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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. 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.

  3. Zinc ions bind to and inhibit activated protein C

    DEFF Research Database (Denmark)

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

    2010-01-01

    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...

  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...

  5. Determination of the critical residues responsible for cardiac myosin binding protein C's interactions.

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    Bhuiyan, Md Shenuarin; Gulick, James; Osinska, Hanna; Gupta, Manish; Robbins, Jeffrey

    2012-12-01

    Despite early demonstrations of myosin binding protein C's (MyBP-C) interaction with actin, different investigators have reached different conclusions regarding the relevant and necessary domains mediating this binding. Establishing the detailed structure-function relationships is needed to fully understand cMyBP-C's ability to impact on myofilament contraction as mutations in different domains are causative for familial hypertrophic cardiomyopathy. We defined cMyBP-C's N-terminal structural domains that are necessary or sufficient to mediate interactions with actin and/or the head region of the myosin heavy chain (S2-MyHC). Using a combination of genetics and functional assays, we defined the actin binding site(s) present in cMyBP-C. We confirmed that cMyBP-C's C1 and m domains productively interact with actin, while S2-MyHC interactions are restricted to the m domain. Using residue-specific mutagenesis, we identified the critical actin binding residues and distinguished them from the residues that were critical for S2-MyHC binding. To validate the structural and functional significance of these residues, we silenced the endogenous cMyBP-C in neonatal rat cardiomyocytes (NRC) using cMyBP-C siRNA, and replaced the endogenous cMyBP-C with normal or actin binding-ablated cMyBP-C. Replacement with actin binding-ablated cMyBP-C showed that the mutated protein did not incorporate into the sarcomere normally. Residues responsible for actin and S2-MyHC binding are partially present in overlapping domains but are unique. Expression of an actin binding-deficient cMyBP-C resulted in abnormal cytosolic distribution of the protein, indicating that interaction with actin is essential for the formation and/or maintenance of normal cMyBP-C sarcomeric distribution.

  6. In vivo definition of cardiac myosin-binding protein C's critical interactions with myosin.

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    Bhuiyan, Md Shenuarin; McLendon, Patrick; James, Jeanne; Osinska, Hanna; Gulick, James; Bhandary, Bidur; Lorenz, John N; Robbins, Jeffrey

    2016-10-01

    Cardiac myosin-binding protein C (cMyBP-C) is an integral part of the sarcomeric machinery in cardiac muscle that enables normal function. cMyBP-C regulates normal cardiac contraction by functioning as a brake through interactions with the sarcomere's thick, thin, and titin filaments. cMyBP-C's precise effects as it binds to the different filament systems remain obscure, particularly as it impacts on the myosin heavy chain's head domain, contained within the subfragment 2 (S2) region. This portion of the myosin heavy chain also contains the ATPase activity critical for myosin's function. Mutations in myosin's head, as well as in cMyBP-C, are a frequent cause of familial hypertrophic cardiomyopathy (FHC). We generated transgenic lines in which endogenous cMyBP-C was replaced by protein lacking the residues necessary for binding to S2 (cMyBP-C(S2-)). We found, surprisingly, that cMyBP-C lacking the S2 binding site is incorporated normally into the sarcomere, although systolic function is compromised. We show for the first time the acute and chronic in vivo consequences of ablating a filament-specific interaction of cMyBP-C. This work probes the functional consequences, in the whole animal, of modifying a critical structure-function relationship, the protein's ability to bind to a region of the critical enzyme responsible for muscle contraction, the subfragment 2 domain of the myosin heavy chain. We show that the binding is not critical for the protein's correct insertion into the sarcomere's architecture, but is essential for long-term, normal function in the physiological context of the heart.

  7. 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...

  8. Myosin binding protein C:Structural abnormalities in familial hypertrophic cardiomyopathy

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    The muscle protein myosin binding protein C (MyBPC) is a large multi-domain protein whose role in the sarcomere is complex and not yet fully understood. Mutations in MyBPC are strongly associated with the heart disease familial hypertrophic cardiomyopathy (FHC) and these experiments of nature have provided some insight into the intricate workings of this protein in the heart. While some regions of the MyBPC molecule have been assigned a function in the regulation of muscle contraction, the interaction of other regions with various parts of the myosin molecule and the sarcomeric proteins, actin and titin, remain obscure. In additic n, several intra-domain interactions between adjacent MyBPC molecules have been identified. Although the basic structure of the molecule (a series of immunoglobulin and fibronectin domains) has been elucidated, the assembly of MyBPC in the sarcomere is a topic for debate. By analysing the MyBPC sequence with respect to FHC-causing mutations it is possible to identify individual residues or regions of each domain that may be important either for binding or regulation. This review looks at the current literature, in concert with alignments and the structural models of MyBPC, in an attempt to understand how FHC mutations may lead to the disease state.

  9. 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...

  10. Phosphorylation and calcium antagonistically tune myosin-binding protein C's structure and function.

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    Previs, Michael J; Mun, Ji Young; Michalek, Arthur J; Previs, Samantha Beck; Gulick, James; Robbins, Jeffrey; Warshaw, David M; Craig, Roger

    2016-03-22

    During each heartbeat, cardiac contractility results from calcium-activated sliding of actin thin filaments toward the centers of myosin thick filaments to shorten cellular length. Cardiac myosin-binding protein C (cMyBP-C) is a component of the thick filament that appears to tune these mechanochemical interactions by its N-terminal domains transiently interacting with actin and/or the myosin S2 domain, sensitizing thin filaments to calcium and governing maximal sliding velocity. Both functional mechanisms are potentially further tunable by phosphorylation of an intrinsically disordered, extensible region of cMyBP-C's N terminus, the M-domain. Using atomic force spectroscopy, electron microscopy, and mutant protein expression, we demonstrate that phosphorylation reduced the M-domain's extensibility and shifted the conformation of the N-terminal domain from an extended structure to a compact configuration. In combination with motility assay data, these structural effects of M-domain phosphorylation suggest a mechanism for diminishing the functional potency of individual cMyBP-C molecules. Interestingly, we found that calcium levels necessary to maximally activate the thin filament mitigated the structural effects of phosphorylation by increasing M-domain extensibility and shifting the phosphorylated N-terminal fragments back to the extended state, as if unphosphorylated. Functionally, the addition of calcium to the motility assays ablated the impact of phosphorylation on maximal sliding velocities, fully restoring cMyBP-C's inhibitory capacity. We conclude that M-domain phosphorylation may have its greatest effect on tuning cMyBP-C's calcium-sensitization of thin filaments at the low calcium levels between contractions. Importantly, calcium levels at the peak of contraction would allow cMyBP-C to remain a potent contractile modulator, regardless of cMyBP-C's phosphorylation state.

  11. 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.

  12. 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...

  13. 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...

  14. 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.

  15. 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;

    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...

  16. 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 ...

  17. 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.

  18. Staphylococcus aureus Manganese Transport Protein C (MntC) Is an Extracellular Matrix- and Plasminogen-Binding Protein

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    Salazar, Natália; Castiblanco-Valencia, Mónica Marcela; da Silva, Ludmila Bezerra; de Castro, Íris Arantes; Monaris, Denize; Masuda, Hana Paula; Barbosa, Angela Silva; Arêas, Ana Paula Mattos

    2014-01-01

    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. PMID:25409527

  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. 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.

  1. 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;

    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....... Binding of these proteins to SAP was demonstrated when SAP was immobilized using F(ab')2 anti-SAP, but not when SAP reacted with these proteins in liquid phase; thus the binding to human SAP was markedly phase state dependent. Presaturation of solid phase SAP with heparin, which binds SAP with high...... 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...

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

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    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

  3. Lipopolysaccharide Binding Protein, Soluble-Intercellular Adhesion Molecule-1, Procalcitonin, and Protein C Activity and Clinical Outcome in Systemic Inflammatory Response Syndrome (SIRS or Sepsis Patients

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    Dewi Muliaty

    2009-04-01

    Full Text Available BACKGROUND: Biochemical markers may be used in diagnosis, prognostic and monitoring treatment and therapy for sepsis patients. In this study we used Lipopolysacharide Binding Protein (LBP, serum-Intercellular Adhesion Molecule-1 (ICAM-1, Procalcitonin (PCT and protein C activity. LBP is related to lipopolysachharide or gram-negative bacterial endotoxin which bound to LBP and induced inflammatory response. ICAM-1 is associated with endothelial dysfunction in response to systemic inflammatory and septic condition. PCT increased in bacterial infection and in severe systemic inflammatory. Role of Protein C is protecting the intravascular system to systemic inflammation, sepsis and the concomitant intravascular coagulopathy. The aim of this study was to examine the associations between levels of serum LBP, sICAM-1, PCT, and protein C activity with the clinical outcome of SIRS or sepsis patients. METHODS: We included 19 post surgery patients with SIRS criteria from intensive care unit (ICU and evaluated the level of LBP serum with Chemiliuminescent Enzyme Immunoassay (Diagnostic Product Co., ICAM-1 with ELISA (R&D System, PCT with immunochromatography (BRAHMS, protein C activity with chromogenic method (Dade Behring. We performed the samples serially at the first admission of patients and after 72 hours. Data were analysed by non-parametric with Wilcoxon test and Mann-Whitney test. Correlation study between biomarkers calculated by Kendall’s tau and Spearman’s rho. RESULTS: Of 19 patients, 9 (47,4% died and 10 (52,6% surviving. The level of LBP serum decreased after 72 hours in surviving-sepsis patients, and increased in nonsurviving sepsis patients with significant different levels at 72 hours examination (p0.05. In all patients were found high level of PCT serum since the first admission examination, decreasing levels were occurred significantly in surviving patients after 72 hours (p0.05 both in surviving and non-surviving patients. CONCLUSIONS

  4. Myocardial infarction-induced N-terminal fragment of cardiac myosin-binding protein C (cMyBP-C) impairs myofilament function in human myocardium.

    Science.gov (United States)

    Witayavanitkul, Namthip; Ait Mou, Younss; Kuster, Diederik W D; Khairallah, Ramzi J; Sarkey, Jason; Govindan, Suresh; Chen, Xin; Ge, Ying; Rajan, Sudarsan; Wieczorek, David F; Irving, Thomas; Westfall, Margaret V; de Tombe, Pieter P; Sadayappan, Sakthivel

    2014-03-28

    Myocardial infarction (MI) is associated with depressed cardiac contractile function and progression to heart failure. Cardiac myosin-binding protein C, a cardiac-specific myofilament protein, is proteolyzed post-MI in humans, which results in an N-terminal fragment, C0-C1f. The presence of C0-C1f in cultured cardiomyocytes results in decreased Ca(2+) transients and cell shortening, abnormalities sufficient for the induction of heart failure in a mouse model. However, the underlying mechanisms remain unclear. Here, we investigate the association between C0-C1f and altered contractility in human cardiac myofilaments in vitro. To accomplish this, we generated recombinant human C0-C1f (hC0C1f) and incorporated it into permeabilized human left ventricular myocardium. Mechanical properties were studied at short (2 μm) and long (2.3 μm) sarcomere length (SL). Our data demonstrate that the presence of hC0C1f in the sarcomere had the greatest effect at short, but not long, SL, decreasing maximal force and myofilament Ca(2+) sensitivity. Moreover, hC0C1f led to increased cooperative activation, cross-bridge cycling kinetics, and tension cost, with greater effects at short SL. We further established that the effects of hC0C1f occur through direct interaction with actin and α-tropomyosin. Our data demonstrate that the presence of hC0C1f in the sarcomere is sufficient to induce depressed myofilament function and Ca(2+) sensitivity in otherwise healthy human donor myocardium. Decreased cardiac function post-MI may result, in part, from the ability of hC0C1f to bind actin and α-tropomyosin, suggesting that cleaved C0-C1f could act as a poison polypeptide and disrupt the interaction of native cardiac myosin-binding protein C with the thin filament.

  5. C0 and C1 N-terminal Ig domains of myosin binding protein C exert different effects on thin filament activation.

    Science.gov (United States)

    Harris, Samantha P; Belknap, Betty; Van Sciver, Robert E; White, Howard D; Galkin, Vitold E

    2016-02-01

    Mutations in genes encoding myosin, the molecular motor that powers cardiac muscle contraction, and its accessory protein, cardiac myosin binding protein C (cMyBP-C), are the two most common causes of hypertrophic cardiomyopathy (HCM). Recent studies established that the N-terminal domains (NTDs) of cMyBP-C (e.g., C0, C1, M, and C2) can bind to and activate or inhibit the thin filament (TF). However, the molecular mechanism(s) by which NTDs modulate interaction of myosin with the TF remains unknown and the contribution of each individual NTD to TF activation/inhibition is unclear. Here we used an integrated structure-function approach using cryoelectron microscopy, biochemical kinetics, and force measurements to reveal how the first two Ig-like domains of cMyPB-C (C0 and C1) interact with the TF. Results demonstrate that despite being structural homologs, C0 and C1 exhibit different patterns of binding on the surface of F-actin. Importantly, C1 but not C0 binds in a position to activate the TF by shifting tropomyosin (Tm) to the "open" structural state. We further show that C1 directly interacts with Tm and traps Tm in the open position on the surface of F-actin. Both C0 and C1 compete with myosin subfragment 1 for binding to F-actin and effectively inhibit actomyosin interactions when present at high ratios of NTDs to F-actin. Finally, we show that in contracting sarcomeres, the activating effect of C1 is apparent only once low levels of Ca(2+) have been achieved. We suggest that Ca(2+) modulates the interaction of cMyBP-C with the TF in the sarcomere.

  6. 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

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

    DEFF Research Database (Denmark)

    Granstroem, S.; Godiksen, M. T. N.; Christiansen, M.;

    2015-01-01

    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......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.......7 years an additional 6.7% (11/165) of the cats developed HCM. Survival data could be obtained for 262 of the cats originally included, and among these 9.2% (24/262) died of causes that met the study criteria for cardiac death. In the homozygous group 80% (20/25) of cats included were diagnosed with HCM...

  8. 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

  9. 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.

  10. 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.

  11. 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...

  12. 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

  13. 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.

  14. The antiviral drug acyclovir is a slow-binding inhibitor of (D)-amino acid oxidase.

    Science.gov (United States)

    Katane, Masumi; Matsuda, Satsuki; Saitoh, Yasuaki; Sekine, Masae; Furuchi, Takemitsu; Koyama, Nobuhiro; Nakagome, Izumi; Tomoda, Hiroshi; Hirono, Shuichi; Homma, Hiroshi

    2013-08-20

    d-Amino acid oxidase (DAO) is a degradative enzyme that is stereospecific for d-amino acids, including d-serine and d-alanine, which are believed to be coagonists of the N-methyl-d-aspartate (NMDA) receptor. To identify a new class of DAO inhibitor(s) that can be used to elucidate the molecular details of the active site environment of DAO, manifold biologically active compounds of microbial origin and pre-existing drugs were screened for their ability to inhibit DAO activity, and several compounds were identified as candidates. One of these compounds, acyclovir (ACV), a well-known antiviral drug used for the treatment of herpesvirus infections, was characterized and evaluated as a novel DAO inhibitor in vitro. Analysis showed that ACV acts on DAO as a reversible slow-binding inhibitor, and interestingly, the time required to achieve equilibrium between DAO, ACV, and the DAO/ACV complex was highly dependent on temperature. The binding mechanism of ACV to DAO was investigated in detail by several approaches, including kinetic analysis, structural modeling of DAO complexed with ACV, and site-specific mutagenesis of an active site residue postulated to be involved in the binding of ACV. The results confirm that ACV is a novel, active site-directed inhibitor of DAO that can be a valuable tool for investigating the structure-function relationships of DAO, including the molecular details of the active site environment of DAO. In particular, it appears that ACV can serve as an active site probe to study the structural basis of temperature-induced conformational changes of DAO.

  15. ORF2 protein of porcine circovirus type 2 promotes phagocytic activity of porcine macrophages by inhibiting proteasomal degradation of complement component 1, q subcomponent binding protein (C1QBP) through physical interaction.

    Science.gov (United States)

    Choi, Chang-Yong; Oh, Hae-Na; Lee, Suk Jun; Chun, Taehoon

    2015-11-01

    Defining how each ORF of porcine circovirus type 2 (PCV2) manipulates the host immune system may be helpful to understand the disease progression of post-weaning multisystemic wasting syndrome. In this study, we demonstrated a direct interaction between the PCV2 ORF2 and complement component 1, q subcomponent binding protein (C1QBP) within the cytoplasm of host macrophages. The physical interaction between PCV2 ORF2 and C1QBP inhibited ubiquitin-mediated proteasomal degradation of C1QBP in macrophages. Increased stability of C1QBP by the interaction with PCV2 ORF2 further enhanced the phagocytic activity of porcine macrophages through the phosphoinositol 3-kinase signalling pathway. This may explain the molecular basis of how PCV2 ORF2 enhances the phagocytic activity of host macrophages.

  16. Possible role for water dissociation in the slow binding of phosphorus-containing transition-state-analogue inhibitors of thermolysin.

    Science.gov (United States)

    Bartlett, P A; Marlowe, C K

    1987-12-29

    A number of phosphonamidate and phosphonate tripeptide analogues have been studied as transition-state-analogue inhibitors of the zinc endopeptidase thermolysin. Those with the form Cbz-GlyP(Y)Leu-X [ZGP(Y)LX, X = NH2 or amino acid, Y = NH or O linkage] are potent (Ki = 9-760 nM for X = NH, 9-660 microM for X = O) but otherwise ordinary in their binding behavior, with second-order rate constants for association (kon) greater than 10(5) M-1 s-1. Those with the form Cbz-XP(Y)-Leu-Ala [ZXP(Y)LA,XP = alpha-substituted phosphorus amino acid analogue] are similarly potent (Ki for ZFPLA = 68 pM) but slow binding (kon less than or equal to 1300 M-1 s-1). Several kinetic mechanisms for slow binding behavior are considered, including two-step processes and those that require prior isomerization of inhibitor or enzyme to a rare form. The association rates of ZFPLA and ZFP(O)LA are first order in inhibitor concentration up to 1-2 mM, indicating that any loose complex along the binding pathway must have a dissociation constant above this value. The crystallographic investigation described in the preceding paper [Holden, H. M., Tronrud, D. E., Monzingo, A. F., Weaver, L. H., & Matthews, B. W. (1987) Biochemistry (preceding paper in this issue)] identifies a specific water molecule in the active site that may hinder binding of the alpha-substituted inhibitors. The implication of this observation for a mechanism for slow binding is discussed.

  17. Regulation of adipocyte 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1 by CCAAT/enhancer-binding protein (C/EBP β isoforms, LIP and LAP.

    Directory of Open Access Journals (Sweden)

    Cristina L Esteves

    Full Text Available 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1 catalyses intracellular regeneration of active glucocorticoids, notably in liver and adipose tissue. 11β-HSD1 is increased selectively in adipose tissue in human obesity, a change implicated in the pathogenesis of metabolic syndrome. With high fat (HF-feeding, adipose tissue 11β-HSD1 is down-regulated in mice, plausibly to counteract metabolic disease. Transcription of 11β-HSD1 is directly regulated by members of the CCAAT/enhancer binding protein (C/EBP family. Here we show that while total C/EBPβ in adipose tissue is unaltered by HF diet, the ratio of the C/EBPβ isoforms liver-enriched inhibitor protein (LIP and liver-enriched activator protein (LAP (C/EBPβ-LIP:LAP is increased in subcutaneous adipose. This may cause changes in 11β-HSD1 expression since genetically modified C/EBPβ((+/L mice, with increased C/EBPβ-LIP:LAP ratio, have decreased subcutaneous adipose 11β-HSD1 mRNA levels, whereas C/EBPβ(ΔuORF mice, with decreased C/EBPβ-LIP:LAP ratio, show increased subcutaneous adipose 11β-HSD1. C/EBPβ-LIP:LAP ratio is regulated by endoplasmic reticulum (ER stress and mTOR signalling, both of which are altered in obesity. In 3T3-L1 adipocytes, 11β-HSD1 mRNA levels were down-regulated following induction of ER stress by tunicamycin but were up-regulated following inhibition of mTOR by rapamycin. These data point to a central role for C/EBPβ and its processing to LIP and LAP in transcriptional regulation of 11β-HSD1 in adipose tissue. Down-regulation of 11β-HSD1 by increased C/EBPβ-LIP:LAP in adipocytes may be part of a nutrient-sensing mechanism counteracting nutritional stress generated by HF diet.

  18. 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.

  19. 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

  20. Rational Design of Highly Potent and Slow-Binding Cytochrome bc1 Inhibitor as Fungicide by Computational Substitution Optimization

    Science.gov (United States)

    Hao, Ge-Fei; Yang, Sheng-Gang; Huang, Wei; Wang, Le; Shen, Yan-Qing; Tu, Wen-Long; Li, Hui; Huang, Li-Shar; Wu, Jia-Wei; Berry, Edward A.; Yang, Guang-Fu

    2015-01-01

    Hit to lead (H2L) optimization is a key step for drug and agrochemical discovery. A critical challenge for H2L optimization is the low efficiency due to the lack of predictive method with high accuracy. We described a new computational method called Computational Substitution Optimization (CSO) that has allowed us to rapidly identify compounds with cytochrome bc1 complex inhibitory activity in the nanomolar and subnanomolar range. The comprehensively optimized candidate has proved to be a slow binding inhibitor of bc1 complex, ~73-fold more potent (Ki = 4.1 nM) than the best commercial fungicide azoxystrobin (AZ; Ki = 297.6 nM) and shows excellent in vivo fungicidal activity against downy mildew and powdery mildew disease. The excellent correlation between experimental and calculated binding free-energy shifts together with further crystallographic analysis confirmed the prediction accuracy of CSO method. To the best of our knowledge, CSO is a new computational approach to substitution-scanning mutagenesis of ligand and could be used as a general strategy of H2L optimisation in drug and agrochemical design.

  1. 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...

  2. Distinct Ca2+ and Sr2+ binding properties of synaptotagmins. Definition of candidate Ca2+ sensors for the fast and slow components of neurotransmitter release.

    Science.gov (United States)

    Li, C; Davletov, B A; Südhof, T C

    1995-10-20

    Ca(2+)-dependent neurotransmitter release consists of at least two components: a major fast component that is insensitive to Sr2+ and a minor slow component that is potentiated by Sr2+ (Goda, Y., and Stevens, C. F. (1994) Proc. Natl. Acad. U. S. A. 91, 12942-12946). These results suggest that at least two Ca2+ sensors act in synaptic vesicle fusion with distinct Ca2+ and Sr2+ binding properties. We have now investigated the relative Ca2+ and Sr2+ binding activities of synaptotagmins to evaluate their potential roles as Ca2+ sensors for the fast and slow components. Our results demonstrate that the first C2 domains of synaptotagmins I, II, III, V, and VII have very similar Ca2+ requirements for phospholipid binding (range of EC50 = 2.6 microM to 5.0 microM), but distinct Sr2+ requirements (EC50 range = 23 microM to 133 microM); synaptotagmins I and II had the lowest Sr2+ affinity, and synaptotagmin III the highest Sr2+ affinity. Purified synaptotagmin I from bovine brain exhibited similar properties as its recombinant first C2 domain, suggesting that the first C2 domain fully accounts for its Ca(2+)-dependent phospholipid binding properties. Sr2+ was unable to trigger syntaxin binding by synaptotagmin I at all concentrations tested, whereas it was effective for synaptotagmin III. These results suggest that different C2 domains have distinct Sr2+ binding properties. They support the hypothesis that synaptotagmins localized on the same vesicle perform distinct functions, with synaptotagmins I and II serving as candidate Ca2+ sensors for the fast component in release and synaptotagmin III for the slow component.

