WorldWideScience

Sample records for c1 transfergenes deduced

  1. Fishing for biodiversity: Novel methanopterin-linked C1 transfergenes deduced from the Sargasso Sea metagenome

    Energy Technology Data Exchange (ETDEWEB)

    Kalyuzhnaya, Marina G.; Nercessian, Olivier; Lapidus, Alla; Chistoserdova, Ludmila

    2004-07-01

    The recently generated database of microbial genes from anoligotrophic environment populated by a calculated 1,800 of major phylotypes (the Sargasso Sea metagenome) presents a great source for expanding local databases of genes indicative of a specific function. In this paper we analyze the Sargasso Sea metagenome in terms of the presence of methanopterin-linked C1 transfer genes that are signature for methylotrophy. We conclude that more than 10 phylotypes possessing genes of interest are present in this environment, and a few of these are relatively abundant species. The sequences representative of the major phylotypes do not appear to belong to any known microbial group capable of methanopterin-linked C1 transfer. Instead, they separate from all known sequences on phylogenetic trees, pointing towards their affiliation with a novel microbial phylum. These data imply a broader distribution of methanopterin-linked functions in the microbial world than previously known.

  2. Fishing for biodiversity: Novel methanopterin-linked C1 transfer genes deduced from the Sargasso Sea metagenome

    OpenAIRE

    Kalyuzhnaya, Marina G.; Nercessian, Olivier; Lapidus, Alla; Chistoserdova, Ludmila

    2004-01-01

    The recently generated database of microbial genes from an oligotrophic environment populated by a calculated 1,800 of major phylotypes (the Sargasso Sea metagenome) presents a great source for expanding local databases of genes indicative of a specific function. In this paper we analyze the Sargasso Sea metagenome in terms of the presence of methanopterin-linked C1 transfer genes that are signature for methylotrophy. We conclude that more than 10 phylotypes possessing genes of interest ...

  3. Finite pure integer programming algorithms employing only hyperspherically deduced cuts

    Science.gov (United States)

    Young, R. D.

    1971-01-01

    Three algorithms are developed that may be based exclusively on hyperspherically deduced cuts. The algorithms only apply, therefore, to problems structured so that these cuts are valid. The algorithms are shown to be finite.

  4. Insufficiency of the quantum state for deducing observational probabilities

    International Nuclear Information System (INIS)

    It is usually assumed that the quantum state is sufficient for deducing all probabilities for a system. This may be true when there is a single observer, but it is not true in a universe large enough that there are many copies of an observer. Then the probability of an observation cannot be deduced simply from the quantum state (say as the expectation value of the projection operator for the observation, as in traditional quantum theory). One needs additional rules to get the probabilities. What these rules are is not logically deducible from the quantum state, so the quantum state itself is insufficient for deducing observational probabilities. This is the measure problem of cosmology.

  5. Microbial growth on C1 compounds: proceedings

    International Nuclear Information System (INIS)

    This book contains individual papers prepared for the 4th International Symposium on Microbial Growth on One Carbon Compounds. Individual reports were abstracted and indexed for EDB. Topics presented were in the areas of the physiology and biochemistry of autotraps, physiology and biochemistry of methylotrophs and methanotrops, physiology and biochemistry of methanogens, genetics of microbes that use C1 compounds, taxonomy and ecology of microbes tht grow on C1 compounds, applied aspects of microbes that grow on C1 compounds, and new directions in C1 metabolism. (DT)

  6. C1q and systemic lupus erythematosus.

    Science.gov (United States)

    Walport, M J; Davies, K A; Botto, M

    1998-08-01

    In this chapter we review the association between SLE and C1q. In the first part of the chapter we discuss the clinical associations of C1q deficiency, and tabulate the available information in the literature relating to C1q deficiency and autoimmune disease. Other clinical associations of C1q deficiency are then considered, and we mention briefly the association between other genetically determined complement deficiencies and lupus. In the review we explore the relationship between C1q consumption and lupus and we discuss the occurrence of low molecular weight (7S) C1q in lupus, which raises the possibility that increased C1q turnover in the disease may result in unbalanced chain synthesis of the molecule. Anti-C1q antibodies are also strongly associated with severe SLE affecting the kidney, and with hypocomplementaemic urticarial vasculitis, and these associations are also examined. We address the question of how C1q deficiency may cause SLE, discussing the possibility that this may be due to abnormalities of immune complex processing, which have been well characterised in a umber of different human models. There is clear evidence that immune complex processing is abnormal in patients with hypocomplementaemia, and this is compatible with the hypothesis that ineffective immune complex clearance could cause tissue injury, and this may in turn stimulate an autoantibody response. We have also considered the possibility that C1q-C1q receptor interactions are critical in the regulation of apoptosis, and we explore the hypothesis that dysregulation of apoptosis could explain important features in the development of autoimmune disease associated with C1q deficiency. An abnormally high rate of apoptosis, or defective clearance of apoptotic cells, could promote the accumulation of abnormal cellular products that might drive an autoimmune response. Anti-C1q antibodies have been described in a number of murine models of lupus, and these are also briefly discussed. We focus

  7. Autoantibodies against complement C1q specifically target C1q bound on early apoptotic cells.

    Science.gov (United States)

    Bigler, Cornelia; Schaller, Monica; Perahud, Iryna; Osthoff, Michael; Trendelenburg, Marten

    2009-09-01

    Autoantibodies against complement C1q (anti-C1q) are frequently found in patients with systemic lupus erythematosus (SLE). They strongly correlate with the occurrence of severe lupus nephritis, suggesting a pathogenic role in SLE. Because anti-C1q are known to recognize a neoepitope on bound C1q, but not on fluid-phase C1q, the aim of this study was to clarify the origin of anti-C1q by determining the mechanism that renders C1q antigenic. We investigated anti-C1q from serum and purified total IgG of patients with SLE and hypocomplementemic urticarial vasculitis as well as two monoclonal human anti-C1q Fab from a SLE patient generated by phage display. Binding characteristics, such as their ability to recognize C1q bound on different classes of Igs, on immune complexes, and on cells undergoing apoptosis, were analyzed. Interestingly, anti-C1q did not bind to C1q bound on Igs or immune complexes. Neither did we observe specific binding of anti-C1q to C1q bound on late apoptotic/necrotic cells when compared with binding in the absence of C1q. However, as shown by FACS analysis and confocal microscopy, anti-C1q specifically targeted C1q bound on early apoptotic cells. Anti-C1q were found to specifically target C1q bound on cells undergoing apoptosis. Our observations suggest that early apoptotic cells are a major target of the autoimmune response in SLE and provide a direct link between human SLE, apoptosis, and C1q. PMID:19648280

  8. Abundance of $C^1$-robust homoclinic tangencies

    CERN Document Server

    Bonatti, C

    2009-01-01

    A diffeomorphism $f$ has a $C^1$-robust homoclinic tangency if there is a $C^1$-neighbourhood $\\cU$ of $f$ such that every diffeomorphism in $g\\in \\cU$ has a hyperbolic set $\\La_g$, depending continuously on $g$, such that the stable and unstable manifolds of $\\La_g$ have some non-transverse intersection. For every manifold of dimension greater than or equal to three, we exhibit a local mechanism (blender-horseshoes) generating diffeomorphisms with $C^1$-robust homoclinic tangencies. Using blender-horseshoes, we prove that homoclinic classes of $C^1$-generic diffeomorphisms containing saddles with different indices and that do not admit dominated splittings (of appropriate dimensions) display $C^1$-robust homoclinic tangencies.

  9. Abundance of $C^1$-robust homoclinic tangencies

    OpenAIRE

    Bonatti, C.; Diaz, L. J.

    2009-01-01

    A diffeomorphism $f$ has a $C^1$-robust homoclinic tangency if there is a $C^1$-neighbourhood $\\cU$ of $f$ such that every diffeomorphism in $g\\in \\cU$ has a hyperbolic set $\\La_g$, depending continuously on $g$, such that the stable and unstable manifolds of $\\La_g$ have some non-transverse intersection. For every manifold of dimension greater than or equal to three, we exhibit a local mechanism (blender-horseshoes) generating diffeomorphisms with $C^1$-robust homoclinic tangencies. Using bl...

  10. Anti-C1q autoantibodies.

    Science.gov (United States)

    Kallenberg, Cees G M

    2008-09-01

    Autoantibodies to complement components are associated with various diseases. Anti-C1q antibodies are present in all patients with hypocomplementemic urticarial vasculitis, but also, with varying prevalence, in other conditions. In SLE, these antibodies are neither sensitive nor specific for this condition. They occur, however, more frequently in (proliferative) lupus nephritis, particularly during active disease. Furthermore, levels of anti-C1q rise, in many cases, prior to a relapse of lupus nephritis, suggesting a pathogenic role for the autoantibodies. Indeed, experimental studies strongly support a pathogenic role for anti-C1q in immune complex-mediated renal disease. In addition, anti-C1q may interfere with the clearance of apoptotic cells, so influencing induction and expression of autoimmunity. PMID:18606253

  11. Insufficiency of the Quantum State for Deducing Observational Probabilities

    OpenAIRE

    Page, Don N.

    2008-01-01

    It is usually assumed that the quantum state is sufficient for deducing all probabilities for a system. This may be true when there is a single observer, but it is not true in a universe large enough that there are many copies of an observer. Then the probability of an observation cannot be deduced simply from the quantum state (say as the expectation value of the projection operator for the observation, as in traditional quantum theory). One needs additional rules to get the probabilities. W...

  12. Deducing Reaction Mechanism: A Guide for Students, Researchers, and Instructors

    Science.gov (United States)

    Meek, Simon J.; Pitman, Catherine L.; Miller, Alexander J. M.

    2016-01-01

    An introductory guide to deducing the mechanism of chemical reactions is presented. Following a typical workflow for probing reaction mechanism, the guide introduces a wide range of kinetic and mechanistic tools. In addition to serving as a broad introduction to mechanistic analysis for students and researchers, the guide has also been used by…

  13. On orientifolds of c=1 orbifolds

    Energy Technology Data Exchange (ETDEWEB)

    Dijkstra, T.P.T. [NIKHEF, PO Box 41882, 1009 DB Amsterdam (Netherlands); Gato-Rivera, B. [NIKHEF, PO Box 41882, 1009 DB Amsterdam (Netherlands); Riccioni, F. [NIKHEF, PO Box 41882, 1009 DB Amsterdam (Netherlands)]. E-mail: f.riccioni@damtp.cam.ac.uk; Schellekens, A.N. [NIKHEF, PO Box 41882, 1009 DB Amsterdam (Netherlands)

    2004-10-25

    The aim of this paper is to study orientifolds of c=1 conformal field theories. A systematic analysis of the allowed orientifold projections for c=1 orbifold conformal field theories is given. We compare the Klein bottle amplitudes obtained at rational points with the orientifold projections that we claim to be consistent for any value of the orbifold radius. We show that the recently obtained Klein bottle amplitudes corresponding to exceptional modular invariants, describing bosonic string theories at fractional square radius, are also in agreement with those orientifold projections.

  14. On Orientifolds of c=1 Orbifolds

    CERN Document Server

    Dijkstra, T P T; Riccioni, F; Schellekens, Adrian Norbert

    2003-01-01

    The aim of this paper is to study orientifolds of c=1 conformal field theories. A systematic analysis of the allowed orientifold projections for c=1 orbifold conformal field theories is given. We compare the Klein bottle amplitudes obtained at rational points with the orientifold projections that we claim to be consistent for any value of the orbifold radius. We show that the recently obtained Klein bottle amplitudes corresponding to exceptional modular invariants, describing bosonic string theories at fractional square radius, are also in agreement with those orientifold projections.

  15. Anti-C1q autoantibodies

    NARCIS (Netherlands)

    Kallenberg, Cees G. M.

    2008-01-01

    Autoantibodies to complement components are associated with various diseases. Anti-C1q antibodies are present in all patients with hypocomplementemic urticarial vasculitis, but also, with varying prevalence, in other conditions. In SLE, these antibodies are neither sensitive nor specific for this co

  16. On the heat impulse method for deducing sap flow

    OpenAIRE

    Ron Gribben

    1999-01-01

    Speed of sap flow in plants and trees is of interest to botanists and environmentalists because of its connection with the rate of utilisation of nutrients in the soil. An established method uses the transport of heat where an impulsive heat source is introduced along a radial line by a probe in the trunk sapwood. The temperature is monitored, upstream and downstream, and, by solving the heat flow equation in the moving fluid, the sap velocity may be deduced indirectly under so...

  17. A new evolutionary theory deduced mathematically from entropy amplification

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    A new evolutionary theory which is able to unite the present evolutionary debates is deduced mathematically from the principle of entropy amplification.It suggests that the extensive evolution is driven by the amplification of entropy,or microscopic diversity,and the biological evolution is driven by the amplification of biodiversity.Forming high hierarchies is the most important way for the amplification and brings out spontaneously three kinds of selection.This theory has some positive cultural meanings.

  18. Photon strength function deduced from photon scattering and neutron capture

    Directory of Open Access Journals (Sweden)

    Matic A.

    2010-10-01

    Full Text Available The dipole strength function of 78Se and 196Pt are investigated by two different experimental methods, capture of cold neutrons in 77Se and 195Pt and photon scattering experiments on 78Se and 196Pt. Considering the different ways of excitation, the strength function deduced from the results are expected to agree. The report shows the status of the data analysis and presents first preliminary results.

  19. Cooperative Research in C1 Chemistry

    Energy Technology Data Exchange (ETDEWEB)

    Gerald P. Huffman

    2000-10-27

    C1 chemistry refers to the conversion of simple carbon-containing materials that contain one carbon atom per molecule into valuable products. The feedstocks for C1 chemistry include natural gas, carbon dioxide, carbon monoxide, methanol and synthesis gas (a mixture of carbon monoxide and hydrogen). Synthesis gas, or syngas, is produced primarily by the reaction of natural gas, which is principally methane, with steam. It can also be produced by gasification of coal, petroleum coke, or biomass. The availability of syngas from coal gasification is expected to increase significantly in the future because of increasing development of integrated gasification combined cycle (IGCC) power generation. Because of the abundance of remote natural gas, the advent of IGCC, and environmental advantages, C1 chemistry is expected to become a major area of interest for the transportation fuel and chemical industries in the relatively near future. The CFFLS will therefore perform a valuable national service by providing science and engineering graduates that are trained in this important area. Syngas is the source of most hydrogen. Approximately 10 trillion standard cubic feet (SCF) of hydrogen are manufactured annually in the world. Most of this hydrogen is currently used for the production of ammonia and in a variety of refining and chemical operations. However, utilization of hydrogen in fuel cells is expected to grow significantly in the next century. Syngas is also the feedstock for all methanol and Fischer-Tropsch plants. Currently, world consumption of methanol is over 25 million tons per year. There are many methanol plants in the U.S. and throughout the world. Methanol and oxygenated transportation fuel products play a significant role in the CFFLS C1 program. Currently, the only commercial Fischer-Tropsch plants are overseas, principally in South Africa (SASOL). However, new plants are being built or planned for a number of locations. One possible location for future F

  20. Precipitation processes as deduced by combining Doppler radar and disdrometer

    Science.gov (United States)

    Thomson, Alan Douglas

    Precipitation processes are investigated in stratiform and convective weather systems by combining Doppler radar and disdrometer measurements. Vertical scans are designed to measure the standard radar data fields and the power spectrum of the vertical Doppler velocities with high spatial and temporal resolution. A new method, based on iterative application of a disdrometer-determined Z-R relation, is developed to estimate vertical winds from the vertical scan data. Using this method, radar-based raindrop size spectra calculated near the surface in light stratiform rain compare well with simultaneous measurements from a collocated disdrometer. A full raindrop size spectrum profile is deduced for a specific steady state case. It is found that the spectrum does not vary with height, suggesting that the spectral shape is mainly controlled by the ice particles occurring above the 0oC level. Vertical scan data are also combined with volume scan data obtained by the Atmospheric Environment Service King City radar to examine the precipitation structure of a hail producing region within a severe squall line. The vertical scan shows a large variation in precipitation structure and also reveals important storm features which, in this case, are not detected by the conventional volume scans, such as a weak echo vault, a downdraught outflow, and streaks of very high downward velocity corresponding to separate hail trajectories. The power spectra were used to identify and locate hailstones, to deduce the growth of descending hailstones, and to qualitatively examine properties of raindrop size spectra. A conceptual model of hail formation is proposed by comparing the deduced storm structure and precipitation processes with the analyses of two somewhat similar storms documented in the literature.

  1. COOPERATIVE RESEARCH IN C1 CHEMISTRY

    Energy Technology Data Exchange (ETDEWEB)

    Gerald P. Huffman

    2001-04-30

    Faculty and students from five universities (Kentucky, West Virginia, Utah, Pittsburgh and Auburn) are collaborating on a basic research program to develop novel C1 chemistry processes for the production of clean, high quality transportation fuel. An Industrial Advisory Board (IAB) with members from Chevron, Eastman Chemical, Energy International, Teir Associates, and the Department of Defense has been formed to provide practical guidance to the program. The program has two principal objectives. (1) Develop technology for conversion of C1 source materials (natural gas, synthesis gas, carbon dioxide and monoxide, and methanol) into clean, high efficiency transportation fuel. (2) Develop novel processes for producing hydrogen from natural gas and other hydrocarbons. Some of the principal accomplishments of the program in its first two years are: (1) The addition of acetylenic compounds in Fischer-Tropsch synthesis is found to produce significant amounts of oxygenated products in FT diesel fuels. Such oxygenated products should decrease particulate matter (PM) emissions. (2) Nanoscale, binary, Fe-based catalysts supported on alumina have been shown to have significant activity for the decomposition of methane into pure hydrogen and potentially valuable multi-walled carbon nanotubes. (3) Catalytic synthesis processes have been developed for synthesis of diethyl carbonate, higher ethers, and higher alcohols from C1 source materials. Testing of the effect of adding these oxygenates to diesel fuel on PM emissions has begun using a well-equipped small diesel engine test facility. (4) Supercritical fluid (SCF) FT synthesis has been conducted under SCF hexane using both Fe and Co catalysts. There is a marked effect on the hydrocarbon product distribution, with a shift to higher carbon number products. These and other results are summarized.

  2. Temporal variability of TEC deduced from groundbased measurements

    International Nuclear Information System (INIS)

    This paper presents a study of the behaviour of the integrated total electron content (ITEC) deduced from electron density profiles of two Argentine stations: Tucuman (26.9 S; 294.6 E) and San Juan (31.5 S; 290.4 E). The ITEC values have been obtained by the technique proposed by Reinisch and Huang (2000). The database includes electron density profiles derived from ionograms recorded at 4 typical hours of the day (00.00, 06.00, 12.00 and 18.00 LT) during different seasonal and solar activity conditions. An analysis of the day to day variability of ITEC has also been done. (author)

  3. C1q protein binds to the apoptotic nucleolus and causes C1 protease degradation of nucleolar proteins.

    Science.gov (United States)

    Cai, Yitian; Teo, Boon Heng Dennis; Yeo, Joo Guan; Lu, Jinhua

    2015-09-11

    In infection, complement C1q recognizes pathogen-congregated antibodies and elicits complement activation. Among endogenous ligands, C1q binds to DNA and apoptotic cells, but whether C1q binds to nuclear DNA in apoptotic cells remains to be investigated. With UV irradiation-induced apoptosis, C1q initially bound to peripheral cellular regions in early apoptotic cells. By 6 h, binding concentrated in the nuclei to the nucleolus but not the chromatins. When nucleoli were isolated from non-apoptotic cells, C1q also bound to these structures. In vivo, C1q exists as the C1 complex (C1qC1r2C1s2), and C1q binding to ligands activates the C1r/C1s proteases. Incubation of nucleoli with C1 caused degradation of the nucleolar proteins nucleolin and nucleophosmin 1. This was inhibited by the C1 inhibitor. The nucleoli are abundant with autoantigens. C1q binding and C1r/C1s degradation of nucleolar antigens during cell apoptosis potentially reduces autoimmunity. These findings help us to understand why genetic C1q and C1r/C1s deficiencies cause systemic lupus erythematosus. PMID:26231209

  4. Hereditary Angioedema due to C1 Inhibitor Deficiency: C1-INH Replacement Therapy

    Directory of Open Access Journals (Sweden)

    Mauro Cancian

    2014-04-01

    Full Text Available Hereditary angioedema (HAE is a rare condition affecting about 1 in 50.000 individuals and caused by a mutation in the gene encoding the C1-esterase inhibitor (C1-INH, which is involved in the control of complement, clotting, fibrinolytic and kinin pathways. HAE is characterized by plasma outflow from blood vessels, leading to fluid collecting (edema in the deep tissue layers of the face, larynx, abdomen, and extremities. Three different types of HAE have been identified: in type I the mutation leads to the lack of production of C1-INH, in type II the mutation leads to the production of dysfunctional C1-INH, while type III is extremely rare and still not fully understood. Therapeutic approaches for HAE include on-demand treatments to stop angioedema attacks and prophylactic treatment to prevent attacks both by pre-procedural (short-term and routine (long-term prophylaxis. Aim of the present review is to present an overview of C1-INH replacement therapy with the plasma-derived concentrate of C1-INH Berinert® (CSL Behring GmbH in the treatment of type I and II HAE.http://dx.doi.org/10.7175/rhc.v5i2.913

  5. Advance of the perihelion of Mercury deduced from QFT

    Science.gov (United States)

    Chen, Shao-Guang

    I deduce the new gravitational formula from the variance in mass of QFT and GR (H05-0029-08, E15-0039 -08, E14-0032-08, D31-0054-10) in the partial differential: f (QFT) = f (GR) = delta∂ (m v)/delta∂ t = f _{P} + f _{C} , f _{P} = m delta∂ v / delta∂ t = - ( G m M /r (2) ) r / r, f _{C} = v delta∂ m / delta∂ t = - ( G m M / r (2) ) v / c (1), f (QFT) is the quasi-Casimir pressure of net virtual neutrinos nuν _{0} flux (after counteract contrary direction nuν _{0}). f (GR) is equivalent to Einstein’s equation, Eq. (1) is a new version of GR and can be solved exactly. Its core content is that the gravity produced by particles collide cannot linear addition, i.e., the nonlinearity of Einstein equation had been replaced by the nonlinearity caused by the variable mass in Eq.(1). Einstein equation can be inferred from Eq.(1) thereby from QFT, but QFT cannot be inferred from Eq.(1) or GR. f (QFT) is essential but f (GR) is phenomenological. Eq.(1) is obtained just by to absorb the essence of corpuscule collided gravitation origin ism proposed by Fatio in 1690 and 1920 Majorana’s experiment concept about gravitational shield effect again fuse with QFT. In my paper ‘QFT’S advance of the perihelion of Mercury, China Science &Technology Overview 125 88-90 (2011)’ QFT gravitational potential U = - G M /r is just the distribution density of net nuν _{0} flux, from SR we again get that: f (QFT) = f _{P} + f _{C}, f _{P} = - m ( delta∂ U / delta∂ r) r / r, f _{C} = - m ( delta∂U / delta∂ r) v / c (2), f _{ P} correspond the change rate of three-dimensional momentum p, f _{C} correspond the change rate of fourth dimensional momentum i m c which show directly as a dissipative force of mass change. According to Eq.(2) the circular motion is instability and elliptic motion is in the auto-stability state. In the fluctuation vacuum a particle with mass M neighbor another particle with mass m, the renormalization mass M and m will be less than that when

  6. Complete cDNA sequence of human complement C1s and close physical linkage of the homologous genes C1s and C1r

    International Nuclear Information System (INIS)

    Overlapping molecular clones encoding the complement subcomponent C1s were isolated from a human liver cDNA library. The nucleotide sequence reconstructed from these clones spans about 85% of the length of the liver C1s messenger RNAs, which occur in three distinct size classes around 3 kilobases in length. Comparisons with the sequence of C1r, the other enzymatic subcomponent of C1, reveal 40% amino acid identity and conservation of all the cysteine residues. Beside the serine protease domain, the following sequence motifs, previously described in C1r, were also found in C1s: (a) two repeats of the type found in the Ba fragment of complement factor B and in several other complement but also noncomplement proteins, (b) a cysteine-rich segment homologous to the repeats of epidermal growth factor precursor, and (c) a duplicated segment found only in C1r and C1s. Differences in each of these structural motifs provide significant clues for the interpretation of the functional divergence of these interacting serine protease zymogens. Hybridizations of C1r and C1s probes to restriction endonuclease fragments of genomic DNA demonstrate close physical linkage of the corresponding genes. The implications of this finding are discussed with respect to the evolution of C1r and C1s after their origin by tandem gene duplication and to the previously observed combined hereditary deficiencies of Clr and Cls

  7. C1-inhibitor (C1-INH) autoantibodies in hereditary angioedema. Strong correlation with the severity of disease in C1-INH concentrate naïve patients.

    Science.gov (United States)

    Varga, Lilian; Széplaki, Gábor; Visy, Beáta; Füst, George; Harmat, George; Miklós, Katalin; Németh, Julianna; Cervenak, László; Karádi, István; Farkas, Henriette

    2007-02-01

    The presence of autoantibodies to C1-inhibitor (C1-INH-Abs) is a hallmark of acquired C1-inhibitor deficiency. However, only scarce data are available on their prevalence in hereditary angioedema (HAE). In a prospective study performed between 2001 and 2004 in 95 patients with Type I or II HAE, serum samples were taken one to three times a year and clinical status of the patients was registered. Serum samples were tested for total activity of the classical pathway, C1q, C3, C4 and C1-inhibitor (C1-INH) concentration and activity levels, as well as the presence of IgG, IgA and IgM type anti-C1-inhibitor antibodies (C1-INH-Ab). Fifty-four healthy age and gender matched persons served as control. Significant differences between the patients and controls in the occurrence of elevated (2S.D. higher than mean of control) C1-INH-Abs titers was found only in the case of IgM type C1-INH-Abs. Elevated (>4.22AU/ml) IgM C1-INH-Abs levels were found in 31 and 4% of the patients and controls, respectively (p<0.001). Surprisingly, high titer IgM C1-INH-Abs were present with equal frequency in the 41 HAE patients ever treated with C1-INH concentrate and in the 54 C1-INH treatment naïve patients. In the latter group, strong positive correlation between the levels of the IgM C1-INH-Abs and the most severe disease (score 1) (p=0.0021) and the yearly attack rate (p=0.0173) were obtained. In addition, the levels of the IgM C1-INH-Abs exhibited strong negative correlation to the C1-inhibitor concentration and functional activity, total classical complement pathway activity, and a positive correlation to total IgM concentration. Taken together, these data indicate that IgM type C1-INH-Abs are present with highly elevated frequency in HAE patients irrespectively of the previous treatment with C1-INH concentrate. Most probable production of these autoantibodies is the consequence of the activation of complement and other plasma enzyme systems during HAE attacks. Determination of IgM C1

  8. Development of Deduced Protein Database Using Variable Bit Binary Encoding

    Directory of Open Access Journals (Sweden)

    B. Parvathavarthini

    2008-01-01

    Full Text Available A large amount of biological data is semi-structured and stored in any one the following file formats such as flat, XML and relational files. These databases must be integrated with the structured data available in relational or object-oriented databases. The sequence matching process is difficult in such file format, because string comparison takes more computation cost and time. To reduce the memory storage size of amino acid sequence in protein database, a novel probability-based variable bit length encoding technique has been introduced. The number of mapping of triplet CODON for every amino acid evaluates the probability value. Then, a binary tree has been constructed to assign unique bits of binary codes to each amino acid. This derived unique bit pattern of amino acid replaces the existing fixed byte representation. The proof of reduced protein database space has been discussed and it is found to be reduced between 42.86 to 87.17%. To validate our method, we have collected few amino acid sequences of major organisms like Sheep, Lambda phage and etc from NCBI and represented them using proposed method. The comparison shows that of minimum and maximum reduction in storage space are 43.30% and 72.86% respectively. In future the biological data can further be reduced by applying lossless compression on this deduced data.

  9. Deducing the three gauge interactions from the three Reidemeister moves

    International Nuclear Information System (INIS)

    We give one of the first known arguments for the origin of the three observed gauge groups. The argument is based on modelling nature at Planck scales as a collection of featureless strands that fluctuate in three dimensions. This approach models vacuum as untangled strands and particles as tangles of strands. Modelling vacuum as untangled strands implies the field equations of general relativity, when applying an argument from 1995 to the thermodynamics of strands. Modelling fermions as tangles of two or more strands allows to define wave functions as time-averages of strand crossings; using an argument from 1980, this allows to deduce the Dirac equation. When modelling fermions as tangled strands, gauge interactions appear naturally as deformation of tangle cores. The three possible types of observable core deformations are given by the three Reidemeister moves. They naturally lead to a U(1), a broken and parity-violating SU(2) and a SU(3) gauge group. The model is unique, is unmodifiable, is consistent with all known data, and makes numerous testable predictions, including the absence of other interactions, of grand unification and of higher dimensions. A method for calculating coupling constants seems to appear naturally.

  10. Interaction between complement subcomponent C1q and bacterial lipopolysaccharides.

    Science.gov (United States)

    Zohair, A; Chesne, S; Wade, R H; Colomb, M G

    1989-02-01

    The heptose-less mutant of Escherichia coli, D31m4, bound complement subcomponent C1q and its collagen-like fragments (C1qCLF) with Ka values of 1.4 x 10(8) and 2.0 x 10(8) M-1 respectively. This binding was suppressed by chemical modification of C1q and C1qCLF using diethyl pyrocarbonate (DEPC). To investigate the role of lipopolysaccharides (LPS) in this binding, biosynthetically labelled [14C]LPS were purified from E. coli D31m4 and incorporated into liposomes prepared from phosphatidylcholine (PC) and phosphatidylethanolamine (PE) [PC/PE/LPS, 2:2:1, by wt.]. Binding of C1q or its collagen-like fragments to the liposomes was estimated via a flotation test. These liposomes bound C1q and C1qCLF with Ka values of 8.0 x 10(7) and 2.0 x 10(7) M-1; this binding was totally inhibited after chemical modification of C1q and C1qCLF by DEPC. Liposomes containing LPS purified from the wild-strain E. coli K-12 S also bound C1q and C1qCLF, whereas direct binding of C1q or C1qCLF to the bacteria was negligible. Diamines at concentrations which dissociate C1 into C1q and (C1r, C1s)2, strongly inhibited the interaction of C1q or C1qCLF with LPS. Removal of 3-deoxy-D-manno-octulosonic acid (2-keto-3-deoxyoctonic acid; KDO) from E. coli D31m4 LPS decreases the binding of C1qCLF to the bacteria by 65%. When this purified and modified LPS was incorporated into liposomes, the C1qCLF binding was completely abolished. These results show: (i) the essential role of the collagen-like moiety and probably its histidine residues in the interaction between C1q and the mutant D31m4; (ii) the contribution of LPS, particularly the anionic charges of KDO, to this interaction. PMID:2649081

  11. Shadowing and Inverse Shadowing for C1 Endomorphisms

    Institute of Scientific and Technical Information of China (English)

    Yu Jun ZHU; Jin Lian ZHANG; Lian Fa HE

    2006-01-01

    In this paper, we consider the shadowing and the inverse shadowing properties for C1 endomorphisms. We show that near a hyperbolic set a C1 endomorphism has the shadowing property, and a hyperbolic endomorphism has the inverse shadowing property with respect to a class of continuous methods. Moreover, each of these shadowing properties is also "uniform" with respect to C1 perturbation.

