Sample records for activity-modifying proteins ramps

  1. Pharmacological characterization of receptor-activity-modifying proteins (RAMPs) and the human calcitonin receptor.

    PubMed

    Armour, S L; Foord, S; Kenakin, T; Chen, W J

    1999-12-01

    Receptor-activity-modifying proteins (RAMPs) are a family of single transmembrane domain proteins shown to be important for the transport and ligand specificity of the calcitonin gene-related peptide (CGRP) receptor. In this report, we describe the analysis of pharmacological properties of the human calcitonin receptor (hCTR) coexpressed with different RAMPs with the use of the Xenopus laevis melanophore expression system. We show that coexpression of RAMP3 with human calcitonin receptor changed the relative potency of hCTR to human calcitonin (hCAL) and rat amylin. RAMP1 and RAMP2, in contrast, had little effect on the change of hCTR potency to hCAL or rat amylin. When coexpressed with RAMP3, hCTR reversed the relative potency by a 3.5-fold loss in sensitivity to hCAL and a 19-fold increase in sensitivity to rat amylin. AC66, an inverse agonist, produced apparent simple competitive antagonism of hCAL and rat amylin, as indicated by linear Schild regressions. The potency of AC66 was changed in the blockade of rat amylin but not hCAL responses with RAMP3 coexpression. The mean pK(B) for AC66 to hCAL was 9.4 +/- 0.3 without RAMP3 and 9.45 +/- 0.07 with RAMP3. For the antagonism of AC66 to rat amylin, the pK(B) was 9.25 +/- 0.15 without RAMP3 and 8.2 +/- 0.35 with RAMP3. The finding suggests that RAMP3 might modify the active states of calcitonin receptor in such a way as to create a new receptor phenotype that is "amylin-like." Irrespective of the physiological association of the new receptor species, the finding that a coexpressed membrane protein can completely change agonist and antagonist affinities for a receptor raises implications for screening in recombinant receptor systems.

  2. Functional relevance of G-protein-coupled-receptor-associated proteins, exemplified by receptor-activity-modifying proteins (RAMPs).

    PubMed

    Fischer, J A; Muff, R; Born, W

    2002-08-01

    The calcitonin (CT) receptor (CTR) and the CTR-like receptor (CRLR) are close relatives within the type II family of G-protein-coupled receptors, demonstrating sequence identity of 50%. Unlike the interaction between CT and CTR, receptors for the related hormones and neuropeptides amylin, CT-gene-related peptide (CGRP) and adrenomedullin (AM) require one of three accessory receptor-activity-modifying proteins (RAMPs) for ligand recognition. An amylin/CGRP receptor is revealed when CTR is co-expressed with RAMP1. When complexed with RAMP3, CTR interacts with amylin alone. CRLR, initially classed as an orphan receptor, is a CGRP receptor when co-expressed with RAMP1. The same receptor is specific for AM in the presence of RAMP2. Together with human RAMP3, CRLR defines an AM receptor, and with mouse RAMP3 it is a low-affinity CGRP/AM receptor. CTR-RAMP1, antagonized preferentially by salmon CT-(8-32) and not by CGRP-(8-37), and CRLR-RAMP1, antagonized by CGRP-(8-37), are two CGRP receptor isotypes. Thus amylin and CGRP interact specifically with heterodimeric complexes between CTR and RAMP1 or RAMP3, and CGRP and AM interact with complexes between CRLR and RAMP1, RAMP2 or RAMP3.

  3. LOCALIZATION OF CALCITONIN RECEPTOR-LIKE RECEPTOR (CLR) AND RECEPTOR ACTIVITY-MODIFYING PROTEIN 1 (RAMP1) IN HUMAN GASTROINTESTINAL TRACT

    PubMed Central

    Cottrell, Graeme S.; Alemi, Farzad; Kirkland, Jacob G.; Grady, Eileen F.; Corvera, Carlos U.; Bhargava, Aditi

    2012-01-01

    Calcitonin gene-related peptide (CGRP) exerts its diverse effects on vasodilation, nociception, secretion, and motor function through a heterodimeric receptor comprising of calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1). Despite the importance of CLR•RAMP1 in human disease, little is known about its distribution in the human gastrointestinal (GI) tract, where it participates in inflammation and pain. In this study, we determined that CLR and RAMP1 mRNAs are expressed in normal human stomach, ileum and colon by RT-PCR. We next characterized antibodies that we generated to rat CLR and RAMP1 in transfected HEK cells. Having characterized these antibodies in vitro, we then localized CLR-, RAMP1-, CGRP- and intermedin-immunoreactivity (IMD-IR) in various human GI segments. In the stomach, nerve bundles in the myenteric plexus and nerve fibers throughout the circular and longitudinal muscle had prominent CLR-IR. In the proximal colon and ileum, CLR was found in nerve varicosities of the myenteric plexus and surrounding submucosal neurons. Interestingly, CGRP expressing fibers did not co-localize, but were in close proximity to CLR. However, CLR and RAMP1, the two subunits of a functional CGRP receptor were clearly localized in myenteric plexus, where they may form functional cell-surface receptors. IMD, another member of calcitonin peptide family was also found in close proximity to CLR, and like CGRP, did not co-localize with either CLR or RAMP1 receptors. Thus, CGRP and IMD appear to be released locally, where they can mediate their effect on their receptors regulating diverse functions such as inflammation, pain and motility. PMID:22484227

  4. Receptor Activity-modifying Protein-directed G Protein Signaling Specificity for the Calcitonin Gene-related Peptide Family of Receptors.

    PubMed

    Weston, Cathryn; Winfield, Ian; Harris, Matthew; Hodgson, Rose; Shah, Archna; Dowell, Simon J; Mobarec, Juan Carlos; Woodlock, David A; Reynolds, Christopher A; Poyner, David R; Watkins, Harriet A; Ladds, Graham

    2016-10-14

    The calcitonin gene-related peptide (CGRP) family of G protein-coupled receptors (GPCRs) is formed through the association of the calcitonin receptor-like receptor (CLR) and one of three receptor activity-modifying proteins (RAMPs). Binding of one of the three peptide ligands, CGRP, adrenomedullin (AM), and intermedin/adrenomedullin 2 (AM2), is well known to result in a Gα s -mediated increase in cAMP. Here we used modified yeast strains that couple receptor activation to cell growth, via chimeric yeast/Gα subunits, and HEK-293 cells to characterize the effect of different RAMP and ligand combinations on this pathway. We not only demonstrate functional couplings to both Gα s and Gα q but also identify a Gα i component to CLR signaling in both yeast and HEK-293 cells, which is absent in HEK-293S cells. We show that the CGRP family of receptors displays both ligand- and RAMP-dependent signaling bias among the Gα s , Gα i , and Gα q/11 pathways. The results are discussed in the context of RAMP interactions probed through molecular modeling and molecular dynamics simulations of the RAMP-GPCR-G protein complexes. This study further highlights the importance of RAMPs to CLR pharmacology and to bias in general, as well as identifying the importance of choosing an appropriate model system for the study of GPCR pharmacology. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. Structural basis for receptor activity-modifying protein-dependent selective peptide recognition by a G protein-coupled receptor

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

    Booe, Jason M.; Walker, Christopher S.; Barwell, James

    Association of receptor activity-modifying proteins (RAMP1-3) with the G protein-coupled receptor (GPCR) calcitonin receptor-like receptor (CLR) enables selective recognition of the peptides calcitonin gene-related peptide (CGRP) and adrenomedullin (AM) that have diverse functions in the cardiovascular and lymphatic systems. How peptides selectively bind GPCR:RAMP complexes is unknown. We report crystal structures of CGRP analog-bound CLR:RAMP1 and AM-bound CLR:RAMP2 extracellular domain heterodimers at 2.5 and 1.8 Å resolutions, respectively. The peptides similarly occupy a shared binding site on CLR with conformations characterized by a β-turn structure near their C termini rather than the α-helical structure common to peptides that bind relatedmore » GPCRs. The RAMPs augment the binding site with distinct contacts to the variable C-terminal peptide residues and elicit subtly different CLR conformations. Lastly, the structures and accompanying pharmacology data reveal how a class of accessory membrane proteins modulate ligand binding of a GPCR and may inform drug development targeting CLR:RAMP complexes.« less

  6. Structural basis for receptor activity-modifying protein-dependent selective peptide recognition by a G protein-coupled receptor

    DOE PAGES

    Booe, Jason M.; Walker, Christopher S.; Barwell, James; ...

    2015-05-14

    Association of receptor activity-modifying proteins (RAMP1-3) with the G protein-coupled receptor (GPCR) calcitonin receptor-like receptor (CLR) enables selective recognition of the peptides calcitonin gene-related peptide (CGRP) and adrenomedullin (AM) that have diverse functions in the cardiovascular and lymphatic systems. How peptides selectively bind GPCR:RAMP complexes is unknown. We report crystal structures of CGRP analog-bound CLR:RAMP1 and AM-bound CLR:RAMP2 extracellular domain heterodimers at 2.5 and 1.8 Å resolutions, respectively. The peptides similarly occupy a shared binding site on CLR with conformations characterized by a β-turn structure near their C termini rather than the α-helical structure common to peptides that bind relatedmore » GPCRs. The RAMPs augment the binding site with distinct contacts to the variable C-terminal peptide residues and elicit subtly different CLR conformations. Lastly, the structures and accompanying pharmacology data reveal how a class of accessory membrane proteins modulate ligand binding of a GPCR and may inform drug development targeting CLR:RAMP complexes.« less

  7. Is the activity of CGRP and Adrenomedullin regulated by RAMP (-2) and (-3) in Trypanosomatidae? An in-silico approach.

    PubMed

    Febres, Anthony; Vanegas, Oriana; Giammarresi, Michelle; Gomes, Carlos; Díaz, Emilia; Ponte-Sucre, Alicia

    2018-07-01

    The Calcitonin-Like Receptor (CLR) belongs to the classical seven-transmembrane segment molecules coupled to heterotrimeric G proteins. Its pharmacology depends on the simultaneous expression of the so-called Receptor Activity Modifier Proteins (RAMP-) -1, -2 and -3. RAMP-associated proteins modulate glycosylation and cellular traffic of CLR, therefore determining its pharmacodynamics. In higher eukaryotes, the complex formed by CLR and RAMP-1 is more akin to bind Calcitonin Gene-Related Peptide (CGRP), whereas those formed by CLR and RAMP-2 or RAMP-3, bind preferentially Adrenomedullin (AM). In lower eukaryotes, RAMPs, or any homologous protein, have not been identified until now. Herein we demonstrated a negative chemotactic response elicited by CGRP (10 -9 and 10 -8  M) and AM (10 -9 to 10 -5  M). Whether or not this response is receptor mediated should be verified, as well as the expression of a 24 kDa band in Leishmania, recognized by western blot analysis by the use of (human-)-RAMP-2 antibodies as detection probes. Queries with human RAMP-2 and RAMP-3 protein sequences in blastp against Leishmania (Viannia) braziliensis predicted proteome, allowed us to detect two sequence alignments in the parasite: A RAMP-2-aligned sequence corresponding to Leishmania folylpolyglutamate synthase (FPGS), and a RAMP-3 aligned protein, a hypothetical Leishmania protein with yet unknown function. The presence of homologous of these proteins was described in-silico in other members of the Trypanosomatidae. These preliminary and not yet complete data suggest the feasibility that both CGRP and Adrenomedullin activities may be regulated by homologs of RAMP- (-2) and (-3) in these parasites. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. RAMP2 Influences Glucagon Receptor Pharmacology via Trafficking and Signaling.

    PubMed

    Cegla, Jaimini; Jones, Ben J; Gardiner, James V; Hodson, David J; Marjot, Thomas; McGlone, Emma R; Tan, Tricia M; Bloom, Stephen R

    2017-08-01

    Endogenous satiety hormones provide an attractive target for obesity drugs. Glucagon causes weight loss by reducing food intake and increasing energy expenditure. To further understand the cellular mechanisms by which glucagon and related ligands activate the glucagon receptor (GCGR), we investigated the interaction of the GCGR with receptor activity modifying protein (RAMP)2, a member of the family of receptor activity modifying proteins. We used a combination of competition binding experiments, cell surface enzyme-linked immunosorbent assay, functional assays assessing the Gαs and Gαq pathways and β-arrestin recruitment, and small interfering RNA knockdown to examine the effect of RAMP2 on the GCGR. Ligands tested were glucagon; glucagonlike peptide-1 (GLP-1); oxyntomodulin; and analog G(X), a GLP-1/glucagon coagonist developed in-house. Confocal microscopy was used to assess whether RAMP2 affects the subcellular distribution of GCGR. Here we demonstrate that coexpression of RAMP2 and the GCGR results in reduced cell surface expression of the GCGR. This was confirmed by confocal microscopy, which demonstrated that RAMP2 colocalizes with the GCGR and causes significant GCGR cellular redistribution. Furthermore, the presence of RAMP2 influences signaling through the Gαs and Gαq pathways, as well as recruitment of β-arrestin. This work suggests that RAMP2 may modify the agonist activity and trafficking of the GCGR, with potential relevance to production of new peptide analogs with selective agonist activities.

  9. Calcitonin and Amylin Receptor Peptide Interaction Mechanisms: INSIGHTS INTO PEPTIDE-BINDING MODES AND ALLOSTERIC MODULATION OF THE CALCITONIN RECEPTOR BY RECEPTOR ACTIVITY-MODIFYING PROTEINS.

    PubMed

    Lee, Sang-Min; Hay, Debbie L; Pioszak, Augen A

    2016-04-15

    Receptor activity-modifying proteins (RAMP1-3) determine the selectivity of the class B G protein-coupled calcitonin receptor (CTR) and the CTR-like receptor (CLR) for calcitonin (CT), amylin (Amy), calcitonin gene-related peptide (CGRP), and adrenomedullin (AM) peptides. RAMP1/2 alter CLR selectivity for CGRP/AM in part by RAMP1 Trp-84 or RAMP2 Glu-101 contacting the distinct CGRP/AM C-terminal residues. It is unclear whether RAMPs use a similar mechanism to modulate CTR affinity for CT and Amy, analogs of which are therapeutics for bone disorders and diabetes, respectively. Here, we reproduced the peptide selectivity of intact CTR, AMY1 (CTR·RAMP1), and AMY2 (CTR·RAMP2) receptors using purified CTR extracellular domain (ECD) and tethered RAMP1- and RAMP2-CTR ECD fusion proteins and antagonist peptides. All three proteins bound salmon calcitonin (sCT). Tethering RAMPs to CTR enhanced binding of rAmy, CGRP, and the AMY antagonist AC413. Peptide alanine-scanning mutagenesis and modeling of receptor-bound sCT and AC413 supported a shared non-helical CGRP-like conformation for their TN(T/V)G motif prior to the C terminus. After this motif, the peptides diverged; the sCT C-terminal Pro was crucial for receptor binding, whereas the AC413/rAmy C-terminal Tyr had little or no influence on binding. Accordingly, mutant RAMP1 W84A- and RAMP2 E101A-CTR ECD retained AC413/rAmy binding. ECD binding and cell-based signaling assays with antagonist sCT/AC413/rAmy variants with C-terminal residue swaps indicated that the C-terminal sCT/rAmy residue identity affects affinity more than selectivity. rAmy(8-37) Y37P exhibited enhanced antagonism of AMY1 while retaining selectivity. These results reveal unexpected differences in how RAMPs determine CTR and CLR peptide selectivity and support the hypothesis that RAMPs allosterically modulate CTR peptide affinity. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Receptor activity-modifying protein-dependent effects of mutations in the calcitonin receptor-like receptor: implications for adrenomedullin and calcitonin gene-related peptide pharmacology

    PubMed Central

    Watkins, H A; Walker, C S; Ly, K N; Bailey, R J; Barwell, J; Poyner, D R; Hay, D L

    2014-01-01

    Background and Purpose Receptor activity-modifying proteins (RAMPs) define the pharmacology of the calcitonin receptor-like receptor (CLR). The interactions of the different RAMPs with this class B GPCR yield high-affinity calcitonin gene-related peptide (CGRP) or adrenomedullin (AM) receptors. However, the mechanism for this is unclear. Experimental Approach Guided by receptor models, we mutated residues in the N-terminal helix of CLR, RAMP2 and RAMP3 hypothesized to be involved in peptide interactions. These were assayed for cAMP production with AM, AM2 and CGRP together with their cell surface expression. Binding studies were also conducted for selected mutants. Key Results An important domain for peptide interactions on CLR from I32 to I52 was defined. Although I41 was universally important for binding and receptor function, the role of other residues depended on both ligand and RAMP. Peptide binding to CLR/RAMP3 involved a more restricted range of residues than that to CLR/RAMP1 or CLR/RAMP2. E101 of RAMP2 had a major role in AM interactions, and F111/W84 of RAMP2/3 was important with each peptide. Conclusions and Implications RAMP-dependent effects of CLR mutations suggest that the different RAMPs control accessibility of peptides to binding residues situated on the CLR N-terminus. RAMP3 appears to alter the role of specific residues at the CLR-RAMP interface compared with RAMP1 and RAMP2. PMID:24199627

  11. Role of Receptor Activity Modifying Protein 1 in Function of the Calcium Sensing Receptor in the Human TT Thyroid Carcinoma Cell Line

    PubMed Central

    Desai, Aditya J.; Roberts, David J.

    2014-01-01

    The Calcium Sensing Receptor (CaSR) plays a role in calcium homeostasis by sensing minute changes in serum Ca2+ and modulating secretion of calciotropic hormones. It has been shown in transfected cells that accessory proteins known as Receptor Activity Modifying Proteins (RAMPs), specifically RAMPs 1 and 3, are required for cell-surface trafficking of the CaSR. These effects have only been demonstrated in transfected cells, so their physiological relevance is unclear. Here we explored CaSR/RAMP interactions in detail, and showed that in thyroid human carcinoma cells, RAMP1 is required for trafficking of the CaSR. Furthermore, we show that normal RAMP1 function is required for intracellular responses to ligands. Specifically, to confirm earlier studies with tagged constructs, and to provide the additional benefit of quantitative stoichiometric analysis, we used fluorescence resonance energy transfer to show equal abilities of RAMP1 and 3 to chaperone CaSR to the cell surface, though RAMP3 interacted more efficiently with the receptor. Furthermore, a higher fraction of RAMP3 than RAMP1 was observed in CaSR-complexes on the cell-surface, suggesting different ratios of RAMPs to CaSR. In order to determine relevance of these findings in an endogenous expression system we assessed the effect of RAMP1 siRNA knock-down in medullary thyroid carcinoma TT cells, (which express RAMP1, but not RAMP3 constitutively) and measured a significant 50% attenuation of signalling in response to CaSR ligands Cinacalcet and neomycin. Blockade of RAMP1 using specific antibodies induced a concentration-dependent reduction in CaSR-mediated signalling in response to Cinacalcet in TT cells, suggesting a novel functional role for RAMP1 in regulation of CaSR signalling in addition to its known role in receptor trafficking. These data provide evidence that RAMPs traffic the CaSR as higher-level oligomers and play a role in CaSR signalling even after cell surface localisation has occurred. PMID

  12. Role of receptor activity modifying protein 1 in function of the calcium sensing receptor in the human TT thyroid carcinoma cell line.

    PubMed

    Desai, Aditya J; Roberts, David J; Richards, Gareth O; Skerry, Timothy M

    2014-01-01

    The Calcium Sensing Receptor (CaSR) plays a role in calcium homeostasis by sensing minute changes in serum Ca(2+) and modulating secretion of calciotropic hormones. It has been shown in transfected cells that accessory proteins known as Receptor Activity Modifying Proteins (RAMPs), specifically RAMPs 1 and 3, are required for cell-surface trafficking of the CaSR. These effects have only been demonstrated in transfected cells, so their physiological relevance is unclear. Here we explored CaSR/RAMP interactions in detail, and showed that in thyroid human carcinoma cells, RAMP1 is required for trafficking of the CaSR. Furthermore, we show that normal RAMP1 function is required for intracellular responses to ligands. Specifically, to confirm earlier studies with tagged constructs, and to provide the additional benefit of quantitative stoichiometric analysis, we used fluorescence resonance energy transfer to show equal abilities of RAMP1 and 3 to chaperone CaSR to the cell surface, though RAMP3 interacted more efficiently with the receptor. Furthermore, a higher fraction of RAMP3 than RAMP1 was observed in CaSR-complexes on the cell-surface, suggesting different ratios of RAMPs to CaSR. In order to determine relevance of these findings in an endogenous expression system we assessed the effect of RAMP1 siRNA knock-down in medullary thyroid carcinoma TT cells, (which express RAMP1, but not RAMP3 constitutively) and measured a significant 50% attenuation of signalling in response to CaSR ligands Cinacalcet and neomycin. Blockade of RAMP1 using specific antibodies induced a concentration-dependent reduction in CaSR-mediated signalling in response to Cinacalcet in TT cells, suggesting a novel functional role for RAMP1 in regulation of CaSR signalling in addition to its known role in receptor trafficking. These data provide evidence that RAMPs traffic the CaSR as higher-level oligomers and play a role in CaSR signalling even after cell surface localisation has occurred.

  13. Wind Power Ramping Product for Increasing Power System Flexibility

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

    Cui, Mingjian; Zhang, Jie; Wu, Hongyu

    With increasing penetrations of wind power, system operators are concerned about a potential lack of system flexibility and ramping capacity in real-time dispatch stages. In this paper, a modified dispatch formulation is proposed considering the wind power ramping product (WPRP). A swinging door algorithm (SDA) and dynamic programming are combined and used to detect WPRPs in the next scheduling periods. The detected WPRPs are included in the unit commitment (UC) formulation considering ramping capacity limits, active power limits, and flexible ramping requirements. The modified formulation is solved by mixed integer linear programming. Numerical simulations on a modified PJM 5-bus Systemmore » show the effectiveness of the model considering WPRP, which not only reduces the production cost but also does not affect the generation schedules of thermal units.« less

  14. Function of the cytoplasmic tail of human calcitonin receptor-like receptor in complex with receptor activity-modifying protein 2

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

    Kuwasako, Kenji, E-mail: kuwasako@fc.miyazaki-u.ac.jp; Kitamura, Kazuo; Nagata, Sayaka

    2010-02-12

    Receptor activity-modifying protein 2 (RAMP2) enables calcitonin receptor-like receptor (CRLR) to form an adrenomedullin (AM)-specific receptor. Here we investigated the function of the cytoplasmic C-terminal tail (C-tail) of human (h)CRLR by co-transfecting its C-terminal mutants into HEK-293 cells stably expressing hRAMP2. Deleting the C-tail from CRLR disrupted AM-evoked cAMP production or receptor internalization, but did not affect [{sup 125}I]AM binding. We found that CRLR residues 428-439 are required for AM-evoked cAMP production, though deleting this region had little effect on receptor internalization. Moreover, pretreatment with pertussis toxin (100 ng/mL) led to significant increases in AM-induced cAMP production via wild-type CRLR/RAMP2more » complexes. This effect was canceled by deleting CRLR residues 454-457, suggesting Gi couples to this region. Flow cytometric analysis revealed that CRLR truncation mutants lacking residues in the Ser/Thr-rich region extending from Ser{sup 449} to Ser{sup 467} were unable to undergo AM-induced receptor internalization and, in contrast to the effect on wild-type CRLR, overexpression of GPCR kinases-2, -3 and -4 failed to promote internalization of CRLR mutants lacking residues 449-467. Thus, the hCRLR C-tail is crucial for AM-evoked cAMP production and internalization of the CRLR/RAMP2, while the receptor internalization is dependent on the aforementioned GPCR kinases, but not Gs coupling.« less

  15. Successful lyophilization by adopting a fast ramp rate during primary drying in protein formulations.

    PubMed

    Ohori, Ryo; Akita, Tomomi; Yamashita, Chikamasa

    2018-06-15

    In the lyophilization process for injections, the shelf temperature (T s ) and chamber pressure (P c ) have mainly been investigated to optimize the primary drying process. The objective of this study was to show that lyophilization of protein formulations can be achieved by adopting a fast ramp rate of T s in the beginning of the primary drying process. Bovine serum albumin was used as the model protein, and seven different lyophilized formulations obtained were stored at elevated temperature. We found that although acceptable cake appearance was confirmed by the fast ramp cycle, all formulations of lyophilized cakes obtained by the slow ramp cycle severely collapsed (macrocollapse). It is thought that the collapse in the slow ramp cycle occurred during the shelf ramp in the beginning of primary drying and that insufficient removal of water from the dried matrix caused viscous flow (product collapse). Regarding storage stability, moisture-induced degradation was confirmed in some of the formulations prepared by the slow ramp cycle, whereas all lyophilized BSA formulations prepared by the fast ramp cycle were stable. Thus, the results indicate that the ramp rate appears to be one of the critical operational parameters required to establish a successful lyophilization cycle. Copyright © 2018. Published by Elsevier B.V.

  16. Structure-function analysis of amino acid 74 of human RAMP1 and RAMP3 and its role in peptide interactions with adrenomedullin and calcitonin gene-related peptide receptors.

    PubMed

    Qi, Tao; Ly, Kien; Poyner, David R; Christopoulos, George; Sexton, Patrick M; Hay, Debbie L

    2011-05-01

    The receptors for calcitonin gene-related peptide (CGRP) and adrenomedullin (AM) are complexes of the calcitonin receptor-like receptor (CLR) and receptor activity-modifying proteins (RAMP). The CGRP receptor is a CLR/RAMP1 pairing whereas CLR/RAMP2 and CLR/RAMP3 constitute two subtypes of AM receptor: AM(1) and AM(2), respectively. Previous studies identified Glu74 in RAMP3 to be important for AM binding and potency. To further understand the importance of this residue and its equivalent in RAMP1 (Trp74) we substituted the native amino acids with several others. In RAMP3, these were Trp, Phe, Tyr, Ala, Ser, Thr, Arg and Asn; in RAMP1, Glu, Phe, Tyr, Ala and Asn substitutions were made. The mutant RAMPs were co-expressed with CLR in Cos7 cells; receptor function in response to AM, AM(2)/intermedin and CGRP was measured in a cAMP assay and cell surface expression was determined by ELISA. Phe reduced AM potency in RAMP3 but had no effect in RAMP1. In contrast, Tyr had no effect in RAMP3 but enhanced AM potency in RAMP1. Most other substitutions had a small effect on AM potency in both receptors whereas there was little impact on CGRP or AM(2) potency. Overall, these data suggest that the geometry and charge of the residue at position 74 contribute to how AM interacts with the AM(2) and CGRP receptors and confirms the role of this position in dictating differential AM pharmacology at the AM(2) and CGRP receptors. Copyright © 2011. Published by Elsevier Inc.

  17. Roles of CLR/RAMP Receptor Signaling in Reproduction and Development

    PubMed Central

    Chang, Chia Lin; Hsu, Sheau Yu Teddy

    2016-01-01

    Adrenomedullin (ADM), calcitonin gene-related peptides (α- and β-CGRPs), and intermedin/adrenomedullin 2 (IMD/ADM2) are major regulators of vascular tone and cardiovascular development in vertebrates. Recent research into their functions in reproduction has illuminated the role of these peptides and their cognate receptors (calcitonin receptor-like receptor/receptor activity-modifying protein (CLR/RAMP) receptors) in fetal–maternal blood circulation, feto-placental development, female gamete development, and gamete movement in the oviduct. Although ADM family peptides function in a temporally and spatially specific manner in various reproductive processes, they appear to act via a similar set of second messengers, including nitric oxide, cyclic GMP, cyclic AMP, and calcium-activated potassium channels in different tissues. These discoveries supported the view that CLR/RAMP receptors were recruited to perform a variety of newly evolved reproductive functions during the evolution of internal reproduction in mammals. These advances also provided insight into how CLR/RAMP receptor signaling pathways coordinate with other physiological adaptions to accommodate the extra metabolic needs during pregnancy, and captured some important details as to how fetal–maternal vascular communications are generated in the first place. Furthermore, these findings have revealed novel, promising opportunities for the prevention and treatment of aberrant pregnancies such as pregnancy-induced hypertension, preeclampsia, and tubal ectopic pregnancy. However, significant efforts are still needed to clarify the relationships between certain components of the CLR/RAMP signaling pathway and aberrant pregnancies before CLR/RAMP receptors can become targets for clinical management. With this understanding, this review summarizes recent progresses with particular focus on clinical implications. PMID:23745703

  18. Folding of a detachment and fault - Modified detachment folding along a lateral ramp, southwestern Montana, USA

    NASA Astrophysics Data System (ADS)

    Schmidt, Christopher; Whisner, S. Christopher; Whisner, Jennifer B.

    2014-12-01

    The inversion of the Middle Proterozoic Belt sedimentary basin during Late Cretaceous thrusting in Montana produced a large eastwardly-convex salient, the southern boundary of which is a 200 km-long oblique to lateral ramp subtended by a detachment between the Belt rocks and Archean basement. A 10 km-long lateral ramp segment exposes the upper levels of the detachment where hanging wall Belt rocks have moved out over the Paleozoic and Mesozoic section. The hanging wall structure consists of a train of high amplitude, faulted, asymmetrical detachment folds. Initial west-east shortening produced layer parallel shortening fabrics and dominantly strike slip faulting followed by symmetrical detachment folding. 'Lock-up' of movement on the detachment surface produced regional simple shear and caused the detachment folds to become asymmetrical and faulted. Folding of the detachment surface after lock-up modified the easternmost detachment folds further into a southeast-verging, overturned fold pair with a ramp-related fault along the base of the stretched mutual limb.

  19. Wind-Friendly Flexible Ramping Product Design in Multi-Timescale Power System Operations

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

    Cui, Mingjian; Zhang, Jie; Wu, Hongyu

    With increasing wind power penetration in the electricity grid, system operators are recognizing the need for additional flexibility, and some are implementing new ramping products as a type of ancillary service. However, wind is generally thought of as causing the need for ramping services, not as being a potential source for the service. In this paper, a multi-timescale unit commitment and economic dispatch model is developed to consider the wind power ramping product (WPRP). An optimized swinging door algorithm with dynamic programming is applied to identify and forecast wind power ramps (WPRs). Designed as positive characteristics of WPRs, the WPRPmore » is then integrated into the multi-timescale dispatch model that considers new objective functions, ramping capacity limits, active power limits, and flexible ramping requirements. Numerical simulations on the modified IEEE 118-bus system show the potential effectiveness of WPRP in increasing the economic efficiency of power system operations with high levels of wind power penetration. It is found that WPRP not only reduces the production cost by using less ramping reserves scheduled by conventional generators, but also possibly enhances the reliability of power system operations. Moreover, wind power forecasts play an important role in providing high-quality WPRP service.« less

  20. Terasaki Spiral Ramps in the Rough Endoplasmic Reticulum

    NASA Astrophysics Data System (ADS)

    Guven, Jemal; Huber, Greg; Valencia, Dulce María

    2014-10-01

    We present a model describing the morphology as well as the assembly of "Terasaki ramps," the recently discovered helicoidal connections linking adjacent sheets of the rough endoplasmic reticulum (ER). The fundamental unit is a localized symmetric double-ramped "parking garage" formed by two separated gently pitched, approximately helicoidal, ramps of opposite chiralities. This geometry is stabilized by a short-range repulsive interaction between ramps associated with bending energy which opposes the long-range attraction associated with tension. The ramp inner boundaries are themselves stabilized by the condensation of membrane-shaping proteins along their length. A mechanism for parking garage self-assembly is proposed involving the nucleation of dipoles at the center of tubular three-way junctions within the smooth ER. Our predictions are compared with the experimental data.

  1. Resident-Assisted Montessori Programming (RAMP): training persons with dementia to serve as group activity leaders.

    PubMed

    Camp, Cameron J; Skrajner, Michael J

    2004-06-01

    The purpose of this study was to determine the effects of an activity implemented by means of Resident-Assisted Montessori Programming (RAMP). Four persons with early-stage dementia were trained to serve as leaders for a small-group activity played by nine persons with more advanced dementia. Assessments of leaders' ability to learn the procedures of leading a group, as well as their satisfaction with this role, were taken, as were measures of players' engagement and affect during standard activities programming and RAMP activities. Leaders demonstrated the potential to fill the role of group activity leader effectively, and they expressed a high level of satisfaction with this role. Players' levels of positive engagement and pleasure during the RAMP activity were higher than during standard group activities. This study suggests that to the extent that procedural learning is available to persons with early-stage dementia, especially when they are assisted with external cueing, these individuals can successfully fill the role of volunteers when working with persons with more advanced dementia. This can provide a meaningful social role for leaders and increase access to high quality activities programming for large numbers of persons with dementia. Copyright 2004 The Gerontological Society of America

  2. A modified Lowry protein test for dilute protein solutions

    Treesearch

    Garold F. Gregory; Keith F. Jensen

    1971-01-01

    A modified Lowry protein test for dilute protein solutions modified Lowry protein test was compared with the standard Lowry protein test. The modified test was found to give estimates of protein concentration that were as good as the standard test and has the advange that proteins can be measured in very dilute solutions.

  3. Purification and complete amino acid sequence of a new type of sweet protein taste-modifying activity, curculin.

    PubMed

    Yamashita, H; Theerasilp, S; Aiuchi, T; Nakaya, K; Nakamura, Y; Kurihara, Y

    1990-09-15

    A new taste-modifying protein named curculin was extracted with 0.5 M NaCl from the fruits of Curculigo latifolia and purified by ammonium sulfate fractionation, CM-Sepharose ion-exchange chromatography, and gel filtration. Purified curculin thus obtained gave a single band having a Mr of 12,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the presence of 8 M urea. The molecular weight determined by low-angle laser light scattering was 27,800. These results suggest that native curculin is a dimer of a 12,000-Da polypeptide. The complete amino acid sequence of curculin was determined by automatic Edman degradation. Curculin consists of 114 residues. Curculin itself elicits a sweet taste. After curculin, water elicits a sweet taste, and sour substances induce a stronger sense of sweetness. No protein with both sweet-tasting and taste-modifying activities has ever been found. There are five sets of tripeptides common to miraculin (a taste-modifying protein), six sets of tripeptides common to thaumatin (a sweet protein), and two sets of tripeptides common to monellin (a sweet protein). Anti-miraculin serum was not immunologically reactive with curculin. The mechanism of the taste-modifying action of curculin is discussed.

  4. A microfluidic separation platform using an array of slanted ramps

    NASA Astrophysics Data System (ADS)

    Risbud, Sumedh; Bernate, Jorge; Drazer, German

    2013-03-01

    The separation of the different components of a sample is a crucial step in many micro- and nano-fluidic applications, including the detection of infections, the capture of circulating tumor cells, the isolation of proteins, RNA and DNA, to mention but a few. Vector chromatography, in which different species migrate in different directions in a planar microfluidic device thus achieving spatial as well as temporal resolution, offers the promise of high selectivity along with high throughput. In this work, we present a microfluidic vector chromatography platform consisting of slanted ramps in a microfluidic channel for the separation of suspended particles. We construct these ramps using inclined UV lithography, such that the inclined portion of the ramps is upstream. We show that particles of different size displace laterally to a different extent when driven by a flow field over a slanted ramp. The flow close to the ramp reorients along the ramp, causing the size-dependent deflection of the particles. The cumulative effect of an array of these ramps would cause particles of different size to migrate in different directions, thus allowing their passive and continuous separation.

  5. Rock ramp design guidelines

    USGS Publications Warehouse

    Mooney, David M.; Holmquist-Johnson, Christopher L.; Broderick, Susan

    2007-01-01

    Rock ramps or roughened channels consist of steep reaches stabilized by large immobile material (riprap). Primary objectives for rock ramps include: Create adequate head for diversionMaintain fish passage during low-flow conditionsMaintain hydraulic conveyance during high-flow conditionsSecondary objectives for rock ramp design include:Emulate natural systemsMinimize costsThe rock ramp consists of a low-flow channel designed to maintain biologically adequate depth and velocity conditions during periods of small discharges. The remainder of the ramp is designed to withstand and pass large flows with minimal structural damage. The following chapters outline a process for designing rock ramps.

  6. Evidence for Conservation of the Calcitonin Superfamily and Activity-regulating Mechanisms in the Basal Chordate Branchiostoma floridae: INSIGHTS INTO THE MOLECULAR AND FUNCTIONAL EVOLUTION IN CHORDATES.

    PubMed

    Sekiguchi, Toshio; Kuwasako, Kenji; Ogasawara, Michio; Takahashi, Hiroki; Matsubara, Shin; Osugi, Tomohiro; Muramatsu, Ikunobu; Sasayama, Yuichi; Suzuki, Nobuo; Satake, Honoo

    2016-01-29

    The calcitonin (CT)/CT gene-related peptide (CGRP) family is conserved in vertebrates. The activities of this peptide family are regulated by a combination of two receptors, namely the calcitonin receptor (CTR) and the CTR-like receptor (CLR), and three receptor activity-modifying proteins (RAMPs). Furthermore, RAMPs act as escort proteins by translocating CLR to the cell membrane. Recently, CT/CGRP family peptides have been identified or inferred in several invertebrates. However, the molecular characteristics and relevant functions of the CTR/CLR and RAMPs in invertebrates remain unclear. In this study, we identified three CT/CGRP family peptides (Bf-CTFPs), one CTR/CLR-like receptor (Bf-CTFP-R), and three RAMP-like proteins (Bf-RAMP-LPs) in the basal chordate amphioxus (Branchiostoma floridae). The Bf-CTFPs were shown to possess an N-terminal circular region typical of the CT/CGRP family and a C-terminal Pro-NH2. The Bf-CTFP genes were expressed in the central nervous system and in endocrine cells of the midgut, indicating that Bf-CTFPs serve as brain and/or gut peptides. Cell surface expression of the Bf-CTFP-R was enhanced by co-expression with each Bf-RAMP-LP. Furthermore, Bf-CTFPs activated Bf-CTFP-R·Bf-RAMP-LP complexes, resulting in cAMP accumulation. These results confirmed that Bf-RAMP-LPs, like vertebrate RAMPs, are prerequisites for the function and translocation of the Bf-CTFP-R. The relative potencies of the three peptides at each receptor were similar. Bf-CTFP2 was a potent ligand at all receptors in cAMP assays. Bf-RAMP-LP effects on ligand potency order were distinct to vertebrate CGRP/adrenomedullin/amylin receptors. To the best of our knowledge, this is the first molecular and functional characterization of an authentic invertebrate CT/CGRP family receptor and RAMPs. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. N(epsilon)-carboxymethyllysine-modified proteins are unable to bind to RAGE and activate an inflammatory response.

    PubMed

    Buetler, Timo M; Leclerc, Estelle; Baumeyer, Alexandra; Latado, Helia; Newell, John; Adolfsson, Oskar; Parisod, Véronique; Richoz, Janique; Maurer, Sarah; Foata, Francis; Piguet, Dominique; Junod, Sylviane; Heizmann, Claus W; Delatour, Thierry

    2008-03-01

    Advanced glycation endproducts (AGEs) containing carboxymethyllysine (CML) modifications are generally thought to be ligands of the receptor for AGEs, RAGEs. It has been argued that this results in the activation of pro-inflammatory pathways and diseases. However, it has not been shown conclusively that a CML-modified protein can interact directly with RAGE. Here, we have analyzed whether beta-lactoglobulin (bLG) or human serum albumin (HSA) modified chemically to contain only CML (10-40% lysine modification) can (i) interact with RAGE in vitro and (ii) interact with and activate RAGE in lung epithelial cells. Our results show that CML-modified bLG or HSA are unable to bind to RAGE in a cell-free assay system (Biacore). Furthermore, they are unable to activate pro-inflammatory signaling in the cellular system. Thus, CML probably does not form the necessary structure(s) to interact with RAGE and activate an inflammatory signaling cascade in RAGE-expressing cells.

  8. Ramp sedimentation in the Dinantian limestones of the Shannon Trough, Co. Limerick, Ireland

    NASA Astrophysics Data System (ADS)

    Somerville, Ian D.; Strogen, Peter

    1992-08-01

    During the late Chadian and Arundian (Lower Carboniferous), an extensive carbonate ramp (Limerick Ramp) developed over County Limerick, southwest Ireland, dipping northwestwards. Three distinct facies can be recognised corresponding to position on this ramp: inner, mid- and outer ramp. The inner ramp facies of oolitic and crinoidal grainstones (Herbertstown Limestone Formation) in east Limerick formed a major shoal behind which peritidal limestones were deposited. The mid-ramp facies of muddy bioclastic limestones and shales (Cooperhill facies) in north Limerick formed between fairweather and storm wave bases. The outer ramp (basinal) facies of mudstones and thin graded resedimented limestones (Rathkeale Beds) in west Limerick developed below storm wave base when fine terrigenous input was high. Later in the Arundian there was progradation of the nearshore oolitic and crinoidal grainstones over the mid-ramp facies. By the Holkerian, the deep-water basinal facies in west Limerick was buried beneath mid-ramp facies (Durnish Limestone). The initiation of the Limerick Ramp is closely related to the formation of the Shannon Trough. In the late Courceyan, accelerated subsidence in the Shannon area during deposition of Waulsortian facies marked the onset of a sag phase. Following a quiescent period in early Chadian, subsidence was renewed in the late Chadian and Arundian, when major facies changes occurred on the ramp. Comparison of the Shannon Trough with the Dublin Basin shows that in the latter, tectonic events in the Chadian and Arundian, particularly syn-sedimentary faulting, created a sharp division between platform and basinal sedimentation. Such tectonic influence is not recognised in the Shannon Trough. Here differential subsidence and eustatic sea-level changes led to more permanent ramp existence, modified only by westwards progradation.

  9. A new atomic force microscope force ramp technique using digital force feedback control reveals mechanically weak protein unfolding events.

    PubMed

    Kawakami, M; Smith, D A

    2008-12-10

    We have developed a new force ramp modification of the atomic force microscope (AFM) which can control multiple unfolding events of a multi-modular protein using software-based digital force feedback control. With this feedback the force loading rate can be kept constant regardless the length of soft elastic linkage or number of unfolded polypeptide domains. An unfolding event is detected as a sudden drop in force, immediately after which the feedback control reduces the applied force to a low value of a few pN by lowering the force set point. Hence the remaining folded domains can relax and the subsequent force ramp is applied to relaxed protein domains identically in each case. We have applied this technique to determine the kinetic parameters x(u), which is the distance between the native state and transition state, and α(0), which is the unfolding rate constant at zero force, for the mechanical unfolding of a pentamer of I27 domains of titin. In each force ramp the unfolding probability depends on the number of folded domains remaining in the system and we had to take account of this effect in the analysis of unfolding force data. We obtained values of x(u) and α(0) to be 0.28 nm and 1.02 × 10(-3) s(-1), which are in good agreement with those obtained from conventional constant velocity experiments. This method reveals unfolding data at low forces that are not seen in constant velocity experiments and corrects for the change in stiffness that occurs with most mechanical systems throughout the unfolding process to allow constant force ramp experiments to be carried out. In addition, a mechanically weak structure was detected, which formed from the fully extended polypeptide chain during a force quench. This indicates that the new technique will allow studies of the folding kinetics of previously hidden, mechanically weak species.

  10. Supersonic Elliptical Ramp Inlet

    NASA Technical Reports Server (NTRS)

    Adamson, Eric E. (Inventor); Fink, Lawrence E. (Inventor); Fugal, Spencer R. (Inventor)

    2016-01-01

    A supersonic inlet includes a supersonic section including a cowl which is at least partially elliptical, a ramp disposed within the cowl, and a flow inlet disposed between the cowl and the ramp. The ramp may also be at least partially elliptical.

  11. Precision linear ramp function generator

    DOEpatents

    Jatko, W.B.; McNeilly, D.R.; Thacker, L.H.

    1984-08-01

    A ramp function generator is provided which produces a precise linear ramp function which is repeatable and highly stable. A derivative feedback loop is used to stabilize the output of an integrator in the forward loop and control the ramp rate. The ramp may be started from a selected baseline voltage level and the desired ramp rate is selected by applying an appropriate constant voltage to the input of the integrator.

  12. Precision linear ramp function generator

    DOEpatents

    Jatko, W. Bruce; McNeilly, David R.; Thacker, Louis H.

    1986-01-01

    A ramp function generator is provided which produces a precise linear ramp unction which is repeatable and highly stable. A derivative feedback loop is used to stabilize the output of an integrator in the forward loop and control the ramp rate. The ramp may be started from a selected baseline voltage level and the desired ramp rate is selected by applying an appropriate constant voltage to the input of the integrator.

  13. Phosphate-Modified Nucleotides for Monitoring Enzyme Activity.

    PubMed

    Ermert, Susanne; Marx, Andreas; Hacker, Stephan M

    2017-04-01

    Nucleotides modified at the terminal phosphate position have been proven to be interesting entities to study the activity of a variety of different protein classes. In this chapter, we present various types of modifications that were attached as reporter molecules to the phosphate chain of nucleotides and briefly describe the chemical reactions that are frequently used to synthesize them. Furthermore, we discuss a variety of applications of these molecules. Kinase activity, for instance, was studied by transfer of a phosphate modified with a reporter group to the target proteins. This allows not only studying the activity of kinases, but also identifying their target proteins. Moreover, kinases can also be directly labeled with a reporter at a conserved lysine using acyl-phosphate probes. Another important application for phosphate-modified nucleotides is the study of RNA and DNA polymerases. In this context, single-molecule sequencing is made possible using detection in zero-mode waveguides, nanopores or by a Förster resonance energy transfer (FRET)-based mechanism between the polymerase and a fluorophore-labeled nucleotide. Additionally, fluorogenic nucleotides that utilize an intramolecular interaction between a fluorophore and the nucleobase or an intramolecular FRET effect have been successfully developed to study a variety of different enzymes. Finally, also some novel techniques applying electron paramagnetic resonance (EPR)-based detection of nucleotide cleavage or the detection of the cleavage of fluorophosphates are discussed. Taken together, nucleotides modified at the terminal phosphate position have been applied to study the activity of a large diversity of proteins and are valuable tools to enhance the knowledge of biological systems.

  14. Physical activity modifies the association between dietary protein and lean mass of postmenopausal women

    PubMed Central

    Martinez, Jessica A.; Wertheim, Betsy C.; Thomson, Cynthia A.; Bea, Jennifer W.; Wallace, Robert; Allison, Matthew; Snetselaa, Linda; Chen, Zhao; Nassir, Rami; Thompson, Patricia A.

    2016-01-01

    Background Maintenance of lean muscle mass and related strength is associated with lower risk for numerous chronic diseases of aging in women. Objective To evaluate whether the association between dietary protein and lean mass differs by physical activity level, amino acid composition, and body mass index categories. Design Cross-sectional analysis of a prospective cohort. Participants/setting Postmenopausal women from the Women’s Health Initiative with body composition measurements by dual-energy X-ray absorptiometry (n=8,298). Main outcome measures Percent lean mass, percent fat mass and lean body mass index. Statistical analyses performed Linear regression models adjusted for scanner serial number, age, calibrated energy intake, race/ethnicity, neighborhood socioeconomic status, and recreational physical activity were used to determine the relationship between protein intake and body composition measures. Likelihood ratio tests and stratified analysis were used to investigate physical activity and body mass index as potential effect modifiers. Results Biomarker-calibrated protein intake was positively associated with percent lean mass; women in the highest protein quintile had 6.3 percentage points higher lean mass than the lowest quintile (P < 0.001). This difference rose to 8.5 percentage points for physically active women in the highest protein quintile (Pinteraction = 0.023). Percent fat mass and lean body mass index were both inversely related to protein intake (both P < 0.001). Physical activity further reduced percent fat mass (Pinteraction = 0.022) and lean body mass index (Pinteraction = 0.011). Leucine intake was associated with lean mass, as were branched chain amino acids combined (both P < 0.001), but not independent of total protein. All associations were observed for normal-weight, overweight, and obese women. Conclusions Protein consumption up to 2.02 g/kg body weight daily is positively associated with lean mass in postmenopausal women

  15. Physical Activity Modifies the Association between Dietary Protein and Lean Mass of Postmenopausal Women.

    PubMed

    Martinez, Jessica A; Wertheim, Betsy C; Thomson, Cynthia A; Bea, Jennifer W; Wallace, Robert; Allison, Matthew; Snetselaar, Linda; Chen, Zhao; Nassir, Rami; Thompson, Patricia A

    2017-02-01

    Maintenance of lean muscle mass and related strength is associated with lower risk for numerous chronic diseases of aging in women. Our aim was to evaluate whether the association between dietary protein and lean mass differs by physical activity level, amino acid composition, and body mass index categories. We performed a cross-sectional analysis of a prospective cohort. Participants were postmenopausal women from the Women's Health Initiative with body composition measurements by dual-energy x-ray absorptiometry (n=8,298). Our study measured percent lean mass, percent fat mass, and lean body mass index. Linear regression models adjusted for scanner serial number, age, calibrated energy intake, race/ethnicity, neighborhood socioeconomic status, and recreational physical activity were used to determine the relationship between protein intake and body composition measures. Likelihood ratio tests and stratified analysis were used to investigate physical activity and body mass index as potential effect modifiers. Biomarker-calibrated protein intake was positively associated with percent lean mass; women in the highest protein quintile had 6.3 percentage points higher lean mass than the lowest quintile (P<0.001). This difference rose to 8.5 percentage points for physically active women in the highest protein quintile (P interaction =0.023). Percent fat mass and lean body mass index were both inversely related to protein intake (both P<0.001). Physical activity further reduced percent fat mass (P interaction =0.022) and lean body mass index (P interaction =0.011). Leucine intake was associated with lean mass, as were branched chain amino acids combined (both P<0.001), but not independent of total protein. All associations were observed for normal-weight, overweight, and obese women. Protein consumption up to 2.02 g/kg body weight daily is positively associated with lean mass in postmenopausal women. Importantly, those that also engage in physical activity have the

  16. Turning behaviors of T cells climbing up ramp-like structures are regulated by myosin light chain kinase activity and lamellipodia formation.

    PubMed

    Song, Kwang Hoon; Lee, Jaehyun; Jung, Hong-Ryul; Park, HyoungJun; Doh, Junsang

    2017-09-14

    T cells navigate diverse microenvironments to perform immune responses. Micro-scale topographical structures within the tissues, which may inherently exist in normal tissues or may be formed by inflammation or injury, can influence T cell migration, but how T cell migration is affected by such topographical structures have not been investigated. In this study, we fabricated ramp-like structures with a 5 μm height and various slopes, and observed T cells climbing up the ramp-like structures. T cells encountering the ramp-like structures exhibited MLC accumulation near head-tail junctions contacting the ramp-like structures, and made turns to the direction perpendicular to the ramp-like structures. Pharmacological study revealed that lamellipodia formation mediated by arp2/3 and contractility regulated by myosin light chain kinase (MLCK) were responsible for the intriguing turning behavior of T cells climbing the ramp-like structures. Arp2/3 or MLCK inhibition substantially reduced probability of T cells climbing sharp-edged ramp-like structures, indicating intriguing turning behavior of T cells mediated by lamellipodia formation and MLCK activity may be important for T cells to access inflamed or injured tissues with abrupt topographical changes.

  17. Examining Relay Ramp Evolution Through Paleo-shoreline Deformation Analysis, Warner Valley Fault, Oregon

    NASA Astrophysics Data System (ADS)

    Young, C. S.; Dawers, N. H.

    2017-12-01

    Fault growth is often accomplished by linking a series of en echelon faults through relay ramps. A relay ramp is the area between two overlapping fault segments that tilts and deforms as the faults accrue displacement. The structural evolution of breached normal fault relay ramps remains poorly understood because of the difficulty in defining how slip is partitioned between the most basinward fault (known as the outboard fault), the overlapping fault (inboard fault), and any ramp-breaching linking faults. Along the Warner Valley fault in south-central Oregon, two relay ramps displaying different fault linkage geometries are lined with a series of paleo-lacustrine shorelines that record a Pleistocene paleolake regression. The inner edges of these shorelines act as paleo-horizontal datums that have been deformed by fault activity, and are used to measure relative slip variations across the relay ramp bounding faults. By measuring the elevation changes using a 10m digital elevation model (DEM) of shoreline inner edges, we estimate the amount of slip partitioned between the inboard, outboard and ramp-breaching linking faults. In order to attribute shoreline deformation to fault activity we identify shoreline elevation anomalies, where deformation exceeds a ± 3.34 m window, which encompass our conservative estimates of natural variability in the shoreline geomorphology and the error associated with the data collection. Fault activity along the main length of the fault for each ramp-breaching style is concentrated near the intersection of the linking fault and the outboard portion of the main fault segment. However, fault activity along the outboard fault tip varies according to breaching style. At a footwall breach the entire outboard fault tip appears relatively inactive. At a mid-ramp breach the outboard fault tip remains relatively active because of the proximity of the linking fault to this fault tip.

  18. Measuring the effectiveness of ramp metering strategies on I-12 : [tech summary].

    DOT National Transportation Integrated Search

    2013-10-01

    In recent years, more emphasis has been placed on Active Traffi c Management (ATM) strategies such as speed harmonization, managed lanes, and : ramp metering. Ramp metering is one of the successful active traffi c control strategies, controlling the ...

  19. Phase transition of a new lattice hydrodynamic model with consideration of on-ramp and off-ramp

    NASA Astrophysics Data System (ADS)

    Zhang, Geng; Sun, Di-hua; Zhao, Min

    2018-01-01

    A new traffic lattice hydrodynamic model with consideration of on-ramp and off-ramp is proposed in this paper. The influence of on-ramp and off-ramp on the stability of the main road is uncovered by theoretical analysis and computer simulation. Through linear stability theory, the neutral stability condition of the new model is obtained and the results show that the unstable region in the phase diagram is enlarged by considering the on-ramp effect but shrunk with consideration of the off-ramp effect. The mKdV equation near the critical point is derived via nonlinear reductive perturbation method and the occurrence of traffic jamming transition can be described by the kink-antikink soliton solution of the mKdV equation. From the simulation results of space-time evolution of traffic density waves, it is shown that the on-ramp can worsen the traffic stability of the main road but off-ramp is positive in stabilizing the traffic flow of the main road.

  20. Pathfinder Rear Ramp

    NASA Image and Video Library

    1997-07-06

    NASA's Mars Pathfinder's rear rover ramp can be seen successfully unfurled in this image, taken at the end of Sol 2 by the Imager for Mars Pathfinder (IMP). This ramp was later used for the deployment of the microrover Sojourner, which occurred at the end of Sol 2. Areas of a lander petal and deflated airbag are visible at left. The image helped Pathfinder scientists determine that the rear ramp was the one to use for rover deployment. At upper right is the rock dubbed "Barnacle Bill," which Sojourner will later study. http://photojournal.jpl.nasa.gov/catalog/PIA00627

  1. Measuring the effectiveness of ramp metering strategies on I-12.

    DOT National Transportation Integrated Search

    2013-10-01

    Ramp metering is one of the successful traffic control strategies in the area of active traffic and demand management. This study evaluates the : effectiveness of a fixed time ramp metering control on the day to day operation of traffic over two segm...

  2. Optical monitoring of neuronal activity at high frame rate with a digital random-access multiphoton (RAMP) microscope.

    PubMed

    Otsu, Yo; Bormuth, Volker; Wong, Jerome; Mathieu, Benjamin; Dugué, Guillaume P; Feltz, Anne; Dieudonné, Stéphane

    2008-08-30

    Two-photon microscopy offers the promise of monitoring brain activity at multiple locations within intact tissue. However, serial sampling of voxels has been difficult to reconcile with millisecond timescales characteristic of neuronal activity. This is due to the conflicting constraints of scanning speed and signal amplitude. The recent use of acousto-optic deflector scanning to implement random-access multiphoton microscopy (RAMP) potentially allows to preserve long illumination dwell times while sampling multiple points-of-interest at high rates. However, the real-life abilities of RAMP microscopy regarding sensitivity and phototoxicity issues, which have so far impeded prolonged optical recordings at high frame rates, have not been assessed. Here, we describe the design, implementation and characterisation of an optimised RAMP microscope. We demonstrate the application of the microscope by monitoring calcium transients in Purkinje cells and cortical pyramidal cell dendrites and spines. We quantify the illumination constraints imposed by phototoxicity and show that stable continuous high-rate recordings can be obtained. During these recordings the fluorescence signal is large enough to detect spikes with a temporal resolution limited only by the calcium dye dynamics, improving upon previous techniques by at least an order of magnitude.

  3. Using modified soy protein to enhance foaming of egg white protein.

    PubMed

    Wang, Guang; Troendle, Molly; Reitmeier, Cheryll A; Wang, Tong

    2012-08-15

    It is well known that the foaming properties of egg white protein are significantly reduced when a small amount of yolk is mixed in the white. To improve foaming properties of yolk-contaminated egg white protein, soy protein isolate (SPI) and egg proteins were modified to make basic proteins, and effects of these modified proteins on egg white foaming were evaluated in a model and an angel cake system. SPI and egg yolk proteins were modified to have an isoelectric point of 10, and sonication was used to increase protein dispersibility after the ethyl esterification reaction. However, only the addition of sonicated and modified SPI (SMSPI) showed improvement of foaming in the 5% egg protein model system with 0.4% yolk addition. SMSPI was then used in making angel food cake to examine whether the cake performance reduction due to yolk contamination of the white would be restored by such alkaline protein. Cake performance was improved when cream of tartar was used together with SMSPI. Basic soy protein can be made and used to improve egg white foaming properties and cake performance. Copyright © 2012 Society of Chemical Industry.

  4. Predicting Cell Association of Surface-Modified Nanoparticles Using Protein Corona Structure - Activity Relationships (PCSAR).

    PubMed

    Kamath, Padmaja; Fernandez, Alberto; Giralt, Francesc; Rallo, Robert

    2015-01-01

    Nanoparticles are likely to interact in real-case application scenarios with mixtures of proteins and biomolecules that will absorb onto their surface forming the so-called protein corona. Information related to the composition of the protein corona and net cell association was collected from literature for a library of surface-modified gold and silver nanoparticles. For each protein in the corona, sequence information was extracted and used to calculate physicochemical properties and statistical descriptors. Data cleaning and preprocessing techniques including statistical analysis and feature selection methods were applied to remove highly correlated, redundant and non-significant features. A weighting technique was applied to construct specific signatures that represent the corona composition for each nanoparticle. Using this basic set of protein descriptors, a new Protein Corona Structure-Activity Relationship (PCSAR) that relates net cell association with the physicochemical descriptors of the proteins that form the corona was developed and validated. The features that resulted from the feature selection were in line with already published literature, and the computational model constructed on these features had a good accuracy (R(2)LOO=0.76 and R(2)LMO(25%)=0.72) and stability, with the advantage that the fingerprints based on physicochemical descriptors were independent of the specific proteins that form the corona.

  5. Congestion-Responsive On-Ramp Metering : Before and After Studies - Phase 1

    DOT National Transportation Integrated Search

    2016-07-06

    The objective of this project was to develop recommendations toward a statewide policy of congestion responsive freeway ramp metering operation. The research is performed in two phases. In phase 1, alternative ramp metering activation strategies were...

  6. Functional expression of the taste-modifying protein, miraculin, in transgenic lettuce.

    PubMed

    Sun, Hyeon-Jin; Cui, Min-Long; Ma, Biao; Ezura, Hiroshi

    2006-01-23

    Taste-modifying proteins are a natural alternative to artificial sweeteners and flavor enhancers and have been used in some cultures for centuries. The taste-modifying protein, miraculin, has the unusual property of being able to modify a sour taste into a sweet taste. Here, we report the use of a plant expression system for the production of miraculin. A synthetic gene encoding miraculin was placed under the control of constitutive promoters and transferred to lettuce. Expression of this gene in transgenic lettuce resulted in the accumulation of significant amounts of miraculin protein in the leaves. The miraculin expressed in transgenic lettuce possessed sweetness-inducing activity. These results demonstrate that the production of miraculin in edible plants can be a good alternative strategy to enhance the availability of this protein.

  7. 78 FR 69397 - Agency Information Collection Activities; Comment Request; Implementation Study of the Ramp Up to...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-19

    ... DEPARTMENT OF EDUCATION [Docket No. ED-2013-ICCD-0142] Agency Information Collection Activities; Comment Request; Implementation Study of the Ramp Up to Readiness Program AGENCY: Institute of Education Sciences/National Center for Education Statistics (IES), Department of Education (ED). ACTION: Notice...

  8. Generation and purification of highly-specific antibodies for detecting post-translationally modified proteins in vivo

    PubMed Central

    Arur, Swathi; Schedl, Tim

    2014-01-01

    Post-translational modifications alter protein structure, affecting activity, stability, localization and/or binding partners. Antibodies that specifically recognize post-translationally modified proteins have a number of uses including immuno-cytochemistry and immuno-precipitation of the modified protein to purify protein-protein and protein-nucleic acid complexes. However, antibodies directed at modified sites on individual proteins are often non-specific. Here we describe a protocol to purify polyclonal antibodies that specifically detect the modified protein of interest. The approach uses iterative rounds of subtraction and affinity purification, using stringent washes to remove antibodies that recognize the unmodified protein and low sequence complexity epitopes containing the modified amino acid. Dot and western blots assays are employed to assess antibody preparation specificity. The approach is designed to overcome the common occurrence that a single round of subtraction and affinity purification is not sufficient to obtain a modified protein specific antibody preparation. One full round of antibody purification and specificity testing takes 6 days of discontinuous time. PMID:24457330

  9. Mars pathfinder Rover egress deployable ramp assembly

    NASA Technical Reports Server (NTRS)

    Spence, Brian R.; Sword, Lee F.

    1996-01-01

    The Mars Pathfinder Program is a NASA Discovery Mission, led by the Jet Propulsion Laboratory, to launch and place a small planetary Rover for exploration on the Martian surface. To enable safe and successful egress of the Rover vehicle from the spacecraft, a pair of flight-qualified, deployable ramp assemblies have been developed. This paper focuses on the unique, lightweight deployable ramp assemblies. A brief mission overview and key design requirements are discussed. Design and development activities leading to qualification and flight systems are presented.

  10. Ramp meter design manual

    DOT National Transportation Integrated Search

    2000-01-01

    Caltrans is committed to using ramp metering as an effective traffic management strategy to maintain an efficient freeway system and protect the investment made in constructing freeways by keeping them operating at or near capacity. Ramp Metering is ...

  11. Reevaluation of Ramp Design Speed Criteria

    DOT National Transportation Integrated Search

    1999-12-01

    Current freeway entry ramp design speed criteria were evaluated through observations of twenty ramps in four Texas cities. Field observations of ramp and freeway traffic speed-distance relationships were made using videotaping methods. Traffic operat...

  12. Characteristics and safety assessment of intractable proteins in genetically modified crops.

    PubMed

    Bushey, Dean F; Bannon, Gary A; Delaney, Bryan F; Graser, Gerson; Hefford, Mary; Jiang, Xiaoxu; Lee, Thomas C; Madduri, Krishna M; Pariza, Michael; Privalle, Laura S; Ranjan, Rakesh; Saab-Rincon, Gloria; Schafer, Barry W; Thelen, Jay J; Zhang, John X Q; Harper, Marc S

    2014-07-01

    Genetically modified (GM) crops may contain newly expressed proteins that are described as "intractable". Safety assessment of these proteins may require some adaptations to the current assessment procedures. Intractable proteins are defined here as those proteins with properties that make it extremely difficult or impossible with current methods to express in heterologous systems; isolate, purify, or concentrate; quantify (due to low levels); demonstrate biological activity; or prove equivalency with plant proteins. Five classes of intractable proteins are discussed here: (1) membrane proteins, (2) signaling proteins, (3) transcription factors, (4) N-glycosylated proteins, and (5) resistance proteins (R-proteins, plant pathogen recognition proteins that activate innate immune responses). While the basic tiered weight-of-evidence approach for assessing the safety of GM crops proposed by the International Life Sciences Institute (ILSI) in 2008 is applicable to intractable proteins, new or modified methods may be required. For example, the first two steps in Tier I (hazard identification) analysis, gathering of applicable history of safe use (HOSU) information and bioinformatics analysis, do not require protein isolation. The extremely low level of expression of most intractable proteins should be taken into account while assessing safety of the intractable protein in GM crops. If Tier II (hazard characterization) analyses requiring animal feeding are judged to be necessary, alternatives to feeding high doses of pure protein may be needed. These alternatives are discussed here. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Generation of thromboxane A2 and aorta-contracting activity from platelets stimulated with modified C-reactive protein.

    PubMed Central

    Simpson, R M; Prancan, A; Izzi, J M; Fiedel, B A

    1982-01-01

    The classical acute phase reactant, C-reactive protein (CRP), appears in markedly elevated concentration in the sera of individuals undergoing reactions of acute inflammation and tissue degradation. We previously demonstrated that like IgG, appropriately purified CRP could be thermally modified (H-CRP) such that it enhanced platelet activation in plasma and initiated platelet responses in isolated systems. We now report that this direct platelet activation by modified CRP results in the secretion of both platelet dense body and alpha-granule constituents, and is sensitive to non-steroidal anti-inflammatory drugs as well as the adenosine diphosphate (ADP)-removing enzyme system creatine phosphate/creatine phosphokinase. Thin-layer chromatographic (TLC) analysis of prostanoate endproducts following platelet activation with H-CRP revealed the formation of thromboxane B2 (the hydrated endproduct of thromboxane A2), an important endogenous platelet activator and contractor of vascular tissue; bioassay on rabbit aorta strips of supernatants obtained from platelets undergoing challenge with H-CRP supported the TLC analysis. Complexes formed between CRP and one major ligand, the polycation, were found to share certain platelet activating properties with H-CRP, as does latex-aggregated CRP. These data imply a potential agonist role for this acute phase reactant in platelet physiology and suggest that the interaction of modified forms of CRP with the platelet at sites of vascular damage could have pathological significance. PMID:7118160

  14. Protein kinase C negatively regulates Akt activity and modifies UVC-induced apoptosis in mouse keratinocytes.

    PubMed

    Li, Luowei; Sampat, Keeran; Hu, Nancy; Zakari, Julia; Yuspa, Stuart H

    2006-02-10

    Skin keratinocytes are subject to frequent chemical and physical injury and have developed elaborate cell survival mechanisms to compensate. Among these, the Akt/protein kinase B (PKB) pathway protects keratinocytes from the toxic effects of ultraviolet light (UV). In contrast, the protein kinase C (PKC) family is involved in several keratinocyte death pathways. During an examination of potential interactions among these two pathways, we found that the insulin-like growth factor (IGF-1) activates both the PKC and the Akt signaling pathways in cultured primary mouse keratinocytes as indicated by increased phospho-PKC and phospho-Ser-473-Akt. IGF-1 also selectively induced translocation of PKCdelta and PKCepsilon from soluble to particulate fractions in mouse keratinocytes. Furthermore, the PKC-specific inhibitor, GF109203X, increased IGF-1-induced phospho-Ser-473-Akt and Akt kinase activity and enhanced IGF-1 protection from UVC-induced apoptosis. Selective activation of PKC by 12-O-tetradecanoylphorbol-13-acetate (TPA) reduced phospho-Ser-473-Akt, suggesting that activation of PKC inhibits Akt activity. TPA also attenuated IGF-1 and epidermal growth factor-induced phospho-Ser-473-Akt, reduced Akt kinase activity, and blocked IGF-1 protection from UVC-induced apoptosis. The inhibition of Akt activity by TPA was reduced by inhibitors of protein phosphatase 2A, and TPA stimulated the association of phosphatase 2A with Akt. Individual PKC isoforms were overexpressed in cultured keratinocytes by transduction with adenoviral vectors or inhibited with PKC-selective inhibitors. These studies indicated that PKCdelta and PKCepsilon were selectively potent at causing dephosphorylation of Akt and modifying cell survival, whereas PKCalpha enhanced phosphorylation of Akt on Ser-473. Our results suggested that activation of PKCdelta and PKCepsilon provide a negative regulation for Akt phosphorylation and kinase activity in mouse keratinocytes and serve as modulators of cell

  15. Freeway ramp management in Pennsylvania.

    DOT National Transportation Integrated Search

    2011-03-31

    This research identified the opportunities to implement ramp management strategies on freeways in Pennsylvania. The research : explored the need to integrate local arterial traffic signal systems with ramp management strategies to reduce the impacts ...

  16. Cardiac-Activity Measures for Assessing Airport Ramp-Tower Controller's Workload

    NASA Technical Reports Server (NTRS)

    Hayashi, Miwa; Dulchinos, Victoria

    2016-01-01

    Heart rate (HR) and heart rate variability (HRV) potentially offer objective, continuous, and non-intrusive measures of human-operators mental workload. Such measurement capability is attractive for workload assessment in complex laboratory simulations or safety-critical field testing. The present study compares mean HR and HRV data with self-reported subjective workload ratings collected during a high-fidelity human-in-the-loop simulation of airport ramp traffic control operations, which involve complex cognitive and coordination tasks. Mean HR was found to be weakly sensitive to the workload ratings, while HRV was not sensitive or even contradictory to the assumptions. Until more knowledge on stress response mechanisms of the autonomic nervous system is obtained, it is recommended that these cardiac-activity measures be used with other workload assessment tools, such as subjective measures.

  17. Cardiac-Activity Measures for Assessing Airport Ramp-Tower Controller's Workload

    NASA Technical Reports Server (NTRS)

    Hayashi, Miwa; Dulchinos, Victoria L.

