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Sample records for truncated kdr gene

  1. Identification of an alternative knockdown resistance (kdr)-like mutation, M918L, and a novel mutation, V1010A, in the Thrips tabaci voltage-gated sodium channel gene.

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    Wu, Meixiang; Gotoh, Hiroki; Waters, Timothy; Walsh, Douglas B; Lavine, Laura Corley

    2014-06-01

    Knockdown resistance (kdr) has been identified as a main mechanism against pyrethroid insecticides in many arthropod pests including in the onion thrips, Thrips tabaci. To characterize and identify pyrethroid-resistance in onion thrips in Washington state, we conducted insecticide bioassays and sequenced a region of the voltage gated sodium channel gene from several different T. tabaci populations. Field collected Thrips tabaci were found to have large variations in resistance to the pyrethroid insecticide lambda-cyhalothrin. We identified two single nucleotide substitutions in our analysis of a partial sequence of the T. tabaci voltage-gated sodium channel gene. One mutation resulted in the non-synonymous substitution of methionine with leucine (M918L), which is well known to be responsible for super knockdown resistance in some pest species. Another non-synonymous substitution, a valine (GTT) to alanine (GCT) replacement at amino acid 1010 (V1010A) was identified in our study and was associated with lambda-cyhalothrin resistance. We have characterized a known kdr mutation and identified a novel mutation in the voltage-gated sodium channel gene of Thrips tabaci associated with resistance to lambda-cyhalothrin. This gene region and these mutations are expected to be useful in the development of a diagnostic test to detect kdr resistance in many onion thrips populations. © 2013 Society of Chemical Industry.

  2. Diversity and frequency of kdr mutations within Anopheles sinensis populations from Guangxi, China.

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    Yang, Chan; Feng, Xiangyang; Huang, Zushi; Li, Mei; Qiu, Xinghui

    2016-08-15

    Anopheles sinensis is a major vector of malaria in China and its control is under great threat as the development of insecticide resistance. Voltage-gated sodium channel (VGSC) is the target of several classes of insecticides. Genetic mutations of VGSC have been documented to confer knockdown resistance (kdr) to dichlorodiphenyltrichloroethane (DDT) and pyrethroids in mosquitoes. To control this vector efficiently, it is important to know the resistance-associated genetic mutations, their distribution frequencies and genealogical relations. Three hundreds and thirteen (313) adults of An. sinensis collected from nine locations across Guangxi Zhuang Autonomous Region were used. The partial sequence of the An. sinensis voltage gated sodium channel gene (AS-VGSC) containing codon 1014 was sequenced. PHASE2.1 was used to construct the haplotypes of each individual, and the accuracy of haplotypes was further confirmed by clone sequencing. The genealogical relations of kdr mutations in AS-VGSC was analysed using TCS 2.1 and Network 5.0. Sixteen AS-VGSC haplotypes including seven haplotypes carrying non-synonymous mutations at codon 1014, and fifty-five AS-VGSC genotypes were identified from 313 mosquitoes collected from nine geographical locations across Guangxi. The number of haplotypes in each of the nine populations ranged from 5 to 13. The frequency of haplotypes carrying kdr mutations ranged from 2.7 to 80.0 % within the nine populations, of which 1014C was unexpectedly high in the northeast of Guangxi. Genealogical analysis suggested multiple origins of kdr mutations in An. sinensis. Diverse haplotypes of AS-VGSC are distributed in Guangxi. The presence of haplotypes carrying mutations at codon 1014 indicates a risk of pyrethroid and DDT resistance. The kdr mutations show differential distribution geographically, with high frequencies occurred in the northeast of Guangxi. Genealogical analysis suggests multiple origins of kdr mutations in An. sinensis populations

  3. Knockdown resistance (kdr) of the voltage-gated sodium channel gene of Aedes aegypti population in Denpasar, Bali, Indonesia.

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    Hamid, Penny Humaidah; Prastowo, Joko; Widyasari, Anis; Taubert, Anja; Hermosilla, Carlos

    2017-06-05

    Aedes aegypti is the main vector of several arthropod-borne viral infections in the tropics profoundly affecting humans, such as dengue fever (DF), West Nile (WN), chikungunya and more recently Zika. Eradication of Aedes still largely depends on insecticides, which is the most cost-effective strategy, and often inefficient due to resistance development in exposed Aedes populations. We here conducted a study of Ae. aegypti resistance towards several insecticides regularly used in the city of Denpasar, Bali, Indonesia. Aedes aegypti egg samples were collected with ovitraps and thereafter hatched in the insectary of the Gadjah Mada University. The F0 generation was used for all bioassay-related experiments and knockdown resistance (kdr) assays. Results clearly showed resistance development of Ae. aegypti against tested insecticides. Mortalities of Ae. aegypti were less than 90% with highest resistance observed against 0.75% permethrin. Mosquitoes from the southern parts of Denpasar presented high level of resistance pattern in comparison to those from the western and northern parts of Denpasar. Kdr analysis of voltage-gated sodium channel (Vgsc) gene showed significant association to S989P and V1016G mutations linked to resistance phenotypes against 0.75% permethrin. Conversely, Ae. aegypti F1534C gene mutation did not result in any significant correlation to resistance development. Periodically surveillance of insecticide resistances in Ae. aegypti mosquitoes will help local public health authorities to set better goals and allow proper evaluation of on-going mosquito control strategies. Initial detection of insecticide resistance will contribute to conduct proper actions in delaying mosquito resistance development such as insecticide rotation or combination of compounds in order to prolong chemical efficacy in combating Ae. aegypti vectors in Indonesia.

  4. PCR-based methods for the detection of L1014 kdr mutation in Anopheles culicifacies sensu lato

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    Singh, Om P; Bali, Prerna; Hemingway, Janet; Subbarao, Sarala K; Dash, Aditya P; Adak, Tridibes

    2009-01-01

    Background Anopheles culicifacies s.l., a major malaria vector in India, has developed widespread resistance to DDT and is becoming resistant to pyrethroids–the only insecticide class recommended for the impregnation of bed nets. Knock-down resistance due to a point mutation in the voltage gated sodium channel at L1014 residue (kdr) is a common mechanism of resistance to DDT and pyrethroids. The selection of this resistance may pose a serious threat to the success of the pyrethroid-impregnated bed net programme. This study reports the presence of kdr mutation (L1014F) in a field population of An. culicifacies s.l. and three new PCR-based methods for kdr genotyping. Methods The IIS4-IIS5 linker to IIS6 segments of the para type voltage gated sodium channel gene of DDT and pyrethroid resistant An. culicifacies s.l. population from the Surat district of India was sequenced. This revealed the presence of an A-to-T substitution at position 1014 leading to a leucine-phenylalanine mutation (L1014F) in a few individuals. Three molecular methods viz. Allele Specific PCR (AS-PCR), an Amplification Refractory Mutation System (ARMS) and Primer Introduced Restriction Analysis-PCR (PIRA-PCR) were developed and tested for kdr genotyping. The specificity of the three assays was validated following DNA sequencing of the samples genotyped. Results The genotyping of this An. culicifacies s.l. population by the three PCR based assays provided consistent result and were in agreement with DNA sequencing result. A low frequency of the kdr allele mostly in heterozygous condition was observed in the resistant population. Frequencies of the different genotypes were in Hardy-Weinberg equilibrium. Conclusion The Leu-Phe mutation, which generates the kdr phenotype in many insects, was detected in a pyrethroid and DDT resistant An. culicifacies s.l. population. Three PCR-based methods were developed for kdr genotyping. All the three assays were specific. The ARMS method was refractory to non

  5. PCR-based methods for the detection of L1014 kdr mutation in Anopheles culicifacies sensu lato

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    Dash Aditya P

    2009-07-01

    Full Text Available Abstract Background Anopheles culicifacies s.l., a major malaria vector in India, has developed widespread resistance to DDT and is becoming resistant to pyrethroids–the only insecticide class recommended for the impregnation of bed nets. Knock-down resistance due to a point mutation in the voltage gated sodium channel at L1014 residue (kdr is a common mechanism of resistance to DDT and pyrethroids. The selection of this resistance may pose a serious threat to the success of the pyrethroid-impregnated bed net programme. This study reports the presence of kdr mutation (L1014F in a field population of An. culicifacies s.l. and three new PCR-based methods for kdr genotyping. Methods The IIS4-IIS5 linker to IIS6 segments of the para type voltage gated sodium channel gene of DDT and pyrethroid resistant An. culicifacies s.l. population from the Surat district of India was sequenced. This revealed the presence of an A-to-T substitution at position 1014 leading to a leucine-phenylalanine mutation (L1014F in a few individuals. Three molecular methods viz. Allele Specific PCR (AS-PCR, an Amplification Refractory Mutation System (ARMS and Primer Introduced Restriction Analysis-PCR (PIRA-PCR were developed and tested for kdr genotyping. The specificity of the three assays was validated following DNA sequencing of the samples genotyped. Results The genotyping of this An. culicifacies s.l. population by the three PCR based assays provided consistent result and were in agreement with DNA sequencing result. A low frequency of the kdr allele mostly in heterozygous condition was observed in the resistant population. Frequencies of the different genotypes were in Hardy-Weinberg equilibrium. Conclusion The Leu-Phe mutation, which generates the kdr phenotype in many insects, was detected in a pyrethroid and DDT resistant An. culicifacies s.l. population. Three PCR-based methods were developed for kdr genotyping. All the three assays were specific. The ARMS method

  6. Assessing the effects of Aedes aegypti kdr mutations on pyrethroid resistance and its fitness cost.

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    Luiz Paulo Brito

    Full Text Available Pyrethroids are the most used insecticide class worldwide. They target the voltage gated sodium channel (NaV, inducing the knockdown effect. In Aedes aegypti, the main dengue vector, the AaNaV substitutions Val1016Ile and Phe1534Cys are the most important knockdown resistance (kdr mutations. We evaluated the fitness cost of these kdr mutations related to distinct aspects of development and reproduction, in the absence of any other major resistance mechanism. To accomplish this, we initially set up 68 crosses with mosquitoes from a natural population. Allele-specific PCR revealed that one couple, the one originating the CIT-32 strain, had both parents homozygous for both kdr mutations. However, this pyrethroid resistant strain also presented high levels of detoxifying enzymes, which synergistically account for resistance, as revealed by biological and biochemical assays. Therefore, we carried out backcrosses between CIT-32 and Rockefeller (an insecticide susceptible strain for eight generations in order to bring the kdr mutation into a susceptible genetic background. This new strain, named Rock-kdr, was highly resistant to pyrethroid and presented reduced alteration of detoxifying activity. Fitness of the Rock-kdr was then evaluated in comparison with Rockefeller. In this strain, larval development took longer, adults had an increased locomotor activity, fewer females laid eggs, and produced a lower number of eggs. Under an inter-strain competition scenario, the Rock-kdr larvae developed even slower. Moreover, when Rockefeller and Rock-kdr were reared together in population cage experiments during 15 generations in absence of insecticide, the mutant allele decreased in frequency. These results strongly suggest that the Ae. aegypti kdr mutations have a high fitness cost. Therefore, enhanced surveillance for resistance should be priority in localities where the kdr mutation is found before new adaptive alleles can be selected for diminishing the

  7. VEGF and VEGFR-2 (KDR) internalization is required for endothelial recovery during wound healing

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    Constantino Rosa Santos, Susana; Miguel, Claudia; Domingues, Ines; Calado, Angelo; Zhu Zhenping; Wu Yan; Dias, Sergio

    2007-01-01

    Vascular endothelial growth factor (VEGF) receptor activation regulates endothelial cell (EC) survival, migration and proliferation. Recently, it was suggested the cross-talk between the VEGF receptors-1 (FLT-1) and -2 (KDR) modulated several of these functions, but the detailed molecular basis for such interactions remained unexplained. Here we demonstrate for the first time that VEGF stimulation of EC monolayers induced a rapid FLT-1-mediated internalization of KDR to the nucleus, via microtubules and the endocytic pathway, internalization which required the activation of PI 3-kinase/AKT. KDR deletion mutants were generated in several tyrosine residues; in these, VEGF-induced KDR internalization was impaired, demonstrating this process required activation (phosphorylation) of the receptor. Furthermore, we demonstrate that in vitro wounding of EC monolayers leads to a rapid and transient internalization of VEGF + KDR to the nucleus, which is essential for monolayer recovery. Notably, FLT-1 blockade impedes VEGF and KDR activation and internalization, blocking endothelial monolayer recovery. Our data reveal a previously unrecognized mechanism induced by VEGF on EC, which regulates EC recovery following wounding, and as such indicate novel targets for therapeutic intervention

  8. First report of L1014F-kdr mutation in Culex pipiens complex from Morocco.

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    Bkhache, Meriem; Tmimi, Fatim-Zohra; Charafeddine, Omar; Faraj, Chafika; Failloux, Anna-Bella; Sarih, M'hammed

    2016-12-16

    Mosquitoes of the Culex pipiens complex, competent vectors for West Nile virus (WNV) and Rift Valley fever virus (RVFV) are widely targeted by insecticide treatments. The intensive application of chemical insecticides led to the development of resistance in many insects including Culex pipiens mosquitoes. The absence of data on resistance mechanisms in Morocco allow us to assess the levels of lambda-cyhalothrin resistance and the frequency of the mutated gene L1014F kdr in different forms of Cx. pipiens complex from three regions of Morocco. Mosquito adults were reared from immature stages collected in three different regions in Morocco (Tangier, Casablanca and Marrakech). Standard WHO insecticide susceptibility tests were conducted on adults emerged from collected larvae. Specimens were identified as belonging to the Culex pipiens complex using a multiplex PCR assay with diagnostic primers designed from the flanking region of microsatellite CQ11. Identified mosquitoes were then tested for the presence of the L1014F kdr mutation using PCR assay. Our results showed that 21% of the tested population has a resistance to lambda-cyhalothrin. The molecular identification of survivors shows that 43% belonged to the Cx. pipiens pipiens and only 9.5% to the Cx. pipiens molestus form. On the other hand, 416 specimens were screened for the L1014F kdr mutation. L1014F mutation was detected in different forms of Cx. pipiens in different sites. The frequency of L1014F mutation was similar between the Cx. pipiens pipiens form and hybrid form, while it was lower in the Cx. pipiens molestus form. The presence of the L1014F kdr allele was significantly associated with resistance to lambda-cyhalothrin in Cx. pipiens pipiens (P Morocco. These findings will provide important information to propose more adapted vector control measures towards this mosquito species, potential vector of arboviruses.

  9. Development of an allele-specific, loop-mediated, isothermal amplification method (AS-LAMP to detect the L1014F kdr-w mutation in Anopheles gambiae s. l.

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    Badolo Athanase

    2012-07-01

    Full Text Available Abstract Background Malaria control relies heavily on treated bed nets and indoor residual spraying with pyrethroid insecticides. Unfortunately, the resistance to pyrethroid insecticides, mainly due to the kdr mutation, is spreading in the main malaria vector Anopheles gambiae s.l., decreasing the insecticides’ efficacy. To manage the insecticide resistance rapidly and flexibly, simple and effective tools for the early detection of resistant mosquitoes are needed. This study aimed to develop an allele-specific, loop-mediated, isothermal amplification (AS-LAMP method to detect the West African-type kdr mutation (kdr-w; L1014F in field-collected mosquitoes. Methods DNA fragments of the wild-type and the mutated kdr gene were used to select the primers and develop the method. The primers were designed with the mutation at the 5’ end of the backward inner primer (BIP. The AS-LAMP method was compared to the AS-PCR method using the genomic DNA of 120 field-collected mosquitoes. Results The AS-LAMP method could discriminate between the wild-type homozygote, the heterozygote, and the kdr-w homozygote within 75 min. The AS-LAMP method has the advantage of being faster and at least as sensitive and specific as the AS-PCR method. Conclusions The AS-LAMP method can be used to detect the kdr mutation for quick decision-making, even in less well-equipped laboratories.

  10. Gene-gene interactions and gene polymorphisms of VEGFA and EG-VEGF gene systems in recurrent pregnancy loss.

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    Su, Mei-Tsz; Lin, Sheng-Hsiang; Chen, Yi-Chi; Kuo, Pao-Lin

    2014-06-01

    Both vascular endothelial growth factor A (VEGFA) and endocrine gland-derived vascular endothelial growth factor (EG-VEGF) systems play major roles in angiogenesis. A body of evidence suggests VEGFs regulate critical processes during pregnancy and have been associated with recurrent pregnancy loss (RPL). However, little information is available regarding the interaction of these two major major angiogenesis-related systems in early human pregnancy. This study was conducted to investigate the association of gene polymorphisms and gene-gene interaction among genes in VEGFA and EG-VEGF systems and idiopathic RPL. A total of 98 women with history of idiopathic RPL and 142 controls were included, and 5 functional SNPs selected from VEGFA, KDR, EG-VEGF (PROK1), PROKR1 and PROKR2 were genotyped. We used multifactor dimensionality reduction (MDR) analysis to choose a best model and evaluate gene-gene interactions. Ingenuity pathways analysis (IPA) was introduced to explore possible complex interactions. Two receptor gene polymorphisms [KDR (Q472H) and PROKR2 (V331M)] were significantly associated with idiopathic RPL (P<0.01). The MDR test revealed that the KDR (Q472H) polymorphism was the best loci to be associated with RPL (P=0.02). IPA revealed EG-VEGF and VEGFA systems shared several canonical signaling pathways that may contribute to gene-gene interactions, including the Akt, IL-8, EGFR, MAPK, SRC, VHL, HIF-1A and STAT3 signaling pathways. Two receptor gene polymorphisms [KDR (Q472H) and PROKR2 (V331M)] were significantly associated with idiopathic RPL. EG-VEGF and VEGFA systems shared several canonical signaling pathways that may contribute to gene-gene interactions, including the Akt, IL-8, EGFR, MAPK, SRC, VHL, HIF-1A and STAT3.

  11. Interleukin-6 triggers human cerebral endothelial cells proliferation and migration: The role for KDR and MMP-9

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    Yao, Jianhua S.; Zhai Wenwu; Young, William L.; Yang Guoyuan

    2006-01-01

    Interleukin-6 (IL-6) is involved in angiogenesis. However, the underlying mechanisms are unknown. Using human cerebral endothelial cell (HCEC), we report for First time that IL-6 triggers HCEC proliferation and migration in a dose-dependent manner, specifically associated with enhancement of VEGF expression, up-regulated and phosphorylated VEGF receptor-2 (KDR), and stimulated MMP-9 secretion. We investigated the signal pathway of IL-6/IL-6R responsible for KDR's regulation. Pharmacological inhibitor of PI3K failed to inhibit IL-6-mediated VEGF overexpression, while blocking ERK1/2 with PD98059 could abolish IL-6-induced KDR overexpression. Further, neutralizing endogenous VEGF attenuated KDR expression and phosphorylation, suggesting that IL-6-induced KDR activation is independent of VEGF stimulation. MMP-9 inhibitor GM6001 significantly decreases HCEC proliferation and migration (p < 0.05), indicating the crucial function of MMP-9 in promoting angiogenic changes in HCECs. We conclude that IL-6 triggers VEGF-induced angiogenic activity through increasing VEGF release, up-regulates KDR expression and phosphorylation through activating ERK1/2 signaling, and stimulates MMP-9 overexpression

  12. Knockdown resistance (kdr)-like mutations in the voltage-gated sodium channel of a malaria vector Anopheles stephensi and PCR assays for their detection.

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    Singh, Om P; Dykes, Cherry L; Lather, Manila; Agrawal, Om P; Adak, Tridibes

    2011-03-14

    Knockdown resistance (kdr) in insects, resulting from mutation(s) in the voltage-gated sodium channel (vgsc) gene is one of the mechanisms of resistance against DDT and pyrethroid-group of insecticides. The most common mutation(s) associated with knockdown resistance in insects, including anophelines, has been reported to be present at residue Leu1014 in the IIS6 transmembrane segment of the vgsc gene. This study reports the presence of two alternative kdr-like mutations, L1014S and L1014F, at this residue in a major malaria vector Anopheles stephensi and describes new PCR assays for their detection. Part of the vgsc (IIS4-S5 linker-to-IIS6 transmembrane segment) of An. stephensi collected from Alwar (Rajasthan, India) was PCR-amplified from genomic DNA, sequenced and analysed for the presence of deduced amino acid substitution(s). Analysis of DNA sequences revealed the presence of two alternative non-synonymous point mutations at L1014 residue in the IIS6 transmembrane segment of vgsc, i.e., T>C mutation on the second position and A>T mutation on the third position of the codon, leading to Leu (TTA)-to-Ser (TCA) and -Phe (TTT) amino acid substitutions, respectively. Polymerase chain reaction (PCR) assays were developed for identification of each of these two point mutations. Genotyping of An. stephensi mosquitoes from Alwar by PCR assays revealed the presence of both mutations, with a high frequency of L1014S. The PCR assays developed for detection of the kdr mutations were specific as confirmed by DNA sequencing of PCR-genotyped samples. Two alternative kdr-like mutations, L1014S and L1014F, were detected in An. stephensi with a high allelic frequency of L1014S. The occurrence of L1014S is being reported for the first time in An. stephensi. Two specific PCR assays were developed for detection of two kdr-like mutations in An. stephensi.

  13. Identification of target genes for wild type and truncated HMGA2 in mesenchymal stem-like cells

    DEFF Research Database (Denmark)

    Henriksen, Jørn Mølgaard; Stabell, Marianne; Meza-Zepeda, Leonardo A

    2010-01-01

    The HMGA2 gene, coding for an architectural transcription factor involved in mesenchymal embryogenesis, is frequently deranged by translocation and/or amplification in mesenchymal tumours, generally leading to over-expression of shortened transcripts and a truncated protein.......The HMGA2 gene, coding for an architectural transcription factor involved in mesenchymal embryogenesis, is frequently deranged by translocation and/or amplification in mesenchymal tumours, generally leading to over-expression of shortened transcripts and a truncated protein....

  14. The Most Developmentally Truncated Fishes Show Extensive Hox Gene Loss and Miniaturized Genomes

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    Malmstrøm, Martin; Britz, Ralf; Matschiner, Michael; Tørresen, Ole K; Hadiaty, Renny Kurnia; Yaakob, Norsham; Tan, Heok Hui; Jakobsen, Kjetill Sigurd; Salzburger, Walter; Rüber, Lukas

    2018-01-01

    Abstract The world’s smallest fishes belong to the genus Paedocypris. These miniature fishes are endemic to an extreme habitat: the peat swamp forests in Southeast Asia, characterized by highly acidic blackwater. This threatened habitat is home to a large array of fishes, including a number of miniaturized but also developmentally truncated species. Especially the genus Paedocypris is characterized by profound, organism-wide developmental truncation, resulting in sexually mature individuals of <8 mm in length with a larval phenotype. Here, we report on evolutionary simplification in the genomes of two species of the dwarf minnow genus Paedocypris using whole-genome sequencing. The two species feature unprecedented Hox gene loss and genome reduction in association with their massive developmental truncation. We also show how other genes involved in the development of musculature, nervous system, and skeleton have been lost in Paedocypris, mirroring its highly progenetic phenotype. Further, our analyses suggest two mechanisms responsible for the genome streamlining in Paedocypris in relation to other Cypriniformes: severe intron shortening and reduced repeat content. As the first report on the genomic sequence of a vertebrate species with organism-wide developmental truncation, the results of our work enhance our understanding of genome evolution and how genotypes are translated to phenotypes. In addition, as a naturally simplified system closely related to zebrafish, Paedocypris provides novel insights into vertebrate development. PMID:29684203

  15. The Most Developmentally Truncated Fishes Show Extensive Hox Gene Loss and Miniaturized Genomes.

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    Malmstrøm, Martin; Britz, Ralf; Matschiner, Michael; Tørresen, Ole K; Hadiaty, Renny Kurnia; Yaakob, Norsham; Tan, Heok Hui; Jakobsen, Kjetill Sigurd; Salzburger, Walter; Rüber, Lukas

    2018-04-01

    The world's smallest fishes belong to the genus Paedocypris. These miniature fishes are endemic to an extreme habitat: the peat swamp forests in Southeast Asia, characterized by highly acidic blackwater. This threatened habitat is home to a large array of fishes, including a number of miniaturized but also developmentally truncated species. Especially the genus Paedocypris is characterized by profound, organism-wide developmental truncation, resulting in sexually mature individuals of <8 mm in length with a larval phenotype. Here, we report on evolutionary simplification in the genomes of two species of the dwarf minnow genus Paedocypris using whole-genome sequencing. The two species feature unprecedented Hox gene loss and genome reduction in association with their massive developmental truncation. We also show how other genes involved in the development of musculature, nervous system, and skeleton have been lost in Paedocypris, mirroring its highly progenetic phenotype. Further, our analyses suggest two mechanisms responsible for the genome streamlining in Paedocypris in relation to other Cypriniformes: severe intron shortening and reduced repeat content. As the first report on the genomic sequence of a vertebrate species with organism-wide developmental truncation, the results of our work enhance our understanding of genome evolution and how genotypes are translated to phenotypes. In addition, as a naturally simplified system closely related to zebrafish, Paedocypris provides novel insights into vertebrate development.

  16. Double suicide genes selectively kill human umbilical vein endothelial cells

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    Liu Lunxu

    2011-02-01

    Full Text Available Abstract Background To construct a recombinant adenovirus containing CDglyTK double suicide genes and evaluate the killing effect of the double suicide genes driven by kinase domain insert containing receptor (KDR promoter on human umbilical vein endothelial cells. Methods Human KDR promoter, Escherichia coli (E. coli cytosine deaminase (CD gene and the herpes simplex virus-thymidine kinase (TK gene were cloned using polymerase chain reaction (PCR. Plasmid pKDR-CDglyTK was constructed with the KDR promoter and CDglyTK genes. A recombinant adenoviral plasmid AdKDR-CDglyTK was then constructed and transfected into 293 packaging cells to grow and harvest adenoviruses. KDR-expressing human umbilical vein endothelial cells (ECV304 and KDR-negative liver cancer cell line (HepG2 were infected with the recombinant adenoviruses at different multiplicity of infection (MOI. The infection rate was measured by green fluorescent protein (GFP expression. The infected cells were cultured in culture media containing different concentrations of prodrugs ganciclovir (GCV and/or 5-fluorocytosine (5-FC. The killing effects were measured using two different methods, i.e. annexin V-FITC staining and terminal transferase-mediated dUTP nick end-labeling (TUNEL staining. Results Recombinant adenoviruses AdKDR-CDglyTK were successfully constructed and they infected ECV304 and HepG2 cells efficiently. The infection rate was dependent on MOI of recombinant adenoviruses. ECV304 cells infected with AdKDR-CDglyTK were highly sensitive to GCV and 5-FC. The cell survival rate was dependent on both the concentration of the prodrugs and the MOI of recombinant adenoviruses. In contrast, there were no killing effects in the HepG2 cells. The combination of two prodrugs was much more effective in killing ECV304 cells than GCV or 5-FC alone. The growth of transgenic ECV304 cells was suppressed in the presence of prodrugs. Conclusion AdKDR-CDglyTK/double prodrog system may be a useful

  17. Investigating knockdown resistance (kdr) mechanism against pyrethroids/DDT in the malaria vector Anopheles funestus across Africa.

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    Irving, Helen; Wondji, Charles S

    2017-08-09

    Understanding the molecular basis of insecticide resistance is key to improve the surveillance and monitoring of malaria vector populations under control. In the major malaria vector Anopheles funestus, little is currently known about the role of the knockdown resistance (kdr) mechanism. Here, we investigated the presence and contribution of knockdown resistance (kdr) to pyrethroids/DDT resistance observed in Anopheles funestus across Africa. Pyrosequencing genotyping and sequencing of the voltage gated sodium channel (VGSC) gene did not detect the common L1014F mutation in field collected An. funestus across Africa. Amplification and cloning of the full-length of the sodium channel gene in pyrethroid resistant mosquitoes revealed evidences of alternative splicing events with three transcripts of 2092, 2061 and 2117 amino acids (93% average similarity to An. gambiae). Several amino acid changes were detected close to the domain II of the protein such as L928R, F938 W, I939S, L802S and T1008 M. However, all these mutations are found at low frequency and their role in pyrethroid resistance could not be established. The presence of the exclusive alternative splicing at exon 19 was not associated with resistance phenotype. Analysis of patterns of genetic diversity of the VGSC gene revealed a high polymorphism level of this gene across Africa with no evidence of directional selection suggesting a limited role for knockdown resistance in pyrethroid resistance in An. funestus. Patterns of genetic differentiation correlate with previous observations of the existence of barriers to gene flow Africa-wide with southern population significantly differentiated from other regions. Despite an apparent limited role of knockdown resistance in An. funestus, it is necessary to continue to monitor the contribution of the mutations detected here as increasing selection from insecticide-based interventions may change the dynamic in field populations as previously observed in other

  18. Glycoprotein gene truncation in avian metapneumovirus subtype C isolates from the United States.

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    Velayudhan, Binu T; Yu, Qingzhong; Estevez, Carlos N; Nagaraja, Kakambi V; Halvorson, David A

    2008-10-01

    The length of the published glycoprotein (G) gene sequences of avian metapneumovirus subtype-C (aMPV-C) isolated from domestic turkeys and wild birds in the United States (1996-2003) remains controversial. To explore the G gene size variation in aMPV-C by the year of isolation and cell culture passage levels, we examined 21 turkey isolates of aMPV-C at different cell culture passages. The early domestic turkey isolates of aMPV-C (aMPV/CO/1996, aMPV/MN/1a-b, and 2a-b/97) had a G gene of 1,798 nucleotides (nt) that coded for a predicted protein of 585 amino acids (aa) and showed >97% nt similarity with that of aMPV-C isolated from Canada geese. This large G gene got truncated upon serial passages in Vero cell cultures by deletion of 1,015 nt near the end of the open reading frame. The recent domestic turkey isolates of aMPV-C lacked the large G gene but instead had a small G gene of 783 nt, irrespective of cell culture passage levels. In some cultures, both large and small genes were detected, indicating the existence of a mixed population of the virus. Apparently, serial passage of aMPV-C in cell cultures and natural passage in turkeys in the field led to truncation of the G gene, which may be a mechanism of virus evolution for survival in a new host or environment.

  19. The role of VEGF and KDR polymorphisms in moyamoya disease and collateral revascularization.

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    Young Seok Park

    Full Text Available We conducted a case-control study to investigate whether vascular endothelial growth factor (VEGF -2578, -1154, -634, and 936 and kinase insert domain containing receptor (KDR -604, 1192, and 1719 polymorphisms are associated with moyamoya disease. Korean patients with moyamoya disease (n = 107, mean age, 20.9±15.9 years; 66.4% female and 243 healthy control subjects (mean age, 23.0±16.1 years; 56.8% female were included. The subjects were divided into pediatric and adult groups. Among the 64 surgical patients, we evaluated collateral vessel formation after 2 years and divided patients into good (collateral grade A or poor (collateral grade B and C groups. The frequencies and distributions of four VEGF (-2578, -1154, -634, and 936 and KDR (-604, 1192, and 1719 polymorphisms were assessed from patients with moyamoya disease and compared to the control group. No differences were observed in VEGF -2578, -1154, -634, and 936 or KDR -604, 1192, and 1719 polymorphisms between the control group and moyamoya disease group. However, we found the -634CC genotype occurred less frequently in the pediatric moyamoya group (p = 0.040 whereas the KDR -604C/1192A/1719T haplotype increased the risk of pediatric moyamoya (p = 0.024. Patients with the CC genotype of VEGF -634 had better collateral vessel formation after surgery. Our results suggest that the VEGF -634G allele is associated with pediatric moyamoya disease and poor collateral vessel formation.

  20. The -271 G>A polymorphism of kinase insert domain-containing receptor gene regulates its transcription level in patients with non-small cell lung cancer

    International Nuclear Information System (INIS)

    An, She-Juan; Chen, Zhi-Hong; Lin, Qiu-Xiong; Su, Jian; Chen, Hua-Jun; Lin, Jia-Ying; Wu, Yi-Long

    2009-01-01

    Kinase insert domain-containing receptor (KDR) plays a critical role in the metastasis of cancer and is used as a molecular target in cancer therapy. We investigated the characteristics of the -271 G>A polymorphism of the KDR gene to gain information that may benefit the development of individualized therapies for patients with non-small cell lung cancer (NSCLC). The -271 G>A polymorphism of the KDR gene in 106 lung cancer patients and 203 healthy control individuals was analyzed by polymerase chain reaction (PCR) and DNA sequencing methods. Real-time quantitative PCR and immunohistochemical methods were used to evaluate KDR mRNA and protein expression levels, respectively, in frozen tumor specimens. The -271 G>A polymorphism was associated with the mRNA expression level of the KDR gene in tumor tissues (t = 2.178, P = 0.032, independent samples t-test). Compared with the AG/GG genotype, the AA genotype was associated with higher KDR mRNA expression in tumor tissues. We found no relationship between the genotype and the KDR protein expression level and no significant difference in the distribution of the KDR gene polymorphism genotypes between lung cancer patients and the control group (χ 2 = 1.269, P = 0.264, Fisher's exact test). This study is the first to show that the -271 G>A polymorphism of the KDR gene may be a functional polymorphism related to the regulation of gene transcription. These findings may have important implications for therapies targeting KDR in patients with NSCLC

  1. A simplified high-throughput method for pyrethroid knock-down resistance (kdr) detection in Anopheles gambiae

    Science.gov (United States)

    Lynd, Amy; Ranson, Hilary; McCall, P J; Randle, Nadine P; Black, William C; Walker, Edward D; Donnelly, Martin J

    2005-01-01

    Background A single base pair mutation in the sodium channel confers knock-down resistance to pyrethroids in many insect species. Its occurrence in Anopheles mosquitoes may have important implications for malaria vector control especially considering the current trend for large scale pyrethroid-treated bednet programmes. Screening Anopheles gambiae populations for the kdr mutation has become one of the mainstays of programmes that monitor the development of insecticide resistance. The screening is commonly performed using a multiplex Polymerase Chain Reaction (PCR) which, since it is reliant on a single nucleotide polymorphism, can be unreliable. Here we present a reliable and potentially high throughput method for screening An. gambiae for the kdr mutation. Methods A Hot Ligation Oligonucleotide Assay (HOLA) was developed to detect both the East and West African kdr alleles in the homozygous and heterozygous states, and was optimized for use in low-tech developing world laboratories. Results from the HOLA were compared to results from the multiplex PCR for field and laboratory mosquito specimens to provide verification of the robustness and sensitivity of the technique. Results and Discussion The HOLA assay, developed for detection of the kdr mutation, gives a bright blue colouration for a positive result whilst negative reactions remain colourless. The results are apparent within a few minutes of adding the final substrate and can be scored by eye. Heterozygotes are scored when a sample gives a positive reaction to the susceptible probe and the kdr probe. The technique uses only basic laboratory equipment and skills and can be carried out by anyone familiar with the Enzyme-linked immunosorbent assay (ELISA) technique. A comparison to the multiplex PCR method showed that the HOLA assay was more reliable, and scoring of the plates was less ambiguous. Conclusion The method is capable of detecting both the East and West African kdr alleles in the homozygous and

  2. A simplified high-throughput method for pyrethroid knock-down resistance (kdr detection in Anopheles gambiae

    Directory of Open Access Journals (Sweden)

    Walker Edward D

    2005-03-01

    Full Text Available Abstract Background A single base pair mutation in the sodium channel confers knock-down resistance to pyrethroids in many insect species. Its occurrence in Anopheles mosquitoes may have important implications for malaria vector control especially considering the current trend for large scale pyrethroid-treated bednet programmes. Screening Anopheles gambiae populations for the kdr mutation has become one of the mainstays of programmes that monitor the development of insecticide resistance. The screening is commonly performed using a multiplex Polymerase Chain Reaction (PCR which, since it is reliant on a single nucleotide polymorphism, can be unreliable. Here we present a reliable and potentially high throughput method for screening An. gambiae for the kdr mutation. Methods A Hot Ligation Oligonucleotide Assay (HOLA was developed to detect both the East and West African kdr alleles in the homozygous and heterozygous states, and was optimized for use in low-tech developing world laboratories. Results from the HOLA were compared to results from the multiplex PCR for field and laboratory mosquito specimens to provide verification of the robustness and sensitivity of the technique. Results and Discussion The HOLA assay, developed for detection of the kdr mutation, gives a bright blue colouration for a positive result whilst negative reactions remain colourless. The results are apparent within a few minutes of adding the final substrate and can be scored by eye. Heterozygotes are scored when a sample gives a positive reaction to the susceptible probe and the kdr probe. The technique uses only basic laboratory equipment and skills and can be carried out by anyone familiar with the Enzyme-linked immunosorbent assay (ELISA technique. A comparison to the multiplex PCR method showed that the HOLA assay was more reliable, and scoring of the plates was less ambiguous. Conclusion The method is capable of detecting both the East and West African kdr alleles

  3. Analysis of CD45- [CD34+/KDR+] endothelial progenitor cells as juvenile protective factors in a rat model of ischemic-hemorrhagic stroke.

    Directory of Open Access Journals (Sweden)

    Julius L Decano

    Full Text Available Identification of juvenile protective factors (JPFs which are altered with age and contribute to adult-onset diseases could identify novel pathways for reversing the effects of age, an accepted non-modifiable risk factor to adult-onset diseases. Since endothelial progenitor cells (EPCs have been observed to be altered in stroke, hypertension and hypercholesterolemia, said EPCs are candidate JPFs for adult-onset stroke. A priori, if EPC aging plays a 'master-switch JPF-role' in stroke pathogenesis, juvenile EPC therapy alone should delay stroke-onset. Using a hypertensive, transgenic-hyperlipidemic rat model of spontaneous ischemic-hemorrhagic stroke, spTg25, we tested the hypothesis that freshly isolated juvenile EPCs are JPFs that can attenuate stroke progression and delay stroke onset.FACS analysis revealed that CD45- [CD34+/KDR+] EPCs decrease with progression to stroke in spTg25 rats, exhibit differential expression of the dual endodthelin-1/VEGFsp receptor (DEspR and undergo differential DEspR-subtype specific changes in number and in vitro angiogenic tube-incorporation. In vivo EPC infusion of male, juvenile non-expanded cd45-[CD34+/KDR+] EPCs into female stroke-prone rats prior to stroke attenuated progression and delayed stroke onset (P<0.003. Detection of Y-chromosome DNA in brain microvessels of EPC-treated female spTg25 rats indicates integration of male EPCs into female rat brain microvessels. Gradient-echo MRI showed delay of ischemic-hemorrhagic lesions in EPC-treated rats. Real-time RT-PCR pathway-specific array-analysis revealed age-associated gene expression changes in CD45-[CD34+/KDR]EPC subtypes, which were accelerated in stroke-prone rats. Pro-angiogenic genes implicated in intimal hyperplasia were increased in stroke-prone rat EPCs (P<0.0001, suggesting a maladaptive endothelial repair system which acts like a double-edged sword repairing while predisposing to age-associated intimal hyperplasia.Altogether, the data

  4. Src Kinase becomes preferentially associated with the VEGFR, KDR/Flk-1, following VEGF stimulation of vascular endothelial cells

    Directory of Open Access Journals (Sweden)

    Wang Jing

    2002-12-01

    Full Text Available Abstract Background The cytoplasmic tyrosine kinase, Src, has been found to play a crucial role in VEGF (vascular endothelial growth factor – dependent vascular permeability involved in angiogenesis. The two main VEGFRs present on vascular endothelial cells are KDR/Flk-1 (kinase insert domain-containing receptor/fetal liver kinase-1 and Flt-1 (Fms-like tyrosine kinase-1. However, to date, it has not been determined which VEGF receptor (VEGFR is involved in binding to and activating Src kinase following VEGF stimulation of the receptors. Results In this report, we demonstrate that Src preferentially associates with KDR/Flk-1 rather than Flt-1 in human umbilical vein endothelial cells (HUVECs, and that VEGF stimulation resulted in an increase of Src activity associated with activated KDR/Flk-1. These findings were determined through immunoprecipitation-kinase experiments and coimmunoprecipitation studies, and were further confirmed by GST-pull-down assays and Far Western studies. However, Fyn and Yes, unlike Src, were found to associate preferentially with Flt-1. Conclusions Thus, Src preferentially associates with KDR/Flk-1, rather than with Flt-1, upon VEGF stimulation in endothelial cells. Our findings further highlight the potential significance of upregulated KDR/Flk-1-associated Src activity in the process of angiogenesis, and help to elucidate more clearly the specific roles and mechanisms involving Src family tyrosine kinase in VEGF-stimulated signal transduction events.

  5. Molecular evolution of pentatricopeptide repeat genes reveals truncation in species lacking an editing target and structural domains under distinct selective pressures

    Directory of Open Access Journals (Sweden)

    Hayes Michael L

    2012-05-01

    Full Text Available Abstract Background Pentatricopeptide repeat (PPR proteins are required for numerous RNA processing events in plant organelles including C-to-U editing, splicing, stabilization, and cleavage. Fifteen PPR proteins are known to be required for RNA editing at 21 sites in Arabidopsis chloroplasts, and belong to the PLS class of PPR proteins. In this study, we investigate the co-evolution of four PPR genes (CRR4, CRR21, CLB19, and OTP82 and their six editing targets in Brassicaceae species. PPR genes are composed of approximately 10 to 20 tandem repeats and each repeat has two α-helical regions, helix A and helix B, that are separated by short coil regions. Each repeat and structural feature was examined to determine the selective pressures on these regions. Results All of the PPR genes examined are under strong negative selection. Multiple independent losses of editing site targets are observed for both CRR21 and OTP82. In several species lacking the known editing target for CRR21, PPR genes are truncated near the 17th PPR repeat. The coding sequences of the truncated CRR21 genes are maintained under strong negative selection; however, the 3’ UTR sequences beyond the truncation site have substantially diverged. Phylogenetic analyses of four PPR genes show that sequences corresponding to helix A are high compared to helix B sequences. Differential evolutionary selection of helix A versus helix B is observed in both plant and mammalian PPR genes. Conclusion PPR genes and their cognate editing sites are mutually constrained in evolution. Editing sites are frequently lost by replacement of an edited C with a genomic T. After the loss of an editing site, the PPR genes are observed with three outcomes: first, few changes are detected in some cases; second, the PPR gene is present as a pseudogene; and third, the PPR gene is present but truncated in the C-terminal region. The retention of truncated forms of CRR21 that are maintained under strong negative

  6. Molecular evolution of pentatricopeptide repeat genes reveals truncation in species lacking an editing target and structural domains under distinct selective pressures.

    Science.gov (United States)

    Hayes, Michael L; Giang, Karolyn; Mulligan, R Michael

    2012-05-14

    Pentatricopeptide repeat (PPR) proteins are required for numerous RNA processing events in plant organelles including C-to-U editing, splicing, stabilization, and cleavage. Fifteen PPR proteins are known to be required for RNA editing at 21 sites in Arabidopsis chloroplasts, and belong to the PLS class of PPR proteins. In this study, we investigate the co-evolution of four PPR genes (CRR4, CRR21, CLB19, and OTP82) and their six editing targets in Brassicaceae species. PPR genes are composed of approximately 10 to 20 tandem repeats and each repeat has two α-helical regions, helix A and helix B, that are separated by short coil regions. Each repeat and structural feature was examined to determine the selective pressures on these regions. All of the PPR genes examined are under strong negative selection. Multiple independent losses of editing site targets are observed for both CRR21 and OTP82. In several species lacking the known editing target for CRR21, PPR genes are truncated near the 17th PPR repeat. The coding sequences of the truncated CRR21 genes are maintained under strong negative selection; however, the 3' UTR sequences beyond the truncation site have substantially diverged. Phylogenetic analyses of four PPR genes show that sequences corresponding to helix A are high compared to helix B sequences. Differential evolutionary selection of helix A versus helix B is observed in both plant and mammalian PPR genes. PPR genes and their cognate editing sites are mutually constrained in evolution. Editing sites are frequently lost by replacement of an edited C with a genomic T. After the loss of an editing site, the PPR genes are observed with three outcomes: first, few changes are detected in some cases; second, the PPR gene is present as a pseudogene; and third, the PPR gene is present but truncated in the C-terminal region. The retention of truncated forms of CRR21 that are maintained under strong negative selection even in the absence of an editing site target

  7. The combination of heteroduplex analysis and protein truncation test for exact detection of the APC gene mutations

    International Nuclear Information System (INIS)

    Tomka, M.; Kirchhoff, T.; Stefurkova, V.; Zajac, V.; Kulcsar, L.

    1998-01-01

    Familial adenomatous polyposis (FAP) is usually associated with mutation in the adenomatous polyposis coli (APC) gene. To examine the occurrence of these mutations in the number of FAP suspected families from the whole Slovakia effectively, we have applied heteroduplex analysis (HDA) and protein truncation test (PTT) for the analyses of 2-5 base pair deletions and point mutations of the APC gene. In the analyzed exon 15 of the APC gene determined by the primers 15Efor-15Grev for HDA and 15ET7-15J3 for PTT more than 70% of mutations should be deletions [3, 12], which are detectable by HDA. In our collection of 5 FAP families mutations in the APC gene were found in families 10, 27 and 41 using HDA. By PTT test the formation of truncated APC protein in FAP families 2, 10, 16 and 27 were revealed. The necessity of combination of at least HDA and PTT techniques for exact detection of APC mutations in analyzed APC region is discussed. (authors)

  8. Expression of a truncated Hmga1b gene induces gigantism, lipomatosis and B-cell lymphomas in mice.

    Science.gov (United States)

    Fedele, Monica; Visone, Rosa; De Martino, Ivana; Palmieri, Dario; Valentino, Teresa; Esposito, Francesco; Klein-Szanto, Andres; Arra, Claudio; Ciarmiello, Andrea; Croce, Carlo M; Fusco, Alfredo

    2011-02-01

    HMGA1 gene rearrangements have been frequently described in human lipomas. In vitro studies suggest that HMGA1 proteins have a negative role in the control of adipocyte cell growth, and that HMGA1 gene truncation acts in a dominant-negative fashion. Therefore, to define better the role of the HMGA1 alterations in the generation of human lipomas, we generated mice carrying an Hmga1b truncated (Hmga1b/T) gene. These mice develop a giant phenotype together with a drastic expansion of the retroperitoneal and subcutaneous white adipose tissue. We show that the activation of the E2F pathway likely accounts, at least in part, for this phenotype. Interestingly, the Hmga1b/T mice also develop B-cell lymphomas similar to that occurring in Hmga1-knockout mice, supporting a dominant-negative role of the Hmga1b/T mutant also in vivo. Copyright © 2010 Elsevier Ltd. All rights reserved.

  9. Contrasting patterns of insecticide resistance and knockdown resistance (kdr) in the dengue vectors Aedes aegypti and Aedes albopictus from Malaysia.

    Science.gov (United States)

    Ishak, Intan H; Jaal, Zairi; Ranson, Hilary; Wondji, Charles S

    2015-03-25

    Knowledge on the extent, distribution and mechanisms of insecticide resistance is essential for successful insecticide-based dengue control interventions. Here, we report an extensive resistance profiling of the dengue vectors Aedes aegypti and Aedes albopictus across Malaysia and establish the contribution of knockdown resistance mechanism revealing significant contrast between both species. Aedes mosquitoes were collected from four states in Malaysia in 2010 using ovitraps and tested against six major insecticides using WHO bioassays. Knockdown resistance (kdr) was investigated in both species. A moderate resistance to temephos was detected from samples collected in 2010 in Penang, Kuala Lumpur, Johor Bharu and Kota Bharu (1.5 Malaysia but neither of these mutations were found in Ae. albopictus. Additionally, signatures of selection were detected on the Voltage-gated sodium channel gene in Ae. aegypti but not in Ae. albopictus. The presence of the 1534C allele was significantly associated with pyrethroid resistance and an additive effect to pyrethroid resistance was observed in individuals containing both kdr alleles. Findings from this study will help to design and implement successful insecticide-based interventions against Ae. aegypti and Ae. albopictus to improve dengue control across Malaysia.

  10. Truncating PREX2 mutations activate its GEF activity and alter gene expression regulation in NRAS-mutant melanoma

    KAUST Repository

    Lissanu Deribe, Yonathan

    2016-03-01

    PREX2 (phosphatidylinositol-3,4,5-triphosphate-dependent Rac-exchange factor 2) is a PTEN (phosphatase and tensin homolog deleted on chromosome 10) binding protein that is significantly mutated in cutaneous melanoma and pancreatic ductal adenocarcinoma. Here, genetic and biochemical analyses were conducted to elucidate the nature and mechanistic basis of PREX2 mutation in melanoma development. By generating an inducible transgenic mouse model we showed an oncogenic role for a truncating PREX2 mutation (PREX2E824*) in vivo in the context of mutant NRAS. Using integrative cross-species gene expression analysis, we identified deregulated cell cycle and cytoskeleton organization as significantly perturbed biological pathways in PREX2 mutant tumors. Mechanistically, truncation of PREX2 activated its Rac1 guanine nucleotide exchange factor activity, abolished binding to PTEN and activated the PI3K (phosphatidyl inositol 3 kinase)/Akt signaling pathway. We further showed that PREX2 truncating mutations or PTEN deletion induces down-regulation of the tumor suppressor and cell cycle regulator CDKN1C (also known as p57KIP2). This down-regulation occurs, at least partially, through DNA hypomethylation of a differentially methylated region in chromosome 11 that is a known regulatory region for expression of the CDKN1C gene. Together, these findings identify PREX2 as a mediator of NRAS-mutant melanoma development that acts through the PI3K/PTEN/Akt pathway to regulate gene expression of a cell cycle regulator.

  11. Truncating PREX2 mutations activate its GEF activity and alter gene expression regulation in NRAS-mutant melanoma.

    Science.gov (United States)

    Lissanu Deribe, Yonathan; Shi, Yanxia; Rai, Kunal; Nezi, Luigi; Amin, Samir B; Wu, Chia-Chin; Akdemir, Kadir C; Mahdavi, Mozhdeh; Peng, Qian; Chang, Qing Edward; Hornigold, Kirsti; Arold, Stefan T; Welch, Heidi C E; Garraway, Levi A; Chin, Lynda

    2016-03-01

    PREX2 (phosphatidylinositol-3,4,5-triphosphate-dependent Rac-exchange factor 2) is a PTEN (phosphatase and tensin homolog deleted on chromosome 10) binding protein that is significantly mutated in cutaneous melanoma and pancreatic ductal adenocarcinoma. Here, genetic and biochemical analyses were conducted to elucidate the nature and mechanistic basis of PREX2 mutation in melanoma development. By generating an inducible transgenic mouse model we showed an oncogenic role for a truncating PREX2 mutation (PREX2(E824)*) in vivo in the context of mutant NRAS. Using integrative cross-species gene expression analysis, we identified deregulated cell cycle and cytoskeleton organization as significantly perturbed biological pathways in PREX2 mutant tumors. Mechanistically, truncation of PREX2 activated its Rac1 guanine nucleotide exchange factor activity, abolished binding to PTEN and activated the PI3K (phosphatidyl inositol 3 kinase)/Akt signaling pathway. We further showed that PREX2 truncating mutations or PTEN deletion induces down-regulation of the tumor suppressor and cell cycle regulator CDKN1C (also known as p57(KIP2)). This down-regulation occurs, at least partially, through DNA hypomethylation of a differentially methylated region in chromosome 11 that is a known regulatory region for expression of the CDKN1C gene. Together, these findings identify PREX2 as a mediator of NRAS-mutant melanoma development that acts through the PI3K/PTEN/Akt pathway to regulate gene expression of a cell cycle regulator.

  12. Truncating PREX2 mutations activate its GEF activity and alter gene expression regulation in NRAS-mutant melanoma

    KAUST Repository

    Lissanu Deribe, Yonathan; Shi, Yanxia; Rai, Kunal; Nezi, Luigi; Amin, Samir B.; Wu, Chia-Chin; Akdemir, Kadir C.; Mahdavi, Mozhdeh; Peng, Qian; Chang, Qing Edward; Hornigold, Kirsti; Arold, Stefan T.; Welch, Heidi C. E.; Garraway, Levi A.; Chin, Lynda

    2016-01-01

    PREX2 (phosphatidylinositol-3,4,5-triphosphate-dependent Rac-exchange factor 2) is a PTEN (phosphatase and tensin homolog deleted on chromosome 10) binding protein that is significantly mutated in cutaneous melanoma and pancreatic ductal adenocarcinoma. Here, genetic and biochemical analyses were conducted to elucidate the nature and mechanistic basis of PREX2 mutation in melanoma development. By generating an inducible transgenic mouse model we showed an oncogenic role for a truncating PREX2 mutation (PREX2E824*) in vivo in the context of mutant NRAS. Using integrative cross-species gene expression analysis, we identified deregulated cell cycle and cytoskeleton organization as significantly perturbed biological pathways in PREX2 mutant tumors. Mechanistically, truncation of PREX2 activated its Rac1 guanine nucleotide exchange factor activity, abolished binding to PTEN and activated the PI3K (phosphatidyl inositol 3 kinase)/Akt signaling pathway. We further showed that PREX2 truncating mutations or PTEN deletion induces down-regulation of the tumor suppressor and cell cycle regulator CDKN1C (also known as p57KIP2). This down-regulation occurs, at least partially, through DNA hypomethylation of a differentially methylated region in chromosome 11 that is a known regulatory region for expression of the CDKN1C gene. Together, these findings identify PREX2 as a mediator of NRAS-mutant melanoma development that acts through the PI3K/PTEN/Akt pathway to regulate gene expression of a cell cycle regulator.

  13. Resistance to DDT and pyrethroids and increased kdr mutation frequency in An. gambiae after the implementation of permethrin-treated nets in Senegal.

    Directory of Open Access Journals (Sweden)

    Mamadou O Ndiath

    Full Text Available The aim of this study was to evaluate the susceptibility to insecticides of An. gambiae mosquitoes sampled in Dielmo (Senegal, in 2010, 2 years after the implementation of Long Lasting Insecticide-treated Nets (LLINs and to report the evolution of kdr mutation frequency from 2006 to 2010.WHO bioassay susceptibility tests to 6 insecticides were performed on adults F0, issuing from immature stages of An. gambiae s.l., sampled in August 2010. Species and molecular forms as well as the presence of L1014F and L1014S kdr mutations were assessed by PCR. Longitudinal study of kdr mutations was performed on adult mosquitoes sampled monthly by night landing catches from 2006 to 2010.No specimen studied presented the L1014S mutation. During the longitudinal study, L1014F allelic frequency rose from 2.4% in year before the implementation of LLINs to 4.6% 0-12 months after and 18.7% 13-30 months after. In 2010, An. gambiae were resistant to DDT, Lambda-cyhalothrin, Deltamethrin and Permethrin (mortality rates ranging from 46 to 63% but highly susceptible to Fenitrothion and Bendiocarb (100% mortality. There was significantly more RR genotype among An. gambiae surviving exposure to DDT or Pyrethroids. An. arabiensis represented 3.7% of the sampled mosquitoes (11/300 with no kdr resistance allele detected. An. gambiae molecular form M represented 29.7% of the mosquitoes with, among them, kdr genotypes SR (18% and SS (82%. An. gambiae molecular form S represented 66% of the population with, among them, kdr genotype SS (33.3%, SR (55.6% and RR (11.1%. Only 2 MS hybrid mosquitoes were sampled and presented SS kdr genotype.Biological evidence of resistance to DDT and pyrethroids was detected among An. gambiae mosquitoes in Dielmo (Senegal within 24 months of community use of LLINs. Molecular identification of L1014F mutation indicated that target site resistance increased after the implementation of LLINs.

  14. Multi-country Survey Revealed Prevalent and Novel F1534S Mutation in Voltage-Gated Sodium Channel (VGSC Gene in Aedes albopictus.

    Directory of Open Access Journals (Sweden)

    Jiabao Xu

    2016-05-01

    Full Text Available Aedes albopictus is an important dengue vector because of its aggressive biting behavior and rapid spread out of its native home range in Southeast Asia. Pyrethroids are widely used for adult mosquito control, and resistance to pyrethroids should be carefully monitored because vector control is the only effective method currently available to prevent dengue transmission. The voltage-gated sodium channel gene is the target site of pyrethroids, and mutations in this gene cause knockdown resistance (kdr. Previous studies reported various mutations in the voltage-gated sodium channel (VGSC gene, but the spatial distribution of kdr mutations in Ae. albopictus has not been systematically examined, and the association between kdr mutation and phenotypic resistance has not been established.A total of 597 Ae. albopictus individuals from 12 populations across Asia, Africa, America and Europe were examined for mutations in the voltage-gated sodium channel gene. Three domains for a total of 1,107 bp were sequenced for every individual. Two populations from southern China were examined for pyrethroid resistance using the World Health Organization standard tube bioassay, and the association between kdr mutations and phenotypic resistance was tested.A total of 29 synonymous mutations were found across domain II, III and IV of the VGSC gene. Non-synonymous mutations in two codons of the VGSC gene were detected in 5 populations from 4 countries. A novel mutation at 1532 codon (I1532T was found in Rome, Italy with a frequency of 19.7%. The second novel mutation at codon 1534 (F1534S was detected in southern China and Florida, USA with a frequency ranging from 9.5-22.6%. The WHO insecticide susceptibility bioassay found 90.1% and 96.1% mortality in the two populations from southern China, suggesting resistance and probable resistance. Positive association between kdr mutations with deltamethrin resistance was established in these two populations.Two novel kdr

  15. Multi-country Survey Revealed Prevalent and Novel F1534S Mutation in Voltage-Gated Sodium Channel (VGSC) Gene in Aedes albopictus.

    Science.gov (United States)

    Xu, Jiabao; Bonizzoni, Mariangela; Zhong, Daibin; Zhou, Guofa; Cai, Songwu; Li, Yiji; Wang, Xiaoming; Lo, Eugenia; Lee, Rebecca; Sheen, Roger; Duan, Jinhua; Yan, Guiyun; Chen, Xiao-Guang

    2016-05-01

    Aedes albopictus is an important dengue vector because of its aggressive biting behavior and rapid spread out of its native home range in Southeast Asia. Pyrethroids are widely used for adult mosquito control, and resistance to pyrethroids should be carefully monitored because vector control is the only effective method currently available to prevent dengue transmission. The voltage-gated sodium channel gene is the target site of pyrethroids, and mutations in this gene cause knockdown resistance (kdr). Previous studies reported various mutations in the voltage-gated sodium channel (VGSC) gene, but the spatial distribution of kdr mutations in Ae. albopictus has not been systematically examined, and the association between kdr mutation and phenotypic resistance has not been established. A total of 597 Ae. albopictus individuals from 12 populations across Asia, Africa, America and Europe were examined for mutations in the voltage-gated sodium channel gene. Three domains for a total of 1,107 bp were sequenced for every individual. Two populations from southern China were examined for pyrethroid resistance using the World Health Organization standard tube bioassay, and the association between kdr mutations and phenotypic resistance was tested. A total of 29 synonymous mutations were found across domain II, III and IV of the VGSC gene. Non-synonymous mutations in two codons of the VGSC gene were detected in 5 populations from 4 countries. A novel mutation at 1532 codon (I1532T) was found in Rome, Italy with a frequency of 19.7%. The second novel mutation at codon 1534 (F1534S) was detected in southern China and Florida, USA with a frequency ranging from 9.5-22.6%. The WHO insecticide susceptibility bioassay found 90.1% and 96.1% mortality in the two populations from southern China, suggesting resistance and probable resistance. Positive association between kdr mutations with deltamethrin resistance was established in these two populations. Two novel kdr mutations, I1532T

  16. The Cytochrome P450 gene CYP6P12 confers pyrethroid resistance in kdr-free Malaysian populations of the dengue vector Aedes albopictus.

    Science.gov (United States)

    Ishak, Intan H; Riveron, Jacob M; Ibrahim, Sulaiman S; Stott, Rob; Longbottom, Joshua; Irving, Helen; Wondji, Charles S

    2016-04-20

    Control of Aedes albopictus, major dengue and chikungunya vector, is threatened by growing cases of insecticide resistance. The mechanisms driving this resistance remain poorly characterised. This study investigated the molecular basis of insecticide resistance in Malaysian populations of Ae. albopictus. Microarray-based transcription profiling revealed that metabolic resistance (cytochrome P450 up-regulation) and possibly a reduced penetration mechanism (consistent over-expression of cuticular protein genes) were associated with pyrethroid resistance. CYP6P12 over-expression was strongly associated with pyrethroid resistance whereas CYP6N3 was rather consistently over-expressed across carbamate and DDT resistant populations. Other detoxification genes also up-regulated in permethrin resistant mosquitoes included a glucuronosyltransferase (AAEL014279-RA) and the glutathione-S transferases GSTS1 and GSTT3. Functional analyses further supported that CYP6P12 contributes to pyrethroid resistance in Ae. albopictus as transgenic expression of CYP6P12 in Drosophila was sufficient to confer pyrethroid resistance in these flies. Furthermore, molecular docking simulations predicted CYP6P12 possessing enzymatic activity towards pyrethroids. Patterns of polymorphism suggested early sign of selection acting on CYP6P12 but not on CYP6N3. The major role played by P450 in the absence of kdr mutations suggests that addition of the synergist PBO to pyrethroids could improve the efficacy of this insecticide class and overcome resistance in field populations of Ae. albopictus.

  17. Multi-species sequence comparison reveals conservation of ghrelin gene-derived splice variants encoding a truncated ghrelin peptide.

    Science.gov (United States)

    Seim, Inge; Jeffery, Penny L; Thomas, Patrick B; Walpole, Carina M; Maugham, Michelle; Fung, Jenny N T; Yap, Pei-Yi; O'Keeffe, Angela J; Lai, John; Whiteside, Eliza J; Herington, Adrian C; Chopin, Lisa K

    2016-06-01

    The peptide hormone ghrelin is a potent orexigen produced predominantly in the stomach. It has a number of other biological actions, including roles in appetite stimulation, energy balance, the stimulation of growth hormone release and the regulation of cell proliferation. Recently, several ghrelin gene splice variants have been described. Here, we attempted to identify conserved alternative splicing of the ghrelin gene by cross-species sequence comparisons. We identified a novel human exon 2-deleted variant and provide preliminary evidence that this splice variant and in1-ghrelin encode a C-terminally truncated form of the ghrelin peptide, termed minighrelin. These variants are expressed in humans and mice, demonstrating conservation of alternative splicing spanning 90 million years. Minighrelin appears to have similar actions to full-length ghrelin, as treatment with exogenous minighrelin peptide stimulates appetite and feeding in mice. Forced expression of the exon 2-deleted preproghrelin variant mirrors the effect of the canonical preproghrelin, stimulating cell proliferation and migration in the PC3 prostate cancer cell line. This is the first study to characterise an exon 2-deleted preproghrelin variant and to demonstrate sequence conservation of ghrelin gene-derived splice variants that encode a truncated ghrelin peptide. This adds further impetus for studies into the alternative splicing of the ghrelin gene and the function of novel ghrelin peptides in vertebrates.

  18. Effects of Cetuximab Combined with Celecoxib on Apoptosis and KDR and AQP1 
Expression in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Honggang XIA

    2013-12-01

    Full Text Available Background and objective Neoadjuvant chemotherapy is a new development in the treatment of lung cancer. In recent years, cetuximab and celecoxib have been commonly used in this procedure. This study aims to explore the effect of cetuximab combined with celecoxib on apoptosis and KDR and AQP1 expression in lung cancer A549 cells. Method The cells were cultured in RPMI-1640 and then divided into four groups: control group, 1 nmol/L cetuximab group, 25 µmol/L celecoxib group, and 1 nmol/L cetuximab+25 µmol/L celecoxib group. The treatment time was 48 h. The mRNA and protein expression levels of KDR and AQP1 were detected by RT-PCR and Western blot, respectively. The apoptosis, proliferation, and invasive ability of A549 cells before and after transfection were examined using flow cytometry, MTT, and transwell methods. Results Cetuximab and celecoxib inhibited the growth of A549 cells in a dose-dependent manner. Their combination produced a greater growth inhibition than when either was used alone (P<0.01. Cetuximab and celecoxib both induced the apoptosis of A549 cells, and their combination produced a higher apoptosis rate (P<0.01. Cetuximab in combination with celecoxib also induced G1 phase arrest and downregulated the expression of KDR and AQP1 in A549 cells (P<0.05. As a result, the invasion ability of the A549 cells was significantly decreased. Conclusion Cetuximab in combination with celecoxib can synergistically inhibit the growth of A549 cells and downregulate the expression of KDR and AQP1 in A549 cells. The combination of cetuximab and celecoxib is a potential strategy for lung cancer therapy.

  19. Absence of kdr resistance alleles in the Union of the Comoros, East Africa [v1; ref status: indexed, http://f1000r.es/5fw

    Directory of Open Access Journals (Sweden)

    Yoosook Lee

    2015-06-01

    Full Text Available Knockdown resistance (kdr and CYP9K1 genotypes were detected by a MOLDI-TOF based SNP genotyping assay (Sequenom iPLEX in samples of Anopheles gambiae collected at 13 sites throughout the Union of the Comoros and Dar es Salaam, Tanzania during February and March 2011. All A. gambiae specimens collected in the Comoros were homozygous for the susceptible kdr alleles (+/+ while 96% of A. gambiae from Dar es Salaam were homozygous for the East African kdr resistant genotype (E/E. In contrast, all specimens from Dar es Salaam and the Comoros were homozygous for the cyp3 allele (c3/c3 at the CYP9K1 locus; the locus has been implicated in metabolic resistance against pyrethroid insecticides in West Africa. All specimens had typical A. gambiae genotypes for SNPs within the divergence Islands on all three chromosomes. Although further spatial and temporal studies are needed, the distribution of kdr genotypes between the Comoros and Tanzania further supports isolation of the Comoros populations from A. gambiae populations on mainland Africa.

  20. Truncating mutation in the NHS gene: phenotypic heterogeneity of Nance-Horan syndrome in an asian Indian family.

    Science.gov (United States)

    Ramprasad, Vedam Lakshmi; Thool, Alka; Murugan, Sakthivel; Nancarrow, Derek; Vyas, Prateep; Rao, Srinivas Kamalakar; Vidhya, Authiappan; Ravishankar, Krishnamoorthy; Kumaramanickavel, Govindasamy

    2005-01-01

    A four-generation family containing eight affected males who inherited X-linked developmental lens opacity and microcornea was studied. Some members in the family had mild to moderate nonocular clinical features suggestive of Nance-Horan syndrome. The purpose of the study was to map genetically the gene in the large 57-live-member Asian-Indian pedigree. PCR-based genotyping was performed on the X-chromosome, by using fluorescent microsatellite markers (10-cM intervals). Parametric linkage analysis was performed by using two disease models, assuming either recessive or dominant X-linked transmission by the MLINK/ILINK and FASTLINK (version 4.1P) programs (http:www.hgmp.mrc.ac.uk/; provided in the public domain by the Human Genome Mapping Project Resources Centre, Cambridge, UK). The NHS gene at the linked region was screened for mutation. By fine mapping, the disease gene was localized to Xp22.13. Multipoint analysis placed the peak LOD of 4.46 at DSX987. The NHS gene mapped to this region. Mutational screening in all the affected males and carrier females (heterozygous form) revealed a truncating mutation 115C-->T in exon 1, resulting in conversion of glutamine to stop codon (Q39X), but was not observed in unaffected individuals and control subjects. conclusions. A family with X-linked Nance-Horan syndrome had severe ocular, but mild to moderate nonocular, features. The clinical phenotype of the truncating mutation (Q39X) in the NHS gene suggests allelic heterogeneity at the NHS locus or the presence of modifier genes. X-linked families with cataract should be carefully examined for both ocular and nonocular features, to exclude Nance-Horan syndrome. RT-PCR analysis did not suggest nonsense-mediated mRNA decay as the possible mechanism for clinical heterogeneity.

  1. Kinase impact assessment in the landscape of fusion genes that retain kinase domains: a pan-cancer study

    Science.gov (United States)

    Kim, Pora; Jia, Peilin; Zhao, Zhongming

    2018-01-01

    Abstract Assessing the impact of kinase in gene fusion is essential for both identifying driver fusion genes (FGs) and developing molecular targeted therapies. Kinase domain retention is a crucial factor in kinase fusion genes (KFGs), but such a systematic investigation has not been done yet. To this end, we analyzed kinase domain retention (KDR) status in chimeric protein sequences of 914 KFGs covering 312 kinases across 13 major cancer types. Based on 171 kinase domain-retained KFGs including 101 kinases, we studied their recurrence, kinase groups, fusion partners, exon-based expression depth, short DNA motifs around the break points and networks. Our results, such as more KDR than 5′-kinase fusion genes, combinatorial effects between 3′-KDR kinases and their 5′-partners and a signal transduction-specific DNA sequence motif in the break point intronic sequences, supported positive selection on 3′-kinase fusion genes in cancer. We introduced a degree-of-frequency (DoF) score to measure the possible number of KFGs of a kinase. Interestingly, kinases with high DoF scores tended to undergo strong gene expression alteration at the break points. Furthermore, our KDR gene fusion network analysis revealed six of the seven kinases with the highest DoF scores (ALK, BRAF, MET, NTRK1, NTRK3 and RET) were all observed in thyroid carcinoma. Finally, we summarized common features of ‘effective’ (highly recurrent) kinases in gene fusions such as expression alteration at break point, redundant usage in multiple cancer types and 3′-location tendency. Collectively, our findings are useful for prioritizing driver kinases and FGs and provided insights into KFGs’ clinical implications. PMID:28013235

  2. First detection of multiple knockdown resistance (kdr)-like mutations in voltage-gated sodium channel using three new genotyping methods in Anopheles sinensis from Guangxi Province, China.

    Science.gov (United States)

    Tan, Wei L; Li, Chun X; Wang, Zhong M; Liu, Mei D; Dong, Yan D; Feng, Xiang Y; Wu, Zhi M; Guo, Xiao X; Xing, Dan; Zhang, Ying M; Wang, Zhong C; Zhao, Tong Y

    2012-09-01

    To investigate knockdown resistance (kdr)-like mutations associated with pyrethroid resistance in Anopheles sinensis (Wiedemann, 1828), from Guangxi province, southwest China, a segment of a sodium channel gene was sequenced and genotyped using three new genotyping assays. Direct sequencing revealed the presence of TTG-to-TCG and TG-to-TTT mutations at allele position L1014, which led to L1014S and L1014F substitutions in a few individual and two novel substitutions of N1013S and L1014W in two DNA templates. A low frequency of the kdr allele mostly in the heterozygous state of L1014S and L1014F was observed in this mosquito population. In this study, the genotyping of An. sinensis using three polymerase chain reaction-based methods generated consistent results, which agreed with the results of DNA sequencing. In total, 52 mosquitoes were genotyped using a direct sequencing assay. The number of mosquitoes and their genotypes were as follows: L/L = 24, L/S = 19, L/F = 8, and F/W = 1. The allelic frequency of L1014, 1014S, and 1014F were 72, 18, and 9%, respectively.

  3. Fusion events lead to truncation of FOS in epithelioid hemangioma of bone

    DEFF Research Database (Denmark)

    van IJzendoorn, David G P; de Jong, Danielle; Romagosa, Cleofe

    2015-01-01

    in exon 4 of the FOS gene and the fusion event led to the introduction of a stop codon. In all instances, the truncation of the FOS gene would result in the loss of the transactivation domain (TAD). Using FISH probes we found a break in the FOS gene in two additional cases, in none of these cases...... differential diagnosis of vascular tumors of bone. Our data suggest that the translocation causes truncation of the FOS protein, with loss of the TAD, which is thereby a novel mechanism involved in tumorigenesis....

  4. Truncating Mutations of MAGEL2, a Gene within the Prader-Willi Locus, Are Responsible for Severe Arthrogryposis

    Science.gov (United States)

    Mejlachowicz, Dan; Nolent, Flora; Maluenda, Jérome; Ranjatoelina-Randrianaivo, Hanitra; Giuliano, Fabienne; Gut, Ivo; Sternberg, Damien; Laquerrière, Annie; Melki, Judith

    2015-01-01

    Arthrogryposis multiplex congenita (AMC) is characterized by the presence of multiple joint contractures resulting from reduced or absent fetal movement. Here, we report two unrelated families affected by lethal AMC. By genetic mapping and whole-exome sequencing in a multiplex family, a heterozygous truncating MAGEL2 mutation leading to frameshift and a premature stop codon (c.1996delC, p.Gln666Serfs∗36) and inherited from the father was identified in the probands. In another family, a distinct heterozygous truncating mutation leading to frameshift (c.2118delT, p.Leu708Trpfs∗7) and occurring de novo on the paternal allele of MAGEL2 was identified in the affected individual. In both families, RNA analysis identified the mutated paternal MAGEL2 transcripts only in affected individuals. MAGEL2 is one of the paternally expressed genes within the Prader-Willi syndrome (PWS) locus. PWS is associated with, to varying extents, reduced fetal mobility, severe infantile hypotonia, childhood-onset obesity, hypogonadism, and intellectual disability. MAGEL2 mutations have been recently reported in affected individuals with features resembling PWS and called Schaaf-Yang syndrome. Here, we show that paternal MAGEL2 mutations are also responsible for lethal AMC, recapitulating the clinical spectrum of PWS and suggesting that MAGEL2 is a PWS-determining gene. PMID:26365340

  5. Replacement of the murine leukemia virus (MLV) envelope gene with a truncated HIV envelope gene in MLV generates a virus with impaired replication capacity

    International Nuclear Information System (INIS)

    Nack, Ursula; Schnierle, Barbara S.

    2003-01-01

    Murine leukemia virus (MLV) capsid particles can be efficiently pseudotyped with a variant of the HIV-1 envelope protein (Env) containing the surface glycoprotein gp120-SU and a carboxyl-terminally truncated transmembrane (TM) protein, with only seven cytoplasmic amino acids. MLV/HIV pseudotyped vector particles acquire the natural host tropism of HIV-1 and their entry is dependent on the presence of CD4 and an appropriate co-receptor on the surface of the target cell. We describe here the construction of chimeric MLV/HIV proviruses containing the truncated HIV envelope gene. The MLV/HIV provirus was generated by direct replacement of the MLV envelope gene with HIV Env coding sequences either with or without the additional inclusion of the woodchuck hepatitis virus posttranscriptional regulatory element (WPRE). Chimeric MLV/HIV particles could be generated from transfected 293T cells and were able to infect CD4/CXCR4-positive target cells. However, the second round of infection of target cells was severely impaired, despite the fact that the WPRE element enhanced the amount of viral mRNA detected. Viral particles released from infected cells showed reduced HIV Env incorporation, indicating that additional factors required for efficient replication of MLV/HIV pseudotyped viruses are missing

  6. Heterozygous truncation mutations of the SMC1A gene cause a severe early onset epilepsy with cluster seizures in females: Detailed phenotyping of 10 new cases.

    Science.gov (United States)

    Symonds, Joseph D; Joss, Shelagh; Metcalfe, Kay A; Somarathi, Suresh; Cruden, Jamie; Devlin, Anita M; Donaldson, Alan; DiDonato, Nataliya; Fitzpatrick, David; Kaiser, Frank J; Lampe, Anne K; Lees, Melissa M; McLellan, Ailsa; Montgomery, Tara; Mundada, Vivek; Nairn, Lesley; Sarkar, Ajoy; Schallner, Jens; Pozojevic, Jelena; Parenti, Ilaria; Tan, Jeen; Turnpenny, Peter; Whitehouse, William P; Zuberi, Sameer M

    2017-04-01

    The phenotype of seizure clustering with febrile illnesses in infancy/early childhood is well recognized. To date the only genetic epilepsy consistently associated with this phenotype is PCDH19, an X-linked disorder restricted to females, and males with mosaicism. The SMC1A gene, which encodes a structural component of the cohesin complex is also located on the X chromosome. Missense variants and small in-frame deletions of SMC1A cause approximately 5% of Cornelia de Lange Syndrome (CdLS). Recently, protein truncating mutations in SMC1A have been reported in five females, all of whom have been affected by a drug-resistant epilepsy, and severe developmental impairment. Our objective was to further delineate the phenotype of SMC1A truncation. Female cases with de novo truncation mutations in SMC1A were identified from the Deciphering Developmental Disorders (DDD) study (n = 8), from postmortem testing of an affected twin (n = 1), and from clinical testing with an epilepsy gene panel (n = 1). Detailed information on the phenotype in each case was obtained. Ten cases with heterozygous de novo mutations in the SMC1A gene are presented. All 10 mutations identified are predicted to result in premature truncation of the SMC1A protein. All cases are female, and none had a clinical diagnosis of CdLS. They presented with onset of epileptic seizures between <4 weeks and 28 months of age. In the majority of cases, a marked preponderance for seizures to occur in clusters was noted. Seizure clusters were associated with developmental regression. Moderate or severe developmental impairment was apparent in all cases. Truncation mutations in SMC1A cause a severe epilepsy phenotype with cluster seizures in females. These mutations are likely to be nonviable in males. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  7. Truncation of a mannanase from Trichoderma harzianum improves its enzymatic properties and expression efficiency in Trichoderma reesei.

