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Sample records for binding protein-c slow

  1. Myosin Binding Protein-C Slow: a multifaceted family of proteins with a complex expression profile in fast and slow twitch skeletal muscles

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    Maegen A Ackermann

    2013-12-01

    Full Text Available Myosin Binding Protein-C slow (sMyBP-C comprises a complex family of proteins expressed in slow and fast type skeletal muscles. Similar to its fast and cardiac counterparts, sMyBP-C functions to modulate the formation of actomyosin cross-bridges, and to organize and stabilize sarcomeric A- and M-bands. The slow form of MyBP-C was originally classified as a single protein, however several variants encoded by the single MYBPC1 gene have been recently identified. Alternative splicing of the 5’ and 3’ ends of the MYBPC1 transcript has led to the differential expression of small unique segments interspersed between common domains. In addition, the NH2-terminus of sMyBP-C undergoes complex phosphorylation. Thus, alternative splicing and phosphorylation appear to regulate the functional activities of sMyBP-C. sMyBP-C proteins are not restricted to slow twitch muscles, but they are abundantly expressed in fast twitch muscles, too. Using bioinformatic tools, we herein perform a systematic comparison of the known human and mouse sMyBP-C variants. In addition, using single fiber westerns and antibodies to a common region of all known sMyBP-C variants, we present a detailed and comprehensive characterization of the expression profile of sMyBP-C proteins in the slow twitch soleus and the fast twitch flexor digitorum brevis (FDB mouse muscles. Our studies demonstrate for the first time that distinct sMyBP-C variants are co-expressed in the same fiber, and that their expression profile differs among fibers. Given the differential expression of sMyBP-C variants in single fibers, it becomes apparent that each variant or combination thereof may play unique roles in the regulation of actomyosin cross-bridges formation and the stabilization of thick filaments.

  2. Zinc ions bind to and inhibit activated protein C

    DEFF Research Database (Denmark)

    Zhu, Tianqing; Ubhayasekera, Wimal; Nickolaus, Noëlle;

    2010-01-01

    Zn2+ ions were found to efficiently inhibit activated protein C (APC), suggesting a potential regulatory function for such inhibition. APC activity assays employing a chromogenic peptide substrate demonstrated that the inhibition was reversible and the apparent K I was 13 +/- 2 microM. k cat was...... seven fold decreased whereas K M was unaffected in the presence of 10 microM Zn2+. The inhibitory effect of Zn2+ on APC activity was also observed when factor Va was used as a substrate in an assay coupled to a prothrombinase assay. The interaction of Zn2+ with APC was accompanied by a reversible...... fold enhanced, presumably due to the Ca2+-induced conformational change affecting the conformation of the Zn2+-binding site. The inhibition mechanism was non-competitive both in the absence and presence of Ca2+. Comparisons of sequences and structures suggested several possible sites for zinc binding...

  3. Phospholipid Binding Protein C Inhibitor (PCI Is Present on Microparticles Generated In Vitro and In Vivo.

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    Katrin Einfinger

    Full Text Available Protein C inhibitor is a secreted, non-specific serine protease inhibitor with broad protease reactivity. It binds glycosaminoglycans and anionic phospholipids, which can modulate its activity. Anionic phospholipids, such as phosphatidylserine are normally localized to the inner leaflet of the plasma membrane, but are exposed on activated and apoptotic cells and on plasma membrane-derived microparticles. In this report we show by flow cytometry that microparticles derived from cultured cells and activated platelets incorporated protein C inhibitor during membrane blebbing. Moreover, protein C inhibitor is present in/on microparticles circulating in normal human plasma as judged from Western blots, ELISAs, flow cytometry, and mass spectrometry. These plasma microparticles are mainly derived from megakaryocytes. They seem to be saturated with protein C inhibitor, since they do not bind added fluorescence-labeled protein C inhibitor. Heparin partially removed microparticle-bound protein C inhibitor, supporting our assumption that protein C inhibitor is bound via phospholipids. To assess the biological role of microparticle-bound protein C inhibitor we performed protease inhibition assays and co-precipitated putative binding partners on microparticles with anti-protein C inhibitor IgG. As judged from amidolytic assays microparticle-bound protein C inhibitor did not inhibit activated protein C or thrombin, nor did microparticles modulate the activity of exogenous protein C inhibitor. Among the proteins co-precipitating with protein C inhibitor, complement factors, especially complement factor 3, were most striking. Taken together, our data do not support a major role of microparticle-associated protein C inhibitor in coagulation, but rather suggest an interaction with proteins of the complement system present on these phospholipid vesicles.

  4. Severe malaria is associated with parasite binding to endothelial protein C receptor

    DEFF Research Database (Denmark)

    Turner, Louise; Lavstsen, Thomas; Berger, Sanne S;

    2013-01-01

    . falciparum erythrocyte membrane protein 1 (PfEMP1) family and receptors on the endothelial lining. Severe childhood malaria is associated with expression of specific PfEMP1 subtypes containing domain cassettes (DCs) 8 and 13 (ref. 3), but the endothelial receptor for parasites expressing these proteins was...... unknown. Here we identify endothelial protein C receptor (EPCR), which mediates the cytoprotective effects of activated protein C, as the endothelial receptor for DC8 and DC13 PfEMP1. We show that EPCR binding is mediated through the amino-terminal cysteine-rich interdomain region (CIDRα1) of DC8 and...... group A PfEMP1 subfamilies, and that CIDRα1 interferes with protein C binding to EPCR. This PfEMP1 adhesive property links P. falciparum cytoadhesion to a host receptor involved in anticoagulation and endothelial cytoprotective pathways, and has implications for understanding malaria pathology and the...

  5. Protein C Inhibitor (PCI) Binds to Phosphatidylserine Exposing Cells with Implications in the Phagocytosis of Apoptotic Cells and Activated Platelets

    OpenAIRE

    Daniela Rieger; Alice Assinger; Katrin Einfinger; Barbora Sokolikova; Margarethe Geiger

    2014-01-01

    Protein C Inhibitor (PCI) is a secreted serine protease inhibitor, belonging to the family of serpins. In addition to activated protein C PCI inactivates several other proteases of the coagulation and fibrinolytic systems, suggesting a regulatory role in hemostasis. Glycosaminoglycans and certain negatively charged phospholipids, like phosphatidylserine, bind to PCI and modulate its activity. Phosphatidylerine (PS) is exposed on the surface of apoptotic cells and known as a phagocytosis marke...

  6. Computational characterization of the mutation impact on domain C5 of Myosin Binding Protein C

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    Guardiani, Carlo; Cecconi, Fabio; Livi, Roberto

    2007-06-01

    Three mutations of domain C5 of Myosin Binding Protein C are involved in Familial Hypertrophic Cardiomyopathy. We assess their impact through Molecular Dynamics simulations within the framework of a native-centric coarse-grained model. We characterize the clinical relevance of a mutation by: the extent of temperature shift it induces in the unfolding transition, the increase of the kinetic unfolding rates with respect to the wild type, and by \\Fgr-value analysis. Further analysis of folding stages based on the evolution of native contact probabilities reveals an entropy-driven pathway originating in the protein region close to Res115 and ending up in the area of Res28. The mutation of the former residue thus appears to be responsible for an early interruption of the folding process, leaving the protein largely unstructured and yielding a serious impairment of cardiac function. Mut28, on the contrary, thwarts a late stage of folding when the protein is almost completely native-like, leading to a mild phenotype. A bio-informatic analisys of the long and destabilizing CD loop finally shows an excess of negative charge and a low hydrophobicity indicating a possible classification as a natively unfolded sequence. Accordingly, the folding mechanism is suggested to be coupled with binding with a specific ligand.

  7. Novel control of cardiac myofilament response to calcium by S-glutahionylation at specific sites of myosin binding protein C

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    R.JohnSolaro

    2013-11-01

    Full Text Available Our previous studies demonstrated a relation between glutathionylation of cardiac myosin binding protein C and diastolic dysfunction in a hypertensive mouse model stressed by treatment with salt, deoxycorticosterone acetate, and unilateral nephrectomy. Although these results strongly indicated an important role for S-glutathionylation of myosin binding protein C as a modifier of myofilament function, indirect effects of other post-translational modifications may have occurred. Moreover, we did not determine the sites of thiol modification by glutathionylation. To address these issues, we developed an in vitro method to mimic the in situ S-glutathionylation of myofilament proteins and determined direct functional effects and sites of oxidative modification employing Western blotting and mass spectrometry. We induced glutathionylation in vitro by treatment of isolated myofibrils and detergent extracted fiber bundles (skinned fibers with oxidized glutathione (GSSG. Immuno-blotting results revealed increased glutathionylation with GSSG treatment of a protein band around 140 kDa. Using tandem mass spectrometry, we identified the 140 kDa band as cardiac myosin binding protein C and determined the sites of glutathionylation to be at cysteines 655, 479, and 627. Determination of the relation between Ca2+-activation of myofibrillar acto-myosin ATPase rate demonstrated an increased Ca2+-sensitivity induced by the S-glutathionylation. Force generating skinned fiber bundles also showed an increase in Ca-sensitivity when treated with oxidized glutathione, which was reversed with the reducing agent, dithiothreitol. Our data demonstrate that a specific and direct effect of S-glutathionylation of myosin binding protein C is a significant increase in myofilament Ca2+-sensitivity. Our data also provide new insights into the functional significance of oxidative modification of myosin binding protein C and the potential role of domains not previously considered to

  8. Coagulation factor Va binds to human umbilical vein endothelial cells and accelerates protein C activation.

    OpenAIRE

    Maruyama, I.; Salem, H H; Majerus, P W

    1984-01-01

    In vitro the rate of protein C activation by thrombin is significantly accelerated by two distinct cofactors (a) the endothelial cell surface protein, thrombomodulin, and (b) human coagulation Factor Va. We have recently reported that the activity of Factor Va is contained in the 78,000-D light chain. In this study we have investigated the effects of Factor Va and its light chain on the activation of protein C in the presence of cultured endothelial cells. Thrombin-catalyzed protein C activat...

  9. Cloning and characterization of a novel hepatitis B virus core binding protein C12

    Institute of Scientific and Technical Information of China (English)

    Yin-Ying Lu; Jun Cheng; Yong-Ping Yang; Yan Liu; Lin Wang; Ke Li; Ling-Xia Zhang

    2005-01-01

    .CONCLUSION: The novel protein C12 is located in cell plasma, and its overexpression has no significant effect on the metabolism of liver cell. It interacts with many proteins in hepatocytes and may be involved in many processes of gene expression.

  10. Molecular pathology of familial hypertrophic cardiomyopathy caused by mutations in the cardiac myosin binding protein C gene.

    OpenAIRE

    Yu, B.; French, J. A.; Carrier, L.; Jeremy, R W; McTaggart, D R; Nicholson, M R; Hambly, B; Semsarian, C; Richmond, D R; Schwartz, K.; Trent, R.J.

    1998-01-01

    DNA studies in familial hypertrophic cardiomyopathy (FHC) have shown that it is caused by mutations in genes coding for proteins which make up the muscle sarcomere. The majority of mutations in the FHC genes result from missense changes, although one of the most recent genes to be identified (cardiac myosin binding protein C gene, MYBPC3) has predominantly DNA mutations which produce truncated proteins. Both dominant negative and haploinsufficiency models have been proposed to explain the mol...

  11. Myosin-binding protein C displaces tropomyosin to activate cardiac thin filaments and governs their speed by an independent mechanism

    OpenAIRE

    Mun, Ji Young; Previs, Michael J.; Yu, Hope Y.; Gulick, James; Tobacman, Larry S.; Beck Previs, Samantha; Robbins, Jeffrey; Warshaw, David M.; Craig, Roger

    2014-01-01

    Myosin-binding protein C (MyBP-C) is a component of myosin filaments, one of the two sets of contractile elements whose relative sliding is the basis of muscle contraction. In the heart, MyBP-C modulates contractility in response to cardiac stimulation; mutations in MyBP-C lead to cardiac disease. The mechanism by which MyBP-C modulates cardiac contraction is not understood. Using electron microscopy and a light microscopic assay for filament sliding, we demonstrate that MyBP-C binds to the o...

  12. Protein C inhibitor (PCI binds to phosphatidylserine exposing cells with implications in the phagocytosis of apoptotic cells and activated platelets.

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    Daniela Rieger

    Full Text Available Protein C Inhibitor (PCI is a secreted serine protease inhibitor, belonging to the family of serpins. In addition to activated protein C PCI inactivates several other proteases of the coagulation and fibrinolytic systems, suggesting a regulatory role in hemostasis. Glycosaminoglycans and certain negatively charged phospholipids, like phosphatidylserine, bind to PCI and modulate its activity. Phosphatidylerine (PS is exposed on the surface of apoptotic cells and known as a phagocytosis marker. We hypothesized that PCI might bind to PS exposed on apoptotic cells and thereby influence their removal by phagocytosis. Using Jurkat T-lymphocytes and U937 myeloid cells, we show here that PCI binds to apoptotic cells to a similar extent at the same sites as Annexin V, but in a different manner as compared to live cells (defined spots on ∼10-30% of cells. PCI dose dependently decreased phagocytosis of apoptotic Jurkat cells by U937 macrophages. Moreover, the phagocytosis of PS exposing, activated platelets by human blood derived monocytes declined in the presence of PCI. In U937 cells the expression of PCI as well as the surface binding of PCI increased with time of phorbol ester treatment/macrophage differentiation. The results of this study suggest a role of PCI not only for the function and/or maturation of macrophages, but also as a negative regulator of apoptotic cell and activated platelets removal.

  13. 14-3-3 Protein C-terminal stretch occupies ligand binding groove and is displaced by phosphopeptide binding

    Czech Academy of Sciences Publication Activity Database

    Šilhan, J.; Obšilová, V.; Večeř, J.; Herman, P.; Šulc, Miroslav; Teisinger, J.; Obšil, T.

    2004-01-01

    Roč. 279, č. 47 (2004), s. 49113-49119. ISSN 0021-9258 R&D Projects: GA ČR GA204/03/0714; GA ČR GA309/02/1479; GA AV ČR KJB5011308; GA MŠk LZ1K03020 Keywords : 14-3-3 protein * c-terminal * phosphopeptide Subject RIV: EE - Microbiology, Virology Impact factor: 6.355, year: 2004

  14. Human kidney amiloride-binding protein: cDNA structure and functional expression

    International Nuclear Information System (INIS)

    Phenamil, an analog of amiloride, is a potent blocker of the epithelial Naplus channel. It has been used to purify the porcine kidney amiloride-binding protein. Synthetic oligonucleotides derived from partial sequences have been used to screen a human kidney cDNA library and to isolate the cDNA encoding the human amiloride-binding protein. The primary structure was deduced from the DNA sequence analysis. The protein is 713 residues long, with a 19-amino acid signal peptide. The mRNA was expressed in 293-S and NIH 3T3 cells, yielding a glycoprotein (i) that binds amiloride and amiloride analogs with affinities similar to the amiloride receptor associated with the apical Naplus channel in pig kidney membranes and (ii) that is immunoprecipitated with monoclonal antibodies raised against pig kidney amiloride-binding protein

  15. Identification and characterization of amylase binding protein C (AbpC) from Streptococcus mitis NS51

    OpenAIRE

    Vorrasi, John; Chaudhuri, Biswendu; Haase, Elaine M.; Scannapieco, Frank A.

    2010-01-01

    A substantial proportion of the streptococcal species found in dental plaque biofilms are able to interact with the abundant salivary enzyme α-amylase. These streptococci produce proteins that specifically bind amylase. An important plaque species, Streptococcus mitis, secretes a 36-kDa amylase binding protein into the extracellular milieu. Proteins precipitated from S. mitis NS51 cell culture supernatant by the addition of purified salivary amylase were separated by SDS-PAGE, transferred to ...

  16. Doxorubicin-induced carbonylation and degradation of cardiac myosin binding protein C promote cardiotoxicity

    OpenAIRE

    Aryal, Baikuntha; Jeong, Jinsook; Rao, V. Ashutosh

    2014-01-01

    Doxorubicin is one of the most successful anticancer agents. However, 10–30% of all treated patients experience a dose-limiting cardiac adverse event. Oxidative stress is partly responsible for the cardiotoxicity because the heart does not possess required antioxidant mechanisms. Protein oxidation by carbonylation is irreversible and marks proteins for loss of function and degradation. Using proteomics and MS, we identified and investigated cardiac myosin binding protein (MyBPC) as being sele...

  17. S-glutathiolation impairs phosphoregulation and function of cardiac myosin-binding protein C in human heart failure.

    Science.gov (United States)

    Stathopoulou, Konstantina; Wittig, Ilka; Heidler, Juliana; Piasecki, Angelika; Richter, Florian; Diering, Simon; van der Velden, Jolanda; Buck, Friedrich; Donzelli, Sonia; Schröder, Ewald; Wijnker, Paul J M; Voigt, Niels; Dobrev, Dobromir; Sadayappan, Sakthivel; Eschenhagen, Thomas; Carrier, Lucie; Eaton, Philip; Cuello, Friederike

    2016-05-01

    Cardiac myosin-binding protein C (cMyBP-C) regulates actin-myosin interaction and thereby cardiac myocyte contraction and relaxation. This physiologic function is regulated by cMyBP-C phosphorylation. In our study, reduced site-specific cMyBP-C phosphorylation coincided with increased S-glutathiolation in ventricular tissue from patients with dilated or ischemic cardiomyopathy compared to nonfailing donors. We used redox proteomics, to identify constitutive and disease-specific S-glutathiolation sites in cMyBP-C in donor and patient samples, respectively. Among those, a cysteine cluster in the vicinity of the regulatory phosphorylation sites within the myosin S2 interaction domain C1-M-C2 was identified and showed enhanced S-glutathiolation in patients. In vitro S-glutathiolation of recombinant cMyBP-C C1-M-C2 occurred predominantly at Cys(249), which attenuated phosphorylation by protein kinases. Exposure to glutathione disulfide induced cMyBP-C S-glutathiolation, which functionally decelerated the kinetics of Ca(2+)-activated force development in ventricular myocytes from wild-type, but not those from Mybpc3-targeted knockout mice. These oxidation events abrogate protein kinase-mediated phosphorylation of cMyBP-C and therefore potentially contribute to the reduction of its phosphorylation and the contractile dysfunction observed in human heart failure.-Stathopoulou, K., Wittig, I., Heidler, J., Piasecki, A., Richter, F., Diering, S., van der Velden, J., Buck, F., Donzelli, S., Schröder, E., Wijnker, P. J. M., Voigt, N., Dobrev, D., Sadayappan, S., Eschenhagen, T., Carrier, L., Eaton, P., Cuello, F. S-glutathiolation impairs phosphoregulation and function of cardiac myosin-binding protein C in human heart failure. PMID:26839380

  18. Cardiac myosin binding protein C and MAP-kinase activating death domain-containing gene polymorphisms and diastolic heart failure.

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    Cho-Kai Wu

    Full Text Available OBJECTIVE: Myosin binding protein C (MYBPC3 plays a role in ventricular relaxation. The aim of the study was to investigate the association between cardiac myosin binding protein C (MYBPC3 gene polymorphisms and diastolic heart failure (DHF in a human case-control study. METHODS: A total of 352 participants of 1752 consecutive patients from the National Taiwan University Hospital and its affiliated hospital were enrolled. 176 patients diagnosed with DHF confirmed by echocardiography were recruited. Controls were matched 1-to-1 by age, sex, hypertension, diabetes, renal function and medication use. We genotyped 12 single nucleotide polymorphisms (SNPs according to HapMap Han Chinese Beijing databank across a 40 kb genetic region containing the MYBPC3 gene and the neighboring DNA sequences to capture 100% of haplotype variance in all SNPs with minor allele frequencies ≥ 5%. We also analyzed associations of these tagging SNPs and haplotypes with DHF and linkage disequilibrium (LD structure of the MYBPC3 gene. RESULTS: In a single locus analysis, SNP rs2290149 was associated with DHF (allele-specific p = 0.004; permuted p = 0.031. The SNP with a minor allele frequency of 9.4%, had an odds ratio 2.14 (95% CI 1.25-3.66; p = 0.004 for the additive model and 2.06 for the autosomal dominant model (GG+GA : AA, 95% CI 1.17-3.63; p = 0.013, corresponding to a population attributable risk fraction of 12.02%. The haplotypes in a LD block of rs2290149 (C-C-G-C was also significantly associated with DHF (odds ratio 2.10 (1.53-2.89; permuted p = 0.029. CONCLUSIONS: We identified a SNP (rs2290149 among the tagging SNP set that was significantly associated with early DHF in a Chinese population.

  19. Staphylococcus aureus manganese transport protein C (MntC is an extracellular matrix- and plasminogen-binding protein.

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    Natália Salazar

    Full Text Available Infections caused by Staphylococcus aureus--particularly nosocomial infections--represent a great concern. Usually, the early stage of pathogenesis consists on asymptomatic nasopharynx colonization, which could result in dissemination to other mucosal niches or invasion of sterile sites, such as blood. This pathogenic route depends on scavenging of nutrients as well as binding to and disrupting extracellular matrix (ECM. Manganese transport protein C (MntC, a conserved manganese-binding protein, takes part in this infectious scenario as an ion-scavenging factor and surprisingly as an ECM and coagulation cascade binding protein, as revealed in this work. This study showed a marked ability of MntC to bind to several ECM and coagulation cascade components, including laminin, collagen type IV, cellular and plasma fibronectin, plasminogen and fibrinogen by ELISA. The MntC binding to plasminogen appears to be related to the presence of surface-exposed lysines, since previous incubation with an analogue of lysine residue, ε-aminocaproic acid, or increasing ionic strength affected the interaction between MntC and plasminogen. MntC-bound plasminogen was converted to active plasmin in the presence of urokinase plasminogen activator (uPA. The newly released plasmin, in turn, acted in the cleavage of the α and β chains of fibrinogen. In conclusion, we describe a novel function for MntC that may help staphylococcal mucosal colonization and establishment of invasive disease, through the interaction with ECM and coagulation cascade host proteins. These data suggest that this potential virulence factor could be an adequate candidate to compose an anti-staphylococcal human vaccine formulation.

  20. Cytoplasmic poly(A) binding protein C4 serves a critical role in erythroid differentiation.

    Science.gov (United States)

    Kini, Hemant K; Kong, Jian; Liebhaber, Stephen A

    2014-04-01

    The expression of an mRNA is strongly impacted by its 3' poly(A) tail and associated poly(A)-binding proteins (PABPs). Vertebrates encode six PABP isoforms that vary in abundance, distribution, developmental control, and subcellular localization. Here we demonstrate that the minor PABP isoform PABPC4 is expressed in erythroid cells and impacts the steady-state expression of a subset of erythroid mRNAs. Motif analyses reveal a high-value AU-rich motif in the 3' untranslated regions (UTRs) of PABPC4-impacted mRNAs. This motif enhances the association of PABPC4 with mRNAs containing critically shortened poly(A) tails. This association may serve to protect a subset of mRNAs from accelerated decay. Finally, we demonstrate that selective depletion of PABPC4 in an erythroblast cell line inhibits terminal erythroid maturation with corresponding alterations in the erythroid gene expression. These observations lead us to conclude that PABPC4 plays an essential role in posttranscriptional control of a major developmental pathway. PMID:24469397

  1. Cardiac myosin binding protein C phosphorylation affects cross-bridge cycle's elementary steps in a site-specific manner.

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    Li Wang

    Full Text Available Based on our recent finding that cardiac myosin binding protein C (cMyBP-C phosphorylation affects muscle contractility in a site-specific manner, we further studied the force per cross-bridge and the kinetic constants of the elementary steps in the six-state cross-bridge model in cMyBP-C mutated transgenic mice for better understanding of the influence of cMyBP-C phosphorylation on contractile functions. Papillary muscle fibres were dissected from cMyBP-C mutated mice of ADA (Ala273-Asp282-Ala302, DAD (Asp273-Ala282-Asp302, SAS (Ser273-Ala282-Ser302, and t/t (cMyBP-C null genotypes, and the results were compared to transgenic mice expressing wide-type (WT cMyBP-C. Sinusoidal analyses were performed with serial concentrations of ATP, phosphate (Pi, and ADP. Both t/t and DAD mutants significantly reduced active tension, force per cross-bridge, apparent rate constant (2πc, and the rate constant of cross-bridge detachment. In contrast to the weakened ATP binding and enhanced Pi and ADP release steps in t/t mice, DAD mice showed a decreased ADP release without affecting the ATP binding and the Pi release. ADA showed decreased ADP release, and slightly increased ATP binding and cross-bridge detachment steps, whereas SAS diminished the ATP binding step and accelerated the ADP release step. t/t has the broadest effects with changes in most elementary steps of the cross-bridge cycle, DAD mimics t/t to a large extent, and ADA and SAS predominantly affect the nucleotide binding steps. We conclude that the reduced tension production in DAD and t/t is the result of reduced force per cross-bridge, instead of the less number of strongly attached cross-bridges. We further conclude that cMyBP-C is an allosteric activator of myosin to increase cross-bridge force, and its phosphorylation status modulates the force, which is regulated by variety of protein kinases.

  2. Site-directed spectroscopy of cardiac myosin-binding protein C reveals effects of phosphorylation on protein structural dynamics.

    Science.gov (United States)

    Colson, Brett A; Thompson, Andrew R; Espinoza-Fonseca, L Michel; Thomas, David D

    2016-03-22

    We have used the site-directed spectroscopies of time-resolved fluorescence resonance energy transfer (TR-FRET) and double electron-electron resonance (DEER), combined with complementary molecular dynamics (MD) simulations, to resolve the structure and dynamics of cardiac myosin-binding protein C (cMyBP-C), focusing on the N-terminal region. The results have implications for the role of this protein in myocardial contraction, with particular relevance to β-adrenergic signaling, heart failure, and hypertrophic cardiomyopathy. N-terminal cMyBP-C domains C0-C2 (C0C2) contain binding regions for potential interactions with both thick and thin filaments. Phosphorylation by PKA in the MyBP-C motif regulates these binding interactions. Our spectroscopic assays detect distances between pairs of site-directed probes on cMyBP-C. We engineered intramolecular pairs of labeling sites within cMyBP-C to measure, with high resolution, the distance and disorder in the protein's flexible regions using TR-FRET and DEER. Phosphorylation reduced the level of molecular disorder and the distribution of C0C2 intramolecular distances became more compact, with probes flanking either the motif between C1 and C2 or the Pro/Ala-rich linker (PAL) between C0 and C1. Further insight was obtained from microsecond MD simulations, which revealed a large structural change in the disordered motif region in which phosphorylation unmasks the surface of a series of residues on a stable α-helix within the motif with high potential as a protein-protein interaction site. These experimental and computational findings elucidate structural transitions in the flexible and dynamic portions of cMyBP-C, providing previously unidentified molecular insight into the modulatory role of this protein in cardiac muscle contractility. PMID:26908877

  3. The A31P missense mutation in cardiac myosin binding protein C alters protein structure but does not cause haploinsufficiency.

    Science.gov (United States)

    van Dijk, Sabine J; Bezold Kooiker, Kristina; Mazzalupo, Stacy; Yang, Yuanzhang; Kostyukova, Alla S; Mustacich, Debbie J; Hoye, Elaine R; Stern, Joshua A; Kittleson, Mark D; Harris, Samantha P

    2016-07-01

    Mutations in MYBPC3, the gene encoding cardiac myosin binding protein C (cMyBP-C), are a major cause of hypertrophic cardiomyopathy (HCM). While most mutations encode premature stop codons, missense mutations causing single amino acid substitutions are also common. Here we investigated effects of a single proline for alanine substitution at amino acid 31 (A31P) in the C0 domain of cMyBP-C, which was identified as a natural cause of HCM in cats. Results using recombinant proteins showed that the mutation disrupted C0 structure, altered sensitivity to trypsin digestion, and reduced recognition by an antibody that preferentially recognizes N-terminal domains of cMyBP-C. Western blots detecting A31P cMyBP-C in myocardium of cats heterozygous for the mutation showed a reduced amount of A31P mutant protein relative to wild-type cMyBP-C, but the total amount of cMyBP-C was not different in myocardium from cats with or without the A31P mutation indicating altered rates of synthesis/degradation of A31P cMyBP-C. Also, the mutant A31P cMyBP-C was properly localized in cardiac sarcomeres. These results indicate that reduced protein expression (haploinsufficiency) cannot account for effects of the A31P cMyBP-C mutation and instead suggest that the A31P mutation causes HCM through a poison polypeptide mechanism that disrupts cMyBP-C or myocyte function. PMID:26777460

  4. Binding of complement proteins C1q and C4bp to serum amyloid P component (SAP) in solid contra liquid phase

    DEFF Research Database (Denmark)

    Sørensen, Inge Juul; Nielsen, EH; Andersen, Ove; Danielsen, B; Svehag, SE

    1996-01-01

    Serum amyloid P component (SAP), a member of the conserved pentraxin family of plasma proteins, binds calcium dependently to its ligands. The authors investigated SAPs interaction with the complement proteins C4b binding protein (C4bp) and C1q by ELISA, immunoelectrophoresis and electron microscopy...... affinity, did not interfere with the subsequent binding of C4bp or C1q to SAP. In contrast, collagen I and IV showed partial competition with the binding of C1q to SAP. Using fresh serum, immobilized native SAP bound C4bp whereas binding of C1q/C1 could not be demonstrated. Altogether the results indicate...... that firm binding of C1q and C4bp to SAP requires that SAP is presented on a solid phase, that C1q and C4bp react with sites distinct from the heparin binding site, and that C1q and collagen I share binding sites on SAP. Immobilized native SAP, aggregated SAP and SAP-heparansulphate complexes induced...

  5. Myomegalin is a novel A-kinase anchoring protein involved in the phosphorylation of cardiac myosin binding protein C

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    Riedemann Johann

    2011-05-01

    Full Text Available Abstract Background Cardiac contractility is regulated by dynamic phosphorylation of sarcomeric proteins by kinases such as cAMP-activated protein kinase A (PKA. Efficient phosphorylation requires that PKA be anchored close to its targets by A-kinase anchoring proteins (AKAPs. Cardiac Myosin Binding Protein-C (cMyBPC and cardiac troponin I (cTNI are hypertrophic cardiomyopathy (HCM-causing sarcomeric proteins which regulate contractility in response to PKA phosphorylation. Results During a yeast 2-hybrid (Y2H library screen using a trisphosphorylation mimic of the C1-C2 region of cMyBPC, we identified isoform 4 of myomegalin (MMGL as an interactor of this N-terminal cMyBPC region. As MMGL has previously been shown to interact with phosphodiesterase 4D, we speculated that it may be a PKA-anchoring protein (AKAP. To investigate this possibility, we assessed the ability of MMGL isoform 4 to interact with PKA regulatory subunits R1A and R2A using Y2H-based direct protein-protein interaction assays. Additionally, to further elucidate the function of MMGL, we used it as bait to screen a cardiac cDNA library. Other PKA targets, viz. CARP, COMMD4, ENO1, ENO3 and cTNI were identified as putative interactors, with cTNI being the most frequent interactor. We further assessed and confirmed these interactions by fluorescent 3D-co-localization in differentiated H9C2 cells as well as by in vivo co-immunoprecipitation. We also showed that quantitatively more interaction occurs between MMGL and cTNI under β-adrenergic stress. Moreover, siRNA-mediated knockdown of MMGL leads to reduction of cMyBPC levels under conditions of adrenergic stress, indicating that MMGL-assisted phosphorylation is requisite for protection of cMyBPC against proteolytic cleavage. Conclusions This study ascribes a novel function to MMGL isoform 4: it meets all criteria for classification as an AKAP, and we show that is involved in the phosphorylation of cMyBPC as well as cTNI, hence MMGL

  6. Double heterozygosity for mutations in the β-myosin heavy chain and in the cardiac myosin binding protein C genes in a family with hypertrophic cardiomyopathy

    OpenAIRE

    Richard, P.; Isnard, R.; Carrier, L.; Dubourg, O.; Donatien, Y.; Mathieu, B.; Bonne, G.; Gary, F; Charron, P; HAGEGE, A.; Komajda, M; Schwartz, K.; Hainque, B

    1999-01-01

    Familial hypertrophic cardiomyopathy is a genetically heterogeneous autosomal dominant disease, caused by mutations in several sarcomeric protein genes. So far, seven genes have been shown to be associated with the disease with the β-myosin heavy chain (MYH7) and the cardiac myosin binding protein C (MYBPC3) genes being the most frequently involved.
We performed electrocardiography (ECG) and echocardiography in 15 subjects with hypertrophic cardiomyopathy from a French Caribbean family. Genet...

  7. Interaction between Endothelial Protein C Receptor and Intercellular Adhesion Molecule 1 to Mediate Binding of Plasmodium falciparum-Infected Erythrocytes to Endothelial Cells

    Science.gov (United States)

    Avril, Marion; Bernabeu, Maria; Benjamin, Maxwell; Brazier, Andrew Jay

    2016-01-01

    ABSTRACT Intercellular adhesion molecule 1 (ICAM-1) and the endothelial protein C receptor (EPCR) are candidate receptors for the deadly complication cerebral malaria. However, it remains unclear if Plasmodium falciparum parasites with dual binding specificity are involved in cytoadhesion or different parasite subpopulations bind in brain microvessels. Here, we investigated this issue by studying different subtypes of ICAM-1-binding parasite lines. We show that two parasite lines expressing domain cassette 13 (DC13) of the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family have dual binding specificity for EPCR and ICAM-1 and further mapped ICAM-1 binding to the first DBLβ domain following the PfEMP1 head structure in both proteins. As PfEMP1 head structures have diverged between group A (EPCR binders) and groups B and C (CD36 binders), we also investigated how ICAM-1-binding parasites with different coreceptor binding traits influence P. falciparum-infected erythrocyte binding to endothelial cells. Whereas levels of binding to tumor necrosis factor alpha (TNF-α)-stimulated endothelial cells from the lung and brain by all ICAM-1-binding parasite lines increased, group A (EPCR and ICAM-1) was less dependent than group B (CD36 and ICAM-1) on ICAM-1 upregulation. Furthermore, both group A DC13 parasite lines had higher binding levels to brain endothelial cells (a microvascular niche with limited CD36 expression). This study shows that ICAM-1 is a coreceptor for a subset of EPCR-binding parasites and provides the first evidence of how EPCR and ICAM-1 interact to mediate parasite binding to both resting and TNF-α-activated primary brain and lung endothelial cells. PMID:27406562

  8. Genotype-phenotype correlation between the cardiac myosin binding protein C mutation A31P and hypertrophic cardiomyopathy in a cohort of Maine Coon cats

    DEFF Research Database (Denmark)

    Granström, S; Godiksen, M T N; Christiansen, M;

    2015-01-01

    OBJECTIVES: A missense mutation (A31P) in the cardiac myosin binding protein C gene has been associated with hypertrophic cardiomyopathy (HCM) in Maine Coon cats. The aim of this study was to investigate the effect of A31P on development of HCM, myocardial diastolic dysfunction detected by color...... tissue Doppler imaging and occurrence of cardiac death during longitudinal follow-up in a cohort of Maine Coon cats. ANIMALS: The original cohort comprised 282 cats (158 of wild-type genotype, 99 heterozygous for A31P and 25 homozygous for A31P). METHODS: Prospective longitudinal study including...... echocardiography and registration of survival. RESULTS: The median age at the initial examination was 1.7 years (range, 0.8-9.2 years) and 6.4% (18/282) of the cats were diagnosed with HCM. One hundred sixty-five cats were eligible for echocardiographic re-examination, and during an average follow-up period of 2...

  9. Polyglutamylated Tubulin Binding Protein C1orf96/CSAP Is Involved in Microtubule Stabilization in Mitotic Spindles

    Science.gov (United States)

    Ohta, Shinya; Hamada, Mayako; Sato, Nobuko; Toramoto, Iyo

    2015-01-01

    The centrosome-associated C1orf96/Centriole, Cilia and Spindle-Associated Protein (CSAP) targets polyglutamylated tubulin in mitotic microtubules (MTs). Loss of CSAP causes critical defects in brain development; however, it is unclear how CSAP association with MTs affects mitosis progression. In this study, we explored the molecular mechanisms of the interaction of CSAP with mitotic spindles. Loss of CSAP caused MT instability in mitotic spindles and resulted in mislocalization of Nuclear protein that associates with the Mitotic Apparatus (NuMA), with defective MT dynamics. Thus, CSAP overload in the spindles caused extensive MT stabilization and recruitment of NuMA. Moreover, MT stabilization by CSAP led to high levels of polyglutamylation on MTs. MT depolymerization by cold or nocodazole treatment was inhibited by CSAP binding. Live-cell imaging analysis suggested that CSAP-dependent MT-stabilization led to centrosome-free MT aster formation immediately upon nuclear envelope breakdown without γ-tubulin. We therefore propose that CSAP associates with MTs around centrosomes to stabilize MTs during mitosis, ensuring proper bipolar spindle formation and maintenance. PMID:26562023

  10. Human translocation liposarcoma-CCAAT/enhancer binding protein (C/EBP) homologous protein (TLS-CHOP) oncoprotein prevents adipocyte differentiation by directly interfering with C/EBPbeta function.

    Science.gov (United States)

    Adelmant, G; Gilbert, J D; Freytag, S O

    1998-06-19

    Human translocation liposarcoma (TLS)-CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP) is a fusion oncoprotein found specifically in a malignant tumor of adipose tissue and results from a t(12;16) translocation that fuses the amino-terminal part of TLS to the entire coding region of CHOP. Being that CHOP is a member of the C/EBP transcription factor family, proteins that comprise part of the adipocyte differentiation machinery, we examined whether TLS-CHOP blocked adipocyte differentiation by directly interfering with C/EBP function. Using a single-step retroviral infection protocol, either wild-type or mutant TLS-CHOP were co-expressed along with C/EBPbeta in naïve NIH3T3 cells, and their ability to inhibit C/EBPbeta-driven adipogenesis was determined. TLS-CHOP was extremely effective at blocking adipocyte differentiation when expressed at a level comparable to that observed in human myxoid liposarcoma. This effect of TLS-CHOP required a functional leucine zipper domain and correlated with its ability to heterodimerize with C/EBPbeta and inhibit C/EBPbeta DNA binding and transactivation activity in situ. In contrast, the TLS-CHOP basic region was dispensable, making it unlikely that the inhibitory effect of TLS-CHOP is attributable to unscheduled gene expression resulting from TLS-CHOP's putative transactivation activity. Another adipogenic transcription factor, PPARgamma2, was able to rescue TLS-CHOP-inhibited cells, indicating that TLS-CHOP interferes primarily with C/EBPbeta-driven adipogenesis and not with other requisite events of the adipocyte differentiation program. Together, the results demonstrate that TLS-CHOP blocks adipocyte differentiation by directly preventing C/EBPbeta from binding to and transactivating its target genes. Moreover, they provide strong support for the thesis that a blockade to normal differentiation is an important aspect of the cancer process. PMID:9624148

  11. The CCAAT/enhancer binding protein (C/EBP δ is differently regulated by fibrillar and oligomeric forms of the Alzheimer amyloid-β peptide

    Directory of Open Access Journals (Sweden)

    Nilsson Lars NG

    2011-04-01

    Full Text Available Abstract Background The transcription factors CCAAT/enhancer binding proteins (C/EBP α, β and δ have been shown to be expressed in brain and to be involved in regulation of inflammatory genes in concert with nuclear factor κB (NF-κB. In general, C/EBPα is down-regulated, whereas both C/EBPβ and δ are up-regulated in response to inflammatory stimuli. In Alzheimer's disease (AD one of the hallmarks is chronic neuroinflammation mediated by astrocytes and microglial cells, most likely induced by the formation of amyloid-β (Aβ deposits. The inflammatory response in AD has been ascribed both beneficial and detrimental roles. It is therefore important to delineate the inflammatory mediators and signaling pathways affected by Aβ deposits with the aim of defining new therapeutic targets. Methods Here we have investigated the effects of Aβ on expression of C/EBP family members with a focus on C/EBPδ in rat primary astro-microglial cultures and in a transgenic mouse model with high levels of fibrillar Aβ deposits (tg-ArcSwe by western blot analysis. Effects on DNA binding activity were analyzed by electrophoretic mobility shift assay. Cross-talk between C/EBPδ and NF-κB was investigated by analyzing binding to a κB site using a biotin streptavidin-agarose pull-down assay. Results We show that exposure to fibril-enriched, but not oligomer-enriched, preparations of Aβ inhibit up-regulation of C/EBPδ expression in interleukin-1β-activated glial cultures. Furthermore, we observed that, in aged transgenic mice, C/EBPα was significantly down-regulated and C/EBPβ was significantly up-regulated. C/EBPδ, on the other hand, was selectively down-regulated in the forebrain, a part of the brain showing high levels of fibrillar Aβ deposits. In contrast, no difference in expression levels of C/EBPδ between wild type and transgenic mice was detected in the relatively spared hindbrain. Finally, we show that interleukin-1β-induced C/EBPδ DNA

  12. Role of DNA binding sites and slow unbinding kinetics in titration-based oscillators

    Science.gov (United States)

    Karapetyan, Sargis; Buchler, Nicolas E.

    2015-12-01

    Genetic oscillators, such as circadian clocks, are constantly perturbed by molecular noise arising from the small number of molecules involved in gene regulation. One of the strongest sources of stochasticity is the binary noise that arises from the binding of a regulatory protein to a promoter in the chromosomal DNA. In this study, we focus on two minimal oscillators based on activator titration and repressor titration to understand the key parameters that are important for oscillations and for overcoming binary noise. We show that the rate of unbinding from the DNA, despite traditionally being considered a fast parameter, needs to be slow to broaden the space of oscillatory solutions. The addition of multiple, independent DNA binding sites further expands the oscillatory parameter space for the repressor-titration oscillator and lengthens the period of both oscillators. This effect is a combination of increased effective delay of the unbinding kinetics due to multiple binding sites and increased promoter ultrasensitivity that is specific for repression. We then use stochastic simulation to show that multiple binding sites increase the coherence of oscillations by mitigating the binary noise. Slow values of DNA unbinding rate are also effective in alleviating molecular noise due to the increased distance from the bifurcation point. Our work demonstrates how the number of DNA binding sites and slow unbinding kinetics, which are often omitted in biophysical models of gene circuits, can have a significant impact on the temporal and stochastic dynamics of genetic oscillators.

  13. Analysis of slow-binding enzyme inhibitors at elevated enzyme concentrations.

    Science.gov (United States)

    Perdicakis, Basil; Montgomery, Heather J; Guillemette, J Guy; Jervis, Eric

    2005-02-15

    The improvement in the characterization of slow-binding inhibitors achieved by performing experiments at elevated enzyme concentrations is presented. In particular, the characterization of slow-binding inhibitors conforming to a two-step mode of inhibition with a steady-state dissociation constant that is much lower than the initial dissociation constant with enzyme is discussed. For these systems, inhibition is rapid and low steady-state product concentrations are produced at saturating inhibitor concentrations. By working at elevated enzyme concentrations, improved signal-to-noise ratios are achieved and data may be collected at saturating inhibitor levels. Numerical simulations confirmed that improved parameter estimates are obtained and useful data to discern the mechanism of slow-binding inhibition are produced by working at elevated enzyme concentrations. The saturation kinetics that were unobservable in two previous studies of an enzyme inhibitor system were measured by performing experiments at an elevated enzyme concentration. These results indicate that consideration of the quality of the data acquired using a particular assay is an important factor when selecting the enzyme concentration at which to perform experiments used to characterize the class of enzyme inhibitors examined herein. PMID:15691501

  14. The role of DNA binding sites and slow unbinding kinetics in titration-based oscillators

    CERN Document Server

    Karapetyan, Sargis

    2015-01-01

    Genetic oscillators, such as circadian clocks, are constantly perturbed by molecular noise arising from the small number of molecules involved in gene regulation. One of the strongest sources of stochasticity is the binary noise that arises from the binding of a regulatory protein to a promoter in the chromosomal DNA. In this study, we focus on two minimal oscillators based on activator titration and repressor titration to understand the key parameters that are important for oscillations and for overcoming binary noise. We show that the rate of unbinding from the DNA, despite traditionally being considered a fast parameter, needs to be slow to broaden the space of oscillatory solutions. The addition of multiple, independent DNA binding sites further expands the oscillatory parameter space for the repressor-titration oscillator and lengthens the period of both oscillators. This effect is a combination of increased effective delay of the unbinding kinetics due to multiple binding sites and increased promoter ul...

  15. Ammonoxidised lignins as slow nitrogen-releasing soil amendments and CO₂-binding matrix.

    Science.gov (United States)

    Liebner, Falk; Pour, Georg; de la Rosa Arranz, José Maria; Hilscher, André; Rosenau, Thomas; Knicker, Heike

    2011-09-01

    Nitrogen (N) is a major nutrient element controlling the cycling of organic matter in the biosphere. Its availability in soils is closely related to biological productivity. In order to reduce the negative environmental impact, associated with the application of mineral N-fertilizers, the use of ammonoxidised technical lignins is suggested. They can act as potential slow N-release fertilisers which concomitantly may increase C sequestration of soils by its potential to bind CO₂. The idea of our study was to combine an improved chemical characterisation of ammonoxidised ligneous matter as well as their CO₂-binding potential, with laboratory pot experiments, performed to enable an evaluation of their behaviour and stability during the biochemical reworking occurring in active soils. PMID:22022715

  16. Nickel-specific, slow-binding inhibition of carbon monoxide dehydrogenase from Rhodospirillum rubrum by cyanide

    International Nuclear Information System (INIS)

    The inhibition of purified carbon monoxide dehydrogenase from Rhodospirillum rubrum by cyanide was investigated in both the presence and absence of CO and electron acceptor. The inhibition was a time-dependent process exhibiting pseudo-first-order kinetics under both sets of conditions. The true second-order rate constants for inhibition were 72.2 M-1 s-1 with both substrates present and 48.9 and 79.5 M-1 s-1, respectively, for the reduced and oxidized enzymes incubated with cyanide. CO partially protected the enzyme against inhibition after 25-min incubation with 100 μM KCN. Dissociation constants of 8.46 μM (KCN) and 4.70 μM (CO) were calculated for the binding of cyanide and CO to the enzyme. Cyanide inhibition was fully reversible under an atmosphere of CO after removal of unbound cyanide. N2 was unable to reverse the inhibition. The competence of nickel-deficient (apo) CO dehydrogenase to undergo activation by NiCl2 was unaffected by prior incubation with cyanide. Cyanide inhibition of holo-CO dehydrogenase was not reversed by addition of NiCl2. 14CN- remained associated with holoenzyme but not with apoenzyme through gel filtration chromatography. These findings suggest that cyanide is a slow-binding, active-site-directed, nickel-specific, reversible inhibitor of CO dehydrogenase. The authors propose that cyanide inhibits CO dehydrogenase by being a analogue of CO and by binding through enzyme-bound nickel

  17. Slow-binding inhibition of 2-keto-3-deoxy-6-phosphogluconate (KDPG) aldolase.

    Science.gov (United States)

    Braga, Rémi; Hecquet, Laurence; Blonski, Casimir

    2004-06-01

    2-Keto-3-deoxy-6-phosphogluconate (KDPG) aldolase is a key enzyme in the Entner-Doudoroff pathway of bacteria. It catalyzes the reversible production of KDPG from pyruvate and D-glyceraldehyde 3-phosphate through a class I Schiff base mechanism. On the basis of aldolase mechanistic pathway, various pyruvate analogues bearing beta-diketo structures were designed and synthesized as potential inhibitors. Their capacity to inhibit aldolase catalyzed reaction by forming stabilized iminium ion or conjugated enamine were investigated by enzymatic kinetics and UV-vis difference spectroscopy. Depending of the substituent R (methyl or aromatic ring), a competitive or a slow-binding inhibition takes place. These results were examined on the basis of the three-dimensional structure of the enzyme. PMID:15142555

  18. Acetylene is an active-site-directed, slow-binding, reversible inhibitor of Azotobacter vinelandii hydrogenase

    International Nuclear Information System (INIS)

    The inhibition of purified and membrane-bound hydrogenase from Azotobacter vinelandii by dihydrogen-free acetylene was investigated. The inhibition was a time-dependent process which exhibited first-order kinetics. Both H2 and CO protected against the inhibition by acetylene. K/sub protect(app)/ values of 0.41 and 24 μM were derived for these gases, respectively. Both H2-oxidizing activity and the tritium exchange capacity of the purified enzyme were inhibited at the same rate by acetylene. Removal of acetylene reversed the inhibition for both the purified and the membrane-associated form of the enzyme. The purified hydrogenases from both Rhizobium japonicum and Alcaligenes eutrophus H16 were also inhibited by acetylene in a time-dependent fashion. These findings suggest that acetylene is an active-site-directed, slow-binding, reversible inhibitor of some membrane-bound hydrogenases from aerobic bacteria

  19. Plasma protein S contains zinc essential for efficient activated protein C-independent anticoagulant activity and binding to factor Xa, but not for efficient binding to tissue factor pathway inhibitor

    OpenAIRE

    Heeb, Mary J.; Prashun, Duane; Griffin, John H; Bouma, Bonno N.

    2009-01-01

    Protein S (PS) is a cofactor for activated protein C (APC), which inactivates coagulation factors (F) Va and VIIIa. Deficiency of protein C or PS is associated with risk of thrombosis. We found that PS also has APC-independent anticoagulant activity (PS-direct) and directly inhibits thrombin generated by FXa/FVa (prothrombinase complex). Here we report that PS contains Zn2+ that is required for PS-direct and that is lost during certain purification procedures. Immunoaffinity-purified PS conta...

  20. Sodium Channels: Ionic Model of Slow Inactivation and State-Dependent Drug Binding

    OpenAIRE

    Tikhonov, Denis B.; Zhorov, Boris S.

    2007-01-01

    Inactivation is a fundamental property of voltage-gated ion channels. Fast inactivation of Na+ channels involves channel block by the III–IV cytoplasmic interdomain linker. The mechanisms of nonfast types of inactivation (intermediate, slow, and ultraslow) are unclear, although the ionic environment and P-loops rearrangement appear to be involved. In this study, we employed a TTX-based P-loop domain model of a sodium channel and the MCM method to investigate a possible role of P-loop rearrang...

  1. Pyridoxal 5'-phosphate is a slow tight binding inhibitor of E. coli pyridoxal kinase.

    Directory of Open Access Journals (Sweden)

    Mohini S Ghatge

    Full Text Available Pyridoxal 5'-phosphate (PLP is a cofactor for dozens of B(6 requiring enzymes. PLP reacts with apo-B(6 enzymes by forming an aldimine linkage with the ε-amino group of an active site lysine residue, thus yielding the catalytically active holo-B(6 enzyme. During protein turnover, the PLP is salvaged by first converting it to pyridoxal by a phosphatase and then back to PLP by pyridoxal kinase. Nonetheless, PLP poses a potential toxicity problem for the cell since its reactive 4'-aldehyde moiety forms covalent adducts with other compounds and non-B(6 proteins containing thiol or amino groups. The regulation of PLP homeostasis in the cell is thus an important, yet unresolved issue. In this report, using site-directed mutagenesis, kinetic, spectroscopic and chromatographic studies we show that pyridoxal kinase from E. coli forms a complex with the product PLP to form an inactive enzyme complex. Evidence is presented that, in the inhibited complex, PLP has formed an aldimine bond with an active site lysine residue during catalytic turnover. The rate of dissociation of PLP from the complex is very slow, being only partially released after a 2-hour incubation with PLP phosphatase. Interestingly, the inactive pyridoxal kinase•PLP complex can be partially reactivated by transferring the tightly bound PLP to an apo-B(6 enzyme. These results open new perspectives on the mechanism of regulation and role of pyridoxal kinase in the Escherichia coli cell.

  2. A selective, slow binding inhibitor of factor VIIa binds to a nonstandard active site conformation and attenuates thrombus formation in vivo.

    Science.gov (United States)

    Olivero, Alan G; Eigenbrot, Charles; Goldsmith, Richard; Robarge, Kirk; Artis, Dean R; Flygare, John; Rawson, Thomas; Sutherlin, Daniel P; Kadkhodayan, Saloumeh; Beresini, Maureen; Elliott, Linda O; DeGuzman, Geralyn G; Banner, David W; Ultsch, Mark; Marzec, Ulla; Hanson, Stephen R; Refino, Canio; Bunting, Stuart; Kirchhofer, Daniel

    2005-03-11

    The serine protease factor VIIa (FVIIa) in complex with its cellular cofactor tissue factor (TF) initiates the blood coagulation reactions. TF.FVIIa is also implicated in thrombosis-related disorders and constitutes an appealing therapeutic target for treatment of cardiovascular diseases. To this end, we generated the FVIIa active site inhibitor G17905, which displayed great potency toward TF.FVIIa (Ki = 0.35 +/- 0.11 nM). G17905 did not appreciably inhibit 12 of the 14 examined trypsin-like serine proteases, consistent with its TF.FVIIa-specific activity in clotting assays. The crystal structure of the FVIIa.G17905 complex provides insight into the molecular basis of the high selectivity. It shows that, compared with other serine proteases, FVIIa is uniquely equipped to accommodate conformational disturbances in the Gln217-Gly219 region caused by the ortho-hydroxy group of the inhibitor's aminobenzamidine moiety located in the S1 recognition pocket. Moreover, the structure revealed a novel, nonstandard conformation of FVIIa active site in the region of the oxyanion hole, a "flipped" Lys192-Gly193 peptide bond. Macromolecular substrate activation assays demonstrated that G17905 is a noncompetitive, slow-binding inhibitor. Nevertheless, G17905 effectively inhibited thrombus formation in a baboon arterio-venous shunt model, reducing platelet and fibrin deposition by approximately 70% at 0.4 mg/kg + 0.1 mg/kg/min infusion. Therefore, the in vitro potency of G17905, characterized by slow binding kinetics, correlated with efficacious antithrombotic activity in vivo. PMID:15632123

  3. Radioimmunoassay of protein C system

    International Nuclear Information System (INIS)

    Protein C system is an anticoagulation pathway which consists of protein C (PC), protein S (PS), thrombomodulator (TM) and protein C inhibitor (PCI). Using the McAb SZ-57, the authors have established SZ-57-Sepharose CL-6B affinity chromatography to purify human urinary TM. A procedure for isolation and purification of PC, PS and PCI from albumin-free human plasma by rivanol precipitation was also established. The isolation steps include adsorption onto and elution from barium, PEG precipitation, ion-exchange chromatography and preparative isoelectric focusing and so on. The molecular weight, isoelectric points, amino acid contents and the functional activity of these proteins were consistent with other previous reports. Four radioimmunoassays (RIAs) of PC, PS, TM and PCI were established using the equilibrium method. 125I-PC and 125I-PS were prepared using the chloramine-T method. 125I-PCI was prepared by iodogen method and 125I-TM by Bolton-Hunter method. Their sensitivities were 3.94 μg/L, 9.87 μg/L, 6.16 μg/L and 2.58 μg/L, respectively. The recovery rates were 104.28%, 94.30%, 105.22% and 101.89. Some antiserum provided a linear response from 6.25 to 1024 μg/L for PC, 21 to 700 μg/L for PS, 8.1 to 560 μg/L for TM and 4.8 to 1024 μg/L for PCI. The intra- and inter-assay CV were 4.4% and 9.68% for PC RIA, respectively, 4.99% and 13.14% for PS RIA, 5.10% and 10.94% for TM RIA, 2.73% and 8.62% for PCI RIA. The cross reactivity with factor II, thrombin, and antithrombin III was negligible. These methods can be used as effective tools especially for diagnosis of thrombosis and basic or clinical studies of protein C system. (20 refs., 8 figs., 6 tabs.)

  4. ASP4000, a slow-binding dipeptidyl peptidase 4 inhibitor, has antihyperglycemic activity of long duration in Zucker fatty rats.

    Science.gov (United States)

    Tanaka-Amino, Keiko; Matsumoto, Kazumi; Hatakeyama, Yoshifumi; Takakura, Shoji; Mutoh, Seitaro

    2010-03-01

    ASP4000 ((2S)-1-{[(1R,3S,4S,6R)-6-hydroxy-2-azabicyclo[2.2.1]hept-3-yl]carbonyl}-2-pyrrolidinecarbonitrile hydrochloride) is a novel, potent and selective dipeptidyl peptidase 4 (DPP IV, EC 3.4.14.5) inhibitor (Keiko Tanaka-Amino et al. in Eur J pharmacol 59:444-449, 2008). The aim of the present study was to characterize the kinetic profile of and identify the long duration effect of the antihyperglycemic activity of ASP4000. ASP4000 was found to inhibit human recombinant DPP4 activity with a K(i) of 1.05 nM, a k(on) value of 22.3 x 10(5) M(-1) s(-1), and a k (off) of 2.35 x 10(-3) M(-1) s(-1), with higher affinity than that of vildagliptin. The kinetic studies indicate that both the formation and dissociation of ASP4000/DPP4 complex were faster than those of vildagliptin, and that ASP4000 slow-bindingly inhibits DPP4 with a different mode of inhibition than vildagliptin. In addition, ASP4000 augmented the insulin response and ameliorated the glucose excursion during the oral glucose tolerance test in Zucker fatty rats at 4 h post dosing. ASP4000 is expected to be a promising, long duration DPP4 inhibitor for type 2 diabetes. PMID:19238312

  5. IgG antibodies to endothelial protein C receptor-binding Cysteine-rich interdomain region domains of Plasmodium falciparum erythrocyte membrane protein 1 are acquired early in life in individuals exposed to malaria

    DEFF Research Database (Denmark)

    Turner, Louise; Lavstsen, Thomas; Mmbando, Bruno P;

    2015-01-01

    Severe malaria syndromes are precipitated by Plasmodium falciparum parasites binding to endothelial receptors on the vascular lining. This binding is mediated by members of the highly variant P. falciparum erythrocyte membrane protein 1 (PfEMP1) family. We have previously identified a subset of Pf...

  6. Weak glycolipid binding of a microdomain-tracer peptide correlates with aggregation and slow diffusion on cell membranes.

    Directory of Open Access Journals (Sweden)

    Tim Lauterbach

    Full Text Available Organized assembly or aggregation of sphingolipid-binding ligands, such as certain toxins and pathogens, has been suggested to increase binding affinity of the ligand to the cell membrane and cause membrane reorganization or distortion. Here we show that the diffusion behavior of the fluorescently tagged sphingolipid-interacting peptide probe SBD (Sphingolipid Binding Domain is altered by modifications in the construction of the peptide sequence that both result in a reduction in binding to ganglioside-containing supported lipid membranes, and at the same time increase aggregation on the cell plasma membrane, but that do not change relative amounts of secondary structural features. We tested the effects of modifying the overall charge and construction of the SBD probe on its binding and diffusion behavior, by Surface Plasmon Resonance (SPR; Biacore analysis on lipid surfaces, and by Fluorescence Correlation Spectroscopy (FCS on live cells, respectively. SBD binds preferentially to membranes containing the highly sialylated gangliosides GT1b and GD1a. However, simple charge interactions of the peptide with the negative ganglioside do not appear to be a critical determinant of binding. Rather, an aggregation-suppressing amino acid composition and linker between the fluorophore and the peptide are required for optimum binding of the SBD to ganglioside-containing supported lipid bilayer surfaces, as well as for interaction with the membrane. Interestingly, the strength of interactions with ganglioside-containing artificial membranes is mirrored in the diffusion behavior by FCS on cell membranes, with stronger binders displaying similar characteristic diffusion profiles. Our findings indicate that for aggregation-prone peptides, aggregation occurs upon contact with the cell membrane, and rather than giving a stronger interaction with the membrane, aggregation is accompanied by weaker binding and complex diffusion profiles indicative of heterogeneous

  7. 补体蛋白C3c与抑制剂Compstatin的结合自由能计算%Binding free energy calculation of complement protein C3c-inhibitor Compstatin interaction by MM/PBSA method

    Institute of Scientific and Technical Information of China (English)

    杨威; 张峰; 马志; 郑俊峰

    2013-01-01

    The binding free energy of human C3c-Compstatin complex was calculated by an MM/PBS A method, and the key residues interactions were also investigated between MG4-MG5 binding domain of C3c and Compstatin by using energy decomposition method. The results showed that the calculated binding free energy ( - 8. 06 kcal/mol) was in high agreement with the binding affinity(-6.72 kcal/mol)- by the experimental essays, the total energy in the molecule( -177.24 kcal/mol) showing the maximal contribution to binding complement inhibitor, followed by vaccum electrostatic interaction(-108.74 kcal/mol)and Vander Waals interaction(-68.51 kcal/mol). The dynamic process of combination between C3c and the inhibitor together with the changes of the protein under the effect of combination was simulated as a complementary part in the crystal experiments. Our molecular dynamics stimulation proved the experiment with the structure information: Residue ARG459, ASP491, MET457 of C3c and TRP7,TRP4,HIS10 of Compstatin had major contribution to the binding free energy of the complex. The information above provides some insights into the based structural design of inhibitor of complement 3.%采用分子动力学模拟取样,运用MM-PBSA方法计算了人类C3c-Compstatin复合物的结合自由能.通过能量分解方法探究了人类补体蛋白C3c上抑制剂结合域MG4~MG5(巨球蛋白区域)上的主要残基与配体Compstatin纤维蛋白之间的相互作用和识别.结果表明:C3c与补体抑制剂Compstatin的理论结合自由能(-8.06 kcal/mol)与试验值(-6.72 kcal/mol)吻合较好,分子内能总和(-177.24 kcal/mol)对补体抵制剂的结合贡献最大,其次为真空静电作用能(-108.74 kcal/mol)和范德华作用能(-68.51kcal/mol).作为对结晶试验的补充,进行了C3c蛋白和小分子抑制剂之间结合的动态过程以及在两者结合的影响下蛋白形态变化的分子动力学模拟,结果发现C3c上的残基ARG459、ASP491、MET457

  8. Characterization of the slow calcium channel binding sites for [3H]SR 33557 in rat heart sarcolemmal membranes

    International Nuclear Information System (INIS)

    SR 33557 represents a new class of compounds (indolizine sulfone) that inhibit L-type Ca2+ channels. [3H]SR 33557 has been shown to bind with high affinity (Kd congruent to 0.36 nM, calculated from saturation isotherms and association/dissociation kinetics) to a single class of sites in a purified preparation of rat cardiac sarcolemmal membranes. The binding was found to be saturable and reversible. The maximal binding capacity was in approximately 1:1 stoichiometry with that of other Ca2+ channel antagonists. Various divalent cations (Mg2+, Mn2+, Ca2+, Ba2+, and Cd2+) were shown to inhibit specific [3H]SR 33557 binding, with Cd2+ being the most potent. Among several receptor or channel ligands (including omega-conotoxin and Na+ and K+ channel modulators), only the L-type Ca2+ channel antagonists were found to displace [3H]SR 33557. However, dihydropyridines, phenylalkylamines, benzothiazepines, and diphenylbutylpiperidines were found to inhibit [3H]SR 33557 in a noncompetitive manner as demonstrated by displacement and saturation experiments in addition to dissociation kinetics. From these results, we suggest that SR 33557 binds with high affinity to a unique site on the L-type Ca2+ channel found in rat cardiac sarcolemmal membranes

  9. Slow-binding inhibition of acetylcholinesterase by an alkylammonium derivative of 6-methyluracil: mechanism and possible advantages for myasthenia gravis treatment.

