Piracy of Decay-Accelerating Factor (CD55) Signal Transduction by the Diffusely Adhering Strain Escherichia coli C1845 Promotes Cytoskeletal F-Actin Rearrangements in Cultured Human Intestinal INT407 Cells

PubMed Central

Peiffer, Isabelle; Servin, Alain L.; Bernet-Camard, Marie-Françoise

1998-01-01

Diffusely adhering Escherichia coli (DAEC) C1845 (clinical isolate) harboring the fimbrial adhesin F1845 can infect cultured human differentiated intestinal epithelial cells; this process is followed by the disassembly of the actin network in the apical domain. The aim of this study was to examine the mechanism by which DAEC C1845 promotes F-actin rearrangements. For this purpose, we used a human embryonic intestinal cell line (INT407) expressing the membrane-associated glycosylphosphatidylinositol (GPI) protein-anchored decay-accelerating factor (DAF), the receptor of the F1845 adhesin. We show here that infection of INT407 cells by DAEC C1845 can provoke dramatic F-actin rearrangements without cell entry. Clustering of phosphotyrosines was observed, revealing that the DAEC C1845-DAF interaction involves the recruitment of signal transduction molecules. A pharmacological approach with a subset of inhibitors of signal transduction molecules was used to identify the cascade of signal transduction molecules that are coupled to the DAF, that are activated upon infection, and that promote the F-actin rearrangements. DAEC C1845-induced F-actin rearrangements can be blocked dose dependently by protein tyrosine kinase, phospholipase Cγ, phosphatidylinositol 3-kinase, protein kinase C, and Ca2+ inhibitors. F-actin rearrangements and blocking by inhibitors were observed after infection of the cells with two E. coli recombinants carrying the plasmids containing the fimbrial adhesin F1845 or the fimbrial hemagglutinin Dr, belonging to the same family of adhesins. These findings show that the DAEC Dr family of pathogens promotes alterations in the intestinal cell cytoskeleton by piracy of the DAF-GPI signal cascade without bacterial cell entry. PMID:9712744

Coupling complement regulators to immunoglobulin domains generates effective anti-complement reagents with extended half-life in vivo

PubMed Central

HARRIS, C L; WILLIAMS, A S; LINTON, S M; MORGAN, B P

2002-01-01

Complement activation and subsequent generation of inflammatory molecules and membrane attack complex contributes to the pathology of a number of inflammatory and degenerative diseases, including arthritis, glomerulonephritis and demyelination. Agents that specifically inhibit complement activation might prove beneficial in the treatment of these diseases. Soluble recombinant forms of the naturally occurring membrane complement regulatory proteins (CRP) have been exploited for this purpose. We have undertaken to design better therapeutics based on CRP. Here we describe the generation of soluble, recombinant CRP comprising rat decay accelerating factor (DAF) or rat CD59 expressed as Fc fusion proteins, antibody-like molecules comprising two CRP moieties in place of the antibody Fab arms (CRP-Ig). Reagents bearing DAF on each arm (DAF-Ig), CD59 on each arm (CD59-Ig) and a hybrid reagent containing both DAF and CD59 were generated. All three reagents inhibited C activation in vitro. Compared with soluble CRP lacking Fc domains, activity was reduced, but was fully restored by enzymatic release of the regulator from the Ig moiety, implicating steric constraints in reducing functional activity. In vivo studies showed that DAF-Ig, when compared to soluble DAF, had a much extended half-life in the circulation in rats and concomitantly caused a sustained reduction in plasma complement activity. When given intra-articularly to rats in a model of arthritis, DAF-Ig significantly reduced severity of disease. The data demonstrate the potential of CRP-Ig as reagents for sustained therapy of inflammatory disorders, including arthritis, but emphasize the need for careful design of fusion proteins to retain function. PMID:12165074

Release of complement regulatory proteins from ocular surface cells in infections.

PubMed

Cocuzzi, E; Guidubaldi, J; Bardenstein, D S; Chen, R; Jacobs, M R; Medof, E M

2000-11-01

The decay accelerating factor (DAF or CD55) and the membrane inhibitor of reactive lysis (MIRL or CD59), two complement regulatory proteins that protect self cells from autologous complement-mediated injury, are attached to corneal and cqonjunctival epithelial cells by glycosylphos-phatidylinositol (GPI) anchors. We sought to 1) determine the frequency with which bacteria recovered from patients with infections of the eye elaborate factors that can remove these surface proteins from ocular cells, 2) determine the spectrum of bacteria from other sites that have similar effects, and 3) establish the time interval required for reconstitution of the two regulators. Culture supernatants of 18 ocular isolates [P. aeruginosa (n = 3), S. marcescens (n = 1), S. epidermidis (n = 9), and S. aureus (n = 5)], and > 100 other clinical specimens isolated in the hospital's microbiology laboratory [P. mirabilis (n = 1), S. aureus (n = 65), S. epidermidis (n = 24), B. cereus (n = 12), H. influenzae (n = 15), and Enterobacter sp. (n = 21)] were incubated at 37 degrees C for various times with conjunctival epithelial cells, conjunctival fibroblasts or HeLa cells and the release of DAF and CD59 proteins from the surfaces of the cells analyzed by 2-site immunoradiometric assays and by Western blotting. The kinetics of recovery of DAF and CD59 expression on the cells was measured by flow cytometry. DAF and/or CD59 release from the cell monolayers varied from < 5% to > 99% at as much as a 1:81 dilution of the supernatant from some bacteria. On conjunctival epithelial cells, more than 8 hr was required for 44% recovery of DAF expression and for 50% recovery of CD59 expression. Bacteria produce phospholipases and/or other enzymes which can efficiently remove DAF and CD59 from ocular cell surfaces. This phenomenon may correlate with their in vivo pathogenicity.

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

PubMed

Gelmedin, Verena; Brodigan, Thomas; Gao, Xin; Krause, Michael; Wang, Zhu; Hawdon, John M

2011-01-01

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.

Absence of Gal epitope prolongs survival of swine lungs in an ex vivo model of hyperacute rejection

PubMed Central

Nguyen, Bao-Ngoc H.; Azimzadeh, Agnes M.; Schroeder, Carsten; Buddensick, Thomas; Zhang, Tianshu; Laaris, Amal; Cochrane, Megan; Schuurman, Henk-Jan; Sachs, David H.; Allan, James S.; Pierson, Richard N.

2012-01-01

Background Galactosyl transferase gene knock-out (GalTKO) swine offer a unique tool to evaluate the role of the Gal antigen in xenogenic lung hyperacute rejection. Methods We perfused GalTKO miniature swine lungs with human blood. Results were compared with those from previous studies using wild-type and human decay-accelerating factor-transgenic (hDAF+/+) pig lungs. Results GalTKO lungs survived 132 ± 52 min compared to 10 ± 9 min for wild-type lungs (P = 0.001) and 45 ± 60 min for hDAF+/+ lungs (P = 0.18). GalTKO lungs displayed stable physiologic flow and pulmonary vascular resistance (PVR) until shortly before graft demise, similar to autologous perfusion, and unlike wild-type or hDAF+/+ lungs. Early (15 and 60 min) complement (C3a) and platelet activation and intrapulmonary platelet deposition were significantly diminished in GalTKO lungs relative to wild-type or hDAF+/+ lungs. However, GalTKO lungs adsorbed cytotoxic anti-non-Gal antibody and elaborated high levels of thrombin; their demise was associated with increased PVR, capillary congestion, intravascular thrombi and strong CD41 deposition not seen at earlier time points. Conclusions In summary, GalTKO lungs are substantially protected from injury but, in addition to anti-non-Gal antibody and complement, platelet adhesion and non-physiologic intravascular coagulation contribute to Gal-independent lung injury mechanisms. PMID:21496117

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

PubMed

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.

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

PubMed

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.

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

PubMed Central

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

2013-01-01

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 Ca2+/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 PMID:23805378

Augmentation of Antitumor T-Cell Responses by Increasing APC T-Cell C5a/C3a-C5aR/C3aR Interactions

DTIC Science & Technology

2013-03-01

the surface of cells after incorporation of decay-accelerating factor (DAF) into their membranes. The Journal of experimental medicine . 1984;160(5...cell immunity. The Journal of experimental medicine . 2005;201(10):1523-30. PubMed PMID: 15883171. 3. Vogel CW, Wilkie SD, Morgan AC. In vivo studies...with covalent conjugates of cobra venom factor and monoclonal antibodies to human tumors. Haematology and blood transfusion. 1985;29:514- 7. Epub

Analysis of the signal for attachment of a glycophospholipid membrane anchor

PubMed Central

1989-01-01

The COOH terminus of decay accelerating factor (DAF) contains a signal that directs attachment of a glycophospholipid (GPI) membrane anchor. To define this signal we deleted portions of the DAF COOH terminus and expressed the mutant cDNAs it CV1 origin-deficient SV-40 cells. Our results show that the COOH-terminal hydrophobic domain (17 residues) is absolutely required for GPI anchor attachment. However, when fused to the COOH terminus of a secreted protein this hydrophobic domain is insufficient to direct attachment of a GPI anchor. Additional specific information located within the adjacent 20 residues appears to be necessary. We speculate that by analogy with signal sequences for membrane translocation, GPI anchor attachment requires both a COOH- terminal hydrophobic domain (the GPI signal) as well as a suitable cleavage/attachment site located NH2 terminal to the signal. PMID:2466848

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

PubMed

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 that daf-16/FOXO promotes developmental arrest cell-nonautonomously by repressing pathways that promote larval development.

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

PubMed Central

Moore, Brad T.; Jordan, James M.; Maxwell, Colin S.; Schindler, Adam J.; Baugh, L. Ryan

2015-01-01

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 that daf-16/FOXO promotes developmental arrest cell-nonautonomously by repressing pathways that promote larval development. PMID:26656736

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

PubMed Central

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

SUMMARY One of the major determinants of aging in organisms ranging from worms to man are FOXO family transcription factors, which are downstream effectors of Insulin/IGF-1 signaling (IIS). 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. PMID:26154057

Insulin/IGF1 Signaling Inhibits Age-Dependent Axon Regeneration

PubMed Central

Byrne, Alexandra B.; Walradt, Trent; Gardner, Kathryn E.; Hubbert, Austin; Reinke, Valerie; Hammarlund, Marc

2014-01-01

Summary The ability of injured axons to regenerate declines with age yet the mechanisms that regulate axon regeneration in response to age are not known. Here we show that axon regeneration in aging C. elegans motor neurons is inhibited by the conserved insulin/IGF1 receptor DAF-2. DAF-2’s function in regeneration is mediated by intrinsic neuronal activity of the forkhead transcription factor DAF-16/FOXO. DAF-16 regulates regeneration independently of lifespan, indicating that neuronal aging is an intrinsic, neuron specific, and genetically regulated process. In addition, we found that daf-18/PTEN inhibits regeneration independently of age and FOXO signaling, via the TOR pathway. Finally, DLK-1, a conserved regulator of regeneration, is downregulated by insulin/IGF1 signaling, bound by DAF-16 in neurons, and is required for both DAF-16- and DAF-18-mediated regeneration. Together, our data establish that insulin signaling specifically inhibits regeneration in aging adult neurons, and that this mechanism is independent of PTEN and TOR. PMID:24440228

daf-16: An HNF-3/forkhead family member that can function to double the life-span of Caenorhabditis elegans.

PubMed

Lin, K; Dorman, J B; Rodan, A; Kenyon, C

1997-11-14

The wild-type Caenorhabditis elegans nematode ages rapidly, undergoing development, senescence, and death in less than 3 weeks. In contrast, mutants with reduced activity of the gene daf-2, a homolog of the insulin and insulin-like growth factor receptors, age more slowly than normal and live more than twice as long. These mutants are active and fully fertile and have normal metabolic rates. The life-span extension caused by daf-2 mutations requires the activity of the gene daf-16. daf-16 appears to play a unique role in life-span regulation and encodes a member of the hepatocyte nuclear factor 3 (HNF-3)/forkhead family of transcriptional regulators. In humans, insulin down-regulates the expression of certain genes by antagonizing the activity of HNF-3, raising the possibility that aspects of this regulatory system have been conserved.

Refolding of soluble leukemia inhibitory factor receptor fusion protein (gp 190 sol DAF) from urea.

PubMed

Liu, H; Moreau, J F; Gualde, N; Fu, J

1997-04-01

The insoluble inclusion bodies of soluble leukemia inhibitory factor receptor fusion protein (gp 190 sol DAF) was solubilized in 8 M urea on the unfolding transitions, and several factors on the aggregate formation were indirectly analyzed for the refolding of gp 190 sol DAF. Results indicate that the refolding yield can be considerably increased at lowering concentration of the unfolding protein, a little soluble protein with the slow refolding appears in the process of the aggregate formation and the concentration of the denaturant must be down to a minimum level for its refolding.

Comparisons of Four Methods for Estimating a Dynamic Factor Model

ERIC Educational Resources Information Center

Zhang, Zhiyong; Hamaker, Ellen L.; Nesselroade, John R.

2008-01-01

Four methods for estimating a dynamic factor model, the direct autoregressive factor score (DAFS) model, are evaluated and compared. The first method estimates the DAFS model using a Kalman filter algorithm based on its state space model representation. The second one employs the maximum likelihood estimation method based on the construction of a…

Noncanonical control of C. elegans germline apoptosis by the insulin/IGF-1 and Ras/MAPK signaling pathways.

PubMed

Perrin, A J; Gunda, M; Yu, B; Yen, K; Ito, S; Forster, S; Tissenbaum, H A; Derry, W B

2013-01-01

The insulin/IGF-1 pathway controls a number of physiological processes in the nematode worm Caenorhabditis elegans, including development, aging and stress response. We previously found that the Akt/PKB ortholog AKT-1 dampens the apoptotic response to genotoxic stress in the germline by negatively regulating the p53-like transcription factor CEP-1. Here, we report unexpected rearrangements to the insulin/IGF-1 pathway, whereby the insulin-like receptor DAF-2 and 3-phosphoinositide-dependent protein kinase PDK-1 oppose AKT-1 to promote DNA damage-induced apoptosis. While DNA damage does not affect phosphorylation at the PDK-1 site Thr350/Thr308 of AKT-1, it increased phosphorylation at Ser517/Ser473. Although ablation of daf-2 or pdk-1 completely suppressed akt-1-dependent apoptosis, the transcriptional activation of CEP-1 was unaffected, suggesting that daf-2 and pdk-1 act independently or downstream of cep-1 and akt-1. Ablation of the akt-1 paralog akt-2 or the downstream target of the insulin/IGF-1 pathway daf-16 (a FOXO transcription factor) restored sensitivity to damage-induced apoptosis in daf-2 and pdk-1 mutants. In addition, daf-2 and pdk-1 mutants have reduced levels of phospho-MPK-1/ERK in their germ cells, indicating that the insulin/IGF-1 pathway promotes Ras signaling in the germline. Ablation of the Ras effector gla-3, a negative regulator of mpk-1, restored sensitivity to apoptosis in daf-2 mutants, suggesting that gla-3 acts downstream of daf-2. In addition, the hypersensitivity of let-60/Ras gain-of-function mutants to damage-induced apoptosis was suppressed to wild-type levels by ablation of daf-2. Thus, insulin/IGF-1 signaling selectively engages AKT-2/DAF-16 to promote DNA damage-induced germ cell apoptosis downstream of CEP-1 through the Ras pathway.

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.

PubMed

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.

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

PubMed Central

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

2014-01-01

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. PMID:25330323

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

PubMed

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-2/Hc-DAF-2 in the biology and development of H. contortus, particularly in the transition to parasitism. Copyright © 2014 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Immunogenicity of HILDA/LIF either in a soluble or in a membrane anchored form expressed in vivo by recombinant vaccinia viruses.

PubMed

Taupin, J L; Acres, B; Dott, K; Schmitt, D; Kieny, M P; Gualde, N; Moreau, J F

1993-09-01

Insertion of various cDNAs in the genome of the vaccinia virus (VV) enables the in vivo and in vitro study of the functional role and/or the immunogenicity of the virally encoded recombinant proteins. We have prepared a recombinant VV expressing the cDNA of the human cytokine HILDA/LIF (human interleukin for DA cells/leukaemia inhibitory factor), and used this virus to immunize mice against this protein, which is very homologous to its murine counterpart (approximately 80% homology). We also constructed and expressed by the same system a chimeric gene encoding the HILDA/LIF protein fused to the 37 COOH-terminal amino-acids of the human decay accelerating factor (DAF). This sequence proved to be sufficient for the targeting of the fusion protein to the cell membrane, where it is linked to the phosphatidylinositols. Both recombinant VVs induced cytokine-specific antibodies in mice as analysed with an ELISA where the recombinant HILDA/LIF was plastic-coated and a cytofluorometric assay where the LIF-DAF molecule was present at the cell surface of stably transfected P815. In the latter case HILDA/LIF remained biologically active suggesting that it was expressed in its native form. The LIF-DAF fusion protein was found to exhibit a better capacity to elicit an antibody response against the native form of the cytokine as detected in cytofluorometric assays. Whatever the recombinant virus used to immunize the mice, the MoAbs obtained were positive either in the ELISA or in the cytofluorometric assays but one, which suggested that the plastic coating induced a conformational change of HILDA/LIF.

[Using delayed auditory feedback in the treatment of stuttering: evidence to consider].

PubMed

Van Borsel, John; Sierens, Sarah; Pereira, Mônica Medeiros de Britto

2007-01-01

There is some indication that the use of delayed auditory feedback (DAF) is a potentially helpful technique in the treatment of stuttering. Several devices for DAF are also commercially. However, not all individuals who stutter experience a positive effect on speech fluency when speaking under DAF. And those who do show a positive effect, may differ considerably as to the degree and the conditions in which the effect is seen. Therefore, the decision whether or not to attempt the use of DAF in an given client is usually not straightforward. Starting from a literature review, the present paper discusses and illustrates factors to take into account when considering the use of RAA in an individual client. Four types of factors are distinguished: factors inherent to the client such as gender, age, stuttering severity, dysfluency pattern, origin of stuttering, and biological subtype; factors outside the client including delay time, intensity, manner of delivery, speech mode, and speech situation; possible side-effects like a reduction in speech rate, an increase of speaking fundamental frequency and vocal intensity, lengthening of vowels, and a possible effect on speech naturalness; others namely cosmetics, finances, and the long-term effect. The review shows that most likely multiple factors play a role, but with the currently available data it is very hard to predict whether a given individual will or will not benefit from the use of DAF. Overall, the evidence for the influence of the different factors is still meager. Moreover, some studies present data of a quality that can hardly be considered "evidence".

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

NASA Astrophysics Data System (ADS)

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.

Gravity Force Transduced by the MEC-4/MEC-10 DEG/ENaC Channel Modulates DAF-16/FoxO Activity in Caenorhabditis elegans

PubMed Central

Kim, Nahui; Dempsey, Catherine M.; Kuan, Chih-Jen; Zoval, Jim V.; O'Rourke, Eyleen; Ruvkun, Gary; Madou, Marc J.; Sze, Ji Y.

2007-01-01

The gravity response is an array of behavioral and physiological plasticity elicited by changes in ambient mechanical force and is an evolutionarily ancient adaptive mechanism. We show in Caenorhabditis elegans that the force of hypergravity is translated into biological signaling via a genetic pathway involving three factors: the degenerin/epithelial Na+ channel (DEG/ENaC) class of mechanosensory channels of touch receptor neurons, the neurotransmitter serotonin, and the FoxO transcription factor DAF-16 known to regulate development, energy metabolism, stress responses, and aging. After worms were exposed to hypergravity for 3 hr, their muscular and neuronal functions were preserved, but they exhibited DAF-16∷GFP nuclear accumulation in cells throughout the body and accumulated excess fat. Mutations in MEC-4/MEC-10 DEG/ENaC or its partners MEC-6, MEC-7, and MEC-9 blocked DAF-16∷GFP nuclear accumulation induced by hypergravity but did not affect DAF-16 response to other stresses. We show that exogenous serotonin and the antidepressant fluoxetine can attenuate DAF-16∷GFP nuclear accumulation in WT animals exposed to hypergravity. These results reveal a novel physiological role of the mechanosensory channel, showing that the perception of mechanical stress controls FoxO signaling pathways and that inactivation of DEG/ENaC may decouple mechanical loading and physiological responses. PMID:17720915

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

PubMed Central

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

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.

PubMed

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.

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

PubMed

Jensen, Victor L; Simonsen, Karina T; Lee, Yu-Hui; Park, Donha; Riddle, Donald L

2010-12-31

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.

Oat consumption reduced intestinal fat deposition and improved health span in Caenorhabditis elegans model

PubMed Central

Gao, Chenfei; Gao, Zhanguo; Greenway, Frank L.; Burton, Jeffrey H.; Johnson, William D.; Keenan, Michael J.; Enright, Frederick M.; Martin, Roy J.; Chu, YiFang; Zheng, Jolene

2015-01-01

In addition to their fermentable dietary fiber and the soluble β-glucan fiber, oats have unique avenanthramides that have anti-inflammatory and antioxidant properties that reduce coronary heart disease in human clinical trials. We hypothesized that oat consumption will increase insulin sensitivity, reduce body fat, and improve health span in Caenorhabditis elegans through a mechanism involving the daf-2 gene, which codes for the insulin/insulin-like growth factor-1–like receptor, and that hyperglycemia will attenuate these changes. Caenorhabditis elegans wild type (N2) and the null strains sir-2.1, daf-16, and daf-16/daf-2 were fed Escherichia coli (OP50) and oat flakes (0.5%, 1.0%, or 3%) with and without 2% glucose. Oat feeding decreased intestinal fat deposition in N2, daf-16, or daf-16/daf-2 strains (P < .05); and glucose did not affect intestinal fat deposition response. The N2, daf-16, or sir-2.1 mutant increased the pharyngeal pumping rate (P < .05), a surrogate marker of life span, following oat consumption. Oat consumption increased ckr-1, gcy-8, cpt-1, and cpt-2 mRNA expression in both the N2 and the sir-2.1 mutant, with significantly higher expression in sir-2.1 than in N2 (P < .01). Additional glucose further increased expression 1.5-fold of the 4 genes in N2 (P < .01), decreased the expression of all except cpt-1 in the daf-16 mutant, and reduced mRNA expression of the 4 genes in the daf-16/daf-2 mutant (P < .01). These data suggest that oat consumption reduced fat storage and increased ckr-1, gcy-8, cpt-1, or cpt-2 through the sir-2.1 genetic pathway. Oat consumption may be a beneficial dietary intervention for reducing fat accumulation, augmenting health span, and improving hyperglycemia-impaired lipid metabolism. PMID:26253816

Unexpected role for dosage compensation in the control of dauer arrest, insulin-like signaling, and FoxO transcription factor activity in Caenorhabditis elegans.

PubMed

Dumas, Kathleen J; Delaney, Colin E; Flibotte, Stephane; Moerman, Donald G; Csankovszki, Gyorgyi; Hu, Patrick J

2013-07-01

During embryogenesis, an essential process known as dosage compensation is initiated to equalize gene expression from sex chromosomes. Although much is known about how dosage compensation is established, the consequences of modulating the stability of dosage compensation postembryonically are not known. Here we define a role for the Caenorhabditis elegans dosage compensation complex (DCC) in the regulation of DAF-2 insulin-like signaling. In a screen for dauer regulatory genes that control the activity of the FoxO transcription factor DAF-16, we isolated three mutant alleles of dpy-21, which encodes a conserved DCC component. Knockdown of multiple DCC components in hermaphrodite and male animals indicates that the dauer suppression phenotype of dpy-21 mutants is due to a defect in dosage compensation per se. In dpy-21 mutants, expression of several X-linked genes that promote dauer bypass is elevated, including four genes encoding components of the DAF-2 insulin-like pathway that antagonize DAF-16/FoxO activity. Accordingly, dpy-21 mutation reduced the expression of DAF-16/FoxO target genes by promoting the exclusion of DAF-16/FoxO from nuclei. Thus, dosage compensation enhances dauer arrest by repressing X-linked genes that promote reproductive development through the inhibition of DAF-16/FoxO nuclear translocation. This work is the first to establish a specific postembryonic function for dosage compensation in any organism. The influence of dosage compensation on dauer arrest, a larval developmental fate governed by the integration of multiple environmental inputs and signaling outputs, suggests that the dosage compensation machinery may respond to external cues by modulating signaling pathways through chromosome-wide regulation of gene expression.

C. elegans EAK-3 inhibits dauer arrest via nonautonomous regulation of nuclear DAF-16/FoxO activity

PubMed Central

Zhang, Yanmei; Xu, Jinling; Puscau, Cristina; Kim, Yongsoon; Wang, Xi; Alam, Hena; Hu, Patrick J.

2008-01-01

SUMMARY Insulin regulates development, metabolism, and lifespan via a conserved PI3K/Akt pathway that promotes cytoplasmic sequestration of FoxO transcription factors. The regulation of nuclear FoxO is poorly understood. In the nematode Caenorhabditis elegans, insulin-like signaling functions in larvae to inhibit dauer arrest and acts during adulthood to regulate lifespan. In a screen for genes that modulate C. elegans insulin-like signaling, we identified eak-3, which encodes a novel protein that is specifically expressed in the two endocrine XXX cells. The dauer arrest phenotype of eak-3 mutants is fully suppressed by mutations in daf-16/FoxO, which encodes the major target of C. elegans insulin-like signaling, and daf-12, which encodes a nuclear receptor regulated by steroid hormones known as dafachronic acids. eak-3 mutation does not affect DAF-16/FoxO subcellular localization but enhances expression of the direct DAF-16/FoxO target sod-3 in a daf-16/FoxO- and daf-12-dependent manner. eak-3 mutants have normal lifespans, suggesting that EAK-3 decouples insulin-like regulation of development and longevity. We propose that EAK-3 activity in the XXX cells promotes the synthesis and/or secretion of a hormone that acts in parallel to AKT-1 to inhibit the expression of DAF-16/FoxO target genes. Similar hormonal pathways may regulate FoxO target gene expression in mammals. PMID:18241854

Differential insertion of GPI-anchored GFPs into lipid rafts of live cells.

PubMed

Legler, Daniel F; Doucey, Marie-Agnès; Schneider, Pascal; Chapatte, Laurence; Bender, Florent C; Bron, Claude

2005-01-01

Partitioning of proteins in cholesterol and sphingolipid enriched plasma membrane microdomains, called lipid rafts, is critical for many signal transduction and protein sorting events. Although raft partitioning of many signaling molecules remains to be determined, glycosylphosphatidyl-inositol (GPI)-anchored proteins possess high affinity for lipid rafts and are currently exploited as markers to investigate fundamental mechanisms in protein sorting and signal transduction events. In this study, we demonstrate that two recombinant GPI-anchored green fluorescent proteins (GFP-GPIs) that differ in their GPI signal sequence confer distinct localization in plasma membrane microdomains. GFP fused to the GPI signal of the decay accelerating factor GFP-GPI(DAF) partitioned exclusively in lipid rafts, whereas GFP fused to the GPI signal of TRAIL-R3, GFP-GPI(TRAIL-R3), associated only minimally with microdomains. In addition, we investigated the unique ability of purified GFP-GPIs to insert into membrane microdomains of primary lymphocytes. This cell surface painting allows rapid, stable, and functional association of the GPI-anchored proteins with the target cell plasma membrane. The distinct membrane localization of the two GFP-GPIs was observed irrespective of whether the GPI-anchored molecules were painted or transfected. Furthermore, we show that painted GFP-GPI(DAF) was totally dependent on the GPI anchor and that the membrane insertion was increased by the addition of raft-associated lipids such as cholesterol, sphingomyelin, and dipalmitoyl-phosphatidylethanolamine. Thus, this study provides evidence that different GPI signal sequences lead to distinct membrane microdomain localization and that painted GFP-GPI(DAF) serves as an excellent fluorescent marker for lipid rafts in live cells.

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

NASA Astrophysics Data System (ADS)

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).

Redox regulation, gene expression and longevity.

PubMed

Honda, Yoko; Tanaka, Masashi; Honda, Shuji

2010-07-01

Lifespan can be lengthened by genetic and environmental modifications. Study of these might provide valuable insights into the mechanism of aging. Low doses of radiation and short-term exposure to heat and high concentrations of oxygen prolong the lifespan of the nematode Caenorhabditis elegans. These might be caused by adaptive responses to harmful environmental conditions. Single-gene mutations have been found to extend lifespan in C. elegans, Drosophila and mice. So far, the best-characterized system is the C. elegans mutant in the daf-2, insulin/IGF-I receptor gene that is the component of the insulin/IGF-I signaling pathway. The mutant animals live twice as long as the wild type. The insulin/IGF-I signaling pathway regulates the activity of DAF-16, a FOXO transcription factor. However, the unified explanation for the function of DAF-16 transcription targets in the lifespan extension is not yet fully established. As both of the Mn superoxide dismutase (MnSOD) isoforms (sod-2 and sod-3) are found to be targets of DAF-16, we attempted to assess their functions in regulating lifespan and oxidative stress responsivity. We show that the double deletions of sod-2 and sod-3 genes induced oxidative-stress sensitivity but do not shorten lifespan in the daf-2 mutant background, indicating that oxidative stress is not necessarily a limiting factor for longevity. Furthermore, the deletion in the sod-3 gene lengthens lifespan in the daf-2 mutant. We conclude that the MnSOD systems in C. elegans fine-tune the insulin/IGF-I-signaling based regulation of longevity by acting not as anti-oxidants but as physiological-redox-signaling modulators.

Homologous species restriction of the complement-mediated killing of nucleated cells.

PubMed Central

Yamamoto, H; Blaas, P; Nicholson-Weller, A; Hänsch, G M

1990-01-01

The homologous restriction of complement (C) lysis is attributed to membrane proteins: decay-accelerating factor (DAF), C8 binding protein (C8bp) and P18/CD59. Since these proteins are also expressed on peripheral blood cells, species restriction was tested for in the complement-mediated killing of antibody-coated human leucocytes by human or rabbit complement. Killing was more efficient when rabbit complement was used. Preincubation of cells with an antibody to DAF abolished the difference. When C1-7 sites were first attached to the cells and either rabbit or human C8, C9 were added, the killing of monocytes and lymphocytes was equally efficient; only in polymorphonuclear neutrophils was a higher efficiency of rabbit C8, C9 seen. Thus, in contrast to haemolysis, restriction occurred predominantly at the C3 level and the action of the terminal complement components was not inhibited. Since C8bp isolated from peripheral blood cells showed essentially similar characteristics as the erythrocyte-derived C8bp, the failure of C8bp to inhibit the action of the terminal components on nucleated cells might reflect differences of the complement membrane interactions between erythrocytes or nucleated cells, respectively. Images Figure 5 PMID:1697561

Pristionchus pacificus daf-16 is essential for dauer formation but dispensable for mouth form dimorphism.

PubMed

Ogawa, Akira; Bento, Gilberto; Bartelmes, Gabi; Dieterich, Christoph; Sommer, Ralf J

2011-04-01

The nematode Pristionchus pacificus shows two forms of phenotypic plasticity: dauer formation and dimorphism of mouth form morphologies. It can therefore serve as a model for studying the evolutionary mechanisms that underlie phenotypic plasticity. Formation of dauer larvae is observed in many other species and constitutes one of the most crucial survival strategies in nematodes, whereas the mouth form dimorphism is an evolutionary novelty observed only in P. pacificus and related nematodes. We have previously shown that the same environmental cues and steroid signaling control both dauer formation and mouth form dimorphism. Here, we examine by mutational analysis and whole-genome sequencing the function of P. pacificus (Ppa) daf-16, which encodes a forkhead transcription factor; in C. elegans, daf-16 is the target of insulin signaling and plays important roles in dauer formation. We found that mutations in Ppa-daf-16 cause strong dauer formation-defective phenotypes, suggesting that Ppa-daf-16 represents one of the evolutionarily conserved regulators of dauer formation. Upon strong dauer induction with lophenol, Ppa-daf-16 individuals formed arrested larvae that partially resemble wild-type dauer larvae, indicating that Ppa-daf-16 is also required for dauer morphogenesis. By contrast, regulation of mouth form dimorphism was unaffected by Ppa-daf-16 mutations and mutant animals responded normally to environmental cues. Our results suggest that mechanisms for dauer formation and mouth form regulation overlap partially, but not completely, and one of two key transcriptional regulators of the dauer regulatory network was either independently co-opted for, or subsequently lost by, the mouth form regulatory network.

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

PubMed

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.

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

PubMed Central

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

2015-01-01

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. PMID:26620638

Transcriptional targets of DAF-16 insulin signaling pathway protect C. elegans from extreme hypertonic stress.

PubMed

Lamitina, S Todd; Strange, Kevin

2005-02-01

All cells adapt to hypertonic stress by regulating their volume after shrinkage, by accumulating organic osmolytes, and by activating mechanisms that protect against and repair hypertonicity-induced damage. In mammals and nematodes, inhibition of signaling from the DAF-2/IGF-1 insulin receptor activates the DAF-16/FOXO transcription factor, resulting in increased life span and resistance to some types of stress. We tested the hypothesis that inhibition of insulin signaling in Caenorhabditis elegans also increases hypertonic stress resistance. Genetic inhibition of DAF-2 or its downstream target, the AGE-1 phosphatidylinositol 3-kinase, confers striking resistance to a normally lethal hypertonic shock in a DAF-16-dependent manner. However, insulin signaling is not inhibited by or required for adaptation to hypertonic conditions. Microarray studies have identified 263 genes that are transcriptionally upregulated by DAF-16 activation. We identified 14 DAF-16-upregulated genes by RNA interference screening that are required for age-1 hypertonic stress resistance. These genes encode heat shock proteins, proteins of unknown function, and trehalose synthesis enzymes. Trehalose levels were elevated approximately twofold in age-1 mutants, but this increase was insufficient to prevent rapid hypertonic shrinkage. However, age-1 animals unable to synthesize trehalose survive poorly under hypertonic conditions. We conclude that increased expression of proteins that protect eukaryotic cells against environmental stress and/or repair stress-induced molecular damage confers hypertonic stress resistance in C. elegans daf-2/age-1 mutants. Elevated levels of solutes such as trehalose may also function in a cytoprotective manner. Our studies provide novel insights into stress resistance in animal cells and a foundation for new studies aimed at defining molecular mechanisms underlying these essential processes.

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

PubMed

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.

Neuronal Migration Is Regulated by Endogenous RNAi and Chromatin-Binding Factor ZFP-1/AF10 in Caenorhabditis elegans

PubMed Central

Kennedy, Lisa M.; Grishok, Alla

2014-01-01

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. PMID:24558261

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

PubMed

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 Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Genes that regulate both development and longevity in Caenorhabditis elegans

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

Larsen, P.L.; Albert, P.S.; Riddle, D.L.

1995-04-01

The nematode Caenorhabditis elegans responds to conditions of overcrowding and limited food by arresting development as a dauer larva. Genetic analysis of mutations that alter dauer larva formation (daf mutations) is presented along with an updated genetic pathway for dauer vs. nondauer development. Mutations in the daf-2 and daf-23 genes double adult life span, whereas mutations in four other dauer-constitutive genes positioned in a separate branch of this pathway (daf-1, daf-4, daf-7 and daf-8) do not. The increased life spans are suppressed completely by a daf-16 mutation and partially in a daf-2; daf-18 double mutant. A genetic pathway for determinationmore » of adult life span is presented based on the same strains and growth conditions used to characterize Daf phenotypes. Both dauer larva formation and adult life span are affected in daf-2; daf-12 double mutants in an allele-specific manner. Mutations in daf-12 do not extend adult life span, but certain combinations of daf-2 and daf-12 mutant alleles nearly quadruple it. This synergistic effect, which does not equivalently extend the fertile period, is the largest genetic extension of life span yet observed in a metazoan. 47 refs., 7 figs., 5 tabs.« less

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

PubMed

Gaglia, Marta M; Jeong, Dae-Eun; Ryu, Eun-A; Lee, Dongyeop; Kenyon, Cynthia; Lee, Seung-Jae

2012-01-01

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.

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

PubMed Central

2011-01-01

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. PMID:21749693

Cloning of the transgenic pigs expressing human decay accelerating factor and N-acetylglucosaminyltransferase III.

PubMed

Fujimura, Tatsuya; Kurome, Mayuko; Murakami, Hiroshi; Takahagi, Yoichi; Matsunami, Katsuyoshi; Shimanuki, Shinichi; Suzuki, Kohei; Miyagawa, Shuji; Shirakura, Ryota; Shigehisa, Tamotsu; Nagashima, Hiroshi

2004-01-01

The present paper describes production of cloned pigs from fibroblast cells of transgenic pigs expressing human decay accelerating factor (DAF, CD55) and N-acetylglucosaminyltransferase III (GnT-III) that remodels sugar-chain biosynthesis. Two nuclear transfer protocols were used: a two-step activation (TA) method and a delayed activation (DA) method. Enucleated in vitro-matured oocytes and donor cells were electrically fused in a calcium-containing medium by TA method or in a calcium-free medium by DA method, followed by electrical activation 1-1.5 h later, respectively. In vitro blastocyst formation rates of nuclear transferred embryos reconstructed by TA and DA method were 8% and 14%, respectively. As a result of embryo transfer of the reconstructed embryos made by each method into recipient pigs, both gave rise to cloned piglets. These cloned pigs expressed transgene as much as their nuclear donor cells. In conclusions, (1) pig cloning can be carried out by TA or DA nuclear transfer methods, (2) expression of transgenes can be maintained to cloned pigs from the nuclear donor cells derived from transgenic animals.

Complement in Lupus Nephritis: New Perspectives.

PubMed

Bao, Lihua; Cunningham, Patrick N; Quigg, Richard J

2015-09-01

Systemic lupus erythematosus (SLE) is an autoimmune disorder caused by loss of tolerance to self-antigens, the production of autoantibodies and deposition of complement-fixing immune complexes (ICs) in injured tissues. SLE is characterized by a wide range of clinical manifestations and targeted organs, with lupus nephritis being one of the most serious complications. The complement system consists of three pathways and is tightly controlled by a set of regulatory proteins to prevent injudicious complement activation on host tissue. The involvement of the complement system in the pathogenesis of SLE is well accepted; yet, its exact role is still not clear. Complement plays dual roles in the pathogenesis of SLE. On the one hand, the complement system appears to have protective features in that hereditary homozygous deficiencies of classical pathway components, such as C1q and C4, are associated with an increased risk for SLE. On the other hand, IC-mediated activation of complement in affected tissues is clearly evident in both experimental and human SLE along with pathological features that are logical consequences of complement activation. Studies in genetically altered mice have shown that lack of complement inhibitors, such as complement factor H (CFH) or decay-accelerating factor (DAF) accelerates the development of experimental lupus nephritis, while treatment with recombinant protein inhibitors, such as Crry-Ig, CR2-Crry, CR2-DAF and CR2-CFH, ameliorates the disease development. Complement-targeted drugs, including soluble complement receptor 1 (TP10), C1 esterase inhibitor and a monoclonal anti-C5 antibody (eculizumab), have been shown to inhibit complement safely, and are now being investigated in a variety of clinical conditions. SLE is an autoimmune disorder which targets multiple systems. Complement is centrally involved and plays dual roles in the pathogenesis of SLE. Studies from experimental lupus models and clinical trials support the use of complement-targeted therapy in the treatment of SLE.

Oscillographic and Physiological Measurements of Delayed Auditory Feedback and Anxiety Factors in Stutterers and Non-Stutterers.

ERIC Educational Resources Information Center

Timmons, Beverly A.; Boudreau, James P.

Reported are five studies on the use of delayed auditory feedback (DAF) with stutterers. The first study indicates that sex differences and age differences in temporal reaction were found when subjects (5-, 7-, 9-, 11-, and 13-years-old) recited a nursery rhyme under DAF and NAF (normal auditory feedback) conditions. The second study is reported…

The age-1 and daf-2 genes function in a common pathway to control the lifespan of Caenorhabditis elegans.

PubMed

Dorman, J B; Albinder, B; Shroyer, T; Kenyon, C

1995-12-01

Recessive mutations in two genes, daf-2 and age-1, extend the lifespan of Caenorhabditis elegans significantly. The daf-2 gene also regulates formation of an alternative developmental state called the dauer. Here we asked whether these two genes function in the same or different lifespan pathways. We found that the longevity of both age-1 and daf-2 mutants requires the activities of the same two genes, daf-16 and daf-18. In addition, the daf-2(e1370); age-1(hx546) double mutant did not live significantly longer than the daf-2 single mutant. We also found that, like daf-2 mutations, the age-1(hx546) mutation affects certain aspects of dauer formation. These findings suggest that age-1 and daf-2 mutations do act in the same lifespan pathway and extend lifespan by triggering similar if not identical processes.

The Age-1 and Daf-2 Genes Function in a Common Pathway to Control the Lifespan of Caenorhabditis Elegans

PubMed Central

Dorman, J. B.; Albinder, B.; Shroyer, T.; Kenyon, C.

1995-01-01

Recessive mutations in two genes, daf-2 and age-1, extend the lifespan of Caenorhabditis elegans significantly. The daf-2 gene also regulates formation of an alternative developmental state called the dauer. Here we asked whether these two genes function in the same or different lifespan pathways. We found that the longevity of both age-1 and daf-2 mutants requires the activities of the same two genes, daf-16 and daf-18. In addition, the daf-2(e1370); age-1(hx546) double mutant did not live significantly longer than the daf-2 single mutant. We also found that, like daf-2 mutations, the age-1(hx546) mutation affects certain aspects of dauer formation. These findings suggest that age-1 and daf-2 mutations do act in the same lifespan pathway and extend lifespan by triggering similar if not identical processes. PMID:8601482

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

PubMed

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.

Identification of Direct Target Genes Using Joint Sequence and Expression Likelihood with Application to DAF-16

PubMed Central

Yu, Ron X.; Liu, Jie; True, Nick; Wang, Wei

2008-01-01

A major challenge in the post-genome era is to reconstruct regulatory networks from the biological knowledge accumulated up to date. The development of tools for identifying direct target genes of transcription factors (TFs) is critical to this endeavor. Given a set of microarray experiments, a probabilistic model called TRANSMODIS has been developed which can infer the direct targets of a TF by integrating sequence motif, gene expression and ChIP-chip data. The performance of TRANSMODIS was first validated on a set of transcription factor perturbation experiments (TFPEs) involving Pho4p, a well studied TF in Saccharomyces cerevisiae. TRANSMODIS removed elements of arbitrariness in manual target gene selection process and produced results that concur with one's intuition. TRANSMODIS was further validated on a genome-wide scale by comparing it with two other methods in Saccharomyces cerevisiae. The usefulness of TRANSMODIS was then demonstrated by applying it to the identification of direct targets of DAF-16, a critical TF regulating ageing in Caenorhabditis elegans. We found that 189 genes were tightly regulated by DAF-16. In addition, DAF-16 has differential preference for motifs when acting as an activator or repressor, which awaits experimental verification. TRANSMODIS is computationally efficient and robust, making it a useful probabilistic framework for finding immediate targets. PMID:18350157

No Significant Increase in the Δ4- and Δ7-Dafachronic Acid Concentration in the Long-Lived glp-1 Mutant, nor in the Mutants Defective in Dauer Formation.

PubMed

Li, Tie-Mei; Liu, Weilong; Lu, Shan; Zhang, Yan-Ping; Jia, Le-Mei; Chen, Jie; Li, Xiangke; Lei, Xiaoguang; Dong, Meng-Qiu

2015-05-12

The steroid hormone dafachronic acid (DA) regulates dauer formation and lifespan in Caenorhabditis elegans by binding to the nuclear receptor DAF-12. However, little is known about how DA concentrations change under various physiologic conditions and about how DA/DAF-12 signaling interacts with other signaling pathways that also regulate dauer formation and lifespan. Using a sensitive bioanalytical method, we quantified the endogenous DA concentrations in a long-lived germline-less glp-1 mutant and in the Dauer formation-defective (Daf-d) mutants daf-12, daf-16, daf-5, and daf-3. We found that the DA concentration in the glp-1 mutant was similar to that in the wild type (WT). This result is contrary to the long-held belief that germline loss-induced longevity involves increased DA production and suggests instead that this type of longevity involves an enhanced response to DA. We also found evidence suggesting that increased DA sensitivity underlies lifespan extension triggered by exogenous DA. At the L2/L3 stage, the DA concentration in a daf-12 null mutant decreased to 22% of the WT level. This finding is consistent with the previously proposed positive feedback regulation between DAF-12 and DA production. Surprisingly, the DA concentrations in the daf-16, daf-5, and daf-3 mutants were only 19-34% of the WT level at the L2/L3 stage, slightly greater than those in the Dauer formation-constitutive (Daf-c) mutants at the pre-dauer stage (4-15% of the WT L2 control). Our experimental evidence suggested that the positive feedback between DA and DAF-12 was partially induced in the three Daf-d mutants. Copyright © 2015 Li et al.

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

PubMed Central

Büchter, Christian; Ackermann, Daniela; Havermann, Susannah; Honnen, Sebastian; Chovolou, Yvonni; Fritz, Gerhard; Kampkötter, Andreas; Wätjen, Wim

2013-01-01

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. PMID:23736695

Molecular Basis for Antioxidant Enzymes in Mediating Copper Detoxification in the Nematode Caenorhabditis elegans

PubMed Central

Song, Shaojuan; Zhang, Xueyao; Wu, Haihua; Han, Yan; Zhang, Jianzhen; Ma, Enbo; Guo, Yaping

2014-01-01

Antioxidant enzymes play a major role in defending against oxidative damage by copper. However, few studies have been performed to determine which antioxidant enzymes respond to and are necessary for copper detoxification. In this study, we examined both the activities and mRNA levels of SOD, CAT, and GPX under excessive copper stress in Caenorhabditis elegans, which is a powerful model for toxicity studies. Then, taking advantage of the genetics of this model, we assessed the lethal concentration (LC50) values of copper for related mutant strains. The results showed that the SOD, CAT, and GPX activities were significantly greater in treated groups than in controls. The mRNA levels of sod-3, sod-5, ctl-1, ctl-2, and almost all gpx genes were also significantly greater in treated groups than in controls. Among tested mutants, the sod-5, ctl-1, gpx-3, gpx-4, and gpx-6 variants exhibited hypersensitivity to copper. The strains with SOD or CAT over expression were reduced sensitive to copper. Mutations in daf-2 and age-1, which are involved in the insulin/insulin-like growth factor-1 signaling pathway, result in reduced sensitivity to stress. Here, we showed that LC50 values for copper in daf-2 and age-1 mutants were significantly greater than in N2 worms. However, the LC50 values in daf-16;daf-2 and daf-16;age-1 mutants were significantly reduced than in daf-2 and age-1 mutants, implying that reduced copper sensitivity is influenced by DAF-16-related functioning. SOD, CAT, and GPX activities and the mRNA levels of the associated copper responsive genes were significantly increased in daf-2 and age-1 mutants compared to N2. Additionally, the activities of SOD, CAT, and GPX were greater in these mutants than in N2 when treated with copper. Our results not only support the theory that antioxidant enzymes play an important role in copper detoxification but also identify the response and the genes involved in these processes. PMID:25243607

Deep Sequencing-guided Design of a High Affinity Dual Specificity Antibody to Target Two Angiogenic Factors in Neovascular Age-related Macular Degeneration* ♦

PubMed Central

Koenig, Patrick; Lee, Chingwei V.; Sanowar, Sarah; Wu, Ping; Stinson, Jeremy; Harris, Seth F.; Fuh, Germaine

2015-01-01

The development of dual targeting antibodies promises therapies with improved efficacy over mono-specific antibodies. Here, we engineered a Two-in-One VEGF/angiopoietin 2 antibody with dual action Fab (DAF) as a potential therapeutic for neovascular age-related macular degeneration. Crystal structures of the VEGF/angiopoietin 2 DAF in complex with its two antigens showed highly overlapping binding sites. To achieve sufficient affinity of the DAF to block both angiogenic factors, we turned to deep mutational scanning in the complementarity determining regions (CDRs). By mutating all three CDRs of each antibody chain simultaneously, we were able not only to identify affinity improving single mutations but also mutation pairs from different CDRs that synergistically improve both binding functions. Furthermore, insights into the cooperativity between mutations allowed us to identify fold-stabilizing mutations in the CDRs. The data obtained from deep mutational scanning reveal that the majority of the 52 CDR residues are utilized differently for the two antigen binding function and permit, for the first time, the engineering of several DAF variants with sub-nanomolar affinity against two structurally unrelated antigens. The improved variants show similar blocking activity of receptor binding as the high affinity mono-specific antibodies against these two proteins, demonstrating the feasibility of generating a dual specificity binding surface with comparable properties to individual high affinity mono-specific antibodies. PMID:26088137

Alternate metabolism during the dauer stage of the nematode Caenorhabditis elegans.

PubMed

Burnell, Ann M; Houthoofd, Koen; O'Hanlon, Karen; Vanfleteren, Jacques R

2005-11-01

When environmental conditions are unsuitable to support nematode reproduction, Caenorhabditis elegans arrests development before the onset of sexual maturity and specialised 'dauer' larvae, adapted for dispersal, and extended diapause are formed. Dauer larvae do not feed and their metabolism is dependent on internal food reserves. Adult worms which express defects in the insulin/insulin-like growth factor receptor DAF-2 also display enhanced longevity. Whole genome mRNA expression profiling has demonstrated that C. elegans dauer larvae and daf-2 adults have similar transcription profiles for a cohort of longevity genes. Important components of this enhanced longevity system are the alpha-crystallin family of small heat shock proteins, anti-ROS defence systems, increased activity of cellular detoxification processes and possibly also increased chromatin stability and decreased protein turnover. Anaerobic fermentation pathways are upregulated in dauer larvae, while long-lived daf-2 adults appear to have normal oxidative metabolism. Anabolic pathways are down regulated in dauer larvae (and possibly in daf-2 adults as well), and energy consumption appears to be diverted to enhanced cellular maintenance and detoxification processes in both systems.

A MicroRNA-Mediated Insulin Signaling Pathway Regulates the Toxicity of Multi-Walled Carbon Nanotubes in Nematode Caenorhabditis elegans

NASA Astrophysics Data System (ADS)

Zhao, Yunli; Yang, Junnian; Wang, Dayong

2016-03-01

The underlying mechanisms for functions of microRNAs (miRNAs) in regulating toxicity of nanomaterials are largely unclear. Using Illumina HiSeqTM 2000 sequencing technique, we obtained the dysregulated mRNA profiling in multi-walled carbon nanotubes (MWCNTs) exposed nematodes. Some dysregulated genes encode insulin signaling pathway. Genetic experiments confirmed the functions of these dysregulated genes in regulating MWCNTs toxicity. In the insulin signaling pathway, DAF-2/insulin receptor regulated MWCNTs toxicity by suppressing function of DAF-16/FOXO transcription factor. Moreover, we raised a miRNAs-mRNAs network involved in the control of MWCNTs toxicity. In this network, mir-355 might regulate MWCNTs toxicity by inhibiting functions of its targeted gene of daf-2, suggesting that mir-355 may regulate functions of the entire insulin signaling pathway by acting as an upregulator of DAF-2, the initiator of insulin signaling pathway, in MWCNTs exposed nematodes. Our results provides highlight on understanding the crucial role of miRNAs in regulating toxicity of nanomaterials in organisms.

Gender by assertiveness interaction in delayed auditory feedback.

PubMed

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.

A MicroRNA-Mediated Insulin Signaling Pathway Regulates the Toxicity of Multi-Walled Carbon Nanotubes in Nematode Caenorhabditis elegans

PubMed Central

Zhao, Yunli; Yang, Junnian; Wang, Dayong

2016-01-01

The underlying mechanisms for functions of microRNAs (miRNAs) in regulating toxicity of nanomaterials are largely unclear. Using Illumina HiSeqTM 2000 sequencing technique, we obtained the dysregulated mRNA profiling in multi-walled carbon nanotubes (MWCNTs) exposed nematodes. Some dysregulated genes encode insulin signaling pathway. Genetic experiments confirmed the functions of these dysregulated genes in regulating MWCNTs toxicity. In the insulin signaling pathway, DAF-2/insulin receptor regulated MWCNTs toxicity by suppressing function of DAF-16/FOXO transcription factor. Moreover, we raised a miRNAs-mRNAs network involved in the control of MWCNTs toxicity. In this network, mir-355 might regulate MWCNTs toxicity by inhibiting functions of its targeted gene of daf-2, suggesting that mir-355 may regulate functions of the entire insulin signaling pathway by acting as an upregulator of DAF-2, the initiator of insulin signaling pathway, in MWCNTs exposed nematodes. Our results provides highlight on understanding the crucial role of miRNAs in regulating toxicity of nanomaterials in organisms. PMID:26984256

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

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

Du, Yijun; Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan; Pattnaik, Asit K.

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 thatmore » 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.« less

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

PubMed Central

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

Insulin/Insulin-like growth factor signaling controls non-Dauer developmental speed in the nematode Caenorhabditis elegans.

PubMed

Ruaud, Anne-Françoise; Katic, Iskra; Bessereau, Jean-Louis

2011-01-01

Identified as a major pathway controlling entry in the facultative dauer diapause stage, the DAF-2/Insulin receptor (InsR) signaling acts in multiple developmental and physiological regulation events in Caenorhabditis elegans. Here we identified a role of the insulin-like pathway in controlling developmental speed during the C. elegans second larval stage. This role relies on the canonical DAF-16/FOXO-dependent branch of the insulin-like signaling and is largely independent of dauer formation. Our studies provide further evidence for broad conservation of insulin/insulin-like growth factor (IGF) functions in developmental speed control.

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

PubMed

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.

The Thioredoxin TRX-1 Modulates the Function of the Insulin-Like Neuropeptide DAF-28 during Dauer Formation in Caenorhabditis elegans

PubMed Central

Fierro-González, Juan Carlos; Cornils, Astrid; Alcedo, Joy

2011-01-01

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. PMID:21304598

Breeding new seedless grape by means of in vitro embryo rescue.

PubMed

Ji, W; Li, Z-Q; Zhou, Q; Yao, W-K; Wang, Y-J

2013-03-26

This project aimed at breeding new seedless grape cultivars by embryo rescue through three hybridization methods: 1) using cross-breeding between seedless Vitis vinifera cultivars and wild Chinese Vitis spp; 2) crossing with two seedless cultivars, and 3) hybridization between grapes of different ploidy. Genotype, sampling times, and media were confirmed to play important roles in this system. Among the different genotypes, the productions of hybrid plants were significantly different, ranging from 23.0% (Ruby Seedless x Black Olympia) to only 1.1% (Pink Seedless x Beichun), except for the combinations from which no surviving seedlings were obtained. We got the best sampling times, in days after flowering (DAF), from the following different combinations: 'Flame Seedless x Beichun' (39 DAF); 'Blush Seedless x Shuangyou' (54 DAF); 'Pink Seedless x Beichun' (54 DAF); 'DA7 x Shuangyou' (44 DAF); 'Blush Seedless x Thompson Seedless (54 DAF)'; 'Pink Seedless x Flame Seedless' (54 DAF); 'DA7 x Blush Seedless' (44 DAF); 'Ruby Seedless x Black Olympia' (63 DAF); 'DA7 x Jingyou' (44 DAF); 'Flame Seedless x Fujiminori' (39 DAF), and 'Big Black x Kyoho' (72 DAF). The highest rates of embryo formation (13.2%) and plant development (90.1%) were found when ovules were cultured in MM4 with 500 mg/L mashed banana. Conversely, they were reduced by addition of plant growth regulators. Seven new hybrids were successfully obtained. As a result of early nuclear-free character and ploidy level identification, 11 seedless grape lines, and 3 triploid and 2 haploid grape lines were obtained.

Pig kidney transplantation in baboons: anti-Gal(alpha)1-3Gal IgM alone is associated with acute humoral xenograft rejection and disseminated intravascular coagulation.

PubMed

Bühler, L; Yamada, K; Kitamura, H; Alwayn, I P; Basker, M; Appel, J Z; Colvin, R B; White-Scharf, M E; Sachs, D H; Robson, S C; Awwad, M; Cooper, D K

2001-12-15

Kidneys harvested from miniature swine or pigs transgenic for human decay-accelerating factor (hDAF) were transplanted into baboons receiving an anti-CD154 monoclonal antibody (mAb) and either a whole body irradiation (WBI)- or cyclophosphamide (CPP)-based immunosuppressive regimen. Group 1 baboons (n=3) underwent induction therapy with WBI and thymic irradiation, pretransplantation antithymocyte globulin, and immunoadsorption of anti-Gal(alpha)1-3Gal (Gal) antibody (Ab). After transplantation of a miniature swine kidney, maintenance therapy comprised cobra venom factor, mycophenolate mofetil, and an anti-CD154 mAb (for 14-28 days). In group 2 (n=2), WBI was replaced by CPP in the induction protocol. Group 3 (n=3) animals received the group 2 regimen, but underwent transplantation with hDAF pig kidneys. Group 1 and 2 animals developed features of disseminated intravascular coagulation (DIC), with reductions of fibrinogen and platelets and increases of prothrombin time, partial thromboplastin time, and fibrin split products. Graft survival was for 6-13 days. Histology showed mild acute humoral xenograft rejection (AHXR) of the kidneys, but severe rejection of the ureters. Group 3 animals developed features of DIC in two of three cases during the fourth week, with AHXR in the third case. Graft survival was for 28 (n=1) or 29 (n=2) days. Histology of day 15 biopsy specimens showed minimal focal mononuclear cellular infiltrates, with predominantly CD3+ cells. By days 28 and 29, kidneys showed mild-to-moderate features of AHXR. In all groups, the humoral response was manifest by reappearance of anti-Gal IgM below baseline level, with no or low return of anti-Gal IgG. All excised kidneys showed IgM deposition, but no complement and no or minimal IgG deposition. No baboon showed a rebound of anti-Gal Ab immediately after excision of the graft, and anti-Gal Ab increased over pretransplantation levels only when anti-CD154 mAb was discontinued. DIC was observed with WBI- or CPP-based therapy, and after miniature swine or hDAF kidney transplantation. AHXR+/-DIC was observed in all recipients even in the absence of complement and no or low levels of anti-Gal IgG, but was significantly delayed in the hDAF recipients. These results confirm our earlier observation that CD154 blockade prevents T cell-dependent sensitization in baboons to pig antigens, but that baseline natural anti-Gal Ab production is not inhibited. We suggest that IgM deposition, even in the absence of IgG and complement, leads to endothelial cell activation with the development of DIC, even when there are only minimal histologic changes of AHXR.

Effects of a Caenorhabditis elegans dauer pheromone ascaroside on physiology and signal transduction pathways.

PubMed

Gallo, Marco; Riddle, Donald L

2009-02-01

Daumone is one of the three purified and artificially synthesized components of the Caenorhabditis elegans dauer pheromone. It affects the major signal transduction pathways known to discriminate between developmental arrest at the dauer stage and growth to the adult [the transforming growth factor beta (TGF-beta) and daf-2/IGF1R pathways], just as natural pheromone extracts do. Transcription of daf-7/TGF-beta is reduced in pre-dauer larvae, and nuclear localization of the DAF-16/FOXO transcription factor is increased in embryos and L1 larvae exposed to synthetic daumone. However, daumone does not require the cilia in the amphidial neurons to produce these effects nor does it require the Galpha protein GPA-3 to induce dauer entry, although GPA-3 is required for dauer induction by natural dauer pheromone extracts. Synthetic daumone has physiological effects that have not been observed with natural pheromone. It is toxic at the concentrations required for bioassay and is lethal to mutants with defective cuticles. The molecular and physiological effects of daumone and natural dauer pheromone are only partially overlapping.

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

PubMed

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.

Deep Sequencing-guided Design of a High Affinity Dual Specificity Antibody to Target Two Angiogenic Factors in Neovascular Age-related Macular Degeneration.

PubMed

Koenig, Patrick; Lee, Chingwei V; Sanowar, Sarah; Wu, Ping; Stinson, Jeremy; Harris, Seth F; Fuh, Germaine

2015-09-04

The development of dual targeting antibodies promises therapies with improved efficacy over mono-specific antibodies. Here, we engineered a Two-in-One VEGF/angiopoietin 2 antibody with dual action Fab (DAF) as a potential therapeutic for neovascular age-related macular degeneration. Crystal structures of the VEGF/angiopoietin 2 DAF in complex with its two antigens showed highly overlapping binding sites. To achieve sufficient affinity of the DAF to block both angiogenic factors, we turned to deep mutational scanning in the complementarity determining regions (CDRs). By mutating all three CDRs of each antibody chain simultaneously, we were able not only to identify affinity improving single mutations but also mutation pairs from different CDRs that synergistically improve both binding functions. Furthermore, insights into the cooperativity between mutations allowed us to identify fold-stabilizing mutations in the CDRs. The data obtained from deep mutational scanning reveal that the majority of the 52 CDR residues are utilized differently for the two antigen binding function and permit, for the first time, the engineering of several DAF variants with sub-nanomolar affinity against two structurally unrelated antigens. The improved variants show similar blocking activity of receptor binding as the high affinity mono-specific antibodies against these two proteins, demonstrating the feasibility of generating a dual specificity binding surface with comparable properties to individual high affinity mono-specific antibodies. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Aspirin increases metabolism through germline signalling to extend the lifespan of Caenorhabditis elegans

PubMed Central

Huang, Xiao-Bing; Mu, Xiao-Hui; Wan, Qin-Li; He, Xiao-Ming; Wu, Gui-Sheng

2017-01-01

Aspirin is a prototypic cyclooxygenase inhibitor with a variety of beneficial effects on human health. It prevents age-related diseases and delays the aging process. Previous research has shown that aspirin might act through a dietary restriction-like mechanism to extend lifespan. To explore the mechanism of action of aspirin on aging, we determined the whole-genome expression profile of Caenorhabditis elegans treated with aspirin. Transcriptome analysis revealed the RNA levels of genes involved in metabolism were primarily increased. Reproduction has been reported to be associated with metabolism. We found that aspirin did not extend the lifespan or improve the heat stress resistance of germline mutants of glp-1. Furthermore, Oil Red O staining showed that aspirin treatment decreased lipid deposition and increased expression of lipid hydrolysis and fatty acid β-oxidation-related genes. The effect of germline ablation on lifespan was mainly mediated by DAF-12 and DAF-16. Next, we performed genetic analysis with a series of worm mutants and found that aspirin did not further extend the lifespans of daf-12 and daf-16 single mutants, glp-1;daf-12 and glp-1;daf-16 double mutants, or glp-1;daf-12;daf-16 triple mutants. The results suggest that aspirin increase metabolism and regulate germline signalling to activate downstream DAF-12 and DAF-16 to extend lifespan. PMID:28910305

Role of superoxide–nitric oxide interactions in the accelerated age-related loss of muscle mass in mice lacking Cu,Zn superoxide dismutase

PubMed Central

Sakellariou, Giorgos K; Pye, Deborah; Vasilaki, Aphrodite; Zibrik, Lea; Palomero, Jesus; Kabayo, Tabitha; McArdle, Francis; Van Remmen, Holly; Richardson, Arlan; Tidball, James G; McArdle, Anne; Jackson, Malcolm J

2011-01-01

Summary Mice lacking Cu,Zn superoxide dismutase (SOD1) show accelerated, age-related loss of muscle mass. Lack of SOD1 may lead to increased superoxide, reduced nitric oxide (NO), and increased peroxynitrite, each of which could initiate muscle fiber loss. Single muscle fibers from flexor digitorum brevis of wild-type (WT) and Sod1−/− mice were loaded with NO-sensitive (4-amino-5-methylamino-2′,7′-difluorofluorescein diacetate, DAF-FM) and superoxide-sensitive (dihydroethidium, DHE) probes. Gastrocnemius muscles were analyzed for SOD enzymes, nitric oxide synthases (NOS), and 3-nitrotyrosine (3-NT) content. A lack of SOD1 did not increase superoxide availability at rest because no increase in ethidium or 2-hydroxyethidium (2-HE) formation from DHE was seen in fibers from Sod1−/− mice compared with those from WT mice. Fibers from Sod1−/− mice had decreased NO availability (decreased DAF-FM fluorescence), increased 3-NT in muscle proteins indicating increased peroxynitrite formation and increased content of peroxiredoxin V (a peroxynitrite reductase), compared with WT mice. Muscle fibers from Sod1−/− mice showed substantially reduced generation of superoxide in response to contractions compared with fibers from WT mice. Inhibition of NOS did not affect DHE oxidation in fibers from WT or Sod1−/− mice at rest or during contractions, but transgenic mice overexpressing nNOS showed increased DAF-FM fluorescence and reduced DHE oxidation in resting muscle fibers. It is concluded that formation of peroxynitrite in muscle fibers is a major effect of lack of SOD1 in Sod1−/− mice and may contribute to fiber loss in this model, and that NO regulates superoxide availability and peroxynitrite formation in muscle. PMID:21443684

FOXO3a is broadly neuroprotective in vitro and in vivo against insults implicated in motor neuron diseases

PubMed Central

Mojsilovic-Petrovic, Jelena; Nedelsky, Natalia; Boccitto, Marco; Mano, Itzhak; Georgiades, Savvas N.; Zhou, Weiguo; Liu, Yuhong; Neve, Rachael L.; Taylor, J. Paul; Driscoll, Monica; Clardy, Jon; Merry, Diane; Kalb, Robert G.

2009-01-01

Aging is a risk factor for the development of adult-onset neuro-degenerative diseases. While some of the molecular pathways regulating longevity and stress resistance in lower organisms are defined (i.e., those activating the transcriptional regulators DAF-16 and HSF-1 in C. elegans), their relevance to mammals and disease susceptibility are unknown. We studied the signaling controlled by the mammalian homolog of DAF-16, FOXO3a, in model systems of motor neuron disease. Neuron death elicited in vitro by excitotoxic insult or the expression of mutant SOD1, mutant p150glued or polyQ expanded androgen receptor was abrogated by expression of nuclear-targeted FOXO3a. We identify a compound (Psammaplysene A, PA) that increases nuclear localization of FOXO3a in vitro and in vivo and show that PA also protects against these insults in vitro. Administration of PA to invertebrate model systems of neurodegeneration similarly blocked neuron death in a DAF-16/FOXO3a-dependent manner. These results indicate that activation of the DAF-16/FOXO3a pathway, genetically or pharmacologically, confers protection against the known causes of motor neuron diseases. PMID:19553463

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

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

Depuydt, Geert G.; Xie, Fang; Petyuk, Vladislav A.

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 intermediarymore » 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.« less

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

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

Depuydt, Geert; Xie, Fang; Petyuk, Vladislav A.

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 intermediarymore » 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.« less

Pilot testing of dissolved air flotation (DAF) in a highly effective coagulation-flocculation integrated (FRD) system.

PubMed

Wang, Yili; Guo, Jinlong; Tang, Hongxiao

2002-01-01

Factors of pretreatment coagulation/flocculation units were studied using raw water of low temperature and low turbidity. Aluminum sulfate (AS) and selected polyaluminium chlorides (PACls) were all effective in the DAF process when used under favorable conditions of coagulant addition, coagulation, flocculation and flotation units. Compared with the AS coagulant, PACls, at lower dosage, could give the same effective performance even with shorter coagulation/flocculation time or lower recycle ratio during the treatment of cold water. This is attributed to the higher-charged polymeric Al species, and the lower hydrophilic and more compact flocculated flocs of PACl coagulant. Based on results of pilot experiments, the goal of FRD system can be achieved by combining a DAF heterocoagulation reactor with PACl coagulant (F), an efficient flocculation reactor (R), as well as an economical auto-dosing system (D).

Clustering of Genetically Defined Allele Classes in the Caenorhabditis elegans DAF-2 Insulin/IGF-1 Receptor

PubMed Central

Patel, Dhaval S.; Garza-Garcia, Acely; Nanji, Manoj; McElwee, Joshua J.; Ackerman, Daniel; Driscoll, Paul C.; Gems, David

2008-01-01

The DAF-2 insulin/IGF-1 receptor regulates development, metabolism, and aging in the nematode Caenorhabditis elegans. However, complex differences among daf-2 alleles complicate analysis of this gene. We have employed epistasis analysis, transcript profile analysis, mutant sequence analysis, and homology modeling of mutant receptors to understand this complexity. We define an allelic series of nonconditional daf-2 mutants, including nonsense and deletion alleles, and a putative null allele, m65. The most severe daf-2 alleles show incomplete suppression by daf-18(0) and daf-16(0) and have a range of effects on early development. Among weaker daf-2 alleles there exist distinct mutant classes that differ in epistatic interactions with mutations in other genes. Mutant sequence analysis (including 11 newly sequenced alleles) reveals that class 1 mutant lesions lie only in certain extracellular regions of the receptor, while class 2 (pleiotropic) and nonconditional missense mutants have lesions only in the ligand-binding pocket of the receptor ectodomain or the tyrosine kinase domain. Effects of equivalent mutations on the human insulin receptor suggest an altered balance of intracellular signaling in class 2 alleles. These studies consolidate and extend our understanding of the complex genetics of daf-2 and its underlying molecular biology. PMID:18245374

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

PubMed

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.

Study of vibrational modes and specific heat of wurtzite phase of BN

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

Singh, Daljit, E-mail: daljit.jt@gmail.com; Sinha, M. M.

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.

Crystal Structure of Swine Vesicular Disease Virus and Implications for Host Adaptation

PubMed Central

Fry, Elizabeth E.; Knowles, Nick J.; Newman, John W. I.; Wilsden, Ginette; Rao, Zihe; King, Andrew M. Q.; Stuart, David I.

