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Sample records for binding protein-c slow

  1. Myosin Binding Protein-C Slow: An Intricate Subfamily of Proteins

    Directory of Open Access Journals (Sweden)

    Maegen A. Ackermann

    2010-01-01

    Full Text Available Myosin binding protein C (MyBP-C consists of a family of thick filament associated proteins. Three isoforms of MyBP-C exist in striated muscles: cardiac, slow skeletal, and fast skeletal. To date, most studies have focused on the cardiac form, due to its direct involvement in the development of hypertrophic cardiomyopathy. Here we focus on the slow skeletal form, discuss past and current literature, and present evidence to support that: (i MyBP-C slow comprises a subfamily of four proteins, resulting from complex alternative shuffling of the single MyBP-C slow gene, (ii the four MyBP-C slow isoforms are expressed in variable amounts in different skeletal muscles, (iii at least one MyBP-C slow isoform is preferentially found at the periphery of M-bands and (iv the MyBP-C slow subfamily may play important roles in the assembly and stabilization of sarcomeric M- and A-bands and regulate the contractile properties of the actomyosin filaments.

  2. Myosin binding protein-C slow: a multifaceted family of proteins with a complex expression profile in fast and slow twitch skeletal muscles.

    Science.gov (United States)

    Ackermann, Maegen A; Kontrogianni-Konstantopoulos, Aikaterini

    2013-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Regulation of jaw-specific isoforms of myosin-binding protein-C and tropomyosin in regenerating cat temporalis muscle innervated by limb fast and slow motor nerves.

    Science.gov (United States)

    Kang, Lucia H D; Hoh, Joseph F Y

    2010-11-01

    Cat jaw-closing muscles are a distinct muscle allotype characterized by the expression of masticatory-specific myofibrillar proteins. Transplantation studies showed that expression of masticatory myosin heavy chain (m-MyHC) is promoted by fast motor nerves, but suppressed by slow motor nerves. We investigated whether masticatory myosin-binding protein-C (m-MBP-C) and masticatory tropomyosin (m-Tm) are similarly regulated. Temporalis muscle strips were transplanted into limb muscle beds to allow innervation by fast or slow muscle nerve during regeneration. Regenerated muscles were examined postoperatively up to 168 days by peroxidase IHC using monoclonal antibodies to m-MyHC, m-MBP-C, and m-Tm. Regenerates in both muscle beds expressed fetal and slow MyHCs, m-MyHC, m-MBP-C, and m-Tm during the first 4 weeks. Longer-term regenerates innervated by fast nerve suppressed fetal and slow MyHCs, retaining m-MyHC, m-MBP-C, and m-Tm, whereas fibers innervated by slow nerve suppressed fetal MyHCs and the three masticatory-specific proteins, induced slow MyHC, and showed immunohistochemical characteristics of jaw-slow fibers. We concluded that expression of m-MBP-C and m-Tm is coregulated by m-MyHC and that neural impulses to limb slow muscle are capable of suppressing masticatory-specific proteins and to channel gene expression along the jaw-slow phenotype unique to jaw-closing muscle.

  5. Zinc ions bind to and inhibit activated protein C

    DEFF Research Database (Denmark)

    Zhu, Tianqing; Ubhayasekera, Wimal; Nickolaus, Noëlle

    2010-01-01

    Zn2+ ions were found to efficiently inhibit activated protein C (APC), suggesting a potential regulatory function for such inhibition. APC activity assays employing a chromogenic peptide substrate demonstrated that the inhibition was reversible and the apparent K I was 13 +/- 2 microM. k cat was ...

  6. 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...

  7. Dilated cardiomyopathy in homozygous myosin-binding protein-C mutant mice

    OpenAIRE

    1999-01-01

    To elucidate the role of cardiac myosin-binding protein-C (MyBP-C) in myocardial structure and function, we have produced mice expressing altered forms of this sarcomere protein. The engineered mutations encode truncated forms of MyBP-C in which the cardiac myosin heavy chain-binding and titin-binding domain has been replaced with novel amino acid residues. Analogous heterozygous defects in humans cause hypertrophic cardiomyopathy. Mice that are homozygous for the mutated MyBP-C alleles expre...

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

    Science.gov (United States)

    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.

  9. 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.

  10. 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.

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

    Science.gov (United States)

    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.

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

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

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

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

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

    2016-03-22

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    OBJECTIVES: A missense mutation (A31P) in the cardiac myosin binding protein C gene has been associated with hypertrophic cardiomyopathy (HCM) in Maine Coon cats. The aim of this study was to investigate the effect of A31P on development of HCM, myocardial diastolic dysfunction detected by color ...

  20. 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...

  1. Differential roles of regulatory light chain and myosin binding protein-C phosphorylations in the modulation of cardiac force development

    Energy Technology Data Exchange (ETDEWEB)

    Colson, Brett A.; Locher, Matthew R.; Bekyarova, Tanya; Patel, Jitandrakumar R.; Fitzsimons, Daniel P.; Irving, Thomas C.; Moss, Richard L. (IIT); (UW-MED)

    2010-05-25

    Phosphorylation of myosin regulatory light chain (RLC) by myosin light chain kinase (MLCK) and myosin binding protein-C (cMyBP-C) by protein kinase A (PKA) independently accelerate the kinetics of force development in ventricular myocardium. However, while MLCK treatment has been shown to increase the Ca{sup 2+} sensitivity of force (pCa{sub 50}), PKA treatment has been shown to decrease pCa{sub 50}, presumably due to cardiac troponin I phosphorylation. Further, MLCK treatment increases Ca{sup 2+}-independent force and maximum Ca{sup 2+}-activated force, whereas PKA treatment has no effect on either force. To investigate the structural basis underlying the kinase-specific differential effects on steady-state force, we used synchrotron low-angle X-ray diffraction to compare equatorial intensity ratios (I{sub 1,1}/I{sub 1,0}) to assess the proximity of myosin cross-bridge mass relative to actin and to compare lattice spacings (d{sub 1,0}) to assess the inter-thick filament spacing in skinned myocardium following treatment with either MLCK or PKA. As we showed previously, PKA phosphorylation of cMyBP-C increases I{sub 1,1}/I{sub 1,0} and, as hypothesized, treatment with MLCK also increased I{sub 1,1}/I{sub 1,0}, which can explain the accelerated rates of force development during activation. Importantly, interfilament spacing was reduced by {approx}2 nm ({Delta} 3.5%) with MLCK treatment, but did not change with PKA treatment. Thus, RLC or cMyBP-C phosphorylation increases the proximity of cross-bridges to actin, but only RLC phosphorylation affects lattice spacing, which suggests that RLC and cMyBP-C modulate the kinetics of force development by similar structural mechanisms; however, the effect of RLC phosphorylation to increase the Ca{sup 2+} sensitivity of force is mediated by a distinct mechanism, most probably involving changes in interfilament spacing.

  2. The development and application of a high-sensitivity immunoassay for cardiac myosin–binding protein C

    Science.gov (United States)

    Marjot, Jack; Liebetrau, Christoph; Goodson, Robert J.; Kaier, Thomas; Weber, Ekkehard; Heseltine, Peter; Marber, Michael S.

    2016-01-01

    Cardiac troponins (cTns) are released and cleared slowly after myocardial injury. Cardiac myosin–binding protein C (cMyC) is a similar cardiac-restricted protein that has more rapid release and clearance kinetics. Direct comparisons are hampered by the lack of an assay for cMyC that matches the sensitivity of the contemporary assays for cTnI and cTnT. Using a novel pair of monoclonal antibodies, we generated a sensitive assay for MyC on the Erenna platform (Singulex) and compared serum concentrations with those of cTnI (Abbott) and cTnT (Roche) in stable ambulatory cardiac patients without evidence of acute cardiac injury or significant coronary artery stenoses. The assay for cMyC had a lower limit of detection of 0.4 ng/L, a lower limit of quantification (LLoQ) of 1.2 ng/L (LLoQ at 20% coefficient of variation [CV]) and reasonable recovery (107.1 ± 3.7%; mean ± standard deviation), dilutional linearity (101.0 ± 7.7%), and intraseries precision (CV, 11 ± 3%) and interseries precision (CV, 13 ± 3%). In 360 stable patients, cMyC was quantifiable in 359 patients and compared with cTnT and cTnI measured using contemporary high-sensitivity assays. cMyC concentration (median, 12.2 ng/L; interquartile range [IQR], 7.9–21.2 ng/L) was linearly correlated with those for cTnT (median, <3.0 ng/L; IQR, <3.0–4.9 ng/L; R = 0.56, P < 0.01) and cTnI (median, 2.10 ng/L; IQR, 1.3–4.2 ng/L; R = 0.77, P < 0.01) and showed similar dependencies on age, renal function, and left ventricular function. We have developed a high-sensitivity assay for cMyC. Concentrations of cMyC in clinically stable patients are highly correlated with those of cTnT and cTnI. This high correlation may enable ratiometric comparisons between biomarkers to distinguish clinical instability. PMID:26713894

  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

    Directory of Open Access Journals (Sweden)

    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. 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.

  7. 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.

  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. Complexes containing activating transcription factor (ATF)/cAMP-responsive-element-binding protein (CREB) interact with the CCAAT/enhancer-binding protein (C/EBP)-ATF composite site to regulate Gadd153 expression during the stress response.

    Science.gov (United States)

    Fawcett, T W; Martindale, J L; Guyton, K Z; Hai, T; Holbrook, N J

    1999-01-01

    Gadd153, also known as chop, encodes a member of the CCAAT/enhancer-binding protein (C/EBP) transcription factor family and is transcriptionally activated by cellular stress signals. We recently demonstrated that arsenite treatment of rat pheochromocytoma PC12 cells results in the biphasic induction of Gadd153 mRNA expression, controlled in part through binding of C/EBPbeta and two uncharacterized protein complexes to the C/EBP-ATF (activating transcription factor) composite site in the Gadd153 promoter. In this report, we identified components of these additional complexes as two ATF/CREB (cAMP-responsive-element-binding protein) transcription factors having differential binding activities dependent upon the time of arsenite exposure. During arsenite treatment of PC12 cells, we observed enhanced binding of ATF4 to the C/EBP-ATF site at 2 h as Gadd153 mRNA levels increased, and enhanced binding of ATF3 complexes at 6 h as Gadd153 expression declined. We further demonstrated that ATF4 activates, while ATF3 represses, Gadd153 promoter activity through the C/EBP-ATF site. ATF3 also repressed ATF4-mediated transactivation and arsenite-induced activation of the Gadd153 promoter. Our results suggest that numerous members of the ATF/CREB family are involved in the cellular stress response, and that regulation of stress-induced biphasic Gadd153 expression in PC12 cells involves the ordered, sequential binding of multiple transcription factor complexes to the C/EBP-ATF composite site. PMID:10085237

  10. The expression of CCAAT/enhancer binding protein (C/EBP) in the human ovary in vivo: specific increase in C/EBPβ during epithelial tumour progression

    Science.gov (United States)

    Sundfeldt, K; Ivarsson, K; Carlsson, M; Enerbäck, S; Janson, P O; Brännström, M; Hedin, L

    1999-01-01

    The CCAAT/enhancer binding protein (C/EBP) family of transcription factors is involved in metabolism and differentiation of cells, especially in rodent liver cells and adipocytes. Their roles in vivo and in particular during pathophysiological conditions in humans are largely unknown. We have investigated the presence of C/EBPα, -β, -δ and -ζ in normal ovaries and in epithelial ovarian tumours of different stages. Immunohistochemical experiments demonstrated that C/EBPα and C/EBPβ were preferentially expressed in epithelial/tumour cells irrespective of stage or grade of the tumour. C/EBPβ was located in the nuclei of the cells, in contrast to C/EBPα, which was present only in the cytoplasm of these cells. The nuclear localization of C/EBPβ indicates an active role of this transcription factor in tumour cells, whereas the cytoplasmic distribution suggests a more passive function of C/EBPα. C/EBPδ and -ζ demonstrated a more diverse distribution with predominant localization to epithelial cells, but stromal distribution was also noted. The intracellular distribution was confined to both the nucleus and the cytoplasm for C/EBPδ and -ζ. Western blotting demonstrated that C/EBPα, -β, -δ and -ζ were present in a majority of the samples. The amount of C/EBPβ increased markedly with malignancy, i.e. with degree of dedifferentiation, while the other members of the C/EBP family displayed a more constant expression level. These results demonstrate an association between the expression of members of the C/EBP family and the formation of epithelial ovarian tumours, with C/EBPβ as a potential marker for these tumours. As C/EBPβ is known to be expressed during proliferation of cells in vitro, it may participate in the proliferative process of ovarian epithelial tumour cells in vivo and play a central role in tumour progression. © 1999 Cancer Research Campaign PMID:10098766

  11. Vaccinia virus protein C6 is a virulence factor that binds TBK-1 adaptor proteins and inhibits activation of IRF3 and IRF7.

    Directory of Open Access Journals (Sweden)

    Leonie Unterholzner

    2011-09-01

    Full Text Available Recognition of viruses by pattern recognition receptors (PRRs causes interferon-β (IFN-β induction, a key event in the anti-viral innate immune response, and also a target of viral immune evasion. Here the vaccinia virus (VACV protein C6 is identified as an inhibitor of PRR-induced IFN-β expression by a functional screen of select VACV open reading frames expressed individually in mammalian cells. C6 is a member of a family of Bcl-2-like poxvirus proteins, many of which have been shown to inhibit innate immune signalling pathways. PRRs activate both NF-κB and IFN regulatory factors (IRFs to activate the IFN-β promoter induction. Data presented here show that C6 inhibits IRF3 activation and translocation into the nucleus, but does not inhibit NF-κB activation. C6 inhibits IRF3 and IRF7 activation downstream of the kinases TANK binding kinase 1 (TBK1 and IκB kinase-ε (IKKε, which phosphorylate and activate these IRFs. However, C6 does not inhibit TBK1- and IKKε-independent IRF7 activation or the induction of promoters by constitutively active forms of IRF3 or IRF7, indicating that C6 acts at the level of the TBK1/IKKε complex. Consistent with this notion, C6 immunoprecipitated with the TBK1 complex scaffold proteins TANK, SINTBAD and NAP1. C6 is expressed early during infection and is present in both nucleus and cytoplasm. Mutant viruses in which the C6L gene is deleted, or mutated so that the C6 protein is not expressed, replicated normally in cell culture but were attenuated in two in vivo models of infection compared to wild type and revertant controls. Thus C6 contributes to VACV virulence and might do so via the inhibition of PRR-induced activation of IRF3 and IRF7.

  12. 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...

  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. Association between sex hormone-binding globulin levels and activated protein C resistance in explaining the risk of thrombosis in users of oral contraceptives containing different progestogens

    NARCIS (Netherlands)

    Vliet, van Huib A.A.M.; Frolich, Marijke; Christella, M.; Thomassen, L.G.D.; Doggen, Carine J.M.; Rosendaal, Frits R.; Rosing, Jan; Helmerhorst, Frans M.

    2005-01-01

    BACKGROUND: Epidemiological studies have shown that both the estrogen dose and progestogen type of oral contraceptives contribute to the increased risk of thrombosis in oral contraceptive users. Thrombin generation-based activated protein C (APC) sensitivity is a global test for the net prothromboti

  15. Lacosamide Inhibition of Nav1.7 Voltage-Gated Sodium Channels: Slow Binding to Fast-Inactivated States.

    Science.gov (United States)

    Jo, Sooyeon; Bean, Bruce P

    2017-04-01

    Lacosamide is an antiseizure agent that targets voltage-dependent sodium channels. Previous experiments have suggested that lacosamide is unusual in binding selectively to the slow-inactivated state of sodium channels, in contrast to drugs like carbamazepine and phenytoin, which bind tightly to fast-inactivated states. Using heterologously expressed human Nav1.7 sodium channels, we examined the state-dependent effects of lacosamide. Lacosamide induced a reversible shift in the voltage dependence of fast inactivation studied with 100-millisecond prepulses, suggesting binding to fast-inactivated states. Using steady holding potentials, lacosamide block was very weak at -120 mV (3% inhibition by 100 µM lacosamide) but greatly enhanced at -80 mV (43% inhibition by 100 µM lacosamide), where there is partial fast inactivation but little or no slow inactivation. During long depolarizations, lacosamide slowly (over seconds) put channels into states that recovered availability slowly (hundreds of milliseconds) at -120 mV. This resembles enhancement of slow inactivation, but the effect was much more pronounced at -40 mV, where fast inactivation is complete, but slow inactivation is not, than at 0 mV, where slow inactivation is maximal, more consistent with slow binding to fast-inactivated states than selective binding to slow-inactivated states. Furthermore, inhibition by lacosamide was greatly reduced by pretreatment with 300 µM lidocaine or 300 µM carbamazepine, suggesting that lacosamide, lidocaine, and carbamazepine all bind to the same site. The results suggest that lacosamide binds to fast-inactivated states in a manner similar to other antiseizure agents but with slower kinetics of binding and unbinding.

  16. 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.

  17. 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.

  18. 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.

  19. Changes of calcium binding proteins, c-Fos and COX in hippocampal formation and cerebellum of Niemann-Pick, type C mouse.

    Science.gov (United States)

    Byun, Kyunghee; Kim, Daesik; Bayarsaikhan, Enkhjaigal; Oh, Jeehyun; Kim, Jisun; Kwak, Grace; Jeong, Goo-Bo; Jo, Seung-Mook; Lee, Bonghee

    2013-09-01

    Niemann-Pick disease, type C (NPC) is an intractable disease that is accompanied by ataxia, dystonia, neurodegeneration, and dementia due to an NPC gene defect. Disruption of calcium homeostasis in neurons is important in patients with NPC. Thus, we used immunohistochemistry to assess the expression levels of calcium binding proteins (calbindin D28K, parvalbumin, and calretinin), c-Fos and cyclooxygenase-1,2 (COX-1,2) in the hippocampal formation and cerebellum of 4 and 8 week old NPC+/+, NPC+/-, and NPC-/- mice. General expression of these proteins decreased in the hippocampus and cerebellum of NPC-/- compared to that in both young and adult NPC+/+ or NPC+/- mice. Parvalbumin, COX-1,2 or c-Fos-immunoreactive neurons were widely detected in the CA1, CA3, and DG of the hippocampus, but the immunoreactivities were decreased sharply in all areas of hippocampus of NPC-/- compared to NPC+/+ and NPC+/- mice. Taken together, reduction of these proteins may be one of the strong phenotypes related to the neuronal degeneration in NPC-/- mice.

  20. 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.

  1. 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.

  2. 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.

  3. Cardiac Myosin Binding Protein C and Heart Failure with Preserved Ejection Fraction%心脏型肌球蛋白结合蛋白与射血分数保留的心力衰竭

    Institute of Scientific and Technical Information of China (English)

    张晨(综述); 常静(审校)

    2015-01-01

    Cardiac myosin binding protein C ( cMyBP-C) is not only the main part of cardiac thick filament,but a key regulator of car-diac contraction and diastolic function.Early studies have focused on gene variants in cMyBP-C with hypertrophic cardiomyopathy and the value of serum cMyBP-C in the diagnosis and prognosis evaluation of patients with acute myocardial infarction.With the rapid development of medical molecular biology and genomics, studies show that cMyBP-C phosphorylation is directly linked to signaling of diastolic function.More research has found that level of cMyBP-C phosphorylation is significantly decreased during the end-stage heart failure,indicating that cMyBP-C plays an important role in heart failure with preserved ejection fraction( HFpEF).We discusss the latest progress in the structure,function and regulation of cMyBP-C.We also attempt to shed some light on the relationship between the cMyBP-C and HFpEF.%心脏型肌球蛋白结合蛋白C不仅是心肌粗肌丝的主要组成部分,还是参与调节心肌细胞收缩舒张功能的重要物质之一。过去几十年的研究主要集中在心脏型肌球蛋白结合蛋白基因突变致肥厚型心肌病,以及血清心脏型肌球蛋白结合蛋白水平在急性心肌梗死患者的诊断、判断预后作用。近年来对心脏型肌球蛋白结合蛋白C通过磷酸化来调节心肌舒张功能方面有了新进展,而且,多个研究又发现难治性终末期心力衰竭患者的心脏型肌球蛋白结合蛋白磷酸化水平显著降低。这表明心脏型肌球蛋白结合蛋白可能对于舒张功能不全为特征的射血分数保留心力衰竭的发生发展很重要。在这个情况下,现综述总结心脏型肌球蛋白结合蛋白结构和功能的最新研究进展,并对心脏型肌球蛋白结合蛋白与射血分数保留心力衰竭的关系进行简要综述。

  4. Protein C Inhibitor-A Novel Antimicrobial Agent

    NARCIS (Netherlands)

    Malmström, E.; Mörgelin, M.; Malmsten, M.; Johansson, L.; Norrby-Teglund, A.; Shannon, O.; Schmidtchen, A.; Meijers, J.C.M.; Herwald, H.

    2009-01-01

    Protein C inhibitor (PCI) is a heparin-binding serine proteinase inhibitor belonging to the family of serpin proteins. Here we describe that PCI exerts broad antimicrobial activity against bacterial pathogens. This ability is mediated by the interaction of PCI with lipid membranes, which subsequentl

  5. Genetics Home Reference: protein C deficiency

    Science.gov (United States)

    ... Management Genetic Testing (1 link) Genetic Testing Registry: Thrombophilia, hereditary, due to protein C deficiency, autosomal dominant ... my area? Other Names for This Condition hereditary thrombophilia due to protein C deficiency PROC deficiency Related ...

  6. The research of myosin-binding protein C in duced autoimmune myositis model%肌球蛋白结合蛋白C诱导免疫性肌炎模型的研究

    Institute of Scientific and Technical Information of China (English)

    张寅丽; 周航; 彭清林; 尹利国; 舒晓明; 张思功; 卢昕; 赵千子; 王国春

    2015-01-01

    目的:采用重组人快型肌球蛋白结合蛋白C(MYBPC2)免疫小鼠获得自身免疫性肌炎模型。方法将MYBPC2与完全弗氏佐剂乳化后,以皮下多点注射免疫C57BL/6小鼠(0 d、7 d),同时腹腔注射百日咳毒素2μg。①探索不同剂量MYBPC2免疫小鼠,在不同时点肌肉病理变化情况。②以600μg/次免疫小鼠,在第21天检测其肌肉耐力,观察肌肉组织主要组织相容性复合体(MHC)-Ⅰ类分子以及炎症细胞浸润等病理变化。采用Mann-Whitney U检验进行统计分析。结果①随免疫剂量增加,肌肉损伤和炎症趋于严重,在21、28 d肌组织损伤最显著,模型组小鼠肌组织可见肌纤维变性、坏死和炎细胞浸润。②小鼠模型组肌肉耐力[(6.1±1.3) min]与对照组[(9.2±1.6) min]相比明显下降(U=2.00,P=0.017)。模型组肌纤维表面MHC-Ⅰ类分子阳性,肌纤维间及血管周围区域可见散在CD4+及CD8+T细胞、CD68+巨噬细胞浸润,CD20+B细胞主要分布于血管周围区域,肌纤维间少见。结论在国内首次采用MYBPC2成功诱导小鼠自身免疫性肌炎。 MYBPC2诱导的新型自身免疫性肌炎模型具备人类多发性肌炎相似的临床和肌肉病理特征,能够作为研究肌炎发病机制的新型工具。%Objective To establish a new murine model of experimental autoimmune myositis by immunizing with MYBPC2 protein. Methods The purified Myosin-binding protein C, fast type (MYBPC2) was emulsified with complete Freundˊs adjuvant, then C57BL/6 mice were immunized by multi-point subcutaneous injection (0, 7 days), and intraperitoneal injection of pertussis toxin 2 μg simultaneously. The pathological changes of mice with different immunizing dose at the preconceived time were ex-plored. Mean-while, mice were immunized with 600 μg each time, and the muscle endurance was tested on the 21th day. The expression of major histocompatibility complex (MHC) class

  7. 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...

  8. 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.

  9. Block of Human Cardiac Sodium Channels by Lacosamide: Evidence for Slow Drug Binding along the Activation Pathway

    OpenAIRE

    Wang, Ging Kuo; Wang, Sho-Ya

    2014-01-01

    Lacosamide is an anticonvulsant hypothesized to enhance slow inactivation of neuronal Na+ channels for its therapeutic action. Cardiac Na+ channels display less and incomplete slow inactivation, but their sensitivity toward lacosamide remains unknown. We therefore investigated the action of lacosamide in human cardiac Nav1.5 and Nav1.5-CW inactivation-deficient Na+ channels. Lacosamide showed little effect on hNav1.5 Na+ currents at 300 µM when cells were held at −140 mV. With 30-second condi...

  10. 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

  11. Fluoride inhibition of Klebsiella aerogenes urease: mechanistic implications of a pseudo-uncompetitive, slow-binding inhibitor.

    Science.gov (United States)

    Todd, M J; Hausinger, R P

    2000-05-09

    Klebsiella aerogenes urease uses a dinuclear nickel active site to catalyze the hydrolysis of urea. Here, we describe the steady-state and pre-steady-state kinetics of urease inhibition by fluoride. Urease is slowly inhibited by fluoride in both the presence and absence of substrate. Steady-state rate studies yield parallel double-reciprocal plots; however, we show that fluoride interaction with urease is not compatible with classical uncompetitive inhibition. Rather, we propose that fluoride binds to an enzyme state (E) that is in equilibrium with resting enzyme (E) and produced during catalysis. Fluoride binding rates are directly proportional to inhibitor concentration. Substrate reduces both the rate of fluoride binding to urease and the rate of fluoride dissociation from the complex, consistent with urea binding to E and E.F in addition to E. Fluoride inhibition is pH-dependent due to a protonation event linked to fluoride dissociation. Fluoride binding is pH-independent, suggesting that fluoride anion, not HF, is the actual inhibitor. We assess the kinetic results in terms of the known protein crystal structure and evaluate possible molecular interpretations for the structure of the E state, the site of fluoride binding, and the factors associated with fluoride release. Finally, we note that the apparent uncompetitive inhibition by fluoride as reported for several other metalloenzymes may need to be reinterpreted in terms of fluoride interaction with the corresponding E states.

  12. Characterization of the slow calcium channel binding sites for ( sup 3 H)SR 33557 in rat heart sarcolemmal membranes

    Energy Technology Data Exchange (ETDEWEB)

    Chatelain, P.; Beaufort, P.; Meysmans, L.; Clinet, M. (Sanofi-Labaz Research Centre, Brussels (Belgium))

    1991-01-01

    SR 33557 represents a new class of compounds (indolizine sulfone) that inhibit L-type Ca2+ channels. ({sup 3}H)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 ({sup 3}H)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 ({sup 3}H)SR 33557. However, dihydropyridines, phenylalkylamines, benzothiazepines, and diphenylbutylpiperidines were found to inhibit ({sup 3}H)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.

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

    Science.gov (United States)

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

    2016-05-01

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

  14. Block of human cardiac sodium channels by lacosamide: evidence for slow drug binding along the activation pathway.

    Science.gov (United States)

    Wang, Ging Kuo; Wang, Sho-Ya

    2014-05-01

    Lacosamide is an anticonvulsant hypothesized to enhance slow inactivation of neuronal Na(+) channels for its therapeutic action. Cardiac Na(+) channels display less and incomplete slow inactivation, but their sensitivity toward lacosamide remains unknown. We therefore investigated the action of lacosamide in human cardiac Nav1.5 and Nav1.5-CW inactivation-deficient Na(+) channels. Lacosamide showed little effect on hNav1.5 Na(+) currents at 300 µM when cells were held at -140 mV. With 30-second conditioning pulses from -90 to -50 mV; however, hNav1.5 Na(+) channels became sensitive to lacosamide with IC50 (50% inhibitory concentration) around 70-80 µM. Higher IC50 values were found at -110 and -30 mV. The development of lacosamide block at -70 mV was slow in wild-type Na(+) channels (τ; 8.04 ± 0.39 seconds, n = 8). This time constant was significantly accelerated in hNav1.5-CW inactivation-deficient counterparts. The recovery from lacosamide block at -70 mV for 10 seconds was relatively rapid in wild-type Na(+) channels (τ; 639 ± 90 milliseconds, n = 8). This recovery was accelerated further in hNav1.5-CW counterparts. Unexpectedly, lacosamide elicited a time-dependent block of persistent hNav1.5-CW Na(+) currents with an IC50 of 242 ± 19 µM (n = 5). Furthermore, both hNav1.5-CW/F1760K mutant and batrachotoxin-activated hNav1.5 Na(+) channels became completely lacosamide resistant, indicating that the lacosamide receptor overlaps receptors for local anesthetics and batrachotoxin. Our results together suggest that lacosamide targets the intermediate preopen and open states of hNav1.5 Na(+) channels. Lacosamide may thus track closely the conformational changes at the hNav1.5-F1760 region along the activation pathway.

  15. Liver myofibroblasts activate protein C and respond to activated protein C

    Institute of Scientific and Technical Information of China (English)

    Jennifer; Gillibert-Duplantier; Anne; Rullier; Véronique; Neaud; Walter; Kisiel; Jean; Rosenbaum

    2010-01-01

    AIM:To study the protein C activation system in human liver myofibroblasts,and the effects of activated protein C(APC)on these cells.METHODS:Human liver myofibroblasts were obtained by outgrowth.Expression of protease activated receptor 1(PAR-1),endothelial protein C receptor(EPCR) and thrombomodulin(TM)was analyzed by flow cytometry.Extracellular signal-regulated kinase(ERK)1/2 activation was assessed by Western blotting using anti-phospho-ERK antibodies.Collagen synthesis was studied with real-time revers...

  16. 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...

  17. 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.

  18. Slow Heartbeat

    Science.gov (United States)

    ... per minute. The heartbeat is controlled by an electrical system that signals the heart muscle to contract, or “squeeze,” pumping blood to the rest of the body. Bradycardia happens when the system slows or blocks ...

  19. Pesquisa de marcadores para os genes da cadeia pesada da beta-miosina cardíaca e da proteína C de ligação à miosina em familiares de pacientes com cardiomiopatia hipertrófica Research of markers for the genes of the heavy chain of cardiac beta-myosin and myosin binding protein C in relatives of patients with hypertrophic cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Adriana Paula Tirone

    2005-06-01

    Full Text Available OBJETIVO: Estudar os marcadores moleculares para os genes da cadeia pesada da beta-miosina cardíaca e da proteína-C de ligação à miosina em familiares de portadores de cardiomiopatia hipertrófica. MÉTODOS: Foram estudadas 12 famílias que realizaram anamnese, exame físico, eletrocardiograma, ecocardiograma e coleta de sangue para o estudo genético através da reação em cadeia da polimerasse. RESULTADOS: Dos 227 familiares 25% eram acometidos, sendo 51% do sexo masculino com idade média de 35±19 (2 a 95 anos. A análise genética mostrou ligação com o gene da b-miosina cardíaca em uma família e, em outra, ligação com o gene da proteína C de ligação à miosina. Em cinco famílias foram excluídas ligações com os dois genes; em duas, a ligação com o gene da proteína C de ligação à miosina, porém para o gene da b-miosina os resultados foram inconclusivos; em duas famílias os resultados foram inconclusivos para os dois genes e em uma foi excluída ligação para o gene da b-miosina mas ficou inconclusivo para o gene da proteína C de ligação à miosina. CONCLUSÃO: Em nosso meio, talvez predominem outros genes que não aqueles descritos na literatura, ou que existam outras diferenças genéticas relacionadas com a origem de nossa população e/ou fatores ambientais.OBJECTIVE: To study the molecular markers for the genes of the heavy chain of cardiac beta-myosin and the myosin binding protein C in relatives of carriers of hypertrophic cardiomyopathy. METHODS: Twelve families who had anamnesis, physical exam, electrocardiogram, echocardiogram and blood collection for the genetic study through the chain reaction of polymerase. RESULTS: From the 227 relatives, 25% were ill-taken, with 51% men, with an average age of 35±19 (2 to 95 years old. The genetic analysis showed a connection with the gene of the cardiac b-myosin in a family and, in another, a connection with the gene of the myosin-binding protein C. In five

  20. 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.