    Science.gov (United States)

    Kharlamova, Alexandra D; Lushchekina, Sofya V; Petrov, Konstantin A; Kots, Ekaterina D; Nachon, Florian; Villard-Wandhammer, Marielle; Zueva, Irina V; Krejci, Eric; Reznik, Vladimir S; Zobov, Vladimir V; Nikolsky, Evgeny E; Masson, Patrick

    2016-05-01

    Inhibition of human AChE (acetylcholinesterase) and BChE (butyrylcholinesterase) by an alkylammonium derivative of 6-methyluracil, C-547, a potential drug for the treatment of MG (myasthenia gravis) was studied. Kinetic analysis of AChE inhibition showed that C-547 is a slow-binding inhibitor of type B, i.e. after formation of the initial enzyme·inhibitor complex (Ki=140 pM), an induced-fit step allows establishment of the final complex (Ki*=22 pM). The estimated koff is low, 0.05 min(-1) On the other hand, reversible inhibition of human BChE is a fast-binding process of mixed-type (Ki=1.77 μM; Ki'=3.17 μM). The crystal structure of mouse AChE complexed with C-547 was solved at 3.13 Å resolution. The complex is stabilized by cation-π, stacking and hydrogen-bonding interactions. Molecular dynamics simulations of the binding/dissociation processes of C-547 and C-35 (a non-charged analogue) to mouse and human AChEs were performed. Molecular modelling on mouse and human AChE showed that the slow step results from an enzyme conformational change that allows C-547 to cross the bottleneck in the active-site gorge, followed by formation of tight complex, as observed in the crystal structure. In contrast, the related non-charged compound C-35 is not a slow-binding inhibitor. It does not cross the bottleneck because it is not sensitive to the electrostatic driving force to reach the bottom of the gorge. Thus C-547 is one of the most potent and selective reversible inhibitors of AChE with a long residence time, τ=20 min, longer than for other reversible inhibitors used in the treatment of MG. This makes C-547 a promising drug for the treatment of this disease. PMID:26929400

  10. Molecular dynamics of surfactant protein C

    DEFF Research Database (Denmark)

    Ramírez, Eunice; Santana, Alberto; Cruz, Anthony;

    2006-01-01

    Surfactant protein C (SP-C) is a membrane-associated protein essential for normal respiration. It has been found that the alpha-helix form of SP-C can undergo, under certain conditions, a transformation from an alpha-helix to a beta-strand conformation that closely resembles amyloid fibrils, which...

  11. Erythromycin, roxithromycin, and clarithromycin: use of slow-binding kinetics to compare their in vitro interaction with a bacterial ribosomal complex active in peptide bond formation.

    Science.gov (United States)

    Dinos, George P; Connell, Sean R; Nierhaus, Knud H; Kalpaxis, Dimitrios L

    2003-03-01

    In a cell-free system derived from Escherichia coli, it is shown that clarithromycin and roxithromycin, like their parent compound erythromycin, do not inhibit the puromycin reaction (i.e., the peptide bond formation between puromycin and AcPhe-tRNA bound at the P-site of 70S ribosomes programmed with heteropolymeric mRNA). Nevertheless, all three antibiotics compete for binding on the ribosome with tylosin, a 16-membered ring macrolide that behaves as a slow-binding, slowly reversible inhibitor of peptidyltransferase. The mutually exclusive binding of these macrolides to ribosomes is also corroborated by the fact that they protect overlapping sites in domain V of 23S rRNA from chemical modification by dimethyl sulfate. From this competition effect, detailed kinetic analysis revealed that roxithromycin or clarithromycin (A), like erythromycin, reacts rapidly with AcPhe-tRNA.MF-mRNA x 70S ribosomal complex (C) to form the encounter complex CA which is then slowly isomerized to a more tight complex, termed C*A. The value of the overall dissociation constant, K, encompassing both steps of macrolide interaction with complex C, is 36 nM for erythromycin, 20 nM for roxithromycin, and 8 nM for clarithromycin. Because the off-rate constant of C*A complex does not significantly differ among the three macrolides, the superiority of clarithromycin as an inhibitor of translation in E. coli cells and many Gram-positive bacteria may be correlated with its greater rate of association with ribosomes. PMID:12606769

  12. Slow-binding and competitive inhibition of 8-amino-7-oxopelargonate synthase, a pyridoxal-5'-phosphate-dependent enzyme involved in biotin biosynthesis, by substrate and intermediate analogs. Kinetic and binding studies.

    Science.gov (United States)

    Ploux, O; Breyne, O; Carillon, S; Marquet, A

    1999-01-01

    8-Amino-7-oxopelargonate synthase catalyzes the first committed step of biotin biosynthesis in micro-organisms and plants. Because inhibitors of this pathway might lead to antibacterials or herbicides, we have undertaken an inhibition study on 8-amino-7-oxopelargonate synthase using six different compounds. d-Alanine, the enantiomer of the substrate of this pyridoxal-5'-phosphate-dependent enzyme was found to be a competitive inhibitor with respect to l-alanine with a Ki of 0.59 mm. The fact that this inhibition constant was four times lower than the Km for l-alanine was interpreted as the consequence of the inversion-retention stereochemistry of the catalyzed reaction. Schiff base formation between l or d-alanine and pyridoxal-5'-phosphate, in the active site of the enzyme, was studied using ultraviolet/visible spectroscopy. It was found that l and d-alanine form an external aldimine with equilibrium constants K = 4.1 mm and K = 37.8 mm, respectively. However, the equilibrium constant for d-alanine aldimine formation dramatically decreased to 1.3 mm in the presence of saturating concentration of pimeloyl-CoA, the second substrate. This result strongly suggests that the binding of pimeloyl-CoA induces a conformational change in the active site, and we propose that this new topology is complementary to d-alanine and to the putative reaction intermediate since they both have the same configuration. (+/-)-8-Amino-7-oxo-8-phosphonononaoic acid (1), the phosphonate derivative of the intermediate formed during the reaction, was our most potent inhibitor with a Ki of 7 microm. This compound behaved as a reversible slow-binding inhibitor, competitive with respect to l-alanine. Kinetic investigation showed that this slow process was best described by a one-step mechanism (mechanism A) with the following rate constants: k1 = 0.27 x 103 m-1.s-1, k2 = 1.8 s-1 and half-life for dissociation t1/2 = 6.3 min. The binding of compound 1 to the enzyme was also studied using

  13. The protein C omega-loop substitution Asn2Ile is associated with reduced protein C anticoagulant activity.

    LENUS (Irish Health Repository)

    Preston, Roger J S

    2012-02-01

    We report a kindred with heritable protein C (PC) deficiency in which two siblings with severe thrombosis showed a composite type I and IIb PC deficiency phenotype, identified using commercial PC assays (proband: PC antigen 42 u\\/dl, amidolytic activity 40 u\\/dl, anticoagulant activity 9 u\\/dl). The independent PROC nucleotide variations c.669C>A (predictive of Ser181Arg) and c.131C>T (predictive of Asn2Ile) segregated with the type I and type IIb PC deficiency phenotypes respectively, but co-segregated in the siblings with severe thrombosis. Soluble thrombomodulin (sTM)-mediated inhibition of plasma thrombin generation from an individual with PC-Asn2Ile was lower (endogenous thrombin potential (ETP) 56 +\\/- 1% that of ETP determined without sTM) than control plasma (ETP 15 +\\/- 2%) indicating reduced PC anticoagulant activity. Recombinant APC-Asn2Ile exhibited normal amidolytic activity but impaired anticoagulant activity. Protein S (PS)-dependent anticoagulant activity of recombinant APC-Asn2Ile and binding of recombinant APC-Asn2Ile to endothelial protein C receptor (EPCR) were reduced compared to recombinant wild-type APC. Asn2 lies within the omega-loop of the PC\\/APC Gla domain and this region is critical for calcium-induced folding and subsequent interactions with anionic phospholipids, EPCR and PS. The disruption of these interactions in this naturally-occurring PC variant highlights their collective importance in mediating APC anticoagulant activity in vivo.

  14. Use of human protein C concentrates in the treatment of patients with severe congenital protein C deficiency

    Directory of Open Access Journals (Sweden)

    Sabine Kroiss

    2010-03-01

    Full Text Available Sabine Kroiss, Manuela AlbisettiDivision of Hematology, University Children’s Hospital, Zurich, SwitzerlandAbstract: Protein C is one of the major inhibitors of the coagulation system that downregulate thrombin generation. Severe congenital protein C deficiency leads to a hypercoagulability state that usually presents at birth with purpura fulminans and/or severe venous and arterial thrombosis. Recurrent thrombotic events are commonly seen. From the 1990’s, several virus-inactivated human protein C concentrates have been developed. These concentrates currently constitute the therapy of choice for the treatment and prevention of clinical manifestations of severe congenital protein C deficiency. This review summarizes the available information on the use of human protein C concentrates in patients with severe congenital protein C deficiency.Keywords: Congenital protein C deficiency, protein C concentrate, purpura fulminans

  15. Protein C activators in snake venoms.

    Science.gov (United States)

    Stocker, K; Fischer, H; Meier, J; Brogli, M; Svendsen, L

    1986-02-01

    Venoms of 32 snake species were tested for protein C (PC) activating potency. As measured with the chromogenic PC substrate D-Pro-L-Pro-L-Arg-pNA, eleven venoms were able to generate amidolytic activity from purified bovine PC. In five venom solutions (Bothrops moojeni, B. pradoi, Cerastes cerastes, Vipera lebetina and V. russellii) the PC activating potency was destroyed during 10 min heating at 70 degrees C at pH 3, whereas in six venom solutions (Agkistrodon contortrix contortrix, A. c. mokasen, A. c. pictigaster, Agkistrodon piscivorus, A. p. leucostoma and A. bilineatus) the PC activator was stable under these conditions. PC activator from A. c. contortrix (Protac) was purified to homogeneity and characterized as a single chain polypeptide with a molecular weight of approx. 39-42,000 Dalton. Protac does not exert proteinase activity and is not inhibited by proteinase inhibitors; PC activation with Protac seems to be a stoichiometric reaction. The use of Protac in quantitative PC determination bears significant advantages over the use of thrombin as an activator. In rabbits, i.v. injection of Protac caused a prolonged APTT and did not provoke acute toxic reactions. PMID:3755037

  16. Erythrocyte-derived microparticles supporting activated protein C-mediated regulation of blood coagulation.

    Directory of Open Access Journals (Sweden)

    Ruzica Livaja Koshiar

    Full Text Available Elevated levels of erythrocyte-derived microparticles are present in the circulation in medical conditions affecting the red blood cells. Erythrocyte-derived microparticles expose phosphatidylserine thus providing a suitable surface for procoagulant reactions leading to thrombin formation via the tenase and prothrombinase complexes. Patients with elevated levels of circulating erythrocyte-derived microparticles have increased thrombin generation in vivo. The aim of the present study was to investigate whether erythrocyte-derived microparticles are able to support the anticoagulant reactions of the protein C system. Erythrocyte-derived microparticles were isolated using ultracentrifugation after incubation of freshly prepared erythrocytes with the ionophore A23187 or from outdated erythrocyte concentrates, the different microparticles preparations yielding similar results. According to flow cytometry analysis, the microparticles exposed phoshatidylserine and bound lactadherin, annexin V, and protein S, which is a cofactor to activated protein C. The microparticles were able to assemble the tenase and prothrombinase complexes and to stimulate the formation of thrombin in plasma-based thrombin generation assay both in presence and absence of added tissue factor. The addition of activated protein C in the thrombin generation assay inhibited thrombin generation in a dose-dependent fashion. The anticoagulant effect of activated protein C in the thrombin generation assay was inhibited by a monoclonal antibody that prevents binding of protein S to microparticles and also attenuated by anti-TFPI antibodies. In the presence of erythrocyte-derived microparticles, activated protein C inhibited tenase and prothrombinase by degrading the cofactors FVIIIa and FVa, respectively. Protein S stimulated the Arg306-cleavage in FVa, whereas efficient inhibition of FVIIIa depended on the synergistic cofactor activity of protein S and FV. In summary, the erythrocyte

  17. EDITORIAL: Slow light Slow light

    Science.gov (United States)

    Boyd, Robert; Hess, Ortwin; Denz, Cornelia; Paspalakis, Emmanuel

    2010-10-01

    Research into slow light began theoretically in 1880 with the paper [1] of H A Lorentz, who is best known for his work on relativity and the speed of light. Experimental work started some 60 years later with the work of S L McCall and E L Hahn [2] who explored non-linear self-induced transparency in ruby. This field of research has burgeoned in the last 10 years, starting with the work of L Vestergaard Hau and coworkers on slow light via electromagnetically induced transparency in a Bose-Einstein condensate [3]. Many groups are now able to slow light down to a few metres per second or even stop the motion of light entirely [4]. Today, slow light - or more often `slow and fast light' - has become its own vibrant field with a strongly increasing number of publications. In broad scope, slow light research can be categorized in terms of the sort of physical mechanism used to slow down the light. One sort of slow light makes use of material dispersion. This dispersion can be the natural dispersion of the ordinary refractive index or can be the frequency dependence of some nonlinear optical process, such as electromagnetically induced transparency, coherent population oscillations, stimulated light scattering, or four-wave mixing processes. The second sort of slow light makes use of the wavelength dependence of artificially structured materials, such as photonic crystals, optical waveguides, and collections of microresonators. Material systems in which slow light has been observed include metal vapours, rare-earth-doped materials, Raman and Brillioun gain media, photonic crystals, microresonators and, more recently, metamaterials. A common feature of all of these schemes is the presence of a sharp single resonance or multiple resonances produced by an atomic transition, a resonance in a photonic structure, or in a nonlinear optical process. Current applications of slow light include a series of attractive topics in optical information processing, such as optical data

  18. Potent inhibitors of HIV-1 integrase display a two-step, slow-binding inhibition mechanism which is absent in a drug-resistant T66I/M154I mutant.

    Science.gov (United States)

    Garvey, Edward P; Schwartz, Benjamin; Gartland, Margaret J; Lang, Scott; Halsey, Wendy; Sathe, Ganesh; Carter, H Luke; Weaver, Kurt L

    2009-02-24

    Two-metal binding HIV-1 integrase inhibitors (INIs) are potent inhibitors of HIV-1 in vitro and in patients. We report here for the first time the kinetics of inhibition of integrase-catalyzed strand transfer. First, the IC(50) values for each of six structurally distinct INIs decreased when a preincubation was included: S-1360 (1.3 microM vs 0.12 microM), L-731,988 (130 nM vs 9 nM), L-870,810 (130 nM vs 4 nM), raltegravir (300 nM vs 9 nM), elvitegravir (90 nM vs 6 nM), and GSK364735 (90 nM vs 6 nM). When reactions with these INIs were initiated with integrase, progress curve analyses indicated time-dependent inhibition, which could be fitted to a two-step mechanism of binding. Overall fitted K(i) values matched the IC(50) values measured with a preincubation: S-1360 (0.17 microM), L-731,988 (34 nM), L-870,810 (2.4 nM), raltegravir (10 nM), elvitegravir (4.0 nM), and GSK364735 (2.5 nM). To begin to understand the mechanism for this slow onset of inhibition and its possible impact on drug resistance, studies of resistance mutations were initiated. T66I/M154I exhibited little if any time-dependent inhibition by any of the six INIs, as measured by differences in potency upon preincubation or by progress curve analysis. These data demonstrate that slow binding is a signature of two-metal binding INIs, and that the second slow step is required for full potency. We discuss a possible structural explanation of the second slow step of inhibition and also the relationship between loss of time-dependent inhibition and drug resistance of this important new class of HIV-1 antiretroviral drugs. PMID:19178153

  19. Bilateral leukocoria in a patient with homozygous protein C deficiency

    International Nuclear Information System (INIS)

    We describe a bilateral leukocoria and neonatal purpura fulminans in a male infant, born at full term after an unremarkable pregnancy to a healthy consanguineous married couple. Multiple hemorrhagic skin bullae were found at birth on various parts of the body with bilateral leukocoria, organized vitreous hemorrhage, retinal detachment, and intracranial hemorrhage with undetectable levels of protein C activity. We report a clinical case of homozygous protein-C deficiency with severe purpura fulminans and bilateral leukocoria. (author)

  20. Activated protein C modulates the proinflammatory activity of dendritic cells

    Directory of Open Access Journals (Sweden)

    Matsumoto T

    2015-05-01

    Full Text Available Takahiro Matsumoto,1,2* Yuki Matsushima,1* Masaaki Toda,1 Ziaurahman Roeen,1 Corina N D'Alessandro-Gabazza,1,5 Josephine A Hinneh,1 Etsuko Harada,1,3 Taro Yasuma,4 Yutaka Yano,4 Masahito Urawa,1,5 Tetsu Kobayashi,5 Osamu Taguchi,5 Esteban C Gabazza1 1Department of Immunology, Mie University Graduate School of Medicine, Tsu, Mie Prefecture, 2BONAC Corporation, BIO Factory 4F, Fukuoka, 3Iwade Research Institute of Mycology, 4Department of Endocrinology, Diabetes and Metabolism, 5Department of Pulmonary and Critical Care Medicine, Mie University Graduate School of Medicine, Tsu, Mie Prefecture, Japan *These authors contributed equally to this work Background: Previous studies have demonstrated the beneficial activity of activated protein C in allergic diseases including bronchial asthma and rhinitis. However, the exact mechanism of action of activated protein C in allergies is unclear. In this study, we hypothesized that pharmacological doses of activated protein C can modulate allergic inflammation by inhibiting dendritic cells. Materials and methods: Dendritic cells were prepared using murine bone marrow progenitor cells and human peripheral monocytes. Bronchial asthma was induced in mice that received intratracheal instillation of ovalbumin-pulsed dendritic cells. Results: Activated protein C significantly increased the differentiation of tolerogenic plasmacytoid dendritic cells and the secretion of type I interferons, but it significantly reduced lipopolysaccharide-mediated maturation and the secretion of inflammatory cytokines in myeloid dendritic cells. Activated protein C also inhibited maturation and the secretion of inflammatory cytokines in monocyte-derived dendritic cells. Activated protein C-treated dendritic cells were less effective when differentiating naïve CD4 T-cells from Th1 or Th2 cells, and the cellular effect of activated protein C was mediated by its receptors. Mice that received adoptive transfer of activated protein C

  1. Further insight into the roles of the glycans attached to human blood protein C inhibitor

    DEFF Research Database (Denmark)

    Sun, Wei; Parry, Simon; Ubhayasekera, Wimal;

    2010-01-01

    . Furthermore, we have provided experimental evidence that PCI in both individuals is O-glycosylated on Thr20 with a core type 1 O-glycan, which is mostly NeuAcGalGalNAc. Modeling suggested that the O-glycan attachment site is located in proximity to several ligand-binding sites of the inhibitor.......Protein C inhibitor (PCI) is a 57-kDa glycoprotein that exists in many tissues and secretions in human. As a member of the serpin superfamily of proteins it displays unusually broad protease specificity. PCI is implicated in the regulation of a wide range of processes, including blood coagulation...

  2. FUNCTION OF THE ACTIVATED PROTEIN C (APC) AUTOLYSIS LOOP IN ACTIVATED FVIII INACTIVATION

    OpenAIRE

    Cramer, Thomas J.; Gale, Andrew J.

    2011-01-01

    Activated protein C (APC) binds to its substrates activated factor V (FVa) and activated factor VIII (FVIIIa) with a basic exosite that consists of loops 37, 60, 70 and the autolysis loop. These loops have a high density of basic residues, resulting in a positive charge on the surface of APC. Many of these residues are important in the interaction of APC with FVa and FVIIIa. The current study focused on the function of the autolysis loop in the interaction with FVIIIa. This loop was previousl...

  3. Platelet factor 4 impairs the anticoagulant activity of activated protein C.

    LENUS (Irish Health Repository)

    Preston, Roger J S

    2012-02-01

    Platelet factor 4 (PF4) is an abundant platelet alpha-granule chemokine released following platelet activation. PF4 interacts with thrombomodulin and the gamma-carboxyglutamic acid (Gla) domain of protein C, thereby enhancing activated protein C (APC) generation by the thrombin-thrombomodulin complex. However, the protein C Gla domain not only mediates protein C activation in vivo, but also plays a critical role in modulating the diverse functional properties of APC once generated. In this study we demonstrate that PF4 significantly inhibits APC anti-coagulant activity. PF4 inhibited both protein S-dependent APC anticoagulant function in plasma and protein S-dependent factor Va (FVa) proteolysis 3- to 5-fold, demonstrating that PF4 impairs protein S cofactor enhancement of APC anticoagulant function. Using recombinant factor Va variants FVa-R506Q\\/R679Q and FVa-R306Q\\/R679Q, PF4 was shown to impair APC proteolysis of FVa at position Arg(306) by 3-fold both in the presence and absence of protein S. These data suggest that PF4 contributes to the poorly understood APC resistance phenotype associated with activated platelets. Finally, despite PF4 binding to the APC Gla domain, we show that APC in the presence of PF4 retains its ability to initiate PAR-1-mediated cytoprotective signaling. In summary, we propose that PF4 acts as a critical regulator of APC generation, but also differentially targets APC toward cytoprotective, rather than anticoagulant function at sites of vascular injury with concurrent platelet activation.

  4. Platelet factor 4 impairs the anticoagulant activity of activated protein C.

    LENUS (Irish Health Repository)

    Preston, Roger J S

    2009-02-27

    Platelet factor 4 (PF4) is an abundant platelet alpha-granule chemokine released following platelet activation. PF4 interacts with thrombomodulin and the gamma-carboxyglutamic acid (Gla) domain of protein C, thereby enhancing activated protein C (APC) generation by the thrombin-thrombomodulin complex. However, the protein C Gla domain not only mediates protein C activation in vivo, but also plays a critical role in modulating the diverse functional properties of APC once generated. In this study we demonstrate that PF4 significantly inhibits APC anti-coagulant activity. PF4 inhibited both protein S-dependent APC anticoagulant function in plasma and protein S-dependent factor Va (FVa) proteolysis 3- to 5-fold, demonstrating that PF4 impairs protein S cofactor enhancement of APC anticoagulant function. Using recombinant factor Va variants FVa-R506Q\\/R679Q and FVa-R306Q\\/R679Q, PF4 was shown to impair APC proteolysis of FVa at position Arg(306) by 3-fold both in the presence and absence of protein S. These data suggest that PF4 contributes to the poorly understood APC resistance phenotype associated with activated platelets. Finally, despite PF4 binding to the APC Gla domain, we show that APC in the presence of PF4 retains its ability to initiate PAR-1-mediated cytoprotective signaling. In summary, we propose that PF4 acts as a critical regulator of APC generation, but also differentially targets APC toward cytoprotective, rather than anticoagulant function at sites of vascular injury with concurrent platelet activation.

  5. Purpura fulminans due to acquired protein C deficiency

    Directory of Open Access Journals (Sweden)

    Devdeep Mukherjee

    2015-01-01

    Full Text Available Purpura fulminans (PF may be the presenting symptom in a patient with protein C (PC deficiency. It is a hematological emergency and presents with extensive areas of hemorrhagic necrosis of the skin. PC deficiency is usually genetically inherited. However, we report a 1 year and 4 months boy, who presented with acquired PC deficiency possibly of postinfectious etiology and developed PF.

  6. Cell painting with an engineered EPCR to augment the protein C system.

    Science.gov (United States)

    Bouwens, Eveline A M; Stavenuiter, Fabian; Mosnier, Laurent O

    2015-11-25

    The protein C (PC) system conveys beneficial anticoagulant and cytoprotective effects in numerous in vivo disease models. The endothelial protein C receptor (EPCR) plays a central role in these pathways as cofactor for PC activation and by enhancing activated protein C (APC)-mediated protease-activated receptor (PAR) activation. During inflammatory disease, expression of EPCR on cell membranes is often diminished thereby limiting PC activation and APC's effects on cells. Here a caveolae-targeting glycosylphosphatidylinositol (GPI)-anchored EPCR (EPCR-GPI) was engineered to restore EPCR's bioavailability via "cell painting." The painting efficiency of EPCR-GPI on EPCR-depleted endothelial cells was time- and dose-dependent. The EPCR-GPI bioavailability after painting was long lasting since EPCR surface levels reached 400 % of wild-type cells after 2 hours and remained > 200 % for 24 hours. EPCR-GPI painting conveyed APC binding to EPCR-depleted endothelial cells where EPCR was lost due to shedding or shRNA. EPCR painting normalised PC activation on EPCR-depleted cells indicating that EPCR-GPI is functional active on painted cells. Caveolin-1 lipid rafts were enriched in EPCR after painting due to the GPI-anchor targeting caveolae. Accordingly, EPCR painting supported PAR1 and PAR3 cleavage by APC and augmented PAR1-dependent Akt phosphorylation by APC. Thus, EPCR-GPI painting achieved physiological relevant surface levels on endothelial cells, restored APC binding to EPCR-depleted cells, supported PC activation, and enhanced APC-mediated PAR cleavage and cytoprotective signalling. Therefore, EPCR-GPI provides a novel tool to restore the bioavailability and functionality of EPCR on EPCR- depleted and -deficient cells. PMID:26272345

  7. Substitution of glutamine for lysine at the pyridoxal phosphate binding site of bacterial D-amino acid transaminase. Effects of exogenous amines on the slow formation of intermediates.

    Science.gov (United States)

    Futaki, S; Ueno, H; Martinez del Pozo, A; Pospischil, M A; Manning, J M; Ringe, D; Stoddard, B; Tanizawa, K; Yoshimura, T; Soda, K

    1990-12-25

    In bacterial D-amino acid transaminase, Lys-145, which binds the coenzyme pyridoxal 5'-phosphate in Schiff base linkage, was changed to Gln-145 by site-directed mutagenesis (K145Q). The mutant enzyme had 0.015% the activity of the wild-type enzyme and was capable of forming a Schiff base with D-alanine; this external aldimine was formed over a period of minutes depending upon the D-alanine concentration. The transformation of the pyridoxal-5'-phosphate form of the enzyme to the pyridoxamine-5'-phosphate form (i.e. the half-reaction of transamination) occurred over a period of hours with this mutant enzyme. Thus, information on these two steps in the reaction and on the factors that influence them can readily be obtained with this mutant enzyme. In contrast, these reactions with the wild-type enzyme occur at much faster rates and are not easily studied separately. The mutant enzyme shows distinct preference for D- over L-alanine as substrates but it does so about 50-fold less effectively than the wild-type enzyme. Thus, Lys-145 probably acts in concert with the coenzyme and other functional side chain(s) to lead to efficient and stereochemically precise transamination in the wild-type enzyme. The addition of exogenous amines, ethanolamine or methyl amine, increased the rate of external aldimine formation with D-alanine and the mutant enzyme but the subsequent transformation to the pyridoxamine-5'-phosphate form of the enzyme was unaffected by exogenous amines. The wild-type enzyme displayed a large negative trough in the circular dichroic spectrum at 420 nm, which was practically absent in the mutant enzyme. However, addition of D-alanine to the mutant enzyme generated this negative Cotton effect (due to formation of the external aldimine with D-alanine). This circular dichroism band gradually collapsed in parallel with the transformation to the pyridoxamine-5'-phosphate enzyme. Further studies on this mutant enzyme, which displays the characteristics of the wild

  8. Is treatment with hydroxychloroquine effective in surfactant protein C deficiency?

    Science.gov (United States)

    Rabach, Ingrid; Poli, Furio; Zennaro, Floriana; Germani, Claudio; Ventura, Alessandro; Barbi, Egidio

    2013-05-01

    We present the case of two twin brothers with surfactant protein C deficiency who were treated with hydroxychloroquine for three years, with apparent success. The exact physiopathology of this disease is not known and there is no specific treatment for it. There is merely news from a few previous descriptions in the literature about the use of hydroxychloroquine for surfactant protein C deficiency with satisfactory results. Two years after the treatment was withdrawn, the twins were evaluated once again: they presented no new infections, growth and general state were normal and chest CT showed a notable additional reduction in the interstitial pneumopathy. These data seem to cast some doubt on the efficacy of hydroxychloroquine, and they suggest that the clinical improvement was simply the natural evolution of the disease. PMID:23137777

  9. Fluorescently labeled pulmonary surfactant protein C in spread phospholipid monolayers.

    OpenAIRE

    Nag, K.; Perez-Gil, J.; Cruz, A; Keough, K M

    1996-01-01

    Pulmonary surfactant, a lipid-protein complex, secreted into the fluid lining of lungs prevents alveolar collapse at low lung volumes. Pulmonary surfactant protein C (SP-C), an acylated, hydrophobic, alpha-helical peptide, enhances the surface activity of pulmonary surfactant lipids. Fluorescein-labeled SP-C (F-SP-C) (3, 6, 12 wt%) in dipalmitoylphosphatidylcholine (DPPC), and DPPC:dipalmitoylphosphatidylglycerol (DPPG) [DPPC:DPPG 7:3 mol/mol] in spread monolayers was studied by epifluorescen...

  10. Association of protein C23 with rapidly labeled nucleolar RNA

    Energy Technology Data Exchange (ETDEWEB)

    Herrera, A.H.; Olson, M.O.

    1986-10-07

    The association of nucleolar phosphoprotein C23 with preribosomal ribonucleoprotein (RNP) particles was examined in Novikoff hepatoma nucleoli. RNA was labeled with (/sup 3/H)uridine for various times in cell suspensions, and RNP particles were extracted from isolated nucleoli and fractionated by sucrose gradient ultracentrifugation. The majority of protein C23 cosedimented with fractions containing rapidly labeled RNA (RL fraction). To determine whether there was a direct association of RNA with protein C23, the RL fraction was exposed to ultraviolet (UV) light (254 nm) for short periods of time. After 2 min of exposure there was a 50% decrease in C23 as measured by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analyses, with no significant further decrease at longer times. When UV-treated fractions were subjected to phenol/chloroform extractions, as much as 30% of the labeled RNA was found in the phenol (protein) layer, indicating that RNA became cross-linked to protein. Similarly, there was an increase in protein C23 extracted into the water layer after irradiation. By SDS-PAGE analyses the cross-linked species migrated more slowly than protein C23, appearing as a smear detected either by (/sup 3/H)uridine radioactivity or by anti-C23 antibody. With anti-C23 antibodies, up to 25% of the labeled RNA was precipitated from the RL fraction. Dot-blot hybridizations, using cloned rDNA fragments as probes, indicated that the RNA in the RL fraction and the immunoprecipitated RNA contained sequences from 18S and 28S ribosomal RNA.

  11. Association of protein C23 with rapidly labeled nucleolar RNA

    International Nuclear Information System (INIS)

    The association of nucleolar phosphoprotein C23 with preribosomal ribonucleoprotein (RNP) particles was examined in Novikoff hepatoma nucleoli. RNA was labeled with [3H]uridine for various times in cell suspensions, and RNP particles were extracted from isolated nucleoli and fractionated by sucrose gradient ultracentrifugation. The majority of protein C23 cosedimented with fractions containing rapidly labeled RNA (RL fraction). To determine whether there was a direct association of RNA with protein C23, the RL fraction was exposed to ultraviolet (UV) light (254 nm) for short periods of time. After 2 min of exposure there was a 50% decrease in C23 as measured by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analyses, with no significant further decrease at longer times. When UV-treated fractions were subjected to phenol/chloroform extractions, as much as 30% of the labeled RNA was found in the phenol (protein) layer, indicating that RNA became cross-linked to protein. Similarly, there was an increase in protein C23 extracted into the water layer after irradiation. By SDS-PAGE analyses the cross-linked species migrated more slowly than protein C23, appearing as a smear detected either by [3H]uridine radioactivity or by anti-C23 antibody. With anti-C23 antibodies, up to 25% of the labeled RNA was precipitated from the RL fraction. Dot-blot hybridizations, using cloned rDNA fragments as probes, indicated that the RNA in the RL fraction and the immunoprecipitated RNA contained sequences from 18S and 28S ribosomal RNA

  12. Evolution and organization of the human protein C gene

    International Nuclear Information System (INIS)

    The authors have isolated overlapping phage genomic clones covering an area of 21 kilobases that encodes the human protein C gene. The gene is at least 11.2 kilobases long and is made up of nine exons and eight introns. Two regions homologous to epidermal growth factor and transforming growth factor are encoded by amino acids 46-91 and 92-136 and are precisely delimited by introns, as is a similar sequence in the genes for coagulation factor IX and tissue plasminogen activator. When homologous amino acids of factor IX and protein C are aligned, the positions of all eight introns correspond precisely, suggesting that these genes are the product of a relatively recent gene duplication. Nevertheless, the two genes are sufficiently distantly related that no nucleic acid homology remains in the intronic regions and that the size of the introns varies dramatically between the two genes. The similarity of the genes for factor IX and protein C suggests that they may be the most closely related members of the serine protease gene family involved in coagulation and fibrinolysis

  13. FROM SLOW FOOD TO SLOW TOURISM

    Directory of Open Access Journals (Sweden)

    Bac Dorin Paul

    2014-12-01

    Full Text Available One of the effects of globalization is the faster pace of our lives. This rhythm can be noticed in all aspects of life: travel, work, shopping, etc. and it has serious negative effects. It has become common knowledge that stress and speed generate serious medical issues. Food and eating habits in the modern world have taken their toll on our health. However, some people took a stand and argued for a new kind of lifestyle. It all started in the field of gastronomy, where a new movement emerged – Slow Food, based on the ideas and philosophy of Carlo Petrini. Slow Food represents an important adversary to the concept of fast food, and is promoting local products, enjoyable meals and healthy food. The philosophy of the Slow Food movement developed in several directions: Cittaslow, slow travel and tourism, slow religion and slow money etc. The present paper will account the evolution of the concept and its development during the most recent years. We will present how the philosophy of slow food was applied in all the other fields it reached and some critical points of view. Also we will focus on the presence of the slow movement in Romania, although it is in a very early stage of development. The main objectives of the present paper are: to present the chronological and ideological evolution of the slow movement; to establish a clear separation of slow travel and slow tourism, as many mistake on for the other; to review the presence of the slow movement in Romania. Regarding the research methodology, information was gathered from relevant academic papers and books and also from interviews and discussions with local entrepreneurs. The research is mostly theoretical and empirical, as slow food and slow tourism are emerging research themes in academic circles.

  14. Dissociation of activated protein C functions by elimination of protein S cofactor enhancement.

    LENUS (Irish Health Repository)

    Harmon, Shona

    2008-11-07

    Activated protein C (APC) plays a critical anticoagulant role in vivo by inactivating procoagulant factor Va and factor VIIIa and thus down-regulating thrombin generation. In addition, APC bound to the endothelial cell protein C receptor can initiate protease-activated receptor-1 (PAR-1)-mediated cytoprotective signaling. Protein S constitutes a critical cofactor for the anticoagulant function of APC but is not known to be involved in regulating APC-mediated protective PAR-1 signaling. In this study we utilized a site-directed mutagenesis strategy to characterize a putative protein S binding region within the APC Gla domain. Three single amino acid substitutions within the APC Gla domain (D35T, D36A, and A39V) were found to mildly impair protein S-dependent anticoagulant activity (<2-fold) but retained entirely normal cytoprotective activity. However, a single amino acid substitution (L38D) ablated the ability of protein S to function as a cofactor for this APC variant. Consequently, in assays of protein S-dependent factor Va proteolysis using purified proteins or in the plasma milieu, APC-L38D variant exhibited minimal residual anticoagulant activity compared with wild type APC. Despite the location of Leu-38 in the Gla domain, APC-L38D interacted normally with endothelial cell protein C receptor and retained its ability to trigger PAR-1 mediated cytoprotective signaling in a manner indistinguishable from that of wild type APC. Consequently, elimination of protein S cofactor enhancement of APC anticoagulant function represents a novel and effective strategy by which to separate the anticoagulant and cytoprotective functions of APC for potential therapeutic gain.

  15. Pharmacokinetics of activated protein C in guinea pigs

    International Nuclear Information System (INIS)

    Protein C is a vitamin K-dependent zymogen of the serine protease, activated protein C (APC), an important regulatory enzyme in hemostasis. In view of the potential of human APC as an anticoagulant and profibrinolytic agent, the pharmacokinetics and tissue distribution of APC were studied in guinea pigs. The plasma elimination of a trace dose of 125I-APC was biphasic following an initial rapid elimination of approximately 15% of the injected dose within 1 to 2 minutes. This rapid removal of 125I-APC from the circulation was found to be a result of an association with the liver regardless of the route of injection. Essentially identical results were obtained with active site-blocked forms of APC generated with either diisopropylfluorophosphate or D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone, which indicates that the active site was not essential for the liver association. Accumulation of all three forms of APC in the liver peaked at 30 minutes and then declined as increasing amounts of degraded radiolabeled material appeared in the gastrointestinal tract and urine. Removal of the gamma-carboxyglutamic acid (gla) domain of diisopropylphosphoryl-APC resulted in a 50% reduction in the association with liver and an accumulation in the kidneys. Protein C and protein S were cleared from the circulation at rates approximately one-half and one-fourth, respectively, that of APC. Both in vitro and in vivo, APC was found to form complexes with protease inhibitors present in guinea pig plasma. Complex formation resulted in a more rapid disappearance of the enzymatic activity of APC than elimination of the protein moiety. These findings indicate two distinct mechanisms for the elimination of APC. One mechanism involves reaction with plasma protease inhibitors and subsequent elimination by specific hepatic receptors. (Abstract Truncated)

  16. Relationship between protein C antigen and anticoagulant activity during oral anticoagulation and in selected disease states.

    OpenAIRE

    Vigano D'Angelo, S; Comp, P C; Esmon, C T; D'Angelo, A.

    1986-01-01

    Protein C is a natural vitamin K-dependent plasma anticoagulant, deficiencies of which have been found in patients with recurrent thrombosis and warfarin-induced skin necrosis. To appreciate more fully the role of protein C in disease states and during oral anticoagulation, a new functional assay for protein C involving adsorption of plasma protein C on a Ca+2-dependent monoclonal antibody, elution, quantitative activation, and assessment of plasma anticoagulant activity, has been developed. ...

  17. Natural coagulation inhibitors and active protein c resistance in preeclampsia

    Directory of Open Access Journals (Sweden)

    Cengiz Demir

    2010-01-01

    Full Text Available INTRODUCTION: The etiology of preeclampsia is not fully established. A few studies have shown a relationship between natural coagulation inhibitors and preeclampsia. OBJECTIVES: The purpose of this study was to investigate the status of natural coagulation inhibitors and active protein C resistance (APC-R in preeclampsia. PATIENTS AND METHODS: We studied 70 women with preeclampsia recruited consecutively and 70 healthy pregnant and 70 nonpregnant women as controls. Plasma protein C (PC, free protein S (fPS, antithrombin III (ATIII and APC-R were evaluated. RESULTS: ATIII values were found to be significantly lower in preeclamptic patients than in the control groups (p< 0.001. Nevertheless, there was no significant difference between the healthy pregnant and nonpregnant women groups (p=0.141. The fPS values of the preeclamptic and healthy pregnant groups were lower than that of the nonpregnant group (p< 0.001, and the fPS value of the preeclamptic pregnant women was lower than that of healthy pregnant women (p<0.001. The PC value of the preeclamptic pregnant women was lower than that of the control groups (p< 0.001. The PC value of the healthy pregnant women was lower than that of the nonpregnant women (p< 0.001. The mean APC activity values were lower in the preeclamptic patients than that of the control groups (p< 0.001, p< 0.001. The APC-R positivity rates of the preeclamptic groups were higher than that of the control groups (p<0.001. CONCLUSIONS: This study demonstrated that ATIII, fPS, PC values and APC resistance were lower and APC-R positivity was higher in preeclamptic women than in normal pregnant and nonpregnant women.

  18. Protein C system defects inflicted by the malaria parasite protein PfEMP1 can be overcome by a soluble EPCR variant

    DEFF Research Database (Denmark)

    Petersen, Jens E V; Bouwens, Eveline A M; Tamayo, Ibai;

    2015-01-01

    The Endothelial Protein C receptor (EPCR) is essential for the anticoagulant and cytoprotective functions of the Protein C (PC) system. Selected variants of the malaria parasite protein, Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) associated with severe malaria, including cerebral...... malaria, specifically target EPCR on vascular endothelial cells. Here, we examine the cellular response to PfEMP1 engagement to elucidate its role in malaria pathogenesis. Binding of the CIDRα1.1 domain of PfEMP1 to EPCR obstructed activated PC (APC) binding to EPCR and induced a loss of cellular EPCR...... interfere with (A)PC binding to cellular EPCR. E86A-sEPCR used as a decoy to capture PfEMP1, permitted normal PC activation on endothelial cells, normal barrier protective effects of APC, and greatly reduced cytoadhesion of infected erythrocytes to brain endothelial cells. These data imply important...

  19. C4b-binding protein protects coagulation factor Va from inactivation by activated protein C

    NARCIS (Netherlands)

    van de Poel, RHL; Meijers, JCM; Rosing, J; Tans, G; Bouma, Bonno N.

    2000-01-01

    We investigated the effect of C4BP on APC-mediated inactivation of factor Va (FVa) in the absence and presence of protein S. FVa inactivation was biphasic (k(506) = 4.4 x 10(8) M-1 s(-1), k(306) = 2.7 x 10(7) M-1 s(-1)), and protein S accelerated Arg(306) cleavage approximately 10-fold. Preincubatio

  20. Slow electrons kill the ozone

    International Nuclear Information System (INIS)

    A new method and apparatus (Trochoidal electron monochromator) to study the interactions of electrons with atoms, molecules and clusters was developed. Two applications are briefly reported: a) the ozone destruction in the atmosphere is caused by different reasons, a new mechanism is proposed, that slow thermal electrons are self added to the ozone molecule (O3) with a high frequency, then O3 is destroyed ( O3 + e- → O- + O2); b) another application is the study of the binding energy of the football molecule C60. (nevyjel)

  1. Teaching slowing down theory

    International Nuclear Information System (INIS)

    Some of the difficulties and limitations encountered when teaching neutron slowing down theory to nuclear engineering students, are examined. Specific problems in teaching the kinetics of the slowing down of neutrons, the neutron balance equation, resonance escape probabilities, and the continuous slowing down theory, are considered and it is suggested that, as far as possible, use should be made, by analogy, of the work already done with the students in deriving diffusion theory and its one group equation. (U.K.)

  2. Isolation and characterization of a protein C activator from tropical moccasin venom.

    Science.gov (United States)

    Nakagaki, T; Kazim, A L; Kisiel, W

    1990-06-15

    A protease from the venom of the tropical moccasin (Agkistrodon bilineatus) that activates protein C was purified to homogeneity by ion-exchange and gel permeation chromatography. The purified protease is a glycoprotein, and exhibited a molecular weight of 35,000 and 38,000 in SDS-PAGE under non-reducing and reducing conditions, respectively. The purified protease readily activated human protein C and steady-state kinetic parameters indicated an apparent Km for human protein C of 1.7 microM and an apparent kcat of 0.02 sec-1. Calcium inhibited the activation of human protein C by the venom protease (Ki = 93 microM). Amino-terminal sequence analysis revealed that the tropical moccasin protein C activator was highly homologous to the protein C activator isolated from Southern copperhead venom. PMID:2385829

  3. Secretion of Human Protein C in Mouse Milk

    Directory of Open Access Journals (Sweden)

    Chae-Won Park

    2015-03-01

    Full Text Available To determine the production of recombinant human protein C (rec-hPC in milk, we created two homozygous mice lines for the goat β-casein/hPC transgene. Females and males of both lines (#10 and #11 displayed normal growth, fertility, and lactated normally. The copy number of the transgene was about fivefold higher in #10 line as compared to #11 line. mRNA expression of the transgene was only detected in the mammary glands of both lines. Furthermore, mRNA expression was fourfold higher on day 7 than on day 1 during lactation. Northern blot analysis of mRNA expression in the #10 line of transgenic (Tg mice indicated a strong expression of the transgene in the mammary glands after seven days of lactation. Comparison of rec-hPC protein level with that of mRNA in the mammary glands showed a very similar pattern. A 52-kDa band corresponding to the hPC protein was strongly detected in mammary glands of the #10 line during lactation. We also detected two bands of heavy chain and one weak band of light chain in the milk of the #10 and #11 lines. One single band at 52 kDa was detected from CHO cells transfected with hPC cDNA. hPC was mainly localized in the alveolar epithelial cell of the mammary glands. The protein is strongly expressed in the cytoplasm of the cultured mammary gland tissue. hPC protein produced in milk ranged from 2 to 28 ng/mL. These experiments indicated that rec-hPC can be produced at high levels in mice mammary glands.

  4. 14-3-3 protein C-terminal stretch occupies ligand binding groove and is displaced by phosphopeptide binding

    Czech Academy of Sciences Publication Activity Database

    Šilhán, Jan; Obšilová, Veronika; Večeř, J.; Herman, P.; Šulc, Miroslav; Teisinger, Jan; Obšil, Tomáš

    2004-01-01

    Roč. 279, č. 47 (2004), s. 49113-49119. ISSN 0021-9258 R&D Projects: GA ČR GA204/03/0714; GA AV ČR KJB5011308; GA MŠk LZ1K03020 Institutional research plan: CEZ:AV0Z5011922; CEZ:MSM 113100001 Keywords : 14-3-3 protein * FRET * molecular dynamics Subject RIV: BO - Biophysics Impact factor: 6.355, year: 2004

  5. 14-3-3 protein C-terminal stretch occupies ligand binding groove and is displaced by phosphodipeptide binding

    Czech Academy of Sciences Publication Activity Database

    Šilhán, Jan; Obšilová, Veronika; Večeř, J.; Heřman, P.; Šulc, Miroslav; Teisinger, Jan; Obšil, Tomáš

    2005-01-01

    Roč. 12, č. 1 (2005), s. 41-41. ISSN 1211-5894. [Discussions in Structural Molecular Biology /4./. 10.03.2005-12.03.2005, Nové Hrady] R&D Projects: GA AV ČR(CZ) KJB5011308; GA ČR(CZ) GA204/03/0714; GA ČR(CZ) GA309/02/1479; GA MŠk(CZ) LZ1K03020 Institutional research plan: CEZ:AV0Z5011922 Keywords : 14-3-3 * fluorescence * phosphopeptide Subject RIV: BO - Biophysics

  6. Interaction of protein C inhibitor with the type II transmembrane serine protease enteropeptidase.

    Directory of Open Access Journals (Sweden)

    Thomas A Prohaska

    Full Text Available The serine protease inhibitor protein C inhibitor (PCI is expressed in many human tissues and exhibits broad protease reactivity. PCI binds glycosaminoglycans and certain phospholipids, which modulate its inhibitory activity. Enteropeptidase (EP is a type II transmembrane serine protease mainly found on the brush border membrane of epithelial cells in the duodenum, where it activates trypsinogen to initiate the digestion of food proteins. Some active EP is also present in duodenal fluid and has been made responsible for causing pancreatitis in case of duodeno-pancreatic reflux. Together with its substrate trypsinogen, EP is furthermore present in the epidermis and in some cancer cells. In this report, we show that PCI inhibited EP with an apparent 2nd order rate constant of 4.48 × 10(4 M(-1 s(-1. Low molecular weight (LMWH and unfractionated heparin (UFH slightly reduced the inhibitory effect of PCI. The SI (stoichiometry of inhibition value for the inhibition of EP by PCI was 10.8 in the absence and 17.9 in the presence of UFH (10 U/ml. By inhibiting trypsin, chymotrypsin, and additionally EP, PCI might play a role in the protection of the pancreas from autodigestion. Furthermore the interaction of PCI with EP may influence the regulation of epithelial differentiation.

  7. On the reasons for bombarding uranium with slow neutrons

    International Nuclear Information System (INIS)

    Form the concepts of slow neutrons, the binding energy and the excitation energy of complex nuclei, and the activation energy in nuclear fission, the four reasons for bombarding uranium with slow neutrons are summed up. Not only the reasons for uranium fission are brought in light, but also the micromechanism is dealt with

  8. Utilising cardiopulmonary bypass for cancer surgery. Malignancy-induced protein C deficiency and thrombophilia.

    LENUS (Irish Health Repository)

    Marshall, C

    2012-02-03

    Cardiopulmonary bypass has evolved over the last 30 years. It is an important tool for the cardiac surgeon today and also has applications in non-cardiac operations such as surgery to extract tumours. Such patients undergoing surgery for cancer may be at an increased risk of a thromboembolic event post surgery, due to disturbances in the normal clotting pathway leading to hypercoagulability. One such disturbance is malignancy-induced Protein C deficiency. A deficiency of Protein C can cause hypercoagulabitity. Recent studies have examined cardiopulmonary bypass and inherited Protein C deficiency. However, surgery for cancer patients with a malignancy-induced Protein C deficiency involving cardiopulmonary bypass has not been reported. Surgery using CPB in these patients may result in increased morbidity and mortality. The objective of this article is to review the literature in order to discuss the occurrence, the aetiology and possible management of cancer patients with malignancy-induced Protein C deficiencies that require cardiopulmonary bypass for their surgery.

  9. Transformer Industry Productivity Slows.

    Science.gov (United States)

    Otto, Phyllis Flohr

    1981-01-01

    Annual productivity increases averaged 2.4 percent during 1963-79, slowing since 1972 to 1.5 percent; computer-assisted design and product standardization aided growth in output per employee-hour. (Author)

  10. Slow medical education.

    Science.gov (United States)

    Wear, Delese; Zarconi, Joseph; Kumagai, Arno; Cole-Kelly, Kathy

    2015-03-01

    Slow medical education borrows from other "slow" movements by offering a complementary orientation to medical education that emphasizes the value of slow and thoughtful reflection and interaction in medical education and clinical care. Such slow experiences, when systematically structured throughout the curriculum, offer ways for learners to engage in thoughtful reflection, dialogue, appreciation, and human understanding, with the hope that they will incorporate these practices throughout their lives as physicians. This Perspective offers several spaces in the medical curriculum where slowing down is possible: while reading and writing at various times in the curriculum and while providing clinical care, focusing particularly on conducting the physical exam and other dimensions of patient care. Time taken to slow down in these ways offers emerging physicians opportunities to more fully incorporate their experiences into a professional identity that embodies reflection, critical awareness, cultural humility, and empathy. The authors argue that these curricular spaces must be created in a very deliberate manner, even on busy ward services, throughout the education of physicians. PMID:25426738

  11. Cutaneous necrosis in pregnancy secondary to activated protein C resistance in hereditary angioedema.

    Science.gov (United States)

    Perkins, W; Downie, I; Keefe, M; Chisholm, M

    1995-04-01

    A 26-year-old woman with hereditary angineurotic oedema (HAE) presented at 22 weeks gestation with severe cutaneous necrosis similar to that seen in coumarin skin necrosis. Protein S deficiency secondary to HAE and pregnancy was postulated. Treatment with heparin, C1-inhibitor concentrates, systemic steroids and surgical debridement resulted in a successful outcome for both mother and child. Subsequent investigations revealed normal levels of protein C, antithrombin III, total protein S, free protein S but reduced function protein S activity with evidence of activated protein C resistance. Cutaneous necrosis has not been reported in associated with activated protein C resistance previously and the possible mechanisms are discussed. PMID:7745572

  12. Slow versus fast

    OpenAIRE

    Siniscalchi, Valeria

    2013-01-01

    En s’appuyant sur le travail ethnographique mené par l’auteur depuis 2006 sur le fonctionnement et les dynamiques politiques et économiques de Slow Food (en France d’abord et dans le quartier général en Italie ensuite), l’analyse porte sur l’articulation entre la dimension politique du mouvement, sa philosophie et ses actions dans le champ de l’écologie. Créé en Italie au milieu des années 1980, Slow Food est devenu en moins de vingt ans un mouvement international qui regroupe près de cent mi...

  13. Increased and Prolonged Pulmonary Fibrosis in Surfactant Protein C-Deficient Mice Following Intratracheal Bleomycin

    OpenAIRE

    Lawson, William E.; Polosukhin, Vasiliy V.; Stathopoulos, Georgios T.; Zoia, Ornella; Han, Wei; Kirk B. Lane; Li, Bo; Donnelly, Edwin F.; Holburn, George E.; Lewis, Kenneth G.; Collins, Robert D.; Hull, William M.; Glasser, Stephan W.; Jeffrey A Whitsett; Blackwell, Timothy S.

    2005-01-01

    Recent reports have linked mutations in the surfactant protein C gene (SFTPC) to familial forms of pulmonary fibrosis, but it is uncertain whether deficiency of mature SP-C contributes to disease pathogenesis. In this study, we evaluated bleomycin-induced lung fibrosis in mice with genetic deletion of SFTPC. Compared with wild-type (SFTPC+/+) controls, mice lacking surfactant protein C (SFTPC−/−) had greater lung neutrophil influx at 1 week after intratracheal bleomycin, greater weight loss d...

  14. Portal vein thrombosis with protein C-S deficiency in a noncirrhotic patient

    Institute of Scientific and Technical Information of China (English)

    Gustavo; A; Rodríguez-Leal; Segundo; Morán; Roberto; Corona-Cedillo; Rocío; Brom-Valladares

    2014-01-01

    There are several conditions that can lead to portal vein thrombosis(PVT), including including infection, malignancies, and coagulation disorders. Anew condition of interest is protein C and S deficiencies, associated with hypercoagulation and recurrent venous thromboembolism. We report the case of a non-cirrhotic 63-year-old male diagnosed with acute superior mesenteric vein thrombosis and PVT and combined deficiencies in proteins C and S, recanalized by short-term low molecular heparin plus oral warfarin therapy.

  15. THE CLINICAL EXPRESSION OF HEREDITARY PROTEIN-C AND PROTEIN-S DEFICIENCY - A RELATION TO CLINICAL THROMBOTIC RISK-FACTORS AND TO LEVELS OF PROTEIN-C AND PROTEIN-S

    NARCIS (Netherlands)

    HENKENS, CMA; VANDERMEER, J; HILLEGE, JL; BOM, VJJ; HALIE, MR; van der Schaaf, W

    1993-01-01

    We investigated 103 first-degree relatives of 13 unrelated protein C or protein S deficient patients to assess the role of additional thrombotic risk factors and of protein C and protein S levels in the clinical expression of hereditary protein C and protein S deficiency. Fifty-seven relatives were

  16. Relationship between vitamin K dependent coagulation factors and anticoagulants (protein C and protein S) in neonatal vitamin K deficiency.

    OpenAIRE

    Matsuzaka, T; Tanaka, H.; Fukuda, M; Aoki, M.; Tsuji, Y; Kondoh, H

    1993-01-01

    To determine the relationship between vitamin K dependent coagulation factors and natural anticoagulants, namely protein C and protein S, in various degrees of vitamin K deficiency, plasma values for clotting activity, protein induced by vitamin K absence (PIVKA-II), protein C antigen, gamma-carboxy protein C antigen, and protein S antigen including total and free fractions and activity of protein C were measured in 66 full term and healthy breast fed neonates who did not receive vitamin K su...

  17. Evidence of a protein C-like anticoagulant system in bony fish.

    Science.gov (United States)

    Salte, R; Norberg, K; Odegaard, O R

    1996-09-01

    Evidence is presented, confirming the presence of an anticoagulant system in the plasma of Atlantic salmon (Salmo salar L) and rainbow trout (Oncorhynchus mykiss Walbaum) (Order: Teleostei, Family: Salmonidae) that bears striking similarities with the protein C anticoagulant system in mammals; its vitamin K-dependence was documented through a warfarin feeding trial. A potent activator of this system is the protein C activator from the venom of the Central American Moccasin, Agkistrodon bilineatus. When activated, the system splits the tripeptide substrate glu-pro-arg-pNa, which is the substrate preferred for the in vitro assay of human protein C. It also prolongates the plasma activated partial thromboplastin time, indicating that the system is of clinical relevance. A temperature dependence of the plasma protein C-like activity was evident, the mean activity being 5- to 10-fold higher, but also more variable, in both species in summer and early fall, than it was in winter. There was also a species difference, with rainbow trout having the higher levels. In man, subnormal values of protein C implies an increased risk of thrombosis. Whether this applies to fish is not known. It is, however, a fact that microvascular thromboses are prevalent in farmed Atlantic salmon in winter, whereas thrombotic disease is not a problem in rainbow trout; in the present study plasma protein C-like activity was 30% (of a human reference plasma) in salmon at 4 degrees C compared to a level of 60% in rainbow trout. A complicating factor for the assay of protein C-like activity in salmonid plasma, is the poor stability of the inhibitory system upon storage. Consequently, assays have to be done with freshly prepared citrated plasma. PMID:8873347

  18. Slow kaon beams

    International Nuclear Information System (INIS)

    A short description is given of considerations for the design of low-momentum kaon beam lines. Relevant data for the performance of seven existing and decommissioned slow kaon beams are presented. For single-stage separated beams the observed ratio all/K- is greater than 50 for momenta less than 500 MeV/c. We recommend a two-stage separated beam with perhaps an upstream cleanup section for maximal purity

  19. Activated protein C attenuates acute ischaemia reperfusion injury in skeletal muscle.

    LENUS (Irish Health Repository)

    Dillon, J P

    2012-02-03

    Activated protein C (APC) is an endogenous anti-coagulant with anti-inflammatory properties. The purpose of the present study was to evaluate the effects of activated protein C in the setting of skeletal muscle ischaemia reperfusion injury (IRI). IRI was induced in rats by applying rubber bands above the levels of the greater trochanters bilaterally for a period of 2h followed by 12h reperfusion. Treatment groups received either equal volumes of normal saline or activated protein C prior to tourniquet release. Following 12h reperfusion, muscle function was assessed electrophysiologically by electrical field stimulation. The animals were then sacrificed and skeletal muscle harvested for evaluation. Activated protein C significantly attenuated skeletal muscle reperfusion injury as shown by reduced myeloperoxidase content, wet to dry ratio and electrical properties of skeletal muscle. Further in vitro work was carried out on neutrophils isolated from healthy volunteers to determine the direct effect of APC on neutrophil function. The effects of APC on TNF-alpha stimulated neutrophils were examined by measuring CD18 expression as well as reactive oxygen species generation. The in vitro work demonstrated a reduction in CD18 expression and reactive oxygen species generation. We conclude that activated protein C may have a protective role in the setting of skeletal muscle ischaemia reperfusion injury and that this is in part mediated by a direct inhibitory effect on neutrophil activation.

  20. Levels of protein C and soluble thrombomodulin in critically ill patients with acute kidney injury: a multicenter prospective observational study.

    Directory of Open Access Journals (Sweden)

    Josée Bouchard

    Full Text Available Endothelial dysfunction contributes to the development of acute kidney injury (AKI in animal models of ischemia reperfusion injury and sepsis. There are limited data on markers of endothelial dysfunction in human AKI. We hypothesized that Protein C (PC and soluble thrombomodulin (sTM levels could predict AKI. We conducted a multicenter prospective study in 80 patients to assess the relationship of PC and sTM levels to AKI, defined by the AKIN creatinine (AKI Scr and urine output criteria (AKI UO. We measured marker levels for up to 10 days from intensive care unit admission. We used area under the curve (AUC and time-dependent multivariable Cox proportional hazard model to predict AKI and logistic regression to predict mortality/non-renal recovery. Protein C and sTM were not different in patients with AKI UO only versus no AKI. On intensive care unit admission, as PC levels are usually lower with AKI Scr, the AUC to predict the absence of AKI was 0.63 (95%CI 0.44-0.78. The AUC using log10 sTM levels to predict AKI was 0.77 (95%CI 0.62-0.89, which predicted AKI Scr better than serum and urine neutrophil gelatinase-associated lipocalin (NGAL and cystatin C, urine kidney injury molecule-1 and liver-fatty acid-binding protein. In multivariable models, PC and urine NGAL levels independently predicted AKI (p=0.04 and 0.02 and PC levels independently predicted mortality/non-renal recovery (p=0.04. In our study, PC and sTM levels can predict AKI Scr but are not modified during AKI UO alone. PC levels could independently predict mortality/non-renal recovery. Additional larger studies are needed to define the relationship between markers of endothelial dysfunction and AKI.