    2016-01-01

    Heart rate (HR) and heart rate variability (HRV) potentially offer objective, continuous, and non-intrusive measures of human-operator's mental workload. Such measurement capability is attractive for workload assessment in complex laboratory simulations or safety-critical field testing. The present study compares mean HR and HRV data with self-reported subjective workload ratings collected during a high-fidelity human-in-the-loop simulation of airport ramp traffic control operations, which involve complex cognitive and coordination tasks. Mean HR was found to be weakly sensitive to the workload ratings, while HRV was not sensitive or even contradictory to the assumptions. Until more knowledge on stress response mechanisms of the autonomic nervous system is obtained, it is recommended that these cardiac-activity measures be used with other workload assessment tools, such as subjective measures.

  18. Evaluation of a fuzzy logic ramp metering algorithm : a comparative study among three ramp metering algorithms used in the greater Seattle area

    DOT National Transportation Integrated Search

    2000-02-01

    A Fuzzy Logic Ramp Metering Algorithm was implemented on 126 ramps in the greater Seattle area. Two multiple-ramp study sites were evaluted by comparing the fuzzy logic controller (FLC) to the other two ramp metering algorithms in operation at those ...

  19. Understanding Micro-Ramp Control for Shock Boundary Layer Interactions

    DTIC Science & Technology

    2008-02-07

    micro-ramps on a supersonic boundary layer at M=3.0 was investigated using monotone integrated Large Eddy Simulations (MILES) and Reynolds Averaged Navier... Supersonic boundary layer flow with micro-ramp and no shock wave 3.2 SBLI with no micro-ramp 3.3 SBLI with micro-ramp 3.4 Micro-ramp size and location IV . C...ramps on a supersonic boundary layer at M=3.0 was investigated using monotone integrated Large Eddy Simulations (MILES) and Reynolds Averaged Navier

  20. APPALACHIAN FOLDS, LATERAL RAMPS, AND BASEMENT FAULTS: A MODERN ENGINEERING PROBLEM?

    USGS Publications Warehouse

    Pohn, Howard A.

    1987-01-01

    Field studies and analysis of radar data have shown that cross-strike faulting in the central and southern Appalachians has affected geologic structures at the surface. These basement faults appear to have been active through much of geologic time. Indeed, more than 45 percent of modern earthquakes occur along these narrow zones here termed 'lateral ramps. ' Because of this seismic activity, these lateral ramps are likely to be zones that are prone to slope failure. The engineer should be aware of the presence of such zones and the higher landslide potential along them.

  1. Advanced glycation end product (AGE) modified proteins in tears of diabetic patients.

    PubMed

    Zhao, Zhenjun; Liu, Jingfang; Shi, Bingyin; He, Shuixiang; Yao, Xiaoli; Willcox, Mark D P

    2010-08-11

    High glucose level in diabetic patients may lead to advanced glycation end product (AGE) modified proteins. This study investigated AGE modified proteins in tears and compared their levels in diabetic patients (DM) with non-diabetic controls (CTL). Basal tears were collected from DM with (DR) or without (DNR) retinopathy and CTL. Total AGE modified proteins were detected quantitatively by a dot immunobinding assay. The AGE modified proteins were separated in 1D- and 2D-SDS gels and detected by western-blotting. The individual AGE modified proteins were also compared between groups using densitometry. Compared with the CTL group, tear concentrations of AGE modified proteins were significantly elevated in DR and DNR groups. The concentration of AGE modified proteins in diabetic tears were positively correlated with AGE modified hemoglobin (HbA1c) and postprandial blood glucose level (PBG). Western blotting of AGE modified proteins from 1D-SDS gels showed several bands, the major one at around 60 kDa. The intensities of AGE modified protein bands were higher in DM tears than in CTL tears. Western blotting from 2D-SDS gels showed a strongly stained horizontal strip, which corresponded to the major band in 1D-SDS gels. Most of the other AGE modified protein species were within molecular weight of 30-60 kDa, PI 5.2-7.0. Densitometry analysis demonstrated several AGE modified proteins were elevated in DR or DNR tears. Total and some individual AGE modified proteins were elevated in DM tears. AGE modified proteins in tears may be used as biomarkers to diagnose diabetes and/or diabetic retinopathy.

  2. Portable and Lightweight Ramp Structure

    DTIC Science & Technology

    2001-04-09

    long side of which is in abutting relationship with the 12 short side of the end of the ramp. Fastener receivers are equi- 13 spaced in duplicate...The modular sections are conveniently prefabricated 18 1 and provided in kit form to the number of sections corresponding 2 to the desired ramp

  3. Adhesives from modified soy protein

    DOEpatents

    Sun, Susan [Manhattan, KS; Wang, Donghai [Manhattan, KS; Zhong, Zhikai [Manhattan, KS; Yang, Guang [Shanghai, CN

    2008-08-26

    The present invention provides useful adhesive compositions having similar adhesive properties to conventional UF and PPF resins. The compositions generally include a protein portion and modifying ingredient portion selected from the group consisting of carboxyl-containing compounds, aldehyde-containing compounds, epoxy group-containing compounds, and mixtures thereof. The composition is preferably prepared at a pH level at or near the isoelectric point of the protein. In other preferred forms, the adhesive composition includes a protein portion and a carboxyl-containing group portion.

  4. True Triaxial Experimental Study of Rockbursts Induced By Ramp and Cyclic Dynamic Disturbances

    NASA Astrophysics Data System (ADS)

    Su, Guoshao; Hu, Lihua; Feng, Xiating; Yan, Liubin; Zhang, Gangliang; Yan, Sizhou; Zhao, Bin; Yan, Zhaofu

    2018-04-01

    A modified rockburst testing system was utilized to reproduce rockbursts induced by ramp and cyclic dynamic disturbances with a low-intermediate strain rate of 2 × 10-3-5 × 10-3 s-1 in the laboratory. The experimental results show that both the ramp and cyclic dynamic disturbances play a significant role in inducing rockbursts. In the tests of rockbursts induced by a ramp dynamic disturbance, as the static stress before the dynamic disturbance increases, both the strength of specimens and the kinetic energy of the ejected fragments first increase and then decrease. In the tests of rockbursts induced by a cyclic dynamic disturbance, there exists a rockburst threshold of the static stress and the dynamic disturbance amplitude, and the kinetic energy of the ejected fragments first increases and then decreases as the cyclic dynamic disturbance frequency increases. The main differences between rockbursts induced by ramp dynamic disturbances and those induced by cyclic dynamic disturbances are as follows: the rockburst development process of the former is characterized by an impact failure feature, while that of the latter is characterized by a fatigue failure feature; the damage evolution curve of the specimen of the former has a leap-developing form with a significant catastrophic feature, while that of the latter has an inverted S-shape with a remarkable fatigue damage characteristic; the energy mechanism of the former involves the ramp dynamic disturbance giving extra elastic strain energy to rocks, while that of the latter involves the cyclic dynamic disturbance decreasing the ultimate energy storage capacity of rocks.

  5. Analogue modelling of thrust systems: Passive vs. active hanging wall strain accommodation and sharp vs. smooth fault-ramp geometries

    NASA Astrophysics Data System (ADS)

    Rosas, F. M.; Duarte, J. C.; Almeida, P.; Schellart, W. P.; Riel, N.; Terrinha, P.

    2017-06-01

    We present new analogue modelling results of crustal thrust-systems in which a deformable (brittle) hanging wall is assumed to endure passive internal deformation during thrusting, i.e. exclusively as a consequence of having to adapt its shape to the variable geometry of a rigid footwall. Building on previous experimental contributions, we specifically investigate the role of two so far overlooked critical variables: a) concave-convex (CC) vs. flat-ramp-flat (FRF) thrust ramp geometry; and b) presence vs. absence of a basal velocity discontinuity (VD). Regarding the first variable, we compare new results for considered (CC) smoother ramp types against classical experiments in which (FRF) sharp ramp geometries are always prescribed. Our results show that the considered sharp vs. smooth variation in the thrust-ramp geometry produces important differences in the distribution of the local stress field in the deformable hanging wall above both (lower and upper) fault bends, with corresponding styles of strain accommodation being expressed by marked differences in measured morpho-structural parameters. Regarding the second variable, we for the first time report analogue modelling results of this type of experiments in which basal VDs are experimentally prescribed to be absent. Our results critically show that true passive hanging wall deformation is only possible to simulate in the absence of any basal VD, since active shortening accommodation always necessarily occurs in the hanging wall above such a discontinuity (i.e. above the lower fault bend). In addition, we show that the morpho-structural configuration of model thrust-wedges formed for prescribed VD absence conditions complies well with natural examples of major overthrusts, wherein conditions must occur that approximate a frictionless state along the main basal thrust-plane.

  6. A polyhedral study of production ramping

    DOE PAGES

    Damci-Kurt, Pelin; Kucukyavuz, Simge; Rajan, Deepak; ...

    2015-06-12

    Here, we give strong formulations of ramping constraints—used to model the maximum change in production level for a generator or machine from one time period to the next—and production limits. For the two-period case, we give a complete description of the convex hull of the feasible solutions. The two-period inequalities can be readily used to strengthen ramping formulations without the need for separation. For the general case, we define exponential classes of multi-period variable upper bound and multi-period ramping inequalities, and give conditions under which these inequalities define facets of ramping polyhedra. Finally, we present exact polynomial separation algorithms formore » the inequalities and report computational experiments on using them in a branch-and-cut algorithm to solve unit commitment problems in power generation.« less

  7. Evaluation of temporary ramp metering for work zones.

    DOT National Transportation Integrated Search

    2012-11-01

    Ramp metering has been successfully implemented in many states to improve traffic operations on freeways. Studies have documented the positive mobility and safety benefits of ramp metering. However, there have been no studies on the use of ramp meter...

  8. Hall effects on unsteady MHD flow of second grade fluid through porous medium with ramped wall temperature and ramped surface concentration

    NASA Astrophysics Data System (ADS)

    VeeraKrishna, M.; Chamkha, Ali J.

    2018-05-01

    The heat generation/absorption and thermo-diffusion on an unsteady free convective MHD flow of radiating and chemically reactive second grade fluid near an infinite vertical plate through a porous medium and taking the Hall current into account have been studied. Assume that the bounding plate has a ramped temperature with a ramped surface concentration and isothermal temperature with a ramped surface concentration. The analytical solutions for the governing equations are obtained by making use of the Laplace transforms technique. The velocity, temperature, and concentration profiles are discussed through graphs. We also found that velocity, temperature, and concentration profiles in the case of ramped temperature with ramped surface concentrations are less than those of isothermal temperature with ramped surface concentrations. Also, the expressions of the skin friction, Nusselt number, and Sherwood number are obtained and represented computationally through a tabular form.

  9. Tamping Ramping: Algorithmic, Implementational, and Computational Explanations of Phasic Dopamine Signals in the Accumbens

    PubMed Central

    Lloyd, Kevin; Dayan, Peter

    2015-01-01

    Substantial evidence suggests that the phasic activity of dopamine neurons represents reinforcement learning’s temporal difference prediction error. However, recent reports of ramp-like increases in dopamine concentration in the striatum when animals are about to act, or are about to reach rewards, appear to pose a challenge to established thinking. This is because the implied activity is persistently predictable by preceding stimuli, and so cannot arise as this sort of prediction error. Here, we explore three possible accounts of such ramping signals: (a) the resolution of uncertainty about the timing of action; (b) the direct influence of dopamine over mechanisms associated with making choices; and (c) a new model of discounted vigour. Collectively, these suggest that dopamine ramps may be explained, with only minor disturbance, by standard theoretical ideas, though urgent questions remain regarding their proximal cause. We suggest experimental approaches to disentangling which of the proposed mechanisms are responsible for dopamine ramps. PMID:26699940

  10. Launch of a Vehicle from a Ramp

    ERIC Educational Resources Information Center

    Cross, Rod

    2011-01-01

    A vehicle proceeding up an inclined ramp will become airborne if the ramp comes to a sudden end and if the vehicle fails to stop before it reaches the end of the ramp. A vehicle may also become airborne if it passes over the top of a hill at sufficient speed. In both cases, the vehicle becomes airborne if the point of support underneath the…

  11. Modified Protein Improves Vitiligo Symptoms in Mice

    MedlinePlus

    ... Vitiligo Symptoms in Mice Spotlight on Research Modified Protein Improves Vitiligo Symptoms in Mice By Colleen Labbe, ... D., Ph.D., Rush University. Altering a key protein involved in the development of vitiligo may protect ...

  12. 40 CFR 1033.520 - Alternative ramped modal cycles.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...) Following the completion of the third test phase of the applicable ramped modal cycle, conduct the post... POLLUTION CONTROLS CONTROL OF EMISSIONS FROM LOCOMOTIVES Test Procedures § 1033.520 Alternative ramped modal... locomotive notch settings. Ramped modal cycles combine multiple test modes of a discrete-mode steady-state...

  13. Microbial response to modified precipitation patterns in tallgrass prairie soil: molecular mechanisms, activity rates and organic matter dynamics

    NASA Astrophysics Data System (ADS)

    Zeglin, L. H.; David, M.; Bottomley, P.; Hettich, R. L.; Jansson, J.; Jumpponen, A.; Rice, C. W.; Tringe, S.; VerBerkmoes, N. C.; Myrold, D.

    2011-12-01

    A significant amount of carbon (C) is processed and stored in prairie soils: grasslands cover 6.1-7.4% of the earth's land surface and hold 7.3-11.4% of global soil C. Global change models predict that the future precipitation regime across the North American Great Plains will entail less frequent but larger rainfall events. The response of prairie soil microbial C processing and allocation to this scenario of higher hydrologic variability is not known, but will be a key determiner of the future capacity for prairie soil C sequestration. We are approaching this problem by assessing soil microbial function (respiration, C utilization efficiency, extracellular enzyme activity) and molecular indicators of dominant C allocation pathways (soil transcriptome, proteome and metabolome) under ambient and experimentally modified precipitation regimes. The rainfall manipulation plots (RaMPs) at the Konza Prairie Long-Term Ecological Research (LTER) site in eastern Kansas, USA is a replicated field manipulation of the magnitude and frequency of natural precipitation that was established in 1998. We collected soil before, during and after a rainfall event in both ambient and modified precipitation treatments and measured the microbial response. Microbial respiration doubled in both treatments during the water addition, and cellobiohydrolase enzyme potential activity (a catalyst of cellulose hydrolysis) increased slightly, but no significant effect of altered precipitation treatment has emerged. The fungal and bacterial ribosomal gene composition was also similar between precipitation treatments. Although pools of genes and extracellular enzymes may be relatively static during short-term dynamic conditions, transcript and intracellular protein abundances may be more indicative of the active microbial metabolic response to rapid shifts in soil moisture. Thus, analysis of transcript and protein composition is underway. In addition, we have implemented a series of lab experiments

  14. pH-Sensitive fusogenic polymer-modified liposomes as a carrier of antigenic proteins for activation of cellular immunity.

    PubMed

    Yuba, Eiji; Kojima, Chie; Harada, Atsushi; Tana; Watarai, Shinobu; Kono, Kenji

    2010-02-01

    By modification of liposomes with poly(glycidol) derivatives such as succinylated poly(glycidol) and 3-methylglutarylated poly(glycidol), we have developed functional liposomes that generate fusion ability at mildly acidic pH. We investigated the feasibility of these polymer-modified liposomes as a carrier of antigenic proteins for induction of cellular immunity. These pH-sensitive fusogenic liposomes encapsulating ovalbumin (OVA) were applied to DC2.4 cells, a murine dendritic cell line. Observation with confocal laser scanning microscopy showed that these polymer-modified liposomes were taken up efficiently by the cells, thereafter delivering their contents into the cytosol, probably through fusion with endosomal membranes. Murine bone marrow-derived dendritic cells treated with polymer-modified liposomes encapsulating OVA stimulated CD8-OVA1.3 cells more strongly than OT4H.1D5 cells, indicating that the liposomes induced MHC class I-restricted presentation. Furthermore, administration of the polymer-modified, OVA-loaded liposomes from nasal cavities of mice induced stronger cellular immune responses than the OVA-loaded plain liposomes. Because the ability of the polymer-modified liposomes to activate cellular immunity was comparable to that of Freund's complete adjuvant, which is a widely used adjuvant, they potentially have use in production of efficient vaccines for immunotherapy.

  15. Early Observations with the ACS Ramp Filters

    NASA Astrophysics Data System (ADS)

    Tsvetanov, Z.; Hartig, G.; Bohlin, R.; Tran, H. D.; Martel, A.; Sirianni, M.; Clampin, M.

    2002-05-01

    The Advanced Camera for Surveys (ACS) on-board the Hubble Space Telescope (HST) is equipped with a set of ramp filters which provide imaging capability at 2% and 9% bandwidth in the range 3700-10700 Å. Each ramp filter consist of three segments where the middle segment can be used with both the Wide Field Channel (WFC) and High Resolution Channel (HRC), while the inner and outer segments can be used only with WFC. The monochromatic field of view is approximately 40'' by 80''. We will present observations of the planetary nebula (PN) NGC6543 (the Cat's Eye) taken with the ACS ramp filetrs in several key emission lines - [O II] 3727, [O III] 5007, H-alpha+[N II], and [S II] 6725. These four emission lines fall onto three separate middle ramp segments - FR388N, FR505N, and FR656N - and will allow inter-comparison between the ACS ramp filters and fixed bandpass narrow-band filters F502N and F658N for both the WFC and HRC detectors. These observations were taken as part of the HST Servicing Mission Orbital Verification program and were designed to test ramp filters performance. We will demostrate our ability to obtain monochromatic (i.e., emission line) images at arbitrary wavelength and recover the surface brightness distribution. This work was supported by a NASA contract and a NASA grant.

  16. Gc protein (vitamin D-binding protein): Gc genotyping and GcMAF precursor activity.

    PubMed

    Nagasawa, Hideko; Uto, Yoshihiro; Sasaki, Hideyuki; Okamura, Natsuko; Murakami, Aya; Kubo, Shinichi; Kirk, Kenneth L; Hori, Hitoshi

    2005-01-01

    The Gc protein (human group-specific component (Gc), a vitamin D-binding protein or Gc globulin), has important physiological functions that include involvement in vitamin D transport and storage, scavenging of extracellular G-actin, enhancement of the chemotactic activity of C5a for neutrophils in inflammation and macrophage activation (mediated by a GalNAc-modified Gc protein (GcMAF)). In this review, the structure and function of the Gc protein is focused on especially with regard to Gc genotyping and GcMAF precursor activity. A discussion of the research strategy "GcMAF as a target for drug discovery" is included, based on our own research.

  17. Preparation and evaluation of tara-modified proteins

    USDA-ARS?s Scientific Manuscript database

    Quebracho, a vegetable tannin, can be used to modify gelatin to produce a product that has been applied effectively as a filler in leather processing, as described in our previous report. In this ongoing study, another vegetable tannin tara is examined for its possible application in protein modifi...

  18. Ramp Technology and Intelligent Processing in Small Manufacturing

    NASA Technical Reports Server (NTRS)

    Rentz, Richard E.

    1992-01-01

    To address the issues of excessive inventories and increasing procurement lead times, the Navy is actively pursuing flexible computer integrated manufacturing (FCIM) technologies, integrated by communication networks to respond rapidly to its requirements for parts. The Rapid Acquisition of Manufactured Parts (RAMP) program, initiated in 1986, is an integral part of this effort. The RAMP program's goal is to reduce the current average production lead times experienced by the Navy's inventory control points by a factor of 90 percent. The manufacturing engineering component of the RAMP architecture utilizes an intelligent processing technology built around a knowledge-based shell provided by ICAD, Inc. Rules and data bases in the software simulate an expert manufacturing planner's knowledge of shop processes and equipment. This expert system can use Product Data Exchange using STEP (PDES) data to determine what features the required part has, what material is required to manufacture it, what machines and tools are needed, and how the part should be held (fixtured) for machining, among other factors. The program's rule base then indicates, for example, how to make each feature, in what order to make it, and to which machines on the shop floor the part should be routed for processing. This information becomes part of the shop work order. The process planning function under RAMP greatly reduces the time and effort required to complete a process plan. Since the PDES file that drives the intelligent processing is 100 percent complete and accurate to start with, the potential for costly errors is greatly diminished.

  19. Ramp technology and intelligent processing in small manufacturing

    NASA Astrophysics Data System (ADS)

    Rentz, Richard E.

    1992-04-01

    To address the issues of excessive inventories and increasing procurement lead times, the Navy is actively pursuing flexible computer integrated manufacturing (FCIM) technologies, integrated by communication networks to respond rapidly to its requirements for parts. The Rapid Acquisition of Manufactured Parts (RAMP) program, initiated in 1986, is an integral part of this effort. The RAMP program's goal is to reduce the current average production lead times experienced by the Navy's inventory control points by a factor of 90 percent. The manufacturing engineering component of the RAMP architecture utilizes an intelligent processing technology built around a knowledge-based shell provided by ICAD, Inc. Rules and data bases in the software simulate an expert manufacturing planner's knowledge of shop processes and equipment. This expert system can use Product Data Exchange using STEP (PDES) data to determine what features the required part has, what material is required to manufacture it, what machines and tools are needed, and how the part should be held (fixtured) for machining, among other factors. The program's rule base then indicates, for example, how to make each feature, in what order to make it, and to which machines on the shop floor the part should be routed for processing. This information becomes part of the shop work order. The process planning function under RAMP greatly reduces the time and effort required to complete a process plan. Since the PDES file that drives the intelligent processing is 100 percent complete and accurate to start with, the potential for costly errors is greatly diminished.

  20. Ramp compression of a metallic liner driven by a shaped 5 MA current on the SPHINX machine

    NASA Astrophysics Data System (ADS)

    D'Almeida, Thierry; Lassalle, Francis; Morell, Alain; Grunenwald, Julien; Zucchini, Frédéric; Loyen, Arnaud; Maysonnave, Thomas; Chuvatin, Alexandre

    2013-06-01

    SPHINX is a 6MA, 1- μs Linear Transformer Driver operated by the CEA Gramat (France) and primarily used for imploding Z-pinch loads for radiation effects studies. Among the options that are currently being considered for improving the generator performances, there is a compact Dynamic Load Current Amplifier (DLCM). A method for performing magnetic ramp compression experiments, without modifying the generator operation scheme, was developed using the DLCM to shape the initial current pulse. We present the overall experimental configuration chosen for these experiments, based on electrical and hydrodynamic simulations. Initial results obtained over a set of experiments on an aluminum cylindrical liner, ramp-compressed to a peak pressure of 23 GPa, are presented. Details of the electrical and Photonic Doppler Velocimetry (PDV) setups used to monitor and diagnose the ramp compression experiments are provided. Current profiles measured at various locations across the system, particularly the load current, agree with simulated current profile and demonstrate adequate pulse shaping by the DLCM. The liner inner free surface velocity measurements agree with the hydrocode results obtained using the measured load current as the input. Higher ramp pressure levels are foreseen in future experiments with an improved DLCM system.

  1. Viral delivery of genome-modifying proteins for cellular reprogramming.

    PubMed

    Mikkelsen, Jacob Giehm

    2018-06-18

    Following the successful development of virus-based gene vehicles for genetic therapies, exploitation of viruses as carriers of genetic tools for cellular reprogramming and genome editing should be right up the street. However, whereas persistent, potentially life-long gene expression is the main goal of conventional genetic therapies, tools and bits for genome engineering should ideally be short-lived and active only for a limited time. Although viral vector systems have already been adapted for potent genome editing both in vitro and in vivo, regulatable gene expression systems or self-limiting expression circuits need to be implemented limiting exposure of chromatin to genome-modifying enzymes. As an alternative approach, emerging virus-based protein delivery technologies support direct protein delivery, providing a short, robust boost of enzymatic activity in transduced cells. Is this potentially the perfect way of shipping loads of cargo to many recipients and still maintain short-term activity? Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Comprehensive School Counseling Programs and Student Achievement Outcomes: A Comparative Analysis of Ramp versus Non-Ramp Schools

    ERIC Educational Resources Information Center

    Wilkerson, Kevin; Perusse, Rachelle; Hughes, Ashley

    2013-01-01

    This study compares school-wide Annual Yearly Progress (AYP) results in Indiana schools earning the Recognized ASCA Model Program (RAMP) designation (n = 75) with a sample of control schools stratified by level and locale (n = 226). K-12 schools earning the RAMP designation in 2007, 2008, and 2009 comprise the experimental group. Findings indicate…

  3. International Union of Pharmacology. XXXII. The mammalian calcitonin gene-related peptides, adrenomedullin, amylin, and calcitonin receptors.

    PubMed

    Poyner, David R; Sexton, Patrick M; Marshall, Ian; Smith, David M; Quirion, Remi; Born, Walter; Muff, Roman; Fischer, Jan A; Foord, Steven M

    2002-06-01

    The calcitonin family of peptides comprises calcitonin, amylin, two calcitonin gene-related peptides (CGRPs), and adrenomedullin. The first calcitonin receptor was cloned in 1991. Its pharmacology is complicated by the existence of several splice variants. The receptors for the other members the family are made up of subunits. The calcitonin-like receptor (CL receptor) requires a single transmembrane domain protein, termed receptor activity modifying protein, RAMP1, to function as a CGRP receptor. RAMP2 and -3 enable the same CL receptor to behave as an adrenomedullin receptor. Although the calcitonin receptor does not require RAMP to bind and respond to calcitonin, it can associate with the RAMPs, resulting in a series of receptors that typically have high affinity for amylin and varied affinity for CGRP. This review aims to reconcile what is observed when the receptors are reconstituted in vitro with the properties they show in native cells and tissues. Experimental conditions must be rigorously controlled because different degrees of protein expression may markedly modify pharmacology in such a complex situation. Recommendations, which follow International Union of Pharmacology guidelines, are made for the nomenclature of these multimeric receptors.

  4. Twin Cities ramp meter evaluation : evaluation plan

    DOT National Transportation Integrated Search

    2000-09-25

    The Minnesota Department of Transportation (Mn/DOT) uses ramp meters to manage freeway access on approximately 210 miles of freeways in the Twin Cities metropolitan area. Mn/DOT first tested ramp meters in 1969 as a method to optimize freeway safety ...

  5. Twin Cities ramp meter evaluation : executive summary

    DOT National Transportation Integrated Search

    2001-02-01

    This report details the results of a study on the traffic flow and safety impacts of ramp metering. The study served two important public purposes. 1. It thoroughly documented the benefits resulting from ramp metering to traffic operations and relate...

  6. Study on Trailing Edge Ramp of Supercritical Airfoil

    DTIC Science & Technology

    2016-03-30

    7 th Asia-Pacific International Symposium on Aerospace Technology, 25 – 27 November 2015, Cairns Study on Trailing Edge Ramp of Supercritical...China Abstract Trailing edge flow control method could improve the performance of supercritical airfoil with a small modification on the original...airfoil. In this paper, a ramp of 2%~7% chord length is sliced near the trailing edge to improve airfoil performance. The trailing edge ramp is

  7. Ramp metering : a review of the literature.

    DOT National Transportation Integrated Search

    1998-01-01

    Ramp metering is an effective, viable, and practical strategy used to manage freeway traffic. It is a proven freeway management technique as various forms of ramp control have been in place since the 1960s in the Chicago, Detroit, and Los Angeles are...

  8. Lateral ramps in the folded Appalachians and in overthrust belts worldwide; a fundamental element of thrust-belt architecture

    USGS Publications Warehouse

    Pohn, Howard A.

    2000-01-01

    Lateral ramps are zones where decollements change stratigraphic level along strike; they differ from frontal ramps, which are zones where decollements change stratigraphic level perpendicular to strike. In the Appalachian Mountains, the surface criteria for recognizing the subsurface presence of lateral ramps include (1) an abrupt change in wavelength or a termination of folds along strike, (2) a conspicuous change in the frequency of mapped faults or disturbed zones (extremely disrupted duplexes) at the surface, (3) long, straight river trends emerging onto the coastal plain or into the Appalachian Plateaus province, (4) major geomorphic discontinuities in the trend of the Blue Ridge province, (5) interruption of Mesozoic basins by cross-strike border faults, and (6) zones of modern and probable ancient seismic activity. Additional features related to lateral ramps include tectonic windows, cross-strike igneous intrusions, areas of giant landslides, and abrupt changes in Paleozoic sedimentation along strike. Proprietary strike-line seismic-reflection profiles cross three of the lateral ramps that were identified by using the surface criteria. The profiles confirm their presence and show their detailed nature in the subsurface. Like frontal ramps, lateral ramps are one of two possible consequences of fold-and-thrust-belt tectonics and are common elements in the Appalachian fold-and-thrust belt. A survey of other thrust belts in the United States and elsewhere strongly suggests that lateral ramps at depth can be identified by their surface effects. Lateral ramps probably are the result of thrust sheet motion caused by continued activation of ancient cratonic fracture systems. Such fractures localized the transform faults along which the continental segments adjusted during episodes of sea-floor spreading.

  9. F-15 HiDEC taxi on ramp at sunrise

    NASA Image and Video Library

    1991-09-23

    NASA's highly modified F-15A (Serial #71-0287) used for digital electronic flight and engine control systems research, at sunrise on the ramp at the Dryden Flight Research Facility, Edwards, California. The F-15 was called the HIDEC (Highly Integrated Digital Electronic Control) flight facility. Research programs flown on the testbed vehicle have demonstrated improved rates of climb, fuel savings, and engine thrust by optimizing systems performance. The aircraft also tested and evaluated a computerized self-repairing flight control system for the Air Force that detects damaged or failed flight control surfaces. The system then reconfigures undamaged control surfaces so the mission can continue or the aircraft is landed safely.

  10. Fabrication of interface-modified ramp-edge junction on YBCO ground plane with multilayer structure

    NASA Astrophysics Data System (ADS)

    Wakana, H.; Adachi, S.; Kamitani, A.; Sugiyama, H.; Sugano, T.; Horibe, M.; Ishimaru, Y.; Tarutani, Y.; Tanabe, K.

    2003-10-01

    We examined the fabrication conditions to obtain high-quality ramp-edge Josephson junctions on a liquid-phase-epitaxy YBa 2Cu 3O y (LPE-YBCO) ground plane, in particular, focusing on the fabrication of a suitable insulating layer on the ground plane and the post-annealing conditions to load oxygen to the ground plane. A (LaAlO 3) 0.3-(SrAl 0.5Ta 0.5O 3) 0.7 (LSAT) insulating film on the ground planes exhibited a conductance ranging from 10 -4 to 10 -8 S after deposition of an upper superconducting film, suggesting existence of some leak paths through the LSAT insulating layer. By introducing approximately 30 nm thick SrTiO 3 (STO) buffer layers on both side of the LSAT insulating layer. We reproducibly obtained a conductance lower than 10 -8 S. The dielectric constant of the STO/LSAT/STO layer was 32, which was slightly larger than that of the single LSAT layer. It was found that a very slow cooling rate of 1.0 °C/h in oxygen was needed to fully oxidize the ground plane through the STO/LSAT/STO insulating layers, while the oxidation time could be effectively reduced by introducing via holes in the insulating layer at an interval of 200 μm. Ramp-edge junctions on LPE-YBCO ground planes with STO/LSAT/STO insulating layers exhibited a 1 σ-spread in Ic of 8% for 100-junction series-arrays and a sheet inductance of 0.7 pH/□ at 4.2 K.

  11. Synthesis and structural characterization of carboxyethylpyrrole-modified proteins: mediators of age-related macular degeneration.

    PubMed

    Lu, Liang; Gu, Xiaorong; Hong, Li; Laird, James; Jaffe, Keeve; Choi, Jaewoo; Crabb, John; Salomon, Robert G

    2009-11-01

    Protein modifications in which the epsilon-amino group of lysyl residues is incorporated into a 2-(omega-carboxyethyl)pyrrole (CEP) are mediators of age-related macular degeneration (AMD). They promote both angiogenesis into the retina ('wet AMD') and geographic retinal atrophy ('dry AMD'). Blood levels of CEPs are biomarkers for clinical prognosis of the disease. To enable mechanistic studies of their role in promoting AMD, for example, through the activation of B- and T-cells, interaction with receptors, or binding with complement proteins, we developed an efficient synthesis of CEP derivatives, that is especially effective for proteins. The structures of tryptic peptides derived from CEP-modified proteins were also determined. A key finding is that 4,7-dioxoheptanoic acid 9-fluorenylmethyl ester reacts with primary amines to provide 9-fluorenylmethyl esters of CEP-modified proteins that can be deprotected in situ with 1,8-diazabicyclo[5.4.0]undec-7-ene without causing protein denaturation. The introduction of multiple CEP-modifications with a wide variety of CEP:protein ratios is readily achieved using this strategy.

  12. Identification of a chitinase modifying protein from Fusarium verticillioides: truncation of a host resistance protein by a fungalysin metalloprotease

    USDA-ARS?s Scientific Manuscript database

    Chitinase modifying proteins (cmps) are proteases, secreted by fungal pathogens, which truncate the plant class IV chitinases ChitA and ChitB during maize ear rot. Cmp activity has been characterized for Bipolaris zeicola and Stenocarpella maydis, but the identities of the proteases are not known. H...

  13. Systemic activation of NF-κB driven luciferase activity in transgenic mice fed advanced glycation end products modified albumin.

    PubMed

    Nass, Norbert; Bayreuther, Kristina; Simm, Andreas

    2017-04-01

    Advanced glycation end products (AGEs) are stable end products of the Maillard reaction and accumulate with progressing ageing and degenerative diseases. Significant amounts of AGE-modified peptides are also consumed with processed food. AGEs bind to specific receptors, especially the receptor of AGEs (RAGE). Activation of RAGE then evokes intracellular signalling, finally resulting in the activation of the NF-κB transcription factor and therefore a proinflammatory state. We here analysed, whether NF-κB is activated in short term upon feeding an AGE-modified protein in-vivo. Transgenic mice expressing firefly luciferase under the control of an NF-κB responsive promoter were intraperitoneally injected or fed with AGE-modified- or control albumin and luciferase expression was analysed by in-vivo imaging and by in-vitro by determination of luciferase enzyme activity in heart, lung, gut, spleen, liver and kidney. In all organs, an activation of the luciferase reporter gene was observed in response to AGE-BSA feeding, however with different intensity and timing. The gut exhibited highest luciferase activity and this activity peaked 6-8 h post AGE-feeding. In heart and kidney, luciferase activity increased for up to 12 h post feeding. All other organs tested, exhibited highest activity at 10 h after AGE-consumption. Altogether, these data demonstrate that feeding AGE-modified protein resulted in a transient and systemic activation of the NF-κB reporter.

  14. Shock-Ramp Loading of Tin and Aluminum

    NASA Astrophysics Data System (ADS)

    Seagle, Christopher; Davis, Jean; Martin, Matthew; Hanshaw, Heath

    2013-06-01

    Equation of state properties for materials off the principle Hugoniot and isentrope are currently poorly constrained. The ability to directly probe regions of phase space between the Hugoniot and isentrope under dynamic loading will greatly improve our ability to constrain equation of state properties under a variety of conditions and study otherwise inaccessible phase transitions. We have developed a technique at Sandia's Z accelerator to send a steady shock wave through a material under test, and subsequently ramp compress from the Hugoniot state. The shock-ramp experimental platform results in a unique loading path and enables probing of equation of state properties in regions of phase space otherwise difficult to access in dynamic experiments. A two-point minimization technique has been developed for the analysis of shock-ramp velocity data. The technique correctly accounts for the ``initial'' Hugoniot density of the material under test before the ramp wave arrives. Elevated quasi-isentropes have been measured for solid aluminum up to 1.4 Mbar and liquid tin up to 1.1 Mbar using the shock ramp technique. These experiments and the analysis of the resulting velocity profiles will be discussed. Sandia National Laboratories is a multi-program laboratory operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85.

  15. DNA-modified electrodes fabricated using copper-free click chemistry for enhanced protein detection.

    PubMed

    Furst, Ariel L; Hill, Michael G; Barton, Jacqueline K

    2013-12-31

    A method of DNA monolayer formation has been developed using copper-free click chemistry that yields enhanced surface homogeneity and enables variation in the amount of DNA assembled; extremely low-density DNA monolayers, with as little as 5% of the monolayer being DNA, have been formed. These DNA-modified electrodes (DMEs) were characterized visually, with AFM, and electrochemically, and were found to facilitate DNA-mediated reduction of a distally bound redox probe. These low-density monolayers were found to be more homogeneous than traditional thiol-modified DNA monolayers, with greater helix accessibility through an increased surface area-to-volume ratio. Protein binding efficiency of the transcriptional activator TATA-binding protein (TBP) was also investigated on these surfaces and compared to that on DNA monolayers formed with standard thiol-modified DNA. Our low-density monolayers were found to be extremely sensitive to TBP binding, with a signal decrease in excess of 75% for 150 nM protein. This protein was detectable at 4 nM, on the order of its dissociation constant, with our low-density monolayers. The improved DNA helix accessibility and sensitivity of our low-density DNA monolayers to TBP binding reflects the general utility of this method of DNA monolayer formation for DNA-based electrochemical sensor development.

  16. A modified Poisson-Boltzmann equation applied to protein adsorption.

    PubMed

    Gama, Marlon de Souza; Santos, Mirella Simões; Lima, Eduardo Rocha de Almeida; Tavares, Frederico Wanderley; Barreto, Amaro Gomes Barreto

    2018-01-05

    Ion-exchange chromatography has been widely used as a standard process in purification and analysis of protein, based on the electrostatic interaction between the protein and the stationary phase. Through the years, several approaches are used to improve the thermodynamic description of colloidal particle-surface interaction systems, however there are still a lot of gaps specifically when describing the behavior of protein adsorption. Here, we present an improved methodology for predicting the adsorption equilibrium constant by solving the modified Poisson-Boltzmann (PB) equation in bispherical coordinates. By including dispersion interactions between ions and protein, and between ions and surface, the modified PB equation used can describe the Hofmeister effects. We solve the modified Poisson-Boltzmann equation to calculate the protein-surface potential of mean force, treated as spherical colloid-plate system, as a function of process variables. From the potential of mean force, the Henry constants of adsorption, for different proteins and surfaces, are calculated as a function of pH, salt concentration, salt type, and temperature. The obtained Henry constants are compared with experimental data for several isotherms showing excellent agreement. We have also performed a sensitivity analysis to verify the behavior of different kind of salts and the Hofmeister effects. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Interrogating Protein Phosphatases with Chemical Activity Probes.

    PubMed

    Casey, Garrett R; Stains, Cliff I

    2018-06-04

    Protein phosphatases, while long overlooked, have recently become appreciated as drivers of both normal- and disease-associated signaling events. As a result, the spotlight is now turning torwards this enzyme family and efforts geared towards the development of modern chemical tools for studying these enzymes are well underway. This Minireview focuses on the evolution of chemical activity probes, both optical and covalent, for the study of protein phosphatases. Small-molecule probes, global monitoring of phosphatase activity through the use of covalent modifiers, and targeted fluorescence-based activity probes are discussed. We conclude with an overview of open questions in the field and highlight the potential impact of chemical tools for studying protein phosphatases. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. 3. Ramp No. 6 connection between Medical Detachment Barracks: Building ...

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

    3. Ramp No. 6 connection between Medical Detachment Barracks: Building Nos. 9970-B (left) and 9969-B (right). The many windows makes this section almost unique among the ramps and corridors. - Madigan Hospital, Corridors & Ramps, Bounded by Wilson & McKinley Avenues & Garfield & Lincoln Streets, Tacoma, Pierce County, WA

  19. Allergenicity, trypsin inhibitor activity and nutritive quality of enzymatically modified soy proteins.

    PubMed

    De La Barca, Ana María Calderón; Wall, Abraham; López-Díaz, José Alberto

    2005-05-01

    Two ultrafiltered soy flour protein fractions were evaluated; the first was obtained by hydrolysis (0.5-3 kDa, F(0.5-3)), and the second was an enzymatically methionine-enriched fraction (1-10 kDa, F(1-10)E). Amino acid profiles, protein quality, allergenicity (against soy-sensitive infant sera) and trypsin inhibitor activity were determined. Fraction F(1-10)E fulfilled amino acid requirements for infants, whereas the F(0.5-3) fraction was methionine deficient. Both fractions were similar in net protein utilization, and F(1-10)E digestibility was comparable with casein and higher (P?activity with respect to soy flour was 8.1%, 3.3% and 1% for hydrolysate, F(1-10)E and F(0.5-3), respectively. Both fractions presented high nutritive quality and reduced or null allergenicity. The trypsin inhibitor activity decreased along processing and could be a useful indicator for production of hypoallergenic proteins.

  20. Using archived ITS data to measure the operational benefits of a system-wide adaptive ramp metering system : appendix online\\0x20106: OR\\0x2010217 NB time-space speed contour plots with meter activations.

    DOT National Transportation Integrated Search

    2008-12-01

    Programmable logic controllers (PLCs) were installed at several key ramps with the assistance of the City of Portland and used to capture additional data about ramp operations that are not otherwise logged. The data include include the activation and...

  1. The calcium-sensing receptor and its interacting proteins

    PubMed Central

    Huang, Chunfa; Miller, R Tyler

    2007-01-01

    Abstract Seven membrane-spanning, or G protein-coupled receptors were originally thought to act through het-erotrimeric G proteins that in turn activate intracellular enzymes or ion channels, creating relatively simple, linear signalling pathways. Although this basic model remains true in that this family does act via a relatively small number of G proteins, these signalling systems are considerably more complex because the receptors interact with or are located near additional proteins that are often unique to a receptor or subset of receptors. These additional proteins give receptors their unique signalling ‘personalities’. The extracellular Ca-sensing receptor (CaR) signals via Gαi, Gαq and Gα12/13, but its effects in vivo demonstrate that the signalling pathways controlled by these subunits are not sufficient to explain all its biologic effects. Additional structural or signalling proteins that interact with the CaR may explain its behaviour more fully. Although the CaR is less well studied in this respect than other receptors, several CaR-interacting proteins such as filamin, a potential scaffolding protein, receptor activity modifying proteins (RAMPs) and potassium channels may contribute to the unique characteristics of the CaR. The CaR also appears to interact with additional proteins common to other G protein-coupled receptors such as arrestins, G protein receptor kinases, protein kinase C, caveolin and proteins in the ubiquitination pathway. These proteins probably represent a few initial members of CaR-based signalling complex. These and other proteins may not all be associated with the CaR in all tissues, but they form the basis for understanding the complete nature of CaR signalling. PMID:17979874

  2. Characterizing and analyzing ramping events in wind power, solar power, load, and netload

    DOE PAGES

    Cui, Mingjian; Zhang, Jie; Feng, Cong; ...

    2017-04-07

    Here, one of the biggest concerns associated with integrating a large amount of renewable energy into the power grid is the ability to handle large ramps in the renewable power output. For the sake of system reliability and economics, it is essential for power system operators to better understand the ramping features of renewable, load, and netload. An optimized swinging door algorithm (OpSDA) is used and extended to accurately and efficiently detect ramping events. For wind power ramps detection, a process of merging 'bumps' (that have a different changing direction) into adjacent ramping segments is included to improve the performancemore » of the OpSDA method. For solar ramps detection, ramping events that occur in both clear-sky and measured (or forecasted) solar power are removed to account for the diurnal pattern of solar generation. Ramping features are extracted and extensively compared between load and netload under different renewable penetration levels (9.77%, 15.85%, and 51.38%). Comparison results show that (i) netload ramp events with shorter durations and smaller magnitudes occur more frequently when renewable penetration level increases, and the total number of ramping events also increases; and (ii) different ramping characteristics are observed in load and netload even with a low renewable penetration level.« less

  3. Bacterial expression and purification of a heterodimeric adrenomedullin receptor extracellular domain complex using DsbC-assisted disulfide shuffling.

    PubMed

    Hill, Heather E; Pioszak, Augen A

    2013-03-01

    Adrenomedullin (AM) is a peptide hormone that is a potent vasodilator and is essential for vascular development. The AM receptor is a heterodimeric cell surface receptor composed of the calcitonin receptor-like receptor (CLR), a class B G protein-coupled receptor, in association with either of two receptor activity modifying protein (RAMP) coreceptors, RAMP2 or -3. The extracellular domains (ECDs) of CLR and the RAMPs form the primary AM binding site. Here, we present novel methodology for expression and purification of a heterodimeric AM receptor ECD complex as an MBP-CLR ECD fusion protein in association with the RAMP2 ECD. Co-expression of the RAMP2 ECD with the disulfide bond isomerase DsbC in the oxidizing cytoplasm of E. coli trxB gor enabled proper disulfide formation in vivo. The isolated RAMP2 ECD was purified to homogeneity. Co-expression of a soluble MBP-CLR ECD fusion protein with DsbC in E. coli trxB gor yielded a heterogeneous mixture of species with misfolded ECD. Incubation of affinity-purified MBP-CLR ECD in vitro with purified RAMP2 ECD, DsbC, and glutathione redox buffer promoted proper folding of the CLR ECD and formation of a stable MBP-CLR ECD:RAMP2 ECD complex that was purified by size-exclusion chromatography and which exhibited specific AM binding. Approximately 40mg of highly purified complex was obtained starting with 6L bacterial cultures for each protein. The methodology reported here will facilitate structure/function studies of the AM receptor. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Modeling the evolution of a ramp-flat-ramp thrust system: A geological application of DynEarthSol2D

    NASA Astrophysics Data System (ADS)

    Feng, L.; Choi, E.; Bartholomew, M. J.

    2013-12-01

    DynEarthSol2D (available at http://bitbucket.org/tan2/dynearthsol2) is a robust, adaptive, two-dimensional finite element code that solves the momentum balance and the heat equation in Lagrangian form using unstructured meshes. Verified in a number of benchmark problems, this solver uses contingent mesh adaptivity in places where shear strain is focused (localization) and a conservative mapping assisted by marker particles to preserve phase and facies boundaries during remeshing. We apply this cutting-edge geodynamic modeling tool to the evolution of a thrust fault with a ramp-flat-ramp geometry. The overall geometry of the fault is constrained by observations in the northern part of the southern Appalachian fold and thrust belt. Brittle crust is treated as a Mohr-Coulomb plastic material. The thrust fault is a zone of a finite thickness but has a lower cohesion and friction angle than its surrounding rocks. When an intervening flat separates two distinct sequential ramps crossing different stratigraphic intervals, the thrust system will experience more complex deformations than those from a single thrust fault ramp. The resultant deformations associated with sequential ramps would exhibit a spectrum of styles, of which two end members correspond to ';overprinting' and ';interference'. Reproducing these end-member styles as well as intermediate ones, our models show that the relative importance of overprinting versus interference is a sensitive function of initial fault geometry and hanging wall displacement. We further present stress and strain histories extracted from the models. If clearly distinguishable, they will guide the interpretation of field observations on thrust faults.

  5. Ramp compression of magnesium oxide to 234 GPa

    DOE PAGES

    Wang, Jue; Smith, R. F.; Coppari, F.; ...

    2014-05-07

    Single-crystal magnesium oxide (MgO) samples were ramp compressed to above 200 GPa pressure at the Omega laser facility. Multi-stepped MgO targets were prepared using lithography and wet etching techniques. Free surface velocities of ramp-compressed MgO were measured with a VISAR. The sound velocity and stress-density response were determined using an iterative Lagrangian analysis. The measured equation of state is consistent with expectations from previous shock and static data as well as with a recent X-ray diffraction measurement under ramp loading. The peak elastic stresses observed in our samples had amplitudes of 3-5.5 GPa, decreasing with propagation distance.

  6. Ramp-related incidents involving wheeled mobility device users during transit bus boarding/alighting.

    PubMed

    Frost, Karen L; Bertocci, Gina; Smalley, Craig

    2015-05-01

    To estimate the prevalence of wheeled mobility device (WhMD) ramp-related incidents while boarding/alighting a public transit bus and to determine whether the frequency of incidents is less when the ramp slope meets the proposed Americans with Disabilities Act (ADA) maximum allowable limit of ≤9.5°. Observational study. Community public transportation. WhMD users (N=414) accessing a public transit bus equipped with an instrumented ramp. Not applicable. Prevalence of boarding/alighting incidents involving WhMD users and associated ramp slopes; factors affecting incidents. A total of 4.6% (n=35) of WhMD users experienced an incident while boarding/alighting a transit bus. Significantly more incidents occurred during boarding (6.3%, n=26) than during alighting (2.2%, n=9) (P<.01), and when the ramp was deployed to street level (mean slope=11.4°) compared with sidewalk level (mean slope=4.2°) (P=.01). The odds ratio for experiencing an incident when the ramp slope exceeded the proposed ADA maximum allowable ramp slope was 5.4 (95% confidence interval, 2.4-12.2; P<.01). The odds ratio for assistance being rendered to board/alight when the ramp slope exceeded the proposed ADA maximum allowable ramp slope was 5.1 (95% confidence interval, 2.9-9.0; P<.01). The findings of this study support the proposed ADA maximum allowable ramp slope of 9.5°. Ramp slopes >9.5° and ramps deployed to street level are associated with a higher frequency of incidents and provision of assistance. Transit agencies should increase awareness among bus operators of the effect kneeling and deployment location (street/sidewalk) have on the ramp slope. In addition, ramp components and the built environment may contribute to incidents. When prescribing WhMDs, skills training must include ascending/descending ramps at slopes encountered during boarding/alighting to ensure safe and independent access to public transit buses. Copyright © 2015 American Congress of Rehabilitation Medicine

  7. Activation of extrasynaptic, but not synaptic, NMDA receptors modifies amyloid precursor protein expression pattern and increases amyloid-ß production.

    PubMed

    Bordji, Karim; Becerril-Ortega, Javier; Nicole, Olivier; Buisson, Alain

    2010-11-24

    Calcium is a key mediator controlling essential neuronal functions depending on electrical activity. Altered neuronal calcium homeostasis affects metabolism of amyloid precursor protein (APP), leading to increased production of β-amyloid (Aβ), and contributing to the initiation of Alzheimer's disease (AD). A linkage between excessive glutamate receptor activation and neuronal Aβ release was established, and recent reports suggest that synaptic and extrasynaptic NMDA receptor (NMDAR) activation may have distinct consequences in plasticity, gene regulation, and neuronal death. Here, we report for the first time that prolonged activation of extrasynaptic NMDAR, but not synaptic NMDAR, dramatically increased the neuronal production of Aβ. This effect was preceded by a shift from APP695 to Kunitz protease inhibitory domain (KPI) containing APPs (KPI-APPs), isoforms exhibiting an important amyloidogenic potential. Conversely, after synaptic NMDAR activation, we failed to detect any KPI-APP expression and neuronal Aβ production was not modified. Calcium imaging data showed that intracellular calcium concentration after extrasynaptic NMDAR stimulation was lower than after synaptic activation. This suggests distinct signaling pathways for each pool of receptors. We found that modification of neuronal APP expression pattern triggered by extrasynaptic NMDAR activation was regulated at an alternative splicing level involving calcium-/calmodulin-dependent protein kinase IV, but overall APP expression remained identical. Finally, memantine dose-dependently inhibited extrasynaptic NMDAR-induced KPI-APPs expression as well as neuronal Aβ release. Altogether, these data suggest that a chronic activation of extrasynaptic NMDAR promotes amyloidogenic KPI-APP expression leading to neuronal Aβ release, representing a causal risk factor for developing AD.

  8. Mid-crustal detachment and ramp faulting in the Markham Valley, Papua New Guinea

    NASA Astrophysics Data System (ADS)

    Stevens, C.; McCaffrey, R.; Silver, E. A.; Sombo, Z.; English, P.; van der Kevie, J.

    1998-09-01

    Earthquakes and geodetic evidence reveal the presence of a low-angle, mid-crustal detachment fault beneath the Finisterre Range that connects to a steep ramp surfacing near the Ramu-Markham Valley of Papua New Guinea. Waveforms of three large (Mw 6.3 to 6.9) thrust earthquakes that occurred in October 1993 beneath the Finisterre Range 10 to 30 km north of the valley reveal 15° north-dipping thrusts at about 20 km depth. Global Positioning System measurements show up to 20 cm of coseismic slip occurred across the valley, requiring that the active fault extend to within a few hundred meters of the Earth's surface beneath the Markham Valley. Together, these data imply that a gently north-dipping thrust fault in the middle or lower crust beneath the Finisterre Range steepens and shallows southward, forming a ramp fault beneath the north side of the Markham Valley. Waveforms indicate that both the ramp and detachment fault were active during at least one of the earthquakes. While the seismic potential of mid-crustal detachments elsewhere is debated, in Papua New Guinea the detachment fault shows the capability of producing large earthquakes.

  9. Magnetic ramp scale at supercritical perpendicular collisionless shocks: Full particle electromagnetic simulations

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

    Yang, Zhongwei; SOA Key Laboratory for Polar Science, Polar Research Institute of China, Shanghai, 200136; Lu, Quanming

    2013-09-15

    Supercritical perpendicular collisionless shocks are known to exhibit foot, ramp, and overshoot structures. The shock ramp structure is in a smaller scale in contrast to other microstructures (foot and overshoot) within the shock front. One-dimensional full particle simulations of strictly perpendicular shocks over wide ranges of ion beta β{sub i}, Alfvén Mach number M{sub A}, and ion-to-electron mass ratio m{sub i}/m{sub e} are presented to investigate the impact of plasma parameters on the shock ramp scale. Main results are (1) the ramp scale can be as small as several electron inertial length. (2) The simulations suggest that in a regimemore » below the critical ion beta value, the shock front undergoes a periodic self-reformation and the shock ramp scale is time-varying. At higher ion beta values, the shock front self-reformation is smeared. At still higher ion beta value, the motion of reflected ions is quite diffuse so that they can lead to a quasi-steady shock ramp. Throughout the above three conditions, the shock ramp thickness increases with β{sub i}. (3) The increase (decrease) in Mach number and the decrease (increase) in the beta value have almost equivalent impact on the state (i.e., stationary or nonstationary) of the shock ramp. Both of front and ramp thicknesses are increased with M{sub A}.« less

  10. Analysis Balance Parameter of Optimal Ramp metering

    NASA Astrophysics Data System (ADS)

    Li, Y.; Duan, N.; Yang, X.

    2018-05-01

    Ramp metering is a motorway control method to avoid onset congestion through limiting the access of ramp inflows into the main road of the motorway. The optimization model of ramp metering is developed based upon cell transmission model (CTM). With the piecewise linear structure of CTM, the corresponding motorway traffic optimization problem can be formulated as a linear programming (LP) problem. It is known that LP problem can be solved by established solution algorithms such as SIMPLEX or interior-point methods for the global optimal solution. The commercial software (CPLEX) is adopted in this study to solve the LP problem within reasonable computational time. The concept is illustrated through a case study of the United Kingdom M25 Motorway. The optimal solution provides useful insights and guidances on how to manage motorway traffic in order to maximize the corresponding efficiency.

  11. STC1 interference on calcitonin family of receptors signaling during osteoblastogenesis via adenylate cyclase inhibition.

    PubMed

    Terra, Silvia R; Cardoso, João Carlos R; Félix, Rute C; Martins, Leo Anderson M; Souza, Diogo Onofre G; Guma, Fatima C R; Canário, Adelino Vicente M; Schein, Vanessa

    2015-03-05

    Stanniocalcin 1 (STC1) and calcitonin gene-related peptide (CGRP) are involved in bone formation/remodeling. Here we investigate the effects of STC1 on functional heterodimer complex CALCRL/RAMP1, expression and activity during osteoblastogenesis. STC1 did not modify CALCRL and ramp1 gene expression during osteoblastogenesis when compared to controls. However, plasma membrane spatial distribution of CALCRL/RAMP1 was modified in 7-day pre-osteoblasts exposed to either CGRP or STC1, and both peptides induced CALCRL and RAMP1 assembly. CGRP, but not STC1 stimulated cAMP accumulation in 7-day osteoblasts and in CALCRL/RAMP1 transfected HEK293 cells. Furthermore, STC1 inhibited forskolin stimulated cAMP accumulation of HEK293 cells, but not in CALCRL/RAMP1 transfected HEK293 cells. However, STC1 inhibited cAMP accumulation in calcitonin receptor (CTR) HEK293 transfected cells stimulated by calcitonin. In conclusion, STC1 signals through inhibitory G-protein modulates CGRP receptor spatial localization during osteoblastogenesis and may function as a regulatory factor interacting with calcitonin peptide members during bone formation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. Ramp metering : procedure manual.

    DOT National Transportation Integrated Search

    2002-11-01

    Ramp metering is a traffic management tool used to increase the efficiency and safety of the : traffic operations on freeways. It is one of the most cost effective ways of managing traffic flow. : It improves traffic flow on congested freeways and of...

  13. Urea modified cottonseed protein adhesive for wood composite products

    USDA-ARS?s Scientific Manuscript database

    Cottonseed protein has the potential to be used as renewable and environmentally friendly adhesives in wood products industry. However, the industry application was limited by its low mechanical properties, low water resistance and viscosity. In this work, urea modified cottonseed protein adhesive w...

  14. Chemical and Biological Tools for the Preparation of Modified Histone Proteins

    PubMed Central

    Howard, Cecil J.; Yu, Ruixuan R.; Gardner, Miranda L.; Shimko, John C.; Ottesen, Jennifer J.

    2016-01-01

    Eukaryotic chromatin is a complex and dynamic system in which the DNA double helix is organized and protected by interactions with histone proteins. This system is regulated through, a large network of dynamic post-translational modifications (PTMs) exists to ensure proper gene transcription, DNA repair, and other processes involving DNA. Homogenous protein samples with precisely characterized modification sites are necessary to better understand the functions of modified histone proteins. Here, we discuss sets of chemical and biological tools that have been developed for the preparation of modified histones, with a focus on the appropriate choice of tool for a given target. We start with genetic approaches for the creation of modified histones, including the incorporation of genetic mimics of histone modifications, chemical installation of modification analogs, and the use of the expanded genetic code to incorporate modified amino acids. Additionally, we will cover the chemical ligation techniques that have been invaluable in the generation of complex modified histones that are indistinguishable from the natural counterparts. Finally, we will end with a prospectus on future directions of synthetic chromatin in living systems. PMID:25863817

  15. Using archived ITS data to measure the operational benefits of a system-wide adaptive ramp metering system : appendix online\\0x20101 : I\\0x2010205 NB time\\0x2010space speed contour plots with meter activations.

    DOT National Transportation Integrated Search

    2008-12-01

    Programmable logic controllers (PLCs) were installed at several key ramps with the assistance of the City of Portland and used to capture additional data about ramp operations that are not otherwise logged. The data include the activation and deactiv...

  16. Disruption avoidance and fast ramp-down techniques for the DIII-D experimental scenarios

    NASA Astrophysics Data System (ADS)

    Barr, Jayson; Eidietis, N. W.; Humphreys, D. A.; Sammuli, B.; Luce, T.

    2017-10-01

    Plasma current ramp-down in ITER will continue in H-mode from 15 MA to 10 MA, and will keep a diverted shape until termination. This is in contrast to the limited ramp-down scenarios typically used in DIII-D operations. Additionally, fast emergency ramp-down scenarios for ITER and future reactors are a priority for disruption avoidance. New experiments in DIII-D use the ramp-down phase of a variety of experiments including in the ITER baseline scenario to survey and identify optimized ramp-down scenarios for both scheduled terminations and terminations triggered by off-normal event detection. Systematic scans in current ramp-rate (1-5 MA/s), neutral beam power (including βN feedback) and ramp-down shaping (limited versus continued diverted) have identified fast ramp-down scenarios for Lower Single Null (LSN) and Double Null (DN) plasmas. Scenario-specific methods and their rates of successful termination will be presented and compared relative to a historical data-set of ramp-down programming in the limiter configuration. Locked modes are found to be the most significant challenge to disruption avoidance in diverted ramp-downs. Results for LSN diverted discharges that begin the rampdown with large locked-modes will also be presented. If available, results of similar experiments on EAST will be presented. Work supported by US DOE under DE-FC02-04ER54698 and DE-SC0010685.

  17. Expression of domains for protein-protein interaction of nucleotide excision repair proteins modifies cancer cell sensitivity to platinum derivatives and genomic stability.

    PubMed

    Jordheim, Lars Petter; Cros-Perrial, Emeline; Matera, Eva-Laure; Bouledrak, Karima; Dumontet, Charles

    2014-10-01

    Nucleotide excision repair (NER) is involved in the repair of DNA damage caused by platinum derivatives and has been shown to decrease the cytotoxic activity of these drugs. Because protein-protein interactions are essential for NER activity, we transfected human cancer cell lines (A549 and HCT116) with plasmids coding the amino acid sequences corresponding to the interacting domains between excision repair cross-complementation group 1 (ERCC1) and xeroderma pigmentosum, complementation group A (XPA), as well as ERCC1 and xeroderma pigmentosum, complementation group F (XPF), all NER proteins. Using the 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and annexin V staining, we showed that transfected A549 cells were sensitized 1.2-2.2-fold to carboplatin and that transfected HCT116 cells were sensitized 1.4-5.4-fold to oxaliplatin in vitro. In addition, transfected cells exhibited modified in vivo sensitivity to the same drugs. Finally, in particular cell models of the interaction between ERCC1 and XPF, DNA repair was decreased, as evidenced by increased phosphorylation of the histone 2AX after exposure to mitomycin C, and genomic instability was increased, as determined by comparative genomic hybridization studies. The results indicate that the interacting peptides act as dominant negatives and decrease NER activity through inhibition of protein-protein interactions. © 2014 Wiley Publishing Asia Pty Ltd.

  18. Programmable Multiple-Ramped-Voltage Power Supply

    NASA Technical Reports Server (NTRS)

    Ajello, Joseph M.; Howell, S. K.

    1993-01-01

    Ramp waveforms range up to 2,000 V. Laboratory high-voltage power-supply system puts out variety of stable voltages programmed to remain fixed with respect to ground or float with respect to ramp waveform. Measures voltages it produces with high resolution; automatically calibrates, zeroes, and configures itself; and produces variety of input/output signals for use with other instruments. Developed for use with ultraviolet spectrometer. Also applicable to control of electron guns in general and to operation of such diverse equipment used in measuring scattering cross sections of subatomic particles and in industrial electron-beam welders.

  19. PDR with a Foot-Mounted IMU and Ramp Detection

    PubMed Central

    Jiménez, Antonio R.; Seco, Fernando; Zampella, Francisco; Prieto, José C.; Guevara, Jorge

    2011-01-01

    The localization of persons in indoor environments is nowadays an open problem. There are partial solutions based on the deployment of a network of sensors (Local Positioning Systems or LPS). Other solutions only require the installation of an inertial sensor on the person’s body (Pedestrian Dead-Reckoning or PDR). PDR solutions integrate the signals coming from an Inertial Measurement Unit (IMU), which usually contains 3 accelerometers and 3 gyroscopes. The main problem of PDR is the accumulation of positioning errors due to the drift caused by the noise in the sensors. This paper presents a PDR solution that incorporates a drift correction method based on detecting the access ramps usually found in buildings. The ramp correction method is implemented over a PDR framework that uses an Inertial Navigation algorithm (INS) and an IMU attached to the person’s foot. Unlike other approaches that use external sensors to correct the drift error, we only use one IMU on the foot. To detect a ramp, the slope of the terrain on which the user is walking, and the change in height sensed when moving forward, are estimated from the IMU. After detection, the ramp is checked for association with one of the existing in a database. For each associated ramp, a position correction is fed into the Kalman Filter in order to refine the INS-PDR solution. Drift-free localization is achieved with positioning errors below 2 meters for 1,000-meter-long routes in a building with a few ramps. PMID:22163701

  20. Two-Dimensional Supersonic Nozzle Thrust Vectoring Using Staggered Ramps

    NASA Astrophysics Data System (ADS)

    Montes, Carlos Fernando

    A novel mechanism for vectoring the thrust of a supersonic, air-breathing engine was analyzed numerically using ANSYS Fluent. The mechanism uses two asymmetrically staggered ramps; one placed at the throat, the other positioned at the exit lip of the nozzle. The nozzle was designed using published flow data, isentropic relationships, and piecewise quartic splines. The design was verified numerically and was in fair agreement with the analytical data. Using the steady-state pressure-based solver, along with the realizable kappa - epsilon turbulence model, a total of eighteen simulations were conducted: three ramp lengths at three angles, using two sets of inlet boundary conditions (non-afterburning and afterburning). The vectoring simulations showed that the afterburning flow yields a lower flow deflection distribution, shown by the calculated average deflection angle and area-weighted integrals of the distributions. The data implies that an aircraft can achieve an average thrust vectoring angle of approximately 30° in a given direction with the longest ramp length and largest ramp angle configuration. With increasing ramp angle, the static pressure across the nozzle inlet increased, causing concern for potential negative effects on the engine's turbine. The mechanism, for which a provisional patent application has been filed, will require further work to investigate the maximum possible thrust vectoring angle, including experiments.

  1. RNA-modifying proteins as anticancer drug targets.

    PubMed

    Boriack-Sjodin, P Ann; Ribich, Scott; Copeland, Robert A

    2018-06-01

    All major biological macromolecules (DNA, RNA, proteins and lipids) undergo enzyme-catalysed covalent modifications that impact their structure, function and stability. A variety of covalent modifications of RNA have been identified and demonstrated to affect RNA stability and translation to proteins; these mechanisms of translational control have been termed epitranscriptomics. Emerging data suggest that some epitranscriptomic mechanisms are altered in human cancers as well as other human diseases. In this Review, we examine the current understanding of RNA modifications with a focus on mRNA methylation, highlight their possible roles in specific cancer indications and discuss the emerging potential of RNA-modifying proteins as therapeutic targets.

  2. Evolution of plasma wakes in density up- and down-ramps

    NASA Astrophysics Data System (ADS)

    Zhang, C. J.; Joshi, C.; Xu, X. L.; Mori, W. B.; Li, F.; Wan, Y.; Hua, J. F.; Pai, C. H.; Wang, J.; Lu, W.

    2018-02-01

    The time evolution of plasma wakes in density up- and down-ramps is examined through theory and particle-in-cell simulations. Motivated by observation of the reversal of a linear plasma wake in a plasma density upramp in a recent experiment (Zhang et al 2017 Phys. Rev. Lett. 119 064801) we have examined the behaviour of wakes in plasma ramps that always accompany any plasma source used for plasma-based acceleration. In the up-ramp case it is found that, after the passage of the drive pulse, the wavnumber/wavelength of the wake starts to decrease/increase with time until it eventually tends to zero/infinity, then the wake reverses its propagation direction and the wavenunber/wavelength of the wake begins to increase/shrink. The evolutions of the wavenumber and the phase velocity of the wake as functions of time are shown to be significantly different in the up-ramp and the down-ramp cases. In the latter case the wavenumber of the wake at a particular position in the ramp increases until the wake is eventually damped. It is also shown that the waveform of the wake at a particular time after being excited can be precisely controlled by tuning the initial plasma density profile, which may enable a new type of plasma-based ultrafast optics.

  3. Alteration and modulation of protein activity by varying post-translational modification

    DOEpatents

    Thompson, David N; Reed, David W; Thompson, Vicki S; Lacey, Jeffrey A; Apel, William A

    2015-03-03

    Embodiments of the invention include methods of altering the enzymatic activity or solubility of an extremophilic enzyme or post-translationally modifying a protein of interest via using isolated or partially purified glycosyltransferases and/or post-translational modification proteins, extracts of cells comprising glycosyltransferases and/or post-translational modification proteins, and/or in cells comprising one or more glycosyltransferases and/or post-translational modification proteins.

  4. Alteration and modulation of protein activity by varying post-translational modification

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

    Thompson, David N.; Reed, David W.; Thompson, Vicki S.

    Embodiments of the invention include methods of altering the enzymatic activity or solubility of an extremophilic enzyme or post-translationally modifying a protein of interest via using isolated or partially purified glycosyltransferases and/or post-translational modification proteins, extracts of cells comprising glycosyltransferases and/or post-translational modification proteins, and/or in cells comprising one or more glycosyltransferases and/or post-translational modification proteins.

  5. Brown pigment formation in heated sugar-protein mixed suspensions containing unmodified and peptically modified whey protein concentrates.

    PubMed

    Rongsirikul, Narumol; Hongsprabhas, Parichat

    2016-01-01

    Commercial whey protein concentrate (WPC) was modified by heating the acidified protein suspensions (pH 2.0) at 80 °C for 30 min and treating with pepsin at 37 °C for 60 min. Prior to spray-drying, such modification did not change the molecular weights (MWs) of whey proteins determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). After spray-drying the modified whey protein concentrate with trehalose excipient (MWPC-TH), it was found that the α-lactalbumin (α-La) was the major protein that was further hydrolyzed the most. The reconstituted MWPC-TH contained β-lactoglobulin (β-Lg) as the major protein and small molecular weight (MW) peptides of less than 6.5 kDa. The reconstituted MWPC-TH had higher NH2 group, Trolox equivalent antioxidant capacity (TEAC), lower exposed aromatic ring and thiol (SH) contents than did the commercial WPC. Kinetic studies revealed that the addition of MWPC-TH in fructose-glycine solution was able to reduce brown pigment formation in the mixtures heated at 80 to 95 °C by increasing the activation energy (Ea) of brown pigment formation due to the retardation of fluoresced advanced glycation end product (AGEs) formation. The addition of MWPC to reducing sugar-glycine/commercial WPC was also able to lower brown pigment formation in the sterilized (121 °C, 15 min) mixed suspensions containing 0.1 M reducing sugar and 0.5-1.0 % glycine and/or commercial (P < 0.05). It was demonstrated that the modification investigated in this study selectively hydrolyzed α-La and retained β-Lg for the production of antibrowning whey protein concentrate.