  1. 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.

  2. 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.

  3. 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.

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

    Science.gov (United States)

    Koshiar, Ruzica Livaja; Somajo, Sofia; Norström, Eva; Dahlbäck, Björn

    2014-01-01

    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-derived microparticle

  5. In situ hybridisation of a large repertoire of muscle-specific transcripts in fish larvae: the new superficial slow-twitch fibres exhibit characteristics of fast-twitch differentiation.

    Science.gov (United States)

    Chauvigné, F; Ralliere, C; Cauty, C; Rescan, P Y

    2006-01-01

    Much of the present information on muscle differentiation in fish concerns the early embryonic stages. To learn more about the maturation and the diversification of the fish myotomal fibres in later stages of ontogeny, we investigated, by means of in situ hybridisation, the developmental expression of a large repertoire of muscle-specific genes in trout larvae from hatching to yolk resorption. At hatching, transcripts for fast and slow muscle protein isoforms, namely myosins, tropomyosins, troponins and myosin binding protein C were present in the deep fast and the superficial slow areas of the myotome, respectively. During myotome expansion that follows hatching, the expression of fast isoforms became progressively confined to the borders of the fast muscle mass, whereas, in contrast, slow muscle isoform transcripts were uniformly expressed in all the slow fibres. Transcripts for several enzymes involved in oxidative metabolism such as citrate synthase, cytochrome oxidase component IV and succinate dehydrogenase, were present throughout the whole myotome of hatching embryos but in later stages became concentrated in slow fibre as well as in lateral fast fibres. Surprisingly, the slow fibres that are added externally to the single superficial layer of the embryonic (original) slow muscle fibres expressed not only slow twitch muscle isoforms but also, transiently, a subset of fast twitch muscle isoforms including MyLC1, MyLC3, MyHC and myosin binding protein C. Taken together these observations show that the growth of the myotome of the fish larvae is associated with complex patterns of muscular gene expression and demonstrate the unexpected presence of fast muscle isoform-expressing fibres in the most superficial part of the slow muscle.

  6. 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...

  7. Simulating the slow to fast switch in cytochrome c oxidase catalysis by introducing a loop flip near to the enzyme's cytochrome c (substrate) binding site.

    Science.gov (United States)

    Alleyne, Trevor; Ignacio, Diane N; Sampson, Valerie B; Ashe, Damian; Wilson, Michael

    2016-08-04

    The mitochondrial enzyme cytochrome c oxidase catalyses the reduction of molecular oxygen in the critical step of oxidative phosphorylation that links the oxidation of food consumed to ATP production in cells. The enzyme catalyses the reduction of oxygen at two vastly different rates that are thought to be linked to two different conformations but the conformation of the 'fast enzyme' remains obscure. In this study we demonstrated how oxygen binding at haem a3 could trigger long distance conformational changes and then simulated a conformational change in an eight residue loop near to the enzyme's substrate (cytochrome c) binding site. We then used this modified COX to simulate a stable COX-cytochrome c ES-complex. Compared to ES-complexes formed in the absence of the conformation change, the distance between the redox centres of the two proteins was reduced by half and instead of nine, only four COX amino acid residues were found along the axis linking the electron entry point and the CuA redox centre of COX: We proposed that intramolecular electron transfer in COX occurs via a charge/hydrogen relay system involving these four residues. We suggest that the conformational change and resulting shortened electron pathway are features of fast-acting COX. This article is protected by copyright. All rights reserved.

  8. Protein C and S deficiency presenting as acute abdomen

    Directory of Open Access Journals (Sweden)

    Amit A Bharadiya

    2015-01-01

    Full Text Available Protein C and S are essential in limiting the activation of coagulation in vivo. Their deficiencies predispose the patient to thrombophilia and leads to thrombosis, often at unusual sites. Arterial thrombosis is rarely observed. We report a case of a patient with abdominal arteriovenous thrombosis leading to multiorgan infarction secondary to deficiency of protein C and protein S and presenting as acute abdomen.

  9. Iron uptake in ferritin is blocked by binding of [Cr(TREN)(H(2)O)(OH)](2+), a slow dissociating model for [Fe(H(2)O)(6)](2+).

    Science.gov (United States)

    Barnés, Carmen M; Theil, Elizabeth C; Raymond, Kenneth N

    2002-04-16

    Ferritin concentrates iron as a hydrous ferric oxide in a protein cavity (8 nm in diameter) by using eight pores along the threefold symmetry axes of the octahedral supramolecular structure. The role of ligand exchange in the entry of Fe(II) hexahydrate into ferritin protein has been studied with [Cr(TREN)(H(2)O)(OH)](2+) [TREN = N(CH(2)CH(2)NH(2))(3)], a model for Fe(H(2)O)(6)2+ with only two exchangeable ligands. The results show that five different ferritin proteins, varying in pore structure, oxidation sites, and nucleation sites, bind Cr(TREN) at functional protein sites, based on inhibition of iron mineralization and oxidation. Properties of Cr(TREN)-ferritin adducts include an increased isoelectric point, a shift in the Cr(TREN) UV/vis spectrum consistent with exchange of water for protein carboxylate or thiolate ligands, binding affinities of 50-250 microM, and a slow rate of dissociation (k = 4 x 10(-6) sec(-1)). The relationship of Cr(TREN) inhibition of iron oxidation and mineralization by Cr(TREN) to the known structures of the various ferritins tested suggests that Cr(TREN) plugs the ferritin pores, obstructing Fe(II) entry in folded and unfolded pores. Because only two exchangeable waters are sufficient for pore binding of Cr(TREN), the physiological Fe(II) donor must bind to the pore with few exchangeable ligands. These results show the advantage of using stable model complexes to explore properties of transient Fe-protein complexes during Fe mineralization in ferritin.

  10. 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

  11. Slow Pseudotachylites

    Science.gov (United States)

    Pec, M.; Stunitz, H.; Heilbronner, R.

    2011-12-01

    Tectonic pseudotachylites as solidified, friction induced melts are believed to be the only unequivocal evidence for paleo-earthquakes. Earthquakes occur when fast slip (1 - 3 m/s) propagates on a localized failure plane and are always related with stress drops. The mechanical work expended, together with the rock composition and the efficiency of thermal dissipation, controls whether the temperature increase on a localized slip plane will be sufficient to induce fusion. We report the formation of pseudotachylites during steady-state plastic flow at slow bulk shear strain rates (~10^-3 to ~10^-5 /s corresponding to slip rates of ~10^-6 to ~10^-8 m/s) in experiments performed at high confining pressures (500 MPa) and temperatures (300°C) corresponding to a depth of ~15 km. Crushed granitioid rock (Verzasca gneiss), grain size ≤ 200 μm, with 0.2 wt% water added was placed between alumina forcing blocks pre-cut at 45°, weld-sealed in platinum jackets and deformed with a constant displacement rate in a solid medium deformation apparatus (modified Griggs rig). Microstructural observations show the development of a S-C-C' fabric with C' slip zones being the dominant feature. Strain hardening in the beginning of the experiment is accompanied with compaction which is achieved by closely spaced R1 shears pervasively cutting the whole gouge zone and containing fine-grained material (d 10) are localized in less densely spaced, ~10 μm thick C'-C slip zones which develop predominantly in feldspars and often contain micas. In TEM, they appear to have no porosity consisting of partly amorphous material and small crystalline fragments with the average grain size of 20 nm. After the peak strength, the samples weaken by ~20 MPa and continue deforming up to γ ~ 4 without any stress drops. Strain localization progresses in the C'-C slip zones and leads to the formation of pseudotachylites. Rough estimates of slip rates in the deforming slip zones are 2 to 4 orders of magnitude

  12. [Activated protein C (the impact of PROWESS trial)].

    Science.gov (United States)

    Iba, Toshiaki; Kidokoro, Akio

    2004-12-01

    The inflammatory response in severe sepsis is integrally linked to procoagulant activity and endothelial activation. The abnormalities in the microcirculation results in the development of septic organ dysfunction. The natural anticoagulant activated protein C is expected not only to improve the unbalanced coagulation/fibrinolysis system, but also to modulate the endothelial function, and to express the anti-inflammatory properties. To certify these effects, a large scale, multiple center, randomized, placebo controlled phase 3 trial (PROWESS trial) has been conducted. The results showed the statistically significant improved survival in patients with sepsis induced organ dysfunction (absolute risk reduction in 6.1%). As a result, activated protein C is recommended in patients at high risk of death such as Acute Physiology and Chronic Health Evaluation II > or = 25. However, since bleeding risk is reported as an adverse effect, activated protein C is contraindicated in patients with bleeding tendency.

  13. 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.

  14. 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.

  15. FROM SLOW FOOD TO SLOW TOURISM

    Directory of Open Access Journals (Sweden)

    Bac Dorin Paul

    2014-12-01

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

  16. Synergistic inhibition of the intrinsic factor X activation by protein S and C4b-binding protein

    NARCIS (Netherlands)

    Koppelman, S.J.

    1995-01-01

    The complement protein C4b-binding protein plays an important role in the regulation of the protein C anticoagulant pathway. C4b-binding protein can bind to protein S, thereby inhibiting the cofactor activity of protein S for activated protein C. In this report, we describe a new role for C4b-bindin

  17. 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.

  18. 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

  19. Protein C and acute inflammation: a clinical and biological perspective.

    Science.gov (United States)

    Christiaans, Sarah C; Wagener, Brant M; Esmon, Charles T; Pittet, Jean Francois

    2013-10-01

    The protein C system plays an active role in modulating severe systemic inflammatory processes such as sepsis, trauma, and acute respiratory distress syndrome (ARDS) via its anticoagulant and anti-inflammatory properties. Plasma levels of activated protein C (aPC) are lower than normal in acute inflammation in humans, except early after severe trauma when high plasma levels of aPC may play a mechanistic role in the development of posttraumatic coagulopathy. Thus, following positive results of preclinical studies, a clinical trial (PROWESS) with high continuous doses of recombinant human aPC given for 4 days demonstrated a survival benefit in patients with severe sepsis. This result was not confirmed by subsequent clinical trials, including the recently published PROWESS-SHOCK trial in patients with septic shock and a phase II trial with patients with nonseptic ARDS. A possible explanation for the major difference in outcome between PROWESS and PROWESS-SHOCK trials is that lung-protective ventilation was used for the patients included in the recent PROWESS-SHOCK, but not in the original PROWESS trial. Since up to 75% of sepsis originates from the lung, aPC treatment may not have added enough to the beneficial effect of lung-protective ventilation to show lower mortality. Thus whether aPC will continue to be used to modulate the acute inflammatory response in humans remains uncertain. Because recombinant human aPC has been withdrawn from the market, a better understanding of the complex interactions between coagulation and inflammation is needed before considering the development of new drugs that modulate both coagulation and acute inflammation in humans.

  20. Too slow, for Milton

    OpenAIRE

    Armstrong, N.

    2011-01-01

    Too slow, for Milton was written in 2011, as part of a memorial project for Milton Babbitt. The piece borrows harmonies from Babbitt's Composition for 12 Instruments (harmonies which Babbitt had in turn borrowed from Schoenberg's Ode to Napoleon), but unfolds them as part of a musical texture characterised by repetition, resonance, and a slow rate of change. As Babbitt once told me that my music was 'too slow', this seemed an appropriately obstinate form of homage.

  1. 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...

  2. 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.

  3. A comparative study of the protein C system in mother's blood, cord blood and amniotic fluid.

    OpenAIRE

    Ewa Zekanowska; Waldemar Uszyński; Mieczysław Uszyński; Jarosław Kuczyński; Marek Szymański

    2010-01-01

    Activated protein C (APC) is an important anticoagulant which plays a role in pathophysiology of pregnancy, e.g. in maintenance of the uteroplacental circulation and development of the fetus as well as in pathogenesis of preeclampsia. The study objective was to compare the levels of the respective components of the protein C system (protein C, PC; protein S, PS; thrombomodulin, TM) as well as thrombin activatable fibrinolysis inhibitor - TAFI in mother's blood, cord blood and amniotic fluid. ...

  4. Endothelial protein C receptor-expressing hematopoietic stem cells reside in the perisinusoidal niche in fetal liver.

    Science.gov (United States)

    Iwasaki, Hiroko; Arai, Fumio; Kubota, Yoshiaki; Dahl, Maria; Suda, Toshio

    2010-07-29

    Hematopoietic stem cells (HSCs) are maintained in specialized niches in adult bone marrow. However, niche and HSC maintenance mechanism in fetal liver (FL) still remains unclear. Here, we investigated the niche and the molecular mechanism of HSC maintenance in mouse FL using HSCs expressing endothelial protein C receptor (EPCR). The antiapoptotic effect of activated protein C (APC) on EPCR(+) HSCs and the expression of protease-activated receptor 1 (Par-1) mRNA in these cells suggested the involvement of the cytoprotective APC/EPCR/Par-1 pathway in HSC maintenance. Immunohistochemistry revealed that EPCR(+) cells were localized adjacent to, or integrated in, the Lyve-1(+) sinusoidal network, where APC and extracellular matrix (ECM) are abundant, suggesting that HSCs in FL were maintained in the APC- and ECM-rich perisinusoidal niche. EPCR(+) HSCs were in a relatively slow cycling state, consistent with their high expression levels of p57 and p18. Furthermore, the long-term reconstitution activity of EPCR(+) HSCs decreased significantly after short culture but not when cocultured with feeder layer of FL-derived Lyve-1(+) cells, which suggests that the maintenance of the self-renewal activity of FL HSCs largely depended on the interaction with the perisinusoidal niche. In conclusion, EPCR(+) HSCs resided in the perisinusoidal niche in mouse FL.

  5. C-terminal, endoplasmic reticulum-lumenal domain of prosurfactant protein C - structural features and membrane interactions.

    Science.gov (United States)

    Casals, Cristina; Johansson, Hanna; Saenz, Alejandra; Gustafsson, Magnus; Alfonso, Carlos; Nordling, Kerstin; Johansson, Jan

    2008-02-01

    Surfactant protein C (SP-C) constitutes the transmembrane part of prosurfactant protein C (proSP-C) and is alpha-helical in its native state. The C-terminal part of proSP-C (CTC) is localized in the endoplasmic reticulum lumen and binds to misfolded (beta-strand) SP-C, thereby preventing its aggregation and amyloid fibril formation. In this study, we investigated the structure of recombinant human CTC and the effects of CTC-membrane interaction on protein structure. CTC forms noncovalent trimers and supratrimeric oligomers. It contains two intrachain disulfide bridges, and its secondary structure is significantly affected by urea or heat only after disulfide reduction. The postulated Brichos domain of CTC, with homologs found in proteins associated with amyloid and proliferative disease, is up to 1000-fold more protected from limited proteolysis than the rest of CTC. The protein exposes hydrophobic surfaces, as determined by CTC binding to the environment-sensitive fluorescent probe 1,1'-bis(4-anilino-5,5'-naphthalenesulfonate). Fluorescence energy transfer experiments further reveal close proximity between bound 1,1'-bis(4-anilino-5,5'-naphthalenesulfonate) and tyrosine residues in CTC, some of which are conserved in all Brichos domains. CTC binds to unilamellar phospholipid vesicles with low micromolar dissociation constants, and differential scanning calorimetry and CD analyses indicate that membrane-bound CTC is less structurally ordered than the unbound protein. The exposed hydrophobic surfaces and the structural disordering that result from interactions with phospholipid membranes suggest a mechanism whereby CTC binds to misfolded SP-C in the endoplasmic reticulum membrane.

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

    Directory of Open Access Journals (Sweden)

    Thomas A Prohaska

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

  7. 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.

  8. Slowing Kidney Disease

    Science.gov (United States)

    ... takes years of daily use for NSAIDs to cause CKD. But, once CKD is present, NSAIDs can make ... in the wrong places can “oxidize” and cause damage, a lot like rust. Antioxidants ... Fish oil can help slow CKD that is caused by a disease called IgA ...

  9. [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.

  10. 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.

  11. 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:

  12. 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

  13. 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.

  14. 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.

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

    NARCIS (Netherlands)

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

    1993-01-01

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

  16. 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.

  17. 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.

  18. Slow Scan Telemedicine

    Science.gov (United States)

    1984-01-01

    Originally developed under contract for NASA by Ball Bros. Research Corporation for acquiring visual information from lunar and planetary spacecraft, system uses standard closed circuit camera connected to a device called a scan converter, which slows the stream of images to match an audio circuit, such as a telephone line. Transmitted to its destination, the image is reconverted by another scan converter and displayed on a monitor. In addition to assist scans, technique allows transmission of x-rays, nuclear scans, ultrasonic imagery, thermograms, electrocardiograms or live views of patient. Also allows conferencing and consultation among medical centers, general practitioners, specialists and disease control centers. Commercialized by Colorado Video, Inc., major employment is in business and industry for teleconferencing, cable TV news, transmission of scientific/engineering data, security, information retrieval, insurance claim adjustment, instructional programs, and remote viewing of advertising layouts, real estate, construction sites or products.

  19. 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.

  20. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-03-29

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

  2. 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.

  3. Slow frictional waves

    Science.gov (United States)

    Viswanathan, Koushik; Sundaram, Narayan; Chandrasekar, Srinivasan

    Stick-slip, manifest as intermittent tangential motion between two dry solid surfaces, is a friction instability that governs diverse phenomena from automobile brake squeals to earthquakes. We show, using high-speed in situ imaging of an adhesive polymer interface, that low velocity stick-slip is fundamentally of three kinds, corresponding to passage of three different surface waves -- separation pulses, slip pulses and the well-known Schallamach waves. These waves, traveling much slower than elastic waves, have clear distinguishing properties. Separation pulses and Schallamach waves involve local interface separation, and propagate in opposite directions while slip pulses are characterized by a sharp stress front and do not display any interface detachment. A change in the stick-slip mode from separation to slip pulse is effected simply by increasing the normal force. Together, these three waves constitute all possible stick-slip modes in adhesive friction and are shown to have direct analogues in muscular locomotory waves in soft bodied invertebrates. A theory for slow wave propagation is also presented which is capable of explaining the attendant interface displacements, velocities and stresses.

  4. A Case for Slow Reading

    Directory of Open Access Journals (Sweden)

    Matthew J Ostercamp

    2014-05-01

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

  5. 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.

  6. Slow light and slow acoustic phonons in optophononic resonators

    Science.gov (United States)

    Villafañe, V.; Soubelet, P.; Bruchhausen, A. E.; Lanzillotti-Kimura, N. D.; Jusserand, B.; Lemaître, A.; Fainstein, A.

    2016-11-01

    Slow and confined light have been exploited in optoelectronics to enhance light-matter interactions. Here we describe the GaAs/AlAs semiconductor microcavity as a device that, depending on the excitation conditions, either confines or slows down both light and optically generated acoustic phonons. The localization of photons and phonons in the same place of space amplifies optomechanical processes. Picosecond laser pulses are used to study through time-resolved reflectivity experiments the coupling between photons and both confined and slow acoustic phonons when the laser is tuned either with the cavity (confined) optical mode or with the stop-band edge (slow) optical modes. A model that fully takes into account the modified propagation of the acoustic phonons and light in these resonant structures is used to describe the laser detuning dependence of the coherently generated phonon spectra and amplitude under these different modes of laser excitation. We observe that confined light couples only to confined mechanical vibrations, while slow light can generate both confined and slow coherent vibrations. A strong enhancement of the optomechanical coupling using confined photons and vibrations, and also with properly designed slow photon and phonon modes, is demonstrated. The prospects for the use of these optoelectronic devices in confined and slow optomechanics are addressed.

  7. 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.

  8. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Romeo, G.; Hassan, H.J.; Staempfli, S.; Roncuzzi, L.; Cianetti, L.; Leonardi, A.; Vicente, V.; Mannucci, P.M.; Bertina, R.; Peschile, C.; Cortese, R.

    1987-05-01

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

  10. 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

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

    Directory of Open Access Journals (Sweden)

    Dasnan Ismail

    2002-06-01

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

  12. INCREASE IN ACTIVATED PROTEIN C MEDIATES ACUTE TRAUMATIC COAGULOPATHY IN MICE

    Science.gov (United States)

    Chesebro, Brian B.; Rahn, Pamela; Carles, Michel; Esmon, Charles T.; Xu, Jun; Brohi, Karim; Frith, Daniel; Pittet, Jean-François; Cohen, Mitchell J.

    2013-01-01

    In severely injured and hypoperfused trauma patients, endogenous acute coagulopathy (EAC) is associated with an increased morbidity and mortality. Recent human data correlate this coagulopathy with activation of the protein C pathway. To examine the mechanistic role of protein C in the development of EAC, we used a mouse model of trauma and hemorrhagic shock, characterized by the combination of tissue injury and severe metabolic acidosis. Mice were subjected to one of four treatment groups: 1) C, control; 2) T, trauma (laparotomy); 3) H, hemorrhage (MAP, 35 mmHg × 60 min); 4) TH, trauma + hemorrhage. After 60 min, blood was drawn for analysis. Compared with C mice, the TH mice had a significantly elevated activated partial thromboplastin time (23.3 vs. 34.5 s) and significantly increased levels of activated protein C (aPC; 2.30 vs. 13.58 ng/mL). In contrast, T and H mice did not develop an elevated activated partial thromboplastin time or increased aPC. Selective inhibition of the anticoagulant property of aPC prevented the coagulopathy seen in response to trauma/hemorrhage (23.5 vs. 38.6 s [inhibitory vs. control monoclonal antibody]) with no impact on survival during the shock period. However, complete blockade of both the anticoagulant and cytoprotective functions of aPC caused 100% mortality within 45 min of shock, with histopathology evidence of pulmonary thrombosis and perivascular hemorrhage. These results indicate that our unique mouse model of T/H shock mimics our previous observations in trauma patients and demonstrates that EAC is mediated by the activation of the protein C pathway. In addition, the cytoprotective effect of protein C activation seems to be necessary for survival of the initial shock injury. PMID:19333141

  13. Perovskite photovoltaics: Slow recombination unveiled

    Science.gov (United States)

    Moser, Jacques-E.

    2017-01-01

    One of the most salient features of hybrid lead halide perovskites is the extended lifetime of their photogenerated charge carriers. This property has now been shown experimentally to originate from a slow, thermally activated recombination process.

  14. Birth control - slow release methods

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/007555.htm Birth control - slow release methods To use the sharing features on this page, please enable JavaScript. Certain birth control methods contain man-made forms of hormones. These ...

  15. 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.

  16. The protein C pathway in tissue inflammation and injury: pathogenic role and therapeutic implications.

    Science.gov (United States)

    Danese, Silvio; Vetrano, Stefania; Zhang, Li; Poplis, Victoria A; Castellino, Francis J

    2010-02-11

    Inflammation and coagulation are closely linked interdependent processes. Under physiologic conditions, the tissue microcirculation functions in anticoagulant and anti-inflammatory fashions. However, when inflammation occurs, coagulation is also set in motion and actively participates in enhancing inflammation. Recently, novel and unexpected roles of hemostasis in the humoral and cellular components of innate immunity have been described. In particular, the protein C system, besides its well-recognized role in anticoagulation, plays a crucial role in inflammation. Indeed, the protein C system is now emerging as a novel participant in the pathogenesis of acute and chronic inflammatory diseases, such as sepsis, asthma, inflammatory bowel disease, atherosclerosis, and lung and heart inflammation, and may emerge as unexpected therapeutic targets for intervention.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. Simultaneous Left Ventricular and Deep Vein Thrombi Caused by Protein C Deficiency

    Science.gov (United States)

    Nishiyama, Motohiro; Shirakawa, Motoaki

    2017-01-01

    Protein C deficiency is a risk of venous thrombosis because of poor fibrinolytic activity. It remains controversial whether protein C deficiency causes arterial thrombosis. A 21-year-old woman was referred with a chief complaint of right leg pain and numbness. Contrast-enhanced computed tomography revealed a low-density mass in the left ventricle (LV), splenic infarction, and peripheral arterial obstructions in her right leg. Thrombosis extending from the renal vein to the inferior vena cava was also detected. Electrocardiography revealed ST depression in leads II, III, and aVF. Transthoracic echocardiography revealed hypokinesis of the apex and interventricular septum and a hypoechoic mass in the LV (26 × 20 mm). She was diagnosed with acute arterial obstruction caused by the LV thrombus, which might have resulted from previous myocardial infarction. Protein C activation turned out to be low (41%) 5 days after admission. The anticoagulant therapy was switched from heparin to rivaroxaban 16 days after admission. The LV thrombus disappeared 24 days after initial treatment, and she has had no thrombotic episodes for 2.8 years under rivaroxaban therapy. Thrombophilia should be investigated for cases of simultaneous left ventricular and deep venous thrombi. Rivaroxaban can be effective in prevention of further thrombotic events. PMID:28194181

  3. 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.

  4. Slow internal protein dynamics in solution

    Science.gov (United States)

    Biehl, R.; Richter, D.

    2014-12-01

    Large-scale domain dynamics in proteins are found when flexible linkers or hinges connect domains. The related conformational changes are often related to the function of the protein, for example by arranging the active center after substrate binding or allowing transport and release of products. The adaptation of a specific active structure is referred to as ‘induced fit’ and is challenged by models such as ‘conformational sampling’. Newer models about protein function include some flexibility within the protein structure or even internal dynamics of the protein. As larger domains contribute to the configurational changes, the timescale of the involved motions is slowed down. The role of slow domain dynamics is being increasingly recognized as essential to understanding the function of proteins. Neutron spin echo spectroscopy (NSE) is a technique that is able to access the related timescales from 0.1 up to several hundred nanoseconds and simultaneously covers the length scale relevant for protein domain movements of several nanometers distance between domains. Here we focus on these large-scale domain fluctuations and show how the structure and dynamics of proteins can be assessed by small-angle neutron scattering and NSE.

  5. Dose from slow negative muons.

    Science.gov (United States)

    Siiskonen, T

    2008-01-01

    Conversion coefficients from fluence to ambient dose equivalent, from fluence to maximum dose equivalent and quality factors for slow negative muons are examined in detail. Negative muons, when stopped, produce energetic photons, electrons and a variety of high-LET particles. Contribution from each particle type to the dose equivalent is calculated. The results show that for the high-LET particles the details of energy spectra and decay yields are important for accurate dose estimates. For slow negative muons the ambient dose equivalent does not always yield a conservative estimate for the protection quantities. Especially, the skin equivalent dose is strongly underestimated if the radiation-weighting factor of unity for slow muons is used. Comparisons to earlier studies are presented.

  6. 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

  7. 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.

  8. 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

  9. Characterization of RyR1-slow, a ryanodine receptor specific to slow-twitch skeletal muscle.

    Science.gov (United States)

    Morrissette, J; Xu, L; Nelson, A; Meissner, G; Block, B A

    2000-11-01

    Two distinct skeletal muscle ryanodine receptors (RyR1s) are expressed in a fiber type-specific manner in fish skeletal muscle (11). In this study, we compare [(3)H]ryanodine binding and single channel activity of RyR1-slow from fish slow-twitch skeletal muscle with RyR1-fast and RyR3 isolated from fast-twitch skeletal muscle. Scatchard plots indicate that RyR1-slow has a lower affinity for [(3)H]ryanodine when compared with RyR1-fast. In single channel recordings, RyR1-slow and RyR1-fast had similar slope conductances. However, the maximum open probability (P(o)) of RyR1-slow was threefold less than the maximum P(o) of RyR1-fast. Single channel studies also revealed the presence of two populations of RyRs in tuna fast-twitch muscle (RyR1-fast and RyR3). RyR3 had the highest P(o) of all the RyR channels and displayed less inhibition at millimolar Ca(2+). The addition of 5 mM Mg-ATP or 2.5 mM beta, gamma-methyleneadenosine 5'-triphosphate (AMP-PCP) to the channels increased the P(o) and [(3)H]ryanodine binding of both RyR1s but also caused a shift in the Ca(2+) dependency curve of RyR1-slow such that Ca(2+)-dependent inactivation was attenuated. [(3)H]ryanodine binding data also showed that Mg(2+)-dependent inhibition of RyR1-slow was reduced in the presence of AMP-PCP. These results indicate differences in the physiological properties of RyRs in fish slow- and fast-twitch skeletal muscle, which may contribute to differences in the way intracellular Ca(2+) is regulated in these muscle types.

  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. 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.

  12. 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.

  13. Plasma levels of the anti-coagulation protein C and the risk of ischaemic heart disease. A Mendelian randomisation study.

    Science.gov (United States)

    Schooling, C Mary; Zhong, Yi

    2017-01-26

    Protein C is an environmentally modifiable anticoagulant, which protects against venous thrombosis, whether it also protects against ischaemic heart disease is unclear, based on observational studies and relatively small genetic studies. It was our study aim to clarify the role of protein C in ischaemic heart disease. The risk of coronary artery disease/myocardial infarction (CAD/MI) was assessed according to genetically predicted protein C in very large studies. Associations with lipids and diabetes were similarly assessed to rule out effects via traditional cardiovascular disease risk factors. Separate sample instrumental variable analysis with genetic instruments (Mendelian randomisation) was used to obtain an unconfounded estimate of the association of protein C (based on (rs867186 (PROCR), rs3746429 (EDEM2), rs7580658 (inter/PROC)) with CAD/MI in an extensively genotyped case (n=64374)-control (n=130681) study, CARDIoGRAMplusC4D. Associations with lipids and diabetes were similarly assessed using the Global Lipids Genetics Consortium Results (n=196,475) and the DIAbetes Genetics Replication And Meta-analysis case (n=34,380)-control (n=114,981) study. Genetically predicted protein C was negatively associated with CAD/MI, odds ratio (OR) 0.85 µg/ml, 95 % confidence interval 0.80 to 0.90, but had no such negative association with lipids or diabetes. Results were similar for the SNP rs867186 functionally relevant to protein C, and including additional potentially pleiotropic SNPs (rs1260326 (GCKR), rs17145713 (BAZ1B) and rs4321325 (CYP27C1)). In conclusion, protein C may protect against CAD/MI. Whether environmental or dietary items that raise protein C protect against ischaemic cardiovascular disease by that mechanism should be investigated.

  14. 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.

  15. 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.

  16. 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....

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

    Directory of Open Access Journals (Sweden)

    Anna Tarocco

    2015-01-01

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

  18. Two novel mutations in surfactant protein-C, lung function and obstructive lung disease

    DEFF Research Database (Denmark)

    Baekvad-Hansen, Marie; Nordestgaard, Børge G; Tybjaerg-Hansen, Anne;

    2010-01-01

    Dominant mutations in the surfactant protein-C(SFTPC) gene have been linked with interstitial lung disease. The frequency of lung disease due to SFTPC mutations in the general population is unknown. The aim of this study was to identify novel SFTPC mutations that are associated with lung function...... pulmonary disease or interstitial lung disease. No Y106X heterozygotes suffered from asthma, chronic obstructive pulmonary disease (COPD), or interstitial lung disease. We identified two novel mutations in highly conserved areas of the SFTPC gene, and show that heterozygotes for the mutations have normal...... lung function and are unaffected by COPD and interstitial lung disease. A53T heterozygotes had increased asthma risk, but further research is required to conclusively determine whether this mutation is associated with asthma....