  1. Targeting the Anti-Apoptotic Protein c-FLIP for Cancer Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Safa, Ahmad R., E-mail: asafa@iupui.edu [Department of Pharmacology and Toxicology, Indiana University School of Medicine, 980 W. Walnut Street, R3-C524, Indianapolis, IN 46202 (United States); Indiana University Simon Cancer Center, Indiana University School of Medicine, 980 W. Walnut Street, R3-C524, Indianapolis, IN 46202 (United States); Pollok, Karen E. [Department of Pharmacology and Toxicology, Indiana University School of Medicine, 980 W. Walnut Street, R3-C524, Indianapolis, IN 46202 (United States); Indiana University Simon Cancer Center, Indiana University School of Medicine, 980 W. Walnut Street, R3-C524, Indianapolis, IN 46202 (United States); Herman B. Wells Center for Pediatric Research, 980 W. Walnut Street, R3-C524, Indianapolis, IN 46202 (United States)

    2011-03-29

    Cellular FLICE (FADD-like IL-1beta-converting enzyme)-inhibitory protein (c-FLIP) is a major resistance factor and critical anti-apoptotic regulator that inhibits tumor necrosis factor-alpha (TNF-alpha), Fas-L, and TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis as well as chemotherapy-triggered apoptosis in malignant cells. c-FLIP is expressed as long (c-FLIP{sub L}), short (c-FLIP{sub S}), and c-FLIP{sub R} splice variants in human cells. c-FLIP binds to FADD and/or caspase-8 or -10 in a ligand-dependent and-independent fashion, which in turn prevents death-inducing signaling complex (DISC) formation and subsequent activation of the caspase cascade. Moreover, c-FLIP{sub L} and c-FLIP{sub S} are known to have multifunctional roles in various signaling pathways, as well as activating and/or upregulating several cytoprotective signaling molecules. Upregulation of c-FLIP has been found in various tumor types, and its downregulation has been shown to restore apoptosis triggered by cytokines and various chemotherapeutic agents. Hence, c-FLIP is an important target for cancer therapy. For example, small interfering RNAs (siRNAs) that specifically knockdown the expression of c-FLIP{sub L} in diverse human cancer cell lines augmented TRAIL-induced DISC recruitment and increased the efficacy of chemotherapeutic agents, thereby enhancing effector caspase stimulation and apoptosis. Moreover, small molecules causing degradation of c-FLIP as well as decreasing mRNA and protein levels of c-FLIP{sub L} and c-FLIP{sub S} splice variants have been found, and efforts are underway to develop other c-FLIP-targeted cancer therapies. This review focuses on (1) the functional role of c-FLIP splice variants in preventing apoptosis and inducing cytokine and drug resistance; (2) the molecular mechanisms that regulate c-FLIP expression; and (3) strategies to inhibit c-FLIP expression and function.

  2. Go, Slow, and Whoa Foods

    Science.gov (United States)

    ... quick tips for seasonal health, safety and fun Go, Slow, and Whoa Foods Past Issues / Summer 2007 ... of California and Flaghouse, Inc. 2002 Food Group GO Almost anytime foods SLOW Sometimes foods WHOA Once ...

  3. Slowed Exports Growth

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The first half of 2010 is showing that the impacts of the financial crisis are still lingering.Zhao Jinping,a researcher at the Development Research Center of the State Council,says that the possible implementation of exit strategies in developed countries may deal a heavy blow to a global rally,and it will certainly result in slowed exports growth for China.Zhao published his opinion in the China Economic Times.The first part was published in issue No.33.Edited excerpts of the second part follow:

  4. Quantum gravity slows inflation

    Energy Technology Data Exchange (ETDEWEB)

    Tsamis, N.C. [Ecole Polytechnique, 91 - Palaiseau (France). Centre de Physique]|[Theory Group, FORTH, Heraklion, Crete (Greece); Woodard, R.P. [Florida Univ., Gainesville, FL (United States). Dept. of Physics

    1996-02-01

    We consider the quantum gravitational back-reaction on an initially inflating, homogeneous and isotropic universe whose topology is T{sup 3} {times} {Re}. Although there is no secular effect at one loop, an explicit calculation shows that two-loop processes act to slow the rate of expansion by an amount which becomes non-pertubatively large at late times. By exploiting Feynman`s tree theorem we show that all higher loops act in the same sense. 18 refs., 1 fig.

  5. Source modeling sleep slow waves

    OpenAIRE

    Murphy, M.; Riedner, B.A.; Huber, R.; Massimini, M; F. Ferrarelli; Tononi, G

    2009-01-01

    Slow waves are the most prominent electroencephalographic (EEG) feature of sleep. These waves arise from the synchronization of slow oscillations in the membrane potentials of millions of neurons. Scalp-level studies have indicated that slow waves are not instantaneous events, but rather they travel across the brain. Previous studies of EEG slow waves were limited by the poor spatial resolution of EEGs and by the difficulty of relating scalp potentials to the activity of the underlying cortex...

  6. Slowed Exports Growth

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    @@ Ⅲ. Slowed export recovery in the second half Since the beginning of this year, global trade has maintained a recovery growth thanks to the worldwide economic rally.From January to April, the imports of three major Economics--the United States, the euro zone and Japan--rose 17.5 percent on average from a year ago. Import growths for the United States, the euro zone and Japan were 20.9 percent, 4.8 percent and 29 percent, respectively, which spurred China's exports to those regions. From January to June this year, China's exports totaled $705.09 billion, up 35.2 percent from the same period in 2009 and were 5.8 percent higher than the first half of 2008 when the crisis had yet to begin. Those figures indicated China's exports had rebounded to precrisis levels.

  7. Hereditary thrombophilia: identification of nonsense and missense mutations in the protein C gene

    International Nuclear Information System (INIS)

    The structure of the gene for protein C, an anticoagulant serine protease, was analyzed in 29 unrelated patients with hereditary thrombophilia and protein C deficiency. Gene deletion(s) or gross rearrangement(s) was not demonstrable by Southern blot hybridization to cDNA probes. However, two unrelated patients showed a variant restriction pattern after Pvu II or BamHi digestion, due to mutations in the last exon: analysis of their pedigrees, including three or seven heterozygotes, respectively, with ∼50% reduction of both enzymatic and antigen level, showed the abnormal restriction pattern in all heterozygous individuals, but not in normal relatives. Cloning of protein C gene and sequencing of the last exon allowed the authors to identify a nonsense and a missense mutation, respectively. In the first case, codon 306 (CGA, arginine) is mutated to an inframe stop codon, thus generating a new Pvu II recognition site. In the second case, a missense mutation in the BamHI palindrome (GGATCC → GCATCC) leads to substitution of a key amino acid (a tryptophan to cysteine substitution at position 402), invariantly conserved in eukaryotic serine proteases. These point mutations may explain the protein C-deficiency phenotype of heterozygotes in the two pedigrees

  8. Human recombinant protein C for severe sepsis and septic shock in adult and paediatric patients

    DEFF Research Database (Denmark)

    Martí-Carvajal, Arturo J; Solà, Ivan; Gluud, Christian; Lathyris, Dimitrios; Cardona, Andrés Felipe

    2012-01-01

    Sepsis is a common and frequently fatal condition. Human recombinant activated protein C (APC) has been introduced to reduce the high risk of death associated with severe sepsis or septic shock. This systematic review is an update of a Cochrane review originally published in 2007....

  9. Recombinant activated protein C attenuates coagulopathy and inflammation when administered early in murine pneumococcal pneumonia

    NARCIS (Netherlands)

    M. Schouten; C. van 't Veer; J.J.T.H. Roelofs; B. Gerlitz; B.W. Grinnell; M. Levi; T. van der Poll

    2011-01-01

    Recombinant human activated protein C (APC), which has both anticoagulant and anti-inflammatory properties, improves survival of patients with severe sepsis. This beneficial effect is especially apparent in patients with pneumococcal pneumonia. Earlier treatment with APC in sepsis has been associate

  10. Anti-thrombin III, Protein C, and Protein S deficiency in acute coronary syndrome

    Directory of Open Access Journals (Sweden)

    Dasnan Ismail

    2002-06-01

    Full Text Available The final most common pathway for the majority of coronary artery disease is occlusion of a coronary vessel. Under normal conditions, antithrombin III (AT III, protein C, and protein S as an active protein C cofactor, are natural anticoagulants (hemostatic control that balances procoagulant activity (thrombin antithrombin complex balance to prevent thrombosis. If the condition becomes unbalanced, natural anticoagulants and the procoagulants can lead to thrombosis. Thirty subjects with acute coronary syndrome (ACS were studied for the incidence of antithrombin III (AT III, protein C, and protein S deficiencies, and the result were compare to the control group. Among patients with ACS, the frequency of distribution of AT-III with activity < 75% were 23,3% (7 of 30, and only 6,7% ( 2 of 30 in control subject. No one of the 30 control subject have protein C activity deficient, in ACS with activity < 70% were 13,3% (4 of 30. Fifteen out of the 30 (50% control subjects had protein S activity deficiency, while protein S deficiency activity < 70% was found 73.3.% (22 out of 30. On linear regression, the deterministic coefficient of AT-III activity deficiency to the development ACS was 13,25 %, and the deterministic coefficient of protein C activity deficient to the development of ACS was 9,06 %. The cut-off point for AT-III without protein S deficiency expected to contribute to the development of vessel disease was 45%. On discriminant analysis, protein C activity deficiency posed a risk for ACS of 4,5 greater than non deficient subjects, and AT-III activity deficiency posed a risk for ACS of 3,5 times greater than non deficient subjects. On binary logistic regression, protein S activity acted only as a reinforcing factor of AT-III activity deficiency in the development of ACS. Protein C and AT III deficiency can trigger ACS, with determinant coefficients of 9,06% and 13,25% respectively. Low levels of protein C posed a greater risk of

  11. A Case for Slow Reading

    Directory of Open Access Journals (Sweden)

    Matthew J Ostercamp

    2014-05-01

    Full Text Available This essay makes a case for the value of slow or deep reading.  Inspired by the Slow Food movement it seeks to apply their principles to reading.  It begins by exploring the meaning of information and how like food, information has come to be regarded as a commodity.  Drawing upon the philosophy of Albert Borgmann, it counters the prevalent commodity view of information by offering an alternative paradigm that connects careful reading to human flourishing.  It argues that by connecting information to pleasure and community, slow reading advocates can have comparable success to that enjoyed by the slow food movement.

  12. Mortality risk of untreated myosin-binding protein C-related hypertrophic cardiomyopathy: insight into the natural history

    NARCIS (Netherlands)

    E.A. Nannenberg; M. Michels; I. Christiaans; D. Majoor-Krakauer; Y.M. Hoedemaekers; J.P. van Tintelen; M.P. Lombardi; F.J. ten Cate; A.F.L. Schinkel; J.G.P. Tijssen; I.M. van Langen; A.A.M. Wilde; E.J.G. Sijbrands

    2011-01-01

    The goal of this study was to assess the mortality of hypertrophic cardiomyopathy (HCM), partly in times when the disease was not elucidated and patients were untreated. HCM is feared for the risk of sudden cardiac death (SCD). Insight in the natural history of the disorder is needed to design prope

  13. Recurrent Cerebral Infarctions in a Young Patient: Combined Protein C and S Deficiencies

    International Nuclear Information System (INIS)

    The possible etiologies of cerebral infarcts in young patients often present as diagnostic dilemmas as compared to older patients. Recently, deficiencies of fibrinolytic factors have emerged as an important etiology of stroke in the young population. Thrombophilic factors have been implicated in approximately 4 - 8% of the young strokes worldwide. Combined protein C and S deficiencies is a rare cause of recurrent ischaemic stroke in young population. Only a few sporadic cases have been reported in the literature. We are reporting a case of combined protein C and S deficiencyrelated recurrent ischaemic stroke in an 18 years old girl. Early diagnosis and targeted therapeutic management can help such patients to prevent recurrent thrombotic episodes. (author)

  14. Surfactant protein C-deficient mice are susceptible to respiratory syncytial virus infection

    OpenAIRE

    Glasser, Stephan W.; Witt, Teah L.; Senft, Albert P; Baatz, John E.; Folger, Dusti; Melissa D. Maxfield; Akinbi, Henry T.; Newton, Danforth A.; Prows, Daniel R.; Korfhagen, Thomas R.

    2009-01-01

    Patients with mutations in the pulmonary surfactant protein C (SP-C) gene develop interstitial lung disease and pulmonary exacerbations associated with viral infections including respiratory syncytial virus (RSV). Pulmonary infection with RSV caused more severe interstitial thickening, air space consolidation, and goblet cell hyperplasia in SP-C-deficient (Sftpc−/−) mice compared with SP-C replete mice. The RSV-induced pathology resolved more slowly in Sftpc−/− mice with lung inflammation per...

  15. Genetic replacement of surfactant protein-C reduces respiratory syncytial virus induced lung injury

    OpenAIRE

    Glasser, Stephan W.; Senft, Albert P; Melissa D. Maxfield; Ruetschilling, Teah L.; Baatz, John E.; Page, Kristen; Korfhagen, Thomas R.

    2013-01-01

    Background Individuals with deficiencies of pulmonary surfactant protein C (SP-C) develop interstitial lung disease (ILD) that is exacerbated by viral infections including respiratory syncytial virus (RSV). SP-C gene targeted mice (Sftpc -/-) lack SP-C, develop an ILD-like disease and are susceptible to infection with RSV. Methods In order to determine requirements for correction of RSV induced injury we have generated compound transgenic mice where SP-C expression can be induced on the Sftpc...

  16. Activated protein C promotes breast cancer cell migration through interactions with EPCR and PAR-1

    OpenAIRE

    Beaulieu, Lea M.; Church, Frank C.

    2006-01-01

    Activated protein C (APC) is a serine protease that regulates thrombin (IIa) production through inactivation of blood coagulation factors Va and VIIIa. APC also has non-hemostatic functions related to inflammation, proliferation, and apoptosis through various mechanisms. Using two breast cancer cell lines, MDA-MB-231 and MDA-MB-435, we investigated the role of APC in cell chemotaxis and invasion. Treatment of cells with increasing APC concentrations (1–50 μg/ml) increased invasion and chemota...

  17. Activated protein C: A regulator of human skin epidermal keratinocyte function

    Institute of Scientific and Technical Information of China (English)

    Kelly; McKelvey; Christopher; John; Jackson; Meilang; Xue

    2014-01-01

    Activated protein C(APC) is a physiological anticoagulant, derived from its precursor protein C(PC). Independent of its anticoagulation, APC possesses strong anti-inflammatory, anti-apoptotic and barrier protective properties which appear to be protective in a number of disorders including chronic wound healing. The epidermis is the outermost skin layer and provides the first line of defence against the external environment. Keratinocytes are the most predominant cells in the epidermis and play a critical role in maintaining epidermal barrier function. PC/APC and its receptor, endothelial protein C receptor(EPCR), once thought to be restricted to the endothelium, are abundantly expressed by skin epidermal keratinocytes. These cells respond to APC by upregulating proliferation, migration and matrix metalloproteinase-2 activity and inhibiting apoptosis/inflammation leading to a wound healing phenotype. APC also increases barrier function of keratinocyte monolayers by promoting the expression of tight junction proteins and re-distributing them to cell-cell contacts. These cytoprotective properties of APC are mediated through EPCR, protease-activated receptors, epidermal growth factor receptor or Tie2. Future preventive and therapeutic uses of APC in skin disorders associated with disruption of barrier function and inflammation look promising. This review will focus on APC’s function in skin epidermis/keratinocytes and its therapeutical potential in skin inflammatory conditions.

  18. Coagulation inhibitors and activated protein C resistance in recurrent pregnancy losses in Indian women

    Directory of Open Access Journals (Sweden)

    P Lalita Jyotsna

    2011-01-01

    Full Text Available Background: Thrombophilias, both acquired and inherited, have been investigated in the etiopathogenesis of unexplained recurrent pregnancy loss. Aim: To study coagulation inhibitors and activated protein C resistance (APCR in recurrent pregnancy losses (RPL occurring in second and third trimesters. Materials and Methods: A total of 30 pregnant women (group A with two or more recurrent unexplained fetal loses were evaluated for APCR, protein C deficiency, protein S deficiency, antithrombin deficiency, and antiphospholipid antibodies (APLA. Thirty age-matched controls were taken (group B comprising of pregnant women with at least one live issue. Statistical Analysis: Comparisons between two group frequencies and group means were made using Chi square test and Student′s t test, respectively. Results: Protein C and protein S levels were reduced in group A compared with group B and the difference was statistically significant (P=0.005 and P=0.032, respectively. The mean value of antithrombin was slightly reduced in group A compared with group B. APCR was observed in 16.6% cases and 3.3% controls. However, the difference was not statistically significant. APLA was observed in 20% cases and none of the controls. Of these, lupus anticoagulant was positive in 16.6% cases and anticardiolipin antibodies in 10% cases. Combined defects were seen in seven patients. Conclusion: There is a significant risk of RPL in pregnant women with thrombophilias. Therefore, screening for thrombophilias may be justified in pregnant women with unexplained recurrent fetal wastage, especially in second and third trimester.

  19. Symptomatic type 1 protein C deficiency caused by a de novo Ser270Leu mutation in the catalytic domain

    DEFF Research Database (Denmark)

    Lind, B; Koefoed, P; Thorsen, S

    2001-01-01

    , which is consistent with a type 1 deficiency. Transient expression of mutant protein C cDNA in human kidney 293 cells and analysis of protein C antigen in culture media and cell lysates showed that the secretion of mutant protein compared with wild-type protein was reduced by at least 97% while the...... the plasma protein C deficiency and are consistent with a disease mechanism that involves synthesis of mutant protein followed by intracellular degradation before its secretion into the extracellular space. The mutation was not present in the parents of the proband, suggesting a de novo mutation. Non...... intracellular content of mutant and wild-type protein was similar. Northern blot analysis of total mRNA from transfected cells showed no reduction of the mutant protein C mRNA compared with wild-type protein C mRNA. Collectively, these results indicate that the Ser270Leu mutation in the affected family caused...

  20. Slow Tourism: Exploring the discourses

    Directory of Open Access Journals (Sweden)

    J. Guiver

    2016-05-01

    Full Text Available ‘Slow travel’ and ‘slow tourism’ are relatively new, but contested, concepts. This paper examines the meanings ascribed to them in the academic literature and websites targeted at potential tourists. It finds concurrence on aspects of savouring time at the destination and investing time to appreciate the locality, its people, history, culture and products, but detects different emphases. The academic literature stresses the benefits to the destination and global sustainability, while the websites focus on the personal benefits and ways of becoming a ‘slow tourist’. Food and drink epitomise the immersion in and absorption of the destination and the multi-dimensional tourism experience, contrasted with the superficiality of mainstream tourism. The paper discusses whether tourists practising slow tourism without using the label are slow tourists or not.

  1. Slow dynamics and correlation functions

    OpenAIRE

    Halpern, V.

    2006-01-01

    The slow dynamics of a system as it approaches a phase transition, associated with the slowing down in the decay of a correlation function, can be caused by a sharp increase in the probability of a particle's returning to its original state following a transition, rather than to a slowing down in the transition rates as is usually assumed. The results of our calculations show that this is the case for the ferromagnetic Potts model. The implications of this result for various theories of the g...

  2. Microwave photonics: Harnessing slow light

    OpenAIRE

    Capmany J.; Gasulla I.; Sales S.

    2011-01-01

    Slow-light techniques originally conceived for buffering high-speed digital optical signals now look set to play an important role in providing broadband phase and true time delays for microwave signals.

  3. Influence of heparin and thromboplastin in half-life of 125I-protein C in rat blood

    International Nuclear Information System (INIS)

    The influence of heparin and thromboplastin on the halflife of 125I-protein C in rat blood was under investigation. The intravenous administration of heparin resulted in the prolongation of t1/2 to 6.5 h, that could be explained by inhibition of thrombin generation. Upon the 40-min infusion of thromboplastin the rate of 125I-protein C decay in blood enhanced. That could be explained by the generation of the endogenous thrombin and participation of thrombomodulin in the protein C activation as well as in the removal of the endogenous thrombin from blood

  4. Cold and Slow Molecular Beam

    OpenAIRE

    Rasmussen, Julia; Patterson, Dave; Lu, Hsin-I; Wright, Matthew; Doyle, John M.

    2011-01-01

    Employing a two-stage cryogenic buffer gas cell, we produce a cold, hydrodynamically extracted beam of calcium monohydride molecules with a near effusive velocity distribution. Beam dynamics, thermalization and slowing are studied using laser spectroscopy. The key to this hybrid, effusive-like beam source is a “slowing cell” placed immediately after a hydrodynamic, cryogenic source [Patterson et al., J. Chem. Phys., 2007, 126, 154307]. The resulting CaH beams are created in two regimes. In on...

  5. Slow Neutron Scattering by Benzene

    International Nuclear Information System (INIS)

    We have calculated the scattering of slow neutrons by the benzene molecule. The calculations are carried out within the framework of the time dependent formalism of Zemach and Glauber. Detailed account is taken of the effects of the molecular vibrations on the neutron scattering. Among the results explicitly calculated are the slow neutron total scattering cross-section as a function of energy and the energy angular distribution of singly scattered sections. (author)

  6. Slow motion increases perceived intent.

    Science.gov (United States)

    Caruso, Eugene M; Burns, Zachary C; Converse, Benjamin A

    2016-08-16

    To determine the appropriate punishment for a harmful action, people must often make inferences about the transgressor's intent. In courtrooms and popular media, such inferences increasingly rely on video evidence, which is often played in "slow motion." Four experiments (n = 1,610) involving real surveillance footage from a murder or broadcast replays of violent contact in professional football demonstrate that viewing an action in slow motion, compared with regular speed, can cause viewers to perceive an action as more intentional. This slow motion intentionality bias occurred, in part, because slow motion video caused participants to feel like the actor had more time to act, even when they knew how much clock time had actually elapsed. Four additional experiments (n = 2,737) reveal that allowing viewers to see both regular speed and slow motion replay mitigates the bias, but does not eliminate it. We conclude that an empirical understanding of the effect of slow motion on mental state attribution should inform the life-or-death decisions that are currently based on tacit assumptions about the objectivity of human perception. PMID:27482091

  7. Production and characterisation of recombinant forms of human pulmonary surfactant protein C (SP-C)

    DEFF Research Database (Denmark)

    Lukovic, Dunja; Plasencia, Inés; Taberner, Francisco J;

    2006-01-01

    recombinant SP-C variants so obtained retained more than 50% alpha-helical content and showed surface activity comparable to the native protein, as measured by surface spreading of lipid/protein suspensions and from compression pi-A isotherms of lipid/protein films. Compared to the protein purified from......Surfactant protein C (SP-C) is an essential component for the surface tension-lowering activity of the pulmonary surfactant system. It contains a valine-rich alpha helix that spans the lipid bilayer, and is one of the most hydrophobic proteins known so far. SP-C is also an essential component of...

  8. Renal Papillary Necrosis Caused by Protein C Deficiency Leading to Recurrent Hydronephrosis.

    Science.gov (United States)

    Chugh, Rohit Kumar; Olorunnisomo, Vincent; Fowle, Evan James; Modica, Ippolito; Meisels, Ira; Gupta, Mantu

    2016-01-01

    A patient with history of a solitary functioning kidney and protein C deficiency (PCD) presented with recurrent severe hydronephrosis causing acute kidney injury upon chronic kidney disease. Work-up with endoscopic evaluation revealed renal papillary necrosis (RPN) and sloughed renal papillae to be the true cause of the recurrent obstruction. Pathologic evaluation of the sloughed tissue confirmed the diagnosis of RPN. This is the first case reported in the literature illustrating the unique presentation of RPN in the setting of PCD. PMID:27579411

  9. Overexpression, purification and preliminary X-ray diffraction analysis of the controller protein C.Csp231I from Citrobacter sp. RFL231

    International Nuclear Information System (INIS)

    The crystallization of a novel controller protein is reported and its interaction with DNA is characterized. Restriction–modification controller proteins play an essential role in regulating the temporal expression of restriction–modification genes. The controller protein C.Csp231I represents a new class of controller proteins. The gene was sublconed to allow overexpression in Escherichia coli. The protein was purified to homogeneity and crystallized using the hanging-drop vapour-diffusion method. The crystals diffracted to 2.0 Å resolution and belonged to space group P21. An electrophoretic mobility-shift assay provided evidence of strong binding of C.Csp231I to a sequence located upstream of the csp231IC start codon

  10. Recombinant nematode anticoagulant protein c2 inhibits cell invasion by decreasing uPA expression in NSCLC cells.

    Science.gov (United States)

    Tong, Yu; Yue, Jun; Mao, Meng; Liu, Qingqing; Zhou, Jing; Yang, Jiyun

    2015-04-01

    Nematode anticoagulant protein c2 (NAPc2) is an 85-residue polypeptide originally isolated from the hematophagous hookworm, Ancylostoma caninum. Several studies have shown that rNAPc2 inhibits the growth of primary and metastatic tumors in mice independently of its ability to initiate coagulation. We obtained bioactive recombinant rNAPc2 by splicing of the rNAPc2-intein-CBD fusion proteins expressed in E. coli ER2566. In the in vitro assay, rNAPc2 obviously inhibited the invasive ability of non-small cell lung cancer (NSCLC) cells in a dose-dependent manner. Furthermore, rNAPc2 suppressed tumor growth in vivo by daily intraperitoneal injection of rNAPc2 in an NSCLC cell xenograft model of nude mice. Respectively, rNAPc2 downregulated the production of urokinase plasminogen activator (uPA) (P<0.05) and suppressed nuclear factor-κB (NF-κB) activity. We also identified that inhibition of NF-κB activity impaired cell invasion and reduced the uPA production in NSCLC cells. Meanwhile, NF-κB was found to directly bind to the uPA promoter in vitro. These results demonstrated that rNAPc2 inhibits cell invasion at least in part through the downregulation of the NF-κB-dependent metastasis-related gene expression in NSCLC. Our results also suggest that uPA, a known metastasis-promoting gene, is indirectly regulated by rNAPc2 through NF-κB activation. These results indicate that rNAPc2 may be a potent agent for the prevention of NSCLC progression. PMID:25672417

  11. The Potential of/for 'Slow': Slow Tourists and Slow Destinations

    Directory of Open Access Journals (Sweden)

    J. Guiver

    2016-05-01

    Full Text Available Slow tourism practices are nothing new; in fact, they were once the norm and still are for millions of people whose annual holiday is spent camping, staying in caravans, rented accommodation, with friends and relations or perhaps in a second home, who immerse themselves in their holiday environment, eat local food, drink local wine and walk or cycle around the area. So why a special edition about slow tourism? Like many aspects of life once considered normal (such as organic farming or free-range eggs, the emergence of new practices has highlighted differences and prompted a re-evaluation of once accepted practices and values. In this way, the concept of ‘slow tourism’ has recently appeared as a type of tourism that contrasts with many contemporary mainstream tourism practices. It has also been associated with similar trends already ‘branded’ slow: slow food and cittaslow (slow towns and concepts such as mindfulness, savouring and well-being.

  12. Increased and prolonged pulmonary fibrosis in surfactant protein C-deficient mice following intratracheal bleomycin.

    Science.gov (United States)

    Lawson, William E; Polosukhin, Vasiliy V; Stathopoulos, Georgios T; Zoia, Ornella; Han, Wei; Lane, Kirk B; Li, Bo; Donnelly, Edwin F; Holburn, George E; Lewis, Kenneth G; Collins, Robert D; Hull, William M; Glasser, Stephan W; Whitsett, Jeffrey A; Blackwell, Timothy S

    2005-11-01

    Recent reports have linked mutations in the surfactant protein C gene (SFTPC) to familial forms of pulmonary fibrosis, but it is uncertain whether deficiency of mature SP-C contributes to disease pathogenesis. In this study, we evaluated bleomycin-induced lung fibrosis in mice with genetic deletion of SFTPC. Compared with wild-type (SFTPC+/+) controls, mice lacking surfactant protein C (SFTPC-/-) had greater lung neutrophil influx at 1 week after intratracheal bleomycin, greater weight loss during the first 2 weeks, and increased mortality. At 3 and 6 weeks after bleomycin, lungs from SFTPC-/- mice had increased fibroblast numbers, augmented collagen accumulation, and greater parenchymal distortion. Furthermore, resolution of fibrosis was delayed. Although remodeling was near complete in SFTPC+/+ mice by 6 weeks, SFTPC-/- mice did not return to baseline until 9 weeks after bleomycin. By terminal dUTP nick-end labeling staining, widespread cell injury was observed in SFTPC-/- and SFTPC+/+ mice 1 week after bleomycin; however, ongoing apoptosis of epithelial and interstitial cells occurred in lungs of SFTPC-/- mice, but not SFTPC+/+ mice, 6 weeks after bleomycin. Thus, SP-C functions to limit lung inflammation, inhibit collagen accumulation, and restore normal lung structure after bleomycin. PMID:16251411

  13. Activated protein C inhibits neutrophil migration in allergic asthma: a randomised trial.

    Science.gov (United States)

    de Boer, J Daan; Berger, Marieke; Majoor, Christof J; Kager, Liesbeth M; Meijers, Joost C M; Terpstra, Sanne; Nieuwland, Rienk; Boing, Anita N; Lutter, René; Wouters, Diana; van Mierlo, Gerard J; Zeerleder, Sacha S; Bel, Elisabeth H; van't Veer, Cornelis; de Vos, Alex F; van der Zee, Jaring S; van der Poll, Tom

    2015-12-01

    Asthma patients show evidence of a procoagulant state in their airways, accompanied by an impaired function of the anticoagulant protein C system. We aimed to study the effect of recombinant human activated protein C (rhAPC) in allergic asthma patients.We conducted a randomised, double-blind, placebo-controlled, proof-of-concept study in house dust mite (HDM) allergic asthma patients. Patients were randomised to receive intravenous rhAPC (24 µg·kg(-1)·h(-1); n=12) or placebo (n=12) for 11 h. 4 h after the start of infusion, a first bronchoscopy was performed to challenge one lung segment with saline (control) and a contralateral segment with a combination of HDM extract and lipopolysaccharide (HDM+LPS), thereby mimicking environmental house dust exposure. A second bronchoscopy was conducted 8 h after intrabronchial challenge to obtain bronchoalveolar lavage fluid (BALF).rhAPC did not influence HDM+LPS induced procoagulant changes in the lung. In contrast, rhAPC reduced BALF leukocyte counts by 43% relative to placebo, caused by an inhibitory effect on neutrophil influx (64% reduction), while leaving eosinophil influx unaltered. rhAPC also reduced neutrophil degranulation products in the airways.Intravenous rhAPC attenuates HDM+LPS-induced neutrophil migration and protein release in allergic asthma patients by an effect that does not rely on coagulation inhibition. PMID:26381519

  14. Crystallization and preliminary crystallographic analysis of molybdenum-cofactor biosynthesis protein C from Thermus thermophilus

    International Nuclear Information System (INIS)

    The molybdenum-cofactor biosynthesis protein C from T. thermophilus has been crystallized in two different space groups, P21 and R32; the crystals diffracted to 1.9 and 1.75 Å resolution, respectively. The Gram-negative aerobic eubacterium Thermus thermophilus is an extremely important thermophilic microorganism that was originally isolated from a thermal vent environment in Japan. The molybdenum cofactor in this organism is considered to be an essential component required by enzymes that catalyze diverse key reactions in the global metabolism of carbon, nitrogen and sulfur. The molybdenum-cofactor biosynthesis protein C derived from T. thermophilus was crystallized in two different space groups. Crystals obtained using the first crystallization condition belong to the monoclinic space group P21, with unit-cell parameters a = 64.81, b = 109.84, c = 115.19 Å, β = 104.9°; the crystal diffracted to a resolution of 1.9 Å. The other crystal form belonged to space group R32, with unit-cell parameters a = b = 106.57, c = 59.25 Å, and diffracted to 1.75 Å resolution. Preliminary calculations reveal that the asymmetric unit contains 12 monomers and one monomer for the crystals belonging to space group P21 and R32, respectively

  15. Slow, stopped and stored light

    International Nuclear Information System (INIS)

    Light that can been slowed to walking pace could have applications in telecommunications, optical storage and quantum computing. Whether we use it to estimate how far away a thunderstorm is, or simply take it for granted that we can have a conversation with someone on the other side of the world, we all know that light travels extremely fast. Indeed, special relativity teaches us that nothing in the universe can ever move faster than the speed of light in a vacuum: 299 792 458 ms-1. However, there is no such limitation on how slowly light can travel. For the last few years, researchers have been routinely slowing light to just a few metres per second, and have recently even stopped it dead in its tracks so that it can be stored for future use. Slow-light has considerable popular appeal, deriving perhaps from the importance of the speed of light in relativity and cosmology. If everyday objects such as cars or people can travel faster than 'slow' light, for example, then it might appear that relativistic effects could be observed at very low speeds. Although this is not the case, slow light nonetheless promises to play an important role in optical technology because it allows light to be delayed for any period of time desired. This could lead to all-optical routers that would increase the bandwidth of the Internet, and applications in optical data storage, quantum information and even radar. (U.K.)

  16. Characterization of the protein C activator Protac from the venom of the southern copperhead (Agkistrodon contortrix) snake.

    Science.gov (United States)

    Stocker, K; Fischer, H; Meier, J; Brogli, M; Svendsen, L

    1987-01-01

    A single chain glycopeptide with a molecular weight of approximately 37,000, an isoelectric point of 3.0 +/- 0.2 and a carbohydrate content of approximately 20% was isolated from the venom of the southern copperhead Agkistrodon contortrix contortrix. It was capable of converting zymogen protein C in plasma of man and various vertebrates into its activated form, a serine proteinase which exerts an anticoagulant effect. Conversion of the zymogen protein C into the active proteinase was demonstrated by measuring the prolongation of the activated partial thromboplastin time due to proteolytic degradation of factors Va and VIIIa by the activation product, as well as by direct measurement of the generated enzyme activity by means of a synthetic chromogenic substrate. Intravenous injection of the venom protein C activator into rabbits caused prolonged activated partial thromboplastin time. Repeated subcutaneous injections led to formation of an antibody which formed, with purified protein C activator as well as with crude A. contortrix venom, a precipitating complex devoid of protein C activator potency. As revealed by activity measurements and by immunodiffusion experiments, the venoms of various A. contortrix, A. bilineatus subspecies contain similar protein C activators. PMID:3590209

  17. Two Mutations in Surfactant Protein C Gene Associated with Neonatal Respiratory Distress

    Directory of Open Access Journals (Sweden)

    Anna Tarocco

    2015-01-01

    Full Text Available Multiple mutations of surfactant genes causing surfactant dysfunction have been described. Surfactant protein C (SP-C deficiency is associated with variable clinical manifestations ranging from neonatal respiratory distress syndrome to lethal lung disease. We present an extremely low birth weight male infant with an unusual course of respiratory distress syndrome associated with two mutations in the SFTPC gene: C43-7G>A and 12T>A. He required mechanical ventilation for 26 days and was treated with 5 subsequent doses of surfactant with temporary and short-term efficacy. He was discharged at 37 weeks of postconceptional age without any respiratory support. During the first 16 months of life he developed five respiratory infections that did not require hospitalization. Conclusion. This mild course in our patient with two mutations is peculiar because the outcome in patients with a single SFTPC mutation is usually poor.

  18. Renal and urinary levels of endothelial protein C receptor correlate with acute renal allograft rejection.

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    Lionel Lattenist

    Full Text Available The Endothelial Protein C Receptor (EPCR is expressed on leukocytes, on endothelium of large blood vessels and to a lesser extent on capillaries. Membrane bound EPCR plays an important role in the activation of protein C which has anticoagulant, anti-inflammatory and cytoprotective effects. After cleavage by a protease EPCR is also found as a soluble protein. Acute rejection of kidney allografts can be divided in T-cell-mediated rejection (TCMR and antibody-mediated (ABMR rejection. The latter is characterized by strong activation of coagulation. Currently no reliable non-invasive biomarkers are available to monitor rejection. Renal biopsies were available from 81 renal transplant patients (33 without rejection, 26 TCMR and 22 ABMR, we had access to mRNA material, matched plasma and urine samples for a portion of this cohort. Renal EPCR expression was assessed by RT-PCR and immunostaining. Plasma and urine sEPCR levels were measured by ELISA. ABMR patients showed higher levels of EPCR mRNA than TCMR patients. EPCR expression on glomeruli was significantly elevated in ABMR patients than in TCMR or control patients. In the peritubular capillaries EPCR expression was higher in ABMR patients than in control patients. EPCR expression was higher in tubules and arteries of rejection patients than in control patients. Plasma sEPCR levels did not differ. Urine sEPCR levels were more elevated in the ABMR group than in patients with TCMR or without rejection. ROC analysis demonstrated that urinary sEPCR is appropriate to discriminate between ABMR patients and TCMR or control patients. We conclude that urinary sEPCR could be a novel non-invasive biomarker of antibody mediated rejection in renal transplantation.

  19. Numerical modeling of slow shocks

    International Nuclear Information System (INIS)

    This paper reviews previous attempt and the present status of efforts to understand the structure of slow shocks by means of time dependent numerical calculations. Studies carried out using MHD or hybrid-kinetic codes have demonstrated qualitative agreement with theory. A number of unresolved issues related to hybrid simulations of the internal shock structure are discussed in some detail. 43 refs., 8 figs

  20. The dynamics of slow manifolds

    NARCIS (Netherlands)

    Verhulst, F.; Bakri, T.

    2006-01-01

    Invited lecture at Konferensi Nasional Matematika XIII, Semarang, 24-27 juli, 2006; to be publ. in J. Indones. Math. Soc. (2007) After reviewing a number of results from geometric singular perturbation theory, we discuss several approaches to obtain periodic solutions in a slow manifold. Regarding n

  1. The unappreciated slowness of conventional tourism

    Directory of Open Access Journals (Sweden)

    G.R. Larsen

    2016-05-01

    Full Text Available Most tourists are not consciously engaging in ‘slow travel’, but a number of travel behaviours displayed by conventional tourists can be interpreted as slow travel behaviour. Based on Danish tourists’ engagement with the distances they travel across to reach their holiday destination, this paper explores unintended slow travel behaviours displayed by these tourists. None of the tourists participating in this research were consciously doing ‘slow travel’, and yet some of their most valued holiday memories are linked to slow travel behaviours. Based on the analysis of these unintended slow travel behaviours, this paper will discuss the potential this insight might hold for promotion of slow travel. If unappreciated and unintentional slow travel behaviours could be utilised in the deliberate effort of encouraging more people to travel slow, ‘slow travel’ will be in a better position to become integrated into conventional travel behaviour.

  2. Incoherent "Slow and Fast Light"

    CERN Document Server

    Zapasskii, V S

    2009-01-01

    We show experimentally that the effects of "slow and fast light" that are considered to be caused by spectral hole-burning under conditions of coherent population oscillations (CPO) can be universally observed with incoherent light fields on objects with the pure-intensity nonlinearity, when such an interpretation is inapplicable. As a light source, we used an incandescent lamp and as objects for study, a photochromic glass and a thermochromic coating. The response of the objects to intensity modulation of the incident light reproduced in all details the commonly accepted experimental evidences of the "light with a negative group velocity" and "ultraslow light". We come to conclusion that so far there are no experimental works providing evidence for real observation of the "CPO-based slow or fast light".

  3. Incoherent "Slow and Fast Light"

    OpenAIRE

    Zapasskii, V. S.; Kozlov, G. G.

    2009-01-01

    We show experimentally that the effects of "slow and fast light" that are considered to be caused by spectral hole-burning under conditions of coherent population oscillations (CPO) can be universally observed with incoherent light fields on objects with the pure-intensity nonlinearity, when such an interpretation is inapplicable. As a light source, we used an incandescent lamp and as objects for study, a photochromic glass and a thermochromic coating. The response of the objects to intensity...

  4. Evaluation of recombinant activated protein C for severe sepsis at a tertiary academic medical center

    Directory of Open Access Journals (Sweden)

    Anger KE

    2013-06-01

    Full Text Available Kevin E Anger,1 Jeremy R DeGrado,1 Bonnie C Greenwood,1 Steven A Cohen,2 Paul M Szumita1 1Department of Pharmacy, Brigham and Women’s Hospital, Boston, MA, USA; 2Department of Family Medicine and Population Health, Division of Epidemiology, Virginia Commonwealth University, Richmond, VA, USA Purpose: Early clinical trials of recombinant human activated protein C (rhAPC for severe sepsis excluded patients at high risk of bleeding. Recent literature suggests bleeding rates are higher in clinical practice and may be associated with worsened outcomes. Our objective was to evaluate baseline demographics; incidence, and risk factors for major bleeding; and mortality of patients receiving rhAPC for severe sepsis at our institution. Methods: A retrospective study was performed for all patients receiving rhAPC for treatment of severe sepsis at a tertiary academic medical center from January 2002 to June 2009. Demographic information, clinical variables, intensive care unit, and hospital outcomes were recorded. Results: Of the 156 patients that received rhAPC, 54 (34.6% did not meet institutional criteria for safe use at baseline due to bleeding precaution or contraindication. Twenty-three (14.7% patients experienced a major bleeding event. Multivariate analysis demonstrated baseline International Normalized Ratio ≥2.5 (odds ratio [OR] 3.68, 95% confidence interval [CI]: 1.28–10.56; P = 0.03 and platelet count ≤100 × 103/mm3 (OR 2.86, 95% CI: 1.07–7.67; P = 0.01 as significant predictors of a major bleed. Overall hospital mortality was 57.7%. Multivariate analysis demonstrated the presence of ≥3 organ dysfunctions (OR 2.46, 95% CI: 1.19–5.09; P < 0.05 and medical intensive care unit admission (OR 1.99, 95% CI: 1.00–3.98; P = 0.05 were independent variables associated with hospital mortality. Conclusion: Patients receiving rhAPC at our institution had higher APACHE II scores, mortality, and major bleeding events than published

  5. Neonatal arterial iliac thrombosis in type-I protein C deficiency: a case report

    Directory of Open Access Journals (Sweden)

    Capretti Maria G

    2010-03-01

    Full Text Available Abstract A male infant born by caesarean section at 38 weeks of gestational age (B.W. 4055 g; Apgar 9-10, in the first two hours of life his right leg became hypovascularizated. Normal values of leukocities, red cells, haematocrit, hemoglobin, platelets. C-Reactive Protein negative. Electrolytes and coagulation tests were normal. Normal vitamin K coagulation proteins levels. Serological tests for TORCH (IgM and Parvovirus (IgG and IgM were negative. Sonography showed a reduced blood flow in the iliac artery and reported a 1 cm long vessel thrombosis. From 8 hours of life we administred an intravenous infusion of unfractionated heparin (UFH 75 UI/Kg for the first 10 minutes then 28 UI/Kg/h. On the 2nd day tests were performed to assess absence of inhibiting-clot factors. The dosage of homocysteine, protein S and antithrombin was normal. FV Leiden and antiphospholipid antibodies were negative. The mapping of G20210A prothrombin's gene resulted normal, whereas the concentration of Protein C was lower than normal: activity 46% (68-150%, antigen 35% (70-150%. The same deficiency was also found in the father. The mother showed normal concentrations. No episodies of thrombosis events were documentated in the family. The intravenous unfractionated heparin (UFH therapy was replaced after 64 hours by subcutaneous nadroparin 600 UI twice/day, which was stopped 5 days later when the vessel sonografic images were completely normal. During the hospitalization the infant didn't show bleeding. The child was followed-up yearly until 4 years of age: he was well and had a normal body and mental development. The final diagnosis is likely to be of a permanent protein C deficiency in heterozygous form. Our case is interesting because the first manifestation was an important thrombosis of large vessel that occurred within a few hours of life in absence of perinatal risk factors, as if it was a homozygous disease, but the patient had a heterozygotic form. In literature

  6. Macrophage dysfunction and susceptibility to pulmonary Pseudomonas aeruginosa infection in surfactant protein C-deficient mice.

    Science.gov (United States)

    Glasser, Stephan W; Senft, Albert P; Whitsett, Jeffrey A; Maxfield, Melissa D; Ross, Gary F; Richardson, Theresa R; Prows, Daniel R; Xu, Yan; Korfhagen, Thomas R

    2008-07-01

    To determine the role of surfactant protein C (SP-C) in host defense, SP-C-deficient (Sftpc-/-) mice were infected with the pulmonary pathogen Pseudomonas aeruginosa by intratracheal injection. Survival of young, postnatal day 14 Sftpc-/- mice was decreased in comparison to Sftpc+/+ mice. The sensitivity to Pseudomonas bacteria was specific to the 129S6 strain of Sftpc-/- mice, a strain that spontaneously develops interstitial lung disease-like lung pathology with age. Pulmonary bacterial load and leukocyte infiltration were increased in the lungs of Sftpc-/- mice 24 h after infection. Early influx of polymorphonuclear leukocytes in the lungs of uninfected newborn Sftpc-/- mice relative to Sftpc+/+ mice indicate that the lack of SP-C promotes proinflammatory responses in the lung. Mucin expression, as indicated by Alcian blue staining, was increased in the airways of Sftpc-/- mice following infection. Phagocytic activity of alveolar macrophages from Sftpc-/- mice was reduced. The uptake of fluorescent beads in vitro and the number of bacteria phagocytosed by alveolar macrophages in vivo was decreased in the Sftpc-/- mice. Alveolar macrophages from Sftpc-/- mice expressed markers of alternative activation that are associated with diminished pathogen response and advancing pulmonary fibrosis. These findings implicate SP-C as a modifier of alveolar homeostasis. SP-C plays an important role in innate host defense of the lung, enhancing macrophage-mediated Pseudomonas phagocytosis, clearance and limiting pulmonary inflammatory responses. PMID:18566429

  7. Surfactant protein C-deficient mice are susceptible to respiratory syncytial virus infection.

    Science.gov (United States)

    Glasser, Stephan W; Witt, Teah L; Senft, Albert P; Baatz, John E; Folger, Dusti; Maxfield, Melissa D; Akinbi, Henry T; Newton, Danforth A; Prows, Daniel R; Korfhagen, Thomas R

    2009-07-01

    Patients with mutations in the pulmonary surfactant protein C (SP-C) gene develop interstitial lung disease and pulmonary exacerbations associated with viral infections including respiratory syncytial virus (RSV). Pulmonary infection with RSV caused more severe interstitial thickening, air space consolidation, and goblet cell hyperplasia in SP-C-deficient (Sftpc(-/-)) mice compared with SP-C replete mice. The RSV-induced pathology resolved more slowly in Sftpc(-/-) mice with lung inflammation persistent up to 30 days postinfection. Polymorphonuclear leukocyte and macrophage counts were increased in the bronchoalveolar lavage (BAL) fluid of Sftpc(-/-) mice. Viral titers and viral F and G protein mRNA were significantly increased in both Sftpc(-/-) and heterozygous Sftpc(+/-) mice compared with controls. Expression of Toll-like receptor 3 (TLR3) mRNA was increased in the lungs of Sftpc(-/-) mice relative to Sftpc(+/+) mice before and after RSV infection. Consistent with the increased TLR3 expression, BAL inflammatory cells were increased in the Sftpc(-/-) mice after exposure to a TLR3-specific ligand, poly(I:C). Preparations of purified SP-C and synthetic phospholipids blocked poly(I:C)-induced TLR3 signaling in vitro. SP-C deficiency increases the severity of RSV-induced pulmonary inflammation through regulation of TLR3 signaling. PMID:19304906

  8. Tumor suppressor protein C53 antagonizes checkpoint kinases to promote cyclin-dependent kinase 1 activation

    Institute of Scientific and Technical Information of China (English)

    Hai Jiang; Jianchun Wu; Chen He; Wending Yang; Honglin Li

    2009-01-01

    Cyclin-dependent kinase 1 (Cdk1)/cyclin B1 complex is the driving force for mitotic entry, and its activation is tightly regulated by the G2/M checkpoint. We originally reported that a novel protein C53 (also known as Cdk5rap3 and LZAP) potentiates DNA damage-induced cell death by modulating the G2/M checkpoint. More recently, Wang et al. (2007) found that C53/LZAP may function as a tumor suppressor by way of inhibiting NF-kB signaling. We report here the identification of C53 protein as a novel regulator of Cdk1 activation. We found that knockdown of C53 protein causes delayed Cdkl activation and mitotic entry. During DNA damage response, activation of checkpoint kinase 1 and 2 (Chk1 and Chk2) is partially inhibited by C53 overexpression. Intriguingly, we found that C53 interacts with Chkl and antagonizes its function. Moreover, a portion of C53 protein is localized at the centrosome, and centrosome-targeting C53 potently promotes local Cdk1 activation. Taken together, our results strongly suggest that C53 is a novel negative regulator of checkpoint response. By counteracting Chk1, C53 promotes Cdk1 activation and mitotic entry in both unperturbed cell-cycle progression and DNA damage response.

  9. Inhibitory effects of rutin on the endothelial protein C receptor shedding in vitro and in vivo.

    Science.gov (United States)

    Ku, Sae-Kwang; Lee, In-Chul; Han, Min-Su; Bae, Jong-Sup

    2014-10-01

    Endothelial cell protein C receptor (EPCR) has important functions in regulation of coagulation and inflammation. EPCR shedding from the cell surface is mediated by tumor necrosis factor-α converting enzyme (TACE). Rutin is one of the major flavonoids from the buckwheat plant Fagopyrum tataricum. In this study, we investigated the effects of rutin on phorbol-12-myristate 13-acetate (PMA), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and on cecal ligation and puncture (CLP)-mediated EPCR shedding. We used a CLP model because this model more closely resembles human sepsis. Data showed rutin was a potent inhibitor of PMA, TNF-α, IL-1β, and CLP-induced EPCR shedding by suppression of TACE expression. Treatment with rutin resulted in a decrease of PMA-stimulated phosphorylation of p38, extracellular regulated kinases 1/2, and c-Jun N-terminal kinase. These results suggest the potential application of rutin for treatment of PMA and CLP-mediated EPCR shedding. PMID:24622777

  10. Resistance to activated protein C is a risk factor for fibrostenosis in Crohn's disease

    Institute of Scientific and Technical Information of China (English)

    Gottfried Novacek; Wolfgang Miehsler; Julia Palkovits; Walter Reinisch; Thomas Waldh(o)r; Stylianos Kapiotis; Alfred Gangl; Harald Vogelsang

    2006-01-01

    AIM: To evaluate the effect of resistance to activated protein C (aPCR), the most common known inherited thrombophilic disorder, on the risk of intestinal operation of fibrostenosis in patients with Crohn's disease (CD).METHODS: In a previous study, we assessed the prevalence of aPCR in CD. In a retrospective casecontrolled study, 8 of these CD patients with aPCR were now compared with 24 CD patients without aPCR,matched by gender, age at diagnosis and duration of disease in a 1:3 fashion. The primary end point was the occurrence of an intestinal CD-related operation with evidence of fibrostenosis in the bowel resection specimen.RESULTS: The Kaplan-Meier analysis revealed that patients with aPCR had a lower probability of remaining free of operation with fibrostenosis than patients without aPCR (P = 0.0372; exact log-rank test) resulting in a significantly shorter median time interval from diagnosis of CD to the first operation with fibrostenosis (32 vs 160mo). At 10 years, the likelihood of remaining free of operation with fibrostenosis was 25% for patients with aPCR and 57.8% for patients without aPCR.CONCLUSION: CD patients with aPCR are at higher risk to undergo intestinal operation of fibrostenosis than those without aPCR. This supports our hypothesis of aPCR being a possible risk factor for fibrostenosis in CD.

  11. Barrier-protective effects of activated protein C in human alveolar epithelial cells.

    Directory of Open Access Journals (Sweden)

    Ferranda Puig

    Full Text Available Acute lung injury (ALI is a clinical manifestation of respiratory failure, caused by lung inflammation and the disruption of the alveolar-capillary barrier. Preservation of the physical integrity of the alveolar epithelial monolayer is of critical importance to prevent alveolar edema. Barrier integrity depends largely on the balance between physical forces on cell-cell and cell-matrix contacts, and this balance might be affected by alterations in the coagulation cascade in patients with ALI. We aimed to study the effects of activated protein C (APC on mechanical tension and barrier integrity in human alveolar epithelial cells (A549 exposed to thrombin. Cells were pretreated for 3 h with APC (50 µg/ml or vehicle (control. Subsequently, thrombin (50 nM or medium was added to the cell culture. APC significantly reduced thrombin-induced cell monolayer permeability, cell stiffening, and cell contraction, measured by electrical impedance, optical magnetic twisting cytometry, and traction microscopy, respectively, suggesting a barrier-protective response. The dynamics of the barrier integrity was also assessed by western blotting and immunofluorescence analysis of the tight junction ZO-1. Thrombin resulted in more elongated ZO-1 aggregates at cell-cell interface areas and induced an increase in ZO-1 membrane protein content. APC attenuated the length of these ZO-1 aggregates and reduced the ZO-1 membrane protein levels induced by thrombin. In conclusion, pretreatment with APC reduced the disruption of barrier integrity induced by thrombin, thus contributing to alveolar epithelial barrier protection.

  12. Activated protein C attenuates acute lung injury and apoptosis in a hyperoxic animal model.

    Science.gov (United States)

    Husari, Ahmad W; Khayat, Aline; Awdeh, Haitham; Hatoum, Hadi; Nasser, Michel; Mroueh, Salman M; Zaatari, Ghazi; El-Sabban, Marwan; Dbaibo, Ghassan S

    2010-05-01

    Evidence suggests that activated protein C (APC) attenuates acute lung injury (ALI) through antithrombotic and anti-inflammatory mechanisms. The aim of this study was to determine the effects of APC on ALI in adult rats exposed to hyperoxic environment. Rats were divided into control, hyperoxia, hyperoxia + APC, and APC. Hyperoxia and hyperoxia + APC were exposed to 1, 3, and 5 days of hyperoxia. Hyperoxia + APC and APC were injected with APC (5 mg/kg, i.p.) every 12 h. Control and hyperoxia received isotonic sodium chloride solution injection. Measurement of wet to dry ratio and albumin leak demonstrated significant improvement in hyperoxia + APC when compared with hyperoxia. Apoptosis, as measured by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay, was significantly reduced in hyperoxia + APC when compared with hyperoxia. Histological evaluation of lung sections showed significant reduction in inflammation, edema, and in the number of marginating neutrophils in hyperoxia + APC as compared with hyperoxia. Transcriptional expression of lung inflammatory mediators demonstrated a time-dependent surge in the levels TNF-alpha, IL-1beta, and IL-6 in response to hyperoxia that was attenuated with APC administration in the presence of hyperoxia. In this rat model, APC attenuates lung injury and the expression of inflammatory mediators in ALI secondary to hyperoxia. PMID:19851127

  13. Cloning and RNA interference analysis of the salivary protein C002 gene in Schizaphis graminum

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yong; FAN Jia; SUN Jing-rui; CHEN Ju-lian

    2015-01-01

    The ful-length cDNA of functional y-unknown salivary protein C002 in Schizaphis graminum was cloned using rapid am-pliifcation of cDNA ends (RACE) and designated as SgC002 (GenBank accession no. KC977563). It is 767 bp long and encodes a protein of 190 amino acid residues with a predicted mass of 21.5 kDa and a predicted cleavage site of N-ter-minal signal peptide between the 24th and the 25th residues. SgC002 is speciifcal y expressed in salivary gland with the highest level at the 2nd instar. Introducing SgC002-speciifc 476-siRNA, but not 546-siRNA to aphids through artiifcial diet signiifcantly suppressed SgC002 expression. Silencing SgC002 gene led to lethality of the aphid on wheat plants, but not on pure artiifcial diet. Our study demonstrated that artiifcial diet-mediated RNAi can be a useful tool for research on the roles of genes in aphid salivary gland, and also provided new insights into the characteristics of C002 in wheat aphids.

  14. Interaction of Pulmonary Surfactant Protein C with CD14 and Lipopolysaccharide

    OpenAIRE

    Augusto, Luis A.; Synguelakis, Monique; Johansson, Jan; Pedron, Thierry; Girard, Robert; Chaby, Richard

    2003-01-01

    In addition to their effects on alveolar surface tension, some components of lung surfactant also have immunological functions. We found recently that the hydrophobic lung surfactant protein SP-C specifically binds to the lipid A region of lipopolysaccharide (LPS). In this study, we show that SP-C also interacts with CD14. Four observations showed cross talk between the three molecules SP-C, LPS, and CD14. (i) Like LBP, SP-C allows the binding of a fluorescent LPS to cells expressing CD14 (th...

  15. Binding Procurement

    Science.gov (United States)

    Rao, Gopalakrishna M.; Vaidyanathan, Hari

    2007-01-01

    This viewgraph presentation reviews the use of the binding procurement process in purchasing Aerospace Flight Battery Systems. NASA Engineering and Safety Center (NESC) requested NASA Aerospace Flight Battery Systems Working Group to develop a set of guideline requirements document for Binding Procurement Contracts.

  16. Activated protein C ameliorates Bacillus anthracis lethal toxin-induced lethal pathogenesis in rats

    Directory of Open Access Journals (Sweden)

    Kau Jyh-Hwa

    2012-11-01

    Full Text Available Abstract Background Lethal toxin (LT is a major virulence factor of Bacillus anthracis. Sprague Dawley rats manifest pronounced lung edema and shock after LT treatments, resulting in high mortality. The heart failure that is induced by LT has been suggested to be a principal mechanism of lung edema and mortality in rodents. Since LT-induced death occurs more rapidly in rats than in mice, suggesting that other mechanisms in addition to the heart dysfunction may be contributed to the fast progression of LT-induced pathogenesis in rats. Coagulopathy may contribute to circulatory failure and lung injury. However, the effect of LT on coagulation-induced lung dysfunction is unclear. Methods To investigate the involvement of coagulopathy in LT-mediated pathogenesis, the mortality, lung histology and coagulant levels of LT-treated rats were examined. The effects of activated protein C (aPC on LT-mediated pathogenesis were also evaluated. Results Fibrin depositions were detected in the lungs of LT-treated rats, indicating that coagulation was activated. Increased levels of plasma D-dimer and thrombomodulin, and the ameliorative effect of aPC further suggested that the activation of coagulation-fibrinolysis pathways plays a role in LT-mediated pathogenesis in rats. Reduced mortality was associated with decreased plasma levels of D-dimer and thrombomodulin following aPC treatments in rats with LT-mediated pathogenesis. Conclusions These findings suggest that the activation of coagulation in lung tissue contributes to mortality in LT-mediated pathogenesis in rats. In addition, anticoagulant aPC may help to develop a feasible therapeutic strategy.

  17. A non-BRICHOS surfactant protein c mutation disrupts epithelial cell function and intercellular signaling

    Directory of Open Access Journals (Sweden)

    Beers Michael F

    2010-11-01

    Full Text Available Abstract Background Heterozygous mutations of SFTPC, the gene encoding surfactant protein C (SP-C, cause sporadic and familial interstitial lung disease (ILD in children and adults. The most frequent SFTPC mutation in ILD patients leads to a threonine for isoleucine substitution at position 73 (I73T of the SP-C preprotein (proSP-C, however little is known about the cellular consequences of SP-CI73T expression. Results To address this, we stably expressed SP-CI73T in cultured MLE-12 alveolar epithelial cells. This resulted in increased intracellular accumulation of proSP-C processing intermediates, which matched proSP-C species recovered in bronchial lavage fluid from patients with this mutation. Exposure of SP-CI73T cells to drugs currently used empirically in ILD therapy, cyclophosphamide, azathioprine, hydroxychloroquine or methylprednisolone, enhanced expression of the chaperones HSP90, HSP70, calreticulin and calnexin. SP-CI73T mutants had decreased intracellular phosphatidylcholine level (PC and increased lyso-PC level without appreciable changes of other phospholipids. Treatment with methylprednisolone or hydroxychloroquine partially restored these lipid alterations. Furthermore, SP-CI73T cells secreted into the medium soluble factors that modulated surface expression of CCR2 or CXCR1 receptors on CD4+ lymphocytes and neutrophils, suggesting a direct paracrine influence of SP-CI73T on neighboring cells in the alveolar space. Conclusion We show that I73T mutation leads to impaired processing of proSP-C in alveolar type II cells, alters their stress tolerance and surfactant lipid composition, and activates cells of the immune system. In addition, we show that some of the mentioned cellular aspects behind the disease can be modulated by application of pharmaceutical drugs commonly applied in the ILD therapy.

  18. Recombinant outer membrane protein C of Aeromonas hydrophila elicits mixed immune response and generates agglutinating antibodies.