  12. Revisiting the mechanism of the autoactivation of the complement protease C1r in the C1 complex: structure of the active catalytic region of C1r.

    Science.gov (United States)

    Kardos, József; Harmat, Veronika; Palló, Anna; Barabás, Orsolya; Szilágyi, Katalin; Gráf, László; Náray-Szabó, Gábor; Goto, Yuji; Závodszky, Péter; Gál, Péter

    2008-03-01

    C1r is a modular serine protease which is the autoactivating component of the C1 complex of the classical pathway of the complement system. We have determined the first crystal structure of the entire active catalytic region of human C1r. This fragment contains the C-terminal serine protease (SP) domain and the preceding two complement control protein (CCP) modules. The activated CCP1-CCP2-SP fragment makes up a dimer in a head-to-tail fashion similarly to the previously characterized zymogen. The present structure shows an increased number of stabilizing interactions. Moreover, in the crystal lattice there is an enzyme-product relationship between the C1r molecules of neighboring dimers. This enzyme-product complex exhibits the crucial S1-P1 salt bridge between Asp631 and Arg446 residues, and intermolecular interaction between the CCP2 module and the SP domain. Based on these novel structural information we propose a new split-and-reassembly model for the autoactivation of the C1r. This model is consistent with experimental results that have not been explained adequately by previous models. It allows autoactivation of C1r without large-scale, directed movement of C1q arms. The model is concordant with the stability of the C1 complex during activation of the next complement components. PMID:17996945

  13. PHOTOCONDUCTIVITY IN a-Si : H AND a-SixC1-x : H, CORRELATION WITH PHOTOLUMINESCENCE RESULTS

    OpenAIRE

    Caffier, D.; Le Contellec, M.; Richard, J.

    1981-01-01

    Photoconductivity and photoluminescence of a-Si : H and a-SixC1-x : H films prepared by glow discharge or R.F sputtering have been studied. For a-Si : H sputtered films, the photoconductivity is greatly increased with R.F power, substrate temperature and can be compared to values obtained for glow discharge films. The addition of a low carbon content (< 10 %) does not affect the photoconductivity but a higher content greatly decreases it. In conclusion, we deduced that the existence of a high...

  14. Anti-C1q antibodies in systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Orbai, A-M; Truedsson, L; Sturfelt, G;

    2015-01-01

    OBJECTIVE: Anti-C1q has been associated with systemic lupus erythematosus (SLE) and lupus nephritis in previous studies. We studied anti-C1q specificity for SLE (vs rheumatic disease controls) and the association with SLE manifestations in an international multicenter study. METHODS: Information...... serologies. Anti-C1q in combination with anti-dsDNA and low complement was the strongest serological association with renal involvement. These data support the usefulness of anti-C1q in SLE, especially in lupus nephritis....

  15. Hereditary angioedema with normal C1-INH (HAE type III).

    Science.gov (United States)

    Riedl, Marc A

    2013-01-01

    Hereditary angioedema (HAE) with normal C1 inhibitor (C1-INH), also known as HAE type III, is a familial condition only clinically recognized within the past three decades. Similar to HAE from C1-INH deficiency (HAE types I and II), affected individuals experience unpredictable angioedema episodes of the skin, gastrointestinal tract, and airway. Unique clinical features of HAE with normal C1-INH include the predominance of affected women, frequent exacerbation by estrogen, and a prominence of angioedema that involves the face and oropharynx. The underlying pathophysiology of HAE with normal C1-INH is poorly understood, but indirect evidence points to contact pathway dysregulation with bradykinin-mediated angioedema. Currently, evaluation is complicated by a lack of confirmatory laboratory testing such that clinical criteria must often be used to make the diagnosis of HAE with normal C1-INH. Factor XII mutations have been identified in only a minority of persons affected by HAE with normal C1-INH, limiting the utility of such analysis. To date, no controlled clinical studies have examined the efficacy of therapeutic agents for HAE with normal C1-INH, although published evidence supports frequent clinical benefit with medications shown effective in HAE due to C1-INH deficiency. PMID:24565612

  16. Acidic β-mannanase from Penicillium pinophilum C1: Cloning, characterization and assessment of its potential for animal feed application.

    Science.gov (United States)

    Cai, Hongying; Shi, Pengjun; Luo, Huiying; Bai, Yingguo; Huang, Huoqing; Yang, Peilong; Yao, Bin

    2011-12-01

    The β-mannanase gene, man5C1, was cloned from Penicillium pinophilum C1, a strain isolated from the acidic wastewater of a tin mine in Yunnan, China, and expressed in Pichia pastoris. The sequence analysis displayed the gene consists of a 1221-bp open reading frame encoding a protein of 406 amino acids (Man5C1). The deduced amino acid sequence of Man5C1 showed the highest homology of 57.8% (identity) with a characterized β-mannanase from Aspergillus aculeatus belonging to glycoside hydrolase family 5. The purified rMan5C1 had a high specific activity of 1035U mg(-1) towards locust bean gum (LBG) and showed highest activity at pH 4.0 and 70°C. rMan5C1 was adaptable to a wide range of acidity, retaining >60% of its maximum activity at pH 3.0-7.0. The enzyme was stable over a broad pH range (3.0 to 10.0) and exhibited good thermostability at 50°C. The K(m) and V(max) values were 5.6 and 4.8mgmL(-1), and 2785 and 1608μmolmin(-1)mg(-1), respectively, when LBG and konjac flour were used as substrates. The enzyme had strong resistance to most metal ions and proteases (pepsin and trypsin), and released 8.96mgg(-1) reducing sugars from LBG in the simulated gastric fluid. All these favorable properties make rMan5C1 a promising candidate for use in animal feed. PMID:22036533

  17. Anti-C1q in systemic lupus erythematosus.

    Science.gov (United States)

    Stojan, G; Petri, M

    2016-07-01

    C1q is the first component of the classical complement pathway. Both clinically validated in-house ELISA assays as well as commercial ELISA kits are used for detection of anti-C1q antibodies. Anti-C1q autoantibodies can be detected in a wide range of autoimmune diseases and are highly sensitive for hypocomplementemic uticarial vasculitis. In SLE, anti-C1q are strongly associated with proliferative lupus nephritis, and their absence carries a negative predictive value for development of lupus nephritis of close to 100%. Anti-C1q in combination with anti-dsDNA and low complement has the strongest serological association with renal involvement. The anti-C1q titers correlate with global disease activity scores in patients with renal involvement, and higher titers seem to precede renal flares. After the successful treatment of a renal flare, anti-C1q has the tendency to decrease or even become undetectable. The main obstacle to the inclusion of anti-C1q in the classification criteria and clinical management of SLE is the lack of standardized laboratory assays. PMID:27252264

  18. 26 CFR 31.3402(c)-1 - Wage bracket withholding.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 15 2010-04-01 2010-04-01 false Wage bracket withholding. 31.3402(c)-1 Section... SOURCE Collection of Income Tax at Source § 31.3402(c)-1 Wage bracket withholding. (a) In general. (1) The employer may elect to use the wage bracket method provided in section 3402(c) instead of...

  19. Isotope dependent predissociation in the C1Σ+, v=0 and v=1 states of

    International Nuclear Information System (INIS)

    Rotationally resolved spectral lines in the C-X(1, 0) band of carbon monoxide are investigated under high resolution using a coherent vacuum ultraviolet laser source, continuously tunable near 107 nm. Transition frequencies are determined by calibrating against a reference standard of iodine lines, recorded with saturation spectroscopy in the visible range, yielding an absolute accuracy of 0.003 cm-1 in the vacuum ultraviolet. Improved molecular constants for the excited state are derived and no effects of perturbation are found at the present level of accuracy. Line broadening measurements result in information on the excited state lifetime of the C1Σ+, v = 1 state for five natural isotopomers of carbon monoxide: τ(12C17O) = 280 ps, τ(12C18O) = 210 ps, τ(13C16O) = 295 ps, τ(13C17O) = 160 ps, and τ(13C18O) = 150 ps. Within the accuracy of the present measurements no effects of J-dependent lifetimes were observed, for neither of the isotopomers. In addition direct time domain measurements of the lifetime of the C1Σ+, v = 0 and v = 1 states of the main isotopomer are performed in a pump-probe experiment using a picosecond VUV-laser, yielding τ(12C16O) = 1780 ps for v = 0 and τ(12C16O) = 625 ps for v = 1. For C1Σ+, v = 0 in 12C16O and 13C16O the same lifetime is found; this lifetime matches experimental values of the oscillator strength and hence supports previous results showing pure radiative decay in this state; the error margins however do not exclude some low level of predissociation. The measurements indicate that the C1Σ+, v = 0 state of the 13C18O isotopomer is predissociated with an estimated yield of 17% (i.e. above the level of predissociation for 12C16O.) From the combined data predissociation yields upon excitation of the C1Σ+, v = 1 state are derived, lying in the range 0.84-0.91 for the five less abundant isotopomers; for the main 12C16O isotopomer a strongly deviating predissociation yield of 0.65 is deduced. (orig.)

  20. An Exact Bosonization Rule for c=1 Noncritical String Theory

    OpenAIRE

    Ishibashi, N.; A. Yamaguchi

    2007-01-01

    We construct a string field theory for c=1 noncritical strings using the loop variables as the string field. We show how one can express the nonrelativistic free fermions which describes the theory, in terms of these string fields.

  1. Unilateral extended suboccipital approach for a C1 dumbbell schwanoma

    Directory of Open Access Journals (Sweden)

    Gorgan R.M.

    2015-03-01

    Full Text Available Craniovertebral junction tumors represent a complex pathology carrying a high risk of injuring the vertebral artery and the lower cranial nerves. Dumbbell C1- C2 schannomas are very rare tumors in this location. We present a case of a 66 years old male accepted for left laterocervical localized pain, headache and vertigo, with a large C1 dumbbell schwannoma extending in lateral over the C1 arch and displacing the C3 segment of the vertebral artery superiorly and anteriorly. Complete removal of the tumor was achieved using a far lateral approach. The approach is discussed with focus on the vertebral artery anatomy as the approach should give enough space to gain control of the artery without creating instability. Safe removal of C1 nerve root schwanomas can be achieved even if they compress and displace the vertebral artery by entering a fibrous tissue plane between the tumor and the vertebral artery.

  2. 26 CFR 1.1402(c)-1 - Trade or business.

    Science.gov (United States)

    2010-04-01

    ...)-7, inclusive, the term “trade or business”, for the purpose of the tax on self-employment income... 26 Internal Revenue 12 2010-04-01 2010-04-01 false Trade or business. 1.1402(c)-1 Section 1.1402(c... (CONTINUED) INCOME TAXES Tax on Self-Employment Income § 1.1402(c)-1 Trade or business. In order for...

  3. Evaluation report on CCTF core-I reflood tests C1-6 (RUN 15), C1-9 (RUN 18), C1-11 (RUN 20) and C1-13 (RUN 22)

    International Nuclear Information System (INIS)

    The present report describes the effects of the Emergency Core Cooling (ECC) water injection rate on the reflooding phenomena observed in the Cylindrical Core Test Facility (CCTF). The evaluation is based on the data of Tests C1-5, C1-6, C1-9, C1-11 and C1-13 of the CCTF Core-I test series. In these tests, the injection rates of an accumulator system (Acc) and a low pressure coolant injection system (LPCI) and the injection duration of the Acc were parametrically varied from Test C1-5 (base case test). The higher ECC water injection rate caused the downcomer water head and core flooding rate to be higher resulting in the better core cooling. However, there was little effect of the LPCI injection rate on the core cooling once the downcomer water head reached the maximum level. Although the effects of the Acc injection rate and duration on the primary system thermo-hydrodynamic behavior and the core cooling behavior were dominant in an early period of the transient, they also significantly influenced the core cooling behavior through the whole transient. The similar trends of the effect of Acc injection rate on the core cooling behavior were observed in the CCTF and the FLECHT-SET Phase A experiments. (author)

  4. Safety and Usage of C1-Inhibitor in Hereditary Angioedema

    DEFF Research Database (Denmark)

    Riedl, Marc A; Bygum, Anette; Lumry, William;

    2016-01-01

    ) and 16.6 IU/kg (prophylaxis). Approximately 95% of infusions were administered outside of a health care setting. No adverse events (AEs) were reported in retrospective data. Among prospective data (n = 296 subjects; 9148 infusions), 252 AEs were reported in 85 (28.7%) subjects (rate of 0.03 events....../infusion); 9 events were considered related to pnfC1-INH. Two thromboembolic events were reported in subjects with thrombotic risk factors. No patient was noted to have undergone viral testing for suspected blood-borne infection during registry participation. CONCLUSIONS: The findings from this large......, international patient registry documented widespread implementation of pnfC1-INH self-administration outside of a health care setting consistent with current HAE guidelines. These real-world data revealed pnfC1-INH usage for a variety of reasons in patients with HAE and showed a high level of safety regardless...

  5. Novel C-1 Substituted Cocaine Analogs Unlike Cocaine or Benztropine

    OpenAIRE

    Reith, Maarten E.A.; Ali, Solav; Hashim, Audrey; Sheikh, Imran S.; Theddu, Naresh; Gaddiraju, Narendra V.; Mehrotra, Suneet; Schmitt, Kyle C.; Murray, Thomas F.; Sershen, Henry; Unterwald, Ellen M.; Davis, Franklin A.

    2012-01-01

    Despite a wealth of information on cocaine-like compounds, there is no information on cocaine analogs with substitutions at C-1. Here, we report on (R)-(−)-cocaine analogs with various C-1 substituents: methyl (2), ethyl (3), n-propyl (4), n-pentyl (5), and phenyl (6). Analog 2 was equipotent to cocaine as an inhibitor of the dopamine transporter (DAT), whereas 3 and 6 were 3- and 10-fold more potent, respectively. None of the analogs, however, stimulated mouse locomotor activity, in contrast...

  6. Lax matrix solution of c=1 Conformal Field Theory

    CERN Document Server

    Eynard, Bertrand

    2013-01-01

    To a correlation function in a two-dimensional conformal field theory with the central charge c=1, we associate a matrix differential equation \\Psi'=L\\Psi, where the Lax matrix L is a matrix square root of the energy-momentum tensor. Then local conformal symmetry translates into isomonodromy of the differential equation. This provides a justification for the recently observed relation between four-point conformal blocks and solutions of the Painleve VI equation. This also provides a direct way to compute the three-point function of Runkel-Watts theory - the common c->1 limit of Minimal Models and Liouville theory.

  7. Topological cigar and the c=1 string: Open and closed

    International Nuclear Information System (INIS)

    We clarify some aspects of the map between the c=1 string theory at self-dual radius and the topologically twisted cigar at level one. We map the ZZ and FZZT D-branes in the c=1 string theory at self dual radius to the localized and extended branes in the topological theory on the cigar. We show that the open string spectrum on the branes in the two theories are in correspondence with each other, and their two point correlators are equal. We also find a representation of an extended N = 2 algebra on the worldsheet which incorporates higher spin currents in terms of asymptotic variables on the cigar. (author)

  8. Method of estimating horizontal vectors of ionospheric electric field deduced from HF Doppler data

    International Nuclear Information System (INIS)

    An HF Doppler method for estimating the time variations of the horizontal electric field in the ionosphere is presented which takes into account, for long-lasting variations in the electric field, the effect of electron decay due to attachment and/or recombination processes. The method is applied to an isolated substorm event, using equivalent ionospheric current systems deduced from worldwide magnetometer data in the estimations. The present results are found to agree with data deduced from current systems and high latitude electrojet activity. 18 references

  9. Method of estimating horizontal vectors of ionospheric electric field deduced from HF Doppler data

    Energy Technology Data Exchange (ETDEWEB)

    Tsutsui, M.; Ogawa, T.; Kamide, Y.; Kroehl, H.W.; Hausman, B.A.

    1988-04-01

    An HF Doppler method for estimating the time variations of the horizontal electric field in the ionosphere is presented which takes into account, for long-lasting variations in the electric field, the effect of electron decay due to attachment and/or recombination processes. The method is applied to an isolated substorm event, using equivalent ionospheric current systems deduced from worldwide magnetometer data in the estimations. The present results are found to agree with data deduced from current systems and high latitude electrojet activity. 18 references.

  10. 26 CFR 1.514(c)-1 - Acquisition indebtedness.

    Science.gov (United States)

    2010-04-01

    ... (CONTINUED) INCOME TAXES (CONTINUED) Taxation of Business Income of Certain Exempt Organizations § 1.514(c)-1... where State law provides that a tax lien attaches to property prior to the time when such lien becomes... and payable and the organization has had an opportunity to pay such lien in accordance with State...

  11. Isometric C1-immersions for pairs of Riemannian metrics

    International Nuclear Information System (INIS)

    Let h1, h2 be two Euclidean metrics on Rq, and let V be a C∞-manifold endowed with two Riemannian metrics g1 and g2. We study the existence of C1-immersions f:(V,g1,g2)→(Rq,h1,h2) such that f*(hi)=gi for i=1,2. (author)

  12. Pediatric hereditary angioedema due to C1-inhibitor deficiency

    Directory of Open Access Journals (Sweden)

    Farkas Henriette

    2010-07-01

    Full Text Available Abstract Hereditary angioedema (HAE resulting from the deficiency of the C1 inhibitor (C1-INH is a rare, life-threatening disorder. It is characterized by attacks of angioedema involving the skin and/or the mucosa of the upper airways, as well as the intestinal mucosa. In approximately 50 per cent of cases, clinical manifestations may appear during childhood. The complex management of HAE in pediatric patients is in many respects different from the management of adults. Establishing the diagnosis early, preferably before the onset of clinical symptoms, is essential in cases with a positive family history. Complement studies usually afford accurate diagnosis, whereas molecular genetics tests may prove helpful in uncertain cases. Appropriate therapy, supported by counselling, suitable modification of lifestyle, and avoidance of triggering factors (which primarily include mechanical trauma, mental stress and airway infections in children may spare the patient unnecessary surgery and may prevent mortality. Prompt control of edematous attacks, short-term prophylaxis and intermittent therapy are recommended as the primary means for the management of pediatric cases. Medicinal products currently used for the treatment of children with hereditary angioedema include antifibrinolytics, attenuated androgens, and C1-INH replacement therapy. Current guidelines favour antifibrinolytics for long-term prophylaxis because of their favorable safety profile but efficacy may be lacking. Attenuated androgens administered in the lowest effective dose are another option. C1-INH replacement therapy is also an effective and safe agent for children. Regular monitoring and follow-up of patients are necessary.

  13. CONSISTENT USE OF THE KALMAN FILTER IN CHEMICAL TRANSPORT MODELS (CTMS) FOR DEDUCING EMISSIONS

    Science.gov (United States)

    Past research has shown that emissions can be deduced using observed concentrations of a chemical, a Chemical Transport Model (CTM), and the Kalman filter in an inverse modeling application. An expression was derived for the relationship between the "observable" (i.e., the con...

  14. New Route to Deducing Integration Formulas by Virtue of the IWOP Technique*

    Institute of Scientific and Technical Information of China (English)

    FAN Hong-Yi; LI Hong-Qi; XU Xing-Lei

    2011-01-01

    We point out a new route to deducing integration formulas, i.e., using the technique of integration within an ordered product (IWOP) of operators we derive some new integration formulas, which seems concise. As a by-product,some new operator identities also appear.

  15. A Deduced Feynman Rule for Calculating Retarded and Advanced Green function in Closed Time Path Formalism

    OpenAIRE

    Xiao, Jun; Wang, Enke(Key Laboratory of Quark and Lepton Physics (MOE) and Institute of Particle Physics, Central China Normal University, 430079, Wuhan, China)

    2002-01-01

    Based on the closed time path formalism, a new Feynman rule for directly calculating the retarded and advanced Green functions is deduced. This Feynman rule is used to calculate the two-point self-energy and three-point vertex correction in $\\phi^3$ theory. The generalized fluctuation-dissipation theorem for three-point nonlinear response function is verified.

  16. Complete amino acid sequence of human intestinal aminopeptidase N as deduced from cloned cDNA

    DEFF Research Database (Denmark)

    Cowell, G M; Kønigshøfer, E; Danielsen, E M;

    1988-01-01

    The complete primary structure (967 amino acids) of an intestinal human aminopeptidase N (EC 3.4.11.2) was deduced from the sequence of a cDNA clone. Aminopeptidase N is anchored to the microvillar membrane via an uncleaved signal for membrane insertion. A domain constituting amino acid 250...

  17. Quantum and classical aspects of deformed c = 1 strings

    International Nuclear Information System (INIS)

    The quantum and classical aspects of a deformed c=1 matrix model proposed by Jevicki and Yoneya are studied. String equations are formulated in the framework of the Toda lattice hierarchy. The Whittaker functions now play the role of generalized Airy functions in c<1 strings. This matrix model has two distinct parameters. Identification of the string coupling constant is thereby not unique, and leads to several different perturbative interpretations of this model as a string theory. Two such possible interpretations are examined. In both cases, the classical limit of the string equations, which turns out to give a formal solution of Polchinski's scattering equations, shows that the classical scattering amplitudes of massless tachyons are insensitive to deformations of the parameters in the matrix model. (author)

  18. On consistent boundary conditions for c = 1 string theory

    CERN Document Server

    O'Loughlin, M H

    1995-01-01

    We introduce a new parametrisation for the Fermi sea of the c = 1 matrix model. This leads to a simple derivation of the scattering matrix, and a calculation of boundary corrections in the corresponding 1+1--dimensional string theory. The new parametrisation involves relativistic chiral fields, rather than the non-relativistic fields of the usual formulations. The calculation of the boundary corrections, following recent work of Polchinski, allows us to place restrictions on the boundary conditions in the matrix model. We provide a consistent set of boundary conditions, but believe that they need to be supplemented by some more subtle relationship between the space-time and matrix model. Inspired by these boundary conditions, some thoughts on the black hole in c=1 string theory are presented.

  19. $C^{1,\\alpha}$ estimates for the parallel refractor

    CERN Document Server

    Abedin, Farhan; Tralli, Giulio

    2016-01-01

    We consider the parallel refractor problem when the planar radiating source lies in a medium having higher refractive index than the medium in which the target is located. We prove local $C^{1,\\alpha}$ estimates for parallel refractors under suitable geometric assumptions on the source and target, and under local regularity hypotheses on the target set. We also discuss existence of refractors under energy conservation assumptions.

  20. Intestinal and Hepatic Niemann-Pick C1-Like 1

    OpenAIRE

    Sung-Woo Park

    2013-01-01

    Polytopic transmembrane protein, Niemann-Pick C1-Like 1 (NPC1L1) is localized at the apical membrane of enterocytes and the canalicular membrane of hepatocytes. It mediates intestinal cholesterol absorption and prevents extensive loss of cholesterol by transporting biliary cholesterol into hepatocytes. NPC1L1 is a molecular target of ezetimibe, an agent for hypercholesterolemia. Recently, NPC1L1 inhibition has been shown to prevent metabolic disorders such as fatty liver disease, obesity, dia...

  1. On Consistent Boundary Conditions for c=1 String Theory

    OpenAIRE

    O'Loughlin, Martin

    1995-01-01

    We introduce a new parametrisation for the Fermi sea of the $c = 1$ matrix model. This leads to a simple derivation of the scattering matrix, and a calculation of boundary corrections in the corresponding $1+1$--dimensional string theory. The new parametrisation involves relativistic chiral fields, rather than the non-relativistic fields of the usual formulations. The calculation of the boundary corrections, following recent work of Polchinski, allows us to place restrictions on the boundary ...

  2. Double-scaled field theory at c=1

    International Nuclear Information System (INIS)

    We investigate the double-scaled free fermion theory of the c=1 matrix model. We compute correlation functions of the eigenvalue density field and compare with the predictions of a relativistic boson theory. The c=1 theory behaves as a relativistic theory at long distances, but has softer behavior at short distances. The soft-distance behavior is closely related to the breakdown of the topological expansion at high energies. We also compute macroscopic loop amplitudes at c=1, finding an integral representation for n-loop amplitudes to all orders of perturbation theory. We evaluate the integrals explicitly for two, three, and four macroscopic loops. The small loop length asymptotic expansion then gives correlation functions of local operators in the theory. The two-macroscopic-loop formula gives information on the spectrum and wave functions in the theory. The three- and four-loop amplitudes give scattering amplitudes for tachyon operators to all orders of perturbation theory. Again, the topological expansion breaks down at high energies. We compare our amplitudes with predictions from the Liouville theory. (orig.)

  3. Amplitude analyses of the decays chi_c1 -> eta pi+ pi- and chi_c1 -> eta' pi+ pi-

    CERN Document Server

    Adams, G S; Ecklund, K M; Insler, J; Muramatsu, H; Park, C S; Pearson, L J; Thorndike, E H; Ricciardi, S; Thomas, C; Artuso, M; Blusk, S; Mountain, R; Skwarnicki, T; Stone, S; Zhang, L M; Bonvicini, G; Cinabro, D; Lincoln, A; Smith, M J; Zhou, P; Zhu, J; Naik, P; Rademacker, J; Asner, D M; Edwards, K W; Randrianarivony, K; Tatishvili, G; Briere, R A; Vogel, H; Onyisi, P U E; Rosner, J L; Alexander, J P; Cassel, D G; Das, S; Ehrlich, R; Gibbons, L; Gray, S W; Hartill, D L; Heltsley, B K; Kreinick, D L; Kuznetsov, V E; Patterson, J R; Peterson, D; Riley, D; Ryd, A; Sadoff, A J; Shi, X; Sun, W M; Yelton, J; Rubin, P; Lowrey, N; Mehrabyan, S; Selen, M; Wiss, J; Libby, J; Kornicer, M; Mitchell, R E; Shepherd, M R; Szczepaniak, A; Besson, D; Pedlar, T K; Cronin-Hennessy, D; Hietala, J; Dobbs, S; Metreveli, Z; Seth, K K; Tomaradze, A; Xiao, T; Martin, L; Powell, A; Wilkinson, G; Ge, J Y; Miller, D H; Shipsey, I P J; Xin, B

    2011-01-01

    Using a data sample of 2.59 x 10^7 psi(2S) decays obtained with the CLEO-c detector, we perform amplitude analyses of the complementary decay chains chi_c1 -> eta pi+ pi- and chi_c1 -> eta' pi+ pi-. We find evidence for a P-wave eta' pi scattering amplitude, which, if interpreted as a resonance, would have exotic J^PC = 1^-+ and parameters consistent with the pi_1(1600) state reported in other production mechanisms. We also make the first observation of the decay a_0(980) -> eta' pi and measure the ratio of branching fractions B(a_0(980) -> eta' pi)/B(a_0(980) -> eta pi) = 0.064 +- 0.014 +- 0.014. The pi pi spectrum produced with a recoiling eta is compared to that with eta' recoil.

  4. Reduction of CO2 to C1 products and fuel

    Science.gov (United States)

    Mill, T.; Ross, D.

    2002-01-01

    Photochemical semiconductor processes readily reduced CO2 to a broad range of C1 products. However the intrinsic and solar efficiencies for the processes were low. Improved quantum efficiencies could be realized utilizing quantum-sized particles, but at the expense of using less of the visible solar spectrum. Conversely, semiconductors with small bandgaps used more of the visible solar spectrum at the expense of quantum efficiency. Thermal reduction of CO2 with Fe(II) was thermodynamically favored for forming many kinds of organic compounds and occurred readily with olivine and other Fe(II) minerals above 200??C to form higher alkanes and alkenes. No added hydrogen was required.

  5. Linearization of class C1 for contractions on Banach spaces

    Science.gov (United States)

    Rodrigues, Hildebrando M.; Solà-Morales, J.

    In this work we prove a C1-linearization result for contraction diffeomorphisms, near a fixed point, valid in infinite-dimensional Banach spaces. As an intermediate step, we prove a specific result of existence of invariant manifolds, which can be interesting by itself and that was needed on the proof of our main theorem. Our results essentially generalize some classical results by P. Hartman in finite dimensions, and a result of Mora-Sola-Morales in the infinite-dimensional case. It is shown that the result can be applied to some abstract systems of semilinear damped wave equations.

  6. Topological B-model and ${\\hat c}=1$ String Theory

    CERN Document Server

    Hyun, S; Park, J D; Yi, S H; Hyun, Seungjoon; Oh, Kyungho; Park, Jong-Dae; Yi, Sang-Heon

    2005-01-01

    We study the topological B-model on a deformed $\\Z_2$ orbifolded conifold by investigating variation of complex structures via quantum Kodaira-Spencer theories. The fermionic/brane formulation together with systematic utilization of symmetries of the geometry gives rise to a free fermion realization of the amplitudes. We derive Ward identities which solve the perturbed free energy exactly. We also obtain the corresponding Kontsevich-like matrix model. All these confirm the recent conjecture on the connection of the theory with ${\\hat c}=1$ type 0A string theory compactified at the radius $R=\\sqrt{\\alpha'/2}$.

  7. Fission fragment mass yield deduced from density distribution in the pre-scission configuration

    OpenAIRE

    Warda, M.; Zdeb, A.

    2015-01-01

    Static self-consistent methods usually allow to determine the most probable fission fragments mass asymmetry. We have applied random neck rupture mechanism to the nuclei in the configuration at the end of fission paths. Fission fragment mass distributions have been deduced from the pre-scission nuclear density distribution obtained from the self-consistent calculations. Potential energy surfaces as well as nuclear shapes have been calculated in the fully microscopic theory, namely the constra...

  8. On the influence of neutral turbulence on ambipolar diffusivities deduced from meteor trail expansion

    Directory of Open Access Journals (Sweden)

    C. M. Hall

    Full Text Available By measuring fading times of radar echoes from underdense meteor trails, it is possible to deduce the ambipolar diffusivities of the ions responsible for these radar echoes. It could be anticipated that these diffusivities increase monotonically with height akin to neutral viscosity. In practice, this is not always the case. Here, we investigate the capability of neutral turbulence to affect the meteor trail diffusion rate.

    Key words. Meteorology and atmospheric dynamics (middle atmosphere dynamics; turbulence

  9. MAGNETIC ANOMALY LINEATION AND FRACTURE ZONE IN ENDERBY BASIN DEDUCED FROM GEOMAGNETIC ANOMALY FIELD VECTOR

    OpenAIRE

    ノギ, ヨシフミ; セアマ, ノブカズ; イセザキ, ノブヒロ; フクダ, ヨウイチ; Yoshifumi, NOGI; Nobukazu, SEAMA; Nobuhiro, ISEZAKI; Yoichi, FUKUDA

    1995-01-01

    The formation of magnetic anomaly lineations and fracture zones in Enderby Basin (10°E-80°E), Southern Indian Ocean, are vital to understanding process of the Gondwana breakup. Vector anomalies of the geomagnetic field were obtained during the 30th, 31st, 32nd, and 33rd Japanese Antarctic Research Expeditions. The strikes of the magnetic anomaly lineations and fracture zones were deduced from vector geomagnetic anomaly field data as well as seasurface and satellite gravity anomalies. We surmi...