  19. 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.

  20. 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.

  1. Six missense mutations associated with type I and type II protein C deficiency and implications obtained from molecular modelling.

    Science.gov (United States)

    Zheng, Y Z; Sakata, T; Matsusue, T; Umeyama, H; Kato, H; Miyata, T

    1994-10-01

    The molecular basis of protein C deficiency was studied in three type I and three type II heterozygotes. Three probands showed thrombotic complications. All the exons and intron/exon junctions of the protein C gene were studied using a strategy combining by the polymerase chain reaction (PCR) amplification, single-strand conformational polymorphism (SSCP) analysis, and DNA sequencing of the PCR-amplified fragments. Six missense mutations were identified, including three novel ones. One was located in exon II, in which the initiating translation codon (ATG) encoding for Met at position -42 was replaced by ACG encoding for Thr. The other five were located in exon IX, and included TAC(Tyr399)-->CAC(His), CCG(Pro327)-->CTG(Leu), GAC(Asp359)-->AAC(Asn) in two cases, and GGG(Gly350)-->AGG(Arg). Four of the six missense mutations occurred in CG dinucleotide. Sequence analysis of the other exons excluded additional mutations. By restriction enzyme analysis, co-segregation of the mutation with protein C deficiency was observed in four families. The other two mutations at amino acid positions -42 and 350 were also considered to be associated with protein C deficiency due to the absence of these mutations in 50 normal individuals. A structural model of the protease domain of mutant activated protein C was constructed by the chimeric modelling method, and the resultant model suggested conformational changes due to each missense mutation identified in protein C deficiency. The present data also provide some evidence regarding the genetic heterogeneity of protein C deficiency.

  2. Plasma protein C levels in immunocompromised septic patients are significantly lower than immunocompetent septic patients: a prospective cohort study

    Directory of Open Access Journals (Sweden)

    Bird Robert

    2009-10-01

    Full Text Available Abstract Introduction Activated Protein C [APC] improves outcome in immunocompetent patients with severe sepsis particularly in those who are perceived to have high mortality risk. Before embarking on a trial of APC administration in immunocompromised septic patients, a preliminary study on plasma levels of protein C in this cohort is essential. Objective To assess serum Protein C concentrations in immunocompromised patients as compared to immunocompetent patients during sepsis, severe sepsis, septic shock and recovery. Methods Prospective cohort study in a tertiary hospital. Patients satisfying inclusion criteria were enrolled after informed consent. Clinical variables were noted with sample collection when patients met criteria for sepsis, severe sepsis, septic shock and recovery. Protein C levels were measured using monoclonal antibody based fluorescence immunoassay. Results Thirty one patients participated in this study (22 immunocompromised, 9 immunocompetent. Protein C levels were found to be significantly lower in the immunocompromised group compared to the immunocompetent group, particularly observed in severe sepsis [2.27 (95% CI: 1.63-2.9 vs 4.19 (95% CI: 2.87-5.52 mcg/ml] (p = 0.01 and sepsis [2.59 (95% CI: 1.98-3.21 vs 3.64 (95% CI: 2.83-4.45 mcg/ml] (p = 0.03. SOFA scores were similar in both the groups across sepsis, severe sepsis and septic shock categories. Protein C levels improved significantly in recovery (p = 0.001 irrespective of immune status. Conclusion Protein C levels were significantly lower in immunocompromised patients when compared to immunocompetent patients in severe sepsis and sepsis categories. Our study suggests a plausible role for APC in severely septic immunocompromised patients which need further elucidation.

  3. Inherited ataxia with slow saccades

    Directory of Open Access Journals (Sweden)

    R T Chakor

    2012-01-01

    Full Text Available Ataxia is a symptom of cerebellar dysfunction. Slowly progressive ataxia, dysarthria in an adult with a positive family history suggests an inherited cerebellar ataxia. We present an adult with gradually progressive ataxia and slow saccades. There was history of similar illness in his son. Genetic testing for spinocerebellar ataxia 2 was positive. We discuss the various inherited ataxias, causes of acute, progressive ataxia syndromes, episodic ataxias and ataxia associated with other neurological signs like peripheral neuropathy, pyramidal features, movement disorders and cognitive decline.

  4. Can Occupational Therapy Slow Alzheimer's Decline?

    Science.gov (United States)

    ... news/fullstory_162135.html Can Occupational Therapy Slow Alzheimer's Decline? Patients, caregivers may reap some benefits, but ... slow down the physical decline that comes with Alzheimer's disease, a new clinical trial suggests. The study ...

  5. 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

  6. 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....

  7. Slow Monitoring Systems for CUORE

    Science.gov (United States)

    Dutta, Suryabrata; Cuore Collaboration

    2016-09-01

    The Cryogenic Underground Observatory for Rare Events (CUORE) is a ton-scale neutrinoless double-beta decay experiment under construction at the Laboratori Nazionali del Gran Sasso (LNGS). The experiment is comprised of 988 TeO2 bolometric crystals arranged into 19 towers and operated at a temperature of 10 mK. We have developed slow monitoring systems to monitor the cryostat during detector installation, commissioning, data taking, and other crucial phases of the experiment. Our systems use responsive LabVIEW virtual instruments and video streams of the cryostat. We built a website using the Angular, Bootstrap, and MongoDB frameworks to display this data in real-time. The website can also display archival data and send alarms. I will present how we constructed these slow monitoring systems to be robust, accurate, and secure, while maintaining reliable access for the entire collaboration from any platform in order to ensure efficient communications and fast diagnoses of all CUORE systems.

  8. 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.

  9. 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

  10. Highly Alfvenic Slow Solar Wind

    Science.gov (United States)

    Roberts, D. Aaron

    2010-01-01

    It is commonly thought that fast solar wind tends to be highly Alfvenic, with strong correlations between velocity and magnetic fluctuations, but examples have been known for over 20 years in which slow wind is both Alfvenic and has many other properties more typically expected of fast solar wind. This paper will present a search for examples of such flows from more recent data, and will begin to characterize the general characteristics of them. A very preliminary search suggests that such intervals are more common in the rising phase of the solar cycle. These intervals are important for providing constraints on models of solar wind acceleration, and in particular the role waves might or might not play in that process.

  11. 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.

  12. 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.

  13. Coupled-cavity-based slow light metamaterials with antireflection structures

    Science.gov (United States)

    Lee, Sun-Goo; Kim, Seong-Han; Jung, Soo-Yong; Lee, Jongjin; Park, Jong-Moon; Kee, Chul-Sik

    2016-11-01

    A slow light metamaterial based on a coupled Fabry-Pérot cavity is proposed and numerically studied using finite-difference time-domain simulations. The coupled cavity-based slow light metamaterial is composed of a periodic array of partial mirrors with low transmittance, i.e., thin metal films perforated with a subwavelength hole array. The tight-binding model is employed to investigate the transmission properties of the coupled-cavity-based metamaterial. It is shown that the group velocities of the slowly propagating modes can be controlled by adjusting the radius of holes in the mirrors. We also show that undesirable reflections at the boundaries of the finite-size metamaterial can be minimized by introducing optimized antireflection structures.

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

    Science.gov (United States)

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

    2016-05-23

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

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

    Science.gov (United States)

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

    2009-04-01

    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-kappaB 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 Cdk1 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 Chk1 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.

  16. 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.

  17. Analytical performances of Hemoclot Protein C Reagent on ACL TOP analyzer.

    Science.gov (United States)

    Calmette, Leyla; Charpentier, Nicole; Tircot, Caroline; Bigot, Delphine; Dunois, Claire; Amiral, Jean; Tetegan, Marcelle; Sep Hieng, Sonnthida; Peltier, Jean-Yves

    2016-12-01

    Our study aimed to evaluate and validate according to standard NF EN ISO 15189 the original protocol ajustement of Hemoclot Protein C (PC) (Hyphen BioMed), clotting-based assay of PC on ACL TOP analyzer (Werfen/Instrumentation Laboratory). We evaluated the performance in terms of imprecision and we validate additional parameters in range B required by the SH GTA 04 (COFRAC): repeatability, reproducibility, detection and quantification limits, limits of linearity, stability, inter-samples and inter-reagents contamination, inaccuracy, evaluation of interferences (hemolysis, bilirubinemia and chyles). A comparison with Hemoclot PC on STA Compact analyzer (Stago) was performed. Coefficients of variation were lower than 5 %. Detection and quantification limits were respectively 8.3 % and 9.3 %. Superior limit of linearity was 140 %. The test didn't diplay any inter-samples and inter-reagents contamination. Reagent after reconstitution was stable 6 hours on ACL TOP. No interferences were observed for hemoglobin lower than 500 mg/dL, for bilirubin lower than and for chyles lower than 300 mg/dL. Comparison with Hemoclot PC on STA analyzer (Stago) was satisfactory. Hemoclot PC adjusted on ACL TOP analyzer showed satisfactory analytical performances with criteria chosen in our study. These data allow a better knowledge of the performances of this test and were useful to make a validation file in range B as recommended by SH GTA 04.

  18. 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.

  19. 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.

  20. 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.

  1. Activated protein C protection from lung inflammation in endotoxin-induced injury.

    Science.gov (United States)

    Pirrone, Federica; Mazzola, Silvia M; Pastore, Camilla; Paltrinieri, Saverio; Sironi, Giuseppe; Riccaboni, Pietro; Viola, Manuela; Passi, Alberto; Clement, Maria G; Albertini, Mariangela

    2008-11-01

    We studied the protection of recombinant human activated protein C (rhAPC) in endotoxin-induced lung inflammation and injury and whether this effect is correlated with modulation of lung matrix metalloproteinase (MMP) activity. We randomly assigned 12 Large White pigs to receive intravenous Escher-ichia coli lipopolysaccharide (LPS; 40 mu g/kg/hr), rhAPC (24 mu g/ kg/hr), or both. We monitored respiratory mechanics and function, cell counts, and cytokine concentrations in bron-choalveolar lavage fluid (BALF). Lung samples were collected for the zymography of MMP-2 and MMP-9 activities and for histology. In septic pigs, rhAPC decreased proMMP-9 release as well as MMP-9 activation, and increased proMMP-2 presence without any evident activation compared with specimens that were given LPS alone. In addition, lung injury in rhAPC-treated animals was significantly attenuated, as shown by higher respiratory compliance, delayed increase in tumor necrosis alfa and interleukin-1beta as well as neutrophil recruitment in the BALF, reduced lung edema, and histologic changes. In conclusion, rhAPC is beneficial in acute lung injury, and the protection may depend, at least in part, on modulation of MMP-2/9 activity.

  2. Endothelial protein C receptor function in murine and human breast cancer development.

    Directory of Open Access Journals (Sweden)

    Florence Schaffner

    Full Text Available Several markers identify cancer stem cell-like populations, but little is known about the functional roles of stem cell surface receptors in tumor progression. Here, we show that the endothelial protein C receptor (EPCR, a stem cell marker in hematopoietic, neuronal and epithelial cells, is crucial for breast cancer growth in the orthotopic microenvironment of the mammary gland. Mice with a hypomorphic allele of EPCR show reduced tumor growth in the PyMT-model of spontaneous breast cancer development and deletion of EPCR in established PyMT tumor cells significantly attenuates transplanted tumor take and growth. We find expansion of EPCR(+ cancer stem cell-like populations in aggressive, mammary fat pad-enhanced human triple negative breast cancer cells. In this model, EPCR-expressing cells have markedly increased mammosphere- and tumor-cell initiating activity compared to another stable progenitor-like subpopulation present at comparable frequency. We show that receptor blocking antibodies to EPCR specifically attenuate in vivo tumor growth initiated by either EPCR(+ cells or the heterogenous mixture of EPCR(+ and EPCR(- cells. Furthermore, we have identified tumor associated macrophages as a major source for recognized ligands of EPCR, suggesting a novel mechanism by which cancer stem cell-like populations are regulated by innate immune cells in the tumor microenvironment.

  3. 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.

  4. 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....

  5. Slowing Down Surface Plasmons on a Moiré Surface

    Science.gov (United States)

    Kocabas, Askin; Senlik, S. Seckin; Aydinli, Atilla

    2009-02-01

    We have demonstrated slow propagation of surface plasmons on metallic Moiré surfaces. The phase shift at the node of the Moiré surface localizes the propagating surface plasmons and adjacent nodes form weakly coupled plasmonic cavities. Group velocities around vg=0.44c at the center of the coupled cavity band and almost a zero group velocity at the band edges are observed. A tight binding model is used to understand the coupling behavior. Furthermore, the sinusoidally modified amplitude about the node suppresses the radiation losses and reveals a relatively high quality factor (Q=103).

  6. 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

  7. 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.

  8. The Evaluation of Protein C Activity and Some Inflammatory Markers in Synovia of Patients Undergoing Total Knee Arthroplasty

    Directory of Open Access Journals (Sweden)

    Ahmet Ata Alturfan

    2011-06-01

    Full Text Available Objective: Total knee arthroplasty (TKA is a major risk factor for thrombosis in patients over 40 years of age and this risk persists for several weeks after the surgery. Since inflammatory mechanisms affect coagulation and the natural anticoagulant system, we aimed to investigate protein C activities and inflammatory markers in patients undergoing TKA surgery.Material and Methods: We included 20 osteoarthritis patients and 20 healthy controls. Protein C activity and tumor necrosis factor-α (TNF-α levels in plasma and synovia were evaluated by ELISA technique. Results: In the patient group, protein C activities decreased and TNF-α levels increased significantly both in synovia and plasma when compared with the controls. Erythrocyte sedimentation rate of the patient group was found to be significantly elevated in comparison to the controls. On the other hand, serum C reactive protein values increased insignificantly when compared to controls.Conclusion: The decreased activity of protein C and increased levels of inflammatory markers in preoperative plasma and synovia of the patient group may enhance the risk for developing thrombosis.

  9. 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

    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...

  10. 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.

  11. Antibody SPC-54 provides acute in vivo blockage of the murine protein C system.

    Science.gov (United States)

    Burnier, Laurent; Fernández, José A; Griffin, John H

    2013-04-01

    Multiple protective effects of pharmacological activated protein C (APC) are reported in several organ pathologies. To help evaluate the endogenous murine PC system, we characterized a rat monoclonal anti-mouse PC antibody, SPC-54, which inhibited the amidolytic and anticoagulant activities of murine APC by>95%. SPC-54 blocked active site titration of purified APC using the active site titrant, biotinylated FPR-chloromethylketone, showing that SPC-54 blocks access to APC's active site to inhibit all enzymatic activity. A single injection of SPC-54 (10mg/kg) neutralized circulating PC in mice for at least 7days, and immunoblotting and immuno-precipitation with protein G-agarose confirmed that SPC-54 in vivo was bound to PC in plasma. Pre-infusion of SPC-54 in tissue factor-induced murine acute thromboembolism experiments caused a major decrease in mean survival time compared to controls (7min vs. 42.5min, P=0.0016). SPC-54 decreased lung perfusion in this model by 54% when monitored by vascular perfusion methodologies using infrared fluorescence of Evans blue dye. In LD50 endotoxemia murine models, SPC-54 infused at 7hr after endotoxin administration increased mortality from 42% to 100% (PSPC-54 ablates in vitro and in vivo APC protective functions and enzymatic activity. The ability of SPC-54 to block the endogenous PC/APC system provides a powerful tool to understand better the role of the endogenous PC system in murine injury models and in cell bioassays and also to neutralize the enzymatic activities of murine APC in any assay system.

  12. 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.

  13. Slow dynamics in proteins and polymer chains

    Science.gov (United States)

    Hu, Chin-Kun

    2013-02-01

    How a biological system can maintain in a non-equilibrium state for a very long time and why proteins aggregate are still not well understood. In this paper, we first review critical slow down of the Ising model and slow relaxation of a spin-glass model at low temperatures. The data indicate that relaxation of the spin glass model at low temperatures can be slower than the critical slowing down of the Ising model. We then review recent molecular dynamics results for the slow relaxation of polymer chains and experimental data for the glassy behavior of collagen fibrils. The slow dynamics in polymer chains and collagen fibrils can provide clues for understanding why a biological system can maintain in a non-equilibrium state for a very long time, and how to slow down protein aggregation related to neurodegenerative diseases.

  14. Fast- or slow-inactivated state preference of Na+ channel inhibitors: a simulation and experimental study.

    Directory of Open Access Journals (Sweden)

    Robert Karoly

    2010-06-01

    Full Text Available Sodium channels are one of the most intensively studied drug targets. Sodium channel inhibitors (e.g., local anesthetics, anticonvulsants, antiarrhythmics and analgesics exert their effect by stabilizing an inactivated conformation of the channels. Besides the fast-inactivated conformation, sodium channels have several distinct slow-inactivated conformational states. Stabilization of a slow-inactivated state has been proposed to be advantageous for certain therapeutic applications. Special voltage protocols are used to evoke slow inactivation of sodium channels. It is assumed that efficacy of a drug in these protocols indicates slow-inactivated state preference. We tested this assumption in simulations using four prototypical drug inhibitory mechanisms (fast or slow-inactivated state preference, with either fast or slow binding kinetics and a kinetic model for sodium channels. Unexpectedly, we found that efficacy in these protocols (e.g., a shift of the "steady-state slow inactivation curve", was not a reliable indicator of slow-inactivated state preference. Slowly associating fast-inactivated state-preferring drugs were indistinguishable from slow-inactivated state-preferring drugs. On the other hand, fast- and slow-inactivated state-preferring drugs tended to preferentially affect onset and recovery, respectively. The robustness of these observations was verified: i by performing a Monte Carlo study on the effects of randomly modifying model parameters, ii by testing the same drugs in a fundamentally different model and iii by an analysis of the effect of systematically changing drug-specific parameters. In patch clamp electrophysiology experiments we tested five sodium channel inhibitor drugs on native sodium channels of cultured hippocampal neurons. For lidocaine, phenytoin and carbamazepine our data indicate a preference for the fast-inactivated state, while the results for fluoxetine and desipramine are inconclusive. We suggest that

  15. Mechanism of Modification, by Lidocaine, of Fast and Slow Recovery from Inactivation of Voltage-Gated Na⁺ Channels.

    Science.gov (United States)

    Gawali, Vaibhavkumar S; Lukacs, Peter; Cervenka, Rene; Koenig, Xaver; Rubi, Lena; Hilber, Karlheinz; Sandtner, Walter; Todt, Hannes

    2015-11-01

    The clinically important suppression of high-frequency discharges of excitable cells by local anesthetics (LA) is largely determined by drug-induced prolongation of the time course of repriming (recovery from inactivation) of voltage-gated Na(+) channels. This prolongation may result from periodic drug-binding to a high-affinity binding site during the action potentials and subsequent slow dissociation from the site between action potentials ("dissociation hypothesis"). For many drugs it has been suggested that the fast inactivated state represents the high-affinity binding state. Alternatively, LAs may bind with high affinity to a native slow-inactivated state, thereby accelerating the development of this state during action potentials ("stabilization hypothesis"). In this case, slow recovery between action potentials occurs from enhanced native slow inactivation. To test these two hypotheses we produced serial cysteine mutations of domain IV segment 6 in rNav1.4 that resulted in constructs with varying propensities to enter fast- and slow-inactivated states. We tested the effect of the LA lidocaine on the time course of recovery from short and long depolarizing prepulses, which, under drug-free conditions, recruited mainly fast- and slow-inactivated states, respectively. Among the tested constructs the mutation-induced changes in native slow recovery induced by long depolarizations were not correlated with the respective lidocaine-induced slow recovery after short depolarizations. On the other hand, for long depolarizations the mutation-induced alterations in native slow recovery were significantly correlated with the kinetics of lidocaine-induced slow recovery. These results favor the "dissociation hypothesis" for short depolarizations but the "stabilization hypothesis" for long depolarizations.

  16. Contraception. Slow train gathers speed.

    Science.gov (United States)

    Hampton, N; Kubba, A

    The otherwise slow pace of contraceptive research developments has recently quickened, with new products developed, more on the way, and encouraging new data emerging about existing methods. While the 1995 UK pill scare called attention to a differential in the risk of venous thromboembolism (VTE) between pills containing levonorgestrel or norethisterone and those containing desogestrel or gestodene, there is only an extremely small level of excess mortality attributable to third-generation progestogens, less than 2 per million women per year. Tentative evidence suggests that pills with less anti-estrogenic progestogens are neutral with regard to coronary artery disease. The pill remains extremely safe for healthy young women, although additional research with larger numbers of participants is warranted. Salient research findings are that the combined oral contraceptive pill may protect against colon cancer, the pill appears to offer no protection against bone fractures, new products contain less estrogen and have a shortened pill-free interval, a WHO paper showed no significant association between cardiovascular disease and the use of oral or injectable progestogens, a UK study showed no correlation between bone density and plasma estrogen concentrations among long-term users of depot medroxyprogesterone acetate, and a WHO controlled trial found a progestogen-only method of emergency contraception to be considerably more effective in preventing expected pregnancies than the Yuzpe regimen. The T 380 copper IUD provides very high protection against intrauterine and extrauterine pregnancies for 10 years and is now available in an improved inserting mechanism, the Mirena levonorgestrel-releasing IUD system is now licensed for 5 years, and the GyneFIX IUD implant is a frameless device fixed during insertion to the fundal myometrium.

  17. Slow-Equilibration Approximation in Kinetic Size Exclusion Chromatography.

    Science.gov (United States)

    Cherney, Leonid T; Krylov, Sergey N

    2016-04-05

    Kinetic size exclusion chromatography with mass spectrometry detection (KSEC-MS) is a solution-based label-free approach for studying kinetics of reversible binding of a small molecule to a protein. Extraction of kinetic data from KSEC-MS chromatograms is greatly complicated by the lack of separation between the protein and protein-small molecule complex. As a result, a sophisticated time-consuming numerical approach was used for the determination of rate constants in the proof-of-principle works on KSEC-MS. Here, we suggest the first non-numerical (analytical) approach for finding rate constants of protein-small molecule interaction from KSEC-MS data. The approach is based on the slow-equilibration approximation, which is applicable to KSEC-MS chromatograms that reveal two peaks. The analysis of errors shows that the slow-equilibration approximation guarantees that the errors in the rate constants are below 20% if the ratio between the characteristic separation and equilibration times does not exceed 0.1. The latter condition can typically be satisfied for specific interactions such as receptor-ligand or protein-drug. The suggested analytical solution equips analytical scientists with a simple and fast tool for processing KSEC-MS data. Moreover, a similar approach can be potentially developed for kinetic analysis of protein-small molecule binding by other kinetic-separation methods such as nonequilibrium capillary electrophoresis of equilibrium mixtures (NECEEM).

  18. 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

  19. Can Fast and Slow Intelligence Be Differentiated?

    Science.gov (United States)

    Partchev, Ivailo; De Boeck, Paul

    2012-01-01

    Responses to items from an intelligence test may be fast or slow. The research issue dealt with in this paper is whether the intelligence involved in fast correct responses differs in nature from the intelligence involved in slow correct responses. There are two questions related to this issue: 1. Are the processes involved different? 2. Are the…

  20. 49 CFR 236.813 - Speed, slow.

    Science.gov (United States)

    2010-10-01

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

  1. 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.

  2. 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.

  3. Connecting slow earthquakes to huge earthquakes

    Science.gov (United States)

    Obara, Kazushige; Kato, Aitaro

    2016-07-01

    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.

  4. Guidance on patient Identification and Administration of Recombinant Human Activated protein C for the Treatment of Severe Sepsis

    Directory of Open Access Journals (Sweden)

    Gary Garber

    2002-01-01

    Full Text Available Approximately one-third of cases of severe sepsis result in death. Endogenous activated protein C (ApC plays a key role in the regulation of the inflammation, fibrinolysis and coagulation associated with severe sepsis. In a recently published phase III trial, protein C Worldwide Evaluation in Severe Sepsis (pROWESS, intravenous administration of recombinant human ApC (rhApC 24 µg/kg/h for 96 h to patients with severe sepsis resulted in a 6.1% reduction in absolute mortality and a 19.4% reduction in the relative risk of death from any cause within 28 days (number needed to treat = 16. This dose is now being applied in clinical practice.

  5. 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.

  6. 活化蛋白C的研究进展%Advances in research of activated protein C

    Institute of Scientific and Technical Information of China (English)

    陈娅

    2013-01-01

    蛋白C是一种存在于血液中的维生素K依赖性糖蛋白酶,在凝血酶-血栓调节蛋白(T-TM)复合物作用下活化为活化蛋白C(APC).APC是重要的抗凝因子之一,具有抗炎、抗凋亡及保护内皮屏障等作用.研究证实,APC与多种疾病相关,本文重点阐述APC与糖尿病肾病之间的关系.%Protein C ( PC) is a vitamin K-dependent glycoprotein and circulates in plasma. Activated protein C (APC)is generated when thrombin-thrombomodulin complex activates protein C. Besides its important anticoagulant role, APC exerts multiple functions including anti-inflammatory activities, antiapoptotic activity and protection of endothelial barrier effect. A lot of studies revealed that APC was associated with diverse diseases. This review emphasizes the relationship between APC and diabetic nephropathy.

  7. A meta-analysis of controlled trials of recombinant human activated protein C therapy in patients with sepsis

    Directory of Open Access Journals (Sweden)

    Wiedermann Christian J

    2005-10-01

    Full Text Available Abstract Background Meta-analysis of two randomised controlled trials in severe sepsis performed with recombinant human activated protein C may provide further insight as to the therapeutic utility of targeting the clotting cascade in this syndrome. Methods In search for relevant studies published, two randomized clinical trials were found eligible. Results The studies, PROWESS and ADDRESS, enrolled a total of 4329 patients with risk ratio (RR and 95% confidence interval (CI data for effect on 28-day mortality relative to control treatment of 0.92 (0.83–1.02 suggesting that recombinant human activated protein C is not beneficial in severe sepsis. In PROWESS, 873 of 1690 patients presented with low risk, and 2315 of 2639 patients in ADDRESS as defined by APACHE II score Conclusion This meta-analysis, therefore, raises doubts about the clinical usefulness of recombinant activated protein C in patients with severe sepsis and an APACHE II score ≥ 25 which can only be resolved by another properly designed clinical trial.

  8. 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.

  9. 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.

  10. 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.

  11. 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...... two different parameterizations. Detailed comparisons show that the bandwidth of slow light propagation can be significantly enhanced by allowing irregular geometries in the waveguides. To mitigate the propagation loss due to scattering in the photonic crystal waveg- uides, an optimization problem...... is formulated to minimize the average propagation loss of the designed modes. The presented approach is employed to design a free-topology slow light waveguide. Numerical result illustrates that slow light propagation in the optimized waveguide displays significantly suppressed propagation loss while keeping...

  12. 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.

  13. 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.

  14. Inducing Acute Traumatic Coagulopathy In Vitro: The Effects of Activated Protein C on Healthy Human Whole Blood.

    Directory of Open Access Journals (Sweden)

    Benjamin M Howard

    Full Text Available Acute traumatic coagulopathy has been associated with shock and tissue injury, and may be mediated via activation of the protein C pathway. Patients with acute traumatic coagulopathy have prolonged PT and PTT, and decreased activity of factors V and VIII; they are also hypocoagulable by thromboelastometry (ROTEM and other viscoelastic assays. To test the etiology of this phenomenon, we hypothesized that such coagulopathy could be induced in vitro in healthy human blood with the addition of activated protein C (aPC.Whole blood was collected from 20 healthy human subjects, and was "spiked" with increasing concentrations of purified human aPC (control, 75, 300, 2000 ng/mL. PT/PTT, factor activity assays, and ROTEM were performed on each sample. Mixed effect regression modeling was performed to assess the association of aPC concentration with PT/PTT, factor activity, and ROTEM parameters.In all subjects, increasing concentrations of aPC produced ROTEM tracings consistent with traumatic coagulopathy. ROTEM EXTEM parameters differed significantly by aPC concentration, with stepwise prolongation of clotting time (CT and clot formation time (CFT, decreased alpha angle (α, impaired early clot formation (a10 and a20, and reduced maximum clot firmness (MCF. PT and PTT were significantly prolonged at higher aPC concentrations, with corresponding significant decreases in factor V and VIII activity.A phenotype of acute traumatic coagulopathy can be induced in healthy blood by the in vitro addition of aPC alone, as evidenced by viscoelastic measures and confirmed by conventional coagulation assays and factor activity. This may lend further mechanistic insight to the etiology of coagulation abnormalities in trauma, supporting the central role of the protein C pathway. Our findings also represent a model for future investigations in the diagnosis and treatment of acute traumatic coagulopathy.

  15. Immunobiology and therapeutic applications of protein c/protein s/thrombomodulin in human and experimental allotransplantation and xenotransplantation.

    Science.gov (United States)

    Hancock, W W; Bach, F H

    1997-07-01

    Protein C (PC), protein S (PS), and thrombomodulin (TM) constitute a well-established, physiologically important anticoagulant pathway, but they also possess significant antiinflammatory and immunoregulatory properties through their ability to regulate macrophage activation. In vivo and in vitro data concerning these antiinflammatory actions are reviewed, with an emphasis on changes in the levels of these proteins during allograft and xenograft rejection, and potential therapeutic applications arising from their exogenous administration, or genetic engineering to maintain their expression, posttransplantation. (Trends Cardiovasc Med 1997;7:174-183). © 1997, Elsevier Science Inc.

  16. Concurrent administration of heparin and activated protein C in a patient with pulmonary embolism and severe sepsis with positive outcome

    Directory of Open Access Journals (Sweden)

    Juneja Deven

    2009-01-01

    Full Text Available Results of the PROWESS trial suggested that heparin may reduce the efficacy of recombinant human activated protein C (rhAPC and the XPRESS study also showed increased bleeding complications in patients receiving heparin with rhAPC. Although it has been shown that heparin prophylaxis may be used along with rhAPC, no study has shown the interaction between continuous heparin infusion and rhAPC. Here, we report a case of severe sepsis with pulmonary embolism who was concurrently administered heparin and rhAPC infusions, with positive results and no bleeding complications.

  17. Instability of human TATA-binding protein CAG triplet repeats during amplification by PCR.

    Science.gov (United States)

    Holstege, F C; van der Vliet, P C; Timmers, H T

    1994-09-13

    Polymerase chain reaction (PCR) of a TATA-binding protein cDNA that contains CAG triplet repeats results in heterogeneous products. This is caused by a variable loss in the number of CAG triplets. Sequence analysis of PCR products suggests that instability increases with repeat length.

  18. Slow wave propagation in soft adhesive interfaces.

    Science.gov (United States)

    Viswanathan, Koushik; Sundaram, Narayan K; Chandrasekar, Srinivasan

    2016-11-16

    Stick-slip in sliding of soft adhesive surfaces has long been associated with the propagation of Schallamach waves, a type of slow surface wave. Recently it was demonstrated using in situ experiments that two other kinds of slow waves-separation pulses and slip pulses-also mediate stick-slip (Viswanathan et al., Soft Matter, 2016, 12, 5265-5275). While separation pulses, like Schallamach waves, involve local interface detachment, slip pulses are moving stress fronts with no detachment. Here, we present a theoretical analysis of the propagation of these three waves in a linear elastodynamics framework. Different boundary conditions apply depending on whether or not local interface detachment occurs. It is shown that the interface dynamics accompanying slow waves is governed by a system of integral equations. Closed-form analytical expressions are obtained for the interfacial pressure, shear stress, displacements and velocities. Separation pulses and Schallamach waves emerge naturally as wave solutions of the integral equations, with oppositely oriented directions of propagation. Wave propagation is found to be stable in the stress regime where linearized elasticity is a physically valid approximation. Interestingly, the analysis reveals that slow traveling wave solutions are not possible in a Coulomb friction framework for slip pulses. The theory provides a unified picture of stick-slip dynamics and slow wave propagation in adhesive contacts, consistent with experimental observations.

