Cloning and characterization of cDNAs encoding the complete sequence of decay-accelerating factor of human complement

International Nuclear Information System (INIS)

Medof, M.E.; Lublin, D.M.; Holers, V.M.; Ayers, D.J.; Getty, R.R.; Leykam, J.F.; Atkinson, J.P.; Tykocinski, M.L.

1987-01-01

cDNAs encoding the complement decay-accelerating factor (DAF) were isolated from HeLa and differentiated HL-60 λgt cDNA libraries by screening with a codon preference oligonucleotide corresponding to DAF NH 2 -terminal amino acids 3-14. The composite cDNA sequence showed a 347-amino acid protein preceded by an NH 2 -terminal leader peptide sequence. The translated sequence beginning at the DAF NH 2 terminus encodes four contiguous ≅ 61-amino acid long repetitive units of internal homology. The repetitive regions contain four conserved cysteines, one proline, one glycine, one glycine/alanine, four leucines/isoleucines/valines, one serine, three tyrosines/phenylalanines, and on tryptophan and show striking homology to similar regions previously identified in factor B, C2, C4 binding protein, factor H, C1r, factor XIII, interleukin 2 receptor, and serum β 2 -glycoprotein I. The consensus repeats are attached to a 70-amino acid long segment rich in serine and threonine (potential O-glycosylation sites), which is in turn followed by a stretch of hydrophobic amino acids. RNA blot analysis of HeLa and HL-60 RNA revealed three DAF mRNA species of 3.1, 2.7, and 2.0 kilobases. The results indicate that portions of the DAF gene may have evolved from a DNA element common to the above proteins, that DAF cDNA predicts a COOH-terminal anchoring polypeptide, and that distinct species of DAF message are elaborated in cells

Porcine Knock-in Fibroblasts Expressing hDAF on α-1,3-Galactosyltransferase (GGTA1) Gene Locus.

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Kim, Ji Woo; Kim, Hye-Min; Lee, Sang Mi; Kang, Man-Jong

2012-10-01

The Galactose-α1,3-galactose (α1,3Gal) epitope is responsible for hyperacute rejection in pig-to-human xenotransplantation. Human decay-accelerating factor (hDAF) is a cell surface regulatory protein that serves as a complement inhibitor to protect self cells from complement attack. The generation of α1,3-galactosyltransferase (GGTA1) knock-out pigs expressing DAF is a necessary step for their use as organ donors for humans. In this study, we established GGTA1 knock-out cell lines expressing DAF from pig ear fibroblasts for somatic cell nuclear transfer. hDAF expression was detected in hDAF knock-in heterozygous cells, but not in normal pig cells. Expression of the GGTA1 gene was lower in the knock-in heterozygous cell line compared to the normal pig cell. Knock-in heterozygous cells afforded more effective protection against cytotoxicity with human serum than with GGTA1 knock-out heterozygous and control cells. These cell lines may be used in the production of GGTA1 knock-out and DAF expression pigs for xenotransplantation.

CAMKII and calcineurin regulate the lifespan of Caenorhabditis elegans through the FOXO transcription factor DAF-16.

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Tao, Li; Xie, Qi; Ding, Yue-He; Li, Shang-Tong; Peng, Shengyi; Zhang, Yan-Ping; Tan, Dan; Yuan, Zengqiang; Dong, Meng-Qiu

2013-06-25

The insulin-like signaling pathway maintains a relatively short wild-type lifespan in Caenorhabditis elegans by phosphorylating and inactivating DAF-16, the ortholog of the FOXO transcription factors of mammalian cells. DAF-16 is phosphorylated by the AKT kinases, preventing its nuclear translocation. Calcineurin (PP2B phosphatase) also limits the lifespan of C. elegans, but the mechanism through which it does so is unknown. Herein, we show that TAX-6•CNB-1 and UNC-43, the C. elegans Calcineurin and Ca(2+)/calmodulin-dependent kinase type II (CAMKII) orthologs, respectively, also regulate lifespan through DAF-16. Moreover, UNC-43 regulates DAF-16 in response to various stress conditions, including starvation, heat or oxidative stress, and cooperatively contributes to lifespan regulation by insulin signaling. However, unlike insulin signaling, UNC-43 phosphorylates and activates DAF-16, thus promoting its nuclear localization. The phosphorylation of DAF-16 at S286 by UNC-43 is removed by TAX-6•CNB-1, leading to DAF-16 inactivation. Mammalian FOXO3 is also regulated by CAMKIIA and Calcineurin. DOI:http://dx.doi.org/10.7554/eLife.00518.001.

An Expanded Role for the RFX Transcription Factor DAF-19, with Dual Functions in Ciliated and Nonciliated Neurons.

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De Stasio, Elizabeth A; Mueller, Katherine P; Bauer, Rosemary J; Hurlburt, Alexander J; Bice, Sophie A; Scholtz, Sophie L; Phirke, Prasad; Sugiaman-Trapman, Debora; Stinson, Loraina A; Olson, Haili B; Vogel, Savannah L; Ek-Vazquez, Zabdiel; Esemen, Yagmur; Korzynski, Jessica; Wolfe, Kelsey; Arbuckle, Bonnie N; Zhang, He; Lombard-Knapp, Gaelen; Piasecki, Brian P; Swoboda, Peter

2018-03-01

Regulatory Factor X (RFX) transcription factors (TFs) are best known for activating genes required for ciliogenesis in both vertebrates and invertebrates. In humans, eight RFX TFs have a variety of tissue-specific functions, while in the worm Caenorhabditis elegans , the sole RFX gene, daf-19 , encodes a set of nested isoforms. Null alleles of daf-19 confer pleiotropic effects including altered development with a dauer constitutive phenotype, complete absence of cilia and ciliary proteins, and defects in synaptic protein maintenance. We sought to identify RFX/ daf-19 target genes associated with neuronal functions other than ciliogenesis using comparative transcriptome analyses at different life stages of the worm. Subsequent characterization of gene expression patterns revealed one set of genes activated in the presence of DAF-19 in ciliated sensory neurons, whose activation requires the daf-19c isoform, also required for ciliogenesis. A second set of genes is downregulated in the presence of DAF-19, primarily in nonsensory neurons. The human orthologs of some of these neuronal genes are associated with human diseases. We report the novel finding that daf-19a is directly or indirectly responsible for downregulation of these neuronal genes in C. elegans by characterizing a new mutation affecting the daf-19a isoform ( tm5562 ) and not associated with ciliogenesis, but which confers synaptic and behavioral defects. Thus, we have identified a new regulatory role for RFX TFs in the nervous system. The new daf-19 candidate target genes we have identified by transcriptomics will serve to uncover the molecular underpinnings of the pleiotropic effects that daf-19 exerts on nervous system function. Copyright © 2018 by the Genetics Society of America.

Cooperation of decay-accelerating factor and membrane cofactor protein in regulating survival of human cervical cancer cells

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Gao, Ling-Juan; Guo, Shu-Yu; Cai, You-Qun; Gu, Ping-Qing; Su, Ya-Juan; Gong, Hui; Liu, Yun; Chen, Chen

2009-01-01

Decay-accelerating factor (DAF) and membrane cofactor protein (MCP) are the key molecules involved in cell protection against autologus complement, which restricts the action of complement at critical stages of the cascade reaction. The cooperative effect of DAF and MCP on the survival of human cervical cancer cell (ME180) has not been demonstrated. In this study we applied, for the first time, short hairpin RNA (shRNA) to knock down the expression of the DAF and MCP with the aim of exploiting complement more effectively for tumor cell damage. Meanwhile, we investigated the cooperative effects of DAF and MCP on the viability and migration, moreover the proliferation of ME180 cell. The results showed that shRNA inhibition of DAF and MCP expression enhanced complement-dependent cytolysis (CDC) up to 39% for MCP and up to 36% for DAF, and the combined inhibition of both regulators yielded further additive effects in ME180 cells. Thus, the activities of DAF and MCP, when present together, are greater than the sum of the two protein individually. These data indicated that combined DAF and MCP shRNA described in this study may offer an additional alternative to improve the efficacy of antibody-and complement-based cancer immunotherapy

Transcriptional regulation of Caenorhabditis elegans FOXO/DAF-16 modulates lifespan.

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Bansal, Ankita; Kwon, Eun-Soo; Conte, Darryl; Liu, Haibo; Gilchrist, Michael J; MacNeil, Lesley T; Tissenbaum, Heidi A

2014-01-01

Insulin/IGF-1 signaling plays a central role in longevity across phylogeny. In C. elegans, the forkhead box O (FOXO) transcription factor, DAF-16, is the primary target of insulin/IGF-1 signaling, and multiple isoforms of DAF-16 (a, b, and d/f) modulate lifespan, metabolism, dauer formation, and stress resistance. Thus far, across phylogeny modulation of mammalian FOXOs and DAF-16 have focused on post-translational regulation with little focus on transcriptional regulation. In C. elegans, we have previously shown that DAF-16d/f cooperates with DAF-16a to promote longevity. In this study, we generated transgenic strains expressing near-endogenous levels of either daf-16a or daf-16d/f, and examined temporal expression of the isoforms to further define how these isoforms contribute to lifespan regulation. Here, we show that DAF-16a is sensitive both to changes in gene dosage and to alterations in the level of insulin/IGF-1 signaling. Interestingly, we find that as worms age, the intestinal expression of daf-16d/f but not daf-16a is dramatically upregulated at the level of transcription. Preventing this transcriptional upregulation shortens lifespan, indicating that transcriptional regulation of daf-16d/f promotes longevity. In an RNAi screen of transcriptional regulators, we identify elt-2 (GATA transcription factor) and swsn-1 (core subunit of SWI/SNF complex) as key modulators of daf-16d/f gene expression. ELT-2 and another GATA factor, ELT-4, promote longevity via both DAF-16a and DAF-16d/f while the components of SWI/SNF complex promote longevity specifically via DAF-16d/f. Our findings indicate that transcriptional control of C. elegans FOXO/daf-16 is an essential regulatory event. Considering the conservation of FOXO across species, our findings identify a new layer of FOXO regulation as a potential determinant of mammalian longevity and age-related diseases such as cancer and diabetes.

CD97-decay-accelerating factor interaction is not involved in leukocyte adhesion to endothelial cells

NARCIS (Netherlands)

Boulday, Gwénola; Hamann, Jörg; Soulillou, Jean-Paul; Charreau, Béatrice

2002-01-01

Background. Effective improvement in xenograft survival is achieved using transplants from transgenic pigs expressing human complement (C) regulatory proteins, including decay-accelerating factor (DAF), CD59, and CD46 on endothelial cells (ECs). The aim of this study was to investigate whether human

A functional SNP in the regulatory region of the decay-accelerating factor gene associates with extraocular muscle pareses in myasthenia gravis

KAUST Repository

Heckmann, J M

2009-08-13

Complement activation in myasthenia gravis (MG) may damage muscle endplate and complement regulatory proteins such as decay-accelerating factor (DAF) or CD55 may be protective. We hypothesize that the increased prevalence of severe extraocular muscle (EOM) dysfunction among African MG subjects reported earlier may result from altered DAF expression. To test this hypothesis, we screened the DAF gene sequences relevant to the classical complement pathway and found an association between myasthenics with EOM paresis and the DAF regulatory region c.-198CG SNP (odds ratio8.6; P0.0003). This single nucleotide polymorphism (SNP) results in a twofold activation of a DAF 5?-flanking region luciferase reporter transfected into three different cell lines. Direct matching of the surrounding SNP sequence within the DAF regulatory region with the known transcription factor-binding sites suggests a loss of an Sp1-binding site. This was supported by the observation that the c.-198CG SNP did not show the normal lipopolysaccharide-induced DAF transcriptional upregulation in lymphoblasts from four patients. Our findings suggest that at critical periods during autoimmune MG, this SNP may result in inadequate DAF upregulation with consequent complement-mediated EOM damage. Susceptible individuals may benefit from anti-complement therapy in addition to immunosuppression. © 2010 Macmillan Publishers Limited. All rights reserved.

Immunohistochemical Expression and Prognostic Significance of CD97 and its Ligand DAF in Human Cervical Squamous Cell Carcinoma.

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He, Ying; Wang, Wei; Xu, Lian; Li, Li; Liu, Juan; Feng, Min; Bu, Hong

2015-09-01

Accumulating evidences had demonstrated that the CD97, a member of the epidermal growth factor 7-transmembrane family, and its cellular ligand decay accelerating factor (DAF) both play important roles in tumor dedifferentiation, migration, invasiveness, and metastasis. However, the roles of CD97 and DAF in human cervical squamous cell carcinoma (CSCC) have not been investigated. The purpose of this study was to observe the expression profile of CD97 and DAF in CSCC and evaluate their clinical significance. Immunohistochemistry was used to investigate the expression of CD97 and DAF proteins in 97 patients with CSCC and 53 patients with cervical intraepithelial neoplasia, a precursor lesion of CSCC. CD97 and DAF were absent or only weakly expressed in the normal epithelium of the cervix but were present in 83.5% (81/97) and 90.7% (88/97) of CSCC samples, respectively. Overexpression of CD97 was significantly associated with a high International Federation of Gynecology and Obstetrics stage (P=0.010) and lymph node metastasis (P=0.026). The majority of CSCCs, irrespective of staging/grading classification, displayed strong DAF immunostaining. Kaplan-Meier survival analysis revealed that overexpression of CD97 was associated with a worse prognosis. Multivariate analyses showed that the International Federation of Gynecology and Obstetrics stage (P=0.000), lymph node metastasis (P=0.004), and CD97 expression (P=0.040) were independent risk factors for overall survival. The present study suggested that the expressions of CD97 and DAF were both upregulated in CSCC. The expression level of CD97 in CSCC was associated with the severity of the tumor. Furthermore, CD97 might be an independent poor prognostic factor for CSCC patients.

Strongyloides stercoralis daf-2 encodes a divergent ortholog of Caenorhabditis elegans DAF-2.

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Massey, Holman C; Ranjit, Najju; Stoltzfus, Jonathan D; Lok, James B

2013-06-01

We hypothesise that developmental arrest in infectious larvae of parasitic nematodes is regulated by signalling pathways homologous to Caenorhabditis elegans DAF (dauer formation) pathways. Alignment of Strongyloides stercoralis (Ss) DAF-2 with DAF-2 of C. elegans and homologs of other species shows that most structural motifs in these insulin-like receptors are conserved. However, the catalytic domain of Ss-DAF-2 contains two substitutions (Q1242 and Q1256), that would result in constitutive dauer formation in C. elegans or diabetes in vertebrate animals. Ss-daf-2 also shows two alternately spliced isoforms, the constitutively expressed Ss-daf-2a, and Ss-daf-2b, which is only expressed in stages leading to parasitism. Copyright © 2013 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

dbl-1/TGF-β and daf-12/NHR Signaling Mediate Cell-Nonautonomous Effects of daf-16/FOXO on Starvation-Induced Developmental Arrest.

Directory of Open Access Journals (Sweden)

Rebecca E W Kaplan

2015-12-01

Full Text Available Nutrient availability has profound influence on development. In the nematode C. elegans, nutrient availability governs post-embryonic development. L1-stage larvae remain in a state of developmental arrest after hatching until they feed. This "L1 arrest" (or "L1 diapause" is associated with increased stress resistance, supporting starvation survival. Loss of the transcription factor daf-16/FOXO, an effector of insulin/IGF signaling, results in arrest-defective and starvation-sensitive phenotypes. We show that daf-16/FOXO regulates L1 arrest cell-nonautonomously, suggesting that insulin/IGF signaling regulates at least one additional signaling pathway. We used mRNA-seq to identify candidate signaling molecules affected by daf-16/FOXO during L1 arrest. dbl-1/TGF-β, a ligand for the Sma/Mab pathway, daf-12/NHR and daf-36/oxygenase, an upstream component of the daf-12 steroid hormone signaling pathway, were up-regulated during L1 arrest in a daf-16/FOXO mutant. Using genetic epistasis analysis, we show that dbl-1/TGF-β and daf-12/NHR steroid hormone signaling pathways are required for the daf-16/FOXO arrest-defective phenotype, suggesting that daf-16/FOXO represses dbl-1/TGF-β, daf-12/NHR and daf-36/oxygenase. The dbl-1/TGF-β and daf-12/NHR pathways have not previously been shown to affect L1 development, but we found that disruption of these pathways delayed L1 development in fed larvae, consistent with these pathways promoting development in starved daf-16/FOXO mutants. Though the dbl-1/TGF-β and daf-12/NHR pathways are epistatic to daf-16/FOXO for the arrest-defective phenotype, disruption of these pathways does not suppress starvation sensitivity of daf-16/FOXO mutants. This observation uncouples starvation survival from developmental arrest, indicating that DAF-16/FOXO targets distinct effectors for each phenotype and revealing that inappropriate development during starvation does not cause the early demise of daf-16/FOXO mutants. Overall

dbl-1/TGF-β and daf-12/NHR Signaling Mediate Cell-Nonautonomous Effects of daf-16/FOXO on Starvation-Induced Developmental Arrest.

Science.gov (United States)

Kaplan, Rebecca E W; Chen, Yutao; Moore, Brad T; Jordan, James M; Maxwell, Colin S; Schindler, Adam J; Baugh, L Ryan

2015-12-01

Nutrient availability has profound influence on development. In the nematode C. elegans, nutrient availability governs post-embryonic development. L1-stage larvae remain in a state of developmental arrest after hatching until they feed. This "L1 arrest" (or "L1 diapause") is associated with increased stress resistance, supporting starvation survival. Loss of the transcription factor daf-16/FOXO, an effector of insulin/IGF signaling, results in arrest-defective and starvation-sensitive phenotypes. We show that daf-16/FOXO regulates L1 arrest cell-nonautonomously, suggesting that insulin/IGF signaling regulates at least one additional signaling pathway. We used mRNA-seq to identify candidate signaling molecules affected by daf-16/FOXO during L1 arrest. dbl-1/TGF-β, a ligand for the Sma/Mab pathway, daf-12/NHR and daf-36/oxygenase, an upstream component of the daf-12 steroid hormone signaling pathway, were up-regulated during L1 arrest in a daf-16/FOXO mutant. Using genetic epistasis analysis, we show that dbl-1/TGF-β and daf-12/NHR steroid hormone signaling pathways are required for the daf-16/FOXO arrest-defective phenotype, suggesting that daf-16/FOXO represses dbl-1/TGF-β, daf-12/NHR and daf-36/oxygenase. The dbl-1/TGF-β and daf-12/NHR pathways have not previously been shown to affect L1 development, but we found that disruption of these pathways delayed L1 development in fed larvae, consistent with these pathways promoting development in starved daf-16/FOXO mutants. Though the dbl-1/TGF-β and daf-12/NHR pathways are epistatic to daf-16/FOXO for the arrest-defective phenotype, disruption of these pathways does not suppress starvation sensitivity of daf-16/FOXO mutants. This observation uncouples starvation survival from developmental arrest, indicating that DAF-16/FOXO targets distinct effectors for each phenotype and revealing that inappropriate development during starvation does not cause the early demise of daf-16/FOXO mutants. Overall, this study shows

Selective expression of a splice variant of decay-accelerating factor in c-erbB-2-positive mammary carcinoma cells showing increased transendothelial invasiveness

International Nuclear Information System (INIS)

Brandt, Burkhard; Mikesch, Jan-Hendrik; Simon, Ronald; Roetger, Antje; Kemming, Dirk; Schier, Katrin; Sauter, Guido; Buerger, Horst

2005-01-01

By differential-display-PCR a subclone of the SK-BR-3 cell line with high in vitro transendothelial invasiveness was identified to express increased levels of a new alternative splice variant of decay-accelerating factor (DAF). DAF seems to play an important role in some malignant tumours since on the one hand the expression of complement inhibitors on the surface of tumour cells prevents the accumulation of complement factors and in consequence cell lysis. On the other hand, DAF has been identified as a ligand for the CD97 surface receptor which induces cell migration. Immunofluorescence procedures, Western blot analyses, and cDNA clone sequencing were employed to confirm the expression of DAF restricted to invasive tumour cells. Using a radioactive RNA-in situ hybridisation on freshly frozen tissue microarrays and RT-PCR on native tumour tissue, the expression of alternative spliced DAF mRNA was demonstrated in invasive breast cancer. Due to the fact that it could thereby not be detected in normal mammary tissues, it has to be confirmed in larger studies that the DAF splice variant might be a specific tumour marker for invasive breast cancer

A functional SNP in the regulatory region of the decay-accelerating factor gene associates with extraocular muscle pareses in myasthenia gravis

KAUST Repository

Heckmann, J M; Uwimpuhwe, H; Ballo, R; Kaur, M; Bajic, Vladimir B.; Prince, S

2009-01-01

Complement activation in myasthenia gravis (MG) may damage muscle endplate and complement regulatory proteins such as decay-accelerating factor (DAF) or CD55 may be protective. We hypothesize that the increased prevalence of severe extraocular

DAF-16: FOXO in the Context of C. elegans.

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Tissenbaum, Heidi A

2018-01-01

In Caenorhabditis elegans, there is a single FOXO transcription factor homolog, encoded by the gene, daf-16. As a central regulator for multiple signaling pathways, DAF-16 integrates these signals which results in modulation of several biological processes including longevity, development, fat storage, stress resistance, innate immunity, and reproduction. Using C. elegans allows for studies of FOXO in the context of the whole animal. Therefore, manipulating levels or the activity of daf-16 results in phenotypic changes. Genetic and molecular analysis revealed that similar to other systems, DAF-16 is the downstream target of the conserved insulin/IGF-1 signaling (IIS) pathway; a PI 3-kinase/AKT signaling cascade that ultimately controls the regulation of DAF-16 nuclear localization. In this chapter, I will focus on understanding how a single gene daf-16 can incorporate signals from multiple upstream pathways and in turn modulate different phenotypes as well as the study of FOXO in the context of a whole organism. © 2018 Elsevier Inc. All rights reserved.

Decay Accelerating Factor (CD55) Protects Neuronal Cells from Chemical Hypoxia-Induced Injury

Science.gov (United States)

2010-04-09

Pavlakovic G, Isom GE: Dopaminergic neurotoxicity of cyanide: neurochemical, histological and behavioral characterization. Toxicol Appl Pharmacol...provided the original work is properly cited. ResearchDecay accelerating factor (CD55) protects neuronal cells from chemical hypoxia-induced injury...deposition of C3a/C5a and membrane attack complex (MAC or C5b-9) production. The present study investigates the ability of DAF to protect primary cultured

Calycosin promotes lifespan in Caenorhabditis elegans through insulin signaling pathway via daf-16, age-1 and daf-2.

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Lu, Lulu; Zhao, Xuan; Zhang, Jianyong; Li, Miao; Qi, Yonghao; Zhou, Lijun

2017-07-01

The naturally occurring calycosin is a known antioxidant that prevents redox imbalance in organisms. However, calycosin's effect on lifespan and its physiological molecular mechanisms are not yet well understood. In this study, we demonstrated that calycosin could prolong the lifespan of Caenorhabditis elegans, and that such extension was associated with its antioxidant capability as well as its ability to enhance stress resistance and reduce ROS (reactive oxygen species) accumulation. To explore mechanisms of this longevity effect, we assessed the impact of calycosin on lifespans of insulin-signaling impaired worms: daf-2, age-1, and daf-16 mutants. We found that calycosin did not alter the lifespan of all three mutants, thereby suggesting that calycosin requires insulin signaling to promote lifespan extension. On the other hand, we observed that calycosin could enhance the nuclear translocation of the core transcription factor DAF-16/FoXO instead of the conserved stress-responsive transcription factor SKN-1/Nrf-2. This observation is consistent with the understanding that the nuclear localized DAF-16 up-regulates its downstream targets sod-3, ctl-1, and hsp-16.2. Lastly, it is also noteworthy that the longevity effect of calycosin is likely not associated with the calorie restriction mechanism. Collectively, our results strongly suggest that calycosin could function as an antioxidant to extend the lifespan of C. elegans by enhancing nucleus translocation of DAF-16 through the insulin-signaling pathway. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Sterol-derived hormone(s controls entry into diapause in Caenorhabditis elegans by consecutive activation of DAF-12 and DAF-16.

Directory of Open Access Journals (Sweden)

Vitali Matyash

2004-10-01

Full Text Available Upon starvation or overcrowding, Caenorhabditis elegans interrupts its reproductive cycle and forms a specialised larva called dauer (enduring. This process is regulated by TGF-beta and insulin-signalling pathways and is connected with the control of life span through the insulin pathway components DAF-2 and DAF-16. We found that replacing cholesterol with its methylated metabolite lophenol induced worms to form dauer larvae in the presence of food and low population density. Our data indicate that methylated sterols do not actively induce the dauer formation but rather that the reproductive growth requires a cholesterol-derived hormone that cannot be produced from methylated sterols. Using the effect of lophenol on growth, we have partially purified activity, named gamravali, which promotes the reproduction. In addition, the effect of lophenol allowed us to determine the role of sterols during dauer larva formation and longevity. In the absence of gamravali, the nuclear hormone receptor DAF-12 is activated and thereby initiates the dauer formation program. Active DAF-12 triggers in neurons the nuclear import of DAF-16, a forkhead domain transcription factor that contributes to dauer differentiation. This hormonal control of DAF-16 activation is, however, independent of insulin signalling and has no influence on life span.

FoxO/Daf-16 restored thrashing movement reduced by heat stress in Caenorhabditis elegans.

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Furuhashi, Tsubasa; Sakamoto, Kazuichi

2014-04-01

Many studies on thermotolerance have been done in Caenorhabditis elegans in order to extend survival under heat stress; Daf-16, a homolog of FoxO in C. elegans, was detected as the key factor in thermotolerance. However, the recovery process from heat stress damage has been seldom discussed. In this study, we analyzed the roles of FoxO/Daf-16 on the recovery from heat stress damage by monitoring thrashing movement. Heat shock reduced the movement, which was restored by culturing at 20°C. Thrashing movement was not restored in the daf-16 mutant, which suggests that Daf-16 is one of the essential factors in repairing the damage. Movement restoration was promoted in the daf-2 mutant, a homolog of insulin/IGF-1-like receptor, in a daf-16-dependent manner. In addition, heat stress decreased the expression of daf-28 and ins-7, agonists of Daf-2. Taken together, these results revealed that FoxO/Daf-16 removes heat stress damage and restores movement via inhibition of the insulin-like signaling pathway in C. elegans, suggesting that FoxO/Daf-16 plays a critical role in thermotolerance. Copyright © 2014 Elsevier Inc. All rights reserved.

RFX Transcription Factor DAF-19 Regulates 5-HT and Innate Immune Responses to Pathogenic Bacteria in Caenorhabditis elegans

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Choi, Sunju; Xu, Lu; Sze, Ji Ying

2013-01-01

In Caenorhabditis elegans the Toll-interleukin receptor domain adaptor protein TIR-1 via a conserved mitogen-activated protein kinase (MAPK) signaling cascade induces innate immunity and upregulates serotonin (5-HT) biosynthesis gene tph-1 in a pair of ADF chemosensory neurons in response to infection. Here, we identify transcription factors downstream of the TIR-1 signaling pathway. We show that common transcription factors control the innate immunity and 5-HT biosynthesis. We demonstrate that a cysteine to tyrosine substitution in an ARM motif of the HEAT/Arm repeat region of the TIR-1 protein confers TIR-1 hyperactivation, leading to constitutive tph-1 upregulation in the ADF neurons, increased expression of intestinal antimicrobial genes, and enhanced resistance to killing by the human opportunistic pathogen Pseudomonas aeruginosa PA14. A forward genetic screen for suppressors of the hyperactive TIR-1 led to the identification of DAF-19, an ortholog of regulatory factor X (RFX) transcription factors that are required for human adaptive immunity. We show that DAF-19 concerts with ATF-7, a member of the activating transcription factor (ATF)/cAMP response element-binding B (CREB) family of transcription factors, to regulate tph-1 and antimicrobial genes, reminiscent of RFX-CREB interaction in human immune cells. daf-19 mutants display heightened susceptibility to killing by PA14. Remarkably, whereas the TIR-1-MAPK-DAF-19/ATF-7 pathway in the intestinal immunity is regulated by DKF-2/protein kinase D, we found that the regulation of tph-1 expression is independent of DKF-2 but requires UNC-43/Ca2+/calmodulin-dependent protein kinase (CaMK) II. Our results suggest that pathogenic cues trigger a common core-signaling pathway via tissue-specific mechanisms and demonstrate a novel role for RFX factors in neuronal and innate immune responses to infection. PMID:23505381

Isoxanthohumol, a constituent of hop (Humulus lupulus L.), increases stress resistance in Caenorhabditis elegans dependent on the transcription factor DAF-16.

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Büchter, Christian; Havermann, Susannah; Koch, Karoline; Wätjen, Wim

2016-02-01

The flavanone isoxanthohumol (IX) has gained attention as antioxidative and chemopreventive agent, but the molecular mechanism of action remains unclear. We investigated effects of this secondary plant compound in vivo using the model organism Caenorhabditis elegans. Adult C. elegans nematodes were incubated with IX, and then, the stress resistance was analysed in the SYTOX assay; lifespan was monitored by touch-provoked movement method, the amount of reactive oxygen species (ROS) was measured in the DCF assay, and the nuclear localisation of the transcription factor DAF-16 was analysed by using a transgenic strain. By the use of a DAF-16 loss-of-function strain, we analysed whether the effects are dependent on DAF-16. IX increases the resistance of the nematode against thermal stress. Additionally, a reduction in ROS in vivo was caused by IX. Since the flavanone only has a marginal radical-scavenging capacity (TEAC assay), we suggest that IX mediates its antioxidative effects indirectly via activation of DAF-16 (homologue to mammalian FOXO proteins). The nuclear translocation of this transcription factor is increased by IX. In the DAF-16-mutated strain, the IX-mediated increase in stress resistance was completely abolished; furthermore, an increased formation of ROS and a reduced lifespan was mediated by IX. IX or a bacterial metabolite of IX causes antioxidative effects as well as an increased stress resistance in C. elegans via activation of DAF-16. The homologous pathway may have implications in the molecular mechanism of IX in mammals.

Longevity Genes Revealed by Integrative Analysis of Isoform-Specific daf-16/FoxO Mutants of Caenorhabditis elegans.

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Chen, Albert Tzong-Yang; Guo, Chunfang; Itani, Omar A; Budaitis, Breane G; Williams, Travis W; Hopkins, Christopher E; McEachin, Richard C; Pande, Manjusha; Grant, Ana R; Yoshina, Sawako; Mitani, Shohei; Hu, Patrick J

2015-10-01

FoxO transcription factors promote longevity across taxa. How they do so is poorly understood. In the nematode Caenorhabditis elegans, the A- and F-isoforms of the FoxO transcription factor DAF-16 extend life span in the context of reduced DAF-2 insulin-like growth factor receptor (IGFR) signaling. To elucidate the mechanistic basis for DAF-16/FoxO-dependent life span extension, we performed an integrative analysis of isoform-specific daf-16/FoxO mutants. In contrast to previous studies suggesting that DAF-16F plays a more prominent role in life span control than DAF-16A, isoform-specific daf-16/FoxO mutant phenotypes and whole transcriptome profiling revealed a predominant role for DAF-16A over DAF-16F in life span control, stress resistance, and target gene regulation. Integration of these datasets enabled the prioritization of a subset of 92 DAF-16/FoxO target genes for functional interrogation. Among 29 genes tested, two DAF-16A-specific target genes significantly influenced longevity. A loss-of-function mutation in the conserved gene gst-20, which is induced by DAF-16A, reduced life span extension in the context of daf-2/IGFR RNAi without influencing longevity in animals subjected to control RNAi. Therefore, gst-20 promotes DAF-16/FoxO-dependent longevity. Conversely, a loss-of-function mutation in srr-4, a gene encoding a seven-transmembrane-domain receptor family member that is repressed by DAF-16A, extended life span in control animals, indicating that DAF-16/FoxO may extend life span at least in part by reducing srr-4 expression. Our discovery of new longevity genes underscores the efficacy of our integrative strategy while providing a general framework for identifying specific downstream gene regulatory events that contribute substantially to transcription factor functions. As FoxO transcription factors have conserved functions in promoting longevity and may be dysregulated in aging-related diseases, these findings promise to illuminate fundamental

Transgenic C. elegans dauer larvae expressing hookworm phospho null DAF-16/FoxO exit dauer.

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Verena Gelmedin

Full Text Available Parasitic hookworms and the free-living model nematode Caenorhabtidis elegans share a developmental arrested stage, called the dauer stage in C. elegans and the infective third-stage larva (L3 in hookworms. One of the key transcription factors that regulate entrance to and exit from developmental arrest is the forkhead transcription factor DAF-16/FoxO. During the dauer stage, DAF-16 is activated and localized in the nucleus. DAF-16 is negatively regulated by phosphorylation by the upstream kinase AKT, which causes DAF-16 to localize out of the nucleus and the worm to exit from dauer. DAF-16 is conserved in hookworms, and hypothesized to control recovery from L3 arrest during infection. Lacking reverse genetic techniques for use in hookworms, we used C. elegans complementation assays to investigate the function of Ancylostoma caninum DAF-16 during entrance and exit from L3 developmental arrest. We performed dauer switching assays and observed the restoration of the dauer phenotype when Ac-DAF-16 was expressed in temperature-sensitive dauer defective C. elegans daf-2(e1370;daf-16(mu86 mutants. AKT phosphorylation site mutants of Ac-DAF-16 were also able to restore the dauer phenotype, but surprisingly allowed dauer exit when temperatures were lowered. We used fluorescence microscopy to localize DAF-16 during dauer and exit from dauer in C. elegans DAF-16 mutant worms expressing Ac-DAF-16, and found that Ac-DAF-16 exited the nucleus during dauer exit. Surprisingly, Ac-DAF-16 with mutated AKT phosphorylation sites also exited the nucleus during dauer exit. Our results suggest that another mechanism may be involved in the regulation DAF-16 nuclear localization during recovery from developmental arrest.

Daf-2, Daf-16 and Daf-23: Genetically Interacting Genes Controlling Dauer Formation in Caenorhabditis Elegans

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Gottlieb, S.; Ruvkun, G.

1994-01-01

Under conditions of high population density and low food, Caenorhabditis elegans forms an alternative third larval stage, called the dauer stage, which is resistant to desiccation and harsh environments. Genetic analysis of some dauer constitutive (Daf-c) and dauer defective (Daf-d) mutants has revealed a complex pathway that is likely to function in particular neurons and/or responding tissues. Here we analyze the genetic interactions between three genes which comprise a branch of the dauer ...

Analysis list: daf-16 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available daf-16 Adult + ce10 http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/target/daf-16.1....tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/target/daf-16.5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/target/daf...-16.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/colo/daf-16.Adult.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/colo/Adult.gml ...

Analysis list: daf-12 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available daf-12 Larvae + ce10 http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/target/daf-12....1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/target/daf-12.5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/target/daf...-12.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/colo/daf-12.Larvae.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/colo/Larvae.gml ...

Redox-dependent control of FOXO/DAF-16 by transportin-1.

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Putker, Marrit; Madl, Tobias; Vos, Harmjan R; de Ruiter, Hesther; Visscher, Marieke; van den Berg, Maaike C W; Kaplan, Mohammed; Korswagen, Hendrik C; Boelens, Rolf; Vermeulen, Michiel; Burgering, Boudewijn M T; Dansen, Tobias B

2013-02-21

Forkhead box O (FOXO; DAF-16 in worms) transcription factors, which are of vital importance in cell-cycle control, stress resistance, tumor suppression, and organismal lifespan, are largely regulated through nucleo-cytoplasmic shuttling. Insulin signaling keeps FOXO/DAF-16 cytoplasmic, and hence transcriptionally inactive. Conversely, as in loss of insulin signaling, reactive oxygen species (ROS) can activate FOXO/DAF-16 through nuclear accumulation. How ROS regulate the nuclear translocation of FOXO/DAF-16 is largely unknown. Cysteine oxidation can stabilize protein-protein interactions through the formation of disulfide-bridges when cells encounter ROS. Using a proteome-wide screen that identifies ROS-induced mixed disulfide-dependent complexes, we discovered several interaction partners of FOXO4, one of which is the nuclear import receptor transportin-1. We show that disulfide formation with transportin-1 is required for nuclear localization and the activation of FOXO4/DAF-16 induced by ROS, but not by the loss of insulin signaling. This molecular mechanism for nuclear shuttling is conserved in C. elegans and directly connects redox signaling to the longevity protein FOXO/DAF-16. Copyright © 2013 Elsevier Inc. All rights reserved.

Interaction of hookworm 14-3-3 with the forkhead transcription factor DAF-16 requires intact Akt phosphorylation sites

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Hawdon John M

2009-04-01

Full Text Available Abstract Background Third-stage infective larvae (L3 of hookworms are in an obligatory state of developmental arrest that ends upon entering the definitive host, where they receive a signal that re-activates development. Recovery from the developmentally arrested dauer stage of Caenorhabditis elegans is analogous to the resumption of development during hookworm infection. Insulin-like signaling (ILS mediates recovery from arrest in C. elegans and activation of hookworm dauer L3. In C. elegans, phosphorylation of the forkhead transcription factor DAF-16 in response to ILS creates binding cites for the 14-3-3 protein Ce-FTT-2, which translocates DAF-16 out of the nucleus, resulting in resumption of reproductive development. Results To determine if hookworm 14-3-3 proteins play a similar role in L3 activation, hookworm FTT-2 was identified and tested for its ability to interact with A. caninum DAF-16 in vitro. The Ac-FTT-2 amino acid sequence was 91% identical to the Ce-FTT-2, and was most closely related to FTT-2 from other nematodes. Ac-FTT-2 was expressed in HEK 293T cells, and was recognized by an antibody against human 14-3-3β isoform. Reciprocal co-immunoprecipitations using anti-epitope tag antibodies indicated that Ac-FTT-2 interacts with Ac-DAF-16 when co-expressed in serum-stimulated HEK 293T cells. This interaction requires intact Akt consensus phosphorylation sites at serine107 and threonine312, but not serine381. Ac-FTT-2 was undetectable by Western blot in excretory/secretory products from serum-stimulated (activated L3 or adult A. caninum. Conclusion The results indicate that Ac-FTT-2 interacts with DAF-16 in a phosphorylation-site dependent manner, and suggests that Ac-FTT-2 mediates activation of L3 by binding Ac-DAF-16 during hookworm infection.

Difference in Ulex europaeus agglutinin I-binding activity of decay-accelerating factor detected in the stools of patients with colorectal cancer and ulcerative colitis.

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Okazaki, Hiroaki; Mizuno, Motowo; Nasu, Junichirou; Makidono, Chiho; Hiraoka, Sakiko; Yamamoto, Kazuhide; Okada, Hiroyuki; Fujita, Teizo; Tsuji, Takao; Shiratori, Yasushi

2004-03-01

Expression of decay-accelerating factor (DAF, CD55), a complement-regulatory glycoprotein, is enhanced in colorectal-cancer (CC) cells and colonic epithelium in ulcerative colitis (UC), and stools from these patients contain increased amounts of DAF. Carbohydrate chains of glycoproteins are often altered during malignant transformation or inflammation. In this study, we investigated whether DAF molecules in patients with CC and those with UC differ with respect to oligosaccharide side chains. We analyzed DAF in stools and homogenates of colonic-tissue specimens obtained from patients with CC or UC using solid-phase enzyme-linked assay and Western blotting for reactivity with the lectins Ulex europaeus agglutinin I (UEA-I), wheat-germ agglutinin, peanut agglutinin, and concanavalin A. UEA-I bound to DAF in stools from patients with UC but not in that from the stools of CC patients, as demonstrated on the solid-phase enzyme-linked assay (P <.05, Mann-Whitney U test) and Western blotting. Binding of UEA-I was specifically inhibited by the addition of fucose. The difference in UEA-I reactivity with DAF was observed also in colonic-tissue homogenates from patients with UC and those with CC. DAF expressed in the mucosa and excreted into the stools of UC patients is different from that expressed in CC with regard to UEA-I reactivity. Future studies should be directed toward determining whether a qualitatively unique isoform of DAF is present, of which sugar chains are specific to CC in UC patients.

Structural and functional characterisation of FOXO/Acan-DAF-16 from the parasitic nematode Angiostrongylus cantonensis.

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Yan, Baolong; Sun, Weiwei; Yan, Lanzhu; Zhang, Liangliang; Zheng, Yuan; Zeng, Yuzhen; Huang, Huicong; Liang, Shaohui

2016-12-01

Fork head box transcription factors subfamily O (FoxO) is regarded to be significant in cell-cycle control, cell differentiation, ageing, stress response, apoptosis, tumour formation and DNA damage repair. In the free-living nematode Caenorhabditis elegans, the FoxO transcription factor is encoded by Ce-daf-16, which is negatively regulated by insulin-like signaling (IIS) and involved in promoting dauer formation through bringing about its hundreds of downstream genes expression. In nematode parasites, orthologues of daf-16 from several species have been identified, with functions in rescue of dauer phenotypes determined in a surrogate system C. elegans. In this study, we identified the FoxO encoding gene, Acan-daf-16, from the parasitic nematode Angiostrongylus cantonensis, and determined the genomic structures, transcripts and functions far more thorough in longevity, stress resistance and dauer formation. Acan-daf-16 encodes two proteins, Acan-DAF-16A and Acan-DAF-16B, consisting of 555 and 491 amino acids, respectively. Both isoforms possess the highly conserved fork head domains. Acan-daf-16A and Acan-daf-16B are expressed from distinct promoters. The expression patterns of Acan-daf-16 isoforms in the C. elegans surrogate system showed that p Acan-daf-16a:gfp was expressed in all cells of C. elegans, including the pharynx, and the expression of p Acan-daf-16b:gfp was restricted to the pharynx. In addition to the same genomic organization to the orthologue in C. elegans, Ce-daf-16, both Acan-DAF-16 isoforms could restore the C. elegans daf-16(mg54) mutation in longevity, dauer formation and stress resistance, in spite of the partial complementation of Acan-DAF-16B isoform in longevity. These findings provide further evidence of the functional conservation of DAF-16s between parasitic nematodes and the free-living nematode C. elegans. Copyright © 2016. Published by Elsevier B.V.

Identification of hookworm DAF-16/FOXO response elements and direct gene targets.

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Xin Gao

2010-08-01

Full Text Available The infective stage of the parasitic nematode hookworm is developmentally arrested in the environment and needs to infect a specific host to complete its life cycle. The canine hookworm (Ancylostoma caninum is an excellent model for investigating human hookworm infections. The transcription factor of A. caninum, Ac-DAF-16, which has a characteristic fork head or "winged helix" DNA binding domain (DBD, has been implicated in the resumption of hookworm development in the host. However, the precise roles of Ac-DAF-16 in hookworm parasitism and its downstream targets are unknown. In the present study, we combined molecular techniques and bioinformatics to identify a group of Ac-DAF-16 binding sites and target genes.The DNA binding domain of Ac-DAF-16 was used to select genomic fragments by in vitro genomic selection. Twenty four bound genomic fragments were analyzed for the presence of the DAF-16 family binding element (DBE and possible alternative Ac-DAF-16 bind motifs. The 22 genes linked to these genomic fragments were identified using bioinformatics tools and defined as candidate direct gene targets of Ac-DAF-16. Their developmental stage-specific expression patterns were examined. Also, a new putative DAF-16 binding element was identified.Our results show that Ac-DAF-16 is involved in diverse biological processes throughout hookworm development. Further investigation of these target genes will provide insights into the molecular basis by which Ac-DAF-16 regulates its downstream gene network in hookworm infection.

The MYST family histone acetyltransferase complex regulates stress resistance and longevity through transcriptional control of DAF-16/FOXO transcription factors.

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Ikeda, Takako; Uno, Masaharu; Honjoh, Sakiko; Nishida, Eisuke

2017-08-09

The well-known link between longevity and the Sir2 histone deacetylase family suggests that histone deacetylation, a modification associated with repressed chromatin, is beneficial to longevity. However, the molecular links between histone acetylation and longevity remain unclear. Here, we report an unexpected finding that the MYST family histone acetyltransferase complex (MYS-1/TRR-1 complex) promotes rather than inhibits stress resistance and longevity in Caenorhabditis elegans Our results show that these beneficial effects are largely mediated through transcriptional up-regulation of the FOXO transcription factor DAF-16. MYS-1 and TRR-1 are recruited to the promoter regions of the daf-16 gene, where they play a role in histone acetylation, including H4K16 acetylation. Remarkably, we also find that the human MYST family Tip60/TRRAP complex promotes oxidative stress resistance by up-regulating the expression of FOXO transcription factors in human cells. Tip60 is recruited to the promoter regions of the foxo1 gene, where it increases H4K16 acetylation levels. Our results thus identify the evolutionarily conserved role of the MYST family acetyltransferase as a key epigenetic regulator of DAF-16/FOXO transcription factors. © 2017 The Authors.

DAF-16 employs the chromatin remodeller SWI/SNF to promote stress resistance and longevity.

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Riedel, Christian G; Dowen, Robert H; Lourenco, Guinevere F; Kirienko, Natalia V; Heimbucher, Thomas; West, Jason A; Bowman, Sarah K; Kingston, Robert E; Dillin, Andrew; Asara, John M; Ruvkun, Gary

2013-05-01

Organisms are constantly challenged by stresses and privations and require adaptive responses for their survival. The forkhead box O (FOXO) transcription factor DAF-16 (hereafter referred to as DAF-16/FOXO) is a central nexus in these responses, but despite its importance little is known about how it regulates its target genes. Proteomic identification of DAF-16/FOXO-binding partners in Caenorhabditis elegans and their subsequent functional evaluation by RNA interference revealed several candidate DAF-16/FOXO cofactors, most notably the chromatin remodeller SWI/SNF. DAF-16/FOXO and SWI/SNF form a complex and globally co-localize at DAF-16/FOXO target promoters. We show that specifically for gene activation, DAF-16/FOXO depends on SWI/SNF, facilitating SWI/SNF recruitment to target promoters, to activate transcription by presumed remodelling of local chromatin. For the animal, this translates into an essential role for SWI/SNF in DAF-16/FOXO-mediated processes, in particular dauer formation, stress resistance and the promotion of longevity. Thus, we give insight into the mechanisms of DAF-16/FOXO-mediated transcriptional regulation and establish a critical link between ATP-dependent chromatin remodelling and lifespan regulation.

Cell-nonautonomous signaling of FOXO/DAF-16 to the stem cells of Caenorhabditis elegans.

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Wenjing Qi

Full Text Available In Caenorhabditis elegans (C. elegans, the promotion of longevity by the transcription factor DAF-16 requires reduced insulin/IGF receptor (IIR signaling or the ablation of the germline, although the reason for the negative impact of germ cells is unknown. FOXO/DAF-16 activity inhibits germline proliferation in both daf-2 mutants and gld-1 tumors. In contrast to its function as a germline tumor suppressor, we now provide evidence that somatic DAF-16 in the presence of IIR signaling can also result in tumorigenic activity, which counteracts robust lifespan extension. In contrast to the cell-autonomous IIR signaling, which is required for larval germline proliferation, activation of DAF-16 in the hypodermis results in hyperplasia of the germline and disruption of the surrounding basement membrane. SHC-1 adaptor protein and AKT-1 kinase antagonize, whereas AKT-2 and SGK-1 kinases promote, this cell-nonautonomous DAF-16 function. Our data suggest that a functional balance of DAF-16 activities in different tissues determines longevity and reveals a novel, cell-nonautonomous role of FOXO/DAF-16 to affect stem cells.

Cell-Nonautonomous Signaling of FOXO/DAF-16 to the Stem Cells of Caenorhabditis elegans

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Qi, Wenjing; Huang, Xu; Neumann-Haefelin, Elke; Schulze, Ekkehard; Baumeister, Ralf

2012-01-01

In Caenorhabditis elegans (C. elegans), the promotion of longevity by the transcription factor DAF-16 requires reduced insulin/IGF receptor (IIR) signaling or the ablation of the germline, although the reason for the negative impact of germ cells is unknown. FOXO/DAF-16 activity inhibits germline proliferation in both daf-2 mutants and gld-1 tumors. In contrast to its function as a germline tumor suppressor, we now provide evidence that somatic DAF-16 in the presence of IIR signaling can also result in tumorigenic activity, which counteracts robust lifespan extension. In contrast to the cell-autonomous IIR signaling, which is required for larval germline proliferation, activation of DAF-16 in the hypodermis results in hyperplasia of the germline and disruption of the surrounding basement membrane. SHC-1 adaptor protein and AKT-1 kinase antagonize, whereas AKT-2 and SGK-1 kinases promote, this cell-nonautonomous DAF-16 function. Our data suggest that a functional balance of DAF-16 activities in different tissues determines longevity and reveals a novel, cell-nonautonomous role of FOXO/DAF-16 to affect stem cells. PMID:22916022

The Deubiquitylase MATH-33 Controls DAF-16 Stability and Function in Metabolism and Longevity.

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Heimbucher, Thomas; Liu, Zheng; Bossard, Carine; McCloskey, Richard; Carrano, Andrea C; Riedel, Christian G; Tanasa, Bogdan; Klammt, Christian; Fonslow, Bryan R; Riera, Celine E; Lillemeier, Bjorn F; Kemphues, Kenneth; Yates, John R; O'Shea, Clodagh; Hunter, Tony; Dillin, Andrew

2015-07-07

FOXO family transcription factors are downstream effectors of Insulin/IGF-1 signaling (IIS) and major determinants of aging in organisms ranging from worms to man. The molecular mechanisms that actively promote DAF16/FOXO stability and function are unknown. Here we identify the deubiquitylating enzyme MATH-33 as an essential DAF-16 regulator in IIS, which stabilizes active DAF-16 protein levels and, as a consequence, influences DAF-16 functions, such as metabolism, stress response, and longevity in C. elegans. MATH-33 associates with DAF-16 in cellulo and in vitro. MATH-33 functions as a deubiquitylase by actively removing ubiquitin moieties from DAF-16, thus counteracting the action of the RLE-1 E3-ubiquitin ligase. Our findings support a model in which MATH-33 promotes DAF-16 stability in response to decreased IIS by directly modulating its ubiquitylation state, suggesting that regulated oscillations in the stability of DAF-16 protein play an integral role in controlling processes such as metabolism and longevity. Copyright © 2015 Elsevier Inc. All rights reserved.

RNA helicase HEL-1 promotes longevity by specifically activating DAF-16/FOXO transcription factor signaling in Caenorhabditis elegans

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Seo, Mihwa; Seo, Keunhee; Hwang, Wooseon; Koo, Hee Jung; Hahm, Jeong-Hoon; Yang, Jae-Seong; Han, Seong Kyu; Hwang, Daehee; Kim, Sanguk; Jang, Sung Key; Lee, Yoontae; Nam, Hong Gil; Lee, Seung-Jae V.

2015-01-01

The homeostatic maintenance of the genomic DNA is crucial for regulating aging processes. However, the role of RNA homeostasis in aging processes remains unknown. RNA helicases are a large family of enzymes that regulate the biogenesis and homeostasis of RNA. However, the functional significance of RNA helicases in aging has not been explored. Here, we report that a large fraction of RNA helicases regulate the lifespan of Caenorhabditis elegans. In particular, we show that a DEAD-box RNA helicase, helicase 1 (HEL-1), promotes longevity by specifically activating the DAF-16/forkhead box O (FOXO) transcription factor signaling pathway. We find that HEL-1 is required for the longevity conferred by reduced insulin/insulin-like growth factor 1 (IGF-1) signaling (IIS) and is sufficient for extending lifespan. We further show that the expression of HEL-1 in the intestine and neurons contributes to longevity. HEL-1 enhances the induction of a large fraction of DAF-16 target genes. Thus, the RNA helicase HEL-1 appears to promote longevity in response to decreased IIS as a transcription coregulator of DAF-16. Because HEL-1 and IIS are evolutionarily well conserved, a similar mechanism for longevity regulation via an RNA helicase-dependent regulation of FOXO signaling may operate in mammals, including humans. PMID:26195740

The C. elegans Ortholog of USP7 controls DAF-16 stability in Insulin/IGF-1-like signaling.

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Heimbucher, Thomas; Hunter, Tony

2015-01-01

FOXO family transcription factors are downstream effectors of Insulin/IGF-1 signaling (IIS) and are regulated by posttranslational modification and coregulators, including components of the ubiquitin-proteasome system (UPS). Cofactors promoting DAF-16/FOXO protein stability and function in IIS have not been described yet. In a recent study, we have identified the deubiquitylating enzyme MATH-33, the ortholog of mammalian USP7/HAUSP, as an essential DAF-16 coregulator. We found that MATH-33 actively stabilizes DAF-16 protein levels when IIS is downregulated. Here we discuss how DAF-16/FOXO transcription factors are regulated by the UPS, in particular by the interplay of E3-ubiquitin ligases and deubiquitylating enzymes, which is critical for balancing DAF-16/FOXO activity and degradation. Recent findings raise the intriguing possibility that regulated oscillations in DAF-16/FOXO steady state levels play an integral role in mechanisms controlling healthspan and lifespan extension.

Reversible reprotoxic effects of manganese through DAF-16 transcription factor activation and vitellogenin downregulation in Caenorhabditis elegans.

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Gubert, Priscila; Puntel, Bruna; Lehmen, Tassia; Bornhorst, Julia; Avila, Daiana S; Aschner, Michael; Soares, Felix A A

2016-04-15

Vitellogenesis is the yolk production process which provides the essential nutrients for the developing embryos. Yolk is a lipoprotein particle that presents lipids and lipid-binding proteins, referred to as vitellogenins (VIT). The Caenorhabditis elegans nematode has six genes encoding VIT lipoproteins. Several pathways are known to regulate vitellogenesis, including the DAF-16 transcription factor. Some reports have shown that heavy metals, such as manganese (Mn), impair brood size in C. elegans; however the mechanisms associated with this effect have yet to be identified. Our aim was to evaluate Mn's effects on C. elegans reproduction and better understand the pathways related to these effects. Young adult larval stage worms were treated for 4h with Mn in 85mM NaCl and Escherichia coli OP50 medium. Mn reduced egg-production and egg-laying during the first 24h after the treatment, although the total number of progenies were indistinguishable from the control group levels. This delay may have occurred due to DAF-16 activation, which was noted only after the treatment and was not apparent 24h later. Moreover, the expression, protein levels and green fluorescent protein (GFP) fluorescence associated with VIT were decreased soon after Mn treatment and recovered after 24h. Combined, these data suggest that the delay in egg-production is likely regulated by DAF-16 and followed by the inhibition of VIT transport activity. Further studies are needed to clarify the mechanisms associated with Mn-induced DAF-16 activation. Copyright © 2016 Elsevier Inc. All rights reserved.

DAF-16/FOXO employs the chromatin remodeller SWI/SNF to promote stress resistance and longevity

Science.gov (United States)

Riedel, Christian G.; Dowen, Robert H.; Lourenco, Guinevere F.; Kirienko, Natalia V.; Heimbucher, Thomas; West, Jason A.; Bowman, Sarah K.; Kingston, Robert E.; Dillin, Andrew; Asara, John M.; Ruvkun, Gary

2013-01-01

Organisms are constantly challenged by stresses and privations and require adaptive responses for their survival. The transcription factor DAF-16/FOXO is central nexus in these responses, but despite its importance little is known about how it regulates its target genes. Proteomic identification of DAF-16/FOXO binding partners in Caenorhabditis elegans and their subsequent functional evaluation by RNA interference (RNAi) revealed several candidate DAF-16/FOXO cofactors, most notably the chromatin remodeller SWI/SNF. DAF-16/FOXO and SWI/SNF form a complex and globally colocalize at DAF-16/FOXO target promoters. We show that specifically for gene-activation, DAF-16/FOXO depends on SWI/SNF, facilitating SWI/SNF recruitment to target promoters, in order to activate transcription by presumed remodelling of local chromatin. For the animal, this translates into an essential role of SWI/SNF for DAF-16/FOXO-mediated processes, i.e. dauer formation, stress resistance, and the promotion of longevity. Thus we give insight into the mechanisms of DAF-16/FOXO-mediated transcriptional regulation and establish a critical link between ATP-dependent chromatin remodelling and lifespan regulation. PMID:23604319

DAF-16/FOXO and EGL-27/GATA promote developmental growth in response to persistent somatic DNA damage.

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Mueller, Michael M; Castells-Roca, Laia; Babu, Vipin; Ermolaeva, Maria A; Müller, Roman-Ulrich; Frommolt, Peter; Williams, Ashley B; Greiss, Sebastian; Schneider, Jennifer I; Benzing, Thomas; Schermer, Bernhard; Schumacher, Björn

2014-12-01

Genome maintenance defects cause complex disease phenotypes characterized by developmental failure, cancer susceptibility and premature ageing. It remains poorly understood how DNA damage responses function during organismal development and maintain tissue functionality when DNA damage accumulates with ageing. Here we show that the FOXO transcription factor DAF-16 is activated in response to DNA damage during development, whereas the DNA damage responsiveness of DAF-16 declines with ageing. We find that in contrast to its established role in mediating starvation arrest, DAF-16 alleviates DNA-damage-induced developmental arrest and even in the absence of DNA repair promotes developmental growth and enhances somatic tissue functionality. We demonstrate that the GATA transcription factor EGL-27 co-regulates DAF-16 target genes in response to DNA damage and together with DAF-16 promotes developmental growth. We propose that EGL-27/GATA activity specifies DAF-16-mediated DNA damage responses to enable developmental progression and to prolong tissue functioning when DNA damage persists.

L1 arrest, daf-16/FoxO and nonautonomous control of post-embryonic development.

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Kaplan, Rebecca E W; Baugh, L Ryan

2016-01-01

Post-embryonic development is governed by nutrient availability. L1 arrest, dauer formation and aging illustrate how starvation, anticipation of starvation and caloric restriction have profound influence on C. elegans development, respectively. Insulin-like signaling through the Forkhead box O transcription factor daf-16/FoxO regulates each of these processes. We recently reported that ins-4, ins-6 and daf-28 promote L1 development from the intestine and chemosensory neurons, similar to their role in dauer development. daf-16 functions cell-nonautonomously in regulation of L1 arrest, dauer development and aging. Discrepancies in daf-16 sites of action have been reported in each context, but the consensus implicates epidermis, intestine and nervous system. We suggest technical limitations of the experimental approach responsible for discrepant results. Steroid hormone signaling through daf-12/NHR is known to function downstream of daf-16 in control of dauer development, but signaling pathways mediating cell-nonautonomous effects of daf-16 in aging and L1 arrest had not been identified. We recently showed that daf-16 promotes L1 arrest by inhibiting daf-12/NHR and dbl-1/TGF-β Sma/Mab signaling, two pathways that promote L1 development in fed larvae. We will review these results on L1 arrest and speculate on why there are so many signals and signaling centers regulating post-embryonic development.

DAF-16/FoxO directly regulates an atypical AMP-activated protein kinase gamma isoform to mediate the effects of insulin/IGF-1 signaling on aging in Caenorhabditis elegans.

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Jennifer M A Tullet

2014-02-01

Full Text Available The DAF-16/FoxO transcription factor controls growth, metabolism and aging in Caenorhabditis elegans. The large number of genes that it regulates has been an obstacle to understanding its function. However, recent analysis of transcript and chromatin profiling implies that DAF-16 regulates relatively few genes directly, and that many of these encode other regulatory proteins. We have investigated the regulation by DAF-16 of genes encoding the AMP-activated protein kinase (AMPK, which has α, β and γ subunits. C. elegans has 5 genes encoding putative AMP-binding regulatory γ subunits, aakg-1-5. aakg-4 and aakg-5 are closely related, atypical isoforms, with orthologs throughout the Chromadorea class of nematodes. We report that ∼75% of total γ subunit mRNA encodes these 2 divergent isoforms, which lack consensus AMP-binding residues, suggesting AMP-independent kinase activity. DAF-16 directly activates expression of aakg-4, reduction of which suppresses longevity in daf-2 insulin/IGF-1 receptor mutants. This implies that an increase in the activity of AMPK containing the AAKG-4 γ subunit caused by direct activation by DAF-16 slows aging in daf-2 mutants. Knock down of aakg-4 expression caused a transient decrease in activation of expression in multiple DAF-16 target genes. This, taken together with previous evidence that AMPK promotes DAF-16 activity, implies the action of these two metabolic regulators in a positive feedback loop that accelerates the induction of DAF-16 target gene expression. The AMPK β subunit, aakb-1, also proved to be up-regulated by DAF-16, but had no effect on lifespan. These findings reveal key features of the architecture of the gene-regulatory network centered on DAF-16, and raise the possibility that activation of AMP-independent AMPK in nutritionally replete daf-2 mutant adults slows aging in C. elegans. Evidence of activation of AMPK subunits in mammals suggests that such FoxO-AMPK interactions may be

DAF-16/FoxO directly regulates an atypical AMP-activated protein kinase gamma isoform to mediate the effects of insulin/IGF-1 signaling on aging in Caenorhabditis elegans.

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Tullet, Jennifer M A; Araiz, Caroline; Sanders, Matthew J; Au, Catherine; Benedetto, Alexandre; Papatheodorou, Irene; Clark, Emily; Schmeisser, Kathrin; Jones, Daniel; Schuster, Eugene F; Thornton, Janet M; Gems, David

2014-02-01

The DAF-16/FoxO transcription factor controls growth, metabolism and aging in Caenorhabditis elegans. The large number of genes that it regulates has been an obstacle to understanding its function. However, recent analysis of transcript and chromatin profiling implies that DAF-16 regulates relatively few genes directly, and that many of these encode other regulatory proteins. We have investigated the regulation by DAF-16 of genes encoding the AMP-activated protein kinase (AMPK), which has α, β and γ subunits. C. elegans has 5 genes encoding putative AMP-binding regulatory γ subunits, aakg-1-5. aakg-4 and aakg-5 are closely related, atypical isoforms, with orthologs throughout the Chromadorea class of nematodes. We report that ∼75% of total γ subunit mRNA encodes these 2 divergent isoforms, which lack consensus AMP-binding residues, suggesting AMP-independent kinase activity. DAF-16 directly activates expression of aakg-4, reduction of which suppresses longevity in daf-2 insulin/IGF-1 receptor mutants. This implies that an increase in the activity of AMPK containing the AAKG-4 γ subunit caused by direct activation by DAF-16 slows aging in daf-2 mutants. Knock down of aakg-4 expression caused a transient decrease in activation of expression in multiple DAF-16 target genes. This, taken together with previous evidence that AMPK promotes DAF-16 activity, implies the action of these two metabolic regulators in a positive feedback loop that accelerates the induction of DAF-16 target gene expression. The AMPK β subunit, aakb-1, also proved to be up-regulated by DAF-16, but had no effect on lifespan. These findings reveal key features of the architecture of the gene-regulatory network centered on DAF-16, and raise the possibility that activation of AMP-independent AMPK in nutritionally replete daf-2 mutant adults slows aging in C. elegans. Evidence of activation of AMPK subunits in mammals suggests that such FoxO-AMPK interactions may be evolutionarily conserved.

Baicalein modulates stress-resistance and life span in C. elegans via SKN-1 but not DAF-16.