    Science.gov (United States)

    Wang, Juan; Zeng, Desheng; Liu, Gang; Wang, Shaowen; Yu, Shaowen

    2014-01-01

    To obtain high expression efficiency of a mannanase gene, ThMan5A, cloned from Trichoderma harzianum MGQ2, both the full-length gene and a truncated gene (ThMan5AΔCBM) that contains only the catalytic domain, were expressed in Trichoderma reesei QM9414 using the strong constitutive promoter of the gene encoding pyruvate decarboxylase (pdc), and purified to homogeneity, respectively. We found that truncation of the gene improved its expression efficiency as well as the enzymatic properties of the encoded protein. The recombinant strain expressing ThMan5AΔCBM produced 2,460 ± 45.1 U/ml of mannanase activity in the culture supernatant; 2.3-fold higher than when expressing the full-length ThMan5A gene. In addition, the truncated mannanase had superior thermostability compared with the full-length enzyme and retained 100 % of its activity after incubation at 60 °C for 48 h. Our results clearly show that the truncated ThMan5A enzyme exhibited improved characteristics both in expression efficiency and in its thermal stability. These characteristics suggest that ThMan5AΔCBM has potential applications in the food, feed, paper, and pulp industries.

  8. Detection of knockdown resistance (kdr mutations in Anopheles gambiae: a comparison of two new high-throughput assays with existing methods

    Directory of Open Access Journals (Sweden)

    Ball Amanda

    2007-08-01

    Full Text Available Abstract Background Knockdown resistance (kdr is a well-characterized mechanism of resistance to pyrethroid insecticides in many insect species and is caused by point mutations of the pyrethroid target site the para-type sodium channel. The presence of kdr mutations in Anopheles gambiae, the most important malaria vector in Africa, has been monitored using a variety of molecular techniques. However, there are few reports comparing the performance of these different assays. In this study, two new high-throughput assays were developed and compared with four established techniques. Methods Fluorescence-based assays based on 1 TaqMan probes and 2 high resolution melt (HRM analysis were developed to detect kdr alleles in An. gambiae. Four previously reported techniques for kdr detection, Allele Specific Polymerase Chain Reaction (AS-PCR, Heated Oligonucleotide Ligation Assay (HOLA, Sequence Specific Oligonucleotide Probe – Enzyme-Linked ImmunoSorbent Assay (SSOP-ELISA and PCR-Dot Blot were also optimized. The sensitivity and specificity of all six assays was then compared in a blind genotyping trial of 96 single insect samples that included a variety of kdr genotypes and African Anopheline species. The relative merits of each assay was assessed based on the performance in the genotyping trial, the length/difficulty of each protocol, cost (both capital outlay and consumable cost, and safety (requirement for hazardous chemicals. Results The real-time TaqMan assay was both the most sensitive (with the lowest number of failed reactions and the most specific (with the lowest number of incorrect scores. Adapting the TaqMan assay to use a PCR machine and endpoint measurement with a fluorimeter showed a slight reduction in sensitivity and specificity. HRM initially gave promising results but was more sensitive to both DNA quality and quantity and consequently showed a higher rate of failure and incorrect scores. The sensitivity and specificity of AS

  9. Detection of knockdown resistance (kdr) mutations in Anopheles gambiae: a comparison of two new high-throughput assays with existing methods

    Science.gov (United States)

    Bass, Chris; Nikou, Dimitra; Donnelly, Martin J; Williamson, Martin S; Ranson, Hilary; Ball, Amanda; Vontas, John; Field, Linda M

    2007-01-01

    Background Knockdown resistance (kdr) is a well-characterized mechanism of resistance to pyrethroid insecticides in many insect species and is caused by point mutations of the pyrethroid target site the para-type sodium channel. The presence of kdr mutations in Anopheles gambiae, the most important malaria vector in Africa, has been monitored using a variety of molecular techniques. However, there are few reports comparing the performance of these different assays. In this study, two new high-throughput assays were developed and compared with four established techniques. Methods Fluorescence-based assays based on 1) TaqMan probes and 2) high resolution melt (HRM) analysis were developed to detect kdr alleles in An. gambiae. Four previously reported techniques for kdr detection, Allele Specific Polymerase Chain Reaction (AS-PCR), Heated Oligonucleotide Ligation Assay (HOLA), Sequence Specific Oligonucleotide Probe – Enzyme-Linked ImmunoSorbent Assay (SSOP-ELISA) and PCR-Dot Blot were also optimized. The sensitivity and specificity of all six assays was then compared in a blind genotyping trial of 96 single insect samples that included a variety of kdr genotypes and African Anopheline species. The relative merits of each assay was assessed based on the performance in the genotyping trial, the length/difficulty of each protocol, cost (both capital outlay and consumable cost), and safety (requirement for hazardous chemicals). Results The real-time TaqMan assay was both the most sensitive (with the lowest number of failed reactions) and the most specific (with the lowest number of incorrect scores). Adapting the TaqMan assay to use a PCR machine and endpoint measurement with a fluorimeter showed a slight reduction in sensitivity and specificity. HRM initially gave promising results but was more sensitive to both DNA quality and quantity and consequently showed a higher rate of failure and incorrect scores. The sensitivity and specificity of AS-PCR, SSOP-ELISA, PCR Dot

  10. A Post-Truncation Parameterization of Truncated Normal Technical Inefficiency

    OpenAIRE

    Christine Amsler; Peter Schmidt; Wen-Jen Tsay

    2013-01-01

    In this paper we consider a stochastic frontier model in which the distribution of technical inefficiency is truncated normal. In standard notation, technical inefficiency u is distributed as N^+ (μ,σ^2). This distribution is affected by some environmental variables z that may or may not affect the level of the frontier but that do affect the shortfall of output from the frontier. We will distinguish the pre-truncation mean (μ) and variance (σ^2) from the post-truncation mean μ_*=E(u) and var...

  11. Equivalence of truncated count mixture distributions and mixtures of truncated count distributions.

    Science.gov (United States)

    Böhning, Dankmar; Kuhnert, Ronny

    2006-12-01

    This article is about modeling count data with zero truncation. A parametric count density family is considered. The truncated mixture of densities from this family is different from the mixture of truncated densities from the same family. Whereas the former model is more natural to formulate and to interpret, the latter model is theoretically easier to treat. It is shown that for any mixing distribution leading to a truncated mixture, a (usually different) mixing distribution can be found so that the associated mixture of truncated densities equals the truncated mixture, and vice versa. This implies that the likelihood surfaces for both situations agree, and in this sense both models are equivalent. Zero-truncated count data models are used frequently in the capture-recapture setting to estimate population size, and it can be shown that the two Horvitz-Thompson estimators, associated with the two models, agree. In particular, it is possible to achieve strong results for mixtures of truncated Poisson densities, including reliable, global construction of the unique NPMLE (nonparametric maximum likelihood estimator) of the mixing distribution, implying a unique estimator for the population size. The benefit of these results lies in the fact that it is valid to work with the mixture of truncated count densities, which is less appealing for the practitioner but theoretically easier. Mixtures of truncated count densities form a convex linear model, for which a developed theory exists, including global maximum likelihood theory as well as algorithmic approaches. Once the problem has been solved in this class, it might readily be transformed back to the original problem by means of an explicitly given mapping. Applications of these ideas are given, particularly in the case of the truncated Poisson family.

  12. The expression of a truncated HMGI-C gene induces gigantism associated with lipomatosis.

    Science.gov (United States)

    Battista, S; Fidanza, V; Fedele, M; Klein-Szanto, A J; Outwater, E; Brunner, H; Santoro, M; Croce, C M; Fusco, A

    1999-10-01

    Rearrangements of the HMGI-C gene have frequently been detected in human benign tumors of mesenchymal origin, including lipomas. The HMGI-C protein has three AT-hook domains and an acidic COOH-terminal tail. The HMGI-C modifications consist in the loss of the C-tail and the fusion with ectopic sequences. Recent results show that the loss of the COOH-terminal region, rather than the acquisition of new sequences, is sufficient to confer to HMGI-C the ability to transform NIH3T3 cells. Therefore, transgenic mice carrying a HMGI-C construct (HMGI-C/T), containing only the three AT-hook domains, were generated. The HMGI-C/T mice showed a giant phenotype, together with a predominantly abdominal/pelvic lipomatosis, suggesting a pivotal role of the HMGI-C truncation in the generation of human lipomas.

  13. How Truncating Are 'Truncating Languages'? Evidence from Russian and German.

    Science.gov (United States)

    Rathcke, Tamara V

    Russian and German have pr eviously been described as 'truncating', or cutting off target frequencies of the phrase-final pitch trajectories when the time available for voicing is compromised. However, supporting evidence is rare and limited to only a few pitch categories. This paper reports a production study conducted to document pitch adjustments to linguistic materials, in which the amount of voicing available for the realization of a pitch pattern varies from relatively long to extremely short. Productions of nuclear H+L*, H* and L*+H pitch accents followed by a low boundary tone were investigated in the two languages. The results of the study show that speakers of both 'truncating languages' do not utilize truncation exclusively when accommodating to different segmental environments. On the contrary, they employ several strategies - among them is truncation but also compression and temporal re-alignment - to produce the target pitch categories under increasing time pressure. Given that speakers can systematically apply all three adjustment strategies to produce some pitch patterns (H* L% in German and Russian) while not using truncation in others (H+L* L% particularly in Russian), we question the effectiveness of the typological classification of these two languages as 'truncating'. Moreover, the phonetic detail of truncation varies considerably, both across and within the two languages, indicating that truncation cannot be easily modeled as a unified phenomenon. The results further suggest that the phrase-final pitch adjustments are sensitive to the phonological composition of the tonal string and the status of a particular tonal event (associated vs. boundary tone), and do not apply to falling vs. rising pitch contours across the board, as previously put forward for German. Implications for the intonational phonology and prosodic typology are addressed in the discussion. © 2017 S. Karger AG, Basel.

  14. Effects of feeding Bt MON810 maize to pigs for 110 days on peripheral immune response and digestive fate of the cry1Ab gene and truncated Bt toxin.

    Directory of Open Access Journals (Sweden)

    Maria C Walsh

    Full Text Available BACKGROUND: The objective of this study was to evaluate potential long-term (110 days and age-specific effects of feeding genetically modified Bt maize on peripheral immune response in pigs and to determine the digestive fate of the cry1Ab gene and truncated Bt toxin. METHODOLOGY/PRINCIPAL FINDINGS: Forty day old pigs (n = 40 were fed one of the following treatments: 1 isogenic maize-based diet for 110 days (isogenic; 2 Bt maize-based diet (MON810 for 110 days (Bt; 3 Isogenic maize-based diet for 30 days followed by Bt maize-based diet for 80 days (isogenic/Bt; and 4 Bt maize-based diet (MON810 for 30 days followed by isogenic maize-based diet for 80 days (Bt/isogenic. Blood samples were collected during the study for haematological analysis, measurement of cytokine and Cry1Ab-specific antibody production, immune cell phenotyping and cry1Ab gene and truncated Bt toxin detection. Pigs were sacrificed on day 110 and digesta and organ samples were taken for detection of the cry1Ab gene and the truncated Bt toxin. On day 100, lymphocyte counts were higher (P<0.05 in pigs fed Bt/isogenic than pigs fed Bt or isogenic. Erythrocyte counts on day 100 were lower in pigs fed Bt or isogenic/Bt than pigs fed Bt/isogenic (P<0.05. Neither the truncated Bt toxin nor the cry1Ab gene were detected in the organs or blood of pigs fed Bt maize. The cry1Ab gene was detected in stomach digesta and at low frequency in the ileum but not in the distal gastrointestinal tract (GIT, while the Bt toxin fragments were detected at all sites in the GIT. CONCLUSIONS/SIGNIFICANCE: Perturbations in peripheral immune response were thought not to be age-specific and were not indicative of Th 2 type allergenic or Th 1 type inflammatory responses. There was no evidence of cry1Ab gene or Bt toxin translocation to organs or blood following long-term feeding.

  15. Identification of a functionally distinct truncated BDNF mRNA splice variant and protein in Trachemys scripta elegans.

    Directory of Open Access Journals (Sweden)

    Ganesh Ambigapathy

    Full Text Available Brain-derived neurotrophic factor (BDNF has a diverse functional role and complex pattern of gene expression. Alternative splicing of mRNA transcripts leads to further diversity of mRNAs and protein isoforms. Here, we describe the regulation of BDNF mRNA transcripts in an in vitro model of eyeblink classical conditioning and a unique transcript that forms a functionally distinct truncated BDNF protein isoform. Nine different mRNA transcripts from the BDNF gene of the pond turtle Trachemys scripta elegans (tBDNF are selectively regulated during classical conditioning: exon I mRNA transcripts show no change, exon II transcripts are downregulated, while exon III transcripts are upregulated. One unique transcript that codes from exon II, tBDNF2a, contains a 40 base pair deletion in the protein coding exon that generates a truncated tBDNF protein. The truncated transcript and protein are expressed in the naïve untrained state and are fully repressed during conditioning when full-length mature tBDNF is expressed, thereby having an alternate pattern of expression in conditioning. Truncated BDNF is not restricted to turtles as a truncated mRNA splice variant has been described for the human BDNF gene. Further studies are required to determine the ubiquity of truncated BDNF alternative splice variants across species and the mechanisms of regulation and function of this newly recognized BDNF protein.

  16. Identification of a functionally distinct truncated BDNF mRNA splice variant and protein in Trachemys scripta elegans.

    Science.gov (United States)

    Ambigapathy, Ganesh; Zheng, Zhaoqing; Li, Wei; Keifer, Joyce

    2013-01-01

    Brain-derived neurotrophic factor (BDNF) has a diverse functional role and complex pattern of gene expression. Alternative splicing of mRNA transcripts leads to further diversity of mRNAs and protein isoforms. Here, we describe the regulation of BDNF mRNA transcripts in an in vitro model of eyeblink classical conditioning and a unique transcript that forms a functionally distinct truncated BDNF protein isoform. Nine different mRNA transcripts from the BDNF gene of the pond turtle Trachemys scripta elegans (tBDNF) are selectively regulated during classical conditioning: exon I mRNA transcripts show no change, exon II transcripts are downregulated, while exon III transcripts are upregulated. One unique transcript that codes from exon II, tBDNF2a, contains a 40 base pair deletion in the protein coding exon that generates a truncated tBDNF protein. The truncated transcript and protein are expressed in the naïve untrained state and are fully repressed during conditioning when full-length mature tBDNF is expressed, thereby having an alternate pattern of expression in conditioning. Truncated BDNF is not restricted to turtles as a truncated mRNA splice variant has been described for the human BDNF gene. Further studies are required to determine the ubiquity of truncated BDNF alternative splice variants across species and the mechanisms of regulation and function of this newly recognized BDNF protein.

  17. R Programs for Truncated Distributions

    Directory of Open Access Journals (Sweden)

    Saralees Nadarajah

    2006-08-01

    Full Text Available Truncated distributions arise naturally in many practical situations. In this note, we provide programs for computing six quantities of interest (probability density function, mean, variance, cumulative distribution function, quantile function and random numbers for any truncated distribution: whether it is left truncated, right truncated or doubly truncated. The programs are written in R: a freely downloadable statistical software.

  18. Molecular modelling studies of kdr mutations in voltage gated sodium channel revealed significant conformational variations contributing to insecticide resistance.

    Science.gov (United States)

    Yellapu, Nanda Kumar; Gopal, Jeyakodi; Kasinathan, Gunasekaran; Purushothaman, Jambulingam

    2018-06-01

    Voltage gated sodium channels (VGSC) of mosquito vectors are the primary targets of dichlorodiphenyltrichloroethane (DDT) and other synthetic pyrethroids used in public health programmes. The knockdown resistant (kdr) mutations in VGSC are associated with the insecticide resistance especially in Anophelines. The present study is aimed to emphasize and demarcate the impact of three kdr-mutations such as L1014S, L1014F and L1014H on insecticide resistance. The membrane model of sodium transport domain of VGSC (STD-VGSC) was constructed using de novo approach based on domain and trans-membrane predictions. The comparative molecular modelling studies of wild type and mutant models of STD-VGSC revealed that L1014F mutant was observed to be near native to the wild type model in all the respects, but, L1014S and L1014H mutations showed drastic variations in the energy levels, root mean square fluctuations (RMSF) that resulted in conformational variations. The predicted binding sites also showed variable cavity volumes and RMSF in L1014S and L1014H mutants. Further, DDT also found be bound in near native manner to wild type in L1014F mutant and with variable orientation and affinities in L1014S and L1014H mutants. The variations and fluctuations observed in mutant structures explained that each mutation has its specific impact on the conformation of VGSC and its binding with DDT. The study provides new insights into the structure-function-correlations of mutant STD-VGSC structures and demonstrates the role and effects of kdr mutations on insecticide resistance in mosquito vectors.

  19. Polymorphism of intron-1 in the voltage-gated sodium channel gene of Anopheles gambiae s.s. populations from Cameroon with emphasis on insecticide knockdown resistance mutations.

    Science.gov (United States)

    Etang, Josiane; Vicente, Jose L; Nwane, Philippe; Chouaibou, Mouhamadou; Morlais, Isabelle; Do Rosario, Virgilio E; Simard, Frederic; Awono-Ambene, Parfait; Toto, Jean Claude; Pinto, Joao

    2009-07-01

    Sequence variation at the intron-1 of the voltage-gated sodium channel gene in Anopheles gambiae M- and S-forms from Cameroon was assessed to explore the number of mutational events originating knockdown resistance (kdr) alleles. Mosquitoes were sampled between December 2005 and June 2006 from three geographical areas: (i) Magba in the western region; (ii) Loum, Tiko, Douala, Kribi, and Campo along the Atlantic coast; and (iii) Bertoua, in the eastern continental plateau. Both 1014S and 1014F kdr alleles were found in the S-form with overall frequencies of 14% and 42% respectively. Only the 1014F allele was found in the M-form at lower frequency (11%). Analysis of a 455 bp region of intron-1 upstream the kdr locus revealed four independent mutation events originating kdr alleles, here named MS1 -1014F, S1-1014S and S2-1014S kdr-intron-1 haplotypes in S-form and MS3-1014F kdr-intron-1 haplotype in the M-form. Furthermore, there was evidence for mutual introgression of kdr 1014F allele between the two molecular forms, MS1 and MS3 being widely shared by them. Although no M/S hybrid was observed in analysed samples, this wide distribution of haplotypes MS1 and MS3 suggests inter-form hybridizing at significant level and emphasizes the rapid diffusion of the kdr alleles in Africa. The mosaic of genetic events found in Cameroon is representative of the situation in the West-Central African region and highlights the importance of evaluating the spatial and temporal evolution of kdr alleles for a better management of insecticide resistance.

  20. The truncated splice variant of peroxisome proliferator-activated receptor alpha, PPARα-tr, autonomously regulates proliferative and pro-inflammatory genes

    International Nuclear Information System (INIS)

    Thomas, Maria; Bayha, Christine; Klein, Kathrin; Müller, Simon; Weiss, Thomas S.; Schwab, Matthias; Zanger, Ulrich M.

    2015-01-01

    The peroxisome proliferator-activated receptor alpha (PPARα) controls lipid/energy homeostasis and inflammatory responses. The truncated splice variant PPARα-tr was suggested to exert a dominant negative function despite being unable to bind consensus PPARα DNA response elements. The distribution and variability factor of each PPARα variant were assessed in the well-characterized cohort of human liver samples (N = 150) on the mRNA and protein levels. Specific siRNA-mediated downregulation of each transcript as well as specific overexpression with subsequent qRT-PCR analysis of downstream genes was used for investigation of specific functional roles of PPARα-wt and PPARα-tr forms in primary human hepatocytes. Bioinformatic analyses of genome-wide liver expression profiling data suggested a possible role of PPARα-tr in downregulating proliferative and pro-inflammatory genes. Specific gene silencing of both forms in primary human hepatocytes showed that induction of metabolic PPARα-target genes by agonist WY14,643 was prevented by PPARα-wt knock-down but neither prevented nor augmented by PPARα-tr knock-down. WY14,643 treatment did not induce proliferative genes including MYC, CDK1, and PCNA, and knock-down of PPARα-wt had no effect, while PPARα-tr knock-down caused up to 3-fold induction of these genes. Similarly, induction of pro-inflammatory genes IL1B, PTGS2, and CCL2 by IL-6 was augmented by knock-down of PPARα-tr but not of PPARα-wt. In contrast to human proliferative genes, orthologous mouse genes were readily inducible by WY14,643 in PPARα-tr non-expressing AML12 mouse hepatocytes. Induction was augmented by overexpression of PPARα-wt and attenuated by overexpression of PPARα-tr. Pro-inflammatory genes including IL-1β, CCL2 and TNFα were induced by WY14,643 in mouse and human cells and both PPARα forms attenuated induction. As potential mechanism of PPARα-tr inhibitory action we suggest crosstalk with WNT/β-catenin pathway. Finally

  1. Mel-18, a mammalian Polycomb gene, regulates angiogenic gene expression of endothelial cells.

    Science.gov (United States)

    Jung, Ji-Hye; Choi, Hyun-Jung; Maeng, Yong-Sun; Choi, Jung-Yeon; Kim, Minhyung; Kwon, Ja-Young; Park, Yong-Won; Kim, Young-Myeong; Hwang, Daehee; Kwon, Young-Guen

    2010-10-01

    Mel-18 is a mammalian homolog of Polycomb group (PcG) genes. Microarray analysis revealed that Mel-18 expression was induced during endothelial progenitor cell (EPC) differentiation and correlates with the expression of EC-specific protein markers. Overexpression of Mel-18 promoted EPC differentiation and angiogenic activity of ECs. Accordingly, silencing Mel-18 inhibited EC migration and tube formation in vitro. Gene expression profiling showed that Mel-18 regulates angiogenic genes including kinase insert domain receptor (KDR), claudin 5, and angiopoietin-like 2. Our findings demonstrate, for the first time, that Mel-18 plays a significant role in the angiogenic function of ECs by regulating endothelial gene expression. Copyright © 2010 Elsevier Inc. All rights reserved.

  2. Scavenger receptor AI/II truncation, lung function and COPD

    DEFF Research Database (Denmark)

    Thomsen, M; Nordestgaard, B G; Tybjaerg-Hansen, A

    2011-01-01

    The scavenger receptor A-I/II (SRA-I/II) on alveolar macrophages is involved in recognition and clearance of modified lipids and inhaled particulates. A rare variant of the SRA-I/II gene, Arg293X, truncates the distal collagen-like domain, which is essential for ligand recognition. We tested whet...

  3. Detection of 1014F kdr mutation in four major Anopheline malaria vectors in Indonesia

    Directory of Open Access Journals (Sweden)

    Sukowati Supratman

    2010-11-01

    Full Text Available Abstract Background Malaria is a serious public health problem in Indonesia, particularly in areas outside Java and Bali. The spread of resistance to the currently available anti-malarial drugs or insecticides used for mosquito control would cause an increase in malaria transmission. To better understand patterns of transmission and resistance in Indonesia, an integrated mosquito survey was conducted in three areas with different malaria endemicities, Purworejo in Central Java, South Lampung District in Sumatera and South Halmahera District in North Mollucca. Methods Mosquitoes were collected from the three areas through indoor and outdoor human landing catches (HLC and indoor restinging catches. Specimens were identified morphologically by species and kept individually in 1.5 ml Eppendorf microtube. A fragment of the VGSC gene from 95 mosquito samples was sequenced and kdr allelic variation determined. Results The molecular analysis of these anopheline mosquitoes revealed the existence of the 1014F allele in 4 major malaria vectors from South Lampung. These species include, Anopheles sundaicus, Anopheles aconitus, Anopheles subpictus and Anopheles vagus. The 1014F allele was not found in the other areas. Conclusion The finding documents the presence of this mutant allele in Indonesia, and implies that selection pressure on the Anopheles population in this area has occurred. Further studies to determine the impact of the resistance allele on the efficacy of pyrethroids in control programmes are needed.

  4. Detection of 1014F kdr mutation in four major Anopheline malaria vectors in Indonesia.

    Science.gov (United States)

    Syafruddin, Din; Hidayati, Anggi P N; Asih, Puji B S; Hawley, William A; Sukowati, Supratman; Lobo, Neil F

    2010-11-08

    Malaria is a serious public health problem in Indonesia, particularly in areas outside Java and Bali. The spread of resistance to the currently available anti-malarial drugs or insecticides used for mosquito control would cause an increase in malaria transmission. To better understand patterns of transmission and resistance in Indonesia, an integrated mosquito survey was conducted in three areas with different malaria endemicities, Purworejo in Central Java, South Lampung District in Sumatera and South Halmahera District in North Mollucca. Mosquitoes were collected from the three areas through indoor and outdoor human landing catches (HLC) and indoor restinging catches. Specimens were identified morphologically by species and kept individually in 1.5 ml Eppendorf microtube. A fragment of the VGSC gene from 95 mosquito samples was sequenced and kdr allelic variation determined. The molecular analysis of these anopheline mosquitoes revealed the existence of the 1014F allele in 4 major malaria vectors from South Lampung. These species include, Anopheles sundaicus, Anopheles aconitus, Anopheles subpictus and Anopheles vagus. The 1014F allele was not found in the other areas. The finding documents the presence of this mutant allele in Indonesia, and implies that selection pressure on the Anopheles population in this area has occurred. Further studies to determine the impact of the resistance allele on the efficacy of pyrethroids in control programmes are needed.

  5. Zero-truncated negative binomial - Erlang distribution

    Science.gov (United States)

    Bodhisuwan, Winai; Pudprommarat, Chookait; Bodhisuwan, Rujira; Saothayanun, Luckhana

    2017-11-01

    The zero-truncated negative binomial-Erlang distribution is introduced. It is developed from negative binomial-Erlang distribution. In this work, the probability mass function is derived and some properties are included. The parameters of the zero-truncated negative binomial-Erlang distribution are estimated by using the maximum likelihood estimation. Finally, the proposed distribution is applied to real data, the number of methamphetamine in the Bangkok, Thailand. Based on the results, it shows that the zero-truncated negative binomial-Erlang distribution provided a better fit than the zero-truncated Poisson, zero-truncated negative binomial, zero-truncated generalized negative-binomial and zero-truncated Poisson-Lindley distributions for this data.

  6. Angular truncation errors in integrating nephelometry

    International Nuclear Information System (INIS)

    Moosmueller, Hans; Arnott, W. Patrick

    2003-01-01

    Ideal integrating nephelometers integrate light scattered by particles over all directions. However, real nephelometers truncate light scattered in near-forward and near-backward directions below a certain truncation angle (typically 7 deg. ). This results in truncation errors, with the forward truncation error becoming important for large particles. Truncation errors are commonly calculated using Mie theory, which offers little physical insight and no generalization to nonspherical particles. We show that large particle forward truncation errors can be calculated and understood using geometric optics and diffraction theory. For small truncation angles (i.e., <10 deg. ) as typical for modern nephelometers, diffraction theory by itself is sufficient. Forward truncation errors are, by nearly a factor of 2, larger for absorbing particles than for nonabsorbing particles because for large absorbing particles most of the scattered light is due to diffraction as transmission is suppressed. Nephelometers calibration procedures are also discussed as they influence the effective truncation error

  7. L1014F-kdr Mutation in Indian Anopheles subpictus (Diptera: Culicidae) Arising From Two Alternative Transversions in the Voltage-Gated Sodium Channel and a Single PIRA-PCR for Their Detection.

    Science.gov (United States)

    Singh, O P; Dykes, C L; Sharma, G; Das, M K

    2015-01-01

    Leucine-to-phenylalanine substitution at residue L1014 in the voltage-gated sodium channel, target site of action for dichlorodiphenyltrichloroethane (DDT) and pyrethroids, is the most common knockdown resistance (kdr) mutation reported in several insects conferring resistance against DDT and pyrethroids. Here, we report presence of two coexisting alternative transversions, A>T and A>C, on the third codon position of L1014 residue in malaria vector Anopheles subpictus Grassi (species A) from Jamshedpur (India), both leading to the same amino acid substitution of Leu-to-Phe with allelic frequencies of 19 and 67%, respectively. A single primer-introduced restriction analysis-polymerase chain reaction (PIRA-PCR) was devised for the identification of L1014F-kdr mutation in An. subpictus resulting from either type of point mutation. Genotyping of samples with PIRA-PCR revealed high frequency (82%) of L1014F-kdr mutation in the study area. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  8. LGI2 truncation causes a remitting focal epilepsy in dogs.

    Directory of Open Access Journals (Sweden)

    Eija H Seppälä

    2011-07-01

    Full Text Available One quadrillion synapses are laid in the first two years of postnatal construction of the human brain, which are then pruned until age 10 to 500 trillion synapses composing the final network. Genetic epilepsies are the most common neurological diseases with onset during pruning, affecting 0.5% of 2-10-year-old children, and these epilepsies are often characterized by spontaneous remission. We previously described a remitting epilepsy in the Lagotto romagnolo canine breed. Here, we identify the gene defect and affected neurochemical pathway. We reconstructed a large Lagotto pedigree of around 34 affected animals. Using genome-wide association in 11 discordant sib-pairs from this pedigree, we mapped the disease locus to a 1.7 Mb region of homozygosity in chromosome 3 where we identified a protein-truncating mutation in the Lgi2 gene, a homologue of the human epilepsy gene LGI1. We show that LGI2, like LGI1, is neuronally secreted and acts on metalloproteinase-lacking members of the ADAM family of neuronal receptors, which function in synapse remodeling, and that LGI2 truncation, like LGI1 truncations, prevents secretion and ADAM interaction. The resulting epilepsy onsets at around seven weeks (equivalent to human two years, and remits by four months (human eight years, versus onset after age eight in the majority of human patients with LGI1 mutations. Finally, we show that Lgi2 is expressed highly in the immediate post-natal period until halfway through pruning, unlike Lgi1, which is expressed in the latter part of pruning and beyond. LGI2 acts at least in part through the same ADAM receptors as LGI1, but earlier, ensuring electrical stability (absence of epilepsy during pruning years, preceding this same function performed by LGI1 in later years. LGI2 should be considered a candidate gene for common remitting childhood epilepsies, and LGI2-to-LGI1 transition for mechanisms of childhood epilepsy remission.

  9. The use of genetic programming in the analysis of quantitative gene expression profiles for identification of nodal status in bladder cancer

    International Nuclear Information System (INIS)

    Mitra, Anirban P; Almal, Arpit A; George, Ben; Fry, David W; Lenehan, Peter F; Pagliarulo, Vincenzo; Cote, Richard J; Datar, Ram H; Worzel, William P

    2006-01-01

    Previous studies on bladder cancer have shown nodal involvement to be an independent indicator of prognosis and survival. This study aimed at developing an objective method for detection of nodal metastasis from molecular profiles of primary urothelial carcinoma tissues. The study included primary bladder tumor tissues from 60 patients across different stages and 5 control tissues of normal urothelium. The entire cohort was divided into training and validation sets comprised of node positive and node negative subjects. Quantitative expression profiling was performed for a panel of 70 genes using standardized competitive RT-PCR and the expression values of the training set samples were run through an iterative machine learning process called genetic programming that employed an N-fold cross validation technique to generate classifier rules of limited complexity. These were then used in a voting algorithm to classify the validation set samples into those associated with or without nodal metastasis. The generated classifier rules using 70 genes demonstrated 81% accuracy on the validation set when compared to the pathological nodal status. The rules showed a strong predilection for ICAM1, MAP2K6 and KDR resulting in gene expression motifs that cumulatively suggested a pattern ICAM1>MAP2K6>KDR for node positive cases. Additionally, the motifs showed CDK8 to be lower relative to ICAM1, and ANXA5 to be relatively high by itself in node positive tumors. Rules generated using only ICAM1, MAP2K6 and KDR were comparably robust, with a single representative rule producing an accuracy of 90% when used by itself on the validation set, suggesting a crucial role for these genes in nodal metastasis. Our study demonstrates the use of standardized quantitative gene expression values from primary bladder tumor tissues as inputs in a genetic programming system to generate classifier rules for determining the nodal status. Our method also suggests the involvement of ICAM1, MAP2K6, KDR

  10. Truncated Groebner fans and lattice ideals

    OpenAIRE

    Lauritzen, Niels

    2005-01-01

    We outline a generalization of the Groebner fan of a homogeneous ideal with maximal cells parametrizing truncated Groebner bases. This "truncated" Groebner fan is usually much smaller than the full Groebner fan and offers the natural framework for conversion between truncated Groebner bases. The generic Groebner walk generalizes naturally to this setting by using the Buchberger algorithm with truncation on facets. We specialize to the setting of lattice ideals. Here facets along the generic w...

  11. Truncated SALL1 Impedes Primary Cilia Function in Townes-Brocks Syndrome

    DEFF Research Database (Denmark)

    Bozal-Basterra, Laura; Martín-Ruíz, Itziar; Pirone, Lucia

    2018-01-01

    by mutations in the gene encoding the transcriptional repressor SALL1 and is associated with the presence of a truncated protein that localizes to the cytoplasm. Here, we provide evidence that SALL1 mutations might cause TBS by means beyond its transcriptional capacity. By using proximity proteomics, we show...

  12. Statistical estimation for truncated exponential families

    CERN Document Server

    Akahira, Masafumi

    2017-01-01

    This book presents new findings on nonregular statistical estimation. Unlike other books on this topic, its major emphasis is on helping readers understand the meaning and implications of both regularity and irregularity through a certain family of distributions. In particular, it focuses on a truncated exponential family of distributions with a natural parameter and truncation parameter as a typical nonregular family. This focus includes the (truncated) Pareto distribution, which is widely used in various fields such as finance, physics, hydrology, geology, astronomy, and other disciplines. The family is essential in that it links both regular and nonregular distributions, as it becomes a regular exponential family if the truncation parameter is known. The emphasis is on presenting new results on the maximum likelihood estimation of a natural parameter or truncation parameter if one of them is a nuisance parameter. In order to obtain more information on the truncation, the Bayesian approach is also considere...

  13. NLO renormalization in the Hamiltonian truncation

    Science.gov (United States)

    Elias-Miró, Joan; Rychkov, Slava; Vitale, Lorenzo G.

    2017-09-01

    Hamiltonian truncation (also known as "truncated spectrum approach") is a numerical technique for solving strongly coupled quantum field theories, in which the full Hilbert space is truncated to a finite-dimensional low-energy subspace. The accuracy of the method is limited only by the available computational resources. The renormalization program improves the accuracy by carefully integrating out the high-energy states, instead of truncating them away. In this paper, we develop the most accurate ever variant of Hamiltonian Truncation, which implements renormalization at the cubic order in the interaction strength. The novel idea is to interpret the renormalization procedure as a result of integrating out exactly a certain class of high-energy "tail states." We demonstrate the power of the method with high-accuracy computations in the strongly coupled two-dimensional quartic scalar theory and benchmark it against other existing approaches. Our work will also be useful for the future goal of extending Hamiltonian truncation to higher spacetime dimensions.

  14. Molecular evaluation of a novel missense mutation & an insertional truncating mutation in SUMF1 gene

    Directory of Open Access Journals (Sweden)

    Udhaya H Kotecha

    2014-01-01

    Full Text Available Background & objectives: Multiple suphphatase deficiency (MSD is an autosomal recessive disorder affecting the post translational activation of all enzymes of the sulphatase family. To date, approximately 30 different mutations have been identified in the causative gene, sulfatase modifying factor 1 (SUMF1. We describe here the mutation analysis of a case of MSD. Methods: The proband was a four year old boy with developmental delay followed by neuroregression. He had coarse facies, appendicular hypertonia, truncal ataxia and ichthyosis limited to both lower limbs. Radiographs showed dysostosis multiplex. Clinical suspicion of MSD was confirmed by enzyme analysis of four enzymes of the sulphatase group. Results: The patient was compound heterozygote for a c.451A>G (p.K151E substitution in exon 3 and a single base insertion mutation (c.690_691 InsT in exon 5 in the SUMF1 gene. The bioinformatic analysis of the missense mutation revealed no apparent effect on the overall structure. However, the mutated 151-amino acid residue was found to be adjacent to the substrate binding and the active site residues, thereby affecting the substrate binding and/or catalytic activity, resulting in almost complete loss of enzyme function. Conclusions: The two mutations identified in the present case were novel. This is perhaps the first report of an insertion mutation in SUMF1 causing premature truncation of the protein.

  15. Genetic analysis of Chinese families reveals a novel truncation allele of the retinitis pigmentosa GTPase regulator gene

    Directory of Open Access Journals (Sweden)

    Fang Hu

    2014-10-01

    Full Text Available AIM: To make comprehensive molecular diagnosis for retinitis pigmentosa (RP patients in a consanguineous Han Chinese family using next generation sequencing based Capture-NGS screen technology. METHODS: A five-generation Han Chinese family diagnosed as non-syndromic X-linked recessive RP (XLRP was recruited, including four affected males, four obligate female carriers and eleven unaffected family members. Capture-NGS was performed using a custom designed capture panel covers 163 known retinal disease genes including 47 RP genes, followed by the validation of detected mutation using Sanger sequencing in all recruited family members. RESULTS: Capture-NGS in one affected 47-year-old male reveals a novel mutation, c.2417_2418insG:p.E806fs, in exon ORF15 of RP GTPase regulator (RPGR gene results in a frameshift change that results in a premature stop codon and a truncated protein product. The mutation was further validated in three of four affected males and two of four female carriers but not in the other unaffected family members. CONCLUSION: We have identified a novel mutation, c.2417_2418insG:p.E806fs, in a Han Chinese family with XLRP. Our findings expand the mutation spectrum of RPGR and the phenotypic spectrum of XLRP in Han Chinese families, and confirms Capture-NGS could be an effective and economic approach for the comprehensive molecular diagnosis of RP.

  16. Gene inactivation in the plant pathogen Glomerella cingulata: three strategies for the disruption of the pectin lyase gene pnlA.

    Science.gov (United States)

    Bowen, J K; Templeton, M D; Sharrock, K R; Crowhurst, R N; Rikkerink, E H

    1995-01-20

    The feasibility of performing routine transformation-mediated mutagenesis in Glomerella cingulata was analysed by adopting three one-step gene disruption strategies targeted at the pectin lyase gene pnlA. The efficiencies of disruption following transformation with gene replacement- or gene truncation-disruption vectors were compared. To effect replacement-disruption, G. cingulata was transformed with a vector carrying DNA from the pnlA locus in which the majority of the coding sequence had been replaced by the gene for hygromycin B resistance. Two of the five transformants investigated contained an inactivated pnlA gene (pnlA-); both also contained ectopically integrated vector sequences. The efficacy of gene disruption by transformation with two gene truncation-disruption vectors was also assessed. Both vectors carried at 5' and 3' truncated copy of the pnlA coding sequence, adjacent to the gene for hygromycin B resistance. The promoter sequences controlling the selectable marker differed in the two vectors. In one vector the homologous G. cingulata gpdA promoter controlled hygromycin B phosphotransferase expression (homologous truncation vector), whereas in the second vector promoter elements were from the Aspergillus nidulans gpdA gene (heterologous truncation vector). Following transformation with the homologous truncation vector, nine transformants were analysed by Southern hybridisation; no transformants contained a disrupted pnlA gene. Of nineteen heterologous truncation vector transformants, three contained a disrupted pnlA gene; Southern analysis revealed single integrations of vector sequence at pnlA in two of these transformants. pnlA mRNA was not detected by Northern hybridisation in pnlA- transformants. pnlA- transformants failed to produce a PNLA protein with a pI identical to one normally detected in wild-type isolates by silver and activity staining of isoelectric focussing gels. Pathogenesis on Capsicum and apple was unaffected by disruption of

  17. Stability of Slopes Reinforced with Truncated Piles

    Directory of Open Access Journals (Sweden)

    Shu-Wei Sun

    2016-01-01

    Full Text Available Piles are extensively used as a means of slope stabilization. A novel engineering technique of truncated piles that are unlike traditional piles is introduced in this paper. A simplified numerical method is proposed to analyze the stability of slopes stabilized with truncated piles based on the shear strength reduction method. The influential factors, which include pile diameter, pile spacing, depth of truncation, and existence of a weak layer, are systematically investigated from a practical point of view. The results show that an optimum ratio exists between the depth of truncation and the pile length above a slip surface, below which truncating behavior has no influence on the piled slope stability. This optimum ratio is bigger for slopes stabilized with more flexible piles and piles with larger spacing. Besides, truncated piles are more suitable for slopes with a thin weak layer than homogenous slopes. In practical engineering, the piles could be truncated reasonably while ensuring the reinforcement effect. The truncated part of piles can be filled with the surrounding soil and compacted to reduce costs by using fewer materials.

  18. Adaptation of the delta-m and δ-fit truncation methods to vector radiative transfer: Effect of truncation on radiative transfer accuracy

    International Nuclear Information System (INIS)

    Sanghavi, Suniti; Stephens, Graeme

    2015-01-01

    In the presence of aerosol and/or clouds, the use of appropriate truncation methods becomes indispensable for accurate but cost-efficient radiative transfer computations. Truncation methods allow the reduction of the large number (usually several hundreds) of Fourier components associated with particulate scattering functions to a more manageable number, thereby making it possible to carry out radiative transfer computations with a modest number of streams. While several truncation methods have been discussed for scalar radiative transfer, few rigorous studies have been made of truncation methods for the vector case. Here, we formally derive the vector form of Wiscombe's delta-m truncation method. Two main sources of error associated with delta-m truncation are identified as the delta-separation error (DSE) and the phase-truncation error (PTE). The view angles most affected by truncation error occur in the vicinity of the direction of exact backscatter. This view geometry occurs commonly in satellite based remote sensing applications, and is hence of considerable importance. In order to deal with these errors, we adapt the δ-fit approach of Hu et al. (2000) [17] to vector radiative transfer. The resulting δBGE-fit is compared with the vectorized delta-m method. For truncation at l=25 of an original phase matrix consisting of over 300 Fourier components, the use of the δBGE-fit minimizes the error due to truncation at these view angles, while practically eliminating error at other angles. We also show how truncation errors have a distorting effect on hyperspectral absorption line shapes. The choice of the δBGE-fit method over delta-m truncation minimizes errors in absorption line depths, thus affording greater accuracy for sensitive retrievals such as those of XCO 2 from OCO-2 or GOSAT measurements. - Highlights: • Derives vector form for delta-m truncation method. • Adapts δ-fit truncation approach to vector RTE as δBGE-fit. • Compares truncation

  19. Computing correct truncated excited state wavefunctions

    Science.gov (United States)

    Bacalis, N. C.; Xiong, Z.; Zang, J.; Karaoulanis, D.

    2016-12-01

    We demonstrate that, if a wave function's truncated expansion is small, then the standard excited states computational method, of optimizing one "root" of a secular equation, may lead to an incorrect wave function - despite the correct energy according to the theorem of Hylleraas, Undheim and McDonald - whereas our proposed method [J. Comput. Meth. Sci. Eng. 8, 277 (2008)] (independent of orthogonality to lower lying approximants) leads to correct reliable small truncated wave functions. The demonstration is done in He excited states, using truncated series expansions in Hylleraas coordinates, as well as standard configuration-interaction truncated expansions.

  20. Mixtures of truncated basis functions

    DEFF Research Database (Denmark)

    Langseth, Helge; Nielsen, Thomas Dyhre; Rumí, Rafael

    2012-01-01

    In this paper we propose a framework, called mixtures of truncated basis functions (MoTBFs), for representing general hybrid Bayesian networks. The proposed framework generalizes both the mixture of truncated exponentials (MTEs) framework and the mixture of polynomials (MoPs) framework. Similar t...

  1. Applications of Fast Truncated Multiplication in Cryptography

    Directory of Open Access Journals (Sweden)

    Laszlo Hars

    2006-12-01

    Full Text Available Truncated multiplications compute truncated products, contiguous subsequences of the digits of integer products. For an n-digit multiplication algorithm of time complexity O(nα, with 1<α≤2, there is a truncated multiplication algorithm, which is constant times faster when computing a short enough truncated product. Applying these fast truncated multiplications, several cryptographic long integer arithmetic algorithms are improved, including integer reciprocals, divisions, Barrett and Montgomery multiplications, 2n-digit modular multiplication on hardware for n-digit half products. For example, Montgomery multiplication is performed in 2.6 Karatsuba multiplication time.

  2. Properties of truncated multiplicity distributions

    International Nuclear Information System (INIS)

    Lupia, S.

    1995-01-01

    Truncation effects on multiplicity distributions are discussed. Observables sensitive to the tail, like factorial moments, factorial cumulants and their ratio, are shown to be strongly affected by truncation. A possible way to overcome this problem by looking at the head of the distribution is suggested. (author)

  3. Properties of truncated multiplicity distributions

    Energy Technology Data Exchange (ETDEWEB)

    Lupia, S. [Turin Univ. (Italy). Dipt. di Fisica

    1995-12-31

    Truncation effects on multiplicity distributions are discussed. Observables sensitive to the tail, like factorial moments, factorial cumulants and their ratio, are shown to be strongly affected by truncation. A possible way to overcome this problem by looking at the head of the distribution is suggested. (author)

  4. Mutation avoidance and DNA repair proficiency in Ustilago maydis are differentially lost with progressive truncation of the REC1 gene product

    Energy Technology Data Exchange (ETDEWEB)

    Onel, K.; Thelen, M.P.; Ferguson, D.O.; Bennett, R.L.; Holloman, W.K. [Cornell Univ. Medical College, NY, NY (United States)

    1995-10-01

    The REC1 gene of Ustilago maydis has an uninterrupted open reading frame, predicted from the genomic sequence to encode a protein of 522 amino acid residues. Nevertheless, an intron is present, and functional activity of the gene in mitotic cells requires an RNA processing event to remove the intron. This results in a change in reading frame and production of a protein of 463 amino acid residues. The 3{prime}{r_arrow}5{prime} exonuclease activity of proteins derived form the REC1 genomic open reading frame, the intronless open reading frame, and several mutants was investigated. The mutants included a series of deletions constructed by removing restriction fragments at the 3{prime} end of the cloned REC1 gene and a set of mutant alleles previously isolated in screens for radiation sensitivity. The results indicated that elimination of the C-terminal third of the protein did not result in a serious reduction in 3{prime}{r_arrow}5{prime} exonuclease activity, but deletion into the midsection caused a severe loss of activity. The biological activity of the rec1-1 allele, which encodes a truncated polypeptide with full 3{prime}{r_arrow}5{prime} exonuclease activity, and the rec1-5 allele, which encodes a more severely truncated polypeptide with no exonuclease activity, was investigated. The two mutants were equally sensitive to the lethal effect of UV light, but the spontaneous mutation rate was elevated 10-fold over the wild-type rate in the rec1-1 mutant and 100-fold in the rec1-5 mutant. The elevated spontaneous mutation rate correlated with the ablation of exonuclease activity, but the radiation sensitivity did not. These results indicate that the C-terminal portion of the Rec1 protein is not essential for exonuclease activity but is crucial in the role of REC1 in DNA damage repair. 49 refs., 3 figs., 1 tab.

  5. Analysis of truncation limit in probabilistic safety assessment

    International Nuclear Information System (INIS)

    Cepin, Marko

    2005-01-01

    A truncation limit defines the boundaries of what is considered in the probabilistic safety assessment and what is neglected. The truncation limit that is the focus here is the truncation limit on the size of the minimal cut set contribution at which to cut off. A new method was developed, which defines truncation limit in probabilistic safety assessment. The method specifies truncation limits with more stringency than presenting existing documents dealing with truncation criteria in probabilistic safety assessment do. The results of this paper indicate that the truncation limits for more complex probabilistic safety assessments, which consist of larger number of basic events, should be more severe than presently recommended in existing documents if more accuracy is desired. The truncation limits defined by the new method reduce the relative errors of importance measures and produce more accurate results for probabilistic safety assessment applications. The reduced relative errors of importance measures can prevent situations, where the acceptability of change of equipment under investigation according to RG 1.174 would be shifted from region, where changes can be accepted, to region, where changes cannot be accepted, if the results would be calculated with smaller truncation limit

  6. Selective translational repression of truncated proteins from frameshift mutation-derived mRNAs in tumors.

    Directory of Open Access Journals (Sweden)

    Kwon Tae You

    2007-05-01

    Full Text Available Frameshift and nonsense mutations are common in tumors with microsatellite instability, and mRNAs from these mutated genes have premature termination codons (PTCs. Abnormal mRNAs containing PTCs are normally degraded by the nonsense-mediated mRNA decay (NMD system. However, PTCs located within 50-55 nucleotides of the last exon-exon junction are not recognized by NMD (NMD-irrelevant, and some PTC-containing mRNAs can escape from the NMD system (NMD-escape. We investigated protein expression from NMD-irrelevant and NMD-escape PTC-containing mRNAs by Western blotting and transfection assays. We demonstrated that transfection of NMD-irrelevant PTC-containing genomic DNA of MARCKS generates truncated protein. In contrast, NMD-escape PTC-containing versions of hMSH3 and TGFBR2 generate normal levels of mRNA, but do not generate detectable levels of protein. Transfection of NMD-escape mutant TGFBR2 genomic DNA failed to generate expression of truncated proteins, whereas transfection of wild-type TGFBR2 genomic DNA or mutant PTC-containing TGFBR2 cDNA generated expression of wild-type protein and truncated protein, respectively. Our findings suggest a novel mechanism of gene expression regulation for PTC-containing mRNAs in which the deleterious transcripts are regulated either by NMD or translational repression.

  7. Truncated Calogero-Sutherland models

    Science.gov (United States)

    Pittman, S. M.; Beau, M.; Olshanii, M.; del Campo, A.

    2017-05-01

    A one-dimensional quantum many-body system consisting of particles confined in a harmonic potential and subject to finite-range two-body and three-body inverse-square interactions is introduced. The range of the interactions is set by truncation beyond a number of neighbors and can be tuned to interpolate between the Calogero-Sutherland model and a system with nearest and next-nearest neighbors interactions discussed by Jain and Khare. The model also includes the Tonks-Girardeau gas describing impenetrable bosons as well as an extension with truncated interactions. While the ground state wave function takes a truncated Bijl-Jastrow form, collective modes of the system are found in terms of multivariable symmetric polynomials. We numerically compute the density profile, one-body reduced density matrix, and momentum distribution of the ground state as a function of the range r and the interaction strength.

  8. Lamp with a truncated reflector cup

    Science.gov (United States)

    Li, Ming; Allen, Steven C.; Bazydola, Sarah; Ghiu, Camil-Daniel

    2013-10-15

    A lamp assembly, and method for making same. The lamp assembly includes first and second truncated reflector cups. The lamp assembly also includes at least one base plate disposed between the first and second truncated reflector cups, and a light engine disposed on a top surface of the at least one base plate. The light engine is configured to emit light to be reflected by one of the first and second truncated reflector cups.

  9. A novel homozygous truncating GNAT1 mutation implicated in retinal degeneration.

    Science.gov (United States)

    Carrigan, Matthew; Duignan, Emma; Humphries, Pete; Palfi, Arpad; Kenna, Paul F; Farrar, G Jane

    2016-04-01

    The GNAT1 gene encodes the α subunit of the rod transducin protein, a key element in the rod phototransduction cascade. Variants in GNAT1 have been implicated in stationary night-blindness in the past, but unlike other proteins in the same pathway, it has not previously been implicated in retinitis pigmentosa. A panel of 182 retinopathy-associated genes was sequenced to locate disease-causing mutations in patients with inherited retinopathies. Sequencing revealed a novel homozygous truncating mutation in the GNAT1 gene in a patient with significant pigmentary disturbance and constriction of visual fields, a presentation consistent with retinitis pigmentosa. This is the first report of a patient homozygous for a complete loss-of-function GNAT1 mutation. The clinical data from this patient provide definitive evidence of retinitis pigmentosa with late onset in addition to the lifelong night-blindness that would be expected from a lack of transducin function. These data suggest that some truncating GNAT1 variants can indeed cause a recessive, mild, late-onset retinal degeneration in human beings rather than just stationary night-blindness as reported previously, with notable similarities to the phenotype of the Gnat1 knockout mouse. 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/

  10. Formal truncations of connected kernel equations

    International Nuclear Information System (INIS)

    Dixon, R.M.

    1977-01-01

    The Connected Kernel Equations (CKE) of Alt, Grassberger and Sandhas (AGS); Kouri, Levin and Tobocman (KLT); and Bencze, Redish and Sloan (BRS) are compared against reaction theory criteria after formal channel space and/or operator truncations have been introduced. The Channel Coupling Class concept is used to study the structure of these CKE's. The related wave function formalism of Sandhas, of L'Huillier, Redish and Tandy and of Kouri, Krueger and Levin are also presented. New N-body connected kernel equations which are generalizations of the Lovelace three-body equations are derived. A method for systematically constructing fewer body models from the N-body BRS and generalized Lovelace (GL) equations is developed. The formally truncated AGS, BRS, KLT and GL equations are analyzed by employing the criteria of reciprocity and two-cluster unitarity. Reciprocity considerations suggest that formal truncations of BRS, KLT and GL equations can lead to reciprocity-violating results. This study suggests that atomic problems should employ three-cluster connected truncations and that the two-cluster connected truncations should be a useful starting point for nuclear systems

  11. Perspective on rainbow-ladder truncation

    International Nuclear Information System (INIS)

    Eichmann, G.; Alkofer, R.; Krassnigg, A.; Cloeet, I. C.; Roberts, C. D.

    2008-01-01

    Prima facie the systematic implementation of corrections to the rainbow-ladder truncation of QCD's Dyson-Schwinger equations will uniformly reduce in magnitude those calculated mass-dimensioned results for pseudoscalar and vector meson properties that are not tightly constrained by symmetries. The aim and interpretation of studies employing rainbow-ladder truncation are reconsidered in this light

  12. Clustered survival data with left-truncation

    DEFF Research Database (Denmark)

    Eriksson, Frank; Martinussen, Torben; Scheike, Thomas H.

    2015-01-01

    Left-truncation occurs frequently in survival studies, and it is well known how to deal with this for univariate survival times. However, there are few results on how to estimate dependence parameters and regression effects in semiparametric models for clustered survival data with delayed entry....... Surprisingly, existing methods only deal with special cases. In this paper, we clarify different kinds of left-truncation and suggest estimators for semiparametric survival models under specific truncation schemes. The large-sample properties of the estimators are established. Small-sample properties...

  13. Expression and characterization of an N-truncated form of the NifA protein of Azospirillum brasilense

    Directory of Open Access Journals (Sweden)

    C.Y. Nishikawa

    2012-02-01

    Full Text Available Azospirillum brasilense is a nitrogen-fixing bacterium associated with important agricultural crops such as rice, wheat and maize. The expression of genes responsible for nitrogen fixation (nif genes in this bacterium is dependent on the transcriptional activator NifA. This protein contains three structural domains: the N-terminal domain is responsible for the negative control by fixed nitrogen; the central domain interacts with the RNA polymerase σ54 co-factor and the C-terminal domain is involved in DNA binding. The central and C-terminal domains are linked by the interdomain linker (IDL. A conserved four-cysteine motif encompassing the end of the central domain and the IDL is probably involved in the oxygen-sensitivity of NifA. In the present study, we have expressed, purified and characterized an N-truncated form of A. brasilense NifA. The protein expression was carried out in Escherichia coli and the N-truncated NifA protein was purified by chromatography using an affinity metal-chelating resin followed by a heparin-bound resin. Protein homogeneity was determined by densitometric analysis. The N-truncated protein activated in vivo nifH::lacZ transcription regardless of fixed nitrogen concentration (absence or presence of 20 mM NH4Cl but only under low oxygen levels. On the other hand, the aerobically purified N-truncated NifA protein bound to the nifB promoter, as demonstrated by an electrophoretic mobility shift assay, implying that DNA-binding activity is not strictly controlled by oxygen levels. Our data show that, while the N-truncated NifA is inactive in vivo under aerobic conditions, it still retains DNA-binding activity, suggesting that the oxidized form of NifA bound to DNA is not competent to activate transcription.

  14. Expression and characterization of an N-truncated form of the NifA protein of Azospirillum brasilense

    Energy Technology Data Exchange (ETDEWEB)

    Nishikawa, C.Y.; Araújo, L.M.; Kadowaki, M.A.S.; Monteiro, R.A.; Steffens, M.B.R.; Pedrosa, F.O.; Souza, E.M.; Chubatsu, L.S. [Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, PR (Brazil)

    2012-01-27

    Azospirillum brasilense is a nitrogen-fixing bacterium associated with important agricultural crops such as rice, wheat and maize. The expression of genes responsible for nitrogen fixation (nif genes) in this bacterium is dependent on the transcriptional activator NifA. This protein contains three structural domains: the N-terminal domain is responsible for the negative control by fixed nitrogen; the central domain interacts with the RNA polymerase σ{sup 54} factor and the C-terminal domain is involved in DNA binding. The central and C-terminal domains are linked by the interdomain linker (IDL). A conserved four-cysteine motif encompassing the end of the central domain and the IDL is probably involved in the oxygen-sensitivity of NifA. In the present study, we have expressed, purified and characterized an N-truncated form of A. brasilense NifA. The protein expression was carried out in Escherichia coli and the N-truncated NifA protein was purified by chromatography using an affinity metal-chelating resin followed by a heparin-bound resin. Protein homogeneity was determined by densitometric analysis. The N-truncated protein activated in vivo nifH::lacZ transcription regardless of fixed nitrogen concentration (absence or presence of 20 mM NH{sub 4}Cl) but only under low oxygen levels. On the other hand, the aerobically purified N-truncated NifA protein bound to the nifB promoter, as demonstrated by an electrophoretic mobility shift assay, implying that DNA-binding activity is not strictly controlled by oxygen levels. Our data show that, while the N-truncated NifA is inactive in vivo under aerobic conditions, it still retains DNA-binding activity, suggesting that the oxidized form of NifA bound to DNA is not competent to activate transcription.

  15. Expression and characterization of an N-truncated form of the NifA protein of Azospirillum brasilense.

    Science.gov (United States)

    Nishikawa, C Y; Araújo, L M; Kadowaki, M A S; Monteiro, R A; Steffens, M B R; Pedrosa, F O; Souza, E M; Chubatsu, L S

    2012-02-01

    Azospirillum brasilense is a nitrogen-fixing bacterium associated with important agricultural crops such as rice, wheat and maize. The expression of genes responsible for nitrogen fixation (nif genes) in this bacterium is dependent on the transcriptional activator NifA. This protein contains three structural domains: the N-terminal domain is responsible for the negative control by fixed nitrogen; the central domain interacts with the RNA polymerase σ(54) co-factor and the C-terminal domain is involved in DNA binding. The central and C-terminal domains are linked by the interdomain linker (IDL). A conserved four-cysteine motif encompassing the end of the central domain and the IDL is probably involved in the oxygen-sensitivity of NifA. In the present study, we have expressed, purified and characterized an N-truncated form of A. brasilense NifA. The protein expression was carried out in Escherichia coli and the N-truncated NifA protein was purified by chromatography using an affinity metal-chelating resin followed by a heparin-bound resin. Protein homogeneity was determined by densitometric analysis. The N-truncated protein activated in vivo nifH::lacZ transcription regardless of fixed nitrogen concentration (absence or presence of 20 mM NH(4)Cl) but only under low oxygen levels. On the other hand, the aerobically purified N-truncated NifA protein bound to the nifB promoter, as demonstrated by an electrophoretic mobility shift assay, implying that DNA-binding activity is not strictly controlled by oxygen levels. Our data show that, while the N-truncated NifA is inactive in vivo under aerobic conditions, it still retains DNA-binding activity, suggesting that the oxidized form of NifA bound to DNA is not competent to activate transcription.

  16. Expression and characterization of an N-truncated form of the NifA protein of Azospirillum brasilense

    International Nuclear Information System (INIS)

    Nishikawa, C.Y.; Araújo, L.M.; Kadowaki, M.A.S.; Monteiro, R.A.; Steffens, M.B.R.; Pedrosa, F.O.; Souza, E.M.; Chubatsu, L.S.

    2012-01-01

    Azospirillum brasilense is a nitrogen-fixing bacterium associated with important agricultural crops such as rice, wheat and maize. The expression of genes responsible for nitrogen fixation (nif genes) in this bacterium is dependent on the transcriptional activator NifA. This protein contains three structural domains: the N-terminal domain is responsible for the negative control by fixed nitrogen; the central domain interacts with the RNA polymerase σ 54 factor and the C-terminal domain is involved in DNA binding. The central and C-terminal domains are linked by the interdomain linker (IDL). A conserved four-cysteine motif encompassing the end of the central domain and the IDL is probably involved in the oxygen-sensitivity of NifA. In the present study, we have expressed, purified and characterized an N-truncated form of A. brasilense NifA. The protein expression was carried out in Escherichia coli and the N-truncated NifA protein was purified by chromatography using an affinity metal-chelating resin followed by a heparin-bound resin. Protein homogeneity was determined by densitometric analysis. The N-truncated protein activated in vivo nifH::lacZ transcription regardless of fixed nitrogen concentration (absence or presence of 20 mM NH 4 Cl) but only under low oxygen levels. On the other hand, the aerobically purified N-truncated NifA protein bound to the nifB promoter, as demonstrated by an electrophoretic mobility shift assay, implying that DNA-binding activity is not strictly controlled by oxygen levels. Our data show that, while the N-truncated NifA is inactive in vivo under aerobic conditions, it still retains DNA-binding activity, suggesting that the oxidized form of NifA bound to DNA is not competent to activate transcription

  17. Truncation correction for oblique filtering lines

    International Nuclear Information System (INIS)

    Hoppe, Stefan; Hornegger, Joachim; Lauritsch, Guenter; Dennerlein, Frank; Noo, Frederic

    2008-01-01

    State-of-the-art filtered backprojection (FBP) algorithms often define the filtering operation to be performed along oblique filtering lines in the detector. A limited scan field of view leads to the truncation of those filtering lines, which causes artifacts in the final reconstructed volume. In contrast to the case where filtering is performed solely along the detector rows, no methods are available for the case of oblique filtering lines. In this work, the authors present two novel truncation correction methods which effectively handle data truncation in this case. Method 1 (basic approach) handles data truncation in two successive preprocessing steps by applying a hybrid data extrapolation method, which is a combination of a water cylinder extrapolation and a Gaussian extrapolation. It is independent of any specific reconstruction algorithm. Method 2 (kink approach) uses similar concepts for data extrapolation as the basic approach but needs to be integrated into the reconstruction algorithm. Experiments are presented from simulated data of the FORBILD head phantom, acquired along a partial-circle-plus-arc trajectory. The theoretically exact M-line algorithm is used for reconstruction. Although the discussion is focused on theoretically exact algorithms, the proposed truncation correction methods can be applied to any FBP algorithm that exposes oblique filtering lines.

  18. Prokaryotic Expression of Truncate F Protein Gene of Newcastle Disease Virus%截短NDV F蛋白的原核表达

    Institute of Scientific and Technical Information of China (English)

    王杰; 王宇鹏; 刘振格; 杨鸣发; 林红丽; 田斌; 侯喜林

    2013-01-01

    根据NDV LaSota株F基因已知的抗原表位,对F蛋白进行分段表达。应用RT-PCR方法分段扩增F基因,并将其克隆到pET30a(+)原核表达载体上,得到重组质粒pET30-F780和pET30-F760,将质粒导入BL21(ED3)感受态中,经IPTG诱导表达。表达的重组蛋白通过SDS-PAGE和Westem-blotting方法进行鉴定。表达的两段蛋白大小约为31.1 kDa和27.9 kDa,与预期的蛋白分子量大小相符。Western blot分析表明重组蛋白可以和NDV抗体发生特异性反应。成功构建了原核表达质粒pET-F780和pET-F760,并获得了高效表达,通过Western blot分析表明重组蛋白具有良好的免疫反应性。%According to the epitopes of F gene of NDV LaSota strain,the F gene truncated two fragments were expressed in E.coli BL21 (ED3)strain. The two truncate F gene amplified by RT-PCR were inserted into pET30 (+),a prokaryotic expression vector. The recombinant plasmid pET30-F780 and pET30-F760 were transformed into BL21(ED3)competent cells. SDS-PAGE and Western-blotting screened the recombinant proteins induced by IPTG in E.coli. The size of the recombinant proteins were 31.1 kDa and 27.9 kDa,which were also consistent with those expected. Western-blotting showed that F780 and F760 were of immunogenicity.The recombinant plasmids were constructed,called pET-F780 and pET-F760,which were expressed the corresponding proteins with better immunoreactivity.

  19. Protein truncation test: analysis of two novel point mutations at the carboxy-terminus of the human dystrophin gene associated with mental retardation.

    Science.gov (United States)

    Tuffery, S; Lenk, U; Roberts, R G; Coubes, C; Demaille, J; Claustres, M

    1995-01-01

    Approximately one-third of the mutations responsible for Duchenne muscular dytrophy (DMD) do not involve gross rearrangements of the dystrophin gene. Methods for intensive mutation screening have recently been applied to this immense gene, which resulted in the identification of a number of point mutations in DMD patients, mostly translation-terminating mutations. A number of data raised the possibility that the C-terminal region of dystrophin might be involved in some cases of mental retardation associated with DMD. Using single-strand conformation analysis of products amplified by polymerase chain reaction (PCR-SSCA) to screen the terminal domains of the dystrophin gene (exons 60-79) of 20 unrelated patients with DMD or BMD, we detected two novel point mutations in two mentally retarded DMD patients: a 1-bp deletion in exon 70 (10334delC) and a 5' splice donor site alteration in intron 69 (10294 + 1G-->T). Both mutations should result in a premature translation termination of dystrophin. The possible effects on the reading frame were analyzed by the study of reverse transcripts amplified from peripheral blood lymphocytes mRNA and by the protein truncation test.

  20. Truncating SLC5A7 mutations underlie a spectrum of dominant hereditary motor neuropathies.

    Science.gov (United States)

    Salter, Claire G; Beijer, Danique; Hardy, Holly; Barwick, Katy E S; Bower, Matthew; Mademan, Ines; De Jonghe, Peter; Deconinck, Tine; Russell, Mark A; McEntagart, Meriel M; Chioza, Barry A; Blakely, Randy D; Chilton, John K; De Bleecker, Jan; Baets, Jonathan; Baple, Emma L; Walk, David; Crosby, Andrew H

    2018-04-01

    To identify the genetic cause of disease in 2 previously unreported families with forms of distal hereditary motor neuropathies (dHMNs). The first family comprises individuals affected by dHMN type V, which lacks the cardinal clinical feature of vocal cord paralysis characteristic of dHMN-VII observed in the second family. Next-generation sequencing was performed on the proband of each family. Variants were annotated and filtered, initially focusing on genes associated with neuropathy. Candidate variants were further investigated and confirmed by dideoxy sequence analysis and cosegregation studies. Thorough patient phenotyping was completed, comprising clinical history, examination, and neurologic investigation. dHMNs are a heterogeneous group of peripheral motor neuron disorders characterized by length-dependent neuropathy and progressive distal limb muscle weakness and wasting. We previously reported a dominant-negative frameshift mutation located in the concluding exon of the SLC5A7 gene encoding the choline transporter (CHT), leading to protein truncation, as the likely cause of dominantly-inherited dHMN-VII in an extended UK family. In this study, our genetic studies identified distinct heterozygous frameshift mutations located in the last coding exon of SLC5A7 , predicted to result in the truncation of the CHT C-terminus, as the likely cause of the condition in each family. This study corroborates C-terminal CHT truncation as a cause of autosomal dominant dHMN, confirming upper limb predominating over lower limb involvement, and broadening the clinical spectrum arising from CHT malfunction.

  1. Analysis of the upper-truncated Weibull distribution for wind speed

    International Nuclear Information System (INIS)

    Kantar, Yeliz Mert; Usta, Ilhan

    2015-01-01

    Highlights: • Upper-truncated Weibull distribution is proposed to model wind speed. • Upper-truncated Weibull distribution nests Weibull distribution as special case. • Maximum likelihood is the best method for upper-truncated Weibull distribution. • Fitting accuracy of upper-truncated Weibull is analyzed on wind speed data. - Abstract: Accurately modeling wind speed is critical in estimating the wind energy potential of a certain region. In order to model wind speed data smoothly, several statistical distributions have been studied. Truncated distributions are defined as a conditional distribution that results from restricting the domain of statistical distribution and they also cover base distribution. This paper proposes, for the first time, the use of upper-truncated Weibull distribution, in modeling wind speed data and also in estimating wind power density. In addition, a comparison is made between upper-truncated Weibull distribution and well known Weibull distribution using wind speed data measured in various regions of Turkey. The obtained results indicate that upper-truncated Weibull distribution shows better performance than Weibull distribution in estimating wind speed distribution and wind power. Therefore, upper-truncated Weibull distribution can be an alternative for use in the assessment of wind energy potential

  2. Knockdown resistance in pyrethroid-resistant horn fly (Diptera: Muscidae populations in Brazil Resistência Knockdown em populações de mosca-dos-chifres do Brasil resistentes aos piretróides

    Directory of Open Access Journals (Sweden)

    Gustavo A. Sabatini

    2009-09-01

    Full Text Available To investigate the kdr (knockdown resistance resistance-associated gene mutation and determine its frequency in pyrethroid-resistant horn fly (Haematobia irritans populations, a total of 1,804 horn flies of 37 different populations from all Brazilian regions (North, Northeast, Central-West, Southeast, and South were molecular screened through polymerase chain reaction (PCR. The kdr gene was not detected in 87.08% of the flies. However, the gene was amplified in 12.92% of the flies, of which 11.70% were resistant heterozygous and 1.22% were resistant homozygous. Deviation from Hardy-Weinberg equilibrium (HWE was found only in 1 ranch with an excess of heterozygous. When populations were grouped by region, three metapopulations showed significant deviations of HWE (Central-West population, South population and Southeast population. This indicates that populations are isolated one from another and kdr occurrence seems to be an independent effect probably reflecting the insecticide strategy used by each ranch. Although resistance to pyrethroids is disseminated throughout Brazil, only 48% of resistant populations had kdr flies, and the frequency of kdr individuals in each of these resistant populations was quite low. But this study shows that, with the apparent exception of the Northeast region, the kdr mechanism associated with pyrethroid resistance occurs all over Brazil.Com o objetivo de verificar a ocorrência e determinar a frequência da mutação kdr (knock down resistance em populações de Haematobia irritans (mosca-dos-chifres resistentes aos piretróides, foram analisados 1.804 indivíduos de 37 populações de todas as Regiões do Brasil. Com exceção da Região Nordeste, o kdr (knock down resistance gene foi encontrado em populações de todas as regiões. A mutação não foi detectada em 87,08% dos indivíduos. Entretanto, o gene foi amplificado de 12,92% das moscas, das quais 11,70% se mostraram heterozigotas resistentes e 1

  3. Expression of a truncated receptor protein tyrosine phosphatase kappa in the brain of an adult transgenic mouse

    DEFF Research Database (Denmark)

    Shen, P; Canoll, P D; Sap, J

    1999-01-01

    processes such as axonal growth and target recognition, as has been demonstrated for certain Drosophila RPTPs. The brain distribution of RPTP-kappa-expressing cells has not been determined, however. In a gene-trap mouse model with a beta-gal+neo (beta-geo) insertion in the endogenous RPTP-kappa gene......-6596]. Nevertheless, since the transgene's expression is driven by the endogenous RPTP-kappa promoter, distribution of the truncated RPTP-kappa/beta-geo fusion protein should reflect the regional and cellular expression of wild-type RPTP-kappa, and thus may identify sites where RPTP-kappa is important. Towards...... that goal, we have used this mouse model to map the distribution of the truncated RPTP-kappa/beta-geo fusion protein in the adult mouse brain using beta-galactosidase as a marker enzyme. Visualization of the beta-galactosidase activity revealed a non-random pattern of expression, and identified cells...

  4. First Detection of the Kdr Mutation T929I in Head Lice (Phthiraptera: Pediculidae) in Schoolchildren of the Metropolitan Area of Nuevo Leon and Yucatan, Mexico.

    Science.gov (United States)

    Ponce-Garcia, Gustavo; Villanueva-Segura, Karina; Trujillo-Rodriguez, Gerardo; Rodriguez-Sanchez, Iram P; Lopez-Monroy, Beatriz; Flores, Adriana E

    2017-07-01

    The head louse Pediculus humanus capitis (De Geer) is a hematophagous ectoparasite that inhabits the human scalp. Infestations by this insect are commonly known as pediculosis, which is more common in younger groups. These infestations are asymptomatic; however, skin irritation from scratching occasionally may cause secondary bacterial infections. In recent years, the prevalence of pediculosis has increased in children; this increase has been attributed to louse resistance to the insecticides used as a control measure for infestation. The aim of the present study was to determine the presence and frequency of the knockdown resistance mutation (kdr) T929I in 468 head lice collected from 32 elementary schools in the metropolitan area of Nuevo Leon (24) and Yucatan (8), Mexico. This is the first report of a knockdown resistance (kdr) mechanism in head lice from Mexico. The T929I mutation was present in all of the sampled schools, with variability observed in its allelic and genotypic frequencies. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. Functional Characterization of a Novel Truncating Mutation in Lamin A/C Gene in a Family with a Severe Cardiomyopathy with Conduction Defects

    Directory of Open Access Journals (Sweden)

    Andrea Gerbino

    2017-12-01

    Full Text Available Background/Aims: Truncating LMNA gene mutations occur in many inherited cardiomyopathy cases, but the molecular mechanisms involved in the disease they cause have not yet been systematically investigated. Here, we studied a novel frameshift LMNA variant (p.D243Gfs*4 identified in three members of an Italian family co-segregating with a severe form of cardiomyopathy with conduction defects. Methods: HEK293 cells and HL-1 cardiomyocytes were transiently transfected with either Lamin A or D243Gfs*4 tagged with GFP (or mCherry. D243Gfs*4 expression, cellular localization and its effects on diverse cellular mechanisms were evaluated with western blotting, laser-scanning confocal microscopy and video-imaging analysis in single cells. Results: When expressed in HEK293 cells, GFP- (or mCherry-tagged LMNA D243Gfs*4 colocalized with calnexin within the ER. ER mislocalization of LMNA D243Gfs*4 did not significantly induce ER stress response, abnormal Ca2+ handling and apoptosis when compared with HEK293 cells expressing another truncated mutant of LMNA (R321X which similarly accumulates within the ER. Of note, HEK293-LMNA D243Gfs*4 cells showed a significant reduction of connexin 43 (CX43 expression level, which was completely rescued by activation of the WNT/β-catenin signaling pathway. When expressed in HL-1 cardiomyocytes, D243Gfs*4 significantly impaired the spontaneous Ca2+ oscillations recorded in these cells as result of propagation of the depolarizing waves through the gap junctions between non-transfected cells surrounding a cell harboring the mutation. Furthermore, mCh-D243Gfs*4 HL-1 cardiomyocytes showed reduced CX43-dependent Lucifer Yellow (LY loading and propagation. Of note, activation of β-catenin rescued both LY loading and LMNA D243Gfs*4 -HL-1 cells spontaneous activity propagation. Conclusion: Overall, the present results clearly indicate the involvement of the aberrant CX43 expression/activity as a pathogenic mechanism for the

  6. New Schemes for Positive Real Truncation

    Directory of Open Access Journals (Sweden)

    Kari Unneland

    2007-07-01

    Full Text Available Model reduction, based on balanced truncation, of stable and of positive real systems are considered. An overview over some of the already existing techniques are given: Lyapunov balancing and stochastic balancing, which includes Riccati balancing. A novel scheme for positive real balanced truncation is then proposed, which is a combination of the already existing Lyapunov balancing and Riccati balancing. Using Riccati balancing, the solution of two Riccati equations are needed to obtain positive real reduced order systems. For the suggested method, only one Lyapunov equation and one Riccati equation are solved in order to obtain positive real reduced order systems, which is less computationally demanding. Further it is shown, that in order to get positive real reduced order systems, only one Riccati equation needs to be solved. Finally, this is used to obtain positive real frequency weighted balanced truncation.