  19. 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 ...

  20. Global Network of Slow Solar Wind

    Science.gov (United States)

    Crooker, N. U.; Antiochos, S. K.; Zhao, X.; Neugebauer, M.

    2012-01-01

    The streamer belt region surrounding the heliospheric current sheet (HCS) is generally treated as the primary or sole source of the slow solar wind. Synoptic maps of solar wind speed predicted by the Wang-Sheeley-Arge model during selected periods of solar cycle 23, however, show many areas of slow wind displaced from the streamer belt. These areas commonly have the form of an arc that is connected to the streamer belt at both ends. The arcs mark the boundaries between fields emanating from different coronal holes of the same polarity and thus trace the paths of belts of pseudostreamers, i.e., unipolar streamers that form over double arcades and lack current sheets. The arc pattern is consistent with the predicted topological mapping of the narrow open corridor or singular separator line that must connect the holes and, thus, consistent with the separatrix-web model of the slow solar wind. Near solar maximum, pseudostreamer belts stray far from the HCS-associated streamer belt and, together with it, form a global-wide web of slow wind. Recognition of pseudostreamer belts as prominent sources of slow wind provides a new template for understanding solar wind stream structure, especially near solar maximum.

  1. Topological Origins of the Slow Solar Wind

    Science.gov (United States)

    Antiochos, S.

    2008-12-01

    Although the slow solar wind has been studied for decades with both in situ and remote sensing observations, its origin is still a matter of intense debate. In the standard quasi-steady model, the slow wind is postulated to originate near coronal hole boundaries that define topologically well-behaved separatrices between open and closed field regions. In the interchange model, on the other hand, the slow wind is postulated to originate on open flux that is dynamically diffusing throughout the seemingly closed-field corona. We argue in favor of the quasi-steady scenario and propose that the slow wind is due to two effects: First, the open-closed boundary is highly complex due to the complexity of the photospheric flux distribution. Second, this boundary is continuously driven by the transport of magnetic helicity from the closed field region into the open. The implications of this model for the structure and dynamics of the corona and slow wind are discussed, and observational tests of the model are presented. This work has been supported, in part, by the NASA LWS, HTP, and SR&T programs.

  2. Acquired Activated Protein C Resistance, Thrombophilia and Adverse Pregnancy Outcomes: A Study Performed in an Irish Cohort of Pregnant Women

    Directory of Open Access Journals (Sweden)

    Sara Sedano-Balbás

    2011-01-01

    Full Text Available The combination of thrombophilia and pregnancy increases the risk of thrombosis and the potential for adverse outcomes during pregnancy. The most significant common inherited risk factor for thrombophilia is activated protein C resistance (APCR, a poor anticoagulant response of APC in haemostasis, which is mainly caused by an inherited single-nucleotide polymorphism (SNP, factor V G1691A (FV Leiden (FVL, referred as inherited APCR. Changes in the levels of coagulation factors: FV, FVIII, and FIX, and anticoagulant factors: protein S (PS and protein C (PC can alter APC function causing acquired APCR. Prothrombin G20210A and methylenetetrahydrofolate reductase (MTHFR C677T are prothrombotic SNPs which in association with APCR can also increase the risk of thrombosis amongst Caucasians. In this study, a correlation between an acquired APCR phenotype and increased levels of factors V, VIII, and IX was demonstrated. Thrombophilic mutations amongst our acquired APCR pregnant women cohort are relatively common but do not appear to exert a severe undue adverse effect on pregnancy.

  3. Optical slowing of calcium monofluoride molecules

    Science.gov (United States)

    Ravi, Aakash; Chae, Eunmi; Hemmerling, Boerge; Anderegg, Loic; Augenbraun, Benjamin; Drayna, Garrett; Hutzler, Nicholas; Collopy, Alejandra; Wu, Yewei; Ding, Shiqian; Ye, Jun; Ketterle, Wolfgang; Doyle, John

    2016-05-01

    We report white-light slowing of calcium monofluoride molecules. A single main laser (606 nm) plus two additional vibrational repump lasers (628 nm) are employed. The slowing lasers are spectrally broadened to address the molecules' velocity spread and hyperfine splittings. We use a background-free two-photon fluorescence detection scheme to make high signal-to-noise measurements of our molecular beam's longitudinal velocity distribution. This method is applied to slow CaF produced by a two-stage cryogenic buffer gas beam source by > 30 m/s to near the capture velocity of a molecular magneto-optical trap (MOT). Due to the presence of magnetic dark states which inhibit optical cycling, we will use an AC-MOT. We characterize the performance of this AC-MOT used in the trapping of Li and Yb.

  4. Universality of slow decorrelation in KPZ growth

    CERN Document Server

    Corwin, I; Peche, S

    2010-01-01

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

  5. 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.

  6. Synchronized ion acceleration by ultraintense slow light

    CERN Document Server

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

    2015-01-01

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

  7. Ultrafast Faraday Rotation of Slow Light

    Science.gov (United States)

    Musorin, A. I.; Sharipova, M. I.; Dolgova, T. V.; Inoue, M.; Fedyanin, A. A.

    2016-08-01

    The active control of optical signals in the time domain is what science and technology demand in fast all-optical information processing. Nanostructured materials can modify the group velocity and slow the light down, as the artificial light dispersion emerges. We observe the ultrafast temporal behavior of the Faraday rotation within a single femtosecond laser pulse under conditions of slow light in a one-dimensional magnetophotonic crystal. The Faraday effect changes by 20% over the time of 150 fs. This might be applicable to the fast control of light in high-capacity photonic devices.

  8. Geodynamic environments of ultra-slow spreading

    Science.gov (United States)

    Kokhan, Andrey; Dubinin, Evgeny

    2015-04-01

    Ultra-slow spreading is clearly distinguished as an outstanding type of crustal accretion by recent studies. Spreading ridges with ultra-slow velocities of extension are studied rather well. But ultra-slow spreading is characteristic feature of not only spreading ridges, it can be observed also on convergent and transform plate boundaries. Ultra-slow spreading is observed now or could have been observed in the past in the following geodynamic environments on divergent plate boundaries: 1. On spreading ridges with ultra-slow spreading, both modern (f.e. Gakkel, South-West Indian, Aden spreading center) and ceased (Labrador spreading center, Aegir ridge); 2. During transition from continental rifting to early stages of oceanic spreading (all spreading ridges during incipient stages of their formation); 3. During incipient stages of formation of spreading ridges on oceanic crust as a result of ridge jumps and reorganization of plate boundaries (f.e. Mathematicians rise and East Pacific rise); 4. During propagation of spreading ridge into the continental crust under influence of hotspot (Aden spreading center and Afar triple junction), under presence of strike-slip faults preceding propagation (possibly, rift zone of California Bay). Ultra-slow spreading is observed now or could have been observed in the past in the following geodynamic environments on transform plate boundaries: 1. In transit zones between two "typical" spreading ridges (f.e. Knipovich ridge); 2. In semi strike-slip/extension zones on the oceanic crust (f.e. American-Antarctic ridge); 3. In the zones of local extension in regional strike-slip areas in pull-apart basins along transform boundaries (Cayman trough, pull-apart basins of the southern border of Scotia plate). Ultra-slow spreading is observed now or could have been observed in the past in the following geodynamic environments on convergent plate boundaries: 1. During back-arc rifting on the stage of transition into back-arc spreading (central

  9. 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.

  10. A slow gravity compensated atom laser

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  11. Proton energy dependence of slow neutron intensity

    Energy Technology Data Exchange (ETDEWEB)

    Teshigawara, Makoto; Harada, Masahide; Watanabe, Noboru; Kai, Tetsuya; Sakata, Hideaki; Ikeda, Yujiro [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment; Ooi, Motoki [Hokkaido Univ., Sapporo (Japan)

    2001-03-01

    The choice of the proton energy is an important issue for the design of an intense-pulsed-spallation source. The optimal proton beam energy is rather unique from a viewpoint of the leakage neutron intensity but no yet clear from the slow-neutron intensity view point. It also depends on an accelerator type. Since it is also important to know the proton energy dependence of slow-neutrons from the moderators in a realistic target-moderator-reflector assembly (TMRA). We studied on the TMRA proposed for Japan Spallation Neutron Source. The slow-neutron intensities from the moderators per unit proton beam power (MW) exhibit the maximum at about 1-2 GeV. At higher proton energies the intensity per MW goes down; at 3 and 50 GeV about 0.91 and 0.47 times as low as that at 1 GeV. The proton energy dependence of slow-neutron intensities was found to be almost the same as that of total neutron yield (leakage neutrons) from the same bare target. It was also found that proton energy dependence was almost the same for the coupled and decoupled moderators, regardless the different moderator type, geometry and coupling scheme. (author)

  12. Moving Crystal Slow-Neutron Wavelength Analyser

    DEFF Research Database (Denmark)

    Buras, B.; Kjems, Jørgen

    1973-01-01

    Experimental proof that a moving single crystal can serve as a slow-neutron wavelength analyser of special features is presented. When the crystal moves with a velocity h/(2 md) (h-Planck constant, m-neutron mass, d-interplanar spacing) perpendicular to the diffracting plane and the analysed...

  13. Where does slow axonal transport go?

    Science.gov (United States)

    Terada, Sumio

    2003-12-01

    Axonal transport is the specialized and well-developed intracellular transport system for regulated and/or long-distance transport based on generalized cellular machineries. Among them, slow axonal transport conveys cytoplasmic proteins. The motor molecule, the nature of transporting complex and the transport regulation mechanism for slow transport are still unclarified. There has been a dispute regarding the nature of transporting complex of cytoskeletal proteins, polymer-sliding hypothesis versus subunit-transport theory. Recent data supporting the hypothesis of polymer sliding in cultured neurons only reconfirm the previously reported structure and this inference suffers from the lack of ultrastructural evidence and the direct relevance to the physiological slow transport phenomenon in vivo. Observation of the moving cytoskeletal proteins in vivo using transgenic mice or squid giant axons revealed that subunits do move in a microtubule-dependent manner, strongly indicating the involvement of microtubule-based motor kinesin. If the slow transport rate reflects the intermittent fast transport dependent on kinesin motor, we have to investigate the molecular constituents of the transporting complex in more detail and evaluate why the motor and cargo interaction is so unstable. This kind of weak and fluctuating interaction between various molecular pairs could not be detected by conventional techniques, thus necessitating the establishment of a new experimental system before approaching the molecular regulation problem.

  14. Origin of pseudotachylites during slow creep experiments

    NARCIS (Netherlands)

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

    2012-01-01

    We conducted a series of experiments on granitoid cataclasites under mid-crustal conditions (Pc∼500 MPa, T=300 °C) and slow displacement rates (10−8 ms−1

  15. Exploring the Hedonic Quality of Slow Technology

    OpenAIRE

    Orehovački, Tihomir; Al Sokkar, Abdullah A.M.; Derboven, Jan; Khan, Azam

    2013-01-01

    Pace is an inseparable part of all technologies and consequently represents an interaction design element. Various technology aspects can support hedonic qualities brought about from reflection transformed into unlimited unique experiences, mental rest, and inner peace. This paper argues different approaches to technology pace evaluation. Attributes that contribute to the hedonic quality of slow technology are presented and discussed.

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

    Science.gov (United States)

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

    2011-01-01

    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 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, while 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 largely 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 as compared to ketamine-xylazine anesthesia. PMID:22016533

  17. 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.

  18. Detecting the form of selection in the outer membrane protein C of Enterobacter aerogenes strains and Salmonella species.

    Science.gov (United States)

    Padhi, Abinash; Verghese, Bindhu; Otta, Subhendu K

    2009-01-01

    The types of selective pressure operating on the outer membrane protein C (ompC) of Enterobacter aerogenes strains, the causative agent for nosocomial infections, and Salmonella sp., the hazardous pathogen are investigated using the maximum likelihood-based codon substitution models. Although the rate of amino acid replacement to the silent substitution (omega) across the entire codon sites of ompC of E. aerogenes (omega=0.3194) and Salmonella sp. (omega=0.2047) indicate that the gene is subjected to purifying selection (i.e. omega1). Such contrast in the intensity of selective pressures in both pathogens could be associated with the differential response to the adverse environmental changes. In E. aerogenes, majority of the positively selected sites are located in the hypervariable cell-surface-exposed domains whereas the trans-membrane domains are functionally highly constrained.

  19. 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.

  20. Large Left Ventricular Thrombus in a Patient with Systemic and Venous Thromboembolism Secondary to Protein C and S Deficiency

    Science.gov (United States)

    Ainapurapu, Bujji

    2017-01-01

    58-year-old Hispanic female presented with an altered mental status. A CT scan of the head demonstrated multiple scattered infarcts and a large right temporal lobe infarct. We also diagnosed the patient with right popliteal and femoral vein thrombosis, bilateral pulmonary embolism, and a transient right radial artery occlusion. Her 12-lead EKG showed lateral ST elevation. Emergent coronary angiogram revealed normal coronaries. Echocardiogram demonstrated a large mobile mass attached to the anterolateral free wall with overall normal contractility of the left ventricle. The patient underwent surgical embolectomy to prevent further systemic embolization. Coagulability workup returned positive for protein C and S deficiency. The patient did well after surgery. Following her surgery, we initiated chronic oral anticoagulation. The presentation with intracardiac thrombus in a normal heart should raise a concern of a probable thrombophilia. PMID:28133551

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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...

  10. Eldor spin echoes and slow motions

    Science.gov (United States)

    Hornak, Joseph P.; Freed, Jack H.

    1983-10-01

    It is shown how an ELDOR technique based upon spin echoes and rapid stepping of the magnetic field may be employed to measure rotational correlation times, τ R for very slow motions. Experiments on PD-Tempone in 85% glycerol/ D 2O at low temperatures led to τ R values of 10 -4 to 10 -5 s obtained with a simple analysis of the data.

  11. MIND diet slows cognitive decline with aging

    OpenAIRE

    Morris, Martha Clare; Tangney, Christy C.; Wang, Yamin; Sacks, Frank Martin; Barnes, Lisa L.; Bennett, David William; Aggarwal, Neelum T

    2015-01-01

    INTRODUCTION: The Mediterranean and dash diets have been shown to slow cognitive decline; however, neither diet is specific to the nutrition literature on dementia prevention. METHODS: We devised the Mediterranean-Dietary Approach to Systolic Hypertension (DASH) diet intervention for neurodegenerative delay (MIND) diet score that specifically captures dietary components shown to be neuroprotective and related it to change in cognition over an average 4.7 years among 960 participants ...

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. Analysis of coagulation tests, proteins C and S, and plasma fibrinogen in addicts and non-addicts with coronary artery disease

    Directory of Open Access Journals (Sweden)

    Abdolrasoul Moloudi

    2014-03-01

    Full Text Available Given the high incidence of drug addiction in the society and high prevalence of Coronary Artery Disease (CAD in opium users, this study was conducted to evaluate the coagulation tests and plasma levels of proteins C and S, and fibrinogen in opium users with Coronary Artery Disease (CAD. The results indicated that the plasma level of fibrinogen in addicted patients was higher than that of non-addicted patients (p=0.001, but the findings of coagulation tests and proteins C and S levels revealed no significant difference between groups.

  18. 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.

  19. Occurrence of complement protein C3 in dying pyramidal neurons in rat hippocampus after systemic administration of kainic acid.

    Science.gov (United States)

    Morita, Hiroyuki; Suzuki, Katsuaki; Mori, Norio; Yasuhara, Osamu

    2006-11-27

    To evaluate the roles of complement in kainic acid (KA)-induced neuronal damages, the immunohistochemical localization of the complement protein C3 was examined in rat hippocampus after systemic KA injection. The immunoreactivity for C3 was found in glial cells in control rats, and such glial cells were increased in number after KA injection. Our confocal study showed that C3-positive glial cells were microglia. Three to seven days after KA, C3 immunoreactivity appeared in CA1 and CA3 pyramidal neurons. Double staining for C3 combined with the terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling showed that occurrence of C3 immunoreactivity in neurons coincided well with that of DNA fragmentation. Western blot analysis and RT-PCR experiments suggested local synthesis of C3 by brain cells. Our results suggest that C3 contributes greatly to neuronal death after systemic KA administration, and that microglia and neurons are the local source of C3 in KA-induced brain injury.

  20. 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.

  1. Down-regulation of endothelial protein C receptor shedding by persicarin and isorhamnetin-3-O-galactoside.

    Science.gov (United States)

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

    2013-07-01

    Increasing evidence has shown that beyond its role in coagulation, endothelial protein C receptor (EPCR) plays an important role in the cytoprotective pathway. Previous reports have shown that EPCR can be shed from the cell surface, and that this is mediated by tumor necrosis factor-α converting enzyme (TACE) and that sEPCR levels are increased in patients with systemic inflammatory diseases. Persicarin and isorhamnetin-3-O-galactoside (I3G) are active compounds from Oenanthe javanica, which has been widely studied for its neuroprotective, antioxidant, and barrier protective activities. However, little is known of the effects of persicarin on EPCR shedding. Here, we investigated this issue by monitoring the effects of persicarin and I3G on phorbol-12-myristate 13-acetate (PMA) and on cecal ligation and puncture (CLP)-mediated EPCR shedding and underlying mechanisms. According to the results, persicarin and I3G induced potent inhibition of PMA and CLP-induced EPCR shedding by suppressing expression of TACE. In addition, persicarin and I3G reduced PMA-stimulated phosphorylation of p38MAPK, extracellular regulated kinases (ERK) 1/2, and c-Jun N-terminal kinase (JNK). Given these results, persicarin and I3G could be used as a candidate therapeutic for treatment of severe vascular inflammatory diseases.

  2. 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.

  3. An accompanying genetic severe deficiency of tissue factor protects mice with a protein C deficiency from lethal endotoxemia.

    Science.gov (United States)

    Castellino, Francis J; Donahue, Deborah L; Navari, Rudolph M; Ploplis, Victoria A; Walsh, Mark

    2011-01-06

    Mice with a severe genetic deficiency of protein C (PC), PC(-/-)PC(tg4), display enhanced susceptibility to lethal effects of gram-negative endotoxemia induced by lipopolysaccharide (LPS), whereas mice severely deficient in tissue factor (TF), TF(-/-)hTF(tg), are protected from LPS-mediated lethality. In this study, we show that a simultaneous severe deficiency of TF protected low-PC mice from LPS-induced death, resulting in a survival profile similar to that experienced by wild-type (WT) mice. Plasma and whole blood coagulation assays, the latter measured by thromboelastography, demonstrated development of coagulopathies in LPS-treated mice, which were more severe in the case of the doubly deficient TF(-/-)hTF(tg)/PC(-/-)PC(tg4) mice, mainly reflecting earlier signs of disseminated intravascular coagulation in this latter cohort. Markers of inflammation were also elevated in response to LPS in both groups of mice at times just preceding death. We conclude that whereas coagulopathies are more exacerbated in LPS-treated TF(-/-)hTF(tg)/PC(-/-)PC(tg4) mice, the lowering of TF levels in mice with an accompanying severe PC deficiency confers protection against death compared with mice with a single severe PC deficiency. This suggests that proteases generated as a result of factor VIIa/TF-mediated thrombin generation play a mechanistic role in the enhanced lethality seen under very low PC conditions in an endotoxemia model in mice.

  4. 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.

  5. 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 <50%; all received PC concentrate (Ceprotin(®), Baxter) for 72 hr in adjusted doses to restore normal PC values (70-120%). Blood 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.

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

    Directory of Open Access Journals (Sweden)

    Jong-Sup Bae

    2013-11-01

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

  7. The protein C activity and cytochrome P4502C19 (CYP2C19) gene expression in the patients with acute deep vein thrombosis (DVT)%遗传因素蛋白C活性与CYP2C19基因在DVT患者血清中的表达及其意义

    Institute of Scientific and Technical Information of China (English)

    周瑜; 张明; 乔彤

    2013-01-01

    目的:研究急性深静脉血栓(DVT)患者外周血中蛋白C活性,及细胞色素P4502C19(CYP2C19)基因表达情况,探讨在DVT患者中蛋白C系统与CYP2C19表达之间的关系,了解这两种遗传性因素在DVT患者发病过程中所起作用及其重要性。方法检测213例DVT患者外周血蛋白C活性及CYP2C19基因表达,掌握遗传性蛋白C缺陷症、CYP2C19基因突变对DVT发病影响及重要性。结果与126例对照组相比,骨折、外伤、其他手术史的DVT组的患者蛋白C活性原发性降低,差异具有统计学意义(P<0.05);CYP2C19基因变异型(中间代谢、慢代谢型)分布未见明显特点,差异无统计学意义。结论遗传性蛋白C缺陷对DVT发病起重要作用, CYP2C19基因对于DVT患者的治疗预后关系密切,但对于DVT发病作用未见明显特征。而蛋白C与CYP2C19基因表达在DVT患者中未见明显关联。%Objective To explore the protein C activity and cytochrome P4502C19 (CYP2C19) gene expression in the patients with acute deep vein thrombosis (DVT) to determine the relationship of these two genetic factors( protein C system and the expression of CYP2C19 ) with DVT and to study the role and importance on these both genetic factors in the pathogenesis of patients with DVT. Methods The protein C activity and expression of CYP2C19 gene were detected in 213 cases of DVT patients so as to mastering the hereditary protein C deficiency, CYP2C19 gene mutation affecting to the incidence and significance of DVT. Results The protein C activity decreased in the group of the patients with DVT with fractures, trauma, and surgical history primary decreased protein C activity compared with control group of 126 cases. The difference is statistically significant between two groups(P< 0.05). CYP2C19 gene variant including intermediary metabolism and slow metabolism had no significant distribution characteristic.The difference was not statistically

  8. 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].

  9. 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.

  10. Lead Slowing Down Spectrometer Status Report

    Energy Technology Data Exchange (ETDEWEB)

    Warren, Glen A.; Anderson, Kevin K.; Bonebrake, Eric; Casella, Andrew M.; Danon, Yaron; Devlin, M.; Gavron, Victor A.; Haight, R. C.; Imel, G. R.; Kulisek, Jonathan A.; O' Donnell, J. M.; Weltz, Adam

    2012-06-07

    This report documents the progress that has been completed in the first half of FY2012 in the MPACT-funded Lead Slowing Down Spectrometer project. Significant progress has been made on the algorithm development. We have an improve understanding of the experimental responses in LSDS for fuel-related material. The calibration of the ultra-depleted uranium foils was completed, but the results are inconsistent from measurement to measurement. Future work includes developing a conceptual model of an LSDS system to assay plutonium in used fuel, improving agreement between simulations and measurement, design of a thorium fission chamber, and evaluation of additional detector techniques.

  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....

  12. 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...

  13. 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...

  14. 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.

  15. Liquid crystal light valves for slow light and applications

    Energy Technology Data Exchange (ETDEWEB)

    Residori, S; Bortolozzo, U [INLN, CNRS, University de Nice Sophia-Antipolis, 1361 route des Lucioles, 06560 Valbonne (France); Huignard, J P, E-mail: jean-pierre.huignard@thalesgroup.co [Thales Research and Technology, RD 128 91767, Palaiseau Cedex (France)

    2010-02-01

    The large dispersive properties of wave mixing in liquid crystal light-valves allow obtaining fast and slow light with tunable group velocities. A slow light interferometer is shown by using this interaction.

  16. Syntaxin 1A binds to the cytoplasmic C terminus of Kv2.1 to regulate channel gating and trafficking.

    Science.gov (United States)

    Leung, Yuk M; Kang, Youhou; Gao, Xiaodong; Xia, Fuzhen; Xie, Huanli; Sheu, Laura; Tsuk, Sharon; Lotan, Ilana; Tsushima, Robert G; Gaisano, Herbert Y

    2003-05-09

    Voltage-gated K(+) (Kv) 2.1 is the dominant Kv channel that controls membrane repolarization in rat islet beta-cells and downstream insulin exocytosis. We recently showed that exocytotic SNARE protein SNAP-25 directly binds and modulates rat islet beta-cell Kv 2.1 channel protein at the cytoplasmic N terminus. We now show that SNARE protein syntaxin 1A (Syn-1A) binds and modulates rat islet beta-cell Kv2.1 at its cytoplasmic C terminus (Kv2.1C). In HEK293 cells overexpressing Kv2.1, we observed identical effects of channel inhibition by dialyzed GST-Syn-1A, which could be blocked by Kv2.1C domain proteins (C1: amino acids 412-633, C2: amino acids 634-853), but not the Kv2.1 cytoplasmic N terminus (amino acids 1-182). This was confirmed by direct binding of GST-Syn-1A to the Kv2.1C1 and C2 domains proteins. These findings are in contrast to our recent report showing that Syn-1A binds and modulates the cytoplasmic N terminus of neuronal Kv1.1 and not by its C terminus. Co-expression of Syn-1A in Kv2.1-expressing HEK293 cells inhibited Kv2.1 surfacing, which caused a reduction of Kv2.1 current density. In addition, Syn-1A caused a slowing of Kv2.1 current activation and reduction in the slope factor of steady-state inactivation, but had no affect on inactivation kinetics or voltage dependence of activation. Taken together, SNAP-25 and Syn-1A mediate secretion not only through its participation in the exocytotic SNARE complex, but also by regulating membrane potential and calcium entry through their interaction with Kv and Ca(2+) channels. In contrast to Ca(2+) channels, where these SNARE proteins act on a common synprint site, the SNARE proteins act not only on distinct sites within a Kv channel, but also on distinct sites between different Kv channel families.

  17. 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...

  18. 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....

  19. 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.

  20. Slow Photons for Photocatalysis and Photovoltaics.

    Science.gov (United States)

    Liu, Jing; Zhao, Heng; Wu, Min; Van der Schueren, Benoit; Li, Yu; Deparis, Olivier; Ye, Jinhua; Ozin, Geoffrey A; Hasan, Tawfique; Su, Bao-Lian

    2017-02-06

    Solar light is widely recognized as one of the most valuable renewable energy sources for the future. However, the development of solar-energy technologies is severely hindered by poor energy-conversion efficiencies due to low optical-absorption coefficients and low quantum-conversion yield of current-generation materials. Huge efforts have been devoted to investigating new strategies to improve the utilization of solar energy. Different chemical and physical strategies have been used to extend the spectral range or increase the conversion efficiency of materials, leading to very promising results. However, these methods have now begun to reach their limits. What is therefore the next big concept that could efficiently be used to enhance light harvesting? Despite its discovery many years ago, with the potential for becoming a powerful tool for enhanced light harvesting, the slow-photon effect, a manifestation of light-propagation control due to photonic structures, has largely been overlooked. This review presents theoretical as well as experimental progress on this effect, revealing that the photoreactivity of materials can be dramatically enhanced by exploiting slow photons. It is predicted that successful implementation of this strategy may open a very promising avenue for a broad spectrum of light-energy-conversion technologies.

  1. 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.

  2. 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…

  3. 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...

  4. Automated classification of spatiotemporal characteristics of gastric slow wave propagation.

    Science.gov (United States)

    Paskaranandavadivel, Niranchan; Gao, Jerry; Du, Peng; O'Grady, Gregory; Cheng, Leo K

    2013-01-01

    Gastric contractions are underpinned by an electrical event called slow wave activity. High-resolution electrical mapping has recently been adapted to study gastric slow waves at a high spatiotemporal detail. As more slow wave data becomes available, it is becoming evident that the spatial organization of slow wave plays a key role in the initiation and maintenance of gastric dsyrhythmias in major gastric motility disorders. All of the existing slow wave signal processing techniques deal with the identification and partitioning of recorded wave events, but not the analysis of the slow wave spatial organization, which is currently performed visually. This manual analysis is time consuming and is prone to observer bias and error. We present an automated approach to classify spatial slow wave propagation patterns via the use of Pearson cross correlations. Slow wave propagations were grouped into classes based on their similarity to each other. The method was applied to high-resolution gastric slow wave recordings from four pigs. There were significant changes in the velocity of the gastric slow wave wavefront and the amplitude of the slow wave event when there was a change in direction to the slow wave wavefront during dsyrhythmias, which could be detected with the automated approach.

  5. Characterization of the interaction between human complement protein C4 and a single-chain variable fragment antibody by capillary electrophoresis and surface plasmon resonance

    NARCIS (Netherlands)

    Seifar, R.M.; Cool, Robbert; Quax, Wim; Bischoff, Rainer

    2004-01-01

    Immunoaffinity capillary electrophoresis and surface plasmon resonance have been used for the characterization of the interaction between two large-sized proteins, the human complement protein C4 and the single-chain variable fragment C43. The rather high kinetic rate constants as determined by surf

  6. 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.

  7. 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...

  8. Effects of activated protein C on coagulation and fibrinolysis in rabbits with endotoxin induced acute lung injury

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Background Sepsis induced acute lung injury (ALl) as a common syndrome in clinical practice has a high mortality. Recombinant human activated protein C (APC) can significantly reduce the mortality of patients with severe sepsis. Several studies have implicated that APC may be protective in ALl. Methods Twenty-one rabbits were operatively prepared and randomly divided into sham, control, or APC groups (n=7 in each group). After a tracheotomy had been performed, ALl was produced in the control and APC groups by infusion of Escherichia coli endotoxin 100 pg/kg per hour intravenously for 1 hour. The sham group received only the vehicle, infusion of 20 ml of 0.9% saline. The rabbits were studied under anesthesia for 6 hours and were ventilated with 40% and lasted for 4 hours. The animals were resuscitated with Ringer's lactate solution. Results In comparison with nontreatment in the control group, the infusion of APC significantly reduced the increase of thrombomodulin level (TM; control group was (0.68±0.06) ng/ml, vs APC group of (0.62±0.07) ng/ml at 6 hours, P<0.05), and significantly attenuated the fall in protein S (PS; control group was (2.32±0.03) μg/ml at 2 hours, (2.24±0.06) μg/ml at 4 hours and (2.21±0.09) μg/ml at 6 hours, vs APC group (2.46±0.04) μg/ml at 2 hours, (2.40±0.05) pg/ml at 4 hours and (2.39±0.07) μg/ml at 6 hours, P<0.01). In addition, APC limited the increase in plasminogen activator inhibitor-1 (PAl-1) both in plasma (control group was (0.68±0.12) ng/ml at 1 hour, (0.84±0.06) ng/ml at 2 hours, (0.87±0.08) ng/ml at 4 hours and (0.91±0.05) ng/ml at 6 hours, vs APC group (0.42±0.16) ng/ml at 1 hour, (0.43±0.04) ng/ml at 2 hours, (0.45±0.09) ng/ml at 4 hours and (0.45±0.14) ng/ml at 6 hours, P<0.01) and in bronchoalveolar lavage fluid (at 6 hours: sham, (1.05±0.05) ng/ml; control, (1.13±0.06) ng/ml; APC, (1.06±0.06) ng/ml; P<0.05). However, APC failed to prevent the decrease in PaO/FiO ratio. APC-treated rabbits

  9. 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.

  10. 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.

  11. 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.

  12. Plasma Thrombin Generation and Sensitivity to Activated Protein C Among Patients With Myeloma and Monoclonal Gammopathy of Undetermined Significance.