    Science.gov (United States)

    Yadav, Sunita Kumari; Meena, Jitendra Kumar; Sharma, Mahima; Dixit, Aparna

    2016-08-01

    Aeromonas hydrophila is a gram-negative fish pathogenic bacterium, also responsible for causing opportunistic pathological conditions in humans. It causes a number of diseases in fish due to which the fish industry incurs huge economic losses annually. Due to problems of antibiotic resistance, and the rapidity with which the infection spreads among fishes, vaccination remains the most effective strategy to combat this infection in fish populations. Among various virulence factors associated with bacterial virulence, outer membrane proteins have been widely evaluated for their vaccine potential owing to their surface exposure and related role in pathogenicity. In the present study, we have investigated the immunogenic potential of a non-specific porin, outer membrane protein C (OmpC) whose expression is regulated by the two-component regulatory system and plays a major role in the survival of A. hydrophila under different osmolaric conditions. The full-length gene (~1 kb) encoding OmpC of A. hydrophila was cloned, characterized and expressed in E. coli. High yield (~112 mg/L at shake flask level) of the recombinant OmpC (rOmpC) (~40 kDa) of A. hydrophila was obtained upon purification from inclusion bodies using Ni(2+)-NTA affinity chromatography. Immunization with purified rOmpC in murine model generated high endpoint (>1:40,000) titers. IgG isotyping, ELISA and ELISPOT assay indicated mixed immune response with a TH2 bias. Also, the anti-rOmpC antibodies were able to agglutinate A. hydrophila in vitro and exhibited specific cross-reactivity with different Aeromonas strains, which will facilitate easy detection of different Aeromonas isolates in infected samples. Taken together, these data clearly indicate that rOmpC could serve as an effective vaccine against different strains of Aeromonas, a highly heterogenous group of bacteria. PMID:27328672

  19. Biological Variations of Lupus Anticoagulant, Antithrombin, Protein C, Protein S, and von Willebrand Factor Assays.

    Science.gov (United States)

    Shou, Weiling; Chen, Qian; Wu, Wei; Cui, Wei

    2016-02-01

    The results of lupus anticoagulant (LA), antithrombin (AT), protein C (PC), and protein S (PS) testing, and the values of von Willebrand factor antigen (VWF:Ag) are important in diagnosis and therapeutic monitoring of thrombosis and hemostasis diseases. Till now, no published study has focused on the biological variations in LA testing, and only a few studies have examined the biological variations of AT, PC, PS, and VWF:Ag. With the latest fully automated instruments and improved reagents, the analytical, within-subject, and between-subject biological variations were estimated for these five coagulant parameters in a cohort of 25 apparently healthy subjects. Blood specimens were collected at 8:00 am, 12:00 pm, and 4:00 pm on days 1, 3, and 5. The analytical biological variation (CV(A)) values of all the parameters were less than 3%. The within-subject biological variation (CV(W)) and between-subject biological variation (CV(G)) values of the LA normalized ratio were 4.64 and 6.83%, respectively. No significant differences were observed in the intraday and interday biological variations of LA tests, or in AT, PC, PS, and VWF:Ag values. Additionally, the utility of the conventional population-based reference intervals of the five coagulation parameters was evaluated by the index of individuality, and data on CV(W) and CV(A) were used to calculate the reference change value to identify the significance of changes in serial results from the same individual. PMID:26516946

  20. Centriolar CPAP/SAS-4 Imparts Slow Processive Microtubule Growth.

    Science.gov (United States)

    Sharma, Ashwani; Aher, Amol; Dynes, Nicola J; Frey, Daniel; Katrukha, Eugene A; Jaussi, Rolf; Grigoriev, Ilya; Croisier, Marie; Kammerer, Richard A; Akhmanova, Anna; Gönczy, Pierre; Steinmetz, Michel O

    2016-05-23

    Centrioles are fundamental and evolutionarily conserved microtubule-based organelles whose assembly is characterized by microtubule growth rates that are orders of magnitude slower than those of cytoplasmic microtubules. Several centriolar proteins can interact with tubulin or microtubules, but how they ensure the exceptionally slow growth of centriolar microtubules has remained mysterious. Here, we bring together crystallographic, biophysical, and reconstitution assays to demonstrate that the human centriolar protein CPAP (SAS-4 in worms and flies) binds and "caps" microtubule plus ends by associating with a site of β-tubulin engaged in longitudinal tubulin-tubulin interactions. Strikingly, we uncover that CPAP activity dampens microtubule growth and stabilizes microtubules by inhibiting catastrophes and promoting rescues. We further establish that the capping function of CPAP is important to limit growth of centriolar microtubules in cells. Our results suggest that CPAP acts as a molecular lid that ensures slow assembly of centriolar microtubules and, thereby, contributes to organelle length control. PMID:27219064

  1. A fast-slow logic system

    International Nuclear Information System (INIS)

    A fast-slow logic system has been made for use in multi-detector experiments in nuclear physics such as particle-gamma and particle-particle coincidence experiments. The system consists of a fast logic system and a slow logic system. The fast logic system has a function of fast coincidences and provides timing signals for the slow logic system. The slow logic system has a function of slow coincidences and a routing control of input analog signals to the ADCs. (auth.)

  2. Complement protein C1q induces maturation of human dendritic cells

    DEFF Research Database (Denmark)

    Cosmor, E; Bajtay, Z; Sándor, N;

    2007-01-01

    absence of antibodies, we undertook to investigate whether this complement protein has an impact on various functions of human DCs. Maturation of monocyte-derived immature DCs (imMDCs) cultured on immobilized C1q was followed by monitoring expression of CD80, CD83, CD86, MHCII and CCR7. The functional......Maturation of dendritic cells (DCs) is known to be induced by several stimuli, including microbial products, inflammatory cytokines and immobilized IgG, as demonstrated recently. Since immune complexes formed in vivo also contain C1q, moreover apoptotic cells and several pathogens fix C1q in the...... activity of the cells was assessed by measuring cytokine secretion and their ability to activate allogeneic T lymphocytes. Cytokine production by T cells co-cultured with C1q-matured DCs was also investigated. C1q, but not the structurally related mannose-binding lectin was found to bind to imMDC in a dose...

  3. The TTI slowness surface approximation

    KAUST Repository

    Stovas, A.

    2011-01-01

    The relation between the vertical and horizontal slownesses, better known as the dispersion relation, for a transversely isotropic media with titled symmetry axis {left parenthesis, less than bracket}TTI{right parenthesis, greater than bracket} requires solving a quartic polynomial, which does not admit a practical explicit solution to be used, for example, in downward continuation. Using a combination of perturbation theory with respect to the anelliptic parameter and Shanks transform to improve the accuracy of the expansion, we develop an explicit formula for the dispersion relation that is highly accurate for all practical purposes. It also reveals some insights into the anisotropy parameter dependency of the dispersion relation including the low impact that the anelliptic parameter has on the vertical placement of reflectors for small tilt in the symmetry angle. © 2011 Society of Exploration Geophysicists.

  4. Is cosmic acceleration slowing down?

    International Nuclear Information System (INIS)

    We investigate the course of cosmic expansion in its recent past using the Constitution SN Ia sample, along with baryon acoustic oscillations (BAO) and cosmic microwave background (CMB) data. Allowing the equation of state of dark energy (DE) to vary, we find that a coasting model of the universe (q0=0) fits the data about as well as Lambda cold dark matter. This effect, which is most clearly seen using the recently introduced Om diagnostic, corresponds to an increase of Om and q at redshifts z < or approx. 0.3. This suggests that cosmic acceleration may have already peaked and that we are currently witnessing its slowing down. The case for evolving DE strengthens if a subsample of the Constitution set consisting of SNLS+ESSENCE+CfA SN Ia data is analyzed in combination with BAO+CMB data. The effect we observe could correspond to DE decaying into dark matter (or something else).

  5. Plant domestication slows pest evolution.

    Science.gov (United States)

    Turcotte, Martin M; Lochab, Amaneet K; Turley, Nash E; Johnson, Marc T J

    2015-09-01

    Agricultural practices such as breeding resistant varieties and pesticide use can cause rapid evolution of pest species, but it remains unknown how plant domestication itself impacts pest contemporary evolution. Using experimental evolution on a comparative phylogenetic scale, we compared the evolutionary dynamics of a globally important economic pest - the green peach aphid (Myzus persicae) - growing on 34 plant taxa, represented by 17 crop species and their wild relatives. Domestication slowed aphid evolution by 13.5%, maintained 10.4% greater aphid genotypic diversity and 5.6% higher genotypic richness. The direction of evolution (i.e. which genotypes increased in frequency) differed among independent domestication events but was correlated with specific plant traits. Individual-based simulation models suggested that domestication affects aphid evolution directly by reducing the strength of selection and indirectly by increasing aphid density and thus weakening genetic drift. Our results suggest that phenotypic changes during domestication can alter pest evolutionary dynamics. PMID:26100381

  6. Slow pyrolysis of pistachio shell

    Energy Technology Data Exchange (ETDEWEB)

    Esin Apaydin-Varol; Ersan Putun; Ayse E. Putun [Anadolu University, Eskisehir (Turkey). Department of Chemical Engineering

    2007-08-15

    In this study, pistachio shell is taken as the biomass sample to investigate the effects of pyrolysis temperature on the product yields and composition when slow pyrolysis is applied in a fixed-bed reactor at atmospheric pressure to the temperatures of 300, 400, 500, 550, 700{sup o}C. The maximum liquid yield was attained at about 500-550{sup o}C with a yield of 20.5%. The liquid product obtained under this optimum temperature and solid products obtained at all temperatures were characterized. As well as proximate and elemental analysis for the products were the basic steps for characterization, column chromatography, FT-IR, GC/MS and SEM were used for further characterization. The results showed that liquid and solid products from pistachio shells show similarities with high value conventional fuels. 31 refs., 9 figs., 1 tab.

  7. Traditional Procurement is too Slow

    Directory of Open Access Journals (Sweden)

    Ann Kong

    2012-11-01

    Full Text Available This paper reports on an exploratory interview survey of construction project participants aimed at identifying the reasons for the decrease in use of the traditional, lump-sum, procurement system in Malaysia. The results show that most people believe it is too slow. This appears to be in part due to the contiguous nature of the various phase and stages of the process and especially the separation of the design and construction phases. The delays caused by disputes between the various parties are also seen as a contributory factor - the most prominent cause being the frequency of variations, with design and scope changes being a particular source of discontent. It is concluded that an up scaling of the whole of the time related reward/penalty system may be the most appropriate measure for the practice in future.

  8. A Double Slow Neutron Spectrometer

    International Nuclear Information System (INIS)

    The neutron spectrometer described in the paper is intended for measurements of the angular and energy distribution of monochromatic slow neutrons, inelasticaily scattered by liquid and solid bodies. Experiments of this type permit detailed information to be obtained concerning the dynamics of the atoms in various aggregate states of a substance. The spectromeeter is based on the time-of-flight method. The pulse source of neutrons is the IBR (1) reactor. A mechanical interrupter, rotating synchronously with the disc of the IBR and having a prescribed phase shift, serves as the monochromator. A special phasing system ensures a phasee stability better than 0.5o. The neutrons scattered by the sample are recorded by a scintillation detector set at a given angle to the neutron beam. The resolving power of the spectrometer is - 15 μs/m. The paper gives a detailed description of the construction of the spectroscope and its characteristics. (author)

  9. The endothelial protein C receptor rs867186-GG genotype is associated with increased soluble EPCR and could mediate protection against severe malaria.

    Science.gov (United States)

    Shabani, Estela; Opoka, Robert O; Bangirana, Paul; Park, Gregory S; Vercellotti, Gregory M; Guan, Weihua; Hodges, James S; Lavstsen, Thomas; John, Chandy C

    2016-01-01

    The endothelial protein C receptor (EPCR) appears to play an important role in Plasmodium falciparum endothelial cell binding in severe malaria (SM). Despite consistent findings of elevated soluble EPCR (sEPCR) in other infectious diseases, field studies to date have provided conflicting data about the role of EPCR in SM. To better define this role, we performed genotyping for the rs867186-G variant, associated with increased sEPCR levels, and measured sEPCR levels in two prospective studies of Ugandan children designed to understand immunologic and genetic factors associated with neurocognitive deficits in SM including 551 SM children, 71 uncomplicated malaria (UM) and 172 healthy community children (CC). The rs867186-GG genotype was more frequent in CC (4.1%) than SM (0.6%, P = 0.002). The rs867186-G variant was associated with increased sEPCR levels and sEPCR was lower in children with SM than CC (P < 0.001). Among SM children, those who had a second SM episode showed a trend toward lower plasma sEPCR both at initial admission and at 6-month follow-up compared to those without repeated SM (P = 0.06 for both). The study findings support a role for sEPCR in severe malaria pathogenesis and emphasize a distinct role of sEPCR in malaria as compared to other infectious diseases. PMID:27255786

  10. The endothelial protein C receptor rs867186-GG genotype is associated with increased soluble EPCR and could mediate protection against severe malaria

    Science.gov (United States)

    Shabani, Estela; Opoka, Robert O.; Bangirana, Paul; Park, Gregory S.; Vercellotti, Gregory M.; Guan, Weihua; Hodges, James S.; Lavstsen, Thomas; John, Chandy C.

    2016-01-01

    The endothelial protein C receptor (EPCR) appears to play an important role in Plasmodium falciparum endothelial cell binding in severe malaria (SM). Despite consistent findings of elevated soluble EPCR (sEPCR) in other infectious diseases, field studies to date have provided conflicting data about the role of EPCR in SM. To better define this role, we performed genotyping for the rs867186-G variant, associated with increased sEPCR levels, and measured sEPCR levels in two prospective studies of Ugandan children designed to understand immunologic and genetic factors associated with neurocognitive deficits in SM including 551 SM children, 71 uncomplicated malaria (UM) and 172 healthy community children (CC). The rs867186-GG genotype was more frequent in CC (4.1%) than SM (0.6%, P = 0.002). The rs867186-G variant was associated with increased sEPCR levels and sEPCR was lower in children with SM than CC (P malaria pathogenesis and emphasize a distinct role of sEPCR in malaria as compared to other infectious diseases. PMID:27255786

  11. Measurement of specific [3H]-ouabain binding to different types of human leucocytes

    DEFF Research Database (Denmark)

    Boon, Arnold; Oh, V M; Taylor, John E.; Johansen, Torben; Aronson, J K; Grahame-Smith, D G

    1984-01-01

    We have studied the specific binding of [3H]-ouabain to intact mononuclear leucocytes (82% lymphocytes) and polymorphonuclear leucocytes. In both types of cells [3H]-ouabain binding was saturable, confined to a single site of high affinity, slow to reach equilibrium, slow to reverse, temperature-...

  12. Recombinant human activated protein C inhibits local and systemic activation of coagulation without influencing inflammation during Pseudomonas aeruginosa pneumonia in rats

    NARCIS (Netherlands)

    Choi, Goda; Hofstra, Jorrit-Jan H; Roelofs, Joris J T H; Florquin, Sandrine; Bresser, Paul; Levi, Marcel; van der Poll, Tom; Schultz, Marcus J

    2007-01-01

    OBJECTIVE: Alveolar fibrin deposition is a hallmark of pneumonia. It has been proposed that recombinant human activated protein C exerts lung-protective effects via anticoagulant and anti-inflammatory pathways. We investigated the role of the protein C system in pneumonia caused by Pseudomonas aerug

  13. Levels of Protein C and Soluble Thrombomodulin in Critically Ill Patients with Acute Kidney Injury: A Multicenter Prospective Observational Study

    OpenAIRE

    Josée Bouchard; Rakesh Malhotra; Shamik Shah; Yu-Ting Kao; Florin Vaida; Akanksha Gupta; Berg, David T.; Grinnell, Brian W.; Brenda Stofan; Tolwani, Ashita J.; Mehta, Ravindra L

    2015-01-01

    Endothelial dysfunction contributes to the development of acute kidney injury (AKI) in animal models of ischemia reperfusion injury and sepsis. There are limited data on markers of endothelial dysfunction in human AKI. We hypothesized that Protein C (PC) and soluble thrombomodulin (sTM) levels could predict AKI. We conducted a multicenter prospective study in 80 patients to assess the relationship of PC and sTM levels to AKI, defined by the AKIN creatinine (AKI Scr) and urine output criteria ...

  14. Genetic Background Analysis of Protein C Deficiency Demonstrates a Recurrent Mutation Associated with Venous Thrombosis in Chinese Population

    OpenAIRE

    Tang, Liang; Guo, Tao; Yang, Rui; Mei, Heng; Wang, Huafang; Lu, Xuan; Yu, Jianming; Wang, Qingyun; Hu, Yu

    2012-01-01

    Background Protein C (PC) is one of the most important physiological inhibitors of coagulation proteases. Hereditary PC deficiency causes a predisposition to venous thrombosis (VT). The genetic characteristics of PC deficiency in the Chinese population remain unknown. Methods Thirty-four unrelated probands diagnosed with hereditary PC deficiency were investigated. PC activity and antigen levels were measured. Mutation analysis was performed by sequencing the PROC gene. In silico analyses, inc...

  15. Electronic Interactions of Slow Ions

    International Nuclear Information System (INIS)

    Full text: An investigation of the interaction of slow light ions with solids is of importance for surface science applications and fundamental understanding of electronic properties of different classes of materials. Knowledge of charge exchange processes is urgently required in quantitative surface analysis as applied in Low energy ion scattering (LEIS) experiments. These processes are linked to the electronic structure of the sample. The band structure of solids, in turn, influences the propagation of ions in matter, i. e. the inelastic energy loss due to electron hole pair excitation. Charge exchange processes like neutralization or reionization determine not only the ion yield in a LEIS experiment and thus its sensitivity, but also the probed information depth. Recent experiments have shown that the neutralization behaviour of noble gas ions scattered from single crystal surfaces is far from trivial and strong crystal effects have to be expected. Electron hole pair excitation along the trajectory gives rise to deceleration of the ion via electronic stopping power, S = -dE/dx, which - at least for a free electron gas - is assumed to be velocity proportional: S = Qv, as long v th is observed for H+ and He+, at vth ∼ 0.18 a.u., i.e. ∼4x105 m/s. Below vth only sp-electrons can be excited, while the d-electrons cannot, since the DOS of the d-electrons does not extend up to the Fermi level. For LiF with a band gap of 14 eV, electron-hole pairs can be excited by ions only if the velocity is larger than 0.09 a.u. Below, ions are slowed down only by atomic collisions. This threshold is lower than predicted. A similar behaviour was found for other ionic insulators with large band gaps, e.g. KCl. Comparison of the results for LiF and Cu or Au leads to the question why vth for insulators is so low. It might be concluded that the effective gap in LiF is ∼1 eV, in contrast to theoretical prediction. (author)

  16. Is cosmic acceleration slowing down?

    CERN Document Server

    Shafieloo, Arman; Starobinsky, Alexei A

    2009-01-01

    An investigation of dark energy (DE) using the Constitution SnIa sample (which includes recent CfA data at low redshifts) reveals a slight inconsistency (more than 1$\\sigma$) with the standard spatially flat LCDM model, if the assumption of a constant equation of state (w) for DE is dropped. This effect, which is most clearly seen using the recently introduced Om diagnostic, corresponds to an increase of Om and w at redshifts z<0.3. In geometrical terms, this suggests that cosmic acceleration may have already peaked and that we are currently witnessing its slowing down. Interestingly, such DE behaviour also provides a better fit to baryon acoustic oscillation (BAO) data. Including the cosmic microwave background (CMB) `shift parameter' as another independent observable, we show that the well known CPL parametrization is strained to fit the data simultaneously at low and high redshifts. This could either be because of the presence of systematics, or because the CPL ansatz is not versatile enough to catch th...

  17. Complement protein C3 exacerbates prion disease in a mouse model of chronic wasting disease.

    Science.gov (United States)

    Michel, Brady; Ferguson, Adam; Johnson, Theodore; Bender, Heather; Meyerett-Reid, Crystal; Wyckoff, A Christy; Pulford, Bruce; Telling, Glenn C; Zabel, Mark D

    2013-12-01

    Accumulating evidence shows a critical role of the complement system in facilitating attachment of prions to both B cells and follicular dendritic cells and assisting in prion replication. Complement activation intensifies disease in prion-infected animals, and elimination of complement components inhibits prion accumulation, replication and pathogenesis. Chronic wasting disease (CWD) is a highly infectious prion disease of captive and free-ranging cervid populations that utilizes the complement system for efficient peripheral prion replication and most likely efficient horizontal transmission. Here we show that complete genetic or transient pharmacological depletion of C3 prolongs incubation times and significantly delays splenic accumulation in a CWD transgenic mouse model. Using a semi-quantitative prion amplification scoring system we show that C3 impacts disease progression in the early stages of disease by slowing the rate of prion accumulation and/or replication. The delayed kinetics in prion replication correlate with delayed disease kinetics in mice deficient in C3. Taken together, these data support a critical role of C3 in peripheral CWD prion pathogenesis. PMID:24038599

  18. Synchronization Properties of Slow Cortical Oscillations

    Science.gov (United States)

    Takekawa, T.; Aoyagi, T.; Fukai, T.

    During slow-wave sleep, the brain shows slow oscillatory activity with remarkable long-range synchrony. Intracellular recordings show that the slow oscillation consists of two phases: an textit{up} state and a textit{down} state. Deriving the phase-response function of simplified neuronal systems, we examine the synchronization properties on slow oscillations between the textit{up} state and the textit{down} state. As a result, the strange interaction functions are found in some parameter ranges. These functions indicate that the states with the smaller phase lag than a critical value are all stable.

  19. Obsessional Slowness in College Students: Case Studies

    Science.gov (United States)

    Johnson, Aleta

    2014-01-01

    Cases of obsessional slowness, a variant of obsessive compulsive disorder, have been documented in case literature regarding relatively low functioning populations. However, obsessional slowness can also present in higher functioning populations, including college and graduate students, as illustrated here by three case examples from a competitive…

  20. 49 CFR 236.813 - Speed, slow.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Speed, slow. 236.813 Section 236.813 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Speed, slow. A speed not exceeding 20 miles per hour....

  1. Slow Movements of Bio-Inspired Limbs

    Science.gov (United States)

    Babikian, Sarine; Valero-Cuevas, Francisco J.; Kanso, Eva

    2016-05-01

    Slow and accurate finger and limb movements are essential to daily activities, but the underlying mechanics is relatively unexplored. Here, we develop a mathematical framework to examine slow movements of tendon-driven limbs that are produced by modulating the tendons' stiffness parameters. Slow limb movements are driftless in the sense that movement stops when actuations stop. We demonstrate, in the context of a planar tendon-driven system representing a finger, that the control of stiffness suffices to produce stable and accurate limb postures and quasi-static (slow) transitions among them. We prove, however, that stable postures are achievable only when tendons are pretensioned, i.e., they cannot become slack. Our results further indicate that a non-smoothness in slow movements arises because the precision with which individual stiffnesses need to be altered changes substantially throughout the limb's motion.

  2. Connecting slow earthquakes to huge earthquakes.

    Science.gov (United States)

    Obara, Kazushige; Kato, Aitaro

    2016-07-15

    Slow earthquakes are characterized by a wide spectrum of fault slip behaviors and seismic radiation patterns that differ from those of traditional earthquakes. However, slow earthquakes and huge megathrust earthquakes can have common slip mechanisms and are located in neighboring regions of the seismogenic zone. The frequent occurrence of slow earthquakes may help to reveal the physics underlying megathrust events as useful analogs. Slow earthquakes may function as stress meters because of their high sensitivity to stress changes in the seismogenic zone. Episodic stress transfer to megathrust source faults leads to an increased probability of triggering huge earthquakes if the adjacent locked region is critically loaded. Careful and precise monitoring of slow earthquakes may provide new information on the likelihood of impending huge earthquakes. PMID:27418504

  3. Structural and Functional Comparisons of Retroviral Envelope Protein C-Terminal Domains: Still Much to Learn

    Directory of Open Access Journals (Sweden)

    Jonathan D. Steckbeck

    2014-01-01

    Full Text Available Retroviruses are a family of viruses that cause a broad range of pathologies in animals and humans, from the apparently harmless, long-term genomic insertion of endogenous retroviruses, to tumors induced by the oncogenic retroviruses and acquired immunodeficiency syndrome (AIDS resulting from human immunodeficiency virus infection. Disease can be the result of diverse mechanisms, including tumorigenesis induced by viral oncogenes or immune destruction, leading to the gradual loss of CD4 T-cells. Of the virally encoded proteins common to all retroviruses, the envelope (Env displays perhaps the most diverse functionality. Env is primarily responsible for binding the cellular receptor and for effecting the fusion process, with these functions mediated by protein domains localized to the exterior of the virus. The remaining C-terminal domain may have the most variable functionality of all retroviral proteins. The C-terminal domains from three prototypical retroviruses are discussed, focusing on the different structures and functions, which include fusion activation, tumorigenesis and viral assembly and lifecycle influences. Despite these genetic and functional differences, however, the C-terminal domains of these viruses share a common feature in the modulation of Env ectodomain conformation. Despite their differences, perhaps each system still has information to share with the others.

  4. Overexpression of the endothelial protein C receptor is detrimental during pneumonia-derived gram-negative sepsis (Melioidosis.

    Directory of Open Access Journals (Sweden)

    Liesbeth M Kager

    Full Text Available BACKGROUND: The endothelial protein C receptor (EPCR enhances anticoagulation by accelerating activation of protein C to activated protein C (APC and mediates anti-inflammatory effects by facilitating APC-mediated signaling via protease activated receptor-1. We studied the role of EPCR in the host response during pneumonia-derived sepsis instigated by Burkholderia (B. pseudomallei, the causative agent of melioidosis, a common form of community-acquired Gram-negative (pneumosepsis in South-East Asia. METHODOLOGY/PRINCIPAL FINDINGS: Soluble EPCR was measured in plasma of patients with septic culture-proven melioidosis and healthy controls. Experimental melioidosis was induced by intranasal inoculation of B. pseudomallei in wild-type (WT mice and mice with either EPCR-overexpression (Tie2-EPCR or EPCR-deficiency (EPCR(-/-. Mice were sacrificed after 24, 48 or 72 hours. Organs and plasma were harvested to measure colony forming units, cellular influxes, cytokine levels and coagulation parameters. Plasma EPCR-levels were higher in melioidosis patients than in healthy controls and associated with an increased mortality. Tie2-EPCR mice demonstrated enhanced bacterial growth and dissemination to distant organs during experimental melioidosis, accompanied by increased lung damage, neutrophil influx and cytokine production, and attenuated coagulation activation. EPCR(-/- mice had an unremarkable response to B. pseudomallei infection as compared to WT mice, except for a difference in coagulation activation in plasma. CONCLUSION/SIGNIFICANCE: Increased EPCR-levels correlate with accelerated mortality in patients with melioidosis. In mice, transgenic overexpression of EPCR aggravates outcome during Gram-negative pneumonia-derived sepsis caused by B. pseudomallei, while endogenous EPCR does not impact on the host response. These results add to a better understanding of the regulation of coagulation during severe (pneumosepsis.

  5. Macrophage Dysfunction and Susceptibility to Pulmonary Pseudomonas aeruginosa Infection in Surfactant Protein C-Deficient Mice1

    OpenAIRE

    Glasser, Stephan W.; Senft, Albert P; Jeffrey A Whitsett; Melissa D. Maxfield; Ross, Gary F.; Richardson, Theresa R.; Prows, Daniel R.; Xu, Yan; Korfhagen, Thomas R.

    2008-01-01

    To determine the role of surfactant protein C (SP-C) in host defense, SP-C-deficient (Sftpc−/−) mice were infected with the pulmonary pathogen Pseudomonas aeruginosa by intratracheal injection. Survival of young, postnatal day 14 Sftpc−/−ice was decreased in comparison to Sftpc+/+ mice. The sensitivity to Pseudomonas bacteria was specific to the 129S6 strain of Sftpc−/− mice, a strain that spontaneously develops interstitial lung disease-like lung pathology with age. Pulmonary bacterial load ...

  6. The surfactant protein C mutation A116D alters cellular processing, stress tolerance, surfactant lipid composition, and immune cell activation

    OpenAIRE

    Zarbock Ralf; Woischnik Markus; Sparr Christiane; Thurm Tobias; Kern Sunčana; Kaltenborn Eva; Hector Andreas; Hartl Dominik; Liebisch Gerhard; Schmitz Gerd; Griese Matthias

    2012-01-01

    Abstract Background Surfactant protein C (SP-C) is important for the function of pulmonary surfactant. Heterozygous mutations in SFTPC, the gene encoding SP-C, cause sporadic and familial interstitial lung disease (ILD) in children and adults. Mutations mapping to the BRICHOS domain located within the SP-C proprotein result in perinuclear aggregation of the proprotein. In this study, we investigated the effects of the mutation A116D in the BRICHOS domain of SP-C on cellular homeostasis. We al...

  7. Platelets in inflammation : Role of complement protein C1q, C-reactive proteinand toll-like receptors

    OpenAIRE

    Skoglund, Caroline

    2010-01-01

    Platelets are proven essential in haemostasis, however, they are now also increasingly recognized as cells with important immunomodulatory properties, e.g. through interaction with leukocytes and several species of bacteria and by release inflammatory mediators upon activation. Moreover, platelets express receptors involved in immunity and inflammation such as Fcγ‐receptor IIa, complement protein C1q‐receptors (gC1qR, cC1qR, CD93 and α2β1) and toll‐like receptors (TLR‐1, ‐2, ‐4, ‐6 and ‐9). C...

  8. Large Deviations in Fast-Slow Systems

    Science.gov (United States)

    Bouchet, Freddy; Grafke, Tobias; Tangarife, Tomás; Vanden-Eijnden, Eric

    2016-02-01

    The incidence of rare events in fast-slow systems is investigated via analysis of the large deviation principle (LDP) that characterizes the likelihood and pathway of large fluctuations of the slow variables away from their mean behavior—such fluctuations are rare on short time-scales but become ubiquitous eventually. Classical results prove that this LDP involves an Hamilton-Jacobi equation whose Hamiltonian is related to the leading eigenvalue of the generator of the fast process, and is typically non-quadratic in the momenta—in other words, the LDP for the slow variables in fast-slow systems is different in general from that of any stochastic differential equation (SDE) one would write for the slow variables alone. It is shown here that the eigenvalue problem for the Hamiltonian can be reduced to a simpler algebraic equation for this Hamiltonian for a specific class of systems in which the fast variables satisfy a linear equation whose coefficients depend nonlinearly on the slow variables, and the fast variables enter quadratically the equation for the slow variables. These results are illustrated via examples, inspired by kinetic theories of turbulent flows and plasma, in which the quasipotential characterizing the long time behavior of the system is calculated and shown again to be different from that of an SDE.

  9. Slow light Mach-Zehnder fiber interferometer

    Institute of Scientific and Technical Information of China (English)

    Yundong Zhang; Jinfang Wang; Xuenan Zhang; Hao Wu; Yuanxue Cai; Jing Zhang; Ping Yuan

    2012-01-01

    A slow light structure Mach-Zehnder fiber interferometer is theoretically demonstrated.The sensitivity of the interferometer is significantly enhanced by the dispersion of the slow light structure.The numerical results show that the sensitivity enhancement factor varies with the coupling coefficient and reaches its maximum under critical coupling conditions.Interferometers have been investigated in relation to their applications in fields such as metrology[1],optical sensing[2],optical communication[3,4],quantum information processing[5],and biomedical engineering[6].A number of schemes have been proposed to improve the performance of interferometers[7],such as using photonic crystal structures to minimize the size of on-chip devices[8],utilizing the dispersive property of semiconductor to enhance the spectral sensitivity of interferometers[9,10],utilizing slow light medium to enhance the resolution of Fourier transform interferometer[11],exploiting fast light medium or slow light structure to increase the rotation sensitivity of a Sagnac interferometer[12,13],enhancing the transmittance of the Mach-Zehnder interferometer (MZI) in the slow light region by gratings[14],and using liquid crystal light valve to derive high sensitivity interferometers[15].%A slow light structure Mach-Zehnder fiber interferometer is theoretically demonstrated. The sensitivity of the interferometer is significantly enhanced by the dispersion of the slow light structure. The numerical results show that the sensitivity enhancement factor varies with the coupling coefficient and reaches its maximum under critical coupling conditions.

  10. KEK-IMSS Slow Positron Facility

    Energy Technology Data Exchange (ETDEWEB)

    Hyodo, T; Wada, K; Yagishita, A; Kosuge, T; Saito, Y; Kurihara, T; Kikuchi, T; Shirakawa, A; Sanami, T; Ikeda, M; Ohsawa, S; Kakihara, K; Shidara, T, E-mail: toshio.hyodo@kek.jp [High Energy Accelerator Research Organization (KEK) 1-1 Oho, Tsukuba, Ibaraki, 305-0801 (Japan)

    2011-12-01

    The Slow Positron Facility at the Institute of Material Structure Science (IMSS) of High Energy Accelerator Research Organization (KEK) is a user dedicated facility with an energy tunable (0.1 - 35 keV) slow positron beam produced by a dedicated 55MeV linac. The present beam line branches have been used for the positronium time-of-flight (Ps-TOF) measurements, the transmission positron microscope (TPM) and the photo-detachment of Ps negative ions (Ps{sup -}). During the year 2010, a reflection high-energy positron diffraction (RHEPD) measurement station is going to be installed. The slow positron generator (converter/ moderator) system will be modified to get a higher slow positron intensity, and a new user-friendly beam line power-supply control and vacuum monitoring system is being developed. Another plan for this year is the transfer of a {sup 22}Na-based slow positron beam from RIKEN. This machine will be used for the continuous slow positron beam applications and for the orientation training of those who are interested in beginning researches with a slow positron beam.

  11. KEK-IMSS Slow Positron Facility

    International Nuclear Information System (INIS)

    The Slow Positron Facility at the Institute of Material Structure Science (IMSS) of High Energy Accelerator Research Organization (KEK) is a user dedicated facility with an energy tunable (0.1 - 35 keV) slow positron beam produced by a dedicated 55MeV linac. The present beam line branches have been used for the positronium time-of-flight (Ps-TOF) measurements, the transmission positron microscope (TPM) and the photo-detachment of Ps negative ions (Ps-). During the year 2010, a reflection high-energy positron diffraction (RHEPD) measurement station is going to be installed. The slow positron generator (converter/ moderator) system will be modified to get a higher slow positron intensity, and a new user-friendly beam line power-supply control and vacuum monitoring system is being developed. Another plan for this year is the transfer of a 22Na-based slow positron beam from RIKEN. This machine will be used for the continuous slow positron beam applications and for the orientation training of those who are interested in beginning researches with a slow positron beam.

  12. Insulin binding to individual rat skeletal muscles

    International Nuclear Information System (INIS)

    Studies of insulin binding to skeletal muscle, performed using sarcolemmal membrane preparations or whole muscle incubations of mixed muscle or typical red (soleus, psoas) or white [extensor digitorum longus (EDL), gastrocnemius] muscle, have suggested that red muscle binds more insulin than white muscle. We have evaluated this hypothesis using cryostat sections of unfixed tissue to measure insulin binding in a broad range of skeletal muscles; many were of similar fiber-type profiles. Insulin binding per square millimeter of skeletal muscle slice was measured by autoradiography and computer-assisted densitometry. We found a 4.5-fold range in specific insulin tracer binding, with heart and predominantly slow-twitch oxidative muscles (SO) at the high end and the predominantly fast-twitch glycolytic (FG) muscles at the low end of the range. This pattern reflects insulin sensitivity. Evaluation of displacement curves for insulin binding yielded linear Scatchard plots. The dissociation constants varied over a ninefold range (0.26-2.06 nM). Binding capacity varied from 12.2 to 82.7 fmol/mm2. Neither binding parameter was correlated with fiber type or insulin sensitivity; e.g., among three muscles of similar fiber-type profile, the EDL had high numbers of low-affinity binding sites, whereas the quadriceps had low numbers of high-affinity sites. In summary, considerable heterogeneity in insulin binding was found among hindlimb muscles of the rat, which can be attributed to heterogeneity in binding affinities and the numbers of binding sites. It can be concluded that a given fiber type is not uniquely associated with a set of insulin binding parameters that result in high or low binding

  13. Plasmin cleaves fibrinogen and the human complement proteins C3b and C5 in the presence of Leptospira interrogans proteins: A new role of LigA and LigB in invasion and complement immune evasion.

    Science.gov (United States)

    Castiblanco-Valencia, Mónica Marcela; Fraga, Tatiana Rodrigues; Pagotto, Ana Helena; de Toledo Serrano, Solange Maria; Abreu, Patricia Antonia Estima; Barbosa, Angela Silva; Isaac, Lourdes

    2016-05-01

    Plasminogen is a single-chain glycoprotein found in human plasma as the inactive precursor of plasmin. When converted to proteolytically active plasmin, plasmin(ogen) regulates both complement and coagulation cascades, thus representing an important target for pathogenic microorganisms. Leptospira interrogans binds plasminogen, which is converted to active plasmin. Leptospiral immunoglobulin-like (Lig) proteins are surface exposed molecules that interact with extracellular matrix components and complement regulators, including proteins of the FH family and C4BP. In this work, we demonstrate that these multifunctional molecules also bind plasminogen through both N- and C-terminal domains. These interactions are dependent on lysine residues and are affected by ionic strength. Competition assays suggest that plasminogen does not share binding sites with C4BP or FH on Lig proteins at physiological molar ratios. Plasminogen bound to Lig proteins is converted to proteolytic active plasmin in the presence of urokinase-type plasminogen activator (uPA). Lig-bound plasmin is able to cleave the physiological substrates fibrinogen and the complement proteins C3b and C5. Taken together, our data point to a new role of LigA and LigB in leptospiral invasion and complement immune evasion. Plasmin(ogen) acquisition by these versatile proteins may contribute to Leptospira infection, favoring bacterial survival and dissemination inside the host. PMID:26822552

  14. Comparison of pathways from the geometric targeting method and targeted molecular dynamics in nitrogen regulatory protein C

    International Nuclear Information System (INIS)

    Geometric targeting (GT) is a recently introduced method for rapidly generating all-atom pathways from one protein state to another, based on geometric rather than energetic considerations. To generate pathways, a bias is applied that gradually moves atoms toward a target structure, while a set of geometric constraints between atoms is enforced to keep the structure stereochemically acceptable. In this work, we compare conformational pathways generated from GT to pathways from the much more computationally intensive and commonly used targeted molecular dynamics (TMD) technique, for a complicated conformational change in the signaling protein nitrogen regulatory protein C. We show that the all-atom pathways from GT are similar to previously reported TMD pathways for this protein, by comparing motion along six progress variables that describe the various structural changes. The results suggest that for nitrogen regulatory protein C, finding an all-atom pathway is primarily a problem of geometry, and that a detailed force field in this case constitutes an unnecessary extra layer of detail. We also show that the pathway snapshots from GT have good structure quality, by measuring various structure quality metrics. Transient hydrogen bonds detected by the two methods show some similarities but also some differences. The results justify the usage of GT as a rapid, approximate alternative to TMD for generating stereochemically acceptable all-atom pathways in highly constrained protein systems

  15. Mutation-Specific Phenotypes in hiPSC-Derived Cardiomyocytes Carrying Either Myosin-Binding Protein C Or α-Tropomyosin Mutation for Hypertrophic Cardiomyopathy

    OpenAIRE

    Marisa Ojala; Chandra Prajapati; Risto-Pekka Pölönen; Kristiina Rajala; Mari Pekkanen-Mattila; Jyrki Rasku; Kim Larsson; Katriina Aalto-Setälä

    2015-01-01

    Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disease, which affects the structure of heart muscle tissue. The clinical symptoms include arrhythmias, progressive heart failure, and even sudden cardiac death but the mutation carrier can also be totally asymptomatic. To date, over 1400 mutations have been linked to HCM, mostly in genes encoding for sarcomeric proteins. However, the pathophysiological mechanisms of the disease are still largely unknown. Two founder mutations for HCM in ...

  16. Novel Phenotype–Genotype Correlations of Restrictive Cardiomyopathy With Myosin-Binding Protein C (MYBPC3) Gene Mutations Tested by Next-Generation Sequencing

    OpenAIRE

    Wu, Wei; Lu, Chao-Xia; Wang, Yi-Ning; Liu, Fang; Chen, Wei; Liu, Yong-Tai; Han, Ye-Chen; Cao, Jian; Zhang, Shu-Yang; Zhang, Xue

    2015-01-01

    Background MYBPC3 dysfunctions have been proven to induce dilated cardiomyopathy, hypertrophic cardiomyopathy, and/or left ventricular noncompaction; however, the genotype–phenotype correlation between MYBPC3 and restrictive cardiomyopathy (RCM) has not been established. The newly developed next-generation sequencing method is capable of broad genomic DNA sequencing with high throughput and can help explore novel correlations between genetic variants and cardiomyopathies. Methods and Results ...

  17. Internal stress drives slow glassy dynamics and quake-like behaviour in ionotropic pectin gels.

    Science.gov (United States)

    Mansel, Bradley W; Williams, Martin A K

    2015-09-21

    Frustrated, out-of-equilibrium materials have been of considerable interest for some time and continue to be some of the least understood materials. Recent measurements have shown that many gelled biopolymer materials display slow dynamics on timescales greater than one second, that are not accessible with typical methods, and are characteristic of glassy trapped systems. In this study we have controlled the fine structure of the anionic polysaccharide pectin in order to construct a series of ionotropic gels having differing binding energies between the constituent chains, in an attempt to further understand the slow dynamical processes occurring. Using multi-speckle light scattering techniques it is shown that the slow dynamics observed in these gelled systems are stress-driven. As the binding lengths, and thus the binding energies, of the junction zones between the polymer chains in these networks increase the long-time dynamics initially slow, as might be expected, until a critical level of internal stress is reached upon which the dynamics increase significantly, with gentle creaking punctuated by localised stress-relieving quakes. PMID:26242797

  18. Slow living and the green economy

    Directory of Open Access Journals (Sweden)

    Diana-Eugenia Ioncică

    2016-05-01

    Full Text Available The current paper explores the relationship between some relatively new concepts in the field of economics – slow living, slow food, slow writing and the green economy. The goal of the paper is twofold – discussing the possibilities opened by these exciting new concepts, in terms of an increase in the quality of life combined with an environmentally sustainable lifestyle, as well as ascertaining what the concepts may entail in the context in which the effects of the recent economic crisis may make green and slow living seem like a distant dream. It is this holistic view that we shall attempt to enlarge upon in the paper, with the avowed purpose of weighing out the possibilities presented in the complicated, crisis-fraught global context.

  19. Development of slowed down beams at GSI

    International Nuclear Information System (INIS)

    The NUSTAR/HISPEC slowed down beam project at GSI/FAIR is dedicated to rare isotopes with energies of upto 10 MeV/u. These radioactive beams will be used for spectroscopy and reactions studies. The setup for slowing down will utilize a thick degrader positioned after the FRS/Super-FRS separators at GSI/FAIR, followed by transmission detectors for energy and trajectory reconstruction. As a test, Coulomb excitation of a slowed down 64Ni beam on a gold target was performed in Sep-Oct 2008 at GSI. TPC and MCP detectors were used for the tracking of the beam before and after slowing it down. The gold target, placed after the tracking setup, was surrounded partially with two DSSSDs and NaI γ-detectors. The results from the test experiment and a comparison to simulations are presented.

  20. Response of electret dosemeter to slow neutrons

    International Nuclear Information System (INIS)

    The response of the electret dosemeter to exposition of slow neutrons is studied. Different external coatings are used on the dosemeter (polyethylene, alminium, polyethylene + boron, aluminium + boron) and exposure curves (with and without water) are compared. (M.A.C.)

  1. Experimental demonstration of spinor slow light

    Science.gov (United States)

    Lee, Meng-Jung; Ruseckas, Julius; Lee, Chin-Yuan; Kudriašov, Viačeslav; Chang, Kao-Fang; Cho, Hung-Wen; JuzeliÅ«nas, Gediminas; Yu, Ite A.

    2016-03-01

    Over the last decade there has been a continuing interest in slow and stored light based on the electromagnetically induced transparency (EIT) effect, because of their potential applications in quantum information manipulation. However, previous experimental works all dealt with the single-component slow light which cannot be employed as a qubit. In this work, we report the first experimental demonstration of two-component or spinor slow light (SSL) using a double tripod (DT) atom-light coupling scheme. The oscillations between the two components, similar to the Rabi oscillation of a two-level system or a qubit, were observed. Single-photon SSL can be considered as two-color qubits. We experimentally demonstrated a possible application of the DT scheme as quantum memory and quantum rotator for the two-color qubits. This work opens up a new direction in the slow light research.

  2. Experimental demonstration of spinor slow light

    CERN Document Server

    Lee, Meng-Jung; Lee, Chin-Yuan; Kudriasov, Viaceslav; Chang, Kao-Fang; Cho, Hung-Wen; Juzeliunas, Gediminas; Yu, Ite A

    2014-01-01

    Over the last decade the developments of slow, stored and stationary light based on the electromagnetically induced transparency effect have attracted a great deal of attention, stimulated by potential applications such as low-light-level nonlinear optics and quantum information manipulation. The previous experiments all dealt with the single-component slow light. Here we report the first experimental demonstration of two-component or spinor slow light using a double tripod (DT) atom-light coupling scheme which involves two atomic ground state coherences. We observe the neutrino-type oscillations between the two slow light components controlled by the two-photon detuning. We show that the DT scheme for the light storage behaves like the two outcomes of a Mach-Zehnder interferometer enabling high precision measurements of the frequency detuning. Finally, we experimentally demonstrate a possible application of the DT scheme as quantum memory/rotator for the two-color qubits.

  3. Economic Paradigms and Slow American Productivity Growth

    OpenAIRE

    Thurow, Lester C

    1987-01-01

    Conventional explanations of America's slow productivity growth end up by giving up. Much of the slow down remains unexplained by changes in the quality or quantity of conventional inputs. If one looks at changes in occupational employment, it is clear that the productivity problem is an office and not a factory problem. White collar employment has simply grown much faster than it should have grown. To explain this growth, it is necessary to probe into theories of management and why they have...

  4. Blinks slow memory-guided saccades

    OpenAIRE

    Powers, Alice S.; Basso, Michele A.; Evinger, Craig

    2012-01-01

    Memory-guided saccades are slower than visually guided saccades. The usual explanation for this slowing is that the absence of a visual drive reduces the discharge of neurons in the superior colliculus. We tested a related hypothesis: that the slowing of memory-guided saccades was due also to the more frequent occurrence of gaze-evoked blinks with memory-guided saccades compared with visually guided saccades. We recorded gaze-evoked blinks in three monkeys while they performed visually guided...

  5. Frequency response of slow beam extraction process

    International Nuclear Information System (INIS)

    A servo control system has been incorporated into the practical slow extraction system in order to stabilize the spill structure less than a few kHz. Frequency responses of the components of the servo-spill control system and the open-loop frequency response were measured. The beam transfer function of the slow extraction process was derived from the measured data and approximated using a simple function. This is utilized to improve the performance of the servo-loop. (author)

  6. Ultra slow-roll G-inflation

    CERN Document Server

    Hirano, Shin'ichi; Yokoyama, Shuichiro

    2016-01-01

    The conventional slow-roll approximation is broken in the so called "ultra slow-roll" models of inflation, for which the inflaton potential is exactly (or extremely) flat. The interesting nature of (canonical) ultra slow-roll inflation is that the curvature perturbation grows on superhorizon scales, but has a scale-invariant power spectrum. We study the ultra slow-roll inflationary dynamics in the presence of non-canonical kinetic terms of the scalar field, namely ultra slow-roll G-inflation. We compute the evolution of the curvature perturbation and show that the primordial power spectrum follows a broken power law with an oscillation feature. It is demonstrated that this could explain the lack of large-scale power in the cosmic microwave background temperature anisotropies. We also point out that the violation of the null energy condition is prohibited in ultra slow-roll G-inflation and hence a blue tensor tilt is impossible as long as inflation is driven by the potential. This statement is, however, not tr...

  7. Properties of slow oscillation during slow-wave sleep and anesthesia in cats

    OpenAIRE

    Chauvette, Sylvain; Crochet, Sylvain; Volgushev, Maxim; Timofeev, Igor

    2011-01-01

    Deep anesthesia is commonly used as a model of slow-wave sleep (SWS). Ketamine-xylazine anesthesia reproduces the main features of sleep slow oscillation: slow, large amplitude waves in field potential, which are generated by the alternation of hyperpolarized and depolarized states of cortical neurons. However, direct quantitative comparison of field potential and membrane potential fluctuations during natural sleep and anesthesia is lacking, so it remains unclear how well the properties of s...

  8. Host Cell Protein C9orf9 Promotes Viral Proliferation via Interaction with HSV-1 UL25 Protein

    Institute of Scientific and Technical Information of China (English)

    Ying Zhang; Yan-mei Li; Long-ding Liu; Li Jiang; Ma Ji; Rui-ju Jiang; Lei Guo; Yun Liao; Qi-han Li

    2011-01-01

    In light of the scarcity of reports on the interaction between HSV-1 nucleocapsid protein UL25 and its host cell proteins,the purpose of this study is to use yeast two-hybrid screening to search for cellular proteins that can interact with the UL25 protein.C9orf69,a protein of unknown function was identified.The interaction between the two proteins under physiological conditions was also confirmed by biological experiments including co-localization by fluorescence and immunoprecipitation.A preliminary study of the function of C9orf69 showed that it promotes viral proliferation.Further studies showed that C9orf69 did not influence viral multiplication efficiency by transcriptional regulation of viral genes,but indirectly promoted proliferation via interaction with UL25.

  9. Recurrent thrombotic occlusion of a transjugular intrahepatic portosystemic stent-shunt due to activated protein C resistance

    Institute of Scientific and Technical Information of China (English)

    Elmar Siewert; Jan Salzmann; Edmund Purucker; Karl Schürmann; Siegfried Matern

    2005-01-01

    The transjugular intrahepatic portosystemic stent-shunt (TIPS) has successfully been used in the management of refractory variceal bleeding and ascites in patients with portal hypertension. Major drawbacks are the induction of hepatic encephalopathy and shunt dysfunction. We present a 59-year-old woman with alcoholic liver cirrhosis who received a TIPS because of recurrent bleeding from esophageal varices. Stent occlusion occurred 4 mo after placement of the TIPS. Laboratory testing revealed resistance to activated protein C (APC). Combination therapy with low-dose enoxaparin and clopidogrel could not prevent her recurrent stent occlusion. Finally, therapy with high-dose enoxaparin was sufficient to prevent further shunt complications up to now (follow-up period of 1 year). In conclusion, early occlusion of a TIPS warrants testing for thrombophilia. If risk factors are confirmed,anticoagulation should be intensified. There are currently no evidence-based recommendations regarding the best available anticoagulant therapy and surveillance protocol for patients with TIPS.

  10. Functional characterization of the protein C A267T mutation: evidence for impaired secretion due to defective intracellular transport

    Directory of Open Access Journals (Sweden)

    Tjeldhorn Lena

    2010-09-01

    Full Text Available Abstract Background Activated protein C (PC is a serine protease that regulates blood coagulation by inactivating coagulation factors Va and VIIIa. PC deficiency is an autosomally inherited disorder associated with a high risk of recurrent venous thrombosis. The aim of the study was to explore the mechanisms responsible for severe PC deficiency in a patient with the protein C A267T mutation by in-vitro expression studies. Results Huh7 and CHO-K1 cells were transiently transfected with expression vectors containing wild-type (WT PC and mutated PC (A267T PC cDNAs. PC mRNA levels were assessed by qRT-PCR and the PC protein levels were measured by ELISA. The mRNA levels of WT PC and A267T PC were similar, while the intracellular protein level of A267T PC was moderately decreased compared to WT PC. The secretion of A267T PC into the medium was severely impaired. No differences in molecular weights were observed between WT and A267T PC before and after treatment with endo-β-N-acetylglucosaminidase. Proteasomal and lysosomal degradations were examined using lactacystin and bafilomycin, respectively, and revealed that A267T PC was slightly more susceptible for proteasomal degradation than WT PC. Intracellular co-localization analysis indicated that A267T PC was mainly located in the endoplasmic reticulum (ER, whereas WT PC was observed in both ER and Golgi. Conclusions In contrast to what has been reported for other PC mutants, intracellular degradation of A267T PC was not the main/dominant mechanism underlying the reduced intracellular and secretion levels of PC. Our results indicate that the A267T mutation most likely caused misfolding of PC, which might lead to increased retention of the mutated PC in ER.

  11. Human gamma oscillations during slow wave sleep.

    Directory of Open Access Journals (Sweden)

    Mario Valderrama

    Full Text Available Neocortical local field potentials have shown that gamma oscillations occur spontaneously during slow-wave sleep (SWS. At the macroscopic EEG level in the human brain, no evidences were reported so far. In this study, by using simultaneous scalp and intracranial EEG recordings in 20 epileptic subjects, we examined gamma oscillations in cerebral cortex during SWS. We report that gamma oscillations in low (30-50 Hz and high (60-120 Hz frequency bands recurrently emerged in all investigated regions and their amplitudes coincided with specific phases of the cortical slow wave. In most of the cases, multiple oscillatory bursts in different frequency bands from 30 to 120 Hz were correlated with positive peaks of scalp slow waves ("IN-phase" pattern, confirming previous animal findings. In addition, we report another gamma pattern that appears preferentially during the negative phase of the slow wave ("ANTI-phase" pattern. This new pattern presented dominant peaks in the high gamma range and was preferentially expressed in the temporal cortex. Finally, we found that the spatial coherence between cortical sites exhibiting gamma activities was local and fell off quickly when computed between distant sites. Overall, these results provide the first human evidences that gamma oscillations can be observed in macroscopic EEG recordings during sleep. They support the concept that these high-frequency activities might be associated with phasic increases of neural activity during slow oscillations. Such patterned activity in the sleeping brain could play a role in off-line processing of cortical networks.

  12. Magnon Inflation: Slow Roll with Steep Potentials

    CERN Document Server

    Adshead, Peter; Burgess, C P; Hayman, Peter; Patil, Subodh P

    2016-01-01

    We find multi-scalar effective field theories (EFTs) that can achieve a slow inflationary roll despite having a scalar potential that does not satisfy the usual slow-roll condition (d V)^2 << V^2/Mp^2. They evade the usual slow-roll conditions on $V$ because their kinetic energies are dominated by single-derivative terms rather than the usual two-derivative terms. Single derivatives dominate during slow roll and so do not require a breakdown of the usual derivative expansion that underpins calculational control in much of cosmology. The presence of such terms requires some sort of UV Lorentz-symmetry breaking during inflation (besides the usual cosmological breaking). Chromo-natural inflation provides an example of a UV theory that can generate the multi-field single-derivative terms we consider, and we argue that the EFT we find indeed captures the slow-roll conditions for the background evolution for Chromo-natural inflation. We also show that our EFT can be understood as a multi-field generalization ...

  13. Slow phase hemolysis in hypotonic electrolyte solutions.

    Science.gov (United States)

    Chan, T K; LaCelle, P L; Weed, R I

    1975-02-01

    When a population of erythrocytes is partially hemolyzed the time course of hemolysis can be divided into a fast phase and a slow phase. The slow phase occurs with both rapid and gradual addition of the hypotonic medium (rapid and gradual hemolysis). There is no difference in the osmotic fragility of erythrocytes remaining at 60 minutes after rapid or gradual hemolysis. Erythrocytes near their critical hemolytic volume have an equimolar ouabaininsensitive sodium-potassium exchange. Critical non-hemolytic swelling with resulting stress on the membrane appears requisite to slow phase hemolysis since more non-penetrant sucrose is required to prevent slow phase lysis rather than that which would be predicted from the intracellular colloid osmotic pressure due to hemoglobin. Sucrose protection from slow phase hemolysis thus depends not only on counter-balancing the colloid osmotic pressure, but also removal of sufficient intracellular water to prevent critical membrane strain. This model is consistent with that proposed by Katchalsky. Irreversible membrane changes associated with hypotonic stress manifested by persistent stomatocytic shape change and membrane wrinkling on return of cells to isotonicity appear to be due to critical changes in membrane components. Such cells, having normal indices and specific gravity are less deformable than control cells in 2.8 mum pore size polycarbonate filters. PMID:1110261

  14. Slow phase hemolysis in hypotonic electrolyte solutions

    Energy Technology Data Exchange (ETDEWEB)

    Chan, T.K.; LaCelle, P.L.; Weed, R.I.

    1975-02-01

    When a population of erythrocytes is partially hemolyzed the time course of hemolysis can be divided into a fast phase and a slow phase. The slow phase occurs with both rapid and gradual addition of the hypotonic medium (rapid and gradual hemolysis). There is no difference in the osmotic fragility of erythrocytes remaining at 60 minutes after rapid or gradual hemolysis. Erythrocytes near their critical hemolytic volume have an equimolar ouabain-insensitive sodium-potassium exchange. Critical non-hemolytic swelling with resulting stress on the membrane appears requisite to slow phase hemolysis since more non-penetrant sucrose is required to prevent slow phase lysis rather than that which would be predicted from the intracellular colloid osmotic pressure due to hemoglobin. Sucrose protection from slow phase hemolysis thus depends not only on counter-balancing the colloid osmotic pressure, but also removal of sufficient intracellular water to prevent critical membrane strain. This model is consistent with that proposed by Katchalsky. Irreversible membrane changes associated with hypotonic stress manifested by persistent stomatocytic shape change and membrane wrinkling on return of cells to isotonicity appear to be due to critical changes in membrane components. Such cells, having normal indices and specific gravity, are less deformable than control cells in 2.8 ..mu..m pore size polycarbonate filters.

  15. Kinetic slow mode-type solitons

    Directory of Open Access Journals (Sweden)

    K. Baumgärtel

    2005-01-01

    Full Text Available One-dimensional hybrid code simulations are presented, carried out in order both to study solitary waves of the slow mode branch in an isotropic, collisionless, medium-β plasma (βi=0.25 and to test the fluid based soliton interpretation of Cluster observed strong magnetic depressions (Stasiewicz et al., 2003; Stasiewicz, 2004 against kinetic theory. In the simulations, a variety of strongly oblique, large amplitude, solitons are seen, including solitons with Alfvenic polarization, similar to those predicted by the Hall-MHD theory, and robust, almost non-propagating, solitary structures of slow magnetosonic type with strong magnetic field depressions and perpendicular ion heating, which have no counterpart in fluid theory. The results support the soliton-based interpretation of the Cluster observations, but reveal substantial deficiencies of Hall-MHD theory in describing slow mode-type solitons in a plasma of moderate beta.

  16. Slow and fast light switching in ruby

    Science.gov (United States)

    Rajan, Rajitha P.; Riesen, Hans

    2015-05-01

    Studies about light propagation have been undertaken for more than a century. It is now well established that any material that has normal or anomalous dispersion generates slow or fast light. In this paper, we demonstrate an experimental technique to rapidly switch between slow and fast light in ruby. The experiment utilizes transient holeburning to create drastic variation in refractive index of ruby to produce slow as well as fast light. Transient hole-burning involves the depletion of the ground state leading to a highly populated excited state by single frequency laser excitation. This leads to a hole in the absorption spectrum when readout by a laser. We observed a delay of 29 ns and advancement of -11 ns in an external magnetic field of B║c = 12 mT corresponding to a group velocity of c/961 and negative group velocity of -c/365 respectively.

  17. Universality of slow decorrelation in KPZ growth

    CERN Document Server

    Corwin, I; Peche, S

    2010-01-01

    We demonstrate that, under minimal hypothesis, a wide class of growth models diplays a phenomenon known as slow decorrelation, where along certain characteristic directions the range of correlation for fluctuations of the growth surface height is much longer than other directions. We apply this result to certain models known to be in the Kardar-Parisi-Zhang (KPZ) universality class in 1+1 dimension for which the necessary hypothesis holds. These models are the totally asymmetric simple exclusion process (TASEP), last passage percolation (LPP), and the polynuclear growth (PNG) model. Utilizing the slow decorrelation of fluctuations in these models we are able to extend known fluctuation limit process results away from the fixed curves on which they were proved, to general space-time curves. Using the monotonicity of the basic coupling we additionally prove that the partially asymmetric simple exclusion process (PASEP) displays slow decorrelation.

  18. Synchronized ion acceleration by ultraintense slow light

    CERN Document Server

    Brantov, A V; Kovalev, V F; Bychenkov, V Yu

    2015-01-01

    An effective scheme of synchronized laser-triggered ion acceleration and the corresponding theoretical model are proposed for a slow light pulse of relativistic intensity, which penetrates into a near-critical-density plasma, strongly slows, and then increases its group velocity during propagation within a target. The 3D PIC simulations confirm this concept for proton acceleration by a femtosecond petawatt-class laser pulse experiencing relativistic self-focusing, quantify the characteristics of the generated protons, and demonstrate a significant increase of their energy compared with the proton energy generated from optimized ultrathin solid dense foils.

  19. Synchronized Ion Acceleration by Ultraintense Slow Light

    Science.gov (United States)

    Brantov, A. V.; Govras, E. A.; Kovalev, V. F.; Bychenkov, V. Yu.

    2016-02-01

    An effective scheme of synchronized laser-triggered ion acceleration and the corresponding theoretical model are proposed for a slow light pulse of relativistic intensity, which penetrates into a near-critical-density plasma, strongly slows, and then increases its group velocity during propagation within a target. The 3D particle-in-cell simulations confirm this concept for proton acceleration by a femtosecond petawatt-class laser pulse experiencing relativistic self-focusing, quantify the characteristics of the generated protons, and demonstrate a significant increase of their energy compared with the proton energy generated from optimized ultrathin solid dense foils.

  20. Everything looks beautiful in slow motion.

    OpenAIRE

    Sandiland, Nic

    2010-01-01

    A window-based interactive installation set in the context of a shopping centre or high street shopping area. The installation takes a short 10-second video clips of pedestrians as they pass by the front of the window and subsequently replays the video in slow motion and black and white with an accompanying ambient soundtrack. Slow-motion and black and white are standard techniques often employed by the mainstream film industry to emphasise key moments of a narrative in cinema. This work util...

  1. Collision physics with highly stripped slow ions

    International Nuclear Information System (INIS)

    A review about recent studies with highly stripped heavy ions is given. Its scope is limited to mainly inner shell processes and slow collisions compared to the Bohr velocity of electrons in these shells. The processes discussed are: population of excited states by electron capture in asymmetric collision systems; electron capture and excitation in symmetric collisions with an emphasis on the impact parameter dependence of K- to L-shell and K- to K-shell vacancy transfer; the interference structure in the quasimolecular X-rays from slow hydrogen-like ion-atom collisions which is used for direct spectroscopy of quasimolecular energies. (Auth.)

  2. Slow crack growth in spinel in water

    Science.gov (United States)

    Schwantes, S.; Elber, W.

    1983-01-01

    Magnesium aluminate spinel was tested in a water environment at room temperature to establish its slow crack-growth behavior. Ring specimens with artificial flaws on the outside surface were loaded hydraulically on the inside surface. The time to failure was measured. Various precracking techniques were evaluated and multiple precracks were used to minimize the scatter in the static fatigue tests. Statistical analysis techniques were developed to determine the strength and crack velocities for a single flaw. Slow crack-growth rupture was observed at stress intensities as low as 70 percent of K sub c. A strengthening effect was observed in specimens that had survived long-time static fatigue tests.

  3. Critical Slowing Down and Defect Formation

    CERN Document Server

    Pietroni, M

    1999-01-01

    The formation of topological defects in a second order phase transition in the early universe is an out-of-equilibrium process. Condensed matter experiments seem to support Zurek's mechanism, in which the freezing of thermal fluctuations close to the critical point (critical slowing down) plays a crucial role. We discuss how this picture can be extrapolated to the early universe, pointing out that new scaling laws may emerge at very high temperatures and showing how critical slowing down emerges in the context of a relativistic quantum field theory.