  7. Trans-activation function of a 3' truncated X gene-cell fusion product from integrated hepatitis B virus DNA in chronic hepatitis tissues

    International Nuclear Information System (INIS)

    Takada, Shinako; Koike, Katsuro

    1990-01-01

    To investigate the expression and transactivation function of the X gene in integrated hepatitis B virus (HBV) DNA from chronic hepatitis tissues, a series of transfectants containing cloned integrated HBV DNAs was made and analyzed for X mRNA expression and trans-activation activity by using a chloramphenicol acetyltransferase assay. Most of the integrated HBV DNAs expressed X mRNA and encoded a product with trans-activation activity in spite of the loss of the 3' end region of the X gene due to integration. From cDNA cloning and sequence analysis of X mRNA transcribed from native or integrated HBV DNA, the X protein was found to be translated from the X open reading frame without splicing. For integrated HBV DNA, transcription was extended to a cellular flanking DNA and an X gene-cell fusion transcript was terminated by using a cellular poly(A) signal. The amino acid sequence deduced from an X-cell fusion transcript indicated truncation of the carboxyl-terminal five amino acids, but the upstream region of seven amino acids conserved among hepadnaviruses was retained in the integrated HBV DNA, suggesting that this conserved region is essential for the transactivation function of the X protein. These findings support the following explanation for hepatocarcinogenesis by HBV DNA integration: the expression of a cellular oncogene(s) is transactivated at the time of chronic infection by the increasing amounts of the integrated HBV gene product(s), such as the X-cell fusion product

  8. Measuring a Truncated Disk in Aquila X-1

    Science.gov (United States)

    King, Ashley L.; Tomsick, John A.; Miller, Jon M.; Chenevez, Jerome; Barret, Didier; Boggs, Steven E.; Chakrabarty, Deepto; Christensen, Finn E.; Craig, William W.; Feurst, Felix; hide

    2016-01-01

    We present NuSTAR and Swift observations of the neutron star Aquila X-1 during the peak of its 2014 July outburst. The spectrum is soft with strong evidence for a broad Fe K(alpha) line. Modeled with a relativistically broadened reflection model, we find that the inner disk is truncated with an inner radius of 15 +/- 3RG. The disk is likely truncated by either the boundary layer and/or a magnetic field. Associating the truncated inner disk with pressure from a magnetic field gives an upper limit of B < 5+/- 2x10(exp 8) G. Although the radius is truncated far from the stellar surface, material is still reaching the neutron star surface as evidenced by the X-ray burst present in the NuSTAR observation.

  9. Evolution of truncated moments of singlet parton distributions

    International Nuclear Information System (INIS)

    Forte, S.; Magnea, L.; Piccione, A.; Ridolfi, G.

    2001-01-01

    We define truncated Mellin moments of parton distributions by restricting the integration range over the Bjorken variable to the experimentally accessible subset x 0 ≤x≤1 of the allowed kinematic range 0≤x≤1. We derive the evolution equations satisfied by truncated moments in the general (singlet) case in terms of an infinite triangular matrix of anomalous dimensions which couple each truncated moment to all higher moments with orders differing by integers. We show that the evolution of any moment can be determined to arbitrarily good accuracy by truncating the system of coupled moments to a sufficiently large but finite size, and show how the equations can be solved in a way suitable for numerical applications. We discuss in detail the accuracy of the method in view of applications to precision phenomenology

  10. New truncation mutation of the NR2E3 gene in a Japanese patient with enhanced S-cone syndrome.

    Science.gov (United States)

    Kuniyoshi, Kazuki; Hayashi, Takaaki; Sakuramoto, Hiroyuki; Mishima, Hiroshi; Tsuneoka, Hiroshi; Tsunoda, Kazushige; Iwata, Takeshi; Shimomura, Yoshikazu

    2016-11-01

    The enhanced S-cone syndrome (ESCS) is a rare hereditary retinal degeneration that has enhanced short wavelength-sensitive cone (S-cone) functions. The longitudinal clinical course of this disease has been rarely reported, and the genetic aspects of ESCS have not been well investigated in the Japanese population. In this report, we present our clinical and genetic findings for 2 patients with ESCS. The patients were 2 unrelated Japanese men. Standard ophthalmic examinations and mutation screening for the NR2E3 gene were performed. Patient 1 was a 36-year-old man, and his clinical findings were typical of ESCS. His decimal best-corrected visual acuity (BCVA) was 1.0 OD and 0.5 OS after removal of cataracts. Genetic investigations revealed a homozygous truncation frameshift, the p.I307LfsX33 mutation. Patient 2 was an 11-year-old boy when he was first examined by us. His clinical findings were typical of ESCS except for uveitis in the left eye. His decimal BCVA at the age of 39 years was maintained at 1.5 in each eye, although the retinal degeneration and visual field impairments had progressed during the follow-up period. The genetic investigations revealed homozygous mutations of p.R104Q in the NR2E3 gene. The frameshift mutation, p.I307LfsX33, in the NR2E3 gene is a new causative mutation for ESCS. The clinical observations for patient 2 are the longest ever reported. The retinal degeneration caused by this mutation is slowly progressive, and these patients maintained good vision with maintenance of the foveal structure until their late thirties.

  11. Data and performance profiles applying an adaptive truncation criterion, within linesearch-based truncated Newton methods, in large scale nonconvex optimization

    Directory of Open Access Journals (Sweden)

    Andrea Caliciotti

    2018-04-01

    Full Text Available In this paper, we report data and experiments related to the research article entitled “An adaptive truncation criterion, for linesearch-based truncated Newton methods in large scale nonconvex optimization” by Caliciotti et al. [1]. In particular, in Caliciotti et al. [1], large scale unconstrained optimization problems are considered by applying linesearch-based truncated Newton methods. In this framework, a key point is the reduction of the number of inner iterations needed, at each outer iteration, to approximately solving the Newton equation. A novel adaptive truncation criterion is introduced in Caliciotti et al. [1] to this aim. Here, we report the details concerning numerical experiences over a commonly used test set, namely CUTEst (Gould et al., 2015 [2]. Moreover, comparisons are reported in terms of performance profiles (Dolan and Moré, 2002 [3], adopting different parameters settings. Finally, our linesearch-based scheme is compared with a renowned trust region method, namely TRON (Lin and Moré, 1999 [4].

  12. Selective apoptosis induction in MCF-7 cell line by truncated minimal functional region of Apoptin

    International Nuclear Information System (INIS)

    Shen Ni, Lim; Allaudin, Zeenathul Nazariah bt; Mohd Lila, Mohd Azmi b; Othman, Abas Mazni b; Othman, Fauziah bt

    2013-01-01

    Chicken Anemia Virus (CAV) VP3 protein (also known as Apoptin), a basic and proline-rich protein has a unique capability in inducing apoptosis in cancer cells but not in normal cells. Five truncated Apoptin proteins were analyzed to determine their selective ability to migrate into the nucleus of human breast adenocarcinoma MCF-7 cells for inducing apoptosis. For identification of the minimal selective domain for apoptosis, the wild-type Apoptin gene had been reconstructed by PCR to generate segmental deletions at the N’ terminal and linked with nuclear localization sites (NLS1 and NLS2). All the constructs were fused with maltose-binding protein gene and individually expressed by in vitro Rapid Translation System. Standardized dose of proteins were delivered into human breast adenocarcinoma MCF-7 cells and control human liver Chang cells by cytoplasmic microinjection, and subsequently observed for selective apoptosis effect. Three of the truncated Apoptin proteins with N-terminal deletions spanning amino acid 32–83 retained the cancer selective nature of wild-type Apoptin. The proteins were successfully translocated to the nucleus of MCF-7 cells initiating apoptosis, whereas non-toxic cytoplasmic retention was observed in normal Chang cells. Whilst these truncated proteins retained the tumour-specific death effector ability, the specificity for MCF-7 cells was lost in two other truncated proteins that harbor deletions at amino acid 1–31. The detection of apoptosing normal Chang cells and MCF-7 cells upon cytoplasmic microinjection of these proteins implicated a loss in Apoptin’s signature targeting activity. Therefore, the critical stretch spanning amino acid 1–31 at the upstream of a known hydrophobic leucine-rich stretch (LRS) was strongly suggested as one of the prerequisite region in Apoptin for cancer targeting. Identification of this selective domain provides a platform for developing small targets to facilitating carrier-mediated-transport across

  13. Conditional truncated plurigaussian simulation; Simulacao plurigaussiana truncada com condicionamento

    Energy Technology Data Exchange (ETDEWEB)

    Simon, Vitor Hugo

    1997-12-01

    The goal of this work was a development of an algorithm for the Truncated Plurigaussian Stochastic Simulation and its validation in a complex geologic model. The reservoir data comes from Aux Vases Zone at Rural Hill Field in Illinois, USA, and from the 2D geological interpretation, described by WEIMER et al. (1982), three sets of samples, with different grid densities ware taken. These sets were used to condition the simulation and to refine the estimates of the non-stationary matrix of facies proportions, used to truncate the gaussian random functions (RF). The Truncated Plurigaussian Model is an extension of the Truncated Gaussian Model (TG). In this new model its possible to use several facies with different spatial structures, associated with the simplicity of TG. The geological interpretation, used as a validation model, was chosen because it shows a set of NW/SE elongated tidal channels cutting the NE/SW shoreline deposits interleaved by impermeable facies. These characteristics of spatial structures of sedimentary facies served to evaluate the simulation model. Two independent gaussian RF were used, as well as an 'erosive model' as the truncation strategy. Also, non-conditional simulations were proceeded, using linearly combined gaussian RF with varying correlation coefficients. It was analyzed the influence of some parameters like: number of gaussian RF,correlation coefficient, truncations strategy, in the outcome of simulation, and also the physical meaning of these parameters under a geological point of view. It was showed, step by step, using an example, the theoretical model, and how to construct an algorithm to simulate with the Truncated Plurigaussian Model. The conclusion of this work was that even with a plain algorithm of the Conditional Truncated Plurigaussian and a complex geological model it's possible to obtain a usefulness product. (author)

  14. Truncation in diffraction pattern analysis. Pt. 1

    International Nuclear Information System (INIS)

    Delhez, R.; Keijser, T.H. de; Mittemeijer, E.J.; Langford, J.I.

    1986-01-01

    An evaluation of the concept of a line profile is provoked by truncation of the range of intensity measurement in practice. The measured truncated line profile can be considered either as part of the total intensity distribution which peaks at or near the reciprocal-lattice points (approach 1), or as part of a component line profile which is confined to a single reciprocal-lattice point (approach 2). Some false conceptions in line-profile analysis can then be avoided and recipes can be developed for the extrapolation of the tails of the truncated line profile. Fourier analysis of line profiles, according to the first approach, implies a Fourier series development of the total intensity distribution defined within [l - 1/2, l + 1/2] (l indicates the node considered in reciprocal space); the second approach implies a Fourier transformation of the component line profile defined within [ - ∞, + ∞]. Exact descriptions of size broadening are provided by both approaches, whereas combined size and strain broadening can only be evaluated adequately within the first approach. Straightforward methods are given for obtaining truncation-corrected values for the average crystallite size. (orig.)

  15. Truncation Depth Rule-of-Thumb for Convolutional Codes

    Science.gov (United States)

    Moision, Bruce

    2009-01-01

    In this innovation, it is shown that a commonly used rule of thumb (that the truncation depth of a convolutional code should be five times the memory length, m, of the code) is accurate only for rate 1/2 codes. In fact, the truncation depth should be 2.5 m/(1 - r), where r is the code rate. The accuracy of this new rule is demonstrated by tabulating the distance properties of a large set of known codes. This new rule was derived by bounding the losses due to truncation as a function of the code rate. With regard to particular codes, a good indicator of the required truncation depth is the path length at which all paths that diverge from a particular path have accumulated the minimum distance of the code. It is shown that the new rule of thumb provides an accurate prediction of this depth for codes of varying rates.

  16. Investigation of propagation dynamics of truncated vector vortex beams.

    Science.gov (United States)

    Srinivas, P; Perumangatt, C; Lal, Nijil; Singh, R P; Srinivasan, B

    2018-06-01

    In this Letter, we experimentally investigate the propagation dynamics of truncated vector vortex beams generated using a Sagnac interferometer. Upon focusing, the truncated vector vortex beam is found to regain its original intensity structure within the Rayleigh range. In order to explain such behavior, the propagation dynamics of a truncated vector vortex beam is simulated by decomposing it into the sum of integral charge beams with associated complex weights. We also show that the polarization of the truncated composite vector vortex beam is preserved all along the propagation axis. The experimental observations are consistent with theoretical predictions based on previous literature and are in good agreement with our simulation results. The results hold importance as vector vortex modes are eigenmodes of the optical fiber.

  17. Mutations in the voltage-gated sodium channel gene of anophelines and their association with resistance to pyrethroids - a review.

    Science.gov (United States)

    Silva, Ana Paula B; Santos, Joselita Maria M; Martins, Ademir J

    2014-10-07

    Constant and extensive use of chemical insecticides has created a selection pressure and favored resistance development in many insect species worldwide. One of the most important pyrethroid resistance mechanisms is classified as target site insensitivity, due to conformational changes in the target site that impair a proper binding of the insecticide molecule. The voltage-gated sodium channel (NaV) is the target of pyrethroids and DDT insecticides, used to control insects of medical, agricultural and veterinary importance, such as anophelines. It has been reported that the presence of a few non-silent point mutations in the NaV gene are associated with pyrethroid resistance, termed as 'kdr' (knockdown resistance) for preventing the knockdown effect of these insecticides. The presence of these mutations, as well as their effects, has been thoroughly studied in Anopheles mosquitoes. So far, kdr mutations have already been detected in at least 13 species (Anopheles gambiae, Anopheles arabiensis, Anopheles sinensis, Anopheles stephensi, Anopheles subpictus, Anopheles sacharovi, Anopheles culicifacies, Anopheles sundaicus, Anopheles aconitus, Anopheles vagus, Anopheles paraliae, Anopheles peditaeniatus and Anopheles albimanus) from populations of African, Asian and, more recently, American continents. Seven mutational variants (L1014F, L1014S, L1014C, L1014W, N1013S, N1575Y and V1010L) were described, with the highest prevalence of L1014F, which occurs at the 1014 site in NaV IIS6 domain. The increase of frequency and distribution of kdr mutations clearly shows the importance of this mechanism in the process of pyrethroid resistance. In this sense, several species-specific and highly sensitive methods have been designed in order to genotype individual mosquitoes for kdr in large scale, which may serve as important tolls for monitoring the dynamics of pyrethroid resistance in natural populations. We also briefly discuss investigations concerning the course of Plasmodium

  18. Wigner distribution function of circularly truncated light beams

    NARCIS (Netherlands)

    Bastiaans, M.J.; Nijhawan, O.P.; Gupta, A.K.; Musla, A.K.; Singh, Kehar

    1998-01-01

    Truncating a light beam is expressed as a convolution of its Wigner distribution function and the WDF of the truncating aperture. The WDF of a circular aperture is derived and an approximate expression - which is exact in the space and the spatial-frequency origin and whose integral over the spatial

  19. Scavenger receptor AI/II truncation, lung function and COPD: a large population-based study

    DEFF Research Database (Denmark)

    Thomsen, M; Nordestgaard, B G; Tybjærg-Hansen, Anne

    2011-01-01

    The scavenger receptor A-I/II (SRA-I/II) on alveolar macrophages is involved in recognition and clearance of modified lipids and inhaled particulates. A rare variant of the SRA-I/II gene, Arg293X, truncates the distal collagen-like domain, which is essential for ligand recognition. We tested...... whether the Arg293X variant is associated with reduced lung function and risk of chronic obstructive pulmonary disease (COPD) in the general population....

  20. The effect of truncation on very small cardiac SPECT camera systems

    International Nuclear Information System (INIS)

    Rohmer, Damien; Eisner, Robert L.; Gullberg, Grant T.

    2006-01-01

    Background: The limited transaxial field-of-view (FOV) of a very small cardiac SPECT camera system causes view-dependent truncation of the projection of structures exterior to, but near the heart. Basic tomographic principles suggest that the reconstruction of non-attenuated truncated data gives a distortion-free image in the interior of the truncated region, but the DC term of the Fourier spectrum of the reconstructed image is incorrect, meaning that the intensity scale of the reconstruction is inaccurate. The purpose of this study was to characterize the reconstructed image artifacts from truncated data, and to quantify their effects on the measurement of tracer uptake in the myocardial. Particular attention was given to instances where the heart wall is close to hot structures (structures of high activity uptake).Methods: The MCAT phantom was used to simulate a 2D slice of the heart region. Truncated and non-truncated projections were formed both with and without attenuation. The reconstructions were analyzed for artifacts in the myocardium caused by truncation, and for the effect that attenuation has relative to increasing those artifacts. Results: The inaccuracy due to truncation is primarily caused by an incorrect DC component. For visualizing the left ventricular wall, this error is not worse than the effect of attenuation. The addition of a small hot bowel-like structure near the left ventricle causes few changes in counts on the wall. Larger artifacts due to the truncation are located at the boundary of the truncation and can be eliminated by sinogram interpolation. Finally,algebraic reconstruction methods are shown to give better reconstruction results than an analytical filtered back-projection reconstruction algorithm. Conclusion: Small inaccuracies in reconstructed images from small FOV camera systems should have little effect on clinical interpretation. However, changes in the degree of inaccuracy in counts from slice to slice are due to changes in

  1. The investigation of the truncated mbtA gene within the mycobactin cluster of Mycobacterium avium subspecies paratuberculosis as a novel diagnostic marker for real-time PCR.

    Science.gov (United States)

    de Kruijf, Marcel; Coffey, Aidan; O'Mahony, Jim

    2017-05-01

    The inability of Mycobacterium avium subspecies paratuberculosis (MAP) to produce endogenous mycobactin in-vitro is most likely due to the presence of a truncated mbtA gene within the mycobactin cluster of MAP. The main goal of this study was to investigate this unique mbtA truncation as a potential novel PCR diagnostic marker for MAP. Novel primers were designed that were located within the truncated region and the contiguous MAP2179 gene. Primers were evaluated against non-MAP isolates and no amplicons were generated. The detection limit of this mbtA-MAP2179 target was evaluated using a range of MAP DNA concentrations, MAP inoculated faecal material and 20 MAP isolates. The performance of mbtA-MAP2179 was compared to the established f57 target. The detection limits recorded for MAP K-10 DNA and from MAP K-10 inoculated faecal samples were 0.34pg and 10 4 CFU/g respectively for both f57 and mbtA-MAP2179. A detection limit of 10 3 CFU/g was recorded for both targets, but not achieved consistently. The detection limit of MAP from inoculated faecal material was successful at 10 3 CFU/g for mbtA-MAP2179 when FAM probe real-time PCR was used. A MAP cell concentration of 10 2 CFU/g was detected successfully, but again not consistently achieved. All 20 mycobacterial isolates were successfully identified as MAP by f57 and mbtA-MAP2179. Interestingly, the mbtA-MAP2179 real-time PCR assay resulted in the formation of a unique melting curve profile that contained two melting curve peaks rather than one single peak. This melting curve phenomenon was attributed towards the asymmetrical GC% distribution within the mbtA-MAP2179 amplicon. This study investigated the implementation of the mbtA-MAP2179 target as a novel diagnostic marker and the detection limits obtained with mbtA-MAP2179 were comparable to the established f57 target, making the mbtA-MAP2179 an adequate confirmatory target. Moreover, the mbtA-MAP2179 target could be implemented in multiplex real-time PCR assays and

  2. Flexible scheme to truncate the hierarchy of pure states.

    Science.gov (United States)

    Zhang, P-P; Bentley, C D B; Eisfeld, A

    2018-04-07

    The hierarchy of pure states (HOPS) is a wavefunction-based method that can be used for numerically modeling open quantum systems. Formally, HOPS recovers the exact system dynamics for an infinite depth of the hierarchy. However, truncation of the hierarchy is required to numerically implement HOPS. We want to choose a "good" truncation method, where by "good" we mean that it is numerically feasible to check convergence of the results. For the truncation approximation used in previous applications of HOPS, convergence checks are numerically challenging. In this work, we demonstrate the application of the "n-particle approximation" to HOPS. We also introduce a new approximation, which we call the "n-mode approximation." We then explore the convergence of these truncation approximations with respect to the number of equations required in the hierarchy in two exemplary problems: absorption and energy transfer of molecular aggregates.

  3. Flexible scheme to truncate the hierarchy of pure states

    Science.gov (United States)

    Zhang, P.-P.; Bentley, C. D. B.; Eisfeld, A.

    2018-04-01

    The hierarchy of pure states (HOPS) is a wavefunction-based method that can be used for numerically modeling open quantum systems. Formally, HOPS recovers the exact system dynamics for an infinite depth of the hierarchy. However, truncation of the hierarchy is required to numerically implement HOPS. We want to choose a "good" truncation method, where by "good" we mean that it is numerically feasible to check convergence of the results. For the truncation approximation used in previous applications of HOPS, convergence checks are numerically challenging. In this work, we demonstrate the application of the "n-particle approximation" to HOPS. We also introduce a new approximation, which we call the "n-mode approximation." We then explore the convergence of these truncation approximations with respect to the number of equations required in the hierarchy in two exemplary problems: absorption and energy transfer of molecular aggregates.

  4. A truncated Kv1.1 protein in the brain of the megencephaly mouse: expression and interaction

    Directory of Open Access Journals (Sweden)

    Århem Peter

    2005-11-01

    Full Text Available Abstract Background The megencephaly mouse, mceph/mceph, is epileptic and displays a dramatically increased brain volume and neuronal count. The responsible mutation was recently revealed to be an eleven base pair deletion, leading to a frame shift, in the gene encoding the potassium channel Kv1.1. The predicted MCEPH protein is truncated at amino acid 230 out of 495. Truncated proteins are usually not expressed since nonsense mRNAs are most often degraded. However, high Kv1.1 mRNA levels in mceph/mceph brain indicated that it escaped this control mechanism. Therefore, we hypothesized that the truncated Kv1.1 would be expressed and dysregulate other Kv1 subunits in the mceph/mceph mice. Results We found that the MCEPH protein is expressed in the brain of mceph/mceph mice. MCEPH was found to lack mature (Golgi glycosylation, but to be core glycosylated and trapped in the endoplasmic reticulum (ER. Interactions between MCEPH and other Kv1 subunits were studied in cell culture, Xenopus oocytes and the brain. MCEPH can form tetramers with Kv1.1 in cell culture and has a dominant negative effect on Kv1.2 and Kv1.3 currents in oocytes. However, it does not retain Kv1.2 in the ER of neurons. Conclusion The megencephaly mice express a truncated Kv1.1 in the brain, and constitute a unique tool to study Kv1.1 trafficking relevant for understanding epilepsy, ataxia and pathologic brain overgrowth.

  5. Truncated predictor feedback for time-delay systems

    CERN Document Server

    Zhou, Bin

    2014-01-01

    This book provides a systematic approach to the design of predictor based controllers for (time-varying) linear systems with either (time-varying) input or state delays. Differently from those traditional predictor based controllers, which are infinite-dimensional static feedback laws and may cause difficulties in their practical implementation, this book develops a truncated predictor feedback (TPF) which involves only finite dimensional static state feedback. Features and topics: A novel approach referred to as truncated predictor feedback for the stabilization of (time-varying) time-delay systems in both the continuous-time setting and the discrete-time setting is built systematically Semi-global and global stabilization problems of linear time-delay systems subject to either magnitude saturation or energy constraints are solved in a systematic manner Both stabilization of a single system and consensus of a group of systems (multi-agent systems) are treated in a unified manner by applying the truncated pre...

  6. Maltose binding protein-fusion enhances the bioactivity of truncated forms of pig myostatin propeptide produced in E. coli.

    Directory of Open Access Journals (Sweden)

    Sang Beum Lee

    Full Text Available Myostatin (MSTN is a potent negative regulator of skeletal muscle growth. MSTN propeptide (MSTNpro inhibits MSTN binding to its receptor through complex formation with MSTN, implying that MSTNpro can be a useful agent to improve skeletal muscle growth in meat-producing animals. Four different truncated forms of pig MSTNpro containing N-terminal maltose binding protein (MBP as a fusion partner were expressed in E. coli, and purified by the combination of affinity chromatography and gel filtration. The MSTN-inhibitory capacities of these proteins were examined in an in vitro gene reporter assay. A MBP-fused, truncated MSTNpro containing residues 42-175 (MBP-Pro42-175 exhibited the same MSTN-inhibitory potency as the full sequence MSTNpro. Truncated MSTNpro proteins containing either residues 42-115 (MBP-Pro42-115 or 42-98 (MBP-Pro42-98 also exhibited MSTN-inhibitory capacity even though the potencies were significantly lower than that of full sequence MSTNpro. In pull-down assays, MBP-Pro42-175, MBP-Pro42-115, and MBP-Pro42-98 demonstrated their binding to MSTN. MBP was removed from the truncated MSTNpro proteins by incubation with factor Xa to examine the potential role of MBP on MSTN-inhibitory capacity of those proteins. Removal of MBP from MBP-Pro42-175 and MBP-Pro42-98 resulted in 20-fold decrease in MSTN-inhibitory capacity of Pro42-175 and abolition of MSTN-inhibitory capacity of Pro42-98, indicating that MBP as fusion partner enhanced the MSTN-inhibitory capacity of those truncated MSTNpro proteins. In summary, this study shows that MBP is a very useful fusion partner in enhancing MSTN-inhibitory potency of truncated forms of MSTNpro proteins, and MBP-fused pig MSTNpro consisting of amino acid residues 42-175 is sufficient to maintain the full MSTN-inhibitory capacity.

  7. Truncating variants in the majority of the cytoplasmic domain of PCDH15 are unlikely to cause Usher syndrome 1F.

    Science.gov (United States)

    Perreault-Micale, Cynthia; Frieden, Alexander; Kennedy, Caleb J; Neitzel, Dana; Sullivan, Jessica; Faulkner, Nicole; Hallam, Stephanie; Greger, Valerie

    2014-11-01

    Loss of function variants in the PCDH15 gene can cause Usher syndrome type 1F, an autosomal recessive disease associated with profound congenital hearing loss, vestibular dysfunction, and retinitis pigmentosa. The Ashkenazi Jewish population has an increased incidence of Usher syndrome type 1F (founder variant p.Arg245X accounts for 75% of alleles), yet the variant spectrum in a panethnic population remains undetermined. We sequenced the coding region and intron-exon borders of PCDH15 using next-generation DNA sequencing technology in approximately 14,000 patients from fertility clinics. More than 600 unique PCDH15 variants (single nucleotide changes and small indels) were identified, including previously described pathogenic variants p.Arg3X, p.Arg245X (five patients), p.Arg643X, p.Arg929X, and p.Arg1106X. Novel truncating variants were also found, including one in the N-terminal extracellular domain (p.Leu877X), but all other novel truncating variants clustered in the exon 33 encoded C-terminal cytoplasmic domain (52 patients, 14 variants). One variant was observed predominantly in African Americans (carrier frequency of 2.3%). The high incidence of truncating exon 33 variants indicates that they are unlikely to cause Usher syndrome type 1F even though many remove a large portion of the gene. They may be tolerated because PCDH15 has several alternate cytoplasmic domain exons and differentially spliced isoforms may function redundantly. Effects of some PCDH15 truncating variants were addressed by deep sequencing of a panethnic population. Copyright © 2014 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

  8. A natural mutation-led truncation in one of the two aluminum-activated malate transporter-like genes at the Ma locus is associated with low fruit acidity in apple.

    Science.gov (United States)

    Bai, Yang; Dougherty, Laura; Li, Mingjun; Fazio, Gennaro; Cheng, Lailiang; Xu, Kenong

    2012-08-01

    Acidity levels greatly affect the taste and flavor of fruit, and consequently its market value. In mature apple fruit, malic acid is the predominant organic acid. Several studies have confirmed that the major quantitative trait locus Ma largely controls the variation of fruit acidity levels. The Ma locus has recently been defined in a region of 150 kb that contains 44 predicted genes on chromosome 16 in the Golden Delicious genome. In this study, we identified two aluminum-activated malate transporter-like genes, designated Ma1 and Ma2, as strong candidates of Ma by narrowing down the Ma locus to 65-82 kb containing 12-19 predicted genes depending on the haplotypes. The Ma haplotypes were determined by sequencing two bacterial artificial chromosome clones from G.41 (an apple rootstock of genotype Mama) that cover the two distinct haplotypes at the Ma locus. Gene expression profiling in 18 apple germplasm accessions suggested that Ma1 is the major determinant at the Ma locus controlling fruit acidity as Ma1 is expressed at a much higher level than Ma2 and the Ma1 expression is significantly correlated with fruit titratable acidity (R (2) = 0.4543, P = 0.0021). In the coding sequences of low acidity alleles of Ma1 and Ma2, sequence variations at the amino acid level between Golden Delicious and G.41 were not detected. But the alleles for high acidity vary considerably between the two genotypes. The low acidity allele of Ma1, Ma1-1455A, is mainly characterized by a mutation at base 1455 in the open reading frame. The mutation leads to a premature stop codon that truncates the carboxyl terminus of Ma1-1455A by 84 amino acids compared with Ma1-1455G. A survey of 29 apple germplasm accessions using marker CAPS(1455) that targets the SNP(1455) in Ma1 showed that the CAPS(1455A) allele was associated completely with high pH and highly with low titratable acidity, suggesting that the natural mutation-led truncation is most likely responsible for the abolished function of Ma

  9. New results to BDD truncation method for efficient top event probability calculation

    International Nuclear Information System (INIS)

    Mo, Yuchang; Zhong, Farong; Zhao, Xiangfu; Yang, Quansheng; Cui, Gang

    2012-01-01

    A Binary Decision Diagram (BDD) is a graph-based data structure that calculates an exact top event probability (TEP). It has been a very difficult task to develop an efficient BDD algorithm that can solve a large problem since its memory consumption is very high. Recently, in order to solve a large reliability problem within limited computational resources, Jung presented an efficient method to maintain a small BDD size by a BDD truncation during a BDD calculation. In this paper, it is first identified that Jung's BDD truncation algorithm can be improved for a more practical use. Then, a more efficient truncation algorithm is proposed in this paper, which can generate truncated BDD with smaller size and approximate TEP with smaller truncation error. Empirical results showed this new algorithm uses slightly less running time and slightly more storage usage than Jung's algorithm. It was also found, that designing a truncation algorithm with ideal features for every possible fault tree is very difficult, if not impossible. The so-called ideal features of this paper would be that with the decrease of truncation limits, the size of truncated BDD converges to the size of exact BDD, but should never be larger than exact BDD.

  10. Maximum nondiffracting propagation distance of aperture-truncated Airy beams

    Science.gov (United States)

    Chu, Xingchun; Zhao, Shanghong; Fang, Yingwu

    2018-05-01

    Airy beams have called attention of many researchers due to their non-diffracting, self-healing and transverse accelerating properties. A key issue in research of Airy beams and its applications is how to evaluate their nondiffracting propagation distance. In this paper, the critical transverse extent of physically realizable Airy beams is analyzed under the local spatial frequency methodology. The maximum nondiffracting propagation distance of aperture-truncated Airy beams is formulated and analyzed based on their local spatial frequency. The validity of the formula is verified by comparing the maximum nondiffracting propagation distance of an aperture-truncated ideal Airy beam, aperture-truncated exponentially decaying Airy beam and exponentially decaying Airy beam. Results show that the formula can be used to evaluate accurately the maximum nondiffracting propagation distance of an aperture-truncated ideal Airy beam. Therefore, it can guide us to select appropriate parameters to generate Airy beams with long nondiffracting propagation distance that have potential application in the fields of laser weapons or optical communications.

  11. An iterative reconstruction from truncated projection data

    International Nuclear Information System (INIS)

    Anon.

    1985-01-01

    Various methods have been proposed for tomographic reconstruction from truncated projection data. In this paper, a reconstructive method is discussed which consists of iterations of filtered back-projection, reprojection and some nonlinear processings. First, the method is so constructed that it converges to a fixed point. Then, to examine its effectiveness, comparisons are made by computer experiments with two existing reconstructive methods for truncated projection data, that is, the method of extrapolation based on the smooth assumption followed by filtered back-projection, and modified additive ART

  12. Production of biodiesel by transesterification of corn and soybean oils with ethanol or butanol using resin-bound truncated Candida antarctica lipase B

    Science.gov (United States)

    Enzymatic catalysts, such as lipases, have advantages over chemical catalysts for transesterification of triglycerides to produce biodiesel. A gene encoding a synthetic truncated Candida antarctica lipase B (CALB) was generated via automated PCR and expressed in Saccharomyces cerevisiae. Western b...

  13. Amino substituted nitrogen heterocycle ureas as kinase insert domain containing receptor (KDR inhibitors: Performance of structure–activity relationship approaches

    Directory of Open Access Journals (Sweden)

    Hayriye Yilmaz

    2015-06-01

    Full Text Available A quantitative structure–activity relationship (QSAR study was performed on a set of amino-substituted nitrogen heterocyclic urea derivatives. Two novel approaches were applied: (1 the simplified molecular input-line entry systems (SMILES based optimal descriptors approach; and (2 the fragment-based simplex representation of molecular structure (SiRMS approach. Comparison with the classic scheme of building up the model and balance of correlation (BC for optimal descriptors approach shows that the BC scheme provides more robust predictions than the classic scheme for the considered pIC50 of the heterocyclic urea derivatives. Comparison of the SMILES-based optimal descriptors and SiRMS approaches has confirmed good performance of both techniques in prediction of kinase insert domain containing receptor (KDR inhibitory activity, expressed as a logarithm of inhibitory concentration (pIC50 of studied compounds.

  14. Truncated Wigner dynamics and conservation laws

    Science.gov (United States)

    Drummond, Peter D.; Opanchuk, Bogdan

    2017-10-01

    Ultracold Bose gases can be used to experimentally test many-body theory predictions. Here we point out that both exact conservation laws and dynamical invariants exist in the topical case of the one-dimensional Bose gas, and these provide an important validation of methods. We show that the first four quantum conservation laws are exactly conserved in the approximate truncated Wigner approach to many-body quantum dynamics. Center-of-mass position variance is also exactly calculable. This is nearly exact in the truncated Wigner approximation, apart from small terms that vanish as N-3 /2 as N →∞ with fixed momentum cutoff. Examples of this are calculated in experimentally relevant, mesoscopic cases.

  15. Inference for shared-frailty survival models with left-truncated data

    NARCIS (Netherlands)

    van den Berg, G.J.; Drepper, B.

    2016-01-01

    Shared-frailty survival models specify that systematic unobserved determinants of duration outcomes are identical within groups of individuals. We consider random-effects likelihood-based statistical inference if the duration data are subject to left-truncation. Such inference with left-truncated

  16. GLP-1 (glucagon-like peptide 1) and truncated GLP-1, fragments of human proglucagon, inhibit gastric acid secretion in humans

    DEFF Research Database (Denmark)

    Schjoldager, B T; Mortensen, P E; Christiansen, J

    1989-01-01

    Glucagon-like peptide 1 amide (GLP-1 amide), a predicted product of the glucagon gene (proglucagon 72-107-amide), and truncated GLP-1 (proglucagon 78-107-amide), recently isolated from porcine small intestine, were infused in doses of 100 and 400 ng/kg/hr and 12.5 and 50 ng/kg/hr, respectively...

  17. Truncated ALK derived from chromosomal translocation t(2;5)(p23;q35) binds to the SH3 domain of p85-PI3K.

    Science.gov (United States)

    Polgar, Doris; Leisser, Christina; Maier, Susanne; Strasser, Stephan; Rüger, Beate; Dettke, Markus; Khorchide, Maya; Simonitsch, Ingrid; Cerni, Christa; Krupitza, Georg

    2005-02-15

    The chromosomal translocation t(2;5)(p23;q35) is associated with "Anaplastic large cell lymphomas" (ALCL), a Non Hodgkin Lymphoma occurring in childhood. The fusion of the tyrosine kinase gene-ALK (anaplastic lymphoma kinase) on chromosome 2p23 to the NPM (nucleophosmin/B23) gene on chromosome 5q35 results in a 80 kDa chimeric protein, which activates the "survival" kinase PI3K. However, the binding mechanism between truncated ALK and PI3K is poorly understood. Therefore, we attempted to elucidate the molecular interaction between ALK and the regulatory p85 subunit of PI3K. Here we provide evidence that the truncated ALK homodimer binds to the SH3 domain of p85. This finding may be useful for the development of a new target-specific intervention.

  18. Immature truncated O-glycophenotype of cancer directly induces oncogenic features

    DEFF Research Database (Denmark)

    Radhakrishnan, Prakash; Dabelsteen, Sally; Madsen, Frey Brus

    2014-01-01

    Aberrant expression of immature truncated O-glycans is a characteristic feature observed on virtually all epithelial cancer cells, and a very high frequency is observed in early epithelial premalignant lesions that precede the development of adenocarcinomas. Expression of the truncated O-glycan s...

  19. Probability distributions with truncated, log and bivariate extensions

    CERN Document Server

    Thomopoulos, Nick T

    2018-01-01

    This volume presents a concise and practical overview of statistical methods and tables not readily available in other publications. It begins with a review of the commonly used continuous and discrete probability distributions. Several useful distributions that are not so common and less understood are described with examples and applications in full detail: discrete normal, left-partial, right-partial, left-truncated normal, right-truncated normal, lognormal, bivariate normal, and bivariate lognormal. Table values are provided with examples that enable researchers to easily apply the distributions to real applications and sample data. The left- and right-truncated normal distributions offer a wide variety of shapes in contrast to the symmetrically shaped normal distribution, and a newly developed spread ratio enables analysts to determine which of the three distributions best fits a particular set of sample data. The book will be highly useful to anyone who does statistical and probability analysis. This in...

  20. Germline RAD51B truncating mutation in a family with cutaneous melanoma

    DEFF Research Database (Denmark)

    Wadt, Karin A W; Aoude, Lauren G; Golmard, Lisa

    2015-01-01

    Known melanoma predisposition genes only account for around 40% of high-density melanoma families. Other rare mutations are likely to play a role in melanoma predisposition. RAD51B plays an important role in DNA repair through homologous recombination, and inactivation of RAD51B has been implicated...... in tumorigenesis. Thus RAD51B is a good candidate melanoma susceptibility gene, and previously, a germline splicing mutation in RAD51B has been identified in a family with early-onset breast cancer. In order to find genetic variants associated with melanoma predisposition, whole-exome sequencing was carried out...... on blood samples from a three-case cutaneous melanoma family. We identified a novel germline RAD51B nonsense mutation, and we demonstrate reduced expression of RAD51B in melanoma cells indicating inactivation of RAD51B. This is only the second report of a germline truncating RAD51B mutation. While...

  1. Impact of degree truncation on the spread of a contagious process on networks.

    Science.gov (United States)

    Harling, Guy; Onnela, Jukka-Pekka

    2018-03-01

    Understanding how person-to-person contagious processes spread through a population requires accurate information on connections between population members. However, such connectivity data, when collected via interview, is often incomplete due to partial recall, respondent fatigue or study design, e.g., fixed choice designs (FCD) truncate out-degree by limiting the number of contacts each respondent can report. Past research has shown how FCD truncation affects network properties, but its implications for predicted speed and size of spreading processes remain largely unexplored. To study the impact of degree truncation on predictions of spreading process outcomes, we generated collections of synthetic networks containing specific properties (degree distribution, degree-assortativity, clustering), and also used empirical social network data from 75 villages in Karnataka, India. We simulated FCD using various truncation thresholds and ran a susceptible-infectious-recovered (SIR) process on each network. We found that spreading processes propagated on truncated networks resulted in slower and smaller epidemics, with a sudden decrease in prediction accuracy at a level of truncation that varied by network type. Our results have implications beyond FCD to truncation due to any limited sampling from a larger network. We conclude that knowledge of network structure is important for understanding the accuracy of predictions of process spread on degree truncated networks.

  2. Application of a truncated normal failure distribution in reliability testing

    Science.gov (United States)

    Groves, C., Jr.

    1968-01-01

    Statistical truncated normal distribution function is applied as a time-to-failure distribution function in equipment reliability estimations. Age-dependent characteristics of the truncated function provide a basis for formulating a system of high-reliability testing that effectively merges statistical, engineering, and cost considerations.

  3. Truncation scheme of time-dependent density-matrix approach II

    Energy Technology Data Exchange (ETDEWEB)

    Tohyama, Mitsuru [Kyorin University School of Medicine, Mitaka, Tokyo (Japan); Schuck, Peter [Institut de Physique Nucleaire, IN2P3-CNRS, Universite Paris-Sud, Orsay (France); Laboratoire de Physique et de Modelisation des Milieux Condenses, CNRS et Universite Joseph Fourier, Grenoble (France)

    2017-09-15

    A truncation scheme of the Bogoliubov-Born-Green-Kirkwood-Yvon hierarchy for reduced density matrices, where a three-body density matrix is approximated by two-body density matrices, is improved to take into account a normalization effect. The truncation scheme is tested for the Lipkin model. It is shown that the obtained results are in good agreement with the exact solutions. (orig.)

  4. Multiple-scattering theory with a truncated basis set

    International Nuclear Information System (INIS)

    Zhang, X.; Butler, W.H.

    1992-01-01

    Multiple-scattering theory (MST) is an extremely efficient technique for calculating the electronic structure of an assembly of atoms. The wave function in MST is expanded in terms of spherical waves centered on each atom and indexed by their orbital and azimuthal quantum numbers, l and m. The secular equation which determines the characteristic energies can be truncated at a value of the orbital angular momentum l max , for which the higher angular momentum phase shifts, δ l (l>l max ), are sufficiently small. Generally, the wave-function coefficients which are calculated from the secular equation are also truncated at l max . Here we point out that this truncation of the wave function is not necessary and is in fact inconsistent with the truncation of the secular equation. A consistent procedure is described in which the states with higher orbital angular momenta are retained but with their phase shifts set to zero. We show that this treatment gives smooth, continuous, and correctly normalized wave functions and that the total charge density calculated from the corresponding Green function agrees with the Lloyd formula result. We also show that this augmented wave function can be written as a linear combination of Andersen's muffin-tin orbitals in the case of muffin-tin potentials, and can be used to generalize the muffin-tin orbital idea to full-cell potentals

  5. Acute intermittent porphyria: A single-base deletion and a nonsense mutation in the human hydroxymethylbilane synthase gene, predicting truncations of the enzyme polypeptide

    Energy Technology Data Exchange (ETDEWEB)

    Lee, G.L.; Astrin, K.H.; Desnick, R.J. [Mount Sinai School of Medicine, New York, NY (United States)

    1995-08-28

    Acute intermittent porphyria (AIP) is an autosomal-dominant inborn error of metabolism that results from the half-normal activity of the third enzyme in the heme biosynthetic pathway, hydroxymethylbilane synthase (HMB-synthase). AIP is an ecogenetic condition, since the life-threatening acute attacks are precipitated by various factors, including drugs, alcohol, fasting, and certain hormones. Biochemical diagnosis is problematic, and the identification of mutations in the HMB-synthase gene provides accurate detection of presymptomatic heterozygotes, permitting avoidance of the acute precipitating factors. By direct solid-phase sequencing, two mutations causing AIP were identified, an adenine deletion at position 629 in exon 11(629delA), which alters the reading frame and predicts premature truncation of the enzyme protein after amino acid 255, and a nonsense mutation in exon 12 (R225X). These mutations were confirmed by either restriction enzyme analysis or family studies of symptomatic patients, permitting accurate presymptomatic diagnosis of affected relatives. 29 refs., 2 figs.

  6. Importance-truncated shell model for multi-shell valence spaces

    Energy Technology Data Exchange (ETDEWEB)

    Stumpf, Christina; Vobig, Klaus; Roth, Robert [Institut fuer Kernphysik, TU Darmstadt (Germany)

    2016-07-01

    The valence-space shell model is one of the work horses in nuclear structure theory. In traditional applications, shell-model calculations are carried out using effective interactions constructed in a phenomenological framework for rather small valence spaces, typically spanned by one major shell. We improve on this traditional approach addressing two main aspects. First, we use new effective interactions derived in an ab initio approach and, thus, establish a connection to the underlying nuclear interaction providing access to single- and multi-shell valence spaces. Second, we extend the shell model to larger valence spaces by applying an importance-truncation scheme based on a perturbative importance measure. In this way, we reduce the model space to the relevant basis states for the description of a few target eigenstates and solve the eigenvalue problem in this physics-driven truncated model space. In particular multi-shell valence spaces are not tractable otherwise. We combine the importance-truncated shell model with refined extrapolation schemes to approximately recover the exact result. We present first results obtained in the importance-truncated shell model with the newly derived ab initio effective interactions for multi-shell valence spaces, e.g., the sdpf shell.

  7. Flow equation of quantum Einstein gravity in a higher-derivative truncation

    International Nuclear Information System (INIS)

    Lauscher, O.; Reuter, M.

    2002-01-01

    Motivated by recent evidence indicating that quantum Einstein gravity (QEG) might be nonperturbatively renormalizable, the exact renormalization group equation of QEG is evaluated in a truncation of theory space which generalizes the Einstein-Hilbert truncation by the inclusion of a higher-derivative term (R 2 ). The beta functions describing the renormalization group flow of the cosmological constant, Newton's constant, and the R 2 coupling are computed explicitly. The fixed point properties of the 3-dimensional flow are investigated, and they are confronted with those of the 2-dimensional Einstein-Hilbert flow. The non-Gaussian fixed point predicted by the latter is found to generalize to a fixed point on the enlarged theory space. In order to test the reliability of the R 2 truncation near this fixed point we analyze the residual scheme dependence of various universal quantities; it turns out to be very weak. The two truncations are compared in detail, and their numerical predictions are found to agree with a surprisingly high precision. Because of the consistency of the results it appears increasingly unlikely that the non-Gaussian fixed point is an artifact of the truncation. If it is present in the exact theory QEG is probably nonperturbatively renormalizable and ''asymptotically safe.'' We discuss how the conformal factor problem of Euclidean gravity manifests itself in the exact renormalization group approach and show that, in the R 2 truncation, the investigation of the fixed point is not afflicted with this problem. Also the Gaussian fixed point of the Einstein-Hilbert truncation is analyzed; it turns out that it does not generalize to a corresponding fixed point on the enlarged theory space

  8. Approximate truncation robust computed tomography—ATRACT

    International Nuclear Information System (INIS)

    Dennerlein, Frank; Maier, Andreas

    2013-01-01

    We present an approximate truncation robust algorithm to compute tomographic images (ATRACT). This algorithm targets at reconstructing volumetric images from cone-beam projections in scenarios where these projections are highly truncated in each dimension. It thus facilitates reconstructions of small subvolumes of interest, without involving prior knowledge about the object. Our method is readily applicable to medical C-arm imaging, where it may contribute to new clinical workflows together with a considerable reduction of x-ray dose. We give a detailed derivation of ATRACT that starts from the conventional Feldkamp filtered-backprojection algorithm and that involves, as one component, a novel original formula for the inversion of the two-dimensional Radon transform. Discretization and numerical implementation are discussed and reconstruction results from both, simulated projections and first clinical data sets are presented. (paper)

  9. Stellar Disk Truncations: HI Density and Dynamics

    Science.gov (United States)

    Trujillo, Ignacio; Bakos, Judit

    2010-06-01

    Using HI Nearby Galaxy Survey (THINGS) 21-cm observations of a sample of nearby (nearly face-on) galaxies we explore whether the stellar disk truncation phenomenon produces any signature either in the HI gas density and/or in the gas dynamics. Recent cosmological simulations suggest that the origin of the break on the surface brightness distribution is produced by the appearance of a warp at the truncation position. This warp should produce a flaring on the gas distribution increasing the velocity dispersion of the HI component beyond the break. We do not find, however, any evidence of this increase in the gas velocity dispersion profile.

  10. Expression and characterization of truncated human heme oxygenase (hHO-1) and a fusion protein of hHO-1 with human cytochrome P450 reductase.

    Science.gov (United States)

    Wilks, A; Black, S M; Miller, W L; Ortiz de Montellano, P R

    1995-04-04

    A human heme oxygenase (hHO-1) gene without the sequence coding for the last 23 amino acids has been expressed in Escherichia coli behind the pho A promoter. The truncated enzyme is obtained in high yields as a soluble, catalytically-active protein, making it available for the first time for detailed mechanistic studies. The purified, truncated hHO-1/heme complex is spectroscopically indistinguishable from that of the rat enzyme and converts heme to biliverdin when reconstituted with rat liver cytochrome P450 reductase. A self-sufficient heme oxygenase system has been obtained by fusing the truncated hHO-1 gene to the gene for human cytochrome P450 reductase without the sequence coding for the 20 amino acid membrane binding domain. Expression of the fusion protein in pCWori+ yields a protein that only requires NADPH for catalytic turnover. The failure of exogenous cytochrome P450 reductase to stimulate turnover and the insensitivity of the catalytic rate toward changes in ionic strength establish that electrons are transferred intramolecularly between the reductase and heme oxygenase domains of the fusion protein. The Vmax for the fusion protein is 2.5 times higher than that for the reconstituted system. Therefore, either the covalent tether does not interfere with normal docking and electron transfer between the flavin and heme domains or alternative but equally efficient electron transfer pathways are available that do not require specific docking.

  11. USH1G with unique retinal findings caused by a novel truncating mutation identified by genome-wide linkage analysis

    Science.gov (United States)

    Taibah, Khalid; Bin-Khamis, Ghada; Kennedy, Shelley; Hemidan, Amal; Al-Qahtani, Faisal; Tabbara, Khalid; Mubarak, Bashayer Al; Ramzan, Khushnooda; Meyer, Brian F.; Al-Owain, Mohammed

    2012-01-01

    Purpose Usher syndrome (USH) is an autosomal recessive disorder divided into three distinct clinical subtypes based on the severity of the hearing loss, manifestation of vestibular dysfunction, and the age of onset of retinitis pigmentosa and visual symptoms. To date, mutations in seven different genes have been reported to cause USH type 1 (USH1), the most severe form. Patients diagnosed with USH1 are known to be ideal candidates to benefit from cochlear implantation. Methods Genome-wide linkage analysis using Affymetrix GeneChip Human Mapping 10K arrays were performed in three cochlear implanted Saudi siblings born from a consanguineous marriage, clinically diagnosed with USH1 by comprehensive clinical, audiological, and ophthalmological examinations. From the linkage results, the USH1G gene was screened for mutations by direct sequencing of the coding exons. Results We report the identification of a novel p.S243X truncating mutation in USH1G that segregated with the disease phenotype and was not present in 300 ethnically matched normal controls. We also report on the novel retinal findings and the outcome of cochlear implantation in the affected individuals. Conclusions In addition to reporting a novel truncating mutation, this report expands the retinal phenotype in USH1G and presents the first report of successful cochlear implants in this disease. PMID:22876113

  12. Enhancing propagation characteristics of truncated localized waves in silica

    KAUST Repository

    Salem, Mohamed

    2011-07-01

    The spectral characteristics of truncated Localized Waves propagating in dispersive silica are analyzed. Numerical experiments show that the immunity of the truncated Localized Waves propagating in dispersive silica to decay and distortion is enhanced as the non-linearity of the relation between the transverse spatial spectral components and the wave vector gets stronger, in contrast to free-space propagating waves, which suffer from early decay and distortion. © 2011 IEEE.

  13. Truncation of CPC solar collectors and its effect on energy collection

    Science.gov (United States)

    Carvalho, M. J.; Collares-Pereira, M.; Gordon, J. M.; Rabl, A.

    1985-01-01

    Analytic expressions are derived for the angular acceptance function of two-dimensional compound parabolic concentrator solar collectors (CPC's) of arbitrary degree of truncation. Taking into account the effect of truncation on both optical and thermal losses in real collectors, the increase in monthly and yearly collectible energy is also evaluated. Prior analyses that have ignored the correct behavior of the angular acceptance function at large angles for truncated collectors are shown to be in error by 0-2 percent in calculations of yearly collectible energy for stationary collectors.

  14. Identification of a truncated splice variant of IL-18 receptor alpha in the human and rat, with evidence of wider evolutionary conservation

    Directory of Open Access Journals (Sweden)

    Chris S. Booker

    2014-09-01

    Full Text Available Interleukin-18 (IL-18 is a pro-inflammatory cytokine which stimulates activation of the nuclear factor kappa beta (NF-κB pathway via interaction with the IL-18 receptor. The receptor itself is formed from a dimer of two subunits, with the ligand-binding IL-18Rα subunit being encoded by the IL18R1 gene. A splice variant of murine IL18r1, which has been previously described, is formed by transcription of an unspliced intron (forming a ‘type II’ IL18r1 transcript and is predicted to encode a receptor with a truncated intracellular domain lacking the capacity to generate downstream signalling. In order to examine the relevance of this finding to human IL-18 function, we assessed the presence of a homologous transcript by reverse transcription-polymerase chain reaction (RT-PCR in the human and rat as another common laboratory animal. We present evidence for type II IL18R1 transcripts in both species. While the mouse and rat transcripts are predicted to encode a truncated receptor with a novel 5 amino acid C-terminal domain, the human sequence is predicted to encode a truncated protein with a novel 22 amino acid sequence bearing resemblance to the ‘Box 1’ motif of the Toll/interleukin-1 receptor (TIR domain, in a similar fashion to the inhibitory interleukin-1 receptor 2. Given that transcripts from these three species are all formed by inclusion of homologous unspliced intronic regions, an analysis of homologous introns across a wider array of 33 species with available IL18R1 gene records was performed, which suggests similar transcripts may encode truncated type II IL-18Rα subunits in other species. This splice variant may represent a conserved evolutionary mechanism for regulating IL-18 activity.

  15. Enhanced cell surface expression, immunogenicity and genetic stability resulting from a spontaneous truncation of HIV Env expressed by a recombinant MVA

    International Nuclear Information System (INIS)

    Wyatt, Linda S.; Belyakov, Igor M.; Earl, Patricia L.; Berzofsky, Jay A.; Moss, Bernard

    2008-01-01

    During propagation of modified vaccinia virus Ankara (MVA) encoding HIV 89.6 Env, a few viral foci stained very prominently. Virus cloned from such foci replicated to higher titers than the parent and displayed enhanced genetic stability on passage. Sequence analysis showed a single nucleotide deletion in the 89.6 env gene of the mutant that caused a frame shift and truncation of 115 amino acids from the cytoplasmic domain. The truncated Env was more highly expressed on the cell surface, induced higher antibody responses than the full-length Env, reacted with HIV neutralizing monoclonal antibodies and mediated CD4/co-receptor-dependent fusion. Intramuscular (IM), intradermal (ID) needleless, and intrarectal (IR) catheter inoculations gave comparable serum IgG responses. However, intraoral (IO) needleless injector route gave the highest IgA in lung washings and IR gave the highest IgA and IgG responses in fecal extracts. Induction of CTL responses in the spleens of individual mice as assayed by intracellular cytokine staining was similar with both the full-length and truncated Env constructs. Induction of acute and memory CTL in the spleens of mice immunized with the truncated Env construct by ID, IO, and IR routes was comparable and higher than by the IM route, but only the IR route induced CTL in the gut-associated lymphoid tissue. Thus, truncation of Env enhanced genetic stability as well as serum and mucosal antibody responses, suggesting the desirability of a similar modification in MVA-based candidate HIV vaccines

  16. Transiently truncated and differentially regulated expression of midkine during mouse embryogenesis

    International Nuclear Information System (INIS)

    Chen Qin; Yuan Yuanyang; Lin Shuibin; Chang Youde; Zhuo Xinming; Wei Wei; Tao Ping; Ruan Lingjuan; Li Qifu; Li Zhixing

    2005-01-01

    Midkine (MK) is a retinoic acid response cytokine, mostly expressed in embryonic tissues. Aberrant expression of MK was found in numerous cancers. In human, a truncated MK was expressed specifically in tumor/cancer tissues. Here we report the discovery of a novel truncated form of MK transiently expressed during normal mouse embryonic development. In addition, MK is concentrated at the interface between developing epithelium and mesenchyme as well as highly proliferating cells. Its expression, which is closely coordinated with angiogenesis and vasculogenesis, is spatiotemporally regulated with peaks in extensive organogenesis period and undifferentiated cells tailing off in maturing cells, implying its role in nascent blood vessel (endothelial) signaling of tissue differentiation and stem cell renewal/differentiation.. Cloning and sequencing analysis revealed that the embryonic truncated MK, in which the conserved domain is in-frame deleted, presumably producing a novel secreted small peptide, is different from the truncated form in human cancer tissues, whose deletion results in a frame-shift mutation. Our data suggest that MK may play a role in epithelium-mesenchyme interactions, blood vessel signaling, and the decision of proliferation vs differentiation. Detection of the transiently expressed truncated MK reveals its novel function in development and sheds light on its role in carcinogenesis

  17. Modifications of Geometric Truncation of the Scattering Phase Function

    Science.gov (United States)

    Radkevich, A.

    2017-12-01

    Phase function (PF) of light scattering on large atmospheric particles has very strong peak in forward direction constituting a challenge for accurate numerical calculations of radiance. Such accurate (and fast) evaluations are important in the problems of remote sensing of the atmosphere. Scaling transformation replaces original PF with a sum of the delta function and a new regular smooth PF. A number of methods to construct such a PF were suggested. Delta-M and delta-fit methods require evaluation of the PF moments which imposes a numerical problem if strongly anisotropic PF is given as a function of angle. Geometric truncation keeps the original PF unchanged outside the forward peak cone replacing it with a constant within the cone. This approach is designed to preserve the asymmetry parameter. It has two disadvantages: 1) PF has discontinuity at the cone; 2) the choice of the cone is subjective, no recommendations were provided on the choice of the truncation angle. This choice affects both truncation fraction and the value of the phase function within the forward cone. Both issues are addressed in this study. A simple functional form of the replacement PF is suggested. This functional form allows for a number of modifications. This study consider 3 versions providing continuous PF. The considered modifications also bear either of three properties: preserve asymmetry parameter, provide continuity of the 1st derivative of the PF, and preserve mean scattering angle. The second problem mentioned above is addressed with a heuristic approach providing unambiguous criterion of selection of the truncation angle. The approach showed good performance on liquid water and ice clouds with different particle size distributions. Suggested modifications were tested on different cloud PFs using both discrete ordinates and Monte Carlo methods. It was showed that the modifications provide better accuracy of the radiance computation compare to the original geometric truncation.

  18. A Support Vector Machine Approach for Truncated Fingerprint Image Detection from Sweeping Fingerprint Sensors

    Science.gov (United States)

    Chen, Chi-Jim; Pai, Tun-Wen; Cheng, Mox

    2015-01-01

    A sweeping fingerprint sensor converts fingerprints on a row by row basis through image reconstruction techniques. However, a built fingerprint image might appear to be truncated and distorted when the finger was swept across a fingerprint sensor at a non-linear speed. If the truncated fingerprint images were enrolled as reference targets and collected by any automated fingerprint identification system (AFIS), successful prediction rates for fingerprint matching applications would be decreased significantly. In this paper, a novel and effective methodology with low time computational complexity was developed for detecting truncated fingerprints in a real time manner. Several filtering rules were implemented to validate existences of truncated fingerprints. In addition, a machine learning method of supported vector machine (SVM), based on the principle of structural risk minimization, was applied to reject pseudo truncated fingerprints containing similar characteristics of truncated ones. The experimental result has shown that an accuracy rate of 90.7% was achieved by successfully identifying truncated fingerprint images from testing images before AFIS enrollment procedures. The proposed effective and efficient methodology can be extensively applied to all existing fingerprint matching systems as a preliminary quality control prior to construction of fingerprint templates. PMID:25835186

  19. A Support Vector Machine Approach for Truncated Fingerprint Image Detection from Sweeping Fingerprint Sensors

    Directory of Open Access Journals (Sweden)

    Chi-Jim Chen

    2015-03-01

    Full Text Available A sweeping fingerprint sensor converts fingerprints on a row by row basis through image reconstruction techniques. However, a built fingerprint image might appear to be truncated and distorted when the finger was swept across a fingerprint sensor at a non-linear speed. If the truncated fingerprint images were enrolled as reference targets and collected by any automated fingerprint identification system (AFIS, successful prediction rates for fingerprint matching applications would be decreased significantly. In this paper, a novel and effective methodology with low time computational complexity was developed for detecting truncated fingerprints in a real time manner. Several filtering rules were implemented to validate existences of truncated fingerprints. In addition, a machine learning method of supported vector machine (SVM, based on the principle of structural risk minimization, was applied to reject pseudo truncated fingerprints containing similar characteristics of truncated ones. The experimental result has shown that an accuracy rate of 90.7% was achieved by successfully identifying truncated fingerprint images from testing images before AFIS enrollment procedures. The proposed effective and efficient methodology can be extensively applied to all existing fingerprint matching systems as a preliminary quality control prior to construction of fingerprint templates.

  20. Propagation of truncated modified Laguerre-Gaussian beams

    Science.gov (United States)

    Deng, D.; Li, J.; Guo, Q.

    2010-01-01

    By expanding the circ function into a finite sum of complex Gaussian functions and applying the Collins formula, the propagation of hard-edge diffracted modified Laguerre-Gaussian beams (MLGBs) through a paraxial ABCD system is studied, and the approximate closed-form propagation expression of hard-edge diffracted MLGBs is obtained. The transverse intensity distribution of the MLGB carrying finite power can be characterized by a single bright and symmetric ring during propagation when the aperture radius is very large. Starting from the definition of the generalized truncated second-order moments, the beam quality factor of MLGBs through a hard-edged circular aperture is investigated in a cylindrical coordinate system, which turns out to be dependent on the truncated radius and the beam orders.

  1. Balanced truncation for linear switched systems

    DEFF Research Database (Denmark)

    Petreczky, Mihaly; Wisniewski, Rafal; Leth, John-Josef

    2013-01-01

    In this paper, we present a theoretical analysis of the model reduction algorithm for linear switched systems from Shaker and Wisniewski (2011, 2009) and . This algorithm is a reminiscence of the balanced truncation method for linear parameter varying systems (Wood et al., 1996) [3]. Specifically...

  2. Truncated Newton-Raphson Methods for Quasicontinuum Simulations

    National Research Council Canada - National Science Library

    Liang, Yu; Kanapady, Ramdev; Chung, Peter W

    2006-01-01

    .... In this research, we report the effectiveness of the truncated Newton-Raphson method and quasi-Newton method with low-rank Hessian update strategy that are evaluated against the full Newton-Raphson...

  3. The Stars and Gas in Outer Parts of Galaxy Disks : Extended or Truncated, Flat or Warped?

    NARCIS (Netherlands)

    van der Kruit, P. C.; Funes, JG; Corsini, EM

    2008-01-01

    I review observations of truncations of stellar disks and models for their origin, compare observations of truncations in moderately inclined galaxies to those in edge-on systems and discuss the relation between truncations and H I-warps and their systematics and origin. Truncations are a common

  4. On truncated Taylor series and the position of their spurious zeros

    DEFF Research Database (Denmark)

    Christiansen, Søren; Madsen, Per A.

    2006-01-01

    A truncated Taylor series, or a Taylor polynomial, which may appear when treating the motion of gravity water waves, is obtained by truncating an infinite Taylor series for a complex, analytical function. For such a polynomial the position of the complex zeros is considered in case the Taylor...

  5. Closed-form kinetic parameter estimation solution to the truncated data problem

    International Nuclear Information System (INIS)

    Zeng, Gengsheng L; Kadrmas, Dan J; Gullberg, Grant T

    2010-01-01

    In a dedicated cardiac single photon emission computed tomography (SPECT) system, the detectors are focused on the heart and the background is truncated in the projections. Reconstruction using truncated data results in biased images, leading to inaccurate kinetic parameter estimates. This paper has developed a closed-form kinetic parameter estimation solution to the dynamic emission imaging problem. This solution is insensitive to the bias in the reconstructed images that is caused by the projection data truncation. This paper introduces two new ideas: (1) it includes background bias as an additional parameter to estimate, and (2) it presents a closed-form solution for compartment models. The method is based on the following two assumptions: (i) the amount of the bias is directly proportional to the truncated activities in the projection data, and (ii) the background concentration is directly proportional to the concentration in the myocardium. In other words, the method assumes that the image slice contains only the heart and the background, without other organs, that the heart is not truncated, and that the background radioactivity is directly proportional to the radioactivity in the blood pool. As long as the background activity can be modeled, the proposed method is applicable regardless of the number of compartments in the model. For simplicity, the proposed method is presented and verified using a single compartment model with computer simulations using both noiseless and noisy projections.

  6. Analytic reconstruction algorithms for triple-source CT with horizontal data truncation

    International Nuclear Information System (INIS)

    Chen, Ming; Yu, Hengyong

    2015-01-01

    Purpose: This paper explores a triple-source imaging method with horizontal data truncation to enlarge the field of view (FOV) for big objects. Methods: The study is conducted by using theoretical analysis, mathematical deduction, and numerical simulations. The proposed algorithms are implemented in c + + and MATLAB. While the basic platform is constructed in MATLAB, the computationally intensive segments are coded in c + +, which are linked via a MEX interface. Results: A triple-source circular scanning configuration with horizontal data truncation is developed, where three pairs of x-ray sources and detectors are unevenly distributed on the same circle to cover the whole imaging object. For this triple-source configuration, a fan-beam filtered backprojection-type algorithm is derived for truncated full-scan projections without data rebinning. The algorithm is also extended for horizontally truncated half-scan projections and cone-beam projections in a Feldkamp-type framework. Using their method, the FOV is enlarged twofold to threefold to scan bigger objects with high speed and quality. The numerical simulation results confirm the correctness and effectiveness of the developed algorithms. Conclusions: The triple-source scanning configuration with horizontal data truncation cannot only keep most of the advantages of a traditional multisource system but also cover a larger FOV for big imaging objects. In addition, because the filtering is shift-invariant, the proposed algorithms are very fast and easily parallelized on graphic processing units

  7. SSTAR, a Stand-Alone Easy-To-Use Antimicrobial Resistance Gene Predictor.

    Science.gov (United States)

    de Man, Tom J B; Limbago, Brandi M

    2016-01-01

    We present the easy-to-use Sequence Search Tool for Antimicrobial Resistance, SSTAR. It combines a locally executed BLASTN search against a customizable database with an intuitive graphical user interface for identifying antimicrobial resistance (AR) genes from genomic data. Although the database is initially populated from a public repository of acquired resistance determinants (i.e., ARG-ANNOT), it can be customized for particular pathogen groups and resistance mechanisms. For instance, outer membrane porin sequences associated with carbapenem resistance phenotypes can be added, and known intrinsic mechanisms can be included. Unique about this tool is the ability to easily detect putative new alleles and truncated versions of existing AR genes. Variants and potential new alleles are brought to the attention of the user for further investigation. For instance, SSTAR is able to identify modified or truncated versions of porins, which may be of great importance in carbapenemase-negative carbapenem-resistant Enterobacteriaceae. SSTAR is written in Java and is therefore platform independent and compatible with both Windows and Unix operating systems. SSTAR and its manual, which includes a simple installation guide, are freely available from https://github.com/tomdeman-bio/Sequence-Search-Tool-for-Antimicrobial-Resistance-SSTAR-. IMPORTANCE Whole-genome sequencing (WGS) is quickly becoming a routine method for identifying genes associated with antimicrobial resistance (AR). However, for many microbiologists, the use and analysis of WGS data present a substantial challenge. We developed SSTAR, software with a graphical user interface that enables the identification of known AR genes from WGS and has the unique capacity to easily detect new variants of known AR genes, including truncated protein variants. Current software solutions do not notify the user when genes are truncated and, therefore, likely nonfunctional, which makes phenotype predictions less accurate. SSTAR

  8. A Line Search Multilevel Truncated Newton Algorithm for Computing the Optical Flow

    Directory of Open Access Journals (Sweden)

    Lluís Garrido

    2015-06-01

    Full Text Available We describe the implementation details and give the experimental results of three optimization algorithms for dense optical flow computation. In particular, using a line search strategy, we evaluate the performance of the unilevel truncated Newton method (LSTN, a multiresolution truncated Newton (MR/LSTN and a full multigrid truncated Newton (FMG/LSTN. We use three image sequences and four models of optical flow for performance evaluation. The FMG/LSTN algorithm is shown to lead to better optical flow estimation with less computational work than both the LSTN and MR/LSTN algorithms.

  9. Low-mode truncation methods in the sine-Gordon equation

    International Nuclear Information System (INIS)

    Xiong Chuyu.

    1991-01-01

    In this dissertation, the author studies the chaotic and coherent motions (i.e., low-dimensional chaotic attractor) in some near integrable partial differential equations, particularly the sine-Gordon equation and the nonlinear Schroedinger equation. In order to study the motions, he uses low mode truncation methods to reduce these partial differential equations to some truncated models (low-dimensional ordinary differential equations). By applying many methods available to low-dimensional ordinary differential equations, he can understand the low-dimensional chaotic attractor of PDE's much better. However, there are two important questions one needs to answer: (1) How many modes is good enough for the low mode truncated models to capture the dynamics uniformly? (2) Is the chaotic attractor in a low mode truncated model close to the chaotic attractor in the original PDE? And how close is? He has developed two groups of powerful methods to help to answer these two questions. They are the computation methods of continuation and local bifurcation, and local Lyapunov exponents and Lyapunov exponents. Using these methods, he concludes that the 2N-nls ODE is a good model for the sine-Gordon equation and the nonlinear Schroedinger equation provided one chooses a 'good' basis and uses 'enough' modes (where 'enough' depends on the parameters of the system but is small for the parameter studied here). Therefore, one can use 2N-nls ODE to study the chaos of PDE's in more depth

  10. The use of hygromycin phosphotransferase gene (hpt) with an ...

    African Journals Online (AJOL)

    Previously, we have developed a marker-off system to truncate a selec marker in transgenic plants by locating one end of the transposon in the intron of the marker gene (glyphosate-tolerant epsps gene). In order to expand this technique to those marker genes without intron in this report, we created an artificial intron ...

  11. Molecular evidence for historical presence of knock-down resistance in Anopheles albimanus, a key malaria vector in Latin America.

    Science.gov (United States)

    Lol, Juan C; Castellanos, María E; Liebman, Kelly A; Lenhart, Audrey; Pennington, Pamela M; Padilla, Norma R

    2013-09-18

    Anopheles albimanus is a key malaria vector in the northern neotropics. Current vector control measures in the region are based on mass distributions of long-lasting insecticidal nets (LLINs) and focal indoor residual spraying (IRS) with pyrethroids. Resistance to pyrethroid insecticides can be mediated by increased esterase and/or multi-function oxidase activity and/or mutations in the voltage-gated sodium channel gene. The aim of this work was to characterize the homologous kdr region of the voltage-gated sodium channel gene in An. albimanus and to conduct a preliminary retrospective analysis of field samples collected in the 1990's, coinciding with a time of intense pyrethroid application related to agricultural and public health insect control in the region. Degenerate primers were designed to amplify the homologous kdr region in a pyrethroid-susceptible laboratory strain (Sanarate) of An. albimanus. Subsequently, a more specific primer pair was used to amplify and sequence the region that contains the 1014 codon associated with pyrethroid resistance in other Anopheles spp. (L1014F, L1014S or L1014C). Direct sequencing of the PCR products confirmed the presence of the susceptible kdr allele in the Sanarate strain (L1014) and the presence of homozygous-resistant kdr alleles in field-collected individuals from Mexico (L1014F), Nicaragua (L1014C) and Costa Rica (L1014C). For the first time, the kdr region in An. albimanus is described. Furthermore, molecular evidence suggests the presence of kdr-type resistance in field-collected An. albimanus in Mesoamerica in the 1990s. Further research is needed to conclusively determine an association between the genotypes and resistant phenotypes, and to what extent they may compromise current vector control efforts.

  12. N-terminally truncated POM121C inhibits HIV-1 replication.

    Directory of Open Access Journals (Sweden)

    Hideki Saito

    Full Text Available Recent studies have identified host cell factors that regulate early stages of HIV-1 infection including viral cDNA synthesis and orientation of the HIV-1 capsid (CA core toward the nuclear envelope, but it remains unclear how viral DNA is imported through the nuclear pore and guided to the host chromosomal DNA. Here, we demonstrate that N-terminally truncated POM121C, a component of the nuclear pore complex, blocks HIV-1 infection. This truncated protein is predominantly localized in the cytoplasm, does not bind to CA, does not affect viral cDNA synthesis, reduces the formation of 2-LTR and diminished the amount of integrated proviral DNA. Studies with an HIV-1-murine leukemia virus (MLV chimeric virus carrying the MLV-derived Gag revealed that Gag is a determinant of this inhibition. Intriguingly, mutational studies have revealed that the blockade by N-terminally-truncated POM121C is closely linked to its binding to importin-β/karyopherin subunit beta 1 (KPNB1. These results indicate that N-terminally-truncated POM121C inhibits HIV-1 infection after completion of reverse transcription and before integration, and suggest an important role for KPNB1 in HIV-1 replication.

  13. Estimation of Panel Data Regression Models with Two-Sided Censoring or Truncation

    DEFF Research Database (Denmark)

    Alan, Sule; Honore, Bo E.; Hu, Luojia

    2014-01-01

    This paper constructs estimators for panel data regression models with individual speci…fic heterogeneity and two–sided censoring and truncation. Following Powell (1986) the estimation strategy is based on moment conditions constructed from re–censored or re–truncated residuals. While these moment...

  14. Overexpression of the truncated version of ILV2 enhances glycerol production in Saccharomyces cerevisiae.

    Science.gov (United States)

    Murashchenko, Lidiia; Abbas, Charles; Dmytruk, Kostyantyn; Sibirny, Andriy

    2016-08-01

    Acetolactate synthase is a mitochondrial enzyme that catalyses the conversion of two pyruvate molecules to an acetolactate molecule with release of carbon dioxide. The overexpression of the truncated version of the corresponding gene, ILV2, that codes for presumably cytosolic acetolactate synthase in the yeast Saccharomyces cerevisiae, led to a decrease in intracellular pyruvate concentration. This recombinant strain was also characterized by a four-fold increase in glycerol production, with a concomitant 1.8-fold reduction in ethanol production, when compared to that of the wild-type strain under anaerobic conditions in a glucose alcoholic fermentation. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  15. A generalized right truncated bivariate Poisson regression model with applications to health data.

    Science.gov (United States)

    Islam, M Ataharul; Chowdhury, Rafiqul I

    2017-01-01

    A generalized right truncated bivariate Poisson regression model is proposed in this paper. Estimation and tests for goodness of fit and over or under dispersion are illustrated for both untruncated and right truncated bivariate Poisson regression models using marginal-conditional approach. Estimation and test procedures are illustrated for bivariate Poisson regression models with applications to Health and Retirement Study data on number of health conditions and the number of health care services utilized. The proposed test statistics are easy to compute and it is evident from the results that the models fit the data very well. A comparison between the right truncated and untruncated bivariate Poisson regression models using the test for nonnested models clearly shows that the truncated model performs significantly better than the untruncated model.

  16. Bounded real and positive real balanced truncation using Σ-normalised coprime factors

    NARCIS (Netherlands)

    Trentelman, H.L.

    2009-01-01

    In this article, we will extend the method of balanced truncation using normalised right coprime factors of the system transfer matrix to balanced truncation with preservation of half line dissipativity. Special cases are preservation of positive realness and bounded realness. We consider a half

  17. No chiral truncation of quantum log gravity?

    Science.gov (United States)

    Andrade, Tomás; Marolf, Donald

    2010-03-01

    At the classical level, chiral gravity may be constructed as a consistent truncation of a larger theory called log gravity by requiring that left-moving charges vanish. In turn, log gravity is the limit of topologically massive gravity (TMG) at a special value of the coupling (the chiral point). We study the situation at the level of linearized quantum fields, focussing on a unitary quantization. While the TMG Hilbert space is continuous at the chiral point, the left-moving Virasoro generators become ill-defined and cannot be used to define a chiral truncation. In a sense, the left-moving asymptotic symmetries are spontaneously broken at the chiral point. In contrast, in a non-unitary quantization of TMG, both the Hilbert space and charges are continuous at the chiral point and define a unitary theory of chiral gravity at the linearized level.

  18. Reduction of variable-truncation artifacts from beam occlusion during in situ x-ray tomography

    Science.gov (United States)

    Borg, Leise; Jørgensen, Jakob S.; Frikel, Jürgen; Sporring, Jon

    2017-12-01

    Many in situ x-ray tomography studies require experimental rigs which may partially occlude the beam and cause parts of the projection data to be missing. In a study of fluid flow in porous chalk using a percolation cell with four metal bars drastic streak artifacts arise in the filtered backprojection (FBP) reconstruction at certain orientations. Projections with non-trivial variable truncation caused by the metal bars are the source of these variable-truncation artifacts. To understand the artifacts a mathematical model of variable-truncation data as a function of metal bar radius and distance to sample is derived and verified numerically and with experimental data. The model accurately describes the arising variable-truncation artifacts across simulated variations of the experimental setup. Three variable-truncation artifact-reduction methods are proposed, all aimed at addressing sinogram discontinuities that are shown to be the source of the streaks. The ‘reduction to limited angle’ (RLA) method simply keeps only non-truncated projections; the ‘detector-directed smoothing’ (DDS) method smooths the discontinuities; while the ‘reflexive boundary condition’ (RBC) method enforces a zero derivative at the discontinuities. Experimental results using both simulated and real data show that the proposed methods effectively reduce variable-truncation artifacts. The RBC method is found to provide the best artifact reduction and preservation of image features using both visual and quantitative assessment. The analysis and artifact-reduction methods are designed in context of FBP reconstruction motivated by computational efficiency practical for large, real synchrotron data. While a specific variable-truncation case is considered, the proposed methods can be applied to general data cut-offs arising in different in situ x-ray tomography experiments.