    Science.gov (United States)

    Crowley, Maeve P; Kevane, Barry; O'Shea, Susan I; Quinn, Shane; Egan, Karl; Gilligan, Oonagh M; Ní Áinle, Fionnuala

    2016-09-01

    The etiology of the prothrombotic state in myeloma has yet to be definitively characterized. Similarly, while recent evidence suggests that patients with monoclonal gammopathy of undetermined significance (MGUS) may also be at increased risk of thrombosis, the magnitude and the etiology of this risk have also yet to be defined. The present study aims to characterize patterns of plasma thrombin generation and sensitivity to the anticoagulant activity of activated protein C (APC) at the time of initial diagnosis of myeloma and in response to therapy in comparison to that observed among patients with MGUS and matched, healthy volunteers. Patients presenting with newly diagnosed/newly relapsed myeloma (n = 8), MGUS (n = 8), and matched healthy volunteers (n = 8) were recruited. Plasma thrombin generation was determined by calibrated automated thrombography. Peak thrombin generation was significantly higher in patients with myeloma (383.4 ± 33.4 nmol/L) and MGUS (353.4 ± 16.5 nmol/L) compared to healthy volunteers (276.7 ± 20.8 nmol/L; P < .05). In the presence of APC, endogenous thrombin potential was significantly lower in control plasma (228.6 ± 44.5 nmol/L × min) than in either myeloma (866.2 ± 241.3 nmol/L × min, P = .01) or MGUS plasma (627 ± 91.5 nmol/L × min, P = .003). Within the myeloma cohort, peak thrombin generation was significantly higher at diagnosis (353.2 ± 15.9 nmol/L) than following completion of the third cycle of therapy (282.1 ± 15.2 nmol/L; P < .005). Moreover, sensitivity to APC increased progressively with each cycle of chemotherapy. Further study of the etiology and evolving patterns of hypercoagulability among patients with these conditions is warranted and may have future implications for thromboprophylaxis strategies.

  13. The Effect of Membrane Environment on Surfactant Protein C Stability Studied by Constant-pH Molecular Dynamics.

    Science.gov (United States)

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

    2015-10-26

    Pulmonary surfactant protein C (SP-C) is a small peptide with two covalently linked fatty acyl chains that plays a crucial role in the formation and stabilization of the pulmonary surfactant reservoirs during the compression and expansion steps of the respiratory cycle. Although its function is known to be tightly related to its highly hydrophobic character and key interactions maintained with specific lipid components, much is left to understand about its molecular mechanism of action. Also, although it adopts a mainly helical structure while associated with the membrane, factors as pH variation and deacylation have been shown to affect its stability and function. In this work, the conformational behavior of both the acylated and deacylated SP-C isoforms was studied in a DPPC bilayer under different pH conditions using constant-pH molecular dynamics simulations. Our findings show that both protein isoforms are remarkably stable over the studied pH range, even though the acylated isoform exhibits a labile helix-turn-helix motif rarely observed in the other isoform. We estimate similar tilt angles for the two isoforms over the studied pH range, with a generally higher degree of internalization of the basic N-terminal residues in the deacylated case, and observe and discuss some protonation-conformation coupling effects. Both isoforms establish contacts with the surrounding lipid molecules (preferentially with the sn-2 ester bonds) and have a local effect on the conformational behavior of the surrounding lipid molecules, the latter being more pronounced for acylated SP-C.

  14. 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

  15. 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…

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

    Directory of Open Access Journals (Sweden)

    Silvia Nozza

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

  17. Slow light pulse propagation in dispersive media

    DEFF Research Database (Denmark)

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

    2009-01-01

    We present a theoretical and numerical analysis of pulse propagation in a semiconductor photonic crystal waveguide with embedded quantum dots in a regime where the pulse is subjected to both waveguide and material dispersion. The group index and the transmission are investigated by finite......-difference-time-domain Maxwell-Bloch simulations and compared to analytic results. For long pulses the group index (transmission) for the combined system is significantly enhanced (reduced) relative to slow light based on purely material or waveguide dispersion. Shorter pulses are strongly distorted and depending on parameters...... broadening or break-up of the pulse may be observed. The transition from linear to nonlinear pulse propagation is quantified in terms of the spectral width of the pulse. To cite this article: T.R. Nielsen et al., C. R. Physique 10 (2009). (C) 2009 Academie des sciences. Published by Elsevier Masson SAS. All...

  18. Limits of slow light in photonic crystals

    DEFF Research Database (Denmark)

    Pedersen, Jesper Goor; Xiao, Sanshui; Mortensen, N. Asger

    2008-01-01

    in the group velocity acquiring a finite value above zero at the band-gap edges while attaining uperluminal values within the band gap. Simple scalings of the minimum and maximum group velocities with the imaginary part of the dielectric function or, equivalently, the linewidth of the broadened states......While ideal photonic crystals would support modes with a vanishing group velocity, state-of-the-art structures have still only provided a slow down by roughly two orders of magnitude. We find that the induced density of states caused by lifetime broadening of the electromagnetic modes results...... are presented. The results obtained are entirely general and may be applied to any effect which results in a broadening of the electromagnetic states, such as loss, disorder, and finite-size effects. This significantly limits the reduction in group velocity attainable via photonic crystals....

  19. Thermal slow evolution of compact objects

    CERN Document Server

    Becerra, L; Nunez, L A

    2013-01-01

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

  20. Slow photon delay and the neutrino velocity

    CERN Document Server

    Gonzalez-Martin, Gustavo R

    2011-01-01

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

  1. 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.

  2. Slow spin relaxation in dipolar spin ice.

    Science.gov (United States)

    Orendac, Martin; Sedlakova, Lucia; Orendacova, Alzbeta; Vrabel, Peter; Feher, Alexander; Pajerowski, Daniel M.; Cohen, Justin D.; Meisel, Mark W.; Shirai, Masae; Bramwell, Steven T.

    2009-03-01

    Spin relaxation in dipolar spin ice Dy2Ti2O7 and Ho2Ti2O7 was investigated using the magnetocaloric effect and susceptibility. The magnetocaloric behavior of Dy2Ti2O7 at temperatures where the orientation of spins is governed by ``ice rules`` (T Tice) revealed thermally activated relaxation; however, the resulting temperature dependence of the relaxation time is more complicated than anticipated by a mere extrapolation of the corresponding high temperature data [1]. A susceptibility study of Ho2Ti2O7 was performed at T > Tice and in high magnetic fields, and the results suggest a slow relaxation of spins analogous to the behavior reported in a highly polarized cooperative paramagnet [2]. [1] J. Snyder et al., Phys. Rev. Lett. 91 (2003) 107201. [2] B. G. Ueland et al., Phys. Rev. Lett. 96 (2006) 027216.

  3. 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.

  4. Computer analysis of slow vital capacity spirograms.

    Science.gov (United States)

    Primiano, F P; Bacevice, A E; Lough, M D; Doershuk, C F

    1982-01-01

    We have developed a digital computer program which evaluates the vital capacity and its subdivisions, expiratory reserve volume and inspiratory capacity. The algorithm examines the multibreath spirogram, a continuous record of quiet breathing interspersed among repeated slow, large volume maneuvers. Quiet breaths are recognized by comparing features of each breath to the respective average and variation of these features for all breaths. A self-scaling, iterative procedure is used to identify those end-tidal points that most likely represent the subject's functional residual capacity. A least-squared error baseline is then fit through these points to partition the vital capacity. Twenty-three spirograms from patients with documented pulmonary disease were independently analyzed by the computer, a pulmonary function technician, and the laboratory supervisor. No practical differences were found among the results. However, the computer's values, in contrast to those of the technician, were reproducible on repeated trials and free of computational and transcriptional errors.

  5. 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.

  6. 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...

  7. A peptide-binding assay for the disease-associated HLA-DQ8 molecule

    DEFF Research Database (Denmark)

    Straumfors, A; Johansen, B H; Vartdal, F;

    1998-01-01

    . The Ha 255-271(Y) peptide bound to DQ8 in a pH-dependent fashion showing optimal binding around pH 5. The association kinetics were relatively slow and the resulting complexes were heat labile. The specificity of peptide binding to DQ8 was investigated in competitive inhibition experiments with a panel...

  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. Fast-slow analysis for parametrically and externally excited systems with two slow rationally related excitation frequencies.

    Science.gov (United States)

    Han, Xiujing; Bi, Qinsheng; Ji, Peng; Kurths, Jürgen

    2015-07-01

    We present a general method for analyzing mixed-mode oscillations (MMOs) in parametrically and externally excited systems with two low excitation frequencies (PEESTLEFs) for the case of arbitrary m:n relation between the slow frequencies of excitations. The validity of the approach has been demonstrated using the equations of Duffing and van der Pol, separately. Our study shows that, by introducing a slow variable and finding the relation between the slow variable and the slow excitations, PEESTLEFs can be transformed into a fast-slow form with a single slow variable and therefore MMOs observed in PEESTLEFs can be understood by the classical machinery of fast subsystem analysis of the transformed fast-slow system.

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

    Science.gov (United States)

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

    2002-11-01

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

  11. 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.

  12. 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.

  13. Wall mode stabilization at slow plasma rotation

    Science.gov (United States)

    Hu, Bo; Betti, Riccardo; Reimerdes, Holger; Garofalo, Andrea; Manickam, Janardhan

    2007-11-01

    Unstable pressure-driven external kink modes, which become slowly growing resistive wall modes (RWMs) in the presence of a resistive wall, can lead to tokamak plasma disruptions at high beta. It has been shown that RWMs are stabilized by fast plasma rotation (about 1-2% of the Alfv'en frequency) in experiments. Conventional theories attribute the RWM suppression to the dissipation induced by the resonances between plasma rotation and ion bounce/transit or shear Alfv'en frequencies [1]. In those theories, the kinetic effects associated with the plasma diamagnetic frequencies and trapped-particle precession drift frequencies are neglected. It has been observed in recent experiments [2,3] that the RWM suppression also occurs at very slow plasma rotation (about 0.3% of the Alfv'en frequency), where the conventional dissipation is too small to fully suppress the RWMs. Here it is shown, that the trapped-particle kinetic contribution associated with the precession motion [4] is large enough to stabilize the RWM in DIII-D at low rotation. Work supported by the US-DoE OFES. [1] A. Bondeson and M. S. Chu, Physics of Plasmas, 3,3013 (1996). [2] H. Reimerdes et al., Physical Review Letters, 98,055001 (2007). [3] M. Takechi et al., Physical Review Letters, 98,055002 (2007). [4] B. Hu and R. Betti, Physical Review Letters, 93,105002 (2004).

  14. Impregnated netting slows infestation by Triatoma infestans.

    Science.gov (United States)

    Levy, Michael Z; Quíspe-Machaca, Victor R; Ylla-Velasquez, Jose L; Waller, Lance A; Richards, Jean M; Rath, Bruno; Borrini-Mayori, Katty; del Carpio, Juan G Cornejo; Cordova-Benzaquen, Eleazar; McKenzie, F Ellis; Wirtz, Robert A; Maguire, James H; Gilman, Robert H; Bern, Caryn

    2008-10-01

    We used sentinel animal enclosures to measure the rate of infestation by the Chagas disease vector, Triatoma infestans, in an urban community of Arequipa, Peru, and to evaluate the effect of deltamethrin-impregnated netting on that rate. Impregnated netting decreased the rate of infestation of sentinel enclosures (rate ratio, 0.23; 95% confidence interval, 0.13-0.38; P < 0.001), controlling for the density of surrounding vector populations and the distance of these to the sentinel enclosures. Most migrant insects were early-stage nymphs, which are less likely to carry the parasitic agent of Chagas disease, Trypanosoma cruzi. Spread of the vector in the city therefore likely precedes spread of the parasite. Netting was particularly effective against adult insects and late-stage nymphs; taking into account population structure, netting decreased the reproductive value of migrant populations from 443.6 to 40.5. Impregnated netting can slow the spread of T. infestans and is a potentially valuable tool in the control of Chagas disease.

  15. 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.

  16. 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.

  17. 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...

  18. 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).

  19. Membrane binding domains

    OpenAIRE

    Hurley, James H.

    2006-01-01

    Eukaryotic signaling and trafficking proteins are rich in modular domains that bind cell membranes. These binding events are tightly regulated in space and time. The structural, biochemical, and biophysical mechanisms for targeting have been worked out for many families of membrane binding domains. This review takes a comparative view of seven major classes of membrane binding domains, the C1, C2, PH, FYVE, PX, ENTH, and BAR domains. These domains use a combination of specific headgroup inter...

  20. 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.

  1. 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.

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

    OpenAIRE

    Sojin Jung; Byoungho Jin

    2016-01-01

    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 slo...

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

    OpenAIRE

    Michele eBellesi; Brady A Riedner; Garcia-Molina, Gary N.; Chiara eCirelli; Giulio eTononi

    2014-01-01

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

  4. 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.

  5. Comparative Response of Platelet fV and Plasma fV to Activated Protein C and Relevance to a Model of Acute Traumatic Coagulopathy

    Science.gov (United States)

    2014-06-12

    Bovill EG, Wickerham DL, Buckley L, et al. (2003) Effect of tamoxifen on venous thrombosis risk factors in women without cancer: the Breast Cancer...1999) Extensive venous and arterial thrombosis associated with an inhibitor to activated protein C. Blood 94: 895 901. 31. Cushman M, Costantino JP...reduces fIIa production which reduces TAFI activation [19]. In trauma, activated platelets release Platelet Factor 4 (PF4), which acts as a soluble cofactor

  6. New functional assays to selectively quantify the activated protein C- and tissue factor pathway inhibitor-cofactor activities of protein S in plasma.

    Science.gov (United States)

    Alshaikh, N A; Rosing, J; Thomassen, M C L G D; Castoldi, E; Simioni, P; Hackeng, T M

    2017-02-17

    Essentials Protein S is a cofactor of activated protein C (APC) and tissue factor pathway inhibitor (TFPI). There are no assays to quantify separate APC and TFPI cofactor activities of protein S in plasma. We developed assays to measure the APC- and TFPI-cofactor activities of protein S in plasma. The assays were sensitive to protein S deficiency, and not affected by the Factor V Leiden mutation.

  7. Protein C, protein S, antithrombin III, and hyperfibrinogenemia in deep vein thrombosis (DVT among patients who underwent high risk orthopaedic surgery

    Directory of Open Access Journals (Sweden)

    Ismail Ismail

    2004-03-01

    Full Text Available Post operative DVT  is believed to be rare in Indonesia, and so is trombophilia. It is necessary to know  the incidence of postoperative DVT in Indonesia and thrombophlia profile (protein C, S, AT III deficiency and hyperfibrinogenemia in DVT and non DVT patient who underwent orthopedic surgery involving the hip and knee (high risk surgery. A cross sectional study was conducted in 20 patients who underwent surgery  involving the hip (total hip replacement  and fixation of proximal femoral fracture and knee (total knee replacement and fixation of  distal femoral fracture. Protein C, protein S, antithrombin III, and fibrinogen were examined in day 5 post operative, as well as with compression/Doppler USG between day 10 to 21 post operative, and confirmed by venography  if USG findings was positive. Post operative DVT were found in 5 of  20  patients (25%. Deficiency of protein C (P= 0.46 protein S (P= 0.81, antithrombin III (P= 0.46, and hyperfibrinogenemia (P= 0.0547 did not correlate to post operative DVT. However, hyperfibrinogenemia was found to be a risk factor to post operative DVT (attributable risk= 1. Other confounding factor such as diabetes mellitus (P= 1.0, obesity (P= 0.28, hypertention (P= 1.0, hypertrigliseridemia, and hypercholesterolemia did not correlate to post operative DVT. The study suggested  the existence of postoperative DVT cases  in Indonesia. Hyperfibrinogenemia is a risk factor to promote post operative DVT. Deep vein thrombosis  did not correlate to protein S, protein C, and antithrombin III deficiency. (Med J Indones 2004; 13: 24-30Keywords: Thrombophilia, hip, knee, venography

  8. 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...

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  10. TRANSLATION START SITE MULTIPLICITY OF THE CCAAT ENHANCER-BINDING PROTEIN-ALPHA MESSENGER-RNA IS DICTATED BY A SMALL 5' OPEN READING FRAME

    NARCIS (Netherlands)

    CALKHOVEN, CF; BOUWMAN, PRJ; SNIPPE, L; AB, G

    1994-01-01

    The CCAAT/enhancer binding proteins (C/EBP) alpha and beta of the bZIP family of transcription factors each occur as multiple forms due to translation initiation at different in-frame AUG codons from the same messenger RNA. The C/EBP alpha mRNAs of chicken, rat and Xenopus all contain a small 5' ope

  11. 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.

  12. 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.

  13. 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.

  14. 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).

  15. Complement protein C1q-mediated neuroprotection is correlated with regulation of neuronal gene and microRNA expression.

    Science.gov (United States)

    Benoit, Marie E; Tenner, Andrea J

    2011-03-02

    Activation of the complement cascade, a powerful effector mechanism of the innate immune system, is associated with neuroinflammation but also with elimination of inappropriate synapses during development. Synthesis of C1q, a recognition component of the complement system, occurs in brain during ischemia/reperfusion and Alzheimer's disease, suggesting that C1q may be a response to injury. In vitro, C1q, in the absence of other complement proteins, improves neuronal viability and neurite outgrowth and prevents β-amyloid-induced neuronal death, suggesting that C1q may have a direct neuroprotective role. Here, investigating the molecular basis for this neuroprotection in vitro, addition of C1q to rat primary cortical neurons significantly upregulated expression of genes associated with cholesterol metabolism, such as cholesterol-25-hydroxylase and insulin induced gene 2, and transiently decreased cholesterol levels in neurons, known to facilitate neurite outgrowth. In addition, the expression of syntaxin-3 and its functional association with synaptosomal-associated protein 25 was increased. C1q also increased the nuclear translocation of cAMP response element-binding protein and CCAAT/enhancer-binding protein-δ (C/EBP-δ), two transcription factors involved in nerve growth factor (NGF) expression and downregulated specific microRNAs, including let-7c that is predicted to target (and thus inhibit) NGF and neurotrophin-3 (NT-3) mRNA. Accordingly, C1q increased expression of NGF and NT-3, and small interfering RNA inhibition of C/EBP-δ, NGF, or NT-3 expression prevented the C1q-dependent neurite outgrowth. No such neuroprotective effect is seen in the presence of C3a or C5a. Finally, the induced neuronal gene expression required conformationally intact C1q. These results show that C1q can directly promote neuronal survival, thereby demonstrating new interactions between immune proteins and neuronal cells that may facilitate neuroprotection.

  16. Ureaplasma urealyticum binds mannose-binding lectin.

    Science.gov (United States)

    Benstein, Barbara D; Ourth, Donald D; Crouse, Dennis T; Shanklin, D Radford

    2004-10-01

    Mannose-binding C-type lectin (MBL) is an important component of innate immunity in mammals. Mannose-binding lectin (MBL), an acute phase protein, acts as an opsonin for phagocytosis and also activates the mannan-binding lectin complement pathway. It may play a particularly significant role during infancy before adequate specific protection can be provided by the adaptive immune system. Ureaplasma urealyticum has been linked to several diseases including pneumonia and chronic lung disease (CLD) in premature infants. We therefore investigated the ability of U. urealyticum to bind MBL. A guinea pig IgG anti-rabbit-MBL antiserum was produced. An immunoblot (dot-blot) assay done on nitrocellulose membrane determined that the anti-MBL antibody had specificity against both rabbit and human MBL. Pure cultures of U. urealyticum, serotype 3, were used to make slide preparations. The slides containing the organisms were then incubated with nonimmune rabbit serum containing MBL. Ureaplasma was shown to bind rabbit MBL with an immunocytochemical assay using the guinea pig IgG anti-rabbit MBL antiserum. Horseradish peroxidase (HRP)-labeled anti-guinea pig IgG was used to localize the reaction. The anti-MBL antiserum was also used in an immunocytochemical assay to localize U. urealyticum in histological sections of lungs from mice specifically infected with this organism. The same method also indicated binding of MBL by ureaplasma in human lung tissue obtained at autopsy from culture positive infants. Our results demonstrate that ureaplasma has the capacity to bind MBL. The absence of MBL may play a role in the predisposition of diseases related to this organism.

  17. Ligand binding mechanics of maltose binding protein.

    Science.gov (United States)

    Bertz, Morten; Rief, Matthias

    2009-11-13

    In the past decade, single-molecule force spectroscopy has provided new insights into the key interactions stabilizing folded proteins. A few recent studies probing the effects of ligand binding on mechanical protein stability have come to quite different conclusions. While some proteins seem to be stabilized considerably by a bound ligand, others appear to be unaffected. Since force acts as a vector in space, it is conceivable that mechanical stabilization by ligand binding is dependent on the direction of force application. In this study, we vary the direction of the force to investigate the effect of ligand binding on the stability of maltose binding protein (MBP). MBP consists of two lobes connected by a hinge region that move from an open to a closed conformation when the ligand maltose binds. Previous mechanical experiments, where load was applied to the N and C termini, have demonstrated that MBP is built up of four building blocks (unfoldons) that sequentially detach from the folded structure. In this study, we design the pulling direction so that force application moves the two MBP lobes apart along the hinge axis. Mechanical unfolding in this geometry proceeds via an intermediate state whose boundaries coincide with previously reported MBP unfoldons. We find that in contrast to N-C-terminal pulling experiments, the mechanical stability of MBP is increased by ligand binding when load is applied to the two lobes and force breaks the protein-ligand interactions directly. Contour length measurements indicate that MBP is forced into an open conformation before unfolding even if ligand is bound. Using mutagenesis experiments, we demonstrate that the mechanical stabilization effect is due to only a few key interactions of the protein with its ligand. This work illustrates how varying the direction of the applied force allows revealing important details about the ligand binding mechanics of a large protein.

  18. 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......(g) for the combined system is significantly enhanced relative to slow light based on purely material or waveguide dispersion....

  19. The impact of cortical deafferentation on the neocortical slow oscillation.

    Science.gov (United States)

    Lemieux, Maxime; Chen, Jen-Yung; Lonjers, Peter; Bazhenov, Maxim; Timofeev, Igor

    2014-04-16

    Slow oscillation is the main brain rhythm observed during deep sleep in mammals. Although several studies have demonstrated its neocortical origin, the extent of the thalamic contribution is still a matter of discussion. Using electrophysiological recordings in vivo on cats and computational modeling, we found that the local thalamic inactivation or the complete isolation of the neocortical slabs maintained within the brain dramatically reduced the expression of slow and fast oscillations in affected cortical areas. The slow oscillation began to recover 12 h after thalamic inactivation. The slow oscillation, but not faster activities, nearly recovered after 30 h and persisted for weeks in the isolated slabs. We also observed an increase of the membrane potential fluctuations recorded in vivo several hours after thalamic inactivation. Mimicking this enhancement in a network computational model with an increased postsynaptic activity of long-range intracortical afferents or scaling K(+) leak current, but not several other Na(+) and K(+) intrinsic currents was sufficient for recovering the slow oscillation. We conclude that, in the intact brain, the thalamus contributes to the generation of cortical active states of the slow oscillation and mediates its large-scale synchronization. Our study also suggests that the deafferentation-induced alterations of the sleep slow oscillation can be counteracted by compensatory intracortical mechanisms and that the sleep slow oscillation is a fundamental and intrinsic state of the neocortex.

  20. Helping the Slow-Reader in the Primary School Classroom.

    Science.gov (United States)

    Burke, Edmund V.

    1988-01-01

    A strategy is proposed for primary teachers to use with children who have reading difficulties. It includes developing a profile of each slow reader, testing each slow reader to determine reading level and specific weaknesses, and using certain practical methods to help solve the problem. (two references) (LB)

  1. Slow Light at High Frequencies in an Amplifying Semiconductor Waveguide

    DEFF Research Database (Denmark)

    Öhman, Filip; Yvind, Kresten; Mørk, Jesper

    2006-01-01

    We demonstrate slow-down of a modulated light signal in a semiconductor waveguide. Concatenated amplifying and absorbing sections simultaneously achieve both amplification and a controllable time delay at 15 GHz.......We demonstrate slow-down of a modulated light signal in a semiconductor waveguide. Concatenated amplifying and absorbing sections simultaneously achieve both amplification and a controllable time delay at 15 GHz....

  2. 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

  3. Ultra Slow Muon Project at J-PARC MUSE

    Science.gov (United States)

    Miyake, Yasuhiro; Ikedo, Yutaka; Shimomura, Koichiro; Strasser, Patrick; Takashi, Nagatomo; Nakamura, Jumpei; Makimura, Shunsuke; Kawamura, Naritoshi; Fujimori, Hiroshi; Koda, Akihiro; Kobayashi, Yasuo; Nishiyama, Kusuo; Kadono, Ryosuke; Higemoto, Wataru; Ito, Takashi; Ogitsu, Toru; Makida, Yasuhiro; Sasaki, Kenichi; Adachi, Taihei; Torikai, Eiko

    We have been proceeding the Ultra Slow Muon project at J-PARC MUSE(MUon Science Establishment). As a first mission, we constructed the U-Line and succeeded in extracting the world highest intensity pulsed surface muons, 2,500,000 muons per pulse (6.4 × 107/s at 212 kW proton beam intensity, corresponding to 3 × 108/s at 1 MW) to the U1 experimental area. As the second mission, we have installed a Mu chamber to stop such intense pulsed surface muons towards a hot tungsten target for generating an intense ultra slow muon beam, as well as a slow ion optics to accelerate and transport ultra slow muons to the U1A and U1B areas where μ+ SR spectrometers are located. We are standing on the stage we are ready to generate ultra slow muons, if J-PARC operation is approved.

  4. 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...

  5. 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.

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

    CERN Document Server

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

    2014-01-01

    Slow light is a fascinating physical effect, raising fundamental questions related to our understanding of light-matter interactions as well as offering new possibilities for photonic devices. From the first demonstrations of slow light propagation in ultra-cold atomic gasses, solid-state Ruby and photonic crystal structures, focus has shifted to applications, with slow light offering the ability to enhance and control light-matter interactions. The demonstration of tuneable delay lines, enhanced nonlinearities and spontaneous emission, enlarged spectral sensitivity and increased phase shifts illustrate the possibilities enabled by slow light propagation, with microwave photonics emerging as one of the promising applications. Here, we demonstrate that slow light can be used to control and increase the gain coefficient of an active semiconductor waveguide. The effect was theoretically predicted but not yet experimentally demonstrated. These results show a route towards realizing ultra-compact optical amplifier...

  7. Protein Binding Pocket Dynamics.

    Science.gov (United States)

    Stank, Antonia; Kokh, Daria B; Fuller, Jonathan C; Wade, Rebecca C

    2016-05-17

    The dynamics of protein binding pockets are crucial for their interaction specificity. Structural flexibility allows proteins to adapt to their individual molecular binding partners and facilitates the binding process. This implies the necessity to consider protein internal motion in determining and predicting binding properties and in designing new binders. Although accounting for protein dynamics presents a challenge for computational approaches, it expands the structural and physicochemical space for compound design and thus offers the prospect of improved binding specificity and selectivity. A cavity on the surface or in the interior of a protein that possesses suitable properties for binding a ligand is usually referred to as a binding pocket. The set of amino acid residues around a binding pocket determines its physicochemical characteristics and, together with its shape and location in a protein, defines its functionality. Residues outside the binding site can also have a long-range effect on the properties of the binding pocket. Cavities with similar functionalities are often conserved across protein families. For example, enzyme active sites are usually concave surfaces that present amino acid residues in a suitable configuration for binding low molecular weight compounds. Macromolecular binding pockets, on the other hand, are located on the protein surface and are often shallower. The mobility of proteins allows the opening, closing, and adaptation of binding pockets to regulate binding processes and specific protein functionalities. For example, channels and tunnels can exist permanently or transiently to transport compounds to and from a binding site. The influence of protein flexibility on binding pockets can vary from small changes to an already existent pocket to the formation of a completely new pocket. Here, we review recent developments in computational methods to detect and define binding pockets and to study pocket dynamics. We introduce five

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

    Directory of Open Access Journals (Sweden)

    Michele eBellesi

    2014-10-01

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

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

    Science.gov (United States)

    Bellesi, Michele; Riedner, Brady A; Garcia-Molina, Gary N; Cirelli, Chiara; Tononi, Giulio

    2014-01-01

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

  10. 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 ...

  11. 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.

  12. 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

  13. Origin of Pseudotachylites during slow creep experiments

    Science.gov (United States)

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

    2012-04-01

    structures, bubbles, and bubble trains following the local flow pattern, corroded clasts and amorphous glass identified by TEM. The chemical composition of the pseudotachylites varies depending on the precursor material and is in general more ferromagnesian and basic compared to the bulk rock indicating preferred melting of biotite. The calculated temperature increase due to shear heating is at the most 5°C. High stresses cause pervasive comminution: the smallest crystalline fragments within the bubbly melt have a grain diameter of 10 nm. Nanomaterials exhibit a 'melting point depression' (dependence of melting point on grain size) which allows melting well below bulk melting temperatures. Thus, it seems that melting is a continuation of the comminution once the rock has reached small enough grain size. We therefore suggest that pseudotachylites may also form as 'mechanical melts' at slow displacement rates without the necessity of reaching high temperatures.

  14. Interaction of C4-binding protein with cell-bound C4b. A quantitative analysis of binding and the role of C4-binding protein in proteolysis of cell-bound C4b

    OpenAIRE

    1983-01-01

    Purified C4-binding protein (C4-bp) was shown to bind to cell-bound C4b by radioactive tracer techniques. With EAC4 bearing greater than 3,000 C4b-molecules/cell, the number of C4-bp molecules bound was directly proportional to the number of C4b molecule on the cell surface; EAC4 bearing less than 3,000 C4b-molecules/cell bound a very small amount of C4-bp. Scatchard analysis of binding of C4-bp indicated an equilibrium constant of 4.6 X 10(8) L/M and a maximum of 0.43 C4-bp molecules bound p...

  15. Regeneration of frog twitch and slow muscle fibers after mincing.

    Science.gov (United States)

    Schmidt, H; Emser, W

    1985-10-01

    Iliofibularis muscles of Rana temporaria were minced and allowed to regenerate in the iliofibularis or the sartorius bed of the same frog. Regenerated muscles were examined for the presence of slow muscle fibers using electrophysiologic, histochemical, and contractile parameters. Muscle regeneration from sartorius mince was also studied. Regeneration was more successful from iliofibularis than from sartorius mince, and the iliofibularis bed was more favorable for regeneration than the sartorius bed for both types of muscle. Twitch fibers regenerated within a few months, but slow fibers could not be identified earlier than 14 months after muscle destruction. Slow muscle fibers regenerated only from iliofibularis mince, both orthotopically and heterotopically. All regenerates capable of maintaining a K-contracture contained histochemically identified slow fibers; the membrane properties of electrophysiologically identified slow fibers were normal. It is concluded that slow muscle fibers regenerate only from the remnants of a muscle that contains slow fibers. The results are discussed with respect to the role of innervating nerve fibers.

  16. Influence of fast and slow alkali myosin light chain isoforms on the kinetics of stretch-induced force transients of fast-twitch type IIA fibres of rat.

    Science.gov (United States)

    Andruchov, Oleg; Galler, Stefan

    2008-03-01

    This study contributes to understand the physiological role of slow myosin light chain isoforms in fast-twitch type IIA fibres of skeletal muscle. These isoforms are often attached to the myosin necks of rat type IIA fibres, whereby the slow alkali myosin light chain isoform MLC1s is much more frequent and abundant than the slow regulatory myosin light chain isoform MLC2s. In the present study, single-skinned rat type IIA fibres were maximally Ca(2+) activated and subjected to stepwise stretches for causing a perturbation of myosin head pulling cycles. From the time course of the resulting force transients, myosin head kinetics was deduced. Fibres containing MLC1s exhibited slower kinetics independently of the presence or absence of MLC2s. At the maximal MLC1s concentration of about 75%, the slowing was about 40%. The slowing effect of MLC1s is possibly due to differences in the myosin heavy chain binding sites of the fast and slow alkali MLC isoforms, which changes the rigidity of the myosin neck. Compared with the impact of myosin heavy chain isoforms in various fast-twitch fibre types, the influence of MLC1s on myosin head kinetics of type IIA fibres is much smaller. In conclusion, the physiological role of fast and slow MLC isoforms in type IIA fibres is a fine-tuning of the myosin head kinetics.