  6. Flow control of micro-ramps on supersonic forward-facing step flow

    NASA Astrophysics Data System (ADS)

    Qing-Hu, Zhang; Tao, Zhu; Shihe, Yi; Anping, Wu

    2016-05-01

    The effects of the micro-ramps on supersonic turbulent flow over a forward-facing step (FFS) was experimentally investigated in a supersonic low-noise wind tunnel at Mach number 3 using nano-tracer planar laser scattering (NPLS) and particle image velocimetry (PIV) techniques. High spatiotemporal resolution images and velocity fields of supersonic flow over the testing model were captured. The fine structures and their spatial evolutionary characteristics without and with the micro-ramps were revealed and compared. The large-scale structures generated by the micro-ramps can survive the downstream FFS flowfield. The micro-ramps control on the flow separation and the separation shock unsteadiness was investigated by PIV results. With the micro-ramps, the reduction in the range of the reversal flow zone in streamwise direction is 50% and the turbulence intensity is also reduced. Moreover, the reduction in the average separated region and in separation shock unsteadiness are 47% and 26%, respectively. The results indicate that the micro-ramps are effective in reducing the flow separation and the separation shock unsteadiness. Project supported by the National Natural Science Foundation of China (Grant Nos. 11172326 and 11502280).

  7. Developing an area-wide system for coordinated ramp meter control.

    DOT National Transportation Integrated Search

    2008-12-01

    Ramp metering has been broadly accepted and deployed as an effective countermeasure : against both recurrent and non-recurrent congestion on freeways. However, many current ramp : metering algorithms tend to improve only freeway travels using local d...

  8. Calcitonin and Amylin Receptor Peptide Interaction Mechanisms

    PubMed Central

    Lee, Sang-Min; Hay, Debbie L.; Pioszak, Augen A.

    2016-01-01

    Receptor activity-modifying proteins (RAMP1–3) determine the selectivity of the class B G protein-coupled calcitonin receptor (CTR) and the CTR-like receptor (CLR) for calcitonin (CT), amylin (Amy), calcitonin gene-related peptide (CGRP), and adrenomedullin (AM) peptides. RAMP1/2 alter CLR selectivity for CGRP/AM in part by RAMP1 Trp-84 or RAMP2 Glu-101 contacting the distinct CGRP/AM C-terminal residues. It is unclear whether RAMPs use a similar mechanism to modulate CTR affinity for CT and Amy, analogs of which are therapeutics for bone disorders and diabetes, respectively. Here, we reproduced the peptide selectivity of intact CTR, AMY1 (CTR·RAMP1), and AMY2 (CTR·RAMP2) receptors using purified CTR extracellular domain (ECD) and tethered RAMP1- and RAMP2-CTR ECD fusion proteins and antagonist peptides. All three proteins bound salmon calcitonin (sCT). Tethering RAMPs to CTR enhanced binding of rAmy, CGRP, and the AMY antagonist AC413. Peptide alanine-scanning mutagenesis and modeling of receptor-bound sCT and AC413 supported a shared non-helical CGRP-like conformation for their TN(T/V)G motif prior to the C terminus. After this motif, the peptides diverged; the sCT C-terminal Pro was crucial for receptor binding, whereas the AC413/rAmy C-terminal Tyr had little or no influence on binding. Accordingly, mutant RAMP1 W84A- and RAMP2 E101A-CTR ECD retained AC413/rAmy binding. ECD binding and cell-based signaling assays with antagonist sCT/AC413/rAmy variants with C-terminal residue swaps indicated that the C-terminal sCT/rAmy residue identity affects affinity more than selectivity. rAmy(8–37) Y37P exhibited enhanced antagonism of AMY1 while retaining selectivity. These results reveal unexpected differences in how RAMPs determine CTR and CLR peptide selectivity and support the hypothesis that RAMPs allosterically modulate CTR peptide affinity. PMID:26895962

  9. Modelling decremental ramps using 2- and 3-parameter "critical power" models.

    PubMed

    Morton, R Hugh; Billat, Veronique

    2013-01-01

    The "Critical Power" (CP) model of human bioenergetics provides a valuable way to identify both limits of tolerance to exercise and mechanisms that underpin that tolerance. It applies principally to cycling-based exercise, but with suitable adjustments for analogous units it can be applied to other exercise modalities; in particular to incremental ramp exercise. It has not yet been applied to decremental ramps which put heavy early demand on the anaerobic energy supply system. This paper details cycling-based bioenergetics of decremental ramps using 2- and 3-parameter CP models. It derives equations that, for an individual of known CP model parameters, define those combinations of starting intensity and decremental gradient which will or will not lead to exhaustion before ramping to zero; and equations that predict time to exhaustion on those decremental ramps that will. These are further detailed with suitably chosen numerical and graphical illustrations. These equations can be used for parameter estimation from collected data, or to make predictions when parameters are known.

  10. Risk assessment in ramps for heavy vehicles--A French study.

    PubMed

    Cerezo, Veronique; Conche, Florence

    2016-06-01

    This paper presents the results of a study dealing with the risk for heavy vehicles in ramps. Two approaches are used. On one hand, statistics are applied on several accidents databases to detect if ramps are more risky for heavy vehicles and to define a critical value for longitudinal slope. χ(2) test confirmed the risk in ramps and statistical analysis proved that a longitudinal slope superior to 3.2% represents a higher risk for heavy vehicles. On another hand, numerical simulations allow defining the speed profile in ramps for two types of heavy vehicles (tractor semi-trailer and 2-axles rigid body) and different loads. The simulations showed that heavy vehicles must drive more than 1000 m on ramps to reach their minimum speed. Moreover, when the slope is superior to 3.2%, tractor semi-trailer presents a strong decrease of their speed until 50 km/h. This situation represents a high risk of collision with other road users which drive at 80-90 km/h. Thus, both methods led to the determination of a risky configuration for heavy vehicles: ramps with a length superior to 1000 m and a slope superior to 3.2%. An application of this research work concerns design methods and guidelines. Indeed, this study provides threshold values than can be used by engineers to make mandatory specific planning like a lane for slow vehicles. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Anatomy of a cyclically packaged Mesoproterozoic carbonate ramp in northern Canada

    NASA Astrophysics Data System (ADS)

    Sherman, A. G.; Narbonne, G. M.; James, N. P.

    2001-03-01

    Carbonates in the upper member of the Mesoproterozoic Victor Bay Formation are dominated by lime mud and packaged in cycles of 20-50 m. These thicknesses exceed those of classic shallowing-upward cycles by almost a factor of 10. Stratigraphic and sedimentological evidence suggests high-amplitude, high-frequency glacio-eustatic cyclicity, and thus a cool global climate ca. 1.2 Ga. The Victor Bay ramp is one of several late Proterozoic carbonate platforms where the proportions of lime mud, carbonate grains, and microbialites are more typical of younger Phanerozoic successions which followed the global waning of stromatolites. Facies distribution in the study area is compatible with deposition on a low-energy, microtidal, distally steepened ramp. Outer-ramp facies are hemipelagic lime mudstone, shale, carbonaceous rhythmite, and debrites. Mid-ramp facies are molar-tooth limestone tempestite with microspar-intraclast lags. In a marine environment where stromatolitic and oolitic facies were otherwise rare, large stromatolitic reefs developed at the mid-ramp, coeval with inner-ramp facies of microspar grainstone, intertidal dolomitic microbial laminite, and supratidal evaporitic red shale. Deep-subtidal, outer-ramp cycles occur in the southwestern part of the study area. Black dolomitic shale at the base is overlain by ribbon, nodular, and carbonaceous carbonate facies, all of which exhibit signs of synsedimentary disruption. Cycles in the northeast are shallow-subtidal and peritidal in character. Shallow-subtidal cycles consist of basal deep-water facies, and an upper layer of subtidal molar-tooth limestone tempestite interbedded with microspar calcarenite facies. Peritidal cycles are identical to shallow-subtidal cycles except that they contain a cap of dolomitic tidal-flat microbial laminite, and rarely of red shale sabkha facies or of sandy polymictic conglomerate. A transect along the wall of a valley extending 8.5 km perpendicular to depositional strike reveals

  12. 16. Built c. 1936, this ramp from the first to ...

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

    16. Built c. 1936, this ramp from the first to the second floor along the northwestern side of Pier G (shown at the first floor) was called 'ramp C.' - Lehigh Valley Railroad, Pier G, Jersey City, Hudson County, NJ

  13. Combined replacement effects of human modified β-hexosaminidase B and GM2 activator protein on GM2 gangliosidoses fibroblasts.

    PubMed

    Kitakaze, Keisuke; Tasaki, Chikako; Tajima, Youichi; Hirokawa, Takatsugu; Tsuji, Daisuke; Sakuraba, Hitoshi; Itoh, Kohji

    2016-09-01

    GM2 gangliosidoses are autosomal recessive lysosomal storage diseases (LSDs) caused by mutations in the HEXA , HEXB and GM2A genes, which encode the human lysosomal β-hexosaminidase (Hex) α- and β-subunits, and GM2 activator protein (GM2A), respectively. These diseases are associated with excessive accumulation of GM2 ganglioside (GM2) in the brains of patients with neurological symptoms. Here we established a CHO cell line overexpressing human GM2A, and purified GM2A from the conditioned medium, which was taken up by fibroblasts derived from a patient with GM2A deficiency, and had the therapeutic effects of reducing the GM2 accumulated in fibroblasts when added to the culture medium. We also demonstrated for the first time that recombinant GM2A could enhance the replacement effect of human modified HexB (modB) with GM2-degrading activity, which is composed of homodimeric altered β-subunits containing a partial amino acid sequence of the α-subunit, including the GSEP loop necessary for binding to GM2A, on reduction of the GM2 accumulated in fibroblasts derived from a patient with Tay-Sachs disease, a HexA (αβ heterodimer) deficiency, caused by HEXA mutations. We predicted the same manner of binding of GM2A to the GSEP loop located in the modified HexB β-subunit to that in the native HexA α-subunit on the basis of the x-ray crystal structures. These findings suggest the effectiveness of combinational replacement therapy involving the human modified HexB and GM2A for GM2 gangliosidoses.

  14. Explaining Ramps with Models

    ERIC Educational Resources Information Center

    Campbell, Todd; Neilson, Drew

    2016-01-01

    In this article Campbell and Neilson discuss several design strategies developed or adopted that were found particularly helpful when sequencing a unit that focused on learning about motion and acceleration. Students were expected to predict, observe, and explain why a ball traveled down one ramp faster than the other. Before engaging students,…

  15. On Asymptotically Good Ramp Secret Sharing Schemes

    NASA Astrophysics Data System (ADS)

    Geil, Olav; Martin, Stefano; Martínez-Peñas, Umberto; Matsumoto, Ryutaroh; Ruano, Diego

    Asymptotically good sequences of linear ramp secret sharing schemes have been intensively studied by Cramer et al. in terms of sequences of pairs of nested algebraic geometric codes. In those works the focus is on full privacy and full reconstruction. In this paper we analyze additional parameters describing the asymptotic behavior of partial information leakage and possibly also partial reconstruction giving a more complete picture of the access structure for sequences of linear ramp secret sharing schemes. Our study involves a detailed treatment of the (relative) generalized Hamming weights of the considered codes.

  16. Cortical activity associated with the perception of temporal asymmetry in ramped and damped noises.

    PubMed

    Rupp, André; Spachmann, André; Dettlaff, Anna; Patterson, Roy D

    2013-01-01

    Human listeners are very sensitive to the asymmetry of time-reversed pairs of ramped and damped sounds. When the carrier is noise, the hiss -component of the perception is stronger in ramped sounds and the drumming component is stronger in damped sounds (Akeroyd and Patterson 1995). In the current study, a paired comparison technique was used to establish the relative "hissiness" of these noises, and the ratings were correlated with (a) components of the auditory evoked field (AEF) produced by these noises and (b) the magnitude of a hissiness feature derived from a model of the internal auditory images produced by these noises (Irino and Patterson 1998). An earlier AEF report indicated that the peak magnitude of the transient N100m response mirrors the perceived salience of the tonal perception (Rupp et al. 2005). The AEFs of 14 subjects were recorded in response to damped/ramped noises with half-lives between 1 and 64 ms and repetition rates between 12.5 and 100 ms. Spatio-temporal source analysis was used to fit the P50m, the P200m, and the sustained field (SF). These noise stimuli did not produce a reliable N100m. The hissiness feature from the auditory model was extracted from a time-averaged sequence of summary auditory images as in Patterson and Irino (1998). The results show that the perceptual measure of hissiness is highly correlated with the hissiness feature from the summary auditory image, and both are highly correlated with the magnitude of the transient P200m. There is a significant but weaker correlation with the SF and a nonsignificant correlation with the P50m. The results suggest that regularity in the carrier effects branching at an early stage of auditory processing with tonal and noisy sounds following separate spatio-temporal routes through the system.

  17. Recombinant modified vaccinia virus Ankara generating excess early double-stranded RNA transiently activates protein kinase R and triggers enhanced innate immune responses.

    PubMed

    Wolferstätter, Michael; Schweneker, Marc; Späth, Michaela; Lukassen, Susanne; Klingenberg, Marieken; Brinkmann, Kay; Wielert, Ursula; Lauterbach, Henning; Hochrein, Hubertus; Chaplin, Paul; Suter, Mark; Hausmann, Jürgen

    2014-12-01

    Double-stranded RNA (dsRNA) is an important molecular pattern associated with viral infection and is detected by various extra- and intracellular recognition molecules. Poxviruses have evolved to avoid producing dsRNA early in infection but generate significant amounts of dsRNA late in infection due to convergent transcription of late genes. Protein kinase R (PKR) is activated by dsRNA and triggers major cellular defenses against viral infection, including protein synthesis shutdown, apoptosis, and type I interferon (IFN-I) production. The poxviral E3 protein binds and sequesters viral dsRNA and is a major antagonist of the PKR pathway. We found that the highly replication-restricted modified vaccinia virus Ankara (MVA) engineered to produce excess amounts of dsRNA early in infection showed enhanced induction of IFN-β in murine and human cells in the presence of an intact E3L gene. IFN-β induction required a minimum overlap length of 300 bp between early complementary transcripts and was strongly PKR dependent. Excess early dsRNA produced by MVA activated PKR early but transiently in murine cells and induced enhanced systemic levels of IFN-α, IFN-γ, and other cytokines and chemokines in mice in a largely PKR-dependent manner. Replication-competent chorioallantois vaccinia virus Ankara (CVA) generating excess early dsRNA also enhanced IFN-I production and was apathogenic in mice even at very high doses but showed no in vitro host range defect. Thus, genetically adjuvanting MVA and CVA to generate excess early dsRNA is an effective method to enhance innate immune stimulation by orthopoxvirus vectors and to attenuate replicating vaccinia virus in vivo. Efficient cellular sensing of pathogen-specific components, including double-stranded RNA (dsRNA), is an important prerequisite of an effective antiviral immune response. The prototype poxvirus vaccinia virus (VACV) and its derivative modified vaccinia virus Ankara (MVA) produce dsRNA as a by-product of viral

  18. Experimental study of the active control applied to the flow past a backward facing ramp

    NASA Astrophysics Data System (ADS)

    Hlevca, Dan; Gilliéron, Patrick; Grasso, Francesco

    2018-03-01

    An experimental study of open loop active flow control on a backward facing ramp is presented. The ramp has finite span and a slant angle of 25°. Wind tunnel experiments were performed both for the uncontrolled and the controlled cases where time periodic forcing by pulsed jets is considered. The control system exploits an electro-magnetic valve system to generate pulsed jets with an operating frequency and duty cycle ranging, respectively, between 50 and 250 Hz and between 25 and 60%. A parametric study was carried out for three different freestream velocities and varying the frequency of the pulsed jets and the duty cycle. The control strategy relies on the injection of periodic perturbations before separation at the edge of the slant, considering various combinations of frequencies and duty cycles while keeping constant the blowing time for every Reynolds number, so as to excite the flow with the same jet structure over different actuation cycle extents. The receptivity of the flow to periodic forcing was assessed by characterizing mean and unsteady flow properties, turbulence statistics and flow topology. The study focused on the impact of control on reattachement and showed that the flow locks with excitation frequencies typical of initial Kelvin-Helmholtz instabilities. However, the flow was found to respond to any injected unsteady perturbation locking to the forcing frequencies and the extent of the region where locking occurs was found to be of the order of a few slant heights. A relaxation process was observed and the flow was found to relax past the slant trailing edge toward frequencies close to the natural ones.

  19. Regulation of protein activity with small-molecule-controlled inteins

    PubMed Central

    Skretas, Georgios; Wood, David W.

    2005-01-01

    Inteins are the protein analogs of self-splicing RNA introns, as they post-translationally excise themselves from a variety of protein hosts. Intein insertion abolishes, in general, the activity of its host protein, which is subsequently restored upon intein excision. These protein elements therefore have the potential to be used as general molecular “switches” for the control of arbitrary target proteins. Based on rational design, an intein-based protein switch has been constructed whose splicing activity is conditionally triggered in vivo by the presence of thyroid hormone or synthetic analogs. This modified intein was used in Escherichia coli to demonstrate that a number of different proteins can be inactivated by intein insertion and then reactivated by the addition of thyroid hormone via ligand-induced splicing. This conditional activation was also found to occur in a dose-dependent manner. Rational protein engineering was then combined with genetic selection to evolve an additional intein whose activity is controlled by the presence of synthetic estrogen ligands. The ability to regulate protein function post-translationally through the use of ligand-controlled intein splicing will most likely find applications in metabolic engineering, drug discovery and delivery, biosensing, molecular computation, as well as many additional areas of biotechnology. PMID:15632292

  20. Systematic Errors in Peptide and Protein Identification and Quantification by Modified Peptides*

    PubMed Central

    Bogdanow, Boris; Zauber, Henrik; Selbach, Matthias

    2016-01-01

    The principle of shotgun proteomics is to use peptide mass spectra in order to identify corresponding sequences in a protein database. The quality of peptide and protein identification and quantification critically depends on the sensitivity and specificity of this assignment process. Many peptides in proteomic samples carry biochemical modifications, and a large fraction of unassigned spectra arise from modified peptides. Spectra derived from modified peptides can erroneously be assigned to wrong amino acid sequences. However, the impact of this problem on proteomic data has not yet been investigated systematically. Here we use combinations of different database searches to show that modified peptides can be responsible for 20–50% of false positive identifications in deep proteomic data sets. These false positive hits are particularly problematic as they have significantly higher scores and higher intensities than other false positive matches. Furthermore, these wrong peptide assignments lead to hundreds of false protein identifications and systematic biases in protein quantification. We devise a “cleaned search” strategy to address this problem and show that this considerably improves the sensitivity and specificity of proteomic data. In summary, we show that modified peptides cause systematic errors in peptide and protein identification and quantification and should therefore be considered to further improve the quality of proteomic data annotation. PMID:27215553

  1. Dynamic Behaviors of Materials under Ramp Wave Loading on Compact Pulsed Power Generators

    NASA Astrophysics Data System (ADS)

    Zhao, Jianheng; Luo, Binqiang; Wang, Guiji; Chong, Tao; Tan, Fuli; Liu, Cangli; Sun, Chengwei

    The technique using intense current to produce magnetic pressure provides a unique way to compress matter near isentrope to high density without obvious temperature increment, which is characterized as ramp wave loading, and firstly developed by Sandia in 1998. Firstly recent advances on compact pulsed power generators developed in our laboratory, such as CQ-4, CQ-3-MMAF and CQ-7 devices, are simply introduced here, which devoted to ramp wave loading from 50GPa to 200 GPa, and to ultrahigh-velocity flyer launching up to 30 km/s. And then, we show our progress in data processing methods and experiments of isentropic compression conducted on these devices mentioned above. The suitability of Gruneisen EOS and Vinet EOS are validated by isentropic experiments of tantalum, and the parameters of SCG constitutive equation of aluminum and copper are modified to give better prediction under isentropic compression. Phase transition of bismuth and tin are investigated under different initial temperatures, parameters of Helmholtz free energy and characteristic relaxation time in kinetic phase transition equation are calibrated. Supported by NNSF of China under Contract No.11327803 and 11176002

  2. Possibilities of fish passage through the block ramp: Model-based estimation of permeability.

    PubMed

    Plesiński, Karol; Bylak, Aneta; Radecki-Pawlik, Artur; Mikołajczyk, Tomasz; Kukuła, Krzysztof

    2018-08-01

    Block ramps offer an opportunity to combine hydrotechnical structures with fish passages. The primary study objective was to evaluate the effectiveness of a block ramp for upstream fish movement in a mountain stream. Geodetic measurements of the bottom surface and water level were taken for three cross-sections. The description of the geometric and hydrodynamic parameters of the block ramp was supplemented with information on the width and length of crevices between boulders. Measurements of the geometric and hydrodynamic parameters of the block ramp were performed at 76 measurement sites, at three different types of discharge. Ichthyological data were collected in the analyzed stream. Measurements covered among others total length, width, and height of caught fish. Salmonid, cottid, balitorid, and cyprinid fish were studied. The determination of the main effects of the geometric and hydrodynamic parameters of the block ramp on the possibilities of use by target fish species employed generalized linear models (GLMs). The study shows that the block ramp cannot provide longitudinal connectivity and migration of fish occurring in the mountain stream. According to estimates, the block ramp did not meet the permeability expectations. The reason for low usefulness of the ramp for fish is particularly excessively strong water current. The stream concentration constituted an unsurmountable velocity barrier for fish moving upstream for each of the analyzed discharges. The developed model suggests that some crevices in the side zones of the ramp could be parts of the migration corridor, but only for small and medium-sized fish. At medium and high water stages, movement of fish in crevices was difficult due to fast water current, and at low and very low discharges, some crevices lost their permeability, and could become ecological traps for fish. The necessity of estimation of ramp permeability during pre-construction phase was emphasized. Copyright © 2018 Elsevier B.V. All

  3. A sustainable slashing industry using biodegradable sizes from modified soy protein to replace petro-based poly(vinyl alcohol).

    PubMed

    Zhao, Yi; Zhao, Yuzhu; Xu, Helan; Yang, Yiqi

    2015-02-17

    Biodegradable sizing agents from triethanolamine (TEA) modified soy protein could substitute poly(vinyl alcohol)(PVA) sizes for high-speed weaving of polyester and polyester/cotton yarns to substantially decrease environmental pollution and impel sustainability of textile industry. Nonbiodegradable PVA sizes are widely used and mainly contribute to high chemical oxygen demand (COD) in textile effluents. It has not been possible to effectively degrade, reuse or replace PVA sizes so far. Soy protein with good biodegradability showed potential as warp sizes in our previous studies. However, soy protein sizes lacked film flexibility and adhesion for required high-speed weaving. Additives with multiple hydroxyl groups, nonlinear molecule, and electric charge could physically modify secondary structure of soy protein and lead to about 23.6% and 43.3% improvement in size adhesion and ability of hair coverage comparing to unmodified soy protein. Industrial weaving results showed TEA-soy protein had relative weaving efficiency 3% and 10% higher than PVA and chemically modified starch sizes on polyester/cotton fabrics, and had relative weaving efficiency similar to PVA on polyester fabrics, although with 3- 6% lower add-on. In addition, TEA-soy sizes had a BOD5/COD ratio of 0.44, much higher than 0.03 for PVA, indicating that TEA-soy sizes were easily biodegradable in activated sludge.

  4. [Interaction of chaotropically modified immunoglobulins with protein and glicolipid antigens].

    PubMed

    Gordienko, A I; Khimich, N V

    2006-01-01

    The features of interaction of native and chaotropically modified immunoglobulins with proteins (ovalbumin) and glicolipids (lipopolysaccharides, LPS) enterobacteria Escherichia coli K235, Salmonella minnesota and Salmonella enteritidis have been investigated. It has been established, that after processing of native antibodies with 3.5 M KSCN their ability to contact to the specified antigenes repeatedly grows. Besides the intensity of interaction of modified immunoglobulins with the mentioned above antigenes was various, that is determined by the presence of structural distinctions between antigen determinants of proteins and glycolipid antigens, and also between O-polysaccharide chains of LPS in different species of enterobacteria.

  5. Assessing the Effectiveness of Ramp-Up During Sonar Operations Using Exposure Models.

    PubMed

    von Benda-Beckmann, Alexander M; Wensveen, Paul J; Kvadsheim, Petter H; Lam, Frans-Peter A; Miller, Patrick J O; Tyack, Peter L; Ainslie, Michael A

    2016-01-01

    Ramp-up procedures are used to mitigate the impact of sound on marine mammals. Sound exposure models combined with observations of marine mammals responding to sound can be used to assess the effectiveness of ramp-up procedures. We found that ramp-up procedures before full-level sonar operations can reduce the risk of hearing threshold shifts with marine mammals, but their effectiveness depends strongly on the responsiveness of the animals. In this paper, we investigated the effect of sonar parameters (source level, pulse-repetition time, ship speed) on sound exposure by using a simple analytical model and highlight the mechanisms that limit the effectiveness of ramp-up procedures.

  6. Facility No. S362, view across the ramp U.S. Naval ...

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

    Facility No. S362, view across the ramp - U.S. Naval Base, Pearl Harbor, Seaplane Ramps - World War II Type, Southwest and west shore of Ford Island, near Wasp Boulevard, Pearl City, Honolulu County, HI

  7. Ramp-edge structured tunneling devices using ferromagnet electrodes

    DOEpatents

    Kwon, Chuhee [Long Beach, CA; Jia, Quanxi [Los Alamos, NM

    2002-09-03

    The fabrication of ferromagnet-insulator-ferromagnet magnetic tunneling junction devices using a ramp-edge geometry based on, e.g., (La.sub.0.7 Sr.sub.0.3) MnO.sub.3, ferromagnetic electrodes and a SrTiO.sub.3 insulator is disclosed. The maximum junction magnetoresistance (JMR) as large as 23% was observed below 300 Oe at low temperatures (T<100 K). These ramp-edge junctions exhibited JMR of 6% at 200 K with a field less than 100 Oe.

  8. Identification and Modulation of the Key Amino Acid Residue Responsible for the pH Sensitivity of Neoculin, a Taste-Modifying Protein

    PubMed Central

    Nakajima, Ken-ichiro; Yokoyama, Kanako; Koizumi, Taichi; Koizumi, Ayako; Asakura, Tomiko; Terada, Tohru; Masuda, Katsuyoshi; Ito, Keisuke; Shimizu-Ibuka, Akiko; Misaka, Takumi; Abe, Keiko

    2011-01-01

    Neoculin occurring in the tropical fruit of Curculigo latifolia is currently the only protein that possesses both a sweet taste and a taste-modifying activity of converting sourness into sweetness. Structurally, this protein is a heterodimer consisting of a neoculin acidic subunit (NAS) and a neoculin basic subunit (NBS). Recently, we found that a neoculin variant in which all five histidine residues are replaced with alanine elicits intense sweetness at both neutral and acidic pH but has no taste-modifying activity. To identify the critical histidine residue(s) responsible for this activity, we produced a series of His-to-Ala neoculin variants and evaluated their sweetness levels using cell-based calcium imaging and a human sensory test. Our results suggest that NBS His11 functions as a primary pH sensor for neoculin to elicit taste modification. Neoculin variants with substitutions other than His-to-Ala were further analyzed to clarify the role of the NBS position 11 in the taste-modifying activity. We found that the aromatic character of the amino acid side chain is necessary to elicit the pH-dependent sweetness. Interestingly, since the His-to-Tyr variant is a novel taste-modifying protein with alternative pH sensitivity, the position 11 in NBS can be critical to modulate the pH-dependent activity of neoculin. These findings are important for understanding the pH-sensitive functional changes in proteinaceous ligands in general and the interaction of taste receptor–taste substance in particular. PMID:21559382

  9. Crescentic ramp turbine stage

    NASA Technical Reports Server (NTRS)

    Lee, Ching-Pang (Inventor); Tam, Anna (Inventor); Kirtley, Kevin Richard (Inventor); Lamson, Scott Henry (Inventor)

    2007-01-01

    A turbine stage includes a row of airfoils joined to corresponding platforms to define flow passages therebetween. Each airfoil includes opposite pressure and suction sides and extends in chord between opposite leading and trailing edges. Each platform includes a crescentic ramp increasing in height from the leading and trailing edges toward the midchord of the airfoil along the pressure side thereof.

  10. 2. Overview showing Medical Detachment Barracks on both Ramp No. ...

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

    2. Overview showing Medical Detachment Barracks on both Ramp No. 5 (left buildings) and Ramp No. 6 (right buildings). View is to west from roof of Corridor A. Note that a pedestrian sidewalk separates buildings instead of a street for automobiles. In left foreground is the north end of Building No. 9962-B; followed by the north B-sides of Buildings Nos. 9963, 9964, 9965, 9966, 9967 and 9968 on Ramp No. 5. Large white building in far distance is a barracks on the other side of Wilson Avenue. - Madigan Hospital, Medical Detachment Barracks, Bounded by Wilson & McKinley Avenues & Garfield & Lincoln Streets, Tacoma, Pierce County, WA

  11. Plasma-Assisted Control of Mach-2 Flowfield over Ramp Geometry

    NASA Astrophysics Data System (ADS)

    Watanabe, Yasumasa; Leonov, Sergey B.; Houpt, Alec; Hedlund, Brock E.; Elliott, Skye

    2017-10-01

    This study examined the effect of Reynolds number on plasma-assisted flow control ahead of a compression ramp geometry in Mach-2 supersonic flow. The experiments were conducted in the supersonic wind tunnel SBR-50 at the University of Notre Dame. Stagnation temperature and pressure were varied as T0=294-500K and P0=1-3bar to attain Reynolds number ranging from 3.4×105-2.2×106. Ramp pressure measurements, schlieren visualization, and high-speed camera imaging were used for the evaluation of plasma-assisted flow control effects. A linear dependency was found between the ramp pressure change per averaged plasma power and Reynolds number.

  12. Demonstration of Advanced C/SiC Cooled Ramp

    NASA Technical Reports Server (NTRS)

    Bouquet, Clement; Laithier, Frederic; Lawrence, Timothy; Eckel, Andrew; Munafo, Paul M. (Technical Monitor)

    2002-01-01

    Under a NASA contract, SPS is evaluating its C/SiC to metal brazing technique for the development of light, composite, actively cooled panels. The program first consisted of defining a system applicable to the X-33 nozzle ramp. SPS then performed evaluation tests for tube, composite, and braze material selection, and for the adaptation of braze process parameters to the parts geometry. SPS is presently manufacturing a 250x60 millimeter squared specimen, including 10 metallic tubes, which will be cycled in the NASA/GRC-CELL-22 test bed under engine representative conditions.

  13. Assessment of peak oxygen uptake during handcycling: Test-retest reliability and comparison of a ramp-incremented and perceptually-regulated exercise test.

    PubMed

    Hutchinson, Michael J; Paulson, Thomas A W; Eston, Roger; Goosey-Tolfrey, Victoria L

    2017-01-01

    To examine the reliability of a perceptually-regulated maximal exercise test (PRETmax) to measure peak oxygen uptake ([Formula: see text]) during handcycle exercise and to compare peak responses to those derived from a ramp-incremented protocol (RAMP). Twenty recreationally active individuals (14 male, 6 female) completed four trials across a 2-week period, using a randomised, counterbalanced design. Participants completed two RAMP protocols (20 W·min-1) in week 1, followed by two PRETmax in week 2, or vice versa. The PRETmax comprised five, 2-min stages clamped at Ratings of Perceived Exertion (RPE) 11, 13, 15, 17 and 20. Participants changed power output (PO) as often as required to maintain target RPE. Gas exchange variables (oxygen uptake, carbon dioxide production, minute ventilation), heart rate (HR) and PO were collected throughout. Differentiated RPE were collected at the end of each stage throughout trials. For relative [Formula: see text], coefficient of variation (CV) was equal to 4.1% and 4.8%, with ICC(3,1) of 0.92 and 0.85 for repeated measures from PRETmax and RAMP, respectively. Measurement error was 0.15 L·min-1 and 2.11 ml·kg-1·min-1 in PRETmax and 0.16 L·min-1 and 2.29 ml·kg-1·min-1 during RAMP for determining absolute and relative [Formula: see text], respectively. The difference in [Formula: see text] between PRETmax and RAMP was tending towards statistical significance (26.2 ± 5.1 versus 24.3 ± 4.0 ml·kg-1·min-1, P = 0.055). The 95% LoA were -1.9 ± 4.1 (-9.9 to 6.2) ml·kg-1·min-1. The PRETmax can be used as a reliable test to measure [Formula: see text] during handcycle exercise in recreationally active participants. Whilst PRETmax tended towards significantly greater [Formula: see text] values than RAMP, the difference is smaller than measurement error of determining [Formula: see text] from PRETmax and RAMP.

  14. Intein-modified enzymes, their production and industrial applications

    DOEpatents

    Apgar, James; Lessard, Philip; Raab, Michael R.; Shen, Binzhang; Lazar, Gabor; de la Vega, Humberto

    2016-10-11

    A method of predicting an intein insertion site in a protein that will lead to a switching phenotype is provided. The method includes identifying a plurality of C/T/S sites within the protein; selecting from the plurality of C/T/S/ sites those that are ranked 0.75 or higher by a support vector machine, within ten angstroms of the active site of the protein, and at or near a loop-.beta.-sheet junction or a loop-.alpha.-helix junction. A method of controlling protein activity and hosts including proteins with controlled activity are also provided. Also, intein modified proteins and plants containing intein modified proteins are provided.

  15. Integrated database and analysis system for the evaluation of freeway corridors for potential ramp signaling : [summary].

    DOT National Transportation Integrated Search

    2011-01-01

    Ramp signaling is the installation of traffic signals on freeway on-ramps. Studies have shown that in many locations, ramp signaling helped alleviate traffic congestion and improve safety. However, not all freeway locations are suitable for ramp sign...

  16. A Copula-Based Conditional Probabilistic Forecast Model for Wind Power Ramps

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

    Hodge, Brian S; Krishnan, Venkat K; Zhang, Jie

    Efficient management of wind ramping characteristics can significantly reduce wind integration costs for balancing authorities. By considering the stochastic dependence of wind power ramp (WPR) features, this paper develops a conditional probabilistic wind power ramp forecast (cp-WPRF) model based on Copula theory. The WPRs dataset is constructed by extracting ramps from a large dataset of historical wind power. Each WPR feature (e.g., rate, magnitude, duration, and start-time) is separately forecasted by considering the coupling effects among different ramp features. To accurately model the marginal distributions with a copula, a Gaussian mixture model (GMM) is adopted to characterize the WPR uncertaintymore » and features. The Canonical Maximum Likelihood (CML) method is used to estimate parameters of the multivariable copula. The optimal copula model is chosen based on the Bayesian information criterion (BIC) from each copula family. Finally, the best conditions based cp-WPRF model is determined by predictive interval (PI) based evaluation metrics. Numerical simulations on publicly available wind power data show that the developed copula-based cp-WPRF model can predict WPRs with a high level of reliability and sharpness.« less

  17. Orally active-targeted drug delivery systems for proteins and peptides.

    PubMed

    Li, Xiuying; Yu, Miaorong; Fan, Weiwei; Gan, Yong; Hovgaard, Lars; Yang, Mingshi

    2014-09-01

    In the past decade, extensive efforts have been devoted to designing 'active targeted' drug delivery systems (ATDDS) to improve oral absorption of proteins and peptides. Such ATDDS enhance cellular internalization and permeability of proteins and peptides via molecular recognition processes such as ligand-receptor or antigen-antibody interaction, and thus enhance drug absorption. This review focuses on recent advances with orally ATDDS, including ligand-protein conjugates, recombinant ligand-protein fusion proteins and ligand-modified carriers. In addition to traditional intestinal active transport systems of substrates and their corresponding receptors, transporters and carriers, new targets such as intercellular adhesion molecule-1 and β-integrin are also discussed. ATDDS can improve oral absorption of proteins and peptides. However, currently, no clinical studies on ATDDS for proteins and peptides are underway, perhaps due to the complexity and limited knowledge of transport mechanisms. Therefore, more research is warranted to optimize ATDDS efficiency.

  18. 14. VIEW OF THE MODERN CONCRETE RAMP THAT CONNECTED THE ...

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

    14. VIEW OF THE MODERN CONCRETE RAMP THAT CONNECTED THE UPPER AND LOWER MINE ROADS. TRUCKS USED THIS RAMP AND THE ROADS TO HAUL SLAG TO THE MINE DUMP. - Tower Hill No. 2 Mine, Approximately 0.47 mile Southwest of intersection of Stone Church Road & Township Route 561, Hibbs, Fayette County, PA

  19. Protein-Nanoparticle Interactions: Improving Immobilized Lytic Enzyme Activity and Surface Energy Effects

    NASA Astrophysics Data System (ADS)

    Downs, Emily Elizabeth

    Protein-nanostructure conjugates, particularly particles, are a subject of significant interest due to changes in their fundamental behavior compared to bulk surfaces. As the size scale of nano-structured materials and proteins are on the same order of magnitude, nanomaterial properties can heavily influence how proteins adsorb and conform to the surface. Previous work has demonstrated the ability of nanoscale surfaces to modulate protein activity, conformation, and retention by modifying the particle surface curvature, morphology, and surface charge. This work has improved our understanding of the protein material interactions, but a complete understanding is still lacking. The goal of this thesis is to investigate two missing areas of understanding using two distinct systems. The first system utilizes a particle with controlled surface energy to observe the impact of surface energy on protein-particle interactions, while the second system uses a modified Listeria-specific protein to determine how protein structure and flexibility affects protein adsorption and activity on particles. Spherical, amorphous, and uniformly doped Zn-silica particles with tailored surface energies were synthesized to understand the impact of surface energy on protein adsorption behavior. Particle surface energy increased with a decrease in particle size and greater dopant concentrations. Protein adsorption and structural loss increased with both particle size and particle surface energy. Higher surface energies promoted protein-particle association and increased protein unfolding. Particle curvature and protein steric hindrance effects limited adsorption and structural loss on smaller particles. Protein surface charge heterogeneity was also found to be linked to both protein adsorption and unfolding behavior on larger particles. Greater surface charge heterogeneity led to higher adsorption concentrations and multilayer formation. These multilayers transitioned from protein

  20. Aerial view looking northwest showing location of seaplane ramps 2,3, ...

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

    Aerial view looking northwest showing location of seaplane ramps 2,3, and 4. Ramps lead from buildings 1 and 2, bayside left center, into San Diego Bay. - Naval Air Station North Island, North Island, San Diego, San Diego County, CA

  1. Preparation of Gc protein-derived macrophage activating factor (GcMAF) and its structural characterization and biological activities.

    PubMed

    Mohamad, Saharuddin Bin; Nagasawa, Hideko; Uto, Yoshihiro; Hori, Hitoshi

    2002-01-01

    Gc protein has been reported to be a precursor of Gc protein-derived macrophage activation factor (GcMAF) in the inflammation-primed macrophage activation cascade. An inducible beta-galactosidase of B cells and neuraminidase of T cells convert Gc protein to GcMAF. Gc protein from human serum was purified using 25(OH)D3 affinity column chromatography and modified to GcMAF using immobilized glycosidases (beta-galactosidase and neuraminidase) The sugar moiety structure of GcMAF was characterized by lectin blotting by Helix pomatia agglutinin. The biological activities of GcMAF were evaluated by a superoxide generation assay and a phagocytosis assay. We successfully purified Gc protein from human serum. GcMAF was detected by lectin blotting and showed a high biological activity. Our results support the importance of the terminal N-acetylgalactosamine moiety in the GcMAF-mediated macrophage activation cascade, and the existence of constitutive GcMAF in human serum. These preliminary data are important for designing small molecular GcMAF mimics.

  2. Metabolic labeling enables selective photocrosslinking of O-GlcNAc-modified proteins to their binding partners

    PubMed Central

    Yu, Seok-Ho; Boyce, Michael; Wands, Amberlyn M.; Bond, Michelle R.; Bertozzi, Carolyn R.; Kohler, Jennifer J.

    2012-01-01

    O-linked β-N-acetylglucosamine (O-GlcNAc) is a reversible posttranslational modification found on hundreds of nuclear and cytoplasmic proteins in higher eukaryotes. Despite its ubiquity and essentiality in mammals, functional roles for the O-GlcNAc modification remain poorly defined. Here we develop a combined genetic and chemical approach that enables introduction of the diazirine photocrosslinker onto the O-GlcNAc modification in cells. We engineered mammalian cells to produce diazirine-modified O-GlcNAc by expressing a mutant form of UDP-GlcNAc pyrophosphorylase and subsequently culturing these cells with a cell-permeable, diazirine-modified form of GlcNAc-1-phosphate. Irradiation of cells with UV light activated the crosslinker, resulting in formation of covalent bonds between O-GlcNAc-modified proteins and neighboring molecules, which could be identified by mass spectrometry. We used this method to identify interaction partners for the O-GlcNAc-modified FG-repeat nucleoporins. We observed crosslinking between FG-repeat nucleoporins and nuclear transport factors, suggesting that O-GlcNAc residues are intimately associated with essential recognition events in nuclear transport. Further, we propose that the method reported here could find widespread use in investigating the functional consequences of O-GlcNAcylation. PMID:22411826

  3. Bio-active molecules modified surfaces enhanced mesenchymal stem cell adhesion and proliferation

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

    Mobasseri, Rezvan; Center for Nanofibers & Nanotechnology, Department of Mechanical Engineering, National University of Singapore, 117576; Tian, Lingling

    Surface modification of the substrate as a component of in vitro cell culture and tissue engineering, using bio-active molecules including extracellular matrix (ECM) proteins or peptides derived ECM proteins can modulate the surface properties and thereby induce the desired signaling pathways in cells. The aim of this study was to evaluate the behavior of human bone marrow mesenchymal stem cells (hBM-MSCs) on glass substrates modified with fibronectin (Fn), collagen (Coll), RGD peptides (RGD) and designed peptide (R-pept) as bio-active molecules. The glass coverslips were coated with fibronectin, collagen, RGD peptide and R-peptide. Bone marrow mesenchymal stem cells were cultured on differentmore » substrates and the adhesion behavior in early incubation times was investigated using scanning electron microscopy (SEM) and confocal microscopy. The MTT assay was performed to evaluate the effect of different bio-active molecules on MSCs proliferation rate during 24 and 72 h. Formation of filopodia and focal adhesion (FA) complexes, two steps of cell adhesion process, were observed in MSCs cultured on bio-active molecules modified coverslips, specifically in Fn coated and R-pept coated groups. SEM image showed well adhesion pattern for MSCs cultured on Fn and R-pept after 2 h incubation, while the shape of cells cultured on Coll and RGD substrates indicated that they might experience stress condition in early hours of culture. Investigation of adhesion behavior, as well as proliferation pattern, suggests R-peptide as a promising bio-active molecule to be used for surface modification of substrate in supporting and inducing cell adhesion and proliferation. - Highlights: • Bioactive molecules modified surface is a strategy to design biomimicry scaffold. • Bi-functional Tat-derived peptide (R-pept) enhanced MSCs adhesion and proliferation. • R-pept showed similar influences to fibronectin on FA formation and attachment.« less

  4. Shock formation and the ideal shape of ramp compression waves

    NASA Astrophysics Data System (ADS)

    Swift, Damian C.; Kraus, Richard G.; Loomis, Eric N.; Hicks, Damien G.; McNaney, James M.; Johnson, Randall P.

    2008-12-01

    We derive expressions for shock formation based on the local curvature of the flow characteristics during dynamic compression. Given a specific ramp adiabat, calculated for instance from the equation of state for a substance, the ideal nonlinear shape for an applied ramp loading history can be determined. We discuss the region affected by lateral release, which can be presented in compact form for the ideal loading history. Example calculations are given for representative metals and plastic ablators. Continuum dynamics (hydrocode) simulations were in good agreement with the algebraic forms. Example applications are presented for several classes of laser-loading experiment, identifying conditions where shocks are desired but not formed, and where long-duration ramps are desired.

  5. Simulation of profile evolution from ramp-up to ramp-down and optimization of tokamak plasma termination with the RAPTOR code

    NASA Astrophysics Data System (ADS)

    Teplukhina, A. A.; Sauter, O.; Felici, F.; Merle, A.; Kim, D.; the TCV Team; the ASDEX Upgrade Team; the EUROfusion MST1 Team

    2017-12-01

    The present work demonstrates the capabilities of the transport code RAPTOR as a fast and reliable simulator of plasma profiles for the entire plasma discharge, i.e. from ramp-up to ramp-down. This code focuses, at this stage, on the simulation of electron temperature and poloidal flux profiles using prescribed equilibrium and some kinetic profiles. In this work we extend the RAPTOR transport model to include a time-varying plasma equilibrium geometry and verify the changes via comparison with ATSRA code simulations. In addition a new ad hoc transport model based on constant gradients and suitable for simulations of L-H and H-L mode transitions has been incorporated into the RAPTOR code and validated with rapid simulations of the time evolution of the safety factor and the electron temperature over the entire AUG and TCV discharges. An optimization procedure for the plasma termination phase has also been developed during this work. We define the goal of the optimization as ramping down the plasma current as fast as possible while avoiding any disruptions caused by reaching physical or technical limits. Our numerical study of this problem shows that a fast decrease of plasma elongation during current ramp-down can help in reducing plasma internal inductance. An early transition from H- to L-mode allows us to reduce the drop in poloidal beta, which is also important for plasma MHD stability and control. This work shows how these complex nonlinear interactions can be optimized automatically using relevant cost functions and constraints. Preliminary experimental results for TCV are demonstrated.

  6. Application of multi-objective nonlinear optimization technique for coordinated ramp-metering

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

    Haj Salem, Habib; Farhi, Nadir; Lebacque, Jean Patrick, E-mail: abib.haj-salem@ifsttar.fr, E-mail: nadir.frahi@ifsttar.fr, E-mail: jean-patrick.lebacque@ifsttar.fr

    2015-03-10

    This paper aims at developing a multi-objective nonlinear optimization algorithm applied to coordinated motorway ramp metering. The multi-objective function includes two components: traffic and safety. Off-line simulation studies were performed on A4 France Motorway including 4 on-ramps.

  7. Guidelines for spacing between freeway ramps.

    DOT National Transportation Integrated Search

    2009-11-01

    Existing geometric design guidance related to interchange ramp spacing in the Texas Roadway Design : Manual and the AASHTOs A Policy on Geometric Design of Highways and Streets (Green Book) is not : speed-dependent even though intuition indicates ...

  8. Static internal performance of single-expansion-ramp nozzles with various combinations of internal geometric parameters

    NASA Technical Reports Server (NTRS)

    Re, R. J.; Leavitt, L. D.

    1984-01-01

    The effects of five geometric design parameters on the internal performance of single-expansion-ramp nozzles were investigated at nozzle pressure ratios up to 10 in the static-test facility of the Langley 16-Foot Transonic Tunnel. The geometric variables on the expansion-ramp surface of the upper flap consisted of ramp chordal angle, ramp length, and initial ramp angle. On the lower flap, the geometric variables consisted of flap angle and flap length. Both internal performance and static-pressure distributions on the centerlines of the upper and lower flaps were obtained for all 43 nozzle configurations tested.

  9. Effect of Valsartan on Cerebellar Adrenomedullin System Dysregulation During Hypertension.

    PubMed

    Figueira, Leticia; Israel, Anita

    2017-02-01

    Adrenomedullin (AM) and its receptors components, calcitonin-receptor-like receptor (CRLR), and receptor activity-modifying protein (RAMP1, RAMP2, and RAMP3) are expressed in cerebellum. Cerebellar AM, AM binding sites and receptor components are altered during hypertension, suggesting a role for cerebellar AM in blood pressure regulation. Thus, we assessed the effect of valsartan, on AM and its receptor components expression in the cerebellar vermis of Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Additionally, we evaluated AM action on superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activity, and thiobarbituric acid reactive substances (TBARS) production in cerebellar vermis. Animals were treated with valsartan or vehicle for 11 days. Rats were sacrificed by decapitation; cerebellar vermis was dissected; and AM, CRLR, RAMP1, RAMP2, and RAMP3 expression was quantified by Western blot analysis. CAT, SOD, and GPx activity was determined spectrophotometrically and blood pressure by non-invasive plethysmography. We demonstrate that AM and RAMP2 expression was lower in cerebellum of SHR rats, while CRLR, RAMP1, and RAMP3 expression was higher than those of WKY rats. AM reduced cerebellar CAT, SOD, GPx activities, and TBARS production in WKY rats, but not in SHR rats. Valsartan reduced blood pressure and reversed the altered expression of AM and its receptors components, as well the loss of AM capacity to reduce antioxidant enzyme activity and TBARS production in SHR rats. These findings demonstrate that valsartan is able to reverse the dysregulation of cerebellar adrenomedullinergic system; and they suggest that altered AM system in the cerebellum could represent the primary abnormality leading to hypertension.

  10. [The effect of hydrophobic surface properties of protein on its resistance to denaturation by organic solvents (using modified alpha-chymotrypsin as an example].

    PubMed

    Kudriashova, E V; Belova, A B; Vinogradov, A A; Mozhaev, V V

    1994-03-01

    Catalytic activity of covalently modified alpha-chymotrypsin in water/cosolvent solutions was investigated. The stability of chymotrypsin increases upon modification with hydrophilic reagents, such as glyceraldehyde, pyrometallic and succinic anhydrides, and glucosamine. Correlation was observed between the protein's stability in organic solvents and the degree of hydrophilization of the protein's surface. The protein is the more stable, the higher are the modification degree and the hydrophilicity of the modifying residue. At a certain critical hydrophilization degree of chymotrypsin a limit of stability is achieved. The stabilization effect can be accounted for by the fact that the interaction between water molecules on the surface and protein's functional groups become stronger in the hydrophilized protein.

  11. Association of the macrophage activating factor (MAF) precursor activity with polymorphism in vitamin D-binding protein.

    PubMed

    Nagasawa, Hideko; Sasaki, Hideyuki; Uto, Yoshihiro; Kubo, Shinichi; Hori, Hitoshi

    2004-01-01

    Serum vitamin D-binding protein (Gc protein or DBP) is a highly expressed polymorphic protein, which is a precursor of the inflammation-primed macrophage activating factor, GcMAF, by a cascade of carbohydrate processing reactions. In order to elucidate the relationship between Gc polymorphism and GcMAF precursor activity, we estimated the phagocytic ability of three homotypes of Gc protein, Gc1F-1F, Gc1S-1S and Gc2-2, through processing of their carbohydrate moiety. We performed Gc typing of human serum samples by isoelectric focusing (IEF). Gc protein from human serum was purified by affinity chromatography with 25-hydroxyvitamin D3-sepharose. A phagocytosis assay of Gc proteins, modified using beta-glycosidase and sialidase, was carried out. The Gc1F-1F phenotype was revealed to possess Galbeta1-4GalNAc linkage by the analysis of GcMAF precursor activity using beta1-4 linkage-specific galactosidase from jack bean. The GcMAF precursor activity of the Gc1F-1F phenotype was highest among three Gc homotypes. The Gc polymorphism and carbohydrate diversity of Gc protein are significant for its pleiotropic effects.

  12. Vibratory high pressure coal feeder having a helical ramp

    DOEpatents

    Farber, Gerald

    1978-01-01

    Apparatus and method for feeding powdered coal from a helical ramp into a high pressure, heated, reactor tube containing hydrogen for hydrogenating the coal and/or for producing useful products from coal. To this end, the helical ramp is vibrated to feed the coal cleanly at an accurately controlled rate in a simple reliable and trouble-free manner that eliminates complicated and expensive screw feeders, and/or complicated and expensive seals, bearings and fully rotating parts.

  13. T-Craft Seabase Ramp Loads Model Test Data Report

    DTIC Science & Technology

    2010-12-01

    INTRODUCTION 1 TEST CONDITION MATRIX 2 MODEL DESCRIPTIONS 9 LMSR Model 15 Ramp Models 17 MODEL TEST SETUP 18 Side-by-Side Hull Configuration 19... INTRODUCTION The Office of Naval Research (ONR) sponsored a multiple bodied seakeeping model test designed to investigate vessel motions and loads on the hinge...C. 3. Side-by-Side configuration 137 Ramp Load cell 1.88 27.49 -CG ft I ^ -Hinged Connection 3.00 from CL to jauge • oad ce LMSR

  14. Decay of the supersonic turbulent wakes from micro-ramps

    NASA Astrophysics Data System (ADS)

    Sun, Z.; Schrijer, F. F. J.; Scarano, F.; van Oudheusden, B. W.

    2014-02-01

    The wakes resulting from micro-ramps immersed in a supersonic turbulent boundary layer at Ma = 2.0 are investigated by means of particle image velocimetry. Two micro-ramps are investigated with height of 60% and 80% of the undisturbed boundary layer, respectively. The measurement domain is placed at the symmetry plane of the ramp and encompasses the range from 10 to 32 ramp heights downstream of the ramp. The decay of the flow field properties is evaluated in terms of time-averaged and root-mean-square (RMS) statistics. In the time-averaged flow field, the recovery from the imparted momentum deficit and the decay of upwash motion are analyzed. The RMS fluctuations of the velocity components exhibit strong anisotropy at the most upstream location and develop into a more isotropic regime downstream. The self-similarity properties of velocity components and fluctuation components along wall-normal direction are followed. The investigation of the unsteady large scale motion is carried out by means of snapshot analysis and by a statistical approach based on the spatial auto-correlation function. The Kelvin-Helmholtz (K-H) instability at the upper shear layer is observed to develop further with the onset of vortex pairing. The average distance between vortices is statistically estimated using the spatial auto-correlation. A marked transition with the wavelength increase is observed across the pairing regime. The K-H instability, initially observed only at the upper shear layer also begins to appear in the lower shear layer as soon as the wake is elevated sufficiently off the wall. The auto-correlation statistics confirm the coherence of counter-rotating vortices from the upper and lower sides, indicating the formation of vortex rings downstream of the pairing region.

  15. The influence of heavy vehicles on traffic dynamics around on-ramp system: Cellular automata approach

    NASA Astrophysics Data System (ADS)

    Kong, Dewen; Guo, Xiucheng; Wu, Dingxin

    Although the on-ramp system has been widely studied, the influence of heavy vehicles is unknown because researchers only investigate the traffic dynamics around on-ramp system under homogeneous traffic conditions, which is different in real-world settings. This paper uses an improved cellular automaton model to study the heterogeneous traffic around on-ramp system. The forward motion rules are improved by considering the differences of driving behavior in different vehicle combinations. The lane change rules are improved by reflecting the aggressive behavior in mandatory lane changes. The phase diagram, traffic flow, capacity and spatial-temporal diagram are analyzed under the influences of heavy vehicles. The results show that by increasing the percentage of heavy vehicles, there will be more severe traffic congestion around on-ramp system, lower saturated flow and capacity. Also, the interactions between main road and on-ramp have been investigated. Increasing the percentage of heavy vehicles at the upstream of the conflict area on the main road or restricting heavy vehicles on the outside lane of the main road will deteriorate the performance of on-ramp. While the main road will have better performance as the percentage of heavy vehicles on the on-ramp increases when the on-ramp inflow rate is not low.

  16. Expanding the chemical toolbox for the synthesis of large and uniquely modified proteins

    NASA Astrophysics Data System (ADS)

    Bondalapati, Somasekhar; Jbara, Muhammad; Brik, Ashraf

    2016-05-01

    Methods to prepare proteins that include a specific modification at a desired position are essential for understanding their cellular functions and physical properties in living systems. Chemical protein synthesis, which relies on the chemoselective ligation of unprotected peptides, enables the preparation of modified proteins that are not easily fabricated by other methods. In contrast to recombinant approaches, chemical synthesis can be used to prepare protein analogues such as D-proteins, which are useful in protein structure determination and the discovery of novel therapeutics. Post-translationally modifying proteins is another example where chemical protein synthesis proved itself as a powerful approach for preparing samples with high homogeneity and in workable quantities. In this Review, we discuss the basic principles of the field, focusing on novel chemoselective peptide ligation approaches such as native chemical ligation and the recent advances based on this method with a proven record of success in the synthesis of highly important protein targets.

  17. High temperature penetrator assembly with bayonet plug and ramp-activated lock

    NASA Technical Reports Server (NTRS)

    Wood, K. E. (Inventor)

    1982-01-01

    A penetration apparatus, for very high temperature applications in which a base plug is inserted into an opening through a bulkhead is described. The base plug has a head shape and is seated against the highest temperature surface of the bulkhead, which may be the skin of the nose cone or other part of a space vehicle intended for nondestructive atmospheric reentry. From the second side of the bulkhead at which the less severe environment is extant, a bayonet plug is inserted into the base plug and engages an internal shoulder at about 90 deg rotation. The bayonet plug has an integral flanged portion and a pair of ramping washers which are located between the flange and the second bulkhead surface with a spacing washer as necessary.

  18. Vehicle operation characteristic under different ramp entrance conditions in underground road: Analysis, simulation and modelling

    NASA Astrophysics Data System (ADS)

    Yao, Qiming; Liu, Shuo; Liu, Yang

    2018-05-01

    An experimental design was used to study the vehicle operation characteristics of different ramp entrance conditions in underground road. With driving simulator, the experimental scenarios include left or right ramp with first, second and third service level, respectively, to collect vehicle speed, acceleration, lateral displacement and location information at the ramp entrance section. By using paired t-test and ANOVA, the influence factors of vehicle operating characteristics are studied. The result shows that effects of ramp layout and mainline traffic environment on vehicle operation characteristics are significant. The regression model of vehicle traveling distance on acceleration lane is established. Suggestions are made for ramp entrance design of underground road.

  19. Programmer's guide to the fuzzy logic ramp metering algorithm : software design, integration, testing, and evaluation

    DOT National Transportation Integrated Search

    2000-02-01

    A Fuzzy Logic Ramp Metering Algorithm was implemented on 126 ramps in the greater Seattle area. This report documents the implementation of the Fuzzy Logic Ramp Metering Algorithm at the Northwest District of the Washington State Department of Transp...

  20. Rural Alaska Mentoring Project (RAMP)

    ERIC Educational Resources Information Center

    Cash, Terry

    2011-01-01

    For over two years the National Dropout Prevention Center (NDPC) at Clemson University has been supporting the Lower Kuskokwim School District (LKSD) in NW Alaska with their efforts to reduce high school dropout in 23 remote Yup'ik Eskimo villages. The Rural Alaska Mentoring Project (RAMP) provides school-based E-mentoring services to 164…

  1. Epigenetic modifications and chromatin loop organization explain the different expression profiles of the Tbrg4, WAP and Ramp3 genes

    USDA-ARS?s Scientific Manuscript database

    Whey Acidic Protein (WAP) gene expression is specific to the mammary gland and regulated by lactogenic hormones to peak during lactation. It differs markedly from the more constitutive expression of the two flanking genes, Ramp3 and Tbrg4. Our results show that the tight regulation of WAP gene expre...

  2. Static internal performance of convergent single-expansion-ramp nozzles with various combinations of internal geometric parameters

    NASA Technical Reports Server (NTRS)

    Bare, E. Ann; Capone, Francis J.

    1989-01-01

    An investigation was conducted in the Static Test Facility of the Langley 16-Foot Transonic Tunnel to determine the effects of five geometric design parameters on the internal performance of convergent single expansion ramp nozzles. The effects of ramp chordal angle, initial ramp angle, flap angle, flap length, and ramp length were determined. All nozzles tested has a nominally constant throat area and aspect ratio. Static pressure distributions along the centerlines of the ramp and flap were also obtained for each configuration. Nozzle pressure ratio was varied up to 10.0 for all configurations.

  3. Sand ramps as palaeoenvironmental archives: Integrating general principles and regional contexts through reanalysis of the Klipkraal Sands, South Africa

    NASA Astrophysics Data System (ADS)

    Rowell, Alexandra L. K.; Thomas, David S. G.; Bailey, Richard M.; Holmes, Peter J.

    2018-06-01

    Sand ramps occur on a continuum of topographically-controlled landforms, ranging from purely aeolian features (climbing/falling dunes) to talus cones and alluvial fans. Sand ramps have been identified as potentially important palaeoenvironmental archives in dryland regions that possess relatively few Quaternary proxy records. Their utility however requires not only good age control of depositional phases but clear identification of process regimes, determined through morphological and sedimentological analyses, with several recent studies indicating the complexities of palaeoenvironmental interpretations and the controls of ramp development (Bateman et al., 2012; Rowell et al., 2018). Klipkraal Sands is a sand ramp on the north-eastern margin of the semi-arid Karoo that has been important for inferences of the extent of southern African Late Quaternary aeolian activity (Thomas et al., 2002). We reanalyse this feature, in the light of both its significance and other recent studies that have inferred extensive southern African LGM aeolian activity (Telfer et al., 2012, 2014). New sedimentological data and twelve OSL dates indicate the Klipkraal Sands formed episodically between 100-0.14 ka, rather than accumulating rapidly, while sedimentological data question the aeolian affinities of the bulk of the feature. Therefore, Klipkraal is reinterpreted as showing no particular affinity to the LGM, with sediments locally sourced with a significant colluvial component. Only the upper historical sediments can be clearly interpreted as aeolian deposits. A complex interplay of processes is suggested, for which a meaningful palaeoenvironmental interpretation cannot be easily defined. This implies that the local geomorphic processes and controls operating on sand ramps need to be established before they can be fully utilised as palaeoenvironmental archives, with implications for their interpretation worldwide.

  4. RAMP: A fault tolerant distributed microcomputer structure for aircraft navigation and control

    NASA Technical Reports Server (NTRS)

    Dunn, W. R.

    1980-01-01

    RAMP consists of distributed sets of parallel computers partioned on the basis of software and packaging constraints. To minimize hardware and software complexity, the processors operate asynchronously. It was shown that through the design of asymptotically stable control laws, data errors due to the asynchronism were minimized. It was further shown that by designing control laws with this property and making minor hardware modifications to the RAMP modules, the system became inherently tolerant to intermittent faults. A laboratory version of RAMP was constructed and is described in the paper along with the experimental results.

  5. Application of Protein Expression Profiling to Screen Chemicals for Androgenic Activity.

    EPA Science Inventory

    Protein expression changes can be used for detection of biomarkers that can be applied diagnostically to screen chemicals for endocrine modifying activity. In this study, Surface Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (SELDI-TOF-MS) coupled with a s...

  6. Study on traffic characteristics for a typical expressway on-ramp bottleneck considering various merging behaviors

    NASA Astrophysics Data System (ADS)

    Sun, Jie; Li, Zhipeng; Sun, Jian

    2015-12-01

    Recurring bottlenecks at freeway/expressway are considered as the main cause of traffic congestion in urban traffic system while on-ramp bottlenecks are the most significant sites that may result in congestion. In this paper, the traffic bottleneck characteristics for a simple and typical expressway on-ramp are investigated by the means of simulation modeling under the open boundary condition. In simulations, the running behaviors of each vehicle are described by a car-following model with a calibrated optimal velocity function, and lane changing actions at the merging section are modeled by a novel set of rules. We numerically derive the traffic volume of on-ramp bottleneck under different upstream arrival rates of mainline and ramp flows. It is found that the vehicles from the ramp strongly affect the pass of mainline vehicles and the merging ratio changes with the increasing of ramp vehicle, when the arrival rate of mainline flow is greater than a critical value. In addition, we clarify the dependence of the merging ratio of on-ramp bottleneck on the probability of lane changing and the length of the merging section, and some corresponding intelligent control strategies are proposed in actual traffic application.

  7. Definition study for temperature control in advanced protein crystal growth

    NASA Technical Reports Server (NTRS)

    Nyce, Thomas A.; Rosenberger, Franz; Sowers, Jennifer W.; Monaco, Lisa A.

    1990-01-01

    Some of the technical requirements for an expedient application of temperature control to advanced protein crystal growth activities are defined. Lysozome was used to study the effects of temperature ramping and temperature gradients for nucleation/dissolution and consecutive growth of sizable crystals and, to determine a prototype temperature program. The solubility study was conducted using equine serum albumin (ESA) which is an extremely stable, clinically important protein due to its capability to bind and transport many different small ions and molecules.

  8. Investigation of ramp injectors for supersonic mixing enhancement

    NASA Technical Reports Server (NTRS)

    Haimovitch, Y.; Gartenberg, E.; Roberts, A. S., Jr.

    1994-01-01

    A comparative study of wall mounted swept ramp injectors fitted with injector nozzles of different shape has been conducted in a constant area duct to explore mixing enhancement techniques for scramjet combustors. Six different injector nozzle inserts, all having equal exit and throat areas, were tested to explore the interaction between the preconditioned fuel jet and the vortical flowfield produced by the ramp: circular nozzle (baseline), nozzle with three downstream facing steps, nozzle with four vortex generators, elliptical nozzle, tapered-slot nozzle, and trapezoidal nozzle. The main flow was air at Mach 2, and the fuel was simulated by air injected at Mach 1.63 or by helium injected at Mach 1.7. Pressure and temperature surveys, combined with Mie and Rayleigh scattering visualization, were used to investigate the flow field. The experiments were compared with three dimensional Navier-Stokes computations. The results indicate that the mixing process is dominated by the streamwise vorticity generated by the ramp, the injectors' inner geometry having a minor effect. It was also found that the injectant/air mixing in the far-field is nearly independent of the injector geometry, molecular weight of the injectant, and the initial convective Mach number.

  9. F-100A on ramp

    NASA Technical Reports Server (NTRS)

    1957-01-01

    North American F-100A Super Sabre on the ramp near the NACA High-Speed Flight Station in 1957. Some airplane characteristics are: Fuselage length, feet 45.64 Wing span, feet Original wing 36.58 Extended wing 38.58 Power Plant: Pratt & Whitney J57-P7 turbojet engine with afterburner Airplane weight, pounds: Basic (without fuel, oil, water, pilot) 19,662

  10. Study of the adhesion of neurodegenerative proteins on plasma-modified and coated polypropylene surfaces.

    PubMed

    Poncin-Epaillard, F; Mille, C; Debarnot, D; Zorzi, W; El Moualij, B; Coudreuse, A; Legeay, G; Quadrio, I; Perret-Liaudet, A

    2012-01-01

    The inner polymeric surface of an ELISA titration well is plasma-modified and coated with different surfactant molecules. The titration of neurodegenerative proteins markers (prion, Tau and β-synuclein), previously demonstrated as more efficient with such modified tubes, is related to the adhesion behaviour of these proteins and their corresponding capture antibodies. The adhesion process is studied in terms of anchoring and specific mechanisms. The proteins and antibodies binding onto such modified surfaces is related to the substrate hydrophilic character calculated from the angle contact measure, to the polymer surface charge measured through the streaming potential determination at different pH and the inner surface roughness determined from AFM images. Furthermore, the influence of the blocking agent used during the ELISA titration is also studied.

  11. Shotgun protein sequencing: assembly of peptide tandem mass spectra from mixtures of modified proteins.

    PubMed

    Bandeira, Nuno; Clauser, Karl R; Pevzner, Pavel A

    2007-07-01

    Despite significant advances in the identification of known proteins, the analysis of unknown proteins by MS/MS still remains a challenging open problem. Although Klaus Biemann recognized the potential of MS/MS for sequencing of unknown proteins in the 1980s, low throughput Edman degradation followed by cloning still remains the main method to sequence unknown proteins. The automated interpretation of MS/MS spectra has been limited by a focus on individual spectra and has not capitalized on the information contained in spectra of overlapping peptides. Indeed the powerful shotgun DNA sequencing strategies have not been extended to automated protein sequencing. We demonstrate, for the first time, the feasibility of automated shotgun protein sequencing of protein mixtures by utilizing MS/MS spectra of overlapping and possibly modified peptides generated via multiple proteases of different specificities. We validate this approach by generating highly accurate de novo reconstructions of multiple regions of various proteins in western diamondback rattlesnake venom. We further argue that shotgun protein sequencing has the potential to overcome the limitations of current protein sequencing approaches and thus catalyze the otherwise impractical applications of proteomics methodologies in studies of unknown proteins.

  12. Colonic vascular conductance increased by Daikenchuto via calcitonin gene-related peptide and receptor-activity modifying protein 1.