2003-01-01

Swine vesicular disease virus (SVDV) is an Enterovirus of the family Picornaviridae that causes symptoms indistinguishable from those of foot-and-mouth disease virus. Phylogenetic studies suggest that it is a recently evolved genetic sublineage of the important human pathogen coxsackievirus B5 (CBV5), and in agreement with this, it has been shown to utilize the coxsackie and adenovirus receptor (CAR) for cell entry. The 3.0-Å crystal structure of strain UK/27/72 SVDV (highly virulent) reveals the expected similarity in core structure to those of other picornaviruses, showing most similarity to the closest available structure to CBV5, that of coxsackievirus B3 (CBV3). Features that help to cement together and rigidify the protein subunits are extended in this virus, perhaps explaining its extreme tolerance of environmental factors. Using the large number of capsid sequences available for both SVDV and CBV5, we have mapped the amino acid substitutions that may have occurred during the supposed adaptation of SVDV to a new host onto the structure of SVDV and a model of the SVDV/CAR complex generated by reference to the cryo-electron microscopy-visualized complex of CBV3 and CAR. The changes fall into three clusters as follows: one lines the fivefold pore, a second maps to the CAR-binding site and partially overlaps the site for decay accelerating factor (DAF) to bind to echovirus 7 (ECHO7), and the third lies close to the fivefold axis, where the low-density lipoprotein receptor binds to the minor group of rhinoviruses. Later changes in SVDV (post-1971) map to the first two clusters and may, by optimizing recognition of a pig CAR and/or DAF homologue, have improved the adaptation of the virus to pigs. PMID:12692248

RT 24 - Architecture, Modeling & Simulation, and Software Design

DTIC Science & Technology

2010-11-01

focus on tool extensions (UPDM, SysML, SoaML, BPMN ) Leverage “best of breed” architecture methodologies Provide tooling to support the methodology DoDAF...Capability 10 Example: BPMN 11 DoDAF 2.0 MetaModel BPMN MetaModel Mapping SysML to DoDAF 2.0 12 DoDAF V2.0 Models OV-2 SysML Diagrams Requirement

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

PubMed

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.

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

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

Depuydt, Geert; Xie, Fang; Petyuk, Vladislav A.

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. Proteomicsmore » 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.« less

Spontaneous Age-Related Neurite Branching in C. elegans

PubMed Central

Tank, Elizabeth M. H.; Rodgers, Kasey E.; Kenyon, Cynthia

2011-01-01

The analysis of morphological changes that occur in the nervous system during normal aging could provide insight into cognitive decline and neurodegenerative disease. Previous studies have suggested that the nervous system of C. elegans maintains its structural integrity with age despite the deterioration of surrounding tissues. Unexpectedly, we observed that neurons in aging animals frequently displayed ectopic branches, and that the prevalence of these branches increased with time. Within age-matched populations, the branching of mechnosensory neurons correlated with decreased response to light touch and decreased mobility. The incidence of branching was influenced by two pathways that can affect the rate of aging, the Jun kinase pathway and the insulin/IGF-1 pathway. Loss of Jun kinase signaling, which slightly shortens lifespan, dramatically increased and accelerated the frequency of neurite branching. Conversely, inhibition of the daf-2 insulin/IGF-1-like signaling pathway, which extends lifespan, delayed and suppressed branching, and this delay required DAF-16/FOXO activity. Both JNK-1 and DAF-16 appeared to act within neurons in a cell-autonomous manner to influence branching, and, through their tissue-specific expression, it was possible to disconnect the rate at which branching occurred from the overall rate of aging of the animal. Old age has generally been associated with the decline and deterioration of different tissues, except in the case of tumor cell growth. To our knowledge, this is the first indication that aging can potentiate another form of growth, the growth of neurite branches, in normal animals. PMID:21697377

Bubble performance of a novel dissolved air flotation(DAF) unit.

PubMed

Chen, Fu-tai; Peng, Feng-xian; Wu, Xiao-qing; Luan, Zhao-kun

2004-01-01

ES-DAF, a novel DAF with low cost, high reliability and easy controllability, was studied. Without a costly air saturator, ES-DAF consists of an ejector and a static mixer between the pressure side and suction side of the recycle rotary pump. The bubble size distribution in this novel unit was studied in detail by using a newly developed CCD imagination through a microscope. Compared with M-DAF under the same saturation pressure, ES-DAF can produce smaller bubble size and higher bubble volume concentration, especially in lower pressure. In addition, the bubble size decreases with the increase of reflux ratio or decrease of superficial air-water ratio. These results suggested that smaller bubbles will be formed when the initial number of nucleation sites increases by enhancing the turbulence intensity in the saturation system.

A case study of dissolved air flotation for seasonal high turbidity water in Korea.

PubMed

Kwon, S B; Ahn, H W; Ahn, C J; Wang, C K

2004-01-01

A DAF (Dissolved-Air-Flotation) process has been designed considering raw water quality characteristics in Korea. Although direct filtration is usually operated, DAF is operated when freshwater algae blooms occur or raw water turbidity becomes high. Pre-sedimentation is operated in case when the raw water turbidity is very high due to rainstorms. A main feature of this plant is that the operation mode can be changed (controlled) based on the characteristics of the raw water to optimize the effluent quality and the operation costs. Treatment capacity (surface loading rate) and efficiency of DAF was found to be better than the conventional sedimentation process. Moreover, low-density particles (algae and alum flocs) are easily separated while the removal of them by sedimentation is more difficult. One of the main concerns for DAF operation is a high raw water turbidity. DAF is not adequate for raw water, which is more turbid than 100 NTU. In order to avoid this problem, pre-sedimentation basins are installed in the DAF plant to decrease the turbidity of the DAF inflow. For simulation of the actual operation, bench and full-scale tests were performed for highly turbid water conditions. Consequently, it is suggested that pre-sedimentation with optimum coagulation prior to DAF is the appropriate treatment scheme.

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

PubMed

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.

Feeding State, Insulin and NPR-1 Modulate Chemoreceptor Gene Expression via Integration of Sensory and Circuit Inputs

PubMed Central

Gruner, Matthew; Nelson, Dru; Winbush, Ari; Hintz, Rebecca; Ryu, Leesun; Chung, Samuel H.; Kim, Kyuhyung; Gabel, Chrisopher V.; van der Linden, Alexander M.

2014-01-01

Feeding state and food availability can dramatically alter an animals' sensory response to chemicals in its environment. Dynamic changes in the expression of chemoreceptor genes may underlie some of these food and state-dependent changes in chemosensory behavior, but the mechanisms underlying these expression changes are unknown. Here, we identified a KIN-29 (SIK)-dependent chemoreceptor, srh-234, in C. elegans whose expression in the ADL sensory neuron type is regulated by integration of sensory and internal feeding state signals. We show that in addition to KIN-29, signaling is mediated by the DAF-2 insulin-like receptor, OCR-2 TRPV channel, and NPR-1 neuropeptide receptor. Cell-specific rescue experiments suggest that DAF-2 and OCR-2 act in ADL, while NPR-1 acts in the RMG interneurons. NPR-1-mediated regulation of srh-234 is dependent on gap-junctions, implying that circuit inputs regulate the expression of chemoreceptor genes in sensory neurons. Using physical and genetic manipulation of ADL neurons, we show that sensory inputs from food presence and ADL neural output regulate srh-234 expression. While KIN-29 and DAF-2 act primarily via the MEF-2 (MEF2) and DAF-16 (FOXO) transcription factors to regulate srh-234 expression in ADL neurons, OCR-2 and NPR-1 likely act via a calcium-dependent but MEF-2- and DAF-16-independent pathway. Together, our results suggest that sensory- and circuit-mediated regulation of chemoreceptor genes via multiple pathways may allow animals to precisely regulate and fine-tune their chemosensory responses as a function of internal and external conditions. PMID:25357003

Identification of Late Larval Stage Developmental Checkpoints in Caenorhabditis elegans Regulated by Insulin/IGF and Steroid Hormone Signaling Pathways

PubMed Central

Schindler, Adam J.; Baugh, L. Ryan; Sherwood, David R.

2014-01-01

Organisms in the wild develop with varying food availability. During periods of nutritional scarcity, development may slow or arrest until conditions improve. The ability to modulate developmental programs in response to poor nutritional conditions requires a means of sensing the changing nutritional environment and limiting tissue growth. The mechanisms by which organisms accomplish this adaptation are not well understood. We sought to study this question by examining the effects of nutrient deprivation on Caenorhabditis elegans development during the late larval stages, L3 and L4, a period of extensive tissue growth and morphogenesis. By removing animals from food at different times, we show here that specific checkpoints exist in the early L3 and early L4 stages that systemically arrest the development of diverse tissues and cellular processes. These checkpoints occur once in each larval stage after molting and prior to initiation of the subsequent molting cycle. DAF-2, the insulin/insulin-like growth factor receptor, regulates passage through the L3 and L4 checkpoints in response to nutrition. The FOXO transcription factor DAF-16, a major target of insulin-like signaling, functions cell-nonautonomously in the hypodermis (skin) to arrest developmental upon nutrient removal. The effects of DAF-16 on progression through the L3 and L4 stages are mediated by DAF-9, a cytochrome P450 ortholog involved in the production of C. elegans steroid hormones. Our results identify a novel mode of C. elegans growth in which development progresses from one checkpoint to the next. At each checkpoint, nutritional conditions determine whether animals remain arrested or continue development to the next checkpoint. PMID:24945623

TATN-1 Mutations Reveal a Novel Role for Tyrosine as a Metabolic Signal That Influences Developmental Decisions and Longevity in Caenorhabditis elegans

PubMed Central

Ferguson, Annabel A.; Dumas, Kathleen J.; Ritov, Vladimir B.; Matern, Dietrich; Hu, Patrick J.; Fisher, Alfred L.

2013-01-01

Recent work has identified changes in the metabolism of the aromatic amino acid tyrosine as a risk factor for diabetes and a contributor to the development of liver cancer. While these findings could suggest a role for tyrosine as a direct regulator of the behavior of cells and tissues, evidence for this model is currently lacking. Through the use of RNAi and genetic mutants, we identify tatn-1, which is the worm ortholog of tyrosine aminotransferase and catalyzes the first step of the conserved tyrosine degradation pathway, as a novel regulator of the dauer decision and modulator of the daf-2 insulin/IGF-1-like (IGFR) signaling pathway in Caenorhabditis elegans. Mutations affecting tatn-1 elevate tyrosine levels in the animal, and enhance the effects of mutations in genes that lie within the daf-2/insulin signaling pathway or are otherwise upstream of daf-16/FOXO on both dauer formation and worm longevity. These effects are mediated by elevated tyrosine levels as supplemental dietary tyrosine mimics the phenotypes produced by a tatn-1 mutation, and the effects still occur when the enzymes needed to convert tyrosine into catecholamine neurotransmitters are missing. The effects on dauer formation and lifespan require the aak-2/AMPK gene, and tatn-1 mutations increase phospho-AAK-2 levels. In contrast, the daf-16/FOXO transcription factor is only partially required for the effects on dauer formation and not required for increased longevity. We also find that the controlled metabolism of tyrosine by tatn-1 may function normally in dauer formation because the expression of the TATN-1 protein is regulated both by daf-2/IGFR signaling and also by the same dietary and environmental cues which influence dauer formation. Our findings point to a novel role for tyrosine as a developmental regulator and modulator of longevity, and support a model where elevated tyrosine levels play a causal role in the development of diabetes and cancer in people. PMID:24385923

Dafadine inhibits DAF-9 to promote dauer formation and longevity of Caenorhabditis elegans.

PubMed

Luciani, Genna M; Magomedova, Lilia; Puckrin, Rachel; Urbanus, Malene L; Wallace, Iain M; Giaever, Guri; Nislow, Corey; Cummins, Carolyn L; Roy, Peter J

2011-11-06

The DAF-9 cytochrome P450 is a key regulator of dauer formation, developmental timing and longevity in the nematode Caenorhabditis elegans. Here we describe the first identified chemical inhibitor of DAF-9 and the first reported small-molecule tool that robustly induces dauer formation in typical culture conditions. This molecule (called dafadine) also inhibits the mammalian ortholog of DAF-9(CYP27A1), suggesting that dafadine can be used to interrogate developmental control and longevity in other animals.

EFFECT OF DELAYED AUDITORY FEEDBACK, SPEECH RATE, AND SEX ON SPEECH PRODUCTION.

PubMed

Stuart, Andrew; Kalinowski, Joseph

2015-06-01

Perturbations in Delayed Auditory Feedback (DAF) and speech rate were examined as sources of disruptions in speech between men and women. Fluent adult men (n = 16) and women (n = 16) spoke at a normal and an imposed fast rate of speech with 0, 25, 50, 100, and 200 msec. DAF. The syllable rate significantly increased when participants were instructed to speak at a fast rate, and the syllable rate decreased with increasing DAF delays. Men's speech rate was significantly faster during the fast speech rate condition with a 200 msec. DAF. Disfluencies increased with increasing DAF delay. Significantly more disfluency occurred at delays of 25 and 50 msec. at the fast rate condition, while more disfluency occurred at 100 and 200 msec. in normal rate conditions. Men and women did not display differences in the number of disfluencies. These findings demonstrate sex differences in susceptibility to perturbations in DAF and speech rate suggesting feedforward/feedback subsystems that monitor vocalizations may be different between sexes.

A Non-Cell-Autonomous Role of BEC-1/BECN1/Beclin1 in Coordinating Cell-Cycle Progression and Stem Cell Proliferation during Germline Development.

PubMed

Ames, Kristina; Da Cunha, Dayse S; Gonzalez, Brenda; Konta, Marina; Lin, Feng; Shechter, Gabriel; Starikov, Lev; Wong, Sara; Bülow, Hannes E; Meléndez, Alicia

2017-03-20

The decision of stem cells to proliferate and differentiate is finely controlled. The Caenorhabditis elegans germline provides a tractable system for studying the mechanisms that control stem cell proliferation and homeostasis [1-4]. Autophagy is a conserved cellular recycling process crucial for cellular homeostasis in many different contexts [5], but its function in germline stem cell proliferation remains poorly understood. Here, we describe a function for autophagy in germline stem cell proliferation. We found that autophagy genes such as bec-1/BECN1/Beclin1, atg-16.2/ATG16L, atg-18/WIPI1/2, and atg-7/ATG7 are required for the late larval expansion of germline stem cell progenitors in the C. elegans gonad. We further show that BEC-1/BECN1/Beclin1 acts independently of the GLP-1/Notch or DAF-7/TGF-β pathways but together with the DAF-2/insulin IGF-1 receptor (IIR) signaling pathway to promote germline stem cell proliferation. Similar to DAF-2/IIR, BEC-1/BECN1/Beclin1, ATG-18/WIPI1/2, and ATG-16.2/ATG16L all promote cell-cycle progression and are negatively regulated by the phosphatase and tensin homolog DAF-18/PTEN. However, whereas BEC-1/BECN1/Beclin1 acts through the transcriptional regulator SKN-1/Nrf1, ATG-18/WIPI1/2 and ATG-16.2/ATG16L exert their function through the DAF-16/FOXO transcription factor. In contrast, ATG-7 functions in concert with the DAF-7/TGF-β pathway to promote germline proliferation and is not required for cell-cycle progression. Finally, we report that BEC-1/BECN1/Beclin1 functions non-cell-autonomously to facilitate cell-cycle progression and stem cell proliferation. Our findings demonstrate a novel non-autonomous role for BEC-1/BECN1/Beclin1 in the control of stem cell proliferation and cell-cycle progression, which may have implications for the understanding and development of therapies against malignant cell growth in the future. Copyright © 2017 Elsevier Ltd. All rights reserved.

The South Circumpolar Dorsa Argentea Formation and the Noachian-Hesperian Climate of Mars

NASA Astrophysics Data System (ADS)

Head, J. W., III; Scanlon, K. E.; Fastook, J.; Wordsworth, R. D.

2017-12-01

The Dorsa Argentea Formation (DAF), a set of geomorphologic units covering 1.5 · 106 km2 in the south circumpolar region of Mars with lobes extending along the 0° and 90°W meridians, has been interpreted as the remnants of a large Noachian-Hesperian ice sheet. Determining the extent and thermal regime of the DAF ice sheet, and the controls on its development, can therefore provide insight into the ancient martian climate. We used the Laboratoire de Météorologie Dynamique early Mars global climate model (GCM) and the University of Maine Ice Sheet Model (UMISM) glacial flow model to constrain climates that would permit both development of a south polar ice sheet of DAF-like size and shape and melting consistent with observed eskers and channels. An asymmetric south polar cold trap is a robust feature of GCM simulations with spin-axis obliquity of 15° or 25° and a 600 - 1000 mb CO2 atmosphere. The shape results from the strong dependence of surface temperature on altitude in a thicker atmosphere. Of the scenarios considered here, the shape and extent of the modeled DAF ice sheet in UMISM simulations most closely match those of the DAF when the surface water ice inventory of Mars is 20 · 106 km3 and obliquity is 15°. In climates warmed only by CO2, basal melting does not occur except when the ice inventory is larger than most estimates for early Mars. In this case, the extent of the ice sheet is also much larger than that of the DAF, and melting is more widespread than observed landforms indicate. When an idealized greenhouse gas warms the surface by at least 20° near the poles relative to CO2 alone, the extent of the ice sheet is less than that of the DAF, but strong basal melting occurs, with maxima in the locations where eskers and channels are observed. We conclude that the glaciofluvial landforms in the DAF implicate warming by a gas other than CO2 alone. Previously published exposure ages of eskers in the DAF indicate that eskers were being exposed as activity was ceasing in the equatorial valley networks, suggesting that the warming that allowed basal melting of the DAF ice sheet was broadly contemporaneous with development of the valley networks. Elevated Tharsis topography is required to produce an ice sheet with the shape of the DAF. Thus, our results are not consistent with the DAF (and the valley networks) forming before Tharsis, as recently suggested.

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

PubMed

Barna, János; Princz, Andrea; Kosztelnik, Mónika; Hargitai, Balázs; Takács-Vellai, Krisztina; Vellai, Tibor

2012-11-01

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. 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. 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.

A Conserved PHD Finger Protein and Endogenous RNAi Modulate Insulin Signaling in Caenorhabditis elegans

PubMed Central

Hoersch, Sebastian; Jensen, Morten B.; Kawli, Trupti; Kennedy, Lisa M.; Chavez, Violeta; Tan, Man-Wah; Lieb, Jason D.; Grishok, Alla

2011-01-01

Insulin signaling has a profound effect on longevity and the oxidative stress resistance of animals. Inhibition of insulin signaling results in the activation of DAF-16/FOXO and SKN-1/Nrf transcription factors and increased animal fitness. By studying the biological functions of the endogenous RNA interference factor RDE-4 and conserved PHD zinc finger protein ZFP-1 (AF10), which regulate overlapping sets of genes in Caenorhabditis elegans, we identified an important role for these factors in the negative modulation of transcription of the insulin/PI3 signaling-dependent kinase PDK-1. Consistently, increased expression of pdk-1 in zfp-1 and rde-4 mutants contributed to their reduced lifespan and sensitivity to oxidative stress and pathogens due to the reduction in the expression of DAF-16 and SKN-1 targets. We found that the function of ZFP-1 in modulating pdk-1 transcription was important for the extended lifespan of the age-1(hx546) reduction-of-function PI3 kinase mutant, since the lifespan of the age-1; zfp-1 double mutant strain was significantly shorter compared to age-1(hx546). We further demonstrate that overexpression of ZFP-1 caused an increased resistance to oxidative stress in a DAF-16–dependent manner. Our findings suggest that epigenetic regulation of key upstream signaling components in signal transduction pathways through chromatin and RNAi may have a large impact on the outcome of signaling and expression of numerous downstream genes. PMID:21980302

A conserved PHD finger protein and endogenous RNAi modulate insulin signaling in Caenorhabditis elegans.

PubMed

Mansisidor, Andres R; Cecere, Germano; Hoersch, Sebastian; Jensen, Morten B; Kawli, Trupti; Kennedy, Lisa M; Chavez, Violeta; Tan, Man-Wah; Lieb, Jason D; Grishok, Alla

2011-09-01

Insulin signaling has a profound effect on longevity and the oxidative stress resistance of animals. Inhibition of insulin signaling results in the activation of DAF-16/FOXO and SKN-1/Nrf transcription factors and increased animal fitness. By studying the biological functions of the endogenous RNA interference factor RDE-4 and conserved PHD zinc finger protein ZFP-1 (AF10), which regulate overlapping sets of genes in Caenorhabditis elegans, we identified an important role for these factors in the negative modulation of transcription of the insulin/PI3 signaling-dependent kinase PDK-1. Consistently, increased expression of pdk-1 in zfp-1 and rde-4 mutants contributed to their reduced lifespan and sensitivity to oxidative stress and pathogens due to the reduction in the expression of DAF-16 and SKN-1 targets. We found that the function of ZFP-1 in modulating pdk-1 transcription was important for the extended lifespan of the age-1(hx546) reduction-of-function PI3 kinase mutant, since the lifespan of the age-1; zfp-1 double mutant strain was significantly shorter compared to age-1(hx546). We further demonstrate that overexpression of ZFP-1 caused an increased resistance to oxidative stress in a DAF-16-dependent manner. Our findings suggest that epigenetic regulation of key upstream signaling components in signal transduction pathways through chromatin and RNAi may have a large impact on the outcome of signaling and expression of numerous downstream genes.

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

PubMed Central

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

2006-01-01

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 phenotypes. Conclusion A screen for suppressors of PI3K mutant phenotypes identified activating mutations in two known pathway components, providing insights into their regulation. In particular, the interdependence of akt-1 and pdk-1, even in activated forms, supports the existence of AGE-1-independent pathways for these phospholipid-dependent kinases. Phenotypic analysis of these alleles shows that the larval and adult outputs of AGE-1/PI3K are fully separable in these mutants. PMID:17020605

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

PubMed Central

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

Dissolved air flotation and me.

PubMed

Edzwald, James K

2010-04-01

This paper is mainly a critical review of the literature and an assessment of what we know about dissolved air flotation (DAF). A few remarks are made at the outset about the author's personal journey in DAF research, his start and its progression. DAF has been used for several decades in drinking water treatment as an alternative clarification method to sedimentation. DAF is particularly effective in treating reservoir water supplies; those supplies containing algae, natural color or natural organic matter; and those with low mineral turbidity. It is more efficient than sedimentation in removing turbidity and particles for these type supplies. Furthermore, it is more efficient in removing Giardia cysts and Cryptosporidium oocysts. In the last 20 years, fundamental models were developed that provide a basis for understanding the process, optimizing it, and integrating it into water treatment plants. The theories were tested through laboratory and pilot-plant studies. Consequently, there have been trends in which DAF pretreatment has been optimized resulting in better coagulation and a decrease in the size of flocculation tanks. In addition, the hydraulic loading rates have increased reducing the size of DAF processes. While DAF has been used mainly in conventional type water plants, there is now interest in the technology as a pretreatment step in ultrafiltration membrane plants and in desalination reverse osmosis plants. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

The Nuclear Receptor DAF-12 Regulates Nutrient Metabolism and Reproductive Growth in Nematodes

PubMed Central

Wang, Zhu; Stoltzfus, Jonathan; You, Young-jai; Ranjit, Najju; Tang, Hao; Xie, Yang; Lok, James B.; Mangelsdorf, David J.; Kliewer, Steven A.

2015-01-01

Appropriate nutrient response is essential for growth and reproduction. Under favorable nutrient conditions, the C. elegans nuclear receptor DAF-12 is activated by dafachronic acids, hormones that commit larvae to reproductive growth. Here, we report that in addition to its well-studied role in controlling developmental gene expression, the DAF-12 endocrine system governs expression of a gene network that stimulates the aerobic catabolism of fatty acids. Thus, activation of the DAF-12 transcriptome coordinately mobilizes energy stores to permit reproductive growth. DAF-12 regulation of this metabolic gene network is conserved in the human parasite, Strongyloides stercoralis, and inhibition of specific steps in this network blocks reproductive growth in both of the nematodes. Our study provides a molecular understanding for metabolic adaptation of nematodes to their environment, and suggests a new therapeutic strategy for treating parasitic diseases. PMID:25774872

Wavelets and distributed approximating functionals

NASA Astrophysics Data System (ADS)

Wei, G. W.; Kouri, D. J.; Hoffman, D. K.

1998-07-01

A general procedure is proposed for constructing father and mother wavelets that have excellent time-frequency localization and can be used to generate entire wavelet families for use as wavelet transforms. One interesting feature of our father wavelets (scaling functions) is that they belong to a class of generalized delta sequences, which we refer to as distributed approximating functionals (DAFs). We indicate this by the notation wavelet-DAFs. Correspondingly, the mother wavelets generated from these wavelet-DAFs are appropriately called DAF-wavelets. Wavelet-DAFs can be regarded as providing a pointwise (localized) spectral method, which furnishes a bridge between the traditional global methods and local methods for solving partial differential equations. They are shown to provide extremely accurate numerical solutions for a number of nonlinear partial differential equations, including the Korteweg-de Vries (KdV) equation, for which a previous method has encountered difficulties (J. Comput. Phys. 132 (1997) 233).

Experimental SSM-CVB3 infection in macaques.

PubMed

Han, Tiesuo; He, Wenqi; Song, Deguang; Zhao, Kui; Wu, Chenchen; Gao, Feng; Lu, Huijun; Gai, Xianying; Wang, Xinrui; Li, Fei; Ji, Cuicui; Lin, Xijuan

2012-02-01

To evaluate the pathogenicity of SSM-CVB3 in a macaque model. The clinical symptoms of macaques were recorded; hematological, biochemical and histopathological evaluations were completed; viral titers and neutralization titers (NT-titers) in sera were tested; and the mRNA levels of SSM-CVB3, coxsackievirus and adenovirus receptor (CAR) and decay accelerating factor (DAF) were determined. After SSM-CVB3 infection, the macaques showed a lack of activity, a poor appetite, a higher body temperature, and severe diarrhea. The macaques also developed hematuria and albuminuria at 4 to 10 days post-inoculation. Virus titers (5.1-6.5 LogTCID(50)/mL) were higher at 6 to 10 days post-inoculation, and NT-titers (6.5-7.3 Log2) reached plateaus at 8 to 14 days post-inoculation. The infected macaques developed serious anemia with decreased RBC and WBC, but the percentages of LYM were increased. The levels of CK, CK-MB, AST and ALT in the sera were 84-169 U/L, 87.6-271.1 U/L, 43-87 U/L and 43-82 U/L, respectively, and all of those were higher than normal. Histological analysis showed obvious cardiac, hepatic and renal damages in the infected macaques and the mRNA contents of SSM-CVB3, CAR and DAF in the heart, liver and kidneys of infected macaques were higher (P<0.05). This was the first report on experimental SSM-CVB3 infections in macaques with serious hepatic and renal damage, except for myocarditis. The information obtained from this study suggests that the SSM-CVB3 strain and this macaque model could be used for studying CVB3-induced cardiac, hepatic or renal diseases. Copyright © 2011 Elsevier Inc. All rights reserved.

The xenoantibody response and immunoglobulin gene expression profile of cynomolgus monkeys transplanted with hDAF-transgenic porcine hearts.

PubMed

Zahorsky-Reeves, Joanne L; Kearns-Jonker, Mary K; Lam, Tuan T; Jackson, Jeremy R; Morris, Randall E; Starnes, Vaughn A; Cramer, Donald V

2007-03-01

Recent work has indicated a role for anti-Gal alpha 1-3Gal (Gal) and anti-non-Gal xenoantibodies in the primate humoral rejection response against human-decay accelerating factor (hDAF) transgenic pig organs. Our laboratory has shown that anti-porcine xenograft antibodies in humans and non-human primates are encoded by a small number of germline IgV(H) progenitors. In this study, we extended our analysis to identify the IgV(H) genes encoding xenoantibodies in immunosuppressed cynomolgus monkeys (Macaca fascicularis) transplanted with hDAF-transgenic pig organs. Three immunosuppressed monkeys underwent heterotopic heart transplantation with hDAF porcine heart xenografts. Two of three animals were given GAS914, a poly-L-lysine derivative shown to bind to anti-Gal xenoantibodies and neutralize them. One animal rejected its heart at post-operative day (POD) 39; a second animal rejected the transplanted heart at POD 78. The third monkey was euthanized on POD 36 but the heart was not rejected. Peripheral blood leukocytes (PBL) and serum were obtained from each animal before and at multiple time points after transplantation. We analyzed the immune response by enzyme-linked immunosorbent assay (ELISA) to confirm whether anti-Gal or anti-non-Gal xenoantibodies were induced after graft placement. Immunoglobulin heavy-chain gene (V(H)) cDNA libraries were then produced and screened. We generated soluble single-chain antibodies (scFv) to establish the binding specificity of the cloned immunoglobulin genes. Despite immunosuppression, which included the use of the polymer GAS914, the two animals that rejected their hearts showed elevated levels of cytotoxic anti-pig red blood cell (RBC) antibodies and anti-pig aortic endothelial cell (PAEC) antibodies. The monkey that did not reject its graft showed a decline in serum anti-RBC, anti-PAEC, and anti-Gal xenoantibodies when compared with pre-transplant levels. A V(H)3 family gene with a high level of sequence similarity to an allele of V(H)3-11, designated V(H)3-11(cyno), was expressed at elevated levels in the monkey that was not given GAS914 and whose graft was not rejected until POD 78. IgM but not IgG xenoantibodies directed at N-acetyl lactosamine (a precursor of the Gal epitope) were also induced in this animal. We produced soluble scFv from this new gene to determine whether this antibody could bind to the Gal carbohydrate, and demonstrated that this protein was capable of blocking the binding of human serum xenoantibody to Gal oligosaccharide, as had previously been shown with human V(H)3-11 scFv. DAF-transgenic organs transplanted into cynomolgus monkeys induce anti-Gal and anti-non-Gal xenoantibody responses mediated by both IgM and IgG xenoantibodies. Anti-non-Gal xenoantibodies are induced at high levels in animals treated with GAS914. Antibodies that bind to the Gal carbohydrate and to N-acetyl lactosamine are induced in the absence of GAS914 treatment. The animal whose heart remained beating for 78 days demonstrated increased usage of an antibody encoded by a germline progenitor that is structurally related, but distinct from IGHV311. This antibody binds to the Gal carbohydrate but does not induce the rapid rejection of the xenograft when expressed at high levels as early as day 8 post-transplantation.

Plant-parasitic nematodes: towards understanding molecular players in stress responses

PubMed Central

Bournaud, Caroline; Antonino de Souza Júnior, Jose Dijair

2017-01-01

Background Plant–parasitic nematode interactions occur within a vast molecular plant immunity network. Following initial contact with the host plant roots, plant-parasitic nematodes (PPNs) activate basal immune responses. Defence priming involves the release in the apoplast of toxic molecules derived from reactive species or secondary metabolism. In turn, PPNs must overcome the poisonous and stressful environment at the plant–nematode interface. The ability of PPNs to escape this first line of plant immunity is crucial and will determine its virulence. Scope Nematodes trigger crucial regulatory cytoprotective mechanisms, including antioxidant and detoxification pathways. Knowledge of the upstream regulatory components that contribute to both of these pathways in PPNs remains elusive. In this review, we discuss how PPNs probably orchestrate cytoprotection to resist plant immune responses, postulating that it may be derived from ancient molecular mechanisms. The review focuses on two transcription factors, DAF-16 and SKN-1, which are conserved in the animal kingdom and are central regulators of cell homeostasis and immune function. Both regulate the unfolding protein response and the antioxidant and detoxification pathways. DAF-16 and SKN-1 target a broad spectrum of Caenorhabditis elegans genes coding for numerous protein families present in the secretome of PPNs. Moreover, some regulatory elements of DAF-16 and SKN-1 from C. elegans have already been identified as important genes for PPN infection. Conclusion DAF-16 and SKN-1 genes may play a pivotal role in PPNs during parasitism. In the context of their hub status and mode of regulation, we suggest alternative strategies for control of PPNs through RNAi approaches. PMID:28087659

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

PubMed Central

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

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

PubMed

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.

Temporal requirements of insulin/IGF-1 signaling for proteotoxicity protection.

PubMed

Cohen, Ehud; Du, Deguo; Joyce, Derek; Kapernick, Erik A; Volovik, Yuli; Kelly, Jeffery W; Dillin, Andrew

2010-04-01

Toxic protein aggregation (proteotoxicity) is a unifying feature in the development of late-onset human neurodegenerative disorders. Reduction of insulin/IGF-1 signaling (IIS), a prominent lifespan, developmental and reproductive regulatory pathway, protects worms from proteotoxicity associated with the aggregation of the Alzheimer's disease-linked Abeta peptide. We utilized transgenic nematodes that express human Abeta and found that late life IIS reduction efficiently protects from Abeta toxicity without affecting development, reproduction or lifespan. To alleviate proteotoxic stress in the animal, the IIS requires heat shock factor (HSF)-1 to modulate a protein disaggregase, while DAF-16 regulates a presumptive active aggregase, raising the question of how these opposing activities could be co-regulated. One possibility is that HSF-1 and DAF-16 have distinct temporal requirements for protection from proteotoxicity. Using a conditional RNAi approach, we found an early requirement for HSF-1 that is distinct from the adult functions of DAF-16 for protection from proteotoxicity. Our data also indicate that late life IIS reduction can protect from proteotoxicity when it can no longer promote longevity, strengthening the prospect that IIS reduction might be a promising strategy for the treatment of neurodegenerative disorders caused by proteotoxicity.

Concentration kinetics of secoisolariciresinol diglucoside and its biosynthetic precursor coniferin in developing flaxseed.

PubMed

Fang, Jingjing; Ramsay, Aina; Paetz, Christian; Tatsis, Evangelos C; Renouard, Sullivan; Hano, Christophe; Grand, Eric; Fliniaux, Ophélie; Roscher, Albrecht; Mesnard, Francois; Schneider, Bernd

2013-01-01

In the plant kingdom, flaxseed (Linum usitatissimum L.) is the richest source of secoisolariciresinol diglucoside (SDG), which is of great interest because of its potential health benefits for human beings. The information about the kinetics of SDG formation during flaxseed development is rare and incomplete. In this study, a reversed-phase high-performance liquid chromatography-diode array detection (HPLC-DAD) method was developed to quantify SDG and coniferin, a key biosynthetic precursor of SDG in flaxseed. Seeds from different developmental stages, which were scaled by days after flowering (DAF), were harvested. After alkaline hydrolysis, the validated HPLC method was applied to determine SDG and coniferin concentrations of flaxseed from different developing stages. Coniferin was found in the entire capsule as soon as flowering started and became undetectable 20 DAF. SDG was detected 6 DAF, and the concentration increased until maturity. On the other hand, the SDG amount in a single flaxseed approached the maximum around 25 DAF, before desiccation started. Concentration increase between 25 DAF and 35 DAF can be attributed to corresponding seed weight decrease. The biosynthesis of coniferin is not synchronous with that of SDG. Hence, the concentrations of SDG and coniferin change during flaxseed development. Copyright © 2012 John Wiley & Sons, Ltd.

Distributed approximating functional fit of the H{sub 3} {ital ab initio} potential-energy data of Liu and Siegbahn

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

Frishman, A.; Hoffman, D.K.; Kouri, D.J.

1997-07-01

We report a distributed approximating functional (DAF) fit of the {ital ab initio} potential-energy data of Liu [J. Chem. Phys. {bold 58}, 1925 (1973)] and Siegbahn and Liu [{ital ibid}. {bold 68}, 2457 (1978)]. The DAF-fit procedure is based on a variational principle, and is systematic and general. Only two adjustable parameters occur in the DAF leading to a fit which is both accurate (to the level inherent in the input data; RMS error of 0.2765 kcal/mol) and smooth ({open_quotes}well-tempered,{close_quotes} in DAF terminology). In addition, the LSTH surface of Truhlar and Horowitz based on this same data [J. Chem. Phys.more » {bold 68}, 2466 (1978)] is itself approximated using only the values of the LSTH surface on the same grid coordinate points as the {ital ab initio} data, and the same DAF parameters. The purpose of this exercise is to demonstrate that the DAF delivers a well-tempered approximation to a known function that closely mimics the true potential-energy surface. As is to be expected, since there is only roundoff error present in the LSTH input data, even more significant figures of fitting accuracy are obtained. The RMS error of the DAF fit, of the LSTH surface at the input points, is 0.0274 kcal/mol, and a smooth fit, accurate to better than 1cm{sup {minus}1}, can be obtained using more than 287 input data points. {copyright} {ital 1997 American Institute of Physics.}« less

The Dorsa Argentea Formation and the Noachian-Hesperian climate transition

NASA Astrophysics Data System (ADS)

Scanlon, K. E.; Head, J. W.; Fastook, J. L.; Wordsworth, R. D.

2018-01-01

The Dorsa Argentea Formation (DAF), a set of geomorphologic units covering ∼1.5 million square kilometers in the south circumpolar region of Mars, has been interpreted as the remnants of a large south polar ice sheet that formed near the Noachian-Hesperian boundary and receded in the early Hesperian. Determining the extent and thermal regime of the DAF ice sheet, as well as the mechanism and timing of its recession, can therefore provide insight into the ancient martian climate and the timing of the transition from a presumably thicker CO2 atmosphere to the present climate. We used the Laboratoire de Météorologie Dynamique (LMD) early Mars global climate model (GCM) and the University of Maine Ice Sheet Model (UMISM) glacial flow model to constrain climates allowing development of a south polar ice sheet of DAF-like size and shape. In addition, we modeled basal melting of this ice sheet in amounts and locations consistent with observed glaciofluvial landforms. A large, asymmetric region of ice stability surrounding the south pole is a robust feature of GCM simulations with spin-axis obliquity of 15° or 25° and a 600-1000 mb CO2 atmosphere. The shape results from the large-scale south polar topography of Mars and the strong dependence of surface temperature on altitude under a thicker atmosphere. Of the scenarios considered in this study, the extent of the modeled DAF ice sheet in UMISM simulations most closely matches that of the DAF when the surface water ice inventory of Mars is a ∼137 m global equivalent layer (GEL) and spin-axis obliquity is 15°. In climates warmed only by CO2, significant basal melting does not occur except when the ice inventory is larger than plausible estimates for early Mars. In this case, the extent of the south polar ice sheet is also much larger than that of the DAF, and basal melting is more widespread than observed landforms indicate. When an idealized greenhouse gas warms the surface by at least 20°C near the poles relative to CO2 alone, the stable extent of the ice sheet is less than that of the DAF units, but widespread basal melting occurs, with maxima in the locations where eskers are currently observed. We therefore conclude that warming by a gas other than CO2 alone was necessary to enable the construction of glaciofluvial landforms in the DAF. Previously published crater exposure ages of eskers in the DAF indicate that eskers were being exposed as activity was ceasing in the equatorial valley networks, suggesting that the warming that allowed basal melting at the edges of the DAF ice sheet were broadly contemporaneous with those in which the valley networks were carved. Finally, elevated Tharsis topography is required to produce an ice sheet with the shape of the DAF. Thus, our results are not consistent with the DAF (and the valley networks) forming before the emplacement of Tharsis, as recently suggested.

The Application of Architecture Frameworks to Modelling Exploration Operations Costs

NASA Technical Reports Server (NTRS)

Shishko, Robert

2006-01-01

Developments in architectural frameworks and system-of-systems thinking have provided useful constructs for systems engineering. DoDAF concepts, language, and formalisms, in particular, provide a natural way of conceptualizing an operations cost model applicable to NASA's space exploration vision. Not all DoDAF products have meaning or apply to a DoDAF inspired operations cost model, but this paper describes how such DoDAF concepts as nodes, systems, and operational activities relate to the development of a model to estimate exploration operations costs. The paper discusses the specific implementation to the Mission Operations Directorate (MOD) operational functions/activities currently being developed and presents an overview of how this powerful representation can apply to robotic space missions as well.

pkc-1 regulates daf-2 insulin/IGF signalling-dependent control of dauer formation in Caenorhabditis elegans.

PubMed

Monje, José M; Brokate-Llanos, Ana M; Pérez-Jiménez, Mercedes M; Fidalgo, Manuel A; Muñoz, Manuel J

2011-12-01

In Caenorhabditis elegans, the insulin/IGF pathway participates in the decision to initiate dauer development. Dauer is a diapause stage that is triggered by environmental stresses, such as a lack of nutrients. Insulin/IGF receptor mutants arrest constitutively in dauer, an effect that can be suppressed by mutations in other elements of the insulin/IGF pathway or by a reduction in the activity of the nuclear hormone receptor daf-12. We have isolated a pkc-1 mutant that acts as a novel suppressor of the dauer phenotypes caused by insulin/IGF receptor mutations. Interactions between insulin/IGF mutants and the pkc-1 suppressor mutant are similar to those described for daf-12 or the DAF-12 coregulator din-1. Moreover, we show that the expression of the DAF-12 target daf-9, which is normally elevated upon a reduction in insulin/IGF receptor activity, is suppressed in a pkc-1 mutant background, suggesting that pkc-1 could link the daf-12 and insulin/IGF pathways. pkc-1 has been implicated in the regulation of peptide neurosecretion in C. elegans. Although we demonstrate that pkc-1 expression in the nervous system regulates dauer formation, our results suggest that the requirement for pkc-1 in neurosecretion is independent of its role in modulating insulin/IGF signalling. pkc-1 belongs to the novel protein kinase C (nPKC) family, members of which have been implicated in insulin resistance and diabetes in mammals, suggesting a conserved role for pkc-1 in the regulation of the insulin/IGF pathway. © 2011 The Authors. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.

Measurement of intracellular nitric oxide (NO) production in shrimp haemocytes by flow cytometry.

PubMed

Xian, Jian-An; Guo, Hui; Li, Bin; Miao, Yu-Tao; Ye, Jian-Min; Zhang, Sheng-Peng; Pan, Xun-Bin; Ye, Chao-Xia; Wang, An-Li; Hao, Xuan-Ming

2013-12-01

A flow cytometric method to measure the production of intracellular nitric oxide (NO) was adapted for use with shrimp haemocytes. We applied fluorescent probe 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate (DAF-FM DA) for NO detection in haemocytes from the tiger shrimp Penaeus monodon, and used flow cytometry to quantify fluorescence intensity in individual haemocyte. The optimized protocol for intracellular NO analysis consists to incubate haemocytes with DAF-FM DA at 10 μM for 60 min to determine the mean fluorescence intensity. Result showed that NO was also produced in the untreated shrimp haemocytes. NO level in granular cells and semigranular cells were much higher than that in hyaline cells. Defined by different characteristic of NO content, three subsets of haemocytes were observed. Zymosan A at dose of 10 or 100 particles per haemocyte triggered higher DAF-FM fluorescence intensity in granular and semigranular cells, than PMA that had no significant impact on all three cell types. These results indicate that granular and semigranular cells are the primary cells for NO generation. Cytochalasin B significantly inhibited the NO level induced by zymosan A. NG-Monomethyl-L-arginine (L-NMMA) and diphenylene iodonium chloride (DPI) significantly suppressed the DAF-FM fluorescence in haemocytes, but apocynin could not modulate it, indicating that the DAF-FM fluorescence was closely related to the activity of NO-synthase pathway. The NO donor sodium nitroprusside (SNP) improved the DAF-FM fluorescence in haemocytes, while the NO scavenger C-PTIO (2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide) significantly decreased the fluorescence, demonstrating that the fluorescence intensity of DAF-FM is mainly dependent on the intracellular NO level.

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

PubMed Central

Wei, Chia-Cheng; Yen, Pei-Ling; Chang, Shang-Tzen; Cheng, Pei-Ling; Lo, Yi-Chen; Liao, Vivian Hsiu-Chuan

2016-01-01

Background 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. Principal Findings 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. Conclusions 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. PMID:27275864

A C. elegans mutant that lives twice as long as wild type.

PubMed

Kenyon, C; Chang, J; Gensch, E; Rudner, A; Tabtiang, R

1993-12-02

We have found that mutations in the gene daf-2 can cause fertile, active, adult Caenorhabditis elegans hermaphrodites to live more than twice as long as wild type. This lifespan extension, the largest yet reported in any organism, requires the activity of a second gene, daf-16. Both genes also regulate formation of the dauer larva, a developmentally arrested larval form that is induced by crowding and starvation and is very long-lived. Our findings raise the possibility that the longevity of the dauer is not simply a consequence of its arrested growth, but instead results from a regulated lifespan extension mechanism that can be uncoupled from other aspects of dauer formation. daf-2 and daf-16 provide entry points into understanding how lifespan can be extended.

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

PubMed

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.

Plant-parasitic nematodes: towards understanding molecular players in stress responses.

PubMed

Gillet, François-Xavier; Bournaud, Caroline; Antonino de Souza Júnior, Jose Dijair; Grossi-de-Sa, Maria Fatima

2017-03-01

Plant-parasitic nematode interactions occur within a vast molecular plant immunity network. Following initial contact with the host plant roots, plant-parasitic nematodes (PPNs) activate basal immune responses. Defence priming involves the release in the apoplast of toxic molecules derived from reactive species or secondary metabolism. In turn, PPNs must overcome the poisonous and stressful environment at the plant-nematode interface. The ability of PPNs to escape this first line of plant immunity is crucial and will determine its virulence. Nematodes trigger crucial regulatory cytoprotective mechanisms, including antioxidant and detoxification pathways. Knowledge of the upstream regulatory components that contribute to both of these pathways in PPNs remains elusive. In this review, we discuss how PPNs probably orchestrate cytoprotection to resist plant immune responses, postulating that it may be derived from ancient molecular mechanisms. The review focuses on two transcription factors, DAF-16 and SKN-1 , which are conserved in the animal kingdom and are central regulators of cell homeostasis and immune function. Both regulate the unfolding protein response and the antioxidant and detoxification pathways. DAF-16 and SKN-1 target a broad spectrum of Caenorhabditis elegans genes coding for numerous protein families present in the secretome of PPNs. Moreover, some regulatory elements of DAF-16 and SKN-1 from C. elegans have already been identified as important genes for PPN infection. DAF-16 and SKN-1 genes may play a pivotal role in PPNs during parasitism. In the context of their hub status and mode of regulation, we suggest alternative strategies for control of PPNs through RNAi approaches. © The Author 2017. Published by Oxford University Press on behalf of the Annals of Botany Company.

Fruit coloration and anthocyanin biosynthesis after bag removal in non-red and red apples (Malus × domestica Borkh.).

PubMed

Liu, Yulian; Che, Fei; Wang, Lixin; Meng, Rui; Zhang, Xiaojun; Zhao, Zhengyang

2013-01-25

In the present study, evolution of apple color (L* and a/b), the accumulation of anthocyanins and the activity of the related enzymes, phenylalanine ammonia-lyase (PAL), chalcone isomerase (CHI), dihydroflavonol4-reductase (DFR) and UDP-Glucose: flavonoid-3-O-galactosyl transferase (UFGT), were investigated in bagged non-red apple cultivars ('Granny Smith' and 'Golden Delicious') and red apple cultivars ('Starkrimon' and 'Pink Lady'). Young fruits were bagged 40-45 days after flowering (DAF), and fruits of 'Golden Delicious' and 'Starkrimon' were uncovered and exposed to light 120 DAF, while those of 'Granny Smith' and 'Pink Lady' were exposed for 160 DAF. Results showed that cyanidin 3-galactoside (cy3-gal) was the most abundant anthocyanin in both non-red and red cultivars. Level of anthocyanins was higher in 'Granny Smith' than in 'Golden Delicious', indicating that red color was easier to develop in green cultivar 'Granny Smith' than in yellow cultivar 'Golden Delicious' after bag removal. The cy3-gal accumulation of non-red cultivars tested was not significantly correlated with PAL, CHI and DFR activity, but was significantly correlated with UFGT activity. During the reddening of non-red apples, UFGT may be the more important factor in the anthocyanin biosynthesis.

Community environmental factors are associated with disability in older adults with functional limitations: the MOST study.

PubMed

Keysor, Julie J; Jette, Alan M; LaValley, Michael P; Lewis, Cora E; Torner, James C; Nevitt, Michael C; Felson, Dave T

2010-04-01

There is limited evidence supporting the hypothesized environment-disability link. The objectives of this study were to (a) identify the prevalence of community mobility barriers and transportation facilitators and (b) examine whether barriers and facilitators were associated with disability among older adults with functional limitations. Four hundred and thirty-five participants aged 65+ years old with functional limitations were recruited from the Multicenter Osteoarthritis Study, a prospective study of community-dwelling adults with or at risk of developing symptomatic knee osteoarthritis. Presence of community barriers and facilitators was ascertained by the Home and Community Environment survey. Two domains of disability, (a) daily activity limitation (DAL) and (b) daily activity frequency (DAF), were assessed with the Late-Life Disability Instrument. Covariates included age, gender, education, race, comorbidity, body mass index, knee pain, and functional limitation. Multivariable logistic regression was used to examine adjusted associations of community factors with presence of DAL and DAF. Approximately one third of the participants lived in a community with high mobility barriers and low transportation facilitators. High mobility barriers was associated with greater odds of DAL (odds ratio [OR] = 2.0, 95% confidence interval [CI] 1.2-3.1) after adjusting for covariates, and high transportation facilitators was associated with lower odds of DAL (OR = 0.5, 95% CI 0.3-0.8) but not with DAF in adjusted models. People with functional limitations who live in communities that were more restrictive felt more limited in doing daily activities but did not perform these daily activities any less frequently.

A carbon dioxide avoidance behavior is integrated with responses to ambient oxygen and food in Caenorhabditis elegans

PubMed Central

Bretscher, Andrew Jonathan; Busch, Karl Emanuel; de Bono, Mario

2008-01-01

Homeostasis of internal carbon dioxide (CO2) and oxygen (O2) levels is fundamental to all animals. Here we examine the CO2 response of the nematode Caenorhabditis elegans. This species inhabits rotting material, which typically has a broad CO2 concentration range. We show that well fed C. elegans avoid CO2 levels above 0.5%. Animals can respond to both absolute CO2 concentrations and changes in CO2 levels within seconds. Responses to CO2 do not reflect avoidance of acid pH but appear to define a new sensory response. Sensation of CO2 is promoted by the cGMP-gated ion channel subunits TAX-2 and TAX-4, but other pathways are also important. Robust CO2 avoidance in well fed animals requires inhibition of the DAF-16 forkhead transcription factor by the insulin-like receptor DAF-2. Starvation, which activates DAF-16, strongly suppresses CO2 avoidance. Exposure to hypoxia (<1% O2) also suppresses CO2 avoidance via activation of the hypoxia-inducible transcription factor HIF-1. The npr-1 215V allele of the naturally polymorphic neuropeptide receptor npr-1, besides inhibiting avoidance of high ambient O2 in feeding C. elegans, also promotes avoidance of high CO2. C. elegans integrates competing O2 and CO2 sensory inputs so that one response dominates. Food and allelic variation at NPR-1 regulate which response prevails. Our results suggest that multiple sensory inputs are coordinated by C. elegans to generate different coherent foraging strategies. PMID:18524954

A carbon dioxide avoidance behavior is integrated with responses to ambient oxygen and food in Caenorhabditis elegans.

PubMed

Bretscher, Andrew Jonathan; Busch, Karl Emanuel; de Bono, Mario

2008-06-10

Homeostasis of internal carbon dioxide (CO2) and oxygen (O2) levels is fundamental to all animals. Here we examine the CO2 response of the nematode Caenorhabditis elegans. This species inhabits rotting material, which typically has a broad CO2 concentration range. We show that well fed C. elegans avoid CO2 levels above 0.5%. Animals can respond to both absolute CO2 concentrations and changes in CO2 levels within seconds. Responses to CO2 do not reflect avoidance of acid pH but appear to define a new sensory response. Sensation of CO2 is promoted by the cGMP-gated ion channel subunits TAX-2 and TAX-4, but other pathways are also important. Robust CO2 avoidance in well fed animals requires inhibition of the DAF-16 forkhead transcription factor by the insulin-like receptor DAF-2. Starvation, which activates DAF-16, strongly suppresses CO2 avoidance. Exposure to hypoxia (<1% O2) also suppresses CO2 avoidance via activation of the hypoxia-inducible transcription factor HIF-1. The npr-1 215V allele of the naturally polymorphic neuropeptide receptor npr-1, besides inhibiting avoidance of high ambient O2 in feeding C. elegans, also promotes avoidance of high CO2. C. elegans integrates competing O2 and CO2 sensory inputs so that one response dominates. Food and allelic variation at NPR-1 regulate which response prevails. Our results suggest that multiple sensory inputs are coordinated by C. elegans to generate different coherent foraging strategies.

Integrated processes for produced water polishing: Enhanced flotation/sedimentation combined with advanced oxidation processes.

PubMed

Jiménez, Silvia; Micó, María M; Arnaldos, Marina; Ferrero, Enrique; Malfeito, Jorge J; Medina, Francisco; Contreras, Sandra

2017-02-01

In this study, bench scale dissolved air flotation (DAF) and settling processes have been studied and compared to a novel flotation technology based on the use of glass microspheres of limited buoyancy and its combination with conventional DAF, (Enhanced DAF or E-DAF). They were evaluated as pretreatments for advanced oxidation processes (AOPs) to polish produced water (PW) for reuse purposes. Settling and E-DAF without air injection showed adequate turbidity and oil and grease (O&G) removals, with eliminations higher than 87% and 90% respectively, employing 70 mg L -1 of FeCl 3 and 83 min of settling time, and 57.9 mg L -1 of FeCl 3 , 300 mg L -1 of microspheres and a flocculation rate of 40 rpm in the E-DAF process. A linear correlation was observed between final O&G concentration and turbidity after E-DAF. In order to polish the O&G content of the effluent even further, to remove soluble compounds as phenol and to take advantage of residual iron after these treatments, Fenton and photo-Fenton reactions were essayed. After 6 h of the Fenton reaction at pH 3, the addition of 1660 mg L -1 of H 2 O 2 and 133 mg L -1 of iron showed a maximum O&G elimination of 57.6% and a phenol removal up to 80%. Photo-Fenton process showed better results after 3 h, adding 600 mg L -1 of H 2 O 2 and 300 mg L -1 of iron, at pH 3, with a higher fraction of elimination of the O&G content (73.7%) and phenol (95%) compared to the conventional Fenton process. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

PubMed

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.

Co-option of the hormone-signalling module dafachronic acid-DAF-12 in nematode evolution.

PubMed

Bento, Gilberto; Ogawa, Akira; Sommer, Ralf J

2010-07-22

Morphological novelties are lineage-specific traits that serve new functions. Developmental polyphenisms have been proposed to be facilitators of phenotypic evolution, but little is known about the interplay between the associated genetic and environmental factors. Here, we study two alternative morphologies in the mouth of the nematode Pristionchus pacificus and the formation of teeth-like structures that are associated with bacteriovorous feeding and predatory behaviour on fungi and other worms. These teeth-like denticles represent an evolutionary novelty, which is restricted to some members of the nematode family Diplogastridae but is absent from Caenorhabditis elegans and related nematodes. We show that the mouth dimorphism is a polyphenism that is controlled by starvation and the co-option of an endocrine switch mechanism. Mutations in the nuclear hormone receptor DAF-12 and application of its ligand, the sterol hormone dafachronic acid, strongly influence this switch mechanism. The dafachronic acid-DAF-12 module has been shown to control the formation of arrested dauer larvae in both C. elegans and P. pacificus, as well as related life-history decisions in distantly related nematodes. The comparison of dauer formation and mouth morphology switch reveals that different thresholds of dafachronic acid signalling provide specificity. This study shows how hormonal signalling acts by coupling environmental change and genetic regulation and identifies dafachronic acid as a key hormone in nematode evolution.

REMOVAL OF HUMICSUBSTANCES AND ALGAE BY DISSOLVED AIR FLOTATION

EPA Science Inventory

Dissolved air flotation (DAF) is used in place of conventional gravity settling as a means to separate low density floc particles from water. The following objectives were: (1) to compare DAF to conventional water treatment of coagulation-flocculation followed by gravity settling...

Accumulation of long-lived mRNAs associated with germination in embryos during seed development of rice

PubMed Central

Sano, Naoto; Ono, Hanako; Murata, Kazumasa; Yamada, Tetsuya; Hirasawa, Tadashi; Kanekatsu, Motoki

2015-01-01

Mature dry seeds contain translatable mRNAs called long-lived mRNAs. Early studies have shown that protein synthesis during the initial phase of seed germination occurs from long-lived mRNAs, without de novo transcription. However, the gene expression systems that generate long-lived mRNAs in seeds are not well understood. To examine the accumulation of long-lived mRNAs in developing rice embryos, germination tests using the transcriptional inhibitor actinomycin D (Act D) were performed with the Japonica rice cultivar Nipponbare. Although over 70% of embryos at 10 days after flowering (DAF) germinated in the absence of the inhibitor, germination was remarkably impaired in embryos treated with Act D. In contrast, more than 70% of embryos at 20, 25, 30 and 40 DAF germinated in the presence of Act D. The same results were obtained when another cultivar, Koshihikari, was used, indicating that the long-lived mRNAs required for germination predominantly accumulate in embryos between 10 and 20 DAF during seed development. RNA-Seq identified 529 long-lived mRNA candidates, encoding proteins such as ABA, calcium ion and phospholipid signalling-related proteins, and HSP DNA J, increased from 10 to 20 DAF and were highly abundant in 40 DAF embryos of Nipponbare and Koshihikari. We also revealed that these long-lived mRNA candidates are clearly up-regulated in 10 DAF germinating embryos after imbibition, suggesting that the accumulation of these mRNAs in embryos is indispensable for the induction of germination. The findings presented here may facilitate in overcoming irregular seed germination or producing more vigorous seedlings. PMID:25941326

Simultaneous determination of reactive oxygen and nitrogen species in mitochondrial compartments of apoptotic HepG2 cells and PC12 cells based on microchip electrophoresis-laser-induced fluorescence.

PubMed

Chen, Zhenzhen; Li, Qingling; Sun, Qianqian; Chen, Hao; Wang, Xu; Li, Na; Yin, Miao; Xie, Yanxia; Li, Hongmin; Tang, Bo

2012-06-05

Determination of intracellular bioactive species will afford beneficial information related to cell metabolism, signal transduction, cell function, and disease treatment. In this study, the first application of a microchip electrophoresis-laser-induced fluorescence (MCE-LIF) method for concurrent determination of reactive oxygen species (ROS) and reactive nitrogen species (RNS), i.e., superoxide (O(2)(-•)) and nitric oxide (NO) in mitochondria, was developed using fluorescent probes 2-chloro-1,3-dibenzothiazolinecyclohexene (DBZTC) and 3-amino,4-aminomethyl-2',7'-difluorescein (DAF-FM), respectively. Potential interference of intracellular dehydroascorbic acid (DHA) and ascorbic acid (AA) for NO detection with DAF-FM was eliminated through oxidation of AA with the addition of ascorbate oxidase, followed by subsequent MCE separation. Fluorescent products of O(2)(-•) and NO, DBZTC oxide (DBO), and DAF-FM triazole (DAF-FMT) showed excellent baseline separation within 1 min with a running buffer of 40 mM Tris solution (pH 7.4) and a separating electric field of 500 V/cm. The levels of DBO and DAF-FMT in mitochondria isolated from normal HepG2 cells and PC12 cells were evaluated using this method. Furthermore, the changes of DBO and DAF-FMT levels in mitochondria isolated from apoptotic HepG2 cells and PC12 cells could also be detected. The current approach was proved to be simple, fast, reproducible, and efficient. Measurement of the two species with the method will be beneficial to understand ROS/RNS distinctive functions. In addition, it will provide new insights into the role that both species play in biological systems.

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

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

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

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 restrictionmore » (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.« less

Biosynthesis of the Caenorhabditis elegans dauer pheromone.

PubMed

Butcher, Rebecca A; Ragains, Justin R; Li, Weiqing; Ruvkun, Gary; Clardy, Jon; Mak, Ho Yi

2009-02-10

To sense its population density and to trigger entry into the stress-resistant dauer larval stage, Caenorhabditis elegans uses the dauer pheromone, which consists of ascaroside derivatives with short, fatty acid-like side chains. Although the dauer pheromone has been studied for 25 years, its biosynthesis is completely uncharacterized. The daf-22 mutant is the only known mutant defective in dauer pheromone production. Here, we show that daf-22 encodes a homolog of human sterol carrier protein SCPx, which catalyzes the final step in peroxisomal fatty acid beta-oxidation. We also show that dhs-28, which encodes a homolog of the human d-bifunctional protein that acts just upstream of SCPx, is also required for pheromone production. Long-term daf-22 and dhs-28 cultures develop dauer-inducing activity by accumulating less active, long-chain fatty acid ascaroside derivatives. Thus, daf-22 and dhs-28 are required for the biosynthesis of the short-chain fatty acid-derived side chains of the dauer pheromone and link dauer pheromone production to metabolic state.

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

PubMed

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.

Comparison of inclined plate sedimentation and dissolved air flotation for the minimisation of subsequent nitrogenous disinfection by-product formation.

PubMed

Chu, Wen-Hai; Gao, Nai-Yun; Templeton, Michael R; Yin, Da-Qiang

2011-04-01

The formation of disinfection by-products (DBPs), including both nitrogenous disinfection by-products (N-DBPs) and carbonaceous disinfection by-products (C-DBPs), was investigated upon chlorination of water samples following two treatment processes: (i) coagulation-inclined plate sedimentation (IPS)-filtration and (ii) coagulation-dissolved air flotation (DAF)-filtration. The removal of algae, dissolved organic nitrogen (DON), dissolved organic carbon (DOC) and UV(254) by coagulation-DAF-filtration was superior to coagulation-IPS-filtration. On average, 53%, 53% and 31% of DOC, DON and UV(254) were removed by coagulation-DAF-filtration process, which were higher than 47%, 31% and 27% of that by coagulation-IPS-filtration process. Additionally, coagulation-IPS-filtration performed less well at removing the low molecular weight organics than coagulation-DAF-filtration process. The concentrations of chloroform, dichloroacetamide (DCAcAm) and dichloroacetonitrile (DCAN) formed during chlorination after coagulation-DAF-filtration reached their maximum values of 13, 1.5 and 4.7μgL(-1), respectively, and were lower than those after coagulation-IPS-filtration with the maximum detected levels of 17, 2.9 and 6.3μgL(-1). However, the trichloronitromethane (TCNM) concentration after the two processes was similar, suggesting that DON may have less of a contribution to TCNM formation than DCAcAm and DCAN. Copyright © 2011 Elsevier Ltd. All rights reserved.

TsDAF-21/Hsp90 is expressed in all examined stages of Trichinella spiralis

USDA-ARS?s Scientific Manuscript database

Trichinella is an important parasitic nematode of animals worldwide. Heat shock proteins are ubiquitous in nature and allow organisms to quickly respond to environmental stress. A portion of the Tsdaf-21 gene, a Caenorhabditis elegans daf-21 homologue encoding heat-shock protein 90 (Hsp90) was clone...

Delayed Auditory Feedback and Movement

ERIC Educational Resources Information Center

Pfordresher, Peter Q.; Dalla Bella, Simone

2011-01-01

It is well known that timing of rhythm production is disrupted by delayed auditory feedback (DAF), and that disruption varies with delay length. We tested the hypothesis that disruption depends on the state of the movement trajectory at the onset of DAF. Participants tapped isochronous rhythms at a rate specified by a metronome while hearing DAF…

Hydrothermal liquefaction of harvested high-ash low-lipid algal biomass from Dianchi Lake: effects of operational parameters and relations of products.

PubMed

Tian, Chunyan; Liu, Zhidan; Zhang, Yuanhui; Li, Baoming; Cao, Wei; Lu, Haifeng; Duan, Na; Zhang, Li; Zhang, Tingting

2015-05-01

Hydrothermal liquefaction (HTL) allows a direct conversion of algal biomass into biocrude oil, not only solving the environmental issues caused by the over-growing algae but also producing renewable energy. This study reports HTL of algae after separation from eutrophicated Dianchi Lake in China. Conversion efficiency was studied under different operational conditions via an orthogonal design, including holding temperature (HT) (260-340 °C), retention time (RT) (30-90 min) and total solid (TS) (10-20%). A highest biocrude oil yield (18.4%, dry ash-free basis, daf) was achieved at 300 °C, 60 min, and 20% (TS), due to the low contents of lipids (1.9%, daf) and proteins (24.8%, daf), and high contents of ash (41.6%, dry basis) and carbohydrates (71.8%, daf). Operational parameters significantly affected the biocrude yields, and chemical distribution of HTL products. The biocrude production also related to other HTL products, and involved chemical reactions, such as deoxygenation and/or denitrogenation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Enterprise application architecture development based on DoDAF and TOGAF

NASA Astrophysics Data System (ADS)

Tao, Zhi-Gang; Luo, Yun-Feng; Chen, Chang-Xin; Wang, Ming-Zhe; Ni, Feng

2017-05-01

For the purpose of supporting the design and analysis of enterprise application architecture, here, we report a tailored enterprise application architecture description framework and its corresponding design method. The presented framework can effectively support service-oriented architecting and cloud computing by creating the metadata model based on architecture content framework (ACF), DoDAF metamodel (DM2) and Cloud Computing Modelling Notation (CCMN). The framework also makes an effort to extend and improve the mapping between The Open Group Architecture Framework (TOGAF) application architectural inputs/outputs, deliverables and Department of Defence Architecture Framework (DoDAF)-described models. The roadmap of 52 DoDAF-described models is constructed by creating the metamodels of these described models and analysing the constraint relationship among metamodels. By combining the tailored framework and the roadmap, this article proposes a service-oriented enterprise application architecture development process. Finally, a case study is presented to illustrate the results of implementing the tailored framework in the Southern Base Management Support and Information Platform construction project using the development process proposed by the paper.

Dissolved air flotation as a potential treatment process to remove Giardia cysts from anaerobically treated sewage.

PubMed

Santos, Priscila Ribeiro Dos; Daniel, Luiz Antonio

2017-10-01

Controlling Giardia cysts in sewage is an essential barrier for public health protection, reducing possible routes of protozoa transmission. The aim of this study was to evaluate the capability of dissolved air flotation (DAF), on a bench scale, to remove Giardia cysts from anaerobic effluent. Moreover, removals of indicator microorganisms and physical variables were also investigated. Flocculation conditions were studied, associating different flocculation times with different mean velocity gradients. DAF treatment achieved mean log removals in the range of 2.52-2.62 for Giardia cysts, depending on the flocculation condition. No statistical differences were observed among the flocculation conditions in terms of cyst removal. Low levels of turbidity and apparent color obtained from the treated effluent may indicate good treatment conditions for the DAF process in cyst removal. Indicator microorganisms were not able to predict the parasitological quality of the wastewater treated by flotation in terms of cyst concentrations. The DAF process provided an effective barrier to control cysts from sewage, which is an important parasite source.

Individual Variability in Delayed Auditory Feedback Effects on Speech Fluency and Rate in Normally Fluent Adults

ERIC Educational Resources Information Center

Chon, HeeCheong; Kraft, Shelly Jo; Zhang, Jingfei; Loucks, Torrey; Ambrose, Nicoline G.

2013-01-01

Purpose: Delayed auditory feedback (DAF) is known to induce stuttering-like disfluencies (SLDs) and cause speech rate reductions in normally fluent adults, but the reason for speech disruptions is not fully known, and individual variation has not been well characterized. Studying individual variation in susceptibility to DAF may identify factors…

Delayed Auditory Feedback in the Treatment of Stuttering: Clients as Consumers

ERIC Educational Resources Information Center

Van Borsel, John; Reunes, Gert; Van den Bergh, Nathalie

2003-01-01

Purpose: To investigate the effect of repeated exposure to delayed auditory feedback (DAF) during a 3-month period outside a clinical environment and with only minimal clinical guidance on speech fluency in people who stutter. Method: A pretest-post-test design was used with repeated exposure to DAF during 3 months as the independent variable.…

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

DTIC Science & Technology

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

Frequency of paroxysmal nocturnal hemoglobinuria in patients attended in Belém, Pará, Brazil

PubMed Central

de Brito Junior, Lacy Cardoso; Cardoso, Maria do Socorro de Oliveira; Rocha, Euzamar Gaby; Anijar, Herika; Cunha, Mariana; Saraiva, João Carlos Pina

2011-01-01

Background Paroxysmal nocturnal hemoglobinuria is a hematological disease with complex physiopathology. It is genetically characterized by a somatic mutation in the PIG-A gene (phosphatidylinositol glycan anchor biosynthesis, class A), in which the best known antigens are DAF (decay accelerating factor or CD55) and MIRL (membrane inhibitor of reactive lysis or CD59). Objective To determine the frequency of paroxysmal nocturnal hemoglobinuria in patients attended at the HEMOPA foundation from November 2008 to July 2009. Method Thirty patients, with ages ranging from two to 79 years old and suspected of having paroxysmal nocturnal hemoglobinuria were examined. All patients were immunophenotyped by flow cytometry for the CD5, CD59, CD16 and CD45 antigens. Results Paroxysmal nocturnal hemoglobinuria was identified in nine of the thirty patients investigated. Another 3 cases had inconclusive results with CD59-negative labeling only for neutrophils. The highest frequency of paroxysmal nocturnal hemoglobinuria patients (7/9) and inconclusive cases (2/3) were between 19 years old and 48 years old, with a median of 28 years. Conclusion These results show the importance of flow cytometry to identify cases in which patients are deficient in only one antigen (CD59). PMID:23284241

Hydrophobically-associating cationic polymers as micro-bubble surface modifiers in dissolved air flotation for cyanobacteria cell separation.

PubMed

Yap, R K L; Whittaker, M; Diao, M; Stuetz, R M; Jefferson, B; Bulmus, V; Peirson, W L; Nguyen, A V; Henderson, R K

2014-09-15

Dissolved air flotation (DAF), an effective treatment method for clarifying algae/cyanobacteria-laden water, is highly dependent on coagulation-flocculation. Treatment of algae can be problematic due to unpredictable coagulant demand during blooms. To eliminate the need for coagulation-flocculation, the use of commercial polymers or surfactants to alter bubble charge in DAF has shown potential, termed the PosiDAF process. When using surfactants, poor removal was obtained but good bubble adherence was observed. Conversely, when using polymers, effective cell removal was obtained, attributed to polymer bridging, but polymers did not adhere well to the bubble surface, resulting in a cationic clarified effluent that was indicative of high polymer concentrations. In order to combine the attributes of both polymers (bridging ability) and surfactants (hydrophobicity), in this study, a commercially-available cationic polymer, poly(dimethylaminoethyl methacrylate) (polyDMAEMA), was functionalised with hydrophobic pendant groups of various carbon chain lengths to improve adherence of polymer to a bubble surface. Its performance in PosiDAF was contrasted against commercially-available poly(diallyl dimethyl ammonium chloride) (polyDADMAC). All synthesised polymers used for bubble surface modification were found to produce positively charged bubbles. When applying these cationic micro-bubbles in PosiDAF, in the absence of coagulation-flocculation, cell removals in excess of 90% were obtained, reaching a maximum of 99% cell removal and thus demonstrating process viability. Of the synthesised polymers, the polymer containing the largest hydrophobic functionality resulted in highly anionic treated effluent, suggesting stronger adherence of polymers to bubble surfaces and reduced residual polymer concentrations. Copyright © 2014 Elsevier Ltd. All rights reserved.