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Havermann, Susannah; Humpf, Hans-Ulrich; Wätjen, Wim

2016-09-01

The flavonoid baicalein has been demonstrated to be an activator of the transcription factor Nrf2 in mammalian cell lines. We show that it further modulates the Nrf2 homolog SKN-1 in Caenorhabditis elegans and by this pathway mediates beneficial effects in the nematode: baicalein enhances the resistance of C. elegans against lethal thermal and sodium arsenite stress and dose-dependently prolongs the life span of the nematode. Using RNA interference against SKN-1 we were able to show that the induction of longevity and the enhanced stress-resistance were dependent on this transcription factor. DAF-16 (homolog to mammalian FOXO) is another pivotal aging-related transcription factor in the nematode. We demonstrate that DAF-16 does not participate in the beneficial effects of baicalein: since baicalein causes no increase in the nuclear translocation of DAF-16 (DAF-16::GFP expressing strain, incubation time: 1h) and it still induces longevity even in a DAF-16 loss-of-function strain, we conclude, that baicalein increases stress-resistance and life span in C. elegans via SKN-1 but not DAF-16. Copyright © 2016 Elsevier B.V. All rights reserved.

Synthetic DAF-12 modulators with potential use in controlling the nematode life cycle.

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Dansey, María V; Alvarez, Lautaro D; Samaja, Gisela; Escudero, Daiana S; Veleiro, Adriana S; Pecci, Adalí; Castro, Olga A; Burton, Gerardo

2015-01-01

Dafachronic acids (DAs) are 3-keto cholestenoic acids bearing a carboxylic acid moiety at the end of the steroid side chain. These compounds interact with the DAF-12 receptor, a ligand-dependent transcription factor that acts as a molecular switch mediating the choice between arrest at diapause or progression to reproductive development and adult lifespan in different nematodes. Recently, we reported that the 27-nor-Δ4-DA was able to directly activate DAF-12 in a transactivation cell-based luciferase assay and rescued the Mig phenotype of daf-9(rh50) Caenorhabditis elegans mutants. In the present paper, to investigate further the relationship between the structure of the steroid side chain and DAF-12 activity, we evaluated the in vitro and in vivo activity of Δ4-DA analogues with modified side chains using transactivation cell-based assays and daf-9(dh6) C. elegans mutants. Our results revealed that introduction of a 24,25-double bond on the cholestenoic acid side chain did not affect DAF-12 activity, whereas shortening the side chain lowered the activity. Most interestingly, the C24 alcohol 24-hydroxy-4-cholen-3-one (6) was an antagonist of the DAF-12 receptor both in vitro and in vivo.

The DAF-16 FOXO transcription factor regulates natc-1 to modulate stress resistance in Caenorhabditis elegans, linking insulin/IGF-1 signaling to protein N-terminal acetylation.

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Warnhoff, Kurt; Murphy, John T; Kumar, Sandeep; Schneider, Daniel L; Peterson, Michelle; Hsu, Simon; Guthrie, James; Robertson, J David; Kornfeld, Kerry

2014-10-01

The insulin/IGF-1 signaling pathway plays a critical role in stress resistance and longevity, but the mechanisms are not fully characterized. To identify genes that mediate stress resistance, we screened for C. elegans mutants that can tolerate high levels of dietary zinc. We identified natc-1, which encodes an evolutionarily conserved subunit of the N-terminal acetyltransferase C (NAT) complex. N-terminal acetylation is a widespread modification of eukaryotic proteins; however, relatively little is known about the biological functions of NATs. We demonstrated that loss-of-function mutations in natc-1 cause resistance to a broad-spectrum of physiologic stressors, including multiple metals, heat, and oxidation. The C. elegans FOXO transcription factor DAF-16 is a critical target of the insulin/IGF-1 signaling pathway that mediates stress resistance, and DAF-16 is predicted to directly bind the natc-1 promoter. To characterize the regulation of natc-1 by DAF-16 and the function of natc-1 in insulin/IGF-1 signaling, we analyzed molecular and genetic interactions with key components of the insulin/IGF-1 pathway. natc-1 mRNA levels were repressed by DAF-16 activity, indicating natc-1 is a physiological target of DAF-16. Genetic studies suggested that natc-1 functions downstream of daf-16 to mediate stress resistance and dauer formation. Based on these findings, we hypothesize that natc-1 is directly regulated by the DAF-16 transcription factor, and natc-1 is a physiologically significant effector of the insulin/IGF-1 signaling pathway that mediates stress resistance and dauer formation. These studies identify a novel biological function for natc-1 as a modulator of stress resistance and dauer formation and define a functionally significant downstream effector of the insulin/IGF-1 signaling pathway. Protein N-terminal acetylation mediated by the NatC complex may play an evolutionarily conserved role in regulating stress resistance.

The Transcription Factor DAF-16 is Essential for Increased Longevity in C. elegans Exposed to Bifidobacterium longum BB68.

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Zhao, Liang; Zhao, Yang; Liu, Ruihai; Zheng, Xiaonan; Zhang, Min; Guo, Huiyuan; Zhang, Hao; Ren, Fazheng

2017-08-07

The longevity-promoting benefits of lactobacilli were hypothesized as early as 1907. Although the anti-aging effects of lactic acid bacteria (LAB) have been observed in nematodes, rodents and humans for over a century, the mechanisms underlying the effects of probiotics on aging have rarely been assessed. Using the Caenorhabditis elegans (C. elegans) model, various studies have elucidated the role of different signaling cascades, especially the DAF-16 cascade, on lifespan extension by LAB. In this study, the mechanisms through which Bifidobacterium longum strain BB68 affects the longevity of C. elegans were assessed. The lifespan of nematodes increased by 28% after worms were fed BB68, and this extension of lifespan was completely lost in backgrounds containing a mutated DAF-16 gene. High levels of DAF-16 (in the daf-16 (mu86); muIs61 strain) nuclear accumulation and high expression of the SOD-3 gene (a DAF-16-specific target gene) were observed as a result of BB68 treatment. Immunofluorescence microscopy revealed that TIR-1 and JNK-1 are involved in the phosphorylation and activation of DAF-16. Thus, BB68 increased the longevity of nematodes by activating the TIR-1 - JNK-1 - DAF-16 signaling pathway, and the cell wall component of BB68 contributed to longevity.

daf-31 encodes the catalytic subunit of N alpha-acetyltransferase that regulates Caenorhabditis elegans development, metabolism and adult lifespan.

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Chen, Di; Zhang, Jiuli; Minnerly, Justin; Kaul, Tiffany; Riddle, Donald L; Jia, Kailiang

2014-10-01

The Caenorhabditis elegans dauer larva is a facultative state of diapause. Mutations affecting dauer signal transduction and morphogenesis have been reported. Of these, most that result in constitutive formation of dauer larvae are temperature-sensitive (ts). The daf-31 mutant was isolated in genetic screens looking for novel and underrepresented classes of mutants that form dauer and dauer-like larvae non-conditionally. Dauer-like larvae are arrested in development and have some, but not all, of the normal dauer characteristics. We show here that daf-31 mutants form dauer-like larvae under starvation conditions but are sensitive to SDS treatment. Moreover, metabolism is shifted to fat accumulation in daf-31 mutants. We cloned the daf-31 gene and it encodes an ortholog of the arrest-defective-1 protein (ARD1) that is the catalytic subunit of the major N alpha-acetyltransferase (NatA). A daf-31 promoter::GFP reporter gene indicates daf-31 is expressed in multiple tissues including neurons, pharynx, intestine and hypodermal cells. Interestingly, overexpression of daf-31 enhances the longevity phenotype of daf-2 mutants, which is dependent on the forkhead transcription factor (FOXO) DAF-16. We demonstrate that overexpression of daf-31 stimulates the transcriptional activity of DAF-16 without influencing its subcellular localization. These data reveal an essential role of NatA in controlling C. elegans life history and also a novel interaction between ARD1 and FOXO transcription factors, which may contribute to understanding the function of ARD1 in mammals.

Simulation environment architecture development using the DoDAF

NARCIS (Netherlands)

Berg, T. van den; Lutz, R.

2015-01-01

The US Department of Defense (DoD) Architecture Framework (DoDAF) provides a common approach for architecture description development. The primary use of DoDAF is capability development and system acquisition in the military domain. Although DoDAF was not designed to support the development of

DAF-16 employs the chromatin remodeller SWI/SNF to promote stress resistance and longevity

NARCIS (Netherlands)

Riedel, Christian G; Dowen, Robert H; Lourenco, Guinevere F; Kirienko, Natalia V; Heimbucher, Thomas; West, Jason A; Bowman, Sarah K; Kingston, Robert E; Dillin, Andrew; Asara, John M; Ruvkun, Gary

Organisms are constantly challenged by stresses and privations and require adaptive responses for their survival. The forkhead box O (FOXO) transcription factor DAF-16 (hereafter referred to as DAF-16/FOXO) is a central nexus in these responses, but despite its importance little is known about how

Insulin Signaling-independent Activation of DAF-16 Shapes the Transcriptome during Normal Aging

OpenAIRE

Zhang, Yan-Ping; Liang, Chung-Yi; Hsu, Ao-Lin; Li, Shang-Tong; Zhang, Pan; Dong, Meng-Qiu; Zhao, Han-Qing

2018-01-01

The roles and regulatory mechanisms of transriptome changes during aging are unclear. It has been proposed that the transcriptome suffers decay during aging owing to age-associated down-regulation of transcription factors. In this study, we characterized the role of a transcription factor DAF-16, which is a highly conserved lifespan regulator, in the normal aging process of Caenorhabditis elegans. We found that DAF-16 translocates into the nucleus in aged wild-type worms and activates the exp...

daf-31 encodes the catalytic subunit of N alpha-acetyltransferase that regulates Caenorhabditis elegans development, metabolism and adult lifespan.

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Di Chen

2014-10-01

Full Text Available The Caenorhabditis elegans dauer larva is a facultative state of diapause. Mutations affecting dauer signal transduction and morphogenesis have been reported. Of these, most that result in constitutive formation of dauer larvae are temperature-sensitive (ts. The daf-31 mutant was isolated in genetic screens looking for novel and underrepresented classes of mutants that form dauer and dauer-like larvae non-conditionally. Dauer-like larvae are arrested in development and have some, but not all, of the normal dauer characteristics. We show here that daf-31 mutants form dauer-like larvae under starvation conditions but are sensitive to SDS treatment. Moreover, metabolism is shifted to fat accumulation in daf-31 mutants. We cloned the daf-31 gene and it encodes an ortholog of the arrest-defective-1 protein (ARD1 that is the catalytic subunit of the major N alpha-acetyltransferase (NatA. A daf-31 promoter::GFP reporter gene indicates daf-31 is expressed in multiple tissues including neurons, pharynx, intestine and hypodermal cells. Interestingly, overexpression of daf-31 enhances the longevity phenotype of daf-2 mutants, which is dependent on the forkhead transcription factor (FOXO DAF-16. We demonstrate that overexpression of daf-31 stimulates the transcriptional activity of DAF-16 without influencing its subcellular localization. These data reveal an essential role of NatA in controlling C. elegans life history and also a novel interaction between ARD1 and FOXO transcription factors, which may contribute to understanding the function of ARD1 in mammals.

The DAF-7/TGF-β signaling pathway regulates abundance of the C. elegans glutamate receptor GLR-1

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McGehee, Annette M.; Moss, Benjamin J.; Juo, Peter

2015-01-01

Transforming growth factor-β (TGF-β) family signaling pathways have roles in both neuronal development and the regulation of synaptic function. Here we identify a novel role for the C. elegans DAF-7/TGF-β signaling pathway in the regulation of the AMPA-type glutamate receptor GLR-1. We found that the abundance of GLR-1 increases at synapses in the ventral nerve cord (VNC) of animals with loss-of-function mutations in multiple DAF-7/TGF-β pathway components including the TGF-β ligand DAF-7, the type I receptor DAF-1, and the Smads DAF-8 and DAF-14. The GLR-1 defect can be rescued by expression of daf-8 specifically in glr-1-expressing interneurons. The effect on GLR-1 was specific for the DAF-7 pathway because mutations in the DBL-1/TGF-β family pathway did not increase GLR-1 levels in the VNC. Immunoblot analysis indicates that total levels of GLR-1 protein are increased in neurons of DAF-7/TGF-β pathway mutants. The increased abundance of GLR-1 in the VNC of daf-7 pathway mutants is dependent on the transcriptional regulator DAF-3/Smad suggesting that DAF-3-dependent transcription controls GLR-1 levels. Furthermore, we found that glr-1 transcription is increased in daf-7 mutants based on a glr-1 transcriptional reporter. Together these results suggest that the DAF-7/TGF-β signaling pathway functions in neurons and negatively regulates the abundance of GLR-1, in part, by controlling transcription of the receptor itself. Finally, DAF-7/TGF-β pathway mutants exhibit changes in spontaneous locomotion that are dependent on endogenous GLR-1 and consistent with increased glutamatergic signaling. These results reveal a novel mechanism by which TGF-β signaling functions in the nervous system to regulate behavior. PMID:26054666

The DAF-7/TGF-β signaling pathway regulates abundance of the Caenorhabditis elegans glutamate receptor GLR-1.

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McGehee, Annette M; Moss, Benjamin J; Juo, Peter

2015-07-01

Transforming growth factor-β (TGF-β) family signaling pathways have roles in both neuronal development and the regulation of synaptic function. Here we identify a novel role for the Caenorhabditis elegans DAF-7/TGF-β signaling pathway in the regulation of the AMPA-type glutamate receptor GLR-1. We found that the abundance of GLR-1 increases at synapses in the ventral nerve cord (VNC) of animals with loss-of-function mutations in multiple DAF-7/TGF-β pathway components including the TGF-β ligand DAF-7, the type I receptor DAF-1, and the Smads DAF-8 and DAF-14. The GLR-1 defect can be rescued by expression of daf-8 specifically in glr-1-expressing interneurons. The effect on GLR-1 was specific for the DAF-7 pathway because mutations in the DBL-1/TGF-β family pathway did not increase GLR-1 levels in the VNC. Immunoblot analysis indicates that total levels of GLR-1 protein are increased in neurons of DAF-7/TGF-β pathway mutants. The increased abundance of GLR-1 in the VNC of daf-7 pathway mutants is dependent on the transcriptional regulator DAF-3/Smad suggesting that DAF-3-dependent transcription controls GLR-1 levels. Furthermore, we found that glr-1 transcription is increased in daf-7 mutants based on a glr-1 transcriptional reporter. Together these results suggest that the DAF-7/TGF-β signaling pathway functions in neurons and negatively regulates the abundance of GLR-1, in part, by controlling transcription of the receptor itself. Finally, DAF-7/TGF-β pathway mutants exhibit changes in spontaneous locomotion that are dependent on endogenous GLR-1 and consistent with increased glutamatergic signaling. These results reveal a novel mechanism by which TGF-β signaling functions in the nervous system to regulate behavior. Copyright © 2015 Elsevier Inc. All rights reserved.

The protein kinase MBK-1 contributes to lifespan extension in daf-2 mutant and germline-deficient Caenorhabditis elegans.

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Mack, Hildegard I D; Zhang, Peichuan; Fonslow, Bryan R; Yates, John R

2017-05-25

In Caenorhabditis elegans , reduction of insulin/IGF-1 like signaling and loss of germline stem cells both increase lifespan by activating the conserved transcription factor DAF-16 (FOXO). While the mechanisms that regulate DAF-16 nuclear localization in response to insulin/IGF-1 like signaling are well characterized, the molecular pathways that act in parallel to regulate DAF-16 transcriptional activity, and the pathways that couple DAF-16 activity to germline status, are not fully understood at present. Here, we report that inactivation of MBK-1, the C. elegans ortholog of the human FOXO1-kinase DYRK1A substantially shortens the prolonged lifespan of daf-2 and glp-1 mutant animals while decreasing wild-type lifespan to a lesser extent. On the other hand, lifespan-reduction by mutation of the MBK-1-related kinase HPK-1 was not preferential for long-lived mutants. Interestingly, mbk-1 loss still allowed for DAF-16 nuclear accumulation but reduced expression of certain DAF-16 target genes in germline-less, but not in daf-2 mutant animals. These findings indicate that mbk-1 and daf-16 functionally interact in the germline- but not in the daf-2 pathway. Together, our data suggest mbk-1 as a novel regulator of C. elegans longevity upon both, germline ablation and DAF-2 inhibition, and provide evidence for mbk-1 regulating DAF-16 activity in germline-deficient animals.

The DAF-16 FOXO transcription factor regulates natc-1 to modulate stress resistance in Caenorhabditis elegans, linking insulin/IGF-1 signaling to protein N-terminal acetylation.

Directory of Open Access Journals (Sweden)

Kurt Warnhoff

2014-10-01

Full Text Available The insulin/IGF-1 signaling pathway plays a critical role in stress resistance and longevity, but the mechanisms are not fully characterized. To identify genes that mediate stress resistance, we screened for C. elegans mutants that can tolerate high levels of dietary zinc. We identified natc-1, which encodes an evolutionarily conserved subunit of the N-terminal acetyltransferase C (NAT complex. N-terminal acetylation is a widespread modification of eukaryotic proteins; however, relatively little is known about the biological functions of NATs. We demonstrated that loss-of-function mutations in natc-1 cause resistance to a broad-spectrum of physiologic stressors, including multiple metals, heat, and oxidation. The C. elegans FOXO transcription factor DAF-16 is a critical target of the insulin/IGF-1 signaling pathway that mediates stress resistance, and DAF-16 is predicted to directly bind the natc-1 promoter. To characterize the regulation of natc-1 by DAF-16 and the function of natc-1 in insulin/IGF-1 signaling, we analyzed molecular and genetic interactions with key components of the insulin/IGF-1 pathway. natc-1 mRNA levels were repressed by DAF-16 activity, indicating natc-1 is a physiological target of DAF-16. Genetic studies suggested that natc-1 functions downstream of daf-16 to mediate stress resistance and dauer formation. Based on these findings, we hypothesize that natc-1 is directly regulated by the DAF-16 transcription factor, and natc-1 is a physiologically significant effector of the insulin/IGF-1 signaling pathway that mediates stress resistance and dauer formation. These studies identify a novel biological function for natc-1 as a modulator of stress resistance and dauer formation and define a functionally significant downstream effector of the insulin/IGF-1 signaling pathway. Protein N-terminal acetylation mediated by the NatC complex may play an evolutionarily conserved role in regulating stress resistance.

Ida-1, the Caenorhabditis elegans orthologue of mammalian diabetes autoantigen IA-2, potentially acts as a common modulator between Parkinson's disease and Diabetes: role of Daf-2/Daf-16 insulin like signalling pathway.

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Fatima, Soobiya; Haque, Rizwanul; Jadiya, Pooja; Shamsuzzama; Kumar, Lalit; Nazir, Aamir

2014-01-01

The lack of cure to age associated Parkinson's disease (PD) has been challenging the efforts of researchers as well as health care providers. Recent evidences suggest that diabetic patients tend to show a higher future risk for PD advocating a strong correlation between PD and Diabetes, thus making it intriguing to decipher common genetic cues behind these ailments. We carried out studies on ida-1, the C. elegans orthologue of mammalian type-1 diabetes auto-antigen IA-2 towards achieving its functional workup vis-à-vis various associated endpoints of PD and Diabetes. Employing transgenic C. elegans strain expressing "human" alpha synuclein (NL5901) under normal and increased glucose concentrations, we studied aggregation of alpha synuclein, content of dopamine, expression of dopamine transporter, content of reactive oxygen species, locomotor activity, nuclear translocation of FOXO transcription factor Daf-16, and quantification of Daf2/Daf-16 mRNA. Our findings indicate that ida-1 affords protection in the studied disease conditions as absence of ida-1 resulted in higher alpha-synuclein aggregation under conditions that mimic the blood glucose levels of diabetic patients. We also observed reduced dopamine content, decreased motility, defective Daf-16 translocation and reduced expression of Daf-2 and Daf-16. Our studies establish important function of ida-1 as a modulator in Daf-2/Daf-16 insulin like signalling pathway thus possibly being a common link between PD and Diabetes.

Genome-wide endogenous DAF-16/FOXO recruitment dynamics during lowered insulin signalling in C. elegans.

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Kumar, Neeraj; Jain, Vaibhav; Singh, Anupama; Jagtap, Urmila; Verma, Sonia; Mukhopadhyay, Arnab

2015-12-08

Lowering insulin-IGF-1-like signalling (IIS) activates FOXO transcription factors (TF) to extend life span across species. To study the dynamics of FOXO chromatin occupancy under this condition in C. elegans, we report the first recruitment profile of endogenous DAF-16 and show that the response is conserved. DAF-16 predominantly acts as a transcriptional activator and binding within the 0.5 kb promoter-proximal region results in maximum induction of downstream targets that code for proteins involved in detoxification and longevity. Interestingly, genes that are activated under low IIS already have higher DAF-16 recruited to their promoters in WT. DAF-16 binds to variants of the FOXO consensus sequence in the promoter proximal regions of genes that are exclusively targeted during low IIS. We also define a set of 'core' direct targets, after comparing multiple studies, which tend to co-express and contribute robustly towards IIS-associated phenotypes. Additionally, we show that nuclear hormone receptor DAF-12 as well as zinc-finger TF EOR-1 may bind DNA in close proximity to DAF-16 and distinct TF classes that are direct targets of DAF-16 may be instrumental in regulating its indirect targets. Together, our study provides fundamental insights into the transcriptional biology of FOXO/DAF-16 and gene regulation downstream of the IIS pathway.

C. elegans SIRT6/7 homolog SIR-2.4 promotes DAF-16 relocalization and function during stress.

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Chiang, Wei-Chung; Tishkoff, Daniel X; Yang, Bo; Wilson-Grady, Joshua; Yu, Xiaokun; Mazer, Travis; Eckersdorff, Mark; Gygi, Steven P; Lombard, David B; Hsu, Ao-Lin

2012-09-01

FoxO transcription factors and sirtuin family deacetylases regulate diverse biological processes, including stress responses and longevity. Here we show that the Caenorhabditis elegans sirtuin SIR-2.4--homolog of mammalian SIRT6 and SIRT7 proteins--promotes DAF-16-dependent transcription and stress-induced DAF-16 nuclear localization. SIR-2.4 is required for resistance to multiple stressors: heat shock, oxidative insult, and proteotoxicity. By contrast, SIR-2.4 is largely dispensable for DAF-16 nuclear localization and function in response to reduced insulin/IGF-1-like signaling. Although acetylation is known to regulate localization and activity of mammalian FoxO proteins, this modification has not been previously described on DAF-16. We find that DAF-16 is hyperacetylated in sir-2.4 mutants. Conversely, DAF-16 is acetylated by the acetyltransferase CBP-1, and DAF-16 is hypoacetylated and constitutively nuclear in response to cbp-1 inhibition. Surprisingly, a SIR-2.4 catalytic mutant efficiently rescues the DAF-16 localization defect in sir-2.4 null animals. Acetylation of DAF-16 by CBP-1 in vitro is inhibited by either wild-type or mutant SIR-2.4, suggesting that SIR-2.4 regulates DAF-16 acetylation indirectly, by preventing CBP-1-mediated acetylation under stress conditions. Taken together, our results identify SIR-2.4 as a critical regulator of DAF-16 specifically in the context of stress responses. Furthermore, they reveal a novel role for acetylation, modulated by the antagonistic activities of CBP-1 and SIR-2.4, in modulating DAF-16 localization and function.

Towards understanding the lifespan extension by reduced insulin signaling: bioinformatics analysis of DAF-16/FOXO direct targets in Caenorhabditis elegans.

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Li, Yan-Hui; Zhang, Gai-Gai

2016-04-12

DAF-16, the C. elegans FOXO transcription factor, is an important determinant in aging and longevity. In this work, we manually curated FOXODB http://lyh.pkmu.cn/foxodb/, a database of FOXO direct targets. It now covers 208 genes. Bioinformatics analysis on 109 DAF-16 direct targets in C. elegans found interesting results. (i) DAF-16 and transcription factor PQM-1 co-regulate some targets. (ii) Seventeen targets directly regulate lifespan. (iii) Four targets are involved in lifespan extension induced by dietary restriction. And (iv) DAF-16 direct targets might play global roles in lifespan regulation.

Selenite protects Caenorhabditis elegans from oxidative stress via DAF-16 and TRXR-1.

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Li, Wen-Hsuan; Shi, Yeu-Ching; Chang, Chun-Han; Huang, Chi-Wei; Hsiu-Chuan Liao, Vivian

2014-04-01

Selenium is an essential micronutrient. In the present study, trace amount of selenite (0.01 μM) was evaluated for oxidative stress resistance and potential associated factors in Caenorhabditis elegans. Selenite-treated C. elegans showed an increased survival under oxidative stress and thermal stress compared to untreated controls. Further studies demonstrated that the significant stress resistance of selenite on C. elegans could be attributed to its in vivo free radical-scavenging ability. We also found that the oxidative and thermal stress resistance phenotypes by selenite were absent from the forkhead transcription factor daf-16 mutant worms. Moreover, selenite influenced the subcellular distribution of DAF-16 in C. elegans. Furthermore, selenite increased mRNA levels of stress-resistance-related proteins, including superoxide dismutase-3 and heat shock protein-16.2. Additionally, selenite (0.01 μM) upregulated expressions of transgenic C. elegans carrying sod-3::green fluorescent protein (GFP) and hsp-16.2::GFP, whereas this effect was abolished by feeding daf-16 RNA interference in C. elegans. Finally, unlike the wild-type N2 worms, the oxidative stress resistance phenotypes by selenite were both absent from the C. elegans selenoprotein trxr-1 mutant worms and trxr-1 mutants feeding with daf-16 RNA interference. These findings suggest that the antioxidant effects of selenite in C. elegans are mediated via DAF-16 and TRXR-1. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Nonautonomous Regulation of Neuronal Migration by Insulin Signaling, DAF-16/FOXO, and PAK-1

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Lisa M. Kennedy

2013-09-01

Full Text Available Neuronal migration is essential for nervous system development in all organisms and is regulated in the nematode, C. elegans, by signaling pathways that are conserved in humans. Here, we demonstrate that the insulin/IGF-1-PI3K signaling pathway modulates the activity of the DAF-16/FOXO transcription factor to regulate the anterior migrations of the hermaphrodite-specific neurons (HSNs during embryogenesis of C. elegans. When signaling is reduced, DAF-16 is activated and promotes migration; conversely, when signaling is enhanced, DAF-16 is inactivated, and migration is inhibited. We show that DAF-16 acts nonautonomously in the hypodermis to promote HSN migration. Furthermore, we identify PAK-1, a p21-activated kinase, as a downstream mediator of insulin/IGF-1-DAF-16 signaling in the nonautonomous control of HSN migration. Because a FOXO-Pak1 pathway was recently shown to regulate mammalian neuronal polarity, our findings indicate that the roles of FOXO and Pak1 in neuronal migration are most likely conserved from C. elegans to higher organisms.

Acoustic sensitivity of the saccule and daf music.

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Emami, Seyede Faranak

2014-04-01

The daf is a large Persian frame drum used as a musical instrument in both popular and classical music which can induce a percussive sound at low frequencies (146-290 Hz) with peaks of up to 130 dBspl. The percussive sounds have a power distribution in the region of saccular sensitivity. In view of the saccular stimulation by sound in humans, we decided to use cervical vestibular-evoked myogenic potentials (cVEMPs) to evaluate the possibility that the daf music may have a disturbing effect on saccular function. During this case-control study, 18 daf musicians were compared with 20 healthy individuals evaluated in the audiology department of the Hamadan University of Medical Sciences. Assessment consisted of pure tone audiometry, tympanometry, and cVEMPs. Multiple comparisons of mean the cVEMPs and mean hearing loss at 250 Hz among the three groups (affected, unaffected, and normal ears) were significant. There were no significant differences between all daf players on high-tone loss at 3000 Hz. The daf musicians had bilateral unsymmetrical sensorineural hearing loss (SNHL), with hearing loss at 250 Hz (low-tone loss) and notched audiogram at 3000 Hz (high-tone loss). Eleven musicians with decreased vestibular excitability as detected by abnormal cVEMPs had mild (26-40 dBHL) low-tone loss and significant abnormal cVEMPs findings. In contrast, the others had slight (16-25 dBHL) low-tone loss with normal cVEMPs. Exposure to daf music is related to both saccular and cochlear dysfunction. Exposure to daf music is related to both saccular and cochlear dysfunction.

Regulation of Lysosomal Function by the DAF-16 Forkhead Transcription Factor Couples Reproduction to Aging in Caenorhabditis elegans.

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Baxi, Kunal; Ghavidel, Ata; Waddell, Brandon; Harkness, Troy A; de Carvalho, Carlos E

2017-09-01

Aging in eukaryotes is accompanied by widespread deterioration of the somatic tissue. Yet, abolishing germ cells delays the age-dependent somatic decline in Caenorhabditis elegans In adult worms lacking germ cells, the activation of the DAF-9/DAF-12 steroid signaling pathway in the gonad recruits DAF-16 activity in the intestine to promote longevity-associated phenotypes. However, the impact of this pathway on the fitness of normally reproducing animals is less clear. Here, we explore the link between progeny production and somatic aging and identify the loss of lysosomal acidity-a critical regulator of the proteolytic output of these organelles-as a novel biomarker of aging in C. elegans The increase in lysosomal pH in older worms is not a passive consequence of aging, but instead is timed with the cessation of reproduction, and correlates with the reduction in proteostasis in early adult life. Our results further implicate the steroid signaling pathway and DAF-16 in dynamically regulating lysosomal pH in the intestine of wild-type worms in response to the reproductive cycle. In the intestine of reproducing worms, DAF-16 promotes acidic lysosomes by upregulating the expression of v-ATPase genes. These findings support a model in which protein clearance in the soma is linked to reproduction in the gonad via the active regulation of lysosomal acidification. Copyright © 2017 by the Genetics Society of America.

Non-transcriptional Function of FOXO1/DAF-16 Contributes to Translesion DNA Synthesis.

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Daitoku, Hiroaki; Kaneko, Yuta; Yoshimochi, Kenji; Matsumoto, Kaori; Araoi, Sho; Sakamaki, Jun-Ichi; Takahashi, Yuta; Fukamizu, Akiyoshi

2016-08-22

Forkhead box O (FOXO; DAF-16 in nematode) transcription factors activate a program of genes that control stress resistance, metabolism, and lifespan. Given the adverse impact of the stochastic DNA damage on organismal development and ageing, we examined the role of FOXO/DAF-16 in UV-induced DNA-damage response. Knockdown of FOXO1, but not FOXO3a, increases sensitivity to UV irradiation when exposed during S phase, suggesting a contribution of FOXO1 to translesion DNA synthesis (TLS), a replicative bypass of UV-induced DNA lesions. Actually, FOXO1 depletion results in a sustained activation of the ATR-Chk1 signaling and a reduction of PCNA monoubiquitination following UV irradiation. FOXO1 does not alter the expression of TLS-related genes but binds to the protein replication protein A (RPA1) that coats single-stranded DNA and acts as a scaffold for TLS. In Caenorhabditis elegans, daf-16 null mutants show UV-induced retardation in larval development and are rescued by overexpressing DAF-16 mutant lacking transactivation domain, but not substitution mutant unable to interact with RPA-1. Thus, our findings demonstrate that FOXO1/DAF-16 is a functional component in TLS independently of its transactivation activity. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Non-autonomous Regulation of Neuronal Migration by Insulin Signaling, DAF-16/FOXO and PAK-1

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Kennedy, Lisa M.; Pham, Steven C.D.L.; Grishok, Alla

2013-01-01

SUMMARY Neuronal migration is essential for nervous system development in all organisms and is regulated in the nematode, C. elegans, by signaling pathways that are conserved in humans. Here, we demonstrate that the Insulin/IGF-1-PI3K signaling pathway modulates the activity of the DAF-16/FOXO transcription factor to promote the anterior migrations of the hermaphrodite-specific neurons (HSNs) during embryogenesis of C. elegans. When signaling is reduced, DAF-16 is activated and promotes migration, conversely, when signaling is enhanced, DAF-16 is inactivated and migration is inhibited. We show that DAF-16 acts non-autonomously in the hypodermis to promote HSN migration. Furthermore, we identify PAK-1, a p21-activated kinase, as a downstream mediator of Insulin/IGF-1-DAF-16 signaling in the non-autonomous control of HSN migration. As a FOXO-Pak1 pathway was recently shown to regulate mammalian neuronal polarity, our findings indicate that the roles of FOXO and Pak1 in neuronal migration are likely conserved from C. elegans to higher organisms. PMID:23994474

Functional Conservation and Divergence of daf-22 Paralogs in Pristionchus pacificus Dauer Development.

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Markov, Gabriel V; Meyer, Jan M; Panda, Oishika; Artyukhin, Alexander B; Claaßen, Marc; Witte, Hanh; Schroeder, Frank C; Sommer, Ralf J

2016-10-01

Small-molecule signaling in nematode dauer formation has emerged as a major model to study chemical communication in development and evolution. Developmental arrest as nonfeeding and stress-resistant dauer larvae represents the major survival and dispersal strategy. Detailed studies in Caenorhabditis elegans and Pristionchus pacificus revealed that small-molecule communication changes rapidly in evolution resulting in extreme structural diversity of small-molecule compounds. In C. elegans, a blend of ascarosides constitutes the dauer pheromone, whereas the P. pacificus dauer pheromone includes additional paratosides and integrates building blocks from diverse primary metabolic pathways. Despite this complexity of small-molecule structures and functions, little is known about the biosynthesis of small molecules in nematodes outside C. elegans Here, we show that the genes encoding enzymes of the peroxisomal β-oxidation pathway involved in small-molecule biosynthesis evolve rapidly, including gene duplications and domain switching. The thiolase daf-22, the most downstream factor in C. elegans peroxisomal β-oxidation, has duplicated in P. pacificus, resulting in Ppa-daf-22.1, which still contains the sterol-carrier-protein (SCP) domain that was lost in C. elegans daf-22, and Ppa-daf-22.2. Using the CRISPR/Cas9 system, we induced mutations in both P. pacificus daf-22 genes and identified an unexpected complexity of functional conservation and divergence. Under well-fed conditions, ascaroside biosynthesis proceeds exclusively via Ppa-daf-22.1 In contrast, starvation conditions induce Ppa-daf-22.2 activity, resulting in the production of a specific subset of ascarosides. Gene expression studies indicate a reciprocal up-regulation of both Ppa-daf-22 genes, which is, however, independent of starvation. Thus, our study reveals an unexpected functional complexity of dauer development and evolution. © The Author 2016. Published by Oxford University Press on behalf of the

Data Analysis Facility (DAF)

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1991-01-01

NASA-Dryden's Data Analysis Facility (DAF) provides a variety of support services to the entire Dryden community. It provides state-of-the-art hardware and software systems, available to any Dryden engineer for pre- and post-flight data processing and analysis, plus supporting all archival and general computer use. The Flight Data Access System (FDAS) is one of the advanced computer systems in the DAF, providing for fast engineering unit conversion and archival processing of flight data delivered from the Western Aeronautical Test Range. Engineering unit conversion and archival formatting of flight data is performed by the DRACO program on a Sun 690MP and an E-5000 computer. Time history files produced by DRACO are then moved to a permanent magneto-optical archive, where they are network-accessible 24 hours a day, 7 days a week. Pertinent information about the individual flights is maintained in a relational (Sybase) database. The DAF also houses all general computer services, including; the Compute Server 1 and 2 (CS1 and CS2), the server for the World Wide Web, overall computer operations support, courier service, a CD-ROM Writer system, a Technical Support Center, the NASA Dryden Phone System (NDPS), and Hardware Maintenance.

Dianxianning improved amyloid β-induced pathological characteristics partially through DAF-2/DAF-16 insulin like pathway in transgenic C. elegans.

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Zhi, Dejuan; Wang, Dong; Yang, Wenqi; Duan, Ziyun; Zhu, Shuqian; Dong, Juan; Wang, Na; Wang, Ningbo; Fei, Dongqing; Zhang, Zhanxin; Wang, Xin; Wang, Meizhu; Li, Hongyu

2017-09-12

Dianxianning (DXN) is a traditional Chinese formula, and has been approved in China for treating epilepsy since 1996. Here anti-Alzheimer's disease activity of DXN has been reported. DXN improved AD-like symptoms of paralysis and 5-HT sensitivity of transgenic Aβ 1-42 C. elegans. In worms, DXN significantly increased Aβ monomers and decreased the toxic Aβ oligomers, thus reducing Aβ toxicity. DXN significantly suppressed the expression of hsp-16.2 induced by juglone, and up-regulated sod-3 expression. These results indicated that DXN increased stress resistance and protected C. elegans against oxidative stress. Furthermore, DXN could significantly promote DAF-16 nuclear translocation, but it did not activate SKN-1. The inhibitory effect of DXN on the Aβ toxicity was significantly reverted by daf-16 RNAi, rather than skn-1 RNAi or hsf-1 RNAi. These results indicated that DAF-16 is at least partially required for the anti-AD effect of DXN. In conclusion, DXN improved Aβ-induced pathological characteristics partially through DAF-2/DAF-16 insulin like pathway in transgenic worms. Together with our data obtained by Morris water maze test, the results showed that DXN markedly ameliorated cognitive performance impairment induced by scopolamine in mice. All the results support that DXN is a potential drug candidate to treat Alzheimer's diseases.

DAF-12 Regulates a Connected Network of Genes to Ensure Robust Developmental Decisions

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Stuckenholz, Carsten; Labhart, Paul; Alexiadis, Vassili; Martin, René; Knölker, Hans-Joachim; Fisher, Alfred L.

2011-01-01

The nuclear receptor DAF-12 has roles in normal development, the decision to pursue dauer development in unfavorable conditions, and the modulation of adult aging. Despite the biologic importance of DAF-12, target genes for this receptor are largely unknown. To identify DAF-12 targets, we performed chromatin immunoprecipitation followed by hybridization to whole-genome tiling arrays. We identified 1,175 genomic regions to be bound in vivo by DAF-12, and these regions are enriched in known DAF-12 binding motifs and act as DAF-12 response elements in transfected cells and in transgenic worms. The DAF-12 target genes near these binding sites include an extensive network of interconnected heterochronic and microRNA genes. We also identify the genes encoding components of the miRISC, which is required for the control of target genes by microRNA, as a target of DAF-12 regulation. During reproductive development, many of these target genes are misregulated in daf-12(0) mutants, but this only infrequently results in developmental phenotypes. In contrast, we and others have found that null daf-12 mutations enhance the phenotypes of many miRISC and heterochronic target genes. We also find that environmental fluctuations significantly strengthen the weak heterochronic phenotypes of null daf-12 alleles. During diapause, DAF-12 represses the expression of many heterochronic and miRISC target genes, and prior work has demonstrated that dauer formation can suppress the heterochronic phenotypes of many of these target genes in post-dauer development. Together these data are consistent with daf-12 acting to ensure developmental robustness by committing the animal to adult or dauer developmental programs despite variable internal or external conditions. PMID:21814518

Effects of Caenorhabditis elegans sgk-1 mutations on lifespan, stress resistance, and DAF-16/FoxO regulation.

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Chen, Albert Tzong-Yang; Guo, Chunfang; Dumas, Kathleen J; Ashrafi, Kaveh; Hu, Patrick J

2013-10-01

The AGC family serine-threonine kinases Akt and Sgk are similar in primary amino acid sequence and in vitro substrate specificity, and both kinases are thought to directly phosphorylate and inhibit FoxO transcription factors. In the nematode Caenorhabditis elegans, it is well established that AKT-1 controls dauer arrest and lifespan by regulating the subcellular localization of the FoxO transcription factor DAF-16. SGK-1 is thought to act similarly to AKT-1 in lifespan control by phosphorylating and inhibiting the nuclear translocation of DAF-16/FoxO. Using sgk-1 null and gain-of-function mutants, we now provide multiple lines of evidence indicating that AKT-1 and SGK-1 influence C. elegans lifespan, stress resistance, and DAF-16/FoxO activity in fundamentally different ways. Whereas AKT-1 shortens lifespan, SGK-1 promotes longevity in a DAF-16-/FoxO-dependent manner. In contrast to AKT-1, which reduces resistance to multiple stresses, SGK-1 promotes resistance to oxidative stress and ultraviolet radiation but inhibits thermotolerance. Analysis of several DAF-16/FoxO target genes that are repressed by AKT-1 reveals that SGK-1 represses a subset of these genes while having little influence on the expression of others. Accordingly, unlike AKT-1, which promotes the cytoplasmic sequestration of DAF-16/FoxO, SGK-1 does not influence DAF-16/FoxO subcellular localization. Thus, in spite of their similar in vitro substrate specificities, Akt and Sgk influence longevity, stress resistance, and FoxO activity through distinct mechanisms in vivo. Our findings highlight the need for a re-evaluation of current paradigms of FoxO regulation by Sgk. © 2013 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

RNAi screen of DAF-16/FOXO target genes in C. elegans links pathogenesis and dauer formation.

Directory of Open Access Journals (Sweden)

Victor L Jensen

2010-12-01

Full Text Available The DAF-16/FOXO transcription factor is the major downstream output of the insulin/IGF1R signaling pathway controlling C. elegans dauer larva development and aging. To identify novel downstream genes affecting dauer formation, we used RNAi to screen candidate genes previously identified to be regulated by DAF-16. We used a sensitized genetic background [eri-1(mg366; sdf-9(m708], which enhances both RNAi efficiency and constitutive dauer formation (Daf-c. Among 513 RNAi clones screened, 21 displayed a synthetic Daf-c (SynDaf phenotype with sdf-9. One of these genes, srh-100, was previously identified to be SynDaf, but twenty have not previously been associated with dauer formation. Two of the latter genes, lys-1 and cpr-1, are known to participate in innate immunity and six more are predicted to do so, suggesting that the immune response may contribute to the dauer decision. Indeed, we show that two of these genes, lys-1 and clc-1, are required for normal resistance to Staphylococcus aureus. clc-1 is predicted to function in epithelial cohesion. Dauer formation exhibited by daf-8(m85, sdf-9(m708, and the wild-type N2 (at 27°C were all enhanced by exposure to pathogenic bacteria, while not enhanced in a daf-22(m130 background. We conclude that knockdown of the genes required for proper pathogen resistance increases pathogenic infection, leading to increased dauer formation in our screen. We propose that dauer larva formation is a behavioral response to pathogens mediated by increased dauer pheromone production.

Myricetin-Mediated Lifespan Extension in Caenorhabditis elegans Is Modulated by DAF-16

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Wim Wätjen

2013-06-01

Full Text Available Myricetin is a naturally occurring flavonol found in many plant based food sources. It increases the lifespan of Caenorhabditis elegans, but the molecular mechanisms are not yet fully understood. We have investigated the impact of this flavonoid on the transcription factors DAF-16 (C. elegans FoxO homologue and SKN-1 (Nrf2 homologue, which have crucial functions in the regulation of ageing. Myricetin is rapidly assimilated by the nematode, causes a nuclear translocation of DAF-16 but not of SKN-1, and finally prolongs the mean adult lifespan of C. elegans by 32.9%. The lifespan prolongation was associated with a decrease in the accumulation of reactive oxygen species (ROS detected by DCF. Myricetin also decreases the formation of lipofuscin, a pigment consisting of highly oxidized and cross-linked proteins that is considered as a biomarker of ageing in diverse species. The lifespan extension was completely abolished in a daf-16 loss-of-function mutant strain (CF1038. Consistently with this result, myricetin was also not able to diminish stress-induced ROS accumulation in the mutant. These results strongly indicate that the pro-longevity effect of myricetin is dependent on DAF-16 and not on direct anti-oxidative effects of the flavonoid.

Localization of Nitric Oxide in Wheat Roots by DAF Fluorescence.

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Wany, Aakanksha; Gupta, Kapuganti Jagadis

2016-01-01

Nitric oxide is a free radical signal molecule. Various methods are available for measurement of NO. Out of all methods, fluorescent probes to localize NO is very widely used method. Diaminofluorescein in diacetate form (DAF-2DA) is most widely probe for NO measurement. This method is based on application of 4,5-diaminofluorescein diacetate (DAF-2DA) which is actively diffused into cells, once taken up by cells cytoplasmic esterases cleave the acetate groups to generate 4,5-diaminofluorescein; DAF-2. The generated DAF-2 can readily react with N2O3, which is an oxidation product of NO to generate the highly fluorescent DAF-2T (triazolofluorescein). There are various advantages and disadvantages associated with this method, but to its advantage in diffusion closely to NO producing sites, it is widely used for localization studies. Here, we describe method to make sections of the roots and localization of NO in roots subjected to hypoxic stress.

Angiostrongylus cantonensis daf-2 regulates dauer, longevity and stress in Caenorhabditis elegans.

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Yan, Baolong; Sun, Weiwei; Shi, Xiaomeng; Huang, Liyang; Chen, Lingzi; Wang, Suhua; Yan, Lanzhu; Liang, Shaohui; Huang, Huicong

2017-06-15

The insulin-like signaling (IIS) pathway is considered to be significant in regulating fat metabolism, dauer formation, stress response and longevity in Caenorhabditis elegans. "Dauer hypothesis" indicates that similar IIS transduction mechanism regulates dauer development in free-living nematode C. elegans and the development of infective third-stage larvae (iL3) in parasitic nematodes, and this is bolstered by a few researches on structures and functions of the homologous genes in the IIS pathway cloned from several parasitic nematodes. In this study, we identified the insulin-like receptor encoding gene, Acan-daf-2, from the parasitic nematode Angiostrongylus cantonensis, and determined the genomic structures, transcripts and functions far more thorough in longevity, stress resistance and dauer formation. The sequence of Acan-DAF-2, consisting of 1413 amino acids, contained all of the characteristic domains of insulin-like receptors from other taxa. The expression patterns of Acan-daf-2 in the C. elegans surrogate system showed that pAcan-daf-2:gfp was only expressed in intestine, compared with the orthologue in C. elegans, Ce-daf-2 in both intestine and neurons. In addition to the similar genomic organization to Ce-daf-2, Acan-DAF-2 could also negatively regulate Ce-DAF-16A through nuclear/cytosolic translocation and partially restore the C. elegans daf-2(e1370) mutation in longevity, dauer formation and stress resistance. These findings provided further evidence of the functional conservation of DAF-2 between parasitic nematodes and the free-living nematode C. elegans, and might be significant in understanding the developmental biology of nematode parasites, particularly in the infective process and the host-specificity. Copyright © 2017. Published by Elsevier B.V.

C. elegans DAF-16/FOXO interacts with TGF-ß/BMP signaling to induce germline tumor formation via mTORC1 activation.

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Wenjing Qi

2017-05-01

Full Text Available Activation of the FOXO transcription factor DAF-16 by reduced insulin/IGF signaling (IIS is considered to be beneficial in C. elegans due to its ability to extend lifespan and to enhance stress resistance. In the germline, cell-autonomous DAF-16 activity prevents stem cell proliferation, thus acting tumor-suppressive. In contrast, hypodermal DAF-16 causes a tumorous germline phenotype characterized by hyperproliferation of the germline stem cells and rupture of the adjacent basement membrane. Here we show that cross-talk between DAF-16 and the transforming growth factor ß (TGFß/bone morphogenic protein (BMP signaling pathway causes germline hyperplasia and results in disruption of the basement membrane. In addition to activating MADM/NRBP/hpo-11 gene alone, DAF-16 also directly interacts with both R-SMAD proteins SMA-2 and SMA-3 in the nucleus to regulate the expression of mTORC1 pathway. Knocking-down of BMP genes or each of the four target genes in the hypodermis was sufficient to inhibit germline proliferation, indicating a cell-non-autonomously controlled regulation of stem cell proliferation by somatic tissues. We propose the existence of two antagonistic DAF-16/FOXO functions, a cell-proliferative somatic and an anti-proliferative germline activity. Whereas germline hyperplasia under reduced IIS is inhibited by DAF-16 cell-autonomously, activation of somatic DAF-16 in the presence of active IIS promotes germline proliferation and eventually induces tumor-like germline growth. In summary, our results suggest a novel pathway crosstalk of DAF-16 and TGF-ß/BMP that can modulate mTORC1 at the transcriptional level to cause stem-cell hyperproliferation. Such cell-type specific differences may help explaining why human FOXO activity is considered to be tumor-suppressive in most contexts, but may become oncogenic, e.g. in chronic and acute myeloid leukemia.

C. elegans DAF-16/FOXO interacts with TGF-ß/BMP signaling to induce germline tumor formation via mTORC1 activation.

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Qi, Wenjing; Yan, Yijian; Pfeifer, Dietmar; Donner V Gromoff, Erika; Wang, Yimin; Maier, Wolfgang; Baumeister, Ralf

2017-05-01

Activation of the FOXO transcription factor DAF-16 by reduced insulin/IGF signaling (IIS) is considered to be beneficial in C. elegans due to its ability to extend lifespan and to enhance stress resistance. In the germline, cell-autonomous DAF-16 activity prevents stem cell proliferation, thus acting tumor-suppressive. In contrast, hypodermal DAF-16 causes a tumorous germline phenotype characterized by hyperproliferation of the germline stem cells and rupture of the adjacent basement membrane. Here we show that cross-talk between DAF-16 and the transforming growth factor ß (TGFß)/bone morphogenic protein (BMP) signaling pathway causes germline hyperplasia and results in disruption of the basement membrane. In addition to activating MADM/NRBP/hpo-11 gene alone, DAF-16 also directly interacts with both R-SMAD proteins SMA-2 and SMA-3 in the nucleus to regulate the expression of mTORC1 pathway. Knocking-down of BMP genes or each of the four target genes in the hypodermis was sufficient to inhibit germline proliferation, indicating a cell-non-autonomously controlled regulation of stem cell proliferation by somatic tissues. We propose the existence of two antagonistic DAF-16/FOXO functions, a cell-proliferative somatic and an anti-proliferative germline activity. Whereas germline hyperplasia under reduced IIS is inhibited by DAF-16 cell-autonomously, activation of somatic DAF-16 in the presence of active IIS promotes germline proliferation and eventually induces tumor-like germline growth. In summary, our results suggest a novel pathway crosstalk of DAF-16 and TGF-ß/BMP that can modulate mTORC1 at the transcriptional level to cause stem-cell hyperproliferation. Such cell-type specific differences may help explaining why human FOXO activity is considered to be tumor-suppressive in most contexts, but may become oncogenic, e.g. in chronic and acute myeloid leukemia.

DAF as a therapeutic target for steroid hormones: implications for host-pathogen interactions.

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Nowicki, Bogdan; Nowicki, Stella

2013-01-01

In this chapter, we present a concise historic prospective and a summary of accumulated knowledge on steroid hormones, DAF expression, and therapeutic implication of steroid hormone treatment on multiple pathologies, including infection and the host-pathogen interactions. DAF/CD55 plays multiple physiologic functions including tissue protection from the cytotoxic complement injury, an anti-inflammatory function due to its anti-adherence properties which enhance transmigration of monocytes and macrophages and reduce tissue injury. DAF physiologic functions are essential in many organ systems including pregnancy for protection of the semiallogeneic fetus or for preventing uncontrolled infiltration by white cells in their pro- and/or anti-inflammatory functions. DAF expression appears to have multiple regulatory tissue-specific and/or menstrual cycle-specific mechanisms, which involve complex signaling mechanisms. Regulation of DAF expression may involve a direct or an indirect effect of at least the estrogen, progesterone, and corticosteroid regulatory pathways. DAF is exploited in multiple pathologic conditions by pathogens and viruses in chronic tissue infection processes. The binding of Escherichia coli bearing Dr adhesins to the DAF/CD55 receptor is DAF density dependent and triggers internalization of E. coli via an endocytic pathway involving CD55, lipid rafts, and microtubules. Dr+ E. coli or Dr antigen may persist in vivo in the interstitium for several months. Further understanding of such processes should be instrumental in designing therapeutic strategies for multiple conditions involving DAF's protective or pathologic functions and tailoring host expression of DAF.

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Hc-daf-2 encodes an insulin-like receptor kinase in the barber's pole worm, Haemonchus contortus, and restores partial dauer regulation.

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Li, Facai; Lok, James B; Gasser, Robin B; Korhonen, Pasi K; Sandeman, Mark R; Shi, Deshi; Zhou, Rui; Li, Xiangrui; Zhou, Yanqin; Zhao, Junlong; Hu, Min

2014-06-01

Infective L3s (iL3s) of parasitic nematodes share common behavioural, morphological and developmental characteristics with the developmentally arrested (dauer) larvae of the free-living nematode Caenorhabditis elegans. It is proposed that similar molecular mechanisms regulate entry into or exit from the dauer stage in C. elegans, and the transition from free-living to parasitic forms of parasitic nematodes. In C. elegans, one of the key factors regulating the dauer transition is the insulin-like receptor (designated Ce-DAF-2) encoded by the gene Ce-daf-2. However, nothing is known about DAF-2 homologues in most parasitic nematodes. Here, using a PCR-based approach, we identified and characterised a gene (Hc-daf-2) and its inferred product (Hc-DAF-2) in Haemonchus contortus (a socioeconomically important parasitic nematode of ruminants). The sequence of Hc-DAF-2 displays significant sequence homology to insulin receptors (IR) in both vertebrates and invertebrates, and contains conserved structural domains. A sequence encoding an important proteolytic motif (RKRR) identified in the predicted peptide sequence of Hc-DAF-2 is consistent with that of the human IR, suggesting that it is involved in the formation of the IR complex. The Hc-daf-2 gene was transcribed in all life stages of H. contortus, with a significant up-regulation in the iL3 compared with other stages. To compare patterns of expression between Hc-daf-2 and Ce-daf-2, reporter constructs fusing the Ce-daf-2 or Hc-daf-2 promoter to sequence encoding GFP were microinjected into the N2 strain of C. elegans, and transgenic lines were established and examined. Both genes showed similar patterns of expression in amphidial (head) neurons, which relate to sensation and signal transduction. Further study by heterologous genetic complementation in a daf-2-deficient strain of C. elegans (CB1370) showed partial rescue of function by Hc-daf-2. Taken together, these findings provide a first insight into the roles of Hc-daf

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Lifescience Database Archive (English)

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Dominant negative mutations of Caenorhabditis elegans daf-7 confer a novel developmental phenotype.

Science.gov (United States)

Crook, Matt; Grant, Warwick N

2013-06-01

TGF-β signaling pathways are involved in the control of development in every member of the animal kingdom. As such, TGF-β ligands are widely divergent yet retain a set of core conserved features, specifically, a pre-protein cleavage site and several conserved ligand domain residues, the disruption of which produces a dominant negative phenotype. We have extended these observations into an invertebrate system by creating a series of loss-of-function Caenorhabditis elegans daf-7 transgenes. When we tested these mutant transgenes in a daf-7/+ background, we saw a molting and excretory canal phenotype. Members of both pathways downstream of daf-4 were required for this phenotype. Our results show that the basic mechanisms of TGF-β function are conserved across the animal kingdom. A subset of our daf-7 mutations also produced an unexpected and novel phenotype. Epistasis experiments demonstrated that both daf-3/-5 and sma-4/-9 were downstream of our mutant daf-7 transgenes, which suggests not only a role for DAF-7 in the control of molting and the development of the excretory system but also that daf-7 and dbl-1 signaling may converge downstream of their shared Type II receptor, daf-4. Our approach may unveil new roles in development for other invertebrate TGF-β ligands. Copyright © 2013 Wiley Periodicals, Inc.

Activation of DAF-16/FOXO by reactive oxygen species contributes to longevity in long-lived mitochondrial mutants in Caenorhabditis elegans.

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Senchuk, Megan M; Dues, Dylan J; Schaar, Claire E; Johnson, Benjamin K; Madaj, Zachary B; Bowman, Megan J; Winn, Mary E; Van Raamsdonk, Jeremy M

2018-03-01

Mild deficits in mitochondrial function have been shown to increase lifespan in multiple species including worms, flies and mice. Here, we study three C. elegans mitochondrial mutants (clk-1, isp-1 and nuo-6) to identify overlapping genetic pathways that contribute to their longevity. We find that genes regulated by the FOXO transcription factor DAF-16 are upregulated in all three strains, and that the transcriptional changes present in these worms overlap significantly with the long-lived insulin-IGF1 signaling pathway mutant daf-2. We show that DAF-16 and multiple DAF-16 interacting proteins (MATH-33, IMB-2, CST-1/2, BAR-1) are required for the full longevity of all three mitochondrial mutants. Our results suggest that the activation of DAF-16 in these mutants results from elevated levels of reactive oxygen species. Overall, this work reveals an overlapping genetic pathway required for longevity in three mitochondrial mutants, and, combined with previous work, demonstrates that DAF-16 is a downstream mediator of lifespan extension in multiple pathways of longevity.

Partial characterization of the cross-reacting determinant, a carbohydrate epitope shared by decay accelerating factor and the variant surface glycoprotein of the African Trypanosoma brucei.

Science.gov (United States)

Shak, S; Davitz, M A; Wolinsky, M L; Nussenzweig, V; Turner, M J; Gurnett, A

1988-03-15

The variant surface glycoprotein (VSG) of the African trypanosome is anchored in the cell membrane by a complex glycan attached to phosphatidylinositol. The carboxyl terminal portion of VSG contains a cryptic carbohydrate epitope, the cross-reacting determinant (CRD), that is revealed only after removal of the diacylglycerol by phosphatidylinositol-specific phospholipase C (PIPLC) or VSG lipase. Recently, we have shown that after hydrolysis by PIPLC, decay-accelerating factor (DAF)--a mammalian phosphatidylinositol-anchored protein--also contains the CRD epitope. Using a two site immunoradiometric assay in which the capturing antibody is a monoclonal antibody to DAF and the revealing antibody is anti-CRD, we now show that sugar phosphates significantly inhibited the binding of anti-CRD antibody to DAF released by PIPLC. DL-myo-inositol 1,2-cyclic phosphate was the most potent inhibitor of binding (IC50 less than 10(-8) M). Other sugar phosphates, such as alpha-D-glucose-1-phosphate, which also possess adjacent hydroxyl and phosphate moieties in cis also inhibited binding at low concentrations (IC50 = 10(-5) to 10(-4) M). In contrast, sugar phosphates which do not possess adjacent hydroxyl and phosphate moieties in cis and simple sugars weakly inhibited binding (IC50 greater than 10(-3) M). These results suggest that myo-inositol 1,2-cyclic phosphate contributes significantly to the epitope recognized by the anti-CRD antibody and is consistent with analysis of the carboxyl terminus of VSG, which also suggested the presence of the cyclic inositol phosphate. In light of the recent findings that human serum contains a glycan-phosphatidyl-inositol-specific phospholipase D, which converts DAF from a hydrophobic to a hydrophilic form lacking the CRD, the observation that the phosphate is crucial for expression of the epitope may be relevant in understanding the origin of CRD-negative DAF in urine and plasma.

File list: Oth.ALL.20.daf-12.AllCell [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Oth.ALL.20.daf-12.AllCell ce10 TFs and others daf-12 All cell types SRX146513,SRX14...6512,SRX065713,SRX065705,SRX065706,SRX065714 http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/assembled/Oth.ALL.20.daf-12.AllCell.bed ...

File list: Oth.ALL.50.daf-12.AllCell [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Oth.ALL.50.daf-12.AllCell ce10 TFs and others daf-12 All cell types SRX065714,SRX06...5713,SRX146512,SRX065705,SRX146513,SRX065706 http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/assembled/Oth.ALL.50.daf-12.AllCell.bed ...

File list: Oth.ALL.05.daf-12.AllCell [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Oth.ALL.05.daf-12.AllCell ce10 TFs and others daf-12 All cell types SRX146513,SRX06...5705,SRX146512,SRX065706,SRX065713,SRX065714 http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/assembled/Oth.ALL.05.daf-12.AllCell.bed ...

File list: Oth.ALL.10.daf-12.AllCell [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Oth.ALL.10.daf-12.AllCell ce10 TFs and others daf-12 All cell types SRX146513,SRX06...5706,SRX065705,SRX146512,SRX065713,SRX065714 http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/assembled/Oth.ALL.10.daf-12.AllCell.bed ...

Dansk Almenmedicinsk Forskningsdag - DAF 2015

DEFF Research Database (Denmark)

Geyti, Christine Ladegaard

2015-01-01

Den 18. marts blev Dansk Almenmedicinsk Forskningsdag (DAF) afholdt i København. Arrangementet foregik i Domus Medicas flotte adelspalæ med prægtige lysekroner og hyggelige opholdsrum med bløde lænestole og gamle bøger op og ned ad væggene. Der blev nu ikke megen tid til at slænge sig, for progra......Den 18. marts blev Dansk Almenmedicinsk Forskningsdag (DAF) afholdt i København. Arrangementet foregik i Domus Medicas flotte adelspalæ med prægtige lysekroner og hyggelige opholdsrum med bløde lænestole og gamle bøger op og ned ad væggene. Der blev nu ikke megen tid til at slænge sig...

Regulation of Caenorhabditis elegans vitellogenesis by DAF-2/IIS through separable transcriptional and posttranscriptional mechanisms.

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DePina, Ana S; Iser, Wendy B; Park, Sung-Soo; Maudsley, Stuart; Wilson, Mark A; Wolkow, Catherine A

2011-07-12

Evolutionary theories of aging propose that longevity evolves as a competition between reproduction and somatic maintenance for a finite pool of resources. Reproduction is thought to shorten lifespan by depleting resources from processes promoting somatic maintenance. Maternal yolk production, vitellogenesis, represents a significant maternal cost for reproduction and is suppressed under genetic and environmental conditions that extend lifespan. However, little is known about the pathways regulating vitellogenesis in response to prolongevity cues. In order to identify mechanisms that suppress vitellogenesis under prolongevity conditions, we studied factors regulating vitellogenesis in C. elegans nematodes. In C. elegans, vitellogenesis is depressed in the absence of insulin-like signaling (IIS). We found that the C. elegans daf-2/IIS pathway regulates vitellogenesis through two mechanisms. vit-2 transcript levels in daf-2 mutants were indirectly regulated through a germline-dependent signal, and could be rescued by introduction of daf-2(+) sperm. However, yolk protein (YP) levels in daf-2 mutants were also regulated by germline-independent posttranscriptional mechanisms. C. elegans vitellogenesis is regulated transcriptionally and posttranscriptionally in response to environmental and reproductive cues. The daf-2 pathway suppressed vitellogenesis through transcriptional mechanisms reflecting reproductive phenotypes, as well as distinct posttranscriptional mechanisms. This study reveals that pleiotropic effects of IIS pathway mutations can converge on a common downstream target, vitellogenesis, as a mechanism to modulate longevity.

Regulation of Caenorhabditis elegans vitellogenesis by DAF-2/IIS through separable transcriptional and posttranscriptional mechanisms

Directory of Open Access Journals (Sweden)

Wilson Mark A

2011-07-01

Full Text Available Abstract Background Evolutionary theories of aging propose that longevity evolves as a competition between reproduction and somatic maintenance for a finite pool of resources. Reproduction is thought to shorten lifespan by depleting resources from processes promoting somatic maintenance. Maternal yolk production, vitellogenesis, represents a significant maternal cost for reproduction and is suppressed under genetic and environmental conditions that extend lifespan. However, little is known about the pathways regulating vitellogenesis in response to prolongevity cues. Results In order to identify mechanisms that suppress vitellogenesis under prolongevity conditions, we studied factors regulating vitellogenesis in C. elegans nematodes. In C. elegans, vitellogenesis is depressed in the absence of insulin-like signaling (IIS. We found that the C. elegans daf-2/IIS pathway regulates vitellogenesis through two mechanisms. vit-2 transcript levels in daf-2 mutants were indirectly regulated through a germline-dependent signal, and could be rescued by introduction of daf-2(+ sperm. However, yolk protein (YP levels in daf-2 mutants were also regulated by germline-independent posttranscriptional mechanisms. Conclusions C. elegans vitellogenesis is regulated transcriptionally and posttranscriptionally in response to environmental and reproductive cues. The daf-2 pathway suppressed vitellogenesis through transcriptional mechanisms reflecting reproductive phenotypes, as well as distinct posttranscriptional mechanisms. This study reveals that pleiotropic effects of IIS pathway mutations can converge on a common downstream target, vitellogenesis, as a mechanism to modulate longevity.