    PubMed

    Kono, Toru; Koseki, Takashi; Chiba, Shinichi; Ebisawa, Yoshiaki; Chisato, Naoyuki; Iwamoto, Jun; Kasai, Shinichi

    2008-11-01

    Daikencyuto (DKT) is a traditional Japanese medicine (Kampo) and is a mixture of extract powders from dried Japanese pepper, processed ginger, ginseng radix, and maltose powder and has been used as the treatment of paralytic ileus. DKT may increase gastrointestinal motility by an up-regulation of the calcitonin gene-related peptide (CGRP). CGRP is also the most powerful vasoactive substance. In the present study, we investigated whether DKT has any effect on the colonic blood flow in rats. Experiments were performed on fasted anesthetized and artificially ventilated Wistar rats. Systemic mean arterial blood pressure and heart rate were recorded. Red blood cell flux in colonic blood flow was measured using noncontact laser tissue blood flowmetry, and colonic vascular conductance (CVC) was calculated as the ratio of flux to mean arterial blood pressure. We examined four key physiological mechanisms underlying the response using blocker drugs: CGRP1 receptor blocker (CGRP(8-37)), nitric oxide synthase inhibitor, vasoactive intestinal polypeptide (VIP) receptor blocker ([4-Cl-DPhe6, Leu17]-VIP), and substance P receptor blocker (spantide). Reverse transcription-polymerase chain reaction was used for the detection of mRNA of calcitonin receptor-like receptor, receptor-activity modifying protein 1, the component of CGRP 1 receptor and CGRP. After laparotomy, a cannula was inserted into the proximal colon to administer the DKT and to measure CVC at the distal colon. Intracolonal administration of DKT (10, 100, and 300 mg/kg) increased CVC (basal CVC, 0.10 mL/mmHg) from the first 15-min observation period (0.14, 0.17, and 0.17 mL/mmHg, respectively) and with peak response at either 45 min (0.17 mL/mmHg by 10 mg/kg), or 75 and 60 min (0.23 and 0.21 mL/mmHg by 100 and 300 mg/kg, respectively). CGRP(8-37) completely abolished the DKT-induced hyperemia, whereas nitric oxide synthase inhibitor partially attenuated the DKT-induced hyperemia. [4-Cl-DPhe6, Leu17]-VIP and spantide

  13. Optimizing the current ramp-up phase for the hybrid ITER scenario

    NASA Astrophysics Data System (ADS)

    Hogeweij, G. M. D.; Artaud, J.-F.; Casper, T. A.; Citrin, J.; Imbeaux, F.; Köchl, F.; Litaudon, X.; Voitsekhovitch, I.; the ITM-TF ITER Scenario Modelling Group

    2013-01-01

    The current ramp-up phase for the ITER hybrid scenario is analysed with the CRONOS integrated modelling suite. The simulations presented in this paper show that the heating systems available at ITER allow, within the operational limits, the attainment of a hybrid q profile at the end of the current ramp-up. A reference ramp-up scenario is reached by a combination of NBI, ECCD (UPL) and LHCD. A heating scheme with only NBI and ECCD can also reach the target q profile; however, LHCD can play a crucial role in reducing the flux consumption during the ramp-up phase. The optimum heating scheme depends on the chosen transport model, and on assumptions of parameters like ne peaking, edge Te,i and Zeff. The sensitivity of the current diffusion on parameters that are not easily controlled, shows that development of real-time control is important to reach the target q profile. A first step in that direction has been indicated in this paper. Minimizing resistive flux consumption and optimizing the q profile turn out to be conflicting requirements. A trade-off between these two requirements has to be made. In this paper it is shown that fast current ramp with L-mode current overshoot is at the one extreme, i.e. the optimum q profile at the cost of increased resistive flux consumption, whereas early H-mode transition is at the other extreme.

  14. Safety and operational performance evaluation of four types of exit ramps on Florida's freeways (final report).

    DOT National Transportation Integrated Search

    2010-12-01

    This project mainly focuses on exit ramp performance analysis of safety and operations. In addition, issues of advance guide sign for exit ramp are also mentioned. : Safety analysis evaluates safety performances of different exit ramps used in Florid...

  15. Antifreeze Proteins Modify the Freezing Process In Planta12

    PubMed Central

    Griffith, Marilyn; Lumb, Chelsey; Wiseman, Steven B.; Wisniewski, Michael; Johnson, Robert W.; Marangoni, Alejandro G.

    2005-01-01

    During cold acclimation, winter rye (Secale cereale L. cv Musketeer) plants accumulate antifreeze proteins (AFPs) in the apoplast of leaves and crowns. The goal of this study was to determine whether these AFPs influence survival at subzero temperatures by modifying the freezing process or by acting as cryoprotectants. In order to inhibit the growth of ice, AFPs must be mobile so that they can bind to specific sites on the ice crystal lattice. Guttate obtained from cold-acclimated winter rye leaves exhibited antifreeze activity, indicating that the AFPs are free in solution. Infrared video thermography was used to observe freezing in winter rye leaves. In the absence of an ice nucleator, AFPs had no effect on the supercooling temperature of the leaves. However, in the presence of an ice nucleator, AFPs lowered the temperature at which the leaves froze by 0.3°C to 1.2°C. In vitro studies showed that apoplastic proteins extracted from cold-acclimated winter rye leaves inhibited the recrystallization of ice and also slowed the rate of migration of ice through solution-saturated filter paper. When we examined the possible role of winter rye AFPs in cryoprotection, we found that lactate dehydrogenase activity was higher after freezing in the presence of AFPs compared with buffer, but the same effect was obtained by adding bovine serum albumin. AFPs had no effect on unstacked thylakoid volume after freezing, but did inhibit stacking of the thylakoids, thus indicating a loss of thylakoid function. We conclude that rye AFPs have no specific cryoprotective activity; rather, they interact directly with ice in planta and reduce freezing injury by slowing the growth and recrystallization of ice. PMID:15805474

  16. Effects of ramp reset pulses on the address discharge in a shadow mask plasma display panel

    NASA Astrophysics Data System (ADS)

    Yang, Lanlan; Tu, Yan; Zhang, Xiong; Jiang, Youyan; Zhang, Jian; Wang, Baoping

    2007-05-01

    A two-dimensional self-consistent numerical simulation model is used to analyse the effects of the ramp reset pulses on the address discharge in a shadow mask plasma display panel (SM-PDP). Some basic parameters such as the slope of the ramp pulse and the terminal voltage of the ramp reset period are varied to investigate their effects. The simulation results illustrate that the wall voltage is mainly decided by the terminal voltage and the firing voltage at the end of the ramp reset period. Moreover, the variation of the ramp slope will also bring a few modifications to the wall voltage. The priming particles in the beginning of the addressing period are related to the slope of the ramping down voltage pulse. The simulation results can help us optimize the driving scheme of the SM-PDP.

  17. Behavior of human gastrocnemius muscle fascicles during ramped submaximal isometric contractions.

    PubMed

    Héroux, Martin E; Stubbs, Peter W; Herbert, Robert D

    2016-09-01

    Precise estimates of muscle architecture are necessary to understand and model muscle mechanics. The primary aim of this study was to estimate continuous changes in fascicle length and pennation angle in human gastrocnemius muscles during ramped plantar flexor contractions at two ankle angles. The secondary aim was to determine whether these changes differ between proximal and distal fascicles. Fifteen healthy subjects performed ramped contractions (0-25% MVC) as ultrasound images were recorded from the medial (MG, eight sites) and lateral (LG, six sites) gastrocnemius muscle with the ankle at 90° and 120° (larger angles correspond to shorter muscle lengths). In all subjects, fascicles progressively shortened with increasing torque. MG fascicles shortened 5.8 mm (11.1%) at 90° and 4.5 mm (12.1%) at 120°, whereas LG muscle fascicles shortened 5.1 mm (8.8%) at both ankle angles. MG pennation angle increased 1.4° at 90° and 4.9° at 120°, and LG pennation angle decreased 0.3° at 90° and increased 2.6° at 120°. Muscle architecture changes were similar in proximal and distal fascicles at both ankle angles. This is the first study to describe continuous changes in fascicle length and pennation angle in the human gastrocnemius muscle during ramped isometric contractions. Very similar changes occurred in proximal and distal muscle regions. These findings are relevant to studies modeling active muscle mechanics. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  18. Reinforcement effect of soy protein nanoparticles in amine-modified natural rubber latex

    USDA-ARS?s Scientific Manuscript database

    Mechanical properties of natural rubber reinforced with soy protein nanoparticles are useful for various rubber applications. However, the properties is further improved by improving interactions between soy protein and rubber. A novel method is used to modify particle surface of natural rubber late...

  19. Inhibitory effects of two G protein-coupled receptor kinases on the cell surface expression and signaling of the human adrenomedullin receptor

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

    Kuwasako, Kenji, E-mail: kuwasako@med.miyazaki-u.ac.jp; Sekiguchi, Toshio; Nagata, Sayaka

    2016-02-19

    Receptor activity-modifying protein 2 (RAMP2) enables the calcitonin receptor-like receptor (CLR, a family B GPCR) to form the type 1 adrenomedullin receptor (AM{sub 1} receptor). Here, we investigated the effects of the five non-visual GPCR kinases (GRKs 2 through 6) on the cell surface expression of the human (h)AM{sub 1} receptor by cotransfecting each of these GRKs into HEK-293 cells that stably expressed hRAMP2. Flow cytometric analysis revealed that when coexpressed with GRK4 or GRK5, the cell surface expression of the AM{sub 1} receptor was markedly decreased prior to stimulation with AM, thereby attenuating both the specific [{sup 125}I]AM binding andmore » AM-induced cAMP production. These inhibitory effects of both GRKs were abolished by the replacement of the cytoplasmic C-terminal tail (C-tail) of CLR with that of the calcitonin receptor (a family B GPCR) or β{sub 2}-adrenergic receptor (a family A GPCR). Among the sequentially truncated CLR C-tail mutants, those lacking the five residues 449–453 (Ser-Phe-Ser-Asn-Ser) abolished the inhibition of the cell surface expression of CLR via the overexpression of GRK4 or GRK5. Thus, we provided new insight into the function of GRKs in agonist-unstimulated GPCR trafficking using a recombinant AM{sub 1} receptor and further determined the region of the CLR C-tail responsible for this GRK function. - Highlights: • We discovered a novel function of GRKs in GPCR trafficking using human CLR/RAMP2. • GRKs 4 and 5 markedly inhibited the cell surface expression of human CLR/RAMP2. • Both GRKs exhibited highly significant receptor signaling inhibition. • Five residues of the C-terminal tail of CLR govern this function of GRKs.« less

  20. Traffic dynamics of an on-ramp system with a cellular automaton model

    NASA Astrophysics Data System (ADS)

    Li, Xin-Gang; Gao, Zi-You; Jia, Bin; Jiang, Rui

    2010-06-01

    This paper uses the cellular automaton model to study the dynamics of traffic flow around an on-ramp with an acceleration lane. It adopts a parameter, which can reflect different lane-changing behaviour, to represent the diversity of driving behaviour. The refined cellular automaton model is used to describe the lower acceleration rate of a vehicle. The phase diagram and the capacity of the on-ramp system are investigated. The simulation results show that in the single cell model, the capacity of the on-ramp system will stay at the highest flow of a one lane system when the driver is moderate and careful; it will be reduced when the driver is aggressive. In the refined cellular automaton model, the capacity is always reduced even when the driver is careful. It proposes that the capacity drop of the on-ramp system is caused by aggressive lane-changing behaviour and lower acceleration rate.

  1. Third Expert Consultation on RAMP (RAMP III) (Helsinki, Finland, September 13, 15 and 20, 1986). Final Report.

    ERIC Educational Resources Information Center

    United Nations Educational, Scientific and Cultural Organization, Paris (France). General Information Programme.

    Organized for the United Nations Educational, Scientific, and Cultural Organization (Unesco) by contract with the International Council on Archives (ICA), this meeting concerning the Records and Archives Management Programme (RAMP) was attended by 14 experts invited from Unesco member countries. Following a brief introduction, summaries are…

  2. Multiphysics modelling of the separation of suspended particles via frequency ramping of ultrasonic standing waves.

    PubMed

    Trujillo, Francisco J; Eberhardt, Sebastian; Möller, Dirk; Dual, Jurg; Knoerzer, Kai

    2013-03-01

    A model was developed to determine the local changes of concentration of particles and the formations of bands induced by a standing acoustic wave field subjected to a sawtooth frequency ramping pattern. The mass transport equation was modified to incorporate the effect of acoustic forces on the concentration of particles. This was achieved by balancing the forces acting on particles. The frequency ramping was implemented as a parametric sweep for the time harmonic frequency response in time steps of 0.1s. The physics phenomena of piezoelectricity, acoustic fields and diffusion of particles were coupled and solved in COMSOL Multiphysics™ (COMSOL AB, Stockholm, Sweden) following a three step approach. The first step solves the governing partial differential equations describing the acoustic field by assuming that the pressure field achieves a pseudo steady state. In the second step, the acoustic radiation force is calculated from the pressure field. The final step allows calculating the locally changing concentration of particles as a function of time by solving the modified equation of particle transport. The diffusivity was calculated as function of concentration following the Garg and Ruthven equation which describes the steep increase of diffusivity when the concentration approaches saturation. However, it was found that this steep increase creates numerical instabilities at high voltages (in the piezoelectricity equations) and high initial particle concentration. The model was simplified to a pseudo one-dimensional case due to computation power limitations. The predicted particle distribution calculated with the model is in good agreement with the experimental data as it follows accurately the movement of the bands in the centre of the chamber. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

  3. Changes of hydrodynamic parameters on mountain stream bed within the block ramp influence and possibility of their use for integrated river management

    NASA Astrophysics Data System (ADS)

    Radecki-Pawlik, Artur; Plesiński, Karol

    2016-04-01

    In modern river management practices and philosophy one can notice coming more into use ecological friendly hydraulic structures. Those, which are especially needed for river training works, as far as expectation of Water Framework Directive is concerned, are block ramps which are hydraulic structures working similar to riffles known very well from fluvial geomorphology studies and are natural features in streams and rivers. What is important well designed block ramps do not stop fish and invertebrates against migrating, provide natural and esthetical view being built within the river channel, still working as hydraulic engineering structures and might be used in river management in different river ecosystems. The main aim of the research was to describe changes of values of hydrodynamics parameters upstream and downstream of the block ramps and to find out their influence on hydrodynamics of the stream. The study was undertaken on the Porębianka River in the Gorce Mountains, Polish Carpathians. Observed hydrodynamic parameters within the reach of the block ramps depend on the location of measuring point and the influence of individual part of the structure. We concluded that: 1. Hydrodynamic parameters close to block ramps depend on the location of the measurement points in relation to particular elements of the structure; 2. The highest value of velocities don't cause the highest force values, which acting on the bed of the watercourse, because they are rather related to the water level of the channel; 3. The values of mean velocities, shear velocities and shear stresses were similar upstream and downstream the block ramps, which means that the structures stabilize the river bed. This study was performed within the scope of the Science Activity money from Ministry of High Education and Young Scientist's Activity Money of Department of Hydraulics Engineering and Geotechnique, University of Agriculture, Cracow, Poland

  4. Effect of microfluidized and stearic acid modified soy protein in natural rubber

    USDA-ARS?s Scientific Manuscript database

    Microfluidized and stearic acid modified soy protein aggregates were used to reinforced natural rubber. The size of soy protein particles was reduced with a microfluidizing and ball milling process. Filler size reduction with longer ball milling time tends to increase tensile strength of the rubber ...

  5. Exploring how sand ramps respond to Quaternary environmental change in Southern Africa

    NASA Astrophysics Data System (ADS)

    Rowell, Alex; Thomas, David; Bailey, Richard

    2014-05-01

    The current climate of southern Africa is particularly complex and interesting due to the interaction of several climatic systems. However, reconstructions of how these systems behaved in the past, and how the environment responded, have been hampered by a general paucity of records and poor chronological control. Sand ramps may provide the potential to improve palaeoenvironmental reconstructions of southern Africa (and beyond). Formed against a topographic barrier, sand ramps include a combination of aeolian, fluvial and colluvial deposits in varying proportions. Therefore, they have the potential to record changes in moisture availability, circulation patterns and sediment supply which can be independently dated using luminescence dating. Nevertheless relatively little attention has been paid to these features and thus the environmental controls on their formation are not yet fully understood. In particular, there is debate as to whether they reflect deposition during a 'window of opportunity' in which high-magnitude, low-frequency events are recorded (Bateman et al. 2012) or whether they record more gradual, cyclic climate change (Bertram, 2003) or even if there is a uniform control on their formation. This research aims to investigate how sand ramps respond to environmental change and what they can tell us about the paleoenvironment of southern Africa. This poster displays preliminary results based on initial field investigation. This confirmed sand ramps to be ubiquitous in southern Africa and that they record a complex interaction of aeolian, fluvial and colluvial deposits which appears to differ between sand ramps. Preliminary luminescence dating results and sedimentology are displayed for two sand ramps, one from south west Namibia the other from the Karoo region of South Africa.

  6. Sonomyographic responses during voluntary isometric ramp contraction of the human rectus femoris muscle.

    PubMed

    Chen, Xin; Zheng, Yong-Ping; Guo, Jing-Yi; Zhu, Zhenyu; Chan, Shing-Chow; Zhang, Zhiguo

    2012-07-01

    This paper aims to investigate the relationship between torque and muscle morphological change, which is derived from ultrasound image sequence and termed as sonomyography (SMG), during isometric ramp contraction of the rectus femoris (RF) muscle, and to further compare SMG with the electromyography (EMG) and mechanomyography (MMG), which represent the electrical and mechanical activities of the muscle. Nine subjects performed isometric ramp contraction of knee up to 90% of the maximal voluntary contraction (MVC) at speeds of 45, 22.5 and 15% MVC/s, and EMG, MMG and ultrasonography were simultaneously recorded from the RF muscle. Cross-sectional area, which was referred to as SMG, was automatically extracted from continuously captured ultrasound images using a newly developed image tracking algorithm. Polynomial regression analyses were applied to fit the EMG/MMG/SMG-to-torque relationships, and the regression coefficients of EMG, MMG, and SMG were compared. Moreover, the effect of contraction speed on SMG/EMG/MMG-to-torque relationships was tested by pair-wise comparisons of the mean relationship curves at different speeds for EMG, MMG and SMG. The results show that continuous SMG could provide important morphological parameters of continuous muscle contraction. Compared with EMG and MMG, SMG exhibits different changing patterns with the increase of torque during voluntary isometric ramp contraction, and it is less influenced by the contraction speed.

  7. Guidelines for Evaluation of Ramp Signaling Deployments in a Real-Time Operations Environment

    DOT National Transportation Integrated Search

    2017-12-01

    State agencies have developed warrants and guidelines for the identification of on-ramps for metering. However, these warrants only consider recurrent traffic conditions in the vicinity of each on-ramp without considering the need to meter multiple r...

  8. The Effect of Micro-ramps on Supersonic Flow over a Forward-Facing Step

    NASA Astrophysics Data System (ADS)

    Zhang, Qing-Hu; Yi, Shi-He; Zhu, Yang-Zhu; Chen, Zhi; Wu, Yu

    2013-04-01

    The effect of micro-ramp control on fully developed turbulent flow over a forward-facing step (FFS) is investigated in a supersonic low-noise wind tunnel at Mach number 3 using nano-tracer planar laser scattering (NPLS) and supersonic particle image velocimetry (PIV) techniques. High spatiotemporal resolution images and the average velocity profiles of supersonic flow over the FFS with and without the control of the micro-ramps are captured. The fine structures of both cases, including the coherent structures of fully developed boundary layer and the large-scale hairpin-like vortices originated from the micro-ramps as well as the interaction of shock waves with the large-scale structures, are revealed and compared. Based on the time-correlation images, the temporal and spatial evolutionary characteristics of the coherent structures are investigated. It is beneficial to understand the dynamic mechanisms of the separated flow and the control mechanisms of the micro-ramps. The size of the separation region is determined by the NPLS and PIV. The results indicate that the control of the micro-ramps is capable of delaying the separation and diminishing the extent of recirculation zone.

  9. Improving short-term forecasting during ramp events by means of Regime-Switching Artificial Neural Networks

    NASA Astrophysics Data System (ADS)

    Gallego, C.; Costa, A.; Cuerva, A.

    2010-09-01

    Since nowadays wind energy can't be neither scheduled nor large-scale storaged, wind power forecasting has been useful to minimize the impact of wind fluctuations. In particular, short-term forecasting (characterised by prediction horizons from minutes to a few days) is currently required by energy producers (in a daily electricity market context) and the TSO's (in order to keep the stability/balance of an electrical system). Within the short-term background, time-series based models (i.e., statistical models) have shown a better performance than NWP models for horizons up to few hours. These models try to learn and replicate the dynamic shown by the time series of a certain variable. When considering the power output of wind farms, ramp events are usually observed, being characterized by a large positive gradient in the time series (ramp-up) or negative (ramp-down) during relatively short time periods (few hours). Ramp events may be motivated by many different causes, involving generally several spatial scales, since the large scale (fronts, low pressure systems) up to the local scale (wind turbine shut-down due to high wind speed, yaw misalignment due to fast changes of wind direction). Hence, the output power may show unexpected dynamics during ramp events depending on the underlying processes; consequently, traditional statistical models considering only one dynamic for the hole power time series may be inappropriate. This work proposes a Regime Switching (RS) model based on Artificial Neural Nets (ANN). The RS-ANN model gathers as many ANN's as different dynamics considered (called regimes); a certain ANN is selected so as to predict the output power, depending on the current regime. The current regime is on-line updated based on a gradient criteria, regarding the past two values of the output power. 3 Regimes are established, concerning ramp events: ramp-up, ramp-down and no-ramp regime. In order to assess the skillness of the proposed RS-ANN model, a single

  10. Global functions of extracellular, transmembrane and cytoplasmic domains of organic solute transporter β-subunit.

    PubMed

    Christian, Whitney V; Hinkle, Patricia M

    2017-05-25

    Transport of bile acids across the basolateral membrane of the intestinal enterocyte is carried out by the organic solute transporter (Ost) composed of a seven-transmembrane domain (TMD) subunit (Ostα) and an ancillary single TMD subunit (Ostβ). Although previous investigations have demonstrated the importance of the TMD of Ostβ for its activity, further studies were conducted to assess the contributions of other regions of the Ostβ subunit. Transport activity was retained when Ostβ was truncated to contain only the TMD with 15 additional residues on each side and co-expressed with Ostα, whereas shorter fragments were inactive. To probe the broader functions of Ostβ segments, chimeric proteins were constructed in which N-terminal, TMD or C-terminal regions of Ostβ were fused to corresponding regions of receptor activity-modifying protein (RAMP1), a single TMD protein required by several seven-TMD G-protein-coupled receptors including the calcitonin receptor-like receptor (CLR). Ostβ/RAMP1 chimeras were expressed with Ostα and CLR. As expected, replacing the Ostβ TMD abolished transport activity; however, replacing either the entire N-terminal or entire C-terminal domain of Ostβ with RAMP1 sequences did not prevent plasma membrane localization or the ability to support [ 3 H]taurocholate uptake. Co-immunoprecipitation experiments revealed that the C-terminus of Ostβ is a previously unrecognized site of interaction with Ostα. All chimeras containing N-terminal RAMP1 segments allowed co-expressed CLR to respond to agonists with strong increases in cyclic AMP. These results provide new insights into the structure and function of the heteromeric Ost transporter complex. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  11. [Adsorption of perfluorooctanesulfonate (PFOS) onto modified activated carbons].

    PubMed

    Tong, Xi-Zhen; Shi, Bao-You; Xie, Yue; Wang, Dong-Sheng

    2012-09-01

    Modified coal and coconut shell based powdered activated carbons (PACs) were prepared by FeCl3 and medium power microwave treatment, respectively. Batch experiments were carried out to evaluate the characteristics of adsorption equilibrium and kinetics of perfluorooctanesulfonate (PFOS) onto original and modified PACs. Based on pore structure and surface functional groups characterization, the adsorption behaviors of modified and original PACs were compared. The competitive adsorption of humic acid (HA) and PFOS on original and modified coconut shell PACs were also investigated. Results showed that both Fe3+ and medium power microwave treatments changed the pore structure and surface functional groups of coal and coconut shell PACs, but the changing effects were different. The adsorption of PFOS on two modified coconut shell-based PACs was significantly improved. While the adsorption of modified coal-based activated carbons declined. The adsorption kinetics of PFOS onto original and modified coconut shell-based activated carbons were the same, and the time of reaching adsorption equilibrium was about 6 hours. In the presence of HA, the adsorption of PFOS by modified PAC was reduced but still higher than that of the original.

  12. X-36 on Ramp Viewed from Above

    NASA Image and Video Library

    1997-07-16

    This look-down view of the X-36 Tailless Fighter Agility Research Aircraft on the ramp at NASA’s Dryden Flight Research Center, Edwards, California, clearly shows the unusual wing and canard design of the remotely-piloted aircraft.

  13. Effectiveness of a multidisciplinary risk assessment and management programme-diabetes mellitus (RAMP-DM) on patient-reported outcomes.

    PubMed

    Wan, Eric Yuk Fai; Fung, Colman Siu Cheung; Wong, Carlos King Ho; Choi, Edmond Pui Hang; Jiao, Fang Fang; Chan, Anca Ka Chun; Chan, Karina Hiu Yen; Lam, Cindy Lo Kuen

    2017-02-01

    Little is known about how the patient-reported outcomes is influenced by multidisciplinary-risk-assessment-and-management-programme for patients with diabetes mellitus (RAMP-DM). This paper aims to evaluate the effectiveness of RAMP-DM on patient-reported outcomes. This was a prospective longitudinal study on 1039 diabetes mellitus patients (714/325 RAMP-DM/non-RAMP-DM) managed in primary care setting. 536 and 402 RAMP-DM participants, and 237 and 187 non-RAMP-DM participants were followed up at 12 and 24 months with completed survey, respectively. Patient-reported outcomes included health-related quality of life, change in global health condition and patient enablement measured by Short Form-12 Health Survey version-2 (SF-12v2), Global Rating Scale, Patient Enablement Instrument respectively. The effects of RAMP-DM on patient-reported outcomes were evaluated by mixed effect models. Subgroup analysis was performed by stratifying haemoglobin A1c (HbA1c) (optimal HbA1c < 7 % and suboptimal HbA1c ≥ 7 %). RAMP-DM with suboptimal HbA1c was associated with greater improvement in SF-12v2 physical component summary score at 12-month (coefficient:3.80; P-value < 0.05) and 24-month (coefficient:3.82;P-value < 0.05), more likely to feel more enabled at 12-month (odds ratio: 2.57; P-value < 0.05), and have improved in GRS at 24-month (odds ratio:4.05; P-value < 0.05) compared to non-RAMP-DM participants. However, there was no significant difference in patient-reported outcomes between RAMP-DM and non-RAMP-DM participants with optimal HbA1c. Participation in RAMP-DM is effective in improving physical component of HRQOL, Global Rating Scale and patient enablement among diabetes mellitus patients with suboptimal HbA1c, but not in those with optimal HbA1c. Patients with sub-optimal diabetes mellitus control should be the priority target population for RAMP-DM. This observational study design may have potential bias in the characteristics between

  14. Favorable Influence of Hydrophobic Surfaces on Protein Structure in Porous Organically-modified Silica Glasses

    PubMed Central

    Menaa, Bouzid; Herrero, Mar; Rives, Vicente; Lavrenko, Mayya; Eggers, Daryl K.

    2008-01-01

    Organically-modified siloxanes were used as host materials to examine the influence of surface chemistry on protein conformation in a crowded environment. The sol-gel materials were prepared from tetramethoxysilane and a series of monosubstituted alkoxysilanes, RSi(OR′)3, featuring alkyl groups of increasing chain length in the R-position. Using circular dichroism spectroscopy in the far-UV region, apomyoglobin was found to transit from an unfolded state to a native-like helical state as the content of the hydrophobic precursor increased from 0–15%. At a fixed molar content of 5% RSi(OR’)3, the helical structure of apomyoglobin increased with the chain length of the R-group, i.e. methyl < ethyl < n-propyl < n-butyl < n-hexyl. This trend also was observed for the tertiary structure of ribonuclease A, suggesting that protein folding and biological activity are sensitive to the hydrophilic/hydrophobic balance of neighboring surfaces. The observed changes in protein structure did not correlate with total surface area or the average pore size of the modified glasses, but scanning electron microscopy images revealed an interesting relationship between surface morphology and alkyl chain length. The unexpected benefit of incorporating a low content of hydrophobic groups into a hydrophilic surface may lead to materials with improved biocompatibility for use in biosensors and implanted devices. PMID:18359512

  15. The value of improved wind power forecasting: Grid flexibility quantification, ramp capability analysis, and impacts of electricity market operation timescales

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

    Wang, Qin; Wu, Hongyu; Florita, Anthony R.

    The value of improving wind power forecasting accuracy at different electricity market operation timescales was analyzed by simulating the IEEE 118-bus test system as modified to emulate the generation mixes of the Midcontinent, California, and New England independent system operator balancing authority areas. The wind power forecasting improvement methodology and error analysis for the data set were elaborated. Production cost simulation was conducted on the three emulated systems with a total of 480 scenarios, considering the impacts of different generation technologies, wind penetration levels, and wind power forecasting improvement timescales. The static operational flexibility of the three systems was comparedmore » through the diversity of generation mix, the percentage of must-run baseload generators, as well as the available ramp rate and the minimum generation levels. The dynamic operational flexibility was evaluated by the real-time upward and downward ramp capacity. Simulation results show that the generation resource mix plays a crucial role in evaluating the value of improved wind power forecasting at different timescales. In addition, the changes in annual operational electricity generation costs were mostly influenced by the dominant resource in the system. Lastly, the impacts of pumped-storage resources, generation ramp rates, and system minimum generation level requirements on the value of improved wind power forecasting were also analyzed.« less

  16. The value of improved wind power forecasting: Grid flexibility quantification, ramp capability analysis, and impacts of electricity market operation timescales

    DOE PAGES

    Wang, Qin; Wu, Hongyu; Florita, Anthony R.; ...

    2016-11-11

    The value of improving wind power forecasting accuracy at different electricity market operation timescales was analyzed by simulating the IEEE 118-bus test system as modified to emulate the generation mixes of the Midcontinent, California, and New England independent system operator balancing authority areas. The wind power forecasting improvement methodology and error analysis for the data set were elaborated. Production cost simulation was conducted on the three emulated systems with a total of 480 scenarios, considering the impacts of different generation technologies, wind penetration levels, and wind power forecasting improvement timescales. The static operational flexibility of the three systems was comparedmore » through the diversity of generation mix, the percentage of must-run baseload generators, as well as the available ramp rate and the minimum generation levels. The dynamic operational flexibility was evaluated by the real-time upward and downward ramp capacity. Simulation results show that the generation resource mix plays a crucial role in evaluating the value of improved wind power forecasting at different timescales. In addition, the changes in annual operational electricity generation costs were mostly influenced by the dominant resource in the system. Lastly, the impacts of pumped-storage resources, generation ramp rates, and system minimum generation level requirements on the value of improved wind power forecasting were also analyzed.« less

  17. Competitive Protein Adsorption on Polysaccharide and Hyaluronate Modified Surfaces

    PubMed Central

    Ombelli, Michela; Costello, Lauren; Postle, Corinne; Anantharaman, Vinod; Meng, Qing Cheng; Composto, Russell J.; Eckmann, David M.

    2011-01-01

    We measured adsorption of bovine serum albumin (BSA) and fibrinogen (Fg) onto six distinct bare and dextran- and hyaluronate-modified silicon surfaces created using two dextran grafting densities and three hyaluronic acid (HA) sodium salts derived from human umbilical cord, rooster comb and streptococcus zooepidemicus. Film thickness and surface morphology depended on HA molecular weight and concentration. BSA coverage was enhanced on surfaces upon competitive adsorption of BSA:Fg mixtures. Dextranization differentially reduced protein adsorption onto surfaces based on oxidation state. Hyaluronization was demonstrated to provide the greatest resistance to protein coverage, equivalent to that of the most resistant dextranized surface. Resistance to protein adsorption was independent of the type of hyaluronic acid utilized. With changing bulk protein concentration from 20 to 40 µg ml−1 for each species, Fg coverage on silicon increased by 4×, whereas both BSA and Fg adsorption on dextran and HA were far less dependent of protein bulk concentration. PMID:21623481

  18. Photo-induced conjugation of tetrazoles to modified and native proteins.

    PubMed

    Siti, Winna; Khan, Amit Kumar; de Hoog, Hans-Peter M; Liedberg, Bo; Nallani, Madhavan

    2015-03-21

    Bio-orthogonal chemistry has been widely used for conjugation of polymer molecules to proteins. Here, we demonstrate the conjugation of polyethylene glycol (PEG) to bovine beta-lactoglobulin (BLG) by photo-induced cyclo-addition of tetrazole-appended PEG and allyl-modified BLG. During the course of the investigation, a significant side-reaction was found to occur for the conjugation of PEG-tetrazole to native BLG. Further exploration of the underlying chemistry reveals that the presence of a tryptophan residue is sufficient for conjugation of tetrazole-modified molecules.

  19. Self-Assembled Modified Soy Protein/Dextran Nanogel Induced by Ultrasonication as a Delivery Vehicle for Riboflavin.

    PubMed

    Jin, Bei; Zhou, Xiaosong; Li, Xiangzhong; Lin, Weiqin; Chen, Guangbin; Qiu, Riji

    2016-03-15

    A simple and green approach was developed to produce a novel nanogel via self-assembly of modified soy protein and dextran, to efficiently deliver riboflavin. First, modified soy protein was prepared by heating denaturation at 60 °C for 30 min or Alcalase hydrolysis for 40 min. Second, modified soy protein was mixed with dextran and ultrasonicated for 70 min so as to assemble nanogels. The modified soy protein-dextran nanogels were characterized by Fourier-transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) and ζ-potential studies to confirm the formation of NGs. Transmission electron microscopy (TEM) revealed the NGs to be spherical with core-shell structures, in the range of 32-40 nm size. The nanogels were stable against various environmental conditions. Furthermore, the particle size of the nanogels hardly changed with the incorporation of riboflavin. The encapsulation efficiency of nanogels was found to be up to 65.9% at a riboflavin concentration of 250 μg/mL. The nanogels exhibited a faster release in simulated intestine fluid (SIF) compared with simulated gastric fluid (SGF). From the results obtained it can be concluded that modified soy protein-dextran nanogels can be considered a promising carrier for drugs and other bioactive molecule delivery purposes.

  20. Power ramp induced iodine and cesium redistribution in LWR fuel rods

    NASA Astrophysics Data System (ADS)

    Sontheimer, F.; Vogl, W.; Ruyter, I.; Markgraf, J.

    1980-01-01

    Volatile fission product migration in LWR fuel rods which are power ramped above a certain threshold beyond the envelope of their previous power history, plays an important role in stress corrosion cracking of Zircaloy. This may cause fuel rods to fail already at stresses below the yield strength. In the HFR, Petten, many power ramp experiments have been performed with subsequent examination of the ramped rods for fission product distribution. This study describes the measurement of iodine and cesium distribution using γ-spectroscopy of I-131 and Cs-137. An evaluation method is presented which makes the determination of absolute amounts of I/Cs feasible. It is shown that a threshold for I/Cs redistribution exists beyond which it depends strongly on local fuel rod power and fuel type.

  1. Detectable Warning Surfaces at Curb Ramps.

    ERIC Educational Resources Information Center

    Hauger, J. S.; And Others

    1996-01-01

    Four tests evaluated the need for and effectiveness of detectable warning surfaces at curb ramps for pedestrians with blindness. Results found that the effectiveness of the detectable warning surfaces depended on other aspects of the design of the intersections and on factors such as the density of traffic and the traveler's skills. (CR)

  2. Targeted sonodynamic therapy using protein-modified TiO2 nanoparticles.

    PubMed

    Ninomiya, Kazuaki; Ogino, Chiaki; Oshima, Shuhei; Sonoke, Shiro; Kuroda, Shun-ichi; Shimizu, Nobuaki

    2012-05-01

    Our previous study suggested new sonodynamic therapy for cancer cells based on the delivery of titanium dioxide (TiO(2)) nanoparticles (NPs) modified with a protein specifically recognizing target cells and subsequent generation of hydroxyl radicals from TiO(2) NPs activated by external ultrasound irradiation (called TiO(2)/US treatment). The present study first examined the uptake behavior of TiO(2) NPs modified with pre-S1/S2 (model protein-recognizing hepatocytes) by HepG2 cells for 24h. It took 6h for sufficient uptake of the TiO(2) NPs by the cells. Next, the effect of the TiO(2)/US treatment on HepG2 cell growth was examined for 96 h after the 1 MHz ultrasound was irradiated (0.1 W/cm(2), 30s) to the cells which incorporated the TiO(2) NPs. Apoptosis was observed at 6h after the TiO(2)/US treatment. Although no apparent cell-injury was observed until 24h after the treatment, the viable cell concentration had deteriorated to 46% of the control at 96 h. Finally, the TiO(2)/US treatment was applied to a mouse xenograft model. The pre-S1/S2-immobilized TiO(2) (0.1mg) was directly injected into tumors, followed by 1 MHz ultrasound irradiation at 1.0 W/cm(2) for 60s. As a result of the treatment repeated five times within 13 days, tumor growth could be hampered up to 28 days compared with the control conditions. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. Multilayer Choline Phosphate Molecule Modified Surface with Enhanced Cell Adhesion but Resistance to Protein Adsorption.

    PubMed

    Chen, Xingyu; Yang, Ming; Liu, Botao; Li, Zhiqiang; Tan, Hong; Li, Jianshu

    2017-08-22

    Choline phosphate (CP), which is a new zwitterionic molecule, and has the reverse order of phosphate choline (PC) and could bind to the cell membrane though the unique CP-PC interaction. Here we modified a glass surface with multilayer CP molecules using surface-initiated atom-transfer radical polymerization (SI-ATRP) and the ring-opening method. Polymeric brushes of (dimethylamino)ethyl methacrylate (DMAEMA) were synthesized by SI-ATRP from the glass surface. Then the grafted PDMAEMA brushes were used to introduce CP groups to fabricate the multilayer CP molecule modified surface. The protein adsorption experiment and cell culture test were used to evaluate the biocompatibility of the modified surfaces by using human umbilical veinendothelial cells (HUVECs). The protein adsorption results demonstrated that the multilayer CP molecule decorated surface could prevent the adsorption of fibrinogen and serum protein. The adhesion and proliferation of cells were improved significantly on the multilayer CP molecule modified surface. Therefore, the biocompatibility of the material surface could be improved by the modified multilayer CP molecule, which exhibits great potential for biomedical applications, e.g., scaffolds in tissue engineering.

  4. Structure function analysis of two-scale Scalar Ramps. Part I: Theory and Modeling

    USDA-ARS?s Scientific Manuscript database

    Structure functions are used to study the dissipation and inertial range scales of turbulent energy, to parameterize remote turbulence measurements, and to characterize ramp features in the turbulent field. The ramp features are associated with turbulent coherent structures, which dominate energy an...

  5. The gap junction channel protein connexin 43 is covalently modified and regulated by SUMOylation.

    PubMed

    Kjenseth, Ane; Fykerud, Tone A; Sirnes, Solveig; Bruun, Jarle; Yohannes, Zeremariam; Kolberg, Matthias; Omori, Yasufumi; Rivedal, Edgar; Leithe, Edward

    2012-05-04

    SUMOylation is a posttranslational modification in which a member of the small ubiquitin-like modifier (SUMO) family of proteins is conjugated to lysine residues in specific target proteins. Most known SUMOylation target proteins are located in the nucleus, but there is increasing evidence that SUMO may also be a key determinant of many extranuclear processes. Gap junctions consist of arrays of intercellular channels that provide direct transfer of ions and small molecules between adjacent cells. Gap junction channels are formed by integral membrane proteins called connexins, of which the best-studied isoform is connexin 43 (Cx43). Here we show that Cx43 is posttranslationally modified by SUMOylation. The data suggest that the SUMO system regulates the Cx43 protein level and the level of functional Cx43 gap junctions at the plasma membrane. Cx43 was found to be modified by SUMO-1, -2, and -3. Evidence is provided that the membrane-proximal lysines at positions 144 and 237, located in the Cx43 intracellular loop and C-terminal tail, respectively, act as SUMO conjugation sites. Mutations of lysine 144 or lysine 237 resulted in reduced Cx43 SUMOylation and reduced Cx43 protein and gap junction levels. Altogether, these data identify Cx43 as a SUMOylation target protein and represent the first evidence that gap junctions are regulated by the SUMO system.

  6. Neuronal sphingolipidoses: Membrane lipids and sphingolipid activator proteins regulate lysosomal sphingolipid catabolism.

    PubMed

    Sandhoff, Konrad

    2016-11-01

    Glycosphingolipids and sphingolipids of cellular plasma membranes (PMs) reach luminal intra-lysosomal vesicles (LVs) for degradation mainly by pathways of endocytosis. After a sorting and maturation process (e.g. degradation of sphingomyelin (SM) and secretion of cholesterol), sphingolipids of the LVs are digested by soluble enzymes with the help of activator (lipid binding and transfer) proteins. Inherited defects of lipid-cleaving enzymes and lipid binding and transfer proteins cause manifold and fatal, often neurodegenerative diseases. The review summarizes recent findings on the regulation of sphingolipid catabolism and cholesterol secretion from the endosomal compartment by lipid modifiers, an essential stimulation by anionic membrane lipids and an inhibition of crucial steps by cholesterol and SM. Reconstitution experiments in the presence of all proteins needed, hydrolase and activator proteins, reveal an up to 10-fold increase of ganglioside catabolism just by the incorporation of anionic lipids into the ganglioside carrying membranes, whereas an additional incorporation of cholesterol inhibits GM2 catabolism substantially. It is suggested that lipid and other low molecular modifiers affect the genotype-phenotype relationship observed in patients with lysosomal diseases. Copyright © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  7. Dendrimer enriched single-use aptasensor for impedimetric detection of activated protein C.

    PubMed

    Erdem, Arzum; Congur, Gulsah

    2014-05-01

    A novel impedimetric aptasensor for detection of human activated protein C (APC) was introduced for the first time in the present study. An enhanced sensor response was obtained using poly(amidoamine) (PAMAM) dendrimer having 16 succinamic acid surface groups (generation 2, G2-PS), that was modified onto the surface of screen printed graphite electrode (G2-PS/SPE). An amino modified DNA aptamer was then immobilized onto the surface of G2-PS modified SPE. The selective interaction of APT with its cognate protein, APC was investigated using different electrochemical techniques; differential pulse voltammetry (DPV), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The microscopic characterization was consecutively performed before/after each modification/interaction step using scanning electron microscopy (SEM) and atomic force microscopy (AFM). The selectivity of aptasensor was tested in the presence of numerous proteins; protein C, thrombin, bovine serum albumin, factor Va and chromogenic substrate in different buffer mediums. The APC detection in the artificial serum; fetal bovine serum (FBS) was also performed impedimetrically. This dendrimer modified aptasensor technology brings several advantages: being single-use, fast screening with low-cost per measurement and resulting in sensitive detection of APC with the detection limits of 0.74 μg/mL (0.46 pmol in 35 μL sample) in buffer medium, and 2.03 μg/mL (1.27 pmol in 35 μL sample) in serum. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Numerical investigation of over expanded flow behavior in a single expansion ramp nozzle

    NASA Astrophysics Data System (ADS)

    Mousavi, Seyed Mahmood; Pourabidi, Reza; Goshtasbi-Rad, Ebrahim

    2018-05-01

    The single expansion ramp nozzle is severely over-expanded when the vehicle is at low speed, which hinders its ability to provide optimal configurations for combined cycle engines. The over-expansion leads to flow separation as a result of shock wave/boundary-layer interaction. Flow separation, and the presence of shocks themselves, result in a performance loss in the single expansion ramp nozzle, leading to reduced thrust and increased pressure losses. In the present work, the unsteady two dimensional compressible flow in an over expanded single expansion ramp nozzle has been investigated using finite volume code. To achieve this purpose, the Reynolds stress turbulence model and full multigrid initialization, in addition to the Smirnov's method for examining the errors accumulation, have been employed and the results are compared with available experimental data. The results show that the numerical code is capable of predicting the experimental data with high accuracy. Afterward, the effect of discontinuity jump in wall temperature as well as the length of straight ramp on flow behavior have been studied. It is concluded that variations in wall temperature and length of straight ramp change the shock wave boundary layer interaction, shock structure, shock strength as well as the distance between Lambda shocks.

  9. Coarse cross-bedded grainstones in a mid- to outer carbonate ramp, Bartonian of the Urbasa-Andia plateau (W Pyrenees, N Spain)

    NASA Astrophysics Data System (ADS)

    Baceta, José I.; Pomar, Luis; Mateu-Vicens, Guillem

    2017-04-01

    Most marine grainstones in carbonate ramps and platforms are commonly interpreted to form in high-energy, shallow-water settings where wave energy dissipates by friction on the sea floor. The locus of energy dissipation varies with platform type. On rimmed shelves, skeletal-oolitic sands mainly accumulate near the wave-agitated shelf margin as a rim, which restricts wave action and a low-energy lagoon may form landwards. On ramps and open platforms, by contrast, grainstones commonly accumulate in the shallower zone near or attached to the shoreline, grading basinward into muddier carbonate successions. Within this conceptual scheme, most carbonate ramp subdivisions have been established according to the facies and sedimentary structures associated to the bathymetry-related hydraulic regime, in which the bases of the surface storm-waves and the fairweather waves are the boundary layers. Since seagrasses encroached the oceans by the late Cretaceous, baffling the surface wave energy, and burrowing activity increased significantly, most Cenozoic ramp successions lack the bathymetry-related sedimentary structures and the record of wave and storm activity is commonly lost. This has induced ramp subdivision to become progressively based in light penetration, as inferred from the light dependence of the carbonate producers, particularly for the Cenozoic. This new scenario has permitted to recognize grainstone units detached from shoreline and shoals and produced at depths near the limit of light penetration, or even below, in basinal settings. Here we document a 90-100-m thick Eocene example of crossbedded skeletal grainstones composed by echinoderm-, bryozoan-, red-algal fragments and orthophragminid larger benthic foraminifers. This facies belt occurs at 20-km from the paleo-coastline, downdip of Nummulites-Discocyclina facies, and passes basinward into finely comminuted skeletal debris and marls with planktonic foraminifers of the outer ramp. The skeletal composition of

  10. Field test of coordinated ramp metering (CRM).

    DOT National Transportation Integrated Search

    2017-03-15

    This project has focused on field implementation and testing of a Coordinated Ramp Metering (CRM) algorithm at California State Route 99 : Northbound corridor in Sacramento between Calvine Road and the SR50 interchange after 12th Ave. It is a 9 mile ...

  11. Comparison of Zirconium Phosphonate-Modified Surfaces for Immobilizing Phosphopeptides and Phosphate-Tagged Proteins.

    PubMed

    Forato, Florian; Liu, Hao; Benoit, Roland; Fayon, Franck; Charlier, Cathy; Fateh, Amina; Defontaine, Alain; Tellier, Charles; Talham, Daniel R; Queffélec, Clémence; Bujoli, Bruno

    2016-06-07

    Different routes for preparing zirconium phosphonate-modified surfaces for immobilizing biomolecular probes are compared. Two chemical-modification approaches were explored to form self-assembled monolayers on commercially available primary amine-functionalized slides, and the resulting surfaces were compared to well-characterized zirconium phosphonate monolayer-modified supports prepared using Langmuir-Blodgett methods. When using POCl3 as the amine phosphorylating agent followed by treatment with zirconyl chloride, the result was not a zirconium-phosphonate monolayer, as commonly assumed in the literature, but rather the process gives adsorbed zirconium oxide/hydroxide species and to a lower extent adsorbed zirconium phosphate and/or phosphonate. Reactions giving rise to these products were modeled in homogeneous-phase studies. Nevertheless, each of the three modified surfaces effectively immobilized phosphopeptides and phosphopeptide tags fused to an affinity protein. Unexpectedly, the zirconium oxide/hydroxide modified surface, formed by treating the amine-coated slides with POCl3/Zr(4+), afforded better immobilization of the peptides and proteins and efficient capture of their targets.

  12. Probabilistic Wind Power Ramp Forecasting Based on a Scenario Generation Method

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

    Wang, Qin; Florita, Anthony R; Krishnan, Venkat K

    Wind power ramps (WPRs) are particularly important in the management and dispatch of wind power and currently drawing the attention of balancing authorities. With the aim to reduce the impact of WPRs for power system operations, this paper develops a probabilistic ramp forecasting method based on a large number of simulated scenarios. An ensemble machine learning technique is first adopted to forecast the basic wind power forecasting scenario and calculate the historical forecasting errors. A continuous Gaussian mixture model (GMM) is used to fit the probability distribution function (PDF) of forecasting errors. The cumulative distribution function (CDF) is analytically deduced.more » The inverse transform method based on Monte Carlo sampling and the CDF is used to generate a massive number of forecasting error scenarios. An optimized swinging door algorithm is adopted to extract all the WPRs from the complete set of wind power forecasting scenarios. The probabilistic forecasting results of ramp duration and start-time are generated based on all scenarios. Numerical simulations on publicly available wind power data show that within a predefined tolerance level, the developed probabilistic wind power ramp forecasting method is able to predict WPRs with a high level of sharpness and accuracy.« less

  13. Ramped-Amplitude Cross Polarization in Magic-Angle-Spinning NMR

    NASA Astrophysics Data System (ADS)

    Metz, G.; Wu, X. L.; Smith, S. O.

    The Hartmann-Hahn matching profile in CP-MAS NMR shows a strong mismatch dependence if the MAS frequency is on the order of the dipolar couplings in the sample. Under these conditions, the profile breaks down into a series of narrow matching bands separated by the spinning speed, and it becomes difficult to establish and maintain an efficient matching condition. Variable-amplitude CP (VACP), as introduced previously (Peersen et al., J. Magn. Reson. A104, 334, 1993), has been proven to be effective for restoring flat profiles at high spinning speeds. Here, a refined implementation of VACP using a ramped-amplitude cross-polarization sequence (RAMP-CP) is described. The order of the amplitude modulation is shown to be of importance for the cross-polarization process. The new pulse sequence with a linear amplitude ramp is not only easier to set up but also improves the performance of the variable-amplitude experiment in that it produces flat profiles over a wider range of matching conditions even with short total contact times. An increase in signal intensity is obtained compared to both con ventional CP and the originally proposed VACP sequence.

  14. Antimicrobial activity of biodegradable polysaccharide and protein-based films containing active agents.

    PubMed

    Kuorwel, Kuorwel K; Cran, Marlene J; Sonneveld, Kees; Miltz, Joseph; Bigger, Stephen W

    2011-04-01

    Significant interest has emerged in the introduction of food packaging materials manufactured from biodegradable polymers that have the potential to reduce the environmental impacts associated with conventional packaging materials. Current technologies in active packaging enable effective antimicrobial (AM) packaging films to be prepared from biodegradable materials that have been modified and/or blended with different compatible materials and/or plasticisers. A wide range of AM films prepared from modified biodegradable materials have the potential to be used for packaging of various food products. This review examines biodegradable polymers derived from polysaccharides and protein-based materials for their potential use in packaging systems designed for the protection of food products from microbial contamination. A comprehensive table that systematically analyses and categorizes much of the current literature in this area is included in the review.

  15. Expression and Activation of Horseradish Peroxidase-Protein A/G Fusion Protein in Silkworm Larvae for Diagnostic Purposes.

    PubMed

    Xxxx, Patmawati; Minamihata, Kosuke; Tatsuke, Tsuneyuki; Lee, Jae Man; Kusakabe, Takahiro; Kamiya, Noriho

    2018-06-01

    Recombinant protein production can create artificial proteins with desired functions by introducing genetic modifications to the target proteins. Horseradish peroxidase (HRP) has been used extensively as a reporter enzyme in biotechnological applications; however, recombinant production of HRP has not been very successful, hampering the utilization of HRP with genetic modifications. A fusion protein comprising an antibody binding protein and HRP will be an ideal bio-probe for high-quality HRP-based diagnostic systems. A HRP-protein A/G fusion protein (HRP-pAG) is designed and its production in silkworm (Bombyx mori) is evaluated for the first time. HRP-pAG is expressed in a soluble apo form, and is activated successfully by incubating with hemin. The activated HRP-pAG is used directly for ELISA experiments and retains its activity over 20 days at 4 °C. Moreover, HRP-pAG is modified with biotin by the microbial transglutaminase (MTG) reaction. The biotinylated HRP-pAG is conjugated with streptavidin to form a HRP-pAG multimer and the multimeric HRP-pAG produced higher signals in the ELISA system than monomeric HRP-pAG. The successful production of recombinant HRP in silkworm will contribute to creating novel HRP-based bioconjugates as well as further functionalization of HRP by applying enzymatic post-translational modifications. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Combining an Optical Resonance Biosensor with Enzyme Activity Kinetics to Understand Protein Adsorption and Denaturation

    PubMed Central

    Wilson, Kerry A.; Finch, Craig A.; Anderson, Phillip; Vollmer, Frank; Hickman, James J.

    2014-01-01

    Understanding protein adsorption and resultant conformation changes on modified and unmodified silicon dioxide surfaces is a subject of keen interest in biosensors, microfluidic systems and for medical diagnostics. However, it has been proven difficult to investigate the kinetics of the adsorption process on these surfaces as well as understand the topic of the denaturation of proteins and its effect on enzyme activity. A highly sensitive optical whispering gallery mode (WGM) resonator was used to study a catalytic enzyme’s adsorption processes on different silane modified glass substrates (plain glass control, DETA, 13F, and SiPEG). The WGM sensor was able to obtain high resolution kinetic data of glucose oxidase (GO) adsorption with sensitivity of adsorption better than that possible with SPR. The kinetic data, in combination with a functional assay of the enzyme activity, was used to test hypotheses on adsorption mechanisms. By fitting numerical models to the WGM sensograms for protein adsorption, and by confirming numerical predictions of enzyme activity in a separate assay, we were able to identify mechanisms for GO adsorption on different alkylsilanes and infer information about the adsorption of protein on nanostructured surfaces. PMID:25453976

  17. Combining an optical resonance biosensor with enzyme activity kinetics to understand protein adsorption and denaturation.

    PubMed

    Wilson, Kerry A; Finch, Craig A; Anderson, Phillip; Vollmer, Frank; Hickman, James J

    2015-01-01

    Understanding protein adsorption and resultant conformation changes on modified and unmodified silicon dioxide surfaces is a subject of keen interest in biosensors, microfluidic systems and for medical diagnostics. However, it has been proven difficult to investigate the kinetics of the adsorption process on these surfaces as well as understand the topic of the denaturation of proteins and its effect on enzyme activity. A highly sensitive optical whispering gallery mode (WGM) resonator was used to study a catalytic enzyme's adsorption processes on different silane modified glass substrates (plain glass control, DETA, 13 F, and SiPEG). The WGM sensor was able to obtain high resolution kinetic data of glucose oxidase (GO) adsorption with sensitivity of adsorption better than that possible with SPR. The kinetic data, in combination with a functional assay of the enzyme activity, was used to test hypotheses on adsorption mechanisms. By fitting numerical models to the WGM sensograms for protein adsorption, and by confirming numerical predictions of enzyme activity in a separate assay, we were able to identify mechanisms for GO adsorption on different alkylsilanes and infer information about the adsorption of protein on nanostructured surfaces. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Effect of Phthalic Anhydride Modified Soy Protein on Viscoelastic Properties of Polymer Composites

    USDA-ARS?s Scientific Manuscript database

    Phthalic anhydride (PA) modified soy protein isolates (SPI), both hydrolyzed and un-hydrolyzed, are investigated as reinforcement fillers in styrene-butadiene (SB) composites. The modification of SPI by PA increases the number of carboxylic acid functional groups on the protein surface and therefor...

  19. Chitinase modifying proteins from phylogenetically distinct lineages of Brassica pathogens

    USDA-ARS?s Scientific Manuscript database

    Chitinase modifying proteins (CMPs) are secreted fungal proteases that truncate specific plant class IV chitinases by cleaving peptide bonds in their amino termini. We recently identified a CMP from the Zea mays (maize) pathogen Fusarium verticillioides and found that it is a member of the fungalysi...

  20. Modification of recombinant maize ChitA chitinase by fungal chitinase-modifying proteins

    USDA-ARS?s Scientific Manuscript database

    In commercial maize, there are at least two different alleles of the chiA gene that encode alloforms of ChitA chitinase, a protein that is abundant in developing seed. Both known alloforms are modified by Bz-cmp, a protein secreted by the fungal pathogen Bipolaris zeicola. One alloform (ChitA-B73) i...

  1. Closed-loop separation control over a sharp edge ramp using genetic programming

    NASA Astrophysics Data System (ADS)

    Debien, Antoine; von Krbek, Kai A. F. F.; Mazellier, Nicolas; Duriez, Thomas; Cordier, Laurent; Noack, Bernd R.; Abel, Markus W.; Kourta, Azeddine

    2016-03-01

    We experimentally perform open and closed-loop control of a separating turbulent boundary layer downstream from a sharp edge ramp. The turbulent boundary layer just above the separation point has a Reynolds number Re_{θ }≈ 3500 based on momentum thickness. The goal of the control is to mitigate separation and early re-attachment. The forcing employs a spanwise array of active vortex generators. The flow state is monitored with skin-friction sensors downstream of the actuators. The feedback control law is obtained using model-free genetic programming control (GPC) (Gautier et al. in J Fluid Mech 770:442-457, 2015). The resulting flow is assessed using the momentum coefficient, pressure distribution and skin friction over the ramp and stereo PIV. The PIV yields vector field statistics, e.g. shear layer growth, the back-flow area and vortex region. GPC is benchmarked against the best periodic forcing. While open-loop control achieves separation reduction by locking-on the shedding mode, GPC gives rise to similar benefits by accelerating the shear layer growth. Moreover, GPC uses less actuation energy.

  2. Heterologous Protein Secretion in Lactobacilli with Modified pSIP Vectors

    PubMed Central

    Karlskås, Ingrid Lea; Maudal, Kristina; Axelsson, Lars; Rud, Ida; Eijsink, Vincent G. H.; Mathiesen, Geir

    2014-01-01

    We describe new variants of the modular pSIP-vectors for inducible gene expression and protein secretion in lactobacilli. The basic functionality of the pSIP system was tested in Lactobacillus strains representing 14 species using pSIP411, which harbors the broad-host-range Lactococcus lactis SH71rep replicon and a β-glucuronidase encoding reporter gene. In 10 species, the inducible gene expression system was functional. Based on these results, three pSIP vectors with different signal peptides were modified by replacing their narrow-host-range L. plantarum 256rep replicon with SH71rep and transformed into strains of five different species of Lactobacillus. All recombinant strains secreted the target protein NucA, albeit with varying production levels and secretion efficiencies. The Lp_3050 derived signal peptide generally resulted in the highest levels of secreted NucA. These modified pSIP vectors are useful tools for engineering a wide variety of Lactobacillus species. PMID:24614815

  3. ALINEA local ramp metering : summary of field results

    DOT National Transportation Integrated Search

    1997-01-01

    Asservissement Linaire dEntre Autoroutire (ALINEA), a local feedback ramp-metering strategy, has had multiple field applications, and more applications are planned in several European countries. The main features of ALINEA are presented and ...

  4. The interrelationship between muscle oxygenation, muscle activation, and pulmonary oxygen uptake to incremental ramp exercise: influence of aerobic fitness.

    PubMed

    Boone, Jan; Barstow, Thomas J; Celie, Bert; Prieur, Fabrice; Bourgois, Jan

    2016-01-01

    We investigated whether muscle and ventilatory responses to incremental ramp exercise would be influenced by aerobic fitness status by means of a cross-sectional study with a large subject population. Sixty-four male students (age: 21.2 ± 3.2 years) with a heterogeneous peak oxygen uptake (51.9 ± 6.3 mL·min(-1)·kg(-1), range 39.7-66.2 mL·min(-1)·kg(-1)) performed an incremental ramp cycle test (20-35 W·min(-1)) to exhaustion. Breath-by-breath gas exchange was recorded, and muscle activation and oxygenation were measured with surface electromyography and near-infrared spectroscopy, respectively. The integrated electromyography (iEMG), mean power frequency (MPF), deoxygenated [hemoglobin and myoglobin] (deoxy[Hb+Mb]), and total[Hb+Mb] responses were set out as functions of work rate and fitted with a double linear function. The respiratory compensation point (RCP) was compared and correlated with the breakpoints (BPs) (as percentage of peak oxygen uptake) in muscle activation and oxygenation. The BP in total[Hb+Mb] (83.2% ± 3.0% peak oxygen uptake) preceded (P < 0.001) the BP in iEMG (86.7% ± 4.0% peak oxygen uptake) and MPF (86.3% ± 4.1% peak oxygen uptake), which in turn preceded (P < 0.01) the BP in deoxy[Hb+Mb] (88.2% ± 4.5% peak oxygen uptake) and RCP (87.4% ± 4.5% peak oxygen uptake). Furthermore, the peak oxygen uptake was significantly (P < 0.001) positively correlated to the BPs and RCP, indicating that the BPs in total[Hb+Mb] (r = 0.66; P < 0.001), deoxy[Hb+Mb] (r = 0.76; P < 0.001), iEMG (r = 0.61; P < 0.001), MPF (r = 0.63; P < 0.001), and RCP (r = 0.75; P < 0.001) occurred at a higher percentage of peak oxygen uptake in subjects with a higher peak oxygen uptake. In this study a close relationship between muscle oxygenation, activation, and pulmonary oxygen uptake was found, occurring in a cascade of events. In subjects with a higher aerobic fitness level this cascade occurred at a higher relative intensity.

  5. Hot-spot analysis to dissect the functional protein-protein interface of a tRNA-modifying enzyme.

    PubMed

    Jakobi, Stephan; Nguyen, Tran Xuan Phong; Debaene, François; Metz, Alexander; Sanglier-Cianférani, Sarah; Reuter, Klaus; Klebe, Gerhard

    2014-10-01

    Interference with protein-protein interactions of interfaces larger than 1500 Ų by small drug-like molecules is notoriously difficult, particularly if targeting homodimers. The tRNA modifying enzyme Tgt is only functionally active as a homodimer. Thus, blocking Tgt dimerization is a promising strategy for drug therapy as this protein is key to the development of Shigellosis. Our goal was to identify hot-spot residues which, upon mutation, result in a predominantly monomeric state of Tgt. The detailed understanding of the spatial location and stability contribution of the individual interaction hot-spot residues and the plasticity of motifs involved in the interface formation is a crucial prerequisite for the rational identification of drug-like inhibitors addressing the respective dimerization interface. Using computational analyses, we identified hot-spot residues that contribute particularly to dimer stability: a cluster of hydrophobic and aromatic residues as well as several salt bridges. This in silico prediction led to the identification of a promising double mutant, which was validated experimentally. Native nano-ESI mass spectrometry showed that the dimerization of the suggested mutant is largely prevented resulting in a predominantly monomeric state. Crystal structure analysis and enzyme kinetics of the mutant variant further support the evidence for enhanced monomerization and provide first insights into the structural consequences of the dimer destabilization. © 2014 Wiley Periodicals, Inc.

  6. WALK UP RAMP - ASTRONAUT THOMAS P. STAFFORD - MISC.

    NASA Image and Video Library

    1966-06-03

    S66-32149 (3 June 1966) --- Astronauts Thomas P. Stafford (foreground), command pilot, and Eugene A. Cernan, pilot, walk up the ramp at Pad 19 during the Gemini-9A prelaunch countdown. Photo credit: NASA

  7. Gap Detection in School-Age Children and Adults: Center Frequency and Ramp Duration

    PubMed Central

    Porter, Heather L.; Hall, Joseph W.; Grose, John H.

    2017-01-01

    Purpose The age at which gap detection becomes adultlike differs, depending on the stimulus characteristics. The present study evaluated whether the developmental trajectory differs as a function of stimulus frequency region or duration of the onset and offset ramps bounding the gap. Method Thresholds were obtained for wideband noise (500–4500 Hz) with 4- or 40-ms raised-cosine ramps and for a 25-Hz-wide low-fluctuation narrowband noise centered on either 500 or 5000 Hz with 40-ms ramps. Stimuli were played continuously at 70 dB SPL, and the task was to indicate which of 3 intervals contained a gap. Listeners were 5.2- to 15.1-year-old children (n = 40) and adults (n = 10) with normal hearing. Results Regardless of listener age, gap detection thresholds for the wideband noise tended to be lower when gaps were shaped using 4-ms rather than 40-ms ramps. Thresholds also tended to be lower for the low-fluctuation narrowband noise centered on 5000 Hz than 500 Hz. Performance reached adult levels after 11 years of age for all 4 stimuli. Maturation was not uniform across individuals, however; a subset of young children performed like adults, including some 5-year-olds. Conclusion For these stimuli, the developmental trajectory was similar regardless of narrowband noise center frequency or wideband noise onset and offset ramp duration. PMID:28056469

  8. The impact of CRISPR repeat sequence on structures of a Cas6 protein-RNA complex

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

    Wang, Ruiying; Zheng, Han; Preamplume, Gan

    The repeat-associated mysterious proteins (RAMPs) comprise the most abundant family of proteins involved in prokaryotic immunity against invading genetic elements conferred by the clustered regularly interspaced short palindromic repeat (CRISPR) system. Cas6 is one of the first characterized RAMP proteins and is a key enzyme required for CRISPR RNA maturation. Despite a strong structural homology with other RAMP proteins that bind hairpin RNA, Cas6 distinctly recognizes single-stranded RNA. Previous structural and biochemical studies show that Cas6 captures the 5' end while cleaving the 3' end of the CRISPR RNA. Here, we describe three structures and complementary biochemical analysis of amore » noncatalytic Cas6 homolog from Pyrococcus horikoshii bound to CRISPR repeat RNA of different sequences. Our study confirms the specificity of the Cas6 protein for single-stranded RNA and further reveals the importance of the bases at Positions 5-7 in Cas6-RNA interactions. Substitutions of these bases result in structural changes in the protein-RNA complex including its oligomerization state.« less

  9. Effect of ramp configuration on easiness of handling, heart rate, and behavior of near-market weight pigs at unloading.

    PubMed

    Goumon, S; Faucitano, L; Bergeron, R; Crowe, T; Connor, M L; Gonyou, H W

    2013-08-01

    Three experiments, each using 280 pigs, were conducted in a simulated compartment to test the effect of angle of entrance (AOE) to the ramp (90°, 60°, 30°, or 0°), ramp slope (0°, 16°, 21°, or 26°), and an initial 20-cm step associated with 16° or 21° ramp slopes on the ease of handling, heart rate (HR), and behavior of near market-weight pigs during unloading. Heart rate (pigs and handler), unloading time, interventions of the handler, and reactions of the pigs were monitored. The results of the first experiment show that using a 90° AOE had detrimental effects on ease of handling (P < 0.05), HR of the pig (P < 0.05), and behavior (P < 0.05). The 0° and 30° AOE appeared to improve the ease of unloading, whereas the 60° AOE had an intermediate effect. The 30° AOE appeared to be preferable, because pigs moved at this angle balked less frequently (P < 0.01) and required less manipulation (P < 0.05) than pigs moved with a 0° AOE. The results of the second experiment show that the use of a flat ramp led to the easiest unloading, as demonstrated by the lower number of balks (P < 0.001) when pigs were moved to the ramp and less frequent use of paddle (P = 0.001) or voice (P < 0.001) on the ramp, compared with the other treatments. However, the flat ramp did not differ from the 21° ramp in many of the variables reflecting ease of handling, which may be explained by the difference in configuration between the ramps. The results also show that the use of the steepest ramp slope had the most detrimental effect on balking and backing up behavior of pigs (P < 0.001), and handling (touches, slaps, and pushes; P < 0.05 for all) when moved to the ramp and on unloading time (P < 0.01). No differences in pig HR (P < 0.05) and ease of handling on the ramp (P < 0.05) were found between a 26° and 16° ramp slope, suggesting that the length of the ramp may be one of the factors that make unloading more difficult. The results of the last experiment show that an initial

  10. Off-ramps and on-ramps: keeping talented women on the road to success.

    PubMed

    Hewlett, Sylvia Ann; Luce, Carolyn Buck

    2005-03-01

    Most professional women step off the career fast track at some point. With children to raise, elderly parents to care for, and other pulls on their time, these women are confronted with one off-ramp after another. When they feel pushed at the same time by long hours and unsatisfying work, the decision to leave becomes even easier. But woe to the woman who intends for that exit to be temporary. The on-ramps for professional women to get back on track are few and far between, the authors confirm. Their new survey research reveals for the first time the extent of the problem--what percentage of highly qualified women leave work and for how long, what obstacles they face coming back, and what price they pay for their time-outs. And what are the implications for corporate America? One thing at least seems clear: As market and economic factors align in ways guaranteed to make talent constraints and skill shortages huge issues again, employers must learn to reverse this brain drain. Like it or not, large numbers of highly qualified, committed women need to take time out of the workplace. The trick is to help them maintain connections that will allow them to reenter the workforce without being marginalized for the rest of their lives. Strategies for building such connections include creating reduced-hour jobs, providing flexibility in the workday and in the arc of a career, removing the stigma of taking time off, refusing to burn bridges, offering outlets for altruism, and nurturing women's ambition.

  11. Micro-Ramp Flow Control for Oblique Shock Interactions: Comparisons of Computational and Experimental Data

    NASA Technical Reports Server (NTRS)

    Hirt, Stefanie M.; Reich, David B.; O'Connor, Michael B.

    2010-01-01

    Computational fluid dynamics was used to study the effectiveness of micro-ramp vortex generators to control oblique shock boundary layer interactions. Simulations were based on experiments previously conducted in the 15 x 15 cm supersonic wind tunnel at NASA Glenn Research Center. Four micro-ramp geometries were tested at Mach 2.0 varying the height, chord length, and spanwise spacing between micro-ramps. The overall flow field was examined. Additionally, key parameters such as boundary-layer displacement thickness, momentum thickness and incompressible shape factor were also examined. The computational results predicted the effects of the micro-ramps well, including the trends for the impact that the devices had on the shock boundary layer interaction. However, computing the shock boundary layer interaction itself proved to be problematic since the calculations predicted more pronounced adverse effects on the boundary layer due to the shock than were seen in the experiment.