  17. 国产蛇毒激活血浆蛋白C的研究%Identification of protein c activator from nine species of Chinese snake venoms

    Institute of Scientific and Technical Information of China (English)

    孙林光; 管锦霞; 黄劭; 余清声

    2001-01-01

    目的:从9种国产蛇毒中筛选具有激活血浆蛋白C作用的蛇毒。方法:运用活化部分凝血活酶时间(APTT)和发色底物实验分别观察抗凝活性和酰胺酶活性,综合抗凝活性和酰胺酶活性确定蛋白C蛇毒激活作用。结果:在9种国产蛇毒中烙铁头蛇毒及蝮蛇毒在1.5 mg/L浓度下即使人血浆纯蛋白C产生酰胺酶活性,并使APTT显著延长。结论:9种国产蛇毒中烙铁头蛇毒及蝮蛇毒具有激活人体血浆蛋白C成为活化蛋白C(APC)的作用。%AIM:To determine which species of snake venoms contained protein c activator among 9 species of Chinese snake venoms. METHODS: Anticoagulant activity was examined by activated partial thromboplastin time (APTT) assay,and amidolytic activity was measured with activated protein c (APC) specific chromogenic peptide substrate-chromozy APC. RESULTS: Among 9 species of Chinese snake venoms,Trimeresurus mucrosquamatus venom and Agkistrodon halys venom were not only able to generate amidolytic activity from purified human PC, but also prolonged APTT strongly even at such a concentration as 1.5 mg/L.CONCLUSION: Trimeresurus mucrosquamatus venom and Agkistrodon halys venom contain protein c activator which activating human plasma PC into APC.

  18. 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.

  19. 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

  20. 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.

  1. Complement-activated oligodendroglia: a new pathogenic entity identified by immunostaining with antibodies to human complement proteins C3d and C4d.

    Science.gov (United States)

    Yamada, T; Akiyama, H; McGeer, P L

    1990-05-04

    Clusters of oligodendroglial fibers were identified immunohistochemically in human brain tissue with antibodies to the complement proteins C3d and C4d in several neurological disorders. These included Pick's, Huntington's, Parkinson's and Alzheimer's disease, amyotrophic lateral sclerosis, progressive supranuclear palsy and Shy-Drager syndrome. These complement-activated oligodendroglia occurred in selected areas of gray and white matter. They were rarely observed in control tissue. Immunogold electron microscopy established that the C4d antibody was attached to degenerating myelin sheaths. These data indicate attachment of classical complement pathway proteins to selective oligodendroglia in several neurological disorders.

  2. Fast and catalyst-free hydrazone ligation via ortho-halo-substituted benzaldehydes for protein C-terminal labeling at neutral pH.

    Science.gov (United States)

    Xu, Yang; Xu, Ling; Xia, Yuan; Guan, Chao-Jian; Guo, Qing-Xiang; Fu, Yao; Wang, Chen; Li, Yi-Ming

    2015-08-28

    Rapid and catalyst-free hydrazone ligation reaction between ortho-halobenzaldehyde derivatives and peptide/protein hydrazides was observed at neutral pH and room temperature. 2-Chlorobenzaldehyde exhibited the fastest reaction and highest conversion rates among the series of ortho-halobenzaldehydes. The resulting hydrazone-containing bioconjugation products were also found to be fairly stable under experimental conditions. The new ligation strategy was successfully used for protein C-terminal labeling and should provide a practical approach for the modification of proteins.

  3. Slow Food: por um alimento bom, limpo e justo

    OpenAIRE

    Fabiele Porazzi

    2012-01-01

    REVIEW:PETRINI, Carlo. Slow Food: princípios da nova gastronomia. Trad. de Renata Lúcia Botina. São Paulo: Editora Senac, 2009. 245 p. RESEÑA:PETRINI, Carlo. Slow Food: princípios da nova gastronomia. Trad. de Renata Lúcia Botina. São Paulo: Editora Senac, 2009. 245 p. http://dx.doi.org/10.5007/1807-1384.2012v9n1p384 RESENHA:PETRINI, Carlo. Slow Food: princípios da nova gastronomia. Trad. de Renata Lúcia Botina. São Paulo: Editora Senac, 2009. 245 p.

  4. 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.

  5. 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

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

    CERN Document Server

    Perkowitz, Sidney

    2011-01-01

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

  7. On Slow Light as a Black Hole Analogue

    CERN Document Server

    Unruh, W G

    2003-01-01

    Although slow light (electromagnetically induced transparency) would seem an ideal medium in which to institute a ``dumb hole'' (black hole analog), it suffers from a number of problems. We show that the high phase velocity in the slow light regime ensures that the system cannot be used as an analog displaying Hawking radiation. Even though an appropriately designed slow-light set-up may simulate classical features of black holes -- such as horizon, mode mixing, Bogoliubov coefficients, etc. -- it does not reproduce the related quantum effects. PACS: 04.70.Dy, 04.80.-y, 42.50.Gy, 04.60.-m.

  8. Origin of the slow afterhyperpolarization and slow rhythmic bursting in striatal cholinergic interneurons.

    Science.gov (United States)

    Wilson, Charles J; Goldberg, Joshua A

    2006-01-01

    Striatal cholinergic interneurons recorded in slices exhibit three different firing patterns: rhythmic single spiking, irregular bursting, and rhythmic bursting. The rhythmic single-spiking pattern is governed mainly by a prominent brief afterhyperpolarization (mAHP) that follows single spikes. The mAHP arises from an apamin-sensitive calcium-dependent potassium current. A slower AHP (sAHP), also present in these neurons, becomes prominent during rhythmic bursting or driven firing. Although not apamin sensitive, the sAHP is caused by a calcium-dependent potassium conductance. It is not present after blockade of calcium current with cadmium or after calcium is removed from the media or when intracellular calcium is buffered with bis-(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid. It reverses at the potassium equilibrium potential. It can be generated by subthreshold depolarizations and persists after blockade of sodium currents by tetrodotoxin. It is slow, being maximal approximately 1 s after depolarization onset, and takes several seconds to decay. It requires >300-ms depolarizations to become maximally activated. Its voltage sensitivity is sigmoidal, with a half activation voltage of -40 mV. We conclude the sAHP is a high-affinity apamin-insensitive calcium-dependent potassium conductance, triggered by calcium currents partly activated at subthreshold levels. In combination with those calcium currents, it accounts for the slow oscillations seen in a subset of cholinergic interneurons exhibiting rhythmic bursting. In all cholinergic interneurons, it contributes to the slowdown or pause in firing that follows driven activity or prolonged subthreshold depolarizations and is therefore a candidate mechanism for the pause response observed in cholinergic neurons in vivo.

  9. On Binding Domains

    NARCIS (Netherlands)

    Everaert, M.B.H.

    2005-01-01

    In this paper I want to explore reasons for replacing Binding Theory based on the anaphor-pronoun dichotomy by a Binding Theory allowing more domains restricting/defining anaphoric dependencies. This will, thus, have consequences for the partitioning of anaphoric elements, presupposing more types of

  10. 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)

  11. 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.

  12. 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

  13. Regulation of p53-mediated changes in the uPA-fibrinolytic system and in lung injury by loss of surfactant protein-C expression in alveolar epithelial cells.

    Science.gov (United States)

    Puthusseri, Bijesh; Marudamuthu, Amarnath S; Tiwari, Nivedita; Fu, Jian; Idell, Steven; Shetty, Sreerama

    2017-04-06

    Pulmonary surfactant protein-C (SP-C) expression by type II alveolar epithelial cells (AECs) is markedly reduced in diverse types of lung injuries and is often associated with AEC apoptosis. It is unclear whether loss of SP-C contributes to the increased p53 and urokinase-type plasminogen activator (uPA) system cross talk and apoptosis of AECs. We therefore inhibited SP-C expression in human and murine AECs using lentivirus vector expressing shRNA and tested p53 and downstream changes in uPA-fibrinolytic system. Inhibition of SP-C expression in AECs induced p53 and activated caspase-3, indicating AEC apoptosis. We also found that bleomycin or cigarette smoke exposure failed to inhibit SP-C expression or apoptosis in AECs in p53- and plasminogen activator inhibitor-1 (PAI-1)-deficient mice. Depletion of SP-C expression by lentiviral SP-C shRNA in PAI-1-deficient mice failed to induce p53 or apoptosis in AECs, while it increased both AEC p53 and apoptosis in wild type or uPA-deficient mice. SP-C inhibition in AECs also increased in CXCL1 and CXCL2, and their receptor CXCR2 as well as ICAM-1 expression, indicative of a pro-inflammatory response. Overexpression of p53-binding 3'UTR sequences in AECs inhibited PAI-1 induction while maintaining uPA and uPAR protein and mRNA expression. Further, caveolin-1 expression and phosphorylation were increased in AECs indicating an intricate link between caveolin-1 and Src kinase-mediated cell signalling and AEC apoptosis due to loss of SP-C expression through p53 and uPA system-mediated cross-talk. The role of uPA, PAI-1 and p53 in the regulation of AEC apoptosis after injury was also determined in knock out mice.

  14. Thermodynamics of fragment binding.

    Science.gov (United States)

    Ferenczy, György G; Keserű, György M

    2012-04-23

    The ligand binding pockets of proteins have preponderance of hydrophobic amino acids and are typically within the apolar interior of the protein; nevertheless, they are able to bind low complexity, polar, water-soluble fragments. In order to understand this phenomenon, we analyzed high resolution X-ray data of protein-ligand complexes from the Protein Data Bank and found that fragments bind to proteins with two near optimal geometry H-bonds on average. The linear extent of the fragment binding site was found not to be larger than 10 Å, and the H-bonding region was found to be restricted to about 5 Å on average. The number of conserved H-bonds in proteins cocrystallized with multiple different fragments is also near to 2. These fragment binding sites that are able to form limited number of strong H-bonds in a hydrophobic environment are identified as hot spots. An estimate of the free-energy gain of H-bond formation versus apolar desolvation supports that fragment sized compounds need H-bonds to achieve detectable binding. This suggests that fragment binding is mostly enthalpic that is in line with their observed binding thermodynamics documented in Isothermal Titration Calorimetry (ITC) data sets and gives a thermodynamic rationale for fragment based approaches. The binding of larger compounds tends to more rely on apolar desolvation with a corresponding increase of the entropy content of their binding free-energy. These findings explain the reported size-dependence of maximal available affinity and ligand efficiency both behaving differently in the small molecule region featured by strong H-bond formation and in the larger molecule region featured by apolar desolvation.

  15. Effects of cervical self-stretching on slow vital capacity.

    Science.gov (United States)

    Han, Dongwook; Yoon, Nayoon; Jeong, Yeongran; Ha, Misook; Nam, Kunwoo

    2015-07-01

    [Purpose] This study investigated the effects of self-stretching of cervical muscles, because the accessory inspiratory muscle is considered to improve pulmonary function. [Subjects] The subjects were 30 healthy university students 19-21 years old who did not have any lung disease, respiratory dysfunction, cervical injury, or any problems upon cervical stretching. [Methods] Spirometry was used as a pulmonary function test to measure the slow vital capacity before and after stretching. The slow vital capacity of the experimental group was measured before and after cervical self-stretching. Meanwhile, the slow vital capacity of the control group, which did not perform stretching, was also measured before and after the intervention. [Results] The expiratory vital capacity, inspiratory reserve volume, and expiratory reserve volume of the experimental group increased significantly after the cervical self-stretching. [Conclusion] Self-stretching of the cervical muscle (i.e., the inspiratory accessory muscle) improves slow vital capacity.

  16. 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.

  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. Slow light enhancement and limitations in periodic media

    DEFF Research Database (Denmark)

    Grgic, Jure

    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......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...... and significant structures with numerical and analytical methods. By analyzing different structures, we show very general properties for limitation and enhancement in the slow light regime. Inherent imperfections of fabricated structures such as a material loss and structural disorder have a strong influence...

  19. 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....

  20. On the stability of slow neutron combustion in astrophysical objects

    Energy Technology Data Exchange (ETDEWEB)

    Horvath, J.E.; Benvenuto, O.G.

    1988-11-03

    The problem of slow neutron combustion in astrophysical objects is studied from the hydrodynamical point of view, showing that unless the existence of unknown stabilizing effects, the process seems to be absolutely unstable. It is shown that the slow combustion is likely to become a fast combustion mode called detonation. Some possible consequences of this instability for neutron stars and type II supernovae are presented and discussed.

  1. 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 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....

  2. 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...

  3. 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....

  4. Slow Tech: The Bridge between Computer Ethics and Business Ethics

    OpenAIRE

    Patrignani, Norberto; Whitehouse, Diane

    2014-01-01

    Part 1: Society, Social Responsibility, Ethics and ICT; International audience; This paper addresses the difficult task of implementing the concept of Slow Tech, that is, information and communication technology (ICT) that is good, clean and fair, in a business environment. It investigates the democratic, environmental, and social challenges currently facing ICT vendors. More specifically, it examines the opportunities available for these companies to use Slow Tech as a bridging mechanism bet...

  5. Slow Fashion : Tailoring a Strategic Approach towards Sustainability

    OpenAIRE

    Cataldi, Carlotta; Dickson, Maureen; Grover, Crystal

    2010-01-01

    This research explores one avenue for achieving sustainability within the fashion industry; which as it exists today is unsustainable. The Slow Fashion movement has an existing foundation in the larger fashion industry and is already making strides towards sustainability. The authors used this opportunity to examine a strategic approach, as its current approach is ad hoc. First, the authors assessed the Slow Fashion movement using the 5 level Framework for Strategic Sustainable Development. T...

  6. 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....

  7. Cardiac actions of phencyclidine in isolated guinea pig and rat heart: possible involvement of slow channels

    Energy Technology Data Exchange (ETDEWEB)

    Temma, K.; Akera, T.; Ng, Y.C.

    1985-03-01

    The mechanisms responsible for the positive inotropic effect of phencyclidine were studied in isolated preparations of guinea pig and rat heart. In electrically paced left atrial muscle preparations, phencyclidine increased the force of contraction; rat heart muscle preparations were more sensitive than guinea pig heart muscle preparations. The positive inotropic effect of phencyclidine was not significantly reduced by a combination of phentolamine and nadolol; however, the effect was competitively blocked by verapamil in the presence of phentolamine and nadolol. Inhibition of the outward K+ current by tetraethylammonium chloride also produced a positive inotropic effect; however, the effect of tetraethylammonium was reduced by phentolamine and nadolol, and was almost insensitive to verapamil. The inotropic effect of phencyclidine was associated with a marked prolongation of the action potential duration and a decrease in maximal upstroke velocity of the action potential, with no change in the resting membrane potential. The specific (/sup 3/H)phencyclidine binding observed with membrane preparations from guinea pig ventricular muscle was saturable with a single class of high-affinity binding site. This binding was inhibited by verapamil, diltiazem, or nitrendipine, but not by ryanodine or tetrodotoxin. These results suggest that the positive inotropic effect of phencyclidine results from enhanced Ca/sup 2 +/ influx via slow channels, either by stimulation of the channels or secondary to inhibition of outward K/sup +/ currents.

  8. 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.

  9. Implications of the Deep Minimum for Slow Solar Wind Origin

    Science.gov (United States)

    Antiochos, S. K.; Mikic, Z.; Lionello, R.; Titov, V. S.; Linker, J. A.

    2009-12-01

    The origin of the slow solar wind has long been one of the most important problems in solar/heliospheric physics. Two observational constraints make this problem especially challenging. First, the slow wind has the composition of the closed-field corona, unlike the fast wind that originates on open field lines. Second, the slow wind has substantial angular extent, of order 30 degrees, which is much larger than the widths observed for streamer stalks or the widths expected theoretically for a dynamic heliospheric current sheet. We propose that the slow wind originates from an intricate network of narrow (possibly singular) open-field corridors that emanate from the polar coronal hole regions. Using topological arguments, we show that these corridors must be ubiquitous in the solar corona. The total solar eclipse in August 2008, near the lowest point of the Deep Minimum, affords an ideal opportunity to test this theory by using the ultra-high resolution Predictive Science's (PSI) eclipse model for the corona and wind. Analysis of the PSI eclipse model demonstrates that the extent and scales of the open-field corridors can account for both the angular width of the slow wind and its closed-field composition. We discuss the implications of our slow wind theory for the structure of the corona and heliosphere at the Deep Minimum and describe further observational and theoretical tests. This work has been supported by the NASA HTP, SR&T, and LWS programs.

  10. Plasma depletion layer: the role of the slow mode waves

    Directory of Open Access Journals (Sweden)

    Y. L. Wang

    2004-12-01

    Full Text Available The plasma depletion layer (PDL is a layer on the sunward side of the magnetopause with lower plasma density and higher magnetic field compared to their corresponding values in the upstream magnetosheath. The depletion layer usually occurs during northward (IMF conditions with low magnetic shear across the magnetopause. We have previously validated the Raeder global model by comparing the computed formation of a magnetosheath density depletion with in-situ observations. We also have performed a detailed force analysis and found the varying roles that different MHD forces play along the path of a plasma parcel flowing around the magnetopause. That study resulted in a new description of the behavior of magnetosheath magnetic flux tubes which better explains the plasma depletion along a flux tube. The slow mode waves have been observed in the magnetosheath and have been used to explain the formation of the PDL in some of the important PDL models. In this study, we extend our former work by investigating the possible role of the slow mode waves for the formation of the PDL, using global MHD model simulations. We propose a new technique to test where a possible slow mode front may occur in the magnetosheath by comparing the slow mode group velocity with the local flow velocity. We find that the slow mode fronts can exist in certain regions in the magnetosheath under certain solar wind conditions. The existence and location of such fronts clearly depend on the IMF. We do not see from our global simulation results either the sharpening of the slow mode front into a slow mode shock or noticeable changes of the flow and field in the magnetosheath across the slow mode front, which implies that the slow mode front is not likely responsible for the formation of the PDL, at least for the stable solar wind conditions used in these simulations. Also, we do not see the two-layered slow mode structures shown in some observations and proposed in certain PDL

  11. CCAAT/enhancer binding protein Beta-2 is involved in growth hormone-regulated insulin-like growth factor-II gene expression in the liver of rainbow trout (Oncorhynchus mykiss)

    Science.gov (United States)

    Previously, we showed that levels of different CCAAT/enhancer binding protein (C/EBP) mRNAs in the liver of rainbow trout were modulated by GH and suggested that C/EBPs might be involved in GH induced IGF-II gene expression. As a step toward further investigation, we have developed monospecific poly...

  12. 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

  13. Cation binding site of cytochrome c oxidase: progress report.

    Science.gov (United States)

    Vygodina, Tatiana V; Kirichenko, Anna; Konstantinov, Alexander A

    2014-07-01

    Cytochrome c oxidase from bovine heart binds Ca(2+) reversibly at a specific Cation Binding Site located near the outer face of the mitochondrial membrane. Ca(2+) shifts the absorption spectrum of heme a, which allowed earlier the determination of the kinetic and equilibrium characteristics of the binding, and, as shown recently, the binding of calcium to the site inhibits cytochrome oxidase activity at low turnover rates of the enzyme [Vygodina, Т., Kirichenko, A., Konstantinov, A.A (2013). Direct Regulation of Cytochrome c Oxidase by Calcium Ions. PloS ONE 8, e74436]. This paper summarizes further progress in the studies of the Cation Binding Site in this group presenting the results to be reported at 18th EBEC Meeting in Lisbon, 2014. The paper revises specificity of the bovine oxidase Cation Binding Site for different cations, describes dependence of the Ca(2+)-induced inhibition on turnover rate of the enzyme and reports very high affinity binding of calcium with the "slow" form of cytochrome oxidase. This article is part of a Special Issue entitled: 18th European Bioenergetic Conference. Guest Editors: Manuela Pereira and Miguel Teixeira.

  14. 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 ...

  15. A comparative double-blind randomized trial of activated protein C and unfractionated heparin in the treatment of disseminated intravascular coagulation.

    Science.gov (United States)

    Aoki, Nobuo; Matsuda, Tamotsu; Saito, Hidehiko; Takatsuki, Kiyoshi; Okajima, Kenji; Takahashi, Hoyu; Takamatsu, Junki; Asakura, Hidesaku; Ogawa, Nobuya

    2002-06-01

    A randomized prospective double-blind trial was performed to compare the safety and efficacy of human activated protein C (APC) and unfractionated heparin for the treatment of disseminated intravascular coagulation (DIC). One hundred thirty-two patients with DIC were enrolled in this study: 63 patients received APC (12.5 U [2.5 microg]/kg body wt per hour) and 69 patients received heparin (8 U/kg body wt per hour) by intravenous infusion for 6 days. Forty-nine APC-treated patients and 55 heparin-treated patients were evaluated for efficacy, and 52 APC-treated patients and 55 heparin-treated patients were evaluated for safety. The 2 groups were similar with respect to sex, age, body weight, underlying diseases, and coagulation/fibrinolysis parameters before treatment. Aggravation of bleeding was seen after treatment in 8 patients receiving heparin, but in none of the patients receiving APC. The number of patients who showed alleviation of bleeding was significantly higher in the APC group than the heparin group (P = .009). The effects on DIC-related organ dysfunction were not significantly different between the 2 groups. Fibrinogen-fibrin degradation products, D-dimer, thrombin-antithrombin complex (TAT), and plasmin-plasmin inhibitor complex (PIC) were all significantly decreased by treatment in both groups. Fibrinogen, protein C, and antithrombin were significantly increased in the APC group, whereas only protein C was significantly increased in the heparin group. Platelet count in the nonleukemic group was significantly increased in those patients receiving APC but not increased in those patients receiving heparin. Improvement of coagulation/fibrinolysis was assessed by scoring 4 parameters (soluble fibrin monomers, D-dimer, TAT, and PIC), and the results indicated that the APC group showed significantly greater improvement than the heparin group (P = .046). There was, however, no significant difference in the rate of complete recovery from DIC between the 2

  16. Yersinia enterocolitica serum resistance proteins YadA and ail bind the complement regulator C4b-binding protein.

    Directory of Open Access Journals (Sweden)

    Vesa Kirjavainen

    Full Text Available Many pathogens are equipped with factors providing resistance against the bactericidal action of complement. Yersinia enterocolitica, a Gram-negative enteric pathogen with invasive properties, efficiently resists the deleterious action of human complement. The major Y. enterocolitica serum resistance determinants include outer membrane proteins YadA and Ail. Lipopolysaccharide (LPS O-antigen (O-ag and outer core (OC do not contribute directly to complement resistance. The aim of this study was to analyze a possible mechanism whereby Y. enterocolitica could inhibit the antibody-mediated classical pathway of complement activation. We show that Y. enterocolitica serotypes O:3, O:8, and O:9 bind C4b-binding protein (C4bp, an inhibitor of both the classical and lectin pathways of complement. To identify the C4bp receptors on Y. enterocolitica serotype O:3 surface, a set of mutants expressing YadA, Ail, O-ag, and OC in different combinations was tested for the ability to bind C4bp. The studies showed that both YadA and Ail acted as C4bp receptors. Ail-mediated C4bp binding, however, was blocked by the O-ag and OC, and could be observed only with mutants lacking these LPS structures. C4bp bound to Y. enterocolitica was functionally active and participated in the factor I-mediated degradation of C4b. These findings show that Y. enterocolitica uses two proteins, YadA and Ail, to bind C4bp. Binding of C4bp could help Y. enterocolitica to evade complement-mediated clearance in the human host.

  17. Inhibition of the ribonuclease H activity of HIV-1 reverse transcriptase by GSK5750 correlates with slow enzyme-inhibitor dissociation.

    Science.gov (United States)

    Beilhartz, Greg L; Ngure, Marianne; Johns, Brian A; DeAnda, Felix; Gerondelis, Peter; Götte, Matthias

    2014-06-06

    Compounds that efficiently inhibit the ribonuclease (RNase) H activity of the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) have yet to be developed. Here, we demonstrate that GSK5750, a 1-hydroxy-pyridopyrimidinone analog, binds to the enzyme with an equilibrium dissociation constant (K(d)) of ~400 nM. Inhibition of HIV-1 RNase H is specific, as DNA synthesis is not affected. Moreover, GSK5750 does not inhibit the activity of Escherichia coli RNase H. Order-of-addition experiments show that GSK5750 binds to the free enzyme in an Mg(2+)-dependent fashion. However, as reported for other active site inhibitors, binding of GSK5750 to a preformed enzyme-substrate complex is severely compromised. The bound nucleic acid prevents access to the RNase H active site, which represents a possible biochemical hurdle in the development of potent RNase H inhibitors. Previous studies suggested that formation of a complex with the prototypic RNase H inhibitor β-thujaplicinol is slow, and, once formed, it dissociates rapidly. This unfavorable kinetic behavior can limit the potency of RNase H active site inhibitors. Although the association kinetics of GSK5750 remains slow, our data show that this compound forms a long lasting complex with HIV-1 RT. We conclude that slow dissociation of the inhibitor and HIV-1 RT improves RNase H active site inhibitors and may circumvent the obstacle posed by the inability of these compounds to bind to a preformed enzyme-substrate complex.

  18. 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...

  19. Perceptions of the Slow Food Cultural Trend among the Youth

    Directory of Open Access Journals (Sweden)

    Lelia Voinea

    2016-11-01

    Full Text Available As they become increasingly aware of the importance of healthy eating and of the serious food imbalance caused by the overconsumption of industrial, ultra-processed and superorganoleptic food, consumers are now beginning to turn their attention to food choices guaranteeing both individual health and also of the environment . Thus, in recent years we are witnessing the rise of a cultural trend ‒ Slow Food. Slow Food has become an international movement that advocates for satisfying culinary pleasure, protects biological and cultural diversity, spread taste education, links "green" producers to consumers and believes that gastronomy intersects with politics, agriculture and ecology. Slow Food proposes a holistic approach to food problem, where the economic, sociocultural and environmental aspects are interlinked, being pursued as part of an overall strategy. In order to highlight the manner in which the principles of this cultural trend are perceived by the representatives of the new generation of consumers in Romania, exploratory research marketing was conducted among the students in the second year of the master’s program Quality Management, Expertise and Consumer Protection, from the Faculty of Business and Tourism from the Buchares t University of Economic Studies . The results of this research have shown an insufficient knowledge of Slow Food phenomenon and, especially, the Slow Food network activity in Romania. To show that the Slow Food type of food is a healthier option towards which the future consumer demand should be guided, especially those belonging to the younger generation, an antithetical comparative analysis of the nutritional value of two menus was performed: a suggestive one for the Slow Food feeding style and other one, specific to the fast food style. Slow Food style was considered antithetical to the fast food because many previous studies have shown a preference of the young for the fast-food type products, despite the

  20. Interneuron-mediated inhibition synchronizes neuronal activity during slow oscillation

    Science.gov (United States)

    Chen, Jen-Yung; Chauvette, Sylvain; Skorheim, Steven; Timofeev, Igor; Bazhenov, Maxim

    2012-01-01

    The signature of slow-wave sleep in the electroencephalogram (EEG) is large-amplitude fluctuation of the field potential, which reflects synchronous alternation of activity and silence across cortical neurons. While initiation of the active cortical states during sleep slow oscillation has been intensively studied, the biological mechanisms which drive the network transition from an active state to silence remain poorly understood. In the current study, using a combination of in vivo electrophysiology and thalamocortical network simulation, we explored the impact of intrinsic and synaptic inhibition on state transition during sleep slow oscillation. We found that in normal physiological conditions, synaptic inhibition controls the duration and the synchrony of active state termination. The decline of interneuron-mediated inhibition led to asynchronous downward transition across the cortical network and broke the regular slow oscillation pattern. Furthermore, in both in vivo experiment and computational modelling, we revealed that when the level of synaptic inhibition was reduced significantly, it led to a recovery of synchronized oscillations in the form of seizure-like bursting activity. In this condition, the fast active state termination was mediated by intrinsic hyperpolarizing conductances. Our study highlights the significance of both intrinsic and synaptic inhibition in manipulating sleep slow rhythms. PMID:22641778

  1. Slow and fast development in ladybirds: occurrence, effects and significance

    Directory of Open Access Journals (Sweden)

    G. Mishra

    2012-05-01

    Full Text Available Developmental and growth rates are known to vary in response to genetic, developmental, physiological and environmental factors. However, developmental variations that exist within a cohort under any constant rearing condition are not so well investigated. A few such prominent polymorphisms have been studied, but not the subtle ones. The current study investigates the presence of such varying rates of development, slow and fast, in a cohort reared under constant conditions in two ladybirds, Cheilomenes sexmaculata and Propylea dissecta. Our results reveal slow and fast developers in the cohorts of each species and the ratio of slow and fast developers was similar. Slow developers showed a female biased sex ratio. The two developmental variants differed significantly in juvenile duration only in the first instar and the pupal stage, though variations in developmental time were observed in all stages. Fecundity was higher in slow developers, but developmental rates did not affect egg viability. The similar ratio in both ladybirds indicates it to be a result of either presence of a constant ratio across species or an effect of the similar rearing environment.

  2. Optimal Curiosity-Driven Modular Incremental Slow Feature Analysis.

    Science.gov (United States)

    Kompella, Varun Raj; Luciw, Matthew; Stollenga, Marijn Frederik; Schmidhuber, Juergen

    2016-08-01

    Consider a self-motivated artificial agent who is exploring a complex environment. Part of the complexity is due to the raw high-dimensional sensory input streams, which the agent needs to make sense of. Such inputs can be compactly encoded through a variety of means; one of these is slow feature analysis (SFA). Slow features encode spatiotemporal regularities, which are information-rich explanatory factors (latent variables) underlying the high-dimensional input streams. In our previous work, we have shown how slow features can be learned incrementally, while the agent explores its world, and modularly, such that different sets of features are learned for different parts of the environment (since a single set of regularities does not explain everything). In what order should the agent explore the different parts of the environment? Following Schmidhuber's theory of artificial curiosity, the agent should always concentrate on the area where it can learn the easiest-to-learn set of features that it has not already learned. We formalize this learning problem and theoretically show that, using our model, called curiosity-driven modular incremental slow feature analysis, the agent on average will learn slow feature representations in order of increasing learning difficulty, under certain mild conditions. We provide experimental results to support the theoretical analysis.

  3. 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.

  4. 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.

  5. 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 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.

  6. 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...

  7. Slow light with electromagnetically induced transparency in cylindrical waveguide

    CERN Document Server

    Hatta, Agus Muhamad; Al-Hagan, Ola A; Moiseev, Sergey A

    2014-01-01

    Slow light with electromagnetically induced transparency (EIT) in the core of cylindrical waveguide (CW) for an optical fiber system containing three-level atoms is investigated. The CW modes are treated in the weakly guiding approximation which renders the analysis into manageable form. The transparency window and permittivity profile of the waveguide due to the strong pump field in the EIT scheme is calculated. For a specific permittivity profile of the waveguide due to EIT, the propagation constant of the weak signal field and spatial shape of fundamental guided mode are calculated by solving the vector wave equation using the finite difference method. It is found that the transparency window and slow light field can be controlled via the CW parameters. The reduced group velocity of slow light in this configuration is useful for many technological applications such as optical memories, effective control of single photon fields, optical buffer and delay line.