A 44 bp intestine-specific hermaphrodite-specific enhancer from the C. elegans vit-2 vitellogenin gene is directly regulated by ELT-2, MAB-3, FKH-9 and DAF-16 and indirectly regulated by the germline, by daf-2/insulin signaling and by the TGF-β/Sma/Mab pathway.

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Goszczynski, Barbara; Captan, Vasile V; Danielson, Alicia M; Lancaster, Brett R; McGhee, James D

2016-05-01

The Caenorhabditis elegans vitellogenin genes are transcribed in the intestine of adult hermaphrodites but not of males. A 44-bp region from the vit-2 gene promoter is able largely to reconstitute this tissue-, stage- and sex-specific-expression. This "enhancer" contains a binding site for the DM-domain factor MAB-3, the male-specific repressor of vitellogenesis, as well as an activator site that we show is the direct target of the intestinal GATA factor ELT-2. We further show that the enhancer is directly activated by the winged-helix/forkhead-factor FKH-9, (whose gene has been shown by others to be a direct target of DAF-16), by an unknown activator binding to the MAB-3 site, and by the full C. elegans TGF-β/Sma/Mab pathway acting within the intestine. The vit-2 gene has been shown by others to be repressed by the daf-2/daf-16 insulin signaling pathway, which so strongly influences aging and longevity in C. elegans. We show that the activity of the 44 bp vit-2 enhancer is abolished by loss of daf-2 but is restored by simultaneous loss of daf-16. DAF-2 acts from outside of the intestine but DAF-16 acts both from outside of the intestine and from within the intestine where it binds directly to the same non-canonical target site that interacts with FKH-9. Activity of the 44 bp vit-2 enhancer is also inhibited by loss of the germline, in a manner that is only weakly influenced by DAF-16 but that is strongly influenced by KRI-1, a key downstream effector in the pathway by which germline loss increases C. elegans lifespan. The complex behavior of this enhancer presumably allows vitellogenin gene transcription to adjust to demands of body size, germline proliferation and nutritional state but we suggest that the apparent involvement of this enhancer in aging and longevity "pathways" could be incidental. Copyright © 2016 Elsevier Inc. All rights reserved.

Study of local structure by DAFS

International Nuclear Information System (INIS)

Mizuki, Jun-ichiro

1997-01-01

We will describe a rather new X-ray structural technique, Diffraction Anomalous Fine Structure (DAFS), in which the Bragg diffraction intensities of a fixed momentum transfer is measured as a function of the incident X-ray energy. This technique can provide the same short-range structural information as XAFS. Because DAFS combines the capabilities of diffraction and XAFS into a single technique, it has two enhanced sensitivities compared to the separate technique. These are 'spatial selectivity' and 'site selectivity'. In this chapter semiconductor interface structure study as an example for spatial selectivity and structural study of high Tc superconductor as an example for site selectivity will be shown. (author)

A splice acceptor mutation in C. elegans daf-19/Rfx disrupts functional specialization of male-specific ciliated neurons but does not affect ciliogenesis.

Science.gov (United States)

Wells, Kristen L; Rowneki, Mazhgan; Killian, Darrell J

2015-04-01

RFX transcription factors are master regulators of ciliogenesis in diverse animal species. The sole Caenorhabditis elegans RFX homolog, DAF-19, plays at least two roles in the formation of functional cilia. The DAF-19(C) isoform is required for ciliogenesis and the DAF-19(M) isoform is required for the functional specialization of a subset of male-specific ciliated neurons called PKD neurons. Here we report the identification of a novel mutation, daf-19(sm129), which disrupts the functional specification of PKD neurons and thus suggests that daf-19m activity is compromised. However, ciliogenesis is not disrupted in daf-19(sm129) mutants suggesting that daf-19c activity is retained. The sm129 mutation disrupts a splice acceptor site adjacent to an exon common to the daf-19c and daf-19m isoforms resulting in aberrant splicing in a proportion of transcripts. While aberrant splicing of daf-19c to upstream cryptic sites results in in-frame and functional products, a large proportion of daf-19m mRNAs include the entire upstream intron, which introduces a frameshift and stop codons. At least 15% of disease-causing mutations affect splicing of the gene bearing the mutation, thus it is important to understand the consequences of splice site mutations on gene function. However, predicting the effects of a splice site mutation remains difficult and experimental determination is still required. Using daf-19(sm129) as a model, our results suggest that this problem is exacerbated when a splice acceptor mutation is used by multiple isoforms of the same gene because the effects on each isoform can be dramatically different. Copyright © 2015 Elsevier B.V. All rights reserved.

Lowbush cranberry acts through DAF-16/FOXO signaling to promote increased lifespan and axon branching in aging posterior touch receptor neurons.

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Scerbak, Courtney; Vayndorf, Elena; Hernandez, Alicia; McGill, Colin; Taylor, Barbara

2018-05-01

Medicinal berries are appreciated for their health benefits, in traditional ecological knowledge and nutrition science. Determining the cellular mechanisms underlying the effects of berry supplementation may contribute to our understanding of aging. Here, we report that lowbush cranberry (Vaccinium vitis-idaea) treatment causes marked nuclear localization of the central aging-related transcription factor DAF-16/FOXO in aged Caenorhabditis elegans. Further, functional DAF-16 is required for the lifespan extension, improved mechanosensation, and posterior touch receptor neuron morphological changes induced by lowbush cranberry treatments. DAF-16 is not observed in nuceli nor required for lifespan extension in lifespan-extending Alaskan blueberry treatments and, while DAF-16 is not visibly induced into the nucleus in lifespan-extending Alaskan chaga treatments, it is required for chaga-induced lifespan extension. These findings underscore the importance of DAF-16 in the aging of whole organisms and touch receptor neurons and also, importantly, indicate that this critical pathway is not always activated upon consumption of functional foods that impact aging.

Application of the pothole DAF method to vehicles traversing periodic roadway irregularities

Science.gov (United States)

Pesterev, A. V.; Bergman, L. A.; Tan, C. A.; Yang, B.

2005-01-01

This paper is a sequel to the work discussed in Pesterev et al. (Journal of Sound and Vibration, in press). In that paper, it was suggested that the technique to determine the effect of a local road surface irregularity on the dynamics of a vehicle modelled as a linear multi-degree-of-freedom system relies on the so-called pothole dynamic amplification factor (DAF), which is a complex-valued function specific to the irregularity shape. This paper discusses the companion problem of how to determine the DAF function for an irregularity represented as a superposition of simpler ones. Another purpose of this paper is to demonstrate the application of the pothole DAF functions technique to finding a priori estimates of the effect of irregularities with a repeated structure. Specifically, we solve the problem of finding the conditions under which the dynamic effect of two identical potholes located one after another is greater than that due to the single pothole. We also find the estimate for the number of periods of a periodic irregularity that are sufficient in order to consider the oscillator response as steady state. The discussions are illustrated by numerical examples.

Identification of ligands for DAF-12 that govern dauer formation and reproduction in C. elegans.

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Motola, Daniel L; Cummins, Carolyn L; Rottiers, Veerle; Sharma, Kamalesh K; Li, Tingting; Li, Yong; Suino-Powell, Kelly; Xu, H Eric; Auchus, Richard J; Antebi, Adam; Mangelsdorf, David J

2006-03-24

In response to environmental and dietary cues, the C. elegans orphan nuclear receptor, DAF-12, regulates dauer diapause, reproductive development, fat metabolism, and life span. Despite strong evidence for hormonal control, the identification of the DAF-12 ligand has remained elusive. In this work, we identified two distinct 3-keto-cholestenoic acid metabolites of DAF-9, a cytochrome P450 involved in hormone production, that function as ligands for DAF-12. At nanomolar concentrations, these steroidal ligands (called dafachronic acids) bind and transactivate DAF-12 and rescue the hormone deficiency of daf-9 mutants. Interestingly, DAF-9 has a biochemical activity similar to mammalian CYP27A1 catalyzing addition of a terminal acid to the side chain of sterol metabolites. Together, these results define the first steroid hormones in nematodes as ligands for an invertebrate orphan nuclear receptor and demonstrate that steroidal regulation of reproduction, from biology to molecular mechanism, is conserved from worms to humans.

PMK-1 p38 MAPK promotes cadmium stress resistance, the expression of SKN-1/Nrf and DAF-16 target genes, and protein biosynthesis in Caenorhabditis elegans.

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Keshet, Alex; Mertenskötter, Ansgar; Winter, Sarah A; Brinkmann, Vanessa; Dölling, Ramona; Paul, Rüdiger J

2017-12-01

The mechanisms of cadmium (Cd) resistance are complex and not sufficiently understood. The present study, therefore, aimed at assessing the roles of important components of stress-signaling pathways and of ABC transporters under severe Cd stress in Caenorhabditis elegans. Survival assays on mutant and control animals revealed a significant promotion of Cd resistance by the PMK-1 p38 MAP kinase, the transcription factor DAF-16/FoxO, and the ABC transporter MRP-1. Transcriptome profiling by RNA-Seq on wild type and a pmk-1 mutant under control and Cd stress conditions revealed, inter alia, a PMK-1-dependent promotion of gene expression for the translational machinery. PMK-1 also promoted the expression of target genes of the transcription factors SKN-1/Nrf and DAF-16 in Cd-stressed animals, which included genes for molecular chaperones or immune proteins. Gene expression studies by qRT-PCR confirmed the positive effects of PMK-1 on DAF-16 activity under Cd stress and revealed negative effects of DAF-16 on the expression of genes for MRP-1 and DAF-15/raptor. Additional studies on pmk-1 RNAi-treated wild type and mutant strains provided further information on the effects of PMK-1 on SKN-1 and DAF-16, which resulted in a model of these relationships. The results of this study demonstrate a central role of PMK-1 for the processing of cellular responses to abiotic and biotic stressors, with the promoting effects of PMK-1 on Cd resistance mostly mediated by the transcription factors SKN-1 and DAF-16.

Piceatannol extends the lifespan of Caenorhabditis elegans via DAF-16.

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Shen, Peiyi; Yue, Yiren; Sun, Quancai; Kasireddy, Nandita; Kim, Kee-Hong; Park, Yeonhwa

2017-05-06

Piceatannol is a natural stilbene with many beneficial effects, such as antioxidative, anti-inflammatory, antiatherogenic activities; however, its role on aging is not known. In this study, we used Caenorhabditis elegans as an animal model to study the effect of piceatannol on its lifespan and investigated the underlying mechanisms. The results showed that 50 and 100 µM piceatannol significantly extended the lifespan of C. elegans without altering the growth rate, worm size and progeny production. Piceatannol delayed the age-related decline of pumping rate and locomotive activity, and protected the worms from heat and oxidative stress. This study further indicated that lifespan extension and enhanced stress resistance induced by piceatannol requires DAF-16. Since DAF-16 is conserved from nematodes to mammals, our study may have important implications in utilizing piceatannol to promote healthy aging and combat age-related disease in humans. © 2016 BioFactors, 43(3):379-387, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

RNA surveillance via nonsense-mediated mRNA decay is crucial for longevity in daf-2/insulin/IGF-1 mutant C. elegans.

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Son, Heehwa G; Seo, Mihwa; Ham, Seokjin; Hwang, Wooseon; Lee, Dongyeop; An, Seon Woo A; Artan, Murat; Seo, Keunhee; Kaletsky, Rachel; Arey, Rachel N; Ryu, Youngjae; Ha, Chang Man; Kim, Yoon Ki; Murphy, Coleen T; Roh, Tae-Young; Nam, Hong Gil; Lee, Seung-Jae V

2017-03-09

Long-lived organisms often feature more stringent protein and DNA quality control. However, whether RNA quality control mechanisms, such as nonsense-mediated mRNA decay (NMD), which degrades both abnormal as well as some normal transcripts, have a role in organismal aging remains unexplored. Here we show that NMD mediates longevity in C. elegans strains with mutations in daf-2/insulin/insulin-like growth factor 1 receptor. We find that daf-2 mutants display enhanced NMD activity and reduced levels of potentially aberrant transcripts. NMD components, including smg-2/UPF1, are required to achieve the longevity of several long-lived mutants, including daf-2 mutant worms. NMD in the nervous system of the animals is particularly important for RNA quality control to promote longevity. Furthermore, we find that downregulation of yars-2/tyrosyl-tRNA synthetase, an NMD target transcript, by daf-2 mutations contributes to longevity. We propose that NMD-mediated RNA surveillance is a crucial quality control process that contributes to longevity conferred by daf-2 mutations.

Structural and functional characterization of a novel gene, Hc-daf-22, from the strongylid nematode Haemonchus contortus.

Science.gov (United States)

Guo, Xiaolu; Zhang, Hongli; Zheng, Xiuping; Zhou, Qianjin; Yang, Yi; Chen, Xueqiu; Du, Aifang

2016-07-29

The strongylid nematode Haemonchus contortus is a parasite of major concern for modern livestock husbandry because hostile environmental conditions may induce diapause in the early fourth-stage larvae. A new gene Hc-daf-22 was identified which is the homologue of Ce-daf-22 and human SCPx. Genome walking and RACE were performed to obtain the whole cDNA and genomic sequence of this gene. Using qRT-PCR with all developmental stages as templates to explore the transcription level and micro-injection was applied to confirm the promoter activity of the 5'-flanking region. Overexpression, rescue and RNA interference experiments were performed in N2, daf-22 mutant (ok 693) strains of C. elegans to study the gene function of Hc-daf-22. The full length gene of Hc-daf-22 (6,939 bp) contained 16 exons separated by 15 introns, and encoded a cDNA of 1,602 bp (533 amino acids, estimated at about 59.3 kDa) with a peak in L3 and L4 in transcriptional level. The Hc-DAF-22 protein was consisted of a 3-oxoacyl-CoA thiolase domain and a SCP2 domain and evolutionarily conserved. The 1,548 bp fragment upstream of the 5'-flanking region was confirmed to have promoter activity compared with 5'-flanking region of Ce-daf-22. The rescue experiment by micro-injection of daf-22 (ok693) mutant strain showed significant increase in body size and brood size in the rescued worms with significantly reduced or completely absent fat granules confirmed by Oil red O staining, indicating that Hc-daf-22 could partially rescue the function of Ce-daf-22. Furthermore, RNAi with Hc-daf-22 could partially silence the endogenous Ce-daf-22 in N2 worms and mimic the phenotype of daf-22 (ok693) mutants. The gene Hc-daf-22 was isolated and its function identified using C. elegans as a model organism. Our results indicate that Hc-daf-22 shared similar characteristics and function with Ce-daf-22 and may play an important role in peroxisomal β-oxidation and the development in H. contortus.

Germline signaling mediates the synergistically prolonged longevity produced by double mutations in daf-2 and rsks-1 in C. elegans.

Science.gov (United States)

Chen, Di; Li, Patrick Wai-Lun; Goldstein, Benjamin A; Cai, Waijiao; Thomas, Emma Lynn; Chen, Fen; Hubbard, Alan E; Melov, Simon; Kapahi, Pankaj

2013-12-26

Inhibition of DAF-2 (insulin-like growth factor 1 [IGF-1] receptor) or RSKS-1 (S6K), key molecules in the insulin/IGF-1 signaling (IIS) and target of rapamycin (TOR) pathways, respectively, extend lifespan in Caenorhabditis elegans. However, it has not been clear how and in which tissues they interact with each other to modulate longevity. Here, we demonstrate that a combination of mutations in daf-2 and rsks-1 produces a nearly 5-fold increase in longevity that is much greater than the sum of single mutations. This synergistic lifespan extension requires positive feedback regulation of DAF-16 (FOXO) via the AMP-activated protein kinase (AMPK) complex. Furthermore, we identify germline as the key tissue for this synergistic longevity. Moreover, germline-specific inhibition of rsks-1 activates DAF-16 in the intestine. Together, our findings highlight the importance of the germline in the significantly increased longevity produced by daf-2 rsks-1, which has important implications for interactions between the two major conserved longevity pathways in more complex organisms. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Localization of a guanylyl cyclase to chemosensory cilia requires the novel ciliary MYND domain protein DAF-25.

Directory of Open Access Journals (Sweden)

Victor L Jensen

2010-11-01

Full Text Available In harsh conditions, Caenorhabditis elegans arrests development to enter a non-aging, resistant diapause state called the dauer larva. Olfactory sensation modulates the TGF-β and insulin signaling pathways to control this developmental decision. Four mutant alleles of daf-25 (abnormal DAuer Formation were isolated from screens for mutants exhibiting constitutive dauer formation and found to be defective in olfaction. The daf-25 dauer phenotype is suppressed by daf-10/IFT122 mutations (which disrupt ciliogenesis, but not by daf-6/PTCHD3 mutations (which prevent environmental exposure of sensory cilia, implying that DAF-25 functions in the cilia themselves. daf-25 encodes the C. elegans ortholog of mammalian Ankmy2, a MYND domain protein of unknown function. Disruption of DAF-25, which localizes to sensory cilia, produces no apparent cilia structure anomalies, as determined by light and electron microscopy. Hinting at its potential function, the dauer phenotype, epistatic order, and expression profile of daf-25 are similar to daf-11, which encodes a cilium-localized guanylyl cyclase. Indeed, we demonstrate that DAF-25 is required for proper DAF-11 ciliary localization. Furthermore, the functional interaction is evolutionarily conserved, as mouse Ankmy2 interacts with guanylyl cyclase GC1 from ciliary photoreceptors. The interaction may be specific because daf-25 mutants have normally-localized OSM-9/TRPV4, TAX-4/CNGA1, CHE-2/IFT80, CHE-11/IFT140, CHE-13/IFT57, BBS-8, OSM-5/IFT88, and XBX-1/D2LIC in the cilia. Intraflagellar transport (IFT (required to build cilia is not defective in daf-25 mutants, although the ciliary localization of DAF-25 itself is influenced in che-11 mutants, which are defective in retrograde IFT. In summary, we have discovered a novel ciliary protein that plays an important role in cGMP signaling by localizing a guanylyl cyclase to the sensory organelle.

Role of DAF-21protein in Caenorhabditis elegans immunity against Proteus mirabilis infection.

Science.gov (United States)

JebaMercy, Gnanasekaran; Durai, Sellegounder; Prithika, Udayakumar; Marudhupandiyan, Shanmugam; Dasauni, Pushpanjali; Kundu, Suman; Balamurugan, Krishnaswamy

2016-08-11

Caenorhabditis elegans is emerging as one of the handy model for proteome related studies due to its simplest system biology. The present study, deals with changes in protein expression in C. elegans infected with Proteus mirabilis. Proteins were separated using two-dimensional differential gel electrophoresis (2D-DIGE) and identified using MALDI-TOF. Twelve distinctly regulated proteins identified in the infected worms, included heat shock proteins involved stress pathway (HSP-1 and HSP-6), proteins involved in immune response pathway (DAF-21), enzymes involved in normal cellular process (Eukaryotic translation Elongation Factor, actin family member, S-adenosyl homocysteine hydrolase ortholog, glutamate dehydrogenase and Vacuolar H ATPase family member) and few least characterized proteins (H28O16.1 and H08J11.2). The regulation of selected players at the transcriptional level during Proteus mirabilis infection was analyzed using qPCR. Physiological experiments revealed the ability of P. mirabilis to kill daf-21 mutant C. elegans significantly compared with the wild type. This is the first report studying proteome changes in C. elegans and exploring the involvement of MAP Kinase pathway during P. mirabilis infection. This is the first report studying proteome changes in C. elegans during P. mirabilis infection. The present study explores the role and contribution of MAP Kinase pathway and its regulator protein DAF-21 involvement in the immunity against opportunistic pathogen P. mirabilis infection. Manipulation of this DAF-21 protein in host, may pave the way for new drug development or disease control strategy during opportunistic pathogen infections. Copyright © 2016 Elsevier B.V. All rights reserved.

Cholesterol regulates DAF-16 nuclear localization and fasting-induced longevity in C. elegans.

Science.gov (United States)

Ihara, Akiko; Uno, Masaharu; Miyatake, Koichi; Honjoh, Sakiko; Nishida, Eisuke

2017-01-01

Cholesterol has attracted significant attention as a possible lifespan regulator. It has been reported that serum cholesterol levels have an impact on mortality due to age-related disorders such as cardiovascular disease. Diet is also known to be an important lifespan regulator. Dietary restriction retards the onset of age-related diseases and extends lifespan in various organisms. Although cholesterol and dietary restriction are known to be lifespan regulators, it remains to be established whether cholesterol is involved in dietary restriction-induced longevity. Here, we show that cholesterol deprivation suppresses longevity induced by intermittent fasting, which is one of the dietary restriction regimens that effectively extend lifespan. We also found that cholesterol is required for the fasting-induced upregulation of transcriptional target genes such as the insulin/IGF-1 pathway effector DAF-16 and that cholesterol deprivation suppresses the long lifespan of the insulin/IGF-1 receptor daf-2 mutant. Remarkably, we found that cholesterol plays an important role in the fasting-induced nuclear accumulation of DAF-16. Moreover, knockdown of the cholesterol-binding protein NSBP-1, which has been shown to bind to DAF-16 in a cholesterol-dependent manner and to regulate DAF-16 activity, suppresses both fasting-induced longevity and DAF-16 nuclear accumulation. Furthermore, this suppression was not additive to the cholesterol deprivation-induced suppression, which suggests that NSBP-1 mediates, at least in part, the action of cholesterol to promote fasting-induced longevity and DAF-16 nuclear accumulation. These findings identify a novel role for cholesterol in the regulation of lifespan. Copyright © 2016 Elsevier Inc. All rights reserved.

DhHP-6 extends lifespan of Caenorhabditis elegans by enhancing nuclear translocation and transcriptional activity of DAF-16.

Science.gov (United States)

Huang, Lei; Li, Pengfei; Wang, Guan; Guan, Shuwen; Sun, Xiaoli; Wang, Liping

2013-04-01

Earlier studies have demonstrated that Deuterohaemin-AlaHisThrValGluLys (DhHP-6), a novel porphyrin-peptide, increases lifespan and enhances stress resistance of Caenorhabditis elegans. To explore the possible mechanisms, in this study we investigated the roles of SIR-2.1 and DAF-16 in DhHP-6's function using wild-type and various other mutant strains of C. elegans. DhHP-6's effect was dependent upon DAF-16, and it did not extend the lifespan of the loss-of-function daf-16 mutant strain (daf-16(mu86) I). DhHP-6 enhanced DAF-16 translocation from cytoplasm to nuclei; and it increased DAF-16's transcriptional activity, likely by activating the SIR-2.1/DAF-16 complex. DhHP-6's effect was also dependent upon SIR-2.1, and it did not increase the lifespan of the worms with SIR-2.1 deacetylase activity inhibited by niacin amide (SIR-2.1 inhibitor) and SIR-2.1 RNA interference (RNAi). Niacin amide and RNAi increased DAF-16's nuclear localization; but they decreased DAF-16's transcriptional activity, likely by preventing the formation of the SIR-2.1/DAF-16 complex. These results suggest that DhHP-6 extends the lifespan of C. elegans via SIR 2.1 and DAF-16, and they provide new insights into the molecular mechanisms of aging.

The Deubiquitylase MATH-33 Controls DAF-16 Stability and Function in Metabolism and Longevity

NARCIS (Netherlands)

Heimbucher, Thomas; Liu, Zheng; Bossard, Carine; McCloskey, Richard; Carrano, Andrea C.; Riedel, Christian G.; Tanasa, Bogdan; Klammt, Christian; Fonslow, Bryan R.; Riera, Celine E.; Lillemeier, Bjorn F.; Kemphues, Kenneth; Yates, John R.; O'Shea, Clodagh; Hunter, Tony; Dillin, Andrew

2015-01-01

FOXO family transcription factors are downstream effectors of Insulin/IGF-1 signaling (IIS) and major determinants of aging in organisms ranging from worms to man. The molecular mechanisms that actively promote DAF16/FOXO stability and function are unknown. Here we identify the deubiquitylating

Dansk Almenmedicinsk Forskningsdag - DAF 2013

DEFF Research Database (Denmark)

Jensen, Jacob Reinholdt; Ryborg, Christina Trankjær; Smidth, Margrethe

2013-01-01

Ideen om DAF udsprang på en indisk restaurant for to år siden, da repræsentanter fra det daværende Forskningsudvalg var til Society for Academic Primary Care (SAPC) i Bristol. En konference, hvor den nyeste forskning og de hotteste forskere inden for almen medicin i Storbritannien var repræsenteret...

DAF-16-dependent suppression of immunity during reproduction in Caenorhabditis elegans.

Science.gov (United States)

Miyata, Sachiko; Begun, Jakob; Troemel, Emily R; Ausubel, Frederick M

2008-02-01

To further understand how the nematode Caenorhabditis elegans defends itself against pathogen attack, we analyzed enhanced pathogen resistance (epr) mutants obtained from a forward genetic screen. We also examined several well-characterized sterile mutants that exhibit an Epr phenotype. We found that sterility and pathogen resistance are highly correlated and that resistance in both epr and sterile mutants is dependent on DAF-16 activity. Our data indicate that a DAF-16-dependent signaling pathway distinct from previously described pathways is involved in the activation of genes that confer resistance to bacterial pathogens. The timing of DAF-16-dependent gene activation in sterile mutants coincides with the onset of embryonic development in wild-type animals, suggesting that signals from developing embryos normally downregulate the immune response.

Linking the environment, DAF-7/TGFβ signaling and LAG-2/DSL ligand expression in the germline stem cell niche.

Science.gov (United States)

Pekar, Olga; Ow, Maria C; Hui, Kailyn Y; Noyes, Marcus B; Hall, Sarah E; Hubbard, E Jane Albert

2017-08-15

The developmental accumulation of proliferative germ cells in the C. elegans hermaphrodite is sensitive to the organismal environment. Previously, we found that the TGFβ signaling pathway links the environment and proliferative germ cell accumulation. Neuronal DAF-7/TGFβ causes a DAF-1/TGFβR signaling cascade in the gonadal distal tip cell (DTC), the germline stem cell niche, where it negatively regulates a DAF-3 SMAD and DAF-5 Sno-Ski. LAG-2, a founding DSL ligand family member, is produced in the DTC and activates the GLP-1/Notch receptor on adjacent germ cells to maintain germline stem cell fate. Here, we show that DAF-7/TGFβ signaling promotes expression of lag-2 in the DTC in a daf-3- dependent manner. Using ChIP and one-hybrid assays, we find evidence for direct interaction between DAF-3 and the lag-2 promoter. We further identify a 25 bp DAF-3 binding element required for the DTC lag-2 reporter response to the environment and to DAF-7/TGFβ signaling. Our results implicate DAF-3 repressor complex activity as a key molecular mechanism whereby the environment influences DSL ligand expression in the niche to modulate developmental expansion of the germline stem cell pool. © 2017. Published by The Company of Biologists Ltd.

ASM-3 acid sphingomyelinase functions as a positive regulator of the DAF-2/AGE-1 signaling pathway and serves as a novel anti-aging target.

Directory of Open Access Journals (Sweden)

Yongsoon Kim

Full Text Available In C. elegans, the highly conserved DAF-2/insulin/insulin-like growth factor 1 receptor signaling (IIS pathway regulates longevity, metabolism, reproduction and development. In mammals, acid sphingomyelinase (ASM is an enzyme that hydrolyzes sphingomyelin to produce ceramide. ASM has been implicated in CD95 death receptor signaling under certain stress conditions. However, the involvement of ASM in growth factor receptor signaling under physiological conditions is not known. Here, we report that in vivo ASM functions as a positive regulator of the DAF-2/IIS pathway in C. elegans. We have shown that inactivation of asm-3 extends animal lifespan and promotes dauer arrest, an alternative developmental process. A significant cooperative effect on lifespan is observed between asm-3 deficiency and loss-of-function alleles of the age-1/PI 3-kinase, with the asm-3; age-1 double mutant animals having a mean lifespan 259% greater than that of the wild-type animals. The lifespan extension phenotypes caused by the loss of asm-3 are dependent on the functions of daf-16/FOXO and daf-18/PTEN. We have demonstrated that inactivation of asm-3 causes nuclear translocation of DAF-16::GFP protein, up-regulates endogenous DAF-16 protein levels and activates the downstream targeting genes of DAF-16. Together, our findings reveal a novel role of asm-3 in regulation of lifespan and diapause by modulating IIS pathway. Importantly, we have found that two drugs known to inhibit mammalian ASM activities, desipramine and clomipramine, markedly extend the lifespan of wild-type animals, in a manner similar to that achieved by genetic inactivation of the asm genes. Our studies illustrate a novel strategy of anti-aging by targeting ASM, which may potentially be extended to mammals.

ASM-3 acid sphingomyelinase functions as a positive regulator of the DAF-2/AGE-1 signaling pathway and serves as a novel anti-aging target.

Science.gov (United States)

Kim, Yongsoon; Sun, Hong

2012-01-01

In C. elegans, the highly conserved DAF-2/insulin/insulin-like growth factor 1 receptor signaling (IIS) pathway regulates longevity, metabolism, reproduction and development. In mammals, acid sphingomyelinase (ASM) is an enzyme that hydrolyzes sphingomyelin to produce ceramide. ASM has been implicated in CD95 death receptor signaling under certain stress conditions. However, the involvement of ASM in growth factor receptor signaling under physiological conditions is not known. Here, we report that in vivo ASM functions as a positive regulator of the DAF-2/IIS pathway in C. elegans. We have shown that inactivation of asm-3 extends animal lifespan and promotes dauer arrest, an alternative developmental process. A significant cooperative effect on lifespan is observed between asm-3 deficiency and loss-of-function alleles of the age-1/PI 3-kinase, with the asm-3; age-1 double mutant animals having a mean lifespan 259% greater than that of the wild-type animals. The lifespan extension phenotypes caused by the loss of asm-3 are dependent on the functions of daf-16/FOXO and daf-18/PTEN. We have demonstrated that inactivation of asm-3 causes nuclear translocation of DAF-16::GFP protein, up-regulates endogenous DAF-16 protein levels and activates the downstream targeting genes of DAF-16. Together, our findings reveal a novel role of asm-3 in regulation of lifespan and diapause by modulating IIS pathway. Importantly, we have found that two drugs known to inhibit mammalian ASM activities, desipramine and clomipramine, markedly extend the lifespan of wild-type animals, in a manner similar to that achieved by genetic inactivation of the asm genes. Our studies illustrate a novel strategy of anti-aging by targeting ASM, which may potentially be extended to mammals.

ASM-3 Acid Sphingomyelinase Functions as a Positive Regulator of the DAF-2/AGE-1 Signaling Pathway and Serves as a Novel Anti-Aging Target

Science.gov (United States)

Kim, Yongsoon; Sun, Hong

2012-01-01

In C. elegans, the highly conserved DAF-2/insulin/insulin-like growth factor 1 receptor signaling (IIS) pathway regulates longevity, metabolism, reproduction and development. In mammals, acid sphingomyelinase (ASM) is an enzyme that hydrolyzes sphingomyelin to produce ceramide. ASM has been implicated in CD95 death receptor signaling under certain stress conditions. However, the involvement of ASM in growth factor receptor signaling under physiological conditions is not known. Here, we report that in vivo ASM functions as a positive regulator of the DAF-2/IIS pathway in C. elegans. We have shown that inactivation of asm-3 extends animal lifespan and promotes dauer arrest, an alternative developmental process. A significant cooperative effect on lifespan is observed between asm-3 deficiency and loss-of-function alleles of the age-1/PI 3-kinase, with the asm-3; age-1 double mutant animals having a mean lifespan 259% greater than that of the wild-type animals. The lifespan extension phenotypes caused by the loss of asm-3 are dependent on the functions of daf-16/FOXO and daf-18/PTEN. We have demonstrated that inactivation of asm-3 causes nuclear translocation of DAF-16::GFP protein, up-regulates endogenous DAF-16 protein levels and activates the downstream targeting genes of DAF-16. Together, our findings reveal a novel role of asm-3 in regulation of lifespan and diapause by modulating IIS pathway. Importantly, we have found that two drugs known to inhibit mammalian ASM activities, desipramine and clomipramine, markedly extend the lifespan of wild-type animals, in a manner similar to that achieved by genetic inactivation of the asm genes. Our studies illustrate a novel strategy of anti-aging by targeting ASM, which may potentially be extended to mammals. PMID:23049887

The influence of floc size and hydraulic detention time on the performance of a dissolved air flotation (DAF) pilot unit in the light of a mathematical model.

Science.gov (United States)

Moruzzi, R B; Reali, M A P

2014-12-01

The influence of floc size and hydraulic detention time on the performance of a dissolved air flotation (DAF) pilot unit was investigated in the light of a known mathematical model. The following design and operational parameters were considered: the hydraulic detention time (tdcz) and hydraulic loading rate in the contact zone, the down-flow loading rate in the clarification zone, the particle size distribution (d F), and the recirculation rate (p). As a reference for DAF performance analysis, the proposed β.td parameter from the above mentioned mathematical model was employed. The results indicated that tdcz is an important factor in DAF performance and that d F and floc size are also determinants of DAF efficiency. Further, β.td was sensitive to both design and operational parameters, which were varied in the DAF pilot plant. The performance of the DAF unit decreases with increasing β.td values because a higher td (considering a fixed β) or a higher β (e.g., higher hydrophobicity of the flocs for a fixed td) would be necessary in the reaction zone to reach desired flotation efficiency.

Site-Directed Mutagenesis Study Revealed Three Important Residues in Hc-DAF-22, a Key Enzyme Regulating Diapause of Haemonchus contortus

Directory of Open Access Journals (Sweden)

Yan Huang

2017-11-01

Full Text Available Haemonchus contortus (H. contortus is one of the most important parasites of small ruminants, especially goats and sheep. The complex life cycle of this nematode is a main obstacle for the control and prevention of haemonchosis. So far, a special form of arrested development called diapause different from the dauer stage in Caenorhabditis elegans (C. elegans has been found in many parasitic nematodes. In our previous study, we have characterized a novel gene Hc-daf-22 from H. contortus sharing high homology with Ce-daf-22 and functional analysis showed this gene has similar biological function with Ce-daf-22. In this study, Hc-daf-22 mutants were constructed using site-directed mutagenesis, and carried out rescue experiments, RNA interference (RNAi experiments and in vitro enzyme activity analysis with the mutants to further explore the precise function site of Hc-DAF-22. The results showed that Hc-daf-22 mutants could be expressed in the rescued ok693 worms and the expression positions were mainly in the intestine which was identical with that of Hc-daf-22 rescued worms. Through lipid staining we found that Hc-daf-22 could rescue daf-22 mutant (ok693 from the fatty acid metabolism deficiency while Hc-daf-22 mutants failed. Brood size and body length analyses in rescue experiment along with body length and life span analyses in RNAi experiment elucidated that Hc-daf-22 resembled Ce-daf-22 in effecting the development and capacity of C. elegans and mutants impaired the function of Hc-daf-22. Together with the protease activity assay, this research revealed three important active resides 84C/299H/349H in Hc-DAF-22 by site-directed mutagenesis.

Site-Directed Mutagenesis Study Revealed Three Important Residues in Hc-DAF-22, a Key Enzyme Regulating Diapause of Haemonchus contortus.

Science.gov (United States)

Huang, Yan; Zheng, Xiuping; Zhang, Hongli; Ding, Haojie; Guo, Xiaolu; Yang, Yi; Chen, Xueqiu; Zhou, Qianjin; Du, Aifang

2017-01-01

Haemonchus contortus ( H. contortus ) is one of the most important parasites of small ruminants, especially goats and sheep. The complex life cycle of this nematode is a main obstacle for the control and prevention of haemonchosis. So far, a special form of arrested development called diapause different from the dauer stage in Caenorhabditis elegans ( C. elegans ) has been found in many parasitic nematodes. In our previous study, we have characterized a novel gene Hc-daf-22 from H. contortus sharing high homology with Ce-daf-22 and functional analysis showed this gene has similar biological function with Ce-daf-22 . In this study, Hc-daf-22 mutants were constructed using site-directed mutagenesis, and carried out rescue experiments, RNA interference (RNAi) experiments and in vitro enzyme activity analysis with the mutants to further explore the precise function site of Hc-DAF-22. The results showed that Hc-daf-22 mutants could be expressed in the rescued ok693 worms and the expression positions were mainly in the intestine which was identical with that of Hc-daf-22 rescued worms. Through lipid staining we found that Hc-daf-22 could rescue daf-22 mutant ( ok693 ) from the fatty acid metabolism deficiency while Hc-daf-22 mutants failed. Brood size and body length analyses in rescue experiment along with body length and life span analyses in RNAi experiment elucidated that Hc-daf-22 resembled Ce-daf-22 in effecting the development and capacity of C. elegans and mutants impaired the function of Hc-daf-22 . Together with the protease activity assay, this research revealed three important active resides 84C/299H/349H in Hc-DAF-22 by site-directed mutagenesis.

DAF-16 and Δ9 desaturase genes promote cold tolerance in long-lived Caenorhabditis elegans age-1 mutants.

Directory of Open Access Journals (Sweden)

Fiona R Savory

Full Text Available In Caenorhabditis elegans, mutants of the conserved insulin/IGF-1 signalling (IIS pathway are long-lived and stress resistant due to the altered expression of DAF-16 target genes such as those involved in cellular defence and metabolism. The three Δ(9 desaturase genes, fat-5, fat-6 and fat-7, are included amongst these DAF-16 targets, and it is well established that Δ(9 desaturase enzymes play an important role in survival at low temperatures. However, no assessment of cold tolerance has previously been reported for IIS mutants. We demonstrate that long-lived age-1(hx546 mutants are remarkably resilient to low temperature stress relative to wild type worms, and that this is dependent upon daf-16. We also show that cold tolerance following direct transfer to low temperatures is increased in wild type worms during the facultative, daf-16 dependent, dauer stage. Although the cold tolerant phenotype of age-1(hx546 mutants is predominantly due to the Δ(9 desaturase genes, additional transcriptional targets of DAF-16 are also involved. Surprisingly, survival of wild type adults following a rapid temperature decline is not dependent upon functional daf-16, and cellular distributions of a DAF-16::GFP fusion protein indicate that DAF-16 is not activated during low temperature stress. This suggests that cold-induced physiological defences are not specifically regulated by the IIS pathway and DAF-16, but expression of DAF-16 target genes in IIS mutants and dauers is sufficient to promote cross tolerance to low temperatures in addition to other forms of stress.

A study on some welfare-related parameters of hDAF transgenic pigs when compared with their conventional close relatives.

Science.gov (United States)

Martelli, G; Sardi, L; Stancampiano, L; Govoni, N; Zannoni, A; Nannoni, E; Forni, M; Bacci, M L

2014-05-01

Pigs are increasingly used in medical research as transgenic laboratory animals; however, little knowledge is presently available concerning their welfare assessment. The aim of the present study was to investigate some welfare-related parameters of transgenic pigs intended for xenotrasplantation (human decay-accelerating factor (hDAF)) when compared with their conventional (i.e. not transgenic) close relatives (full sibs and half sibs). A total of 14 Large White female transgenic pigs and 10 female non-transgenic (conventional) pigs from four litters were used. All pigs were from the same conventional boar, donor of the semen treated for sperm-mediated gene transfer. During the experiment, BW ranged from 50 to about 80 kg and pigs were weighed at the beginning and at the end of the experiment. Animals were subjected to a set of behavioural tests: a human approach test (HAT), a novel object test (NOT) and an open-door test (ODT). Food preferences were tested through the offer of different foods (banana, apple, carrot, cracker and lemon). During a 4-day period, pigs were diurnally videotaped to study the prevalence of the different behaviours and social interactions (aggressive and non-aggressive interactions). At the end of the trial, cortisol level had been assessed on bristles. No significant differences (P>0.05) were observed between hDAF transgenic and conventional pigs with respect to growth traits, reactivity towards unexpected situations (HAT, NOT, ODT), food preferences, main behavioural traits, social interactions and hair cortisol.

Oleanolic acid activates daf-16 to increase lifespan in Caenorhabditis elegans

International Nuclear Information System (INIS)

Zhang, Jiaolong; Lu, Lulu; Zhou, Lijun

2015-01-01

Oleanolic acid (OA) is an active ingredient in natural plants. It has been reported to possess a variety of pharmacological activities, but very little is known about its effects of anti-aging. We investigate here whether OA has an impact on longevity in vivo, and more specifically, we have examined effects of OA on the lifespan and stress tolerance in Caenorhabditis elegans (C. elegans). Our results showed that OA could extend the lifespan, increase its stress resistance and reduce the intracellular reactive oxygen species (ROS) in wild-type worms. Moreover, we have found that OA-induced longevity may not be associated with the calorie restriction (CR) mechanism. Our mechanistic studies using daf-16 loss-of-function mutant strains (GR1307) indicated that the extension of lifespan by OA requires daf-16. In addition, OA treatment could also modulate the nuclear localization, and the quantitative real-time PCR results revealed that up-regulation of daf-16 target genes such as sod-3, hsp-16.2 and ctl-1 could prolong lifespan and increase stress response in C. elegans. This study overall uncovers the longevity effect of OA and its underpinning mechanisms. - Graphical abstract: Oleanolic acid modulates the activity of DAF-16 to promote longevity and increase stress resistance in Caenorhabditis elegans. - Highlights: • OA extends the lifespan of wild-type Caenorhabditis elegans. • OA improves the stress resistance and reduces the intracellular ROS level in C. elegans. • OA induces lifespan extension may not proceed through the CR mechanism. • OA extends the lifespan in C. elegans is modulated by daf-16.

Oleanolic acid activates daf-16 to increase lifespan in Caenorhabditis elegans

Energy Technology Data Exchange (ETDEWEB)

Zhang, Jiaolong; Lu, Lulu; Zhou, Lijun, E-mail: lijunzhou@tju.edu.cn

2015-12-25

Oleanolic acid (OA) is an active ingredient in natural plants. It has been reported to possess a variety of pharmacological activities, but very little is known about its effects of anti-aging. We investigate here whether OA has an impact on longevity in vivo, and more specifically, we have examined effects of OA on the lifespan and stress tolerance in Caenorhabditis elegans (C. elegans). Our results showed that OA could extend the lifespan, increase its stress resistance and reduce the intracellular reactive oxygen species (ROS) in wild-type worms. Moreover, we have found that OA-induced longevity may not be associated with the calorie restriction (CR) mechanism. Our mechanistic studies using daf-16 loss-of-function mutant strains (GR1307) indicated that the extension of lifespan by OA requires daf-16. In addition, OA treatment could also modulate the nuclear localization, and the quantitative real-time PCR results revealed that up-regulation of daf-16 target genes such as sod-3, hsp-16.2 and ctl-1 could prolong lifespan and increase stress response in C. elegans. This study overall uncovers the longevity effect of OA and its underpinning mechanisms. - Graphical abstract: Oleanolic acid modulates the activity of DAF-16 to promote longevity and increase stress resistance in Caenorhabditis elegans. - Highlights: • OA extends the lifespan of wild-type Caenorhabditis elegans. • OA improves the stress resistance and reduces the intracellular ROS level in C. elegans. • OA induces lifespan extension may not proceed through the CR mechanism. • OA extends the lifespan in C. elegans is modulated by daf-16.

DAFS Storage for High Performance Computing Using MPI-I/O: Design and Experience

National Research Council Canada - National Science Library

Velusamy, Vijay

2004-01-01

.... DAFS is a well-defined highperformance protocol for file access across a network as well as set of APIs, uDAFS, for user level OS-bypassing application programming, designed to take advantage of RDMA-based transports, such as Virtual Interface Architecture (VIA), InfiniBand Architecture1, and iWARP.

The thioredoxin TRX-1 modulates the function of the insulin-like neuropeptide DAF-28 during dauer formation in Caenorhabditis elegans.

Science.gov (United States)

Fierro-González, Juan Carlos; Cornils, Astrid; Alcedo, Joy; Miranda-Vizuete, Antonio; Swoboda, Peter

2011-01-27

Thioredoxins comprise a conserved family of redox regulators involved in many biological processes, including stress resistance and aging. We report that the C. elegans thioredoxin TRX-1 acts in ASJ head sensory neurons as a novel modulator of the insulin-like neuropeptide DAF-28 during dauer formation. We show that increased formation of stress-resistant, long-lived dauer larvae in mutants for the gene encoding the insulin-like neuropeptide DAF-28 requires TRX-1 acting in ASJ neurons, upstream of the insulin-like receptor DAF-2. Genetic rescue experiments demonstrate that redox-independent functions of TRX-1 specifically in ASJ neurons are needed for the dauer formation constitutive (Daf-c) phenotype of daf-28 mutants. GFP reporters of trx-1 and daf-28 show opposing expression patterns in dauers (i.e. trx-1 is up-regulated and daf-28 is down-regulated), an effect that is not observed in growing L2/L3 larvae. In addition, functional TRX-1 is required for the down-regulation of a GFP reporter of daf-28 during dauer formation, a process that is likely subject to DAF-28-mediated feedback regulation. Our findings demonstrate that TRX-1 modulates DAF-28 signaling by contributing to the down-regulation of daf-28 expression during dauer formation. We propose that TRX-1 acts as a fluctuating neuronal signaling modulator within ASJ neurons to monitor the adjustment of neuropeptide expression, including insulin-like proteins, during dauer formation in response to adverse environmental conditions.

Kinetic analysis of DAF-FM activation by NO: toward calibration of a NO-sensitive fluorescent dye.

Science.gov (United States)

Namin, Shabnam M; Nofallah, Sara; Joshi, Mahesh S; Kavallieratos, Konstantinos; Tsoukias, Nikolaos M

2013-01-15

Nitric oxide (NO) research in biomedicine has been hampered by the absence of a method that will allow quantitative measurement of NO in biological tissues with high sensitivity and selectivity, and with adequate spatial and temporal resolution. 4-amino-5-methylamino-2',7'-difluorofluorescein (DAF-FM) is a NO sensitive fluorescence probe that has been used widely for qualitative assessment of cellular NO production. However, calibration of the fluorescent signal and quantification of NO concentration in cells and tissues using fluorescent probes, have provided significant challenge. In this study we utilize a combination of mathematical modeling and experimentation to elucidate the kinetics of NO/DAF-FM reaction in solution. Modeling and experiments suggest that the slope of fluorescent intensity (FI) can be related to NO concentration according to the equation: ddtFI=2αk(1)NO(2)O(2)DAF-FMkNO+DAF-FM where α is a proportionality coefficient that relates FI to unit concentration of activated DAF-FM, k(1) is the NO oxidation rate constant, and k was estimated to be 4.3±0.6. The FI slope exhibits saturation kinetics with DAF-FM concentration. Interestingly, the effective half-maximum constant (EC(50)) increases proportionally to NO concentration. This result is not in agreement with the proposition that N(2)O(3) is the NO oxidation byproduct that activates DAF-FM. Kinetic analysis suggests that the reactive intermediate should exhibit NO-dependent consumption and thus NO(2)() is a more likely candidate. The derived rate law can be used for the calibration of DAF-FM fluorescence and the quantification of NO concentration in biological tissues. Copyright © 2012 Elsevier Inc. All rights reserved.

Increased Protein Stability and Decreased Protein Turnover in the Caenorhabditis elegans Ins/IGF-1 daf-2 Mutant.

Science.gov (United States)

Depuydt, Geert; Shanmugam, Nilesh; Rasulova, Madina; Dhondt, Ineke; Braeckman, Bart P

2016-12-01

In Caenorhabditis elegans, cellular proteostasis is likely essential for longevity. Autophagy has been shown to be essential for lifespan extension of daf-2 insulin/IGF mutants. Therefore, it can be hypothesized that daf-2 mutants achieve this phenotype by increasing protein turnover. However, such a mechanism would exert a substantial energy cost. By using classical 35 S pulse-chase labeling, we observed that protein synthesis and degradation rates are decreased in young adults of the daf-2 insulin/IGF mutants. Although reduction of protein turnover may be energetically favorable, it may lead to accumulation and aggregation of damaged proteins. As this has been shown not to be the case in daf-2 mutants, another mechanism must exist to maintain proteostasis in this strain. We observed that proteins isolated from daf-2 mutants are more soluble in acidic conditions due to increased levels of trehalose. This suggests that trehalose may decrease the potential for protein aggregation and increases proteostasis in the daf-2 mutants. We postulate that daf-2 mutants save energy by decreasing protein turnover rates and instead stabilize their proteome by trehalose. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America.

The thioredoxin TRX-1 modulates the function of the insulin-like neuropeptide DAF-28 during dauer formation in Caenorhabditis elegans.

Directory of Open Access Journals (Sweden)

Juan Carlos Fierro-González

2011-01-01

Full Text Available Thioredoxins comprise a conserved family of redox regulators involved in many biological processes, including stress resistance and aging. We report that the C. elegans thioredoxin TRX-1 acts in ASJ head sensory neurons as a novel modulator of the insulin-like neuropeptide DAF-28 during dauer formation. We show that increased formation of stress-resistant, long-lived dauer larvae in mutants for the gene encoding the insulin-like neuropeptide DAF-28 requires TRX-1 acting in ASJ neurons, upstream of the insulin-like receptor DAF-2. Genetic rescue experiments demonstrate that redox-independent functions of TRX-1 specifically in ASJ neurons are needed for the dauer formation constitutive (Daf-c phenotype of daf-28 mutants. GFP reporters of trx-1 and daf-28 show opposing expression patterns in dauers (i.e. trx-1 is up-regulated and daf-28 is down-regulated, an effect that is not observed in growing L2/L3 larvae. In addition, functional TRX-1 is required for the down-regulation of a GFP reporter of daf-28 during dauer formation, a process that is likely subject to DAF-28-mediated feedback regulation. Our findings demonstrate that TRX-1 modulates DAF-28 signaling by contributing to the down-regulation of daf-28 expression during dauer formation. We propose that TRX-1 acts as a fluctuating neuronal signaling modulator within ASJ neurons to monitor the adjustment of neuropeptide expression, including insulin-like proteins, during dauer formation in response to adverse environmental conditions.

ins-7 Gene expression is partially regulated by the DAF-16/IIS signaling pathway in Caenorhabditis elegans under celecoxib intervention.

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Shanqing Zheng

Full Text Available DAF-16 target genes are employed as reporters of the insulin/IGF-1 like signal pathway (IIS, and this is notably true when Caenorhabditis elegans (C. elegans is used to study the action of anti-aging compounds on IIS activity. However, some of these genes may not be specific to DAF-16, even if their expression levels are altered when DAF-16 is activated. Celecoxib was reported to extend the lifespan of C. elegans through activation of DAF-16. Our results confirmed the function of celecoxib on aging; however, we found that the expression of ins-7, a DAF-16 target gene, was abnormally regulated by celecoxib. ins-7 plays an important role in regulating aging, and its expression is suppressed in C. elegans when DAF-16 is activated. However, we found that celecoxib upregulated the expression of ins-7 in contrast to its role in DAF-16 activation. Our subsequent analysis indicated that the expression level of ins-7 in C. elegans was negatively regulated by DAF-16 activity. Additionally, its expression was also positively regulated by DAF-16-independent mechanisms, at least following external pharmacological intervention. Our study suggests that ins-7 is not a specific target gene of DAF-16, and should not be chosen as a reporter for IIS activity. This conclusion is important in the study of INSs on aging in C. elegans, especially under the circumstance of drug intervention.

ins-7 Gene expression is partially regulated by the DAF-16/IIS signaling pathway in Caenorhabditis elegans under celecoxib intervention.

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Zheng, Shanqing; Liao, Sentai; Zou, Yuxiao; Qu, Zhi; Liu, Fan

2014-01-01

DAF-16 target genes are employed as reporters of the insulin/IGF-1 like signal pathway (IIS), and this is notably true when Caenorhabditis elegans (C. elegans) is used to study the action of anti-aging compounds on IIS activity. However, some of these genes may not be specific to DAF-16, even if their expression levels are altered when DAF-16 is activated. Celecoxib was reported to extend the lifespan of C. elegans through activation of DAF-16. Our results confirmed the function of celecoxib on aging; however, we found that the expression of ins-7, a DAF-16 target gene, was abnormally regulated by celecoxib. ins-7 plays an important role in regulating aging, and its expression is suppressed in C. elegans when DAF-16 is activated. However, we found that celecoxib upregulated the expression of ins-7 in contrast to its role in DAF-16 activation. Our subsequent analysis indicated that the expression level of ins-7 in C. elegans was negatively regulated by DAF-16 activity. Additionally, its expression was also positively regulated by DAF-16-independent mechanisms, at least following external pharmacological intervention. Our study suggests that ins-7 is not a specific target gene of DAF-16, and should not be chosen as a reporter for IIS activity. This conclusion is important in the study of INSs on aging in C. elegans, especially under the circumstance of drug intervention.

daf-16/FoxO promotes gluconeogenesis and trehalose synthesis during starvation to support survival.

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Hibshman, Jonathan D; Doan, Alexander E; Moore, Brad T; Kaplan, Rebecca Ew; Hung, Anthony; Webster, Amy K; Bhatt, Dhaval P; Chitrakar, Rojin; Hirschey, Matthew D; Baugh, L Ryan

2017-10-24

daf-16 /FoxO is required to survive starvation in Caenorhabditis elegans , but how daf-16I FoxO promotes starvation resistance is unclear. We show that daf-16 /FoxO restructures carbohydrate metabolism by driving carbon flux through the glyoxylate shunt and gluconeogenesis and into synthesis of trehalose, a disaccharide of glucose. Trehalose is a well-known stress protectant, capable of preserving membrane organization and protein structure during abiotic stress. Metabolomic, genetic, and pharmacological analyses confirm increased trehalose synthesis and further show that trehalose not only supports survival as a stress protectant but also serves as a glycolytic input. Furthermore, we provide evidence that metabolic cycling between trehalose and glucose is necessary for this dual function of trehalose. This work demonstrates that daf-16 /FoxO promotes starvation resistance by shifting carbon metabolism to drive trehalose synthesis, which in turn supports survival by providing an energy source and acting as a stress protectant.

daf-16/FoxO promotes gluconeogenesis and trehalose synthesis during starvation to support survival

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Hibshman, Jonathan D; Doan, Alexander E; Moore, Brad T; Kaplan, Rebecca EW; Hung, Anthony; Webster, Amy K; Bhatt, Dhaval P; Chitrakar, Rojin; Hirschey, Matthew D

2017-01-01

daf-16/FoxO is required to survive starvation in Caenorhabditis elegans, but how daf-16IFoxO promotes starvation resistance is unclear. We show that daf-16/FoxO restructures carbohydrate metabolism by driving carbon flux through the glyoxylate shunt and gluconeogenesis and into synthesis of trehalose, a disaccharide of glucose. Trehalose is a well-known stress protectant, capable of preserving membrane organization and protein structure during abiotic stress. Metabolomic, genetic, and pharmacological analyses confirm increased trehalose synthesis and further show that trehalose not only supports survival as a stress protectant but also serves as a glycolytic input. Furthermore, we provide evidence that metabolic cycling between trehalose and glucose is necessary for this dual function of trehalose. This work demonstrates that daf-16/FoxO promotes starvation resistance by shifting carbon metabolism to drive trehalose synthesis, which in turn supports survival by providing an energy source and acting as a stress protectant. PMID:29063832

The solution structure of the forkhead box-O DNA binding domain of Brugia malayi DAF-16a.

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Casper, Sarah K; Schoeller, Scott J; Zgoba, Danielle M; Phillips, Andrew J; Morien, Thomas J; Chaffee, Gary R; Sackett, Peter C; Peterson, Francis C; Crossgrove, Kirsten; Veldkamp, Christopher T

2014-12-01

Brugia malayi is a parasitic nematode that causes lymphatic filariasis in humans. Here the solution structure of the forkhead DNA binding domain of Brugia malayi DAF-16a, a putative ortholog of Caenorhabditis elegans DAF-16, is reported. It is believed to be the first structure of a forkhead or winged helix domain from an invertebrate. C. elegans DAF-16 is involved in the insulin/IGF-I signaling pathway and helps control metabolism, longevity, and development. Conservation of sequence and structure with human FOXO proteins suggests that B. malayi DAF-16a is a member of the FOXO family of forkhead proteins. © 2014 Wiley Periodicals, Inc.

Device Assembly Facility (DAF) Glovebox Radioactive Waste Characterization

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Dominick, J L

2001-01-01

The Device Assembly Facility (DAF) at the Nevada Test Site (NTS) provides programmatic support to the Joint Actinide Shock Physics Experimental Research (JASPER) Facility in the form of target assembly. The target assembly activities are performed in a glovebox at DAF and include Special Nuclear Material (SNM). Currently, only activities with transuranic SNM are anticipated. Preliminary discussions with facility personnel indicate that primarily two distributions of SNM will be used: Weapons Grade Plutonium (WG-Pu), and Pu-238 enhanced WG-Pu. Nominal radionuclide distributions for the two material types are included in attachment 1. Wastes generated inside glove boxes is expected to be Transuranic (TRU) Waste which will eventually be disposed of at the Waste Isolation Pilot Plant (WIPP). Wastes generated in the Radioactive Material Area (RMA), outside of the glove box is presumed to be low level waste (LLW) which is destined for disposal at the NTS. The process knowledge quantification methods identified herein may be applied to waste generated anywhere within or around the DAF and possibly JASPER as long as the fundamental waste stream boundaries are adhered to as outlined below. The method is suitable for quantification of waste which can be directly surveyed with the Blue Alpha meter or swiped. An additional quantification methodology which requires the use of a high resolution gamma spectroscopy unit is also included and relies on the predetermined radionuclide distribution and utilizes scaling to measured nuclides for quantification

The longevity effect of echinacoside in Caenorhabditis elegans mediated through daf-16.

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Wang, Xue; Zhang, Jiaolong; Lu, Lulu; Zhou, Lijun

2015-01-01

Echinacoside (ECH), a natural polyphenolic compound, has been reported to possess important pharmacological activities. However, very little is known about whether or how ECH affects longevity in vivo. We have examined the effects of ECH on the life span and stress tolerance in Caenorhabditis elegans. Our studies demonstrate that the life span of wild-type worms could be extended in the presence of ECH. Furthermore, ECH was found to increase tolerance of worms to heat shock and oxidative stress, while not exerting any influence on pharyngeal pumping rate and progeny production. Our mechanistic studies indicate that supplementation of ECH increases the transcript level of daf-16. ECH treatment also modulates the nuclear localization and transcriptional activities of daf-16, thus fine tunes the expression of daf-16 target genes to promote longevity and increases stress response in C. elegans. Overall, this work reveals the longevity effect of ECH and elucidates the underpinning mechanisms.

Regulation of lead toxicity by heat shock protein 90 (daf-21) is affected by temperature in Caenorhabditis elegans.

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Wang, Yunbiao; Xu, Songbai; Liu, Jing; Zhang, Yanhui; Guo, Tai L

2014-06-01

In the nematode Caenorhabditis elegans, stress resistance can be regulated by dauer formation (daf) genes. In the present study, regulation of heavy metal lead (Pb) toxicity by the 90-kDa heat shock proteins (Hsp90; daf-21) was investigated in both wild-type C. elegans and daf-21/Hsp90 mutants by focusing on the effects of varied temperatures below (15°C) or above (25 and 30°C) the presumptive optimum growth temperature (20°C). More acute toxicity of Pb, indicated by the 24-h median lethal concentrations (LC50), was observed in wild-type adults than in the daf-21 mutant adults at 15, 20 and 25°C; however, the daf-21 mutant adults showed more sensitivity at 30°C. Enhanced Pb sensitivity (e.g., decrease LC50) in both types of C. elegans was observed with both increased and decreased temperatures when compared to that at 20°C. Additional examined endpoints included time course of toxicity at LC50s, pharyngeal pumping, reproduction, life span, and Hsp90 expression. Collective results showed that temperatures both above and below 20°C exacerbated Pb toxicity, and that the protein level of daf-21/Hsp90 was one of the most sensitive indicators of Pb toxicity in wild-type C. elegans, while pharyngeal pumping was more Pb sensitive in daf-21 mutants. Therefore, the expression of daf-21/Hsp90 has apparent utility for the prediction and assessment of Pb-induced toxicity in nematodes. Further, the stress responses related to Hsp90 expression in C. elegans may have considerable potential as sensitive biomarkers for the monitoring of environmental Pb contamination. Copyright © 2014 Elsevier Inc. All rights reserved.

Catalpol Modulates Lifespan via DAF-16/FOXO and SKN-1/Nrf2 Activation in Caenorhabditis elegans

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Hyun Won Seo

2015-01-01

Full Text Available Catalpol is an effective component of rehmannia root and known to possess various pharmacological properties. The present study was aimed at investigating the potential effects of catalpol on the lifespan and stress tolerance using C. elegans model system. Herein, catalpol showed potent lifespan extension of wild-type nematode under normal culture condition. In addition, survival rate of catalpol-fed nematodes was significantly elevated compared to untreated control under heat and oxidative stress but not under hyperosmolality conditions. We also found that elevated antioxidant enzyme activities and expressions of stress resistance proteins were attributed to catalpol-mediated increased stress tolerance of nematode. We further investigated whether catalpol’s longevity effect is related to aging-related factors including reproduction, food intake, and growth. Interestingly, catalpol exposure could attenuate pharyngeal pumping rate, indicating that catalpol may induce dietary restriction of nematode. Moreover, locomotory ability of aged nematode was significantly improved by catalpol treatment, while lipofuscin levels were attenuated, suggesting that catalpol may affect age-associated changes of nematode. Our mechanistic studies revealed that mek-1, daf-2, age-1, daf-16, and skn-1 are involved in catalpol-mediated longevity. These results indicate that catalpol extends lifespan and increases stress tolerance of C. elegans via DAF-16/FOXO and SKN-1/Nrf activation dependent on insulin/IGF signaling and JNK signaling.

Rifampicin reduces advanced glycation end products and activates DAF-16 to increase lifespan in Caenorhabditis elegans.