  10. The DEDUCE Guided Query tool: providing simplified access to clinical data for research and quality improvement.

    Science.gov (United States)

    Horvath, Monica M; Winfield, Stephanie; Evans, Steve; Slopek, Steve; Shang, Howard; Ferranti, Jeffrey

    2011-04-01

    In many healthcare organizations, comparative effectiveness research and quality improvement (QI) investigations are hampered by a lack of access to data created as a byproduct of patient care. Data collection often hinges upon either manual chart review or ad hoc requests to technical experts who support legacy clinical systems. In order to facilitate this needed capacity for data exploration at our institution (Duke University Health System), we have designed and deployed a robust Web application for cohort identification and data extraction--the Duke Enterprise Data Unified Content Explorer (DEDUCE). DEDUCE is envisioned as a simple, web-based environment that allows investigators access to administrative, financial, and clinical information generated during patient care. By using business intelligence tools to create a view into Duke Medicine's enterprise data warehouse, DEDUCE provides a Guided Query functionality using a wizard-like interface that lets users filter through millions of clinical records, explore aggregate reports, and, export extracts. Researchers and QI specialists can obtain detailed patient- and observation-level extracts without needing to understand structured query language or the underlying database model. Developers designing such tools must devote sufficient training and develop application safeguards to ensure that patient-centered clinical researchers understand when observation-level extracts should be used. This may mitigate the risk of data being misunderstood and consequently used in an improper fashion. PMID:21130181

  11. C1 inhibitor deficiency: 2014 United Kingdom consensus document.

    Science.gov (United States)

    Longhurst, H J; Tarzi, M D; Ashworth, F; Bethune, C; Cale, C; Dempster, J; Gompels, M; Jolles, S; Seneviratne, S; Symons, C; Price, A; Edgar, D

    2015-06-01

    C1 inhibitor deficiency is a rare disorder manifesting with recurrent attacks of disabling and potentially life-threatening angioedema. Here we present an updated 2014 United Kingdom consensus document for the management of C1 inhibitor-deficient patients, representing a joint venture between the United Kingdom Primary Immunodeficiency Network and Hereditary Angioedema UK. To develop the consensus, we assembled a multi-disciplinary steering group of clinicians, nurses and a patient representative. This steering group first met in 2012, developing a total of 48 recommendations across 11 themes. The statements were distributed to relevant clinicians and a representative group of patients to be scored for agreement on a Likert scale. All 48 statements achieved a high degree of consensus, indicating strong alignment of opinion. The recommendations have evolved significantly since the 2005 document, with particularly notable developments including an improved evidence base to guide dosing and indications for acute treatment, greater emphasis on home therapy for acute attacks and a strong focus on service organization. PMID:25605519

  12. Prophylaxis in hereditary angioedema (HAE) with C1 inhibitor deficiency.

    Science.gov (United States)

    Greve, Jens; Strassen, Ulrich; Gorczyza, Marina; Dominas, Nina; Frahm, Uta-Marie; Mühlberg, Heike; Wiednig, Michaela; Zampeli, Vasiliki; Magerl, Markus

    2016-03-01

    Hereditary angioedema (HAE) is a rare congenital disorder characterized by recurrent episodes of subcutaneous or submucosal edema. Laryngeal manifestations can be life-threatening. In the majority of cases, the disease can be adequately treated with an on-demand approach - in some cases, however, short- or long-term prophylaxis is indicated. Attenuated androgens used to be the drugs of choice, but they are associated with considerable side effects and no longer commercially available in the German-speaking countries of the EU. They are currently being replaced by more effective and more tolerable agents such C1-inhibitors, the kallikrein inhibitor ecallantide, and the B2 receptor antagonist icatibant, which have recently obtained market authorization. These new drugs have had a major impact, especially on the indications and procedures for long-term prophylaxis. According to the most recent international consensus papers and our own experience, self-administered C1-inhibitors are now the first option for long-term prophylactic therapy. The decision for prophylaxis should no longer be based on single parameters such as the frequency of attacks but on adequate overall disease control including quality of life. More drugs are currently being developed, which may lead to further changes in the treatment algorithms of HAE. PMID:26972189

  13. Land validation for GCOM-C1/SGLI using UAV

    Science.gov (United States)

    Honda, Yhosiaki; Kajiwara, Koji; Sharma, Ram; Ono, Akiko; Imaoka, Keiji; Murakami, Hiroshi; Hori, Masahiro; Ono, Yusaku; Rostand, Dim

    2012-09-01

    Japan Aerospace Exploration Agency (JAXA) is going to launch new Earth observation satellite GCOM-C1 in near future. The core sensor of GCOM-C1, Second Generation Global Imager (SGLI) has a set of along track slant viewing Visible and Near Infrared Radiometer (VNR). These multi-angular views aim to detect the structural information from vegetation canopy, especially forest canopy, for estimating productivity of the vegetation. SGLI Land science team has been developing the algorithm for above ground biomass, canopy roughness index, shadow index, etc. In this paper, we introduce the ground observation method developed by using Unmanned Aerial Vehicle (UAV) in order to contribute the algorithm development and its validation. Mainly, multi-angular spectral observation method and simple BRF model have been developed for estimating slant view response of forest canopy. The BRF model developed by using multi-angular measurement has been able to obtain structural information from vegetation canopy. In addition, we have conducted some observation campaigns on typical forest in Japan in collaboration with other science team experienced with vegetation phenology and carbon flux measurement. Primary results of these observations are also be demonstrated.

  14. Interaction of HmC1q with leech microglial cells: involvement of C1qBP-related molecule in the induction of cell chemotaxis

    Directory of Open Access Journals (Sweden)

    Tahtouh Muriel

    2012-02-01

    Full Text Available Abstract Background In invertebrates, the medicinal leech is considered to be an interesting and appropriate model to study neuroimmune mechanisms. Indeed, this non-vertebrate animal can restore normal function of its central nervous system (CNS after injury. Microglia accumulation at the damage site has been shown to be required for axon sprouting and for efficient regeneration. We characterized HmC1q as a novel chemotactic factor for leech microglial cell recruitment. In mammals, a C1q-binding protein (C1qBP alias gC1qR, which interacts with the globular head of C1q, has been reported to participate in C1q-mediated chemotaxis of blood immune cells. In this study, we evaluated the chemotactic activities of a recombinant form of HmC1q and its interaction with a newly characterized leech C1qBP that acts as its potential ligand. Methods Recombinant HmC1q (rHmC1q was produced in the yeast Pichia pastoris. Chemotaxis assays were performed to investigate rHmC1q-dependent microglia migration. The involvement of a C1qBP-related molecule in this chemotaxis mechanism was assessed by flow cytometry and with affinity purification experiments. The cellular localization of C1qBP mRNA and protein in leech was investigated using immunohistochemistry and in situ hybridization techniques. Results rHmC1q-stimulated microglia migrate in a dose-dependent manner. This rHmC1q-induced chemotaxis was reduced when cells were preincubated with either anti-HmC1q or anti-human C1qBP antibodies. A C1qBP-related molecule was characterized in leech microglia. Conclusions A previous study showed that recruitment of microglia is observed after HmC1q release at the cut end of axons. Here, we demonstrate that rHmC1q-dependent chemotaxis might be driven via a HmC1q-binding protein located on the microglial cell surface. Taken together, these results highlight the importance of the interaction between C1q and C1qBP in microglial activation leading to nerve repair in the medicinal

  15. Intestinal and Hepatic Niemann-Pick C1-Like 1

    Directory of Open Access Journals (Sweden)

    Sung-Woo Park

    2013-08-01

    Full Text Available Polytopic transmembrane protein, Niemann-Pick C1-Like 1 (NPC1L1 is localized at the apical membrane of enterocytes and the canalicular membrane of hepatocytes. It mediates intestinal cholesterol absorption and prevents extensive loss of cholesterol by transporting biliary cholesterol into hepatocytes. NPC1L1 is a molecular target of ezetimibe, an agent for hypercholesterolemia. Recently, NPC1L1 inhibition has been shown to prevent metabolic disorders such as fatty liver disease, obesity, diabetes, and atherosclerosis. In this review, the identification and characterization of NPC1L1, NPC1L1-dependent cholesterol transport, the relationship with pathogenesis of metabolic disease and its newly introduced function for virus entry are discussed.

  16. Plasma enhanced C1 chemistry for green technology

    Science.gov (United States)

    Nozaki, Tomohiro

    2013-09-01

    Plasma catalysis is one of the innovative next generation green technologies that meet the needs for energy and materials conservation as well as environmental protection. Non-thermal plasma uniquely generates reactive species independently of reaction temperature, and these species are used to initiate chemical reactions at unexpectedly lower temperatures than normal thermochemical reactions. Non-thermal plasma thus broadens the operation window of existing chemical conversion processes, and ultimately allows modification of the process parameters to minimize energy and material consumption. We have been specifically focusing on dielectric barrier discharge (DBD) as one of the viable non-thermal plasma sources for practical fuel reforming. In the presentation, room temperature one-step conversion of methane to methanol and hydrogen using a miniaturized DBD reactor (microplasma reactor) is highlighted. The practical impact of plasma technology on existing C1-chemistry is introduced, and then unique characteristics of plasma fuel reforming such as non-equilibrium product distribution is discussed.

  17. A Selection of Recent Advances in C1 Chemistry.

    Science.gov (United States)

    Mesters, Carl

    2016-06-01

    This review presents a selection of recent publications related to the chemistry and catalysis of C1 molecules, including methane, methanol, carbon monoxide, and carbon dioxide. These molecules play an important role in the current supply of energy and chemicals and will likely become even more relevant because of the need to decarbonize fuels (shift from coal to natural gas) in line with CO2 capture and use to mitigate global warming, as well as a gradual shift on the supply side from crude oil to natural gas. This review includes both recent industrial developments, such as the huge increase in methanol-to-olefins-capacity build in China and the demonstration of oxidative coupling of methane, and scientific developments in these chemistries facilitated by improved capabilities in, for example, analytical tools and computational modeling. PMID:27276549

  18. Thick-target yields of radioactive targets deduced from inverse kinematics

    International Nuclear Information System (INIS)

    The thick-target yield (TTY) is a macroscopic quantity reflected by nuclear reactions and matter properties of targets. In order to evaluate TTYs on radioactive targets, we suggest a conversion method from inverse kinematics corresponding to the reaction of radioactive beams on stable targets. The method to deduce the TTY is theoretically derived from inverse kinematics. We apply the method to the natCu(12C,X)24Na reaction to confirm availability. In addition, it is applied to the 137Cs + 12C reaction as an example of a radioactive system and discussed a conversion coefficient of a TTY measurement

  19. Intrinsic neutrino properties: As deduced from cosmology, astrophysics, accelerator and non-accelerator experiments

    International Nuclear Information System (INIS)

    I review the intrinsic properties of neutrinos as deduced from cosmological, astrophysical, and laboratory experiments. Bounds on magnetic moments and theoretical models which yield large moments but small masses are briefly discussed. The MSW solution to the solar neutrino problem is reviewed in light of the existing data from the 37Cl and Kamiokande II experiments. The combined data disfavor the adiabatic solution and tend to support either the large angle solution or the nonadiabatic one. In the former case the 71Ga signal will be suppressed by the same factor as for 37Cl, and in the latter case the suppression factor could be as large as 10 or more. 41 refs

  20. Radiation damage of the HEAO C-1 germanium detectors

    Science.gov (United States)

    Mahoney, W. A.; Ling, J. C.; Jacobson, A. S.

    1981-01-01

    The effects of radiation damage from proton bombardment of the four HEAO C-1 high purity germanium detectors have been measured and compared to predictions. Because of the presence of numerous gamma-ray lines in the detector background spectra and because of the relatively long exposure time of the HEAO 3 satellite to cosmic-ray and trapped protons, it has been possible to measure both the energy and time dependence of radiation damage. After 100 d in orbit, each of the four detectors has been exposed to approximately 3 x 10 to the 7th protons/sq cm, and the average energy resolution at 1460 keV had degraded from 3.2 keV fwhm to 8.6 keV fwhm. The lines were all broadened to the low energy side although the line profile was different for each of the four detectors. The damage-related contribution to the degradation in energy resolution was found to be linear in energy and proton influence.

  1. Structure of human Niemann-Pick C1 protein.

    Science.gov (United States)

    Li, Xiaochun; Wang, Jiawei; Coutavas, Elias; Shi, Hang; Hao, Qi; Blobel, Günter

    2016-07-19

    Niemann-Pick C1 protein (NPC1) is a late-endosomal membrane protein involved in trafficking of LDL-derived cholesterol, Niemann-Pick disease type C, and Ebola virus infection. NPC1 contains 13 transmembrane segments (TMs), five of which are thought to represent a "sterol-sensing domain" (SSD). Although present also in other key regulatory proteins of cholesterol biosynthesis, uptake, and signaling, the structure and mechanism of action of the SSD are unknown. Here we report a crystal structure of a large fragment of human NPC1 at 3.6 Å resolution, which reveals internal twofold pseudosymmetry along TM 2-13 and two structurally homologous domains that protrude 60 Å into the endosomal lumen. Strikingly, NPC1's SSD forms a cavity that is accessible from both the luminal bilayer leaflet and the endosomal lumen; computational modeling suggests that this cavity is large enough to accommodate one cholesterol molecule. We propose a model for NPC1 function in cholesterol sensing and transport. PMID:27307437

  2. [Hereditary angioneurotic edema: a molecular disease caused by a defect in the O-glycosylation of C1 esterase inhibitor (C1-INH)].

    Science.gov (United States)

    Ollier-Hartmann, M P; Strecker, G; Montreuil, J; Hartmann, L

    1984-01-01

    A quantitative and qualitative study of neutral and aminosaccharides in C 1-esterase inhibitor (C 1-INH), protein of the complement system, was performed. We observe a mixed glycosylation of the molecule with an N-glycosylated: O-glycosylated chain ratio of 1: 4. The loss of the inhibitory activity of the molecule in hereditary angioedema (O ANH) is associated with an O-glycosylation deficiency which differs according to the two molecular variants: C 1-INH (1 A) and C 1-INH (II) previously described. PMID:6440668

  3. Fission fragment mass yield deduced from density distribution in the pre-scission configuration

    CERN Document Server

    Warda, M

    2015-01-01

    Static self-consistent methods usually allow to determine the most probable fission fragments mass asymmetry. We have applied random neck rupture mechanism to the nuclei in the configuration at the end of fission paths. Fission fragment mass distributions have been deduced from the pre-scission nuclear density distribution obtained from the self-consistent calculations. Potential energy surfaces as well as nuclear shapes have been calculated in the fully microscopic theory, namely the constrained Hartree-Fock-Bogolubov model with the effective Gogny D1S density-dependent interaction. The method has been applied for analysis of fission of Fm-256,258, Cf-252 and Hg-180 and compared with the experimental data.

  4. Fission fragment mass yield deduced from density distribution in the pre-scission configuration

    Science.gov (United States)

    Warda, M.; Zdeb, A.

    2015-11-01

    Static self-consistent methods usually allow one to determine the most probable fission fragments mass asymmetry. We have applied random neck rupture mechanism to the nuclei in the configuration at the end of fission paths. Fission fragment mass distributions have been deduced from the pre-scission nuclear density distribution obtained from the self-consistent calculations. Potential energy surfaces as well as nuclear shapes have been calculated in the fully microscopic theory, namely the constrained Hartree-Fock-Bogoliubov model with the effective Gogny D1S density-dependent interaction. The method has been applied for analysis of fission of {}{256,258}Fm, 252Cf and 180Hg and compared with the experimental data.

  5. Behaviour of the Pleistocene marsupial lion deduced from claw marks in a southwestern Australian cave

    Science.gov (United States)

    Arman, Samuel D.; Prideaux, Gavin J.

    2016-01-01

    The marsupial lion, Thylacoleo carnifex, was the largest-ever marsupial carnivore, and is one of the most iconic extinct Australian vertebrates. With a highly-specialised dentition, powerful forelimbs and a robust build, its overall morphology is not approached by any other mammal. However, despite >150 years of attention, fundamental aspects of its biology remain unresolved. Here we analyse an assemblage of claw marks preserved on surfaces in a cave and deduce that they were generated by marsupial lions. The distribution and skewed size range of claw marks within the cave elucidate two key aspects of marsupial lion biology: they were excellent climbers and reared young in caves. Scrutiny of >10,000 co-located Pleistocene bones reveals few if any marsupial lion tooth marks, which dovetails with the morphology-based interpretation of the species as a flesh specialist. PMID:26876952

  6. Deducing ink thickness variations of fluorescent print by a spectral prediction model

    Science.gov (United States)

    Wang, Qingjuan; Zhang, Yixin; Tian, Dongwen

    2012-01-01

    In the color printing process, the thickness and uniformity of ink have a great affect on the color reproduction. The ink thickness uniformity is an important parameters of measuring the quality of printing. Based on the fluorescent additives may absorb ultraviolet light and exit blue light or visible light and by considering the expansion of the ink, optical properties of paper with fluorescent additives , the internal lateral spread of light in paper with fluorescent additives and the fluorescent Clapper-Yule spectral reflectance prediction model, we introduce two factor parameters which are the initial thickness of the inks and the factor of ink thickness variation. A model for deducing ink thickness variations of printing on the fluorescent substrate is developed by the least square method and the spectrum reflectance of prints which measures the ink thickness variations. The correctness of the conclusions are verified by experiment.

  7. Theoretical model to deduce a PDF with a power law tail using Extreme Physical Information

    CERN Document Server

    Bonilla, Ricardo; Valdivia, Juan Alejandro

    2011-01-01

    The theory of Extreme Physical Information (EPI) is used to deduce a probability density function (PDF) of a system that exhibits a power law tail. The computed PDF is useful to study and fit several observed distributions in complex systems. This new approach permits to describe extreme and rare events in the tail, and also the frequent events in the distribution head. Using EPI an information functional is constructed, and minimized using Euler-Lagrange equations. As a solution a second order differential equation is derived. By solving this equation a family of functions is calculated. These functions allow describing the system in terms of a eigenstates. A dissipative term is introduced into the model, as a relevant term to study open systems. One of the main results is a mathematical relation between the scaling parameter of the power law observed in the tail and the shape of the head.

  8. Hydrodynamic properties of gamma-ray bursts outflows deduced from thermal component

    CERN Document Server

    Pe'er, Asaf; O'Mahony, Shane; Margutti, Raffaella; Ryde, Felix; Larsson, Josefin; Lazzatti, Davide; Livio, Mario

    2015-01-01

    We study the properties of a significant thermal emission component that was identified in 47 GRBs observed by different instruments. Within the framework of the "fireball" model, we deduce the values of the Lorentz factor Gamma, and the acceleration radius, r_0, for these bursts. We find that all the values of Gamma in our sample are in the range 10^2 = 310. We find a very weak dependence of Gamma on the acceleration radius r_0, Gamma ~ r_0^alpha with alpha = -0.10 +- 0.09 at sigma = 2.1 confidence level. The values of r_0 span a wide range, 10^7 ~10^{8.5} cm. This is higher than the gravitational radius of a 10 M_sun black hole by a factor ~100. We argue that this result provides indirect evidence for jet propagation inside a massive star, and suggests the existence of recollimation shocks that take place close to this radius.

  9. Behaviour of the Pleistocene marsupial lion deduced from claw marks in a southwestern Australian cave.

    Science.gov (United States)

    Arman, Samuel D; Prideaux, Gavin J

    2016-01-01

    The marsupial lion, Thylacoleo carnifex, was the largest-ever marsupial carnivore, and is one of the most iconic extinct Australian vertebrates. With a highly-specialised dentition, powerful forelimbs and a robust build, its overall morphology is not approached by any other mammal. However, despite >150 years of attention, fundamental aspects of its biology remain unresolved. Here we analyse an assemblage of claw marks preserved on surfaces in a cave and deduce that they were generated by marsupial lions. The distribution and skewed size range of claw marks within the cave elucidate two key aspects of marsupial lion biology: they were excellent climbers and reared young in caves. Scrutiny of >10,000 co-located Pleistocene bones reveals few if any marsupial lion tooth marks, which dovetails with the morphology-based interpretation of the species as a flesh specialist. PMID:26876952

  10. Atmospheric phenomena deduced from radiosonde and GPS occultation measurements for various application related studies

    Indian Academy of Sciences (India)

    C J Johny; S K Sarkar; D Punyasesudu

    2009-02-01

    The tropopause height and tropopause temperature are sensitive to temperature changes in troposphere and stratosphere. These are the measures of global climatic variability. Atmospheric profiles of temperature, refractivity and water vapour are always needed for communication, navigation and atmospheric modeling studies. The tropopause characteristics over the Indian region have been studied using radio occultation measurements (CHAMP) on the basis of cold point criterion. Tropopause height shows large variation in the latitude range ∼30° –40°N during winter. Tropopause temperature less than −82°C, assumed to facilitate troposphere to stratosphere air transport, is observed at a number of tropical Indian locations and no seasonal pattern is observed in its occurrence. The bias in temperature and refractivity deduced from radiosonde and radio occultation measurements is also presented.

  11. The work function of n-ZnO deduced from heterojunctions with Si prepared by ALD

    Science.gov (United States)

    Quemener, V.; Alnes, M.; Vines, L.; Rauwel, P.; Nilsen, O.; Fjellvåg, H.; Monakhov, E. V.; Svensson, B. G.

    2012-08-01

    Highly doped n-type ZnO films have been grown on n-type and p-type Si substrates by atomic layer deposition (ALD). Transmission electron microscopy shows columnar growth of the ZnO films with randomly oriented grains and a very thin interfacial layer of SiOx(x ⩽ 2) with a thickness below 0.4 nm to the Si substrate. Current-voltage and capacitance-voltage measurements performed at temperatures from 50 to 300 K reveal a strong rectifying behaviour on both types of substrates with an ideality factor close to unity between 180 and 280 K. Using the classical approach of thermionic emission, the barrier heights of the ZnO/n-Si and ZnO/p-Si junctions have been deduced and consistent values are obtained yielding a work function of n-type ZnO close to 4.65 eV.

  12. Thick-target yields of radioactive targets deduced from inverse kinematics

    CERN Document Server

    Aikawa, Masayuki; Imai, Shotaro

    2014-01-01

    The thick-target yield (TTY) of long-lived fission products (LLFP) is an essential quantity and represents basic data for transmutation. In order to evaluate TTY on radioactive targets including LLFP, we suggest a conversion method from inverse kinematics corresponding to the reaction of radioactive beams on stable targets. We demonstrate the method to deduce the TTY from inverse kinematics derived from the theoretical definition. This method is highly applicable in reactions at the energy per nucleon \\epsilon > 20 MeV/A as practically confirmed by the simulation of the SRIM2008 code. In this paper, we apply the method to the natCu(12C,X)24Na reaction to confirm availability. In addition, it is applied to the 137Cs + 12C reaction to reduce 137Cs and to suggest a TTY measurement of the 137Cs induced reaction on a thick 12C target.

  13. Vortex magnetic structure in circularly magnetized microwires as deduced from magneto-optical Kerr measurements

    KAUST Repository

    Ivanov, Yurii P.

    2014-02-14

    The magneto-optic Kerr effect has been employed to determine the magnetization process and estimate the domain structure of microwires with circular magnetic anisotropy. The diameter of microwires was 8 μm, and pieces 2 cm long were selected for measurements. The analysis of the local surface longitudinal and transverse hysteresis loops has allowed us to deduce a vortex magnetic structure with axial core and circular external shell. Moreover, a bamboo-like surface domain structure is confirmed with wave length of around 10 to 15 μm and alternating chirality in adjacent circular domains. The width of the domain wall is estimated to be less than 3 μm. Finally, closure domain structures with significant helical magnetization component are observed extending up to around 1000 μm from the end of the microwire.

  14. Interaction of C1q and mannan-binding lectin (MBL) with C1r, C1s, MBL-associated serine proteases 1 and 2, and the MBL-associated protein MAp19

    DEFF Research Database (Denmark)

    Thiel, S; Petersen, Steen Vang; Vorup-Jensen, T; Matsushita, M; Fujita, T; Stover, C M; Schwaeble, W J; Jensenius, J C

    2000-01-01

    of C1r and C1s with C1q in that both high salt concentrations and calcium chelation (EDTA) are required to fully dissociate the MASPs or MAp19 from MBL. In the presence of calcium, most of the MASP-1, MASP-2, and MAp19 emerged on gel-permeation chromatography as large complexes that were not...... associated with MBL, whereas in the presence of EDTA most of these components formed smaller complexes. Over 95% of the total MASPs and MAp19 found in serum are not complexed with MBL. Udgivelsesdato: 2000-Jul-15...

  15. A survey on C 1,1 fuctions: theory, numerical methods and applications

    OpenAIRE

    La Torre Davide; Rocca Matteo

    2002-01-01

    In this paper we survey some notions of generalized derivative for C 1,1 functions. Furthermore some optimality conditions and numerical methods for nonlinear minimization problems involving C1,1 data are studied.

  16. Endotoxin-induced pulmonary dysfunction is prevented by C1-esterase inhibitor.

    OpenAIRE

    R. Guerrero; Velasco, F; M. Rodriguez; Lopez, A; Rojas, R; Alvarez, M A; Villalba, R.; V. Rubio; Torres, A.; del Castillo, D

    1993-01-01

    In septic shock, hypotension, disseminated intravascular coagulation, and neutrophil activation are related to the activation of the blood coagulation contact system. This study evaluates in dogs the effect of the C1-esterase inhibitor (C1-INH), a main inhibitor of the blood coagulation contact system, on the cardiovascular and respiratory dysfunction associated with endotoxic shock. Two groups were included: controls, which received Escherichia coli endotoxin, and a C1-INH group in which C1-...

  17. Serum IgG antibodies to C1q in hypocomplementemic urticarial vasculitis syndrome.

    Science.gov (United States)

    Wisnieski, J J; Naff, G B

    1989-09-01

    Urticaria, angioedema, and arthritis are cardinal features of hypocomplementemic urticarial vasculitis syndrome (HUVS). Considered to be an immune complex-mediated disorder, HUVS has been differentiated from systemic lupus erythematosus (SLE), based on its clinical manifestations and the C1q precipitin (C1q-p) reaction, which is manifested as gel precipitation of C1q by a small percentage of HUVS IgG molecules. This phenomenon has been attributed to an Fc region abnormality, and the responsible IgG molecules are said to possess C1q-p activity. We purified IgG from 4 HUVS patients and confirmed that HUVS IgG contains C1q binding activity. F(ab')2 fragments from these patients also bound to C1q, as measured by 2 different C1q binding methods at physiologic ionic strength; HUVS IgG Fc fragments did not bind to C1q. Preincubation of HUVS F(ab')2 fragments with antibody to human F(ab')2 prevented subsequent binding to C1q. We conclude that IgG antibodies to C1q are present in HUVS serum, and it is likely that these antibodies are C1q-p. Because the clinical manifestations of HUVS and the presence of anti-C1q antibodies have been described in patients with SLE, our findings support the concept that HUVS is an autoimmune syndrome related to SLE. PMID:2528353

  18. Safety of C1-Esterase Inhibitor in Acute and Prophylactic Therapy of Hereditary Angioedema

    DEFF Research Database (Denmark)

    Busse, Paula; Bygum, Anette; Edelman, Jonathan; Lumry, William; Machnig, Thomas; Martinez-Saguer, Inmaculada; Rojavin, Mikhail

    2014-01-01

    BACKGROUND: The plasma-derived, pasteurized C1-inhibitor (C1-INH) concentrate, Berinert has a 4-decade history of use in hereditary angioedema (HAE), with a substantial literature base that demonstrates safety and efficacy. Thromboembolic events have rarely been reported with C1-INH products...

  19. The role of ficolins and MASPs in hereditary angioedema due to C1-inhibitor deficiency

    DEFF Research Database (Denmark)

    Csuka, Dorottya; Munthe-Fog, Lea; Skjoedt, Mikkel-Ole; Kocsis, Andrea; Zotter, Zsuzsanna; Gál, Péter; Varga, Lilian; Farkas, Henriette; Füst, George; Garred, Peter

    Hereditary angioedema due to C1-inhibitor deficiency (HAE-C1-INH) causes disturbances in the complement system. However, the influence of HAE-C1-INH on the lectin pathway of complement is unresolved. Thus, we studied the main initiator molecules, enzymes and regulators in the lectin pathway in...

  20. Presence of C1-Inhibitor Polymers in a Subset of Patients Suffering from Hereditary Angioedema

    DEFF Research Database (Denmark)

    Elenius Madsen, Daniel; Hansen, Søren; Gram, Jørgen Brodersen; Bygum, Anette; Drouet, Christian; Sidelmann, Johannes Jakobsen

    2014-01-01

    Hereditary angioedema (HAE) is a potentially life-threatening disease caused by mutations in the gene encoding the serine protease inhibitor (serpin) C1 inhibitor (C1-inh). The mutations cause decreased functional plasma levels of C1-inh, which triggers unpredictable recurrent edema attacks...

  1. 26 CFR 1.860C-1 - Taxation of holders of residual interests.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 9 2010-04-01 2010-04-01 false Taxation of holders of residual interests. 1.860C-1 Section 1.860C-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Real Estate Investment Trusts § 1.860C-1 Taxation of...

  2. Anti-C1q Autoantibodies, Novel Tests, and Clinical Consequences

    OpenAIRE

    Mahler, Michael; van Schaarenburg, Rosanne A.; Trouw, Leendert A.

    2013-01-01

    Although anti-C1q autoantibodies have been described more than four decades ago a constant stream of papers describing clinical associations or functional consequences highlights that anti-C1q antibodies are still hot and happening. By far the largest set of studies focus on anti-C1q antibodies is systemic lupus erythematosus (SLE). In SLE anti-C1q antibodies associate with involvement of lupus nephritis in such a way that in the absence of anti-C1q antibodies it is unlikely that a flare in n...

  3. Human keratinocyte ATP2C1 localizes to the Golgi and controls Golgi Ca2+ stores

    OpenAIRE

    Behne, M J; Tu, Chia-Ling L; Aronchik, I; Epstein, E; Bench, G.; Bikle, D D; Pozzan, T; Mauro, T.M.

    2003-01-01

    Hailey-Hailey disease (MIM16960) is a blistering skin disease caused by mutations in the Ca2+ ATPase ATP2C1. We found that the abnormal Ca2+ signaling seen in Hailey-Hailey disease keratinocytes correlates with decreased protein levels of ATP2C1. Human ATP2C1 protein approximated 115 kDa in size. The ATP2C1 is localized to the Golgi apparatus in human keratinocytes, similar to its localization in yeast and Caenorhabditis elegans. To test whether the ATP2C1 controls Golgi Ca2+ stores, we measu...