Removal of pharmaceutical residue in municipal wastewater by DAF (dissolved air flotation)-MBR (membrane bioreactor) and ozone oxidation.

PubMed

Choi, Miyoung; Choi, Dong Whan; Lee, Jung Yeol; Kim, Young Suk; Kim, Bun Su; Lee, Byoung Ho

2012-01-01

Growing attention is given to pharmaceutical residue in the water environment. It is known that pharmaceuticals are able to survive from a series of wastewater treatment processes. Concerns regarding pharmaceutical residues are attributed to the fact that they are being detected in water and sediment environment ubiquitously. Pharmaceutical treatment using a series of wastewater treatment processes of the DAF (dissolved air flotation)-MBR (membrane bioreactor)-ozone oxidation was conducted in the study. DAF, without addition of coagulant, could remove COD(cr) (chemical oxygen demand by Cr) up to over 70%, BOD 73%, SS 83%, T-N 55%, NH₄(+) 23%, and T-P 65% in influent of municipal wastewater. Average removal rates of water quality parameters by the DAF-MBR system were very high, e.g. COD(cr) 95.88%, BOD₅ 99.66%, COD(mn) (chemical oxygen demand by Mn) 93.63%, T-N 69.75%, NH₄-N 98.46%, T-P 78.23%, and SS 99.51%, which satisfy effluent water quality standards. Despite the high removal rate of the wastewater treatment system, pharmaceuticals were eliminated to be about 50-99% by the MBR system, depending on specific pharmaceuticals. Ibuprofen was well removed by MBR system up to over 95%, while removal rate of bezafibrate ranged between 50 and 90%. With over 5 mg/l of ozone oxidation, most pharmaceuticals which survived the DAF-MBR process were removed completely or resulted in very low survival rate within the range of few micrograms per litre. However, some pharmaceuticals such as bezafibrate and naproxen tended to be resistant to ozone oxidation.

Investigation of Poultry Waste for Anaerobic Digestion: A Case Study

NASA Astrophysics Data System (ADS)

Salam, Christopher R.

Anaerobic Digestion (AD) is a biological conversion technology which is being used to produce bioenergy all over the world. This energy is created from biological feedstocks, and can often use waste products from various food and agricultural processors. Biogas from AD can be used as a fuel for heating or for co-generation of electricity and heat and is a renewable substitute to using fossil fuels. Nutrient recycling and waste reduction are additional benefits, creating a final product that can be used as a fertilizer in addition to energy benefits. This project was conducted to investigate the viability of three turkey production wastes as AD feedstock: two turkey litters and a material separated from the turkey processing wastewater using dissolved air flotation (DAF) process. The DAF waste contained greases, oils and other non-commodity portions of the turkey. Using a variety of different process methods, types of bacteria, loading rates and food-to-microorganism ratios, optimal loading rates for the digestion of these three materials were obtained. In addition, the co-digestion of these materials revealed additional energy benefits. In this study, batch digestion tests were carried out to treat these three feedstocks, using mesophilic and thermophilic bacteria, using loading rates of 3 and 6 gVS/L They were tested separately and also as a mixture for co-digestion. The batch reactor used in this study had total and working volumes of 1130 mL and 500 mL, respectively. The initial organic loading was set to be 3 gVS/L, and the food to microorganism ratio was either 0.6 or 1.0 for different treatments based on the characteristics of each material. Only thermophilic (50 +/- 2ºC) temperatures were tested for the litter and DAF wastes in continuous digestion, but mesophilic and thermophilic batch digestion experiments were conducted. The optimum digestion time for all experiments was 14 days. The biogas yields of top litter, mixed litter, and DAF waste under mesophilic batch conditions all at 3 gVS/L loading were determined to be 148.6 +/- 7.82, 176.5 +/- 11.1 and 542.0 +/- 37.9 mL/ gVS, respectively and were 201.9 +/- 10.0, 210.4 +/- 29.3, and 419.3 +/- 12.1 mL/gVS, respectively, for initial loading of 6 gVS/L. Under thermophilic batch conditions, the top litter, mixed litter, and DAF waste had the biogas yields of 255.3 +/- 7.9, 313.4 +/- 30.1and 297.4 +/- 33.8 mL/gVS for loading rate of 3 gVS/L and 233.8 +/- 45.3, 306.5 +/- 11.8 and 185.1 +/- 0.85 mL/gVS for loading rate of 6 gVS/L. The biogas yields from co-digestion of the mixed litter and DAF waste at 3 gVS/L were 461.8 +/- 41.3 mL/gVS under thermophilic conditions. The results from batch anaerobic digestion tests were then used for designing continuous digestion experiments. All the continuous digestion experiments were conducted by using an Anaerobic Phase Solids (APS) digester system operated at a thermophilic temperature. The total volume of the continuous digester system was 4.8 L and the working volume was around 4.4 L. The APS digester system had two hydrolysis reactors and one biogasification reactor. Feedstock was loaded into the hydrolysis reactors in batches. The feedstock digestion time was 14 days and the average organic loading rate (OLR) of the system was 3 gVS/L/day. The experiment has three distinct feedstock stages, first with turkey litter waste, a co-digestion of DAF and turkey litter waste, followed by DAF waste. The biogas yields were determined to be 305.2 +/- 70.6 mL/gVS/d for turkey mixed litter, 455.8 +/- 77.2 mL/gVS/d during the mixture of mixed litter and DAF waste, and 382.0 +/- 39.6 mL/gVS for DAF waste. The biogas yields from the thermophilic batch test yields compare with that of the continuous digester yields. For experiments utilizing turkey litter, batch tests yielded 313.4 +/- 30.1mL/gVS biogas and 305.2 +/- 70.6 mL/gVS/d for continuous experiments. For experiments using codigestion of turkey litter and DAF waste, batches yielded 461.8 +/- 41.3 mL/gVS biogas comparing well to continuous digester operation that yielded 455.8 +/- 77.2 mL/gVS/d. It was mainly in the case for DAF that batch vs. continuous digester testing yielded a significant difference in performance. For experiments using DAF waste, batches yielded 297.4 +/- 33.8 mL/gVS biogas and continuous digester operation yielded 455.8 +/- 77.2 mL/gVS/d. For a case study on the APS digester system, mesophilic DAF waste was chosen as the optimum substrate. Using this material and reactor condition, a case study was built using provided information and experimental results to build a simulation. A reactor site needed to process 11,800 kgVS of DAF waste would require 4,800 m3 of tank volume, and use nearly 4,000 m3 as working volume. This reactor was modeled after a 2 stage APS reactor, with 2 hydrolysis reactors and 1 biogasification reactor, and had a 14 day retention time and a 3 gVS/L/d organic loading rate. The expected biogas output was 550 mL/gVS, and expected waste reduction was 20%. The reactor would produce 7,113 m3/d of biogas, and would be burned for 127,223 MJ/d.

Functional Identification and Characterization of the Brassica Napus Transcription Factor Gene BnAP2, the Ortholog of Arabidopsis Thaliana APETALA2

PubMed Central

Xiong, Zhiyong; Chen, Chunli; Wang, Lijun; Yu, Jingyin; Lu, Changming; Wei, Wenhui

2012-01-01

BnAP2, an APETALA2 (AP2)-like gene, has been isolated from Brassica napus cultivar Zhongshuang 9. The cDNA of BnAP2, with 1, 299 bp in length, encoded a transcription factor comprising of 432 amino acid residues. Results from complementary experiment indicated that BnAP2 was completely capable of restoring the phenotype of Arabidopsis ap2-11 mutant. Together with the sequence and expression data, the complementation data suggested that BnAP2 encodes the ortholog of AtAP2. To address the transcriptional activation of BnAP2, we performed transactivation assays in yeast. Fusion protein of BnAP2 with GAL4 DNA binding domain strongly activated transcription in yeast, and the transactivating activity of BnAP2 was localized to the N-terminal 100 amino acids. To further study the function of BnAP2 involved in the phenotype of B. napus, we used a transgenic approach that involved targeted RNA interference (RNAi) repression induced by ihp-RNA. Floral various phenotype defectives and reduced female fertility were observed in B. napus BnAP2-RNAi lines. Loss of the function of BnAP2 gene also resulted in delayed sepal abscission and senescence with the ethylene-independent pathway. In the strong BnAP2-RNAi lines, seeds showed defects in shape, structure and development and larger size. Strong BnAP2-RNAi and wild-type seeds initially did not display a significant difference in morphology at 10 DAF, but the development of BnAP2-RNAi seeds was slower than that of wild type at 20 DAF, and further at 30 DAF, wild-type seeds were essentially at their final size, whereas BnAP2-RNAi seeds stopped growing and developing and gradually withered. PMID:22479468

Functional identification and characterization of the Brassica napus transcription factor gene BnAP2, the ortholog of Arabidopsis thaliana APETALA2.

PubMed

Yan, Xiaohong; Zhang, Lei; Chen, Bo; Xiong, Zhiyong; Chen, Chunli; Wang, Lijun; Yu, Jingyin; Lu, Changming; Wei, Wenhui

2012-01-01

BnAP2, an APETALA2 (AP2)-like gene, has been isolated from Brassica napus cultivar Zhongshuang 9. The cDNA of BnAP2, with 1, 299 bp in length, encoded a transcription factor comprising of 432 amino acid residues. Results from complementary experiment indicated that BnAP2 was completely capable of restoring the phenotype of Arabidopsis ap2-11 mutant. Together with the sequence and expression data, the complementation data suggested that BnAP2 encodes the ortholog of AtAP2. To address the transcriptional activation of BnAP2, we performed transactivation assays in yeast. Fusion protein of BnAP2 with GAL4 DNA binding domain strongly activated transcription in yeast, and the transactivating activity of BnAP2 was localized to the N-terminal 100 amino acids. To further study the function of BnAP2 involved in the phenotype of B. napus, we used a transgenic approach that involved targeted RNA interference (RNAi) repression induced by ihp-RNA. Floral various phenotype defectives and reduced female fertility were observed in B. napus BnAP2-RNAi lines. Loss of the function of BnAP2 gene also resulted in delayed sepal abscission and senescence with the ethylene-independent pathway. In the strong BnAP2-RNAi lines, seeds showed defects in shape, structure and development and larger size. Strong BnAP2-RNAi and wild-type seeds initially did not display a significant difference in morphology at 10 DAF, but the development of BnAP2-RNAi seeds was slower than that of wild type at 20 DAF, and further at 30 DAF, wild-type seeds were essentially at their final size, whereas BnAP2-RNAi seeds stopped growing and developing and gradually withered.

Prevalence and Correlates of Drug/Alcohol-Facilitated and Incapacitated Sexual Assault in a Nationally Representative Sample of Adolescent Girls

ERIC Educational Resources Information Center

McCauley, Jenna L.; Conoscenti, Lauren M.; Ruggiero, Kenneth J.; Resnick, Heidi S.; Saunders, Benjamin E.; Kilpatrick, Dean G.

2009-01-01

Incapacitated/drug-alcohol facilitated sexual assault (IS/DAFS) is rapidly gaining recognition as a distinct form of assault with unique public health implications. This study reports the prevalence, case characteristics, and associated health risks of IS/DAFS using a large, nationally representative sample of 1,763 adolescent girls. Results…

A Proposed Pattern of Enterprise Architecture

DTIC Science & Technology

2013-02-01

consistent architecture descriptions. UPDM comprises extensions to both OMG’s Unified Modelling Language (UML) and Systems Modelling Language ( SysML ...those who use UML and SysML . These represent significant advancements that enable architecture trade-off analyses, architecture model execution...Language ( SysML ), and thus provides for architectural descriptions that contain a rich set of (formally) connected DoDAF/MoDAF viewpoints expressed

Evaluation on simultaneous removal of particles and off-flavors using population balance for application of powdered activated carbon in dissolved air flotation process.

PubMed

Kwak, D H; Yoo, S J; Lee, E J; Lee, J W

2010-01-01

Most of the water treatment plants applying the DAF process are faced with off-flavors control problems. For simultaneous control of particles of impurities and dissolved organics that cause pungent taste and odor in water, an effective method would be the simple application of powdered activated carbon (PAC) in the DAF process. A series of experiments were carried out to explore the feasibility for simultaneous removal of kaolin particles and organic compounds that produce off-flavors (2-MIB and geosmin). In addition, the flotation efficiency of kaolin and PAC particles adsorbing organics in the DAF process was evaluated by employing the population balance theory. The removal efficiency of 2-MIB and geosmin under the treatment condition with kaolin particles for simultaneous treatment was lower than that of the individual treatment. The decrease in the removal efficiency was probably caused by 2-MIB and geosmin remaining in the PAC particle in the treated water of DAF after bubble flotation. Simulation results obtained by the population balance model indicate, that the initial collision-attachment efficiency of PAC particles was lower than that of kaolin particles.

Removal of iron ore slimes from a highly turbid water by DAF.

PubMed

Faustino, L M; Braga, A S; Sacchi, G D; Whitaker, W; Reali, M A P; Leal Filho, L S; Daniel, L A

2018-05-30

This paper addresses Dissolved Air Flotation (DAF) process variables, such as the flocculation parameters and the recycle water addition, as well as the pretreatment chemical variables (coagulation conditions), to determine the optimal values for the flotation of iron ore slimes found in a highly turbid water sample from the Gualaxo do Norte River, a tributary of the Doce River Basin in Minas Gerais, Brazil. This work was conducted using a flotatest batch laboratory-scale device to evaluate the effectiveness of DAF for cleaning the water polluted by the Samarco tailings dam leakage and determine the ability of DAF to reduce the water turbidity from 358 NTU to values below 100 NTU, aiming to comply with current legislation. The results showed that the four types of tested coagulants (PAC, ferric chloride, Tanfloc SG and Tanfloc SL) provided adequate conditions for coagulation, flocculation and flotation (in the range of 90-99.6% turbidity reduction). Although the process variables were optimized and low residual turbidity vales were achieved, results revealed that a portion of the flocs settled at the bottom of the flotatest columns, which indicated that the turbidity results represented removal caused by a combination of flotation and sedimentation processes simultaneously.

Transcriptomic analysis revealed the mechanism of oil dynamic accumulation during developing Siberian apricot (Prunus sibirica L.) seed kernels for the development of woody biodiesel.

PubMed

Niu, Jun; An, Jiyong; Wang, Libing; Fang, Chengliang; Ha, Denglong; Fu, Chengyu; Qiu, Lin; Yu, Haiyan; Zhao, Haiyan; Hou, Xinyu; Xiang, Zheng; Zhou, Sufan; Zhang, Zhixiang; Feng, Xinyi; Lin, Shanzhi

2015-01-01

Siberian apricot (Prunus sibirica L.) has emerged as a novel potential source of biodiesel in China, but the molecular regulatory mechanism of oil accumulation in Siberian apricot seed kernels (SASK) is still unknown at present. To better develop SASK oil as woody biodiesel, it is essential to profile transcriptome and to identify the full repertoire of potential unigenes involved in the formation and accumulation of oil SASK during the different developing stages. We firstly detected the temporal patterns for oil content and fatty acid (FA) compositions of SASK in 7 different developing stages. The best time for obtaining the high quality and quantity of SASK oil was characterized at 60 days after flowering (DAF), and the representative periods (10, 30, 50, 60, and 70 DAF) were selected for transcriptomic analysis. By Illumina/Solexa sequencings, approximately 65 million short reads (average length = 96 bp) were obtained, and then assembled into 124,070 unigenes by Trinity strategy (mean size = 829.62 bp). A total of 3,000, 2,781, 2,620, and 2,675 differentially expressed unigenes were identified at 30, 50, 60, and 70 DAF (10 DAF as the control) by DESeq method, respectively. The relationship between the unigene transcriptional profiles and the oil dynamic patterns in developing SASK was comparatively analyzed, and the specific unigenes encoding some known enzymes and transcription factors involved in acetyl-coenzyme A (acetyl-CoA) formation and oil accumulation were determined. Additionally, 5 key metabolic genes implicated in SASK oil accumulation were experimentally validated by quantitative real-time PCR (qRT-PCR). Our findings could help to construction of oil accumulated pathway and to elucidate the molecular regulatory mechanism of increased oil production in developing SASK. This is the first study of oil temporal patterns, transcriptome sequencings, and differential profiles in developing SASK. All our results will serve as the important foundation to further deeply explore the regulatory mechanism of SASK high-quality oil accumulation, and may also provide some reference for researching the woody biodiesel plants.

Synthesis of new C-25 and C-26 steroidal acids as potential ligands of the nuclear receptors DAF-12, LXR and GR.

PubMed

Dansey, María V; Del Fueyo, María C; Veleiro, Adriana S; Di Chenna, Pablo H

2017-05-01

A new methodology to obtain C-25 and C-26 steroidal acids starting from pregnenolone is described. Construction of the side chain was achieved by applying the Mukaiyama aldol reaction with a non-hydrolytic work-up to isolate the trapped silyl enol ether with higher yields. Using this methodology we synthesized three new steroidal acids as potential ligands of DAF-12, Liver X and Glucocorticoid nuclear receptors and studied their activity in reporter gene assays. Our results show that replacement of the 21-CH 3 by a 20-keto group in the side chains of the cholestane scaffold of DAF-12 or Liver X receptors ligands causes the loss of the activity. Copyright © 2017 Elsevier Inc. All rights reserved.

Natural lignans from Arctium lappa as antiaging agents in Caenorhabditis elegans.

PubMed

Su, Shan; Wink, Michael

2015-09-01

Arctium lappa is a well-known traditional medicinal plant in China (TCM) and Europe that has been used for thousands of years to treat arthritis, baldness or cancer. The plant produces lignans as secondary metabolites, which have a wide range of bioactivities. Yet, their antiaging potential has not been explored. In this study, we isolated six lignans from A. lappa seeds, namely arctigenin, matairesinol, arctiin, (iso)lappaol A, lappaol C, and lappaol F. The antioxidant and antiaging properties of the isolated lignans were studied using Caenorhabditis elegans as a relevant animal model. All lignans at concentrations of 10 and 100 μM significantly extended the mean life span of C. elegans. The strongest effect was observed with matairesinol, which at a concentration of 100 μM extended the life span of worms by 25%. Additionally, we observed that five lignans are strong free radical-scavengers in vitro and in vivo and all lignans can improve survival of C. elegans under oxidative stress. Furthermore, the lignans can induce the nuclear translocation of the transcription factor DAF-16 and up-regulate its expression, suggesting that a possible underlying mechanism of the observed longevity-promoting activity of lignans depends on DAF-16 mediated signaling pathway. All lignans up-regulated the expression of jnk-1, indicating that lignans may promote the C. elegans longevity and stress resistance through a JNK-1-DAF-16 cascade. Our study reports new antiaging activities of lignans, which might be candidates for developing antiaging agents. Copyright © 2015 Elsevier Ltd. All rights reserved.

Therapeutic inhibition of the complement system. Y2K update.

PubMed

Asghar, S S; Pasch, M C

2000-09-01

Activation of complement is an essential part of the mechanism of pathogenesis of a large number of human diseases; its inhibition by pharmacological means is likely to suppress disease processes in complement mediated diseases. From this point of view low molecular weight synthetic inhibitors of complement are being developed and high molecular weight natural inhibitors of human origin present in plasma or embedded in cell membrane are being purified or produced in their recombinant forms. This review is concerned with high molecular weight inhibitors, some of which are already in clinical use but may be efficacious in many other diseases in which they have not yet been tried. C1-esterase inhibitor (C1-INH) concentrate prepared from human plasma is being successfully used for the treatment of hereditary angioneurotic edema. Recently, C1-INH has been found to be consumed in severe inflammation and has been shown to exert beneficial effects in several inflammatory conditions such as human sepsis, post-operative myocardial dysfunction due to reperfusion injury, severe capillary leakage syndrome after bone marrow transplantation, reperfusion injury after lung transplantation, burn, and cytotoxicity caused by IL-2 therapy in cancer. Factor I has been used for the treatment of factor I deficiency. Recombinant soluble forms of membrane cofactor protein (MCP), and decay accelerating factor (DAF) have not yet been tried in humans but have been shown to be effective in immune complex mediate inflammation in animals. Organs of pigs transgenic for one or more of human membrane regulators of complement namely membrane cofactor protein (MCP), decay accelerating factor (DAF) or CD59, are being produced for transplantation into humans. They have been shown to be resistant to hyperacute rejection in non-human primates; acute vascular rejection is still a problem in their clinical use. It is hoped that these observations together with future developments will make xeno-transplantation in clinical practice a reality. Several recombinant variants of complement receptor 1 (CR1) have been produced. The most effective of these appears to be sCR1-SLe x, sCR1 part of which inhibits complement and carbohydrate Sle x moiety inhibits selectin mediated interactions of neutrophils and lymphocytes with endothelium. Although clinical trials of sCR1 in humans is eagerly awaited, several of the recombinant versions of sCR1 have been shown to suppress ischemia/reperfusion injury, thermal trauma, and immune complex mediated inflammation. They have also been shown to be effective in experimental models of systemic sclerosis, arthritis, myasthenia gravis, Guillain Barré syndrome and glomerulonephritis. Intravenous immunoglobulin, three of the most prominent properties of which are neutralization of autoantibody activity, suppression of autoantibody production and inhibition of complement activity, is being used in several diseases. These include autoimmune thrombocyopenic purpura, Kawasaki disease and several neurological diseases such as myasthenia gravis and Guillain Barre syndrome. In many uncontrolled small scale studies intravenous immunoglobulin has been shown to be effective in many immunological including dermatological diseases; controlled clinical trials in a large number of patients with these diseases is needed to establish the efficacy. It is hoped that in future therapeutic inhibition of complement will be one of the major approaches to combat many human diseases.

The Caenorhabditis elegans DAF-12 nuclear receptor: structure, dynamics, and interaction with ligands.

PubMed

Alvarez, Lautaro D; Mañez, Pau Arroyo; Estrin, Darío A; Burton, Gerardo

2012-07-01

A structure for the ligand binding domain (LBD) of the DAF-12 receptor from Caenorhabditis elegans was obtained from the X-ray crystal structure of the receptor LBD from Strongyloides stercoralis bound to (25R)-Δ(7)-dafachronic acid (DA) (pdb:3GYU). The model was constructed in the presence of the ligand using a combination of Modeller, Autodock, and molecular dynamics (MD) programs, and then its dynamical behavior was studied by MD. A strong ligand binding mode (LBM) was found, with the three arginines in the ligand binding pocket (LBP) contacting the C-26 carboxylate group of the DA. The quality of the ceDAF-12 model was then evaluated by constructing several ligand systems for which the experimental activity is known. Thus, the dynamical behavior of the ceDAF-12 complex with the more active (25S)-Δ(7)-DA showed two distinct binding modes, one of them being energetically more favorable compared with the 25R isomer. Then the effect of the Arg564Cys and Arg598Met mutations on the (25R)-Δ(7)-DA binding was analyzed. The MD simulations showed that in the first case the complex was unstable, consistent with the lack of transactivation activity of (25R)-Δ(7)-DA in this mutant. Instead, in the case of the Arg598Met mutant, known to produce a partial loss of activity, our model predicted smaller effects on the LBM with a more stable MD trajectory. The model also showed that removal of the C-25 methyl does not impede the simultaneous strong interaction of the carboxylate with the three arginines, predicting that 27-nor-DAs are putative ceDAF-12 ligands. Copyright © 2012 Wiley Periodicals, Inc.

Lamella dissolved air flotation treatment of fish farming effluents as a part of an integrated farming and effluent treatment concept.

PubMed

Jokela, Petri; Lepistö, Raghida

2014-01-01

Nutrient emissions from fish farming can be reduced by a bag pen, i.e., a floating circular basin which serves simultaneously both as a fish cultivation tank and a swirl separation tank. Solid matter (excreta and uneaten feed) is collected at the bottom of the bag pen and pumped as an underflow to a dissolved air flotation (DAF) unit for nutrient removal. DAF equipped with lamella elements was studied in real conditions. Altogether 3000 rainbow trout females (2.0 kg each) were cultivated. Solid-water mixture was pumped from the bottom of the bag pen to an equalizing basin using a sequence of 2-min pumping followed by a 4-min pause. In some tests the influent was pumped directly and continuously from the bag pen to DAF. The influent quality changed substantially: average suspended solids (SS) and phosphorus (P) concentrations were 290 mg l⁻¹ ± 110 mg l⁻¹ and 3.2 mg l⁻¹ ± 1.2 mg l⁻¹, respectively. When the influent was fresh and P strongly associated with SS, DAF without precipitation chemicals produced up to 86% SS and 83% P removals. The influence of chemical doses was studied using 6.4-29.2 mg Fe l⁻¹ with hydraulic loadings (HLs) of 11.0-11.7 m h⁻¹. SS and P removal did not change substantially and the effluent concentration levelled at 30 mg SS l⁻¹ and 0.20-0.30 mg P l⁻¹, respectively. The lamella DAF, coupled with ferric precipitation, produced up to 90% P and 80% nitrogen reductions. HLs, excluding recycle water flow and lamella projection, up to 21 m h⁻¹ could be used.

Key Issues in the Application of Knowledge Management in Education

DTIC Science & Technology

2005-03-01

designed instructional programs are often outdated before they ever leave the design stage (DAF, 1994; DAF, 1993). Such programs are far too rigid...and end up drowning in raw facts and figures (Davenport, Harris, De Long & Jacobson, 2001). Information When relevance or context is applied to...of data to information can be categorized five ways (Davenport & Prusak, 1998; Davenport, Harris, De Long & Jacobson, 2001). 1. Contexualized

Timing mechanism and effective activation energy concerned with aging and lifespan in the long-lived and thermosensory mutants of Caenorhabditis elegans.

PubMed

Suda, Hitoshi; Sato, Kazuya; Yanase, Sumino

2012-01-01

The lifespans of many poikilothermic animals, including the nematode Caenorhabditis elegans, depend significantly on environmental temperature. Using long-living, thermosensory mutants of C. elegans, we tested whether the temperature dependency of the mean lifespan is compatible with the Arrhenius equation, which typically represents one of the chemical reaction rate theories. The temperature dependency of C. elegans was the Arrhenius type or normal, but daf-2(e1370) mutants were quite different from the others. However, taking into account the effect of the thermal denaturation of DAF-2 with the temperature, we showed that our analyzed results are compatible with previous ones. We investigated the timing mechanism of one parameter (the onset of biodemographic aging (t(0))) in the lifespan equation by applying the RNAi feeding method to daf-2 mutants in order to suppress daf-16 activity at different times during the life cycle. In summary, we further deepened the biological role of two elements, t(0) and z (the inverse of the aging rate), in the lifespan equation and mean lifespan formulated by our diffusion model z(2) = 4Dt(0), where z is composed of t(0) and D (the diffusion constant). Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Removal of Anabaena flos-aquae in water treatment process using Moringa oleifera and assessment of fatty acid profile of generated sludge.

PubMed

Moreti, Livia O R; Coldebella, Priscila Ferri; Camacho, Franciele P; Carvalho Bongiovani, Milene; Pereira de Souza, Aloisio Henrique; Kirie Gohara, Aline; Matsushita, Makoto; Fernandes Silva, Marcela; Nishi, Letícia; Bergamasco, Rosângela

2016-01-01

This study aimed to evaluate the efficiency of the coagulation/flocculation/dissolved air flotation (C/F/DAF) process using the coagulant Moringa oleifera (MO) seed powder, and to analyse the profile of fatty acids present in the generated sludge after treatment. For the tests, deionized water artificially contaminated with cell cultures of Anabaena flos-aquae was used, with a cell density in the order of 10(4) cells mL(-1). C/F/DAF tests were conducted using 'Flotest' equipment. For fatty acid profile analyses, a gas chromatograph equipped with a flame ionization detector was used. It was seen that the optimal dosage (100 mg L(-1)) of MO used in the C/F/DAF process was efficient at removing nearly all A. flos-aquae cells (96.4%). The sludge obtained after treatment contained oleic acid (61.7%) and palmitic acid (10.8%). Thus, a water treatment process using C/F/DAF linked to integral MO powder seed was found to be efficient in removing cells of cyanobacteria, and produced a sludge rich in oleic acid that is a precursor favourable for obtaining quality biodiesel, thus becoming an alternative application for the recycling of such biomass.

Critical evaluation and modeling of algal harvesting using dissolved air flotation. DAF Algal Harvesting Modeling

DOE PAGES

Zhang, Xuezhi; Hewson, John C.; Amendola, Pasquale; ...

2014-07-14

In our study, Chlorella zofingiensis harvesting by dissolved air flotation (DAF) was critically evaluated with regard to algal concentration, culture conditions, type and dosage of coagulants, and recycle ratio. Harvesting efficiency increased with coagulant dosage and leveled off at 81%, 86%, 91%, and 87% when chitosan, Al 3+, Fe 3+, and cetyl trimethylammonium bromide (CTAB) were used at dosages of 70, 180, 250, and 500 mg g -1, respectively. The DAF efficiency-coagulant dosage relationship changed with algal culture conditions. In evaluating the influence of the initial algal concentration and recycle ratio revealed that, under conditions typical for algal harvesting, wemore » found that it is possible that the number of bubbles is insufficient. A DAF algal harvesting model was developed to explain this observation by introducing mass-based floc size distributions and a bubble limitation into the white water blanket model. Moreover, the model revealed the importance of coagulation to increase floc-bubble collision and attachment, and the preferential interaction of bubbles with larger flocs, which limited the availability of bubbles to the smaller sized flocs. The harvesting efficiencies predicted by the model agree reasonably with experimental data obtained at different Al 3+ dosages, algal concentrations, and recycle ratios. Based on this modeling, critical parameters for efficient algal harvesting were identified.« less

Kinematic Analysis of Speech Sound Sequencing Errors Induced by Delayed Auditory Feedback.

PubMed

Cler, Gabriel J; Lee, Jackson C; Mittelman, Talia; Stepp, Cara E; Bohland, Jason W

2017-06-22

Delayed auditory feedback (DAF) causes speakers to become disfluent and make phonological errors. Methods for assessing the kinematics of speech errors are lacking, with most DAF studies relying on auditory perceptual analyses, which may be problematic, as errors judged to be categorical may actually represent blends of sounds or articulatory errors. Eight typical speakers produced nonsense syllable sequences under normal and DAF (200 ms). Lip and tongue kinematics were captured with electromagnetic articulography. Time-locked acoustic recordings were transcribed, and the kinematics of utterances with and without perceived errors were analyzed with existing and novel quantitative methods. New multivariate measures showed that for 5 participants, kinematic variability for productions perceived to be error free was significantly increased under delay; these results were validated by using the spatiotemporal index measure. Analysis of error trials revealed both typical productions of a nontarget syllable and productions with articulatory kinematics that incorporated aspects of both the target and the perceived utterance. This study is among the first to characterize articulatory changes under DAF and provides evidence for different classes of speech errors, which may not be perceptually salient. New methods were developed that may aid visualization and analysis of large kinematic data sets. https://doi.org/10.23641/asha.5103067.

Kinematic Analysis of Speech Sound Sequencing Errors Induced by Delayed Auditory Feedback

PubMed Central

Lee, Jackson C.; Mittelman, Talia; Stepp, Cara E.; Bohland, Jason W.

2017-01-01

Purpose Delayed auditory feedback (DAF) causes speakers to become disfluent and make phonological errors. Methods for assessing the kinematics of speech errors are lacking, with most DAF studies relying on auditory perceptual analyses, which may be problematic, as errors judged to be categorical may actually represent blends of sounds or articulatory errors. Method Eight typical speakers produced nonsense syllable sequences under normal and DAF (200 ms). Lip and tongue kinematics were captured with electromagnetic articulography. Time-locked acoustic recordings were transcribed, and the kinematics of utterances with and without perceived errors were analyzed with existing and novel quantitative methods. Results New multivariate measures showed that for 5 participants, kinematic variability for productions perceived to be error free was significantly increased under delay; these results were validated by using the spatiotemporal index measure. Analysis of error trials revealed both typical productions of a nontarget syllable and productions with articulatory kinematics that incorporated aspects of both the target and the perceived utterance. Conclusions This study is among the first to characterize articulatory changes under DAF and provides evidence for different classes of speech errors, which may not be perceptually salient. New methods were developed that may aid visualization and analysis of large kinematic data sets. Supplemental Material https://doi.org/10.23641/asha.5103067 PMID:28655038

Critical evaluation and modeling of algal harvesting using dissolved air flotation. DAF Algal Harvesting Modeling

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

Zhang, Xuezhi; Hewson, John C.; Amendola, Pasquale

In our study, Chlorella zofingiensis harvesting by dissolved air flotation (DAF) was critically evaluated with regard to algal concentration, culture conditions, type and dosage of coagulants, and recycle ratio. Harvesting efficiency increased with coagulant dosage and leveled off at 81%, 86%, 91%, and 87% when chitosan, Al 3+, Fe 3+, and cetyl trimethylammonium bromide (CTAB) were used at dosages of 70, 180, 250, and 500 mg g -1, respectively. The DAF efficiency-coagulant dosage relationship changed with algal culture conditions. In evaluating the influence of the initial algal concentration and recycle ratio revealed that, under conditions typical for algal harvesting, wemore » found that it is possible that the number of bubbles is insufficient. A DAF algal harvesting model was developed to explain this observation by introducing mass-based floc size distributions and a bubble limitation into the white water blanket model. Moreover, the model revealed the importance of coagulation to increase floc-bubble collision and attachment, and the preferential interaction of bubbles with larger flocs, which limited the availability of bubbles to the smaller sized flocs. The harvesting efficiencies predicted by the model agree reasonably with experimental data obtained at different Al 3+ dosages, algal concentrations, and recycle ratios. Based on this modeling, critical parameters for efficient algal harvesting were identified.« less

Landslide Mobility and Hazards: A Geophysical Overview of the Oso Disaster

NASA Astrophysics Data System (ADS)

Iverson, R. M.; George, D. L.; Allstadt, K.; Godt, J.; Reid, M. E.; Vallance, J. W.; Schilling, S. P.; Cannon, C.; Magirl, C. S.; Collins, B. D.; Baum, R. L.; Coe, J. A.; Schulz, W. H.; Bower, J. B.

2014-12-01

Some landslides move slowly or intermittently downslope, whereas others accelerate catastrophically and run out long distances across flat or gently sloping terrain. Seldom does landsliding of one type transition abruptly into the other, however, and seldom are the consequences more severe than at a site near Oso, Washington, where more than 40 fatalities resulted from a high-speed, long-runout landslide on 22 March 2014. Our interpretations of seismic data inversions and eyewitness accounts indicate that the Oso event began gradually, with remobilization of old landslide deposits that were unusually wet due to months of exceptional precipitation. For about 50 s, relatively slow downslope motion of these deposits withdrew support from a bluff above them, and then the bluff collapsed abruptly. This collapse radiated strong broadband seismic energy and rapidly loaded the old landslide material downslope. We infer that this rapid loading of previously dilated landslide debris caused contractive deformation, widespread liquefaction, and runaway acceleration. The resulting debris avalanche flow (DAF) had a volume of 8 ×106 m3and a fahrböschung (H/L ratio) of 0.106, making it exceptionally mobile for a landslide of its size. The leading edge of the Oso DAF may have gained mobility by entraining water as it displaced the adjacent Stillaguamish River and by liquefying wet floodplain sediments as it overran them, and it formed distal deposits that resembled those of many wood-freighted debris flows. The transition from relatively slow landslide motion (which had occurred intermittently for decades at the Oso site) to high-speed motion and long runout appears to have been very sensitive to contingencies. Our simulations of the Oso event using a new numerical model (D-Claw) show that small differences in water-saturated porosity (n) were sufficient to cause divergent landslide behaviors. In a case with n = 0.38, D-Claw predicts runaway liquefaction and high-speed runout much like that observed at Oso, and in a case with n = 0.36, it predicts much slower landsliding that ceases after only about 100 m of motion. This behavioral bifurcation has fundamental physical importance as well as large ramifications for assessment of landslide hazards.

Blockmodeling and the Estimation of Evolutionary Architectural Growth in Major Defense Acquisition Programs

DTIC Science & Technology

2016-04-30

Dabkowski, and Dixit (2015), we demonstrate that the DoDAF models required pre–MS A map to 14 of the 18 parameters of the Constructive Systems...engineering effort in complex systems. Saarbrücken, Germany: VDM Verlag. Valerdi, R., Dabkowski, M., & Dixit , I. (2015). Reliability improvement of...R., Dabkowski, M., & Dixit , I. (2015). Reliability Improvement of Major Defense Acquisition Program Cost Estimates – Mapping DoDAF to COSYSMO

Effects of Lactobacillus salivarius, Lactobacillus reuteri, and Pediococcus acidilactici on the nematode Caenorhabditis elegans include possible antitumor activity.

PubMed

Fasseas, Michael K; Fasseas, Costas; Mountzouris, Konstantinos C; Syntichaki, Popi

2013-03-01

This study examined the effects of three lactic acid bacteria (LAB) strains on the nematode Caenorhabditis elegans. Lactobacillus salivarius, Lactobacillus reuteri, and Pediococcus acidilactici were found to inhibit the development and growth of the worm. Compared to Escherichia coli used as the control, L. reuteri and P. acidilactici reduced the lifespan of wild-type and short-lived daf-16 worms. On the contrary, L. salivarius extended the lifespan of daf-16 worms when used live, but reduced it as UV-killed bacteria. The three LAB induced the expression of genes involved in pathogen response and inhibited the growth of tumor-like germ cells, without affecting DAF16 localization or increasing corpse cells. Our results suggest the possible use of C. elegans as a model for studying the antitumor attributes of LAB. The negative effects of these LAB strains on the nematode also indicate their potential use against parasitic nematodes.

Effect of delayed auditory feedback on normal speakers at two speech rates

NASA Astrophysics Data System (ADS)

Stuart, Andrew; Kalinowski, Joseph; Rastatter, Michael P.; Lynch, Kerry

2002-05-01

This study investigated the effect of short and long auditory feedback delays at two speech rates with normal speakers. Seventeen participants spoke under delayed auditory feedback (DAF) at 0, 25, 50, and 200 ms at normal and fast rates of speech. Significantly two to three times more dysfluencies were displayed at 200 ms (p<0.05) relative to no delay or the shorter delays. There were significantly more dysfluencies observed at the fast rate of speech (p=0.028). These findings implicate the peripheral feedback system(s) of fluent speakers for the disruptive effects of DAF on normal speech production at long auditory feedback delays. Considering the contrast in fluency/dysfluency exhibited between normal speakers and those who stutter at short and long delays, it appears that speech disruption of normal speakers under DAF is a poor analog of stuttering.

Transcriptome Analysis of Genes Involved in Lipid Biosynthesis in the Developing Embryo of Pecan (Carya illinoinensis).

PubMed

Huang, Ruimin; Huang, Youjun; Sun, Zhichao; Huang, Jianqin; Wang, Zhengjia

2017-05-24

Pecan (Carya illinoinensis) is an important woody tree species because of the high content of healthy oil in its nut. Thus far, the pathways and key genes related to oil biosynthesis in developing pecan seeds remain largely unclear. Our analyses revealed that mature pecan embryo accumulated more than 80% oil, in which 90% was unsaturated fatty acids with abundant oleic acid. RNA sequencing generated 84,643 unigenes in three cDNA libraries prepared from pecan embryos collected at 105, 120, and 165 days after flowering (DAF). We identified 153 unigenes associated with lipid biosynthesis, including 107 unigenes for fatty acid biosynthesis, 34 for triacylglycerol biosynthesis, 7 for oil bodies, and 5 for transcription factors involved in oil synthesis. The genes associated with fatty acid synthesis were the most abundantly expressed genes at 120 DAF. Additionally, the biosynthesis of oil began to increase while crude fat contents increased from 16.61 to 74.45% (165 DAF). We identified four SAD, two FAD2, one FAD6, two FAD7, and two FAD8 unigenes responsible for unsaturated fatty acid biosynthesis. However, FAD3 homologues were not detected. Consequently, we inferred that the linolenic acid in developing pecan embryos is generated by FAD7 and FAD8 in plastids rather than FAD3 in endoplasmic reticula. During pecan embryo development, different unigenes are expressed for plastidial and cytosolic glycolysis. Plastidial glycolysis is more relevant to lipid synthesis than cytosolic glycolysis. The 18 most important genes associated with lipid biosynthesis were evaluated in five stages of developing embryos using quantitative PCR (qPCR). The qPCR data were well consistent with their expression in transcriptomic analyses. Our data would be important for the metabolic engineering of pecans to increase oil contents and modify fatty acid composition.

Evaluation of the Fluids Mixing Enclosure System for Life Science Experiments During a Commercial Caenorhabditis elegans Spaceflight Experiment.

PubMed

Warren, Paul; Golden, Andy; Hanover, John; Love, Dona; Shephard, Freya; Szewczyk, Nathaniel J

2013-06-01

The Student Spaceflight Experiments Program (SSEP) is a United States national science, technology, engineering, and mathematics initiative that aims to increase student interest in science by offering opportunities to perform spaceflight experiments. The experiment detailed here was selected and flown aboard the third SSEP mission and the first SSEP mission to the International Space Station (ISS). Caenorhabditis elegans is a small, transparent, self-fertilizing hermaphroditic roundworm that is commonly used in biological experiments both on Earth and in Low Earth Orbit. Past experiments have found decreased expression of mRNA for several genes whose expression can be controlled by the FOXO transcription factor DAF-16. We flew a daf-16 mutant and control worms to determine if the effects of spaceflight on C. elegans are mediated by DAF-16. The experiment used a Type Two Fluids Mixing Enclosure (FME), developed by Nanoracks LLC, and was delivered to the ISS aboard the SpaceX Dragon and returned aboard the Russian Soyuz. The short time interval between experiment selection and the flight rendered preflight experiment verification tests impossible. In addition, published research regarding the viability of the FME in life science experiments was not available. The experiment was therefore structured in such a way as to gather the needed data. Here we report that C. elegans can survive relatively short storage and activation in the FME but cannot produce viable populations for post-flight analysis on extended missions. The FME appears to support short-duration life science experiments, potentially on supply or crew exchange missions, but not on longer ISS expeditions. Additionally, the flown FME was not properly activated, reportedly due to a flaw in training procedures. We suggest that a modified transparent FME could prevent similar failures in future flight experiments.

Evaluation of the fluids mixing enclosure system for life science experiments during a commercial Caenorhabditis elegans spaceflight experiment

NASA Astrophysics Data System (ADS)

Warren, Paul; Golden, Andy; Hanover, John; Love, Dona; Shephard, Freya; Szewczyk, Nathaniel J.

2013-06-01

The Student Spaceflight Experiments Program (SSEP) is a United States national science, technology, engineering, and mathematics initiative that aims to increase student interest in science by offering opportunities to perform spaceflight experiments. The experiment detailed here was selected and flown aboard the third SSEP mission and the first SSEP mission to the International Space Station (ISS). Caenorhabditis elegans is a small, transparent, self-fertilizing hermaphroditic roundworm that is commonly used in biological experiments both on Earth and in Low Earth Orbit. Past experiments have found decreased expression of mRNA for several genes whose expression can be controlled by the FOXO transcription factor DAF-16. We flew a daf-16 mutant and control worms to determine if the effects of spaceflight on C. elegans are mediated by DAF-16. The experiment used a Type Two Fluids Mixing Enclosure (FME), developed by Nanoracks LLC, and was delivered to the ISS aboard the SpaceX Dragon and returned aboard the Russian Soyuz. The short time interval between experiment selection and the flight rendered preflight experiment verification tests impossible. In addition, published research regarding the viability of the FME in life science experiments was not available. The experiment was therefore structured in such a way as to gather the needed data. Here we report that C. elegans can survive relatively short storage and activation in the FME but cannot produce viable populations for post-flight analysis on extended missions. The FME appears to support short-duration life science experiments, potentially on supply or crew exchange missions, but not on longer ISS expeditions. Additionally, the flown FME was not properly activated, reportedly due to a flaw in training procedures. We suggest that a modified transparent FME could prevent similar failures in future flight experiments.

Evaluation of the Fluids Mixing Enclosure System for Life Science Experiments During a Commercial Caenorhabditis elegans Spaceflight Experiment

PubMed Central

Warren, Paul; Golden, Andy; Hanover, John; Love, Dona; Shephard, Freya; Szewczyk, Nathaniel J.

2013-01-01

The Student Spaceflight Experiments Program (SSEP) is a United States national science, technology, engineering, and mathematics initiative that aims to increase student interest in science by offering opportunities to perform spaceflight experiments. The experiment detailed here was selected and flown aboard the third SSEP mission and the first SSEP mission to the International Space Station (ISS). Caenorhabditis elegans is a small, transparent, self-fertilizing hermaphroditic roundworm that is commonly used in biological experiments both on Earth and in Low Earth Orbit. Past experiments have found decreased expression of mRNA for several genes whose expression can be controlled by the FOXO transcription factor DAF-16. We flew a daf-16 mutant and control worms to determine if the effects of spaceflight on C. elegans are mediated by DAF-16. The experiment used a Type Two Fluids Mixing Enclosure (FME), developed by Nanoracks LLC, and was delivered to the ISS aboard the SpaceX Dragon and returned aboard the Russian Soyuz. The short time interval between experiment selection and the flight rendered preflight experiment verification tests impossible. In addition, published research regarding the viability of the FME in life science experiments was not available. The experiment was therefore structured in such a way as to gather the needed data. Here we report that C. elegans can survive relatively short storage and activation in the FME but cannot produce viable populations for post-flight analysis on extended missions. The FME appears to support short-duration life science experiments, potentially on supply or crew exchange missions, but not on longer ISS expeditions. Additionally, the flown FME was not properly activated, reportedly due to a flaw in training procedures. We suggest that a modified transparent FME could prevent similar failures in future flight experiments. PMID:23794777

A pilot plant study using conventional and advanced water treatment processes: Evaluating removal efficiency of indicator compounds representative of pharmaceuticals and personal care products.

PubMed

Zhang, Shuangyi; Gitungo, Stephen; Axe, Lisa; Dyksen, John E; Raczko, Robert F

2016-11-15

With widespread occurrence of pharmaceuticals and personal care products (PPCPs) in the water cycle, their presence in source water has led to the need to better understand their treatability and removal efficiency in treatment processes. Fifteen indicator compounds were identified to represent the large number of PPCPs reported worldwide. Criteria applied to determine the indicator compounds included PPCPs widely used, observed at great frequency in aqueous systems, resistant to treatment, persistent in the environment, and representative of classes of organics. Through a pilot plant investigation to understand the optimal combination of unit process for treating PPCPs, 12 treatment trains with their additive and synergistic contributions were investigated; processes included dissolved air flotation (DAF), pre- and intermediate-ozonation with and without H 2 O 2 , intermediate chlorination, dual media filtration, granular activated carbon (GAC), and UV/H 2 O 2 . Treatment trains that achieved the greatest removals involved 1. DAF followed by intermediate ozonation, dual media filtration, and virgin GAC; 2. pre-ozonation followed by DAF, dual media filtration, and virgin GAC; and, 3. DAF (with either pre- or intermediate oxidation) followed by dual media filtration and UV/H 2 O 2 . Results revealed significant removal efficiencies for virgin GAC (preceded by DAF and intermediate ozonation) and UV/H 2 O 2 with an intensity of 700 mJ/cm 2 , where more than 12 of the compounds were removed by greater than 90%. Reduced PPCP removals were observed with virgin GAC preceded by pre-ozonation and DAF. Intermediate ozonation was more effective than using pre-ozonation, demonstrating the importance of this process targeting PPCPs after treatment of natural organic matter. Removal efficiencies of indicator compounds through ozonation were found to be a function of the O 3 rate constants (k O3 ). For compounds with low O 3 rate constants (k O3  < 10 M -1 s -1 ), H 2 O 2 addition in the O 3 reactor was required. Of the 15 indicator compounds, tri(2-chloroethyl) phosphate (TCEP) and cotinine were observed to be the most recalcitrant. Although UV/H 2 O 2 with elevated intensity (700 mJ/cm 2 ) was effective for PPCP removals, energy requirements far exceed intensities applied for disinfection. Copyright © 2016 Elsevier Ltd. All rights reserved.

Implications for Arms Control in Technology Transfer to Less Developed Countries (LDC’s). Volume I. Considerations in Controlling Dual-Use Technology Products: An Overview

DTIC Science & Technology

1980-09-01

Mitsubishi Brazil - Mercedes - Benz FranceNetherlands - DAF France - Hispani-Suiza, Sweden - Volvo-Penta SOFAM, Peugeot West Germany - Motor-Turbinen...Mitsubishi Brazil - Mercedes - Benz Netherlands - DAF France - Hispani-Suiza, Sweden - Volvo-Penta SOFAM, Peugeot West Germany - Motor-Turbinen... marketing practices as later described in pages 4-11. This paper examines likely LDC reactions to a situation in which for whatever reason they are

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

PubMed

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.

Generation of sequence signatures from DNA amplification fingerprints with mini-hairpin and microsatellite primers.

PubMed

Caetano-Anollés, G; Gresshoff, P M

1996-06-01

DNA amplification fingerprinting (DAF) with mini-hairpins harboring arbitrary "core" sequences at their 3' termini were used to fingerprint a variety of templates, including PCR products and whole genomes, to establish genetic relationships between plant tax at the interspecific and intraspecific level, and to identify closely related fungal isolates and plant accessions. No correlation was observed between the sequence of the arbitrary core, the stability of the mini-hairpin structure and DAF efficiency. Mini-hairpin primers with short arbitrary cores and primers complementary to simple sequence repeats present in microsatellites were also used to generate arbitrary signatures from amplification profiles (ASAP). The ASAP strategy is a dual-step amplification procedure that uses at least one primer in each fingerprinting stage. ASAP was able to reproducibly amplify DAF products (representing about 10-15 kb of sequence) following careful optimization of amplification parameters such as primer and template concentration. Avoidance of primer sequences partially complementary to DAF product termini was necessary in order to produce distinct fingerprints. This allowed the combinatorial use of oligomers in nucleic acid screening, with numerous ASAP fingerprinting reactions based on a limited number of primer sequences. Mini-hairpin primers and ASAP analysis significantly increased detection of polymorphic DNA, separating closely related bermudagrass (Cynodon) cultivars and detecting putatively linked markers in bulked segregant analysis of the soybean (Glycine max) supernodulation (nitrate-tolerant symbiosis) locus.

Performance testing of a 50 kW VAWT in a built-up environment

NASA Technical Reports Server (NTRS)

Schienbein, L. A.

1981-01-01

The results of performance tests of a DAF Indal 50 kW vertical axis wind turbine are presented. Results of limited free stream turbulence and vertical wind shear measurements at the site are also presented. The close agreement between measured and predicted energy outputs, required to verify the wind turbine power output performance relationship, was not attained. A discussion is presented of factors that may have contributed to the lack of better agreement.

Investigation of the Low Power Stage of an 1178 nm Raman System

DTIC Science & Technology

2013-12-23

LEANNE HENRY, DR-III, DAF KENTON T. WOOD, DR-IV, DAF Work Unit Manager Chief, Laser Division This report is published in the...and 1069 nm pumped Raman laser system where the second Stokes is amplified in a 1121 nm resonator defined by high reflector fiber Bragg gratings (FBGs...the gratings was found to impact the performance of the laser and needs to be dealt with in order to obtain high 1178 nm output power levels. In order

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

DOE PAGES

Dhondt, Ineke; Petyuk, Vladislav A.; Cai, Huaihan; ...

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. But, 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. We found that this slowdown wasmore » most prominent for translation-related and mitochondrial proteins. Conversely, 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.« less

Development of the Potential for Cyanogenesis in Maturing Black Cherry (Prunus serotina Ehrh.) Fruits 1

PubMed Central

Swain, Elisabeth; Li, Chun Ping; Poulton, Jonathan E.

1992-01-01

Biochemical changes related to cyanogenesis (hydrogen cyanide production) were monitored during maturation of black cherry (Prunus serotina Ehrh.) fruits. At weekly intervals from flowering until maturity, fruits (or selected parts thereof) were analyzed for (a) fresh and dry weights, (b) prunasin and amygdalin levels, and (c) levels of the catabolic enzymes amygdalin hydrolase, prunasin hydrolase, and mandelonitrile lyase. During phase I (0-28 days after flowering [DAF]), immature fruits accumulated prunasin (mean: 3 micromoles/fruit) but were acyanogenic because they lacked the above enzymes. Concomitant with cotyledon development during mid-phase II, the seeds began accumulating both amygdalin (mean: 3 micromoles/seed) and the catabolic enzymes and were highly cyanogenic upon tissue disruption. Meanwhile, prunasin levels rapidly declined and were negligible by maturity. During phases II (29-65 DAF) and III (66-81 DAF), the pericarp also accumulated amygdalin, whereas its prunasin content declined toward maturity. Lacking the catabolic enzymes, the pericarp remained acyanogenic throughout all developmental stages. ImagesFigure 2Figure 4 PMID:16668810

Integration of carbohydrate metabolism and redox state controls dauer larva formation in Caenorhabditis elegans.

PubMed

Penkov, Sider; Kaptan, Damla; Erkut, Cihan; Sarov, Mihail; Mende, Fanny; Kurzchalia, Teymuras V

2015-08-20

Under adverse conditions, Caenorhabditis elegans enters a diapause stage called the dauer larva. External cues signal the nuclear hormone receptor DAF-12, the activity of which is regulated by its ligands: dafachronic acids (DAs). DAs are synthesized from cholesterol, with the last synthesis step requiring NADPH, and their absence stimulates dauer formation. Here we show that NADPH levels determine dauer formation in a regulatory mechanism involving key carbohydrate and redox metabolic enzymes. Elevated trehalose biosynthesis diverts glucose-6-phosphate from the pentose phosphate pathway, which is the major source of cellular NADPH. This enhances dauer formation due to the decrease in the DA level. Moreover, DAF-12, in cooperation with DAF-16/FoxO, induces negative feedback of DA synthesis via activation of the trehalose-producing enzymes TPS-1/2 and inhibition of the NADPH-producing enzyme IDH-1. Thus, the dauer developmental decision is controlled by integration of the metabolic flux of carbohydrates and cellular redox potential.

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

PubMed

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.

Nitric Oxide (NO) Measurements in Stomatal Guard Cells.

PubMed

Agurla, Srinivas; Gayatri, Gunja; Raghavendra, Agepati S

2016-01-01

The quantitative measurement of nitric oxide (NO) in plant cells acquired great importance, in view of the multifaceted function and involvement of NO as a signal in various plant processes. Monitoring of NO in guard cells is quite simple because of the large size of guard cells and ease of observing the detached epidermis under microscope. Stomatal guard cells therefore provide an excellent model system to study the components of signal transduction. The levels and functions of NO in relation to stomatal closure can be monitored, with the help of an inverted fluorescence or confocal microscope. We can measure the NO in guard cells by using flouroprobes like 4,5-diamino fluorescein diacetate (DAF-2DA). This fluorescent dye, DAF-2DA, is cell permeable and after entry into the cell, the diacetate group is removed by the cellular esterases. The resulting DAF-2 form is membrane impermeable and reacts with NO to generate the highly fluorescent triazole (DAF-2T), with excitation and emission wavelengths of 488 and 530 nm, respectively. If time-course measurements are needed, the epidermis can be adhered to a cover-glass or glass slide and left in a small petri dishes. Fluorescence can then be monitored at required time intervals; with a precaution that excitation is done minimally, only when a fluorescent image is acquired. The present method description is for the epidermis of Arabidopsis thaliana and Pisum sativum and should work with most of the other dicotyledonous plants.

Electric Vehicles near the Hangar at the Lewis Research Center

NASA Image and Video Library

1977-06-21

The National Aeronautics and Space Administration (NASA) Lewis Research Center tested 16 commercially-manufactured electric vehicles, including these, during the mid-1970s. Lewis and the Energy Research and Development Administration (ERDA) engaged in several energy-related programs in the mid-1970s, including the Electric Vehicle Project. NASA and ERDA undertook the program in 1976 to determine the state of the current electric vehicle technology. The tests were primarily conducted on a 7.5-mile track at the Transportation Research Center located approximately 160 miles southwest of Cleveland, Ohio. Some of the vehicles had analog data recording systems to measure the battery during operation and sensors to determine speed and distance. The tests analyzed the vehicle’s range, acceleration, coast-down, braking, and energy consumption. From left to right: RIPP-Electric, EVA Contactor, Otis P-500, C.H. Waterman DAF, Zagato Elcar, unknown, Sebring-Vanguard Citicar, and Hattronic Minivan

Electroflotation

NASA Astrophysics Data System (ADS)

Chen, Xueming; Chen, Guohua

Electroflotation (EF) is the flotation using electrolytically generated bubbles of hydrogen and oxygen for separating suspended substances from aqueous phases. This process was first proposed by Elmore in 1905 for flotation of valuable minerals from ores. Compared with the conventional dissolved air flotation (DAF), EF has many advantages, including high flotation efficiency, compact units, easy operation, and less maintenance. Therefore, EF is an attractive alternative to DAF. This technique has been proven very effective in treating oily wastewater or oil-water emulsion, mining wastewater, groundwater, food processing wastewater, restaurant wastewater, industrial sewage, heavy metals containing effluent, and many other water and wastewaters.

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

NASA Technical Reports Server (NTRS)

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.

3CE Methodology for Conducting a Modeling, Simulation, and Instrumentation Tool Capability Analysis

DTIC Science & Technology

2010-05-01

flRmurn I F )T:Ir,tir)l! MCr)lto.-lng DHin nttbli..’"Ollc:~ E,;m:a..liut .!,)’l’lt’Mn:l’lll.ll~ t Managemen t F unction a l Arem 1 .5 Toola na...a modeling, simulation, and instrumentation (MS&I) environment. This methodology uses the DoDAF product set to document operational and systems...engineering process were identified and resolved, such as duplication of data elements derived from DoDAF operational and system views used to

Adaptation to delayed auditory feedback induces the temporal recalibration effect in both speech perception and production.

PubMed

Yamamoto, Kosuke; Kawabata, Hideaki

2014-12-01

We ordinarily speak fluently, even though our perceptions of our own voices are disrupted by various environmental acoustic properties. The underlying mechanism of speech is supposed to monitor the temporal relationship between speech production and the perception of auditory feedback, as suggested by a reduction in speech fluency when the speaker is exposed to delayed auditory feedback (DAF). While many studies have reported that DAF influences speech motor processing, its relationship to the temporal tuning effect on multimodal integration, or temporal recalibration, remains unclear. We investigated whether the temporal aspects of both speech perception and production change due to adaptation to the delay between the motor sensation and the auditory feedback. This is a well-used method of inducing temporal recalibration. Participants continually read texts with specific DAF times in order to adapt to the delay. Then, they judged the simultaneity between the motor sensation and the vocal feedback. We measured the rates of speech with which participants read the texts in both the exposure and re-exposure phases. We found that exposure to DAF changed both the rate of speech and the simultaneity judgment, that is, participants' speech gained fluency. Although we also found that a delay of 200 ms appeared to be most effective in decreasing the rates of speech and shifting the distribution on the simultaneity judgment, there was no correlation between these measurements. These findings suggest that both speech motor production and multimodal perception are adaptive to temporal lag but are processed in distinct ways.

Comparative Transcriptome Analysis Reveals Growth-Related Genes in Juvenile Chinese Sea Cucumber, Russian Sea Cucumber, and Their Hybrids.

PubMed

Wang, Zhicheng; Cui, Jun; Song, Jian; Wang, Haoze; Gao, Kailun; Qiu, Xuemei; Gou, Meng; Li, Xin; Hu, Ziwen; Wang, Xiuli; Chang, Yaqing

2018-04-01

Heterosis is important for sea cucumber breeding, but its molecular mechanism remains largely unexplored. In this study, parental lines of Apostichopus japonicus from Russia (R) and China (C) were used to construct hybrids (CR and RC) by reciprocal crossing. We examined the transcriptional profiles of the hybrids (CR and RC) and the purebreds (CC and RR) at different developmental times. A total of 60.27 Gb of clean data was obtained, and 176,649 unigenes were identified, of which 50,312 unigenes were annotated. A total of 414,536 SNPs were identified. A total of 7011 differentially expressed genes (DEGs) were obtained between the purebreds and hybrids at 45 days after fertilization (DAF), and a total of 8218 DEGs were obtained between the purebreds and hybrids at 75 DAF. In addition, a total of 7652 DEGs were obtained between 45 DAF and 75 DAF. The significant DEGs were mainly involved in the MAPK and FOXO signaling pathways, especially in the Ras-Raf-MEK1/2-ERK module, which may be a key regulator of development and growth in juvenile A. japonicus. In addition, we also identified key growth-related genes, such as fgfs, igfs, megfs and hgfs, which were upregulated in the hybrids (RC and CR); these genes may play important roles in heterosis in A. japonicus. Our study provides fundamental information on the molecular mechanisms underlying heterosis in sea cucumber and might suggest strategies for the selection of rapidly growing strains of sea cucumber in aquaculture.

Yellow Pigment Aurovertins Mediate Interactions between the Pathogenic Fungus Pochonia chlamydosporia and Its Nematode Host.

PubMed

Wang, Yan-li; Li, Lin-fang; Li, Dong-xian; Wang, Baile; Zhang, Keqin; Niu, Xuemei

2015-07-29

Nematophagous fungi are globally distributed soil fungi and well-known natural predators of soil-dwelling nematodes. Pochonia chlamydosporia can be found in diverse nematode-suppressive soils as a parasite of nematode eggs and is one of the most studied potential biological control agents of nematodes. However, little is known about the functions of small molecules in the process of infection of nematodes by this parasitic fungus or about small-molecule-mediated interactions between the pathogenic fungus and its host. Our recent study demonstrated that a P. chlamydosporia strain isolated from root knots of tobacco infected by the root-knot nematode Meloidogyne incognita produced a class of yellow pigment metabolite aurovertins, which induced the death of the free-living nematode Panagrellus redivevus. Here we report that nematicidal P. chlamydosporia strains obtained from the nematode worms tended to yield a total yellow pigment aurovertin production exceeding the inhibitory concentration shown in nematicidal bioassays. Aurovertin D was abundant in the pigment metabolites of P. chlamydosporia strains. Aurovertin D showed strong toxicity toward the root-knot nematode M. incognita and exerted profound and detrimental effects on the viability of Caenorhabditis elegans even at a subinhibitory concentration. Evaluation of the nematode mutation in the β subunit of F1-ATPase, together with the application of RNA interference in screening each subunit of F1FO-ATPase in the nematode worms, demonstrated that the β subunit of F1-ATPase might not be the specific target for aurovertins in nematodes. The resistance of C. elegans daf-2(e1370) and the hypersensitivity of C. elegans daf-16(mu86) to aurovertin D indicated that DAF-16/FOXO transcription factor in nematodes was triggered in response to the aurovertin attack. These findings advance our understanding of the roles of aurovertin production in the interactions between nematodes and the pathogen fungus P. chlamydosporia.

The Impact of Body Mass Index on Heterotopic Ossification

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

Mourad, Waleed Fouad, E-mail: Waleed246@gmail.com; Department of Radiation Oncology, Beth Israel Medical Center, New York, NY; Department of Radiation Oncology, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY

2012-04-01

Purpose: To analyze the impact of different body mass index (BMI) as a surrogate marker for heterotopic ossification (HO) in patients who underwent surgical repair (SR) for displaced acetabular fractures (DAF) followed by radiation therapy (RT). Methods and Materials: This is a single-institution retrospective study of 395 patients. All patients underwent SR for DAF followed by RT {+-} indomethacin. All patients received postoperative RT, 7 Gy, within 72 h. The patients were separated into four groups based on their BMI: <18.5, 18.5-24.9, 25-29.9, and >30. The end point of this study was to evaluate the efficacy of RT {+-} indomethacinmore » in preventing HO in patients with different BMI. Results: Analysis of BMI showed an increasing incidence of HO with increasing BMI: <18.5, (0%) 0/6 patients; 18.5-24.9 (6%), 6 of 105 patients developed HO; 25-29.9 (19%), 22 of 117; >30 (31%), 51 of 167. Chi-square and multivariate logistic regression analysis showed that the correlation between odds of HO and BMI is significant, p < 0.0001. As the BMI increased, the risk of HO and Brooker Classes 3, 4 HO increased. The risk of developing HO is 1.0 Multiplication-Sign (10%) more likely among those with higher BMI compared with those with lower BMI. For a one-unit increase in BMI the log odds of HO increases by 1.0, 95% CI (1.06-1.14). Chi-square test shows no significant difference among all other factors and HO (e.g., indomethacin, race, gender). Conclusions: Despite similar surgical treatment and prophylactic measures (RT {+-} indomethacin), the risk of HO appears to significantly increase in patients with higher BMI after DAF. Higher single-fraction doses or multiple fractions and/or combination therapy with nonsteroidal inflammatory drugs may be of greater benefit to these patients.« less

Spatiotemporal regulation of autophagy during Caenorhabditis elegans aging

PubMed Central

Chang, Jessica T; Kumsta, Caroline; Hellman, Andrew B; Adams, Linnea M; Hansen, Malene

2017-01-01

Autophagy has been linked to longevity in many species, but the underlying mechanisms are unclear. Using a GFP-tagged and a new tandem-tagged Atg8/LGG-1 reporter, we quantified autophagic vesicles and performed autophagic flux assays in multiple tissues of wild-type Caenorhabditis elegans and long-lived daf-2/insulin/IGF-1 and glp-1/Notch mutants throughout adulthood. Our data are consistent with an age-related decline in autophagic activity in the intestine, body-wall muscle, pharynx, and neurons of wild-type animals. In contrast, daf-2 and glp-1 mutants displayed unique age- and tissue-specific changes in autophagic activity, indicating that the two longevity paradigms have distinct effects on autophagy during aging. Although autophagy appeared active in the intestine of both long-lived mutants, inhibition of intestinal autophagy significantly abrogated lifespan extension only in glp-1 mutants. Collectively, our data suggest that autophagic activity normally decreases with age in C. elegans, whereas daf-2 and glp-1 long-lived mutants regulate autophagy in distinct spatiotemporal-specific manners to extend lifespan. DOI: http://dx.doi.org/10.7554/eLife.18459.001 PMID:28675140

Use of diaminofluoresceins to detect and measure nitric oxide in low level generating human immune cells.

PubMed

Tiscornia, Adriana; Cairoli, Ernesto; Marquez, Maria; Denicola, Ana; Pritsch, Otto; Cayota, Alfonso

2009-03-15

Nitric oxide ((*)NO) has been implicated in multiple physiological and pathological immune processes. Different methods have been developed to detect and quantify (*)NO, where one of the principal difficulties are the accurately detection in cellular system with low levels of (*)NO production. The choice of the (*)NO detection method to be used depends on the characteristics of the experimental system and the levels of (*)NO production which depend on either the organism source of samples or the experimental conditions. Recently, high sensitive methods to detect and image (*)NO have been reported using 4,5-diaminofluorescein-based fluorescent probes (DAF) and its derivate 4,5-diaminofluorescein diacetate (DAF-2 DA). This work was aimed to adapt and optimize the use of DAF probes to detect and quantify the (*)NO production in systems of high, moderate and low out-put production, especially in human PBMC and their subpopulations. Here, we report an original experimental design which is useful to detect and estimate (*)NO fluxes in human PBMC and their subpopulations with high specificity and sensitivity.

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

PubMed

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.

Role of Caenorhabditis elegans AKT-1/2 and SGK-1 in Manganese Toxicity.

PubMed

Peres, Tanara V; Arantes, Leticia P; Miah, Mahfuzur R; Bornhorst, Julia; Schwerdtle, Tanja; Bowman, Aaron B; Leal, Rodrigo B; Aschner, Michael

2018-06-07

Excessive levels of the essential metal manganese (Mn) may cause a syndrome similar to Parkinson's disease. The model organism Caenorhabditis elegans mimics some of Mn effects in mammals, including dopaminergic neurodegeneration, oxidative stress, and increased levels of AKT. The evolutionarily conserved insulin/insulin-like growth factor-1 signaling pathway (IIS) modulates worm longevity, metabolism, and antioxidant responses by antagonizing the transcription factors DAF-16/FOXO and SKN-1/Nrf-2. AKT-1, AKT-2, and SGK-1 act upstream of these transcription factors. To study the role of these proteins in C. elegans response to Mn intoxication, wild-type N2 and loss-of-function mutants were exposed to Mn (2.5 to 100 mM) for 1 h at the L1 larval stage. Strains with loss-of-function in akt-1, akt-2, and sgk-1 had higher resistance to Mn compared to N2 in the survival test. All strains tested accumulated Mn similarly, as shown by ICP-MS. DAF-16 nuclear translocation was observed by fluorescence microscopy in WT and loss-of-function strains exposed to Mn. qRT-PCR data indicate increased expression of γ-glutamyl cysteine synthetase (GCS-1) antioxidant enzyme in akt-1 mutants. The expression of sod-3 (superoxide dismutase homologue) was increased in the akt-1 mutant worms, independent of Mn treatment. However, dopaminergic neurons degenerated even in the more resistant strains. Dopaminergic function was evaluated with the basal slowing response behavioral test and dopaminergic neuron integrity was evaluated using worms expressing green fluorescent protein (GFP) under the dopamine transporter (DAT-1) promoter. These results suggest that AKT-1/2 and SGK-1 play a role in C. elegans response to Mn intoxication. However, tissue-specific responses may occur in dopaminergic neurons, contributing to degeneration.

FOXO Transcriptional Factors and Long-Term Living

PubMed Central

Rashid, Rehana; Muneer, Saiqa; Hasan, Syed Muhammad Farid

2017-01-01

Several pathologies such as neurodegeneration and cancer are associated with aging, which is affected by many genetic and environmental factors. Healthy aging conceives human longevity, possibly due to carrying the defensive genes. For instance, FOXO (forkhead box O) genes determine human longevity. FOXO transcription factors are involved in the regulation of longevity phenomenon via insulin and insulin-like growth factor signaling. Only one FOXO gene (FOXO DAF-16) exists in invertebrates, while four FOXO genes, that is, FOXO1, FOXO3, FOXO4, and FOXO6 are found in mammals. These four transcription factors are involved in the multiple cellular pathways, which regulate growth, stress resistance, metabolism, cellular differentiation, and apoptosis in mammals. However, the accurate mode of longevity by FOXO factors is unclear until now. This article describes briefly the existing knowledge that is related to the role of FOXO factors in human longevity. PMID:28894507

Effects of oxygen plasma treatment on domestic aramid fiber III reinforced bismaleimide composite interfacial properties

NASA Astrophysics Data System (ADS)

Shi, Chen; Wang, Jing; Chen, Ping; Feng, Jiayue; Cui, Jinyuan; Yang, Faze

2017-12-01

Domestic Aramid Fiber III (DAF III) was modified by oxygen plasma treatment. The fiber surface characteristics was observed by Scanning Electron Microscopy. The results showed that oxygen plasma treatment changed surface morphologies. The effects of oxygen plasma treatment on DAF III reinforced bismaleimides (BMI) composite bending and interfacial properties were investigated, respectively. The ILSS value increased from 49.3 MPa to 56.0 MPa (by 13.5%) after oxygen plasma treatment. The bending strength changed a little. Furthermore, the composite rupture mode changed from interfacial rupture to fiber or resin bulk rupture.