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Golegaonkar, Sandeep; Tabrez, Syed S; Pandit, Awadhesh; Sethurathinam, Shalini; Jagadeeshaprasad, Mashanipalya G; Bansode, Sneha; Sampathkumar, Srinivasa-Gopalan; Kulkarni, Mahesh J; Mukhopadhyay, Arnab

2015-06-01

Advanced glycation end products (AGEs) are formed when glucose reacts nonenzymatically with proteins; these modifications are implicated in aging and pathogenesis of many age-related diseases including type II diabetes, atherosclerosis, and neurodegenerative disorders. Thus, pharmaceutical interventions that can reduce AGEs may delay age-onset diseases and extend lifespan. Using LC-MS(E), we show that rifampicin (RIF) reduces glycation of important cellular proteins in vivo and consequently increases lifespan in Caenorhabditis elegans by up to 60%. RIF analog rifamycin SV (RSV) possesses similar properties, while rifaximin (RMN) lacks antiglycation activity and therefore fails to affect lifespan positively. The efficacy of RIF and RSV as potent antiglycating agents may be attributed to the presence of a p-dihydroxyl moiety that can potentially undergo spontaneous oxidation to yield highly reactive p-quinone structures, a feature absent in RMN. We also show that supplementing rifampicin late in adulthood is sufficient to increase lifespan. For its effect on longevity, rifampicin requires DAF-18 (nematode PTEN) as well as JNK-1 and activates DAF-16, the FOXO homolog. Interestingly, the drug treatment modulates transcription of a different subset of DAF-16 target genes, those not controlled by the conserved Insulin-IGF-1-like signaling pathway. RIF failed to increase the lifespan of daf-16 null mutant despite reducing glycation, showing thereby that DAF-16 may not directly affect AGE formation. Together, our data suggest that the dual ability to reduce glycation in vivo and activate prolongevity processes through DAF-16 makes RIF and RSV effective lifespan-extending interventions. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Gαo and Gαq regulate the expression of daf-7, a TGFβ-like gene, in Caenorhabditis elegans.

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Edith M Myers

Full Text Available Caenorhabditis elegans enter an alternate developmental stage called dauer in unfavorable conditions such as starvation, overcrowding, or high temperature. Several evolutionarily conserved signaling pathways control dauer formation. DAF-7/TGFβ and serotonin, important ligands in these signaling pathways, affect not only dauer formation, but also the expression of one another. The heterotrimeric G proteins GOA-1 (Gα(o and EGL-30 (Gα(q mediate serotonin signaling as well as serotonin biosynthesis in C. elegans. It is not known whether GOA-1 or EGL-30 also affect dauer formation and/or daf-7 expression, which are both modulated in part by serotonin. The purpose of this study is to better understand the relationship between proteins important for neuronal signaling and developmental plasticity in both C. elegans and humans. Using promoter-GFP transgenic worms, it was determined that both goa-1 and egl-30 regulate daf-7 expression during larval development. In addition, the normal daf-7 response to high temperature or starvation was altered in goa-1 and egl-30 mutants. Despite the effect of goa-1 and egl-30 mutations on daf-7 expression in various environmental conditions, there was no effect of the mutations on dauer formation. This paper provides evidence that while goa-1 and egl-30 are important for normal daf-7 expression, mutations in these genes are not sufficient to disrupt dauer formation.

Decay-accelerating factor 1 deficiency exacerbates leptospiral-induced murine chronic nephritis and renal fibrosis.

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María F Ferrer

Full Text Available Leptospirosis is a global zoonosis caused by pathogenic Leptospira, which can colonize the proximal renal tubules and persist for long periods in the kidneys of infected hosts. Here, we characterized the infection of C57BL/6J wild-type and Daf1-/- mice, which have an enhanced host response, with a virulent Leptospira interrogans strain at 14 days post-infection, its persistence in the kidney, and its link to kidney fibrosis at 90 days post-infection. We found that Leptospira interrogans can induce acute moderate nephritis in wild-type mice and is able to persist in some animals, inducing fibrosis in the absence of mortality. In contrast, Daf1-/- mice showed acute mortality, with a higher bacterial burden. At the chronic stage, Daf1-/- mice showed greater inflammation and fibrosis than at 14 days post-infection and higher levels at all times than the wild-type counterpart. Compared with uninfected mice, infected wild-type mice showed higher levels of IL-4, IL-10 and IL-13, with similar levels of α-smooth muscle actin, galectin-3, TGF-β1, IL-17, IFN-γ, and lower IL-12 levels at 90 days post-infection. In contrast, fibrosis in Daf1-/- mice was accompanied by high expression of α-smooth muscle actin, galectin-3, IL-10, IL-13, and IFN-γ, similar levels of TGF-β1, IL-12, and IL-17 and lower IL-4 levels. This study demonstrates the link between Leptospira-induced murine chronic nephritis with renal fibrosis and shows a protective role of Daf1.

Activated AKT/PKB signaling in C. elegans uncouples temporally distinct outputs of DAF-2/insulin-like signaling

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Hanselman Keaton B

2006-10-01

Full Text Available Abstract Background In the nematode, Caenorhabditis elegans, a conserved insulin-like signaling pathway controls larval development, stress resistance and adult lifespan. AGE-1, a homolog of the p110 catalytic subunit of phosphoinositide 3-kinases (PI3K comprises the major known effector pathway downstream of the insulin receptor, DAF-2. Phospholipid products of AGE-1/PI3K activate AKT/PKB kinase signaling via PDK-1. AKT/PKB signaling antagonizes nuclear translocation of the DAF-16/FOXO transcription factor. Reduced AGE-1/PI3K signaling permits DAF-16 to direct dauer larval arrest and promote long lifespan in adult animals. In order to study the downstream effectors of AGE-1/PI3K signaling in C. elegans, we conducted a genetic screen for mutations that suppress the constitutive dauer arrest phenotype of age-1(mg109 animals. Results This report describes mutations recovered in a screen for suppressors of the constitutive dauer arrest (daf-C phenotype of age-1(mg109. Two mutations corresponded to alleles of daf-16. Two mutations were gain-of-function alleles in the genes, akt-1 and pdk-1, encoding phosphoinositide-dependent serine/threonine kinases. A fifth mutation, mg227, located on chromosome X, did not correspond to any known dauer genes, suggesting that mg227 may represent a new component of the insulin pathway. Genetic epistasis analysis by RNAi showed that reproductive development in age-1(mg109;akt-1(mg247 animals was dependent on the presence of pdk-1. Similarly, reproductive development in age-1(mg109;pdk-1(mg261 animals was dependent on akt-1. However, reproductive development in age-1(mg109; mg227 animals required only akt-1, and pdk-1 activity was dispensable in this background. Interestingly, while mg227 suppressed dauer arrest in age-1(mg109 animals, it enhanced the long lifespan phenotype. In contrast, akt-1(mg247 and pdk-1(mg261 did not affect lifespan or stress resistance, while both daf-16 alleles fully suppressed these

Activated AKT/PKB signaling in C. elegans uncouples temporally distinct outputs of DAF-2/insulin-like signaling.

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Gami, Minaxi S; Iser, Wendy B; Hanselman, Keaton B; Wolkow, Catherine A

2006-10-04

In the nematode, Caenorhabditis elegans, a conserved insulin-like signaling pathway controls larval development, stress resistance and adult lifespan. AGE-1, a homolog of the p110 catalytic subunit of phosphoinositide 3-kinases (PI3K) comprises the major known effector pathway downstream of the insulin receptor, DAF-2. Phospholipid products of AGE-1/PI3K activate AKT/PKB kinase signaling via PDK-1. AKT/PKB signaling antagonizes nuclear translocation of the DAF-16/FOXO transcription factor. Reduced AGE-1/PI3K signaling permits DAF-16 to direct dauer larval arrest and promote long lifespan in adult animals. In order to study the downstream effectors of AGE-1/PI3K signaling in C. elegans, we conducted a genetic screen for mutations that suppress the constitutive dauer arrest phenotype of age-1(mg109) animals. This report describes mutations recovered in a screen for suppressors of the constitutive dauer arrest (daf-C) phenotype of age-1(mg109). Two mutations corresponded to alleles of daf-16. Two mutations were gain-of-function alleles in the genes, akt-1 and pdk-1, encoding phosphoinositide-dependent serine/threonine kinases. A fifth mutation, mg227, located on chromosome X, did not correspond to any known dauer genes, suggesting that mg227 may represent a new component of the insulin pathway. Genetic epistasis analysis by RNAi showed that reproductive development in age-1(mg109);akt-1(mg247) animals was dependent on the presence of pdk-1. Similarly, reproductive development in age-1(mg109);pdk-1(mg261) animals was dependent on akt-1. However, reproductive development in age-1(mg109); mg227 animals required only akt-1, and pdk-1 activity was dispensable in this background. Interestingly, while mg227 suppressed dauer arrest in age-1(mg109) animals, it enhanced the long lifespan phenotype. In contrast, akt-1(mg247) and pdk-1(mg261) did not affect lifespan or stress resistance, while both daf-16 alleles fully suppressed these phenotypes. A screen for suppressors of PI3K

Context-dependent regulation of feeding behaviour by the insulin receptor, DAF-2, in Caenorhabditis elegans.

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Dillon, James; Holden-Dye, Lindy; O'Connor, Vincent; Hopper, Neil A

2016-06-01

Insulin signalling plays a significant role in both developmental programmes and pathways modulating the neuronal signalling that controls adult behaviour. Here, we have investigated insulin signalling in food-associated behaviour in adult C. elegans by scoring locomotion and feeding on and off bacteria, the worm's food. This analysis used mutants (daf-2, daf-18) of the insulin signalling pathway, and we provide evidence for an acute role for insulin signalling in the adult nervous system distinct from its impact on developmental programmes. Insulin receptor daf-2 mutants move slower than wild type both on and off food and showed impaired locomotory responses to food deprivation. This latter behaviour is manifest as a failure to instigate dispersal following prolonged food deprivation and suggests a role for insulin signalling in this adaptive response. Insulin receptor daf-2 mutants are also deficient in pharyngeal pumping on food and off food. Pharmacological analysis showed the pharynx of daf-2 is selectively compromised in its response to 5-HT compared to the excitatory neuropeptide FLP-17. By comparing the adaptive pharyngeal behaviour in intact worms and isolated pharyngeal preparations, we determined that an insulin-dependent signal extrinsic to the pharyngeal system is involved in feeding adaptation. Hence, we suggest that reactive insulin signalling modulates both locomotory foraging and pharyngeal pumping as the animal adapts to the absence of food. We discuss this in the context of insulin signalling directing a shift in the sensitivity of neurotransmitter systems to regulate the worm's response to changes in food availability in the environment.

Oleanolic acid activates daf-16 to increase lifespan in Caenorhabditis elegans.

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Zhang, Jiaolong; Lu, Lulu; Zhou, Lijun

2015-12-25

Oleanolic acid (OA) is an active ingredient in natural plants. It has been reported to possess a variety of pharmacological activities, but very little is known about its effects of anti-aging. We investigate here whether OA has an impact on longevity in vivo, and more specifically, we have examined effects of OA on the lifespan and stress tolerance in Caenorhabditis elegans (C. elegans). Our results showed that OA could extend the lifespan, increase its stress resistance and reduce the intracellular reactive oxygen species (ROS) in wild-type worms. Moreover, we have found that OA-induced longevity may not be associated with the calorie restriction (CR) mechanism. Our mechanistic studies using daf-16 loss-of-function mutant strains (GR1307) indicated that the extension of lifespan by OA requires daf-16. In addition, OA treatment could also modulate the nuclear localization, and the quantitative real-time PCR results revealed that up-regulation of daf-16 target genes such as sod-3, hsp-16.2 and ctl-1 could prolong lifespan and increase stress response in C. elegans. This study overall uncovers the longevity effect of OA and its underpinning mechanisms. Copyright © 2015 Elsevier Inc. All rights reserved.

Evaluation of Dissolved Air Flotation (DAF for Pretreatment of the Karoon River Water

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Naeim Banisaeid

2007-09-01

Full Text Available The efficiency of a pilot dissolved air flotation (DAF unit is evaluated. It is the objective of the present study to determine the removal efficiency of DAF in removing turbidity and organic matter from theKaroonRiverfeeding a water treatment plant. Water quality investigations over the study period revealed that, thanks to the self-purification process in the river, the Karoon water quality is acceptable with respect to total organic carbon (TOC (never exceeding 2.89 mg/l but its turbidity has great fluctuations (from as low as 42 to 1,000 NTU due to the nature of the river. Its true color is in desirable conditions. Suspended solids removal efficiency of the pilot DAF unit varied from 38% to 95%, with an average level of 72%. The results from this study indicate that DAF removal efficiency is inversely related to the volume of inflow of solids into the system so that increasing TSS decreases removal efficiency. The high turbidity level in the absence of a primary sedimentation unit causes the flotation system to lose its desired efficiency. FAD cannot be, therefore, recommended for water treatment plants fed by the Karoon water unless a pretreatment unit is used. Furthermore, as FAD's TOC removal efficiency varies by up to 82%, and since part of the organic content includes volatile organic matter causing odors and undesirable taste, FAD is recommended as a complementary process in the treatment of high quality water.

Characterization of PUD-1 and PUD-2, two proteins up-regulated in a long-lived daf-2 mutant.

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Ding, Yue-He; Du, Yun-Guang; Luo, Shukun; Li, Yu-Xin; Li, Tie-Mei; Yoshina, Sawako; Wang, Xing; Klage, Karsten; Mitani, Shohei; Ye, Keqiong; Dong, Meng-Qiu

2013-01-01

C. elegans PUD-1 and PUD-2, two proteins up-regulated in daf-2(loss-of-function) (PUD), are homologous 17-kD proteins with a large abundance increase in long-lived daf-2 mutant animals of reduced insulin signaling. In this study, we show that both PUD-1 and PUD-2 are abundantly expressed in the intestine and hypodermis, and form a heterodimer. We have solved their crystal structure to 1.9-Å resolution and found that both proteins adopt similar β-sandwich folds in the V-shaped dimer. In contrast, their homologs PUD-3, PUD-4, PUDL-1 and PUDL-2 are all monomeric proteins with distinct expression patterns in C. elegans. Thus, the PUD-1/PUD-2 heterodimer probably has a function distinct from their family members. Neither overexpression nor deletion of pud-1 and pud-2 affected the lifespan of WT or daf-2 mutant animals, suggesting that their induction in daf-2 worms does not contribute to longevity. Curiously, deletion of pud-1 and pud-2 was associated with a protective effect against paralysis induced by the amyloid β-peptide (1-42), which further enhanced the protection conferred by daf-2(RNAi) against Aβ.

DAFS study of site-specific local structure of Mn in manganese ferrite films

International Nuclear Information System (INIS)

Kravtsov, E.; Haskel, D.; Cady, A.; Yang, A.; Vittoria, C.; Zuo, X.; Harris, V.G.

2006-01-01

Manganese ferrite (MnFe 2 O 4 ) is a well-known magnetic material widely used in electronics for many years. It is well established that its magnetic behavior is strongly influenced by local structural properties of Mn ions, which are distributed between crystallographically inequivalent tetrahedral and octahedral sites in the unit cell. In order to understand and be able to tune properties of these structures, it is necessary to have detailed site-specific structural information on the system. Here we report on the application of diffraction-anomalous fine structure (DAFS) spectroscopy to resolve site-specific Mn local structures in manganese ferrite films. The DAFS measurements were done at undulator beamline 4-ID-D of the Advanced Photon Source at Argonne National Laboratory. The DAFS spectra (Fig. 1) were measured at several Bragg reflections in the vicinity of the Mn absorption K-edge, having probed separately contributions from tetrahedrally and octahedrally coordinated Mn sites. The DAFS data analysis done with an iterative Kramers-Kroenig algorithm made it possible to solve separately the local structure around different inequivalent Mn sites in the unit cell. The reliability of the data treatment was checked carefully, and it was showed that the site-specific structural parameters obtained with DAFS allow us to describe fluorescence EXAFS spectrum measured independently. Fig. 2 shows individual site contributions to the imaginary part of the resonant scattering amplitude obtained from the treatment of the data of Fig. 1. The analysis of the refined site-specific absorption spectra was done using EXAFS methods based on theoretical standards. We provided direct evidence for the tetrahedral Mn-O bond distance being increased relative to the corresponding Fe-O distance in bulk manganese ferrites. The first coordination shell number was found to be reduced significantly for Mn atoms at these sites. This finding is consistent with the well-known tendency of Mn

LC-MS Proteomics Analysis of the Insulin/IGF-1 Deficient Caenorhabditis elegans daf-2(e1370) Mutant Reveals Extensive Restructuring of Intermediary Metabolism

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Depuydt, Geert G.; Xie, Fang; Petyuk, Vladislav A.; Smolders, Arne; Brewer, Heather M.; Camp, David G.; Smith, Richard D.; Braeckman, Bart P.

2014-02-20

The insulin/IGF-1 receptor is a major known determinant of dauer formation, stress resistance, longevity and metabolism in C. elegans. In the past, whole-genome transcript profiling was used extensively to study differential gene expression in response to reduced insulin/IGF-1 signaling, including expression levels of metabolism-associated genes. Taking advantage of the recent developments in quantitative liquid chromatography mass-spectrometry (LC-MS) based proteomics, we profiled the proteomic changes that occur in response to activation of the DAF-16 transcription factor in the germline-less glp-4(bn2); daf-2(e1370) receptor mutant. Strikingly, the daf-2 profile suggests extensive reorganization of intermediary metabolism, characterized by the up-regulation of many core intermediary metabolic pathways. These include, glycolysis/gluconeogenesis, glycogenesis, pentose phosphate cycle, citric acid cycle, glyoxylate shunt, fatty acid β-oxidation, one-carbon metabolism, propionate and tyrosine catabolism, and complex I, II, III and V of the electron transport chain. Interestingly, we found simultaneous activation of reciprocally regulated metabolic pathways, which is indicative for spatio-temporal coordination of energy metabolism and/or extensive post-translational regulation of these enzymes. This restructuring of daf-2 metabolism is reminiscent to that of hypometabolic dauers, allowing the efficient and economical utilization of internal nutrient reserves, possibly also shunting metabolites through alternative energy-generating pathways, in order to sustain longevity.

LC–MS Proteomics Analysis of the Insulin/IGF-1-Deficient Caenorhabditis elegans daf-2(e1370) Mutant Reveals Extensive Restructuring of Intermediary Metabolism

Science.gov (United States)

2015-01-01

The insulin/IGF-1 receptor is a major known determinant of dauer formation, stress resistance, longevity, and metabolism in Caenorhabditis elegans. In the past, whole-genome transcript profiling was used extensively to study differential gene expression in response to reduced insulin/IGF-1 signaling, including the expression levels of metabolism-associated genes. Taking advantage of the recent developments in quantitative liquid chromatography mass spectrometry (LC–MS)-based proteomics, we profiled the proteomic changes that occur in response to activation of the DAF-16 transcription factor in the germline-less glp-4(bn2);daf-2(e1370) receptor mutant. Strikingly, the daf-2 profile suggests extensive reorganization of intermediary metabolism, characterized by the upregulation of many core intermediary metabolic pathways. These include glycolysis/gluconeogenesis, glycogenesis, pentose phosphate cycle, citric acid cycle, glyoxylate shunt, fatty acid β-oxidation, one-carbon metabolism, propionate and tyrosine catabolism, and complexes I, II, III, and V of the electron transport chain. Interestingly, we found simultaneous activation of reciprocally regulated metabolic pathways, which is indicative of spatiotemporal coordination of energy metabolism and/or extensive post-translational regulation of these enzymes. This restructuring of daf-2 metabolism is reminiscent to that of hypometabolic dauers, allowing the efficient and economical utilization of internal nutrient reserves and possibly also shunting metabolites through alternative energy-generating pathways to sustain longevity. PMID:24555535

DAF-2/insulin-like signaling in C. elegans modifies effects of dietary restriction and nutrient stress on aging, stress and growth.

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Wendy B Iser

2007-11-01

Full Text Available Dietary restriction (DR and reduced insulin/IGF-I-like signaling (IIS are two regimens that promote longevity in a variety of organisms. Genetic analysis in C. elegans nematodes has shown that DR and IIS couple to distinct cellular signaling pathways. However, it is not known whether these pathways ultimately converge on overlapping or distinct targets to extend lifespan.We investigated this question by examining additional effects of DR in wildtype animals and in daf-2 mutants with either moderate or severe IIS deficits. Surprisingly, DR and IIS had opposing effects on these physiological processes. First, DR induced a stress-related change in intestinal vesicle trafficking, termed the FIRE response, which was suppressed in daf-2 mutants. Second, DR did not strongly affect expression of a daf-2- and stress-responsive transcriptional reporter. Finally, DR-related growth impairment was suppressed in daf-2 mutants.These findings reveal that an important biological function of DAF-2/IIS is to enhance growth and survival under nutrient-limited conditions. However, we also discovered that levels of DAF-2 pathway activity modified the effects of DR on longevity. Thus, while DR and IIS clearly affect lifespan through independent targets, there may also be some prolongevity targets that are convergently regulated by these pathways.

DAF-2/insulin-like signaling in C. elegans modifies effects of dietary restriction and nutrient stress on aging, stress and growth.

Science.gov (United States)

Iser, Wendy B; Wolkow, Catherine A

2007-11-28

Dietary restriction (DR) and reduced insulin/IGF-I-like signaling (IIS) are two regimens that promote longevity in a variety of organisms. Genetic analysis in C. elegans nematodes has shown that DR and IIS couple to distinct cellular signaling pathways. However, it is not known whether these pathways ultimately converge on overlapping or distinct targets to extend lifespan. We investigated this question by examining additional effects of DR in wildtype animals and in daf-2 mutants with either moderate or severe IIS deficits. Surprisingly, DR and IIS had opposing effects on these physiological processes. First, DR induced a stress-related change in intestinal vesicle trafficking, termed the FIRE response, which was suppressed in daf-2 mutants. Second, DR did not strongly affect expression of a daf-2- and stress-responsive transcriptional reporter. Finally, DR-related growth impairment was suppressed in daf-2 mutants. These findings reveal that an important biological function of DAF-2/IIS is to enhance growth and survival under nutrient-limited conditions. However, we also discovered that levels of DAF-2 pathway activity modified the effects of DR on longevity. Thus, while DR and IIS clearly affect lifespan through independent targets, there may also be some prolongevity targets that are convergently regulated by these pathways.

Doxycyclin ameliorates a starvation-induced germline tumor in C. elegans daf-18/PTEN mutant background.

Science.gov (United States)

Wolf, Tim; Qi, Wenjing; Schindler, Verena; Runkel, Eva Diana; Baumeister, Ralf

2014-08-01

Managing available resources is a key necessity of each organism to cope with the environment. The nematode C. elegans responds to nutritional deprivation or harsh environmental conditions with a multitude of developmental adaptations, among them a starvation-induced quiescence at early larval development (L1). daf-18, the C. elegans homolog of the human tumor suppressor gene PTEN, is essential for the maintenance of survival and germline stem cell arrest during the L1 diapause. We show here that daf-18 mutants, independently to their failure to maintain G2 arrest of the primordial germ cells, develop a gonad phenotype after refeeding. This highly penetrant gonadal phenotype is further enhanced by a mutation in shc-1, encoding a protein homologous to the human adaptor ShcA. Features of this phenotype are a tumor-like phenotype encompassing hyper-proliferation of germ cell nuclei and disruption/invasion of the basement membrane surrounding the gonad. The penetrance of this phenotype is reduced by decreasing starvation temperature. In addition, it is also ameliorated in a dose-dependent way by exposure to the antibiotic doxycyclin either during starvation or during subsequent refeeding. Since, in eukaryotic cells, doxycyclin specifically blocks mitochondrial translation, our results suggest that daf-18 and shc-1;daf-18 mutants fail to adapt mitochondrial activity to reduced nutritional availability during early larval developing. Copyright © 2014 Elsevier Inc. All rights reserved.

Monascin from Monascus-Fermented Products Reduces Oxidative Stress and Amyloid-β Toxicity via DAF-16/FOXO in Caenorhabditis elegans.

Science.gov (United States)

Shi, Yeu-Ching; Pan, Tzu-Ming; Liao, Vivian Hsiu-Chuan

2016-09-28

Amyloid-β (Aβ)-induced oxidative stress and toxicity are leading risk factors for Alzheimer's disease (AD). Monascin (MS) is a novel compound proposed for antioxidative stress applications and is derived from an edible fungus secondary metabolite. This study assessed the effects of MS on oxidative stress, paralysis, Aβ accumulation, and lifespan in the nematode Caenorhabditis elegans and investigated its underlying mechanisms of action. The results showed that MS increased the survival of C. elegans under juglone-induced oxidative stress and attenuated endogenous levels of reactive oxygen species. Furthermore, MS induced a decline in Aβ-induced paralysis phenotype and Aβ deposits in the transgenic strains CL4176 and CL2006 of C. elegans, which expresses human muscle-specific Aβ1-42 in the cytoplasm of body wall muscle cells. In addition, mRNA levels of strain CL4176 of several antioxidant genes (sod-1, sod-2, sod-3, hsp16.2) and daf-16 were up-regulated by MS treatment when compared to the nontreated controls. Further evidence showed that MS treatment in C. elegans strains lacking DAF-16/FOXO did not affect paralysis or lifespan phenotypes. The findings indicate that MS reduces oxidative stress and Aβ toxicity via DAF-16 in C. elegans, suggesting that MS can be used for the prevention of AD-associated oxidative stress complications.

Waste management in the meat processing industry: Conversion of paunch and DAF sludge into solid fuel.

Science.gov (United States)

Hamawand, Ihsan; Pittaway, Pam; Lewis, Larry; Chakrabarty, Sayan; Caldwell, Justin; Eberhard, Jochen; Chakraborty, Arpita

2017-02-01

This article addresses the novel dewatering process of immersion-frying of paunch and dissolved air flotation (DAF) sludge to produce high energy pellets. Literature have been analysed to address the feasibility of replacing conventional boiler fuel at meat processing facilities with high energy paunch-DAF sludge pellets (capsules). The value proposition of pelleting and frying this mixture into energy pellets is based on a Cost-Benefit Analysis (CBA). The CBA is based on information derived from the literature and consultation with the Australian Meat Processing Industry. The calorific properties of a mixture of paunch cake solids and DAF sludge were predicted from literature and industry consultation to validate the product. This study shows that the concept of pelletizing and frying paunch is economically feasible. The complete frying and dewatering of the paunch and DAF sludge mixture produces pellets with energy content per kilogram equivalent to coal. The estimated cost of this new product is half the price of coal and the payback period is estimated to be between 1.8 and 3.2years. Further research is required for proof of concept, and to identify the technical challenges associated with integrating this technology into existing meat processing plants. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

LC–MS Proteomics Analysis of the Insulin/IGF-1-Deficient Caenorhabditis elegans daf-2(e1370) Mutant Reveals Extensive Restructuring of Intermediary Metabolism

Energy Technology Data Exchange (ETDEWEB)

Depuydt, Geert; Xie, Fang; Petyuk, Vladislav A.; Smolders, Arne; Brewer, Heather M.; Camp, David G.; Smith, Richard D.; Braeckman, Bart P.

2014-04-04

The insulin/IGF-1 receptor is a major known determinant of dauer formation, stress resistance, longevity, and metabolism in Caenorhabditis elegans. In the past, whole-genome transcript profiling was used extensively to study differential gene expression in response to reduced insulin/IGF-1 signaling, including the expression levels of metabolism-associated genes. Taking advantage of the recent developments in quantitative liquid chromatography mass spectrometry (LC–MS)-based proteomics, we profiled the proteomic changes that occur in response to activation of the DAF-16 transcription factor in the germline-less glp-4(bn2);daf-2(e1370) receptor mutant. Strikingly, the daf-2 profile suggests extensive reorganization of intermediary metabolism, characterized by the upregulation of many core intermediary metabolic pathways. These include glycolysis/gluconeogenesis, glycogenesis, pentose phosphate cycle, citric acid cycle, glyoxylate shunt, fatty acid β-oxidation, one-carbon metabolism, propionate and tyrosine catabolism, and complexes I, II, III, and V of the electron transport chain. Interestingly, we found simultaneous activation of reciprocally regulated metabolic pathways, which is indicative of spatiotemporal coordination of energy metabolism and/or extensive post-translational regulation of these enzymes. Finally, this restructuring of daf-2 metabolism is reminiscent to that of hypometabolic dauers, allowing the efficient and economical utilization of internal nutrient reserves and possibly also shunting metabolites through alternative energy-generating pathways to sustain longevity.

DAFS study of local structure of ordered nanodomains in PbMg1/3Nb2/3O3

International Nuclear Information System (INIS)

Frenkel, A.I.; Robinson, I.K.; Robinson, I.K.; Adler, D.L.; Cross, J.O.

1998-01-01

We have performed a Diffraction Anomalous Fine Structure (DAFS) study of a single crystal of the relaxor ferroelectric PbMg 1/3 Nb 2/3 O 3 . DAFS measurements were performed at the Nb K edge on a half-order Bragg reflection originating from the 1:1 ordered nanodomains. DAFS data analysis provided us with the local structure around Nb atoms in the ordered nanodomains. The Nb-O distance in the ordered region was determined to be 0.052(10) Angstrom shorter than half the lattice parameter of the bulk crystal, in good agreement with one model of the ferroelectric phase transition broadening [JETP 84, 994 (1997)]. copyright 1998 American Institute of Physics

DESIGN OF A DISSOLVED AIR FLOAT (DAF) IN THE TREATMENT OF WASTE WATER A TEXTILE

OpenAIRE

Salas Colotta, G.

2014-01-01

We presented the design of a dissolved air flotation system (DAF) to separate coagulated solids (dye) in the wastewater of a textile plant. The obtained yields of removal of suspended solids (SS) they are 82%. The size of the float to treat 35 m3/h of residual water of a textile is 5,7 m. Se presenta el diseño de un flotador por aire disuelto (DAF) para separar sólidos coagulados y floculados (tinte) provenientes de los efluentes de una planta textil. Los rendimientos obtenidos de remoción...

Muscle-Specific Histone H3K36 Dimethyltransferase SET-18 Shortens Lifespan of Caenorhabditis elegans by Repressing daf-16a Expression

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Liangping Su

2018-03-01

Full Text Available Mounting evidence shows that histone methylation, a typical epigenetic mark, is crucial for gene expression regulation during aging. Decreased trimethylation of Lys 36 on histone H3 (H3K36me3 in worms and yeast is reported to shorten lifespan. The function of H3K36me2 in aging remains unclear. In this study, we identified Caenorhabditis elegans SET-18 as a histone H3K36 dimethyltransferase. SET-18 deletion extended lifespan and increased oxidative stress resistance, dependent on daf-16 activity in the insulin/IGF pathway. In set-18 mutants, transcription of daf-16 isoform a (daf-16a was specifically upregulated. Accordingly, a decrease in H3K36me2 on daf-16a promoter was observed. Muscle-specific expression of SET-18 increased in aged worms (day 7 and day 11, attributable to elevation of global H3K36me2 and inhibition of daf-16a expression. Consequently, longevity was shortened. These findings suggested that chromatic repression mediated by tissue-specific H3K36 dimethyltransferase might be detrimental to lifespan and may have implications in human age-related diseases.

Caenorhabditis elegans DAF-2 as a Model for Human Insulin Receptoropathies

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David A. Bulger

2017-01-01

Full Text Available Human exome sequencing has dramatically increased the rate of identification of disease-associated polymorphisms. However, examining the functional consequences of those variants has created an analytic bottleneck. Insulin-like signaling in Caenorhabditis elegans has long provided a model to assess consequences of human insulin signaling mutations, but this has not been evaluated in the context of current genetic tools. We have exploited strains derived from the Million Mutation Project (MMP and gene editing to explore further the evolutionary relationships and conservation between the human and C. elegans insulin receptors. Of 40 MMP alleles analyzed in the C. elegans insulin-like receptor gene DAF-2, 35 exhibited insulin-like signaling indistinguishable from wild-type animals, indicating tolerated mutations. Five MMP alleles proved to be novel dauer-enhancing mutations, including one new allele in the previously uncharacterized C-terminus of DAF-2. CRISPR-Cas9 genome editing was used to confirm the phenotypic consequence of six of these DAF-2 mutations and to replicate an allelic series of known human disease mutations in a highly conserved tyrosine kinase active site residue, demonstrating the utility of C. elegans for directly modeling human disease. Our results illustrate the challenges associated with prediction of the phenotypic consequences of amino acid substitutions, the value of assaying mutant isoform function in vivo, and how recently developed tools and resources afford the opportunity to expand our understanding even of highly conserved regulatory modules such as insulin signaling. This approach may prove generally useful for modeling phenotypic consequences of candidate human pathogenic mutations in conserved signaling and developmental pathways.

Isoamyl alcohol odor promotes longevity and stress tolerance via DAF-16 in Caenorhabditis elegans.

Science.gov (United States)

Kurino, Chiho; Furuhashi, Tsubasa; Sudoh, Kaori; Sakamoto, Kazuichi

2017-04-01

The possibility that odor plays a role in lifespan regulation through effects on the nervous system is indicated by research on Caenorhabditis elegans. In fact, ablation of AWA and AWC, which are suggested as olfactory neurons, has been shown to extend lifespan via DAF-16, a homolog of FoxO. However, the effects of odor stimuli on the lifespan still remain unclear. Thus, we here aimed to clarify the effect of attractive and repulsive odors on longevity and stress tolerance in C. elegans and to analyze the pathways thereof. We used isoamyl alcohol as an attractive odor, and acetic acid as a repellent component, as identified by chemotaxis assay. We found that isoamyl alcohol stimulus promoted longevity in a DAF-16-dependent manner. On the other hand, acetic acid stimulus promoted thermotolerance through mechanisms independent of DAF-16. Above all, our results indicate that odor stimuli affect the lifespan and stress tolerance of C. elegans, with attractive and repulsive odors exerting their effects through different mechanisms, and that longevity is induced by both activation and inactivation of olfactory neurons. Copyright © 2017 Elsevier Inc. All rights reserved.

Two potential hookworm DAF-16 target genes, SNR-3 and LPP-1: gene structure, expression profile, and implications of a cis-regulatory element in the regulation of gene expression.

Science.gov (United States)

Gao, Xin; Goggin, Kevin; Dowling, Camille; Qian, Jason; Hawdon, John M

2015-01-08

Hookworms infect nearly 700 million people, causing anemia and developmental stunting in heavy infections. Little is known about the genomic structure or gene regulation in hookworms, although recent publication of draft genome assemblies has allowed the first investigations of these topics to be undertaken. The transcription factor DAF-16 mediates multiple developmental pathways in the free living nematode Caenorhabditis elegans, and is involved in the recovery from the developmentally arrested L3 in hookworms. Identification of downstream targets of DAF-16 will provide a better understanding of the molecular mechanism of hookworm infection. Genomic Fragment 2.23 containing a DAF-16 binding element (DBE) was used to identify overlapping complementary expressed sequence tags (ESTs). These sequences were used to search a draft assembly of the Ancylostoma caninum genome, and identified two neighboring genes, snr-3 and lpp-1, in a tail-to-tail orientation. Expression patterns of both genes during parasitic development were determined by qRT-PCR. DAF-16 dependent cis-regulatory activity of fragment 2.23 was investigated using an in vitro reporter system. The snr-3 gene spans approximately 5.6 kb in the genome and contains 3 exons and 2 introns, and contains the DBE in its 3' untranslated region. Downstream from snr-3 in a tail-to-tail arrangement is the gene lpp-1. The lpp-1 gene spans more than 6 kb and contains 10 exons and 9 introns. The A. caninum genome contains 2 apparent splice variants, but there are 7 splice variants in the A. ceylanicum genome. While the gene order is similar, the gene structures of the hookworm genes differ from their C. elegans orthologs. Both genes show peak expression in the late L4 stage. Using a cell culture based expression system, fragment 2.23 was found to have both DAF-16-dependent promoter and enhancer activity that required an intact DBE. Two putative DAF-16 targets were identified by genome wide screening for DAF-16 binding

DAF-16 and TCER-1 Facilitate Adaptation to Germline Loss by Restoring Lipid Homeostasis and Repressing Reproductive Physiology in C. elegans

Science.gov (United States)

Amrit, Francis Raj Gandhi; Steenkiste, Elizabeth Marie; Ratnappan, Ramesh; Chen, Shaw-Wen; McClendon, T. Brooke; Kostka, Dennis; Yanowitz, Judith; Olsen, Carissa Perez; Ghazi, Arjumand

2016-01-01

Elimination of the proliferating germline extends lifespan in C. elegans. This phenomenon provides a unique platform to understand how complex metazoans retain metabolic homeostasis when challenged with major physiological perturbations. Here, we demonstrate that two conserved transcription regulators essential for the longevity of germline-less adults, DAF-16/FOXO3A and TCER-1/TCERG1, concurrently enhance the expression of multiple genes involved in lipid synthesis and breakdown, and that both gene classes promote longevity. Lipidomic analyses revealed that key lipogenic processes, including de novo fatty acid synthesis, triglyceride production, desaturation and elongation, are augmented upon germline removal. Our data suggest that lipid anabolic and catabolic pathways are coordinately augmented in response to germline loss, and this metabolic shift helps preserve lipid homeostasis. DAF-16 and TCER-1 also perform essential inhibitory functions in germline-ablated animals. TCER-1 inhibits the somatic gene-expression program that facilitates reproduction and represses anti-longevity genes, whereas DAF-16 impedes ribosome biogenesis. Additionally, we discovered that TCER-1 is critical for optimal fertility in normal adults, suggesting that the protein acts as a switch supporting reproductive fitness or longevity depending on the presence or absence of the germline. Collectively, our data offer insights into how organisms adapt to changes in reproductive status, by utilizing the activating and repressive functions of transcription factors and coordinating fat production and degradation. PMID:26862916

Muscle-Specific Histone H3K36 Dimethyltransferase SET-18 Shortens Lifespan of Caenorhabditis elegans by Repressing daf-16a Expression.

Science.gov (United States)

Su, Liangping; Li, Hongyuan; Huang, Cheng; Zhao, Tingting; Zhang, Yongjun; Ba, Xueqing; Li, Zhongwei; Zhang, Yu; Huang, Baiqu; Lu, Jun; Zhao, Yanmei; Li, Xiaoxue

2018-03-06

Mounting evidence shows that histone methylation, a typical epigenetic mark, is crucial for gene expression regulation during aging. Decreased trimethylation of Lys 36 on histone H3 (H3K36me3) in worms and yeast is reported to shorten lifespan. The function of H3K36me2 in aging remains unclear. In this study, we identified Caenorhabditis elegans SET-18 as a histone H3K36 dimethyltransferase. SET-18 deletion extended lifespan and increased oxidative stress resistance, dependent on daf-16 activity in the insulin/IGF pathway. In set-18 mutants, transcription of daf-16 isoform a (daf-16a) was specifically upregulated. Accordingly, a decrease in H3K36me2 on daf-16a promoter was observed. Muscle-specific expression of SET-18 increased in aged worms (day 7 and day 11), attributable to elevation of global H3K36me2 and inhibition of daf-16a expression. Consequently, longevity was shortened. These findings suggested that chromatic repression mediated by tissue-specific H3K36 dimethyltransferase might be detrimental to lifespan and may have implications in human age-related diseases. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Emodin extends lifespan of Caenorhabditis elegans through insulin/IGF-1 signaling pathway depending on DAF-16 and SIR-2.1.

Science.gov (United States)

Zhao, Xuan; Lu, Lulu; Qi, Yonghao; Li, Miao; Zhou, Lijun

2017-10-01

The naturally occurring anthraquinone emodin has been serving primarily as an anti-bacterial and anti-inflammatory agent. However, little is known about its potential on anti-aging. This investigation examined the effect of emodin on lifespan and focused on its physiological molecular mechanisms in vivo. Using Caenorhabditis elegans (C. elegans) as an animal model, we found emodin could extend lifespan of worms and improve their antioxidant capacity. Our mechanistic studies revealed that emodin might function via insulin/IGF-1 signaling (IIS) pathway involving, specifically the core transcription factor DAF-16. Quantitative RT-PCR results illustrated that emodin up-regulated transcription of DAF-16 target genes which express antioxidants to promote antioxidant capacity and lifespan of worms. In addition, attenuated effect in sir-2.1 mutants suggests that emodin likely functioned in a SIR-2.1-dependent manner. Our study uncovers a novel role of emodin in prolonging lifespan and supports the understanding of emodin being a beneficial dietary supplement.

Caenorhabditis elegans DAF-2 as a Model for Human Insulin Receptoropathies.

Science.gov (United States)

Bulger, David A; Fukushige, Tetsunari; Yun, Sijung; Semple, Robert K; Hanover, John A; Krause, Michael W

2017-01-05

Human exome sequencing has dramatically increased the rate of identification of disease-associated polymorphisms. However, examining the functional consequences of those variants has created an analytic bottleneck. Insulin-like signaling in Caenorhabditis elegans has long provided a model to assess consequences of human insulin signaling mutations, but this has not been evaluated in the context of current genetic tools. We have exploited strains derived from the Million Mutation Project (MMP) and gene editing to explore further the evolutionary relationships and conservation between the human and C. elegans insulin receptors. Of 40 MMP alleles analyzed in the C. elegans insulin-like receptor gene DAF-2, 35 exhibited insulin-like signaling indistinguishable from wild-type animals, indicating tolerated mutations. Five MMP alleles proved to be novel dauer-enhancing mutations, including one new allele in the previously uncharacterized C-terminus of DAF-2 CRISPR-Cas9 genome editing was used to confirm the phenotypic consequence of six of these DAF-2 mutations and to replicate an allelic series of known human disease mutations in a highly conserved tyrosine kinase active site residue, demonstrating the utility of C. elegans for directly modeling human disease. Our results illustrate the challenges associated with prediction of the phenotypic consequences of amino acid substitutions, the value of assaying mutant isoform function in vivo, and how recently developed tools and resources afford the opportunity to expand our understanding even of highly conserved regulatory modules such as insulin signaling. This approach may prove generally useful for modeling phenotypic consequences of candidate human pathogenic mutations in conserved signaling and developmental pathways. Copyright © 2017 Bulger et al.

Effects of non-latching blast valves on the source term and consequences of the design-basis accidents in the Device Assembly Facility (DAF)

International Nuclear Information System (INIS)

Nguyen, D.H.

1993-08-01

The analysis of the Design-Basis Accidents (DBA) involving high explosives (HE) and Plutonium (Pu) in the assembly cell of the Device Assembly Facility (DAF), which was completed earlier, assumed latching blast valves in the ventilation system of the assembly cell. Latching valves effectively sealed a release path through the ventilation duct system. However, the blast valves in the assembly cell, as constructed are actually non-latching valves, and would reopen when the gas pressure drops to 0.5 psi above one atmosphere. Because the reopening of the blast valves provides an additional release path to the environment, and affects the material transport from the assembly cell to other DAF buildings, the DOE/NV DAF management has decided to support an additional analysis of the DAF's DBA to account for the effects of non-latching valves. Three cases were considered in the DAF's DBA, depending on the amount of HE and Pu involved, as follows: Case 1 -- 423 number-sign HE, 16 kg Pu; Case 2 -- 150 number-sign HE 10 kg Pu; Case 3 -- 55 number-sign HE 5 kg Pu. The results of the analysis with non-latching valves are summarized

Comparative metabolomics reveals endogenous ligands of DAF-12, a nuclear hormone receptor regulating C. elegans development and lifespan

Science.gov (United States)

Mahanti, Parag; Bose, Neelanjan; Bethke, Axel; Judkins, Joshua C.; Wollam, Joshua; Dumas, Kathleen J.; Zimmerman, Anna M.; Campbell, Sydney L.; Hu, Patrick J.; Antebi, Adam; Schroeder, Frank C.

2014-01-01

SUMMARY Small-molecule ligands of nuclear hormone receptors (NHRs) govern the transcriptional regulation of metazoan development, cell differentiation, and metabolism. However, the physiological ligands of many NHRs remain poorly characterized primarily due to lack of robust analytical techniques. Using comparative metabolomics, we identified endogenous steroids that act as ligands of the C. elegans NHR, DAF-12, a vitamin-D and liver-X receptor homolog regulating larval development, fat metabolism, and lifespan. The identified molecules feature unexpected chemical modifications and include only one of two DAF-12 ligands reported earlier, necessitating a revision of previously proposed ligand biosynthetic pathways. We further show that ligand profiles are regulated by a complex enzymatic network including the Rieske oxygenase DAF-36, the short-chain dehydrogenase DHS-16, and the hydroxysteroid dehydrogenase, HSD-1. Our results demonstrate the advantages of comparative metabolomics over traditional candidate-based approaches and provide a blueprint for the identification of ligands for other C. elegans and mammalian NHRs. PMID:24411940

Antioxidative Activities of Both Oleic Acid and Camellia tenuifolia Seed Oil Are Regulated by the Transcription Factor DAF-16/FOXO in Caenorhabditis elegans.

Directory of Open Access Journals (Sweden)

Chia-Cheng Wei

Full Text Available Tea seed oil is a high quality edible oil, yet lacking sufficient scientific evidences to support the nutritional and medical purposes. We identified major and minor components in Camellia tenuifolia seed oil and investigated the antioxidative activity and its underlying mechanisms in Caenorhabditis elegans.The results showed that the major constitutes in C. tenuifolia seed oil were unsaturated fatty acids (~78.4%. Moreover, two minor compounds, β-amyrin and β-sitosterol, were identified and their antioxidative activity was examined. We found that oleic acid was the major constitute in C. tenuifolia seed oil and plays a key role in the antioxidative activity of C. tenuifolia seed oil in C. elegans.This study found evidences that the transcription factor DAF-16/FOXO was involved in both oleic acid- and C. tenuifolia seed oil-mediated oxidative stress resistance in C. elegans. This study suggests the potential of C. tenuifolia seed oil as nutrient or functional foods.

Central nervous system promotes thermotolerance via FoxO/DAF-16 activation through octopamine and acetylcholine signaling in Caenorhabditis elegans.

Science.gov (United States)

Furuhashi, Tsubasa; Sakamoto, Kazuichi

2016-03-25

The autonomic nervous system (ANS) responds to many kinds of stressors to maintain homeostasis. Although the ANS is believed to regulate stress tolerance, the exact mechanism underlying this is not well understood. To understand this, we focused on longevity genes, which have functions such as lifespan extension and promotion of stress tolerance. To understand the relationship between ANS and longevity genes, we analyzed stress tolerance of Caenorhabditis elegans treated with octopamine, which has an affinity to noradrenaline in insects, and acetylcholine. Octopamine and acetylcholine did not show resistance against H2O2, but the neurotransmitters promoted thermotolerance via DAF-16. However, chronic treatment with octopamine and acetylcholine did not extend the lifespan, although DAF-16 plays an important role in longevity. In conclusion, our results show that octopamine and acetylcholine activate DAF-16 in response to stress, but chronic induction of octopamine and acetylcholine is not beneficial for increasing longevity. Copyright © 2016 Elsevier Inc. All rights reserved.

Caffeic acid phenethylester increases stress resistance and enhances lifespan in Caenorhabditis elegans by modulation of the insulin-like DAF-16 signalling pathway.

Science.gov (United States)

Havermann, Susannah; Chovolou, Yvonni; Humpf, Hans-Ulrich; Wätjen, Wim

2014-01-01

CAPE is an active constituent of propolis which is widely used in traditional medicine. This hydroxycinnamic acid derivate is a known activator of the redox-active Nrf2 signalling pathway in mammalian cells. We used C. elegans to investigate the effects of this compound on accumulation of reactive oxygen species and the modulation of the pivotal redox-active pathways SKN-1 and DAF-16 (homologues of Nrf2 and FoxO, respectively) in this model organism; these results were compared to the effects in Hct116 human colon carcinoma cells. CAPE exerts a strong antioxidative effect in C. elegans: The increase of reactive oxygen species induced by thermal stress was diminished by about 50%. CAPE caused a nuclear translocation of DAF-16, but not SKN-1. CAPE increased stress resistance of the nematode against thermal stress and finally a prolongation of the median and maximum lifespan by 9 and 17%, respectively. This increase in stress resistance and lifespan was dependent on DAF-16 as shown in experiments using a DAF-16 loss of function mutant strain. Life prolongation was retained under SKN-1 RNAi conditions showing that the effect is SKN-1 independent. The results of CAPE obtained in C. elegans differed from the results obtained in Hct116 colon carcinoma cells: CAPE also caused strong antioxidative effects in the mammalian cells, but no activation of the FoxO4 signalling pathway was detectable. Instead, an activation of the Nrf2 signalling pathway was shown by luciferase assay and western blots. CAPE activates the insulin-like DAF-16, but not the SKN-1 signalling pathway in C. elegans and therefore enhances the stress resistance and lifespan of this organism. Since modulation of the DAF-16 pathway was found to be a pivotal effect of CAPE in C. elegans, this has to be taken into account for the investigation of the molecular mechanisms of the traditional use of propolis.

Complement inhibitory proteins expression in placentas of thrombophilic women Complement inhibitory proteins expression in placentas of thrombophilic women

Directory of Open Access Journals (Sweden)

Przemysław Krzysztof Wirstlein

2012-10-01

Full Text Available Factors controlling complement activation appear to exert a protective effect on pregnancy. This is
particularly important in women with thrombophilia. The aim of this study was to determine the transcript and
protein levels of complement decay-accelerating factor (DAF and membrane cofactor protein (MCP in the
placentas of women with acquired and inherited thrombophilia. Also, we assessed immunohistochemistry staining
of inhibitors of the complement cascade, DAF and MCP proteins, in the placentas of thrombophilic women.
Placentas were collected from eight women with inherited thrombophilia and ten with acquired thrombophilia.
The levels of DAF and MCP transcripts were evaluated by qPCR, the protein level was evaluated by Western
blot. We observed a higher transcript (p < 0.05 and protein (p < 0.001 levels of DAF and MCP in the placentas
of thrombophilic women than in the control group. DAF and MCP were localized on villous syncytiotrophoblast
membranes, but the assessment of staining in all groups did not differ. The observed higher expression level of
proteins that control activation of complement control proteins is only seemingly contradictory to the changes
observed for example in the antiphospholipid syndrome. However, given the hitherto known biochemical changes
associated with thrombophilia, a mechanism in which increased expression of DAF and MCP in the placentas is
an effect of proinflammatory cytokines, which accompanies thrombophilia, is probable.Factors controlling complement activation appear to exert a protective effect on pregnancy. This is
particularly important in women with thrombophilia. The aim of this study was to determine the transcript and
protein levels of complement decay-accelerating factor (DAF and membrane cofactor protein (MCP in the
placentas of women with acquired and inherited thrombophilia. Also, we assessed immunohistochemistry

The Future of Architecture Collaborative Information Sharing: DoDAF Version 2.03 Updates

Science.gov (United States)

2012-04-30

Salamander x Select Solution Factory Select Business Solutions BPMN , UML x SimonTool Simon Labs x SimProcess CACI BPMN x System Architecture Management...for DoDAF Mega UML x Metastorm ProVision Metastorm BPMN x Naval Simulation System - 4 Aces METRON x NetViz CA x OPNET OPNET x Tool Name Vendor Primary

DAFS measurements using the image-plate Weissenberg method

International Nuclear Information System (INIS)

Sugioka, N.; Matsumoto, K.; Sasaki, S.; Tanaka, M.; Mori, T.

1998-01-01

An instrumental technique for DAFS measurements which can provide site-specific information is proposed. The approach uses (i) focusing optics with parabolic mirrors and a double-crystal monochromator, (ii) the Laue and Bragg settings and (iii) data collection by the image-plate Weissenberg method. Six image exposures are recorded per plate at five intrinsic energies and one reference energy. The single-crystal measurements were performed at the Co K-absorption edge, and the 200, 220 and 311 reflections of CoO and 511 and 911 reflections of Co 3 O 4 were used for analysis. The regression analysis of χ(k), Fourier transforms of k 3 χ(k) and back-Fourier filtering have been performed

High Energy X-Ray System Specification for the Device Assembly Facility (DAF) at the NNSS

International Nuclear Information System (INIS)

Fry, David A.

2012-01-01

This specification establishes requirements for an X-Ray System to be used at the Device Assembly Facility (DAF) at the Nevada National Security Site (NNSS) to support radiography of experimental assemblies for Laboratory (LANL, LLNL, SNL) programs conducting work at the NNSS.

Stable thermophilic anaerobic digestion of dissolved air flotation (DAF) sludge by co-digestion with swine manure.

Science.gov (United States)

Creamer, K S; Chen, Y; Williams, C M; Cheng, J J

2010-05-01

Environmentally sound treatment of by-products in a value-adding process is an ongoing challenge in animal agriculture. The sludge produced as a result of the dissolved air flotation (DAF) wastewater treatment process in swine processing facilities is one such low-value residue. The objective of this study was to determine the fundamental performance parameters for thermophilic anaerobic digestion of DAF sludge. Testing in a semi-continuous stirred tank reactor and in batch reactors was conducted to determine the kinetics of degradation and biogas yield. Stable operation could not be achieved using pure DAF sludge as a substrate, possibly due to inhibition by long-chain fatty acids or to nutrient deficiencies. However, in a 1:1 ratio (w/w, dry basis) with swine manure, operation was both stable and productive. In the semi-continuous stirred reactor at 54.5 degrees Celsius, a hydraulic residence time of 10 days, and an organic loading rate of 4.68 gVS/day/L, the methane production rate was 2.19 L/L/day and the specific methane production rate was 0.47 L/gVS (fed). Maximum specific methanogenic activity (SMA) in batch testing was 0.15 mmoles CH(4) h(-1) gVS(-1) at a substrate concentration of 6.9 gVS L(-1). Higher substrate concentrations cause an initial lag in methane production, possibly due to long-chain fatty acid or nitrogen inhibition. Copyright 2009 Elsevier Ltd. All rights reserved.

Intrinsic JNK-MAPK pathway involvement requires daf-16-mediated immune response during Shigella flexneri infection in C. elegans.

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Marudhupandiyan, Shanmugam; Balamurugan, Krishnaswamy

2017-06-01

The c-Jun N-terminal kinase-mitogen-activated protein kinase (JNK-MAPK) pathway assists in modulating signals for growth, survival, and metabolism, thereby coordinating many cellular events during normal and stress conditions. To understand the role of the JNK-MAPK pathway during bacterial infection, an in vivo model organism Caenorhabditis elegans was used. In order to check the involvement of the JNK-MAPK pathway, the survival rate of C. elegans wild type (WT), and JNK-MAPK pathway mutant worms' upon exposure to selective Gram-positive and Gram-negative pathogenic bacteria, was studied. Among the pathogens, Shigella flexneri M9OT was found to efficiently colonize inside the WT and JNK-MAPK pathway mutant worms. qPCR studies had suggested that the above pathway-specific genes kgb-2 and jnk-1 were prominently responsible for the immune response elicited by the host during the M9OT infection. In addition, daf-16, which is a major transcription factor of the insulin/insulin growth factor-1 signaling (IIS) pathway, was also found to be involved during the host response. Crosstalk between IIS and JNK-MAPK pathways has probably been involved in the activation of the host immune system, which consequently leads to lifespan extension. Furthermore, it is also observed that daf-16 activation by JNK-MAPK pathway leads to antimicrobial response, by activating lys-7 expression. These findings suggest that JNK-MAPK is not the sole pathway that enhances the immunity of the host. Nonetheless, the IIS pathway bridges the JNK-MAPK pathway that influences in protecting the host in counter to the M9OT infection.

Dafachronic acid inhibits C. elegans germ cell proliferation in a DAF-12-dependent manner.

Science.gov (United States)

Mukherjee, Madhumati; Chaudhari, Snehal N; Balachandran, Riju S; Vagasi, Alexandra S; Kipreos, Edward T

2017-12-15

Dafachronic acid (DA) is a bile acid-like steroid hormone that regulates dauer formation, heterochrony, and lifespan in C. elegans. Here, we describe that DA is an inhibitor of C. elegans germ stem cell proliferation in adult hermaphrodites. Using a C. elegans germ cell primary culture system, we show that DA inhibits the proliferation of germ cells in vitro. Exogenous DA reduces the frequency of large tumors in adult tumorous germline mutants and decreases the proliferation of wild-type germ stem cells in adult hermaphrodites. In contrast, DA has no appreciable effect on the proliferation of larval-stage germ cells in wild type. The inhibition of adult germ cell proliferation by DA requires its canonical receptor DAF-12. Blocking DA production by inactivating the cytochrome P450 DAF-9 increases germ cell proliferation in wild-type adult hermaphrodites and the frequency of large tumors in germline tumorous mutants, suggesting that DA inhibits the rate of germ cell proliferation under normal growth conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

Baseline tests of the C. H. Waterman DAF electric passenger vehicle

Science.gov (United States)

Sargent, N. B.; Maslowski, E. A.; Soltis, R. F.; Schuh, R. M.

1977-01-01

An electric vehicle was tested as part of an Energy Research Development Administration (ERDA) project to characterize the state-of-the-art of electric vehicles. The Waterman vehicle performance test results are presented in this report. The vehicle is a converted four-passenger DAF 46 sedan. It is powered by sixteen 6-volt traction batteries through a three-step contactor controller actuated by a foot throttle to change the voltage applied to the 6.7 kW motor. The braking system is a conventional hydraulic braking system.

Royal jelly promotes DAF-16-mediated proteostasis to tolerate β-amyloid toxicity in C. elegans model of Alzheimer's disease.

Science.gov (United States)

Wang, Xiaoxia; Cao, Min; Dong, Yuqing

2016-08-23

Numerous studies have demonstrated that dietary intervention may promote health and help prevent Alzheimer's disease (AD). We recently reported that bee products of royal jelly (RJ) and enzyme-treated royal jelly (eRJ) were potent to promote healthy aging in C. elegans. Here, we examined whether RJ/eRJ consumption may benefit to mitigate the AD symptom in the disease model of C. elegans. Our results showed that RJ/eRJ supplementation significantly delayed the body paralysis in AD worms, suggesting the β-amyloid (Aβ) toxicity attenuation effects of RJ/eRJ. Genetic analyses suggested that RJ/eRJ-mediated alleviation of Aβ toxicity in AD worms required DAF-16, rather than HSF-1 and SKN-1, in an insulin/IGF signaling dependent manner. Moreover, RJ/eRJ modulated the transactivity of DAF-16 and dramatically improved the protein solubility in aged worms. Given protein solubility is a hallmark of healthy proteostasis, our findings demonstrated that RJ/eRJ supplementation improved proteostasis, and this promotion depended on the transactivity of DAF-16. Collectively, the present study not only elucidated the possible anti-AD mechanism of RJ/eRJ, but also provided evidence from a practical point of view to shed light on the extensive correlation of proteostasis and the prevention of neurodegenerative disorders.

rBTI reduced β-amyloid-induced toxicity by promoting autophagy-lysosomal degradation via DAF-16 in Caenorhabditis elegans.

Science.gov (United States)

Li, Jiao; Cui, Xiaodong; Ma, Xiaoli; Wang, Zhuanhua

2017-03-01

Alzheimer's disease (AD) is an age-related neurodegenerative disease, of which β-amyloid (Aβ) induced toxicity was suggested as a main cause. Some substances with prolongevity effects have been shown to be protective against AD. In a previous study we demonstrated that a recombinant buckwheat trypsin inhibitor (rBTI) could prolonge the lifespan in Caenorhabditis elegans (C. elegans). Here, we investigated whether rBTI may benefit to mitigate the AD symptom by feeding the AD model C. elegans CL4176. CL4176 is a transgenic C. elegans expressing human Aβ 3-42 in muscle tissue. The results showed that rBTI not only could extend lifespan but also could reduce Aβ toxicity-triggered body paralysis in AD worms. Further study found the accumulation of Aβ was decreased and autophagy-lysosomal degradation pathway was activated in AD worms treated with rBTI. Moreover, the inhibition of autophagy reduced rBTI-mediated paralysis delay. Genetic analyses showed rBTI increased the transcriptional activity of dauer formation abnormal-16 (DAF-16) and the disruption of daf-16 abolished rBTI-mediated protective effect in AD worms. Taken together, these data indicated that rBTI promoted the autophagy-lysosomal degradation pathway to reduce the Aβ-induced toxicity via DAF-16 in an AD model C. elegans, implying that BTI has the potential to protect against AD. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparison between XAS, AWAXS and DAFS applied to nanometer scale supported metallic clusters. Pt.1; monometallic clusters

International Nuclear Information System (INIS)

Bazin, D.C.; Sayers, D.A.

1993-01-01

The structural information found using three techniques related to synchrotron radiation are compared. XAS (X-ray Absorption Spectroscopy), AWAXS (Anomalous Wide Angle X-ray Scattering) and DAFS (Diffraction Anomalous Fine Structure) are applied to nanometer scale metallic clusters. (author)

FOXO/DAF-16 Activation Slows Down Turnover of the Majority of Proteins in C. elegans

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Ineke Dhondt

2016-09-01

Full Text Available Most aging hypotheses assume the accumulation of damage, resulting in gradual physiological decline and, ultimately, death. Avoiding protein damage accumulation by enhanced turnover should slow down the aging process and extend the lifespan. However, lowering translational efficiency extends rather than shortens the lifespan in C. elegans. We studied turnover of individual proteins in the long-lived daf-2 mutant by combining SILeNCe (stable isotope labeling by nitrogen in Caenorhabditis elegans and mass spectrometry. Intriguingly, the majority of proteins displayed prolonged half-lives in daf-2, whereas others remained unchanged, signifying that longevity is not supported by high protein turnover. This slowdown was most prominent for translation-related and mitochondrial proteins. In contrast, the high turnover of lysosomal hydrolases and very low turnover of cytoskeletal proteins remained largely unchanged. The slowdown of protein dynamics and decreased abundance of the translational machinery may point to the importance of anabolic attenuation in lifespan extension, as suggested by the hyperfunction theory.

Calculation of coupling factor for double-period accelerating structure

International Nuclear Information System (INIS)

Bian Xiaohao; Chen Huaibi; Zheng Shuxin

2005-01-01

In the design of the linear accelerating structure, the coupling factor between cavities is a crucial parameter. The error of coupling factor accounts for the electric or magnetic field error mainly. To accurately design the coupling iris, the accurate calculation of coupling factor is essential. The numerical simulation is widely used to calculate the coupling factor now. By using MAFIA code, two methods have been applied to calculate the dispersion characteristics of the single-period structure, one method is to simulate the traveling wave mode by the period boundary condition; another method is to simulate the standing wave mode by the electrical boundary condition. In this work, the authors develop the two methods to calculate the coupling factor of double-period accelerating structure. Compared to experiment, the results for both methods are very similar, and in agreement with measurement within 15% deviation. (authors)

Up-regulation of intestinal vascular endothelial growth factor by Afa/Dr diffusely adhering Escherichia coli.

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Gaëlle Cane

Full Text Available BACKGROUND: Angiogenesis has been recently described as a novel component of inflammatory bowel disease pathogenesis. The level of vascular endothelial growth factor (VEGF has been found increased in Crohn's disease and ulcerative colitis mucosa. To question whether a pro-inflammatory Escherichia coli could regulate the expression of VEGF in human intestinal epithelial cells, we examine the response of cultured human colonic T84 cells to infection by E. coli strain C1845 that belongs to the typical Afa/Dr diffusely adhering E. coli family (Afa/Dr DAEC. METHODOLOGY: VEGF mRNA expression was examined by Northern blotting and q-PCR. VEGF protein levels were assayed by ELISA and its bioactivity was analysed in endothelial cells. The bacterial factor involved in VEGF induction was identified using recombinant E. coli expressing Dr adhesin, purified Dr adhesin and lipopolysaccharide. The signaling pathway activated for the up-regulation of VEGF was identified using a blocking monoclonal anti-DAF antibody, Western blot analysis and specific pharmacological inhibitors. PRINCIPAL FINDINGS: C1845 bacteria induce the production of VEGF protein which is bioactive. VEGF is induced by adhering C1845 in both a time- and bacteria concentration-dependent manner. This phenomenon is not cell line dependent since we reproduced this observation in intestinal LS174, Caco2/TC7 and INT407 cells. Up-regulation of VEGF production requires: (1 the interaction of the bacterial F1845 adhesin with the brush border-associated decay accelerating factor (DAF, CD55 acting as a bacterial receptor, and (2 the activation of a Src protein kinase upstream of the activation of the Erk and Akt signaling pathways. CONCLUSIONS: Results demonstrate that a Afa/Dr DAEC strain induces an adhesin-dependent activation of DAF signaling that leads to the up-regulation of bioactive VEGF in cultured human intestinal cells. Thus, these results suggest a link between an entero-adherent, pro

Comparison between XAS, AWAXS and DAFS applied to nanometer scale supported metallic clusters. Pt.2; bimetallic clusters

International Nuclear Information System (INIS)

Bazin, D.; Sayers, D.