  4. Systematic Design of Slow Light Waveguides

    DEFF Research Database (Denmark)

    Wang, Fengwen

    Light can propagate much slower in photonic crystal waveguides and plasmonic waveguides than in vacuum. Slow light propagation in waveguides shows broad prospects in the terabit communication systems. However, it causes severe signal distortions and displays large propagation loss. Moreover it is...

  5. Slow cycling flux pump using digital control

    International Nuclear Information System (INIS)

    A slow cycling flux pump was constructed with digital logic driving a high power operational amplifier for control. Hall sensors allow closed loop control of the secondary currents, allowing switching of the heater driven power cryotrons at the optimum time. Operating efficiency of 87 percent was achieved

  6. A slow gravity compensated atom laser

    DEFF Research Database (Denmark)

    Kleine Büning, G.; Will, J.; Ertmer, W.;

    2010-01-01

    We report on a slow guided atom laser beam outcoupled from a Bose–Einstein condensate of 87Rb atoms in a hybrid trap. The acceleration of the atom laser beam can be controlled by compensating the gravitational acceleration and we reach residual accelerations as low as 0.0027 g. The outcoupling me...

  7. Experimental demonstration of spinor slow light

    Science.gov (United States)

    Lee, Meng-Jung; Ruseckas, Julius; Lee, Chin-Yuan; Kudriašov, Viačeslav; Chang, Kao-Fang; Cho, Hung-Wen; Juzeliānas, Gediminas; Yu, Ite A.

    2014-11-01

    Slow light based on the effect of electromagnetically induced transparency is of great interest due to its applications in low-light-level nonlinear optics and quantum information manipulation. The previous experiments all dealt with the single-component slow light. Here, we report the experimental demonstration of two-component or spinor slow light using a double-tripod atom-light coupling scheme. The scheme involves three atomic ground states coupled to two excited states by six light fields. The oscillation due to the interaction between the two components was observed. On the basis of the stored light, our data showed that the double-tripod scheme behaves like the two outcomes of an interferometer enabling precision measurements of frequency detuning. We experimentally demonstrated a possible application of the double-tripod scheme as quantum memory/rotator for the two-colour qubit. Our study also suggests that the spinor slow light is a better method than a widely used scheme in the nonlinear frequency conversion.

  8. Deficiency of CCAAT/enhancer binding protein family DNA binding prevents malignant conversion of adenoma to carcinoma in NNK-induced lung carcinogenesis in the mouse

    OpenAIRE

    Kimura Shioko; Paiz Jorge; Yoneda Mitsuhiro; Kido Taketomo; Vinson Charles; Ward Jerrold M

    2012-01-01

    Abstract Background The CCAAT/enhancer binding proteins (C/EBPs) play important roles in carcinogenesis of many tumors including the lung. Since multiple C/EBPs are expressed in lung, the combinatorial expression of these C/EBPs on lung carcinogenesis is not known. Methods A transgenic mouse line expressing a dominant negative A-C/EBP under the promoter of lung epithelial Clara cell secretory protein (CCSP) gene in doxycycline dependent fashion was subjected to 4-(methylnitrosamino)-1-(3-pyri...

  9. Properties of slow oscillation during slow-wave sleep and anesthesia in cats.

    Science.gov (United States)

    Chauvette, Sylvain; Crochet, Sylvain; Volgushev, Maxim; Timofeev, Igor

    2011-10-19

    Deep anesthesia is commonly used as a model of slow-wave sleep (SWS). Ketamine-xylazine anesthesia reproduces the main features of sleep slow oscillation: slow, large-amplitude waves in field potential, which are generated by the alternation of hyperpolarized and depolarized states of cortical neurons. However, direct quantitative comparison of field potential and membrane potential fluctuations during natural sleep and anesthesia is lacking, so it remains unclear how well the properties of sleep slow oscillation are reproduced by the ketamine-xylazine anesthesia model. Here, we used field potential and intracellular recordings in different cortical areas in the cat to directly compare properties of slow oscillation during natural sleep and ketamine-xylazine anesthesia. During SWS cortical activity showed higher power in the slow/delta (0.1-4 Hz) and spindle (8-14 Hz) frequency range, whereas under anesthesia the power in the gamma band (30-100 Hz) was higher. During anesthesia, slow waves were more rhythmic and more synchronous across the cortex. Intracellular recordings revealed that silent states were longer and the amplitude of membrane potential around transition between active and silent states was bigger under anesthesia. Slow waves were mostly uniform across cortical areas under anesthesia, but in SWS, they were most pronounced in associative and visual areas but smaller and less regular in somatosensory and motor cortices. We conclude that, although the main features of the slow oscillation in sleep and anesthesia appear similar, multiple cellular and network features are differently expressed during natural SWS compared with ketamine-xylazine anesthesia. PMID:22016533

  10. Binding dynamics of single-stranded DNA binding proteins to fluctuating bubbles in breathing DNA

    International Nuclear Information System (INIS)

    We investigate the dynamics of a single local denaturation zone in a DNA molecule, a so-called DNA bubble, in the presence of single-stranded DNA binding proteins (SSBs). In particular, we develop a dynamical description of the process in terms of a two-dimensional master equation for the time evolution of the probability distribution of having a bubble of size m with n bound SSBs, for the case when m and n are the slowest variables in the system. We derive explicit expressions for the equilibrium statistical weights for a given m and n, which depend on the statistical weight u associated with breaking a base-pair interaction, the loop closure exponent c, the cooperativity parameter σ0, the SSB size λ, and binding strength κ. These statistical weights determine, through the detailed balance condition, the transfer coefficient in the master equation. For the case of slow and fast binding dynamics the problem can be reduced to one-dimensional master equations. In the latter case, we perform explicitly the adiabatic elimination of the fast variable n. Furthermore, we find that for the case that the loop closure is neglected and the binding dynamics is vanishing (but with arbitrary σ0) the eigenvalues and the eigenvectors of the master equation can be obtained analytically, using an orthogonal polynomial approach. We solve the general case numerically (i.e., including SSB binding and the loop closure) as a function of statistical weight u, binding protein size λ, and binding strength κ, and compare to the fast and slow binding limits. In particular, we find that the presence of SSBs in general increases the relaxation time, compared to the case when no binding proteins are present. By tuning the parameters, we can drive the system from regular bubble fluctuation in the absence of SSBs to full denaturation, reflecting experimental and in vivo situations

  11. Slow Tourism and Other Emerging Trends in Finland

    OpenAIRE

    Juvonen, Emmi; Saarnikko, Taru

    2014-01-01

    The subject of the Bachelor’s thesis was to find out the state of slow tourism in Finland today. Slow tourism was created after establishing the Slow Food movement in the 1980’s. The ideology behind Slow tourism lies in slowing down the speed of traveling, choosing more environmentally-friendly transportation methods in the nature of sustainable development, supporting the local produce and local services in the travel destination and getting familiar with the surrounding culture and local pe...

  12. Expression, crystallization and preliminary crystallographic study of mouse hepatitis virus (MHV) nucleocapsid protein C-terminal domain

    International Nuclear Information System (INIS)

    The C-terminal domain of mouse hepatitis virus nucleocapsid protein has been overexpressed in E. coli, purified and crystallized. The crystal belonged to space group P422, with unit-cell parameters a = 66.6, c = 50.8 Å, and diffracted to 2.20 Å resolution. Mouse hepatitis virus (MHV) belongs to the group II coronaviruses. The virus produces nine genes encoding 11 proteins that could be recognized as structural proteins and nonstructural proteins and are crucial for viral RNA synthesis. The nucleocapsid (N) protein, one of the structural proteins, interacts with the 30.4 kb virus genomic RNA to form the helical nucleocapsid and associates with the membrane glycoprotein via its C-terminus to stabilize virion assembly. Here, the expression and crystallization of the MHV nucleocapsid protein C-terminal domain are reported. The crystals diffracted to 2.20 Å resolution and belonged to space group P422, with unit-cell parameters a = 66.6, c = 50.8 Å. Assuming the presence of two molecules in the asymmetric unit, the solvent content is 43.0% (VM = 2.16 Å3 Da−1)

  13. Regulation of endothelial protein C receptor shedding by cytokines is mediated through differential activation of MAP kinase signaling pathways

    International Nuclear Information System (INIS)

    The endothelial protein C receptor (EPCR) plays a pivotal role in coagulation, inflammation, cell proliferation, and cancer, but its activity is markedly changed by ectodomain cleavage and release as the soluble protein (sEPCR). In this study we examined the mechanisms involved in the regulation of EPCR shedding in human umbilical endothelial cells (HUVEC). Interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), but not interferon-γ and interleukin-6, suppressed EPCR mRNA transcription and cell-associated EPCR expression in HUVEC. The release of sEPCR induced by IL-1β and TNF-α correlated with activation of p38 MAPK and c-Jun N-terminal kinase (JNK). EPCR shedding was also induced by phorbol 12-myristate 13-acetate, ionomycin, anisomycin, thiol oxidants or alkylators, thrombin, and disruptors of lipid rafts. Both basal and induced shedding of EPCR was blocked by the metalloproteinase inhibitors, TAPI-0 and GM6001, and by the reduced non-protein thiols, glutathione, dihydrolipoic acid, dithiothreitol, and N-acetyl-L-cysteine. Because other antioxidants and scavengers of reactive oxygen species failed to block the cleavage of EPCR, a direct suppression of metalloproteinase activity seems responsible for the observed effects of reduced thiols. In summary, the shedding of EPCR in HUVEC is effectively regulated by IL-1β and TNF-α, and downstream by MAP kinase signaling pathways and metalloproteinases.

  14. Several Cytokines and Protein C Levels with the Apache II Scoring System for Evaluation of Patients with Sepsis

    Directory of Open Access Journals (Sweden)

    Nurettin Erben

    2012-06-01

    Full Text Available Objective: We investigated whether determination IL-6, IL-8, IL-1beta and TNF-alpha at baseline, total protein C (PC levels at time of admission and 48 hours after initiation could complement the Acute Physiology and Chronic Health Evaluation (APACHE II scoring system to identify patients with sepsis, severe sepsis or septic shock for clinical outcome.Material and Methods: The study was carried out prospectively. 60 consecutive patients with sepsis, severe sepsis or septic shock were included. Blood samples were obtained at baseline and 48 hours after initiation. Cytokines and PC levels in plasma were measured with an enzyme-linked immunoabsorbent assay (ELISA. APACHE II score was calculated on admission.Results: Baseline IL-6 levels and PC levels 48 hours after initiation were predictive of increased mortality (p=0.016, p=0.044 respectively. Baseline IL-6, IL-8 and TNF-alpha baseline levels correlate with the severity of physiologic insult, as determined by the APACHE II score. However, our multiple logistic regression analysis of these did not reveal any predictive value in combination with the APACHE II score.Conclusion: Determination of baseline IL-6 and PC 48 hours after initiation were of predictive value for prognostic evaluation of septic patients, but did not significantly increase predictive power of the APACHE scoring system to identify patients with sepsis for fatal clinical outcome.

  15. GAIP interacting protein C-terminus regulates autophagy and exosome biogenesis of pancreatic cancer through metabolic pathways.

    Directory of Open Access Journals (Sweden)

    Santanu Bhattacharya

    Full Text Available GAIP interacting protein C terminus (GIPC is known to play an important role in a variety of physiological and disease states. In the present study, we have identified a novel role for GIPC as a master regulator of autophagy and the exocytotic pathways in cancer. We show that depletion of GIPC-induced autophagy in pancreatic cancer cells, as evident from the upregulation of the autophagy marker LC3II. We further report that GIPC regulates cellular trafficking pathways by modulating the secretion, biogenesis, and molecular composition of exosomes. We also identified the involvement of GIPC on metabolic stress pathways regulating autophagy and microvesicular shedding, and observed that GIPC status determines the loading of cellular cargo in the exosome. Furthermore, we have shown the overexpression of the drug resistance gene ABCG2 in exosomes from GIPC-depleted pancreatic cancer cells. We also demonstrated that depletion of GIPC from cancer cells sensitized them to gemcitabine treatment, an avenue that can be explored as a potential therapeutic strategy to overcome drug resistance in cancer.

  16. Edwardsiella tarda Outer Membrane Protein C: An Immunogenic Protein Induces Highly Protective Effects in Flounder (Paralichthys olivaceus) against Edwardsiellosis

    Science.gov (United States)

    Liu, Fuguo; Tang, Xiaoqian; Sheng, Xiuzhen; Xing, Jing; Zhan, Wenbin

    2016-01-01

    Outer membrane protein C of Edwardsiella tarda is a major cell surface antigen and it was identified to be an immunogenic protein by Western blot using flounder (Paralichthys olivaceus) anti-recombinant OmpC (rOmpC), and anti-E. tarda antibodies. rOmpC tested the immune protective effect against E. tarda challenge in a flounder model and produced a relative percentage of survival rate of 85%. The immune response of flounder induced by rOmpC was investigated, and the results showed that: (1) the levels of specific serum antibodies induced by rOmpC were significantly higher than the control group after the second week after immunization, and the peak level occurred at week five after immunization; (2) rOmpC could induce the proliferation of sIg+ lymphocytes, and the peak levels of sIg+ lymphocytes in blood, spleen, and pronephros occurred at 4–5 weeks after immunization; and (3) the MHCIIα, CD4-1, IL-1β, IL-6 and TNF-α genes were significantly induced after being injected with rOmpC. Taken together, these results demonstrated that rOmpC could evoke highly protective effects against E. tarda challenge and induce strong innate immune response and humoral immune response of flounder, which indicated that OmpC was a promising vaccine candidate against E. tarda infection. PMID:27420049

  17. 3K3A-activated protein C stimulates postischemic neuronal repair by human neural stem cells in mice

    DEFF Research Database (Denmark)

    Wang, Yaoming; Zhao, Zhen; Rege, Sanket V;

    2016-01-01

    -APC (Lys191-193Ala) mutant in which three Lys residues (KKK191-193) were replaced with alanine, and/or its other mutants with reduced (>90%) anticoagulant activity, engineered to reduce APC-associated bleeding risk while retaining normal cell-signaling activity, have shown benefits in preclinical models...... profile in humans, 3K3A-APC has advanced to clinical trials as a neuroprotectant in ischemic stroke. Recently, 3K3A-APC has been shown to stimulate neuronal production by human neural stem and progenitor cells (NSCs) in vitro via a PAR1-PAR3-sphingosine-1-phosphate-receptor 1-Akt pathway, which suggests......Activated protein C (APC) is a blood protease with anticoagulant activity and cell-signaling activities mediated by the activation of protease-activated receptor 1 (F2R, also known as PAR1) and F2RL1 (also known as PAR3) via noncanonical cleavage. Recombinant variants of APC, such as the 3K3A...

  18. Regulation of endothelial protein C receptor shedding by cytokines is mediated through differential activation of MAP kinase signaling pathways

    Energy Technology Data Exchange (ETDEWEB)

    Menschikowski, Mario, E-mail: Mario.Menschikowski@uniklinikum-dresden.de [Institute of Clinical Chemistry and Laboratory Medicine, Technical University of Dresden, Medical Faculty ' Carl Gustav Carus' , Fetscherstrasse 74, D-01307 Dresden (Germany); Hagelgans, Albert; Eisenhofer, Graeme; Siegert, Gabriele [Institute of Clinical Chemistry and Laboratory Medicine, Technical University of Dresden, Medical Faculty ' Carl Gustav Carus' , Fetscherstrasse 74, D-01307 Dresden (Germany)

    2009-09-10

    The endothelial protein C receptor (EPCR) plays a pivotal role in coagulation, inflammation, cell proliferation, and cancer, but its activity is markedly changed by ectodomain cleavage and release as the soluble protein (sEPCR). In this study we examined the mechanisms involved in the regulation of EPCR shedding in human umbilical endothelial cells (HUVEC). Interleukin-1{beta} (IL-1{beta}) and tumor necrosis factor-{alpha} (TNF-{alpha}), but not interferon-{gamma} and interleukin-6, suppressed EPCR mRNA transcription and cell-associated EPCR expression in HUVEC. The release of sEPCR induced by IL-1{beta} and TNF-{alpha} correlated with activation of p38 MAPK and c-Jun N-terminal kinase (JNK). EPCR shedding was also induced by phorbol 12-myristate 13-acetate, ionomycin, anisomycin, thiol oxidants or alkylators, thrombin, and disruptors of lipid rafts. Both basal and induced shedding of EPCR was blocked by the metalloproteinase inhibitors, TAPI-0 and GM6001, and by the reduced non-protein thiols, glutathione, dihydrolipoic acid, dithiothreitol, and N-acetyl-L-cysteine. Because other antioxidants and scavengers of reactive oxygen species failed to block the cleavage of EPCR, a direct suppression of metalloproteinase activity seems responsible for the observed effects of reduced thiols. In summary, the shedding of EPCR in HUVEC is effectively regulated by IL-1{beta} and TNF-{alpha}, and downstream by MAP kinase signaling pathways and metalloproteinases.

  19. Thrombin inhibits HMGB1-mediated proinflammatory signaling responses when endothelial protein C receptor is occupied by its natural ligand

    Directory of Open Access Journals (Sweden)

    Jong-Sup Bae

    2013-11-01

    Full Text Available High mobility group box 1 (HMGB1 is involved in thepathogenesis of vascular diseases. Unlike activated protein C(APC, the activation of PAR-1 by thrombin is known to elicitproinflammatory responses. To determine whether the occupancyof EPCR by the Gla-domain of APC is responsible for thePAR-1-dependent antiinflammatory activity of the protease, wepretreated HUVECs with the PC zymogen and then activatedPAR-1 with thrombin. It was found that thrombin downregulatesthe HMGB1-mediated induction of both TNF-α andIL-6 and inhibits the activation of both p38 MAPK and NF-κB inHUVECs pretreated with PC. Furthermore, thrombin inhibitedHMGB1-mediated hyperpermeability and leukocyte adhesion/migration by inhibiting the expression of cell adhesion moleculesin HUVECs if EPCR was occupied. Collectively, theseresults suggest the concept that thrombin can initiate proinflammatoryresponses in vascular endothelial cells through theactivation of PAR-1 may not hold true for normal vesselsexpressing EPCR under in vivo conditions. [BMB Reports 2013;46(11: 544-549

  20. Circulating microparticles and the risk of thrombosis in inherited deficiencies of antithrombin, protein C and protein S.

    Science.gov (United States)

    Campello, Elena; Spiezia, Luca; Radu, Claudia M; Bulato, Cristiana; Gavasso, Sabrina; Tormene, Daniela; Woodhams, Barry; Dalla Valle, Fabio; Simioni, Paolo

    2016-01-01

    Many subjects carrying inherited thrombophilic defects will never experience venous thromboembolism (VTE) while other individuals developed recurrent VTE with no known additional risk factors. High levels of circulating microparticles (MP) have been associated with increased risk of VTE in patients with factor V Leiden and prothrombin G20210A mutation, suggesting a possible contribution of MP in the hypercoagulability of mild genetic thrombophilia. The role of MP as additional risk factor of VTE in carriers of natural clotting inhibitors defects (severe thrombophilia) has never been assessed. Plasma levels of annexin V-MP, endothelial-derived MP (EMP), platelet-derived MP (PMP), tissue factor-bearing MP (TF+) and the MP procoagulant activity (PPL) were measured in 132 carriers of natural anticoagulant deficiencies (25 antithrombin, 63 protein C and 64 protein S defect) and in 132 age and gender-matched healthy controls. Carriers of natural anticoagulant deficiencies, overall and separately considered, presented with higher median levels of annexin V-MP, EMP, PMP, TF+MP and PPL activity than healthy controls (pEMP and PMP had an adjusted OR for VTE of 3.36 (95% CI, 1.59 to 7.11), 9.26 (95% CI, 3.55 to 24.1) and 2.72 (95%CI, 1.16 to 6.38), respectively. Elevated levels of circulating MP can play a role in carriers of mild and severe inherited thrombophilia. The clinical implications of this association remain to be defined. PMID:26354831

  1. Slow and fast light in semiconductors

    Science.gov (United States)

    Sedgwick, Forrest Grant

    Slow and fast light are the propagation of optical signals at group velocities below and above the speed of light in a given medium. There has been great interest in the use of nonlinear optics to engineer slow and fast light dispersion for applications in optical communications and radio-frequency or microwave photonics. Early results in this field were primarily confined to dilute atomic systems. While these results were impressive, they had two major barriers to practical application. First, the wavelengths were not compatible with fiber optic telecommunications. More importantly, the bandwidth obtainable in these experiments was inherently low; 100 kHz or less. Within the last five years slow and fast light effects have been observed and engineered in a much wider variety of systems. In this work, we detail our efforts to realize slow and fast light in semiconductor systems. There are three primary advantages of semiconductor systems: fiber-compatible wavelengths, larger bandwidth, and simplification of integration with other optical components. In this work we will explore three different types of physical mechanisms for implementing slow and fast light. The first is electromagnetically induced transparency (EIT). In transporting this process to semiconductors, we initially turn our attention to quantum dots or "artificial atoms". We present simulations of a quantum dot EIT-based device within the context of an optical communications link and we derive results which are generally applicable to a broad class of slow light devices. We then present experimental results realizing EIT in quantum wells by using long-lived electron spin coherence. The second mechanism we will explore is coherent population oscillations (CPO), also known as carrier density pulsations (CDP). We examine for the first time how both slow and fast light may be achieved in a quantum well semiconductor optical amplifier (SOA) while operating in the gain regime. Again, we simulate the device

  2. The Slow Learner in Mathematics: Characteristics and Needs of the Slow Learner

    Science.gov (United States)

    Schulz, Richard W.

    1973-01-01

    Strengths and weaknesses of students classified as slow learners'' are presented with emphasis on affective concerns. The teacher, as strategic change-agent, is given suggestions for managing instruction. (LS)

  3. Critical slowing down in a dynamic duopoly

    Science.gov (United States)

    Escobido, M. G. O.; Hatano, N.

    2015-01-01

    Anticipating critical transitions is very important in economic systems as it can mean survival or demise of firms under stressful competition. As such identifying indicators that can provide early warning to these transitions are very crucial. In other complex systems, critical slowing down has been shown to anticipate critical transitions. In this paper, we investigate the applicability of the concept in the heterogeneous quantity competition between two firms. We develop a dynamic model where the duopoly can adjust their production in a logistic process. We show that the resulting dynamics is formally equivalent to a competitive Lotka-Volterra system. We investigate the behavior of the dominant eigenvalues and identify conditions that critical slowing down can provide early warning to the critical transitions in the dynamic duopoly.

  4. A tilted transversely isotropic slowness surface approximation

    KAUST Repository

    Stovas, A.

    2012-05-09

    The relation between vertical and horizontal slownesses, better known as the dispersion relation, for transversely isotropic media with a tilted symmetry axis (TTI) requires solving a quartic polynomial equation, which does not admit a practical explicit solution to be used, for example, in downward continuation. Using a combination of the perturbation theory with respect to the anelliptic parameter and Shanks transform to improve the accuracy of the expansion, we develop an explicit formula for the vertical slowness that is highly accurate for all practical purposes. It also reveals some insights into the anisotropy parameter dependency of the dispersion relation including the low impact that the anelliptic parameter has on the vertical placement of reflectors for a small tilt in the symmetry angle. © 2012 European Association of Geoscientists & Engineers.

  5. Slowing progression of chronic kidney disease.

    Science.gov (United States)

    Drawz, Paul E; Rosenberg, Mark E

    2013-12-01

    Early identification of chronic kidney disease (CKD) provides an opportunity to implement therapies to improve kidney function and slow progression. The goal of this article is to review established and developing clinical therapies directed at slowing progression. The importance of controlling blood pressure will be discussed along with the target blood pressure that should be achieved in CKD patients. Therapy directed at inhibiting the renin-angiotensin-aldosterone system remains the mainstay of treatment with single-agent inhibition of this system being as good as dual blockade with fewer adverse effects. Other therapies that may be used include correction of metabolic acidosis, dietary protein restriction, and new models for delivering care to patients with CKD. Emerging therapies targeting endothelin, uric acid, kidney fibrosis, and oxidant stress hold promise for the future. PMID:25019022

  6. Slow and fast light in semiconductor waveguides

    DEFF Research Database (Denmark)

    Mørk, Jesper; Hansen, Per Lunnemann; Xue, Weiqi;

    2010-01-01

    Investigations of slow and fast light effects in semiconductor waveguides entail interesting physics and point to a number of promising applications. In this review we give an overview of recent progress in the field, in particular focusing on the physical mechanisms of electromagnetically induced...... transparency and coherent population oscillations. While electromagnetically induced transparency has been the most important effect in realizing slowdown effects in atomic gasses, progress has been comparatively slow in semiconductors due to inherent problems of fast dephasing times and inhomogeneous...... broadening in quantum dots. The physics of electromagnetically induced transparency in semiconductors is discussed, emphasizing these limitations and recent suggestions for overcoming them. On the other hand, the mechanism of coherent population oscillations relies on wave mixing effects and is well suited...

  7. Slow microwaves in left-handed materials

    Science.gov (United States)

    di Gennaro, E.; Parimi, P. V.; Lu, W. T.; Sridhar, S.; Derov, J. S.; Turchinetz, B.

    2005-07-01

    Remarkably slow propagation of microwaves in two different classes of left-handed materials (LHM’s) is reported from microwave-pulse and continuous-wave transmission measurements. Microwave dispersion in a composite LHM made of split-ring resonators and wire strips reveals group velocity vg˜c/50 , where c is the free-space light velocity. Photonic crystals (PhC’s) made of dielectric Al2O3 rods reveal vg˜c/10 . Group delay dispersion of both the composite LHM and PhC’s determined from the experiment is in complete agreement with that obtained from theory. The slow group velocities are quantitatively described by the strong dispersion observed in these materials.

  8. Slow scrambling in disordered quantum systems

    CERN Document Server

    Swingle, Brian

    2016-01-01

    Recent work has studied the growth of commutators as a probe of chaos and information scrambling in quantum many-body systems. In this work we study the effect of static disorder on the growth of commutators in a variety of contexts. We find generically that disorder slows the onset of scrambling, and, in the case of a many-body localized state, partially halts it. We access the many-body localized state using a standard fixed point Hamiltonian, and we show that operators exhibit slow logarithmic growth under time evolution. We compare the result with the expected growth of commutators in both localized and delocalized non-interacting disordered models. Finally, based on a scaling argument, we state a conjecture about the effect of weak interactions on the growth of commutators in an interacting diffusive metal.

  9. Polymeric membrane studied using slow positron beam

    International Nuclear Information System (INIS)

    A radioisotope slow positron beam has been built at the Chung Yuan Christian University in Taiwan for the research and development in membrane science and technology. Doppler broadening energy spectra and positron annihilation lifetime have been measured as a function of positron energy up to 30 keV in a polyamide membrane prepared by the interfacial polymerization between triethylenetetraamine (TETA) and trimesoyl chloride (TMC) on modified porous polyacrylonitrile (PAN) asymmetric membrane. The multilayer structures and free-volume depth profile for this asymmetric membrane system are obtained. Positron annihilation spectroscopy coupled with a slow beam could provide new information about size selectivity of transporting molecules and guidance for molecular designs in polymeric membranes

  10. Ionization of atoms by slow heavy particles

    CERN Document Server

    Roberts, B M; Gribakin, G F

    2016-01-01

    Atoms and molecules can become ionized during the scattering of a slow, heavy particle off a bound electron. Such an interaction involving leptophilic weakly interacting massive particles (WIMPs) is a promising possible explanation for the anomalous 9 sigma annual modulation in the DAMA dark matter direct detection experiment [R. Bernabei et al., Eur. Phys. J. C 73, 2648 (2013)]. We demonstrate the applicability of the Born approximation for such an interaction by showing its equivalence to the semiclassical adiabatic treatment of atomic ionization by slow-moving WIMPs. Conventional wisdom has it that the ionization probability for such a process should be exponentially small. We show, however, that due to nonanalytic, cusp-like behaviour of Coulomb functions close to the nucleus this suppression is removed, leading to an effective atomic structure enhancement. We also show that electron relativistic effects actually give the dominant contribution to such a process, meaning that nonrelativistic calculations m...

  11. Periodic orbits near a bifurcating slow manifold

    DEFF Research Database (Denmark)

    Kristiansen, Kristian Uldall

    2015-01-01

    This paper studies a class of $1\\frac12$-degree-of-freedom Hamiltonian systems with a slowly varying phase that unfolds a Hamiltonian pitchfork bifurcation. The main result of the paper is that there exists an order of $\\ln^2\\epsilon^{-1}$-many periodic orbits that all stay within an $\\mathcal O......(\\epsilon^{1/3})$-distance from the union of the normally elliptic slow manifolds that occur as a result of the bifurcation. Here $\\epsilon\\ll 1$ measures the time scale separation. These periodic orbits are predominantly unstable. The proof is based on averaging of two blowup systems, allowing one to estimate...... the effect of the singularity, combined with results on asymptotics of the second Painleve equation. The stable orbits of smallest amplitude that are {persistently} obtained by these methods remain slightly further away from the slow manifold being distant by an order $\\mathcal O(\\epsilon^{1/3}\\ln^{1...

  12. Slow Turism, Hangö stad

    OpenAIRE

    Salo, Annika Ingeborg

    2011-01-01

    Syftet med detta arbete var att utreda vad Hangö stad har för möjligheter att nå slow stadens kriterier. Därtill kartläggs vilka faktorer redan kan identifieras. Delsyftet är att få fram företagarnas intresse att gå enligt denna ideologi. Examensarbetet avgränsas till att behandla områden som berör turismen. Problemställningen, hur kan Hangö stad uppnå de kriterier som behövs för att få benämningen Slow – stad. Och det krävs mycket av de beslutfattande organen i Hangö samt av företagarna och ...

  13. Capping complex formation at the slow-growing end of the actin filament.

    Science.gov (United States)

    Kostyukova, A S

    2008-12-01

    Actin filaments are polar; their barbed (fast-growing) and pointed (slow-growing) ends differ in structure and dynamic properties. The slow-growing end is regulated by tropomodulins, a family of capping proteins that require tropomyosins for optimal function. There are four tropomodulin isoforms; their distributions vary depending on tissue type and change during development. The C-terminal half of tropomodulin contains one compact domain represented by alternating alpha-helices and beta-structures. The tropomyosin-independent actin-capping site is located at the C-terminus. The N-terminal half has no regular structure; however, it contains a tropomyosin-dependent actin-capping site and two tropomyosin-binding sites. One tropomodulin molecule can bind two tropomyosin molecules. Effectiveness of tropomodulin binding to tropomyosin depends on the tropomyosin isoform. Regulation of tropomodulin binding at the pointed end as well as capping effectiveness in the presence of specific tropomyosins may affect formation of local cytoskeleton and dynamics of actin filaments in cells. PMID:19216712

  14. Effects of dermatan sulfate derivatives on platelet surface P-selectin expression and protein C activity in blood of inflammatory bowel disease patients

    OpenAIRE

    Ji, Sheng-Li; Du, Hai-Yan; Chi, Yan-Qing; Cui, Hui-Fei; Cao, Ji-Chao; Geng, Mei-yu; Guan, Hua-Shi

    2004-01-01

    AIM: To investigate the effect of dermatan sulfate (DS) derivatives on platelet surface P-selectin expression and blood activated protein C (APC) activity in patients with inflammatory bowel disease (IBD), and to clarity the anti-inflammatory mechanism of DS derivatives.

  15. Ly6/uPAR-related protein C4.4A as a marker of solid growth pattern and poor prognosis in lung adenocarcinoma

    DEFF Research Database (Denmark)

    Jacobsen, Benedikte; Muley, Thomas; Meister, Michael;

    2013-01-01

    We have recently shown that the protein C4.4A is induced in early precursor lesions of pulmonary adenocarcinomas and squamous cell carcinomas. In the present study, we aimed at analyzing the impact of C4.4A on the survival of non-small cell lung cancer patients and determining whether its...

  16. Human Gamma Oscillations during Slow Wave Sleep

    OpenAIRE

    Mario Valderrama; Benoît Crépon; Vicente Botella-Soler; Jacques Martinerie; Dominique Hasboun; Catalina Alvarado-Rojas; Michel Baulac; Claude Adam; Vincent Navarro; Michel Le Van Quyen

    2012-01-01

    Neocortical local field potentials have shown that gamma oscillations occur spontaneously during slow-wave sleep (SWS). At the macroscopic EEG level in the human brain, no evidences were reported so far. In this study, by using simultaneous scalp and intracranial EEG recordings in 20 epileptic subjects, we examined gamma oscillations in cerebral cortex during SWS. We report that gamma oscillations in low (30-50 Hz) and high (60-120 Hz) frequency bands recurrently emerged in all investigated r...

  17. Slow crack growth in polycarbonate films

    OpenAIRE

    Cortet, Pierre-Philippe; Santucci, Stéphane; Vanel, Loïc; Ciliberto, Sergio

    2005-01-01

    We study experimentally the slow growth of a single crack in polycarbonate films submitted to uniaxial and constant imposed stress. The specificity of fracture in polycarbonate films is the appearance of flame shaped macroscopic process zones at the tips of the crack. Supported by an experimental study of the mechanical properties of polycarbonate films, an analysis of the stress dependence of the mean ratio between the process zone and crack lengths, during the crack growth, show a quantitat...

  18. Probing Strongly Coupled Chameleons with Slow Neutrons

    OpenAIRE

    Brax, Philippe; Pignol, Guillaume; Roulier, Damien

    2013-01-01

    We consider different methods to probe chameleons with slow neutrons. Chameleon modify the potential of bouncing neutrons over a flat mirror in the terrestrial gravitational field. This induces a shift in the energy levels of the neutrons which could be detected in current experiments like GRANIT. Chameleons between parallel plates have a field profile which is bubble-like and which would modify the phase of neutrons in interferometric experiments. We show that this new method of detection is...

  19. Slow light fiber systems in microwave photonics

    OpenAIRE

    Thevenaz L.; Chin S.-H.; Berger P.; Bourderionnet J.; Sales S.; Sancho-Dura J.

    2011-01-01

    Slow light systems are particularly attractive for analog signal processing, since their inherent limitation to a delay-bandwidth product of 1 is less critical for analog systems such as those used in microwave photonics. We present here the implementation of two basic functions - phase shifting and true time delaying - fully optically controlled using stimulated Brillouin scattering in optical fibers. The combination of these two functions makes possible the implementation of true time delay...

  20. Examination of Graphene with Very Slow Electrons

    Czech Academy of Sciences Publication Activity Database

    Mikmeková, Eliška; Frank, Luděk

    Ostrava: TANGER, 2014. ISBN 978-80-87294-55-0. [NANOCON 2014. International Conference /6./. Brno (CZ), 05.11.2014-07.11.2014] R&D Projects: GA TA ČR TE01020118; GA MŠk(CZ) LO1212 Institutional support: RVO:68081731 Keywords : graphene * slow electrons * very low energy scanning electron microscopy * ultralow energy STEM Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering

  1. Slowed demand ushers in summer season

    International Nuclear Information System (INIS)

    This article is the June 1996 market summary in uranium market. During this reporting period, there were six deals in the U3O8 spot market and three long-term deals for U3O8. There were four deals for UF6 conversion, and the spot market for uranium separation services had no transactions. This was little change from the previous month's activities, and this slowness was reflected in the price trends of little or no increase

  2. Textile slow release systems with medical applications

    OpenAIRE

    Breteler, ten, M.R.; Nierstrasz, V.A.; Warmoeskerken, M.M.C.G.

    2002-01-01

    In the development of medical drug delivery systems, attention has been increasingly focused on slow- or controlled delivery systems in order to achieve an optimal therapeutic effect. Since the administration of drugs often requires a defined or minimum effective dosage in the human body, more conventional delivery systems such as tablets require relatively high doses, which can result in undesired toxic effects. Subsequent degradation of the drug in the human body will result in a drug conce...

  3. New slow-releasing molybdenum fertilizer.

    Science.gov (United States)

    Bandyopadhyay, Siladitya; Bhattacharya, Ishita; Ghosh, Kunal; Varadachari, Chandrika

    2008-02-27

    This paper describes a new water-insoluble molybdenum compound that has been developed as a slow-release fertilizer. The compound is an inorganic polymer formed by inclusion of molybdenum within a long-chain polyphosphate structure. It was designed by a process of "reverse engineering" of the molecule. Synthesis involved reaction of phosphoric acid with magnesium oxide, molybdenum trioxide, and sodium carbonate at 275 degrees C. Kinetics of reaction revealed complex multistage processes. X-ray diffraction patterns showed a crystalline nature with short-range as well as long-range ordering. The magnesium sodium polymolybdophosphate had ideal slow-release characteristics; it had low water solubility and high citrate solubility and was powdery, free flowing, and nonhygroscopic. Field testing showed an 80% increase in yield of green gram at a low dose of 0.04 kg/ha Mo. Nodulation increased by over 161%, and N content of gram increased by 20%. The slow-release fertilizer would provide an effective, low-cost, and environmentaly friendly alternative to Mo fertilization. PMID:18247562

  4. Slow movement execution in event-related potentials (P300).

    Science.gov (United States)

    Naruse, Kumi; Sakuma, Haruo; Hirai, Takane

    2002-02-01

    We examined whether slow movement execution has an effect on cognitive and information processing by measuring the P300 component. 8 subjects performed a continuous slow forearm rotational movement using 2 task speeds. Slow (a 30-50% decrease from the subject's Preferred speed) and Very Slow (a 60-80% decrease). The mean coefficient of variation for rotation speed under Very Slow was higher than that under Slow, showing that the subjects found it difficult to perform the Very Slow task smoothly. The EEG score of alpha-1 (8-10 Hz) under Slow Condition was increased significantly more than under the Preferred Condition; however, the increase under Very Slow was small when compared with Preferred. After performing the task. P300 latency under Very Slow increased significantly as compared to that at pretask. Further, P300 amplitude decreased tinder both speed conditions when compared to that at pretask, and a significant decrease was seen under the Slow Condition at Fz, whereas the decrease under the Very Slow Condition was small. These differences indicated that a more complicated neural composition and an increase in subjects' attention might have been involved when the task was performed under the Very Slow Condition. We concluded that slow movement execution may have an influence on cognitive function and may depend on the percentage of decrease from the Preferred speed of the individual. PMID:11883570

  5. Binding of calcium and carbonate to polyacrylates.

    Science.gov (United States)

    Tribello, Gareth A; Liew, CheeChin; Parrinello, Michele

    2009-05-21

    Polyacrylate molecules can be used to slow the growth of calcium carbonate. However, little is known about the mechanism by which the molecules impede the growth rate. A recent computational study (Bulo et al. Macromolecules 2007, 40, 3437) used metadynamics to investigate the binding of calcium to polyacrylate chains and has thrown some light on the coiling and precipitation of these polymers. We extend these simulations to examine the binding of calcium and carbonate to polyacrylate chains. We show that calcium complexed with both carbonate and polyacrylate is a very stable species. The free energies of calcium-carbonate-polyacrylate complexes, with different polymer configurations, are calculated, and differences in the free energy of the binding of carbonate are shown to be due to differences in the amount of steric hindrance about the calcium, which prevents the approach of the carbonate ion. PMID:19400592

  6. Levels of soluble endothelial protein C receptor are associated with CD4+ changes in Maraviroc-treated HIV-infected patients.

    Directory of Open Access Journals (Sweden)

    Silvia Nozza

    Full Text Available BACKGROUND: Inflammation is a key feature of HIV infection and is correlated with long-term negative cardiovascular outcomes. Therapy-induced increases in CD4(+ cell counts can control inflammation, as shown by decreases of coagulation and inflammation markers during efficacious therapy. Maraviroc, a CCR5-antagonist, has resulted in larger increases in CD4(+ counts both in naïve and experienced subjects compared to traditional antiretroviral therapy. OBJECTIVES AND METHODS: To examine if a member of the protein C anticoagulant and anti-inflammatory pathway, and marker of coagulation and inflammation, the soluble endothelial protein C receptor, is modified by infection and therapy-related variables in patients treated with Maraviroc. Endothelial protein C receptor, together with other established markers of inflammation and coagulation (CRP, IL-6, D-dimer and soluble thrombomodulin was studied in 43 patients on traditional antiretroviral therapy and in 45 on Maraviroc during 48 weeks of follow-up. RESULTS: Soluble endothelial protein C receptor was the only marker that could discriminate at least partially between patients with a good response to Maraviroc and patients who did not respond with an adequate increase in CD4(+ cell counts (more than 500 cells/µL by week 48. CONCLUSIONS: Elevated levels of soluble endothelial protein C receptor, a sensitive marker of endothelial damage, indicated a low level of inflammation and coagulation activation in Maraviroc treated patients not picked up by other widely used markers. Persistent elevated levels of this marker at 48 weeks from beginning of treatment with Maraviroc were related to a poor increase in CD4(+ cells.

  7. Purifying selection drives the evolution of surfactant protein C (SP-C) independently of body temperature regulation in mammals.

    Science.gov (United States)

    Potter, Sally; Orgeig, Sandra; Donnellan, Stephen; Daniels, Christopher B

    2007-06-01

    The pulmonary surfactant system of heterothermic mammals must be capable of dealing with the effect of low body temperatures on the physical state of the lipid components. We have shown previously that there is a modest increase in surfactant cholesterol during periods of torpor, however these changes do not fully explain the capacity of surfactant to function under the wide range of physical conditions imposed by torpor. Here we examine indirectly the role of surfactant protein C (SP-C) in adapting to variable body temperatures by testing for the presence of positive (adaptive) selection during evolutionary transitions between heterothermy and homeothermy. We sequenced SP-C from genomic DNA of 32 mammalian species from groups of closely related heterothermic and homeothermic species (contrasts). We used phylogenetic analysis by maximum likelihood estimates of rates of non-synonymous to synonymous substitutions and fully Bayesian inference of these sequences to determine whether the mode of body temperature regulation exerts a selection pressure driving the molecular adaptation of SP-C. The protein sequence of SP-C is highly conserved with synonymous or highly conservative amino acid substitutions being predominant. The evolution of SP-C among mammals is characterised by high codon usage bias and high rates of transition/transversion. The only contrast to show evidence of positive selection was that of the bears (Ursus americanus and U. maritimus). The significance of this result is unclear. We show that SP-C is under strong evolutionary constraints, driven by purifying selection, presumably to maintain protein function despite variation in the mode of body temperature regulation. PMID:20483290

  8. The readiness potential reflects intentional binding

    Directory of Open Access Journals (Sweden)

    Han-Gue eJo

    2014-06-01

    Full Text Available When a voluntary action is causally linked with a sensory outcome, the action and its consequent effect are perceived as being closer together in time. This effect is called intentional binding. Although many experiments were conducted on this phenomenon, the underlying neural mechanisms are not well understood. While intentional binding is specific to voluntary action, we presumed that preconscious brain activity (the readiness potential, RP, which occurs before an action is made, might play an important role in this binding effect. In this study, the brain dynamics were recorded with electroencephalography (EEG and analyzed in single-trials in order to estimate whether intentional binding is correlated with the early neural processes. Moreover, we were interested in different behavioral performance between meditators and non-meditators since meditators are expected to be able to keep attention more consistently on a task. Thus, we performed the intentional binding paradigm with twenty mindfulness meditators and compared them to matched controls. Although, we did not observe a group effect on either behavioral data or EEG recordings, we found that self-initiated movements following ongoing negative deflections of slow cortical potentials (SCPs result in a stronger binding effect compared to positive potentials, especially regarding the perceived time of the consequent effect. Our results provide the first direct evidence that the early neural activity within the range of SCPs affects perceived time of a sensory outcome that is caused by intentional action.

  9. The readiness potential reflects intentional binding

    Science.gov (United States)

    Jo, Han-Gue; Wittmann, Marc; Hinterberger, Thilo; Schmidt, Stefan

    2014-01-01

    When a voluntary action is causally linked with a sensory outcome, the action and its consequent effect are perceived as being closer together in time. This effect is called intentional binding. Although many experiments were conducted on this phenomenon, the underlying neural mechanisms are not well understood. While intentional binding is specific to voluntary action, we presumed that preconscious brain activity (the readiness potential, RP), which occurs before an action is made, might play an important role in this binding effect. In this study, the brain dynamics were recorded with electroencephalography (EEG) and analyzed in single-trials in order to estimate whether intentional binding is correlated with the early neural processes. Moreover, we were interested in different behavioral performance between meditators and non-meditators since meditators are expected to be able to keep attention more consistently on a task. Thus, we performed the intentional binding paradigm with 20 mindfulness meditators and compared them to matched controls. Although, we did not observe a group effect on either behavioral data or EEG recordings, we found that self-initiated movements following ongoing negative deflections of slow cortical potentials (SCPs) result in a stronger binding effect compared to positive potentials, especially regarding the perceived time of the consequent effect. Our results provide the first direct evidence that the early neural activity within the range of SCPs affects perceived time of a sensory outcome that is caused by intentional action. PMID:24959135

  10. Binding of peptides to HLA-DQ molecules: peptide binding properties of the disease-associated HLA-DQ(alpha 1*0501, beta 1*0201) molecule

    DEFF Research Database (Denmark)

    Johansen, B H; Buus, S; Vartdal, F;

    1994-01-01

    assay. The MB 65 kDa 243-255Y peptide bound to DQ2 in a strictly pH-dependent fashion, with optimal binding around pH 5 and only weak binding at pH 7.4. The association of the MB 65 kDa 243-255Y peptide to DQ2 was slow, but once formed, the peptide-HLA complexes were very stable. The binding of peptides...

  11. Human pentraxin 3 binds to the complement regulator c4b-binding protein.

    Directory of Open Access Journals (Sweden)

    Anne Braunschweig

    Full Text Available The long pentraxin 3 (PTX3 is a soluble recognition molecule with multiple functions including innate immune defense against certain microbes and the clearance of apoptotic cells. PTX3 interacts with recognition molecules of the classical and lectin complement pathways and thus initiates complement activation. In addition, binding of PTX3 to the alternative complement pathway regulator factor H was shown. Here, we show that PTX3 binds to the classical and lectin pathway regulator C4b-binding protein (C4BP. A PTX3-binding site was identified within short consensus repeats 1-3 of the C4BP α-chain. PTX3 did not interfere with the cofactor activity of C4BP in the fluid phase and C4BP maintained its complement regulatory activity when bound to PTX3 on surfaces. While C4BP and factor H did not compete for PTX3 binding, the interaction of C4BP with PTX3 was inhibited by C1q and by L-ficolin. PTX3 bound to human fibroblast- and endothelial cell-derived extracellular matrices and recruited functionally active C4BP to these surfaces. Whereas PTX3 enhanced the activation of the classical/lectin pathway and caused enhanced C3 deposition on extracellular matrix, deposition of terminal pathway components and the generation of the inflammatory mediator C5a were not increased. Furthermore, PTX3 enhanced the binding of C4BP to late apoptotic cells, which resulted in an increased rate of inactivation of cell surface bound C4b and a reduction in the deposition of C5b-9. Thus, in addition to complement activators, PTX3 interacts with complement inhibitors including C4BP. This balanced interaction on extracellular matrix and on apoptotic cells may prevent excessive local complement activation that would otherwise lead to inflammation and host tissue damage.

  12. Neutron Slowing-Down Time and Thermalization Time Constant in Graphite

    International Nuclear Information System (INIS)

    The classical mechanics are able to describe the energy decrease of fast neutrons in their collision with moderator nuclei. However, when those neutrons are slowed down into the energy range of chemical binding of the moderator, such a simple model in which the collision of neutrons is treated as that of billiard balls is not valid; therefore more extended models have been suggested, including phonon exchange between the neutron and moderator lattice. In order to prove their validity, a series of pulsed neutron experiments was performed to investigate neutron moderation and thermalization in a graphite pile. The graphite pile is of nuclear reactor grade with density 1.54 and is 240 cm in height and 120 cm in a side of its hexagonal cross-section. Bursts of neutrons of width 1 microsecond were generated at the centre of the pile. The slowing-down and diffusing neutrons were detected by bare and energy-selective, filter-covered BF3 counters and analysed with a 256-channel time analyser. By interpreting that the increment of the difference of the events between the bare and the filter covered counter is due to the contribution made by that fraction of the neutrons slowing down at the time of measurement below the cut-off energy of the filter, slowing-down times in graphite were determined. As the results of the experiment, slowing-down times below 1.46, 0.61, 0.50, 0.41 and 0.21 eV were determined as 23, 36.9, 41.6, 45.8 and 87.5 μs respectively. The thermalization time constant in graphite was also determined as (296 ± 50)μs by using the silver filter transmission method. It is concluded that the crystal model is capable of describing most satisfactorily the slowing-down and thermalization phenomena in graphite. (author)

  13. Cyclic AMP (cAMP) Receptor Protein-cAMP Complex Regulates Heparosan Production in Escherichia coli Strain Nissle 1917.

    Science.gov (United States)

    Yan, Huihui; Bao, Feifei; Zhao, Liping; Yu, Yanying; Tang, Jiaqin; Zhou, Xianxuan

    2015-11-01

    Heparosan serves as the starting carbon backbone for the chemoenzymatic synthesis of heparin, a widely used clinical anticoagulant drug. The availability of heparosan is a significant concern for the cost-effective synthesis of bioengineered heparin. The carbon source is known as the pivotal factor affecting heparosan production. However, the mechanism by which carbon sources control the biosynthesis of heparosan is unclear. In this study, we found that the biosynthesis of heparosan was influenced by different carbon sources. Glucose inhibits the biosynthesis of heparosan, while the addition of either fructose or mannose increases the yield of heparosan. Further study demonstrated that the cyclic AMP (cAMP)-cAMP receptor protein (CRP) complex binds to the upstream region of the region 3 promoter and stimulates the transcription of the gene cluster for heparosan biosynthesis. Site-directed mutagenesis of the CRP binding site abolished its capability of binding CRP and eliminated the stimulative effect on transcription. (1)H nuclear magnetic resonance (NMR) analysis was further performed to determine the Escherichia coli strain Nissle 1917 (EcN) heparosan structure and quantify extracellular heparosan production. Our results add to the understanding of the regulation of heparosan biosynthesis and may contribute to the study of other exopolysaccharide-producing strains. PMID:26319872

  14. Slow Wave Sleep and Long Duration Spaceflight

    Science.gov (United States)

    Whitmire, Alexandra; Orr, Martin; Arias, Diana; Rueger, Melanie; Johnston, Smith; Leveton, Lauren

    2012-01-01

    While ground research has clearly shown that preserving adequate quantities of sleep is essential for optimal health and performance, changes in the progression, order and /or duration of specific stages of sleep is also associated with deleterious outcomes. As seen in Figure 1, in healthy individuals, REM and Non-REM sleep alternate cyclically, with stages of Non-REM sleep structured chronologically. In the early parts of the night, for instance, Non-REM stages 3 and 4 (Slow Wave Sleep, or SWS) last longer while REM sleep spans shorter; as night progresses, the length of SWS is reduced as REM sleep lengthens. This process allows for SWS to establish precedence , with increases in SWS seen when recovering from sleep deprivation. SWS is indeed regarded as the most restorative portion of sleep. During SWS, physiological activities such as hormone secretion, muscle recovery, and immune responses are underway, while neurological processes required for long term learning and memory consolidation, also occur. The structure and duration of specific sleep stages may vary independent of total sleep duration, and changes in the structure and duration have been shown to be associated with deleterious outcomes. Individuals with narcolepsy enter sleep through REM as opposed to stage 1 of NREM. Disrupting slow wave sleep for several consecutive nights without reducing total sleep duration or sleep efficiency is associated with decreased pain threshold, increased discomfort, fatigue, and the inflammatory flare response in skin. Depression has been shown to be associated with a reduction of slow wave sleep and increased REM sleep. Given research that shows deleterious outcomes are associated with changes in sleep structure, it is essential to characterize and mitigate not only total sleep duration, but also changes in sleep stages.

  15. Slow-plasmon resonant nano-strip antennas

    DEFF Research Database (Denmark)

    Søndergaard, Thomas; Beermann, Jonas; Boltasseva, Alexandra;

    2008-01-01

    Resonant scattering by gold nanostrip antennas due to constructive interference of counterpropagating slow surface plasmon polaritons SPPs is analyzed, including the quasistatic limit of ultrasmall antennas, and experimentally demonstrated. The phase of slow SPP reflection by strip ends is found ...

  16. Slow-plasmon resonant-nanostrip antennas: Analysis and demonstration

    DEFF Research Database (Denmark)

    Søndergaard, Thomas; Beermann, J.; Boltasseva, Alexandra; Bozhevolnyi, S.I.

    2008-01-01

    Resonant scattering by gold nanostrip antennas due to constructive interference of counterpropagating slow surface plasmon polaritons (SPPs) is analyzed, including the quasistatic limit of ultrasmall antennas, and experimentally demonstrated. The phase of slow SPP reflection by strip ends is found...

  17. Sustainable Development of Slow Fashion Businesses: Customer Value Approach

    Directory of Open Access Journals (Sweden)

    Sojin Jung

    2016-06-01

    Full Text Available As an alternative to the prevalent fast fashion model, slow fashion has emerged as a way of enhancing sustainability in the fashion industry, yet how slow fashion can enhance profitability is still largely unknown. Based on a customer value creation framework, this study empirically tested a structural model that specified the slow fashion attributes that contribute to creating perceived customer value, which subsequently increases a consumer’s intention to buy and pay a price premium for slow fashion products. An analysis of 221 U.S. consumer data revealed that delivering exclusive product value is significantly critical in creating customer value for slow fashion, and customer value, in turn, positively affects consumers’ purchase intentions. Further analysis also revealed that different slow fashion attributes distinctively affect customer value. This provides potential strategies on which slow fashion businesses can focus to secure an economically sustainable business model, thereby continuously improving environmental and social sustainability with the slow fashion ideal.

  18. Involvement of cytokines in slow wave sleep

    OpenAIRE

    Krueger, James M.; Clinton, James M.; Winters, Bradley D.; Zielinski, Mark R.; Taishi, Ping; Jewett, Kathryn A.; Davis, Christopher J.

    2011-01-01

    Cytokines such as tumor necrosis factor alpha (TNFα) and interleukin-1 beta (IL1β) play a role in sleep regulation in health and disease. TNFα or IL1β injection enhances non-rapid eye movement sleep. Inhibition of TNFα or IL1β reduces spontaneous sleep. Mice lacking TNFα or IL1β receptors sleep less. In normal humans and in multiple disease states, plasma levels of TNFα covary with EEG slow wave activity (SWA) and sleep propensity. Many of the symptoms induced by sleep loss, for example, slee...

  19. Slow crack growth in polycarbonate films

    CERN Document Server

    Cortet, Pierre-Philippe; Vanel, Loic; Ciliberto, Sergio

    2005-01-01

    We study experimentally the slow growth of a single crack in polycarbonate films submitted to uniaxial and constant imposed stress. The specificity of fracture in polycarbonate films is the appearance of flame shaped macroscopic process zones at the tips of the crack. Supported by an experimental study of the mechanical properties of polycarbonate films, an analysis of the stress dependence of the mean ratio between the process zone and crack lengths, during the crack growth, show a quantitative agreement with the Dugdale-Barenblatt model of the plastic process zone. We find that the fracture growth curves obey strong scaling properties that lead to a well defined growth master curve.

  20. Atom slowing via dispersive optical interactions

    Science.gov (United States)

    Hamamda, M.; Boustimi, M.; Correia, F.; Baudon, J.; Taillandier-Loize, T.; Dutier, G.; Perales, F.; Ducloy, M.

    2012-02-01

    A promising technique of atom slowing is proposed. It is based upon the dispersive interaction of atoms with optical potential pulses generated by a far-off-resonance standing wave modulated in time. Each pulse reduces the velocity by a small amount. By repeating the process thousands of times, the velocity can be lowered from several hundreds of meters per second down to almost zero, over a path as short as 20cm. In the absence of any random recoil process, the initial characteristics of the beam are preserved.

  1. Slow relaxation in structure-forming ferrofluids.

    Science.gov (United States)

    Sreekumari, Aparna; Ilg, Patrick

    2013-10-01

    We study the behavior of colloidal magnetic fluids at low density for various dipolar interaction strengths by performing extensive Langevin dynamics simulations with model parameters that mimic cobalt-based ferrofluids used in experiments. Our study mainly focuses on the structural and dynamical properties of dipolar fluids and the influence of structural changes on their dynamics. Drastic changes from chainlike to networklike structures in the absence of an external magnetic field are observed. This crossover plays an important role in the slowing down of dynamics that is reflected in various dynamical properties including the tracer diffusion and the viscosity and also in the structural relaxation. PMID:24229180

  2. Moving Crystal Slow-Neutron Wavelength Analyser

    DEFF Research Database (Denmark)

    Buras, B.; Kjems, Jørgen

    1973-01-01

    Experimental proof that a moving single crystal can serve as a slow-neutron wavelength analyser of special features is presented. When the crystal moves with a velocity h/(2 md) (h-Planck constant, m-neutron mass, d-interplanar spacing) perpendicular to the diffracting plane and the analysed...... neutron beam is parallel to the diffracting plane, then neutrons of different wave-lengths contained in the incident beam are simultaneously diffracted under different reflection angles and recorded by a position-sensitive detector. Special features of this analysing system are briefly discussed....

  3. Formation of 11-trans slow reacting substances.

    OpenAIRE

    Atrache, V; Sok, D E; Pai, J K; Sih, C J

    1981-01-01

    Under strongly basic conditions [excess LiOH, dimethoxyethane/water (4:1, vol/vol)], purified slow reacting substances (SRSs) SRS-GSH and SRS-Cys were not isomerized to their corresponding 11-trans isomers. However, addition of thiols such as glutathione (GSH) or L-cysteine to this basic medium produced various amounts of 11-trans-SRS, depending on the thiol concentration. This chemical isomerization was inhibited by the radical scavenger 4-hydroxy-2,2,6,6-tetramethylpiperidinooxy free radica...

  4. Void Formation and Roughening in Slow Fracture

    OpenAIRE

    Afek, Itai; Bouchbinder, Eran; Katzav, Eytan; Mathiesen, Joachim; Procaccia, Itamar

    2004-01-01

    Slow crack propagation in ductile, and in certain brittle materials, appears to take place via the nucleation of voids ahead of the crack tip due to plastic yields, followed by the coalescence of these voids. Post mortem analysis of the resulting fracture surfaces of ductile and brittle materials on the $\\mu$m-mm and the nm scales respectively, reveals self-affine cracks with anomalous scaling exponent $\\zeta\\approx 0.8$ in 3-dimensions and $\\zeta\\approx 0.65$ in 2-dimensions. In this paper w...

  5. Scattering of Slow Neutrons by Gaseous Methane

    International Nuclear Information System (INIS)

    Slow neutron scattering by molecular gases is discussed. The most detailed comparison between theoretical and experimental results has been on gaseous methane which shows conclusively that the quantum nature of the rotational levels must be explicitly taken into account to obtain agreement with the experimental results. It is also shown theoretically that interference scattering, that is interference scattering between two distinct atoms of the molecule, has an effect which can be observed. This effect has been observed experimentally in methane and apparently also for propane. It is pointed out that the theory makes quite definite predictions at smaller momentum transfers than has been measured. Thus experiments at smaller momentum transfers are needed. (author)

  6. Principles of Slow Fashion Application in Clothing Collection Creation

    OpenAIRE

    Agnė Antanavičiūtė; Vaida Dobilaitė

    2015-01-01

    Today we can clearly see the damage which is caused by fast fashion production and mass consumption. Therefore, a relevant issue is how to reduce consumption, waste, and threat to the environment and human health. Research into the slow fashion designers approach towards eco-friendly and slow fashion products shows that it is necessary to spread ideas of slow fashion widely and teach users about ecologically friendly clothing. Therefore, this paper analyses theoretical and practical slow fash...

  7. Nonlinear Gain Saturation in Active Slow Light Photonic Crystal Waveguides

    DEFF Research Database (Denmark)

    Chen, Yaohui; Mørk, Jesper

    2013-01-01

    We present a quantitative three-dimensional analysis of slow-light enhanced traveling wave amplification in an active semiconductor photonic crystal waveguides. The impact of slow-light propagation on the nonlinear gain saturation of the device is investigated.......We present a quantitative three-dimensional analysis of slow-light enhanced traveling wave amplification in an active semiconductor photonic crystal waveguides. The impact of slow-light propagation on the nonlinear gain saturation of the device is investigated....

  8. Triggering sleep slow waves by transcranial magnetic stimulation

    OpenAIRE

    Massimini, Marcello; Ferrarelli, Fabio; Esser, Steve K.; Riedner, Brady A.; Huber, Reto; Murphy, Michael; Peterson, Michael J.; Tononi, Giulio

    2007-01-01

    During much of sleep, cortical neurons undergo near-synchronous slow oscillation cycles in membrane potential, which give rise to the largest spontaneous waves observed in the normal electroencephalogram (EEG). Slow oscillations underlie characteristic features of the sleep EEG, such as slow waves and spindles. Here we show that, in sleeping subjects, slow waves and spindles can be triggered noninvasively and reliably by transcranial magnetic stimulation (TMS). With appropriate stimulation pa...

  9. Slow-light effects in photonic crystal membrane lasers

    DEFF Research Database (Denmark)

    Xue, Weiqi; Yu, Yi; Ottaviano, Luisa;

    2015-01-01

    In this paper, we present a systematic investigation of photonic crystal cavity laser operating in the slow-light regime. The dependence of lasing threshold on the effect of slow-light will be particularly highlighted.......In this paper, we present a systematic investigation of photonic crystal cavity laser operating in the slow-light regime. The dependence of lasing threshold on the effect of slow-light will be particularly highlighted....