  19. Modulation of gene expression made easy

    DEFF Research Database (Denmark)

    Solem, Christian; Jensen, Peter Ruhdal

    2002-01-01

    A new approach for modulating gene expression, based on randomization of promoter (spacer) sequences, was developed. The method was applied to chromosomal genes in Lactococcus lactis and shown to generate libraries of clones with broad ranges of expression levels of target genes. In one example...... that the method can be applied to modulating the expression of native genes on the chromosome. We constructed a series of strains in which the expression of the las operon, containing the genes pfk, pyk, and ldh, was modulated by integrating a truncated copy of the pfk gene. Importantly, the modulation affected...

  20. Amplitude reconstruction from complete photoproduction experiments and truncated partial-wave expansions

    International Nuclear Information System (INIS)

    Workman, R. L.; Tiator, L.; Wunderlich, Y.; Doring, M.; Haberzettl, H.

    2017-01-01

    Here, we compare the methods of amplitude reconstruction, for a complete experiment and a truncated partial-wave analysis, applied to the photoproduction of pseudoscalar mesons. The approach is pedagogical, showing in detail how the amplitude reconstruction (observables measured at a single energy and angle) is related to a truncated partial-wave analysis (observables measured at a single energy and a number of angles).

  1. Modified Truncated Multiplicity Analysis to Improve Verification of Uranium Fuel Cycle Materials

    International Nuclear Information System (INIS)

    LaFleur, A.; Miller, K.; Swinhoe, M.; Belian, A.; Croft, S.

    2015-01-01

    Accurate verification of 235U enrichment and mass in UF6 storage cylinders and the UO2F2 holdup contained in the process equipment is needed to improve international safeguards and nuclear material accountancy at uranium enrichment plants. Small UF6 cylinders (1.5'' and 5'' diameter) are used to store the full range of enrichments from depleted to highly-enriched UF6. For independent verification of these materials, it is essential that the 235U mass and enrichment measurements do not rely on facility operator declarations. Furthermore, in order to be deployed by IAEA inspectors to detect undeclared activities (e.g., during complementary access), it is also imperative that the measurement technique is quick, portable, and sensitive to a broad range of 235U masses. Truncated multiplicity analysis is a technique that reduces the variance in the measured count rates by only considering moments 1, 2, and 3 of the multiplicity distribution. This is especially important for reducing the uncertainty in the measured doubles and triples rates in environments with a high cosmic ray background relative to the uranium signal strength. However, we believe that the existing truncated multiplicity analysis throws away too much useful data by truncating the distribution after the third moment. This paper describes a modified truncated multiplicity analysis method that determines the optimal moment to truncate the multiplicity distribution based on the measured data. Experimental measurements of small UF6 cylinders and UO2F2 working reference materials were performed at Los Alamos National Laboratory (LANL). The data were analyzed using traditional and modified truncated multiplicity analysis to determine the optimal moment to truncate the multiplicity distribution to minimize the uncertainty in the measured count rates. The results from this analysis directly support nuclear safeguards at enrichment plants and provide a more accurate verification method for UF6

  2. Modeling the Effect of APC Truncation on Destruction Complex Function in Colorectal Cancer Cells

    Science.gov (United States)

    Barua, Dipak; Hlavacek, William S.

    2013-01-01

    In colorectal cancer cells, APC, a tumor suppressor protein, is commonly expressed in truncated form. Truncation of APC is believed to disrupt degradation of β—catenin, which is regulated by a multiprotein complex called the destruction complex. The destruction complex comprises APC, Axin, β—catenin, serine/threonine kinases, and other proteins. The kinases and , which are recruited by Axin, mediate phosphorylation of β—catenin, which initiates its ubiquitination and proteosomal degradation. The mechanism of regulation of β—catenin degradation by the destruction complex and the role of truncation of APC in colorectal cancer are not entirely understood. Through formulation and analysis of a rule-based computational model, we investigated the regulation of β—catenin phosphorylation and degradation by APC and the effect of APC truncation on function of the destruction complex. The model integrates available mechanistic knowledge about site-specific interactions and phosphorylation of destruction complex components and is consistent with an array of published data. We find that the phosphorylated truncated form of APC can outcompete Axin for binding to β—catenin, provided that Axin is limiting, and thereby sequester β—catenin away from Axin and the Axin-recruited kinases and . Full-length APC also competes with Axin for binding to β—catenin; however, full-length APC is able, through its SAMP repeats, which bind Axin and which are missing in truncated oncogenic forms of APC, to bring β—catenin into indirect association with Axin and Axin-recruited kinases. Because our model indicates that the positive effects of truncated APC on β—catenin levels depend on phosphorylation of APC, at the first 20-amino acid repeat, and because phosphorylation of this site is mediated by , we suggest that is a potential target for therapeutic intervention in colorectal cancer. Specific inhibition of is predicted to limit binding of β—catenin to truncated

  3. ThPOD3, a truncated polypeptide from Tamarix hispida, conferred drought tolerance in Escherichia coli.

    Science.gov (United States)

    Guo, Xiao-Hong; Jiang, Jing; Wang, Bai-Chen; Li, Hui-Yu; Wang, Yu-Cheng; Yang, Chuan-Ping; Liu, Gui-Feng

    2010-03-01

    The ThPOD1 gene encodes a peroxidase and was isolated from a Tamarix hispida NaCl-stress root cDNA library. We found that ThPOD1 expression could be induced by abiotic stresses such as cold, salt, drought and exogenous abscisic acid. These findings suggested that ThPOD1 might be involved in the plant response to environmental stresses and ABA treatment. To elucidate the function of this gene, recombinant plasmids expressing full-length ThPOD1 as well as ThPOD2 (aa 41-337), and ThPOD3 (aa 73-337) truncated polypeptides were constructed. SDS-PAGE and Western blot analyses of the fusion proteins revealed that the molecular weights of ThPOD1, ThPOD2 and ThPOD3 were approximately 57, approximately 50 and approximately 47 kDa, respectively. Stress assays of E. coli treated with the recombinant plasmids indicated that ThPOD3 could improve resistance to drought stress. This finding could potentially be used to improve plant tolerance to drought stress via gene transfer.

  4. A Lynden-Bell integral estimator for the tail index of right-truncated ...

    African Journals Online (AJOL)

    By means of a Lynden-Bell integral with deterministic threshold, Worms and Worms [A Lynden-Bell integral estimator for extremes of randomly truncated data. Statist. Probab. Lett. 2016; 109: 106-117] recently introduced an asymptotically normal estimator of the tail index for randomly right-truncated Pareto-type data.

  5. Truncated States Obtained by Iteration

    International Nuclear Information System (INIS)

    Cardoso, W. B.; Almeida, N. G. de

    2008-01-01

    We introduce the concept of truncated states obtained via iterative processes (TSI) and study its statistical features, making an analogy with dynamical systems theory (DST). As a specific example, we have studied TSI for the doubling and the logistic functions, which are standard functions in studying chaos. TSI for both the doubling and logistic functions exhibit certain similar patterns when their statistical features are compared from the point of view of DST

  6. Gene-based testing of interactions in association studies of quantitative traits.

    Directory of Open Access Journals (Sweden)

    Li Ma

    Full Text Available Various methods have been developed for identifying gene-gene interactions in genome-wide association studies (GWAS. However, most methods focus on individual markers as the testing unit, and the large number of such tests drastically erodes statistical power. In this study, we propose novel interaction tests of quantitative traits that are gene-based and that confer advantage in both statistical power and biological interpretation. The framework of gene-based gene-gene interaction (GGG tests combine marker-based interaction tests between all pairs of markers in two genes to produce a gene-level test for interaction between the two. The tests are based on an analytical formula we derive for the correlation between marker-based interaction tests due to linkage disequilibrium. We propose four GGG tests that extend the following P value combining methods: minimum P value, extended Simes procedure, truncated tail strength, and truncated P value product. Extensive simulations point to correct type I error rates of all tests and show that the two truncated tests are more powerful than the other tests in cases of markers involved in the underlying interaction not being directly genotyped and in cases of multiple underlying interactions. We applied our tests to pairs of genes that exhibit a protein-protein interaction to test for gene-level interactions underlying lipid levels using genotype data from the Atherosclerosis Risk in Communities study. We identified five novel interactions that are not evident from marker-based interaction testing and successfully replicated one of these interactions, between SMAD3 and NEDD9, in an independent sample from the Multi-Ethnic Study of Atherosclerosis. We conclude that our GGG tests show improved power to identify gene-level interactions in existing, as well as emerging, association studies.

  7. The Dynamics of Truncated Black Hole Accretion Disks. I. Viscous Hydrodynamic Case

    Energy Technology Data Exchange (ETDEWEB)

    Hogg, J. Drew; Reynolds, Christopher S. [Department of Astronomy, University of Maryland, College Park, MD 20742 (United States)

    2017-07-10

    Truncated accretion disks are commonly invoked to explain the spectro-temporal variability in accreting black holes in both small systems, i.e., state transitions in galactic black hole binaries (GBHBs), and large systems, i.e., low-luminosity active galactic nuclei (LLAGNs). In the canonical truncated disk model of moderately low accretion rate systems, gas in the inner region of the accretion disk occupies a hot, radiatively inefficient phase, which leads to a geometrically thick disk, while the gas in the outer region occupies a cooler, radiatively efficient phase that resides in the standard geometrically thin disk. Observationally, there is strong empirical evidence to support this phenomenological model, but a detailed understanding of the dynamics of truncated disks is lacking. We present a well-resolved viscous, hydrodynamic simulation that uses an ad hoc cooling prescription to drive a thermal instability and, hence, produce the first sustained truncated accretion disk. With this simulation, we perform a study of the dynamics, angular momentum transport, and energetics of a truncated disk. We find that the time variability introduced by the quasi-periodic transition of gas from efficient cooling to inefficient cooling impacts the evolution of the simulated disk. A consequence of the thermal instability is that an outflow is launched from the hot/cold gas interface, which drives large, sub-Keplerian convective cells into the disk atmosphere. The convective cells introduce a viscous θ − ϕ stress that is less than the generic r − ϕ viscous stress component, but greatly influences the evolution of the disk. In the truncated disk, we find that the bulk of the accreted gas is in the hot phase.

  8. A Multistep Extending Truncation Method towards Model Construction of Infinite-State Markov Chains

    Directory of Open Access Journals (Sweden)

    Kemin Wang

    2014-01-01

    Full Text Available The model checking of Infinite-State Continuous Time Markov Chains will inevitably encounter the state explosion problem when constructing the CTMCs model; our method is to get a truncated model of the infinite one; to get a sufficient truncated model to meet the model checking of Continuous Stochastic Logic based system properties, we propose a multistep extending advanced truncation method towards model construction of CTMCs and implement it in the INFAMY model checker; the experiment results show that our method is effective.

  9. Family Therapy for the "Truncated" Nuclear Family.

    Science.gov (United States)

    Zuk, Gerald H.

    1980-01-01

    The truncated nuclear family consists of a two-generation group in which conflict has produced a polarization of values. The single-parent family is at special risk. Go-between process enables the therapist to depolarize sharply conflicted values and reduce pathogenic relating. (Author)

  10. Molecular dynamics simulations of lipid bilayers : major artifacts due to truncating electrostatic interactions

    NARCIS (Netherlands)

    Patra, M.; Karttunen, M.E.J.; Hyvönen, M.T.; Falck, E.; Lindqvist, P.; Vattulainen, I.

    2003-01-01

    We study the influence of truncating the electrostatic interactions in a fully hydrated pure dipalmitoylphosphatidylcholine (DPPC) bilayer through 20 ns molecular dynamics simulations. The computations in which the electrostatic interactions were truncated are compared to similar simulations using

  11. On the viability of the truncated Israel–Stewart theory in cosmology

    International Nuclear Information System (INIS)

    Shogin, Dmitry; Amundsen, Per Amund; Hervik, Sigbjørn

    2015-01-01

    We apply the causal Israel–Stewart theory of irreversible thermodynamics to model the matter content of the Universe as a dissipative fluid with bulk and shear viscosity. Along with the full transport equations we consider their widely used truncated version. By implementing a dynamical systems approach to Bianchi type IV and V cosmological models with and without cosmological constant, we determine the future asymptotic states of such Universes and show that the truncated Israel–Stewart theory leads to solutions essentially different from the full theory. The solutions of the truncated theory may also manifest unphysical properties. Finally, we find that in the full theory shear viscosity can give a substantial rise to dissipative fluxes, driving the fluid extremely far from equilibrium, where the linear Israel–Stewart theory ceases to be valid. (paper)

  12. Riesz Representation Theorem on Bilinear Spaces of Truncated Laurent Series

    Directory of Open Access Journals (Sweden)

    Sabarinsyah

    2017-06-01

    Full Text Available In this study a generalization of the Riesz representation theorem on non-degenerate bilinear spaces, particularly on spaces of truncated Laurent series, was developed. It was shown that any linear functional on a non-degenerate bilinear space is representable by a unique element of the space if and only if its kernel is closed. Moreover an explicit equivalent condition can be identified for the closedness property of the kernel when the bilinear space is a space of truncated Laurent series.

  13. CRISPR/Cas9-induced transgene insertion and telomere-associated truncation of a single human chromosome for chromosome engineering in CHO and A9 cells.

    Science.gov (United States)

    Uno, Narumi; Hiramatsu, Kei; Uno, Katsuhiro; Komoto, Shinya; Kazuki, Yasuhiro; Oshimura, Mitsuo

    2017-10-06

    Chromosome engineering techniques including gene insertion, telomere-associated truncation and microcell-mediated chromosome transfer (MMCT) are powerful tools for generation of humanised model animal, containing megabase-sized genomic fragments. However, these techniques require two cell lines: homologous recombination (HR)-proficient DT40 cells for chromosome modification, and CHO cells for transfer to recipient cells. Here we show an improved technique using a combination of CRISPR/Cas9-induced HR in CHO and mouse A9 cells without DT40 cells following MMCT to recipient cells. Transgene insertion was performed in CHO cells with the insertion of enhanced green fluorescence protein (EGFP) using CRISPR/Cas9 and a circular targeting vector containing two 3 kb HR arms. Telomere-associated truncation was performed in CHO cells using CRISPR/Cas9 and a linearised truncation vector containing a single 7 kb HR arm at the 5' end, a 1 kb artificial telomere at the 3' end. At least 11% and 6% of the targeting efficiency were achieved for transgene insertion and telomere-associated truncation, respectively. The transgene insertion was also confirmed in A9 cells (29%). The modified chromosomes were transferrable to other cells. Thus, this CHO and A9 cell-mediated chromosome engineering using the CRISPR/Cas9 for direct transfer of the modified chromosome is a rapid technique that will facilitate chromosome manipulation.

  14. Pressure-sensitive paint on a truncated cone in hypersonic flow at incidences

    International Nuclear Information System (INIS)

    Yang, L.; Erdem, E.; Zare-Behtash, H.; Kontis, K.; Saravanan, S.

    2012-01-01

    Highlights: ► Global pressure map over the truncated cone is obtained at various incidence angles in Mach 5 flow. ► Successful application of AA-PSP in hypersonic flow expands operation area of this technique. ► AA-PSP reveals complex three-dimensional pattern which is difficult for transducer to obtain. ► Quantitative data provides strong correlation with colour Schlieren and oil flow results. ► High spatial resolution pressure mappings identify small scale vortices and flow separation. - Abstract: The flow over a truncated cone is a classical and fundamental problem for aerodynamic research due to its three-dimensional and complicated characteristics. The flow is made more complex when examining high angles of incidence. Recently these types of flows have drawn more attention for the purposes of drag reduction in supersonic/hypersonic flows. In the present study the flow over a truncated cone at various incidences was experimentally investigated in a Mach 5 flow with a unit Reynolds number of 13.5 × 10 6 m −1 . The cone semi-apex angle is 15° and the truncation ratio (truncated length/cone length) is 0.5. The incidence of the model varied from −12° to 12° with 3° intervals relative to the freestream direction. The external flow around the truncated cone was visualised by colour Schlieren photography, while the surface flow pattern was revealed using the oil flow method. The surface pressure distribution was measured using the anodized aluminium pressure-sensitive paint (AA-PSP) technique. Both top and sideviews of the pressure distribution on the model surface were acquired at various incidences. AA-PSP showed high pressure sensitivity and captured the complicated flow structures which correlated well with the colour Schlieren and oil flow visualisation results.

  15. Genomic analysis of primordial dwarfism reveals novel disease genes.

    Science.gov (United States)

    Shaheen, Ranad; Faqeih, Eissa; Ansari, Shinu; Abdel-Salam, Ghada; Al-Hassnan, Zuhair N; Al-Shidi, Tarfa; Alomar, Rana; Sogaty, Sameera; Alkuraya, Fowzan S

    2014-02-01

    Primordial dwarfism (PD) is a disease in which severely impaired fetal growth persists throughout postnatal development and results in stunted adult size. The condition is highly heterogeneous clinically, but the use of certain phenotypic aspects such as head circumference and facial appearance has proven helpful in defining clinical subgroups. In this study, we present the results of clinical and genomic characterization of 16 new patients in whom a broad definition of PD was used (e.g., 3M syndrome was included). We report a novel PD syndrome with distinct facies in two unrelated patients, each with a different homozygous truncating mutation in CRIPT. Our analysis also reveals, in addition to mutations in known PD disease genes, the first instance of biallelic truncating BRCA2 mutation causing PD with normal bone marrow analysis. In addition, we have identified a novel locus for Seckel syndrome based on a consanguineous multiplex family and identified a homozygous truncating mutation in DNA2 as the likely cause. An additional novel PD disease candidate gene XRCC4 was identified by autozygome/exome analysis, and the knockout mouse phenotype is highly compatible with PD. Thus, we add a number of novel genes to the growing list of PD-linked genes, including one which we show to be linked to a novel PD syndrome with a distinct facial appearance. PD is extremely heterogeneous genetically and clinically, and genomic tools are often required to reach a molecular diagnosis.

  16. Polymorphism in leptin receptor gene was associated with obesity in ...

    African Journals Online (AJOL)

    The mutation in leptin receptor (LEPR) gene causes splicing abnormality that resulted in truncated receptor, aberrant signal transduction, leptin resistance, and obesity. This study aims to determine the association of LEPR gene polymorphisms, rs1137100 and rs1137101, on phenotype and leptin level between obese and ...

  17. Regulation of the intronic promoter of rat estrogen receptor alpha gene, responsible for truncated estrogen receptor product-1 expression.

    Science.gov (United States)

    Schausi, Diane; Tiffoche, Christophe; Thieulant, Marie-Lise

    2003-07-01

    We have characterized the intronic promoter of the rat estrogen receptor (ER) alpha gene, responsible for the lactotrope-specific truncated ER product (TERP)-1 isoform expression. Transcriptional regulation was investigated by transient transfections using 5'-deletion constructs. TERP promoter constructs were highly active in MMQ cells, a pure lactotrope cell line, whereas a low basal activity was detected in alphaT3-1 gonadotrope cells or in COS-7 monkey kidney cells. Serial deletion analysis revealed that 1) a minimal -693-bp region encompassing the TATA box is sufficient to allow lactotrope-specific expression; 2) the promoter contains strong positive cis-acting elements both in the distal and proximal regions, and 3) the region spanning the -1698/-1194 region includes repressor elements. Transient transfection studies, EMSAs, and gel shifts demonstrated that estrogen activates the TERP promoter via an estrogen-responsive element (ERE1) located within the proximal region. Mutation of ERE1 site completely abolishes the estradiol-dependent transcription, indicating that ERE1 site is sufficient to confer estrogen responsiveness to TERP promoter. In addition, ERalpha action was synergized by transfection of the pituitary-specific factor Pit-1. EMSAs showed that a single Pit-1 DNA binding element in the vicinity of the TATA box is sufficient to confer response by the TERP promoter. In conclusion, we demonstrated, for the first time, that TERP promoter regulation involves ERE and Pit-1 cis-elements and corresponding trans-acting factors, which could play a role in the physiological changes that occur in TERP-1 transcription in lactotrope cells.

  18. On truncations of the exact renormalization group

    CERN Document Server

    Morris, T R

    1994-01-01

    We investigate the Exact Renormalization Group (ERG) description of (Z_2 invariant) one-component scalar field theory, in the approximation in which all momentum dependence is discarded in the effective vertices. In this context we show how one can perform a systematic search for non-perturbative continuum limits without making any assumption about the form of the lagrangian. Concentrating on the non-perturbative three dimensional Wilson fixed point, we then show that the sequence of truncations n=2,3,\\dots, obtained by expanding about the field \\varphi=0 and discarding all powers \\varphi^{2n+2} and higher, yields solutions that at first converge to the answer obtained without truncation, but then cease to further converge beyond a certain point. No completely reliable method exists to reject the many spurious solutions that are also found. These properties are explained in terms of the analytic behaviour of the untruncated solutions -- which we describe in some detail.

  19. Resonant Excitation of a Truncated Metamaterial Cylindrical Shell by a Thin Wire Monopole

    DEFF Research Database (Denmark)

    Kim, Oleksiy S.; Erentok, Aycan; Breinbjerg, Olav

    2009-01-01

    A truncated metamaterial cylindrical shell excited by a thin wire monopole is investigated using the integral equation technique as well as the finite element method. Simulations reveal a strong field singularity at the edge of the truncated cylindrical shell, which critically affects the matching...

  20. Squeezing in multi-mode nonlinear optical state truncation

    International Nuclear Information System (INIS)

    Said, R.S.; Wahiddin, M.R.B.; Umarov, B.A.

    2007-01-01

    In this Letter, we show that multi-mode qubit states produced via nonlinear optical state truncation driven by classical external pumpings exhibit squeezing condition. We restrict our discussions to the two- and three-mode cases

  1. Identification of TCT, a novel knockdown resistance allele mutation and analysis of resistance detection methods in the voltage-gated Na⁺ channel of Culex pipiens pallens from Shandong Province, China.

    Science.gov (United States)

    Liu, Hong-Mei; Cheng, Peng; Huang, Xiaodan; Dai, Yu-Hua; Wang, Hai-Fang; Liu, Li-Juan; Zhao, Yu-Qiang; Wang, Huai-Wei; Gong, Mao-Qing

    2013-02-01

    The present study aimed to investigate deltamethrin resistance in Culex pipiens pallens (C. pipiens pallens) mosquitoes and its correlation with knockdown resistance (kdr) mutations. In addition, mosquito‑resistance testing methods were analyzed. Using specific primers in polymerase chain reaction (PCR) and allele-specific (AS)-PCR, kdr gene sequences isolated from wild C. pipiens pallens mosquitoes were sequenced. Linear regression analysis was used to determine the correlation between the mutations and deltamethrin resistance. A kdr allelic gene was cloned and sequenced. Analysis of the DNA sequences revealed the presence of two point mutations at the L1014 residue in the IIS6 transmembrane segment of the voltage‑gated sodium channel (VGSC): L1014F, TTA→TTT, replacing a leucine (L) with a phenylalanine (F); L1014S, TTA→TCA, replacing leucine (L) with serine (S). Two alternative kdr-like mutations, L1014F and L1014S, were identified to be positively correlated with the deltamethrin-resistant phenotype. In addition a novel mutation, TCT, was identified in the VGSC of C. pipiens pallens. PCR and AS-PCR yielded consistent results with respect to mosquito resistance. However, the detection rate of PCR was higher than that of AS-PCR. Further studies are required to determine the specific resistance mechanism. PCR and AS-PCR demonstrated suitability for mosquito resistance field tests, however, the former method may be superior to the latter.

  2. Multiple origins of knockdown resistance mutations in the Afrotropical mosquito vector Anopheles gambiae.

    Directory of Open Access Journals (Sweden)

    João Pinto

    2007-11-01

    Full Text Available How often insecticide resistance mutations arise in natural insect populations is a fundamental question for understanding the evolution of resistance and also for modeling its spread. Moreover, the development of resistance is regarded as a favored model to study the molecular evolution of adaptive traits. In the malaria vector Anopheles gambiae two point mutations (L1014F and L1014S in the voltage-gated sodium channel gene, that confer knockdown resistance (kdr to DDT and pyrethroid insecticides, have been described. In order to determine whether resistance alleles result from single or multiple mutation events, genotyping of the kdr locus and partial sequencing of the upstream intron-1 was performed on a total of 288 A. gambiae S-form collected from 28 localities in 15 countries. Knockdown resistance alleles were found to be widespread in West Africa with co-occurrence of both 1014S and 1014F in West-Central localities. Differences in intron-1 haplotype composition suggest that kdr alleles may have arisen from at least four independent mutation events. Neutrality tests provided evidence for a selective sweep acting on this genomic region, particularly in West Africa. The frequency and distribution of these kdr haplotypes varied geographically, being influenced by an interplay between different mutational occurrences, gene flow and local selection. This has important practical implications for the management and sustainability of malaria vector control programs.

  3. truncSP: An R Package for Estimation of Semi-Parametric Truncated Linear Regression Models

    Directory of Open Access Journals (Sweden)

    Maria Karlsson

    2014-05-01

    Full Text Available Problems with truncated data occur in many areas, complicating estimation and inference. Regarding linear regression models, the ordinary least squares estimator is inconsistent and biased for these types of data and is therefore unsuitable for use. Alternative estimators, designed for the estimation of truncated regression models, have been developed. This paper presents the R package truncSP. The package contains functions for the estimation of semi-parametric truncated linear regression models using three different estimators: the symmetrically trimmed least squares, quadratic mode, and left truncated estimators, all of which have been shown to have good asymptotic and ?nite sample properties. The package also provides functions for the analysis of the estimated models. Data from the environmental sciences are used to illustrate the functions in the package.

  4. Motion of isolated open vortex filaments evolving under the truncated local induction approximation

    Science.gov (United States)

    Van Gorder, Robert A.

    2017-11-01

    The study of nonlinear waves along open vortex filaments continues to be an area of active research. While the local induction approximation (LIA) is attractive due to locality compared with the non-local Biot-Savart formulation, it has been argued that LIA appears too simple to model some relevant features of Kelvin wave dynamics, such as Kelvin wave energy transfer. Such transfer of energy is not feasible under the LIA due to integrability, so in order to obtain a non-integrable model, a truncated LIA, which breaks the integrability of the classical LIA, has been proposed as a candidate model with which to study such dynamics. Recently Laurie et al. ["Interaction of Kelvin waves and nonlocality of energy transfer in superfluids," Phys. Rev. B 81, 104526 (2010)] derived truncated LIA systematically from Biot-Savart dynamics. The focus of the present paper is to study the dynamics of a section of common open vortex filaments under the truncated LIA dynamics. We obtain the analog of helical, planar, and more general filaments which rotate without a change in form in the classical LIA, demonstrating that while quantitative differences do exist, qualitatively such solutions still exist under the truncated LIA. Conversely, solitons and breather solutions found under the LIA should not be expected under the truncated LIA, as the existence of such solutions relies on the existence of an infinite number of conservation laws which is violated due to loss of integrability. On the other hand, similarity solutions under the truncated LIA can be quite different to their counterparts found for the classical LIA, as they must obey a t1/3 type scaling rather than the t1/2 type scaling commonly found in the LIA and Biot-Savart dynamics. This change in similarity scaling means that Kelvin waves are radiated at a slower rate from vortex kinks formed after reconnection events. The loss of soliton solutions and the difference in similarity scaling indicate that dynamics emergent under

  5. The combination of i-leader truncation and gemcitabine improves oncolytic adenovirus efficacy in an immunocompetent model.

    Science.gov (United States)

    Puig-Saus, C; Laborda, E; Rodríguez-García, A; Cascalló, M; Moreno, R; Alemany, R

    2014-02-01

    Adenovirus (Ad) i-leader protein is a small protein of unknown function. The C-terminus truncation of the i-leader protein increases Ad release from infected cells and cytotoxicity. In the current study, we use the i-leader truncation to enhance the potency of an oncolytic Ad. In vitro, an i-leader truncated oncolytic Ad is released faster to the supernatant of infected cells, generates larger plaques, and is more cytotoxic in both human and Syrian hamster cell lines. In mice bearing human tumor xenografts, the i-leader truncation enhances oncolytic efficacy. However, in a Syrian hamster pancreatic tumor model, which is immunocompetent and less permissive to human Ad, antitumor efficacy is only observed when the i-leader truncated oncolytic Ad, but not the non-truncated version, is combined with gemcitabine. This synergistic effect observed in the Syrian hamster model was not seen in vitro or in immunodeficient mice bearing the same pancreatic hamster tumors, suggesting a role of the immune system in this synergism. These results highlight the interest of the i-leader C-terminus truncation because it enhances the antitumor potency of an oncolytic Ad and provides synergistic effects with gemcitabine in the presence of an immune competent system.

  6. Local and accumulated truncation errors in a class of perturbative numerical methods

    International Nuclear Information System (INIS)

    Adam, G.; Adam, S.; Corciovei, A.

    1980-01-01

    The approach to the solution of the radial Schroedinger equation using piecewise perturbative theory with a step function reference potential leads to a class of powerful numerical methods, conveniently abridged as SF-PNM(K), where K denotes the order at which the perturbation series was truncated. In the present paper rigorous results are given for the local truncation errors and bounds are derived for the accumulated truncated errors associated to SF-PNM(K), K = 0, 1, 2. They allow us to establish the smoothness conditions which have to be fulfilled by the potential in order to ensure a safe use of SF-PNM(K), and to understand the experimentally observed behaviour of the numerical results with the step size h. (author)

  7. Frequency interval balanced truncation of discrete-time bilinear systems

    DEFF Research Database (Denmark)

    Jazlan, Ahmad; Sreeram, Victor; Shaker, Hamid Reza

    2016-01-01

    This paper presents the development of a new model reduction method for discrete-time bilinear systems based on the balanced truncation framework. In many model reduction applications, it is advantageous to analyze the characteristics of the system with emphasis on particular frequency intervals...... are the solution to a pair of new generalized Lyapunov equations. The conditions for solvability of these new generalized Lyapunov equations are derived and a numerical solution method for solving these generalized Lyapunov equations is presented. Numerical examples which illustrate the usage of the new...... generalized frequency interval controllability and observability gramians as part of the balanced truncation framework are provided to demonstrate the performance of the proposed method....

  8. Adaptive bit plane quadtree-based block truncation coding for image compression

    Science.gov (United States)

    Li, Shenda; Wang, Jin; Zhu, Qing

    2018-04-01

    Block truncation coding (BTC) is a fast image compression technique applied in spatial domain. Traditional BTC and its variants mainly focus on reducing computational complexity for low bit rate compression, at the cost of lower quality of decoded images, especially for images with rich texture. To solve this problem, in this paper, a quadtree-based block truncation coding algorithm combined with adaptive bit plane transmission is proposed. First, the direction of edge in each block is detected using Sobel operator. For the block with minimal size, adaptive bit plane is utilized to optimize the BTC, which depends on its MSE loss encoded by absolute moment block truncation coding (AMBTC). Extensive experimental results show that our method gains 0.85 dB PSNR on average compare to some other state-of-the-art BTC variants. So it is desirable for real time image compression applications.

  9. Evidence for Truncated Exponential Probability Distribution of Earthquake Slip

    KAUST Repository

    Thingbaijam, Kiran Kumar; Mai, Paul Martin

    2016-01-01

    Earthquake ruptures comprise spatially varying slip on the fault surface, where slip represents the displacement discontinuity between the two sides of the rupture plane. In this study, we analyze the probability distribution of coseismic slip, which provides important information to better understand earthquake source physics. Although the probability distribution of slip is crucial for generating realistic rupture scenarios for simulation-based seismic and tsunami-hazard analysis, the statistical properties of earthquake slip have received limited attention so far. Here, we use the online database of earthquake source models (SRCMOD) to show that the probability distribution of slip follows the truncated exponential law. This law agrees with rupture-specific physical constraints limiting the maximum possible slip on the fault, similar to physical constraints on maximum earthquake magnitudes.We show the parameters of the best-fitting truncated exponential distribution scale with average coseismic slip. This scaling property reflects the control of the underlying stress distribution and fault strength on the rupture dimensions, which determines the average slip. Thus, the scale-dependent behavior of slip heterogeneity is captured by the probability distribution of slip. We conclude that the truncated exponential law accurately quantifies coseismic slip distribution and therefore allows for more realistic modeling of rupture scenarios. © 2016, Seismological Society of America. All rights reserverd.

  10. Evidence for Truncated Exponential Probability Distribution of Earthquake Slip

    KAUST Repository

    Thingbaijam, Kiran K. S.

    2016-07-13

    Earthquake ruptures comprise spatially varying slip on the fault surface, where slip represents the displacement discontinuity between the two sides of the rupture plane. In this study, we analyze the probability distribution of coseismic slip, which provides important information to better understand earthquake source physics. Although the probability distribution of slip is crucial for generating realistic rupture scenarios for simulation-based seismic and tsunami-hazard analysis, the statistical properties of earthquake slip have received limited attention so far. Here, we use the online database of earthquake source models (SRCMOD) to show that the probability distribution of slip follows the truncated exponential law. This law agrees with rupture-specific physical constraints limiting the maximum possible slip on the fault, similar to physical constraints on maximum earthquake magnitudes.We show the parameters of the best-fitting truncated exponential distribution scale with average coseismic slip. This scaling property reflects the control of the underlying stress distribution and fault strength on the rupture dimensions, which determines the average slip. Thus, the scale-dependent behavior of slip heterogeneity is captured by the probability distribution of slip. We conclude that the truncated exponential law accurately quantifies coseismic slip distribution and therefore allows for more realistic modeling of rupture scenarios. © 2016, Seismological Society of America. All rights reserverd.

  11. High-yield water-based synthesis of truncated silver nanocubes

    International Nuclear Information System (INIS)

    Chang, Yun-Min; Lu, I-Te; Chen, Chih-Yuan; Hsieh, Yu-Chi; Wu, Pu-Wei

    2014-01-01

    Highlights: • Development of a water-based formula to fabricate truncated Ag nanocubes. • The sample exhibits (1 0 0), (1 1 0), and (1 1 1) on the facets, edges, and corners. • The sample shows three characteristic absorption peaks due to plasma resonance. -- Abstract: A high-yield water-based hydrothermal synthesis was developed using silver nitrate, ammonia, glucose, and cetyltrimethylammonium bromide (CTAB) as precursors to synthesize truncated silver nanocubes with uniform sizes and in large quantities. With a fixed CTAB concentration, truncated silver nanocubes with sizes of 49.3 ± 4.1 nm were produced when the molar ratio of glucose/silver cation was maintained at 0.1. The sample exhibited (1 0 0), (1 1 0), and (1 1 1) planes on the facets, edges, and corners, respectively. In contrast, with a slightly larger glucose/silver cation ratio of 0.35, well-defined nanocubes with sizes of 70.9 ± 3.8 nm sizes were observed with the (1 0 0) plane on six facets. When the ratio was further increased to 1.5, excess reduction of silver cations facilitated the simultaneous formation of nanoparticles with cubic, spherical, and irregular shapes. Consistent results were obtained from transmission electron microscopy, scanning electron microscopy, X-ray diffraction, and UV–visible absorption measurements

  12. High-yield water-based synthesis of truncated silver nanocubes

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Yun-Min; Lu, I-Te; Chen, Chih-Yuan; Hsieh, Yu-Chi; Wu, Pu-Wei, E-mail: ppwu@mail.nctu.edu.tw

    2014-02-15

    Highlights: • Development of a water-based formula to fabricate truncated Ag nanocubes. • The sample exhibits (1 0 0), (1 1 0), and (1 1 1) on the facets, edges, and corners. • The sample shows three characteristic absorption peaks due to plasma resonance. -- Abstract: A high-yield water-based hydrothermal synthesis was developed using silver nitrate, ammonia, glucose, and cetyltrimethylammonium bromide (CTAB) as precursors to synthesize truncated silver nanocubes with uniform sizes and in large quantities. With a fixed CTAB concentration, truncated silver nanocubes with sizes of 49.3 ± 4.1 nm were produced when the molar ratio of glucose/silver cation was maintained at 0.1. The sample exhibited (1 0 0), (1 1 0), and (1 1 1) planes on the facets, edges, and corners, respectively. In contrast, with a slightly larger glucose/silver cation ratio of 0.35, well-defined nanocubes with sizes of 70.9 ± 3.8 nm sizes were observed with the (1 0 0) plane on six facets. When the ratio was further increased to 1.5, excess reduction of silver cations facilitated the simultaneous formation of nanoparticles with cubic, spherical, and irregular shapes. Consistent results were obtained from transmission electron microscopy, scanning electron microscopy, X-ray diffraction, and UV–visible absorption measurements.

  13. Intersection spaces, spatial homology truncation, and string theory

    CERN Document Server

    Banagl, Markus

    2010-01-01

    Intersection cohomology assigns groups which satisfy a generalized form of Poincaré duality over the rationals to a stratified singular space. The present monograph introduces a method that assigns to certain classes of stratified spaces cell complexes, called intersection spaces, whose ordinary rational homology satisfies generalized Poincaré duality. The cornerstone of the method is a process of spatial homology truncation, whose functoriality properties are analyzed in detail. The material on truncation is autonomous and may be of independent interest to homotopy theorists. The cohomology of intersection spaces is not isomorphic to intersection cohomology and possesses algebraic features such as perversity-internal cup-products and cohomology operations that are not generally available for intersection cohomology. A mirror-symmetric interpretation, as well as applications to string theory concerning massless D-branes arising in type IIB theory during a Calabi-Yau conifold transition, are discussed.

  14. The Apparent Lack of Lorentz Invariance in Zero-Point Fields with Truncated Spectra

    Directory of Open Access Journals (Sweden)

    Daywitt W. C.

    2009-01-01

    Full Text Available The integrals that describe the expectation values of the zero-point quantum-field-theoretic vacuum state are semi-infinite, as are the integrals for the stochastic electrodynamic vacuum. The unbounded upper limit to these integrals leads in turn to infinite energy densities and renormalization masses. A number of models have been put forward to truncate the integrals so that these densities and masses are finite. Unfortunately the truncation apparently destroys the Lorentz invariance of the integrals. This note argues that the integrals are naturally truncated by the graininess of the negative-energy Planck vacuum state from which the zero-point vacuum arises, and are thus automatically Lorentz invariant.

  15. Reduction of variable-truncation artifacts from beam occlusion during in situ x-ray tomography

    DEFF Research Database (Denmark)

    Borg, Leise; Jørgensen, Jakob Sauer; Frikel, Jürgen

    2017-01-01

    Many in situ x-ray tomography studies require experimental rigs which may partially occlude the beam and cause parts of the projection data to be missing. In a study of fluid flow in porous chalk using a percolation cell with four metal bars drastic streak artifacts arise in the filtered...... and artifact-reduction methods are designed in context of FBP reconstruction motivated by computational efficiency practical for large, real synchrotron data. While a specific variable-truncation case is considered, the proposed methods can be applied to general data cut-offs arising in different in situ x-ray...... backprojection (FBP) reconstruction at certain orientations. Projections with non-trivial variable truncation caused by the metal bars are the source of these variable-truncation artifacts. To understand the artifacts a mathematical model of variable-truncation data as a function of metal bar radius and distance...

  16. Propagation of a general-type beam through a truncated fractional Fourier transform optical system.

    Science.gov (United States)

    Zhao, Chengliang; Cai, Yangjian

    2010-03-01

    Paraxial propagation of a general-type beam through a truncated fractional Fourier transform (FRT) optical system is investigated. Analytical formulas for the electric field and effective beam width of a general-type beam in the FRT plane are derived based on the Collins formula. Our formulas can be used to study the propagation of a variety of laser beams--such as Gaussian, cos-Gaussian, cosh-Gaussian, sine-Gaussian, sinh-Gaussian, flat-topped, Hermite-cosh-Gaussian, Hermite-sine-Gaussian, higher-order annular Gaussian, Hermite-sinh-Gaussian and Hermite-cos-Gaussian beams--through a FRT optical system with or without truncation. The propagation properties of a Hermite-cos-Gaussian beam passing through a rectangularly truncated FRT optical system are studied as a numerical example. Our results clearly show that the truncated FRT optical system provides a convenient way for laser beam shaping.

  17. Functional analysis of Rift Valley fever virus NSs encoding a partial truncation.

    Science.gov (United States)

    Head, Jennifer A; Kalveram, Birte; Ikegami, Tetsuro

    2012-01-01

    Rift Valley fever virus (RVFV), belongs to genus Phlebovirus of the family Bunyaviridae, causes high rates of abortion and fetal malformation in infected ruminants as well as causing neurological disorders, blindness, or lethal hemorrhagic fever in humans. RVFV is classified as a category A priority pathogen and a select agent in the U.S., and currently there are no therapeutics available for RVF patients. NSs protein, a major virulence factor of RVFV, inhibits host transcription including interferon (IFN)-β mRNA synthesis and promotes degradation of dsRNA-dependent protein kinase (PKR). NSs self-associates at the C-terminus 17 aa., while NSs at aa.210-230 binds to Sin3A-associated protein (SAP30) to inhibit the activation of IFN-β promoter. Thus, we hypothesize that NSs function(s) can be abolished by truncation of specific domains, and co-expression of nonfunctional NSs with intact NSs will result in the attenuation of NSs function by dominant-negative effect. Unexpectedly, we found that RVFV NSs truncated at aa. 6-30, 31-55, 56-80, 81-105, 106-130, 131-155, 156-180, 181-205, 206-230, 231-248 or 249-265 lack functions of IFN-β mRNA synthesis inhibition and degradation of PKR. Truncated NSs were less stable in infected cells, while nuclear localization was inhibited in NSs lacking either of aa.81-105, 106-130, 131-155, 156-180, 181-205, 206-230 or 231-248. Furthermore, none of truncated NSs had exhibited significant dominant-negative functions for NSs-mediated IFN-β suppression or PKR degradation upon co-expression in cells infected with RVFV. We also found that any of truncated NSs except for intact NSs does not interact with RVFV NSs even in the presence of intact C-terminus self-association domain. Our results suggest that conformational integrity of NSs is important for the stability, cellular localization and biological functions of RVFV NSs, and the co-expression of truncated NSs does not exhibit dominant-negative phenotype.

  18. Functional analysis of Rift Valley fever virus NSs encoding a partial truncation.

    Directory of Open Access Journals (Sweden)

    Jennifer A Head

    Full Text Available Rift Valley fever virus (RVFV, belongs to genus Phlebovirus of the family Bunyaviridae, causes high rates of abortion and fetal malformation in infected ruminants as well as causing neurological disorders, blindness, or lethal hemorrhagic fever in humans. RVFV is classified as a category A priority pathogen and a select agent in the U.S., and currently there are no therapeutics available for RVF patients. NSs protein, a major virulence factor of RVFV, inhibits host transcription including interferon (IFN-β mRNA synthesis and promotes degradation of dsRNA-dependent protein kinase (PKR. NSs self-associates at the C-terminus 17 aa., while NSs at aa.210-230 binds to Sin3A-associated protein (SAP30 to inhibit the activation of IFN-β promoter. Thus, we hypothesize that NSs function(s can be abolished by truncation of specific domains, and co-expression of nonfunctional NSs with intact NSs will result in the attenuation of NSs function by dominant-negative effect. Unexpectedly, we found that RVFV NSs truncated at aa. 6-30, 31-55, 56-80, 81-105, 106-130, 131-155, 156-180, 181-205, 206-230, 231-248 or 249-265 lack functions of IFN-β mRNA synthesis inhibition and degradation of PKR. Truncated NSs were less stable in infected cells, while nuclear localization was inhibited in NSs lacking either of aa.81-105, 106-130, 131-155, 156-180, 181-205, 206-230 or 231-248. Furthermore, none of truncated NSs had exhibited significant dominant-negative functions for NSs-mediated IFN-β suppression or PKR degradation upon co-expression in cells infected with RVFV. We also found that any of truncated NSs except for intact NSs does not interact with RVFV NSs even in the presence of intact C-terminus self-association domain. Our results suggest that conformational integrity of NSs is important for the stability, cellular localization and biological functions of RVFV NSs, and the co-expression of truncated NSs does not exhibit dominant-negative phenotype.

  19. Truncated Dual-Cap Nucleation Site Development

    Science.gov (United States)

    Matson, Douglas M.; Sander, Paul J.

    2012-01-01

    During heterogeneous nucleation within a metastable mushy-zone, several geometries for nucleation site development must be considered. Traditional spherical dual cap and crevice models are compared to a truncated dual cap to determine the activation energy and critical cluster growth kinetics in ternary Fe-Cr-Ni steel alloys. Results of activation energy results indicate that nucleation is more probable at grain boundaries within the solid than at the solid-liquid interface.

  20. Insecticides resistance in the Culex quinquefasciatus populations from northern Thailand and possible resistance mechanisms.

    Science.gov (United States)

    Yanola, Jintana; Chamnanya, Saowanee; Lumjuan, Nongkran; Somboon, Pradya

    2015-09-01

    The mosquito vector Culex quinquefasciatus is known to be resistant to insecticides worldwide, including Thailand. This study was the first investigation of the insecticide resistance mechanisms, involving metabolic detoxification and target site insensitivity in C. quinquefasciatus from Thailand. Adult females reared from field-caught larvae from six provinces of northern Thailand were determined for resistant status by exposing to 0.05% deltamethrin, 0.75% permethrin and 5% malathion papers using the standard WHO susceptibility test. The overall mortality rates were 45.8%, 11.4% and 80.2%, respectively. A fragment of voltage-gated sodium channel gene was amplified and sequenced to identify the knock down resistance (kdr) mutation. The ace-1 gene mutation was determined by using PCR-RFLP. The L1014F kdr mutation was observed in all populations, but the homozygous mutant F/F1014 genotype was found only in two of the six provinces where the kdr mutation was significantly correlated with deltamethrin resistance. However, none of mosquitoes had the G119S mutation in the ace-1 gene. A laboratory deltamethrin resistant strain, Cq_CM_R, has been established showing a highly resistant level after selection for a few generations. The mutant F1014 allele frequency was significantly increased after one generation of selection. A synergist assay was performed to assess the metabolic detoxifying enzymes. Addition of bis(4-nitrophenyl)-phosphate (BNPP) and diethyl maleate (DEM), inhibitors of esterases and glutathione S-transferases (GST), respectively, into the larval bioassay of the Cq_CM strain with deltamethrin showed no significant reduction. By contrast, addition of piperonyl butoxide (PBO), an inhibitor of cytochrome P450 monooxygenases, showed a 9-fold reduction of resistance. Resistance to pyrethroids in C. quinquefasciatus is widely distributed in northern Thailand. This study reports for the first time for the detection of the L1014F kdr mutation in wild populations

  1. Role of Cdx and Hox genes in posterior axial extension in the mouse

    NARCIS (Netherlands)

    Young, T.

    2009-01-01

    Hox and Cdx genes are phylogenetically related transcription factor-encoding genes that control positional tissue identity during embryonic develop- ment. In addition, mutations impairing Cdx activity in mice elicit poste- rior body truncations, affecting the axial skeleton, the neuraxis and cau-

  2. Varying coefficient subdistribution regression for left-truncated semi-competing risks data.

    Science.gov (United States)

    Li, Ruosha; Peng, Limin

    2014-10-01

    Semi-competing risks data frequently arise in biomedical studies when time to a disease landmark event is subject to dependent censoring by death, the observation of which however is not precluded by the occurrence of the landmark event. In observational studies, the analysis of such data can be further complicated by left truncation. In this work, we study a varying co-efficient subdistribution regression model for left-truncated semi-competing risks data. Our method appropriately accounts for the specifical truncation and censoring features of the data, and moreover has the flexibility to accommodate potentially varying covariate effects. The proposed method can be easily implemented and the resulting estimators are shown to have nice asymptotic properties. We also present inference, such as Kolmogorov-Smirnov type and Cramér Von-Mises type hypothesis testing procedures for the covariate effects. Simulation studies and an application to the Denmark diabetes registry demonstrate good finite-sample performance and practical utility of the proposed method.

  3. Symmetric truncations of the shallow-water equations

    International Nuclear Information System (INIS)

    Rouhi, A.; Abarbanel, H.D.I.

    1993-01-01

    Conservation of potential vorticity in Eulerian fluids reflects particle interchange symmetry in the Lagrangian fluid version of the same theory. The algebra associated with this symmetry in the shallow-water equations is studied here, and we give a method for truncating the degrees of freedom of the theory which preserves a maximal number of invariants associated with this algebra. The finite-dimensional symmetry associated with keeping only N modes of the shallow-water flow is SU(N). In the limit where the number of modes goes to infinity (N→∞) all the conservation laws connected with potential vorticity conservation are recovered. We also present a Hamiltonian which is invariant under this truncated symmetry and which reduces to the familiar shallow-water Hamiltonian when N→∞. All this provides a finite-dimensional framework for numerical work with the shallow-water equations which preserves not only energy and enstrophy but all other known conserved quantities consistent with the finite number of degrees of freedom. The extension of these ideas to other nearly two-dimensional flows is discussed

  4. Periodic expression of nuclear and mitochondrial DNA replication genes during the trypanosomatid cell cycle.

    Science.gov (United States)

    Pasion, S G; Brown, G W; Brown, L M; Ray, D S

    1994-12-01

    In trypanosomatids, DNA replication in the nucleus and in the single mitochondrion (or kinetoplast) initiates nearly simultaneously, suggesting that the DNA synthesis (S) phases of the nucleus and the mitochondrion are coordinately regulated. To investigate the basis for the temporal link between nuclear and mitochondrial DNA synthesis phases the expression of the genes encoding DNA ligase I, the 51 and 28 kDa subunits of replication protein A, dihydrofolate reductase and the mitochondrial type II topoisomerase were analyzed during the cell cycle progression of synchronous cultures of Crithidia fasciculata. These DNA replication genes were all expressed periodically, with peak mRNA levels occurring just prior to or at the peak of DNA synthesis in the synchronized cultures. A plasmid clone (pdN-1) in which TOP2, the gene encoding the mitochondrial topoisomerase, was disrupted by the insertion of a NEO drug-resistance cassette was found to express both a truncated TOP2 mRNA and a truncated topoisomerase polypeptide. The truncated mRNA was also expressed periodically coordinate with the expression of the endogenous TOP2 mRNA indicating that cis elements necessary for periodic expression are contained within cloned sequences. The expression of both TOP2 and nuclear DNA replication genes at the G1/S boundary suggests that regulated expression of these genes may play a role in coordinating nuclear and mitochondrial S phases in trypanosomatids.

  5. Truncation of Gal4p explains the inactivation of the GAL/MEL regulon in both Saccharomyces bayanus and some Saccharomyces cerevisiae wine strains.

    Science.gov (United States)

    Dulermo, Rémi; Legras, Jean-Luc; Brunel, François; Devillers, Hugo; Sarilar, Véronique; Neuvéglise, Cécile; Nguyen, Huu-Vang

    2016-09-01

    In the past, the galactose-negative (Gal(-)) phenotype was a key physiological character used to distinguish Saccharomyces bayanus from S. cerevisiae In this work, we investigated the inactivation of GAL gene networks in S. bayanus, which is an S. uvarum/S. eubayanus hybrid, and in S. cerevisiae wine strains erroneously labelled 'S. bayanus'. We made an inventory of their GAL genes using genomes that were either available publicly, re-sequenced by us, or assembled from public data and completed with targeted sequencing. In the S. eubayanus/S. uvarum CBS 380(T) hybrid, the GAL/MEL network is composed of genes from both parents: from S. uvarum, an otherwise complete set that lacks GAL4, and from S. eubayanus, a truncated version of GAL4 and an additional copy of GAL3 and GAL80 Similarly, two different truncated GAL4 alleles were found in S. cerevisiae wine strains EC1118 and LalvinQA23. The lack of GAL4 activity in these strains was corrected by introducing a full-length copy of S. cerevisiae GAL4 on a CEN4/ARS plasmid. Transformation with this plasmid restored galactose utilisation in Gal(-) strains, and melibiose fermentation in strain CBS 380(T) The melibiose fermentation phenotype, formerly regarded as characteristic of S. uvarum, turned out to be widespread among Saccharomyces species. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Autocorrelation as a source of truncated Lévy flights in foreign exchange rates

    Science.gov (United States)

    Figueiredo, Annibal; Gleria, Iram; Matsushita, Raul; Da Silva, Sergio

    2003-05-01

    We suggest that the ultraslow speed of convergence associated with truncated Lévy flights (Phys. Rev. Lett. 73 (1994) 2946) may well be explained by autocorrelations in data. We show how a particular type of autocorrelation generates power laws consistent with a truncated Lévy flight. Stock exchanges have been suggested to be modeled by a truncated Lévy flight (Nature 376 (1995) 46; Physica A 297 (2001) 509; Econom. Bull. 7 (2002) 1). Here foreign exchange rate data are taken instead. Scaling power laws in the “probability of return to the origin” are shown to emerge for most currencies. A novel approach to measure how distant a process is from a Gaussian regime is presented.

  7. No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk: implications for gene panel testing

    OpenAIRE

    Easton, Douglas Frederick; Lesueur, Fabienne; Decker, Brennan; Michailidou, Kyriaki; Li, Jun; Allen, Jamie; Luccarini, Craig; Pooley, Karen Anne; Shah, Mitulkumar Nandlal; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Ahmad, Jamil; Thompson, Ella R; Damiola, Francesca

    2016-01-01

    Background BRCA1 interacting protein C-terminal helicase 1 (BRIP1) is one of the Fanconi Anaemia Complementation (FANC) group family of DNA repair proteins. Biallelic mutations in BRIP1 are responsible for FANC group J, and previous studies have also suggested that rare protein truncating variants in BRIP1 are associated with an increased risk of breast cancer. These studies have led to inclusion of BRIP1 on targeted sequencing panels for breast cancer risk prediction. Metho...

  8. A Residual Approach for Balanced Truncation Model Reduction (BTMR of Compartmental Systems

    Directory of Open Access Journals (Sweden)

    William La Cruz

    2014-05-01

    Full Text Available This paper presents a residual approach of the square root balanced truncation algorithm for model order reduction of continuous, linear and time-invariante compartmental systems. Specifically, the new approach uses a residual method to approximate the controllability and observability gramians, whose resolution is an essential step of the square root balanced truncation algorithm, that requires a great computational cost. Numerical experiences are included to highlight the efficacy of the proposed approach.

  9. Rotating D0-branes and consistent truncations of supergravity

    International Nuclear Information System (INIS)

    Anabalón, Andrés; Ortiz, Thomas; Samtleben, Henning

    2013-01-01

    The fluctuations around the D0-brane near-horizon geometry are described by two-dimensional SO(9) gauged maximal supergravity. We work out the U(1) 4 truncation of this theory whose scalar sector consists of five dilaton and four axion fields. We construct the full non-linear Kaluza–Klein ansatz for the embedding of the dilaton sector into type IIA supergravity. This yields a consistent truncation around a geometry which is the warped product of a two-dimensional domain wall and the sphere S 8 . As an application, we consider the solutions corresponding to rotating D0-branes which in the near-horizon limit approach AdS 2 ×M 8 geometries, and discuss their thermodynamical properties. More generally, we study the appearance of such solutions in the presence of non-vanishing axion fields

  10. Two truncating USH3A mutations, including one novel, in a German family with Usher syndrome.

    Science.gov (United States)

    Ebermann, Inga; Wilke, Robert; Lauhoff, Thomas; Lübben, Dirk; Zrenner, Eberhart; Bolz, Hanno Jörn

    2007-08-30

    To identify the genetic defect in a German family with Usher syndrome (USH) and linkage to the USH3A locus. DNA samples of five family members (both parents and the three patients) were genotyped with polymorphic microsatellite markers specific for eight USH genes. Three affected family members underwent detailed ocular and audiologic characterization. Symptoms in the patients were compatible with Usher syndrome and show intrafamilial variation, for both hearing loss (ranging from severe to profound with non-linear progression) and vision. Genotyping of microsatellite markers for the different USH loci was in line with a defect in the USH3A gene on chromosome 3q25. Sequence analysis of the USH3A gene revealed two truncating mutations; c.149_152delCAGGinsTGTCCAAT, which has been described previously, and a novel mutation, c.502_503insA, segregating with the phenotype. To date, only 11 USH3A mutations have been described. This is the first description of a German family with USH due to USH3A mutations, including one novel. Our findings indicate that also in the Central European population, USH3A mutations should be considered in cases of USH.

  11. A protein-truncating R179X variant in RNF186 confers protection against ulcerative colitis

    NARCIS (Netherlands)

    Rivas, Manuel A.; Graham, Daniel; Sulem, Patrick; Stevens, Christine; Desch, A. Nicole; Goyette, Philippe; Gudbjartsson, Daniel; Jonsdottir, Ingileif; Thorsteinsdottir, Unnur; Degenhardt, Frauke; Mucha, Soeren; Kurki, Mitja I.; Li, Dalin; D'Amato, Mauro; Annese, Vito; Vermeire, Severine; Weersma, Rinse K.; Halfvarson, Jonas; Paavola-Sakki, Paulina; Lappalainen, Maarit; Lek, Monkol; Cummings, Beryl; Tukiainen, Taru; Haritunians, Talin; Halme, Leena; Koskinen, Lotta L. E.; Ananthakrishnan, Ashwin N.; Luo, Yang; Heap, Graham A.; Visschedijk, Marijn C.; MacArthur, Daniel G.; Neale, Benjamin M.; Ahmad, Tariq; Anderson, Carl A.; Brant, Steven R.; Duerr, Richard H.; Silverberg, Mark S.; Cho, Judy H.; Palotie, Aarno; Saavalainen, Paivi; Kontula, Kimmo; Farkkila, Martti; McGovern, Dermot P. B.; Franke, Andre; Stefansson, Kari; Rioux, John D.; Xavier, Ramnik J.; Daly, Mark J.

    Protein-truncating variants protective against human disease provide in vivo validation of therapeutic targets. Here we used targeted sequencing to conduct a search for protein-truncating variants conferring protection against inflammatory bowel disease exploiting knowledge of common variants

  12. A min cut-set-wise truncation procedure for importance measures computation in probabilistic safety assessment

    Energy Technology Data Exchange (ETDEWEB)

    Duflot, Nicolas [Universite de technologie de Troyes, Institut Charles Delaunay/LM2S, FRE CNRS 2848, 12, rue Marie Curie, BP2060, F-10010 Troyes cedex (France)], E-mail: nicolas.duflot@areva.com; Berenguer, Christophe [Universite de technologie de Troyes, Institut Charles Delaunay/LM2S, FRE CNRS 2848, 12, rue Marie Curie, BP2060, F-10010 Troyes cedex (France)], E-mail: christophe.berenguer@utt.fr; Dieulle, Laurence [Universite de technologie de Troyes, Institut Charles Delaunay/LM2S, FRE CNRS 2848, 12, rue Marie Curie, BP2060, F-10010 Troyes cedex (France)], E-mail: laurence.dieulle@utt.fr; Vasseur, Dominique [EPSNA Group (Nuclear PSA and Application), EDF Research and Development, 1, avenue du Gal de Gaulle, 92141 Clamart cedex (France)], E-mail: dominique.vasseur@edf.fr

    2009-11-15

    A truncation process aims to determine among the set of minimal cut-sets (MCS) produced by a probabilistic safety assessment (PSA) model which of them are significant. Several truncation processes have been proposed for the evaluation of the probability of core damage ensuring a fixed accuracy level. However, the evaluation of new risk indicators as importance measures requires to re-examine the truncation process in order to ensure that the produced estimates will be accurate enough. In this paper a new truncation process is developed permitting to estimate from a single set of MCS the importance measure of any basic event with the desired accuracy level. The main contribution of this new method is to propose an MCS-wise truncation criterion involving two thresholds: an absolute threshold in addition to a new relative threshold concerning the potential probability of the MCS of interest. The method has been tested on a complete level 1 PSA model of a 900 MWe NPP developed by 'Electricite de France' (EDF) and the results presented in this paper indicate that to reach the same accuracy level the proposed method produces a set of MCS whose size is significantly reduced.

  13. A min cut-set-wise truncation procedure for importance measures computation in probabilistic safety assessment

    International Nuclear Information System (INIS)

    Duflot, Nicolas; Berenguer, Christophe; Dieulle, Laurence; Vasseur, Dominique

    2009-01-01

    A truncation process aims to determine among the set of minimal cut-sets (MCS) produced by a probabilistic safety assessment (PSA) model which of them are significant. Several truncation processes have been proposed for the evaluation of the probability of core damage ensuring a fixed accuracy level. However, the evaluation of new risk indicators as importance measures requires to re-examine the truncation process in order to ensure that the produced estimates will be accurate enough. In this paper a new truncation process is developed permitting to estimate from a single set of MCS the importance measure of any basic event with the desired accuracy level. The main contribution of this new method is to propose an MCS-wise truncation criterion involving two thresholds: an absolute threshold in addition to a new relative threshold concerning the potential probability of the MCS of interest. The method has been tested on a complete level 1 PSA model of a 900 MWe NPP developed by 'Electricite de France' (EDF) and the results presented in this paper indicate that to reach the same accuracy level the proposed method produces a set of MCS whose size is significantly reduced.

  14. Lymphoscintigraphy for sentinel lymph node detection in breast cancer: usefulness of image truncation

    International Nuclear Information System (INIS)

    Carrier, P.; Remp, H.J.; Chaborel, J.P.; Lallement, M.; Bussiere, F.; Darcourt, J.; Lallement, M.; Leblanc-Talent, P.; Machiavello, J.C.; Ettore, F.

    2004-01-01

    The sentinel lymph node (SNL) detection in breast cancer has been recently validated. It allows the reduction of the number of axillary dissections and their corresponding side effects. We tested a simple method of image truncation in order to improve the sensitivity of lymphoscintigraphy. This approach is justified by the magnitude of uptake difference between the injection site and the SNL. We prospectively investigated SNL detection using a triple method (lymphoscintigraphy, blue dye and surgical radio detection) in 130 patients. SNL was identified in 104 of the 132 patients (80%) using the standard images and in 126 of them (96, 9%) using the truncated images. Blue dye detection and surgical radio detection had a sensitivity of 76,9% and 98,5% respectively. The false negative rate was 10,3%. 288 SNL were dissected, 31 were metastatic. Among the 19 patients with metastatic SNL and more than one SNL detected, the metastatic SNL was not the hottest in 9 of them. 28 metastatic SNL were detected Y on truncated images versus only 19 on standard images. Truncation which dramatically increases the sensitivity of lymphoscintigraphy allows to increase the number of dissected SNL and probably reduces the false negative rate. (author)

  15. Truncated forms of viral VP2 proteins fused to EGFP assemble into fluorescent parvovirus-like particles

    Directory of Open Access Journals (Sweden)

    Vuento Matti

    2006-12-01

    Full Text Available Abstract Fluorescence correlation spectroscopy (FCS monitors random movements of fluorescent molecules in solution, giving information about the number and the size of for example nano-particles. The canine parvovirus VP2 structural protein as well as N-terminal deletion mutants of VP2 (-14, -23, and -40 amino acids were fused to the C-terminus of the enhanced green fluorescent protein (EGFP. The proteins were produced in insect cells, purified, and analyzed by western blotting, confocal and electron microscopy as well as FCS. The non-truncated form, EGFP-VP2, diffused with a hydrodynamic radius of 17 nm, whereas the fluorescent mutants truncated by 14, 23 and 40 amino acids showed hydrodynamic radii of 7, 20 and 14 nm, respectively. These results show that the non-truncated EGFP-VP2 fusion protein and the EGFP-VP2 constructs truncated by 23 and by as much as 40 amino acids were able to form virus-like particles (VLPs. The fluorescent VLP, harbouring VP2 truncated by 23 amino acids, showed a somewhat larger hydrodynamic radius compared to the non-truncated EGFP-VP2. In contrast, the construct containing EGFP-VP2 truncated by 14 amino acids was not able to assemble into VLP-resembling structures. Formation of capsid structures was confirmed by confocal and electron microscopy. The number of fluorescent fusion protein molecules present within the different VLPs was determined by FCS. In conclusion, FCS provides a novel strategy to analyze virus assembly and gives valuable structural information for strategic development of parvovirus-like particles.

  16. Molecular genetics of the Usher syndrome in Lebanon: identification of 11 novel protein truncating mutations by whole exome sequencing.

    Science.gov (United States)

    Reddy, Ramesh; Fahiminiya, Somayyeh; El Zir, Elie; Mansour, Ahmad; Megarbane, Andre; Majewski, Jacek; Slim, Rima

    2014-01-01

    Usher syndrome (USH) is a genetically heterogeneous condition with ten disease-causing genes. The spectrum of genes and mutations causing USH in the Lebanese and Middle Eastern populations has not been described. Consequently, diagnostic approaches designed to screen for previously reported mutations were unlikely to identify the mutations in 11 unrelated families, eight of Lebanese and three of Middle Eastern origins. In addition, six of the ten USH genes consist of more than 20 exons, each, which made mutational analysis by Sanger sequencing of PCR-amplified exons from genomic DNA tedious and costly. The study was aimed at the identification of USH causing genes and mutations in 11 unrelated families with USH type I or II. Whole exome sequencing followed by expanded familial validation by Sanger sequencing. We identified disease-causing mutations in all the analyzed patients in four USH genes, MYO7A, USH2A, GPR98 and CDH23. Eleven of the mutations were novel and protein truncating, including a complex rearrangement in GPR98. Our data highlight the genetic diversity of Usher syndrome in the Lebanese population and the time and cost-effectiveness of whole exome sequencing approach for mutation analysis of genetically heterogeneous conditions caused by large genes.

  17. Molecular genetics of the Usher syndrome in Lebanon: identification of 11 novel protein truncating mutations by whole exome sequencing.

    Directory of Open Access Journals (Sweden)

    Ramesh Reddy

    Full Text Available Usher syndrome (USH is a genetically heterogeneous condition with ten disease-causing genes. The spectrum of genes and mutations causing USH in the Lebanese and Middle Eastern populations has not been described. Consequently, diagnostic approaches designed to screen for previously reported mutations were unlikely to identify the mutations in 11 unrelated families, eight of Lebanese and three of Middle Eastern origins. In addition, six of the ten USH genes consist of more than 20 exons, each, which made mutational analysis by Sanger sequencing of PCR-amplified exons from genomic DNA tedious and costly. The study was aimed at the identification of USH causing genes and mutations in 11 unrelated families with USH type I or II.Whole exome sequencing followed by expanded familial validation by Sanger sequencing.We identified disease-causing mutations in all the analyzed patients in four USH genes, MYO7A, USH2A, GPR98 and CDH23. Eleven of the mutations were novel and protein truncating, including a complex rearrangement in GPR98.Our data highlight the genetic diversity of Usher syndrome in the Lebanese population and the time and cost-effectiveness of whole exome sequencing approach for mutation analysis of genetically heterogeneous conditions caused by large genes.

  18. Molecular Genetics of the Usher Syndrome in Lebanon: Identification of 11 Novel Protein Truncating Mutations by Whole Exome Sequencing

    Science.gov (United States)

    Reddy, Ramesh; Fahiminiya, Somayyeh; El Zir, Elie; Mansour, Ahmad; Megarbane, Andre; Majewski, Jacek; Slim, Rima

    2014-01-01

    Background Usher syndrome (USH) is a genetically heterogeneous condition with ten disease-causing genes. The spectrum of genes and mutations causing USH in the Lebanese and Middle Eastern populations has not been described. Consequently, diagnostic approaches designed to screen for previously reported mutations were unlikely to identify the mutations in 11 unrelated families, eight of Lebanese and three of Middle Eastern origins. In addition, six of the ten USH genes consist of more than 20 exons, each, which made mutational analysis by Sanger sequencing of PCR-amplified exons from genomic DNA tedious and costly. The study was aimed at the identification of USH causing genes and mutations in 11 unrelated families with USH type I or II. Methods Whole exome sequencing followed by expanded familial validation by Sanger sequencing. Results We identified disease-causing mutations in all the analyzed patients in four USH genes, MYO7A, USH2A, GPR98 and CDH23. Eleven of the mutations were novel and protein truncating, including a complex rearrangement in GPR98. Conclusion Our data highlight the genetic diversity of Usher syndrome in the Lebanese population and the time and cost-effectiveness of whole exome sequencing approach for mutation analysis of genetically heterogeneous conditions caused by large genes. PMID:25211151

  19. Fluorometric graphene oxide-based detection of Salmonella enteritis using a truncated DNA aptamer.

    Science.gov (United States)

    Chinnappan, Raja; AlAmer, Saleh; Eissa, Shimaa; Rahamn, Anas Abdel; Abu Salah, Khalid M; Zourob, Mohammed

    2017-12-18

    The work describes a fluorescence-based study for mapping the highest affinity truncated aptamer from the full length sequence and its integration in a graphene oxide platform for the detection of Salmonella enteriditis. To identify the best truncated sequence, molecular beacons and a displacement assay design are applied. In the fluorescence displacement assay, the truncated aptamer was hybridized with fluorescein and quencher-labeled complementary sequences to form a fluorescence/quencher pair. In the presence of S. enteritidis, the aptamer dissociates from the complementary labeled oligonucleotides and thus, the fluorescein/quencher pair becomes physically separated. This leads to an increase in fluorescence intensity. One of the truncated aptamers identified has a 2-fold lower dissociation constant (3.2 nM) compared to its full length aptamer (6.3 nM). The truncated aptamer selected in this process was used to develop a fluorometric graphene oxide (GO) based assay. If fluorescein-labeled aptamer is adsorbed on GO via π stacking interaction, fluorescence is quenched. However, in the presence of target (S. enteriditis), the labeled aptamers is released from surface to form a stable complex with the bacteria and fluorescence is restored, depending on the quantity of bacteria being present. The resulting assay has an unsurpassed detection limit of 25 cfu·mL -1 in the best case. The cross reactivity to Salmonella typhimurium, Staphylococcus aureus and Escherichia coli is negligible. The assay was applied to analyze doped milk samples for and gave good recovery. Thus, we believe that the truncated aptamer/graphene oxide platform is a potential tool for the detection of S. Enteritidis. Graphical abstract Fluorescently labelled aptamer against Salmonella enteritidis was adsorbed on the surface of graphene oxide by π-stacking interaction. This results in quenching of the fluorescence of the label. Addition of Salmonella enteritidis restores fluorescence, and this

  20. Error bounds for augmented truncations of discrete-time block-monotone Markov chains under subgeometric drift conditions

    OpenAIRE

    Masuyama, Hiroyuki

    2015-01-01

    This paper studies the last-column-block-augmented northwest-corner truncation (LC-block-augmented truncation, for short) of discrete-time block-monotone Markov chains under subgeometric drift conditions. The main result of this paper is to present an upper bound for the total variation distance between the stationary probability vectors of a block-monotone Markov chain and its LC-block-augmented truncation. The main result is extended to Markov chains that themselves may not be block monoton...

  1. Analytic Method for Pressure Recovery in Truncated Diffusers ...

    African Journals Online (AJOL)

    A prediction method is presented for the static pressure recovery in subsonic axisymmetric truncated conical diffusers. In the analysis, a turbulent boundary layer is assumed at the diffuser inlet and a potential core exists throughout the flow. When flow separation occurs, this approach cannot be used to predict the maximum ...

  2. Rotating D0-branes and consistent truncations of supergravity

    Energy Technology Data Exchange (ETDEWEB)

    Anabalón, Andrés [Departamento de Ciencias, Facultad de Artes Liberales, Facultad de Ingeniería y Ciencias, Universidad Adolfo Ibáñez, Av. Padre Hurtado 750, Viña del Mar (Chile); Université de Lyon, Laboratoire de Physique, UMR 5672, CNRS École Normale Supérieure de Lyon 46, allée d' Italie, F-69364 Lyon cedex 07 (France); Ortiz, Thomas; Samtleben, Henning [Université de Lyon, Laboratoire de Physique, UMR 5672, CNRS École Normale Supérieure de Lyon 46, allée d' Italie, F-69364 Lyon cedex 07 (France)

    2013-12-18

    The fluctuations around the D0-brane near-horizon geometry are described by two-dimensional SO(9) gauged maximal supergravity. We work out the U(1){sup 4} truncation of this theory whose scalar sector consists of five dilaton and four axion fields. We construct the full non-linear Kaluza–Klein ansatz for the embedding of the dilaton sector into type IIA supergravity. This yields a consistent truncation around a geometry which is the warped product of a two-dimensional domain wall and the sphere S{sup 8}. As an application, we consider the solutions corresponding to rotating D0-branes which in the near-horizon limit approach AdS{sub 2}×M{sub 8} geometries, and discuss their thermodynamical properties. More generally, we study the appearance of such solutions in the presence of non-vanishing axion fields.

  3. Progranulin modulates zebrafish motoneuron development in vivo and rescues truncation defects associated with knockdown of Survival motor neuron 1

    Directory of Open Access Journals (Sweden)

    Bateman Andrew

    2010-10-01

    Full Text Available Abstract Background Progranulin (PGRN encoded by the GRN gene, is a secreted glycoprotein growth factor that has been implicated in many physiological and pathophysiological processes. PGRN haploinsufficiency caused by autosomal dominant mutations within the GRN gene leads to progressive neuronal atrophy in the form of frontotemporal lobar degeneration (FTLD. This form of the disease is associated with neuronal inclusions that bear the ubiquitinated TAR DNA Binding Protein-43 (TDP-43 molecular signature (FTLD-U. The neurotrophic properties of PGRN in vitro have recently been reported but the role of PGRN in neurons is not well understood. Here we document the neuronal expression and functions of PGRN in spinal cord motoneuron (MN maturation and branching in vivo using zebrafish, a well established model of vertebrate embryonic development. Results Whole-mount in situ hybridization and immunohistochemical analyses of zebrafish embryos revealed that zfPGRN-A is expressed within the peripheral and central nervous systems including the caudal primary (CaP MNs within the spinal cord. Knockdown of zfPGRN-A mRNA translation mediated by antisense morpholino oligonucleotides disrupted normal CaP MN development resulting in both truncated MNs and inappropriate early branching. Ectopic over-expression of zfPGRN-A mRNA resulted in increased MN branching and rescued the truncation defects brought about by knockdown of zfPGRN-A expression. The ability of PGRN to interact with established MN developmental pathways was tested. PGRN over-expression was found to reverse the truncation defect resulting from knockdown of Survival of motor neuron 1 (smn1. This is involved in small ribonucleoprotein biogenesis RNA processing, mutations of which cause Spinal Muscular Atrophy (SMA in humans. It did not reverse the MN defects caused by interfering with the neuronal guidance pathway by knockdown of expression of NRP-1, a semaphorin co-receptor. Conclusions Expression of

  4. Generation of truncated recombinant form of tumor necrosis factor ...

    African Journals Online (AJOL)

    7. Original Research Article. Generation of truncated recombinant form of tumor necrosis factor ... as 6×His tagged using E.coli BL21 (DE3) expression system. The protein was ... proapoptotic signaling cascade through TNFR1. [5] which is ...

  5. Truncated C-terminus of fibrillin-1 induces Marfanoid-progeroid-lipodystrophy (MPL) syndrome in rabbit.

    Science.gov (United States)

    Chen, Mao; Yao, Bing; Yang, Qiangbing; Deng, Jichao; Song, Yuning; Sui, Tingting; Zhou, Lina; Yao, HaoBing; Xu, Yuanyuan; Ouyang, Hongsheng; Pang, Daxin; Li, Zhanjun; Lai, Liangxue

    2018-04-09

    Various clinical differences have been observed between patients with the FBN1 gene mutation and those with the classical Marfan phenotype. Although FBN1 knockout (KO) or dominant-negative mutant mice are widely used as an animal model for Marfan syndrome (MFS), these mice cannot recapitulate the genotype/phenotype relationship of Marfanoid-progeroid-lipodystrophy (MPL) syndrome, which is caused by a mutation in the C-terminus of fibrillin-1, the penultimate exon of the FBN1 gene. Here, we describe the generation of a rabbit MPL model with C-terminal truncation of fibrillin-1 using a CRISPR/Cas9 system. FBN1 heterozygous ( FBN1 Het) rabbits faithfully recapitulated the phenotypes of MFS, including muscle wasting and impaired connective tissue, ocular syndrome and aortic dilation. Moreover, skin symptoms, lipodystrophy, growth retardation and dysglycemia were also seen in these FBN1 Het rabbits, and have not been reported in other animal models. In conclusion, this novel rabbit model mimics the histopathological changes and functional defects of MPL syndrome, and could become a valuable model for studies of pathogenesis and drug screening for MPL syndrome. © 2018. Published by The Company of Biologists Ltd.

  6. Polymorphisms in voltage-gated sodium channel gene and susceptibility of Aedes albopictus to insecticides in three districts of northern West Bengal, India.