  12. A high-throughput, modified ALS activity assay for Cyperus difformis and Schoenoplectus mucronatus seedlings.

    PubMed

    Pedroso, Rafael M; Al-Khatib, Kassim; Hanson, Bradley D; Fischer, Albert J

    2017-01-01

    Cyperus difformis L. (CYPDI) and Schoenoplectus mucronatus (L.) Palla (SCHMU) are major weeds of California (CA) rice, where resistance to acetolactate synthase (ALS)-inhibitors was identified in several CYPDI and SCHMU populations that have also evolved resistance to photosystem II (PSII)-inhibiting herbicides. The mechanism of ALS resistance in these populations remains to be clarified but this information is crucial in a weed management program, especially in a scenario where resistance to multiple herbicides has been identified. ALS activity assays are commonly used to diagnose resistance to ALS-inhibitors, but protocols currently available are burdensome for the study of CYPDI and SCHMU, as they require large amounts of plant material from young seedlings and have low yields. Our objective was to investigate the ALS resistance mechanism in suspected ALS-resistant (R) CYPDI and SCHMU biotypes using a modified ALS activity assay that requires less plant material. ALS enzymes from suspected R biotypes were at least 10,000-fold less sensitive to bensulfuron-methyl than susceptible (S) cohorts, indicating ALS resistance that is likely due to an altered target-site. Protein concentration (mgg -1 tissue) did not differ between R and S biotypes within each species, suggesting that R biotypes do not over produce ALS enzymes. CYPDI biotypes had up to 4-fold more protein per mg of tissue than SCHMU biotypes, but up to 7-fold more acetoin per mg -1 protein was quantified in SCHMU, suggesting greater ALS catalytic ability in SCHMU biotypes, regardless of their herbicide resistance status. Our optimized protocol to measure ALS activity allowed for up to a 3-fold increase in the number of assays performed per g of leaf tissue. The modified assay may be useful for measuring ALS activity in other weed species that also produce small amount of foliage in early growth stages when protein in tissue is most abundant. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Preparation of Modified Films with Protein from Grouper Fish

    PubMed Central

    Tecante, A.; Granados-Navarrete, S.; Martínez-García, C.

    2016-01-01

    A protein concentrate (PC) was obtained from Grouper fish skin and it was used to prepare films with different amounts of sorbitol and glycerol as plasticizers. The best performing films regarding resistance were then modified with various concentrations of CaCl2, CaSO4 (calcium salts), and glucono-δ-lactone (GDL) with the purpose of improving their mechanical and barrier properties. These films were characterized by determining their mechanical properties and permeability to water vapor and oxygen. Formulations with 5% (w/v) protein and 75% sorbitol and 4% (w/v) protein with a mixture of 15% glycerol and 15% sorbitol produced adequate films. Calcium salts and GDL increased the tensile fracture stress but reduced the fracture strain and decreased water vapor permeability compared with control films. The films prepared represent an attractive alternative for being used as food packaging materials. PMID:27597950

  14. Interactions of proteins in human plasma with modified polystyrene resins.

    PubMed

    Boisson-Vidal, C; Jozefonvicz, J; Brash, J L

    1991-01-01

    Investigations are reported on the composition of protein layers adsorbed from plasma to various modified polystyrene resins. As well as polystyrene itself, polystyrene bearing sulfonate groups in the benzene rings, and polystyrene sulfonate in which the sulfonate groups were converted to amino acid sulfamide, were investigated. Some of these resins were shown in previous work to have anticoagulant properties. To study the adsorption of proteins from plasma, the resins were exposed to citrate anticoagulated human plasma for 3 h. Adsorbed proteins were then eluted sequentially by 1M Tris buffer and 4% SDS solution, and examined by SDS-PAGE. The gel patterns were similar on all resins except polystyrene. From the MWs of the gel bands, the major protein component appeared to be fibrinogen. Smaller amounts of plasminogen, transferrin, albumin, and IgG were also present. In addition, Ouchterlony immunoassay of the eluates from one resin gave positive identification of complement C3, fibronectin, IgG, and IgM. Many other minor gel bands remain unidentified. A consistent finding for all resins was the presence of plasmin-type fibrinogen degradation products though the amounts varied with resin type. It is concluded from this (and from experiments showing FDP formation when fibrinogen was absorbed to the resins, from buffer containing a trace of plasminogen) that the functional groups in these materials promote the adsorption of plasminogen and its activation to a plasmin-like molecule. It appears from the substantial quantities of fibrinogen adsorbed to these materials after 3 h exposure to plasma that the Vroman effect (giving transient adsorption of fibrinogen) is not operative on these materials. It is hypothesized that specific interactions occur between fibrinogen and sulfonate groups.

  15. Dolomitization on an evaporitic Paleoproterozoic ramp: Widespread synsedimentary dolomite in the Denault Formation, Labrador Trough, Canada

    NASA Astrophysics Data System (ADS)

    Zentmyer, R. A.; Pufahl, P. K.; James, N. P.; Hiatt, E. E.

    2011-06-01

    The Denault Formation (2.1-1.9 Ga) crops out in the Labrador Trough, northeastern Québec and western Labrador. Rocks surrounding the town of Schefferville, Quebec contain textural characteristics consistent with deposition on the middle and outer portions of a storm-influenced shallow ramp. Mid-ramp facies consist of intraclastic grainstones with hummocky cross-stratification (HCS), swaley cross-stratification (SCS), current ripples, and graded event beds. Further outboard, grainstones grade into deeper-water laminites that are composed of even, mm-scale couplets of flat-lying organic and dolomudstone laminae. Scours within the laminites suggest periodic storm activity. Laminites gradually grade into outer ramp deep-water shales. An isolated eastern stromatolitic buildup is separated from these ramp facies by 50 km (present day). This succession can be interpreted as the remnant of a near-continuous margin or may simply represent an isolated accumulation that developed on a pre-existing topographic high. The presence of gypsum pseudomorphs in all lithofacies indicates that the Denault margin was restricted and evaporitic. Four paragenetic stages are recognized in the diagenetic evolution of the Denault Formation: (1) carbonate deposition, contemporaneous marine cementation, authigenic gypsum growth, and precipitation of authigenic chert; (2) synsedimentary mimetic dolomite precipitation; (3) pore-rimming and pore-occluding shallow burial dolomite cement; and (4) fabric destructive, sutured, anhedral burial dolomite. Gypsum crystals occur in all lithofacies, form the nuclei of interstitial dolomite rhombs, average 10 μm in length, and often display swallowtail twinning. Paleoproterozoic ocean water had very low concentrations of dissolved sulfate and evaporation in restricted settings would have been required to form gypsum. Formation of microcrystalline gypsum across this restricted ramp facilitated dolomite precipitation by increasing pore water Mg/Ca ratios and

  16. Correlating In Vitro Splice Switching Activity With Systemic In Vivo Delivery Using Novel ZEN-modified Oligonucleotides.

    PubMed

    Hammond, Suzan M; McClorey, Graham; Nordin, Joel Z; Godfrey, Caroline; Stenler, Sofia; Lennox, Kim A; Smith, C I Edvard; Jacobi, Ashley M; Varela, Miguel A; Lee, Yi; Behlke, Mark A; Wood, Matthew J A; Andaloussi, Samir E L

    2014-11-25

    Splice switching oligonucleotides (SSOs) induce alternative splicing of pre-mRNA and typically employ chemical modifications to increase nuclease resistance and binding affinity to target pre-mRNA. Here we describe a new SSO non-base modifier (a naphthyl-azo group, "ZEN™") to direct exon exclusion in mutant dystrophin pre-mRNA to generate functional dystrophin protein. The ZEN modifier is placed near the ends of a 2'-O-methyl (2'OMe) oligonucleotide, increasing melting temperature and potency over unmodified 2'OMe oligonucleotides. In cultured H2K cells, a ZEN-modified 2'OMe phosphorothioate (PS) oligonucleotide delivered by lipid transfection greatly enhanced dystrophin exon skipping over the same 2'OMePS SSO lacking ZEN. However, when tested using free gymnotic uptake in vitro and following systemic delivery in vivo in dystrophin deficient mdx mice, the same ZEN-modified SSO failed to enhance potency. Importantly, we show for the first time that in vivo activity of anionic SSOs is modelled in vitro only when using gymnotic delivery. ZEN is thus a novel modifier that enhances activity of SSOs in vitro but will require improved delivery methods before its in vivo clinical potential can be realized.

  17. [Pathogenic activity modulation of Escherichia coli TL+ toxin with an isolated protein of Giardia intestinalis and a synthetic peptide].

    PubMed

    Jiménez-Cardoso, E; Eligio-García, L; Jiménez-Cardoso, J M; Angeles-Anguiano, E; Tobilla-Mercado, J M; Castañeda, G

    2001-01-01

    It is know that a protein from Giardia intestinalis works as a substrate for V. cholerae and Escherichia coli. The toxic activity of both activates protein G form intestinal mucosa with a pathogenic activity results. In the present study, the pathogenic activity of subunit A of Vibrio cholerae toxin (ADP-ribosyltranferase) using isolated fragments from: Giardia intestinalis and a synthetic peptide were used as modulators in vivo. Adult Neo Zealand males rabbits with ileal loop were prepared and different mixtures of heat labile enterotoxin obtained from Escherichia coli H10407 and ARF protein isolated by electrofocusing from Giardia intestinalis Portland I were inoculated in the loops. The toxin activity was evaluated by luminal liquid secretion and cyclic AMP concentration in tissues (each loop). ADP ribosyltranferase activity was modulated, due to a decreased of luminal secretion and cAMP in tissues. Such results were seen when synthetic peptide and subunit A from Vibrio cholerae were used. The ADP ribosyltranferase activity of heat labile Escherichia coli and Vibrio cholerae toxins were modified by in vitro and in vivo interaction with ARF protein, which modified pathogenic effect over rabbits intestinal epithelium.

  18. Three-dimensional supersonic flow around double compression ramp with finite span

    NASA Astrophysics Data System (ADS)

    Lee, H. S.; Lee, J. H.; Park, G.; Park, S. H.; Byun, Y. H.

    2017-01-01

    Three-dimensional flows of Mach number 3 around a double-compression ramp with finite span have been investigated numerically. Shadowgraph visualisation images obtained in a supersonic wind tunnel are used for comparison. A three-dimensional Reynolds-averaged Navier-Stokes solver was used to obtain steady numerical solutions. Two-dimensional numerical results are also compared. Four different cases were studied: two different second ramp angles of 30° and 45° in configurations with and without sidewalls, respectively. Results showed that there is a leakage of mass and momentum fluxes heading outwards in the spanwise direction for three-dimensional cases without sidewalls. The leakage changed the flow characteristics of the shock-induced boundary layer and resulted in the discrepancy between the experimental data and two-dimensional numerical results. It is found that suppressing the flow leakage by attaching the sidewalls enhances the two-dimensionality of the experimental data for the double-compression ramp flow.

  19. The ability of laying pullets to negotiate two ramp designs as measured by bird preference and behaviour

    PubMed Central

    Weeks, Claire A.; Norman, Kate I.; Nicol, Christine J.

    2017-01-01

    Background Laying hens are often kept in barn or free-range systems where they must negotiate level changes in the house to access resources. However, collisions and resultant keel fractures are commonplace. Producers sometimes add ramps to make raised areas more accessible but designs vary and very little research has investigated bird preference or behaviour when using different ramp designs, or the effect of ramp design on falls and collisions. Methods Two ramp designs were studied in an experimental setting—a ramp made of plastic poultry slats (grid ramp, GR) and a ramp made of wooden rungs (ladder ramp, LR). Sixty-four young female hens were trained to move to a food reward and this was used to test their behavioural responses when first negotiating the two different ramps during individual tests. Both upward and downward transitions were studied. Ramp preference was also tested using a room that replicated a commercial single-tier system with both types of ramp available. Birds were placed in this room in groups of 16 for three days and their use of the ramps studied. Results A greater percentage of birds successfully completed (reached the reward bowl) on the GR than the LR during both upward (58% vs 37%) and downward (83% vs 73%) transitions, and a smaller percentage of birds made zero attempts to use the GR than the LR (upwards: 13% vs 56%, downwards: 8% vs 26%). When making a downward transition, more hesitation behaviours were seen (head orientations, stepping on the spot, moving away) for the LR. However, more head orientations were seen for the GR during the upward transition. Birds were more likely to abort attempts (an attempt began when a bird placed both feet on the ramp) to move up the GR than the LR. Birds took longer to negotiate the LR than the GR in both directions, and more pauses were seen during a successful upward transition on the LR. Birds were more likely to move down the GR by walking/running whereas birds tended to jump over the

  20. Application of Micro-ramp Flow Control Devices to an Oblique Shock Interaction

    NASA Technical Reports Server (NTRS)

    Hirt, Stefanie; Anderson, Bernhard

    2007-01-01

    Tests are planned in the 15cm x 15cm supersonic wind tunnel at NASA Glenn to demonstrate the applicability of micro-ramp flow control to the management of shock wave boundary layer interactions. These tests will be used as a database for computational fluid dynamics (CFD) validation and Design of Experiments (DoE) design information. Micro-ramps show potential for mechanically simple and fail-safe boundary layer control.

  1. Suitability of representative electrochemical energy storage technologies for ramp-rate control of photovoltaic power

    NASA Astrophysics Data System (ADS)

    Jiang, Yu; Fletcher, John; Burr, Patrick; Hall, Charles; Zheng, Bowen; Wang, Da-Wei; Ouyang, Zi; Lennon, Alison

    2018-04-01

    Photovoltaic (PV) systems can exhibit rapid variances in their power output due to irradiance changes which can destabilise an electricity grid. This paper presents a quantitative comparison of the suitability of different electrochemical energy storage system (ESS) technologies to provide ramp-rate control of power in PV systems. Our investigations show that, for PV systems ranging from residential rooftop systems to megawatt power systems, lithium-ion batteries with high energy densities (up to 600 Wh L-1) require the smallest power-normalised volumes to achieve the ramp rate limit of 10% min-1 with 100% compliance. As the system size increases, the ESS power-normalised volume requirements are significantly reduced due to aggregated power smoothing, with high power lithium-ion batteries becoming increasingly more favourable with increased PV system size. The possibility of module-level ramp-rate control is also introduced, and results show that achievement of a ramp rate of 10% min-1 with 100% compliance with typical junction box sizes will require ESS energy and power densities of 400 Wh L-1 and 2300 W L-1, respectively. While module-level ramp-rate control can reduce the impact of solar intermittence, the requirement is challenging, especially given the need for low cost and long cycle life.

  2. Fully non-inductive second harmonic electron cyclotron plasma ramp-up in the QUEST spherical tokamak

    NASA Astrophysics Data System (ADS)

    Idei, H.; Kariya, T.; Imai, T.; Mishra, K.; Onchi, T.; Watanabe, O.; Zushi, H.; Hanada, K.; Qian, J.; Ejiri, A.; Alam, M. M.; Nakamura, K.; Fujisawa, A.; Nagashima, Y.; Hasegawa, M.; Matsuoka, K.; Fukuyama, A.; Kubo, S.; Shimozuma, T.; Yoshikawa, M.; Sakamoto, M.; Kawasaki, S.; Nakashima, H.; Higashijima, A.; Ide, S.; Maekawa, T.; Takase, Y.; Toi, K.

    2017-12-01

    Fully non-inductive second (2nd) harmonic electron cyclotron (EC) plasma current ramp-up was demonstrated with a newlly developed 28 GHz system in the QUEST spherical tokamak. A high plasma current of 54 kA was non-inductively ramped up and sustained stably for 0.9 s with a 270 kW 28 GHz wave. A higher plasma current of 66 kA was also non-inductively achieved with a slow ramp-up of the vertical field. We have achieved a significantly higher plasma current than those achieved previously with the 2nd harmonic EC waves. This fully non-inductive 2nd harmonic EC plasma ramp-up method might be useful for future burning plasma devices and fusion reactors, in particular for operations at half magnetic field with the same EC heating equipment.

  3. JF-102A on ramp

    NASA Technical Reports Server (NTRS)

    1956-01-01

    Convair JF-102A (54-1374) on the ramp at NACA High-Speed Flight Station , Edwards, California in 1956. The most prominent new feature distinguishing the JF-102A from the YF-102 was a longer fuselage with a pinched or 'coke-bottle' waist. Note wing-fences on both wings. The JF-102A Characteristics are: Wing Span, ft. 38.1 Fuselage length, ft. 63.4 Vertical Tail height, ft. 21.2 Power Plant: Pratt & Whitney J57-P-23 turbojet

  4. TALE factors poise promoters for activation by Hox proteins.

    PubMed

    Choe, Seong-Kyu; Ladam, Franck; Sagerström, Charles G

    2014-01-27

    Hox proteins form complexes with TALE cofactors from the Pbx and Prep/Meis families to control transcription, but it remains unclear how Hox:TALE complexes function. Examining a Hoxb1b:TALE complex that regulates zebrafish hoxb1a transcription, we find maternally deposited TALE proteins at the hoxb1a promoter already during blastula stages. These TALE factors recruit histone-modifying enzymes to promote an active chromatin profile at the hoxb1a promoter and also recruit RNA polymerase II (RNAPII) and P-TEFb. However, in the presence of TALE factors, RNAPII remains phosphorylated on serine 5 and hoxb1a transcription is inefficient. By gastrula stages, Hoxb1b binds together with TALE factors to the hoxb1a promoter. This triggers P-TEFb-mediated transitioning of RNAPII to the serine 2-phosphorylated form and efficient hoxb1a transcription. We conclude that TALE factors access promoters during early embryogenesis to poise them for activation but that Hox proteins are required to trigger efficient transcription. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Sound exposure changes European seabass behaviour in a large outdoor floating pen: Effects of temporal structure and a ramp-up procedure.

    PubMed

    Neo, Y Y; Hubert, J; Bolle, L; Winter, H V; Ten Cate, C; Slabbekoorn, H

    2016-07-01

    Underwater sound from human activities may affect fish behaviour negatively and threaten the stability of fish stocks. However, some fundamental understanding is still lacking for adequate impact assessments and potential mitigation strategies. For example, little is known about the potential contribution of the temporal features of sound, the efficacy of ramp-up procedures, and the generalisability of results from indoor studies to the outdoors. Using a semi-natural set-up, we exposed European seabass in an outdoor pen to four treatments: 1) continuous sound, 2) intermittent sound with a regular repetition interval, 3) irregular repetition intervals and 4) a regular repetition interval with amplitude 'ramp-up'. Upon sound exposure, the fish increased swimming speed and depth, and swam away from the sound source. The behavioural readouts were generally consistent with earlier indoor experiments, but the changes and recovery were more variable and were not significantly influenced by sound intermittency and interval regularity. In addition, the 'ramp-up' procedure elicited immediate diving response, similar to the onset of treatment without a 'ramp-up', but the fish did not swim away from the sound source as expected. Our findings suggest that while sound impact studies outdoors increase ecological and behavioural validity, the inherently higher variability also reduces resolution that may be counteracted by increasing sample size or looking into different individual coping styles. Our results also question the efficacy of 'ramp-up' in deterring marine animals, which warrants more investigation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. CGRP Receptor Biology: Is There More Than One Receptor?

    PubMed

    Hay, Debbie L

    2018-05-25

    Calcitonin gene-related peptide (CGRP) has many reported pharmacological actions. Can a single receptor explain all of these? This chapter outlines the molecular nature of reported CGRP binding proteins and their pharmacology. Consideration of whether CGRP has only one or has more receptors is important because of the key role that this peptide plays in migraine. It is widely thought that the calcitonin receptor-like receptor together with receptor activity-modifying protein 1 (RAMP1) is the only relevant receptor for CGRP. However, some closely related receptors also have high affinity for CGRP and it is still plausible that these play a role in CGRP biology, and in migraine. The calcitonin receptor/RAMP1 complex, which is currently called the AMY 1 receptor, seems to be the most likely candidate but more investigation is needed to determine its role.

  7. Antioxidant activity and protein-polyphenol interactions in a pomegranate (Punica granatum L.) yogurt.

    PubMed

    Trigueros, Lorena; Wojdyło, Aneta; Sendra, Esther

    2014-07-09

    Pomegranate juice (PGJ) is rich in phenolics which are potent antioxidants but also prone to interact with proteins. A yogurt rich in PGJ (40%) made from arils was elaborated (PGY) to determine the antioxidant activity and to estimate the phenolics-proteins interaction during 28 days of cold storage. Juice, yogurts, and protein-free permeates were analyzed for phenolic composition. Yogurt fermentation modified the anthocyanin profile of the initial PGJ, especially the content in cyanidin-3-O-glucoside. During storage, individual anthocyanin content in PGY decreased but it did not modify yogurt color. The analysis of permeates revealed that the degree of phenol-protein interaction depends on the type of phenolic, ellagic acid and dephinidin-3,5-O-diglucoside being the least bound phenolic compounds. The presence of PGJ in yogurt enhanced radical scavenging performance, whereas all the observed ferric reducing power ability of PGY was strictly due to the PGJ present. The 84.73% of total anthocyanins remained bound to proteins at the first day of storage and 90.06% after 28 days of cold storage, revealing the high affinity of anthocyanins for milk proteins.

  8. Static internal performance of a single expansion ramp nozzle with multiaxis thrust vectoring capability

    NASA Technical Reports Server (NTRS)

    Capone, Francis J.; Schirmer, Alberto W.

    1993-01-01

    An investigation was conducted at static conditions in order to determine the internal performance characteristics of a multiaxis thrust vectoring single expansion ramp nozzle. Yaw vectoring was achieved by deflecting yaw flaps in the nozzle sidewall into the nozzle exhaust flow. In order to eliminate any physical interference between the variable angle yaw flap deflected into the exhaust flow and the nozzle upper ramp and lower flap which were deflected for pitch vectoring, the downstream corners of both the nozzle ramp and lower flap were cut off to allow for up to 30 deg of yaw vectoring. The effects of nozzle upper ramp and lower flap cutout, yaw flap hinge line location and hinge inclination angle, sidewall containment, geometric pitch vector angle, and geometric yaw vector angle were studied. This investigation was conducted in the static-test facility of the Langley 16-Foot Transonic Tunnel at nozzle pressure ratios up to 8.0.

  9. Amino acid signature enables proteins to recognize modified tRNA.

    PubMed

    Spears, Jessica L; Xiao, Xingqing; Hall, Carol K; Agris, Paul F

    2014-02-25

    Human tRNA(Lys3)UUU is the primer for HIV replication. The HIV-1 nucleocapsid protein, NCp7, facilitates htRNA(Lys3)UUU recruitment from the host cell by binding to and remodeling the tRNA structure. Human tRNA(Lys3)UUU is post-transcriptionally modified, but until recently, the importance of those modifications in tRNA recognition by NCp7 was unknown. Modifications such as the 5-methoxycarbonylmethyl-2-thiouridine at anticodon wobble position-34 and 2-methylthio-N(6)-threonylcarbamoyladenosine, adjacent to the anticodon at position-37, are important to the recognition of htRNA(Lys3)UUU by NCp7. Several short peptides selected from phage display libraries were found to also preferentially recognize these modifications. Evolutionary algorithms (Monte Carlo and self-consistent mean field) and assisted model building with energy refinement were used to optimize the peptide sequence in silico, while fluorescence assays were developed and conducted to verify the in silico results and elucidate a 15-amino acid signature sequence (R-W-Q/N-H-X2-F-Pho-X-G/A-W-R-X2-G, where X can be most amino acids, and Pho is hydrophobic) that recognized the tRNA's fully modified anticodon stem and loop domain, hASL(Lys3)UUU. Peptides of this sequence specifically recognized and bound modified htRNA(Lys3)UUU with an affinity 10-fold higher than that of the starting sequence. Thus, this approach provides an effective means of predicting sequences of RNA binding peptides that have better binding properties. Such peptides can be used in cell and molecular biology as well as biochemistry to explore RNA binding proteins and to inhibit those protein functions.

  10. Probabilistic Wind Power Ramp Forecasting Based on a Scenario Generation Method: Preprint

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

    Wang, Qin; Florita, Anthony R; Krishnan, Venkat K

    2017-08-31

    Wind power ramps (WPRs) are particularly important in the management and dispatch of wind power, and they are currently drawing the attention of balancing authorities. With the aim to reduce the impact of WPRs for power system operations, this paper develops a probabilistic ramp forecasting method based on a large number of simulated scenarios. An ensemble machine learning technique is first adopted to forecast the basic wind power forecasting scenario and calculate the historical forecasting errors. A continuous Gaussian mixture model (GMM) is used to fit the probability distribution function (PDF) of forecasting errors. The cumulative distribution function (CDF) ismore » analytically deduced. The inverse transform method based on Monte Carlo sampling and the CDF is used to generate a massive number of forecasting error scenarios. An optimized swinging door algorithm is adopted to extract all the WPRs from the complete set of wind power forecasting scenarios. The probabilistic forecasting results of ramp duration and start time are generated based on all scenarios. Numerical simulations on publicly available wind power data show that within a predefined tolerance level, the developed probabilistic wind power ramp forecasting method is able to predict WPRs with a high level of sharpness and accuracy.« less

  11. Protein classification using modified n-grams and skip-grams.

    PubMed

    Islam, S M Ashiqul; Heil, Benjamin J; Kearney, Christopher Michel; Baker, Erich J

    2018-05-01

    Classification by supervised machine learning greatly facilitates the annotation of protein characteristics from their primary sequence. However, the feature generation step in this process requires detailed knowledge of attributes used to classify the proteins. Lack of this knowledge risks the selection of irrelevant features, resulting in a faulty model. In this study, we introduce a supervised protein classification method with a novel means of automating the work-intensive feature generation step via a Natural Language Processing (NLP)-dependent model, using a modified combination of n-grams and skip-grams (m-NGSG). A meta-comparison of cross-validation accuracy with twelve training datasets from nine different published studies demonstrates a consistent increase in accuracy of m-NGSG when compared to contemporary classification and feature generation models. We expect this model to accelerate the classification of proteins from primary sequence data and increase the accessibility of protein characteristic prediction to a broader range of scientists. m-NGSG is freely available at Bitbucket: https://bitbucket.org/sm_islam/mngsg/src. A web server is available at watson.ecs.baylor.edu/ngsg. erich_baker@baylor.edu. Supplementary data are available at Bioinformatics online.

  12. Guidelines Curb Cuts and Ramps for Disabled Persons

    DOT National Transportation Integrated Search

    1995-07-01

    These guidelines for curb ramps were developed as part of an overall program of action to remove the restrictive barriers which severely impede the daily movements of physically handicapped and elderly persons. The common curb is probably the most en...

  13. Wrong-way driving at selected interstate off-ramps.

    DOT National Transportation Integrated Search

    1980-01-01

    This study was designed to evaluate, on interstate roadways in Virginia, the use of a technique developed in California for estimating or determining incidences of wrong-way driving at off-ramps. Also, information gained from a survey of the availabl...

  14. Biomechanics of ramp descent in unilateral trans-tibial amputees: Comparison of a microprocessor controlled foot with conventional ankle-foot mechanisms.

    PubMed

    Struchkov, Vasily; Buckley, John G

    2016-02-01

    Walking down slopes and/or over uneven terrain is problematic for unilateral trans-tibial amputees. Accordingly, 'ankle' devices have been added to some dynamic-response feet. This study determined whether use of a microprocessor controlled passive-articulating hydraulic ankle-foot device improved the gait biomechanics of ramp descent in comparison to conventional ankle-foot mechanisms. Nine active unilateral trans-tibial amputees repeatedly walked down a 5° ramp, using a hydraulic ankle-foot with microprocessor active or inactive or using a comparable foot with rubber ball-joint (elastic) 'ankle' device. When inactive the hydraulic unit's resistances were those deemed to be optimum for level-ground walking, and when active, the plantar- and dorsi-flexion resistances switched to a ramp-descent mode. Residual limb kinematics, joints moments/powers and prosthetic foot power absorption/return were compared across ankle types using ANOVA. Foot-flat was attained fastest with the elastic foot and second fastest with the active hydraulic foot (P<0.001). Prosthetic shank single-support mean rotation velocity (p =0.006), and the flexion (P<0.001) and negative work done at the residual knee (P=0.08) were reduced, and negative work done by the ankle-foot increased (P<0.001) when using the active hydraulic compared to the other two ankle types. The greater negative 'ankle' work done when using the active hydraulic compared to other two ankle types, explains why there was a corresponding reduction in flexion and negative work at the residual knee. These findings suggest that use of a microprocessor controlled hydraulic foot will reduce the biomechanical compensations used to walk down slopes. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Plant nuclear pore complex proteins are modified by novel oligosaccharides with terminal N-acetylglucosamine.

    PubMed Central

    Heese-Peck, A; Cole, R N; Borkhsenious, O N; Hart, G W; Raikhel, N V

    1995-01-01

    Only a few nuclear pore complex (NPC) proteins, mainly in vertebrates and yeast but none in plants, have been well characterized. As an initial step to identify plant NPC proteins, we examined whether NPC proteins from tobacco are modified by N-acetylglucosamine (GlcNAc). Using wheat germ agglutinin, a lectin that binds specifically to GlcNAc in plants, specific labeling was often found associated with or adjacent to NPCs. Nuclear proteins containing GlcNAc can be partially extracted by 0.5 M salt, as shown by a wheat germ agglutinin blot assay, and at least eight extracted proteins were modified by terminal GlcNAc, as determined by in vitro galactosyltransferase assays. Sugar analysis indicated that the plant glycans with terminal GlcNAc differ from the single O-linked GlcNAc of vertebrate NPC proteins in that they consist of oligosaccharides that are larger in size than five GlcNAc residues. Most of these appear to be bound to proteins via a hydroxyl group. This novel oligosaccharide modification may convey properties to the plant NPC that are different from those of vertebrate NPCs. PMID:8589629

  16. 29 CFR 1918.25 - Bridge plates and ramps (See also § 1918.86).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 7 2011-07-01 2011-07-01 false Bridge plates and ramps (See also § 1918.86). 1918.25... Means of Access § 1918.25 Bridge plates and ramps (See also § 1918.86). (a) Bridge and car plates (dockboards). Bridge and car plates used afloat shall be well maintained and shall: (1) Be strong enough to...

  17. 29 CFR 1918.25 - Bridge plates and ramps (See also § 1918.86).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 7 2010-07-01 2010-07-01 false Bridge plates and ramps (See also § 1918.86). 1918.25... Means of Access § 1918.25 Bridge plates and ramps (See also § 1918.86). (a) Bridge and car plates (dockboards). Bridge and car plates used afloat shall be well maintained and shall: (1) Be strong enough to...

  18. Experimental investigation of a supersonic swept ramp injector using laser-induced iodine fluorescence

    NASA Technical Reports Server (NTRS)

    Hartfield, Roy J.; Hollo, Steven D.; Mcdaniel, James C.

    1990-01-01

    Planar measurements of injectant mole fraction and temperature have been conducted in a nonreacting supersonic combustor configured with underexpanded injection in the base of a swept ramp. The temperature measurements were conducted with a Mach 2 test section inlet in streamwise planes perpendicular to the test section wall on which the ramp was mounted. Injection concentration measurements, conducted in cross flow planes with both Mach 2 and Mach 2.9 free stream conditions, dramatically illustrate the domination of the mixing process by streamwise vorticity generated by the ramp. These measurements, conducted using a nonintrusive optical technique (laser-induced iodine fluorescence), provide an accurate and extensive experimental data base for the validation of computation fluid dynamic codes for the calculation of highly three-dimensional supersonic combustor flow fields.

  19. Development and evaluation of RAMP I - a practitioner's tool for screening of musculoskeletal disorder risk factors in manual handling.

    PubMed

    Lind, Carl Mikael; Forsman, Mikael; Rose, Linda Maria

    2017-10-16

    RAMP I is a screening tool developed to support practitioners in screening for work-related musculoskeletal disorder risk factors related to manual handling. RAMP I, which is part of the RAMP tool, is based on research-based studies combined with expert group judgments. More than 80 practitioners participated in the development of RAMP I. The tool consists of dichotomous assessment items grouped into seven categories. Acceptable reliability was found for a majority of the assessment items for 15 practitioners who were given 1 h of training. The usability evaluation points to RAMP I being usable for screening for musculoskeletal disorder risk factors, i.e., usable for assessing risks, being usable as a decision base, having clear results and that the time needed for an assessment is acceptable. It is concluded that RAMP I is a usable tool for practitioners.

  20. Classification and Surgical Repair of Ramp Lesions of the Medial Meniscus.

    PubMed

    Thaunat, Mathieu; Fayard, Jean Marie; Guimaraes, Tales M; Jan, Nicolas; Murphy, Colin G; Sonnery-Cottet, Bertrand

    2016-08-01

    Ramp lesions of the medial meniscus are commonly associated with anterior cruciate ligament ruptures and consist of longitudinal peripheral tears of the posterior horn of the medial meniscus. Given the frequency of partial-thickness tears, they can be difficult to diagnose arthroscopically from the anterior compartment. We describe a classification of the different types of ramp lesions depending on both tear pattern (partial- or full-thickness tear) and associated meniscotibial ligament disruption. An original technique of arthroscopic suture placement through a single posteromedial portal with a 25° curved suture hook device is described.

  1. Acetylation of pregnane X receptor protein determines selective function independent of ligand activation

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

    Biswas, Arunima; Pasquel, Danielle; Tyagi, Rakesh Kumar

    2011-03-18

    Research highlights: {yields} Pregnane X receptor (PXR), a major regulatory protein, is modified by acetylation. {yields} PXR undergoes dynamic deacetylation upon ligand-mediated activation. {yields} SIRT1 partially mediates PXR deacetylation. {yields} PXR deacetylation per se induces lipogenesis mimicking ligand-mediated activation. -- Abstract: Pregnane X receptor (PXR), like other members of its class of nuclear receptors, undergoes post-translational modification [PTM] (e.g., phosphorylation). However, it is unknown if acetylation (a major and common form of protein PTM) is observed on PXR and, if it is, whether it is of functional consequence. PXR has recently emerged as an important regulatory protein with multiple ligand-dependentmore » functions. In the present work we show that PXR is indeed acetylated in vivo. SIRT1 (Sirtuin 1), a NAD-dependent class III histone deacetylase and a member of the sirtuin family of proteins, partially mediates deacetylation of PXR. Most importantly, the acetylation status of PXR regulates its selective function independent of ligand activation.« less

  2. Prediction based active ramp metering control strategy with mobility and safety assessment

    NASA Astrophysics Data System (ADS)

    Fang, Jie; Tu, Lili

    2018-04-01

    Ramp metering is one of the most direct and efficient motorway traffic flow management measures so as to improve traffic conditions. However, owing to short of traffic conditions prediction, in earlier studies, the impact on traffic flow dynamics of the applied RM control was not quantitatively evaluated. In this study, a RM control algorithm adopting Model Predictive Control (MPC) framework to predict and assess future traffic conditions, which taking both the current traffic conditions and the RM-controlled future traffic states into consideration, was presented. The designed RM control algorithm targets at optimizing the network mobility and safety performance. The designed algorithm is evaluated in a field-data-based simulation. Through comparing the presented algorithm controlled scenario with the uncontrolled scenario, it was proved that the proposed RM control algorithm can effectively relieve the congestion of traffic network with no significant compromises in safety aspect.

  3. Temporal gradients in shear stimulate osteoblastic proliferation via ERK1/2 and retinoblastoma protein

    NASA Technical Reports Server (NTRS)

    Jiang, Guang-Liang; White, Charles R.; Stevens, Hazel Y.; Frangos, John A.

    2002-01-01

    Bone cells are subject to interstitial fluid flow (IFF) driven by venous pressure and mechanical loading. Rapid dynamic changes in mechanical loading cause transient gradients in IFF. The effects of pulsatile flow (temporal gradients in fluid shear) on rat UMR106 cells and rat primary osteoblastic cells were studied. Pulsatile flow induced a 95% increase in S-phase UMR106 cells compared with static controls. In contrast, ramped steady flow stimulated only a 3% increase. Similar patterns of S-phase induction were also observed in rat primary osteoblastic cells. Pulsatile flow significantly increased relative UMR106 cell number by 37 and 62% at 1.5 and 24 h, respectively. Pulsatile flow also significantly increased extracellular signal-regulated kinase (ERK1/2) phosphorylation by 418%, whereas ramped steady flow reduced ERK1/2 activation to 17% of control. Correspondingly, retinoblastoma protein was significantly phosphorylated by pulsatile fluid flow. Inhibition of mitogen-activated protein (MAP)/ERK kinase (MEK)1/2 by U0126 (a specific MEK1/2 inhibitor) reduced shear-induced ERK1/2 phosphorylation and cell proliferation. These findings suggest that temporal gradients in fluid shear stress are potent stimuli of bone cell proliferation.

  4. Integrated database and analysis system for the evaluation of freeway corridors for potential ramp signaling.

    DOT National Transportation Integrated Search

    2011-11-15

    Ramp signaling is a relatively low-cost traffic management strategy that aims to improve the flow of : traffic by controlling the rate at which vehicles enter the freeway. While studies have shown that ramp : signaling helps to alleviate traffic cong...

  5. Comparison of new nitrosoureas esters with modified steroidal nucleus for cytogenetic and antineoplastic activity.

    PubMed

    Hussein, A; Mioglou-Kalouptsi, E; Papageorgiou, A; Karapidaki, I; Iakovidou-Kritsi, Z; Lialiaris, T; Xrysogelou, E; Camoutsis, C; Mourelatos, D

    2007-01-01

    Nitrosourea is decomposed under physiological conditions to react with biological macromolecules by two mechanisms: alkylation (with proteins and nucleic acids) and carbamoylation (with proteins but not nucleic acids). It has been suggested that the alkylating action is responsible for the therapeutic effects of nitrosoureas, and that the carbamoylation activity leads to toxicity effects. In order to reduce systemic toxicity and improve specificity and distribution for cancer therapy, 2-haloethyl nitrosourea has been esterified with modified steroids, which are used as biological platforms for transporting the alkylating agent to the tumor site in a specific manner. The cytogenetic and antineoplastic effect were studied of seven newly synthesized esters of N,N-bis(2-chloroethyl)alanyl carboxyl derivatives with a modified steroidal nucleus (compounds 1-7). As a very sensitive indicator of genotoxicity the Sister Chromatid Exchange (SCE) assay was used and as a valuable marker of cytostatic activity the cell Proliferation Rate Index (PRI) in cultures of normal human lymphocytes was used. The order of magnitude of the cytogenetic activity on a molar basis (15, 30, 120 microM) of the compounds was 7>6>3>5>2>4>1. The most active compound 7 has an enlarged (seven carbon atoms) A ring modified with a lactam group (-NHCO-) with the nitrosourea moiety esterified at position 17 In the group of seven substances a correlation was observed between the magnitude of SCE response and the depression in PRI (r=-O, 65, p<0.001). According to the criterion of activity of National Cancer Institute (NCI), the order of antineoplastic activity of compounds on lymphoid L1210 leukemia is 7>6>2>5>4>3>1 and on lympocytic P388 leukemia cells is 7>2>6>5>4>3>1. The present results are in agreement with previous suggestions that the effectiveness in cytogenetic activity may well be correlated with antitumor effects [T/C: 248% for the compound 7 in 250 mg/kg b.w.; T/C: mean survival time of drug

  6. Direct analysis of in-gel proteins by carbon nanotubes-modified paper spray ambient mass spectrometry.

    PubMed

    Han, Feifei; Yang, Yuhan; Ouyang, Jin; Na, Na

    2015-02-07

    The in situ and direct extraction, desorption and ionization of in-gel intact proteins after electrophoresis has been achieved by carbon nanotubes (CNTs)-modified paper spray mass spectrometry at ambient conditions. Characteristics of CNTs (including larger surface area, smaller pore diameter and enhanced conductivity) were endowed to the porous filter paper substrate by uniformly dispersing the CNTs on the filter paper. Upon applying electric potential to the CNTs-modified paper, the in-gel proteins were extracted from the gel and subsequently migrated to the tip of the filter paper by electrophoresis-like behavior for paper spray ionization, which was monitored by extracted ion chronograms. The characterizations of modified filter papers and CNTs nanoparticles further confirmed the role of CNTs in in-gel protein extraction, protein migration as well as spray ionization at the paper tip. Under optimized conditions, a mixture of cytochrome c, lysozyme and myoglobin was successfully separated by native electrophoresis and subsequently analysed by the present method, showing a limit of detection of 10 ng per gel band. The present strategy offers a new pathway for the direct detection of in-gel intact proteins at ambient conditions without any pre-treatment (e.g. digestion, chemical extraction and desalting), which exhibits potential applications in top-down proteomics.

  7. 40 CFR 1042.505 - Testing engines using discrete-mode or ramped-modal duty cycles.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 32 2010-07-01 2010-07-01 false Testing engines using discrete-mode or...-IGNITION ENGINES AND VESSELS Test Procedures § 1042.505 Testing engines using discrete-mode or ramped-modal... the Clean Air Act. (a) You may perform steady-state testing with either discrete-mode or ramped-modal...

  8. Development of criteria and guidelines for installing, operating, and removing TxDOT ramp control signals.

    DOT National Transportation Integrated Search

    2009-05-01

    The Texas Department of Transportation (TxDOT) uses ramp control signals (also called ramp meters or : flow signals) to control the rate at which vehicles enter the freeway. This helps TxDOT (1) promote a more : consistent and uniform flow of traffic...

  9. Experiencing Production Ramp-Up Education for Engineers

    ERIC Educational Resources Information Center

    Bassetto, S.; Fiegenwald, V.; Cholez, C.; Mangione, F.

    2011-01-01

    This paper presents a game of industrialisation, based on a paper airplane, that mimics real world production ramp-up and blends classical engineering courses together. It is based on a low cost product so that it can be mass produced. The game targets graduate students and practitioners in engineering fields. For students, it offers an experiment…

  10. A tunable electron beam source using trapping of electrons in a density down-ramp in laser wakefield acceleration.

    PubMed

    Ekerfelt, Henrik; Hansson, Martin; Gallardo González, Isabel; Davoine, Xavier; Lundh, Olle

    2017-09-25

    One challenge in the development of laser wakefield accelerators is to demonstrate sufficient control and reproducibility of the parameters of the generated bunches of accelerated electrons. Here we report on a numerical study, where we demonstrate that trapping using density down-ramps allows for tuning of several electron bunch parameters by varying the properties of the density down-ramp. We show that the electron bunch length is determined by the difference in density before and after the ramp. Furthermore, the transverse emittance of the bunch is controlled by the steepness of the ramp. Finally, the amount of trapped charge depends both on the density difference and on the steepness of the ramp. We emphasize that both parameters of the density ramp are feasible to vary experimentally. We therefore conclude that this tunable electron accelerator makes it suitable for a wide range of applications, from those requiring short pulse length and low emittance, such as the free-electron lasers, to those requiring high-charge, large-emittance bunches to maximize betatron X-ray generation.

  11. Evaluation of WRF-Predicted Near-Hub-Height Winds and Ramp Events over a Pacific Northwest Site with Complex Terrain

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

    Yang, Qing; Berg, Larry K.; Pekour, Mikhail

    The WRF model version 3.3 is used to simulate near hub-height winds and power ramps utilizing three commonly used planetary boundary-layer (PBL) schemes: Mellor-Yamada-Janjic (MYJ), University of Washington (UW), and Yonsei University (YSU). The predicted winds have small mean biases compared with observations. Power ramps and step changes (changes within an hour) consistently show that the UW scheme performed better in predicting up ramps under stable conditions with higher prediction accuracy and capture rates. Both YSU and UW scheme show good performance predicting up- and down- ramps under unstable conditions with YSU being slightly better for ramp durations longer thanmore » an hour. MYJ is the most successful simulating down-ramps under stable conditions. The high wind speed and large shear associated with low-level jets are frequently associated with power ramps, and the biases in predicted low-level jet explain some of the shown differences in ramp predictions among different PBL schemes. Low-level jets were observed as low as ~200 m in altitude over the Columbia Basin Wind Energy Study (CBWES) site, located in an area of complex terrain. The shear, low-level peak wind speeds, as well as the height of maximum wind speed are not well predicted. Model simulations with 3 PBL schemes show the largest variability among them under stable conditions.« less

  12. AMP-activated protein kinase and type 2 diabetes.

    PubMed

    Musi, Nicolas

    2006-01-01

    AMP-activated protein kinase (AMPK) is an enzyme that works as a fuel gauge, being activated in situations of high-energy phosphate depletion. Upon activation, AMPK functions to restore cellular ATP by modifying diverse metabolic pathways. AMPK is activated robustly by skeletal muscle contraction and myocardial ischemia, and may be involved in the stimulation of glucose transport and fatty acid oxidation produced by these stimuli. In liver, activation of AMPK results in enhanced fatty acid oxidation and in decreased production of glucose, cholesterol, and triglycerides. Recent studies have shown that AMPK is the cellular mediator for many of the metabolic effects of drugs such as metformin and thiazolidinediones, as well as the insulin sensitizing adipocytokines leptin and adiponectin. These data, along with evidence from studies showing that chemical activation of AMPK in vivo with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) improves blood glucose concentrations and lipid profiles, make this enzyme an attractive pharmacological target for the treatment of type 2 diabetes and other metabolic disorders.

  13. LC-MS display of the total modified amino acids in cataract lens proteins and in lens proteins glycated by ascorbic acid in vitro.

    PubMed

    Cheng, Rongzhu; Feng, Qi; Ortwerth, Beryl J

    2006-05-01

    We previously reported chromatographic evidence supporting the similarity of yellow chromophores isolated from aged human lens proteins, early brunescent cataract lens proteins and calf lens proteins ascorbylated in vitro [Cheng, R. et al. Biochimica et Biophysica Acta 1537, 14-26, 2001]. In this paper, new evidence supporting the chemical identity of the modified amino acids in these protein populations were collected by using a newly developed two-dimensional LC-MS mapping technique supported by tandem mass analysis of the major species. The pooled water-insoluble proteins from aged normal human lenses, early stage brunescent cataract lenses and calf lens proteins reacted with or without 20 mM ascorbic acid in air for 4 weeks were digested with a battery of proteolytic enzymes under argon to release the modified amino acids. Aliquots equivalent to 2.0 g of digested protein were subjected to size-exclusion chromatography on a Bio-Gel P-2 column and four major A330nm-absorbing peaks were collected. Peaks 1, 2 and 3, which contained most of the modified amino acids were concentrated and subjected to RP-HPLC/ESI-MS, and the mass elution maps were determined. The samples were again analyzed and those peaks with a 10(4) - 10(6) response factor were subjected to MS/MS analysis to identify the daughter ions of each modification. Mass spectrometric maps of peaks 1, 2 and 3 from cataract lenses showed 58, 40 and 55 mass values, respectively, ranging from 150 to 600 Da. Similar analyses of the peaks from digests of the ascorbylated calf lens proteins gave 81, 70 and 67 mass values, respectively, of which 100 were identical to the peaks in the cataract lens proteins. A total of 40 of the major species from each digest were analyzed by LC-MS/MS and 36 were shown to be identical. Calf lens proteins incubated without ascorbic acid showed several similar mass values, but the response factors were 100 to 1000-fold less for every modification. Based upon these data, we conclude

  14. Experimental and Computational Investigation of a Translating-Throat Single-Expansion-Ramp Nozzle

    NASA Technical Reports Server (NTRS)

    Deere, Karen A.; Asbury, Scott C.

    1999-01-01

    An experimental and computational study was conducted on a high-speed, single-expansion-ramp nozzle (SERN) concept designed for efficient off-design performance. The translating-throat SERN concept adjusts the axial location of the throat to provide a variable expansion ratio and allow a more optimum jet exhaust expansion at various flight conditions in an effort to maximize nozzle performance. Three design points (throat locations) were investigated to simulate the operation of this concept at subsonic-transonic, low supersonic, and high supersonic flight conditions. The experimental study was conducted in the jet exit test facility at the Langley Research Center. Internal nozzle performance was obtained at nozzle pressure ratios (NPR's) up to 13 for six nozzles with design nozzle pressure ratios near 9, 42, and 102. Two expansion-ramp surfaces, one concave and one convex, were tested for each design point. Paint-oil flow and focusing schlieren flow visualization techniques were utilized to acquire additional flow data at selected NPR'S. The Navier-Stokes code, PAB3D, was used with a two-equation k-e turbulence model for the computational study. Nozzle performance characteristics were predicted at nozzle pressure ratios of 5, 9, and 13 for the concave ramp, low Mach number nozzle and at 10, 13, and 102 for the concave ramp, high Mach number nozzle.

  15. Identification of liver protein targets modified by tienilic acid metabolites using a two-dimensional Western blot-mass spectrometry approach

    NASA Astrophysics Data System (ADS)

    Methogo, Ruth Menque; Dansette, Patrick M.; Klarskov, Klaus

    2007-12-01

    A combined approach based on two-dimensional electrophoresis-immuno-blotting and nanoliquid chromatography coupled on-line with electrospray ionization mass spectrometry (nLC-MS/MS) was used to identify proteins modified by a reactive intermediate of tienilic acid (TA). Liver homogenates from rats exposed to TA were fractionated using ultra centrifugation; four fractions were obtained and subjected to 2D electrophoresis. Following transfer to PVDF membranes, modified proteins were visualized after India ink staining, using an anti-serum raised against TA and ECL detection. Immuno-reactive spots were localized on the PVDF membrane by superposition of the ECL image, protein spots of interest were excised, digested on the membrane with trypsin followed by nLC-MS/MS analysis and protein identification. A total of 15 proteins were identified as likely targets modified by a TA reactive metabolite. These include selenium binding protein 2, senescence marker protein SMP-30, adenosine kinase, Acy1 protein, adenosylhomocysteinase, capping protein (actin filament), protein disulfide isomerase, fumarylacetoacetase, arginase chain A, ketohexokinase, proteasome endopeptidase complex, triosephosphate isomerase, superoxide dismutase, dna-type molecular chaperone hsc73 and malate dehydrogenase.

  16. Effects of onion extract on endogenous vascular H2S and adrenomedulin in rat atherosclerosis.

    PubMed

    Li, Wei; Tang, Chaoshu; Jin, Hongfang; Du, Junbao

    2011-09-01

    This study aimed to explore the effect of onion extract on endogenous hydrogen sulfide (H2S) and adrenomedulin (ADM) and on atherosclerotic progression in rats with atherosclerosis (AS). Male Sprague-Dawley rats were randomly divided into control, AS and AS+onion groups. Ultrastructure of aorta and atherosclerotic lesions both in aorta and in coronary artery were detected. Plasma and aortic H2S were detected by using a sulfide- sensitive electrode. Plasma and aortic ADM was determined with radioimmunoassay. Cystathionine-γ-lyase (CSE), calcitonin receptor-like receptor (CRLR), receptor activity-modifying protein (RAMP1, RAMP2 and RAMP3) mRNA expressions were analysed. Glutathione peroxidase (GSH-PX), superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO) and NO synthase (NOS) contents in plasma, SOD1, SOD2 and ICAM-1 expressions in aorta were detected. Rats in the AS group showed marked atherosclerotic lesions both in aorta and in coronary artery but decreased aortic H2S production. Decreased plasma and aortic ADM content, but increased levels of aortic CRLR, RAMP2 and RAMP3 mRNAs were observed. Plasma GSH-PX and SOD were reduced but MDA elevated. Plasma ICAM-1 and NO contents and iNOS activity were increased. Onion extract, however, lessened atherosclerotic lesions and increased endogenous aortic H2S production, but decreased plasma ADM content, aortic ADM content and aortic CRLR, RAMP2 and RAMP3 mRNAs. In addition, it increased plasma GSH-PX level and SOD activities but reduced MDA; it decreased inflammatory response but increased plasma eNOS activity and NO content. Onion extract exerted a marked antiatherogenic effect in association with the up-regulation of the endogenous CSE/H2S pathway but down-regulation of the ADM/CRLR family in atherosclerotic rats.

  17. Resident-Assisted Montessori Programming (RAMP): use of a small group reading activity run by persons with dementia in adult day health care and long-term care settings.

    PubMed

    Skrajner, Michael J; Camp, Cameron J

    2007-01-01

    Six persons in the early to middle stages of dementia ("leaders") were trained in Resident-Assisted Montessori Programming (RAMP) to lead a reading activity for 22 persons with more advanced dementia ("participants") in an adult day health center (ADHC) and a special care unit (SCU) in a skilled nursing facility. Researchers assessed the leaders' abilities to learn and follow the procedures of leading a group, as well as their satisfaction with their roles. In addition, participants' engagement and affect were measured, both during standard activities programming and during client-led activities. Results of this study suggest that persons with dementia can indeed successfully lead small group activities, if several important prerequisites are met. Furthermore, the engagement and affect of participants was more positive in client-led activities than in standard activities programming.

  18. Involvement of protein kinase B and mitogen-activated protein kinases in experimental normothermic liver ischaemia-reperfusion injury.

    PubMed

    Cursio, R; Filippa, N; Miele, C; Van Obberghen, E; Gugenheim, J

    2006-06-01

    This study evaluated the role of protein kinase B (PKB), phosphatidylinositol 3-kinase (PI3-K), Bcl-2-associated death protein (BAD) and mitogen-activated protein kinases (MAPKs) in normothermic ischaemia-reperfusion (IR)-induced apoptosis in rat liver. Rats were divided into two groups that received either phosphate-buffered saline (control) or the caspase inhibitor Z-Asp-2,6-dichorobenzoyloxymethylketone (Z-Asp-cmk), injected intravenously 2 min before the induction of 120 min of normothermic liver ischaemia. Liver apoptosis was assessed by the terminal deoxyribonucleotidyltransferase-mediated dUTP nick end labelling (TUNEL) method. PI3-K, PKB, BAD and MAPK activities were measured in ischaemic and non-ischaemic lobes at various times after reperfusion. The number of TUNEL-positive cells was significantly decreased after pretreatment with Z-Asp-cmk. In controls, PI3-K and PKB activities and BAD phosphorylation were inhibited in ischaemic liver lobes. The MAPKs (extracellular signal-regulated kinases, c-Jun N-terminal kinase and p38) showed different patterns of activation during IR. PKB activity was not modified by pretreatment with Z-Asp-cmk. Induction of apoptosis during IR liver injury might be triggered by inactivation of the antiapoptotic PI3-K-PKB pathway and activation of the proapoptotic MAPKs. Copyright (c) 2006 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

  19. Non-stationary self-focusing of intense laser beam in plasma using ramp density profile

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

    Habibi, M.; Ghamari, F.

    2011-10-15

    The non-stationary self-focusing of high intense laser beam in under-dense plasma with upward increasing density ramp is investigated. The obtained results show that slowly increasing plasma density ramp is very important in enhancing laser self-focusing. Also, the spot size oscillations of laser beam in front and rear of the pulse for two different density profiles are shown. We have selected density profiles that already were used by Sadighi-Bonabi et al.[Phys. Plasmas 16, 083105 (2009)]. Ramp density profile causes the laser beam to become more focused and penetrations deeps into the plasma by reduction of diffraction effects. Our computations show moremore » reliable results in comparison to the previous works.« less

  20. PDK1-dependent activation of atypical PKC leads to degradation of the p21 tumour modifier protein

    PubMed Central

    Scott, Mary T.; Ingram, Angela; Ball, Kathryn L.

    2002-01-01

    p21WAF1/CIP1 contributes to positive and negative growth control on multiple levels. We previously mapped phosphorylation sites within the C-terminal domain of p21 that regulate proliferating cell nucear antigen binding. In the current study, a kinase has been fractionated from mammalian cells that stoichiometrically phosphorylates p21 at the Ser146 site, and the enzyme has been identified as an insulin-responsive atypical protein kinase C (aPKC). Expression of PKCζ or activation of the endogenous kinase by 3-phosphoinositide dependent protein kinase-1 (PDK1) decreased the half-life of p21. Conversely, dnPKCζ or dnPDK1 increased p21 protein half-life, and a PDK1-dependent increase in the rate of p21 degradation was mediated by aPKC. Insulin stimulation gave a biphasic response with a rapid transient decrease in p21 protein levels during the initial signalling phase that was dependent on phosphatidylinositol 3- kinase, PKC and proteasome activity. Thus, aPKC provides a physiological signal for the degradation of p21. The rapid degradation of p21 protein during the signalling phase of insulin stimulation identifies a novel link between energy metabolism and a key modulator of cell cycle progression. PMID:12485998

  1. Heat dissipation guides activation in signaling proteins.

    PubMed

    Weber, Jeffrey K; Shukla, Diwakar; Pande, Vijay S

    2015-08-18

    Life is fundamentally a nonequilibrium phenomenon. At the expense of dissipated energy, living things perform irreversible processes that allow them to propagate and reproduce. Within cells, evolution has designed nanoscale machines to do meaningful work with energy harnessed from a continuous flux of heat and particles. As dictated by the Second Law of Thermodynamics and its fluctuation theorem corollaries, irreversibility in nonequilibrium processes can be quantified in terms of how much entropy such dynamics produce. In this work, we seek to address a fundamental question linking biology and nonequilibrium physics: can the evolved dissipative pathways that facilitate biomolecular function be identified by their extent of entropy production in general relaxation processes? We here synthesize massive molecular dynamics simulations, Markov state models (MSMs), and nonequilibrium statistical mechanical theory to probe dissipation in two key classes of signaling proteins: kinases and G-protein-coupled receptors (GPCRs). Applying machinery from large deviation theory, we use MSMs constructed from protein simulations to generate dynamics conforming to positive levels of entropy production. We note the emergence of an array of peaks in the dynamical response (transient analogs of phase transitions) that draw the proteins between distinct levels of dissipation, and we see that the binding of ATP and agonist molecules modifies the observed dissipative landscapes. Overall, we find that dissipation is tightly coupled to activation in these signaling systems: dominant entropy-producing trajectories become localized near important barriers along known biological activation pathways. We go on to classify an array of equilibrium and nonequilibrium molecular switches that harmonize to promote functional dynamics.

  2. Structural and Functional Analysis of a Novel Interaction Motif within UFM1-activating Enzyme 5 (UBA5) Required for Binding to Ubiquitin-like Proteins and Ufmylation*

    PubMed Central

    Habisov, Sabrina; Huber, Jessica; Ichimura, Yoshinobu; Akutsu, Masato; Rogova, Natalia; Loehr, Frank; McEwan, David G.; Johansen, Terje; Dikic, Ivan; Doetsch, Volker; Komatsu, Masaaki; Rogov, Vladimir V.; Kirkin, Vladimir

    2016-01-01

    The covalent conjugation of ubiquitin-fold modifier 1 (UFM1) to proteins generates a signal that regulates transcription, response to cell stress, and differentiation. Ufmylation is initiated by ubiquitin-like modifier activating enzyme 5 (UBA5), which activates and transfers UFM1 to ubiquitin-fold modifier-conjugating enzyme 1 (UFC1). The details of the interaction between UFM1 and UBA5 required for UFM1 activation and its downstream transfer are however unclear. In this study, we described and characterized a combined linear LC3-interacting region/UFM1-interacting motif (LIR/UFIM) within the C terminus of UBA5. This single motif ensures that UBA5 binds both UFM1 and light chain 3/γ-aminobutyric acid receptor-associated proteins (LC3/GABARAP), two ubiquitin (Ub)-like proteins. We demonstrated that LIR/UFIM is required for the full biological activity of UBA5 and for the effective transfer of UFM1 onto UFC1 and a downstream protein substrate both in vitro and in cells. Taken together, our study provides important structural and functional insights into the interaction between UBA5 and Ub-like modifiers, improving the understanding of the biology of the ufmylation pathway. PMID:26929408

  3. Atomic layer deposition modified track-etched conical nanochannels for protein sensing.

    PubMed

    Wang, Ceming; Fu, Qibin; Wang, Xinwei; Kong, Delin; Sheng, Qian; Wang, Yugang; Chen, Qiang; Xue, Jianming

    2015-08-18

    Nanopore-based devices have recently become popular tools to detect biomolecules at the single-molecule level. Unlike the long-chain nucleic acids, protein molecules are still quite challenging to detect, since the protein molecules are much smaller in size and usually travel too fast through the nanopore with poor signal-to-noise ratio of the induced transport signals. In this work, we demonstrate a new type of nanopore device based on atomic layer deposition (ALD) Al2O3 modified track-etched conical nanochannels for protein sensing. These devices show very promising properties of high protein (bovine serum albumin) capture rate with well time-resolved transport signals and excellent signal-to-noise ratio for the transport events. Also, a special mechanism involving transient process of ion redistribution inside the nanochannel is proposed to explain the unusual biphasic waveshapes of the current change induced by the protein transport.

  4. Block copolymer modified surfaces for conjugation of biomacromolecules with control of quantity and activity.

    PubMed

    Li, Xin; Wang, Mengmeng; Wang, Lei; Shi, Xiujuan; Xu, Yajun; Song, Bo; Chen, Hong

    2013-01-29

    Polymer brush layers based on block copolymers of poly(oligo(ethylene glycol) methacrylate) (POEGMA) and poly(glycidyl methacrylate) (PGMA) were formed on silicon wafers by activators generated by electron transfer atom transfer radical polymerization (AGET ATRP). Different types of biomolecule can be conjugated to these brush layers by reaction of PGMA epoxide groups with amino groups in the biomolecule, while POEGMA, which resists nonspecific protein adsorption, provides an antifouling environment. Surfaces were characterized by water contact angle, ellipsometry, and Fourier transform infrared spectroscopy (FTIR) to confirm the modification reactions. Phase segregation of the copolymer blocks in the layers was observed by AFM. The effect of surface properties on protein conjugation was investigated using radiolabeling methods. It was shown that surfaces with POEGMA layers were protein resistant, while the quantity of protein conjugated to the diblock copolymer modified surfaces increased with increasing PGMA layer thickness. The activity of lysozyme conjugated on the surface could also be controlled by varying the thickness of the copolymer layer. When biotin was conjugated to the block copolymer grafts, the surface remained resistant to nonspecific protein adsorption but showed specific binding of avidin. These properties, that is, well-controlled quantity and activity of conjugated biomolecules and specificity of interaction with target biomolecules may be exploited for the improvement of signal-to-noise ratio in sensor applications. More generally, such surfaces may be useful as biological recognition elements of high specificity for functional biomaterials.

  5. Tailored ramp wave generation in gas gun experiments

    NASA Astrophysics Data System (ADS)

    Cotton, Matthew; Chapman, David; Winter, Ron; Harris, Ernie; Eakins, Daniel

    2015-09-01

    Gas guns are traditionally used as platforms to introduce a planar shock wave to a material using plate impact methods, generating states on the Hugoniot. The ability to deliver a ramp wave to a target during a gas gun experiment enables access to different regions of the equation-of-state surface, making it a valuable technique for characterising material behaviour. Previous techniques have relied on the use of multi-material impactors to generate a density gradient, which can be complex to manufacture. In this paper we describe the use of an additively manufactured steel component consisting of an array of tapered spikes which can deliver a ramp wave over ˜ 2 μs. The ability to tailor the input wave by varying the component design is discussed, an approach which makes use of the design freedom offered by additive manufacturing techniques to rapidly iterate the spike profile. Results from gas gun experiments are presented to evaluate the technique, and compared with 3D hydrodynamic simulations.

  6. Letter: Transient interaction between plasma jet and supersonic compression ramp flow

    NASA Astrophysics Data System (ADS)

    Huang, He-Xia; Tan, Hui-Jun; Sun, Shu; Zhang, Yu-Chao; Cheng, Lin

    2018-04-01

    The rapid flow evolution between a plasma jet and a 20° compression ramp flow is captured by a high-speed schlieren system at Mach 2.0. Several interesting flow phenomena are observed for the first time. The pulsed jet, which generates strong perturbations, forces the crossflow boundary layer to separate and forms a forward moving shock. A typical shock-on-shock interaction occurs when the precursor shock intersects with the original shock. The interaction is initially regular, and then it transforms into an irregular one with a Mach stem connecting the precursor shock and original ramp shock.

  7. Controlled release of NELL-1 protein from chitosan/hydroxyapatite-modified TCP particles.

    PubMed

    Zhang, Yulong; Dong, Rui; Park, Yujin; Bohner, Marc; Zhang, Xinli; Ting, Kang; Soo, Chia; Wu, Benjamin M

    2016-09-10

    NEL-like molecule-1 (NELL-1) is a novel osteogenic protein that showing high specificity to osteochondral cells. It was widely used in bone regeneration research by loading onto carriers such as tricalcium phosphate (TCP) particles. However, there has been little research on protein controlled release from this material and its potential application. In this study, TCP was first modified with a hydroxyapatite coating followed by a chitosan coating to prepare chitosan/hydroxyapatite-coated TCP particles (Chi/HA-TCP). The preparation was characterized by SEM, EDX, FTIR, XRD, FM and Zeta potential measurements. The NELL-1 loaded Chi/HA-TCP particles and the release kinetics were investigated in vitro. It was observed that the Chi/HA-TCP particles prepared with the 0.3% (wt/wt) chitosan solution were able to successfully control the release of NELL-1 and maintain a slow, steady release for up to 28 days. Furthermore, more than 78% of the loaded protein's bioactivity was preserved in Chi/HA-TCP particles over the period of the investigation, which was significantly higher than that of the protein released from hydroxyapatite coated TCP (HA-TCP) particles. Collectively, this study suggests that the osteogenic protein NELL-1 showed a sustained release pattern after being encapsulated into the modified Chi/HA-TCP particles, and the NELL-1 integrated composite of Chi/HA-TCP showed a potential to function as a protein delivery carrier and as an improved bone matrix for use in bone regeneration research. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Identify Secretory Protein of Malaria Parasite with Modified Quadratic Discriminant Algorithm and Amino Acid Composition.

    PubMed

    Feng, Yong-E

    2016-06-01

    Malaria parasite secretes various proteins in infected red blood cell for its growth and survival. Thus identification of these secretory proteins is important for developing vaccine or drug against malaria. In this study, the modified method of quadratic discriminant analysis is presented for predicting the secretory proteins. Firstly, 20 amino acids are divided into five types according to the physical and chemical characteristics of amino acids. Then, we used five types of amino acids compositions as inputs of the modified quadratic discriminant algorithm. Finally, the best prediction performance is obtained by using 20 amino acid compositions, the sensitivity of 96 %, the specificity of 92 % with 0.88 of Mathew's correlation coefficient in fivefold cross-validation test. The results are also compared with those of existing prediction methods. The compared results shown our method are prominent in the prediction of secretory proteins.

  9. Biological activity of a genetically modified BMP-2 variant with inhibitory activity

    PubMed Central

    Klammert, Uwe; Nickel, Joachim; Würzler, Kristian; Klingelhöffer, Christoph; Sebald, Walter; Kübler, Alexander C; Reuther, Tobias

    2009-01-01

    Background Alterations of the binding epitopes of bone morphogenetic protein-2 (BMP-2) lead to a modified interaction with the ectodomains of BMP receptors. In the present study the biological effect of a BMP-2 double mutant with antagonistic activity was evaluated in vivo. Methods Equine-derived collagenous carriers were loaded with recombinant human BMP-2 (rhBMP-2) in a well-known dose to provide an osteoinductive stimulus. The study was performed in a split animal design: carriers only coupled with rhBMP-2 (control) were implanted into prepared cavities of lower limb muscle of rats, specimens coupled with rhBMP-2 as well as BMP-2 double mutant were placed into the opposite limb in the same way. After 28 days the carriers were explanted, measured radiographically and characterized histologically. Results As expected, the BMP-2 loaded implants showed a typical heterotopic bone formation. The specimens coupled with both proteins showed a significant decreased bone formation in a dose dependent manner. Conclusion The antagonistic effect of a specific BMP-2 double mutant could be demonstrated in vivo. The dose dependent influence on heterotopic bone formation by preventing rhBMP-2 induced osteoinduction suggests a competitive receptor antagonism. PMID:19187528

  10. Folding behavior of ribosomal protein S6 studied by modified Go¯ -like model

    NASA Astrophysics Data System (ADS)

    Wu, L.; Zhang, J.; Wang, J.; Li, W. F.; Wang, W.

    2007-03-01

    Recent experimental and theoretical studies suggest that, although topology is the determinant factor in protein folding, especially for small single-domain proteins, energetic factors also play an important role in the folding process. The ribosomal protein S6 has been subjected to intensive studies. A radical change of the transition state in its circular permutants has been observed, which is believed to be caused by a biased distribution of contact energies. Since the simplistic topology-only Gō -like model is not able to reproduce such an observation, we modify the model by introducing variable contact energies between residues based on their physicochemical properties. The modified Gō -like model can successfully reproduce the Φ -value distributions, folding nucleus, and folding pathways of both the wild-type and circular permutants of S6. Furthermore, by comparing the results of the modified and the simplistic models, we find that the hydrophobic effect constructs the major force that balances the loop entropies. This may indicate that nature maintains the folding cooperativity of this protein by carefully arranging the location of hydrophobic residues in the sequence. Our study reveals a strategy or mechanism used by nature to get out of the dilemma when the native structure, possibly required by biological function, conflicts with folding cooperativity. Finally, the possible relationship between such a design of nature and amyloidosis is also discussed.

  11. Development of an innovative immunoassay for CP4EPSPS and Cry1AB genetically modified protein detection and quantification.