  3. Phosphorylation of thymidylate synthase affects slow-binding inhibition by 5-fluoro-dUMP and N(4)-hydroxy-dCMP.

    Science.gov (United States)

    Ludwiczak, Jan; Maj, Piotr; Wilk, Piotr; Frączyk, Tomasz; Ruman, Tomasz; Kierdaszuk, Borys; Jarmuła, Adam; Rode, Wojciech

    2016-04-01

    Endogenous thymidylate synthases, isolated from tissues or cultured cells of the same specific origin, have been reported to show differing slow-binding inhibition patterns. These were reflected by biphasic or linear dependence of the inactivation rate on time and accompanied by differing inhibition parameters. Considering its importance for chemotherapeutic drug resistance, the possible effect of thymidylate synthase inhibition by post-translational modification was tested, e.g. phosphorylation, by comparing sensitivities to inhibition by two slow-binding inhibitors, 5-fluoro-dUMP and N(4)-hydroxy-dCMP, of two fractions of purified recombinant mouse enzyme preparations, phosphorylated and non-phosphorylated, separated by metal oxide/hydroxide affinity chromatography on Al(OH)3 beads. The modification, found to concern histidine residues and influence kinetic properties by lowering Vmax, altered both the pattern of dependence of the inactivation rate on time from linear to biphasic, as well as slow-binding inhibition parameters, with each inhibitor studied. Being present on only one subunit of at least a great majority of phosphorylated enzyme molecules, it probably introduced dimer asymmetry, causing the altered time dependence of the inactivation rate pattern (biphasic with the phosphorylated enzyme) and resulting in asymmetric binding of each inhibitor studied. The latter is reflected by the ternary complexes, stable under denaturing conditions, formed by only the non-phosphorylated subunit of the phosphorylated enzyme with each of the two inhibitors and N(5,10)-methylenetetrahydrofolate. Inhibition of the phosphorylated enzyme by N(4)-hydroxy-dCMP was found to be strongly dependent on [Mg(2+)], cations demonstrated previously to also influence the activity of endogenous mouse TS isolated from tumour cells.

  4. The protein C pathway in cancer metastasis.

    Science.gov (United States)

    Spek, C Arnold; Arruda, Valder R

    2012-04-01

    Cancer is frequently associated with activation of blood coagulation, which in turn has been suggested to promote tumor growth and metastasis. Indeed, low molecular weight heparin treatment significantly prolongs the survival of a wide variety of patients with cancer. Based on this notion that anticoagulant treatment seems to benefit cancer patients, recent experiments aimed to elucidate the importance of the natural anticoagulant protein C pathways in cancer progression. Interestingly, these experiments showed that the repeated administration of exogenous activated protein C limits cancer cell extravasation in experimental animal models. In line, reducing endogenous activated protein C activity dramatically increased the number of experimental metastasis. These data thus strongly suggest that exogenous activated protein C administration may be a novel therapeutic avenue to limit cancer metastasis thereby prolonging overall survival of cancer patients. The current review provides an overview of recent data on the role of the protein C pathway in cancer metastasis. It discusses the potential of activated protein C as a novel target to reduce cancer progression, it points to several limitations of activated protein C administration in the setting of cancer cell metastasis and it suggest zymogen protein C as an attractive alternative. PMID:22682140

  5. 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

  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. 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

  8. 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

  9. 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

  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...... are possible contributors to the pathogenesis of pulmonary alveolar proteinosis. Molecular dynamics simulations using the NAMD2 package were performed for systems containing from one to seven SP-C molecules to study their behavior in water. The results of our simulations show that unfolding of the protein...

  11. 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.

  12. Protein C activity in dogs envenomed by Vipera palaestinae.

    Science.gov (United States)

    Hadar, Gil; Kelmer, Efrat; Segev, Gilad; Bruchim, Yaron; Aroch, Itamar

    2014-09-01

    Vipera palaestinae is responsible for most envenomations in humans and domestic animal in Israel. Its venom has pro- and anticoagulant properties. Protein C is a major natural anticoagulant, preventing excess clotting and thrombosis. This study investigated protein C activity and its prognostic value, as well as several other hemostatic analytes in dogs (Canis familiaris) accidently envenomed by V. palaestinae. Protein C activity was compared between envenomed dogs and 33 healthy control dogs. Mean protein C was lower in dogs envenomed by V. palaestinae compared to controls (12.9% vs. 22.9%, respectively; P Dogs diagnosed with consumptive coagulopathy (14%) tended to have lower protein C activity compared to others; however, their mortality did differ from that of other dogs. This is the first study assessing protein C activity in V. palaestinae victims. Decreased protein C activity in such dogs may play a role in formation of thrombosis and hemostatic derangement as well as inflammation in V. palaestinae envenomations.

  13. Activated protein C to heal pressure ulcers.

    Science.gov (United States)

    Wijewardena, Aruna; Lajevardi, Sepehr S; Vandervord, Elle; Vandervord, John; Lang, Thomas C; Fulcher, Gregory; Jackson, Christopher J

    2016-10-01

    Pressure ulcers present a major clinical challenge, are physically debilitating and place the patient at risk of serious comorbidities such as septic shock. Recombinant human activated protein C (APC) is an anticoagulant with anti-inflammatory, cytoprotective and angiogenic effects that promote rapid wound healing. Topical negative pressure wound therapy (TNP) has become widely used as a treatment modality in wounds although its efficacy has not been proven through randomised controlled trials. The aim of this study was to determine the preliminary efficacy and safety of treatment with APC for severe chronic pressure sores with and without TNP. This case presentation describes the history, management and outcome of two patients each with a severe chronic non-healing pressure ulcer that had failed to respond to conventional therapy. TNP was added to conservative management of both ulcers with no improvement seen. Then local application of small doses of APC was added to TNP and with conservative management, resulted in significant clinical improvement and rapid healing of both ulcers, displaying rapid growth of vascular granulation tissue with subsequent epithelialisation. Patients tolerated the treatment well and improvements suggested by long-term follow-up were provided. Randomised placebo-controlled double blind trials are needed to quantify the efficacy, safety, cost-effectiveness, optimal dose and quality of life changes seen from treatment with APC.

  14. Regulation of protein C inhibitor (PCI) activity by specific oxidized and negatively charged phospholipids.

    Science.gov (United States)

    Malleier, Julia M; Oskolkova, Olga; Bochkov, Valery; Jerabek, Ingrid; Sokolikova, Barbora; Perkmann, Thomas; Breuss, Johannes; Binder, Bernd R; Geiger, Margarethe

    2007-06-01

    Protein C inhibitor (PCI) is a serpin with affinity for heparin and phosphatidylethanolamine (PE). We analyzed the interaction of PCI with different phospholipids and their oxidized forms. PCI bound to oxidized PE (OxPE), and oxidized and unoxidized phosphatidylserine (PS) immobilized on microtiter plates and in aqueous suspension. Binding to OxPE and PS was competed by heparin, but not by the aminophospholipid-binding protein annexin V or the PCI-binding lipid retinoic acid. PS and OxPE stimulated the inhibition of activated protein C (aPC) by PCI in a Ca(++)-dependent manner, indicating that binding of both, aPC (Ca(++) dependent) and PCI (Ca(++) independent), to phospholipids is necessary. A peptide corresponding to the heparin-binding site of PCI abolished the stimulatory effect of PS on aPC inhibition. No stimulatory effect of phospholipids on aPC inhibition was seen with a PCI mutant lacking the heparin-binding site. A heparin-like effect of phospholipids (OxPE) was not seen with antithrombin III, another heparin-binding serpin, suggesting that it is specific for PCI. PCI and annexin V were found to be endogenously colocalized in atherosclerotic plaques, supporting the hypothesis that exposure of oxidized PE and/or PS may be important for the local regulation of PCI activity in vivo.

  15. 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

  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. 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

  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.

  19. Haplotypes of the endothelial protein C receptor (EPCR) gene are not associated with severe malaria in Tanzania

    DEFF Research Database (Denmark)

    Hansson, Helle Holm; Turner, Louise; Møller, Line;

    2015-01-01

    BACKGROUND: Endothelial protein C receptor (EPCR) was recently identified as a key receptor for Plasmodium falciparum erythrocyte membrane protein 1 mediating sequestration of P. falciparum-infected erythrocytes in patients suffering from severe malaria. Soluble EPCR (sEPCR) inhibits binding of P...

  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. 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.

  2. 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.

  3. The role of activated protein C in cancer progression

    NARCIS (Netherlands)

    G.L. van Sluis; H.R. Büller; C.A. Spek

    2010-01-01

    Activated protein C (APC) is best known as a natural anticoagulant that also has direct cell signaling properties which (among others) enhance vascular barrier function. We recently established the relevance of APC-induced barrier enhancement by showing that endogenous APC limits cancer cell extrava

  4. 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

  5. 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...

  6. 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

  7. 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.

  8. BALB/C鼠睾丸组织中冷诱导RNA结合蛋白的cDNA克隆与序列分析%Cloning and Sequence Analysis of Cold Inducible RNA-binding Protein cDNA from Testis Tissue in BALB/C Mice

    Institute of Scientific and Technical Information of China (English)

    金福厚; 庞岩; 李士泽; 杨焕民; 计红; 赵巧香; 尹位

    2009-01-01

    冷诱导RNA结合蛋白(Cold inducible RNA-binding protein,CIRP)在多种冷应激细胞(包括重组中国仓鼠卵巢细胞)中被发现.迄今为止,冷应激对活体生物基凶表达的影响还未见报道.和细胞相比,生物体具有更加复杂的冷应激调节机制.本研究以冷处理的BALB/C鼠为实验动物,从其睾丸组织巾克隆出了CIRP的cDNA.结果表明,CIRP在生物体中能够被低温诱导,可能防止生物体遭受冷损伤.根据克隆的cDNA所推测的氨基酸序列与GenBank上公布的小鼠、大鼠、人类、牛蛙、美西螈、非洲爪蟾胚胎细胞和卵母细胞的CIRP氨基酸序列同源性分别为100%、99.40%、95.5%、67.4%、58.4%、76.9%和79.1%.这表明CIRP在生物进化过程中是高度保守的,可能具有多种生理功能.因此,这一研究将为探索人类和动物冷应激分子机制创立系统试验模型和奠定新的实践基础.图5参14%The cold-inducible RNA-binding protein (CIRP) was found in various cells including recombinant Chinese hamster ovary (rCHO) cells under cold stress. However, the effect of cold stress on the gene expression of the intravital animals has not been reported till now. Compared with their cells, there were much more complicated regulatory mechanisms for cold stress response in the organisms. The BALB/C mice with cold treatment were used as experimental animals for this study. The cDNA of CIRP was firstly cloned from the testis tissues of the BALB/C mice treated by cold stress. The results indicated that CIRP in the organisms could be induced at low temperature and might protect the organisms from the cold damage. The amino acid sequences deduced via cDNA clone were 100%, 99.4%, 95.5%, 67.4%, 58.4%,76.9%, and 79.1% identical to those of the CIRP in mice, rats, human, bullfrog and axolotl cells, and Xenopus embryos and oocytes, respectively. These results show that the CIRP is highly conserved in the evolution process and may be involved in various

  9. 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

  10. 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...... not 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...

  11. 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.)

  12. 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.

  13. 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.

  14. 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

  15. [Protein C deficiency in black African with venous thromboembolism in Cotonou, Benin].

    Science.gov (United States)

    Houénassi, D M; Bigot, A; Tchabi, Y; Vehounkpé-Sacca, J; Akindes-Dossou Yovo, R; Gbaguidi, L; d'Almeida-Massougbodji, M; Agboton, H

    2013-02-01

    The aim of this study is to evaluate the frequency of protein C deficiency in venous thromboembolism in black African patients of Benin. It is a descriptive study. Inclusion criteria were: acceptance- having a venous thromboembolism. No exlusion criteria was retained. Protein C deficiency was diagnosed by quantitative technic with a Minividas materiel in the blood. Protein C dosage has been done before antivitamin k therapy and a second dosage has been done if the first one demonstrated a low level of protein C. Acuired aetiology have been research. For the 54 patients of this study mean age was 52.7±14.1 and sex-ratio 1.08. The frequency of protein C deficiency was 9.3% in all patients and 12.5% in those with clinical thrombophily (p=1). No acquired deficit has been found.

  16. 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.

  17. 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)

  18. 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

  19. Slow light beam splitter.

    Science.gov (United States)

    Xiao, Yanhong; Klein, Mason; Hohensee, Michael; Jiang, Liang; Phillips, David F; Lukin, Mikhail D; Walsworth, Ronald L

    2008-07-25

    We demonstrate a slow light beam splitter using rapid coherence transport in a wall-coated atomic vapor cell. We show that particles undergoing random and undirected classical motion can mediate coherent interactions between two or more optical modes. Coherence, written into atoms via electromagnetically induced transparency using an input optical signal at one transverse position, spreads out via ballistic atomic motion, is preserved by an antirelaxation wall coating, and is then retrieved in outgoing slow light signals in both the input channel and a spatially-separated second channel. The splitting ratio between the two output channels can be tuned by adjusting the laser power. The slow light beam splitter may improve quantum repeater performance and be useful as an all-optical dynamically reconfigurable router.

  20. 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...

  1. N-glycans of human protein C inhibitor: tissue-specific expression and function.

    Directory of Open Access Journals (Sweden)

    Wei Sun

    Full Text Available Protein C inhibitor (PCI is a serpin type of serine protease inhibitor that is found in many tissues and fluids in human, including blood plasma, seminal plasma and urine. This inhibitor displays an unusually broad protease specificity compared with other serpins. Previous studies have shown that the N-glycan(s and the NH₂-terminus affect some blood-related functions of PCI. In this study, we have for the first time determined the N-glycan profile of seminal plasma PCI, by mass spectrometry. The N-glycan structures differed markedly compared with those of both blood-derived and urinary PCI, providing evidence that the N-glycans of PCI are expressed in a tissue-specific manner. The most abundant structure (m/z 2592.9 had a composition of Fuc₃Hex₅HexNAc₄, consistent with a core fucosylated bi-antennary glycan with terminal Lewis(x. A major serine protease in semen, prostate specific antigen (PSA, was used to evaluate the effects of N-glycans and the NH₂-terminus on a PCI function related to the reproductive tract. Second-order rate constants for PSA inhibition by PCI were 4.3±0.2 and 4.1±0.5 M⁻¹ s⁻¹ for the natural full-length PCI and a form lacking six amino acids at the NH₂-terminus, respectively, whereas these constants were 4.8±0.1 and 29±7 M⁻¹ s⁻¹ for the corresponding PNGase F-treated forms. The 7-8-fold higher rate constants obtained when both the N-glycans and the NH₂-terminus had been removed suggest that these structures jointly affect the rate of PSA inhibition, presumably by together hindering conformational changes of PCI required to bind to the catalytic pocket of PSA.

  2. N-glycans of Human Protein C Inhibitor: Tissue-Specific Expression and Function

    Science.gov (United States)

    Engström, Åke; Sooriyaarachchi, Sanjeewani; Ubhayasekera, Wimal; Hreinsson, Julius; Wånggren, Kjell; Clark, Gary F.; Dell, Anne; Schedin-Weiss, Sophia

    2011-01-01

    Protein C inhibitor (PCI) is a serpin type of serine protease inhibitor that is found in many tissues and fluids in human, including blood plasma, seminal plasma and urine. This inhibitor displays an unusually broad protease specificity compared with other serpins. Previous studies have shown that the N-glycan(s) and the NH2-terminus affect some blood-related functions of PCI. In this study, we have for the first time determined the N-glycan profile of seminal plasma PCI, by mass spectrometry. The N-glycan structures differed markedly compared with those of both blood-derived and urinary PCI, providing evidence that the N-glycans of PCI are expressed in a tissue-specific manner. The most abundant structure (m/z 2592.9) had a composition of Fuc3Hex5HexNAc4, consistent with a core fucosylated bi-antennary glycan with terminal Lewisx. A major serine protease in semen, prostate specific antigen (PSA), was used to evaluate the effects of N-glycans and the NH2-terminus on a PCI function related to the reproductive tract. Second-order rate constants for PSA inhibition by PCI were 4.3±0.2 and 4.1±0.5 M−1s−1 for the natural full-length PCI and a form lacking six amino acids at the NH2-terminus, respectively, whereas these constants were 4.8±0.1 and 29±7 M−1s−1 for the corresponding PNGase F-treated forms. The 7–8-fold higher rate constants obtained when both the N-glycans and the NH2-terminus had been removed suggest that these structures jointly affect the rate of PSA inhibition, presumably by together hindering conformational changes of PCI required to bind to the catalytic pocket of PSA. PMID:22205989

  3. Human protein C: new preparations. Effective replacement therapy for some clotting disorders.

    Science.gov (United States)

    2003-02-01

    (1) Depending on its severity, congenital protein C deficiency can cause a variety of problems, such as increasing the frequency of venous thrombosis in high risk situations; recurrent venous thrombosis; skin necrosis at the start of treatment with a vitamin K antagonist; and severe thrombotic events in neonates. For many years the only available replacement treatment consisted of fresh frozen plasma which, among other adverse effects, carries a risk of hypervolemia. (2) Two human protein C concentrates prepared from donated blood have been given marketing authorisation in Europe for intravenous replacement therapy (Ceprotin from Baxter, and Protexel from LFB). (3) Their clinical files contain only retrospective case series (22 children with severe deficiency treated with Ceprotin; and 10 patients of various ages and with different degrees of severity treated with Protexel). The two preparations have not been compared with each other. (4) In patients with severe protein C deficiency, including neonates, replacement therapy with human protein C is effective, especially for treating cutaneous thrombosis and preventing thrombosis in high risk situations. (5) In patients with moderate deficiency, a short-course of human protein C prophylaxis reduces the frequency of thrombosis in high risk situations. (6) In long-term prophylaxis, human protein C replacement therapy, added to ongoing (but inadequately effective) vitamin K antagonist therapy, seems to reduce the risk of recurrent venous thrombosis even though it has some constraints. (7) The adverse effects of the two preparations are poorly documented. Allergic reactions and bleeding have been reported. Human protein C is a blood product, and therefore carries a risk of infection. (8) Ceprotin offers a small advantage, being available in two dose strengths: for a given dose the volume injected is halved. (9) In practice, Ceprotin and Protexel are the reference drugs for replacement therapy of constitutional protein C

  4. 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...

  5. 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.

  6. Molecular dynamics and docking simulation of a natural variant of Activated Protein C with impaired protease activity: implications for integrin-mediated antiseptic function.

    Science.gov (United States)

    D'Ursi, Pasqualina; Orro, Alessandro; Morra, Giulia; Moscatelli, Marco; Trombetti, Gabriele; Milanesi, Luciano; Rovida, Ermanna

    2015-01-01

    Activated Protein C (APC) is a multifunctional serine protease, primarily known for its anticoagulant function in the coagulation system. Several studies have already elucidated its role in counteracting apoptosis and inflammation in cells, while significant effort is still ongoing for defining its involvement in sepsis. Earlier literature has shown that the antiseptic function of APC is mediated by its binding to leukocyte integrins, which is due to the presence of the integrin binding motif Arg-Gly-Asp at the N-terminus of the APC catalytic chain. Many natural mutants have been identified in patients with Protein C deficiency diagnosis including a variant of specificity pocket (Gly216Asp). In this work, we present a molecular model of the complex of APC with αVβ3 integrin obtained by protein-protein docking approach. A computational analysis of this variant is hereby presented, based on molecular dynamics and docking simulations, aiming at investigating the effects of the Gly216Asp mutation on the protein conformation and inferring its functional implications. Our study shows that such mutation is likely to impair the protease activity while preserving the overall protein fold. Moreover, superposition of the integrin binding motifs in wild-type and mutant forms suggests that the interaction with integrin can still occur and thus the mutant is likely to retain its antiseptic function related to the neutrophyl integrin binding. Therapeutic applications could result in this APC mutant which retains antiseptic function without anticoagulant side effects.

  7. 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

  8. 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...

  9. 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

  10. Biochemical activity and gene analysis of inherited protein C and antithrombin deficiency in two Chinese pedigrees

    Institute of Scientific and Technical Information of China (English)

    周荣富; 傅启华; 王文斌; 谢爽; 胡翊群; 王学锋; 王振义; 王鸿利

    2004-01-01

    Background We identified the gene mutations in two Chinese pedigree of type Ⅰ hereditary protein C deficiency and type Ⅰ hereditary antithrombin deficiency.Methods The plasma level of protein C activity (PC∶ A), protein C antigen (PC∶ Ag) , protein S activity, antithrombin activity (AT∶ A) and antithrombin antigen (AT∶ Ag) of propositi and two family members were detected using ELISA and chromogenic assay, respectively. All exons and intron-exon boundaries of protein C gene and antithrombin gene were analyzed by direct sequencing of the corresponding amplified PCR products in DNA from the propositus. Results The plasma PC∶ A and PC∶ Ag of propositus 1 was 26% and 1.43 mg/dl, respectively. The PC∶ Ag and PC∶ A of his father were normal. The decreased PC∶ A level was seen in his mother and 4 of his maternal pedigree. PS∶ A and AT∶ A were all normal in pedigree 1 members. A C5498T heterozygous mutation in exon 3 of protein C gene, resulting in the substitution of Arg for Trp at the 15th amino acid, was identified in propositus 1 and 8 of his relatives. The plasma AT∶ A and AT∶ Ag of propositus 2 was 48.6% and 10.4 mg/dl, respectively. The reduced AT∶ A and AT∶ Ag levels were found in his father and 5 of paternal pedigree. PC∶ A, PC∶ Ag and PS∶ A were all in normal range. A heterozygous 13387-9G deletion in exon 6 of antithrombin gene was identified in propositus 2. This mutation introduced a frameshift and a premature stop at codon 426 and existed in 6 members of pedigree 2.Conclusion The C5498T heterozygous mutation in exon 3 of protein C gene, first reported in China, leads to type I hereditary protein C deficiency. The 13387-9G deletion, a novel mutation, can cause antithrombin deficiency and thrombosis.

  11. Anticoagulant synergism of heparin and activated protein C in vitro. Role of a novel anticoagulant mechanism of heparin, enhancement of inactivation of factor V by activated protein C.

    OpenAIRE

    Petäjä, J; Fernández, J. A.; Gruber, A.; Griffin, J H

    1997-01-01

    Interactions between standard heparin and the physiological anticoagulant plasma protein, activated protein C (APC) were studied. The ability of heparin to prolong the activated partial thromboplastin time and the factor Xa- one-stage clotting time of normal plasma was markedly enhanced by addition of purified APC to the assays. Experiments using purified clotting factors showed that heparin enhanced by fourfold the phospholipid-dependent inactivation of factor V by APC. In contrast to factor...

  12. 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.

  13. 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.

  14. 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:

  15. 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.

  16. 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...

  17. Protein C activation during the initial phase of experimental acute pancreatitis in the rabbit

    DEFF Research Database (Denmark)

    Ottesen, L H; Bladbjerg, E-M; Osman, M;

    2000-01-01

    activity), anticoagulant proteins (protein C, antithrombin) and fibrinolytic factors (tissue plasminogen activator, plasminogen activator inhibitor-1) were performed for 5 h. RESULTS: ANP was confirmed by elevated serum amylase, development of ascites, and histological changes of the pancreas. A moderate...... of the lungs or kidneys was found in 2 rabbits with ANP. CONCLUSION: An immediate activation of protein C is a specific characteristic of the haemostatic activation in ANP in rabbits. This activation has not been described previously and the possible therapeutic implications ought to be studied....