  10. Molecular cloning and expression analysis of rainbow trout (Oncorhynchus mykiss)CCAAT/enhancer binding protein genes and their responses to induction by GH in vitro and in vivo

    Science.gov (United States)

    CCAAT/enhancer-binding proteins (C/EBPs) are transcription factors consisting of six isoforms and play diverse physiological roles in vertebrates. In rainbow trout (Oncorhynchus mykiss), in addition to the reported C/EBPbeta1,we have isolated cDNA of four other isoforms, C/EBPalpha, C/EBPbeta2, C/E...

  11. Structural Conservation Despite Huge Sequence Diversity Allows EPCR Binding by the PfEMP1 Family Implicated in Severe Childhood Malaria

    DEFF Research Database (Denmark)

    Lau, Clinton K.Y.; Turner, Louise; Jespersen, Jakob S.;

    2015-01-01

    The PfEMP1 family of surface proteins is central for Plasmodium falciparum virulence and must retain the ability to bind to host receptors while also diversifying to aid immune evasion. The interaction between CIDRa1 domains of PfEMP1 and endothelial protein C receptor (EPCR) is associated with...

  12. The surfactant protein C mutation A116D alters cellular processing, stress tolerance, surfactant lipid composition, and immune cell activation

    Directory of Open Access Journals (Sweden)

    Zarbock Ralf

    2012-03-01

    Full Text Available Abstract Background Surfactant protein C (SP-C is important for the function of pulmonary surfactant. Heterozygous mutations in SFTPC, the gene encoding SP-C, cause sporadic and familial interstitial lung disease (ILD in children and adults. Mutations mapping to the BRICHOS domain located within the SP-C proprotein result in perinuclear aggregation of the proprotein. In this study, we investigated the effects of the mutation A116D in the BRICHOS domain of SP-C on cellular homeostasis. We also evaluated the ability of drugs currently used in ILD therapy to counteract these effects. Methods SP-CA116D was expressed in MLE-12 alveolar epithelial cells. We assessed in vitro the consequences for cellular homeostasis, immune response and effects of azathioprine, hydroxychloroquine, methylprednisolone and cyclophosphamide. Results Stable expression of SP-CA116D in MLE-12 alveolar epithelial cells resulted in increased intracellular accumulation of proSP-C processing intermediates. SP-CA116D expression further led to reduced cell viability and increased levels of the chaperones Hsp90, Hsp70, calreticulin and calnexin. Lipid analysis revealed decreased intracellular levels of phosphatidylcholine (PC and increased lyso-PC levels. Treatment with methylprednisolone or hydroxychloroquine partially restored these lipid alterations. Furthermore, SP-CA116D cells secreted soluble factors into the medium that modulated surface expression of CCR2 or CXCR1 receptors on CD4+ lymphocytes and neutrophils, suggesting a direct paracrine effect of SP-CA116D on neighboring cells in the alveolar space. Conclusions We show that the A116D mutation leads to impaired processing of proSP-C in alveolar epithelial cells, alters cell viability and lipid composition, and also activates cells of the immune system. In addition, we show that some of the effects of the mutation on cellular homeostasis can be antagonized by application of pharmaceuticals commonly applied in ILD therapy

  13. Cermet with Slow TiC Coarsening During Sintering

    Science.gov (United States)

    Lin, Chun-Ming; Tsai, Che-Wei; Huang, Sheng-Min; Yang, Chih-Chao; Yeh, Jien-Wei

    2014-10-01

    New TiC/Co1.5CrFeNi1.5Ti0.5 cermet was developed by exploiting the advantages of the high-entropy alloy (HEA) binder. A much finer grain structure and thus improved hardness-toughness combination were obtained as compared with two traditional binders, Ni and Ni13Mo7. From the coarsening behavior of TiC grains, the coarsening process of TiC in these three binders is diffusion-controlled. The activation energy of TiC + 20%Co1.5CrFeNi1.5Ti0.5 is the highest and that of TiC + 20%Ni is the lowest. The high activation energy of the Co1.5CrFeNi1.5Ti0.5 binder was attributable to its high content of carbon-strong-binding elements, Cr and Ti, and cooperative diffusion and higher packing density of multiple different-sized atoms. Low diffusion coefficient, low surface energy of TiC grains, and low solubility of Ti in the HEA liquid explain the slow coarsening of TiC grains. This study demonstrates that Co1.5CrFeNi1.5Ti0.5 is an excellent HEA binder for TiC cermets.

  14. Good, Clean, Fair: The Rhetoric of the Slow Food Movement

    Science.gov (United States)

    Schneider, Stephen

    2008-01-01

    This article outlines the origins of the Slow Food movement before examining the ways in which Slow Food rhetoric seeks to redefine gastronomy and combat the more deleterious effects of globalization. In articulating a new gastronomy, Slow Food founder Carlo Petrini attempts to reconstruct the gastronomy of Jean Anthelme Brillat-Savarin, at once…

  15. Maxwell Equations for Slow-Moving Media

    Science.gov (United States)

    Rozov, Andrey

    2015-12-01

    In the present work, the Minkowski equations obtained on the basis of theory of relativity are used to describe electromagnetic fields in moving media. But important electromagnetic processes run under non-relativistic conditions of slow-moving media. Therefore, one should carry out its description in terms of classical mechanics. Hertz derived electrodynamic equations for moving media within the frame of classical mechanics on the basis of the Maxwell theory. His equations disagree with the experimental data concerned with the moving dielectrics. In the paper, a way of description of electromagnetic fields in slow-moving media on the basis of the Maxwell theory within the frame of classical mechanics is offered by combining the Hertz approach and the experimental data concerned with the movement of dielectrics in electromagnetic fields. Received Maxwell equations lack asymmetry in the description of the reciprocal electrodynamic action of a magnet and a conductor and conform to known experimental data. Comparative analysis of the Minkowski and Maxwell models is carried out.

  16. Colectomy for idiopathic slow transit constipation

    Institute of Scientific and Technical Information of China (English)

    童卫东; 刘宝华; 张胜本; 张连阳; 黄显凯

    2003-01-01

    Objective: To evaluate the intervention of colectomy on a group of patients with idiopathic slow transit constipation (STC).Methods: Thirty-four patients with STC, underwent colectomy during recent 10 years in our department, were subjected and followed for a mean length of 34 months, and their colon transits, defecograms, colonoscopic examination, sex hormone detection, and immunohistochemical studies were retrospectively reviewed.Results: The colonic transit time ranged from 96 to 240 h, with a mean time of 136 h.Eighty-five percent of patients (29/34) accompanied with outlet obstructed constipation, and 50% (17/34) showed abnormal sex hormone levels.Colectomy obtained satisfactory results in most patients, except one case of recurrence.Moreover, more neurons positive to nitric oxide synthase (NOS) and lesser to vasoactive intestinal polypeptide (VIP) were seen in the colonic myenteric plexus.Conclusion: Colectomy produces a satisfactory functional outcome in the majority of patients undergoing surgery for slow transit constipation, but accompanied pelvic dysfunction must be corrected simultaneously.

  17. Slow Solar Wind: Observations and Modeling

    Science.gov (United States)

    Abbo, L.; Ofman, L.; Antiochos, S. K.; Hansteen, V. H.; Harra, L.; Ko, Y.-K.; Lapenta, G.; Li, B.; Riley, P.; Strachan, L.; von Steiger, R.; Wang, Y.-M.

    2016-06-01

    While it is certain that the fast solar wind originates from coronal holes, where and how the slow solar wind (SSW) is formed remains an outstanding question in solar physics even in the post-SOHO era. The quest for the SSW origin forms a major objective for the planned future missions such as the Solar Orbiter and Solar Probe Plus. Nonetheless, results from spacecraft data, combined with theoretical modeling, have helped to investigate many aspects of the SSW. Fundamental physical properties of the coronal plasma have been derived from spectroscopic and imaging remote-sensing data and in situ data, and these results have provided crucial insights for a deeper understanding of the origin and acceleration of the SSW. Advanced models of the SSW in coronal streamers and other structures have been developed using 3D MHD and multi-fluid equations. However, the following questions remain open: What are the source regions and their contributions to the SSW? What is the role of the magnetic topology in the corona for the origin, acceleration and energy deposition of the SSW? What are the possible acceleration and heating mechanisms for the SSW? The aim of this review is to present insights on the SSW origin and formation gathered from the discussions at the International Space Science Institute (ISSI) by the Team entitled "Slow solar wind sources and acceleration mechanisms in the corona" held in Bern (Switzerland) in March 2014 and 2015.

  18. Binding Isotherms and Time Courses Readily from Magnetic Resonance.

    Science.gov (United States)

    Xu, Jia; Van Doren, Steven R

    2016-08-16

    Evidence is presented that binding isotherms, simple or biphasic, can be extracted directly from noninterpreted, complex 2D NMR spectra using principal component analysis (PCA) to reveal the largest trend(s) across the series. This approach renders peak picking unnecessary for tracking population changes. In 1:1 binding, the first principal component captures the binding isotherm from NMR-detected titrations in fast, slow, and even intermediate and mixed exchange regimes, as illustrated for phospholigand associations with proteins. Although the sigmoidal shifts and line broadening of intermediate exchange distorts binding isotherms constructed conventionally, applying PCA directly to these spectra along with Pareto scaling overcomes the distortion. Applying PCA to time-domain NMR data also yields binding isotherms from titrations in fast or slow exchange. The algorithm readily extracts from magnetic resonance imaging movie time courses such as breathing and heart rate in chest imaging. Similarly, two-step binding processes detected by NMR are easily captured by principal components 1 and 2. PCA obviates the customary focus on specific peaks or regions of images. Applying it directly to a series of complex data will easily delineate binding isotherms, equilibrium shifts, and time courses of reactions or fluctuations. PMID:27458657

  19. Factors Contributing Decreased Performance Of Slow Learners

    Directory of Open Access Journals (Sweden)

    Dr. L. Kannan

    2015-03-01

    Full Text Available Back ground Even experienced teaching faculty and administrators can be challenged by learners who have not able to perform up to expected need in their annual performance of their students these students are called as slow learnersStruggle learners. There should be a designed study to foster discussion about diagnosing particular problems that contribute with meeting objectives of slow learners. Methodology The study was performed on the entire current first year of Medical students were all the three internal assessments of 250 students performance is taken in to consideration for the study. This study is of cross section type.After obtaining the list of all students marks in internal examination from medical education unit supporting mentors are contacted to meet the students and confidentiality is maintained throughout the study. After obtaining informed consent a questionnaire was administered to the students by the investigator. The questionnaire contains the following sections. Section I will be on the background characteristics of the student name age sex type of family. Section II will be on the details of their learning capabilities. Section III will focus on the awareness of the slow learners in which the precipitating factors contributing to them. Results The prevalence of slow learners as low achievers were contributed to be 32.4 percentages.The performance of the students is based on combination of all three internal assessment marks including theory and practical performance. In this the students age ranges from 17 to 21 years the mean age of student was contributed to be 17.81 and majority of the students were in the age group of 18 years which contributed to be 16867.2.In the present study majority were males 13252.8 compared to females 11847.2.but when study is compared to percentage of attendance majority of the individual 15177 scored more than 50 percentage of marks have more than 80 percentage of attendance but when

  20. Binding of complement regulators factor H and C4b binding protein to group A streptococcal strains isolated from tonsillar tissue and blood.

    Science.gov (United States)

    Suvilehto, Jari; Jarva, Hanna; Seppänen, Mikko; Siljander, Tuula; Vuopio-Varkila, Jaana; Meri, Seppo

    2008-06-01

    Group A streptococcus (GAS) is the most common pathogen causing bacterial pharyngitis. We isolated streptococcal strains from tonsils removed from patients with tonsillar disease (n=202) and studied their ability to bind the complement regulators factor H (FH) and C4b binding protein (C4BP) using 125 I-labeled proteins. Blood isolates of GAS (n=10) were obtained from patients with bacteraemia. Streptococci were isolated from 21% of the tonsillitis patients. The emm and T types of the GAS strains were determined. Of the 26 GAS strains studied, only six could bind FH and/or C4BP above the threshold levels. The fraction of the offered radioactive protein bound ranged between 6-12% for FH and 19-56% for C4BP. The clinical course of the tonsillar disease was not related to the binding of FH or C4BP by GAS. The binding strains were mostly of the T4M4 or T28M28 type. From the invasive strains (n=10), three bound FH (binding level: 8-11%) and two C4BP (36-39%). The binding correlated only partially to M-protein (emm) type suggesting that the binding was not exclusively due to M-protein. The results indicate that complement regulator binding by GAS is only partially related to pathogenicity and not a universal property of all group A streptococci. PMID:18538613

  1. Strongly coupled slow-light polaritons in one-dimensional disordered localized states

    CERN Document Server

    Gao, Jie; Liang, Baolai; Schmitteckert, Peter; Lehoucq, Gaelle; Xavier, Stephane; Xu, Xinan; Busch, Kurt; Huffaker, Diana L; De Rossi, Alfredo; Wong, Chee Wei

    2013-01-01

    Cavity quantum electrodynamics advances the coherent control of a single quantum emitter with a quantized radiation field mode, typically piecewise engineered for the highest finesse and confinement in the cavity field. This enables the possibility of strong coupling for chip-scale quantum processing, but till now is limited to few research groups that can achieve the precision and deterministic requirements for these polariton states. Here we observe for the first time coherent polariton states of strong coupled single quantum dot excitons in inherently disordered one-dimensional localized modes in slow-light photonic crystals. Large vacuum Rabi splittings up to 311 {\\mu}eV are observed, one of the largest avoided crossings in the solid-state. Our tight-binding models with quantum impurities detail these strong localized polaritons, spanning different disorder strengths, complementary to model-extracted pure dephasing and incoherent pumping rates. Such disorder-induced slow-light polaritons provide a platfor...

  2. Development of Methods for Measuring Protein C Inhibitor and Antithrombin: Use of Monoclonal Antibodies against the Reactive Center Loop-Inserted Forms of the Serpins

    OpenAIRE

    Kjellberg, Margareta

    2007-01-01

    Protein C inhibitor (PCI) and antithrombin (AT) are serine protease inhibitors (serpins) that are involved in the regulation of coagulation. Like other inhibitory serpins, PCI and AT adopt different structural conformations that are related to their functions. The cleaved, inactive form is a result of cleavage by a protease, and the latent form, which is also inactive, can arise due to a mutation in the serpin. Methods that quantify the different forms can be useful as diagnostic tools. The a...

  3. Detailed Mechanisms of the Inactivation of Factor VIIIa by Activated Protein C in the Presence of Its Cofactors, Protein S and Factor V*

    OpenAIRE

    Gale, Andrew J.; Cramer, Thomas J.; Rozenshteyn, Diana; Cruz, Jason R.

    2008-01-01

    Factor VIIIa is inactivated by a combination of two mechanisms. Activation of factor VIII by thrombin results in a heterotrimeric factor VIIIa that spontaneously inactivates due to dissociation of the A2 subunit. Additionally, factor VIIIa is cleaved by the anticoagulant serine protease, activated protein C, at two cleavage sites, Arg336 in the A1 subunit and Arg562 in the A2 subunit. We previously characterized an engineered variant of factor VIII which contains a dis...

  4. Total iron binding capacity

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003489.htm Total iron binding capacity To use the sharing features on this page, please enable JavaScript. Total iron binding capacity (TIBC) is a blood test to ...

  5. Threshold Characteristics of Slow-Light Photonic Crystal Lasers

    Science.gov (United States)

    Xue, Weiqi; Yu, Yi; Ottaviano, Luisa; Chen, Yaohui; Semenova, Elizaveta; Yvind, Kresten; Mork, Jesper

    2016-02-01

    The threshold properties of photonic crystal quantum dot lasers operating in the slow-light regime are investigated experimentally and theoretically. Measurements show that, in contrast to conventional lasers, the threshold gain attains a minimum value for a specific cavity length. The experimental results are explained by an analytical theory for the laser threshold that takes into account the effects of slow light and random disorder due to unavoidable fabrication imperfections. Longer lasers are found to operate deeper into the slow-light region, leading to a trade-off between slow-light induced reduction of the mirror loss and slow-light enhancement of disorder-induced losses.

  6. Threshold Characteristics of Slow-Light Photonic Crystal Lasers

    CERN Document Server

    Xue, Weiqi; Ottaviano, Luisa; Chen, Yaohui; Semenova, Elizaveta; Yvind, Kresten; Mork, Jesper

    2015-01-01

    The threshold properties of photonic crystal quantum dot lasers operating in the slow-light regime are investigated experimentally and theoretically. Measurements show that, in contrast to conventional lasers, the threshold gain attains a minimum value for a specific cavity length. The experimental results are explained by an analytical theory for the laser threshold that takes into account the effects of slow-light and random disorder due to unavoidable fabrication imperfections. Longer lasers are found to operate deeper into the slow-light region, leading to a trade-off between slow-light induced reduction of the mirror loss and slow-light enhancement of disorder-induced losses.

  7. Electrophysiological and biochemical studies of slow responses to serotonin and dopamine of snail identified neurons. Mediating role of the cyclic AMP

    International Nuclear Information System (INIS)

    In this research thesis, the electrophysiological study of slow incoming currents induced in some identified neurons of the Helix aspersa snail by serotonin and dopamine shows that they are associated with a decrease of a potassium conductance involved in the modulation of the action potential duration. By means of enzymatic tests performed on a single cell, and of electrophysiological experiments, the author shows that the cyclic AMP is an intracellular mediator involved in the genesis of these slow responses. Moreover, the obtained results show that serotonin and dopamine act by binding to specific receptors, and that these receptors activate the adenylate-cyclase through a GTP binding protein

  8. Expressions of beta-catenin, APC Protein, C-myc and Cyclin D1 in Ovarian Epithelial Tumor and Their Implication

    Institute of Scientific and Technical Information of China (English)

    LIN Xiao; LI Yu; MI Can

    2007-01-01

    Objective: To investigate the expressions of beta-catenin, protein APC (adenomatous polyposis coli protein), c-myc and cyclin D1 and their implication in ovarian epithelial tumor. Methods: Immunohistochemical staining with SP method was conducted to identify the expressions of beta-catenin, APC protein, c-myc and cyclin D1 in ovarian epithelial tumor in 48 cases. Results: The abnormal expression rate of beta-catenin in malignant and borderline ovarian epithelial tumors was higher than that in benign epithelial tumors (P<0.01). The expression rates of c-myc and cyclin-D1 in ovarian malignant and borderline epithelial tumors were higher than those in benign epithelial tumors too(P<0.05). The prevalence of APC protein positive expression in benign epithelial tumors were significantly greater than that in malignant epithelial tumors (P<0.05). A significant negative correlation was found between beta-catenin and APC protein in ovarian epithelial tumors; while a significant positive correlation was found between beta-catenin, c-myc and cyclin-D1 in ovarian epithelial tumor (P<0.05). Conclusion: The abnormal expressions of Beta-catenin, APC protein, c-myc and cyclin-D1 might be used to indicate the malignance transform of ovarian epithelial tumors.

  9. Plant Hormone Binding Sites

    OpenAIRE

    Napier, Richard

    2004-01-01

    • Aims Receptors for plant hormones are becoming identified with increasing rapidity, although a frustrating number remain unknown. There have also been many more hormone‐binding proteins described than receptors. This Botanical Briefing summarizes what has been discovered about hormone binding sites, their discovery and descriptions, and will not dwell on receptor functions or activities except where these are relevant to understand binding.

  10. Strong DNA deformation required for extremely slow DNA threading intercalation by a binuclear ruthenium complex

    Science.gov (United States)

    Almaqwashi, Ali A.; Paramanathan, Thayaparan; Lincoln, Per; Rouzina, Ioulia; Westerlund, Fredrik; Williams, Mark C.

    2014-01-01

    DNA intercalation by threading is expected to yield high affinity and slow dissociation, properties desirable for DNA-targeted therapeutics. To measure these properties, we utilize single molecule DNA stretching to quantify both the binding affinity and the force-dependent threading intercalation kinetics of the binuclear ruthenium complex Δ,Δ-[μ‐bidppz‐(phen)4Ru2]4+ (Δ,Δ-P). We measure the DNA elongation at a range of constant stretching forces using optical tweezers, allowing direct characterization of the intercalation kinetics as well as the amount intercalated at equilibrium. Higher forces exponentially facilitate the intercalative binding, leading to a profound decrease in the binding site size that results in one ligand intercalated at almost every DNA base stack. The zero force Δ,Δ-P intercalation Kd is 44 nM, 25-fold stronger than the analogous mono-nuclear ligand (Δ-P). The force-dependent kinetics analysis reveals a mechanism that requires DNA elongation of 0.33 nm for association, relaxation to an equilibrium elongation of 0.19 nm, and an additional elongation of 0.14 nm from the equilibrium state for dissociation. In cells, a molecule with binding properties similar to Δ,Δ-P may rapidly bind DNA destabilized by enzymes during replication or transcription, but upon enzyme dissociation it is predicted to remain intercalated for several hours, thereby interfering with essential biological processes. PMID:25245944

  11. Slow neutron scattering by water molecules

    International Nuclear Information System (INIS)

    In this work some new, preliminary formulae for slow neutron scattering cross section calculation by heavy and light water molecules have been done. The idea was to find, from the sum which exists in well known Nelkin model, other cross sections in a more simple analytical form, so that next approximations may be possible. In order to sum a series it was starting from Euler-Mclaurin formula. Some new summation formulae have been derived there, and defined in two theorems. Extensive calculations, especially during the evaluation of residues, have been made at the CDC 3600 computer. validation of derived formulae was done by comparison with the BNL-325 results. Good agreement is shown. (author)

  12. Slow photon delay and the neutrino velocity

    CERN Document Server

    Gonzalez-Martin, Gustavo R

    2011-01-01

    Starting from the coordinate system used by Einstein to find the bending of light rays by gravitational fields we calculate the effect of the Earth gravitational energy along a hypothetical photon null path on the geoid non inertial system. There is an energy term, relative to an inertial system, which may be interpreted as a small time-relative "dressed" physical rest mass correction to the photon null mass. This relative gravitational potential energy determines a proper time delay proportional to the laboratory non inertial flying time interval along the trajectory with a small factor 5.276x10-5. Applying this delay to a hypothetical photon trajectory from the CERN SPS/CNGS target to the LNGS OPERA detector we may interpret the reported neutrino time anomaly, which is of the same order of magnitude, by saying that the OPERA neutrino is faster than our slow photon but its speed is smaller than the fundamental constant c.

  13. Slow-light-based optical frequency shifter

    Science.gov (United States)

    Li, Qian; Bao, Yupan; Thuresson, Axel; Nilsson, Adam N.; Rippe, Lars; Kröll, Stefan

    2016-04-01

    We demonstrate experimentally and theoretically a controllable way of shifting the frequency of an optical pulse by using a combination of spectral hole burning, slow light effect, and linear Stark effect in a rare-earth-ion-doped crystal. We claim that the solid angle of acceptance of a frequency shift structure can be close to 2 π , which means that the frequency shifter could work not only for optical pulses propagating in a specific spatial mode but also for randomly scattered light. As the frequency shift is controlled solely by an external electric field, it works also for weak coherent light fields and can be used, for example, as a frequency shifter for quantum memory devices in quantum communication.

  14. Slow light based optical frequency shifter

    CERN Document Server

    Li, Qian; Thuresson, Axel; Nilsson, Adam N; Rippe, Lars; Kröll, Stefan

    2016-01-01

    We demonstrate experimentally and theoretically a controllable way of shifting the frequency of an optical pulse by using a combination of spectral hole burning, slow light effect, and linear Stark effect in a rare-earth-ion doped crystal. We claim that the solid angle of acceptance of a frequency shift structure can be close to $2\\pi$, which means that the frequency shifter could work not only for optical pulses propagating in a specific spatial mode but also for randomly scattered light. As the frequency shift is controlled solely by an external electric field, it works also for weak coherent light fields, and can e.g. be used as a frequency shifter for quantum memory devices in quantum communication.

  15. Hot big bang or slow freeze?

    International Nuclear Information System (INIS)

    We confront the big bang for the beginning of the universe with an equivalent picture of a slow freeze — a very cold and slowly evolving universe. In the freeze picture the masses of elementary particles increase and the gravitational constant decreases with cosmic time, while the Newtonian attraction remains unchanged. The freeze and big bang pictures both describe the same observations or physical reality. We present a simple “crossover model” without a big bang singularity. In the infinite past space–time is flat. Our model is compatible with present observations, describing the generation of primordial density fluctuations during inflation as well as the present transition to a dark energy-dominated universe

  16. Inelastic slow neutron scattering by strontium chloride

    International Nuclear Information System (INIS)

    The ability of certain compounds to conduct electricity through a mechanism involving the mobility of ions rather than electrons has attracted a great deal of experimental and theoretical attention. Some materials with fluoride structure show a pronounced specific heat anomaly well below their melting temperature. This anomaly is a consequence of lattice disorder and is associated with the fast-ion conduction. The purpose of this paper is to present the results of the experiments in which the inelastic slow neutrons scattering (E0 = 5.2 m eV) from polycrystalline Sr Cl2 was investigated. The measurements have been taken on a time-of-flight spectrometer at WWR-S Reactor in Bucharest. Information concerning the lattice dynamics are obtained from the phonon state density G(ω). The inelastic neutron scattering spectrum shows a good separation of the frequencies of the atomic vibrations. (author)

  17. New AGS slow external beam switchyard

    International Nuclear Information System (INIS)

    The original switchyard for the Slow External Proton Beam at the AGS of Brookhaven National Laboratory incorporated two current carrying, copper septa to split the beam into three parts. These septa were each .05 mm thick and intercepted a substantial amount of beam when, as often occurs, it was necessary to split the beam across its densest region. To adjust splitting ratios and optimize losses, a complex time consuming pattern of steering adjustments using various magnets was necessary. When the question of providing a fourth beam to a new target station arose, it was clear that adding a third copper septum in the very constrained space available would lead to unacceptable increases in the radiation and control problems. In order to circumvent these difficulties, it was decided to rebuild the switchyard using much thinner electrostatic septa as splitters and to provide a greater degree of independence of the various beam segments

  18. Environmentally friendly slow-release nitrogen fertilizer.

    Science.gov (United States)

    Ni, Boli; Liu, Mingzhu; Lü, Shaoyu; Xie, Lihua; Wang, Yanfang

    2011-09-28

    To sustain the further world population, more fertilizers are required, which may become an environmental hazard, unless adequate technical and socioeconomic impacts are addressed. In the current study, slow-release formulations of nitrogen fertilizer were developed on the basis of natural attapulgite (APT) clay, ethylcellulose (EC) film, and sodium carboxymethylcellulose/hydroxyethylcellulose (CMC/HEC) hydrogel. The structural and chemical characteristics of the product were examined. The release profiles of urea, ammonium sulfate, and ammonium chloride as nitrogen fertilizer substrates were determined in soil. To further compare the release profiles of nitrogen from different fertilizer substrates, a mathematical model for nutrient release from the coated fertilizer was applied to calculate the diffusion coefficient D. The influence of the product on water-holding and water-retention capacities of soil was determined. The experimental data indicated that the product can effectively reduce nutrient loss, improve use efficiency of water, and prolong irrigation cycles in drought-prone environments. PMID:21848295

  19. Thermal slow evolution of compact objects

    CERN Document Server

    Becerra, L; Nunez, L A

    2013-01-01

    We present a comparative study on the gravitational dissipative collapse for local and nonlocal anisotropic spherical matter configurations in the slow contraction approximation. The matter contents are radiant, anisotropic (unequal stresses) spherical local and nonlocal fluids, where the heat flux is described by causal thermodynamics, leading to a consistent determination of the temperature. It is found that both, local and nonlocal, matter configurations exhibit thermal peeling when most of the radiated energy comes from the outer layers of the distribution. This peeling occurs when different signs in the velocity of fluid elements appears, giving rise to the splitting of the matter configuration. This effect emerges as a combination of convection mass transfer and radiation flux, but is the intense radiation field at the outer layers of the object that causes of the peeling. This effect seems to be more violent for nonlocal configurations and it is very sensible to the initial mass of the energy flux prof...

  20. Mechanisms for slow strengthening in granular materials

    Science.gov (United States)

    Losert; Geminard; Nasuno; Gollub

    2000-04-01

    Several mechanisms cause a granular material to strengthen over time at low applied stress. The strength is determined from the maximum frictional force F(max) experienced by a shearing plate in contact with wet or dry granular material after the layer has been at rest for a waiting time tau. The layer strength increases roughly logarithmically with tau only if a shear stress is applied during the waiting time. The mechanisms of strengthening are investigated by sensitive displacement measurements, and by imaging of particle motion in the shear zone. Granular matter can strengthen due to a slow shift in the particle arrangement under shear stress. Humidity also leads to strengthening, but is found not to be its sole cause. In addition to these time dependent effects, the static friction coefficient can also be increased by compaction of the granular material under some circumstances, and by a cycling of the applied shear stress. PMID:11088198

  1. Lead Slowing Down Spectrometer Research Plans

    Energy Technology Data Exchange (ETDEWEB)

    Warren, Glen A.; Kulisek, Jonathan A.; Gavron, Victor; Danon, Yaron; Weltz, Adam; Harris, Jason; Stewart, T.

    2013-03-22

    The MPACT-funded Lead Slowing Down Spectrometry (LSDS) project has been evaluating the feasibility of using LSDS techniques to assay fissile isotopes in used nuclear fuel assemblies. The approach has the potential to provide considerable improvement in the assay of fissile isotopic masses in fuel assemblies compared to other non-destructive techniques in a direct and independent manner. The LSDS collaborations suggests that the next step to in empirically testing the feasibility is to conduct measurements on fresh fuel assemblies to understand investigate self-attenuation and fresh mixed-oxide (MOX) fuel rodlets so we may betterto understand extraction of masses for 235U and 239Pu. While progressing toward these goals, the collaboration also strongly suggests the continued development of enabling technology such as detector development and algorithm development, thatwhich could provide significant performance benefits.

  2. Remarks on Rapid vs. Slow Star Formation

    CERN Document Server

    Ballesteros-Paredes, J; Ballesteros-Paredes, Javier; Hartmann, Lee

    2006-01-01

    Observational results and theoretical developments over the last few years have suggested that molecular cloud and star formation is relatively rapid and not strongly slowed by magnetic forces. It has recently been suggested that arguments for rapid star formation are flawed because they consider only the ages of pre-main sequence stars, and thus ignore the evolutionary lifetimes of starless cores. However, the rarity of molecular clouds without young stars in the solar neighborhood indicates that the time lag between cloud and star formation must be short, inconsistent with the above claim. We discuss problems with some observational estimates indicating long protostellar core lifetimes and large stellar age spreads in molecular clouds. We also point out some additional observational constraints which suggest that protostellar cores do not have long lifetimes before collapsing. It has also been suggested that the widths of spiral arms in external galaxies indicates the lifetime of molecular clouds, due to th...

  3. Coenzyme A Binding to the Aminoglycoside Acetyltransferase (3)-IIIb Increases Conformational Sampling of Antibiotic Binding Site

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Xiaohu [ORNL; Norris, Adrianne [University of Tennessee, Knoxville (UTK); Baudry, Jerome Y [ORNL; Serpersu, Engin H [University of Tennessee, Knoxville (UTK)

    2011-01-01

    NMR spectroscopy experiments and molecular dynamics simulations were performed to describe the dynamic properties of the aminoglycoside acetyltransferase (3)-IIIb (AAC) in its apo and coenzyme A (CoASH) bound forms. The {sup 15}N-{sup 1}H HSQC spectra indicate a partial structural change and coupling of the CoASH binding site with another region in the protein upon the CoASH titration into the apo enzyme. Molecular dynamics simulations indicate a significant structural and dynamic variation of the long loop in the antibiotic binding domain in the form of a relatively slow (250 ns), concerted opening motion in the CoASH enzyme complex and that binding of the CoASH increases the structural flexibility of the loop, leading to an interchange between several similar equally populated conformations.

  4. Age-related regulation of genes: slow homeostatic changes and age-dimension technology

    Science.gov (United States)

    Kurachi, Kotoku; Zhang, Kezhong; Huo, Jeffrey; Ameri, Afshin; Kuwahara, Mitsuhiro; Fontaine, Jean-Marc; Yamamoto, Kei; Kurachi, Sumiko

    2002-11-01

    Through systematic studies of pro- and anti-blood coagulation factors, we have determined molecular mechanisms involving two genetic elements, age-related stability element (ASE), GAGGAAG and age-related increase element (AIE), a unique stretch of dinucleotide repeats (AIE). ASE and AIE are essential for age-related patterns of stable and increased gene expression patterns, respectively. Such age-related gene regulatory mechanisms are also critical for explaining homeostasis in various physiological reactions as well as slow homeostatic changes in them. The age-related increase expression of the human factor IX (hFIX) gene requires the presence of both ASE and AIE, which apparently function additively. The anti-coagulant factor protein C (hPC) gene uses an ASE (CAGGAG) to produce age-related stable expression. Both ASE sequences (G/CAGAAG) share consensus sequence of the transcriptional factor PEA-3 element. No other similar sequences, including another PEA-3 consensus sequence, GAGGATG, function in conferring age-related gene regulation. The age-regulatory mechanisms involving ASE and AIE apparently function universally with different genes and across different animal species. These findings have led us to develop a new field of research and applications, which we named “age-dimension technology (ADT)”. ADT has exciting potential for modifying age-related expression of genes as well as associated physiological processes, and developing novel, more effective prophylaxis or treatments for age-related diseases.

  5. Proceedings of the PF slow-positron source workshop

    International Nuclear Information System (INIS)

    The workshop was held on December 21 and 22, 1993, at the National Laboratory for High Energy Physics (KEK). In the PF of KEK, the construction of the slow positron source by utilizing the 2.5 GeV electron linear accelerator has been advance, and recently, slow positrons have become to be leadable to the laboratory, though at low intensity. At the workshop, lectures were given on synchrotron radiation injector, present state of the PF slow positron source, present state of the slow positron source in ETL, conveyance of slow positron beam, accumulation of positrons, experiment of slow positron utilization, surface electron spectroscopy by slow positrons, surface study using slow positrons, positronium emission from nonmetallic surfaces, formation of positronium beam, expectation to irradiation defect research using slow positrons, application of slow positron beam to SiO2/Si system, application to electron structure research, chemical utilization of positron beam, possibility of X-ray microscope in various energy regions, and application of positron beam to thin films and artificial lattice. (K.I.)

  6. Construction report of the PF slow-positron source. 1

    International Nuclear Information System (INIS)

    The slow positron source utilizing the electron beam of the 2.5 GeV electron beam accelerator which is the synchrotron radiation injector is being constructed. The outline of the project and the present state of construction are reported. As of November, 1993, by injecting the electron beam of about 10 W to the targets for producing positrons, the slow positrons of 4 x 104 e+/s has been obtained in the laboratory. Finally, with the electron beam of 30 kW, it is aimed at to obtain the slow positron beam of 2 x 109 e+/s. In the slow positron source, the electron beam from the 2.5 GeV linear accelerator is used as the primary beam. This beam is led to the target with electromagnets. Radiation shields were strengthened, and the electrostatic lens system was attached to efficiently extract and send out slow positrons. The conveying system for slow positrons is explained. Primary electron beam, target and moderator for producing slow positrons, the change to continuous current of pulsed slow positron beam and the heightening of luminance of slow positron beam, and the experiment on the utilization of slow positron beam, and the control system for positron conveyance path are reported. (K.I.)

  7. Theory on thermodynamic coupling of site-specific DNA–protein interactions with fluctuations in DNA-binding domains

    International Nuclear Information System (INIS)

    DNA-binding proteins recognize their cognate sites on the template DNA more efficiently when the thermally driven flipping of their DNA-binding domains between the fast- and slow-moving conformations is coupled to the search dynamics. We show that there exists an optimum barrier height (∼kBT ln2) that separates these fast- and slow-moving states of DNA-binding domains, at which the efficiency associated with the thermodynamic coupling of thermally driven flipping and the overall search dynamics is the maximum. Furthermore, the dynamics of DNA-binding domains resembles that of typical downhill folding proteins at their midpoint denaturation temperatures. We further show that the average one-dimensional scanning lengths of slow- and fast-moving states of DNA-binding domains of LacI repressor protein are tuned to minimize the overall search time that is required to locate its cognate sites on DNA. (paper)

  8. Theory on thermodynamic coupling of site-specific DNA-protein interactions with fluctuations in DNA-binding domains

    Energy Technology Data Exchange (ETDEWEB)

    Murugan, R, E-mail: rmurugan@gmail.com [Department of Biotechnology, Indian Institute of Technology Madras, Chennai (India)

    2011-12-16

    DNA-binding proteins recognize their cognate sites on the template DNA more efficiently when the thermally driven flipping of their DNA-binding domains between the fast- and slow-moving conformations is coupled to the search dynamics. We show that there exists an optimum barrier height ({approx}k{sub B}T ln2) that separates these fast- and slow-moving states of DNA-binding domains, at which the efficiency associated with the thermodynamic coupling of thermally driven flipping and the overall search dynamics is the maximum. Furthermore, the dynamics of DNA-binding domains resembles that of typical downhill folding proteins at their midpoint denaturation temperatures. We further show that the average one-dimensional scanning lengths of slow- and fast-moving states of DNA-binding domains of LacI repressor protein are tuned to minimize the overall search time that is required to locate its cognate sites on DNA. (paper)

  9. Intracellular calcium movements during excitation–contraction coupling in mammalian slow-twitch and fast-twitch muscle fibers

    OpenAIRE

    Baylor, Stephen M.; Hollingworth, Stephen

    2012-01-01

    In skeletal muscle fibers, action potentials elicit contractions by releasing calcium ions (Ca2+) from the sarcoplasmic reticulum. Experiments on individual mouse muscle fibers micro-injected with a rapidly responding fluorescent Ca2+ indicator dye reveal that the amount of Ca2+ released is three- to fourfold larger in fast-twitch fibers than in slow-twitch fibers, and the proportion of the released Ca2+ that binds to troponin to activate contraction is substantially smaller.

  10. Universal design of BESIII slow control and selection of software

    International Nuclear Information System (INIS)

    This article expatiates the importance of Slow Control System in BESIII during the project BEPCII. And introduces the design of universal blue print of Slow Control, construction of computer system and principle of software selection in Slow Control System. As prefabrication of BESIII, we have finished the multi-embranchment environment monitoring system in BESII. In the system, so far the configuration software Controx2000 runs well. (authors)

  11. Slow mode shocks propagating in open and closed magnetic fields

    Institute of Scientific and Technical Information of China (English)

    吕建永; 魏奉思

    1999-01-01

    A 2-D MHD model is used to investigate the propagation of slow mode shocks in the open and closed magnetic fields of the meridional plane near the sun. The solutions demonstrate that a forward slow shock could retain its slow shock characteristics into interplanetary space in the magnetically open region; however, it can evolve into an intermediate shock through the helmet-type current sheet to the open magnetic field.

  12. Higher order slow-roll predictions for inflation

    International Nuclear Information System (INIS)

    We study the WKB approximation beyond leading order for cosmological perturbations during inflation. To first order in the slow-roll parameters, we show that an improved WKB approximation leads to analytical results agreeing to within 0.1% with the standard slow-roll results. Moreover, the leading WKB approximation to second order in the slow-roll parameters leads to analytical predictions in qualitative agreement with those obtained by the Green's function method

  13. "Slow" myosins in vertebrate skeletal muscle. An immunofluorescence study

    OpenAIRE

    1980-01-01

    Specific antisera were raised in rabbits against column-purified myosins from a slow avian muscle, the chicken anterior latissimus dorsi (ALD), and a slow-twitch mammalian muscle, the guinea pig soleus (SOL). The antisera were labeled with fluorescein and applied to sections of muscles from various vertebrae species. Two distinct categories of the slow fibers were identified on the basis of their differential reactivity with the two antisera. Fibers stained by anti-ALD appear to correspond in...

  14. Slow-light enhanced gain in active photonic crystal waveguides

    OpenAIRE

    Ek, Sara; Lunnemann, Per; Chen, Yaohui; Semenova, Elizaveta; Yvind, Kresten; Mørk, Jesper

    2014-01-01

    Slow light is a fascinating physical effect, raising fundamental questions related to our understanding of light-matter interactions as well as offering new possibilities for photonic devices. From the first demonstrations of slow light propagation in ultra-cold atomic gasses, solid-state Ruby and photonic crystal structures, focus has shifted to applications, with slow light offering the ability to enhance and control light-matter interactions. The demonstration of tuneable delay lines, enha...

  15. Comments on 'Balance and the slow quasimanifold: some explicit results'

    OpenAIRE

    Saujani, Simal; Shepherd, Theodore G.

    2002-01-01

    The concept of slow vortical dynamics and its role in theoretical understanding is central to geophysical fluid dynamics. It leads, for example, to “potential vorticity thinking” (Hoskins et al. 1985). Mathematically, one imagines an invariant manifold within the phase space of solutions, called the slow manifold (Leith 1980; Lorenz 1980), to which the dynamics are constrained. Whether this slow manifold truly exists has been a major subject of inquiry over the past 20 years. It has become cl...

  16. Dopa Responsive Slow Orthostatic Tremor in Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Suk Yoon Lee

    2011-10-01

    Full Text Available Slow orthostatic tremor (OT occurred to longer and lower frequency regular rhythmic bursts in leg muscle upon standing. The slow OT was often able to clinically confused with orthostatic myoclonus. We described a Parkinson’s disease patient with levodopa responsive slow OT. She showed abnormal movements of more regular rhythms and stable frequency on both legs on standing. These symptoms were aggravated at off state and improved by increasing levodopa.

  17. Enhancement of sleep slow waves: underlying mechanisms and practical consequences.

    OpenAIRE

    Michele Bellesi; Garcia-Molina, Gary N.

    2014-01-01

    Even modest sleep restriction, especially the loss of sleep slow wave activity, is invariably associated with slower EEG activity during wake, the occurrence of local sleep in an otherwise awake brain, and impaired performance due to cognitive and memory deficits. Recent studies not only confirm the beneficial role of sleep in memory consolidation, but also point to a specific role for sleep slow waves. Thus, the implementation of methods to enhance sleep slow waves without unwanted arousals ...

  18. Fast and slow metabolizers of Hoasca.

    Science.gov (United States)

    Callaway, J C

    2005-06-01

    Harmine, a major alkaloid in ayahuasca (hoasca), is a selective and reversible inhibitor of the enzyme monoamine oxidase-A (MAO-A). It is also a selective inhibitor of the human cytochrome P450 isozyme 2D6 (CYP 2D6), which metabolizes harmine to a more hydrophilic derivative for eventual excretion. CYP 2D6 exhibits a wide range of polymorphisms in human populations, and variations in this enzymatic activity could account for differences in effects between individuals who use hoasca. This report broadly describes two subgroups of CYP 2D6 phenotypes--i.e., fast and slow metabolizers of harmine-in 14 experienced male members of the União do Vegetal (UDV) who received a standardized dosage of hoasca. To compensate for metabolic variations in their normal religious practice, the administered dose of hoasca is always determined by the presiding mestre, who is responsible for deciding the actual amount for each individual. This age-old method compensates for metabolic variations between individuals and variations in both the alkaloid profile and strength of the hoasca. PMID:16149329

  19. Slow Diffusive Gravitational Instability Before Decoupling

    CERN Document Server

    Thompson, Todd A

    2009-01-01

    Radiative diffusion damps acoustic modes at large comoving wavenumber (k) before decoupling (``Silk damping''). In a simple WKB analysis, neglecting moments of the temperature distribution beyond the quadrupole, damping appears in the acoustic mode as a term of order ik^2/(taudot) where taudot is the scattering rate per unit conformal time. Although the Jeans instability is stabilized on scales smaller than the adiabatic Jeans length, I show that the medium is linearly unstable to first order in (1/taudot) to a slow diffusive mode. At large comoving wavenumber, the characteristic growth rate becomes independent of spatial scale and constant: (t_{KH}a)^-1 ~ (128 pi G/9 kappa_T c)(rho_m/rho_b), where "a" is the scale factor, rho_m and rho_b are the matter and baryon energy density, respectively, and kappa_T is the Thomson opacity. This is the characteristic timescale for a fluid parcel to radiate away its thermal energy content at the Eddington limit, analogous to the Kelvin-Helmholz (KH) time for a massive sta...

  20. Commodity chemical growth to slow in 1993

    International Nuclear Information System (INIS)

    In their latest chemical outlook, DRI/McGraw-Hill economists characterize 1992 as a peak year for U.S. commodity chemical demand growth, at 4.2%, tapering off to a compound 2.2% between 1993 and 1995. Just as operating rates begin to reach higher levels in 1995, however, DRI forecasts slowing GNP growth. DRI's Ramunas J. Svarcas expects a decline in exports. Those plastics promising the rosiest consumption outlook include melamine-formaldehyde resin, up 9.9% in 1992, from 155 million lbs in 1991, and projected to grow 8.6%/year through 1995; styrene acrylonitrile resin, up 23% this year, from 58 million lbs last year, and growing 8.2%/year through 1995; and unsaturated polyester, up 11.7% this year, from 1.07 billion lbs in 1991, and increasing at 6.5%/year. Methanol is a bright spot, with consumption growing 4.7%, from 11.2 billion lbs in 1991 and 12%/year thereafter. Ortho-xylene managed an impressive 21% rebound from a depressed 1991 level of 783 million lbs, and is expected to continue its recovery at 7.7%/year

  1. Development of slow, polarized positron beam

    International Nuclear Information System (INIS)

    In Tokyo Metropolitan University, the precision verification of quantum electrodynamics has been carried out, paying attention to the experimental result of Michigan University. Based on the experience of a series of these positron experiments, the development of slow, polarized positron beam was begun in fiscal year 1994. It was found that the experiment on the formation of polarized positrons has been rarely performed, therefore, it was considered to advance the basic examination on the polarization of positrons and to construct the equipment that can measure accurately the degree of polarization. The polarized positron formation system which is being constructed at present is explained. The multiple scattering when positrons pass through an Al target and the change of spin direction by it were calculated, assuming no decrease of polarization in Al. The general simulation program POEM was made for treating spin motion. Zeeman effect and the instrument for measuring the degree of polarization 'POPAI' are described. The verification of the conservation law in lepton sector, the verification of biomolecule chirality and the elucidation of spin state at artificial multi-layer film interface are planned to be studied. (K.I.)

  2. Review of slow-wave structures

    Science.gov (United States)

    Wallett, Thomas M.; Qureshi, A. Haq

    1994-06-01

    The majority of recent theoretical and experimental reports published in the literature dealing with helical slow-wave structures focus on the dispersion characteristics and their effects due to the finite helix wire thickness and attenuation, dielectric loading, metal loading, and the introduction of plasma. In many papers, an effective dielectric constant is used to take into account helix wire dimensions and conductivity losses, while the propagation constant of the signal and the interaction impedance of the structure are found to depend on the surface resistivity of the helix. Also, various dielectric supporting rods are simulated by one or several uniform cylinders having an effective dielectric constant, while metal vane loading and plasma effects are incorporated in the effective dielectric constant. The papers dealing with coupled cavities and folded or loaded wave guides describe equivalent circuit models, efficiency enhancement, and the prediction of instabilities for these structures. Equivalent circuit models of various structures are found using computer software programs SUPERFISH and TOUCHSTONE. Efficiency enhancement in tubes is achieved through dynamic velocity and phase adjusted tapers using computer techniques. The stability threshold of unwanted antisymmetric and higher order modes is predicted using SOS and MAGIC codes and the dependence of higher order modes on beam conductance, section length, and effective Q of a cavity is shown.

  3. Review of Slow-Wave Structures

    Science.gov (United States)

    Wallett, Thomas M.; Qureshi, A. Haq

    1994-01-01

    The majority of recent theoretical and experimental reports published in the literature dealing with helical slow-wave structures focus on the dispersion characteristics and their effects due to the finite helix wire thickness and attenuation, dielectric loading, metal loading, and the introduction of plasma. In many papers, an effective dielectric constant is used to take into account helix wire dimensions and conductivity losses, while the propagation constant of the signal and the interaction impedance of the structure are found to depend on the surface resistivity of the helix. Also, various dielectric supporting rods are simulated by one or several uniform cylinders having an effective dielectric constant, while metal vane loading and plasma effects are incorporated in the effective dielectric constant. The papers dealing with coupled cavities and folded or loaded wave guides describe equivalent circuit models, efficiency enhancement, and the prediction of instabilities for these structures. Equivalent circuit models of various structures are found using computer software programs SUPERFISH and TOUCHSTONE. Efficiency enhancement in tubes is achieved through dynamic velocity and phase adjusted tapers using computer techniques. The stability threshold of unwanted antisymmetric and higher order modes is predicted using SOS and MAGIC codes and the dependence of higher order modes on beam conductance, section length, and effective Q of a cavity is shown.

  4. Sharp Slow Waves in the EEG.

    Science.gov (United States)

    Janati, A Bruce; AlGhasab, Naif Saad; Alshammari, Raed Ayed; saad AlGhassab, Abdulmohsen; Al-Aslami Yossef Fahad

    2016-06-01

    There exists a paucity of data in the EEG literature on characteristics of "atypical" interictal epileptiform discharges (IEDs), including sharp slow waves (SSWs). This article aims to address the clinical, neurophysiological, and neuropathological significance of SSW The EEGs of 920 patients at a tertiary-care facility were prospectively reviewed over a period of one year. Thirty-six patients had SSWs in their EEG. Of these, 6 patients were excluded because of inadequate clinical data. The clinical and neuroimaging data of the remaining 30 patients were then retrospectively collected and reviewed, and the findings were correlated. The data revealed that SSWs were rare and age-related EEG events occurring primarily in the first two decades of life. All patients with SSWs had documented epilepsy, presenting clinically with partial or generalized epilepsy. It is notable that one-third of the patients with SSWs had chronic or static central nervous system (CNS) pathology, particularly congenital CNS anomalies. Though more than one mechanism may be involved in the pathogenesis of SSWs, this research indicates that the most compelling theory is a deeply seated cortical generator giving rise to this EEG pattern. The presence of SSWs should alert clinicians to the presence of partial or generalized epilepsy or an underlying chronic or static CNS pathology, in particular congenital CNS anomalies, underscoring the significance of brain magnetic resonance imaging in the work-up of this population. PMID:27373055

  5. Slow positron beam at the JINR, Dubna

    Directory of Open Access Journals (Sweden)

    Horodek Paweł

    2015-12-01

    Full Text Available The Low Energy Positron Toroidal Accumulator (LEPTA at the Joint Institute for Nuclear Research (JINR proposed for generation of positronium in flight has been adopted for positron annihilation spectroscopy (PAS. The positron injector generates continuous slow positron beam with positron energy range between 50 eV and 35 keV. The radioactive 22Na isotope is used. In distinction to popular tungsten foil, here the solid neon is used as moderator. It allows to obtain the beam intensity of about 105 e+/s width energy spectrum characterized by full width at half maximum (FWHM of 3.4 eV and a tail to lower energies of about 30 eV. The paper covers the characteristic of variable energy positron beam at the LEPTA facility: parameters, the rule of moderation, scheme of injector, and transportation of positrons into the sample chamber. Recent status of the project and its development in the field of PAS is discussed. As an example, the measurement of the positron diffusion length in pure iron is demonstrated.

  6. Void formation and roughening in slow fracture.

    Science.gov (United States)

    Afek, Itai; Bouchbinder, Eran; Katzav, Eytan; Mathiesen, Joachim; Procaccia, Itamar

    2005-06-01

    Slow crack propagation in ductile, and in certain brittle materials, appears to take place via the nucleation of voids ahead of the crack tip due to plastic yields, followed by the coalescence of these voids. Postmortem analysis of the resulting fracture surfaces of ductile and brittle materials on the microm-mm and the nm scales, respectively, reveals self-affine cracks with anomalous scaling exponent zeta approximately = 0.8 in 3 dimensions and zeta approximately = 0.65 in 2 dimensions. In this paper we present an analytic theory based on the method of iterated conformal maps aimed at modelling the void formation and the fracture growth, culminating in estimates of the roughening exponents in 2 dimensions. In the simplest realization of the model we allow one void ahead of the crack, and address the robustness of the roughening exponent. Next we develop the theory further, to include two voids ahead of the crack. This development necessitates generalizing the method of iterated conformal maps to include doubly connected regions (maps from the annulus rather than the unit circle). While mathematically and numerically feasible, we find that the employment of the stress field as computed from elasticity theory becomes questionable when more than one void is explicitly inserted into the material. Thus further progress in this line of research calls for improved treatment of the plastic dynamics. PMID:16089840

  7. Nanodots formation with slow highly charged ions

    Energy Technology Data Exchange (ETDEWEB)

    Yamazaki, Yasunori [Graduate School of Arts and Sciences, University of Tokyo and RIKEN (Japan)

    2007-06-15

    We have been developing a compact electron beam ion source with a high-T{sub c}superconductor as a solenoid magnet, which can be operated at liquid nitrogen temperature, and can deliver slow highly-charged ions as high as q 42. With this ion source together with other ion sources, nanodot formation processes were studied for a highly oriented pyrolytic graphite (HOPG) plate as a target. The impact site was observed with both the scanning tunnelling microscope (STM) mode and non-contact atomic force microscope (NCAFM) mode. It was found that protrusion-like dots were observed for both modes at the same position, and one HCI induced one dot. The dot size (diameter) and height were observed to be more or less the same for both modes, i.e, an HCI impact induces topographic modification on the HOPG surface. The dot size and height were measured as functions of the charge state (q = 8-46) and the kinetic energy (E = 1-300 keV) of highly-charged ions. It was found that the dot size increased linearly with the charge state, although the dependence on the kinetic energy was very weak if any.

  8. Formation of 11-trans slow reacting substances.

    Science.gov (United States)

    Atrache, V; Sok, D E; Pai, J K; Sih, C J

    1981-01-01

    Under strongly basic conditions [excess LiOH, dimethoxyethane/water (4:1, vol/vol)], purified slow reacting substances (SRSs) SRS-GSH and SRS-Cys were not isomerized to their corresponding 11-trans isomers. However, addition of thiols such as glutathione (GSH) or L-cysteine to this basic medium produced various amounts of 11-trans-SRS, depending on the thiol concentration. This chemical isomerization was inhibited by the radical scavenger 4-hydroxy-2,2,6,6-tetramethylpiperidinooxy free radical (HTMP); the inhibition suggests that the thiyl radical (RS) is added reversibly to the triene system at C-12, resulting in the overall cis leads to trans isomerization of the 11,12 double bond. Because the amount of 11-trans-SRS-Cys produced by intact rat basophilic leukemia (RBL-1) cells was consistently higher than the amount produced in boiled cells, we believe that intact RBL-1 cells contain enzyme systems that form peroxides, which are known to enhance the formation of thiyl radicals, required for cis leads to trans isomerization. Likewise, HTMP inhibited the formation of 11-trans-SRS-Cys in this cell system. PMID:6112746

  9. On Promoting the Slow Learners' Learning in English Class

    Institute of Scientific and Technical Information of China (English)

    庞雅

    2011-01-01

    Nowadays,the actualities of slow learners in English class are not satisfying in China.Confronted with such kind of situation,as language teachers,how to promote the slow students' learning,is one of the biggest problems in our teaching.The paper focuses on the features of slow learners,e.g.,lit'de or improper motivation,debilitative anxiety,introversion,inhibition,etc.and the roles the slow learners play in English class,and some of the writer's personal suggestions for promoting their learning in English class as well.

  10. Application of Planar Broadband Slow-Wave Systems

    Directory of Open Access Journals (Sweden)

    Edvardas Metlevskis

    2012-04-01

    Full Text Available Different types of planar broadband slow-wave systems are used for designing microwave devices. The papers published by Lithuanian scientists analyze and investigate the models of helical and meander slow-wave systems. The article carefully examines the applications of meander slow-wave systems and presents the areas where similar systems, e.g. mobile devices, RFID, wireless technologies are used and reviewed nowadays. The paper also focuses on the examples of the papers discussing antennas, filters and couplers that contain designed and fabricated meander slow-wave systems.Article in Lithuanian

  11. Production of slow positrons using an electron linac

    International Nuclear Information System (INIS)

    Intense pulsed slow-positron beams have been produced using electron linac beams of energy 25 MeV. Slow positorons were counted by complete separation from strong flashed signals produced directly by the primary electron pulsed beam. The yield of low-energy positrons was estimated as 2x106 slow positrons per second. The conversion efficiency of slow-positron production for 25 MeV electrons, epsilon, was 2.4x10-8, much lower than the value obtained by Howell et al. Several methods of overcoming the difficulties of practical application were attempted, and are discussed in the paper. (author)

  12. Threshold Characteristics of Slow-Light Photonic Crystal Lasers

    DEFF Research Database (Denmark)

    Xue, Weiqi; Yu, Yi; Ottaviano, Luisa;

    2016-01-01

    The threshold properties of photonic crystal quantum dot lasers operating in the slow-light regime are investigated experimentally and theoretically. Measurements show that, in contrast to conventional lasers, the threshold gain attains a minimum value for a specific cavity length. The experimental...... results are explained by an analytical theory for the laser threshold that takes into account the effects of slow light and random disorder due to unavoidable fabrication imperfections. Longer lasers are found to operate deeper into the slow-light region, leading to a trade-off between slow-light induced...

  13. Python bindings for libcloudph++

    OpenAIRE

    Jarecka, Dorota; Arabas, Sylwester; Del Vento, Davide

    2015-01-01

    This technical note introduces the Python bindings for libcloudph++. The libcloudph++ is a C++ library of algorithms for representing atmospheric cloud microphysics in numerical models. The bindings expose the complete functionality of the library to the Python users. The bindings are implemented using the Boost.Python C++ library and use NumPy arrays. This note includes listings with Python scripts exemplifying the use of selected library components. An example solution for using the Python ...

  14. Inhibitory effects of three diketopiperazines from marine-derived bacteria on endothelial protein C receptor shedding in human endothelial cells and mice.

    Science.gov (United States)

    Lee, Wonhwa; Ku, Sae-Kwang; Choi, Hyukjae; Bae, Jong-Sup

    2016-04-01

    Diketopiperazine is a natural products found from bacteria, fungi, marine sponges, gorgonian and red algae. They are cyclic dipeptides possessing relatively simple and rigid structures with chiral nature and various side chains. The compounds in this structure class have been known to possess diverse bioactivities including antibiotic activity, anti-cancer activity, neuroprotective activity, and anti-inflammatory activity. The endothelial cell protein C receptor (EPCR) plays an important role in the cytoprotective pathway and in the activation of protein C. Endothelial cell protein C receptor (EPCR) can be shed from the cell surface, which is mediated by tumor necrosis factor-α converting enzyme (TACE). However, little is known about the effects of diketopiperazine on EPCR shedding. We investigated this issue by monitoring the effects of diketopiperazine on phorbol-12-myristate 13-acetate (PMA)-, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β-induced EPCR shedding in human umbilical vein endothelial cells (HUVECs), and cecal ligation and puncture (CLP)-mediated EPCR shedding in mice and underlying mechanism. Here, three (1-3) of diketopiperazines were isolated from two strains of marine-derived bacteria and 1-3 induced potent inhibition of PMA-, TNF-α-, IL-1β (in HUVECs), and CLP-induced EPCR shedding (in mice) via inhibition of phosphorylation of mitogen-activated protein kinases (MAPKs) such as p38, janus kinase (JNK), and extracellular signal-regulated kinase (ERK) 1/2. 1-3 also inhibited the expression and activity of PMA-induced TACE in HUVECs suggesting that p38, ERK1/2, and JNK could be molecular targets of 1-3. These results demonstrate the potential of 1-3 as an anti-EPCR shedding reagent against PMA-mediated and CLP-mediated EPCR shedding. PMID:27012760

  15. Deficiency of CCAAT/Enhancer Binding Protein-Epsilon Reduces Atherosclerotic Lesions in LDLR−/− Mice

    OpenAIRE

    Okamoto, Ryoko; Gery, Sigal; Gombart, Adrian F.; Wang, Xuping; Castellani, Lawrence W.; Akagi, Tadayuki; Chen, Shuang; Arditi, Moshe; Ho, Quoc; Lusis, Aldons J.; Li, Quanlin; Koeffler, H. Phillip

    2014-01-01

    The CCAAT/enhancer binding proteins (C/EBPs) are transcription factors involved in hematopoietic cell development and induction of several inflammatory mediators. C/EBPε is expressed only in myeloid cells including monocytes/macrophages. Atherosclerosis is an inflammatory disorder of the vascular wall and circulating immune cells such as monocytes/macrophages. Mice deficient in the low density lipoprotein (LDL) receptor (Ldlr−/−) fed on a high cholesterol diet (HCD) show elevated blood choles...

  16. The CCAAT/enhancer binding protein and its role in adipocyte differentiation: evidence for direct involvement in terminal adipocyte development.

    OpenAIRE

    Samuelsson, L; Strömberg, K; Vikman, K; Bjursell, G; Enerbäck, S

    1991-01-01

    During the course of differentiation of preadipocytes into adipocytes, several differentiation-linked genes are activated synchronously with morphological changes. To follow this process we have used 3T3-F442A cells, known to undergo adipocyte conversion with high frequency. Accumulation of lipid droplets in the cytoplasm constitutes an easily visualized sign of the terminally differentiated phenotype. In this report we demonstrate that expression of the CCAAT/enhancer binding protein (C/EBP)...

  17. DNS & Bind Cookbook

    CERN Document Server

    Liu, Cricket

    2011-01-01

    The DNS & BIND Cookbook presents solutions to the many problems faced by network administrators responsible for a name server. Following O'Reilly's popular problem-and-solution cookbook format, this title is an indispensable companion to DNS & BIND, 4th Edition, the definitive guide to the critical task of name server administration. The cookbook contains dozens of code recipes showing solutions to everyday problems, ranging from simple questions, like, "How do I get BIND?" to more advanced topics like providing name service for IPv6 addresses. It's full of BIND configuration files that yo

  18. Python bindings for libcloudph++

    CERN Document Server

    Jarecka, Dorota; Del Vento, Davide

    2015-01-01

    This technical note introduces the Python bindings for libcloudph++. The libcloudph++ is a C++ library of algorithms for representing atmospheric cloud microphysics in numerical models. The bindings expose the complete functionality of the library to the Python users. The bindings are implemented using the Boost.Python C++ library and use NumPy arrays. This note includes listings with Python scripts exemplifying the use of selected library components. An example solution for using the Python bindings to access libcloudph++ from Fortran is presented.