1993-01-01

The structural information obtained using three techniques related to synchrotron radiation are compared. XAS (X-ray Absorption Spectroscopy), AWAXS (Anomalous Wide Angle X-ray Scattering) and DAFS (Diffraction Anomalous Fine Structure) are applied to the study of nanometer scale bimetallic clusters. (author)

Morphogenesis of Strongyloides stercoralis infective larvae requires the DAF-16 ortholog FKTF-1.

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Michelle L Castelletto

2009-04-01

Full Text Available Based on metabolic and morphological similarities between infective third-stage larvae of parasitic nematodes and dauer larvae of Caenorhabditis elegans, it is hypothesized that similar genetic mechanisms control the development of these forms. In the parasite Strongyloides stercoralis, FKTF-1 is an ortholog of DAF-16, a forkhead transcription factor that regulates dauer larval development in C. elegans. Using transgenesis, we investigated the role of FKTF-1 in S. stercoralis' infective larval development. In first-stage larvae, GFP-tagged recombinant FKTF-1b localizes to the pharynx and hypodermis, tissues remodeled in infective larvae. Activating and inactivating mutations at predicted AKT phosphorylation sites on FKTF-1b give constitutive cytoplasmic and nuclear localization of the protein, respectively, indicating that its post-translational regulation is similar to other FOXO-class transcription factors. Mutant constructs designed to interfere with endogenous FKTF-1b function altered the intestinal and pharyngeal development of the larvae and resulted in some transgenic larvae failing to arrest in the infective stage. Our findings indicate that FKTF-1b is required for proper morphogenesis of S. stercoralis infective larvae and support the overall hypothesis of similar regulation of dauer development in C. elegans and the formation of infective larvae in parasitic nematodes.

FOXO/DAF-16 Activation Slows Down Turnover of the Majority of Proteins in C. elegans.

Science.gov (United States)

Dhondt, Ineke; Petyuk, Vladislav A; Cai, Huaihan; Vandemeulebroucke, Lieselot; Vierstraete, Andy; Smith, Richard D; Depuydt, Geert; Braeckman, Bart P

2016-09-13

Most aging hypotheses assume the accumulation of damage, resulting in gradual physiological decline and, ultimately, death. Avoiding protein damage accumulation by enhanced turnover should slow down the aging process and extend the lifespan. However, lowering translational efficiency extends rather than shortens the lifespan in C. elegans. We studied turnover of individual proteins in the long-lived daf-2 mutant by combining SILeNCe (stable isotope labeling by nitrogen in Caenorhabditiselegans) and mass spectrometry. Intriguingly, the majority of proteins displayed prolonged half-lives in daf-2, whereas others remained unchanged, signifying that longevity is not supported by high protein turnover. This slowdown was most prominent for translation-related and mitochondrial proteins. In contrast, the high turnover of lysosomal hydrolases and very low turnover of cytoskeletal proteins remained largely unchanged. The slowdown of protein dynamics and decreased abundance of the translational machinery may point to the importance of anabolic attenuation in lifespan extension, as suggested by the hyperfunction theory. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Calculation of coupling factor for the heterogeneous accelerating structure

International Nuclear Information System (INIS)

Bian Xiaohao; Chen Huaibi; Zheng Shuxin

2006-01-01

The converging part of electron accelerator is designed to converge the phase of injecting electrons, improving the beam quality of the accelerator. It is very crucial to calculate the coupling factor between cavities and to design the geometry structure of the coupling irises. By the E module of code MAFIA, the authors calculate the frequency of every single resonant cavity and the two eigenfrequencies of two-cavitiy line. Then we get the coupling factor between the two cavities. This method can be used to design the geometry structure of the coupling isises between every two cavities. Compared to experiment, the results of the method is very accurate. (authors)

Optimization of the factors that accelerate leaching

International Nuclear Information System (INIS)

Fuhrmann, M.; Pietrzak, R.F.; Franz, E.M.; Heiser, J.H. III; Colombo, P.

1989-03-01

The prediction of long-term leachability of low-level radioactive waste forms is an essential element of disposal-site performance assessment. This report describes experiments and modeling techniques used to develop an accelerated leach test that meets this need. The acceleration in leaching rates caused by the combinations of two or more factors were experimentally determined. These factors were identified earlier as being able to individually accelerate leaching. They are: elevated temperature, the size of the waste form, the ratio of the volume of leachant to the surface area of the waste form, and the frequency of replacement of the leachant. The solidification agents employed were ones that are currently used to treat low-level radioactive wastes, namely portland type I cement, bitumen, and vinyl ester-styrene. The simulated wastes, sodium sulfate, sodium tetraborate, and incinerator ash, are simplified representatives of typical low-level waste streams. Experiments determined the leaching behavior of the radionuclides of cesium (Cs-137), strontium (Sr-85), and cobalt (Co-60 or Co-57) from several different formulations of solidification agents and waste types. Leaching results were based upon radiochemical and elemental analyses of aliquots of the leachate, and on its total alkalinity and pH at various times during the experiment (up to 120 days). Solid phase analyses were carried out by Scanning/Electron Microscopy and Energy Dispersive Spectroscopy on the waste forms before and after some leaching experiments. 43 refs., 96 figs., 16 tabs

Determination of accelerated factors in gradient descent iterations based on Taylor's series

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Petrović Milena

2017-01-01

Full Text Available In this paper the efficiency of accelerated gradient descent methods regarding the way of determination of accelerated factor is considered. Due to the previous researches we assert that the use of Taylor's series of posed gradient descent iteration in calculation of accelerated parameter gives better final results than some other choices. We give a comparative analysis of efficiency of several methods with different approaches in obtaining accelerated parameter. According to the achieved results of numerical experiments we make a conclusion about the one of the most optimal way in defining accelerated parameter in accelerated gradient descent schemes.

Criticality Safety Evaluation for the TACS at DAF

Energy Technology Data Exchange (ETDEWEB)

Percher, C. M. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Heinrichs, D. P. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

2011-06-10

Hands-on experimental training in the physical behavior of multiplying systems is one of ten key areas of training required for practitioners to become qualified in the discipline of criticality safety as identified in DOE-STD-1135-99, Guidance for Nuclear Criticality Safety Engineer Training and Qualification. This document is a criticality safety evaluation of the training activities and operations associated with HS-3201-P, Nuclear Criticality 4-Day Training Course (Practical). This course was designed to also address the training needs of nuclear criticality safety professionals under the auspices of the NNSA Nuclear Criticality Safety Program1. The hands-on, or laboratory, portion of the course will utilize the Training Assembly for Criticality Safety (TACS) and will be conducted in the Device Assembly Facility (DAF) at the Nevada Nuclear Security Site (NNSS). The training activities will be conducted by Lawrence Livermore National Laboratory following the requirements of an Integrated Work Sheet (IWS) and associated Safety Plan. Students will be allowed to handle the fissile material under the supervision of an LLNL Certified Fissile Material Handler.

Using weigh-in-motion data to determine bridge dynamic amplification factor

Directory of Open Access Journals (Sweden)

Kalin Jan

2015-01-01

Full Text Available The dynamic component of bridge traffic loading is commonly taken into account with a Dynamic Amplification Factor (DAF – the ratio between the maximum dynamic and static load effects on a bridge. In the design codes, this factor is generally higher than in reality. While this is fine for new bridges that must account for various risks during their life-time, it imposes unnecessary conservativism into assessment of the existing well defined bridges. Therefore, analysis of existing bridges should apply more realistic DAF values. One way of obtaining them experimentally is by bridge weigh-in-motion (B-WIM measurements, which use an existing instrumented bridge or culvert to weigh all crossing vehicles at highway speeds. The B-WIM system had been equipped with two methods of obtaining an approximation to the static response of the. The first method uses the sum of influence lines. This method relies on accurate axle identification, the failure of which can have a large influence on the DAF value. The other method uses a pre-determined low-pass filter to remove the dynamic component of the measured signal; however an expert is needed to set the filter parameters. A new approach that tries to eliminate these two drawbacks has been developed. In this approach the parameters for the filter are determined automatically by fitting the filtered response to the sum of the influence lines. The measurement of DAF on a typical bridge site agrees with experiments performed in the ARCHES [1] project: dynamic amplification decreases as static loading increases.

Neuronal migration is regulated by endogenous RNAi and chromatin-binding factor ZFP-1/AF10 in Caenorhabditis elegans.

Science.gov (United States)

Kennedy, Lisa M; Grishok, Alla

2014-05-01

Endogenous short RNAs and the conserved plant homeodomain (PHD) zinc-finger protein ZFP-1/AF10 regulate overlapping sets of genes in Caenorhabditis elegans, which suggests that they control common biological pathways. We have shown recently that the RNAi factor RDE-4 and ZFP-1 negatively modulate transcription of the insulin/PI3 signaling-dependent kinase PDK-1 to promote C. elegans fitness. Moreover, we have demonstrated that the insulin/IGF-1-PI3K-signaling pathway regulates the activity of the DAF-16/FOXO transcription factor in the hypodermis to nonautonomously promote the anterior migrations of the hermaphrodite-specific neurons (HSNs) during embryogenesis of C. elegans. In this study, we implicate the PHD-containing isoform of ZFP-1 and endogenous RNAi in the regulation of HSN migration. ZFP-1 affects HSN migration in part through its negative effect on pdk-1 transcription and modulation of downstream DAF-16 activity. We also identify a novel role for ZFP-1 and RNAi pathway components, including RDE-4, in the regulation of HSN migration in parallel with DAF-16. Therefore, the coordinated activities of DAF-16, ZFP-1, and endogenous RNAi contribute to gene regulation during development to ensure proper neuronal positioning.

The Story of Serum Prothrombin Conversion Accelerator, Proconvertin, Stable Factor, Cothromboplastin, Prothrombin Accelerator or Autoprothrombin I, and Their Subsequent Merging into Factor VII.

Science.gov (United States)

Girolami, Antonio; Cosi, Elisabetta; Santarossa, Claudia; Ferrari, Silvia; Luigia Randi, Maria

2015-06-01

Factor VII (FVII) deficiency is one of the two congenital coagulation disorders that was not discovered by the description of a new bleeding patient whose clotting pattern did not fit the blood coagulation knowledge of the time (the other is factor XIII deficiency). The existence of an additional factor capable of accelerating the conversion of prothrombin into thrombin was suspected before 1951, the year in which the first family with FVII deficiency was discovered. As several investigators were involved in the discovery of FVII deficiency from both sides of the Atlantic, several different names were tentatively suggested to define this entity, namely stable factor (in contrast with labile factor or FV), cothromboplastin, proconvertin, serum prothrombin conversion accelerator, prothrombin acceleration, and autoprothrombin I. The last term was proposed by those who denied the existence of this new entity, which was instead considered to be a derivate of prothrombin activation, namely autoprothrombin. The description of several families, from all over the world, of the same defect, however clearly demonstrated the singularity of the condition. Factor VII was then proposed to define this protein. In subsequent years, several variants were described with peculiar reactivity toward tissue thromboplastins of different origin. Molecular biology techniques demonstrated several gene mutations, usually missense mutations, often involving exon 8 of the FVII gene. Later studies dealt with the relation of FVII with tissue factor and activated FVII (FVIIa). The evaluation of circulating FVIIa was made possible by the use of a truncated form of tissue factor, which is only sensitive to FVIIa present in the circulation. The development of FVII concentrates, both plasma derived and recombinant, has facilitated therapeutic management of FVII-deficient patients. The use of FVIIa concentrates was noted to be associated with the occasional occurrence of thrombotic events, mainly

Acceleration of wound healing with stem cell-derived growth factors.

Science.gov (United States)

Tamari, Masayuki; Nishino, Yudai; Yamamoto, Noriyuki; Ueda, Minoru

2013-01-01

Recently, it has been revealed that bone marrow-derived mesenchymal stem cells (MSCs) accelerate the healing of skin wounds. Although the proliferative capacity of MSCs decreases with age, MSCs secrete many growth factors. The present study examined the effect of mesenchymal stem cell-conditioned medium (MSC-CM) on wound healing. The wound-healing process was observed macroscopically and histologically using an excisional wound-splinting mouse model, and the expression level of hyaluronic acid related to the wound healing process was observed to evaluate the wound-healing effects of MSC, MSC-CM, and control (phosphate-buffered saline). The MSC and MSC-CM treatments accelerated wound healing versus the control group. At 7 days after administration, epithelialization was accelerated, thick connective tissue had formed in the skin defect area, and the wound area was reduced in the MSC and MSC-CM groups versus the control group. At 14 days, infiltration of inflammatory cells was decreased versus 7 days, and the wounds were closed in the MSC and MSC-CM groups, while a portion of epithelium was observed in the control group. At 7 and 14 days, the MSC and MSC-CM groups expressed significantly higher levels of hyaluronic acid versus the control group (P wound healing versus the control group to a similar degree. Accordingly, it is suggested that the MSC-CM contains growth factor derived from stem cells, is able to accelerate wound healing as well as stem cell transplantation, and may become a new therapeutic method for wound healing in the future.

A transcription elongation factor that links signals from the reproductive system to lifespan extension in Caenorhabditis elegans.

Directory of Open Access Journals (Sweden)

Arjumand Ghazi

2009-09-01

Full Text Available In Caenorhabditis elegans and Drosophila melanogaster, the aging of the soma is influenced by the germline. When germline-stem cells are removed, aging slows and lifespan is increased. The mechanism by which somatic tissues respond to loss of the germline is not well-understood. Surprisingly, we have found that a predicted transcription elongation factor, TCER-1, plays a key role in this process. TCER-1 is required for loss of the germ cells to increase C. elegans' lifespan, and it acts as a regulatory switch in the pathway. When the germ cells are removed, the levels of TCER-1 rise in somatic tissues. This increase is sufficient to trigger key downstream events, as overexpression of tcer-1 extends the lifespan of normal animals that have an intact reproductive system. Our findings suggest that TCER-1 extends lifespan by promoting the expression of a set of genes regulated by the conserved, life-extending transcription factor DAF-16/FOXO. Interestingly, TCER-1 is not required for DAF-16/FOXO to extend lifespan in animals with reduced insulin/IGF-1 signaling. Thus, TCER-1 specifically links the activity of a broadly deployed transcription factor, DAF-16/FOXO, to longevity signals from reproductive tissues.

Diosgenin a phytosterol substitute for cholesterol, prolongs the lifespan and mitigates glucose toxicity via DAF-16/FOXO and GST-4 in Caenorhabditis elegans.

Science.gov (United States)

Shanmugam, Govindan; Mohankumar, Amirthalingam; Kalaiselvi, Duraisamy; Nivitha, Sundararaj; Murugesh, Easwaran; Shanmughavel, Piramanayagam; Sundararaj, Palanisamy

2017-11-01

Caenorhabditis elegans is a sterol auxotroph requires minute amount of exogenous sterol for their growth and development. To culture the C. elegans, cholesterol was given as sterol molecule to maintain the optimum survival of worms. Diosgenin (DG), a plant derived steroidal saponin, structurally similar to cholesterol has been used as a precursor for the synthesis of steroidal hormones. In this study, worms were cultured with cholesterol (Cho + ) and cholesterol-free (Cho - ) medium with DG (5, 10 and 50μg/mL) at 20°C. It was observed that worms cultured in (Cho - ) exhibits late egg production, reduced lipid level and short lifespan, while addition of DG overcomes all defective facts. Combinations of both cholesterol and DG further extend the lifespan (20.8%), hinder lipid level and resistance to oxidative, thermal and high glucose stress. The intracellular ROS quantification was done by flouroscenic probe H2DCF-DA and confirmed that DG had significantly reduced ROS level (35.85%). Increased lifespan of worms were observed in the medium treated with DG which activates the nuclear translocation of DAF-16/FOXO transcription factor, followed by downstream antioxidant gene sod-3 as evidenced by GFP tagged strain. The expression of Phase II detoxification enzyme GST-4 significantly (pdaf-16, skn-1, and eat-2. These studies have proved that DG is a sterol source to worms and modulate the DAF-16, SOD-3 and GST-4 expression levels to extend the lifespan of worms. The present study has also highlighted the use of phytosterols as an alternative to cholesterol. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

A conserved neuronal DAF-16/FoxO plays an important role in conveying pheromone signals to elicit repulsion behavior in Caenorhabditis elegans.

Science.gov (United States)

Park, Donha; Hahm, Jeong-Hoon; Park, Saeram; Ha, Go; Chang, Gyeong-Eon; Jeong, Haelim; Kim, Heekyeong; Kim, Sunhee; Cheong, Eunji; Paik, Young-Ki

2017-08-03

Animals use pheromones as a conspecific chemical language to respond appropriately to environmental changes. The soil nematode Caenorhabditis elegans secretes ascaroside pheromones throughout the lifecycle, which influences entry into dauer phase in early larvae, in addition to sexual attraction and aggregation. In adult hermaphrodites, pheromone sensory signals perceived by worms usually elicit repulsion as an initial behavioral signature. However, the molecular mechanisms underlying neuronal pheromone sensory process from perception to repulsion in adult hermaphrodites remain poorly understood. Here, we show that pheromone signals perceived by GPA-3 is conveyed through glutamatergic neurotransmission in which neuronal DAF-16/FoxO plays an important modulatory role by controlling glutaminase gene expression. We further provide evidence that this modulatory role for DAF-16/FoxO seems to be conserved evolutionarily by electro-physiological study in mouse primary hippocampal neurons that are responsible for glutamatergic neurotransmission. These findings provide the basis for understanding the nematode pheromone signaling, which seems crucial for adaptation of adult hermaphrodites to changes in environmental condition for survival.

Mechanisms of evasion of Schistosoma mansoni schistosomula to the lethal activity of complement

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F. Juarez Ramalho-Pinto

1992-01-01

Full Text Available Schistosomula of Schistosoma mansoni became resistant to antibody-dependent complement damage in vitro after pre-incubation with normal human erythrocytes (NHuE whatever the ABO or Rh blood group. Resistant parasites were shown to acquire host decay accelerating factor (DAF , a 70 kDa glycoprotein attached to the membrane of NHue by a GPI anchor. IgG2a mAb anti-human DAF (IA10 immunoprecipitated a 70 kDa molecule from 125I-labeled schistosomula pre-incubated with NHuE and inhibited their resistance to complement-dependent killing in vtro. Incubationof schistosomula with erytrocytes from patients with paroxsimal nocturnal hemoglobinuria (PNHE or SRBC, wich are DAF-deficient, did not protect the parasites from complement lesion. Supernatant of 100,000 x g collected from NHuE incubated for 24 h in defined medium was shown to contain a soluble form of DAF and to protect schistosomula from complement killing. Schistosomula treated with trypsin before incubation with NHuE ghosts did not become resistant to complement damage. On the other hand, pre-treatment with chymotrypsin did not interfere with the acquisition of resistance by the schistosomula. These results indicate that, in vitro, NHuE DAF can be transferred to schistosomula in a soluble form and that the binding of this molecule to the parasite surface is dependent upon trypsin-sensitive chymotrypsin-insensitive polipeptide(s present on the surface of the worm.

DAF-18/PTEN signals through AAK-1/AMPK to inhibit MPK-1/MAPK in feedback control of germline stem cell proliferation.

Directory of Open Access Journals (Sweden)

Patrick Narbonne

2017-04-01

Full Text Available Under replete growth conditions, abundant nutrient uptake leads to the systemic activation of insulin/IGF-1 signalling (IIS and the promotion of stem cell growth/proliferation. Activated IIS can stimulate the ERK/MAPK pathway, the activation of which also supports optimal stem cell proliferation in various systems. Stem cell proliferation rates can further be locally refined to meet the resident tissue's need for differentiated progeny. We have recently shown that the accumulation of mature oocytes in the C. elegans germ line, through DAF-18/PTEN, inhibits adult germline stem cell (GSC proliferation, despite high systemic IIS activation. We show here that this feedback occurs through a novel cryptic signalling pathway that requires PAR-4/LKB1, AAK-1/AMPK and PAR-5/14-3-3 to inhibit the activity of MPK-1/MAPK, antagonize IIS, and inhibit both GSC proliferation and the production of additional oocytes. Interestingly, our results imply that DAF-18/PTEN, through PAR-4/LKB1, can activate AAK-1/AMPK in the absence of apparent energy stress. As all components are conserved, similar signalling cascades may regulate stem cell activities in other organisms and be widely implicated in cancer.

DAF: differential ACE filtering image quality assessment by automatic color equalization

Science.gov (United States)

Ouni, S.; Chambah, M.; Saint-Jean, C.; Rizzi, A.

2008-01-01

Ideally, a quality assessment system would perceive and measure image or video impairments just like a human being. But in reality, objective quality metrics do not necessarily correlate well with perceived quality [1]. Plus, some measures assume that there exists a reference in the form of an "original" to compare to, which prevents their usage in digital restoration field, where often there is no reference to compare to. That is why subjective evaluation is the most used and most efficient approach up to now. But subjective assessment is expensive, time consuming and does not respond, hence, to the economic requirements [2,3]. Thus, reliable automatic methods for visual quality assessment are needed in the field of digital film restoration. The ACE method, for Automatic Color Equalization [4,6], is an algorithm for digital images unsupervised enhancement. It is based on a new computational approach that tries to model the perceptual response of our vision system merging the Gray World and White Patch equalization mechanisms in a global and local way. Like our vision system ACE is able to adapt to widely varying lighting conditions, and to extract visual information from the environment efficaciously. Moreover ACE can be run in an unsupervised manner. Hence it is very useful as a digital film restoration tool since no a priori information is available. In this paper we deepen the investigation of using the ACE algorithm as a basis for a reference free image quality evaluation. This new metric called DAF for Differential ACE Filtering [7] is an objective quality measure that can be used in several image restoration and image quality assessment systems. In this paper, we compare on different image databases, the results obtained with DAF and with some subjective image quality assessments (Mean Opinion Score MOS as measure of perceived image quality). We study also the correlation between objective measure and MOS. In our experiments, we have used for the first image

Social-emotional characteristics of gifted accelerated and non-accelerated students in the Netherlands.

Science.gov (United States)

Hoogeveen, Lianne; van Hell, Janet G; Verhoeven, Ludo

2012-12-01

In the studies of acceleration conducted so far a multidimensional perspective has largely been neglected. No attempt has been made to relate social-emotional characteristics of accelerated versus non-accelerated students in perspective of environmental factors. In this study, social-emotional characteristics of accelerated gifted students in the Netherlands were examined in relation to personal and environmental factors. Self-concept and social contacts of accelerated (n = 148) and non-accelerated (n = 55) gifted students, aged 4 to 27 (M = 11.22, SD = 4.27) were measured. Self-concept and social contacts of accelerated and non-accelerated gifted students were measured using a questionnaire and a diary, and parents of these students evaluated their behavioural characteristics. Gender and birth order were studied as personal factors and grade, classroom, teachers' gender, teaching experience, and the quality of parent-school contact as environmental factors. The results showed minimal differences in the social-emotional characteristics of accelerated and non-accelerated gifted students. The few differences we found favoured the accelerated students. We also found that multiple grade skipping does not have negative effects on social-emotional characteristics, and that long-term effects of acceleration tend to be positive. As regards the possible modulation of personal and environmental factors, we merely found an impact of such factors in the non-accelerated group. The results of this study strongly suggest that social-emotional characteristics of accelerated gifted students and non-accelerated gifted students are largely similar. These results thus do not support worries expressed by teachers about the acceleration of gifted students. Our findings parallel the outcomes of earlier studies in the United States and Germany in that we observed that acceleration does not harm gifted students, not even in the case of multiple grade skipping. On the contrary, there is a

The GATA transcription factor egl-27 delays aging by promoting stress resistance in Caenorhabditis elegans.

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Xiao Xu

Full Text Available Stress is a fundamental aspect of aging, as accumulated damage from a lifetime of stress can limit lifespan and protective responses to stress can extend lifespan. In this study, we identify a conserved Caenorhabditis elegans GATA transcription factor, egl-27, that is involved in several stress responses and aging. We found that overexpression of egl-27 extends the lifespan of wild-type animals. Furthermore, egl-27 is required for the pro-longevity effects from impaired insulin/IGF-1 like signaling (IIS, as reduced egl-27 activity fully suppresses the longevity of worms that are mutant for the IIS receptor, daf-2. egl-27 expression is inhibited by daf-2 and activated by pro-longevity factors daf-16/FOXO and elt-3/GATA, suggesting that egl-27 acts at the intersection of IIS and GATA pathways to extend lifespan. Consistent with its role in IIS signaling, we found that egl-27 is involved in stress response pathways. egl-27 expression is induced in the presence of multiple stresses, its targets are significantly enriched for many types of stress genes, and altering levels of egl-27 itself affects survival to heat and oxidative stress. Finally, we found that egl-27 expression increases between young and old animals, suggesting that increased levels of egl-27 in aged animals may act to promote stress resistance. These results identify egl-27 as a novel factor that links stress and aging pathways.

A new addition to the Phillipsite family of molecular sieves: A divalent metal-ion-framework substituted microporous aluminophosphate (DAF-8)

Science.gov (United States)

Barrett, Philip A.; Sankar, Gopinathan; Stephenson, Richard; Catlow, C. Richard A.; Thomas, John Meurig; Jones, Richard H.; Teat, Simon J.

2006-03-01

By adding substantial amounts of either Co(II) or Zn(II) salts to a gel composed of Al 2O 3, P 2O 5 and the organic template 1,4-diaminocyclohexane, the tendency to yield layered aluminophosphates (AlPOs) is tilted in favour of the production of three-dimensional microporous MAlPOs: in particular, phase-pure samples of a novel Phillipsite structure (designated Davy-Faraday number 8, DAF-8) are formed.

Inertial attitude control of a bat-like morphing-wing air vehicle

International Nuclear Information System (INIS)

Colorado, J; Barrientos, A; Rossi, C; Parra, C

2013-01-01

This paper presents a novel bat-like unmanned aerial vehicle inspired by the morphing-wing mechanism of bats. The goal of this paper is twofold. Firstly, a modelling framework is introduced for analysing how the robot should manoeuvre by means of changing wing morphology. This allows the definition of requirements for achieving forward and turning flight according to the kinematics of the wing modulation. Secondly, an attitude controller named backstepping+DAF is proposed. Motivated by biological evidence about the influence of wing inertia on the production of body accelerations, the attitude control law incorporates wing inertia information to produce desired roll (φ) and pitch (θ) acceleration commands (desired angular acceleration function (DAF)). This novel control approach is aimed at incrementing net body forces (F net ) that generate propulsion. Simulations and wind-tunnel experimental results have shown an increase of about 23% in net body force production during the wingbeat cycle when the wings are modulated using the DAF as a part of the backstepping control law. Results also confirm accurate attitude tracking in spite of high external disturbances generated by aerodynamic loads at airspeeds up to 5 ms −1 . (paper)

Inertial attitude control of a bat-like morphing-wing air vehicle.

Science.gov (United States)

Colorado, J; Barrientos, A; Rossi, C; Parra, C

2013-03-01

This paper presents a novel bat-like unmanned aerial vehicle inspired by the morphing-wing mechanism of bats. The goal of this paper is twofold. Firstly, a modelling framework is introduced for analysing how the robot should manoeuvre by means of changing wing morphology. This allows the definition of requirements for achieving forward and turning flight according to the kinematics of the wing modulation. Secondly, an attitude controller named backstepping+DAF is proposed. Motivated by biological evidence about the influence of wing inertia on the production of body accelerations, the attitude control law incorporates wing inertia information to produce desired roll (ϕ) and pitch (θ) acceleration commands (desired angular acceleration function (DAF)). This novel control approach is aimed at incrementing net body forces (F(net)) that generate propulsion. Simulations and wind-tunnel experimental results have shown an increase of about 23% in net body force production during the wingbeat cycle when the wings are modulated using the DAF as a part of the backstepping control law. Results also confirm accurate attitude tracking in spite of high external disturbances generated by aerodynamic loads at airspeeds up to 5 ms⁻¹.

Radiation pressure acceleration: The factors limiting maximum attainable ion energy

Energy Technology Data Exchange (ETDEWEB)

Bulanov, S. S.; Esarey, E.; Schroeder, C. B. [Lawrence Berkeley National Laboratory, Berkeley, California 94720 (United States); Bulanov, S. V. [KPSI, National Institutes for Quantum and Radiological Science and Technology, Kizugawa, Kyoto 619-0215 (Japan); A. M. Prokhorov Institute of General Physics RAS, Moscow 119991 (Russian Federation); Esirkepov, T. Zh.; Kando, M. [KPSI, National Institutes for Quantum and Radiological Science and Technology, Kizugawa, Kyoto 619-0215 (Japan); Pegoraro, F. [Physics Department, University of Pisa and Istituto Nazionale di Ottica, CNR, Pisa 56127 (Italy); Leemans, W. P. [Lawrence Berkeley National Laboratory, Berkeley, California 94720 (United States); Physics Department, University of California, Berkeley, California 94720 (United States)

2016-05-15

Radiation pressure acceleration (RPA) is a highly efficient mechanism of laser-driven ion acceleration, with near complete transfer of the laser energy to the ions in the relativistic regime. However, there is a fundamental limit on the maximum attainable ion energy, which is determined by the group velocity of the laser. The tightly focused laser pulses have group velocities smaller than the vacuum light speed, and, since they offer the high intensity needed for the RPA regime, it is plausible that group velocity effects would manifest themselves in the experiments involving tightly focused pulses and thin foils. However, in this case, finite spot size effects are important, and another limiting factor, the transverse expansion of the target, may dominate over the group velocity effect. As the laser pulse diffracts after passing the focus, the target expands accordingly due to the transverse intensity profile of the laser. Due to this expansion, the areal density of the target decreases, making it transparent for radiation and effectively terminating the acceleration. The off-normal incidence of the laser on the target, due either to the experimental setup, or to the deformation of the target, will also lead to establishing a limit on maximum ion energy.

Risk factors for accelerated polyethylene wear and osteolysis in ABG I total hip arthroplasty

Czech Academy of Sciences Publication Activity Database

Gallo, J.; Havránek, Vítězslav; Zapletová, J.

2013-01-01

Roč. 34, č. 1 (2013), 19-26 ISSN 0341-2695 Grant - others:GA MŠk(CZ) OC 168 Program:OC Institutional research plan: CEZ:AV0Z10100522 Keywords : risk * factors * accelerated * polyethylene * wear * osteolysis * ABG * total * arthroplasty Subject RIV: FI - Traumatology, Orthopedics Impact factor: 2.019, year: 2013

Monte Carlo Method to Study Properties of Acceleration Factor Estimation Based on the Test Results with Varying Load

Directory of Open Access Journals (Sweden)

N. D. Tiannikova

2014-01-01

Full Text Available G.D. Kartashov has developed a technique to determine the rapid testing results scaling functions to the normal mode. Its feature is preliminary tests of products of one sample including tests using the alternating modes. Standard procedure of preliminary tests (researches is as follows: n groups of products with m elements in each start being tested in normal mode and, after a failure of one of products in the group, the remained products are tested in accelerated mode. In addition to tests in alternating mode, tests in constantly normal mode are conducted as well. The acceleration factor of rapid tests for this type of products, identical to any lots is determined using such testing results of products from the same lot. A drawback of this technique is that tests are to be conducted in alternating mode till the failure of all products. That is not always is possible. To avoid this shortcoming, the Renyi criterion is offered. It allows us to determine scaling functions using the right-censored data thus giving the opportunity to stop testing prior to all failures of products.In this work a statistical modeling of the acceleration factor estimation owing to Renyi statistics minimization is implemented by the Monte-Carlo method. Results of modeling show that the acceleration factor estimation obtained through Renyi statistics minimization is conceivable for rather large n . But for small sample volumes some systematic bias of acceleration factor estimation, which decreases with growth n is observed for both distributions (exponential and Veybull's distributions. Therefore the paper also presents calculation results of correction factors for a case of exponential distribution and Veybull's distribution.

Validation of head scatter factor for an Elekta synergy platform linear accelerator

International Nuclear Information System (INIS)

Johannes, N.B.

2013-07-01

A semi-empirical method has been proposed and developed to model and compute head or collimator scatter factors for 6 and 15 MV photon beams from Elekta Synergy platform linear accelerator at the radiation oncology centre of 'Sweden-Ghana Medical Centre Limited', East Legon Hills in Accra. The proposed model was based on two dimensional Gaussian distribution, whose output was compared to measured head scatter factor data for the linear accelerator obtained during commissioning of the teletherapy machine. The two dimensions Gaussian distribution model used physical specifications and configuration of the head unit (collimator system) of the linear accelerator, which were obtained from the user manual provided by the manufacturer of the linear accelerator. The algorithm for the model was implemented using Matlab software in the Microsoft windows environment. The model was done for both square and rectangular fields, and the output compared with corresponding measured data. The comparisons for the square fields were used to establish an error term in the Gaussian distribution function. The error term was determined by plotting the difference between the output factors from MatLab and the corresponding measured data as function of one side of a square field (equivalent square field). The correlation equation of the curve obtained was chosen as the error term, which was incorporated into the Gaussian distribution function. This was repeated for two photon beam energies (6 and 15 MV). The refined Gaussian distributions were then used to determine head scatter factors for square and rectangular fields. For the rectangular fields, Sterling's proposed formula was used to find equivalent square used to obtain the equivalent square fields found in the error terms of the proposed formula was sed to find equivalent square used to obtain the equivalent square fields found in the error terms of the proposed and developed model. The output of the 2D Gaussian distribution without

Heat shock factor-1 intertwines insulin/IGF-1, TGF-β and cGMP signaling to control development and aging

Directory of Open Access Journals (Sweden)

Barna János

2012-11-01

Full Text Available Abstract Background Temperature affects virtually all cellular processes. A quick increase in temperature challenges the cells to undergo a heat shock response to maintain cellular homeostasis. Heat shock factor-1 (HSF-1 functions as a major player in this response as it activates the transcription of genes coding for molecular chaperones (also called heat shock proteins that maintain structural integrity of proteins. However, the mechanisms by which HSF-1 adjusts fundamental cellular processes such as growth, proliferation, differentiation and aging to the ambient temperature remain largely unknown. Results We demonstrate here that in Caenorhabditis elegans HSF-1 represses the expression of daf-7 encoding a TGF-β (transforming growth factor-beta ligand, to induce young larvae to enter the dauer stage, a developmentally arrested, non-feeding, highly stress-resistant, long-lived larval form triggered by crowding and starvation. Under favorable conditions, HSF-1 is inhibited by crowding pheromone-sensitive guanylate cyclase/cGMP (cyclic guanosine monophosphate and systemic nutrient-sensing insulin/IGF-1 (insulin-like growth factor-1 signaling; loss of HSF-1 activity allows DAF-7 to promote reproductive growth. Thus, HSF-1 interconnects the insulin/IGF-1, TGF-β and cGMP neuroendocrine systems to control development and longevity in response to diverse environmental stimuli. Furthermore, HSF-1 upregulates another TGF-β pathway-interacting gene, daf-9/cytochrome P450, thereby fine-tuning the decision between normal growth and dauer formation. Conclusion Together, these results provide mechanistic insight into how temperature, nutrient availability and population density coordinately influence development, lifespan, behavior and stress response through HSF-1.

40 CFR 1033.535 - Adjusting emission levels to account for infrequently regenerating aftertreatment devices.

Science.gov (United States)

2010-07-01

... the downward adjustment factor (DAF) using the following equation: DAF = EFH−EFA (d) Sample... = 0.14 g/ bhp-hr−0.10 g/ bhp-hr = 0.04 g/ bhp-hr. DAF = 0.50 g/ bhp-hr−0.14 g/ bhp-hr = 0.36 g/ bhp-hr...

Royal Jelly-Mediated Prolongevity and Stress Resistance in Caenorhabditis elegans Is Possibly Modulated by the Interplays of DAF-16, SIR-2.1, HCF-1, and 14-3-3 Proteins.

Science.gov (United States)

Wang, Xiaoxia; Cook, Lauren F; Grasso, Lindsay M; Cao, Min; Dong, Yuqing

2015-07-01

Recent studies suggest that royal jelly (RJ) and its related substances may have antiaging properties. However, the molecular mechanisms underlying the beneficial effects remain elusive. We report that the effects of RJ and enzyme-treated RJ (eRJ) on life span and health span in Caenorhabditis elegans (C elegans) are modulated by the sophisticated interplays of DAF-16, SIR-2.1, HCF-1, and 14-3-3 proteins. Dietary supplementation with RJ or eRJ increased C. elegans life span in a dose-dependent manner. The RJ and eRJ consumption increased the tolerance of C elegans to oxidative stress, ultraviolet irradiation, and heat shock stress. Our genetic analyses showed that RJ/eRJ-mediated life-span extension requires insulin/IGF-1 signaling and the activities of DAF-16, SIR-2.1, HCF-1, and FTT-2, a 14-3-3 protein. Earlier studies reported that DAF-16/FOXO, SIR-2.1/SIRT1, FTT-2, and HCF-1 have extensive interplays in worms and mammals. Our present findings suggest that RJ/eRJ-mediated promotion of longevity and stress resistance in C elegans is dependent on these conserved interplays. From an evolutionary point of view, this study not only provides new insights into the molecular mechanisms of RJ's action on health span promotion in C elegans, but also has imperative implications in using RJ/eRJ as nutraceuticals to delay aging and age-related disorders. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

DAF-2 and ERK Couple Nutrient Availability to Meiotic Progression during Caenorhabditis elegans Oogenesis

Science.gov (United States)

Lopez, Andrew L.; Chen, Jessica; Joo, Hyoe-Jin; Drake, Melanie; Shidate, Miri; Kseib, Cedric; Arur, Swathi

2013-01-01

Coupling the production of mature gametes and fertilized zygotes to favorable nutritional conditions improves reproductive success. In invertebrates, the proliferation of female germ line stem cells is regulated by nutritional status. But, in mammals the number of female germ line stem cells is set early in development, with oocytes progressing through meiosis later in life. Mechanisms that couple later steps of oogenesis to environmental conditions remain largely undefined. We show that in the presence of food, the DAF-2 insulin-like receptor signals through the RAS-ERK pathway to drive meiotic prophase I progression and oogenesis; in the absence of food, the resultant inactivation of insulin-like signaling leads to downregulation of RAS-ERK pathway, and oogenesis is stalled. Thus, the insulin-like signaling pathway couples nutrient sensing to meiotic I progression and oocyte production in C. elegans, ensuring that oocytes are only produced under conditions favorable for the survival of the resulting zygotes. PMID:24120884

Evaluation of structure models of Ho2PdSi3 using DAFS, inter alia at a satellite reflection

International Nuclear Information System (INIS)

Nentwich, M; Zschornak, M; Richter, C; Meyer, D C

2014-01-01

The compounds R 2 PdSi 3 , with R = rare earth, exhibit a very interesting magnetic behavior with two phase transitions. Substituting one in four Si atoms by Pd in HoSi 2 results in a modulation of the aristotype. There are several different variants discussed in literature about the nature of the modulation of this rare-earth compound. Two of the latest models were compared: a 2 × 2 × 1 layer and a 2 × 2 × 8 stack. The chosen method is Diffraction Anomalous Fine Structure (DAFS) and was applied both experimentally and by simulation at different absorption edges and reflections, i. a. a satellite reflection, aiming on finding the correct crystal structure

Dynamics and stability of radiation-driven double ablation front structures

International Nuclear Information System (INIS)

Drean, V.; Olazabal-Loume, M.; Tikhonchuk, V. T.; Sanz, J.

2010-01-01

The dynamics of double ablation front (DAF) structures is studied for planar targets with moderate atomic number ablators. These structures are obtained in hydrodynamic simulations for various materials and laser intensities and are qualitatively characterized during the acceleration stage of the target. The importance of the radiative transport for the DAF dynamics is then demonstrated. Simulated hydrodynamic profiles are compared with a theoretical model, showing the consistency of the model and the relevant parameters for the dynamics description. The stability of DAF structures with respect to two-dimensional perturbations is studied using two different approaches: one considers the assumptions of the theoretical model and the other one a more complete physics. The numerical simulations performed with both approaches demonstrate good agreement of dispersion curves.

Accelerator development

International Nuclear Information System (INIS)

Anon.

1975-01-01

Because the use of accelerated heavy ions would provide many opportunities for new and important studies in nuclear physics and nuclear chemistry, as well as other disciplines, both the Chemistry and Physics Divisions are supporting the development of a heavy-ion accelerator. The design of greatest current interest includes a tandem accelerator with a terminal voltage of approximately 25 MV injecting into a linear accelerator with rf superconducting resonators. This combined accelerator facility would be capable of accelerating ions of masses ranging over the entire periodic table to an energy corresponding to approximately 10 MeV/nucleon. This approach, as compared to other concepts, has the advantages of lower construction costs, lower operating power, 100 percent duty factor, and high beam quality (good energy resolution, good timing resolution, small beam size, and small beam divergence). The included sections describe the concept of the proposed heavy-ion accelerator, and the development program aiming at: (1) investigation of the individual questions concerning the superconducting accelerating resonators; (2) construction and testing of prototype accelerator systems; and (3) search for economical solutions to engineering problems. (U.S.)

40 CFR 1042.525 - How do I adjust emission levels to account for infrequently regenerating aftertreatment devices?

Science.gov (United States)

2010-07-01

... the downward adjustment factor (DAF) using the following equation: DAF = EFH−EFA (d) Sample...−0.10 g/kW-hr = 0.04 g/kW-hr. DAF = 0.50 g/kW-hr−0.14 g/kW-hr = 0.36 g/kW-hr. (e) Ramped-modal...

Biological effects of several extreme space flight factors (acceleration, magnetically activated water) on mouse natural or modified radiosensitivity

International Nuclear Information System (INIS)

Datsov, E.R.

1979-01-01

Irradiated and Adeturon-protected mice were used to assess biological effects of several static (magnetically-activated water - MW) and dynamic (acceleration) factors of space flight. The study shows that increased gravitation, 20 G, 5 min, generated by a small radius centrifuge, increases static ability to work, while the number of peripheral blood cells decreases. Continuous exposure of mice to MW induces a decrease in dynamic ability to work, in comparison with the physiological controls, without substantial changes in other indices. Extreme factors in space flight (acceleration MW, radiation, radiation protector), alone or in combination, decrease the animal's growth rate. After administration of 200 mg/kg Adeturone, mouse dynamic ability to work increases, while its capabilities for adaptation and training are lowered, and pronounced leucocytosis is observed. MW, acceleration, or Adeturone pre-treatment of mice increases their survival and dynamic ability to work, following exposure to 600 R, when compared to irradiated animals, but decreases their capabilities for adaptation and training. Acceleration and Adeturone protect peripheral blood from radiation injury, while MW alone intensifies radiation cytopenia. Irradiation does not significantly modify the static ability to work, upon preceding exposure to MW or acceleration. In this case, Adeturone exerts protective effect. ME and Adeturone combined action results in increased survival rate and mean duration of life of irradiated animals, as compared to their single administration. Acceleration reduces MW, Adeturone and MW + Adeturone effect on survival. Peripheral blood parameters do not correlate with survival rates. Combined pre-treatment with two or three of the factors studied increases dynamic ability to work following irradiation, and in many cases the static ability as well. The combination of Adeturone and MW was the only one with negative effect on the static ability to work. (A.B.)

Co-regulation of the DAF-16 target gene, cyp-35B1/dod-13, by HSF-1 in C. elegans dauer larvae and daf-2 insulin pathway mutants.

Directory of Open Access Journals (Sweden)

Wendy B Iser

2011-03-01

Full Text Available Insulin/IGF-I-like signaling (IIS has both cell autonomous and non-autonomous functions. In some cases, targets through which IIS regulates cell-autonomous functions, such as cell growth and metabolism, have been identified. In contrast, targets for many non-autonomous IIS functions, such as C. elegans dauer morphogenesis, remain elusive. Here, we report the use of genomic and genetic approaches to identify potential non-autonomous targets of C. elegans IIS. First, we used transcriptional microarrays to identify target genes regulated non-autonomously by IIS in the intestine or in neurons. C. elegans IIS controls expression of a number of stress response genes, which were differentially regulated by tissue-restricted IIS. In particular, expression of sod-3, a MnSOD enzyme, was not regulated by tissue-restricted IIS on the microarrays, while expression of hsp-16 genes was rescued back to wildtype by tissue restricted IIS. One IIS target regulated non-autonomously by age-1 was cyp-35B1/dod-13, encoding a cytochrome P450. Genetic analysis of the cyp-35B1 promoter showed both DAF-16 and HSF-1 are direct regulators. Based on these findings, we propose that hsf-1 may participate in the pathways mediating non-autonomous activities of age-1 in C. elegans.

Co-regulation of the DAF-16 target gene, cyp-35B1/dod-13, by HSF-1 in C. elegans dauer larvae and daf-2 insulin pathway mutants.

Science.gov (United States)

Iser, Wendy B; Wilson, Mark A; Wood, William H; Becker, Kevin; Wolkow, Catherine A

2011-03-09

Insulin/IGF-I-like signaling (IIS) has both cell autonomous and non-autonomous functions. In some cases, targets through which IIS regulates cell-autonomous functions, such as cell growth and metabolism, have been identified. In contrast, targets for many non-autonomous IIS functions, such as C. elegans dauer morphogenesis, remain elusive. Here, we report the use of genomic and genetic approaches to identify potential non-autonomous targets of C. elegans IIS. First, we used transcriptional microarrays to identify target genes regulated non-autonomously by IIS in the intestine or in neurons. C. elegans IIS controls expression of a number of stress response genes, which were differentially regulated by tissue-restricted IIS. In particular, expression of sod-3, a MnSOD enzyme, was not regulated by tissue-restricted IIS on the microarrays, while expression of hsp-16 genes was rescued back to wildtype by tissue restricted IIS. One IIS target regulated non-autonomously by age-1 was cyp-35B1/dod-13, encoding a cytochrome P450. Genetic analysis of the cyp-35B1 promoter showed both DAF-16 and HSF-1 are direct regulators. Based on these findings, we propose that hsf-1 may participate in the pathways mediating non-autonomous activities of age-1 in C. elegans.

Carnitine protects the nematode Caenorhabditis elegans from glucose-induced reduction of survival depending on the nuclear hormone receptor DAF-12

International Nuclear Information System (INIS)

Deusing, Dorothé Jenni; Beyrer, Melanie; Fitzenberger, Elena; Wenzel, Uwe

2015-01-01

Besides its function in transport of fatty acids into mitochondria in order to provide substrates for β-oxidation, carnitine has been shown to affect also glucose metabolism and to inhibit several mechanisms associated with diabetic complications. In the present study we used the mev-1 mutant of the nematode Caenorhabditis elegans fed on a high glucose concentration in liquid media as a diabetes model and tested the effects of carnitine supplementation on their survival under heat-stress. Carnitine at 100 μM completely prevented the survival reduction that was caused by the application of 10 mM glucose. RNA-interference for sir-2.1, a candidate genes mediating the effects of carnitine revealed no contribution of the sirtuin for the rescue of survival. Under daf-12 RNAi rescue of survival by carnitine was abolished. RNA-interference for γ-butyrobetaine hydroxylase 2, encoding the key enzyme for carnitine biosynthesis did neither increase glucose toxicity nor prevent the rescue of survival by carnitine, suggesting that the effects of carnitine supplementation on carnitine levels were significant. Finally, it was demonstrated that neither the amount of lysosomes nor the proteasomal activity were increased by carnitine, excluding that protein degradation pathways, such as autophagy or proteasomal degradation, are involved in the protective carnitine effects. In conclusion, carnitine supplementation prevents the reduction of survival caused by glucose in C. elegans in dependence on a nuclear hormone receptor which displays high homologies to the vertebrate peroxisomal proliferator activated receptors. - Highlights: • Carnitine protects from glucose-induced reduction of stress-resistance. • Carnitine acts via the PPAR homolog DAF-12 on glucose toxicity. • Carnitine protects from glucose toxicity independent of protein degradation

Carnitine protects the nematode Caenorhabditis elegans from glucose-induced reduction of survival depending on the nuclear hormone receptor DAF-12

Energy Technology Data Exchange (ETDEWEB)

Deusing, Dorothé Jenni, E-mail: Dorothe.J.Deusing@ernaehrung.uni-giessen.de; Beyrer, Melanie, E-mail: m.beyrer@web.de; Fitzenberger, Elena, E-mail: Elena.Fitzenberger@ernaehrung.uni-giessen.de; Wenzel, Uwe, E-mail: uwe.wenzel@ernaehrung.uni-giessen.de

2015-05-08

Besides its function in transport of fatty acids into mitochondria in order to provide substrates for β-oxidation, carnitine has been shown to affect also glucose metabolism and to inhibit several mechanisms associated with diabetic complications. In the present study we used the mev-1 mutant of the nematode Caenorhabditis elegans fed on a high glucose concentration in liquid media as a diabetes model and tested the effects of carnitine supplementation on their survival under heat-stress. Carnitine at 100 μM completely prevented the survival reduction that was caused by the application of 10 mM glucose. RNA-interference for sir-2.1, a candidate genes mediating the effects of carnitine revealed no contribution of the sirtuin for the rescue of survival. Under daf-12 RNAi rescue of survival by carnitine was abolished. RNA-interference for γ-butyrobetaine hydroxylase 2, encoding the key enzyme for carnitine biosynthesis did neither increase glucose toxicity nor prevent the rescue of survival by carnitine, suggesting that the effects of carnitine supplementation on carnitine levels were significant. Finally, it was demonstrated that neither the amount of lysosomes nor the proteasomal activity were increased by carnitine, excluding that protein degradation pathways, such as autophagy or proteasomal degradation, are involved in the protective carnitine effects. In conclusion, carnitine supplementation prevents the reduction of survival caused by glucose in C. elegans in dependence on a nuclear hormone receptor which displays high homologies to the vertebrate peroxisomal proliferator activated receptors. - Highlights: • Carnitine protects from glucose-induced reduction of stress-resistance. • Carnitine acts via the PPAR homolog DAF-12 on glucose toxicity. • Carnitine protects from glucose toxicity independent of protein degradation.

40 CFR 1039.525 - How do I adjust emission levels to account for infrequently regenerating aftertreatment devices?

Science.gov (United States)

2010-07-01

... measured emission rate. Determine the downward adjustment factor (DAF) using the following equation: DAF... g/kW-hr. UAF = 0.14 g/kW-hr − 0.10 g/kW-hr = 0.04 g/kW-hr. DAF = 0.50 g/kW-hr − 0.14 g/kW-hr = 0.36...

Platelet factor XIII increases the fibrinolytic resistance of platelet-rich clots by accelerating the crosslinking of alpha 2-antiplasmin to fibrin

Science.gov (United States)

Reed, G. L.; Matsueda, G. R.; Haber, E.

1992-01-01

Platelet clots resist fibrinolysis by plasminogen activators. We hypothesized that platelet factor XIII may enhance the fibrinolytic resistance of platelet-rich clots by catalyzing the crosslinking of alpha 2-antiplasmin (alpha 2AP) to fibrin. Analysis of plasma clot structure by polyacrylamide gel electrophoresis and immunoblotting revealed accelerated alpha 2AP-fibrin crosslinking in platelet-rich compared with platelet-depleted plasma clots. A similar study of clots formed with purified fibrinogen (depleted of factor XIII activity), isolated platelets, and specific factor XIII inhibitors indicated that this accelerated crosslinking was due to the catalytic activity of platelet factor XIII. Moreover, when washed platelets were aggregated by thrombin, there was evidence of platelet factor XIII-mediated crosslinking between platelet alpha 2AP and platelet fibrin(ogen). Specific inhibition (by a monoclonal antibody) of the alpha 2AP associated with washed platelet aggregates accelerated the fibrinolysis of the platelet aggregate. Thus in platelet-rich plasma clots, and in thrombin-induced platelet aggregates, platelet factor XIII actively formed alpha 2AP-fibrin crosslinks, which appeared to enhance the resistance of platelet-rich clots to fibrinolysis.

Co-chaperone p23 regulates C. elegans Lifespan in Response to Temperature.

Directory of Open Access Journals (Sweden)

Makoto Horikawa

2015-04-01

Full Text Available Temperature potently modulates various physiologic processes including organismal motility, growth rate, reproduction, and ageing. In ectotherms, longevity varies inversely with temperature, with animals living shorter at higher temperatures. Thermal effects on lifespan and other processes are ascribed to passive changes in metabolic rate, but recent evidence also suggests a regulated process. Here, we demonstrate that in response to temperature, daf-41/ZC395.10, the C. elegans homolog of p23 co-chaperone/prostaglandin E synthase-3, governs entry into the long-lived dauer diapause and regulates adult lifespan. daf-41 deletion triggers constitutive entry into the dauer diapause at elevated temperature dependent on neurosensory machinery (daf-10/IFT122, insulin/IGF-1 signaling (daf-16/FOXO, and steroidal signaling (daf-12/FXR. Surprisingly, daf-41 mutation alters the longevity response to temperature, living longer than wild-type at 25°C but shorter than wild-type at 15°C. Longevity phenotypes at 25°C work through daf-16/FOXO and heat shock factor hsf-1, while short lived phenotypes converge on daf-16/FOXO and depend on the daf-12/FXR steroid receptor. Correlatively daf-41 affected expression of DAF-16 and HSF-1 target genes at high temperature, and nuclear extracts from daf-41 animals showed increased occupancy of the heat shock response element. Our studies suggest that daf-41/p23 modulates key transcriptional changes in longevity pathways in response to temperature.

Dynamics and acceleration in linear structures

International Nuclear Information System (INIS)

Le Duff, J.

1985-06-01

Basic methods of linear acceleration are reviewed. Both cases of non relativistic and ultra relativistic particles are considered. Induction linac, radiofrequency quadrupole are mentioned. Fundamental parameters of accelerating structures are recalled; they are transit time factor, shunt impedance, quality factor and stored energy, phase velocity and group velocity, filling time, space harmonics in loaded waveguides. Energy gain in linear accelerating structures is considered through standing wave structures and travelling wave structures. Then particle dynamics in linear accelerators is studied: longitudinal motion, transverse motion and dynamics in RFQ

Final Design for an International Intercomparison Exercise for Nuclear Accident Dosimetry at the DAF Using Godiva-IV: IER-148 CED-2 Report

Energy Technology Data Exchange (ETDEWEB)

Heinrichs, Dave [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Beller, Tim [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Burch, Jennifer [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Cummings, Rick [National Security Technologies, LLC. (NSTec), Mercury, NV (United States) Nevada National Security Site; Duluc, Matthieu [Inst. de Radioprotection et de Sûrete Nucleaire (ISRN), Fontenay-aux-Roses (France); Gadd, Milan [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Goda, Joetta [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Hickman, David [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); McAvoy, Doug [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Rathbone, Bruce [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Sullivan, Randy [Savannah River Site (SRS), Aiken, SC (United States); Trompier, Francois [Inst. de Radioprotection et de Sûrete Nucleaire (ISRN), Fontenay-aux-Roses (France); Veinot, Ken [Y-12 National Security Complex, Oak Ridge, TN (United States); Ward, Dann [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Will, Rashelle [National Security Technologies, LLC. (NSTec), Mercury, NV (United States) Nevada National Security Site; Wilson, Chris [Atomic Weapons Establishment (AWE), Berkshire (United Kingdom); Zieziulewicz, Thomas [Knolls Atomic Power Lab. (KAPL), Niskayuna, NY (United States)

2014-09-30

This document is the Final Design (CED-2) Report for IER-148, “International Inter-comparison Exercise for Nuclear Accident Dosimetry at the DAF Using Godiva-IV.” The report describes the structure of the exercise consisting of three irradiations; identifies the participating laboratories and their points of contact; provides the details of all dosimetry elements and their placement in proximity to Godiva-IV on support stands or phantoms ; and lists the counting and spectroscopy equipment each laboratory will utilize in the Mercury NAD Lab. The exercise is tentatively scheduled for one week in August 2015.

Comparison of the Soil Dynamic Amplification Factor and Soil Amplification by Using Microtremor and MASW Methods Respectively

Science.gov (United States)

Tuncel, Aykut; Cevdet Özdag, Özkan; Pamuk, Eren; Akgün, Mustafa

2017-12-01

Single Station Microtremor method, which is widely used nowadays, is an effective and easy applicable method. In this study, dynamic amplification factor distributions of the study area were obtained using scenario earthquake parameters with single station microtremor data gathered at 112 points. In addition, a surface wave active method, which is known as MASW (Multichannel Analysis of Surface Waves), was applied at 43 profiles to calculate the soil amplification values. Dynamic amplification factor (DAF), soil amplification, the predominant soil period (PSP), geology and topography data of the study area were analysed together. Dynamic amplification factor and soil amplification values were obtained 2 or higher at about sea level parts of the study area which are generally composed of alluvial units. Additionally, in high altitude regions that are composed of volcanic rocks, relatively lower dynamic amplification factor and soil amplification values were obtained. The minimum amplification value in the study area was 1.15, while the maximum amplification value was 3.05 according to the dynamic amplification results and the soil amplification values were between 1.16 and 3.85 in harmony. It is seen that the obtained DAF values and the soil amplification values calculated from the seismic velocities are very similar to each other numerically and regionally. Because of this, it is concluded that the values of the soil amplification obtained by the MASW method and the calculated DAF values in this study are in harmony with each other. Although the depths of research in these two calculation methods are different from each other, the similarity of the results allows us to arrive at the result of how effective the ground layer is on the amplification. It has a great importance to calculate the amplification values and other dynamic parameters by in situ measurements for a planned plot because geological units can vary even at very short distances in heterogeneously

The Factor Inhibiting HIF Asparaginyl Hydroxylase Regulates Oxidative Metabolism and Accelerates Metabolic Adaptation to Hypoxia.

Science.gov (United States)

Sim, Jingwei; Cowburn, Andrew S; Palazon, Asis; Madhu, Basetti; Tyrakis, Petros A; Macías, David; Bargiela, David M; Pietsch, Sandra; Gralla, Michael; Evans, Colin E; Kittipassorn, Thaksaon; Chey, Yu C J; Branco, Cristina M; Rundqvist, Helene; Peet, Daniel J; Johnson, Randall S

2018-04-03

Animals require an immediate response to oxygen availability to allow rapid shifts between oxidative and glycolytic metabolism. These metabolic shifts are highly regulated by the HIF transcription factor. The factor inhibiting HIF (FIH) is an asparaginyl hydroxylase that controls HIF transcriptional activity in an oxygen-dependent manner. We show here that FIH loss increases oxidative metabolism, while also increasing glycolytic capacity, and that this gives rise to an increase in oxygen consumption. We further show that the loss of FIH acts to accelerate the cellular metabolic response to hypoxia. Skeletal muscle expresses 50-fold higher levels of FIH than other tissues: we analyzed skeletal muscle FIH mutants and found a decreased metabolic efficiency, correlated with an increased oxidative rate and an increased rate of hypoxic response. We find that FIH, through its regulation of oxidation, acts in concert with the PHD/vHL pathway to accelerate HIF-mediated metabolic responses to hypoxia. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Design, performance and economics of the DAF Indal 50 kW and 375 kW vertical axis wind turbine

Science.gov (United States)

Schienbein, L. A.; Malcolm, D. J.

1982-03-01

A review of the development and performance of the DAF Indal 50 kW vertical axis Darrieus wind turbines shows that a high level of technical development and reliability has been achieved. Features of the drive train, braking and control systems are discussed and performance details are presented. A description is given of a wind-diesel hybrid presently being tested. Details are also presented of a 375 kW VAWT planned for production in late 1982. A discussion of the economics of both the 50 kW and 375 kW VAWTs is included, showing the effects of charge rate, installed cost, operating cost, performance and efficiency. The energy outputs are translated into diesel fuel cost savings for remote communities.

Theory of factors limiting high gradient operation of warm accelerating structures

Energy Technology Data Exchange (ETDEWEB)

Nusinovich, Gregory S. [University of Maryland; Antonsen, Thomas M. [University of Maryland; Kishek, Rami [University of Maryland

2014-07-25

This final report summarizes the research performed during the time period from 8/1/2010 to 7/31/2013. It consists of two parts describing our studies in two directions: (a) analysis of factors limiting operation of dielectric-loaded accelerating (DLA) structures where the main problem is the occurrence of multipactor on dielectric surfaces, and (b) studies of effects associated with either RF magnetic or RF electric fields which may cause the RF breakdown in high-gradient metallic accelerating structures. In the studies of DLA structures, at least, two accomplishments should be mentioned: the development of a 3D non-stationary, self-consistent code describing the multipactor phenomena and yielding very good agreement with some experimental data obtained in joint ANL/NRL experiments. In the metallic structures, such phenomena as the heating and melting of micro-particles (metallic dust) by RF electric and magnetic fields in single-shot and rep-rate regimes is analyzed. Also, such processes in micro-protrusions on the structure surfaces as heating and melting due to the field emitted current and the Nottingham effect are thoroughly investigated with the account for space charge of emitted current on the field emission from the tip.

Comparative study between output factors obtained in a linear accelerator used for radiosurgery treatments

International Nuclear Information System (INIS)

Velázquez Trejo, J.J.; Olive, K.I.; Gutiérrez Castillo, J.G.; Hardy Pérez, A.E.

2017-01-01

Purpose: To compare the output factors obtained in a linear accelerator with conical collimators using five models of detectors, through tree different methods: the ratio of detector readings, the “daisy chain” technique (for diodes) and applying the k fclin, fmsr Qclin, Qmsr factors based in the formalism proposed by the IAEA (this one was applied only to tree detectors). Methods: A linear accelerator Varian-iX was employed with BrainLab conical collimators (30 mm to 7.5 mm), the detectors used were: PTW-PinPoint 31016 (×2), PTW-tipo E 60017 (×2), PTW-microLion 31018 (×2), EDGE (Sun-Nuclear), y PTW-Semiflex 31010. For the first three models were analyzed two detectors with different series. The measurements were carried out in water at depth of 1.5 cm and source to surface distance of 98.5 cm. Results: With the readings ratio method, all detectors showed differences from 3.5% to more than 15% in the smallest field sizes, for the diodes the “daisy chain” method did not provide significant corrections. Applying the k fclin, fmsr Qclin, Qmsr Small the detectors PTW60017, PTW31018 and EDGE showed differences of less than 3%. Conclusions: In small fields the readings ratio method could introduce significant errors in the output factor determination. Applying the k fclin, fmsr Qclin, Qmsr proved to be a viable option. [es

An Examination of Resonance, Acceleration, and Particle Dynamics in the Micro-Accelerator Platform

International Nuclear Information System (INIS)

McNeur, Josh; Rosenzweig, J. B.; Travish, G.; Zhou, J.; Yoder, R.