  18. The use of activated protein C in severe Plasmodium falciparum malaria.

    Science.gov (United States)

    Rankin, L G; Austin, D L H

    2007-06-01

    A 56-year-old man presented to a peripheral hospital in New Zealand with severe Plasmodium falciparum malaria with cerebral involvement and subsequently developed multi-system organ failure. Activated protein C was used in an attempt to stop the cascade of events into multi-organ failure. Severe infection with P. falciparum is life-threatening and appears to activate a hypercoagulable state similar to that of severe sepsis. Activated protein C is currently used in the treatment of severe sepsis and may provide a new adjuvant therapy for severe P. falciparum malaria.

  19. Slow change deafness.

    Science.gov (United States)

    Neuhoff, John G; Wayand, Joseph; Ndiaye, Mamoudou C; Berkow, Ann B; Bertacchi, Breanna R; Benton, Catherine A

    2015-05-01

    In four experiments, we demonstrated a new phenomenon called "slow-change deafness." In Experiment 1 we presented listeners with continuous speech that changed three semitones in pitch over time, and we found that nearly 50 % failed to notice the change. Experiments 2 and 3 replicated the finding, demonstrated that the changes in the stimuli were well above threshold, and showed that when listeners were alerted to the possibility of a change, detection rates improved dramatically. Experiment 4 showed that increasing the magnitude of the change that occurred in the stimulus decreased the rate of change deafness. Our results are consistent with previous work that had shown that cueing listeners to potential auditory changes can significantly reduce change deafness. These findings support an account of change deafness that is dependent on both the magnitude of a stimulus change and listener expectations.

  20. 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.

  1. 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;

    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....

  2. Inflammation-associated activation of coagulation and immune regulation by the protein C pathway.

    Science.gov (United States)

    Weiler, Hartmut

    2014-05-01

    The inflammation-induced activation of the protein C pathway provides negative feedback inhibition of coagulation and exerts coagulation-independent anti-inflammatory and cytoprotective effects. The balance between these activities of aPC modulates the outcome of diverse inflammatory diseases such as encephalitis, diabetes, and sepsis; and is affected by naturally occurring aPC-resistance of coagulation factor V Leiden.

  3. Circulating nucleosomes and severity of illness in children suffering from meningococcal sepsis treated with protein C

    NARCIS (Netherlands)

    Zeerleder, Sacha; Stephan, Femke; Emonts, Marieke; de Kleijn, Ester D.; Esmon, Charles T.; Varadi, Katalin; Hack, Cornelis Erik; Hazelzet, Jan A.

    2012-01-01

    Objective: Cell death leading to circulating nucleosomes and histones is a critical step in the pathogenesis of sepsis and contributes to lethality. Activated protein C was demonstrated to attenuate the harmful effects of histones. The objective of this retrospective study was to evaluate whether nu

  4. Activated Protein C Protects Against Myocardial Ischemia/Reperfusion Injury via Inhibition of Apoptosis and Inflammation

    NARCIS (Netherlands)

    S.T.B.G. Loubele; C.A. Spek; P. Leenders; R. van Oerle; H.L. Aberson; K. Hamulyák; G. Ferrell; C.T. Esmon; H.M.H. Spronk; H. ten Cate

    2009-01-01

    Objective-In spite of major advances in reperfusion therapy for patients presenting with acute coronary syndrome, long-term morbidity is still substantial. A limitation of initial treatment of myocardial ischemia is the lack of prevention of ischemia/reperfusion (I/R) injury. Activated protein C (AP

  5. 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

  6. Protein C and/or S deficiency presenting as peripheral arterial insufficiency.

    Science.gov (United States)

    Cho, Y P; Kwon, T-W; Ahn, J-H; Kang, G H; Han, M S; Kim, Y H; Kwak, J H; Lee, S G

    2005-07-01

    Although protein C and/or S deficiency has frequently been associated with venous thromboembolic events, instances of arterial thromboses have been reported. However, the exact incidence of protein C and/or S deficiency in patients with peripheral arterial insufficiency has not been established. Furthermore, given the lack of adequate studies to define the natural history and angiographic findings of these patients, the treatment has not been well delineated. Therefore, we conducted a prospective study to investigate the prevalence, characteristic angiographic findings and optimal treatments in patients with peripheral arterial insufficiency associated with protein C and/or S deficiency. Between September 2000 and August 2004, 133 patients who presented with peripheral arterial insufficiency underwent hypercoagulability tests before the initiation of any treatments. Of these, 11 patients (8.3%) with protein C and/or S deficiency were included in this study. There were nine males and two females. The ages ranged from 38 years to 72 years (mean 57 years). All patients showed characteristic angiographic findings: long segment thrombotic occlusion of a main peripheral artery without evidence of atherosclerosis or with mild atherosclerotic changes in the aorta and other major arterial trees. Surgical or endovascular procedures were performed in nine patients: bypass graft in four, thrombectomy in four and catheter-directed thrombolysis in one. Conservative treatment with full anticoagulation was performed in two patients. All patients received pre- and post-operative anticoagulation. Except for one amputated case, clinical and vascular laboratory improvements were achieved in 10 patients. Mean follow-up period was 21 months (range 4-45 months). However, one patient, in whom re-vascularization surgery was performed successfully, discontinued warfarin therapy himself at 10 months after surgery, graft occlusion and limb loss occurred at 30 months after surgery. This

  7. 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

  8. Mortality Risk of Untreated Myosin-Binding Protein C-Related Hypertrophic Cardiomyopathy Insight Into the Natural History

    NARCIS (Netherlands)

    Nannenberg, Eline A.; Michels, Michelle; Christiaans, Imke; Majoor-Krakauer, Danielle; Hoedemaekers, Yvonne M.; van Tintelen, J. Peter; Lombardi, M. Paola; ten Cate, Folkert J.; Schinkel, Arend F. L.; Tijssen, Jan G. P.; van Langen, Irene M.; Wilde, Arthur A. M.; Sijbrands, Eric J. G.

    2011-01-01

    Objectives 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. Background HCM is feared for the risk of sudden cardiac death (SCD). Insight in the natural history of the disorder is

  9. 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...

  10. 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...

  11. Acquired protein C deficiency in a child with acute myelogenous leukemia, splenic, renal, and intestinal infarction.

    Science.gov (United States)

    Farah, Roula A; Jalkh, Khalil S; Farhat, Hussein Z; Sayad, Paul E; Kadri, Adel M

    2011-03-01

    We report the case of a 6-year-old boy diagnosed with acute promyelocytic leukemia (AML-M3V) when he presented with pallor, abdominal pain, anorexia, and fatigue. Induction chemotherapy was started according to the AML-BFM 98 protocol along with Vesanoid (ATRA, All-trans retinoic acid). On the sixth day of induction, he developed splenic and gallbladder infarcts. Splenectomy and cholecystectomy were performed while chemotherapy induction continued as scheduled. Four days later, he developed ischemic areas in the kidneys and ischemic colitis in the sigmoid colon. Hypercoagulation studies showed severe deficiency of protein C. Tests showed protein C 16% (reference range 70-140%), protein S 87% (reference range 70-140%), antithrombin III 122% (reference range 80-120%), prothrombin time 13.6 s (reference = 11.3), INR (international normalized ratio) 1.21, partial thromboplastin time 33 s (reference = 33), fibrinogen 214 mg/dl, D-dimer 970 μg/ml, factor II 98%, and that antinuclear antibody, antiphospholipid antibodies, mutation for factor II gene (G20210A), and mutation for Arg506 Gln of factor V were all negative (factor V Leiden). There was no evidence of clinical disseminated intravascular coagulation (DIC). He was treated with low molecular weight heparin and did well. He continues to be in complete remission 7 years later with normal protein C levels. Acquired protein C deficiency can occur in a variety of settings and has been reported in acute myelocytic leukemia. However, clinically significant thrombosis in the absence of clinical DIC, such as our case, remains extremely rare.

  12. 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...

  13. DEFICIENT PROTEIN C AND PROTEIN S INDUCED ACUTE VENOUS MESENTERIC ISCHEMIA: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Darwin Britto

    2016-05-01

    Full Text Available BACKGROUND A 35 year old lady presented with unresolved severe abdominal pain and vomiting. She was diagnosed to have superior mesenteric vein thrombosis with gangrenous small bowel and multiple splenic infarcts secondary to Protein C and Protein S deficiency. She underwent emergency explorative laparotomy and extensive small bowel resection and anastomosis and splenectomy. This is to stress the importance of keeping mesenteric ischemia as an important differential diagnosis in cases of acute abdomen

  14. 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.

  15. 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.

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

    Science.gov (United States)

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

    2014-05-26

    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.

  17. Inhibition of activated protein C by recombinant alpha 1-antitrypsin variants with substitution of arginine or leucine for methionine358

    NARCIS (Netherlands)

    Heeb, M.J.; Bischoff, Rainer; Courtney, M.; Griffin, J.H.

    1990-01-01

    alpha 1-Antitrypsin (alpha 1-AT) was recently identified as a major physiologic plasma inhibitor of activated protein C. The reaction with activated protein C of recombinant alpha 1-AT containing amino acid substitutions at the reactive center was studied. The substitution of Arg358 for Met, as obse

  18. 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.

  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 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...

  1. Slow light in flight imaging

    CERN Document Server

    Wilson, Kali; Gariepy, Genevieve; Henderson, Robert; Howell, John; Faccio, Daniele

    2016-01-01

    Slow-light media are of interest in the context of quantum computing and enhanced measurement of quantum effects, with particular emphasis on using slow-light with single photons. We use light-in-flight imaging with a single photon avalanche diode camera-array to image in situ pulse propagation through a slow light medium consisting of heated rubidium vapour. Light-in-flight imaging of slow light propagation enables direct visualisation of a series of physical effects including simultaneous observation of spatial pulse compression and temporal pulse dispersion. Additionally, the single-photon nature of the camera allows for observation of the group velocity of single photons with measured single-photon fractional delays greater than 1 over 1 cm of propagation.

  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. 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)

  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. Coagulation factor V mediates inhibition of tissue factor signaling by activated protein C in mice.

    Science.gov (United States)

    Liang, Hai Po H; Kerschen, Edward J; Basu, Sreemanti; Hernandez, Irene; Zogg, Mark; Jia, Shuang; Hessner, Martin J; Toso, Raffaella; Rezaie, Alireza R; Fernández, José A; Camire, Rodney M; Ruf, Wolfram; Griffin, John H; Weiler, Hartmut

    2015-11-19

    The key effector molecule of the natural protein C pathway, activated protein C (aPC), exerts pleiotropic effects on coagulation, fibrinolysis, and inflammation. Coagulation-independent cell signaling by aPC appears to be the predominant mechanism underlying its highly reproducible therapeutic efficacy in most animal models of injury and infection. In this study, using a mouse model of Staphylococcus aureus sepsis, we demonstrate marked disease stage-specific effects of the anticoagulant and cell signaling functions of aPC. aPC resistance of factor (f)V due to the R506Q Leiden mutation protected against detrimental anticoagulant effects of aPC therapy but also abrogated the anti-inflammatory and mortality-reducing effects of the signaling-selective 5A-aPC variant that has minimal anticoagulant function. We found that procofactor V (cleaved by aPC at R506) and protein S were necessary cofactors for the aPC-mediated inhibition of inflammatory tissue-factor signaling. The anti-inflammatory cofactor function of fV involved the same structural features that govern its cofactor function for the anticoagulant effects of aPC, yet its anti-inflammatory activities did not involve proteolysis of activated coagulation factors Va and VIIIa. These findings reveal a novel biological function and mechanism of the protein C pathway in which protein S and the aPC-cleaved form of fV are cofactors for anti-inflammatory cell signaling by aPC in the context of endotoxemia and infection.

  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. 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

  8. 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

  9. 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.

  10. Natural history of five children with surfactant protein C mutations and interstitial lung disease.

    Science.gov (United States)

    Avital, Avraham; Hevroni, Avigdor; Godfrey, Simon; Cohen, Shlomo; Maayan, Channa; Nusair, Samir; Nogee, Lawrence M; Springer, Chaim

    2014-11-01

    Interstitial lung diseases in infants and children are uncommon and may be caused by specific inborn errors of surfactant metabolism. Five children with open lung biopsy diagnosed interstitial lung disease were followed (mean of 27.2 years) and evaluated for surfactant protein gene mutations. Four of the children were originally diagnosed as desquamative interstitial pneumonitis and one as chronic interstitial pneumonitis. All had good response to chloroquine or hydroxychloroquine treatment for periods of 7-38 months. Lung function tests, incremental exercise tests, and rentgenological studies were performed in the children. Surfactant protein gene mutations were searched in all the patients and in part of their families. Three of the patients, aged now 32, 29, and 37 years, feel well and have normal lung function, while two of the patients, both females, aged 28 and 37 years, conduct normal activities of daily living, have healthy children but have clinical, physiological and rentgenological evidence of restrictive lung disease. All five patients were found to have surfactant protein C gene (SFTPC) mutations, three of them with the most common mutation (p.I73T) and the other two with new mutations of surfactant protein C gene (p.I38F and p.V39L). We conclude that detection of surfactant protein mutations should be attempted in all children presenting with interstitial lung disease. Furthermore, treatment with hydroxychloroquine should be considered in children with SFTPC mutations. Prospective evaluation of hydroxychloroquine therapy in a greater number of patients is needed.

  11. 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

  12. Low Circulating Protein C Levels Are Associated with Lower Leg Ulcers in Patients with Diabetes

    Directory of Open Access Journals (Sweden)

    K. Whitmont

    2013-01-01

    Full Text Available Activated protein C (APC promotes angiogenesis and reepithelialisation and accelerates healing of diabetic ulcers. The aim of this study was to determine the relationship between the incidence of lower leg ulcers and plasma levels of APC's precursor, protein C (PC, in diabetic patients. Patients with diabetes who had a lower leg ulcer(s for >6 months (n=36 were compared with age-, type of diabetes-, and sex-matched subjects with diabetes but without an ulcer (n=36, controls. Total PC was assessed using a routine PC colorimetric assay. There was a significantly (P<0.001 lower level of plasma PC in patients with ulcers (103.3 ± 22.7, mean ± SD compared with control (127.1±34.0 subjects, when corrected for age and matched for gender and type of diabetes. Ulcer type (neuropathic, ischaemic, or mixed was not a significant covariate for plasma PC levels (P=0.35. There was no correlation between PC levels and gender, type of diabetes, HbA1c, or C-reactive protein in either group. In summary, decreased circulating PC levels are associated with, and may predispose to, lower leg ulceration in patients with diabetes.

  13. Intraperitoneal administration of activated protein C prevents postsurgical adhesion band formation.

    Science.gov (United States)

    Dinarvand, Peyman; Hassanian, Seyed Mahdi; Weiler, Hartmut; Rezaie, Alireza R

    2015-02-19

    Postsurgical peritoneal adhesion bands are the most important causes of intestinal obstruction, pelvic pain, and female infertility. In this study, we used a mouse model of adhesion and compared the protective effect of activated protein C (APC) to that of the Food and Drug Administration-approved antiadhesion agent, sodium hyaluronate/carboxymethylcellulose (Seprafilm) by intraperitoneal administration of either APC or Seprafilm to experimental animals. Pathological adhesion bands were graded on day 7, and peritoneal fluid concentrations of tissue plasminogen activator (tPA), d-dimer, thrombin-antithrombin complex, and cytokines (IL-1β, IL-6, interferon-γ, tumor necrosis factor-α, transforming growth factor-β1) were evaluated. Inflammation scores were also measured based on histologic data obtained from peritoneal tissues. Relative to Seprafilm, intraperitoneal administration of human APC led to significantly higher reduction of postsurgical adhesion bands. Moreover, a markedly lower inflammation score was obtained in the adhesive tissues of the APC-treated group, which correlated with significantly reduced peritoneal concentrations of proinflammatory cytokines and an elevated tPA level. Further studies using variants of human APC with or without protease-activated receptor 1 (PAR1) signaling function and mutant mice deficient for either endothelial protein C receptor (EPCR) or PAR1 revealed that the EPCR-dependent signaling activity of APC is primarily responsible for its protective activity in this model. These results suggest APC has therapeutic potential for preventing postsurgical adhesion bands. PMID:25575539

  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. Early cirrhosis in a young female with protein C deficiency: An extremely unusual case report with review

    Directory of Open Access Journals (Sweden)

    Nalini Bansal

    2016-01-01

    Full Text Available Protein C deficiency is a well recognized risk factor for development of venous thromboembolism but has never been reported to be associated with development of liver cirrhosis .We report a case of a 26 years old female who presented with multiple thrombosis involving superior mesenteric vein ,main portal vein and multiple cerebral veins. Liver biopsy done was reported as cirrhosis possibly due to Wilson's disease. However no improvement was seen with D penicillamine and patient's condition detiorated. Further, work up of patient revealed absence of Protein C levels in the plasma. So finally the case was diagnosed as Cirrhosis liver with Protein C deficiency as the likely etiology. We conclude that Protein C deficiency should be investigated in patients with cirrhosis with thrombotic lesions of unknown etiology.

  16. Diffusion theory of slow responses

    Institute of Scientific and Technical Information of China (English)

    李景德; 陈敏; 郑凤; 周镇宏

    1997-01-01

    When an action is applied to a macroscopic substance, there is a particular sort of slow response he sides the well-known fast response. Using diffusion theory, the characteristics of slow response in dielectric, elastic, piezoelectric, and pyroelectric relaxation may he explained A time domain spectroscopy method suitable for slow and fast responses in linear and nonlinear effects is given. Every relaxation mechanism contributes a peak in differential spectroscopy, and its position, height, and line shape show the dynamical properties of the mechanism The method of frequency domain spectroscopy is suitable only for linear fast response. Time domain spectroscopy is another nonequiv-alent powerful method. The theory is confirmed by a lot of experimental data

  17. Stochastic dynamics on slow manifolds

    Science.gov (United States)

    Constable, George W. A.; McKane, Alan J.; Rogers, Tim

    2013-07-01

    The theory of slow manifolds is an important tool in the study of deterministic dynamical systems, giving a practical method by which to reduce the number of relevant degrees of freedom in a model, thereby often resulting in a considerable simplification. In this paper we demonstrate how the same basic methodology may also be applied to stochastic dynamical systems, by examining the behaviour of trajectories conditioned on the event that they do not depart the slow manifold. We apply the method to two models: one from ecology and one from epidemiology, achieving a reduction in model dimension and illustrating the high quality of the analytical approximations.

  18. Molecular characterization of the porcine surfactant, pulmonary-associated protein C gene

    DEFF Research Database (Denmark)

    Cirera, S.; Nygård, A.B.; Jensen, H.E.;

    2006-01-01

    The surfactant, pulmonary-associated protein C (SFTPC) is a peptide secreted by the alveolar type II pneumocytes of the lung. We have characterized the porcine SFTPC gene at genomic, transcriptional, and protein levels. The porcine SFTPC is a single-copy gene on pig chromosome 14. Two transcripts...... were found in a newborn pig lung cDNA library: a full-length clone and a clone missing exon 5. cDNA sequence comparison revealed four synonymous and two nonsynonymous substitutions and in-frame insertions at the beginning of exon 5. Comparison of the SFTPC coding region between several mammals showed......-regulated in necrotic lungs of pigs infected with Actinobacillus pleuropneumoniae. Additionally, the protein levels were also decreased or absent in the necrotic tissue....

  19. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Human activated protein C variants in a rat model of arterial thrombosis

    Directory of Open Access Journals (Sweden)

    Dahlbäck Björn

    2008-10-01

    Full Text Available Abstract Background Activated protein C (APC inhibits coagulation by degrading activated factor V (FVa and factor VIII (FVIIIa, protein S (PS functioning as a cofactor to APC. Methods By mutagenesis of the vitamin K-dependent Gla domain of APC, we have recently created an APC variant having enhanced anticoagulant activity due to increased affinity for negatively charged phospholipid membranes. In the present study, the potential antithrombotic effects of this APC variant, and of a variant APC that is additionally mutated in the serine protease domain, have been evaluated in a blind randomized study in a rat model of arterial thrombosis. In this model, we have previously found the combination of bovine APC and PS to be highly antithrombotic. Four treatment groups each containing 10 rats were, in a blind random fashion, given intravenous bolus injections of wild-type or mutant variants of APC (0.8 mg/kg together with human PS (0.6 mg/kg or human PS (0.6 mg/kg alone. A control group with 20 animals where given vehicle only. Results A trend to increased patency rates was noted in a group receiving one of the APC variants, but it did not reach statistical significance. Conclusion In conclusion, administration of human APC variants having enhanced anticoagulant efficacy together with human PS in a rat model of arterial thrombosis did not give an efficient antithrombotic effect. The lack of effect may be due to species-specific differences between the human protein C system and the rat hemostatic system.

  2. Synthesis of an endothelial cell mimicking surface containing thrombomodulin and endothelial protein C receptor

    Science.gov (United States)

    Kador, Karl Erich

    Synthetic materials for use in blood contacting applications have been studied for many years with limited success. One of the main areas of need for these materials is the design of synthetic vascular grafts for use in the hundreds of thousands of patients who have coronary artery bypass grafting, many without suitable veins for autologous grafts. The design of these grafts is constrained by two common modes of failure, the formation of intimal hyperplasia (IH) and thrombosis. IH formation has been previously linked to a mismatching of the mechanical properties of the graft and has been overcome by creating grafts using materials whose compliance mimics that of the native artery. Several techniques and surface modification have been designed to limit thrombosis on the surface of synthetic materials. One which has shown the greatest promise is the immobilization of Thrombomodulin (TM), a protein found on the endothelial cell membrane lining native blood vessels involved in the activation of the anticoagulant Protein C (PC). While TM immobilization has been shown to arrest thrombin formation and limit fibrous formations in in-vitro and in-vivo experiments, it has shown to be transport limiting under arterial flow. On the endothelial cell surface, TM is co-localized with Endothelial Protein C Receptor (EPCR), which increases PC transport onto the cell surface and increases PC activation via TM between 20-100 fold. This dissertation will describe the chemical modification of medical grade polyurethane (PU), whose compliance has been shown to match that of native arteries. This modification will enable the immobilization of two proteins on an enzymatically relevant scale estimated at less than 10 nm. This dissertation will further describe the immobilization of the proteins TM and EPCR, and analyze the ability of a surface co-immobilized with these proteins to activate the anticoagulant PC. Finally, it will compare the ability of this co-immobilized surface to delay

  3. Periodic solutions and slow manifolds

    NARCIS (Netherlands)

    Verhulst, F.

    2006-01-01

    After reviewing a number of results from geometric singular perturbation theory, we give an example of a theorem for periodic solutions in a slow manifold. This is illustrated by examples involving the van der Pol-equation and a modified logistic equation. Regarding nonhyperbolic transitions we disc

  4. 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

  5. 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

  6. 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.

  7. 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".

  8. Cold and Slow Molecular Beam

    CERN Document Server

    Lu, Hsin-I; Wright, Matthew J; Patterson, Dave; 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. One modestly boosted beam has a forward velocity of vf = 65 m/s, a narrow velocity spread, and a flux of 10^9 molecules per pulse. The other has the slowest forward velocity of vf = 40 m/s, a longitudinal temperature of 3.6 K, and a flux of 5x10^8 molecules per pulse.