  19. A Comparative Analysis of the Mechanism of Toll-Like Receptor-Disruption by TIR-Containing Protein C from Uropathogenic Escherichia coli.

    Science.gov (United States)

    Waldhuber, Anna; Snyder, Greg A; Römmler, Franziska; Cirl, Christine; Müller, Tina; Xiao, Tsan Sam; Svanborg, Catharina; Miethke, Thomas

    2016-01-01

    The TIR-containing protein C (TcpC) of uropathogenic Escherichia coli strains is a powerful virulence factor by impairing the signaling cascade of Toll-like receptors (TLRs). Several other bacterial pathogens like Salmonella, Yersinia, Staphylococcus aureus but also non-pathogens express similar proteins. We discuss here the pathogenic potential of TcpC and its interaction with TLRs and TLR-adapter proteins on the molecular level and compare its activity with the activity of other bacterial TIR-containing proteins. Finally, we analyze and compare the structure of bacterial TIR-domains with the TIR-domains of TLRs and TLR-adapters. PMID:26938564

  20. A Comparative Analysis of the Mechanism of Toll-Like Receptor-Disruption by TIR-Containing Protein C from Uropathogenic Escherichia coli

    Directory of Open Access Journals (Sweden)

    Anna Waldhuber

    2016-02-01

    Full Text Available The TIR-containing protein C (TcpC of uropathogenic Escherichia coli strains is a powerful virulence factor by impairing the signaling cascade of Toll-like receptors (TLRs. Several other bacterial pathogens like Salmonella, Yersinia, Staphylococcus aureus but also non-pathogens express similar proteins. We discuss here the pathogenic potential of TcpC and its interaction with TLRs and TLR-adapter proteins on the molecular level and compare its activity with the activity of other bacterial TIR-containing proteins. Finally, we analyze and compare the structure of bacterial TIR-domains with the TIR-domains of TLRs and TLR-adapters.

  1. Structure and function of complement protein C1q and its role in the development of autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Katarzyna Smykał-Jankowiak

    2009-09-01

    Full Text Available Complement plays an important role in the immune system. Three different pathways of complement activation are known: the classical, alternative, and lectin dependent. They involve more than 30 serum peptides. C1q is the first subcomponent of the classical pathway of complement activation. It is composed of three types of chains, A, B, and C, which form a molecule containing 18 peptides. Each of the chains has a short amino-terminal region followed by a collagen-like region (playing a role in the activation of C1r2C1s2 and a carboxy-terminal head, which binds to immune complexes. Recent studies have shown a great number of ligands for C1q, including aggregated IgG, IgM, human T-cell lymphotropic virus-I (HTLV-I, gp21 peptide, human immunodeficiency virus-1 (HIV-1 gp21 peptide, β-amyloid, fragments of bacterial walls, apoptotic cells, and many others. However, the role of C1q is not only associated with complement activation. It also helps in the removal of immune complexes and necrotic cells, stimulates the production of some cytokines, and modulates the function of lymphocytes. Complete C1q deficiency is a rare genetic disorder. The C1q gene is located on the short arm of chromosome 1. So far, only a few mutations in C1q gene have been reported. The presence of these mutations is strongly associated with recurrent bacterial infections and the development of systemic lupus erythematosus (SLE. Recent clinical studies point to the significance of anti-C1q antibodies in the diagnosis and assessment of lupus nephritis activity.

  2. Mutual recombination in slow Si+ + H- collisions

    Institute of Scientific and Technical Information of China (English)

    Wang Jian-Guo; Liu Chun-Lei; Janev R. K.; Yan Jun; Shi Jian-Rong

    2006-01-01

    This paper studies the process of mutual neutralization of Si+ and H- ions in slow collisions within the multichannel Landau-Zener model. All important ionic-covalent couplings in this collision system are included in the collision dynamics. The cross sections for population of specific final states of product Si atom are calculated in the CM energy range 0.05 eV/u-5 keV/u. Both singlet and triplet states are considered. At collision energies below ~10 eV/u, the most populated singlet state is Si(3p4p, 1S0), while for energies above ~150eV/u it is the Si(3p, 4p, 1P1) state. In the case of triplet states, the mixed 3p4p(3 S1 +3P0) states are the most populated in the entire collision energy range investigated. The total cross section exhibits a broad maximum around 200-300 eV/u and for ECM ≤ 10eV/u it monotonically increases with decreasing the collision energy, reaching a value of 8 × 10-13 cm2 at ECM = 0.05 eV/u. The ion-pair formation process in Si(3p2 3PJ)+H(1s) collisions has also been considered and its cross section in the considered energy range is very small (smaller than 10-20 cm2 in the energy region below 1 keV/u).

  3. Melanin-binding radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Packer, S; Fairchild, R G; Watts, K P; Greenberg, D; Hannon, S J

    1980-01-01

    The scope of this paper is limited to an analysis of the factors that are important to the relationship of radiopharmaceuticals to melanin. While the authors do not attempt to deal with differences between melanin-binding vs. melanoma-binding, a notable variance is assumed. (PSB)

  4. Melanin-binding radiopharmaceuticals

    International Nuclear Information System (INIS)

    The scope of this paper is limited to an analysis of the factors that are important to the relationship of radiopharmaceuticals to melanin. While the authors do not attempt to deal with differences between melanin-binding vs. melanoma-binding, a notable variance is assumed

  5. DNS BIND Server Configuration

    Directory of Open Access Journals (Sweden)

    Radu MARSANU

    2011-01-01

    Full Text Available After a brief presentation of the DNS and BIND standard for Unix platforms, the paper presents an application which has a principal objective, the configuring of the DNS BIND 9 server. The general objectives of the application are presented, follow by the description of the details of designing the program.

  6. Experimental determination of the slow-neutron wavelength distribution

    DEFF Research Database (Denmark)

    Lebech, Bente; Mikke, K.; Sledziewska-Blocka, D.

    1970-01-01

    Different experiments for determining the slow-neutron wavelength distribution in the region 227-3 meV have been carried out, and the results compared. It is concluded that the slow-neutron wave-length distribution can be determined accurately by elastic scattering on a pure incoherent or a pure...

  7. Tetranectin in slow intra- and extrafusal chicken muscle fibers

    DEFF Research Database (Denmark)

    Xu, X; Gilpin, B; Iba, K;

    2001-01-01

    heavy chains (MHC) and double immunostaining techniques, we found that tetranectin was restricted to slow (type I) muscle fibers. Similarly only slow intrafusal fibers accumulated tetranectin. The pattern of immunostaining in chickens differs markedly from that seen in mouse muscles, indicating that...... tetranectin performs a role in muscle that is not associated with a hitherto recognized muscle type or function....

  8. Superconducting niobium thin film slow-wave structures

    Science.gov (United States)

    Bautista, J. J.; Petty, S. M.; Allen, L. H.; Beasley, M. R.; Hammond, R. H.

    1983-01-01

    A superconducting comb structure as a slow-wave element in a traveling-wave maser will significantly improve maser noise temperature and gain by reducing the insertion loss. The results of the insertion loss measurements of superconducting niobium slow-wave structures subjected to maser operating conditions at X-Band frequencies are presented.

  9. Problems Associated with the Monochromatisation of Slow Neutrons

    International Nuclear Information System (INIS)

    The paper sets out the result of calculations to determine the shape of the spectral line of twin-rotor, pulsing, slow-neutron monochromators, as a function of the shifts in the phases between the rotors. Consideration is also given to die possibility of using certain light elements as slow-neutron filters. (author)

  10. C-Terminal Charge-Reversal Derivatization and Parallel Use of Multiple Proteases Facilitates Identification of Protein C-Termini by C-Terminomics.

    Science.gov (United States)

    Somasundaram, Prasath; Koudelka, Tomas; Linke, Dennis; Tholey, Andreas

    2016-04-01

    The identification of protein C-termini in complex proteomes is challenging due to the poor ionization efficiency of the carboxyl group. Amidating the negatively charged C-termini with ethanolamine (EA) has been suggested to improve the detection of C-terminal peptides and allows for a directed depletion of internal peptides after proteolysis using carboxyl reactive polymers. In the present study, the derivatization with N,N-dimethylethylenediamine (DMEDA) and (4-aminobutyl)guanidine (AG) leading to a positively charged C-terminus was investigated. C-terminal charge-reversed peptides showed improved coverage of b- and y-ion series in the MS/MS spectra compared to their noncharged counterparts. DMEDA-derivatized peptides resulted in many peptides with charge states of 3+, which benefited from ETD fragmentation. This makes the charge-reversal strategy particularly useful for the analysis of protein C-termini, which may also be post-translationally modified. The labeling strategy and the indirect enrichment of C-termini worked with similar efficiency for both DMEDA and EA, and their applicability was demonstrated on an E. coli proteome. Utilizing two proteases and different MS/MS activation mechanisms allowed for the identification of >400 C-termini, encompassing both canonical and truncated C-termini. PMID:26939532

  11. Damping of Slow Magnetoacoustic Waves in an Inhomogeneous Coronal Plasma

    Indian Academy of Sciences (India)

    Nagendra Kumar; Pradeep Kumar; Shiv Singh; Anil Kumar

    2008-03-01

    We study the propagation and dissipation of slow magnetoacoustic waves in an inhomogeneous viscous coronal loop plasma permeated by uniform magnetic field. Only viscosity and thermal conductivity are taken into account as dissipative processes in the coronal loop. The damping length of slow-mode waves exhibit varying behaviour depending upon the physical parameters of the loop in an active region AR8270 observed by TRACE. The wave energy flux associated with slow magnetoacoustic waves turns out to be of the order of 106 erg cm-2 s-1 which is high enough to replace the energy lost through optically thin coronal emission and the thermal conduction belowto the transition region. It is also found that only those slow-mode waves which have periods more than 240 s provide the required heating rate to balance the energy losses in the solar corona. Our calculated wave periods for slow-mode waves nearly match with the oscillation periods of loop observed by TRACE.

  12. Performance study of the Beijing intense slow positron beam

    International Nuclear Information System (INIS)

    A slow positron beam based on the Beijing Electron-Positron Collider (BEPC) has been constructed and tested. In this paper, transmission efficiency and other performance parameters of the system are measured by a series of experiments on the pulsed slow positron beam. Results show that the transmission efficiency of the transfer system is above 98% and the size of pulsed slow positron beam's image got by the IP is less than 15 mm. At the same time, the energy spread of the pulsed slow positron beam is about 10 eV (FWHM). The pulsed beam intensity is about 106 slow positrons/s when BEPC is running under the short-pulse mode. It is also shown that the intensity would be reduced to half of initial value after storing 40 ms at 3 x 10-7 Pa vacuum level. (authors)

  13. Origin of Pseudotachylites during slow creep experiments

    Science.gov (United States)

    Peč, M.; Stünitz, H.; Heilbronner, R.; Drury, M.; De Capitani, C.

    2012-04-01

    melting temperatures. Thus, it seems that melting is a continuation of the comminution once the rock has reached small enough grain size. We therefore suggest that pseudotachylites may also form as 'mechanical melts' at slow displacement rates without the necessity of reaching high temperatures.

  14. Slow dynamics of the amphibian tympanic membrane

    Science.gov (United States)

    Bergevin, Christopher; Meenderink, Sebastiaan W. F.; van der Heijden, Marcel; Narins, Peter M.

    2015-12-01

    Several studies have demonstrated that delays associated with evoked otoacoustic emissions (OAEs) largely originate from filter delays of resonant elements in the inner ear. However, one vertebrate group is an exception: Anuran (frogs and toads) amphibian OAEs exhibit relatively long delays (several milliseconds), yet relatively broad tuning. These delays, also apparent in auditory nerve fiber (ANF) responses, have been partially attributed to the middle ear (ME), with a total forward delay of ˜0.7 ms (˜30 times longer than in gerbil). However, ME forward delays only partially account for the longer delays of OAEs and ANF responses. We used scanning laser Doppler vibrometery to map surface velocity over the tympanic membrane (TyM) of anesthetized bullfrogs (Rana catesbeiana). Our main finding is a circularly-symmetric wave on the TyM surface, starting at the outer edges of the TyM and propagating inward towards the center (the site of the ossicular attachment). This wave exists for frequencies ˜0.75-3 kHz, overlapping the range of bullfrog hearing (˜0.05-1.7 kHz). Group delays associated with this wave varied from 0.4 to 1.2 ms and correlated with with TyM diameter, which ranged from ˜6-16 mm. These delays correspond well to those from previous ME measurements. Presumably the TyM waves stem from biomechanical constraints of semi-aquatic species with a relatively large tympanum. We investigated some of these constraints by measuring the pressure ratio across the TyM (˜10-30 dB drop, delay of ˜0.35 ms), the effects of ossicular interruption, the changes due to physiological state of TyM (`dry-out'), and by calculating the middle-ear input impedance. In summary, we found a slow, inward-traveling wave on the TyM surface that accounts for a substantial fraction of the relatively long otoacoustic and neurophysiological delays previously observed in the anuran inner ear.

  15. Enhancement of sleep slow waves: underlying mechanisms and practical consequences.

    Directory of Open Access Journals (Sweden)

    Michele Bellesi

    2014-10-01

    Full Text Available Even modest sleep restriction, especially the loss of sleep slow wave activity, is invariably associated with slower EEG activity during wake, the occurrence of local sleep in an otherwise awake brain, and impaired performance due to cognitive and memory deficits. Recent studies not only confirm the beneficial role of sleep in memory consolidation, but also point to a specific role for sleep slow waves. Thus, the implementation of methods to enhance sleep slow waves without unwanted arousals or lightening of sleep could have significant practical implications. Here we first review the evidence that it is possible to enhance sleep slow waves in humans using transcranial direct-current stimulation and transcranial magnetic stimulation. Since these methods are currently impractical and their safety is questionable, especially for chronic long-term exposure, we then discuss novel data suggesting that it is possible to enhance slow waves using sensory stimuli. We consider the physiology of the K-complex, a peripheral evoked slow wave, and show that, among different sensory modalities, acoustic stimulation is the most effective in increasing the magnitude of slow waves, likely through the activation of non-lemniscal ascending pathways to the thalamo-cortical system. In addition, we discuss how intensity and frequency of the acoustic stimuli, as well as exact timing and pattern of stimulation, affect sleep enhancement. Finally, we discuss automated algorithms that read the EEG and, in real-time, adjust the stimulation parameters in a closed-loop manner to obtain an increase in sleep slow waves and avoid undesirable arousals. In conclusion, while discussing the mechanisms that underlie the generation of sleep slow waves, we review the converging evidence showing that acoustic stimulation is safe and represents an ideal tool for slow wave sleep enhancement.

  16. Calculation of Relative Binding Free Energy in the Water-Filled Active Site of Oligopeptide-Binding Protein A.

    Science.gov (United States)

    Maurer, Manuela; de Beer, Stephanie B A; Oostenbrink, Chris

    2016-01-01

    The periplasmic oligopeptide binding protein A (OppA) represents a well-known example of water-mediated protein-ligand interactions. Here, we perform free-energy calculations for three different ligands binding to OppA, using a thermodynamic integration approach. The tripeptide ligands share a high structural similarity (all have the sequence KXK), but their experimentally-determined binding free energies differ remarkably. Thermodynamic cycles were constructed for the ligands, and simulations conducted in the bound and (freely solvated) unbound states. In the unbound state, it was observed that the difference in conformational freedom between alanine and glycine leads to a surprisingly slow convergence, despite their chemical similarity. This could be overcome by increasing the softness parameter during alchemical transformations. Discrepancies remained in the bound state however, when comparing independent simulations of the three ligands. These difficulties could be traced to a slow relaxation of the water network within the active site. Fluctuations in the number of water molecules residing in the binding cavity occur mostly on a timescale larger than the simulation time along the alchemical path. After extensive simulations, relative binding free energies that were converged to within thermal noise could be obtained, which agree well with available experimental data. PMID:27092480

  17. [Demography: can growth be slowed down?].

    Science.gov (United States)

    1990-01-01

    The UN Fund for Population Activities report on the status of world population in 1990 is particularly unsettling because it indicates that fertility is not declining as rapidly as had been predicted. The world population of some 5.3 billion is growing by 90-100 million per year. 6 years ago the growth rate appeared to be declining everywhere except in Africa and some regions of South Asia. Hopes that the world population would stabilize at around 10.2 billion by the end of the 21st century now appear unrealistic. Some countries such as the Philippines, India, and Morocco which had some success in slowing growth in the 1960s and 70s have seen a significant deceleration in the decline. Growth rates in several African countries are already 2.7% per year and increasing. It is projected that Africa's population will reach 1.581 billion by 2025. Already there are severe shortages of arable land in some overwhelmingly agricultural countries like Rwanda and Burundi, and malnutrition is widespread on the continent. Between 1979-81 and 1986- 87, cereal production declined in 25 African countries out of 43 for which the Food and Agriculture Organization has data. The urban population of developing countries is increasing at 3.6%/year. It grew from 285 million in 1950 to 1.384 billion today and is projected at 4.050 billion in 2050. Provision of water, electricity, and sanitary services will be very difficult. From 1970-88 the number of urban households without portable water increased from 138 million to 215 million. It is not merely the quality of life that is menaced by constant population growth, but also the very future of the earth as a habitat, because of the degradation of soils and forests and resulting global warming. 6-7 million hectares of agricultural land are believed to be lost to erosion each year. Deforestation is a principal cause of soil erosion. Each year more than 11 million hectares of tropical forest and forested zones are stripped, in addition to some

  18. Slow dynamics of postural sway are in the feedback loop.

    Science.gov (United States)

    Kiemel, Tim; Oie, Kelvin S; Jeka, John J

    2006-03-01

    Postural sway is considered to have two fundamental stochastic components, a slow nonoscillatory component and a faster damped-oscillatory component. The slow component has been shown to account for the majority of sway variance during quiet stance. Postural control is generally viewed as a feedback loop in which sway is detected by sensory systems and appropriate motor commands are generated to stabilize the body's orientation. Whereas the mechanistic source for the damped-oscillatory sway component is most likely feedback control of an inverted pendulum, the underlying basis for the slow component is less clear. We investigated whether the slow process was inside or outside the feedback loop by providing standing subjects with sum-of-sines visual motion. Linear stochastic models were fit to the experimental sway trajectories to determine the stochastic structure of sway as well as the transfer function from visual motion to sway. The results supported a fifth-order stochastic model, consisting of a slow process and two damped-oscillatory components. Importantly, the slow process was determined to be inside the feedback loop. This supports the hypothesis that the slow component is due to errors in state estimation because state estimation is inside the feedback loop rather than a moving reference point or an exploratory process outside the feedback loop. PMID:16192341

  19. Centrally driven slow oscillating potential of extrathoracic trachea.

    Science.gov (United States)

    Kondo, T; Kobayashi, I; Hirokawa, Y; Ohta, Y; Yamabayashi, H; Arita, H

    1993-03-01

    Spontaneous electrical activity of extrathoracic trachea was recorded along with force developed by tracheal smooth muscle and phrenic nerve activity in decerebrated, paralyzed, and artificially ventilated dogs with pneumothorax. The tracheal electrical activity exhibited slow oscillating potentials that were coupled with spontaneous phasic contraction of trachea. Both rhythmic changes were synchronous with central respiratory rhythm represented by phrenic burst, independent of the respirator's rhythm. The dominant component of the slow oscillating potentials consisted of sinusoidal waves with large amplitude that occurred shortly after cessation of phrenic burst, i.e., in the postinspiratory phase. The concomitant small change in the slow oscillating potentials began in the late inspiratory phase just before the initiation of the tracheal contraction. This phase relationship was preserved after removal of intrathoracic vagal afferents from lungs. Such slow oscillating potentials were also observed during lung collapse produced by disconnecting the tube attached to the respirator. Transection of recurrent laryngeal nerves abolished the slow oscillating potentials. These results indicate that the slow oscillating potentials of the extrathoracic trachea are generated by a physiological process associated with the central respiratory rhythm. The dominant component of the slow oscillating potentials occurs in the postinspiratory phase. PMID:8482644

  20. A Comprehensive Investigation on the Slowing Down of Cosmic Acceleration

    Science.gov (United States)

    Wang, Shuang; Hu, Yazhou; Li, Miao; Li, Nan

    2016-04-01

    Shafieloo et al. first proposed the possibility that the current cosmic acceleration (CA) is slowing down. However, this is rather counterintuitive because a slowing down CA cannot be accommodated in most mainstream cosmological models. In this work, by exploring the evolutionary trajectories of the dark energy equation of state w(z) and deceleration parameter q(z), we present a comprehensive investigation on the slowing down of CA from both the theoretical and the observational sides. For the theoretical side, we study the impact of different w(z) using six parametrization models, and then we discuss the effects of spatial curvature. For the observational side, we investigate the effects of different type Ia supernovae (SNe Ia), baryon acoustic oscillation (BAO), and cosmic microwave background (CMB) data. We find that (1) the evolution of CA is insensitive to the specific form of w(z); in contrast, a non-flat universe favors a slowing down CA more than a flat universe. (2) SNLS3 SNe Ia data sets favor a slowing down CA at a 1σ confidence level, while JLA SNe Ia samples prefer an eternal CA; in contrast, the effects of different BAO data are negligible. (3) Compared with CMB distance prior data, full CMB data favor a slowing down CA more. (4) Due to the low significance, the slowing down of CA is still a theoretical possibility that cannot be confirmed by the current observations.

  1. Slow Heavy-Particle Induced Electron Emission from Solid Surfaces

    CERN Document Server

    Burgdörfer, Joachim

    2007-01-01

    The emission of electrons from solid surfaces bombarded by slow neutral and ionized heavy particles (atoms, molecules) is reviewed both theoretically and in the light of recent experimental studies by leading groups in the field: Kinetic emission from grazing incidence of atoms and kinetic and potential emission from grazing incidence of singly and multiply charged ions on monocrystalline metal and insulator surfaces; modelling of slow electron transport in solids; emission of spin-polarized electrons by ion neutralization; electron emission from slow ion induced plasmons and excitons.

  2. Improved WKB analysis of slow-roll inflation

    International Nuclear Information System (INIS)

    We extend the WKB method for the computation of cosmological perturbations during inflation beyond leading order and provide the power spectra of scalar and tensor perturbations to second order in the slow-roll parameters. Our method does not require that the slow-roll parameters be constant. Although leading and next-to-leading results in the slow-roll parameters depend on the approximation technique used in the computation, we find that the inflationary theoretical predictions obtained may reach the accuracy required by planned observations. In two technical appendixes, we compare our technique and results with previous findings

  3. Theory of neutron slowing down in nuclear reactors

    CERN Document Server

    Ferziger, Joel H; Dunworth, J V

    2013-01-01

    The Theory of Neutron Slowing Down in Nuclear Reactors focuses on one facet of nuclear reactor design: the slowing down (or moderation) of neutrons from the high energies with which they are born in fission to the energies at which they are ultimately absorbed. In conjunction with the study of neutron moderation, calculations of reactor criticality are presented. A mathematical description of the slowing-down process is given, with particular emphasis on the problems encountered in the design of thermal reactors. This volume is comprised of four chapters and begins by considering the problems

  4. Slow light invisibility, teleportation, and other mysteries of light

    CERN Document Server

    Perkowitz, Sidney

    2011-01-01

    Slow Light is a popular treatment of today's astonishing breakthroughs in the science of light. Even though we don't understand light's quantum mysteries, we can slow it to a stop and speed it up beyond its Einsteinian speed limit, 186,000 miles/sec; use it for quantum telecommunications; teleport it; manipulate it to create invisibility; and perhaps generate hydrogen fusion power with it. All this is lucidly presented for non-scientists who wonder about teleportation, Harry Potter invisibility cloaks, and other fantastic outcomes. Slow Light shows how the real science and the fantasy inspire

  5. Ultra slow muon microscope at MUSE / J-PARC

    International Nuclear Information System (INIS)

    We report current constructing states of the Ultra Slow Muon Beam at U-line / MUSE / J-PARC, which are supported by thermal muonium (Mu, μ+e−) production with the most intense pulsed slow muon beam, laser resonant ionization, and transportation of Ultra Slow Muon Beam. A thermal Mu is produced by a hot tungsten foil in a Mu-production chamber. At the laser resonant ionization process, a thermal Mu is ionized by coherent vacuum ultraviolet radiation and coherent 355-nm radiation. The coherent radiation sources are developed at RIKEN, installed in a laser cabin, and connected via a VUV steering chamber with the Mu-production chamber.

  6. Enhanced parametric amplification in slow-light photonic crystal waveguides

    Institute of Scientific and Technical Information of China (English)

    LIU Yang; JIANG Chun

    2009-01-01

    We demonstrate both theoretically and numerically that slow light can enhance the parametric process of silicon in photonic crystal line-defect waveguides.Specifically,to get the desired gain,the pump power for a given gain medium length or the gain medium length for given pump power can be reduced by (c/vgn)2 when slow light waveguides are used,where n is the material index of conventional waveguide,vg is the group velocity of the slow light waveguide and c is the light velocity in vacuum.

  7. SHBG (Sex Hormone Binding Globulin)

    Science.gov (United States)

    ... as: Testosterone-estrogen Binding Globulin; TeBG Formal name: Sex Hormone Binding Globulin Related tests: Testosterone , Free Testosterone, ... I should know? How is it used? The sex hormone binding globulin (SHBG) test may be used ...

  8. Protein C Activity in Dogs: Adaptation of a Commercial Human Colorimetric Assay and Evaluation of Effects of Storage Time and Temperature

    Directory of Open Access Journals (Sweden)

    Michael M. Fry

    2011-01-01

    Full Text Available Objectives of this study were to adapt a commercial human protein C (PC colorimetric assay for use in dogs and to investigate effects of various storage conditions. The human assay was modified by using pooled canine plasma for calibration and by increasing the activation time. PC activity was measured in fresh canine plasma and in plasma stored under various conditions. PC activity of some stored samples was significantly different from that of fresh plasma; however, differences were small. No difference was detected in samples stored under similar conditions but analyzed in different laboratories using similar methodology. Results of this study indicate that the human colorimetric assay is suitable for canine samples if pooled canine plasma is used for calibration, that Clinical and Laboratory Standards Institute sample storage guidelines developed for testing in humans are appropriate for dogs, and that comparisons of results from laboratories using similar methodology are legitimate.

  9. Growing insights into the potential benefits and risks of activated protein C administration in sepsis: a review of preclinical and clinical studies

    Directory of Open Access Journals (Sweden)

    Laith Altaweel

    2009-09-01

    Full Text Available Laith Altaweel, Daniel Sweeney, Xizhong Cui, Amisha Barochia, Charles Natanson, Peter Q EichackerCritical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD, USAAbstract: Recombinant human activated protein C (rhAPC was developed to reduce excessive coagulant and inflammatory activity during sepsis. Basic and clinical research has suggested these pathways contribute to the pathogenesis of this lethal syndrome and are inhibited by rhAPC. Based in large part on the results of a single multicenter randomized controlled trial, rhAPC was first approved in 2001 by the US Food and Drug Administration (FDA as adjunctive therapy in septic patients with a high risk of death. This was followed closely by approval in Europe, Australia, and New Zealand. At the original FDA review of rhAPC, concerns were raised as to whether a confirmatory trial should be done before final regulatory approval because of concerns that rhAPCs bleeding risk might outweigh its potential benefit during clinical use. Since 2001, continuing basic and clinical research has further elucidated the complex role activated protein C may have in both adaptive and maladaptive responses during sepsis. Moreover, subsequent controlled trials in other types of septic patients and observational studies appear to support earlier concerns that the benefit-to-risk ratio of rhAPC may not support its clinical use. This experience has prompted additional trials presently underway, to define whether treatment with rhAPC as it was originally indicated in septic patients with persistent shock, is safe and effective. Until such trials are complete, physicians employing this agent must carefully consider which patients may be appropriate candidates for rhAPC administration.Keywords: rhAPC, treatment, sepsis

  10. Thrombomodulin Binding Selects the Catalytically Active Form of Thrombin.

    Science.gov (United States)

    Handley, Lindsey D; Treuheit, Nicholas A; Venkatesh, Varun J; Komives, Elizabeth A

    2015-11-01

    Human α-thrombin is a serine protease with dual functions. Thrombin acts as a procoagulant, cleaving fibrinogen to make the fibrin clot, but when bound to thrombomodulin (TM), it acts as an anticoagulant, cleaving protein C. A minimal TM fragment consisting of the fourth, fifth, and most of the sixth EGF-like domain (TM456m) that has been prepared has much improved solubility, thrombin binding capacity, and anticoagulant activity versus those of previous TM456 constructs. In this work, we compare backbone amide exchange of human α-thrombin in three states: apo, D-Phe-Pro-Arg-chloromethylketone (PPACK)-bound, and TM456m-bound. Beyond causing a decreased level of amide exchange at their binding sites, TM and PPACK both cause a decreased level of amide exchange in other regions including the γ-loop and the adjacent N-terminus of the heavy chain. The decreased level of amide exchange in the N-terminus of the heavy chain is consistent with the historic model of activation of serine proteases, which involves insertion of this region into the β-barrel promoting the correct conformation of the catalytic residues. Contrary to crystal structures of thrombin, hydrogen-deuterium exchange mass spectrometry results suggest that the conformation of apo-thrombin does not yet have the N-terminus of the heavy chain properly inserted for optimal catalytic activity, and that binding of TM allosterically promotes the catalytically active conformation. PMID:26468766

  11. Bacteria Experiment May Point Way to Slow Zika's Spread

    Science.gov (United States)

    ... nlm.nih.gov/medlineplus/news/fullstory_158661.html Bacteria Experiment May Point Way to Slow Zika's Spread ... 2016 (HealthDay News) -- Experiments in mosquitoes suggest that bacteria may help curb the spread of the Zika ...

  12. Are E-Cigs Slowing Teen Anti-Smoking Push?

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_159809.html Are E-Cigs Slowing Teen Anti-Smoking Push? Researchers blame ... a new study contends. "We found evidence that e-cigarettes are recruiting at least some youth who ...

  13. Second order perturbations during inflation beyond slow-roll

    International Nuclear Information System (INIS)

    We numerically calculate the evolution of second order cosmological perturbations for an inflationary scalar field without resorting to the slow-roll approximation or assuming large scales. In contrast to previous approaches we therefore use the full non-slow-roll source term for the second order Klein-Gordon equation which is valid on all scales. The numerical results are consistent with the ones obtained previously where slow-roll is a good approximation. We investigate the effect of localised features in the scalar field potential which break slow-roll for some portion of the evolution. The numerical package solving the second order Klein-Gordon equation has been released under an open source license and is available for download

  14. Recent advancement of slow light in microwave photonics applications

    OpenAIRE

    Chin, Sanghoon; Thévenaz, Luc

    2010-01-01

    A complete realization of an optically tunable true time delay, generated through the combination of a photonic RF phase shifter and a Brillouin slow light element is presented. Illustration through a dynamic microwave photonic filter is demonstrated.

  15. Bacteria Experiment May Point Way to Slow Zika's Spread

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_158661.html Bacteria Experiment May Point Way to Slow Zika's Spread Infecting ... 4, 2016 WEDNESDAY, May 4, 2016 (HealthDay News) -- Experiments in mosquitoes suggest that bacteria may help curb ...

  16. On the use of slow light for enhancing waveguide properties

    DEFF Research Database (Denmark)

    Mørk, Jesper; Nielsen, Torben Roland

    2010-01-01

    On the basis of a general analysis of waveguides containing a dispersive material, we identify conditions under which slow-light propagation may enhance the gain, absorption, or phase change. The enhancement is shown to depend on the slow-light mechanism and the translational symmetry of the wave...... waveguide. A combination of material and waveguide dispersion may strongly enhance the control of light speed, e.g., using electromagnetically induced transparency in quantum dots embedded in a photonic crystal waveguide.......On the basis of a general analysis of waveguides containing a dispersive material, we identify conditions under which slow-light propagation may enhance the gain, absorption, or phase change. The enhancement is shown to depend on the slow-light mechanism and the translational symmetry of the...

  17. Slow extraction system of the KEK-PS

    International Nuclear Information System (INIS)

    Half-integer resonance extraction at 2νH=15 has been utilized for the KEK 12-GeV Proton Synchrotron (KEK-PS). Performance of the slow extraction has been progressing recently. A slow beam extraction system was constructed for the newly build North Counter Hall. For the old East Counter Hall, the power rating of the slow extraction instruments was improved in connection with an elongation of the flat-top. The quality of the extracted beam (extraction efficiency, beam emittances and spill structure) has been systematically measured and improved by concentrated efforts. Further, a new variation of the extraction modes (deuteron beam extraction and lower energy beam extraction) has been achieved in order to contribute to the various fields of physical experiments. This report gives up-to-date descriptions of the slow extraction system of the KEK-PS. (author)

  18. Critical slowing down and error analysis in lattice QCD simulations

    Energy Technology Data Exchange (ETDEWEB)

    Schaefer, Stefan [Humboldt-Universitaet, Berlin (Germany). Inst. fuer Physik; Sommer, Rainer; Virotta, Francesco [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany). John von Neumann-Inst. fuer Computing NIC

    2010-09-15

    We study the critical slowing down towards the continuum limit of lattice QCD simulations with Hybrid Monte Carlo type algorithms. In particular for the squared topological charge we find it to be very severe with an effective dynamical critical exponent of about 5 in pure gauge theory. We also consider Wilson loops which we can demonstrate to decouple from the modes which slow down the topological charge. Quenched observables are studied and a comparison to simulations of full QCD is made. In order to deal with the slow modes in the simulation, we propose a method to incorporate the information from slow observables into the error analysis of physical observables and arrive at safer error estimates. (orig.)

  19. Slow particle multiplicity distributions for 197Au+Em interactions

    International Nuclear Information System (INIS)

    Multiplicity distributions of slow (g- and b-) particles in aurum + emulsion interactions calculated in the generalized Andersson - Otterlund - Stenlund (AOS) model are presented. 3 bumps in distributions are observed. 6 refs.; 2 figs.; 1 tab

  20. Periodic slow slip triggers megathrust zone earthquakes in northeastern Japan.

    Science.gov (United States)

    Uchida, Naoki; Iinuma, Takeshi; Nadeau, Robert M; Bürgmann, Roland; Hino, Ryota

    2016-01-29

    Both aseismic and seismic slip accommodate relative motion across partially coupled plate-boundary faults. In northeastern Japan, aseismic slip occurs in the form of decelerating afterslip after large interplate earthquakes and as relatively steady slip on uncoupled areas of the subduction thrust. Here we report on a previously unrecognized quasi-periodic slow-slip behavior that is widespread in the megathrust zone. The repeat intervals of the slow slip range from 1 to 6 years and often coincide with or precede clusters of large [magnitude (M) ≥ 5] earthquakes, including the 2011 M 9 Tohoku-oki earthquake. These results suggest that inherently periodic slow-slip events result in periodic stress perturbations and modulate the occurrence time of larger earthquakes. The periodicity in the slow-slip rate has the potential to help refine time-dependent earthquake forecasts. PMID:26823425

  1. Critical slowing down and error analysis in lattice QCD simulations

    International Nuclear Information System (INIS)

    We study the critical slowing down towards the continuum limit of lattice QCD simulations with Hybrid Monte Carlo type algorithms. In particular for the squared topological charge we find it to be very severe with an effective dynamical critical exponent of about 5 in pure gauge theory. We also consider Wilson loops which we can demonstrate to decouple from the modes which slow down the topological charge. Quenched observables are studied and a comparison to simulations of full QCD is made. In order to deal with the slow modes in the simulation, we propose a method to incorporate the information from slow observables into the error analysis of physical observables and arrive at safer error estimates. (orig.)

  2. Thyroxine binding to serum thyronine-binding globulin in thyroidectomized adult and normal neonatal rats

    International Nuclear Information System (INIS)

    The amount of tracer [125I]T4 bound to serum thyronine-binding globulin (TBG) was measured by polyacrylamide gel electrophoresis in adult thyroidectomized (TX) rats and normal 1-day to 4-week-old rat puts. Thyroidectomy was associated with the appearance of significant amounts of [125I]T4 binding to serum TBG in lean rats, but not in obese Zucker rats. Treatment of the TX rats in vivo with replacement doses of T4 prevented this increase in TBG binding, but enrichment of serum from TX rats with T4 did not. Significant amounts of tracer [125I]T4 binding to TBG was present in serum from 1- to 3-week-old normal rat pups, but not in 1-day- or 4-week-old pups. There were significantly higher levels of TBG binding of [125I]T4 in serum from 2-week-old rat pups raised in litters of 16 pups compared to those raised in litters of 4 pups. All manipulations that result in the appearance of TBG in rat serum also result in either weight loss or a slowing in the rate of growth, suggesting that the appearance of TBG in rat serum has a nutritional component. This possibility is further supported by the observations that increases in TBG binding of [125I]T4 are not found in obese Zucker rats fed a low protein-high carbohydrate diet for 14 days or fasted for 7 days, or after thyroidectomy, perhaps owing to the large stores of fuel in the obese rat

  3. Exploring carrier dynamics in semiconductors for slow light

    DEFF Research Database (Denmark)

    Mørk, Jesper; Xue, Weiqi; Chen, Yaohui;

    2009-01-01

    We give an overview of recent results on slow and fast light in active semiconductor waveguides. The cases of coherent population oscillations as well as electromagnetically induced transparency are covered, emphasizing the physics and fundamental limitations.......We give an overview of recent results on slow and fast light in active semiconductor waveguides. The cases of coherent population oscillations as well as electromagnetically induced transparency are covered, emphasizing the physics and fundamental limitations....

  4. Neutron slowing-down time in finite water systems

    International Nuclear Information System (INIS)

    The influence of the size of a moderator system on the neutron slowing-down time has been investigated. The experimental part of the study was performed on six cubes of water with side lengths from 8 to 30 cm. Neutrons generated in pulses of about 1 ns width were slowed down from 14 MeV to 1.457 eV. The detection method used was based on registration of gamma radiation from the main capture resonance of indium. The most probable slowing-down times were found to be 778 +- 23 ns and 898 +- 25 ns for the smallest and for the largest cubes, respectively. The corresponding mean slowing-down times were 1205 +- 42 ns and 1311 +- 42 ns. In a separate measurement series the space dependence of the slowing-down time close to the source was studied. These experiments were supplemented by a theoretical calculation which gave an indication of the space dependence of the slowingdown time in finite systems. The experimental results were compared to the slowing-down times obtained from various theoretical approaches and from Monte Carlo calculations. All the methods show a decrease of the slowing-down time with decreasing size of the moderator. This effect was least pronounced in the experimental results, which can be explained by the fact the measurements are spatially dependent. The agreement between the Monte Carlo results and those obtained using the diffusion approximation or the age-diffusion theory is surprisingly good, especially for large systems. The P1 approximation, on the other hand, leads to an overestimation of the effect of the finite size on the slowing-down time. (author)

  5. Multisteps Global Kinetic Analysis of MSW Slow Pyrolysis

    OpenAIRE

    Dwi Aries Himawanto

    2013-01-01

    The goal of this research is to find relationships between single components slow pyrolysis characteristics and mixed component slow pyrolysis characteristics of segregated municipal solid wastes (MSW). The material of this research consists of organic wastes (bamboo wastes and banana leaves wastes) and inorganic wastes (styrofoam wastes and snack wrapping wastes. The materials which used to study were the unprosessing waste. The samples were collected, dried and crushed until passing 20 mesh...

  6. Production of slow-released nitrogen fertilizer from urine

    OpenAIRE

    Ito, Ryusei; Takahashi, Eri; Funamizu, Naoyuki

    2013-01-01

    Human excreta, especially urine is rich in nitrogen that can be utilized for agricultural purposes, while the slow-release fertilizer allows effective utilization of nutrients in agricultural production. The direct formation of slow-release fertilizer - methylene urea - from urine was being proposed in this study. The experiments were tried to prove formation of methylene urea from human urine, and to investigate the effect of pH and salt concentration on the reaction rate. The synthetic urin...

  7. Slow-light enhancement of Beer-Lambert-Bouguer absorption

    DEFF Research Database (Denmark)

    Mortensen, Asger; Xiao, Sanshui

    2007-01-01

    We theoretically show how slow light in an optofluidic environment facilitates enhanced light-matter interactions, by orders of magnitude. The proposed concept provides strong opportunities for improving existing miniaturized chemical absorbance cells for Beer-Lambert-Bouguer absorption measureme......We theoretically show how slow light in an optofluidic environment facilitates enhanced light-matter interactions, by orders of magnitude. The proposed concept provides strong opportunities for improving existing miniaturized chemical absorbance cells for Beer-Lambert-Bouguer absorption...

  8. Slow and fast light in semiconductor structures: physics and applications

    DEFF Research Database (Denmark)

    Mørk, Jesper; Nielsen, Torben Roland; Xue, Weiqi;

    We discuss the physics and applications of slow light in semiconductor waveguides. In particular we introduce methods for enhancing the degree of light speed control considering both electromagnetically induced transparency as well as coherent population oscillations.......We discuss the physics and applications of slow light in semiconductor waveguides. In particular we introduce methods for enhancing the degree of light speed control considering both electromagnetically induced transparency as well as coherent population oscillations....

  9. Slow Motion and Zoom in HD Digital Videos Using Fractals

    OpenAIRE

    Maurizio Murroni; Cristian Perra; Giusto, Daniele D.

    2009-01-01

    Slow motion replay and spatial zooming are special effects used in digital video rendering. At present, most techniques to perform digital spatial zoom and slow motion are based on interpolation for both enlarging the size of the original pictures and generating additional intermediate frames. Mainly, interpolation is done either by linear or cubic spline functions or by motion estimation/compensation which both can be applied pixel by pixel, or by partitioning frames into blocks. Purpose of ...

  10. Slow Light Devices and Their Applications to Microwaves and Photonics

    OpenAIRE

    Santagiustina, M.; Eisenstein, G.; Thévenaz, Luc; Capmany, J.; Mork, J.; Reithmaier, J. P.; Rossi, A.; Sales, S; Yvind, K.; Combrié, S.; Bourderionnet, J

    2012-01-01

    Recently developed, highly effective technologies enabling slow light propagation as a tunable feature in photonic devices, are reviewed. Several applications in ICT are also demonstrated. Controlling the group velocity of light offers a broadband solution to a necessary functionality in microwave and millimeter wave systems: a tunable time-delay/phase-shift line. Moreover, slow light can highly enhance the nonlinearity, thus opening the way to on chip, nonlinear photonics.

  11. Development of slow pyrolysis business operations in Finland - Hidaspyro

    Energy Technology Data Exchange (ETDEWEB)

    Fagernas, L. [VTT Technical Research Centre of Finland, Espoo (Finland)], email: leena.fagernas@vtt.fi

    2012-07-01

    Birch distillate, a by-product in slow pyrolysis process of charcoal production, was found to be a promising source for biological pesticides. However, product commercialization was problematic, for EU registration is costly, and composition, active ingredients and ecotoxicological properties were not known. In addition, constant quality and process optimisation were needed. More collaboration between SMEs and research institutes was required. The primary aim was to support and develop slow pyrolysis business operations of SMEs in Finland by generating knowledge that was needed.

  12. The rediscovery of slowness: exploring the timing of cognition

    OpenAIRE

    Morten L Kringelbach; McIntosh, Anthony R.; Ritter, Petra; Jirsa, Viktor K.; Deco, Gustavo

    2015-01-01

    Slowness of thought is not necessarily a handicap but could be a signature of optimal brain function. Emerging evidence shows that neuroanatomical and dynamical constraints of the human brain shape its functionality in optimal ways, characterized by slowness during task-based cognition in the context of spontaneous resting-state activity. This activity can be described mechanistically by whole-brain computational modeling that relates directly to optimality in the context of theories arguing ...

  13. Slow shock formation and temperature anisotropy in collisionless magnetic reconnection

    Science.gov (United States)

    Higashimori, K.; Hoshino, M.

    2011-12-01

    We perform a two-dimensional simulation by using an electromagnetic hybrid code to study the formation of slow-mode shocks in collisionless magnetic reconnection in low beta plasmas, and we argue that one of important agents of the formation of slow shocks is the ion temperature anisotropy enhanced at the shock downstream region. As magnetic reconnection develops, it is known that the parallel temperature along the magnetic field becomes large in association with the anisotropic PSBL ion beams, and this temperature anisotropy has a tendency to suppress the formation of slow shock. Although preceding studies on magnetic reconnection with kinetic codes have shown such ion temperature anisotropy along the reconnection layer, the direct relation between formation of slow shocks and the ion temperature anisotropy has not been investigated. Based on our simulation result, we found that the slow shock formation is suppressed due to the large temperature anisotropy near the X-type region, but the downstream ion temperature anisotropy relaxes with increasing the distance from the magnetic neutral point. As a result, two pairs of current structures, which are the strong evidence of dissipation of magnetic field in slow shocks, are formed at the distance |x| > 115 λ i from the neutral point.

  14. A Common Structural Component for β-Subunit Mediated Modulation of Slow Inactivation in Different KV Channels

    Directory of Open Access Journals (Sweden)

    Nathalie Strutz-Seebohm

    2013-06-01

    Full Text Available Background/Aims: Potassium channels are tetrameric proteins providing potassium selective passage through lipid embedded proteinaceous pores with highest fidelity. The selectivity results from binding to discrete potassium binding sites and stabilization of a hydrated potassium ion in a central internal cavity. The four potassium binding sites, generated by the conserved TTxGYGD signature sequence are formed by the backbone carbonyls of the amino acids TXGYG. Residues KV1.5-Val481, KV4.3-Leu368 and KV7.1- Ile 313 represent the amino acids in the X position of the respective channels. Methods: Here, we study the impact of these residues on ion selectivity, permeation and inactivation kinetics as well as the modulation by β-subunits using site-specific mutagenesis, electrophysiological analyses and molecular dynamics simulations. Results: We identify this position as key in modulation of slow inactivation by structurally dissimilar β-subunits in different KV channels. Conclusion: We propose a model in which structural changes accompanying activation and β-subunit modulation allosterically constrain the backbone carbonyl oxygen atoms via the side chain of the respective X-residue in the signature sequence to reduce conductance during slow inactivation.

  15. HLA Alleles Associated with Slow Progression to AIDS Truly Prefer to Present HIV-1 p24

    DEFF Research Database (Denmark)

    Borghans, J. A.; Molgaard, A.; Boer, R. J. de;

    2007-01-01

    BACKGROUND: The mechanism behind the association between human leukocyte antigen (HLA) molecules and the rate of HIV-1 disease progression is still poorly understood. Recent data suggest that "protective" HLA molecules, i.e. those associated with a low HIV-1 viral load and relatively slow disease...... effect, we predicted HIV-1 epitopes from the whole genome of HIV-1, and found that protective HLA alleles have a true preference for the p24 Gag protein, while non-protective HLA alleles preferentially target HIV-1 Nef. In line with this, we found a significant negative correlation between the predicted...... affinity of the best-binding p24 epitopes and the relative hazard of HIV-1 disease progression for a large number of HLA molecules. When the epitopes targeted by protective HLA alleles were mapped to the known p24 structure, we found that mutations in these epitopes are likely to disturb the p24 dimer...

  16. HLA alleles associated with slow progression to AIDS truly prefer to present HIV-1 p24

    DEFF Research Database (Denmark)

    Borghans, José A M; Mølgaard, Anne; de Boer, Rob J;

    2007-01-01

    BACKGROUND: The mechanism behind the association between human leukocyte antigen (HLA) molecules and the rate of HIV-1 disease progression is still poorly understood. Recent data suggest that "protective" HLA molecules, i.e. those associated with a low HIV-1 viral load and relatively slow disease...... effect, we predicted HIV-1 epitopes from the whole genome of HIV-1, and found that protective HLA alleles have a true preference for the p24 Gag protein, while non-protective HLA alleles preferentially target HIV-1 Nef. In line with this, we found a significant negative correlation between the predicted...... affinity of the best-binding p24 epitopes and the relative hazard of HIV-1 disease progression for a large number of HLA molecules. When the epitopes targeted by protective HLA alleles were mapped to the known p24 structure, we found that mutations in these epitopes are likely to disturb the p24 dimer...

  17. Principles of Slow Fashion Application in Clothing Collection Creation

    Directory of Open Access Journals (Sweden)

    Agnė Antanavičiūtė

    2015-10-01

    Full Text Available Today we can clearly see the damage which is caused by fast fashion production and mass consumption. Therefore, a relevant issue is how to reduce consumption, waste, and threat to the environment and human health. Research into the slow fashion designers approach towards eco-friendly and slow fashion products shows that it is necessary to spread ideas of slow fashion widely and teach users about ecologically friendly clothing. Therefore, this paper analyses theoretical and practical slow fashion principles applied by slow fashion designers; according to this, the collection ‘Just Share’ was created. The aim of the collection is to spread ideas of slow fashion and adapt them in specific technical projects dealing with the problems of use and production waste minimisation and creating sustainable, easily recyclable, environmentally friendly garments. Products for reducing consumption are developed based on the idea of sharing clothing. Therefore, garments are one size and suitable for different types of figures of men and women.  Clothing design is inspired by folding, so models have various pleats, unfolds allowing minimal transformation of the garment, which gives the product its individuality and extends time of wearing. Models are designed with a minimal amount of accessories and minimum division lines, maintaining the uniformity of materials and uncomplicated sewing technology. In this way, out of wear garments can be easily remade. Original constructions of models are based on the ‘zero waste’ principle. This method reduces waste generation. So this research was prepared using the principles of slow fashion, which has a potential to reduce excessive consumption and stop growth of textile waste.DOI: http://dx.doi.org/10.5755/j01.erem.71.2.12392

  18. Inhibition of selectin binding

    Energy Technology Data Exchange (ETDEWEB)

    Nagy, Jon O. (Rodeo, CA); Spevak, Wayne R. (Albany, CA); Dasgupta, Falguni (New Delhi, IN); Bertozzi, Caroline (Albany, CA)

    2001-10-09

    This invention provides compositions for inhibiting the binding between two cells, one expressing P- or L-selectin on the surface and the other expressing the corresponding ligand. A covalently crosslinked lipid composition is prepared having saccharides and acidic group on separate lipids. The composition is then interposed between the cells so as to inhibit binding. Inhibition can be achieved at an effective oligosaccharide concentration as low as 10.sup.6 fold below that of the free saccharide. Since selectins are involved in recruiting cells to sites of injury, these composition scan be used to palliate certain inflammatory and immunological conditions.

  19. Inhibition of selectin binding

    Energy Technology Data Exchange (ETDEWEB)

    Nagy, J.O.; Spevak, W.R.; Dasgupta, F.; Bertozzi, C.

    1999-10-05

    This invention provides a system for inhibiting the binding between two cells, one expressing P- or L-selectin on the surface and the other expressing the corresponding ligand. A covalently crosslinked lipid composition is prepared having saccharides and acidic group on separate lipids. The composition is then interposed between the cells so as to inhibit binding. Inhibition can be achieved at an effective oligosaccharide concentration as low as 10{sup 6} fold below that of the free saccharide. Since selectins are involved in recruiting cells to sites of injury, this system can be used to palliate certain inflammatory and immunological conditions.

  20. Inhibition of selectin binding

    Energy Technology Data Exchange (ETDEWEB)

    Nagy, Jon O. (Rodeo, CA); Spevak, Wayne R. (Albany, CA); Dasgupta, Falguni (New Delhi, IN); Bertozzi, Caroline (Albany, CA)

    1999-01-01

    This invention provides compositions for inhibiting the binding between two cells, one expressing P- or L-selectin on the surface and the other expressing the corresponding ligand. A covalently crosslinked lipid composition is prepared having saccharides and acidic group on separate lipids. The composition is then interposed between the cells so as to inhibit binding. Inhibition can be achieved at an effective oligosaccharide concentration as low as 10.sup.6 fold below that of the free saccharide. Since selectins are involved in recruiting cells to sites of injury, these composition scan be used to palliate certain inflammatory and immunological conditions.

  1. Inhibition of selectin binding

    Energy Technology Data Exchange (ETDEWEB)

    Nagy, J.O.; Spevak, W.R.; Dasgupta, F.; Bertozzi, C.

    1999-11-16

    This invention provides compositions for inhibiting the binding between two cells, one expressing P- or L-selectin on the surface and the other expressing the corresponding ligand. A covalently crosslinked lipid composition is prepared having saccharides and acidic group on separate lipids. The composition is then interposed between the cells so as to inhibit binding. Inhibition can be achieved at an effective oligosaccharide concentration as low as 10{sup 6} fold below that of the free saccharide. Since selectins are involved in recruiting cells to sites of injury, these composition scan be used to palliate certain inflammatory and immunological conditions.

  2. Inhibition of selectin binding

    Energy Technology Data Exchange (ETDEWEB)

    Nagy, Jon O. (Rodeo, CA); Spevak, Wayne R. (Albany, CA); Dasgupta, Falguni (New Delhi, IN); Bertozzi, Carolyn (Albany, CA)

    1999-10-05

    This invention provides a system for inhibiting the binding between two cells, one expressing P- or L-selectin on the surface and the other expressing the corresponding ligand. A covalently crosslinked lipid composition is prepared having saccharides and acidic group on separate lipids. The composition is then interposed between the cells so as to inhibit binding. Inhibition can be achieved at an effective oligosaccharide concentration as low as 10.sup.6 fold below that of the free saccharide. Since selectins are involved in recruiting cells to sites of injury, this system can be used to palliate certain inflammatory and immunological conditions.

  3. MANAGING TIGHT BINDING RECEPTORS FOR NEW SPEARATIONS TECHNOLOGIES

    Energy Technology Data Exchange (ETDEWEB)

    DARYLE H BUSCH RICHARD S GIVENS

    2004-12-10

    Much of the earth's pollution involves compounds of the metallic elements, including actinides, strontium, cesium, technetium, and RCRA metals. Metal ions bind to molecules called ligands, which are the molecular tools that can manipulate the metal ions under most conditions. This DOE-EMSP sponsored program strives (1) to provide the foundations for using the most powerful ligands in transformational separations technologies and (2) to produce seminal examples of their applications to separations appropriate to the DOE EM mission. These ultra tight-binding ligands can capture metal ions in the most competitive of circumstances (from mineralized sites, lesser ligands, and even extremely dilute solutions), but they react so slowly that they are useless in traditional separations methodologies. Two attacks on this problem are underway. The first accommodates to the challenging molecular lethargy by developing a seminal slow separations methodology termed the soil poultice. The second designs ligands that are only tight-binding while wrapped around the targeted metal ion, but can be put in place by switch-binding and removed by switch-release. We envision a kind of molecular switching process to accelerate the union between metal ion and tight-binding ligand. Molecular switching processes are suggested for overcoming the slow natural equilibration rate with which ultra tight-binding ligands combine with metal ions. Ligands that bind relatively weakly combine with metal ions rapidly, so the trick is to convert a ligand from a weak, rapidly binding species to a powerful, slow releasing ligand--during the binding of the ligand to the metal ion. Such switch-binding ligands must react with themselves, and the reaction must take place under the influence of the metal ion. For example, our generation 1 ligands showed that a well-designed linear ligand with ends that readily combine, forms a cyclic molecule when it wraps around a metal ion. Our generation 2 ligands are

  4. CCAAT/enhancer binding proteins alpha and epsilon cooperate with all-trans retinoic acid in therapy but differ in their antileukemic activities

    OpenAIRE

    Lee, Young-jin; Jones, Letetia C.; Timchenko, Nikolai A.; Perrotti, Danilo; Tenen, Daniel G; Kogan, Scott C.

    2006-01-01

    CCAAT/enhancer binding proteins (C/EBPs) play critical roles in myelopoiesis. Dysregulation of these proteins likely contributes to the pathogenesis of myeloid disorders characterized by a block in granulopoiesis. In one such disease, acute promyelocytic leukemia (APL), a promyelocytic leukemia–retinoic acid receptor α (PML-RARα) fusion protein is expressed as a result of a t(15;17) chromosomal translocation. Treatment of PML-RARα leukemic cells with all-trans retinoic acid (ATRA) causes them...

  5. Ligand photo-isomerization triggers conformational changes in iGluR2 ligand binding domain.

    Directory of Open Access Journals (Sweden)

    Tino Wolter

    Full Text Available Neurological glutamate receptors bind a variety of artificial ligands, both agonistic and antagonistic, in addition to glutamate. Studying their small molecule binding properties increases our understanding of the central nervous system and a variety of associated pathologies. The large, oligomeric multidomain membrane protein contains a large and flexible ligand binding domains which undergoes large conformational changes upon binding different ligands. A recent application of glutamate receptors is their activation or inhibition via photo-switchable ligands, making them key systems in the emerging field of optochemical genetics. In this work, we present a theoretical study on the binding mode and complex stability of a novel photo-switchable ligand, ATA-3, which reversibly binds to glutamate receptors ligand binding domains (LBDs. We propose two possible binding modes for this ligand based on flexible ligand docking calculations and show one of them to be analogues to the binding mode of a similar ligand, 2-BnTetAMPA. In long MD simulations, it was observed that transitions between both binding poses involve breaking and reforming the T686-E402 protein hydrogen bond. Simulating the ligand photo-isomerization process shows that the two possible configurations of the ligand azo-group have markedly different complex stabilities and equilibrium binding modes. A strong but slow protein response is observed after ligand configuration changes. This provides a microscopic foundation for the observed difference in ligand activity upon light-switching.

  6. Formalizing the slow-roll approximation in inflation

    Science.gov (United States)

    Liddle, Andrew R.; Parsons, Paul; Barrow, John D.

    1994-12-01

    The meaning of the inflationary slow-roll approximation is formalized. Comparisons are made between an approach based on the Hamilton-Jacobi equations, governing the evolution of the Hubble parameter, and the usual scenario based on the evolution of the potential energy density. The vital role of the inflationary attractor solution is emphasized, and some of its properties described. We propose a new measure of inflation, based upon contraction of the comoving Hubble length as opposed to the usual e-foldings of physical expansion, and derive relevant formulas. We introduce an infinite hierarchy of slow-roll parameters, and show that only a finite number of them are required to produce results to a given order. The extension of the slow-roll approximation into an analytic slow-roll expansion, converging on the exact solution, is provided. Its role in calculations of inflationary dynamics is discussed. We explore rational approximants as a method of extending the range of convergence of the slow-roll expansion up to, and beyond, the end of inflation.

  7. A taste of ethical consumption at a slow food festival.

    Science.gov (United States)

    Williams, Lauren T; Germov, John; Fuller, Sascha; Freij, Maria

    2015-08-01

    This paper examines the motives and experiences of attendees at a Slow Food festival to gain an understanding of how people engage with ethical consumer projects. Slow Food is a global social movement aimed at promoting food that is regionally, ethically, and sustainably produced, and convivially consumed. The movement uses culinary tourist events, such as food festivals and farmers' markets, to promote its philosophy and attract new members. There have been no empirical studies of ethical consumption using a Slow Food event as a case study. This study uses an ethnographic approach and a framework of virtue ethics to explore the views of people attending a major Slow Food festival in the city of Melbourne, Australia. Semi-structured interviews were conducted in situ with 33 participants (19 consumers and 14 stallholders) to discover their rationales for attending the festival, and their perspectives on ethical consumption. Transcripts were coded and thematically analysed, resulting in three themes reflecting varying degrees of public virtues (altruistic motivations) and private virtues (personal wellbeing): the quest for virtuous lifestyles through ethical consumption, the importance of co-production, and the challenges of putting ethical consumer projects like Slow Food into daily practice. The findings reveal the manner in which virtue ethics affects foodways and highlights the contingent and challenging nature of practising ethical eating. PMID:25934088

  8. Differentiation of fast and slow muscle fibers by bioimpedance

    Science.gov (United States)

    Moreno, M.-V.; Khider, N.; Ribbe, E.; Damez, J.-L.

    2010-04-01

    The differentiation of fast and slow muscle fibers in vivo still requires constraining equipment (ergometer, biopsy ...) and invasive techniques. These fibers conduct the electrical current differently. Therefore the aim of this study is to see if it is possible to differentiate quickly, by bioimpedance, fast and slow fibers, and firstly muscles which are typical composed by slow or fast fibers. To do this, we used a multifrequency impedancemeter Z-Metrix® (BioparHom© Company, France). We collected the electrical characteristics (Longitudinal and Transversal, from 1 to 1000 kHz) for a population of 20 rats aged 70 days, on Soleus muscles (composed principally of slow fibers) and Extensor Digitroum Longus (EDL) muscles (composed principally of fast fibers). We compared the means of alpha (L/T), R (L/T) and X (L/T) with Wilcoxon tests. We obtained non significant differences between electrical data obtained on EDL and Soleus muscles, but we could see differences on graphics representation and with the example of one rat. Therefore, we can assume that differentiation, by bioimpedance, of muscles typed slow and fast fibers, could be possible.

  9. STUDY ON GASTROINTESTINAL MOTILITY IN SLOW TRANSIT CONSTIPATION

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To investigate motor activity of gastrointestinal tract in patients with slow transit constipation(STC). Methods 42 patients with STC and 20 healthy controls were included in the study. Each subject underwent colonic transit test, gastric emptying, orocecal transit time, electromyography and anorectal manometry. Results According to transit index, 42 STC patients were divided into 3 types: ①0.5slow rectosigmoid transit 15 cases; ②TI=0.5, colorectal stasis 10 cases; ③0slow colonic transit 17 cases. Gastric emptying rate at the fourth hour was decreased in STC patients than in controls (P<0.05). The mean orocaecal transit time was significantly delayed in the patients (P<0.05). Paradoxical anal sphincter contraction with defecation effort was higher prevalent in patients with slow rectosigmoid transit and colorectal stasis than patients with slow colonic transit(P<0.01,respectively). Minimum relaxation volume and maximal rectal tolerable volume were significantly increased in STC patients (P<0.05,respectively). Conclusion STC displayed colonic abnormality, and/or pelvic floor dysfunction. In addition, it showed motor abnormalities of upper gut, might be part of a pan-enteric motor disorders.