    PubMed

    Ermolli, M; Prospero, A; Balla, B; Querci, M; Mazzeo, A; Van Den Eede, G

    2006-09-01

    An innovative immunoassay, called enzyme-linked immunoabsorbant assay (ELISA) Reverse, based on a new conformation of the solid phase, was developed. The solid support was expressly designed to be immersed directly in liquid samples to detect the presence of protein targets. Its application is proposed in those cases where a large number of samples have to be screened simultaneously or when the simultaneous detection of different proteins is required. As a first application, a quantitative immunoassay for Cry1AB protein in genetically modified maize was optimized. The method was tested using genetically modified organism concentrations from 0.1 to 2.0%. The limit of detection and limit of quantitation of the method were determined as 0.0056 and 0.0168 (expressed as the percentage of genetically modified organisms content), respectively. A qualitative multiplex assay to assess the presence of two genetically modified proteins simultaneously was also established for the case of the Cry1AB and the CP4EPSPS (5-enolpyruvylshikimate-3-phosphate synthase) present in genetically modified maize and soy, respectively.

  12. 4. RAMP FOR BENJAMIN FRANKLIN BRIDGE (FOURTH ST.) BETWEEN VINE ...

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

    4. RAMP FOR BENJAMIN FRANKLIN BRIDGE (FOURTH ST.) BETWEEN VINE AND RACE STS., LOOKING NORTHWEST - Independence National Historical Park, Walnut, Sixth, Chestnut & Second Streets, Philadelphia, Philadelphia County, PA

  13. Root morphogenic pathways in Eucalyptus grandis are modified by the activity of protein arginine methyltransferases.

    PubMed

    Plett, Krista L; Raposo, Anita E; Bullivant, Stephen; Anderson, Ian C; Piller, Sabine C; Plett, Jonathan M

    2017-03-09

    Methylation of proteins at arginine residues, catalysed by members of the protein arginine methyltransferase (PRMT) family, is crucial for the regulation of gene transcription and for protein function in eukaryotic organisms. Inhibition of the activity of PRMTs in annual model plants has demonstrated wide-ranging involvement of PRMTs in key plant developmental processes, however, PRMTs have not been characterised or studied in long-lived tree species. Taking advantage of the recently available genome for Eucalyptus grandis, we demonstrate that most of the major plant PRMTs are conserved in E. grandis as compared to annual plants and that they are expressed in all major plant tissues. Proteomic and transcriptomic analysis in roots suggest that the PRMTs of E. grandis control a number of regulatory proteins and genes related to signalling during cellular/root growth and morphogenesis. We demonstrate here, using chemical inhibition of methylation and transgenic approaches, that plant type I PRMTs are necessary for normal root growth and branching in E. grandis. We further show that EgPRMT1 has a key role in root hair initiation and elongation and is involved in the methylation of β-tubulin, a key protein in cytoskeleton formation. Together, our data demonstrate that PRMTs encoded by E. grandis methylate a number of key proteins and alter the transcription of a variety of genes involved in developmental processes. Appropriate levels of expression of type I PRMTs are necessary for the proper growth and development of E. grandis roots.

  14. Tuning of protein-surfactant interaction to modify the resultant structure.

    PubMed

    Mehan, Sumit; Aswal, Vinod K; Kohlbrecher, Joachim

    2015-09-01

    Small-angle neutron scattering and dynamic light scattering studies have been carried out to examine the interaction of bovine serum albumin (BSA) protein with different surfactants under varying solution conditions. We show that the interaction of anionic BSA protein (pH7) with surfactant and the resultant structure are strongly modified by the charge head group of the surfactant, ionic strength of the solution, and mixed surfactants. The protein-surfactant interaction is maximum when two components are oppositely charged, followed by components being similarly charged through the site-specific binding, and no interaction in the case of a nonionic surfactant. This interaction of protein with ionic surfactants is characterized by the fractal structure representing a bead-necklace structure of micellelike clusters adsorbed along the unfolded protein chain. The interaction is enhanced with ionic strength only in the case of site-specific binding of an anionic surfactant with an anionic protein, whereas it is almost unchanged for other complexes of cationic and nonionic surfactants with anionic proteins. Interestingly, the interaction of BSA protein with ionic surfactants is significantly suppressed in the presence of nonionic surfactant. These results with mixed surfactants thus can be used to fold back the unfolded protein as well as to prevent surfactant-induced protein unfolding. For different solution conditions, the results are interpreted in terms of a change in fractal dimension, the overall size of the protein-surfactant complex, and the number of micelles attached to the protein. The interplay of electrostatic and hydrophobic interactions is found to govern the resultant structure of complexes.

  15. Tuning of protein-surfactant interaction to modify the resultant structure

    NASA Astrophysics Data System (ADS)

    Mehan, Sumit; Aswal, Vinod K.; Kohlbrecher, Joachim

    2015-09-01

    Small-angle neutron scattering and dynamic light scattering studies have been carried out to examine the interaction of bovine serum albumin (BSA) protein with different surfactants under varying solution conditions. We show that the interaction of anionic BSA protein (p H 7 ) with surfactant and the resultant structure are strongly modified by the charge head group of the surfactant, ionic strength of the solution, and mixed surfactants. The protein-surfactant interaction is maximum when two components are oppositely charged, followed by components being similarly charged through the site-specific binding, and no interaction in the case of a nonionic surfactant. This interaction of protein with ionic surfactants is characterized by the fractal structure representing a bead-necklace structure of micellelike clusters adsorbed along the unfolded protein chain. The interaction is enhanced with ionic strength only in the case of site-specific binding of an anionic surfactant with an anionic protein, whereas it is almost unchanged for other complexes of cationic and nonionic surfactants with anionic proteins. Interestingly, the interaction of BSA protein with ionic surfactants is significantly suppressed in the presence of nonionic surfactant. These results with mixed surfactants thus can be used to fold back the unfolded protein as well as to prevent surfactant-induced protein unfolding. For different solution conditions, the results are interpreted in terms of a change in fractal dimension, the overall size of the protein-surfactant complex, and the number of micelles attached to the protein. The interplay of electrostatic and hydrophobic interactions is found to govern the resultant structure of complexes.

  16. Modified Active Videogame Play Results in Moderate-Intensity Exercise.

    PubMed

    Monedero, Javier; McDonnell, Adam C; Keoghan, Melissa; O'Gorman, Donal J

    2014-08-01

    Large proportions of the population do not meet current American College of Sports Medicine physical activity recommendations, and innovative approaches are required. Most active videogames do not require a significant amount of energy expenditure. The purpose of this study was to determine if modifying an active videogame increased exercise intensity to meet current physical activity recommendations. After completing a maximal oxygen uptake test, participants did a familiarization session on a separate day. Thirteen healthy participants 24.2±3.4 years of age played (1) a sedentary videogame, (2) an active videogame, and (3) a modified active videogame designed to increase physical activity for 46 minutes in a randomized order on separate days. Oxygen uptake, heart rate, heart rate reserve, percentage of maximal heart rate, metabolic equivalents of task, and energy expenditure were significantly higher during the modified active videogame trial than during the active videogame or sedentary videogame trials and also between the active videogame and sedentary videogame. A simple modification to an existing active videogame was sufficient to reach moderate exercise intensity. Active videogames could provide an important option for increasing daily physical activity and reducing sedentary time.

  17. Ramp and periodic dynamics across non-Ising critical points

    NASA Astrophysics Data System (ADS)

    Ghosh, Roopayan; Sen, Arnab; Sengupta, K.

    2018-01-01

    We study ramp and periodic dynamics of ultracold bosons in an one-dimensional (1D) optical lattice which supports quantum critical points separating a uniform and a Z3 or Z4 symmetry broken density-wave ground state. Our protocol involves both linear and periodic drives which takes the system from the uniform state to the quantum critical point (for linear drive protocol) or to the ordered state and back (for periodic drive protocols) via controlled variation of a parameter of the system Hamiltonian. We provide exact numerical computation, for finite-size boson chains with L ≤24 using exact diagonalization (ED), of the excitation density D , the wave function overlap F , and the excess energy Q at the end of the drive protocol. For the linear ramp protocol, we identify the range of ramp speeds for which D and Q show Kibble-Zurek scaling. We find, based on numerical analysis with L ≤24 , that such scaling is consistent with that expected from critical exponents of the q -state Potts universality class with q =3 ,4 . For the periodic protocol, we show that the model displays near-perfect dynamical freezing at specific frequencies; at these frequencies D ,Q →0 and |F |→1 . We provide a semi-analytic explanation of such freezing behavior and relate this phenomenon to a many-body version of Stuckelberg interference. We suggest experiments which can test our theory.

  18. Safety performance functions for ramp terminals at diamond interchanges.

    DOT National Transportation Integrated Search

    2011-07-01

    This report documents two efforts to support CDOT in the area of Safety Performance Function (SPF) : development. The first involved the data collection and development of SPFs for five categories of ramp : terminals at diamond interchanges. For each...

  19. Guidelines for the design and placement of curb ramps.

    DOT National Transportation Integrated Search

    1982-01-01

    Information was obtained through surveys of ten state departments of transportation, four large U. S. cities, and eighteen departments of public works in Virginia. A sample inventory of curb ramps was made in 15 municipalities in Virginia. Interviews...

  20. [Prediction and influence factors of the ramp's noise of the entrance or exit of garages].

    PubMed

    Di, Guo-Qing; Zhang, Bang-Jun

    2005-09-01

    Some typical entrances/exits of the underground garages are chosen in urban residential areas. On the basis of the optimization of the positions of the noise sampling points and the groupings of the synchronous sampling points, by means of the acoustical analysis of the noise samples, the relation of the correlative factors, among the ramps' noise of the entrances or exits of the garages, the structure, grade, shape of the ramps, upgrade and downgrade, is studied. The prediction model of the ramp's noise influence of the entrance or exit of the garage is established through amending the noise influence of the entrance or exit of the even concrete road.

  1. 32. Underside of tracks showing columns, concreteencased Ibeams, and ramps ...

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

    32. Underside of tracks showing columns, concrete-encased I-beams, and ramps near storage room. Looking southwest. - Stillwell Avenue Station, Intersection of Stillwell & Surf Avenues, Brooklyn, Kings County, NY

  2. RAMP: a computer system for mapping regional areas

    Treesearch

    Bradley B. Nickey

    1975-01-01

    Until 1972, the U.S. Forest Service's Individual Fire Reports recorded locations by the section-township-range system..These earlier fire reports, therefore, lacked congruent locations. RAMP (Regional Area Mapping Procedure) was designed to make the reports more useful for quantitative analysis. This computer-based technique converts locations expressed in...

  3. M2-F2 on ramp

    NASA Image and Video Library

    1966-02-24

    The M2-F2 Lifting Body is seen here on the ramp at the NASA Dryden Flight Research Center. The success of Dryden's M2-F1 program led to NASA's development and construction of two heavyweight lifting bodies based on studies at NASA's Ames and Langley research centers -- the M2-F2 and the HL-10, both built by the Northrop Corporation. The "M" refers to "manned" and "F" refers to "flight" version. "HL" comes from "horizontal landing" and 10 is for the tenth lifting body model to be investigated by Langley. The first flight of the M2-F2 -- which looked much like the "F1" -- was on July 12, 1966. Milt Thompson was the pilot. By then, the same B-52 used to air launch the famed X-15 rocket research aircraft was modified to also carry the lifting bodies. Thompson was dropped from the B-52's wing pylon mount at an altitude of 45,000 feet on that maiden glide flight. The M2-F2 weighed 4,620 pounds, was 22 feet long, and had a width of about 10 feet. On May 10, 1967, during the sixteenth glide flight leading up to powered flight, a landing accident severely damaged the vehicle and seriously injured the NASA pilot, Bruce Peterson. NASA pilots and researchers realized the M2-F2 had lateral control problems, even though it had a stability augmentation control system. When the M2-F2 was rebuilt at Dryden and redesignated the M2-F3, it was modified with an additional third vertical fin -- centered between the tip fins -- to improve control characteristics. The M2-F2/F3 was the first of the heavy-weight, entry-configuration lifting bodies. Its successful development as a research test vehicle answered many of the generic questions about these vehicles. NASA donated the M2-F3 vehicle to the Smithsonian Institute in December 1973. It is currently hanging in the Air and Space Museum along with the X-15 aircraft number 1, which was its hangar partner at Dryden from 1965 to 1969.

  4. Evaluation of Pushback Decision-Support Tool Concept for Charlotte Douglas International Airport Ramp Operations

    NASA Technical Reports Server (NTRS)

    Hayashi, Miwa; Hoang, Ty; Jung, Yoon C.; Malik, Waqar; Lee, Hanbong; Dulchinos, Victoria L.

    2015-01-01

    This paper proposes a new departure pushback decision-support tool (DST) for airport ramp-tower controllers. It is based on NASA's Spot and Runway Departure Advisor (SARDA) collaborative decision-making concept, except with the modification that the gate releases now are controlled by tactical pushback (or gate-hold) advisories instead of strategic pre-assignments of target pushback times to individual departure flights. The proposed ramp DST relies on data exchange with the airport traffic control tower (ATCT) to coordinate pushbacks with the ATCT's flow-management intentions under current operational constraints, such as Traffic Management Initiative constraints. Airlines would benefit in reduced taxi delay and fuel burn. The concept was evaluated in a human-in-the-loop simulation experiment with current ramp-tower controllers at the Charlotte Douglas International Airport as participants. The results showed that the tool helped reduce taxi time by one minute per flight and overall departure flight fuel consumption by 10-12% without reducing runway throughput. Expect Departure Clearance Time (EDCT) conformance also was improved when advisories were provided. These benefits were attained without increasing the ramp-tower controllers' workload. Additionally, the advisories reduced the ATCT controllers' workload.

  5. Enhancing Power System Operational Flexibility With Flexible Ramping Products: A Review

    DOE PAGES

    Wang, Qin; Hodge, Bri-Mathias

    2016-12-09

    With the increased variability and uncertainty of net load induced from high penetrations of renewable energy resources and more flexible interchange schedules, power systems are facing great operational challenges in maintaining balance. Among these, the scarcity of ramp capability is an important culprit of power balance violations and high scarcity prices. To address this issue, market-based flexible ramping products (FRPs) have been proposed in the industry to improve the availability of ramp capacity. This paper presents an in-depth review of the modeling and implementation of FRPs. The major motivation is that although FRPs are widely discussed in the literature, itmore » is still unclear to many how they can be incorporated into a co-optimization framework that includes energy and ancillary services. The concept and a definition of power system operational flexibility as well as the needs for FRPs are introduced. The industrial practices of implementing FRPs under different market structures are presented. Market operation issues and future research topics are also discussed. In conclusion, this paper can provide researchers and power engineers with further insights into the state of the art, technical barriers, and potential directions for FRPs.« less

  6. Folic acid-modified soy protein nanoparticles for enhanced targeting and inhibitory.

    PubMed

    Cheng, Xu; Wang, Xin; Cao, Zhipeng; Yao, Weijing; Wang, Jun; Tang, Rupei

    2017-02-01

    Soy protein isolate (SPI) was hydrolyzed by compound enzymes to give water soluble low molecular soy protein (SP). SP and folic acid (FA) modified SP was polymerized with N-3- acrylamidophenylboronic acid (APBA) monomer in aqueous solution to give SP nanoparticles (SP NPs) and FA modified nanoparticles (FA-SP NPs), respectively. These NPs display excellent stability in different conditions, and have a uniform spherical shape with a diameter around of 200nm. Doxorubicin (DOX) was then successfully loaded into SP and FA-SP NPs with a desirable loading content of 13.33% and 16.01%, respectively. The cellular uptake and cytotoxicity of DOX-loaded SP NPs and FA-SP NPs were investigated using the two-dimensional (2D) monolayer cell model and three-dimensional (3D) multicellular spheroids (MCs). In vivo, tumor accumulation and growth inhibitory were then examined using H22 tumor-bearing mice. All these results demonstrated that conjugation of FA can efficiently enhance SP-based NPs' tumor accumulation and antitumor effect. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. 3. Cement and Plaster Warehouse, north facade. Loading ramp on ...

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

    3. Cement and Plaster Warehouse, north facade. Loading ramp on the right. Utility building, intrusion, on the far right. - Curtis Wharf, Cement & Plaster Warehouse, O & Second Streets, Anacortes, Skagit County, WA

  8. West view, general; Station Building, covered ramp, and Street Car ...

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

    West view, general; Station Building, covered ramp, and Street Car Waiting House - North Philadelphia Station, 2900 North Broad Street, on northwest corner of Broad Street & Glenwood Avenue, Philadelphia, Philadelphia County, PA

  9. CE separation of proteins and yeasts dynamically modified by PEG pyrenebutanoate with fluorescence detection.

    PubMed

    Horká, Marie; Růzicka, Filip; Holá, Veronika; Slais, Karel

    2007-07-01

    The optimized protocols of the bioanalytes separation, proteins and yeasts, dynamically modified by the nonionogenic tenside PEG pyrenebutanoate, were applied in CZE and CIEF with the acidic gradient in pH range 2-5.5, both with fluorescence detection. PEG pyrenebutanoate was used as a buffer additive for a dynamic modification of proteins and/or yeast samples. The narrow peaks of modified analytes were detected. The values of the pI's of the labeled proteins were calculated using new fluorescent pI markers in CIEF and they were found to be comparable with pI's of the native compounds. As an example of the possible use of the suggested CIEF technique, the mixed cultures of yeasts, Candida albicans, Candida glabrata, Candida kefyr, Candida krusei, Candida lusitaniae, Candida parapsilosis, Candida tropicalis, Candida zeylanoides, Geotrichum candidum, Saccharomyces cerevisiae, Trichosporon asahii and Yarrowia lipolytica, were reproducibly focused and separated with high sensitivity. Using UV excitation for the on-column fluorometric detection, the minimum detectable amounts of analytes, femtograms of proteins and down to ten cells injected on the separation capillary, were estimated.

  10. Building Ramps and Hovercrafts and Improving Math Skills.

    ERIC Educational Resources Information Center

    Bottge, Brian A.

    2001-01-01

    This article describes a video- and computer-based program used to motivate and develop mathematics skills in middle school students with disabilities. The program emphasizes real-life problems such as building a cage for a pet, a skate boarding ramp, and a "hovercraft" frame. Case studies illustrate the program's effectiveness with individual…

  11. Dual-mode fluorophore-doped nickel nitrilotriacetic acid-modified silica nanoparticles combine histidine-tagged protein purification with site-specific fluorophore labeling.

    PubMed

    Kim, Sung Hoon; Jeyakumar, M; Katzenellenbogen, John A

    2007-10-31

    We present the first example of a fluorophore-doped nickel chelate surface-modified silica nanoparticle that functions in a dual mode, combining histidine-tagged protein purification with site-specific fluorophore labeling. Tetramethylrhodamine (TMR)-doped silica nanoparticles, estimated to contain 700-900 TMRs per ca. 23 nm particle, were surface modified with nitrilotriacetic acid (NTA), producing TMR-SiO2-NTA-Ni2+. Silica-embedded TMR retains very high quantum yield, is resistant to quenching by buffer components, and is modestly quenched and only to a certain depth (ca. 2 nm) by surface-attached Ni2+. When exposed to a bacterial lysate containing estrogen receptor alpha ligand binding domain (ERalpha) as a minor component, these beads showed very high specificity binding, enabling protein purification in one step. The capacity and specificity of these beads for binding a his-tagged protein were characterized by electrophoresis, radiometric counting, and MALDI-TOF MS. ERalpha, bound to TMR-SiO2-NTA-Ni++ beads in a site-specific manner, exhibited good activity for ligand binding and for ligand-induced binding to coactivators in solution FRET experiments and protein microarray fluorometric and FRET assays. This dual-mode type TMR-SiO2-NTA-Ni2+ system represents a powerful combination of one-step histidine-tagged protein purification and site-specific labeling with multiple fluorophore species.

  12. From miracle fruit to transgenic tomato: mass production of the taste-modifying protein miraculin in transgenic plants.

    PubMed

    Hiwasa-Tanase, Kyoko; Hirai, Tadayoshi; Kato, Kazuhisa; Duhita, Narendra; Ezura, Hiroshi

    2012-03-01

    The utility of plants as biofactories has progressed in recent years. Some recombinant plant-derived pharmaceutical products have already reached the marketplace. However, with the exception of drugs and vaccines, a strong effort has not yet been made to bring recombinant products to market, as cost-effectiveness is critically important for commercialization. Sweet-tasting proteins and taste-modifying proteins have a great deal of potential in industry as substitutes for sugars and as artificial sweeteners. The taste-modifying protein, miraculin, functions to change the perception of a sour taste to a sweet one. This taste-modifying function can potentially be used not only as a low-calorie sweetener but also as a new seasoning that could be the basis of a new dietary lifestyle. However, miraculin is far from inexpensive, and its potential as a marketable product has not yet been fully developed. For the last several years, biotechnological production of this taste-modifying protein has progressed extensively. In this review, the characteristics of miraculin and recent advances in its production using transgenic plants are summarized, focusing on such topics as the suitability of plant species as expression hosts, the cultivation method for transgenic plants, the method of purifying miraculin and future advances required to achieve industrial use.

  13. 30. Underside of tracks showing columns, concreteencased Ibeams, and ramps ...

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

    30. Underside of tracks showing columns, concrete-encased I-beams, and ramps near token booths at street level. Looking southeast. - Stillwell Avenue Station, Intersection of Stillwell & Surf Avenues, Brooklyn, Kings County, NY

  14. North rear, east part. Ramp leads to basement utility rooms ...

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

    North rear, east part. Ramp leads to basement utility rooms and specimen preparation rooms. - San Bernardino Valley College, Life Science Building, 701 South Mount Vernon Avenue, San Bernardino, San Bernardino County, CA

  15. Experimental investigation of the micro-ramp based shock wave and turbulent boundary layer interaction control

    NASA Astrophysics Data System (ADS)

    Bo, Wang; Weidong, Liu; Yuxin, Zhao; Xiaoqiang, Fan; Chao, Wang

    2012-05-01

    Using a nanoparticle-based planar laser-scattering technique and supersonic particle image velocimetry, we investigated the effects of micro-ramp control on incident shockwave and boundary-layer interaction (SWBLI) in a low-noise supersonic wind-tunnel with Mach number 2.7 and Reynolds number Rθ = 5845. High spatiotemporal resolution wake structures downstream of the micro-ramps were detected, while a complex evolution process containing a streamwise counter-rotating vortex pair and large-scale hairpin-like vortices with Strouhal number Stδ of about 0.5-0.65 was revealed. The large-scale structures could survive while passing through the SWBLI region. Reflected shockwaves are clearly seen to be distorted accompanied by high-frequency fluctuations. Micro-ramp applications have a distinct influence on flow patterns of the SWBLI field that vary depending on spanwise locations. Both the shock foot and separation line exhibit undulations corresponding with modifications of the velocity distribution of the incoming boundary layer. Moreover, by energizing parts of the boundary flow, the micro-ramp is able to dampen the separation.

  16. San Antonio relay ramp: Area of stratal continuity between large-displacement barrier faults of the Edwards aquifer and Balcones fault zone, central Texas

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

    Collins, E.W.

    1996-09-01

    The San Antonio relay ramp, a gentle southwest-dipping monocline, formed between the tips of two en echelon master faults having maximum throws of >240 in. Structural analysis of this relay ramp is important to studies of Edwards aquifer recharge and ground-water flow because the ramp is an area of relatively good stratal continuity linking the outcrop belt recharge zone and unconfined aquifer with the downdip confined aquifer. Part of the relay ramp lies within the aquifer recharge zone and is crossed by several southeast-draining creeks, including Salado, Cibolo, and Comal Creeks, that supply water to the ramp recharge area. Thismore » feature is an analog for similar structures within the aquifer and for potential targets for hydrocarbons in other Gulf Coast areas. Defining the ramp is an {approximately}13-km-wide right step of the Edwards Group outcrop belt and the en echelon master faults that bound the ramp. The master faults strike N55-75{degrees}E, and maximum displacement exceeds the {approximately}165-m thickness of the Edwards Group strata. The faults therefore probably serve as barriers to Edwards ground-water flow. Within the ramp, tilted strata gently dip southwestward at {approximately}5 m/km, and the total structural relief along the ramp`s southwest-trending axis is <240 in. The ramp`s internal framework is defined by three fault blocks that are {approximately}4 to {approximately}6 km wide and are bound by northeast-striking faults having maximum throws between 30 and 150 m. Within the fault blocks, local areas of high fracture permeability may exist where smaller faults and joints are well connected.« less

  17. Effects of controlled element dynamics on human feedforward behavior in ramp-tracking tasks.

    PubMed

    Laurense, Vincent A; Pool, Daan M; Damveld, Herman J; van Paassen, Marinus René M; Mulder, Max

    2015-02-01

    In real-life manual control tasks, human controllers are often required to follow a visible and predictable reference signal, enabling them to use feedforward control actions in conjunction with feedback actions that compensate for errors. Little is known about human control behavior in these situations. This paper investigates how humans adapt their feedforward control dynamics to the controlled element dynamics in a combined ramp-tracking and disturbance-rejection task. A human-in-the-loop experiment is performed with a pursuit display and vehicle-like controlled elements, ranging from a single integrator through second-order systems with a break frequency at either 3, 2, or 1 rad/s, to a double integrator. Because the potential benefits of feedforward control increase with steeper ramp segments in the target signal, three steepness levels are tested to investigate their possible effect on feedforward control with the various controlled elements. Analyses with four novel models of the operator, fitted to time-domain data, reveal feedforward control for all tested controlled elements and both (nonzero) tested levels of ramp steepness. For the range of controlled element dynamics investigated, it is found that humans adapt to these dynamics in their feedforward response, with a close to perfect inversion of the controlled element dynamics. No significant effects of ramp steepness on the feedforward model parameters are found.

  18. Gas turbine power plant with supersonic shock compression ramps

    DOEpatents

    Lawlor, Shawn P [Bellevue, WA; Novaresi, Mark A [San Diego, CA; Cornelius, Charles C [Kirkland, WA

    2008-10-14

    A gas turbine engine. The engine is based on the use of a gas turbine driven rotor having a compression ramp traveling at a local supersonic inlet velocity (based on the combination of inlet gas velocity and tangential speed of the ramp) which compresses inlet gas against a stationary sidewall. The supersonic compressor efficiently achieves high compression ratios while utilizing a compact, stabilized gasdynamic flow path. Operated at supersonic speeds, the inlet stabilizes an oblique/normal shock system in the gasdynamic flow path formed between the rim of the rotor, the strakes, and a stationary external housing. Part load efficiency is enhanced by use of a lean pre-mix system, a pre-swirl compressor, and a bypass stream to bleed a portion of the gas after passing through the pre-swirl compressor to the combustion gas outlet. Use of a stationary low NOx combustor provides excellent emissions results.

  19. Characterization of p-phenylenediamine-albumin binding sites and T-cell responses to hapten-modified protein.

    PubMed

    Jenkinson, Claire; Jenkins, Rosalind E; Aleksic, Maja; Pirmohamed, Munir; Naisbitt, Dean J; Park, B Kevin

    2010-03-01

    Exposure to p-phenylenediamine (PPD) is associated with the development of T-cell-mediated allergic contact dermatitis. The purpose of this study was to define the nature of the interaction of PPD with the protein and the antigenic determinant that stimulates T cells. Mass spectrometry was employed to show that PPD oxidation products bind irreversibly to cysteine (Cys, position 34) in human serum albumin (HSA). A modified tryptic peptide was characterized with an increase in mass of 106 Da, corresponding to the addition of PPD and not to the secondary products of self conjugation. Lymphocytes from 10 PPD-allergic patients, but not tolerant/naive individuals, were stimulated with PPD and PPD-modified HSA. A total of 70 PPD-specific and 10 PPD-HSA-specific CD4+, CD8+, and CD4+CD8+, Th2-secreting T-cell clones were generated from three allergic patients. In total, 40 clones were stimulated with both PPD and PPD-modified HSA. PPD-modified HSA triggered T-cell responses through a classical hapten mechanism involving processing. Presentation of PPD to several clones was dependent on protein complex formation (42 out of 48) and processing (32 out of 68); however, 12% of clones were triggered with PPD directly. These data identify Cys as the single target for PPD-HSA binding, and show that PPD protein adducts are antigenic determinants in patients with contact dermatitis.

  20. Quantitative Protein Sulfenic Acid Analysis Identifies Platelet Releasate-Induced Activation of Integrin β2 on Monocytes via NADPH Oxidase.

    PubMed

    Li, Ru; Klockenbusch, Cordula; Lin, Liwen; Jiang, Honghui; Lin, Shujun; Kast, Juergen

    2016-12-02

    Physiological stimuli such as thrombin, or pathological stimuli such as lysophosphatidic acid (LPA), activate platelets. The activated platelets bind to monocytes through P-selectin-PSGL-1 interactions but also release the contents of their granules, commonly called "platelet releasate". It is known that monocytes in contact with platelet releasate produce reactive oxygen species (ROS). Reversible cysteine oxidation by ROS is considered to be a potential regulator of protein function. In a previous study, we used THP-1 monocytic cells exposed to LPA- or thrombin-induced platelet releasate and a modified biotin switch assay to unravel the biological processes that are influenced by reversible cysteine oxidation. To gain a better understanding of the redox regulation of monocytes in atherosclerosis, we have now altered the modified biotin switch to selectively quantify protein sulfenic acid, a subpopulation of reversible cysteine oxidation. Using arsenite as reducing agent in the modified biotin switch assay, we were able to quantify 1161 proteins, in which more than 100 sulfenic acid sites were identified. Bioinformatics analysis of the quantified sulfenic acid sites highlighted the relevant, previously missed biological process of monocyte transendothelial migration, which included integrin β 2 . Flow cytometry validated the activation of LFA-1 (α L β 2 ) and Mac-1 (α M β 2 ), two subfamilies of integrin β 2 complexes, on human primary monocytes following platelet releasate treatment. The activation of LFA-1 was mediated by ROS from NADPH oxidase (NOX) activation. Production of ROS and activation of LFA-1 in human primary monocytes were independent of P-selectin-PSGL-1 interaction. Our results proved the modified biotin switch assay to be a powerful tool with the ability to reveal new regulatory mechanisms and identify new therapeutic targets.

  1. Mapping Protein Surface Accessibility via an Electron Transfer Dissociation Selectively Cleavable Hydrazone Probe*

    PubMed Central

    Vasicek, Lisa; O'Brien, John P.; Browning, Karen S.; Tao, Zhihua; Liu, Hung-Wen; Brodbelt, Jennifer S.

    2012-01-01

    A protein's surface influences its role in protein-protein interactions and protein-ligand binding. Mass spectrometry can be used to give low resolution structural information about protein surfaces and conformations when used in combination with derivatization methods that target surface accessible amino acid residues. However, pinpointing the resulting modified peptides upon enzymatic digestion of the surface-modified protein is challenging because of the complexity of the peptide mixture and low abundance of modified peptides. Here a novel hydrazone reagent (NN) is presented that allows facile identification of all modified surface residues through a preferential cleavage upon activation by electron transfer dissociation coupled with a collision activation scan to pinpoint the modified residue in the peptide sequence. Using this approach, the correlation between percent reactivity and surface accessibility is demonstrated for two biologically active proteins, wheat eIF4E and PARP-1 Domain C. PMID:22393264

  2. Pure rotation of a prism on a ramp

    PubMed Central

    Zhao, Zhen; Liu, Caishan; Ma, Daolin

    2014-01-01

    In this work, we study a prism with a cross section in polygon rolling on a ramp inclined at a small angle. The prism under gravity rolls purely around each individual edge, intermittently interrupted by a sequence of face collisions between the side face of the prism and the ramp. By limiting the prism in a planar motion, we propose a mathematical model to deal with the events of the impacts. With a pair of laser-Doppler vibrometers, experiments are also conducted to measure the motions of various prisms made of different materials and with different edge number. Not only are good agreements achieved between our numerical and experimental results, but also an intriguing physical phenomenon is discovered: the purely rolling motion is nearly independent of the prism's materials, yet it is closely related to the prism's geometry. Imagine that an ideal circular section can be approximately equivalent to a polygon with a large enough edge number N, the finding presented in this paper may help discover the physical mechanism of rolling friction. PMID:25197242

  3. Pure rotation of a prism on a ramp.

    PubMed

    Zhao, Zhen; Liu, Caishan; Ma, Daolin

    2014-09-08

    In this work, we study a prism with a cross section in polygon rolling on a ramp inclined at a small angle. The prism under gravity rolls purely around each individual edge, intermittently interrupted by a sequence of face collisions between the side face of the prism and the ramp. By limiting the prism in a planar motion, we propose a mathematical model to deal with the events of the impacts. With a pair of laser-Doppler vibrometers, experiments are also conducted to measure the motions of various prisms made of different materials and with different edge number. Not only are good agreements achieved between our numerical and experimental results, but also an intriguing physical phenomenon is discovered: the purely rolling motion is nearly independent of the prism's materials, yet it is closely related to the prism's geometry. Imagine that an ideal circular section can be approximately equivalent to a polygon with a large enough edge number N , the finding presented in this paper may help discover the physical mechanism of rolling friction.

  4. Protein and energy evaluation of soybean meals processed from genetically modified high-protein soybeans.

    PubMed

    Edwards, H M; Douglas, M W; Parsons, C M; Baker, D H

    2000-04-01

    A conventional and two genetically modified soybean samples were processed to dehulled soybean meal (SBM) at a pilot plant and were compared with SBM from a commercial processing plant. Crude protein levels (%) of the experimental SBM samples were M700, 52.5; M702, 53.4; and M703, 62.7. The commercial SBM sample (UI) contained 47.5% protein. Amino acid, gross energy, lipid, and fiber analyses were carried out, and true metabolizable energy and true amino acid digestibility were determined with adult cecectomized cockerels. Digestible Lys, Met, Cys, Thr, and Val, and also TMEn, were higher (P < 0.05) and NDF, fat, and phospholipids were lower in M703 than in the other SBM samples. The results of this study indicate that M703 has considerable advantages over conventional SBM as a feed ingredient for broiler chickens.

  5. The Role of Histone Protein Modifications and Mutations in Histone Modifiers in Pediatric B-Cell Progenitor Acute Lymphoblastic Leukemia

    PubMed Central

    Janczar, Szymon; Janczar, Karolina; Pastorczak, Agata; Harb, Hani; Paige, Adam J. W.; Zalewska-Szewczyk, Beata; Danilewicz, Marian; Mlynarski, Wojciech

    2017-01-01

    While cancer has been long recognized as a disease of the genome, the importance of epigenetic mechanisms in neoplasia was acknowledged more recently. The most active epigenetic marks are DNA methylation and histone protein modifications and they are involved in basic biological phenomena in every cell. Their role in tumorigenesis is stressed by recent unbiased large-scale studies providing evidence that several epigenetic modifiers are recurrently mutated or frequently dysregulated in multiple cancers. The interest in epigenetic marks is especially due to the fact that they are potentially reversible and thus druggable. In B-cell progenitor acute lymphoblastic leukemia (BCP-ALL) there is a relative paucity of reports on the role of histone protein modifications (acetylation, methylation, phosphorylation) as compared to acute myeloid leukemia, T-cell ALL, or other hematologic cancers, and in this setting chromatin modifications are relatively less well studied and reviewed than DNA methylation. In this paper, we discuss the biomarker associations and evidence for a driver role of dysregulated global and loci-specific histone marks, as well as mutations in epigenetic modifiers in BCP-ALL. Examples of chromatin modifiers recurrently mutated/disrupted in BCP-ALL and associated with disease outcomes include MLL1, CREBBP, NSD2, and SETD2. Altered histone marks and histone modifiers and readers may play a particular role in disease chemoresistance and relapse. We also suggest that epigenetic regulation of B-cell differentiation may have parallel roles in leukemogenesis. PMID:28054944

  6. Linked Production of Pyroglutamate-Modified Proteins via Self-Cleavage of Fusion Tags with TEV Protease and Autonomous N-Terminal Cyclization with Glutaminyl Cyclase In Vivo

    PubMed Central

    Shih, Yan-Ping; Chou, Chi-Chi; Chen, Yi-Ling; Huang, Kai-Fa; Wang, Andrew H.- J.

    2014-01-01

    Overproduction of N-terminal pyroglutamate (pGlu)-modified proteins utilizing Escherichia coli or eukaryotic cells is a challenging work owing to the fact that the recombinant proteins need to be recovered by proteolytic removal of fusion tags to expose the N-terminal glutaminyl or glutamyl residue, which is then converted into pGlu catalyzed by the enzyme glutaminyl cyclase. Herein we describe a new method for production of N-terminal pGlu-containing proteins in vivo via intracellular self-cleavage of fusion tags by tobacco etch virus (TEV) protease and then immediate N-terminal cyclization of passenger target proteins by a bacterial glutaminyl cyclase. To combine with the sticky-end PCR cloning strategy, this design allows the gene of target proteins to be efficiently inserted into the expression vector using two unique cloning sites (i.e., SnaB I and Xho I), and the soluble and N-terminal pGlu-containing proteins are then produced in vivo. Our method has been successfully applied to the production of pGlu-modified enhanced green fluorescence protein and monocyte chemoattractant proteins. This design will facilitate the production of protein drugs and drug target proteins that possess an N-terminal pGlu residue required for their physiological activities. PMID:24733552

  7. 4. Threequarter view of Asylum (Western) Avenue viaduct and ramp ...

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

    4. Three-quarter view of Asylum (Western) Avenue viaduct and ramp on southeast corner of bridge, facing northwest. - Asylum Avenue Viaduct, Spanning Second Creek & Southern Railroad at State Route 62, Knoxville, Knox County, TN

  8. South view; Interior view of covered ramp to Street Car ...

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

    South view; Interior view of covered ramp to Street Car Waiting House from Station Building - North Philadelphia Station, 2900 North Broad Street, on northwest corner of Broad Street & Glenwood Avenue, Philadelphia, Philadelphia County, PA

  9. North view; Interior view of covered ramp to Station Building ...

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

    North view; Interior view of covered ramp to Station Building from Street Car Waiting House - North Philadelphia Station, 2900 North Broad Street, on northwest corner of Broad Street & Glenwood Avenue, Philadelphia, Philadelphia County, PA

  10. West view, general; Station Building, covered ramp, and Street Car ...

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

    West view, general; Station Building, covered ramp, and Street Car Waiting House, right to left - North Philadelphia Station, 2900 North Broad Street, on northwest corner of Broad Street & Glenwood Avenue, Philadelphia, Philadelphia County, PA

  11. An Evaluation of detectable warning surfaces for sidewalk curb ramps.

    DOT National Transportation Integrated Search

    1995-01-01

    The 1991 Americans with Disabilities Act Accessibility Guidelines required the installation of a detectable warning surface (raised truncated domes) on sidewalk curb ramps to alert visually impaired people to potential hazards. Although this requirem...

  12. Facility S 372, replacement dolphins and ramp from upper deck ...

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

    Facility S 372, replacement dolphins and ramp from upper deck of ferry boat (YFB 87). - U.S. Naval Base, Pearl Harbor, Ferry Landing Type, Halawa Landing on Ford Island, Pearl City, Honolulu County, HI

  13. Computational allergenicity prediction of transgenic proteins expressed in genetically modified crops.

    PubMed

    Verma, Alok Kumar; Misra, Amita; Subash, Swarna; Das, Mukul; Dwivedi, Premendra D

    2011-09-01

    Development of genetically modified (GM) crops is on increase to improve food quality, increase harvest yields, and reduce the dependency on chemical pesticides. Before their release in marketplace, they should be scrutinized for their safety. Several guidelines of different regulatory agencies like ILSI, WHO Codex, OECD, and so on for allergenicity evaluation of transgenics are available and sequence homology analysis is the first test to determine the allergenic potential of inserted proteins. Therefore, to test and validate, 312 allergenic, 100 non-allergenic, and 48 inserted proteins were assessed for sequence similarity using 8-mer, 80-mer, and full FASTA search. On performing sequence homology studies, ~94% the allergenic proteins gave exact matches for 8-mer and 80-mer homology. However, 20 allergenic proteins showed non-allergenic behavior. Out of 100 non-allergenic proteins, seven qualified as allergens. None of the inserted proteins demonstrated allergenic behavior. In order to improve the predictability, proteins showing anomalous behavior were tested by Algpred and ADFS separately. Use of Algpred and ADFS softwares reduced the tendency of false prediction to a great extent (74-78%). In conclusion, routine sequence homology needs to be coupled with some other bioinformatic method like ADFS/Algpred to reduce false allergenicity prediction of novel proteins.

  14. What Do Kinematic Models Imply About the Constitutive Properties of Rocks Deformed in Flat-Ramp-Flat Folds?

    NASA Astrophysics Data System (ADS)

    Cruz, L.; Nevitt, J. M.; Seixas, G.; Hilley, G. E.

    2017-10-01

    Kinematic theories of flat-ramp-flat folds relate fault angles to stratal dips in a way that allows prediction of structural geometries in areas of economic or scientific interest. However, these geometric descriptions imply constitutive properties of rocks that might be discordant with field and laboratory measurements. In this study, we compare deformation resulting from kinematic and mechanical models of flat-ramp-flat folds with identical geometries to determine the conditions over which kinematic models may be reasonably applied to folded rocks. Results show that most mechanical models do not conform to the geometries predicted by the kinematic models, and only low basal friction (μ ≤ 0.1) and shallow ramps (ramp angle ≤10°) produce geometries consistent with kinematic predictions. This implies that the kinematic models might be appropriate for a narrow set of geometric and basal fault friction parameters.

  15. Measuring effectiveness of ramp metering strategies on I-12.

    DOT National Transportation Integrated Search

    2011-05-01

    The main goal of this research is to conduct an overall assessment of the effectiveness of the newly implemented ramp metering strategy on I-12 in the Baton Rouge area. The research objectives of this study are to: 1. Conduct a brief literature revie...

  16. Orion Service Module Reaction Control System Plume Impingement Analysis Using PLIMP/RAMP2

    NASA Technical Reports Server (NTRS)

    Wang, Xiao-Yen J.; Gati, Frank; Yuko, James R.; Motil, Brian J.; Lumpkin, Forrest E.

    2009-01-01

    The Orion Crew Exploration Vehicle Service Module Reaction Control System engine plume impingement was computed using the plume impingement program (PLIMP). PLIMP uses the plume solution from RAMP2, which is the refined version of the reacting and multiphase program (RAMP) code. The heating rate and pressure (force and moment) on surfaces or components of the Service Module were computed. The RAMP2 solution of the flow field inside the engine and the plume was compared with those computed using GASP, a computational fluid dynamics code, showing reasonable agreement. The computed heating rate and pressure using PLIMP were compared with the Reaction Control System plume model (RPM) solution and the plume impingement dynamics (PIDYN) solution. RPM uses the GASP-based plume solution, whereas PIDYN uses the SCARF plume solution. Three sets of the heating rate and pressure solutions agree well. Further thermal analysis on the avionic ring of the Service Module showed that thermal protection is necessary because of significant heating from the plume.

  17. Cortical Activation Patterns Evoked by Temporally Asymmetric Sounds and Their Modulation by Learning

    PubMed Central

    Horikawa, Junsei

    2017-01-01

    When complex sounds are reversed in time, the original and reversed versions are perceived differently in spectral and temporal dimensions despite their identical duration and long-term spectrum-power profiles. Spatiotemporal activation patterns evoked by temporally asymmetric sound pairs demonstrate how the temporal envelope determines the readout of the spectrum. We examined the patterns of activation evoked by a temporally asymmetric sound pair in the primary auditory field (AI) of anesthetized guinea pigs and determined how discrimination training modified these patterns. Optical imaging using a voltage-sensitive dye revealed that a forward ramped-down natural sound (F) consistently evoked much stronger responses than its time-reversed, ramped-up counterpart (revF). The spatiotemporal maximum peak (maxP) of F-evoked activation was always greater than that of revF-evoked activation, and these maxPs were significantly separated within the AI. Although discrimination training did not affect the absolute magnitude of these maxPs, the revF-to-F ratio of the activation peaks calculated at the location where hemispheres were maximally activated (i.e., F-evoked maxP) was significantly smaller in the trained group. The F-evoked activation propagated across the AI along the temporal axis to the ventroanterior belt field (VA), with the local activation peak within the VA being significantly larger in the trained than in the naïve group. These results suggest that the innate network is more responsive to natural sounds of ramped-down envelopes than their time-reversed, unnatural sounds. The VA belt field activation might play an important role in emotional learning of sounds through its connections with amygdala. PMID:28451640

  18. Maize Seed Chitinase is Modified by a Protein Secreted by Bipolaris zeicola

    USDA-ARS?s Scientific Manuscript database

    Plants contain defense mechanisms that prevent infection by most fungi. Some specialized fungi have the ability to overcome plant defenses. The Zea mays (maize) seed chitinase ChitA has been previously reported as an antifungal protein. Here we report that ChitA is converted to a modified form by...

  19. 15. FIGUEROA STREET NORTHBOUND EXIT RAMP UNDER SOUTHBOUND LANES. UPPER ...

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

    15. FIGUEROA STREET NORTHBOUND EXIT RAMP UNDER SOUTHBOUND LANES. UPPER LEVEL IS INTERSTATE 1-5. LOOKING 162° SSE. - Arroyo Seco Parkway, Figueroa Street Viaduct, Spanning Los Angeles River, Los Angeles, Los Angeles County, CA

  20. Using archived ITS data to measure the operational benefits of a system-wide adaptive ramp metering system.

    DOT National Transportation Integrated Search

    2008-12-01

    A System-Wide Adaptive Ramp Metering (SWARM) system has been implemented in the Portland, Oregon metropolitan area, replacing the previous pre-timed ramp-metering system that had been in operation since 1981. SWARM has been deployed on six major corr...

  1. Modified C-reactive protein is expressed by stroke neovessels and is a potent activator of angiogenesis in vitro.

    PubMed

    Slevin, Mark; Matou-Nasri, Sabine; Turu, Marta; Luque, Ana; Rovira, Norma; Badimon, Lina; Boluda, Susana; Potempa, Lawrence; Sanfeliu, Coral; de Vera, Nuria; Krupinski, Jerzy

    2010-01-01

    Native C-reactive protein (nCRP) is a pentameric oligo-protein and an acute phase reactant whose serum expression is increased in patients with inflammatory disease. We have identified by immunohistochemistry, significant expression of a tissue-binding insoluble modified version or monomeric form of CRP (mCRP) associated with angiogenic microvessels in peri-infarcted regions of patients studied with acute ischaemic stroke. mCRP, but not nCRP was expressed in the cytoplasm and nucleus of damaged neurons. mCRP co-localized with CD105, a marker of angiogenesis in regions of revascularisation. In vitro investigations demonstrated that mCRP was preferentially expressed in human brain microvessel endothelial cells following oxygen-glucose deprivation and mCRP (but not column purified nCRP) associated with the endothelial cell surface, and was angiogenic to vascular endothelial cells, stimulating migration and tube formation in matrigel more strongly than fibroblast growth factor-2. The mechanism of signal transduction was not through the CD16 receptor. Western blotting showed that mCRP stimulated phosphorylation of the key down-stream mitogenic signalling protein ERK1/2. Pharmacological inhibition of ERK1/2 phosphorylation blocked the angiogenic effects of mCRP. We propose that mCRP may contribute to the neovascularization process and because of its abundant presence, be important in modulating angiogenesis in both acute stroke and later during neuro-recovery.

  2. HIstome--a relational knowledgebase of human histone proteins and histone modifying enzymes.

    PubMed

    Khare, Satyajeet P; Habib, Farhat; Sharma, Rahul; Gadewal, Nikhil; Gupta, Sanjay; Galande, Sanjeev

    2012-01-01

    Histones are abundant nuclear proteins that are essential for the packaging of eukaryotic DNA into chromosomes. Different histone variants, in combination with their modification 'code', control regulation of gene expression in diverse cellular processes. Several enzymes that catalyze the addition and removal of multiple histone modifications have been discovered in the past decade, enabling investigations of their role(s) in normal cellular processes and diverse pathological conditions. This sudden influx of data, however, has resulted in need of an updated knowledgebase that compiles, organizes and presents curated scientific information to the user in an easily accessible format. Here, we present HIstome, a browsable, manually curated, relational database that provides information about human histone proteins, their sites of modifications, variants and modifying enzymes. HIstome is a knowledgebase of 55 human histone proteins, 106 distinct sites of their post-translational modifications (PTMs) and 152 histone-modifying enzymes. Entries have been grouped into 5 types of histones, 8 types of post-translational modifications and 14 types of enzymes that catalyze addition and removal of these modifications. The resource will be useful for epigeneticists, pharmacologists and clinicians. HIstome: The Histone Infobase is available online at http://www.iiserpune.ac.in/∼coee/histome/ and http://www.actrec.gov.in/histome/.

  3. Comparison of energy and protein intakes of older people consuming a texture modified diet with a normal hospital diet.

    PubMed

    Wright, L; Cotter, D; Hickson, M; Frost, G

    2005-06-01

    There are very few studies looking at the energy and protein requirements of patients requiring texture modified diets. Dysphagia is the main indication for people to be recommended texture-modified diets. Older people post-stroke are the key group in the hospital setting who consume this type of diet. The diets can be of several consistencies ranging from pureed to soft textures. To compare the 24-hour dietary intake of older people consuming a texture modified diet in a clinical setting to older people consuming a normal hospital diet. Weighed food intakes and food record charts were used to quantify the patients' intakes, which were compared to their individual requirements. The oral intake of 55 patients was measured. Twenty-five of the patients surveyed were eating a normal diet and acted as controls for 30 patients who were prescribed a texture-modified diet. The results showed that the texture-modified group had significantly lower intakes of energy (3877 versus 6115 kJ, P < 0.0001) and protein (40 versus 60 g, P < 0.003) compared to consumption of the normal diet. The energy and protein deficit from estimated requirements was significantly greater in the texture-modified group (2549 versus 357 kJ, P < 0.0001; 6 versus 22 g, P = 0.013; respectively). These statistically significant results indicate that older people on texture-modified diets have a lower intake of energy and protein than those consuming a normal hospital diet and it is likely that other nutrients will be inadequate. All patients on texture-modified diets should be assessed by the dietitian for nutritional support. Evidence based strategies for improving overall nutrient intake should be identified.

  4. Line Operations Safety Assessments (LOSA) in Maintenance and Ramp Environments

    DOT National Transportation Integrated Search

    2017-01-01

    Data-driven modifications to risk management are needed in maintenance and ramp environments to assist the Federal Aviation Administration (FAA) in the development of adequate tools/systems that increase safety by aiding the identification of hazards...

  5. 97. VIEW OF PIER EXTENSION WITH RAMP IN FOREGROUND AND ...

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

    97. VIEW OF PIER EXTENSION WITH RAMP IN FOREGROUND AND 4TH TEE IN BACKGROUND, LOOKING SOUTHWEST FROM 3RD TEE - Huntington Beach Municipal Pier, Pacific Coast Highway at Main Street, Huntington Beach, Orange County, CA

  6. New laparoscopic procedure for left-sided pancreatic cancer-artery-first approach laparoscopic RAMPS using 3D technique.

    PubMed

    Yamamoto, Michihiro; Zaima, Masazumi; Yamamoto, Hidekazu; Harada, Hideki; Kawamura, Junichiro; Yamada, Masahiro; Yazawa, Tekefumi; Kawasoe, Junya

    2017-12-02

    For left-sided pancreatic ductal adenocarcinoma (PDAC), radical antegrade modular pancreatosplenectomy (RAMPS) is a reasonable surgical approach for tumor-free margin resection and systemic lymph node clearance. In pancreaticoduodenectomy for PDAC, the superior mesenteric artery (SMA)-first approach (or the "artery-first approach") has become the standard procedure. With improvements in laparoscopic instruments and techniques, some surgeons attempted to apply laparoscopic RAMPS (L-RAMPS) for carefully selected patients with left-sided PDAC. However, owing to several technical difficulties in this procedure, its application remains uncommon. Moreover, the artery-first approach in L-RAMPS has not been reported. Here, we developed the artery-first approach L-RAMPS for left-sided PDAC and have presented the same in this report. Between June 2014 and July 2015, 16 patients with left-sided PDAC were referred to our division for pancreatic resection. The following technique was used for performing L-RAMPS on 3 of the 16 patients (19%). Six trocars were placed. After opening the omental bursa, only the middle segment of the pancreas was initially separated from both the left renal vein and the SMA. We termed this procedure as the "artery-first approach using a dome-shaped dorsomedial dissection (3D) technique." This 3D technique enabled the interruption of the entire arterial supply to the specimen while preserving the venous drainage through the splenic vein for preventing venous congestion. The technique also contributed to the early detection of no tumor infiltration into the SMA and the early determination of posterior dissection plane. After pancreatic neck transection, the splenic artery and vein were divided. Finally, the pancreatic tail and spleen were dissected in a right-to-left direction. All operations were completed without any intraoperative complications. The median blood loss and retrieved lymph node count were 75 mL and 37, respectively, which were

  7. Modelling controlled VDE's and ramp-down scenarios in ITER

    NASA Astrophysics Data System (ADS)

    Lodestro, L. L.; Kolesnikov, R. A.; Meyer, W. H.; Pearlstein, L. D.; Humphreys, D. A.; Walker, M. L.

    2011-10-01

    Following the design reviews of recent years, the ITER poloidal-field coil-set design, including in-vessel coils (VS3), and the divertor configuration have settled down. The divertor and its material composition (the latter has not been finalized) affect the development of fiducial equilibria and scenarios together with the coils through constraints on strike-point locations and limits on the PF and control systems. Previously we have reported on our studies simulating controlled vertical events in ITER with the JCT 2001 controller to which we added a PID VS3 circuit. In this paper we report and compare controlled VDE results using an optimized integrated VS and shape controller in the updated configuration. We also present our recent simulations of alternate ramp-down scenarios, looking at the effects of ramp-down time and shape strategies, using these controllers. This work performed under the auspices of the U.S. Department of Energy by LLNL under Contract DE-AC52-07NA27344.

  8. High-protein diet differently modifies intestinal goblet cell characteristics and mucosal cytokine expression in ileum and colon.

    PubMed

    Lan, Annaïg; Andriamihaja, Mireille; Blouin, Jean-Marc; Liu, Xinxin; Descatoire, Véronique; Desclée de Maredsous, Caroline; Davila, Anne-Marie; Walker, Francine; Tomé, Daniel; Blachier, François

    2015-01-01

    We have previously shown that high-protein (HP) diet ingestion causes marked changes in the luminal environment of the colonic epithelium. This study aimed to evaluate the impact of such modifications on small intestinal and colonic mucosa, two segments with different transit time and physiological functions. Rats were fed with either normal protein (NP; 14% protein) or HP (53% protein) isocaloric diet for 2 weeks, and parameters related to intestinal mucous-secreting cells and to several innate/adaptive immune characteristics (myeloperoxidase activity, cytokine and epithelial TLR expression, proportion of immune cells in gut-associated lymphoid tissues) were measured in the ileum and colon. In ileum from HP animals, we observed hyperplasia of mucus-producing cells concomitant with an increased expression of Muc2 at both gene and protein levels, reduction of mucosal myeloperoxidase activity, down-regulation of Tlr4 gene expression in enterocytes and down-regulation of mucosal Th cytokines associated with CD4+ lymphocyte reduction in mesenteric lymph nodes. These changes coincided with an increased amount of acetate in the ileal luminal content. In colon, HP diet ingestion resulted in a lower number of goblet cells at the epithelial surface but increased goblet cell number in colonic crypts together with an increased Muc3 and a slight reduction of Il-6 gene expression. Our data suggest that HP diet modifies the goblet cell distribution in colon and, in ileum, increases goblet cell activity and decreases parameters related to basal gut inflammatory status. The impact of HP diet on intestinal mucosa in terms of beneficial or deleterious effects is discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Structure function analysis of two-scale Scalar Ramps. Part II: Coherent structure scaling and surface renewal applications

    USDA-ARS?s Scientific Manuscript database

    Structure functions are used to study the dissipation and inertial range scales of turbulent energy, to parameterize remote turbulence measurements, and to characterize ramp features in the turbulent field. The ramp features are associated with turbulent coherent structures, which dominate energy a...

  10. North side, showing ramp at western section but photograph taken ...

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

    North side, showing ramp at western section but photograph taken to east of CO-172-BR-8 and looking southwesterly. - Fitzsimons General Hospital, Infirmary, Northwest Corner of East Bushnell Avenue & South Page Street, Aurora, Adams County, CO

  11. Acute stressor exposure modifies plasma exosome-associated heat shock protein 72 (Hsp72) and microRNA (miR-142-5p and miR-203).

    PubMed

    Beninson, Lida A; Brown, Peter N; Loughridge, Alice B; Saludes, Jonel P; Maslanik, Thomas; Hills, Abigail K; Woodworth, Tyler; Craig, Wendy; Yin, Hang; Fleshner, Monika

    2014-01-01

    Exosomes, biologically active nanoparticles (40-100 nm) released by hematopoietic and non-hematopoietic cells, contain a variety of proteins and small, non-coding RNA known as microRNA (miRNA). Exposure to various pathogens and disease states modifies the composition and function of exosomes, but there are no studies examining in vivo exosomal changes evoked by the acute stress response. The present study reveals that exposing male Fisher 344 rats to an acute stressor modulates the protein and miRNA profile of circulating plasma exosomes, specifically increasing surface heat shock protein 72 (Hsp72) and decreasing miR-142-5p and -203. The selected miRNAs and Hsp72 are associated with immunomodulatory functions and are likely a critical component of stress-evoked modulation of immunity. Further, we demonstrate that some of these stress-induced modifications in plasma exosomes are mediated by sympathetic nervous system (SNS) activation of alpha-1 adrenergic receptors (ADRs), since drug-mediated blockade of the receptors significantly attenuates the stress-induced modifications of exosomal Hsp72 and miR-142-5p. Together, these findings demonstrate that activation of the acute stress response modifies the proteomic and miRNA profile of exosomes released into the circulation.

  12. Chromatographic and traditional albumin isotherms on cellulose: a model for wound protein adsorption on modified cotton

    USDA-ARS?s Scientific Manuscript database

    Albumin is the most abundant protein found in healing wounds. Traditional and chromatogrpahic protein isotherms of albumin binding on modified cotton fibers are useful in understanding albumin binding to cellulose wound dressings. An important consideration in the design of cellulosic wound dressin...

  13. Oral immunization of Carassius auratus with modified recombinant A-layer proteins entrapped in alginate beads.

    PubMed

    Maurice, Sarah; Nussinovitch, Amos; Jaffe, Nicole; Shoseyov, Oded; Gertler, Arieh

    2004-12-09

    This study was focused on the utilization of a recombinant expression system to produce a unique modified subunit vaccine possessing a self-contained delivery system which could potentially improve the uptake and delivery of vaccine products as well their immunogenic potential. For this purpose the A-layer protein (At-R) associated with the fish pathogen atypical Aeromonas salmonicida was cloned and modified by the genetic fusion of the protein transduction domain (MTS) derived from Kaposi fibroblast growth factor (At-MTS). The potential for these proteins to be employed as antigens for oral immunization of goldfish was examined by encapsulation of At-R, At-MTS and the control, BSA, into biodegradable alginate gel macrospheres which were fed to goldfish in place of standard pellet fish feed. The bead physical properties were modified only in the presence of At-R and the temporal release of proteins was significantly less when At-MTS was employed. Western blot analysis of serum samples collected from fish following intubation with the recombinant proteins determined that the rate of protein uptake from the digestive tract into the blood system improved considerably when MTS was fused to At-R. Experimental fish were fed one of three protein-alginate formulae on a schedule of 3 days/week or 5 days/month for a period of 2 months. After 1 month, animals fed on the 5-day protocol demonstrated increased serum antibody titers while following an additional month of feeding this level decreased and titers were found to be higher in fish maintained on the 3-day regime. Fish fed At-MTS maintained the highest titer at the end of 2-month period. To determine whether the diminished antibody titers were a result of oral tolerance fish were injected intraperitoneally with the At-R antigen. Only experimental groups which had been fed At-R or At-MTS demonstrated increased antibody titers which paralleled a typical secondary humoral response. In spite of the presence of an increased

  14. TRANSP-based Trajectory Optimization of the Current Profile Evolution to Facilitate Robust Non-inductive Ramp-up in NSTX-U

    NASA Astrophysics Data System (ADS)

    Wehner, William; Schuster, Eugenio; Poli, Francesca

    2016-10-01

    Initial progress towards the design of non-inductive current ramp-up scenarios in the National Spherical Torus Experiment Upgrade (NSTX-U) has been made through the use of TRANSP predictive simulations. The strategy involves, first, ramping the plasma current with high harmonic fast waves (HHFW) to about 400 kA, and then further ramping to 900 kA with neutral beam injection (NBI). However, the early ramping of neutral beams and application of HHFW leads to an undesirably peaked current profile making the plasma unstable to ballooning modes. We present an optimization-based control approach to improve on the non-inductive ramp-up strategy. We combine the TRANSP code with an optimization algorithm based on sequential quadratic programming to search for time evolutions of the NBI powers, the HHFW powers, and the line averaged density that define an open-loop actuator strategy that maximizes the non-inductive current while satisfying constraints associated with the current profile evolution for MHD stable plasmas. This technique has the potential of playing a critical role in achieving robustly stable non-inductive ramp-up, which will ultimately be necessary to demonstrate applicability of the spherical torus concept to larger devices without sufficient room for a central coil. Supported by the US DOE under the SCGSR Program.

  15. 8. REINFORCED CONCRETE SLAB ROOF FROM NORTHWEST EDGE, ACCESS RAMP ...

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

    8. REINFORCED CONCRETE SLAB ROOF FROM NORTHWEST EDGE, ACCESS RAMP IN FOREGROUND, VIEW TOWARDS SOUTHEAST. - Glenn L. Martin Company, Titan Missile Test Facilities, CaptiveTest Stand D-3, Waterton Canyon Road & Colorado Highway 121, Lakewood, Jefferson County, CO

  16. Facility 596, detail of ramp from below, with replacement sheetpile ...

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

    Facility 596, detail of ramp from below, with replacement sheet-pile dolphin on right and southernmost dolphins in background. - U.S. Naval Base, Pearl Harbor, Ferry Landing Type, Halawa Landing on Ford Island, Pearl City, Honolulu County, HI

  17. Kinematic analysis of the thoracic limb of healthy dogs during descending stair and ramp exercises.

    PubMed

    Kopec, Nadia L; Williams, Jane M; Tabor, Gillian F

    2018-01-01

    OBJECTIVE To compare the kinematics of the thoracic limb of healthy dogs during descent of stairs and a ramp with those during a trot across a flat surface (control). ANIMALS 8 privately owned dogs. PROCEDURES For each dog, the left thoracic limb was instrumented with 5 anatomic markers to facilitate collection of 2-D kinematic data during each of 3 exercises (descending stairs, descending a ramp, and trotting over a flat surface). The stair exercise consisted of 4 steps with a 35° slope. For the ramp exercise, a solid plank was placed over the steps to create a ramp with a 35° slope. For the flat exercise, dogs were trotted across a flat surface for 2 m. Mean peak extension, peak flexion, and range of movement (ROM) of the shoulder, elbow, and carpal joints were compared among the 3 exercises. RESULTS Mean ROM for the shoulder and elbow joints during the stair exercise were significantly greater than during the flat exercise. Mean peak extension of the elbow joint during the flat exercise was significantly greater than that during both the stair and ramp exercises. Mean peak flexion of the elbow joint during the stair exercise was significantly greater than that during the flat exercise. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that descending stairs may be beneficial for increasing the ROM of the shoulder and elbow joints of dogs. Descending stair exercises may increase elbow joint flexion, whereas flat exercises may be better for targeting elbow joint extension.

  18. Quantitative analysis of modified proteins and their positional isomers by tandem mass spectrometry: human histone H4.

    PubMed

    Pesavento, James J; Mizzen, Craig A; Kelleher, Neil L

    2006-07-01

    Here we show that fragment ion abundances from dissociation of ions created from mixtures of multiply modified histone H4 (11 kDa) or of N-terminal synthetic peptides (2 kDa) correspond to their respective intact ion abundances measured by Fourier transform mass spectrometry. Isomeric mixtures of modified forms of the same protein are resolved and quantitated with a precision of protein ions created by electrospray greatly easing many of the systematic biases that more strongly affect small peptides (e.g., differences in ionization efficiency and ion m/z values). The ion fragmentation methods validated here are directly extensible to intact human proteins to derive quantitative information on the highly related and often isomeric protein forms created by combinatorial arrays of posttranslational modifications.

  19. Validating the energy transport modeling of the DIII-D and EAST ramp up experiments using TSC

    NASA Astrophysics Data System (ADS)

    Liu, Li; Guo, Yong; Chan, Vincent; Mao, Shifeng; Wang, Yifeng; Pan, Chengkang; Luo, Zhengping; Zhao, Hailin; Ye, Minyou

    2017-06-01

    The confidence in ramp up scenario design of the China fusion engineering test reactor (CFETR) can be significantly enhanced using validated transport models to predict the current profile and temperature profile. In the tokamak simulation code (TSC), two semi-empirical energy transport models (the Coppi-Tang (CT) and BGB model) and three theory-based models (the GLF23, MMM95 and CDBM model) are investigated on the CFETR relevant ramp up discharges, including three DIII-D ITER-like ramp up discharges and one EAST ohmic discharge. For the DIII-D discharges, all the transport models yield dynamic {{\\ell}\\text{i}} within +/- 0.15 deviations except for some time points where the experimental fluctuation is very strong. All the models agree with the experimental {β\\text{p}} except that the CT model strongly overestimates {β\\text{p}} in the first half of ramp up phase. When applying the CT, CDBM and GLF23 model to estimate the internal flux, they show maximum deviations of more than 10% because of inaccuracies in the temperature profile predictions, while the BGB model performs best on the internal flux. Although all the models fall short in reproducing the dynamic {{\\ell}\\text{i}} evolution for the EAST tokamak, the result of the BGB model is the closest to the experimental {{\\ell}\\text{i}} . Based on these comparisons, we conclude that the BGB model is the most consistent among these models for simulating CFETR ohmic ramp-up. The CT model with improvement for better simulation of the temperature profiles in the first half of ramp up phase will also be attractive. For the MMM95, GLF23 and CDBM model, better prediction of the edge temperature will improve the confidence for CFETR L-mode simulation. Conclusive validation of any transport model will require extensive future investigation covering a larger variety discharges.

  20. Haploinsufficiency for Adrenomedullin Reduces Pinopodes and Diminishes Uterine Receptivity in Mice1

    PubMed Central

    Li, Manyu; Wu, Yongqin; Caron, Kathleen M.

    2008-01-01

    Adrenomedullin (AM) is a multifunctional peptide vasodilator that signals through a G-protein-coupled receptor when the receptor, called calcitonin receptor-like receptor (CL), is associated with a receptor activity-modifying protein 2 (RAMP2). We demonstrated previously that haploinsufficieny for each of these genes led to reduced maternal fertility, and that even a modest genetic reduction of AM peptide caused maternal defects in implantation, placentation, and fetal growth. Here, we further demonstrate that Adm+/− female mice displayed reduced pregnancy success rates that were not caused by defects in folliculogenesis, ovulation, or fertilization. The poor fertility of Adm+/− female mice could not be rescued by transfer of wild-type blastocysts, which suggested an underlying defect in uterine receptivity. In fact, we found that Adm, Calcrl, and Ramp2 gene expressions are tightly and spatiotemporally regulated in the luminal epithelial cells of the uterus during the estrus cycle and the peri-implantation period. RAMP3, which also generates an AM receptor when associated with CL, had a diametrically opposite expression pattern than that of Adm, Calcrl, and Ramp2 and was most robustly induced in the stroma of the uterus. Finally, we discovered that Adm+/− female mice have a substantially reduced number of pinopodes on the uterine luminal epithelial surface, which is indicative and possibly causative of the poor uterine receptivity. Taken together, our studies identify a new class of pharmacologically tractable proteins that are involved in establishing uterine receptivity through the regulation of pinopode formation. PMID:18716289

  1. Micro-Ramp Flow Control for Oblique Shock Interactions: Comparisons of Computational and Experimental Data

    NASA Technical Reports Server (NTRS)

    Hirt, Stephanie M.; Reich, David B.; O'Connor, Michael B.

    2012-01-01

    Computational fluid dynamics was used to study the effectiveness of micro-ramp vortex generators to control oblique shock boundary layer interactions. Simulations were based on experiments previously conducted in the 15- by 15-cm supersonic wind tunnel at the NASA Glenn Research Center. Four micro-ramp geometries were tested at Mach 2.0 varying the height, chord length, and spanwise spacing between micro-ramps. The overall flow field was examined. Additionally, key parameters such as boundary-layer displacement thickness, momentum thickness and incompressible shape factor were also examined. The computational results predicted the effects of the microramps well, including the trends for the impact that the devices had on the shock boundary layer interaction. However, computing the shock boundary layer interaction itself proved to be problematic since the calculations predicted more pronounced adverse effects on the boundary layer due to the shock than were seen in the experiment.