  9. Research Development and Perspective on Slow Slip, Tremors, and Slow Earthquakes

    Institute of Scientific and Technical Information of China (English)

    Wang Yanzhao; Shen Zhengkang

    2007-01-01

    Seismological and geodetic observations indicate that slow slip sometimes occurs in active fault zones beneath the seismogenic depth, and large slow slip can result in transient ground motion.Slow earthquakes, on the other hand, emit tremor-like signals within a narrow frequency band, and usually produce no catastrophic consequences. In general, slow slip and slow earthquakes probably correspond to deformation processes associated with releasing elastic energy in fault zones, and understanding their mechanisms may help improve our understanding of fault zone dynamic processes. This article reviews the research progress on slow slip and slow earthquakes over the last decade. Crustal motion and tremor activities associated with slow slip and slow earthquakes have been investigated extensively, mainly involving locating sources of slow slip and slow earthquakes and numerical modeling of their processes. In the meantime, debates have continued about slow slip and slow earthquakes,such as their origins, relationship, and mechanisms.

  10. 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...

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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...

  1. Low affinity and slow Na+-binding precedes high affinity aspartate binding in GltPh

    NARCIS (Netherlands)

    Hänelt, Inga; Jensen, Sonja; Wunnicke, Dorith; Slotboom, Dirk Jan

    2015-01-01

    GltPh from Pyrococcus horikoshii is a homotrimeric Na+-coupled aspartate transporter. It belongs to the widespread family of glutamate transporters, which also includes the mammalian excitatory amino acid transporters (EAATs) that take up the neurotransmitter glutamate. Each protomer in GltPh consis

  2. 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....

  3. Endogenous activated protein C limits cancer cell extravasation through sphingosine-1-phosphate receptor 1-mediated vascular endothelial barrier enhancement

    NARCIS (Netherlands)

    G.L. van Sluis; T.M.H. Niers; C.T. Esmon; W. Tigchelaar; D.J. Richel; H.R. Buller; C.J.F. van Noorden; C.A. Spek

    2009-01-01

    Activated protein C (APC) has both anticoagulant activity and direct cell-signaling properties. APC has been reported to promote cancer cell migration/invasion and to inhibit apoptosis and therefore may exacerbate metastasis. Opposing these activities, APC signaling protects the vascular endothelial

  4. Budd-Chiari syndrome during nephrotic relapse in a patient with resistance to activated protein C clotting inhibitor.

    Science.gov (United States)

    Gambaro, G; Patrassi, G; Pittarello, F; Nardellotto, A; Checchetto, S; D'Angelo, A

    1998-10-01

    It has long been known that patients with nephrotic syndrome have a hypercoagulable state, which explains the association between nephrotic syndrome, renal vein thrombosis, and thromboembolism. However, the Budd-Chiari syndrome has never been reported in nephrotic patients. This is the first report of such an association that, most likely, depended on a primary resistance to activated protein C.

  5. Integrated Photonics Enabled by Slow Light

    DEFF Research Database (Denmark)

    Mørk, Jesper; Chen, Yuntian; Ek, Sara;

    2012-01-01

    In this talk we will discuss the physics of slow light in semiconductor materials and in particular the possibilities offered for integrated photonics. This includes ultra-compact slow light enabled optical amplifiers, lasers and pulse sources.......In this talk we will discuss the physics of slow light in semiconductor materials and in particular the possibilities offered for integrated photonics. This includes ultra-compact slow light enabled optical amplifiers, lasers and pulse sources....

  6. Slowing Down in Chemical Tristability Systems

    Institute of Scientific and Technical Information of China (English)

    ZHAN,Ye-Hong(詹业宏); ZHANG,Chun-Hua(张春华); WU,Fu-Gen(吴福根); HU,Yi-Hua(胡义华)

    2001-01-01

    In this paper two kinds of slowing down in the chamical tristability systems are studied. One is the critical slowing down at the edges of tristable reion, and the other is the slowing down far from the critical point, which has much to do with the unstable steady-points. The results possess some universal propererties.

  7. 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.

  8. Protein C-terminal labeling and biotinylation using synthetic peptide and split-intein.

    Directory of Open Access Journals (Sweden)

    Gerrit Volkmann

    Full Text Available BACKGROUND: Site-specific protein labeling or modification can facilitate the characterization of proteins with respect to their structure, folding, and interaction with other proteins. However, current methods of site-specific protein labeling are few and with limitations, therefore new methods are needed to satisfy the increasing need and sophistications of protein labeling. METHODOLOGY: A method of protein C-terminal labeling was developed using a non-canonical split-intein, through an intein-catalyzed trans-splicing reaction between a protein and a small synthetic peptide carrying the desired labeling groups. As demonstrations of this method, three different proteins were efficiently labeled at their C-termini with two different labels (fluorescein and biotin either in solution or on a solid surface, and a transferrin receptor protein was labeled on the membrane surface of live mammalian cells. Protein biotinylation and immobilization on a streptavidin-coated surface were also achieved in a cell lysate without prior purification of the target protein. CONCLUSIONS: We have produced a method of site-specific labeling or modification at the C-termini of recombinant proteins. This method compares favorably with previous protein labeling methods and has several unique advantages. It is expected to have many potential applications in protein engineering and research, which include fluorescent labeling for monitoring protein folding, location, and trafficking in cells, and biotinylation for protein immobilization on streptavidin-coated surfaces including protein microchips. The types of chemical labeling may be limited only by the ability of chemical synthesis to produce the small C-intein peptide containing the desired chemical groups.

  9. 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.

  10. 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

  11. 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

  12. 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.

  13. Single amino acid substitutions dissociate fibrinogen-clotting and thrombomodulin-binding activities of human thrombin.

    OpenAIRE

    Wu, Q Y; Sheehan, J P; Tsiang, M; Lentz, S R; Birktoft, J J; Sadler, J E

    1991-01-01

    Thrombin is a serine protease that acts as a procoagulant by clotting fibrinogen and activating platelets and as an anticoagulant by activating protein C in a thrombomodulin-dependent reaction. Fibrinogen and thrombomodulin bind competitively to an anion-binding exosite on thrombin. We prepared recombinant normal human thrombin and mutant thrombins with single amino acid substitutions in order to localize and distinguish the fibrinogen- and thrombomodulin-binding sites. Normal and mutant thro...

  14. 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.

  15. 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.

  16. 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)

  17. 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.

  18. 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 ...

  19. Determination of coagulation inhibitor levels and resistance to activated protein C in patients undergoing gastric surgery for benign and malignant disorders

    DEFF Research Database (Denmark)

    Andersen, B S; Rahr, H B; Sørensen, J V

    1997-01-01

    The aim of the present study was to determine plasma levels of protein C antigen (PC:Ag) and activity (PC:Act), tissue factor pathway inhibitor (TFPI), protein S (PS), antithrombin (AT), heparin cofactor II (HCII), and resistance to activated protein C (APCR) before, during and after elective...

  20. 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

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

    DEFF Research Database (Denmark)

    Boon, Arnold; Oh, V M; Taylor, John E.;

    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-...

  2. 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...

  3. 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

  4. 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.

  5. 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....

  6. Tandem queue with server slow-down

    NARCIS (Netherlands)

    D.I. Miretskiy; W.R.W. Scheinhardt; M.R.H. Mandjes

    2007-01-01

    We study how rare events happen in the standard two-node tandem Jackson queue and in a generalization, the socalled slow-down network, see [2]. In the latter model the service rate of the first server depends on the number of jobs in the second queue: the first server slows down if the amount of job

  7. 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…

  8. Slow Movements of Bio-Inspired Limbs

    Science.gov (United States)

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

    2016-10-01

    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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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 ...

  14. Deficiencies of proteins C, S and Antithrombin and factor V Leiden and the risk of ischemic strokes

    Science.gov (United States)

    Popa, C

    2010-01-01

    Although hypercoagulable states are most often associated with venous thromboses, arterial thromboses are reported in protein C, protein S, antithrombin deficient patients and in those with factor V Leiden, components of hereditary thrombophilia. Because these arterial thromboses (peripheral artery disease, myocardial infarction, and cerebral infarction) mostly affect young persons, aged below 45 years, it is important to test and treat these thrombophilic defects. Because the relation thrombophilia – arterial thromboses is still under debate, due to conflicting data, this article is a review of studies published in literature regarding the implication of the above–mentioned thrombophilic defects in cerebral infarcts. PMID:20945813

  15. 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...

  16. KEK-IMSS Slow Positron Facility

    Science.gov (United States)

    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.

    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-). 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. Generation and evolution of interplanetary slow shocks

    Directory of Open Access Journals (Sweden)

    C.-C. Wu

    Full Text Available It is well known that most MHD shocks observed within 1 AU are MHD fast shocks. Only a very limited number of MHD slow shocks are observed within 1 AU. In order to understand why there are only a few MHD slow shocks observed within 1 AU, we use a one-dimensional, time-dependent MHD code with an adaptive grid to study the generation and evolution of interplanetary slow shocks (ISS in the solar wind. Results show that a negative, nearly square-wave perturbation will generate a pair of slow shocks (a forward and a reverse slow shock. In addition, the forward and the reverse slow shocks can pass through each other without destroying their characteristics, but the propagating speeds for both shocks are decreased. A positive, square-wave perturbation will generate both slow and fast shocks. When a forward slow shock (FSS propagates behind a forward fast shock (FFS, the former experiences a decreasing Mach number. In addition, the FSS always disappears within a distance of 150R (where R is one solar radius from the Sun when there is a forward fast shock (with Mach number ≥1.7 propagating in front of the FSS. In all tests that we have performed, we have not discovered that the FSS (or reverse slow shock evolves into a FFS (or reverse fast shock. Thus, we do not confirm the FSS-FFS evolution as suggested by Whang (1987.

  2. Protein C Thr315Ala variant results in gain of function but manifests as type II deficiency in diagnostic assays.

    Science.gov (United States)

    Ding, Qiulan; Yang, Likui; Dinarvand, Peyman; Wang, Xuefeng; Rezaie, Alireza R

    2015-04-01

    Protein C (PC) is a vitamin K-dependent plasma glycoprotein, which upon activation by thrombin in complex with thrombomodulin (TM), regulates the coagulation cascade through a feedback loop inhibition mechanism. PC deficiency is associated with an increased risk of venous thromboembolism (VTE). A recent cohort study aimed at establishing a normal PC range identified a healthy PC-deficient subject whose PC antigen level of 65% and activity levels of 50% (chromogenic assay) and 36% (clotting assay) were markedly low. The proband has a negative family history of VTE. Genetic analysis revealed the proband has a heterozygous missense mutation in which Thr-315 of the PC heavy chain has been substituted with Ala. We expressed this mutant in HEK-293 cells and purified it to homogeneity. A similar decrease in both anticoagulant and anti-inflammatory activities of the activated protein C mutant was observed in plasma- and cell-based assays. Interestingly, we discovered if functional assays were coupled to PC activation by the thrombin-TM complex, the variant exhibits improved activities in all assays. Sequence analysis revealed Thr-315 is a consensus N-linked glycosylation site for Asn-313 and that its elimination significantly (∼four- to fivefold) improves the maximum velocity of PC activation by the thrombin-TM complex, explaining the basis for the proband's negative VTE pedigree. PMID:25651845

  3. 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 ...

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.)

  9. 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

  10. 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...

  11. 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...

  12. 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...

  13. 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.

  14. 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.

  15. Mesenteric and splenic venous thrombosis in a female patient with essential thrombocytosis and the resistance to activated protein C

    Directory of Open Access Journals (Sweden)

    Marisavljević Dragomir

    2003-01-01

    Full Text Available Splenic venous thrombosis is a rare disease in which an underlying hypercoagulable state can often be found. A 27-years old female patient with recurrent mesenteric venous and splenic thrombosis as a severe complication of an association of resistance to activated protein C and essential thrombocythemia is presented in this report. Establishing the diagnosis of essential thrombocytosis was particularly difficult because this was the case of the so called "silent" myeloproliferative disorder. The number of thrombocytes was almost normal before the splenectomy performed because of the splenic venous thrombosis. Thus, spontaneous growth of erythroid and megakaryocyte colonies in vitro and the clinical course of the disease were the clues for establishing the diagnosis, because the number of thrombocytes reached the values over 1500×109/l after only 1.5 years of the follow-up. The case of this patient was interesting particularly from the surgical point of view because of the management strategy.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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 ...

  1. 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.

  2. 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.

  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. 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...

  5. 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.)

  6. 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.

  7. Humoral immune response to outer surface protein C of Borrelia burgdorferi in Lyme disease: role of the immunoglobulin M response in the serodiagnosis of early infection.

    Science.gov (United States)

    Fung, B P; McHugh, G L; Leong, J M; Steere, A C

    1994-08-01

    We determined the humoral immune response to outer surface protein C (OspC) of Borrelia burgdorferi in patients with early or late manifestations of Lyme disease and investigated the use of this antigen in the serodiagnosis of early infection. The ospC gene from the low-passage human isolate 297, a North American B. burgdorferi strain, was used to make a recombinant maltose-binding protein (MBP)-OspC fusion protein for serologic tests. This gene showed 84 to 85% nucleotide sequence identity and 76 to 79% amino acid identity with ospC of B. burgdorferi B31 and 2591. The antibody responses to MBP-OspC were determined in serial sera from 15 patients with Lyme disease who were monitored for 4 to 12 years of illness, in single-serum samples from 189 patients with early or late manifestations of the disorder, and in serum samples from 106 control patients. Early in the infection, patients with erythema migrans or meningitis commonly had weak to strong immunoglobulin M (IgM) responses to OspC and sometimes weak to moderate IgG responses. Months to years later, weak to strong IgG reactivity with this protein was often apparent in patients with arthritis, but this response was weak or absent in patients with chronic neuroborreliosis. When acute- and convalescent-phase serum samples from patients with erythema migrans were tested for reactivity against MBP-OspC, the sensitivity of the IgM test was 73% and the specificity was 98%, with either enzyme-linked immunosorbent assay (ELISA) or Western blotting. We conclude that the majority of patients with Lyme disease have a prominent IgM response to OspC early in the illness, which is often followed by a prominent IgG response in patients with arthritis. For the serodiagnosis of early infection, the sensitivity and specificity of IgM ELISA and Western blotting were comparable or slightly improved when MBP-OspC was used as the antigen compared with tests in which spirochetal lysates were used.

  8. The slow death of most galaxies

    CERN Document Server

    Cattaneo, Andrea

    2016-01-01

    For most galaxies, the shutdown of star formation was a slow process that took four billion years. An analysis of thousands of galaxies suggests that 'strangulation' by their environment was the most likely cause. See Letter on page 192 of Peng, Maiolino and Cochrane (2015), Nature, vol. 521.

  9. Textile slow release systems with medical applications

    NARCIS (Netherlands)

    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 conve

  10. 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...

  11. Relationship between endothelial cell protein C receptor gene 6936A/G polymorphisms and deep venous thrombosis

    Institute of Scientific and Technical Information of China (English)

    CHEN Xu-dong; TIAN Lu; LI Ming; JIN Wei; ZHANG Hong-kun; ZHENG Cheng-fei

    2011-01-01

    Background Deep venous thrombosis (DVT) can result in pulmonary embolism, a fatal complication that is due to the dislodgement and movement of a blood clot (thrombus) from a limb into the lungs. Genetic risk factors related to DVT development include mutations in coagulation proteins, especially the endothelial protein C receptor (EPCR), a component of the anticoaguiation protein C (PC) pathway. The objective of the present study was to analyze the relationship between the 6936A/G polymorphism in the EPCR gene and the occurrence of DVT.Methods This study involved 65 patients with DVT and 71 age- and gender-matched healthy controls. Peripheral blood samples were collected from all subjects. Plasma levels of soluble EPCR (sEPCR) were measured by enzyme-linked immunosorbent assay. Genomic DNA was extracted and EPCR gene product was amplified by a standard PCR reaction.Gene product bands were sequenced to identify EPCR gene polymorphisms.Results In the control group, the level of sEPCR in subjects with 6936AG genotype was significantly higher than that in subjects with 6936AA genotype ((0.97±0.32) pg/ml vs. (0.61±0.24) pg/ml, P <0.01). Similarly in the DVT group, the level of sEPCR in subjects with the 6936AG were greater than that in subjects with the 6936AA genotype ((0.87±0.21) pg/ml vs. (0.50±0.18) pg/ml, P <0.01). The sEPCR level in DVT patients was significantly higher than that in healthy controls ((0.68±0.32) pg/ml vs. (0.54±0.22) pg/ml, P <0.05). The 6936AG genotype frequency in DVT patients was significantly higher than that in healthy controls (P <0.05). In contrast, the 6936AA genotype frequency in DVT patients was lower than that in healthy controls (P <0.05). Subjects carrying 6936AG had an increased risk of thrombosis (OR=2.75, 95% CI:1.04-7.30, P <0.05).Conclusions EPCR gene 6936A/G polymorphism is associated with increased plasma levels of sEPCR. Subjects carrying 6936AG likely have an increased risk of thrombosis.

  12. 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

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

    Directory of Open Access Journals (Sweden)

    Fuguo Liu

    2016-07-01

    Full Text Available 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.

  15. Safety of plasma-derived protein C for treating disseminated intravascular coagulation in adult patients with active cancer.

    Science.gov (United States)

    Malato, Alessandra; Saccullo, Giorgia; Coco, Lucio Lo; Caracciolo, Clementina; Raso, Simona; Santoro, Marco; Zammit, Valentina; Siragusa, Sergio

    2012-02-01

    Cancer-related disseminated intravascular coagulation (DIC) is a life-threatening condition for which no effective treatment is currently available. Protein C (PC), a modulator of coagulation as well as the inflammatory system, has been successfully tested (in its activated recombinant form [a-rPC]) in sepsis-related coagulopathy, but with an increased risk for major bleeding. Plasma-derived PC (pd-PC) is more suitable than a-rPC in patients at high risk from bleeding due to its self-limiting process. We carried out a single-arm study evaluating the role of pd-PC in adult cancer patients with overt DIC. Over a period of 3 years, we treated 19 patients with overt DIC and a PC plasma concentration coagulation, haematological tests, and the DIC score were recorded after 12, 24, 48 hr, 7 and 10 days, while clinical outcomes (bleeding, thrombosis and mortality) were recorded up to 28 days. Within 48 hr of starting pd-PC therapy, laboratory tests as well as the DIC score improved in all patients. At 28-days follow-up, no bleeding or thrombosis was observed. This is the first study to investigate the use of pd- PC for treatment of cancer-related overt DIC.

  16. 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.

  17. 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

  18. 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

    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......-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...

  19. 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

  20. 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.

  1. 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...

  2. Analyzing binding data.

    Science.gov (United States)

    Motulsky, Harvey J; Neubig, Richard R

    2010-07-01

    Measuring the rate and extent of radioligand binding provides information on the number of binding sites, and their affinity and accessibility of these binding sites for various drugs. This unit explains how to design and analyze such experiments.

  3. 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...

  4. 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)

  5. Recurrent slow slip event reveals the interaction with seismic slow earthquakes and disruption from large earthquake

    Science.gov (United States)

    Liu, Zhen; Moore, Angelyn W.; Owen, Susan

    2015-09-01

    It remains enigmatic how slow slip events (SSEs) interact with other slow seismic events and large distant earthquakes at many subduction zones. Here we model the spatiotemporal slip evolution of the most recent long-term SSE in 2009-2011 in the Bungo Channel region, southwest Japan using GEONET GPS position time-series and a Kalman filter-based, time-dependent slip inversion method. We examine the space-time relationship between the geodetically determined slow slip transient and seismically observed low frequency earthquakes (LFEs) and very-low frequency earthquakes (V-LFEs) near the Nankai trough. We find a strong but distinct temporal correlation between transient slip and LFEs and V-LFEs, suggesting a different relationship to the SSE. We also find the great Tohoku-Oki earthquake appears to disrupt the normal source process of the SSE, probably reflecting large-scale stress redistribution caused by the earthquake. Comparison of the 2009-2011 SSE with others in the same region shows much similarity in slip and moment release, confirming its recurrent nature. Comparison of transient slip with plate coupling shows that slip transients mainly concentrate on the transition zone from strong coupling region to downdip LFEs with transient slip relieving elastic strain accumulation at transitional depth. The less consistent spatial correlation between the long-term SSE and seismic slow earthquakes, and susceptibility of these slow earthquakes to various triggering sources including long-term slow slip, suggests caution in using the seismically determined slow earthquakes as a proxy for slow slip.

  6. 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 ...

  7. 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.

  8. 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...

  9. Motor slowing in asymptomatic HIV infection.

    Science.gov (United States)

    Fitzgibbon, M L; Cella, D F; Humfleet, G; Griffin, E; Sheridan, K

    1989-06-01

    To examine neuropsychological deficits associated with the human immunodeficiency virus (HIV), 25 asymptomatic homosexual men and sexual partners of intravenous drug users and 25 seronegative homosexual men and nonhigh-risk heterosexuals were assessed on measures of fine motor control, visual scanning, attention, depression, and global psychological functioning. Analysis suggested that HIV infection is associated with reduced fine motor control. Seropositivity is associated with elevated depression and global psychological maladjustment. When depression and global adjustment were analyzed as covariates, motor slowing was evident in the seropositive group. These findings suggest an association between motor slowing and HIV infection in asymptomatic subjects and point to the necessity of measuring affect at least as a control variable. Further study is needed to determine whether the fine motor deficit evident in this sample is limited to distinct subgrouping of the over-all sample. PMID:2762096

  10. 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.

  11. Quake clamps down on slow slip

    Science.gov (United States)

    Wallace, Laura M.; Bartlow, Noel; Hamling, Ian; Fry, Bill

    2014-12-01

    Using continuous GPS (cGPS) data from the Hikurangi subduction zone in New Zealand, we show for the first time that stress changes induced by a local earthquake can arrest an ongoing slow slip event (SSE). The cGPS data show that the slip rate in the northern portion of the 2013/2014 Kapiti SSE decreased abruptly following a nearby intraslab earthquake. We suggest that deceleration of the Kapiti SSE in early 2014 occurred due to a tenfold increase in the normal stress relative to shear stress in the SSE source, induced by the nearby Mw 6.3 earthquake, consistent with expectations of rate and state friction. Our observation of an abrupt halting/slowing of the SSE in response to stress changes imposed by a local earthquake has implications for the strength of fault zones hosting SSEs and supports the premise that static stress changes are an important ingredient in triggering (or delaying) fault slip.

  12. 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

  13. 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.