2010-01-01

An effort to build a micron-scale dielectric-based slab-symmetric accelerator is underway at UCLA. The structure achieves acceleration via a resonant accelerating mode that is excited in an approximately 800 nm wide vacuum gap by a side coupled 800 nm laser. Detailed simulation results on structure fields and particle dynamics, using HFSS and VORPAL, are presented. We examine the quality factors of the accelerating modes for various structures and the excitations of non-accelerating destructive modes. Additionally, the results of an analytic and computational study of focusing, longitudinal dynamics and acceleration are described. Methods for achieving simultaneous transverse and longitudinal focusing are discussed, including modification of structure dimensions and slow variation of the coupling periodicity.

Factors associated with accelerated subclinical atherosclerosis in patients with spondyloarthritis without overt cardiovascular disease.

Science.gov (United States)

Giollo, Alessandro; Dalbeni, Andrea; Cioffi, Giovanni; Ognibeni, Federica; Gatti, Davide; Idolazzi, Luca; Orsolini, Giovanni; Minuz, Pietro; Rossini, Maurizio; Fava, Cristiano; Viapiana, Ombretta

2017-11-01

Data on the progression of atherosclerosis in spondyloarthritis (SpA) are scarce, despite a high burden of cardiovascular diseases (CVD). The aim of this study was to identify the predictors of an accelerated subclinical atherosclerosis in patients with SpA. Study participants were 66 patients free of CVD classified according to ASAS criteria. The patients were evaluated at baseline and after 13.5 ± 3.6 months. Ultrasound measurements of carotid intima-media thickness (cIMT) and distensibility coefficient (cDC) were used to assess the extent of subclinical atherosclerosis. cIMT progression rate was calculated dividing the cIMT change by the time between the scans. Accelerated atherosclerosis was defined as the top cIMT progression rate quartile. At baseline, the mean Framingham Risk Score was 14 ± 11%. At follow-up, cIMT increased in 39 patients (59%; mean difference 0.01 ± 0.10; p = 0.334). Mean cIMT progression rate was 0.01 mm/year (95% CI - 0.02 to 0.03). cDC was unchanged at follow-up. Patients with accelerated atherosclerosis (n = 16) had significantly higher serum creatinine and lower glomerular filtration rate (eGFR) at baseline. In multiple logistic regression, only eGFR and the presence of syndesmophytes were associated with an accelerated atherosclerosis, independent of traditional cardiovascular risk factors. In patients with SpA without overt CV disease, a decrease in renal function and radiographic damage are conditions associated with the development of subclinical accelerated atherosclerosis. Longitudinal assessment of cIMT could be useful to better evaluate the individual CV risk of these patients improving their prognostic stratification.

FFAGS for muon acceleration

International Nuclear Information System (INIS)

Berg, J. Scott; Kahn, Stephen; Palmer, Robert; Trbojevic, Dejan; Johnstone, Carol; Keil, Eberhard; Aiba, Masamitsu; Machida, Shinji; Mori, Yoshiharu; Ogitsu, Toru; Ohmori, Chihiro; Sessler, Andrew; Koscielniak, Shane

2003-01-01

Due to their finite lifetime, muons must be accelerated very rapidly. It is challenging to make the magnets ramp fast enough to accelerate in a synchrotron, and accelerating in a linac is very expensive. One can use a recirculating accelerator (like CEBAF), but one needs a different arc for each turn, and this limits the number of turns one can use to accelerate, and therefore requires significant amounts of RF to achieve the desired energy gain. An alternative method for muon acceleration is using a fixed field alternating gradient (FFAG) accelerator. Such an accelerator has a very large energy acceptance (a factor of two or three), allowing one to use the same arc with a magnetic field that is constant over time. Thus, one can in principle make as many turns as one can tolerate due to muon decay, therefore reducing the RF cost without increasing the arc cost. This paper reviews the current status of research into the design of FFAGs for muon acceleration. Several current designs are described and compared. General design considerations are also discussed

An acceleration of the characteristics by a space-angle two-level method using surface discontinuity factors

Energy Technology Data Exchange (ETDEWEB)

Grassi, G. [Commissariat a l' Energie Atomique, CEA de Saclay, DM2S/SERMA/LENR, 91191, Gif-sur-Yvette (France)

2006-07-01

We present a non-linear space-angle two-level acceleration scheme for the method of the characteristics (MOC). To the fine level on which the MOC transport calculation is performed, we associate a more coarsely discretized phase space in which a low-order problem is solved as an acceleration step. Cross sections on the coarse level are obtained by a flux-volume homogenisation technique, which entails the non-linearity of the acceleration. Discontinuity factors per surface are introduced as additional degrees of freedom on the coarse level in order to ensure the equivalence of the heterogeneous and the homogenised problem. After each fine transport iteration, a low-order transport problem is iteratively solved on the homogenised grid. The solution of this problem is then used to correct the angular moments of the flux resulting from the previous free transport sweep. Numerical tests for a given benchmark have been performed. Results are discussed. (authors)

An acceleration of the characteristics by a space-angle two-level method using surface discontinuity factors

International Nuclear Information System (INIS)

Grassi, G.

2006-01-01

We present a non-linear space-angle two-level acceleration scheme for the method of the characteristics (MOC). To the fine level on which the MOC transport calculation is performed, we associate a more coarsely discretized phase space in which a low-order problem is solved as an acceleration step. Cross sections on the coarse level are obtained by a flux-volume homogenisation technique, which entails the non-linearity of the acceleration. Discontinuity factors per surface are introduced as additional degrees of freedom on the coarse level in order to ensure the equivalence of the heterogeneous and the homogenised problem. After each fine transport iteration, a low-order transport problem is iteratively solved on the homogenised grid. The solution of this problem is then used to correct the angular moments of the flux resulting from the previous free transport sweep. Numerical tests for a given benchmark have been performed. Results are discussed. (authors)

The Somatic Reproductive Tissues of C. elegans Promote Longevity through Steroid Hormone Signaling

Science.gov (United States)

Yamawaki, Tracy M.; Berman, Jennifer R.; Suchanek-Kavipurapu, Monika; McCormick, Mark; Gaglia, Marta Maria; Lee, Seung-Jae; Kenyon, Cynthia

2010-01-01

In Caenorhabditis elegans and Drosophila melanogaster, removing the germline precursor cells increases lifespan. In worms, and possibly also in flies, this lifespan extension requires the presence of somatic reproductive tissues. How the somatic gonad signals other tissues to increase lifespan is not known. The lifespan increase triggered by loss of the germ cells is known to require sterol hormone signaling, as reducing the activity of the nuclear hormone receptor DAF-12, or genes required for synthesis of the DAF-12 ligand dafachronic acid, prevents germline loss from extending lifespan. In addition to sterol signaling, the FOXO transcription factor DAF-16 is required to extend lifespan in animals that lack germ cells. DAF-12/NHR is known to assist with the nuclear accumulation of DAF-16/FOXO in these animals, yet we find that loss of DAF-12/NHR has little or no effect on the expression of at least some DAF-16/FOXO target genes. In this study, we show that the DAF-12-sterol signaling pathway has a second function to activate a distinct set of genes and extend lifespan in response to the somatic reproductive tissues. When germline-deficient animals lacking somatic reproductive tissues are given dafachronic acid, their expression of DAF-12/NHR-dependent target genes is restored and their lifespan is increased. Together, our findings indicate that in C. elegans lacking germ cells, the somatic reproductive tissues promote longevity via steroid hormone signaling to DAF-12. PMID:20824162

The somatic reproductive tissues of C. elegans promote longevity through steroid hormone signaling.

Directory of Open Access Journals (Sweden)

Tracy M Yamawaki

2010-08-01

Full Text Available In Caenorhabditis elegans and Drosophila melanogaster, removing the germline precursor cells increases lifespan. In worms, and possibly also in flies, this lifespan extension requires the presence of somatic reproductive tissues. How the somatic gonad signals other tissues to increase lifespan is not known. The lifespan increase triggered by loss of the germ cells is known to require sterol hormone signaling, as reducing the activity of the nuclear hormone receptor DAF-12, or genes required for synthesis of the DAF-12 ligand dafachronic acid, prevents germline loss from extending lifespan. In addition to sterol signaling, the FOXO transcription factor DAF-16 is required to extend lifespan in animals that lack germ cells. DAF-12/NHR is known to assist with the nuclear accumulation of DAF-16/FOXO in these animals, yet we find that loss of DAF-12/NHR has little or no effect on the expression of at least some DAF-16/FOXO target genes. In this study, we show that the DAF-12-sterol signaling pathway has a second function to activate a distinct set of genes and extend lifespan in response to the somatic reproductive tissues. When germline-deficient animals lacking somatic reproductive tissues are given dafachronic acid, their expression of DAF-12/NHR-dependent target genes is restored and their lifespan is increased. Together, our findings indicate that in C. elegans lacking germ cells, the somatic reproductive tissues promote longevity via steroid hormone signaling to DAF-12.

Nonlinear acceleration of transport criticality problems

International Nuclear Information System (INIS)

Park, H.; Knoll, D.A.; Newman, C.K.

2011-01-01

We present a nonlinear acceleration algorithm for the transport criticality problem. The algorithm combines the well-known nonlinear diffusion acceleration (NDA) with a recently developed, Newton-based, nonlinear criticality acceleration (NCA) algorithm. The algorithm first employs the NDA to reduce the system to scalar flux, then the NCA is applied to the resulting drift-diffusion system. We apply a nonlinear elimination technique to eliminate the eigenvalue from the Jacobian matrix. Numerical results show that the algorithm reduces the CPU time a factor of 400 in a very diffusive system, and a factor of 5 in a non-diffusive system. (author)

Moonshot Acceleration Factor: Medical Imaging.

Science.gov (United States)

Sevick-Muraca, Eva M; Frank, Richard A; Giger, Maryellen L; Mulshine, James L

2017-11-01

Medical imaging is essential to screening, early diagnosis, and monitoring responses to cancer treatments and, when used with other diagnostics, provides guidance for clinicians in choosing the most effective patient management plan that maximizes survivorship and quality of life. At a gathering of agency officials, patient advocacy organizations, industry/professional stakeholder groups, and clinical/basic science academicians, recommendations were made on why and how one should build a "cancer knowledge network" that includes imaging. Steps to accelerate the translation and clinical adoption of cancer discoveries to meet the goals of the Cancer Moonshot include harnessing computational power and architectures, developing data sharing policies, and standardizing medical imaging and in vitro diagnostics. Cancer Res; 77(21); 5717-20. ©2017 AACR . ©2017 American Association for Cancer Research.

Intestinal Insulin Signaling Encodes Two Different Molecular Mechanisms for the Shortened Longevity Induced by Graphene Oxide in Caenorhabditis elegans

Science.gov (United States)

Zhao, Yunli; Yang, Ruilong; Rui, Qi; Wang, Dayong

2016-04-01

Graphene oxide (GO) has been shown to cause multiple toxicities in various organisms. However, the underlying molecular mechanisms for GO-induced shortened longevity are still unclear. We employed Caenorhabditis elegans to investigate the possible involvement of insulin signaling pathway in the control of GO toxicity and its underlying molecular mechanisms. Mutation of daf-2, age-1, akt-1, or akt-2 gene induced a resistant property of nematodes to GO toxicity, while mutation of daf-16 gene led to a susceptible property of nematodes to GO toxicity, suggesting that GO may dysregulate the functions of DAF-2/IGF-1 receptor, AGE-1, AKT-1 and AKT-2-mediated kinase cascade, and DAF-16/FOXO transcription factor. Genetic interaction analysis suggested the involvement of signaling cascade of DAF-2-AGE-1-AKT-1/2-DAF-16 in the control of GO toxicity on longevity. Moreover, intestinal RNA interference (RNAi) analysis demonstrated that GO reduced longevity by affecting the functions of signaling cascade of DAF-2-AGE-1-AKT-1/2-DAF-16 in the intestine. DAF-16 could also regulate GO toxicity on longevity by functioning upstream of SOD-3, which encodes an antioxidation system that prevents the accumulation of oxidative stress. Therefore, intestinal insulin signaling may encode two different molecular mechanisms responsible for the GO toxicity in inducing the shortened longevity. Our results highlight the key role of insulin signaling pathway in the control of GO toxicity in organisms.

Exogenous endothelial cells as accelerators of hematopoietic reconstitution

Directory of Open Access Journals (Sweden)

Mizer J

2012-11-01

Full Text Available Abstract Despite the successes of recombinant hematopoietic-stimulatory factors at accelerating bone marrow reconstitution and shortening the neutropenic period post-transplantation, significant challenges remain such as cost, inability to reconstitute thrombocytic lineages, and lack of efficacy in conditions such as aplastic anemia. A possible means of accelerating hematopoietic reconstitution would be administration of cells capable of secreting hematopoietic growth factors. Advantages of this approach would include: a ability to regulate secretion of cytokines based on biological need; b long term, localized production of growth factors, alleviating need for systemic administration of factors that possess unintended adverse effects; and c potential to actively repair the hematopoietic stem cell niche. Here we overview the field of hematopoietic growth factors, discuss previous experiences with mesenchymal stem cells (MSC in accelerating hematopoiesis, and conclude by putting forth the rationale of utilizing exogenous endothelial cells as a novel cellular therapy for acceleration of hematopoietic recovery.

Accelerators course

CERN Multimedia

CERN. Geneva HR-RFA; Métral, E

2006-01-01

1a) Introduction and motivation 1b) History and accelerator types 2) Transverse beam dynamics 3a) Longitudinal beam dynamics 3b) Figure of merit of a synchrotron/collider 3c) Beam control 4) Main limiting factors 5) Technical challenges

Auroral electron acceleration

International Nuclear Information System (INIS)

Bryant, D.A.

1989-10-01

Two theories of auroral electron acceleration are discussed. Part 1 examines the currently widely held view that the acceleration is an ordered process in a quasi-static electric field. It is suggested that, although there are many factors seeming to support this theory, the major qualifications and uncertainties that have been identified combine to cast serious doubt over its validity. Part 2 is devoted to a relatively new interpretation in terms of stochastic acceleration in turbulent electric fields. This second theory, which appears to account readily for most known features of the electron distribution function, is considered to provide a more promising approach to this central question in magnetospheric plasma physics. (author)

Dataset of the human homologues and orthologues of lipid-metabolic genes identified as DAF-16 targets their roles in lipid and energy metabolism.

Science.gov (United States)

Fan, Lavender Yuen-Nam; Saavedra-García, Paula; Lam, Eric Wing-Fai

2017-04-01

The data presented in this article are related to the review article entitled 'Unravelling the role of fatty acid metabolism in cancer through the FOXO3-FOXM1 axis' (Saavedra-Garcia et al., 2017) [24]. Here, we have matched the DAF-16/FOXO3 downstream genes with their respective human orthologues and reviewed the roles of these targeted genes in FA metabolism. The list of genes listed in this article are precisely selected from literature reviews based on their functions in mammalian FA metabolism. The nematode Caenorhabditis elegans gene orthologues of the genes are obtained from WormBase, the online biological database of C. elegans. This dataset has not been uploaded to a public repository yet.

Recent technological developments in accelerating structures

International Nuclear Information System (INIS)

Yamazaki, Y.

1992-01-01

A variety of high-β accelerating structures for both proton and electron accelerators are reviewed from modern points of view. Both standing-and traveling-wave structures are discussed. Beam stability is one of the most important factors which must be taken into account regarding modern accelerators in which the beam intensity is an issue. (Author) 3 figs., 3 tabs., 60 refs

Function of the PHA-4/FOXA transcription factor during C. elegans post-embryonic development

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Chen Di

2008-02-01

Full Text Available Abstract Background pha-4 encodes a forkhead box (FOX A transcription factor serving as the C. elegans pharynx organ identity factor during embryogenesis. Using Serial Analysis of Gene Expression (SAGE, comparison of gene expression profiles between growing stages animals and long-lived, developmentally diapaused dauer larvae revealed that pha-4 transcription is increased in the dauer stage. Results Knocking down pha-4 expression by RNAi during post-embryonic development showed that PHA-4 is essential for dauer recovery, gonad and vulva development. daf-16, which encodes a FOXO transcription factor regulated by insulin/IGF-1 signaling, shows overlapping expression patterns and a loss-of-function post-embryonic phenotype similar to that of pha-4 during dauer recovery. pha-4 RNAi and daf-16 mutations have additive effects on dauer recovery, suggesting these two regulators may function in parallel pathways. Gene expression studies using RT-PCR and GFP reporters showed that pha-4 transcription is elevated under starvation, and a conserved forkhead transcription factor binding site in the second intron of pha-4 is important for the neuronal expression. The vulval transcription of lag-2, which encodes a ligand for the LIN-12/Notch lateral signaling pathway, is inhibited by pha-4 RNAi, indicating that LAG-2 functions downstream of PHA-4 in vulva development. Conclusion Analysis of PHA-4 during post-embryonic development revealed previously unsuspected functions for this important transcriptional regulator in dauer recovery, and may help explain the network of transcriptional control integrating organogenesis with the decision between growth and developmental arrest at the dauer entry and exit stages.

An investigation of accelerator head scatter and output factor in air

International Nuclear Information System (INIS)

Ding, George X.

2004-01-01

Our purpose in this study was to investigate whether the Monte Carlo simulation can accurately predict output factors in air. Secondary goals were to study the head scatter components and investigate the collimator exchange effect. The Monte Carlo code, BEAMnrc, was used in the study. Photon beams of 6 and 18 MV were from a Varian Clinac 2100EX accelerator and the measurements were performed using an ionization chamber in a mini-phantom. The Monte Carlo calculated in air output factors was within 1% of measured values. The simulation provided information of the origin and the magnitude of the collimator exchange effect. It was shown that the collimator backscatter to the beam monitor chamber played a significant role in the beam output factors. However the magnitude of the scattered dose contributions from the collimator at the isocenter is negligible. The maximum scattered dose contribution from the collimators was about 0.15% and 0.4% of the total dose at the isocenter for a 6 and 18 MV beam, respectively. The scattered dose contributions from the flattening filter at the isocenter were about 0.9-3% and 0.2-6% of the total dose for field sizes of 4x4 cm 2 -40x40 cm 2 for the 6 and 18 MV beam, respectively. The study suggests that measurements of head scatter factors be done at large depth well beyond the depth of electron contamination. The insight information may have some implications for developing generalized empirical models to calculate the head scatter

Accelerator applications in energy and security

CERN Document Server

Chou, Weiren

2015-01-01

As accelerator science and technology progressed over the past several decades, the accelerators themselves have undergone major improvements in multiple performance factors: beam energy, beam power, and beam brightness. As a consequence, accelerators have found applications in a wide range of fields in our life and in our society. The current volume is dedicated to applications in energy and security, two of the most important and urgent topics in today's world. This volume makes an effort to provide a review as complete and up to date as possible of this broad and challenging subject. It contains overviews on each of the two topics and a series of articles for in-depth discussions including heavy ion accelerator driven inertial fusion, linear accelerator-based ADS systems, circular accelerator-based ADS systems, accelerator-reactor interface, accelerators for fusion material testing, cargo inspection, proton radiography, compact neutron generators and detectors. It also has a review article on accelerator ...

Theory of factors limiting high gradient operation of warm accelerating structures

Energy Technology Data Exchange (ETDEWEB)

Nusinovich, Gregory S. [Univ. of Maryland, College Park, MD (United States)

2014-07-22

This report consists of two parts. In the first part we describe a study of the heating of microprotrusions on surfaces of accelerating structures. This ;process is believed to lead to breakdown in these structures. Our study revealed that for current accelerator parameters melting should not occur due to space charge limitations of the current emitted by a protrusion. The second part describes a novel concept to develop THz range sources based on harmonic cyclotron masers for driving future colliders. This work was stimulated by a recent request of SLAC to develop high power, high-efficiency sources of sub-THz radiation for future high-gradient accelerators.

Identification of the numerical model of FEM in reference to measurements in situ

Science.gov (United States)

Jukowski, Michał; Bec, Jarosław; Błazik-Borowa, Ewa

2018-01-01

The paper deals with the verification of various numerical models in relation to the pilot-phase measurements of a rail bridge subjected to dynamic loading. Three types of FEM models were elaborated for this purpose. Static, modal and dynamic analyses were performed. The study consisted of measuring the acceleration values of the structural components of the object at the moment of the train passing. Based on this, FFT analysis was performed, the main natural frequencies of the bridge were determined, the structural damping ratio and the dynamic amplification factor (DAF) were calculated and compared with the standard values. Calculations were made using Autodesk Simulation Multiphysics (Algor).

Dataset of the human homologues and orthologues of lipid-metabolic genes identified as DAF-16 targets their roles in lipid and energy metabolism

Directory of Open Access Journals (Sweden)

Lavender Yuen-Nam Fan

2017-04-01

Full Text Available The data presented in this article are related to the review article entitled ‘Unravelling the role of fatty acid metabolism in cancer through the FOXO3-FOXM1 axis’ (Saavedra-Garcia et al., 2017 [24]. Here, we have matched the DAF-16/FOXO3 downstream genes with their respective human orthologues and reviewed the roles of these targeted genes in FA metabolism. The list of genes listed in this article are precisely selected from literature reviews based on their functions in mammalian FA metabolism. The nematode Caenorhabditis elegans gene orthologues of the genes are obtained from WormBase, the online biological database of C. elegans. This dataset has not been uploaded to a public repository yet.

Susceptibility of materials processing experiments to low-level accelerations

Science.gov (United States)

Naumann, R. J.

1981-01-01

The types of material processing experiments being considered for shuttle can be grouped into four categories: (1) contained solidification experiment; (2) quasicontainerless experiments; (3) containerless experiments; and (4) fluids experiments. Low level steady acceleration, compensated and uncompensated transient accelerations, and rotation induced flow factors that must be considered in the acceleration environment of a space vehicle whose importance depends on the type of experiment being performed. Some control of these factors may be exercised by the location and orientation of the experiment relative to shuttle and by the orbit vehicle attitude chosen for mission. The effects of the various residual accelerations can have serious consequence to the control of the experiment and must be factored into the design and operation of the apparatus.

Generalized Coarse-Mesh Rebalance Method for Acceleration of Neutron Transport Calculations

International Nuclear Information System (INIS)

Yamamoto, Akio

2005-01-01

This paper proposes a new acceleration method for neutron transport calculations: the generalized coarse-mesh rebalance (GCMR) method. The GCMR method is a unified scheme of the traditional coarse-mesh rebalance (CMR) and the coarse-mesh finite difference (CMFD) acceleration methods. Namely, by using an appropriate acceleration factor, formulation of the GCMR method becomes identical to that of the CMR or CMFD method. This also indicates that the convergence property of the GCMR method can be controlled by the acceleration factor since the convergence properties of the CMR and CMFD methods are generally different. In order to evaluate the convergence property of the GCMR method, a linearized Fourier analysis was carried out for a one-group homogeneous medium, and the results clarified the relationship between the acceleration factor and the spectral radius. It was also shown that the spectral radius of the GCMR method is smaller than those of the CMR and CMFD methods. Furthermore, the Fourier analysis showed that when an appropriate acceleration factor was used, the spectral radius of the GCMR method did not exceed unity in this study, which was in contrast to the results of the CMR or the CMFD method. Application of the GCMR method to practical calculations will be easy when the CMFD acceleration is already adopted in a transport code. By multiplying a suitable acceleration factor to a coefficient (D FD ) of a finite difference formulation, one can improve the numerical instability of the CMFD acceleration method

Design of the detuned accelerator structure

International Nuclear Information System (INIS)

Wang, J.W.; Nelson, E.M.

1993-05-01

This is a summary of the design procedure for the detuned accelerator structure for SLAC's Next Linear Collider (NLC) program. The 11.424 GHz accelerating mode of each cavity must be synchronous with the beam. The distribution of the disk thicknesses and lowest synchronous dipole mode frequencies of the cavities in the structure is Gaussian in order to reduce the effect of wake fields. The finite element field solver YAP calculated the accelerating mode frequency and the lowest synchronous dipole mode frequency for various cavity diameters, aperture diameters and disk thicknesses. Polynomial 3-parameter fits are used to calculate the dimensions for a 1.8 m detuned structure. The program SUPERFISH was used to calculate the shunt impedances, quality factors and group velocities. The RF parameters of the section like filling time, attenuation factor, accelerating gradient and maximum surface field along the section are evaluated. Error estimates will be discussed and comparisons with conventional constant gradient and constant impedance structures will be presented

Branched-chain amino acid catabolism is a conserved regulator of physiological ageing.

Science.gov (United States)

Mansfeld, Johannes; Urban, Nadine; Priebe, Steffen; Groth, Marco; Frahm, Christiane; Hartmann, Nils; Gebauer, Juliane; Ravichandran, Meenakshi; Dommaschk, Anne; Schmeisser, Sebastian; Kuhlow, Doreen; Monajembashi, Shamci; Bremer-Streck, Sibylle; Hemmerich, Peter; Kiehntopf, Michael; Zamboni, Nicola; Englert, Christoph; Guthke, Reinhard; Kaleta, Christoph; Platzer, Matthias; Sühnel, Jürgen; Witte, Otto W; Zarse, Kim; Ristow, Michael

2015-12-01

Ageing has been defined as a global decline in physiological function depending on both environmental and genetic factors. Here we identify gene transcripts that are similarly regulated during physiological ageing in nematodes, zebrafish and mice. We observe the strongest extension of lifespan when impairing expression of the branched-chain amino acid transferase-1 (bcat-1) gene in C. elegans, which leads to excessive levels of branched-chain amino acids (BCAAs). We further show that BCAAs reduce a LET-363/mTOR-dependent neuro-endocrine signal, which we identify as DAF-7/TGFβ, and that impacts lifespan depending on its related receptors, DAF-1 and DAF-4, as well as ultimately on DAF-16/FoxO and HSF-1 in a cell-non-autonomous manner. The transcription factor HLH-15 controls and epistatically synergizes with BCAT-1 to modulate physiological ageing. Lastly and consistent with previous findings in rodents, nutritional supplementation of BCAAs extends nematodal lifespan. Taken together, BCAAs act as periphery-derived metabokines that induce a central neuro-endocrine response, culminating in extended healthspan.

Using Uncertainty Analysis to Guide the Development of Accelerated Stress Tests (Presentation)

Energy Technology Data Exchange (ETDEWEB)

Kempe, M.

2014-03-01

Extrapolation of accelerated testing to the long-term results expected in the field has uncertainty associated with the acceleration factors and the range of possible stresses in the field. When multiple stresses (such as temperature and humidity) can be used to increase the acceleration, the uncertainty may be reduced according to which stress factors are used to accelerate the degradation.

Identification of key factors in Accelerated Low Water Corrosion through experimental simulation of tidal conditions: influence of stimulated indigenous microbiota

NARCIS (Netherlands)

Marty, F.; Gueuné, H.; Malard, E.; Sánchez-Amaya, J.M.; Sjögren, L.; Abbas, B.; Quillet, L.; van Loosdrecht, M.C.M.; Muyzer, G.

2014-01-01

Biotic and abiotic factors favoring Accelerated Low Water Corrosion (ALWC) on harbor steel structures remain unclear warranting their study under controlled experimental tidal conditions. Initial stimulation of marine microbial consortia by a pulse of organic matter resulted in localized corrosion

Molecular characterisation of Colombian yam germplasm by "DNA amplification fingerprinting (DAF" in radioactivo conditions Caracterización molecular del germoplasma de ñame colombiano utilizando "DNA Amplificaron Fingerprinting (DAF" en condiciones radiactivas

Directory of Open Access Journals (Sweden)

Bustamante Silvia L.

2003-12-01

Full Text Available Samples from the Universidad de Córdoba's yam collection (Dioscorea spp. and others originating from IITA (International Institute of Tropical Agriculture, Ibadan, Nigeria were molecularly characterised to complement existing information about them. The yam (Diosocorea spp. represents a basic crop for small-scale farmers on the Colombian Atlantic Coast who sow around 20,000 hectares per year. Even though they are dioecious species, only one sex is represented in Colombia; it must also be stated that climatic conditions are not propitious for its flowering. This situation has caused difficulty for work in yam breeding. The yam species and varieties used in the Colombian ABP (Agricultural Biotechnology Programme have been molecularly characterised by AFLPs in a previous publication describing a preliminary study emerging from the need to broaden the characterisation of those accessions kept at the Universidad de Córdoba. Comparisons have also been done with some African accessions donated by IITA. In this article, samples were molecularly characterised by another fingerprinting technique, the DAF technique (DNA Amplification Fingerprinting based on PCR, using random oligonucleotides for generating characteristic band patterns from each individual. The results showed 0.0413 population diversity with 0.9587 average similarity, indicating that the yam collection studied had very little genetic diversity and, probably, this could be why the crop is vulnerable to plagues and diseases, as happened at the end of the 1980s when anthracnose practically devastated the crop on the Colombian Atlantic coast. Similarity was also found between those Colombian and African samples analysed, agreeing with low diversity and less distance between common ancestors. The molecular results suggest the need for using other molecular techniques having a greater power of discrimination and also the need to broaden the genetic diversity in yam crops for providing greater

Linear Accelerator Stereotactic Radiosurgery of Central Nervous System Arteriovenous Malformations: A 15-Year Analysis of Outcome-Related Factors in a Single Tertiary Center.

Science.gov (United States)

Thenier-Villa, José Luis; Galárraga-Campoverde, Raúl Alejandro; Martínez Rolán, Rosa María; De La Lama Zaragoza, Adolfo Ramón; Martínez Cueto, Pedro; Muñoz Garzón, Víctor; Salgado Fernández, Manuel; Conde Alonso, Cesáreo

2017-07-01

Linear accelerator stereotactic radiosurgery is one of the modalities available for the treatment of central nervous system arteriovenous malformations (AVMs). The aim of this study was to describe our 15-year experience with this technique in a single tertiary center and the analysis of outcome-related factors. From 1998 to 2013, 195 patients were treated with linear accelerator-based radiosurgery; we conducted a retrospective study collecting patient- and AVM-related variables. Treatment outcomes were obliteration, posttreatment hemorrhage, symptomatic radiation-induced changes, and 3-year neurologic status. We also analyzed prognostic factors of each outcome and predictability analysis of 5 scales: Spetzler-Martin grade, Lawton-Young supplementary and Lawton combined scores, radiosurgery-based AVM score, Virginia Radiosurgery AVM Scale, and Heidelberg score. Overall obliteration rate was 81%. Nidus diameter and venous drainage were predictive of obliteration (P linear accelerator-based radiosurgery is a useful, valid, effective, and safe modality for treatment of brain AVMs. Copyright © 2017 Elsevier Inc. All rights reserved.

Brain-Derived Neurotrophic Factor Expression in Individuals With Schizophrenia and Healthy Aging: Testing the Accelerated Aging Hypothesis of Schizophrenia.

Science.gov (United States)

Islam, Farhana; Mulsant, Benoit H; Voineskos, Aristotle N; Rajji, Tarek K

2017-07-01

Schizophrenia has been hypothesized to be a syndrome of accelerated aging. Brain plasticity is vulnerable to the normal aging process and affected in schizophrenia: brain-derived neurotrophic factor (BDNF) is an important neuroplasticity molecule. The present review explores the accelerated aging hypothesis of schizophrenia by comparing changes in BDNF expression in schizophrenia with aging-associated changes. Individuals with schizophrenia show patterns of increased overall mortality, metabolic abnormalities, and cognitive decline normally observed later in life in the healthy population. An overall decrease is observed in BDNF expression in schizophrenia compared to healthy controls and in older individuals compared to a younger cohort. There is a marked decrease in BDNF levels in the frontal regions and in the periphery among older individuals and those with schizophrenia; however, data for BDNF expression in the occipital, parietal, and temporal cortices and the hippocampus is inconclusive. Accelerated aging hypothesis is supported based on frontal regions and peripheral studies; however, further studies are needed in other brain regions.

Research of the influencing factors of the immobilized redox mediators accelerating Cr(Ⅵ reduction by Escherichia coli BL21

Directory of Open Access Journals (Sweden)

Jiapeng PING

2017-10-01

Full Text Available In order to study the influencing factors of non-dissolved redox mediators on Cr (Ⅵ bioreduction, the accelerating effect of non-dissolved redox mediators immobilized by cellulose acetate (CA on the reduction of Cr(Ⅵ by Escherichia coli BL21 is investigated. The results show that the accelerating order is 1-chloroanthraquinone>1,5-dichloroanthraquinone>2-chloroanthraquinone>1,8-dichloroanthraquinone>anthraquinone>1,4,5,8-tetrachloroanthtaquinone; the optimal concentration of 1-chloroanthraquinone pH and initial Cr(Ⅵ concentration are 0.048 mol/L, 7.00 and 30 mg/L, respectively; the removal rate increases with the increasing temperature when it is in the range of 20~60 ℃; after 6 times of recycling experiments, and the Cr(Ⅵ bioreduction rate with the immobilized 1-chloroanthraquinone maintains above 5 times of margin bacterium's. It indicates that non-dissolved redox mediators immobilized by CA can effectively accelerate the reduction rate of Cr(Ⅵ by Escherichia coli BL21, which has favourable application value.

PDP-1 links the TGF-β and IIS pathways to regulate longevity, development, and metabolism.

Directory of Open Access Journals (Sweden)

Sri Devi Narasimhan

2011-04-01

Full Text Available The insulin/IGF-1 signaling (IIS pathway is a conserved regulator of longevity, development, and metabolism. In Caenorhabditis elegans IIS involves activation of DAF-2 (insulin/IGF-1 receptor tyrosine kinase, AGE-1 (PI 3-kinase, and additional downstream serine/threonine kinases that ultimately phosphorylate and negatively regulate the single FOXO transcription factor homolog DAF-16. Phosphatases help to maintain cellular signaling homeostasis by counterbalancing kinase activity. However, few phosphatases have been identified that negatively regulate the IIS pathway. Here we identify and characterize pdp-1 as a novel negative modulator of the IIS pathway. We show that PDP-1 regulates multiple outputs of IIS such as longevity, fat storage, and dauer diapause. In addition, PDP-1 promotes DAF-16 nuclear localization and transcriptional activity. Interestingly, genetic epistasis analyses place PDP-1 in the DAF-7/TGF-β signaling pathway, at the level of the R-SMAD proteins DAF-14 and DAF-8. Further investigation into how a component of TGF-β signaling affects multiple outputs of IIS/DAF-16, revealed extensive crosstalk between these two well-conserved signaling pathways. We find that PDP-1 modulates the expression of several insulin genes that are likely to feed into the IIS pathway to regulate DAF-16 activity. Importantly, dysregulation of IIS and TGF-β signaling has been implicated in diseases such as Type 2 Diabetes, obesity, and cancer. Our results may provide a new perspective in understanding of the regulation of these pathways under normal conditions and in the context of disease.

Control of electron injection and acceleration in laser-wakefield accelerators

International Nuclear Information System (INIS)

Guillaume, E.

2015-01-01

Laser-plasma accelerators provide a promising compact alternative to conventional accelerators. Plasma waves with extremely strong electric fields are generated when a high intensity laser is focused into an underdense gas target. Electrons that are trapped in these laser-driven plasma waves can be accelerated up to energies of a few GeVs. Despite their great potential, laser-wakefield accelerators face some issues, regarding notably the stability and reproducibility of the beam when electrons are injected in the accelerating structure. In this manuscript, different techniques of electron injection are presented and compared, notably injection in a sharp density gradient and ionization injection. It is shown that combining these two methods allows for the generation of stable and tunable electron beams. We have also studied a way to manipulate the electron bunch in the phase-space in order to accelerate the bunch beyond the dephasing limit. Such a technique was used with quasi-monoenergetic electron beams to enhance their energy. Moreover, the origin of the evolution of the angular momentum of electrons observed experimentally was investigated. Finally, we demonstrated experimentally a new method - the laser-plasma lens - to strongly reduce the divergence of the electron beam. This laser-plasma lens consists of a second gas jet placed at the exit of the accelerator. The laser pulse drives a wakefield in this second jet whose focusing forces take advantage to reduce the divergence of the trailing electron bunch. A simple analytical model describing the principle is presented, underlining the major importance of the second jet length, density and distance from the first jet. Experimental demonstration of the laser-plasma lens shows a divergence reduction by a factor of 2.6 for electrons up to 300 MeV, in accordance with the model predictions

Optimizing conditions for an accelerated leach test

International Nuclear Information System (INIS)

Pietrzak, R.F.; Fuhrmann, M.; Heiser, J.; Franz, E.M.; Colombo, P.

1988-01-01

An accelerated leach test for low-level radioactive waste forms is being developed to provide, in a short time, data that can be extrapolated to long time periods. The approach is to provide experimental conditions that will accelerate leaching without changing the dominant release mechanism. Experimental efforts have focused on combining individual factors that have been observed to accelerate leaching. These include elevated temperature, increased leachant volume, and reduced specimen size. The response of diffusion coefficients to various acceleration factors have been evaluated and provide information on experimental parameters that need to be optimized to increase leach rates. Preliminary modeling using a diffusion mechanism (allowing for depletion) of a finite cylinder geometry indicates that during early portions of experiments (daily sampling intervals), leaching is diffusion controlled and more rapid than later in the same experiments (weekly or greater sampling intervals). For cement waste forms, this reduction in rate may be partially controlled by changes in physical structure and chemistry (sometimes related to environmental influences such as CO 2 ), but it is more likely associated with the duration of the sampling interval. By using a combination of mathematical modeling and by experimentally investigating various leach rate controlling factors, a more complete understanding of leaching processes is being developed. This, in turn, is leading to optimized accelerating conditions for a leach test

Dynamics of electron acceleration in laser-driven wakefields. Acceleration limits and asymmetric plasma waves

Energy Technology Data Exchange (ETDEWEB)

Popp, Antonia

2011-12-16

The experiments presented in this thesis study several aspects of electron acceleration in a laser-driven plasma wave. High-intensity lasers can efficiently drive a plasma wave that sustains electric fields on the order of 100 GV/m. Electrons that are trapped in this plasma wave can be accelerated to GeV-scale energies. As the accelerating fields in this scheme are 3-4 orders of magnitude higher than in conventional radio-frequency accelerators, the necessary acceleration distance can be reduced by the same factor, turning laser-wakefield acceleration (LWFA) into a promising compact, and potentially cheaper, alternative. However, laser-accelerated electron bunches have not yet reached the parameter standards of conventional accelerators. This work will help to gain better insight into the acceleration process and to optimize the electron bunch properties. The 25 fs, 1.8 J-pulses of the ATLAS laser at the Max-Planck-Institute of Quantum Optics were focused into a steady-state flow gas cell. This very reproducible and turbulence-free gas target allows for stable acceleration of electron bunches. Thus the sensitivity of electron parameters to subtle changes of the experimental setup could be determined with meaningful statistics. At optimized experimental parameters, electron bunches of {approx}50 pC total charge were accelerated to energies up to 450 MeV with a divergence of {approx}2 mrad FWHM. As, in a new design of the gas cell, its length can be varied from 2 to 14 mm, the electron bunch energy could be evaluated after different acceleration distances, at two different electron densities. From this evolution important acceleration parameters could be extracted. At an electron density of 6.43. 10{sup 18} cm{sup -3} the maximum electric field strength in the plasma wave was determined to be {approx}160 GV/m. The length after which the relativistic electrons outrun the accelerating phase of the electric field and are decelerated again, the so-called dephasing length

Dynamics of electron acceleration in laser-driven wakefields. Acceleration limits and asymmetric plasma waves

International Nuclear Information System (INIS)

Popp, Antonia

2011-01-01

The experiments presented in this thesis study several aspects of electron acceleration in a laser-driven plasma wave. High-intensity lasers can efficiently drive a plasma wave that sustains electric fields on the order of 100 GV/m. Electrons that are trapped in this plasma wave can be accelerated to GeV-scale energies. As the accelerating fields in this scheme are 3-4 orders of magnitude higher than in conventional radio-frequency accelerators, the necessary acceleration distance can be reduced by the same factor, turning laser-wakefield acceleration (LWFA) into a promising compact, and potentially cheaper, alternative. However, laser-accelerated electron bunches have not yet reached the parameter standards of conventional accelerators. This work will help to gain better insight into the acceleration process and to optimize the electron bunch properties. The 25 fs, 1.8 J-pulses of the ATLAS laser at the Max-Planck-Institute of Quantum Optics were focused into a steady-state flow gas cell. This very reproducible and turbulence-free gas target allows for stable acceleration of electron bunches. Thus the sensitivity of electron parameters to subtle changes of the experimental setup could be determined with meaningful statistics. At optimized experimental parameters, electron bunches of ∼50 pC total charge were accelerated to energies up to 450 MeV with a divergence of ∼2 mrad FWHM. As, in a new design of the gas cell, its length can be varied from 2 to 14 mm, the electron bunch energy could be evaluated after different acceleration distances, at two different electron densities. From this evolution important acceleration parameters could be extracted. At an electron density of 6.43. 10 18 cm -3 the maximum electric field strength in the plasma wave was determined to be ∼160 GV/m. The length after which the relativistic electrons outrun the accelerating phase of the electric field and are decelerated again, the so-called dephasing length, was found to be 4.9 mm

Disruption of insulin signalling preserves bioenergetic competence of mitochondria in ageing Caenorhabditis elegans

Directory of Open Access Journals (Sweden)

Vanfleteren Jacques R

2010-06-01

Full Text Available Abstract Background The gene daf-2 encodes the single insulin/insulin growth factor-1-like receptor of Caenorhabditis elegans. The reduction-of-function allele e1370 induces several metabolic alterations and doubles lifespan. Results We found that the e1370 mutation alters aerobic energy production substantially. In wild-type worms the abundance of key mitochondrial proteins declines with age, accompanied by a dramatic decrease in energy production, although the mitochondrial mass, inferred from the mitochondrial DNA copy number, remains unaltered. In contrast, the age-dependent decrease of both key mitochondrial proteins and bioenergetic competence is considerably attenuated in daf-2(e1370 adult animals. The increase in daf-2(e1370 mitochondrial competence is associated with a higher membrane potential and increased reactive oxygen species production, but with little damage to mitochondrial protein or DNA. Together these results point to a higher energetic efficiency of daf-2(e1370 animals. Conclusions We conclude that low daf-2 function alters the overall rate of ageing by a yet unidentified mechanism with an indirect protective effect on mitochondrial function.

Electron accelerator technology research in food irradiation

International Nuclear Information System (INIS)

Jin Jianqiao; Ye Mingyang; Zhang Yue; Yang Bin; Xu Tao; Kong Xiangshan

2014-01-01

Electronic accelerator was applied to instead of cobalt sources for food irradiation, to keep food quality and to improve the effect of the treatment. Appropriate accelerator parameters lead to optimal technique. The irradiation effect is associated with the relationship between uniformity and irradiating speed, the effect of cargo size on radiation penetration, as well as other factors that affect the irradiation effects. Industrialization of electron accelerator irradiation will be looked to the future. (authors)

Does the magnetic expansion factor (fs) play a role in solar wind acceleration?

Science.gov (United States)

Wallace, Samantha; Arge, Charles N.; Pihlstrom, Ylva

2017-08-01

For the past 25 years, magnetic expansion factor (fs) has been a key parameter used in the calculation of terminal solar wind speed (vsw) in both the Wang-Sheeley-Arge (WSA) model and its predecessor the Wang-Sheeley (WS) model. Since the discovery of an inverse relationship between fs and vsw, the physical role that magnetic expansion factor plays in the acceleration of the solar wind has been explored and debated. In this study, we investigate whether magnetic expansion factor plays a causal role in determining the terminal speed of the solar wind or merely serves as proxy. To do so, we explore how fs, as determined by WSA, relates to vsw for two different scenarios: 1) extended periods where the fast solar wind emerges from the centers of large coronal holes, and 2) periods where the solar wind emerges from pseudostreamers. For these same scenarios, we will also consider an alternative empirical relationship between solar wind speed and the minimum angular distance at the photosphere of a solar wind source to the nearest coronal hole boundary (i.e., DCHB, θb). We then compare these two different prediction techniques directly with heliospheric observations (i.e., ACE, STEREO-A & B, Ulysses) of solar wind speed to determine whether one clearly out performs the other.

Measurement and correction of accelerator optics

International Nuclear Information System (INIS)

Zimmerman, F.

1998-06-01

This report reviews procedures and techniques for measuring, correcting and controlling various optics parameters of an accelerator, including the betatron tune, beta function, betatron coupling, dispersion, chromaticity, momentum compaction factor, and beam orbit. The techniques described are not only indispensable for the basic set-up of an accelerator, but in addition the same methods can be used to study more esoteric questions as, for instance, dynamic aperture limitations or wakefield effects. The different procedures are illustrated by examples from several accelerators, storage rings, as well as linacs and transport lines

Unprecedented quality factors at accelerating gradients up to 45 MVm-1 in niobium superconducting resonators via low temperature nitrogen infusion

Science.gov (United States)

Grassellino, A.; Romanenko, A.; Trenikhina, Y.; Checchin, M.; Martinello, M.; Melnychuk, O. S.; Chandrasekaran, S.; Sergatskov, D. A.; Posen, S.; Crawford, A. C.; Aderhold, S.; Bice, D.

2017-09-01

We report the finding of new surface treatments that permits one to manipulate the niobium resonator nitrogen content in the first few nanometers in a controlled way, and the resonator fundamental Mattis-Bardeen surface resistance and residual resistance accordingly. In particular, we find surface ‘infusion’ conditions that systematically (a) increase the quality factor of these 1.3 GHz superconducting radio frequency (SRF) bulk niobium resonators, up to very high gradients; (b) increase the achievable accelerating gradient of the cavity compared to its own baseline with state-of-the-art surface processing. Cavities subject to the new surface process have more than two times the state-of-the-art Q at 2 K for accelerating fields >35 MVm-1. Moreover, very high accelerating gradients ˜45 MVm-1 are repeatedly reached, which correspond to peak magnetic surface fields of 190 mT, among the highest measured for bulk niobium cavities. These findings open the opportunity to tailor the surface impurity content distribution to maximize performance in Q and gradients, and have therefore very important implications on future performance and cost of SRF based accelerators. They also help deepen the understanding of the physics of the RF niobium cavity surface.

Commissioning measurements for photon beam data on three TrueBeam linear accelerators, and comparison with Trilogy and Clinac 2100 linear accelerators

Science.gov (United States)

2013-01-01

This study presents the beam data measurement results from the commissioning of three TrueBeam linear accelerators. An additional evaluation of the measured beam data within the TrueBeam linear accelerators contrasted with two other linear accelerators from the same manufacturer (i.e., Clinac and Trilogy) was performed to identify and evaluate any differences in the beam characteristics between the machines and to evaluate the possibility of beam matching for standard photon energies. We performed a comparison of commissioned photon beam data for two standard photon energies (6 MV and 15 MV) and one flattening filter‐free (“FFF”) photon energy (10 FFF) between three different TrueBeam linear accelerators. An analysis of the beam data was then performed to evaluate the reproducibility of the results and the possibility of “beam matching” between the TrueBeam linear accelerators. Additionally, the data from the TrueBeam linear accelerator was compared with comparable data obtained from one Clinac and one Trilogy linear accelerator models produced by the same manufacturer to evaluate the possibility of “beam matching” between the TrueBeam linear accelerators and the previous models. The energies evaluated between the linear accelerator models are the 6 MV for low energy and the 15 MV for high energy. PDD and output factor data showed less than 1% variation and profile data showed variations within 1% or 2 mm between the three TrueBeam linear accelerators. PDD and profile data between the TrueBeam, the Clinac, and Trilogy linear accelerators were almost identical (less than 1% variation). Small variations were observed in the shape of the profile for 15 MV at shallow depths (linear accelerators; the TrueBeam data resulted in a slightly greater penumbra width. The diagonal scans demonstrated significant differences in the profile shapes at a distance greater than 20 cm from the central axis, and this was more notable for the 15 MV energy. Output factor

Reduced Insulin/Insulin-like Growth Factor-1 Signaling and Dietary Restriction Inhibit Translation but Preserve Muscle Mass in Caenorhabditis elegans

Energy Technology Data Exchange (ETDEWEB)

Depuydt, Geert; Xie, Fang; Petyuk, Vladislav A.; Shanmugam, Nilesh; Smolders, Arne; Dhondt, Ineke; Brewer, Heather M.; Camp, David G.; Smith, Richard D.; Braeckman, Bart P.

2013-09-03

Reduced signaling through the C. elegans insulin/IGF1 like tyrosine kinase receptor daf2 and dietary restriction via bacterial dilution are two well-characterized lifespan-extending interventions that operate in parallel or through (partially) independent mechanisms. Using accurate mass and time tag LCMS/MS quantitative proteomics we detected that the abundance of a large number of ribosomal subunits is decreased in response to dietary restriction as well as in the daf2(e1370) insulin/IGF1 receptor mutant. In addition, general protein synthesis levels in these long-lived worms are repressed. Surprisingly, ribosomal transcript levels were not correlated to actual protein abundance, suggesting that posttranscriptional regulation determines ribosome content. Proteomics also revealed increased presence of many structural muscle cell components in long-lived worms, which appears to result from prioritized preservation of muscle cell volume in nutrient-poor conditions or low insulin-like signaling. Activation of DAF16, but not diet-restriction, stimulates mRNA expression of muscle-related genes to prevent muscle atrophy. Important daf2 specific proteome changes include overexpression of aerobic metabolism enzymes and a general activation of stress responsive and immune defense systems, while increased abundance of many protein subunits of the proteasome core complex is a DR-specific characteristic.

The Path to High Q-Factors in Superconducting Accelerating Cavities: Flux Expulsion and Surface Resistance Optimization

Energy Technology Data Exchange (ETDEWEB)

Martinello, Martina [Illinois Inst. of Technology, Chicago, IL (United States)

2016-12-01

Accelerating cavities are devices resonating in the radio-frequency (RF) range used to accelerate charged particles in accelerators. Superconducting accelerating cavities are made out of niobium and operate at the liquid helium temperature. Even if superconducting, these resonating structures have some RF driven surface resistance that causes power dissipation. In order to decrease as much as possible the power losses, the cavity quality factor must be increased by decreasing the surface resistance. In this dissertation, the RF surface resistance is analyzed for a large variety of cavities made with different state-of-the-art surface treatments, with the goal of finding the surface treatment capable to return the highest Q-factor values in a cryomodule-like environment. This study analyzes not only the superconducting properties described by the BCS surface resistance, which is the contribution that takes into account dissipation due to quasi-particle excitations, but also the increasing of the surface resistance due to trapped flux. When cavities are cooled down below their critical temperature inside a cryomodule, there is always some remnant magnetic field that may be trapped increasing the global RF surface resistance. This thesis also analyzes how the fraction of external magnetic field, which is actually trapped in the cavity during the cooldown, can be minimized. This study is performed on an elliptical single-cell horizontally cooled cavity, resembling the geometry of cavities cooled in accelerator cryomodules. The horizontal cooldown study reveals that, as in case of the vertical cooldown, when the cooling is performed fast, large thermal gradients are created along the cavity helping magnetic flux expulsion. However, for this geometry the complete magnetic flux expulsion from the cavity equator is more difficult to achieve. This becomes even more challenging in presence of orthogonal magnetic field, that is easily trapped on top of the cavity equator

The path to high Q-factors in superconducting accelerating cavities: Flux expulsion and surface resistance optimization

Science.gov (United States)

Martinello, Martina

Accelerating cavities are devices resonating in the radio-frequency (RF) range used to accelerate charged particles in accelerators. Superconducting accelerating cavities are made out of niobium and operate at the liquid helium temperature. Even if superconducting, these resonating structures have some RF driven surface resistance that causes power dissipation. In order to decrease as much as possible the power losses, the cavity quality factor must be increased by decreasing the surface resistance. In this dissertation, the RF surface resistance is analyzed for a large variety of cavities made with different state-of-the-art surface treatments, with the goal of finding the surface treatment capable to return the highest Q-factor values in a cryomodule-like environment. This study analyzes not only the superconducting properties described by the BCS surface resistance, which is the contribution that takes into account dissipation due to quasi-particle excitations, but also the increasing of the surface resistance due to trapped flux. When cavities are cooled down below their critical temperature inside a cryomodule, there is always some remnant magnetic field that may be trapped increasing the global RF surface resistance. This thesis also analyzes how the fraction of external magnetic field, which is actually trapped in the cavity during the cooldown, can be minimized. This study is performed on an elliptical single-cell horizontally cooled cavity, resembling the geometry of cavities cooled in accelerator cryomodules. The horizontal cooldown study reveals that, as in case of the vertical cooldown, when the cooling is performed fast, large thermal gradients are created along the cavity helping magnetic flux expulsion. However, for this geometry the complete magnetic flux expulsion from the cavity equator is more difficult to achieve. This becomes even more challenging in presence of orthogonal magnetic field, that is easily trapped on top of the cavity equator

Laser-driven acceleration with Bessel and Gaussian beams

International Nuclear Information System (INIS)

Hafizi, B.; Esarey, E.; Sprangle, P.

1997-01-01

The possibility of enhancing the energy gain in laser-driven accelerators by using Bessel laser beams is examined. Scaling laws are derived for the propagation length, acceleration gradient, and energy gain in various accelerators for both Gaussian and Bessel beam drivers. For equal beam powers, the energy gain can be increased by a factor of N 1/2 by utilizing a Bessel beam with N lobes, provided that the acceleration gradient is linearly proportional to the laser field. This is the case in the inverse free electron laser and the inverse Cherenkov accelerators. If the acceleration gradient is proportional to the square of the laser field (e.g., the laser wakefield, plasma beat wave, and vacuum beat wave accelerators), the energy gain is comparable with either beam profile. copyright 1997 American Institute of Physics

Licensing criteria for particle accelerators categorization

International Nuclear Information System (INIS)

Costa, Evaldo L.C. da

2013-01-01

From the international experience of research centers in various parts of the world, where there are particle accelerators of various sizes and energies, it was found that operating energy of particle accelerators is one of the parameters used by categorization models in the licensing of these radiation facilities, and the facility size is an important aspect to be considered in this model. A categorization based on these two key parameters is presented, also taking into account the kinds of accelerated particles and radiation produced, the operating related technology and the possible applications concerned. The categorization models of national nuclear authorities of five countries are reviewed, emphasizing the contribution of Brazil, and the new model proposed is also based on the experience of these countries, modified by those two parameter discussed above: facility size and operating energy of particle accelerators. Later, some changes are suggested, considering risk factors and safety features related to these facilities, emphasizing some analytical tools commonly used in nuclear facilities and chemical plants, such as: risk-informing decision making, layer of protection analysis (LOPRA) and safety integrity levels (SIL), the two latter ones having its origin in the broader concept of system safety. We also discuss the problem of scarcity of reliability data (common in the analyses involving risk factors and safety), due to security concerns and other factors, being the possible alternative solutions the use of generic databases and the adoption of reference facilities that provide partial data publicly. (author).

Licensing criteria for particle accelerators categorization

Energy Technology Data Exchange (ETDEWEB)

Costa, Evaldo L.C. da, E-mail: evaldo@cnen.gov.br [Comissao Nacional de Energia Nuclear (CNEN-RJ), Rio de Janeiro, RJ (Brazil). Dir. de Radioprotecao e Seguranca; Melo, Paulo F.F. Frutuoso e, E-mail: frutuoso@nuclear.ufrj.br [Coordenacao dos Programas de Pos-Graduacao em Engenharia (COPPE/UFRJ), Rio de Janeiro, RJ (Brazil)

2013-07-01

From the international experience of research centers in various parts of the world, where there are particle accelerators of various sizes and energies, it was found that operating energy of particle accelerators is one of the parameters used by categorization models in the licensing of these radiation facilities, and the facility size is an important aspect to be considered in this model. A categorization based on these two key parameters is presented, also taking into account the kinds of accelerated particles and radiation produced, the operating related technology and the possible applications concerned. The categorization models of national nuclear authorities of five countries are reviewed, emphasizing the contribution of Brazil, and the new model proposed is also based on the experience of these countries, modified by those two parameter discussed above: facility size and operating energy of particle accelerators. Later, some changes are suggested, considering risk factors and safety features related to these facilities, emphasizing some analytical tools commonly used in nuclear facilities and chemical plants, such as: risk-informing decision making, layer of protection analysis (LOPRA) and safety integrity levels (SIL), the two latter ones having its origin in the broader concept of system safety. We also discuss the problem of scarcity of reliability data (common in the analyses involving risk factors and safety), due to security concerns and other factors, being the possible alternative solutions the use of generic databases and the adoption of reference facilities that provide partial data publicly. (author).

Formation and acceleration of precompressed compact tori in RACE

International Nuclear Information System (INIS)

Molvik, A.W.; Eddleman, J.L.; Hammer, J.H.; Hartman, C.W.; McLean, H.S.

1990-01-01

Many applications of the compact torus accelerator, CTA, concept (such as a driver for inertial fusion, or magnetically insulated inertial fusion) require maximizing the power density by compressing the compact torus, CT. The ring accelerator experiment, RACE, has compressed CT's by a factor of 2 in radius before acceleration, after being reconfigured with a precompressor cone followed by a short, 80 cm long, coaxial accelerator. The authors show the gas valves and gun, precompressor, and the beginning of the accelerator. The inner acceleration electrode begins at the precompressor cone after passing through the inner gun electrode. The authors discuss the experimental results of slow formation, compression, and acceleration in this new geometry

Prowashonupana barley dietary fibre reduces body fat and increases insulin sensitivity in Caenorhabditis elegans model

Science.gov (United States)

Gao, Chenfei; King, Michael L.; Fitzpatrick, Zachary L.; Wei, Wenqian; King, Jason F.; Wang, Mingming; Greenway, Frank L.; Finley, John W.; Burton, Jeffrey H.; Johnson, William D.; Keenan, Michael J.; Enright, Frederick M.; Martin, Roy J.; Zheng, Jolene

2016-01-01

Prowashonupana barley (PWB) is high in β-glucan with moderate content of resistant starch. PWB reduced intestinal fat deposition (IFD) in wild type Caenorhabditis elegans (C. elegans, N2), and in sir-2.1 or daf-16 null mutants, and sustained a surrogate marker of lifespan, pharyngeal pumping rate (PPR), in N2, sir-2.1, daf-16, or daf-16/daf-2 mutants. Hyperglycaemia (2% glucose) reversed or reduced the PWB effect on IFD in N2 or daf-16/daf-2 mutants with a sustained PPR. mRNA expression of cpt-1, cpt-2, ckr-1, and gcy-8 were dose-dependently reduced in N2 or daf-16 mutants, elevated in daf-16/daf-2 mutants with reduction in cpt-1, and unchanged in sir-2.1 mutants. mRNA expressions were increased by hyperglycaemia in N2 or daf-16/daf-2 mutants, while reduced in sir-2.1 or daf-16 mutants. The effects of PWB in the C. elegans model appeared to be primarily mediated via sir-2.1, daf-16, and daf-16/daf-2. These data suggest that PWB and β-glucans may benefit hyperglycaemia-impaired lipid metabolism. PMID:27721901

Effects of acceleration through the Dirac sea

International Nuclear Information System (INIS)

Hacyan, S.

1986-01-01

The effects of acceleration through massive scalar and spin-1/2 fields are investigated. It is shown that the density-of-states factor in a uniformly accelerated frame takes a complicated form, but the energy spectrum exhibits a Bose-Einstein or Fermi-Dirac distribution function. In particular, the Dirac sea shows thermal-like effects

Internalization and trafficking mechanisms of coxsackievirus B3 in HeLa cells

International Nuclear Information System (INIS)

Chung, Sun-Ku; Kim, Joo-Young; Kim, In-Beom; Park, Sang-Ick; Paek, Kyung-Hee; Nam, Jae-Hwan

2005-01-01

Coxsackievirus B3 (CVB3) is nonenveloped and has a single-stranded positive-sense RNA genome. CVB3 induces myocarditis and ultimately dilated cardiomyopathy. Although there are mounting evidences of an interaction between CVB3 particles and the cellular receptors, coxsackievirus and adenovirus receptor (CAR) and decay-accelerating factor (DAF), very little is known about the mechanisms of internalization and trafficking. In the present study, we used the CVB3 H3 strain, which is CAR-dependent but DAF-independent Woodruff variant and found that during entry, CVB3 particles were colocalized in clathrin, after interacting primarily with CAR, which was not recycled to the plasma membrane. We also found that CVB3 internalization was dependent on the function of dynamin, a large GTPase that has an essential role in endocytosis. Heat-shock cognate protein, Hsc70, which acts as a chaperone in the release of coat proteins from clathrin-coated vesicles (CCV), played a role in CVB3 trafficking processes. Moreover, endosomal acidification was crucial for CVB3 endocytosis. Finally, CVB3 was colocalized in early endosome autoantigen 1 (EEA1) molecules, which are involved in endosome-endosome tethering and fusion. In conclusion, these data together indicate that CVB3 uses clathrin-mediated endocytosis and is transcytosed to early endosomes

Inspection of piping wall loss with flow accelerated corrosion accelerated simulation test

International Nuclear Information System (INIS)

Ryu, Kyung Ha; Kim, Ji Hak; Hwang, Il Soon; Lee, Na Young; Kim, Ji Hyun

2009-01-01

Flow Accelerated Corrosion (FAC) has become a hot issue for aging of passive components. Ultrasonic Technique (UT) has been adopted to inspect the secondary piping of Nuclear Power Plants (NPPs). UT, however, uses point detection method, which results in numerous detecting points and thus takes time. We developed an Equipotential Switching Direct Current Potential Drop (ES-DCPD) method to monitor the thickness of piping that covers wide range of piping at once time. Since the ES-DCPD method covers area, not a point, it needs less monitoring time. This can be a good approach to broad carbon steel piping system such as secondary piping of NPPs. In this paper, FAC accelerated simulation test results is described. We realized accelerated FAC phenomenon by 2 times test: 23.7% thinning in 216.7 hours and 51% thinning in 795 hours. These were monitored by ES-DCPD and traditional UT. Some parameters of water chemistry are monitored and controlled to accelerate FAC process. As sensitive factors on FAC, temperature and pH was changed during the test. The wall loss monitored results reflected these changes of water chemistry successfully. Developed electrodes are also applied to simulation loop to monitor water chemistry. (author)

Does electromagnetic radiation accelerate galactic cosmic rays

Science.gov (United States)

Eichler, D.

1977-01-01

The 'reactor' theories of Tsytovich and collaborators (1973) of cosmic-ray acceleration by electromagnetic radiation are examined in the context of galactic cosmic rays. It is shown that any isotropic synchrotron or Compton reactors with reasonable astrophysical parameters can yield particles with a maximum relativistic factor of only about 10,000. If they are to produce particles with higher relativistic factors, the losses due to inverse Compton scattering of the electromagnetic radiation in them outweigh the acceleration, and this violates the assumptions of the theory. This is a critical restriction in the context of galactic cosmic rays, which have a power-law spectrum extending up to a relativistic factor of 1 million.

Genes that act downstream of sensory neurons to influence longevity, dauer formation, and pathogen responses in Caenorhabditis elegans.