  10. Sequential memory: Binding dynamics

    Science.gov (United States)

    Afraimovich, Valentin; Gong, Xue; Rabinovich, Mikhail

    2015-10-01

    Temporal order memories are critical for everyday animal and human functioning. Experiments and our own experience show that the binding or association of various features of an event together and the maintaining of multimodality events in sequential order are the key components of any sequential memories—episodic, semantic, working, etc. We study a robustness of binding sequential dynamics based on our previously introduced model in the form of generalized Lotka-Volterra equations. In the phase space of the model, there exists a multi-dimensional binding heteroclinic network consisting of saddle equilibrium points and heteroclinic trajectories joining them. We prove here the robustness of the binding sequential dynamics, i.e., the feasibility phenomenon for coupled heteroclinic networks: for each collection of successive heteroclinic trajectories inside the unified networks, there is an open set of initial points such that the trajectory going through each of them follows the prescribed collection staying in a small neighborhood of it. We show also that the symbolic complexity function of the system restricted to this neighborhood is a polynomial of degree L - 1, where L is the number of modalities.

  11. Kinetics characterization of c-Src binding to lipid membranes: Switching from labile to persistent binding.

    Science.gov (United States)

    Le Roux, Anabel-Lise; Busquets, Maria Antònia; Sagués, Francesc; Pons, Miquel

    2016-02-01

    Cell signaling by the c-Src proto-oncogen requires the attachment of the protein to the inner side of the plasma membrane through the myristoylated N-terminal region, known as the SH4 domain. Additional binding regions of lower affinity are located in the neighbor intrinsically disordered Unique domain and the structured SH3 domain. Here we present a surface plasmon resonance study of the binding of a myristoylated protein including the SH4, Unique and SH3 domains of c-Src to immobilized liposomes. Two distinct binding processes were observed: a fast and a slow one. The second process lead to a persistently bound form (PB) with a slower binding and a much slower dissociation rate than the first one. The association and dissociation of the PB form could be detected using an anti-SH4 antibody. The kinetic analysis revealed that binding of the PB form follows a second order rate law suggesting that it involves the formation of c-Src dimers on the membrane surface. A kinetically equivalent PB form is observed in a myristoylated peptide containing only the SH4 domain but not in a construct including the three domains but with a 12-carbon lauroyl substituent instead of the 14-carbon myristoyl group. The PB form is observed with neutral lipids but its population increases when the immobilized liposomes contain negatively charged lipids. We suggest that the PB form may represent the active signaling form of c-Src while the labile form provides the capacity for fast 2D search of the target signaling site on the membrane surface. PMID:26638178

  12. Slow fragmentation of hydrocarbons after ultrafast laser interaction

    CERN Document Server

    Larimian, Seyedreza; Lötstedt, Erik; Szidarovszky, Tamás; Maurer, Raffael; Roither, Stefan; Schöffler, Markus; Kartashov, Daniil; Baltuška, Andrius; Yamanouchi, Kaoru; Kitzler, Markus; Xie, Xinhua

    2015-01-01

    We experimentally and theoretically investigated the deprotonation process on nanosecond to microsecond timescale in ethylene and acetylene molecules, following their double ionization by a strong femtosecond laser field. In our experiments we utilized coincidence detection with the reaction microscope technique, and found that both the mean lifetime of the ethylene dication leading to the "slow" deprotonation and the relative channel strength of the slow deprotonation compared to the fast one have no evident dependence on the laser pulse duration and the laser peak intensity. Furthermore, quantum chemical simulations suggest that such slow fragmentation originates from the tunneling of near-dissociation-threshold vibrational states through a dissociation barrier on an electronic dication state. Such vibrational states can be populated through strong field double ionization induced vibrational excitation on an electronically excited state in the case of ethylene, and through intersystem processes from electro...

  13. Slow dynamics in the nonlinear elastic response of Berea sandstone

    Science.gov (United States)

    Ten Cate, James A.; Shankland, Thomas J.

    A typical resonance curve—measured acceleration versus drive frequency—made on a thin bar of rock shows peak bending with a softening (nonlinear) modulus as drive levels are increased. The shapes of these nonlinear resonance curves were found in earlier work to depend somewhat on sweep rate; these “slow dynamics” are now examined and quantified. We have measured slow dynamics in a 0.3 m long, 50 mm diameter bar of Berea sandstone under ambient conditions. Peak strain levels during the experiments ranged from 10-11 to 10-5 at driving frequencies near 4 kHz, the fundamental longitudinal resonance frequency of the bar. Slow dynamics begin to manifest themselves at strain amplitudes above 10-6 at ambient conditions and at the onset of nonlinear peak bending. Strains above this value condition the rock, altering its response for minutes to hours after the drive has been turned off.

  14. Forward Modelling of Standing Slow Modes in Flaring Coronal Loops

    CERN Document Server

    Yuan, D; Banerjee, D; Antolin, P

    2015-01-01

    Standing slow mode waves in hot flaring loops are exclusively observed in spectrometers and are used to diagnose the magnetic field strength and temperature of the loop structure. Due to the lack of spatial information, the longitudinal mode cannot be effectively identified. In this study, we simulate standing slow mode waves in flaring loops and compare the synthesized line emission properties with SUMER spectrographic and SDO/AIA imaging observations. We find that the emission intensity and line width oscillations are a quarter period out of phase with Doppler shift velocity both in time and spatial domain, which can be used to identify a standing slow mode wave from spectroscopic observations. However, the longitudinal overtones could be only measured with the assistance of imagers. We find emission intensity asymmetry in the positive and negative modulations, this is because the contribution function pertaining to the atomic emission process responds differently to positive and negative temperature variat...

  15. Hydrodynamical behavior of symmetric exclusion with slow bonds

    CERN Document Server

    Franco, Tertuliano; Neumann, Adriana

    2010-01-01

    We consider the exclusion process in the one-dimensional discrete torus with $N$ points, where all the bonds have conductance one, except a finite number of slow bonds, with conductance $N^{-\\beta}$, with $\\beta\\in[0,\\infty)$. We prove that the time evolution of the empirical density of particles, in the diffusive scaling, has a distinct behavior according to the range of the parameter $\\beta$. If $\\beta\\in [0,1)$, the hydrodynamic limit is given by the usual heat equation. If $\\beta=1$, it is given by a parabolic equation involving an operator $\\frac{d}{dx}\\frac{d}{dW}$, where $W$ is the Lebesgue measure on the torus plus the sum of the Dirac measure supported on each macroscopic point related to the slow bond. If $\\beta\\in(1,\\infty)$, it is given by the heat equation with Neumann's boundary conditions, meaning no passage through the slow bonds in the continuum.

  16. A comprehensive investigation on the slowing down of cosmic acceleration

    CERN Document Server

    Hu, Yazhou; Li, Nan; Wang, Shuang

    2015-01-01

    In~\\citep{Shafieloo2009}, Shafieloo, Sanhi and Starobinsky firstly proposed the possibility that the current cosmic acceleration (CA) is slowing down. This is rather counterintuitive, because a slowing down CA cannot be accommodated in almost all the mainstream cosmological models. In this work, by exploring the evolutionary trajectories of dark energy equation of state $w(z)$ and deceleration parameter $q(z)$, we present a comprehensive investigation on the slowing down of CA from both the theoretical and the observational sides. For the theoretical side, we study the impacts of different $w(z)$ by using six parametrization models, and then discuss the effects of spatial curvature. For the observational side, we investigate the effects of different type Ia supernovae (SNe Ia), different baryon acoustic oscillation (BAO), and different cosmic microwave background (CMB) data, respectively. We find that the evolution of CA are insensitive to the specific form of $w(z)$; in contrast, a non-flat Universe more fav...

  17. The slow and fast pyrolysis of cherry seed.

    Science.gov (United States)

    Duman, Gozde; Okutucu, Cagdas; Ucar, Suat; Stahl, Ralph; Yanik, Jale

    2011-01-01

    The slow and fast pyrolysis of cherry seeds (CWS) and cherry seeds shells (CSS) was studied in fixed-bed and fluidized bed reactors at different pyrolysis temperatures. The effects of reactor type and temperature on the yields and composition of products were investigated. In the case of fast pyrolysis, the maximum bio-oil yield was found to be about 44 wt% at pyrolysis temperature of 500 °C for both CWS and CSS, whereas the bio yields were of 21 and 15 wt% obtained at 500 °C from slow pyrolysis of CWS and CSS, respectively. Both temperature and reactor type affected the composition of bio-oils. The results showed that bio-oils obtained from slow pyrolysis of CWS and CSS can be used as a fuel for combustion systems in industry and the bio-oil produced from fast pyrolysis can be evaluated as a chemical feedstock. PMID:20801019

  18. Slow light with electromagnetically induced transparency in optical fibre

    Science.gov (United States)

    Muhamad Hatta, Agus; Kamli, Ali A.; Al-Hagan, Ola A.; Moiseev, Sergey A.

    2015-08-01

    Slow light with electromagnetically induced transparency (EIT) in the core of optical fibre containing three-level atoms is investigated. The guided modes are treated in the weakly guiding approximation which renders the analysis into a manageable form. The transparency window and permittivity profile of the core due to the strong pump field in the EIT scheme is calculated. For a specific permittivity profile of the core due to EIT, the propagation constant of the weak signal field and spatial shape of fundamental guided mode are calculated by solving the vector wave equation using the finite difference method. It is found that the transparency window and slow light field can be controlled via the optical fibre parameters. The reduced group velocity of slow light in this configuration is useful for many technological applications such as optical memories, effective control of single photon fields, optical buffers and delay lines.

  19. Study of Dynamic Characteristics of Slow-Changing Process

    Directory of Open Access Journals (Sweden)

    Yinong Li

    2000-01-01

    Full Text Available A vibration system with slow-changing parameters is a typical nonlinear system. Such systems often occur in the working and controlled process of some intelligent structures when vibration and deformation exist synchronously. In this paper, a system with slow-changing stiffness, damping and mass is analyzed in an intelligent structure. The relationship between the amplitude and the frequency of the system is studied, and its dynamic characteristic is also discussed. Finally, a piecewise linear method is developed on the basis of the asymptotic method. The simulation and the experiment show that a suitable slow-changing stiffness can restrain the amplitude of the system when the system passes through the resonant region.

  20. Ergodicity and slow diffusion in a supercooled liquid

    Science.gov (United States)

    Bidhoodi, Neeta; Das, Shankar P.

    2016-05-01

    A model for the slow dynamics of the supercooled liquid is formulated in terms of the standard equations of fluctuating nonlinear hydrodynamics (FNH) with the inclusion of an extra diffusive mode for the collective density fluctuations. If the compressible nature of the liquid is completely ignored, this diffusive mode sets the longest relaxation times in the supercooled state and smooths off a possible sharp ergodicity-nonergodicity (ENE) transition predicted in a mode coupling theory. The scenario changes when the complete dynamics is considered with the inclusion of 1 / ρ nonlinearities in the FNH equations, reflecting the compressible nature of the liquid. The latter primarily determines the extent of slowing down in the supercooled liquid. The presence of slow diffusive modes in the supercooled liquid do not give rise to very long relaxation times unless the role of couplings between density and currents in the compressible liquid is negligible.

  1. Shock Formation of Slow Magnetosonic Waves in Coronal Plumes

    Science.gov (United States)

    Cuntz, Manfred; Suess, Steven T.; Rose, M. Franklin (Technical Monitor)

    2001-01-01

    We investigate the height of shock formation in coroner plumes for slow magnetosonic waves. The models take into account plume geometric spreading, heat conduction and radiative damping. The wave parameters as well as the spreading functions of the plumes and the base magnetic field strengths are given by empirical constraints mostly from Solar and Heliospheric Observatory/Ultraviolet Coronagraph Spectrometer (SOHO/UVCS). Our models show that shock formation occurs at low coronal heights, i.e., within 1.3 solar radius, depending on the model parameters. The shock formation is calculated using the well-established wave breaking condition given by the intersection of C+ characteristics in the space-time plane. Our models show that shock heating by slow magnetosonic waves is expected to be relevant at most heights in solar coronal plumes, although slow magnetosonic waves are most likely not a solely operating energy supply mechanism.

  2. Simplified slow anti-coincidence circuit for Compton suppression systems

    International Nuclear Information System (INIS)

    Slow coincidence circuits for the anti-coincidence measurements have been considered for use in Compton suppression technique. The simplified version of the slow circuit has been found to be fast enough, satisfactory and allows an easy system setup, particularly with the advantage of the automatic threshold setting of the low-level discrimination. A well-type NaI detector as the main detector surrounded by plastic guard detector has been arranged to investigate the performance of the Compton suppression spectrometer using the simplified slow circuit. The system has been tested to observe the improvement in the energy spectra for medium to high-energy gamma-ray photons from terrestrial and environmental samples

  3. Simplified slow anti-coincidence circuit for Compton suppression systems.

    Science.gov (United States)

    Al-Azmi, Darwish

    2008-08-01

    Slow coincidence circuits for the anti-coincidence measurements have been considered for use in Compton suppression technique. The simplified version of the slow circuit has been found to be fast enough, satisfactory and allows an easy system setup, particularly with the advantage of the automatic threshold setting of the low-level discrimination. A well-type NaI detector as the main detector surrounded by plastic guard detector has been arranged to investigate the performance of the Compton suppression spectrometer using the simplified slow circuit. The system has been tested to observe the improvement in the energy spectra for medium to high-energy gamma-ray photons from terrestrial and environmental samples. PMID:18222698

  4. The Secreted Protein C1QL1 and Its Receptor BAI3 Control the Synaptic Connectivity of Excitatory Inputs Converging on Cerebellar Purkinje Cells

    Directory of Open Access Journals (Sweden)

    Séverine M. Sigoillot

    2015-02-01

    Full Text Available Precise patterns of connectivity are established by different types of afferents on a given target neuron, leading to well-defined and non-overlapping synaptic territories. What regulates the specific characteristics of each type of synapse, in terms of number, morphology, and subcellular localization, remains to be understood. Here, we show that the signaling pathway formed by the secreted complement C1Q-related protein C1QL1 and its receptor, the adhesion-GPCR brain angiogenesis inhibitor 3 (BAI3, controls the stereotyped pattern of connectivity established by excitatory afferents on cerebellar Purkinje cells. The BAI3 receptor modulates synaptogenesis of both parallel fiber and climbing fiber afferents. The restricted and timely expression of its ligand C1QL1 in inferior olivary neurons ensures the establishment of the proper synaptic territory for climbing fibers. Given the broad expression of C1QL and BAI proteins in the developing mouse brain, our study reveals a general mechanism contributing to the formation of a functional brain.

  5. Evaluation of recombinant outer membrane protein C based indirect enzyme-linked immunoassay for the detection of Salmonella antibodies in poultry

    Directory of Open Access Journals (Sweden)

    Jinu Manoj

    2015-08-01

    Full Text Available Aim: To evaluate the efficacy of recombinant outer membrane proteinC (rOmpC based enzyme-linked immunoassay (ELISA for the diagnosis of salmonellosis in poultry. Materials and Methods: Three antigens were prepared, and the indirect ELISA was standardized using the antigens and the antiserum raised in chicken against Omp and rOmpC. Sera were collected from a total of 255 apparently healthy field chickens and screened for the presence of Salmonella antibodies by this ELISA. Results: The sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of Omp revealed major polypeptides at 36, 42 and 52 kDa, and the rOmpC was evident by a single protein band of 43 kDa. The Omp and rOmpC antigen revealed an optimum concentration of 78 and 156 ng, respectively, in the assay, while the whole cell antigen gave an optimum reaction at a concentration of 106 organisms/ml. The test was found to be specific as it did not react with any of the antisera of seven other organisms. The developed ELISA detected Salmonella antibodies from 22 (8.62% samples with rOmpC antigen, while 24 (9.41% samples gave a positive reaction with both Omp and whole cell antigens. Conclusion: We suggest rOmpC based indirect ELISA as a suitable screening tool for serological monitoring of poultry flocks.

  6. Structure and potential C-terminal dimerization of a recombinant mutant of surfactant-associated protein C in chloroform/methanol.

    Science.gov (United States)

    Luy, Burkhard; Diener, Alexander; Hummel, Rolf-Peter; Sturm, Ernst; Ulrich, Wolf-Rüdiger; Griesinger, Christian

    2004-06-01

    The solution structure of a recombinant mutant [rSP-C (FFI)] of the human surfactant-associated protein C (hSP-C) in a mixture of chloroform and methanol was determined by high-resolution NMR spectroscopy. rSP-C (FFI) contains a helix from Phe5 to the C-terminal Leu34 and is thus longer by two residues than the helix of porcine SP-C (pSP-C), which is reported to start at Val7 in the same solvent. Two sets of resonances at the C-terminus of the peptide were observed, which are explained by low-order oligomerization, probably dimerization of rSP-C (FFI) in its alpha-helical form. The dimerization may be induced by hydrogen bonding of the C-terminal carboxylic groups or by the strictly conserved C-terminal heptapeptide segment with a motif similar to the GxxxG dimerization motif of glycophorin A. Dimerization at the heptapeptide segment would be consistent with findings based on electrospray ionization MS data, chemical cross-linking studies, and CNBr cleavage data. PMID:15153097

  7. Treatment of chronic diabetic lower leg ulcers with activated protein C: a randomised placebo-controlled, double-blind pilot clinical trial.

    Science.gov (United States)

    Whitmont, Kaley; McKelvey, Kelly J; Fulcher, Gregory; Reid, Ian; March, Lyn; Xue, Meilang; Cooper, Alan; Jackson, Christopher J

    2015-08-01

    Lower leg ulcers are a serious and long-term complication in patients with diabetes and pose a major health concern because of the increasing number of patients diagnosed with diabetes each year. This study sought to evaluate the clinical benefit of topical activated protein C (APC) on chronic lower leg ulcers in patients with diabetes. Twelve patients were randomly assigned to receive either APC (N = 6) or physiological saline (placebo; N = 6) in a randomised, placebo-controlled, double-blind pilot clinical trial. Treatment was administered topically, twice weekly for 6 weeks with final follow-up at 20 weeks. Wound area was significantly reduced to 34·8 ± 16·4% of week 0 levels at 20 weeks in APC-treated wounds (p = 0·01). At 20 weeks, three APC-treated wounds had completely healed, compared to one saline-treated wound. Full-thickness wound edge skin biopsies showed reduced inflammatory cell infiltration and increased vascular proliferation following APC treatment. Patient stress scores were also significantly reduced following APC treatment (p ulcers in patients with diabetes and provides supporting evidence for a larger clinical trial. PMID:23848141

  8. Slow Drift-Oscillations of a Ship in Irregular Waves

    Directory of Open Access Journals (Sweden)

    Odd M. Faltinsen

    1980-10-01

    Full Text Available A procedure to calculate horizontal slow drift excitation forces on an infinitely long horizontal cylinder in irregular beam sea waves is presented. The hydrodynamic boundary-value problem is solved correctly to second order in wave amplitude. Results in the form of second order transfer functions are presented for different, two-dimensional shapes. It is concluded that Newman's approximative method is a practical way to calculate slow drift excitation forces on a ship in beam sea and it is suggested that it may be used in a more general case. Applications of the results for moored ships are discussed.

  9. Computation of saddle-type slow manifolds using iterative methods

    DEFF Research Database (Denmark)

    Kristiansen, Kristian Uldall

    2015-01-01

    This paper presents an alternative approach for the computation of trajectory segments on slow manifolds of saddle type. This approach is based on iterative methods rather than collocation-type methods. Compared to collocation methods, which require mesh refinements to ensure uniform convergence...... with respect to , appropriate estimates are directly attainable using the method of this paper. The method is applied to several examples, including a model for a pair of neurons coupled by reciprocal inhibition with two slow and two fast variables, and the computation of homoclinic connections in the...

  10. Interventions to Slow Aging in Humans: Are We Ready?

    OpenAIRE

    Longo, Valter D.; Antebi, Adam; Bartke, Andrzej; Barzilai, Nir; Brown-Borg, Holly M.; Caruso, Calogero; Curiel, Tyler J.; de Cabo, Rafael; Franceschi, Claudio; Gems, David; Ingram, Donald K.; Johnson, Thomas E.; Kennedy, Brian K.; Kenyon, Cynthia; Klein, Samuel

    2015-01-01

    The workshop entitled ‘Interventions to Slow Aging in Humans: Are We Ready?’ was held in Erice, Italy, on October 8–13, 2013, to bring together leading experts in the biology and genetics of aging and obtain a consensus related to the discovery and development of safe interventions to slow aging and increase healthy lifespan in humans. There was consensus that there is sufficient evidence that aging interventions will delay and prevent disease onset for many chronic conditions of adult and ol...

  11. Is There Slow Slip on the Wasatch Fault?

    OpenAIRE

    Jeppson, Tamara N.

    2009-01-01

    To accurately determine the earthquake hazard posed by a fault, we need to understand both strain accumulation and release along the fault. Strain accumulates during aseismic periods but it is released during fault slip events that can be either seismic or aseismic. Aseismic slow slip events are motions similar to earthquakes but they occur over much longer timescales. Slow slip is not felt at the Earth’s surface but it can be recorded in GPS time series. A deformation modeling tool that was ...

  12. Passive integrated circuits utilizing slow light in photonic crystal waveguides

    DEFF Research Database (Denmark)

    Lavrinenko, Andrei; Têtu, Amélie; Yang, Lirong;

    2006-01-01

    We report thorough investigations of photonic crystal waveguide properties in the slow light regime. The transmission and the group index near the cutoff wavelengths oscillate in phase in close analogy with the ID photonic crystal behavior. The influence of having a finite number of periods in the...... photonic crystal waveguide is addressed to explain the spiky character of both the transmission and group index spectra. The profile of the slow-light modes is stretched out into the first and second rows of the holes closest to the waveguide channel. One of our strategies to ameliorate the design of...

  13. Spontaneous neural activity during human slow wave sleep

    OpenAIRE

    Dang-Vu, Thien Thanh; Schabus, Manuel; Desseilles, Martin; Albouy, Geneviève; Boly, Mélanie; Darsaud, Annabelle; Gais, Steffen; Rauchs, Géraldine; Sterpenich, Virginie; Vandewalle, Gilles; Carrier, Julie; Moonen, Gustave; Balteau, Evelyne; Degueldre, Christian; Luxen, André

    2008-01-01

    Slow wave sleep (SWS) is associated with spontaneous brain oscillations that are thought to participate in sleep homeostasis and to support the processing of information related to the experiences of the previous awake period. At the cellular level, during SWS, a slow oscillation (140 μV) and delta waves (75–140 μV) during SWS in 14 non-sleep-deprived normal human volunteers. Significant increases in activity were associated with these waves in several cortical areas, including the inferior f...

  14. Wide-band slow-wave systems simulation and applications

    CERN Document Server

    Staras, Stanislovas

    2012-01-01

    The field of electromagnetics has seen considerable advances in recent years, based on the wide applications of numerical methods for investigating electromagnetic fields, microwaves, and other devices. Wide-Band Slow-Wave Systems: Simulation and Applications presents new technical solutions and research results for the analysis, synthesis, and design of slow-wave structures for modern electronic devices with super-wide pass-bands. It makes available, for the first time in English, significant research from the past 20 years that was previously published only in Russian and Lithuanian. The aut

  15. The energy storage in the formation of slow light

    Science.gov (United States)

    Shakhmuratov, R. N.

    2010-08-01

    Slow light formation in media with (i) an electromagnetically induced transparency, (ii) a doublet structure, and (iii) a single absorption line, detuned from resonance, is considered with the help of a simple model. The model is based on the description of particles in these media by a pseudospin 1/2, which is subject to two 'orthogonal fields'. We mainly focus on the analysis of the reversible process of the particle excitation-de-excitation resulting in the temporal storage of the light-pulse energy without the pulse corruption. The influence of irreversible relaxation processes on the slow light formation is studied.

  16. Enhancement of rabbit protein S anticoagulant cofactor activity in vivo by modulation of the protein S C4B binding protein interaction.

    OpenAIRE

    Weinstein, R E; Walker, F. J.

    1990-01-01

    The carboxy-terminal region of protein S has been recently been observed to be involved in the interaction between protein S and C4b-binding protein (Walker, F. J. 1989. J. Biol. Chem. 264:17645-17658). A synthetic peptide, GVQLDLDEAI, corresponding to that region of protein S has been used to investigate the protein S/C4b-binding protein interaction in vitro and in vivo. Rabbit activated protein C possesses species-specific anticoagulant activity for which rabbit protein S functions as a cof...

  17. High affinity binding of [3H]cocaine to rat liver microsomes

    International Nuclear Information System (INIS)

    ]3H]cocaine bound reversible, with high affinity and stereospecificity to rat liver microsomes. Little binding was detected in the lysosomal, mitochondrial and nuclear fractions. The binding kinetics were slow and the kinetically calculated K/sub D/ was 2 nM. Induction of mixed function oxidases by phenobarbital did not produce significant change in [3H]cocaine binding. On the other hand, chronic administration of cocaine reduced [3H]cocaine binding drastically. Neither treatment affected the affinity of the liver binding protein for cocaine. Microsomes from mouse and human livers had less cocaine-binding protein and lower affinity for cocaine than those from rat liver. Binding of [3H]cocaine to rat liver microsomes was insensitive to monovalent cations and > 10 fold less sensitive to biogenic amines than the cocaine receptor in rat striatum. However, the liver protein had higher affinity for cocaine and metabolites except for norcocaine. Amine uptake inhibitors displaced [3H]cocaine binding to liver with a different rank order of potency than their displacement of [3H]cocaine binding to striatum. This high affinity [3H]cocaine binding protein in liver is not likely to be monooxygenase, but may have a role in cocaine-induced hepatotoxicity

  18. A prospective cohort study on the absolute risks of venous thromboembolism and predictive value of screening asymptomatic relatives of patients with hereditary deficiencies of protein S, protein C or antithrombin.

    NARCIS (Netherlands)

    Mahmoodi, B.K.; Brouwer, J.L.P.; Kate, M.K. Ten; Lijfering, W.M.; Veeger, N.J.; Mulder, A.B.; Kluin-Nelemans, H.C.; Meer, J. van der

    2010-01-01

    BACKGROUND: Absolute risks of venous thromboembolism (VTE) in protein S-, protein C-, or antithrombin-deficient subjects are mainly based on retrospective data. Screening asymptomatic relatives of these patients is disputed, though studies addressing this issue have yet to be conducted. METHODS: We

  19. Slowing down of fast atoms in a uniform gas

    International Nuclear Information System (INIS)

    The nonlinear Boltzmann equation is modified to describe the slowing down of fast particles, i.e., those with energies very much greater than thermal values. Two situations are discussed: (1) the foreign gas, in which fast alien particles are followed after their injection into the host; and (2) the single gas, in which a fast disturbance in the host is examined as the particles in it share their energies by generating recoils. Using a scattering cross section derived from a modified inverse power law of interaction, we obtain exact solutions by Mellin transforms of the time-energy evolution of the particles. The mean energy dissipation rate, the average number of recoils generated, and the slowing-down times are studied for a variety of scattering models. It is concluded that, in general, the slowing-down time of particles in the single gas is longer than those of the foreign gas, when scaled in units of the mean free time at source energy. We also find that, for a given total cross section energy variation, as the scattering becomes more anisotropic in the center-of-mass system, the particles of the foreign gas take longer to slow down, whereas those in the single gas take a shorter time. An explanation of this anomalous behavior is advanced

  20. Nonhuman Primates Prefer Slow Tempos but Dislike Music Overall

    Science.gov (United States)

    McDermott, Josh; Hauser, Marc D.

    2007-01-01

    Human adults generally find fast tempos more arousing than slow tempos, with tempo frequently manipulated in music to alter tension and emotion. We used a previously published method [McDermott, J., & Hauser, M. (2004). Are consonant intervals music to their ears? Spontaneous acoustic preferences in a nonhuman primate. Cognition, 94(2), B11-B21]…

  1. Slow light based on material and waveguide dispersion

    DEFF Research Database (Denmark)

    Nielsen, Torben Roland; Lavrinenko, Andrei; Mørk, Jesper

    2009-01-01

    We study slow light pulse propagation in a photonic crystal structure consisting of a dispersive and absorptive dielectric material and compare it with the constant wave case. The group index and the trasmission are investigated for the example of an ensemble of semiconductor quantum dots embedded...

  2. The fundamental Diagram of Pedestrian Model with Slow Reaction

    CERN Document Server

    Fang, Jun; Hu, Hao; Xu, Zhaohui; Li, Huan

    2015-01-01

    The slow-to-start models are a classical cellular automata model in simulating vehicle traffic. However, to our knowledge, the slow-to-start effect has not considered in modeling pedestrian dynamic. We verify the similar behavior between pedestrian and vehicle, and propose an new lattice gas (LG) model called the slow reaction (SR) model to describe the pedestrian's delayed reaction in single-file movement. We simulate and reproduce the Seyfried's field experiments at the research centre Julich, and use its empirical data to validate our SR model. We compare the SR model with the standard LG model. We test different probability of slow reaction ps in SR model and found the simulation data of ps=0.3 fit the empirical data best. The RMS error of mean velocity of SR model is smaller than that of standard LG model. In the range of ps=0.1~0.3, our fundamental diagram between velocity and density by simulation coincides with field experiments. The distribution of individual velocity in fundamental diagram in SR mod...

  3. Optical signal processing using slow and fast light technologies

    DEFF Research Database (Denmark)

    Capmany, J.; Sales, Salvador; Xue, Weiqi;

    2009-01-01

    We review the theory of slow and fat light effects due to coherent population oscillations in semiconductor waveguides, which can be potentially applied in microwave photonic systems as a RF phase shifters. In order to satisfy the application requirement of 360 degrees RF phase shift at different...

  4. Quadrature of one integral solution of transport slowing down equation

    International Nuclear Information System (INIS)

    Analytical solution of neutron slowing down equation leads to numerical calculation of neutron flux for estimated energy values. This paper shows that Newton interpolation for obtaining tabulated values of effective cross sections and application of Gauss quadrature formula for numerical integration are valid

  5. One Size Fits All? Slow Cortical Potentials Neurofeedback: A Review

    Science.gov (United States)

    Mayer, Kerstin; Wyckoff, Sarah N.; Strehl, Ute

    2013-01-01

    Objective: The intent of this manuscript was to review all published studies on slow cortical potentials (SCP) neurofeedback for the treatment of ADHD, with emphasis on neurophysiological rationale, study design, protocol, outcomes, and limitations. Method: For review, PubMed, MEDLINE, ERIC, and Google Scholar searches identified six studies and…

  6. Thermodynamics of Gases: Combustion Processes, Analysed in Slow Motion

    Science.gov (United States)

    Vollmer, Michael; Mollmann, Klaus-Peter

    2013-01-01

    We present a number of simple demonstration experiments recorded with high-speed cameras in the fields of gas dynamics and thermal physics. The experiments feature relatively slow combustion processes of pure hydrogen as well as fast reactions involving oxy-hydrogen in a stoichiometric mixture. (Contains 4 figures.)

  7. Reduction in slow intercompartmental clearance of urea during dialysis

    International Nuclear Information System (INIS)

    The kinetics of urea and inulin were analyzed in five anesthetized dogs during sequential 2-hour periods before, during, and after hemodialysis. The distribution of both compounds after simultaneous intravenous injection was characterized by three-compartment models, and the total volumes of urea (0.66 +/- 0.05 L/kg) and inulin (0.19 +/- 0.01 L/kg) distribution were similar to expected values for total body water and extravascular space, respectively. Intercompartmental clearances calculated before dialysis were used to estimate blood flows to the fast and slow equilibrating compartments. In agreement with previous results, the sum of these flows was similar to cardiac output, averaging 101% of cardiac output measured before dialysis (range 72% to 135%). Dialysis was accompanied by reductions in the slow intercompartmental clearances of urea (81%) and inulin (47%), which reflected a 90% attenuation in blood flow supplying the slow equilibrating compartments. This was estimated to result in a 10% average reduction in the efficiency with which urea was removed by dialysis (range 2.0% to 16.4%). Mean arterial pressure fell by less than 5% during dialysis, but total peripheral resistance increased by 47% and cardiac output fell by 35%. In the postdialysis period, total peripheral resistance and cardiac output returned toward predialysis values, but blood flow to the slow equilibrating peripheral compartment was still reduced by 80%. These changes parallel activation of the renin-angiotensin system, but further studies are required to establish causality

  8. Current drive by synergy of slow modes in tokamaks

    International Nuclear Information System (INIS)

    Enhancement of lower hybrid current drive in the presence of wave converted ion-ion slow modes is discussed using a one-dimensional quasi-linear equation. The special case in which the slow mode resulting from conversion in a deuterium-hydrogen mixture is absorbed by low energy electrons is considered in detail. In this scheme, the effect of the ion-ion modes is to increase the electron tail density, and the current enhancement is given by the ratio of the parallel velocity distributions with and without mode converted slow modes, calculated at the lower pparallel limit of the lower hybrid (LH) tail. The method of synergy is suited for remote control of the LH fast tail population, and is useful for current drive optimization. The computation also gives some insight into current drive by ion-ion slow modes in the absence of LH waves, a situation of relevance in a high temperature plasma where LH accessibility is severely reduced. (author). 8 refs, 5 figs

  9. A New Approach to Charged Particle Slowing Down and Dispersion

    Energy Technology Data Exchange (ETDEWEB)

    Stevens, David E. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2016-03-24

    The process by which super-thermal ions slow down against background Coulomb potentials arises in many fields of study. In particular, this is one of the main mechanisms by which the mass and energy from the reaction products of fusion reactions is deposited back into the background. Many of these fields are characterized by length and time scales that are the same magnitude as the range and duration of the trajectory of these particles, before they thermalize into the background. This requires numerical simulation of this slowing down process through numerically integrating the velocities and energies of these particles. This paper first presents a simple introduction to the required plasma physics, followed by the description of the numerical integration used to integrate a beam of particles. This algorithm is unique in that it combines in an integrated manner both a second-order integration of the slowing down with the particle beam dispersion. These two processes are typically computed in isolation from each other. A simple test problem of a beam of alpha particles slowing down against an inert background of deuterium and tritium with varying properties of both the beam and the background illustrate the utility of the algorithm. This is followed by conclusions and appendices. The appendices define the notation, units, and several useful identities.

  10. Slow light enhancement and limitations in periodic media

    DEFF Research Database (Denmark)

    Grgic, Jure

    slowly propagating light. By means of perturbative analysis, we address the effect of small imperfections in periodic structures. From our analysis, we find very universal behavior in a slow light regime for all periodic structures. Even if losses are very small the dispersion is severely affected in the...

  11. Some techniques to improve time structure of slow extracted beam

    International Nuclear Information System (INIS)

    In order to improve the time structure of slow extracted beam spill for the KEK 12GeV PS, the spill control system has been upgraded by adding feed forward signal to feedback signal. Further, the wake field in the RF cavity has been cancelled by the beam bunch signal to reduce the re-bunch effect during extraction period. (author)

  12. Decision processes and the slowing of simple choices in schizophrenia.

    Science.gov (United States)

    Heathcote, Andrew; Suraev, Anna; Curley, Samuel; Gong, Qinchun; Love, Jonathon; Michie, Patricia T

    2015-11-01

    Individuals diagnosed with schizophrenia have slowed response times (RT). We examined the role of decision processes in the slowing of simple choice responses. We updated Schatz's (1998) meta-analysis of deficits in speed and extend it to systematically examine the effects of schizophrenia on choice accuracy. We then report an experiment requiring decisions about motion direction, which we analyzed using an evidence accumulation model of choice, the linear ballistic accumulator (LBA; Brown & Heathcote, 2008). By simultaneously taking into account all aspects of behavior, the LBA was more sensitive to deficits than mean RT or accuracy alone. It also identified the 2 underlying causes of slowing: more cautious decisions (i.e., requiring more evidence before making a decision) and perceptual deficits. The schizophrenia group displayed strong sequential effects that were captured by the response on the previous trial affecting the relative amount of evidence required for choice in the LBA. These results illustrate that evidence accumulation models provide a sensitive tool that can be used to identify the cognitive mechanisms causing slowing in schizophrenia. PMID:26595475

  13. Quadrature of an integral solution of slowing down transport equation

    International Nuclear Information System (INIS)

    Full text: Numerical solution of the slowing-down equation is derived from analytical solution for neutron flux for given values of energy. It is shown in this paper that the application of Newton interpolation for obtaining effective cross sections as well as Gauss quadrature formula for numerical integration is justified

  14. Slow: A Tool for Reporting and Diagnosing Performance Problems

    Science.gov (United States)

    Root, Darrell; Liviero, Belinda; Lasinski, Tom (Technical Monitor)

    1998-01-01

    Slow is a bourne shell script which is meant to be run by workstation users who are suffering performance problems. It collects a snapshot of performance data using previously published and publicly available diagnostic commands. This paper discusses how to interpret the output of those commands to identify the root-cause of unix workstation performance problems.

  15. Slow-light enhancement of Beer-Lambert-Bouguer absorption

    CERN Document Server

    Mortensen, N A; Mortensen, Niels Asger; Xiao, Sanshui

    2007-01-01

    We theoretically show how slow light in an optofluidic environment facilitates enhanced light-matter interactions, by orders of magnitude. The proposed concept provides strong opportunities for improving existing miniaturized chemical absorbance cells for Beer-Lambert-Bouguer absorption measurements widely employed in analytical chemistry.

  16. Slow Manifold and Hannay Angle in the Spinning Top

    Science.gov (United States)

    Berry, M. V.; Shukla, P.

    2011-01-01

    The spin of a top can be regarded as a fast variable, coupled to the motion of the axis which is slow. In pure precession, the rotation of the axis round a cone (without nutation), can be considered as the result of a reaction from the fast spin. The resulting restriction of the total state space of the top is an illustrative example, at…

  17. Biochar production from freshwater algae by slow pyrolysis

    Directory of Open Access Journals (Sweden)

    Tanongkiat Kiatsiriroat

    2012-05-01

    Full Text Available A study on the feasibility of biochar production from 3 kinds of freshwateralgae, viz. Spirulina, Spirogyra and Cladophora, was undertaken. Using a slow pyrolysis process in a specially designed reactor, biochar could be generated at 550oC under nitrogen atmosphere. The yields of biochar were between 28-31% of the dry algae.

  18. Biochar production from freshwater algae by slow pyrolysis

    OpenAIRE

    Tanongkiat Kiatsiriroat

    2012-01-01

    A study on the feasibility of biochar production from 3 kinds of freshwateralgae, viz. Spirulina, Spirogyra and Cladophora, was undertaken. Using a slow pyrolysis process in a specially designed reactor, biochar could be generated at 550oC under nitrogen atmosphere. The yields of biochar were between 28-31% of the dry algae.

  19. The very slow solar wind: Properties, origin and variability

    Science.gov (United States)

    Sanchez-Diaz, Eduardo; Rouillard, Alexis P.; Lavraud, Benoit; Segura, Kevin; Tao, Chihiro; Pinto, Rui; Sheeley, N. R.; Plotnikov, Illya

    2016-04-01

    Solar wind slower than 300 km/s, hereafter termed very slow solar wind (VSSW), is seldom observed at 1 AU. It was, however, commonly measured inside 0.7 AU by the two Helios spacecraft, particularly during solar maximum. Magnetohydrodynamic (MHD) modeling reveals that the disappearance of VSSW at 1 AU is the result of its interaction with faster solar wind. The acceleration and compression of the VSSW contributes to the observed highly variable structure of the slow solar wind at 1 AU. The VSSW usually contains the heliospheric plasma sheet and current sheet. It has higher density and lower temperature than the regular slow solar wind, extending the known scaling laws below 300 km/s. Its helium abundance increases with solar activity even more significantly than the slow solar wind. Contrary to faster solar winds, the helium ions in the VSSW are slower than the dominant protons. Combining a Potential Field Source Surface (PFSS) model with ballistic back tracing, we study the source region of the VSSW. We show that the proton density flux for the VSSW is much higher than for the faster winds, particularly at solar maximum.

  20. Cellulose-Lignin interactions during slow and fast pyrolysis

    NARCIS (Netherlands)

    Hilbers, T.J.; Wang, Z.; Pecha, B.; Westerhof, R.J.M.; Kersten, S.R.A.; Pelaez-Samaniego, M.R.; Garcia-Perez, M.

    2015-01-01

    The interactions between lignin and cellulose during the slow pyrolysis of their blends were studied by means of Thermogravimetric Analysis (TGA) and Scanning Electron Microscopy (SEM). Fast pyrolysis was studied using Pyrolysis-Gas Chromatography/Mass Spectroscopy (Py–GC/MS). Crystalline cellulose

  1. Enhanced circular dichroism via slow light in dispersive structured media

    DEFF Research Database (Denmark)

    Pedersen, Jesper Goor; Mortensen, Asger

    2007-01-01

    Circular dichroism (CD) is in widespread use as a means of determining enantiomeric excess. We show how slow-light phenomena in dispersive structured media allow for a reduction in the required optical path length of an order of magnitude. The same ideas may be used to enhance the sensitivity of CD...

  2. Precision compliance techniques for slow crack growth measurements

    Science.gov (United States)

    Noronha, P. J.

    1975-01-01

    A method is presented for using simple electronic components to obtain the high sensitivity needed to measure very slow crack growth rates. The technique presented can reduce the experimental time considerably and also yield a greater amount of data more accurately than optical techniques for measuring crack growth rates.

  3. Coaxial slow source: a quasi-static FRC formation concept

    International Nuclear Information System (INIS)

    The electromagnetics of one of several techniques for generating FRCs in a coaxial configuration has been presented. It has been shown that the discussed design satisfies all the electromagnetic requirements for a slow source. The next major issue is the investigation of the plasma physics which will ultimately determine the viability of this concept

  4. Coaxial slow source: a quasi-static FRC formation concept

    Energy Technology Data Exchange (ETDEWEB)

    McKenna, K.F.; Gribble, R.F.

    1984-01-01

    The electromagnetics of one of several techniques for generating FRCs in a coaxial configuration has been presented. It has been shown that the discussed design satisfies all the electromagnetic requirements for a slow source. The next major issue is the investigation of the plasma physics which will ultimately determine the viability of this concept.

  5. Slow solar wind boundaries and implication for its formation

    Science.gov (United States)

    Ko, Yuan-Kuen; Roberts, Aaron; Lepri, Susan; Kocher, Manan

    2015-04-01

    Solar wind and the associated magnetic field permeate the heliosphere. Their temporal and spatial variations contribute significantly in the large range of variations in related geomagnetic effects as well as in the properties of solar energetic particles. Among the least understood is the slow solar wind for how it is formed at the Sun and what causes the large variations in its physical properties. This work investigates the variations in the slow solar wind streams measured in-situ at 1 AU and the correlations among the protons, heavy ions, suprathermal electrons, and magnetic field properties. Besides well-established correlations among the proton speed, proton temperature and ion charge states, we also found certain distinct characteristics in the correlation and temporal relationship between the ion charge states, proton velocity fluctuations and, in many cases, suprathermal electron halos. The implications from our findings in the slow wind formation and whether the slow wind has a distinct boundary with the fast wind will be discussed.

  6. An Energy Filter for Slow Positron Beam Using Cosine Coils

    Institute of Scientific and Technical Information of China (English)

    R.S.Yu; B.Y.Wang; 等

    2001-01-01

    A novel charged-particle velocity filter for slow positron beam has been successfully built and tested.It is a pure magnetic system composed of three magnetic fields,two of them are pure dipole magnetic fields generated by two symmetrically put cosine coils.The physical principle and the performance of the cosine coils are reviewed.

  7. Topographic abnormality of slow cortical potentials in schizophrenia

    Directory of Open Access Journals (Sweden)

    L.F.H. Basile

    2004-01-01

    Full Text Available A recent study from our laboratory has provided evidence for the generation of slow potentials occurring in anticipation to task-performance feedback stimuli, in multiple association cortical areas, consistently including two prefrontal areas. In the present study, we intended to determine whether these slow potentials would indicate some abnormality (topographic in schizophrenic patients, and thus serve as an indication of abnormal association cortex activity. We recorded slow potentials while subjects performed a paired-associates memory task. A 123-channel EEG montage and common average reference were used for 20 unmedicated schizophrenic (mean duration of illness: 11.3 ± 9.2 years; mean number of previous hospitalizations: 1.2 ± 1.9 and 22 healthy control subjects during a visual paired-associates matching task. For the topographic analysis, we used a simple index of individual topographic deviation from normality, corrected for absolute potential intensities. Slow potentials were observed in all subjects. Control subjects showed a simple spatial pattern of voltage extrema (left central positive and right prefrontal negative, whereas schizophrenic patients presented a more complex, fragmented pattern. Topographic deviation was significantly different between groups (P < 0.001. The increased topographic complexity in schizophrenics could be visualized in grand averages computed across subjects. Increased topographic complexity could also be seen when grand averages were computed for subgroups of patients assembled either according to task-performance (high versus low or by their scores on psychopathological scales. There was no significant correlation between topographic deviation and psychopathology scores. We conclude that the slow potential topographic abnormalities of schizophrenia indicate an abnormality in the configuration of large-scale electrical activity in association cortices.

  8. A MODEL FOR THE SOURCES OF THE SLOW SOLAR WIND

    International Nuclear Information System (INIS)

    Models for the origin of the slow solar wind must account for two seemingly contradictory observations: the slow wind has the composition of the closed-field corona, implying that it originates from the continuous opening and closing of flux at the boundary between open and closed field. On the other hand, the slow wind also has large angular width, up to ∼600, suggesting that its source extends far from the open-closed boundary. We propose a model that can explain both observations. The key idea is that the source of the slow wind at the Sun is a network of narrow (possibly singular) open-field corridors that map to a web of separatrices and quasi-separatrix layers in the heliosphere. We compute analytically the topology of an open-field corridor and show that it produces a quasi-separatrix layer in the heliosphere that extends to angles far from the heliospheric current sheet. We then use an MHD code and MDI/SOHO observations of the photospheric magnetic field to calculate numerically, with high spatial resolution, the quasi-steady solar wind, and magnetic field for a time period preceding the 2008 August 1 total solar eclipse. Our numerical results imply that, at least for this time period, a web of separatrices (which we term an S-web) forms with sufficient density and extent in the heliosphere to account for the observed properties of the slow wind. We discuss the implications of our S-web model for the structure and dynamics of the corona and heliosphere and propose further tests of the model.

  9. GLUT4 is reduced in slow muscle fibers of type 2 diabetic patients: is insulin resistance in type 2 diabetes a slow, type 1 fiber disease?

    DEFF Research Database (Denmark)

    Gaster, M; Staehr, P; Beck-Nielsen, H;

    2001-01-01

    morphometry, GLUT4 density was found to be significantly higher in slow compared with fast fibers in biopsy specimens from lean and obese subjects. In contrast, in type 2 diabetic subjects, GLUT4 density was significantly lower in slow compared with fast fibers. GLUT4 density in slow fibers from diabetic...

  10. Comparative response of platelet fV and plasma fV to activated protein C and relevance to a model of acute traumatic coagulopathy.

    Directory of Open Access Journals (Sweden)

    James E Campbell

    Full Text Available BACKGROUND: Acute traumatic coagulopathy (ATC has been linked to an increase in activated protein C (aPC from 40 pM in healthy individuals to 175 pM. aPC exerts its activity primarily through cleavage of active coagulation factor Va (fVa. Platelets reportedly possess fVa which is more resistant to aPC cleavage than plasma fVa; this work examines the hypothesis that normal platelets are sufficient to maintain coagulation in the presence of elevated aPC. METHODS: Coagulation responses of normal plasma, fV deficient plasma (fVdp, and isolated normal platelets in fVdp were conducted: prothrombin (PT tests, turbidimetry, and thromboelastography (TEG, including the dose response of aPC on the samples. RESULTS: PT and turbidimetric assays demonstrate that normal plasma is resistant to aPC at doses much higher than those found in ATC. Additionally, an average physiological number of washed normal platelets (200,000 platelets/mm3 was sufficient to eliminate the anti-coagulant effects of aPC up to 10 nM, nearly two orders of magnitude above the ATC concentration and even the steady-state pharmacological concentration of human recombinant aPC, as measured by TEG. aPC also demonstrated no significant effect on clot lysis in normal plasma samples with or without platelets. CONCLUSIONS: Although platelet fVa shows slightly superior resistance to aPC's effects compared to plasma fVa in static models, neither fVa is sufficiently cleaved in simulations of ATC or pharmacologically-delivered aPC to diminish coagulation parameters. aPC is likely a correlative indicator of ATC or may play a cooperative role with other activity altering products generated in ATC.

  11. Soluble endothelial protein C receptor (sEPCR) is likely a biomarker of cancer-associated hypercoagulability in human hematologic malignancies

    International Nuclear Information System (INIS)

    Elevated plasma level of soluble endothelial protein C receptor (sEPCR) may be an indicator of thrombotic risk. The present study aims to correlate leukemia-associated hypercoagulability to high level plasma sEPCR and proposes its measurement in routine clinical practice. EPCR expressions in leukemic cell lines were determined by flow cytometry, immunocytochemistry, and reverse transcription polymerase chain reaction (RT-PCR). EPCR gene sequence of a candidate cell line HL-60 was also determined. Plasma samples (n = 76) and bone marrow aspirates (n = 72) from 148 patients with hematologic malignancies and 101 healthy volunteers were analyzed by enzyme-linked immunosorbent assay (ELISA) via a retrospective study for sEPCR and D-dimer. All leukemic cell lines were found to express EPCR. Also, HL-60 EPCR gene sequence showed extensive similarities with the endothelial reference gene. All single nucleotide polymorphisms (SNPs) originally described and some new SNPs were revealed in the promoter and intronic regions. Among these patients 67% had plasma sEPCR level higher than the controls (100 ± 28 ng/mL), wherein 16.3% patients had experienced a previous thrombotic event. These patients were divided into: group-1 (n = 45) with amount of plasmatic sEPCR below 100 ng/mL, group-2 (n = 45) where the concentration of sEPCR was between 100 and 200, and group-3 (n = 20) higher than 200 ng/mL. The numbers of thrombotic incidence recorded in each group were four, six, and eight, respectively. These results reveal that EPCR is expressed not only by a wide range of human malignant hematological cells but also the detection of plasma sEPCR levels provides a powerful insight into thrombotic risk assessment in cancer patients, especially when it surpasses 200 ng/mL

  12. Impact of hormone-associated resistance to activated protein C on the thrombotic potential of oral contraceptives: a prospective observational study.

    Directory of Open Access Journals (Sweden)

    Heiko Rühl

    Full Text Available The increased thrombotic risk of oral contraceptives (OC has been attributed to various alterations of the hemostatic system, including acquired resistance to activated protein C (APC. To evaluate to what extent OC-associated APC resistance induces a prothrombotic state we monitored plasma levels of thrombin and molecular markers specific for thrombin formation in women starting OC use. Elevated plasma levels of thrombin have been reported to characterize situations of high thrombotic risk such as trauma-induced hypercoagulability, but have not yet been studied during OC use.Blood samples were collected prospectively from healthy women (n = 21 before and during three menstruation cycles after start of OC. APC resistance was evaluated using a thrombin generation-based assay. Plasma levels of thrombin and APC were directly measured using highly sensitive oligonucleotide-based enzyme capture assay (OECA technology. Thrombin generation markers and other hemostasis parameters were measured additionally.All women developed APC resistance as indicated by an increased APC sensitivity ratio compared with baseline after start of OC (p = 0.0003. Simultaneously, plasma levels of thrombin, prothrombin fragment 1+2, and of thrombin-antithrombin complexes did not change, ruling out increased thrombin formation. APC plasma levels were also not influenced by OC use, giving further evidence that increased thrombin formation did not occur.In the majority of OC users no enhanced thrombin formation occurs despite the development of APC resistance. It cannot be ruled out, however, that thrombin formation might occur to a greater extent in the presence of additional risk factors. If this were the case, endogenous thrombin levels might be a potential biomarker candidate to identify women at high thrombotic risk during OC treatment. Large-scale studies are required to assess the value of plasma levels of thrombin as predictors of OC-associated thrombotic risk.

  13. Cleavage at both Arg306 and Arg506 is required and sufficient for timely and efficient inactivation of factor Va by activated protein C*

    Science.gov (United States)

    Barhoover, Melissa A.; Kalafatis, Michael

    2011-01-01

    Background Activated protein C (APC) inactivates membrane-bound factor Va following cleavages of the heavy chain at Arg306, Arg506, and Arg679. Objectives To examine which cleavage is most important for inactivation, recombinant factor V molecules were constructed as follows: factor V306Q (R306→Q), factor V506Q (R506→Q), and factor V306Q/506Q (R306→Q and R506→Q). Methods The recombinant molecules were expressed in mammalian cells, purified, and assayed prior and after incubation with APC and lipids for 30 min (factor Vai) in clotting assays and in an assay using purified reagents and saturating concentrations of factor Va. Results Clotting assays demonstrated that factor VaiWT, factor Vai306Q and factor Vai506Q were devoid of activity, while factor Vai306Q/506Q maintained ~70% activity following a 30 minute incubation with APC. Prothrombinase assembled with all mutant cofactor molecules before and after treatment with APC had Km values similar to values found with prothrombinase assembled with factor VaWT. Prothrombinase assembled with factor VaiWT demonstrated 20-fold reduction in kcat, while prothrombinase assembled with factor Vai506Q had a 2-fold reduction in kcat as compared to prothrombinase assembled with factor VaWT. In contrast, factor Vai306Q and factor Vai306Q/506Q didn’t show any loss in kcat under similar experimental conditions. Conclusion Our data demonstrate that: 1) the activity of an APC-treated factor Va molecule bearing a single mutation at Arg306 or Arg506 depends on the assay used; and 2) regardless of the assay employed, in the absence of the APC-cleavage sites at Arg306 and Arg506, the active cofactor is unable to be significantly inactivated by APC in the presence of a membrane surface. PMID:21467919

  14. Children with Dyslexia Are Slow Writers Because They Pause More Often and Not Because They Are Slow at Handwriting Execution

    Science.gov (United States)

    Sumner, Emma; Connelly, Vincent; Barnett, Anna L.

    2013-01-01

    It is commonly assumed that children with dyslexia are slower at handwriting than other children. However, evidence of slow handwriting in children with dyslexia is very mixed. Thirty-one children with dyslexia, aged 9 years, were compared to both age-matched children and younger spelling-ability matched children. Participants completed an…

  15. Functional Analysis of Slow Myosin Heavy Chain 1 and Myomesin-3 in Sarcomere Organization in Zebrafish Embryonic Slow Muscles

    Institute of Scientific and Technical Information of China (English)

    Jin Xu; Jie Gao; Junling Li; Liangyi Xue; Karl J. Clark; Stephen C. Ekker; Shao Jun Du

    2012-01-01

    Myofibrillogenesis,the process of sarcomere formation,requires close interactions of sarcomeric proteins and various components of sarcomere structures.The myosin thick filaments and M-lines are two key components of the sarcomere.It has been suggested that myomesin proteins of M-lines interact with myosin and titin proteins and keep the thick and titin filaments in order.However,the function of myomesin in myofibrillogenesis and sarcomere organization remained largely enigmatic.No knockout or knockdown animal models have been reported to elucidate the role of myomesin in sarcomere organization in vivo.In this study,by using the gene-specific knockdown approach in zebrafish embryos,we carried out a loss-of-function analysis of myomesin-3 and slow myosin heavy chain l (smyhcl) expressed specifically in slow muscles.We demonstrated that knockdown of smyhcl abolished the sarcomeric localization of myomesin-3 in slow muscles.In contrast,loss of myomesin-3 had no effect on the sarcomeric organization of thick and thin filaments as well as M- and Z-line structures.Together,these studies indicate that myosin thick filaments are required for M-line organization and M-line localization of myomesin-3.In contrast,myomesin-3 is dispensable for sarcomere organization in slow muscles.

  16. Slow tourism jako nová forma cestovního ruchu

    OpenAIRE

    Pajmová, Klára

    2012-01-01

    The thesis is focused on slow tourism. The first chapter is dedicated to national and international documents governing sustainable development of tourism, impacts of tourism and approaches to sustainable tourism. It also defines slow tourism, presents the history of its origin, present and future position in the world tourism and the typical participant of slow tourism. Destination of slow tourism and requirements of slow tourists are characterized in this thesis. The next chapter deals with...

  17. DNA-binding residues and binding mode prediction with binding-mechanism concerned models

    OpenAIRE

    Oyang Yen-Jen; Liu Yu-Cheng; Huang Chun-Chin; Huang Yu-Feng; Huang Chien-Kang

    2009-01-01

    Abstract Background Protein-DNA interactions are essential for fundamental biological activities including DNA transcription, replication, packaging, repair and rearrangement. Proteins interacting with DNA can be classified into two categories of binding mechanisms - sequence-specific and non-specific binding. Protein-DNA specific binding provides a mechanism to recognize correct nucleotide base pairs for sequence-specific identification. Protein-DNA non-specific binding shows sequence indepe...

  18. Location and nature of calcium-binding sites in salivary acidic proline-rich phosphoproteins

    International Nuclear Information System (INIS)

    The location of the calcium-binding sites in the human acidic proline-rich proteins, salivary proteins A and C, was determined by equilibrium dialysis of the tryptic peptides with buffers containing 45Ca. All the calcium-binding sites are located in the NH2-terminal tryptic peptide (TX peptide). The nature of the calcium binding sites in the TX peptide and native salivary proteins A and C, as well as dephosphorylated proteins was compared. Two types of sites can be distinguished in peptide TX. Type I sites have an apparent dissociation constant (K) of 38 μM and are responsible for the binding of 2.6 mol of Ca/mol of peptide. The corresponding figures for Type II sites are 780 μM and 5.3 mol of Ca/mol of peptide. In the native proteins, the amount of calcium bound at the type II sites decreases to 3.9 mol of Ca/mol of proteins A and C and K increases to 1100 μM. The amount of calcium bound at type I sites decreases to 1.5 mol/mol of protein A and 0.6 mol/mol of protein C, but there is no change in K. Dephosphorylation affects the calcium binding at both types of sites. The experiments indicate that the COOH-terminal parts of the native proteins affect the number and the nature of the protein calcium-binding sites. Proton and phosphorous NMR data demonstrate that β-COOH in aspartic acid, as well as phosphoserine, are part of the calcium-binding sites. The difference in calcium binding to salivary proteins A and C may be due at least partially to differences in the environment of one or more aspartic acids

  19. Location and nature of calcium-binding sites in salivary acidic proline-rich phosphoproteins

    Energy Technology Data Exchange (ETDEWEB)

    Bennick, A. (Univ. of Toronto, Ontario); McLaughlin, A.C.; Grey, A.A.; Madapallimattam, G.

    1981-05-25

    The location of the calcium-binding sites in the human acidic proline-rich proteins, salivary proteins A and C, was determined by equilibrium dialysis of the tryptic peptides with buffers containing /sup 45/Ca. All the calcium-binding sites are located in the NH/sub 2/-terminal tryptic peptide (TX peptide). The nature of the calcium binding sites in the TX peptide and native salivary proteins A and C, as well as dephosphorylated proteins was compared. Two types of sites can be distinguished in peptide TX. Type I sites have an apparent dissociation constant (K) of 38 ..mu..M and are responsible for the binding of 2.6 mol of Ca/mol of peptide. The corresponding figures for Type II sites are 780 ..mu..M and 5.3 mol of Ca/mol of peptide. In the native proteins, the amount of calcium bound at the type II sites decreases to 3.9 mol of Ca/mol of proteins A and C and K increases to 1100 ..mu..M. The amount of calcium bound at type I sites decreases to 1.5 mol/mol of protein A and 0.6 mol/mol of protein C, but there is no change in K. Dephosphorylation affects the calcium binding at both types of sites. The experiments indicate that the COOH-terminal parts of the native proteins affect the number and the nature of the protein calcium-binding sites. Proton and phosphorous NMR data demonstrate that ..beta..-COOH in aspartic acid, as well as phosphoserine, are part of the calcium-binding sites. The difference in calcium binding to salivary proteins A and C may be due at least partially to differences in the environment of one or more aspartic acids.

  20. Carboplatin binding to histidine

    International Nuclear Information System (INIS)

    An X-ray crystal structure showing the binding of purely carboplatin to histidine in a model protein has finally been obtained. This required extensive crystallization trials and various novel crystal structure analyses. Carboplatin is a second-generation platinum anticancer agent used for the treatment of a variety of cancers. Previous X-ray crystallographic studies of carboplatin binding to histidine (in hen egg-white lysozyme; HEWL) showed the partial conversion of carboplatin to cisplatin owing to the high NaCl concentration used in the crystallization conditions. HEWL co-crystallizations with carboplatin in NaBr conditions have now been carried out to confirm whether carboplatin converts to the bromine form and whether this takes place in a similar way to the partial conversion of carboplatin to cisplatin observed previously in NaCl conditions. Here, it is reported that a partial chemical transformation takes place but to a transplatin form. Thus, to attempt to resolve purely carboplatin binding at histidine, this study utilized co-crystallization of HEWL with carboplatin without NaCl to eliminate the partial chemical conversion of carboplatin. Tetragonal HEWL crystals co-crystallized with carboplatin were successfully obtained in four different conditions, each at a different pH value. The structural results obtained show carboplatin bound to either one or both of the N atoms of His15 of HEWL, and this particular variation was dependent on the concentration of anions in the crystallization mixture and the elapsed time, as well as the pH used. The structural details of the bound carboplatin molecule also differed between them. Overall, the most detailed crystal structure showed the majority of the carboplatin atoms bound to the platinum centre; however, the four-carbon ring structure of the cyclobutanedicarboxylate moiety (CBDC) remained elusive. The potential impact of the results for the administration of carboplatin as an anticancer agent are described