  4. Treatment of hereditary angioedema with plasma-derived C1 inhibitor

    Directory of Open Access Journals (Sweden)

    Michael J Prematta

    2008-08-01

    Full Text Available Michael J Prematta, Tracy Prematta, Timothy J CraigSection of Allergy and Immunology, Penn State University, Milton S. Hershey Medical Center, PA, USABackground: Plasma-derived C1 inhibitor (C1-INH concentrate is a treatment option for acute hereditary angioedema (HAE attacks and is considered the standard-of-care in many countries, although it is not yet available in the United States. Studies are still being conducted to establish its safety and efficacy as required by the FDA.Objective: To review the medical literature to determine if C1-INH concentrate is a safe and effective treatment for acute HAE attacks.Methods: The following keywords were searched in PubMed and OVID: C1 esterase inhibitor, C1-inhibitor, C1 inhibitor, and hereditary angioedema treatment. English-language articles were searched from 1966 to the present to look for studies demonstrating the efficacy and the safety of C1-INH concentrate.Results: The English-language literature search revealed several studies showing significantly improved relief of HAE symptoms with the administration of C1-INH concentrate – many studies demonstrated some improvement of symptoms within 30 minutes. Side effects have been similar to placebo, and no proven cases of viral transmission have occurred in over 20 years.Conclusion: C1-INH concentrate appears to be a very safe and effective treatment option for HAE.Keywords: hereditary angioedema, c1 inhibitor, c1 esterase inhibitor, hereditary angioedema treatment

  5. Expression of aldo-keto reductase family 1 member C1 (AKR1C1 gene in porcine ovary and uterine endometrium during the estrous cycle and pregnancy

    Directory of Open Access Journals (Sweden)

    Hwang Sue-Yun

    2011-10-01

    Full Text Available Abstract Background The aldo-keto reductase family 1 member C1 (AKR1C1 belongs to a superfamily of NADPH-dependent reductases that convert a wide range of substrates, including carbohydrates, steroid hormones, and endogenous prostaglandins. The 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD is a member of AKR family. The aims of this study were to determine its expression in the ovary and uterus endometrium during the estrous cycle and pregnancy. Methods Rapid amplification of cDNA ends (RACE experiments were performed to obtain the 5' and 3' ends of the porcine 20alpha-HSD cDNA. Reverse-transcriptase-PCR (RT-PCR, real-time PCR, northern blot analysis, and western blot analysis were performed to examine the expression of porcine 20alpha-HSD. Immunohistochemical analysis was also performed to determine the localization in the ovary. Results The porcine 20alpha-HSD cDNA is 957 bp in length and encodes a protein of 319 amino acids. The cloned cDNA was virtually the same as the porcine AKR1C1 gene (337 amino acids reported recently, and only differed in the C-terminal region (the AKR1C1 gene has a longer C-terminal region than our sequence. The 20alpha-HSD gene (from now on referred to as AKR1C1 cloned in this paper encodes a deletion of 4 amino acids, compared with the C-terminal region of AKR1C1 genes from other animals. Porcine AKR1C1 mRNA was expressed on day 5, 10, 12, 15 of the cycle and 0-60 of pregnancy in the ovary. The mRNA was also specifically detected in the uterine endometrium on day 30 of pregnancy. Western blot analysis indicated that the pattern of AKR1C1 protein in the ovary during the estrous cycle and uterus during early pregnancy was similar to that of AKR1C1 mRNA expression. The recombinant protein produced in CHO cells was detected at approximately 37 kDa. Immunohistochemical analysis also revealed that pig AKR1C1 protein was localized in the large luteal cells in the early stages of the estrous cycle and before parturition

  6. Draft Genome Sequence of a Chitinase-producing Biocontrol Bacterium Serratia sp. C-1

    Directory of Open Access Journals (Sweden)

    Seur Kee Park

    2015-09-01

    Full Text Available The chitinase-producing bacterial strain C-1 is one of the key chitinase-producing biocontrol agents used for effective bioformulations for biological control. These bioformulations are mixed cultures of various chitinolytic bacteria. However, the precise identification, biocontrol activity, and the underlying mechanisms of the strain C-1 have not been investigated so far. Therefore, we evaluated in planta biocontrol efficacies of C-1 and determined the draft genome sequence of the strain in this study. The bacterial C-1 strain was identified as a novel Serratia sp. by a phylogenic analysis of its 16S rRNA sequence. The Serratia sp. C-1 bacterial cultures showed strong in planta biocontrol efficacies against some major phytopathogenic fungal diseases. The draft genome sequence of Serratia sp. C-1 indicated that the C-1 strain is a novel strain harboring a subset of genes that may be involved in its biocontrol activities.

  7. Angular Momentum Exchange Between Light and Material Media Deduced from the Doppler Shift

    CERN Document Server

    Mansuripur, Masud

    2013-01-01

    Electromagnetic waves carry energy as well as linear and angular momenta. When a light pulse is reflected from, transmitted through, or absorbed by a material medium, energy and momentum (both linear and angular) are generally exchanged, while the total amount of each entity remains intact. The extent of such exchanges between light and matter can be deduced, among other methods, with the aid of the Doppler shift phenomenon. The main focus of the present paper is on the transfer of angular momentum from a monochromatic light pulse to spinning objects such as a mirror, an absorptive dielectric, or a birefringent plate. The fact that individual photons of frequency omega carry energy in the amount of h_bar*omega, where h_bar is Planck's reduced constant, enables one to relate the Doppler shift to the amount of energy exchanged. Under certain circumstances, the knowledge of exchanged energy leads directly to a determination of the momentum transferred from the photon to the material body, or vice versa.

  8. PAS domain of the deduced Org35 protein mediates the interaction with NifA

    Institute of Scientific and Technical Information of China (English)

    TU Ran; CUI Yanhua; CHEN Sanfeng; LI Jilun

    2006-01-01

    NifA in Azospirillum brasilense plays a key role in regulating the synthesis of nitrogenase in response to ammonia and oxygen available. Recently,our laboratory has identified four clones, whose gene prodcuts interact with NifA, from A. brasilense Sp7genomic libraries by using the yeast two-hybrid system with NifA as bait. We are interested in clone S35,one of the four clones, because it contains a PAS-domain coding region. The entire open reading frame (ORF) for the PAS domain-containing protein was isolated and designated as org35 here. org35gene is 2211-bp long and encodes a protein of 736aa with a predicted molecular weight of about 78.4 kD.The predicted amino acid sequence of org35 has similarity to some two-component sensor kinase/response regulator hybrids of bacteria. Structural analyses showed that Org35 comprises at least three discrete conserved domains: the N-terminal PAS, the central histidine protein kinase (HPK) and the C-terminal response regulator (RR). The PAS domain of the deduced Org35 protein was found to interact directly with NifA, but the central HPK and the C-terminal RR domains of Org35 were not. These results indicated that interaction between NifA and Org35 was mediated by PAS domain.

  9. Epitopes of human testis-specific lactate dehydrogenase deduced from a cDNA sequence

    International Nuclear Information System (INIS)

    The sequence and structure of human testis-specific L-lactate dehydrogenase [LDHC4, LDHX; (L)-lactate:NAD+ oxidoreductase, EC 1.1.1.27] has been derived from analysis of a complementary DNA (cDNA) clone comprising the complete protein coding region of the enzyme. From the deduced amino acid sequence, human LDHC4 is as different from rodent LDHC4 (73% homology) as it is from human LDHA4 (76% homology) and porcine LDHB4 (68% homology). Subunit homologies are consistent with the conclusion that the LDHC gene arose by at least two independent duplication events. Furthermore, the lower degree of homology between mouse and human LDHC4 and the appearance of this isozyme late in evolution suggests a higher rate of mutation in the mammalian LDHC genes than in the LDHA and -B genes. Comparison of exposed amino acid residues of discrete anti-genic determinants of mouse and human LDHC4 reveals significant differences. Knowledge of the human LDHC4 sequence will help design human-specific peptides useful in the development of a contraceptive vaccine

  10. Function of longitudinal vs circular muscle fibers in esophageal peristalsis, deduced with mathematical modeling

    Institute of Scientific and Technical Information of China (English)

    James G Brasseur; Mark A Nicosia; Anupam Pal; Larr S Miller

    2007-01-01

    We summarize from previous works the functions of circular vs. longitudinal muscle in esophageal peristaltic bolus transport using a mix of experimental data, the conservation laws of mechanics and mathematical modeling. Whereas circular muscle tone generates radial closure pressure to create a local peristaltic closure wave, longitudinal muscle tone has two functions, one physiological with mechanical implications, and one purely mechanical. Each of these functions independently reduces the tension of individual circular muscle fibers to maintain closure as a consequence of shortening of longitudinal muscle locally coordinated with increasing circular muscle tone. The physiological function is deduced by combining basic laws of mechanics with concurrent measurements of intraluminal pressure from manometry, and changes in cross sectional muscle area from endoluminal ultrasound from which local longitudinal shortening (LLS) can be accurately obtained. The purely mechanical function of LLS was discovered from mathematical modeling of peristaltic esophageal transport with the axial wall motion generated by LLS. Physiologically, LLS concentrates circular muscle fibers where closure pressure is highest.However, the mechanical function of LLS is to reduce the level of pressure required to maintain closure. The combined physiological and mechanical consequences of LLS are to reduce circular muscle fiber tension and power by as much as 1/10 what would be required for peristalsis without the longitudinal muscle layer, a tremendous benefit that may explain the existence of longitudinal muscle fiber in the gut. We also review what is understood of the role of longitudinal muscle in esophageal emptying, reflux and pathology.

  11. Deducing the 237U(n,f) cross-section using the Surrogate Ratio Method

    Energy Technology Data Exchange (ETDEWEB)

    Burke, J T; Bernstein, L A; Escher, J; Ahle, L; Church, J A; Dietrich, F; Moody, K J; Norman, E B; Phair, L W; Fallon, P; Clark, R; Delaplanque, M; Descovich, M; Cromaz, M; Lee, I Y; Macchiavelli, A O; McMahan, M A; Moretto, L G; Rodriguez-Vieitez, E; Stephens, F S

    2005-08-16

    The authors have deduced the {sup 237}U(n,f) cross-section over an equivalent neutron energy range of 0 to 20 MeV using the Surrogate Ratio method. A 55 MeV {sup 4}He{sup 2+} beam from the 88 Inch Cyclotron at Lawrence Berkeley National Laboratory was used to induce fission in the following reactions {sup 238}U({alpha},{alpha}'f) and {sup 236}U({alpha},{alpha}'f). The {sup 238}U reaction was a surrogate for {sup 237}U(n,f) and the {sup 236}U reaction was used as a surrogate for {sup 235}U(n,f). The energies of the scattered alpha particles were detected in a fully depleted segmented silicon telescope array (STARS) over an angle range of 35{sup o} to 60{sup o} with respect to the beam axis. The fission fragments were detected in a third independent silicon detector located at backward angles between 106{sup o} to 131{sup o}.

  12. The Seismic risk perception in Italy deduced by a statistical sample

    Science.gov (United States)

    Crescimbene, Massimo; La Longa, Federica; Camassi, Romano; Pino, Nicola Alessandro; Pessina, Vera; Peruzza, Laura; Cerbara, Loredana; Crescimbene, Cristiana

    2015-04-01

    In 2014 EGU Assembly we presented the results of a web a survey on the perception of seismic risk in Italy. The data were derived from over 8,500 questionnaires coming from all Italian regions. Our questionnaire was built by using the semantic differential method (Osgood et al. 1957) with a seven points Likert scale. The questionnaire is inspired the main theoretical approaches of risk perception (psychometric paradigm, cultural theory, etc.) .The results were promising and seem to clearly indicate an underestimation of seismic risk by the italian population. Based on these promising results, the DPC has funded our research for the second year. In 2015 EGU Assembly we present the results of a new survey deduced by an italian statistical sample. The importance of statistical significance at national scale was also suggested by ISTAT (Italian Statistic Institute), considering the study as of national interest, accepted the "project on the perception of seismic risk" as a pilot study inside the National Statistical System (SISTAN), encouraging our RU to proceed in this direction. The survey was conducted by a company specialised in population surveys using the CATI method (computer assisted telephone interview). Preliminary results will be discussed. The statistical support was provided by the research partner CNR-IRPPS. This research is funded by Italian Civil Protection Department (DPC).

  13. Rates of intra- and intermolecular electron transfers in hydrogenase deduced from steady-state activity measurements.

    Science.gov (United States)

    Dementin, Sébastien; Burlat, Bénédicte; Fourmond, Vincent; Leroux, Fanny; Liebgott, Pierre-Pol; Abou Hamdan, Abbas; Léger, Christophe; Rousset, Marc; Guigliarelli, Bruno; Bertrand, Patrick

    2011-07-01

    Electrons are transferred over long distances along chains of FeS clusters in hydrogenases, mitochondrial complexes, and many other respiratory enzymes. It is usually presumed that electron transfer is fast in these systems, despite the fact that there has been no direct measurement of rates of FeS-to-FeS electron transfer in any respiratory enzyme. In this context, we propose and apply to NiFe hydrogenase an original strategy that consists of quantitatively interpreting the variations of steady-state activity that result from changing the nature of the FeS clusters which connect the active site to the redox partner, and/or the nature of the redox partner. Rates of intra- and intermolecular electron transfer are deduced from such large data sets. The mutation-induced variations of electron transfer rates cannot be explained by changes in intercenter distances and reduction potentials. This establishes that FeS-to-FeS rate constants are extremely sensitive to the nature and coordination of the centers. PMID:21615141

  14. F-region Pedersen conductivity deduced using the TIMED/GUVI limb retrievals

    Directory of Open Access Journals (Sweden)

    Y. Zhang

    2006-07-01

    Full Text Available As a proxy of the Rayleigh-Taylor instability growth rate for equatorial plasma bubbles, we investigate the flux-tube integrated F-region Pedersen conductivity (ΣPF using the electron density profiles (EDPs provided by the Global Ultraviolet Imager (GUVI on board the Thermosphere Ionosphere and Mesosphere Energetics and Dynamics (TIMED satellite. The investigation is conducted using the EDPs obtained in the Atlantic sector at 19:00-22:00 LT during 4–17 August and 6-16 December 2002. The seasonal difference of the strength and location of the equatorial ionization anomalies (EIAs induces a significant difference in the deduced ΣPF. Much stronger EIAs are created at higher altitudes and latitudes in December rather than in August. At 19:00–20:00 LT, the peak value of the ΣPF has 23 mhos at 1100 km apex height during 14–16 December and 18mhos at 600 km during 15–17 August. The ΣPF decreases as local time progresses. Therefore, ΣPF provides a preferred condition for the growth of bubbles to higher altitudes at 19:00-20:00 LT than at later hours, in December rather than in August in the Atlantic sector.

  15. Deducing conformational variability of intrinsically disordered proteins from infrared spectroscopy with Bayesian statistics

    International Nuclear Information System (INIS)

    Highlights: • Deduce secondary structure content of intrinsically disordered proteins from IR spectra. • Bayesian analysis to infer conformations of disordered regions of proteins from IR. • Comparison of measured and calculated IR spectra to obtain thermodynamic weights. - Abstract: As it remains practically impossible to generate ergodic ensembles for large intrinsically disordered proteins (IDP) with molecular dynamics (MD) simulations, it becomes critical to compare spectroscopic characteristics of the theoretically generated ensembles to corresponding measurements. We develop a Bayesian framework to infer the ensemble properties of an IDP using a combination of conformations generated by MD simulations and its measured infrared spectrum. We performed 100 different MD simulations totaling more than 10 μs to characterize the conformational ensemble of α-synuclein, a prototypical IDP, in water. These conformations are clustered based on solvent accessibility and helical content. We compute the amide-I band for these clusters and predict the thermodynamic weights of each cluster given the measured amide-I band. Bayesian analysis produces a reproducible and non-redundant set of thermodynamic weights for each cluster, which can then be used to calculate the ensemble properties. In a rigorous validation, these weights reproduce measured chemical shifts

  16. Bioinformatic identification of genes encoding C1q-domain containing proteins in zebrafish

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    C1q is the first subcomponent of classical pathway in the complement system and a major link between innate and acquired immunities. The globular (gC1q) domain similar with C1q was also found in many non-complement C1q-domain-containing (C1qDC) proteins which have similar crystal structure to that of the multifunctional tumor necrosis factor (TNF) ligand family, and also have diverse functions. In this study, we identified a total of 52 independent gene sequences encoding C1q-domain-containing proteins through comprehensive searches of zebrafish genome, cDNA and EST databases. In comparison to 31 orthologous genes in human and different numbers in other species, a significant selective pressure was suggested during vertebrate evolution. Domain organization of C1q-domain-containing (C1qDC) proteins mainly includes a leading signal peptide, a collagen-like region of variable length, and a C-terminal C1q domain. There are 11 highly conserved residues within the C1q domain, among which 2 are invariant within the zebrafish gene set. A more extensive database searches also revealed homologous C1qDC proteins in other vertebrates, invertebrates and even bacterium, but no homologous sequences for encoding C1qDC proteins were found in many species that have a more recent evolutionary history with zebrafish. Therefore, further studies on C1q-domain-containing genes among different species will help us understand evolutionary mechanism of innate and acquired immunities.

  17. Enzymatic pathways in the pathogenesis of hereditary angioedema: the role of C1 inhibitor therapy.

    Science.gov (United States)

    Kaplan, Allen P

    2010-11-01

    A functional abnormality of C1 inhibitor (C1INH) is present in types I and II hereditary angioedema (HAE), and normal C1INH may be rendered ineffective in the newly described type III HAE. C1INH inhibits factor XIIa, factor XII fragment (XIIf), kallikrein, and plasmin. Thus, in its absence, there is marked activation of the bradykinin-forming cascade resulting in severe angioedema. Factor XII may autoactivate on binding to endothelial cell surface gC1qR (receptor for the globular heads of C1q) thus initiating the cascade. Alternatively, stimuli that activate endothelial cells may liberate (or express at the cell surface) heat shock protein 90 or the enzyme prolylcarboxypeptidase, either of which can interact with the prekallikrein-high-molecular-weight kininogen complex to convert prekallikrein to kallikrein stoichiometrically. The kallikrein produced can cleave high-molecular-weight kininogen to produce bradykinin and also recruit factor XII by enzymatically activating it. Patients with type I or II HAE have mutant C1INH so that control of C1 activation is lost. Autoactivation of C1r in the absence of C1INH leads to C1s activation followed by C4 cleavage and depletion. An attack of swelling is accompanied by conversion of factor XIIa to factor XIIf and further enzymatic activation of C1r so that C4 levels drop further and C2 is depleted. New therapies for HAE focus on the bradykinin-forming cascade and include a kallikrein inhibitor and a bradykinin B-2 receptor antagonist in addition to administration of purified C1INH. PMID:20889195

  18. The importance of polarizability: comparison of models of carbon disulphide in the ionic liquids [C1C1im][NTf2] and [C4C1im][NTf2].

    Science.gov (United States)

    Lynden-Bell, Ruth M; Quitevis, Edward L

    2016-06-28

    The local environment of CS2 and in solution in two ionic liquids ([C1C1im][NTf2] and [C4C1im][NTf2]) are investigated by atomistic simulation and compared with that in neat CS2. The intermolecular vibrational densities of states of CS2 are calculated and compared with experimental OHD-RIKES spectra. The fair agreement of the results from solutions but poor agreement of the results from neat CS2 suggest that while collective effects are unimportant in solutions, they have a major effect on the OHD-RIKES spectrum of neat CS2. Comparing polarizable and unpolarizable models for CS2 emphasizes the importance of polarizability in determining local structure. PMID:27273458

  19. Cell surface expression and function of the macromolecular C1 complex on the surface of human monocytes

    Directory of Open Access Journals (Sweden)

    Kinga K Hosszu

    2012-03-01

    Full Text Available The synthesis of the subunits of the C1 complex (C1q, C1s, C1r, and its regulator C1 inhibitor (C1-Inh by human monocytes has been previously established. However, surface expression of these molecules by monocytes has not been shown. Using flow cytometry and antigen-capture ELISA, we show here for the first time that, in addition to C1q, PB monocytes and the monocyte-derived U937 cells express C1s and C1r, as well as Factor B and C1-Inh on their surface. C1s and C1r immunoprecipitated with C1q, suggesting that at least some of the C1q on these cells is part of the C1 complex. Furthermore, the C1 complex on U937 cells was able to trigger complement activation via the classical pathway. The presence of C1-Inh may ensure that an unwarranted autoactivation of the C1 complex does not take place. Since C1-Inh closely monitors the activation of the C1 complex in a sterile or infectious inflammatory environment, further elucidation of the role of C1 complex is crucial to dissect its function in monocyte, DC and T cell activities, and its implications in host defense and tolerance.

  20. Production and characterization of a murine monoclonal IgM antibody to human C1q receptor (C1qR)

    International Nuclear Information System (INIS)

    A hybridoma cell line that produces a monoclonal antibody (MAb) to cell surface C1q receptor (C1qr) has been produced by fusion of the P3 x 63-Ag8.653 mouse myeloma cell line with the spleen cells of a CD-1 mouse that had been hyperimmunized with viable Raji cell suspensions (5 x 107 cells/inoculum). This MAb, designated II1/D1, is an IgM antibody with lambda-light chain specificity. Radiolabeled or unlabeled, highly purified II1/D1 was used to determine that: a) this antibody competes for C1q binding sites on C1qR-bearing cells; b) the molecule recognized by this MAb is the C1qR; and c) cells that are known to bind C1q also bind II1/D1 in a specific manner. Western blot analysis of solubilized Raji, or U937 cell membranes, showed that the 125I-MAb detected a major protein band of approximately 85000 m.w. in its unreduced state, indicating that the C1qR is similar, if not identical, in both types of cells. Analyses of 125I-II/D1 binding experiments revealed that the antibody bound to Raji cells or u937 cells in a specific manner. Uptake of the antibody was saturable, with equilibrium virtually attained within 35 min. Scatchard analysis of the binding data using the intact MAb suggests that the affinity constant K/sub D/ is 2.9 x 10-10 M, and at apparent saturation, 24.6 ng of the antibody were bound per 2 x 106 cells, giving an estimated 7.8 x 103 antibody molecules bound per cell. That the II1/D1 antibody is specifically directed to the C1q was further evidenced by an ELISA in which the ability of C1qR-bearing cells to bind the MAb was abrogated by c-C1q in a specific dose-dependent manner

  1. Zonal currents in the F region deduced from Swarm constellation measurements

    Science.gov (United States)

    Lühr, Hermann; Kervalishvili, Guram; Rauberg, Jan; Stolle, Claudia

    2016-01-01

    The Swarm constellation has been used to estimate zonal currents in the topside F region ionosphere at about 500 km. Near-simultaneous magnetic field measurements from two altitudes but the same meridian are used for the current density calculations. We consider the period 15 February to 23 June 2014 for deriving a full 24 h local time coverage of the latitudinal distribution over ±50° in magnetic latitude. Intervals with close orbital phasing at the two heights are considered, which repeat every 6 days. From such days seven successive orbits are used where the epochs of equator crossings differ by less than 2 min. Deduced current densities are predominantly eastward (about 20 nA/m2) on the dayside and westward (about 10 nA/m2) on the nightside. A number of different drivers contribute to the observed total current. We identified the gravity-driven eastward current as the most prominent at low latitudes. Eastward currents in the Northern Hemisphere are clearly stronger than in the south. This is attributed to the proximity of our study period to June solstice, when the solar radiation is stronger in the north. In addition, interhemispheric winds from the Northern (summer) to the Southern (winter) Hemisphere contribute. They cause eastward currents in the north and westward in the south. We find a relatively large variability of the zonal currents both in space and time. The standard deviation is at least twice as large as the mean value of current density. This large variability is suggested to be related to gravity wave forcing from below.

  2. Nuclear structure of light thallium isotopes as deduced from laser spectroscopy on a fast atom beam

    International Nuclear Information System (INIS)

    After optimizing the system by experiments on /sup 201,203,205/Tl, the neutron-deficient isotopes 189-193Tl have been studied using the collinear fast atom beam laser spectroscopy system at UNISOR on-line to the Holifield Heavy Ion Research Facility. A sensitive system for the measurements was developed since the light isotopes were available in mass-separated beams of only 7 x 104 to 4 x 105 atoms per second. By laser excitation of the 535 nm atomic transitions of atoms in the beam, the 6s27s 2S/sub 1/2/ and 6s26s 2P/sub 3/2/ hyperfine structures were measured, as were the isotope shifts of the 535 nm transitions. From these, the magnetic dipole moments, spectroscopic quadrupole moments and isotopic changes in mean-square charge radius were deduced. The magnetic dipole moments are consistent with previous data. The /sup 190,192/Tl isotopes show a considerable difference in quadrupole deformations as well as an anomalous isotope shift with respect to 194Tl. A large isomer shift in 193Tl is observed implying a larger deformation in the 9/2- isomer than in the 1/2+ ground state. The /sup 189,191,193/Tl isomers show increasing deformation away from stability. A deformed shell model calculation indicates that this increase in deformation can account for the dropping of the 9/2- band in these isotopes while an increase in neutron pairing correlations, having opposite and compensating effects on the rotational moment of inertia, maintains the 9/2- strong-coupled band structure. 105 refs., 27 figs

  3. A novel computational framework for deducing muscle synergies from experimental joint moments

    Directory of Open Access Journals (Sweden)

    Anantharaman eGopalakrishnan

    2014-12-01

    Full Text Available Prior experimental studies have hypothesized the existence of a ‘muscle synergy’ based control scheme for producing limb movements and locomotion in vertebrates. Such synergies have been suggested to consist of fixed muscle grouping schemes with the co-activation of all muscles in a synergy resulting in limb movement. Quantitative representations of these groupings (termed muscle weightings and their control signals (termed synergy controls have traditionally been derived by the factorization of experimentally measured EMG. This study presents a novel approach for deducing these weightings and controls from inverse dynamic joint moments that are computed from an alternative set of experimental measurements – movement kinematics and kinetics. This technique was applied to joint moments for healthy human walking at 0.7 and 1.7 m/s, and two sets of ‘simulated’ synergies were computed based on two different criteria (1 synergies were required to minimize errors between experimental and simulated joint moments in a musculoskeletal model (pure-synergy solution (2 along with minimizing joint moment errors, synergies also minimized muscle activation levels (optimal-synergy solution. On comparing the two solutions, it was observed that the introduction of optimality requirements (optimal-synergy to a control strategy solely aimed at reproducing the joint moments (pure-synergy did not necessitate major changes in the muscle grouping within synergies or the temporal profiles of synergy control signals. Synergies from both the simulated solutions exhibited many similarities to EMG derived synergies from a previously published study, thus implying that the analysis of the two different types of experimental data reveals similar, underlying synergy structures.

  4. Marked variability in clinical presentation and outcome of patients with C1q immunodeficiency

    DEFF Research Database (Denmark)

    van Schaarenburg, Rosanne A; Schejbel, Lone; Truedsson, Lennart;

    2015-01-01

    OBJECTIVE: Globally approximately 60 cases of C1q deficiency have been described with a high prevalence of Systemic Lupus Erythematosus (SLE). So far treatment has been guided by the clinical presentation rather than the underlying C1q deficiency. Recently, it was shown that C1q production can be...... restored by allogeneic hematopoietic stem cell transplantation. Current literature lacks information on disease progression and quality of life of C1q deficient persons which is of major importance to guide clinicians taking care of patients with this rare disease. METHODS: We performed an international...... survey, of clinicians treating C1q deficient patients. A high response rate of >70% of the contacted clinicians yielded information on 45 patients with C1q deficiency of which 25 are published. RESULTS: Follow-up data of 45 patients from 31 families was obtained for a median of 11 years after diagnosis...

  5. Draft Genome Sequence of a Chitinase-producing Biocontrol Bacterium Serratia sp. C-1

    OpenAIRE

    Seur Kee Park; Young Cheol Kim

    2015-01-01

    The chitinase-producing bacterial strain C-1 is one of the key chitinase-producing biocontrol agents used for effective bioformulations for biological control. These bioformulations are mixed cultures of various chitinolytic bacteria. However, the precise identification, biocontrol activity, and the underlying mechanisms of the strain C-1 have not been investigated so far. Therefore, we evaluated in planta biocontrol efficacies of C-1 and determined the draft genome sequence of the strain in ...

  6. Contribution of the Federal Republic of Germany to chapter C.1

    International Nuclear Information System (INIS)

    The paper is a summary of two more detailed reports, covering the chapters of the WG 5 - C report C.1.3, C.1.4, C.1.5, and C.1.6. The main results of the investigations are that no environmental and ecological problems specific of FBR exist in comparison to thermal reactors. The ecological impact of spent fuel is quantified by generally adapted measures such as the ''Hazard Measure''. It is demonstrated that e.g. the ingestion ''Hazard Measure'' of the FBR over cooling times ranging from 0 to 106 years is lower than that of LWR once-through systems

  7. Receptor-mediated binding of C1 q on pulmonary endothelial cells

    International Nuclear Information System (INIS)

    Normal undamaged pulmonary endothelial cells (EC) do not express receptors for C3b or the Fc portion of IgG, but both receptors become unmasked after viral infection or exposure to white cell lysates. Here, highly purified human C1q was labeled with 125I, and the globular subunits were separated from the collagenous portion by collagenase digestion and chromatography. Bovine pulmonary artery EC were cultured without exposure to proteolytic enzymes. Binding assays were carried out at 00C, pH 7.4, μ = 0.15. Results showed that 125I-C1q binds to EC, the binding is dose-dependent, and the receptor is saturable. Saturation was approached at a C1q concentration of ca 0.1 ug. By Scatchard analysis, maximum binding was 0.219 pmoles in a volume of 250 μl for 7 x 105 cells, and the average number of binding sites per cell was 1.88 x 105. Isolated 125I-C1q heads do not bind, and when native 125I-C1q was bound to EC radioactivity was eliminated after collagenase treatment for 4 h at 370C. Thus, C1q binds to EC via the collagenous portion. That Fc receptors (globular heads) are exposed was shown by rosette formation with EA and EC bound C1q. Using similar conditions, native C1(C1w x 2C1r x 2C1s) did not bind to EC. These results suggest a mechanism for localizing immune complexes on undamaged pulmonary vessels which may be important for initiation of the inflammatory response

  8. The C1q family of proteins: insights into the emerging non-traditional functions

    Directory of Open Access Journals (Sweden)

    Berhane eGhebrehiwet

    2012-04-01

    Full Text Available Research conducted over the past 20 years have helped us unravel not only the hidden structural and functional subtleties of human C1q, but also has catapulted the molecule from a mere recognition unit of the classical pathway to a well-recognized molecular sensor of damage modified self or non-self antigens. Thus, C1q is involved in a rapidly expanding list of pathological disorders—including autoimmunity, trophoblast migration, preeclampsia and cancer. The results of two recent reports are provided to underscore the critical role C1q plays in health and disease. First is the observation by Singh and colleagues showing that pregnant C1q-/- mice recapitulate the key features of human preeclampsia that correlate with increased fetal death. Treatment of the C1q-/- mice with pravastatin restored trophoblast invasiveness, placental blood flow, and angiogenic balance and, thus, prevented the onset of preeclampsia. Second is the report by Hong et al., which showed that C1q can induce apoptosis of prostate cancer cells by activating the tumor suppressor molecule WW-domain containing oxydoreductase (WWOX or WOX1 and destabilizing cell adhesion. Downregulation of C1q on the other hand enhanced prostate hyperplasia and cancer formation due to failure of WOX1 activation. Recent evidence also shows that C1q belongs to a family of structurally and functionally related TNFα-like family of proteins that may have arisen from a common ancestral gene. Therefore C1q not only shares the diverse functions with the TNF family of proteins, but also explains why C1q has retained some of its ancestral cytokine-like activities. This review is intended to highlight some of the structural and functional aspects of C1q by underscoring the growing list of its non-traditional functions.