  2. Applied Distributed Model Predictive Control for Energy Efficient Buildings and Ramp Metering

    NASA Astrophysics Data System (ADS)

    Koehler, Sarah Muraoka

    suited for nonlinear optimization problems. The parallel computation of the algorithm exploits iterative linear algebra methods for the main linear algebra computations in the algorithm. We show that the splitting of the algorithm is flexible and can thus be applied to various distributed platform configurations. The two proposed algorithms are applied to two main energy and transportation control problems. The first application is energy efficient building control. Buildings represent 40% of energy consumption in the United States. Thus, it is significant to improve the energy efficiency of buildings. The goal is to minimize energy consumption subject to the physics of the building (e.g. heat transfer laws), the constraints of the actuators as well as the desired operating constraints (thermal comfort of the occupants), and heat load on the system. In this thesis, we describe the control systems of forced air building systems in practice. We discuss the "Trim and Respond" algorithm which is a distributed control algorithm that is used in practice, and show that it performs similarly to a one-step explicit DMPC algorithm. Then, we apply the novel distributed primal-dual active-set method and provide extensive numerical results for the building MPC problem. The second main application is the control of ramp metering signals to optimize traffic flow through a freeway system. This application is particularly important since urban congestion has more than doubled in the past few decades. The ramp metering problem is to maximize freeway throughput subject to freeway dynamics (derived from mass conservation), actuation constraints, freeway capacity constraints, and predicted traffic demand. In this thesis, we develop a hybrid model predictive controller for ramp metering that is guaranteed to be persistently feasible and stable. This contrasts to previous work on MPC for ramp metering where such guarantees are absent. We apply a smoothing method to the hybrid model predictive

  3. Flat-ramp vs. convex-concave thrust geometries in a deformable hanging wall: new insights from analogue modeling experiments

    NASA Astrophysics Data System (ADS)

    Almeida, Pedro; Tomas, Ricardo; Rosas, Filipe; Duarte, Joao; Terrinha, Pedro

    2015-04-01

    Different modes of strain accommodation affecting a deformable hanging-wall in a flat-ramp-flat thrust system were previously addressed through several (sandbox) analog modeling studies, focusing on the influence of different variables, such as: a) thrust ramp dip angle and friction (Bonini et al, 2000); b) prescribed thickness of the hanging-wall (Koy and Maillot, 2007); and c) sin-thrust erosion (compensating for topographic thrust edification, e.g. Persson and Sokoutis, 2002). In the present work we reproduce the same experimental procedure to investigate the influence of two different parameters on hanging-wall deformation: 1) the geometry of the thrusting surface; and 2) the absence of a velocity discontinuity (VD) that is always present in previous similar analogue modeling studies. Considering the first variable we use two end member ramp geometries, flat-ramp-flat and convex-concave, to understand the control exerted by the abrupt ramp edges in the hanging-wall stress-strain distribution, comparing the obtain results with the situation in which such edge singularities are absent (convex-concave thrust ramp). Considering the second investigated parameter, our motivation was the recognition that the VD found in the different analogue modeling settings simply does not exist in nature, despite the fact that it has a major influence on strain accommodation in the deformable hanging-wall. We thus eliminate such apparatus artifact from our models and compare the obtained results with the previous ones. Our preliminary results suggest that both investigated variables play a non-negligible role on the structural style characterizing the hanging-wall deformation of convergent tectonic settings were such thrust-ramp systems were recognized. Acknowledgments This work was sponsored by the Fundação para a Ciência e a Tecnologia (FCT) through project MODELINK EXPL/GEO-GEO/0714/2013. Pedro Almeida wants to thank to FCT for the Ph.D. grant (SFRH/BD/52556/2014) under the

  4. 20. INTERIOR VIEW TO THE EAST OF THE ACCESS RAMP ...

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

    20. INTERIOR VIEW TO THE EAST OF THE ACCESS RAMP TO THE HOT DISASSEMBLY AREA FROM THE COLD ASSEMBLY AREA. - Nevada Test Site, Reactor Maintenance Assembly & Dissassembly Facility, Area 25, Jackass Flats, Junction of Roads F & G, Mercury, Nye County, NV

  5. 10. REINFORCED CONCRETE SLAB ROOF FROM SOUTHEASTERN EDGE, ACCESS RAMPS ...

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

    10. REINFORCED CONCRETE SLAB ROOF FROM SOUTHEASTERN EDGE, ACCESS RAMPS AT LEFT AND RIGHT, VIEW TOWARDS NORTHWEST. - Glenn L. Martin Company, Titan Missile Test Facilities, Captive Test Stand D-1, Waterton Canyon Road & Colorado Highway 121, Lakewood, Jefferson County, CO

  6. Plasma current ramp-up by lower hybrid wave using innovative antennas on TST-2

    NASA Astrophysics Data System (ADS)

    Takase, Yuichi; Ejiri, Akira; Moeller, Charles; Roidl, Benedikt; Shinya, Takahiro; Tsujii, Naoto; Yajima, Satoru; Yamazaki, Hibiki; Kitayama, Akichika; Matsumoto, Naoki; Sato, Akito; Sonehara, Masateru; Takahashi, Wataru; Tajiri, Yoshiyuki; Takei, Yuki; Togashi, Hiro; Toida, Kazuya; Yoshida, Yusuke

    2016-10-01

    Non-inductive plasma current (Ip) ramp-up by RF power in the lower hybrid frequency range is being studied on the TST-2 spherical tokamak (R = 0.36 m, a = 0.23 m, Bt = 0.3 T, Ip = 0.1 MA). Up to 400 kW of RF power is available at a frequency of 200 MHz. An innovative antenna called the capacitively-coupled combline (CCC) antenna was developed to excite a sharp, highly directional traveling wave with the electric field polarized in the toroidal direction. It is an array of resonant circuit elements made of capacitance and inductance, coupled to neighboring elements by mutual capacitance. Two CCC antennas are installed in TST-2, a 13-element outboard-launch antenna and a 6-element top-launch antenna. The latter was installed in March 2016 to improve accessibility to the core and to achieve single-pass damping. The suspected wave power loss in the scrape-off layer plasma should also be avoided. Ip ramp-up to 25 kA has been achieved so far. An upgrade of the Bt power supply is planned to take advantage of the observed improvement of Ip ramp-up with Bt. Higher Bt for longer pulses should improve the Ip ramp-up efficiency by improving wave accessibility and by reducing prompt orbit losses of energetic electrons.

  7. Radar echo processing with partitioned de-ramp

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

    Dubbert, Dale F.; Tise, Bertice L.

    2013-03-19

    The spurious-free dynamic range of a wideband radar system is increased by apportioning de-ramp processing across analog and digital processing domains. A chirp rate offset is applied between the received waveform and the reference waveform that is used for downconversion to the intermediate frequency (IF) range. The chirp rate offset results in a residual chirp in the IF signal prior to digitization. After digitization, the residual IF chirp is removed with digital signal processing.

  8. B-47A on ramp

    NASA Technical Reports Server (NTRS)

    1953-01-01

    Boeing B-47A (NACA 150) shown on the ramp near NACA High-Speed Flight Research Station at South Base of Edwards Air Force Base, California, in 1953. The B-47A Stratojet's wing is mounted high on the fuselage with a sweep back of 36 degrees and a span of 116 feet, with wing vortex generators installed. A two engine pod under each wing, and an additional engine pod at each wing tip using General Electric J-47-GE-23 turbojets. The airplane is fitted with a nose boom for measuring airspeed, altitude, angle-of-attack and angle-of-sideslip, and an optigraph for measuring the movements of target lights on the wing and tail.

  9. Experimental studies on flow visualization and velocity field of compression ramp with different incoming boundary layers

    NASA Astrophysics Data System (ADS)

    Wu, Yu; Yi, Shi-He; He, Lin; Chen, Zhi; Zhu, Yang-Zhu

    2014-11-01

    Experimental studies which focus on flow visualization and the velocity field of a supersonic laminar/turbulent flow over a compression ramp were carried out in a Mach 3.0 wind tunnel. Fine flow structures and velocity field structures were obtained via NPLS (nanoparticle-tracer planar laser scattering) and PIV (particle image velocimetry) techniques, time-averaged flow structures were researched, and spatiotemporal evolutions of transient flow structures were analyzed. The flow visualization results indicated that when the ramp angles were 25°, a typical separation occurred in the laminar flow, some typical flow structures such as shock induced by the boundary layer, separation shock, reversed flow and reattachment shock were visible clearly. While a certain extent separation occurred in turbulent flow, the separation region was much smaller. When the ramp angles were 28°, laminar flow separated further, and the separation region expanded evidently, flow structures in the separation region were complex. While a typical separation occurred in turbulent flow, reversed flow structures were significant, flow structures in the separation region were relatively simple. The experimental results of velocity field were corresponding to flow visualization, and the velocity field structures of both compression ramp flows agreed with the flow structures well. There were three layered structures in the U component velocity, and the V component velocity appeared like an oblique “v”. Some differences between these two compression ramp flows can be observed in the velocity profiles of the shear layer and the shearing intensity.

  10. Orion Service Module Reaction Control System Plume Impingement Analysis Using PLIMP/RAMP2

    NASA Technical Reports Server (NTRS)

    Wang, Xiao-Yen; Lumpkin, Forrest E., III; Gati, Frank; Yuko, James R.; Motil, Brian J.

    2009-01-01

    The Orion Crew Exploration Vehicle Service Module Reaction Control System engine plume impingement was computed using the plume impingement program (PLIMP). PLIMP uses the plume solution from RAMP2, which is the refined version of the reacting and multiphase program (RAMP) code. The heating rate and pressure (force and moment) on surfaces or components of the Service Module were computed. The RAMP2 solution of the flow field inside the engine and the plume was compared with those computed using GASP, a computational fluid dynamics code, showing reasonable agreement. The computed heating rate and pressure using PLIMP were compared with the Reaction Control System plume model (RPM) solution and the plume impingement dynamics (PIDYN) solution. RPM uses the GASP-based plume solution, whereas PIDYN uses the SCARF plume solution. Three sets of the heating rate and pressure solutions agree well. Further thermal analysis on the avionic ring of the Service Module was performed using MSC Patran/Pthermal. The obtained temperature results showed that thermal protection is necessary because of significant heating from the plume.

  11. Improved mucoadhesion and cell uptake of chitosan and chitosan oligosaccharide surface-modified polymer nanoparticles for mucosal delivery of proteins.

    PubMed

    Dyawanapelly, Sathish; Koli, Uday; Dharamdasani, Vimisha; Jain, Ratnesh; Dandekar, Prajakta

    2016-08-01

    The main aim of the present study was to compare mucoadhesion and cellular uptake efficiency of chitosan (CS) and chitosan oligosaccharide (COS) surface-modified polymer nanoparticles (NPs) for mucosal delivery of proteins. We have developed poly (D, L-lactide-co-glycolide) (PLGA) NPs, surface-modified COS-PLGA NPs and CS-PLGA NPs, by using double emulsion solvent evaporation method, for encapsulating bovine serum albumin (BSA) as a model protein. Surface modification of NPs was confirmed using physicochemical characterization methods such as particle size and zeta potential, SEM, TEM and FTIR analysis. Both surface-modified PLGA NPs displayed a slow release of protein compared to PLGA NPs. Furthermore, we have explored the mucoadhesive property of COS as a material for modifying the surface of polymeric NPs. During in vitro mucoadhesion test, positively charged COS-PLGA NPs and CS-PLGA NPs exhibited enhanced mucoadhesion, compared to negatively charged PLGA NPs. This interaction was anticipated to improve the cell interaction and uptake of NPs, which is an important requirement for mucosal delivery of proteins. All nanoformulations were found to be safe for cellular delivery when evaluated in A549 cells. Moreover, intracellular uptake behaviour of FITC-BSA loaded NPs was extensively investigated by confocal laser scanning microscopy and flow cytometry. As we hypothesized, positively charged COS-PLGA NPs and CS-PLGA NPs displayed enhanced intracellular uptake compared to negatively charged PLGA NPs. Our results demonstrated that CS- and COS-modified polymer NPs could be promising carriers for proteins, drugs and nucleic acids via nasal, oral, buccal, ocular and vaginal mucosal routes.

  12. 9 CFR 313.1 - Livestock pens, driveways and ramps.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...) Livestock pens, driveways and ramps shall be maintained in good repair. They shall be free from sharp or... acceptable construction and maintenance. (c) U.S. Suspects (as defined in § 301.2(xxx)) and dying, diseased... awaiting disposition by the inspector. (d) Livestock pens and driveways shall be so arranged that sharp...

  13. EBR-II high-ramp transients under computer control

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

    Forrester, R.J.; Larson, H.A.; Christensen, L.J.

    1983-01-01

    During reactor run 122, EBR-II was subjected to 13 computer-controlled overpower transients at ramps of 4 MWt/s to qualify the facility and fuel for transient testing of LMFBR oxide fuels as part of the EBR-II operational-reliability-testing (ORT) program. A computer-controlled automatic control-rod drive system (ACRDS), designed by EBR-II personnel, permitted automatic control on demand power during the transients.

  14. Mixed Linear/Square-Root Encoded Single-Slope Ramp Provides Low-Noise ADC with High Linearity for Focal Plane Arrays

    NASA Technical Reports Server (NTRS)

    Wrigley, Chris J.; Hancock, Bruce R.; Newton, Kenneth W.; Cunningham, Thomas J.

    2013-01-01

    Single-slope analog-to-digital converters (ADCs) are particularly useful for onchip digitization in focal plane arrays (FPAs) because of their inherent monotonicity, relative simplicity, and efficiency for column-parallel applications, but they are comparatively slow. Squareroot encoding can allow the number of code values to be reduced without loss of signal-to-noise ratio (SNR) by keeping the quantization noise just below the signal shot noise. This encoding can be implemented directly by using a quadratic ramp. The reduction in the number of code values can substantially increase the quantization speed. However, in an FPA, the fixed pattern noise (FPN) limits the use of small quantization steps at low signal levels. If the zero-point is adjusted so that the lowest column is onscale, the other columns, including those at the center of the distribution, will be pushed up the ramp where the quantization noise is higher. Additionally, the finite frequency response of the ramp buffer amplifier and the comparator distort the shape of the ramp, so that the effective ramp value at the time the comparator trips differs from the intended value, resulting in errors. Allowing increased settling time decreases the quantization speed, while increasing the bandwidth increases the noise. The FPN problem is solved by breaking the ramp into two portions, with some fraction of the available code values allocated to a linear ramp and the remainder to a quadratic ramp. To avoid large transients, both the value and the slope of the linear and quadratic portions should be equal where they join. The span of the linear portion must cover the minimum offset, but not necessarily the maximum, since the fraction of the pixels above the upper limit will still be correctly quantized, albeit with increased quantization noise. The required linear span, maximum signal and ratio of quantization noise to shot noise at high signal, along with the continuity requirement, determines the number of

  15. 40 CFR 174.505 - Bacillus thuringiensis modified Cry3A protein (mCry3A) in corn; exemption from the requirement of...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... protein (mCry3A) in corn; exemption from the requirement of a tolerance. 174.505 Section 174.505... thuringiensis modified Cry3A protein (mCry3A) in corn; exemption from the requirement of a tolerance. Residues of Bacillus thuringiensis modified Cry3A protein (mCry3A) in corn are exempt from the requirement of...

  16. 40 CFR 174.505 - Bacillus thuringiensis modified Cry3A protein (mCry3A) in corn; exemption from the requirement of...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... protein (mCry3A) in corn; exemption from the requirement of a tolerance. 174.505 Section 174.505... thuringiensis modified Cry3A protein (mCry3A) in corn; exemption from the requirement of a tolerance. Residues of Bacillus thuringiensis modified Cry3A protein (mCry3A) in corn are exempt from the requirement of...

  17. 40 CFR 174.505 - Bacillus thuringiensis modified Cry3A protein (mCry3A) in corn; exemption from the requirement of...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... protein (mCry3A) in corn; exemption from the requirement of a tolerance. 174.505 Section 174.505... thuringiensis modified Cry3A protein (mCry3A) in corn; exemption from the requirement of a tolerance. Residues of Bacillus thuringiensis modified Cry3A protein (mCry3A) in corn are exempt from the requirement of...

  18. 40 CFR 174.505 - Bacillus thuringiensis modified Cry3A protein (mCry3A) in corn; exemption from the requirement of...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... protein (mCry3A) in corn; exemption from the requirement of a tolerance. 174.505 Section 174.505... thuringiensis modified Cry3A protein (mCry3A) in corn; exemption from the requirement of a tolerance. Residues of Bacillus thuringiensis modified Cry3A protein (mCry3A) in corn are exempt from the requirement of...

  19. 40 CFR 174.505 - Bacillus thuringiensis modified Cry3A protein (mCry3A) in corn; exemption from the requirement of...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... protein (mCry3A) in corn; exemption from the requirement of a tolerance. 174.505 Section 174.505... thuringiensis modified Cry3A protein (mCry3A) in corn; exemption from the requirement of a tolerance. Residues of Bacillus thuringiensis modified Cry3A protein (mCry3A) in corn are exempt from the requirement of...

  20. Hartmann-Hahn 2D-map to optimize the RAMP-CPMAS NMR experiment for pharmaceutical materials.

    PubMed

    Suzuki, Kazuko; Martineau, Charlotte; Fink, Gerhard; Steuernagel, Stefan; Taulelle, Francis

    2012-02-01

    Cross polarization-magic angle spinning (CPMAS) is the most used experiment for solid-state NMR measurements in the pharmaceutical industry, with the well-known variant RAMP-CPMAS its dominant implementation. The experimental work presented in this contribution focuses on the entangled effects of the main parameters of such an experiment. The shape of the RAMP-CP pulse has been considered as well as the contact time duration, and a particular attention also has been devoted to the radio-frequency (RF) field inhomogeneity. (13)C CPMAS NMR spectra have been recorded with a systematic variation of (13)C and (1)H constant radiofrequency field pair values and represented as a Hartmann-Hahn matching two-dimensional map. Such a map yields a rational overview of the intricate optimal conditions necessary to achieve an efficient CP magnetization transfer. The map also highlights the effects of sweeping the RF by the RAMP-CP pulse on the number of Hartmann-Hahn matches crossed and how RF field inhomogeneity helps in increasing the CP efficiency by using a larger fraction of the sample. In the light of the results, strategies for optimal RAMP-CPMAS measurements are suggested, which lead to a much higher efficiency than constant amplitude CP experiment. Copyright © 2012 John Wiley & Sons, Ltd.

  1. Motor unit recruitment and EMG power spectra during ramp contractions of a bifunctional muscle.

    PubMed

    Dupont, L; Gamet, D; Pérot, C

    2000-08-01

    Surface electromyograms (EMGs) were analysed on the short and long head of the biceps brachii (BBSH and BBLH) during single (F and S) or dual (F+S) flexion and supination tasks. It was confirmed, by the analysis of EMG root-mean-square (RMS) values, that the highest activations of BBSH and BBLH were obtained during a maximal dual task. This study was essentially concerned with the analysis of power spectra data obtained during progressive or ramp contractions (RCs). The shape of the power spectra established during the first second of the RCs differs between F, S and F+S tasks. Differences in mean power frequency (MPF) calculated during RCs would be representative of a recruitment of motor units (MUs) that is, at least partly, task-dependent. In order to compare MPF values calculated from RCs performed under different mechanical conditions (F, S and F+S), MPF-RMS(PSD) relationships have been established (RMS(PSD) being defined as the power spectrum density RMS). Both BBSH and BBLH exhibited initial MPF values higher in supination RC than in flexion RC. Because of plateau values reached at the same level of muscle activation whatever the task performed, the slope of the MPF-RMS(PSD) relationship was lower in S than in F. These results are in favour of MU recruitment that is, at least partly, different in F and in S conditions. Dual submaximal tasks seem to mix the activation of the F and S subpopulations of MUs as revealed by the spectral parameters obtained during F+S ramp contractions. This study could find some implication in the field of muscle rehabilitation or reinforcement.

  2. Study on the antibacterial mechanism of copper ion- and neodymium ion-modified α-zirconium phosphate with better antibacterial activity and lower cytotoxicity.

    PubMed

    Cai, Xiang; Zhang, Bin; Liang, Yuanyuan; Zhang, Jinglin; Yan, Yinghui; Chen, Xiaoyin; Wu, Zhimin; Liu, Hongxi; Wen, Shuiping; Tan, Shaozao; Wu, Ting

    2015-08-01

    To improve the antibacterial activity of Cu(2+), a series of Cu(2+) and/or Nd(3+)-modified layered α-zirconium phosphate (ZrP) was prepared and characterized, and the antibacterial activities of the prepared Cu(2+) and/or Nd(3+)-modified ZrP on Gram-negative Escherichia coli were investigated. The results showed that the basal spacing of ZrP was not obviously affected by the incorporation of Cu(2+), but the basal spacing of the modified ZrP changed into an amorphous state with increasing additions of Nd(3+). An antibacterial mechanism showed that Cu(2+) and Nd(3+) could enter into E. coli cells, leading to changes in ion concentrations and leakage of DNA, RNA and protein. The Cu(2+)- and Nd(3+)-modified ZrP, combining the advantages of Cu(2+) and Nd(3+), displayed excellent additive antibacterial activity and lower cytotoxicity, suggesting the great potential application as an antibacterial powder for microbial control. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

  3. Effect of novel chitosan-fluoroaluminosilicate resin modified glass ionomer cement supplemented with translationally controlled tumor protein on pulp cells.

    PubMed

    Wanachottrakul, Nattaporn; Chotigeat, Wilaiwan; Kedjarune-Leggat, Ureporn

    2014-04-01

    Dental materials that can promote cell proliferation and function is required for regenerative pulp therapy. Resin modified glass ionomer cement (RMGIC), a broadly used liner or restorative material, can cause apoptosis to pulp cells mainly due to HEMA (2-hydroxyethyl methacrylate), the released residual monomer. Recent studies found that chitosan and albumin could promote release of protein in GIC while translationally controlled tumor protein (TCTP) has an anti-apoptotic activity against HEMA. The aim of this study was to examine the effect of chitosan and albumin modified RMGIC (Exp-RMGIC) supplemented with TCTP on pulp cell viability and mineralization. Exp-RMGIC+TCTP was composed of RMGIC powder incorporated with 15 % of chitosan, 5 % albumin and supplemented with TCTP mixed with the same liquid components of RMGIC. The effect of each specimen on pulp cells was examined using the Transwell plate. From the MTT assay, Exp-RMGIC+TCTP had the highest percentages of viable cells (P < 0.05) at both 24 and 74 h. Flow cytometry revealed that, after 24 h, Exp-RMGIC+TCTP gave the lowest percentages of apoptotic cells compared to other groups. There was no difference in alkaline phosphatase (ALP) activity among different formula of the specimens, while cells cultured in media with TCTP had higher ALP activity. Von Kossa staining revealed that RMGIC+TCTP, and Exp-RMGIC+TCTP had higher percentages of calcium deposit area compared to those without TCTP. It was concluded that Exp-RMGIC supplemented with TCTP had less cytotoxicity than RMGIC and can protect cells from apoptosis better than RMGIC supplemented with TCTP.

  4. Full-Scale Instrumented Testing and Analysis of Matting Systems for Airfield Parking Ramps and Taxiways

    DTIC Science & Technology

    2007-12-01

    system can only be precisely determined by examining all the materials used in the mat, their structure , orientation, dimensions, etc. and determining...ER D C/ G SL T R- 07 -3 3 Full-Scale Instrumented Testing and Analysis of Matting Systems for Airfield Parking Ramps and Taxiways Chad...ERDC/GSL TR-07-33 December 2007 Full-Scale Instrumented Testing and Analysis of Matting Systems for Airfield Parking Ramps and Taxiways Chad A

  5. Serum lipids modify periodontal infection - C-reactive protein association.

    PubMed

    Haro, Anniina; Saxlin, Tuomas; Suominen, Anna-Liisa; Ylöstalo, Pekka; Leiviskä, Jaana; Tervonen, Tellervo; Knuuttila, Matti

    2012-09-01

    To investigate whether low-grade inflammation-related factors such as serum low-density (LDL-C) and high-density lipoprotein cholesterol (HDL-C) modify the association between periodontal infection and C-reactive protein. This study was based on a subpopulation of the Health 2000 Survey, which consisted of dentate, non-diabetic, non-rheumatic subjects who were 30-49 years old (n = 2710). The extent of periodontal infection was measured by means of the number of teeth with periodontal pocket ≥4 mm and teeth with periodontal pocket ≥6 mm and systemic inflammation using high sensitive C-reactive protein. The extent of periodontal infection was associated with elevated levels of C-reactive protein among those subjects whose HDL-C value was below the median value of 1.3 mmol/l or LDL-C above the median value of 3.4 mmol/l. Among those with HDL-C ≥ 1.3 mmol/l or LDL-C ≤ 3.4 mmol/l, the association between periodontal infection and serum concentrations of C-reactive protein was practically non-existent. This study suggests that the relation of periodontal infection to the systemic inflammatory condition is more complicated than previously presumed. The findings of this study suggest that the possible systemic effect of periodontal infection is dependent on serum lipid composition. © 2012 John Wiley & Sons A/S.

  6. Exterior direct detail view of revised entry handicap ramp at ...

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

    Exterior direct detail view of revised entry handicap ramp at east side of Building 7 (including 3-story trash dump tower), looking north - North Beach Place, 431 Bay Street, 530 Francisco Street, 431 Bay Street, 530 Francisco Street, San Francisco, San Francisco County, CA

  7. North side, middle section, looking west at exterior ramp and ...

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

    North side, middle section, looking west at exterior ramp and enclosed corridor connecting buildings 511 and 515. East side of corridor. Building 516 is to the right. - Fitzsimons General Hospital, Infirmary, Northwest Corner of East Bushnell Avenue & South Page Street, Aurora, Adams County, CO

  8. Detail of staircase (stepped ramp) and retaining wall at West ...

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

    Detail of staircase (stepped ramp) and retaining wall at West 102nd Street, soccer field at right, looking south, with London Plane trees surrounding field. - Henry Hudson Parkway, Extending 11.2 miles from West 72nd Street to Bronx-Westchester border, New York County, NY

  9. Rice proteins, extracted by alkali and α-amylase, differently affect in vitro antioxidant activity.

    PubMed

    Wang, Zhengxuan; Liu, Ye; Li, Hui; Yang, Lin

    2016-09-01

    Alkali treatment and α-amylase degradation are different processes for rice protein (RP) isolation. The major aim of this study was to determine the influence of two different extraction methods on the antioxidant capacities of RPA, extracted by alkaline (0.2% NaOH), and RPE, extracted by α-amylase, during in vitro digestion for 2h with pepsin and for 3h with pancreatin. Upon pepsin-pancreatin digestion, the protein hydrolysates (RPA-S, RPE-S), which were the supernatants in the absence of undigested residue, and the whole protein digests (RPA, RPE), in which undigested residue remained, were measured. RPE exhibited the stronger antioxidant responses to free radical scavenging activity, metal chelating activity, and reducing power, whereas the weakest antioxidant capacities were produced by RPE-S. In contrast, no significant differences in antioxidant activity were observed between RPA and RPA-S. The present study demonstrated that the in vitro antioxidant responses induced by the hydrolysates and the protein digests of RPs could be affected differently by alkali treatment and α-amylase degradation, suggesting that the extraction is a vital processing step to modify the antioxidant capacities of RPs. The results of the current study indicated that the protein digests, in which undigested residues remained, could exhibit more efficacious antioxidant activity compared to the hydrolysates. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Small ubiquitin-related modifier is secreted and shows cytokine-like activity.

    PubMed

    Hosono, Hidetaka; Yokosawa, Hideyoshi

    2008-05-01

    Small ubiquitin-related modifier (SUMO) is a type I ubiquitin-like protein family member and is covalently attached to various target proteins. Through this post-translational modification, SUMO plays important roles in various cellular events. Here, we show that SUMO is secreted from cultured cells in an endoplasmic reticulum (ER)/Golgi-independent manner and that this secretion occurs without covalent binding to target proteins or chain formation. Overexpression experiments using C-terminally truncated mutants of SUMO revealed that the secretion requires the C-terminal sequence. Recombinant SUMO-3 protein was capable of binding to and promoting the proliferation of cultured cells. Thus, we propose that SUMO functions as a cytokine-like molecule extracellularly.

  11. Non-peptidic antagonists of the CGRP receptor, BIBN4096BS and MK-0974, interact with the calcitonin receptor-like receptor via methionine-42 and RAMP1 via tryptophan-74.

    PubMed

    Miller, Philip S; Barwell, James; Poyner, David R; Wigglesworth, Mark J; Garland, Stephen L; Donnelly, Dan

    2010-01-01

    The receptor for calcitonin gene-related peptide (CGRP) has been the target for the development of novel small molecule antagonists for the treatment of migraine. Two such antagonists, BIBN4096BS and MK-0974, have shown great promise in clinical trials and hence a deeper understanding of the mechanism of their interaction with the receptor is now required. The structure of the CGRP receptor is unusual since it is comprised of a hetero-oligomeric complex between the calcitonin receptor-like receptor (CRL) and an accessory protein (RAMP1). Both the CLR and RAMP1 components have extracellular domains which interact with each other and together form part of the peptide-binding site. It seems likely that the antagonist binding site will also be located on the extracellular domains and indeed Trp-74 of RAMP1 has been shown to form part of the binding site for BIBN4096BS. However, despite a chimeric study demonstrating the role of the N-terminal domain of CLR in antagonist binding, no specific residues have been identified. Here we carry out a mutagenic screen of the extreme N-terminal domain of CLR (residues 23-63) and identify a mutant, Met-42-Ala, which displays 48-fold lower affinity for BIBN4096BS and almost 900-fold lower affinity for MK-0974. In addition, we confirm that the Trp-74-Lys mutation at human RAMP1 reduces BIBN4096BS affinity by over 300-fold and show for the first time a similar effect for MK-0974 affinity. The data suggest that the non-peptide antagonists occupy a binding site close to the interface of the N-terminal domains of CLR and RAMP1. Copyright 2009 Elsevier Inc. All rights reserved.

  12. Geotechnical characterization of the North Ramp of the Exploratory Studies Facility: Yucca Mountain Site Characterization Project. Volume 2, NRG corehole data appendices

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

    Brechtel, C.E.; Lin, Ming; Martin, E.

    1995-05-01

    This report presents the results of the geological and geotechnical characterization of the Miocene volcanic tuff rocks of the Timber Mountain and Paintbrush groups that the tunnel boring machine will encounter during excavations of the Exploratory Studies Facility (ESF) North Ramp. The information in this report was developed to support the design of the ESF North Ramp. The ESF is being constructed by the DOE as part of the Yucca Mountain Project site characterization activities. The purpose of these activities is to evaluate the potential to locate the national high-level nuclear waste repository on land within and adjacent to themore » Nevada Test Site (NTS), Nye County, Nevada. This report was prepared as part of the Soil and Rock Properties Studies in accordance with the 8.3.1.14.2 Study Plan to Provide Soil and Rock Properties. This is volume 2 which contains NRG Corehole Data for each of the NRG Holes.« less

  13. A MODIFIED PROTEIN ASSAY FROM MICROGRAM TO LOW NANOGRAM LEVELS IN DILUTE SAMPLES

    PubMed Central

    Heda, Ghanshyam D.; Kunwar, Upasana; Heda, Rajiv P.

    2013-01-01

    In this paper we present a modified and improved protein assay that was previously described as ‘amidoschwarz assay’ by Schaffner and Weissmann (Anal. Biochem. 56, 1973, 502–514). Our improved protein assay is user-friendly and 30 to 40 times more sensitive than the earlier method. The assay was developed into 3 formats (maco, micro, and nanoassay) with TCA as protein precipitating agent; measuring up to 96 samples. The macro and micro formats of this assay require a single reagent staining with amido black of protein dots, bound to nitrocellulose membrane with lowest protein measurements to 1 μg and 0.1 μg respectively. The nanoassay on the other hand with combination staining of amido black followed by colloidal gold can extend the detection limit to 2.5 ng of protein. Protein concentrations were determined by densitometry and/or spectrophotometry. This assay is compatible with many ionic and non-ionic detergents. This improved protein assay provides an additional choice to researchers in measuring total protein concentration accurately in dilute biological samples as low as 0.125 μg/ml, prior to their biochemical analysis such as in comparative proteomics. PMID:24135655

  14. The Archival Appraisal of Photographs: A RAMP Study with Guidelines.

    ERIC Educational Resources Information Center

    Leary, William H.

    Prepared for Unesco's Records and Archives Management Programme (RAMP), this study is designed to provide archivists, manuscript and museum curators, and other interested information professionals in both industrialized and developing countries with an understanding of the archival character of photographs, and a set of guidelines for the…

  15. Turbidite carbon distribution by Ramped PyrOx, Astoria Canyon

    NASA Astrophysics Data System (ADS)

    Childress, L. B.; Galy, V.; McNichol, A. P.

    2017-12-01

    The magnitude and nature of carbon preserved in marine sediments can be affected by long-term processes such as climate change and tectonic transport; preservation of carbon can also be affected by short-term, episodic disturbances such as storm events, landslides, and earthquakes. In margins with active canyons, these systems can be efficient burial networks for carbon. The downslope displacement and reorganization of sediment and associated organic carbon (OC) during turbidite formation alters oxygen diffusion and the potential for aerobic oxidation, thereby modifying the redox geochemistry of the sediment package. Generally termed as a `burn-down', reactions at the subsurface oxidation front are linked to a loss of OC preservation within turbidite sequences. Still debated is the source of the OC residual within `burn-down' events, primarily whether the preserved material is dominated by terrestrial or marine components. To better understand the significance of canyon systems and turbidite deposits in the transport, preservation, and `burn-down' of organic carbon, samples from these systems can be studied using the Ramped PyrOx (RPO) technique. Whereas bulk radiocarbon measurements are unsuitable within turbidite deposits, RPO is well suited for characterizing the distribution of carbon sources within a turbidite interval. To complement RPO analyses, OC and N content, stable carbon isotope composition, gamma ray attenuation bulk density, computerized tomography, and magnetic susceptibility were determined. The turbidite systems of the Cascadia Subduction Zone have been extensively studied in relation to the Holocene paleoseismic record. Gravity cores collected in 2011 aboard the R/V Wecoma capture turbidite deposits in Astoria Canyon and demonstrate characteristics of `burn down' intervals. RPO data from within a 15 cm turbidite interval indicate minimal variation in reactivity structure, stable carbon isotope values and radiocarbon age, suggesting a shared

  16. AMP-activated protein kinase: Role in metabolism and therapeutic implications.

    PubMed

    Schimmack, Greg; Defronzo, Ralph A; Musi, Nicolas

    2006-11-01

    AMP-activated protein kinase (AMPK) is an enzyme that works as a fuel gauge which becomes activated in situations of energy consumption. AMPK functions to restore cellular ATP levels by modifying diverse metabolic and cellular pathways. In the skeletal muscle, AMPK is activated during exercise and is involved in contraction-stimulated glucose transport and fatty acid oxidation. In the heart, AMPK activity increases during ischaemia and functions to sustain ATP, cardiac function and myocardial viability. In the liver, AMPK inhibits the production of glucose, cholesterol and triglycerides and stimulates fatty acid oxidation. Recent studies have shown that AMPK is involved in the mechanism of action of metformin and thiazolidinediones, and the adipocytokines leptin and adiponectin. These data, along with evidence that pharmacological activation of AMPK in vivo improves blood glucose homeostasis, cholesterol concentrations and blood pressure in insulin-resistant rodents, make this enzyme an attractive pharmacological target for the treatment of type 2 diabetes, ischaemic heart disease and other metabolic diseases.

  17. Dynamics of the outgoing turbulent boundary layer in a Mach 5 unswept compression ramp interaction

    NASA Technical Reports Server (NTRS)

    Gramann, Richard A.; Dolling, David S.

    1990-01-01

    Wall pressure fluctuations have been measured under the unsteady separation shock and on the ramp face in an unswept Mach 5 compression ramp interaction. The freestream Reynolds number was 51.0 x 10 to the 6th/m, and the incoming turbulent boundary layer developed on the tunnel floor under approximately adiabatic wall temperature conditions. Standard data-acquisition methods, as well as real-time and posttest conditional sampling techniques were used. The results show that the mean and rms pressure levels are strong functions of separation shock position. At all stations on the ramp, from the corner to where the pressure reaches the theoretical inviscid value, the pressure signals have two dominant components: a low frequency component characteristic of the global unsteadiness, which correlates with the separation shock motion, and a higher frequency component associated with turbulence. The former is the major contributor to the overall signal variance.

  18. Effect of initial shock wave voltage on shock wave lithotripsy-induced lesion size during step-wise voltage ramping.

    PubMed

    Connors, Bret A; Evan, Andrew P; Blomgren, Philip M; Handa, Rajash K; Willis, Lynn R; Gao, Sujuan

    2009-01-01

    To determine if the starting voltage in a step-wise ramping protocol for extracorporeal shock wave lithotripsy (SWL) alters the size of the renal lesion caused by the SWs. To address this question, one kidney from 19 juvenile pigs (aged 7-8 weeks) was treated in an unmodified Dornier HM-3 lithotripter (Dornier Medical Systems, Kennesaw, GA, USA) with either 2000 SWs at 24 kV (standard clinical treatment, 120 SWs/min), 100 SWs at 18 kV followed by 2000 SWs at 24 kV or 100 SWs at 24 kV followed by 2000 SWs at 24 kV. The latter protocols included a 3-4 min interval, between the 100 SWs and the 2000 SWs, used to check the targeting of the focal zone. The kidneys were removed at the end of the experiment so that lesion size could be determined by sectioning the entire kidney and quantifying the amount of haemorrhage in each slice. The average parenchymal lesion for each pig was then determined and a group mean was calculated. Kidneys that received the standard clinical treatment had a mean (sem) lesion size of 3.93 (1.29)% functional renal volume (FRV). The mean lesion size for the 18 kV ramping group was 0.09 (0.01)% FRV, while lesion size for the 24 kV ramping group was 0.51 (0.14)% FRV. The lesion size for both of these groups was significantly smaller than the lesion size in the standard clinical treatment group. The data suggest that initial voltage in a voltage-ramping protocol does not correlate with renal damage. While voltage ramping does reduce injury when compared with SWL with no voltage ramping, starting at low or high voltage produces lesions of the same approximate size. Our findings also suggest that the interval between the initial shocks and the clinical dose of SWs, in our one-step ramping protocol, is important for protecting the kidney against injury.

  19. Durability of truncated dome warnings on existing curb ramps : final report.

    DOT National Transportation Integrated Search

    2004-12-01

    In 2002 the Federal Highway Administration (FHWA) notified the Oregon Department of Transportation (ODOT) that that the state was required to use truncated dome detectable warnings on curb ramps. Products appropriate for use on cured concrete surface...

  20. 40 CFR 1045.505 - How do I test engines using discrete-mode or ramped-modal duty cycles?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 32 2010-07-01 2010-07-01 false How do I test engines using discrete... MARINE ENGINES AND VESSELS Test Procedures § 1045.505 How do I test engines using discrete-mode or ramped... allow you to perform tests with either discrete-mode or ramped-modal sampling. You must use the modal...

  1. A Coupled Model of Langmuir Circulations and Ramp-like Structures in the Upper Ocean Turbulent Boundary Layer

    NASA Astrophysics Data System (ADS)

    Soloviev, A.; Dean, C.; Lukas, R.; Donelan, M. A.; Terray, E. A.

    2016-12-01

    Surface-wave breaking is a powerful mechanism producing significant energy flux to small scale turbulence. Most of the turbulent energy produced by breaking waves dissipates within one significant wave height, while the turbulent diffusion layer extends to approximately ten significant wave heights. Notably, the near-surface shear may practically vanish within the wave-stirred layer due to small-scale turbulent mixing. The surface ocean temperature-salinity structure, circulation, and mass exchanges (including greenhouse gases and pollutants) substantially depend on turbulent mixing and non-local transport in the near-surface layer of the ocean. Spatially coherent organized motions have been recognized as an important part of non-local transport. Langmuir circulation (LC) and ramp-like structures are believed to vertically transfer an appreciable portion of the momentum, heat, gases, pollutants (e.g., oil), and other substances in the upper layer of the ocean. Free surface significantly complicates the analysis of turbulent exchanges at the air-sea interface and the coherent structures are not yet completely understood. In particular, there is growing observational evidence that in the case of developing seas when the wind direction may not coincide with the direction of the energy containing waves, the Langmuir lines are oriented in the wind rather than the wave direction. In addition, the vortex force due to Stokes drift in traditional models is altered in the breaking-wave-stirred layer. Another complication is that the ramp-like structures in the upper ocean turbulent boundary layer have axes perpendicular to the axes of LC. The ramp-like structures are not considered in the traditional model. We have developed a new model, which treats the LC and ramp-like structures in the near-surface layer of the ocean as a coupled system. Using computational fluid dynamics tools (LES), we have been able to reproduce both LC and ramp-like structures coexisting in space

  2. Comparative Molecular Dynamics Simulations of Mitogen-Activated Protein Kinase-Activated Protein Kinase 5

    PubMed Central

    Lindin, Inger; Wuxiuer, Yimingjiang; Ravna, Aina Westrheim; Moens, Ugo; Sylte, Ingebrigt

    2014-01-01

    The mitogen-activated protein kinase-activated protein kinase MK5 is a substrate of the mitogen-activated protein kinases p38, ERK3 and ERK4. Cell culture and animal studies have demonstrated that MK5 is involved in tumour suppression and promotion, embryogenesis, anxiety, cell motility and cell cycle regulation. In the present study, homology models of MK5 were used for molecular dynamics (MD) simulations of: (1) MK5 alone; (2) MK5 in complex with an inhibitor; and (3) MK5 in complex with the interaction partner p38α. The calculations showed that the inhibitor occupied the active site and disrupted the intramolecular network of amino acids. However, intramolecular interactions consistent with an inactive protein kinase fold were not formed. MD with p38α showed that not only the p38 docking region, but also amino acids in the activation segment, αH helix, P-loop, regulatory phosphorylation region and the C-terminal of MK5 may be involved in forming a very stable MK5-p38α complex, and that p38α binding decreases the residual fluctuation of the MK5 model. Electrostatic Potential Surface (EPS) calculations of MK5 and p38α showed that electrostatic interactions are important for recognition and binding. PMID:24651460

  3. Temporary microglia-depletion after cosmic radiation modifies phagocytic activity and prevents cognitive deficits.

    PubMed

    Krukowski, Karen; Feng, Xi; Paladini, Maria Serena; Chou, Austin; Sacramento, Kristen; Grue, Katherine; Riparip, Lara-Kirstie; Jones, Tamako; Campbell-Beachler, Mary; Nelson, Gregory; Rosi, Susanna

    2018-05-18

    Microglia are the main immune component in the brain that can regulate neuronal health and synapse function. Exposure to cosmic radiation can cause long-term cognitive impairments in rodent models thereby presenting potential obstacles for astronauts engaged in deep space travel. The mechanism/s for how cosmic radiation induces cognitive deficits are currently unknown. We find that temporary microglia depletion, one week after cosmic radiation, prevents the development of long-term memory deficits. Gene array profiling reveals that acute microglia depletion alters the late neuroinflammatory response to cosmic radiation. The repopulated microglia present a modified functional phenotype with reduced expression of scavenger receptors, lysosome membrane protein and complement receptor, all shown to be involved in microglia-synapses interaction. The lower phagocytic activity observed in the repopulated microglia is paralleled by improved synaptic protein expression. Our data provide mechanistic evidence for the role of microglia in the development of cognitive deficits after cosmic radiation exposure.

  4. Parametric study of a simultaneous pitch/yaw thrust vectoring single expansion ramp nozzle

    NASA Technical Reports Server (NTRS)

    Schirmer, Alberto W.; Capone, Francis J.

    1989-01-01

    In the course of the last eleven years, the concept of thrust vectoring has emerged as a promising method of enhancing aircraft control capabilities in post-stall flight incursions during combat. In order to study the application of simultaneous pitch and yaw vectoring to single expansion ramp nozzles, a static test was conducted in the NASA-Langley 16 foot transonic tunnel. This investigation was based on internal performance data provided by force, mass flow and internal pressure measurements at nozzle pressure ratios up to 8. The internal performance characteristics of the nozzle were studied for several combinations of six different parameters: yaw vectoring angle, pitch vectoring angle, upper ramp cutout, sidewall hinge location, hinge inclination angle and sidewall containment. Results indicated a 2-to- 3-percent decrease in resultant thrust ratio with vectoring in either pitch or yaw. Losses were mostly associated with the turning of supersonic flow. Resultant thrust ratios were also decreased by sideways expansion of the jet. The effects of cutback corners in the upper ramp and lower flap on performance were small. Maximum resultant yaw vector angles, about half of the flap angle, were achieved for the configuration with the most forward hinge location.

  5. Leaf Treatments with a Protein-Based Resistance Inducer Partially Modify Phyllosphere Microbial Communities of Grapevine

    PubMed Central

    Cappelletti, Martina; Perazzolli, Michele; Antonielli, Livio; Nesler, Andrea; Torboli, Esmeralda; Bianchedi, Pier L.; Pindo, Massimo; Puopolo, Gerardo; Pertot, Ilaria

    2016-01-01

    Protein derivatives and carbohydrates can stimulate plant growth, increase stress tolerance, and activate plant defense mechanisms. However, these molecules can also act as a nutritional substrate for microbial communities living on the plant phyllosphere and possibly affect their biocontrol activity against pathogens. We investigated the mechanisms of action of a protein derivative (nutrient broth, NB) against grapevine downy mildew, specifically focusing on the effects of foliar treatments on plant defense stimulation and on the composition and biocontrol features of the phyllosphere microbial populations. NB reduced downy mildew symptoms and induced the expression of defense-related genes in greenhouse- and in vitro-grown plants, indicating the activation of grapevine resistance mechanisms. Furthermore, NB increased the number of culturable phyllosphere bacteria and altered the composition of bacterial and fungal populations on leaves of greenhouse-grown plants. Although, NB-induced changes on microbial populations were affected by the structure of indigenous communities originally residing on grapevine leaves, degrees of disease reduction and defense gene modulation were consistent among the experiments. Thus, modifications in the structure of phyllosphere populations caused by NB application could partially contribute to downy mildew control by competition for space or other biocontrol strategies. Particularly, changes in the abundance of phyllosphere microorganisms may provide a contribution to resistance induction, partially affecting the hormone-mediated signaling pathways involved. Modifying phyllosphere populations by increasing natural biocontrol agents with the application of selected nutritional factors can open new opportunities in terms of sustainable plant protection strategies. PMID:27486468

  6. Accelerating yield ramp through design and manufacturing collaboration

    NASA Astrophysics Data System (ADS)

    Sarma, Robin C.; Dai, Huixiong; Smayling, Michael C.; Duane, Michael P.

    2004-12-01

    Ramping an integrated circuit from first silicon bring-up to production yield levels is a challenge for all semiconductor products on the path to profitable market entry. Two approaches to accelerating yield ramp are presented. The first is the use of laser mask writers for fast throughput, high yield, and cost effective pattern transfer. The second is the use of electrical test to find a defect and identify the physical region to probe in failure analysis that is most likely to uncover the root cause. This provides feedback to the design team on modifications to make to the design to avoid the yield issue in a future tape-out revision. Additionally, the process parameter responsible for the root cause of the defect is forward annotated through the design, mask and wafer coordinate systems so it can be monitored in-line on subsequent lots of the manufacturing run. This results in an improved recipe for the manufacturing equipment to potentially prevent the recurrence of the defect and raise yield levels on the following material. The test diagnostics approach is enabled by the seamless traceability of a feature across the design, photomask and wafer, made possible by a common data model for design, mask pattern generation and wafer fabrication.

  7. 40 CFR 1039.505 - How do I test engines using steady-state duty cycles, including ramped-modal testing?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...-state duty cycles, including ramped-modal testing? 1039.505 Section 1039.505 Protection of Environment... duty cycles, including ramped-modal testing? This section describes how to test engines under steady-state conditions. In some cases, we allow you to choose the appropriate steady-state duty cycle for an...

  8. AMP-activated Protein Kinase Mediates Apoptosis in Response to Bioenergetic Stress through Activation of the Pro-apoptotic Bcl-2 Homology Domain-3-only Protein BMF*

    PubMed Central

    Kilbride, Seán M.; Farrelly, Angela M.; Bonner, Caroline; Ward, Manus W.; Nyhan, Kristine C.; Concannon, Caoimhín G.; Wollheim, Claes B.; Byrne, Maria M.; Prehn, Jochen H. M.

    2010-01-01

    Heterozygous loss-of-function mutations in the hepatocyte nuclear factor 1A (HNF1A) gene result in the pathogenesis of maturity-onset diabetes-of-the-young type 3, (HNF1A-MODY). This disorder is characterized by a primary defect in metabolism-secretion coupling and decreased beta cell mass, attributed to excessive beta cell apoptosis. Here, we investigated the link between energy stress and apoptosis activation following HNF1A inactivation. This study employed single cell fluorescent microscopy, flow cytometry, gene expression analysis, and gene silencing to study the effects of overexpression of dominant-negative (DN)-HNF1A expression on cellular bioenergetics and apoptosis in INS-1 cells. Induction of DN-HNF1A expression led to reduced ATP levels and diminished the bioenergetic response to glucose. This was coupled with activation of the bioenergetic stress sensor AMP-activated protein kinase (AMPK), which preceded the onset of apoptosis. Pharmacological activation of AMPK using aminoimidazole carboxamide ribonucleotide (AICAR) was sufficient to induce apoptosis in naive cells. Conversely, inhibition of AMPK with compound C or AMPKα gene silencing protected against DN-HNF1A-induced apoptosis. Interestingly, AMPK mediated the induction of the pro-apoptotic Bcl-2 homology domain-3-only protein Bmf (Bcl-2-modifying factor). Bmf expression was also elevated in islets of DN-HNF1A transgenic mice. Furthermore, knockdown of Bmf expression in INS-1 cells using siRNA was sufficient to protect against DN-HNF1A-induced apoptosis. Our study suggests that overexpression of DN-HNF1A induces bioenergetic stress and activation of AMPK. This in turn mediates the transcriptional activation of the pro-apoptotic Bcl-2-homology protein BMF, coupling prolonged energy stress to apoptosis activation. PMID:20841353

  9. View of Facility No. S359 (Seaplane Ramp 3), with Koolau ...

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

    View of Facility No. S359 (Seaplane Ramp 3), with Koolau Mountain Range in background - U.S. Naval Base, Pearl Harbor, Seaplane Runways-1933 Type, South shore of Ford Island, near Lexington Boulevard, Pearl City, Honolulu County, HI

  10. RAMP TO DOCK ON RIVERBANK SOUTH OF THE RAILROAD BRIDGE, ...

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

    RAMP TO DOCK ON RIVERBANK SOUTH OF THE RAILROAD BRIDGE, LOOKING SOUTH. PA-1-48 AND PA-1-49 CAN BE PAIRED TO FORM A PANORAMA SHOWING THE RELATIONSHIP BETWEEN THE RIVERBANK AND THE MEADOW. - John Bartram House & Garden, 54th Street & Lindbergh Boulevard, Philadelphia, Philadelphia County, PA

  11. TRACC_PB SOSS Integrated Traffic Simulation for CLT Ramp Operation

    NASA Technical Reports Server (NTRS)

    Okuniek, Nikolai; Zhu, Zhifan

    2017-01-01

    This presentation provides the current task under the NASA-DLR research collaboration for airport surface. It presents the effort done to adapt TRACC and SOSS software components to simulate airport (CLT) ramp area traffic management using TRACC's conflict free taxi trajectory optimization and SOSS's fast time simulation platform.

  12. Evaluation of the quality of care of a multi-disciplinary Risk Factor Assessment and Management Programme for Hypertension (RAMP-HT).

    PubMed

    Yu, Esther Yee Tak; Wan, Eric Yuk Fai; Chan, Karina Hiu Yen; Wong, Carlos King Ho; Kwok, Ruby Lai Ping; Fong, Daniel Yee Tak; Lam, Cindy Lo Kuen

    2015-06-19

    There is some evidence to support a risk-stratified, multi-disciplinary approach to manage patients with hypertension in primary care. The aim of this study is to evaluate the quality of care (QOC) of a multi-disciplinary Risk Assessment and Management Programme for Hypertension (RAMP-HT) for hypertensive patients in busy government-funded primary care clinics in Hong Kong. The objectives are to develop an evidence-based, structured and comprehensive evaluation framework on quality of care, to enhance the QOC of the RAMP-HT through an audit spiral of two evaluation cycles and to determine the effectiveness of the programme in reducing cardiovascular disease (CVD) risk. A longitudinal study is conducted using the Action Learning and Audit Spiral methodologies to measure whether pre-set target standards of care intended by the RAMP-HT are achieved. A structured evaluation framework on the quality of structure, process and outcomes of care has been developed based on the programme objectives and literature review in collaboration with the programme workgroup and health service providers. Each participating clinic is invited to complete a structure of care evaluation questionnaire in each evaluation cycle. The data of all patients who have enrolled into the RAMP-HT in the pre-defined evaluation periods are used for the evaluation of the process and outcomes of care in each evaluation cycle. For evaluation of the effectiveness of RAMP-HT, the primary outcomes including blood pressure (both systolic and diastolic), low-density lipoprotein cholesterol and estimated 10-year CVD risk of RAMP-HT participants are compared to those of hypertensive patients in usual care without RAMP-HT. The QOC and effectiveness of the RAMP-HT in improving clinical and patient-reported outcomes for patients with hypertension in normal primary care will be determined. Possible areas for quality enhancement and standards of good practice will be established to inform service planning and policy

  13. Identification of O-linked β-d-N-acetylglucosamine-Modified Proteins from Arabidopsis

    PubMed Central

    Xu, Shou-Ling; Chalkley, Robert J.; Wang, Zhi-Yong; Burlingame, Alma L.

    2013-01-01

    The posttranslational modification of proteins with O-linked β-d-N-acetylglucosamine (O-GlcNAc) on serine and threonine residues occurs in all animals and plants. This modification is dynamic and ubiquitous, and regulates many cellular processes, including transcription, signaling and cytokinesis and is associated with several diseases. Cycling of O-GlcNAc is tightly regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Plants have two OGTs, SPINDLY (SPY) and SECRET AGENT (SEC); disruption of both causes embryo lethality. Despite O-GlcNAc modification of proteins being discovered more than 20-years ago, identification and mapping of protein GlcNAcylation is still a challenging task. Here we describe the use of lectin affinity chromatography combined with electron transfer dissociation mass spectrometry to enrich and to detect O-GlcNAc modified peptides from Arabidopsis. PMID:22576084

  14. A trans-membrane segment inside the ribosome exit tunnel triggers RAMP4 recruitment to the Sec61p translocase

    PubMed Central

    2009-01-01

    Membrane protein integration occurs predominantly at the endoplasmic reticulum and is mediated by the translocon, which is formed by the Sec61p complex. The translocon binds to the ribosome at the polypeptide exit site such that integration occurs in a cotranslational manner. Ribosomal protein Rpl17 is positioned such that it contacts both the ribosome exit tunnel and the surface of the ribosome near the exit site, where it is intimately associated with the translocon. The presence of a trans-membrane (TM) segment inside the ribosomal exit tunnel leads to the recruitment of RAMP4 to the translocon at a site adjacent to Rpl17. This suggests a signaling function for Rpl17 such that it can recognize a TM segment inside the ribosome and triggers rearrangements of the translocon, priming it for subsequent TM segment integration. PMID:19468070

  15. Comparison of Macintosh and Airtraq™ laryngoscopes in obese patients placed in the ramped position.

    PubMed

    Ranieri, D; Filho, S M; Batista, S; do Nascimento, P

    2012-09-01

    This study compared intubation conditions produced by the Macintosh and Airtraq™ laryngoscopes when used in obese patients in the ramped position. One hundred and thirty-two patients having bariatric surgery were placed in the ramped position and randomly assigned to have their tracheas intubated using either the Macintosh (n=64) or an Airtraq (n=68) laryngoscope. Mean (SD) intubation times were 37 (23) s and 14 (3) s for Macintosh and Airtraq, respectively (p<0.0001). Compared with the Macintosh laryngoscope, the Airtraq laryngoscope provided an improved vocal cord view as assessed by the Cormack and Lehane score (number of patients with Cormack-Lehane scores of 1/2/3/4/37/20/4/3 for the Macintosh, and 65/3/0/0 for the Airtraq laryngoscopes, p<0.0001). One patient in the Macintosh group had a failed intubation and intubation was achieved with the Airtraq. For obese patients in ramped position, Airtraq affords faster tracheal intubation than the Macintosh laryngoscope. Anaesthesia © 2012 The Association of Anaesthetists of Great Britain and Ireland.

  16. Pokemon siRNA Delivery Mediated by RGD-Modified HBV Core Protein Suppressed the Growth of Hepatocellular Carcinoma.

    PubMed

    Kong, Jing; Liu, Xiaoping; Jia, Jianbo; Wu, Jinsheng; Wu, Ning; Chen, Jun; Fang, Fang

    2015-10-01

    Hepatocellular carcinoma (HCC) is a deadly human malignant tumor that is among the most common cancers in the world, especially in Asia. Hepatitis B virus (HBV) infection has been well established as a high risk factor for hepatic malignance. Studies have shown that Pokemon is a master oncogene for HCC growth, suggesting it as an ideal therapeutic target. However, efficient delivery system is still lacking for Pokemon targeting treatment. In this study, we used core proteins of HBV, which is modified with RGD peptides, to construct a biomimetic vector for the delivery of Pokemon siRNAs (namely, RGD-HBc-Pokemon siRNA). Quantitative PCR and Western blot assays revealed that RGD-HBc-Pokemon siRNA possessed the highest efficiency of Pokemon suppression in HCC cells. In vitro experiments further indicated that RGD-HBc-Pokemon-siRNA exerted a higher tumor suppressor activity on HCC cell lines, evidenced by reduced proliferation and attenuated invasiveness, than Pokemon-siRNA or RGD-HBc alone. Finally, animal studies demonstrated that RGD-HBc-Pokemon siRNA suppressed the growth of HCC xenografts in mice by a greater extent than Pokemon-siRNA or RGD-HBc alone. Based on the above results, Pokemon siRNA delivery mediated by RGD-modified HBV core protein was shown to be an effective strategy of HCC gene therapy.

  17. Service building no. 620. Details of ramps in south end ...

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

    Service building no. 620. Details of ramps in south end of service building (Dry Dock Associates, November 7, 1941). In files of Cushman & Wakefiled, building no. 501, Philadelphia Naval Business Center. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Service Building, Dry Docks No. 4 & 5, League Island, Philadelphia, Philadelphia County, PA

  18. 7 CFR 1944.684 - Extending grant agreement and modifying the statement of activities.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 13 2010-01-01 2009-01-01 true Extending grant agreement and modifying the statement... Preservation Grants § 1944.684 Extending grant agreement and modifying the statement of activities. (a) All requests extending the original grant agreement or modifying the HPG program's statement of activities must...

  19. 7 CFR 1944.684 - Extending grant agreement and modifying the statement of activities.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 13 2013-01-01 2013-01-01 false Extending grant agreement and modifying the statement... Preservation Grants § 1944.684 Extending grant agreement and modifying the statement of activities. (a) All requests extending the original grant agreement or modifying the HPG program's statement of activities must...

  20. 7 CFR 1944.684 - Extending grant agreement and modifying the statement of activities.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 13 2014-01-01 2013-01-01 true Extending grant agreement and modifying the statement... Preservation Grants § 1944.684 Extending grant agreement and modifying the statement of activities. (a) All requests extending the original grant agreement or modifying the HPG program's statement of activities must...

  1. Screening for Glycosylphosphatidylinositol-Modified Cell Wall Proteins in Pichia pastoris and Their Recombinant Expression on the Cell Surface

    PubMed Central

    Zhang, Li; Liang, Shuli; Zhou, Xinying; Jin, Zi; Jiang, Fengchun; Han, Shuangyan; Zheng, Suiping

    2013-01-01

    Glycosylphosphatidylinositol (GPI)-anchored glycoproteins have various intrinsic functions in yeasts and different uses in vitro. In the present study, the genome of Pichia pastoris GS115 was screened for potential GPI-modified cell wall proteins. Fifty putative GPI-anchored proteins were selected on the basis of (i) the presence of a C-terminal GPI attachment signal sequence, (ii) the presence of an N-terminal signal sequence for secretion, and (iii) the absence of transmembrane domains in mature protein. The predicted GPI-anchored proteins were fused to an alpha-factor secretion signal as a substitute for their own N-terminal signal peptides and tagged with the chimeric reporters FLAG tag and mature Candida antarctica lipase B (CALB). The expression of fusion proteins on the cell surface of P. pastoris GS115 was determined by whole-cell flow cytometry and immunoblotting analysis of the cell wall extracts obtained by β-1,3-glucanase digestion. CALB displayed on the cell surface of P. pastoris GS115 with the predicted GPI-anchored proteins was examined on the basis of potential hydrolysis of p-nitrophenyl butyrate. Finally, 13 proteins were confirmed to be GPI-modified cell wall proteins in P. pastoris GS115, which can be used to display heterologous proteins on the yeast cell surface. PMID:23835174

  2. STEREO Observations of Waves in the Ramp Regions of Interplanetary Shocks

    NASA Astrophysics Data System (ADS)

    Cohen, Z.; Breneman, A. W.; Cattell, C. A.; Davis, L.; Grul, P.; Kersten, K.; Wilson, L. B., III

    2017-12-01

    Determining the role of plasma waves in providing energy dissipation at shock waves is of long-standing interest. Interplanetary (IP) shocks serve as a large database of low Mach number shocks. We examine electric field waveforms captured by the Time Domain Sampler (TDS) on the STEREO spacecraft during the ramps of IP shocks, with emphasis on captures lasting 2.1 seconds. Previous work has used captures of shorter duration (66 and 131 ms on STEREO, and 17 ms on WIND), which allowed for observation of waves with maximum (minimum) frequencies of 125 kHz (15 Hz), 62.5 kHz (8 Hz), and 60 kHz (59 Hz), respectively. The maximum frequencies are comparable to 2-8 times the plasma frequency in the solar wind, enabling observation of Langmuir waves, ion acoustic, and some whistler-mode waves. The 2 second captures resolve lower frequencies ( few Hz), which allows us to analyze packet structure of the whistler-mode waves and some ion acoustic waves. The longer capture time also improves the resolvability of simultaneous wave modes and of waves with frequencies on the order of 10s of Hz. Langmuir waves, however, cannot be identified at this sampling rate, since the plasma frequency is usually higher than 3.9 kHz. IP shocks are identified from multiple databases (Helsinki heliospheric shock database at http://ipshocks.fi, and the STEREO level 3 shock database at ftp://stereoftp.nascom.nasa.gov/pub/ins_data/impact/level3/). Our analysis focuses on TDS captures in shock ramp regions, with ramp durations determined from magnetic field data taken at 8 Hz. Software is used to identify multiple wave modes in any given capture and classify waves as Langmuir, ion acoustic, whistler, lower hybrid, electron cyclotron drift instability, or electrostatic solitary waves. Relevant frequencies are determined from density and magnetic field data collected in situ. Preliminary results suggest that large amplitude (≥ 5 mV/m) ion acoustic waves are most prevalent in the ramp, in agreement with

  3. Complement activation promotes muscle inflammation during modified muscle use

    NASA Technical Reports Server (NTRS)

    Frenette, J.; Cai, B.; Tidball, J. G.

    2000-01-01

    Modified muscle use can result in muscle inflammation that is triggered by unidentified events. In the present investigation, we tested whether the activation of the complement system is a component of muscle inflammation that results from changes in muscle loading. Modified rat hindlimb muscle loading was achieved by removing weight-bearing from the hindlimbs for 10 days followed by reloading through normal ambulation. Experimental animals were injected with the recombinant, soluble complement receptor sCR1 to inhibit complement activation. Assays for complement C4 or factor B in sera showed that sCR1 produced large reductions in the capacity for activation of the complement system through both the classical and alternative pathways. Analysis of complement C4 concentration in serum in untreated animals showed that the classical pathway was activated during the first 2 hours of reloading. Analysis of factor B concentration in untreated animals showed activation of the alternative pathway at 6 hours of reloading. Administration of sCR1 significantly attenuated the invasion of neutrophils (-49%) and ED1(+) macrophages (-52%) that occurred in nontreated animals after 6 hours of reloading. The presence of sCR1 also reduced significantly the degree of edema by 22% as compared to untreated animals. Together, these data show that increased muscle loading activated the complement system which then briefly contributes to the early recruitment of inflammatory cells during modified muscle loading.

  4. Design of a Sample Recovery Assembly for Magnetic Ramp-Wave Loading

    NASA Astrophysics Data System (ADS)

    Chantrenne, S.; Wise, J. L.; Asay, J. R.; Kipp, M. E.; Hall, C. A.

    2009-06-01

    Characterization of material behavior under dynamic loading requires studies at strain rates ranging from quasi-static to the limiting values of shock compression. For completeness, these studies involve complementary time-resolved data, which define the mechanical constitutive properties, and microstructural data, which reveal physical mechanisms underlying the observed mechanical response. Well-preserved specimens must be recovered for microstructural investigations. Magnetically generated ramp waves produce strain rates lower than those associated with shock waves, but recovery methods have been lacking for this type of loading. We adapted existing shock recovery techniques for application to magnetic ramp loading using 2-D and 3-D ALEGRA MHD code calculations to optimize the recovery design for mitigation of undesired late-time processing of the sample due to edge effects and secondary stress waves. To assess the validity of our simulations, measurements of sample deformation were compared to wavecode predictions.

  5. Experimental investigation of a 0.15 scale model of a conformal variable-ramp inlet for the F-16 airplane

    NASA Technical Reports Server (NTRS)

    Hawkins, J. E.

    1980-01-01

    A 0.15 scale model of a proposed conformal variable-ramp inlet for the Multirole Fighter was tested from Mach 0.8 to 2.2 at a wide range of angles of attack and sideslip. Inlet ramp angle was varied to optimize ramp angle as a function of engine airflow, Mach number, angle of attack, and angle of sideslip. Several inlet configuration options were investigated to study their effects on inlet operation and to establish the final flight configuration. These variations were cowl sidewall cutback, cowl lip bluntness, boundary layer bleed, and first-ramp leading edge shape. Diagnostic and engine face instrumentation were used to evaluate inlet operation at various inlet stations and at the inlet/engine interface. Pressure recovery and stability of the inlet were satisfactory for the proposed application. On the basis of an engine stability audit of the worst-case instantaneous distortion patterns, no inlet/engine compatibility problems are expected for normal operations.

  6. Power reserve following ramp-incremental cycling to exhaustion: implications for muscle fatigue and function.

    PubMed

    Hodgson, Michael D; Keir, Daniel A; Copithorne, David B; Rice, Charles L; Kowalchuk, John M

    2018-04-26

    In ramp-incremental cycling exercise, some individuals are capable of producing power output (PO) in excess of that produced at their limit of tolerance (LoT) while others cannot. This study sought to describe the: 1) prevalence of a "power reserve" within a group of young men (n=21; mean {plus minus} SD: age 25{plus minus}4 years; V̇O 2max 45{plus minus}8 ml•kg -1 •min -1 ); and 2) muscle fatigue characteristics of those with and without a power reserve. Power reserve was determined as the difference between peak PO achieved during a ramp-incremental test to exhaustion and maximal, single-leg isokinetic dynamometer power. Pre- versus post-exercise changes in voluntary and electrically-stimulated single-leg muscle force production measures (maximal voluntary contraction, voluntary activation, maximal isotonic velocity and isokinetic power; 1-, 10-, 50-Hz torque and 10/50-Hz ratio), V̇O 2max and constant-PO cycling time-to-exhaustion also were assessed. A dichotomy in power reserve was prevalent within the sample resulting in two groups: 1) "No Reserve" (NRES: <5% reserve; n=10) and 2) "Reserve" (RES: >15% reserve; n=11). At the LoT, all participants had achieved V̇O 2max . Muscle fatigue was evident in both groups, although the NRES group had greater reductions (p<0.05) in 10-Hz peak torque (PT), 10/50 Hz ratio, and maximal velocity. Time-to-exhaustion during the constant-PO test was 22{plus minus}16% greater (p<0.05) in RES (116{plus minus}19 s; PO = 317{plus minus}52 W) than in NRES (90{plus minus}23 s; PO = 337{plus minus}71 W), despite similar ramp-incremental exercise durations and V̇O 2max between groups. The differences in muscle fatigue and function between groups suggest that the mechanisms contributing to the LoT are not uniform.

  7. Controls on facies and sequence stratigraphy of an upper Miocene carbonate ramp and platform, Melilla basin, NE Morocco

    USGS Publications Warehouse

    Cunningham, K.J.; Collins, Luke S.