Metabolomic signature associated with reproduction-regulated aging in Caenorhabditis elegans.

PubMed

Wan, Qin-Li; Shi, Xiaohuo; Liu, Jiangxin; Ding, Ai-Jun; Pu, Yuan-Zhu; Li, Zhigang; Wu, Gui-Sheng; Luo, Huai-Rong

2017-02-06

In Caenorhabditis elegans (C. elegans) , ablation of germline stem cells (GSCs) leads to infertility, which extends lifespan. It has been reported that aging and reproduction are both inextricably associated with metabolism. However, few studies have investigated the roles of polar small molecules metabolism in regulating longevity by reproduction. In this work, we combined the nuclear magnetic resonance (NMR) and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) to profile the water-soluble metabolome in C. elegans . Comparing the metabolic fingerprint between two physiological ages among different mutants, our results demonstrate that aging is characterized by metabolome remodeling and metabolic decline. In addition, by analyzing the metabolic profiles of long-lived germline-less glp-1 mutants, we discovered that glp-1 mutants regulate the levels of many age-variant metabolites to attenuate aging, including elevated concentrations of the pyrimidine and purine metabolism intermediates and decreased concentrations of the citric acid cycle intermediates. Interestingly, by analyzing the metabolome of daf-16;glp-1 double mutants, our results revealed that some metabolic exchange contributing to germline-mediated longevity was mediated by transcription factor FOXO/DAF-16, including pyrimidine metabolism and the TCA cycle. Based on a comprehensive metabolic analysis, we provide novel insight into the relationship between longevity and metabolism regulated by germline signals in C. elegans .

Metabolomic signature associated with reproduction-regulated aging in Caenorhabditis elegans

PubMed Central

Wan, Qin-Li; Shi, Xiaohuo; Liu, Jiangxin; Ding, Ai-Jun; Pu, Yuan-Zhu; Li, Zhigang; Wu, Gui-Sheng; Luo, Huai-Rong

2017-01-01

In Caenorhabditis elegans (C. elegans), ablation of germline stem cells (GSCs) leads to infertility, which extends lifespan. It has been reported that aging and reproduction are both inextricably associated with metabolism. However, few studies have investigated the roles of polar small molecules metabolism in regulating longevity by reproduction. In this work, we combined the nuclear magnetic resonance (NMR) and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) to profile the water-soluble metabolome in C. elegans. Comparing the metabolic fingerprint between two physiological ages among different mutants, our results demonstrate that aging is characterized by metabolome remodeling and metabolic decline. In addition, by analyzing the metabolic profiles of long-lived germline-less glp-1 mutants, we discovered that glp-1 mutants regulate the levels of many age-variant metabolites to attenuate aging, including elevated concentrations of the pyrimidine and purine metabolism intermediates and decreased concentrations of the citric acid cycle intermediates. Interestingly, by analyzing the metabolome of daf-16;glp-1 double mutants, our results revealed that some metabolic exchange contributing to germline-mediated longevity was mediated by transcription factor FOXO/DAF-16, including pyrimidine metabolism and the TCA cycle. Based on a comprehensive metabolic analysis, we provide novel insight into the relationship between longevity and metabolism regulated by germline signals in C. elegans PMID:28177875

Innate immunity mediated longevity and longevity induced by germ cell removal converge on the C-type lectin domain protein IRG-7

PubMed Central

Yunger, Elad; Safra, Modi; Levi-Ferber, Mor; Haviv-Chesner, Anat

2017-01-01

In C. elegans, removal of the germline triggers molecular events in the neighboring intestine, which sends an anti-aging signal to the rest of the animal. In this study, we identified an innate immunity related gene, named irg-7, as a novel mediator of longevity in germlineless animals. We consider irg-7 to be an integral downstream component of the germline longevity pathway because its expression increases upon germ cell removal and its depletion interferes with the activation of the longevity-promoting transcription factors DAF-16 and DAF-12 in germlineless animals. Furthermore, irg-7 activation by itself sensitizes the animals' innate immune response and extends the lifespan of animals exposed to live bacteria. This lifespan-extending pathogen resistance relies on the somatic gonad as well as on many genes previously associated with the reproductive longevity pathway. This suggests that these genes are also relevant in animals with an intact gonad, and can affect their resistance to pathogens. Altogether, this study demonstrates the tight association between germline homeostasis and the immune response of animals, and raises the possibility that the reproductive system can act as a signaling center to divert resources towards defending against putative pathogen attacks. PMID:28196094

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.

PubMed

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.

Developmental and Cell Cycle Quiescence Is Mediated by the Nuclear Hormone Receptor Coregulator DIN-1S in the Caenorhabditis elegans Dauer Larva.

PubMed

Colella, Eileen; Li, Shaolin; Roy, Richard

2016-08-01

When faced with suboptimal growth conditions, Caenorhabditis elegans larvae can enter a diapause-like stage called "dauer" that is specialized for dispersal and survival. The decision to form a dauer larva is controlled by three parallel signaling pathways, whereby a compromise of TGFβ, cyclic guanosine monophosphate, or insulin/IGF-like signaling (ILS) results in dauer formation. Signals from these pathways converge on DAF-12, a nuclear hormone receptor that triggers the changes required to initiate dauer formation. DAF-12 is related to the vitamin D, liver-X, and androstane receptors, and like these human receptors, it responds to lipophilic hormone ligands. When bound to its ligand, DAF-12 acquires transcriptional activity that directs reproductive development, while unliganded DAF-12 forms a dauer-specifying complex with its interacting protein DIN-1S to regulate the transcription of genes required for dauer development. We report here that din-1S is required in parallel to par-4/LKB1 signaling within the gonad to establish cell cycle quiescence during the onset of the dauer stage. We show that din-1S is important for postdauer reproduction when ILS is impaired and is necessary for long-term dauer survival in response to reduced ILS. Our work uncovers several previously uncharacterized functions of DIN-1S in executing and maintaining many of the cellular and physiological processes required for appropriate dauer arrest, while also shedding light on the coordination of nuclear hormone signaling, the LKB1/AMPK signaling cascade, and ILS/TGFβ in the control of cell cycle quiescence and tissue growth: a key feature that is often misregulated in a number of hormone-dependent cancers. Copyright © 2016 by the Genetics Society of America.

Effects of floc and bubble size on the efficiency of the dissolved air flotation (DAF) process.

PubMed

Han, Mooyoung; Kim, Tschung-il; Kim, Jinho

2007-01-01

Dissolved air flotation (DAF) is a method for removing particles from water using micro bubbles instead of settlement. The process has proved to be successful and, since the 1960s, accepted as an alternative to the conventional sedimentation process for water and wastewater treatment. However, limited research into the process, especially the fundamental characteristics of bubbles and particles, has been carried out. The single collector collision model is not capable of determining the effects of particular characteristics, such as the size and surface charge of bubbles and particles. Han has published a set of modeling results after calculating the collision efficiency between bubbles and particles by trajectory analysis. His major conclusion was that collision efficiency is maximum when the bubbles and particles are nearly the same size but have opposite charge. However, experimental verification of this conclusion has not been carried out yet. This paper describes a new method for measuring the size of particles and bubbles developed using computational image analysis. DAF efficiency is influenced by the effect of the recycle ratio on various average floc sizes. The larger the recycle ratio, the higher the DAF efficiency at the same pressure and particle size. The treatment efficiency is also affected by the saturation pressure, because the bubble size and bubble volume concentration are controlled by the pressure. The highest efficiency is obtained when the floc size is larger than the bubble size. These results, namely that the highest collision efficiency occurs when the particles and bubbles are about the same size, are more in accordance with the trajectory model than with the white water collector model, which implies that the larger the particles, the higher is the collision efficiency.

Specific regulation of thermosensitive lipid droplet fusion by a nuclear hormone receptor pathway

PubMed Central

Li, Shiwei; Li, Qi; Kong, Yuanyuan; Wu, Shuang; Cui, Qingpo; Zhang, Mingming; Zhang, Shaobing O.

2017-01-01

Nuclear receptors play important roles in regulating fat metabolism and energy production in humans. The regulatory functions and endogenous ligands of many nuclear receptors are still unidentified, however. Here, we report that CYP-37A1 (ortholog of human cytochrome P450 CYP4V2), EMB-8 (ortholog of human P450 oxidoreductase POR), and DAF-12 (homolog of human nuclear receptors VDR/LXR) constitute a hormone synthesis and nuclear receptor pathway in Caenorhabditis elegans. This pathway specifically regulates the thermosensitive fusion of fat-storing lipid droplets. CYP-37A1, together with EMB-8, synthesizes a lipophilic hormone not identical to Δ7-dafachronic acid, which represses the fusion-promoting function of DAF-12. CYP-37A1 also negatively regulates thermotolerance and lifespan at high temperature in a DAF-12–dependent manner. Human CYP4V2 can substitute for CYP-37A1 in C. elegans. This finding suggests the existence of a conserved CYP4V2-POR–nuclear receptor pathway that functions in converting multilocular lipid droplets to unilocular ones in human cells; misregulation of this pathway may lead to pathogenic fat storage. PMID:28760992

Specific regulation of thermosensitive lipid droplet fusion by a nuclear hormone receptor pathway.

PubMed

Li, Shiwei; Li, Qi; Kong, Yuanyuan; Wu, Shuang; Cui, Qingpo; Zhang, Mingming; Zhang, Shaobing O

2017-08-15

Nuclear receptors play important roles in regulating fat metabolism and energy production in humans. The regulatory functions and endogenous ligands of many nuclear receptors are still unidentified, however. Here, we report that CYP-37A1 (ortholog of human cytochrome P450 CYP4V2), EMB-8 (ortholog of human P450 oxidoreductase POR), and DAF-12 (homolog of human nuclear receptors VDR/LXR) constitute a hormone synthesis and nuclear receptor pathway in Caenorhabditis elegans This pathway specifically regulates the thermosensitive fusion of fat-storing lipid droplets. CYP-37A1, together with EMB-8, synthesizes a lipophilic hormone not identical to Δ7-dafachronic acid, which represses the fusion-promoting function of DAF-12. CYP-37A1 also negatively regulates thermotolerance and lifespan at high temperature in a DAF-12-dependent manner. Human CYP4V2 can substitute for CYP-37A1 in C. elegans This finding suggests the existence of a conserved CYP4V2-POR-nuclear receptor pathway that functions in converting multilocular lipid droplets to unilocular ones in human cells; misregulation of this pathway may lead to pathogenic fat storage.

FDA-approved drugs that protect mammalian neurons from glucose toxicity slow aging dependent on cbp and protect against proteotoxicity.

PubMed

Lublin, Alex; Isoda, Fumiko; Patel, Harshil; Yen, Kelvin; Nguyen, Linda; Hajje, Daher; Schwartz, Marc; Mobbs, Charles

2011-01-01

Screening a library of drugs with known safety profiles in humans yielded 30 drugs that reliably protected mammalian neurons against glucose toxicity. Subsequent screening demonstrated that 6 of these 30 drugs increase lifespan in C. elegans: caffeine, ciclopirox olamine, tannic acid, acetaminophen, bacitracin, and baicalein. Every drug significantly reduced the age-dependent acceleration of mortality rate. These protective effects were blocked by RNAi inhibition of cbp-1 in adults only, which also blocks protective effects of dietary restriction. Only 2 drugs, caffeine and tannic acid, exhibited a similar dependency on DAF-16. Caffeine, tannic acid, and bacitracin also reduced pathology in a transgenic model of proteotoxicity associated with Alzheimer's disease. These results further support a key role for glucose toxicity in driving age-related pathologies and for CBP-1 in protection against age-related pathologies. These results also provide novel lead compounds with known safety profiles in human for treatment of age-related diseases, including Alzheimer's disease and diabetic complications.

Larval crowding accelerates C. elegans development and reduces lifespan.

PubMed

Ludewig, Andreas H; Gimond, Clotilde; Judkins, Joshua C; Thornton, Staci; Pulido, Dania C; Micikas, Robert J; Döring, Frank; Antebi, Adam; Braendle, Christian; Schroeder, Frank C

2017-04-01

Environmental conditions experienced during animal development are thought to have sustained impact on maturation and adult lifespan. Here we show that in the model organism C. elegans developmental rate and adult lifespan depend on larval population density, and that this effect is mediated by excreted small molecules. By using the time point of first egg laying as a marker for full maturity, we found that wildtype hermaphrodites raised under high density conditions developed significantly faster than animals raised in isolation. Population density-dependent acceleration of development (Pdda) was dramatically enhanced in fatty acid β-oxidation mutants that are defective in the biosynthesis of ascarosides, small-molecule signals that induce developmental diapause. In contrast, Pdda is abolished by synthetic ascarosides and steroidal ligands of the nuclear hormone receptor DAF-12. We show that neither ascarosides nor any known steroid hormones are required for Pdda and that another chemical signal mediates this phenotype, in part via the nuclear hormone receptor NHR-8. Our results demonstrate that C. elegans development is regulated by a push-pull mechanism, based on two antagonistic chemical signals: chemosensation of ascarosides slows down development, whereas population-density dependent accumulation of a different chemical signal accelerates development. We further show that the effects of high larval population density persist through adulthood, as C. elegans larvae raised at high densities exhibit significantly reduced adult lifespan and respond differently to exogenous chemical signals compared to larvae raised at low densities, independent of density during adulthood. Our results demonstrate how inter-organismal signaling during development regulates reproductive maturation and longevity.

Larval crowding accelerates C. elegans development and reduces lifespan

PubMed Central

Ludewig, Andreas H.; Gimond, Clotilde; Judkins, Joshua C.; Thornton, Staci; Pulido, Dania C.; Micikas, Robert J.; Döring, Frank; Antebi, Adam; Braendle, Christian; Schroeder, Frank C.

2017-01-01

Environmental conditions experienced during animal development are thought to have sustained impact on maturation and adult lifespan. Here we show that in the model organism C. elegans developmental rate and adult lifespan depend on larval population density, and that this effect is mediated by excreted small molecules. By using the time point of first egg laying as a marker for full maturity, we found that wildtype hermaphrodites raised under high density conditions developed significantly faster than animals raised in isolation. Population density-dependent acceleration of development (Pdda) was dramatically enhanced in fatty acid β-oxidation mutants that are defective in the biosynthesis of ascarosides, small-molecule signals that induce developmental diapause. In contrast, Pdda is abolished by synthetic ascarosides and steroidal ligands of the nuclear hormone receptor DAF-12. We show that neither ascarosides nor any known steroid hormones are required for Pdda and that another chemical signal mediates this phenotype, in part via the nuclear hormone receptor NHR-8. Our results demonstrate that C. elegans development is regulated by a push-pull mechanism, based on two antagonistic chemical signals: chemosensation of ascarosides slows down development, whereas population-density dependent accumulation of a different chemical signal accelerates development. We further show that the effects of high larval population density persist through adulthood, as C. elegans larvae raised at high densities exhibit significantly reduced adult lifespan and respond differently to exogenous chemical signals compared to larvae raised at low densities, independent of density during adulthood. Our results demonstrate how inter-organismal signaling during development regulates reproductive maturation and longevity. PMID:28394895

Evaluate Rijsimulator-Instellingen Voor de DAF YA-4440 (Evaluation Drive Simulator Settings for DAF YA-4440)

DTIC Science & Technology

1991-10-01

waarbij: 0c1 staat voor de beginsnclhcid; cl = 24 K1 C= (3/25) K2 C= 5 K4 Merk op dat 0o cxponenticcl afhankelijk is van t. TNO-rapport Pagina 9 Voor (KI...gegeven: cgt) = sqrt(ci/C3)*tan(arctan(sqr((c 3/c1 )*w0 )) - sqrl(c1 *C3)*t/C4) ( 9 ) waarbij: cl= -24 K, C= 3 1(3/500 C4= 5 K4~ Merk op dat (o niet-lincair...wcrgegevcn. Omdat K, kiciner is dan K4 heeft con kicine absolute verandering in K, grotere gevolgen voor de UDB-uitrolcurve dan en kieinc verandoring in

A mir-231-Regulated Protection Mechanism against the Toxicity of Graphene Oxide in Nematode Caenorhabditis elegans

PubMed Central

Yang, Ruilong; Ren, Mingxia; Rui, Qi; Wang, Dayong

2016-01-01

Recently, several dysregulated microRNAs (miRNAs) have been identified in organisms exposed to graphene oxide (GO). However, their biological functions and mechanisms of the action are still largely unknown. Here, we investigated the molecular mechanism of mir-231 in the regulation of GO toxicity using in vivo assay system of Caenorhabditis elegans. We found that GO exposure inhibited the expression of mir-231::GFP in multiple tissues, in particular in the intestine. mir-231 acted in intestine to regulate the GO toxicity, and overexpression of mir-231 in intestine caused a susceptible property of nematodes to GO toxicity. smk-1 encoding a homologue to mammalian SMEK functioned as a targeted gene for mir-231, and was also involved in the intestinal regulation of GO toxicity. Mutation of smk-1 gene induced a susceptible property to GO toxicity, whereas the intestinal overexpression of smk-1 resulted in a resistant property to GO toxicity. Moreover, mutation of smk-1 gene suppressed the resistant property of mir-231 mutant to GO toxicity. In nematodes, SMK-1 further acted upstream of the transcriptional factor DAF-16/FOXO in insulin signaling pathway to regulate GO toxicity. Therefore, mir-231 may encode a GO-responsive protection mechanism against the GO toxicity by suppressing the function of the SMK-1 - DAF-16 signaling cascade in nematodes. PMID:27558892

A mir-231-Regulated Protection Mechanism against the Toxicity of Graphene Oxide in Nematode Caenorhabditis elegans

NASA Astrophysics Data System (ADS)

Yang, Ruilong; Ren, Mingxia; Rui, Qi; Wang, Dayong

2016-08-01

Recently, several dysregulated microRNAs (miRNAs) have been identified in organisms exposed to graphene oxide (GO). However, their biological functions and mechanisms of the action are still largely unknown. Here, we investigated the molecular mechanism of mir-231 in the regulation of GO toxicity using in vivo assay system of Caenorhabditis elegans. We found that GO exposure inhibited the expression of mir-231::GFP in multiple tissues, in particular in the intestine. mir-231 acted in intestine to regulate the GO toxicity, and overexpression of mir-231 in intestine caused a susceptible property of nematodes to GO toxicity. smk-1 encoding a homologue to mammalian SMEK functioned as a targeted gene for mir-231, and was also involved in the intestinal regulation of GO toxicity. Mutation of smk-1 gene induced a susceptible property to GO toxicity, whereas the intestinal overexpression of smk-1 resulted in a resistant property to GO toxicity. Moreover, mutation of smk-1 gene suppressed the resistant property of mir-231 mutant to GO toxicity. In nematodes, SMK-1 further acted upstream of the transcriptional factor DAF-16/FOXO in insulin signaling pathway to regulate GO toxicity. Therefore, mir-231 may encode a GO-responsive protection mechanism against the GO toxicity by suppressing the function of the SMK-1 - DAF-16 signaling cascade in nematodes.

Knock-out of a mitochondrial sirtuin protects neurons from degeneration in Caenorhabditis elegans.

PubMed

Sangaletti, Rachele; D'Amico, Massimo; Grant, Jeff; Della-Morte, David; Bianchi, Laura

2017-08-01

Sirtuins are NAD⁺-dependent deacetylases, lipoamidases, and ADP-ribosyltransferases that link cellular metabolism to multiple intracellular pathways that influence processes as diverse as cell survival, longevity, and cancer growth. Sirtuins influence the extent of neuronal death in stroke. However, different sirtuins appear to have opposite roles in neuronal protection. In Caenorhabditis elegans, we found that knock-out of mitochondrial sirtuin sir-2.3, homologous to mammalian SIRT4, is protective in both chemical ischemia and hyperactive channel induced necrosis. Furthermore, the protective effect of sir-2.3 knock-out is enhanced by block of glycolysis and eliminated by a null mutation in daf-16/FOXO transcription factor, supporting the involvement of the insulin/IGF pathway. However, data in Caenorhabditis elegans cell culture suggest that the effects of sir-2.3 knock-out act downstream of the DAF-2/IGF-1 receptor. Analysis of ROS in sir-2.3 knock-out reveals that ROS become elevated in this mutant under ischemic conditions in dietary deprivation (DD), but to a lesser extent than in wild type, suggesting more robust activation of a ROS scavenging system in this mutant in the absence of food. This work suggests a deleterious role of SIRT4 during ischemic processes in mammals that must be further investigated and reveals a novel pathway that can be targeted for the design of therapies aimed at protecting neurons from death in ischemic conditions.

Coagulation, flocculation, dissolved air flotation and filtration in the removal of Giardia spp. and Cryptosporidium spp. from water supply.

PubMed

Andreoli, Fernando César; Sabogal-Paz, Lyda Patricia

2017-11-15

Removing protozoa from a water supply using coagulation, flocculation, dissolved air flotation (DAF) and filtration on a bench scale was evaluated. Calcium carbonate flocculation with and without immunomagnetic separation (IMS) was chosen to detect Giardia spp. cysts and Cryptosporidium spp. oocysts in the studied samples. The results indicated that DAF removed between 1.31 log and 1.79 log of cysts and between 1.08 log and 1.42 log of oocysts. The performance was lower in filtration, with the removal of 1.07 log-1.44 log for cysts and 0.82 log-0.98 log for oocysts. The coagulation, flocculation, DAF and filtration steps removed more than 2.2 log of cysts and oocysts from the water studied. However, protozoa were detected in the filtered water, even with turbidity values of 0.2 NTU. The recovery of the detection method met the international criteria and was higher when there was no IMS. Including the third acid dissociation in the IMS was critical to improve the performance of the protocol tested. However, there was an increase in the technical and analytical complexity and costs. It was also observed that the efficiency of the treatment was linked to the performance of the selected method of detecting protozoa.

Highlighting the importance of transitional ventilation regimes in the management of Mediterranean show caves (Nerja-Pintada system, southern Spain).

PubMed

Liñán, C; Del Rosal, Y; Carrasco, F; Vadillo, I; Benavente, J; Ojeda, L

2018-08-01

This study shows the utilization of the air CO 2 exhaled by a very high number of visitors in the Nerja Cave as both a tracer and an additional tool to precisely evaluate the air circulation through the entire karst system, which includes non-touristic passages, originally free of anthropogenic CO 2 . The analysis of the temporal - spatial evolution of the CO 2 content and other monitoring data measured from January 2015 to December 2016 in the Nerja-Pintada system, including air microbiological controls, has allowed us to define a new general ventilation model, of great interest for the conservation of the subterranean environment. During the annual cycle four different ventilation regimes and two ventilation modes (UAF-mode and DAF-mode) exist which determine the significance of the anthropogenic impact within the caves. During the winter regime, the strong ventilation regime and the airflow directions from the lowest to the highest entrance (UAF-mode) contribute to the rapid elimination of anthropogenic CO 2 , and this affects the whole karstic system. During the summer regime the DAF-mode ventilation (with airflows from the highest to the lowest entrances) is activated. Although the number of visitors is maximum and the natural ventilation of the karstic system is the lowest of the annual cycle, the anthropogenic impact only affects the Tourist Galleries. The transitional ventilation regimes -spring and autumn- are the most complex of the annual cycle, with changing air-flow directions (from UAF-mode to DAF-mode and vice versa) at diurnal and poly diurnal scale, which conditions the range of the anthropogenic impact in each sector of the karst system. The activation of the DAF-mode has been observed when the temperature difference between the external and air cave is higher than 5°C. Copyright © 2018 Elsevier B.V. All rights reserved.

Combining sun-based technologies (microalgae and solar disinfection) for urban wastewater regeneration.

PubMed

Gutiérrez-Alfaro, Sergio; Rueda-Márquez, Juan J; Perales, José A; Manzano, Manuel A

2018-04-01

Solar disinfection (SODIS) of urban wastewater can be a suitable technology for improving the microbiological quality of reclaimed water as a complement to other extensive and environmentally friendly technologies such as microalgae biotreatment. The objective of this work is to evaluate the feasibility of incorporating the SODIS technology at the end of a pilot scale urban wastewater treatment plant (WWTP) where the processes are based on microalgae biotechnology and comprising three Upflow Anaerobic Sludge Blanket (UASB, 20m 3 each one) reactor, six High Rate Algal Ponds (HRAP, 32m 2 each one), and a Dissolved Air Flotation (DAF, 1m 3 ) unit. E. coli concentration was monitored at the effluent of the different units (UASB, HRAP, DAF) of the pilot WWTP. The efficiency of the SODIS process was studied for the inactivation of three of the commonly employed indicator microorganisms (Escherichia coli, Enterococcus spp. and Clostridium perfringens) using a compound parabolic collector (CPC) for five months under various conditions of irradiance and temperature. E. coli and Enterococcus spp. were more effectively disinfected by the SODIS unit (2.9 and 2.5 logarithms of reduction on average, respectively) than by the HRAP (2 and 1.1) or the DAF (0.9 and 0.1). On the contrary, the DAF technology achieved better reduction rates of C. perfringens (1.7) than the SODIS (0.9) and the HRAP (0.1). No regrowth of any microorganisms was detected during dark storage after the SODIS treatment. Incorporating a SODIS unit after the non-conventional WWTP processes substantially increases the possibilities for reuse of the treated water after receiving a cumulative UV radiation dose of 25W·h/m 2 (50min of normalized time of solar illumination). The surface requirement of the SODIS equipment would be 3.5 times smaller than the HRAP's surface. Copyright © 2017 Elsevier B.V. All rights reserved.

Stuttering adults' lack of pre-speech auditory modulation normalizes when speaking with delayed auditory feedback.

PubMed

Daliri, Ayoub; Max, Ludo

2018-02-01

Auditory modulation during speech movement planning is limited in adults who stutter (AWS), but the functional relevance of the phenomenon itself remains unknown. We investigated for AWS and adults who do not stutter (AWNS) (a) a potential relationship between pre-speech auditory modulation and auditory feedback contributions to speech motor learning and (b) the effect on pre-speech auditory modulation of real-time versus delayed auditory feedback. Experiment I used a sensorimotor adaptation paradigm to estimate auditory-motor speech learning. Using acoustic speech recordings, we quantified subjects' formant frequency adjustments across trials when continually exposed to formant-shifted auditory feedback. In Experiment II, we used electroencephalography to determine the same subjects' extent of pre-speech auditory modulation (reductions in auditory evoked potential N1 amplitude) when probe tones were delivered prior to speaking versus not speaking. To manipulate subjects' ability to monitor real-time feedback, we included speaking conditions with non-altered auditory feedback (NAF) and delayed auditory feedback (DAF). Experiment I showed that auditory-motor learning was limited for AWS versus AWNS, and the extent of learning was negatively correlated with stuttering frequency. Experiment II yielded several key findings: (a) our prior finding of limited pre-speech auditory modulation in AWS was replicated; (b) DAF caused a decrease in auditory modulation for most AWNS but an increase for most AWS; and (c) for AWS, the amount of auditory modulation when speaking with DAF was positively correlated with stuttering frequency. Lastly, AWNS showed no correlation between pre-speech auditory modulation (Experiment II) and extent of auditory-motor learning (Experiment I) whereas AWS showed a negative correlation between these measures. Thus, findings suggest that AWS show deficits in both pre-speech auditory modulation and auditory-motor learning; however, limited pre-speech modulation is not directly related to limited auditory-motor adaptation; and in AWS, DAF paradoxically tends to normalize their otherwise limited pre-speech auditory modulation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Carlina acaulis Exhibits Antioxidant Activity and Counteracts Aβ Toxicity in Caenorhabditis elegans.

PubMed

Link, Pille; Roth, Kevin; Sporer, Frank; Wink, Michael

2016-07-02

Carlina acaulis is a medicinal plant that has shown antioxidant activity in in vitro studies, but to date no corresponding in vivo data is available. Therefore, in the present study the antioxidant activity and its impact in counteracting Aβ toxicity were studied in the Caenorhabditis elegans model. A dichloromethane extract of the roots of C. acaulis was prepared and characterised via gas-liquid-chromatography/mass-spectrometry (GLC-MS). The in vitro antioxidant activity was confirmed via 2,2-diphenyl-1-picrylhydracyl assay. The extract was further separated by thin layer chromatography into two fractions, one of which was a fraction of the dichloromethane extract of C. acaulis containing mostly Carlina oxide (CarOx). Different strains of C. elegans were employed to study the expression of hsp-16.2p::GFP as a marker for oxidative stress, delocalisation of the transcription factor DAF-16 as a possible mechanism of antioxidant activity, the effect of the drug under lethal oxidative stress, and the effect against beta-amyloid (Aβ) toxicity in a paralysis assay. The C. acaulis extract and CarOx showed high antioxidant activity (stress reduction by 47% and 64%, respectively) in C. elegans and could activate the transcription factor DAF-16 which directs the expression of anti-stress genes. In paralysis assay, only the total extract was significantly active, delaying paralysis by 1.6 h. In conclusion, in vivo antioxidant activity was shown for C. acaulis for the first time in the C. elegans model. The active antioxidant compound is Carlina oxide. This activity, however, is not sufficient to counteract Aβ toxicity. Other mechanisms and possibly other active compounds are involved in this effect.

Energy status of ripening and postharvest senescent fruit of litchi (Litchi chinensis Sonn.)

PubMed Central

2013-01-01

Background Recent studies have demonstrated that cellular energy is a key factor switching on ripening and senescence of fruit. However, the factors that influence fruit energy status remain largely unknown. Results HPLC profiling showed that ATP abundance increased significantly in developing preharvest litchi fruit and was strongly correlated with fruit fresh weight. In contrast, ATP levels declined significantly during postharvest fruit senescence and were correlated with the decrease in the proportion of edible fruit. The five gene transcripts isolated from the litchi fruit pericarp were highly expressed in vegetative tissues and peaked at 70 days after flowering (DAF) consistent with fruit ADP concentrations, except for uncoupling mitochondrial protein 1 (UCP1), which was predominantly expressed in the root, and ATP synthase beta subunit (AtpB), which was up-regulated significantly before harvest and peaked 2 days after storage. These results indicated that the color-breaker stage at 70 DAF and 2 days after storage may be key turning points in fruit energy metabolism. Transcript abundance of alternative oxidase 1 (AOX1) increased after 2 days of storage to significantly higher levels than those of LcAtpB, and was down-regulated significantly by exogenous ATP. ATP supplementation had no significant effect on transcript abundance of ADP/ATP carrier 1 (AAC1) and slowed the changes in sucrose non-fermenting-1-related kinase 2 (SnRK2) expression, but maintained ATP and energy charge levels, which were correlated with delayed senescence. Conclusions Our results suggest that senescence of litchi fruit is closely related with energy. A surge of LcAtpB expression marked the beginning of fruit senescence. The findings may provide a new strategy to extend fruit shelf life by regulating its energy level. PMID:23547657

The temporal scaling of Caenorhabditis elegans ageing.

PubMed

Stroustrup, Nicholas; Anthony, Winston E; Nash, Zachary M; Gowda, Vivek; Gomez, Adam; López-Moyado, Isaac F; Apfeld, Javier; Fontana, Walter

2016-02-04

The process of ageing makes death increasingly likely, involving a random aspect that produces a wide distribution of lifespan even in homogeneous populations. The study of this stochastic behaviour may link molecular mechanisms to the ageing process that determines lifespan. Here, by collecting high-precision mortality statistics from large populations, we observe that interventions as diverse as changes in diet, temperature, exposure to oxidative stress, and disruption of genes including the heat shock factor hsf-1, the hypoxia-inducible factor hif-1, and the insulin/IGF-1 pathway components daf-2, age-1, and daf-16 all alter lifespan distributions by an apparent stretching or shrinking of time. To produce such temporal scaling, each intervention must alter to the same extent throughout adult life all physiological determinants of the risk of death. Organismic ageing in Caenorhabditis elegans therefore appears to involve aspects of physiology that respond in concert to a diverse set of interventions. In this way, temporal scaling identifies a novel state variable, r(t), that governs the risk of death and whose average decay dynamics involves a single effective rate constant of ageing, kr. Interventions that produce temporal scaling influence lifespan exclusively by altering kr. Such interventions, when applied transiently even in early adulthood, temporarily alter kr with an attendant transient increase or decrease in the rate of change in r and a permanent effect on remaining lifespan. The existence of an organismal ageing dynamics that is invariant across genetic and environmental contexts provides the basis for a new, quantitative framework for evaluating the manner and extent to which specific molecular processes contribute to the aspect of ageing that determines lifespan.

The temporal scaling of Caenorhabditis elegans ageing

NASA Astrophysics Data System (ADS)

Stroustrup, Nicholas; Anthony, Winston E.; Nash, Zachary M.; Gowda, Vivek; Gomez, Adam; López-Moyado, Isaac F.; Apfeld, Javier; Fontana, Walter

2016-02-01

The process of ageing makes death increasingly likely, involving a random aspect that produces a wide distribution of lifespan even in homogeneous populations. The study of this stochastic behaviour may link molecular mechanisms to the ageing process that determines lifespan. Here, by collecting high-precision mortality statistics from large populations, we observe that interventions as diverse as changes in diet, temperature, exposure to oxidative stress, and disruption of genes including the heat shock factor hsf-1, the hypoxia-inducible factor hif-1, and the insulin/IGF-1 pathway components daf-2, age-1, and daf-16 all alter lifespan distributions by an apparent stretching or shrinking of time. To produce such temporal scaling, each intervention must alter to the same extent throughout adult life all physiological determinants of the risk of death. Organismic ageing in Caenorhabditis elegans therefore appears to involve aspects of physiology that respond in concert to a diverse set of interventions. In this way, temporal scaling identifies a novel state variable, r(t), that governs the risk of death and whose average decay dynamics involves a single effective rate constant of ageing, kr. Interventions that produce temporal scaling influence lifespan exclusively by altering kr. Such interventions, when applied transiently even in early adulthood, temporarily alter kr with an attendant transient increase or decrease in the rate of change in r and a permanent effect on remaining lifespan. The existence of an organismal ageing dynamics that is invariant across genetic and environmental contexts provides the basis for a new, quantitative framework for evaluating the manner and extent to which specific molecular processes contribute to the aspect of ageing that determines lifespan.

The temporal scaling of Caenorhabditis elegans ageing

PubMed Central

Stroustrup, Nicholas; Anthony, Winston E.; Nash, Zachary M.; Gowda, Vivek; Gomez, Adam; López-Moyado, Isaac F.; Apfeld, Javier; Fontana, Walter

2016-01-01

The process of ageing makes death increasingly likely, but involves a random aspect that produces a wide distribution of lifespan even in homogeneous populations1,2. The study of this stochastic behaviour may link molecular mechanisms to the ageing process that determines lifespan. Here, by collecting high-precision mortality statistics from large populations, we observe that interventions as diverse as changes in diet, temperature, exposure to oxidative stress, and disruption of genes including the heat shock factor hsf-1, the hypoxia-inducible factor hif-1, and the insulin/IGF-1 pathway components daf-2, age-1, and daf-16 all alter lifespan distributions by an apparent stretching or shrinking of time. To produce such temporal scaling, each intervention must alter to the same extent throughout adult life all physiological determinants of the risk of death. Organismic ageing in Caenorhabditis elegans therefore appears to involve aspects of physiology that respond in concert to a diverse set of interventions. In this way, temporal scaling identifies a novel state variable, r(t), that governs the risk of death and whose average decay dynamics involves a single effective rate constant of ageing, kr. Interventions that produce temporal scaling influence lifespan exclusively by altering kr. Such interventions, when applied transiently even in early adulthood, temporarily alter kr with an attendant transient increase or decrease in the rate of change in r and a permanent effect on remaining lifespan. The existence of an organismal ageing dynamics that is invariant across genetic and environmental contexts provides the basis for a new, quantitative framework for evaluating how and how much specific molecular processes contribute to the aspect of ageing that determines lifespan. PMID:26814965

Identification and transcript profiles of citrus growth-regulating factor genes involved in the regulation of leaf and fruit development.

PubMed

Liu, Xiao; Guo, Ling-Xia; Jin, Long-Fei; Liu, Yong-Zhong; Liu, Tao; Fan, Yu-Hua; Peng, Shu-Ang

2016-10-01

Growth-regulating factor (GRF) is an important protein in GA-mediated response, with key roles in plant growth and development. However, it is not known whether or how the GRF proteins in citrus to regulate organ size. In this study, nine citrus GRF genes (CsGRF1-9) were validated from the 'Anliu' sweet orange (AL, Citrus sinensis cv. Anliu) by PCR amplification. They all contain two conserved motifs (QLQ and WRC) and have 3-4 exons. The transcript levels of genes were detected by qRT-PCR. Transcript analysis showed that (1) CsGRF 1, 2, 5, 6, 7, and 9 expressed predominantly in young leaf, CsGRF 3 and 4 expressed predominantly in fruit immature juice sacs and CsGRF 8 expressed predominantly in root; (2) all citrus GRF genes had significantly higher expression in young leaves than mature leaf; (3) in juice sacs, the transcript levels of CsGRF1, 4, 5, 6, and 8 increased significantly while the transcript levels of CsGRF2, 3, 7, and 9 had no significant change from 80 DAF to 100 DAF. Besides, GA3 treatment did not affect the transcript levels of CsGRF5 and CsGRF6 but significantly increased the transcript levels of the other seven CsGRF genes in young leaves. These results suggested that all CsGRF genes involve in the leaf development, CsGRF1, 4, 5, 6, and 8 act developmentally whilst CsGRF2, 3, 7, and 9 play fundamental roles in fruit cell enlargement, which may be through GA pathway or GA-independent pathway.

Development of dissolved air flotation technology from the first generation to the newest (third) one (DAF in turbulent flow conditions).

PubMed

Kiuru, H J

2001-01-01

This paper gives a brief description of the development of dissolved air flotation DAF (or so-called high pressure flotation) as an unit operation for removal of solids in water and wastewater treatment during the last 80 years up to this time. The first DAF-systems used in the water industry were the ADKA and Sveen-Pedersen ones from the 1920s. Some of these are still in use. The tanks in which the flotation phenomenon takes place in these systems are very shallow and narrow as well as rather long. The flow rate of water is some 2-3 m/h (at most less than 5 m/h only) and there is a very thin micro-bubble blanket below the water surface between the dry sludge blanket on that and the clarified water which flows almost horizontally below the bubble blanket toward the end of the tanks to be taken out there from near the bottom. The second generation of DAF was introduced in the 1960s and these units are widely in use today. Their tanks are almost square ones having usually a little bit more length than breadth. They are rather deep, too. There is an under-flow wall in front of the back wall of the units having a narrow horizontal gap on the bottom of the tanks for letting out the clarified water from the flotation space. The flow rate of water is usually 5-7 m/h or at most less than 10 m/h. The direction of flow is 30-45 degrees below the horizontal. There is a rather thick micro-bubble bed at the beginning of the tank below the dry sludge blanket. This bubble-bed becomes clearly thinner, when going toward the end of the tank. There are also round DAF tanks which are based on the same hydraulic principles as the rectangular ones presented above. A special application of DAF called the flotation filter was invented at the very end of the 1960s. It is a combination of flotation and rapid sand filtration, both of those being placed in the same tank. Flotation takes place in the upper part of the tank and the filter has been placed in the lower part of it. The direction of water flow is now vertically down from the free surface of water in the tank toward the deep-bed filter. This controls the direction of flow in the flotation space of the tank above the filter bed. The flow rate of water in flotation filters may be 10-15 m/h, but the flow conditions are still laminar. It is the threat that the head-loss of filters would grow too rapidly which in practice is limiting the hydraulic flow rate of flotation filters in this area. The third generation of DAF has been developed at the end of the 1990s. The operational idea is based on that of the flotation filter. The filter bed on the bottom of the tank has been replaced by a thin stiff plate with plenty of round orifices throughout the plate. This plate, having a very much lower flowing resistance than a sand filter can have, controls the vertical flow of water in the flotation space above the plate and distributes it evenly throughout the horizontal cross-section of the tank. The flotation tank is almost square seen from above and its depth is clearly more than the length and breadth of it. This kind of flotation unit can be operated with flow rates of water in the range 25-40 m/l. Even a flow rate of more than 60 m/h has been reported from this kind of DAF-units. There is no risk of clogging of the plate by suspended solids which could limit the flow rate. This is to say that it is possible to operate DAF also in turbulent flow conditions. The depth of the micro-bubble bed below the surface of water can be 1.5-2.5 m. There actually is a continuously regenerated micro-bubble bed in the tank filtering water which is going through this bed. The lower surface of the micro-bubble bed is really a horizontal one a little bit above the plate controlling the flow in the flotation space. The clarified water below the micro-bubble bed is totally clear. It can be said that in this case the removal of suspended solids takes place much more by filtering water by a deep-bed micro-bubble filter than by attaching micro-bubbles onto solids, when both of these are mixed with each other in the inlet shaft of the flotation unit, because the retention time of water in the inlet shaft is very short indeed.

Synthesis of minoxidil conjugates and their evaluation as HL-60 differentiation agents.

PubMed

Stoica, Sonia; Magoulas, George E; Antoniou, Antonia I; Suleiman, Sherif; Cassar, Analisse; Gatt, Lucienne; Papaioannou, Dionissios; Athanassopoulos, Constantinos M; Schembri-Wismayer, Pierre

2016-02-15

Activation of minoxidil (MNX) with N,N'-carbonyldiimidazole and coupling with natural polyamines (PAs) and commercially available aliphatic or aromatic amines provided a series of new conjugates which were evaluated for their ability to induce differentiation to HL-60 acute myeloid leukemia cancer cells, using a modified NBTZ reduction test. Although neither MNX nor 4,4'-methylenedianiline (MDA) or 2,7-diaminofluorene (DAF), alone or in combination, had any effect, the MNX-spermine (SPM) conjugate (11) and the conjugates 7 and 8 of MNX with MDA and DAF exhibited a differentiation-inducing effect at a concentration of 10 μM without being toxic on proliferating human peripheral blood mononuclear cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

Deployable Air Beam Fender System (DAFS): Energy Absorption Performance Analysis

DTIC Science & Technology

2007-03-30

impacts. The main energy-absorbing component of DAFS is the flexible cylindrical pressure vessel (figure 3), which is constructed of a woven, coated fabric...96Co60rfss ar Fiur 16.atca Normali"ed Volme Versusm Percen04-t DiamerlCmrsinCre o 5 2-Ft Dia 2- tFt -ia 4 ~6-ft Dia 0.75 47Il " - Ft13-4 iaa U +1.77 M...N .S.)2Is- Ol = X’Scot ,60O DLe4" e~~eoo Cnmlat~V~ aDxftcil Iffc /idaN 6-ft Die - 900 Bo 2-31S FtO ria LS135. 4- Dia60pi8fDa +oo 2:U13ý0 * X𔃼

The key role of growth hormone — insulin — IGF-1 signaling in aging and cancer

PubMed Central

Anisimov, Vladimir N.; Bartke, Andrzej

2014-01-01

Studies in mammals have led to the suggestion that hyperglycemia and hyperinsulinemia are important factors in aging. GH/Insulin/insulin-like growth factor 1 (IGF-1) signaling molecules that have been linked to longevity include daf-2 and InR and their homologues in mammals, and inactivation of the corresponding genes increases lifespan in nematodes, fruit flies and mice. The life-prolonging effects of caloric restriction are likely related to decreasing IGF-1 levels. Evidence has emerged that antidiabetic drugs are promising candidates for both lifespan extension and prevention of cancer. Thus, antidiabetic drugs postpone spontaneous carcinogenesis in mice and rats, as well as chemical and radiation carcinogenesis in mice, rats and hamsters. Furthermore, metformin seems to decrease the risk for cancer in diabetic patients. PMID:23434537

Prediction of dimethyl disulfide levels from biosolids using statistical modeling.

PubMed

Gabriel, Steven A; Vilalai, Sirapong; Arispe, Susanna; Kim, Hyunook; McConnell, Laura L; Torrents, Alba; Peot, Christopher; Ramirez, Mark

2005-01-01

Two statistical models were used to predict the concentration of dimethyl disulfide (DMDS) released from biosolids produced by an advanced wastewater treatment plant (WWTP) located in Washington, DC, USA. The plant concentrates sludge from primary sedimentation basins in gravity thickeners (GT) and sludge from secondary sedimentation basins in dissolved air flotation (DAF) thickeners. The thickened sludge is pumped into blending tanks and then fed into centrifuges for dewatering. The dewatered sludge is then conditioned with lime before trucking out from the plant. DMDS, along with other volatile sulfur and nitrogen-containing chemicals, is known to contribute to biosolids odors. These models identified oxidation/reduction potential (ORP) values of a GT and DAF, the amount of sludge dewatered by centrifuges, and the blend ratio between GT thickened sludge and DAF thickened sludge in blending tanks as control variables. The accuracy of the developed regression models was evaluated by checking the adjusted R2 of the regression as well as the signs of coefficients associated with each variable. In general, both models explained observed DMDS levels in sludge headspace samples. The adjusted R2 value of the regression models 1 and 2 were 0.79 and 0.77, respectively. Coefficients for each regression model also had the correct sign. Using the developed models, plant operators can adjust the controllable variables to proactively decrease this odorant. Therefore, these models are a useful tool in biosolids management at WWTPs.

Flotation of algae for water reuse and biomass production: role of zeta potential and surfactant to separate algal particles.

PubMed

Kwak, Dong-Heui; Kim, Mi-Sug

2015-01-01

The effect of chemical coagulation and biological auto-flocculation relative to zeta potential was examined to compare flotation and sedimentation separation processes for algae harvesting. Experiments revealed that microalgae separation is related to auto-flocculation of Anabaena spp. and requires chemical coagulation for the whole period of microalgae cultivation. In addition, microalgae separation characteristics which are associated with surfactants demonstrated optimal microalgae cultivation time and separation efficiency of dissolved CO2 flotation (DCF) as an alternative to dissolved air flotation (DAF). Microalgae were significantly separated in response to anionic surfactant rather than cationic surfactant as a function of bubble size and zeta potential. DAF and DCF both showed slightly efficient flotation; however, application of anionic surfactant was required when using DCF.

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

PubMed

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.

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

NASA Astrophysics Data System (ADS)

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.

Real-time electrochemical detection of extracellular nitric oxide in tobacco cells exposed to cryptogein, an elicitor of defence responses

PubMed Central

Besson-Bard, Angélique; Griveau, Sophie; Bedioui, Fethi; Wendehenne, David

2008-01-01

It was previously reported that cryptogein, an elicitor of defence responses, induces an intracellular production of nitric oxide (NO) in tobacco. Here, the possibility was explored that cryptogein might also trigger an increase of NO extracellular content through two distinct approaches, an indirect method using the NO probe 4,5-diaminofluorescein (DAF-2) and an electrochemical method involving a chemically modified microelectrode probing free NO in biological media. While the chemical nature of DAF-2-reactive compound(s) is still uncertain, the electrochemical modified microelectrodes provide real-time evidence that cryptogein induces an increase of extracellular NO. Direct measurement of free extracellular NO might offer important new insights into its role in plants challenged by biotic stresses. PMID:18653691

Late Noachian and early Hesperian ridge systems in the south circumpolar Dorsa Argentea Formation, Mars: Evidence for two stages of melting of an extensive late Noachian ice sheet

NASA Astrophysics Data System (ADS)

Kress, Ailish M.; Head, James W.

2015-05-01

The Dorsa Argentea Formation (DAF), extending from 270°-100° E and 70°-90° S, is a huge circumpolar deposit surrounding and underlying the Late Amazonian South Polar Layered Deposits (SPLD) of Mars. Currently mapped as Early-Late Hesperian in age, the Dorsa Argentea Formation has been interpreted as volatile-rich, possibly representing the remnants of an ancient polar ice cap. Uncertain are its age (due to the possibility of poor crater retention in ice-related deposits), its mode of origin, the origin of the distinctive sinuous ridges and cavi that characterize the unit, and its significance in the climate history of Mars. In order to assess the age of activity associated with the DAF, we examined the ridge populations within the Dorsa Argentea Formation, mapping and characterizing seven different ridge systems (composed of nearly 4,000 ridges covering a total area of ~300,000 km2, with a cumulative length of ridges of ~51,000 km) and performing crater counts on them using the method of buffered crater counting to determine crater retention ages of the ridge populations. We examined the major characteristics of the ridge systems and found that the majority of them were consistent with an origin as eskers, sediment-filled subglacial drainage channels. Ridge morphologies reflect both distributed and channelized esker systems, and evidence is also seen that some ridges form looping moraine-like termini distal to some distributed systems. The ridge populations fall into two age groups: ridge systems between 270° and 0° E date to the Early Hesperian, but to the east, the Promethei Planum and the Chasmata ridge systems date to the Late Noachian. Thus, these ages, and esker and moraine-like morphologies, support the interpretation that the DAF is a remnant ice sheet deposit, and that the esker systems represent evidence of significant melting and drainage of meltwater from portions of this ice sheet, thus indicating at least some regions and/or periods of wet-based glaciation. The Late Noachian and Early Hesperian ages of the ridge systems closely correspond to the ages of valley network/open basin lake systems, representing runoff, drainage and storage of liquid water in non-polar regions of the surface of Mars. Potential causes of such wet-based conditions in the DAF include: 1) top-down melting due to atmospheric warming, 2) enhanced snow and ice accumulation and raising of the melting isotherm to the base of the ice sheet, or 3) basal melting associated with intrusive volcanism (volcano-ice interactions). The early phase of melting is closely correlated in time with valley network formation and thus may be due to global atmospheric warming, while the later phase of melting may be linked to Early Hesperian global volcanism and specific volcano-ice interactions (table mountains) in the DAF. Crater ages indicate that these wet-based conditions ceased by the Late Hesperian, and that further retreat of the DAF to its present configuration occurred largely through sublimation, not melting, thus preserving the extensive ridge systems. MARSIS radar data suggest that significant areas of layered, potentially ice-rich parts of the Dorsa Argentea Formation remain today.

Knock-out of a mitochondrial sirtuin protects neurons from degeneration in Caenorhabditis elegans

PubMed Central

Sangaletti, Rachele; Grant, Jeff; Della-Morte, David

2017-01-01

Sirtuins are NAD⁺-dependent deacetylases, lipoamidases, and ADP-ribosyltransferases that link cellular metabolism to multiple intracellular pathways that influence processes as diverse as cell survival, longevity, and cancer growth. Sirtuins influence the extent of neuronal death in stroke. However, different sirtuins appear to have opposite roles in neuronal protection. In Caenorhabditis elegans, we found that knock-out of mitochondrial sirtuin sir-2.3, homologous to mammalian SIRT4, is protective in both chemical ischemia and hyperactive channel induced necrosis. Furthermore, the protective effect of sir-2.3 knock-out is enhanced by block of glycolysis and eliminated by a null mutation in daf-16/FOXO transcription factor, supporting the involvement of the insulin/IGF pathway. However, data in Caenorhabditis elegans cell culture suggest that the effects of sir-2.3 knock-out act downstream of the DAF-2/IGF-1 receptor. Analysis of ROS in sir-2.3 knock-out reveals that ROS become elevated in this mutant under ischemic conditions in dietary deprivation (DD), but to a lesser extent than in wild type, suggesting more robust activation of a ROS scavenging system in this mutant in the absence of food. This work suggests a deleterious role of SIRT4 during ischemic processes in mammals that must be further investigated and reveals a novel pathway that can be targeted for the design of therapies aimed at protecting neurons from death in ischemic conditions. PMID:28820880

Case report and literature review: transient Inab phenotype and an agglutinating anti-IFC in a patient with a gastrointestinal problem.

PubMed

Yazer, Mark H; Judd, W John; Davenport, Robertson D; Dake, Louann R; Lomas-Francis, Christine; Hue-Roye, Kim; Powell, Vivien; Reid, Marion

2006-09-01

The Inab phenotype is a rare deficiency of all Cromer antigens. These antigens are carried on the decay-accelerating factor (DAF, CD55) molecule that is attached to the red blood cell (RBC) membrane by a glycosylphosphatidylinositol (GPI) anchor. Although typically inherited, an acquired and transient form of the Inab phenotype also exists. A patient with the triad of transient Inab phenotype, a direct-agglutinating anti-IFC, and gastrointestinal (GI) abnormalities is reported. An 18-month-old boy with gastroesophageal reflux disease requiring a feeding tube, milk and soy intolerance, and severe growth retardation, as well as vision and hearing deficits from cytomegalovirus infection, was identified when pretransfusion testing revealed a potent panagglutinin (titer > 2000 at 4 degrees C). This antibody did not react with Dr(a-) and IFC RBCs, and the autocontrol was negative. The patient's RBCs lacked CD55 by flow cytometric techniques but had normal levels of CD59 and antigens such as Yt(a) and Emm, carried on GPI-linked proteins, thus excluding paroxysmal nocturnal hemoglobinuria. Several months after initial detection, the anti-IFC was virtually undetectable and his cells reacted weakly with anti-IFC, anti-Dr(a), and anti-CD55. RBCs from the propositus' parents and brother demonstrated normal CD55 and CD59 expression. This is the first example of a direct-agglutinating anti-IFC. The cause of the transient depression in CD55 protein (and thus Cromer system antigens) and appearance of anti-IFC remains unknown, as does the relationship between the patient's GI system abnormalities and these serologic findings.

Positive Feedback between Transcriptional and Kinase Suppression in Nematodes with Extraordinary Longevity and Stress Resistance

PubMed Central

Bharill, Puneet; Shmookler Reis, Robert J.

2009-01-01

Insulin/IGF-1 signaling (IIS) regulates development and metabolism, and modulates aging, of Caenorhabditis elegans. In nematodes, as in mammals, IIS is understood to operate through a kinase-phosphorylation cascade that inactivates the DAF-16/FOXO transcription factor. Situated at the center of this pathway, phosphatidylinositol 3-kinase (PI3K) phosphorylates PIP2 to form PIP3, a phospholipid required for membrane tethering and activation of many signaling molecules. Nonsense mutants of age-1, the nematode gene encoding the class-I catalytic subunit of PI3K, produce only a truncated protein lacking the kinase domain, and yet confer 10-fold greater longevity on second-generation (F2) homozygotes, and comparable gains in stress resistance. Their F1 parents, like weaker age-1 mutants, are far less robust—implying that maternally contributed trace amounts of PI3K activity or of PIP3 block the extreme age-1 phenotypes. We find that F2-mutant adults have <10% of wild-type kinase activity in vitro and <60% of normal phosphoprotein levels in vivo. Inactivation of PI3K not only disrupts PIP3-dependent kinase signaling, but surprisingly also attenuates transcripts of numerous IIS components, even upstream of PI3K, and those of signaling molecules that cross-talk with IIS. The age-1(mg44) nonsense mutation results, in F2 adults, in changes to kinase profiles and to expression levels of multiple transcripts that distinguish this mutant from F1 age-1 homozygotes, a weaker age-1 mutant, or wild-type adults. Most but not all of those changes are reversed by a second mutation to daf-16, implicating both DAF-16/ FOXO–dependent and –independent mechanisms. RNAi, silencing genes that are downregulated in long-lived worms, improves oxidative-stress resistance of wild-type adults. It is therefore plausible that attenuation of those genes in age-1(mg44)-F2 adults contributes to their exceptional survival. IIS in nematodes (and presumably in other species) thus involves transcriptional as well as kinase regulation in a positive-feedback circuit, favoring either survival or reproduction. Hyperlongevity of strong age-1(mg44) mutants may result from their inability to reset this molecular switch to the reproductive mode. PMID:19360094

Identification of phenolic secondary metabolites from Schotia brachypetala Sond. (Fabaceae) and demonstration of their antioxidant activities in Caenorhabditis elegans

PubMed Central

Labib, Rola M.; Handoussa, Heba; Swilam, Noha; El-Khatib, Ahmed H.; Sharapov, Farukh; Mohamed, Tamer; Krstin, Sonja; Linscheid, Michael W.; Singab, Abdel Nasser; Wink, Michael

2016-01-01

Background Schotia brachypetala Sond. (Fabaceae) is an endemic tree of Southern Africa whose phytochemistry and pharmacology were slightly studied. The present work aimed at profiling the major phenolics compounds present in the hydro-alcohol extract from S. brachypetala leaves (SBE) using LC/HRESI/MS/MS and NMR and prove their antioxidant capabilities using novel methods. Methods In vitro assays; DPPH, TEAC persulfate decolorizing kinetic and FRAP assays, and in vivo assays: Caenorhabditis elegans strains maintenance, Intracellular ROS in C. elegans, Survival assay, GFP expression and Subcellular DAF-16 localization were employed to evaluate the antioxidant activity. Results More than forty polyphenols, including flavonoid glycosides, galloylated flavonoid glycosides, isoflavones, dihydrochalcones, procyanidins, anthocyanins, hydroxy benzoic acid derivatives, hydrolysable tannins, and traces of methylated and acetylated flavonoid derivatives were identified. Three compounds were isolated and identified from the genus Schotia for the first time, namely gallic acid, myricetin-3-O-α-L-1C4-rhamnoside and quercetin-3-O-L-1C4-rhamnoside. The total phenolics content of SBE was (376 mg CAE/g), followed by flavonoids (67.87 QE/g). In vitro antioxidant activity of SBE was evidenced by DPPH radical scavenging activity (IC50 of 9 µg/mL), FRAP ferric reducing activity (5,000 mol Fe2+ E/mg) and ABTS peroxide inhibiting activity (1,054 mM Trolox E/mg). The tested extract was able to protect the worms against juglone induced oxidative stress, an increased survival rate (up to 41%) was recorded, when compared with the control group (11%) and attenuate the reactive oxygen species (ROS) accumulation in dose-dependent and reached up to 72% for the highest tested concentration. SBE was also able to attenuate the levels of heat shock protein (HSP) expression in dose-dependent up to 60% in the 150 µg SBE/mL group. In DAF-16 Subcellular localization SBE treated worms showed nuclear localization pattern up to 78%, while it was only 5% in the untreated control group. Discussion A pronounced antioxidant activity in vivo, which can be attributed to its ability to promote the nuclear translocation of DAF-16/FOXO, the main transcription factor regulating the expression of stress response genes. The remarkable antioxidant activity in vitro and in vivo correlates to SBE rich phenolic profile. PMID:27896020

Oxaloacetate supplementation increases lifespan in Caenorhabditis elegans through an AMPK/FOXO-dependent pathway

PubMed Central

Williams, David S.; Cash, Alan; Hamadani, Lara; Diemer, Tanja

2010-01-01

Summary Reduced dietary intake increases lifespan in a wide variety of organisms. It also retards disease progression. We tested whether dietary supplementation of citric acid cycle metabolites could mimic this lifespan effect. We report that oxaloacetate supplementation increased lifespan in Caenorhabditis elegans. The increase was dependent on the transcription factor, FOXO/DAF-16, and the energy sensor, AMP-activated protein kinase, indicating involvement of a pathway that is also required for lifespan extension through dietary restriction. These results demonstrate that supplementation of the citric acid cycle metabolite, oxaloacetate, influences a longevity pathway, and suggest a tractable means of introducing the health-related benefits of dietary restriction. PMID:19793063

Bacillus subtilis biofilm extends Caenorhabditis elegans longevity through downregulation of the insulin-like signalling pathway

PubMed Central

Donato, Verónica; Ayala, Facundo Rodríguez; Cogliati, Sebastián; Bauman, Carlos; Costa, Juan Gabriel; Leñini, Cecilia; Grau, Roberto

2017-01-01

Beneficial bacteria have been shown to affect host longevity, but the molecular mechanisms mediating such effects remain largely unclear. Here we show that formation of Bacillus subtilis biofilms increases Caenorhabditis elegans lifespan. Biofilm-proficient B. subtilis colonizes the C. elegans gut and extends worm lifespan more than biofilm-deficient isogenic strains. Two molecules produced by B. subtilis — the quorum-sensing pentapeptide CSF and nitric oxide (NO) — are sufficient to extend C. elegans longevity. When B. subtilis is cultured under biofilm-supporting conditions, the synthesis of NO and CSF is increased in comparison with their production under planktonic growth conditions. We further show that the prolongevity effect of B. subtilis biofilms depends on the DAF-2/DAF-16/HSF-1 signalling axis and the downregulation of the insulin-like signalling (ILS) pathway. PMID:28134244

Trehalose extends longevity in the nematode Caenorhabditis elegans.

PubMed

Honda, Yoko; Tanaka, Masashi; Honda, Shuji

2010-08-01

Trehalose is a disaccharide of glucose found in diverse organisms and is suggested to act as a stress protectant against heat, cold, desiccation, anoxia, and oxidation. Here, we demonstrate that treatment of Caenorhabditis elegans with trehalose starting from the young-adult stage extended the mean life span by over 30% without any side effects. Surprisingly, trehalose treatment starting even from the old-adult stage shortly thereafter retarded the age-associated decline in survivorship and extended the remaining life span by 60%. Demographic analyses of age-specific mortality rates revealed that trehalose extended the life span by lowering age-independent vulnerability. Moreover, trehalose increased the reproductive span and retarded the age-associated decrease in pharyngeal-pumping rate and the accumulation of lipofuscin autofluorescence. Trehalose also enhanced thermotolerance and reduced polyglutamine aggregation. These results suggest that trehalose suppressed aging by counteracting internal or external stresses that disrupt protein homeostasis. On the other hand, the life span-extending effect of trehalose was abolished in long-lived insulin/IGF-1-like receptor (daf-2) mutants. RNA interference-mediated inactivation of the trehalose-biosynthesis genes trehalose-6-phosphate synthase-1 (tps-1) and tps-2, which are known to be up-regulated in daf-2 mutants, decreased the daf-2 life span. These findings indicate that a reduction in insulin/IGF-1-like signaling extends life span, at least in part, through the aging-suppressor function of trehalose. Trehalose may be a lead compound for potential nutraceutical intervention of the aging process.

Long-Range Regulatory Polymorphisms Affecting a GABA Receptor Constitute a Quantitative Trait Locus (QTL) for Social Behavior in Caenorhabditis elegans

PubMed Central

Bendesky, Andres; Pitts, Jason; Rockman, Matthew V.; Chen, William C.; Tan, Man-Wah; Kruglyak, Leonid; Bargmann, Cornelia I.

2012-01-01

Aggregation is a social behavior that varies between and within species, providing a model to study the genetic basis of behavioral diversity. In the nematode Caenorhabditis elegans, aggregation is regulated by environmental context and by two neuromodulatory pathways, one dependent on the neuropeptide receptor NPR-1 and one dependent on the TGF-β family protein DAF-7. To gain further insight into the genetic regulation of aggregation, we characterize natural variation underlying behavioral differences between two wild-type C. elegans strains, N2 and CB4856. Using quantitative genetic techniques, including a survey of chromosome substitution strains and QTL analysis of recombinant inbred lines, we identify three new QTLs affecting aggregation in addition to the two known N2 mutations in npr-1 and glb-5. Fine-mapping with near-isogenic lines localized one QTL, accounting for 5%–8% of the behavioral variance between N2 and CB4856, 3′ to the transcript of the GABA neurotransmitter receptor gene exp-1. Quantitative complementation tests demonstrated that this QTL affects exp-1, identifying exp-1 and GABA signaling as new regulators of aggregation. exp-1 interacts genetically with the daf-7 TGF-β pathway, which integrates food availability and population density, and exp-1 mutations affect the level of daf-7 expression. Our results add to growing evidence that genetic variation affecting neurotransmitter receptor genes is a source of natural behavioral variation. PMID:23284308

Treatment of drinking water residuals: comparing sedimentation and dissolved air flotation performance with optimal cation ratios.

PubMed

Bourgeois, J C; Walsh, M E; Gagnon, G A

2004-03-01

Spent filter backwash water (SFBW) and clarifier sludge generally comprise the majority of the waste residual volume generated and in relative terms, these can be collectively referred to as combined filter backwash water (CFBW). CFBW is essentially a low-solids wastewater with metal hydroxide flocs that are typically light and slow to settle. This study evaluates the impact of adding calcium and magnesium carbonates to CFBW in terms of assessing the impacts on the sedimentation and DAF separation processes. Representative CFBW samples were collected from two surface water treatment plants (WTP): Lake Major WTP (Dartmouth, Nova Scotia, Canada) and Victoria Park WTP (Truro, Nova Scotia, Canada). Bench-scale results indicated that improvements in the CFBW settled water quality could be achieved through the addition of the divalent cations, thereby adjusting the monovalent to divalent (M:D) ratios of the wastewater. In general, the DAF process required slightly higher M:D ratios than the sedimentation process. The optimum M:D ratios for DAF and sedimentation were determined to be 1:1 and 0.33:1, respectively. It was concluded that the optimisation of the cation balance between monovalent cations (e.g., Na(+), K(+)) and added divalent cations (i.e., Ca(2+), Mg(2+)) aided in the settling mechanism through charge neutralisation-precipitation. The increase in divalent cation concentrations within the waste residual stream promoted destabilisation of the negatively charged colour molecules within the CFBW, thereby causing the colloidal content to become more hydrophobic.

ARCHITECT: The architecture-based technology evaluation and capability tradeoff method

NASA Astrophysics Data System (ADS)

Griendling, Kelly A.

The use of architectures for the design, development, and documentation of system-of-systems engineering has become a common practice in recent years. This practice became mandatory in the defense industry in 2004 when the Department of Defense Architecture Framework (DoDAF) Promulgation Memo mandated that all Department of Defense (DoD) architectures must be DoDAF compliant. Despite this mandate, there has been significant confusion and a lack of consistency in the creation and the use of the architecture products. Products are typically created as static documents used for communication and documentation purposes that are difficult to change and do not support engineering design activities and acquisition decision making. At the same time, acquisition guidance has been recently reformed to move from the bottom-up approach of the Requirements Generation System (RGS) to the top-down approach mandated by the Joint Capabilities Integration and Devel- opment System (JCIDS), which requires the use of DoDAF to support acquisition. Defense agencies have had difficulty adjusting to this new policy, and are struggling to determine how to meet new acquisition requirements. This research has developed the Architecture-based Technology Evaluation and Capability Tradeoff (ARCHITECT) Methodology to respond to these challenges and address concerns raised about the defense acquisition process, particularly the time required to implement parts of the process, the need to evaluate solutions across capability and mission areas, and the need to use a rigorous, traceable, repeatable method that utilizes modeling and simulation to better substantiate early-phase acquisition decisions. The objective is to create a capability-based systems engineering methodology for the early phases of design and acquisition (specifically Pre-Milestone A activities) which improves agility in defense acquisition by (1) streamlining the development of key elements of JCIDS and DoDAF, (2) moving the creation of DoDAF products forward in the defense acquisition process, and (3) using DoDAF products for more than documentation by integrating them into the problem definition and analysis of alternatives phases and applying executable architecting. This research proposes and demonstrates the plausibility of a prescriptive methodology for developing executable DoDAF products which will explicitly support decision-making in the early phases of JCIDS. A set of criteria by which CBAs should be judged is proposed, and the methodology is developed with these criteria in mind. The methodology integrates existing tools and techniques for systems engineering and system of systems engineering with several new modeling and simulation tools and techniques developed as part of this research to fill gaps noted in prior CBAs. A suppression of enemy air defenses (SEAD) mission is used to demonstrate the ap- plication of ARCHITECT and to show the plausibility of the approach. For the SEAD study, metrics are derived and a gap analysis is performed. The study then identifies and quantitatively compares system and operational architecture alternatives for performing SEAD. A series of down-selections is performed to identify promising architectures, and these promising solutions are subject to further analysis where the impacts of force structure and network structure are examined. While the numerical results of the SEAD study are notional and could not be applied to an actual SEAD CBA, the example served to highlight many of the salient features of the methodology. The SEAD study presented enabled pre-Milestone A tradeoffs to be performed quantitatively across a large number of architectural alternatives in a traceable and repeatable manner. The alternatives considered included variations on operations, systems, organizational responsibilities (through the assignment of systems to tasks), network (or collaboration) structure, interoperability level, and force structure. All of the information used in the study is preserved in the environment, which is dynamic and allows for on-the-fly analysis. The assumptions used were consistent, which was assured through the use of single file documenting all inputs, which was shared across all models. Furthermore, a model was made of the ARCHITECT methodology itself, and was used to demonstrate that even if the steps took twice as long to perform as they did in the case of the SEAD example, the methodology still provides the ability to conduct CBA analyses in less time than prior CBAs to date. Overall, it is shown that the ARCHITECT methodology results in an improvement over current CBAs in the criteria developed here.

Dauer-independent insulin/IGF-1-signalling implicates collagen remodelling in longevity.

PubMed

Ewald, Collin Y; Landis, Jess N; Porter Abate, Jess; Murphy, Coleen T; Blackwell, T Keith

2015-03-05

Interventions that delay ageing mobilize mechanisms that protect and repair cellular components, but it is unknown how these interventions might slow the functional decline of extracellular matrices, which are also damaged during ageing. Reduced insulin/IGF-1 signalling (rIIS) extends lifespan across the evolutionary spectrum, and in juvenile Caenorhabditis elegans also allows the transcription factor DAF-16/FOXO to induce development into dauer, a diapause that withstands harsh conditions. It has been suggested that rIIS delays C. elegans ageing through activation of dauer-related processes during adulthood, but some rIIS conditions confer robust lifespan extension unaccompanied by any dauer-like traits. Here we show that rIIS can promote C. elegans longevity through a program that is genetically distinct from the dauer pathway, and requires the Nrf (NF-E2-related factor) orthologue SKN-1 acting in parallel to DAF-16. SKN-1 is inhibited by IIS and has been broadly implicated in longevity, but is rendered dispensable for rIIS lifespan extension by even mild activity of dauer-related processes. When IIS is decreased under conditions that do not induce dauer traits, SKN-1 most prominently increases expression of collagens and other extracellular matrix genes. Diverse genetic, nutritional, and pharmacological pro-longevity interventions delay an age-related decline in collagen expression. These collagens mediate adulthood extracellular matrix remodelling, and are needed for ageing to be delayed by interventions that do not involve dauer traits. By genetically delineating a dauer-independent rIIS ageing pathway, our results show that IIS controls a broad set of protective mechanisms during C. elegans adulthood, and may facilitate elucidation of processes of general importance for longevity. The importance of collagen production in diverse anti-ageing interventions implies that extracellular matrix remodelling is a generally essential signature of longevity assurance, and that agents promoting extracellular matrix youthfulness may have systemic benefit.