  14. Polymeric membrane studied using slow positron beam

    Energy Technology Data Exchange (ETDEWEB)

    Hung, W.-S.; Lo, C.-H. [R and D Center for Membrane Technology, Chung Yuan Christian University, Chung-Li 32023, Taiwan (China); Department of Chemical Engineering, Chung Yuan Christian University, Chung-Li 32023, Taiwan (China); Cheng, M.-L. [Department of Chemistry, University of Missouri-Kansas City, Kansas City, MO 64110 (United States); Department of Chemical Engineering and Materials Science, Yuan Ze University, Chung-Li 32003, Taiwan (China); Chen Hongmin; Liu Guang; Chakka, Lakshmi [Department of Chemistry, University of Missouri-Kansas City, Kansas City, MO 64110 (United States); Nanda, D.; Tung, K.-L.; Huang, S.-H.; Lee, Kueir-Rarn; Lai, J.-Y. [R and D Center for Membrane Technology, Chung Yuan Christian University, Chung-Li 32023, Taiwan (China); Department of Chemical Engineering, Chung Yuan Christian University, Chung-Li 32023, Taiwan (China); Sun Yiming [R and D Center for Membrane Technology, Chung Yuan Christian University, Chung-Li 32023, Taiwan (China); Department of Chemical Engineering and Materials Science, Yuan Ze University, Chung-Li 32003, Taiwan (China); Yu Changcheng [R and D Center for Membrane Technology, Chung Yuan Christian University, Chung-Li 32023, Taiwan (China); Department of Physics, Chung Yuan Christian University, Chung-Li 32023, Taiwan (China); Zhang Renwu [Physical Science Department, Southern Utah University, Cedar City, UT 84720 (United States); Jean, Y.C. [R and D Center for Membrane Technology, Chung Yuan Christian University, Chung-Li 32023, Taiwan (China); Department of Chemical Engineering, Chung Yuan Christian University, Chung-Li 32023, Taiwan (China); Department of Chemistry, University of Missouri-Kansas City, Kansas City, MO 64110 (United States)], E-mail: jeany@umkc.edu

    2008-10-31

    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.

  15. 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.

  16. 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...

  17. 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...

  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. Brane inflation without slow-roll

    CERN Document Server

    Matsuda, T

    2007-01-01

    The scenario of brane inflation without using the conventional slow-roll approximations has been investigated. Based on the mechanism of generating the curvature perturbations at the end of inflation, a new brane inflation paradigm was developed. The conditions for making a sufficiently large enough number of e-foldings and for generating the curvature perturbations without producing dangerous relics were also examined. Benefits of our scenario are subsequently discussed in detail.

  1. Brane inflation without slow-roll

    Science.gov (United States)

    Matsuda, Tomohiro

    2007-03-01

    The scenario of brane inflation without using the conventional slow-roll approximations has been investigated. Based on the mechanism of generating the curvature perturbations at the end of inflation, a new brane inflation paradigm was developed. The conditions for making a sufficiently large enough number of e-foldings and for generating the curvature perturbations without producing dangerous relics were also examined. Benefits of our scenario are subsequently discussed in detail.

  2. 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

  3. Method for monitoring slow dynamics recovery

    Science.gov (United States)

    Haller, Kristian C. E.; Hedberg, Claes M.

    2012-11-01

    Slow Dynamics is a specific material property, which for example is connected to the degree of damage. It is therefore of importance to be able to attain proper measurements of it. Usually it has been monitored by acoustic resonance methods which have very high sensitivity as such. However, because the acoustic wave is acting both as conditioner and as probe, the measurement is affecting the result which leads to a mixing of the fast nonlinear response to the excitation and the slow dynamics material recovery. In this article a method is introduced which, for the first time, removes the fast dynamics from the process and allows the behavior of the slow dynamics to be monitored by itself. The new method has the ability to measure at the shortest possible recovery times, and at very small conditioning strains. For the lowest strains the sound speed increases with strain, while at higher strains a linear decreasing dependence is observed. This is the first method and test that has been able to monitor the true material state recovery process.

  4. 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 unexpec...

  5. A thrombomodulin mutation that impairs active protein C generation is detrimental in severe pneumonia-derived gram-negative sepsis (melioidosis.

    Directory of Open Access Journals (Sweden)

    Liesbeth M Kager

    2014-04-01

    Full Text Available BACKGROUND: During severe (pneumosepsis inflammatory and coagulation pathways become activated as part of the host immune response. Thrombomodulin (TM is involved in a range of host defense mechanisms during infection and plays a pivotal role in activation of protein C (PC into active protein C (APC. APC has both anticoagulant and anti-inflammatory properties. In this study we investigated the effects of impaired TM-mediated APC generation during melioidosis, a common form of community-acquired Gram-negative (pneumosepsis in South-East Asia caused by Burkholderia (B. pseudomallei. METHODOLOGY/PRINCIPAL FINDINGS: (WT mice and mice with an impaired capacity to activate protein C due to a point mutation in their Thbd gene (TMpro/pro mice were intranasally infected with B. pseudomallei and sacrificed after 24, 48 or 72 hours for analyses. Additionally, survival studies were performed. When compared to WT mice, TMpro/pro mice displayed a worse survival upon infection with B. pseudomallei, accompanied by increased coagulation activation, enhanced lung neutrophil influx and bronchoalveolar inflammation at late time points, together with increased hepatocellular injury. The TMpro/pro mutation had limited if any impact on bacterial growth and dissemination. CONCLUSION/SIGNIFICANCE: TM-mediated protein C activation contributes to protective immunity after infection with B. pseudomallei. These results add to a better understanding of the regulation of the inflammatory and procoagulant response during severe Gram-negative (pneumosepsis.

  6. 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

  7. Nonlinear dynamical triggering of slow slip

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Paul A [Los Alamos National Laboratory; Knuth, Matthew W [WISCONSIN; Kaproth, Bryan M [PENN STATE; Carpenter, Brett [PENN STATE; Guyer, Robert A [Los Alamos National Laboratory; Le Bas, Pierre - Yves [Los Alamos National Laboratory; Daub, Eric G [Los Alamos National Laboratory; Marone, Chris [PENN STATE

    2010-12-10

    Among the most fascinating, recent discoveries in seismology have been the phenomena of triggered slip, including triggered earthquakes and triggered-tremor, as well as triggered slow, silent-slip during which no seismic energy is radiated. Because fault nucleation depths cannot be probed directly, the physical regimes in which these phenomena occur are poorly understood. Thus determining physical properties that control diverse types of triggered fault sliding and what frictional constitutive laws govern triggered faulting variability is challenging. We are characterizing the physical controls of triggered faulting with the goal of developing constitutive relations by conducting laboratory and numerical modeling experiments in sheared granular media at varying load conditions. In order to simulate granular fault zone gouge in the laboratory, glass beads are sheared in a double-direct configuration under constant normal stress, while subject to transient perturbation by acoustic waves. We find that triggered, slow, silent-slip occurs at very small confining loads ({approx}1-3 MPa) that are smaller than those where dynamic earthquake triggering takes place (4-7 MPa), and that triggered slow-slip is associated with bursts of LFE-like acoustic emission. Experimental evidence suggests that the nonlinear dynamical response of the gouge material induced by dynamic waves may be responsible for the triggered slip behavior: the slip-duration, stress-drop and along-strike slip displacement are proportional to the triggering wave amplitude. Further, we observe a shear-modulus decrease corresponding to dynamic-wave triggering relative to the shear modulus of stick-slips. Modulus decrease in response to dynamical wave amplitudes of roughly a microstrain and above is a hallmark of elastic nonlinear behavior. We believe that the dynamical waves increase the material non-affine elastic deformation during shearing, simultaneously leading to instability and slow-slip. The inferred

  8. TNF Regulates Essential Alternative Complement Pathway Components and Impairs Activation of Protein C in Human Glomerular Endothelial Cells.

    Science.gov (United States)

    Sartain, Sarah E; Turner, Nancy A; Moake, Joel L

    2016-01-15

    Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy with severe renal injury secondary to an overactive alternative complement pathway (AP). aHUS episodes are often initiated or recur during inflammation. We investigated gene expression of the surface complement regulatory proteins (CD55, CD59, CD46, and CD141 [thrombomodulin]) and AP components in human glomerular microvascular endothelial cells (GMVECs) and in HUVECs, a frequently used investigational model of endothelial cells. Surface complement regulatory proteins were also quantified by flow cytometry. All experiments were done with and without exposure to IL-1β or TNF. Without cytokine stimulation, we found that GMVECs had greater AP activation than did HUVECs. With TNF stimulation, THBD gene expression and corresponding CD141 surface presence in HUVECs and GMVECs were reduced, and gene expression of complement components C3 (C3) and factor B (CFB) was increased. Consequently, AP activation, measured by Ba production, was increased, and conversion of protein C (PC) to activated PC by CD141-bound thrombin was decreased, in GMVECs and HUVECs exposed to TNF. IL-1β had similar, albeit lesser, effects on HUVEC gene expression, and it only slightly affected GMVEC gene expression. To our knowledge, this is the first detailed study of the expression/display of AP components and surface regulatory proteins in GMVECs with and without cytokine stimulation. In aHUS patients with an underlying overactive AP, additional stimulation of the AP and inhibition of activated PC-mediated anticoagulation in GMVECs by the inflammatory cytokine TNF are likely to provoke episodes of renal failure. PMID:26673143

  9. Role of pathogenicity determinant protein C (PdpC in determining the virulence of the Francisella tularensis subspecies tularensis SCHU.

    Directory of Open Access Journals (Sweden)

    Akihiko Uda

    Full Text Available Francisella tularensis subspecies tularensis, the etiological agent of tularemia, is highly pathogenic to humans and animals. However, the SCHU strain of F. tularensis SCHU P0 maintained by passaging in artificial media has been found to be attenuated. To better understand the molecular mechanisms behind the pathogenicity of F. tularensis SCHU, we attempted to isolate virulent bacteria by serial passages in mice. SCHU P5 obtained after 5th passages in mice remained avirulent, while SCHU P9 obtained after 9th passages was completely virulent in mice. Moreover, SCHU P9 grew more efficiently in J774.1 murine macrophages compared with that in the less pathogenic SCHU P0 and P5. Comparison of the nucleotide sequences of the whole genomes of SCHU P0, P5, and P9 revealed only 1 nucleotide difference among P0, P5 and P9 in 1 of the 2 copies of pathogenicity determinant protein C (pdpC gene. An adenine residue deletion was observed in the pdpC1 gene of SCHU P0, P5, and P9 and in the pdpC2 gene of SCHU P0, and P5, while P9 was characterized by the wild type pdpC2 gene. Thus, SCHU P0 and P5 expressed only truncated forms of PdpC protein, while SCHU P9 expressed both wild type and truncated versions. To validate the pathogenicity of PdpC, both copies of the pdpC gene in SCHU P9 have been inactivated by Targetron mutagenesis. SCHU P9 mutants with inactivated pdpC gene showed low intracellular growth in J774.1 cells and did not induce severe disease in experimentally infected mice, while virulence of the mutants was restored by complementation with expression of the intact PdpC. These results demonstrate that PdpC is crucial in determining the virulence of F. tularensis SCHU.

  10. Circulating microparticles, protein C, free protein S and endothelial vascular markers in children with sickle cell anaemia

    Directory of Open Access Journals (Sweden)

    Andrea Piccin

    2015-11-01

    Full Text Available Introduction: Circulating microparticles (MP have been described in sickle cell anaemia (SCA; however, their interaction with endothelial markers remains unclear. We investigated the relationship between MP, protein C (PC, free protein S (PS, nitric oxide (NO, endothelin-1 (ET-1 and adrenomedullin (ADM in a large cohort of paediatric patients. Method: A total of 111 children of African ethnicity with SCA: 51 in steady state; 15 in crises; 30 on hydroxyurea (HU therapy; 15 on transfusion; 17 controls (HbAA of similar age/ethnicity. MP were analysed by flow cytometry using: Annexin V (AV, CD61, CD42a, CD62P, CD235a, CD14, CD142 (tissue factor, CD201 (endothelial PC receptor, CD62E, CD36 (TSP-1, CD47 (TSP-1 receptor, CD31 (PECAM, CD144 (VE-cadherin. Protein C, free PS, NO, pro-ADM and C-terminal ET-1 were also measured. Results: Total MP AV was lower in crisis (1.26×106 ml−1; 0.56–2.44×106 and steady state (1.35×106 ml−1; 0.71–3.0×106 compared to transfusion (4.33×106 ml−1; 1.6–9.2×106, p0.9, p<0.05 between total numbers of AV-positive MP (MP AV and platelet MP expressing non-activation platelet markers. There was a lower correlation between MP AV and MP CD62P (R=0.73, p<0.05 (platelet activation marker, and also a lower correlation between percentage of MP expressing CD201 (%MP CD201 and %MP CD14 (R=0.627, p<0.001. %MP CD201 was higher in crisis (11.6% compared with HbAA (3.2%, p<0.05; %MP CD144 was higher in crisis (7.6% compared with transfusion (2.1%, p<0.05; %CD14 (0.77% was higher in crisis compared with transfusion (0.0%, p<0.05 and steady state (0.0%, p<0.01; MP CD14 was detectable in a higher number of samples (92% in crisis compared with the rest (40%; %MP CD235a was higher in crisis (17.9% compared with transfusion (8.9%, HU (8.7% and steady state (9.9%, p<0.05; %CD62E did not differ significantly across the groups and CD142 was undetectable. Pro-ADM levels were raised in chest crisis: 0.38 nmol L−1 (0.31–0

  11. 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

  12. 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.

  13. 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.

  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. 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...

  16. 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...

  17. 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.

  18. 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...

  19. 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...

  20. 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)

  1. Slow slip event at Kilauea Volcano

    Science.gov (United States)

    Poland, Michael P.; Miklius, Asta; Wilson, J. David; Okubo, Paul G.; Montgomery-Brown, Emily; Segall, Paul; Brooks, Benjamin; Foster, James; Wolfe, Cecily; Syracuse, Ellen; Thurbe, Clifford

    2010-01-01

    Early in the morning of 1 February 2010 (UTC; early afternoon 31 January 2010 local time), continuous Global Positioning System (GPS) and tilt instruments detected a slow slip event (SSE) on the south flank of Kilauea volcano, Hawaii. The SSE lasted at least 36 hours and resulted in a maximum of about 3 centimeters of seaward displacement. About 10 hours after the start of the slip, a flurry of small earthquakes began (Figure 1) in an area of the south flank recognized as having been seismically active during past SSEs [Wolfe et al., 2007], suggesting that the February earthquakes were triggered by stress associated with slip [Segall et al., 2006].

  2. Improvement of pedestrian flow by slow rhythm

    Science.gov (United States)

    Yanagisawa, Daichi; Tomoeda, Akiyasu; Nishinari, Katsuhiro

    2012-01-01

    We have developed a simple model for pedestrians by dividing walking velocity into two parts, which are step size and pace of walking (number of steps per unit time). Theoretical analysis on pace indicates that rhythm that is slower than normal-walking pace in a low-density regime increases flow if the flow-density diagram is convex downward in a high-density regime. In order to verify this result, we have performed an experiment with real pedestrians and observed the improvement of flow in a congested situation using slow rhythm.

  3. 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

  4. 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.

  5. 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...

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

    DEFF Research Database (Denmark)

    Søndergaard, Thomas; Beermann, J.; 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...

  7. 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

  8. 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.

  9. 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...

  10. 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...

  11. 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....

  12. 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....

  13. 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…

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. Slow-Binding Inhibition: A Theoretical and Practical Course for Students

    Science.gov (United States)

    Golicnik, Marko; Stojan, Jure

    2004-01-01

    Tyrosinase (EC 1.14.18.1) catalyzes the oxidation of L-3,4-dihydroxyphenylalanine (L-DOPA) to 2,3,5,6-tetrahydro-5,6-dioxo-1H-indole-2-carboxylate (dopachrome), according to the classical Michaelis-Menten kinetic mechanism. The enzyme is strongly but slowly inhibited by alpha-amino-beta-[N-(3-hydroxy-4-pyridone)] propionic acid (L-mimosine), a…

  19. 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.

  20. 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.

  1. What is the evidence for stress resistance and slowed aging?

    Science.gov (United States)

    Hamilton, Karyn L; Miller, Benjamin F

    2016-09-01

    Stress resistance is thought to contribute to slowed-aging, although cause and effect between the two is controversial. On October 30, 2015 researchers gathered at the Front Range Consortium on Stress Resistance and Slowed Aging in Fort Collins, CO, to discuss what the current evidence is that stress resistance imparts slowed aging. Included in that discussion was defining stress resistance, distinguishing if there are key stresses to which resistance imparts slowed aging, what models aid in our understanding of stress resistance and aging, and how to translate that knowledge into slowed aging treatment. The following article is a brief summary of that discussion and recommendations for moving forward. PMID:27268049

  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. 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...

  5. 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...

  6. 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

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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...

  12. 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

  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. 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

  15. Slow flow in channels with porous walls

    CERN Document Server

    Jensen, Kaare H

    2012-01-01

    We consider the slow flow of a viscous incompressible liquid in a channel of constant but arbitrary cross section shape, driven by non-uniform suction or injection through the porous channel walls. A similarity transformation reduces the Navier-Stokes equations to a set of coupled equations for the velocity potential in two dimensions. When the channel aspect ratio and Reynolds number are both small, the problem reduces to solving the biharmonic equation with constant forcing in two dimensions. With the relevant boundary conditions, determining the velocity field in a porous channels is thus equivalent to solving for the vertical displacement of a simply suspended thin plate under uniform load. This allows us to provide analytic solutions for flow in porous channels whose cross-section is e.g. a rectangle or an equilateral triangle, and provides a general framework for the extension of Berman flow (Journal of Applied Physics 24(9), p. 1232, 1953) to three dimensions.

  16. 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 ...

  17. 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

  18. 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.

  19. Analysis of binding heterogeneity.

    NARCIS (Netherlands)

    Nederlof, M.M.

    1992-01-01

    Binding heterogeneity, due to different functional groups on a reactive surface, plays an important role in the binding of small molecules or ions to many adsorbents, both in industrial processes and in natural environments. The binding heterogeneity is described by a distribution of affinity consta

  20. Analyzing radioligand binding data.

    Science.gov (United States)

    Motulsky, Harvey; Neubig, Richard

    2002-08-01

    Radioligand binding experiments are easy to perform, and provide useful data in many fields. They can be used to study receptor regulation, discover new drugs by screening for compounds that compete with high affinity for radioligand binding to a particular receptor, investigate receptor localization in different organs or regions using autoradiography, categorize receptor subtypes, and probe mechanisms of receptor signaling, via measurements of agonist binding and its regulation by ions, nucleotides, and other allosteric modulators. This unit reviews the theory of receptor binding and explains how to analyze experimental data. Since binding data are usually best analyzed using nonlinear regression, this unit also explains the principles of curve fitting with nonlinear regression.

  1. Perturbation Approaches for Exploring Protein Binding Site Flexibility to Predict Transient Binding Pockets.

    Science.gov (United States)

    Kokh, Daria B; Czodrowski, Paul; Rippmann, Friedrich; Wade, Rebecca C

    2016-08-01

    Simulations of the long-time scale motions of a ligand binding pocket in a protein may open up new perspectives for the design of compounds with steric or chemical properties differing from those of known binders. However, slow motions of proteins are difficult to access using standard molecular dynamics (MD) simulations and are thus usually neglected in computational drug design. Here, we introduce two nonequilibrium MD approaches to identify conformational changes of a binding site and detect transient pockets associated with these motions. The methods proposed are based on the rotamerically induced perturbation (RIP) MD approach, which employs perturbation of side-chain torsional motion for initiating large-scale protein movement. The first approach, Langevin-RIP (L-RIP), entails a series of short Langevin MD simulations, each starting with perturbation of one of the side-chains lining the binding site of interest. L-RIP provides extensive sampling of conformational changes of the binding site. In less than 1 ns of MD simulation with L-RIP, we observed distortions of the α-helix in the ATP binding site of HSP90 and flipping of the DFG loop in Src kinase. In the second approach, RIPlig, a perturbation is applied to a pseudoligand placed in different parts of a binding pocket, which enables flexible regions of the binding site to be identified in a small number of 10 ps MD simulations. The methods were evaluated for four test proteins displaying different types and degrees of binding site flexibility. Both methods reveal all transient pocket regions in less than a total of 10 ns of simulations, even though many of these regions remained closed in 100 ns conventional MD. The proposed methods provide computationally efficient tools to explore binding site flexibility and can aid in the functional characterization of protein pockets, and the identification of transient pockets for ligand design. PMID:27399277

  2. Slow light in tapered slot photonic crystal waveguide

    Institute of Scientific and Technical Information of China (English)

    WU Jun; LI YanPing; YANG ChuanChuan; PENG Chao; WANG ZiYu

    2009-01-01

    A slotted single-mode photonic crystal waveguide with a linear tapered slot is presented to realize slow light, whose dispersion curve is shifted by changing the slot width. When the slot width is reduced, the band curve shifts in the tapered structure, and the group velocity of light approach zero at the cut-off frequency. Therefore, different frequency components of the guided light are slowed down even loca-lized along the propagation direction inside a tapered slot photonic crystal waveguide. Furthermore, this structure can confine slow light-wave in a narrow slot waveguide, which may effectively enhance the interaction between slow light and the low-index wave-guiding materials filled in the slot. In addition, this tapered slot structure can be used to compensate group velocity dispersion of slow light by mod-ifying the structure, thus opening the opportunity for ultra-wide bandwidth slow light.

  3. Slow-roll approximation in loop quantum cosmology

    CERN Document Server

    Luc, Joanna

    2016-01-01

    The slow-roll approximation is an analytical approach to study dynamical properties of the inflationary universe. In this article, systematic construction of the slow-roll expansion for effective loop quantum cosmology is presented. The analysis is performed up to the fourth order in both slow-roll parameters and the parameter controlling the strength of deviation from the classical case. The expansion is performed for three types of the slow-roll parameters: Hubble slow-roll parameters, Hubble flow parameters and potential slow-roll parameters. An accuracy of the approximation is verified by comparison with the numerical phase space trajectories for the case with a massive potential term. The results obtained in this article may be helpful in the search for the subtle quantum gravitational effects with use of the cosmological data.

  4. Deciding about fast and slow decisions.

    Science.gov (United States)

    Croskerry, Pat; Petrie, David A; Reilly, James B; Tait, Gordon

    2014-02-01

    Two reports in this issue address the important topic of clinical decision making. Dual process theory has emerged as the dominant model for understanding the complex processes that underlie human decision making. This theory distinguishes between the reflexive, autonomous processes that characterize intuitive decision making and the deliberate reasoning of an analytical approach. In this commentary, the authors address the polarization of viewpoints that has developed around the relative merits of the two systems. Although intuitive processes are typically fast and analytical processes slow, speed alone does not distinguish them. In any event, the majority of decisions in clinical medicine are not dependent on very short response times. What does appear relevant to diagnostic ease and accuracy is the degree to which the symptoms of the disease being diagnosed are characteristic ones. There are also concerns around some methodological issues related to research design in this area of enquiry. Reductionist approaches that attempt to isolate dependent variables may create such artificial experimental conditions that both external and ecological validity are sacrificed. Clinical decision making is a complex process with many independent (and interdependent) variables that need to be separated out in a discrete fashion and then reflected on in real time to preserve the fidelity of clinical practice. With these caveats in mind, the authors believe that research in this area should promote a better understanding of clinical practice and teaching by focusing less on the deficiencies of intuitive and analytical systems and more on their adaptive strengths.

  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. 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...

  7. 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

  8. 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.

  9. 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

  10. 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

  11. 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

  12. Towards Modelling slow Earthquakes with Geodynamics

    Science.gov (United States)

    Regenauer-Lieb, K.; Yuen, D. A.