    2002-01-01

    Upwelling of cool seawater, paleoceanographic circulation, paleoclimate, local tectonics and relative sea-level change controlled the lithofacies and sequence stratigraphy of a carbonate ramp and overlying platform that are part of a temporally well constrained carbonate complex in the Melilla basin, northeastern Morocco. At Melilla, from oldest to youngest, a third-order depositional sequence within the carbonate complex contains (1) a retrogradational, transgressive, warm temperate-type rhodalgal ramp; (2) an early highstand, progradational, bioclastic platform composed mainly of a temperate-type, bivalve-rich molechfor facies; and (3) late highstand, progradational to downstepping, subtropical/tropical-type chlorozoan fringing Porites reefs. The change from rhodalgal ramp to molechfor platform occurred at 7.0??0.14 Ma near the Tortonian/Messinian boundary. During a late stage in the development of the bioclastic platform a transition from temperate-type molechfor facies to subtropical/tropical-type chlorozoan facies occurred and is bracketed by chron 3An.2n (??? 6.3-6.6 Ma). Comparison to a well-dated carbonate complex in southeastern Spain at Cabo de Gata suggests that upwelling of cool seawater influenced production of temperate-type limestone within the ramp and platform at Melilla during postulated late Tortonian-early Messinian subtropical/tropical paleoclimatic conditions in the western Paleo-Mediterranean region. The upwelling of cool seawater across the bioclastic platform at Melilla could be related to the beginning of 'siphoning' of deep, cold Atlantic waters into the Paleo-Mediterranean Sea at 7.17 Ma. The facies change within the bioclastic platform from molechfor to chlorozoan facies may be coincident with a reduction of the siphoning of Atlantic waters and the end of upwelling at Melilla during chron 3An.2n. The ramp contains one retrogradational parasequence and the bioclastic platform three progradational parasequences. Minor erosional surfaces

  8. Mixed Linear/Square-Root Encoded Single Slope Ramp Provides a Fast, Low Noise Analog to Digital Converter with Very High Linearity for Focal Plane Arrays

    NASA Technical Reports Server (NTRS)

    Wrigley, Christopher James (Inventor); Hancock, Bruce R. (Inventor); Cunningham, Thomas J. (Inventor); Newton, Kenneth W. (Inventor)

    2014-01-01

    An analog-to-digital converter (ADC) converts pixel voltages from a CMOS image into a digital output. A voltage ramp generator generates a voltage ramp that has a linear first portion and a non-linear second portion. A digital output generator generates a digital output based on the voltage ramp, the pixel voltages, and comparator output from an array of comparators that compare the voltage ramp to the pixel voltages. A return lookup table linearizes the digital output values.

  9. Stability of hemostatic proteins in canine fresh-frozen plasma thawed with a modified commercial microwave warmer or warm water bath.

    PubMed

    Pashmakova, Medora B; Barr, James W; Bishop, Micah A

    2015-05-01

    To compare stability of hemostatic proteins in canine fresh-frozen plasma (FFP) thawed with a modified commercial microwave warmer (MCM) or warm water bath (37°C; WWB) or at room temperature (22°C). Fresh-frozen plasma obtained from 8 canine donors of a commercial blood bank. A commercial microwave warmer was modified with a thermocouple to measure surface temperature of bags containing plasma. The MCM and a WWB were each used to concurrently thaw a 60-mL bag of plasma obtained from the same donor. Two 3-mL control aliquots of FFP from each donor were thawed to room temperature without use of a heating device. Concentrations of hemostatic proteins, albumin, and D-dimers; prothrombin time (PT); and activated partial thromboplastin time (aPTT) were determined for all samples. Significant decreases in concentrations of factors II, IX, X, XI, fibrinogen, von Willebrand factor, antithrombin, protein C, and albumin and significant increases in PT and aPTT were detected for plasma thawed with the MCM, compared with results for samples thawed with the WWB. Concentrations of factors VII, VIII, and XII were not significantly different between plasma thawed with the MCM and WWB. Concentrations of D-dimers were above the reference range for all thawed samples regardless of thawing method. No significant differences in factor concentrations were detected between control and WWB-thawed samples. Significant differences in hemostatic protein concentrations and coagulation times were detected for plasma thawed with an MCM but not between control and WWB-thawed samples. Clinical importance of these changes should be investigated.

  10. Turbulent boundary layer separation over a rearward facing ramp and its control through mechanical excitation

    NASA Technical Reports Server (NTRS)

    Mckinzie, Daniel J., Jr.

    1991-01-01

    A vane oscillating about a fixed point at the inlet to a two-dimensional 20 degree rearward facing ramp has proven effective in delaying the separation of a turbulent boundary layer. Measurements of the ramp surface static pressure coefficient obtained under the condition of vane oscillation and constant inlet velocity revealed that two different effects occurred with surface distance along the ramp. In the vicinity of the oscillating vane, the pressure coefficients varied as a negative function of the vane's trailing edge rms velocity; the independent variable on which the rms velocity depends are the vane's oscillation frequency and its displacement amplitude. From a point downstream of the vane to the exit of the ramp; however, the pressure coefficient varied as a more complex function of the two independent variables. That is, it was found to vary as a function of the vane's oscillation frequency throughout the entire range of frequencies covered during the test, but over only a limited range of the trailing edge displacement amplitudes covered. More specifically, the value of the pressure coefficient was independent of increases in the vane's displacement amplitude above approximately 35 inner wall units of the boundary layer. Below this specific amplitude it varied as a function of the vane's trailing edge rms velocity. This height is close to the upper limit of the buffer layer. A parametric study was made to determine the variation of the maximum static pressure recovery as a function of the vane's oscillation frequency, for several ramp inlet velocities and a constant displacement amplitude of the vane's trailing edge. The results indicate that the phenomenon producing the optimum delay of separation may be Strouhal number dependent. Corona anemometer measurements obtained in the inner wall regions of the boundary layer for the excited case reveal a large range of unsteadiness in the local velocities. These measurements imply the existence of inflections

  11. Deformation of the Pacific Plate above the Alpine fault ramp and its relationship to expulsion of metamorphic fluids: An array of backshears

    NASA Astrophysics Data System (ADS)

    Wightman, Ruth H.; Little, Timothy A.

    A ˜2 km-wide array of near-vertical backshears in the central Southern Alps, New Zealand, is interpreted to have slipped in an escalator-like way to up-ramp the Pacific Plate onto the Alpine Fault ramp, and to play an important role in channelling metamorphic fluids upward through this active orogen. The oblique-slip backshears formed in the lower crust, are evenly spaced (˜30 cm), and have an average offset of 14 cm that is brittle to ductile and extend over 500 m in vertical length. Cumulative vertical displacements suggest that the causative ramp-step in the Alpine Fault at depth had an angle of 22±8°. Microscale shearing between the backshears probably accomplished additional crustal tilting to ˜45°. We infer this shearing was focused above the basal ramp-step, was transient, and aseismic. Focal mechanisms of earthquakes in the Southern Alps suggest that similar backshearing may be accumulating at depth today, where it is linked to seismic-slip on upper crustal faults. Fluid was integral to the formation and accumulation of shear along the backshears. Near-lithostatic fluid pressures triggered deep, brittle shear failure (>20 km). The steep, dilative backshears allowed these fluids to escape upwards through low permeability (1 × 10-18m2) schist. Fluid expulsion may thus have accomplished a devolatilisation and rheological strengthening along the Alpine mylonite source region at depth, while also causing a hydrolytic weakening of the fluid-invaded rocks (especially quartz veins) in the Pacific Plate. These coupled strength changes may have enhanced the local partitioning of deformation onto steep planes in the Alpine Fault hangingwall.

  12. Power ramp rate capabilities of a 5 kW proton exchange membrane fuel cell system with discrete ejector control

    NASA Astrophysics Data System (ADS)

    Nikiforow, K.; Pennanen, J.; Ihonen, J.; Uski, S.; Koski, P.

    2018-03-01

    The power ramp rate capabilities of a 5 kW proton exchange membrane fuel cell (PEMFC) system are studied theoretically and experimentally for grid support service applications. The fuel supply is implemented with a fixed-geometry ejector and a discrete control solution without any anode-side pressure fluctuation suppression methods. We show that the stack power can be ramped up from 2.0 kW to 4.0 kW with adequate fuel supply and low anode pressure fluctuations within only 0.1 s. The air supply is implemented with a centrifugal blower. Air supply ramp rates are studied with a power increase executed within 1 and 0.2 s after the request, the time dictated by grid support service requirements in Finland and the UK. We show that a power ramp-up from 2.0 kW to 3.7 kW is achieved within 1 s with an initial air stoichiometry of 2.5 and within 0.2 s with an initial air stoichiometry of 7.0. We also show that the timing of the power ramp-up affects the achieved ancillary power capacity. This work demonstrates that hydrogen fueled and ejector-based PEMFC systems can provide a significant amount of power in less than 1 s and provide valuable ancillary power capacity for grid support services.

  13. Experiencing production ramp-up education for engineers

    NASA Astrophysics Data System (ADS)

    Bassetto, S.; Fiegenwald, V.; Cholez, C.; Mangione, F.

    2011-08-01

    This paper presents a game of industrialisation, based on a paper airplane, that mimics real world production ramp-up and blends classical engineering courses together. It is based on a low cost product so that it can be mass produced. The game targets graduate students and practitioners in engineering fields. For students, it offers an experiment in which methods learned in separate courses can be applied. For practitioners, it affords an opportunity to engage in reflexive practices related to industrialisation. Both students and practitioners are able to experience integrated management, required by industrialisation, in a controlled environment: the laboratory.

  14. Characterization of nano-clay reinforced phytagel-modified soy protein concentrate resin.

    PubMed

    Huang, Xiaosong; Netravali, Anil N

    2006-10-01

    Phytagel and nano-clay particles were used to improve the mechanical and thermal properties and moisture resistance of soy protein concentrate (SPC) resin successfully. SPC and Phytagel were mixed together to form a cross-linked structure. The Phytagel-modified SPC resin (PH-SPC) showed improved tensile strength, modulus, moisture resistance, and thermal stability as compared to the unmodified SPC resin. The incorporation of 40% Phytagel and 20% glycerol led to an overall 340% increase in the tensile strength (over 50 MPa) and approximately 360% increase in the Young's modulus (over 710 MPa) of the SPC resin. Nano-clay was uniformly dispersed into PH-SPC resin to further improve the properties. The PH-SPC (40% Phytagel) resin modified with 7% clay nanoparticles (CPH-SPC) had a modulus of 2.1 GPa and a strength of 72.5 MPa. The dynamic mechanical properties such as storage modulus together with the glass transition temperature of the modified resins were also increased by the addition of clay nanoparticles. The moisture resistance of the CPH-SPC resin was higher as compared to both SPC and PH-SPC resins. The thermal stability of the CPH-SPC resin was seen to be higher as compared to the unmodified SPC.

  15. Exploration of the SHRP2 naturalistic driving study data to identify factors related to the selection of freeway ramp design speed.

    DOT National Transportation Integrated Search

    2017-03-01

    This research explored the second Strategic Highway Research Program (SHRP2) Naturalistic Driving Study (NDS) database for the potential to identify freeway entrance and exit ramps and teen drivers behavior while traveling those ramps. This is in ...

  16. Carbohydrate-protein interactions investigated on plastic chips statically coated with hydrophobically modified hydroxyethylcellulose.

    PubMed

    Dang, Fuquan; Maeda, Eiki; Osafune, Tomo; Nakajima, Kazuki; Kakehi, Kazuaki; Ishikawa, Mitsuru; Baba, Yoshinobu

    2009-12-15

    We developed a novel method for rapid screening of carbohydrate-protein interactions using poly(methyl methacrylate) (PMMA) channels statically coated with hydrophobically modified hydroxyethylcellulose (HM-HEC). We found that a self-assembled monolayer (SAM) of HM-HEC on a PMMA surface intact by water allows rapid and reproducible separations of glycan samples using a 20 mM phosphate without HM-HEC. The underlying mechanism for dynamic and static coatings on the PMMA surface is discussed. Simultaneous analysis of the molecular interaction between a complex mixture of carbohydrates from alpha1-acid glycoprotein and proteins has been successfully achieved in PMMA channels statically coated with a SAM of HM-HEC.

  17. Coastal eolian sand-ramp development related to paleo-sea-level changes during the Latest Pleistocene and Holocene (21–0 ka) in San Miguel Island, California, U.S.A.

    USGS Publications Warehouse

    Peterson, Curt D.; Erlandson, Jon M.; Stock, Errol; Hostetler, Steven W.; Price, David M.

    2017-01-01

    Coastal eolian sand ramps (5–130 m elevation) on the northern slope (windward) side of the small San Miguel Island (13 km in W-E length) range in age from late Pleistocene to modern time, though a major hiatus in sand-ramp growth occurred during the early Holocene marine transgression (16–9 ka). The Holocene sand ramps (1–5 m measured thicknesses) currently lack large dune forms, thereby representing deflated erosional remnants, locally covering thicker late Pleistocene sand-ramp deposits. The ramp sand was initially supplied from the adjacent island-shelf platform, extending about 20 km north of the present coastline. The sand-ramp deposits and interbedded loess soils were 14C dated using 112 samples from 32 archaeological sites and other geologic sections. Latest Pleistocene sand ramps (66–18 ka) were derived from across-shelf eolian sand transport during marine low stands. Shoreward wave transport supplied remobilized late Pleistocene sand from the inner shelf to Holocene beaches, where dominant NW winds supplied sand to the sand ramps. The onset dates of the sand-ramp deposition in San Miguel are 7.2 ± 1.5 ka (sample n = 14). The internal strata dates in the vertically accreting sand ramps are 3.4 ± 1.7 ka (n = 34). The sand ramps in San Miguel show wide-scale termination of sand supply in the latest Holocene time. The sand-ramp top dates or burial dates are 1.7 ± 0.9 ka (n = 28). The latest Holocene sand ramps are truncated along most of the island's northern coastline, indicating recent losses of nearshore sand reserves to onshore, alongshore, and, possibly, offshore sand sinks. The truncated sand ramps in San Miguel Island and in other sand-depleted marine coastlines provide warnings about future beach erosion and/or shoreline retreat from accelerated sea-level rise accompanying predicted global warming.

  18. Response of humpback whales (Megaptera novaeangliae) to ramp-up of a small experimental air gun array.

    PubMed

    Dunlop, Rebecca A; Noad, Michael J; McCauley, Robert D; Kniest, Eric; Slade, Robert; Paton, David; Cato, Douglas H

    2016-02-15

    'Ramp-up', or 'soft start', is a mitigation measure used in seismic surveys and involves increasing the radiated sound level over 20-40 min. This study compared the behavioural response in migrating humpback whales to the first stages of ramp-up with the response to a 'constant' source, 'controls' (in which the array was towed but not operated) with groups in the absence of the source vessel used as the 'baseline'. Although the behavioural response, in most groups, resulted in an increase in distance from the source (potential avoidance), there was no evidence that either 'ramp-up' or the constant source at a higher level was superior for triggering whales to move away from the source vessel. 'Control' groups also responded suggesting the presence of the source vessel had some effect. However, the majority of groups appeared to avoid the source vessel at distances greater than the radius of most mitigation zones. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Modifying a standard method allows simultaneous extraction of RNA and protein, enabling detection of enzymes in the rat retina with low expressions and protein levels.

    PubMed

    Agardh, Elisabet; Gustavsson, Carin; Hagert, Per; Nilsson, Marie; Agardh, Carl-David

    2006-02-01

    The aim of the study was to evaluate messenger RNA and protein expression in limited amounts of tissue with low protein content. The Chomczynski method was used for simultaneous extraction of RNA, and protein was modified in the protein isolation step. Template mass and cycling time for the complementary DNA synthesis step of real-time reverse transcription-polymerase chain reaction (RT-PCR) for analysis of catalase, copper/zinc superoxide dismutase, manganese superoxide dismutase, the catalytic subunit of glutamylcysteine ligase, glutathione peroxidase 1, and the endogenous control cyclophilin B (CypB) were optimized before PCR. Polymerase chain reaction accuracy and efficacy were demonstrated by calculating the regression (R2) values of the separate amplification curves. Appropriate antibodies, blocking buffers, and running conditions were established for Western blot, and protein detection and multiplex assays with CypB were performed for each target. During the extraction procedure, the protein phase was dissolved in a modified washing buffer containing 0.1% sodium dodecyl sulfate, followed by ultrafiltration. Enzyme expression on real-time RT-PCR was accomplished with high reliability and reproducibility (R2, 0.990-0.999), and all enzymes except for glutathione peroxidase 1 were detectable in individual retinas on Western blot. Western blot multiplexing with CypB was possible for all targets. In conclusion, connecting gene expression directly to protein levels in the individual rat retina was possible by simultaneous extraction of RNA and protein. Real-time RT-PCR and Western blot allowed accurate detection of retinal protein expressions and levels.

  20. Vaccine strategies against Babesia bovis based on prime-boost immunizations in mice with modified vaccinia Ankara vector and recombinant proteins.

    PubMed

    Jaramillo Ortiz, José Manuel; Del Médico Zajac, María Paula; Zanetti, Flavia Adriana; Molinari, María Paula; Gravisaco, María José; Calamante, Gabriela; Wilkowsky, Silvina Elizabeth

    2014-08-06

    In this study, a recombinant modified vaccinia virus Ankara vector expressing a chimeric multi-antigen was obtained and evaluated as a candidate vaccine in homologous and heterologous prime-boost immunizations with a recombinant protein cocktail. The chimeric multi-antigen comprises immunodominant B and T cell regions of three Babesia bovis proteins. Humoral and cellular immune responses were evaluated in mice to compare the immunogenicity induced by different immunization schemes. The best vaccination scheme was achieved with a prime of protein cocktail and a boost with the recombinant virus. This scheme induced high level of specific IgG antibodies and secreted IFN and a high degree of activation of IFNγ(+) CD4(+) and CD8(+) specific T cells. This is the first report in which a novel vaccine candidate was constructed based on a rationally designed multi-antigen and evaluated in a prime-boost regime, optimizing the immune response necessary for protection against bovine babesiosis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Manganese-dependent carboanhydrase activity of photosystem II proteins.

    PubMed

    Shitov, A V; Pobeguts, O V; Smolova, T N; Allakhverdiev, S I; Klimov, V V

    2009-05-01

    Four sources of carbonic anhydrase (CA) activity in submembrane preparations of photosystem II (PS II) isolated from pea leaves were examined. Three of them belong to the hydrophilic proteins of the oxygen-evolving complex of PS II with molecular mass 33 kDa (protein PsbO), 24 kDa (protein PsbP), and 18 kDa (protein PsbQ). The fourth source of CA activity is associated with a pigment-protein complex of PS II after removing three hydrophilic proteins by salt treatment. Except for protein PsbQ, the CA activity of all these proteins depends on the presence of Mn2+: the purified protein PsbO did not show CA activity before adding Mn2+ into the medium (concentration of Mn2+ required for 50% effect, EC(50), was 670 microM); CA activity of protein mixture composed of PsbP and PsbQ increased more than 5-fold upon adding Mn2+ (EC(50) was 45 microM). CA activity of purified protein PsbP increased 2-fold in the presence of 200 microM Mn2+. As indicated for the mixture of two proteins (PsbP and PsbQ), Mg2+, Ca2+, and Zn2+, in contrast to Mn2+, suppressed CA activity (both initial and Mn2+-induced activity). Since the found sources of CA activity demonstrated properties different from ones of typical CA (need for Mn2+, insensitivity or low sensitivity to acetazolamide or ethoxyzolamide) and such CA activity was found only among PS II proteins, we cannot exclude that they belong to the type of Mn-dependent CA associated with PS II.

  2. Self-focusing and defocusing of Gaussian laser beams in collisional inhomogeneous plasmas with linear density and temperature ramps

    NASA Astrophysics Data System (ADS)

    Hashemzadeh, M.

    2018-01-01

    Self-focusing and defocusing of Gaussian laser beams in collisional inhomogeneous plasmas are investigated in the presence of various laser intensities and linear density and temperature ramps. Considering the ponderomotive force and using the momentum transfer and energy equations, the nonlinear electron density is derived. Taking into account the paraxial approximation and nonlinear electron density, a nonlinear differential equation, governing the focusing and defocusing of the laser beam, is obtained. Results show that in the absence of ramps the laser beam is focused between a minimum and a maximum value of laser intensity. For a certain value of laser intensity and initial electron density, the self-focusing process occurs in a temperature range which reaches its maximum at turning point temperature. However, the laser beam is converged in a narrow range for various amounts of initial electron density. It is indicated that the σ2 parameter and its sign can affect the self-focusing process for different values of laser intensity, initial temperature, and initial density. Finally, it is found that although the electron density ramp-down diverges the laser beam, electron density ramp-up improves the self-focusing process.

  3. Effective intracellular inhibition of the cAMP-dependent protein kinase by microinjection of a modified form of the specific inhibitor peptide PKi in living fibroblasts.

    PubMed

    Fernandez, A; Mery, J; Vandromme, M; Basset, M; Cavadore, J C; Lamb, N J

    1991-08-01

    In order to obtain a peptide retaining its biological activity following microinjection into living cells, we have modified a synthetic peptide [PKi(m)(6-24)], derived from the specific inhibitor protein of the cAMP-dependent protein kinase (A-kinase) in two ways: (1) substitution of the arginine at position 18 for a D-arginine; (2) blockade of the side chain on the C-terminal aspartic acid by a cyclohexyl ester group. In an in vitro assay, PKi(m) has retained a specific inhibitory activity against A-kinase as assessed against six other kinases, with similar efficiency to that of the unmodified PKi(5-24) peptide. Microinjection of PKi(m) into living fibroblasts reveals its capacity to prevent the changes in cell morphology and cytoskeleton induced by drugs which activate endogenous A-kinase, whereas the original PKi peptide failed to do so. This inhibition of A-kinase in vivo by PKi(m) lasts between 4 and 6 h after injection. In light of its effective half-life, this modified peptide opens a route for the use of biologically active peptides in vivo, an approach which has been hampered until now by the exceedingly short half-life of peptides inside living cells. By providing a direct means of inhibiting A-kinase activity for sufficiently long periods to observe effects on cellular functions in living cells, PKi(m) represents a powerful tool in studying the potential role of cAMP-dependent phosphorylation in vivo.

  4. Fractionation, amino acid profiles, antimicrobial and free radical scavenging activities of Citrullus lanatus seed protein.

    PubMed

    Dash, Priyanka; Ghosh, Goutam

    2017-12-01

    In the present study, a modified Osborne fractionation method was followed to isolate albumin (C alb ), globulin (C glo ), prolamin (C pro ) and glutelin (C glu ) successively from seeds of Citrullus lanatus (watermelon). This research work was undertaken to investigate the antimicrobial and antioxidant activities of isolated protein fractions of C. lanatus seed. Amino acid composition and molecular weight distribution were determined to establish their relationship with antimicrobial and antioxidant activity. Among all the fractions, C pro was found to be most effective against A. baumannii followed by C alb and C glo . The results showed that growth of inhibition of these protein fractions differ significantly from each other (p ≤ 0.05). In view of antioxidant potential, C glo exhibited strongest antioxidant capacity while C glu showed weakest antioxidant potential.

  5. Activity-Based Protein Profiling of Microbes

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

    Sadler, Natalie C.; Wright, Aaron T.

    Activity-Based Protein Profiling (ABPP) in conjunction with multimodal characterization techniques has yielded impactful findings in microbiology, particularly in pathogen, bioenergy, drug discovery, and environmental research. Using small molecule chemical probes that react irreversibly with specific proteins or protein families in complex systems has provided insights in enzyme functions in central metabolic pathways, drug-protein interactions, and regulatory protein redox, for systems ranging from photoautotrophic cyanobacteria to mycobacteria, and combining live cell or cell extract ABPP with proteomics, molecular biology, modeling, and other techniques has greatly expanded our understanding of these systems. New opportunities for application of ABPP to microbial systems include:more » enhancing protein annotation, characterizing protein activities in myriad environments, and reveal signal transduction and regulatory mechanisms in microbial systems.« less

  6. Truck accidents at freeway ramps : data analysis and high-risk site identification

    DOT National Transportation Integrated Search

    1998-01-01

    To examine the relationship of ramp design to truck accident rates, this paper presents an analysis of truck accidents in Washington State, plus a comparison to limited data from Colorado and California. The authors group freeway truck accidents by r...

  7. Does Stepwise Voltage Ramping Protect the Kidney from Injury During Extracorporeal Shockwave Lithotripsy? Results of a Prospective Randomized Trial.

    PubMed

    Skuginna, Veronika; Nguyen, Daniel P; Seiler, Roland; Kiss, Bernhard; Thalmann, George N; Roth, Beat

    2016-02-01

    Renal damage is more frequent with new-generation lithotripters. However, animal studies suggest that voltage ramping minimizes the risk of complications following extracorporeal shock wave lithotripsy (SWL). In the clinical setting, the optimal voltage strategy remains unclear. To evaluate whether stepwise voltage ramping can protect the kidney from damage during SWL. A total of 418 patients with solitary or multiple unilateral kidney stones were randomized to receive SWL using a Modulith SLX-F2 lithotripter with either stepwise voltage ramping (n=213) or a fixed maximal voltage (n=205). SWL. The primary outcome was sonographic evidence of renal hematomas. Secondary outcomes included levels of urinary markers of renal damage, stone disintegration, stone-free rate, and rates of secondary interventions within 3 mo of SWL. Descriptive statistics were used to compare clinical outcomes between the two groups. A logistic regression model was generated to assess predictors of hematomas. Significantly fewer hematomas occurred in the ramping group(12/213, 5.6%) than in the fixed group (27/205, 13%; p=0.008). There was some evidence that the fixed group had higher urinary β2-microglobulin levels after SWL compared to the ramping group (p=0.06). Urinary microalbumin levels, stone disintegration, stone-free rate, and rates of secondary interventions did not significantly differ between the groups. The logistic regression model showed a significantly higher risk of renal hematomas in older patients (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.00-1.05; p=0.04). Stepwise voltage ramping was associated with a lower risk of hematomas (OR 0.39, 95% CI 0.19-0.80; p=0.01). The study was limited by the use of ultrasound to detect hematomas. In this prospective randomized study, stepwise voltage ramping during SWL was associated with a lower risk of renal damage compared to a fixed maximal voltage without compromising treatment effectiveness. Lithotripsy is a noninvasive

  8. Implications of sea-level rise in a modern carbonate ramp setting

    NASA Astrophysics Data System (ADS)

    Lokier, Stephen W.; Court, Wesley M.; Onuma, Takumi; Paul, Andreas

    2018-03-01

    This study addresses a gap in our understanding of the effects of sea-level rise on the sedimentary systems and morphological development of recent and ancient carbonate ramp settings. Many ancient carbonate sequences are interpreted as having been deposited in carbonate ramp settings. These settings are poorly-represented in the Recent. The study documents the present-day transgressive flooding of the Abu Dhabi coastline at the southern shoreline of the Arabian/Persian Gulf, a carbonate ramp depositional system that is widely employed as a Recent analogue for numerous ancient carbonate systems. Fourteen years of field-based observations are integrated with historical and recent high-resolution satellite imagery in order to document and assess the onset of flooding. Predicted rates of transgression (i.e. landward movement of the shoreline) of 2.5 m yr- 1 (± 0.2 m yr- 1) based on global sea-level rise alone were far exceeded by the flooding rate calculated from the back-stepping of coastal features (10-29 m yr- 1). This discrepancy results from the dynamic nature of the flooding with increased water depth exposing the coastline to increased erosion and, thereby, enhancing back-stepping. A non-accretionary transgressive shoreline trajectory results from relatively rapid sea-level rise coupled with a low-angle ramp geometry and a paucity of sediments. The flooding is represented by the landward migration of facies belts, a range of erosive features and the onset of bioturbation. Employing Intergovernmental Panel on Climate Change (Church et al., 2013) predictions for 21st century sea-level rise, and allowing for the post-flooding lag time that is typical for the start-up of carbonate factories, it is calculated that the coastline will continue to retrograde for the foreseeable future. Total passive flooding (without considering feedback in the modification of the shoreline) by the year 2100 is calculated to likely be between 340 and 571 m with a flooding rate of 3

  9. Global profiling of proteolytically modified proteins in human metastatic hepatocellular carcinoma cell lines reveals CAPN2 centered network.

    PubMed

    Shen, Chengpin; Yu, Yanyan; Li, Hong; Yan, Guoquan; Liu, Mingqi; Shen, Huali; Yang, Pengyuan

    2012-06-01

    Proteolysis affects every protein at some point in its life cycle. Many biomarkers of disease or cancer are stable proteolytic fragments in biological fluids. There is great interest and a challenge in proteolytically modified protein study to identify physiologic protease-substrate relationships and find potential biomarkers. In this study, two human hepatocellular carcinoma (HCC) cell lines with different metastasis potential, MHCC97L, and HCCLM6, were researched with a high-throughput and sensitive PROTOMAP platform. In total 391 proteins were found to be proteolytically processed and many of them were cleaved into persistent fragments instead of completely degraded. Fragments related to 161 proteins had different expressions in these two cell lines. Through analyzing these significantly changed fragments with bio-informatic tools, several bio-functions such as tumor cell migration and anti-apoptosis were enriched. A proteolysis network was also built up, of which the CAPN2 centered subnetwork, including SPTBN1, ATP5B, and VIM, was more active in highly metastatic HCC cell line. Interestingly, proteolytic modifications of CD44 and FN1 were found to affect their secretion. This work suggests that proteolysis plays an important role in human HCC metastasis. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Non-timber forest products: ramps in the Waynesville, NC watershed

    Treesearch

    Kristina Connor; Jim Chamberlain III; Hilliard Gibbs Jr.; Matt Winn

    2015-01-01

    The potential of forest farming was noted as far back as 1929, but the recognition of its importance dates back only 20 to 30 years. The U.S. market for harvested foods and medicinal plants from forests now exceeds $4 billion annually. Ramps (Allium tricoccum Aiton), or wild leeks, grow in patches in the rich moist forests of the eastern United...

  11. X-ray crystallographic analysis of adipocyte fatty acid binding protein (aP2) modified with 4-hydroxy-2-nonenal

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

    Hellberg, Kristina; Grimsrud, Paul A.; Kruse, Andrew C.

    2012-07-11

    Fatty acid binding proteins (FABP) have been characterized as facilitating the intracellular solubilization and transport of long-chain fatty acyl carboxylates via noncovalent interactions. More recent work has shown that the adipocyte FABP is also covalently modified in vivo on Cys117 with 4-hydroxy-2-nonenal (4-HNE), a bioactive aldehyde linked to oxidative stress and inflammation. To evaluate 4-HNE binding and modification, the crystal structures of adipocyte FABP covalently and noncovalently bound to 4-HNE have been solved to 1.9 {angstrom} and 2.3 {angstrom} resolution, respectively. While the 4-HNE in the noncovalently modified protein is coordinated similarly to a carboxylate of a fatty acid, themore » covalent form show a novel coordination through a water molecule at the polar end of the lipid. Other defining features between the two structures with 4-HNE and previously solved structures of the protein include a peptide flip between residues Ala36 and Lys37 and the rotation of the side chain of Phe57 into its closed conformation. Representing the first structure of an endogenous target protein covalently modified by 4-HNE, these results define a new class of in vivo ligands for FABPs and extend their physiological substrates to include bioactive aldehydes.« less

  12. Mini G protein probes for active G protein-coupled receptors (GPCRs) in live cells.

    PubMed

    Wan, Qingwen; Okashah, Najeah; Inoue, Asuka; Nehmé, Rony; Carpenter, Byron; Tate, Christopher G; Lambert, Nevin A

    2018-05-11

    G protein-coupled receptors (GPCRs) are key signaling proteins that regulate nearly every aspect of cell function. Studies of GPCRs have benefited greatly from the development of molecular tools to monitor receptor activation and downstream signaling. Here, we show that mini G proteins are robust probes that can be used in a variety of assay formats to report GPCR activity in living cells. Mini G (mG) proteins are engineered GTPase domains of Gα subunits that were developed for structural studies of active-state GPCRs. Confocal imaging revealed that mG proteins fused to fluorescent proteins were located diffusely in the cytoplasm and translocated to sites of receptor activation at the cell surface and at intracellular organelles. Bioluminescence resonance energy transfer (BRET) assays with mG proteins fused to either a fluorescent protein or luciferase reported agonist, superagonist, and inverse agonist activities. Variants of mG proteins (mGs, mGsi, mGsq, and mG12) corresponding to the four families of Gα subunits displayed appropriate coupling to their cognate GPCRs, allowing quantitative profiling of subtype-specific coupling to individual receptors. BRET between luciferase-mG fusion proteins and fluorescent markers indicated the presence of active GPCRs at the plasma membrane, Golgi apparatus, and endosomes. Complementation assays with fragments of NanoLuc luciferase fused to GPCRs and mG proteins reported constitutive receptor activity and agonist-induced activation with up to 20-fold increases in luminescence. We conclude that mG proteins are versatile tools for studying GPCR activation and coupling specificity in cells and should be useful for discovering and characterizing G protein subtype-biased ligands. © 2018 Wan et al.

  13. Integration of carboxyl modified magnetic particles and aqueous two-phase extraction for selective separation of proteins.

    PubMed

    Gai, Qingqing; Qu, Feng; Zhang, Tao; Zhang, Yukui

    2011-07-15

    Both of the magnetic particle adsorption and aqueous two-phase extraction (ATPE) were simple, fast and low-cost method for protein separation. Selective proteins adsorption by carboxyl modified magnetic particles was investigated according to protein isoelectric point, solution pH and ionic strength. Aqueous two-phase system of PEG/sulphate exhibited selective separation and extraction for proteins before and after magnetic adsorption. The two combination ways, magnetic adsorption followed by ATPE and ATPE followed by magnetic adsorption, for the separation of proteins mixture of lysozyme, bovine serum albumin, trypsin, cytochrome C and myloglobin were discussed and compared. The way of magnetic adsorption followed by ATPE was also applied to human serum separation. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. RaMP: A Comprehensive Relational Database of Metabolomics Pathways for Pathway Enrichment Analysis of Genes and Metabolites

    PubMed Central

    Zhang, Bofei; Hu, Senyang; Baskin, Elizabeth; Patt, Andrew; Siddiqui, Jalal K.

    2018-01-01

    The value of metabolomics in translational research is undeniable, and metabolomics data are increasingly generated in large cohorts. The functional interpretation of disease-associated metabolites though is difficult, and the biological mechanisms that underlie cell type or disease-specific metabolomics profiles are oftentimes unknown. To help fully exploit metabolomics data and to aid in its interpretation, analysis of metabolomics data with other complementary omics data, including transcriptomics, is helpful. To facilitate such analyses at a pathway level, we have developed RaMP (Relational database of Metabolomics Pathways), which combines biological pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome, WikiPathways, and the Human Metabolome DataBase (HMDB). To the best of our knowledge, an off-the-shelf, public database that maps genes and metabolites to biochemical/disease pathways and can readily be integrated into other existing software is currently lacking. For consistent and comprehensive analysis, RaMP enables batch and complex queries (e.g., list all metabolites involved in glycolysis and lung cancer), can readily be integrated into pathway analysis tools, and supports pathway overrepresentation analysis given a list of genes and/or metabolites of interest. For usability, we have developed a RaMP R package (https://github.com/Mathelab/RaMP-DB), including a user-friendly RShiny web application, that supports basic simple and batch queries, pathway overrepresentation analysis given a list of genes or metabolites of interest, and network visualization of gene-metabolite relationships. The package also includes the raw database file (mysql dump), thereby providing a stand-alone downloadable framework for public use and integration with other tools. In addition, the Python code needed to recreate the database on another system is also publicly available (https://github.com/Mathelab/RaMP-BackEnd). Updates for databases in RaMP will be

  15. RaMP: A Comprehensive Relational Database of Metabolomics Pathways for Pathway Enrichment Analysis of Genes and Metabolites.

    PubMed

    Zhang, Bofei; Hu, Senyang; Baskin, Elizabeth; Patt, Andrew; Siddiqui, Jalal K; Mathé, Ewy A

    2018-02-22

    The value of metabolomics in translational research is undeniable, and metabolomics data are increasingly generated in large cohorts. The functional interpretation of disease-associated metabolites though is difficult, and the biological mechanisms that underlie cell type or disease-specific metabolomics profiles are oftentimes unknown. To help fully exploit metabolomics data and to aid in its interpretation, analysis of metabolomics data with other complementary omics data, including transcriptomics, is helpful. To facilitate such analyses at a pathway level, we have developed RaMP (Relational database of Metabolomics Pathways), which combines biological pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome, WikiPathways, and the Human Metabolome DataBase (HMDB). To the best of our knowledge, an off-the-shelf, public database that maps genes and metabolites to biochemical/disease pathways and can readily be integrated into other existing software is currently lacking. For consistent and comprehensive analysis, RaMP enables batch and complex queries (e.g., list all metabolites involved in glycolysis and lung cancer), can readily be integrated into pathway analysis tools, and supports pathway overrepresentation analysis given a list of genes and/or metabolites of interest. For usability, we have developed a RaMP R package (https://github.com/Mathelab/RaMP-DB), including a user-friendly RShiny web application, that supports basic simple and batch queries, pathway overrepresentation analysis given a list of genes or metabolites of interest, and network visualization of gene-metabolite relationships. The package also includes the raw database file (mysql dump), thereby providing a stand-alone downloadable framework for public use and integration with other tools. In addition, the Python code needed to recreate the database on another system is also publicly available (https://github.com/Mathelab/RaMP-BackEnd). Updates for databases in RaMP will be

  16. Insig proteins mediate feedback inhibition of cholesterol synthesis in the intestine.

    PubMed

    McFarlane, Matthew R; Liang, Guosheng; Engelking, Luke J

    2014-01-24

    Enterocytes are the only cell type that must balance the de novo synthesis and absorption of cholesterol, although the coordinate regulation of these processes is not well understood. Our previous studies demonstrated that enterocytes respond to the pharmacological blockade of cholesterol absorption by ramping up de novo sterol synthesis through activation of sterol regulatory element-binding protein-2 (SREBP-2). Here, we genetically disrupt both Insig1 and Insig2 in the intestine, two closely related proteins that are required for the feedback inhibition of SREBP and HMG-CoA reductase (HMGR). This double knock-out was achieved by generating mice with an intestine-specific deletion of Insig1 using Villin-Cre in combination with a germ line deletion of Insig2. Deficiency of both Insigs in enterocytes resulted in constitutive activation of SREBP and HMGR, leading to an 11-fold increase in sterol synthesis in the small intestine and producing lipidosis of the intestinal crypts. The intestine-derived cholesterol accumulated in plasma and liver, leading to secondary feedback inhibition of hepatic SREBP2 activity. Pharmacological blockade of cholesterol absorption was unable to further induce the already elevated activities of SREBP-2 or HMGR in Insig-deficient enterocytes. These studies confirm the essential role of Insig proteins in the sterol homeostasis of enterocytes.

  17. Insig Proteins Mediate Feedback Inhibition of Cholesterol Synthesis in the Intestine*

    PubMed Central

    McFarlane, Matthew R.; Liang, Guosheng; Engelking, Luke J.

    2014-01-01

    Enterocytes are the only cell type that must balance the de novo synthesis and absorption of cholesterol, although the coordinate regulation of these processes is not well understood. Our previous studies demonstrated that enterocytes respond to the pharmacological blockade of cholesterol absorption by ramping up de novo sterol synthesis through activation of sterol regulatory element-binding protein-2 (SREBP-2). Here, we genetically disrupt both Insig1 and Insig2 in the intestine, two closely related proteins that are required for the feedback inhibition of SREBP and HMG-CoA reductase (HMGR). This double knock-out was achieved by generating mice with an intestine-specific deletion of Insig1 using Villin-Cre in combination with a germ line deletion of Insig2. Deficiency of both Insigs in enterocytes resulted in constitutive activation of SREBP and HMGR, leading to an 11-fold increase in sterol synthesis in the small intestine and producing lipidosis of the intestinal crypts. The intestine-derived cholesterol accumulated in plasma and liver, leading to secondary feedback inhibition of hepatic SREBP2 activity. Pharmacological blockade of cholesterol absorption was unable to further induce the already elevated activities of SREBP-2 or HMGR in Insig-deficient enterocytes. These studies confirm the essential role of Insig proteins in the sterol homeostasis of enterocytes. PMID:24337570

  18. Rapid kinetic BRET measurements to monitor G protein activation by GPCR and non-GPCR proteins.

    PubMed

    Maziarz, Marcin; Garcia-Marcos, Mikel

    2017-01-01

    Heterotrimeric G proteins are central hubs of signal transduction whose activity is controlled by G protein-coupled receptors (GPCRs) as well as by a complex network of regulatory proteins. Recently, bioluminescence resonance energy transfer (BRET)-based assays have been used to monitor real-time activation of heterotrimeric G proteins in cells. Here we describe the use of a previously established BRET assay to monitor G protein activation upon GPCR stimulation and its adaptation to measure G protein activation by non-GPCR proteins, such as by cytoplasmic guanine nucleotide exchange factors (GEFs) like GIV/Girdin. The BRET assay monitors the release of free Gβγ from Gα-Gβγ heterotrimers as a readout of G protein activation, which is readily observable upon agonist stimulation of GPCRs. To control the signal input for non-GPCR activators, we describe the use of a chemically induced dimerization strategy to promote rapid membrane translocation of proteins containing the Gα-binding and -activating (GBA) motif found in some nonreceptor GEFs. The assay described here allows the kinetic measurement of G protein activation with subsecond temporal resolution and to compare the levels of activation induced by GPCR agonists vs those induced by the membrane recruitment of nonreceptor G protein signaling activators. © 2017 Elsevier Inc. All rights reserved.

  19. Control of a Normal Shock Boundary Layer Interaction with Ramped Vanes of Various Sizes

    NASA Astrophysics Data System (ADS)

    Lee, Sang; Loth, Eric

    2017-11-01

    A novel vortex generator design positioned upstream of a normal shock and a subsequent diffuser was investigated using large eddy simulations. In particular, ``ramped-vane'' flow control devices with three difference heights relative to the incoming boundary layer thickness (0.34 δ 0.52 δ and 0.75 δ were placed in a supersonic boundary layer with a freestream Mach number of 1.3 and a Reynolds number of 2,400 based on momentum thickness. These devices are similar to subsonic vanes but are designed to be more mechanically robust while having low wave drag. The devices generated strong streamwise vortices that entrained high momentum fluid to the near-wall region and increased turbulent mixing. The devices also decreased shock-induced flow separation, which resulted in a higher downstream skin friction in the diffuser. In general, the largest ramped-vane (0.75 δ) produced the largest reductions in flow separation, shape factor and overall unsteadiness. However, the medium-sized ramped vane (0.52 δ) was able to also reduce both the separation area and the diffuser displacement thickness. The smallest device (0.34 δ) had a weak impact of the flow in the diffuser, though a 10% reduction in the shape factor was achieved.

  20. Ramp - Metering Algorithms Evaluated within Simplified Conditions

    NASA Astrophysics Data System (ADS)

    Janota, Aleš; Holečko, Peter; Gregor, Michal; Hruboš, Marián

    2017-12-01

    Freeway networks reach their limits, since it is usually impossible to increase traffic volumes by indefinitely extending transport infrastructure through adding new traffic lanes. One of the possible solutions is to use advanced intelligent transport systems, particularly ramp metering systems. The paper shows how two particular algorithms of local and traffic-responsive control (Zone, ALINEA) can be adapted to simplified conditions corresponding to Slovak freeways. Both control strategies are modelled and simulated using PTV Vissim software, including the module VisVAP. Presented results demonstrate the properties of both control strategies, which are compared mutually as well as with the initial situation in which no control strategy is applied

  1. NASA #801 and NASA 7 on ramp

    NASA Technical Reports Server (NTRS)

    1997-01-01

    NASA N801NA and NASA 7 together on the NASA Dryden ramp. The Beechcraft Beech 200 Super KingAir aircraft N7NA, known as NASA 7, has been a support aircraft for many years, flying 'shuttle' missions to Ames Research Center. It once flew from the Jet Propulsion Laboratory and back each day but now (2001) flies between the Dryden Flight Research Center and Ames. A second Beechcraft Beech 200 Super King Air, N701NA, redesignated N801NA, transferred to Dryden on 3 Oct. 1997 and is used for research missions but substitutes for NASA 7 on shuttle missions when NASA 7 is not available.

  2. XB-70A during startup and ramp taxi

    NASA Technical Reports Server (NTRS)

    1968-01-01

    The XB-70 was the world's largest experimental aircraft. Capable of flight at speeds of three times the speed of sound (2,000 miles per hour) at altitudes of 70,000 feet, the XB-70 was used to collect in-flight information for use in the design of future supersonic aircraft, military and civilian. This 35-second video shows the startup of the XB-70A airplane engines, the beginning of its taxi to the runway, and a turn on the ramp that shows the unique configuration of this aircraft.

  3. Mps1 is SUMO-modified during the cell cycle

    PubMed Central

    Chen, Changyan; Lu, Lou; Dai, Wei

    2016-01-01

    Mps1 is a dual specificity protein kinase that regulates the spindle assembly checkpoint and mediates proper microtubule attachment to chromosomes during mitosis. However, the molecular mechanism that controls Mps1 protein level and its activity during the cell cycle remains unclear. Given that sumoylation plays an important role in mitotic progression, we investigated whether Mps1 was SUMO-modified and whether sumoylation affects its activity in mitosis. Our results showed that Mps1 was sumoylated in both asynchronized and mitotic cell populations. Mps1 was modified by both SUMO-1 and SUMO-2. Our further studies revealed that lysine residues including K71, K287, K367 and K471 were essential for Mps1 sumoylation. Sumoylation appeared to play a role in mediating kinetochore localization of Mps1, thus affecting normal mitotic progression. Furthermore, SUMO-resistant mutants of Mps1 interacted with BubR1 more efficiently than it did with the wild-type control. Combined, our results indicate that Mps1 is SUMO-modified that plays an essential role in regulating Mps1 functions during mitosis. PMID:26675261

  4. Mps1 is SUMO-modified during the cell cycle.

    PubMed

    Restuccia, Agnese; Yang, Feikun; Chen, Changyan; Lu, Lou; Dai, Wei

    2016-01-19

    Mps1 is a dual specificity protein kinase that regulates the spindle assembly checkpoint and mediates proper microtubule attachment to chromosomes during mitosis. However, the molecular mechanism that controls Mps1 protein level and its activity during the cell cycle remains unclear. Given that sumoylation plays an important role in mitotic progression, we investigated whether Mps1 was SUMO-modified and whether sumoylation affects its activity in mitosis. Our results showed that Mps1 was sumoylated in both asynchronized and mitotic cell populations. Mps1 was modified by both SUMO-1 and SUMO-2. Our further studies revealed that lysine residues including K71, K287, K367 and K471 were essential for Mps1 sumoylation. Sumoylation appeared to play a role in mediating kinetochore localization of Mps1, thus affecting normal mitotic progression. Furthermore, SUMO-resistant mutants of Mps1 interacted with BubR1 more efficiently than it did with the wild-type control. Combined, our results indicate that Mps1 is SUMO-modified that plays an essential role in regulating Mps1 functions during mitosis.

  5. Microsecond ramp compression of a metallic liner driven by a 5 MA current on the SPHINX machine using a dynamic load current multiplier pulse shaping

    NASA Astrophysics Data System (ADS)

    d'Almeida, T.; Lassalle, F.; Morell, A.; Grunenwald, J.; Zucchini, F.; Loyen, A.; Maysonnave, T.; Chuvatin, A. S.

    2013-09-01

    SPHINX is a 6 MA, 1-μs Linear Transformer Driver (LTD) operated by the CEA Gramat (France) and primarily used for imploding Z-pinch loads for radiation effects studies. Among the options that are currently being evaluated to improve the generator performances are an upgrade to a 20 MA, 1-μs LTD machine and various power amplification schemes, including a compact Dynamic Load Current Multiplier (DLCM). A method for performing magnetic ramp compression experiments, without modifying the generator operation scheme, was developed using the DLCM to shape the initial current pulse in order to obtain the desired load current profile. In this paper, we discuss the overall configuration that was selected for these experiments, including the choice of a coaxial cylindrical geometry for the load and its return current electrode. We present both 3-D Magneto-hydrodynamic and 1D Lagrangian hydrodynamic simulations which helped guide the design of the experimental configuration. Initial results obtained over a set of experiments on an aluminium cylindrical liner, ramp-compressed to a peak pressure of 23 GPa, are presented and analyzed. Details of the electrical and laser Doppler interferometer setups used to monitor and diagnose the ramp compression experiments are provided. In particular, the configuration used to field both homodyne and heterodyne velocimetry diagnostics in the reduced access available within the liner's interior is described. Current profiles measured at various critical locations across the system, particularly the load current, enabled a comprehensive tracking of the current circulation and demonstrate adequate pulse shaping by the DLCM. The liner inner free surface velocity measurements obtained from the heterodyne velocimeter agree with the hydrocode results obtained using the measured load current as the input. An extensive hydrodynamic analysis is carried out to examine information such as pressure and particle velocity history profiles or magnetic

  6. Microsecond ramp compression of a metallic liner driven by a 5 MA current on the SPHINX machine using a dynamic load current multiplier pulse shaping

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

    D'Almeida, T.; Lassalle, F.; Morell, A.

    SPHINX is a 6 MA, 1-μs Linear Transformer Driver (LTD) operated by the CEA Gramat (France) and primarily used for imploding Z-pinch loads for radiation effects studies. Among the options that are currently being evaluated to improve the generator performances are an upgrade to a 20 MA, 1-μs LTD machine and various power amplification schemes, including a compact Dynamic Load Current Multiplier (DLCM). A method for performing magnetic ramp compression experiments, without modifying the generator operation scheme, was developed using the DLCM to shape the initial current pulse in order to obtain the desired load current profile. In this paper,more » we discuss the overall configuration that was selected for these experiments, including the choice of a coaxial cylindrical geometry for the load and its return current electrode. We present both 3-D Magneto-hydrodynamic and 1D Lagrangian hydrodynamic simulations which helped guide the design of the experimental configuration. Initial results obtained over a set of experiments on an aluminium cylindrical liner, ramp-compressed to a peak pressure of 23 GPa, are presented and analyzed. Details of the electrical and laser Doppler interferometer setups used to monitor and diagnose the ramp compression experiments are provided. In particular, the configuration used to field both homodyne and heterodyne velocimetry diagnostics in the reduced access available within the liner's interior is described. Current profiles measured at various critical locations across the system, particularly the load current, enabled a comprehensive tracking of the current circulation and demonstrate adequate pulse shaping by the DLCM. The liner inner free surface velocity measurements obtained from the heterodyne velocimeter agree with the hydrocode results obtained using the measured load current as the input. An extensive hydrodynamic analysis is carried out to examine information such as pressure and particle velocity history profiles or

  7. Evaluation of ground mounted diagrammatic entrance ramp approach signs : final report, October 2000.

    DOT National Transportation Integrated Search

    2000-10-01

    Highway-freeway interchanges can be a source of confusion to unfamiliar drivers. Typically, freeway entrance ramp : information is provided by means of trailblazer assemblies (interstate or highway shield, cardinal direction, and a small : white arro...

  8. Mitogen-Activated Protein Kinase Phosphatase 1 Disrupts Proinflammatory Protein Synthesis in Endotoxin-Adapted Monocytes

    PubMed Central

    Brudecki, Laura; Ferguson, Donald A.; McCall, Charles E.

    2013-01-01

    Autotoxic production of proinflammatory mediators during early sepsis induces excessive inflammation, and their later suppression may limit the immune response. We previously reported that sepsis differentially represses transcription and translation of tumor necrosis factor alpha (TNF-α) and interleukin 1β (IL-1β) to reprogram sepsis inflammation. This switch is gene specific and plays a crucial role in the clinically relevant syndrome of endotoxin adaptation/tolerance, multiorgan failure, and poor sepsis outcome. To further define the mechanisms responsible for translation disruption that follows inflammation induction, we used THP-1 human promonocytes as a model of Toll-like receptor 4 (TLR4) responses found in sepsis. We showed that phosphorylation-dependent activation of p38 mitogen-activated protein kinase (MAPK) and translation disruption of TNF-α and IL-6 follow increased MAPK phosphatase 1 (MKP-1) expression and that MKP-1 knockdown rephosphorylates p38 and restores the capacity to translate TNF-α and IL-6 mRNAs. We also observed that the RNA-binding protein motif 4 (RBM4), a p38 MAPK target, accumulates in an unphosphorylated form in the cytosol in endotoxin-adapted cells, suggesting that dephosphorylated RBM4 may function as a translational repressor. Moreover, MKP-1 knockdown promotes RBM4 phosphorylation, blocks its transfer from the nucleus to the cytosol, and reverses translation repression. We also found that microRNA 146a (miR-146a) knockdown prevents and miR-146a transfection induces MKP-1 expression, which lead to increases or decreases in TNF-α and IL-6 translation, respectively. We conclude that a TLR4-, miR-146a-, p38 MAPK-, and MKP-1-dependent autoregulatory pathway regulates the translation of proinflammatory genes during the acute inflammatory response by spatially and temporally modifying the phosphorylation state of RBM4 translational repressor protein. PMID:23825193

  9. Chaperone activity of human small heat shock protein-GST fusion proteins.

    PubMed

    Arbach, Hannah; Butler, Caley; McMenimen, Kathryn A

    2017-07-01

    Small heat shock proteins (sHsps) are a ubiquitous part of the machinery that maintains cellular protein homeostasis by acting as molecular chaperones. sHsps bind to and prevent the aggregation of partially folded substrate proteins in an ATP-independent manner. sHsps are dynamic, forming an ensemble of structures from dimers to large oligomers through concentration-dependent equilibrium dissociation. Based on structural studies and mutagenesis experiments, it is proposed that the dimer is the smallest active chaperone unit, while larger oligomers may act as storage depots for sHsps or play additional roles in chaperone function. The complexity and dynamic nature of their structural organization has made elucidation of their chaperone function challenging. HspB1 and HspB5 are two canonical human sHsps that vary in sequence and are expressed in a wide variety of tissues. In order to determine the role of the dimer in chaperone activity, glutathione-S-transferase (GST) was genetically linked as a fusion protein to the N-terminus regions of both HspB1 and HspB5 (also known as Hsp27 and αB-crystallin, respectively) proteins in order to constrain oligomer formation of HspB1 and HspB5, by using GST, since it readily forms a dimeric structure. We monitored the chaperone activity of these fusion proteins, which suggest they primarily form dimers and monomers and function as active molecular chaperones. Furthermore, the two different fusion proteins exhibit different chaperone activity for two model substrate proteins, citrate synthase (CS) and malate dehydrogenase (MDH). GST-HspB1 prevents more aggregation of MDH compared to GST-HspB5 and wild type HspB1. However, when CS is the substrate, both GST-HspB1 and GST-HspB5 are equally effective chaperones. Furthermore, wild type proteins do not display equal activity toward the substrates, suggesting that each sHsp exhibits different substrate specificity. Thus, substrate specificity, as described here for full-length GST

  10. Modulation of Active Site Electronic Structure by the Protein Matrix to Control [NiFe] Hydrogenase Reactivity

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

    Smith, Dayle MA; Raugei, Simone; Squier, Thomas C.

    2014-09-30

    Control of the reactivity of the nickel center of the [NiFe] hydrogenase and other metalloproteins commonly involves outer coordination sphere ligands that act to modify the geometry and physical properties of the active site metal centers. We carried out a combined set of classical molecular dynamics and quantum/classical mechanics calculations to provide quantitative estimates of how dynamic fluctuations of the active site within the protein matrix modulate the electronic structure at the catalytic center. Specifically we focused on the dynamics of the inner and outer coordination spheres of the cysteinate-bound Ni–Fe cluster in the catalytically active Ni-C state. There aremore » correlated movements of the cysteinate ligands and the surrounding hydrogen-bonding network, which modulate the electron affinity at the active site and the proton affinity of a terminal cysteinate. On the basis of these findings, we hypothesize a coupling between protein dynamics and electron and proton transfer reactions critical to dihydrogen production.« less

  11. Modulation of active site electronic structure by the protein matrix to control [NiFe] hydrogenase reactivity.

    PubMed

    Smith, Dayle M A; Raugei, Simone; Squier, Thomas C

    2014-11-21

    Control of the reactivity of the nickel center of the [NiFe] hydrogenase and other metalloproteins commonly involves outer coordination sphere ligands that act to modify the geometry and physical properties of the active site metal centers. We carried out a combined set of classical molecular dynamics and quantum/classical mechanics calculations to provide quantitative estimates of how dynamic fluctuations of the active site within the protein matrix modulate the electronic structure at the catalytic center. Specifically we focused on the dynamics of the inner and outer coordination spheres of the cysteinate-bound Ni-Fe cluster in the catalytically active Ni-C state. There are correlated movements of the cysteinate ligands and the surrounding hydrogen-bonding network, which modulate the electron affinity at the active site and the proton affinity of a terminal cysteinate. On the basis of these findings, we hypothesize a coupling between protein dynamics and electron and proton transfer reactions critical to dihydrogen production.

  12. Absolute quantitation of isoforms of post-translationally modified proteins in transgenic organism.

    PubMed

    Li, Yaojun; Shu, Yiwei; Peng, Changchao; Zhu, Lin; Guo, Guangyu; Li, Ning

    2012-08-01

    Post-translational modification isoforms of a protein are known to play versatile biological functions in diverse cellular processes. To measure the molar amount of each post-translational modification isoform (P(isf)) of a target protein present in the total protein extract using mass spectrometry, a quantitative proteomic protocol, absolute quantitation of isoforms of post-translationally modified proteins (AQUIP), was developed. A recombinant ERF110 gene overexpression transgenic Arabidopsis plant was used as the model organism for demonstration of the proof of concept. Both Ser-62-independent (14)N-coded synthetic peptide standards and (15)N-coded ERF110 protein standard isolated from the heavy nitrogen-labeled transgenic plants were employed simultaneously to determine the concentration of all isoforms (T(isf)) of ERF110 in the whole plant cell lysate, whereas a pair of Ser-62-dependent synthetic peptide standards were used to quantitate the Ser-62 phosphosite occupancy (R(aqu)). The P(isf) was finally determined by integrating the two empirically measured variables using the following equation: P(isf) = T(isf) · R(aqu). The absolute amount of Ser-62-phosphorylated isoform of ERF110 determined using AQUIP was substantiated with a stable isotope labeling in Arabidopsis-based relative and accurate quantitative proteomic approach. The biological role of the Ser-62-phosphorylated isoform was demonstrated in transgenic plants.

  13. Design, fabrication, installation and flight service evaluation of a composite cargo ramp skin on a model CH-53 helicopter

    NASA Technical Reports Server (NTRS)

    Lowry, D. W.; Rich, M. J.

    1983-01-01

    The installation of a composite skin panel on the cargo ramp of a CH-530 marine helicopter is discussed. The composite material is of Kevlar/Epoxy (K/E) which replaces aluminum outer skins on the aft two bays of the ramp. The cargo ramp aft region was selected as being a helicopter airframe surface subjected to possible significant field damage and would permit an evaluation of the long term durability of the composite skin panel. A structural analysis was performed and the skin shears determined. Single lap joints of K/E riveted to aluminum were statically tested. The joint tests were used to determine bearing allowables and the required K/E skin gage. The K/E skin panels riveted to aluminum edge members were tested in a shear fixture to confirm the allowable shear and bearing strengths. Impact tests were conducted on aluminum skin panels to determine energy level and damage relationship. The K/E skin panels of various ply orientations and laminate thicknesses were then impacted at similar energy levels. The results of the analysis and tests were used to determine the required K/E skin gages in each of the end two bays of the ramp.

  14. HL-10 on ramp

    NASA Technical Reports Server (NTRS)

    1966-01-01

    The HL-10, seen here parked on the ramp at NASA's Flight Research Center in 1966, had a radically different shape from that of the M2-F2/F3. While the M2s were flat on top and had rounded undersides (giving them a bathtub shape), the HL-10 had a flat lower surface and a rounded top. Both shapes provided lift without wings, however. This photo was taken before the HL-10's fins were modified. The HL-10 was one of five heavyweight lifting-body designs flown at NASA's Flight Research Center (FRC--later Dryden Flight Research Center), Edwards, California, from July 1966 to November 1975 to study and validate the concept of safely maneuvering and landing a low lift-over-drag vehicle designed for reentry from space. Northrop Corporation built the HL-10 and M2-F2, the first two of the fleet of 'heavy' lifting bodies flown by the NASA Flight Research Center. The contract for construction of the HL-10 and the M2-F2 was $1.8 million. 'HL' stands for horizontal landing, and '10' refers to the tenth design studied by engineers at NASA's Langley Research Center, Hampton, Va. After delivery to NASA in January 1966, the HL-10 made its first flight on Dec. 22, 1966, with research pilot Bruce Peterson in the cockpit. The vehicle was unstable and required modifications to its fins to improve its handling qualities and stability. Although an XLR-11 rocket engine was installed in the vehicle, the first 11 drop flights from the B-52 launch aircraft were powerless glide flights to assess handling qualities, stability, and control. In the end, the HL-10 was judged to be the best handling of the three original heavy-weight lifting bodies (M2-F2/F3, HL-10, X-24A). The HL-10 was flown 37 times during the lifting body research program and logged the highest altitude and fastest speed in the Lifting Body program. On Feb. 18, 1970, Air Force test pilot Peter Hoag piloted the HL-10 to Mach 1.86 (1,228 mph). Nine days later, NASA pilot Bill Dana flew the vehicle to 90,030 feet, which became the

  15. Recycling silicon wire-saw slurries: separation of silicon and silicon carbide in a ramp settling tank under an applied electrical field.

    PubMed

    Tsai, Tzu-Hsuan; Shih, Yu-Pei; Wu, Yung-Fu

    2013-05-01

    The growing demand for silicon solar cells in the global market has greatly increased the amount of silicon sawing waste produced each year. Recycling kerf Si and SiC from sawing waste is an economical method to reduce this waste. This study reports the separation of Si and SiC using a ramp settling tank. As they settle in an electrical field, small Si particles with higher negative charges have a longer horizontal displacement than SiC particles in a solution of pH 7, resulting in the separation of Si and SiC. The agreement between experimental results and predicted results shows that the particles traveled a short distance to reach the collection port in the ramp tank. Consequently, the time required for tiny particles to hit the tank bottom decreased, and the interference caused by the dispersion between particles and the fluid motion during settling decreased. In the ramp tank, the highest purities of the collected SiC and Si powders were 95.2 and 7.01 wt%, respectively. Using a ramp tank, the recycling fraction of Si-rich powders (SiC < 15 wt%) reached 22.67% (based on the whole waste). This fraction is greater than that achieved using rectangular tanks. Recycling Si and SiC abrasives from the silicon sawing waste is regarded as an economical solution to reduce the sawing waste. However, the separation of Si and SiC is difficult. This study reports the separation of Si and SiC using a ramp settling tank under an applied electrical field. As they settle in an electrical field, small Si particles with higher negative charges have a longer horizontal displacement than SiC particles in a solution of pH 7, resulting in the separation of Si and SiC. Compared with the rectangular tanks, the recycling fraction of Si-rich powders using a ramp tank is greater, and the proposed ramp settling tank is more suitable for industrial applications.

  16. Application of protein expression profiling to screen chemicals for androgenic activity.

    PubMed

    Hemmer, Michael J; Salinas, Kimberly A; Harris, Peggy S

    2011-05-01

    Protein expression changes can be used for detection of biomarkers that can be applied diagnostically to screen chemicals for endocrine modifying activity. In this study, surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) coupled with a short term fish assay was used to investigate changes in plasma protein expression as a means to screen chemicals for androgenic activity. Adult gravid female sheepshead minnows (Cyprinodon variegatus) were placed into separate aquaria for seawater control, ethanol solvent control, and the following androgen agonist treatments at 5.0μg/L: dihydrotestosterone (DHT), methyldihydrotestosterone (MDHT), testosterone (T), methyltestosterone (MT) and trenbolone (TB). Treatments of 0.6μg/L endosulfan and 40μg/L chlorpyrifos (CP) served as non-androgenic negative stressor controls. Test concentrations were maintained using an intermittent flow-through dosing apparatus supplying exposure water at 20L/h. Fish were sampled at 7 days, the plasma diluted, processed on weak cation exchange CM10 ProteinChip arrays and analyzed. Spectral processing resulted in 249 individual m/z peak clusters for the androgen exposed fish. Partial least squares-discriminant analysis was used to develop an androgen-responsive model using sample spectra from exposures with DHT and unexposed solvent control fish as the training set. The androgen classification model performed with ≥79% specificity (% true negative) and ≥70% sensitivity (% true positive) for non-aromatizable androgens. The aromatizable androgens T and MT were classified as androgenic with specificities of 42 and 79%, respectively. The reduction in sensitivity observed with T is thought to be caused by its metabolic conversion to an estrogen by aromatase. The results of these studies show diagnostic plasma protein expression models can correctly classify chemicals by their androgenic activity using a combination of high throughput mass spectrometry and

  17. Venom Protein C activators as diagnostic agents for defects of protein C System.

    PubMed

    Ramzan, Faiqah; Asmat, Andleeb

    2018-06-18

    Background Protein C is a vitamin K dependent plasma zymogen. It prevents clotting by inhibiting clotting by inactivating factor V and factor VIII. Protein C activation pathway involves three steps: (i) Activation of protein C; (ii) Inhibition of coagulation through inactivating factor V and VIII by activated protein C and (iii) Inhibition of activated protein C by plasma protease inhibitors specific for this enzyme. Proteinases converts the zymogen Protein C (PC) of vertebrates into activated PC, which has been detected in several snake venoms. Most PC activators have been purified from venom of snake species belonging to the genera of the Agkistrodon complex. Unlike the physiological thrombin-catalyzed PC activation reaction which requires thrombomodulin as a cofactor, most snake venom activators directly convert the zymogen PC into the catalytically active form which can easily be determined by means of coagulation or chromogenic substrate techniques. Conclusion The fast-acting PC activator Protac® from Agkistrodon contortrix (southern copperhead snake) venom has been found to have broad application in diagnostic practice for the determination of disorders in the PC pathway. Recently, screening assays for the PC pathway have been introduced, based on the observation that the PC pathway is probably the most important physiological barrier against thrombosis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Poly-Small Ubiquitin-like Modifier (PolySUMO)-binding Proteins Identified through a String Search*

    PubMed Central

    Sun, Huaiyu; Hunter, Tony

    2012-01-01

    Polysumoylation is a crucial cellular response to stresses against genomic integrity or proteostasis. Like the small ubiquitin-like modifier (SUMO)-targeted ubiquitin ligase RNF4, proteins with clustered SUMO-interacting motifs (SIMs) can be important signal transducers downstream of polysumoylation. To identify novel polySUMO-binding proteins, we conducted a computational string search with a custom Python script. We found clustered SIMs in another RING domain protein Arkadia/RNF111. Detailed biochemical analysis of the Arkadia SIMs revealed that dominant SIMs in a SIM cluster often contain a pentameric VIDLT ((V/I/L/F/Y)(V/I)DLT) core sequence that is also found in the SIMs in PIAS family E3s and is likely the best-fitted structure for SUMO recognition. This idea led to the identification of additional novel SIM clusters in FLASH/CASP8AP2, C5orf25, and SOBP/JXC1. We suggest that the clustered SIMs in these proteins form distinct SUMO binding domains to recognize diverse forms of protein sumoylation. PMID:23086935

  19. Tangential blowing for control of strong normal shock - Boundary layer interactions on inlet ramps

    NASA Technical Reports Server (NTRS)

    Schwendemann, M. F.; Sanders, B. W.

    1982-01-01

    The use of tangential blowing from a row of holes in an aft facing step is found to provide good control of the ramp boundary layer, normal shock interaction on a fixed geometry inlet over a wide range of inlet mass flow ratios. Ramp Mach numbers of 1.36 and 1.96 are investigated. The blowing geometry is found to have a significant effect on system performance at the highest Mach number. The use of high-temperature air in the blowing system, however, has only a slight effect on performance. The required blowing rates are significantly high for the most severe test conditions. In addition, the required blowing coefficient is found to be proportional to the normal shock pressure rise.

  20. Matrix-M™ adjuvant enhances immunogenicity of both protein- and modified vaccinia virus Ankara-based influenza vaccines in mice.

    PubMed

    Magnusson, Sofia E; Altenburg, Arwen F; Bengtsson, Karin Lövgren; Bosman, Fons; de Vries, Rory D; Rimmelzwaan, Guus F; Stertman, Linda

    2018-04-01

    Influenza viruses continuously circulate in the human population and escape recognition by virus neutralizing antibodies induced by prior infection or vaccination through accumulation of mutations in the surface proteins hemagglutinin (HA) and neuraminidase (NA). Various strategies to develop a vaccine that provides broad protection against different influenza A viruses are under investigation, including use of recombinant (r) viral vectors and adjuvants. The replication-deficient modified vaccinia virus Ankara (MVA) is a promising vaccine vector that efficiently induces B and T cell responses specific for the antigen of interest. It is assumed that live vaccine vectors do not require an adjuvant to be immunogenic as the vector already mediates recruitment and activation of immune cells. To address this topic, BALB/c mice were vaccinated with either protein- or rMVA-based HA influenza vaccines, formulated with or without the saponin-based Matrix-M™ adjuvant. Co-formulation with Matrix-M significantly increased HA vaccine immunogenicity, resulting in antigen-specific humoral and cellular immune responses comparable to those induced by unadjuvanted rMVA-HA. Of special interest, rMVA-HA immunogenicity was also enhanced by addition of Matrix-M, demonstrated by enhanced HA inhibition antibody titres and cellular immune responses. Matrix-M added to either protein- or rMVA-based HA vaccines mediated recruitment and activation of antigen-presenting cells and lymphocytes to the draining lymph node 24 and 48 h post-vaccination. Taken together, these results suggest that adjuvants can be used not only with protein-based vaccines but also in combination with rMVA to increase vaccine immunogenicity, which may be a step forward to generate new and more effective influenza vaccines.