A Novel 3-Hydroxysteroid Dehydrogenase That Regulates Reproductive Development and Longevity

PubMed Central

Wollam, Joshua; Magner, Daniel B.; Magomedova, Lilia; Rass, Elisabeth; Shen, Yidong; Rottiers, Veerle; Habermann, Bianca; Cummins, Carolyn L.; Antebi, Adam

2012-01-01

Endogenous small molecule metabolites that regulate animal longevity are emerging as a novel means to influence health and life span. In C. elegans, bile acid-like steroids called the dafachronic acids (DAs) regulate developmental timing and longevity through the conserved nuclear hormone receptor DAF-12, a homolog of mammalian sterol-regulated receptors LXR and FXR. Using metabolic genetics, mass spectrometry, and biochemical approaches, we identify new activities in DA biosynthesis and characterize an evolutionarily conserved short chain dehydrogenase, DHS-16, as a novel 3-hydroxysteroid dehydrogenase. Through regulation of DA production, DHS-16 controls DAF-12 activity governing longevity in response to signals from the gonad. Our elucidation of C. elegans bile acid biosynthetic pathways reveals the possibility of novel ligands as well as striking biochemical conservation to other animals, which could illuminate new targets for manipulating longevity in metazoans. PMID:22505847

Evaluation of flow hydrodynamics in a pilot-scale dissolved air flotation tank: a comparison between CFD and experimental measurements.

PubMed

Lakghomi, B; Lawryshyn, Y; Hofmann, R

2015-01-01

Computational fluid dynamics (CFD) models of dissolved air flotation (DAF) have shown formation of stratified flow (back and forth horizontal flow layers at the top of the separation zone) and its impact on improved DAF efficiency. However, there has been a lack of experimental validation of CFD predictions, especially in the presence of solid particles. In this work, for the first time, both two-phase (air-water) and three-phase (air-water-solid particles) CFD models were evaluated at pilot scale using measurements of residence time distribution, bubble layer position and bubble-particle contact efficiency. The pilot-scale results confirmed the accuracy of the CFD model for both two-phase and three-phase flows, but showed that the accuracy of the three-phase CFD model would partly depend on the estimation of bubble-particle attachment efficiency.

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

Dhondt, Ineke; Petyuk, Vladislav A.; Cai, Huaihan

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. But, 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. We found that this slowdown wasmore » most prominent for translation-related and mitochondrial proteins. Conversely, 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.« less

Chemosensation of Bacterial Secondary Metabolites Modulates Neuroendocrine Signaling and Behavior of C. elegans

PubMed Central

Meisel, Joshua D.; Panda, Oishika; Mahanti, Parag; Schroeder, Frank C.; Kim, Dennis H.

2014-01-01

Summary Discrimination among pathogenic and beneficial microbes is essential for host organism immunity and homeostasis. Here, we show that chemosensory detection of two secondary metabolites produced by Pseudomonas aeruginosa modulates a neuroendocrine signaling pathway that promotes avoidance behavior in the simple animal host Caenorhabditis elegans. Secondary metabolites phenazine-1-carboxamide and pyochelin activate a G protein-signaling pathway in the ASJ chemosensory neuron pair that induces expression of the neuromodulator DAF-7/TGF-β. DAF-7, in turn, activates a canonical TGF-β signaling pathway in adjacent interneurons to modulate aerotaxis behavior and promote avoidance of pathogenic P. aeruginosa. Our data provide a chemical, genetic, and neuronal basis for how the behavior and physiology of a simple animal host can be modified by the microbial environment, and suggest that secondary metabolites produced by microbes may provide environmental cues that contribute to pathogen recognition and host survival. PMID:25303524

Effect of adsorbent addition on floc formation and clarification.

PubMed

Younker, Jessica M; Walsh, Margaret E

2016-07-01

Adding adsorbent into the coagulation process is an emerging treatment solution for targeting hard-to-remove dissolved organic compounds from both drinking water and industrial wastewater. The impact of adding powdered activated carbon (PAC) or organoclay (OC) adsorbents with ferric chloride (FeCl3) coagulant was investigated in terms of potential changes to the coagulated flocs formed with respect to size, structure, and breakage and regrowth properties. The ability of dissolved air flotation (DAF) and sedimentation (SED) clarification processes to remove hybrid adsorbent-coagulant flocs was also evaluated through clarified water quality analysis of samples collected in bench-scale jar test experiments. The jar tests were conducted using both a synthetic fresh water and oily wastewater test water spiked with dissolved aromatic compounds phenol and naphthalene. Results of the study demonstrated that addition of adsorbent reduced the median coagulated floc size by up to 50% but did not affect floc strength or regrowth potential after application of high shear. Experimental results in fresh water demonstrated that sedimentation was more effective than DAF for clarification of both FeCl3-PAC and FeCl3-OC floc aggregates. However, experimental tests performed on the synthetic oily wastewater showed that coagulant-adsorbent floc aggregates were effectively removed with both DAF and sedimentation treatment, with lower residual turbidity achieved in clarified water samples than with coagulation treatment alone. Addition of OC or PAC into the coagulation process resulted in removals of over half, or nearly all of the dissolved aromatics, respectively. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mutant Transcriptome Sequencing Provides Insights into Pod Development in Peanut (Arachis hypogaea L.)

PubMed Central

Wan, Liyun; Li, Bei; Lei, Yong; Yan, Liying; Ren, Xiaoping; Chen, Yuning; Dai, Xiaofeng; Jiang, Huifang; Zhang, Juncheng; Guo, Wei; Chen, Ao; Liao, Boshou

2017-01-01

Pod size is the major yield component and a key target trait that is selected for in peanut breeding. However, although numerous quantitative trait loci (QTLs) for peanut pod size have been described, the molecular mechanisms underlying the development of this characteristic remain elusive. A peanut mutant with a narrower pod was developed in this study using ethyl methanesulfonate (EMS) mutagenesis and designated as the “pod width” mutant line (pw). The fresh pod weight of pw was only about 40% of that seen in the wild-type (WT) Zhonghua16, while the hull and seed filling of the mutant both also developed at earlier stages. Pods from both pw and WT lines were sampled 20, 40, and 60 days after flowering (DAF) and used for RNA-Seq analysis; the results revealed highly differentially expressed lignin metabolic pathway genes at all three stages, but especially at DAF 20 and DAF 40. At the same time, expression of genes related to auxin signal transduction was found to be significantly repressed during the pw early pod developmental stage. A genome-wide comparative analysis of expression profiles revealed 260 differentially expressed genes (DEGs) across all three stages, and two candidate genes, c26901_g1 (CAD) and c37339_g1 (ACS), responsible for pod width were identified by integrating expression patterns and function annotation of the common DEGs within the three stages. Taken together, the information provided in this study illuminates the processes underlying peanut pod development, and will facilitate further identification of causal genes and the development of improved peanut varieties with higher yields. PMID:29170673

Agrometeorological parameters for prediction of the maturation period of Arabica coffee cultivars

NASA Astrophysics Data System (ADS)

Pezzopane, José Ricardo Macedo; Salva, Terezinha de Jesus Garcia; de Lima, Valéria Bittencourt; Fazuoli, Luiz Carlos

2012-09-01

The objective of this study was to determine the harvest period of coffee fruits based on the relationship between agrometeorological parameters and sucrose accumulation in the seeds. Over the crop years 2004/2005 and 2006/2007, from 150 days after flowering (DAF) onwards, samples of 50 fruits of cultivars Mundo Novo IAC 376-4, Obatã IAC 1669-20 and Catuaí Vermelho IAC 144 were collected from coffee trees located in Campinas, Brazil. The endosperm of the fruits was freeze-dried, ground and analyzed for sucrose content by high-performance liquid chromatography. A weather station provided data to calculate the accumulated growing degree-day (GDD) units, and the reference (ETo) and actual (ETr) evapotranspiration rates. The results showed that the highest rates of sucrose accumulation occurred at the transition from the cane-green to the cherry phenological stage. Models for the estimation of sucrose content during maturation based on meteorological variables exhibited similar or better performance than the DAF variable, with better results for the variables GDD and ETo. The Mundo Novo cultivar reached the highest sucrose level in the endosperm after 2,790 GDD, while cultivar Catuaí attained its maximum sucrose concentration after the accumulated evapotranspiration rate has reached a value of 870 mm. As for cultivar Obatã, the maximum sucrose concentration was predicted with the same degree of accuracy using any of the parameters investigated. For the Obatã cultivar, the values of the variables calculated for the maximum sucrose concentration to be reached were 249 DAF, 3,090 GDD, 1,020 ETo and 900 ETr.

Maple Syrup Decreases TDP-43 Proteotoxicity in a Caenorhabditis elegans Model of Amyotrophic Lateral Sclerosis (ALS).

PubMed

Aaron, Catherine; Beaudry, Gabrielle; Parker, J Alex; Therrien, Martine

2016-05-04

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease causing death of the motor neurons. Proteotoxicity caused by TDP-43 protein is an important aspect of ALS pathogenesis, with TDP-43 being the main constituent of the aggregates found in patients. We have previously tested the effect of different sugars on the proteotoxicity caused by the expression of mutant TDP-43 in Caenorhabditis elegans. Here we tested maple syrup, a natural compound containing many active molecules including sugars and phenols, for neuroprotective activity. Maple syrup decreased several age-dependent phenotypes caused by the expression of TDP-43(A315T) in C. elegans motor neurons and requires the FOXO transcription factor DAF-16 to be effective.

Mutation of C. elegans demethylase spr-5 extends transgenerational longevity

PubMed Central

Greer, Eric Lieberman; Becker, Ben; Latza, Christian; Antebi, Adam; Shi, Yang

2016-01-01

Complex organismal properties such as longevity can be transmitted across generations by non-genetic factors. Here we demonstrate that deletion of the C. elegans histone H3 lysine 4 dimethyl (H3K4me2) demethylase, spr-5, causes a trans-generational increase in lifespan. We identify a chromatin-modifying network, which regulates this lifespan extension. We further show that this trans-generational lifespan extension is dependent on a hormonal signaling pathway involving the steroid dafachronic acid, an activator of the nuclear receptor DAF-12. These findings suggest that loss of the demethylase SPR-5 causes H3K4me2 mis-regulation and activation of a known lifespan-regulating signaling pathway, leading to trans-generational lifespan extension. PMID:26691751

Reactive oxygen species regulate programmed cell death progress of endosperm in winter wheat (Triticum aestivum L.) under waterlogging.

PubMed

Cheng, Xiang-Xu; Yu, Min; Zhang, Nan; Zhou, Zhu-Qing; Xu, Qiu-Tao; Mei, Fang-Zhu; Qu, Liang-Huan

2016-03-01

Previous studies have proved that waterlogging stress accelerates the programmed cell death (PCD) progress of wheat endosperm cells. A highly waterlogging-tolerant wheat cultivar Hua 8 and a waterlogging susceptible wheat cultivar Hua 9 were treated with different waterlogging durations, and then, dynamic changes of reactive oxygen species (ROS), gene expressions, and activities of antioxidant enzymes in endosperm cells were detected. The accumulation of ROS increased considerably after 7 days of waterlogging treatment (7 DWT) and 12 DWT in both cultivars compared with control group (under non-waterlogged conditions), culminated at 12 DAF (days after flowering) and reduced hereafter. Waterlogging resulted in a great increase of H2O2 and O2 (-) in plasma membranes, cell walls, mitochondrias, and intercellular spaces with ultracytochemical localization. Moreover, the deformation and rupture of cytomembranes as well as the swelling and distortion of mitochondria were obvious. Under waterlogging treatment conditions, catalase (CAT) gene expression increased in endosperm of Hua 8 but activity decreased. In addition, Mn superoxide dismutase (MnSOD) gene expression and superoxide dismutase (SOD) activity increased. Compared with Hua 8, both CAT, MnSOD gene expressions and CAT, SOD activities decreased in Hua 9. Moreover, ascorbic acid and mannitol relieve the intensifying of PCD processes in Hua 8 endosperm cells induced by waterlogging. These results indicate that ROS have important roles in the PCD of endosperm cells, the changes both CAT, MnSOD gene expressions and CAT, SOD activities directly affected the accumulation of ROS in two different wheat cultivars under waterlogging, ultimately led to the PCD acceleration of endosperm.

75 FR 76444 - Environmental Impact Statement (EIS) for Construction and Operation of a Panoramic Survey...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-08

..., 3550 Aberdeen Ave., SE., Kirtland AFB, NM 87117- 5776 (Phone: 505-846-4321; e-mail [email protected]kirtland.af.mil ). Bao-Anh Trinh, GS-14, DAF, Air Force Federal Register Liaison Officer. [FR Doc. 2010...

75 FR 57686 - Hazardous Waste Management System; Identification and Listing of Hazardous Waste Amendment

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-22

... amending the exclusion for the American Steel Cord facility in Scottsburg, Indiana to reflect changes in...- calculated from the delisting health-based levels and a DAF of 68: arsenic-3.4; barium- 100; cadmium-0.34...

Human Spaceflight Architecture Model (HSFAM) Data Dictionary

NASA Technical Reports Server (NTRS)

Shishko, Robert

2016-01-01

HSFAM is a data model based on the DoDAF 2.02 data model with some for purpose extensions. These extensions are designed to permit quantitative analyses regarding stakeholder concerns about technical feasibility, configuration and interface issues, and budgetary and/or economic viability.

Integration of M&S (Modeling and Simulation), Software Design and DoDAF (Department of Defense Architecture Framework (RT 24)

DTIC Science & Technology

2012-04-09

between BPMN , SysML, and Arena ........................................... 16 Capabilities, Activities, Resources, Performers...Proof of Concept ................................................................ 22 BPMN 2.0 XML to Arena Converter...21 Figure 5: BPMN 2.0 XML StartEvent (Excerpt

Development of High-Throughput Method for Measurement of Vascular Nitric Oxide Generation in Microplate Reader.

PubMed

Abd El-Hay, Soad S; Colyer, Christa L

2017-01-13

Despite the importance of nitric oxide (NO) in vascular physiology and pathology, a high-throughput method for the quantification of its vascular generation is lacking. By using the fluorescent probe 4-amino-5-methylamino-2',7'-difluorofluorescein (DAF-FM), we have optimized a simple method for the determination of the generation of endothelial nitric oxide in a microplate format. A nitric oxide donor was used (3-morpholinosydnonimine hydrochloride, SIN-1). Different factors affecting the method were studied, such as the effects of dye concentration, different buffers, time of reaction, gain, and number of flashes. Beer's law was linear over a nanomolar range (1-10 nM) of SIN-1 with wavelengths of maximum excitation and emission at 495 and 525 nm; the limit of detection reached 0.897 nM. Under the optimized conditions, the generation of rat aortic endothelial NO was measured by incubating DAF-FM with serial concentrations (10-1000 µM) of acetylcholine (ACh) for 3 min. To confirm specificity, N ω -Nitro-l-arginine methyl ester (l-NAME)-the standard inhibitor of endothelial NO synthase-was found to inhibit the ACh-stimulated generation of NO. In addition, vessels pre-exposed for 1 h to 400 µM of the endothelial damaging agent methyl glyoxal showed inhibited NO generation when compared to the control stimulated by ACh. The capability of the method to measure micro-volume samples makes it convenient for the simultaneous handling of a very large number of samples. Additionally, it allows samples to be run simultaneously with their replicates to ensure identical experimental conditions, thus minimizing the effect of biological variability.

Effect of exogenous GA3 and its inhibitor paclobutrazol on floral formation, endogenous hormones, and flowering-associated genes in 'Fuji' apple (Malus domestica Borkh.).

PubMed

Zhang, Songwen; Zhang, Dong; Fan, Sheng; Du, Lisha; Shen, Yawen; Xing, Libo; Li, Youmei; Ma, Juanjuan; Han, Mingyu

2016-10-01

Gibberellins (GAs) reduce apple (Malus domestica) flowering rates; however, the mechanism of their action is not fully understood. To gain a better insight into gibberellin-regulated flowering, here, 5 year-old 'Fuji' apple trees were used to explore the responses of hormones [GA1+3, GA4+7, indole-3-acetic acid (IAA), zeatin-riboside (ZR), and abscisic acid (ABA)], and gibberellin- and flowering-associated genes, to applications of gibberellin acid (GA3) and paclobutrazol (PAC). Results showed that GA3 relatively stimulated vegetative growth and delayed floral induction. Moreover, GA3 spraying significantly affected contents of all endogenous hormones and all the genes tested in at least one time points: the content of endogenous GAs was increased instantly and that of ZR was reduced at 44 days after fullbloom (DAF), which might constitute an unfavorable factor for flower formation; MdKO (ent-kaurene oxidase gene) and MdGA20ox (GA20 oxidase gene) were significantly repressed by a high level of GAs through the negative feedback regulation of GA; additionally, the MdSPLs (SQUAMOSA-PROMOTER BINDING PROTEIN-LIKE) in this study were all significantly repressed by GA3 but promoted by PAC; the expression of MdFT1/2 (FLOWERING LOCUS T), MdSOC1 (SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1) and MdAP1 (APETALA1) in GA3-treated buds changed in the same way, and they were repressed at 44 DAF. We suppose that GA3 spraying disrupts the balance between ZR and GAs, and inhibits floral induction, probably by suppressing MdSPLs and the floral integrators in flower induction, which ultimately contributed to inhibiting flower formation. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Transcriptomic basis of functional difference and coordination between seeds and the silique wall of Brassica napus during the seed-filling stage.

PubMed

Liu, Han; Yang, Qingyong; Fan, Chuchuan; Zhao, Xiaoqin; Wang, Xuemin; Zhou, Yongming

2015-04-01

The silique of oilseed rape (Brassica napus) is a composite organ including seeds and the silique wall (SW) that possesses distinctly physiological, biochemical and functional differentiations. Yet, the molecular events controlling such differences between the SW and seeds, as well as their coordination during silique development at transcriptional level are largely unknown. Here, we identified large sets of differentially expressed genes in the SW and seeds of siliques at 21-22 days after flowering with a Brassica 95K EST microarray. At this particular stage, there were 3278 SW preferentially expressed genes and 2425 seed preferentially expressed genes. Using the MapMan visualization software, genes differentially regulated in various metabolic pathways and sub-pathways between the SW and seeds were revealed. Photosynthesis and transport-related genes were more actively transcripted in the SW, while those involved in lipid metabolism were more active in seeds during the seed filling stage. On the other hand, genes involved in secondary metabolisms were selectively regulated in the SW and seeds. Large numbers of transcription factors were identified to be differentially expressed between the SW and seeds, suggesting a complex pattern of transcriptional control in these two organs. Furthermore, most genes discussed in categories or pathways showed a similar expression pattern through 21 DAF to 42 DAF. Our results thus provide insights into the coordination of seeds and the SW in the developing silique at the transcriptional levels, which will facilitate the functional studies of important genes for improving B. napus seed productivity and quality. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Ozone inactivation of infectious prions in rendering plant and municipal wastewaters.

PubMed

Ding, Ning; Neumann, Norman F; Price, Luke M; Braithwaite, Shannon L; Balachandran, Aru; Belosevic, Miodrag; Gamal El-Din, Mohamed

2014-02-01

Disposal of tissues and organs associated with prion accumulation and infectivity in infected animals (designated as Specified Risk Materials [SRM]) is strictly regulated by the Canadian Food Inspection Agency (CFIA); however, the contamination of wastewater from slaughterhouses that handle SRM still poses public concern. In this study, we examined for the first time the partitioning of infectious prions in rendering plant wastewater and found that a large proportion of infectious prions were partitioned into the scum layer formed at the top after gravity separation, while quite a few infectious prions still remained in the wastewater. Subsequently, we assessed the ozone inactivation of infectious prions in the raw, natural gravity-separated and dissolved air flotation (DAF)-treated (i.e., primary-treated) rendering plant wastewater, and in a municipal final effluent (i.e., secondary-treated municipal wastewater). At applied ozone doses of 43.4-44.6 mg/L, ozone was instantaneously depleted in the raw rendering plant wastewater, while a greater than 4-log10 inactivation was achieved at a 5 min exposure in the DAF-treated rendering plant wastewater. Prion inactivation in the municipal final effluent was conducted with two levels of applied ozone doses of 13.4 and 22.5mg/L, and a greater than 4-log10 inactivation was achieved at a 5 min exposure with the higher ozone dose. Efficiency factor Hom (EFH) models were used to model (i.e., fit) the experimental data. The CT (disinfectant concentration multiplied by contact time) values were determined for 2- and 3-log10 inactivation in the municipal final effluent treated with an ozone dose of 13.4 mg/L. Our results indicate that ozone could serve as a final barrier for prion inactivation in primary- and/or secondary-treated wastewaters. © 2013.

Quantification of GC-biased gene conversion in the human genome

PubMed Central

Glémin, Sylvain; Arndt, Peter F.; Messer, Philipp W.; Petrov, Dmitri; Galtier, Nicolas; Duret, Laurent

2015-01-01

Much evidence indicates that GC-biased gene conversion (gBGC) has a major impact on the evolution of mammalian genomes. However, a detailed quantification of the process is still lacking. The strength of gBGC can be measured from the analysis of derived allele frequency spectra (DAF), but this approach is sensitive to a number of confounding factors. In particular, we show by simulations that the inference is pervasively affected by polymorphism polarization errors and by spatial heterogeneity in gBGC strength. We propose a new general method to quantify gBGC from DAF spectra, incorporating polarization errors, taking spatial heterogeneity into account, and jointly estimating mutation bias. Applying it to human polymorphism data from the 1000 Genomes Project, we show that the strength of gBGC does not differ between hypermutable CpG sites and non-CpG sites, suggesting that in humans gBGC is not caused by the base-excision repair machinery. Genome-wide, the intensity of gBGC is in the nearly neutral area. However, given that recombination occurs primarily within recombination hotspots, 1%–2% of the human genome is subject to strong gBGC. On average, gBGC is stronger in African than in non-African populations, reflecting differences in effective population sizes. However, due to more heterogeneous recombination landscapes, the fraction of the genome affected by strong gBGC is larger in non-African than in African populations. Given that the location of recombination hotspots evolves very rapidly, our analysis predicts that, in the long term, a large fraction of the genome is affected by short episodes of strong gBGC. PMID:25995268

Spatiotemporal alterations of cortical network activity by selective loss of NOS-expressing interneurons.

PubMed

Shlosberg, Dan; Buskila, Yossi; Abu-Ghanem, Yasmin; Amitai, Yael

2012-01-01

Deciphering the role of GABAergic neurons in large neuronal networks such as the neocortex forms a particularly complex task as they comprise a highly diverse population. The neuronal isoform of the enzyme nitric oxide synthase (nNOS) is expressed in the neocortex by specific subsets of GABAergic neurons. These neurons can be identified in live brain slices by the nitric oxide (NO) fluorescent indicator diaminofluorescein-2 diacetate (DAF-2DA). However, this indicator was found to be highly toxic to the stained neurons. We used this feature to induce acute phototoxic damage to NO-producing neurons in cortical slices, and measured subsequent alterations in parameters of cellular and network activity. Neocortical slices were briefly incubated in DAF-2DA and then illuminated through the 4× objective. Histochemistry for NADPH-diaphorase (NADPH-d), a marker for nNOS activity, revealed elimination of staining in the illuminated areas following treatment. Whole cell recordings from several neuronal types before, during, and after illumination confirmed the selective damage to non-fast-spiking (FS) interneurons. Treated slices displayed mild disinhibition. The reversal potential of compound synaptic events on pyramidal neurons became more positive, and their decay time constant was elongated, substantiating the removal of an inhibitory conductance. The horizontal decay of local field potentials (LFPs) was significantly reduced at distances of 300-400 μm from the stimulation, but not when inhibition was non-selectively weakened with the GABA(A) blocker picrotoxin. Finally, whereas the depression of LFPs along short trains of 40 Hz stimuli was linearly reduced with distance or initial amplitude in control slices, this ordered relationship was disrupted in DAF-treated slices. These results reveal that NO-producing interneurons in the neocortex convey lateral inhibition to neighboring columns, and shape the spatiotemporal dynamics of the network's activity.

Synthetic Ligands of Cannabinoid Receptors Affect Dauer Formation in the Nematode Caenorhabditis elegans.

PubMed

Reis Rodrigues, Pedro; Kaul, Tiffany K; Ho, Jo-Hao; Lucanic, Mark; Burkewitz, Kristopher; Mair, William B; Held, Jason M; Bohn, Laura M; Gill, Matthew S

2016-06-01

Under adverse environmental conditions the nematode Caenorhabditis elegans can enter an alternate developmental stage called the dauer larva. To identify lipophilic signaling molecules that influence this process, we screened a library of bioactive lipids and found that AM251, an antagonist of the human cannabinoid (CB) receptor, suppresses dauer entry in daf-2 insulin receptor mutants. AM251 acted synergistically with glucose supplementation indicating that the metabolic status of the animal influenced the activity of this compound. Similarly, loss of function mutations in the energy-sensing AMP-activated kinase subunit, aak-2, enhanced the dauer-suppressing effects of AM251, while constitutive activation of aak-2 in neurons was sufficient to inhibit AM251 activity. Chemical epistasis experiments indicated that AM251 acts via G-protein signaling and requires the TGF-β ligand DAF-7, the insulin peptides DAF-28 and INS-6, and a functional ASI neuron to promote reproductive growth. AM251 also required the presence of the SER-5 serotonin receptor, but in vitro experiments suggest that this may not be via a direct interaction. Interestingly, we found that other antagonists of mammalian CB receptors also suppress dauer entry, while the nonselective CB receptor agonist, O-2545, not only inhibited the activity of AM251, but also was able to promote dauer entry when administered alone. Since worms do not have obvious orthologs of CB receptors, the effects of synthetic CBs on neuroendocrine signaling in C. elegans are likely to be mediated via another, as yet unknown, receptor mechanism. However, we cannot exclude the existence of a noncanonical CB receptor in C. elegans. Copyright © 2016 Rodrigues et al.

Synthetic Ligands of Cannabinoid Receptors Affect Dauer Formation in the Nematode Caenorhabditis elegans

PubMed Central

Reis Rodrigues, Pedro; Kaul, Tiffany K.; Ho, Jo-Hao; Lucanic, Mark; Burkewitz, Kristopher; Mair, William B.; Held, Jason M.; Bohn, Laura M.; Gill, Matthew S.

2016-01-01

Under adverse environmental conditions the nematode Caenorhabditis elegans can enter an alternate developmental stage called the dauer larva. To identify lipophilic signaling molecules that influence this process, we screened a library of bioactive lipids and found that AM251, an antagonist of the human cannabinoid (CB) receptor, suppresses dauer entry in daf-2 insulin receptor mutants. AM251 acted synergistically with glucose supplementation indicating that the metabolic status of the animal influenced the activity of this compound. Similarly, loss of function mutations in the energy-sensing AMP-activated kinase subunit, aak-2, enhanced the dauer-suppressing effects of AM251, while constitutive activation of aak-2 in neurons was sufficient to inhibit AM251 activity. Chemical epistasis experiments indicated that AM251 acts via G-protein signaling and requires the TGF-β ligand DAF-7, the insulin peptides DAF-28 and INS-6, and a functional ASI neuron to promote reproductive growth. AM251 also required the presence of the SER-5 serotonin receptor, but in vitro experiments suggest that this may not be via a direct interaction. Interestingly, we found that other antagonists of mammalian CB receptors also suppress dauer entry, while the nonselective CB receptor agonist, O-2545, not only inhibited the activity of AM251, but also was able to promote dauer entry when administered alone. Since worms do not have obvious orthologs of CB receptors, the effects of synthetic CBs on neuroendocrine signaling in C. elegans are likely to be mediated via another, as yet unknown, receptor mechanism. However, we cannot exclude the existence of a noncanonical CB receptor in C. elegans. PMID:27172180

Diterpenes biochemical profile and transcriptional analysis of cytochrome P450s genes in leaves, roots, flowers, and during Coffea arabica L. fruit development.

PubMed

Ivamoto, Suzana T; Sakuray, Leonardo M; Ferreira, Lucia P; Kitzberger, Cíntia S G; Scholz, Maria B S; Pot, David; Leroy, Thierry; Vieira, Luiz G E; Domingues, Douglas S; Pereira, Luiz F P

2017-02-01

Lipids are among the major chemical compounds present in coffee beans, and they affect the flavor and aroma of the coffee beverage. Coffee oil is rich in kaurene diterpene compounds, mainly cafestol (CAF) and kahweol (KAH), which are related to plant defense mechanisms and to nutraceutical and sensorial beverage characteristics. Despite their importance, the final steps of coffee diterpenes biosynthesis remain unknown. To understand the molecular basis of coffee diterpenes biosynthesis, we report the content dynamics of CAF and KAH in several Coffea arabica tissues and the transcriptional analysis of cytochrome P450 genes (P450). We measured CAF and KAH concentrations in leaves, roots, flower buds, flowers and fruit tissues at seven developmental stages (30-240 days after flowering - DAF) using HPLC. Higher CAF levels were detected in flower buds and flowers when compared to fruits. In contrast, KAH concentration increased along fruit development, peaking at 120 DAF. We did not detect CAF or KAH in leaves, and higher amounts of KAH than CAF were detected in roots. Using P450 candidate genes from a coffee EST database, we performed RT-qPCR transcriptional analysis of leaves, flowers and fruits at three developmental stages (90, 120 and 150 DAF). Three P450 genes (CaCYP76C4, CaCYP82C2 and CaCYP74A1) had transcriptional patterns similar to CAF concentration and two P450 genes (CaCYP71A25 and CaCYP701A3) have transcript accumulation similar to KAH concentration. These data warrant further investigation of these P450s as potential candidate genes involved in the final stages of the CAF and KAH biosynthetic pathways. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

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

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

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

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 effectsmore » 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.« less

The Mechanism of Helium-Induced Preconditioning: A Direct Role for Nitric Oxide in Rabbits

PubMed Central

Pagel, Paul S.; Krolikowski, John G.; Pratt, Phillip F.; Shim, Yon Hee; Amour, Julien; Warltier, David C.; Weihrauch, Dorothee

2008-01-01

BACKGROUND Helium produces preconditioning against myocardial infarction by activating prosurvival signaling, but whether nitric oxide (NO) generated by endothelial NO synthase plays a role in this phenomenon is unknown. We tested the hypothesis that NO mediates helium-induced cardioprotection in vivo. METHODS Rabbits (n = 62) instrumented for hemodynamic measurement were subjected to a 30-min left anterior descending coronary artery occlusion and 3 h reperfusion, and received 0.9% saline (control) or three cycles of 70% helium–30% oxygen administered for 5 min interspersed with 5 min of an air–oxygen mixture before left anterior descending coronary artery occlusion in the absence or presence of pretreatment with the nonselective NOS inhibitor N-nitro-l-arginine methyl ester (L-NAME; 10 mg/kg), the selective inducible NOS inhibitor aminoguanidine hydrochloride (AG; 300 mg/kg), or selective neuronal NOS inhibitor 7-nitroindazole (7-NI; 50 mg/kg). In additional rabbits, the fluorescent probe 4,5-diaminofluroscein diacetate (DAF-2DA) and confocal laser microscopy were used to detect NO production in the absence or presence of helium with or without L-NAME pretreatment. RESULTS Helium reduced (P < 0.05) infarct size (24% ± 4% of the left ventricular area at risk; mean ± sd) compared with control (46% ± 3%). L-NAME, AG, and 7-NI did not alter myocardial infarct size when administered alone. L-NAME, but not 7-NI or AG, abolished helium-induced cardioprotection. Helium enhanced DAF-2DA fluorescence compared with control (26 ± 8 vs 15 ± 5 U, respectively). Pretreatment with L-NAME abolished these helium-induced increases in DAF-2DA fluorescence. CONCLUSIONS The results indicate that cardioprotection by helium is mediated by NO that is probably generated by endothelial NOS in vivo. PMID:18713880

The Effects of Fluency Enhancing Conditions on Sensorimotor Control of Speech in Typically Fluent Speakers: An EEG Mu Rhythm Study

PubMed Central

Kittilstved, Tiffani; Reilly, Kevin J.; Harkrider, Ashley W.; Casenhiser, Devin; Thornton, David; Jenson, David E.; Hedinger, Tricia; Bowers, Andrew L.; Saltuklaroglu, Tim

2018-01-01

Objective: To determine whether changes in sensorimotor control resulting from speaking conditions that induce fluency in people who stutter (PWS) can be measured using electroencephalographic (EEG) mu rhythms in neurotypical speakers. Methods: Non-stuttering (NS) adults spoke in one control condition (solo speaking) and four experimental conditions (choral speech, delayed auditory feedback (DAF), prolonged speech and pseudostuttering). Independent component analysis (ICA) was used to identify sensorimotor μ components from EEG recordings. Time-frequency analyses measured μ-alpha (8–13 Hz) and μ-beta (15–25 Hz) event-related synchronization (ERS) and desynchronization (ERD) during each speech condition. Results: 19/24 participants contributed μ components. Relative to the control condition, the choral and DAF conditions elicited increases in μ-alpha ERD in the right hemisphere. In the pseudostuttering condition, increases in μ-beta ERD were observed in the left hemisphere. No differences were present between the prolonged speech and control conditions. Conclusions: Differences observed in the experimental conditions are thought to reflect sensorimotor control changes. Increases in right hemisphere μ-alpha ERD likely reflect increased reliance on auditory information, including auditory feedback, during the choral and DAF conditions. In the left hemisphere, increases in μ-beta ERD during pseudostuttering may have resulted from the different movement characteristics of this task compared with the solo speaking task. Relationships to findings in stuttering are discussed. Significance: Changes in sensorimotor control related feedforward and feedback control in fluency-enhancing speech manipulations can be measured using time-frequency decompositions of EEG μ rhythms in neurotypical speakers. This quiet, non-invasive, and temporally sensitive technique may be applied to learn more about normal sensorimotor control and fluency enhancement in PWS. PMID:29670516

Inheritance of dermatoglyphic asymmetry and diversity traits in twins based on factor: variance decomposition analysis.

PubMed

Karmakar, Bibha; Malkin, Ida; Kobyliansky, Eugene

2013-06-01

Dermatoglyphic asymmetry and diversity traits from a large number of twins (MZ and DZ) were analyzed based on principal factors to evaluate genetic effects and common familial environmental influences on twin data by the use of maximum likelihood-based Variance decomposition analysis. Sample consists of monozygotic (MZ) twins of two sexes (102 male pairs and 138 female pairs) and 120 pairs of dizygotic (DZ) female twins. All asymmetry (DA and FA) and diversity of dermatoglyphic traits were clearly separated into factors. These are perfectly corroborated with the earlier studies in different ethnic populations, which indicate a common biological validity perhaps exists of the underlying component structures of dermatoglyphic characters. Our heritability result in twins clearly showed that DA_F2 is inherited mostly in dominant type (28.0%) and FA_F1 is additive (60.7%), but no significant difference in sexes was observed for these factors. Inheritance is also very prominent in diversity Factor 1, which is exactly corroborated with our previous findings. The present results are similar with the earlier results of finger ridge count diversity in twin data, which suggested that finger ridge count diversity is under genetic control.

Analog-Digital-Wandler

NASA Astrophysics Data System (ADS)

Döring, Peter

Analogsignale in digital codierter Form haben Vorteile (z. B. Speicherung, Übertragung). Ein Beispiel dafür ist die Musik-Film-CD/DVD. In diesem Kapitel werden entsprechende Verfahren vorgestellt. Themen: Grundlagen; Spannungs-Frequenz-Umsetzer: Sägezahn-Verfahren; Dual-Slope-Verfahren; Flash-Umsetzer; Umsetzer nach dem Wägeverfahren. Integrierte Umsetzer.

Lipidomic and proteomic analysis of Caenorhabditis elegans lipid droplets and identification of ACS-4 as a lipid droplet-associated protein

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

Vrablik, Tracy L.; Petyuk, Vladislav A.; Larson, Emily M.

2015-06-27

Lipid droplets are cytoplasmic organelles that store neutral lipids for membrane synthesis and energy reserves. In this study, we characterized the lipid and protein composition of purified C. elegans lipid droplets. These lipid droplets are composed mainly of triacylglycerols, surrounded by a phospholipid monolayer composed primarily of phosphatidylcholine and phosphatidylethanolamine. The fatty acid composition of the triacylglycerols was rich in fatty acid species obtained from the dietary E. coli, including cyclopropane fatty acids and cis-vaccenic acid. Unlike other organisms, C. elegans lipid droplets contain very little cholesterol or cholesterol esters. Comparison of the lipid droplet proteomes of wild type andmore » high-fat daf-2 mutant strains shows a relative decrease of MDT-28 abundance in lipid droplets isolated from daf-2 mutants. Functional analysis of lipid droplet proteins identified in our proteomic studies indicated an enrichment of proteins required for growth and fat homeostasis in C. elegans.« less

Anaerobic Treatment of Palm Oil Mill Effluent in Pilot-Scale Anaerobic EGSB Reactor

PubMed Central

Mahmood, Qaisar; Qiu, Jiang-Ping; Li, Yin-Sheng; Chang, Yoon-Seong; Li, Xu-Dong

2015-01-01

Large volumes of untreated palm oil mill effluent (POME) pose threat to aquatic environment due to the presence of very high organic content. The present investigation involved two pilot-scale anaerobic expanded granular sludge bed (EGSB) reactors, continuously operated for 1 year to treat POME. Setting HRT at 9.8 d, the anaerobic EGSB reactors reduced COD from 71179 mg/L to 12341 mg/L and recycled half of sludge by a dissolved air flotation (DAF). The average effluent COD was 3587 mg/L with the consistent COD removal efficiency of 94.89%. Adding cationic polymer (PAM) dose of 30 mg/L to DAF unit and recycling its half of sludge caused granulation of anaerobic sludge. Bacilli and small coccid bacteria were the dominant microbial species of the reactor. The reactor produced 27.65 m3 of biogas per m3 of POME which was utilized for electricity generation. PMID:26167485

Exposure to the metabolic inhibitor sodium azide induces stress protein expression and thermotolerance in the nematode Caenorhabditis elegans

PubMed Central

Massie, Michelle R.; Lapoczka, Elizabeth M.; Boggs, Kristy D.; Stine, Karen E.; White, Glenn E.

2003-01-01

Historically, sodium azide has been used to anesthetize the nematode Caenorhabditis elegans; however, the mechanism by which it survives this exposure is not understood. In this study, we report that exposure of wild-type C elegans to 10 mM sodium azide for up to 90 minutes confers thermotolerance (defined as significantly increased survival probability [SP] at 37°C) on the animal. In addition, sodium dodecyl sulfate–polyacrylamide gel electrophoresis revealed enhanced Hsp70 expression, whereas Western blot analysis revealed the induction of Hsp16. We also tested the only known C elegans Hsp mutant daf-21 (codes for Hsp90), which constitutively enters the stress-resistant state known as the dauer larvae. Daf-21 mutants also acquire sodium azide–induced thermotolerance, whereas 3 non-Hsp, constitutive dauer-forming mutants exhibited a variable response to azide exposure. We conclude that the ability of C elegans to survive exposure to azide is associated with the induction of at least 2 stress proteins. PMID:12820649

Methylation of the sterol nucleus by STRM-1 regulates dauer larva formation in Caenorhabditis elegans.

PubMed

Hannich, J Thomas; Entchev, Eugeni V; Mende, Fanny; Boytchev, Hristio; Martin, René; Zagoriy, Vyacheslav; Theumer, Gabriele; Riezman, Isabelle; Riezman, Howard; Knölker, Hans-Joachim; Kurzchalia, Teymuras V

2009-06-01

In response to pheromone(s), Caenorhabditis elegans interrupts its reproductive life cycle and enters diapause as a stress-resistant dauer larva. This decision is governed by a complex system of neuronal and hormonal regulation. All the signals converge onto the nuclear hormone receptor DAF-12. A sterol-derived hormone, dafachronic acid (DA), supports reproductive development by binding to DAF-12 and inhibiting its dauer-promoting activity. Here, we identify a methyltransferase, STRM-1, that modulates DA levels and thus dauer formation. By modifying the substrates that are used for the synthesis of DA, STRM-1 can reduce the amount of hormone produced. Loss of STRM-1 function leads to elevated levels of DA and inefficient dauer formation. Sterol methylation was not previously recognized as a mechanism for regulating hormone activity. Moreover, the C-4 sterol nucleus methylation catalyzed by STRM-1 is unique to nematodes and thus could be a target for therapeutic strategies against parasitic nematode infections.

Positive selection of Caenorhabditis elegans mutants with increased stress resistance and longevity.

PubMed Central

Muñoz, Manuel J; Riddle, Donald L

2003-01-01

We developed selective conditions for long-lived mutants of the nematode Caenorhabditis elegans by subjecting the first larval stage (L1) to thermal stress at 30 degrees for 7 days. The surviving larvae developed to fertile adults after the temperature was shifted to 15 degrees. A total of one million F(2) progeny and a half million F(3) progeny of ethyl-methanesulfonate-mutagenized animals were treated in three separate experiments. Among the 81 putative mutants that recovered and matured to the reproductive adult, 63 retested as thermotolerant and 49 (80%) exhibited a >15% increase in mean life span. All the known classes of dauer formation (Daf) mutant that affect longevity were found, including six new alleles of daf-2, and a unique temperature-sensitive, dauer-constitutive allele of age-1. Alleles of dyf-2 and unc-13 were isolated, and mutants of unc-18, a gene that interacts with unc-13, were also found to be long lived. Thirteen additional mutations define at least four new genes. PMID:12586705

Poultry slaughterhouse wastewater treatment plant for high quality effluent.

PubMed

Del Nery, V; Damianovic, M H Z; Moura, R B; Pozzi, E; Pires, E C; Foresti, E

2016-01-01

This paper assesses a wastewater treatment plant (WWTP) regarding the technology used, as well as organic matter and nutrient removal efficiencies aiming to optimize the treatment processes involved and wastewater reclamation. The WWTP consists of a dissolved air flotation (DAF) system, an upflow anaerobic sludge blanket (UASB) reactor, an aerated-facultative pond (AFP) and a chemical-DAF system. The removal efficiencies of chemical oxygen demand (COD) (97.9 ± 1.0%), biochemical oxygen demand (BOD) (98.6 ± 1.0%) and oil and grease (O&G) (91.1 ± 5.2%) at the WWTP, the nitrogen concentration of 17 ± 11 mg N-NH3 and phosphorus concentration of 1.34 ± 0.93 mg PO4(-3)/L in the final effluent indicate that the processes used are suitable to comply with discharge standards in water bodies. Nitrification and denitrification tests conducted using biomass collected at three AFP points indicated that nitrification and denitrification could take place in the pond.

Signal Processing in Cold Atom Interferometry-Based INS

DTIC Science & Technology

2014-03-27

INTERFEROMETRY-BASED INS Kara M. Willis, BS Civilian, DAF Approved: //signed// Meir Pachter, PhD (Chairman) //signed// Maj Marshall Haker , PhD (Member) //signed...matter mentors, Maj Marshall Haker and Dr Kyle Kauffman, for their insights and unwavering encouragement. Kara M. Willis v Table of Contents Page

Insulin/IGF-1 signaling mutants reprogram ER stress response regulators to promote longevity.

PubMed

Henis-Korenblit, Sivan; Zhang, Peichuan; Hansen, Malene; McCormick, Mark; Lee, Seung-Jae; Cary, Michael; Kenyon, Cynthia

2010-05-25

When unfolded proteins accumulate in the endoplasmic reticulum (ER), the unfolded protein response is activated. This ER stress response restores ER homeostasis by coordinating processes that decrease translation, degrade misfolded proteins, and increase the levels of ER-resident chaperones. Ribonuclease inositol-requiring protein-1 (IRE-1), an endoribonuclease that mediates unconventional splicing, and its target, the XBP-1 transcription factor, are key mediators of the unfolded protein response. In this study, we show that in Caenorhabditis elegans insulin/IGF-1 pathway mutants, IRE-1 and XBP-1 promote lifespan extension and enhance resistance to ER stress. We show that these effects are not achieved simply by increasing the level of spliced xbp-1 mRNA and expression of XBP-1's normal target genes. Instead, in insulin/IGF-1 pathway mutants, XBP-1 collaborates with DAF-16, a FOXO-transcription factor that is activated in these mutants, to enhance ER stress resistance and to activate new genes that promote longevity.

Lifespan-extending effects of royal jelly and its related substances on the nematode Caenorhabditis elegans.

PubMed

Honda, Yoko; Fujita, Yasunori; Maruyama, Hiroe; Araki, Yoko; Ichihara, Kenji; Sato, Akira; Kojima, Toshio; Tanaka, Masashi; Nozawa, Yoshinori; Ito, Masafumi; Honda, Shuji

2011-01-01

One of the most important challenges in the study of aging is to discover compounds with longevity-promoting activities and to unravel their underlying mechanisms. Royal jelly (RJ) has been reported to possess diverse beneficial properties. Furthermore, protease-treated RJ (pRJ) has additional pharmacological activities. Exactly how RJ and pRJ exert these effects and which of their components are responsible for these effects are largely unknown. The evolutionarily conserved mechanisms that control longevity have been indicated. The purpose of the present study was to determine whether RJ and its related substances exert a lifespan-extending function in the nematode Caenorhabditis elegans and to gain insights into the active agents in RJ and their mechanism of action. We found that both RJ and pRJ extended the lifespan of C. elegans. The lifespan-extending activity of pRJ was enhanced by Octadecyl-silica column chromatography (pRJ-Fraction 5). pRJ-Fr.5 increased the animals' lifespan in part by acting through the FOXO transcription factor DAF-16, the activation of which is known to promote longevity in C. elegans by reducing insulin/IGF-1 signaling (IIS). pRJ-Fr.5 reduced the expression of ins-9, one of the insulin-like peptide genes. Moreover, pRJ-Fr.5 and reduced IIS shared some common features in terms of their effects on gene expression, such as the up-regulation of dod-3 and the down-regulation of dod-19, dao-4 and fkb-4. 10-Hydroxy-2-decenoic acid (10-HDA), which was present at high concentrations in pRJ-Fr.5, increased lifespan independently of DAF-16 activity. These results demonstrate that RJ and its related substances extend lifespan in C. elegans, suggesting that RJ may contain longevity-promoting factors. Further analysis and characterization of the lifespan-extending agents in RJ and pRJ may broaden our understanding of the gene network involved in longevity regulation in diverse species and may lead to the development of nutraceutical interventions in the aging process.

Integrated Strategic Planning and Analysis Network Increment 4 (ISPAN Inc 4)

DTIC Science & Technology

2016-03-01

Defense Acquisition Executive DoD - Department of Defense DoDAF - DoD Architecture Framework FD - Full Deployment FDD - Full Deployment Decision FY...Inc 4 will achieve FDD completion criteria when: 1) the system meets all the KPP thresholds as verified through an Initial Operational Test and

Integrated Strategic Planning and Analysis Network Increment 5 (ISPAN Inc 5)

DTIC Science & Technology

2016-03-01

Defense Acquisition Executive DoD - Department of Defense DoDAF - DoD Architecture Framework FD - Full Deployment FDD - Full Deployment Decision...achieve FDD in August 2018. ISPAN Inc 5 is envisioned as a follow-on to ISPAN Inc 4 in order to respond to USSTRATCOM requirements for improved

KiloPower Program

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

McClure, Patrick Ray

2016-08-04

These are the slides for a phone interview with Aerospace America magazine of the AIAA. It goes over the KiloPower Program at Los Alamos National Laboratory (LANL), and covers the following: 1 kWe Kilopower, 10 kWe Kilopower, Kilopower Reactor Using Stirling Technology (KRUSTY) Integration Test (DAF), Reactor Configuration, and Platen Positions.

Net-centric ACT-R-Based Cognitive Architecture with DEVS Unified Process

DTIC Science & Technology

2011-04-01

effort has been spent in analyzing various forms of requirement specifications, viz, state-based, Natural Language based, UML-based, Rule- based, BPMN ...requirement specifications in one of the chosen formats such as BPMN , DoDAF, Natural Language Processing (NLP) based, UML- based, DSL or simply

Genes down-regulated in spaceflight are involved in the control of longevity in Caenorhabditis elegans.

PubMed

Honda, Yoko; Higashibata, Akira; Matsunaga, Yohei; Yonezawa, Yukiko; Kawano, Tsuyoshi; Higashitani, Atsushi; Kuriyama, Kana; Shimazu, Toru; Tanaka, Masashi; Szewczyk, Nathaniel J; Ishioka, Noriaki; Honda, Shuji

2012-01-01

How microgravitational space environments affect aging is not well understood. We observed that, in Caenorhabditis elegans, spaceflight suppressed the formation of transgenically expressed polyglutamine aggregates, which normally accumulate with increasing age. Moreover, the inactivation of each of seven genes that were down-regulated in space extended lifespan on the ground. These genes encode proteins that are likely related to neuronal or endocrine signaling: acetylcholine receptor, acetylcholine transporter, choline acetyltransferase, rhodopsin-like receptor, glutamate-gated chloride channel, shaker family of potassium channel, and insulin-like peptide. Most of them mediated lifespan control through the key longevity-regulating transcription factors DAF-16 or SKN-1 or through dietary-restriction signaling, singly or in combination. These results suggest that aging in C. elegans is slowed through neuronal and endocrine response to space environmental cues.

Genes down-regulated in spaceflight are involved in the control of longevity in Caenorhabditis elegans

PubMed Central

Honda, Yoko; Higashibata, Akira; Matsunaga, Yohei; Yonezawa, Yukiko; Kawano, Tsuyoshi; Higashitani, Atsushi; Kuriyama, Kana; Shimazu, Toru; Tanaka, Masashi; Szewczyk, Nathaniel J.; Ishioka, Noriaki; Honda, Shuji

2012-01-01

How microgravitational space environments affect aging is not well understood. We observed that, in Caenorhabditis elegans, spaceflight suppressed the formation of transgenically expressed polyglutamine aggregates, which normally accumulate with increasing age. Moreover, the inactivation of each of seven genes that were down-regulated in space extended lifespan on the ground. These genes encode proteins that are likely related to neuronal or endocrine signaling: acetylcholine receptor, acetylcholine transporter, choline acetyltransferase, rhodopsin-like receptor, glutamate-gated chloride channel, shaker family of potassium channel, and insulin-like peptide. Most of them mediated lifespan control through the key longevity-regulating transcription factors DAF-16 or SKN-1 or through dietary-restriction signaling, singly or in combination. These results suggest that aging in C. elegans is slowed through neuronal and endocrine response to space environmental cues. PMID:22768380

Food-derived sensory cues modulate longevity via distinct neuroendocrine insulin-like peptides

PubMed Central

Artan, Murat; Jeong, Dae-Eun; Lee, Dongyeop; Kim, Young-Il; Son, Heehwa G.; Husain, Zahabiya; Kim, Jinmahn; Altintas, Ozlem; Kim, Kyuhyung; Alcedo, Joy; Lee, Seung-Jae V.

2016-01-01

Environmental fluctuations influence organismal aging by affecting various regulatory systems. One such system involves sensory neurons, which affect life span in many species. However, how sensory neurons coordinate organismal aging in response to changes in environmental signals remains elusive. Here, we found that a subset of sensory neurons shortens Caenorhabditis elegans’ life span by differentially regulating the expression of a specific insulin-like peptide (ILP), INS-6. Notably, treatment with food-derived cues or optogenetic activation of sensory neurons significantly increases ins-6 expression and decreases life span. INS-6 in turn relays the longevity signals to nonneuronal tissues by decreasing the activity of the transcription factor DAF-16/FOXO. Together, our study delineates a mechanism through which environmental sensory cues regulate aging rates by modulating the activities of specific sensory neurons and ILPs. PMID:27125673

Enterovirus strain and type-specific differences in growth kinetics and virus-induced cell destruction in human pancreatic duct epithelial HPDE cells.

PubMed

Smura, Teemu; Natri, Olli; Ylipaasto, Petri; Hellman, Marika; Al-Hello, Haider; Piemonti, Lorenzo; Roivainen, Merja

2015-12-02

Enterovirus infections have been suspected to be involved in the development of type 1 diabetes. However, the pathogenetic mechanism of enterovirus-induced type 1 diabetes is not known. Pancreatic ductal cells are closely associated with pancreatic islets. Therefore, enterovirus infections in ductal cells may also affect beta-cells and be involved in the induction of type 1 diabetes. The aim of this study was to assess the ability of different enterovirus strains to infect, replicate and produce cytopathic effect in human pancreatic ductal cells. Furthermore, the viral factors that affect these capabilities were studied. The pancreatic ductal cells were highly susceptible to enterovirus infections. Both viral growth and cytolysis were detected for several enterovirus serotypes. However, the viral growth and capability to induce cytopathic effect (cpe) did not correlate completely. Some of the virus strains replicated in ductal cells without apparent cpe. Furthermore, there were strain-specific differences in the growth kinetics and the ability to cause cpe within some serotypes. Viral adaptation experiments were carried out to study the potential genetic determinants behind these phenotypic differences. The blind-passage of non-lytic CV-B6-Schmitt strain in HPDE-cells resulted in lytic phenotype and increased progeny production. This was associated with the substitution of a single amino acid (K257E) in the virus capsid protein VP1 and the viral ability to use decay accelerating factor (DAF) as a receptor. This study demonstrates considerable plasticity in the cell tropism, receptor usage and cytolytic properties of enteroviruses and underlines the strong effect of single or few amino acid substitutions in cell tropism and lytic capabilities of a given enterovirus. Since ductal cells are anatomically close to pancreatic islets, the capability of enteroviruses to infect and destroy pancreatic ductal cells may also implicate in respect to enterovirus induced type 1 diabetes. In addition, the capability for rapid adaptation to different cell types suggests that, on occasion, enterovirus strains with different pathogenetic properties may arise from less pathogenic ancestors. Copyright © 2015 Elsevier B.V. All rights reserved.

Towards Greater Individualization and Process-Oriented Learning through Electronic Self-Access: Project "e-daf"

ERIC Educational Resources Information Center

Chan, Wai Meng; Kim, Dong-Ha

2004-01-01

Research in cognitive psychology and second language learning has underlined the significance of learners' cognitive processes and individual preferences in language learning. Helping learners to be aware of these processes and preferences has in fact become an important methodological principle of language teaching. Advances in information and…

Consolidated Afloat Networks and Enterprise Services (CANES)

DTIC Science & Technology

2016-03-01

Executive DoD - Department of Defense DoDAF - DoD Architecture Framework FD - Full Deployment FDD - Full Deployment Decision FY - Fiscal Year IA...Deployment Decision Jun 2015 Oct 2015 Full Deployment1 Sep 2024 Sep 2023 Memo 1/ Per the FDD ADM approved by USD(AT&L) on October 13, 2015, the FD date was

Deliberate and Crisis Action Planning and Execution Segments Increment 2A (DCAPES Inc 2A)

DTIC Science & Technology

2016-03-01

Document DAE - Defense Acquisition Executive DoD - Department of Defense DoDAF - DoD Architecture Framework FD - Full Deployment FDD - Full...Jun 2009 DT/OT Completion Jan 2015 Jan 2015 FDD Aug 2015 Oct 2015 FD TBD Oct 2015 Memo DCAPES is a National Security System. Acronyms and

Historical Lessons of Air Force Communications

DTIC Science & Technology

2010-12-01

AU/ACSC/ CUSTINE /AY10 AIR COMMAND AND STAFF COLLEGE AIR UNIVERSITY HISTORICAL LESSONS OF AIR FORCE COMMUNICATIONS...by Jay D. Custine , Civ, DAF A Research Report Submitted to the Faculty In Partial Fulfillment of the Graduation...Requirements Advisor: Lt Col Paul E. Griffith Maxwell Air Force Base, Alabama December 2010 AU/ACSC/ CUSTINE /AY10 ii

The Role of Nanobubbles in the Precipitation and Recovery of Organic-Phosphine-Containing Beneficiation Wastewater.

PubMed

Xiao, Wei; Ke, Shuo; Quan, Nannan; Zhou, Limin; Wang, Jun; Zhang, Lijuan; Dong, Yaming; Qin, Wenqing; Qiu, Guanzhou; Hu, Jun

2018-05-29

Dissolved air flotation (DAF) is broadly applied in wastewater treatment, especially for the recovery of organic pollution with low concentration. However, the mechanism of interaction between nanoscale gas bubbles and nanoparticles in the process of DAF remains unclear. Here, we investigated the role of nanobubbles in the precipitation of styryl phosphoric acid (SPA)-Pb particles and recovering organic phosphine containined in beneficiation wastewater by UV-vis (ultraviolet-visible) spectra, microflotation tests, nanoparticle tracking analysis, dynamic light scattering, and atomic force microscopy measurements. As suggested from the results, nanobubbles can inhibit the crystallization of SPA-Pb precipitation, which makes the sediment flotation recovery below 20%. After the precipitation crystallization is completed, nanobubbles can flocculate precipitated particles, which can promote the flotation recovery of precipitated particles to 90%. On the basis of the results, we proposed a model to explain the different roles of nanobubbles in the process of precipitation and flotation of SPA-Pb particles. This study will be helpful to understand the interaction between nanobubbles and nanoparticles in the application of flotation.

Risk Assessment Update: Russian Segment

NASA Technical Reports Server (NTRS)

Christiansen, Eric; Lear, Dana; Hyde, James; Bjorkman, Michael; Hoffman, Kevin

2012-01-01

BUMPER-II version 1.95j source code was provided to RSC-E- and Khrunichev at January 2012 MMOD TIM in Moscow. MEMCxP and ORDEM 3.0 environments implemented as external data files. NASA provided a sample ORDEM 3.0 g."key" & "daf" environment file set for demonstration and benchmarking BUMPER -II v1.95j installation at the Jan-12 TIM. ORDEM 3.0 has been completed and is currently in beta testing. NASA will provide a preliminary set of ORDEM 3.0 ".key" & ".daf" environment files for the years 2012 through 2028. Bumper output files produced using the new ORDEM 3.0 data files are intended for internal use only, not for requirements verification. Output files will contain these words ORDEM FILE DESCRIPTION = PRELIMINARY VERSION: not for production. The projectile density term in many BUMPER-II ballistic limit equations will need to be updated. Cube demo scripts and output files delivered at the Jan-12 TIM have been updated for the new ORDEM 3.0 data files. Risk assessment results based on ORDEM 3.0 and MEM will be presented for the Russian Segment (RS) of ISS.

Criticality Safety Evaluation for the TACS at DAF

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

Percher, C. M.; Heinrichs, D. P.

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 utilizemore » 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.« less

H3K4 demethylase activities repress proliferative and postmitotic aging

PubMed Central

Alvares, Stacy M; Mayberry, Gaea A; Joyner, Ebony Y; Lakowski, Bernard; Ahmed, Shawn

2014-01-01

Homeostasis of postmitotic and proliferating cells is maintained by pathways that repress stress. We found that the Caenorhabditis elegans histone 3 lysine 4 (H3K4) demethylases RBR-2 and SPR-5 promoted postmitotic longevity of stress-resistant daf-2 adults, altered pools of methylated H3K4, and promoted silencing of some daf-2 target genes. In addition, RBR-2 and SPR-5 were required for germ cell immortality at a high temperature. Transgenerational proliferative aging was enhanced for spr-5; rbr-2 double mutants, suggesting that these histone demethylases may function sequentially to promote germ cell immortality by targeting distinct H3K4 methyl marks. RBR-2 did not play a comparable role in the maintenance of quiescent germ cells in dauer larvae, implying that it represses stress that occurs as a consequence of germ cell proliferation, rather than stress that accumulates in nondividing cells. We propose that H3K4 demethylase activities promote the maintenance of chromatin states during stressful growth conditions, thereby repressing postmitotic aging of somatic cells as well as proliferative aging of germ cells. PMID:24134677

RNA-Sequencing Reveals Biological Networks during Table Grapevine (‘Fujiminori’) Fruit Development

PubMed Central

Shangguan, Lingfei; Mu, Qian; Fang, Xiang; Zhang, Kekun; Jia, Haifeng; Li, Xiaoying; Bao, Yiqun; Fang, Jinggui

2017-01-01

Grapevine berry development is a complex and genetically controlled process, with many morphological, biochemical and physiological changes occurring during the maturation process. Research carried out on grapevine berry development has been mainly concerned with wine grape, while barely focusing on table grape. ‘Fujiminori’ is an important table grapevine cultivar, which is cultivated in most provinces of China. In order to uncover the dynamic networks involved in anthocyanin biosynthesis, cell wall development, lipid metabolism and starch-sugar metabolism in ‘Fujiminori’ fruit, we employed RNA-sequencing (RNA-seq) and analyzed the whole transcriptome of grape berry during development at the expanding period (40 days after full bloom, 40DAF), véraison period (65DAF), and mature period (90DAF). The sequencing depth in each sample was greater than 12×, and the expression level of nearly half of the expressed genes were greater than 1. Moreover, greater than 64% of the clean reads were aligned to the Vitis vinifera reference genome, and 5,620, 3,381, and 5,196 differentially expressed genes (DEGs) were identified between different fruit stages, respectively. Results of the analysis of DEGs showed that the most significant changes in various processes occurred from the expanding stage to the véraison stage. The expression patterns of F3’H and F3’5’H were crucial in determining red or blue color of the fruit skin. The dynamic networks of cell wall development, lipid metabolism and starch-sugar metabolism were also constructed. A total of 4,934 SSR loci were also identified from 4,337 grapevine genes, which may be helpful for the development of phylogenetic analysis in grapevine and other fruit trees. Our work provides the foundation for developmental research of grapevine fruit as well as other non-climacteric fruits. PMID:28118385

Performance evaluation of a granular activated carbon-sequencing batch biofilm reactor pilot plant system used in treating real wastewater from recycled paper industry.

PubMed

Muhamad, Mohd Hafizuddin; Sheikh Abdullah, Siti Rozaimah; Mohamad, Abu Bakar; Rahman, Rakmi Abdul; Kadhum, Abdul Amir Hasan

2012-01-01

A pilot scale granular activated carbon-sequencing batch biofilm reactor with a capacity of 2.2 m3 was operated for over three months to evaluate its performance treating real recycled paper industry wastewater under different operational conditions. In this study, dissolved air floatation (DAF) and clarifier effluents were used as influent sources of the pilot plant. During the course of the study, the reactor was able to biodegrade the contaminants in the incoming recycled paper mill wastewater in terms of chemical oxygen demand (COD), adsorbable organic halides (AOX; specifically 2,4-dichlorophenol (2,4-DCP)) and ammoniacal nitrogen (NH3-N) removal efficiencies at varying hydraulic retention times (HRTs) of 1-3 days, aeration rates (ARs) of 2.1-3.4 m3/min and influent feed concentration of 40-950 mg COD/l. Percentages of COD, 2,4-DCP and NH3-N removals increased with increasing HRT, resulting in more than 90% COD, 2,4-DCP and NH3-N removals at HRT values above two days. Degradation of COD, 2,4-DCP and NH3-N were seriously affected by variation of ARs, which resulted in significant decrease of COD, 2,4-DCP and NH3-N removals by decreasing ARs from 3.4 m3/min to 2.1 m3/min, varying in the ranges of 24-80%, 6-96% and 5-42%, respectively. In comparison to the clarifier effluent, the treatment performance of DAF effluent, containing high COD concentration, resulted in a higher COD removal of 82%. The use of diluted DAF effluent did not improve significantly the COD removal. Higher NH3-N removal efficiency of almost 100% was observed during operation after maintenance shutdown compared to normal operation, even at the same HRT of one day due to the higher dissolved oxygen concentrations (1-7 mg/l), while no significant difference in COD removal efficiency was observed.

Application of flow cytometry with a fluorescent dye to measurement of intracellular nitric oxide in plant cells.

PubMed

Kępczyński, Jan; Cembrowska-Lech, Danuta

2018-04-27

A simple and rapid method involving flow cytometry and NO-specific probe (DAF-FM DA) proved useful for detection and determination of intracellular NO production in Medicago truncatula suspension cells and leaves as well as in cells of Avena fatua, Amaranthus retroflexus embryos and leaves. The measurement of nitric oxide (NO) in plant material is important for examining the regulatory roles of endogenous NO in various physiological processes. The possibility of detecting and determining intracellular NO production by flow cytometry (FCM) with 4-amino-5-methylamino-2',7'-difluorofluorescein (DAF-FM DA), an NO-specific probe in Medicago truncatula cells in suspension and leaves as well as in cells of embryos and leaves of Avena fatua L. or Amaranthus retroflexus L. was explored. To detect and measure NO production by cell suspension or embryos and leaves, the recommended DAF-FM DA concentration is 5 or 10 µM, respectively, applied for 30 min. Exogenous NO increased the intensity of the fluorescent signal in embryos and leaves of both plants, while carboxy-PTIO (cPTIO), an NO scavenger, decreased it. Thus, these results demonstrate that NO can be detected and an increase and a decrease of its intracellular level can be estimated. Wounding was observed to increase the fluorescence signal, indicating an increase in the intracellular NO level. In addition, the levels of exogenous and endogenous ascorbic acid were demonstrated to have no effect on the NO-related fluorescence signal, indicating the signal's specificity only in relation with NO. The applicability of the proposed method for detection and determination of NO was confirmed (1) by in situ NO imaging in cell suspensions and (2) by determining the NO concentration in embryos and leaves using the Griess reagent. In view of the data obtained, FCM is recommended as a rapid and simple method with which to detect and determine intracellular NO production in plant cells.

Comparing the drawings of children with attention deficit hyperactivity disorder with normal children.

PubMed

Haghighi, Mahnaz; Khaterizadeh, Maedeh; Chalbianloo, Gholamreza; Toobaei, Sholeh; Ghanizadeh, Ahmad

2014-10-01

Attention deficit hyperactivity disorder (ADHD) is the most common behavioral problem during childhood and in school-aged children. Various projection drawings have been designed for assessing children's personality and psychological disorders including the tests of draw a person (DAP) and draw a family (DAF). We aimed to compare the differences between typically developing children and children with ADHD using these tests. In this case-control study, all the 9-10 year-old boy students studying at the third and fourth grades were enrolled from schools in the 2nd educational district of Shiraz, south of Iran. Eighty students were then selected and enrolled into the ADHD group and the control group. The Diagnostic and Statistical Manual of Mental Disorders, 4th edition- text Revised (DSM-IV-TR), and the Child Symptoms Inventory were used to diagnose the children with ADHD. We evaluated and analyzed impulsiveness, non-impulsiveness, emotional problems and incompatibility indices in the DAP and DAF tests in each group. A significant difference was found in the indices of incompatibility and emotional problems, impulsiveness, non-impulsiveness and DAF between typically developing children and those with ADHD. The mean (±SD) total scores of the above mentioned indices in the ADHD group were 19.79(±2.94), 12.31(±1.84), 5.26(±2.29) and 5.89(±2.13), respectively (P<0.001). The corresponding figures for these indices in the normal group were 12.11(±4.74), 5.63(±2), 10.36± (2.33) and 2.88(±2.13), respectively (P<0.001). Significant differences were obtained between the control group and children with ADHD using these two drawing tests. The rate of impulsivity and emotional problems indices in drawings of children with ADHD was markedly more common than those of the typically developing children. This suggests the need for further assessment to screen ADHD.

Performation Metrics Development Analysis for Information and Communications Technology Outsourcing: A Case Study

ERIC Educational Resources Information Center

Travis, James L., III

2014-01-01

This study investigated how and to what extent the development and use of the OV-5a operational architecture decomposition tree (OADT) from the Department of Defense (DoD) Architecture Framework (DoDAF) affects requirements analysis with respect to complete performance metrics for performance-based services acquisition of ICT under rigid…

An Experimental Investigation of the Effect of Altered Auditory Feedback on the Conversational Speech of Adults Who Stutter

ERIC Educational Resources Information Center

Lincoln, Michelle; Packman, Ann; Onslow, Mark; Jones, Mark

2010-01-01

Purpose: To investigate the impact on percentage of syllables stuttered of various durations of delayed auditory feedback (DAF), levels of frequency-altered feedback (FAF), and masking auditory feedback (MAF) during conversational speech. Method: Eleven adults who stuttered produced 10-min conversational speech samples during a control condition…

Development and Psychometric Evaluation of the Index of Dental Anxiety and Fear (IDAF-4C[superscript +])

ERIC Educational Resources Information Center

Armfield, Jason M.

2010-01-01

The measurement of dental fear is important due to its high prevalence and appreciable individual, clinical, and public health consequences. However, existing measures of dental anxiety and fear (DAF) have theoretical or practical limitations. This study describes the development and subsequent assessment of the reliability and validity of test…

Integrated Personnel and Pay System-Army Increment 1 (IPPS-A Inc 1)

DTIC Science & Technology

2016-03-01

Acquisition Executive DoD - Department of Defense DoDAF - DoD Architecture Framework FD - Full Deployment FDD - Full Deployment Decision FY...2013 Feb 2014 Increment I FDD Apr 2013 Apr 2014 Full Deployment1 Jan 2015 Jul 2015 Memo Per 10 U.S.C. Chapter 144A, the MS C Decision exceeded the

Global Combat Support System - Joint Increment 8 (GCSS-J Inc 8)

DTIC Science & Technology

2016-03-01

Acquisition Executive DoD - Department of Defense DoDAF - DoD Architecture Framework FD - Full Deployment FDD - Full Deployment Decision FY - Fiscal...Estimate (Or Actual) Milestone B1 Mar 2014 Mar 2014 Milestone C1 Mar 2014 Mar 2014 Increment 8 FDD Dec 2018 Dec 2018 Increment 8 FD TBD TBD Memo 1

The Revised Direct Assessment of Functional Status for Independent Older Adults

ERIC Educational Resources Information Center

McDougall, Graham J.; Becker, Heather; Vaughan, Phillip W.; Acee, Taylor W.; Delville, Carol L.