    2006-12-01

    We explore a new, properly scaled, thermal-mechanical geodynamic model{^1} that can generate timescales now very close to those of earthquakes and of the same order as slow earthquakes. In our simulations we encounter two basically different bifurcation phenomena. One in which the shear zone nucleates in the ductile field, and the second which is fully associated with elasto-plastic (brittle, pressure- dependent) displacements. A quartz/feldspar composite slab has all two modes operating simultaneously in three different depth levels. The bottom of the crust is predominantly controlled by the elasto-visco-plastic mode while the top is controlled by the elasto-plastic mode. The exchange of the two modes appears to communicate on a sub-horizontal layer in a flip-flop fashion, which may yield a fractal-like signature in time and collapses into a critical temperature which for crustal rocks is around 500-580 K; in the middle of the brittle-ductile transition-zone. Near the critical temperature, stresses close to the ideal strength can be reached at local, meter-scale. Investigations of the thermal-mechanical properties under such extreme conditions are pivotal for understanding the physics of earthquakes. 1. Regenauer-Lieb, K., Weinberg, R. & Rosenbaum, G. The effect of energy feedbacks on continental strength. Nature 442, 67-70 (2006).

  13. 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...... mechanism allows for the production of a constant flux of 4.5×106 atoms per second and due to transverse guiding we obtain an upper limit for the mean beam width of 4.6 μm. The transverse velocity spread is only 0.2 mm/s and thus an upper limit for the beam quality parameter is M 2=2.5. We demonstrate...... the potential of the long interrogation times available with this atom laser beam by measuring the trap frequency in a single measurement. The small beam width together with the long evolution and interrogation time makes this atom laser beam a promising tool for continuous interferometric measurements....

  14. Elemental building blocks of the slow solar wind

    Science.gov (United States)

    Kepko, L.; Viall, N. M.; Lepri, S. T.

    2014-12-01

    While the source of the fast solar wind is well understood to be linked to coronal holes, the source of the slow solar wind has remained elusive. A distinguishing characteristic of the slow solar wind is the high variability of the plasma parameters, such as magnetic field, velocity, density, composition, and charge state. Many previous studies of the slow solar wind have examined trends in the composition and charge states over long time scales and using data with comparatively low temporal resolution. In this study, we take advantage of high time resolution (12 min) measurements of the charge-state abundances recently reprocessed by the ACE SWICS science team to probe the timescales of solar wind variability of coherent structures at relatively small scales (<2000 Mm, or ~ 90 minutes at slow wind speeds). We use an interval of slow solar wind containing quasi pressure-balanced, periodic number density structures previously studied by Kepko et al and shown to be important in solar wind-magnetospheric coupling. The combination of high temporal resolution composition measurements and the clearly identified boundaries of the periodic structures allows us to probe the elemental slow solar wind flux tubes/structures. We use this train of 2000Mm periodic density structures as tracers of solar wind origin and/or acceleration. We find that each 2000 Mm parcel of slow solar wind, though its speed is steady, exhibits the complete range of charge state and composition variations expected for the entire range of slow solar wind, in a repeated sequence. Each parcel cycles through three states: 1) 'normal' slow wind, 2) compositionally slow wind with very high density, and 3) compositionally fast but typical slow solar wind density. We conclude by suggesting these structures form elemental building blocks of the slow solar wind, and discuss whether it is necessary to decouple separately the process(es) responsible for the release and acceleration.

  15. 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.

  16. 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...

  17. The Persistence of a Slow Manifold with Bifurcation

    DEFF Research Database (Denmark)

    Kristiansen, Kristian Uldall; Palmer, P.; Robert, M.

    2012-01-01

    his paper considers the persistence of a slow manifold with bifurcation in a slow-fast two degree of freedom Hamiltonian system. In particular, we consider a system with a supercritical pitchfork bifurcation in the fast space which is unfolded by the slow coordinate. The model system is motivated...... by tethered satellites. It is shown that an almost full measure subset of a neighborhood of the slow manifold's normally elliptic branches persists in an adiabatic sense. We prove this using averaging and a blow-up near the bifurcation....

  18. 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)

  19. 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.

  20. High prevalence of protein C, protein S, antithrombin deficiency, and Factor V Leiden mutation as a cause of hereditary thrombophilia in patients of venous thromboembolism and cerebrovascular accident

    Science.gov (United States)

    Ali, Nadir; Ayyub, Muhammad; Khan, Saleem Ahmed

    2014-01-01

    Objectives: To determine the frequency of Protein C, Protein S (PC & PS), antithrombin deficiency (AT III) and Factor V Leiden mutation (FVL) as a cause of thrombophilia in the patients with venous thromboembolism (VTE) and cerebrovascular accident (CVA). Methods: It was an observational study conducted at Department of Haematology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, Pakistan. All patients referred for thrombophilia screening from July 2009 to June 2012 were screened. Patients with evidence of VTE or CVA were screened for PC & PS, AT III deficiency, and FVL. Results: Total 404 patients of age between 1-71 years mean 33 ± 14 with male to female ratio of 2.4:1 had evidence of thrombophilia. Two hundred eighteen (54%) patients presented with CVA, 116 (29%) with deep vein thrombosis (DVT), 42 (10.5%) with pulmonary embolism (PE), and 28 (7.5%) with portal or mesenteric vein thrombosis (PV). Protein C & S deficiency was detected in 35/404 (8.7%), ATIII in 9/404 (2%), and FVL in 25/173 patients (14.5%). The findings were suggestive of a significant association of FVL mutation for developing DVT (OR=11.0, 95% C I 4.6-26.3), CVA (OR=5.7, 95% C I 2.1-15.1), and PV (OR=5.4, 95% C I 1.3-21.9). PC & PS deficiency was a significant risk factor for developing PE (OR=3, 95% C I 0.8-11.4). Conclusion: FVL mutation and Protein C & S are the leading causes of thrombophilia with strong association of Factor V Leiden mutation as risk for developing DVT. PMID:25674132

  1. 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

  2. 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.

  3. 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.

  4. New data on programmed aging - slow phenoptosis.

    Science.gov (United States)

    Skulachev, M V; Skulachev, V P

    2014-10-01

    indicating that aging can be regulated by an organism provide another argument in favor of optionality of aging. Cases have been described when aging as a program useful for the evolution of offspring but counterproductive for the parental individual slows under conditions that threaten the very existence of the individual. These conditions include food restriction (the threat of death from starvation), heavy muscular work, decrease or increase in the environmental temperature, small amounts of poisons (including ROS; here we speak about the paradoxical geroprotective effect of the low doses of prooxidants that inhibit apoptosis). On the other hand, aging can be inhibited (and maybe even cancelled) artificially. This can be done by turning off the genes encoding the proteins participating in the aging program, such as FAT10, p66shc, and some others. In addition, the gene of the antioxidant enzyme catalase can be addressed into mitochondria, where it will split mitochondrial hydrogen peroxide, the level of which increases with age. However, today the simplest way to slow down the aging program is the use of mitochondria-targeted low molecular weight antioxidant compounds of plastoquinonyl decyltriphenylphosphonium-type (SkQ1), which prolong the life of animals, plants, and fungi and inhibit the development of many age-related diseases and symptoms.

  5. 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).

  6. 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 ...

  7. 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

  8. 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.

  9. 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)...

  10. 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...

  11. 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)

  12. 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.

  13. 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

  14. Effects on coagulation and fibrinolysis induced by influenza in mice with a reduced capacity to generate activated protein C and a deficiency in plasminogen activator inhibitor type 1.

    Science.gov (United States)

    Keller, Tymen T; van der Sluijs, Koen F; de Kruif, Martijn D; Gerdes, Victor E A; Meijers, Joost C M; Florquin, Sandrine; van der Poll, Tom; van Gorp, Eric C M; Brandjes, Dees P M; Büller, Harry R; Levi, Marcel

    2006-11-24

    Influenza infections increase the risk of diseases associated with a prothrombotic state, such as venous thrombosis and atherothrombotic diseases. However, it is unclear whether influenza leads to a prothrombotic state in vivo. To determine whether influenza activates coagulation, we measured coagulation and fibrinolysis in influenza-infected C57BL/6 mice. We found that influenza increased thrombin generation, fibrin deposition, and fibrinolysis. In addition, we used various anti- and prothrombotic models to study pathways involved in the influenza-induced prothrombotic state. A reduced capacity to generate activated protein C in TM(pro/pro) mice increased thrombin generation and fibrinolysis, whereas treatment with heparin decreased thrombin generation in influenza-infected C57Bl/6 mice. Thrombin generation was not changed in hyperfibrinolytic mice, deficient in plasminogen activator inhibitor type-1 (PAI-1(-/-)); however, increased fibrin degradation was seen. Treatment with tranexamic acid reduced fibrinolysis, but thrombin generation was unchanged. We conclude that influenza infection generates thrombin, increased by reduced levels of protein C and decreased by heparin. The fibrinolytic system appears not to be important for thrombin generation. These findings suggest that influenza leads to a prothrombotic state by coagulation activation. Heparin treatment reduces the influenza induced prothrombotic state. PMID:17068293

  15. 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)

  16. 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.

  17. Identification of slow molecular order parameters for Markov model construction

    CERN Document Server

    Perez-Hernandez, Guillermo; Giorgino, Toni; de Fabritiis, Gianni; Noé, Frank

    2013-01-01

    A goal in the kinetic characterization of a macromolecular system is the description of its slow relaxation processes, involving (i) identification of the structural changes involved in these processes, and (ii) estimation of the rates or timescales at which these slow processes occur. Most of the approaches to this task, including Markov models, Master-equation models, and kinetic network models, start by discretizing the high-dimensional state space and then characterize relaxation processes in terms of the eigenvectors and eigenvalues of a discrete transition matrix. The practical success of such an approach depends very much on the ability to finely discretize the slow order parameters. How can this task be achieved in a high-dimensional configuration space without relying on subjective guesses of the slow order parameters? In this paper, we use the variational principle of conformation dynamics to derive an optimal way of identifying the "slow subspace" of a large set of prior order parameters - either g...

  18. 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.

  19. 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.

  20. Kinetic investigation for slow combustion of biomass

    Energy Technology Data Exchange (ETDEWEB)

    Haykiri-Acma, H.; Yaman, S. [Istanbul Technical Univ., Istanbul (Turkey). Dept. of Chemical Engineering, Faculty of Chemical and Metallurgical Engineering

    2006-07-01

    The renewed interest in biomass as a renewable, clean, and inexpensive fuel was discussed. Many different mechanisms take place simultaneously during biomass combustion and also during other thermal processes such as gasification, pyrolysis or carbonization. These mechanisms have a pronounced influence on the design and operation of thermal conversion processes. In addition, product yields and product distributions from the thermal processes are sensitive to the kinetic properties of biomass. In order to evaluate the combustion mechanisms and the combustion kinetics of biomass, the behavior of these constituents under combustion conditions were properly evaluated. In this study, combustion of biomass samples was carried out in a thermogravimetric analyzer by heating them from ambient to 1173 K with heating rates of 5 K/min and 10 K/min under dynamic dry air atmosphere of 40 mL/min. The biomass samples included olive refuse, sunflower seed shell, rapeseed, grape seed, and hybrid poplar. The purpose of the study was to examine the kinetic properties of biomass during slow combustion for the overall combustion process as well as for some definite temperature intervals at which different combustion mechanisms are present according to the type and complexity of biomass used. Derivative thermogravimetric analysis (DTG) curves were derived, and data obtained from these curves were used to compute the kinetic parameters such as activation energy, pre-exponential factor, and governing mechanisms for the combustion processes. The governing mechanisms for individual temperature intervals were examined along with the overall combustion process. The study showed that at lower temperature intervals, the combustion process was controlled primarily by the chemical reaction. At least 3 sequential mechanisms may occur at different temperature intervals during combustion of biomass. Activation energy and pre-exponential factors were determined for each temperature interval

  1. 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)

  2. 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.

  3. 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.

  4. Hedgehog can drive terminal differentiation of amniote slow skeletal muscle

    Directory of Open Access Journals (Sweden)

    Bildsoe Heidi

    2004-07-01

    Full Text Available Abstract Background Secreted Hedgehog (Hh signalling molecules have profound influences on many developing and regenerating tissues. Yet in most vertebrate tissues it is unclear which Hh-responses are the direct result of Hh action on a particular cell type because Hhs frequently elicit secondary signals. In developing skeletal muscle, Hhs promote slow myogenesis in zebrafish and are involved in specification of medial muscle cells in amniote somites. However, the extent to which non-myogenic cells, myoblasts or differentiating myocytes are direct or indirect targets of Hh signalling is not known. Results We show that Sonic hedgehog (Shh can act directly on cultured C2 myoblasts, driving Gli1 expression, myogenin up-regulation and terminal differentiation, even in the presence of growth factors that normally prevent differentiation. Distinct myoblasts respond differently to Shh: in some slow myosin expression is increased, whereas in others Shh simply enhances terminal differentiation. Exposure of chick wing bud cells to Shh in culture increases numbers of both muscle and non-muscle cells, yet simultaneously enhances differentiation of myoblasts. The small proportion of differentiated muscle cells expressing definitive slow myosin can be doubled by Shh. Shh over-expression in chick limb bud reduces muscle mass at early developmental stages while inducing ectopic slow muscle fibre formation. Abundant later-differentiating fibres, however, do not express extra slow myosin. Conversely, Hh loss of function in the limb bud, caused by implanting hybridoma cells expressing a functionally blocking anti-Hh antibody, reduces early slow muscle formation and differentiation, but does not prevent later slow myogenesis. Analysis of Hh knockout mice indicates that Shh promotes early somitic slow myogenesis. Conclusions Taken together, the data show that Hh can have direct pro-differentiative effects on myoblasts and that early-developing muscle requires Hh for

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. NMR detection of slow conformational dynamics in an endonuclease toxin

    Energy Technology Data Exchange (ETDEWEB)

    Whittaker, Sara B.-M.; Boetzel, Ruth; MacDonald, Colin [University of East Anglia, School of Chemical Sciences (United Kingdom); Lian Luyun [Leicester University, Biological NMR Centre (United Kingdom); Pommer, Ansgar J. [University of East Anglia, School of Biological Sciences (United Kingdom); Reilly, Ann; James, Richard; Kleanthous, Colin [Leicester University, Biological NMR Centre (United Kingdom); Moore, Geoffrey R. [University of East Anglia, School of Chemical Sciences (United Kingdom)

    1998-07-15

    The cytotoxic activity of the secreted bacterial toxin colicin E9 is due to a non-specific DNase housed in the C-terminus of the protein. Double-resonance and triple-resonance NMR studies of the 134-amino acid{sup 15} N- and {sup 13}C/{sup 15}N-labelled DNase domain are presented. Extensive conformational heterogeneity was evident from the presence of far more resonances than expected based on the amino acid sequence of the DNase, and from the appearance of chemical exchange cross-peaks in TOCSY and NOESY spectra. EXSY spectra were recorded to confirm that slow chemical exchange was occurring. Unambiguous sequence-specific resonance assignments are presented for one region of the protein, Pro{sup 65}-Asn{sup 72}, which exists in two slowly exchanging conformers based on the identification of chemical exchange cross-peaks in 3D {sup 1}H-{sup 1}H-{sup 15}N EXSY-HSQC, NOESY-HSQC and TOCSY-HSQC spectra, together with C{sup {alpha}} and C{sup {beta}} chemical shifts measured in triple-resonance spectra and sequential NH NOEs. The rates of conformational exchange for backbone amide resonances in this stretch of amino acids, and for the indole NH of either Trp{sup 22} or Trp{sup 58}, were determined from the intensity variation of the appropriate diagonal and chemical exchange cross-peaks recorded in 3D{sup 1} H-{sup 1}H-{sup 15}N NOESY-HSQC spectra. The data fitted a model in which this region of the DNase has two conformers, N{sub A} and N{sub B}, which interchange at 15 {sup o}C with a forward rate constant of 1.61 {+-} 0.5 s{sup -1} and a backward rate constant of 1.05 {+-} 0.5 s{sup -1}. Demonstration of this conformational equilibrium has led to a reappraisal of a previously proposed kinetic scheme describing the interaction of E9 DNase with immunity proteins [Wallis et al. (1995) Biochemistry, 34, 13743-13750 and 13751-13759]. The revised scheme is consistent with the specific inhibitor protein for the E9 DNase, Im9, associating with both the N{sub A} and N{sub B

  10. 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.

  11. 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 ...

  12. Endothelial cell protein C receptor gene 6936A/G and 4678G/C polymorphisms as risk factors for deep venous thrombosis.

    Science.gov (United States)

    Zoheir, Naguib; Eldanasouri, Nabiel; Abdel-Aal, Asmaa A; Hosny, Karim Adel; Abdel-Ghany, Wafaa M

    2016-04-01

    Endothelial cell protein C receptor (EPCR) enhances the generation of activated protein C by the thrombin-thrombomodulin complex. A soluble form of EPCR (sEPCR) is present in plasma. Two polymorphisms in the EPCR gene (6936A/G and 4678G/C) have been reported to influence the risk of venous thromboembolism. We aimed to investigate the relation between EPCR gene polymorphisms (6936A/G and 4678C/G) and deep venous thrombosis (DVT) and their relations to sEPCR level. This study involved 90 patients with DVT and 90 age and sex-matched healthy controls. Plasma levels of sEPCR were measured in 45 cases of the primary DVT by ELISA. PCR-restriction fragment length polymorphism (RFLP) was used for detection of EPCR polymorphisms (6936A/G and 4678G/C). Regarding 6936A/G, our results demonstrated that mutant genotypes (AG, GG) were associated with an increased risk for DVT [P mutant allele G (P mutant genotypes were associated with increased levels of sEPCR. Although in 4678G/C, our results demonstrated that the mutant genotype (CC) was considered as a protective factor against DVT (P = 0.014, OR 0.289, 95% CI 0.108-0.776) as well as its mutant allele C (P = 0.02, OR 0.600, 95% CI 0.388-0.927), but it had no effect on sEPCR level. Our data suggest that 6936A/G polymorphism is a risk factor for DVT and is associated with elevated plasma levels of sEPCR, while 4678G/C polymorphism plays a role in protection against DVT. PMID:26340463

  13. Optimum Multiuser Detector for Multipath Slow Fading Asynchronous CDMA Channels

    Institute of Scientific and Technical Information of China (English)

    WangZhaocheng; YangZhixing; 等

    1995-01-01

    A structure of optimum multiuser detector for asynchronous CDMA in multipath slow fading channels is derived and the significant performance gain over the conventional RAKE receiv-er is shown by simulation.

  14. THE BRIDGE STRUCTURE TESTS UNDER SLOW MOVING LOAD

    Directory of Open Access Journals (Sweden)

    B. D. Sukhorukov

    2010-03-01

    Full Text Available Peculiarities and advantages of bridge structure tests under slow moving load are pointed out. The calculation algorithms for finding in-situ influence line ordinates based on the results of the tests are proposed.

  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. 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 ...

  17. Compounding of slow-release niacinamide capsules: feasibility and characterization.

    Science.gov (United States)

    Radojkovic, Branko; Milić, Jela; Calija, Bojan

    2012-01-01

    The purpose of this study was to assess the feasibility of extemporaneous compounding of slow-release oral dosage form of niacinamide and to evaluate its release kinetics. The model formulation (preparation) was developed in the form of powder-filled hard gelatin capsules. Two slow-release preparations with different ratios of hypromellose have been prepared and evaluated in comparison with an immediate-release preparation. The dissolution tests were performed as per United States Pharmacopoeia requirements: Type I Apparatus, over 7 hours. Both slow-release preparations, containing 40% and 60% v/v hypromellose, respectively, have showed slow release kinetics. The dissolution profiles were significantly different, with similarity factor f2niacinamide capsules can be successfully compounded using hypromellose as a sole release rate modifier, and that the release mechanism is comparable to hydrophilic polymer matrix-based systems.

  18. 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

  19. Slow light enhancement and limitations in periodic media

    DEFF Research Database (Denmark)

    Grgic, Jure

    Properties of periodic dielectric media have attracted a big interest in the last two decades due to numerous exciting physical phenomena that cannot occur in homogeneous media. Due to their strong dispersive properties, the speed of light can be significantly slowed down in periodic structures...... on 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...... to longer interaction time in the periodic media. Due to this reason, weak light-matter interaction is enhanced. The enhancement due to slow light has been studied for loss and gain. By introducing gain/loss, dispersive properties, in the slow light region, are severely influenced. The minimum attainable...

  20. 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...... of the 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...

  1. 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.

  2. 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.)

  3. 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.)

  4. 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...

  5. 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...

  6. 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)

  7. 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...

  8. Slow light in semiconductor waveguides: Theory and experiment

    DEFF Research Database (Denmark)

    Mørk, Jesper; Öhman, Filip; Poel, Mike van der;

    2007-01-01

    Slow light in multi-section quantum well waveguide structure is realized using either coherent population oscillations (CPO) and electromagnetically induced transparency (EIT) is studied. The properties of the two schemes are compared and discussed.......Slow light in multi-section quantum well waveguide structure is realized using either coherent population oscillations (CPO) and electromagnetically induced transparency (EIT) is studied. The properties of the two schemes are compared and discussed....

  9. 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....

  10. 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....

  11. 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 ...

  12. Global intracellular slow-wave dynamics of the thalamocortical system.

    Science.gov (United States)

    Sheroziya, Maxim; Timofeev, Igor

    2014-06-25

    It is widely accepted that corticothalamic neurons recruit the thalamus in slow oscillation, but global slow-wave thalamocortical dynamics have never been experimentally shown. We analyzed intracellular activities of neurons either from different cortical areas or from a variety of specific and nonspecific thalamic nuclei in relation to the phase of global EEG signal in ketamine-xylazine anesthetized mice. We found that, on average, slow-wave active states started off within frontal cortical areas as well as higher-order and intralaminar thalamus (posterior and parafascicular nuclei) simultaneously. Then, the leading edge of active states propagated in the anteroposterior/lateral direction over the cortex at ∼40 mm/s. The latest structure we recorded within the slow-wave cycle was the anterior thalamus, which followed active states of the retrosplenial cortex. Active states from different cortical areas tended to terminate simultaneously. Sensory thalamic ventral posterior medial and lateral geniculate nuclei followed cortical active states with major inhibitory and weak tonic-like "modulator" EPSPs. In these nuclei, sharp-rising, large-amplitude EPSPs ("drivers") were not modulated by cortical slow waves, suggesting their origin in ascending pathways. The thalamic active states in other investigated nuclei were composed of depolarization: some revealing "driver"- and "modulator"-like EPSPs, others showing "modulator"-like EPSPs only. We conclude that sensory thalamic nuclei follow the propagating cortical waves, whereas neurons from higher-order thalamic nuclei display "hub dynamics" and thus may contribute to the generation of cortical slow waves.

  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. 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

  15. Retinoic acid binding protein in normal and neopolastic rat prostate.

    Science.gov (United States)

    Gesell, M S; Brandes, M J; Arnold, E A; Isaacs, J T; Ueda, H; Millan, J C; Brandes, D

    1982-01-01

    Sucrose density gradient analysis of cytosol from normal and neoplastic rat prostatic tissues exhibited a peak of (3H) retinoic acid binding in the 2S region, corresponding to the cytoplasmic retinoic acid binding protein (cRABP). In the Fisher-Copenhagen F1 rat, cRABP was present in the lateral lobe, but could not be detected in the ventral nor in the dorsal prostatic lobes. Four sublines of the R-3327 rat prostatic tumor contained similar levels of this binding protein. The absence of cRABP in the normal tissue of origin of the R-3327 tumor, the rat dorsal prostate, and reappearance in the neoplastic tissues follows a pattern described in other human and animal tumors. The occurrence of cRABP in the well-differentiated as well as in the anaplastic R-3327 tumors in which markers which reflect a state of differentiation and hormonal regulation, such as androgen receptor, 5 alpha reductase, and secretory acid phosphatase are either markedly reduced or absent, points to cRABP as a marker of malignant transformation.

  16. 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

  17. 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.