  9. Tropospheric CO vertical profiles deduced from total columns using data assimilation: methodology and validation

    Directory of Open Access Journals (Sweden)

    L. El Amraoui

    2013-07-01

    Full Text Available This paper presents a validation of a method to derive the vertical profile of carbon monoxide (CO from its total column using data assimilation. The main motivation of this study is twofold. First, to deduce both the vertical CO profiles and the assimilated CO fields with good confidence. Second, for chemical species that can be measured only as the total column, this method provides an attractive alternative for estimating their vertical profiles in the troposphere. We choose version 3 (V3 of MOPITT CO total columns to validate the proposed method. MOPITT has the advantage of providing both the vertical profiles and the total columns of CO. Furthermore, this version has been extensively validated by comparison with many independent datasets, and has been used in many scientific studies. The first step of the paper consists in the specification of the observation errors based on the Chi-square (χ2 test. The observations have been binned according to day, night, land and sea (LAND_DAY, LAND_NIGHT and SEA, respectively. The respective optimal observation error values for which the χ2 metric is the closest to 1 are: 7%, 8% and 11% for SEA, LAND_DAY and LAND_NIGHT, respectively. In a second step, the CO total column, with its specified errors, is used within the assimilation system to estimate the vertical profiles. These are validated by comparison with vertical profiles of MOPITT V3 retrievals at global and regional scales. Generally, both datasets show similar patterns and good agreement at both global and regional scales. Nevertheless, the total column analyses (TOTCOL_ANALYSES slightly overestimate CO concentrations compared to MOPITT observations. In a third step, vertical profiles calculated from TOTCOL_ANALYSES have been compared to those calculated from the assimilation of MOPITT V3 vertical profiles (PROFILE_ANALYSES. Both datasets shows very good agreement, but TOTCOL_ANALYSES tend to slightly overestimate CO concentrations. The mean

  10. Active deformation processes of the Northern Caucasus deduced from the GPS observations

    Science.gov (United States)

    Milyukov, Vadim; Mironov, Alexey; Rogozhin, Eugeny; Steblov, Grigory; Gabsatarov, Yury

    2015-04-01

    The Northern Caucasus, as a part of the Alpine-Himalayan mobile belt, is a zone of complex tectonics associated with the interaction of the two major tectonic plates, Arabian and Eurasian. The first GPS study of the contemporary geodynamics of the Caucasus mountain system were launched in the early 1990s in the framework of the Russia-US joint project. Since 2005 observations of the modern tectonic motion of the Northern Caucasus are carried out using the continuous GPS network. This network encompasses the territory of three Northern Caucasian Republics of the Russian Federation: Karachay-Cherkessia, Kabardino-Balkaria, and North Ossetia. In the Ossetian part of the Northern Caucasus the network of GPS survey-mode sites has been deployed as well. The GPS velocities confirm weak general compression of the Northern Caucasus with at the rate of about 1-2 mm/year. This horizontal motion at the boundary of the Northern Caucasus with respect to the Eurasian plate causes the higher seismic and tectonic activity of this transition zone. This result confirms that the source of deformation of the Northern Caucasus is the sub-meridional drift of the Arabian plate towards the adjacent boundary of the Eastern European part of the Eurasian lithospheric plate. The concept of such convergence implies that the Caucasian segment of the Alpine-Himalayan mobile belt is under compression, the layers of sedimentary and volcanic rocks are folded, the basement blocks are subject to shifts in various directions, and the upper crust layers are ruptured by reverse faults and thrusts. Weak deviation of observed velocities from the pattern corresponding to homogeneous compression can also be revealed, and numerical modeling of deformations of major regional tectonic structures, such as the Main Caucasus Ridge, can explain this. The deformation tensor deduced from the velocity field also exhibits the sub-meridional direction of the major compressional axes which coincides with the direction of

  11. C1-curved finite elements with numerical integration for thin plate and thin shell problems : part 1 : construction and interpolation properties of curved C1 finite elements

    OpenAIRE

    Bernadou, Michel

    1992-01-01

    The purpose of this paper is to construct curved finite elements of class C1 compatible with the elements of Argyris-Fried-Scharpf and Bell. We start by the approximation of the curved boundary and next, we construct curved finite elements of class C1. We conclude by proving that the correspond- ing asymptotic interpolation error has the same order than for the associate straight elements. In the second part of this work, we will study the approximation of thin plate and thin shell problems b...

  12. Genetic analysis of complement C1s deficiency associated with systemic lupus erythematosus highlights alternative splicing of normal C1s gene

    DEFF Research Database (Denmark)

    Armano, MT; Ferriani, VP; Florido, MP;

    2008-01-01

    ' fibroblasts when analyzed by confocal microscopy. We show that all four siblings are homozygous for a mutation at position 938 in exon 6 of the C1s cDNA that creates a premature stop codon. Our investigations led us to reveal the presence of previously uncharacterized splice variants of C1s mRNA transcripts...... in normal human cells. These variants are derived from the skipping of exon 3 and from the use of an alternative 3' splice site within intron 1 which increases the size of exon 2 by 87 nucleotides....

  13. On the LTSN solution of the transport equation in a slab for c=1

    International Nuclear Information System (INIS)

    In this work we present a LTSN formulation for the isotropic neutron transport problem in a slab assuming c = 1. We modify the LTSN solution encoding the Case solution for c = 1 by the application of the combined Schur decomposition and Heaviside expansion techniques. We also report numerical results. (author)

  14. Autoantibodies against C1q in systemic lupus erythematosus are antigen-driven

    DEFF Research Database (Denmark)

    Schaller, Monica; Bigler, Cornelia; Danner, Doris;

    2009-01-01

    Autoantibodies against complement C1q (anti-C1q Abs) were shown to strongly correlate with the occurrence of severe nephritis in patients with systemic lupus erythematosus (SLE), suggesting a potential pathogenic role by interfering with the complement cascade. To analyze the humoral immune...

  15. 26 CFR 1.641(c)-1 - Electing small business trust.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Electing small business trust. 1.641(c)-1...) INCOME TAX (CONTINUED) INCOME TAXES Estates, Trusts, and Beneficiaries § 1.641(c)-1 Electing small business trust. (a) In general. An electing small business trust (ESBT) within the meaning of section...

  16. 26 CFR 40.6302(c)-1 - Use of Government depositaries.

    Science.gov (United States)

    2010-04-01

    ... in 31 CFR part 203). (2) Deposits by electronic funds transfer. For the requirement to deposit excise... 26 Internal Revenue 16 2010-04-01 2010-04-01 true Use of Government depositaries. 40.6302(c)-1...) MISCELLANEOUS EXCISE TAXES EXCISE TAX PROCEDURAL REGULATIONS § 40.6302(c)-1 Use of Government depositaries....

  17. Functional C1-inhibitor diagnostics in hereditary angioedema: assay evaluation and recommendations

    DEFF Research Database (Denmark)

    Wagenaar-Bos, Ineke G A; Drouet, Christian; Aygören-Pursun, Emel;

    2008-01-01

    Hereditary angioedema (HAE) is an autosomal dominant disease characterized by recurrent episodes of potentially life-threatening angioedema. The most widespread underlying genetic deficiency is a heterozygous deficiency of the serine protease inhibitor C1 esterase inhibitor (C1-Inh). In addition ...

  18. C1-inhibitor polymers activate the FXII-dependent kallikrein-kinin system

    DEFF Research Database (Denmark)

    Elenius Madsen, Daniel; Sidelmann, Johannes Jakobsen; Biltoft, Daniel; Gram, Jørgen Brodersen; Hansen, Søren

    2015-01-01

    BACKGROUND: The FXII-dependent kallikrein-kinin system (KKS) is tightly regulated by the serine protease inhibitor (serpin) C1-inhibitor (C1-inh). When regulation of the FXII-dependent KKS fails, which is the case in hereditary angioedema (HAE), patients consequently experience invalidating edema...

  19. 26 CFR 301.6323(c)-1 - Protection for commercial transactions financing agreements.

    Science.gov (United States)

    2010-04-01

    ... is any right to payment for goods sold or leased or for services rendered which is not evidenced by... financing agreements. 301.6323(c)-1 Section 301.6323(c)-1 Internal Revenue INTERNAL REVENUE SERVICE... the tax lien filing, (2) Is in qualified property covered by the terms of a commercial...

  20. Differential regulation of Aβ42-induced neuronal C1q synthesis and microglial activation

    Directory of Open Access Journals (Sweden)

    Tenner Andrea J

    2005-01-01

    Full Text Available Abstract Expression of C1q, an early component of the classical complement pathway, has been shown to be induced in neurons in hippocampal slices, following accumulation of exogenous Aβ42. Microglial activation was also detected by surface marker expression and cytokine production. To determine whether C1q induction was correlated with intraneuronal Aβ and/or microglial activation, D-(--2-amino-5-phosphonovaleric acid (APV, an NMDA receptor antagonist and glycine-arginine-glycine-aspartic acid-serine-proline peptide (RGD, an integrin receptor antagonist, which blocks and enhances Aβ42 uptake, respectively, were assessed for their effect on neuronal C1q synthesis and microglial activation. APV inhibited, and RGD enhanced, microglial activation and neuronal C1q expression. However, addition of Aβ10–20 to slice cultures significantly reduced Aβ42 uptake and microglial activation, but did not alter the Aβ42-induced neuronal C1q expression. Furthermore, Aβ10–20 alone triggered C1q production in neurons, demonstrating that neither neuronal Aβ42 accumulation, nor microglial activation is required for neuronal C1q upregulation. These data are compatible with the hypothesis that multiple receptors are involved in Aβ injury and signaling in neurons. Some lead to neuronal C1q induction, whereas other(s lead to intraneuronal accumulation of Aβ and/or stimulation of microglia.

  1. Complement protein C1q induces maturation of human dendritic cells

    DEFF Research Database (Denmark)

    Cosmor, E; Bajtay, Z; Sándor, N;

    2007-01-01

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

  2. C1GALT1 enhances proliferation of hepatocellular carcinoma cells via modulating MET glycosylation and dimerization.

    Science.gov (United States)

    Wu, Yao-Ming; Liu, Chiung-Hui; Huang, Miao-Juei; Lai, Hong-Shiee; Lee, Po-Huang; Hu, Rey-Heng; Huang, Min-Chuan

    2013-09-01

    Altered glycosylation is a hallmark of cancer. The core 1 β1,3-galactosyltransferase (C1GALT1) controls the formation of mucin-type O-glycans, far overlooked and underestimated in cancer. Here, we report that C1GALT1 mRNA and protein are frequently overexpressed in hepatocellular carcinoma tumors compared with nontumor liver tissues, where it correlates with advanced tumor stage, metastasis, and poor survival. Enforced expression of C1GALT1 was sufficient to enhance cell proliferation, whereas RNA interference-mediated silencing of C1GALT1 was sufficient to suppress cell proliferation in vitro and in vivo. Notably, C1GALT1 attenuation also suppressed hepatocyte growth factor (HGF)-mediated phosphorylation of the MET kinase in hepatocellular carcinoma cells, whereas enforced expression of C1GALT1 enhanced MET phosphorylation. MET blockade with PHA665752 inhibited C1GALT1-enhanced cell viability. In support of these results, we found that the expression level of phospho-MET and C1GALT1 were associated in primary hepatocellular carcinoma tissues. Mechanistic investigations showed that MET was decorated with O-glycans, as revealed by binding to Vicia villosa agglutinin and peanut agglutinin. Moreover, C1GALT1 modified the O-glycosylation of MET, enhancing its HGF-induced dimerization and activation. Together, our results indicate that C1GALT1 overexpression in hepatocellular carcinoma activates HGF signaling via modulation of MET O-glycosylation and dimerization, providing new insights into how O-glycosylation drives hepatocellular carcinoma pathogenesis. PMID:23832667

  3. Separation and conductimetric detection of C1-C7 aliphatic monocarboxylic acids and C1-C7 aliphatic monoamines on unfunctionized polymethacrylate resin columns.

    Science.gov (United States)

    Ohta, Kazutoku; Towata, Atsuya; Ohashi, Masayoshi; Takeuchi, Toyohide

    2004-06-11

    The application of unfunctionized polymethacrylate resin (TSKgel G3000PWXL) as a stationary phase in liquid chromatography with conductimetric detection for C1-C7 aliphatic monocarboxylic acids (formic acid, acetic acid, propionic acid, butyric acid, isovaleric acid, valeric acid, 3,3-dimethylbutyric acid, 4-methylvaleric acid, hexanoic acid, 2-methylhexanoic acid, 5-methylhexanoic acid and heptanoic acid) and C1-C7 aliphatic monoamines (methylamine, ethylamine, propylamine, isobutylamine, butylamine, isoamylamine, amylamine, 1,3-dimethylbutylamine, hexylamine, 2-heptylamine and heptylamine) was attempted with C8 aliphatic monocarboxylic acids (2-propylvaleric acid, 2-ethylhexanoic acid, 2-methylheptanoic acid and octanoic acid) and C8 aliphatic monoamines (1,5-dimethylhexylamine, 2-ethylhexylamine, 1-methylheptylamine and octylamine) as eluents, respectively. Using 1 mM 2-methylheptanoic acid at pH 4.0 as the eluent, excellent separation and relatively high sensitive detection for these C1-C7 carboxylic acids were achieved on a TSKgel G3000PWXL column (150 mm x 6 mm i.d.) in 60 min. Using 2 mM octylamine at pH 11.0 as the eluent, excellent separation and relatively high sensitive detection for these C1-C7 amines were also achieved on the TSKgel G3000PWXL column in 60 min. PMID:15250420

  4. Experimental investigation on the combined use of C1O2 and NaC1O for drinking water treatment

    International Nuclear Information System (INIS)

    In Italy, most of the plants producing water for human consumption, use Chlorine Dioxide (C1O2) and Sodium Hypochlorite (NaC1O) for the oxidation and disinfection treatments. These chemical disinfectants, which are very effective as regards the oxidation power, the disinfection capability and the bacteriostatic action, produce by-products harmful for human health: Chlorite and Trihalomethanes (THMs) respectively. The Italian Regulations (D.Lgs. 31/2001) sets very restrictive limits for the maximum concentration of these by-products in drinking water. Moreover, from December 2006, the limit for chlorite will be even more restrictive and, with present treatment process, the compliance with the regulation will be very difficult. Therefore the experimentation of alternative treatment techniques and products is of great interest. This article presents an experimental investigation on the combined use of C1O2 and NaC1O in the treatment of final water from two different plants producing drinking water in Florence. The main objective of this investigation was to evaluate the use of these two products in combination so as to keep the advantages (disinfection efficiency and stability in water) and to minimize the disadvantages (by-products formation) present when using this products separately. Positive results achieved in the experimental phase were used to evaluate the possible applications on real drinking water treatment conditions

  5. Self-administration of C1-inhibitor concentrate in patients with hereditary or acquired angioedema caused by C1-inhibitor deficiency

    NARCIS (Netherlands)

    Levi, M; Choi, G; Picavet, C; Hack, CE

    2006-01-01

    Background: Administration of C1-inhibitor concentrate is effective for prophylaxis and treatment of severe angioedema attacks caused by Cl-inhibitor deficiency. The concentrate should be administered intravenously and hence needs to be administered by health care professionals, which might cause co

  6. Hereditary and acquired C1-inhibitor-dependent angioedema: from pathophysiology to treatment.

    Science.gov (United States)

    Zeerleder, Sacha; Levi, Marcel

    2016-06-01

    Uncontrolled generation of bradykinin (BK) due to insufficient levels of protease inhibitors controlling contact phase (CP) activation, increased activity of CP proteins, and/or inadequate degradation of BK into inactive peptides increases vascular permeability via BK-receptor 2 (BKR2) and results in subcutaneous and submucosal edema formation. Hereditary and acquired angioedema due to C1-inhibitor deficiency (C1-INH-HAE and -AAE) are diseases characterized by serious and potentially fatal attacks of subcutaneous and submucosal edemas of upper airways, facial structures, abdomen, and extremities, due to inadequate control of BK generation. A decreased activity of C1-inhibitor is the hallmark of C1-INH-HAE (types 1 and 2) due to a mutation in the C1-inhibitor gene, whereas the deficiency in C1-inhibitor in C1-INH-AAE is the result of autoimmune phenomena. In HAE with normal C1-inhibitor, a significant percentage of patients have an increased activity of factor XIIa due to a FXII mutation (FXII-HAE). Treatment of C1-inhibitor-dependent angioedema focuses on restoring control of BK generation by inhibition of CP proteases by correcting the balance between CP inhibitors and BK breakdown or by inhibition of BK-mediated effects at the BKR2 on endothelial cells. This review will address the pathophysiology, clinical picture, diagnosis and available treatment in C1-inhibitor-dependent angioedema focusing on BK-release and its regulation. Key Messages Inadequate control of bradykinin formation results in the formation of characteristic subcutaneous and submucosal edemas of the skin, upper airways, facial structures, abdomen and extremities as seen in hereditary and acquired C1-inhibitor-dependent angioedema. Diagnosis of hereditary and acquired C1-inhibitor-dependent angioedema may be troublesome as illustrated by the fact that there is a significant delay in diagnosis; a certain grade of suspicion is therefore crucial for quick diagnosis. Submucosal edema formation in

  7. Using the Sub-Game Perfect Nash Equilibrium to Deduce the Effect of Government Subsidy on Consumption Rates and Prices

    Directory of Open Access Journals (Sweden)

    Dr. Magdi Amer

    2015-11-01

    Full Text Available Governments are interested in inducing positive habits and behaviors in its citizens and discouraging ones that are harmful to the individual or to the society. Taxation and legislation are usually used to discourage negative behaviors. Subsidy seems the politically correct way to encourage positive behaviors. In this paper, the Subgame Perfect Nash Equilibrium is used to deduce the effect of the government subsidy on the user consumption, prices and producer and distributor profits.

  8. Oversulfated chondroitin sulfate inhibits the complement classical pathway by potentiating C1 inhibitor.

    Science.gov (United States)

    Zhou, Zhao-Hua; Rajabi, Mohsen; Chen, Trina; Karnaukhova, Elena; Kozlowski, Steven

    2012-01-01

    Oversulfated chondroitin sulfate (OSCS) has become the subject of multidisciplinary investigation as a non-traditional contaminant in the heparin therapeutic preparations that were linked to severe adverse events. In this study, it was found that OSCS inhibited complement fixation on bacteria and bacterial lysis mediated by the complement classical pathway. The inhibition of complement by OSCS is not due to interference with antibody/antigen interaction or due to consumption of C3 associated with FXII-dependent contact system activation. However, OSCS complement inhibition is dependent on C1 inhibitor (C1inh) since the depletion of C1inh from either normal or FXII-deficient complement plasma prevents OSCS inhibition of complement activity. Surface plasmon resonance measurements revealed that immobilized C1inhibitor bound greater than 5-fold more C1s in the presence of OSCS than in presence of heparin. Although heparin can also inhibit complement, OSCS and OSCS contaminated heparin are more potent inhibitors of complement. Furthermore, polysulfated glycosaminoglycan (PSGAG), an anti-inflammatory veterinary medicine with a similar structure to OSCS, also inhibited complement in the plasma of dogs and farm animals. This study provides a new insight that in addition to the FXII-dependent activation of contact system, oversulfated and polysulfated chondroitin-sulfate can inhibit complement activity by potentiating the classical complement pathway regulator C1inh. This effect on C1inh may play a role in inhibiting inflammation as well as impacting bacterial clearance. PMID:23077587

  9. Thyroid hormone transport and metabolism by OATP1C1 and consequences of genetic variation

    DEFF Research Database (Denmark)

    van der Deure, Wendy M; Hansen, Pia Skov; Peeters, Robin P;

    2008-01-01

    OATP1C1 has been characterized as a specific thyroid hormone transporter. Based on its expression in capillaries in different brain regions, OATP1C1 is thought to play a key-role in transporting thyroid hormone across the blood-brain barrier. For this reason, we studied the specificity of...... iodothyronine transport by OATP1C1 in detail by analysis of thyroid hormone uptake in OATP1C1-transfected COS1 cells. Furthermore, we examined whether OATP1C1 is rate-limiting in subsequent thyroid hormone metabolism in cells co-transfected with deiodinases. We also studied the effect of genetic variation in...... the OATP1C1 gene: polymorphisms were determined in 155 blood donors and 1192 Danish twins, and related to serum thyroid hormone levels. In vitro effects of the polymorphisms were analyzed in cells transfected with the variants. Cells transfected with OATP1C1 showed increased transport of T4 and T4...

  10. Oversulfated chondroitin sulfate inhibits the complement classical pathway by potentiating C1 inhibitor.

    Directory of Open Access Journals (Sweden)

    Zhao-Hua Zhou

    Full Text Available Oversulfated chondroitin sulfate (OSCS has become the subject of multidisciplinary investigation as a non-traditional contaminant in the heparin therapeutic preparations that were linked to severe adverse events. In this study, it was found that OSCS inhibited complement fixation on bacteria and bacterial lysis mediated by the complement classical pathway. The inhibition of complement by OSCS is not due to interference with antibody/antigen interaction or due to consumption of C3 associated with FXII-dependent contact system activation. However, OSCS complement inhibition is dependent on C1 inhibitor (C1inh since the depletion of C1inh from either normal or FXII-deficient complement plasma prevents OSCS inhibition of complement activity. Surface plasmon resonance measurements revealed that immobilized C1inhibitor bound greater than 5-fold more C1s in the presence of OSCS than in presence of heparin. Although heparin can also inhibit complement, OSCS and OSCS contaminated heparin are more potent inhibitors of complement. Furthermore, polysulfated glycosaminoglycan (PSGAG, an anti-inflammatory veterinary medicine with a similar structure to OSCS, also inhibited complement in the plasma of dogs and farm animals. This study provides a new insight that in addition to the FXII-dependent activation of contact system, oversulfated and polysulfated chondroitin-sulfate can inhibit complement activity by potentiating the classical complement pathway regulator C1inh. This effect on C1inh may play a role in inhibiting inflammation as well as impacting bacterial clearance.

  11. Trichinella spiralis Paramyosin Binds Human Complement C1q and Inhibits Classical Complement Activation.

    Directory of Open Access Journals (Sweden)

    Ran Sun

    2015-12-01

    Full Text Available Trichinella spiralis expresses paramyosin (Ts-Pmy as a defense mechanism. Ts-Pmy is a functional protein with binding activity to human complement C8 and C9 and thus plays a role in evading the attack of the host's immune system. In the present study, the binding activity of Ts-Pmy to human complement C1q and its ability to inhibit classical complement activation were investigated.The binding of recombinant and natural Ts-Pmy to human C1q were determined by ELISA, Far Western blotting and immunoprecipitation, respectively. Binding of recombinant Ts-Pmy (rTs-Pmy to C1q inhibited C1q binding to IgM and consequently inhibited C3 deposition. The lysis of antibody-sensitized erythrocytes (EAs elicited by the classical complement pathway was also inhibited in the presence of rTs-Pmy. In addition to inhibiting classical complement activation, rTs-Pmy also suppressed C1q binding to THP-1-derived macrophages, thereby reducing C1q-induced macrophages migration.Our results suggest that T. spiralis paramyosin plays an important role in immune evasion by interfering with complement activation through binding to C1q in addition to C8 and C9.

  12. Treatment response after repeated administration of C1 esterase inhibitor for successive acute hereditary angioedema attacks.

    Science.gov (United States)

    Craig, Timothy J; Bewtra, Againdra K; Hurewitz, David; Levy, Robyn; Janss, Gerti; Jacobson, Kraig W; Packer, Flint; Bernstein, Jonathan A; Rojavin, Mikhail A; Machnig, Thomas; Keinecke, Heinz-Otto; Wasserman, Richard L

    2012-01-01

    Placebo-controlled studies established the efficacy of replacement therapy with C1 esterase inhibitor (C1-INH) concentrate for treating single acute hereditary angioedema (HAE) attacks, but only limited data from prospective studies are available on repeated treatment of successive HAE attacks. This study evaluates the association between repeated treatments with 20 U/kg of C1-INH concentrate (Berinert; CSL Behring, Marburg, Germany) for HAE attacks at any body location and treatment response. In a post hoc analysis of an open-label extension study (International Multicenter Prospective Angioedema C1-INH Trial [I.M.P.A.C.T.2]), the association between repeated treatment with C1-INH and times to onset of symptom relief and complete resolution of HAE symptoms was assessed in patients who were treated for at least 15 attacks by linear regression on the ordinal attack number. Eighteen patients received C1-INH concentrate for at least 15 HAE attacks over a mean duration of 34 months. Demographic and baseline characteristics of these patients were similar to those of all patients in the study. The distribution of body locations and the intensity of HAE attacks were similar for each of the first 15 attacks and subsequent attacks. The extent of previous use of C1-INH concentrate had no effect on the time to onset of symptom relief, the time to complete resolution of HAE symptoms, or the time between attacks treated with C1-INH concentrate; the median of individual linear regression coefficients was not statistically significantly different from 0. Treatment with 20 U/kg of C1-INH concentrate provided consistent treatment response in patients treated for multiple successive HAE attacks at any body location. (Clinicaltrials.gov identifier: NCT00292981). PMID:22856636

  13. Atlantoaxial arthrodesis using C1-C2 transarticular screw fixation in a case of Morquio syndrome

    Directory of Open Access Journals (Sweden)

    Arvind G Kulkarni

    2011-01-01

    Full Text Available Prophylactic or therapeutic arthrodesis is recommended for atlantoaxial instability in Morquio syndrome. Occipitocervical fusion, the common approach for upper cervical fusion in Morquio syndrome sacrifices the movements at the occipitoatlantal joints. The use of C1-C2 transarticular screws for achieving C1-C2 arthrodesis, without compromising mobility at the occipitoatlantal joint in Morquio syndrome has not been reported. We report a case of Morquio syndrome with atlantoaxial instability and odontoid hypoplasia, where we successfully achieved C1-C2 arthrodesis using transarticular screws and bone graft. The advantages of this method over other methods of atlantoaxial arthrodesis in Morquio syndrome have also been discussed.

  14. Mutants of complement component C3 cleaved by the C4-specific C1-s protease.

    OpenAIRE

    Mathias, P; Carrillo, C J; Zepf, N E; Cooper, N R; Ogata, R T

    1992-01-01

    To identify some of the structural features determining specific protease recognition of complement components C3 and C4, we used site-specific mutagenesis to construct mutants of murine C3 that are cleaved by the C4-specific C1-s protease. Insertion of three amino acid residues corresponding to residues at the C1-s cleavage site of human C4 into murine C3 at the analogous C3 convertase cleavage site was adequate to render the mutant protein susceptible to C1-s cleavage. In addition, insertio...

  15. Involvement of Helices at the Dimer Interface in ClC-1 Common Gating

    OpenAIRE

    Duffield, Michael; Rychkov, Grigori; Bretag, Allan; Roberts, Michael

    2003-01-01

    ClC-1 is a dimeric, double-pored chloride channel that is present in skeletal muscle. Mutations of this channel can result in the condition myotonia, a muscle disorder involving increased muscle stiffness. It has been shown that the dominant form of myotonia often results from mutations that affect the so-called slow, or common, gating process of the ClC-1 channel. Mutations causing dominant myotonia are seen to cluster at the interface of the ClC-1 channel monomers. This study has investigat...

  16. Modulation of C1-Inhibitor and Plasma Kallikrein Activities by Type IV Collagen

    OpenAIRE

    Sriram Ravindran; Marc Schapira; Patston, Philip A.

    2012-01-01

    The contact system of coagulation can be activated when in contact with biomaterials. As collagen is being tested in novel biomaterials in this study, we have investigated how type IV collagen affects plasma kallikrein and C1-inhibitor. Firstly, we showed C1-inhibitor binds to type IV collagen with a Kd of 0.86 μM. The effects of type IV collagen on plasma kallikrein, factor XIIa, and β-factor XIIa activity and on C1-inhibitor function were determined. Factor XIIa rapidly lost activity in the...

  17. Modulation of C1-Inhibitor and Plasma Kallikrein Activities by Type IV Collagen

    Directory of Open Access Journals (Sweden)

    Sriram Ravindran

    2012-01-01

    Full Text Available The contact system of coagulation can be activated when in contact with biomaterials. As collagen is being tested in novel biomaterials in this study, we have investigated how type IV collagen affects plasma kallikrein and C1-inhibitor. Firstly, we showed C1-inhibitor binds to type IV collagen with a Kd of 0.86 μM. The effects of type IV collagen on plasma kallikrein, factor XIIa, and β-factor XIIa activity and on C1-inhibitor function were determined. Factor XIIa rapidly lost activity in the presence of type IV collagen, whereas plasma kallikrein and β-factor XIIa were more stable. The rate of inhibition of plasma kallikrein by C1-inhibitor was decreased by type IV collagen in a dose-dependent manner. These studies could be relevant to the properties of biomaterials, which contain collagen, and should be considered in the testing for biocompatibility.

  18. Observation of the h_c(1P) using e^+e^- collisions above DDbar threshold

    CERN Document Server

    Pedlar, T K; Hietala, J; Dobbs, S; Metreveli, Z; Seth, K K; Tomaradze, A; Xiao, T; Martin, L; Powell, A; Wilkinson, G; Mendez, H; Ge, J Y; Miller, D H; Shipsey, I P J; Xin, B; Adams, G S; Hu, D; Moziak, B; Napolitano, J; Ecklund, K M; Insler, J; Muramatsu, H; Park, C S; Pearson, L J; Thorndike, E H; Ricciardi, S; Thomas, C; Artuso, M; Blusk, S; Mountain, R; Skwarnicki, T; Stone, S; Zhang, L M; Bonvicini, G; Cinabro, D; Lincoln, A; Smith, M J; Zhou, P; Zhu, J; Naik, P; Rademacker, J; Asner, D M; Edwards, K W; Randrianarivony, K; Tatishvili, G; Briere, R A; Vogel, H; Onyisi, P U E; Rosner, J L; Alexander, J P; Cassel, D G; Das, S; Ehrlich, R; Gibbons, L; Gray, S W; Hartill, D L; Heltsley, B K; Kreinick, D L; Kuznetsov, V E; Patterson, J R; Peterson, D; Riley, D; Ryd, A; Sadoff, A J; Shi, X; Sun, W M; Yelton, J; Rubin, P; Lowrey, N; Mehrabyan, S; Selen, M; Wiss, J; Libby, J; Kornicer, M; Mitchell, R E; Shepherd, M R; Tarbert, C M; Besson, D

    2011-01-01

    Using 586pb^-1 of e^+e^- collision data at Ecm = 4170MeV, produced at the CESR collider and collected with the CLEO-c detector, we observe the process e^+e^- --> pi^+ pi^- h_c(1P) with a significance of greater than 10 sigma. We measure its cross section to be 15.6+-2.3+-1.9+-3.0pb, where the third error is due to the external uncertainty on the branching fraction of psi(2S) --> pi^0 h_c(1P), which we use for normalization. We also find evidence for e^+e^- --> eta h_c(1P) at 4170MeV at the 3 sigma level, and see hints of a rise in the e^+e^- --> pi^+ pi^- h_c(1P) cross section at 4260MeV.

  19. Stereocontrolled Synthesis of the C(1)-C(11) Subunit of the Iejimalides

    DEFF Research Database (Denmark)

    Mendlik, Matthew T.; Cottard, Muriel; Rein, Tobias;

    1997-01-01

    An enantioselective synthesis of the C(1)-C(11) subunit of the iejimalides has been accomplished through a combination of an asymmetric Homer-Wadsworth-Emmons condensation and a chiral pool approach. (C) 1997 Elsevier Science Ltd....