2010-01-01

Purpose: The original version of the Direct Assessment of Functional Status (DAFS), a measure of instrumental activities of daily living (IADLs), was found to have a ceiling effect in older adults living independently in the community. This suggested that the tasks measured, although relevant, do not require full use of this population's…

Evidence-based efficacy of adaptogens in fatigue, and molecular mechanisms related to their stress-protective activity.

PubMed

Panossian, Alexander; Wikman, Georg

2009-09-01

The aim of this review article is to assess the level of scientific evidence presented by clinical trials of adaptogens in fatigue, and to provide a rationale at the molecular level for verified effects. Strong scientific evidence is available for Rhodiola rosea SHR-5 extract, which improved attention, cognitive function and mental performance in fatigue and in chronic fatigue syndrome. Good scientific evidence has been documented in trails in which Schisandra chinensis and Eleutherococcus senticosus increased endurance and mental performance in patients with mild fatigue and weakness. Based on their efficacy in clinical studies, adaptogens can be defined as a pharmacological group of herbal preparations that increase tolerance to mental exhaustion and enhance attention and mental endurance in situations of decreased performance. The beneficial stress-protective effect of adaptogens is related to regulation of homeostasis via several mechanisms of action associated with the hypothalamic-pituitary-adrenal axis and the control of key mediators of stress response such as molecular chaperons (e.g. Hsp70), stress-activated c-Jun N-terminal protein kinase (JNK1), Forkhead Box O transcription factor DAF-16, cortisol and nitric oxide (NO). The key point of action of phytoadaptogens appears to be their up-regulating and stress-mimetic effects on the "stress-sensor" protein Hsp70, which plays an important role in cell survival and apoptosis. Hsp70 inhibits the expression of NO synthase II gene and interacts with glucocorticoid receptors directly and via the JNK pathway, thus affecting the levels of circulating cortisol and NO. Prevention of stress-induced increase in NO, and the associated decrease in ATP production, results in increased performance and endurance. Adaptogen-induced up-regulation of Hsp70 triggers stress-induced JNK-1 and DAF-16-mediated pathways regulating the resistance to stress and resulting in enhanced mental and physical performance and, possibly, increased longevity.

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

PubMed

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 suggestion in the data that accelerated students are more socially competent than non-accelerated students. The findings in this study can reassure those parents and teachers who worry about the social-emotional consequences of acceleration in school: If a student is gifted, acceleration seems to be a sound and, in many cases, appropriate measure in gifted education. ©2011 The British Psychological Society.

Reduce oil and grease content in wastewater

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

Capps, R.W.; Matelli, G.N.; Bradford, M.L.

Poor water quality is often blamed on biological oxidation unit malfunction. However, poorly treated water entering the bio-unit is more often the problem. At the microscopic level, oil/water-separation dynamics are influenced by pH, fluid velocity, temperature, and unit volumes. Oily water's physical and chemical properties affect pretreatment systems such as API separators, corrugated plate interception (CPI) separators, air flotation and equalization systems. A better understanding of pretreatment systems' limits and efficiencies can improve wastewater quality before it upsets the biological oxidation (BIOX). Oil contamination in refinery wastewater originates from desalting, steam stripping, product treating, tank drains, sample drains and equipmentmore » washdown. The largest volumetric contributors are cooling tower blowdowns and contaminated stormwater. The paper describes the BIOX process; oil/water separation; oil/water emulsions and colloidal solutions; air flotation; surfactants; DAF (dissolved air flotation) process; IAF (induced air flotation) process; equalization; load factors; salts; and system design.« less

An Anthocyanin-Rich Extract of Acai (Euterpe precatoria Mart.) Increases Stress Resistance and Retards Aging-Related Markers in Caenorhabditis elegans.

PubMed

Peixoto, Herbenya; Roxo, Mariana; Krstin, Sonja; Röhrig, Teresa; Richling, Elke; Wink, Michael

2016-02-17

Acai fruits (Euterpe precatoria) are rich in antioxidant anthocyanins. Acai consumption is believed to have many health benefits; however, relevant detailed scientific investigations are limited. The current study aimed to investigate an anthocyanin-rich extract from E. precatoria fruits (AE) with regard to its antioxidant and antiaging properties using the model organism Caenorhabditis elegans. AE can protect the worms against oxidative stress and can ameliorate accumulation of reactive oxygen species in vivo. The expression of stress-response genes, such as sod-3::GFP, was upregulated while hsp-16::GFP was down-regulated after AE treatment. Studies with DAF-16/FOXO mutants indicated that some of the antioxidant effects are mediated by this transcription factor. AE can modulate the development of age-related markers, such as pharyngeal pumping. Despite the apparent antioxidant activity, no lifespan-prolonging effect was observed.

Structural and Functional Recovery of Sensory Cilia in C. elegans IFT Mutants upon Aging.

PubMed

Cornils, Astrid; Maurya, Ashish K; Tereshko, Lauren; Kennedy, Julie; Brear, Andrea G; Prahlad, Veena; Blacque, Oliver E; Sengupta, Piali

2016-12-01

The majority of cilia are formed and maintained by the highly conserved process of intraflagellar transport (IFT). Mutations in IFT genes lead to ciliary structural defects and systemic disorders termed ciliopathies. Here we show that the severely truncated sensory cilia of hypomorphic IFT mutants in C. elegans transiently elongate during a discrete period of adult aging leading to markedly improved sensory behaviors. Age-dependent restoration of cilia morphology occurs in structurally diverse cilia types and requires IFT. We demonstrate that while DAF-16/FOXO is dispensable, the age-dependent suppression of cilia phenotypes in IFT mutants requires cell-autonomous functions of the HSF1 heat shock factor and the Hsp90 chaperone. Our results describe an unexpected role of early aging and protein quality control mechanisms in suppressing ciliary phenotypes of IFT mutants, and suggest possible strategies for targeting subsets of ciliopathies.

Structural and Functional Recovery of Sensory Cilia in C. elegans IFT Mutants upon Aging

PubMed Central

Kennedy, Julie; Brear, Andrea G.; Prahlad, Veena; Blacque, Oliver E.; Sengupta, Piali

2016-01-01

The majority of cilia are formed and maintained by the highly conserved process of intraflagellar transport (IFT). Mutations in IFT genes lead to ciliary structural defects and systemic disorders termed ciliopathies. Here we show that the severely truncated sensory cilia of hypomorphic IFT mutants in C. elegans transiently elongate during a discrete period of adult aging leading to markedly improved sensory behaviors. Age-dependent restoration of cilia morphology occurs in structurally diverse cilia types and requires IFT. We demonstrate that while DAF-16/FOXO is dispensable, the age-dependent suppression of cilia phenotypes in IFT mutants requires cell-autonomous functions of the HSF1 heat shock factor and the Hsp90 chaperone. Our results describe an unexpected role of early aging and protein quality control mechanisms in suppressing ciliary phenotypes of IFT mutants, and suggest possible strategies for targeting subsets of ciliopathies. PMID:27906968

Food-derived sensory cues modulate longevity via distinct neuroendocrine insulin-like peptides.

PubMed

Artan, Murat; Jeong, Dae-Eun; Lee, Dongyeop; Kim, Young-Il; Son, Heehwa G; Husain, Zahabiya; Kim, Jinmahn; Altintas, Ozlem; Kim, Kyuhyung; Alcedo, Joy; Lee, Seung-Jae V

2016-05-01

Environmental fluctuations influence organismal aging by affecting various regulatory systems. One such system involves sensory neurons, which affect life span in many species. However, how sensory neurons coordinate organismal aging in response to changes in environmental signals remains elusive. Here, we found that a subset of sensory neurons shortens Caenorhabditis elegans' life span by differentially regulating the expression of a specific insulin-like peptide (ILP), INS-6. Notably, treatment with food-derived cues or optogenetic activation of sensory neurons significantly increases ins-6 expression and decreases life span. INS-6 in turn relays the longevity signals to nonneuronal tissues by decreasing the activity of the transcription factor DAF-16/FOXO. Together, our study delineates a mechanism through which environmental sensory cues regulate aging rates by modulating the activities of specific sensory neurons and ILPs. © 2016 Artan et al.; Published by Cold Spring Harbor Laboratory Press.

Perspectives on anaerobic treatment in developing countries.

PubMed

Foresti, E

2001-01-01

Developing countries occupy regions where the climate is warm most of the time. Even in sub-tropical areas, low temperatures do not persist for long periods. This is the main factor that makes the use of anaerobic technology applicable and less expensive, even for the treatment of low-strength industrial wastewaters and domestic sewage. Based mainly on papers presented at the "VI Latin-American Workshop and Seminar on Anaerobic Digestion" held in Recife, Brazil, in November 2000, this text approaches the perspectives of anaerobic treatment of wastewaters in developing countries. Emphasis is given to domestic sewage treatment and to the use of compact systems in which sequential batch reactors (SBR) or dissolvedair flotation (DAF) systems are applied for the post-treatment of anaerobic reactor effluents. Experiments on bench- and pilot-plants have indicated that these systems can achieve high performance in removing organic matter and nutrients during the treatment of domestic sewage at ambient temperatures.

The cell non-autonomous function of ATG-18 is essential for neuroendocrine regulation of Caenorhabditis elegans lifespan

PubMed Central

Minnerly, Justin; Zhang, Jiuli; Parker, Thomas

2017-01-01

Dietary restriction (DR) and reduced insulin growth factor (IGF) signaling extend lifespan in Caenorhabditis elegans and other eukaryotic organisms. Autophagy, an evolutionarily conserved lysosomal degradation pathway, has emerged as a central pathway regulated by various longevity signals including DR and IGF signaling in promoting longevity in a variety of eukaryotic organisms. However, the mechanism remains unclear. Here we show that the autophagy protein ATG-18 acts cell non-autonomously in neuronal and intestinal tissues to maintain C. elegans wildtype lifespan and to respond to DR and IGF-mediated longevity signaling. Moreover, ATG-18 activity in chemosensory neurons that are involved in food detection sufficiently mediates the effect of these longevity pathways. Additionally, ATG-18-mediated cell non-autonomous signaling depends on the release of neurotransmitters and neuropeptides. Interestingly, our data suggest that neuronal and intestinal ATG-18 acts in parallel and converges on unidentified neurons that secrete neuropeptides to regulate C. elegans lifespan through the transcription factor DAF-16/FOXO in response to reduced IGF signaling. PMID:28557996

Preoperative predictors of returning to work following primary total knee arthroplasty.

PubMed

Styron, Joseph F; Barsoum, Wael K; Smyth, Kathleen A; Singer, Mendel E

2011-01-05

There is little in the literature to guide clinicians in advising patients regarding their return to work following a primary total knee arthroplasty. In this study, we aimed to identify which factors are important in estimating a patient's time to return to work following primary total knee arthroplasty, how long patients can anticipate being off from work, and the types of jobs to which patients are able to return following primary total knee arthroplasty. A prospective cohort study was performed in which patients scheduled for a primary total knee arthroplasty completed a validated questionnaire preoperatively and at four to six weeks, three months, and six months postoperatively. The questionnaire assessed the patient's occupational physical demands, ability to perform job responsibilities, physical status, and motivation to return to work as well as factors that may impact his or her recovery and other workplace characteristics. Two survival analysis models were constructed to evaluate the time to return to work either at least part-time or full-time. Acceleration factors were calculated to indicate the relative percentage of time until the patient returned to work. The median time to return to work was 8.9 weeks. Patients who reported a sense of urgency about returning to work were found to return in half the time taken by other employees (acceleration factor = 0.468; p < 0.001). Other preoperative factors associated with a faster return to work included being female (acceleration factor = 0.783), self-employment (acceleration factor = 0.792), higher mental health scores (acceleration factor = 0.891), higher physical function scores (acceleration factor = 0.809), higher Functional Comorbidity Index scores (acceleration factor = 0.914), and a handicap accessible workplace (acceleration factor = 0.736). A slower return to work was associated with having less pain preoperatively (acceleration factor = 1.132), having a more physically demanding job (acceleration factor = 1.116), and receiving Workers' Compensation (acceleration factor = 4.360). Although the physical demands of a patient's job have a moderate influence on the patient's ability to return to work following a primary total knee arthroplasty, the patient's characteristics, particularly motivation, play a more important role.

Global Combat Support System-Marine Corps Logistics Chain Management Increment 1 (GCSS-MC LCM Inc 1)

DTIC Science & Technology

2016-03-01

Production Document DAE - Defense Acquisition Executive DoD - Department of Defense DoDAF - DoD Architecture Framework FD - Full Deployment FDD ...Jul 2004 Milestone B Jun 2007 Jun 2007 Milestone C May 2010 May 2010 FDD Sep 2014 Mar 2015 FD Dec 2015 Dec 2015 GCSS-MC LCM Inc 1 2016 MAR

Polishing Step Purification of High-Strength Wastewaters by Nanofiltration and Reverse Osmosis

PubMed Central

Zhou, Jinxiang; Baker, Brian O.; Grimsley, Charles T.; Husson, Scott M.

2016-01-01

This article reports findings on the use of nanofiltration (NF) and reverse osmosis (RO) for secondary treatment of high-strength rendering facility wastewaters following an ultrafiltration step. These wastewaters present significant challenges to classical treatment technologies. Constant-pressure, direct-flow membrane filtration experiments were done to screen for flux and effluent water permeate quality of ten commercial NF and RO membranes. All membranes tested were effective in reducing total dissolved salts (TDS) and chemical oxygen demand (COD); however, only two membranes (Koch MPF-34 and Toray 70UB) gave sufficiently stable flux values to warrant longer term cross-flow filtration studies. Cross-flow flux measurements, scanning electron microscopy (SEM), X-ray dispersive spectroscopy (EDS), and attenuated total reflectance-Fourier-transform infrared spectroscopy (ATR-FTIR) indicated that both membranes were eventually fouled by organic and inorganic foulants; however, the Toray 70UB RO membrane yielded a capacity of 1600 L/m2 prior to cleaning. A preliminary economic analysis compared the estimated costs of energy and consumables for a dual-stage UF/RO membrane process and dissolved air floatation (DAF) and found membrane process costs could be less than about 40% of the current DAF process. PMID:26978407

A genome-wide screen of bacterial mutants that enhance dauer formation in C. elegans.

PubMed

Khanna, Amit; Kumar, Jitendra; Vargas, Misha A; Barrett, LaKisha; Katewa, Subhash; Li, Patrick; McCloskey, Tom; Sharma, Amit; Naudé, Nicole; Nelson, Christopher; Brem, Rachel; Killilea, David W; Mooney, Sean D; Gill, Matthew; Kapahi, Pankaj

2016-12-13

Molecular pathways involved in dauer formation, an alternate larval stage that allows Caenorhabditis elegans to survive adverse environmental conditions during development, also modulate longevity and metabolism. The decision to proceed with reproductive development or undergo diapause depends on food abundance, population density, and temperature. In recent years, the chemical identities of pheromone signals that modulate dauer entry have been characterized. However, signals derived from bacteria, the major source of nutrients for C. elegans, remain poorly characterized. To systematically identify bacterial components that influence dauer formation and aging in C. elegans, we utilized the individual gene deletion mutants in E. coli (K12). We identified 56 diverse E. coli deletion mutants that enhance dauer formation in an insulin-like receptor mutant (daf-2) background. We describe the mechanism of action of a bacterial mutant cyaA, that is defective in the production of cyclic AMP, which extends lifespan and enhances dauer formation through the modulation of TGF-β (daf-7) signaling in C. elegans. Our results demonstrate the importance of bacterial components in influencing developmental decisions and lifespan in C. elegans. Furthermore, we demonstrate that C. elegans is a useful model to study bacterial-host interactions.

Characterisation of agroindustrial solid residues as biofuels and potential application in thermochemical processes.

PubMed

Virmond, Elaine; De Sena, Rennio F; Albrecht, Waldir; Althoff, Christine A; Moreira, Regina F P M; José, Humberto J

2012-10-01

In the present work, selected agroindustrial solid residues from Brazil - biosolids from meat processing wastewater treatment and mixture of sawdust with these biosolids; residues from apple and orange juice industries; sugarcane bagasse; açaí kernels (Euterpe oleracea) and rice husk - were characterised as solid fuels and an evaluation of their properties, including proximate and ultimate composition, energy content, thermal behaviour, composition and fusibility of the ashes was performed. The lower heating value of the biomasses ranged from 14.31 MJkg(-1) to 29.14 MJkg(-1), on a dry and ash free basis (daf), all presenting high volatile matter content, varying between 70.57 wt.% and 85.36 wt.% (daf) what improves the thermochemical conversion of the solids. The fouling and slagging tendency of the ashes was predicted based on the fuel ash composition and on the ash fusibility correlations proposed in the literature, which is important to the project and operation of biomass conversion systems. The potential for application of the Brazilian agroindustrial solid residues studied as alternative energy sources in thermochemical processes has been identified, especially concerning direct combustion for steam generation. Copyright © 2012 Elsevier Ltd. All rights reserved.

Function of RSKS-1-AAK-2-DAF-16 signaling cascade in enhancing toxicity of multi-walled carbon nanotubes can be suppressed by mir-259 activation in Caenorhabditis elegans

NASA Astrophysics Data System (ADS)

Zhuang, Ziheng; Li, Min; Liu, Hui; Luo, Libo; Gu, Weidong; Wu, Qiuli; Wang, Dayong

2016-08-01

Caenorhabditis elegans is an important non-mammalian alternative assay model for toxicological study. Previous study has indicated that exposure to multi-walled carbon nanotubes (MWCNTs) dysregulated the transcriptional expression of mir-259. In this study, we examined the molecular basis for mir-259 in regulating MWCNTs toxicity in nematodes. Mutation of mir-259 induced a susceptible property to MWCNTs toxicity, and MWCNTs exposure induced a significant increase in mir-259::GFP in pharyngeal/intestinal valve and reproductive tract, implying that mir-259 might mediate a protection mechanisms for nematodes against MWCNTs toxicity. RSKS-1, a putative ribosomal protein S6 kinase, acted as the target for mir-259 in regulating MWCNTs toxicity, and mutation of rsks-1 suppressed the susceptible property of mir-259 mutant to MWCNTs toxicity. Moreover, mir-259 functioned in pharynx-intestinal valve and RSKS-1 functioned in pharynx to regulate MWCNTs toxicity. Furthermore, RSKS-1 regulated MWCNTs toxicity by suppressing the function of AAK-2-DAF-16 signaling cascade. Our results will strengthen our understanding the microRNAs mediated protection mechanisms for animals against the toxicity from certain nanomaterials.

Fructan:fructan 1-fructosyltransferase and inulin hydrolase activities relating to inulin and soluble sugars in Jerusalem artichoke (Helianthus tuberosus Linn.) tubers during storage.

PubMed

Maicaurkaew, Sukanya; Jogloy, Sanun; Hamaker, Bruce R; Ningsanond, Suwayd

2017-03-01

Influences of harvest time and storage conditions on activities of fructan:fructan1-fructosyltransferase (1-FFT) and inulin hydrolase (InH) in relation to inulin and soluble sugars of Jerusalem artichoke ( Helianthus tuberosus L.) tubers were investigated. Maturity affected 1-FFT-activity, inulin contents, and inulin profiles of the tubers harvested between 30 and 70 days after flowering (DAF). Decreases in 1-FFT activity, high molecular weight inulin, and inulin content were observed in late-harvested tubers. The tubers harvested at 50 DAF had the highest inulin content (734.9 ± 20.5 g kg -1 DW) with a high degree of polymerization (28% of DP >30). During storage of the tubers, increases in InH activity (reached its peak at 15 days of storage) and gradual decreases in 1-FFT activity took placed. These changes were associated with inulin depolymerization, causing decreases in inulin content and increases in soluble sugars. As well, decreasing storage temperatures would retain high inulin content and keep low soluble sugars; and freezing at -18 °C would best retard 1-FFT, InH, and inulin changes.

Using lipidomics to reveal details of lipid accumulation in developing seeds from oilseed rape (Brassica napus L.).

PubMed

Woodfield, Helen K; Cazenave-Gassiot, Amaury; Haslam, Richard P; Guschina, Irina A; Wenk, Markus R; Harwood, John L

2018-03-01

With dwindling available agricultural land, concurrent with increased demand for oil, there is much current interest in raising oil crop productivity. We have been addressing this issue by studying the regulation of oil accumulation in oilseed rape (Brassica napus L). As part of this research we have carried out a detailed lipidomic analysis of developing seeds. The molecular species distribution in individual lipid classes revealed quite distinct patterns and showed where metabolic connections were important. As the seeds developed, the molecular species distributions changed, especially in the period of early (20days after flowering, DAF) to mid phase (27DAF) of oil accumulation. The patterns of molecular species of diacylglycerol, phosphatidylcholine and acyl-CoAs were used to predict the possible relative contributions of diacylglycerol acyltransferase (DGAT) and phospholipid:diacylglycerol acyltransferase to triacylglycerol production. Our calculations suggest that DGAT may hold a more important role in influencing the molecular composition of TAG. Enzyme selectivity had an important influence on the final molecular species patterns. Our data contribute significantly to our understanding of lipid accumulation in the world's third most important oil crop. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Germline Signals Deploy NHR-49 to Modulate Fatty-Acid β-Oxidation and Desaturation in Somatic Tissues of C. elegans

PubMed Central

Ratnappan, Ramesh; Amrit, Francis R. G.; Chen, Shaw-Wen; Gill, Hasreet; Holden, Kyle; Ward, Jordan; Yamamoto, Keith R.; Olsen, Carissa P.; Ghazi, Arjumand

2014-01-01

In C. elegans, removal of the germline extends lifespan significantly. We demonstrate that the nuclear hormone receptor, NHR-49, enables the response to this physiological change by increasing the expression of genes involved in mitochondrial β-oxidation and fatty-acid desaturation. The coordinated augmentation of these processes is critical for germline-less animals to maintain their lipid stores and to sustain de novo fat synthesis during adulthood. Following germline ablation, NHR-49 is up-regulated in somatic cells by the conserved longevity determinants DAF-16/FOXO and TCER-1/TCERG1. Accordingly, NHR-49 overexpression in fertile animals extends their lifespan modestly. In fertile adults, nhr-49 expression is DAF-16/FOXO and TCER-1/TCERG1 independent although its depletion causes age-related lipid abnormalities. Our data provide molecular insights into how reproductive stimuli are integrated into global metabolic changes to alter the lifespan of the animal. They suggest that NHR-49 may facilitate the adaptation to loss of reproductive potential through synchronized enhancement of fatty-acid oxidation and desaturation, thus breaking down some fats ordained for reproduction and orchestrating a lipid profile conducive for somatic maintenance and longevity. PMID:25474470

Empirical evidence for acceleration-dependent amplification factors

USGS Publications Warehouse

Borcherdt, R.D.

2002-01-01

Site-specific amplification factors, Fa and Fv, used in current U.S. building codes decrease with increasing base acceleration level as implied by the Loma Prieta earthquake at 0.1g and extrapolated using numerical models and laboratory results. The Northridge earthquake recordings of 17 January 1994 and subsequent geotechnical data permit empirical estimates of amplification at base acceleration levels up to 0.5g. Distance measures and normalization procedures used to infer amplification ratios from soil-rock pairs in predetermined azimuth-distance bins significantly influence the dependence of amplification estimates on base acceleration. Factors inferred using a hypocentral distance norm do not show a statistically significant dependence on base acceleration. Factors inferred using norms implied by the attenuation functions of Abrahamson and Silva show a statistically significant decrease with increasing base acceleration. The decrease is statistically more significant for stiff clay and sandy soil (site class D) sites than for stiffer sites underlain by gravely soils and soft rock (site class C). The decrease in amplification with increasing base acceleration is more pronounced for the short-period amplification factor, Fa, than for the midperiod factor, Fv.

Measuring the iron spectral opacity in solar conditions using a double ablation front scheme

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

Colaitis, A.; Ducret, J. E.; Turck-Chieze, S

We propose a new method to achieve hydrodynamic conditions relevant for the investigation of the radiation transport properties of the plasma at the base of the solar convection zone. The method is designed in the framework of opacity measurements with high-power lasers and exploits the temporal and spatial stability of hydrodynamic parameters in counter-propagating Double Ablation Front (DAF) structures.

Evaluation of Inventory Reduction Strategies: Balad Air Base Case Study

DTIC Science & Technology

2012-03-01

produced by conducting individual simulations using a unique random seed generated by the default Anylogic © random number generator. The...develops an agent-based simulation model of the sustainment supply chain supporting Balad AB during its closure using the software AnyLogic ®. The...research. The goal of USAF Stockage Policy is to maximize customer support while minimizing inventory costs (DAF, 2011:1). USAF stocking decisions

90-Day Inhalation Toxicity Study of Bio-Derived Gevo Alcohol-to-Jet (ATJ) Synthetic Paraffinic Kerosene (SPK) in Rats with Neurotoxicity Testing and Genotoxicity Assay

DTIC Science & Technology

2015-05-31

body weights, food consumption , and reproductive indices (vaginal cytology, sperm cell parameters). Neurobehavioral effects , evaluated by motor...Human Performance Wing Human Effectiveness Directorate Bioeffects Division Molecular Bioeffects Branch Wright-Patterson AFB OH 45433-5707...IV, DAF Chief, Bioeffects Division Human Effectiveness Directorate 711 th Human Perfmmance Wing Air Force Research Laboratmy This repmi is

Public Key Infrastructure Increment 2 (PKI Inc 2)

DTIC Science & Technology

2016-03-01

DoD - Department of Defense DoDAF - DoD Architecture Framework FD - Full Deployment FDD - Full Deployment Decision FY - Fiscal Year IA...experienced due to a delay in achieving the FDD . The Critical Change Report was provided to Congress on July 11, 2014. Firm, Fixed-Price Feasibility...to a delay in achieving the FDD . To support the Critical Change Report, the NSA Cost Estimating organization prepared a cost estimate that was

Teleport Generation 3 (Teleport Gen 3)

DTIC Science & Technology

2016-03-01

Department of Defense DoDAF - DoD Architecture Framework FD - Full Deployment FDD - Full Deployment Decision FY - Fiscal Year IA - Information...144A) reported since the previous MAIS Annual Report to Congress. The program recently achieved a FDD from the MDA on February 13, 2015. Teleport Gen 3...February 13, 2015 granting approval of the FDD . Acronyms and Abbreviations MLGC - MUOS to Legacy UHF SATCOM Gateway Component MOT&E - Multiservice

Base Information Transport Infrastructure Wired (BITI Wired)

DTIC Science & Technology

2016-03-01

Executive DoD - Department of Defense DoDAF - DoD Architecture Framework FD - Full Deployment FDD - Full Deployment Decision FY - Fiscal Year IA...Estimate has been accomplished this period leading to an approved Air Force Service Cost Position in support of the program’s December 2014 FDD milestone...validated to ensure alignment with the business case. This certification is based on my review of the December 2014 Service Cost Position and FDD

Leucine Modulation of the mTOR Pathway for Cognition Modulation: Kinetic and In Vitro Studies and Model Development

DTIC Science & Technology

2015-09-30

isoleucine non-polar L1 131 Aromatic side chain phenylalanine non-polar L1 165 tyrosine polar L1 181 tryptophan slightly...Human Performance Wing Human Effectiveness Directorate Bioeffects Division Molecular Bioeffects Branch Wright-Patterson AFB OH 45433-5707 NOTICE...IV, DAF Chief, Bioeffects Division Human Effectiveness Directorate 711th Human Performance Wing Air Force Research Laboratory This report is

Synthesis of nitric oxide in human osteoblasts in response to physiologic stimulation of electrotherapy.

PubMed

Hamed, Ayman; Kim, Paul; Cho, Michael

2006-12-01

Electrotherapy for bone healing, remodeling and wound healing may be mediated by modulation of nitric oxide (NO). Using NO-specific fluorophore (DAF-2), we report here that application of non-invasive, physiologic electrical stimulation induces NO synthesis in human osteoblasts, and that such NO generation is comparable to that induced by estrogen treatment. For example, application of a sinusoidal 1 Hz, 2 V/cm (peak to peak) electrical stimulation (ES) increases NO-bound DAF-2 fluorescence intensity by a 2-fold within 60 min exposure by activating nitric oxide synthase (NOS). Increase in the NO level is found to depend critically on the frequency and strength of ES. While the frequency of 1 Hz ES seems optimal, the ES strength >0.5 V/cm is required to induce significant NO increase, however. Nitric oxide synthesis in response to ES is completely prevented by blocking estrogen receptors using a competitive inhibitor, suggesting that NO generation is likely initiated by activation of estrogen receptors at the cell surface. Based on these findings, physiologic stimulation of electrotherapy appears to represent a potential non-invasive, non-genomic, and novel physical technique that could be used to regulate NO-mediated bone density and facilitate bone remodeling without adverse effects associated with hormone therapy.

Constitutive arginine-dependent nitric oxide synthase activity in different organs of pea seedlings during plant development.

PubMed

Corpas, Francisco J; Barroso, Juan B; Carreras, Alfonso; Valderrama, Raquel; Palma, José M; León, Ana M; Sandalio, Luisa M; del Río, Luis A

2006-07-01

Nitric oxide (NO) is an important signalling molecule in different animal and plant physiological processes. Little is known about its biological function in plants and on the enzymatic source or site of NO production during plant development. The endogenous NO production from L-arginine (NO synthase activity) was analyzed in leaves, stems and roots during plant development, using pea seedlings as a model. NOS activity was analyzed using a novel chemiluminescence-based assay which is more sensitive and specific than previous methods used in plant tissues. In parallel, NO accumulation was analyzed by confocal laser scanning microscopy using as fluorescent probes either DAF-2 DA or DAF-FM DA. A strong increase in NOS activity was detected in stems after 11 days growth, coinciding with the maximum stem elongation. The arginine-dependent NOS activity was constitutive and sensitive to aminoguanidine, a well-known irreversible inhibitor of animal NOS, and this NOS activity was differentially modulated depending on the plant organ and seedling developmental stage. In all tissues studied, NO was localized mainly in the vascular tissue (xylem) and epidermal cells and in root hairs. These loci of NO generation and accumulation suggest novel functions for NO in these cell types.

Low Temperature Extends the Lifespan of Bursaphelenchus xylophilus through the cGMP Pathway

PubMed Central

Wang, Bowen; Ma, Ling; Wang, Feng; Wang, Buyong; Hao, Xin; Xu, Jiayao; Ma, Yan

2017-01-01

The causal agent of pine wilt disease, pine wood nematode (PWN) (Bursaphelenchus xylophilus), revealed extended lifespan at low temperature. To discover the molecular mechanism of this phenomenon, we attempted to study the molecular characterization, transcript abundance, and functions of three genes of the cyclic guanosine monophosphate (cGMP) pathway from B. xylophilus. Three cGMP pathway genes were identified from B. xylophilus. Bioinformatic software was utilized to analyze the characteristics of the three putative proteins. Function of the three genes in cold tolerance was studied with RNA interference (RNAi). The results showed that the deduced protein of Bx-DAF-11 has an adenylate and guanylate cyclase catalytic domain, indicating an ability to bind to extracellular ligands and synthesizing cGMP. Both Bx-TAX-2 and Bx-TAX-4 have cyclic nucleotide-binding domains and ion transport protein domains, illustrating that they are cGMP-gated ion channels. The transcript level of Bx-daf-11, Bx-tax-2, and Bx-tax-4 increased at low temperature. The survival rates of three gene silenced B. xylophilus revealed a significant decrease at low temperature. This study illustrated that the cGMP pathway plays a key role in low-temperature-induced lifespan extension in B. xylophilus. PMID:29099744

On Using SysML, DoDAF 2.0 and UPDM to Model the Architecture for the NOAA's Joint Polar Satellite System (JPSS) Ground System (GS)

NASA Technical Reports Server (NTRS)

Hayden, Jeffrey L.; Jeffries, Alan

2012-01-01

The JPSS Ground System is a lIexible system of systems responsible for telemetry, tracking & command (TT &C), data acquisition, routing and data processing services for a varied lIeet of satellites to support weather prediction, modeling and climate modeling. To assist in this engineering effort, architecture modeling tools are being employed to translate the former NPOESS baseline to the new JPSS baseline, The paper will focus on the methodology for the system engineering process and the use of these architecture modeling tools within that process, The Department of Defense Architecture Framework version 2,0 (DoDAF 2.0) viewpoints and views that are being used to describe the JPSS GS architecture are discussed. The Unified Profile for DoOAF and MODAF (UPDM) and Systems Modeling Language (SysML), as ' provided by extensions to the MagicDraw UML modeling tool, are used to develop the diagrams and tables that make up the architecture model. The model development process and structure are discussed, examples are shown, and details of handling the complexities of a large System of Systems (SoS), such as the JPSS GS, with an equally complex modeling tool, are described

Accumulation of Phosphorus-Containing Compounds in Developing Seeds of Low-Phytate Pea (Pisum sativum L.) Mutants

PubMed Central

Shunmugam, Arun S.K.; Bock, Cheryl; Arganosa, Gene C.; Georges, Fawzy; Gray, Gordon R.; Warkentin, Thomas D.

2014-01-01

Low phytic acid (lpa) crops are low in phytic acid and high in inorganic phosphorus (Pi). In this study, two lpa pea genotypes, 1-150-81, 1-2347-144, and their progenitor CDC Bronco were grown in field trials for two years. The lpa genotypes were lower in IP6 and higher in Pi when compared to CDC Bronco. The total P concentration was similar in lpa genotypes and CDC Bronco throughout the seed development. The action of myo-inositol phosphate synthase (MIPS) (EC 5.5.1.4) is the first and rate-limiting step in the phytic acid biosynthesis pathway. Aiming at understanding the genetic basis of the lpa mutation in the pea, a 1530 bp open reading frame of MIPS was amplified from CDC Bronco and the lpa genotypes. Sequencing results showed no difference in coding sequence in MIPS between CDC Bronco and lpa genotypes. Transcription levels of MIPS were relatively lower at 49 days after flowering (DAF) than at 14 DAF for CDC Bronco and lpa lines. This study elucidated the rate and accumulation of phosphorus compounds in lpa genotypes. The data also demonstrated that mutation in MIPS was not responsible for the lpa trait in these pea lines. PMID:27135314

Mitoflash frequency in early adulthood predicts lifespan in Caenorhabditis elegans

NASA Astrophysics Data System (ADS)

Shen, En-Zhi; Song, Chun-Qing; Lin, Yuan; Zhang, Wen-Hong; Su, Pei-Fang; Liu, Wen-Yuan; Zhang, Pan; Xu, Jiejia; Lin, Na; Zhan, Cheng; Wang, Xianhua; Shyr, Yu; Cheng, Heping; Dong, Meng-Qiu

2014-04-01

It has been theorized for decades that mitochondria act as the biological clock of ageing, but the evidence is incomplete. Here we show a strong coupling between mitochondrial function and ageing by in vivo visualization of the mitochondrial flash (mitoflash), a frequency-coded optical readout reflecting free-radical production and energy metabolism at the single-mitochondrion level. Mitoflash activity in Caenorhabditis elegans pharyngeal muscles peaked on adult day 3 during active reproduction and on day 9 when animals started to die off. A plethora of genetic mutations and environmental factors inversely modified the lifespan and the day-3 mitoflash frequency. Even within an isogenic population, the day-3 mitoflash frequency was negatively correlated with the lifespan of individual animals. Furthermore, enhanced activity of the glyoxylate cycle contributed to the decreased day-3 mitoflash frequency and the longevity of daf-2 mutant animals. These results demonstrate that the day-3 mitoflash frequency is a powerful predictor of C. elegans lifespan across genetic, environmental and stochastic factors. They also support the notion that the rate of ageing, although adjustable in later life, has been set to a considerable degree before reproduction ceases.

Label-free proteome profiling reveals developmental-dependent patterns in young barley grains.

PubMed

Kaspar-Schoenefeld, Stephanie; Merx, Kathleen; Jozefowicz, Anna Maria; Hartmann, Anja; Seiffert, Udo; Weschke, Winfriede; Matros, Andrea; Mock, Hans-Peter

2016-06-30

Due to its importance as a cereal crop worldwide, high interest in the determination of factors influencing barley grain quality exists. This study focusses on the elucidation of protein networks affecting early grain developmental processes. NanoLC-based separation coupled to label-free MS detection was applied to gain insights into biochemical processes during five different grain developmental phases (pre-storage until storage phase, 3days to 16days after flowering). Multivariate statistics revealed two distinct developmental patterns during the analysed grain developmental phases: proteins showed either highest abundance in the middle phase of development - in the transition phase - or at later developmental stages - within the storage phase. Verification of developmental patterns observed by proteomic analysis was done by applying hypothesis-driven approaches, namely Western Blot analysis and enzyme assays. High general metabolic activity of the grain with regard to protein synthesis, cell cycle regulation, defence against oxidative stress, and energy production via photosynthesis was observed in the transition phase. Proteins upregulated in the storage phase are related towards storage protein accumulation, and interestingly to the defence of storage reserves against pathogens. A mixed regulatory pattern for most enzymes detected in our study points to regulatory mechanisms at the level of protein isoforms. In-depth understanding of early grain developmental processes of cereal caryopses is of high importance as they influence final grain weight and quality. Our knowledge about these processes is still limited, especially on proteome level. To identify key mechanisms in early barley grain development, a label-free data-independent proteomics acquisition approach has been applied. Our data clearly show, that proteins either exhibit highest expression during cellularization and the switch to the storage phase (transition phase, 5-7 DAF), or during storage product accumulation (10-16 DAF). The results highlight versatile cellular metabolic activity in the transition phase and strong convergence towards storage product accumulation in the storage phase. Notably, both phases are characterized by particular protective mechanism, such as scavenging of oxidative stress and defence against pathogens, during the transition and the storage phase, respectively. Copyright © 2016 Elsevier B.V. All rights reserved.

U.S. Army Workshop on Exploring Enterprise, System of Systems, System, and Software Architectures

DTIC Science & Technology

2009-03-01

state of a net-centric intelligence /surveillance/reconnaissance (ISR) capability featuring DCGS by the middle of the next decade.5 In some situations...boundaries. The DoDAF has a relatively long history. It started as a Command, Control, Communications, Computers, Surveillance and Intelligence ...Army have needed to perform tasks such as: col- lect and analyze intelligence information; maneuver the force; target and provide fire support; conduct

Theater Medical Information Program Joint Increment 2 (TMIP J Inc 2)

DTIC Science & Technology

2016-03-01

Acquisition Executive DoD - Department of Defense DoDAF - DoD Architecture Framework FD - Full Deployment FDD - Full Deployment Decision FY...the Full Deployment Decision ( FDD ), the TMIP-J Increment 2 Economic Analysis was approved on December 6, 2013. The USD(AT&L) signed an Acquisition...Decision Memorandum (ADM) on December 23, 2013 approving FDD for TMIP-J Increment 2 and establishing the Full Deployment Objective and Threshold dates as

Logistics Modernization Program Increment 2 (LMP Inc 2)

DTIC Science & Technology

2016-03-01

Executive DoD - Department of Defense DoDAF - DoD Architecture Framework FD - Full Deployment FDD - Full Deployment Decision FY - Fiscal Year IA...Documentation within the LMP Increment 2 MS C ADM, the LMP Increment 2 Business Case was updated for the FDD using change pages to remove information...following approval of the Army Cost Position being developed for the FDD . The LMP Increment 2 Business Case Change Pages were approved and signed by the

DEVS Unified Process for Web-Centric Development and Testing of System of Systems

DTIC Science & Technology

2008-05-20

gathering from the user. Further, methodologies have been developed to generate DEVS models from BPMN /BPEL-based and message-based requirement specifications...27] 3. BPMN /BPEL based system specifications: Business Process Modeling Notation ( BPMN ) [bpm] or Business Process Execution Language (BPEL) provide a...information is stored in .wsdl and .bpel files for BPEL but in proprietary format for BPMN . 4. DoDAF-based requirement specifications: Department of

Tailored Systems Architecture for Design of Space Science and Technology Missions Using DoDAF V2.0

DTIC Science & Technology

2009-12-01

programs do exist. Given the focus on rapid development and transition, if a system architecture framework could be developed and used to increase ...and scope are still being developed and refined at all levels within the DoD. As organizations have attempted to develop system architectures that...to produce architecture descriptions during the early-stages of system development. (3 p. 19) conformance, organizations ultimately using the

K-t GRAPPA-accelerated 4D flow MRI of liver hemodynamics: influence of different acceleration factors on qualitative and quantitative assessment of blood flow.

PubMed

Stankovic, Zoran; Fink, Jury; Collins, Jeremy D; Semaan, Edouard; Russe, Maximilian F; Carr, James C; Markl, Michael; Langer, Mathias; Jung, Bernd

2015-04-01

We sought to evaluate the feasibility of k-t parallel imaging for accelerated 4D flow MRI in the hepatic vascular system by investigating the impact of different acceleration factors. k-t GRAPPA accelerated 4D flow MRI of the liver vasculature was evaluated in 16 healthy volunteers at 3T with acceleration factors R = 3, R = 5, and R = 8 (2.0 × 2.5 × 2.4 mm(3), TR = 82 ms), and R = 5 (TR = 41 ms); GRAPPA R = 2 was used as the reference standard. Qualitative flow analysis included grading of 3D streamlines and time-resolved particle traces. Quantitative evaluation assessed velocities, net flow, and wall shear stress (WSS). Significant scan time savings were realized for all acceleration factors compared to standard GRAPPA R = 2 (21-71 %) (p < 0.001). Quantification of velocities and net flow offered similar results between k-t GRAPPA R = 3 and R = 5 compared to standard GRAPPA R = 2. Significantly increased leakage artifacts and noise were seen between standard GRAPPA R = 2 and k-t GRAPPA R = 8 (p < 0.001) with significant underestimation of peak velocities and WSS of up to 31 % in the hepatic arterial system (p <0.05). WSS was significantly underestimated up to 13 % in all vessels of the portal venous system for k-t GRAPPA R = 5, while significantly higher values were observed for the same acceleration with higher temporal resolution in two veins (p < 0.05). k-t acceleration of 4D flow MRI is feasible for liver hemodynamic assessment with acceleration factors R = 3 and R = 5 resulting in a scan time reduction of at least 40 % with similar quantitation of liver hemodynamics compared with GRAPPA R = 2.

10 Steps to Building an Architecture for Space Surveillance Projects

NASA Astrophysics Data System (ADS)

Gyorko, E.; Barnhart, E.; Gans, H.

Space surveillance is an increasingly complex task, requiring the coordination of a multitude of organizations and systems, while dealing with competing capabilities, proprietary processes, differing standards, and compliance issues. In order to fully understand space surveillance operations, analysts and engineers need to analyze and break down their operations and systems using what are essentially enterprise architecture processes and techniques. These techniques can be daunting to the first- time architect. This paper provides a summary of simplified steps to analyze a space surveillance system at the enterprise level in order to determine capabilities, services, and systems. These steps form the core of an initial Model-Based Architecting process. For new systems, a well defined, or well architected, space surveillance enterprise leads to an easier transition from model-based architecture to model-based design and provides a greater likelihood that requirements are fulfilled the first time. Both new and existing systems benefit from being easier to manage, and can be sustained more easily using portfolio management techniques, based around capabilities documented in the model repository. The resulting enterprise model helps an architect avoid 1) costly, faulty portfolio decisions; 2) wasteful technology refresh efforts; 3) upgrade and transition nightmares; and 4) non-compliance with DoDAF directives. The Model-Based Architecting steps are based on a process that Harris Corporation has developed from practical experience architecting space surveillance systems and ground systems. Examples are drawn from current work on documenting space situational awareness enterprises. The process is centered on DoDAF 2 and its corresponding meta-model so that terminology is standardized and communicable across any disciplines that know DoDAF architecting, including acquisition, engineering and sustainment disciplines. Each step provides a guideline for the type of data to collect, and also the appropriate views to generate. The steps include 1) determining the context of the enterprise, including active elements and high level capabilities or goals; 2) determining the desired effects of the capabilities and mapping capabilities against the project plan; 3) determining operational performers and their inter-relationships; 4) building information and data dictionaries; 5) defining resources associated with capabilities; 6) determining the operational behavior necessary to achieve each capability; 7) analyzing existing or planned implementations to determine systems, services and software; 8) cross-referencing system behavior to operational behavioral; 9) documenting system threads and functional implementations; and 10) creating any required textual documentation from the model.

Urinary tract infections of Escherichia coli strains of chaperone-usher system.

PubMed

Zalewska-Piatek, Beata M

2011-01-01

Urinary tract infections are a very serious health and economic problem affecting millions of people each year worldwide. The most common etiologic agent of this type of bacterial infections, involving the upper and lower urinary tract, are E. coli strains representing approximately 80% of cases. Uropathogenic E. coli strains produce several urovirulence factors which can be divided into two main types, surface virulence factors and exported virulence factors. Surface-exposed structures include mainly extracellular adhesive organelles such as fimbriae/pili necessary in adhesion, invasion, biofilm formation and cytokine induction. Among the surface-exposed polymeric adhesive structures there are three most invasive groups, type 1 pili, type P pili and Dr family of adhesins which are bioassembled via the conserved, among Gram-negative bacteria, chaperone-usher secretion system. Type 1 and P-piliated E. coli cause cystitis and pyelonephritis. The Dr family of adhesins recognizing DAF receptor is responsible for cystitis, pyelonephritis (especially in pregnant women) and diarrhoea (in infants). In addition, Dr-positive E. coli strains carry the risk of recurrent urinary tract infections. Pyelonephritis in pregnant women leads to a series of complications such as bacteremia, urosepsis, acute respiratory distress syndrome and even death. In the era of increasing drug resistance of bacteria, the development of vaccines, drugs termed pilicides and inhibitors of adhesion may be a promising tool in the fight against urogenital infections.

Visual Search in the Detection of Retinal Injury: A Feasibility Study

DTIC Science & Technology

2013-04-01

D, Heyes A. et al. Mobility of people with retinitis pigmentosa as a function of vision and psychological variables. Optometry and Vision Science...AFRL-RH-FS-TR-2013-0019 Visual Search in the Detection of Retinal Injury: A Feasibility Study Thomas Kuyk TASC, Inc. Lei Liu The...Detection of Retinal Injury: A Feasibility Study" 2013 0019 LEON N. McLIN, JR., DR-III, DAF Work Unit Manager 711 HPW/ RHDO POLHAMUS.GARR ETT.D

On the Use of Literary Texts in the Daf Lesson with the Example of Heinrich Boell's Short Story "Die Blasse Anna" with a Focus on Writing on a B2 Level

ERIC Educational Resources Information Center

Ghorabi, Yassamin Ostad A.; Haddadi, Mohammad Hossein

2017-01-01

For the promotion and optimization of teaching foreign languages, new methods and strategies are always considered that include literary texts. The aim of the present paper is to provide arguments for the use of literature in the classroom. Learning target areas and selection criteria for the use of literary texts in the classroom are presented. A…

Joint Space Operations Center (JSpOC) Mission System Increment 2 (JMS Inc 2)

DTIC Science & Technology

2016-03-01

Defense Acquisition Executive DoD - Department of Defense DoDAF - DoD Architecture Framework FD - Full Deployment FDD - Full Deployment Decision FY...date has slipped from September 2016 to December 2016 and FDD has slipped from October 2016 to March 2017 since the last MAIS Annual Report...testing. This added test time, in combination with funding reductions and the US Government furlough and shutdown in FY13, caused a total FDD slip

Distributed Common Ground System Army Increment 1 (DCGS-A Inc 1)

DTIC Science & Technology

2016-03-01

Acquisition Executive DoD - Department of Defense DoDAF - DoD Architecture Framework FD - Full Deployment FDD - Full Deployment Decision FY - Fiscal...updated prior to the FDD ITAB in December 2012 and provided additional COA analysis/validation referenced in the FDD ADM (December 14, 2012) and FDD ...required by 10 U.S.C. 2334(a)(6). The Army Cost Review Board developed the FDD Army Cost Position (ACP), dated October 19, 2012, through the update of

Mission Planning System Increment 5 (MPS Inc 5)

DTIC Science & Technology

2016-03-01

DoD - Department of Defense DoDAF - DoD Architecture Framework FD - Full Deployment FDD - Full Deployment Decision FY - Fiscal Year IA...Alternative Selected (Funds First Obligated (FFO)) (O/T) : Mar 2013 / Mar 2013 • MS B (O/T) : Apr 2012 / Apr 2012 • MS C (O/T) : N/A / N/A • FDD (O/T...Deployed Software Intensive Program" as described in the DOD Instruction 5000.02, January 7, 2015. 4. FDD provides approval to field the

Air and Space Operations Center-Weapon System Increment 10.2 (AOC-WS Inc 10.2)

DTIC Science & Technology

2016-03-01

DAE - Defense Acquisition Executive DoD - Department of Defense DoDAF - DoD Architecture Framework FD - Full Deployment FDD - Full Deployment...the AOC 10.2 MAIS was approximately 11 months beyond the original schedule estimates for MS-C, July 31, 2015, and FDD , July 31, 2016. Accordingly...ADM effectively acknowledged selection of AOC-WS Inc 10.2 as the Preferred Alternative, thereby starting the 5-year development window to attain FDD

Strukturen und Geschäftsmodelle eines neuen Energiemarkts

NASA Astrophysics Data System (ADS)

Mildebrath, Bernhard

Die Energiewende fördert nicht nur technologische, sondern auch organisatorische und kommerzielle Innovationen. Die Strukturen und Geschäftsmodelle eines neuen Energiemarktes entwickeln sich bereits. Im Spagat zwischen Versuch und Irrtum werden sie völlig neue Lösungen für eine altbekannte Forderung schaffen: Strom soll preiswert, sicher und umweltverträglich sein. Der nachstehende Artikel präsentiert dafür - teils zugespitzte - Überlegungen zu den Strukturen und Geschäftsmodellen eines neuen Energiemarkts.

The unfolded protein response in a pair of sensory neurons promotes entry of C. elegans into dauer diapause.

PubMed

Kulalert, Warakorn; Kim, Dennis H

2013-12-16

In response to unfavorable environmental conditions such as starvation, crowding, and elevated temperature, Caenorhabditis elegans larvae enter an alternative developmental stage known as dauer, which is characterized by adaptive changes in stress resistance and metabolism. The genetic dissection of the molecular mechanisms of the C. elegans dauer developmental decision has defined evolutionarily conserved signaling pathways of organismal neuroendocrine physiology. Here, we have identified a mechanism by which a dominant mutation in a neuronal insulin gene, daf-28(sa191), causes constitutive entry into dauer diapause. We demonstrate that expression of the mutant DAF-28 insulin peptide results in endoplasmic reticulum (ER) stress in the ASI pair of chemosensory neurons. The neuronal ER stress does not compromise cellular survival but activates PEK-1, the C. elegans ortholog of the mammalian eIF2α kinase PERK, which in turn phosphorylates Ser49 of eIF2α, specifically in the ASI neuron pair, to promote entry into dauer diapause. Our data establish a novel role for ER stress and the unfolded protein response (UPR) in promoting entry into dauer diapause and suggest that, in addition to cell-autonomous activities in the maintenance of ER homeostasis, the UPR may act in a non-cell-autonomous manner to promote organismal adaptation to stress during larval development. Copyright © 2013 Elsevier Ltd. All rights reserved.

Survey of dissolved air flotation system efficiency for reduce of pollution of vegetable oil industry wastewater.

PubMed

Keramati, H; Alidadi, H; Parvaresh, A R; Movahedian, H; Mahvi, A H

2008-10-01

The aim of this research was to sudy the reduction of pollution of vegetable oil manufacturing wastewater with DAF system. At first phase of this examination, the optimum dosage of the coagulants was determined. The coagulants that used in this study were Alum and Ferric Chloride. The second phase was flotation in this series of examinations, oil, COD, total solid, volatile solid, fixed solid and suspended solid measured in raw wastewater and the effluent of the DAF pilot. Optimum value of pH for alum and ferric chloride obtained 7.5 and 5.5, respectively. Optimum dosage for these obtained 30 and 32 mg L(-1) in this research. Mean removal for the parameters ofoil, COD, total solid, volatile solid, fixed solid and suspended solid obtained 75.85, 78.27, 77.32, 82.47, 73.52 and 85.53%, respectively. With pressure rising from 3 to 4 and 5 atm removing rate of COD, total solid, volatile solid, fixed solid parameters reduced, but oil and suspended solid have increase. In addition, following increase of flotation time up to 120 sec all of the measured parameters have increase in removing rate. Optimum A/S for removal of COD, total solid, volatile solid, fixed solid parameters obtained 0.001 and for oil and suspended solid obtained 0.0015.

Hormone-mediated growth dynamics of the barley pericarp as revealed by magnetic resonance imaging and transcript profiling

PubMed Central

Pielot, Rainer; Kohl, Stefan; Manz, Bertram; Rutten, Twan; Weier, Diana; Tarkowská, Danuše; Rolčík, Jakub; Strnad, Miroslav; Volke, Frank; Weber, Hans

2015-01-01

The shape of the maternal pericarp affects cereal grain mass and yield. Pericarp growth was analysed by magnetic resonance imaging (MRI), revealing topological maps of mobile water in developing pericarp of barley (Hordeum vulgare) and displaying tissue regions actively elongating in specific temporal–spatial patterns. Correlation analysis of MRI signals and growth rates reveals that growth in length is mediated by dorsal and also lateral rather than ventral regions. Growth in thickness is related to ventral regions. Switching from dorsal to ventral growth is associated with differential expression of axial regulators of the HD-ZipIII and Kanadi/Ettin types, and NPH3 photoreceptors, suggesting light-mediated auxin re-distribution. Auxin increases with the highest levels in the basal pericarp at 6 days after fertilization (DAF), together with transcriptionally up-regulated auxin transport and signalling. Gibberellin biosynthesis is transcriptionally up-regulated only later, and levels of bioactive gibberellins increase from 7 to 13 DAF, with higher levels in ventral than dorsal regions. Differential gene expression related to cell expansion indicates genes related to apoplast acidification, wall relaxation, sugar cleavage, water transport, and cell wall biosynthesis. Candidate genes potentially involved in pericarp extension are distinguished by their temporal expression, representing potential isoforms responsible for dorsal-mediated early growth in length or ventral-mediated late growth in thickness. PMID:26276866

Bottlenecks in erucic acid accumulation in genetically engineered ultrahigh erucic acid Crambe abyssinica

PubMed Central

Guan, Rui; Lager, Ida; Li, Xueyuan; Stymne, Sten; Zhu, Li-Hua

2014-01-01

Erucic acid is a valuable industrial fatty acid with many applications. The main producers of this acid are today high erucic rapeseed (Brassica napus) and mustard (Brassica juncea), which have 45%–50% of erucic acid in their seed oils. Crambe abyssinica is an alternative promising producer of this acid as it has 55%–60% of erucic acid in its oil. Through genetic modification (GM) of three genes, we have previously increased the level of erucic acid to 71% (68 mol%) in Crambe seed oil. In this study, we further investigated different aspects of oil biosynthesis in the developing GM Crambe seeds in comparison with wild-type (Wt) Crambe, rapeseed and safflower (Carthamus tinctorius). We show that Crambe seeds have very low phosphatidylcholine-diacylglycerol interconversion, suggesting it to be the main reason why erucic acid is limited in the membrane lipids during oil biosynthesis. We further show that GM Crambe seeds have slower seed development than Wt, accompanied by slower oil accumulation during the first 20 days after flowering (DAF). Despite low accumulation of erucic acid during early stages of GM seed development, nearly 86 mol% of all fatty acids accumulated between 27 and 50 DAF was erucic acid, when 40% of the total oil is laid down. Likely bottlenecks in the accumulation of erucic acid during early stages of GM Crambe seed development are discussed. PMID:24119222

Breast cancer detection using time reversal

NASA Astrophysics Data System (ADS)

Sheikh Sajjadieh, Mohammad Hossein

Breast cancer is the second leading cause of cancer death after lung cancer among women. Mammography and magnetic resonance imaging (MRI) have certain limitations in detecting breast cancer, especially during its early stage of development. A number of studies have shown that microwave breast cancer detection has potential to become a successful clinical complement to the conventional X-ray mammography. Microwave breast imaging is performed by illuminating the breast tissues with an electromagnetic waveform and recording its reflections (backscatters) emanating from variations in the normal breast tissues and tumour cells, if present, using an antenna array. These backscatters, referred to as the overall (tumour and clutter) response, are processed to estimate the tumour response, which is applied as input to array imaging algorithms used to estimate the location of the tumour. Due to changes in the breast profile over time, the commonly utilized background subtraction procedures used to estimate the target (tumour) response in array processing are impractical for breast cancer detection. The thesis proposes a new tumour estimation algorithm based on a combination of the data adaptive filter with the envelope detection filter (DAF/EDF), which collectively do not require a training step. After establishing the superiority of the DAF/EDF based approach, the thesis shows that the time reversal (TR) array imaging algorithms outperform their conventional conterparts in detecting and localizing tumour cells in breast tissues at SNRs ranging from 15 to 30dB.

A Distributed Chemosensory Circuit for Oxygen Preference in C. elegans

PubMed Central

Chang, Andy J; Chronis, Nikolas; Karow, David S; Marletta, Michael A; Bargmann, Cornelia I

2006-01-01

The nematode Caenorhabditis elegans has complex, naturally variable behavioral responses to environmental oxygen, food, and other animals. C. elegans detects oxygen through soluble guanylate cyclase homologs (sGCs) and responds to it differently depending on the activity of the neuropeptide receptor NPR-1: npr-1(lf) and naturally isolated npr-1(215F) animals avoid high oxygen and aggregate in the presence of food; npr-1(215V) animals do not. We show here that hyperoxia avoidance integrates food with npr-1 activity through neuromodulation of a distributed oxygen-sensing network. Hyperoxia avoidance is stimulated by sGC-expressing oxygen-sensing neurons, nociceptive neurons, and ADF sensory neurons. In npr-1(215V) animals, the switch from weak aerotaxis on food to strong aerotaxis in its absence requires close regulation of the neurotransmitter serotonin in the ADF neurons; high levels of ADF serotonin promote hyperoxia avoidance. In npr-1(lf) animals, food regulation is masked by increased activity of the oxygen-sensing neurons. Hyperoxia avoidance is also regulated by the neuronal TGF-β homolog DAF-7, a secreted mediator of crowding and stress responses. DAF-7 inhibits serotonin synthesis in ADF, suggesting that ADF serotonin is a convergence point for regulation of hyperoxia avoidance. Coalitions of neurons that promote and repress hyperoxia avoidance generate a subtle and flexible response to environmental oxygen. PMID:16903785

10-Hydroxy-2-decenoic Acid, the Major Lipid Component of Royal Jelly, Extends the Lifespan of Caenorhabditis elegans through Dietary Restriction and Target of Rapamycin Signaling.

PubMed

Honda, Yoko; Araki, Yoko; Hata, Taketoshi; Ichihara, Kenji; Ito, Masafumi; Tanaka, Masashi; Honda, Shuji

2015-01-01

Royal jelly (RJ) produced by honeybees has been reported to possess diverse health-beneficial properties and has been implicated to have a function in longevity across diverse species as well as honeybees. 10-Hydroxy-2-decenoic acid (10-HDA), the major lipid component of RJ produced by honeybees, was previously shown to increase the lifespan of Caenorhabditis elegans. The objective of this study is to elucidate signaling pathways that are involved in the lifespan extension by 10-HDA. 10-HDA further extended the lifespan of the daf-2 mutants, which exhibit long lifespan through reducing insulin-like signaling (ILS), indicating that 10-HDA extended lifespan independently of ILS. On the other hand, 10-HDA did not extend the lifespan of the eat-2 mutants, which show long lifespan through dietary restriction caused by a food-intake defect. This finding indicates that 10-HDA extends lifespan through dietary restriction signaling. We further found that 10-HDA did not extend the lifespan of the long-lived mutants in daf-15, which encodes Raptor, a target of rapamycin (TOR) components, indicating that 10-HDA shared some longevity control mechanisms with TOR signaling. Additionally, 10-HDA was found to confer tolerance against thermal and oxidative stress. 10-HDA increases longevity not through ILS but through dietary restriction and TOR signaling in C. elegans.

10-Hydroxy-2-decenoic Acid, the Major Lipid Component of Royal Jelly, Extends the Lifespan of Caenorhabditis elegans through Dietary Restriction and Target of Rapamycin Signaling

PubMed Central

Honda, Yoko; Araki, Yoko; Hata, Taketoshi; Ichihara, Kenji; Ito, Masafumi; Tanaka, Masashi; Honda, Shuji

2015-01-01

Royal jelly (RJ) produced by honeybees has been reported to possess diverse health-beneficial properties and has been implicated to have a function in longevity across diverse species as well as honeybees. 10-Hydroxy-2-decenoic acid (10-HDA), the major lipid component of RJ produced by honeybees, was previously shown to increase the lifespan of Caenorhabditis elegans. The objective of this study is to elucidate signaling pathways that are involved in the lifespan extension by 10-HDA. 10-HDA further extended the lifespan of the daf-2 mutants, which exhibit long lifespan through reducing insulin-like signaling (ILS), indicating that 10-HDA extended lifespan independently of ILS. On the other hand, 10-HDA did not extend the lifespan of the eat-2 mutants, which show long lifespan through dietary restriction caused by a food-intake defect. This finding indicates that 10-HDA extends lifespan through dietary restriction signaling. We further found that 10-HDA did not extend the lifespan of the long-lived mutants in daf-15, which encodes Raptor, a target of rapamycin (TOR) components, indicating that 10-HDA shared some longevity control mechanisms with TOR signaling. Additionally, 10-HDA was found to confer tolerance against thermal and oxidative stress. 10-HDA increases longevity not through ILS but through dietary restriction and TOR signaling in C. elegans. PMID:25789174

Final Report for Bio-Inspired Approaches to Moving-Target Defense Strategies

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

Fink, Glenn A.; Oehmen, Christopher S.

This report records the work and contributions of the NITRD-funded Bio-Inspired Approaches to Moving-Target Defense Strategies project performed by Pacific Northwest National Laboratory under the technical guidance of the National Security Agency’s R6 division. The project has incorporated a number of bio-inspired cyber defensive technologies within an elastic framework provided by the Digital Ants. This project has created the first scalable, real-world prototype of the Digital Ants Framework (DAF)[11] and integrated five technologies into this flexible, decentralized framework: (1) Ant-Based Cyber Defense (ABCD), (2) Behavioral Indicators, (3) Bioinformatic Clas- sification, (4) Moving-Target Reconfiguration, and (5) Ambient Collaboration. The DAF canmore » be used operationally to decentralize many such data intensive applications that normally rely on collection of large amounts of data in a central repository. In this work, we have shown how these component applications may be decentralized and may perform analysis at the edge. Operationally, this will enable analytics to scale far beyond current limitations while not suffering from the bandwidth or computational limitations of centralized analysis. This effort has advanced the R6 Cyber Security research program to secure digital infrastructures by developing a dynamic means to adaptively defend complex cyber systems. We hope that this work will benefit both our client’s efforts in system behavior modeling and cyber security to the overall benefit of the nation.« less

Effect of delayed auditory feedback on stuttering with and without central auditory processing disorders.

PubMed

Picoloto, Luana Altran; Cardoso, Ana Cláudia Vieira; Cerqueira, Amanda Venuti; Oliveira, Cristiane Moço Canhetti de

2017-12-07

To verify the effect of delayed auditory feedback on speech fluency of individuals who stutter with and without central auditory processing disorders. The participants were twenty individuals with stuttering from 7 to 17 years old and were divided into two groups: Stuttering Group with Auditory Processing Disorders (SGAPD): 10 individuals with central auditory processing disorders, and Stuttering Group (SG): 10 individuals without central auditory processing disorders. Procedures were: fluency assessment with non-altered auditory feedback (NAF) and delayed auditory feedback (DAF), assessment of the stuttering severity and central auditory processing (CAP). Phono Tools software was used to cause a delay of 100 milliseconds in the auditory feedback. The "Wilcoxon Signal Post" test was used in the intragroup analysis and "Mann-Whitney" test in the intergroup analysis. The DAF caused a statistically significant reduction in SG: in the frequency score of stuttering-like disfluencies in the analysis of the Stuttering Severity Instrument, in the amount of blocks and repetitions of monosyllabic words, and in the frequency of stuttering-like disfluencies of duration. Delayed auditory feedback did not cause statistically significant effects on SGAPD fluency, individuals with stuttering with auditory processing disorders. The effect of delayed auditory feedback in speech fluency of individuals who stutter was different in individuals of both groups, because there was an improvement in fluency only in individuals without auditory processing disorder.

Susceptibility of materials processing experiments to low-level accelerations

NASA Technical Reports Server (NTRS)

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.

Neutron dose per fluence and weighting factors for use at high energy accelerators

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

Cossairt, J.Donald; Vaziri, Kamran; /Fermilab

2008-07-01

In June 2007, the United States Department of Energy incorporated revised values of neutron weighting factors into its occupational radiation protection Regulation 10 CFR Part 835 as part of updating its radiation dosimetry system. This has led to a reassessment of neutron radiation fields at high energy proton accelerators such as those at the Fermi National Accelerator Laboratory (Fermilab). Values of dose per fluence factors appropriate for accelerator radiation fields calculated elsewhere are collated and radiation weighting factors compared. The results of this revision to the dosimetric system are applied to americium-beryllium neutron energy spectra commonly used for instrument calibrations.more » A set of typical accelerator neutron energy spectra previously measured at Fermilab are reassessed in light of the new dosimetry system. The implications of this revision are found to be of moderate significance.« less

Evaluation of slice accelerations using multiband echo planar imaging at 3 Tesla

PubMed Central

Xu, Junqian; Moeller, Steen; Auerbach, Edward J.; Strupp, John; Smith, Stephen M.; Feinberg, David A.; Yacoub, Essa; Uğurbil, Kâmil

2013-01-01

We evaluate residual aliasing among simultaneously excited and acquired slices in slice accelerated multiband (MB) echo planar imaging (EPI). No in-plane accelerations were used in order to maximize and evaluate achievable slice acceleration factors at 3 Tesla. We propose a novel leakage (L-) factor to quantify the effects of signal leakage between simultaneously acquired slices. With a standard 32-channel receiver coil at 3 Tesla, we demonstrate that slice acceleration factors of up to eight (MB = 8) with blipped controlled aliasing in parallel imaging (CAIPI), in the absence of in-plane accelerations, can be used routinely with acceptable image quality and integrity for whole brain imaging. Spectral analyses of single-shot fMRI time series demonstrate that temporal fluctuations due to both neuronal and physiological sources were distinguishable and comparable up to slice-acceleration factors of nine (MB = 9). The increased temporal efficiency could be employed to achieve, within a given acquisition period, higher spatial resolution, increased fMRI statistical power, multiple TEs, faster sampling of temporal events in a resting state fMRI time series, increased sampling of q-space in diffusion imaging, or more quiet time during a scan. PMID:23899722

Propagation of 3-D Beams Using a Finite-Difference Algorithm: Practical Considerations

DTIC Science & Technology

2011-05-22

electric-discharge laser ,” J. Appl. Phys. 49(3), 1012–1027 (1978). [6] Sziklas, E. A. and Siegman , A. E., “Mode calculations in unstable resonators with...flowing saturable gain .2. fast fourier-transform method,” Applied Optics 14(8), 1874–1889 (1975). [7] Siegman , A. E., [ Lasers ], University Science...Signed// ALAN H. PAXTON, DR-III Project Manager //Signed// MICHAEL F. SHEEHAN, DR-III, DAF Acting Chief, Laser Division This report is published in

The Differential Vector Phase-Locked Loop for Global Navigation Satellite System Signal Tracking

DTIC Science & Technology

2014-06-01

DAF Approved: //signed// John F. Raquet, PhD (Chairman) //signed// Mark E. Oxley, PhD (Member) //signed// Maj Marshall E. Haker , PhD (Member) 16 May...busy as you keep yourself. Dr. Mark Oxley and Dr. Marshall Haker for your sage guidance as members of my committee. Dr. Ken Fisher for making Kalman...Raquet, Dr. Marshall Haker , and Mr. Ben Downing at AFIT, following notes for Dr. Raquet’s Advanced GPS Receiver Design class. The second type was RINEX

integrated Electronic Health Record Increment 1 (iEHR Inc 1)

DTIC Science & Technology

2016-03-01

Executive DoD - Department of Defense DoDAF - DoD Architecture Framework FD - Full Deployment FDD - Full Deployment Decision FY - Fiscal Year IA...Acronyms and Abbreviations ADM - Acquisition Decision Memorandum FD - Full Deployment FDD - Full Deployment Decision iEHR Inc 1 2016 MAR UNCLASSIFIED...iEHR Increment 1 APB for FDD achieved in November 2014 was signed by the MDA March 2, 2015. Current estimate is consistent with the FDD APB. iEHR Inc 1 2016 MAR UNCLASSIFIED 11

Global Combat Support System Army Increment 1 (GCSS-A Inc 1)

DTIC Science & Technology

2016-03-01

Acquisition Executive DoD - Department of Defense DoDAF - DoD Architecture Framework FD - Full Deployment FDD - Full Deployment Decision FY - Fiscal Year...another economic anaylsis was completed on November 14, 2012, in advance of a successful FDD . The program is now in the O&S Phase. GCSS-A Inc 1 2016...Increment I Feb 2011 Aug 2011 Full Deployment Decision ( FDD )1 Feb 2012 Dec 2012 Full Deployment (FD)2 Sep 2017 Mar 2018 Memo 1/ GCSS-A Increment 1

Divisional Electronic Warfare Combat (DEWCOM) Model - User Manual.