  18. 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

  19. 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...

  20. 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...... and 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...

  1. Oligoarginine peptides slow strand annealing and assist non-enzymatic RNA replication

    Science.gov (United States)

    Jia, Tony Z.; Fahrenbach, Albert C.; Kamat, Neha P.; Adamala, Katarzyna P.; Szostak, Jack W.

    2016-10-01

    The non-enzymatic replication of RNA is thought to have been a critical process required for the origin of life. One unsolved difficulty with non-enzymatic RNA replication is that template-directed copying of RNA results in a double-stranded product. After strand separation, rapid strand reannealing outcompetes slow non-enzymatic template copying, which renders multiple rounds of RNA replication impossible. Here we show that oligoarginine peptides slow the annealing of complementary oligoribonucleotides by up to several thousand-fold; however, short primers and activated monomers can still bind to template strands, and template-directed primer extension can still occur, all within a phase-separated condensed state, or coacervate. Furthermore, we show that within this phase, partial template copying occurs even in the presence of full-length complementary strands. This method to enable further rounds of replication suggests one mechanism by which short non-coded peptides could have enhanced early cellular fitness, and potentially explains how longer coded peptides, that is, proteins, came to prominence in modern biology.

  2. Mechanical and Acoustic Signature of Slow Earthquakes on Laboratory Faults

    Science.gov (United States)

    Scuderi, Marco Maria; Marone, Chris; Tinti, Elisa; Scognamiglio, Laura; Di Stefano, Giuseppe; Collettini, Cristiano

    2015-04-01

    Recent seismic and geodetic observations show that fault slip occurs via a spectrum of behaviors that range from seismic (fast dynamic) to aseismic (creep). Indeed faults can slip via a variety of quasi-dynamic processes such as Slow-Slip, Low Frequency Earthquakes (LFE), and Tremor. These transient modes of slip represent slow, but self-propagating acceleration of slip along fault zones. These phenomena have been observed worldwide in a variety of active tectonic environments, however the physics of quasi-dynamic rupture and the underlying fault zone processes are still poorly understood. Rate- and State- frictional constitutive equations predict that fast dynamic slip will occur when the stiffness of the loading system (k) is less than a critical stiffness (kc) characterizing the fault gouge. In order to investigate quasi-dynamic transients, we performed laboratory experiments on simulated fault gouge (silica powders) in the double direct shear configuration with a compliant central block allowing boundary conditions where k≈kc. In addition, PZTs were used to measure acoustical properties of the gouge layers during shear. We document an evolution of the fault mechanical properties as the σn is increased. For σn < 10 MPa we observe a steady state frictional type of shear. When σn ≥ 15 MPa we observe emergent slow-slip events from steady state shear with accumulated shear displacement of about 10 mm. The typical values of stress drop (Δτ) vary between 0.2 and 0.8 MPa, and have typical duration from 0.5 up to 3 seconds giving the characteristics of slow stick-slip. As σn is varied we observe different characteristics of slow slip. For σn = 15MPa a repetitive double period oscillation is observed with slow slip growing until a maximum stress drop and then self attenuating. When σn is increased to 20 and 25 MPa slow slip are characterized by larger Δτ with constant τmax and τmin, however still showing a co-seismic duration of ~2 seconds. Our results

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. Advances in Bichromatic Force Slowing of Atoms and Molecules

    Science.gov (United States)

    Chieda, M. A.; Eyler, E. E.

    2012-06-01

    The optical bichromatic force (BCF) holds promise as an efficient, simple, and compact means to slow atoms and molecules to MOT capture velocities.ootnotetextM. Cashen and H. Metcalf, JOSA B 20, 915 (2003).^,ootnotetextM. A. Chieda and E. E. Eyler, PRA 84, 063401 (2011). Metastable helium beams, with v˜1000 m/s, are especially worthwhile atomic candidates since they presently require Zeeman slowers with lengths of 2--3 m. We present a novel BCF decelerator in which the Doppler shifts are chirped to keep the force centered on the atoms as they slow. This is made possible by recent advances in high-power diode lasers and electronics, and avoids many of the problems of alternative designs using large detunings. Initial tests on He* atoms show encouraging results. Unlike atoms, direct laser slowing of molecules remains exceedingly difficult, although success with SrF has very recently been reported.ootnotetextJ. F. Barry, E. S. Shuman, E. B. Norrgard, and D. DeMille, to be published. We calculate that for molecules with near-cycling transitions, rapid laser BCF slowing should be possible.ootnotetextChieda, op. sit. For the CaF molecule, we predict slowing by δv = 150 m/s, enough to bring a buffer-gas cooled beam to rest. An experimental demonstration is in progress.

  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. 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

  10. Semiclassical approximations for adiabatic slow-fast systems

    CERN Document Server

    Teufel, Stefan

    2012-01-01

    In this letter we give a systematic derivation and justification of the semiclassical model for the slow degrees of freedom in adiabatic slow-fast systems first found by Littlejohn and Flynn [5]. The classical Hamiltonian obtains a correction due to the variation of the adiabatic subspaces and the symplectic form is modified by the curvature of the Berry connection. We show that this classical system can be used to approximate quantum mechanical expectations and the time-evolution of operators also in sub-leading order in the combined adiabatic and semiclassical limit. In solid state physics the corresponding semiclassical description of Bloch electrons has led to substantial progress during the recent years, see [1]. Here, as an illustration, we show how to compute the Piezo-current arising from a slow deformation of a crystal in the presence of a constant magnetic field.

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

    DEFF Research Database (Denmark)

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

    2001-01-01

    tetranectin protein is retained, we examined the distribution of tetranectin in various muscle types in chicken. Myofibers strongly positive for tetranectin were observed in several muscles including m. tibialis ant. and m. sartorius (from embryonic day 10 to adult). Using antibodies to fast and slow myosin......Tetranectin is a C-type lectin that occurs in the mammalian musculoskeletal system. In the present report we describe the first studies on an avian tetranectin. A full-length chicken tetranectin cDNA was isolated. Comparison of the deduced amino acid sequence of chicken tetranectin with mouse...... 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...

  12. Rotigaptide (ZP123) reverts established atrial conduction velocity slowing.

    Science.gov (United States)

    Haugan, Ketil; Kjølbye, Anne Louise; Hennan, James K; Petersen, Jørgen Søberg

    2005-01-01

    Rotigaptide (ZP123) increases gap junction intercellular communication (GJIC) and prevents stress-induced cardiac conduction velocity (CV) slowing. However, the effect of rotigaptide on established cardiac conduction slowing and the duration of effect on rotigaptide during washout is unknown. Metabolic stress (induced by superfusion with nonoxygenated glucose-free Tyrodes buffer) was associated with a 30% decrease in atrial CV in vehicle-treated rat atria. Rotigaptide treatment initiated after a period of 30 minutes of metabolic stress produced a rapid and significant increase in CV compared to vehicle-treated time controls. During washout of rotigaptide for 30 min (while subjected to metabolic stress), there was a minor decrease in atrial CV; however, this was not significantly different from atrial CV in a rotigaptide-treated time control group. Rotigaptide treatment rapidly normalizes established conduction slowing in atria subjected to metabolic stress. However, the cessation of effect was considerably slower than the onset of action.

  13. A REVIEW OF SLOW SPEED BEARING DIAGNOSTICS AND PROGNOSTICS

    Directory of Open Access Journals (Sweden)

    SYLVESTER A. AYE

    2014-10-01

    Full Text Available This paper reviews the literature in diagnostics and prognostics of slow rotating bearings. Diagnostics and prognostics involve data acquisition and processing. The diagnostics and prognostics of rotating machinery is a subject of much on-going research. There are three approaches to diagnostics and prognostics which include data driven techniques, model based techniques and experience based approach. The review looks at current diagnostics and prognostics approaches to bearings in general and slow rotating bearings in particular and future trends. Bayesian techniques are currently gaining widespread application in diagnostics and prognostics of slow rotating bearings and mechanical systems as a result of their ability to handle the stochastic nature of the data well at varying operating conditions.

  14. 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...

  15. 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.

  16. 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

  17. 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.

  18. 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...

  19. Transmural myocardial ischemia due to slow coronary flow

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Slow coronary flow phenomenon(SCFP) is an angiographic observation characterized by delayed distal vessel opacification in the absence of significant epicardial coronary disease. Only limited studies have been focused on the etiologies, clinical manifestations and treatment of this unique angiographic phenomenon. In our case report, we described an 85-year-old man who came with significant ST segment elevation in leads V1-V4 and V3R-V5R without increase in myocardial enzyme. The patient also developed respiratory failure requiring intubation and mechanical ventilation. Coronary angiography revealed only mild atherosclerosis without spasm or thromboembolic occlusion. Slow flow was seen in all coronary arteries, especially in the left anterior descending and right coronary arteries. This case speculated that transmural myocardial ischemia with ST segment elevation might be resulted from slow coronary flow. Transmural myocardial ischemia can occur owing to abnormalities of the coronary microcirculation.

  20. 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...

  1. 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

  2. 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...

  3. 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.

  4. Cellulose binding domain proteins

    Energy Technology Data Exchange (ETDEWEB)

    Shoseyov, Oded (Karmey Yosef, IL); Shpiegl, Itai (Rehovot, IL); Goldstein, Marc (Davis, CA); Doi, Roy (Davis, CA)

    1998-01-01

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production thereof. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques.

  5. 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.

  6. Lectin binding in meningiomas.

    Science.gov (United States)

    Kleinert, R; Radner, H

    1987-01-01

    Forty-two meningiomas of different morphological sub-type were examined to determine their pattern of binding to 11 different lectins which characterize cell surface components such as carbohydrate residues. Histiocytic and xanthoma cells within meningiomas could be demonstrated with six different lectins: wheat germ agglutinin (WGA), peanut agglutinin (PNA) Bauhinia purpurea agglutinin (BPA), Helix pomatia agglutinin (HPA), Vicia fava agglutinin (VFA) and Soyabean agglutinin (SBA). Vascular elements including endothelial cells and intimal cells, bound Ulex europaeus agglutinin type 1 (UEA 1), WGA and HPA. The fibrous stroma in fibrous and fibroblastic meningiomas bound PNA, Laburnum alpinum agglutinin (LAA) and SBA. Tumour cells in meningotheliomatous meningiomas and some areas of anaplastic meningiomas bound Concanavalin A, PNA, LAA and VFA whereas tumour cells in fibrous and fibroblastic meningiomas bound BPA, LAA and VFA. Lectin binding has proved to be of value in detecting histiocytic and xanthoma cells together with vascular elements within meningiomas. In addition, the different lectin binding patterns allow different histological sub-types of meningioma to be distinguished although the biological significance of the binding patterns is unclear. PMID:3658105

  7. 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.

  8. Structural effects of pH and deacylation on surfactant protein C in an organic solvent mixture: a constant-pH MD study.

    Science.gov (United States)

    Carvalheda, Catarina A; Campos, Sara R R; Machuqueiro, Miguel; Baptista, António M

    2013-11-25

    The pulmonary surfactant protein C (SP-C) is a small highly hydrophobic protein that adopts a mainly helical structure while associated with the membrane but misfolds into a β-rich metastable structure upon deacylation, membrane dissociation, and exposure to the neutral pH of the aqueous alveolar subphase, eventually leading to the formation of amyloid aggregates associated with pulmonary alveolar proteinosis. The present constant-pH MD study of the acylated and deacylated isoforms of SP-C in a chloroform/methanol/water mixture, often used to mimic the membrane environment, shows that the loss of the acyl groups has a structural destabilizing effect and that the increase of pH promotes intraprotein contacts which contribute to the loss of helical structure in solution. These contacts result from the poor solvation of charged groups by the solvent mixture, which exhibits a limited membrane-mimetic character. Although a single SP-C molecule was used in the simulations, we propose that analogous intermolecular interactions may play a role in the early stages of the protein misfolding and aggregation in this mixture.

  9. Cyclin-dependent kinase 2 phosphorylates s/t-p sites in the hepadnavirus core protein C-terminal domain and is incorporated into viral capsids.

    Science.gov (United States)

    Ludgate, Laurie; Ning, Xiaojun; Nguyen, David H; Adams, Christina; Mentzer, Laura; Hu, Jianming

    2012-11-01

    Phosphorylation of the hepadnavirus core protein C-terminal domain (CTD) is important for viral RNA packaging, reverse transcription, and subcellular localization. Hepadnavirus capsids also package a cellular kinase. The identity of the host kinase that phosphorylates the core CTD or gets packaged remains to be resolved. In particular, both the human hepatitis B virus (HBV) and duck hepatitis B virus (DHBV) core CTDs harbor several conserved serine/threonine-proline (S/T-P) sites whose phosphorylation state is known to regulate CTD functions. We report here that the endogenous kinase in the HBV capsids was blocked by chemical inhibitors of the cyclin-dependent kinases (CDKs), in particular, CDK2 inhibitors. The kinase phosphorylated the HBV CTD at the serine-proline (S-P) sites. Furthermore, we were able to detect CDK2 in purified HBV capsids by immunoblotting. Purified CDK2 phosphorylated the S/T-P sites of the HBV and DHBV CTD in vitro. Inhibitors of CDKs, of CDK2 in particular, decreased both HBV and DHBV CTD phosphorylation in vivo. Moreover, CDK2 inhibitors blocked DHBV CTD phosphorylation, specifically at the S/T-P sites, in a mammalian cell lysate. These results indicate that cellular CDK2 phosphorylates the functionally critical S/T-P sites of the hepadnavirus core CTD and is incorporated into viral capsids.

  10. Partial Characterisation of Salmonella gallinarum Clinical Isolate and Expression of Its Antigenic Outer Membrane Protein C (OmpC Gene In Planta

    Directory of Open Access Journals (Sweden)

    Ee Leen Pang

    2015-05-01

    Full Text Available Fowl typhoid’s epidemiology and disease intervention have been extensively studied since 1950's owing to its high mortality and morbidity rates. Even up-to-date, outbreaks are incessantly haunting poultry industries of major continents. Salmonella gallinarum, the etiologic agent of fowl typhoid, was used to develop a series of vaccination regime. However, treatments are gradually losing effectiveness due to residual virulence from mutated strains and rapid evolution of multi-drug resistance isolates. Hence, in planta subunit vaccine production is proposed to surpass current limitations. The homotrimeric osmoporin (outer membrane protein C is a potent candidate antigen that confers momentous stimulation of humoral and cell-mediated immune responses in broilers. This research signified the potential development of a plant-expressed OmpC immunogen. The project scope embarked on the identification of S. gallinarum clinical isolate, construction of expression cassette and delivery of constructs into Nicotiana benthamiana via agroinfiltration. The OmpC transcripts and proteins were detected successfully at the molecular weights of ~1.002 kbp and ~35 kDa, respectively. These preliminary findings pave the feasibility of biomanufacturing a safe and cost-effective fowl typhoid vaccine that would confer multi-protection against other significant Salmonella infections attributed to the high sequence homology of the OmpC gene. Speed improvement is demonstrated and transient expression appears to outperform conventional platforms in expediting vaccine production for an emerging pandemic strain.

  11. 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.

  12. 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.

  13. Anticoagulant response to Agkistrodon contortrix venom (ACV test): a new global test to screen for defects in the anticoagulant protein C pathway.

    Science.gov (United States)

    Robert, A; Eschwège, V; Hameg, H; Drouet, L; Aillaud, M F

    1996-04-01

    As specific assays used to identify defects in the protein C (PC) anticoagulant pathway are laborious and expensive, we describe here a global test to screen for these defects. This assay is expressed as the ratio of two activated partial thromboplastin times, one in the absence and one in the presence of 0,125 U/ml of the PC activator of Agkistrodon contortrix venom (ACV). Eight of the 168 healthy volunteers of the control group exhibited an ACV ratio below the lower normal limit of 3.37 [6 subjects with the mutation Arg 506 to Gln in their factor V gene (FV R506Q) and one with PS deficiency]. 128 patients who have had at least one episode of deep-vein thrombosis were retrospectively studied. All patients carrying FV Q506R (n = 48), PC deficiency (n = 14) or combined defects, i.e. FV Q506R and PC deficiency (n = 4) or FV Q506R and PS deficiency (n = 3), had ACV ratios ACV ratios which overlapped normal range. ACV ratios of one out of seven patients with antithrombin deficiency, and 10% of patients without identified defect in the PC anticoagulant pathway (n = 30) were ACV ratio raised to 3.70 could lead to a test identifying all patients with a defect in the PC anticoagulant pathway.

  14. Slow light in paraffin-coated Rb vapor cells

    CERN Document Server

    Klein, M; Phillips, D F; Walsworth, R L

    2006-01-01

    We present preliminary results from an experimental study of slow light in anti-relaxation-coated Rb vapor cells, and describe the construction and testing of such cells. The slow ground state decoherence rate allowed by coated cell walls leads to a dual-structured electromagnetically induced transparency (EIT) spectrum with a very narrow (<100 Hz) transparency peak on top of a broad pedestal. Such dual-structure EIT permits optical probe pulses to propagate with greatly reduced group velocity on two time scales. We discuss ongoing efforts to optimize the pulse delay in such coated cell systems.

  15. On Slow-roll Glueball Inflation from Holography

    CERN Document Server

    Anguelova, Lilia

    2016-01-01

    We investigate glueball inflation model-building via the methods of the gauge/gravity duality. For that purpose, we consider a certain 5d consistent truncation of type IIB supergravity. This theory admits a solution, whose metric is of the form of a $dS_4$ fibration over a fifth dimension. We find a new time-dependent deformation around this solution, which allows for a small $\\eta$ parameter of the corresponding inflationary model. This resolves a problem with a previous solution that allowed only $\\eta$ of order one and thus gave only an ultra-slow roll regime, but not regular slow roll.

  16. Slow wave ion heating in the HELIX helicon source

    Energy Technology Data Exchange (ETDEWEB)

    Kline, J L; Scime, E E; Boivin, R F; Keesee, A M; Sun, X [Physics Department, West Virginia University, Morgantown, WV 26505 (United States)

    2002-11-01

    Ion temperature measurements have been made at multiple axial and radial locations in a helicon source for a range of magnetic field strengths and RF frequencies. The observed temperature gradient along the axis suggests limited thermal transport along the magnetic field. The radial profiles are flat near the axis and in some cases peak near the edge of the plasma. The ion temperature measurements combined with calculations of the perpendicular wave numbers for the slow wave or 'Trivelpiece-Gould' mode are consistent with ion heating due to ion Landau damping of the slow wave at the edge of the plasma.

  17. 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

  18. 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...

  19. 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.

  20. 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...

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

    DEFF Research Database (Denmark)

    Ek, Sara; Hansen, Per Lunnemann; Chen, Yaohui;

    2014-01-01

    Passive photonic crystals have been shown to exhibit a multitude of interesting phenomena, including slow-light propagation in line-defect waveguides. It was suggested that by incorporating an active material in the waveguide, slow light could be used to enhance the effective gain of the material......, which would have interesting application prospects, for example enabling ultra-compact optical amplifiers for integration in photonic chips. Here we experi- mentally investigate the gain of a photonic crystal membrane structure with embedded quantum wells. We find that by solely changing the photonic...... to those realized in state-of-the-art semiconductor optical amplifiers should be attainable in compact photonic integrated amplifiers...

  2. 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 ...

  3. Steady state kinetic model for the binding of substrates and allosteric effectors to Escherichia coli phosphoribosyl-diphosphate synthase

    DEFF Research Database (Denmark)

    Willemoës, Martin; Hove-Jensen, Bjarne; Larsen, Sine

    2000-01-01

    saturation with ribose 5-phosphate leads to the binding of Mg2+ and substrates via a slow pathway where Pi binds to the enzyme last. The random mechanism for Pi binding was further supported by studies with competitive inhibitors of Mg2+, MgATP, and ribose 5-phosphate that all appeared noncompetitive when...... varying Pi at either saturating or unsaturating ribose 5-phosphate concentrations. Furthermore, none of the inhibitors induced inhibition at increasing Pi concentrations. Results from ADP inhibition of Pi activation suggest that these effectors compete for binding to a common regulatory site....

  4. 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…

  5. 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...

  6. 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

  7. 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.)

  8. 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.

  9. 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...

  10. Standing Shocks in the Inner Slow Solar Wind

    Institute of Scientific and Technical Information of China (English)

    LI Bo; CHEN Yan-Jun; LI Xing

    2011-01-01

    @@ We examine whether the flow tube along the edge of a coronal streamer supports standing shocks in the inner slow wind by solving an isothermal wind model in terms of the Lambert W function.It is shown that solutions with standing shocks do exist and they exist in a broad area in the parameter space characterizing the wind temperature and flow tube.In particular,streamers with cusps located at a heliocentric distance(>~)3.2R⊙ can readily support discontinuous slow winds with temperatures barely higher than 1 MK.%We examine whether the flow tube along the edge of a coronal streamer supports standing shocks in the inner slow wind by solving an isothermal wind model in terms of the Lambert W function. It is shown that solutions with standing shocks do exist and they exist in a broad area in the parameter space characterizing the wind temperature and flow tube. In particular, streamers with cusps located at a heliocentric distance (>) 3.2P⊙ can readily support discontinuous slow winds with temperatures barely higher than 1 MK.

  11. 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

  12. 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.

  13. 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.

  14. Slow light in quantum dot photonic crystal waveguides

    DEFF Research Database (Denmark)

    Nielsen, Torben Roland; Lavrinenko, Andrei; Mørk, Jesper

    2009-01-01

    A theoretical analysis of pulse propagation in a semiconductor quantum dot photonic crystal waveguide in the regime of electromagnetically induced transparency is presented. The slow light mechanism considered here is based on both material and waveguide dispersion. The group index n...

  15. Reduction in slow intercompartmental clearance of urea during dialysis

    Energy Technology Data Exchange (ETDEWEB)

    Bowsher, D.J.; Krejcie, T.C.; Avram, M.J.; Chow, M.J.; Del Greco, F.; Atkinson, A.J. Jr.

    1985-04-01

    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.

  16. Delineating psychomotor slowing from reduced processing speed in schizophrenia

    NARCIS (Netherlands)

    Morrens, M.; Hulstijn, W.; Matton, C.; Madani, Y.; Bouwel, L. van; Peuskens, J.; Sabbe, B.G.C.

    2008-01-01

    Introduction. Psychomotor slowing is an intrinsic feature of schizophrenia that is poorly delineated from generally reduced processing speed. Although the Symbol Digit Substitution Test (SDST) is widely used to assess psychomotor speed, the task also taps several higher-order cognitive processes. Re

  17. 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...

  18. 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…

  19. 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]…

  20. TANGO standard software to control the Nuclotron beam slow extraction

    Science.gov (United States)

    Andreev, V. A.; Volkov, V. I.; Gorbachev, E. V.; Isadov, V. A.; Kirichenko, A. E.; Romanov, S. V.; Sedykh, G. S.

    2016-09-01

    TANGO Controls is a basis of the NICA control system. The report describes the software which integrates the Nuclotron beam slow extraction subsystem into the TANGO system of NICA. Objects of control are power supplies for resonance lenses. The software consists of the subsystem device server, remote client and web-module for viewing the subsystem data.

  1. 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...

  2. 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 th...

  3. 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.

  4. 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

  5. Systematic design of slow-light photonic waveguides

    DEFF Research Database (Denmark)

    Matzen, René; Jensen, Jakob Søndergaard; Sigmund, Ole

    2011-01-01

    A pulse-delaying optimization scheme based on topology optimization for transient response of photonic crystal structures (PhCs) is formulated to obtain slow-light devices. The optimization process is started from a qualified W1 PhC waveguide design with group index ng≈40 obtained from a simple E...