Directory of Open Access Journals (Sweden)

Marta M Gaglia

Full Text Available The sensory systems of multicellular organisms are designed to provide information about the environment and thus elicit appropriate changes in physiology and behavior. In the nematode Caenorhabditis elegans, sensory neurons affect the decision to arrest during development in a diapause state, the dauer larva, and modulate the lifespan of the animals in adulthood. However, the mechanisms underlying these effects are incompletely understood. Using whole-genome microarray analysis, we identified transcripts whose levels are altered by mutations in the intraflagellar transport protein daf-10, which result in impaired development and function of many sensory neurons in C. elegans. In agreement with existing genetic data, the expression of genes regulated by the transcription factor DAF-16/FOXO was affected by daf-10 mutations. In addition, we found altered expression of transcriptional targets of the DAF-12/nuclear hormone receptor in the daf-10 mutants and showed that this pathway influences specifically the dauer formation phenotype of these animals. Unexpectedly, pathogen-responsive genes were repressed in daf-10 mutant animals, and these sensory mutants exhibited altered susceptibility to and behavioral avoidance of bacterial pathogens. Moreover, we found that a solute transporter gene mct-1/2, which was induced by daf-10 mutations, was necessary and sufficient for longevity. Thus, sensory input seems to influence an extensive transcriptional network that modulates basic biological processes in C. elegans. This situation is reminiscent of the complex regulation of physiology by the mammalian hypothalamus, which also receives innervations from sensory systems, most notably the visual and olfactory systems.

Are malnutrition and stress risk factors for accelerated cognitive decline? A prisoner of war study.

Science.gov (United States)

Sulway, M R; Broe, G A; Creasey, H; Dent, O F; Jorm, A F; Kos, S C; Tennant, C C

1996-03-01

We set out to test the hypothesis that severe malnutrition and stress experienced by prisoners of war (POWs) are associated with cognitive deficits later in life. We assessed 101 former Australian POWs of the Japanese and 108 veteran control subjects using a battery of neuropsychological tests, a depression scale, a clinical examination for dementia, and CT. We divided the POWs into high weight loss (>35%) and low weight loss groups (malnutrition is a risk factor for accelerated cognitive decline nor the theory that severe stress can lead to hippocampal neuronal loss and cognitive deficits. Cognitive deficits in earlier studies of former POWs may have been associated with concurrent depression.

Accelerator Physics Branch annual technical report, 1989

International Nuclear Information System (INIS)

Hulbert, J.A.

1990-08-01

The report describes, in a series of separate articles, the achievements of the Accelerator Physics Branch for the calendar year 1989. Work in basic problems of accelerator physics including ion sources, high-duty-factor rf quadrupoles, coupling effects in standing wave linacs and laser acceleration is outlined. A proposal for a synchrotron light source for Canada is described. Other articles cover the principal design features of the IMPELA industrial electron linac prototype, the cavities developed for the HERA complex at DESY, Hamburg, West Germany, and further machine projects that have been completed

Acceleration of Medpor implant fibrovascularization with local vascular endothelial growth-factor injections: An experimental study

Directory of Open Access Journals (Sweden)

Mert Demirel

2015-12-01

Full Text Available Objective: Medpor is a biocompatible, high-density porous polyethylene implant that is used for multiple indications in plastic surgery. The most frequent complications associated with the Medpor implant are infection and implant exposure. The primary cause of these complications is poor fibrovascularization of the Medpor implant and poor nourishment of the overlying skin. The present experimental study aimed to determine whether vascular endothelial growth factor (VEGF could accelerate and increase Medpor implant fibrovascularization in vivo, and thereby improve local nourishment and prevent complications. Materials and Methods: The Medpor implant was inserted under the dorsal skin area in 40 Sprague-Dawley rats. 20 rats receiving local VEGF injections comprised the study group. The control group received saline injections. Fibrovascularization of the Medpor implants was compared. Results: In the rats injected with VEGF, the Medpor implant fibrovascularized faster, and there were more newly formed blood vessels, as compared with those in the control group. Conclusion: These findings have led to our use of VEGF-like agents that the accelerate angiogenesis in the Medpor implant as a means to reduce the incidence of such complications as infection and implant exposure. [Arch Clin Exp Surg 2015; 4(4.000: 196-201

Diapause formation and downregulation of insulin-like signaling via DAF-16/FOXO delays axonal degeneration and neuronal loss.

Directory of Open Access Journals (Sweden)

Andrea Calixto

Full Text Available Axonal degeneration is a key event in the pathogenesis of neurodegenerative conditions. We show here that mec-4d triggered axonal degeneration of Caenorhabditis elegans neurons and mammalian axons share mechanistical similarities, as both are rescued by inhibition of calcium increase, mitochondrial dysfunction, and NMNAT overexpression. We then explore whether reactive oxygen species (ROS participate in axonal degeneration and neuronal demise. C. elegans dauers have enhanced anti-ROS systems, and dauer mec-4d worms are completely protected from axonal degeneration and neuronal loss. Mechanistically, downregulation of the Insulin/IGF-1-like signaling (IIS pathway protects neurons from degenerating in a DAF-16/FOXO-dependent manner and is related to superoxide dismutase and catalase-increased expression. Caloric restriction and systemic antioxidant treatment, which decrease oxidative damage, protect C. elegans axons from mec-4d-mediated degeneration and delay Wallerian degeneration in mice. In summary, we show that the IIS pathway is essential in maintaining neuronal homeostasis under pro-degenerative stimuli and identify ROS as a key intermediate of neuronal degeneration in vivo. Since axonal degeneration represents an early pathological event in neurodegeneration, our work identifies potential targets for therapeutic intervention in several conditions characterized by axonal loss and functional impairment.

Accelerating an Ordered-Subset Low-Dose X-Ray Cone Beam Computed Tomography Image Reconstruction with a Power Factor and Total Variation Minimization.

Science.gov (United States)

Huang, Hsuan-Ming; Hsiao, Ing-Tsung

2016-01-01

In recent years, there has been increased interest in low-dose X-ray cone beam computed tomography (CBCT) in many fields, including dentistry, guided radiotherapy and small animal imaging. Despite reducing the radiation dose, low-dose CBCT has not gained widespread acceptance in routine clinical practice. In addition to performing more evaluation studies, developing a fast and high-quality reconstruction algorithm is required. In this work, we propose an iterative reconstruction method that accelerates ordered-subsets (OS) reconstruction using a power factor. Furthermore, we combine it with the total-variation (TV) minimization method. Both simulation and phantom studies were conducted to evaluate the performance of the proposed method. Results show that the proposed method can accelerate conventional OS methods, greatly increase the convergence speed in early iterations. Moreover, applying the TV minimization to the power acceleration scheme can further improve the image quality while preserving the fast convergence rate.

Tractor accelerated test on test rig

Directory of Open Access Journals (Sweden)

M. Mattetti

2013-09-01

Full Text Available The experimental tests performed to validate a tractor prototype before its production, need a substantial financial and time commitment. The tests could be reduced using accelerated tests able to reproduce on the structural part of the tractor, the same damage produced on the tractor during real life in a reduced time. These tests were usually performed reproducing a particular harsh condition a defined number of times, as for example using a bumpy road on track to carry out the test in any weather condition. Using these procedures the loads applied on the tractor structure are different with respect to those obtained during the real use, with the risk to apply loads hard to find in reality. Recently it has been demonstrated how, using the methodologies designed for cars, it is possible to also expedite the structural tests for tractors. In particular, automotive proving grounds were recently successfully used with tractors to perform accelerated structural tests able to reproduce the real use of the machine with an acceleration factor higher than that obtained with the traditional methods. However, the acceleration factor obtained with a tractor on proving grounds is in any case reduced due to the reduced speed of the tractors with respect to cars. In this context, the goal of the paper is to show the development of a methodology to perform an accelerated structural test on a medium power tractor using a 4 post test rig. In particular, several proving ground testing conditions have been performed to measure the loads on the tractor. The loads obtained were then edited to remove the not damaging portion of signals, and finally the loads obtained were reproduced in a 4 post test rig. The methodology proposed could be a valid alternative to the use of a proving ground to reproduce accelerated structural tests on tractors.

Unprecedented quality factors at accelerating gradients up to 45 MVm ^-1 in niobium superconducting resonators via low temperature nitrogen infusion

Energy Technology Data Exchange (ETDEWEB)

Grassellino, A.; Romanenko, A.; Trenikhina, Y.; Checchin, M.; Martinello, M.; Melnychuk, O. S.; Chandrasekaran, S.; Sergatskov, D. A.; Posen, S.; Crawford, A. C.; Aderhold, S.; Bice, D.

2017-08-14

We report the finding of new surface treatments that permit to manipulate the niobium resonator nitrogen content in the first few nanometers in a controlled way, and the resonator fundamental Mattis-Bardeen surface resistance and residual resistance accordingly. In particular, we find surface infusion conditions that systematically a) increase the quality factor of these 1.3 GHz superconducting radio frequency (SRF) bulk niobium resonators, up to very high gradients; b) increase the achievable accelerating gradient of the cavity compared to its own baseline with state-of-the-art surface processing. Cavities subject to the new surface process have larger than two times the state of the art Q at 2K for accelerating fields > 35 MV/m. Moreover, very high accelerating gradients ~ 45 MV/m are repeatedly reached, which correspond to peak magnetic surface fields of 190 mT, among the highest measured for bulk niobium cavities. These findings open the opportunity to tailor the surface impurity content distribution to maximize performance in Q and gradients, and have therefore very important implications on future performance and cost of SRF based accelerators. They also help deepen the understanding of the physics of the RF niobium cavity surface.

Relativistic ion acceleration by ultraintense laser interactions

International Nuclear Information System (INIS)

Nakajima, K.; Koga, J.K.; Nakagawa, K.

2001-01-01

There has been a great interest in relativistic particle generation by ultraintense laser interactions with matter. We propose the use of relativistically self-focused laser pulses for the acceleration of ions. Two dimensional PIC simulations are performed, which show the formation of a large positive electrostatic field near the front of a relativistically self-focused laser pulse. Several factors contribute to the acceleration including self-focusing distance, pulse depletion, and plasma density. Ultraintense laser-plasma interactions are capable of generating enormous electrostatic fields of ∼3 TV/m for acceleration of protons with relativistic energies exceeding 1 GeV

Downregulation of the Hsp90 system causes defects in muscle cells of Caenorhabditis elegans.

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Andreas M Gaiser

Full Text Available The ATP-dependent molecular chaperone Hsp90 is required for the activation of a variety of client proteins involved in various cellular processes. Despite the abundance of known client proteins, functions of Hsp90 in the organismal context are not fully explored. In Caenorhabditis elegans, Hsp90 (DAF-21 has been implicated in the regulation of the stress-resistant dauer state, in chemosensing and in gonad formation. In a C. elegans strain carrying a DAF-21 mutation with a lower ATP turnover, we observed motility defects. Similarly, a reduction of DAF-21 levels in wild type nematodes leads to reduced motility and induction of the muscular stress response. Furthermore, aggregates of the myosin MYO-3 are visible in muscle cells, if DAF-21 is depleted, implying a role of Hsp90 in the maintenance of muscle cell functionality. Similar defects can also be observed upon knockdown of the Hsp90-cochaperone UNC-45. In life nematodes YFP-DAF-21 localizes to the I-band and the M-line of the muscular ultrastructure, but the protein is not stably attached there. The Hsp90-cofactor UNC-45-CFP contrarily can be found in all bands of the nematode muscle ultrastructure and stably associates with the UNC-54 containing A-band. Thus, despite the physical interaction between DAF-21 and UNC-45, apparently the two proteins are not always localized to the same muscular structures. While UNC-45 can stably bind to myofilaments in the muscular ultrastructure, Hsp90 (DAF-21 appears to participate in the maintenance of muscle structures as a transiently associated diffusible factor.

Insulin Signaling in the Aging of Healthy and Proteotoxically Stressed Mechanosensory Neurons

Directory of Open Access Journals (Sweden)

Courtney eScerbak

2014-07-01

Full Text Available Insulin signaling is central to cellular metabolism and organismal aging. However, the role of insulin signaling in natural and proteotoxically stressed aging neurons has yet to be fully described. We studied aging of Caenorbaditis elegans mechanosensory neurons expressing a neurotoxic expanded polyglutamine transgene (polyQ128, or lacking this proteotoxicity stressor (polyQ0, under conditions in which the insulin signaling pathway was disrupted by RNA interference (RNAi. We describe specific changes in lifespan, mechanosensory neuronal morphologies, and mechansensory function following RNAi treatment targeting the insulin signaling pathway. Overall, we confirmed that transcription factor DAF-16 is neuroprotective in the proteotoxically stressed model, though not strikingly in the naturally aging model. Decreased insulin signaling through daf-2 RNAi improved mechanosensory function in both models and decreased protein aggregation load in polyQ128, yet showed opposing effects on accumulation of neuronal aberrations in both strains. Decreased daf-2 signaling slightly enhanced mechanosensation while greatly enhancing branching of the mechanosensory neuron axons and dendrites in polyQ0 animals, suggesting that branching is an adaptive response in natural aging. These effects in polyQ0 did not appear to involve DAF-16, suggesting the existence of a non-canonical DAF-2 pathway for the modulation of morphological adaptation. However, in polyQ128 animals, decreased daf-2 signaling significantly enhanced mechanosensation while decreasing neuronal aberrations. Unlike other interventions that reduce the strength of insulin signaling, daf-2 RNAi dramatically redistributed large polyQ128 aggregates to the cell body, away from neuronal processes. Our results suggest that insulin signaling strength can differentially affect specific neurons aging naturally or under proteotoxic stress.

Metabolic syndrome but not obesity measures are risk factors for accelerated age-related glomerular filtration rate decline in the general population.

Science.gov (United States)

Stefansson, Vidar T N; Schei, Jørgen; Solbu, Marit D; Jenssen, Trond G; Melsom, Toralf; Eriksen, Bjørn O

2018-05-01

Rapid age-related glomerular filtration rate (GFR) decline increases the risk of end-stage renal disease, and a low GFR increases the risk of mortality and cardiovascular disease. High body mass index and the metabolic syndrome are well-known risk factors for patients with advanced chronic kidney disease, but their role in accelerating age-related GFR decline independent of cardiovascular disease, hypertension and diabetes is not adequately understood. We studied body mass index, waist circumference, waist-hip ratio and metabolic syndrome as risk factors for accelerated GFR decline in 1261 middle-aged people representative of the general population without diabetes, cardiovascular disease or kidney disease. GFR was measured as iohexol clearance at baseline and repeated after a median of 5.6 years. Metabolic syndrome was defined as fulfilling three out of five criteria, based on waist circumference, blood pressure, glucose, high-density lipoprotein cholesterol and triglycerides. The mean GFR decline rate was 0.95 ml/min/year. Neither the body mass index, waist circumference nor waist-hip ratio predicted statistically significant changes in age-related GFR decline, but individuals with baseline metabolic syndrome had a significant mean of 0.30 ml/min/year faster decline than individuals without metabolic syndrome in a multivariable adjusted linear regression model. This association was mainly driven by the triglyceride criterion of metabolic syndrome, which was associated with a significant 0.36 ml/min/year faster decline when analyzed separately. Results differed significantly when GFR was estimated using creatinine and/or cystatin C. Thus, metabolic syndrome, but not the body mass index, waist circumference or waist-hip ratio, is an independent risk factor for accelerated age-related GFR decline in the general population. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Statistical analysis of data from accelerated ageing tests of PES UF membranes

NARCIS (Netherlands)

Zondervan, Edwin; Zwijnenburg, Arie; Roffel, Brian

2007-01-01

In this research, membrane life-time was evaluated by means of accelerated ageing experiments. A pressure pulse unit was used to perform the ageing experiments in an accelerated way. An experimental design has been set up and four ageing factors were varied at two levels. The four ageing factors

Determination of small field synthetic single-crystal diamond detector correction factors for CyberKnife, Leksell Gamma Knife Perfexion and linear accelerator.

Science.gov (United States)

Veselsky, T; Novotny, J; Pastykova, V; Koniarova, I

2017-12-01

The aim of this study was to determine small field correction factors for a synthetic single-crystal diamond detector (PTW microDiamond) for routine use in clinical dosimetric measurements. Correction factors following small field Alfonso formalism were calculated by comparison of PTW microDiamond measured ratio M Qclin fclin /M Qmsr fmsr with Monte Carlo (MC) based field output factors Ω Qclin,Qmsr fclin,fmsr determined using Dosimetry Diode E or with MC simulation itself. Diode measurements were used for the CyberKnife and Varian Clinac 2100C/D linear accelerator. PTW microDiamond correction factors for Leksell Gamma Knife (LGK) were derived using MC simulated reference values from the manufacturer. PTW microDiamond correction factors for CyberKnife field sizes 25-5 mm were mostly smaller than 1% (except for 2.9% for 5 mm Iris field and 1.4% for 7.5 mm fixed cone field). The correction of 0.1% and 2.0% for 8 mm and 4 mm collimators, respectively, needed to be applied to PTW microDiamond measurements for LGK Perfexion. Finally, PTW microDiamond M Qclin fclin /M Qmsr fmsr for the linear accelerator varied from MC corrected Dosimetry Diode data by less than 0.5% (except for 1 × 1 cm 2 field size with 1.3% deviation). Regarding low resulting correction factor values, the PTW microDiamond detector may be considered an almost ideal tool for relative small field dosimetry in a large variety of stereotactic and radiosurgery treatment devices. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Glycosyl-phosphatidylinositol (GPI)-anchored membrane association of the porcine reproductive and respiratory syndrome virus GP4 glycoprotein and its co-localization with CD163 in lipid rafts

Energy Technology Data Exchange (ETDEWEB)

Du, Yijun [Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Ave, Urbana, IL 61802 (United States); Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan (China); Pattnaik, Asit K. [School of Veterinary Medicine and Biomedical Sciences and the Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE 68583-0900 (United States); Song, Cheng [Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Ave, Urbana, IL 61802 (United States); Yoo, Dongwan, E-mail: dyoo@illinois.edu [Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Ave, Urbana, IL 61802 (United States); Li, Gang, E-mail: dyoo@illinois.edu [Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Ave, Urbana, IL 61802 (United States); Institute of Animal Science and Veterinary Medicine, Chinese Academy of Agricultural Sciences, Beijing (China)

2012-03-01

The porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 4 (GP4) resembles a typical type I membrane protein in its structure but lacks a hydrophilic tail at the C-terminus, suggesting that GP4 may be a lipid-anchored membrane protein. Using the human decay-accelerating factor (DAF; CD55), a known glycosyl-phosphatidylinositol (GPI) lipid-anchored protein, chimeric constructs were made to substitute the GPI-anchor domain of DAF with the putative lipid-anchor domain of GP4, and their membrane association and lipase cleavage were determined in cells. The DAF-GP4 fusion protein was transported to the plasma membrane and was cleaved by phosphatidylinositol-specific phospholipase C (PI-PLC), indicating that the C-terminal domain of GP4 functions as a GPI anchor. Mutational studies for residues adjacent to the GPI modification site and characterization of respective mutant viruses generated from infectious cDNA clones show that the ability of GP4 for membrane association corresponded to virus viability and growth characteristics. The residues T158 ({omega} - 2, where {omega} is the GPI moiety at E160), P159 ({omega} - 1), and M162 ({omega} + 2) of GP4 were determined to be important for virus replication, with M162 being of particular importance for virus infectivity. The complete removal of the peptide-anchor domain in GP4 resulted in a complete loss of virus infectivity. The depletion of cholesterol from the plasma membrane of cells reduced the virus production, suggesting a role of lipid rafts in PRRSV infection. Remarkably, GP4 was found to co-localize with CD163 in the lipid rafts on the plasma membrane. Since CD163 has been reported as a cellular receptor for PRRSV and GP4 has been shown to interact with this receptor, our data implicates an important role of lipid rafts during entry of the virus.

Glycosyl-phosphatidylinositol (GPI)-anchored membrane association of the porcine reproductive and respiratory syndrome virus GP4 glycoprotein and its co-localization with CD163 in lipid rafts

International Nuclear Information System (INIS)

Du, Yijun; Pattnaik, Asit K.; Song, Cheng; Yoo, Dongwan; Li, Gang

2012-01-01

The porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 4 (GP4) resembles a typical type I membrane protein in its structure but lacks a hydrophilic tail at the C-terminus, suggesting that GP4 may be a lipid-anchored membrane protein. Using the human decay-accelerating factor (DAF; CD55), a known glycosyl-phosphatidylinositol (GPI) lipid-anchored protein, chimeric constructs were made to substitute the GPI-anchor domain of DAF with the putative lipid-anchor domain of GP4, and their membrane association and lipase cleavage were determined in cells. The DAF-GP4 fusion protein was transported to the plasma membrane and was cleaved by phosphatidylinositol-specific phospholipase C (PI-PLC), indicating that the C-terminal domain of GP4 functions as a GPI anchor. Mutational studies for residues adjacent to the GPI modification site and characterization of respective mutant viruses generated from infectious cDNA clones show that the ability of GP4 for membrane association corresponded to virus viability and growth characteristics. The residues T158 (ω − 2, where ω is the GPI moiety at E160), P159 (ω − 1), and M162 (ω + 2) of GP4 were determined to be important for virus replication, with M162 being of particular importance for virus infectivity. The complete removal of the peptide–anchor domain in GP4 resulted in a complete loss of virus infectivity. The depletion of cholesterol from the plasma membrane of cells reduced the virus production, suggesting a role of lipid rafts in PRRSV infection. Remarkably, GP4 was found to co-localize with CD163 in the lipid rafts on the plasma membrane. Since CD163 has been reported as a cellular receptor for PRRSV and GP4 has been shown to interact with this receptor, our data implicates an important role of lipid rafts during entry of the virus.

Accelerating cosmologies from exponential potentials

International Nuclear Information System (INIS)

Neupane, Ishwaree P.

2003-11-01

It is learnt that exponential potentials of the form V ∼ exp(-2cφ/M p ) arising from the hyperbolic or flux compactification of higher-dimensional theories are of interest for getting short periods of accelerated cosmological expansions. Using a similar potential but derived for the combined case of hyperbolic-flux compactification, we study a four-dimensional flat (or open) FRW cosmologies and give analytic (and numerical) solutions with exponential behavior of scale factors. We show that, for the M-theory motivated potentials, the cosmic acceleration of the universe can be eternal if the spatial curvature of the 4d spacetime is negative, while the acceleration is only transient for a spatially flat universe. We also briefly discuss about the mass of massive Kaluza-Klein modes and the dynamical stabilization of the compact hyperbolic extra dimensions. (author)

High current electron beam acceleration in dielectric-filled RF cavities

International Nuclear Information System (INIS)

Faehl, R.J.; Keinigs, R.K.

1996-01-01

The acceleration of charged particles in radio frequency (RF) cavities is a widely used mode in high energy accelerators. Advantages include very high accelerating gradients and very stable phase control. A traditional limitation for such acceleration has been their use for intense, high current beam generation. This constraint arises from the inability to store a large amount of electromagnetic energy in the cavity and from loading effects of the beam on the cavity. The authors have studied a simple modification to transcend these limitations. Following Humphries and Huang, they have conducted analytic and numerical investigations of RF accelerator cavities in which a high dielectric constant material, such as water, replaces most of the cavity volume. This raises the stored energy in a cavity of given dimensions by a factor var-epsilon/var-epsilon 0 . For a water fill, var-epsilon/var-epsilon 0 ∼ 80, depending on the frequency. This introduction of high dielectric constant material into the cavity reduces the resonant frequencies by a factor of (var-epsilon/var-epsilon 0 ) 1/2 . This reduced operating frequency mans that existing high efficiency power supplies, at lower frequencies, can be used for an accelerator

Research project on accelerator-driven subcritical system using FFAG accelerator and Kyoto University critical assembly

International Nuclear Information System (INIS)

Mishima, Kaichiro; Unesaki, Hironobu; Misawa, Tsuyoshi; Tanigaki, Minoru; Mori, Yoshiharu; Shiroya, Seiji; Inoue, Makoto; Ishi, Y.; Fukumoto, Shintaro

2005-01-01

The KART (Kumatori Accelerator-driven Reactor Test facility) project started in Research Reactor Institute, Kyoto University in fiscal year 2002 with the grant by the Japanese Ministry of Education, Culture, Sports, Science and Technology. The purpose of this research project is to demonstrate the basis feasibility of accelerator driven system (ADS), studying the effect of incident neutron energy on the effective multiplication factor in a subcritical nuclear fuel system. For this purpose, a variable-energy FFAG (Fixed Field Alternating Gradient) accelerator complex is being constructed to be coupled with the Kyoto University Critical Assembly (KUCA). The FFAG proton accelerator complex consists of ion-beta, booster and main rings. This system aims to attain 1 μA proton beam with energy range from 20 to 150 MeV with a repetition rate of 120 Hz. The first beam from the FFAG complex is expected to be available by the end of FY 2005, and the experiment on ADS with KUCA and the FFAG complex (FFAG-KUCA experiment) will start in FY 2006. Before the FFAG-KUCA experiment starts, preliminary experiments with 14 MeV neutrons are currently being performed using a Cockcroft-Walton type accelerator coupled with the KUCA. Experimental data are analyzed using continuous energy Monte-Carlo codes MVP, MCNP and MNCP-X. (author)

Molecular characterisation of Colombian yam germplasm by "DNA amplification fingerprinting (DAF" in radioactivo conditions

Directory of Open Access Journals (Sweden)

Silvia L. Bustamante

2003-07-01

Full Text Available Samples from the Universidad de Córdoba's yam collection (Dioscorea spp. and others originating from IITA (International Institute of Tropical Agriculture, Ibadan, Nigeria were molecularly characterised to complement existing information about them. The yam (Diosocorea spp. represents a basic crop for small-scale farmers on the Colombian Atlantic Coast who sow around 20,000 hectares per year. Even though they are dioecious species, only one sex is represented in Colombia; it must also be stated that climatic conditions are not propitious for its flowering. This situation has caused difficulty for work in yam breeding. The yam species and varieties used in the Colombian ABP (Agricultural Biotechnology Programme have been molecularly characterised by AFLPs in a previous publication describing a preliminary study emerging from the need to broaden the characterisation of those accessions kept at the Universidad de Córdoba. Comparisons have also been done with some African accessions donated by IITA. In this article, samples were molecularly characterised by another fingerprinting technique, the DAF technique (DNA Amplification Fingerprinting based on PCR, using random oligonucleotides for generating characteristic band patterns from each individual. The results showed 0.0413 population diversity with 0.9587 average similarity, indicating that the yam collection studied had very little genetic diversity and, probably, this could be why the crop is vulnerable to plagues and diseases, as happened at the end of the 1980s when anthracnose practically devastated the crop on the Colombian Atlantic coast. Similarity was also found between those Colombian and African samples analysed, agreeing with low diversity and less distance between common ancestors. The molecular results suggest the need for using other molecular techniques having a greater power of discrimination and also the need to broaden the genetic diversity in yam crops for providing greater

A hybrid dielectric and iris loaded periodic accelerating structure

International Nuclear Information System (INIS)

Zou, P.; Xiao, L.; Sun, X.; Gai, W.

2001-01-01

One disadvantage of conventional iris-loaded accelerating structures is the high ratio of the peak surface electric field to the peak axial electric field useful for accelerating a beam. Typically this ratio E s /E a ≥ 2. The high surface electric field relative to the accelerating gradient may prove to be a limitation for realizing technologies for very high gradient accelerators. In this paper, we present a scheme that uses a hybrid dielectric and iris loaded periodic structure to reduce E s /E a to near unity, while the shunt impedance per unit length r and the quality factor Q compare favorably with conventional metallic structures. The analysis based on MAFIA simulations of such structures shows that we can lower the peak surface electric field close to the accelerating gradient while maintaining high acceleration efficiency as measured by r/Q. Numerical examples of X-band hybrid accelerating structures are given

Plasma accelerators

International Nuclear Information System (INIS)

Bingham, R.; Angelis, U. de; Johnston, T.W.

1991-01-01

Recently attention has focused on charged particle acceleration in a plasma by a fast, large amplitude, longitudinal electron plasma wave. The plasma beat wave and plasma wakefield accelerators are two efficient ways of producing ultra-high accelerating gradients. Starting with the plasma beat wave accelerator (PBWA) and laser wakefield accelerator (LWFA) schemes and the plasma wakefield accelerator (PWFA) steady progress has been made in theory, simulations and experiments. Computations are presented for the study of LWFA. (author)

Microdroplets Accelerate Ring Opening of Epoxides

Science.gov (United States)

Lai, Yin-Hung; Sathyamoorthi, Shyam; Bain, Ryan M.; Zare, Richard N.

2018-05-01

The nucleophilic opening of an epoxide is a classic organic reaction that has widespread utility in both academic and industrial applications. We have studied the reaction of limonene oxide with morpholine to form 1-methyl-2-morpholino-4-(prop-1-en-2-yl) cyclohexan-1-ol in bulk solution and in electrosprayed microdroplets with a 1:1 v/ v water/methanol solvent system. We find that even after 90 min at room temperature, there is no product detected by nuclear magnetic resonance spectroscopy in bulk solution whereas in room-temperature microdroplets (2-3 μm in diameter), the yield is already 0.5% in a flight time of 1 ms as observed by mass spectrometry. This constitutes a rate acceleration of 105 in the microdroplet environment, if we assume that as much as 5% of product is formed in bulk after 90 min of reaction time. We examine how the reaction rate depends on droplet size, solvent composition, sheath gas pressure, and applied voltage. These factors profoundly influence the extent of reaction. This dramatic acceleration is not limited to just one system. We have also found that the nucleophilic opening of cis-stilbene oxide by morpholine is similarly accelerated. Such large acceleration factors in reaction rates suggest the use of microdroplets for ring opening of epoxides in other systems, which may have practical significance if such a procedure could be scaled. [Figure not available: see fulltext.

Microdroplets Accelerate Ring Opening of Epoxides

Science.gov (United States)

Lai, Yin-Hung; Sathyamoorthi, Shyam; Bain, Ryan M.; Zare, Richard N.

2018-03-01

The nucleophilic opening of an epoxide is a classic organic reaction that has widespread utility in both academic and industrial applications. We have studied the reaction of limonene oxide with morpholine to form 1-methyl-2-morpholino-4-(prop-1-en-2-yl) cyclohexan-1-ol in bulk solution and in electrosprayed microdroplets with a 1:1 v/v water/methanol solvent system. We find that even after 90 min at room temperature, there is no product detected by nuclear magnetic resonance spectroscopy in bulk solution whereas in room-temperature microdroplets (2-3 μm in diameter), the yield is already 0.5% in a flight time of 1 ms as observed by mass spectrometry. This constitutes a rate acceleration of 105 in the microdroplet environment, if we assume that as much as 5% of product is formed in bulk after 90 min of reaction time. We examine how the reaction rate depends on droplet size, solvent composition, sheath gas pressure, and applied voltage. These factors profoundly influence the extent of reaction. This dramatic acceleration is not limited to just one system. We have also found that the nucleophilic opening of cis-stilbene oxide by morpholine is similarly accelerated. Such large acceleration factors in reaction rates suggest the use of microdroplets for ring opening of epoxides in other systems, which may have practical significance if such a procedure could be scaled. [Figure not available: see fulltext.

Acceleration factor for propagation of a stationary wave in its wave medium: movement of energy in the 3-D space

International Nuclear Information System (INIS)

Nagao, Shigeto

2013-01-01

According to the formerly reported 4-D spherical model of the time and universe, any energy in the 3-dimensional space is a vibration of the intrinsic space energy. There is a special frame stationary to the space energy and the principle of relativity is no longer valid. Accordingly, abandonment of the Special Relativity and then introduction of a factor of acceleration for energy in the 3-D space are proposed.

Daintain/AIF-1 (Allograft Inflammatory Factor-1) accelerates type 1 diabetes in NOD mice

Energy Technology Data Exchange (ETDEWEB)

Zhao, Yan-Ying, E-mail: biozyy@163.com [College of Life Science and Technology, Southwest University for Nationalities, Chengdu 610041 (China); Huang, Xin-Yuan [College of Life Science and Technology, Hubei Engineering University, Xiaogan 432000 (China); Chen, Zheng-Wang [Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074 (China)

2012-10-26

Highlights: Black-Right-Pointing-Pointer Daintain/AIF-1 is over-expressed in the blood of NOD mice suffering from insulitis. Black-Right-Pointing-Pointer Daintain/AIF-1 stimulates white blood cell proliferation in NOD mice. Black-Right-Pointing-Pointer Daintain/AIF-1 increases blood glucose levels and triggers type 1 diabetes. Black-Right-Pointing-Pointer Daintain/AIF-1 accelerates insulitis, while its antibody prevents insulitis. Black-Right-Pointing-Pointer Daintain/AIF-1 enhances the levels of nitric oxide in the pancreases of NOD mice. -- Abstract: A large body of experimental evidence suggests that cytokines trigger pancreatic {beta}-cell death in type 1 diabetes mellitus. Daintain/AIF-1 (Allograft Inflammatory Factor-1), a specific marker for activated macrophages, is accumulated in the pancreatic islets of pre-diabetic BB rats. In the present study, we demonstrate that daintain/AIF-1 is released into blood and the levels of daintain/AIF-1 in the blood of type 1 diabetes-prone non-obese diabetic (NOD) mice suffering from insulitis are significantly higher than that in healthy NOD mice. When injected intravenously into NOD mice, daintain/AIF-1 stimulates white blood cell proliferation, increases the concentrations of blood glucose, impairs insulin expression, up-regulates nitric oxide (NO) production in pancreases and accelerates diabetes in NOD mice, while the antibody against daintain/AIF-1 delays or prevents insulitis in NOD mice. These results imply daintain/AIF-1 triggers type 1 diabetes probably via arousing immune cells activation and induction of NO production in pancreas of NOD mice.

Commissioning the GTA accelerator

International Nuclear Information System (INIS)

Sander, O.R.; Atkins, W.H.; Bolme, G.O.; Bowling, S.; Brown, S.; Cole, R.; Gilpatrick, J.D.; Garnett, R.; Guy, F.W.; Ingalls, W.B.; Johnson, K.F.; Kerstiens, D.; Little, C.; Lohsen, R.A.; Lloyd, S.; Lysenko, W.P.; Mottershead, C.T.; Neuschaefer, G.; Power, J.; Rusthoi, D.P.; Sandoval, D.P. Stevens, R.R. Jr.; Vaughn, G.; Wadlinger, E.A.; Yuan, V.; Connolly, R.; Weiss, R.; Saadatmand, K.

1992-01-01

The Ground Test Accelerator (GTA) is supported by the Strategic Defense command as part of their Neutral Particle Beam (NPB) program. Neutral particles have the advantage that in space they are unaffected by the earth's magnetic field and travel in straight lines unless they enter the earth's atmosphere and become charged by stripping. Heavy particles are difficult to stop and can probe the interior of space vehicles; hence, NPB can function as a discriminator between warheads and decoys. We are using GTA to resolve the physics and engineering issues related to accelerating, focusing, and steering a high-brightness, high-current H - beam and then neutralizing it. Our immediate goal is to produce a 24-MeV, 50mA device with a 2% duty factor

Effect of Water Chemistry Factors on Flow Accelerated Corrosion : pH, DO, Hydrazine

International Nuclear Information System (INIS)

Lee, Eun Hee; Kim, Kyung Mo; Kim, Hong Pyo

2013-01-01

Flow accelerated corrosion(FAC) of the carbon steel piping in pressurized water reactors(PWRs) has been major issue in nuclear industry. Severe accident at Surry Unit 2 in 1986 initiated the worldwide interest in this area. Major parameters influencing FAC are material composition, microstructure, water chemistry, and hydrodynamics. Qualitative behaviors of FAC have been well understood but quantitative data about FAC have not been published for proprietary reason. In order to minimize the FAC in PWRs, the optimal method is to control water chemistry factors. Chemistry factors influencing FAC such as pH, corrosion potential, and hydrazine contents were reviewed in this paper. FAC rate decreased with pH up to 10 because magnetite solubility decreased with pH. Corrosion potential is generally controlled dissolved oxygen (DO) and hydrazine in secondary water. DO increased corrosion potential. FAC rate decreased with DO by stabilizing magnetite at low DO concentration or by formation of hematite at high DO concentration. Even though hydrazine is generally used to remove DO, hydrazine itself thermally decomposed to ammonia, nitrogen, and hydrogen raising pH. Hydrazine could react with iron and increased FAC rate. Effect of hydrazine on FAC is rather complex and should be careful in FAC analysis. FAC could be managed by adequate combination of pH, corrosion potential, and hydrazine

Focus measurement of electron linear accelerator

International Nuclear Information System (INIS)

Su Zhijun; Xin Jian; Jia Qinglong

2007-01-01

Many personal factors would influence the result of the focus measurement of linear accelerator using the conventional sandwich method. This paper presents a modified method which applies a film scanning meter to scan the X-ray image film got by sandwich method for obtaining a greyscale distribution, then the full width at half maximum value of greyscale distribution represents the focus size. The method can eliminates disadvantage influence from accelerator radiant field asymmetry by quadratic polynomial fitting and measures peak width at half height instead of stripe statistic. (authors)

Aloe vera oral administration accelerates acute radiation-delayed wound healing by stimulating transforming growth factor-β and fibroblast growth factor production.

Science.gov (United States)

Atiba, Ayman; Nishimura, Mayumi; Kakinuma, Shizuko; Hiraoka, Takeshi; Goryo, Masanobu; Shimada, Yoshiya; Ueno, Hiroshi; Uzuka, Yuji

2011-06-01

Delayed wound healing is a significant clinical problem in patients who have had previous irradiation. This study investigated the effectiveness of Aloe vera (Av) on acute radiation-delayed wound healing. The effect of Av was studied in radiation-exposed rats compared with radiation-only and control rats. Skin wounds were excised on the back of rats after 3 days of local radiation. Wound size was measured on days 0, 3, 6, 9, and 12 after wounding. Wound tissues were examined histologically and the expressions of transforming growth factor β-1 (TGF-β-1) and basic fibroblast growth factor (bFGF) were examined by immunohistochemistry and reverse-transcription polymerase chain reaction. Wound contraction was accelerated significantly by Av on days 6 and 12 after wounding. Furthermore, the inflammatory cell infiltration, fibroblast proliferation, collagen deposition, angiogenesis, and the expression levels of TGF-β-1 and bFGF were significantly higher in the radiation plus Av group compared with the radiation-only group. These data showed the potential application of Av to improve the acute radiation-delayed wound healing by increasing TGF-β-1 and bFGF production. Copyright © 2011 Elsevier Inc. All rights reserved.

First muon acceleration using a radio-frequency accelerator

Directory of Open Access Journals (Sweden)

S. Bae

2018-05-01

Full Text Available Muons have been accelerated by using a radio-frequency accelerator for the first time. Negative muonium atoms (Mu^{-}, which are bound states of positive muons (μ^{+} and two electrons, are generated from μ^{+}’s through the electron capture process in an aluminum degrader. The generated Mu^{-}’s are initially electrostatically accelerated and injected into a radio-frequency quadrupole linac (RFQ. In the RFQ, the Mu^{-}’s are accelerated to 89 keV. The accelerated Mu^{-}’s are identified by momentum measurement and time of flight. This compact muon linac opens the door to various muon accelerator applications including particle physics measurements and the construction of a transmission muon microscope.

Acceleration Modes and Transitions in Pulsed Plasma Accelerators

Science.gov (United States)

Polzin, Kurt A.; Greve, Christine M.

2018-01-01

Pulsed plasma accelerators typically operate by storing energy in a capacitor bank and then discharging this energy through a gas, ionizing and accelerating it through the Lorentz body force. Two plasma accelerator types employing this general scheme have typically been studied: the gas-fed pulsed plasma thruster and the quasi-steady magnetoplasmadynamic (MPD) accelerator. The gas-fed pulsed plasma accelerator is generally represented as a completely transient device discharging in approximately 1-10 microseconds. When the capacitor bank is discharged through the gas, a current sheet forms at the breech of the thruster and propagates forward under a j (current density) by B (magnetic field) body force, entraining propellant it encounters. This process is sometimes referred to as detonation-mode acceleration because the current sheet representation approximates that of a strong shock propagating through the gas. Acceleration of the initial current sheet ceases when either the current sheet reaches the end of the device and is ejected or when the current in the circuit reverses, striking a new current sheet at the breech and depriving the initial sheet of additional acceleration. In the quasi-steady MPD accelerator, the pulse is lengthened to approximately 1 millisecond or longer and maintained at an approximately constant level during discharge. The time over which the transient phenomena experienced during startup typically occur is short relative to the overall discharge time, which is now long enough for the plasma to assume a relatively steady-state configuration. The ionized gas flows through a stationary current channel in a manner that is sometimes referred to as the deflagration-mode of operation. The plasma experiences electromagnetic acceleration as it flows through the current channel towards the exit of the device. A device that had a short pulse length but appeared to operate in a plasma acceleration regime different from the gas-fed pulsed plasma

A role for autophagy in the extension of lifespan by dietary restriction in C. elegans.

Directory of Open Access Journals (Sweden)

Malene Hansen

2008-02-01

Full Text Available In many organisms, dietary restriction appears to extend lifespan, at least in part, by down-regulating the nutrient-sensor TOR (Target Of Rapamycin. TOR inhibition elicits autophagy, the large-scale recycling of cytoplasmic macromolecules and organelles. In this study, we asked whether autophagy might contribute to the lifespan extension induced by dietary restriction in C. elegans. We find that dietary restriction and TOR inhibition produce an autophagic phenotype and that inhibiting genes required for autophagy prevents dietary restriction and TOR inhibition from extending lifespan. The longevity response to dietary restriction in C. elegans requires the PHA-4 transcription factor. We find that the autophagic response to dietary restriction also requires PHA-4 activity, indicating that autophagy is a transcriptionally regulated response to food limitation. In spite of the rejuvenating effect that autophagy is predicted to have on cells, our findings suggest that autophagy is not sufficient to extend lifespan. Long-lived daf-2 insulin/IGF-1 receptor mutants require both autophagy and the transcription factor DAF-16/FOXO for their longevity, but we find that autophagy takes place in the absence of DAF-16. Perhaps autophagy is not sufficient for lifespan extension because although it provides raw material for new macromolecular synthesis, DAF-16/FOXO must program the cells to recycle this raw material into cell-protective longevity proteins.

Earthquake acceleration amplification based on single microtremor test

Science.gov (United States)

Jaya Syahbana, Arifan; Kurniawan, Rahmat; Soebowo, Eko

2018-02-01

Understanding soil dynamics is needed to understand soil behaviour, including the parameters of earthquake acceleration amplification. Many researchers now conduct single microtremor tests to obtain amplification of velocity and natural periods of soil at test sites. However, these amplification parameters are rarely used, so a method is needed to convert the velocity amplification to acceleration amplification. This paper will discuss the proposed process of changing the value of amplification. The proposed method is to integrate the time histories of the synthetic earthquake acceleration of the soil surface under the deaggregation at that location so the time histories of the velocity earthquake will be obtained. Next is to conduct a “fitting curve” between amplification by a single microtremor test with amplification of the synthetic earthquake velocity time histories. After obtaining the fitting curve time histories of velocity, differentiation will be conducted to obtain fitting curve acceleration time histories. The final step after obtaining the fitting curve is to compare the acceleration of the “fitting curve” against the histories time of the acceleration of synthetic earthquake at bedrocks to obtain single microtremor acceleration amplification factor.

Highly efficient accelerator of dense matter using laser-induced cavity pressure acceleration

Czech Academy of Sciences Publication Activity Database

Badziak, J.; Jabloňski, S.; Pisarczyk, T.; Rączka, P.; Krouský, Eduard; Liska, R.; Kucharik, M.; Chodukowski, T.; Kalinowska, Z.; Parys, P.; Rosiński, M.; Borodziuk, S.; Ullschmied, Jiří

2012-01-01

Roč. 19, č. 5 (2012), s. 1-8 ISSN 1070-664X R&D Projects: GA MŠk(CZ) LC528 Institutional research plan: CEZ:AV0Z10100523; CEZ:AV0Z20430508 Keywords : plasma accelerators * plasma density * plasma inertial confinement * plasma light propagation * plasma pressure * plasma transport processes Subject RIV: BL - Plasma and Gas Discharge Physics Impact factor: 2.376, year: 2012

Evidence for Parallel Processing of Sensory Information Controlling Dauer Formation in Caenorhabditis Elegans

OpenAIRE

Thomas, J. H.; Birnby, D. A.; Vowels, J. J.

1993-01-01

Dauer formation in Caenorhabditis elegans is induced by chemosensation of high levels of a constitutively secreted pheromone. Seven genes defined by mutations that confer a dauer-formation constitutive phenotype (Daf-c) can be congruently divided into two groups by any of three criteria. Group 1 genes (daf-11 and daf-21) are (1) strongly synergistic with group 2 genes for their Daf-c phenotype, (2) incompletely suppressed by dauer-formation defective (Daf-d) mutations in the genes daf-3 and d...

Accelerator Technology: Geodesy and Alignment for Particle Accelerators

CERN Document Server

Missiaen, D

2013-01-01

This document is part of Subvolume C 'Accelerators and Colliders' of Volume 21 'Elementary Particles' of Landolt-Börnstein - Group I 'Elementary Particles, Nuclei and Atoms'. It contains the the Section '8.9 Geodesy and Alignment for Particle Accelerators' of the Chapter '8 Accelerator Technology' with the content: 8.9 Geodesy and Alignment for Particle Accelerators 8.9.1 Introduction 8.9.2 Reference and Co-ordinate Systems 8.9.3 Definition of the Beam Line on the Accelerator Site 8.9.4 Geodetic Network 8.9.5 Tunnel Preliminary Works 8.9.6 The Alignment References 8.9.7 Alignment of Accelerator Components 8.9.8 Permanent Monitoring and Remote Alignment of Low Beta Quadrupoles 8.9.9 Alignment of Detector Components

Neutron electromagnetic form factors

International Nuclear Information System (INIS)

Finn, J.M.; Madey, R.; Eden, T.; Markowitz, P.; Rutt, P.M.; Beard, K.; Anderson, B.D.; Baldwin, A.R.; Keane, D.; Manley, D.M.; Watson, J.W.; Zhang, W.M.; Kowalski, S.; Bertozzi, W.; Dodson, G.; Farkhondeh, M.; Dow, K.; Korsch, W.; Tieger, D.; Turchinetz, W.; Weinstein, L.; Gross, F.; Mougey, J.; Ulmer, P.; Whitney, R.; Reichelt, T.; Chang, C.C.; Kelly, J.J.; Payerle, T.; Cameron, J.; Ni, B.; Spraker, M.; Barkhuff, D.; Lourie, R.; Verst, S.V.; Hyde-Wright, C.; Jiang, W.-D.; Flanders, B.; Pella, P.; Arenhoevel, H.

1992-01-01

Nucleon form factors provide fundamental input for nuclear structure and quark models. Current knowledge of neutron form factors, particularly the electric form factor of the neutron, is insufficient to meet these needs. Developments of high-duty-factor accelerators and polarization-transfer techniques permit new experiments that promise results with small sensitivities to nuclear models. We review the current status of the field, our own work at the MIT/Bates linear accelerator, and future experimental efforts

Enhanced efficiency of plasma acceleration in the laser-induced cavity pressure acceleration scheme

Czech Academy of Sciences Publication Activity Database

Badziak, J.; Rosinski, M.; Jabłonski, S.; Pisarczyk, T.; Chodukowski, T.; Parys, P.; Raczka, P.; Krouský, Eduard; Ullschmied, Jiří; Liska, R.; Kucharik, M.

2015-01-01

Roč. 57, č. 1 (2015), 014007 ISSN 0741-3335 R&D Projects: GA MŠk(CZ) LC528; GA MŠk LM2010014 Institutional support: RVO:68378271 ; RVO:61389021 Keywords : laser ion acceleration * laser plasma * fast ignition * ion diagnostics * LICPA Subject RIV: BL - Plasma and Gas Discharge Physics; BH - Optics, Masers, Lasers (UFP-V) Impact factor: 2.404, year: 2015

2014 CERN Accelerator Schools: Plasma Wake Acceleration

CERN Multimedia

2014-01-01

A specialised school on Plasma Wake Acceleration will be held at CERN, Switzerland from 23-29 November, 2014.   This course will be of interest to staff and students in accelerator laboratories, university departments and companies working in or having an interest in the field of new acceleration techniques. Following introductory lectures on plasma and laser physics, the course will cover the different components of a plasma wake accelerator and plasma beam systems. An overview of the experimental studies, diagnostic tools and state of the art wake acceleration facilities, both present and planned, will complement the theoretical part. Topical seminars and a visit of CERN will complete the programme. Further information can be found at: http://cas.web.cern.ch/cas/PlasmaWake2014/CERN-advert.html http://indico.cern.ch/event/285444/

Deficiencies in both starch synthase IIIa and branching enzyme IIb lead to a significant increase in amylose in SSIIa-inactive japonica rice seeds.

Science.gov (United States)

Asai, Hiroki; Abe, Natsuko; Matsushima, Ryo; Crofts, Naoko; Oitome, Naoko F; Nakamura, Yasunori; Fujita, Naoko

2014-10-01

Starch synthase (SS) IIIa has the second highest activity of the total soluble SS activity in developing rice endosperm. Branching enzyme (BE) IIb is the major BE isozyme, and is strongly expressed in developing rice endosperm. A mutant (ss3a/be2b) was generated from wild-type japonica rice which lacks SSIIa activity. The seed weight of ss3a/be2b was 74-94% of that of the wild type, whereas the be2b seed weight was 59-73% of that of the wild type. There were significantly fewer amylopectin short chains [degree of polymerization (DP) ≤13] in ss3a/be2b compared with the wild type. In contrast, the amount of long chains (DP ≥25) connecting clusters of amylopectin in ss3a/be2b was higher than in the wild type and lower than in be2b. The apparent amylose content of ss3a/be2b was 45%, which was >1.5 times greater than that of either ss3a or be2b. Both SSIIIa and BEIIb deficiencies led to higher activity of ADP-glucose pyrophosphorylase (AGPase) and granule-bound starch synthase I (GBSSI), which partly explains the high amylose content in the ss3a/be2b endosperm. The percentage apparent amylose content of ss3a and ss3a/be2b at 10 days after flowering (DAF) was higher than that of the wild type and be2b. At 20 DAF, amylopectin biosynthesis in be2b and ss3a/be2b was not observed, whereas amylose biosynthesis in these lines was accelerated at 30 DAF. These data suggest that the high amylose content in the ss3a/be2b mutant results from higher amylose biosynthesis at two stages, up to 20 DAF and from 30 DAF to maturity. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Magnetogasdynamic Flow Acceleration in a Scramjet Nozzle

National Research Council Canada - National Science Library

Harrington, Brian

2004-01-01

.... The parameters of conductivity pattern and load factor are varied in both inviscid and viscous flow regimes with the intent of increasing axial force exerted on the flow through a scramjet accelerator...

Virtual Accelerator for Accelerator Optics Improvement

CERN Document Server

Yan Yi Ton; Decker, Franz Josef; Ecklund, Stanley; Irwin, John; Seeman, John; Sullivan, Michael K; Turner, J L; Wienands, Ulrich

2005-01-01

Through determination of all quadrupole strengths and sextupole feed-downs by fitting quantities derivable from precision orbit measurement, one can establish a virtual accelerator that matches the real accelerator optics. These quantities (the phase advances, the Green's functions, and the coupling eigen-plane ellipses tilt angles and axis ratios) are obtained by analyzing turn-by-turn Beam Position Monitor (BPM) data with a model-independent analysis (MIA). Instead of trying to identify magnet errors, a limited number of quadrupoles are chosen for optimized strength adjustment to improve the virtual accelerator optics and then applied to the real accelerator accordingly. These processes have been successfully applied to PEP-II rings for beta beating fixes, phase and working tune adjustments, and linear coupling reduction to improve PEP-II luminosity.

Tunnel flexibility effect on the ground surface acceleration response

Science.gov (United States)

Baziar, Mohammad Hassan; Moghadam, Masoud Rabeti; Choo, Yun Wook; Kim, Dong-Soo

2016-09-01

Flexibility of underground structures relative to the surrounding medium, referred to as the flexibility ratio, is an important factor that influences their dynamic interaction. This study investigates the flexibility effect of a box-shaped subway tunnel, resting directly on bedrock, on the ground surface acceleration response using a numerical model verified against dynamic centrifuge test results. A comparison of the ground surface acceleration response for tunnel models with different flexibility ratios revealed that the tunnels with different flexibility ratios influence the acceleration response at the ground surface in different ways. Tunnels with lower flexibility ratios have higher acceleration responses at short periods, whereas tunnels with higher flexibility ratios have higher acceleration responses at longer periods. The effect of the flexibility ratio on ground surface acceleration is more prominent in the high range of frequencies. Furthermore, as the flexibility ratio of the tunnel system increases, the acceleration response moves away from the free field response and shifts towards the longer periods. Therefore, the flexibility ratio of the underground tunnels influences the peak ground acceleration (PGA) at the ground surface, and may need to be considered in the seismic zonation of urban areas.

Persistent seroma after intraoperative placement of MammoSite for accelerated partial breast irradiation: Incidence, pathologic anatomy, and contributing factors

International Nuclear Information System (INIS)

Evans, Suzanne B.; Kaufman, Seth A.; Price, Lori Lyn; Cardarelli, Gene; Dipetrillo, Thomas A.; Wazer, David E.

2006-01-01

Purpose: To investigate the incidence of, and possible factors associated with, seroma formation after intraoperative placement of the MammoSite catheter for accelerated partial breast irradiation. Methods and Materials: This study evaluated 38 patients who had undergone intraoperative MammoSite catheter placement at lumpectomy or reexcision followed by accelerated partial breast irradiation with 34 Gy in 10 fractions. Data were collected regarding dosimetric parameters, including the volume of tissue enclosed by the 100%, 150%, and 200% isodose shells, dose homogeneity index, and maximal dose at the surface of the applicator. Clinical and treatment-related factors were analyzed, including patient age, patient weight, history of diabetes and smoking, use of reexcision, interval between surgery and radiotherapy, total duration of catheter placement, total excised specimen volume, and presence or absence of postprocedural infection. Seroma was verified by clinical examination, mammography, and/or ultrasonography. Persistent seroma was defined as seroma that was clinically detectable >6 months after radiotherapy completion. Results: After a median follow-up of 17 months, the overall rate of any detectable seroma was 76.3%. Persistent seroma (>6 months) occurred in 26 (68.4%) of 38 patients, of whom 46% experienced at least modest discomfort at some point during follow-up. Of these symptomatic patients, 3 required biopsy or complete cavity excision, revealing squamous metaplasia, foreign body giant cell reaction, fibroblasts, and active collagen deposition. Of the analyzed dosimetric, clinical, and treatment-related variables, only body weight correlated positively with the risk of seroma formation (p = 0.04). Postprocedural infection correlated significantly (p = 0.05) with a reduced risk of seroma formation. Seroma was associated with a suboptimal cosmetic outcome, because excellent scores were achieved in 61.5% of women with seroma compared with 83% without seroma

Analyzing radial acceleration with a smartphone acceleration sensor

Science.gov (United States)

Vogt, Patrik; Kuhn, Jochen

2013-03-01

This paper continues the sequence of experiments using the acceleration sensor of smartphones (for description of the function and the use of the acceleration sensor, see Ref. 1) within this column, in this case for analyzing the radial acceleration.

Caenorhabditis elegans DAF-16/FOXO Transcription Factor and Its Mammalian Homologs Associate with Age-Related Disease

NARCIS (Netherlands)

Hesp, K.; Smant, G.; Kammenga, J.E.

2015-01-01

The insulin/IGF-1 signaling pathway is evolutionarily conserved and its function is mediated largely by FOXO transcription factors. Reduced insulin/IGF-1 signaling leads to translocation of FOXO proteins from the cytoplasm to the nucleus where they activate a set of genes that mediate oxidative

High intensity proton linear accelerator for Neutron Science Project

International Nuclear Information System (INIS)

Mizumoto, Motoharu

1999-01-01

JAERI has been proposing the Neutron Science Project (NSP) which will be composed of a high intensity proton accelerator and various research facilities. With an energy of 1.5 GeV and a beam power of 8 MW, the accelerator is required for basic research fields and nuclear waste transmutation studies. The R and D work has been carried out for the components of the accelerator. In the low energy accelerator part, a beam test with an ion source and an RFQ has been performed with a current of 80 mA and a duty factor of 10% at an energy of 2 MeV. A 1 m long high power test model of DTL has been fabricated and tested with a duty factor of 20%. In the high energy accelerator part, a superconducting (SC) linac has been selected as a main option from 100 MeV to 1.5 GeV. A test stand for SC linac cavity with equipment of cryogenics, vacuum, RF source and cavity processing and cleaning system has been prepared to test the fabrication process and physics issues. The vertical tests of β = 0.5 (145 MeV) and β = 0.89 (1.1 GeV) single cell SC cavities have been made resulting in a maximum electric field strength of 44 MV/m and 47 MV/m at 2 K, respectively. (author)

Recent measurements of flame acceleration in semiconfined geometries

Energy Technology Data Exchange (ETDEWEB)

Abou-Arab, T.W. (King Fahd Univ. of Petroleum and Minerals, Dhahran (SA). Mechanical Engineering Dept.); Enayet, M.M.; Kamel, M.M. (Cairo Univ., Giza (EG). Mechanical Power Engineering Dept.)

1991-04-01

Turbulent premixed combustion under certain conditions may lead to large flame speeds sufficient to cause significant damage to nearby structures. Experiments, both large and small scale, have confirmed that obstructions cause severe flame acceleration to occur. In these cases, flame speeds as high as 800 ms{sup -1} may be achieved. In this work experimental investigation of some factors affecting flame acceleration in a semiconfined channel has been carried out. The experimental facility and the developed ionization gap measuring technique are also described. It has been found that the presence of obstacles, degree of confinement, height of fuel-air cloud (FAC), as well as fuel concentration gradient in the FAC have profound effects on the rate at which the flame accelerates. Finally, consideration of the flame acceleration as a possible mechanism for the transition to detonation will be discussed. (author).

Community Petascale Project for Accelerator Science and Simulation: Advancing Computational Science for Future Accelerators and Accelerator Technologies

Energy Technology Data Exchange (ETDEWEB)

Spentzouris, P.; /Fermilab; Cary, J.; /Tech-X, Boulder; McInnes, L.C.; /Argonne; Mori, W.; /UCLA; Ng, C.; /SLAC; Ng, E.; Ryne, R.; /LBL, Berkeley

2011-11-14

The design and performance optimization of particle accelerators are essential for the success of the DOE scientific program in the next decade. Particle accelerators are very complex systems whose accurate description involves a large number of degrees of freedom and requires the inclusion of many physics processes. Building on the success of the SciDAC-1 Accelerator Science and Technology project, the SciDAC-2 Community Petascale Project for Accelerator Science and Simulation (ComPASS) is developing a comprehensive set of interoperable components for beam dynamics, electromagnetics, electron cooling, and laser/plasma acceleration modelling. ComPASS is providing accelerator scientists the tools required to enable the necessary accelerator simulation paradigm shift from high-fidelity single physics process modeling (covered under SciDAC1) to high-fidelity multiphysics modeling. Our computational frameworks have been used to model the behavior of a large number of accelerators and accelerator R&D experiments, assisting both their design and performance optimization. As parallel computational applications, the ComPASS codes have been shown to make effective use of thousands of processors. ComPASS is in the first year of executing its plan to develop the next-generation HPC accelerator modeling tools. ComPASS aims to develop an integrated simulation environment that will utilize existing and new accelerator physics modules with petascale capabilities, by employing modern computing and solver technologies. The ComPASS vision is to deliver to accelerator scientists a virtual accelerator and virtual prototyping modeling environment, with the necessary multiphysics, multiscale capabilities. The plan for this development includes delivering accelerator modeling applications appropriate for each stage of the ComPASS software evolution. Such applications are already being used to address challenging problems in accelerator design and optimization. The ComPASS organization

Accelerator Service

International Nuclear Information System (INIS)

Champelovier, Y.; Ferrari, M.; Gardon, A.; Hadinger, G.; Martin, J.; Plantier, A.

1998-01-01

Since the cessation of the operation of hydrogen cluster accelerator in July 1996, four electrostatic accelerators were in operation and used by the peri-nuclear teams working in multidisciplinary collaborations. These are the 4 MV Van de Graaff accelerator, 2,5 MV Van de Graaff accelerator, 400 kV ion implanter as well as the 120 kV isotope separator

Performance of the intense pulsed neutron source accelerator system

International Nuclear Information System (INIS)

Potts, C.; Brumwell, F.; Rauchas, A.; Stipp, V.; Volk, G.

1983-01-01

The Intense Pulsed Neutron Source (IPNS) facility has now been operating in a routine way for outside users since November 1, 1981. From that date through December of 1982, the accelerator system was scheduled for neutron science for 4500 hours. During this time the accelerator achieved its short-term goals by delivering about 380,000,000 pulses of beam totaling over 6 x 10 20 protons. The changes in equipment and operating practices that evolved during this period of intense running are described. The intensity related instability threshold was increased by a factor of two and the accelerator beam current has been ion source limited. Plans to increase the accelerator intensity are also described. Initial operating results with a new H - ion source are discussed

Determination Of Output Factor For Photon Beam Of The Mitsubishi EXL-14 Linear Accelerator

International Nuclear Information System (INIS)

Nurman R; Sri-Inang S; Dani

2003-01-01

This paper describes the determination of output factor for 6 MV photon beam of The Mitsubishi EXL-14 linear accelerator teletherapy unit. Determination of percentage depth dose curve has been done using Wallhofer dosemeter at source to surface distance, SSD of 100 cm and field size of 10 cm x 10 cm. Measurement of output has been carried out using a 0.6 cc ionization chamber inside a water phantom at depth of 5 cm with source to surface distance, SSD of 100 cm for square fields ranging in size 4 cm x 4 cm up to 10 cm x 10 cm. Output for rectangular fields which equal to the equivalent square fields were also determined. The results obtained shows that the deviations of the output for 12 cm x 3 cm and 19 cm x 7 cm were higher than ±2% to the output of the equivalent square fields. (author)

Optimizing conditions for an accelerated leach test

International Nuclear Information System (INIS)

Pietrzak, R.F.; Fuhrmann, M.; Heiser, J.; Franz, E.M.; Colombo, P.

1988-01-01

An accelerated leach test for low-level radioactive waste forms is being developed to provide, in a short time, data that can be extrapolated to long time periods. The approach is to provide experimental conditions that will accelerate leaching without changing the dominant release mechanism. Experimental efforts have focused on combining individual factors that have been observed to accelerate leaching. These include elevated temperature, increased leachant volume, and reduced specimen size. The response of diffusion coefficients to various acceleration factors have been evaluated and provide information on experimental parameters that need to be optimized to increase leach rates. For example, these data show that large volumes of leachant are required when leaching portland cement waste forms at elevated temperatures because of high concentrations of dissolved species. Sr-85 leaching is particularly susceptible to suppression due to concentration effects while Cs-137 leaching is less so. Preliminary modeling using a diffusion mechanism (allowing for depletion) of a finite cylinder geometry indicates that during early portions of experiments (daily sampling intervals), leaching is diffusion controlled and more rapid than later in the same experiments (weekly or greater sampling intervals). For cement waste forms, this reduction in rate may be partially controlled by changes in physical structure and chemistry (sometimes related to environmental influences such as CO 2 ), but it is more likely associated with the duration of the sampling interval. 9 refs., 6 figs

The acceleration of particles by relativistic electron plasma waves driven by the optical mixing of laser light in a plasma

International Nuclear Information System (INIS)

Ebrahim, N.A.; Douglas, S.R.