  20. Association of the rs3743205 variant of DYX1C1 with dyslexia in Chinese children

    OpenAIRE

    Waye Mary MY; Chou Crystal HN; Ho Connie SH; Lim Cadmon KP

    2011-01-01

    Abstract Background Dyslexia is a learning disability that is characterized by difficulties in the acquisition of reading and spelling skills independent of intelligence, motivation or schooling. Studies of western populations have suggested that DYX1C1 is a candidate gene for dyslexia. In view of the different languages used in Caucasian and Chinese populations, it is therefore worthwhile to investigate whether there is an association of DYX1C1 in Chinese children with dyslexia. Method and R...

  1. Atlantoaxial arthrodesis using C1-C2 transarticular screw fixation in a case of Morquio syndrome

    OpenAIRE

    Kulkarni, Arvind G; Siddharth M Shah

    2011-01-01

    Prophylactic or therapeutic arthrodesis is recommended for atlantoaxial instability in Morquio syndrome. Occipitocervical fusion, the common approach for upper cervical fusion in Morquio syndrome sacrifices the movements at the occipitoatlantal joints. The use of C1-C2 transarticular screws for achieving C1-C2 arthrodesis, without compromising mobility at the occipitoatlantal joint in Morquio syndrome has not been reported. We report a case of Morquio syndrome with atlantoaxial instability an...

  2. Complement C1q Activates Canonical Wnt Signaling and Promotes Aging-Related Phenotypes

    OpenAIRE

    Atsuhiko T. Naito; Sumida, Tomokazu; Nomura, Seitaro; Liu, Mei-Lan; Higo, Tomoaki; NAKAGAWA, AKITO; Okada, Katsuki; Sakai, Taku; Hashimoto, Akihito; Hara, Yurina; Shimizu, Ippei; Zhu, Weidong; Toko, Haruhiro; Katada, Akemi; Akazawa, Hiroshi

    2012-01-01

    Wnt signaling plays critical roles in development of various organs and pathogenesis of many diseases, and augmented Wnt signaling has recently been implicated in mammalian aging and aging-related phenotypes. We here report that complement C1q activates canonical Wnt signaling and promotes aging-associated decline in tissue regeneration. Serum C1q concentration is increased with aging, and Wnt signaling activity is augmented during aging in the serum and in multiple tissues of wild-type mice,...

  3. Analysis of healthy cohorts for single nucleotide polymorphisms in C1q gene cluster

    Directory of Open Access Journals (Sweden)

    MARIA A. RADANOVA

    2015-12-01

    Full Text Available C1q is the first component of the classical pathway of complement activation. The coding region for C1q is localized on chromosome 1p34.1–36.3. Mutations or single nucleotide polymorphisms (SNPs in C1q gene cluster can cause developing of Systemic lupus erythematosus (SLE because of C1q deficiency or other unknown reason. We selected five SNPs located in 7.121 kbp region on chromosome 1, which were previously associated with SLE and/or low C1q level, but not causing C1q deficiency and analyzed them in terms of allele frequencies and genotype distribution in comparison with Hispanic, Asian, African and other Caucasian cohorts. These SNPs were: rs587585, rs292001, rs172378, rs294179 and rs631090. One hundred eighty five healthy Bulgarian volunteers were genotyped for the selected five C1q SNPs by quantative real-time PCR methods. International HapMap Project has been used for information about genotype distribution and allele frequencies of the five SNPs in, Hispanics, Asians, Africans and others Caucasian cohorts. Bulgarian healthy volunteers and another pooled Caucasian cohort had similar frequencies of genotypes and alleles of rs587585, rs292001, rs294179 and rs631090 SNPs. Nevertheless, genotype AA of rs172378 was significantly overrepresented in Bulgarians when compared to other healthy Caucasians from USA and UK (60% vs 31%. Genotype distribution of rs172378 in Bulgarians was similar to Greek-Cyriot Caucasians. For all Caucasians the major allele of rs172378 was A. This is the first study analyzing the allele frequencies and genotype distribution of C1q gene cluster SNPs in Bulgarian healthy population.

  4. Differential regulation of Aβ42-induced neuronal C1q synthesis and microglial activation

    OpenAIRE

    Tenner Andrea J; Fan Rong

    2005-01-01

    Abstract Expression of C1q, an early component of the classical complement pathway, has been shown to be induced in neurons in hippocampal slices, following accumulation of exogenous Aβ42. Microglial activation was also detected by surface marker expression and cytokine production. To determine whether C1q induction was correlated with intraneuronal Aβ and/or microglial activation, D-(-)-2-amino-5-phosphonovaleric acid (APV, an NMDA receptor antagonist) and glycine-arginine-glycine-aspartic a...

  5. Transcriptional Factor PU.1 Regulates Decidual C1q Expression in Early Pregnancy in Human.

    Science.gov (United States)

    Madhukaran, Shanmuga Priyaa; Kishore, Uday; Jamil, Kaiser; Teo, Boon Heng Dennis; Choolani, Mahesh; Lu, Jinhua

    2015-01-01

    C1q is the first recognition subcomponent of the complement classical pathway, which in addition to being synthesized in the liver, is also expressed by macrophages and dendritic cells (DCs). Trophoblast invasion during early placentation results in accumulation of debris that triggers the complement system. Hence, both early and late components of the classical pathway are widely distributed in the placenta and decidua. In addition, C1q has recently been shown to significantly contribute to feto-maternal tolerance, trophoblast migration, and spiral artery remodeling, although the exact mechanism remains unknown. Pregnancy in mice, genetically deficient in C1q, mirrors symptoms similar to that of human preeclampsia. Thus, regulated complement activation has been proposed as an essential requirement for normal successful pregnancy. Little is known about the molecular pathways that regulate C1q expression in pregnancy. PU.1, an Ets-family transcription factor, is required for the development of hematopoietic myeloid lineage immune cells, and its expression is tissue-specific. Recently, PU.1 has been shown to regulate C1q gene expression in DCs and macrophages. Here, we have examined if PU.1 transcription factor regulates decidual C1q expression. We used immune-histochemical analysis, PCR, and immunostaining to localize and study the gene expression of PU.1 transcription factor in early human decidua. PU.1 was highly expressed at gene and protein level in early human decidual cells including trophoblast and stromal cells. Surprisingly, nuclear as well as cytoplasmic PU.1 expression was observed. Decidual cells with predominantly nuclear PU.1 expression had higher C1q expression. It is likely that nuclear and cytoplasmic PU.1 localization has a role to play in early pregnancy via regulating C1q expression in the decidua during implantation. PMID:25762996

  6. 17 CFR 240.15c1-8 - Sales at the market.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Sales at the market. 240.15c1... Securities Exchange Act of 1934 Rules Relating to Over-The-Counter Markets § 240.15c1-8 Sales at the market... securities exchange that such security is being offered to such customer “at the market” or at a...

  7. C~0 and C~1 theories and test functions for FEM patch test in microstructures

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Among many theories and categories in microstructures,rotation-displacement used as "independent" or "dependent" variables,is a noticeable topic. In FEM,it is called C0 and C1 theory. The convergence criteria of finite elements for microstructures are less mature than those for the conventional thin plate bending problem. In this paper,the patch test functions for assessing convergence of the C0 and C1 finite elements in microstructures is established based on the enhanced patch test theory. The author has further explored the C0 and C1 finite element theories and investigated the difference and correlation between their finite element formulations. Newly proposed finite element theories for microstructures are as follows:(1) the displacement-rotation dependent C1 element that requires the element function satisfying both C0 and C1 continuity;(2) the displacement-rotation independent C0 element which requires new convergence criteria,such as non-zero constant shear stress patch test and zero constant shear stress patch test for approximating C1 element.

  8. Two human homeobox genes, c1 and c8: structure analysis and expression in embryonic development

    International Nuclear Information System (INIS)

    Two human cDNA clones (HHO.c1.95 and HHO.c8.5111) containing a homeobox region have been characterized, and the respective genomic regions have been partially analyzed. Expression of the corresponding genes, termed c1 and c8, was evaluated in different organs and body parts during human embryonic/fetal development. HHO.c1.95 apparently encodes a 217-amino acid protein containing a class I homeodomain that shares 60 out of 61 amino acid residues with the Antennapedia homeodomain of Drosophila melanogaster. HHO.c8.5111 encodes a 153-amino acid protein containing a homeodomains identical to that of the frog AC1 gene. Clones HHO.c1 and HHO.c8 detect by blot-hybridization one and two specific polyadenylylated transcripts, respectively. These are differentially expressed in spinal cord, backbone rudiments, limb buds (or limbs), heart, and skin of human embryos and early fetuses in the 5- to 9-week postfertilization period, thus suggesting that the c1 and c8 genes play a key role in a variety of developmental processes. Together, the results of the embryonic/fetal expression of c1 and c8 and those of two previously analyzed genes (c10 and c13) indicate a coherent pattern of expression of these genes in early human ontogeny

  9. Transcriptional response of four C1q domain containing protein (C1qDC) genes from Venerupis philippinarum exposed to the water soluble fraction of No.0 diesel oil.

    Science.gov (United States)

    Zhang, Linbao; Sun, Wei; Cai, Wengui; Zhang, Zhe; Chen, Haigang; Ma, Shengwei; Jia, Xiaoping

    2016-10-01

    As pattern recognitionreceptors, the C1q-domain-containing (C1qDC) proteins play an important role in the pathogen recognition and complement pathway activation. In the present study, four novel C1q domain containing proteins (designated as VpC1qDC1, VpC1qDC2, VpC1qDC3 and VpC1qDC4) were cloned and characterized from clam Venerupis philippinarum. The four VpC1qDCs all possessed the conserved features critical for the fundamental structure and function of the C1q family. The four VpC1qDCs genes showed differential response profiles after exposure to the water soluble fraction of No.0 diesel oil (WSFD). More notably, VpC1qDC1 and VpC1qDC3 were more sensitive to low concentration of WSFD, as their mRNA level changed by higher magnitudes. In addition, VpC1qDC2 and VpC1qDC4 displayed notable increases with larger amplitude to high concentration of WSFD. All these results suggested that the transcriptional response of VpC1qDCs genes were probably a protective mechanism of the cell to oils pollution. The diverse expression patterns of VpC1qDCs demonstrated that VpC1qDC1 and VpC1qDC3 were sensitive responders to environmental stress in V. philippinarum. PMID:27261881

  10. A type of new conserved quantity deduced from Mei symmetry for Nielsen equations in a holonomic system with unilateral constraints

    Institute of Scientific and Technical Information of China (English)

    Han Yue-Lin; Sun Xian-Ting; Wang Xiao-Xiao; Zhang Mei-Ling; Jia Li-Qun

    2012-01-01

    A type of new conserved quantity deduced from Mei symmetry for Nielsen equations in a holonomic system with unilateral constraints is investigated.Nielsen equations and differential equations of motion for the holonomic mechanical system with unilateral constraints are established.The definition and the criterion of Mei symmetry for Nielsen equations in the holonomic systems with unilateral constraints under the infinitesimal transformations of Lie group are also given.The expressions of the structural equation and a type of new conserved quantity of Mei symmetry for Nielsen equations in the holonomic system with unilateral constraints are obtained.An example is given to illustrate the application of the results.

  11. On the moment of inertia in deformed Ba-Xe nuclei as deduced from gamma-gamma energy correlation experiments

    International Nuclear Information System (INIS)

    The γ-rays following reactions induced by bombarding targets of 114,116,118,120,122Sn with 118 MeV 12C ions were investigated using six NaI(Tl) detectors in a two-dimensional coincidence arrangement. Experimental energy-correlation spectra were extracted from the original coincidence matrices. The energy-correlation spectra exhibit the features expected for rotational nuclei and were used to deduce information on the moment of inertia Isup((2)) = ΔI/Δω. The gross properties of the behaviour of Isup((2)) in the Ba-Xe region are discussed together with their interpretation within the cranked shell model (CSM). (orig.)

  12. Oscillatory electron phonon coupling in Pb/Si(111) deduced by temperature-dependent quantum well states

    Institute of Scientific and Technical Information of China (English)

    Zhang Yan-Feng; Jia Jin-Feng; Han Tie-Zhu; Tang Zhe; Shen Quan-Tong; Guo Yang; Xue Qi-Kun

    2005-01-01

    Photoemission study of atomically flat Pb films with a thickness from 15 to 24 monolayers (ML) have been performed within a temperature range 75-270K. Well-defined quantum well states (QWSs) are observed, which exhibit interesting temperature-dependent behaviours. The peak position of the QWSs shifts towards higher binding energy with increasing substrate temperature, whereas the peak width broadens linearly due to enhanced electron-phonon coupling strength (λ). An oscillatory λ with a period of 2ML is deduced. Preliminary analysis shows that the oscillation can be explained in terms of the interface induced phase variations, and is thus a manifestation of the quantum size effects.

  13. The Janus faces of acquired angioedema: C1-inhibitor deficiency, lymphoproliferation and autoimmunity.

    Science.gov (United States)

    Wu, Maddalena Alessandra; Castelli, Roberto

    2016-02-01

    Several clinical and biological features of lymphoproliferative diseases have been associated with an increased risk of developing autoimmune manifestations. Acquired deficiency of C1-inhibitor (C1-INH) (AAE) is a rare syndrome clinically similar to hereditary angioedema (HAE) characterized by local increase in vascular permeability (angioedema) of the skin and the gastrointestinal and oro-pharyngo-laryngeal mucosa. Bradykinin, a potent vasoactive peptide, released from high molecular weight kininogen when it is cleaved by plasma kallikrein (a serine protease controlled by C1-INH), is the mediator of symptoms. In total 46% of AAE patients carry an underlying hematological disorder including monoclonal gammopathy of uncertain significance (MGUS) or B cell malignancies. However, 74% of AAE patients have anti-C1-INH autoantibodies without hematological, clinical or instrumental evidence of lymphoproliferative disease. Unlike HAE patients, AAE patients usually have late-onset symptoms, do not have a family history of angioedema and present variable response to treatment due to the hypercatabolism of C1-INH. Experiments show that C1-INH and/or the classical complement pathway were consumed by the neoplastic lymphatic tissues and/or anti-C1-INH neutralizing autoantibodies. Therapy of AAE follows two directions: 1) prevention/reversal of the symptoms of angioedema; and 2) treatment of the associated disease. Different forms of B cell disorders coexist and/or evolve into each other in AAE and seem to be dominated by an altered control of B cell proliferation, thus AAE represents an example of the strict link between autoimmunity and lymphoproliferation. PMID:26068904

  14. C1 inhibitor serpin domain structure reveals the likely mechanism of heparin potentiation and conformational disease.

    Science.gov (United States)

    Beinrohr, László; Harmat, Veronika; Dobó, József; Lörincz, Zsolt; Gál, Péter; Závodszky, Péter

    2007-07-20

    C1 inhibitor, a member of the serpin family, is a major down-regulator of inflammatory processes in blood. Genetic deficiency of C1 inhibitor results in hereditary angioedema, a dominantly inheritable, potentially lethal disease. Here we report the first crystal structure of the serpin domain of human C1 inhibitor, representing a previously unreported latent form, which explains functional consequences of several naturally occurring mutations, two of which are discussed in detail. The presented structure displays a novel conformation with a seven-stranded beta-sheet A. The unique conformation of the C-terminal six residues suggests its potential role as a barrier in the active-latent transition. On the basis of surface charge pattern, heparin affinity measurements, and docking of a heparin disaccharide, a heparin binding site is proposed in the contact area of the serpin-proteinase encounter complex. We show how polyanions change the activity of the C1 inhibitor by a novel "sandwich" mechanism, explaining earlier reaction kinetic and mutagenesis studies. These results may help to improve therapeutic C1 inhibitor preparations used in the treatment of hereditary angioedema, organ transplant rejection, and heart attack. PMID:17488724

  15. Caspase cleavage of cytochrome c1 disrupts mitochondrial function and enhances cytochrome c release

    Institute of Scientific and Technical Information of China (English)

    Yushan Zhu; Min Li; Xiaohui Wang; Haijing Jin; Shusen Liu; Jianxin Xu; Quan Chen

    2012-01-01

    Mitochondrial catastrophe can be the cause or consequence of apoptosis and is associated with a number of pathophysiological conditions.The exact relationship between mitochondrial catastrophe and caspase activation is not completely understood.Here we addressed the underlying mechanism,explaining how activated caspase could feedback to attack mitochondria to amplify further cytochrome e (cyto.c) release.We discovered that cytochrome c1 (cyto.c1) in the bc1 complex of the mitochondrial respiration chain was a novel substrate of caspase 3 (casp.3).We found that cyto.c1 was cleaved at the site of D106,which is critical for binding with cyto.c,following apoptotic stresses or targeted expression of casp.3 into tbe mitochondrial intermembrane space.We demonstrated that this cleavage was closely linked with further cyto.c release and mitochondrial catastrophe.These mitochondrial events could be effectively blocked by expressing non-cleavable cyto.c1 (D106A) or by caspase inhibitor z-VAD-fmk.Our results demonstrate that the cleavage of cyto.c1 represents a critical step for the feedback amplification of cyto.c release by caspases and subsequent mitochondrial catastrophe.

  16. Allelic variants of DYX1C1 are not associated with dyslexia in India

    Directory of Open Access Journals (Sweden)

    Saviour Pushpa

    2008-01-01

    Full Text Available Dyslexia is a hereditary neurological disorder that manifests as an unexpected difficulty in learning to read despite adequate intelligence, education, and normal senses. The prevalence of dyslexia ranges from 3 to 15% of the school aged children. Many genetic studies indicated that loci on 6p21.3, 15q15-21, and 18p11.2 have been identified as promising candidate gene regions for dyslexia. Recently, it has been suggested that allelic variants of gene, DYX1C1 influence dyslexia. In the present study, exon 2 and 10 of DYX1C1 has been analyzed to verify whether these single nucleotide polymorphisms (SNPs influence dyslexia, in our population. Our study identified 4 SNPs however, none of these SNPS were found to be significantly associated with dyslexia suggesting DYX1C1 allelic variants are not associated with dyslexia.

  17. Cervicogenic vertigo treated by c1 transverse foramen decompression : a case report.

    Science.gov (United States)

    Park, Junhee; Lee, Chulkyu; You, Namkyu; Kim, Sanghyun; Cho, Kihong

    2014-09-01

    Cervicogenic vertigo was known as Bow hunter's syndrome. Occlusion of vertebral artery causes vertebrobasilar insufficiency and we reported cervicogenic vertigo case which was treated by simple decompression of transverse foramen of C1. The patient was 48 years old female who had left side dominant vertebral artery and vertigo was provoked when she rotated her head to right side. Angiography showed complete obliteration of blood flow of left vertebral artery when her head was rotated to right side. The operation was decompression of left vertebral artery at C1 level. Posterior wall of transverse foramen was resected and vertebral artery was exposed and decompressed. After surgery, vertigo of the patient was disappeared, and angiography showed patent left vertebral artery when her head was rotated to right side. Vertigo caused by compression of cervical vertebral artery could be treated by decompression without fusion or instrumentation, especially in C1 transverse foramen. PMID:25346772

  18. C1q binding and complement activation by prions and amyloids.

    Science.gov (United States)

    Sim, Robert B; Kishore, Uday; Villiers, Christian L; Marche, Patrice N; Mitchell, Daniel A

    2007-01-01

    C1q binds to many non-self and altered-self-materials. These include microorganisms, immune complexes, apoptotic and necrotic cells and their breakdown products, and amyloids. C1q binding to amyloid fibrils found as extracellular deposits in tissues, and subsequent complement activation are involved in the pathology of several amyloid diseases, such as Alzheimer's disease. Prion diseases, such as scrapie also involve formation of amyloid by polymerization of the host prion protein (PrP). Complement activation is likely to contribute to neuronal damage in the end stages of prion diseases, but is also thought to participate in the initial infection, dissemination and replication stages. Infectious prion particles are likely to bind C1q and activate the complement system. Bound complement proteins may then influence the uptake and transport of prion particles by dendritic cells (DCs) and their subsequent proliferation at sites such as follicular DCs. PMID:17544820

  19. Treatment of type I and II hereditary angioedema with Rhucin, a recombinant human C1 inhibitor.

    Science.gov (United States)

    Varga, Lilian; Farkas, Henriette

    2008-11-01

    Hereditary and acquired angioedema are of outstanding clinical importance, as edematous attacks associated with these conditions can thrust afflicted patients into mortal danger. Currently, C1 inhibitor concentrate - a human blood product - is available as a replacement therapy. In view of the limited number of donors, as well as the risk of transmission of blood-borne infections, it is a reasonable expectation to develop a therapeutic alternative based on recombinant technology, which would eliminate all these shortcomings. Pharming (Leiden, The Netherlands) has developed Rhucin, a recombinant human C1 inhibitor, as a proprietary product, which is currently being evaluated in Phase III clinical trials. Ongoing studies conducted within the framework of the development program are almost complete and their interim findings are reassuring. This should facilitate successful regulatory approval in the near future, which is indispensable in order to make Rhucin available for patients with hereditary angioedema or other disorders amenable to C1 inhibitor replacement. PMID:20477114

  20. Identification and Analysis of the Chloroplast rpoC1 Gene Differentially Expressed in Wild Ginseng

    Directory of Open Access Journals (Sweden)

    Lee Kwang-Ho

    2012-06-01

    Full Text Available Panax ginseng is a well-known herbal medicine in traditional Asian medicine, and wild ginseng is widely accepted to be more active than cultivated ginseng in chemoprevention. However, little has actually been reported on the difference between wild ginseng and cultivated ginseng. Thus, to identify and analyze those differences, we used suppressive subtraction hybridization (SSH sequences with microarrays, realtime polymerase chain reaction (PCR, and reverse transcription PCRs (RT-PCRs. One of the clones isolated in this research was the chloroplast rpoC1 gene, a β subunit of RNA polymerase. Real-time RT-PCR results showed that the expression of the rpoC1 gene was significantly upregulated in wild ginseng as compared to cultivated ginseng, so, we conclude that the rpoC1 gene may be one of the important markers of wild ginseng.

  1. Detection of vanC 1 gene transcription in vancomycin-susceptible Enterococcus faecalis

    Directory of Open Access Journals (Sweden)

    Tiane Martin de Moura

    2013-06-01

    Full Text Available Here we report the presence and expression levels of the vanC 1 and vanC 2/3 genes in vancomycin-susceptible strains of Enterococcus faecalis. The vanC 1 and vanC 2/3 genes were located in the plasmid DNA and on the chromosome, respectively. Specific mRNA of the vanC 1 gene was detected in one of these strains. Additionally, analysis of the vanC gene sequences showed that these genes are related to the vanC genes of Enterococcus gallinarum and Enterococcus casseliflavus. The presence of vanC genes is useful for the identification of E. gallinarum and E. casseliflavus. Moreover, this is the first report of vanC mRNA in E. faecalis.

  2. Carbon isotope anomaly in the major plant C1 pool and its global biogeochemical implications

    Directory of Open Access Journals (Sweden)

    J. T. G. Hamilton

    2004-08-01

    Full Text Available We report that the most abundant C1 units of terrestrial plants, the methoxyl groups of pectin and lignin, have a unique carbon isotope signature exceptionally depleted in 13C. Plant-derived C1 volatile organic compounds (VOCs are also anomalously depleted in 13C compared with Cn+1 VOCs. The results confirm that the plant methoxyl pool is the predominant source of biospheric C1 compounds of plant origin such as methanol, chloromethane and bromomethane. Furthermore this pool, comprising ca. 2.5% of carbon in plant biomass, represents an important substrate for methanogenesis and could be a significant source of isotopically light methane entering the atmosphere. Our findings have significant implications for the use of carbon isotope ratios in elucidation of global carbon cycling. Moreover methoxyl groups could act as markers for biological activity in organic matter of terrestrial and extraterrestrial origin.

  3. Carbon isotope anomaly in the major plant C1 pool and its global biogeochemical implications

    Directory of Open Access Journals (Sweden)

    F. Keppler

    2004-01-01

    Full Text Available We report that the most abundant C1 units of terrestrial plants, the methoxyl groups of pectin and lignin, have a unique carbon isotope signature exceptionally depleted in 13C. Plant-derived C1 volatile organic compounds (VOCs are also anomalously depleted in 13C compared with Cn+1 VOCs. The results confirm that the plant methoxyl pool is the predominant source of biospheric C1 compounds of plant origin such as methanol, chloromethane and bromomethane. Furthermore this pool, comprising ca 2.5% of carbon in plant biomass, could be an important substrate for methanogenesis and thus be envisaged as a possible source of isotopically light methane entering the atmosphere. Our findings have significant implications for the use of carbon isotope ratios in elucidation of global carbon cycling. Moreover methoxyl groups could act as markers for biological activity in organic matter of terrestrial and extraterrestrial origin.

  4. Inactivation of factor XII active fragment in normal plasma. Predominant role of C-1-inhibitor.

    Science.gov (United States)

    de Agostini, A; Lijnen, H R; Pixley, R A; Colman, R W; Schapira, M

    1984-06-01

    To define the factors responsible for the inactivation of the active fragment derived from Factor XII (Factor XIIf ) in plasma, we studied the inactivation kinetics of Factor XIIf in various purified and plasma mixtures. We also analyzed the formation of 125I-Factor XIIf -inhibitor complexes by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). In purified systems, the bimolecular rate constants for the reactions of Factor XIIf with C-1-inhibitor, alpha 2-antiplasmin, and antithrombin III were 18.5, 0.91, and 0.32 X 10(4) M-1 min-1, respectively. Furthermore, SDS-PAGE analysis revealed that 1:1 stoichiometric complexes were formed between 125I-Factor XIIf and each of these three inhibitors. In contrast, kinetic and SDS-PAGE studies indicated that Factor XIIf did not react with alpha 1-antitrypsin or alpha 2-macroglobulin. The inactivation rate constant of Factor XIIf by prekallikrein-deficient plasma was 14.4 X 10(-2) min-1, a value that was essentially identical to the value predicted from the studies in purified systems (15.5 X 10(-2) min-1). This constant was reduced to 1.8 X 10(-2) min-1 when Factor XIIf was inactivated by prekallikrein-deficient plasma that had been immunodepleted (less than 5%) of C-1-inhibitor. In addition, after inactivation in normal plasma, 74% of the active 125I-Factor XIIf was found to form a complex with C-1-inhibitor, whereas 26% of the enzyme formed complexes with alpha 2-antiplasmin and antithrombin III. Furthermore, 42% of the labeled enzyme was still complexed with C-1-inhibitor when 125I-Factor XII was inactivated in hereditary angioedema plasma that contained 32% of functional C-1-inhibitor. This study quantitatively demonstrates the dominant role of C-1-inhibitor in the inactivation of Factor XIIf in the plasma milieu. PMID:6725552

  5. Penicillinase plasmid-linked genetic determinants for enterotoxins B and C1 production in Staphylococcus aureus.

    OpenAIRE

    Altboum, Z; Hertman, I; Sarid, S

    1985-01-01

    The genes encoding for beta-lactamase (bla+) and resistance to metallic ions (cadmium, mercury, lead, arsenate, and arsenite) were located in a 56.2-kilobase plasmid, pZA10, isolated from a clinical strain, Staphylococcus aureus 6344. This strain produced enterotoxin B and enterotoxin C1. Elimination of pZA10 by either sodium dodecyl sulfate or heat treatment (43 degrees C) resulted in the loss of the capability of the bacteria to produce both enterotoxin B and enterotoxin C1. A physical map ...

  6. Meningococcal PorA/C1, a channel that combines high conductance and high selectivity.

    OpenAIRE

    Song, J.; Minetti, C A; Blake, M. S.; Colombini, M

    1999-01-01

    Class 1 porins (PorA/C1) from Neisseria meningitidis achieve both high selectivity and high conductance. The channel is highly selective (24:1 Na+ over Cl-), suggesting a highly negatively charged selectivity filter. The trimeric nature of PorA/C1 accounts for part of the enormous conductance in 200 mM NaCl (0.97nS). However, the currents that can be achieved exceed the simple infinite-sink calculation for a pore 0.7 nm in radius (estimated from nonelectrolyte permeability). The conductance i...

  7. The C1q Family of Proteins: Insights into the Emerging Non-Traditional Functions

    OpenAIRE

    Ghebrehiwet, Berhane; Hosszu, Kinga K.; Valentino, Alisa; Peerschke, Ellinor I. B.

    2012-01-01

    Research conducted over the past 20 years have helped us unravel not only the hidden structural and functional subtleties of human C1q, but also has catapulted the molecule from a mere recognition unit of the classical pathway to a well-recognized molecular sensor of damage-modified self or non-self antigens. Thus, C1q is involved in a rapidly expanding list of pathological disorders – including autoimmunity, trophoblast migration, preeclampsia, and cancer. The results of two recent reports a...

  8. C1-esterase inhibitor blocks T lymphocyte proliferation and cytotoxic T lymphocyte generation in vitro

    DEFF Research Database (Denmark)

    Nissen, Mogens Holst; Bregenholt, S; Nording, J A;

    1998-01-01

    beta2m in nanomolar amounts to a one-way allogenic mixed lymphocyte culture (MLC) increased the endogenous production of IL-2 and the generation of allo-specific cytotoxic T lymphocytes. C1-inh was purified from fresh human plasma and added to human or murine MLC and mitogen-stimulated lymphocyte...... cultures grown in the presence of complement-inactivated serum. Read-outs were cell proliferation, lymphokine production and development of T cell-mediated cytotoxicity. We found that addition of C1-inh to MLC and mitogen-exposed murine and human lymphocyte cultures inhibited proliferation, the development...

  9. Diagnosis and treatment of hereditary angioedema with normal C1 inhibitor

    Directory of Open Access Journals (Sweden)

    Bork Konrad

    2010-07-01

    Full Text Available Abstract Until recently it was assumed that hereditary angioedema is a disease that results exclusively from a genetic deficiency of the C1 inhibitor. In 2000, families with hereditary angioedema, normal C1 inhibitor activity and protein in plasma were described. Since then numerous patients and families with that condition have been reported. Most of the patients by far were women. In many of the affected women, oral contraceptives, hormone replacement therapy containing estrogens, and pregnancies triggered the clinical symptoms. Recently, in some families mutations in the coagulation factor XII (Hageman factor gene were detected in the affected persons.

  10. Role of human heterogeneous nuclear ribonucleoprotein C1/C2 in dengue virus replication

    OpenAIRE

    Dechtawewat, Thanyaporn; Songprakhon, Pucharee; Limjindaporn, Thawornchai; Puttikhunt, Chunya; Kasinrerk, Watchara; Saitornuang, Sawanan; Yenchitsomanus, Pa-Thai; Noisakran, Sansanee

    2015-01-01

    Background Host and viral proteins are involved in dengue virus (DENV) replication. Heterogeneous ribonucleoprotein (hnRNP) C1/C2 are abundant host cellular proteins that exhibit RNA binding activity and play important roles in the replication of positive-strand RNA viruses such as poliovirus and hepatitis C virus. hnRNP C1/C2 have previously been shown to interact with vimentin and viral NS1 in DENV-infected cells; however, their functional role in DENV replication is not clearly understood....

  11. C1 esterase inhibitor deficiency in X-linked hypogammaglobulinaemia: an anomaly fostering anaphylactoid reactions following intramuscular gammaglobulin administration.