DTIC Science & Technology

1980-09-01

ulated combat hours. DTIC TA% 1~ Il m I UNCLASSIFIED SIECURITY CLASSIFICATION Or THIS PAGEft7n Date Entered) 4 ’ ./ .7"* t l DIVISIONAL ELECTRONIC WARFARE...277 4.2.1 Report M (Unit Status) ....... .......................... 277 4.2.2 Report M2 (Link Status...NONE in the first 4 spaces. 27 Mai -RF DEWCOM M S aoNE_ DAF INPUT DATA PREPARATI toI 2 4 . 8 1() 1 12 ,1 14 15 1 1718 lq2n2122 21242526 2728293031 3233

Business Case Analysis for the Versatile Depot Automated Test Station Used in the USAF Warner Robins Air Logistics Center Maintenance Depot

DTIC Science & Technology

2008-06-01

executes the avionics test) can run on the new ATS thus creating the common ATS framework . The system will also enable numerous new functional...Enterprise-level architecture that reflects corporate DoD priorities and requirements for business systems, and provides a common framework to ensure that...entire Business Mission Area (BMA) of the DoD. The BEA also contains a set of integrated Department of Defense Architecture Framework (DoDAF

Tailored Systems Architecture for Design of Space Science and Technology Missions Using DoDAF V2.0

DTIC Science & Technology

2009-12-01

GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND...ADDRESS(ES) Air Force Institute of Technology,2950 Hobson Way,WPAFB,OH,45433-7765 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING...the focus on rapid development and transition, if a system architecture framework could be developed and used to increase visibility within the

Tailored Systems Architecture for Design of Space Science and Technology Missions using DoDAF V2.0

DTIC Science & Technology

2009-12-01

GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND...ADDRESS(ES) Air Force Institute of Technology,2950 Hobson Way,WPAFB,OH,45433-7765 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING...the focus on rapid development and transition, if a system architecture framework could be developed and used to increase visibility within the

Teacher Attitudes toward Subject-Specific Acceleration: Instrument Development and Validation

ERIC Educational Resources Information Center

Rambo, Karen E.; McCoach, D. Betsy

2012-01-01

Despite the research supporting acceleration, some teachers are still hesitant to recommend acceleration for advanced students. The Teacher Attitudes Toward Subject-Specific Acceleration (TATSSA) instrument was designed to uncover the factors that influence teacher decisions to recommend students for subject-specific acceleration. First, we…

Incorporation of Prior Knowledge of Signal Behavior Into the Reconstruction to Accelerate the Acquisition of Diffusion MRI Data.

PubMed

Abascal, Juan F P J; Desco, Manuel; Parra-Robles, Juan

2018-02-01

Diffusion MRI data are generally acquired using hyperpolarized gases during patient breath-hold, which yields a compromise between achievable image resolution, lung coverage, and number of -values. In this paper, we propose a novel method that accelerates the acquisition of diffusion MRI data by undersampling in both the spatial and -value dimensions and incorporating knowledge about signal decay into the reconstruction (SIDER). SIDER is compared with total variation (TV) reconstruction by assessing its effect on both the recovery of ventilation images and the estimated mean alveolar dimensions (MADs). Both methods are assessed by retrospectively undersampling diffusion data sets ( =8) of healthy volunteers and patients with Chronic Obstructive Pulmonary Disease (COPD) for acceleration factors between x2 and x10. TV led to large errors and artifacts for acceleration factors equal to or larger than x5. SIDER improved TV, with a lower solution error and MAD histograms closer to those obtained from fully sampled data for acceleration factors up to x10. SIDER preserved image quality at all acceleration factors, although images were slightly smoothed and some details were lost at x10. In conclusion, we developed and validated a novel compressed sensing method for lung MRI imaging and achieved high acceleration factors, which can be used to increase the amount of data acquired during breath-hold. This methodology is expected to improve the accuracy of estimated lung microstructure dimensions and provide more options in the study of lung diseases with MRI.

Social-Emotional Characteristics of Gifted Accelerated and Non-Accelerated Students in the Netherlands

ERIC Educational Resources Information Center

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

2012-01-01

Background: 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. Aims: In this study, social-emotional characteristics of accelerated…

Physics of Limiting Phenomena in Superconducting Microwave Resonators: Vortex Dissipation, Ultimate Quench and Quality Factor Degradation Mechanisms

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

Checchin, Mattia

Superconducting niobium accelerating cavities are devices operating in radio-frequency and able to accelerate charged particles up to energy of tera-electron-volts. Such accelerating structures are though limited in terms of quality factor and accelerating gradient, that translates--in some cases--in higher capital costs of construction and operation of superconducting rf accelerators. Looking forward for a new generation of more affordable accelerators, the physical description of limiting mechanisms in superconducting microwave resonators is discussed. In particular, the physics behind the dissipation introduced by vortices in the superconductor, the ultimate quench limitations and the quality factor degradation mechanism after a quench are described inmore » detail. One of the limiting factor of the quality factor is the dissipation introduced by trapped magnetic flux vortices. The radio-frequency complex response of trapped vortices in superconductors is derived by solving the motion equation for a magnetic flux line, assuming a bi-dimensional and mean free path-dependent Lorentzian-shaped pinning potential. The resulting surface resistance shows the bell-shaped trend as a function of the mean free path, in agreement with the experimental data observed. Such bell-shaped trend of the surface resistance is described in terms of the interplay of the two limiting regimes identified as pinning and flux flow regimes, for low and large mean free path values respectively. The model predicts that the dissipation regime--pinning- or flux-flow-dominated--can be tuned either by acting on the frequency or on the electron mean free path value. The effect of different configurations of pinning sites and strength on the vortex surface resistance are also discussed. Accelerating cavities are also limited by the quench of the superconductive state, which limits the maximum accelerating gradient achievable. The accelerating field limiting factor is usually associate d to the superheating field, which is intimately correlated to the penetration of magnetic flux vortices in the material. Experimental data for N-doped cavities suggest that uniform Ginzburg-Landau parameter cavities are statistically limited by the lower critical field, in terms of accelerating gradient. By introducing a Ginzburg-Landau parameter profile at the cavity rf surface--dirty layer--the accelerating gradient of superconducting resonators can be enhanced. The description of the physics behind the accelerating gradient enhancement as a consequence of the dirty layer is carried out by solving numerically the Ginzburg-Landau equations for the layered system. The enhancement is showed to be promoted by the higher energy barrier to vortex penetration, and by the enhanced lower critical field. Another serious threat to the quality factor during the cavity operation is the extra dissipation introduced by the quench. Such quality factor degradation mechanism due to the quench, is generated by the trapping of external magnetic flux at quench spot. The purely extrinsic origin of such extra dissipation is proven by the impossibility of decrease the quality factor by quenching in a magnetic field-free environment. Also, a clear relation of the dissipation introduced by quenching to the orientation of the applied magnetic field is observed. The full recover of the quality factor by re-quenching in compensated field is possible when the trapped flux at the quench spot is modest. On the contrary, when the trapped magnetic flux is too large, the quality factor degradation may become irreversible by this technique, likely due to the outward flux migration beyond the normal zone opening during the quench.« less

Physics of limiting phenomena in superconducting microwave resonators: Vortex dissipation, ultimate quench and quality factor degradation mechanisms

NASA Astrophysics Data System (ADS)

Checchin, Mattia

Superconducting niobium accelerating cavities are devices operating in radiofrequency and able to accelerate charged particles up to energy of tera-electron-volts. Such accelerating structures are though limited in terms of quality factor and accelerating gradient, that translates--in some cases--in higher capital costs of construction and operation of superconducting rf accelerators. Looking forward for a new generation of more affordable accelerators, the physical description of limiting mechanisms in superconducting microwave resonators is discussed. In particular, the physics behind the dissipation introduced by vortices in the superconductor, the ultimate quench limitations and the quality factor degradation mechanism after a quench are described in detail. One of the limiting factor of the quality factor is the dissipation introduced by trapped magnetic flux vortices. The radio-frequency complex response of trapped vortices in superconductors is derived by solving the motion equation for a magnetic flux line, assuming a bi-dimensional and mean free path-dependent Lorentzian-shaped pinning potential. The resulting surface resistance shows the bell-shaped trend as a function of the mean free path, in agreement with the experimental data observed. Such bell-shaped trend of the surface resistance is described in terms of the interplay of the two limiting regimes identified as pinning and flux flow regimes, for low and large mean free path values respectively. The model predicts that the dissipation regime--pinning- or flux-flow-dominated--can be tuned either by acting on the frequency or on the electron mean free path value. The effect of different configurations of pinning sites and strength on the vortex surface resistance are also discussed. Accelerating cavities are also limited by the quench of the superconductive state, which limits the maximum accelerating gradient achievable. The accelerating field limiting factor is usually associated to the superheating field, which is intimately correlated to the penetration of magnetic flux vortices in the material. Experimental data for N-doped cavities suggest that uniform Ginzburg-Landau parameter cavities are statistically limited by the lower critical field, in terms of accelerating gradient. By introducing a Ginzburg-Landau parameter profile at the cavity rf surface--dirty layer--the accelerating gradient of superconducting resonators can be enhanced. The description of the physics behind the accelerating gradient enhancement as a consequence of the dirty layer is carried out by solving numerically the Ginzburg-Landau equations for the layered system. The enhancement is showed to be promoted by the higher energy barrier to vortex penetration, and by the enhanced lower critical field. Another serious threat to the quality factor during the cavity operation is the extra dissipation introduced by the quench. Such quality factor degradation mechanism due to the quench, is generated by the trapping of external magnetic flux at the quench spot. The purely extrinsic origin of such extra dissipation is proven by the impossibility of decrease the quality factor by quenching in a magnetic field-free environment. Also, a clear relation of the dissipation introduced by quenching to the orientation of the applied magnetic field is observed. The full recover of the quality factor by re-quenching in compensated field is possible when the trapped flux at the quench spot is modest. On the contrary, when the trapped magnetic flux is too large, the quality factor degradation may become irreversible by this technique, likely due to the outward flux migration beyond the normal zone opening during the quench.

The lysosomal membrane protein SCAV-3 maintains lysosome integrity and adult longevity

PubMed Central

Li, Yuan; Chen, Baohui; Zou, Wei; Wang, Xin; Wu, Yanwei; Zhao, Dongfeng; Sun, Yanan; Liu, Yubing

2016-01-01

Lysosomes degrade macromolecules and recycle metabolites as well as being involved in diverse processes that regulate cellular homeostasis. The lysosome is limited by a single phospholipid bilayer that forms a barrier to separate the potent luminal hydrolases from other cellular constituents, thus protecting the latter from unwanted degradation. The mechanisms that maintain lysosomal membrane integrity remain unknown. Here, we identified SCAV-3, the Caenorhabditis elegans homologue of human LIMP-2, as a key regulator of lysosome integrity, motility, and dynamics. Loss of scav-3 caused rupture of lysosome membranes and significantly shortened lifespan. Both of these phenotypes were suppressed by reinforced expression of LMP-1 or LMP-2, the C. elegans LAMPs, indicating that longevity requires maintenance of lysosome integrity. Remarkably, reduction in insulin/insulin-like growth factor 1 (IGF-1) signaling suppressed lysosomal damage and extended the lifespan in scav-3(lf) animals in a DAF-16–dependent manner. Our data reveal that SCAV-3 is essential for preserving lysosomal membrane stability and that modulation of lysosome integrity by the insulin/IGF-1 signaling pathway affects longevity. PMID:27810910

Collapse of proteostasis represents an early molecular event in Caenorhabditis elegans aging.

PubMed

Ben-Zvi, Anat; Miller, Elizabeth A; Morimoto, Richard I

2009-09-01

Protein damage contributes prominently to cellular aging. To address whether this occurs at a specific period during aging or accumulates gradually, we monitored the biochemical, cellular, and physiological properties of folding sensors expressed in different tissues of C. elegans. We observed the age-dependent misfolding and loss of function of diverse proteins harboring temperature-sensitive missense mutations in all somatic tissues at the permissive condition. This widespread failure in proteostasis occurs rapidly at an early stage of adulthood, and coincides with a severely reduced activation of the cytoprotective heat shock response and the unfolded protein response. Enhancing stress responsive factors HSF-1 or DAF-16 suppresses misfolding of these metastable folding sensors and restores the ability of the cell to maintain a functional proteome. This suggests that a compromise in the regulation of proteostatic stress responses occurs early in adulthood and tips the balance between the load of damaged proteins and the proteostasis machinery. We propose that the collapse of proteostasis represents an early molecular event of aging that amplifies protein damage in age-associated diseases of protein conformation.

Two Membrane-Associated Tyrosine Phosphatase Homologs Potentiate C. elegans AKT-1/PKB Signaling

PubMed Central

Hu, Patrick J; Xu, Jinling; Ruvkun, Gary

2006-01-01

Akt/protein kinase B (PKB) functions in conserved signaling cascades that regulate growth and metabolism. In humans, Akt/PKB is dysregulated in diabetes and cancer; in Caenorhabditis elegans, Akt/PKB functions in an insulin-like signaling pathway to regulate larval development. To identify molecules that modulate C. elegans Akt/PKB signaling, we performed a genetic screen for enhancers of the akt-1 mutant phenotype (eak). We report the analysis of three eak genes. eak-6 and eak-5/sdf-9 encode protein tyrosine phosphatase homologs; eak-4 encodes a novel protein with an N-myristoylation signal. All three genes are expressed primarily in the two endocrine XXX cells, and their predicted gene products localize to the plasma membrane. Genetic evidence indicates that these proteins function in parallel to AKT-1 to inhibit the FoxO transcription factor DAF-16. These results define two membrane-associated protein tyrosine phosphatase homologs that may potentiate C. elegans Akt/PKB signaling by cell autonomous and cell nonautonomous mechanisms. Similar molecules may modulate Akt/PKB signaling in human endocrine tissues. PMID:16839187

Unconventional Staging Package Selection Leads to Cost Savings

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

,

2012-06-07

In late 2010, U.S. Department of Energy (DOE) Deputy Secretary of Energy, Daniel Poneman, directed that an analysis be conducted on the U-233 steel-clad, Zero Power Reactor (ZPR) fuel plates that were stored at Oak Ridge National Laboratory (ORNL), focusing on cost savings and any potential DOE programmatic needs for the special nuclear material (SNM). The NA-162 Nuclear Criticality Safety Program requested retention of these fuel plates for use in experiments at the Nevada National Security Site (NNSS). A Secretarial Initiative challenged ORNL to make the first shipment to the NNSS by the end of the 2011 calendar year, andmore » this effort became known as the U-233 Project Accelerated Shipping Campaign. To meet the Secretarial Initiative, National Security Technologies, LLC (NSTec), the NNSS Management and Operations contractor, was asked to facilitate the receipt and staging of the U-233 fuel plates in the Device Assembly Facility (DAF). Because there were insufficient staging containers available for the fuel plates, NSTec conducted an analysis of alternatives. The project required a staging method that would reduce the staging footprint while addressing nuclear criticality safety and radiation exposure concerns. To accommodate an intermediate staging method of approximately five years, the NSTec project team determined that a unique and unconventional staging package, the AT-400R, was available to meet the project requirements. By using the AT-400R containers, NSTec was able to realize a cost savings of approximately $10K per container, a total cost savings of nearly $450K.« less

Lipidomic and proteomic analysis of Caenorhabditis elegans lipid droplets and identification of ACS-4 as a lipid droplet-associated protein

DOE PAGES

Vrablik, Tracy L.; Petyuk, Vladislav A.; Larson, Emily M.; ...

2015-06-27

Lipid droplets are cytoplasmic organelles that store neutral lipids for membrane synthesis and energy reserves. In this study, we characterized the lipid and protein composition of purified Caenorhabditis elegans lipid droplets. These lipid droplets are composed mainly of triacylglycerols, surrounded by a phospholipid monolayer composed primarily of phosphatidylcholine and phosphatidylethanolamine. The fatty acid composition of the triacylglycerols is rich in fatty acid species obtained from the dietary Escherichia coli, including cyclopropane fatty acids and cis-vaccenic acid. Unlike other organisms, C. elegans lipid droplets contain very little cholesterol or cholesterol esters. Comparison of the lipid droplet proteomes of wild type andmore » high-fat daf-2 mutant strains shows a very similar proteome in both strains, except that the most abundant protein in the C. elegans lipid droplet proteome, MDT-28, is relatively less abundant in lipid droplets isolated from daf-2 mutants. Functional analysis of lipid droplet proteins identified in our proteomic studies indicated an enrichment of proteins required for growth and fat homeostasis in C. elegans. Finally, we confirmed the localization of one of the newly identified lipid droplet proteins, ACS-4. We found that ACS-4 localizes to the surface of lipid droplets in the C. elegans intestine and skin. This study bolsters C. elegans as a model to study the dynamics and functions of lipid droplets in a multicellular organism.« less

Synthesis, spectroscopic, coordination and biological activities of some organometallic complexes derived from thio-Schiff base ligands

NASA Astrophysics Data System (ADS)

Abou-Hussein, Azza A.; Linert, Wolfgang

2014-01-01

Two series of mono- and binuclear complexes cyclic or acyclic thio-ferocine Schiff base ligands, derived from the condensation of 2-aminobenzenthiol (L) with monoacetyl ferrocene in the molar ratio 1:1 or in the molar ratio 1:2 for diacetyl ferocine have been prepared. The condensation reactions yield the corresponding Schiff Base ligands, HLa-Maf and H2Lb-Daf. The chelation of the ligands to metal ions occurs through the sulfur of the thiol group as well as the nitrogen atoms of the azomethine group of the ligands. HLa-Maf acts as monobasic bidentate or dibasic tetradentate, while H2Lb-Daf behaves as twice negatively cargend tetradentate ligand. The structures of these ligands were elucidated by elemental analysis, infrared, ultraviolet-visible spectra, as well as 1H NMR spectra. Reactions of the Schiff bases ligands with ruthenium(III), oxovanadium(IV) and dioxouranium(VI) afforded the corresponding transition metal complexes. The properties of the newly prepared complexes were analyse by elemental analyses, infrared, electronic spectra, 1H NMR as well as the magnetic susceptibility and conductivity measurement. The metal complexes exhibits different geometrical arrangements such as octahedral and square pyramidal coordination. Schiff base ligands and their metal complexes were tested against two pathogenic bacteria as Gram-positive and Gram-negative bacteria as well as one kind of fungi to study their biological activity. All the complexes exhibit antibacterial and antifungal activities against these organisms.

Phenotyping of congenic dipeptidyl peptidase 4 (DP4) deficient Dark Agouti (DA) rats suggests involvement of DP4 in neuro-, endocrine, and immune functions.

PubMed

Frerker, Nadine; Raber, Kerstin; Bode, Felix; Skripuletz, Thomas; Nave, Heike; Klemann, Christian; Pabst, Reinhard; Stephan, Michael; Schade, Jutta; Brabant, Georg; Wedekind, Dirk; Jacobs, Roland; Jörns, Anne; Forssmann, Ulf; Straub, Rainer H; Johannes, Sigrid; Hoffmann, Torsten; Wagner, Leona; Demuth, Hans-Ulrich; von Hörsten, Stephan

2009-01-01

Treatment of diabetes type 2 using chronic pharmacological inhibition of dipeptidyl peptidase 4 (DP4) still requires an in-depth analysis of models for chronic DP4 deficiency, because adverse reactions induced by some DP4 inhibitors have been described. In the present study, a novel congenic rat model of DP4 deficiency on a "DP4-high" DA rat genetic background was generated (DA.F344-Dpp4(m)/ SvH rats) and comprehensively phenotyped. Similar to chronic pharmacological inhibition of DP4, DP4 deficient rats exhibited a phenotype involving reduced diet-induced body weight gain and improved glucose tolerance associated with increased levels of glucagon-like peptide-1 (GLP-1) and bound leptin as well as decreased aminotransferases and triglycerides. Additionally, DA.F344-Dpp4(m)/SvH rats showed anxiolytic-like and reduced stress-like responses, a phenomenon presently not targeted by DP4 inhibitors. However, several immune alterations, such as differential leukocyte subset composition at baseline, blunted natural killer cell and T-cell functions, and altered cytokine levels were observed. While this animal model confirms a critical role of DP4 in GLP-1-dependent glucose regulation, genetically induced chronic DP4 deficiency apparently also affects stress-regulatory and immuneregulatory systems, indicating that the use of chronic DP4 inhibitors might have the potential to interfere with central nervous system and immune functions in vivo.

Pretreatment of bakery wastewater by coagulation-flocculation and dissolved air flotation.

PubMed

Liu, J C; Lien, C S

2001-01-01

The pretreatment of wastewater from a large-scale bakery was studied. In the coagulation-flocculation reaction, it was found that both alum and FeCl3 were effective in the jar tests. When at coagulant dosage of 90 to 100 mg/l, 55% of COD and 95 to 100% of SS could be removed. The optimum pH was at 6.0. In addition, the removal of SS was affected by pH more significantly, while the removal of COD was not affected in the pH range of 6.0 to 8.0. In the DAF experiments, 48.6% of COD and 69.8% of SS were removed in 10 min at a pressure of 4 kg/cm2, recycle ratio of 0.3 l/min, and pH of 6.0. Upon the addition of 100 mg/l of alum, the removal efficiency of COD did not increase while SS removal increased to 82.1%. It was found that 5-min flocculation time did improve the COD removal while it had little effect on SS removal. Flocculation for longer than 5 min did not enhance the flotation performance. Similar phenomena were observed when FeCl3 was used as the coagulant, except that flocculation had an insignificant effect on COD and SS removal. It was also found that FeCl3 was relatively more effective than alum. In summary, both coagulation-flocculation and DAF were efficient for the pretreatment. The advantages and disadvantages were discussed.

Zinc Levels Modulate Lifespan through Multiple Longevity Pathways in Caenorhabditis elegans

PubMed Central

Kumar, Jitendra; Barhydt, Tracy; Awasthi, Anjali; Lithgow, Gordon J.; Killilea, David W.; Kapahi, Pankaj

2016-01-01

Zinc is an essential trace metal that has integral roles in numerous biological processes, including enzymatic function, protein structure, and cell signaling pathways. Both excess and deficiency of zinc can lead to detrimental effects on development and metabolism, resulting in abnormalities and disease. We altered the zinc balance within Caenorhabditis elegans to examine how changes in zinc burden affect longevity and healthspan in an invertebrate animal model. We found that increasing zinc levels in vivo with excess dietary zinc supplementation decreased the mean and maximum lifespan, whereas reducing zinc levels in vivo with a zinc-selective chelator increased the mean and maximum lifespan in C. elegans. We determined that the lifespan shortening effects of excess zinc required expression of DAF-16, HSF-1 and SKN-1 proteins, whereas the lifespan lengthening effects of the reduced zinc may be partially dependent upon this set of proteins. Furthermore, reducing zinc levels led to greater nuclear localization of DAF-16 and enhanced dauer formation compared to controls, suggesting that the lifespan effects of zinc are mediated in part by the insulin/IGF-1 pathway. Additionally, zinc status correlated with several markers of healthspan in worms, including proteostasis, locomotion and thermotolerance, with reduced zinc levels always associated with improvements in function. Taken together, these data support a role for zinc in regulating both development and lifespan in C. elegans, and that suggest that regulation of zinc homeostasis in the worm may be an example of antagonistic pleiotropy. PMID:27078872

Shielding evaluation for IMRT implementation in an existing accelerator vault

PubMed Central

Price, R. A.; Chibani, O.; Ma, C.‐M.

2003-01-01

A formalism is developed for evaluating the shielding in an existing vault to be used for IMRT. Existing exposure rate measurements are utilized as well as a newly developed effective modulation scaling factor. Examples are given for vaults housing 6, 10 and 18 MV linear accelerators. The use of an 18 MV Siemens linear accelerator is evaluated for IMRT delivery with respect to neutron production and the effects on individual patients. A modified modulation scaling factor is developed and the risk of the incurrence of fatal secondary malignancies is estimated. The difference in neutron production between 18 MV Varian and Siemens accelerators is estimated using Monte Carlo results. The neutron production from the Siemens accelerator is found to be approximately 4 times less than that of the Varian accelerator resulting in a risk of fatal secondary malignancy occurrence of approximately 1.6% when using the SMLC delivery technique and our measured modulation scaling factors. This compares with a previously published value of 1.6% for routine 3D CRT delivery on the Varian accelerator. PACS number(s): 87.52.Ga, 87.52.Px, 87.53.Qc, 87.53.Wz PMID:12841794

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

Checchin, Mattia

Superconducting niobium accelerating cavities are devices operating in radio-frequency and able to accelerate charged particles up to energy of tera-electron-volts. Such accelerating structures are though limited in terms of quality factor and accelerating gradient, that translates--in some cases--in higher capital costs of construction and operation of superconducting rf accelerators. Looking forward for a new generation of more affordable accelerators, the physical description of limiting mechanisms in superconducting microwave resonators is discussed. In particular, the physics behind the dissipation introduced by vortices in the superconductor, the ultimate quench limitations and the quality factor degradation mechanism after a quench are described inmore » detail. One of the limiting factor of the quality factor is the dissipation introduced by trapped magnetic flux vortices. The radio-frequency complex response of trapped vortices in superconductors is derived by solving the motion equation for a magnetic flux line, assuming a bi-dimensional and mean free path-dependent Lorentzian-shaped pinning potential. The resulting surface resistance shows the bell-shaped trend as a function of the mean free path, in agreement with the experimental data observed. Such bell-shaped trend of the surface resistance is described in terms of the interplay of the two limiting regimes identified as pinning and flux flow regimes, for low and large mean free path values respectively. The model predicts that the dissipation regime--pinning- or flux-flow-dominated--can be tuned either by acting on the frequency or on the electron mean free path value. The effect of different configurations of pinning sites and strength on the vortex surface resistance are also discussed. Accelerating cavities are also limited by the quench of the superconductive state, which limits the maximum accelerating gradient achievable. The accelerating field limiting factor is usually associate d to the superheating field, which is intimately correlated to the penetration of magnetic flux vortices in the material. Experimental data for N-doped cavities suggest that uniform Ginzburg-Landau parameter cavities are statistically limited by the lower critical field, in terms of accelerating gradient. By introducing a Ginzburg-Landau parameter profile at the cavity rf surface--dirty layer--the accelerating gradient of superconducting resonators can be enhanced. The description of the physics behind the accelerating gradient enhancement as a consequence of the dirty layer is carried out by solving numerically the Ginzburg-Landau equations for the layered system. The enhancement is showed to be promoted by the higher energy barrier to vortex penetration, and by the enhanced lower critical field. Another serious threat to the quality factor during the cavity operation is the extra dissipation introduced by the quench. Such quality factor degradation mechanism due to the quench, is generated by the trapping of external magnetic flux at quench spot. The purely extrinsic origin of such extra dissipation is proven by the impossibility of decrease the quality factor by quenching in a magnetic field-free environment. Also, a clear relation of the dissipation introduced by quenching to the orientation of the applied magnetic field is observed. The full recover of the quality factor by re-quenching in compensated field is possible when the trapped flux at the quench spot is modest. On the contrary, when the trapped magnetic flux is too large, the quality factor degradation may become irreversible by this technique, likely due to the outward flux migration beyond the normal zone opening during the quench.« less

Geologic history of the polar regions of Mars based on Mars Global survey data. I. Noachian and Hesperian Periods

USGS Publications Warehouse

Tanaka, K.L.; Kolb, E.J.

2001-01-01

During the Noachian Period, the south polar region of Mars underwent intense cratering, construction of three groups of volcanoes, widespread contractional deformation, resurfacing of low areas, and local dissection of valley networks; no evidence for polar deposits, ice sheets, or glaciation is recognized. South polar Hesperian geology is broadly characterized by waning impacts, volcanism, and tectonism. Emplacement of the polar Dorsa Argentea Formation (DAF) occurred during the Hesperian Period. Mars Orbiter Laser Altimeter topographic data and Mars Orbiter Camera images elucidate stratigraphic, morphologic, and topographic relations, permitting the dividing of the DAF into eight members, which surround and underlie about half of the Amazonian south polar layered deposits. The lobate fronts and lack of typical volcanic-flow morphology of the six plains units indicate that they may be made up of debris flows. We think that these flows, tens of meters to 200 m thick, may have originated by the discharge of huge volumes of slurry fluidized by ground water or liquid CO2, perhaps triggered by local impacts, igneous activity, or basal melting beneath polar deposits. The cavi and rugged members include irregular depressions that penetrate the subsurface; some of the pits have raised rims. The depressions may have formed by collapse due to expulsion of subsurface material in which local explosive activity built up the raised rims. Further, smaller eruptions of volatile-rich material may have resulted in narrow, sinuous channel deposits within aggrading fine-grained unconsolidated material perhaps produced by gaseous discharge of subsurface volatiles; preferential erosion of the latter material could have produced the Dorsa Argentea-type ginuous ridges associated mainly with the DAF. Alternatively, the ridges may be eskers, but the lack of associated glacial and fluvial morphologies casts doubt on this interpretation. The knobby, degraded materials forming Scandia Colles may represent the only Noachian geologic record exposed in the north polar region. Most of the north polar region was buried by water- or debris-ocean sediments during the Hesperian Period, originating from uplands areas and perhaps knobby terrains in the northern plains. The sediments either mantle or were deformed by wrinkle ridges radial and concentric to Utopia basin and concentric to northern Tharsis. Sources of stress probably included sediment loading in the northern plains and regional magmatic and loading activity at Tharsis. Polar layered deposits began piling up during the Early Amazonian or later. ?? 2001 Elsevier Science.

Geologic History of the Polar Regions of Mars Based on Mars Global Surveyor Data. I. Noachian and Hesperian Periods

NASA Astrophysics Data System (ADS)

Tanaka, Kenneth L.; Kolb, Eric J.

2001-11-01

During the Noachian Period, the south polar region of Mars underwent intense cratering, construction of three groups of volcanoes, widespread contractional deformation, resurfacing of low areas, and local dissection of valley networks; no evidence for polar deposits, ice sheets, or glaciation is recognized. South polar Hesperian geology is broadly characterized by waning impacts, volcanism, and tectonism. Emplacement of the polar Dorsa Argentea Formation (DAF) occurred during the Hesperian Period. Mars Orbiter Laser Altimeter topographic data and Mars Orbiter Camera images elucidate stratigraphic, morphologic, and topographic relations, permitting the dividing of the DAF into eight members, which surround and underlie about half of the Amazonian south polar layered deposits. The lobate fronts and lack of typical volcanic-flow morphology of the six plains units indicate that they may be made up of debris flows. We think that these flows, tens of meters to 200 m thick, may have originated by the discharge of huge volumes of slurry fluidized by ground water or liquid CO 2, perhaps triggered by local impacts, igneous activity, or basal melting beneath polar deposits. The cavi and rugged members include irregular depressions that penetrate the subsurface; some of the pits have raised rims. The depressions may have formed by collapse due to expulsion of subsurface material in which local explosive activity built up the raised rims. Further, smaller eruptions of volatile-rich material may have resulted in narrow, sinuous channel deposits within aggrading fine-grained unconsolidated material perhaps produced by gaseous discharge of subsurface volatiles; preferential erosion of the latter material could have produced the Dorsa Argentea-type sinuous ridges associated mainly with the DAF. Alternatively, the ridges may be eskers, but the lack of associated glacial and fluvial morphologies casts doubt on this interpretation. The knobby, degraded materials forming Scandia Colles may represent the only Noachian geologic record exposed in the north polar region. Most of the north polar region was buried by water- or debris-ocean sediments during the Hesperian Period, originating from uplands areas and perhaps knobby terrains in the northern plains. The sediments either mantle or were deformed by wrinkle ridges radial and concentric to Utopia basin and concentric to northern Tharsis. Sources of stress probably included sediment loading in the northern plains and regional magmatic and loading activity at Tharsis. Polar layered deposits began piling up during the Early Amazonian or later.

SU-F-T-66: Characteristics of Electron Beams From Varian Trubeam

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

Dimofte, A; Kennedy, C; Zhu, T

2016-06-15

Purpose: The purpose of this study was to compare the electron beam data between Truebeam and 2300ix Varian accelerators for percent depth dose for broad beam and small circular cutouts, cone factors, head scatter factor as a function of cone size and SSD, phantom scatter factor, blocking factor, distance factor and virtual source position. Methods: Measurements were performed for Truebeam and 2300ix Varian accelerators. The main energies used were: 6, 9, 12, 16 and 20 MeV. PDD was measured at SSD = 100 cm for open beam and small circular cutouts (r = 0.5, 1.0, 1.5, 2.0, 3.0, 4.0 andmore » 6.6cm) for different energies. Measurements to determine the head scatter factor (H) were done as a function of radius for six representative energies and five cone sizes (6, 10, 15, 20 and 25cm2). The phantom scatter factor (PSF) is defined as the ratio of blocking factor in water at reference depth and head scatter factor in air. PSF was measured as a function of radius and electron energy. Distance factor was measured for all energies and cones for three SSD’s (100, 110 and 120cm). Results: The percent depth dose (PDD) was measured for small cutouts of radius r = 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0 and 5.6cm. Blocking factor (BF) was measured for Truebeam and 2300ix accelerators, for different circular cutouts and energies for a 10×10 cone. Cone factors were compared between the two accelerators for different energies and applicator sizes. Conclusion: Cone factors measured for the two accelerator types differ by up to 5% for the largest applicator size. Blocking factors differs by up to 3%, with the largest variation for the smallest field size (0.5cm). Distance factor for different SSD’s differ by up to 4.5%.« less

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

NASA Technical Reports Server (NTRS)

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.

SMART empirical approaches for predicting field performance of PV modules from results of reliability tests

NASA Astrophysics Data System (ADS)

Hardikar, Kedar Y.; Liu, Bill J. J.; Bheemreddy, Venkata

2016-09-01

Gaining an understanding of degradation mechanisms and their characterization are critical in developing relevant accelerated tests to ensure PV module performance warranty over a typical lifetime of 25 years. As newer technologies are adapted for PV, including new PV cell technologies, new packaging materials, and newer product designs, the availability of field data over extended periods of time for product performance assessment cannot be expected within the typical timeframe for business decisions. In this work, to enable product design decisions and product performance assessment for PV modules utilizing newer technologies, Simulation and Mechanism based Accelerated Reliability Testing (SMART) methodology and empirical approaches to predict field performance from accelerated test results are presented. The method is demonstrated for field life assessment of flexible PV modules based on degradation mechanisms observed in two accelerated tests, namely, Damp Heat and Thermal Cycling. The method is based on design of accelerated testing scheme with the intent to develop relevant acceleration factor models. The acceleration factor model is validated by extensive reliability testing under different conditions going beyond the established certification standards. Once the acceleration factor model is validated for the test matrix a modeling scheme is developed to predict field performance from results of accelerated testing for particular failure modes of interest. Further refinement of the model can continue as more field data becomes available. While the demonstration of the method in this work is for thin film flexible PV modules, the framework and methodology can be adapted to other PV products.

Histologic Changes Caused by Application of Lewisite Analogs to Mouse Skin and Human Skin Xenografts

DTIC Science & Technology

1985-01-01

CLASSIICATION OF THIS PAGE (Nh..1 DO&a Eatat1d UNCLAS8inED S6CURmTV CLASSISCATION OP THIS PA•r(em Daf EMo* skin grafts : 1) epidermal cellular nuclear...microscopy. Under light microscopy, we observed the following changes In PDA-treated human skin grafts : I) epidermal cellular nuclear degeneration (apparent...needed. (Oe such model is ti-e human skin grafted athymic nude mouse (4,5). This animal model was recently established at LAIR. PhenyLdichLoroarsine (PDA

Highly Polluted Wastewaters Treatment by Improved Dissolved Air Flotation Technology

NASA Astrophysics Data System (ADS)

Moga, I. C.; Covaliu, C. I.; Matache, M. G.; Doroftei, B. I.

2017-06-01

Numerous investigations are oriented towards the development of new wastewater treatment technologies, having high efficiencies for removing even low concentrations of pollutants found in water. These efforts were determined by the destroyer impact of the pollutants to the environment and human’s health. For this reason this paper presents our study concerning an improved dissolved air flotation technology for wastewater treatment. There is described a dissolved air flotation (DAF) installation composed by two equipments: pressurized capsule and lamellar settling. Also, there are presented some advantages of using nanoparticles as flotation collectors.

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

Heinrichs, Dave; Beller, Tim; Burch, Jennifer

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.

The answer is questions: accelerated-nursing students report practice questions are fundamental to first-time NCLEX-RN success.

PubMed

Blozen, Barbara B

2014-01-01

There are a number of anecdotal reports on demographic characteristics and academic success of accelerated-nursing students; yet few empirical studies have examined accelerated-nursing students NCLEX-RN success. Applying Knowles' adult learning theory as a guiding framework, the purpose of this qualitative study was to explore, from the accelerated-nursing students' perspective, the factors reported as contributing to their success on the NCLEX-RN. The research questions aimed to elicit participants' descriptions of their experiences and factors contributing to their success via individual interviews. The most significant finding the participants identified as the factor that contributed to their success was the practicing of NCLEX-RN questions. The findings of this study have several implications for educational policy and practice for universities and schools of nursing as the information gained from this study applies to recruitment and retention as well as curriculum and educational strategies in an accelerated-nursing program.

Superconducting traveling wave accelerators

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

Farkas, Z.D.

1984-11-01

This note considers the applicability of superconductivity to traveling wave accelerators. Unlike CW operation of a superconducting standing wave or circulating wave accelerator section, which requires improvement factors (superconductor conductivity divided by copper conductivity) of about 10/sup 6/ in order to be of practical use, a SUperconducting TRaveling wave Accelerator, SUTRA, operating in the pulsed mode requires improvement factors as low as about 10/sup 3/, which are attainable with niobium or lead at 4.2K, the temperature of liquid helium at atmospheric pressure. Changing from a copper traveling wave accelerator to SUTRA achieves the following. (1) For a given gradient SUTRAmore » reduces the peak and average power requirements typically by a factor of 2. (2) SUTRA reduces the peak power still further because it enables us to increase the filling time and thus trade pulse width for gradient. (3) SUTRA makes possible a reasonably long section at higher frequencies. (4) SUTRA makes possible recirculation without additional rf average power. 8 references, 6 figures, 1 table.« less

Regulation of cuticle formation during fruit development and ripening in 'Newhall' navel orange (Citrus sinensis Osbeck) revealed by transcriptomic and metabolomic profiling.

PubMed

Wang, Jinqiu; Sun, Li; Xie, Li; He, Yizhong; Luo, Tao; Sheng, Ling; Luo, Yi; Zeng, Yunliu; Xu, Juan; Deng, Xiuxin; Cheng, Yunjiang

2016-02-01

Fruit cuticle, which is composed of cutin and wax and biosynthesized during fruit development, plays important roles in the prevention of water loss and the resistance to pathogen infection during fruit development and postharvest storage. However, the key factors and mechanisms regarding the cuticle biosynthesis in citrus fruits are still unclear. Here, fruit cuticle of 'Newhall' navel orange (Citrus sinensis Osbeck) was studied from the stage of fruit expansion to postharvest storage from the perspectives of morphology, transcription and metabolism. The results demonstrated that cutin accumulation is synchronous with fruit expansion, while wax synthesis is synchronous with fruit maturation. Metabolic profile of fruits peel revealed that transition of metabolism of fruit peel occurred from 120 to 150 DAF and ABA was predicted to regulate citrus wax synthesis during the development of Newhall fruits. RNA-seq analysis of the peel from the above two stages manifested that the genes involved in photosynthesis were repressed, while the genes involved in the biosynthesis of wax, cutin and lignin were significantly induced at later stages. Further real-time PCR predicted that MYB transcription factor GL1-like regulates citrus fruits wax synthesis. These results are valuable for improving the fruit quality during development and storage. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Multilevel acceleration of scattering-source iterations with application to electron transport

DOE PAGES

Drumm, Clif; Fan, Wesley

2017-08-18

Acceleration/preconditioning strategies available in the SCEPTRE radiation transport code are described. A flexible transport synthetic acceleration (TSA) algorithm that uses a low-order discrete-ordinates (S N) or spherical-harmonics (P N) solve to accelerate convergence of a high-order S N source-iteration (SI) solve is described. Convergence of the low-order solves can be further accelerated by applying off-the-shelf incomplete-factorization or algebraic-multigrid methods. Also available is an algorithm that uses a generalized minimum residual (GMRES) iterative method rather than SI for convergence, using a parallel sweep-based solver to build up a Krylov subspace. TSA has been applied as a preconditioner to accelerate the convergencemore » of the GMRES iterations. The methods are applied to several problems involving electron transport and problems with artificial cross sections with large scattering ratios. These methods were compared and evaluated by considering material discontinuities and scattering anisotropy. Observed accelerations obtained are highly problem dependent, but speedup factors around 10 have been observed in typical applications.« less

OARE flight maneuvers and calibration measurements on STS-58

NASA Technical Reports Server (NTRS)

Blanchard, Robert C.; Nicholson, John Y.; Ritter, James R.; Larman, Kevin T.

1994-01-01

The Orbital Acceleration Research Experiment (OARE), which has flown on STS-40, STS-50, and STS-58, contains a three axis accelerometer with a single, nonpendulous, electrostatically suspended proofmass which can resolve accelerations to the nano-g level. The experiment also contains a full calibration station to permit in situ bias and scale factor calibration. This on-orbit calibration capability eliminates the large uncertainty of ground-based calibrations encountered with accelerometers flown in the past on the orbiter, thus providing absolute acceleration measurement accuracy heretofore unachievable. This is the first time accelerometer scale factor measurements have been performed on orbit. A detailed analysis of the calibration process is given along with results of the calibration factors from the on-orbit OARE flight measurements on STS-58. In addition, the analysis of OARE flight maneuver data used to validate the scale factor measurements in the sensor's most sensitive range is also presented. Estimates on calibration uncertainties are discussed. This provides bounds on the STS-58 absolute acceleration measurements for future applications.

d-Allulose, a stereoisomer of d-fructose, extends Caenorhabditis elegans lifespan through a dietary restriction mechanism: A new candidate dietary restriction mimetic.

PubMed

Shintani, Tomoya; Sakoguchi, Hirofumi; Yoshihara, Akihide; Izumori, Ken; Sato, Masashi

2017-12-02

Dietary restriction (DR) is an effective intervention known to increase lifespan in a wide variety of organisms. DR also delays the onset of aging-associated diseases. DR mimetics, compounds that can mimic the effects of DR, have been intensively explored. d-Allulose (d-Alu), the C3-epimer of d-fructose, is a rare sugar that has various health benefits, including anti-hyperglycemia and anti-obesity effects. Here, we report that d-Alu increased the lifespan of Caenorhabditis elegans both under monoxenic and axenic culture conditions. d-Alu did not further extend the lifespan of the long-lived DR model eat-2 mutant, strongly indicating that the effect is related to DR. However, d-Alu did not reduce the food intake of wild-type C. elegans. To explore the mechanisms of the d-Alu longevity effect, we examined the lifespan of d-Alu-treated mutants deficient for nutrient sensing pathway-related genes daf-16, sir-2.1, aak-2, and skn-1. As a result, d-Alu increased the lifespan of the daf-16, sir-2.1, and skn-1 mutants, but not the aak-2 mutant, indicating that the lifespan extension was dependent on the energy sensor, AMP-activated protein kinase (AMPK). d-Alu also enhanced the mRNA expression and enzyme activities of superoxide dismutase (SOD) and catalase. From these findings, we conclude that d-Alu extends lifespan by increasing oxidative stress resistance through a DR mechanism, making it a candidate DR mimetic. Copyright © 2017 Elsevier Inc. All rights reserved.

Nematode orphan genes are adopted by conserved regulatory networks and find a home in ecology.

PubMed

Mayer, Melanie G; Sommer, Ralf J

2015-01-01

Nematode dauer formation represents an essential survival and dispersal strategy and is one of a few ecologically relevant traits that can be studied in laboratory approaches. Under harsh environmental conditions, the nematode model organisms Caenorhabditis elegans and Pristionchus pacificus arrest their development and induce the formation of stress-resistant dauer larvae in response to dauer pheromones, representing a key example of phenotypic plasticity. Previous studies have indicated that in P. pacificus, many wild isolates show cross-preference of dauer pheromones and compete for access to a limited food source. When investigating the genetic mechanisms underlying this intraspecific competition, we recently discovered that the orphan gene dauerless (dau-1) controls dauer formation by copy number variation. Our results show that dau-1 acts in parallel to or downstream of steroid hormone signaling but upstream of the nuclear hormone receptor daf-12, suggesting that DAU-1 represents a novel inhibitor of DAF-12. Phylogenetic analysis reveals that the observed copy number variation is part of a complex series of gene duplication events that occurred over short evolutionary time scales. Here, we comment on the incorporation of novel or fast-evolving genes into conserved genetic networks as a common principle for the evolution of phenotypic plasticity and intraspecific competition. We discuss the possibility that orphan genes might often function in the regulation and execution of ecologically relevant traits. Given that only few ecological processes can be studied in model organisms, the function of such genes might often go unnoticed, explaining the large number of uncharacterized genes in model system genomes.

A pilot randomized controlled trial of the Occupational Goal Intervention method for the improvement of executive functioning in patients with treatment-resistant schizophrenia.

PubMed

Vizzotto, Adriana D B; Celestino, Diego L; Buchain, Patricia C; Oliveira, Alexandra M; Oliveira, Graça M R; Di Sarno, Elaine S; Napolitano, Isabel C; Elkis, Helio

2016-11-30

Schizophrenia is a chronic disabling mental disorder that involves impairments in several cognitive domains, especially in executive functions (EF), as well as impairments in functional performance. This is particularly true in patients with Treatment-Resistant Schizophrenia (TRS). The aim of this study was to test the efficacy of the Occupational Goal Intervention (OGI) method for the improvement of EF in patients with TRS. In this randomized, controlled, single-blind pilot study, 25 TRS patients were randomly assigned to attend 30 sessions of either OGI or craft activities (control) over a 15-week period and evaluated by the Behavioural Assessment of the Dysexecutive Syndrome (BADS) as the primary outcome and the Direct Assessment of Functional Status (DAFS-BR) as well as the Independent Living Skills Survey (ILSS-BR) as secondary outcomes, all adapted for the Brazilian population. The Positive and Negative Syndrome Scale (PANSS) was used for monitoring symptom severity. Results showed significant statistical differences, favoring the OGI group in terms of improvement on the BADS, both in subtests (Action Program and Key Search) and the total score. Improvements in EFs were observed by families in various dimensions as measured by different subtests of the ILSS-BR inventory. The OGI group showed no significant results in secondary outcomes (DAFS-BR) except in terms of improvement of communication skills. Although preliminary, our results indicate that the OGI method is efficacious and effective for patients with TRS. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Diversity among Cynodon accessions and taxa based on DNA amplification fingerprinting.

PubMed

Assefa, S; Taliaferro, C M; Anderson, M P; de los Reyes, B G; Edwards, R M

1999-06-01

The genus Cynodon (Gramineae), comprised of 9 species, is geographically widely distributed and genetically diverse. Information on the amounts of molecular genetic variation among and within Cynodon taxa is needed to enhance understanding of phylogenetic relations and facilitate germplasm management and breeding improvement efforts. Genetic relatedness among 62 Cynodon accessions, representing eight species, was assessed using DNA amplification fingerprinting (DAF). Ten 8-mer oligonucleotides were used to amplify specific Cynodon genomic sequences. The DNA amplification products of individual accessions were scored for presence (1) or absence (0) of bands. Similarity matrices were developed and the accessions were grouped by cluster (UPGMA) and principal coordinate analysis. Analyses were conducted within ploidy level (2x = 18 and 4x = 36) and over ploidy levels. Each primer revealed polymorphic loci among accessions within species. Of 539 loci (bands) scored, 496 (92%) were polymorphic. Cynodon arcuatus was clearly separated from other species by numerous monomorphic bands. The strongest species similarities were between C. aethiopicus and C. arcuatus, C. transvaalensis and C. plectostachyus, and C. incompletus and C. nlemfuensis. Intraspecific variation was least for C. aethiopicus, C. arcuatus, and C. transvaalensis, and greatest for C. dactylon. Accessions of like taxonomic classification were generally clustered, except the cosmopolitan C. dactylon var. dactylon and C. dactylon var. afganicus. Within taxa, accessions differing in chromosome number clustered in all instances indicating the 2x and 4x forms to be closely related. Little, if any, relationship was found between relatedness as indicated by the DAF profiles and previous estimates of hybridization potential between the different taxa.

Does electromagnetic radiation accelerate galactic cosmic rays

NASA Technical Reports Server (NTRS)

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.

An accelerated subspace iteration for eigenvector derivatives

NASA Technical Reports Server (NTRS)

Ting, Tienko

1991-01-01

An accelerated subspace iteration method for calculating eigenvector derivatives has been developed. Factors affecting the effectiveness and the reliability of the subspace iteration are identified, and effective strategies concerning these factors are presented. The method has been implemented, and the results of a demonstration problem are presented.

Solution of elliptic partial differential equations by fast Poisson solvers using a local relaxation factor. 2: Two-step method

NASA Technical Reports Server (NTRS)

Chang, S. C.

1986-01-01

A two-step semidirect procedure is developed to accelerate the one-step procedure described in NASA TP-2529. For a set of constant coefficient model problems, the acceleration factor increases from 1 to 2 as the one-step procedure convergence rate decreases from + infinity to 0. It is also shown numerically that the two-step procedure can substantially accelerate the convergence of the numerical solution of many partial differential equations (PDE's) with variable coefficients.

Study on Misalignment Angle Compensation during Scale Factor Matching for Two Pairs of Accelerometers in a Gravity Gradient Instrument

PubMed Central

Huang, Xiangqing; Deng, Zhongguang; Xie, Yafei; Fan, Ji; Hu, Chenyuan

2018-01-01

A method for automatic compensation of misalignment angles during matching the scale factors of two pairs of the accelerometers in developing the rotating accelerometer gravity gradient instrument (GGI) is proposed and demonstrated in this paper. The purpose of automatic scale factor matching of the four accelerometers in GGI is to suppress the common mode acceleration of the moving-based platforms. However, taking the full model equation of the accelerometer into consideration, the other two orthogonal axes which is the pendulous axis and the output axis, will also sense the common mode acceleration and reduce the suppression performance. The coefficients from the two axes to the output are δO and δP respectively, called the misalignment angles. The angle δO, coupling with the acceleration along the pendulous axis perpendicular to the rotational plane, will not be modulated by the rotation and gives little contribution to the scale factors matching. On the other hand, because of coupling with the acceleration along the centripetal direction in the rotating plane, the angle δP would produce a component with 90 degrees phase delay relative to the scale factor component. Hence, the δP component coincides exactly with the sensitive direction of the orthogonal accelerometers. To improve the common mode acceleration rejection, the misalignment angle δP is compensated by injecting a trimming current, which is proportional to the output of an orthogonal accelerometer, into the torque coil of the accelerometer during the scale factor matching. The experimental results show that the common linear acceleration suppression achieved three orders after the scale factors balance and five orders after the misalignment angles compensation, which is almost down to the noise level of the used accelerometers of 1~2 × 10−7 g/√Hz (1 g ≈ 9.8 m/s2). PMID:29670021

Study on Misalignment Angle Compensation during Scale Factor Matching for Two Pairs of Accelerometers in a Gravity Gradient Instrument.

PubMed

Huang, Xiangqing; Deng, Zhongguang; Xie, Yafei; Fan, Ji; Hu, Chenyuan; Tu, Liangcheng

2018-04-18

A method for automatic compensation of misalignment angles during matching the scale factors of two pairs of the accelerometers in developing the rotating accelerometer gravity gradient instrument (GGI) is proposed and demonstrated in this paper. The purpose of automatic scale factor matching of the four accelerometers in GGI is to suppress the common mode acceleration of the moving-based platforms. However, taking the full model equation of the accelerometer into consideration, the other two orthogonal axes which is the pendulous axis and the output axis, will also sense the common mode acceleration and reduce the suppression performance. The coefficients from the two axes to the output are δ O and δ P respectively, called the misalignment angles. The angle δ O , coupling with the acceleration along the pendulous axis perpendicular to the rotational plane, will not be modulated by the rotation and gives little contribution to the scale factors matching. On the other hand, because of coupling with the acceleration along the centripetal direction in the rotating plane, the angle δ P would produce a component with 90 degrees phase delay relative to the scale factor component. Hence, the δ P component coincides exactly with the sensitive direction of the orthogonal accelerometers. To improve the common mode acceleration rejection, the misalignment angle δ P is compensated by injecting a trimming current, which is proportional to the output of an orthogonal accelerometer, into the torque coil of the accelerometer during the scale factor matching. The experimental results show that the common linear acceleration suppression achieved three orders after the scale factors balance and five orders after the misalignment angles compensation, which is almost down to the noise level of the used accelerometers of 1~2 × 10 −7 g/√Hz (1 g ≈ 9.8 m/s²).

Analysis of Weibull Grading Test for Solid Tantalum Capacitors

NASA Technical Reports Server (NTRS)

Teverovsky, Alexander

2010-01-01

Weibull grading test is a powerful technique that allows selection and reliability rating of solid tantalum capacitors for military and space applications. However, inaccuracies in the existing method and non-adequate acceleration factors can result in significant, up to three orders of magnitude, errors in the calculated failure rate of capacitors. This paper analyzes deficiencies of the existing technique and recommends more accurate method of calculations. A physical model presenting failures of tantalum capacitors as time-dependent-dielectric-breakdown is used to determine voltage and temperature acceleration factors and select adequate Weibull grading test conditions. This, model is verified by highly accelerated life testing (HALT) at different temperature and voltage conditions for three types of solid chip tantalum capacitors. It is shown that parameters of the model and acceleration factors can be calculated using a general log-linear relationship for the characteristic life with two stress levels.

Reliability of High-Voltage Tantalum Capacitors. Parts 3 and 4)

NASA Technical Reports Server (NTRS)

Teverovsky, Alexander

2010-01-01

Weibull grading test is a powerful technique that allows selection and reliability rating of solid tantalum capacitors for military and space applications. However, inaccuracies in the existing method and non-adequate acceleration factors can result in significant, up to three orders of magnitude, errors in the calculated failure rate of capacitors. This paper analyzes deficiencies of the existing technique and recommends more accurate method of calculations. A physical model presenting failures of tantalum capacitors as time-dependent-dielectric-breakdown is used to determine voltage and temperature acceleration factors and select adequate Weibull grading test conditions. This model is verified by highly accelerated life testing (HALT) at different temperature and voltage conditions for three types of solid chip tantalum capacitors. It is shown that parameters of the model and acceleration factors can be calculated using a general log-linear relationship for the characteristic life with two stress levels.

Accelerating Vaccine Formulation Development Using Design of Experiment Stability Studies.

PubMed

Ahl, Patrick L; Mensch, Christopher; Hu, Binghua; Pixley, Heidi; Zhang, Lan; Dieter, Lance; Russell, Ryann; Smith, William J; Przysiecki, Craig; Kosinski, Mike; Blue, Jeffrey T

2016-10-01

Vaccine drug product thermal stability often depends on formulation input factors and how they interact. Scientific understanding and professional experience typically allows vaccine formulators to accurately predict the thermal stability output based on formulation input factors such as pH, ionic strength, and excipients. Thermal stability predictions, however, are not enough for regulators. Stability claims must be supported by experimental data. The Quality by Design approach of Design of Experiment (DoE) is well suited to describe formulation outputs such as thermal stability in terms of formulation input factors. A DoE approach particularly at elevated temperatures that induce accelerated degradation can provide empirical understanding of how vaccine formulation input factors and interactions affect vaccine stability output performance. This is possible even when clear scientific understanding of particular formulation stability mechanisms are lacking. A DoE approach was used in an accelerated 37(°)C stability study of an aluminum adjuvant Neisseria meningitidis serogroup B vaccine. Formulation stability differences were identified after only 15 days into the study. We believe this study demonstrates the power of combining DoE methodology with accelerated stress stability studies to accelerate and improve vaccine formulation development programs particularly during the preformulation stage. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Carqueja (Baccharis trimera) Protects against Oxidative Stress and β-Amyloid-Induced Toxicity in Caenorhabditis elegans

PubMed Central

Aparecida Paiva, Franciny; de Freitas Bonomo, Larissa; Ferreira Boasquivis, Patrícia; Borges Raposo de Paula, Igor Thadeu; Guerra, Joyce Ferreira da Costa; Mendes Leal, Wagney; Silva, Marcelo Eustáquio; Pedrosa, Maria Lúcia; Oliveira, Riva de Paula

2015-01-01

Carqueja (Baccharis trimera) is a native plant found throughout South America. Several studies have shown that Carqueja has antioxidant activity in vitro, as well as anti-inflammatory, antidiabetic, analgesic, antihepatotoxic, and antimutagenic properties. However, studies regarding its antioxidant potential in vivo are limited. In this study, we used Caenorhabditis elegans as a model to examine the antioxidant effects of a Carqueja hydroalcoholic extract (CHE) on stress resistance and lifespan and to investigate whether CHE has a protective effect in a C. elegans model for Alzheimer's disease. Here, we show for the first time, using in vivo assays, that CHE treatment improved oxidative stress resistance by increasing survival rate and by reducing ROS levels under oxidative stress conditions independently of the stress-related signaling pathways (p38, JNK, and ERK) and transcription factors (SKN-1/Nrf and DAF-16/Foxo) tested here. CHE treatment also increased the defenses against β-amyloid toxicity in C. elegans, in part by increasing proteasome activity and the expression of two heat shock protein genes. Our findings suggest a potential neuroprotective use for Carqueja, supporting the idea that dietary antioxidants are a promising approach to boost the defensive systems against stress and neurodegeneration. PMID:26236426

Effects of Adaptogens on the Central Nervous System and the Molecular Mechanisms Associated with Their Stress—Protective Activity

PubMed Central

Panossian, Alexander; Wikman, Georg

2010-01-01

Adaptogens were initially defined as substances that enhance the “state of non-specific resistance” in stress, a physiological condition that is linked with various disorders of the neuroendocrine-immune system. Studies on animals and isolated neuronal cells have revealed that adaptogens exhibit neuroprotective, anti-fatigue, antidepressive, anxiolytic, nootropic and CNS stimulating activity. In addition, a number of clinical trials demonstrate that adaptogens exert an anti-fatigue effect that increases mental work capacity against a background of stress and fatigue, particularly in tolerance to mental exhaustion and enhanced attention. Indeed, recent pharmacological studies of a number of adaptogens have provided a rationale for these effects also at the molecular level. It was discovered that the stress—protective activity of adaptogens was associated with regulation of homeostasis via several mechanisms of action, which was linked with the hypothalamic-pituitary-adrenal axis and the regulation of key mediators of stress response, such as molecular chaperons (e.g., HSP70), stress-activated c-Jun N-terminal protein kinase 1 (JNK1), Forkhead box O (FOXO) transcription factor DAF-16, cortisol and nitric oxide. PMID:27713248

Compressed sensing for high-resolution nonlipid suppressed 1 H FID MRSI of the human brain at 9.4T.

PubMed

Nassirpour, Sahar; Chang, Paul; Avdievitch, Nikolai; Henning, Anke

2018-04-29

The aim of this study was to apply compressed sensing to accelerate the acquisition of high resolution metabolite maps of the human brain using a nonlipid suppressed ultra-short TR and TE 1 H FID MRSI sequence at 9.4T. X-t sparse compressed sensing reconstruction was optimized for nonlipid suppressed 1 H FID MRSI data. Coil-by-coil x-t sparse reconstruction was compared with SENSE x-t sparse and low rank reconstruction. The effect of matrix size and spatial resolution on the achievable acceleration factor was studied. Finally, in vivo metabolite maps with different acceleration factors of 2, 4, 5, and 10 were acquired and compared. Coil-by-coil x-t sparse compressed sensing reconstruction was not able to reliably recover the nonlipid suppressed data, rather a combination of parallel and sparse reconstruction was necessary (SENSE x-t sparse). For acceleration factors of up to 5, both the low-rank and the compressed sensing methods were able to reconstruct the data comparably well (root mean squared errors [RMSEs] ≤ 10.5% for Cre). However, the reconstruction time of the low rank algorithm was drastically longer than compressed sensing. Using the optimized compressed sensing reconstruction, acceleration factors of 4 or 5 could be reached for the MRSI data with a matrix size of 64 × 64. For lower spatial resolutions, an acceleration factor of up to R∼4 was successfully achieved. By tailoring the reconstruction scheme to the nonlipid suppressed data through parameter optimization and performance evaluation, we present high resolution (97 µL voxel size) accelerated in vivo metabolite maps of the human brain acquired at 9.4T within scan times of 3 to 3.75 min. © 2018 International Society for Magnetic Resonance in Medicine.

Design, performance, and economics of 50-kW and 500-kW vertical axis wind turbines

NASA Astrophysics Data System (ADS)

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

1983-11-01

A review of the development and performance of the DAF Indal 50-kW vertical axis Darrieus wind turbine 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. Details are also presented of a 500-kW VAWT that is currently in production. A discussion of the economics of both the 50-kW and 500-kW VAWTs is included, showing the effects of charge rate, installed cost, operating cost, performance, and efficiency.

DIVWAG Model Documentation. Volume II. Programmer/Analyst Manual. Part 5.

DTIC Science & Technology

1976-07-01

Words Number Mission type: I=DAFS; 2= CAS 1 8 Estimated X coordinate of target 1 9 Estimated Y coordinate of target 1 10 Reject code: 0-mission unit... CAS 1 8 Abort indicator: O-no abort; 1-abort 1 9 X coordinate of target 1 10 " :oordinate of target 1 11 Aircraft munitions item code 6 12-17 Aircraft...L300 CALL TRNSMT U. TO TRANSMIT FIRST BLOCK OF DATA L100 YES REQUEST FOR INPU? LIOI CA " TRAN21I TO TRANSMIT LAST BLOCK OF DATA Figure VII-3-B- 10

Determination of the needed power of an electric motor on the basis of acceleration time of the electric car

NASA Astrophysics Data System (ADS)

Sapundzhiev, M.; Evtimov, I.; Ivanov, R.

2017-10-01

The paper presents an upgraded methodology for determination of the electric motor power considering the time for acceleration. The influence of the speed factor of electric motor on the value of needed power at same acceleration time is studied. Some calculations on the basis of real vehicle were made. The numeric and graphical results are given. They show a decrease of needed power with the increase of the speed factor of motor, because the high speed factor allows the use of a larger range of the characteristic with the maximum power of the motor. An experimental verification of methodology was done.

Accelerators (4/5)

ScienceCinema

Metral, Elias

2017-12-09

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 Prerequisite knowledge: Previous knowledge of accelerators is not required.

Accelerators (5/5)

ScienceCinema

None

2018-05-16

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 Prerequisite knowledge: Previous knowledge of accelerators is not required.

Investigation of carbohydrate and protein metabolism in the digestive organs of the rabbit under the combined influence of vibration, acceleration and irradiation

NASA Technical Reports Server (NTRS)

Yuy, R. I.

1975-01-01

During spaceflight, the organism is subjected to the influence of various extremal factors such as acceleration, vibration, irradiation, etc. The study of the influence of these factors on metabolism, especially carbohydrate and protein metabolism, in young rabbits is of great significance in simulation experiments. Dynamic factors and irradiation, depending on dose and duration, lead to reduced RNA and protein metabolism.

The course of experimental staphylococcus infection in albino mice during action of certain factors of space flight

NASA Technical Reports Server (NTRS)

Prokhorov, V. Y.; Shilov, V. M.; Borman, E. A.

1980-01-01

A study was made of the effect of certain factors of space flight, acceleration and hypokinesia, on the course of experimental staphylococcus infection in mice. Combined action of hypokinesia and acceleration caused a marked depression of the phagocytic activity of leukocytes and formation of a considerable amount of alpha toxin.

Phosphorus uptake, partitioning and redistribution during grain filling in rice

PubMed Central

Julia, Cécile; Wissuwa, Matthias; Kretzschmar, Tobias; Jeong, Kwanho; Rose, Terry

2016-01-01

Backgrounds and Aims In cultivated rice, phosphorus (P) in grains originates from two possible sources, namely exogenous (post-flowering root P uptake from soil) or endogenous (P remobilization from vegetative parts) sources. This study investigates P partitioning and remobilization in rice plants throughout grain filling to resolve contributions of P sources to grain P levels in rice. Methods Rice plants (Oryza sativa ‘IR64’) were grown under P-sufficient or P-deficient conditions in the field and in hydroponics. Post-flowering uptake, partitioning and re-partitioning of P was investigated by quantifying tissue P levels over the grain filling period in the field conditions, and by employing 33P isotope as a tracer in the hydroponic study. Key Results Post-flowering P uptake represented 40–70 % of the aerial plant P accumulation at maturity. The panicle was the main P sink in all studies, and the amount of P potentially remobilized from vegetative tissues to the panicle during grain filling was around 20 % of the total aerial P measured at flowering. In hydroponics, less than 20 % of the P tracer taken up at 9 d after flowering (DAF) was found in the above-ground tissues at 14 DAF and half of it was partitioned to the panicle in both P treatments. Conclusions The results demonstrate that P uptake from the soil during grain filling is a critical contributor to the P content in grains in irrigated rice. The P tracer study suggests that the mechanism of P loading into grains involves little direct transfer of post-flowering P uptake to the grain but rather substantial mobilization of P that was previously taken up and stored in vegetative tissues. PMID:27590335

Differentiation-dependent expression of hypothetical proteins in the neuroblastoma cell line N1E-115.

PubMed

Oh, Ji-eun; Karlmark, Karlin Raja; Shin, Jooho; Hengstschläger, Markus; Lubec, Gert

2006-05-15

Several protein cascades, including signaling, cytoskeletal, chaperones, metabolic, and antioxidant proteins, have been shown to be involved in the process of neuronal differentiation (ND) of neuroblastoma cell lines. No systematic approach to detect hitherto unknown and unnamed proteins or structures that have been predicted upon nucleic acid sequences in ND has been published so far. We therefore decided to screen hypothetical protein (HP) expression by protein profiling. Two-dimensional gel electrophoresis with subsequent matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF/TOF) identification was used for expression analysis of undifferentiated and dimethylsulfoxide-induced neuronally differentiated N1E-115 cells. We unambiguously identified six HPs: Q8C520, Q99LF4, Q9CXS1, Q9DAF8, Q91WT0, and Q8C5G2. A prefoldin domain in Q91WT0, a t-SNARE domain in Q9CXS1, and a bromodomain were observed in Q8C5G2. For the three remaining proteins, no putative function using Pfam, BLOCKS, PROSITE, PRINTS, InterPro, Superfamily, CoPS, and ExPASy could be assigned. While two proteins were present in both cell lines, Q9CXS1 was switched off (i.e., undetectably low) in differentiated cells only, and Q9DAF8, Q91WT0, and Q8C5G2 were switched on in differentiated cells exclusively. Herein, using a proteomic approach suitable for screening and identification of HP, we present HP structures that have been only predicted so far based upon nucleic acid sequences. The four differentially regulated HPs may play a putative role in the process of ND. (c) 2006 Wiley-Liss, Inc.

Natural variation in gene expression in the early development of dauer larvae of Caenorhabditis elegans.

PubMed

Harvey, Simon C; Barker, Gary L A; Shorto, Alison; Viney, Mark E

2009-07-18

The free-living nematode Caenorhabditis elegans makes a developmental decision based on environmental conditions: larvae either arrest as dauer larva, or continue development into reproductive adults. There is natural variation among C. elegans lines in the sensitivity of this decision to environmental conditions; that is, there is variation in the phenotypic plasticity of dauer larva development. We hypothesised that these differences may be transcriptionally controlled in early stage larvae. We investigated this by microarray analysis of different C. elegans lines under different environmental conditions, specifically the presence and absence of dauer larva-inducing pheromone. There were substantial transcriptional differences between four C. elegans lines under the same environmental conditions. The expression of approximately 2,000 genes differed between genetically different lines, with each line showing a largely line-specific transcriptional profile. The expression of genes that are markers of larval moulting suggested that the lines may be developing at different rates. The expression of a total of 89 genes was putatively affected by dauer larva or non-dauer larva-inducing conditions. Among the upstream regions of these genes there was an over-representation of DAF-16-binding motifs. Under the same environmental conditions genetically different lines of C. elegans had substantial transcriptional differences. This variation may be due to differences in the developmental rates of the lines. Different environmental conditions had a rather smaller effect on transcription. The preponderance of DAF-16-binding motifs upstream of these genes was consistent with these genes playing a key role in the decision between development into dauer or into non-dauer larvae. There was little overlap between the genes whose expression was affected by environmental conditions and previously identified loci involved in the plasticity of dauer larva development.

Effect of GA3 treatment on seed development and seed-related gene expression in grape.

PubMed

Cheng, Chenxia; Xu, Xiaozhao; Singer, Stacy D; Li, Jun; Zhang, Hongjing; Gao, Min; Wang, Li; Song, Junyang; Wang, Xiping

2013-01-01

The phytohormone gibberellic acid (GA3) is widely used in the table grape industry to induce seedlessness in seeded varieties. However, there is a paucity of information concerning the mechanisms by which GAs induce seedlessness in grapes. In an effort to systematically analyze the cause of this GA3-induced seed abortion, we conducted an in depth characterization of two seeded grape cultivars ('Kyoho' and 'Red Globe'), along with a seedless cultivar ('Thompson Seedless'), following treatment with GA3. In a similar fashion to the seedless control, which exhibited GA3-induced abortion of the seeds 9 days after full bloom (DAF), both 'Kyoho' and 'Red Globe' seeded varieties exhibited complete abortion of the seeds 15 DAF when treated with GA3. Morphological analyses indicated that while fertilization appeared to occur normally following GA3 treatment, as well as in the untreated seedless control cultivar, seed growth eventually ceased. In addition, we found that GA3 application had an effect on redox homeostasis, which could potentially cause cell damage and subsequent seed abortion. Furthermore, we carried out an analysis of antioxidant enzyme activities, as well as transcript levels from various genes believed to be involved in seed development, and found several differences between GA3-treated and untreated controls. Therefore, it seems that the mechanisms driving GA3-induced seedlessness are similar in both seeded and seedless cultivars, and that the observed abortion of seeds may result at least in part from a GA3-induced increase in cell damage caused by reactive oxygen species, a decrease in antioxidant enzymatic activities, and an alteration of the expression of genes related to seed development.