    Science.gov (United States)

    Chatterjee, Moytrey; Ballav, Sudeep; Maji, Ardhendu K; Basu, Nandita; Sarkar, Biplab Chandra; Saha, Pabitra

    2018-01-01

    The control and prevention of dengue largely depends on vector control measures, environmental management, and personal protection. Dengue control programmes are facing great challenges due to development of insecticide resistance among vector mosquitoes. Information on susceptibility status to different insecticides is important for national programmes to formulate vector control strategies. We have studied the larval susceptibility of Aedes albopictus to temephos and adult susceptibility to 4% DDT, 0.05% deltamethrin, and 5% malathion as per WHO protocols in the northern districts of West Bengal. Polymorphisms in the VGSC gene were studied by direct sequencing of PCR products. The Ae. albopictus larval population showed sensitive [Resistance Ratio (RR99)resistance (510) to temephos at different study sites. Adult bioassay results revealed that Ae. albopictus was highly resistant to DDT [Corrected Mortality (CM) 98%), except in Dhupguri where a low level of resistance to deltamethrin (CM = 96.25%) was recorded. None of the six important kdr mutations (S953P, I975M/V, L978, V980G, F1474C, D1703Y) were found in the VGSC of studied mosquitoes, but we identified 11 synonymous and 1 non-synonymous mutation in the VGSC gene. The higher susceptibility level to deltamethrin and malathion, along with the absence of important kdr mutations indicates that these two insecticides are still effective against Ae. albopictus in the study areas. The susceptibility status of temephos should be monitored closely as low to moderate levels of resistance were observed in few sites. A similar study is recommended for monitoring and early detection of insecticide resistance in other parts of the country.

  7. Zlib: A numerical library for optimal design of truncated power series algebra and map parameterization routines

    International Nuclear Information System (INIS)

    Yan, Y.T.

    1996-11-01

    A brief review of the Zlib development is given. Emphasized is the Zlib nerve system which uses the One-Step Index Pointers (OSIPs) for efficient computation and flexible use of the Truncated Power Series Algebra (TPSA). Also emphasized is the treatment of parameterized maps with an object-oriented language (e.g. C++). A parameterized map can be a Vector Power Series (Vps) or a Lie generator represented by an exponent of a Truncated Power Series (Tps) of which each coefficient is an object of truncated power series

  8. Measuring a truncated disk in Aquila X-1

    DEFF Research Database (Denmark)

    King, Ashley L.; Tomsick, John A.; Miller, Jon M.

    2016-01-01

    We present NuSTAR and Swift observations of the neutron star Aquila X-1 during the peak of its 2014 July outburst. The spectrum is soft with strong evidence for a broad Fe Kα line. Modeled with a relativistically broadened reflection model, we find that the inner disk is truncated with an inner r...

  9. Three novel and the common Arg677Ter RP1 protein truncating mutations causing autosomal dominant retinitis pigmentosa in a Spanish population

    Directory of Open Access Journals (Sweden)

    Antiñolo Guillermo

    2006-04-01

    Full Text Available Abstract Background Retinitis pigmentosa (RP, a clinically and genetically heterogeneous group of retinal degeneration disorders affecting the photoreceptor cells, is one of the leading causes of genetic blindness. Mutations in the photoreceptor-specific gene RP1 account for 3–10% of cases of autosomal dominant RP (adRP. Most of these mutations are clustered in a 500 bp region of exon 4 of RP1. Methods Denaturing gradient gel electrophoresis (DGGE analysis and direct genomic sequencing were used to evaluate the 5' coding region of exon 4 of the RP1 gene for mutations in 150 unrelated index adRP patients. Ophthalmic and electrophysiological examination of RP patients and relatives according to pre-existing protocols were carried out. Results Three novel disease-causing mutations in RP1 were detected: Q686X, K705fsX712 and K722fsX737, predicting truncated proteins. One novel missense mutation, Thr752Met, was detected in one family but the mutation does not co-segregate in the family, thereby excluding this amino acid variation in the protein as a cause of the disease. We found the Arg677Ter mutation, previously reported in other populations, in two independent families, confirming that this mutation is also present in a Spanish population. Conclusion Most of the mutations reported in the RP1 gene associated with adRP are expected to encode mutant truncated proteins that are approximately one third or half of the size of wild type protein. Patients with mutations in RP1 showed mild RP with variability in phenotype severity. We also observed several cases of non-penetrant mutations.

  10. Causal analysis of ordinal treatments and binary outcomes under truncation by death.

    Science.gov (United States)

    Wang, Linbo; Richardson, Thomas S; Zhou, Xiao-Hua

    2017-06-01

    It is common that in multi-arm randomized trials, the outcome of interest is "truncated by death," meaning that it is only observed or well-defined conditioning on an intermediate outcome. In this case, in addition to pairwise contrasts, the joint inference for all treatment arms is also of interest. Under a monotonicity assumption we present methods for both pairwise and joint causal analyses of ordinal treatments and binary outcomes in presence of truncation by death. We illustrate via examples the appropriateness of our assumptions in different scientific contexts.

  11. Functional analysis of truncated and site-directed mutagenesis dextransucrases to produce different type dextrans.

    Science.gov (United States)

    Wang, Chao; Zhang, Hong-Bin; Li, Meng-Qi; Hu, Xue-Qin; Li, Yao

    2017-07-01

    Dextrans with distinct molecular size and structure are increasingly being used in the food and pharmaceutical industries. Dextran is produced by dextransucrase (DSR, EC2.4.5.1), which is produced by Leuconostoc mesenteroides. DSR belongs to glycosyl hydrolase family (GH70) and synthesizes branched α-glucan (dextran) with both 5% α(1-3) and 95% α(1-6) glycosidic linkages. The DSR gene dex-YG (Genebank, Accession No. DQ345760) was cloned from the wild strain Leuconostoc mesenteroides 0326. This study generated a series of C-terminally truncated variants of dextransucrase and substituting the amino-acid residues in the active site of DSR. With shorter length of DSR, its polysaccharide-synthesizing capability was impaired heavily, whereas oligosaccharide (acting as prebiotics)-synthesizing capability increased significantly, efficiently producing special sizes of dextran. All truncated mutant enzymes were active. Results demonstrated that the catalytic domain dextransucrase was likely in 800 aa or less. Based on the three-dimensional structure model of dextransucrase built through homology modeling methods, the DSR and its mutants with the acceptor substrate of maltose and donor substrate of sucrose were studied by molecular-docking method. Substituting these amino-acid residues significantly affected enzyme activities. Compared with the wild-type dextran, mutant enzymes catalyzed the synthesis of a-glucan with 1-9% α(1-3) and 90-98% α(1-6) branching linkages. Some mutants introduced a small amount of α(1-4) linkages and α(1-2) linkages. This strategy can be effectively used for the rational protein design of dextransucrase. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Truncatable bootstrap equations in algebraic form and critical surface exponents

    Energy Technology Data Exchange (ETDEWEB)

    Gliozzi, Ferdinando [Dipartimento di Fisica, Università di Torino andIstituto Nazionale di Fisica Nucleare - sezione di Torino,Via P. Giuria 1, Torino, I-10125 (Italy)

    2016-10-10

    We describe examples of drastic truncations of conformal bootstrap equations encoding much more information than that obtained by a direct numerical approach. A three-term truncation of the four point function of a free scalar in any space dimensions provides algebraic identities among conformal block derivatives which generate the exact spectrum of the infinitely many primary operators contributing to it. In boundary conformal field theories, we point out that the appearance of free parameters in the solutions of bootstrap equations is not an artifact of truncations, rather it reflects a physical property of permeable conformal interfaces which are described by the same equations. Surface transitions correspond to isolated points in the parameter space. We are able to locate them in the case of 3d Ising model, thanks to a useful algebraic form of 3d boundary bootstrap equations. It turns out that the low-lying spectra of the surface operators in the ordinary and the special transitions of 3d Ising model form two different solutions of the same polynomial equation. Their interplay yields an estimate of the surface renormalization group exponents, y{sub h}=0.72558(18) for the ordinary universality class and y{sub h}=1.646(2) for the special universality class, which compare well with the most recent Monte Carlo calculations. Estimates of other surface exponents as well as OPE coefficients are also obtained.

  13. The truncated Wigner method for Bose-condensed gases: limits of validity and applications

    International Nuclear Information System (INIS)

    Sinatra, Alice; Lobo, Carlos; Castin, Yvan

    2002-01-01

    We study the truncated Wigner method applied to a weakly interacting spinless Bose-condensed gas which is perturbed away from thermal equilibrium by a time-dependent external potential. The principle of the method is to generate an ensemble of classical fields ψ(r) which samples the Wigner quasi-distribution function of the initial thermal equilibrium density operator of the gas, and then to evolve each classical field with the Gross-Pitaevskii equation. In the first part of the paper we improve the sampling technique over our previous work (Sinatra et al 2000 J. Mod. Opt. 47 2629-44) and we test its accuracy against the exactly solvable model of the ideal Bose gas. In the second part of the paper we investigate the conditions of validity of the truncated Wigner method. For short evolution times it is known that the time-dependent Bogoliubov approximation is valid for almost pure condensates. The requirement that the truncated Wigner method reproduces the Bogoliubov prediction leads to the constraint that the number of field modes in the Wigner simulation must be smaller than the number of particles in the gas. For longer evolution times the nonlinear dynamics of the noncondensed modes of the field plays an important role. To demonstrate this we analyse the case of a three-dimensional spatially homogeneous Bose-condensed gas and we test the ability of the truncated Wigner method to correctly reproduce the Beliaev-Landau damping of an excitation of the condensate. We have identified the mechanism which limits the validity of the truncated Wigner method: the initial ensemble of classical fields, driven by the time-dependent Gross-Pitaevskii equation, thermalizes to a classical field distribution at a temperature T class which is larger than the initial temperature T of the quantum gas. When T class significantly exceeds T a spurious damping is observed in the Wigner simulation. This leads to the second validity condition for the truncated Wigner method, T class - T

  14. six novel mutations in the TSC1 and TSC2 genes

    Indian Academy of Sciences (India)

    M. GLUSHKOVA

    2018-04-30

    Apr 30, 2018 ... RESEARCH ARTICLE ... nant disorder caused by inactivating TSC1 or TSC2 gene variants (Van ... premature protein truncation, while missense mutations are rare ..... TSC2 variants in our cohort are missense, frame-shift.

  15. A SUZAKU OBSERVATION OF NGC 4593: ILLUMINATING THE TRUNCATED DISK

    International Nuclear Information System (INIS)

    Markowitz, A. G.; Reeves, J. N.

    2009-01-01

    We report results from a 2007 Suzaku observation of the Seyfert 1 AGN NGC 4593. The narrow Fe Kα emission line has a FWHM width ∼ 4000 km s -1 , indicating emission from ∼> 5000 R g . There is no evidence for a relativistically broadened Fe K line, consistent with the presence of a radiatively efficient outer disk which is truncated or transitions to an interior radiatively inefficient flow. The Suzaku observation caught the source in a low-flux state; comparison to a 2002 XMM-Newton observation indicates that the hard X-ray flux decreased by 3.6, while the Fe Kα line intensity and width σ each roughly halved. Two model-dependent explanations for the changes in Fe Kα line profile are explored. In one, the Fe Kα line width has decreased from ∼10,000 to ∼4000 km s -1 from 2002 to 2007, suggesting that the thin disk truncation/transition radius has increased from 1000-2000 to ∼>5000 R g . However, there are indications from other compact accreting systems that such truncation radii tend to be associated only with accretion rates relative to Eddington much lower than that of NGC 4593. In the second model, the line profile in the XMM-Newton observation consists of a time-invariant narrow component plus a broad component originating from the inner part of the truncated disk (∼300 R g ) which has responded to the drop in continuum flux. The Compton reflection component strength R is ∼ 1.1, consistent with the measured Fe Kα line total equivalent width with an Fe abundance 1.7 times the solar value. The modest soft excess, modeled well by either thermal bremsstrahlung emission or by Comptonization of soft seed photons in an optical thin plasma, has fallen by a factor of ∼20 from 2002 to 2007, ruling out emission from a region 5 lt-yr in size.

  16. Observation of the dispersion of wedge waves propagating along cylinder wedge with different truncations by laser ultrasound technique

    Science.gov (United States)

    Jia, Jing; Zhang, Yu; Han, Qingbang; Jing, Xueping

    2017-10-01

    The research focuses on study the influence of truncations on the dispersion of wedge waves propagating along cylinder wedge with different truncations by using the laser ultrasound technique. The wedge waveguide models with different truncations were built by using finite element method (FEM). The dispersion curves were obtained by using 2D Fourier transformation method. Multiple mode wedge waves were observed, which was well agreed with the results estimated from Lagasse's empirical formula. We established cylinder wedge with radius of 3mm, 20° and 60°angle, with 0μm, 5μm, 10μm, 20μm, 30μm, 40μm, and 50μm truncations, respectively. It was found that non-ideal wedge tip caused abnormal dispersion of the mode of cylinder wedge, the modes of 20° cylinder wedge presents the characteristics of guide waves which propagating along hollow cylinder as the truncation increasing. Meanwhile, the modes of 60° cylinder wedge with truncations appears the characteristics of guide waves propagating along hollow cylinder, and its mode are observed clearly. The study can be used to evaluate and detect wedge structure.

  17. Truncation artifact suppression in cone-beam radionuclide transmission CT using maximum likelihood techniques: evaluation with human subjects

    International Nuclear Information System (INIS)

    Manglos, S.H.

    1992-01-01

    Transverse image truncation can be a serious problem for human imaging using cone-beam transmission CT (CB-CT) implemented on a conventional rotating gamma camera. This paper presents a reconstruction method to reduce or eliminate the artifacts resulting from the truncation. The method uses a previously published transmission maximum likelihood EM algorithm, adapted to the cone-beam geometry. The reconstruction method is evaluated qualitatively using three human subjects of various dimensions and various degrees of truncation. (author)

  18. Minimum decoding trellis length and truncation depth of wrap-around Viterbi algorithm for TBCC in mobile WiMAX

    Directory of Open Access Journals (Sweden)

    Liu Yu-Sun

    2011-01-01

    Full Text Available Abstract The performance of the wrap-around Viterbi decoding algorithm with finite truncation depth and fixed decoding trellis length is investigated for tail-biting convolutional codes in the mobile WiMAX standard. Upper bounds on the error probabilities induced by finite truncation depth and the uncertainty of the initial state are derived for the AWGN channel. The truncation depth and the decoding trellis length that yield negligible performance loss are obtained for all transmission rates over the Rayleigh channel using computer simulations. The results show that the circular decoding algorithm with an appropriately chosen truncation depth and a decoding trellis just a fraction longer than the original received code words can achieve almost the same performance as the optimal maximum likelihood decoding algorithm in mobile WiMAX. A rule of thumb for the values of the truncation depth and the trellis tail length is also proposed.

  19. On the Truncated Pareto Distribution with applications

    OpenAIRE

    Zaninetti, Lorenzo; Ferraro, Mario

    2008-01-01

    The Pareto probability distribution is widely applied in different fields such us finance, physics, hydrology, geology and astronomy. This note deals with an application of the Pareto distribution to astrophysics and more precisely to the statistical analysis of mass of stars and of diameters of asteroids. In particular a comparison between the usual Pareto distribution and its truncated version is presented. Finally a possible physical mechanism that produces Pareto tails for the distributio...

  20. On the propagation of truncated localized waves in dispersive silica

    KAUST Repository

    Salem, Mohamed; Bagci, Hakan

    2010-01-01

    Propagation characteristics of truncated Localized Waves propagating in dispersive silica and free space are numerically analyzed. It is shown that those characteristics are affected by the changes in the relation between the transverse spatial

  1. Targeted molecular profiling of rare genetic alterations in colorectal cancer using next-generation sequencing.

    Science.gov (United States)

    Jauhri, Mayank; Bhatnagar, Akanksha; Gupta, Satish; Shokeen, Yogender; Minhas, Sachin; Aggarwal, Shyam

    2016-10-01

    Mutation frequencies of common genetic alterations in colorectal cancer have been in the spotlight for many years. This study highlights few rare somatic mutations, which possess the attributes of a potential CRC biomarker yet are often neglected. Next-generation sequencing was performed over 112 tumor samples to detect genetic alterations in 31 rare genes in colorectal cancer. Mutations were detected in 26/31 (83.9 %) uncommon genes, which together contributed toward 149 gene mutations in 67/112 (59.8 %) colorectal cancer patients. The most frequent mutations include KDR (19.6 %), PTEN (17 %), FBXW7 (10.7 %), SMAD4 (10.7 %), VHL (8 %), KIT (8 %), MET (7.1 %), ATM (6.3 %), CTNNB1 (4.5 %) and CDKN2A (4.5 %). RB1, ERBB4 and ERBB2 mutations were persistent in 3.6 % patients. GNAS, FGFR2 and FGFR3 mutations were persistent in 1.8 % patients. Ten genes (EGFR, NOTCH1, SMARCB1, ABL1, STK11, SMO, RET, GNAQ, CSF1R and FLT3) were found mutated in 0.9 % patients. Lastly, no mutations were observed in AKT, HRAS, MAP2K1, PDGFR and JAK2. Significant associations were observed between VHL with tumor site, ERBB4 and SMARCB1 with tumor invasion, CTNNB1 with lack of lymph node involvement and CTNNB1, FGFR2 and FGFR3 with TNM stage. Significantly coinciding mutation pairs include PTEN and SMAD4, PTEN and KDR, EGFR and RET, EGFR and RB1, FBXW7 and CTNNB1, KDR and FGFR2, FLT3 and CTNNB1, RET and RB1, ATM and SMAD4, ATM and CDKN2A, ERBB4 and SMARCB1. This study elucidates few potential colorectal cancer biomarkers, specifically KDR, PTEN, FBXW7 and SMAD4, which are found mutated in more than 10 % patients.

  2. Three novel and two known androgen receptor gene mutations ...

    Indian Academy of Sciences (India)

    gene mutations associated with androgen insensitivity syndrome in sex-reversed XY female patients. J. Genet. ... signal and a C-terminal. Keywords. androgen insensitivity syndrome; androgen receptor; truncation mutation; N-terminal domain; XY sex reversal. .... and an increased risk of gonadal tumour. Mutations in SRY.

  3. Digestion proteomics: tracking lactoferrin truncation and peptide release during simulated gastric digestion.

    Science.gov (United States)

    Grosvenor, Anita J; Haigh, Brendan J; Dyer, Jolon M

    2014-11-01

    The extent to which nutritional and functional benefit is derived from proteins in food is related to its breakdown and digestion in the body after consumption. Further, detailed information about food protein truncation during digestion is critical to understanding and optimising the availability of bioactives, in controlling and limiting allergen release, and in minimising or monitoring the effects of processing and food preparation. However, tracking the complex array of products formed during the digestion of proteins is not easily accomplished using classical proteomics. We here present and develop a novel proteomic approach using isobaric labelling to mapping and tracking protein truncation and peptide release during simulated gastric digestion, using bovine lactoferrin as a model food protein. The relative abundance of related peptides was tracked throughout a digestion time course, and the effect of pasteurisation on peptide release assessed. The new approach to food digestion proteomics developed here therefore appears to be highly suitable not only for tracking the truncation and relative abundance of released peptides during gastric digestion, but also for determining the effects of protein modification on digestibility and potential bioavailability.

  4. Theoretical analysis of balanced truncation for linear switched systems

    DEFF Research Database (Denmark)

    Petreczky, Mihaly; Wisniewski, Rafal; Leth, John-Josef

    2012-01-01

    In this paper we present theoretical analysis of model reduction of linear switched systems based on balanced truncation, presented in [1,2]. More precisely, (1) we provide a bound on the estimation error using L2 gain, (2) we provide a system theoretic interpretation of grammians and their singu......In this paper we present theoretical analysis of model reduction of linear switched systems based on balanced truncation, presented in [1,2]. More precisely, (1) we provide a bound on the estimation error using L2 gain, (2) we provide a system theoretic interpretation of grammians...... for showing this independence is realization theory of linear switched systems. [1] H. R. Shaker and R. Wisniewski, "Generalized gramian framework for model/controller order reduction of switched systems", International Journal of Systems Science, Vol. 42, Issue 8, 2011, 1277-1291. [2] H. R. Shaker and R....... Wisniewski, "Switched Systems Reduction Framework Based on Convex Combination of Generalized Gramians", Journal of Control Science and Engineering, 2009....

  5. Propagation of coherently combined truncated laser beam arrays with beam distortions in non-Kolmogorov turbulence.

    Science.gov (United States)

    Tao, Rumao; Si, Lei; Ma, Yanxing; Zhou, Pu; Liu, Zejin

    2012-08-10

    The propagation properties of coherently combined truncated laser beam arrays with beam distortions through non-Kolmogorov turbulence are studied in detail both analytically and numerically. The analytical expressions for the average intensity and the beam width of coherently combined truncated laser beam arrays with beam distortions propagating through turbulence are derived based on the combination of statistical optics methods and the extended Huygens-Fresnel principle. The effect of beam distortions, such as amplitude modulation and phase fluctuation, is studied by numerical examples. The numerical results reveal that phase fluctuations have significant influence on the spreading of coherently combined truncated laser beam arrays in non-Kolmogorov turbulence, and the effects of the phase fluctuations can be negligible as long as the phase fluctuations are controlled under a certain level, i.e., a>0.05 for the situation considered in the paper. Furthermore, large phase fluctuations can convert the beam distribution rapidly to a Gaussian form, vary the spreading, weaken the optimum truncation effects, and suppress the dependence of spreading on the parameters of the non-Kolmogorov turbulence.

  6. Solving Schwinger-Dyson equations by truncation in zero-dimensional scalar quantum field theory

    International Nuclear Information System (INIS)

    Okopinska, A.

    1991-01-01

    Three sets of Schwinger-Dyson equations, for all Green's functions, for connected Green's functions, and for proper vertices, are considered in scalar quantum field theory. A truncation scheme applied to the three sets gives three different approximation series for Green's functions. For the theory in zero-dimensional space-time the results for respective two-point Green's functions are compared with the exact value calculated numerically. The best convergence of the truncation scheme is obtained for the case of proper vertices

  7. Fitting Social Network Models Using Varying Truncation Stochastic Approximation MCMC Algorithm

    KAUST Repository

    Jin, Ick Hoon

    2013-10-01

    The exponential random graph model (ERGM) plays a major role in social network analysis. However, parameter estimation for the ERGM is a hard problem due to the intractability of its normalizing constant and the model degeneracy. The existing algorithms, such as Monte Carlo maximum likelihood estimation (MCMLE) and stochastic approximation, often fail for this problem in the presence of model degeneracy. In this article, we introduce the varying truncation stochastic approximation Markov chain Monte Carlo (SAMCMC) algorithm to tackle this problem. The varying truncation mechanism enables the algorithm to choose an appropriate starting point and an appropriate gain factor sequence, and thus to produce a reasonable parameter estimate for the ERGM even in the presence of model degeneracy. The numerical results indicate that the varying truncation SAMCMC algorithm can significantly outperform the MCMLE and stochastic approximation algorithms: for degenerate ERGMs, MCMLE and stochastic approximation often fail to produce any reasonable parameter estimates, while SAMCMC can do; for nondegenerate ERGMs, SAMCMC can work as well as or better than MCMLE and stochastic approximation. The data and source codes used for this article are available online as supplementary materials. © 2013 American Statistical Association, Institute of Mathematical Statistics, and Interface Foundation of North America.

  8. Consensus strategy in genes prioritization and combined bioinformatics analysis for preeclampsia pathogenesis.

    Science.gov (United States)

    Tejera, Eduardo; Cruz-Monteagudo, Maykel; Burgos, Germán; Sánchez, María-Eugenia; Sánchez-Rodríguez, Aminael; Pérez-Castillo, Yunierkis; Borges, Fernanda; Cordeiro, Maria Natália Dias Soeiro; Paz-Y-Miño, César; Rebelo, Irene

    2017-08-08

    Preeclampsia is a multifactorial disease with unknown pathogenesis. Even when recent studies explored this disease using several bioinformatics tools, the main objective was not directed to pathogenesis. Additionally, consensus prioritization was proved to be highly efficient in the recognition of genes-disease association. However, not information is available about the consensus ability to early recognize genes directly involved in pathogenesis. Therefore our aim in this study is to apply several theoretical approaches to explore preeclampsia; specifically those genes directly involved in the pathogenesis. We firstly evaluated the consensus between 12 prioritization strategies to early recognize pathogenic genes related to preeclampsia. A communality analysis in the protein-protein interaction network of previously selected genes was done including further enrichment analysis. The enrichment analysis includes metabolic pathways as well as gene ontology. Microarray data was also collected and used in order to confirm our results or as a strategy to weight the previously enriched pathways. The consensus prioritized gene list was rationally filtered to 476 genes using several criteria. The communality analysis showed an enrichment of communities connected with VEGF-signaling pathway. This pathway is also enriched considering the microarray data. Our result point to VEGF, FLT1 and KDR as relevant pathogenic genes, as well as those connected with NO metabolism. Our results revealed that consensus strategy improve the detection and initial enrichment of pathogenic genes, at least in preeclampsia condition. Moreover the combination of the first percent of the prioritized genes with protein-protein interaction network followed by communality analysis reduces the gene space. This approach actually identifies well known genes related with pathogenesis. However, genes like HSP90, PAK2, CD247 and others included in the first 1% of the prioritized list need to be further

  9. Evolution Analysis of the Aux/IAA Gene Family in Plants Shows Dual Origins and Variable Nuclear Localization Signals

    Directory of Open Access Journals (Sweden)

    Wentao Wu

    2017-10-01

    Full Text Available The plant hormone auxin plays pivotal roles in many aspects of plant growth and development. The auxin/indole-3-acetic acid (Aux/IAA gene family encodes short-lived nuclear proteins acting on auxin perception and signaling, but the evolutionary history of this gene family remains to be elucidated. In this study, the Aux/IAA gene family in 17 plant species covering all major lineages of plants is identified and analyzed by using multiple bioinformatics methods. A total of 434 Aux/IAA genes was found among these plant species, and the gene copy number ranges from three (Physcomitrella patens to 63 (Glycine max. The phylogenetic analysis shows that the canonical Aux/IAA proteins can be generally divided into five major clades, and the origin of Aux/IAA proteins could be traced back to the common ancestor of land plants and green algae. Many truncated Aux/IAA proteins were found, and some of these truncated Aux/IAA proteins may be generated from the C-terminal truncation of auxin response factor (ARF proteins. Our results indicate that tandem and segmental duplications play dominant roles for the expansion of the Aux/IAA gene family mainly under purifying selection. The putative nuclear localization signals (NLSs in Aux/IAA proteins are conservative, and two kinds of new primordial bipartite NLSs in P. patens and Selaginella moellendorffii were discovered. Our findings not only give insights into the origin and expansion of the Aux/IAA gene family, but also provide a basis for understanding their functions during the course of evolution.

  10. Evolution Analysis of the Aux/IAA Gene Family in Plants Shows Dual Origins and Variable Nuclear Localization Signals.

    Science.gov (United States)

    Wu, Wentao; Liu, Yaxue; Wang, Yuqian; Li, Huimin; Liu, Jiaxi; Tan, Jiaxin; He, Jiadai; Bai, Jingwen; Ma, Haoli

    2017-10-08

    The plant hormone auxin plays pivotal roles in many aspects of plant growth and development. The auxin/indole-3-acetic acid (Aux/IAA) gene family encodes short-lived nuclear proteins acting on auxin perception and signaling, but the evolutionary history of this gene family remains to be elucidated. In this study, the Aux/IAA gene family in 17 plant species covering all major lineages of plants is identified and analyzed by using multiple bioinformatics methods. A total of 434 Aux/IAA genes was found among these plant species, and the gene copy number ranges from three ( Physcomitrella patens ) to 63 ( Glycine max ). The phylogenetic analysis shows that the canonical Aux/IAA proteins can be generally divided into five major clades, and the origin of Aux/IAA proteins could be traced back to the common ancestor of land plants and green algae. Many truncated Aux/IAA proteins were found, and some of these truncated Aux/IAA proteins may be generated from the C-terminal truncation of auxin response factor (ARF) proteins. Our results indicate that tandem and segmental duplications play dominant roles for the expansion of the Aux/IAA gene family mainly under purifying selection. The putative nuclear localization signals (NLSs) in Aux/IAA proteins are conservative, and two kinds of new primordial bipartite NLSs in P. patens and Selaginella moellendorffii were discovered. Our findings not only give insights into the origin and expansion of the Aux/IAA gene family, but also provide a basis for understanding their functions during the course of evolution.

  11. Reduction of Truncation Errors in Planar Near-Field Aperture Antenna Measurements Using the Gerchberg-Papoulis Algorithm

    DEFF Research Database (Denmark)

    Martini, Enrica; Breinbjerg, Olav; Maci, Stefano

    2008-01-01

    A simple and effective procedure for the reduction of truncation errors in planar near-field measurements of aperture antennas is presented. The procedure relies on the consideration that, due to the scan plane truncation, the calculated plane wave spectrum of the field radiated by the antenna is...

  12. Optimal auxiliary Hamiltonians for truncated boson-space calculations by means of a maximal-decoupling variational principle

    International Nuclear Information System (INIS)

    Li, C.

    1991-01-01

    A new method based on a maximal-decoupling variational principle is proposed to treat the Pauli-principle constraints for calculations of nuclear collective motion in a truncated boson space. The viability of the method is demonstrated through an application to the multipole form of boson Hamiltonians for the single-j and nondegenerate multi-j pairing interactions. While these boson Hamiltonians are Hermitian and contain only one- and two-boson terms, they are also the worst case for truncated boson-space calculations because they are not amenable to any boson truncations at all. By using auxiliary Hamiltonians optimally determined by the maximal-decoupling variational principle, however, truncations in the boson space become feasible and even yield reasonably accurate results. The method proposed here may thus be useful for doing realistic calculations of nuclear collective motion as well as for obtaining a viable interacting-boson-model type of boson Hamiltonian from the shell model

  13. Phase retrieval via incremental truncated amplitude flow algorithm

    Science.gov (United States)

    Zhang, Quanbing; Wang, Zhifa; Wang, Linjie; Cheng, Shichao

    2017-10-01

    This paper considers the phase retrieval problem of recovering the unknown signal from the given quadratic measurements. A phase retrieval algorithm based on Incremental Truncated Amplitude Flow (ITAF) which combines the ITWF algorithm and the TAF algorithm is proposed. The proposed ITAF algorithm enhances the initialization by performing both of the truncation methods used in ITWF and TAF respectively, and improves the performance in the gradient stage by applying the incremental method proposed in ITWF to the loop stage of TAF. Moreover, the original sampling vector and measurements are preprocessed before initialization according to the variance of the sensing matrix. Simulation experiments verified the feasibility and validity of the proposed ITAF algorithm. The experimental results show that it can obtain higher success rate and faster convergence speed compared with other algorithms. Especially, for the noiseless random Gaussian signals, ITAF can recover any real-valued signal accurately from the magnitude measurements whose number is about 2.5 times of the signal length, which is close to the theoretic limit (about 2 times of the signal length). And it usually converges to the optimal solution within 20 iterations which is much less than the state-of-the-art algorithms.

  14. Learning Mixtures of Truncated Basis Functions from Data

    DEFF Research Database (Denmark)

    Langseth, Helge; Nielsen, Thomas Dyhre; Pérez-Bernabé, Inmaculada

    2014-01-01

    In this paper we investigate methods for learning hybrid Bayesian networks from data. First we utilize a kernel density estimate of the data in order to translate the data into a mixture of truncated basis functions (MoTBF) representation using a convex optimization technique. When utilizing a ke...... propose an alternative learning method that relies on the cumulative distribution function of the data. Empirical results demonstrate the usefulness of the approaches: Even though the methods produce estimators that are slightly poorer than the state of the art (in terms of log......In this paper we investigate methods for learning hybrid Bayesian networks from data. First we utilize a kernel density estimate of the data in order to translate the data into a mixture of truncated basis functions (MoTBF) representation using a convex optimization technique. When utilizing......-likelihood), they are significantly faster, and therefore indicate that the MoTBF framework can be used for inference and learning in reasonably sized domains. Furthermore, we show how a particular sub- class of MoTBF potentials (learnable by the proposed methods) can be exploited to significantly reduce complexity during inference....

  15. Determination of αS from scaling violations of truncated moments of structure functions

    International Nuclear Information System (INIS)

    Forte, Stefano; Latorre, J.I.; Magnea, Lorenzo; Piccione, Andrea

    2002-01-01

    We determine the strong coupling α S (M Z ) from scaling violations of truncated moments of the nonsinglet deep inelastic structure function F 2 . Truncated moments are determined from BCDMS and NMC data using a neural network parametrization which retains the full experimental information on errors and correlations. Our method minimizes all sources of theoretical uncertainty and bias which characterize extractions of α S from scaling violations. We obtain α S (M Z )=0.124 +0.004 -0.007 (exp.) +0.003 -0.004 (th.)

  16. ESPRIT: A Method for Defining Soluble Expression Constructs in Poorly Understood Gene Sequences.

    Science.gov (United States)

    Mas, Philippe J; Hart, Darren J

    2017-01-01

    Production of soluble, purifiable domains or multi-domain fragments of proteins is a prerequisite for structural biology and other applications. When target sequences are poorly annotated, or when there are few similar sequences available for alignments, identification of domains can be problematic. A method called expression of soluble proteins by random incremental truncation (ESPRIT) addresses this problem by high-throughput automated screening of tens of thousands of enzymatically truncated gene fragments. Rare soluble constructs are identified by experimental screening, and the boundaries revealed by DNA sequencing.

  17. The prevalence of CHD7 missense versus truncating mutations is higher in patients with Kallmann syndrome than in typical CHARGE patients

    DEFF Research Database (Denmark)

    Marcos, Séverine; Sarfati, Julie; Leroy, Chrystel

    2014-01-01

    CONTEXT: Mutations in CHD7, a gene previously implicated in CHARGE (coloboma, heart defect, choanal atresia, retardation of growth and/or development, genital hypoplasia, ear anomalies) syndrome, have been reported in patients presenting with Kallmann syndrome (KS) or congenital hypogonadotropic...... hypogonadism (CHH). Most mutations causing CHARGE syndrome result in premature stop codons and occur de novo, but the proportion of truncating vs nontruncating mutations in KS and CHH patients is still unknown. OBJECTIVE: The objective of the study was to determine the nature, prevalence, mode of transmission......, and clinical spectrum of CHD7 mutations in a large series of patients. DESIGN: We studied 209 KS and 94 CHH patients. These patients had not been diagnosed with CHARGE syndrome according to the current criteria. We searched for mutations in 16 KS and CHH genes including CHD7. RESULTS: We found presumably...

  18. Sodium Channel Mutations and Pyrethroid Resistance in Aedes aegypti

    Directory of Open Access Journals (Sweden)

    Yuzhe Du

    2016-10-01

    Full Text Available Pyrethroid insecticides are widely used to control insect pests and human disease vectors. Voltage-gated sodium channels are the primary targets of pyrethroid insecticides. Mutations in the sodium channel have been shown to be responsible for pyrethroid resistance, known as knockdown resistance (kdr, in various insects including mosquitoes. In Aedes aegypti mosquitoes, the principal urban vectors of dengue, zika, and yellow fever viruses, multiple single nucleotide polymorphisms in the sodium channel gene have been found in pyrethroid-resistant populations and some of them have been functionally confirmed to be responsible for kdr in an in vitro expression system, Xenopus oocytes. This mini-review aims to provide an update on the identification and functional characterization of pyrethroid resistance-associated sodium channel mutations from Aedes aegypti. The collection of kdr mutations not only helped us develop molecular markers for resistance monitoring, but also provided valuable information for computational molecular modeling of pyrethroid receptor sites on the sodium channel.

  19. Performance Comparison of Assorted Color Spaces for Multilevel Block Truncation Coding based Face Recognition

    OpenAIRE

    H.B. Kekre; Sudeep Thepade; Karan Dhamejani; Sanchit Khandelwal; Adnan Azmi

    2012-01-01

    The paper presents a performance analysis of Multilevel Block Truncation Coding based Face Recognition among widely used color spaces. In [1], Multilevel Block Truncation Coding was applied on the RGB color space up to four levels for face recognition. Better results were obtained when the proposed technique was implemented using Kekre’s LUV (K’LUV) color space [25]. This was the motivation to test the proposed technique using assorted color spaces. For experimental analysis, two face databas...

  20. The evidence for synthesis of truncated triangular silver nanoplates in the presence of CTAB

    International Nuclear Information System (INIS)

    He Xin; Zhao Xiujian; Chen Yunxia; Feng Jinyang

    2008-01-01

    Truncated triangular silver nanoplates were prepared by a solution-phase approach, which involved the seed-mediated growth of silver nanoparticles in the presence of cetyltrimethylammonium bromide (CTAB) at 40 deg. C. The result of X-ray diffraction indicates that the as-prepared nanoparticles are made of pure face centered cubic silver. Transmission electron microscopy and atomic force microscopy studies show that the truncated triangular silver nanoplates, with edge lengths of 50 ± 5 nm and thicknesses of 27 ± 3 nm, are oriented differently on substrates of a copper grid and a fresh mica flake. The corners of these nanoplates are round. The selected area electron diffraction analysis reveals that the silver nanoplates are single crystals with an atomically flat surface. We determine the holistic morphology of truncated triangular silver nanoplates through the above measurements with the aid of computer-aided 3D perspective images

  1. Cross-layer combining of power control and adaptive modulation with truncated ARQ for cognitive radios

    Institute of Scientific and Technical Information of China (English)

    CHENG Shi-lun; YANG Zhen

    2008-01-01

    To maximize throughput and to satisfy users' requirements in cognitive radios, a cross-layer optimization problem combining adaptive modulation and power control at the physical layer and truncated automatic repeat request at the medium access control layer is proposed. Simulation results show the combination of power control, adaptive modulation, and truncated automatic repeat request can regulate transmitter powers and increase the total throughput effectively.

  2. Epitope-positive truncating MLH1 mutation and loss of PMS2: implications for IHC-directed genetic testing for Lynch syndrome.

    Science.gov (United States)

    Zighelboim, Israel; Powell, Matthew A; Babb, Sheri A; Whelan, Alison J; Schmidt, Amy P; Clendenning, Mark; Senter, Leigha; Thibodeau, Stephen N; de la Chapelle, Albert; Goodfellow, Paul J

    2009-01-01

    We assessed mismatch repair by immunohistochemistry (IHC) and microsatellite instability (MSI) analysis in an early onset endometrial cancer and a sister's colon cancer. We demonstrated high-level MSI and normal expression for MLH1, MSH2 and MSH6. PMS2 failed to stain in both tumors, strongly implicating a PMS2 defect. This family did not meet clinical criteria for Lynch syndrome. However, early onset endometrial cancers in the proband and her sister, a metachronous colorectal cancer in the sister as well as MSI in endometrial and colonic tumors suggested a heritable mismatch repair defect. PCR-based direct exonic sequencing and multiplex ligation-dependent probe amplification (MLPA) were undertaken to search for PMS2 mutations in the germline DNA from the proband and her sister. No mutation was identified in the PMS2 gene. However, PMS2 exons 3, 4, 13, 14, 15 were not evaluated by MLPA and as such, rearrangements involving those exons cannot be excluded. Clinical testing for MLH1 and MSH2 mutation revealed a germline deletion of MLH1 exons 14 and 15. This MLH1 germline deletion leads to an immunodetectable stable C-terminal truncated MLH1 protein which based on the IHC staining must abrogate PMS2 stabilization. To the best of our knowledge, loss of PMS2 in MLH1 truncating mutation carriers that express MLH1 in their tumors has not been previously reported. This family points to a potential limitation of IHC-directed gene testing for suspected Lynch syndrome and the need to consider comprehensive MLH1 testing for individuals whose tumors lack PMS2 but for whom PMS2 mutations are not identified.

  3. Dual scan CT image recovery from truncated projections

    Science.gov (United States)

    Sarkar, Shubhabrata; Wahi, Pankaj; Munshi, Prabhat

    2017-12-01

    There are computerized tomography (CT) scanners available commercially for imaging small objects and they are often categorized as mini-CT X-ray machines. One major limitation of these machines is their inability to scan large objects with good image quality because of the truncation of projection data. An algorithm is proposed in this work which enables such machines to scan large objects while maintaining the quality of the recovered image.

  4. Tau truncation is a productive posttranslational modification of neurofibrillary degeneration in Alzheimer's disease.

    Science.gov (United States)

    Kovacech, B; Novak, M

    2010-12-01

    Deposits of the misfolded neuronal protein tau are major hallmarks of neurodegeneration in Alzheimer's disease (AD) and other tauopathies. The etiology of the transformation process of the intrinsically disordered soluble protein tau into the insoluble misordered aggregate has attracted much attention. Tau undergoes multiple modifications in AD, most notably hyperphosphorylation and truncation. Hyperphosphorylation is widely regarded as the hottest candidate for the inducer of the neurofibrillary pathology. However, the true nature of the impetus that initiates the whole process in the human brains remains unknown. In AD, several site-specific tau cleavages were identified and became connected to the progression of the disease. In addition, western blot analyses of tau species in AD brains reveal multitudes of various truncated forms. In this review we summarize evidence showing that tau truncation alone is sufficient to induce the complete cascade of neurofibrillary pathology, including hyperphosphorylation and accumulation of misfolded insoluble forms of tau. Therefore, proteolytical abnormalities in the stressed neurons and production of aberrant tau cleavage products deserve closer attention and should be considered as early therapeutic targets for Alzheimer's disease.

  5. Parameter Estimation and Model Selection for Mixtures of Truncated Exponentials

    DEFF Research Database (Denmark)

    Langseth, Helge; Nielsen, Thomas Dyhre; Rumí, Rafael

    2010-01-01

    Bayesian networks with mixtures of truncated exponentials (MTEs) support efficient inference algorithms and provide a flexible way of modeling hybrid domains (domains containing both discrete and continuous variables). On the other hand, estimating an MTE from data has turned out to be a difficul...

  6. Amplitude of Light Scattering by a Truncated Pyramid and Cone in the Rayleigh-Gans-Debye Approximation

    Directory of Open Access Journals (Sweden)

    Konstantin A. Shapovalov

    2013-01-01

    Full Text Available The article considers general approach to structured particle and particle system form factor calculation in the Rayleigh-Gans-Debye (RGD approximation. Using this approach, amplitude of light scattering by a truncated pyramid and cone formulas in RGD approximation are obtained. Light scattering indicator by a truncated pyramid and cone in the RGD approximation are calculated.

  7. Protoplanetary disc truncation mechanisms in stellar clusters: comparing external photoevaporation and tidal encounters

    Science.gov (United States)

    Winter, A. J.; Clarke, C. J.; Rosotti, G.; Ih, J.; Facchini, S.; Haworth, T. J.

    2018-04-01

    Most stars form and spend their early life in regions of enhanced stellar density. Therefore the evolution of protoplanetary discs (PPDs) hosted by such stars are subject to the influence of other members of the cluster. Physically, PPDs might be truncated either by photoevaporation due to ultraviolet flux from massive stars, or tidal truncation due to close stellar encounters. Here we aim to compare the two effects in real cluster environments. In this vein we first review the properties of well studied stellar clusters with a focus on stellar number density, which largely dictates the degree of tidal truncation, and far ultraviolet (FUV) flux, which is indicative of the rate of external photoevaporation. We then review the theoretical PPD truncation radius due to an arbitrary encounter, additionally taking into account the role of eccentric encounters that play a role in hot clusters with a 1D velocity dispersion σv ≳ 2 km/s. Our treatment is then applied statistically to varying local environments to establish a canonical threshold for the local stellar density (nc ≳ 104 pc-3) for which encounters can play a significant role in shaping the distribution of PPD radii over a timescale ˜3 Myr. By combining theoretical mass loss rates due to FUV flux with viscous spreading in a PPD we establish a similar threshold for which a massive disc is completely destroyed by external photoevaporation. Comparing these thresholds in local clusters we find that if either mechanism has a significant impact on the PPD population then photoevaporation is always the dominating influence.

  8. The complete mitochondrial genome sequence of the spider habronattus oregonensis reveals rearranged and extremely truncated tRNAs

    International Nuclear Information System (INIS)

    Masta, Susan E.; Boore, Jeffrey L.

    2004-01-01

    We sequenced the entire mitochondrial genome of the jumping spider Habronattus oregonensis of the arachnid order Araneae (Arthropoda: Chelicerata). A number of unusual features distinguish this genome from other chelicerate and arthropod mitochondrial genomes. Most of the transfer RNA gene sequences are greatly reduced in size and cannot be folded into typical cloverleaf-shaped secondary structures. At least nine of the tRNA sequences lack the potential to form TYC arm stem pairings, and instead are inferred to have TV-replacement loops. Furthermore, sequences that could encode the 3' aminoacyl acceptor stems in at least 10 tRNAs appear to be lacking, because fully paired acceptor stems are not possible and because the downstream sequences instead encode adjacent genes. Hence, these appear to be among the smallest known tRNA genes. We postulate that an RNA editing mechanism must exist to restore the 3' aminoacyl acceptor stems in order to allow the tRNAs to function. At least seven tRN As are rearranged with respect to the chelicerate Limulus polyphemus, although the arrangement of the protein-coding genes is identical. Most mitochondrial protein-coding genes of H. oregonensis have ATN as initiation codons, as commonly found in arthropod mtDNAs, but cytochrome oxidase subunit 2 and 3 genes apparently use UUG as an initiation codon. Finally, many of the gene sequences overlap one another and are truncated. This 14,381 bp genome, the first mitochondrial genome of a spider yet sequenced, is one of the smallest arthropod mitochondrial genomes known. We suggest that post transcriptional RNA editing can likely maintain function of the tRNAs while permitting the accumulation of mutations that would otherwise be deleterious. Such mechanisms may have allowed for the minimization of the spider mitochondrial genome

  9. Five-dimensional truncation of the plane incompressible navier-stokes equations

    Energy Technology Data Exchange (ETDEWEB)

    Boldrighini, C [Camerino Univ. (Italy). Istituto di Matematica; Franceschini, V [Modena Univ. (Italy). Istituto Matematico

    1979-01-01

    A five-modes truncation of the Navier-Stokes equations for a two dimensional incompressible fluid on a torus is considered. A computer analysis shows that for a certain range of the Reynolds number the system exhibits a stochastic behaviour, approached through an involved sequence of bifurcations.

  10. Exact method for the simulation of Coulombic systems by spherically truncated, pairwise r-1 summation

    International Nuclear Information System (INIS)

    Wolf, D.; Keblinski, P.; Phillpot, S.R.; Eggebrecht, J.

    1999-01-01

    Based on a recent result showing that the net Coulomb potential in condensed ionic systems is rather short ranged, an exact and physically transparent method permitting the evaluation of the Coulomb potential by direct summation over the r -1 Coulomb pair potential is presented. The key observation is that the problems encountered in determining the Coulomb energy by pairwise, spherically truncated r -1 summation are a direct consequence of the fact that the system summed over is practically never neutral. A simple method is developed that achieves charge neutralization wherever the r -1 pair potential is truncated. This enables the extraction of the Coulomb energy, forces, and stresses from a spherically truncated, usually charged environment in a manner that is independent of the grouping of the pair terms. The close connection of our approach with the Ewald method is demonstrated and exploited, providing an efficient method for the simulation of even highly disordered ionic systems by direct, pairwise r -1 summation with spherical truncation at rather short range, i.e., a method which fully exploits the short-ranged nature of the interactions in ionic systems. The method is validated by simulations of crystals, liquids, and interfacial systems, such as free surfaces and grain boundaries. copyright 1999 American Institute of Physics

  11. Hyperbolic Cross Truncations for Stochastic Fourier Cosine Series

    Science.gov (United States)

    Zhang, Zhihua

    2014-01-01

    Based on our decomposition of stochastic processes and our asymptotic representations of Fourier cosine coefficients, we deduce an asymptotic formula of approximation errors of hyperbolic cross truncations for bivariate stochastic Fourier cosine series. Moreover we propose a kind of Fourier cosine expansions with polynomials factors such that the corresponding Fourier cosine coefficients decay very fast. Although our research is in the setting of stochastic processes, our results are also new for deterministic functions. PMID:25147842

  12. Optical asymmetric cryptography based on elliptical polarized light linear truncation and a numerical reconstruction technique.

    Science.gov (United States)

    Lin, Chao; Shen, Xueju; Wang, Zhisong; Zhao, Cheng

    2014-06-20

    We demonstrate a novel optical asymmetric cryptosystem based on the principle of elliptical polarized light linear truncation and a numerical reconstruction technique. The device of an array of linear polarizers is introduced to achieve linear truncation on the spatially resolved elliptical polarization distribution during image encryption. This encoding process can be characterized as confusion-based optical cryptography that involves no Fourier lens and diffusion operation. Based on the Jones matrix formalism, the intensity transmittance for this truncation is deduced to perform elliptical polarized light reconstruction based on two intensity measurements. Use of a quick response code makes the proposed cryptosystem practical, with versatile key sensitivity and fault tolerance. Both simulation and preliminary experimental results that support theoretical analysis are presented. An analysis of the resistance of the proposed method on a known public key attack is also provided.

  13. The Truncated Lognormal Distribution as a Luminosity Function for SWIFT-BAT Gamma-Ray Bursts

    Directory of Open Access Journals (Sweden)

    Lorenzo Zaninetti

    2016-11-01

    Full Text Available The determination of the luminosity function (LF in Gamma ray bursts (GRBs depends on the adopted cosmology, each one characterized by its corresponding luminosity distance. Here, we analyze three cosmologies: the standard cosmology, the plasma cosmology and the pseudo-Euclidean universe. The LF of the GRBs is firstly modeled by the lognormal distribution and the four broken power law and, secondly, by a truncated lognormal distribution. The truncated lognormal distribution fits acceptably the range in luminosity of GRBs as a function of the redshift.

  14. Functional defect of truncated hepatocyte nuclear factor-1{alpha} (G554fsX556) associated with maturity-onset diabetes of the young

    Energy Technology Data Exchange (ETDEWEB)

    Kooptiwut, Suwattanee, E-mail: S_kooptiwut@hotmail.com [Department of Physiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Sujjitjoon, Jatuporn [Department of Immunology and Immunology Graduate Program, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Plengvidhya, Nattachet [Department of Immunology and Immunology Graduate Program, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Division of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Boonyasrisawat, Watip; Chongjaroen, Nalinee; Jungtrakoon, Prapapron [Department of Immunology and Immunology Graduate Program, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Semprasert, Namoiy [Department of Physiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Furuta, Hiroto; Nanjo, Kishio [The First Department, Wakayama Medical University (Japan); Banchuin, Napatawn [Department of Immunology and Immunology Graduate Program, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Yenchitsomanus, Pa-thai [Division of Medical Molecular Biology, Medicine Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Medical Biotechnology Unit, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Bangkok (Thailand)

    2009-05-22

    A novel frameshift mutation attributable to 14-nucleotide insertion in hepatocyte nuclear factor-1{alpha} (HNF-1{alpha}) encoding a truncated HNF-1{alpha} (G554fsX556) with 76-amino acid deletion at its carboxyl terminus was identified in a Thai family with maturity-onset diabetes of the young (MODY). The wild-type and mutant HNF-1{alpha} proteins were expressed by in vitro transcription and translation (TNT) assay and by transfection in HeLa cells. The wild-type and mutant HNF-1{alpha} could similarly bind to human glucose-transporter 2 (GLUT2) promoter examined by electrophoretic mobility shift assay (EMSA). However, the transactivation activities of mutant HNF-1{alpha} on human GLUT2 and rat L-type pyruvate kinase (L-PK) promoters in HeLa cells determined by luciferase reporter assay were reduced to approximately 55-60% of the wild-type protein. These results suggested that the functional defect of novel truncated HNF-1{alpha} (G554fsX556) on the transactivation of its target-gene promoters would account for the {beta}-cell dysfunction associated with the pathogenesis of MODY.

  15. Functional defect of truncated hepatocyte nuclear factor-1α (G554fsX556) associated with maturity-onset diabetes of the young

    International Nuclear Information System (INIS)

    Kooptiwut, Suwattanee; Sujjitjoon, Jatuporn; Plengvidhya, Nattachet; Boonyasrisawat, Watip; Chongjaroen, Nalinee; Jungtrakoon, Prapapron; Semprasert, Namoiy; Furuta, Hiroto; Nanjo, Kishio; Banchuin, Napatawn; Yenchitsomanus, Pa-thai

    2009-01-01

    A novel frameshift mutation attributable to 14-nucleotide insertion in hepatocyte nuclear factor-1α (HNF-1α) encoding a truncated HNF-1α (G554fsX556) with 76-amino acid deletion at its carboxyl terminus was identified in a Thai family with maturity-onset diabetes of the young (MODY). The wild-type and mutant HNF-1α proteins were expressed by in vitro transcription and translation (TNT) assay and by transfection in HeLa cells. The wild-type and mutant HNF-1α could similarly bind to human glucose-transporter 2 (GLUT2) promoter examined by electrophoretic mobility shift assay (EMSA). However, the transactivation activities of mutant HNF-1α on human GLUT2 and rat L-type pyruvate kinase (L-PK) promoters in HeLa cells determined by luciferase reporter assay were reduced to approximately 55-60% of the wild-type protein. These results suggested that the functional defect of novel truncated HNF-1α (G554fsX556) on the transactivation of its target-gene promoters would account for the β-cell dysfunction associated with the pathogenesis of MODY.

  16. Cdx and Hox genes differentially regulate posterior axial growth in mammalian embryos

    NARCIS (Netherlands)

    Young, Teddy; Rowland, Jennifer Elizabeth; van de Ven, Cesca; Bialecka, Monika; Novoa, Ana; Carapuco, Marta; van Nes, Johan; de Graaff, Wim; Duluc, Isabelle; Freund, Jean-Noël; Beck, Felix; Mallo, Moises; Deschamps, Jacqueline

    2009-01-01

    Hox and Cdx transcription factors regulate embryonic positional identities. Cdx mutant mice display posterior body truncations of the axial skeleton, neuraxis, and caudal urorectal structures. We show that trunk Hox genes stimulate axial extension, as they can largely rescue these Cdx mutant

  17. De Novo Truncating Mutations in AHDC1 in Individuals with Syndromic Expressive Language Delay, Hypotonia, and Sleep Apnea

    Science.gov (United States)

    Xia, Fan; Bainbridge, Matthew N.; Tan, Tiong Yang; Wangler, Michael F.; Scheuerle, Angela E.; Zackai, Elaine H.; Harr, Margaret H.; Sutton, V. Reid; Nalam, Roopa L.; Zhu, Wenmiao; Nash, Margot; Ryan, Monique M.; Yaplito-Lee, Joy; Hunter, Jill V.; Deardorff, Matthew A.; Penney, Samantha J.; Beaudet, Arthur L.; Plon, Sharon E.; Boerwinkle, Eric A.; Lupski, James R.; Eng, Christine M.; Muzny, Donna M.; Yang, Yaping; Gibbs, Richard A.

    2014-01-01

    Clinical whole-exome sequencing (WES) for identification of mutations leading to Mendelian disease has been offered to the medical community since 2011. Clinically undiagnosed neurological disorders are the most frequent basis for test referral, and currently, approximately 25% of such cases are diagnosed at the molecular level. To date, there are approximately 4,000 “known” disease-associated loci, and many are associated with striking dysmorphic features, making genotype-phenotype correlations relatively straightforward. A significant fraction of cases, however, lack characteristic dysmorphism or clinical pathognomonic traits and are dependent upon molecular tests for definitive diagnoses. Further, many molecular diagnoses are guided by recent gene-disease association discoveries. Hence, there is a critical interplay between clinical testing and research leading to gene-disease association discovery. Here, we describe four probands, all of whom presented with hypotonia, intellectual disability, global developmental delay, and mildly dysmorphic facial features. Three of the four also had sleep apnea. Each was a simplex case without a remarkable family history. Using WES, we identified AHDC1 de novo truncating mutations that most likely cause this genetic syndrome. PMID:24791903

  18. Generation of truncated recombinant form of tumor necrosis factor ...

    African Journals Online (AJOL)

    Purpose: To produce truncated recombinant form of tumor necrosis factor receptor 1 (TNFR1), cysteine-rich domain 2 (CRD2) and CRD3 regions of the receptor were generated using pET28a and E. coli/BL21. Methods: DNA coding sequence of CRD2 and CRD3 was cloned into pET28a vector and the corresponding ...

  19. Exact fan-beam image reconstruction algorithm for truncated projection data acquired from an asymmetric half-size detector

    International Nuclear Information System (INIS)

    Leng Shuai; Zhuang Tingliang; Nett, Brian E; Chen Guanghong

    2005-01-01

    In this paper, we present a new algorithm designed for a specific data truncation problem in fan-beam CT. We consider a scanning configuration in which the fan-beam projection data are acquired from an asymmetrically positioned half-sized detector. Namely, the asymmetric detector only covers one half of the scanning field of view. Thus, the acquired fan-beam projection data are truncated at every view angle. If an explicit data rebinning process is not invoked, this data acquisition configuration will reek havoc on many known fan-beam image reconstruction schemes including the standard filtered backprojection (FBP) algorithm and the super-short-scan FBP reconstruction algorithms. However, we demonstrate that a recently developed fan-beam image reconstruction algorithm which reconstructs an image via filtering a backprojection image of differentiated projection data (FBPD) survives the above fan-beam data truncation problem. Namely, we may exactly reconstruct the whole image object using the truncated data acquired in a full scan mode (2π angular range). We may also exactly reconstruct a small region of interest (ROI) using the truncated projection data acquired in a short-scan mode (less than 2π angular range). The most important characteristic of the proposed reconstruction scheme is that an explicit data rebinning process is not introduced. Numerical simulations were conducted to validate the new reconstruction algorithm

  20. Carboxyl-terminal Truncations of ClC-Kb Abolish Channel Activation by Barttin Via Modified Common Gating and Trafficking.

    Science.gov (United States)

    Stölting, Gabriel; Bungert-Plümke, Stefanie; Franzen, Arne; Fahlke, Christoph

    2015-12-18

    ClC-K chloride channels are crucial for auditory transduction and urine concentration. Mutations in CLCNKB, the gene encoding the renal chloride channel hClC-Kb, cause Bartter syndrome type III, a human genetic condition characterized by polyuria, hypokalemia, and alkalosis. In recent years, several Bartter syndrome-associated mutations have been described that result in truncations of the intracellular carboxyl terminus of hClC-Kb. We here used a combination of whole-cell patch clamp, confocal imaging, co-immunoprecipitation, and surface biotinylation to study the functional consequences of a frequent CLCNKB mutation that creates a premature stop codon at Trp-610. We found that W610X leaves the association of hClC-Kb and the accessory subunit barttin unaffected, but impairs its regulation by barttin. W610X attenuates hClC-Kb surface membrane insertion. Moreover, W610X results in hClC-Kb channel opening in the absence of barttin and prevents further barttin-mediated activation. To describe how the carboxyl terminus modifies the regulation by barttin we used V166E rClC-K1. V166E rClC-K1 is active without barttin and exhibits prominent, barttin-regulated voltage-dependent gating. Electrophysiological characterization of truncated V166E rClC-K1 demonstrated that the distal carboxyl terminus is necessary for slow cooperative gating. Since barttin modifies this particular gating process, channels lacking the distal carboxyl-terminal domain are no longer regulated by the accessory subunit. Our results demonstrate that the carboxyl terminus of hClC-Kb is not part of the binding site for barttin, but functionally modifies the interplay with barttin. The loss-of-activation of truncated hClC-Kb channels in heterologous expression systems fully explains the reduced basolateral chloride conductance in affected kidneys and the clinical symptoms of Bartter syndrome patients. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. Carboxyl-terminal Truncations of ClC-Kb Abolish Channel Activation by Barttin Via Modified Common Gating and Trafficking*

    Science.gov (United States)

    Stölting, Gabriel; Bungert-Plümke, Stefanie; Franzen, Arne; Fahlke, Christoph

    2015-01-01

    ClC-K chloride channels are crucial for auditory transduction and urine concentration. Mutations in CLCNKB, the gene encoding the renal chloride channel hClC-Kb, cause Bartter syndrome type III, a human genetic condition characterized by polyuria, hypokalemia, and alkalosis. In recent years, several Bartter syndrome-associated mutations have been described that result in truncations of the intracellular carboxyl terminus of hClC-Kb. We here used a combination of whole-cell patch clamp, confocal imaging, co-immunoprecipitation, and surface biotinylation to study the functional consequences of a frequent CLCNKB mutation that creates a premature stop codon at Trp-610. We found that W610X leaves the association of hClC-Kb and the accessory subunit barttin unaffected, but impairs its regulation by barttin. W610X attenuates hClC-Kb surface membrane insertion. Moreover, W610X results in hClC-Kb channel opening in the absence of barttin and prevents further barttin-mediated activation. To describe how the carboxyl terminus modifies the regulation by barttin we used V166E rClC-K1. V166E rClC-K1 is active without barttin and exhibits prominent, barttin-regulated voltage-dependent gating. Electrophysiological characterization of truncated V166E rClC-K1 demonstrated that the distal carboxyl terminus is necessary for slow cooperative gating. Since barttin modifies this particular gating process, channels lacking the distal carboxyl-terminal domain are no longer regulated by the accessory subunit. Our results demonstrate that the carboxyl terminus of hClC-Kb is not part of the binding site for barttin, but functionally modifies the interplay with barttin. The loss-of-activation of truncated hClC-Kb channels in heterologous expression systems fully explains the reduced basolateral chloride conductance in affected kidneys and the clinical symptoms of Bartter syndrome patients. PMID:26453302

  2. Cloning and characterization of the major histone H2A genes completes the cloning and sequencing of known histone genes of Tetrahymena thermophila.

    Science.gov (United States)

    Liu, X; Gorovsky, M A

    1996-01-01

    A truncated cDNA clone encoding Tetrahymena thermophila histone H2A2 was isolated using synthetic degenerate oligonucleotide probes derived from H2A protein sequences of Tetrahymena pyriformis. The cDNA clone was used as a homologous probe to isolate a truncated genomic clone encoding H2A1. The remaining regions of the genes for H2A1 (HTA1) and H2A2 (HTA2) were then isolated using inverse PCR on circularized genomic DNA fragments. These partial clones were assembled into intact HTA1 and HTA2 clones. Nucleotide sequences of the two genes were highly homologous within the coding region but not in the noncoding regions. Comparison of the deduced amino acid sequences with protein sequences of T. pyriformis H2As showed only two and three differences respectively, in a total of 137 amino acids for H2A1, and 132 amino acids for H2A2, indicating the two genes arose before the divergence of these two species. The HTA2 gene contains a TAA triplet within the coding region, encoding a glutamine residue. In contrast with the T. thermophila HHO and HTA3 genes, no introns were identified within the two genes. The 5'- and 3'-ends of the histone H2A mRNAs; were determined by RNase protection and by PCR mapping using RACE and RLM-RACE methods. Both genes encode polyadenylated mRNAs and are highly expressed in vegetatively growing cells but only weakly expressed in starved cultures. With the inclusion of these two genes, T. thermophila is the first organism whose entire complement of known core and linker histones, including replication-dependent and basal variants, has been cloned and sequenced. PMID:8760889

  3. Application of the AMPLE cluster-and-truncate approach to NMR structures for molecular replacement

    Energy Technology Data Exchange (ETDEWEB)

    Bibby, Jaclyn [University of Liverpool, Liverpool L69 7ZB (United Kingdom); Keegan, Ronan M. [Research Complex at Harwell, STFC Rutherford Appleton Laboratory, Didcot OX11 0FA (United Kingdom); Mayans, Olga [University of Liverpool, Liverpool L69 7ZB (United Kingdom); Winn, Martyn D. [Science and Technology Facilities Council Daresbury Laboratory, Warrington WA4 4AD (United Kingdom); Rigden, Daniel J., E-mail: drigden@liv.ac.uk [University of Liverpool, Liverpool L69 7ZB (United Kingdom)

    2013-11-01

    Processing of NMR structures for molecular replacement by AMPLE works well. AMPLE is a program developed for clustering and truncating ab initio protein structure predictions into search models for molecular replacement. Here, it is shown that its core cluster-and-truncate methods also work well for processing NMR ensembles into search models. Rosetta remodelling helps to extend success to NMR structures bearing low sequence identity or high structural divergence from the target protein. Potential future routes to improved performance are considered and practical, general guidelines on using AMPLE are provided.

  4. The Extended Erlang-Truncated Exponential distribution: Properties and application to rainfall data.

    Science.gov (United States)

    Okorie, I E; Akpanta, A C; Ohakwe, J; Chikezie, D C

    2017-06-01

    The Erlang-Truncated Exponential ETE distribution is modified and the new lifetime distribution is called the Extended Erlang-Truncated Exponential EETE distribution. Some statistical and reliability properties of the new distribution are given and the method of maximum likelihood estimate was proposed for estimating the model parameters. The usefulness and flexibility of the EETE distribution was illustrated with an uncensored data set and its fit was compared with that of the ETE and three other three-parameter distributions. Results based on the minimized log-likelihood ([Formula: see text]), Akaike information criterion (AIC), Bayesian information criterion (BIC) and the generalized Cramér-von Mises [Formula: see text] statistics shows that the EETE distribution provides a more reasonable fit than the one based on the other competing distributions.

  5. Truncation effects in the functional renormalization group study of spontaneous symmetry breaking

    International Nuclear Information System (INIS)

    Defenu, N.; Mati, P.; Márián, I.G.; Nándori, I.; Trombettoni, A.

    2015-01-01

    We study the occurrence of spontaneous symmetry breaking (SSB) for O(N) models using functional renormalization group techniques. We show that even the local potential approximation (LPA) when treated exactly is sufficient to give qualitatively correct results for systems with continuous symmetry, in agreement with the Mermin-Wagner theorem and its extension to systems with fractional dimensions. For general N (including the Ising model N=1) we study the solutions of the LPA equations for various truncations around the zero field using a finite number of terms (and different regulators), showing that SSB always occurs even where it should not. The SSB is signalled by Wilson-Fisher fixed points which for any truncation are shown to stay on the line defined by vanishing mass beta functions.

  6. Firewalls as artefacts of inconsistent truncations of quantum geometries

    Science.gov (United States)

    Germani, Cristiano; Sarkar, Debajyoti

    2016-01-01

    In this paper we argue that a firewall is simply a manifestation of an inconsistent truncation of non-perturbative effects that unitarize the semiclassical black hole. Namely, we show that a naive truncation of quantum corrections to the Hawking spectrum at order ${\\cal O}(e^{-S})$, inexorably leads to a "localised'' divergent energy density near the black hole horizon. Nevertheless, in the same approximation, a distant observer only sees a discretised spectrum and concludes that unitarity is achieved by ${\\cal O}(e^{-S})$ effects. This is due to the fact that instead, the correct quantum corrections to the Hawking spectrum go like ${\\cal O}( g^{tt} e^{-S})$. Therefore, while at a distance far away from the horizon, where $g^{tt}\\approx 1$, quantum corrections {\\it are} perturbative, they {\\it do} diverge close to the horizon, where $g^{tt}\\rightarrow \\infty$. Nevertheless, these "corrections" nicely re-sum so that correlations functions are smooth at the would-be black hole horizon. Thus, we conclude that the appearance of firewalls is just a signal of the breaking of the semiclassical approximation at the Page time, even for large black holes.

  7. A Novel SCCA Approach via Truncated ℓ1-norm and Truncated Group Lasso for Brain Imaging Genetics.

    Science.gov (United States)

    Du, Lei; Liu, Kefei; Zhang, Tuo; Yao, Xiaohui; Yan, Jingwen; Risacher, Shannon L; Han, Junwei; Guo, Lei; Saykin, Andrew J; Shen, Li

    2017-09-18

    Brain imaging genetics, which studies the linkage between genetic variations and structural or functional measures of the human brain, has become increasingly important in recent years. Discovering the bi-multivariate relationship between genetic markers such as single-nucleotide polymorphisms (SNPs) and neuroimaging quantitative traits (QTs) is one major task in imaging genetics. Sparse Canonical Correlation Analysis (SCCA) has been a popular technique in this area for its powerful capability in identifying bi-multivariate relationships coupled with feature selection. The existing SCCA methods impose either the ℓ 1 -norm or its variants to induce sparsity. The ℓ 0 -norm penalty is a perfect sparsity-inducing tool which, however, is an NP-hard problem. In this paper, we propose the truncated ℓ 1 -norm penalized SCCA to improve the performance and effectiveness of the ℓ 1 -norm based SCCA methods. Besides, we propose an efficient optimization algorithms to solve this novel SCCA problem. The proposed method is an adaptive shrinkage method via tuning τ . It can avoid the time intensive parameter tuning if given a reasonable small τ . Furthermore, we extend it to the truncated group-lasso (TGL), and propose TGL-SCCA model to improve the group-lasso-based SCCA methods. The experimental results, compared with four benchmark methods, show that our SCCA methods identify better or similar correlation coefficients, and better canonical loading profiles than the competing methods. This demonstrates the effectiveness and efficiency of our methods in discovering interesting imaging genetic associations. The Matlab code and sample data are freely available at http://www.iu.edu/∼shenlab/tools/tlpscca/ . © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  8. Association between polymorphisms in cancer-related genes and early onset of esophageal adenocarcinoma.

    Science.gov (United States)

    Wu, I-Chen; Zhao, Yang; Zhai, Rihong; Liu, Geoffrey; Ter-Minassian, Monica; Asomaning, Kofi; Su, Li; Liu, Chen-Yu; Chen, Feng; Kulke, Matthew H; Heist, Rebecca S; Christiani, David C

    2011-04-01

    There is an increasing incidence of esophageal adenocarcinoma (EA) among younger people in the western populations. However, the association between genetic polymorphisms and the age of EA onset is unclear. In this study, 1330 functional/tagging single-nucleotide polymorphisms (SNPs) from 354 cancer-related genes were genotyped in 335 white EA patients. Twenty important SNPs that have the highest importance scores and lowest classification error rate were identified by the random forest algorithm to be associated with early onset of EA (age ≤ 55 years). Subsequent logistic regression analysis indicated that 10 SNPs (rs2070744 of NOS3, rs720321 of BCL2, rs17757541 of BCL2, rs11775256 of TNFRSF10A, rs1035142 of CASP8, rs2236302 of MMP14, rs4740363 of ABL1, rs696217 of GHRL, rs2445762 of CYP19A1, and rs11941492 of VEGFR2/KDR) were significantly associated with early onset of EA (≤55 vs >55 years, all P polymorphisms in cancer-related genes, especially those in the apoptotic pathway, play an important role in the development of younger-aged EA in a dose-response manner.

  9. Reduction of truncation errors in planar near-field aperture antenna measurements using the method of alternating orthogonal projections

    DEFF Research Database (Denmark)

    Martini, Enrica; Breinbjerg, Olav; Maci, Stefano

    2006-01-01

    A simple and effective procedure for the reduction of truncation error in planar near-field to far-field transformations is presented. The starting point is the consideration that the actual scan plane truncation implies a reliability of the reconstructed plane wave spectrum of the field radiated...

  10. Different truncation methods of AUC between Japan and the EU for bioequivalence assessment: influence on the regulatory judgment.

    Science.gov (United States)

    Oishi, Masayo; Chiba, Koji; Fukushima, Takashi; Tomono, Yoshiro; Suwa, Toshio

    2012-01-01

    In regulatory guidelines for bioequivalence (BE) assessment, the definitions of AUC for primary assessment are different in ICH countries, i.e., AUC from zero to the last sampling point (AUCall) in Japan, AUC from zero to infinity (AUCinf) or AUC from zero to the last measurable point (AUClast) in the US, and AUClast in the EU. To assure sufficient accuracy of truncated AUC for BE assessment, the ratio of truncated AUC (AUCall or AUClast) to AUCinf should be more than 80% both in Japanese and EU guidelines. We investigated how the difference in the definition of truncated AUC affects BE assessment of sustained release (SR) formulation. Our simulation result demonstrated that AUCall/AUCinf could be ≥80% despite AUClast/AUCinf being AUC affected the judgment of validity of truncated AUC for BE assessment, and AUCall could fail to detect the substantially different in vivo dissolution profile of generic drugs with SR formulation from the original drug.

  11. Furin is a chemokine-modifying enzyme: in vitro and in vivo processing of CXCL10 generates a C-terminally truncated chemokine retaining full activity.

    Science.gov (United States)

    Hensbergen, Paul J; Verzijl, Dennis; Balog, Crina I A; Dijkman, Remco; van der Schors, Roel C; van der Raaij-Helmer, Elizabeth M H; van der Plas, Mariena J A; Leurs, Rob; Deelder, André M; Smit, Martine J; Tensen, Cornelis P

    2004-04-02

    Chemokines comprise a class of structurally related proteins that are involved in many aspects of leukocyte migration under basal and inflammatory conditions. In addition to the large number of genes, limited processing of these proteins by a variety of enzymes enhances the complexity of the total spectrum of chemokine variants. We have recently shown that the native chemokine CXCL10 is processed at the C terminus, thereby shedding the last four amino acids. The present study was performed to elucidate the mechanism in vivo and in vitro and to study the biological activity of this novel isoform of CXCL10. Using a combination of protein purification and mass spectrometric techniques, we show that the production of C-terminally truncated CXCL10 by primary keratinocytes is inhibited in vivo by a specific inhibitor of pro-protein convertases (e.g. furin) but not by inhibition of matrix metalloproteinases. Moreover, CXCL10 is processed by furin in vitro, which is abrogated by a mutation in the furin recognition site. Using GTPgammaS binding, Ca(2+) mobilization, and chemotaxis assays, we demonstrate that the C-terminally truncated CXCL10 variant is a potent ligand for CXCR3. Moreover, the inverse agonist activity on the virally encoded receptor ORF74 and the direct antibacterial activity of CXCL10 are fully retained. Hence, we have identified furin as a novel chemokine-modifying enzyme in vitro and most probably also in vivo, generating a C-terminally truncated CXCL10, which fully retains its (inverse) agonistic properties.

  12. Construction and heterologous expression of a truncated Haemagglutinin (HA) protein from the avian influenza virus H5N1 in Escherichia coli.

    Science.gov (United States)

    Chee Wei, T; Nurul Wahida, A G; Shaharum, S

    2014-12-01

    Malaysia first reported H5N1 poultry case in 2004 and subsequently outbreak in poultry population in 2007. Here, a recombinant gene encoding of peptide epitopes, consisting fragments of HA1, HA2 and a polybasic cleavage site of H5N1 strain Malaysia, was amplified and cloned into pET-47b(+) bacterial expression vector. DNA sequencing and alignment analysis confirmed that the gene had no alteration and in-frame to the vector. Then, His-tagged truncated HA protein was expressed in Escherichia coli BL21 (DE3) under 1 mM IPTG induction. The protein expression was optimized under a time-course induction study and further purified using Ni-NTA agarose under reducing condition. Migration size of protein was detected at 15 kDa by Western blot using anti-His tag monoclonal antibody and demonstrated no discrepancy compared to its calculated molecular weight.

  13. Aedes aegypti on Madeira Island (Portugal): genetic variation of a recently introduced dengue vector.

    Science.gov (United States)

    Seixas, Gonçalo; Salgueiro, Patrícia; Silva, Ana Clara; Campos, Melina; Spenassatto, Carine; Reyes-Lugo, Matías; Novo, Maria Teresa; Ribolla, Paulo Eduardo Martins; Silva Pinto, João Pedro Soares da; Sousa, Carla Alexandra

    2013-01-01

    The increasing population of Aedes aegypti mosquitoes on Madeira Island (Portugal) resulted in the first autochthonous dengue outbreak, which occurred in October 2012. Our study establishes the first genetic evaluation based on the mitochondrial DNA (mtDNA) genes [cytochrome oxidase subunit I (COI) and NADH dehydrogenase subunit 4 (ND4)] and knockdown resistance (kdr) mutations exploring the colonisation history and the genetic diversity of this insular vector population. We included mosquito populations from Brazil and Venezuela in the analysis as putative geographic sources. The Ae. aegypti population from Madeira showed extremely low mtDNA genetic variability, with a single haplotype for COI and ND4. We also detected the presence of two important kdr mutations and the quasi-fixation of one of these mutations (F1534C). These results are consistent with a unique recent founder event that occurred on the island of Ae. aegypti mosquitoes that carry kdr mutations associated with insecticide resistance. Finally, we also report the presence of the F1534C kdr mutation in the Brazil and Venezuela populations. To our knowledge, this is the first time this mutation has been found in South American Ae. aegypti mosquitoes. Given the present risk of Ae. aegypti re-invading continental Europe from Madeira and the recent dengue outbreaks on the island, this information is important to plan surveillance and control measures.

  14. Vascular Endothelial Growth Factor Receptor-2 Polymorphisms Have Protective Effect against the Development of Tendinopathy in Volleyball Athletes.

    Science.gov (United States)

    Salles, José Inácio; Duarte, Maria Eugenia Leite; Guimarães, João Matheus; Lopes, Lucas Rafael; Vilarinho Cardoso, Jessica; Aguiar, Diego Pinheiro; Machado Neto, João Olyntho; Machado, Daniel Escorsim; Perini, Jamila Alessandra

    2016-01-01

    The aim of the study was to investigate whether genetic variants in VEGF and KDR genes can be correlated with susceptibility of tendinopathy in volleyball athletes. This study was conducted at the Brazilian Volleyball Federation, and comprised 179 volleyball athletes: 88 had a confirmed diagnosis of tendinopathy (cases), whereas 91 had no evidence of the disease (controls). The VEGF (-2578C>A, -460T>C and +936C>T) and KDR (-604C>T, 1192G>A and 1719T>A) polymorphisms were determined by TaqMan real-time polymerase chain reaction. The odds ratio (OR) with their 95% confidence intervals (CI) were calculated using an unconditional logistic regression model. The evaluation of demographic and clinical characteristics revealed the athlete age (P volleyball (P T, 1192G>A and 1719T>A) haplotypes CGA and CAT were associated with decreased tendinopathy risk (OR: 0.46, 95% CI: 0.21-0.99 and OR: 0.23, 95% CI: 0.07-0.76, respectively). With regards to pain, traumatic lesion and away from training due to injury, VEGF and KDR polymorphisms were not associated with clinical symptoms complaints. The present results provide evidence that the KDR polymorphisms were associated with development of tendinopathy, and can contribute to identify new therapeutic targets or personalized training programs to avoid tendinopathy development in athletes.