  8. 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...... an atomic and a quantum dot medium are discussed. Three generic schemes are compared, showing that only one of the schemes are viable for slow light in an inhomogeneously broadened medium. The principal differences between the schemes are analysed and discussed. Propagation calculations of the three schemes...... 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...

  9. 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.

  10. Modeling fast and slow earthquakes at various scales.

    Science.gov (United States)

    Ide, Satoshi

    2014-01-01

    Earthquake sources represent dynamic rupture within rocky materials at depth and often can be modeled as propagating shear slip controlled by friction laws. These laws provide boundary conditions on fault planes embedded in elastic media. Recent developments in observation networks, laboratory experiments, and methods of data analysis have expanded our knowledge of the physics of earthquakes. Newly discovered slow earthquakes are qualitatively different phenomena from ordinary fast earthquakes and provide independent information on slow deformation at depth. Many numerical simulations have been carried out to model both fast and slow earthquakes, but problems remain, especially with scaling laws. Some mechanisms are required to explain the power-law nature of earthquake rupture and the lack of characteristic length. Conceptual models that include a hierarchical structure over a wide range of scales would be helpful for characterizing diverse behavior in different seismic regions and for improving probabilistic forecasts of earthquakes.

  11. 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.

  12. Slow-roll corrections to inflaton fluctuations on a brane

    CERN Document Server

    Koyama, K; Wands, D; Koyama, Kazuya; Mizuno, Shuntaro; Wands, David

    2005-01-01

    Quantum fluctuations of an inflaton field, slow-rolling during inflation are coupled to metric fluctuations. In conventional four dimensional cosmology one can calculate the effect of scalar metric perturbations as slow-roll corrections to the evolution of a massless free field in de Sitter spacetime. This gives the well-known first-order corrections to the field perturbations after horizon-exit. If inflaton fluctuations on a four dimensional brane embedded in a five dimensional bulk spacetime are studied to first-order in slow-roll then we recover the usual conserved curvature perturbation on super-horizon scales. But on small scales, at high energies, we find that the coupling to the bulk metric perturbations cannot be neglected, leading to a modified amplitude of vacuum oscillations on small scales. This is a large effect which casts doubt on the reliability of the usual calculation of inflaton fluctuations on the brane neglecting their gravitational coupling.

  13. 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.

  14. 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.

  15. 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...

  16. 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.

  17. CARBOHYDRATE-CONTAINING COMPOUNDS WHICH BIND TO CARBOHYDRATE BINDING RECEPTORS

    DEFF Research Database (Denmark)

    1995-01-01

    Carbohydrate-containing compounds which contain saccharides or derivatives thereof and which bind to carbohydrate binding receptors are useful in pharmaceutical products for treatment of inflammatory diseases and other diseases.......Carbohydrate-containing compounds which contain saccharides or derivatives thereof and which bind to carbohydrate binding receptors are useful in pharmaceutical products for treatment of inflammatory diseases and other diseases....

  18. Moderate Cortical Cooling Eliminates Thalamocortical Silent States during Slow Oscillation.

    Science.gov (United States)

    Sheroziya, Maxim; Timofeev, Igor

    2015-09-23

    Reduction in temperature depolarizes neurons by a partial closure of potassium channels but decreases the vesicle release probability within synapses. Compared with cooling, neuromodulators produce qualitatively similar effects on intrinsic neuronal properties and synapses in the cortex. We used this similarity of neuronal action in ketamine-xylazine-anesthetized mice and non-anesthetized mice to manipulate the thalamocortical activity. We recorded cortical electroencephalogram/local field potential (LFP) activity and intracellular activities from the somatosensory thalamus in control conditions, during cortical cooling and on rewarming. In the deeply anesthetized mice, moderate cortical cooling was characterized by reversible disruption of the thalamocortical slow-wave pattern rhythmicity and the appearance of fast LFP spikes, with frequencies ranging from 6 to 9 Hz. These LFP spikes were correlated with the rhythmic IPSP activities recorded within the thalamic ventral posterior medial neurons and with depolarizing events in the posterior nucleus neurons. Similar cooling of the cortex during light anesthesia rapidly and reversibly eliminated thalamocortical silent states and evoked thalamocortical persistent activity; conversely, mild heating increased thalamocortical slow-wave rhythmicity. In the non-anesthetized head-restrained mice, cooling also prevented the generation of thalamocortical silent states. We conclude that moderate cortical cooling might be used to manipulate slow-wave network activity and induce neuromodulator-independent transition to activated states. Significance statement: In this study, we demonstrate that moderate local cortical cooling of lightly anesthetized or naturally sleeping mice disrupts thalamocortical slow oscillation and induces the activated local field potential pattern. Mild heating has the opposite effect; it increases the rhythmicity of thalamocortical slow oscillation. Our results demonstrate that slow oscillation can be

  19. 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.

  20. Slow effects of fast harmonic excitation for elastic structures

    DEFF Research Database (Denmark)

    Tcherniak, Dmitri; Thomsen, Jon Juel

    1998-01-01

    High-frequency excitation may affect the 'slow' behavior of a dynamical system. For example, equilibria may move, disappear, or gain or loose stability. We consider such slow effects of fast excitation for a simple mechanical system that incorporates features of many engineering structures. The s....... The study is intended to contribute to the general understanding of periodically excited linear and nonlinear systems, as well as to the current attempts to utilize high-frequency excitation for altering the low-frequency properties of structures....

  1. Closed-loop transcranial alternating current stimulation of slow oscillations

    Directory of Open Access Journals (Sweden)

    Wilde Christian

    2015-09-01

    Full Text Available Transcranial alternating current stimulation (tACS is an emerging non-invasive tool for modulating brain oscillations. There is evidence that weak oscillatory electrical stimulation during sleep can entrain cortical slow oscillations to improve the memory consolidation in rodents and humans. Using a novel method and a custom built stimulation device, automatic stimulation of slow oscillations in-phase with the endogenous activity in a real-time closed-loop setup is possible. Preliminary data from neuroplasticity experiments show a high detection performance of the proposed method, electrical measurements demonstrate the outstanding quality of the presented stimulation device.

  2. 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

  3. 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 Fitz...

  4. Optical signal processing using slow and fast light technologies

    DEFF Research Database (Denmark)

    Capmany, J.; Sales, Salvador; Xue, Weiqi;

    2009-01-01

    microwave or millimeter-wave frequency bands, we present one scheme to increase the achievable RF phase shift by enhancing light slow-down or speed-up. As a real application in microwave photonics, a widely tunable microwave photonic notch filter with 100% fractional tuning range is also proposed......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...

  5. Entangled photons from on-chip slow light

    CERN Document Server

    Takesue, Hiroki; Kuramochi, Eiichi; Notomi, Masaya

    2014-01-01

    We report the first entanglement generation experiment using an on-chip slow light device. With highly efficient spontaneous four-wave mixing enhanced by the slow light effect in a coupled resonator optical waveguide based on a silicon photonic crystal, we generated 1.5-$\\mu$m-band high-dimensional time-bin entangled photon pairs. We undertook two-photon interference experiments and observed the coincidence fringes with visibilities $>74\\%$. The present result enables us to realize an on-chip entanglement source with a very small footprint, which is an essential function for quantum information processing based on integrated quantum photonics.

  6. Past, Present and Future of Ultra-Slow Muons

    Science.gov (United States)

    Nagamine, Kanetada

    Experimental works towards a realization of the ultra-slow positive muon by laser resonant ionization of thermal muonium (USM) in 1995 are reviewed with reference to the other methods. Then a short description is given for the present USM project at J-PARC MUSE. Finally, possible future projects at J-PARC MUSE are presented, with a particular emphasis on the fundamental atomic physics of extreme muonic atomic states, µ+µ- atoms which would only be produced, along with the UCM, by a possible development of a slow and narrow µ- beam for which some ideas are given.

  7. 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.

  8. Slow Unfolding of Monomeric Proteins from Hyperthermophiles with Reversible Unfolding

    Directory of Open Access Journals (Sweden)

    Atsushi Mukaiyama

    2009-03-01

    Full Text Available Based on the differences in their optimal growth temperatures microorganisms can be classified into psychrophiles, mesophiles, thermophiles, and hyperthermophiles. Proteins from hyperthermophiles generally exhibit greater stability than those from other organisms. In this review, we collect data about the stability and folding of monomeric proteins from hyperthermophilies with reversible unfolding, from the equilibrium and kinetic aspects. The results indicate that slow unfolding is a general strategy by which proteins from hyperthermophiles adapt to higher temperatures. Hydrophobic interaction is one of the factors in the molecular mechanism of the slow unfolding of proteins from hyperthermophiles.

  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. 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

  11. Malnutrition and Mother-Infant Asynchrony: Slow Mental Development.

    Science.gov (United States)

    Ferreira, Maria Clotilde Rossetti

    1978-01-01

    Suggests an explanation for the link between environment, malnutrition, and rate of mental development in children. It is argued that biological factors and difficult socioeconomic conditions interact to slow mental development by undermining the establishment and maintenance of a "syntonic,""synchronic," and "reciprocal" relationship between the…

  12. 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.

  13. 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]…

  14. Slow light based on material and waveguide dispersion

    DEFF Research Database (Denmark)

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

    2009-01-01

    We study slow light pulse propagation in a photonic crystal structure consisting of a dispersive and absorptive dielectric material and compare it with the constant wave case. The group index and the trasmission are investigated for the example of an ensemble of semiconductor quantum dots embedded...

  15. Understanding bifurcation of slow versus fast cyber-attackers

    NARCIS (Netherlands)

    Wieren, van Maarten; Doerr, Christian; Jacobs, Vivian; Pieters, Wolter; Livraga, Giovanni; Torra, Vicenç; Aldini, Alessandro; Martinelli, Fabio; Suri, Neeraj

    2016-01-01

    Anecdotally, the distinction between fast “Smash-and-Grab” cyber-attacks on the one hand and slow attacks or “Advanced Persistent Threats” on the other hand is well known. In this article, we provide an explanation for this phenomenon as the outcome of an optimization from the perspective of the att

  16. A Model for the Sources of the Slow Solar Wind

    CERN Document Server

    Antiochos, S K; Titov, V S; Lionello, R; Linker, J A

    2011-01-01

    Models for the origin of the slow solar wind must account for two seemingly contradictory observations: The slow wind has the composition of the closed field corona, implying that it originates from the continuous opening and closing of flux at the boundary between open and closed field. On the other hand, the slow wind also has large angular width, up to ~ 60{\\circ}, suggesting that its source extends far from the open-closed boundary. We propose a model that can explain both observations. The key idea is that the source of the slow wind at the Sun is a network of narrow (possibly singular) open-field corridors that map to a web of separatrices and quasi-separatrix layers in the heliosphere. We compute analytically the topology of an open-field corridor and show that it produces a quasi-separatrix layer in the heliosphere that extends to angles far from the heliospheric current sheet. We then use an MHD code and MDI/SOHO observations of the photospheric magnetic field to calculate numerically, with high spat...

  17. 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...

  18. Slow Light by Two-Dimensional Photonic Crystal Waveguides

    Institute of Scientific and Technical Information of China (English)

    ZHANG Chao; HUANG Yan; MAO Xiao-Yu; CUI Kai-Yu; HUANG Yi-Dong; ZHANG Wei; PENG Jiang-De

    2009-01-01

    A simple and effective way to measure the group velocity of photonic crystal waveguides (PCWGs) is developed by using a fiber Mach-Zehnder interferometer. A PCWG with perfect air-bridge structure is fabricated and slow light with group velocity slower than c/80 is demonstrated.

  19. Slow ions in plasma wind tunnels. [satellite-ionosphere interaction

    Science.gov (United States)

    Oran, W. A.; Stone, N. H.; Samir, U.

    1976-01-01

    One of the limitations of simulation experiments for the study of interaction between a satellite and its space environment is the background of slow ions in the plasma chamber. These ions appear to be created by charge exchange between the beam ions and residual neutral gas and may affect measurements of the current and potential in the wake. Results are presented for a plasma wind tunnel experiment to study the effect of slow ions on both the ion and electron current distribution and the electron temperature in the wake of a body in a streaming plasma. It is shown that the effect of slow ions for beam ion density not exceeding 3 is not significant for measurements of ion current variations in the wake zone. This is not the case when studies are aimed at the quantitative examination of electron current and temperature variations in the near wake zone. In these instances, the measurements of electron properties in the wake should be done at very low system pressures or over a range of system pressures in order to ascertain the influence of slow ions.

  20. Post-error slowing in sequential action: An aging study

    Directory of Open Access Journals (Sweden)

    Marit eRuitenberg

    2014-02-01

    Full Text Available Previous studies demonstrated significant differences in the learning and performance of discrete movement sequences across the lifespan: Young adults (18-28 years showed more indications for the development of (implicit motor chunks and explicit sequence knowledge than middle-aged (55-62 years; Verwey et al., 2011 and elderly participants (75-88 years; Verwey, 2010. Still, even in the absence of indications for motor chunks, the middle-aged and elderly participants showed some performance improvement too. This was attributed to a sequence learning mechanism in which individual reactions are primed by implicit sequential knowledge. The present work further examined sequential movement skill across these age groups. We explored the consequences of making an error on the execution of a subsequent sequence, and investigated whether this is modulated by aging. To that end, we re-analyzed the data from our previous studies. Results demonstrate that sequencing performance is slowed after an error has been made in the previous sequence. Importantly, for young adults and middle-aged participants the observed slowing was also accompanied by increased accuracy after an error. We suggest that slowing in these age groups involves both functional and non-functional components, while slowing in elderly participants is non-functional. Moreover, using action sequences (instead of single key-presses may allow to better track the effects on performance of making an error.

  1. Slow motions in systems with fast modulated excitation

    Science.gov (United States)

    Kremer, E.

    2016-11-01

    It is well known that high-frequency excitation can modify the behavior of systems with respect to slow motions. The goal of this study is consideration of these effects in a rather general case of analytical systems with modulated sinusoidal excitation. The method of direct separation of motions proposed by I.I. Blekhman was applied in a modified form with the explicit introduction of a small parameter. Equations for the slow motions are obtained and an analysis of how they depend on the structure of the original equations is performed. Five basic effects corresponding to different possible dependencies of the modulation amplitude on position, velocity, and slow time are selected (some of them for the first time). These effects offer a possibility for designing a high-frequency control of the slow motions with specified properties. For example, high-frequency excitation in a system with a nonlinear friction can essentially increase the effective damping. The results are also of significance for system identification and diagnostics. Analysis of a hydraulic valve is given as an example of application.

  2. 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.

  3. A Model for the Sources of the Slow Solar Wind

    Science.gov (United States)

    Antiochos, Spiro K.; Mikic, Z.; Lionello, R.; Titov, V.; Linker, J.

    2010-05-01

    Models for the origin of the slow solar wind must account for two seemingly contradictory observations: The slow wind has the composition of the closed-field corona, implying that it originates at the open-closed field boundary layer, but it also has large angular width, up to 40 degrees. We propose a model that can explain both observations. The key idea is that the source of the slow wind at the Sun is a network of narrow (possibly singular) open-field corridors that map to a web of separatrices and quasi-separatrix layers in the heliosphere. We calculate with high numerical resolution, the quasi-steady solar wind and magnetic field for a Carrington rotation centered about the August 1, 2008 total solar eclipse. Our numerical results demonstrate that, at least for this time period, a web of separatrices (S-web) forms with sufficient density and extent in the heliosphere to account for the observed properties of the slow wind. We discuss the implications of our S-web model for the structure and dynamics of the corona and heliosphere, and propose further tests of the model. This work was supported, in part, by the NASA HTP, TR&T and SR&T programs.

  4. Human Growth Hormone (HGH): Does It Slow Aging?

    Science.gov (United States)

    Healthy Lifestyle Healthy aging Human growth hormone is described by some as the key to slowing the aging process. Before you sign up, get the facts. ... stave off some of the changes linked to aging, such as decreased muscle and bone mass. If ...

  5. 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...

  6. Tropical birds have a slow pace of life.

    Science.gov (United States)

    Wiersma, Popko; Muñoz-Garcia, Agustí; Walker, Amy; Williams, Joseph B

    2007-05-29

    Tropical birds are relatively long-lived and produce few offspring, which develop slowly and mature relatively late in life, the slow end of the life-history axis, whereas temperate birds lie at the opposite end of this continuum. We tested the hypothesis that tropical birds have evolved a reduced basal metabolic rate (BMR). We measured BMR of 69 species of tropical birds, the largest data set amassed on metabolic rates of tropical birds, and compared these measurements with 59 estimates of BMR for temperate birds. Our analyses included conventional least squares regression, regressions based on phylogenetic independent contrasts, and a comparison of BMR of 13 phylogenetically matched pairs, one species from the tropics and one from northerly temperate areas. Our triptych showed that tropical birds had a reduced BMR, compelling evidence for a connection between the life history of tropical birds and a slow pace of life. Further, tropical migrants breeding in temperate habitats had a lower BMR than did temperate residents, suggesting that these migrants have physiological traits consistent with a slow pace of life. In addition, we determined that tropical birds had a lower cold-induced peak metabolic rate and thermogenic metabolic scope than temperate species, a finding that is consistent with the hypothesis that their environment has not selected for high levels of thermogenesis, or alternatively, that a slow pace of life may be incompatible with high thermogenic capacity. We conclude that physiological function correlates with the suite of life-history traits.

  7. 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.

  8. Good cash flow = come in fast, go out slow!

    Science.gov (United States)

    Garvey, Sherill

    2002-07-01

    The formula for successful cash management in home care is a simple one: The agency must bring cash in as quickly as possible, while keeping expenditures at as low and slow a pace as possible. However, while the formula may be simple, success may be elusive unless agency administrators have a well-thought-out plan to handle cash management.

  9. 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.

  10. 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

  11. Laser cooling and slowing of CaF molecules

    Science.gov (United States)

    Truppe, Stefan; Williams, Hannah; Hambach, Moritz; Sauer, Ben; Hinds, Ed; Tarbutt, Mike

    2016-05-01

    We have developed a cold and bright source for CaF molecules and use laser radiation pressure to slow the molecules to within the capture velocity of a magneto-optical trap (MOT). Using laser ablation of Ca into a continuous flow of cryogenic Helium buffer gas mixed with SF6 we produce up to 1011 molecules per steradian per pulse in a single rotational state. The molecules move with a mean forward velocity of 160m/s and have a velocity spread of 80m/s. We then apply laser radiation pressure to the molecular beam to slow and cool the molecules. We form a quasi-closed laser-cooling cycle by using a main cooling laser to drive the B2Σ+ (v' = 0) - X2Σ+ (v'' = 0) transition and a single repump laser to address the A2Π1 / 2 (v' = 0) -X2Σ+ (v'' = 1) transition. Radio-frequency sidebands applied to both lasers address the hyperfine structure. By chirping the frequencies of both lasers to keep the decelerating molecules resonant with the light, we scatter more than 10000 photons and reduce the speed to below 50 m/s. We achieve a similar effect by broadening the linewidth of the laser to several hundred MHz. This ``white-light'' slowing is compared to the chirped slowing technique. We also present progress towards a MOT of CaF molecules.

  12. Efficient coupling to slow light photonic crystal waveguide

    Science.gov (United States)

    Khan, Md Shofiqul Islam; Devarapu, Ganga Chinna Rao; O'Faolain, Liam

    2016-04-01

    Slow light photonic crystal waveguides (PCWs) have been the subject of intensive study due to their potential for on-chip applications such as optical buffers and the enhancement of nonlinear phenomenon. However, due to high group velocity mismatch between the strip waveguide and the slow light waveguide efficient coupling of light is challenging. The coupling efficiency is also very sensitive to the truncation at the interface between the two waveguides. This sensitivity can be removed and light can efficiently be coupled from the strip waveguide to the slow light waveguide by adding an intermediate photonic crystal waveguide (or coupler) that operates at a group index of ˜ 5. Several designs have been proposed for couplers to obtain higher coupling efficiency within the desired group index range. We have studied uniaxial stretched couplers in which the lattice constant is stretched in the direction of propagation by 10-50 nm in the coupler region. Using a Finite Difference Time Domain (FDTD) Simulation Method that allows the extraction of the group index, we have observed 8.5 dB improvement in the coupling efficiency at the group index of 30. Efficient coupling is dominantly determined by the band edge position of the coupler region and maximum transmission efficiency is limited by the maximum transmission of the coupler PCW. If the band edge of coupler PCW is sufficiently red shifted relative to the band edge of the slow light PCW then higher coupling efficiency can be achieved.

  13. Structural looseness investigation in slow rotating permanent magnet generators

    DEFF Research Database (Denmark)

    Skrimpas, Georgios Alexandros; Mijatovic, Nenad; Sweeney, Christian Walsted;

    2016-01-01

    Structural looseness in electric machines is a condition influencing the alignment of the machine and thus the overall bearing health. In this work, assessment of the above mentioned failure mode is tested on a slow rotating (running speed equal to 0.7Hz) permanent magnet generator (PMG), while...

  14. 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…

  15. The multilayer Fe/Hf studied with slow positron beam

    Science.gov (United States)

    Murashige, Y.; Tashiro, M.; Nakajyo, T.; Koizumi, T.; Kanazawa, I.; Komori, F.; Ito, Y.

    1997-04-01

    The positron annihilation parameter versus the incident positron energy is measured in the thin Fe films and the Fe/Hf bilayer on silica substrate, by means of the variable energetic slow-positron beam technique. We have analyzed the change in open-volume spaces and vacancy-type defects among the Fe microcrystals in these thin films with the deposition temperature.

  16. 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...

  17. 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…

  18. Grating-assisted superresolution of slow waves in Fourier space

    DEFF Research Database (Denmark)

    Thomas, N. Le; Houdré, R.; Frandsen, Lars Hagedorn

    2007-01-01

    with a high numerical aperture Fourier space imaging set-up. A high-resolution spectroscopy of the far-field emission diagram allows us to accurately and efficiently determine the dispersion curve and the group-index dispersion of planar photonic waveguides operating in the slow light regime....

  19. A Model fot the Sources of the Slow Solar Wind

    Science.gov (United States)

    Antiochos, S. K.; Mikic, Z.; Titov, V. S.; Lionello, R.; Linker, J. A.

    2011-01-01

    Models for the origin of the slow solar wind must account for two seemingly contradictory observations: the slow wind has the composition of the closed-field corona, implying that it originates from the continuous opening and closing of flux at the boundary between open and closed field. On the other hand, the slow wind also has large angular width, up to approx.60deg, suggesting that its source extends far from the open-closed boundary. We propose a model that can explain both observations. The key idea is that the source of the slow wind at the Sun is a network of narrow (possibly singular) open-field corridors that map to a web of separatrices and quasi-separatrix layers in the heliosphere. We compute analytically the topology of an open-field corridor and show that it produces a quasi-separatrix layer in the heliosphere that extends to angles far from the heliospheric current sheet. We then use an MHD code and MDI/SOHO observations of the photospheric magnetic field to calculate numerically, with high spatial resolution, the quasi-steady solar wind, and magnetic field for a time period preceding the 2008 August 1 total solar eclipse. Our numerical results imply that, at least for this time period, a web of separatrices (which we term an S-web) forms with sufficient density and extent in the heliosphere to account for the observed properties of the slow wind. We discuss the implications of our S-web model for the structure and dynamics of the corona and heliosphere and propose further tests of the model. Key words: solar wind - Sun: corona - Sun: magnetic topology

  20. A Model for the Sources of the Slow Solar Wind

    Science.gov (United States)

    Antiochos, Spiro K.; Mikic, Z.; Titov, V. S.; Lionello, R.; Linker, J. A.

    2010-01-01

    Models for the origin of the slow solar wind must account for two seemingly contradictory observations: The slow wind has the composition of the closed-field corona, implying that it originates from the continuous opening and closing of flux at the boundary between open and closed field. On the other hand, the slow wind has large angular width, up to approximately 60 degrees, suggesting that its source extends far from the open-closed boundary. We propose a model that can explain both observations. The key idea is that the source of the slow wind at the Sun is a network of narrow (possibly singular) open-field corridors that map to a web of separatrices and quasi-separatrix layers in the heliosphere. We compute analytically the topology of an open-field corridor and show that it produces a quasi-separatrix layer in the heliosphere that extends to angles far front the heliospheric current sheet. We then use an MHD code and MIDI/SOHO observations of the photospheric magnetic field to calculate numerically, with high spatial resolution, the quasi-steady solar wind and magnetic field for a time period preceding the August 1, 2008 total solar eclipse. Our numerical results imply that, at least for this time period, a web of separatrices (which we term an S-web) forms with sufficient density and extent in the heliosphere to account for the observed properties of the slow wind. We discuss the implications of our S-web model for the structure and dynamics of the corona and heliosphere, and propose further tests of the model.

  1. Terms of Binding

    NARCIS (Netherlands)

    Sevcenco, A.

    2006-01-01

    The present dissertation aimed at achieving two goals. First, it constitutes an attempt to widen the search for phenomena that bear relevance to the idea that binding has a syntactic residue and is not, therefore, an exclusively semantic matter. Second, it tried to provide the technical means to acc

  2. Binding and Bulgarian

    NARCIS (Netherlands)

    Schürcks-Grozeva, Lilia Lubomirova

    2003-01-01

    In haar proefschrift analyseert Lilia Schürcks de anaforische verschijnselen in de Bulgaarse taal. Het gaat dan om wederkerende aspecten, uitgedrukt bij woorden als ‘zich’ en ‘elkaar’. De situatie in het Bulgaars blijkt moeilijk in te passen in de klassieke Binding Theory van Noam Chomsky. Bron: RUG

  3. MD-2 binds cholesterol.

    Science.gov (United States)

    Choi, Soo-Ho; Kim, Jungsu; Gonen, Ayelet; Viriyakosol, Suganya; Miller, Yury I

    2016-02-19

    Cholesterol is a structural component of cellular membranes, which is transported from liver to peripheral cells in the form of cholesterol esters (CE), residing in the hydrophobic core of low-density lipoprotein. Oxidized CE (OxCE) is often found in plasma and in atherosclerotic lesions of subjects with cardiovascular disease. Our earlier studies have demonstrated that OxCE activates inflammatory responses in macrophages via toll-like receptor-4 (TLR4). Here we demonstrate that cholesterol binds to myeloid differentiation-2 (MD-2), a TLR4 ancillary molecule, which is a binding receptor for bacterial lipopolysaccharide (LPS) and is indispensable for LPS-induced TLR4 dimerization and signaling. Cholesterol binding to MD-2 was competed by LPS and by OxCE-modified BSA. Furthermore, soluble MD-2 in human plasma and MD-2 in mouse atherosclerotic lesions carried cholesterol, the finding supporting the biological significance of MD-2 cholesterol binding. These results help understand the molecular basis of TLR4 activation by OxCE and mechanisms of chronic inflammation in atherosclerosis.

  4. 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.

  5. Cellulose binding domain proteins

    Science.gov (United States)

    Shoseyov, Oded; Shpiegl, Itai; Goldstein, Marc; Doi, Roy

    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.

  6. 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.

  7. 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.

  8. 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...

  9. Slow inactivation of Na+ current and slow cumulative spike adaptation in mouse and guinea-pig neocortical neurones in slices.

    Science.gov (United States)

    Fleidervish, I A; Friedman, A; Gutnick, M J

    1996-05-15

    1. Spike adaptation of neocortical pyramidal neurones was studied with sharp electrode recordings in slices of guinea-pig parietal cortex and whole-cell patch recordings of mouse somatosensory cortex. Repetitive intracellular stimulation with 1 s depolarizing pulses delivered at intervals of pS and an extrapolated reversal potential of 127 +/- 6 mV above resting potential (Vr) (mean +/- S.E.M.; n = 5). Vr was estimated at -72 +/- 3 mV (n = 8), based on the voltage dependence of the steady-state inactivation (h infinity) curve. 5. Slow inactivation (SI) of Na+ channels had a mono-exponential onset with tau on between 0.86 and 2.33 s (n = 3). Steady-state SI was half-maximal at -43.8 mV and had a slope of 14.4 mV (e-fold)-1. Recovery from a 2 s conditioning pulse was bi-exponential and voltage dependent; the slow time constant ranged between 0.45 and 2.5 s at voltages between-128 and -68 mV. 6. The experimentally determined parameters of SI were adequate to simulate slow cumulative adaptation of spike firing in a single-compartment computer model. 7. Persistent Na+ current, which was recorded in whole-cell configuration during slow voltage ramps (35 mV s-1), also underwent pronounced SI, which was apparent when the ramp was preceded by a prolonged depolarizing pulse.

  10. 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…

  11. Slow wave activity and slow oscillations in sleepwalkers and controls: effects of 38 h of sleep deprivation.

    Science.gov (United States)

    Perrault, Rosemarie; Carrier, Julie; Desautels, Alex; Montplaisir, Jacques; Zadra, Antonio

    2013-08-01

    Sleepwalkers have been shown to have an unusually high number of arousals from slow wave sleep and lower slow wave activity (SWA) power during the night than controls. Because sleep deprivation increases the frequency of slow wave sleep (SWS) arousals in sleepwalkers, it may also affect the expression of the homeostatic process to a greater extent than shown previously. We thus investigated SWA power as well as slow wave oscillation (SWO) density in 10 sleepwalkers and nine controls at baseline and following 38 h of sleep deprivation. There was a significant increase in SWA during participants' recovery sleep, especially during their second non-rapid eye movement (NREM) period. SWO density was similarly increased during recovery sleep's first two NREM periods. A fronto-central gradient in SWA and SWO was also present on both nights. However, no group differences were noted on any of the 2 nights on SWA or SWO. This unexpected result may be related to the heterogeneity of sleepwalkers as a population, as well as our small sample size. SWA pressure after extended sleep deprivation may also result in a ceiling effect in both sleepwalkers and controls.

  12. 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.

  13. G protein-cAMP signaling pathway mediated by PGA3 plays different roles in regulating the expressions of amylases and cellulases in Penicillium decumbens.

    Science.gov (United States)

    Hu, Yibo; Liu, Guodong; Li, Zhonghai; Qin, Yuqi; Qu, Yinbo; Song, Xin

    2013-01-01

    Heterotrimeric G proteins (G proteins) have been extensively investigated for their regulatory functions in morphogenesis and development in filamentous fungi. In addition, G proteins were also shown to be involved in the regulation of cellulase expression in some fungi. Here, we report the different regulatory effects of PGA3, a group III G protein α subunit, on the expressions of amylases and cellulases in Penicillium decumbens. Deletion of pga3 resulted in impaired amylase production and significantly decreased transcription of the major amylase gene amy15A. Supplementation of exogenous cAMP or its analog dibutyryl-cAMP restored amylase production in Δpga3 strain, suggesting an essential role of PGA3 in amylase synthesis via controlling cAMP level. On the other hand, the transcription of major cellulase gene cel7A-2 increased, nevertheless cellulase activity in the medium was not affected, in Δpga3. The above regulatory effects of PGA3 are carbon source-independent, and are achieved, at least, by cAMP-mediated regulation of the expression level of transcription factor AmyR. The functions of PGA3 revealed by gene deletion were partially supported by the analysis of the mutant carrying dominantly-activated PGA3. The results provided new insights into the understanding of the physiological functions of G protein-cAMP pathway in filamentous fungi.

  14. 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.

  15. Cellular inhibitors of apoptosis proteins cIAP1 and cIAP2 are required for efficient caspase-1 activation by the inflammasome.