Effect of GA3 Treatment on Seed Development and Seed-Related Gene Expression in Grape

PubMed Central

Cheng, Chenxia; Xu, Xiaozhao; Singer, Stacy D.; Li, Jun; Zhang, Hongjing; Gao, Min; Wang, Li; Song, Junyang; Wang, Xiping

2013-01-01

Background The phytohormone gibberellic acid (GA3) is widely used in the table grape industry to induce seedlessness in seeded varieties. However, there is a paucity of information concerning the mechanisms by which GAs induce seedlessness in grapes. Methodology/Principal Findings In an effort to systematically analyze the cause of this GA3-induced seed abortion, we conducted an in depth characterization of two seeded grape cultivars (‘Kyoho’ and ‘Red Globe’), along with a seedless cultivar (‘Thompson Seedless’), following treatment with GA3. In a similar fashion to the seedless control, which exhibited GA3-induced abortion of the seeds 9 days after full bloom (DAF), both ‘Kyoho’ and ‘Red Globe’ seeded varieties exhibited complete abortion of the seeds 15 DAF when treated with GA3. Morphological analyses indicated that while fertilization appeared to occur normally following GA3 treatment, as well as in the untreated seedless control cultivar, seed growth eventually ceased. In addition, we found that GA3 application had an effect on redox homeostasis, which could potentially cause cell damage and subsequent seed abortion. Furthermore, we carried out an analysis of antioxidant enzyme activities, as well as transcript levels from various genes believed to be involved in seed development, and found several differences between GA3-treated and untreated controls. Conclusion Therefore, it seems that the mechanisms driving GA3-induced seedlessness are similar in both seeded and seedless cultivars, and that the observed abortion of seeds may result at least in part from a GA3-induced increase in cell damage caused by reactive oxygen species, a decrease in antioxidant enzymatic activities, and an alteration of the expression of genes related to seed development. PMID:24224035

Analysis of gene expression profiles of two near-isogenic lines differing at a QTL region affecting oil content at high temperatures during seed maturation in oilseed rape (Brassica napus L.).

PubMed

Zhu, Yana; Cao, Zhengying; Xu, Fei; Huang, Yi; Chen, Mingxun; Guo, Wanli; Zhou, Weijun; Zhu, Jun; Meng, Jinling; Zou, Jitao; Jiang, Lixi

2012-02-01

Seed oil production in oilseed rape is greatly affected by the temperature during seed maturation. However, the molecular mechanism of the interaction between genotype and temperature in seed maturation remains largely unknown. We developed two near-isogenic lines (NIL-9 and NIL-1), differing mainly at a QTL region influencing oil content on Brassica napus chromosome C2 (qOC.C2.2) under high temperature during seed maturation. The NILs were treated under different temperatures in a growth chamber after flowering. RNA from developing seeds was extracted on the 25th day after flowering (DAF), and transcriptomes were determined by microarray analysis. Statistical analysis indicated that genotype, temperature, and the interaction between genotype and temperature (G × T) all significantly affected the expression of the genes in the 25 DAF seeds, resulting in 4,982, 19,111, and 839 differentially expressed unisequences, respectively. NIL-9 had higher seed oil content than NIL-1 under all of the temperatures in the experiments, especially at high temperatures. A total of 39 genes, among which six are located at qOC.C2.2, were differentially expressed among the NILs regardless of temperature, indicating the core genetic divergence that was unaffected by temperature. Increasing the temperature caused a reduction in seed oil content that was accompanied by the downregulation of a number of genes associated with red light response, photosynthesis, response to gibberellic acid stimulus, and translational elongation, as well as several genes of importance in the lipid metabolism pathway. These results contribute to our knowledge of the molecular nature of QTLs and the interaction between genotype and temperature.

Hypotonic swelling promotes nitric oxide release in cardiac ventricular myocytes: impact on swelling-induced negative inotropic effect

PubMed Central

Gonano, Luis Alberto; Morell, Malena; Burgos, Juan Ignacio; Dulce, Raul Ariel; De Giusti, Verónica Celeste; Aiello, Ernesto Alejandro; Hare, Joshua Michael; Vila Petroff, Martin

2014-01-01

Aims Cardiomyocyte swelling occurs in multiple pathological situations and has been associated with contractile dysfunction, cell death, and enhanced propensity to arrhythmias. We investigate whether hypotonic swelling promotes nitric oxide (NO) release in cardiomyocytes, and whether it impacts on swelling-induced contractile dysfunction. Methods and results Superfusing rat cardiomyocytes with a hypotonic solution (HS; 217 mOsm), increased cell volume, reduced myocyte contraction and Ca2+ transient, and increased NO-sensitive 4-amino-5-methylamino-2′,7′-difluorofluorescein diacetate (DAF-FM) fluorescence. When cells were exposed to HS + 2.5 mM of the NO synthase inhibitor l-NAME, cell swelling occurred in the absence of NO release. Swelling-induced NO release was also prevented by the nitric oxide synthase 1 (NOS1) inhibitor, nitroguanidine, and significantly reduced in NOS1 knockout mice. Additionally, colchicine (inhibitor of microtubule polymerization) prevented the increase in DAF-FM fluorescence induced by HS, indicating that microtubule integrity is necessary for swelling-induced NO release. The swelling-induced negative inotropic effect was exacerbated in the presence of either l-NAME, nitroguandine, the guanylate cyclase inhibitor, ODQ, or the PKG inhibitor, KT5823, suggesting that NOS1-derived NO provides contractile support via a cGMP/PKG-dependent mechanism. Indeed, ODQ reduced Ca2+ wave velocity and both ODQ and KT5823 reduced the HS-induced increment in ryanodine receptor (RyR2, Ser2808) phosphorylation, suggesting that in this context, cGMP/PKG may contribute to preserve contractile function by enhancing sarcoplasmic reticulum Ca2+ release. Conclusions Our findings suggest a novel mechanism for NO release in cardiomyocytes with putative pathophysiological relevance determined, at least in part, by its capability to reduce the extent of contractile dysfunction associated with hypotonic swelling. PMID:25344365

S6K links cell fate, cell cycle and nutrient response in C. elegans germline stem/progenitor cells

PubMed Central

Korta, Dorota Z.; Tuck, Simon; Hubbard, E. Jane Albert

2012-01-01

Coupling of stem/progenitor cell proliferation and differentiation to organismal physiological demands ensures the proper growth and homeostasis of tissues. However, in vivo mechanisms underlying this control are poorly characterized. We investigated the role of ribosomal protein S6 kinase (S6K) at the intersection of nutrition and the establishment of a stem/progenitor cell population using the C. elegans germ line as a model. We find that rsks-1 (which encodes the worm homolog of mammalian p70S6K) is required germline-autonomously for proper establishment of the germline progenitor pool. In the germ line, rsks-1 promotes cell cycle progression and inhibits larval progenitor differentiation, promotes growth of adult tumors and requires a conserved TOR phosphorylation site. Loss of rsks-1 and ife-1 (eIF4E) together reduces the germline progenitor pool more severely than either single mutant and similarly to reducing the activity of let-363 (TOR) or daf-15 (RAPTOR). Moreover, rsks-1 acts in parallel with the glp-1 (Notch) and daf-2 (insulin-IGF receptor) pathways, and does not share the same genetic dependencies with its role in lifespan control. We show that overall dietary restriction and amino acid deprivation cause germline defects similar to a subset of rsks-1 mutant phenotypes. Consistent with a link between diet and germline proliferation via rsks-1, loss of rsks-1 renders the germ line largely insensitive to the effects of dietary restriction. Our studies establish the C. elegans germ line as an in vivo model to understand TOR-S6K signaling in proliferation and differentiation and suggest that this pathway is a key nutrient-responsive regulator of germline progenitors. PMID:22278922

Hormonal Signal Amplification Mediates Environmental Conditions during Development and Controls an Irreversible Commitment to Adulthood

PubMed Central

Schaedel, Oren N.; Gerisch, Birgit; Antebi, Adam; Sternberg, Paul W.

2012-01-01

Many animals can choose between different developmental fates to maximize fitness. Despite the complexity of environmental cues and life history, different developmental fates are executed in a robust fashion. The nematode Caenorhabditis elegans serves as a powerful model to examine this phenomenon because it can adopt one of two developmental fates (adulthood or diapause) depending on environmental conditions. The steroid hormone dafachronic acid (DA) directs development to adulthood by regulating the transcriptional activity of the nuclear hormone receptor DAF-12. The known role of DA suggests that it may be the molecular mediator of environmental condition effects on the developmental fate decision, although the mechanism is yet unknown. We used a combination of physiological and molecular biology techniques to demonstrate that commitment to reproductive adult development occurs when DA levels, produced in the neuroendocrine XXX cells, exceed a threshold. Furthermore, imaging and cell ablation experiments demonstrate that the XXX cells act as a source of DA, which, upon commitment to adult development, is amplified and propagated in the epidermis in a DAF-12 dependent manner. This positive feedback loop increases DA levels and drives adult programs in the gonad and epidermis, thus conferring the irreversibility of the decision. We show that the positive feedback loop canalizes development by ensuring that sufficient amounts of DA are dispersed throughout the body and serves as a robust fate-locking mechanism to enforce an organism-wide binary decision, despite noisy and complex environmental cues. These mechanisms are not only relevant to C. elegans but may be extended to other hormonal-based decision-making mechanisms in insects and mammals. PMID:22505848

Toxicity interactions between manganese (Mn) and lead (Pb) or cadmium (Cd) in a model organism the nematode C. elegans.

PubMed

Lu, Cailing; Svoboda, Kurt R; Lenz, Kade A; Pattison, Claire; Ma, Hongbo

2018-06-01

Manganese (Mn) is considered as an emerging metal contaminant in the environment. However, its potential interactions with companying toxic metals and the associated mixture effects are largely unknown. Here, we investigated the toxicity interactions between Mn and two commonly seen co-occurring toxic metals, Pb and Cd, in a model organism the nematode Caenorhabditis elegans. The acute lethal toxicity of mixtures of Mn+Pb and Mn+Cd were first assessed using a toxic unit model. Multiple toxicity endpoints including reproduction, lifespan, stress response, and neurotoxicity were then examined to evaluate the mixture effects at sublethal concentrations. Stress response was assessed using a daf-16::GFP transgenic strain that expresses GFP under the control of DAF-16 promotor. Neurotoxicity was assessed using a dat-1::GFP transgenic strain that expresses GFP in dopaminergic neurons. The mixture of Mn+Pb induced a more-than-additive (synergistic) lethal toxicity in the worm whereas the mixture of Mn+Cd induced a less-than-additive (antagonistic) toxicity. Mixture effects on sublethal toxicity showed more complex patterns and were dependent on the toxicity endpoints as well as the modes of toxic action of the metals. The mixture of Mn+Pb induced additive effects on both reproduction and lifespan, whereas the mixture of Mn+Cd induced additive effects on lifespan but not reproduction. Both mixtures seemed to induce additive effects on stress response and neurotoxicity, although a quantitative assessment was not possible due to the single concentrations used in mixture tests. Our findings demonstrate the complexity of metal interactions and the associated mixture effects. Assessment of metal mixture toxicity should take into consideration the unique property of individual metals, their potential toxicity mechanisms, and the toxicity endpoints examined.

Effect of Debagging Time on Pigment Patterns in the Peel and Sugar and Organic Acid Contents in the Pulp of ‘Golden Delicious’ and ‘Qinguan’ Apple Fruit at Mid and Late Stages of Development

PubMed Central

Jing, Chenjuan; Ma, Changqing; Zhang, Juan; Jing, Shujuan; Jiang, Xiaobing; Yang, Yazhou; Zhao, Zhengyang

2016-01-01

This study examined the effect of debagging time on color and flavor / taste compounds in the non-red apple cultivar ‘Golden Delicious’ and red cultivar ‘Qinguan’ at mid and late stages of fruit development. Debagging briefly improved the red color in both cultivars, the peel of ‘Golden Delicious’ presenting pale-pink hue. However, rapid anthocyanin accumulation occurred in apple peel at a specific time (after 179 days after flowering (DAF) in ‘Qinguan’) and was unaltered by debagging time in the red cultivar ‘Qinguan’. Furthermore, untimely debagging had a detrimental effect on the content of anthocyanin. All sugars increased and organic acids decreased in apple pulp at mid to late stages of development. Bagging treatment reduced the content of most sugars and organic acids, as well as, the overall total. However, glucose and citric acid contents were higher in bagged fruit than non-bagged fruit; the maximum occurred in T7 treatment that was no-debagging at DAF 159 / 196 (‘Golden delicious’ / ‘Qinguan’), i.e., 24.35 and 0.07 mg g-1 FW in ‘Golden delicious’, and 38.86 and 0.06 mg g-1 FW in ‘Qinguan’, respectively. In a word, bagging treatment can alter the pattern of peel color development in apple fruit; however, it remains difficult to alter the timing of rapid anthocyanin accumulation as it is regulated solely by development. Moreover, bagging treatment reduced the total accumulation of sugars and organic acids, and even the over total in pulp, but increased the glucose and citric acid contents in apple pulp. PMID:27788164

Randomized study combining interferon and glatiramer acetate in multiple sclerosis.

PubMed

Lublin, Fred D; Cofield, Stacey S; Cutter, Gary R; Conwit, Robin; Narayana, Ponnada A; Nelson, Flavia; Salter, Amber R; Gustafson, Tarah; Wolinsky, Jerry S

2013-03-01

A double-blind, randomized, controlled study was undertaken to determine whether combined use of interferon β-1a (IFN) 30 μg intramuscularly weekly and glatiramer acetate (GA) 20 mg daily is more efficacious than either agent alone in relapsing-remitting multiple sclerosis. A total of 1,008 participants were randomized and followed until the last participant enrolled completed 3 years. The primary endpoint was reduction in annualized relapse rate utilizing a strict definition of relapse. Secondary outcomes included time to confirmed disability, Multiple Sclerosis Functional Composite (MSFC) score, and magnetic resonance imaging (MRI) metrics. Combination IFN+GA was not superior to the better of the single agents (GA) in risk of relapse. Both the combination therapy and GA were significantly better than IFN in reducing the risk of relapse. The combination was not better than either agent alone in lessening confirmed Expanded Disability Status Scale progression or change in MSFC over 36 months. The combination was superior to either agent alone in reducing new lesion activity and accumulation of total lesion volumes. In a post hoc analysis, combination therapy resulted in a higher proportion of participants attaining disease activity-free status (DAFS) compared to either single arm, driven by the MRI results. Combining the 2 most commonly prescribed therapies for multiple sclerosis did not produce a significant clinical benefit over 3 years. An effect was seen on some MRI metrics. In a test of comparative efficacy, GA was superior to IFN in reducing the risk of exacerbation. The extension phase for CombiRx will address whether the observed differences in MRI and DAFS findings predict later clinical differences. Copyright © 2013 American Neurological Association.

Isolation of the endosperm-specific LPAAT gene promoter from coconut (Cocos nucifera L.) and its functional analysis in transgenic rice plants.

PubMed

Xu, Li; Ye, Rongjian; Zheng, Yusheng; Wang, Zhekui; Zhou, Peng; Lin, Yongjun; Li, Dongdong

2010-09-01

As one of the key tropical crops, coconut (Cocos nucifera L.) is a member of the monocotyledonous family Aracaceae (Palmaceae). In this study, we amplified the upstream region of an endosperm-specific expression gene, Lysophosphatidyl acyltransferase (LPAAT), from the coconut genomic DNA by chromosome walking. In this sequence, we found several types of promoter-related elements including TATA-box, CAAT-box and Skn1-motif. In order to further examine its function, three different 5'-deletion fragments were inserted into pBI101.3, a plant expression vector harboring the LPAAT upstream sequence, leading to pBI101.3-L1, pBI101.3-L2 and pBI101.3-L3, respectively. We obtained transgenic plants of rice by Agrobacterium-mediated callus transformation and plant regeneration and detected the expression of gus gene by histochemical staining and fluorometric determination. We found that gus gene driven by the three deletion fragments was specifically expressed in the endosperm of rice seeds, but not in the empty vector of pBI101.3 and other tissues. The highest expression level of GUS was at 15 DAF in pBI101.3-L3 and pBI101.3-L2 transgenic lines, while the same level was detected at 10 DAF in pBI101.3-L1. The expression driven by the whole fragment was up to 1.76- and 2.8-fold higher than those driven by the -817 bp and -453 bp upstream fragments, and 10.7-fold higher than that driven by the vector without the promoter. Taken together, our results strongly suggest that these promoter fragments from coconut have a significant potential in genetically improving endosperm in main crops.

Generation of α-1,3-galactosyltransferase knocked-out transgenic cloned pigs with knocked-in five human genes.

PubMed

Kwon, Dae-Jin; Kim, Dong-Hwan; Hwang, In-Sul; Kim, Dong-Ern; Kim, Hyung-Joo; Kim, Jang-Seong; Lee, Kichoon; Im, Gi-Sun; Lee, Jeong-Woong; Hwang, Seongsoo

2017-02-01

Recent progress in genetic manipulation of pigs designated for xenotransplantation ha6s shown considerable promise on xenograft survival in primates. However, genetic modification of multiple genes in donor pigs by knock-out and knock-in technologies, aiming to enhance immunological tolerance against transplanted organs in the recipients, has not been evaluated for health issues of donor pigs. We produced transgenic Massachusetts General Hospital piglets by knocking-out the α-1,3-galactosyltransferase (GT) gene and by simultaneously knocking-in an expression cassette containing five different human genes including, DAF, CD39, TFPI, C1 inhibitor (C1-INH), and TNFAIP3 (A20) [GT -(DAF/CD39/TFPI/C1-INH/TNFAIP3)/+ ] that are connected by 2A peptide cleavage sequences to release individual proteins from a single translational product. All five individual protein products were successfully produced as determined by western blotting of umbilical cords from the newborn transgenic pigs. Although gross observation and histological examination revealed no significant pathological abnormality in transgenic piglets, hematological examination found that the transgenic piglets had abnormally low numbers of platelets and WBCs, including neutrophils, eosinophils, basophils, and lymphocytes. However, transgenic piglets had similar numbers of RBC and values of parameters related to RBC compared to the control littermate piglets. These data suggest that transgenic expression of those human genes in pigs impaired hematopoiesis except for erythropoiesis. In conclusion, our data suggest that transgenic expression of up to five different genes can be efficiently achieved and provide the basis for determining optimal dosages of transgene expression and combinations of the transgenes to warrant production of transgenic donor pigs without health issues.

Coronal tibial slope is associated with accelerated knee osteoarthritis: data from the Osteoarthritis Initiative.

PubMed

Driban, Jeffrey B; Stout, Alina C; Duryea, Jeffrey; Lo, Grace H; Harvey, William F; Price, Lori Lyn; Ward, Robert J; Eaton, Charles B; Barbe, Mary F; Lu, Bing; McAlindon, Timothy E

2016-07-19

Accelerated knee osteoarthritis may be a unique subset of knee osteoarthritis, which is associated with greater knee pain and disability. Identifying risk factors for accelerated knee osteoarthritis is vital to recognizing people who will develop accelerated knee osteoarthritis and initiating early interventions. The geometry of an articular surface (e.g., coronal tibial slope), which is a determinant of altered joint biomechanics, may be an important risk factor for incident accelerated knee osteoarthritis. We aimed to determine if baseline coronal tibial slope is associated with incident accelerated knee osteoarthritis or common knee osteoarthritis. We conducted a case-control study using data and images from baseline and the first 4 years of follow-up in the Osteoarthritis Initiative. We included three groups: 1) individuals with incident accelerated knee osteoarthritis, 2) individuals with common knee osteoarthritis progression, and 3) a control group with no knee osteoarthritis at any time. We did 1:1:1 matching for the 3 groups based on sex. Weight-bearing, fixed flexion posterior-anterior knee radiographs were obtained at each visit. One reader manually measured baseline coronal tibial slope on the radiographs. Baseline femorotibial angle was measured on the radiographs using a semi-automated program. To assess the relationship between slope (predictor) and incident accelerated knee osteoarthritis or common knee osteoarthritis (outcomes) compared with no knee osteoarthritis (reference outcome), we performed multinomial logistic regression analyses adjusted for sex. The mean baseline slope for incident accelerated knee osteoarthritis, common knee osteoarthritis, and no knee osteoarthritis were 3.1(2.0), 2.7(2.1), and 2.6(1.9); respectively. A greater slope was associated with an increased risk of incident accelerated knee osteoarthritis (OR = 1.15 per degree, 95 % CI = 1.01 to 1.32) but not common knee osteoarthritis (OR = 1.04, 95 % CI = 0.91 to 1.19). These findings were similar when adjusted for recent injury. Among knees with varus malalignment a greater slope increases the odds of incident accelerated knee osteoarthritis; there is no significant relationship between slope and incident accelerated knee osteoarthritis among knees with normal alignment. Coronal tibial slope, particularly among knees with malalignment, may be an important risk factor for incident accelerated knee osteoarthritis.

Human Cytomegalovirus Secretome Contains Factors That Induce Angiogenesis and Wound Healing

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

Dumortier, Jerome; Streblow, Daniel N.; Moses, Ashlee V.

2008-07-01

Human cytomegalovirus (HCMV) is implicated in the acceleration of a number of vascular diseases including transplant vascular sclerosis (TVS), the lesion associated with chronic rejection (CR) of solid organ transplants. Although the virus persists in the allograft throughout the course of disease, few cells are directly infected by CMV. This observation is in contrast to the global effects that CMV has on the acceleration of TVS/CR, suggesting that CMV infection indirectly promotes the vascular disease process. Recent transcriptome analysis of CMV-infected heart allografts indicates that the virus induces cytokines and growth factors associated with angiogenesis (AG) and wound healing (WH),more » suggesting that CMV may accelerate TVS/CR through the induction and secretion of AG/WH factors from infected cells. We analyzed virus-free supernatants from HCMV-infected cells (HCMV secretomes) for growth factors, by mass spectrometry and immunoassays, and found that the HCMV secretome contains over 1,000 cellular proteins, many of which are involved in AG/WH. Importantly, functional assays demonstrated that CMV but not herpes simplex virus secretomes not only induce AG/WH but also promote neovessel stabilization and endothelial cell survival for 2 weeks. These findings suggest that CMV acceleration of TVS occurs through virus-induced growth factors and cytokines in the CMV secretome.« less

Ultra-high quality factors in superconducting niobium cavities in ambient magnetic fields up to 190 mG

DOE PAGES

Romanenko, A.; Grassellino, A.; Crawford, A. C.; ...

2014-12-10

Ambient magnetic field, if trapped in the penetration depth, leads to the residual resistance and therefore sets the limit for the achievable quality factors in superconducting niobium resonators for particle accelerators. Here, we show that a complete expulsion of the magnetic flux can be performed and leads to: (1) record quality factors Q > 2 x 10¹¹ up to accelerating gradient of 22 MV/m; (2) Q ~ 3 x 10¹⁰ at 2 K and 16 MV/m in up to 190 mG magnetic fields. This is achieved by large thermal gradients at the normal/superconducting phase front during the cooldown. Our findingsmore » open up a way to ultra-high quality factors at low temperatures and show an alternative to the sophisticated magnetic shielding implemented in modern superconducting accelerators.« less

Modifying effect of dynamic space flight factors on radiation damage of air-dry seeds of Crepis capillaris (L) Wallr.

PubMed

Vaulina, E N; Kostina, L N

1975-01-01

The influence of dynamic factors (vibration and linear acceleration) on the rate of chromosome aberrations in Crepis capillaris was studied. The vibrational process simulated was similar in its characteristics to that occurring at the launch of spaceships. In combination with linear acceleration it caused a statistically significant increase in the rate of chromosome aberrations compared with the control (R=7.70). The dynamic factors modified the effect of radiation damage induced by acute gamma-irradiation (3 krad). Pre-radiation treatment with vibration and acceleration on the seeds caused a significant decrease (R=10.23) of the effect of radiation damage, from 15.57% to 9.74%. The post-radiation treatment of C. capillaris seeds with the dynamic factors did not change the rate of chromosome aberrations significantly (from 15.57% to 15.90%).

Double temporal sparsity based accelerated reconstruction of compressively sensed resting-state fMRI.

PubMed

Aggarwal, Priya; Gupta, Anubha

2017-12-01

A number of reconstruction methods have been proposed recently for accelerated functional Magnetic Resonance Imaging (fMRI) data collection. However, existing methods suffer with the challenge of greater artifacts at high acceleration factors. This paper addresses the issue of accelerating fMRI collection via undersampled k-space measurements combined with the proposed method based on l 1 -l 1 norm constraints, wherein we impose first l 1 -norm sparsity on the voxel time series (temporal data) in the transformed domain and the second l 1 -norm sparsity on the successive difference of the same temporal data. Hence, we name the proposed method as Double Temporal Sparsity based Reconstruction (DTSR) method. The robustness of the proposed DTSR method has been thoroughly evaluated both at the subject level and at the group level on real fMRI data. Results are presented at various acceleration factors. Quantitative analysis in terms of Peak Signal-to-Noise Ratio (PSNR) and other metrics, and qualitative analysis in terms of reproducibility of brain Resting State Networks (RSNs) demonstrate that the proposed method is accurate and robust. In addition, the proposed DTSR method preserves brain networks that are important for studying fMRI data. Compared to the existing methods, the DTSR method shows promising potential with an improvement of 10-12 dB in PSNR with acceleration factors upto 3.5 on resting state fMRI data. Simulation results on real data demonstrate that DTSR method can be used to acquire accelerated fMRI with accurate detection of RSNs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Microdroplet fusion mass spectrometry: accelerated kinetics of acid-induced chlorophyll demetallation

PubMed Central

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. PMID:29233214

Microdroplet fusion mass spectrometry: accelerated kinetics of acid-induced chlorophyll demetallation.

PubMed

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.

Trends in der IT-Sicherheit

NASA Astrophysics Data System (ADS)

Eckert, Claudia

Ich möchte Ihnen einen Überblick geben über Trends, Challenges, offene Fragestellungen sowie Lösungsansätze aus dem Bereich der IT-Sicherheit. Meine Vorredner haben mir schon eine wunderbare Basis dafür geschaffen, indem sie wichtige Trends im Bereich IT bereits angesprochen haben. Deshalb werde ich auf diese Trends, nämlich das Internet of Things and Services nur noch einmal kurz eingehen, um daran dann die IT-Sicherheitsthemen, die sich aus diesen IT-Trends ergeben, zu skizzieren und anschließend Lösungen vorstellen, die insbesondere im Forschungsumfeld entwickelt werden, aber schon reif sind, auch in die unternehmerische Praxis übernommen zu werden.

Alternative Antriebe für Automobile: Hybridsysteme, Brennstoffzellen, alternative Energieträger

NASA Astrophysics Data System (ADS)

Stan, Cornel

Über die Realisierungsmöglichkeiten zukünftiger Antriebskonzepte - von Hybridsystemen Elektro-/Verbrennungsmotor über Brennstoffzellen bis zu alternativen Energieträgern wie Wasserstoff oder Alkohol - werden fundierte Kriterien der Qualität eines Antriebs entscheiden. Leistungsdichte, Drehmomentverlauf, Beschleunigungscharakteristik, spezifischer Energieverbrauch sowie Emission chemischer Stoffe und Geräusche sind dafür wichtige Merkmale zur Qualitätsbeurteilung. Die Verfügbarkeit und die Speicherfähigkeit vorgesehener Energieträger, die technische Komplexität, Kosten, Sicherheit, Infrastruktur und Service werden die Randbedingungen für die Einführung realisierbarer Konzepte alternativer Antriebe für Automobile stellen.

SU-E-T-223: High-Energy Photon Standard Dosimetry Data: A Quality Assurance Tool.

PubMed

Lowenstein, J; Kry, S; Molineu, A; Alvarez, P; Aguirre, J; Summers, P; Followill, D

2012-06-01

Describe the Radiological Physics Center's (RPC) extensive standard dosimetry data set determined from on-site audits measurements. Measurements were made during on-site audits to institutions participating in NCI funded cooperative clinical trials for 44 years using a 0.6cc cylindrical ionization chamber placed within the RPC's water tank. Measurements were made on Varian, Siemens, and Elekta/Philips accelerators for 11 different energies from 68 models of accelerators. We have measured percent depth dose, output factors, and off-axis factors for 123 different accelerator model/energy combinations for which we have 5 or more sets of measurements. The RPC analyzed these data and determined the 'standard data' for each model/energy combination. The RPC defines 'standard data' as the mean value of 5 or more sets of dosimetry data or agreement with published depth dose data (within 2%). The analysis of these standard data indicates that for modern accelerator models, the dosimetry data for a particular model/energy are within ï,±2%. The RPC has always found accelerators of the same make/model/energy combination have the same dosimetric properties in terms of depth dose, field size dependence and off-axis factors. Because of this consistency, the RPC can assign standard data for percent depth dose, average output factors and off-axis factors for a given combination of energy and accelerator make and model. The RPC standard data can be used as a redundant quality assurance tool to assist Medical Physicists to have confidence in their clinical data to within 2%. The next step is for the RPC to provide a way for institutions to submit data to the RPC to determine if their data agrees with the standard data as a redundant check. This work was supported by PHS grants CA10953 awarded by NCI, DHHS. © 2012 American Association of Physicists in Medicine.

Accelerated Fractional Ventilation Imaging with Hyperpolarized Gas MRI

PubMed Central

Emami, Kiarash; Xu, Yinan; Hamedani, Hooman; Profka, Harrilla; Kadlecek, Stephen; Xin, Yi; Ishii, Masaru; Rizi, Rahim R.

2013-01-01

PURPOSE To investigate the utility of accelerated imaging to enhance multi-breath fractional ventilation (r) measurement accuracy using HP gas MRI. Undersampling shortens the breath-hold time, thereby reducing the O2-induced signal decay and allows subjects to maintain a more physiologically relevant breathing pattern. Additionally it may improve r estimation accuracy by reducing RF destruction of HP gas. METHODS Image acceleration was achieved by using an 8-channel phased array coil. Undersampled image acquisition was simulated in a series of ventilation images and images were reconstructed for various matrix sizes (48–128) using GRAPPA. Parallel accelerated r imaging was also performed on five mechanically ventilated pigs. RESULTS Optimal acceleration factor was fairly invariable (2.0–2.2×) over the range of simulated resolutions. Estimation accuracy progressively improved with higher resolutions (39–51% error reduction). In vivo r values were not significantly different between the two methods: 0.27±0.09, 0.35±0.06, 0.40±0.04 (standard) versus 0.23±0.05, 0.34±0.03, 0.37±0.02 (accelerated); for anterior, medial and posterior slices, respectively, whereas the corresponding vertical r gradients were significant (P < 0.001): 0.021±0.007 (standard) versus 0.019±0.005 (accelerated) [cm−1]. CONCLUSION Quadruple phased array coil simulations resulted in an optimal acceleration factor of ~2× independent of imaging resolution. Results advocate undersampled image acceleration to improve accuracy of fractional ventilation measurement with HP gas MRI. PMID:23400938

An investigation of two phase flow pressure drops in a reduced acceleration environment

NASA Astrophysics Data System (ADS)

Wheeler, Montgomery W.; Best, Frederick R.; Reinarts, Thomas R.

1993-01-01

Thermal systems for space applications based on two phase flow have several advantages over single phase systems. Two phase thermal energy management and dynamic power conversion system advantages include the capability of achieving high specific power levels. Before two phase systems for space applications can be designed effectively, knowledge of the flow behavior in a reduced acceleration environment is necessary. To meet these needs, two phase flow experiments were conducted aboard the National Aeronautic and Space Administration's KC-135 using R12 as the working fluid. Annular flow two phase pressure drops were measured through 10.41-mm ID 1.251-m long glass tubing during periods with acceleration levels in the range ±0.05 G. The experiments were conducted with emphasis on achieving data with a high level of accuracy. The reduced acceleration annular flow pressure drops were compred with pressure drops measured in a 1-G environment for similar flow conditions. The reduced acceleration pressure drops were found to be 45% greater than the 1-G pressure drops. In addition, the reduced acceleration annular flow interfacial friction factors were compared with models for vertical up-flow in a 1-G environment. The reduced acceleration interfacial friction factor data was not predicted by the 1-G models.

Physiological Effects of Acceleration Observed During a Centrifuge Study of Pilot Performance

NASA Technical Reports Server (NTRS)

Smedal, Harald A.; Creer, Brent Y.; Wingrove, Rodney C.

1960-01-01

An investigation was conducted by the National Aeronautics and Space Administration, Ames Research Center, and the Naval Air Development Center, Aviation Medical Acceleration Laboratory, to study the effects of acceleration on pilot performance and to obtain some meaningful data for use in establishing tolerance to acceleration levels. The flight simulator used in the study was the Johnsville centrifuge operated as a closed loop system. The pilot was required to perform a control task in various sustained acceleration fields typical of those that Might be encountered by a pilot flying an entry vehicle in which he is seated in a forward-facing position. A special restraint system was developed and designed to increase the pilot's tolerance to these accelerations. The results of this study demonstrated that a well-trained subject, such as a test pilot, can adequately carry out a control task during moderately high accelerations for prolonged periods of time. The maximum levels of acceleration tolerated were approximately 6 times that of gravity for approximately 6 minutes, and varied slightly with the acceleration direction. The tolerance runs were in each case terminated by the subject. In all but two instances, the cause was extreme fatigue. On two occasions the subject terminated the run when he "grayed out." Although there were subjective and objective findings involving the visual and cardiovascular systems, the respiratory system yielded the more critical limiting factors. It would appear that these limiting factors were less severe during the "eyeballs-out" accelerations when compared with the "eyeballs-in" accelerations. These findings are explained on the basis of the influence that the inertial forces of acceleration have on the mechanics of respiration. A condensed version of this report was presented at the Annual Meeting of the Aerospace Medical Association, Miami Beach, May 5-11, 1960, in a paper entitled "Ability of Pilots to Perform a Control Task in Various Sustained Acceleration Fields."

An examination of sudden acceleration

DOT National Transportation Integrated Search

1989-01-01

This report describes the results of a study to identify and evaluate factors which could potentially cause or contribute to the occurrence of "Sudden Acceleration Incidents" (SAI). SAI are defined in this report as unintended, unexpected, high-power...

Accelerating gradient improvement from hole-boring to light-sail stage using shape-tailored laser front

NASA Astrophysics Data System (ADS)

Wang, W. P.; Shen, B. F.; Xu, Z. Z.

2017-01-01

The accelerating gradient of a proton beam is a crucial factor for the stable radiation pressure acceleration, because quickly accelerating protons into the relativistic region may reduce the multidimensional instability grow to a certain extent. In this letter, a shape-tailored laser is designed to accelerate the protons in a controllable high accelerating gradient in theory. Finally, a proton beam in the gigaelectronvolt range with an energy spread of ˜2.4% is obtained in one-dimensional particle-in-cell simulations. With the future development of the high-intense laser, the ability to accelerate a high energy proton beam using a shape-tailored laser will be important for realistic proton applications, such as fast ignition for inertial confinement fusion, medical therapy, and proton imaging.

Integrated transcriptome sequencing and dynamic analysis reveal carbon source partitioning between terpenoid and oil accumulation in developing Lindera glauca fruits.

PubMed

Niu, Jun; Chen, Yinlei; An, Jiyong; Hou, Xinyu; Cai, Jian; Wang, Jia; Zhang, Zhixiang; Lin, Shanzhi

2015-10-08

Lindera glauca fruits (LGF) with the abundance of terpenoid and oil has emerged as a novel specific material for industrial and medicinal application in China, but the complex regulatory mechanisms of carbon source partitioning into terpenoid biosynthetic pathway (TBP) and oil biosynthetic pathway (OBP) in developing LGF is still unknown. Here we perform the analysis of contents and compositions of terpenoid and oil from 7 stages of developing LGF to characterize a dramatic difference in temporal accumulative patterns. The resulting 3 crucial samples at 50, 125 and 150 days after flowering (DAF) were selected for comparative deep transcriptome analysis. By Illumina sequencing, the obtained approximately 81 million reads are assembled into 69,160 unigenes, among which 174, 71, 81 and 155 unigenes are implicated in glycolysis, pentose phosphate pathway (PPP), TBP and OBP, respectively. Integrated differential expression profiling and qRT-PCR, we specifically characterize the key enzymes and transcription factors (TFs) involved in regulating carbon allocation ratios for terpenoid or oil accumulation in developing LGF. These results contribute to our understanding of the regulatory mechanisms of carbon source partitioning between terpenoid and oil in developing LGF, and to the improvement of resource utilization and molecular breeding for L. glauca.

Endogenous cGMP regulates adult longevity via the insulin signaling pathway in Caenorhabditis elegans.

PubMed

Hahm, Jeong-Hoon; Kim, Sunhee; Paik, Young-Ki

2009-08-01

G-proteins, including GPA-3, play an important role in regulating physiological responses in Caenorhabditis elegans. When confronted with an environmental stimulus such as dauer pheromone, or poor nutrients, C. elegans receives and integrates external signals through its nervous system (i.e. amphid neurons), which interprets and translates them into biological action. Here it is shown that a suppressed neuronal cGMP level caused by GPA-3 activation leads to a significant increase (47.3%) in the mean lifespan of adult C. elegans through forkhead transcription factor family O (FOXO)-mediated signal. A reduced neuronal cGMP level was found to be caused by an increased cGMP-specific phosphodiesterase activity at the transcriptional level. Our results using C. elegans mutants with specific deficits in TGF-beta and FOXO RNAi system suggest a mechanism in that cGMP, TGF-beta, and FOXO signaling interact to differentially produce the insulin-like molecules, ins-7 and daf-28, causing suppression of the insulin/IGF-1 pathway and promoting lifespan extension. Our findings provide not only a new mechanism of cGMP-mediated induction of longevity in adult C. elegans but also a possible therapeutic strategy for neuronal disease, which has been likened to brain diabetes.

A Cylindrical, Inner Volume Selecting 2D-T2-Prep Improves GRAPPA-Accelerated Image Quality in MRA of the Right Coronary Artery

PubMed Central

Coristine, Andrew J.; Yerly, Jerome; Stuber, Matthias

2016-01-01

Background Two-dimensional (2D) spatially selective radiofrequency (RF) pulses may be used to excite restricted volumes. By incorporating a "pencil beam" 2D pulse into a T2-Prep, one may create a "2D-T2-Prep" that combines T2-weighting with an intrinsic outer volume suppression. This may particularly benefit parallel imaging techniques, where artefacts typically originate from residual foldover signal. By suppressing foldover signal with a 2D-T2-Prep, image quality may therefore improve. We present numerical simulations, phantom and in vivo validations to address this hypothesis. Methods A 2D-T2-Prep and a conventional T2-Prep were used with GRAPPA-accelerated MRI (R = 1.6). The techniques were first compared in numerical phantoms, where per pixel maps of SNR (SNRmulti), noise, and g-factor were predicted for idealized sequences. Physical phantoms, with compartments doped to mimic blood, myocardium, fat, and coronary vasculature, were scanned with both T2-Preparation techniques to determine the actual SNRmulti and vessel sharpness. For in vivo experiments, the right coronary artery (RCA) was imaged in 10 healthy adults, using accelerations of R = 1,3, and 6, and vessel sharpness was measured for each. Results In both simulations and phantom experiments, the 2D-T2-Prep improved SNR relative to the conventional T2-Prep, by an amount that depended on both the acceleration factor and the degree of outer volume suppression. For in vivo images of the RCA, vessel sharpness improved most at higher acceleration factors, demonstrating that the 2D-T2-Prep especially benefits accelerated coronary MRA. Conclusion Suppressing outer volume signal with a 2D-T2-Prep improves image quality particularly well in GRAPPA-accelerated acquisitions in simulations, phantoms, and volunteers, demonstrating that it should be considered when performing accelerated coronary MRA. PMID:27736866

A human factors approach to snowsport safety: Novel research on pediatric participants' behaviors and head injury risk.

PubMed

Dickson, Tracey J; Trathen, Stephen; Waddington, Gordon; Terwiel, F Anne; Baltis, Daniel

2016-03-01

This study applied a human factors approach to snowsport resort systems to contribute to the understanding of the incidence and severity of pediatric snowsport head accelerations. Previous research indicates low magnitude head accelerations are common among snowsport participants. This study adds to the knowledge of snowsport safety by measuring aspects of participants' snowsport behavior and linking this with head acceleration data. School-aged students (n = 107) wore telemetry-fitted helmets and Global Positioning System (GPS) devices during snowsport activity. Data was collected over 159 sessions (total hours 701). Head accelerations recorded by the telemetry units were compared with GPS-generated data. This study found speeds attained normally exceed the testing rating for which helmets are designed; lower rates of head accelerations compared to earlier studies and that when head accelerations did occur they were generally below the threshold for concussions. Pediatric snowsport head accelerations are rare and are generally of low magnitude. Those most at risk of a head acceleration >40 g were male snowboarders. Given the recorded speeds in first time participants, increased targeting of novice snowsport participants to encourage education about the use of protective equipment, including helmets, is warranted. Post event recall was not a good indicator of having experienced a head impact. Consideration should be given to raising the standard design speed testing for snowsport helmet protective devices to reflect actual snowsport behaviors. Copyright © 2015 Elsevier Ltd and The Ergonomics Society. All rights reserved.

Do adverse pregnancy outcomes contribute to accelerated cardiovascular events seen in young women with systemic lupus erythematosus?

PubMed

Soh, M C; Nelson-Piercy, C; Westgren, M; McCowan, L; Pasupathy, D

2017-11-01

Cardiovascular events (CVEs) are prevalent in patients with systemic lupus erythematosus (SLE), and it is the young women who are disproportionately at risk. The risk factors for accelerated cardiovascular disease remain unclear, with multiple studies producing conflicting results. In this paper, we aim to address both traditional and SLE-specific risk factors postulated to drive the accelerated vascular disease in this cohort. We also discuss the more recent hypothesis that adverse pregnancy outcomes in the form of maternal-placental syndrome and resultant preterm delivery could potentially contribute to the CVEs seen in young women with SLE who have fewer traditional cardiovascular risk factors. The pathophysiology of how placental-mediated vascular insufficiency and hypoxia (with the secretion of placenta-like growth factor (PlGF) and soluble fms-tyrosine-like kinase-1 (sFlt-1), soluble endoglin (sEng) and other placental factors) work synergistically to damage the vascular endothelium is discussed. Adverse pregnancy outcomes ultimately are a small contributing factor to the complex pathophysiological process of cardiovascular disease in patients with SLE. Future collaborative studies between cardiologists, obstetricians, obstetric physicians and rheumatologists may pave the way for a better understanding of a likely multifactorial aetiological process.

Accelerated acquisition of tagged MRI for cardiac motion correction in simultaneous PET-MR: Phantom and patient studies

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

Huang, Chuan, E-mail: chuan.huang@stonybrookmedicine.edu; Department of Radiology, Harvard Medical School, Boston, Massachusetts 02115; Departments of Radiology, Psychiatry, Stony Brook Medicine, Stony Brook, New York 11794

2015-02-15

Purpose: Degradation of image quality caused by cardiac and respiratory motions hampers the diagnostic quality of cardiac PET. It has been shown that improved diagnostic accuracy of myocardial defect can be achieved by tagged MR (tMR) based PET motion correction using simultaneous PET-MR. However, one major hurdle for the adoption of tMR-based PET motion correction in the PET-MR routine is the long acquisition time needed for the collection of fully sampled tMR data. In this work, the authors propose an accelerated tMR acquisition strategy using parallel imaging and/or compressed sensing and assess the impact on the tMR-based motion corrected PETmore » using phantom and patient data. Methods: Fully sampled tMR data were acquired simultaneously with PET list-mode data on two simultaneous PET-MR scanners for a cardiac phantom and a patient. Parallel imaging and compressed sensing were retrospectively performed by GRAPPA and kt-FOCUSS algorithms with various acceleration factors. Motion fields were estimated using nonrigid B-spline image registration from both the accelerated and fully sampled tMR images. The motion fields were incorporated into a motion corrected ordered subset expectation maximization reconstruction algorithm with motion-dependent attenuation correction. Results: Although tMR acceleration introduced image artifacts into the tMR images for both phantom and patient data, motion corrected PET images yielded similar image quality as those obtained using the fully sampled tMR images for low to moderate acceleration factors (<4). Quantitative analysis of myocardial defect contrast over ten independent noise realizations showed similar results. It was further observed that although the image quality of the motion corrected PET images deteriorates for high acceleration factors, the images were still superior to the images reconstructed without motion correction. Conclusions: Accelerated tMR images obtained with more than 4 times acceleration can still provide relatively accurate motion fields and yield tMR-based motion corrected PET images with similar image quality as those reconstructed using fully sampled tMR data. The reduction of tMR acquisition time makes it more compatible with routine clinical cardiac PET-MR studies.« less

Factors influencing equipment selection in electron beam processing

NASA Astrophysics Data System (ADS)

Barnard, J. W.

2003-08-01

During the eighties and nineties accelerator manufacturers dramatically increased the beam power available for high-energy equipment. This effort was directed primarily at meeting the demands of the sterilization industry. During this era, the perception that bigger (higher power, higher energy) was always better prevailed since the operating and capital costs of accelerators did not increase with power and energy as fast as the throughput. High power was needed to maintain per unit costs low for treatment. This philosophy runs counter to certain present-day realities of the sterilization business as well as conditions influencing accelerator selection in other electron beam applications. Recent experience in machine selection is described and factors affecting choice are presented.

Particle Acceleration, Magnetic Field Generation, and Emission in Relativistic Pair Jets

NASA Technical Reports Server (NTRS)

Nishikawa, K. I.; Hardee, P.; Hededal, C. B.; Richardson, G.; Sol, H.; Preece, R.; Fishman, G. J.

2004-01-01

Shock acceleration is a ubiquitous phenomenon in astrophysical plasmas. Plasma waves and their associated instabilities (e.g., Buneman, Weibel and other two-stream instabilities) created in collisionless shocks are responsible for particle (electron, positron, and ion) acceleration. Using a 3-D relativistic electromagnetic particle (REMP) code, we have investigated particle acceleration associated with a relativistic jet front propagating into an ambient plasma. We find that the growth times depend on the Lorenz factors of jets. The jets with larger Lorenz factors grow slower. Simulations show that the Weibel instability created in the collisionless shock front accelerates jet and ambient particles both perpendicular and parallel to the jet propagation direction. The small scale magnetic field structure generated by the Weibel instability is appropriate to the generation of "jitter" radiation from deflected electrons (positrons) as opposed to synchrotron radiation. The jitter radiation resulting from small scale magnetic field structures may be important for understanding the complex time structure and spectral evolution observed in gamma-ray bursts or other astrophysical sources containing relativistic jets and relativistic collisionless shocks.

Accelerating policy decisions to adopt haemophilus influenzae type B vaccine: a global, multivariable analysis.

PubMed

Shearer, Jessica C; Stack, Meghan L; Richmond, Marcie R; Bear, Allyson P; Hajjeh, Rana A; Bishai, David M

2010-03-16

Adoption of new and underutilized vaccines by national immunization programs is an essential step towards reducing child mortality. Policy decisions to adopt new vaccines in high mortality countries often lag behind decisions in high-income countries. Using the case of Haemophilus influenzae type b (Hib) vaccine, this paper endeavors to explain these delays through the analysis of country-level economic, epidemiological, programmatic and policy-related factors, as well as the role of the Global Alliance for Vaccines and Immunisation (GAVI Alliance). Data for 147 countries from 1990 to 2007 were analyzed in accelerated failure time models to identify factors that are associated with the time to decision to adopt Hib vaccine. In multivariable models that control for Gross National Income, region, and burden of Hib disease, the receipt of GAVI support speeded the time to decision by a factor of 0.37 (95% CI 0.18-0.76), or 63%. The presence of two or more neighboring country adopters accelerated decisions to adopt by a factor of 0.50 (95% CI 0.33-0.75). For each 1% increase in vaccine price, decisions to adopt are delayed by a factor of 1.02 (95% CI 1.00-1.04). Global recommendations and local studies were not associated with time to decision. This study substantiates previous findings related to vaccine price and presents new evidence to suggest that GAVI eligibility is associated with accelerated decisions to adopt Hib vaccine. The influence of neighboring country decisions was also highly significant, suggesting that approaches to support the adoption of new vaccines should consider supply- and demand-side factors.

Parallel/Vector Integration Methods for Dynamical Astronomy

NASA Astrophysics Data System (ADS)

Fukushima, T.

Progress of parallel/vector computers has driven us to develop suitable numerical integrators utilizing their computational power to the full extent while being independent on the size of system to be integrated. Unfortunately, the parallel version of Runge-Kutta type integrators are known to be not so efficient. Recently we developed a parallel version of the extrapolation method (Ito and Fukushima 1997), which allows variable timesteps and still gives an acceleration factor of 3-4 for general problems. While the vector-mode usage of Picard-Chebyshev method (Fukushima 1997a, 1997b) will lead the acceleration factor of order of 1000 for smooth problems such as planetary/satellites orbit integration. The success of multiple-correction PECE mode of time-symmetric implicit Hermitian integrator (Kokubo 1998) seems to enlighten Milankar's so-called "pipelined predictor corrector method", which is expected to lead an acceleration factor of 3-4. We will review these directions and discuss future prospects.

Parallel MR Imaging with Accelerations Beyond the Number of Receiver Channels Using Real Image Reconstruction.

PubMed

Ji, Jim; Wright, Steven

2005-01-01

Parallel imaging using multiple phased-array coils and receiver channels has become an effective approach to high-speed magnetic resonance imaging (MRI). To obtain high spatiotemporal resolution, the k-space is subsampled and later interpolated using multiple channel data. Higher subsampling factors result in faster image acquisition. However, the subsampling factors are upper-bounded by the number of parallel channels. Phase constraints have been previously proposed to overcome this limitation with some success. In this paper, we demonstrate that in certain applications it is possible to obtain acceleration factors potentially up to twice the channel numbers by using a real image constraint. Data acquisition and processing methods to manipulate and estimate of the image phase information are presented for improving image reconstruction. In-vivo brain MRI experimental results show that accelerations up to 6 are feasible with 4-channel data.

The effects of SENSE on PROPELLER imaging.

PubMed

Chang, Yuchou; Pipe, James G; Karis, John P; Gibbs, Wende N; Zwart, Nicholas R; Schär, Michael

2015-12-01

To study how sensitivity encoding (SENSE) impacts periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) image quality, including signal-to-noise ratio (SNR), robustness to motion, precision of motion estimation, and image quality. Five volunteers were imaged by three sets of scans. A rapid method for generating the g-factor map was proposed and validated via Monte Carlo simulations. Sensitivity maps were extrapolated to increase the area over which SENSE can be performed and therefore enhance the robustness to head motion. The precision of motion estimation of PROPELLER blades that are unfolded with these sensitivity maps was investigated. An interleaved R-factor PROPELLER sequence was used to acquire data with similar amounts of motion with and without SENSE acceleration. Two neuroradiologists independently and blindly compared 214 image pairs. The proposed method of g-factor calculation was similar to that provided by the Monte Carlo methods. Extrapolation and rotation of the sensitivity maps allowed for continued robustness of SENSE unfolding in the presence of motion. SENSE-widened blades improved the precision of rotation and translation estimation. PROPELLER images with a SENSE factor of 3 outperformed the traditional PROPELLER images when reconstructing the same number of blades. SENSE not only accelerates PROPELLER but can also improve robustness and precision of head motion correction, which improves overall image quality even when SNR is lost due to acceleration. The reduction of SNR, as a penalty of acceleration, is characterized by the proposed g-factor method. © 2014 Wiley Periodicals, Inc.

Ultra-High Accelerating Gradients in Radio-Frequency Cryogenic Copper Structures

NASA Astrophysics Data System (ADS)

Cahill, Alexander David

Normal conducting radio-frequency (rf) particle accelerators have many applications, including colliders for high energy physics, high-intensity synchrotron light sources, non-destructive testing for security, and medical radiation therapy. In these applications, the accelerating gradient is an important parameter. Specifically for high energy physics, increasing the accelerating gradient extends the potential energy reach and is viewed as a way to mitigate their considerable cost. Furthermore, a gradient increase will enable for more compact and thus accessible free electron lasers (FELs). The major factor limiting larger accelerating gradients is vacuum rf breakdown. Basic physics of this phenomenon has been extensively studied over the last few decades. During which, the occurrence of rf breakdowns was shown to be probabilistic, and can be characterized by a breakdown rate. The current consensus is that vacuum rf breakdowns are caused by movements of crystal defects induced by periodic mechanical stress. The stress may be caused by pulsed surface heating and large electric fields. A compelling piece of evidence that supports this hypothesis is that accelerating structures constructed from harder materials exhibit larger accelerating gradients for similar breakdown rates. One possible method to increase sustained electric fields in copper cavities is to cool them to temperatures below 77 K, where the rf surface resistance and coefficient of thermal expansion decrease, while the yield strength (which correlates with hardness) and thermal conductivity increase. These changes in material properties at low temperature increases metal hardness and decreases the mechanical stress from exposure to rf electromagnetic fields. To test the validity of the improvement in breakdown rate, experiments were conducted with cryogenic accelerating cavities in the Accelerator Structure Test Area (ASTA) at SLAC National Accelerator Laboratory. A short 11.4 GHz standing wave accelerating structure was conditioned to an accelerating gradient of 250 MV/m at 45 K with 108 rf pulses. At gradients greater than 150 MV/m I observed a degradation in the intrinsic quality factor of the cavity, Q0. I developed a model for the change in Q0 using measured field emission currents and rf signals. I found that the Q 0 degradation is consistent with the rf power being absorbed by strong field emission currents accelerated inside the cavity. I measured rf breakdown rates for 45 K and found 2*10-4/pulse/meter when accounting for any change in Q0. These are the largest accelerating gradients for a structure with similar breakdown rates. The final chapter presents the design of an rf photoinjector electron source that uses the cryogenic normal conducting accelerator technology: the TOPGUN. With this cryogenic rf photoinjector, the beam brightness will increase by over an order of a magnitude when compared to the current photoinjector for the Linac Coherent Light Source (LCLS). When using the TOPGUN as the source for an X-ray Free Electron Laser, the higher brightness would allow for a decrease in the required length of the LCLS undulator by more than a factor of two.

Neurite sprouting and synapse deterioration in the aging Caenorhabditis elegans nervous system.

PubMed

Toth, Marton Lorant; Melentijevic, Ilija; Shah, Leena; Bhatia, Aatish; Lu, Kevin; Talwar, Amish; Naji, Haaris; Ibanez-Ventoso, Carolina; Ghose, Piya; Jevince, Angela; Xue, Jian; Herndon, Laura A; Bhanot, Gyan; Rongo, Chris; Hall, David H; Driscoll, Monica

2012-06-27

Caenorhabditis elegans is a powerful model for analysis of the conserved mechanisms that modulate healthy aging. In the aging nematode nervous system, neuronal death and/or detectable loss of processes are not readily apparent, but because dendrite restructuring and loss of synaptic integrity are hypothesized to contribute to human brain decline and dysfunction, we combined fluorescence microscopy and electron microscopy (EM) to screen at high resolution for nervous system changes. We report two major components of morphological change in the aging C. elegans nervous system: (1) accumulation of novel outgrowths from specific neurons, and (2) physical decline in synaptic integrity. Novel outgrowth phenotypes, including branching from the main dendrite or new growth from somata, appear at a high frequency in some aging neurons, but not all. Mitochondria are often associated with age-associated branch sites. Lowered insulin signaling confers some maintenance of ALM and PLM neuron structural integrity into old age, and both DAF-16/FOXO and heat shock factor transcription factor HSF-1 exert neuroprotective functions. hsf-1 can act cell autonomously in this capacity. EM evaluation in synapse-rich regions reveals a striking decline in synaptic vesicle numbers and a diminution of presynaptic density size. Interestingly, old animals that maintain locomotory prowess exhibit less synaptic decline than same-age decrepit animals, suggesting that synaptic integrity correlates with locomotory healthspan. Our data reveal similarities between the aging C. elegans nervous system and mammalian brain, suggesting conserved neuronal responses to age. Dissection of neuronal aging mechanisms in C. elegans may thus influence the development of brain healthspan-extending therapies.

Neurite Sprouting and Synapse Deterioration in the Aging C. elegans Nervous System

PubMed Central

Toth, Marton; Melentijevic, Ilija; Shah, Leena; Bhatia, Aatish; Lu, Kevin; Talwar, Amish; Naji, Haaris; Ibanez-Ventoso, Carolina; Ghose, Piya; Jevince, Angela; Xue, Jian; Herndon, Laura A.; Bhanot, Gyan; Rongo, Chris; Hall, David H

2012-01-01

C. elegans is a powerful model for analysis of the conserved mechanisms that modulate healthy aging. In the aging nematode nervous system, neuronal death and/or detectable loss of processes are not readily apparent, but because dendrite restructuring and loss of synaptic integrity are hypothesized to contribute to human brain decline and dysfunction, we combined fluorescence microscopy and electron microscopy (EM) to screen at high resolution for nervous system changes. We report two major components of morphological change in the aging C. elegans nervous system: 1) accumulation of novel outgrowths from specific neurons, and 2) physical decline in synaptic integrity. Novel outgrowth phenotypes, including branching from the main dendrite or new growth from somata, appear at a high frequency in some aging neurons, but not all. Mitochondria are often associated with age-associated branch sites. Lowered insulin signaling confers some maintenance of ALM and PLM neuron structural integrity into old age, and both DAF-16/FOXO and heat shock factor transcription factor HSF-1 exert neuroprotective functions. hsf-1 can act cell autonomously in this capacity. EM evaluation in synapse-rich regions reveals a striking decline in synaptic vesicle numbers and a dimunition of presynaptic density size. Interestingly, old animals that maintain locomotory prowess exhibit less synaptic decline than same-age decrepit animals, suggesting that synaptic integrity correlates with locomotory healthspan. Our data reveal similarities between the aging C. elegans nervous system and mammalian brain, suggesting conserved neuronal responses to age. Dissection of neuronal aging mechanisms in C. elegans may thus influence the development of brain healthspan-extending therapies. PMID:22745480

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

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

Dhondt, Ineke; Petyuk, Vladislav A.; Cai, Huaihan

2016-09-01

Cellular protein quality can be maintained by proteolytic elimination of damaged proteins and replacing them with newly synthesized copies, a process called protein turnover (Ward, 2000). Protein turnover rates have been estimated using SILAC (stable isotope labeling by amino acids in cell culture) in prokaryotes and eukaryotes. The last decade has witnessed a growing interest in the analysis of whole-organism proteome dynamics in metazoans using the same approach (Claydon and Beynon, 2012). In recent work, SILAC was applied to monitor protein synthesis throughout life in adult Caenorhabditis elegans (Vukoti et al., 2015) and to investigate food intake (Gomez-Amaro et al.,more » 2015« less

Vermittlungstechnik

NASA Astrophysics Data System (ADS)

Plaßmann, Wilfried

In einem vorhandenen Nachrichtennetz sorgt die Vermittlungstechnik dafür, dass Informationen zu jeder Zeit von einem beliebigen Zugangspunkt zu einem beliebigen anderen Zugangspunkt übertragen werden können. Der gesamte Vorgang wird mit Vermittlung bezeichnet. Das größte weltweit vorhandene Nachrichtennetz ist das kombinierte Internet-Telefonnetz. Die Zugangspunkte sind die Anschlusspunkte (ortsfeste Anschlussdosen) für die Endgeräte, wie z. B. Rechner, Telefonapparate, Faxgeräte oder Modems, oder aber ortsveränderliche Endgeräte wie Laptops, schnurlose Telefone oder Funktelefone ("Handys"). Die Vermittlungsstelle klassischer Art mit hierarchischem Aufbau ist nahezu vollständig durch komplexe rechnergesteuerte national arbeitende Anlagen ersetzt worden. In diesem Kapitel werden deshalb grundlegende Eigenschaften dargestellt. Stichworte: Grundbegriffe; Vermittlung; Verkehrstheorie; Endgeräte.

Open architecture design and approach for the Integrated Sensor Architecture (ISA)

NASA Astrophysics Data System (ADS)

Moulton, Christine L.; Krzywicki, Alan T.; Hepp, Jared J.; Harrell, John; Kogut, Michael

2015-05-01

Integrated Sensor Architecture (ISA) is designed in response to stovepiped integration approaches. The design, based on the principles of Service Oriented Architectures (SOA) and Open Architectures, addresses the problem of integration, and is not designed for specific sensors or systems. The use of SOA and Open Architecture approaches has led to a flexible, extensible architecture. Using these approaches, and supported with common data formats, open protocol specifications, and Department of Defense Architecture Framework (DoDAF) system architecture documents, an integration-focused architecture has been developed. ISA can help move the Department of Defense (DoD) from costly stovepipe solutions to a more cost-effective plug-and-play design to support interoperability.

Compressed sensing for rapid late gadolinium enhanced imaging of the left atrium: A preliminary study.

PubMed

Kamesh Iyer, Srikant; Tasdizen, Tolga; Burgon, Nathan; Kholmovski, Eugene; Marrouche, Nassir; Adluru, Ganesh; DiBella, Edward

2016-09-01

Current late gadolinium enhancement (LGE) imaging of left atrial (LA) scar or fibrosis is relatively slow and requires 5-15min to acquire an undersampled (R=1.7) 3D navigated dataset. The GeneRalized Autocalibrating Partially Parallel Acquisitions (GRAPPA) based parallel imaging method is the current clinical standard for accelerating 3D LGE imaging of the LA and permits an acceleration factor ~R=1.7. Two compressed sensing (CS) methods have been developed to achieve higher acceleration factors: a patch based collaborative filtering technique tested with acceleration factor R~3, and a technique that uses a 3D radial stack-of-stars acquisition pattern (R~1.8) with a 3D total variation constraint. The long reconstruction time of these CS methods makes them unwieldy to use, especially the patch based collaborative filtering technique. In addition, the effect of CS techniques on the quantification of percentage of scar/fibrosis is not known. We sought to develop a practical compressed sensing method for imaging the LA at high acceleration factors. In order to develop a clinically viable method with short reconstruction time, a Split Bregman (SB) reconstruction method with 3D total variation (TV) constraints was developed and implemented. The method was tested on 8 atrial fibrillation patients (4 pre-ablation and 4 post-ablation datasets). Blur metric, normalized mean squared error and peak signal to noise ratio were used as metrics to analyze the quality of the reconstructed images, Quantification of the extent of LGE was performed on the undersampled images and compared with the fully sampled images. Quantification of scar from post-ablation datasets and quantification of fibrosis from pre-ablation datasets showed that acceleration factors up to R~3.5 gave good 3D LGE images of the LA wall, using a 3D TV constraint and constrained SB methods. This corresponds to reducing the scan time by half, compared to currently used GRAPPA methods. Reconstruction of 3D LGE images using the SB method was over 20 times faster than standard gradient descent methods. Copyright © 2016 Elsevier Inc. All rights reserved.

Involvement of transcription factor encoded by the mouse mi locus (MITF) in apoptosis of cultured mast cells induced by removal of interleukin-3.

PubMed Central

Tsujimura, T.; Hashimoto, K.; Morii, E.; Tunio, G. M.; Tsujino, K.; Kondo, T.; Kanakura, Y.; Kitamura, Y.

1997-01-01

Mast cells develop when spleen cells of mice are cultured in the medium containing interleukin (IL)-3. Cultured mast cells (CMCs) show apoptosis when they are incubated in the medium without IL-3. We obtained CMCs from tg/tg mice that did not express the transcription factor encoded by the mi gene (MITF) due to the integration of a transgene at its 5' flanking region. MITF is a member of the basic-helix-loop-helix-leucine zipper (bHLH-Zip) protein family of transcription factors. We investigated the effect of MITF on the apoptosis of CMCs after removal of IL-3. When cDNA encoding normal MITF ((+)-MITF) was introduced into tg/tg CMCs with the retroviral vector, the apoptosis of tg/tg CMCs was significantly accelerated. The mutant mi allele represents a deletion of an arginine at the basic domain of MITF. The apoptosis of tg/tg CMCs was not accelerated by the introduction of cDNA encoding mi-MITF. The overexpression of (+)-MITF was not prerequisite to the acceleration of the apoptosis, as the apoptotic process proceeded faster in +/+ CMCs than in mi/mi CMCs. The Ba/F3 lymphoid cell line is also dependent on IL-3, and Ba/F3 cells show apoptosis after removal of IL-3. The c-myc gene encodes another transcription factor of the bHLH-Zip family, and the overexpression of the c-myc gene accelerated the apoptosis of Ba/F3 cells. However, the overexpression of (+)-MITF did not accelerate the apoptosis of Ba/F3 cells. The (+)-MITF appeared to play some roles for the acceleration of the apoptosis specifically in the mast cell lineage. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:9327738

Project acceleration : making the leap from pilot to commercialization.

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

Borneo, Daniel R.

2010-05-01

Since the energy storage technology market is in a relatively emergent phase, narrowing the gap between pilot project status and commercialization is fundamental to the accelerating of this innovative market space. This session will explore regional market design factors to facilitate the storage enterprise. You will also hear about: quantifying transmission and generation efficiency enhancements; resource planning for storage; and assessing market mechanisms to accelerate storage adoption regionally.

Aggregation factor analysis for protein formulation by a systematic approach using FTIR, SEC and design of experiments techniques.

PubMed

Feng, Yan Wen; Ooishi, Ayako; Honda, Shinya

2012-01-05

A simple systematic approach using Fourier transform infrared (FTIR) spectroscopy, size exclusion chromatography (SEC) and design of experiments (DOE) techniques was applied to the analysis of aggregation factors for protein formulations in stress and accelerated testings. FTIR and SEC were used to evaluate protein conformational and storage stabilities, respectively. DOE was used to determine the suitable formulation and to analyze both the main effect of single factors and the interaction effect of combined factors on aggregation. Our results indicated that (i) analysis at a low protein concentration is not always applicable to high concentration formulations; (ii) an investigation of interaction effects of combined factors as well as main effects of single factors is effective for improving conformational stability of proteins; (iii) with the exception of pH, the results of stress testing with regard to aggregation factors would be available for suitable formulation instead of performing time-consuming accelerated testing; (iv) a suitable pH condition should not be determined in stress testing but in accelerated testing, because of inconsistent effects of pH on conformational and storage stabilities. In summary, we propose a three-step strategy, using FTIR, SEC and DOE techniques, to effectively analyze the aggregation factors and perform a rapid screening for suitable conditions of protein formulation. Copyright © 2011 Elsevier B.V. All rights reserved.

Homo sapiens-Specific Binding Site Variants within Brain Exclusive Enhancers Are Subject to Accelerated Divergence across Human Population.

PubMed

Zehra, Rabail; Abbasi, Amir Ali

2018-03-01

Empirical assessments of human accelerated noncoding DNA frgaments have delineated presence of many cis-regulatory elements. Enhancers make up an important category of such accelerated cis-regulatory elements that efficiently control the spatiotemporal expression of many developmental genes. Establishing plausible reasons for accelerated enhancer sequence divergence in Homo sapiens has been termed significant in various previously published studies. This acceleration by including closely related primates and archaic human data has the potential to open up evolutionary avenues for deducing present-day brain structure. This study relied on empirically confirmed brain exclusive enhancers to avoid any misjudgments about their regulatory status and categorized among them a subset of enhancers with an exceptionally accelerated rate of lineage specific divergence in humans. In this assorted set, 13 distinct transcription factor binding sites were located that possessed unique existence in humans. Three of 13 such sites belonging to transcription factors SOX2, RUNX1/3, and FOS/JUND possessed single nucleotide variants that made them unique to H. sapiens upon comparisons with Neandertal and Denisovan orthologous sequences. These variants modifying the binding sites in modern human lineage were further substantiated as single nucleotide polymorphisms via exploiting 1000 Genomes Project Phase3 data. Long range haplotype based tests laid out evidence of positive selection to be governing in African population on two of the modern human motif modifying alleles with strongest results for SOX2 binding site. In sum, our study acknowledges acceleration in noncoding regulatory landscape of the genome and highlights functional parts within it to have undergone accelerated divergence in present-day human population.

Adult student satisfaction in an accelerated RN-to-BSN program: a follow-up study.

PubMed

Boylston, Mary T; Jackson, Christina

2008-01-01

This mixed-method study revealed accelerated RN-to-BSN (bachelor of science in nursing) students' levels of satisfaction with a wide range of college services in a small university. Building on seminal research on the topic [Boylston, M. T., Peters, M. A., & Lacey, M. (2004). Adult student satisfaction in traditional and accelerated RN-to-BSN programs. Journal of Professional Nursing, 20, 23-32.], the Noel-Levitz Adult Student Priorities Survey (ASPS) and qualitative interview data revealed primary factors involved in nontraditional (adult) accelerated RN-to-BSN student satisfaction. The ASPS assesses both satisfaction with and importance of the following factors: academic advising effectiveness, academic services, admissions and financial aid effectiveness, campus climate, instructional effectiveness, registration effectiveness, safety and security, and service excellence. Of these factors, participants considered instructional effectiveness and academic advising effectiveness as most important and concomitantly gave high satisfaction ratings to each. In contrast, convenience of the bookstore, counseling services, vending machines, and computer laboratories were given low importance ratings. The participants cited convenience as a strong marketing factor. Loss of financial aid or family crisis was given as a reason for withdrawal and, for most students, would be the only reason for not completing the BSN program. Outcomes of this investigation may guide faculty, staff, and administrators in proactively creating an educational environment in which a nontraditional student can succeed.

A 128-channel receive-only cardiac coil for highly accelerated cardiac MRI at 3 Tesla.

PubMed

Schmitt, Melanie; Potthast, Andreas; Sosnovik, David E; Polimeni, Jonathan R; Wiggins, Graham C; Triantafyllou, Christina; Wald, Lawrence L

2008-06-01

A 128-channel receive-only array coil is described and tested for cardiac imaging at 3T. The coil is closely contoured to the body with a "clam-shell" geometry with 68 posterior and 60 anterior elements, each 75 mm in diameter, and arranged in a continuous overlapped array of hexagonal symmetry to minimize nearest neighbor coupling. Signal-to-noise ratio (SNR) and noise amplification for parallel imaging (G-factor) were evaluated in phantom and volunteer experiments. These results were compared to those of commercially available 24-channel and 32-channel coils in routine use for cardiac imaging. The in vivo measurements with the 128-channel coil resulted in SNR gains compared to the 24-channel coil (up to 2.2-fold in the apex). The 128- and 32-channel coils showed similar SNR in the heart, likely dominated by the similar element diameters of these coils. The maximum G-factor values were up to seven times better for a seven-fold acceleration factor (R=7) compared to the 24-channel coil and up to two-fold improved compared to the 32-channel coil. The ability of the 128-channel coil to facilitate highly accelerated cardiac imaging was demonstrated in four volunteers using acceleration factors up to seven-fold (R=7) in a single spatial dimension. Copyright (c) 2008 Wiley-Liss, Inc.

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

PubMed

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 venous. Total or partial liver transplants have been performed with success in these patients and have "cured" their deficiencies. Prenatal diagnosis has also been performed and recent research involves the development of inhibitors of FVII + tissue factor complex or of FVIIa. This approach, if successful, could provide another antithrombotic therapeutics tool. The story of FVII well summarizes the efforts of both theoretical and clinical approaches in the characterization of a coagulation disorder, that is, among the rare bleeding conditions, most frequently encountered in clinical practice. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.