    OpenAIRE

    Pollack, S; Cunningham-Rundles, C; Good, R A; Day, N K

    1986-01-01

    A patient with apparent X-linked agammaglobulinaemia was found to be inordinately susceptible to anaphylactoid reactions to intramuscular injections of gammaglobulin. The patient was found also to have low levels of C1 esterase inhibitor (C1 INH). The possibility that the C1 INH deficiency and in this patient, whether genetic or acquired, fostered the susceptibility to the production of anaphylactoid reactions after gammaglobulin injections urges further studies of the association of C1 INH d...

  12. C 1 natural element method for strain gradient linear elasticity and its application to microstructures

    Science.gov (United States)

    Nie, Zhi-Feng; Zhou, Shen-Jie; Han, Ru-Jun; Xiao, Lin-Jing; Wang, Kai

    2012-02-01

    C 1 natural element method ( C 1 NEM) is applied to strain gradient linear elasticity, and size effects on microstructures are analyzed. The shape functions in C 1 NEM are built upon the natural neighbor interpolation (NNI), with interpolation realized to nodal function and nodal gradient values, so that the essential boundary conditions (EBCs) can be imposed directly in a Galerkin scheme for partial differential equations (PDEs). In the present paper, C 1 NEM for strain gradient linear elasticity is constructed, and several typical examples which have analytical solutions are presented to illustrate the effectiveness of the constructed method. In its application to microstructures, the size effects of bending stiffness and stress concentration factor (SCF) are studied for microspeciem and microgripper, respectively. It is observed that the size effects become rather strong when the width of spring for microgripper, the radius of circular perforation and the long axis of elliptical perforation for microspeciem come close to the material characteristic length scales. For the U-shaped notch, the size effects decline obviously with increasing notch radius, and decline mildly with increasing length of notch.

  13. C1 natural element method for strain gradient linear elasticity and its application to microstructures

    Institute of Scientific and Technical Information of China (English)

    Zhi-Feng Nie; Shen-Jie Zhou; Ru-Jun Han; Lin-Jing Xiao; Kai Wang

    2012-01-01

    C1 natural element method (C1 NEM) is applied to strain gradient linear elasticity,and size effects on microstructures are analyzed.The shape functions in C1 NEM are built upon the natural neighbor interpolation (NNI),with interpolation realized to nodal function and nodal gradient values,so that the essential boundary conditions (EBCs) can be imposed directly in a Galerkin scheme for partial differential equations (PDEs).In the present paper,C1 NEM for strain gradient linear elasticity is constructed,and several typical examples which have analytical solutions are presented to illustrate the effectiveness of the constructed method.In its application to microstructures,the size effects of bending stiffness and stress concentration factor (SCF) are studied for microspeciem and microgripper,respectively.It is observed that the size effects become rather strong when the width of spring for microgripper,the radius of circular perforation and the long axis of elliptical perforation for microspeciem come close to the material characteristic length scales.For the U-shaped notch,the size effects decline obviously with increasing notch radius,and decline mildly with increasing length of notch.

  14. Reactor pressure vessel steels ASME SA533B and SA508 C1.2

    International Nuclear Information System (INIS)

    The report presents the results of the microstructural studies of steels SA533B and SA508 C1.2 obtained in connection with a programme initiated to gather and create information needed for the assessment of structural integrity of the reactor pressure vessels. The as-quenched and variably tempered microstructures were studied with optical, scanning and transmission electron microscopes. (author)

  15. Cleanup Verification Package for the 118-C-1, 105-C Solid Waste Burial Ground

    Energy Technology Data Exchange (ETDEWEB)

    M. J. Appel and J. M. Capron

    2007-07-25

    This cleanup verification package documents completion of remedial action for the 118-C-1, 105-C Solid Waste Burial Ground. This waste site was the primary burial ground for general wastes from the operation of the 105-C Reactor and received process tubes, aluminum fuel spacers, control rods, reactor hardware, spent nuclear fuel and soft wastes.

  16. Toward the Total Synthesis of Scleritodermin A: Preparation of the C1-N15 Fragment

    OpenAIRE

    Sellanes, Diver; Manta, Eduardo; Serra, Gloria

    2007-01-01

    The synthesis of the C1-N15 fragment of the marine natural product Scleritodermin A has been accomplished through a short and stereocontrolled sequence. Highlights of this route include the synthesis of the novel ACT fragment and the formation of the α-keto amide linkage by the use of a highly activated α, β-ketonitrile.

  17. Known results and open problems on C1 linearization in Banach spaces

    OpenAIRE

    Munhoz Rodrigues, Hildebrando; Solà-Morales Rubió, Joan

    2012-01-01

    The purpose of this paper is to review the results obtained by the authors on linearization of dynamical systems in infinite dimen- sional Banach spaces, especially in the C 1 case, and also to present some open problems that we believe that are still important for the understanding of the theory.

  18. $\\chi_{c1}$ and $\\chi_{c2}$ production at $e^+e^-$ colliders

    CERN Document Server

    Czyz, Henryk; Tracz, Szymon

    2016-01-01

    Direct, resonant production of the charmonium states $\\chi_{c1}$ and $\\chi_{c2}$ in electron-positron annihilation is investigated. Depending on details of the model, a sizeable variation of the prediction for the production cross section is anticipated. It is demonstrated that resonant production could be observed under favorable circumstances.

  19. Percolation on strings and the cover-up of the c=1 disaster

    International Nuclear Information System (INIS)

    We study percolation on the worldsheets of string theory for c=0, 1/2, 1 and 2. For c1. It thus appears likely that simulations for c=2, 3 .. on numerically accessible lattices will fail to capture even the qualitative behavior of the continuum limit. (orig.)

  20. 26 CFR 31.3302(c)-1 - Limit on total credits.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 15 2010-04-01 2010-04-01 false Limit on total credits. 31.3302(c)-1 Section 31... credits. (a) In general. Paragraph (b) of this section relates to the limitation on the aggregate of the credits allowable under section 3302 (a) and (b). Paragraph (c) of this section relates to...

  1. In vivo 13 carbon metabolic imaging at 3T with hyperpolarized 13C-1-pyruvate.

    Science.gov (United States)

    Kohler, S J; Yen, Y; Wolber, J; Chen, A P; Albers, M J; Bok, R; Zhang, V; Tropp, J; Nelson, S; Vigneron, D B; Kurhanewicz, J; Hurd, R E

    2007-07-01

    We present for the first time dynamic spectra and spectroscopic images acquired in normal rats at 3T following the injection of (13)C-1-pyruvate that was hyperpolarized by the dynamic nuclear polarization (DNP) method. Spectroscopic sampling was optimized for signal-to-noise ratio (SNR) and for spectral resolution of (13)C-1-pyruvate and its metabolic products (13)C-1-alanine, (13)C-1-lactate, and (13)C-bicarbonate. Dynamic spectra in rats were collected with a temporal resolution of 3 s from a 90-mm axial slab using a dual (1)H-(13)C quadrature birdcage coil to observe the combined effects of metabolism, flow, and T(1) relaxation. In separate experiments, spectroscopic imaging data were obtained during a 17-s acquisition of a 20-mm axial slice centered on the rat kidney region to provide information on the spatial distribution of the metabolites. Conversion of pyruvate to lactate, alanine, and bicarbonate occurred within a minute of injection. Alanine was observed primarily in skeletal muscle and liver, while pyruvate, lactate, and bicarbonate concentrations were relatively high in the vasculature and kidneys. In contrast to earlier work at 1.5 T, bicarbonate was routinely observed in skeletal muscle as well as the kidney and vasculature. PMID:17659629

  2. C1-C2 rotary subluxation following posterior stabilization for congenital atlantoaxial dislocation.

    Directory of Open Access Journals (Sweden)

    Behari S

    2000-04-01

    Full Text Available The authors report a rare complication of C1-C2 rotary subluxation in two children following posterior stabilization for congenital atlantoaxial dislocation (AAD. A patient, with mobile AAD, underwent Brook′s C1-C2 fusion while the other, with fixed AAD, underwent transoral decompression followed by Jain′s occipitocervical fusion. A pre-existing ligamentous laxity associated with an asymmetrical wire tightening or slippage of the wires due to rotation of the neck in the former, and the drilling of the C1-C2 lateral joints during the transoral procedure in the latter, could have contributed to the rotary subluxation. Both patients presented with persistent torticollis due to fusion in an asymmetrical position with dislocated facet joints. Rotary C1-C2 subluxation, when coexisting with anterior dislocation, has the potential to cause severe and occasionally fatal cord compression. Well defined criteria to diagnose this entity by conventional radiology exist, however, due to the overlap of anatomy, the condition is often overlooked. In the present study, three dimensional reconstruction images using helical computerized tomography were very useful in delineating the subluxation and in planning its surgical reduction and arthrodesis.

  3. Cleanup Verification Package for the 118-C-1, 105-C Solid Waste Burial Ground

    International Nuclear Information System (INIS)

    This cleanup verification package documents completion of remedial action for the 118-C-1, 105-C Solid Waste Burial Ground. This waste site was the primary burial ground for general wastes from the operation of the 105-C Reactor and received process tubes, aluminum fuel spacers, control rods, reactor hardware, spent nuclear fuel and soft wastes

  4. Stereoselective synthesis of the C1–C13 segment of dolabelide B

    OpenAIRE

    Keck, Gary E.; McLaws, Mark D.

    2005-01-01

    The efficient construction of the C1–C13 segment of dolabelide B is described. A key element of the synthesis entails BITIP catalyzed asymmetric methallylation to establish the C7 stereocenter, which was then used to direct the stereoselective installation of the C9 and C11 centers through Evans reduction and 1,5-anti aldol condensation, respectively.

  5. Heterogeneous nuclear ribonucleoproteins C1/C2 identified as autoantigens by biochemical and mass spectrometric methods

    DEFF Research Database (Denmark)

    Heegaard, N H; Larsen, Martin Røssel; Muncrief, T;

    2000-01-01

    gel and their contents were analyzed by matrix-assisted laser desorption-ionization (MALDI) or nanoelectrospray ionization time-of-flight (TOF) tandem mass spectrometry (MS) after in-gel digestion with trypsin. A database search identified the proteins as the C1 and C2 heterogeneous nuclear...

  6. 17 CFR 240.15c1-2 - Fraud and misrepresentation.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Fraud and misrepresentation... Securities Exchange Act of 1934 Rules Relating to Over-The-Counter Markets § 240.15c1-2 Fraud and... any act, practice, or course of business which operates or would operate as a fraud or deceit upon...

  7. 26 CFR 301.6230(c)-1 - Claim arising out of erroneous computation, etc.

    Science.gov (United States)

    2010-04-01

    ... contained in 26 CFR part 1, revised April 1, 2001. ... 26 Internal Revenue 18 2010-04-01 2010-04-01 false Claim arising out of erroneous computation, etc....6230(c)-1 Claim arising out of erroneous computation, etc. (a) In general. A claim for refund...

  8. 12 CFR 563c.1 - Form and content of financial statements.

    Science.gov (United States)

    2010-01-01

    ... ACCOUNTING REQUIREMENTS Form and Content of Financial Statements § 563c.1 Form and content of financial... statements shall: (1) Be prepared and presented in accordance with generally accepted accounting principles... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Form and content of financial statements....

  9. Mutational spectrum and phenotypes in Danish families with hereditary angioedema because of C1 inhibitor deficiency

    DEFF Research Database (Denmark)

    Bygum, A; Fagerberg, C R; Ponard, D; Monnier, N; Lunardi, J; Drouet, C

    2011-01-01

    Hereditary angioedema (HAE), type I and II, is an autosomal dominant disease with deficiency of functional C1 inhibitor protein causing episodic swellings of skin, mucosa and viscera. HAE is a genetically heterogeneous disease with more than 200 different mutations in the SERPING1 gene. A genotype...

  10. Rhucin, a recombinant C1 inhibitor for the treatment of hereditary angioedema and cerebral ischemia.

    Science.gov (United States)

    Longhurst, Hilary

    2008-03-01

    Pharming NV and Esteve are developing Rhucin, a recombinant human C1 esterase inhibitor. Rhucin is currently undergoing phase III clinical trials in North America and is awaiting regulatory approval in Western Europe for the treatment of prophylactic and acute hereditary angioedema. Pharming is also investigating Rhucin for the potential treatment of cerebral ischemic injury. PMID:18311668

  11. A South American Prehistoric Mitogenome: Context, Continuity, and the Origin of Haplogroup C1d.

    Science.gov (United States)

    Sans, Mónica; Figueiro, Gonzalo; Hughes, Cris E; Lindo, John; Hidalgo, Pedro C; Malhi, Ripan S

    2015-01-01

    Based on mitochondrial DNA (mtDNA), it has been estimated that at least 15 founder haplogroups peopled the Americas. Subhaplogroup C1d3 was defined based on the mitogenome of a living individual from Uruguay that carried a lineage previously identified in hypervariable region I sequences from ancient and modern Uruguayan individuals. When complete mitogenomes were studied, additional substitutions were found in the coding region of the mitochondrial genome. Using a complete ancient mitogenome and three modern mitogenomes, we aim to clarify the ancestral state of subhaplogroup C1d3 and to better understand the peopling of the region of the Río de la Plata basin, as well as of the builders of the mounds from which the ancient individuals were recovered. The ancient mitogenome, belonging to a female dated to 1,610±46 years before present, was identical to the mitogenome of one of the modern individuals. All individuals share the mutations defining subhaplogroup C1d3. We estimated an age of 8,974 (5,748-12,261) years for the most recent common ancestor of C1d3, in agreement with the initial peopling of the geographic region. No individuals belonging to the defined lineage were found outside of Uruguay, which raises questions regarding the mobility of the prehistoric inhabitants of the country. Moreover, the present study shows the continuity of Native lineages over at least 6,000 years. PMID:26509686

  12. 26 CFR 25.2523(c)-1 - Interest in unidentified assets.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 14 2010-04-01 2010-04-01 false Interest in unidentified assets. 25.2523(c)-1... unidentified assets. (a) Section 2523(c) provides that if an interest passing to a donee spouse may be satisfied out of a group of assets (or their proceeds) which include a particular asset that would be...

  13. ${H}^{1}\\cap {L}^{p}$ versus ${C}^{1}$ Local Minimizers

    OpenAIRE

    Zhong, Yansheng

    2014-01-01

    We show that a local minimizer of $\\mathrm{\\Phi }$ in the ${C}^{1}$ topology must be a local minimizer in the ${H}^{1}\\cap {L}^{p}$ topology, under suitable assumptions for the functional $\\Phi =(1/2){{\\int }_{\\Omega}|\

  14. Spirastrellolide E: Synthesis of an advanced C(1)-C(24) southern hemisphere

    Science.gov (United States)

    Sokolsky, Alexander; Wang, Xiaozhao; Smith, Amos B.

    2014-01-01

    The synthesis of a C(1)-C(24) advanced southern hemisphere fragment towards the total synthesis of spirastrellolide E has been achieved. Highlights of the route include a highly convergent Type I Anion Relay Chemistry (ARC) tactic for fragment assembly, in conjunction with a directed, regioselective gold-catalyzed alkyne functionalization to generate the central unsaturated [6,6]-spiroketal. PMID:26097261

  15. Association of the rs3743205 variant of DYX1C1 with dyslexia in Chinese children

    Directory of Open Access Journals (Sweden)

    Waye Mary MY

    2011-05-01

    Full Text Available Abstract Background Dyslexia is a learning disability that is characterized by difficulties in the acquisition of reading and spelling skills independent of intelligence, motivation or schooling. Studies of western populations have suggested that DYX1C1 is a candidate gene for dyslexia. In view of the different languages used in Caucasian and Chinese populations, it is therefore worthwhile to investigate whether there is an association of DYX1C1 in Chinese children with dyslexia. Method and Results Eight single nucleotide polymorphisms (SNPs were genotyped from three hundred and ninety three individuals from 131 Chinese families with two which have been reported in the literature and six tag SNPs at DYX1C1. Analysis for allelic and haplotypic associations was performed with the UNPHASED program and multiple testing was corrected using false discovery rates. We replicated the previously reported association of rs3743205 in Chinese children with dyslexia (pcorrected = 0.0072. This SNP was also associated with rapid naming, phonological memory and orthographic skills in quantitative trait analysis. Conclusion Our findings suggest that DYX1C1 is associated with dyslexia in people of Chinese ethnicity in Hong Kong.

  16. A simple method for the preparation and purification of C1 complement cleaved beta 2-microglobulin from human serum

    DEFF Research Database (Denmark)

    Nissen, Mogens Holst; Johansen, B; Bjerrum, Ole Jannik

    1997-01-01

    A simple method is described for the preparation of proteolytically processed forms of beta 2-microglobulin suitable for structural and biological studies. PEG 6000 was added to the serum of healthy individuals to precipitate the C1 complement complex from C1 esterase inhibitor (C1-inh). After di...... component was seen by SDS-PAGE stained with Coomassie Brilliant Blue....

  17. 17 CFR 230.160 - Registered investment company exemption from Section 101(c)(1) of the Electronic Signatures in...

    Science.gov (United States)

    2010-04-01

    ... exemption from Section 101(c)(1) of the Electronic Signatures in Global and National Commerce Act. 230.160...(c)(1) of the Electronic Signatures in Global and National Commerce Act. A prospectus for an... 101(c)(1) of the Electronic Signatures in Global and National Commerce Act....

  18. 40 CFR 721.10108 - Naphthalenedisulfonic acid, hydrozy-[[[(hydroxyl-disulfo-naphthaleneyl)azo]-alkyl(C=1-5...

    Science.gov (United States)

    2010-07-01

    ...- -alkyl(C=1-5)-(sulfoalkoxy)cyclic]azo]-substituted azo-, metal salt (generic). 721.10108 Section 721... Naphthalenedisulfonic acid, hydrozy- -alkyl(C=1-5)-(sulfoalkoxy)cyclic]azo]-substituted azo-, metal salt (generic). (a... generically as naphthalenedisulfonic acid, hydrozy- -alkyl(C=1-5)-(sulfoalkoxy)cyclic]azo]-substituted...

  19. Photo-electrochemical Oxidation of Organic C1 Molecules over WO3 Films in Aqueous Electrolyte: Competition Between Water Oxidation and C1 Oxidation.

    Science.gov (United States)

    Reichert, Robert; Zambrzycki, Christian; Jusys, Zenonas; Behm, R Jürgen

    2015-11-01

    To better understand organic-molecule-assisted photo-electrochemical water splitting, photo-electrochemistry and on-line mass spectrometry measurements are used to investigate the photo-electrochemical oxidation of the C1 molecules methanol, formaldehyde, and formic acid over WO3 film anodes in aqueous solution and its competition with O2 evolution from water oxidation O2 (+) and CO2 (+) ion currents show that water oxidation is strongly suppressed by the organic species. Photo-electro-oxidation of formic acid is dominated by formation of CO2 , whereas incomplete oxidation of formaldehyde and methanol prevails, with the selectivity for CO2 formation increasing with increasing potential and light intensity. The mechanistic implications for the photo-electro-oxidation of the organic molecules and its competition with water oxidation, which could be derived from this novel approach, are discussed. PMID:26382643

  20. The level of non-thermal velocity fluctuations deduced from Doppler spectroscopy and its role on TJ-II confinement

    CERN Document Server

    Zurro, B

    2009-01-01

    The goal of this investigation is to study, in the line of previous works, the level of velocity fluctuations in different scenarios of the TJ-II stellarator. The method followed consists in measuring the apparent Doppler temperature of C4+ and protons with high spectral resolution techniques with spatial resolution. The level of turbulent velocities in the plasma has been deduced from the difference observed between the apparent temperature of both species, following a method previously presented and borrowed from astrophysics. The study of this difference, as a function of plasma density and injected power, provides a way to explore if this turbulence plays any role in the confinement of the hot TJ-II plasma.

  1. Deduced soft-rotator model Hamiltonian parameters and collective properties of medium-to-heavy even-even nuclei

    International Nuclear Information System (INIS)

    The soft-rotator model Hamiltonian parameters were deduced for 63 even-even medium and heavy nuclei in a mass range 56 ≤ A ≤ 238. We obtained those values by the combination of the low-lying level structure and the coupled-channels proton scattering analyses. It was found that the values of the effective quadrupole and octupole deformations obtained were consistent with those derived from experimental data. Besides, the equilibrium ground-state quadrupole deformation parameters were also in reasonable accord with the theoretical mass-models results for deformed heavy nuclei. In this report, we present a complete set of the Hamiltonian parameters for each nucleus. The obtained values of the parameters often varied with the constituent neutron and/or proton numbers anomalously. On the other hand, some clear systematic trends were seen among the major Hamiltonian parameters. (author)

  2. Problems of impurities deducing from multicomponent media at thermal heating, ionization and rotation of plasma in crossed fields

    International Nuclear Information System (INIS)

    The possibility of multicomponent mixtures separation at thermal heating, ionization and plasma rotation in relation to the spent nuclear fuel (SNF) is shown. At thermal heating it is possible to allocate up to 75% of impurities of fission products (FP), after which the SNF contains oxides of zirconium, niobium and lanthanides. At the stage of ionization it is impossible to deduce the lanthanide oxides, but it is possible to remove partially the oxides of zirconium and niobium. Further removal of impurities will occur in rotated plasma. Under certain conditions heavy ions will get to lateral surface of vacuum chamber, and the light ones will move along the magnetic field lines and precipitate on the collector. The molecular plasma has energy cost to excitation of vibrational and rotational degrees of freedom, dissociation. As simulation media it is advisable to use non-radioactive isotopes of spent nuclear fuel oxides

  3. Structural and functional characterization of hBD-1(Ser35), a peptide deduced from a DEFB1 polymorphism.

    Science.gov (United States)

    Circo, Raffaella; Skerlavaj, Barbara; Gennaro, Renato; Amoroso, Antonio; Zanetti, Margherita

    2002-04-26

    beta-Defensins are mammalian antimicrobial peptides that share a unique disulfide-bonding motif of six conserved cysteines. An intragenic polymorphism of the DEFB1 gene that changes a highly conserved Cys to Ser in the peptide coding region has recently been described. The deduced peptide cannot form three disulfide bonds, as one of the cysteines is unpaired. We have determined the cysteine connectivities of a corresponding synthetic hBD-1(Ser35) peptide, investigated the structure by circular dichroism spectroscopy, and assayed the in vitro antimicrobial activity. Despite a different arrangement of the disulfides, hBD-1(Ser35) proved as active as hBD-1 against the microorganisms tested. This activity likely depends on the ability of hBD-1(Ser35) to adopt an amphipathic conformation in hydrophobic environment, similar to the wild type peptide, as suggested by CD spectroscopy. PMID:12054642

  4. On the $\\lambda$ energy dependence deduced from BEC of $\\pi\\pi$ pairs produced in $pp$ collisions

    CERN Document Server

    Alexander, G

    2016-01-01

    The $\\sqrt{s_{pp}}$ behavior of the chaoticity parameter $\\lambda$, derived from Bose - Einstein Correlations (BEC) of pion-pairs produced in $pp$ collisions, is investigated. Considered are the one and three dimensions (1D, 3D) of the BEC analyzed in terms of a Gaussian and/or Exponential distributions. A marked difference is observed between the $\\lambda$ dependence on energy in the 1D and the 3D analyzes. The experimental data are examined in terms of the relation between the pion cluster of sources and the BEC dimension R which in turn are deduced from the charged outgoing particle multiplicity. While in this approach the general decrease with energy of the 1D $\\lambda$ is accounted for it fails to represent the few 3D $\\lambda$ data which are seen to remain constant with energy above $\\sim$200 GeV.

  5. Use of activity measurements in the plume from Chernobyl to deduce fuel state before, during and after the accident

    International Nuclear Information System (INIS)

    Work performed at Berkely Nuclear Laboratories both prior to the meeting in Vienna at which USSR gave full details of the Chernobyl accident and after that meeting is recorded. Plume data from Western Europe were used to deduce the likely damage to the fuel and its previous irradiation history. The note concludes that the source to the environment consisted of an initial dispersion of fuel particulate followed by a prolonged release at a lower rate, the total release being some 3% of the core inventory of fuel. Early and late in the release period it was enhanced in volatile species. Damage to the fuel was thus due both to mechanical disruption and to high temperatures. During the early dispersive event high temperatures (probably approaching fuel melting) were reached in some of the core, though the proportion of the fuel affected may have been small. (UK)

  6. Solution conformation and dynamics of a tetrasaccharide related to the LewisX antigen deduced by NMR relaxation measurements

    International Nuclear Information System (INIS)

    1H-NMR cross-relaxation rates and nonselective longitudinal relaxation times have been obtained at two magnetic fields (7.0 and 11.8 T) and at a variety of temperatures for the branched tetrasaccharide methyl 3-O-α-N-acetyl-galactosaminyl-β-galactopyranosyl-(1→4)[3-O-α-fucosyl] -glucopyranoside (1), an inhibitor of astrocyte growth. In addition, 13C-NMR relaxation data have also been recorded at both fields. The 1H-NMR relaxation data have been interpreted using different motional models to obtain proton-proton correlation times. The results indicate that the GalNAc and Fuc rings display more extensive local motion than the two inner Glc and Gal moieties, since those present significantly shorter local correlation times. The13C-NMR relaxation parameters have been interpreted in terms of the Lipari-Szabo model-free approach. Thus, order parameters and internal motion correlation times have been deduced. As obtained for the1H-NMR relaxation data, the two outer residues possess smaller order parameters than the two inner rings. Internal correlation times are in the order of 100 ps. The hydroxymethyl groups have also different behaviour,with the exocyclic carbon on the glucopyranoside unit showing the highestS2. Molecular dynamics simulations using a solvated system have also been performed and internal motion correlation functions have been deduced from these calculations. Order parameters and interproton distances have been compared to those inferred from the NMR measurements. The obtained results are in fair agreement with the experimental data

  7. Solution conformation and dynamics of a tetrasaccharide related to the Lewis{sup X} antigen deduced by NMR relaxation measurements

    Energy Technology Data Exchange (ETDEWEB)

    Poveda, Ana [Universidad Autonoma de Madrid, Servicio Interdepartamental de Investigacion (Spain); Asensio, Juan Luis; Martin-Pastor, Manuel; Jimenez-Barbero, Jesus [Instituto de Quimica Organica, CSIC, Grupo de Carbohidratos (Spain)

    1997-07-15

    {sup 1}H-NMR cross-relaxation rates and nonselective longitudinal relaxation times have been obtained at two magnetic fields (7.0 and 11.8 T) and at a variety of temperatures for the branched tetrasaccharide methyl 3-O-{alpha}-N-acetyl-galactosaminyl-{beta}-galactopyranosyl-(1{sup {yields}}4)[3-O-{alpha}-fucosyl] -glucopyranoside (1), an inhibitor of astrocyte growth. In addition, {sup 13}C-NMR relaxation data have also been recorded at both fields. The {sup 1}H-NMR relaxation data have been interpreted using different motional models to obtain proton-proton correlation times. The results indicate that the GalNAc and Fuc rings display more extensive local motion than the two inner Glc and Gal moieties, since those present significantly shorter local correlation times. The{sup 13}C-NMR relaxation parameters have been interpreted in terms of the Lipari-Szabo model-free approach. Thus, order parameters and internal motion correlation times have been deduced. As obtained for the{sup 1}H-NMR relaxation data, the two outer residues possess smaller order parameters than the two inner rings. Internal correlation times are in the order of 100 ps. The hydroxymethyl groups have also different behaviour,with the exocyclic carbon on the glucopyranoside unit showing the highestS{sup 2}. Molecular dynamics simulations using a solvated system have also been performed and internal motion correlation functions have been deduced from these calculations. Order parameters and interproton distances have been compared to those inferred from the NMR measurements. The obtained results are in fair agreement with the experimental data.

  8. Complement component C1r mediated cleavage of the heavy chain of the major histocompatibility class I antigens

    DEFF Research Database (Denmark)

    Eriksson, H; Nissen, Mogens Holst

    1992-01-01

    Apart from cleaving C1s, we demonstrate for the first time that: 1) at concentrations found in serum, the activated forms of the complement components C1r in addition to C1s can cleave the heavy chain of MHC class I antigens, 2) the cleavage by C1r and C1s is seemingly dependent upon a native con...... MHC class I was shown to take place between the alpha 2- and alpha 3- domains as estimated by the Con A-Sepharose precipitation pattern on SDS-PAGE. The alpha 1/alpha 2 fragment was still shown to interact with beta 2-microglobulin as shown by immunoprecipitation....

  9. Posterior C1-C2 calcium pyrophosphate dihydrate crystal deposition disease.

    Science.gov (United States)

    Ng, Isaac Bing-Yi; Arkun, Knarik; Riesenburger, Ron I

    2016-01-01

    Calcium pyrophosphate dihydrate (CPPD) crystal deposition disease rarely occurs in the posterior aspect of the craniocervical junction (CCJ). To the best of our knowledge, there have been only 2 previously reported cases of patients with posterior CPPD lesions in this region that have led to cervical myelopathy. We report the case of a 70-year-old man presenting with neck pain and cervical myelopathy with multilevel stenosis from C1-C6. The stenosis was worst at C1-C2, secondary to compression by a CPPD lesion posterior to the spinal cord. The patient underwent a C2-C6 laminectomy and fusion with resection of the CPPD lesion. In this report, we discuss the patient and present a novel theory to explain the preponderance of CPPD lesions in the CCJ occurring anteriorly and not posteriorly to the spinal cord. PMID:26976840

  10. C1 CHEMISTRY FOR THE PRODUCTION OF ULTRA-CLEAN LIQUID TRANSPORTATION FUELS AND HYDROGEN

    Energy Technology Data Exchange (ETDEWEB)

    Gerald P. Huffman

    2003-03-31

    Faculty and students from five universities--the University of Kentucky, University of Pittsburgh, University of Utah, West Virginia University, and Auburn University--are collaborating in a research program to develop C1 chemistry processes to produce ultra-clean liquid transportation fuels and hydrogen, the zero-emissions transportation fuel of the future. The feedstocks contain one carbon atom per molecular unit. They include synthesis gas (syngas), a mixture of carbon monoxide and hydrogen produced by coal gasification or reforming of natural gas, methane, methanol, carbon dioxide, and carbon monoxide. An important objective is to develop C1 technology for the production of transportation fuel from domestically plentiful resources such as coal, coalbed methane, and natural gas. An Industrial Advisory Board with representatives from Chevron-Texaco, Eastman Chemical, Conoco-Phillips, Energy International, the Department of Defense, and Tier Associates provides guidance on the practicality of the research.