    Science.gov (United States)

    Labbé, Katherine; McIntire, Christian R; Doiron, Karine; Leblanc, Philippe M; Saleh, Maya

    2011-12-23

    Pathogen and danger recognition by the inflammasome activates inflammatory caspases that mediate inflammation and cell death. The cellular inhibitor of apoptosis proteins (cIAPs) function in apoptosis and innate immunity, but their role in modulating the inflammasome and the inflammatory caspases is unknown. Here we report that the cIAPs are critical effectors of the inflammasome and are required for efficient caspase-1 activation. cIAP1, cIAP2, and the adaptor protein TRAF2 interacted with caspase-1-containing complexes and mediated the activating nondegradative K63-linked polyubiquitination of caspase-1. Deficiency in cIAP1 (encoded by Birc2) or cIAP2 (Birc3) impaired caspase-1 activation after spontaneous or agonist-induced inflammasome assembly, and Birc2(-/-) or Birc3(-/-) mice or mice administered with an IAP antagonist had a dampened response to inflammasome agonists and were resistant to peritonitis. Our results describe a role for the cIAPs in innate immunity and further demonstrate the evolutionary conservation between cell death and inflammation mechanisms.

  16. 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.

  17. 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.

  18. 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.

  19. 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....

  20. Standing Slow MHD Waves in Radiatively Cooling Coronal Loops

    CERN Document Server

    Al-Ghafri, Khalil Salim

    2015-01-01

    The standing slow magneto-acoustic oscillations in cooling coronal loops are investigated. There are two damping mechanisms which are considered to generate the standing acoustic modes in coronal magnetic loops namely thermal conduction and radiation. The background temperature is assumed to change temporally due to optically thin radiation. In particular, the background plasma is assumed to be radiatively cooling. The effects of cooling on longitudinal slow MHD modes is analytically evaluated by choosing a simple form of radiative function that ensures the temperature evolution of the background plasma due to radiation coincides with the observed cooling profile of coronal loops. The assumption of low-beta plasma leads to neglect the magnetic field perturbation and eventually reduces the MHD equations to a 1D system modelling longitudinal MHD oscillations in a cooling coronal loop. The cooling is assumed to occur on a characteristic time scale much larger than the oscillation period that subsequently enables...

  1. 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.

  2. 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...

  3. 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.

  4. Systematic design of loss-engineered slow-light waveguides

    DEFF Research Database (Denmark)

    Wang, Fengwen; Jensen, Jakob Søndergaard; Mørk, Jesper;

    2012-01-01

    This paper employs topology optimization to systematically design free-topology loss-engineered slow-light waveguides with enlarged group index bandwidth product (GBP). The propagation losses of guided modes are evaluated by the imaginary part of eigenvalues in complex band structure calculations......, where the scattering losses due to manufacturing imperfections are represented by an edge-related effective dissipation. The loss engineering of slow-light waveguides is realized by minimizing the propagation losses of design modes. Numerical examples illustrate that the propagation losses of free......-topology dispersion-engineered waveguides can be significantly suppressed by loss engineering. Comparisons between fixed- and free-topology loss-engineered waveguides demonstrate that the GBP can be enhanced significantly by the free-topology loss-engineered waveguides with a small increase of the propagation losses....

  5. Laser radiation pressure slowing of a molecular beam

    CERN Document Server

    Barry, J F; Norrgard, E B; DeMille, D

    2011-01-01

    There is substantial interest in producing samples of ultracold molecules for possible applications in quantum computation, quantum simulation of condensed matter systems, precision measurements, controlled chemistry, and high precision spectroscopy. A crucial step to obtaining large samples of ultracold, trapped molecules is developing a means to bridge the gap between typical molecular source velocities (~150-600 m/s) and velocities for which trap loading or confinement is possible (~5-20 m/s). Here we show deceleration of a beam of neutral strontium monofluoride (SrF) molecules using radiative force. Under certain conditions, the deceleration results in a substantial flux of molecules with velocities <50 m/s. The observed slowing, from ~140 m/s, corresponds to scattering ~10000 photons. We also observe longitudinal velocity compression under different conditions. Combined with molecular laser cooling techniques, this lays the groundwork to create slow and cold molecular beams suitable for trap loading.

  6. 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...

  7. Passive integrated circuits utilizing slow light in photonic crystal waveguides

    DEFF Research Database (Denmark)

    Lavrinenko, Andrei; Têtu, Amélie; Yang, Lirong;

    2006-01-01

    We report thorough investigations of photonic crystal waveguide properties in the slow light regime. The transmission and the group index near the cutoff wavelengths oscillate in phase in close analogy with the ID photonic crystal behavior. The influence of having a finite number of periods...... in the photonic crystal waveguide is addressed to explain the spiky character of both the transmission and group index spectra. The profile of the slow-light modes is stretched out into the first and second rows of the holes closest to the waveguide channel. One of our strategies to ameliorate the design...... of photonic crystal devices is to engineer the radii of holes in these rows. A topology optimization approach is also utilized to make further improvements. The results of the numerical simulations and the optical characterization of fabricated devices such as straight waveguides with bends and couplers...

  8. 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...

  9. 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.

  10. 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.

  11. Cascaded passive silicon microrings for large bandwidth slow light device

    Energy Technology Data Exchange (ETDEWEB)

    Li Yuntao; Hu Yingtao; Xiao Xi; Li Zhiyong; Yu Yude; Yu Jinzhong, E-mail: ytli@semi.ac.cn [State Key Laboratory of integrated Optoelectronics, Institute of Semiconductors, Chinese Academy of Sciences, P. O. Box 912, Beijing 100083 (China)

    2011-02-01

    Slow light devices have important applications in the areas of data buffering, signal processing, and phased array antenna. Cascaded microring resonators structure can obtain large delay and also enhance the bandwidth, which was considered as a potential approach for future on-chip optical buffer. In this paper, we demonstrated a large bandwidth slow light device using cascaded Silicon-on-insulator (SOI) based microring resonators. With carefully designed the gap between the bus and the ring waveguides and the distances between the adjacent rings, a 57 ps group delay was observed and 83 Gbps maximum allowable bit rate is suggested according the measured 3 dB spectral bandwidth in the 8-stage cascaded microrings.

  12. Nonlinear light propagation in chalcogenide photonic crystal slow light waveguides.

    Science.gov (United States)

    Suzuki, Keijiro; Baba, Toshihiko

    2010-12-06

    Optical nonlinearity can be enhanced by the combination of highly nonlinear chalcogenide glass and photonic crystal waveguides (PCWs) providing strong optical confinement and slow-light effects. In a Ag-As(2)Se(3) chalcogenide PCW, the effective nonlinear parameter γeff reaches 6.3 × 10(4) W(-1)m(-1), which is 200 times larger than that in Si photonic wire waveguides. In this paper, we report the detailed design, fabrication process, and the linear and nonlinear characteristics of this waveguide at silica fiber communication wavelengths. We show that the waveguide exhibits negligible two-photon absorption, and also high-efficiency self-phase modulation and four-wave mixing, which are assisted by low-dispersion slow light.

  13. Slow digestion properties of rice different in resistant starch.

    Science.gov (United States)

    Shu, Xiaoli; Jia, Limeng; Ye, Hongxia; Li, Chengdao; Wu, Dianxing

    2009-08-26

    The hydrolysis of starch is a key factor for controlling the glycemic index (GI). Slow digestion properties of starch lead to slower glucose release and lower glycemic response. Food with high resistant starch (RS) possesses great value for controlling the GI. To elucidate the factors that play a role in slow digestibility, seven rice mutants different in RS contents were selected for comparative studies. The degree of hydrolysis showed highly significant correlation with RS, apparent amylose content (AAC), lipid content (LC), and other starch physiochemical properties in all these materials with different RS contents. The rate of in vitro digestible starch correlated positively with RS, whereas digestibility was affected mostly by lipid content for those mutants with similar RS. Starch-lipid complexes and short chains with degrees of polymerization (DP) of 8-12 strongly influenced starch digestion. The integrity of aggregated starch and the number of round starch granules might influence the digestibility of starch directly.

  14. Primordial perturbations from slow-roll inflation on a brane

    CERN Document Server

    Koyama, K; Mennim, A; Rubakov, V A; Wands, D; Hiramatsu, Takashi; Koyama, Kazuya; Mennim, Andrew; Wands, David

    2007-01-01

    In this paper we quantise scalar perturbations in a Randall-Sundrum-type model of inflation where the inflaton field is confined to a single brane embedded in five-dimensional anti-de Sitter space-time. In the high energy regime, small-scale inflaton fluctuations are strongly coupled to metric perturbations in the bulk and gravitational back-reaction has a dramatic effect on the behaviour of inflaton perturbations on sub-horizon scales. This is in contrast to the standard four-dimensional result where gravitational back-reaction can be neglected on small scales. Nevertheless, this does not give rise to significant particle production, and the correction to the power spectrum of the curvature perturbations on super-horizon scales is shown to be suppressed by a slow-roll parameter. We calculate the complete first order slow-roll corrections to the spectrum of primordial curvature perturbations.

  15. An exact solution of the slow-light problem

    CERN Document Server

    Rybin, A V; Bishop, A R

    2004-01-01

    We investigate propagation of a slow-light soliton in atomic vapors and Bose-Einstein condensates described by the nonlinear Lambda-model. We show that the group velocity of the soliton monotonically decreases with the intensity of the controlling laser field, which decays exponentially after the laser is switched off. The shock wave of the vanishing controlling field overtakes the slow soliton and stops it, while the optical information is recorded in the medium in the form of spatially localized polarization. We find an explicit exact solution describing the whole process within the slowly varying amplitude and phase approximation. Our results point to the possibility of addressing spatially localized memory formations and moving these memory bits along the medium in a controllable fashion.

  16. The Asteroid Catalog Using AKARI IRC Slow-Scan Observations

    CERN Document Server

    Hasegawa, Sunao; Kuroda, Daisuke; Takita, Satoshi; Usui, Fumihiko

    2012-01-01

    We present an asteroidal catalog from the mid-infrared wavelength region using the slow-scan observation mode obtained by the Infrared Camera (IRC) on-board the Japanese infrared satellite AKARI. An archive of IRC slow-scan observations comprising about 1000 images was used to search for serendipitous encounters of known asteroids. We have determined the geometric albedos and diameters for 88 main-belt asteroids, including two asteroids in the Hilda region, and compared these, where possible, with previously published values. Approximately one-third of the acquired data reflects new asteroidal information. Some bodies classified as C or D-type with high albedo were also identified in the catalog.

  17. 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...

  18. Sagnac Interferometry in a Slow-Light Medium

    CERN Document Server

    Purves, G T; Hughes, I G; Adams, Charles S.; Hughes, Ifan G.; Purves, Graham T.

    2005-01-01

    We use a Sagnac interferometer to measure the dispersive and absorptive properties of room temperature Rubidium vapor on the D_2 line at 780.2 nm. We apply a pump beam such that the resulting Lambda system exhibits Electromagnetically Induced Transparency. Using a "biased alignment" technique we demonstrate a direct and robust method of measuring the rapid variation in the refractive index. Such a "slow-light" Sagnac interferometer is ideally suited to precision measurement applications such as magnetometry and inertial sensing.

  19. Using Nonuniform Fiber to Generate Slow Light via SBS

    Directory of Open Access Journals (Sweden)

    Wenhai Li

    2008-01-01

    Full Text Available The data pulse delay based on slow light induced by stimulated Brillouin scattering (SBS in a nonuniform dispersion decreasing fiber (DDF is demonstrated experimentally, and the distortions of data pulses at different beat frequencies are studied. We found that a delay exceeding a pulse width can be achieved at particular beat frequency, and the DDF has larger delay versus gain slope coefficient with much better output pulse quality than single-mode fiber.

  20. Dirac-graphene quasiparticles in strong slow-light pulse

    Science.gov (United States)

    Golovinski, P. A.; Astapenko, V. A.; Yakovets, A. V.

    2017-02-01

    An analytical Volkov's solution of the massless Dirac equation for graphene in the field of slow-light pulse with arbitrary time dependence is obtained. Exact solutions are presented for special cases of monochromatic field and a single-cycle pulse. Following the Fock-Schwinger proper time method, the Green's function for quasiparticles is derived with the account of the influence an external classical electromagnetic wave field.

  1. The puzzle of decreased homeostatic slow wave sleep in aging

    OpenAIRE

    Rytkönen, Kirsi-Marja

    2012-01-01

    Slow wave sleep is the most important part of sleep, yet it decreases with aging. Staying awake puts pressure on the neurons of the brain s arousal systems, e.g. on the cortically projecting neurons of the basal forebrain. During wakefulness, these neurons are active and excite the cortex, thereby enhancing behavioral arousal. Sleep quality and duration are compromised with increasing age. Elderly people often experience these symptoms as sleep problems and contact medical professionals. Trea...

  2. Slow Wave Characteristics of Helix Structure with Elliptical Cross Section

    Institute of Scientific and Technical Information of China (English)

    XIE Jian-Xiang; WEI Yan-Yu; GONG Yu-Bin; Fu Cheng-Fang; YUE Ling-Na; WANG Wen-Xiang

    2007-01-01

    We present a novel helix slow wave structure with an elliptical cross section shielded by an elliptical waveguide.The rf characteristics including dispersion properties,interaction impedance of zero mode in this structure have been studied in detail.The theoretical results reveal that weaker dispersion even abnormal dispersion characteristics is obtained with the increasing eccentricity of the elliptical waveguide,while the interaction impedance is enhanced by enlarging the eccentricity of elliptical helix.

  3. [Chronic and slow neuroinfections. Current status of problem].

    Science.gov (United States)

    Antonov, P V; Tsinzerling, V A

    2001-01-01

    Some causes and conditions of chronic and slow neuroinfections were reviewed: brain immunological "priveledge"; congenital immunodeficiencies including clinically latent; immunomodulation induced by microorganisms due to infection of immune cells, inactivation of cytokines making difficulties to antibodies; disorders of genetic control of immune reaction; immunopathologic processes are of great importance for the agents persistence including autoimmunity. Microorganisms can locate in the neurons, glyocytes, endothelium. Neuroinfections chronic course depends on the agents properties and peculiarities of nervous system reactivity.

  4. Slow control systems of the Reactor Experiment for Neutrino Oscillation

    Energy Technology Data Exchange (ETDEWEB)

    Choi, J.H. [Basic Science Research Institute, Dongshin University, Naju 58245 (Korea, Republic of); Jang, H.I. [Department of Fire Safety, Seoyeong University, Gwangju 61268 (Korea, Republic of); Choi, W.Q. [Department of Physics & Astronomy, Seoul National University, Seoul 08826 (Korea, Republic of); Choi, Y. [Department of Physics, Sungkyunkwan University, Suwon 16419 (Korea, Republic of); Jang, J.S. [GIST College, Gwangju Institute of Science and Technology, Gwangju 61005 (Korea, Republic of); Jeon, E.J. [Institute for Basic Science, Daejeon 34047 (Korea, Republic of); Department of Physics and Astronomy, Sejong University, Seoul 05006 (Korea, Republic of); Joo, K.K.; Kim, B.R. [Institute for Universe & Elementary Particles, Chonnam National University, Gwangju 61186 (Korea, Republic of); Kim, H.S. [Department of Physics and Astronomy, Sejong University, Seoul 05006 (Korea, Republic of); Kim, J.Y. [Institute for Universe & Elementary Particles, Chonnam National University, Gwangju 61186 (Korea, Republic of); Kim, S.B.; Kim, S.Y. [Department of Physics & Astronomy, Seoul National University, Seoul 08826 (Korea, Republic of); Kim, W. [Department of Physics, Kyungpook National University, Daegu 41566 (Korea, Republic of); Kim, Y.D. [Institute for Basic Science, Daejeon 34047 (Korea, Republic of); Ko, Y.J. [Department of Physics, Chung-Ang University, Seoul 06974 (Korea, Republic of); Lee, J.K. [Department of Physics & Astronomy, Seoul National University, Seoul 08826 (Korea, Republic of); Lim, I.T. [Institute for Universe & Elementary Particles, Chonnam National University, Gwangju 61186 (Korea, Republic of); Pac, M.Y., E-mail: pac@dsu.kr [Basic Science Research Institute, Dongshin University, Naju 58245 (Korea, Republic of); Park, I.G. [Department of Physics, Gyeongsang National University, Jinju 52828 (Korea, Republic of); Park, J.S. [Department of Physics & Astronomy, Seoul National University, Seoul 08826 (Korea, Republic of); and others

    2016-02-21

    The RENO experiment has been in operation since August 2011 to measure reactor antineutrino disappearance using identical near and far detectors. For accurate measurements of neutrino mixing parameters and efficient data taking, it is crucial to monitor and control the detector in real time. Environmental conditions also need to be monitored for stable operation of detectors as well as for safety reasons. In this paper, we report the design, hardware, operation, and performance of the slow control system.

  5. Slow saccades in bulbar-onset motor neurone disease.

    Science.gov (United States)

    Donaghy, Colette; Pinnock, Ralph; Abrahams, Sharon; Cardwell, Chris; Hardiman, Orla; Patterson, Victor; McGivern, R Canice; Gibson, J Mark

    2010-07-01

    Historical studies of eye movements in motor neurone disease (MND) have been conflicting although current findings suggest that eye movement abnormalities relate to frontal lobe impairment. Numerous case reports, however, describe slow saccades and supranuclear gaze palsies in patients with MND often associated with bulbar-onset disease. We performed a study of saccades and smooth pursuit in a large group of patients with MND to examine for any differences between bulbar-onset and spinal-onset patients. Forty-four patients (14 bulbar-onset and 30 spinal-onset patients) and 45 controls were recruited. Reflexive saccades, antisaccades and smooth pursuit were examined using infra-red oculography and all subjects then underwent neuropsychological evaluation. Reflexive saccades were found to be slower in bulbar-onset compared to spinal-onset patients and controls (p = 0.03, p = 0.05). Antisaccade latency (p = 0.01) and antisaccade type 1 errors (p = 0.03, p = 0.04) were increased in patients compared to controls. 'Proportion of time spent in smooth pursuit' and smooth pursuit 'velocity gain' were reduced in patients compared to controls (p = 0.000, p = 0.001). Antisaccade errors and velocity gain correlated with neuropsychological measures sensitive to lesions of the frontal lobes. This is the first study to highlight the presence of slow saccades in bulbar-onset MND. These findings suggest that slow saccades may be due to increased brainstem pathology in bulbar-onset disease that involves burst cell neurons. Furthermore these observations highlight the potential for overlap between bulbar-onset MND and progressive supranuclear palsy (PSP) as both can have a bulbar palsy and slowed saccades.

  6. Effects of stretching the scalene muscles on slow vital capacity

    OpenAIRE

    Lee, Juncheol; Hwang, Sehee; Han, Seungim; Han, Dongwook

    2016-01-01

    [Purpose] The purpose of this study was to examine whether stretching of the scalene muscles would improve slow vital capacity (SVC). [Subjects and Methods] The subjects of this study were 20 healthy female students to whom the study’s methods and purpose were explained and their agreement for participation was obtained. The SVC was measured using spirometry (Pony FX, COSMED Inc., Italy). The intervention used was stretching of the scalene muscles. Stretching was carried out for 15 min, 10 ti...

  7. Effects of cervical self-stretching on slow vital capacity

    OpenAIRE

    Han, Dongwook; Yoon, Nayoon; Jeong, Yeongran; Ha, Misook; Nam, Kunwoo

    2015-01-01

    [Purpose] This study investigated the effects of self-stretching of cervical muscles, because the accessory inspiratory muscle is considered to improve pulmonary function. [Subjects] The subjects were 30 healthy university students 19–21 years old who did not have any lung disease, respiratory dysfunction, cervical injury, or any problems upon cervical stretching. [Methods] Spirometry was used as a pulmonary function test to measure the slow vital capacity before and after stretching. The slo...

  8. Operational method for the space-energy slowing down problem

    Energy Technology Data Exchange (ETDEWEB)

    El Wakil, S.A.; Machali, H.M.; Madkour, M.A.; Saied, E.A.

    1988-01-01

    The direct operational method and Pade's approximation is used to transform the integro-differential form of the transport equation to differential form. The moment method and the similarity method are used to solve the space-energy problem in the slowing down region with energy-dependent cross section. The energy deposition factor is calculated in terms of the spatial-angular moments, without using the integral transform.

  9. Slow Neutron Velocity Spectrometer Transmission Studies Of Pu

    Science.gov (United States)

    Havens, W. W. Jr.; Melkonian, E.; Rainwater, L. J.; Levin, M.

    1951-05-28

    The slow neutron transmission of several samples of Pu has been investigated with the Columbia Neutron Velocity Spectrometer. Data are presented in two groups, those covering the energy region from 0 to 6 ev, and those covering the region above 6 ev. Below 6 ev the resolution was relatively good, and a detailed study of the cross section variation was made. Work above 6 ev consisted of merely locating levels and obtaining a rough idea of their strengths.

  10. Polarized 3 He Spin Filters for Slow Neutron Physics

    OpenAIRE

    Gentile, T. R.; W.C. Chen; Jones, G. L.; Babcock, E.; Walker, T. G.

    2005-01-01

    Polarized 3He spin filters are needed for a variety of experiments with slow neutrons. Their demonstrated utility for highly accurate determination of neutron polarization are critical to the next generation of betadecay correlation coefficient measurements. In addition, they are broadband devices that can polarize large area and high divergence neutron beams with little gamma-ray background, and allow for an additional spin-flip for systematic tests. These attributes are relevant to all neut...

  11. 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)

  12. Rotational evolution of slow-rotators sequence stars

    CERN Document Server

    Lanzafame, Alessandro C

    2015-01-01

    The observed mass-age-rotation relationship in open clusters shows the progressive development of a slow-rotators sequence at masses lower than 1.2 $M_{\\odot}$. After 0.6 Gyr, almost all stars have settled on this sequence. The observed clustering on this sequence suggests that it corresponds to some equilibrium or asymptotic condition that still lacks a complete theoretical interpretation, crucial to our understanding of the stellar angular momentum evolution. We couple a rotational evolution model that takes into account internal differential rotation with classical and new proposals for the wind braking law, and fit models to the data using a Monte Carlo Markov Chain method tailored to the case at hand. We explore the extent to which these models are able to reproduce the mass and time dependence of the stellar rotational evolution on the slow-rotators sequence. The description of the early evolution (0.1-0.6 Gyr) of the slow-rotators sequence requires taking into account the transfer of angular momentum f...

  13. Energy compensation of slow extracted beams with RF acceleration

    Science.gov (United States)

    Fujimoto, Tetsuya; Souda, Hikaru; Torikoshi, Masami; Kanai, Tatsuaki; Yamada, Satoru; Noda, Koji

    2016-03-01

    In a conventional carbon-ion radiotherapy facility, a carbon-ion beam is typically accelerated up to an optimum energy, slowly extracted from a synchrotron ring by a resonant slow extraction method, and ultimately delivered to a patient through a beam-delivery system. At Japan's Gunma University, a method employing slow-beam extraction along with beam-acceleration has been adopted. This method slightly alters the extracted-beam's energy owing to the acceleration component of the process, which subsequently results in a residual-range variation of approximately 2 mm in water-equivalent length. However, this range variation does not disturb a distal dose distribution with broad-beam methods such as the single beam-wobbling method. With the pencil-beam 3D scanning method, however, such a range variation disturbs a distal dose distribution because the variation is comparable to slice thickness. Therefore, for pencil-beam 3D scanning, an energy compensation method for a slow extracted beam is proposed in this paper. This method can compensate for the aforementioned energy variances by controlling net energy losses through a rotatable energy absorber set fixed between the synchrotron exit channel and the isocenter. Experimental results demonstrate that beam energies can be maintained constant, as originally hypothesized. Moreover, energy-absorber positions were found to be significantly enhanced by optimizing beam optics for reducing beam-size growth by implementation of the multiple-scattering effect option.

  14. Photorespiration in C4 grasses remains slow under drought conditions.

    Science.gov (United States)

    Carmo-Silva, Ana E; Powers, Stephen J; Keys, Alfred J; Arrabaça, Maria Celeste; Parry, Martin A J

    2008-07-01

    The CO(2)-concentrating mechanism present in C(4) plants decreases the oxygenase activity of ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) and, consequently, photorespiratory rates in air. Under drought conditions, the intercellular CO(2) concentration may decrease and cause photorespiration to increase. The C(4) grasses Paspalum dilatatum Poiret, Cynodon dactylon (L.) Pers. and Zoysia japonica Steudel were grown in soil and drought was imposed by ceasing to provide water. Net CO(2) assimilation (A) and stomatal conductance to water vapour decreased with leaf dehydration. Decreased carbon and increased oxygen isotope composition were also observed under drought. The response of A to CO(2) suggested that the compensation point was zero in all species irrespective of the extent of drought stress. A slight decrease of A as O(2) concentration increased above 10% provided evidence for slow photorespiratory gas exchanges. Analysis of amino acids contained in the leaves, particularly the decrease of glycine after 30 s in darkness, supported the presence of slow photorespiration rates, but these were slightly faster in Cynodon dactylon than in Paspalum dilatatum and Zoysia japonica. Although the contents of glycine and serine increased with dehydration and mechanistic modelling of C(4) photosynthesis suggested slightly increased photorespiration rates in proportion to photosynthesis, the results provide evidence that photorespiration remained slow under drought conditions.

  15. Multisteps Global Kinetic Analysis of MSW Slow Pyrolysis

    Directory of Open Access Journals (Sweden)

    Dwi Aries Himawanto

    2013-12-01

    Full Text Available 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 shieves then characterized in self manufactured macro balance. The thermogravimetry analyses were done to find the MSW slow pyrolysis characteristics. The 20 gram sample was placed in the furnace whose temperature is increased with 10 0C/min heating rate until reached 400 0 final temperature and held for 30 minutes before the sample is cooled into room temperature. One hundred ml/min nitrogen introduced from the bottom of furnace as a swept gas. The results of the research show that the global kinetic method could be used to predict the MSW single component activation energy but it should be modified to calculate the mixed sample activation energy . The predictive activation energy values which calculated based on weighed sum of single component have 18.5 % deviations if compared with experimental result.

  16. Biodegradation of MIB and geosmin with slow sand filters.

    Science.gov (United States)

    Hsieh, Shu-Ting; Lin, Tsair-Fuh; Wang, Gen-Shuh

    2010-01-01

    This study evaluated the biodegradation of MIB (2-methylisoborneol) and geosmin (trans-1,10-dimethyl-trans- 9-decalol) in simulated slow sand filtration (SSF) columns and in batch reactors. The results showed that both MIB and geosmin were biodegradable in the two systems. In batch experiments, the overall removals for MIB and geosmin were 50% and 78%, respectively, after 7 days of contact time. Volatilization loss plays an important role for geosmin in batch systems. Simulated SSF column studies also showed that more than 50% of geosmin and MIB were degraded by the microbial on the sand surface of a slow sand filter. With a filtration rate of 5 m/day, the simulated SSF degraded MIB from 48% to 69% and geosmin from 87% to 96%. The rapid biodegradation of MIB and geosmin in SSF column tests was attributed to the use of filter sands from the SSF unit in the Kinmen water treatment plant, where the microbial had been acclimated to both MIB and geosmin. The results also showed that more than 70% of the geosmin was removed in the top portion of the filter ( approximately 10 cm); while the removal of MIB occurred throughout the entire column depth. The results of this study demonstrated that slow flow through preacclimated sand was effective for control of MIB and geosmin in drinking water.

  17. Multifunctional slow-release organic-inorganic compound fertilizer.

    Science.gov (United States)

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

    2010-12-08

    Multifunctional slow-release organic-inorganic compound fertilizer (MSOF) has been investigated to improve fertilizer use efficiency and reduce environmental pollution derived from fertilizer overdosage. The special fertilizer is based on natural attapulgite (APT) clay used as a matrix, sodium alginate used as an inner coating and sodium alginate-g-poly(acrylic acid-co-acrylamide)/humic acid (SA-g-P(AA-co-AM)/HA) superabsorbent polymer used as an outer coating. The coated multielement compound fertilizer granules were produced in a pan granulator, and the diameter of the prills was in the range of 2.5-3.5 mm. The structural and chemical characteristics of the product, as well as its efficiency in slowing the nutrients release, were examined. In addition, a mathematical model for nutrient release from the fertilizer was applied to calculate the diffusion coefficient D of nutrients in MSOF. The degradation of the SA-g-P(AA-co-AM)/HA coating was assessed by examining the weight loss with incubation time in soil. It is demonstrated that the product prepared by a simple route with good slow-release property may be expected to have wide potential applications in modern agriculture and horticulture.

  18. Slow magnetosonic waves and fast flows in active region loops

    CERN Document Server

    Ofman, Leon; Davila, Joseph M

    2012-01-01

    Recent EUV spectroscopic observations indicate that slow magnetosonic waves are present in active region (AR) loops. Some of the spectral data were also interpreted as evidence of fast (~100-300 km/s) quasi-periodic flows. We have performed three-dimensional magnetohydrodynamic (3D MHD) modeling of a bipolar AR that contains impulsively generated waves and flows in coronal loops. The model AR is initiated with a dipole magnetic field and gravitationally stratified density, with an upflow driven steadily or periodically in localized regions at the footpoints of magnetic loops. The resulting flows along the magnetic field lines of the AR produce higher density loops compared to the surrounding plasma by injection of material into the flux-tubes and the establishment of siphon flow. We find that the impulsive onset of flows with subsonic speeds result in the excitation of damped slow magnetosonic waves that propagate along the loops and coupled nonlinearly driven fast mode waves. The phase speed of the slow magn...

  19. Slow Motion and Zoom in HD Digital Videos Using Fractals

    Directory of Open Access Journals (Sweden)

    Maurizio Murroni

    2009-01-01

    Full Text Available Slow motion replay and spatial zooming are special effects used in digital video rendering. At present, most techniques to perform digital spatial zoom and slow motion are based on interpolation for both enlarging the size of the original pictures and generating additional intermediate frames. Mainly, interpolation is done either by linear or cubic spline functions or by motion estimation/compensation which both can be applied pixel by pixel, or by partitioning frames into blocks. Purpose of this paper is to present an alternative technique combining fractals theory and wavelet decomposition to achieve spatial zoom and slow motion replay of HD digital color video sequences. Fast scene change detection, active scene detection, wavelet subband analysis, and color fractal coding based on Earth Mover's Distance (EMD measure are used to reduce computational load and to improve visual quality. Experiments show that the proposed scheme achieves better results in terms of overall visual quality compared to the state-of-the-art techniques.

  20. Standing Slow MHD Waves in Radiatively Cooling Coronal Loops

    Indian Academy of Sciences (India)

    K. S. Al-Ghafri

    2015-06-01

    The standing slow magneto-acoustic oscillations in cooling coronal loops are investigated. There are two damping mechanisms which are considered to generate the standing acoustic modes in coronal magnetic loops, namely, thermal conduction and radiation. The background temperature is assumed to change temporally due to optically thin radiation. In particular, the background plasma is assumed to be radiatively cooling. The effects of cooling on longitudinal slow MHD modes is analytically evaluated by choosing a simple form of radiative function, that ensures the temperature evolution of the background plasma due to radiation, coincides with the observed cooling profile of coronal loops. The assumption of low-beta plasma leads to neglecting the magnetic field perturbation and, eventually, reduces the MHD equations to a 1D system modelling longitudinal MHD oscillations in a cooling coronal loop. The cooling is assumed to occur on a characteristic time scale, much larger than the oscillation period that subsequently enables using the WKB theory to study the properties of standing wave. The governing equation describing the time-dependent amplitude of waves is obtained and solved analytically. The analytically derived solutions are numerically evaluated to give further insight into the evolution of the standing acoustic waves. We find that the plasma cooling gives rise to a decrease in the amplitude of oscillations. In spite of the reduction in damping rate caused by rising the cooling, the damping scenario of slow standing MHD waves strongly increases in hot coronal loops.