  15. The Extended Erlang-Truncated Exponential distribution: Properties and application to rainfall data

    Directory of Open Access Journals (Sweden)

    I.E. Okorie

    2017-06-01

    Full Text Available The Erlang-Truncated Exponential ETE distribution is modified and the new lifetime distribution is called the Extended Erlang-Truncated Exponential EETE distribution. Some statistical and reliability properties of the new distribution are given and the method of maximum likelihood estimate was proposed for estimating the model parameters. The usefulness and flexibility of the EETE distribution was illustrated with an uncensored data set and its fit was compared with that of the ETE and three other three-parameter distributions. Results based on the minimized log-likelihood (−ℓˆ, Akaike information criterion (AIC, Bayesian information criterion (BIC and the generalized Cramér–von Mises W⋆ statistics shows that the EETE distribution provides a more reasonable fit than the one based on the other competing distributions. Keywords: Mathematics, Applied mathematics

  16. Classification With Truncated Distance Kernel.

    Science.gov (United States)

    Huang, Xiaolin; Suykens, Johan A K; Wang, Shuning; Hornegger, Joachim; Maier, Andreas

    2018-05-01

    This brief proposes a truncated distance (TL1) kernel, which results in a classifier that is nonlinear in the global region but is linear in each subregion. With this kernel, the subregion structure can be trained using all the training data and local linear classifiers can be established simultaneously. The TL1 kernel has good adaptiveness to nonlinearity and is suitable for problems which require different nonlinearities in different areas. Though the TL1 kernel is not positive semidefinite, some classical kernel learning methods are still applicable which means that the TL1 kernel can be directly used in standard toolboxes by replacing the kernel evaluation. In numerical experiments, the TL1 kernel with a pregiven parameter achieves similar or better performance than the radial basis function kernel with the parameter tuned by cross validation, implying the TL1 kernel a promising nonlinear kernel for classification tasks.

  17. Filter Factors of Truncated TLS Regularization with Multiple Observations

    Czech Academy of Sciences Publication Activity Database

    Hnětynková, I.; Plešinger, Martin; Žáková, J.

    2017-01-01

    Roč. 62, č. 2 (2017), s. 105-120 ISSN 0862-7940 R&D Projects: GA ČR GA13-06684S Institutional support: RVO:67985807 Keywords : truncated total least squares * multiple right-hand sides * eigenvalues of rank-d update * ill-posed problem * regularization * filter factors Subject RIV: BA - General Mathematics OBOR OECD: Applied mathematics Impact factor: 0.618, year: 2016 http://hdl.handle.net/10338.dmlcz/146698

  18. Error Bounds for Augmented Truncations of Discrete-Time Block-Monotone Markov Chains under Geometric Drift Conditions

    OpenAIRE

    Masuyama, Hiroyuki

    2014-01-01

    In this paper we study the augmented truncation of discrete-time block-monotone Markov chains under geometric drift conditions. We first present a bound for the total variation distance between the stationary distributions of an original Markov chain and its augmented truncation. We also obtain such error bounds for more general cases, where an original Markov chain itself is not necessarily block monotone but is blockwise dominated by a block-monotone Markov chain. Finally,...

  19. Free vibration of symmetric angle ply truncated conical shells under different boundary conditions using spline method

    Energy Technology Data Exchange (ETDEWEB)

    Viswanathan, K. K.; Aziz, Z. A.; Javed, Saira; Yaacob, Y. [Universiti Teknologi Malaysia, Johor Bahru (Malaysia); Pullepu, Babuji [S R M University, Chennai (India)

    2015-05-15

    Free vibration of symmetric angle-ply laminated truncated conical shell is analyzed to determine the effects of frequency parameter and angular frequencies under different boundary condition, ply angles, different material properties and other parameters. The governing equations of motion for truncated conical shell are obtained in terms of displacement functions. The displacement functions are approximated by cubic and quintic splines resulting into a generalized eigenvalue problem. The parametric studies have been made and discussed.

  20. Free vibration of symmetric angle ply truncated conical shells under different boundary conditions using spline method

    International Nuclear Information System (INIS)

    Viswanathan, K. K.; Aziz, Z. A.; Javed, Saira; Yaacob, Y.; Pullepu, Babuji

    2015-01-01

    Free vibration of symmetric angle-ply laminated truncated conical shell is analyzed to determine the effects of frequency parameter and angular frequencies under different boundary condition, ply angles, different material properties and other parameters. The governing equations of motion for truncated conical shell are obtained in terms of displacement functions. The displacement functions are approximated by cubic and quintic splines resulting into a generalized eigenvalue problem. The parametric studies have been made and discussed.

  1. Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail

    Directory of Open Access Journals (Sweden)

    Takeo eKuwata

    2013-05-01

    Full Text Available The role of antibodies in protecting the host from human immunodeficiency virus type 1 (HIV-1 infection is of considerable interest, particularly because the RV144 trial results suggest that antibodies contribute to protection. Although infection of nonhuman primates with simian immunodeficiency virus (SIV is commonly used as an animal model of HIV-1 infection, the viral epitopes that elicit potent and broad neutralizing antibodies to SIV have not been identified. We isolated a monoclonal antibody (MAb B404 that potently and broadly neutralizes various SIV strains. B404 targets a conformational epitope comprising the V3 and V4 loops of Env that intensely exposed when Env binds CD4. B404-resistant variants were obtained by passaging viruses in the presence of increasing concentration of B404 in PM1/CCR5 cells. Genetic analysis revealed that the Q733stop mutation, which truncates the cytoplasmic tail of gp41, was the first major substitution in Env during passage. The maximal inhibition by B404 and other MAbs were significantly decreased against a recombinant virus with a gp41 truncation compared with the parental SIVmac316. This indicates that the gp41 truncation was associated with resistance to antibody-mediated neutralization. The infectivities of the recombinant virus with the gp41 truncation were 7900-fold, 1000-fold, and 140-fold higher than those of SIVmac316 in PM1, PM1/CCR5, and TZM-bl cells, respectively. Immunoblotting analysis revealed that the gp41 truncation enhanced the incorporation of Env into virions. The effect of the gp41 truncation on infectivity was not obvious in the HSC-F macaque cell line, although the resistance of viruses harboring the gp41 truncation to neutralization was maintained. These results suggest that viruses with a truncated gp41 cytoplasmic tail were selected by increased infectivity in human cells and by acquiring resistance to neutralizing antibody.

  2. The lamppost model: effects of photon trapping, the bottom lamp and disc truncation

    Science.gov (United States)

    Niedźwiecki, Andrzej; Zdziarski, Andrzej A.

    2018-04-01

    We study the lamppost model, in which the primary X-ray sources in accreting black-hole systems are located symmetrically on the rotation axis on both sides of the black hole surrounded by an accretion disc. We show the importance of the emission of the source on the opposite side to the observer. Due to gravitational light bending, its emission can increase the direct (i.e., not re-emitted by the disc) flux by as much as an order of magnitude. This happens for near to face-on observers when the disc is even moderately truncated. For truncated discs, we also consider effects of emission of the top source gravitationally bent around the black hole. We also present results for the attenuation of the observed radiation with respect to that emitted by the lamppost as functions of the lamppost height, black-hole spin and the degree of disc truncation. This attenuation, which is due to the time dilation, gravitational redshift and the loss of photons crossing the black-hole horizon, can be as severe as by several orders of magnitude for low lamppost heights. We also consider the contribution to the observed flux due to re-emission by optically-thick matter within the innermost stable circular orbit.

  3. Spectroscopic characterization of a truncated hemoglobin from the nitrogen-fixing bacterium Herbaspirillum seropedicae.

    Science.gov (United States)

    Razzera, Guilherme; Vernal, Javier; Baruh, Debora; Serpa, Viviane I; Tavares, Carolina; Lara, Flávio; Souza, Emanuel M; Pedrosa, Fábio O; Almeida, Fábio C L; Terenzi, Hernán; Valente, Ana Paula

    2008-09-01

    The Herbaspirillum seropedicae genome sequence encodes a truncated hemoglobin typical of group II (Hs-trHb1) members of this family. We show that His-tagged recombinant Hs-trHb1 is monomeric in solution, and its optical spectrum resembles those of previously reported globins. NMR analysis allowed us to assign heme substituents. All data suggest that Hs-trHb1 undergoes a transition from an aquomet form in the ferric state to a hexacoordinate low-spin form in the ferrous state. The close positions of Ser-E7, Lys-E10, Tyr-B10, and His-CD1 in the distal pocket place them as candidates for heme coordination and ligand regulation. Peroxide degradation kinetics suggests an easy access to the heme pocket, as the protein offered no protection against peroxide degradation when compared with free heme. The high solvent exposure of the heme may be due to the presence of a flexible loop in the access pocket, as suggested by a structural model obtained by using homologous globins as templates. The truncated hemoglobin described here has unique features among truncated hemoglobins and may function in the facilitation of O(2) transfer and scavenging, playing an important role in the nitrogen-fixation mechanism.

  4. Novel nonsense mutation in the katA gene of a catalase-negative Staphylococcus aureus strain.

    Science.gov (United States)

    Lagos, Jaime; Alarcón, Pedro; Benadof, Dona; Ulloa, Soledad; Fasce, Rodrigo; Tognarelli, Javier; Aguayo, Carolina; Araya, Pamela; Parra, Bárbara; Olivares, Berta; Hormazábal, Juan Carlos; Fernández, Jorge

    2016-01-01

    We report the first description of a rare catalase-negative strain of Staphylococcus aureus in Chile. This new variant was isolated from blood and synovial tissue samples of a pediatric patient. Sequencing analysis revealed that this catalase-negative strain is related to ST10 strain, which has earlier been described in relation to S. aureus carriers. Interestingly, sequence analysis of the catalase gene katA revealed presence of a novel nonsense mutation that causes premature translational truncation of the C-terminus of the enzyme leading to a loss of 222 amino acids. Our study suggests that loss of catalase activity in this rare catalase-negative Chilean strain is due to this novel nonsense mutation in the katA gene, which truncates the enzyme to just 283 amino acids. Copyright © 2015 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

  5. Blunt traumatic axillary artery truncation, in the absence of associated fracture.

    Science.gov (United States)

    Bokser, Emily; Caputo, William; Hahn, Barry; Greenstein, Josh

    2018-02-01

    Axillary artery injuries can be associated with both proximal humeral fractures (Naouli et al., 2016; Ng et al., 2016) [1,2] as well as shoulder dislocations (Leclerc et al., 2017; Karnes et al., 2016) [3,4]. We report a rare case of an isolated axillary artery truncation following blunt trauma without any associated fracture or dislocation. A 58-year-old male presented to the emergency department for evaluation after falling on his outstretched right arm. The patient was found to have an absent right radial pulse with decreased sensation to the right arm. Point of care ultrasound showed findings suspicious for traumatic axillary artery injury, and X-rays did not demonstrate any fracture. Computed tomography with angiography confirmed axillary artery truncation with active extravasation. The patient underwent successful vascular repair with an axillary artery bypass. Although extremity injuries are common in emergency departments, emergency physicians need to recognize the risk for vascular injuries, even without associated fracture or dislocation. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Genes Encoding Aluminum-Activated Malate Transporter II and their Association with Fruit Acidity in Apple

    Directory of Open Access Journals (Sweden)

    Baiquan Ma

    2015-11-01

    Full Text Available A gene encoding aluminum-activated malate transporter (ALMT was previously reported as a candidate for the locus controlling acidity in apple ( × Borkh.. In this study, we found that apple genes can be divided into three families and the gene belongs to the family. Duplication of genes in apple is related to the polyploid origin of the apple genome. Divergence in expression has occurred between the gene and its homologs in the family and only the gene is significantly associated with malic acid content. The locus consists of two alleles, and . resides in the tonoplast and its ectopic expression in yeast was found to increase the influx of malic acid into yeast cells significantly, suggesting it may function as a vacuolar malate channel. In contrast, encodes a truncated protein because of a single nucleotide substitution of G with A in the last exon. As this truncated protein resides within the cell membrane, it is deemed to be nonfunctional as a vacuolar malate channel. The frequency of the genotype is very low in apple cultivars but is high in wild relatives, which suggests that apple domestication may be accompanied by selection for the gene. In addition, variations in the malic acid content of mature fruits were also observed between accessions with the same genotype in the locus. This suggests that the gene is not the only genetic determinant of fruit acidity in apple.

  7. Firewalls as artefacts of inconsistent truncations of quantum geometries

    Energy Technology Data Exchange (ETDEWEB)

    Germani, Cristiano [Max-Planck-Institut fuer Physik, Muenchen (Germany); Arnold Sommerfeld Center, Ludwig-Maximilians-University, Muenchen (Germany); Institut de Ciencies del Cosmos, Universitat de Barcelona (Spain); Sarkar, Debajyoti [Max-Planck-Institut fuer Physik, Muenchen (Germany); Arnold Sommerfeld Center, Ludwig-Maximilians-University, Muenchen (Germany)

    2016-01-15

    In this paper we argue that a firewall is simply a manifestation of an inconsistent truncation of non-perturbative effects that unitarize the semiclassical black hole. Namely, we show that a naive truncation of quantum corrections to the Hawking spectrum at order O(e{sup -S}), inexorably leads to a ''localised'' divergent energy density near the black hole horizon. Nevertheless, in the same approximation, a distant observer only sees a discretised spectrum and concludes that unitarity is achieved by (e{sup -S}) effects. This is due to the fact that instead, the correct quantum corrections to the Hawking spectrum go like (g{sup tt}e{sup -S}). Therefore, while at a distance far away from the horizon, where g{sup tt} ∼ 1, quantum corrections are perturbative, they do diverge close to the horizon, where g{sup tt} → ∞. Nevertheless, these ''corrections'' nicely re-sum so that correlations functions are smooth at the would-be black hole horizon. Thus, we conclude that the appearance of firewalls is just a signal of the breaking of the semiclassical approximation at the Page time, even for large black holes. (copyright 2015 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  8. Firewalls as artefacts of inconsistent truncations of quantum geometries

    International Nuclear Information System (INIS)

    Germani, Cristiano; Sarkar, Debajyoti

    2016-01-01

    In this paper we argue that a firewall is simply a manifestation of an inconsistent truncation of non-perturbative effects that unitarize the semiclassical black hole. Namely, we show that a naive truncation of quantum corrections to the Hawking spectrum at order O(e -S ), inexorably leads to a ''localised'' divergent energy density near the black hole horizon. Nevertheless, in the same approximation, a distant observer only sees a discretised spectrum and concludes that unitarity is achieved by (e -S ) effects. This is due to the fact that instead, the correct quantum corrections to the Hawking spectrum go like (g tt e -S ). Therefore, while at a distance far away from the horizon, where g tt ∼ 1, quantum corrections are perturbative, they do diverge close to the horizon, where g tt → ∞. Nevertheless, these ''corrections'' nicely re-sum so that correlations functions are smooth at the would-be black hole horizon. Thus, we conclude that the appearance of firewalls is just a signal of the breaking of the semiclassical approximation at the Page time, even for large black holes. (copyright 2015 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  9. Detecting and correcting for publication bias in meta-analysis - A truncated normal distribution approach.

    Science.gov (United States)

    Zhu, Qiaohao; Carriere, K C

    2016-01-01

    Publication bias can significantly limit the validity of meta-analysis when trying to draw conclusion about a research question from independent studies. Most research on detection and correction for publication bias in meta-analysis focus mainly on funnel plot-based methodologies or selection models. In this paper, we formulate publication bias as a truncated distribution problem, and propose new parametric solutions. We develop methodologies of estimating the underlying overall effect size and the severity of publication bias. We distinguish the two major situations, in which publication bias may be induced by: (1) small effect size or (2) large p-value. We consider both fixed and random effects models, and derive estimators for the overall mean and the truncation proportion. These estimators will be obtained using maximum likelihood estimation and method of moments under fixed- and random-effects models, respectively. We carried out extensive simulation studies to evaluate the performance of our methodology, and to compare with the non-parametric Trim and Fill method based on funnel plot. We find that our methods based on truncated normal distribution perform consistently well, both in detecting and correcting publication bias under various situations.

  10. Organisation and melting of solution grown truncated lozenge polyethylene single crystals

    NARCIS (Netherlands)

    Loos, J.; Tian, M.

    2003-01-01

    Morphological features and the melting behaviour of truncated lozenge crystals have been studied. For the crystals investigated, the heights of the (110) and the (200) sectors were measured to be 14.5 and 12.7 nm, respectively, using atomic force microscopy (AFM) in contact and non-contact mode.

  11. POC1A truncation mutation causes a ciliopathy in humans characterized by primordial dwarfism.

    Science.gov (United States)

    Shaheen, Ranad; Faqeih, Eissa; Shamseldin, Hanan E; Noche, Ramil R; Sunker, Asma; Alshammari, Muneera J; Al-Sheddi, Tarfa; Adly, Nouran; Al-Dosari, Mohammed S; Megason, Sean G; Al-Husain, Muneera; Al-Mohanna, Futwan; Alkuraya, Fowzan S

    2012-08-10

    Primordial dwarfism (PD) is a phenotype characterized by profound growth retardation that is prenatal in onset. Significant strides have been made in the last few years toward improved understanding of the molecular underpinning of the limited growth that characterizes the embryonic and postnatal development of PD individuals. These include impaired mitotic mechanics, abnormal IGF2 expression, perturbed DNA-damage response, defective spliceosomal machinery, and abnormal replication licensing. In three families affected by a distinct form of PD, we identified a founder truncating mutation in POC1A. This gene is one of two vertebrate paralogs of POC1, which encodes one of the most abundant proteins in the Chlamydomonas centriole proteome. Cells derived from the index individual have abnormal mitotic mechanics with multipolar spindles, in addition to clearly impaired ciliogenesis. siRNA knockdown of POC1A in fibroblast cells recapitulates this ciliogenesis defect. Our findings highlight a human ciliopathy syndrome caused by deficiency of a major centriolar protein. Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  12. Efficient Tridiagonal Preconditioner for the Matrix-Free Truncated Newton Method

    Czech Academy of Sciences Publication Activity Database

    Lukšan, Ladislav; Vlček, Jan

    2014-01-01

    Roč. 235, 25 May (2014), s. 394-407 ISSN 0096-3003 R&D Projects: GA ČR GA13-06684S Institutional support: RVO:67985807 Keywords : unconstrained optimization * large scale optimization * matrix-free truncated Newton method * preconditioned conjugate gradient method * preconditioners obtained by the directional differentiation * numerical algorithms Subject RIV: BA - General Mathematics Impact factor: 1.551, year: 2014

  13. Question of the total gene number in Drosophila melanogaster

    International Nuclear Information System (INIS)

    Lefevre, G.; Watkins, W.

    1986-01-01

    A statistical analysis has been carried out on the distribution and allelism of nearly 500 sex-linked, X-ray-induced, cytologically normal and rearranged lethal mutations in Drosophila melanogaster that were obtained by G. Lefevre. The mutations were induced in four different regions of the X chromosome: (1) 1A1-3E8, (2) 6D1-8A5, (3) 9E1-11A7 and (4) 19A1-20F4, which together comprise more than one-third of the entire chromosome.--The analysis shows that the number of alleles found at different loci does not fit a Poisson distribution, even when the proper procedures are taken to accommodate the truncated nature of the data. However, the allele distribution fits a truncated negative binomial distribution quite well, with cytologically normal mutations fitting better than rearrangement mutations. This indicates that genes are not equimutable, as required for the data to fit a Poisson distribution.--Using the negative binomial parameters to estimate the number of genes that did not produce a detectable lethal mutation in our experiment (n0) gave a larger number than that derived from the use of the Poisson parameter. Unfortunately, we cannot estimate the total numbers of nonvital loci, loci with undetectable phenotypes and loci having extremely low mutabilities. In any event, our estimate of the total vital gene number was far short of the total number of bands in the analyzed regions; yet, in several short intervals, we have found more vital genes than bands; in other intervals, fewer. We conclude that the one-band, one-gene hypothesis, in its literal sense, is not true; furthermore, it is difficult to support, even approximately.--The question of the total gene number in Drosophila will, not doubt, eventually be solved by molecular analyses, not by statistical analysis of mutation data or saturation studies

  14. Loss of ACTH expression in cultured human corticotroph macroadenoma cells is consistent with loss of the POMC gene signal sequence.

    Science.gov (United States)

    Rees, D A; Hepburn, P J; McNicol, A M; Francis, K; Jasani, B; Lewis, M D; Farrell, W E; Lewis, B M; Scanlon, M F; Ham, J

    2002-03-28

    The proopiomelanocortin (POMC) gene is highly expressed in the pituitary gland where the resulting mRNA of 1200 base pairs (bp) gives rise to a full-length protein sequence. In peripheral tissues however both shorter and longer POMC variants have been described, these include for example placental tissue which contain 800 (truncated at the 5' end) and 1500 as well as the 1200 bp transcripts. The importance of the 800 bp transcript is unclear as the lack of a signal sequence renders the molecule to be non-functional. This transcript has not been previously demonstrated in the pituitary gland. In this report we show evidence of a 5' truncated POMC gene in human pituitary corticotroph macroadenoma cells (JE) maintained in primary culture for >1 year. The original tumour tissue and the derived cells during early passage (up to passage 4-5) immunostained for ACTH and in situ hybridisation confirmed the presence of the POMC gene in the cultured cells. These cells also secreted 15-40 pg/10(5) cells/24 h ACTH. In addition, as expected RT-PCR demonstrated the presence of all three POMC gene exons and is thus indicative of a full-length POMC gene. In late culture passages (passages 8-15) JE cells ceased to express ACTH and cell growth became very slow due presumably to cells reaching their Hayflick limit. ACTH immunostaining in these cells was undetectable and ACTH secretion was also at the detection limits of the assay and no greater than 10 pg/10(5) cells/24 h. ACTH precursor molecules were also undetectable. RT-PCR for the POMC gene in these late passage cells showed that only exon 3 was detectable, in contrast to early passage cells where all three exons were present. In summary we isolated in culture, human pituitary cells that possessed initially all three exons of the POMC gene and immunostained for ACTH. On further passaging these cells showed a loss of exons 1 and 2 in the POMC gene and a loss of ACTH immunostaining and secretion. We would like to suggest that the

  15. Family losses following truncation selection in populations of half-sib families

    Science.gov (United States)

    J. H. Roberds; G. Namkoong; H. Kang

    1980-01-01

    Family losses during truncation selection may be sizable in populations of half-sib families. Substantial losses may occur even in populations containing little or no variation among families. Heavier losses will occur, however, under conditions of high heritability where there is considerable family variation. Standard deviations and therefore variances of family loss...

  16. Identification of a novel truncating PALB2 mutation and analysis of its contribution to early-onset breast cancer in French-Canadian women.

    Science.gov (United States)

    Foulkes, William D; Ghadirian, Parviz; Akbari, Mohammed Reza; Hamel, Nancy; Giroux, Sylvie; Sabbaghian, Nelly; Darnel, Andrew; Royer, Robert; Poll, Aletta; Fafard, Eve; Robidoux, André; Martin, Ginette; Bismar, Tarek A; Tischkowitz, Marc; Rousseau, Francois; Narod, Steven A

    2007-01-01

    PALB2 has recently been identified as a breast cancer susceptibility gene. PALB2 mutations are rare causes of hereditary breast cancer but may be important in countries such as Finland where a founder mutation is present. We sought to estimate the contribution of PALB2 mutations to the burden of breast cancer in French Canadians from Quebec. We screened all coding exons of PALB2 in a sample of 50 French-Canadian women diagnosed with either early-onset breast cancer or familial breast cancer at a single Montreal hospital. The genetic variants identified in this sample were then studied in 356 additional women with breast cancer diagnosed before age 50 and in 6,448 newborn controls. We identified a single protein-truncating mutation in PALB2 (c.2323 C>T, resulting in Q775X) in 1 of the 50 high-risk women. This variant was present in 2 of 356 breast cancer cases and in none of 6,440 newborn French-Canadian controls (P = 0.003). We also identified two novel new non-synonymous single nucleotide polymorphisms in exon 4 of PALB2 (c.5038 A>G [I76V] and c.5156 G>T [G115V]). G115V was found in 1 of 356 cases and in 15 of 6,442 controls (P = 0.6). The I76V variant was not identified in either the extended case series or the controls. We have identified a novel truncating mutation in PALB2. The mutation was found in approximately 0.5% of unselected French-Canadian women with early-onset breast cancer and appears to have a single origin. Although mutations are infrequent, PALB2 can be added to the list of breast cancer susceptibility genes for which founder mutations have been identified in the French-Canadian population.

  17. ERK and PI3K regulate different aspects of the epithelial to mesenchymal transition of mammary tumor cells induced by truncated MUC1

    International Nuclear Information System (INIS)

    Horn, Galit; Gaziel, Avital; Wreschner, Daniel H.; Smorodinsky, Nechama I.; Ehrlich, Marcelo

    2009-01-01

    Epithelial to mesenchymal transition (EMT) integrates changes to cell morphology and signaling pathways resulting from modifications to the cell's transcriptional response. Different combinations of stimuli ignite this process in the contexts of development or tumor progression. The human MUC1 gene encodes multiple alternatively spliced forms of a polymorphic oncoprotein that is aberrantly expressed in epithelial malignancies. MUC1 is endowed with various signaling modules and has the potential to mediate proliferative and morphological changes characteristic of the progression of epithelial tumors. The tyrosine-rich cytoplasmic domain and the heavily glycosylated extracellular domain both play a role in MUC1-mediated signal transduction. However, the attribution of function to specific domains of MUC1 is difficult due to the concomitant presence of multiple forms of the protein, which stem from alternative splicing and proteolytic cleavage. Here we show that DA3 mouse mammary tumor cells stably transfected with a truncated genomic fragment of human MUC1 undergo EMT. In their EMT, these cells demonstrate altered [i] morphology, [ii] signaling pathways and [iii] expression of epithelial and mesenchymal markers. Similarly to well characterized human breast cancer cell lines, cells transfected with truncated MUC1 show an ERK-dependent increased spreading on fibronectin, and a PI3K-dependent enhancement of their proliferative rate.

  18. The application of nonsense-mediated mRNA decay inhibition to the identification of breast cancer susceptibility genes

    International Nuclear Information System (INIS)

    Johnson, Julie K; Waddell, Nic; Chenevix-Trench, Georgia

    2012-01-01

    Identification of novel, highly penetrant, breast cancer susceptibility genes will require the application of additional strategies beyond that of traditional linkage and candidate gene approaches. Approximately one-third of inherited genetic diseases, including breast cancer susceptibility, are caused by frameshift or nonsense mutations that truncate the protein product [1]. Transcripts harbouring premature termination codons are selectively and rapidly degraded by the nonsense-mediated mRNA decay (NMD) pathway. Blocking the NMD pathway in any given cell will stabilise these mutant transcripts, which can then be detected using gene expression microarrays. This technique, known as gene identification by nonsense-mediated mRNA decay inhibition (GINI), has proved successful in identifying sporadic nonsense mutations involved in many different cancer types. However, the approach has not yet been applied to identify germline mutations involved in breast cancer. We therefore attempted to use GINI on lymphoblastoid cell lines (LCLs) from multiple-case, non- BRCA1/2 breast cancer families in order to identify additional high-risk breast cancer susceptibility genes. We applied GINI to a total of 24 LCLs, established from breast-cancer affected and unaffected women from three multiple-case non-BRCA1/2 breast cancer families. We then used Illumina gene expression microarrays to identify transcripts stabilised by the NMD inhibition. The expression profiling identified a total of eight candidate genes from these three families. One gene, PPARGC1A, was a candidate in two separate families. We performed semi-quantitative real-time reverse transcriptase PCR of all candidate genes but only PPARGC1A showed successful validation by being stabilised in individuals with breast cancer but not in many unaffected members of the same family. Sanger sequencing of all coding and splice site regions of PPARGC1A did not reveal any protein truncating mutations. Haplotype analysis using short

  19. Multiple Gene-Environment Interactions on the Angiogenesis Gene-Pathway Impact Rectal Cancer Risk and Survival

    Directory of Open Access Journals (Sweden)

    Noha Sharafeldin

    2017-09-01

    Full Text Available Characterization of gene-environment interactions (GEIs in cancer is limited. We aimed at identifying GEIs in rectal cancer focusing on a relevant biologic process involving the angiogenesis pathway and relevant environmental exposures: cigarette smoking, alcohol consumption, and animal protein intake. We analyzed data from 747 rectal cancer cases and 956 controls from the Diet, Activity and Lifestyle as a Risk Factor for Rectal Cancer study. We applied a 3-step analysis approach: first, we searched for interactions among single nucleotide polymorphisms on the pathway genes; second, we searched for interactions among the genes, both steps using Logic regression; third, we examined the GEIs significant at the 5% level using logistic regression for cancer risk and Cox proportional hazards models for survival. Permutation-based test was used for multiple testing adjustment. We identified 8 significant GEIs associated with risk among 6 genes adjusting for multiple testing: TNF (OR = 1.85, 95% CI: 1.10, 3.11, TLR4 (OR = 2.34, 95% CI: 1.38, 3.98, and EGR2 (OR = 2.23, 95% CI: 1.04, 4.78 with smoking; IGF1R (OR = 1.69, 95% CI: 1.04, 2.72, TLR4 (OR = 2.10, 95% CI: 1.22, 3.60 and EGR2 (OR = 2.12, 95% CI: 1.01, 4.46 with alcohol; and PDGFB (OR = 1.75, 95% CI: 1.04, 2.92 and MMP1 (OR = 2.44, 95% CI: 1.24, 4.81 with protein. Five GEIs were associated with survival at the 5% significance level but not after multiple testing adjustment: CXCR1 (HR = 2.06, 95% CI: 1.13, 3.75 with smoking; and KDR (HR = 4.36, 95% CI: 1.62, 11.73, TLR2 (HR = 9.06, 95% CI: 1.14, 72.11, EGR2 (HR = 2.45, 95% CI: 1.42, 4.22, and EGFR (HR = 6.33, 95% CI: 1.95, 20.54 with protein. GEIs between angiogenesis genes and smoking, alcohol, and animal protein impact rectal cancer risk. Our results support the importance of considering the biologic hypothesis to characterize GEIs associated with cancer outcomes.

  20. A Novel Truncated Form of Serum Amyloid A in Kawasaki Disease.

    Directory of Open Access Journals (Sweden)

    John C Whitin

    Full Text Available Kawasaki disease (KD is an acute vasculitis in children that can cause coronary artery abnormalities. Its diagnosis is challenging, and many cytokines, chemokines, acute phase reactants, and growth factors have failed evaluation as specific biomarkers to distinguish KD from other febrile illnesses. We performed protein profiling, comparing plasma from children with KD with febrile control (FC subjects to determine if there were specific proteins or peptides that could distinguish the two clinical states.Plasma from three independent cohorts from the blood of 68 KD and 61 FC subjects was fractionated by anion exchange chromatography, followed by surface-enhanced laser desorption ionization (SELDI mass spectrometry of the fractions. The mass spectra of KD and FC plasma samples were analyzed for peaks that were statistically significantly different.A mass spectrometry peak with a mass of 7,860 Da had high intensity in acute KD subjects compared to subacute KD (p = 0.0003 and FC (p = 7.9 x 10-10 subjects. We identified this peak as a novel truncated form of serum amyloid A with N-terminal at Lys-34 of the circulating form and validated its identity using a hybrid mass spectrum immunoassay technique. The truncated form of serum amyloid A was present in plasma of KD subjects when blood was collected in tubes containing protease inhibitors. This peak disappeared when the patients were examined after their symptoms resolved. Intensities of this peptide did not correlate with KD-associated laboratory values or with other mass spectrum peaks from the plasma of these KD subjects.Using SELDI mass spectrometry, we have discovered a novel truncated form of serum amyloid A that is elevated in the plasma of KD when compared with FC subjects. Future studies will evaluate its relevance as a diagnostic biomarker and its potential role in the pathophysiology of KD.

  1. A computational approach for fluid queues driven by truncated birth-death processes.

    NARCIS (Netherlands)

    Lenin, R.B.; Parthasarathy, P.R.

    2000-01-01

    In this paper, we analyze fluid queues driven by truncated birth-death processes with general birth and death rates. We compute the equilibrium distribution of the content of the fluid buffer by providing efficient numerical procedures to compute the eigenvalues and the eigenvectors of the

  2. Non-linear buckling of an FGM truncated conical shell surrounded by an elastic medium

    International Nuclear Information System (INIS)

    Sofiyev, A.H.; Kuruoglu, N.

    2013-01-01

    In this paper, the non-linear buckling of the truncated conical shell made of functionally graded materials (FGMs) surrounded by an elastic medium has been studied using the large deformation theory with von Karman–Donnell-type of kinematic non-linearity. A two-parameter foundation model (Pasternak-type) is used to describe the shell–foundation interaction. The FGM properties are assumed to vary continuously through the thickness direction. The fundamental relations, the modified Donnell type non-linear stability and compatibility equations of the FGM truncated conical shell resting on the Pasternak-type elastic foundation are derived. By using the Superposition and Galerkin methods, the non-linear stability equations for the FGM truncated conical shell is solved. Finally, influences of variations of Winkler foundation stiffness and shear subgrade modulus of the foundation, compositional profiles and shell characteristics on the dimensionless critical non-linear axial load are investigated. The present results are compared with the available data for a special case. -- Highlights: • Nonlinear buckling of FGM conical shell surrounded by elastic medium is studied. • Pasternak foundation model is used to describe the shell–foundation interaction. • Nonlinear basic equations are derived. • Problem is solved by using Superposition and Galerkin methods. • Influences of various parameters on the nonlinear critical load are investigated

  3. Sexual selection, genetic conflict, selfish genes, and the atypical patterns of gene expression in spermatogenic cells.

    Science.gov (United States)

    Kleene, Kenneth C

    2005-01-01

    This review proposes that the peculiar patterns of gene expression in spermatogenic cells are the consequence of powerful evolutionary forces known as sexual selection. Sexual selection is generally characterized by intense competition of males for females, an enormous variety of the strategies to maximize male reproductive success, exaggerated male traits at all levels of biological organization, co-evolution of sexual traits in males and females, and conflict between the sexual advantage of the male trait and the reproductive fitness of females and the individual fitness of both sexes. In addition, spermatogenesis is afflicted by selfish genes that promote their transmission to progeny while causing deleterious effects. Sexual selection, selfish genes, and genetic conflict provide compelling explanations for many atypical features of gene expression in spermatogenic cells including the gross overexpression of certain mRNAs, transcripts encoding truncated proteins that cannot carry out basic functions of the proteins encoded by the same genes in somatic cells, the large number of gene families containing paralogous genes encoding spermatogenic cell-specific isoforms, the large number of testis-cancer-associated genes that are expressed only in spermatogenic cells and malignant cells, and the overbearing role of Sertoli cells in regulating the number and quality of spermatozoa.

  4. Chaos and noise in a truncated Toda potential

    International Nuclear Information System (INIS)

    Habib, S.; Kandrup, H.E.; Mahon, M.E.

    1996-01-01

    Results are reported from a numerical investigation of orbits in a truncated Toda potential that is perturbed by weak friction and noise. Aside from the perturbations displaying a simple scaling in the amplitude of the friction and noise, it is found that even very weak friction and noise can induce an extrinsic diffusion through cantori on a time scale that is much shorter than that associated with intrinsic diffusion in the unperturbed system. The results have applications in galactic dynamics and in the formation of a beam halo in charged particle beams. copyright 1996 The American Physical Society

  5. Sindbis Virus-Pseudotyped Lentiviral Vectors Carrying VEGFR2-Specific Nanobody for Potential Transductional Targeting of Tumor Vasculature.

    Science.gov (United States)

    Ahani, Roshank; Roohvand, Farzin; Cohan, Reza Ahangari; Etemadzadeh, Mohammad Hossein; Mohajel, Nasir; Behdani, Mahdi; Shahosseini, Zahra; Madani, Navid; Azadmanesh, Kayhan

    2016-11-01

    Introduction of selectivity/specificity into viral-based gene delivery systems, such as lentiviral vectors (LVs), is crucial in their systemic administration for cancer gene therapy. The pivotal role of tumor-associated endothelial cells (TAECs) in tumor angiogenesis and overexpression of vascular endothelial growth factor receptor-2 (VEGFR2 or KDR) in TAECs makes them a potent target in cancer treatment. Herein, we report the development of VEGFR2-targeted LVs pseudotyped with chimeric sindbis virus E2 glycoprotein (cSVE2s). For this purpose, either sequence of a VEGFR2-specific nanobody or its natural ligand (VEGF 121 ) was inserted into the binding site of sindbis virus E2 glycoprotein. In silico modeling data suggested that the inserted targeting motifs were exposed in the context of cSVE2s. Western blot analysis of LVs indicated the incorporation of cSVE2s into viral particles. Capture ELISA demonstrated the specificity/functionality of the incorporated cSVE2s. Transduction of 293/KDR (expressing VEGFR2) or 293T cells (negative control) by constructed LVs followed by fluorescent microscopy and flow cytometric analyses indicated selective transduction of 293/KDR cells (30 %) by both targeting motifs compared to 293T control cells (1-2 %). These results implied similar targeting properties of VEGFR2-specific nanobody compared to the VEGF 121 and indicated the potential for transductional targeting of tumor vasculature by the nanobody displaying LVs.

  6. On the truncation of the azimuthal mode spectrum of high-order probes in probe-corrected spherical near-field antenna measurements

    DEFF Research Database (Denmark)

    Pivnenko, Sergey; Laitinen, Tommi

    2011-01-01

    Azimuthal mode (m mode) truncation of a high-order probe pattern in probe-corrected spherical near-field antenna measurements is studied in this paper. The results of this paper provide rules for appropriate and sufficient m-mode truncation for non-ideal first-order probes and odd-order probes wi...

  7. Modified truncated randomized singular value decomposition (MTRSVD) algorithms for large scale discrete ill-posed problems with general-form regularization

    Science.gov (United States)

    Jia, Zhongxiao; Yang, Yanfei

    2018-05-01

    In this paper, we propose new randomization based algorithms for large scale linear discrete ill-posed problems with general-form regularization: subject to , where L is a regularization matrix. Our algorithms are inspired by the modified truncated singular value decomposition (MTSVD) method, which suits only for small to medium scale problems, and randomized SVD (RSVD) algorithms that generate good low rank approximations to A. We use rank-k truncated randomized SVD (TRSVD) approximations to A by truncating the rank- RSVD approximations to A, where q is an oversampling parameter. The resulting algorithms are called modified TRSVD (MTRSVD) methods. At every step, we use the LSQR algorithm to solve the resulting inner least squares problem, which is proved to become better conditioned as k increases so that LSQR converges faster. We present sharp bounds for the approximation accuracy of the RSVDs and TRSVDs for severely, moderately and mildly ill-posed problems, and substantially improve a known basic bound for TRSVD approximations. We prove how to choose the stopping tolerance for LSQR in order to guarantee that the computed and exact best regularized solutions have the same accuracy. Numerical experiments illustrate that the best regularized solutions by MTRSVD are as accurate as the ones by the truncated generalized singular value decomposition (TGSVD) algorithm, and at least as accurate as those by some existing truncated randomized generalized singular value decomposition (TRGSVD) algorithms. This work was supported in part by the National Science Foundation of China (Nos. 11771249 and 11371219).

  8. Virtues and limitations of the truncated Holstein–Primakoff description of quantum rotors

    International Nuclear Information System (INIS)

    Hirsch, Jorge G; Castaños, Octavio; López-Peña, Ramón; Nahmad-Achar, Eduardo

    2013-01-01

    A Hamiltonian describing the collective behaviour of N interacting spins can be mapped to a bosonic one employing the Holstein–Primakoff realization, at the expense of having an infinite series in powers of the boson creation and annihilation operators. Truncating this series up to quadratic terms allows obtaining analytic solutions through a Bogoliubov transformation, which becomes exact in the limit N → ∞. The Hamiltonian exhibits a phase transition from single-spin excitations to a collective mode. In the vicinity of this phase transition, the truncated solutions predict the existence of singularities for a finite number of spins, which have no counterpart in the exact diagonalization. Renormalization allows to extract from these divergences the exact behaviour of relevant observables with the number of spins around the phase transition, and to relate it with the class of universality to which the model belongs. In this work a detailed analysis of these aspects is presented for the Lipkin model. (comment)

  9. Heterozygous RFX6 protein truncating variants are associated with MODY with reduced penetrance.

    Science.gov (United States)

    Patel, Kashyap A; Kettunen, Jarno; Laakso, Markku; Stančáková, Alena; Laver, Thomas W; Colclough, Kevin; Johnson, Matthew B; Abramowicz, Marc; Groop, Leif; Miettinen, Päivi J; Shepherd, Maggie H; Flanagan, Sarah E; Ellard, Sian; Inagaki, Nobuya; Hattersley, Andrew T; Tuomi, Tiinamaija; Cnop, Miriam; Weedon, Michael N

    2017-10-12

    Finding new causes of monogenic diabetes helps understand glycaemic regulation in humans. To find novel genetic causes of maturity-onset diabetes of the young (MODY), we sequenced MODY cases with unknown aetiology and compared variant frequencies to large public databases. From 36 European patients, we identify two probands with novel RFX6 heterozygous nonsense variants. RFX6 protein truncating variants are enriched in the MODY discovery cohort compared to the European control population within ExAC (odds ratio = 131, P = 1 × 10 -4 ). We find similar results in non-Finnish European (n = 348, odds ratio = 43, P = 5 × 10 -5 ) and Finnish (n = 80, odds ratio = 22, P = 1 × 10 -6 ) replication cohorts. RFX6 heterozygotes have reduced penetrance of diabetes compared to common HNF1A and HNF4A-MODY mutations (27, 70 and 55% at 25 years of age, respectively). The hyperglycaemia results from beta-cell dysfunction and is associated with lower fasting and stimulated gastric inhibitory polypeptide (GIP) levels. Our study demonstrates that heterozygous RFX6 protein truncating variants are associated with MODY with reduced penetrance.Maturity-onset diabetes of the young (MODY) is the most common subtype of familial diabetes. Here, Patel et al. use targeted DNA sequencing of MODY patients and large-scale publically available data to show that RFX6 heterozygous protein truncating variants cause reduced penetrance MODY.

  10. A truncated conical beam model for analysis of the vibration of rat whiskers.

    Science.gov (United States)

    Yan, Wenyi; Kan, Qianhua; Kergrene, Kenan; Kang, Guozheng; Feng, Xi-Qiao; Rajan, Ramesh

    2013-08-09

    A truncated conical beam model is developed to study the vibration behaviour of a rat whisker. Translational and rotational springs are introduced to better represent the constraint conditions at the base of the whiskers in a living rat. Dimensional analysis shows that the natural frequency of a truncated conical beam with generic spring constraints at its ends is inversely proportional to the square root of the mass density. Under all the combinations of the classical free, pinned, sliding or fixed boundary conditions of a truncated conical beam, it is proved that the natural frequency can be expressed as f = α(rb/L(2))E/ρ and the frequency coefficient α only depends on the ratio of the radii at the two ends of the beam. The natural frequencies of a representative rat whisker are predicted for two typical situations: freely whisking in air and the tip touching an object. Our numerical results show that there exists a window where the natural frequencies of a rat whisker are very sensitive to the change of the rotational constraint at the base. This finding is also confirmed by the numerical results of 18 whiskers with their data available from literature. It can be concluded that the natural frequencies of a rat whisker can be adjusted within a wide range through manipulating the constraints of the follicle on the rat base by a behaving animal. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Aspergillus flavus aswA, a gene homolog of Aspergillus nidulans oefC, regulates sclerotial development and biosynthesis of sclerotium-associated secondary metabolites

    Science.gov (United States)

    Aspergillus flavus aswA (AFLA_085170) is a gene encoding a Zn(II)2Cys6 DNA-binding domain. Partial deletion of aswA yielded strains that made a truncated gene transcript and generated a fungus that produced a greatly increased number of sclerotia. These sclerotia were odd-shaped and non-pigmented (w...

  12. Expression and characterization of a novel truncated rotavirus VP4 for the development of a recombinant rotavirus vaccine.

    Science.gov (United States)

    Li, Yijian; Xue, Miaoge; Yu, Linqi; Luo, Guoxing; Yang, Han; Jia, Lianzhi; Zeng, Yuanjun; Li, Tingdong; Ge, Shengxiang; Xia, Ningshao

    2018-04-12

    The outer capsid protein VP4 is an important target for the development of a recombinant rotavirus vaccine because it mediates the attachment and penetration of rotavirus. Due to the poor solubility of full-length VP4, VP8 was explored as candidate rotavirus vaccines in the past years. In previous studies, it has been found that the N-terminal truncated VP8 protein, VP8-1 (aa26-231), could be expressed in soluble form with improved immunogenicity compared to the core of VP8 (aa65-223). However, this protein stimulated only a weak immune response when aluminum hydroxide was used as an adjuvant. In addition, it should be noted that the protective efficacy of VP4 was higher than that of VP8 and VP5. In this study, it was found that when the N-terminal 25 amino acids were deleted, the truncated VP4 ∗ (aa26-476) containing VP8 and the stalk domain of VP5 could be expressed in soluble form in E. coli and purified to homogeneous trimers. Furthermore, the truncated VP4 could induce high titers of neutralizing antibodies when aluminum adjuvant was used and conferred high protective efficacy in reducing the severity of diarrhea and rotavirus shedding in stools in animal models. The immunogenicity of the truncated VP4 was significantly higher than that of VP8 ∗ and VP5 ∗ alone. Taken together, the truncated VP4 ∗ (aa26-476), with enhanced immunogenicity and immunoprotectivity, could be considered as a viable candidate for further development and has the potential to become a parenterally administered rotavirus vaccine. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. Identification and purification of truncated insulin-like growth factor I from porcine uterus. Evidence for high biological potency

    International Nuclear Information System (INIS)

    Ogasawara, M.; Karey, K.P.; Marquardt, H.; Sirbasku, D.A.

    1989-01-01

    The authors report the completion of the purification of uterine-derived growth factors (UDGF) described previously by this laboratory. During isolation, the mitogenic activity was monitored by using the human MCF-7 breast cancer cells in serum-free Ham's F12 and Dulbecco's modified Eagle's medium (1:1, v/v) containing 15 mM 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid, 200 μg/mL bovine serum albumin, and 10 μg/mL human transferrin. This medium sustained growth for several days in response to a single addition of growth factor. The mitogens were shown by protein microsequencing to be DES 1 → 3 to DES 1 → 6 forms of insulin-like growth factor I (truncated IGF-I). An M r estimated by 125 I labeling, urea-sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and autoradiography was consistent with a DES 1 → 3(4) N α truncation. Immunoadsorption and radioimmunoassay confirmed immunological properties equivalent to IGF-I. Radioreceptor assays showed truncated IGF-I was functionally equivalent to recombinant IGF-I. They conclude that the major acid-stable low-M r mitogenic activities isolated from uterus are very potent forms of truncated IGF-I capable of stimulating growth of epithelial and mesenchymal cells

  14. Tumoral Environment Triggers Transcript Anomalies in Established Tumors: Induction of Altered Gene Expression and of Aberrant, Truncated and B2 Repeat-Containing Gene Transcripts

    Directory of Open Access Journals (Sweden)

    Pieter Rottiers

    1999-12-01

    Full Text Available In addition to eugenetic changes, cancerous cells exhibit extensive modifications in the expression levels of a variety of genes. The phenotypic switch observed after inoculation of T lymphoma cells into syngenic mice illustrates the active participation of tumoral environment in the induction of an aberrant gene expression pattern. To further substantiate this contribution, we performed polymerase chain reaction (PCR-based subtraction suppression hybridization (SSH to identify genes that are differentially expressed in tumor-derived EL4/13.3 cells compared to the same cells isolated from cultures. Besides a number of unknown genes, the subtracted library contained several known genes that have been reported to be expressed at increased levels in tumors and/or to contribute to carcinogenesis. Apart from clones representing translated transcripts, the subtracted library also contained a high number of clones representing B2 repeat elements, viz. short interspersed repetitive elements that are transcribed by RNA polymerase III. Northern blotting confirmed the induction of B2 transcripts in tumor tissue and also revealed induction of chimeric, B2 repeat-containing mRNA. The appearance of chimeric transcripts was accompanied by aberrant, shorter-than-full-length transcripts, specifically from upregulated genes. Accordingly, in addition to altered gene expression, tumoral environmental triggers constitute a potent mechanism to create an epigenetic diversity in cancers by inducing extensive transcript anomalies.

  15. Use of the negative binomial-truncated Poisson distribution in thunderstorm prediction

    Science.gov (United States)

    Cohen, A. C.

    1971-01-01

    A probability model is presented for the distribution of thunderstorms over a small area given that thunderstorm events (1 or more thunderstorms) are occurring over a larger area. The model incorporates the negative binomial and truncated Poisson distributions. Probability tables for Cape Kennedy for spring, summer, and fall months and seasons are presented. The computer program used to compute these probabilities is appended.

  16. Elimination of the truncated message from the herpes simplex virus thymidine kinase suicide gene

    NARCIS (Netherlands)

    Chalmers, D; Ferrand, C; Apperley, JF; Melo, JV; Ebeling, S; Newton, [No Value; Duperrier, A; Hagenbeek, A; Garrett, E; Tiberghien, P; Garin, M

    Introduction of the Herpes simplex virus thymidine kinase (HSV-tk) gene into target cells renders them susceptible to killing by ganciclovir (GCV). We are studying the use of HSV-tk-transduced T lymphocytes in the context of hematopoietic stem cell transplantation. We have previously shown, in vitro

  17. Differential isotope dansylation labeling combined with liquid chromatography mass spectrometry for quantification of intact and N-terminal truncated proteins

    International Nuclear Information System (INIS)

    Tang, Yanan; Li, Liang

    2013-01-01

    Graphical abstract: -- Highlights: •LC–MS was developed for quantifying protein mixtures containing both intact and N-terminal truncated proteins. • 12 C 2 -Dansylation of the N-terminal amino acid of proteins was done first, followed by microwave-assisted acid hydrolysis. •The released 12 C 2 -dansyl labeled N-terminal amino acid was quantified using 13 C 2 -dansyl labeled amino acid standards. •The method provided accurate and precise results for quantifying intact and N-terminal truncated proteins within 8 h. -- Abstract: The N-terminal amino acids of proteins are important structure units for maintaining the biological function, localization, and interaction networks of proteins. Under different biological conditions, one or several N-terminal amino acids could be cleaved from an intact protein due to processes, such as proteolysis, resulting in the change of protein properties. Thus, the ability to quantify the N-terminal truncated forms of proteins is of great importance, particularly in the area of development and production of protein-based drugs where the relative quantity of the intact protein and its truncated form needs to be monitored. In this work, we describe a rapid method for absolute quantification of protein mixtures containing intact and N-terminal truncated proteins. This method is based on dansylation labeling of the N-terminal amino acids of proteins, followed by microwave-assisted acid hydrolysis of the proteins into amino acids. It is shown that dansyl labeled amino acids are stable in acidic conditions and can be quantified by liquid chromatography mass spectrometry (LC–MS) with the use of isotope analog standards

  18. Field of view extension and truncation correction for MR-based human attenuation correction in simultaneous MR/PET imaging

    International Nuclear Information System (INIS)

    Blumhagen, Jan O.; Ladebeck, Ralf; Fenchel, Matthias; Braun, Harald; Quick, Harald H.; Faul, David; Scheffler, Klaus

    2014-01-01

    Purpose: In quantitative PET imaging, it is critical to accurately measure and compensate for the attenuation of the photons absorbed in the tissue. While in PET/CT the linear attenuation coefficients can be easily determined from a low-dose CT-based transmission scan, in whole-body MR/PET the computation of the linear attenuation coefficients is based on the MR data. However, a constraint of the MR-based attenuation correction (AC) is the MR-inherent field-of-view (FoV) limitation due to static magnetic field (B 0 ) inhomogeneities and gradient nonlinearities. Therefore, the MR-based human AC map may be truncated or geometrically distorted toward the edges of the FoV and, consequently, the PET reconstruction with MR-based AC may be biased. This is especially of impact laterally where the patient arms rest beside the body and are not fully considered. Methods: A method is proposed to extend the MR FoV by determining an optimal readout gradient field which locally compensates B 0 inhomogeneities and gradient nonlinearities. This technique was used to reduce truncation in AC maps of 12 patients, and the impact on the PET quantification was analyzed and compared to truncated data without applying the FoV extension and additionally to an established approach of PET-based FoV extension. Results: The truncation artifacts in the MR-based AC maps were successfully reduced in all patients, and the mean body volume was thereby increased by 5.4%. In some cases large patient-dependent changes in SUV of up to 30% were observed in individual lesions when compared to the standard truncated attenuation map. Conclusions: The proposed technique successfully extends the MR FoV in MR-based attenuation correction and shows an improvement of PET quantification in whole-body MR/PET hybrid imaging. In comparison to the PET-based completion of the truncated body contour, the proposed method is also applicable to specialized PET tracers with little uptake in the arms and might reduce the

  19. Quark-gluon vertex dressing and meson masses beyond ladder-rainbow truncation

    International Nuclear Information System (INIS)

    Matevosyan, Hrayr H.; Thomas, Anthony W.; Tandy, Peter C.

    2007-01-01

    We include a generalized infinite class of quark-gluon vertex dressing diagrams in a study of how dynamics beyond the ladder-rainbow truncation influences the Bethe-Salpeter description of light-quark pseudoscalar and vector mesons. The diagrammatic specification of the vertex is mapped into a corresponding specification of the Bethe-Salpeter kernel, which preserves chiral symmetry. This study adopts the algebraic format afforded by the simple interaction kernel used in previous work on this topic. The new feature of the present work is that in every diagram summed for the vertex and the corresponding Bethe-Salpeter kernel, each quark-gluon vertex is required to be the self-consistent vertex solution. We also adopt from previous work the effective accounting for the role of the explicitly non-Abelian three-gluon coupling in a global manner through one parameter determined from recent lattice-QCD data for the vertex. Within the current model, the more consistent dressed vertex limits the ladder-rainbow truncation error for vector mesons to be never more than 10% as the current quark mass is varied from the u/d region to the b region

  20. Truncating Homozygous Mutation of Carboxypeptidase E (CPE in a Morbidly Obese Female with Type 2 Diabetes Mellitus, Intellectual Disability and Hypogonadotrophic Hypogonadism.

    Directory of Open Access Journals (Sweden)

    Suzanne I M Alsters

    Full Text Available Carboxypeptidase E is a peptide processing enzyme, involved in cleaving numerous peptide precursors, including neuropeptides and hormones involved in appetite control and glucose metabolism. Exome sequencing of a morbidly obese female from a consanguineous family revealed homozygosity for a truncating mutation of the CPE gene (c.76_98del; p.E26RfsX68. Analysis detected no CPE expression in whole blood-derived RNA from the proband, consistent with nonsense-mediated decay. The morbid obesity, intellectual disability, abnormal glucose homeostasis and hypogonadotrophic hypogonadism seen in this individual recapitulates phenotypes in the previously described fat/fat and Cpe knockout mouse models, evidencing the importance of this peptide/hormone-processing enzyme in regulating body weight, metabolism, and brain and reproductive function in humans.

  1. Subclinical Pregnancy Toxemia-Induced Gene Expression Changes in Ovine Placenta and Uterus.

    Science.gov (United States)

    Kasimanickam, Ramanathan K

    2016-01-01

    The objective was to elucidate gene expression differences in uterus, caruncle, and cotyledon of ewes with subclinical pregnancy toxemia (SCPT) and healthy ewes, and to identify associated biological functions and pathways involved in pregnancy toxemia. On Day 136 (±1 day) post-breeding, ewes (n = 18) had body condition score (BCS; 1-5; 1, emaciated; 5, obese) assessed, and blood samples were collected for plasma glucose and β-hydroxybutyrate (BHBA) analyses. The ewes were euthanized, and tissue samples were collected from the gravid uterus and placentomes. Based on BCS (2.0 ± 0.02), glucose (2.4 ± 0.33), and BHBA (0.97 ± 0.06) concentrations, ewes (n = 10) were grouped as healthy (n = 5) and subclinical SCPT (n = 5) ewes. The mRNA expressions were determined by quantitative PCR method, and prediction of miRNA partners and target genes for the predicted miRNA were identified using miRDB (http://mirdb.org/miRDB/). Top ranked target genes were used to identify associated biological functions and pathways in response to SPCT using PANTHER. The angiogenesis genes VEGF and PlGF, and AdipoQ, AdipoR2, PPARG, LEP, IGF1, IGF2, IL1b, and TNFα mRNA expressions were lower in abundances, whereas hypoxia genes eNOS, HIF1a, and HIF 2a, and sFlt1 and KDR mRNA expressions were greater in abundances in uterus and placenta of SCPT ewes compared to healthy ewes (P influence placental vascular development and angiogenesis as noted in this study set the course for hemodynamic changes and hence have a major impact on the rate of transplacental nutrient exchange, fetal growth, and health of the dam.

  2. Truncated exponential-rigid-rotor model for strong electron and ion rings

    International Nuclear Information System (INIS)

    Larrabee, D.A.; Lovelace, R.V.; Fleischmann, H.H.

    1979-01-01

    A comprehensive study of exponential-rigid-rotor equilibria for strong electron and ion rings indicates the presence of a sizeable percentage of untrapped particles in all equilibria with aspect-ratios R/a approximately <4. Such aspect-ratios are required in fusion-relevant rings. Significant changes in the equilibria are observed when untrapped particles are excluded by the use of a truncated exponential-rigid-rotor distribution function. (author)

  3. Neurodevelopmental disorders associated with dosage imbalance of ZBTB20 correlate with the morbidity spectrum of ZBTB20 candidate target genes

    DEFF Research Database (Denmark)

    Rasmussen, Malene B; Nielsen, Jakob V; Lourenço, Charles M

    2014-01-01

    (SRO) involved five RefSeq genes, including the transcription factor gene ZBTB20 and the dopamine receptor gene DRD3, considered as candidate genes for the syndrome. METHODS AND RESULTS: We used array comparative genomic hybridization and next-generation mate-pair sequencing to identify key structural...... patient with developmental delay and autism, we detected the first microdeletion at 3q13.31, which truncated ZBTB20 but did not involve DRD3 or the other genes within the previously defined SRO. Zbtb20 directly represses 346 genes in the developing murine brain. Of the 342 human orthologous ZBTB20...

  4. Integral equation solution for truncated slab structures by using a fringe current formulation

    DEFF Research Database (Denmark)

    Jørgensen, Erik; Toccafondi, A.; Maci, S.

    1999-01-01

    Full-wave solutions of truncated dielectric slab problems are interesting for a variety of engineering applications, in particular patch antennas on finite ground planes. For this application a canonical reference solution is that of a semi-infinite slab illuminated by a line source. Standard int...

  5. The renormalized Hamiltonian truncation method in the large E{sub T} expansion

    Energy Technology Data Exchange (ETDEWEB)

    Elias-Miró, J. [SISSA and INFN, I-34136 Trieste (Italy); Montull, M. [Institut de Física d’Altes Energies (IFAE), Barcelona Institute of Science and Technology (BIST), Campus UAB, E-08193 Bellaterra (Spain); Riembau, M. [Institut de Física d’Altes Energies (IFAE), Barcelona Institute of Science and Technology (BIST), Campus UAB, E-08193 Bellaterra (Spain); DESY, Notkestrasse 85, 22607 Hamburg (Germany)

    2016-04-22

    Hamiltonian Truncation Methods are a useful numerical tool to study strongly coupled QFTs. In this work we present a new method to compute the exact corrections, at any order, in the Hamiltonian Truncation approach presented by Rychkov et al. in refs. http://dx.doi.org/10.1103/PhysRevD.91.085011; http://dx.doi.org/10.1103/PhysRevD.93.065014; http://dx.doi.org/10.1103/PhysRevD.91.025005. The method is general but as an example we calculate the exact g{sup 2} and some of the g{sup 3} contributions for the ϕ{sup 4} theory in two dimensions. The coefficients of the local expansion calculated in ref. http://dx.doi.org/10.1103/PhysRevD.91.085011 are shown to be given by phase space integrals. In addition we find new approximations to speed up the numerical calculations and implement them to compute the lowest energy levels at strong coupling. A simple diagrammatic representation of the corrections and various tests are also introduced.

  6. PLK1 has tumor-suppressive potential in APC-truncated colon cancer cells.

    Science.gov (United States)

    Raab, Monika; Sanhaji, Mourad; Matthess, Yves; Hörlin, Albrecht; Lorenz, Ioana; Dötsch, Christina; Habbe, Nils; Waidmann, Oliver; Kurunci-Csacsko, Elisabeth; Firestein, Ron; Becker, Sven; Strebhardt, Klaus

    2018-03-16

    The spindle assembly checkpoint (SAC) acts as a molecular safeguard in ensuring faithful chromosome transmission during mitosis, which is regulated by a complex interplay between phosphatases and kinases including PLK1. Adenomatous polyposis coli (APC) germline mutations cause aneuploidy and are responsible for familial adenomatous polyposis (FAP). Here we study the role of PLK1 in colon cancer cells with chromosomal instability promoted by APC truncation (APC-ΔC). The expression of APC-ΔC in colon cells reduces the accumulation of mitotic cells upon PLK1 inhibition, accelerates mitotic exit and increases the survival of cells with enhanced chromosomal abnormalities. The inhibition of PLK1 in mitotic, APC-∆C-expressing cells reduces the kinetochore levels of Aurora B and hampers the recruitment of SAC component suggesting a compromised mitotic checkpoint. Furthermore, Plk1 inhibition (RNAi, pharmacological compounds) promotes the development of adenomatous polyps in two independent Apc Min/+ mouse models. High PLK1 expression increases the survival of colon cancer patients expressing a truncated APC significantly.

  7. Design Optimization for a Truncated Catenary Mooring System for Scale Model Test

    Directory of Open Access Journals (Sweden)

    Climent Molins

    2015-11-01

    Full Text Available One of the main aspects when testing floating offshore platforms is the scaled mooring system, particularly with the increased depths where such platforms are intended. The paper proposes the use of truncated mooring systems to emulate the real mooring system by solving an optimization problem. This approach could be an interesting option when the existing testing facilities do not have enough available space. As part of the development of a new spar platform made of concrete for Floating Offshore Wind Turbines (FOWTs, called Windcrete, a station keeping system with catenary shaped lines was selected. The test facility available for the planned experiments had an important width constraint. Then, an algorithm to optimize the design of the scaled truncated mooring system using different weights of lines was developed. The optimization process adjusts the quasi-static behavior of the scaled mooring system as much as possible to the real mooring system within its expected maximum displacement range, where the catenary line provides the restoring forces by its suspended line length.

  8. Expression of Truncated Neurokinin-1 Receptor in Childhood Neuroblastoma is Independent of Tumor Biology and Stage.

    Science.gov (United States)

    Pohl, Alexandra; Kappler, Roland; Mühling, Jakob; VON Schweinitz, Dietrich; Berger, Michael

    2017-11-01

    Neuroblastoma is an embryonal malignancy arising from the aberrant growth of neural crest progenitor cells of the sympathetic nervous system. The tachykinin receptor 1 (TACR1) - substance P complex is associated with tumoral angiogenesis and cell proliferation in a variety of cancer types. Inhibition of TACR1 was recently described to impede growth of NB cell lines. However, the relevance of TACR1 in clinical settings is unknown. We investigated gene expression levels of full-length and truncated TACR1 in 59 neuroblastomas and correlated these data with the patients' clinical parameters such as outcome, metastasis, International Neuroblastoma Staging System (INSS) status, MYCN proto-oncogene, bHLH transcription factor (MYCN) status, gender and age. Our results indicated that TACR1 is ubiquitously expressed in neuroblastoma but expression levels are independent of clinical parameters. Our data suggest that TACR1 might serve as a potent anticancer target in a large variety of patients with neuroblastoma, independent of tumor biology and clinical stage. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  9. Hamiltonian truncation approach to quenches in the Ising field theory

    Directory of Open Access Journals (Sweden)

    T. Rakovszky

    2016-10-01

    Full Text Available In contrast to lattice systems where powerful numerical techniques such as matrix product state based methods are available to study the non-equilibrium dynamics, the non-equilibrium behaviour of continuum systems is much harder to simulate. We demonstrate here that Hamiltonian truncation methods can be efficiently applied to this problem, by studying the quantum quench dynamics of the 1+1 dimensional Ising field theory using a truncated free fermionic space approach. After benchmarking the method with integrable quenches corresponding to changing the mass in a free Majorana fermion field theory, we study the effect of an integrability breaking perturbation by the longitudinal magnetic field. In both the ferromagnetic and paramagnetic phases of the model we find persistent oscillations with frequencies set by the low-lying particle excitations not only for small, but even for moderate size quenches. In the ferromagnetic phase these particles are the various non-perturbative confined bound states of the domain wall excitations, while in the paramagnetic phase the single magnon excitation governs the dynamics, allowing us to capture the time evolution of the magnetisation using a combination of known results from perturbation theory and form factor based methods. We point out that the dominance of low lying excitations allows for the numerical or experimental determination of the mass spectra through the study of the quench dynamics.

  10. Differential isotope dansylation labeling combined with liquid chromatography mass spectrometry for quantification of intact and N-terminal truncated proteins

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Yanan; Li, Liang, E-mail: Liang.Li@ualberta.ca

    2013-08-20

    Graphical abstract: -- Highlights: •LC–MS was developed for quantifying protein mixtures containing both intact and N-terminal truncated proteins. •{sup 12}C{sub 2}-Dansylation of the N-terminal amino acid of proteins was done first, followed by microwave-assisted acid hydrolysis. •The released {sup 12}C{sub 2}-dansyl labeled N-terminal amino acid was quantified using {sup 13}C{sub 2}-dansyl labeled amino acid standards. •The method provided accurate and precise results for quantifying intact and N-terminal truncated proteins within 8 h. -- Abstract: The N-terminal amino acids of proteins are important structure units for maintaining the biological function, localization, and interaction networks of proteins. Under different biological conditions, one or several N-terminal amino acids could be cleaved from an intact protein due to processes, such as proteolysis, resulting in the change of protein properties. Thus, the ability to quantify the N-terminal truncated forms of proteins is of great importance, particularly in the area of development and production of protein-based drugs where the relative quantity of the intact protein and its truncated form needs to be monitored. In this work, we describe a rapid method for absolute quantification of protein mixtures containing intact and N-terminal truncated proteins. This method is based on dansylation labeling of the N-terminal amino acids of proteins, followed by microwave-assisted acid hydrolysis of the proteins into amino acids. It is shown that dansyl labeled amino acids are stable in acidic conditions and can be quantified by liquid chromatography mass spectrometry (LC–MS) with the use of isotope analog standards.

  11. Increased frequency of FBN1 truncating and splicing variants in Marfan syndrome patients with aortic events.

    Science.gov (United States)

    Baudhuin, Linnea M; Kotzer, Katrina E; Lagerstedt, Susan A

    2015-03-01

    Marfan syndrome is a systemic disorder that typically involves FBN1 mutations and cardiovascular manifestations. We investigated FBN1 genotype-phenotype correlations with aortic events (aortic dissection and prophylactic aortic surgery) in patients with Marfan syndrome. Genotype and phenotype information from probands (n = 179) with an FBN1 pathogenic or likely pathogenic variant were assessed. A higher frequency of truncating or splicing FBN1 variants was observed in Ghent criteria-positive patients with an aortic event (n = 34) as compared with all other probands (n = 145) without a reported aortic event (79 vs. 39%; P Marfan syndrome patients with FBN1 truncating and splicing variants.Genet Med 17 3, 177-187.

  12. Defective angiogenesis delays thrombus resolution: a potential pathogenetic mechanism underlying chronic thromboembolic pulmonary hypertension

    Science.gov (United States)

    Panzenboeck, Adelheid; Winter, Max P; Schubert, Uwe; Voswinckel, Robert; Frey, Maria K; Jakowitsch, Johannes; Alimohammadi, Arman; Hobohm, Lukas; Mangold, Andreas; Bergmeister, Helga; Sibilia, Maria; Wagner, Erwin F; Mayer, Eckhard; Klepetko, Walter; Hoelzenbein, Thomas J; Preissner, Klaus T; Lang, Irene M

    2015-01-01

    Objective Restoration of patency is a natural target of vascular remodeling following venous thrombosis that involves vascular endothelial cells and smooth muscle cells as well as leukocytes. Acute pulmonary emboli usually resolve within six months. However, in some instances, thrombi transform into fibrous vascular obstructions, resulting in occlusion of the deep veins, or in chronic thromboembolic pulmonary hypertension (CTEPH). We proposed that dysregulated thrombus angiogenesis may contribute to thrombus persistence. Approach and Results Mice with an endothelial-cell-specific conditional deletion of vascular endothelial growth factor receptor 2/kinase insert domain protein receptor (VEGF-R2/Kdr) were utilized in a model of stagnant flow venous thrombosis closely resembling human deep vein thrombosis. Biochemical and functional analyses were performed on pulmonary endarterectomy specimens from patients with CTEPH, a human model of non-resolving venous thromboembolism. Endothelial cell-specific deletion of Kdr and subsequent ablation of thrombus vascularization delayed thrombus resolution. In accordance with these findings, organized human CTEPH thrombi were largely devoid of vascular structures. Several vessel-specific genes such as KDR, vascular endothelial cadherin and podoplanin were expressed at lower levels in white CTEPH thrombi than in organizing deep vein thrombi and organizing thrombi from aortic aneurysms. In addition, red CTEPH thrombi attenuated the angiogenic response induced by VEGF. Conclusions In the present work, we propose a mechanism of thrombus non-resolution demonstrating that endothelial cell-specific deletion of Kdr abates thrombus vessel formation, misguiding thrombus resolution. Medical conditions associated with the development of CTEPH may be compromising early thrombus angiogenesis. PMID:24526692

  13. Doubly truncated FosB isoform (Delta2DeltaFosB) induces osteosclerosis in transgenic mice and modulates expression and phosphorylation of Smads in osteoblasts independent of intrinsic AP-1 activity

    DEFF Research Database (Denmark)

    Sabatakos, George; Rowe, Glenn C; Kveiborg, Marie

    2008-01-01

    DeltaFosB and a further truncated isoform (Delta2DeltaFosB) that lacks known transactivation domains but, like DeltaFosB, induces increased expression of osteoblast marker genes. MATERIALS AND METHODS: To test Delta2DeltaFosB's ability to induce bone formation in vivo, we generated transgenic mice......6 expression. CONCLUSIONS: DeltaFosB's AP-1 transactivating function is not needed to induce increased bone formation, and Delta2DeltaFosB may act, at least in part, by increasing Smad1 expression, phosphorylation, and translocation to the nucleus....

  14. Knockdown resistance, Rdl alleles, and the annual entomological Inoculation rate of wild mosquito populations from Lower Moshi, Northern Tanzania

    Directory of Open Access Journals (Sweden)

    Aneth M Mahande

    2012-01-01

    Full Text Available Aim: Understanding vector behavioral response due to ecological factors is important in the control of disease vectors. This study was conducted to determine the knockdown resistance (kdr alleles, dieldrin resistance alleles, and entomological inoculation rates (EIRs of malaria vectors in lower Moshi irrigation schemes for the mitigation of disease transmission. Materials and Methods: The study was longitudinal design conducted for 14 months. Mosquitoes were collected fortnightly by using a CDC miniature light trap in 20 houses. Mosquitoes were identified morphologically in the field, of which 10% of this population was identified to species level by using molecular techniques. Samples from this study population were taken for kdr and resistance to dieldrin (rdl genes detection. Results: A total of 6220 mosquitoes were collected by using a light trap, of which 86.0% (n=5350 were Anopheles gambiae sensu lato and 14.0% (n=870 were Culex quinquefasciatus. Ten percent of the An. gambiae s.l. (n=535 collected were taken for species identification, of which 99.8% (n=534 were identified as An. arabiensis while 0.2% (n=1 were An. gambiae sensu stricto. Of the selected mosquitoes, 3.5% (n=19 were sporozoite positive. None of the mosquitoes tested had the kdr gene. The rdl resistant allele was detected at a frequency of 0.48 throughout the year. EIR was determined to be 0.54 ib/trap/year. Conclusion: The findings of this study suggest that the homozygous and the heterozygous resistance present in rdl genes demonstrated the effect of pesticide residues on resistance selection pressure in mosquitoes. A better insecticide usage protocol needs to be developed for farmers to use in order to avoid excessive use of pesticides. Key words: An. arabiensis, EIR, Knockdown mutation, Moshi, rdl locus, Tanzania

  15. Three-dimensional free vibration of functionally graded truncated conical shells subjected to thermal environment

    Energy Technology Data Exchange (ETDEWEB)

    Malekzadeh, P., E-mail: p_malekz@yahoo.com [Department of Mechanical Engineering, Persian Gulf University, Bushehr 75168 (Iran, Islamic Republic of); Fiouz, A.R.; Sobhrouyan, M. [Department of Civil Engineering, Persian Gulf University, Bushehr 75168 (Iran, Islamic Republic of)

    2012-01-15

    A three-dimensional (3D) free vibration analysis of the functionally graded (FG) truncated conical shells subjected to thermal environment is presented. The material properties are assumed to be temperature-dependent and graded in the radius direction, which can vary according to a simple power law distribution. The initial thermal stresses are obtained accurately by solving the thermoelastic equilibrium equations and by considering the two-dimensional axisymmetric temperature distribution in the shell. The differential quadrature method (DQM) as an efficient and accurate numerical tool is adopted to solve the thermal and thermo-mechanical governing equations. For this purpose, a mapping technique is employed to transform the cross section of the shell into the computational domain of DQM. The convergence behavior of the method is numerically demonstrated and comparison studies with the available solutions in the literature are performed. The effects of temperature dependence of material properties, geometrical parameters, material graded index, thermal and mechanical boundary conditions on the frequency parameters of the FG truncated conical shells are carried out. - Highlights: Black-Right-Pointing-Pointer 3D free vibration analysis of the functionally graded truncated conical shells is presented. Black-Right-Pointing-Pointer Two-dimensional axisymmetric temperature distribution in the shell is assumed. Black-Right-Pointing-Pointer The material properties are assumed to be temperature-dependent. Black-Right-Pointing-Pointer Initial thermal stresses due to thermal environment are evaluated accurately and included. Black-Right-Pointing-Pointer Representing the effects of different parameters on the non-dimensional frequencies.

  16. Correlations between chaos in a perturbed sine-Gordon equation and a truncated model system

    International Nuclear Information System (INIS)

    Bishop, A.R.; Flesch, R.; Forests, M.G.; Overman, E.A.

    1990-01-01

    The purpose of this paper is to present a first step toward providing coordinates and associated dynamics for low-dimensional attractors in nearly integrable partial differential equations (pdes), in particular, where the truncated system reflects salient geometric properties of the pde. This is achieved by correlating: (1) numerical results on the bifurcations to temporal chaos with spatial coherence of the damped, periodically forced sine-Gordon equation with periodic boundary conditions; (2) an interpretation of the spatial and temporal bifurcation structures of this perturbed integrable system with regard to the exact structure of the sine-Gordon phase space; (3) a model dynamical systems problem, which is itself a perturbed integrable Hamiltonian system, derived from the perturbed sine-Gordon equation by a finite mode Fourier truncation in the nonlinear Schroedinger limit; and (4) the bifurcations to chaos in the truncated phase space. In particular, a potential source of chaos in both the pde and the model ordinary differential equation systems is focused on: the existence of homoclinic orbits in the unperturbed integrable phase space and their continuation in the perturbed problem. The evidence presented here supports the thesis that the chaotic attractors of the weakly perturbed periodic sine-Gordon system consists of low-dimensional metastable attacking states together with intermediate states that are O(1) unstable and correspond to homoclinic states in the integrable phase space. It is surmised that the chaotic dynamics on these attractors is due to the perturbation of these homocline integrable configurations

  17. Tailor-made dimensions of diblock copolymer truncated micelles on a solid by UV irradiation.

    Science.gov (United States)

    Liou, Jiun-You; Sun, Ya-Sen

    2015-09-28

    We investigated the structural evolution of truncated micelles in ultrathin films of polystyrene-block-poly(2-vinylpyridine), PS-b-P2VP, of monolayer thickness on bare silicon substrates (SiOx/Si) upon UV irradiation in air- (UVIA) and nitrogen-rich (UVIN) environments. The structural evolution of micelles upon UV irradiation was monitored using GISAXS measurements in situ, while the surface morphology was probed using atomic force microscopy ex situ and the chemical composition using X-ray photoelectron spectroscopy (XPS). This work provides clear evidence for the interpretation of the relationship between the structural evolution and photochemical reactions in PS-b-P2VP truncated micelles upon UVIA and UVIN. Under UVIA treatment, photolysis and cross-linking reactions coexisted within the micelles; photolysis occurred mainly at the top of the micelles, whereas cross-linking occurred preferentially at the bottom. The shape and size of UVIA-treated truncated micelles were controlled predominantly by oxidative photolysis reactions, which depended on the concentration gradient of free radicals and oxygen along the micelle height. Because of an interplay between photolysis and photo-crosslinking, the scattering length densities (SLD) of PS and P2VP remained constant. In contrast, UVIN treatments enhanced the contrast in SLD between the PS shell and the P2VP core as cross-linking dominated over photolysis in the presence of nitrogen. The enhancement of the SLD contrast was due to the various degrees of cross-linking under UVIN for the PS and P2VP blocks.