1992-03-01

Electron acceleration by relativistic large-amplitude electron plasma waves is studied by theory and particle simulations. The maximum acceleration that can be obtained from this process depends on many different factors. This report presents a study of how these various factors impact on the acceleration mechanism. Although particular reference is made to the laser plasma beatwave concept, the study is equally relevant to the acceleration of particles in the plasma wakefield accelerator and the laser wakefield accelerator

SU-E-T-554: Comparison of Electron Disequilibrium Factor in External Photon Beams for Different Models of Linear Accelerators

International Nuclear Information System (INIS)

LIU, B; Zhu, T

2014-01-01

Purpose: The dose in the buildup region of a photon beam is usually determined by the transport of the primary secondary electrons and the contaminating electrons from accelerator head. This can be quantified by the electron disequilibrium factor, E, defined as the ratio between total dose and equilibrium dose (proportional to total kerma), E = 1 in regions beyond buildup region. Ecan be different among accelerators of different models and/or manufactures of the same machine. This study compares E in photon beams from different machine models/ Methods: Photon beam data such as fractional depth dose curve (FDD) and phantom scatter factors as a function of field size and phantom depth were measured for different Linac machines. E was extrapolated from these fractional depth dose data while taking into account inverse-square law. The ranges of secondary electron were chosen as 3 and 6 cm for 6 and 15 MV photon beams, respectively. The field sizes range from 2x2 to 40x40 cm 2 . Results: The comparison indicates the standard deviations of electron contamination among different machines are about 2.4 - 3.3% at 5 mm depth for 6 MV and 1.2 - 3.9% at 1 cm depth for 15 MV for the same field size. The corresponding maximum deviations are 3.0 - 4.6% and 2 - 4% for 6 and 15 MV, respectively. Both standard and maximum deviations are independent of field sizes in the buildup region for 6 MV photons, and slightly decreasing with increasing field size at depths up to 1 cm for 15 MV photons. Conclusion: The deviations of electron disequilibrium factor for all studied Linacs are less than 3% beyond the depth of 0.5 cm for the photon beams for the full range of field sizes (2-40 cm) so long as they are from the same manufacturer

Particle physicist's dreams about PetaelectronVolt laser plasma accelerators

International Nuclear Information System (INIS)

Vesztergombi, G.

2012-01-01

Present day accelerators are working well in the multi TeV energy scale and one is expecting exciting results in the coming years. Conventional technologies, however, can offer only incremental (factor 2 or 3) increase in beam energies which does not follow the usual speed of progress in the frontiers of high energy physics. Laser plasma accelerators theoretically provide unique possibilities to achieve orders of magnitude increases entering the PetaelectronVolt (PeV) energy range. It will be discussed what kind of new perspectives could be opened for the physics at this new energy scale. What type of accelerators would be required?.

Community petascale project for accelerator science and simulation: Advancing computational science for future accelerators and accelerator technologies

International Nuclear Information System (INIS)

Spentzouris, P.; Cary, J.; McInnes, L.C.; Mori, W.; Ng, C.; Ng, E.; Ryne, R.

2008-01-01

The design and performance optimization of particle accelerators are essential for the success of the DOE scientific program in the next decade. Particle accelerators are very complex systems whose accurate description involves a large number of degrees of freedom and requires the inclusion of many physics processes. Building on the success of the SciDAC-1 Accelerator Science and Technology project, the SciDAC-2 Community Petascale Project for Accelerator Science and Simulation (ComPASS) is developing a comprehensive set of interoperable components for beam dynamics, electromagnetics, electron cooling, and laser/plasma acceleration modelling. ComPASS is providing accelerator scientists the tools required to enable the necessary accelerator simulation paradigm shift from high-fidelity single physics process modeling (covered under SciDAC1) to high-fidelity multiphysics modeling. Our computational frameworks have been used to model the behavior of a large number of accelerators and accelerator R and D experiments, assisting both their design and performance optimization. As parallel computational applications, the ComPASS codes have been shown to make effective use of thousands of processors.

Energy calibration of the EGP-10M accelerator

International Nuclear Information System (INIS)

Simakov, S.P.; Spirin, V.I.; Trufanov, A.M.; Lovchikova, G.N.

1979-01-01

Energy calibration of an electrostatic charge exchange proton accelerator in the energy range from 3 to 9 MeV is described. The calibration has been measuring the (p, n) reaction thresholds on 13 C, 63 Cu, 27 Al, 60 Ni and 50 Cr nuclei. The neutron yield is measured by a long counter located at a distance of 10-15 cm from a target. Given also are the reaction thresholds and the values of the calibration factor determined according to the yield of neutrons from (p, n) reactions for the mentioned nuclei. The analysis of the resultant calibration curve of the EGP-10 M accelerator showed that errors are practically equal to the energy instability of the beam extracted from the accelerator and constitute approximately 0.06%. Variations of the calibration factor in the 3-9 MeV range are equal to 0.38%. The success in using this method is guaranteed due to the absence of isolated resonances in the (p, n) reaction cross-section above the threshold and emission of mainly S-neutrons in the exit channel

Harmonic ratcheting for fast acceleration

Science.gov (United States)

Cook, N.; Brennan, J. M.; Peggs, S.

2014-04-01

A major challenge in the design of rf cavities for the acceleration of medium-energy charged ions is the need to rapidly sweep the radio frequency over a large range. From low-power medical synchrotrons to high-power accelerator driven subcritical reactor systems, and from fixed focus alternating gradient accelerators to rapid cycling synchrotrons, there is a strong need for more efficient, and faster, acceleration of protons and light ions in the semirelativistic range of hundreds of MeV/u. A conventional way to achieve a large, rapid frequency sweep (perhaps over a range of a factor of 6) is to use custom-designed ferrite-loaded cavities. Ferrite rings enable the precise tuning of the resonant frequency of a cavity, through the control of the incremental permeability that is possible by introducing a pseudoconstant azimuthal magnetic field. However, rapid changes over large permeability ranges incur anomalous behavior such as the "Q-loss" and "f-dot" loss phenomena that limit performance while requiring high bias currents. Notwithstanding the incomplete understanding of these phenomena, they can be ameliorated by introducing a "harmonic ratcheting" acceleration scheme in which two or more rf cavities take turns accelerating the beam—one turns on when the other turns off, at different harmonics—so that the radio frequency can be constrained to remain in a smaller range. Harmonic ratcheting also has straightforward performance advantages, depending on the particular parameter set at hand. In some typical cases it is possible to halve the length of the cavities, or to double the effective gap voltage, or to double the repetition rate. This paper discusses and quantifies the advantages of harmonic ratcheting in general. Simulation results for the particular case of a rapid cycling medical synchrotron ratcheting from harmonic number 9 to 2 show that stability and performance criteria are met even when realistic engineering details are taken into consideration.

Advanced concepts for acceleration

International Nuclear Information System (INIS)

Keefe, D.

1986-07-01

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

Railgun accelerators for launching 0.1-g payloads at velocities greater than 150 km/s

International Nuclear Information System (INIS)

Hawke, R.S.

1979-01-01

The promise of an abundant energy supply has inspired many approaches to controlling thermal nuclear fusion. One approach to initiating fusion is to use a hypervelocity projectile to impact a deuterium--tritium (DT) pellet. For this purpose, magnetic accelerators have been propsed for accelerating macroparticles to velocities greater than 100 km/s. This paper summarizes a portion of a study that assesses the feasibility of accelerating a 0.1-g payload to a velocity of 150 km/s or more. In that study it was concluded that magnetic-gradient and railgun accelerators could achieve the goal. The critical factors that limit the design and operation of railgun accelerators are discussed. These factors are combined with a simulation code to assess potential railgun performance in this regime

Accelerating tube for the ''EG-1'' electrostatic accelerator

International Nuclear Information System (INIS)

Romanov, V.A.; Ivanov, V.V.; Krupnov, E.P.; Debin, V.K.; Dudkin, N.I.; Volodin, V.I.

1980-01-01

A design of an accelerating tube (AT) for an electrostatic accelerator of the EG-1 type is described. Primary consideration in the development of the AT has been given to increasing the electric strength of accelerating gaps, the vacuum conductivity and better insulator screening from charged particles. After AT vacuum and high-voltage ageing in the accelerator, a hydrogen ions beam of up to 80 μA has been produced. The beam was adequately shaped in the energy range from 1.8 to 5.0 MeV [ru

Target shape effects on monoenergetic GeV proton acceleration

Energy Technology Data Exchange (ETDEWEB)

Chen Min; Yu Tongpu; Pukhov, Alexander [Institut fuer Theoretische Physik I, Heinrich-Heine-Universitaet Duesseldorf, 40225 Duesseldorf (Germany); Sheng Zhengming, E-mail: pukhov@tp1.uni-duesseldorf.d [Department of Physics, Shanghai Jiao Tong University, Shanghai 200240 (China)

2010-04-15

When a circularly polarized laser pulse interacts with a foil target, there are three stages: pre-hole-boring, hole-boring and light sail acceleration. We study the electron and ion dynamics in the first stage and find the minimum foil thickness requirement for a given laser intensity. Based on this analysis, we propose using a shaped foil for ion acceleration, whose thickness varies transversely to match the laser intensity. Then, the target evolves into three regions: the acceleration, transparency and deformation regions. In the acceleration region, the target can be uniformly accelerated producing a mono-energetic and spatially collimated ion beam. Detailed numerical simulations are performed to check the feasibility and robustness of this scheme, such as the influence of shape factors and surface roughness. A GeV mono-energetic proton beam is observed in three-dimensional particle-in-cell simulations when a laser pulse with a focus intensity of 10{sup 22} W cm{sup -2} is used. The energy conversion efficiency of the laser pulse to the accelerated proton beam with the simulation parameters is more than 23%.

Target shape effects on monoenergetic GeV proton acceleration

International Nuclear Information System (INIS)

Chen Min; Yu Tongpu; Pukhov, Alexander; Sheng Zhengming

2010-01-01

When a circularly polarized laser pulse interacts with a foil target, there are three stages: pre-hole-boring, hole-boring and light sail acceleration. We study the electron and ion dynamics in the first stage and find the minimum foil thickness requirement for a given laser intensity. Based on this analysis, we propose using a shaped foil for ion acceleration, whose thickness varies transversely to match the laser intensity. Then, the target evolves into three regions: the acceleration, transparency and deformation regions. In the acceleration region, the target can be uniformly accelerated producing a mono-energetic and spatially collimated ion beam. Detailed numerical simulations are performed to check the feasibility and robustness of this scheme, such as the influence of shape factors and surface roughness. A GeV mono-energetic proton beam is observed in three-dimensional particle-in-cell simulations when a laser pulse with a focus intensity of 10 22 W cm -2 is used. The energy conversion efficiency of the laser pulse to the accelerated proton beam with the simulation parameters is more than 23%.

Gender by assertiveness interaction in delayed auditory feedback.

Science.gov (United States)

Elias, J W; Rosenzweig, C M; Dippel, R L

1981-04-01

The College Self-Expression and the Marlowe-Crowne Social Desirability Scales were given to 144 undergraduates. High (N; 10 M; 10 F) and Low (N; 10 M 10 F) Assertiveness Ss were given a DAF test with a 'Phonic Mirror" and the Stroop test (naming the color of a word printed in a different color). DAF performance did not differ among the 4 subgroups (M and F, High and Low Assertiveness), except that Low Assertiveness women showed significantly greater DAF interference than the other subgroups. There was no significant correlation between the continuous interference of the DAF vs the discontinuous of the Stroop test. The difference may reside in the time available and the consequent reduction in anxiety, for the next stimulus in the Stroop test. These data show that, under certain circumstances, personality factors such as assertiveness can interact with gender to affect speech fluency and production. The ability to overcome feedback-related disfluencies in speech may be partially aided by improvement in self-concept or specific training in such behaviors as assertiveness, and this may be more important for females than males.

Accelerant-related burns and drug abuse: Challenging combination.

Science.gov (United States)

Leung, Leslie T F; Papp, Anthony

2018-05-01

Accelerants are flammable substances that may cause explosion when added to existing fires. The relationships between drug abuse and accelerant-related burns are not well elucidated in the literature. Of these burns, a portion is related to drug manufacturing, which have been shown to be associated with increased burn complications. 1) To evaluate the demographics and clinical outcomes of accelerant-related burns in a Provincial Burn Centre. 2) To compare the clinical outcomes with a control group of non-accelerant related burns. 3) To analyze a subgroup of patients with history of drug abuse and drug manufacturing. Retrospective case control study. Patient data associated with accelerant-related burns from 2009 to 2014 were obtained from the British Columbia Burn Registry. These patients were compared with a control group of non-accelerant related burns. Clinical outcomes that were evaluated include inhalational injury, ICU length of stay, ventilator support, surgeries needed, and burn complications. Chi-square test was used to evaluate categorical data and Student's t-test was used to evaluate mean quantitative data with the p value set at 0.05. A logistic regression model was used to evaluate factors affecting burn complications. Accelerant-related burns represented 28.2% of all burn admissions (N=532) from 2009 to 2014. The accelerant group had higher percentage of patients with history of drug abuse and was associated with higher TBSA burns, ventilator support, ICU stay and pneumonia rates compared to the non-accelerant group. Within the accelerant group, there was no difference in clinical outcomes amongst people with or without history of drug abuse. Four cases were associated with methamphetamine manufacturing, all of which underwent ICU stay and ventilator support. Accelerant-related burns cause significant burden to the burn center. A significant proportion of these patients have history of drug abuse. Copyright © 2017 Elsevier Ltd and ISBI. All rights

CAS CERN Accelerator School superconductivity in particle accelerators

International Nuclear Information System (INIS)

Turner, S.

1989-01-01

One of the objectives of the CERN Accelerator School is to run courses on specialised topics in the particle accelerator field. The present volume contains the proceedings of one such course, this time organized in conjunction with the Deutsches Elektronen Synchrotron (DESY) on the subject of superconductivity in particle accelerators. This course reflects the very considerable progress made over the last few years in the use of the technology for the magnet and radio-frequency systems of many large and small accelerators already in use or nearing completion, while also taking account of the development work now going on for future machines. The lectures cover the theory of superconductivity, cryogenics and accelerator magnets and cavities, while the seminars include superfluidity, superconductors, special magnets and the prospects for high-temperature superconductors. (orig.)

Model for initiation of quality factor degradation at high accelerating fields in superconducting radio-frequency cavities

International Nuclear Information System (INIS)

Dzyuba, A; Romanenko, A; Cooley, L D

2010-01-01

A model for the onset of the reduction in superconducting radio-frequency (SRF) cavity quality factor, the so-called Q-drop, at high accelerating electric fields is presented. Since magnetic fields at the cavity equator are tied to accelerating electric fields by a simple geometric factor, the onset of magnetic flux penetration determines the onset of Q-drop. We consider breakdown of the surface barrier at triangular grooves to predict the magnetic field of first flux penetration H pen . Such defects were argued to be the worst case by Buzdin and Daumens (1998 Physica C 294 257), whose approach, moreover, incorporates both the geometry of the groove and local contamination via the Ginzburg-Landau parameter κ. Since previous Q-drop models focused on either topography or contamination alone, the proposed model allows new comparisons of one effect in relation to the other. The model predicts equivalent reduction of H pen when either roughness or contamination were varied alone, so smooth but dirty surfaces limit cavity performance about as much as rough but clean surfaces do. Still lower H pen was predicted when both effects were combined, i.e. contamination should exacerbate the negative effects of roughness and vice versa. To test the model with actual data, coupons were prepared by buffered chemical polishing and electropolishing, and stylus profilometry was used to obtain distributions of angles. From these data, curves for surface resistance generated by simple flux flow as a function of magnetic field were generated by integrating over the distribution of angles for reasonable values of κ. This showed that combined effects of roughness and contamination indeed reduce the Q-drop onset field by ∼ 20%, and that contamination contributes to Q-drop as much as roughness. The latter point may be overlooked by SRF cavity research, since access to the cavity interior by spectroscopy tools is very difficult, whereas optical images have become commonplace. The model

Model for initiation of quality factor degradation at high accelerating fields in superconducting radio-frequency cavities

Science.gov (United States)

Dzyuba, A.; Romanenko, A.; Cooley, L. D.

2010-12-01

A model for the onset of the reduction in superconducting radio-frequency (SRF) cavity quality factor, the so-called Q-drop, at high accelerating electric fields is presented. Since magnetic fields at the cavity equator are tied to accelerating electric fields by a simple geometric factor, the onset of magnetic flux penetration determines the onset of Q-drop. We consider breakdown of the surface barrier at triangular grooves to predict the magnetic field of first flux penetration Hpen. Such defects were argued to be the worst case by Buzdin and Daumens (1998 Physica C 294 257), whose approach, moreover, incorporates both the geometry of the groove and local contamination via the Ginzburg-Landau parameter κ. Since previous Q-drop models focused on either topography or contamination alone, the proposed model allows new comparisons of one effect in relation to the other. The model predicts equivalent reduction of Hpen when either roughness or contamination were varied alone, so smooth but dirty surfaces limit cavity performance about as much as rough but clean surfaces do. Still lower Hpen was predicted when both effects were combined, i.e. contamination should exacerbate the negative effects of roughness and vice versa. To test the model with actual data, coupons were prepared by buffered chemical polishing and electropolishing, and stylus profilometry was used to obtain distributions of angles. From these data, curves for surface resistance generated by simple flux flow as a function of magnetic field were generated by integrating over the distribution of angles for reasonable values of κ. This showed that combined effects of roughness and contamination indeed reduce the Q-drop onset field by ~ 20%, and that contamination contributes to Q-drop as much as roughness. The latter point may be overlooked by SRF cavity research, since access to the cavity interior by spectroscopy tools is very difficult, whereas optical images have become commonplace. The model was

Study on the limiting acceleration rate in the VLEPP linear accelerator

International Nuclear Information System (INIS)

Balakin, V.E.; Brezhnev, O.N.; Zakhvatkin, M.N.

1987-01-01

To realize the design of colliding linear electron-positron beams it is necessary to solve the radical problem of production of accelerating structure with acceleration rate of approximately 100 MeV/m which can accelerate 10 12 particles in a bunch. Results of experimental studies of the limiting acceleration rate in the VLEPP accelerating structure are presented. Accelerating sections of different length were tested. When testing sections 29 cm long the acceleration rate of 55 MeV/m was attained, and for 1 m section the value reached 40 MeV/m. The maximum rate of acceleration (90 MeV/m) was attained when electric field intensity on the structure surface constituted more than 150 MV/m

PONDEROMOTIVE ACCELERATION IN CORONAL LOOPS

International Nuclear Information System (INIS)

Dahlburg, R. B.; Obenschain, K.; Laming, J. M.; Taylor, B. D.

2016-01-01

Ponderomotive acceleration has been asserted to be a cause of the first ionization potential (FIP) effect, the well-known enhancement in abundance by a factor of 3–4 over photospheric values of elements in the solar corona with FIP less than about 10 eV. It is shown here by means of numerical simulations that ponderomotive acceleration occurs in solar coronal loops, with the appropriate magnitude and direction, as a “by-product” of coronal heating. The numerical simulations are performed with the HYPERION code, which solves the fully compressible three-dimensional magnetohydrodynamic equations including nonlinear thermal conduction and optically thin radiation. Numerical simulations of coronal loops with an axial magnetic field from 0.005 to 0.02 T and lengths from 25,000 to 75,000 km are presented. In the simulations the footpoints of the axial loop magnetic field are convected by random, large-scale motions. There is a continuous formation and dissipation of field-aligned current sheets, which act to heat the loop. As a consequence of coronal magnetic reconnection, small-scale, high-speed jets form. The familiar vortex quadrupoles form at reconnection sites. Between the magnetic footpoints and the corona the reconnection flow merges with the boundary flow. It is in this region that the ponderomotive acceleration occurs. Mirroring the character of the coronal reconnection, the ponderomotive acceleration is also found to be intermittent.

PONDEROMOTIVE ACCELERATION IN CORONAL LOOPS

Energy Technology Data Exchange (ETDEWEB)

Dahlburg, R. B.; Obenschain, K. [LCP and FD, Naval Research Laboratory, Washington, DC 20375 (United States); Laming, J. M. [Space Science Division, Naval Research Laboratory, Washington, DC 20375 (United States); Taylor, B. D. [AFRL Eglin AFB, Pensacola, FL 32542 (United States)

2016-11-10

Ponderomotive acceleration has been asserted to be a cause of the first ionization potential (FIP) effect, the well-known enhancement in abundance by a factor of 3–4 over photospheric values of elements in the solar corona with FIP less than about 10 eV. It is shown here by means of numerical simulations that ponderomotive acceleration occurs in solar coronal loops, with the appropriate magnitude and direction, as a “by-product” of coronal heating. The numerical simulations are performed with the HYPERION code, which solves the fully compressible three-dimensional magnetohydrodynamic equations including nonlinear thermal conduction and optically thin radiation. Numerical simulations of coronal loops with an axial magnetic field from 0.005 to 0.02 T and lengths from 25,000 to 75,000 km are presented. In the simulations the footpoints of the axial loop magnetic field are convected by random, large-scale motions. There is a continuous formation and dissipation of field-aligned current sheets, which act to heat the loop. As a consequence of coronal magnetic reconnection, small-scale, high-speed jets form. The familiar vortex quadrupoles form at reconnection sites. Between the magnetic footpoints and the corona the reconnection flow merges with the boundary flow. It is in this region that the ponderomotive acceleration occurs. Mirroring the character of the coronal reconnection, the ponderomotive acceleration is also found to be intermittent.

Particle-accelerator decommissioning

International Nuclear Information System (INIS)

Opelka, J.H.; Mundis, R.L.; Marmer, G.J.; Peterson, J.M.; Siskind, B.; Kikta, M.J.

1979-12-01

Generic considerations involved in decommissioning particle accelerators are examined. There are presently several hundred accelerators operating in the United States that can produce material containing nonnegligible residual radioactivity. Residual radioactivity after final shutdown is generally short-lived induced activity and is localized in hot spots around the beam line. The decommissioning options addressed are mothballing, entombment, dismantlement with interim storage, and dismantlement with disposal. The recycle of components or entire accelerators following dismantlement is a definite possibility and has occurred in the past. Accelerator components can be recycled either immediately at accelerator shutdown or following a period of storage, depending on the nature of induced activation. Considerations of cost, radioactive waste, and radiological health are presented for four prototypic accelerators. Prototypes considered range from small accelerators having minimal amounts of radioactive mmaterial to a very large accelerator having massive components containing nonnegligible amounts of induced activation. Archival information on past decommissionings is presented, and recommendations concerning regulations and accelerator design that will aid in the decommissioning of an accelerator are given

Quantitative accelerated degradation testing: Practical approaches

International Nuclear Information System (INIS)

Mohammadian, S. Hossein; Ait-Kadi, Daoud; Routhier, Francois

2010-01-01

The concept of accelerated testing by tracking degradation of samples over test time needs to be developed for reliability estimation. This paper aims at proposing practical approaches to conduct accelerated degradation testing on new and available used samples. For this purpose, product failure is related to a suitable physical property. Then, its failure time is defined as the expected time in which its property reaches the critical level. Degradation model of field samples returned from service due to a degrading failure mode has been estimated based on the least square method, and available gap between manufacturer criterion and user's claim (to report a failure) has also been discussed. For a product under some stresses, a general formula has been proposed by the superposition principle in order to estimate its degradation for independent and dependent failure modes. If used samples are available, and acceleration factor of the related test is unknown, partial aging method has been presented to considerably shorten the test time.

Study of vibrational modes and specific heat of wurtzite phase of BN

Energy Technology Data Exchange (ETDEWEB)

Singh, Daljit, E-mail: daljit.jt@gmail.com; Sinha, M. M. [Department of Physics, SLIET, Longowal (India)

2016-05-06

In these days of nanotechnology the materials like BN is of utmost importance as in hexagonal phase it is among hardest materials. The phonon mode study of the materials is most important factor to find structural and thermodynamcal properties. To study the phonons de launey angular force (DAF) constant model is best suited as it involves many particle interactions. Therefore in this presentation we have studied the lattice dynamical properties and specific heat of BN in wurtzite phase using DAF model. The obtained results are in excellent agreement with existing results.

Study of vibrational modes and specific heat of wurtzite phase of BN

International Nuclear Information System (INIS)

Singh, Daljit; Sinha, M. M.

2016-01-01

In these days of nanotechnology the materials like BN is of utmost importance as in hexagonal phase it is among hardest materials. The phonon mode study of the materials is most important factor to find structural and thermodynamcal properties. To study the phonons de launey angular force (DAF) constant model is best suited as it involves many particle interactions. Therefore in this presentation we have studied the lattice dynamical properties and specific heat of BN in wurtzite phase using DAF model. The obtained results are in excellent agreement with existing results.

Concentrated Light for Accelerated Photo Degradation of Polymer Materials

DEFF Research Database (Denmark)

Madsen, Morten Vesterager; Tromholt, Thomas; Norrman, Kion

2013-01-01

Concentrated light is used to perform photochemical degradation of polymer solar cell materials with acceleration factors up to 1200. At constant temperature the photon efficiency in regards to photo degradation is constant for 1–150 suns and oxygen diffusion rates are not a limiting factor...

Medium-Term Stability of the Photon Beam Energy of An Elekta CompactTM Linear Accelerator Based on Daily Measurements of Beam Quality Factor

Directory of Open Access Journals (Sweden)

Mohammad Amin Mosleh-Shirazi

2016-04-01

Full Text Available Introduction In this study, we aimed to assess the medium-term energy stability of a 6MV Elekta CompactTM linear accelerator. To the best of our knowledge, this is the first published article to evaluate this linear accelerator in terms of energy stability. As well as investigating the stability of the linear accelerator energy over a period of several weeks, the results will be useful for estimation of the required tolerance values for the beam quality factor (BQF of the PTW QUICKCHECK weblineTM (QCW daily checking device. Materials and Methods Over a 13 week period of routine clinical service, 52 daily readings of BQF were taken and then analyzed for a 10×10 cm2 field. Results No decreasing or increasing trend in BQF was observed over the study period. The mean BQF value was estimated at 5.4483 with a standard deviation (SD of 0.0459 (0.8%. The mean value was only 0.1% different from the baseline value. Conclusion The results of this medium-term stability study of the Elekta Compact linear accelerator energy showed that 96.2% of the observed BQF values were within ±1.3% of the baseline value. This can be considered to be within the recommended tolerance for linear accelerator photon beam energy. If an approach of applying ±3 SD is taken, the tolerance level for BQF may be suggested to be set at ±2.5%. However, further research is required to establish a relationship between BQF value and the actual changes in beam energy and penetrative quality.

How a Mutation that Slows Aging Can Also Disproportionately Extend End-of-Life Decrepitude

Directory of Open Access Journals (Sweden)

Katie Podshivalova

2017-04-01

Full Text Available Summary: The goal of aging research is to extend healthy, active life. For decades, C. elegans daf-2 insulin/insulin-like growth factor 1 (IGF-1 receptor mutants have served as a model for extended lifespan and youthfulness. However, a recent report suggested that their longevity is associated with an undesirable phenotype: a disproportionately long period of decrepitude at the end of life. In the human population, such an outcome would be a burden to society, bringing into question the relevance of daf-2 mutants as a model for life extension. However, here we report that, following an extended period of movement, daf-2 mutants survive longer in a decrepit state because of a beneficial trait: they are resistant to colonization of the digestive tract by dietary bacteria, a condition that leads to premature death in the wild-type and prevents their manifestation of decrepitude. If bacterial colonization is prevented, then daf-2 mutants lead both chronologically and proportionately healthier lives relative to the wild-type. : Podshivalova et al. show that long-lived C. elegans insulin/IGF-1 receptor mutants remain active longer but then resist bacterially induced mortality, allowing them to survive into a state of end-of-life decrepitude. Thus, changes that slow aging and also prevent an age-associated catastrophe can extend both the youthful and infirm periods of life. Keywords: aging, lifespan, healthspan, daf-2, mortality, IGF-1, pathogenesis

Source-to-accelerator quadrupole matching section for a compact linear accelerator

Science.gov (United States)

Seidl, P. A.; Persaud, A.; Ghiorso, W.; Ji, Q.; Waldron, W. L.; Lal, A.; Vinayakumar, K. B.; Schenkel, T.

2018-05-01

Recently, we presented a new approach for a compact radio-frequency (RF) accelerator structure and demonstrated the functionality of the individual components: acceleration units and focusing elements. In this paper, we combine these units to form a working accelerator structure: a matching section between the ion source extraction grids and the RF-acceleration unit and electrostatic focusing quadrupoles between successive acceleration units. The matching section consists of six electrostatic quadrupoles (ESQs) fabricated using 3D-printing techniques. The matching section enables us to capture more beam current and to match the beam envelope to conditions for stable transport in an acceleration lattice. We present data from an integrated accelerator consisting of the source, matching section, and an ESQ doublet sandwiched between two RF-acceleration units.

Commissioning the GTA accelerator

International Nuclear Information System (INIS)

Sander, O.R.; Atkins, W.H.; Bolme, G.O.; Bowling, S.; Brown, S.; Cole, R.; Gilpatrick, J.D.; Garnett, R.; Guy, F.W.; Ingalls, W.B.; Johnson, K.F.; Kerstiens, D.; Little, C.; Lohsen, R.A.; Lloyd, S.; Lysenko, W.P.; Mottershead, C.T.; Neuschaefer, G.; Power, J.; Rusthoi, D.P.; Sandoval, D.P.; Stevens, R.R.; Vaughn, G.; Wadlinger, E.A.; Connolly, R.; Weiss, R.; Saadatmand, K.

1992-01-01

The Ground Test Accelerator (GTA) is being used to resolve the physics and engineering issues related to accelerating, focusing, and steering a high-brightness, high-current H - beam and then neutralizing it. The goal is to produce a 24 MeV, 50 mA device with a 2% duty factor. Specific features of the GTA -- injector, beam optics, rf linac structures, diagnostics, control and rf power systems are described. The first four steps in commissioning have been completed. The RFQ predicted and measured performances are in good agreement; however, the transmission is lower than specifications. Input emittance is larger than design specifications and increases the effects of image charge and multipoles. Displacement of steering magnets in either the horizontal or vertical plane caused beam displacements in both planes. It is suspected that quadrupole rotation is the cause of the coupled motion. 9 figs., 5 tabs., 11 refs

Electrostatic accelerators

CERN Document Server

Hinterberger, F

2006-01-01

The principle of electrostatic accelerators is presented. We consider Cockcroft– Walton, Van de Graaff and Tandem Van de Graaff accelerators. We resume high voltage generators such as cascade generators, Van de Graaff band generators, Pelletron generators, Laddertron generators and Dynamitron generators. The speci c features of accelerating tubes, ion optics and methods of voltage stabilization are described. We discuss the characteristic beam properties and the variety of possible beams. We sketch possible applications and the progress in the development of electrostatic accelerators.

A preliminary design of the collinear dielectric wakefield accelerator

Energy Technology Data Exchange (ETDEWEB)

Zholents, A.; Gai, W.; Doran, S.; Lindberg, R.; Power, J.G.; Strelnikov, N.; Sun, Y.; Trakhtenberg, E.; Vasserman, I. [ANL, Argonne, IL 60439 (United States); Jing, C.; Kanareykin, A.; Li, Y. [Euclid Techlabs LLC, Solon, OH 44139 (United States); Gao, Q. [Tsinghua University, Beijing (China); Shchegolkov, D.Y.; Simakov, E.I. [LANL, Los Alamos, NM 87545 (United States)

2016-09-01

A preliminary design of the multi-meter long collinear dielectric wakefield accelerator that achieves a highly efficient transfer of the drive bunch energy to the wakefields and to the witness bunch is considered. It is made from ~0.5 m long accelerator modules containing a vacuum chamber with dielectric-lined walls, a quadrupole wiggler, an rf coupler, and BPM assembly. The single bunch breakup instability is a major limiting factor for accelerator efficiency, and the BNS damping is applied to obtain the stable multi-meter long propagation of a drive bunch. Numerical simulations using a 6D particle tracking computer code are performed and tolerances to various errors are defined.

Reference dosimetry data and modeling challenges for Elekta accelerators based on IROC-Houston site visit data.

Science.gov (United States)

Kerns, James R; Followill, David S; Lowenstein, Jessica; Molineu, Andrea; Alvarez, Paola; Taylor, Paige A; Kry, Stephen F

2018-03-14

Reference dosimetry data can provide an independent second check of acquired values when commissioning or validating a treatment planning system (TPS). The Imaging and Radiation Oncology Core at Houston (IROC-Houston) has measured numerous linear accelerators throughout its existence. The results of those measurements are given here, comparing accelerators and the agreement of measurement versus institutional TPS calculations. Data from IROC-Houston on-site reviews from 2000 through 2014 were analyzed for all Elekta accelerators, approximately 50. For each, consistent point dose measurements were conducted for several basic parameters in a water phantom, including percentage depth dose, output factors, small-field output factors, off-axis factors, and wedge factors. The results were compared by accelerator type independently for 6, 10, 15, and 18 MV. Distributions of the measurements for each parameter are given, providing the mean and standard deviation. Each accelerator's measurements were also compared to its corresponding TPS calculation from the institution to determine the level of agreement, as well as determining which dosimetric parameters were most often in error. Accelerators were grouped by head type and reference dosimetric values were compiled. No class of linac had better overall agreement with its TPS, but percentage depth dose and output factors commonly agreed well, while small-field output factors, off-axis factors, and wedge factors often disagreed substantially from their TPS calculations. Reference data has been collected and analyzed for numerous Elekta linacs, which provide an independent way for a physicist to double-check their own measurements to prevent gross treatment errors. In addition, treatment planning parameters more often in error have been highlighted, providing practical caution for physicists commissioning treatment planning systems for Elekta linacs. © 2018 American Association of Physicists in Medicine.

Acceleration of 14C beams in electrostatic accelerators

International Nuclear Information System (INIS)

Rowton, L.J.; Tesmer, J.R.

1981-01-01

Operational problems in the production and acceleration of 14 C beams for nuclear structure research in Los Alamos National Laboratory's Van de Graaff accelerators are discussed. Methods for the control of contamination in ion sources, accelerators and personnel are described. Sputter source target fabrication techniques and the relative beam production efficiencies of various types of bound particulate carbon sputter source targets are presented

Multiperiodic accelerator structures for linear particle accelerators

International Nuclear Information System (INIS)

Tran, D.T.

1975-01-01

High efficiency linear accelerator structures, comprised of a succession of cylindrical resonant cavities for acceleration, are described. Coupling annular cavities are located at the periphery, each being coupled to two adjacent cylindrical cavities. (auth)

Choice of initial operating parameters for high average current linear accelerators

International Nuclear Information System (INIS)

Batchelor, K.

1976-01-01

In designing an accelerator for high currents it is evident that beam losses in the machine must be minimized, which implies well matched beams, and that adequate acceptance under severe space charge conditions must be met. This paper investigates the input parameters to an Alvarez type drift-tube accelerator resulting from such factors

Beam transport through electrostatic accelerators and matching into post accelerators

International Nuclear Information System (INIS)

Larson, J.D.

1986-01-01

Ion beam transport through electrostatic acceleration is briefly reviewed. Topics discussed include injection, matching into the low-energy acceleration stage, matching from the terminal stripper into the high-energy stage, transport to a post accelerator, space charge, bunching isochronism, dispersion and charge selection. Beam transport plans for the proposed Vivitron accelerator are described. (orig.)

Induction Acceleration of a Single RF Bunch in the KEK PS

CERN Document Server

Takayama, Ken; Arakida, Yoshio; Horioka, Kazuhiko; Igarashi, Susumu; Iwashita, Taiki; Kawasaki, Atsushi; Kishiro, Junichi; Kono, Tadaaki; Koseki, Kunio; Nakamura, Eiji; Sakuda, Makoto; Sato, Hikaru; Shiho, Makoto; Shimosaki, Yoshito; Shirakata, Masashi; Sueno, Tsuyoshi; Tokuchi, Akira; Torikai, Kota; Toyama, Takeshi; Wake, Masayoshi; Watanabe, Masao; Yamane, Isao

2005-01-01

A single bunch trapped in an RF bucket was accelerated by induction devices from 500 MeV to 8GeV beyond transition energy in the KEK-PS. This is the first demonstration of induction acceleration in a high energy circular ring. The acceleration was confirmed by measuring a temporal evolution of the RF phase through an entire acceleration.* Key devices in an induction acceleration system are an induction accelerating cavity capable of generating an induced voltage of 2kV/cell, a pulse modulator to drive the cavity (switching driver), and a DSP system to control gate signals for switching. Their remarkable characteristics are its repetition ratio of about 1MHz and duty factor of 50%. All devices have been newly developed at KEK so as to meet this requirement. The pulse modulator employing MOSFETs as switching elements is connected with the accelerating cavity through a long transmission cable in order to avoid a high-dose irradiation in the accelerator tunnel. The induction system has been running beyond more th...

Co-delivery of a growth factor and a tissue-protective molecule using elastin biopolymers accelerates wound healing in diabetic mice.

Science.gov (United States)

Devalliere, Julie; Dooley, Kevin; Hu, Yong; Kelangi, Sarah S; Uygun, Basak E; Yarmush, Martin L

2017-10-01

Growth factor therapy is a promising approach for chronic diabetic wounds, but strategies to efficiently and cost-effectively deliver active molecules to the highly proteolytic wound environment remain as major obstacles. Here, we re-engineered keratinocyte growth factor (KGF) and the cellular protective peptide ARA290 into a protein polymer suspension with the purpose of increasing their proteolytic resistance, thus their activity in vivo. KGF and ARA290 were fused with elastin-like peptide (ELP), a protein polymer derived from tropoelastin, that confers the ability to separate into a colloidal suspension of liquid-like coacervates. ELP fusion did not diminish peptides activities as demonstrated by ability of KGF-ELP to accelerate keratinocyte proliferation and migration, and ARA290-ELP to protect cells from apoptosis. We examined the healing effect of ARA290-ELP and KGF-ELP alone or in combination, in a full-thickness diabetic wound model. In this model, ARA290-ELP was found to accelerate healing, notably by increasing angiogenesis in the wound bed. We further showed that co-delivery of ARA290 and KGF, with the 1:4 KGF-ELP to ARA290-ELP ratio, was the most effective wound treatment with the fastest healing rate, the thicker granulation tissue and regenerated epidermis after 28 days. Overall, this study shows that ARA290-ELP and KGF-ELP constitute promising new therapeutics for treatment of chronic wounds. Copyright © 2017 Elsevier Ltd. All rights reserved.

RF Accelerating Structure for the Muon Cooling Experiment

International Nuclear Information System (INIS)

Corlett, J.; Green, M.; Li, D.; Holtkamp, N.; Moretti, A.; Kirk, H. G.; Palmer, R. B.; Zhao, Y.; Summers, D.

1999-01-01

The ionization cooling of muons requires longitudinal acceleration of the muons after scattering in a hydrogen target. In order to maximize the accelerating voltage, they propose using linear accelerating structures with cells bounded by thin beryllium metal foils. this produces an on-axis field equivalent to the maximum surface field, whereas with beam-pipes the accelerating field is approximately half that of the peak surface field in the cavity. The muons interact only weakly with the thin foils. A π/2 interleaved cavity structure has been chosen, with alternate cells coupled together externally, and the two groups of cells fed in quadrature. At present they are considering an operating temperature of 77K to gain a factor of at least two in Q-value over room temperature. They will describe the design of the π/2 interleaved cavity structure, design of an alternative π-mode open structure, preliminary experimental results from a low-power test cavity, and plans for high-power testing

Present and future prospects of accelerator mass spectrometry

International Nuclear Information System (INIS)

Kutschera, W.

1987-04-01

Accelerator Mass Spectrometry (AMS) has become a powerful technique for measuring extremely low abundances (10 -10 to 10 -15 relative to stable isotopes) of long-lived radioisotopes with half-lives in the range from 10 2 to 10 8 years. With a few exceptions, tandem accelerators turned out to be the most useful instruments for AMS measurements. Both natural (mostly cosmogenic) and man-made (anthropogenic) radioisotopes are studied with this technique. In some cases very low concentrations of stable isotope are also measured. Applications of AMS cover a large variety of fields including anthropology, archaeology, oceanography, hydrology, climatology, volcanology, minerals exploration, cosmochemistry, meteoritics, glaciology, sedimentary processes, geochronology, environmental physics, astrophysics, nuclear and particle physics. Present and future prospects of AMS are discussed as an interplay between the continuous development of new techniques and the investigation of problems in the above mentioned fields. Typical factors to be considered are energy range and type of accelerator, and the possibilities of dedicated versus partial use of new or existing accelerators

Microdroplet fusion mass spectrometry: accelerated kinetics of acid-induced chlorophyll demetallation.

Science.gov (United States)

Lee, Jae Kyoo; Nam, Hong Gil; Zare, Richard N

2017-01-01

Kinetics of acid-induced chlorophyll demetallation was recorded in microdroplets by fusing a stream of microdroplets containing 40 µM chlorophyll a or b dissolved in methanol with a stream of aqueous microdroplets containing 35 mM hydrochloric acid (pH = 1·46). The kinetics of the demetallation of chlorophyll in the fused microdroplets (14 ± 6 µm diameter; 84 ± 18 m s-1 velocity) was recorded by controlling the traveling distance of the fused microdroplets between the fusion region and the inlet of a mass spectrometer. The rate of acid-induced chlorophyll demetallation was about 960 ± 120 times faster in the charged microdroplets compared with that reported in bulk solution. If no voltage was applied to the sprayed microdroplets, then the acceleration factor was about 580 ± 90, suggesting that the applied voltage is not a major factor determining the acceleration. Chlorophyll a was more rapidly demetallated than chlorophyll b by a factor of ~26 in bulk solution and ~5 in charged microdroplets. The demetallation kinetics was second order in the H+ concentration, but the acceleration factor of microdroplets compared with bulk solution appeared to be unchanged in going from pH = 1·3 to 7·0. The water:methanol ratio of the fused microdroplets was varied from 7:3 to 3:7 causing an increase in the reaction rate of chlorophyll a demetallation by 20%. This observation demonstrates that the solvent composition, which has different evaporation rates, does not significantly affect the acceleration. We believe that a major portion of the acceleration can be attributed to confinement effects involving surface reactions rather than either to evaporation of solvents or to the introduction of charges to the microdroplets.

Can Accelerators Accelerate Learning?

International Nuclear Information System (INIS)

Santos, A. C. F.; Fonseca, P.; Coelho, L. F. S.

2009-01-01

The 'Young Talented' education program developed by the Brazilian State Funding Agency (FAPERJ)[1] makes it possible for high-schools students from public high schools to perform activities in scientific laboratories. In the Atomic and Molecular Physics Laboratory at Federal University of Rio de Janeiro (UFRJ), the students are confronted with modern research tools like the 1.7 MV ion accelerator. Being a user-friendly machine, the accelerator is easily manageable by the students, who can perform simple hands-on activities, stimulating interest in physics, and getting the students close to modern laboratory techniques.

Can Accelerators Accelerate Learning?

Science.gov (United States)

Santos, A. C. F.; Fonseca, P.; Coelho, L. F. S.

2009-03-01

The 'Young Talented' education program developed by the Brazilian State Funding Agency (FAPERJ) [1] makes it possible for high-schools students from public high schools to perform activities in scientific laboratories. In the Atomic and Molecular Physics Laboratory at Federal University of Rio de Janeiro (UFRJ), the students are confronted with modern research tools like the 1.7 MV ion accelerator. Being a user-friendly machine, the accelerator is easily manageable by the students, who can perform simple hands-on activities, stimulating interest in physics, and getting the students close to modern laboratory techniques.

Accelerating polarized beams at the AGS

International Nuclear Information System (INIS)

Roser, T.

1995-01-01

The acceleration of polarized beams in circular accelerators is complicated by the presence of numerous depolarizing resonances. During acceleration, a depolarizing resonance is crossed whenever the spin precession frequency equals the frequency with which spin-perturbing magnetic fields are encountered. There are two main types of depolarizing resonances corresponding to the possible sources of such fields: imperfection resonances, which are driven by magnet errors and misalignments, and intrinsic resonances, driven by the focusing fields. The resonance conditions are usually expressed in terms of the spin tune ν s , which is defined as the number of spin precessions per revolution. For an ideal planar accelerator, where orbiting particles experience only the vertical guide field, the spin tune is equal to Gγ, where G = 1.7928 is the anomalous magnetic moment of the proton and γ is the relativistic Lorentz factor. The resonance condition for imperfection depolarizing resonances arise when ν s = Gγ = n, where n is an integer. Imperfection resonances are therefore separated by only 523 MeV energy steps. The condition for intrinsic resonances is ν s = Gγ = kP ± ν y , where k is an integer, ν y is the vertical betatron tune and P is the superperiodicity. For the AGS, P = 12 and ν y ∼ 8.8. For most of the time during the acceleration cycle, the precession direction, or stable spin direction, coincides with the main vertical magnetic field. Close to a resonance, the stable spin direction is perturbed away from the vertical direction by the resonance driving fields. When a polarized beam is accelerated through an isolated resonance, the final polarization can be calculated analytically

Technology and applications of electron accelerator

International Nuclear Information System (INIS)

Natsir, M.

1998-01-01

Technology of electron accelerator have been developed so fast in advanced countries. It was applied in the research and development (R and D) and comercially in various industries. The industries applying electron accelerator includes polymers industry, sterilization of medical tools, material surface modification, and environmental management. The radiation process using electron beam is an ionization radiation process. Two facilities of electron accelerator have been established in pilot scale at the Centre for the Application of Isotope and Radiation CAIR-BATAN, Jakarta, for the RandD of radiation process technology and in demonstrating the electron accelerator application in industry in Indonesia. The first has low energy specification of 300 keV, 50 mA, EPS-300 type and the second has medium energy specification of 2 MeV, 10 mA dynamitron model GJ-2 type. Both the electron accelerators have an electron penetration depth capability of 0.6 and 12 mm, respectively, for the double side irradiation in the materials with density of 1 g/cm 3 . They also highly capacity production and electron beam cross-section of 120 cm length and 10 cm width. The beam will go through the atmosphere for irradiation samples or industrial products. The radiation dose can be selected precisely by adjusting the electron beam current and conveyor speed. Both of these facilities were applied in many aspects RandD, for examples dosimetry, wood surface coating, cross-linking of polymer, heatshrincable tube, polymer grafting, plastic degradation, food preservation, sterilization and so on. Engineering factors of radiation design process and general observation of electron accelerator application in RandD for various industries in Indonesia are briefly discussed

Social emotional consequences of accelerating gifted students

NARCIS (Netherlands)

Hoogeveen, A.J.M.

2008-01-01

This dissertations reports four studies on the social-emotional effects of accelerating gifted students. The research concentrated on how and to what extent educational programs, in interaction with environmental and personal factors, influence the functioning of gifted students, in the short and

The dynamics of fat, protein and sugar metabolism during walnut ...

African Journals Online (AJOL)

The result shows that the developmental process of walnut fruit could be divided into four stages: Slow growth {within 30 days after florescence, (DAF)}, fast growth (30 to 60 DAF), fat accumulation (60 to 100 DAF) and fruit maturity (100 to 140 DAF). Fat content in walnut fruit increased continuously and the maximum ...

Accelerations in Flight

Science.gov (United States)

Doolittle, J H

1925-01-01

This work on accelerometry was done at McCook Field for the purpose of continuing the work done by other investigators and obtaining the accelerations which occur when a high-speed pursuit airplane is subjected to the more common maneuvers. The accelerations obtained in suddenly pulling out of a dive with well-balanced elevators are shown to be within 3 or 4 per cent of the theoretically possible accelerations. The maximum acceleration which a pilot can withstand depends upon the length of time the acceleration is continued. It is shown that he experiences no difficulty under the instantaneous accelerations as high as 7.8 G., but when under accelerations in excess of 4.5 G., continued for several seconds, he quickly loses his faculties.

Theoretical Investigations of Plasma-Based Accelerators and Other Advanced Accelerator Concepts

International Nuclear Information System (INIS)

Shuets, G.

2004-01-01

Theoretical investigations of plasma-based accelerators and other advanced accelerator concepts. The focus of the work was on the development of plasma based and structure based accelerating concepts, including laser-plasma, plasma channel, and microwave driven plasma accelerators

Ultra-accelerated natural sunlight exposure testing

Science.gov (United States)

Jorgensen, Gary J.; Bingham, Carl; Goggin, Rita; Lewandowski, Allan A.; Netter, Judy C.

2000-06-13

Process and apparatus for providing ultra accelerated natural sunlight exposure testing of samples under controlled weathering without introducing unrealistic failure mechanisms in exposed materials and without breaking reciprocity relationships between flux exposure levels and cumulative dose that includes multiple concurrent levels of temperature and relative humidity at high levels of natural sunlight comprising: a) concentrating solar flux uniformly; b) directing the controlled uniform sunlight onto sample materials in a chamber enclosing multiple concurrent levels of temperature and relative humidity to allow the sample materials to be subjected to accelerated irradiance exposure factors for a sufficient period of time in days to provide a corresponding time of about at least a years worth of representative weathering of the sample materials.

Exchange bias in diluted-antiferromagnet/antiferromagnet bilayers

International Nuclear Information System (INIS)

Mao, Zhongquan; Zhan, Xiaozhi; Chen, Xi

2015-01-01

The hysteresis-loop properties of a diluted-antiferromagnetic (DAF) layer exchange coupling to an antiferromagnetic (AF) layer are investigated by means of numerical simulations. Remarkable loop shift and coercivity enhancement are observed in such DAF/AF bilayers, while they are absent in the uncoupled DAF single layer. The influences of pinned domains, dilution, cooling field and DAF layer thickness on the loop shift are investigated systematically. The result unambiguously confirms an exchange bias (EB) effect in the DAF/AF bilayers. It also reveals that the EB effect originates from the pinned AF domains within the DAF layer. In contrast to conventional EB systems, frozen uncompensated spins are not found at the interface of the AF pinning layer. (paper)

MOJAVE. XII. ACCELERATION AND COLLIMATION OF BLAZAR JETS ON PARSEC SCALES

Energy Technology Data Exchange (ETDEWEB)

Homan, D. C. [Department of Physics, Denison University, Granville, OH 43023 (United States); Lister, M. L.; Richards, J. L. [Department of Physics, Purdue University, 525 Northwestern Avenue, West Lafayette, IN 47907 (United States); Kovalev, Y. Y. [Astro Space Center of Lebedev Physical Institute, Profsoyuznaya 84/32, 117997 Moscow (Russian Federation); Pushkarev, A. B.; Savolainen, T.; Ros, E. [Max-Planck-Institut für Radioastronomie, Auf dem Hügel 69, D-53121 Bonn (Germany); Kellermann, K. I., E-mail: homand@denison.edu [National Radio Astronomy Observatory, 520 Edgemont Road, Charlottesville, VA 22903 (United States)

2015-01-10

We report on the acceleration properties of 329 features in 95 blazar jets from the MOJAVE Very Long Baseline Array program. Nearly half the features and three-quarters of the jets show significant changes in speed and/or direction. In general, apparent speed changes are distinctly larger than changes in direction, indicating that changes in the Lorentz factors of jet features dominate the observed speed changes rather than bends along the line of sight. Observed accelerations tend to increase the speed of features near the jet base, ≲ 10-20 pc projected, and decrease their speed at longer distances. The range of apparent speeds at a fixed distance in an individual jet can span a factor of a few, indicating that shock properties and geometry may influence the apparent motions; however, we suggest that the broad trend of jet features increasing their speed near the origin is due to an overall acceleration of the jet flow out to deprojected distances of the order of 10{sup 2} pc, beyond which the flow begins to decelerate or remains nearly constant in speed. We estimate intrinsic rates of change of the Lorentz factors in the galaxy frame of the order of Γ-dot /Γ≃10{sup −3} to 10{sup –2} yr{sup –1}, which can lead to total Lorentz factor changes of a factor of a few on the length scales observed here. Finally, we also find evidence for jet collimation at projected distances of ≲ 10 pc in the form of the non-radial motion and bending accelerations that tend to better align features with the inner jet.

Properties of the superconductor in accelerator dipole magnets

Science.gov (United States)

Teravest, Derk

Several aspects of the application of superconductors to high field dipole magnets for particle accelerators are discussed. The attention is focused on the 10 tesla (1 m model) magnet that is envisaged for the future Large Hadron Collider (LHC) accelerator. The basic motivation behind the study is the intention of employing superconductors to their utmost performance. An overview of practical supercomputers, their applications and their impact on high field dipole magnets used for particle accelerators, is presented. The LHC reference design for the dipole magnets is outlined. Several models were used to study the influence of a number of factors in the shape and in particular, the deviation from the shape that is due to the flux flow state. For the investigated extrinsic and intrinsic factors, a classification can be made with respect to the effect on the shape of the characteristic of a multifilamentary wire. The optimization of the coil structure for high field dipole magnets, with respect to the field quality is described. An analytical model for solid and hollow filaments, to calculate the effect of filament magnetization in the quality of the dipole field, is presented.

Large tandem accelerators

International Nuclear Information System (INIS)

Jones, C.M.

1976-01-01

The increasing importance of energetic heavy ion beams in the study of atomic physics, nuclear physics, and materials science has partially or wholly motivated the construction of a new generation of tandem accelerators designed to operate at maximum terminal potentials in the range 14 to 30 MV. In addition, a number of older tandem accelerators are now being significantly upgraded to improve their heavy ion performance. Both of these developments have reemphasized the importance of negative heavy ion sources. The new large tandem accelerators are described, and the requirements placed on negative heavy ion source technology by these and other tandem accelerators used for the acceleration of heavy ions are discussed. First, a brief description is given of the large tandem accelerators which have been completed recently, are under construction, or are funded for construction, second, the motivation for construction of these accelerators is discussed, and last, criteria for negative ion sources for use with these accelerators are presented

HARVEST TIME AND PHYSIOLOGIC QUALITY OF SEEDS IN IRRIGATED RICE (Oryza sativa cv. BRS RORAIMA ÉPOCA DE COLHEITA E QUALIDADE FISIOLÓGICA DE SEMENTES EM ARROZ IRRIGADO (Oryza sativa cv. BRS RORAIMA

Directory of Open Access Journals (Sweden)

Oscar José Smiderle

2008-09-01

Full Text Available

Harvest time is one of most important factors influencing rice seed characteristics for purpose of either planting or milling. With the objective to determine a proper harvesting  time, irrigated rice seeds of cultivar BRS Roraima were harvested at 15, 22, 29, 36, 43 and 50 days after flowering (DAF, and assessed according to humidity, viability, dry mass of 1,000 seeds, whole grain yield, productivity and storability. Seeds harvested 29 DAF showed high quality and its productivity was equivalent to the subsequent periods. Seeds harvested 50 DAF showed good performance, except for whole grain yield. Harvests 15 and 22 DAF were unsuitable, reducing the physiologic quality of seeds, mill efficiency and high initial humidity. The adequate harvest time for cultivar BRS Roraima is between 29 and 43 DAF, when seeds present higher yield, dry mass, whole grain yield, physiologic quality and storability.

KEY-WORDS: Physiologic quality; whole grain; humidity.

A época de colheita é um dos fatores mais importantes que influenciam as características da semente de arroz, seja para semeadura ou para consumo. Com o objetivo de determinar a época adequada de colheita de arroz irrigado, para a cultivar BRS Roraima, sementes foram colhidas aos 15, 22, 29, 36, 43 e 50 dias após o florescimento (DAF e avaliadas quanto à umidade, viabilidade, massa seca de 1.000 sementes, rendimento de grãos inteiros, produtividade e armazenabilidade. As sementes colhidas aos 29 DAF

A Statistical Perspective on Highly Accelerated Testing

Energy Technology Data Exchange (ETDEWEB)

Thomas, Edward V. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

2015-02-01

Highly accelerated life testing has been heavily promoted at Sandia (and elsewhere) as a means to rapidly identify product weaknesses caused by flaws in the product's design or manufacturing process. During product development, a small number of units are forced to fail at high stress. The failed units are then examined to determine the root causes of failure. The identification of the root causes of product failures exposed by highly accelerated life testing can instigate changes to the product's design and/or manufacturing process that result in a product with increased reliability. It is widely viewed that this qualitative use of highly accelerated life testing (often associated with the acronym HALT) can be useful. However, highly accelerated life testing has also been proposed as a quantitative means for "demonstrating" the reliability of a product where unreliability is associated with loss of margin via an identified and dominating failure mechanism. It is assumed that the dominant failure mechanism can be accelerated by changing the level of a stress factor that is assumed to be related to the dominant failure mode. In extreme cases, a minimal number of units (often from a pre-production lot) are subjected to a single highly accelerated stress relative to normal use. If no (or, sufficiently few) units fail at this high stress level, some might claim that a certain level of reliability has been demonstrated (relative to normal use conditions). Underlying this claim are assumptions regarding the level of knowledge associated with the relationship between the stress level and the probability of failure. The primary purpose of this document is to discuss (from a statistical perspective) the efficacy of using accelerated life testing protocols (and, in particular, "highly accelerated" protocols) to make quantitative inferences concerning the performance of a product (e.g., reliability) when in fact there is lack-of-knowledge and uncertainty concerning

Accelerator Availability and Reliability Issues

Energy Technology Data Exchange (ETDEWEB)

Steve Suhring

2003-05-01

Maintaining reliable machine operations for existing machines as well as planning for future machines' operability present significant challenges to those responsible for system performance and improvement. Changes to machine requirements and beam specifications often reduce overall machine availability in an effort to meet user needs. Accelerator reliability issues from around the world will be presented, followed by a discussion of the major factors influencing machine availability.

Plasma particle accelerators

International Nuclear Information System (INIS)

Dawson, J.M.

1988-01-01

The Superconducting Supercollider (SSC) will require an 87-kilometer accelerator ring to boost particles to 40 TeV. The SSC's size is due in part to the fact that its operating principle is the same one that has dominated accelerator design for 50 years: it guides particles by means of magnetic fields and propels them by strong electric fields. If one were to build an equally powerful but smaller accelerator, one would need to increase the strength of the guiding and propelling fields. Actually, however, conventional technology may not be able to provide significant increases in field strength. There are two reasons. First, the forces from magnetic fields are becoming greater than the structural forces that hold a magnetic material together; the magnets that produce these fields would themselves be torn apart. Second, the energy from electric fields is reaching the energies that bind electrons to atoms; it would tear electrons from nuclei in the accelerator's support structures. It is the electric field problem that plasma accelerators can overcome. Plasma particle accelerators are based on the principle that particles can be accelerated by the electric fields generated within a plasma. Because the plasma has already been ionized, plasma particle accelerators are not susceptible to electron dissociation. They can in theory sustain accelerating fields thousands of times stronger that conventional technologies. So far two methods for creating plasma waves for accelerators have been proposed and tested: the wakefield and the beat wave. Although promising electric fields have been produced, more research is necessary to determine whether plasma particle accelerators can compete with the existing accelerators. 7 figs

LU factorization for accelerator-based systems

KAUST Repository

Agullo, Emmanuel

2011-12-01

Multicore architectures enhanced with multiple GPUs are likely to become mainstream High Performance Computing (HPC) platforms in a near future. In this paper, we present the design and implementation of an LU factorization using tile algorithm that can fully exploit the potential of such platforms in spite of their complexity. We use a methodology derived from previous work on Cholesky and QR factorizations. Our contributions essentially consist of providing new CPU/GPU hybrid LU kernels, studying the impact on performance of the looking variants as well as the storage layout in presence of pivoting, tuning the kernels for two different machines composed of multiple recent NVIDIA Tesla S1070 (four GPUs total) and Fermi-based S2050 GPUs (three GPUs total), respectively. The hybrid tile LU asymptotically achieves 1 Tflop/s in single precision on both hardwares. The performance in double precision arithmetic reaches 500 Gflop/s on the Fermi-based system, twice faster than the old GPU generation of Tesla S1070. We also discuss the impact of the number of tiles on the numerical stability. We show that the numerical results of the tile LU factorization will be accurate enough for most applications as long as the computations are performed in double precision arithmetic. © 2011 IEEE.

Molecular ion acceleration using tandem accelerator

Energy Technology Data Exchange (ETDEWEB)

Saito, Yuichi; Mizuhashi, Kiyoshi; Tajima, Satoshi [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment

1996-12-01

In TIARA compound beam radiation system, cluster beams have been produced using 3 MV tandem accelerator (9SDH-2) to supply them to various radiation on injection experiments. Till now, productions of C{sub 2-8}, Si{sub 2-4} and O{sub 2} and their accelerations up to 6 MeV have been succeeded. This study aimed at production and acceleration of B{sub 2-4} and LiF. Anion clusters were produced using the conventional ion source of cesium sputter type. The proportions of atoms, molecules and clusters elicited from the ion source were varied depending on the material`s properties and the operating conditions of ion source such as sample temperature, sputter voltage and the shape of sample. The anion clusters were accelerated toward the high voltage terminal in the center of tandem accelerator, leading to cations through losing their electrons by the collision to N{sub 2} gas in a charge conversion cell at the terminal. Positively charged cluster ions could be obtained by modulating the pressure of N{sub 2} gas. Thus, B{sub 2} (64 nA), B{sub 3} (4.4 nA) and B{sub 4} (2.7 nA) have been produced and their maximum survival probabilities were higher than those of carbon or silicon clusters. In addition, the relationship between beam current and gas pressure was investigated for Bn (n = 2-4) and LiF. (M.N.)

TeV/m Nano-Accelerator: Current Status of CNT-Channeling Acceleration Experiment

Energy Technology Data Exchange (ETDEWEB)

Shin, Young Min [Northern Illinois U.; Lumpkin, Alex H. [Fermilab; Thangaraj, Jayakar Charles [Fermilab; Thurman-Keup, Randy Michael [Fermilab; Shiltsev, Vladimir D. [Fermilab

2014-09-17

Crystal channeling technology has offered various opportunities in the accelerator community with a viability of ultrahigh gradient (TV/m) acceleration for future HEP collider. The major challenge of channeling acceleration is that ultimate acceleration gradients might require a high power driver in the hard x-ray regime (~ 40 keV). This x-ray energy exceeds those for x-rays as of today, although x-ray lasers can efficiently excite solid plasma and accelerate particles inside a crystal channel. Moreover, only disposable crystal accelerators are possible at such high externally excited fields which would exceed the ionization thresholds destroying the atomic structure, so acceleration will take place only in a short time before full dissociation of the lattice. Carbon-based nanostructures have great potential with a wide range of flexibility and superior physical strength, which can be applied to channeling acceleration. This paper presents a beam- driven channeling acceleration concept with CNTs and discusses feasible experiments with the Advanced Superconducting Test Accelerator (ASTA) in Fermilab.

Design studies of heavy ion linear accelerators constructed of independently phased spiral resonators

International Nuclear Information System (INIS)

Stokes, R.H.; Armstrong, D.D.

1975-01-01

Preliminary design studies are reported for two linear accelerators for heavy ions. One accelerator is a high-intensity machine which would operate with 100 percent duty factor and would produce tin ions with 6.1 MeV/A. Alternatively, it could be operated under pulsed conditions with 25 percent duty factor and would then accelerate uranium ions to 8.1 MeV/A, tin ions to 10.5 MeV/A, and all lighter ions to higher velocities. It would be injected with a positive multicharge ion source and a 4-MV single-ended dc generator. Also, design studies are reported for small postaccelerator injected by a model FN tandem. Both accelerators use three-drift-tube spiral resonators operating at room temperature. Magnetic quadrupole singlets are placed between all resonators to provide radial focussing. Each resonator is independently phased according to the velocity of the ion to be accelerated. The ability to adjust the phase of each resonator permits variations in final energy and other beam properties with great flexibility. (U.S.)