  6. 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.

  7. 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.

  8. 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.; Ten Kate, M. K.; Lijfering, W. M.; Veeger, N. J. G. M.; Mulder, A. B.; Kluin-Nelemans, H. C.; van der Meer, J.

    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

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. Interaction of mono- and dianions with cyanase: evidence for apparent half-site binding.

    Science.gov (United States)

    Anderson, P M; Johnson, W V; Endrizzi, J A; Little, R M; Korte, J J

    1987-06-30

    Cyanase is an inducible enzyme in Escherichia coli that catalyzes bicarbonate-dependent hydrolysis of cyanate. The dianions oxalate, oxalacetate, and malonate are slow-binding inhibitors of cyanase, and some monoanions such as azide and chloride also inhibit cyanase activity [Anderson, P. M., & Little, R. M. (1986) Biochemistry 25, 1621-1626]. The purpose of this study was to investigate the interaction of selected dianions and monoanions by kinetic and equilibrium dialysis binding studies in an effort to obtain information about the active site and catalytic mechanism. Measurement of the effectiveness of 30 different dianions as inhibitors of cyanase showed a significant degree of structural and/or isomeric specificity and considerable variation with respect to the slow-binding nature of the inhibition. Oxalate and oxalacetate both show extreme slow-binding inhibition at very low concentrations. Kinetic studies of the rate of inhibition of cyanase by oxalate showed that the reaction is pseudo first order with respect to oxalate concentration and the results are consistent with a pathway in which oxalate forms a complex with the enzyme in a rapid initial reversible step followed by a slow isomerization step leading to a complex with a very low dissociation constant. The rate of inhibition is significantly reduced by the presence of relatively low concentrations of either azide (analogue of cyanate) or bicarbonate. Equilibrium dialysis binding studies showed that the stoichiometry of binding at saturation for oxalate, malonate, chloride, and bicarbonate is about 0.5 mol of ligand bound/mol of subunit for each compound.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. 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...

  16. 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…

  17. 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.

  18. Megalin binds and mediates cellular internalization of folate binding protein

    DEFF Research Database (Denmark)

    Birn, Henrik; Zhai, Xiaoyue; Holm, Jan;

    2005-01-01

    Folate is an essential vitamin involved in a number of biological processes. High affinity folate binding proteins (FBPs) exist both as glycosylphosphatidylinositol-linked, membrane associated folate binding proteins and as soluble FBPs in plasma and some secretory fluids such as milk, saliva...... to bind and mediate cellular uptake of FBP. Surface plasmon resonance analysis shows binding of bovine and human milk FBP to immobilized megalin, but not to low density lipoprotein receptor related protein. Binding of (125)I-labeled folate binding protein (FBP) to sections of kidney proximal tubule, known...... to express high levels of megalin, is inhibitable by excess unlabeled FBP and by receptor associated protein, a known inhibitor of binding to megalin. Immortalized rat yolk sac cells, representing an established model for studying megalin-mediated uptake, reveal (125)I-labeled FBP uptake which is inhibited...

  19. Cooperativity in highly aggregated enzyme systems. A slow transition model for the pyruvate dehydrogenase complex from Escherichia coli.

    Science.gov (United States)

    Bisswanger, H

    1984-02-25

    Three models are compared describing cooperative phenomena in enzymatic reactions in order to explain sigmoidal saturation curves found with the pyruvate dehydrogenase complex from Escherichia coli: the concerted model, the sequential model, and the slow transition model. Both the concerted and the sequential model were considered especially with regard to the increasing number of identical interaction subunits (protomers) in order to get close to the situation found with the pyruvate dehydrogenase complex which consists of 24 protomers. Applying the sequential model to a great number of protomers results in a weak increase of the Hill coefficient, while, in addition to this effect, the concerted model drastically shifts the sigmoidal range of the saturation function to very low ligand concentrations. Such shift is seen with saturation curves of pyruvate and thiamine disphosphate with the pyruvate dehydrogenase complex and a good fit with theoretical curves derived from the concerted model is obtained. However, subcomplexes with a reduced number of protomers exhibited no change in saturation behavior, thus providing evidence against concerted conformational changes of all subunits of the enzyme complex. A scheme for the initial reaction of the pyruvate dehydrogenase complex based on slow transitions is presented and a rate equation has been derived. Ordered binding of thiamine diphosphate and pyruvate and a ligand-induced slow transition between a less active and a fully active enzyme form has been assumed. The curves simulated with this model are in agreement with all essential kinetic data, which are observed with the pyruvate dehydrogenase complex: the atypical shape of the saturation curves of pyruvate and thiamine diphosphate, the respective Hill coefficients and Michaelis constants, the hyperbolic binding behavior of thiamine diphosphate, and the inhibition pattern found for acetyl coenzyme A. PMID:6365912

  20. Carboplatin binding to histidine

    Energy Technology Data Exchange (ETDEWEB)

    Tanley, Simon W. M. [University of Manchester, Brunswick Street, Manchester M13 9PL (United Kingdom); Diederichs, Kay [University of Konstanz, D-78457 Konstanz (Germany); Kroon-Batenburg, Loes M. J. [Utrecht University, Padualaan 8, 3584 CH Utrecht (Netherlands); Levy, Colin [University of Manchester, 131 Princess Street, Manchester M1 7DN (United Kingdom); Schreurs, Antoine M. M. [Utrecht University, Padualaan 8, 3584 CH Utrecht (Netherlands); Helliwell, John R., E-mail: john.helliwell@manchester.ac.uk [University of Manchester, Brunswick Street, Manchester M13 9PL (United Kingdom)

    2014-08-29

    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.

  1. Phenomenology of non-volcanic deep tremor, slow slip and the third slow earthquake in southwest Japan subduction zone

    Science.gov (United States)

    Obara, K.; Ito, Y.; Sekine, S.; Hirose, H.; Shiomi, K.

    2006-12-01

    Coupling phenomena of the non-volcanic low-frequency tremor and short-term slow slip event reflect the subduction process at the transition zone of deeper plate interface. In southwest Japan, non-volcanic tremors are distributed in some clusters along the 30km depth contour line of the upper boundary of the subducting Philippine Sea plate [Obara, 2002]. Peak of tremor activity recurs with regular intervals accompanying to short- term slow slip event lasting for a several days [Obara, et al., 2004]. In western Shikoku, the episodic tremor and slow slip have been clearly detected every six months. On the other hand, in central and eastern Shikoku, the tremor occurs with a few months interval. This suggests that the periodic stick-slip behavior has a spatial variation along the same slab. The regularity of recurrence interval is sometimes distorted by other seismic phenomena. In western Shikoku, the episodic tremor and slip occurred in winter and summer during two years of 2001 and 2002. However, during and after the period of the long-term slow slip event on the latter half of 2003 in this area, the recurrence interval was shortened to three months. Then, the half-year interval returned again since 2005. Northern Kii and Tokai areas, located on both sides of the Ise Bay, central part of Japan, are active tremor and slip source areas with the recurrence interval of six months. In December 2004 and July 2005, the episodic tremor and slip occurred in both areas independently with time gap of a few weeks. On the other hand, in January 2006, the tremor and slow slip began from the central part of Kii peninsula and gradually migrated to northeast. The activity at last went across the Ise Bay and advanced through the Tokai area. This continuous activity extending for 200km is the first accident since the tremor monitoring has started from 2001. Beneath the Ise Bay area, the configuration of the subducting Philippine Sea plate has a small ridge structure estimated from the

  2. ON THE SOURCE OF PROPAGATING SLOW MAGNETOACOUSTIC WAVES IN SUNSPOTS

    Energy Technology Data Exchange (ETDEWEB)

    Prasad, S. Krishna; Jess, D. B. [Astrophysics Research Centre, School of Mathematics and Physics, Queen' s University Belfast, Belfast BT7 1NN (United Kingdom); Khomenko, Elena, E-mail: krishna.prasad@qub.ac.uk [Instituto de Astrofísica de Canarias, E-38205 La Laguna, Tenerife (Spain)

    2015-10-10

    Recent high-resolution observations of sunspot oscillations using simultaneously operated ground- and space-based telescopes reveal the intrinsic connection between different layers of the solar atmosphere. However, it is not clear whether these oscillations are externally driven or generated in situ. We address this question by using observations of propagating slow magnetoacoustic waves along a coronal fan loop system. In addition to the generally observed decreases in oscillation amplitudes with distance, the observed wave amplitudes are also found to be modulated with time, with similar variations observed throughout the propagation path of the wave train. Employing multi-wavelength and multi-instrument data, we study the amplitude variations with time as the waves propagate through different layers of the solar atmosphere. By comparing the amplitude modulation period in different layers, we find that slow magnetoacoustic waves observed in sunspots are externally driven by photospheric p-modes, which propagate upward into the corona before becoming dissipated.

  3. Ionization of Atoms by Slow Heavy Particles, Including Dark Matter.

    Science.gov (United States)

    Roberts, B M; Flambaum, V V; Gribakin, G F

    2016-01-15

    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 9σ 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, cusplike behavior 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, enhancing the differential cross section by up to 1000 times.

  4. Towards An Ideal Slow Cookoff Model For PBXN-109

    Energy Technology Data Exchange (ETDEWEB)

    Wardell, J F; Maienschein, J L; Yoh, J J; Nichols, A L; McClelland, M A

    2003-11-21

    We present an overview of computational techniques for simulating the thermal cookoff of high explosives using a multi-physics hydrodynamics code, ALE3D. Recent improvements to the code have aided our computational capability in modeling the response of energetic materials systems exposed to extreme thermal environments, such as fires. We consider an idealized model process for a confined explosive involving the transition from slow heating to rapid deflagration in which the time scale changes from days to hundreds of microseconds. The heating stage involves thermal expansion and decomposition according to an Arrhenius kinetics model while a pressure-dependent burn model is employed during the explosive phase. We describe and demonstrate the numerical strategies employed to make the transition from slow to fast dynamics. In addition, we investigate the sensitivity of wall expansion rates to numerical strategies and parameters. Results from a one-dimensional model show increased violence when the gap between the explosive and steel vessel is removed.

  5. Simultaneous slow and fast light involving Faraday effect

    CERN Document Server

    Macke, Bruno

    2016-01-01

    We theoretically study the linear transmission of linearly polarized light pulses in an ensemble of cold atoms submitted to a static magnetic field parallel to the direction of propagation. The carrier frequency of the incident pulses coincides with a resonance frequency of the atoms in absence of magnetic field and the light transmitted in presence of magnetic field is examined in the polarizations parallel and perpendicular to that of the incident pulses. We give explicit analytic expressions of the transfer functions of the system for both polarizations. We demonstrate that slow light can be observed in a polarization whereas fast light is simultaneously observed in the perpendicular polarization. Moreover we point out that, due to the polarization post-selection, the system is not necessarily minimum-phase-shift. Slow light can then be obtained in situations where an irrelevant application of the Kramers-Kronig relations leads to expect fast light. When the incident light is step-modulated, we finally sho...

  6. Model independent analysis on the slowing down of cosmic acceleration

    CERN Document Server

    Zhang, Ming-Jian

    2016-01-01

    Possible slowing down of cosmic acceleration has attracted more and more attention. However, most analysis in previous work were commonly imposed in some parametrization models. In the present paper, we investigate this subject using the the Gaussian processes (GP), providing a model-independent analysis. We carry out the reconstruction by abundant data including luminosity distance from Union2, Union2.1 compilation and gamma-ray burst, and Hubble parameter from cosmic chronometer and baryon acoustic oscillation peaks. The GP reconstructions suggest that no slowing down of cosmic acceleration is approved within 95\\% C.L. from current observational data. We also test the influence of spatial curvature and Hubble constant, finding that spatial curvature does not present significant impact on the reconstructions. However, Hubble constant strongly influence the reconstructions especially at low redshift. In order to reveal the reason of inconsistence between our reconstruction and previous parametrization constra...

  7. Formation of slow shock pairs associated with coronal mass ejections

    Science.gov (United States)

    Whang, Y. V.

    1990-01-01

    The formation of a forward-reverse slow shock pair in the solar corona is presently simulated by an MHD model that uses the Rankine-Hugoniot solution to calculate the flow-property jumps at all shock crossings. The shocks divide the solution-domain into several continuous flow regions whose respective governing characteristics are solved by the method of characteristics. The plasma impact compresses the plasma near the front of the coronal mass ejection (CME); as the CME-associated slow shock pair moves outwards in interplanetary space, it evolves into a pair of fast shocks. All three phenomena are eventually manifested in interplanetary space as a magnetic cloud accompanied by a fast shock pair, with a forward shock preceding the cloud and a reverse shock appearing either within or behind the cloud.

  8. A device used in pulsed slow positron beam's stretching

    International Nuclear Information System (INIS)

    A slow positron beam's stretching device has been designed and constructed on Beijing Slow Positron Beam, which based on a 1.3 GeV linac. Positron was storage and stretching use Penning-Trap technique. Measurements show that the positron storage time strongly depends on the vacuum level in Penning Trap tube. Two modes was used to release the positrons from storage part, lowering VC while VB kept constant and rising VB while VC kept constant. This technique makes the pulsed positron beam to a quasi-continuous beam. The energy spread of positrons depend on in release mode. In the latter mode, the authors observe that the energy spread was reduced to a value less than 1.0 eV. The time profile in user-defined waveform is more uniform. It is beneficial to reduce the probability of amplifier pileup especially in the case of measurement with high counting rate. (authors)

  9. The phase transition to slow-roll eternal inflation

    International Nuclear Information System (INIS)

    For slow-roll inflation we study the phase transition to the eternal regime. Starting from a finite inflationary volume, we consider the volume of the universe at reheating as order parameter. We show that there exists a critical value for the classical inflation speed, φ-dot2/H4 = 3/(2 π2), where the probability distribution for the reheating volume undergoes a sharp transition. In particular, for sub-critical inflation speeds all distribution moments become infinite. We show that at the same transition point the system develops a non-vanishing probability of having a strictly infinite reheating volume, while retaining a finite probability for finite values. Our analysis represents the exact quantum treatment of the system at lowest order in the slow-roll parameters and H2/MPl2. (author)

  10. Slow waves in locally resonant metamaterials line defect waveguides

    CERN Document Server

    Kaina, Nadège; Bourlier, Yoan; Fink, Mathias; Berthelot, Thomas; Lerosey, Geoffroy

    2016-01-01

    The ability of electromagnetic waves to interact with matter governs many fascinating effects involved in fundamental and applied, quantum and classical physics. It is necessary to enhance these otherwise naturally weak effects by increasing the probability of wave/matter interactions, either through field confinement or slowing down of waves. This is commonly achieved with structured materials such as photonic crystal waveguides or coupled resonator optical waveguides. Yet their minimum structural scale is limited to the order of the wavelength which not only forbids ultra-small confinement but also severely limits their performance for slowing down waves. Here we show that line defect waveguides in locally resonant metamaterials can outperform these proposals due to their deep subwavelength scale. We experimentally demonstrate our approach in the microwave domain using 3D printed resonant wire metamaterials, achieving group indices ng as high as 227 over relatively wide frequency bands. Those results corres...

  11. The resonance escape probability during the neutron slowing down

    International Nuclear Information System (INIS)

    Three different methods were used to calculate the neutron resonance escape probability during neutron slowing down in homogeneous media : two Monte Carlo simulations and a determinist method. The first simulation is based on a natural process intervening in neutron transport, the second is a nonanalog simulation while the determinist method is based on an iterative solution of the neutron slowing down equation. The results are in a good agreement for the three methods . The second simulation was found to be more efficient than the first one for high dilutions . In fact we have attained a better figure of merite ( FOM = 1/ (sigma sup 2 ) T) by the second simulation than by the first one . 2 figs. ; 2 refs ( author )

  12. Investigation and realization of a slow-positron beam

    International Nuclear Information System (INIS)

    This research thesis first proposes a presentation of the GBAR project (Gravitational Behaviour of Anti-hydrogen at Rest) within which this research took place, and which aims at performing the first direct test of the Weak Equivalence Principle on anti-matter by studying the free fall of anti-hydrogen atoms in the Earth gravitational field. The author presents different aspects of this project: scientific objective, experiment principle and structure, detailed structure (positron beam, positron trap, positron/positronium conversion, anti-proton beam, trapping, slowing down and neutralisation of anti-hydrogen ions). The author then reports the design of the positron beam: study of source technology, studies related to the fast positron source, design of the low positron line (approach, functions, simulations, technology). The two last chapters report the construction and the characterization of the slow-positron line

  13. Slow light and pulse propagation in semiconductor waveguides

    DEFF Research Database (Denmark)

    Hansen, Per Lunnemann

    This thesis concerns the propagation of optical pulses in semiconductor waveguide structures with particular focus on methods for achieving slow light or signal delays. Experimental pulse propagation measurements of pulses with a duration of 180 fs, transmitted through quantum well based waveguide...... structures, are presented. Simultaneous measurements of the pulse transmission and delay are measured as a function of input pulse energy for various applied electrical potentials. Electrically controlled pulse delay and advancement are demonstrated and compared with a theoretical model. The limits...... of the model as well as the underlying physical mechanisms are analysed and discussed. A method to achieve slow light by electromagnetically induced transparency (EIT) in an inhomogeneously broadened quantum dot medium is proposed. The basic principles of EIT are assessed and the main dissimilarities between...

  14. Slow dynamics of the contact process on complex networks

    Directory of Open Access Journals (Sweden)

    Ódor Géza

    2013-03-01

    Full Text Available The Contact Process has been studied on complex networks exhibiting different kinds of quenched disorder. Numerical evidence is found for Griffiths phases and other rare region effects, in Erdős Rényi networks, leading rather generically to anomalously slow (algebraic, logarithmic,… relaxation. More surprisingly, it turns out that Griffiths phases can also emerge in the absence of quenched disorder, as a consequence of sole topological heterogeneity in networks with finite topological dimension. In case of scalefree networks, exhibiting infinite topological dimension, slow dynamics can be observed on tree-like structures and a superimposed weight pattern. In the infinite size limit the correlated subspaces of vertices seem to cause a smeared phase transition. These results have a broad spectrum of implications for propagation phenomena and other dynamical process on networks and are relevant for the analysis of both models and empirical data.

  15. Slow Magnetoacoustic Oscillations in the Microwave Emission of Solar Flares

    CERN Document Server

    Kim, Sujin; Shibasaki, K

    2013-01-01

    Analysis of the microwave data, obtained in the 17 GHz channel of the Nobeyama Radioheliograph during the M1.6 flare on 4th Nov 2010, revealed the presence of 11.8-min oscillations of the emitting plasma density. The oscilla- tions decayed with the characteristic time of about 25-min. These oscillations are also well-seen in the variation of EUV emission intensity measured in the 335 A channel of SDO/AIA. The observed properties of the oscillations are consistent with the properties of so-called SUMER oscillations, observed in the EUV and soft X-ray bands usually as a periodic Doppler shift. The accepted interpretation of SUMER oscillations is a standing slow magnetoacoustic wave. Our analysis presents the first direct observation of the slow magnetoacoustic oscillations in the microwave emission of a solar flare.

  16. Viscous Moment, Mechanism of Slow Slip, and Subduction Megathrust Viscosity

    Science.gov (United States)

    Fagereng, A.

    2015-12-01

    Slow slip events (SSEs) represent transient slip velocities slower than earthquakes but faster than steady, average plate motion. SSEs repeating at the same location have characteristic slip magnitude and duration. Contrary to earthquakes, however, average slip relates to neither duration nor area. Variations in duration, slip, and slip rate can instead be tied to variations in effective viscosity, calculated from a viscous definition of moment. In this paradigm, the observation that deep slow slip events are slower and longer, implies a higher effective viscosity than in shallower, colder SSEs. Observed variations in effective viscosity and slip rate can be interpreted in terms of differences in driving stress and shear zone width, and likely arise in anastomosing shear zones containing a heterogeneous mixture of materials.

  17. Nonlinear Processes in Coronal Heating and Slow Solar Wind Acceleration

    CERN Document Server

    Rappazzo, A F

    2010-01-01

    This work consists of two parts: the first devoted to the study of the heating of the magnetically confined Solar Corona, and the second to the acceleration of the Slow Solar Wind. Direct 3D reduced MHD simulations are presented. They model the heating of coronal loops in the solar atmosphere via the tangling of coronal field lines by photospheric footpoints motions within the framework of the "Parker scenario". We have derived scalings of physical quantities with loop length, and the ratio of photospheric to coronal Alfven velocities. The development of a turbulent dynamics makes the dissipation rate independent of the Reynolds number. The dynamics in physical space are desribed by weak turbulence, which develops when an MHD system is embedded in a strong axial magnetic field. The slow wind originates in and around the coronal streamer belt. The LASCO instrument onboard the SOHO spacecraft has observed plasma density enhancements forming beyond the cusp of a helmet streamer. Previous theoretical models for t...

  18. Can slow roll inflation induce relevant helical magnetic fields?

    CERN Document Server

    Durrer, Ruth; Jain, Rajeev Kumar

    2010-01-01

    We study the generation of helical magnetic fields during inflation induced by an axial coupling of the electromagnetic field to the inflaton. During slow roll inflation, we find that such a coupling always leads to a blue spectrum with $B^2 \\propto k$. We also show that a short deviation from slow roll does not result in strong modifications to the shape of the spectrum. The magnetic energy density at the end of inflation is too small to back-react on the background dynamics of the inflaton. We calculate the evolution of the correlation length and the field amplitude during the inverse cascade and viscous damping of the helical magnetic field in the radiation era after inflation. The final magnetic fields turn out to be far too weak to provide the seeds for the observed fields in galaxies and clusters.

  19. Elements of slow-neutron scattering basics, techniques, and applications

    CERN Document Server

    Carpenter, J M

    2015-01-01

    Providing a comprehensive and up-to-date introduction to the theory and applications of slow-neutron scattering, this detailed book equips readers with the fundamental principles of neutron studies, including the background and evolving development of neutron sources, facility design, neutron scattering instrumentation and techniques, and applications in materials phenomena. Drawing on the authors' extensive experience in this field, this text explores the implications of slow-neutron research in greater depth and breadth than ever before in an accessible yet rigorous manner suitable for both students and researchers in the fields of physics, biology, and materials engineering. Through pedagogical examples and in-depth discussion, readers will be able to grasp the full scope of the field of neutron scattering, from theoretical background through to practical, scientific applications.

  20. Characterizing micro-macro transitions with slow light

    CERN Document Server

    Zhou, Zhifan; Glasser, Ryan T; Qin, Zhongzhong; Fang, Yami; Jing, Jietai; Zhang, Weiping

    2016-01-01

    The transition between the microscopic to the macroscopic world is of broad fundamental and technological significance. Optical parametric amplifiers allow for amplifying single photons to the macroscopic level, but the underlying temporal dynamics are still not well understood. Slow light, in which the group velocity is delayed via quantum interference, is an effective tool to interrogate the temporal dynamics of light-matter interactions. Here, we demonstrate a scheme to characterize micro-macro transitions with slow light based on a four-wave mixing linear amplification process in a hot rubidium vapour. The scheme exhibits strong dispersion which is sensitive to the input's change at the single-photon level, resulting in a nonlinear decay of the micro-macro transition time with the increased microscopic input. The present system is suitable for the study of the relevant time scale of quantum-to-classical transitions and the potential impact from fundamental effects such as gravity, as indicated by recent p...