  18. Zero-truncated panel Poisson mixture models: Estimating the impact on tourism benefits in Fukushima Prefecture.

    Science.gov (United States)

    Narukawa, Masaki; Nohara, Katsuhito

    2018-04-01

    This study proposes an estimation approach to panel count data, truncated at zero, in order to apply a contingent behavior travel cost method to revealed and stated preference data collected via a web-based survey. We develop zero-truncated panel Poisson mixture models by focusing on respondents who visited a site. In addition, we introduce an inverse Gaussian distribution to unobserved individual heterogeneity as an alternative to a popular gamma distribution, making it possible to capture effectively the long tail typically observed in trip data. We apply the proposed method to estimate the impact on tourism benefits in Fukushima Prefecture as a result of the Fukushima Nuclear Power Plant No. 1 accident. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. Non-perturbative methodologies for low-dimensional strongly-correlated systems: From non-Abelian bosonization to truncated spectrum methods.

    Science.gov (United States)

    James, Andrew J A; Konik, Robert M; Lecheminant, Philippe; Robinson, Neil J; Tsvelik, Alexei M

    2018-02-26

    We review two important non-perturbative approaches for extracting the physics of low-dimensional strongly correlated quantum systems. Firstly, we start by providing a comprehensive review of non-Abelian bosonization. This includes an introduction to the basic elements of conformal field theory as applied to systems with a current algebra, and we orient the reader by presenting a number of applications of non-Abelian bosonization to models with large symmetries. We then tie this technique into recent advances in the ability of cold atomic systems to realize complex symmetries. Secondly, we discuss truncated spectrum methods for the numerical study of systems in one and two dimensions. For one-dimensional systems we provide the reader with considerable insight into the methodology by reviewing canonical applications of the technique to the Ising model (and its variants) and the sine-Gordon model. Following this we review recent work on the development of renormalization groups, both numerical and analytical, that alleviate the effects of truncating the spectrum. Using these technologies, we consider a number of applications to one-dimensional systems: properties of carbon nanotubes, quenches in the Lieb-Liniger model, 1  +  1D quantum chromodynamics, as well as Landau-Ginzburg theories. In the final part we move our attention to consider truncated spectrum methods applied to two-dimensional systems. This involves combining truncated spectrum methods with matrix product state algorithms. We describe applications of this method to two-dimensional systems of free fermions and the quantum Ising model, including their non-equilibrium dynamics.

  20. Non-perturbative methodologies for low-dimensional strongly-correlated systems: From non-Abelian bosonization to truncated spectrum methods

    Science.gov (United States)

    James, Andrew J. A.; Konik, Robert M.; Lecheminant, Philippe; Robinson, Neil J.; Tsvelik, Alexei M.

    2018-04-01

    We review two important non-perturbative approaches for extracting the physics of low-dimensional strongly correlated quantum systems. Firstly, we start by providing a comprehensive review of non-Abelian bosonization. This includes an introduction to the basic elements of conformal field theory as applied to systems with a current algebra, and we orient the reader by presenting a number of applications of non-Abelian bosonization to models with large symmetries. We then tie this technique into recent advances in the ability of cold atomic systems to realize complex symmetries. Secondly, we discuss truncated spectrum methods for the numerical study of systems in one and two dimensions. For one-dimensional systems we provide the reader with considerable insight into the methodology by reviewing canonical applications of the technique to the Ising model (and its variants) and the sine-Gordon model. Following this we review recent work on the development of renormalization groups, both numerical and analytical, that alleviate the effects of truncating the spectrum. Using these technologies, we consider a number of applications to one-dimensional systems: properties of carbon nanotubes, quenches in the Lieb–Liniger model, 1  +  1D quantum chromodynamics, as well as Landau–Ginzburg theories. In the final part we move our attention to consider truncated spectrum methods applied to two-dimensional systems. This involves combining truncated spectrum methods with matrix product state algorithms. We describe applications of this method to two-dimensional systems of free fermions and the quantum Ising model, including their non-equilibrium dynamics.

  1. Exome sequencing identifies rare deleterious mutations in DNA repair genes FANCC and BLM as potential breast cancer susceptibility alleles.

    Directory of Open Access Journals (Sweden)

    Ella R Thompson

    2012-09-01

    Full Text Available Despite intensive efforts using linkage and candidate gene approaches, the genetic etiology for the majority of families with a multi-generational breast cancer predisposition is unknown. In this study, we used whole-exome sequencing of thirty-three individuals from 15 breast cancer families to identify potential predisposing genes. Our analysis identified families with heterozygous, deleterious mutations in the DNA repair genes FANCC and BLM, which are responsible for the autosomal recessive disorders Fanconi Anemia and Bloom syndrome. In total, screening of all exons in these genes in 438 breast cancer families identified three with truncating mutations in FANCC and two with truncating mutations in BLM. Additional screening of FANCC mutation hotspot exons identified one pathogenic mutation among an additional 957 breast cancer families. Importantly, none of the deleterious mutations were identified among 464 healthy controls and are not reported in the 1,000 Genomes data. Given the rarity of Fanconi Anemia and Bloom syndrome disorders among Caucasian populations, the finding of multiple deleterious mutations in these critical DNA repair genes among high-risk breast cancer families is intriguing and suggestive of a predisposing role. Our data demonstrate the utility of intra-family exome-sequencing approaches to uncover cancer predisposition genes, but highlight the major challenge of definitively validating candidates where the incidence of sporadic disease is high, germline mutations are not fully penetrant, and individual predisposition genes may only account for a tiny proportion of breast cancer families.

  2. Characterization of mTOR-Responsive Truncated mRNAs in Cell Proliferation

    Science.gov (United States)

    2017-07-01

    These findings identify a previously uncharacterized role for mTOR in modulating 3’- UTR length of mRNAs by alternative polyadenylation ( APA ). Another...outcome of APA in the mTOR-activated transcriptome is an early termination of mRNA transcription to produce truncated mRNAs with polyadenylation in...for exhaustive analysis of Alternative cleavage and polyadenylation ( APA ) events (Figure 1). In IntMAP, first the position of multiple

  3. Characterisation of a collagen gene subfamily from the potato cyst nematode Globodera pallida.

    Science.gov (United States)

    Gray, L J; Curtis, R H; Jones, J T

    2001-01-24

    We have isolated two full-length genomic DNA sequences, which encode the cuticle collagen proteins GP-COL-1 and GP-COL-2, from the potato cyst nematode Globodera pallida. A third, partial collagen gene ORF termed gp-col-t(t=truncated) has also been isolated and appears to represent an unexpressed pseudogene. The gp-col-1 and gp-col-2 genes both contain three short (nematode growth and reproduction. Immunochemical studies indicate that the GP-COL-1 protein is specifically located in the hypodermis of G. pallida adult females.

  4. Vaccination with DNA encoding truncated enterohemorrhagic Escherichia coli (EHEC factor for adherence-1 gene (efa-1’ confers protective immunity to mice infected with E. coli O157:H7

    Directory of Open Access Journals (Sweden)

    Roberto eRiquelme-Neira

    2016-01-01

    Full Text Available Enterohemorrhagic Escherichia coli (EHEC O157:H7 is the predominant causative agent of hemorrhagic colitis in humans and is the cause of haemolytic uraemic syndrome and other illnesses. Cattle have been implicated as the main reservoir of this organism. Here, we evaluated the immunogenicity and protective efficacy of a DNA vaccine encoding conserved sequences of truncated EHEC factor for adherence-1 (efa-1’ in a mouse model. Intranasal administration of plasmid DNA carrying the efa-1’ gene (pVAXefa-1’ into C57BL/6 mice elicited both humoral and cellular immune responses. In animals immunized with pVAXefa-1`, EHEC-secreted protein-specific IgM and IgG antibodies were detected in sera at day 45. Anti-EHEC-secreted protein sIgA was also detected in nasal and bronchoalveolar lavages. In addition, antigen-specific T-cell-proliferation, IL-10 and IFN-γ were observed upon re-stimulation with either heat-killed bacteria or EHEC-secreted proteins. Vaccinated animals were also protected against challenge with E. coli O157:H7 strain EDL933. These results suggest that DNA vaccine encoding efa-1´ have therapeutic potential in interventions against EHEC infections. This approach could lead to a new strategy in the production of vaccines that prevent infections in cattle.

  5. Distribution of Insertion- and Deletion-Associated Genetic Polymorphisms among Four Mycobacterium tuberculosis Phospholipase C Genes and Associations with Extrathoracic Tuberculosis: a Population-Based Study

    OpenAIRE

    Kong, Y.; Cave, M. D.; Yang, D.; Zhang, L.; Marrs, C. F.; Foxman, B.; Bates, J. H.; Wilson, F.; Mukasa, L. N.; Yang, Z. H.

    2005-01-01

    The Mycobacterium tuberculosis genome contains four phospholipase C (PLC)-encoding genes, designated plcA, plcB, plcC, and plcD, respectively. Each of the four genes contributes to the overall PLC activity of M. tuberculosis. PLC is hypothesized to contribute to M. tuberculosis virulence. Infection of M. tuberculosis strains carrying a truncated plcD gene is associated with the occurrence of extrathoracic tuberculosis. However, whether the other three plc genes are also associated with extrat...

  6. Truncated conformal space approach to scaling Lee-Yang model

    International Nuclear Information System (INIS)

    Yurov, V.P.; Zamolodchikov, Al.B.

    1989-01-01

    A numerical approach to 2D relativstic field theories is suggested. Considering a field theory model as an ultraviolet conformal field theory perturbed by suitable relevant scalar operator one studies it in finite volume (on a circle). The perturbed Hamiltonian acts in the conformal field theory space of states and its matrix elements can be extracted from the conformal field theory. Truncation of the space at reasonable level results in a finite dimensional problem for numerical analyses. The nonunitary field theory with the ultraviolet region controlled by the minimal conformal theory μ(2/5) is studied in detail. 9 refs.; 17 figs

  7. Phospholipid lateral diffusion in phosphatidylcholine-sphingomyelin-cholesterol monolayers; Effects of oxidatively truncated phosphatidylcholines

    Czech Academy of Sciences Publication Activity Database

    Parkkila, P.; Štefl, Martin; Olžyńska, Agnieszka; Hof, Martin; Kinnunen, P. K. J.

    2015-01-01

    Roč. 1848, č. 1 (2015), s. 167-173 ISSN 0005-2736 R&D Projects: GA ČR GBP208/12/G016 Institutional support: RVO:61388955 Keywords : Oxidatively truncated phosphatidylcholines * Lateral diffusion * Fluorescence correlation spectroscopy Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.687, year: 2015

  8. Expression of a truncated receptor protein tyrosine phosphatase kappa in the brain of an adult transgenic mouse

    DEFF Research Database (Denmark)

    Shen, P; Canoll, P D; Sap, J

    1999-01-01

    that goal, we have used this mouse model to map the distribution of the truncated RPTP-kappa/beta-geo fusion protein in the adult mouse brain using beta-galactosidase as a marker enzyme. Visualization of the beta-galactosidase activity revealed a non-random pattern of expression, and identified cells......-6596]. Nevertheless, since the transgene's expression is driven by the endogenous RPTP-kappa promoter, distribution of the truncated RPTP-kappa/beta-geo fusion protein should reflect the regional and cellular expression of wild-type RPTP-kappa, and thus may identify sites where RPTP-kappa is important. Towards...

  9. Entanglement entropy from the truncated conformal space

    Directory of Open Access Journals (Sweden)

    T. Palmai

    2016-08-01

    Full Text Available A new numerical approach to entanglement entropies of the Rényi type is proposed for one-dimensional quantum field theories. The method extends the truncated conformal spectrum approach and we will demonstrate that it is especially suited to study the crossover from massless to massive behavior when the subsystem size is comparable to the correlation length. We apply it to different deformations of massless free fermions, corresponding to the scaling limit of the Ising model in transverse and longitudinal fields. For massive free fermions the exactly known crossover function is reproduced already in very small system sizes. The new method treats ground states and excited states on the same footing, and the applicability for excited states is illustrated by reproducing Rényi entropies of low-lying states in the transverse field Ising model.

  10. Quasi-SU(3) truncation scheme for even-even sd-shell nuclei

    International Nuclear Information System (INIS)

    Vargas, C.E.; Hirsch, J.G.; Draayer, J.P.

    2001-01-01

    The quasi-SU(3) symmetry was uncovered in full pf and sdg shell-model calculations for both even-even and odd-even nuclei. It manifests itself through a dominance of single-particle and quadrupole-quadrupole terms in a Hamiltonian used to describe well-deformed nuclei. A practical consequence of the quasi-SU(3) symmetry is an efficient basis truncation scheme. In [C.E. Vargas et al., Phys. Rev. C 58 (1998) 1488] it is shown that when this type of Hamiltonian is diagonalized in an SU(3) basis, only a few irreducible representations (irreps) of SU(3) are needed to describe the yrast band, the leading S=0 irrep augmented with the leading S=1 irreps in the proton and neutron subspaces. In the present article the quasi-SU(3) truncation scheme is used, in conjunction with a 'realistic but schematic' Hamiltonian that includes the most important multipole terms, to describe the energy spectra and B(E2) transition strengths of 20,22 Ne, 24 Mg and 28 Si. The effect of the size of the Hilbert space on both sets of observables is discussed, as well as the structure of the yrast band and the importance of the various terms in the Hamiltonian. The limitations of the model are explicitly discussed

  11. On the propagation of truncated localized waves in dispersive silica

    KAUST Repository

    Salem, Mohamed

    2010-01-01

    Propagation characteristics of truncated Localized Waves propagating in dispersive silica and free space are numerically analyzed. It is shown that those characteristics are affected by the changes in the relation between the transverse spatial spectral components and the wave vector. Numerical experiments demonstrate that as the non-linearity of this relation gets stronger, the pulses propagating in silica become more immune to decay and distortion whereas the pulses propagating in free-space suffer from early decay and distortion. © 2010 Optical Society of America.

  12. Expression of Mesenchymal Stem Cells-Related Genes and Plasticity of Aspirated Follicular Cells Obtained from Infertile Women

    Directory of Open Access Journals (Sweden)

    Edo Dzafic

    2014-01-01

    Full Text Available After removal of oocytes for in vitro fertilization, follicular aspirates which are rich in somatic follicular cells are discarded in daily medical practice. However, there is some evidence that less differentiated cells with stem cell characteristics are present among aspirated follicular cells (AFCs. The aim of this study was to culture AFCs in vitro and to analyze their gene expression profile. Using the RT2 Profiler PCR array, we investigated the expression profile of 84 genes related to stemness, mesenchymal stem cells (MCSs, and cell differentiation in AFCs enriched by hypoosmotic protocol from follicular aspirates of infertile women involved in assisted reproduction programme in comparison with bone marrow-derived mesenchymal stem cells (BM-MSCs and fibroblasts. Altogether the expression of 57 genes was detected in AFCs: 16 genes (OCT4, CD49f, CD106, CD146, CD45, CD54, IL10, IL1B, TNF, VEGF, VWF, HDAC1, MITF, RUNX2, PPARG, and PCAF were upregulated and 20 genes (FGF2, CASP3, CD105, CD13, CD340, CD73, CD90, KDR, PDGFRB, BDNF, COL1A1, IL6, MMP2, NES, NUDT6, BMP6, SMURF2, BMP4, GDF5, and JAG1 were downregulated in AFCs when compared with BM-MSCs. The genes which were upregulated in AFCs were mostly related to MSCs and connected with ovarian function, and differed from those in fibroblasts. The cultured AFCs with predominating granulosa cells were successfully in vitro differentiated into adipogenic-, osteogenic-, and pancreatic-like cells. The upregulation of some MSC-specific genes and in vitro differentiation into other types of cells indicated a subpopulation of AFCs with specific stemness, which was not similar to those of BM-MSCs or fibroblasts.

  13. Mutations in the Gene PRRT2 Cause Paroxysmal Kinesigenic Dyskinesia with Infantile Convulsions

    Directory of Open Access Journals (Sweden)

    Hsien-Yang Lee

    2012-01-01

    Full Text Available Paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC is an episodic movement disorder with autosomal-dominant inheritance and high penetrance, but the causative genetic mutation is unknown. We have now identified four truncating mutations involving the gene PRRT2 in the vast majority (24/25 of well-characterized families with PKD/IC. PRRT2 truncating mutations were also detected in 28 of 78 additional families. PRRT2 encodes a proline-rich transmembrane protein of unknown function that has been reported to interact with the t-SNARE, SNAP25. PRRT2 localizes to axons but not to dendritic processes in primary neuronal culture, and mutants associated with PKD/IC lead to dramatically reduced PRRT2 levels, leading ultimately to neuronal hyperexcitability that manifests in vivo as PKD/IC.

  14. Follow-up study of abnormal biological indicators and gene expression in the peripheral blood of three accidentally exposed persons

    International Nuclear Information System (INIS)

    Chi Cuiping; Wang Haiyan; Wei Jinping; Guo Jianping; Li Shufang; Tian Rong; Guo Fengling; Liu Huifang

    2013-01-01

    In order to identify biomarkers for early diagnosis and/or for therapeutic targets in the delayed health effects of ionizing radiation, we analyzed the subgroups of lymphocytes, serum protein levels and gene expression profiles in the peripheral blood of three 60 Co γ-ray accidentally exposed persons during the three years after irradiation. Flow cytometry analyses and agarose gel electrophoresis were applied to investigate the subgroups of lymphocytes and the composition of serum proteins, respectively. Gene expression profiling was obtained using a whole genome gene expression chip assay. Both the percentage of CD4+ T lymphocytes and the ratio of Th to Ts were reduced compared with the normal control values. The percentage of albumin decreased whereas beta globulin increased. There were 285 up-regulated and 446 down-regulated genes in irradiated samples relative to the control samples. The expression of KDR, CEACAM8 and OSM was validated by RT-PCR. The majority of the differentially expressed genes encode proteins associated with the immune response, inflammation, oncogenesis, cell structure, oxidative stress, neuro-hormone regulation, reproduction, susceptibility to psychiatric disorders, or transcriptional regulation. We have identified a number of promising novel candidates that have potential for serving as biomarkers for delayed damage. Furthermore, the changes in the immunological indicator CD4+ T cells, and the ratio of CD4+ T to CD8+ T cells may be biomarkers for the prediction of delayed damage by ionizing radiation. The findings of our study are useful for forming a comprehensive understanding of the mechanisms underlying the delayed effects of ionizing radiation. (author)

  15. Ab Initio Study of 40Ca with an Importance Truncated No-Core Shell Model

    Energy Technology Data Exchange (ETDEWEB)

    Roth, R; Navratil, P

    2007-05-22

    We propose an importance truncation scheme for the no-core shell model, which enables converged calculations for nuclei well beyond the p-shell. It is based on an a priori measure for the importance of individual basis states constructed by means of many-body perturbation theory. Only the physically relevant states of the no-core model space are considered, which leads to a dramatic reduction of the basis dimension. We analyze the validity and efficiency of this truncation scheme using different realistic nucleon-nucleon interactions and compare to conventional no-core shell model calculations for {sup 4}He and {sup 16}O. Then, we present the first converged calculations for the ground state of {sup 40}Ca within no-core model spaces including up to 16{h_bar}{Omega}-excitations using realistic low-momentum interactions. The scheme is universal and can be easily applied to other quantum many-body problems.

  16. Solution of the Stieltjes truncated matrix moment problem

    Directory of Open Access Journals (Sweden)

    Vadim M. Adamyan

    2005-01-01

    Full Text Available The truncated Stieltjes matrix moment problem consisting in the description of all matrix distributions \\(\\boldsymbol{\\sigma}(t\\ on \\([0,\\infty\\ with given first \\(2n+1\\ power moments \\((\\mathbf{C}_j_{n=0}^j\\ is solved using known results on the corresponding Hamburger problem for which \\(\\boldsymbol{\\sigma}(t\\ are defined on \\((-\\infty,\\infty\\. The criterion of solvability of the Stieltjes problem is given and all its solutions in the non-degenerate case are described by selection of the appropriate solutions among those of the Hamburger problem for the same set of moments. The results on extensions of non-negative operators are used and a purely algebraic algorithm for the solution of both Hamburger and Stieltjes problems is proposed.

  17. Developmental regulation of human truncated nerve growth factor receptor

    Energy Technology Data Exchange (ETDEWEB)

    DiStefano, P.S.; Clagett-Dame, M.; Chelsea, D.M.; Loy, R. (Abbott Laboratories, Abbott Park, IL (USA))

    1991-01-01

    Monoclonal antibodies (designated XIF1 and IIIG5) recognizing distinct epitopes of the human truncated nerve growth factor receptor (NGF-Rt) were used in a two-site radiometric immunosorbent assay to monitor levels of NGF-Rt in human urine as a function of age. Urine samples were collected from 70 neurologically normal subjects ranging in age from 1 month to 68 years. By using this sensitive two-site radiometric immunosorbent assay, NGF-Rt levels were found to be highest in urine from 1-month old subjects. By 2.5 months, NGF-Rt values were half of those seen at 1 month and decreased more gradually between 0.5 and 15 years. Between 15 and 68 years, urine NGF-Rt levels were relatively constant at 5% of 1-month values. No evidence for diurnal variation of adult NGF-Rt was apparent. Pregnant women in their third trimester showed significantly elevated urine NGF-Rt values compared with age-matched normals. Affinity labeling of NGF-Rt with 125I-NGF followed by immunoprecipitation with ME20.4-IgG and gel autoradiography indicated that neonatal urine contained high amounts of truncated receptor (Mr = 50 kd); decreasingly lower amounts of NGF-Rt were observed on gel autoradiograms with development, indicating that the two-site radiometric immunosorbent assay correlated well with the affinity labeling technique for measuring NGF-Rt. NGF-Rt in urines from 1-month-old and 36-year-old subjects showed no differences in affinities for NGF or for the monoclonal antibody IIIG5. These data show that NGF-Rt is developmentally regulated in human urine, and are discussed in relation to the development and maturation of the peripheral nervous system.

  18. Developmental regulation of human truncated nerve growth factor receptor

    International Nuclear Information System (INIS)

    DiStefano, P.S.; Clagett-Dame, M.; Chelsea, D.M.; Loy, R.

    1991-01-01

    Monoclonal antibodies (designated XIF1 and IIIG5) recognizing distinct epitopes of the human truncated nerve growth factor receptor (NGF-Rt) were used in a two-site radiometric immunosorbent assay to monitor levels of NGF-Rt in human urine as a function of age. Urine samples were collected from 70 neurologically normal subjects ranging in age from 1 month to 68 years. By using this sensitive two-site radiometric immunosorbent assay, NGF-Rt levels were found to be highest in urine from 1-month old subjects. By 2.5 months, NGF-Rt values were half of those seen at 1 month and decreased more gradually between 0.5 and 15 years. Between 15 and 68 years, urine NGF-Rt levels were relatively constant at 5% of 1-month values. No evidence for diurnal variation of adult NGF-Rt was apparent. Pregnant women in their third trimester showed significantly elevated urine NGF-Rt values compared with age-matched normals. Affinity labeling of NGF-Rt with 125I-NGF followed by immunoprecipitation with ME20.4-IgG and gel autoradiography indicated that neonatal urine contained high amounts of truncated receptor (Mr = 50 kd); decreasingly lower amounts of NGF-Rt were observed on gel autoradiograms with development, indicating that the two-site radiometric immunosorbent assay correlated well with the affinity labeling technique for measuring NGF-Rt. NGF-Rt in urines from 1-month-old and 36-year-old subjects showed no differences in affinities for NGF or for the monoclonal antibody IIIG5. These data show that NGF-Rt is developmentally regulated in human urine, and are discussed in relation to the development and maturation of the peripheral nervous system

  19. Effect of Truncating AUC at 12, 24 and 48 hr When Evaluating the Bioequivalence of Drugs with a Long Half-Life.

    Science.gov (United States)

    Moreno, Isabel; Ochoa, Dolores; Román, Manuel; Cabaleiro, Teresa; Abad-Santos, Francisco

    2016-01-01

    Bioequivalence studies of drugs with a long half-life require long periods of time for pharmacokinetic sampling. The latest update of the European guideline allows the area under the curve (AUC) truncated at 72 hr to be used as an alternative to AUC0-t as the primary parameter. The objective of this study was to evaluate the effect of truncating the AUC at 48, 24 and 12 hr on the acceptance of the bioequivalence criterion as compared with truncation at 72 hr in bioequivalence trials. The effect of truncated AUC on the within-individual coefficient of variation (CVw) and on the ratio of the formulations was also analysed. Twenty-eight drugs were selected from bioequivalence trials. Pharmacokinetic data were analysed using WinNonLin 2.0 based on the trapezoidal method. Analysis of variance (ANOVA) was performed to obtain the ratios and 90% confidence intervals for AUC at different time-points. The degree of agreement of AUC0-72 in relation to AUC0-48 and AUC0-24, according to the Landis and Koch classification, was 'almost perfect'. Statistically significant differences were observed when the CVw of AUC truncated at 72, 48 and 24 hr was compared with the CVw of AUC0-12. There were no statistically significant differences in the AUC ratio at any time-point. Compared to AUC0-72, Pearson's correlation coefficient for mean AUC, AUC ratio and AUC CVw was worse for AUC0-12 than AUC0-24 or AUC0-48. These preliminary results could suggest that AUC truncation at 24 or 48 hr is adequate to determine whether two formulations are bioequivalent. © 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  20. Truncation effects in connected arrays: Analytical models to describe the edge-induced wave phenomena

    NARCIS (Netherlands)

    Neto, A.; Cavallo, D.; Gerini, G.

    2011-01-01

    This paper presents a Green's function based procedure to assess edge effects in finite wideband connected arrays. Truncation effects are more severe in broadband arrays, since the inter-element mutual coupling facilitates the propagation of edge-born waves that can become dominant over large

  1. Electron transfer reactions, cyanide and O2 binding of truncated hemoglobin from Bacillus subtilis

    DEFF Research Database (Denmark)

    Fernandez, Esther; Larsson, Jonas T.; McLean, Kirsty J.

    2013-01-01

    The truncated hemoglobin from Bacillus subtilis (trHb-Bs) possesses a surprisingly high affinity for oxygen and resistance to (auto)oxidation; its physiological role in the bacterium is not understood and may be connected with its very special redox and ligand binding reactions. Electron transfer...

  2. One-step green synthesis of cuprous oxide crystals with truncated octahedra shapes via a high pressure flux approach

    International Nuclear Information System (INIS)

    Li Benxian; Wang Xiaofeng; Xia Dandan; Chu Qingxin; Liu Xiaoyang; Lu Fengguo; Zhao Xudong

    2011-01-01

    Cuprous oxide (Cu 2 O) was synthesized via reactions between cupric oxide (CuO) and copper metal (Cu) at a low temperature of 300 deg. C. This progress is green, environmentally friendly and energy efficient. Cu 2 O crystals with truncated octahedra morphology were grown under high pressure using sodium hydroxide (NaOH) and potassium hydroxide (KOH) with a molar ratio of 1:1 as a flux. The growth mechanism of Cu 2 O polyhedral microcrystals are proposed and discussed. - Graphical Abstract: The Cu 2 O crystals with truncated octahedral shape were one-step synthesized in high yield via high pressure flux method for the first time, which is green and environmentally friendly. The mechanisms of synthesis and crystal growth were discussed in this paper. Highlights: → Cuprous oxide was one-step green synthesized by high pressure flux method. → The approach was based on the reverse dismutation reactions between cupric oxide and copper metal. → This progress is green, environmentally friendly and energy efficient. → The synthesized Cu2O crystals were of truncated octahedra morphology.

  3. Shell model truncation schemes for rotational nuclei

    International Nuclear Information System (INIS)

    Halse, P.; Jaqua, L.; Barrett, B.R.

    1990-01-01

    The suitability of the pair condensate approach for rotational states is studied in a single j = 17/2 shell of identical nucleons interacting through a quadrupole-quadrupole hamiltonian. The ground band and a K = 2 excited band are both studied in detail. A direct comparison of the exact states with those constituting the SD and SDG subspaces is used to identify the important degrees of freedom for these levels. The range of pairs necessary for a good description is found to be highly state dependent; S and D pairs are the major constituents of the low-spin ground band levels, while G pairs are needed for those in the γ-band. Energy spectra are obtained for each truncated subspace. SDG pairs allow accurate reproduction of the binding energy and K = 2 excitation energy, but still give a moment of inertia which is about 30% too small even for the lowest levels

  4. Joint survival probability via truncated invariant copula

    International Nuclear Information System (INIS)

    Kim, Jeong-Hoon; Ma, Yong-Ki; Park, Chan Yeol

    2016-01-01

    Highlights: • We have studied an issue of dependence structure between default intensities. • We use a multivariate shot noise intensity process, where jumps occur simultaneously and their sizes are correlated. • We obtain the joint survival probability of the integrated intensities by using a copula. • We apply our theoretical result to pricing basket default swap spread. - Abstract: Given an intensity-based credit risk model, this paper studies dependence structure between default intensities. To model this structure, we use a multivariate shot noise intensity process, where jumps occur simultaneously and their sizes are correlated. Through very lengthy algebra, we obtain explicitly the joint survival probability of the integrated intensities by using the truncated invariant Farlie–Gumbel–Morgenstern copula with exponential marginal distributions. We also apply our theoretical result to pricing basket default swap spreads. This result can provide a useful guide for credit risk management.

  5. N-terminally truncated forms of human cathepsin F accumulate in aggresome-like inclusions.

    Science.gov (United States)

    Jerič, Barbara; Dolenc, Iztok; Mihelič, Marko; Klarić, Martina; Zavašnik-Bergant, Tina; Gunčar, Gregor; Turk, Boris; Turk, Vito; Stoka, Veronika

    2013-10-01

    The contribution of individual cysteine cathepsins as positive mediators of programmed cell death is dependent on several factors, such as the type of stimuli, intensity and duration of the stimulus, and cell type involved. Of the eleven human cysteine cathepsins, cathepsin F is the only cathepsin that exhibits an extended N-terminal proregion, which contains a cystatin-like domain. We predicted that the wild-type human cathepsin F contains three natively disordered regions within the enzyme's propeptide and various amino acid stretches with high fibrillation propensity. Wild-type human cathepsin F and its N-terminally truncated forms, Ala(20)-Asp(484) (Δ(19)CatF), Pro(126)-Asp(484) (Δ(125)CatF), and Met(147)-Asp(484) (Δ(146)CatF) were cloned into the pcDNA3 vector and overexpressed in HEK 293T cells. Wild-type human cathepsin F displayed a clear vesicular labeling and colocalized with the LAMP2 protein, a lysosomal marker. However, all three N-terminally truncated forms of human cathepsin F were recovered as insoluble proteins, suggesting that the deletion of at least the signal peptides (Δ(19)CatF), results in protein aggregation. Noteworthy, they concentrated large perinuclear-juxtanuclear aggregates that accumulated within aggresome-like inclusions. These inclusions showed p62-positive immunoreactivity and were colocalized with the autophagy marker LC3B, but not with the LAMP2 protein. In addition, an approximately 2-3 fold increase in DEVDase activity was not sufficient to induce apoptotic cell death. These results suggested the clearance of the N-terminally truncated forms of human cathepsin F via the autophagy pathway, underlying its protective and prosurvival mechanisms. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

  6. Hardware Design and Implementation of Fixed-Width Standard and Truncated 4×4, 6×6, 8×8 and 12×12-BIT Multipliers Using Fpga

    Science.gov (United States)

    Rais, Muhammad H.

    2010-06-01

    This paper presents Field Programmable Gate Array (FPGA) implementation of standard and truncated multipliers using Very High Speed Integrated Circuit Hardware Description Language (VHDL). Truncated multiplier is a good candidate for digital signal processing (DSP) applications such as finite impulse response (FIR) and discrete cosine transform (DCT). Remarkable reduction in FPGA resources, delay, and power can be achieved using truncated multipliers instead of standard parallel multipliers when the full precision of the standard multiplier is not required. The truncated multipliers show significant improvement as compared to standard multipliers. Results show that the anomaly in Spartan-3 AN average connection and maximum pin delay have been efficiently reduced in Virtex-4 device.

  7. On the Minimax Value in the Scale Model with Truncated Data

    OpenAIRE

    Gajek, Leslaw

    1988-01-01

    Let $X$ be a positive random variable with Lebesgue density $f_\\theta(x)$, where $\\theta$ is the scale parameter, and let $Y$ be a positive random variable independent of $X$. We consider two models of truncation: the LHS model, where the data consist only of those observations of $X$ for which $X > Y$; and the RHS model, where the data consist of those observations of $X$ for which $X \\leq Y$. Consider the problem of estimating $\\theta^s, s \

  8. Bioinformatics Analyses of the Role of Vascular Endothelial Growth Factor in Patients with Non-Small Cell Lung Cancer.

    Directory of Open Access Journals (Sweden)

    Ying Wang

    Full Text Available This study was aimed to identify the expression pattern of vascular endothelial growth factor (VEGF in non-small cell lung cancer (NSCLC and to explore its potential correlation with the progression of NSCLC.Gene expression profile GSE39345 was downloaded from the Gene Expression Omnibus database. Twenty healthy controls and 32 NSCLC samples before chemotherapy were analyzed to identify the differentially expressed genes (DEGs. Then pathway enrichment analysis of the DEGs was performed and protein-protein interaction networks were constructed. Particularly, VEGF genes and the VEGF signaling pathway were analyzed. The sub-network was constructed followed by functional enrichment analysis.Total 1666 up-regulated and 1542 down-regulated DEGs were identified. The down-regulated DEGs were mainly enriched in the pathways associated with cancer. VEGFA and VEGFB were found to be the initiating factor of VEGF signaling pathway. In addition, in the epidermal growth factor receptor (EGFR, VEGFA and VEGFB associated sub-network, kinase insert domain receptor (KDR, fibronectin 1 (FN1, transforming growth factor beta induced (TGFBI and proliferating cell nuclear antigen (PCNA were found to interact with at least two of the three hub genes. The DEGs in this sub-network were mainly enriched in Gene Ontology terms related to cell proliferation.EGFR, KDR, FN1, TGFBI and PCNA may interact with VEGFA to play important roles in NSCLC tumorigenesis. These genes and corresponding proteins may have the potential to be used as the targets for either diagnosis or treatment of patients with NSCLC.

  9. Algorithmic impediments filtration using the α-truncated mean method in resolver-to-digital converter

    Directory of Open Access Journals (Sweden)

    Gordiyenko V. I.

    2009-02-01

    Full Text Available A test diagram of the microcontroller-type resolver-to-digital converter and algorithms for impediments filtration therein are developed. Experimental verification of the α-truncated mean algorithm intended for the suppression of impulse and noise interference is conducted. The test results are given.

  10. An analysis of longitudinal data with nonignorable dropout using the truncated multivariate normal distribution

    NARCIS (Netherlands)

    Jolani, Shahab

    2014-01-01

    For a vector of multivariate normal when some elements, but not necessarily all, are truncated, we derive the moment generating function and obtain expressions for the first two moments involving the multivariate hazard gradient. To show one of many applications of these moments, we then extend the

  11. A truncated accretion disk in the galactic black hole candidate source H1743-322

    International Nuclear Information System (INIS)

    Sriram, Kandulapati; Agrawal, Vivek Kumar; Rao, Arikkala Raghurama

    2009-01-01

    To investigate the geometry of the accretion disk in the source H1743-322, we have carried out a detailed X-ray temporal and spectral study using RXTE pointed observations. We have selected all data pertaining to the Steep Power Law (SPL) state during the 2003 outburst of this source. We find anti-correlated hard X-ray lags in three of the observations and the changes in the spectral and timing parameters (like the QPO frequency) confirm the idea of a truncated accretion disk in this source. Compiling data from similar observations of other sources, we find a correlation between the fractional change in the QPO frequency and the observed delay. We suggest that these observations indicate a definite size scale in the inner accretion disk (the radius of the truncated disk) and we explain the observed correlation using various disk parameters like Compton cooling time scale, viscous time scale etc. (research papers)

  12. The remnant of the European rabbit (Oryctolagus cuniculus IgD gene.

    Directory of Open Access Journals (Sweden)

    Dennis K Lanning

    Full Text Available Although IgD first appeared, along with IgM, in the cartilaginous fishes and has been retained throughout subsequent vertebrate evolution, it has been lost in a diverse group of vertebrate species. We previously showed that, unlike vertebrates that express IgD, the rabbit lacks an IgD (Cδ gene within 13.5 kb downstream of the IgM gene. We report here that, by conducting BLAST searches of rabbit Ig heavy chain genomic DNA with known mammalian IgD exons, we identified the remnant of the rabbit Cδ gene approximately 21 kb downstream of the IgM gene. The remnant Cδ locus lacks the δCH1 and hinge exons, but contains truncated δCH2 and δCH3 exons, as well as largely intact, but non-functional, secretory and transmembrane exons. In addition, we report that the Cδ gene probably became non-functional in leporids at least prior to the divergence of rabbits and hares ~12 million years ago.

  13. On the Computation of Optimal Monotone Mean-Variance Portfolios via Truncated Quadratic Utility

    OpenAIRE

    Ales Cerný; Fabio Maccheroni; Massimo Marinacci; Aldo Rustichini

    2008-01-01

    We report a surprising link between optimal portfolios generated by a special type of variational preferences called divergence preferences (cf. [8]) and optimal portfolios generated by classical expected utility. As a special case we connect optimization of truncated quadratic utility (cf. [2]) to the optimal monotone mean-variance portfolios (cf. [9]), thus simplifying the computation of the latter.

  14. Quasi-SU(3) truncation scheme for even-even sd-shell nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Vargas, C.E. E-mail: cvargas@fis.cinvestav.mx; Hirsch, J.G. E-mail: hirsch@nuclecu.unam.mx; Draayer, J.P. E-mail: draayer@lsu.edu

    2001-07-30

    The quasi-SU(3) symmetry was uncovered in full pf and sdg shell-model calculations for both even-even and odd-even nuclei. It manifests itself through a dominance of single-particle and quadrupole-quadrupole terms in a Hamiltonian used to describe well-deformed nuclei. A practical consequence of the quasi-SU(3) symmetry is an efficient basis truncation scheme. In [C.E. Vargas et al., Phys. Rev. C 58 (1998) 1488] it is shown that when this type of Hamiltonian is diagonalized in an SU(3) basis, only a few irreducible representations (irreps) of SU(3) are needed to describe the yrast band, the leading S=0 irrep augmented with the leading S=1 irreps in the proton and neutron subspaces. In the present article the quasi-SU(3) truncation scheme is used, in conjunction with a 'realistic but schematic' Hamiltonian that includes the most important multipole terms, to describe the energy spectra and B(E2) transition strengths of {sup 20,22}Ne, {sup 24}Mg and {sup 28}Si. The effect of the size of the Hilbert space on both sets of observables is discussed, as well as the structure of the yrast band and the importance of the various terms in the Hamiltonian. The limitations of the model are explicitly discussed.

  15. Expression of a truncated ATHB17 protein in maize increases ear weight at silking.

    Directory of Open Access Journals (Sweden)

    Elena A Rice

    Full Text Available ATHB17 (AT2G01430 is an Arabidopsis gene encoding a member of the α-subclass of the homeodomain leucine zipper class II (HD-Zip II family of transcription factors. The ATHB17 monomer contains four domains common to all class II HD-Zip proteins: a putative repression domain adjacent to a homeodomain, leucine zipper, and carboxy terminal domain. However, it also possesses a unique N-terminus not present in other members of the family. In this study we demonstrate that the unique 73 amino acid N-terminus is involved in regulation of cellular localization of ATHB17. The ATHB17 protein is shown to function as a transcriptional repressor and an EAR-like motif is identified within the putative repression domain of ATHB17. Transformation of maize with an ATHB17 expression construct leads to the expression of ATHB17Δ113, a truncated protein lacking the first 113 amino acids which encodes a significant portion of the repression domain. Because ATHB17Δ113 lacks the repression domain, the protein cannot directly affect the transcription of its target genes. ATHB17Δ113 can homodimerize, form heterodimers with maize endogenous HD-Zip II proteins, and bind to target DNA sequences; thus, ATHB17Δ113 may interfere with HD-Zip II mediated transcriptional activity via a dominant negative mechanism. We provide evidence that maize HD-Zip II proteins function as transcriptional repressors and that ATHB17Δ113 relieves this HD-Zip II mediated transcriptional repression activity. Expression of ATHB17Δ113 in maize leads to increased ear size at silking and, therefore, may enhance sink potential. We hypothesize that this phenotype could be a result of modulation of endogenous HD-Zip II pathways in maize.

  16. Expression of a truncated ATHB17 protein in maize increases ear weight at silking.

    Science.gov (United States)

    Rice, Elena A; Khandelwal, Abha; Creelman, Robert A; Griffith, Cara; Ahrens, Jeffrey E; Taylor, J Philip; Murphy, Lesley R; Manjunath, Siva; Thompson, Rebecca L; Lingard, Matthew J; Back, Stephanie L; Larue, Huachun; Brayton, Bonnie R; Burek, Amanda J; Tiwari, Shiv; Adam, Luc; Morrell, James A; Caldo, Rico A; Huai, Qing; Kouadio, Jean-Louis K; Kuehn, Rosemarie; Sant, Anagha M; Wingbermuehle, William J; Sala, Rodrigo; Foster, Matt; Kinser, Josh D; Mohanty, Radha; Jiang, Dongming; Ziegler, Todd E; Huang, Mingya G; Kuriakose, Saritha V; Skottke, Kyle; Repetti, Peter P; Reuber, T Lynne; Ruff, Thomas G; Petracek, Marie E; Loida, Paul J

    2014-01-01

    ATHB17 (AT2G01430) is an Arabidopsis gene encoding a member of the α-subclass of the homeodomain leucine zipper class II (HD-Zip II) family of transcription factors. The ATHB17 monomer contains four domains common to all class II HD-Zip proteins: a putative repression domain adjacent to a homeodomain, leucine zipper, and carboxy terminal domain. However, it also possesses a unique N-terminus not present in other members of the family. In this study we demonstrate that the unique 73 amino acid N-terminus is involved in regulation of cellular localization of ATHB17. The ATHB17 protein is shown to function as a transcriptional repressor and an EAR-like motif is identified within the putative repression domain of ATHB17. Transformation of maize with an ATHB17 expression construct leads to the expression of ATHB17Δ113, a truncated protein lacking the first 113 amino acids which encodes a significant portion of the repression domain. Because ATHB17Δ113 lacks the repression domain, the protein cannot directly affect the transcription of its target genes. ATHB17Δ113 can homodimerize, form heterodimers with maize endogenous HD-Zip II proteins, and bind to target DNA sequences; thus, ATHB17Δ113 may interfere with HD-Zip II mediated transcriptional activity via a dominant negative mechanism. We provide evidence that maize HD-Zip II proteins function as transcriptional repressors and that ATHB17Δ113 relieves this HD-Zip II mediated transcriptional repression activity. Expression of ATHB17Δ113 in maize leads to increased ear size at silking and, therefore, may enhance sink potential. We hypothesize that this phenotype could be a result of modulation of endogenous HD-Zip II pathways in maize.

  17. Expression of a Truncated ATHB17 Protein in Maize Increases Ear Weight at Silking

    Science.gov (United States)

    Creelman, Robert A.; Griffith, Cara; Ahrens, Jeffrey E.; Taylor, J. Philip; Murphy, Lesley R.; Manjunath, Siva; Thompson, Rebecca L.; Lingard, Matthew J.; Back, Stephanie L.; Larue, Huachun; Brayton, Bonnie R.; Burek, Amanda J.; Tiwari, Shiv; Adam, Luc; Morrell, James A.; Caldo, Rico A.; Huai, Qing; Kouadio, Jean-Louis K.; Kuehn, Rosemarie; Sant, Anagha M.; Wingbermuehle, William J.; Sala, Rodrigo; Foster, Matt; Kinser, Josh D.; Mohanty, Radha; Jiang, Dongming; Ziegler, Todd E.; Huang, Mingya G.; Kuriakose, Saritha V.; Skottke, Kyle; Repetti, Peter P.; Reuber, T. Lynne; Ruff, Thomas G.; Petracek, Marie E.; Loida, Paul J.

    2014-01-01

    ATHB17 (AT2G01430) is an Arabidopsis gene encoding a member of the α-subclass of the homeodomain leucine zipper class II (HD-Zip II) family of transcription factors. The ATHB17 monomer contains four domains common to all class II HD-Zip proteins: a putative repression domain adjacent to a homeodomain, leucine zipper, and carboxy terminal domain. However, it also possesses a unique N-terminus not present in other members of the family. In this study we demonstrate that the unique 73 amino acid N-terminus is involved in regulation of cellular localization of ATHB17. The ATHB17 protein is shown to function as a transcriptional repressor and an EAR-like motif is identified within the putative repression domain of ATHB17. Transformation of maize with an ATHB17 expression construct leads to the expression of ATHB17Δ113, a truncated protein lacking the first 113 amino acids which encodes a significant portion of the repression domain. Because ATHB17Δ113 lacks the repression domain, the protein cannot directly affect the transcription of its target genes. ATHB17Δ113 can homodimerize, form heterodimers with maize endogenous HD-Zip II proteins, and bind to target DNA sequences; thus, ATHB17Δ113 may interfere with HD-Zip II mediated transcriptional activity via a dominant negative mechanism. We provide evidence that maize HD-Zip II proteins function as transcriptional repressors and that ATHB17Δ113 relieves this HD-Zip II mediated transcriptional repression activity. Expression of ATHB17Δ113 in maize leads to increased ear size at silking and, therefore, may enhance sink potential. We hypothesize that this phenotype could be a result of modulation of endogenous HD-Zip II pathways in maize. PMID:24736658

  18. Ascending-ramp biphasic waveform has a lower defibrillation threshold and releases less troponin I than a truncated exponential biphasic waveform.

    Science.gov (United States)

    Huang, Jian; Walcott, Gregory P; Ruse, Richard B; Bohanan, Scott J; Killingsworth, Cheryl R; Ideker, Raymond E

    2012-09-11

    We tested the hypothesis that the shape of the shock waveform affects not only the defibrillation threshold but also the amount of cardiac damage. Defibrillation thresholds were determined for 11 waveforms-3 ascending-ramp waveforms, 3 descending-ramp waveforms, 3 rectilinear first-phase biphasic waveforms, a Gurvich waveform, and a truncated exponential biphasic waveform-in 6 pigs with electrodes in the right ventricular apex and superior vena cava. The ascending, descending, and rectilinear waveforms had 4-, 8-, and 16-millisecond first phases and a 3.5-millisecond rectilinear second phase that was half the voltage of the first phase. The exponential biphasic waveform had a 60% first-phase and a 50% second-phase tilt. In a second study, we attempted to defibrillate after 10 seconds of ventricular fibrillation with a single ≈30-J shock (6 pigs successfully defibrillated with 8-millisecond ascending, 8-millisecond rectilinear, and truncated exponential biphasic waveforms). Troponin I blood levels were determined before and 2 to 10 hours after the shock. The lowest-energy defibrillation threshold was for the 8-milliseconds ascending ramp (14.6±7.3 J [mean±SD]), which was significantly less than for the truncated exponential (19.6±6.3 J). Six hours after shock, troponin I was significantly less for the ascending-ramp waveform (0.80±0.54 ng/mL) than for the truncated exponential (1.92±0.47 ng/mL) or the rectilinear waveform (1.17±0.45 ng/mL). The ascending ramp has a significantly lower defibrillation threshold and at ≈30 J causes 58% less troponin I release than the truncated exponential biphasic shock. Therefore, the shock waveform affects both the defibrillation threshold and the amount of cardiac damage.

  19. A computational approach for a fluid queue driven by a truncated birth-death process

    NARCIS (Netherlands)

    Lenin, R.B.; Parthasarathy, P.R.

    1999-01-01

    In this paper, we consider a fluid queue driven by a truncated birth-death process with general birth and death rates. We find the equilibrium distribution of the content of the fluid buffer by computing the eigenvalues and eigenvectors of an associated real tridiagonal matrix. We provide efficient

  20. Truncated Levy flights and agenda-based mobility are useful for the assessment of personal human exposure

    International Nuclear Information System (INIS)

    Schlink, Uwe; Ragas, Ad M.J.

    2011-01-01

    Receptor-oriented approaches can assess the individual-specific exposure to air pollution. In such an individual-based model we analyse the impact of human mobility to the personal exposure that is perceived by individuals simulated in an exemplified urban area. The mobility models comprise random walk (reference point mobility, RPM), truncated Levy flights (TLF), and agenda-based walk (RPMA). We describe and review the general concepts and provide an inter-comparison of these concepts. Stationary and ergodic behaviour are explained and applied as well as performance criteria for a comparative evaluation of the investigated algorithms. We find that none of the studied algorithm results in purely random trajectories. TLF and RPMA prove to be suitable for human mobility modelling, because they provide conditions for very individual-specific trajectories and exposure. Suggesting these models we demonstrate the plausibility of their results for exposure to air-borne benzene and the combined exposure to benzene and nonane. - Highlights: → Human exposure to air pollutants is influenced by a person's movement in the urban area. → We provide a simulation study of approaches to modelling personal exposure. → Agenda-based models and truncated Levy flights are recommended for exposure assessment. → The procedure is demonstrated for benzene exposure in an urban region. - Truncated Levy flights and agenda-based mobility are useful for the assessment of personal human exposure.

  1. Neurodegeneration caused by expression of human truncated tau leads to progressive neurobehavioural impairment in transgenic rats.

    Science.gov (United States)

    Hrnkova, Miroslava; Zilka, Norbert; Minichova, Zuzana; Koson, Peter; Novak, Michal

    2007-01-26

    Human truncated tau protein is an active constituent of the neurofibrillary degeneration in sporadic Alzheimer's disease. We have shown that modified tau protein, when expressed as a transgene in rats, induced AD characteristic tau cascade consisting of tau hyperphosphorylation, formation of argyrophilic tangles and sarcosyl-insoluble tau complexes. These pathological changes led to the functional impairment characterized by a variety of neurobehavioural symptoms. In the present study we have focused on the behavioural alterations induced by transgenic expression of human truncated tau. Transgenic rats underwent a battery of behavioural tests involving cognitive- and sensorimotor-dependent tasks accompanied with neurological assessment at the age of 4.5, 6 and 9 months. Behavioural examination of these rats showed altered spatial navigation in Morris water maze resulting in less time spent in target quadrant (popen field was not influenced by transgene expression. However beam walking test revealed that transgenic rats developed progressive sensorimotor disturbances related to the age of tested animals. The disturbances were most pronounced at the age of 9 months (p<0.01). Neurological alterations indicating impaired reflex responses were other added features of behavioural phenotype of this novel transgenic rat. These results allow us to suggest that neurodegeneration, caused by the non-mutated human truncated tau derived from sporadic human AD, result in the neuronal dysfunction consequently leading to the progressive neurobehavioural impairment.

  2. Resolving candidate genes of mouse skeletal muscle QTL via RNA-Seq and expression network analyses

    Directory of Open Access Journals (Sweden)

    Lionikas Arimantas

    2012-11-01

    Full Text Available Abstract Background We have recently identified a number of Quantitative Trait Loci (QTL contributing to the 2-fold muscle weight difference between the LG/J and SM/J mouse strains and refined their confidence intervals. To facilitate nomination of the candidate genes responsible for these differences we examined the transcriptome of the tibialis anterior (TA muscle of each strain by RNA-Seq. Results 13,726 genes were expressed in mouse skeletal muscle. Intersection of a set of 1061 differentially expressed transcripts with a mouse muscle Bayesian Network identified a coherent set of differentially expressed genes that we term the LG/J and SM/J Regulatory Network (LSRN. The integration of the QTL, transcriptome and the network analyses identified eight key drivers of the LSRN (Kdr, Plbd1, Mgp, Fah, Prss23, 2310014F06Rik, Grtp1, Stk10 residing within five QTL regions, which were either polymorphic or differentially expressed between the two strains and are strong candidates for quantitative trait genes (QTGs underlying muscle mass. The insight gained from network analysis including the ability to make testable predictions is illustrated by annotating the LSRN with knowledge-based signatures and showing that the SM/J state of the network corresponds to a more oxidative state. We validated this prediction by NADH tetrazolium reductase staining in the TA muscle revealing higher oxidative potential of the SM/J compared to the LG/J strain (p Conclusion Thus, integration of fine resolution QTL mapping, RNA-Seq transcriptome information and mouse muscle Bayesian Network analysis provides a novel and unbiased strategy for nomination of muscle QTGs.

  3. Seniority truncation in an equations-of-motion approach to the shell model

    International Nuclear Information System (INIS)

    Covello, A.; Andreozzi, F.; Gargano, A.; Porrino, A.

    1989-01-01

    This paper presents an equations-of-motion method for treating shell-model problems within the framework of the seniority scheme. This method can be applied at many levels of approximation and represents therefore a valuable tool to further reduce seniority truncated shell-model spaces. To show its practical value the authors report some results of an extensive study of the N = 82 isotones which is currently under way

  4. Loads experiments study on two-story RC box and truncated conical walls

    International Nuclear Information System (INIS)

    Asega, H.; Iizuka, S.; Kurihara, I.; Kubo, T.

    1987-01-01

    The failure modes of the two specimens were the sliding shear failure. The two specimens showed almost equal deformation at the maximum shear strength. The ratio of the flexural deformation in the deformation of the truncated conical was larger than that of the box wall. The ratio of the shear deformation in the deformation of the two-story RC box wall was larger than that of the flexural deformation. (orig./HP)

  5. An ABCA1 truncation shows no dominant negative effect in a familial hypoalphalipoproteinemia pedigree with three ABCA1 mutations

    Energy Technology Data Exchange (ETDEWEB)

    Sorrenson, Brie; Suetani, Rachel J. [Department of Biochemistry, University of Otago, Dunedin (New Zealand); Bickley, Vivienne M.; George, Peter M. [Clinical Biochemistry, Canterbury Health Laboratories, Christchurch (New Zealand); Williams, Michael J.A. [Department of Medicine, University of Otago, Dunedin (New Zealand); Scott, Russell S. [Lipid and Diabetes Research Group, Christchurch Hospital (New Zealand); McCormick, Sally P.A., E-mail: sally.mccormick@otago.ac.nz [Department of Biochemistry, University of Otago, Dunedin (New Zealand)

    2011-06-10

    Highlights: {yields} Characterisation of an ABCA1 truncation mutant, C978fsX988, in a pedigree with three ABCA1 mutations. {yields} Functional analysis of C978fsX988 in patient fibroblasts and HEK 293 cells shows no cholesterol efflux function. {yields} Allele-specific quantification shows C978fsX988 not expressed at mRNA level in fibroblasts. {yields} Unlike other ABCA1 truncations, C978fsX988 mutant shows no dominant negative effect at mRNA or protein level. -- Abstract: The ATP binding cassette transporter (ABCA1) A1 is a key determinant of circulating high density lipoprotein cholesterol (HDL-C) levels. Mutations in ABCA1 are a major genetic contributor to low HDL-C levels within the general population. Following the finding of three different ABCA1 mutations, p.C978fsX988, p.T1512M and p.N1800H in a subject with hypoalphalipoproteinemia, we aimed to establish whether the p.C978fsX988 truncation exerted a dominant negative effect on the full-length ABCA1 alleles within family members as has been reported for other ABCA1 truncations. Characterisation of the p.C978fsX988 mutant in transfected HEK 293 cells showed it to be expressed as a GFP fusion protein but lacking in cholesterol efflux function. This was in keeping with results from cholesterol efflux assays in the fibroblasts of p.C978fsX988 carriers which also showed impaired efflux. Allele- specific quantification of p.C978fsX988 mRNA and analysis of ABCA1 protein levels in the fibroblasts of p.C978fsX988 heterozygotes showed negligible levels of mRNA and protein expression. There was no evidence of a dominant negative effect on wildtype or p.N1800H protein levels. We conclude that in the case of the p.C978fsX988 truncated mutant a lack of expression precludes it from having a dominant negative effect.

  6. Vortex breakdown in a truncated conical bioreactor

    Energy Technology Data Exchange (ETDEWEB)

    Balci, Adnan; Brøns, Morten [DTU Compute, Technical University of Denmark, DK-2800 Kgs. Lyngby (Denmark); Herrada, Miguel A [E.S.I, Universidad de Sevilla, Camino de los Descubrimientos s/n, E-41092 (Spain); Shtern, Vladimir N, E-mail: mobr@dtu.dk [Shtern Research and Consulting, Houston, TX 77096 (United States)

    2015-12-15

    This numerical study explains the eddy formation and disappearance in a slow steady axisymmetric air–water flow in a vertical truncated conical container, driven by the rotating top disk. Numerous topological metamorphoses occur as the water height, H{sub w}, and the bottom-sidewall angle, α, vary. It is found that the sidewall convergence (divergence) from the top to the bottom stimulates (suppresses) the development of vortex breakdown (VB) in both water and air. At α = 60°, the flow topology changes eighteen times as H{sub w} varies. The changes are due to (a) competing effects of AMF (the air meridional flow) and swirl, which drive meridional motions of opposite directions in water, and (b) feedback of water flow on AMF. For small H{sub w}, the AMF effect dominates. As H{sub w} increases, the swirl effect dominates and causes VB. The water flow feedback produces and modifies air eddies. The results are of fundamental interest and can be relevant for aerial bioreactors. (paper)

  7. Vortex breakdown in a truncated conical bioreactor

    International Nuclear Information System (INIS)

    Balci, Adnan; Brøns, Morten; Herrada, Miguel A; Shtern, Vladimir N

    2015-01-01

    This numerical study explains the eddy formation and disappearance in a slow steady axisymmetric air–water flow in a vertical truncated conical container, driven by the rotating top disk. Numerous topological metamorphoses occur as the water height, H w , and the bottom-sidewall angle, α, vary. It is found that the sidewall convergence (divergence) from the top to the bottom stimulates (suppresses) the development of vortex breakdown (VB) in both water and air. At α = 60°, the flow topology changes eighteen times as H w varies. The changes are due to (a) competing effects of AMF (the air meridional flow) and swirl, which drive meridional motions of opposite directions in water, and (b) feedback of water flow on AMF. For small H w , the AMF effect dominates. As H w increases, the swirl effect dominates and causes VB. The water flow feedback produces and modifies air eddies. The results are of fundamental interest and can be relevant for aerial bioreactors. (paper)

  8. Dehalogenimonas lykanthroporepellens BL-DC-9T simultaneously transcribes many rdhA genes during organohalide respiration with 1,2-DCA, 1,2-DCP, and 1,2,3-TCP as electron acceptors.

    Science.gov (United States)

    Mukherjee, Kalpataru; Bowman, Kimberly S; Rainey, Fred A; Siddaramappa, Shivakumara; Challacombe, Jean F; Moe, William M

    2014-05-01

    The genome sequence of the organohalide-respiring bacterium Dehalogenimonas lykanthroporepellensBL-DC-9(T) contains numerous loci annotated as reductive dehalogenase homologous (rdh) genes based on inferred protein sequence identity with functional dehalogenases of other bacterial species. Many of these genes are truncated, lack adjacent regulatory elements, or lack cognate genes coding for membrane-anchoring proteins typical of the functionally characterized active reductive dehalogenases of organohalide-respiring bacteria. To investigate the expression patterns of the rdh genes in D. lykanthroporepellensBL-DC-9(T), oligonucleotide primers were designed to uniquely target 25 rdh genes present in the genome as well as four putative regulatory genes. RNA extracts from cultures of strain BL-DC-9(T) actively dechlorinating three different electron acceptors, 1,2-dichloroethane, 1,2-dichloropropane, and 1,2,3-trichloropropane were reverse-transcribed and subjected to PCR amplification using rdh-specific primers. Nineteen rdh gene transcripts, including 13 full-length rdhA genes, six truncated rdhA genes, and five rdhA genes having cognate rdhB genes were consistently detected during the dechlorination of all three of the polychlorinated alkanes tested. Transcripts from all four of the putative regulatory genes were also consistently detected. Results reported here expand the diversity of bacteria known to simultaneously transcribe multiple rdh genes and provide insights into the transcription factors associated with rdh gene expression. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  9. Effect of truncated glucagon-like peptide-1 [proglucagon-(78-107) amide] on endocrine secretion from pig pancreas, antrum, and nonantral stomach

    DEFF Research Database (Denmark)

    Orskov, C; Holst, J J; Nielsen, O V

    1988-01-01

    We studied the effect of truncated glucagon-like peptide-1 [naturally occurring GLP-1; proglucagon-(78-107) amide], a potent insulinotropic peptide from the pig ileum, on endocrine and exocrine secretion of potential gastrointestinal target organs using isolated perfused preparations of the porcine...... pancreas, antrum, and nonantral part of the stomach. Truncated GLP-1 significantly increased somatostatin secretion from the pancreas at 10(-10) mol/liter and more than doubled the secretion at 10(-9) mol/liter, but had no effect on either somatostatin or gastrin secretion from the antrum...... or on somatostatin secretion from the nonantral stomach in concentrations up to 10(-8) mol/liter. Insulin secretion from the pancreas (with 7 mmol/liter glucose in the perfusate) increased 2-fold with truncated GLP-1 at 10(-10) mol/liter and almost 5-fold at 10(-9) mol/liter. Pancreatic glucagon secretion...

  10. Identification of the gene for Nance-Horan syndrome (NHS).

    Science.gov (United States)

    Brooks, S P; Ebenezer, N D; Poopalasundaram, S; Lehmann, O J; Moore, A T; Hardcastle, A J

    2004-10-01

    The disease intervals for Nance-Horan syndrome (NHS [MIM 302350]) and X linked congenital cataract (CXN) overlap on Xp22. To identify the gene or genes responsible for these diseases. Families with NHS were ascertained. The refined locus for CXN was used to focus the search for candidate genes, which were screened by polymerase chain reaction and direct sequencing of potential exons and intron-exon splice sites. Genomic structures and homologies were determined using bioinformatics. Expression studies were undertaken using specific exonic primers to amplify human fetal cDNA and mouse RNA. A novel gene NHS, with no known function, was identified as causative for NHS. Protein truncating mutations were detected in all three NHS pedigrees, but no mutation was identified in a CXN family, raising the possibility that NHS and CXN may not be allelic. The NHS gene forms a new gene family with a closely related novel gene NHS-Like1 (NHSL1). NHS and NHSL1 lie in paralogous duplicated chromosomal intervals on Xp22 and 6q24, and NHSL1 is more broadly expressed than NHS in human fetal tissues. This study reports the independent identification of the gene causative for Nance-Horan syndrome and extends the number of mutations identified.

  11. CONVERGENCE OF THE FRACTIONAL PARTS OF THE RANDOM VARIABLES TO THE TRUNCATED EXPONENTIAL DISTRIBUTION

    Directory of Open Access Journals (Sweden)

    Bogdan Gheorghe Munteanu

    2013-01-01

    Full Text Available Using the stochastic approximations, in this paper it was studiedthe convergence in distribution of the fractional parts of the sum of random variables to the truncated exponential distribution with parameter lambda. This fact is feasible by means of the Fourier-Stieltjes sequence (FSS of the random variable.

  12. Computing the Moments of Order Statistics from Truncated Pareto Distributions Based on the Conditional Expectation

    Directory of Open Access Journals (Sweden)

    Gökhan Gökdere

    2014-05-01

    Full Text Available In this paper, closed form expressions for the moments of the truncated Pareto order statistics are obtained by using conditional distribution. We also derive some results for the moments which will be useful for moment computations based on ordered data.

  13. Complete Chloroplast Genome of Pinus massoniana (Pinaceae): Gene Rearrangements, Loss of ndh Genes, and Short Inverted Repeats Contraction, Expansion.

    Science.gov (United States)

    Ni, ZhouXian; Ye, YouJu; Bai, Tiandao; Xu, Meng; Xu, Li-An

    2017-09-11

    The chloroplast genome (CPG) of Pinus massoniana belonging to the genus Pinus (Pinaceae), which is a primary source of turpentine, was sequenced and analyzed in terms of gene rearrangements, ndh genes loss, and the contraction and expansion of short inverted repeats (IRs). P. massoniana CPG has a typical quadripartite structure that includes large single copy (LSC) (65,563 bp), small single copy (SSC) (53,230 bp) and two IRs (IRa and IRb, 485 bp). The 108 unique genes were identified, including 73 protein-coding genes, 31 tRNAs, and 4 rRNAs. Most of the 81 simple sequence repeats (SSRs) identified in CPG were mononucleotides motifs of A/T types and located in non-coding regions. Comparisons with related species revealed an inversion (21,556 bp) in the LSC region; P. massoniana CPG lacks all 11 intact ndh genes (four ndh genes lost completely; the five remained truncated as pseudogenes; and the other two ndh genes remain as pseudogenes because of short insertions or deletions). A pair of short IRs was found instead of large IRs, and size variations among pine species were observed, which resulted from short insertions or deletions and non-synchronized variations between "IRa" and "IRb". The results of phylogenetic analyses based on whole CPG sequences of 16 conifers indicated that the whole CPG sequences could be used as a powerful tool in phylogenetic analyses.

  14. The identification of point mutations in Duchenne muscular dystrophy patients by using reverse-transcription PCR and the protein truncation test

    Energy Technology Data Exchange (ETDEWEB)

    Gardner, R.J.; Bobrow, M.; Roberts, R.G. [St. Thomas`s Hospitals, London (United Kingdom)

    1995-08-01

    The protein truncation test (PTT) is a mutation-detection method that monitors the integrity of the open reading frame (ORF). More than 60% of cases of Duchenne muscular dystrophy (DMD) result from gross frameshifting deletions in the dystrophin gene that are detectable by multiplex PCR system. It has become apparent that virtually all of the remaining DMD mutations also disrupt the translational reading frame, making the PTT a logical next step toward a comprehensive strategy for the identification of all DMD mutations. We report here a pilot study involving 22 patients and describe the mutations characterized. These constitute 12 point mutations or small insertions/deletions and 4 gross rearrangements. We also have a remaining five patients in whom there does not appear to be mutation in the ORF. We believe that reverse-transcription-PCR/PTT is an efficient method by which to screen for small mutations in DMD patients with no deletion. 29 refs., 2 figs., 3 tabs.

  15. A novel germline mutation in the aryl hydrocarbon receptor-interacting protein (AIP) gene in an Italian family with gigantism.

    Science.gov (United States)

    Urbani, C; Russo, D; Raggi, F; Lombardi, M; Sardella, C; Scattina, I; Lupi, I; Manetti, L; Tomisti, L; Marcocci, C; Martino, E; Bogazzi, F

    2014-10-01

    Acromegaly usually occurs as a sporadic disease, but it may be a part of familial pituitary tumor syndromes in rare cases. Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene have been associated with a predisposition to familial isolated pituitary adenoma. The aim of the present study was to evaluate the AIP gene in a patient with gigantism and in her relatives. Direct sequencing of AIP gene was performed in fourteen members of the family, spanning among three generations. The index case was an 18-year-old woman with gigantism due to an invasive GH-secreting pituitary adenoma and a concomitant tall-cell variant of papillary thyroid carcinoma. A novel germline mutation in the AIP gene (c.685C>T, p.Q229X) was identified in the proband and in two members of her family, who did not present clinical features of acromegaly or other pituitary disorders. Eleven subjects had no mutation in the AIP gene. Two members of the family with clinical features of acromegaly refused either the genetic or the biochemical evaluation. The Q229X mutation was predicted to generate a truncated AIP protein, lacking the last two tetratricopeptide repeat domains and the final C-terminal α-7 helix. We identified a new AIP germline mutation predicted to produce a truncated AIP protein, lacking its biological properties due to the disruption of the C-terminus binding sites for both the chaperones and the client proteins of AIP.

  16. Effect of Synthetic Truncated Apolipoprotein C-I Peptide on Plasma Lipoprotein Cholesterol in Nonhuman Primates

    Directory of Open Access Journals (Sweden)

    Rampratap S. Kushwaha

    2004-01-01

    Full Text Available The present studies were conducted to determine whether a synthetic truncated apoC-I peptide that inhibits CETP activity in baboons would raise plasma HDL cholesterol levels in nonhuman primates with low HDL levels. We used 2 cynomolgus monkeys and 3 baboons fed a cholesterol- and fat-enriched diet. In cynomolgus monkeys, we injected synthetic truncated apoC-I inhibitor peptide at a dose of 20 mg/kg and, in baboons, at doses of 10, 15, and 20 mg/kg at weekly intervals. Blood samples were collected 3 times a week and VLDL + LDL and HDL cholesterol concentrations were measured. In cynomolgus monkeys, administration of the inhibitor peptide caused a rapid decrease in VLDL + LDL cholesterol concentrations (30%–60% and an increase in HDL cholesterol concentrations (10%–20%. VLDL + LDL cholesterol concentrations returned to baseline levels in approximately 15 days. In baboons, administration of the synthetic inhibitor peptide caused a decrease in VLDL + LDL cholesterol (20%–60% and an increase in HDL cholesterol (10%–20%. VLDL + LDL cholesterol returned to baseline levels by day 21, whereas HDL cholesterol concentrations remained elevated for up to 26 days. ApoA-I concentrations increased, whereas apoE and triglyceride concentrations decreased. Subcutaneous and intravenous administrations of the inhibitor peptide had similar effects on LDL and HDL cholesterol concentrations. There was no change in body weight, food consumption, or plasma IgG levels of any baboon during the study. These studies suggest that the truncated apoC-I peptide can be used to raise HDL in humans.

  17. New mutations in the NHS gene in Nance-Horan Syndrome families from the Netherlands.

    Science.gov (United States)

    Florijn, Ralph J; Loves, Willem; Maillette de Buy Wenniger-Prick, Liesbeth J J M; Mannens, Marcel M A M; Tijmes, Nel; Brooks, Simon P; Hardcastle, Alison J; Bergen, Arthur A B

    2006-09-01

    Mutations in the NHS gene cause Nance-Horan Syndrome (NHS), a rare X-chromosomal recessive disorder with variable features, including congenital cataract, microphthalmia, a peculiar form of the ear and dental anomalies. We investigated the NHS gene in four additional families with NHS from the Netherlands, by dHPLC and direct sequencing. We identified an unique mutation in each family. Three out of these four mutations were not reported before. We report here the first splice site sequence alteration mutation and three protein truncating mutations. Our results suggest that X-linked cataract and NHS are allelic disorders.

  18. Missense Mutation in the USH2A Gene: Association with Recessive Retinitis Pigmentosa without Hearing Loss

    OpenAIRE

    Rivolta, Carlo; Sweklo, Elizabeth A.; Berson, Eliot L.; Dryja, Thaddeus P.

    2000-01-01

    Microdeletions Glu767(1-bp del), Thr967(1-bp del), and Leu1446(2-bp del) in the human USH2A gene have been reported to cause Usher syndrome type II, a disorder characterized by retinitis pigmentosa (RP) and mild-to-severe hearing loss. Each of these three frameshift mutations is predicted to lead to an unstable mRNA transcript that, if translated, would result in a truncated protein lacking the carboxy terminus. Here, we report Cys759Phe, a novel missense mutation in this gene that changes an...

  19. Hotspots of missense mutation identify novel neurodevelopmental disorder genes and functional domains

    Science.gov (United States)

    Geisheker, Madeleine R.; Heymann, Gabriel; Wang, Tianyun; Coe, Bradley P.; Turner, Tychele N.; Stessman, Holly A.F.; Hoekzema, Kendra; Kvarnung, Malin; Shaw, Marie; Friend, Kathryn; Liebelt, Jan; Barnett, Christopher; Thompson, Elizabeth M.; Haan, Eric; Guo, Hui; Anderlid, Britt-Marie; Nordgren, Ann; Lindstrand, Anna; Vandeweyer, Geert; Alberti, Antonino; Avola, Emanuela; Vinci, Mirella; Giusto, Stefania; Pramparo, Tiziano; Pierce, Karen; Nalabolu, Srinivasa; Michaelson, Jacob J.; Sedlacek, Zdenek; Santen, Gijs W.E.; Peeters, Hilde; Hakonarson, Hakon; Courchesne, Eric; Romano, Corrado; Kooy, R. Frank; Bernier, Raphael A.; Nordenskjöld, Magnus; Gecz, Jozef; Xia, Kun; Zweifel, Larry S.; Eichler, Evan E.

    2017-01-01

    Although de novo missense mutations have been predicted to account for more cases of autism than gene-truncating mutations, most research has focused on the latter. We identified the properties of de novo missense mutations in patients with neurodevelopmental disorders (NDDs) and highlight 35 genes with excess missense mutations. Additionally, 40 amino acid sites were recurrently mutated in 36 genes, and targeted sequencing of 20 sites in 17,689 NDD patients identified 21 new patients with identical missense mutations. One recurrent site (p.Ala636Thr) occurs in a glutamate receptor subunit, GRIA1. This same amino acid substitution in the homologous but distinct mouse glutamate receptor subunit Grid2 is associated with Lurcher ataxia. Phenotypic follow-up in five individuals with GRIA1 mutations shows evidence of specific learning disabilities and autism. Overall, we find significant clustering of de novo mutations in 200 genes, highlighting specific functional domains and synaptic candidate genes important in NDD pathology. PMID:28628100

  20. Assembly of α-synuclein fibrils in nanoscale studied by peptide truncation and AFM

    International Nuclear Information System (INIS)

    Zhang Feng; Lin Xiaojing; Ji Lina; Du Haining; Tang Lin; He Jianhua; Hu Jun; Hu Hongyu

    2008-01-01

    α-Synuclein (α-Syn) fibrils are the major component of Lewy bodies that are closely associated with the pathogenesis of Parkinson's disease, but the mechanism for the fibril assembly remains poorly understood. Here we report using a combination of peptide truncation and atomic force microscopy (AFM) to elucidate the self-assembly and morphology of the α-Syn fibrils. The results show that protease K significantly slims the fibrils from the mean height of ∼6.6 to ∼4.7 nm, whereas chaotropic denaturant urea completely breaks down the fibrils into small particles. The in situ enzymatic digestion also results in thinning of the fibrils, giving rise to some nicks on the fibrils. Moreover, N- or C-terminally truncated α-Syn fragments assemble into thinner filaments with the heights depending on the peptide lengths. A nine-residue peptide corresponding to the homologous GAV-motif sequence can form very thin (∼2.2 nm) but long (>1 μm) filaments. Thus, the central sequence of α-Syn forms a fibrillar core by cross-β-structure that is flanked by two flexible termini, and the orientation of the fibril growth is perpendicular to the β-sheet structures

  1. Quantification of circulating endothelial progenitor cells using the modified ISHAGE protocol.

    Directory of Open Access Journals (Sweden)

    Caroline Schmidt-Lucke

    2010-11-01

    Full Text Available Circulating endothelial progenitor cells (EPC, involved in endothelial regeneration, neovascularisation, and determination of prognosis in cardiovascular disease can be characterised with functional assays or using immunofluorescence and flow cytometry. Combinations of markers, including CD34+KDR+ or CD133+KDR+, are used. This approach, however may not consider all characteristics of EPC. The lack of a standardised protocol with regards to reagents and gating strategies may account for the widespread inter-laboratory variations in quantification of EPC. We, therefore developed a novel protocol adapted from the standardised so-called ISHAGE protocol for enumeration of haematopoietic stem cells to enable comparison of clinical and laboratory data.In 25 control subjects, 65 patients with coronary artery disease (CAD; 40 stable CAD, 25 acute coronary syndrome/acute myocardial infarction (ACS, EPC were quantified using the following approach: Whole blood was incubated with CD45, KDR, and CD34. The ISHAGE sequential strategy was used, and finally, CD45(dimCD34(+ cells were quantified for KDR. A minimum of 100 CD34(+ events were collected. For comparison, CD45(+CD34(+ and CD45(-CD34(+ were analysed simultaneously. The number of CD45(dimCD34(+KDR(+ cells only were significantly higher in healthy controls compared to patients with CAD or ACS (p = 0.005 each, p<0.001 for trend. An inverse correlation of CD45(dimCD34(+KDR(+ with disease activity (r = -0.475, p<0.001 was confirmed. Only CD45(dimCD34(+KDR(+ correlated inversely with the number of diseased coronaries (r = -0.344; p<0.005. In a second study, a 4-week de-novo treatment of atorvastatin in stable CAD evoked an increase only of CD45(dimCD34(+KDR(+ EPC (p<0.05. CD45(+CD34(+KDR(+ and CD45(-CD34(+KDR(+ were indifferent between the three groups.Our newly established protocol adopted from the standardised ISHAGE protocol achieved higher accuracy in EPC enumeration confirming previous

  2. Occurrence in Mexico, 1998-2008, of Vibrio cholerae CTX+ El Tor carrying an additional truncated CTX prophage.

    Science.gov (United States)

    Alam, Munirul; Rashed, Shah Manzur; Mannan, Shahnewaj Bin; Islam, Tarequl; Lizarraga-Partida, Marcial Leonardo; Delgado, Gabriela; Morales-Espinosa, Rosario; Mendez, Jose Luis; Navarro, Armando; Watanabe, Haruo; Ohnishi, Makoto; Hasan, Nur A; Huq, Anwar; Sack, R Bradley; Colwell, Rita R; Cravioto, Alejandro

    2014-07-08

    The seventh cholera pandemic caused by Vibrio cholerae O1 El Tor (ET) has been superseded in Asia and Africa by altered ET possessing the cholera toxin (CTX) gene of classical (CL) biotype. The CL biotype of V. cholerae was isolated, along with prototypic and altered ET, during the 1991 cholera epidemic in Mexico and subsequently remained endemic until 1997. Microbiological, molecular, and phylogenetic analyses of clinical and environmental V. cholerae isolated in Mexico between 1998 and 2008 revealed important genetic events favoring predominance of ET over CL and altered ET. V. cholerae altered ET was predominant after 1991 but not after 2000. V. cholerae strains isolated between 2001 and 2003 and a majority isolated in 2004 lacked CTX prophage (Φ) genes encoding CTX subunits A and B and repeat sequence transcriptional regulators of ET and CL biotypes: i.e., CTXΦ(-). Most CTXΦ(-) V. cholerae isolated in Mexico between 2001 and 2003 also lacked toxin coregulated pili tcpA whereas some carried either tcpA(ET) or a variant tcpA with noticeable sequence dissimilarity from tcpA(CL). The tcpA variants were not detected in 2005 after CTXΦ(+) ET became dominant. All clinical and environmental V. cholerae O1 strains isolated during 2005-2008 in Mexico were CTXΦ(+) ET, carrying an additional truncated CTXΦ instead of RS1 satellite phage. Despite V. cholerae CTXΦ(-) ET exhibiting heterogeneity in pulsed-field gel electrophoresis patterns, CTXΦ(+) ET isolated during 2004-2008 displayed homogeneity and clonal relationship with V. cholerae ET N16961 and V. cholerae ET isolated in Peru.

  3. Electro-optical study of nanoscale Al-Si-truncated conical photodetector with subwavelength aperture

    Science.gov (United States)

    Karelits, Matityahu; Mandelbaum, Yaakov; Chelly, Avraham; Karsenty, Avi

    2017-10-01

    A type of silicon photodiode has been designed and simulated to probe the optical near field and detect evanescent waves. These waves convey subwavelength resolution. This photodiode consists of a truncated conical shaped, silicon Schottky diode having a subwavelength aperture of 150 nm. Electrical and electro-optical simulations have been conducted. These results are promising toward the fabrication of a new generation of photodetector devices.

  4. A novel mutation in the sterol 27-hydroxylase gene of a woman with autosomal recessive cerebrotendinous xanthomatosis

    Directory of Open Access Journals (Sweden)

    Garuti Rita

    2010-10-01

    Full Text Available Article abstract Mutations of the gene encoding the mitochondrial enzyme sterol 27-hydroxylase (CYP27A1 gene cause defects in the cholesterol pathway to bile acids that lead to the storage of cholestanol and cholesterol in tendons, lenses and the central nervous system. This disorder is the cause of a clinical syndrome known as cerebrotendinous xanthomatosis (CTX. Since 1991 several mutations of the CYP27A1 gene have been reported. We diagnosed the clinical features of CTX in a caucasian woman. Serum levels of cholestanol and 7α-hydroxycholesterol were elevated and the concentration of 27-hydroxycholesterol was reduced. Bile alcohols in the urine and faeces were increased. The analysis of the CYP27A1 gene showed that the patient was a compound heterozygote carrying two mutations both located in exon 8. One mutation is a novel four nucleotide deletion (c.1330-1333delTTCC that results in a frameshift and the occurrence of a premature stop codon leading to the formation of a truncated protein of 448 amino acids. The other mutation, previously reported, is a C - > T transition (c. c.1381C > T that converts the glutamine codon at position 461 into a termination codon (p.Q461X. These truncated proteins are expected to have no biological function being devoid of the cysteine residue at position 476 of the normal enzyme that is crucial for heme binding and enzyme activity.

  5. No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk

    DEFF Research Database (Denmark)

    Easton, Douglas F; Lesueur, Fabienne; Decker, Brennan

    2016-01-01

    BACKGROUND: BRCA1 interacting protein C-terminal helicase 1 (BRIP1) is one of the Fanconi Anaemia Complementation (FANC) group family of DNA repair proteins. Biallelic mutations in BRIP1 are responsible for FANC group J, and previous studies have also suggested that rare protein truncating variants...

  6. Acceptance Sampling Plans Based on Truncated Life Tests for Sushila Distribution

    Directory of Open Access Journals (Sweden)

    Amer Ibrahim Al-Omari

    2018-03-01

    Full Text Available An acceptance sampling plan problem based on truncated life tests when the lifetime following a Sushila distribution is considered in this paper. For various acceptance numbers, confidence levels and values of the ratio between fixed experiment time and particular mean lifetime, the minimum sample sizes required to ascertain a specified mean life were found. The operating characteristic function values of the suggested sampling plans and the producer’s risk are presented. Some tables are provided and the results are illustrated by an example of a real data set.

  7. Cross-layer designed adaptive modulation algorithm with packet combining and truncated ARQ over MIMO Nakagami fading channels

    KAUST Repository

    Aniba, Ghassane

    2011-04-01

    This paper presents an optimal adaptive modulation (AM) algorithm designed using a cross-layer approach which combines truncated automatic repeat request (ARQ) protocol and packet combining. Transmissions are performed over multiple-input multiple-output (MIMO) Nakagami fading channels, and retransmitted packets are not necessarily modulated using the same modulation format as in the initial transmission. Compared to traditional approach, cross-layer design based on the coupling across the physical and link layers, has proven to yield better performance in wireless communications. However, there is a lack for the performance analysis and evaluation of such design when the ARQ protocol is used in conjunction with packet combining. Indeed, previous works addressed the link layer performance of AM with truncated ARQ but without packet combining. In addition, previously proposed AM algorithms are not optimal and can provide poor performance when packet combining is implemented. Herein, we first show that the packet loss rate (PLR) resulting from the combining of packets modulated with different constellations can be well approximated by an exponential function. This model is then used in the design of an optimal AM algorithm for systems employing packet combining, truncated ARQ and MIMO antenna configurations, considering transmission over Nakagami fading channels. Numerical results are provided for operation with or without packet combining, and show the enhanced performance and efficiency of the proposed algorithm in comparison with existing ones. © 2011 IEEE.

  8. A new biotype of Fusarium oxysporum f. sp. lycopersici race 2 emerged by a transposon-driven mutation of avirulence gene AVR1.

    Science.gov (United States)

    Kashiwa, Takeshi; Suzuki, Tatsuya; Sato, Akira; Akai, Kotaro; Teraoka, Tohru; Komatsu, Ken; Arie, Tsutomu

    2016-07-01

    Emergence of races in Fusarium oxysporum f. sp. lycopersici (Fol) is caused by loss or mutation of at least one avirulence (AVR) gene. The product of AVR1 is a small protein (Avr1) secreted by Fol in tomato xylem sap during infection. This protein triggers Fol race 1 specific resistance (I) in tomato, indicating that AVR1 is an AVR gene. Deletion of AVR1 in race 1 resulted in the emergence of race 2, and an additional mutation in AVR2 generated race 3. Previously, we reported a new biotype of race 3, KoChi-1, in which AVR1 was truncated by a transposon Hormin, which suggested a new route to evolution of races in Fol However, to date no race 2 isolate carrying Hormin-truncated AVR1 has been reported. In this report, we describe such isolates, represented by Chiba-5, in which Hormin insertion occurred in AVR1 at a position different from that in KoChi-1. AVR1 truncation in both isolates resulted in production of defective Avr1 proteins. Chiba-5 and KoChi-1 belong to different phylogenetic clades, A1 and A2, respectively, suggesting that insertion of Hormin in AVR1 in Chiba-5 and KoChi-1 occurred as independent evolutionary events. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. A novel alpha-thalassemia nonsense mutation in HBA2: C.382 A > T globin gene.

    Science.gov (United States)

    Hamid, Mohammad; Bokharaei Merci, Hanieh; Galehdari, Hamid; Saberi, Ali Hossein; Kaikhaei, Bijan; Mohammadi-Anaei, Marziye; Ahmadzadeh, Ahmad; Shariati, Gholamreza

    2014-07-01

    In this study, a new alpha globin gene mutation on the α2-globin gene is reported. This mutation resulted in a Lys > stop codon substitution at position 127 which was detected in four individuals (three males and one female). DNA sequencing revealed this mutation in unrelated persons in Khuzestan province, Southwestern Iran of Lor ethnicity. This mutation caused no severe hematological abnormalities in the carriers. From the nature of substituted residues in α2-globin, it is widely expected that this mutation leads to unstable and truncated protein and should be detected in couples at risk for α-thalassemia.

  10. Reducing C-terminal-truncated alpha-synuclein by immunotherapy attenuates neurodegeneration and propagation in Parkinson's disease-like models.

    Science.gov (United States)

    Games, Dora; Valera, Elvira; Spencer, Brian; Rockenstein, Edward; Mante, Michael; Adame, Anthony; Patrick, Christina; Ubhi, Kiren; Nuber, Silke; Sacayon, Patricia; Zago, Wagner; Seubert, Peter; Barbour, Robin; Schenk, Dale; Masliah, Eliezer

    2014-07-09

    Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are common neurodegenerative disorders of the aging population, characterized by progressive and abnormal accumulation of α-synuclein (α-syn). Recent studies have shown that C-terminus (CT) truncation and propagation of α-syn play a role in the pathogenesis of PD/DLB. Therefore, we explored the effect of passive immunization against the CT of α-syn in the mThy1-α-syn transgenic (tg) mouse model, which resembles the striato-nigral and motor deficits of PD. Mice were immunized with the new monoclonal antibodies 1H7, 5C1, or 5D12, all directed against the CT of α-syn. CT α-syn antibodies attenuated synaptic and axonal pathology, reduced the accumulation of CT-truncated α-syn (CT-α-syn) in axons, rescued the loss of tyrosine hydroxylase fibers in striatum, and improved motor and memory deficits. Among them, 1H7 and 5C1 were most effective at decreasing levels of CT-α-syn and higher-molecular-weight aggregates. Furthermore, in vitro studies showed that preincubation of recombinant α-syn with 1H7 and 5C1 prevented CT cleavage of α-syn. In a cell-based system, CT antibodies reduced cell-to-cell propagation of full-length α-syn, but not of the CT-α-syn that lacked the 118-126 aa recognition site needed for antibody binding. Furthermore, the results obtained after lentiviral expression of α-syn suggest that antibodies might be blocking the extracellular truncation of α-syn by calpain-1. Together, these results demonstrate that antibodies against the CT of α-syn reduce levels of CT-truncated fragments of the protein and its propagation, thus ameliorating PD-like pathology and improving behavioral and motor functions in a mouse model of this disease. Copyright © 2014 the authors 0270-6474/14/349441-14$15.00/0.

  11. Pyrethroids and DDT tolerance of Anopheles gambiae s.l. from Sengerema District, an area of intensive pesticide usage in north-western Tanzania.

    Science.gov (United States)

    Philbert, Anitha; Lyantagaye, Sylvester Leonard; Pradel, Gabriele; Ngwa, Che Julius; Nkwengulila, Gamba

    2017-04-01

    To assess the susceptibility status of malaria vectors to pyrethroids and dichlorodiphenyltrichloroethane (DDT), characterise the mechanisms underlying resistance and evaluate the role of agro-chemical use in resistance selection among malaria vectors in Sengerema agro-ecosystem zone, Tanzania. Mosquito larvae were collected from farms and reared to obtain adults. The susceptibility status of An. gambiae s.l. was assessed using WHO bioassay tests to permethrin, deltamethrin, lambdacyhalothrin, etofenprox, cyfluthrin and DDT. Resistant specimens were screened for knock-down resistance gene (kdr), followed by sequencing both Western and Eastern African variants. A gas chromatography-mass spectrophotometer (GC-MS) was used to determine pesticide residues in soil and sediments from mosquitoes' breeding habitats. Anopheles gambiae s.l. was resistant to all the insecticides tested. The population of Anopheles gambiae s.l was composed of Anopheles arabiensis by 91%. The East African kdr (L1014S) allele was found in 13 of 305 specimens that survived insecticide exposure, with an allele frequency from 0.9% to 50%. DDTs residues were found in soils at a concentration up to 9.90 ng/g (dry weight). The observed high resistance levels of An. gambiae s.l., the detection of kdr mutations and pesticide residues in mosquito breeding habitats demonstrate vector resistance mediated by pesticide usage. An integrated intervention through collaboration of agricultural, livestock and vector control units is vital. © 2017 John Wiley & Sons Ltd.

  12. Multivariate density estimation using dimension reducing information and tail flattening transformations for truncated or censored data

    DEFF Research Database (Denmark)

    Buch-Kromann, Tine; Nielsen, Jens

    2012-01-01

    This paper introduces a multivariate density estimator for truncated and censored data with special emphasis on extreme values based on survival analysis. A local constant density estimator is considered. We extend this estimator by means of tail flattening transformation, dimension reducing prior...

  13. Use of the truncated shifted Pareto distribution in assessing size distribution of oil and gas fields

    Science.gov (United States)

    Houghton, J.C.

    1988-01-01

    The truncated shifted Pareto (TSP) distribution, a variant of the two-parameter Pareto distribution, in which one parameter is added to shift the distribution right and left and the right-hand side is truncated, is used to model size distributions of oil and gas fields for resource assessment. Assumptions about limits to the left-hand and right-hand side reduce the number of parameters to two. The TSP distribution has advantages over the more customary lognormal distribution because it has a simple analytic expression, allowing exact computation of several statistics of interest, has a "J-shape," and has more flexibility in the thickness of the right-hand tail. Oil field sizes from the Minnelusa play in the Powder River Basin, Wyoming and Montana, are used as a case study. Probability plotting procedures allow easy visualization of the fit and help the assessment. ?? 1988 International Association for Mathematical Geology.

  14. Restoration of uridine 5′-triphosphate-suppressed delayed rectifying K+ currents by an NO activator KMUP-1 involves RhoA/Rho kinase signaling in pulmonary artery smooth muscle cells

    Directory of Open Access Journals (Sweden)

    Zen-Kong Dai

    2016-12-01

    Full Text Available We have demonstrated that KMUP-1 (7-[2-[4-(2-chlorobenzenepiperazinyl]ethyl]-1,3-dimethylxanthine blunts monocrotaline-induced pulmonary arterial hypertension by altering Ca2+ sensitivity, K+-channel function, endothelial nitric oxide synthase activity, and RhoA/Rho kinase (ROCK expression. This study further investigated whether KMUP-1 impedes uridine 5′-triphosphate (UTP-inhibited delayed rectifying K+ (KDR current in rat pulmonary arteries involved the RhoA/ROCK signaling. Pulmonary artery smooth muscle cells (PASMCs were enzymatically dissociated from rat pulmonary arteries. KMUP-1 (30μM attenuated UTP (30μM-mediated membrane depolarization and abolished UTP-enhanced cytosolic Ca2+ concentration. Whole-cell patch-clamp electrophysiology was used to monitor KDR currents. A voltage-dependent KDR current was isolated and shown to consist of a 4-aminopyridine (5mM-sensitive component and an insensitive component. The 4-aminopyridine sensitive KDR current was suppressed by UTP (30μM. The ROCK inhibitor Y27632 (30μM abolished the ability of UTP to inhibit the KDR current. Like Y27632, KMUP-1 (30μM similarly abolished UTP-inhibited KDR currents. Superfused protein kinase A and protein kinase G inhibitors (KT5720, 300nM and KT5823, 300nM did not affect UTP-inhibited KDR currents, but the currents were restored by adding KMUP-1 (30μM to the superfusate. KMUP-1 reversal of KDR current inhibition by UTP predominantly involves the ROCK inhibition. The results indicate that the RhoA/ROCK signaling pathway plays a key role in eliciting PASMCs depolarization caused by UTP, which would result in pulmonary artery constriction. KMUP-1 blocks UTP-mediated PASMCs depolarization, suggesting that it would prevent abnormal pulmonary vasoconstriction.

  15. Subclinical pregnancy toxemia induced gene expression changes in ovine placenta and uterus

    Directory of Open Access Journals (Sweden)

    Ramanathan K Kasimanickam

    2016-08-01

    Full Text Available The objective was to elucidate gene expression differences in uterus, caruncle and cotyledon of ewes with subclinical pregnancy toxemia (SCPT and healthy ewes, and to identify associated biological functions and pathways involved in pregnancy toxemia. On Day 136 (±1 day post breeding ewes (n=18 had body condition score (BCS; 1 to 5; 1, emaciated; 5, obese assessed and blood samples were collected for plasma glucose and β-hydroxybutyrate (BHBA analyses. The ewes were euthanized and tissue samples were collected from the gravid uterus and placentomes. Based on BCS (2.0 ± 0.02, glucose (2.4 ± 0.33 and BHBA (0.97 ± 0.06 concentrations, ewes (n=10 were grouped as healthy (n=5 and subclinical SCPT (n=5 ewes. The mRNA expressions were determined by quantitative PCR method and prediction of miRNA partners and target genes for the predicted miRNA were identified using miRDB (http://mirdb.org/miRDB/. Top ranked target genes were used to identify associated biological functions and pathways in response to subclinical pregnancy toxemia using PANTHER. The angiogenesis genes VEGF and PlGF, and AdipoQ, AdipoR2, PPARG, LEP, IGF1, IGF2, IL1b and TNFα mRNA expressions were lower in abundances; whereas hypoxia genes eNOS, HIF1a, and HIF 2a, and sFlt1 and KDR mRNA expressions were greater in abundances in uterus and placenta of SCPT ewes compared to healthy ewes (P<0.05. The predicted miRNA and associated target genes contributed to several biological processes, including apoptosis, biological adhesion, biological regulation, cellular component biogenesis, cellular process, developmental process, immune system process, localization, metabolic process, multicellular organismal process, reproduction, and response to stimulus. The target genes were involved in several pathways including angiogenesis, cytoskeletal regulation, hypoxia response via HIF activation, interleukin signaling, ubiquitin proteasome and VEGF signaling pathway. In conclusion, genes

  16. The polyproline site in hinge 2 influences the functional capacity of truncated dystrophins.

    Directory of Open Access Journals (Sweden)

    Glen B Banks

    2010-05-01

    Full Text Available Mutations in dystrophin can lead to Duchenne muscular dystrophy or the more mild form of the disease, Becker muscular dystrophy. The hinge 3 region in the rod domain of dystrophin is particularly prone to deletion mutations. In-frame deletions of hinge 3 are predicted to lead to BMD, however the severity of disease can vary considerably. Here we performed extensive structure-function analyses of truncated dystrophins with modified hinges and spectrin-like repeats in mdx mice. We found that the polyproline site in hinge 2 profoundly influences the functional capacity of a microdystrophin(DeltaR4-R23/DeltaCT with a large deletion in the hinge 3 region. Inclusion of polyproline in microdystrophin(DeltaR4-R23/DeltaCT led to small myofibers (12% smaller than wild-type, Achilles myotendinous disruption, ringed fibers, and aberrant neuromuscular junctions in the mdx gastrocnemius muscles. Replacing hinge 2 of microdystrophin(DeltaR4-R23/DeltaCT with hinge 3 significantly improved the functional capacity to prevent muscle degeneration, increase muscle fiber area, and maintain the junctions. We conclude that the rigid alpha-helical structure of the polyproline site significantly impairs the functional capacity of truncated dystrophins to maintain appropriate connections between the cytoskeleton and extracellular matrix.

  17. Comment on the consistency of truncated nonlinear integral equation based theories of freezing

    International Nuclear Information System (INIS)

    Cerjan, C.; Bagchi, B.; Rice, S.A.

    1985-01-01

    We report the results of two studies of aspects of the consistency of truncated nonlinear integral equation based theories of freezing: (i) We show that the self-consistent solutions to these nonlinear equations are unfortunately sensitive to the level of truncation. For the hard sphere system, if the Wertheim--Thiele representation of the pair direct correlation function is used, the inclusion of part but not all of the triplet direct correlation function contribution, as has been common, worsens the predictions considerably. We also show that the convergence of the solutions found, with respect to number of reciprocal lattice vectors kept in the Fourier expansion of the crystal singlet density, is slow. These conclusions imply great sensitivity to the quality of the pair direct correlation function employed in the theory. (ii) We show the direct correlation function based and the pair correlation function based theories of freezing can be cast into a form which requires solution of isomorphous nonlinear integral equations. However, in the pair correlation function theory the usual neglect of the influence of inhomogeneity of the density distribution on the pair correlation function is shown to be inconsistent to the lowest order in the change of density on freezing, and to lead to erroneous predictions

  18. On the Analytical and Numerical Properties of the Truncated Laplace Transform

    Science.gov (United States)

    2014-05-01

    classical study of the truncated Fourier trans- form. The resulting algorithms are applicable to all environments likely to be encountered in applications...other words, (((La,b)∗ ◦ La,b) (un)) (t) = ∫ b a 1 t+ s un(s)ds = α 2 nun (t). (2.69) Observation 2.22. Similarly, La,b ◦ (La,b)∗ of a function g ∈ L2(0...3.20)) are even and odd functions in the regular sense: Un(s) = (Cγ(un)) (s) = (−1) nUn (−s). (3.25) In particular, at the point s = 0, we have: U2j+1(0

  19. Analysis and design of optimized truncated scarfed nozzles subject to external flow effects

    Science.gov (United States)

    Shyne, Rickey J.; Keith, Theo G., Jr.

    1990-01-01

    Rao's method for computing optimum thrust nozzles is modified to study the effects of external flow on the performance of a class of exhaust nozzles. Members of this class are termed scarfed nozzles. These are two-dimensional, nonsymmetric nozzles with a flat lower wall. The lower wall (the cowl) is truncated in order to save weight. Results from a parametric investigation are presented to show the effects of the external flowfield on performance.

  20. Cross-layer designed adaptive modulation algorithm with packet combining and truncated ARQ over MIMO Nakagami fading channels

    KAUST Repository

    Aniba, Ghassane; Aissa, Sonia

    2011-01-01

    works addressed the link layer performance of AM with truncated ARQ but without packet combining. In addition, previously proposed AM algorithms are not optimal and can provide poor performance when packet combining is implemented. Herein, we first show

  1. Ptychographic x-ray imaging of surfaces on crystal truncation rod

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Chenhui; Barbour, Andi; Liu, Yaohua; You, Hoydoo, E-mail: hyou@anl.gov [Materials Science Division, Argonne National Laboratory, Argonne, Illinois 60439 (United States); Harder, Ross; Xu, Ruqing [Advanced Photon Source, Argonne National Laboratory, Argonne, Illinois 60439 (United States); Diaz, Ana; Menzel, Andreas [Paul Scherrer Institut, Villigen PSI 5232 (Switzerland); Komanicky, Vladimir [Faculty of Sciences, Safarik University, Kosice 04154 (Slovakia); Huang, Xiaojing [National Synchrotron Light Source II, Brookhaven National Laboratory, Upton, New York 11973 (United States); Pierce, Michael S. [School of Physics and Astronomy, Rochester Institute of Technology, Rochester, New York 14623 (United States)

    2015-03-09

    Ptychography is a high-resolution imaging technique, which does not require lenses for image magnification and which provides phase contrast with high sensitivity. Here, we propose to use x-ray ptychography for the imaging of surface structure in crystalline samples. We show that ptychography can be used to image atomic step structures using coherent diffraction patterns recorded along the crystal truncation rod of a crystal surface. In a proof-of-concept experiment on a Pt (111) sample, we present ptychographic reconstructions showing features consistent with surface steps. Due to the penetration power of x-rays, this method could find interesting applications for the study of surface structures under buried interfaces or in harsh environments.

  2. Ptychographic x-ray imaging of surfaces on crystal truncation rod

    International Nuclear Information System (INIS)

    Zhu, Chenhui; Barbour, Andi; Liu, Yaohua; You, Hoydoo; Harder, Ross; Xu, Ruqing; Diaz, Ana; Menzel, Andreas; Komanicky, Vladimir; Huang, Xiaojing; Pierce, Michael S.

    2015-01-01

    Ptychography is a high-resolution imaging technique, which does not require lenses for image magnification and which provides phase contrast with high sensitivity. Here, we propose to use x-ray ptychography for the imaging of surface structure in crystalline samples. We show that ptychography can be used to image atomic step structures using coherent diffraction patterns recorded along the crystal truncation rod of a crystal surface. In a proof-of-concept experiment on a Pt (111) sample, we present ptychographic reconstructions showing features consistent with surface steps. Due to the penetration power of x-rays, this method could find interesting applications for the study of surface structures under buried interfaces or in harsh environments

  3. Non-perturbative Calculation of the Scalar Yukawa Theory in Four-Body Truncation

    International Nuclear Information System (INIS)

    Li, Yang; Maris, P.; Vary, J. P.; Karmanov, V. A.

    2015-01-01

    The quenched scalar Yukawa theory is solved in the light-front Tamm–Dancoff approach including up to four constituents (one scalar nucleon, three scalar pions). The Fock sector dependent renormalization is implemented. By studying the Fock sector norms, we find that the lowest two Fock sectors dominate the state even in the large-coupling region. The one-body sector shows convergence with respect to the Fock sector truncation. However, the four-body norm exceeds the three-body norm at the coupling α≈1.7 . (author)

  4. A new alternative transcript encodes a 60 kDa truncated form of integrin beta 3.

    Science.gov (United States)

    Djaffar, I; Chen, Y P; Creminon, C; Maclouf, J; Cieutat, A M; Gayet, O; Rosa, J P

    1994-05-15

    A cDNA for integrin beta 3 isolated from a human erythroleukaemia (HEL) cell library contained a 340 bp insert at position 1281. This mRNA, termed beta 3c, results from the use of a cryptic AG donor splice site in intron 8 of the beta 3 gene, and is different from a previously described alternative beta 3 mRNA. The predicted open reading frame of beta 3C stops at a TAG stop codon 69 bp downstream from position 1281. It starts with the signal peptide and the 404 N-terminal extracellular residues of beta 3, encompassing the ligand binding sites, followed by 23 C-terminal intron-derived residues, corresponding to a truncated form of beta 3 lacking the cysteine-rich, transmembrane and cytoplasmic domains. Expression of beta 3C mRNA was demonstrated in human platelets, megakaryocytes, endothelial cells and HEL cells by reverse transcriptase/PCR. The beta 3C transcript was also demonstrated in the mouse, suggesting its conservation through evolution. Finally, a 60 kDa polypeptide corresponding to the beta 3C alternative transcript was demonstrated in platelets by Western blotting using a polyclonal antibody raised against a synthetic peptide designed from the beta 3C intronic sequence. Taken together, these results suggest a biological role for beta 3C, the first alternative transcript showing an altered extracellular domain of a beta integrin.

  5. Performance Analysis of Thermoelectric Modules Consisting of Square Truncated Pyramid Elements Under Constant Heat Flux

    Science.gov (United States)

    Oki, Sae; Natsui, Shungo; Suzuki, Ryosuke O.

    2018-06-01

    System design of a thermoelectric (TE) power generation module is pursued in order to improve the TE performance. Square truncated pyramid shaped P-N pairs of TE elements are connected electronically in series in the open space between two flat insulator boards. The performance of the TE module consisting of 2-paired elements is numerically simulated using commercial software and original TE programs. Assuming that the heat radiating into the hot surface is regulated, i.e., the amount of heat from the hot surface to the cold one is steadily constant, as it happens for solar radiation heating, the performance is significantly improved by changing the shape and the alignment pattern of the elements. When the angle θ between the edge and the base is smaller than 72°, and when the cold surface is kept at a constant temperature, two patterns in particular, amongst the 17 studied, show the largest TE power and efficiency. In comparison to other geometries, the smarter square truncated pyramid shape can provide higher performance using a large cold bath and constant heat transfer by heat radiation.

  6. Impact of improved attenuation correction featuring a bone atlas and truncation correction on PET quantification in whole-body PET/MR.

    Science.gov (United States)

    Oehmigen, Mark; Lindemann, Maike E; Gratz, Marcel; Kirchner, Julian; Ruhlmann, Verena; Umutlu, Lale; Blumhagen, Jan Ole; Fenchel, Matthias; Quick, Harald H

    2018-04-01

    Recent studies have shown an excellent correlation between PET/MR and PET/CT hybrid imaging in detecting lesions. However, a systematic underestimation of PET quantification in PET/MR has been observed. This is attributable to two methodological challenges of MR-based attenuation correction (AC): (1) lack of bone information, and (2) truncation of the MR-based AC maps (μmaps) along the patient arms. The aim of this study was to evaluate the impact of improved AC featuring a bone atlas and truncation correction on PET quantification in whole-body PET/MR. The MR-based Dixon method provides four-compartment μmaps (background air, lungs, fat, soft tissue) which served as a reference for PET/MR AC in this study. A model-based bone atlas provided bone tissue as a fifth compartment, while the HUGE method provided truncation correction. The study population comprised 51 patients with oncological diseases, all of whom underwent a whole-body PET/MR examination. Each whole-body PET dataset was reconstructed four times using standard four-compartment μmaps, five-compartment μmaps, four-compartment μmaps + HUGE, and five-compartment μmaps + HUGE. The SUV max for each lesion was measured to assess the impact of each μmap on PET quantification. All four μmaps in each patient provided robust results for reconstruction of the AC PET data. Overall, SUV max was quantified in 99 tumours and lesions. Compared to the reference four-compartment μmap, the mean SUV max of all 99 lesions increased by 1.4 ± 2.5% when bone was added, by 2.1 ± 3.5% when HUGE was added, and by 4.4 ± 5.7% when bone + HUGE was added. Larger quantification bias of up to 35% was found for single lesions when bone and truncation correction were added to the μmaps, depending on their individual location in the body. The novel AC method, featuring a bone model and truncation correction, improved PET quantification in whole-body PET/MR imaging. Short reconstruction times, straightforward

  7. Impact of improved attenuation correction featuring a bone atlas and truncation correction on PET quantification in whole-body PET/MR

    Energy Technology Data Exchange (ETDEWEB)

    Oehmigen, Mark; Lindemann, Maike E. [University Hospital Essen, High Field and Hybrid MR Imaging, Essen (Germany); Gratz, Marcel; Quick, Harald H. [University Hospital Essen, High Field and Hybrid MR Imaging, Essen (Germany); University Duisburg-Essen, Erwin L. Hahn Institute for MR Imaging, Essen (Germany); Kirchner, Julian [University Dusseldorf, Department of Diagnostic and Interventional Radiology, Medical Faculty, Dusseldorf (Germany); Ruhlmann, Verena [University Hospital Essen, Department of Nuclear Medicine, Essen (Germany); Umutlu, Lale [University Hospital Essen, Department of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); Blumhagen, Jan Ole; Fenchel, Matthias [Siemens Healthcare GmbH, Erlangen (Germany)

    2018-04-15

    Recent studies have shown an excellent correlation between PET/MR and PET/CT hybrid imaging in detecting lesions. However, a systematic underestimation of PET quantification in PET/MR has been observed. This is attributable to two methodological challenges of MR-based attenuation correction (AC): (1) lack of bone information, and (2) truncation of the MR-based AC maps (μmaps) along the patient arms. The aim of this study was to evaluate the impact of improved AC featuring a bone atlas and truncation correction on PET quantification in whole-body PET/MR. The MR-based Dixon method provides four-compartment μmaps (background air, lungs, fat, soft tissue) which served as a reference for PET/MR AC in this study. A model-based bone atlas provided bone tissue as a fifth compartment, while the HUGE method provided truncation correction. The study population comprised 51 patients with oncological diseases, all of whom underwent a whole-body PET/MR examination. Each whole-body PET dataset was reconstructed four times using standard four-compartment μmaps, five-compartment μmaps, four-compartment μmaps + HUGE, and five-compartment μmaps + HUGE. The SUV{sub max} for each lesion was measured to assess the impact of each μmap on PET quantification. All four μmaps in each patient provided robust results for reconstruction of the AC PET data. Overall, SUV{sub max} was quantified in 99 tumours and lesions. Compared to the reference four-compartment μmap, the mean SUV{sub max} of all 99 lesions increased by 1.4 ± 2.5% when bone was added, by 2.1 ± 3.5% when HUGE was added, and by 4.4 ± 5.7% when bone + HUGE was added. Larger quantification bias of up to 35% was found for single lesions when bone and truncation correction were added to the μmaps, depending on their individual location in the body. The novel AC method, featuring a bone model and truncation correction, improved PET quantification in whole-body PET/MR imaging. Short reconstruction times, straightforward

  8. Prediction of the moments in advection-diffusion lattice Boltzmann method. I. Truncation dispersion, skewness, and kurtosis

    Science.gov (United States)

    Ginzburg, Irina

    2017-01-01

    The effect of the heterogeneity in the soil structure or the nonuniformity of the velocity field on the modeled resident time distribution (RTD) and breakthrough curves is quantified by their moments. While the first moment provides the effective velocity, the second moment is related to the longitudinal dispersion coefficient (kT) in the developed Taylor regime; the third and fourth moments are characterized by their normalized values skewness (Sk) and kurtosis (Ku), respectively. The purpose of this investigation is to examine the role of the truncation corrections of the numerical scheme in kT, Sk, and Ku because of their interference with the second moment, in the form of the numerical dispersion, and in the higher-order moments, by their definition. Our symbolic procedure is based on the recently proposed extended method of moments (EMM). Originally, the EMM restores any-order physical moments of the RTD or averaged distributions assuming that the solute concentration obeys the advection-diffusion equation in multidimensional steady-state velocity field, in streamwise-periodic heterogeneous structure. In our work, the EMM is generalized to the fourth-order-accurate apparent mass-conservation equation in two- and three-dimensional duct flows. The method looks for the solution of the transport equation as the product of a long harmonic wave and a spatially periodic oscillating component; the moments of the given numerical scheme are derived from a chain of the steady-state fourth-order equations at a single cell. This mathematical technique is exemplified for the truncation terms of the two-relaxation-time lattice Boltzmann scheme, using plug and parabolic flow in straight channel and cylindrical capillary with the d2Q9 and d3Q15 discrete velocity sets as simple but illustrative examples. The derived symbolic dependencies can be readily extended for advection by another, Newtonian or non-Newtonian, flow profile in any-shape open-tabular conduits. It is

  9. Construction of occluded recombinant baculoviruses containing the full-length cry1Ab and cry1Ac genes from Bacillus thuringiensis

    Directory of Open Access Journals (Sweden)

    B.M. Ribeiro

    1998-06-01

    Full Text Available The administration of baculoviruses to insects for bioassay purposes is carried out, in most cases, by contamination of food surfaces with a known amount of occlusion bodies (OBs. Since per os infection is the natural route of infection, occluded recombinant viruses containing crystal protein genes (cry1Ab and cry1Ac from Bacillus thuringiensis were constructed for comparison with the baculovirus prototype Autographa californica nucleopolyhedrovirus (AcNPV. The transfer vector pAcUW2B was used for construction of occluded recombinant viruses. The transfer vector containing the crystal protein genes was cotransfected with linearized DNA from a non-occluded recombinant virus. The isolation of recombinant viruses was greatly facilitated by the reduction of background "wild type" virus and the increased proportion of recombinant viruses. Since the recombinant viruses containing full-length and truncated forms of the crystal protein genes did not seem to improve the pathogenicity of the recombinant viruses when compared with the wild type AcNPV, and in order to compare expression levels of the full-length crystal proteins produced by non-occluded and occluded recombinant viruses the full-length cry1Ab and cry1Ac genes were chosen for construction of occluded recombinant viruses. The recombinant viruses containing full-length and truncated forms of the crystal protein genes did not seem to improve its pathogenicity but the size of the larvae infected with the recombinant viruses was significantly smaller than that of larvae infected with the wild type virus.

  10. Novel and recurrent non-truncating mutations of the MITF basic domain: genotypic and phenotypic variations in Waardenburg and Tietz syndromes

    Science.gov (United States)

    Léger, Sandy; Balguerie, Xavier; Goldenberg, Alice; Drouin-Garraud, Valérie; Cabot, Annick; Amstutz-Montadert, Isabelle; Young, Paul; Joly, Pascal; Bodereau, Virginie; Holder-Espinasse, Muriel; Jamieson, Robyn V; Krause, Amanda; Chen, Hongsheng; Baumann, Clarisse; Nunes, Luis; Dollfus, Hélène; Goossens, Michel; Pingault, Véronique

    2012-01-01

    The microphthalmia-associated transcription factor (MITF) is a basic helix-loop-helix leucine zipper transcription factor, which regulates melanocyte development and the biosynthetic melanin pathway. A notable relationship has been described between non-truncating mutations of its basic domain and Tietz syndrome, which is characterized by albinoid-like hypopigmentation of the skin and hair, rather than the patchy depigmentation seen in Waardenburg syndrome, and severe hearing loss. Twelve patients with new or recurrent non-truncating mutations of the MITF basic domain from six families were enrolled in this study. We observed a wide range of phenotypes and some unexpected features. All the patients had blue irides and pigmentation abnormalities that ranged from diffuse hypopigmentation to Waardenburg-like patches. In addition, they showed congenital complete hearing loss, diffuse hypopigmentation of the skin, freckling and ocular abnormalities, more frequently than patients with MITF mutations outside the basic domain. In conclusion, the non-truncating mutations of the basic domain do not always lead to Tietz syndrome but rather to a large range of phenotypes. Sun-exposed freckles are interestingly observed more frequently in Asian populations. This variability argues for the possible interaction with modifier loci. PMID:22258527

  11. Left truncation results in substantial bias of the relation between time-dependent exposures and adverse events

    NARCIS (Netherlands)

    Hazelbag, Christijan M; Klungel, Olaf H; van Staa, Tjeerd P; de Boer, Anthonius; Groenwold, Rolf H H

    PURPOSE: To assess the impact of random left truncation of data on the estimation of time-dependent exposure effects. METHODS: A simulation study was conducted in which the relation between exposure and outcome was based on an immediate exposure effect, a first-time exposure effect, or a cumulative

  12. Left truncation results in substantial bias of the relation between time-dependent exposures and adverse events

    NARCIS (Netherlands)

    Hazelbag, Christijan M.; Klungel, Olaf H.; van Staa, Tjeerd P.; de Boer, Anthonius; Groenwold, Rolf H H

    2015-01-01

    PURPOSE: To assess the impact of random left truncation of data on the estimation of time-dependent exposure effects. METHODS: A simulation study was conducted in which the relation between exposure and outcome was based on an immediate exposure effect, a first-time exposure effect, or a cumulative

  13. Uniform physical theory of diffraction equivalent edge currents for truncated wedge strips

    DEFF Research Database (Denmark)

    Johansen, Peter Meincke

    1996-01-01

    New uniform closed-form expressions for physical theory of diffraction equivalent edge currents are derived for truncated incremental wedge strips. In contrast to previously reported expressions, the new expressions are well behaved for all directions of incidence and observation and take a finite...... value for zero strip length. This means that the expressions are well suited for implementation in general computer codes. The new expressions are expressed as the difference between two terms. The first term is obtained by integrating the exact fringe wave current on a wedge along an untruncated...

  14. Computation of Lie transformations from a power series: Bounds and optimum truncation

    International Nuclear Information System (INIS)

    Gjaja, I.

    1996-01-01

    The problem considered is the computation of an infinite product (composition) of Lie transformations generated by homogeneous polynomials of increasing order from a given asymptotic power series. Bounds are computed for the infinitesimal form of the Lie transformations and for the domain of analyticity of the first n of them. Even when the power series is convergent, the estimates exhibit a factorial-type growth, and thus do not guarantee convergence of the product. The optimum truncation is determined by minimizing the remainder after the first n Lie transformations have been applied

  15. Bioakumulasi Logam Berat oleh Beberapa Galur Bradyrhizobium japonicum

    Directory of Open Access Journals (Sweden)

    ADE NOOR SYAMSUDIN

    2005-09-01

    Full Text Available Heavy metal utilization in industry and agriculture have caused an environmental problem to existing life. Bioaccumulation is made up by a concentration of certain chemical compounds in living tissues. The objective of this research was to reveal the ability of lipopolysaccharides (LPSs of heavy metal Bradyrhizobium japonicum tolerant strains in accumulating heavy metals. The strains used were BDG 10, KDR 10, and KDR 15. The ability of each strains on heavy metal accumulation of Cu, Pb, Zn, Ni, and Cd were quantitatively determined using atomic absorption spectrophotometry. The result showed that each strains has its own capacity to accumulate heavy metals. Accumulation of Cu (0.100, Pb (0.320, and Cd (0.048 ppm/mg dry weight by KDR 10 seem higher than BDG 10 and KDR 15. The highest accumulation of Zn and Ni was shown by KDR 15 in which the value were 0.360 and 0.165 ppm/mg dry weight, respectively and the least accumulation of all heavy metal studied was shown by BDG 10.

  16. Cloning and heterologous expression of the antibiotic peptide (ABP) genes from Rhizopus oligosporus NBRC 8631.

    Science.gov (United States)

    Yamada, Osamu; Sakamoto, Kazutoshi; Tominaga, Mihoko; Nakayama, Tasuku; Koseki, Takuya; Fujita, Akiko; Akita, Osamu

    2005-03-01

    We carried out protein sequencing of purified Antibiotic Peptide (ABP), and cloned two genes encoding this peptide as abp1 and abp2, from Rhizopus oligosporus NBRC 8631. Both genes contain an almost identical 231-bp segment, with only 3 nucleotide substitutions, encoding a 77 amino acid peptide. The abp gene product comprises a 28 amino acid signal sequence and a 49 amino acid mature peptide. Northern blot analysis showed that at least one of the abp genes is transcribed in R. oligosporus NBRC 8631. A truncated form of abp1 encoding only the mature peptide was fused with the alpha-factor signal peptide and engineered for expression in Pichia pastoris SMD1168H. Culture broth of the recombinant Pichia displayed ABP activity against Bacillus subtilis NBRC 3335 after induction of heterologous gene expression. This result indicates that mature ABP formed the active structure without the aid of other factors from R. oligosporus, and was secreted.

  17. Growth and gene expression are predominantly controlled by distinct regions of the human IL-4 receptor.

    Science.gov (United States)

    Ryan, J J; McReynolds, L J; Keegan, A; Wang, L H; Garfein, E; Rothman, P; Nelms, K; Paul, W E

    1996-02-01

    IL-4 causes hematopoietic cells to proliferate and express a series of genes, including CD23. We examined whether IL-4-mediated growth, as measured by 4PS phosphorylation, and gene induction were similarly controlled. Studies of M12.4.1 cells expressing human IL-4R truncation mutants indicated that the region between amino acids 557-657 is necessary for full gene expression, which correlated with Stat6 DNA binding activity. This region was not required for 4PS phosphorylation. Tyrosine-to-phenylalanine mutations in the interval between amino acids 557-657 revealed that as long as one tyrosine remained unmutated, CD23 was fully induced. When all three tyrosines were mutated, the receptor was unable to induce CD23. The results indicate that growth regulation and gene expression are principally controlled by distinct regions of IL-4R.

  18. Generalized Truncated Methods for an Efficient Solution of Retrial Systems

    Directory of Open Access Journals (Sweden)

    Ma Jose Domenech-Benlloch

    2008-01-01

    Full Text Available We are concerned with the analytic solution of multiserver retrial queues including the impatience phenomenon. As there are not closed-form solutions to these systems, approximate methods are required. We propose two different generalized truncated methods to effectively solve this type of systems. The methods proposed are based on the homogenization of the state space beyond a given number of users in the retrial orbit. We compare the proposed methods with the most well-known methods appeared in the literature in a wide range of scenarios. We conclude that the proposed methods generally outperform previous proposals in terms of accuracy for the most common performance parameters used in retrial systems with a moderated growth in the computational cost.

  19. Cap integration in spectral gravity forward modelling: near- and far-zone gravity effects via Molodensky's truncation coefficients

    Science.gov (United States)

    Bucha, Blažej; Hirt, Christian; Kuhn, Michael

    2018-04-01

    Spectral gravity forward modelling is a technique that converts a band-limited topography into its implied gravitational field. This conversion implicitly relies on global integration of topographic masses. In this paper, a modification of the spectral technique is presented that provides gravity effects induced only by the masses located inside or outside a spherical cap centred at the evaluation point. This is achieved by altitude-dependent Molodensky's truncation coefficients, for which we provide infinite series expansions and recurrence relations with a fixed number of terms. Both representations are generalized for an arbitrary integer power of the topography and arbitrary radial derivative. Because of the altitude-dependency of the truncation coefficients, a straightforward synthesis of the near- and far-zone gravity effects at dense grids on irregular surfaces (e.g. the Earth's topography) is computationally extremely demanding. However, we show that this task can be efficiently performed using an analytical continuation based on the gradient approach, provided that formulae for radial derivatives of the truncation coefficients are available. To demonstrate the new cap-modified spectral technique, we forward model the Earth's degree-360 topography, obtaining near- and far-zone effects on gravity disturbances expanded up to degree 3600. The computation is carried out on the Earth's surface and the results are validated against an independent spatial-domain Newtonian integration (1 μGal RMS agreement). The new technique is expected to assist in mitigating the spectral filter problem of residual terrain modelling and in the efficient construction of full-scale global gravity maps of highest spatial resolution.

  20. A targeted constitutive mutation in the APC tumor suppressor gene underlies mammary but not intestinal tumorigenesis.

    Directory of Open Access Journals (Sweden)

    Claudia Gaspar

    2009-07-01

    Full Text Available Germline mutations in the adenomatous polyposis coli (APC gene are responsible for familial adenomatous polyposis (FAP, an autosomal dominant hereditary predisposition to the development of multiple colorectal adenomas and of a broad spectrum of extra-intestinal tumors. Moreover, somatic APC mutations play a rate-limiting and initiating role in the majority of sporadic colorectal cancers. Notwithstanding its multifunctional nature, the main tumor suppressing activity of the APC gene resides in its ability to regulate Wnt/beta-catenin signaling. Notably, genotype-phenotype correlations have been established at the APC gene between the length and stability of the truncated proteins encoded by different mutant alleles, the corresponding levels of Wnt/beta-catenin signaling activity they encode for, and the incidence and distribution of intestinal and extra-intestinal tumors. Here, we report a novel mouse model, Apc1572T, obtained by targeting a truncated mutation at codon 1572 in the endogenous Apc gene. This hypomorphic mutant allele results in intermediate levels of Wnt/beta-catenin signaling activation when compared with other Apc mutations associated with multifocal intestinal tumors. Notwithstanding the constitutive nature of the mutation, Apc(+/1572T mice have no predisposition to intestinal cancer but develop multifocal mammary adenocarcinomas and subsequent pulmonary metastases in both genders. The histology of the Apc1572T primary mammary tumours is highly heterogeneous with luminal, myoepithelial, and squamous lineages and is reminiscent of metaplastic carcinoma of the breast in humans. The striking phenotype of Apc(+/1572T mice suggests that specific dosages of Wnt/beta-catenin signaling activity differentially affect tissue homeostasis and initiate tumorigenesis in an organ-specific fashion.

  1. Construction of a recombinant adenovirus co-expressing truncated human prostate-specific membrane antigen and mouse 4-1BBL genes and its effect on dendritic cells

    Directory of Open Access Journals (Sweden)

    Xiaodong Weng

    2011-03-01

    Full Text Available Our aim was to construct a recombinant adenovirus co-expressing truncated human prostate-specific membrane antigen (tPSMA and mouse 4-1BBL genes and to determine its effect on dendritic cells (DCs generated from bone marrow suspensions harvested from C57BL/6 mice for which the effect of 4-1BBL on DCs is not clear, especially during DCs processing tumor-associated antigen. Replication deficient adenovirus AdMaxTM Expression System was used to construct recombinant adenovirus Ad-tPSMA-internal ribosome entry site-mouse 4-1BBL (Ad-tPSMA-IRES-m4-1BBL and Ad-enhanced green fluorescent protein. Day 7 proliferating DC aggregates generated from C57BL/6 mice were collected as immature DCs and further mature DCs were obtained by lipopolysaccharide activated immature DCs. After DCs were exposed to the recombinant adenovirus with 250 multiplicity of infection, the expression of tPSMA and m4-1BBL proteins were detected by Western blot, and the apoptosis and phenotype of DCs were analyzed by flow cytometry. Cytokines (IL-6 and IL-12 in the supernatant were detected by enzyme-linked immunosorbent assay (ELISA. Proliferation of T cells was detected by allogeneic mixed lymphocyte reactions. The tPSMA and m4-1BBL proteins were expressed correctly. The apoptosis rate of DCs transfected with Ad-tPSMA-IRES-m4-1BBL was 14.6%, lower than that of control DCs. The expression of co-stimulatory molecules [CD80 (81.6 ± 5.4% and CD86 (80.13 ± 2.81%] up-regulated in Ad-tPSMA-IRES-m4-1BBL-pulsed DCs, and the level of IL-6 (3960.2 ± 50.54 pg/mL and IL-12 (249.57 ± 12.51 pg/mL production in Ad-tPSMA-IRES-m4-1BBL-transduced DCs were significantly higher (P < 0.05 than those in control DCs. Ad-tPSMA-IRES-m4-1BBL induced higher T-cell proliferation (OD450 = 0.614 ± 0.018, indicating that this recombinant adenovirus can effectively enhance the activity of DCs.

  2. Circulating progenitor and angiogenic cell frequencies are abnormally static over pregnancy in women with preconception diabetes: A pilot study.

    Science.gov (United States)

    Lima, Patricia D A; Chen, Zhilin; Tayab, Aysha; Murphy, Malia S Q; Pudwell, Jessica; Smith, Graeme N; Croy, B Anne

    2017-01-01

    Type 1 and 2 diabetes decrease the frequencies and functional capacities of circulating angiogenic cells (CAC). Diabetes also elevates gestational complications. These observations may be interrelated. We undertook pilot studies to address the hypothesis that preconception diabetes deviates known gestational increases in CACs. Cross-sectional study of type 1 diabetic, type 2 diabetic and normoglycemic pregnant women was conducted at 1st, 2nd, and 3rd trimester and compared to a 6mo postpartum surrogate baseline. Circulating progenitor cells (CPC; CD34+CD45dimSSlow) and CACs (CD34+CD45dimSSlow expressing CD133 without or with KDR) were quantified by flow cytometry and by colony assay (CFU-Hill). In pregnant normoglycemic women, CD34+CD45dimSSlow cell frequency was greater in 1st and 3rd trimester than postpartum but frequency of these cells was static over type 1 or 2 diabetic pregnancies. Type 1 and type 2 diabetic women showed CACs variance versus normal controls. Type 1 diabetic women had more total CD34+KDR+ CACs in 1st trimester and a higher ratio of CD133+KDR+ to total CD133+ cells in 1st and 2nd trimesters than control women, demonstrating an unbalance in CD133+KDR+ CACs. Type 2 diabetic women had more CD133+KDR+ CACs in 1st trimester and fewer CD133+KDR- CACs at mid-late pregnancy than normal pregnant women. Thus, pregnancy stage-specific physiological fluctuation in CPCs (CD34+) and CACs (CD133+KDR+ and CD133+KDR-) did not occur in type 1 and type 2 diabetic women. Early outgrowth colonies were stable across normal and diabetic pregnancies. Therefore, preconception diabetes blocks the normal dynamic pattern of CAC frequencies across gestation but does not alter colony growth. The differences between diabetic and typical women were seen at specific gestational stages that may be critical for initiation of the uterine vascular pathologies characterizing diabetic gestations.

  3. Circulating progenitor and angiogenic cell frequencies are abnormally static over pregnancy in women with preconception diabetes: A pilot study.

    Directory of Open Access Journals (Sweden)

    Patricia D A Lima

    Full Text Available Type 1 and 2 diabetes decrease the frequencies and functional capacities of circulating angiogenic cells (CAC. Diabetes also elevates gestational complications. These observations may be interrelated. We undertook pilot studies to address the hypothesis that preconception diabetes deviates known gestational increases in CACs. Cross-sectional study of type 1 diabetic, type 2 diabetic and normoglycemic pregnant women was conducted at 1st, 2nd, and 3rd trimester and compared to a 6mo postpartum surrogate baseline. Circulating progenitor cells (CPC; CD34+CD45dimSSlow and CACs (CD34+CD45dimSSlow expressing CD133 without or with KDR were quantified by flow cytometry and by colony assay (CFU-Hill. In pregnant normoglycemic women, CD34+CD45dimSSlow cell frequency was greater in 1st and 3rd trimester than postpartum but frequency of these cells was static over type 1 or 2 diabetic pregnancies. Type 1 and type 2 diabetic women showed CACs variance versus normal controls. Type 1 diabetic women had more total CD34+KDR+ CACs in 1st trimester and a higher ratio of CD133+KDR+ to total CD133+ cells in 1st and 2nd trimesters than control women, demonstrating an unbalance in CD133+KDR+ CACs. Type 2 diabetic women had more CD133+KDR+ CACs in 1st trimester and fewer CD133+KDR- CACs at mid-late pregnancy than normal pregnant women. Thus, pregnancy stage-specific physiological fluctuation in CPCs (CD34+ and CACs (CD133+KDR+ and CD133+KDR- did not occur in type 1 and type 2 diabetic women. Early outgrowth colonies were stable across normal and diabetic pregnancies. Therefore, preconception diabetes blocks the normal dynamic pattern of CAC frequencies across gestation but does not alter colony growth. The differences between diabetic and typical women were seen at specific gestational stages that may be critical for initiation of the uterine vascular pathologies characterizing diabetic gestations.

  4. Adenovirus-mediated truncated Bid overexpression induced by the Cre/LoxP system promotes the cell apoptosis of CD133+ ovarian cancer stem cells.

    Science.gov (United States)

    Long, Qifang; Yang, Ru; Lu, Weixian; Zhu, Weipei; Zhou, Jundong; Zheng, Cui; Zhou, Dongmei; Yu, Ling; Wu, Jinchang

    2017-01-01

    Cancer stem cells are a small subset of cancer cells that contribute to cancer progression, metastasis, chemoresistance and recurrence. CD133-positive (CD133+) ovarian cancer cells have been identified as ovarian cancer stem cells. Adenovirus-mediated gene therapy is an innovative therapeutic method for cancer treatment. In the present study, we aimed to develop a new gene therapy to specifically eliminate CD133+ ovarian cancer stem cells by targeting CD133. We used the Cre/LoxP system to augment the selective expression of the truncated Bid (tBid) gene as suicide gene therapy in CD133+ ovarian cancer stem cells. The adenovirus (Ad)-CD133-Cre expressing Cre recombinase under the control of the CD133 promoter and Ad-CMV-LoxP-Neo-LoxP-tBid expressing tBid under the control of the CMV promoter were successfully constructed using the Cre/LoxP switching system. The co-infection of Ad-CMV-LoxP-Neo-LoxP-tBid and Ad-CD133-Cre selectively induced tBid overexpression, which inhibited cell growth and triggered the cell apoptosis of CD133+ ovarian cancer stem cells. The Cre/LoxP system-mediated tBid overexpression activated the pro-apoptotic signaling pathway and augmented the cytotoxic effect of cisplatin in CD133+ ovarian cancer stem cells. Furthermore, in xenograft experiments, co-infection with the two recombinant adenoviruses markedly suppressed tumor growth in vivo and promoted cell apoptosis in tumor tissues. Taken together, the present study provides evidence that the adenovirus-mediated tBid overexpression induced by the Cre/LoxP system can effectively eliminate CD133+ ovarian cancer stem cells, representing a novel therapeutic strategy for the treatment of ovarian cancer.

  5. Improved catalytic efficiency, thermophilicity, anti-salt and detergent tolerance of keratinase KerSMD by partially truncation of PPC domain.

    Science.gov (United States)

    Fang, Zhen; Zhang, Juan; Du, Guocheng; Chen, Jian

    2016-06-14

    The keratinase from Stenotrophomonas maltophilia (KerSMD) is known for its high activity and pH stability in keratin degradation. However, catalytic efficiency and detergent tolerability need to be improved in order to be used for industrial application. In this work, we obtained several keratinase variants with enhanced catalytic efficiency, thermophilicity, and anti-salt and detergent tolerability by partially truncating the PPC domain of KerSMD. The variants all showed improved catalytic efficiency to synthetic substrate AAPF, with the V355 variant having the highest kcat /Km value of 143.6 s(-1) mM(-1). The truncation of keratinase had little effect on alkaline stability but obviously decreased collagenase activity, developing its potential application in leather treatment. The variants V380, V370, and V355 were thermophilic, with a 1.7-fold enhancement of keratinlytic activity at 60 °C when compared to the wild type. The entire truncation of PPC domain obtained the variant V355 with improved tolerance to alkalinity, salt, chaotropic agents, and detergents. The V355 variant showed more than a 40% improvement in activity under 15% (w/v) NaCl or 4% (w/v) SDS solution, showing excellent stability under harsh washing and unhairing conditions. Our work investigated how protein engineering affects the function of PPC domain of KerSMD.

  6. A systems biology analysis of the changes in gene expression via silencing of HPV-18 E1 expression in HeLa cells.

    Science.gov (United States)

    Castillo, Andres; Wang, Lu; Koriyama, Chihaya; Eizuru, Yoshito; Jordan, King; Akiba, Suminori

    2014-10-01

    Previous studies have reported the detection of a truncated E1 mRNA generated from HPV-18 in HeLa cells. Although it is unclear whether a truncated E1 protein could function as a replicative helicase for viral replication, it would still retain binding sites for potential interactions with different host cell proteins. Furthermore, in this study, we found evidence in support of expression of full-length HPV-18 E1 mRNA in HeLa cells. To determine whether interactions between E1 and cellular proteins play an important role in cellular processes other than viral replication, genome-wide expression profiles of HPV-18 positive HeLa cells were compared before and after the siRNA knockdown of E1 expression. Differential expression and gene set enrichment analysis uncovered four functionally related sets of genes implicated in host defence mechanisms against viral infection. These included the toll-like receptor, interferon and apoptosis pathways, along with the antiviral interferon-stimulated gene set. In addition, we found that the transcriptional coactivator E1A-binding protein p300 (EP300) was downregulated, which is interesting given that EP300 is thought to be required for the transcription of HPV-18 genes in HeLa cells. The observed changes in gene expression produced via the silencing of HPV-18 E1 expression in HeLa cells indicate that in addition to its well-known role in viral replication, the E1 protein may also play an important role in mitigating the host's ability to defend against viral infection.

  7. Occurrence in Mexico, 1998–2008, of Vibrio cholerae CTX+ El Tor carrying an additional truncated CTX prophage

    Science.gov (United States)

    Alam, Munirul; Rashed, Shah Manzur; Mannan, Shahnewaj Bin; Islam, Tarequl; Lizarraga-Partida, Marcial Leonardo; Delgado, Gabriela; Morales-Espinosa, Rosario; Mendez, Jose Luis; Navarro, Armando; Watanabe, Haruo; Ohnishi, Makoto; Hasan, Nur A.; Huq, Anwar; Sack, R. Bradley; Colwell, Rita R.; Cravioto, Alejandro

    2014-01-01

    The seventh cholera pandemic caused by Vibrio cholerae O1 El Tor (ET) has been superseded in Asia and Africa by altered ET possessing the cholera toxin (CTX) gene of classical (CL) biotype. The CL biotype of V. cholerae was isolated, along with prototypic and altered ET, during the 1991 cholera epidemic in Mexico and subsequently remained endemic until 1997. Microbiological, molecular, and phylogenetic analyses of clinical and environmental V. cholerae isolated in Mexico between 1998 and 2008 revealed important genetic events favoring predominance of ET over CL and altered ET. V. cholerae altered ET was predominant after 1991 but not after 2000. V. cholerae strains isolated between 2001 and 2003 and a majority isolated in 2004 lacked CTX prophage (Φ) genes encoding CTX subunits A and B and repeat sequence transcriptional regulators of ET and CL biotypes: i.e., CTXΦ−. Most CTXΦ− V. cholerae isolated in Mexico between 2001 and 2003 also lacked toxin coregulated pili tcpA whereas some carried either tcpAET or a variant tcpA with noticeable sequence dissimilarity from tcpACL. The tcpA variants were not detected in 2005 after CTXΦ+ ET became dominant. All clinical and environmental V. cholerae O1 strains isolated during 2005–2008 in Mexico were CTXΦ+ ET, carrying an additional truncated CTXΦ instead of RS1 satellite phage. Despite V. cholerae CTXΦ− ET exhibiting heterogeneity in pulsed-field gel electrophoresis patterns, CTXΦ+ ET isolated during 2004–2008 displayed homogeneity and clonal relationship with V. cholerae ET N16961 and V. cholerae ET isolated in Peru. PMID:24958870

  8. Effects of truncation of the peptide chain on the secondary structure and bioactivities of palmitoylated anoplin.

    Science.gov (United States)

    Salas, Remmer L; Garcia, Jan Kathryne D L; Miranda, Ana Carmela R; Rivera, Windell L; Nellas, Ricky B; Sabido, Portia Mahal G

    2018-06-01

    Anoplin (GLLKRIKTLL-NH 2 ) is of current interest due to its short sequence and specificity towards bacteria. Recent studies on anoplin have shown that truncation and acylation compromises its antimicrobial activity and specificity, respectively. In this study, truncated analogues (pal-ano-9 to pal-ano-5) of palmitoylated anoplin (pal-anoplin) were synthesized to determine the effects of C-truncation on its bioactivities. Moreover, secondary structure of each analogue using circular dichroism (CD) spectroscopy was determined to correlate with bioactivities. Interestingly, pal-anoplin, pal-ano-9 and pal-ano-6 were helical in water, unlike anoplin. In contrast, pal-ano-8, pal-ano-7 and pal-ano-5, with polar amino acid residues at the C-terminus, were random coil in water. Nevertheless, all the peptides folded into helical structures in 30% trifluoroethanol/water (TFE/H 2 O) except for the shortest analogue pal-ano-5. Hydrophobicity played a significant role in the enhancement of activity against bacteria E. coli and S. aureus as all lipopeptides including the random coil pal-ano-5 were more active than the parent anoplin. Meanwhile, the greatest improvement in activity against the fungus C. albicans was observed for pal-anoplin analogues (pal-ano-9 and pal-ano-6) that were helical in water. Although, hydrophobicity is a major factor in the secondary structure and antimicrobial activity, it appears that the nature of amino acids at the C-terminus also influence folding of lipopeptides in water and its antifungal activity. Moreover, the hemolytic activity of the analogues was found to correlate with hydrophobicity, except for the least hemolytic, pal-ano-5. Since most of the analogues are more potent and shorter than anoplin, they are promising drug candidates for further development. Copyright © 2018. Published by Elsevier Inc.

  9. Truncation of the many body hierarchy and relaxation times in the McKean model

    International Nuclear Information System (INIS)

    Schmitt, K.J.

    1987-01-01

    In the McKean model the BBGKY-hierarchy is equivalent to a simple hierarchy of coupled equations for the p-particle correlation functions. Truncation effects and the convergence of the one-particle distribution towards its exact shape have been studied. In the long time limit the equations can be solved in a closed form. It turns out that the p-particle correlation decays p-times faster than the non-equilibrium one-particle distribution

  10. TRUNCATION OF THE MANY BODY HIERARCHY AND RELAXATION TIMES IN THE McKEAN MODEL

    OpenAIRE

    Schmitt , K.-J.

    1987-01-01

    In the McKean model the BBGKY-hierarchy is equivalent to a simple hierarchy of coupled equations for the p-particle correlation functions. Truncation effects and the convergence of the one-particle distribution towards its exact shape have been studied. In the long time limit the equations can be solved in a closed form. It turns out that the p-particle correlation decays p-times faster than the non-equilibrium one-particle distribution.

  11. Pair truncation for rotational nuclei: j=17/2 model

    International Nuclear Information System (INIS)

    Halse, P.; Jaqua, L.; Barrett, B.R.

    1989-01-01

    The suitability of the pair condensate approach for rotational states is studied in a single j=17/2 shell of identical nucleons interacting through a quadrupole-quadrupole Hamiltonian. The ground band and a K=2 excited band are both studied in detail. A direct comparison of the exact states with those constituting the SD and SDG subspaces is used to identify the important degrees of freedom for these levels. The range of pairs necessary for a good description is found to be highly state dependent; S and D pairs are the major constituents of the low-spin ground-band levels, while G pairs are needed for those in the γ band. Energy spectra are obtained for each truncated subspace. SDG pairs allow accurate reproduction of the binding energy and K=2 excitation energy, but still give a moment of inertia which is about 30% too small even for the lowest levels

  12. N-terminal truncation enables crystallization of the receptor-binding domain of the FedF bacterial adhesin

    Energy Technology Data Exchange (ETDEWEB)

    De Kerpel, Maia; Van Molle, Inge [Department of Ultrastructure, Vrije Universiteit Brussel (VUB), Flanders Interuniversity Institute for Biotechnology (VIB), Pleinlaan 2, 1050 Brussels (Belgium); Brys, Lea [Department of Cellular and Molecular Immunology, Vrije Universiteit Brussel (VUB), Flanders Interuniversity Institute for Biotechnology (VIB), Pleinlaan 2, 1050 Brussels (Belgium); Wyns, Lode; De Greve, Henri; Bouckaert, Julie, E-mail: bouckaej@vub.ac.be [Department of Ultrastructure, Vrije Universiteit Brussel (VUB), Flanders Interuniversity Institute for Biotechnology (VIB), Pleinlaan 2, 1050 Brussels (Belgium)

    2006-12-01

    The N-terminal receptor-binding domain of the FedF adhesin from enterotoxigenic E. coli has been crystallized. This required the deletion of its first 14 residues, which are also cleaved off naturally. FedF is the two-domain tip adhesin of F18 fimbriae from enterotoxigenic Escherichia coli. Bacterial adherence, mediated by the N-terminal receptor-binding domain of FedF to carbohydrate receptors on intestinal microvilli, causes diarrhoea and oedema disease in newly weaned piglets and induces the secretion of Shiga toxins. A truncate containing only the receptor-binding domain of FedF was found to be further cleaved at its N-terminus. Reconstruction of this N-terminal truncate rendered FedF amenable to crystallization, resulting in crystals with space group P2{sub 1}2{sub 1}2{sub 1} and unit-cell parameters a = 36.20, b = 74.64, c = 99.03 Å that diffracted to beyond 2 Å resolution. The binding specificity of FedF was screened for on a glycan array, exposing 264 glycoconjugates, to identify specific receptors for cocrystallization with FedF.

  13. Consistent Kaluza-Klein truncations via exceptional field theory

    Energy Technology Data Exchange (ETDEWEB)

    Hohm, Olaf [Center for Theoretical Physics, Massachusetts Institute of Technology,Cambridge, MA 02139 (United States); Samtleben, Henning [Université de Lyon, Laboratoire de Physique, UMR 5672, CNRS,École Normale Supérieure de Lyon, 46, allée d’Italie, F-69364 Lyon cedex 07 (France)

    2015-01-26

    We present the generalized Scherk-Schwarz reduction ansatz for the full supersymmetric exceptional field theory in terms of group valued twist matrices subject to consistency equations. With this ansatz the field equations precisely reduce to those of lower-dimensional gauged supergravity parametrized by an embedding tensor. We explicitly construct a family of twist matrices as solutions of the consistency equations. They induce gauged supergravities with gauge groups SO(p,q) and CSO(p,q,r). Geometrically, they describe compactifications on internal spaces given by spheres and (warped) hyperboloides H{sup p,q}, thus extending the applicability of generalized Scherk-Schwarz reductions beyond homogeneous spaces. Together with the dictionary that relates exceptional field theory to D=11 and IIB supergravity, respectively, the construction defines an entire new family of consistent truncations of the original theories. These include not only compactifications on spheres of different dimensions (such as AdS{sub 5}×S{sup 5}), but also various hyperboloid compactifications giving rise to a higher-dimensional embedding of supergravities with non-compact and non-semisimple gauge groups.

  14. A numerical method for multigroup slab-geometry discrete ordinates problems with no spatial truncation error

    International Nuclear Information System (INIS)

    Barros, R.C. de; Larsen, E.W.

    1991-01-01

    A generalization of the one-group Spectral Green's Function (SGF) method is developed for multigroup, slab-geometry discrete ordinates (S N ) problems. The multigroup SGF method is free from spatial truncation errors; it generated numerical values for the cell-edge and cell-average angular fluxes that agree with the analytic solution of the multigroup S N equations. Numerical results are given to illustrate the method's accuracy

  15. Design and Synthesis of a Series of Truncated Neplanocin Fleximers

    Directory of Open Access Journals (Sweden)

    Sarah C. Zimmermann

    2014-12-01

    Full Text Available In an effort to study the effects of flexibility on enzyme recognition and activity, we have developed several different series of flexible nucleoside analogues in which the purine base is split into its respective imidazole and pyrimidine components. The focus of this particular study was to synthesize the truncated neplanocin A fleximers to investigate their potential anti-protozoan activities by inhibition of S-adenosylhomocysteine hydrolase (SAHase. The three fleximers tested displayed poor anti-trypanocidal activities, with EC50 values around 200 μM. Further studies of the corresponding ribose fleximers, most closely related to the natural nucleoside substrates, revealed low affinity for the known T. brucei nucleoside transporters P1 and P2, which may be the reason for the lack of trypanocidal activity observed.

  16. The robustness of truncated Airy beam in PT Gaussian potentials media

    Science.gov (United States)

    Wang, Xianni; Fu, Xiquan; Huang, Xianwei; Yang, Yijun; Bai, Yanfeng

    2018-03-01

    The robustness of truncated Airy beam in parity-time (PT) symmetric Gaussian potentials media is numerically investigated. A high-peak power beam sheds from the Airy beam due to the media modulation while the Airy wavefront still retain its self-bending and non-diffraction characteristics under the influence of modulation parameters. Increasing the modulation factor results in the smaller value of maximum power of the center beam, and the opposite trend occurs with the increment of the modulation depth. However, the parabolic trajectory of the Airy wavefront does not be influenced. By utilizing the unique features, the Airy beam can be used as a long distance transmission source under the PT symmetric Gaussian potentials medium.

  17. Pulse column hydrodynamics for liquid-liquid extraction with truncated-disc packing

    International Nuclear Information System (INIS)

    Bracou, H.; Hanssens, A.

    1993-01-01

    The experimental installation is composed of a stainless steel truncated disc packing with 25% of axial transparency, 25 mm of distance between the plates and 50 mm of diameter (DT 25/25/50 stainless steel). The phase system used during these tests is the hydrogenated tetra-propylene (HTP dispersed phase) /water (continuous phase) in continuous aqueous operating ''FAC'' method. The aim of this work is to gather the whole requisite data to the modelization stage based on the extrapolation of a mathematical tool, type population evaluation with a double object to supply the basis information useful for the model, and to establish an experimental data base for the model validation. 9 refs., 4 figs

  18. Murine bone marrow Lin⁻Sca⁻1⁺CD45⁻ very small embryonic-like (VSEL cells are heterogeneous population lacking Oct-4A expression.

    Directory of Open Access Journals (Sweden)

    Krzysztof Szade

    Full Text Available Murine very small embryonic-like (VSEL cells, defined by the Lin(-Sca-1(+CD45(- phenotype and small size, were described as pluripotent cells and proposed to be the most primitive hematopoietic precursors in adult bone marrow. Although their isolation and potential application rely entirely on flow cytometry, the immunophenotype of VSELs has not been extensively characterized. Our aim was to analyze the possible heterogeneity of Lin(-Sca(+CD45(- population and investigate the extent to which VSELs characteristics may overlap with that of hematopoietic stem cells (HSCs or endothelial progenitor cells (EPCs. The study evidenced that murine Lin(-Sca-1(+CD45(- population was heterogeneous in terms of c-Kit and KDR expression. Accordingly, the c-Kit(+KDR(-, c-Kit(-KDR(+, and c-Kit(-KDR(- subpopulations could be distinguished, while c-Kit(+KDR(+ events were very rare. The c-Kit(+KDR(- subset contained almost solely small cells, meeting the size criterion of VSELs, in contrast to relatively bigger c-Kit(-KDR(+ cells. The c-Kit(-KDR(-FSC(low subset was highly enriched in Annexin V-positive, apoptotic cells, hence omitted from further analysis. Importantly, using qRT-PCR, we evidenced lack of Oct-4A and Oct-4B mRNA expression either in whole adult murine bone marrow or in the sorted of Lin(-Sca-1(+CD45(-FSC(low population, even by single-cell qRT-PCR. We also found that the Lin(-Sca-1(+CD45(-c-Kit(+ subset did not exhibit hematopoietic potential in a single cell-derived colony in vitro assay, although it comprised the Sca-1(+c-Kit(+Lin(- (SKL CD34(-CD45(-CD105(+ cells, expressing particular HSC markers. Co-culture of Lin(-Sca-1(+CD45(-FSC(low with OP9 cells did not induce hematopoietic potential. Further investigation revealed that SKL CD45(-CD105(+ subset consisted of early apoptotic cells with fragmented chromatin, and could be contaminated with nuclei expelled from erythroblasts. Concluding, murine bone marrow Lin(-Sca-1(+CD45(-FSC(low cells are

  19. An improved method for purification of recombinant truncated heme oxygenase-1 by expanded bed adsorption and gel filtration.

    Science.gov (United States)

    Hu, Hong-Bo; Wang, Wei; Han, Ling; Zhou, Wen-Pu; Zhang, Xue-Hong

    2007-03-01

    Recombinant truncated human heme oxygenase-1 (hHO-1) expressed in Escherichia coli was efficiently separated and purified from feedstock by DEAE-ion exchange expanded bed adsorption. Protocol optimization of hHO-1 on DEAE adsorbent resulted in adsorption in 0 M NaCl and elution in 150 mM NaCl at a pH of 8.5. The active enzyme fractions separated from the expanded bed column were further purified by a Superdex 75 gel filtration step. The specific hHO-1 activity increased from 0.82 +/- 0.05 to 24.8 +/- 1.8 U/mg during the whole purification steps. The recovery and purification factor of truncated hHO-1 of the whole purification were 72.7 +/- 4.7 and 30.2 +/- 2.3%, respectively. This purification process can decrease the demand on the preparation of feedstock and simplify the purification process.

  20. The comprehensive electrophysiological study of curcuminoids on delayed-rectifier K+ currents in insulin-secreting cells.

    Science.gov (United States)

    Kuo, Ping-Chung; Yang, Chia-Jung; Lee, Yu-Chi; Chen, Pei-Chun; Liu, Yen-Chin; Wu, Sheng-Nan

    2018-01-15

    Curcumin (CUR) has been demonstrated to induce insulin release from pancreatic β-cells; however, how curcuminoids (including demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC)) exert any possible effects on membrane ion currents inherently in insulin-secreting cells remains largely unclear. The effects of CUR and other structurally similar curcuminoids on ion currents in rat insulin-secreting (INS-1) insulinoma cells were therefore investigated in this study. The effects of these compounds on ionic currents and membrane potential were studied by patch-clamp technique. CUR suppressed the amplitude of delayed-rectifier K + current (I K(DR) ) in a time-, state- and concentration-dependent manner in these cells and the inhibition was not reversed by diazoxide, nicorandil or chlorotoxin. The value of dissociation constant for CUR-induced suppression of I K(DR) in INS-1 cells was 1.26μM. Despite the inability of CUR to alter the activation rate of I K(DR) , it accelerated current inactivation elicited by membrane depolarization. Increasing CUR concentrations shifted the inactivation curve of I K(DR) to hyperpolarized potential and slowed the recovery of I K(DR) inactivation. CUR, DMC, and BDMC all exerted depressant actions on I K(DR) amplitude to a similar magnitude, although DMC and BDMC did not increase current inactivation clearly. CUR slightly suppressed the peak amplitude of voltage-gated Na + current. CUR, DMC and BDMC depolarized the resting potential and increased firing frequency of action potentials. The CUR-mediated decrease of I K(DR) and the increase of current inactivation also occurred in βTC-6 INS-1 cells. Taken these results together, these effects may be one of the possible mechanisms contributing their insulin-releasing effect. Copyright © 2017 Elsevier B.V. All rights reserved.