  11. C1 fractures: a review of diagnoses, management options, and outcomes.

    Science.gov (United States)

    Mead, Loren B; Millhouse, Paul W; Krystal, Jonathan; Vaccaro, Alexander R

    2016-09-01

    The atlas is subject to fracture under axial load, often due to traumatic injuries such as shallow dives and automobile accidents. These fractures account for 2-13 % of injuries to the cervical spine [Marcon RM et al. Clinics (Sao Paulo) 68(11):1455-61, 2013]. Fractures of the C1 vertebra are often difficult to diagnose, as there is often no neurological deficit or easily identifiable findings on radiographs. However, injuries to the atlas can be associated with vertebral artery injury and atlantoaxial or atlanto-occipital instability, making prompt and accurate diagnosis imperative. A detailed understanding of the anatomy, inherent stability, and common injury patterns is essential for any surgeon treating spinal trauma. This chapter explores the diagnosis and management of C1 fractures, as well as outcomes after treatment. PMID:27357228

  12. Evidence for $B^0 \\to \\chi_{c1} \\pi ^0$ at Belle

    CERN Document Server

    Kumar, R; Adachi, I; Aihara, H; Arinstein, K; Aushev, T; Aziz, T; Bakich, A M; Balagura, V; Bay, A; Bhardwaj, V; Bitenc, U; Bozek, A; Bracko, M; Browder, T E; Chen, A; Cheon, B G; Chistov, R; Cho, I S; Choi, Y; Dalseno, J; Dash, M; Drutskoy, A; Dungel, W; Eidelman, S; Gabyshev, N; Goldenzweig, P; Golob, B; Ha, H; Haba, J; Hayasaka, K; Hayashii, H; Hazumi, M; Horii, Y; Hoshi, Y; Hou, W S; Hsiung, Y B; Hyun, H J; Iijima, T; Inami, K; Ishikawa, A; Ishino, H; Itoh, R; Iwasaki, M; Kah, D H; Kang, J H; Katayama, N; Kawai, H; Kawasaki, T; Kichimi, H; Kim, S K; Kim, Y I; Kim, Y J; Kinoshita, K; Korpar, S; Krizan, P; Krokovny, P; Kuzmin, A; Kwon, Y J; Kyeong, S H; Lange, J S; Lee, J S; Lee, M J; Limosani, A; Lin, S W; Liventsev, D; Louvot, R; Mandl, F; Matyja, A; McOnie, S; Medvedeva, T; Miyabayashi, K; Miyake, H; Miyata, H; Miyazaki, Y; Mizuk, R; Mori, T; Nakamura, I; Nakano, E; Nakazawa, H; Nishida, S; Nitoh, O; Ogawa, S; Ohshima, T; Okuno, S; Ozaki, H; Pakhlov, P; Pakhlova, G; Park, C W; Park, H; Park, H K; Pestotnik, R; Piilonen, L E; Sahoo, H; Sakai, Y; Schneider, O; Sekiya, A; Senyo, K; Shapkin, M; Shiu, J G; Shwartz, B; Somov, A; Stanic, S; Staric, M; Sumiyoshi, T; Suzuki, S; Tanaka, M; Taylor, G N; Teramoto, Y; Trabelsi, K; Uehara, S; Unno, Y; Uno, S; Usov, Yu; Varner, G; Vervink, K; Wang, C C; Wang, C H; Wang, M Z; Wang, P; Watanabe, Y; Wedd, R; Won, E; Yamashita, Y; Zhang, C C; Zhang, Z P; Zhulanov, V; Zivko, T; Zupanc, A; Zyukova, O

    2008-01-01

    We present a measurement of the branching fraction for the Cabibbo- and color-suppressed $B^0 \\to \\chi_{c1}\\pi^0$ decay based on a data sample of $657\\times 10^6$ $B\\bar B$ events collected at the $\\Upsilon(4S)$ resonance with the Belle detector at the KEKB asymmetric-energy $e^+e^-$ collider. We observe a signal of $40\\pm9$ events with a significance of $4.7\\sigma$ including systematic uncertainties. The measured branching fraction is $\\mathcal {B}(B^0 \\to \\chi_{c1} \\pi^0) = (1.12\\pm 0.25(\\rm {stat.})\\pm 0.12({\\rm syst.}))\\times 10^{-5}$.

  13. Nonvortical Rashba Spin Structure on a Surface with C_{1h} Symmetry.

    Science.gov (United States)

    Annese, Emilia; Kuzumaki, Takuya; Müller, Beate; Yamamoto, Yuta; Nakano, Hiroto; Kato, Haruki; Araki, Atsushi; Ohtaka, Minoru; Aoki, Takashi; Ishikawa, Hirotaka; Hayashida, Takashi; Osiecki, Jacek R; Miyamoto, Koji; Takeichi, Yasuo; Harasawa, Ayumi; Yaji, Koichiro; Shirasawa, Tetsuroh; Nittoh, Koh-Ichi; Yang, Wooil; Miki, Kazushi; Oda, Tatsuki; Yeom, Han Woong; Sakamoto, Kazuyuki

    2016-07-01

    A totally anisotropic peculiar Rashba-Bychkov (RB) splitting of electronic bands was found on the Tl/Si(110)-(1×1) surface with C_{1h} symmetry by angle- and spin-resolved photoelectron spectroscopy and first-principles theoretical calculation. The constant energy contour of the upper branch of the RB split band has a warped elliptical shape centered at a k point located between Γ[over ¯] and the edge of the surface Brillouin zone, i.e., at a point without time-reversal symmetry. The spin-polarization vector of this state is in-plane and points almost the same direction along the whole elliptic contour. This novel nonvortical RB spin structure is confirmed as a general phenomenon originating from the C_{1h} symmetry of the surface. PMID:27419582

  14. Nonvortical Rashba Spin Structure on a Surface with C1 h Symmetry

    Science.gov (United States)

    Annese, Emilia; Kuzumaki, Takuya; Müller, Beate; Yamamoto, Yuta; Nakano, Hiroto; Kato, Haruki; Araki, Atsushi; Ohtaka, Minoru; Aoki, Takashi; Ishikawa, Hirotaka; Hayashida, Takashi; Osiecki, Jacek R.; Miyamoto, Koji; Takeichi, Yasuo; Harasawa, Ayumi; Yaji, Koichiro; Shirasawa, Tetsuroh; Nittoh, Koh-ichi; Yang, Wooil; Miki, Kazushi; Oda, Tatsuki; Yeom, Han Woong; Sakamoto, Kazuyuki

    2016-07-01

    A totally anisotropic peculiar Rashba-Bychkov (RB) splitting of electronic bands was found on the Tl /Si (110 )-(1 ×1 ) surface with C1 h symmetry by angle- and spin-resolved photoelectron spectroscopy and first-principles theoretical calculation. The constant energy contour of the upper branch of the RB split band has a warped elliptical shape centered at a k point located between Γ ¯ and the edge of the surface Brillouin zone, i.e., at a point without time-reversal symmetry. The spin-polarization vector of this state is in-plane and points almost the same direction along the whole elliptic contour. This novel nonvortical RB spin structure is confirmed as a general phenomenon originating from the C1 h symmetry of the surface.

  15. NLO NRQCD disfavors the interpretation of X(3872) as χc1(2P)

    International Nuclear Information System (INIS)

    We study χc1(2P) inclusive hadroproduction at next-to-leading order (NLO) within the factorization formalism of nonrelativistic quantum chromodynamics (NRQCD), including both the color-singlet 3P1[1] and color-octet 3S1[8] c anti c Fock states. Assuming the recently discovered X(3872) hadron to be the 2P (1++) charmonium state, we perform a fit to the cross sections measured by the CDF, CMS, and LHCb Collaborations. We either obtain an unacceptably high value of χ2 or a value of vertical stroke R2P'(0) vertical stroke incompatible with well-established potential models. We thus conclude that NLO NRQCD is incompatible with the hypothesis X(3872)≡χc1(2P).

  16. C1A Cysteine protease-cystatin interactions in leaf senescence

    OpenAIRE

    Díaz Mendoza, María Mercedes; Velasco Arroyo, Blanca; González Melendi, Pablo; Martinez Muñoz, Manuel; Diaz Rodriguez, Isabel

    2014-01-01

    Senescence-associated proteolysis in plants is a crucial process to relocalize nutrients from leaves to growing or storage tissues. The massive net degradation of proteins involves broad metabolic networks, different subcellular compartments, and several types of proteases and regulators. C1A cysteine proteases, grouped as cathepsin L-, B-, H-, and F-like according to their gene structures and phylogenetic relationships, are the most abundant enzymes responsible for the proteolytic activity d...

  17. Tomographic correlation for Magerl's technique in C1-C2 arthrodesis in children

    OpenAIRE

    Chiaramonti, Bárbara Camargo; Kim, So Yeon; Marchese, Luiz Roberto Delboni; Letaif, Olavo Biraghi; Marcon, Raphael Martus; Cristante, Alexandre Fogaça

    2013-01-01

    OBJECTIVE: To analyze through tomographic studies, the morphology and dimensions of the C1-C2 vertebrae in pediatric patients, to evaluate the possibility of application of Magerl's technique in these patients, and to contribute with data for the usage of the technique in safety. METHOD: Forty normal cervical tomographies, from patients at an age range of 24-120 months of age and from both genders, were retrospectively analyzed. Data was statistically analyzed to obtain mean value and variati...

  18. Non- (quantum) differentiable $C^1$-functions in the spaces with trivial Boyd indices

    OpenAIRE

    Potapov, Denis; Sukochev, Fyodor

    2008-01-01

    If E is a separable symmetric sequence space with trivial Boyd indices and $\\cC^E$ is the corresponding ideal of compact operators, then there exists a $C^1$-function $f_E$, a self-adjoint element $W\\in \\cC^E$ and a densely defined closed symmetric derivation $\\delta$ on $\\cC^E$ such that $W \\in Dom \\delta$, but $f_E(W) \

  19. Synthesis of metal-adeninate frameworks with high separation capacity on C2/C1 hydrocarbons

    Science.gov (United States)

    He, Yan-Ping; Zhou, Nan; Tan, Yan-Xi; Wang, Fei; Zhang, Jian

    2016-06-01

    By introducing isophthalic acid or 2,5-thiophenedicarboxylic acid to assemble with adenine and cadmium salt, two isostructural and anionic porous metal-organic frameworks (1 and 2) possessing the novel (4,8)-connected sqc topology are presented here. 1 shows permanent porosity with Langmuir surface area of 770.1 m2/g and exhibits high separation capacity on C2/C1 hydrocarbons.

  20. Rapid Reactivation of Deep Subsurface Microbes in the Presence of C-1 Compounds

    Directory of Open Access Journals (Sweden)

    Pauliina Rajala

    2015-02-01

    Full Text Available Microorganisms in the deep biosphere are believed to conduct little metabolic activity due to low nutrient availability in these environments. However, destructive penetration to long-isolated bedrock environments during construction of underground waste repositories can lead to increased nutrient availability and potentially affect the long-term stability of the repository systems, Here, we studied how microorganisms present in fracture fluid from a depth of 500 m in Outokumpu, Finland, respond to simple carbon compounds (C-1 compounds in the presence or absence of sulphate as an electron acceptor. C-1 compounds such as methane and methanol are important intermediates in the deep subsurface carbon cycle, and electron acceptors such as sulphate are critical components of oxidation processes. Fracture fluid samples were incubated in vitro with either methane or methanol in the presence or absence of sulphate as an electron acceptor. Metabolic response was measured by staining the microbial cells with fluorescent dyes that indicate metabolic activity and transcriptional response with RT-qPCR. Our results show that deep subsurface microbes exist in dormant states but rapidly reactivate their transcription and respiration systems in the presence of C-1 substrates, particularly methane. Microbial activity was further enhanced by the addition of sulphate as an electron acceptor. Sulphate- and nitrate-reducing microbes were particularly responsive to the addition of C-1 compounds and sulphate. These taxa are common in deep biosphere environments and may be affected by conditions disturbed by bedrock intrusion, as from drilling and excavation for long-term storage of hazardous waste.

  1. Impaired Autophagy in the Lipid-Storage Disorder Niemann-Pick Type C1 Disease

    OpenAIRE

    2013-01-01

    Autophagy dysfunction has been implicated in misfolded protein accumulation and cellular toxicity in several diseases. Whether alterations in autophagy also contribute to the pathology of lipid-storage disorders is not clear. Here, we show defective autophagy in Niemann-Pick type C1 (NPC1) disease associated with cholesterol accumulation, where the maturation of autophagosomes is impaired because of defective amphisome formation caused by failure in SNARE machinery, whereas the lysosomal prot...

  2. Chromatofocusing: a new method for purification of staphylococcal enterotoxins B and C1.

    OpenAIRE

    Ende, I A; Terplan, G; Kickhöfen, B; Hammer, D.K.

    1983-01-01

    A new chromatographic procedure was developed which obtained highly purified preparations of staphylococcal enterotoxins B and C1 in yields of 60% from cultures of Staphylococcus aureus and which is faster than any of the separation methods used previously. The procedure involves chromatography on carboxymethylcellulose, removal of alpha-toxin by adsorption to rabbit erythrocyte membranes, and finally, chromatofocusing as the fundamental new step. Enterotoxins were obtained in highly purified...

  3. The global uniqueness and $C^1$-regularity of geodesics in expanding impulsive gravitational waves

    CERN Document Server

    Podolsky, Jiri; Steinbauer, Roland; Svarc, Robert

    2016-01-01

    We study geodesics in the complete family of expanding impulsive gravitational waves propagating in spaces of constant curvature, that is Minkowski, de Sitter and anti-de Sitter universes. Employing the continuous form of the metric we rigorously prove existence and global uniqueness of continuously differentiable geodesics (in the sense of Filippov) and study their interaction with the impulsive wave. Thereby we justify the "$C^1$-matching procedure" used in the literature to derive their explicit form.

  4. chi_{c1} and chi_{c2} decay angular distributions at the Fermilab Tevatron

    CERN Document Server

    Kniehl, Bernd A; Palisoc, C P

    2003-01-01

    We consider the hadroproduction of chi_{c1} and chi_{c2} mesons and their subsequent radiative decays to J/psi mesons and photons in the factorization formalism of nonrelativistic quantum chromodynamics, and study the decay angular distributions, by means of helicity density matrices, in view of their sensitivity to color-octet processes. We present numerical results appropriate for the Fermilab Tevatron.

  5. Synthesis of 2-dichloromethyl-2-methyl[2-14C]-1,3-dioxolane

    International Nuclear Information System (INIS)

    The labelled compound was prepared by chlorination of [2-14C]acetone obtained from the barium salt of [1-14C]acetic acid by pyrolysis. The reaction product 1,1-dichloro[2-14C]acetone was converted to 2-dichloromethyl-2-methyl[2-14C]-1,3-dioxolane by condensation with ethylene glycol in the presence of thionyl chloride. Radiochemical yield: 62% based on [1-14C]acetic acid. (author) 7 refs

  6. A South American Prehistoric Mitogenome: Context, Continuity, and the Origin of Haplogroup C1d

    OpenAIRE

    Sans, Mónica; Figueiro, Gonzalo; Hughes, Cris E.; Lindo, John; Hidalgo, Pedro C.; Malhi, Ripan S.

    2015-01-01

    Based on mitochondrial DNA (mtDNA), it has been estimated that at least 15 founder haplogroups peopled the Americas. Subhaplogroup C1d3 was defined based on the mitogenome of a living individual from Uruguay that carried a lineage previously identified in hypervariable region I sequences from ancient and modern Uruguayan individuals. When complete mitogenomes were studied, additional substitutions were found in the coding region of the mitochondrial genome. Using a complete ancient mitogenome...

  7. Explicit Gaussian quadrature rules for C^1 cubic splines with symmetrically stretched knot sequence

    KAUST Repository

    Ait-Haddou, Rachid

    2015-06-19

    We provide explicit expressions for quadrature rules on the space of C^1 cubic splines with non-uniform, symmetrically stretched knot sequences. The quadrature nodes and weights are derived via an explicit recursion that avoids an intervention of any numerical solver and the rule is optimal, that is, it requires minimal number of nodes. Numerical experiments validating the theoretical results and the error estimates of the quadrature rules are also presented.

  8. Use of the Fluidigm C1 platform for RNA sequencing of single mouse pancreatic islet cells.

    Science.gov (United States)

    Xin, Yurong; Kim, Jinrang; Ni, Min; Wei, Yi; Okamoto, Haruka; Lee, Joseph; Adler, Christina; Cavino, Katie; Murphy, Andrew J; Yancopoulos, George D; Lin, Hsin Chieh; Gromada, Jesper

    2016-03-22

    This study provides an assessment of the Fluidigm C1 platform for RNA sequencing of single mouse pancreatic islet cells. The system combines microfluidic technology and nanoliter-scale reactions. We sequenced 622 cells, allowing identification of 341 islet cells with high-quality gene expression profiles. The cells clustered into populations of α-cells (5%), β-cells (92%), δ-cells (1%), and pancreatic polypeptide cells (2%). We identified cell-type-specific transcription factors and pathways primarily involved in nutrient sensing and oxidation and cell signaling. Unexpectedly, 281 cells had to be removed from the analysis due to low viability, low sequencing quality, or contamination resulting in the detection of more than one islet hormone. Collectively, we provide a resource for identification of high-quality gene expression datasets to help expand insights into genes and pathways characterizing islet cell types. We reveal limitations in the C1 Fluidigm cell capture process resulting in contaminated cells with altered gene expression patterns. This calls for caution when interpreting single-cell transcriptomics data using the C1 Fluidigm system. PMID:26951663

  9. A review of C1 chemistry synthesis using yttrium-stabilized zirconia catalyst

    Institute of Scientific and Technical Information of China (English)

    Antonius Indarto; Jae-Wook Choi; Hwaung Lee; Hyung Keun Song

    2008-01-01

    C1 chemistry based on synthesis gas, methane, and carbon dioxide offers many routes to industrial chemicals. The reactions related to the synthesis of gas can be classified into direct and indirect approach for making such products, such as acetic acid, dimethyl ether, and alcohol. Catalytic syngas processing is currently done at high temperatures and pressures, conditions that could be unfavorable for the life of the catalyst. Another issue of C1 chemistry is related to the methane-initiated process. It has been known that direct methane conversions are still suffering from low yields and selectivity of products resulting in unprofitable ways to produce products, such as higher hydrocarbons, methanol, and so on. However, many experts and researchers are still trying to find the best method to overcome these barriers, for example, by finding the best catalyst to reduce the high-energy barrier of the reactions and conduct only selective catalyst-surface reactions. The application of Yttria-Stabilized Zirconia (YSZ) and its combination with other metals for catalyzing purposes are increasing. The existence of an interesting site that acts as oxygen store could be the main reason for it. Moreover, formation of intermediate species on the surface of YSZ also contributes significantly in increasing the production of some specific products. Understanding the phenomena happening inside could be necessary. In this article, the use of YSZ for some C1 chemistry reactions was discussed and reviewed.

  10. Studying χc1 → ηπ+π- decays at BESIII

    Science.gov (United States)

    Kornicer, Mihajlo

    2016-05-01

    Based on 447.5 × 106 ψ(3686) produced at BESIII, we present results from an Amplitude Analysis of the ψ(3686) → γχc1; χc1 → ηπ+π- decays. Strong evidence for a two-body structure in ηπ+ + c.c. decays, with the invariant mass, width and spin consistent with the a2 (1700) is found. This decay mode of the χc1 has not been reported before. Using a dispersion relation to model the a0(980) → ηπ line shape, a non-zero value for the a0 (980) → η'π coupling is measured for the first time. The production of mesons with exotic quantum numbers, JPC = 1-+, decaying to the ηπ final state in the mass range 1.4-2.0 GeV/c2 is investigated, and the upper limits at 90% confidence level for the production of the π1(1400), π1(1600) and π1(2015) are determined.

  11. 86 The Efficacy and Safety of Human Plasma-derived C1-Inhibitor Concentrate Administered for the Treatment of Attacks in Pediatric Patients with Hereditary Angioedema Due to C1-Inhibitor Deficiency

    OpenAIRE

    Farkas, Henriette; Csuka, Dorottya; Zotter, Zsuzsanna; Szabó, Erika; Kelemen, Zsuzsanna; Varga, Lilian; Fejes, János; Harmat, George

    2012-01-01

    Background Hereditary angioedema due to C1-inhibitor deficiency (HAE-C1-INH) is a life-threatening, rare disease characterized by recurrent edematous attacks. In 50% of cases, the initial onset of symptoms occurs between 5 and 11 years of age. There are limited data on the emergency treatment of acute episodes in pediatric patients. Our aim was to analyze the efficacy and safety of human plasma-derived C1-INH concentrate in our pediatric patient population with HAE-C1-INH. Methods 50 pediatri...

  12. cDNA, deduced polypeptide structure and chromosomal assignment of human pulmonary surfactant proteolipid, SPL(pVal)

    International Nuclear Information System (INIS)

    In hyaline membrane disease of premature infants, lack of surfactant leads to pulmonary atelectasis and respiratory distress. Hydrophobic surfactant proteins of M/sub r/ = 5000-14,000 have been isolated from mammalian surfactants which enhance the rate of spreading and the surface tension lowering properties of phospholipids during dynamic compression. The authors have characterized the amino-terminal amino acid sequence of pulmonary proteolipids from ether/ethanol extracts of bovine, canine, and human surfactant. Two distinct peptides were identified and termed SPL(pVal) and SPL(Phe). An oligonucleotide probe based on the valine-rich amino-terminal amino acid sequence of SPL(pVal) was utilized to isolate cDNA and genomic DNA encoding the human protein, termed surfactant proteolipid SPL(pVal) on the basis of its unique polyvaline domain. The primary structure of a precursor protein of 20,870 daltons, containing the SPL(pVal) peptide, was deduced from the nucleotide sequence of the cDNAs. Hybrid-arrested translation and immunoprecipitation of labeled translation products of human mRNA demonstrated a precursor protein, the active hydrophobic peptide being produced by proteolytic processing. Two classes of cDNAs encoding SPL(pVal) were identified. Human SPL(pVal) mRNA was more abundant in the adult than in fetal lung. The SPL(pVal) gene locus was assigned to chromosome 8

  13. A blind trial evaluation of a crime scene methodology for deducing impact velocity and droplet size from circular bloodstains.

    Science.gov (United States)

    Hulse-Smith, Lee; Illes, Mike

    2007-01-01

    In a previous study, mechanical engineering models were utilized to deduce impact velocity and droplet volume of circular bloodstains by measuring stain diameter and counting spines radiating from their outer edge. A blind trial study was subsequently undertaken to evaluate the accuracy of this technique, using an applied, crime scene methodology. Calculations from bloodstains produced on paper, drywall, and wood were used to derive surface-specific equations to predict 39 unknown mock crime scene bloodstains created over a range of impact velocities (2.2-5.7 m/sec) and droplet volumes (12-45 microL). Strong correlations were found between expected and observed results, with correlation coefficients ranging between 0.83 and 0.99. The 95% confidence limit associated with predictions of impact velocity and droplet volume was calculated for paper (0.28 m/sec, 1.7 microL), drywall (0.37 m/sec, 1.7 microL), and wood (0.65 m/sec, 5.2 microL). PMID:17209911

  14. Comparison of the chromosomal localization of murine and human glucocerebrosidase genes and of the deduced amino acid sequences

    International Nuclear Information System (INIS)

    To study structure-function relationships and molecular evolution, the authors determined the nucleotide sequence and chromosomal location of the gene encoding murine glucocerebrosidase. In the protein coding region of the murine cDNA, the nucleotide sequence and the corresponding deduced amino acid sequences were 82% and 86% identical to the respective humans sequences. All five amino acids presently known to be essential for normal enzymatic activity were conserved between mouse and man. The murine enzyme had a single deletion relative to the human enzyme at amino acid number 273. One ATG translation initiation signal was present in the mouse sequence in contrast to the human sequence, where two start codons have been reported. Nucleotide sequencing of a clone derived from murine genomic DNA revealed that the murine signal for translation initiation was located in exon 2. The locations of all 10 introns were conserved among mouse and man. They mapped the genetic locus for glucocerebrosidase to mouse chromosome 3, at a position 7.6 ± 3.2 centimorgans from the locus for the β subunit of nerve growth factor. Comparison of linkage relationships in the human and murine genome indicates that these closely linked mouse genes are also syntenic on human chromosome 1 but in positions that span the centromere

  15. Deducing receptor signaling parameters from in vivo analysis: LuxN/AI-1 quorum sensing in Vibrio harveyi

    Science.gov (United States)

    Swem, Lee R.; Swem, Danielle L.; Wingreen, Ned S.; Bassler, Bonnie L.

    2008-01-01

    Summary Quorum sensing, a process of bacterial cell-cell communication, relies on production, detection, and response to autoinducer signaling molecules. Here we focus on LuxN, a nine transmembrane domain protein from Vibrio harveyi, and the founding example of membrane-bound receptors for acyl-homoserine lactone (AHL) autoinducers. Previously, nothing was known about signal recognition by membrane-bound AHL receptors. We used mutagenesis and suppressor analyses to identify the AHL-binding domain of LuxN, and discovered LuxN mutants that confer decreased and increased AHL sensitivity. Our analysis of dose-response curves of multiple LuxN mutants pins these inverse phenotypes on quantifiable opposing shifts in the free-energy bias of LuxN for its kinase and phosphatase states. To extract signaling parameters, we exploited a strong LuxN antagonist, one of fifteen small-molecule antagonists we identified. We find that quorum-sensing-mediated communication can be manipulated positively and negatively to control bacterial behavior, and that signaling parameters can be deduced from in vivo data. PMID:18692469

  16. Spontaneous C1 anterior arch fracture as a postoperative complication of foramen magnum decompression for Chiari malformation type 1

    OpenAIRE

    Hirano, Yoshitaka; Sugawara, Atsushi; Mizuno, Junichi; Takeda, Masaaki; Watanabe, Kazuo; OGASAWARA, Kuniaki

    2011-01-01

    Background: C1 fracture accounts for 2% of all spinal column injuries and 10% of cervical spine fractures, and is most frequently caused by motor vehicle accidents and falls. We present a rare case of C1 anterior arch fracture following standard foramen magnum decompression for Chiari malformation type 1. Case Description: A 63-year-old man underwent standard foramen magnum decompression (suboccipital craniectomy and C1 laminectomy) under a diagnosis of Chiari malformation type 1 with syringo...

  17. Complement protein C1q directs macrophage polarization and limits inflammasome activity during the uptake of apoptotic cells

    Science.gov (United States)

    Benoit, Marie E.; Clarke, Elizabeth V.; Morgado, Pedro; Fraser, Deborah A.; Tenner, Andrea J.

    2012-01-01

    Deficiency in C1q, the recognition component of the classical complement cascade and a pattern recognition receptor involved in apoptotic cell clearance, leads to lupus-like auto-immune diseases characterized by auto-antibodies to self proteins and aberrant innate immune cell activation likely due to impaired clearance of apoptotic cells. Here, we developed an autologous system using primary human lymphocytes and monocyte-derived macrophages (HMDMs) to characterize the effect of C1q on macrophage gene expression profiles during the uptake of apoptotic cells. C1q bound to autologous apoptotic lymphocytes modulated expression of genes associated with JAK/STAT signaling, chemotaxis, immunoregulation and NLRP3 inflammasome activation in LPS-stimulated HMDMs. Specifically, C1q sequentially induced type I interferons (IFNs), IL-27 and IL-10 in LPS-stimulated HMDMs and IL-27 in HMDMs when incubated with AL conditioned media. Co-incubation with C1q tails prevented the induction of type I IFNs and IL-27 in a dose dependent manner and neutralization of type I IFNs partially prevented IL-27 induction by C1q. Finally, C1q decreased procaspase-1 cleavage and caspase-1 dependent cleavage of IL-1β suggesting potent inhibitory effect of C1q on inflammasome activation. These results identify specific molecular pathways induced by C1q to suppress macrophage inflammation providing potential therapeutic targets to control macrophage polarization, and thus inflammation and autoimmunity. PMID:22523386

  18. Mechanism of progestin resistance in endometrial precancer/cancer through Nrf2-AKR1C1 pathway.

    Science.gov (United States)

    Wang, Yiying; Wang, Yue; Zhang, Zhenbo; Park, Ji-Young; Guo, Donghui; Liao, Hong; Yi, Xiaofang; Zheng, Yu; Zhang, Donna; Chambers, Setsuko K; Zheng, Wenxin

    2016-03-01

    Progestin resistance is a main obstacle for endometrial precancer/cancer conservative therapy. Therefore, biomarkers to predict progestin resistance and studies to gain a more detailed understanding of the mechanism are needed. The antioxidant Nrf2-AKR1C1 signal pathway exerts chemopreventive activity. However whether it plays a role in progestin resistance has not been explored. In this study, elevated levels of AKR1C1 and Nrf2 were found in progestin-resistant endometrial epithelia, but not in responsive endometrial glands. Exogenous overexpression of Nrf2/AKR1C1 resulted in progestin resistance. Inversely, silencing of Nrf2 or AKR1C1 rendered endometrial cancer cells more susceptible to progestin treatment. Moreover, medroxyprogesterone acetate withdrawal resulted in suppression of Nrf2/AKR1C1 expression accompanied by a reduction of cellular proliferative activity. In addition, brusatol and metformin overcame progestin resistance by down-regulating Nrf2/AKR1C1 expression. Our findings suggest that overexpression of Nrf2 and AKR1C1 in endometrial precancer/cancer may be part of the molecular mechanisms underlying progestin resistance. If validated in a larger cohort, overexpression of Nrf2 and AKR1C1 may prove to be useful biomarkers to predict progestin resistance. Targeting the Nrf2/AKR1C1 pathway may represent a new therapeutic strategy for treatment of endometrial hyperplasia/cancer. PMID:26824415

  19. Clinical Presentation of Cervical Myelopathy at C1–2 Level

    Science.gov (United States)

    Takebayashi, Tsuneo; Terashima, Yoshinori; Tsuda, Hajime; Yoshimoto, Mitsunori; Yamashita, Toshihiko

    2016-01-01

    Study Design Single-center retrospective study. Purpose To clarify the clinical features of cervical myelopathy at the C1–2 level. Overview of Literature Methods for distinguishing the affected level based on myelomere symptoms or dysfunction of the conducting pathway were established. However, no symptoms have been identified as being specific to the C1–2 level segment. Methods We evaluated 24 patients with cervical myelopathy due to spinal cord compression at the C1–2 level. Preoperative neurological assessment were investigated and compared with the rate and site of compression of the spinal cord using computed tomography-myelography. Results Impaired temperature and pain sensation were confirmed in 18 of the 24 patients with that localized to the upper arms (n=3), forearm (n=9), both (n=2), and whole body (n=4). Muscle weakness was observed in 18 patients, muscle weakness extended from the biceps brachii to the abductor digiti minimi in 10 patients, and in the whole body in 8 patients. Deep tendon reflexes were normal in 10 patients, whereas hyperactive deep tendon reflexes were noted in 14 patients. The rate of spinal cord compression was significantly higher in patients with perceptual dysfunction and muscle weakness compared with those with no dysfunction. However, no significant difference in the rate and site of compression was identified in those with dysfunction. Conclusions Perceptual dysfunction and muscle weakness localized to the upper limbs was observed in 58% and 42% of patients, respectively. Neurological abnormalities, such as perceptual dysfunction and muscle weakness, were visualized in patients with marked compression.

  20. Global modeling of the C1-C3 alkyl nitrates using STOCHEM-CRI

    Science.gov (United States)

    Khan, M. A. H.; Cooke, M. C.; Utembe, S. R.; Morris, W. C.; Archibald, A. T.; Derwent, R. G.; Jenkin, M. E.; Orr-Ewing, A. J.; Higgins, C. M.; Percival, C. J.; Leather, K. E.; Shallcross, D. E.

    2015-12-01

    The atmospheric global budget and distribution of C1-C3 alkyl nitrates have been investigated using a global three-dimensional chemistry transport model, STOCHEM-CRI. Alkyl nitrates (RONO2) are significant NOx reservoir species and the more detailed VOC oxidation mechanism (CRI v2-R5) leads to greater photochemical production. RONO2 are significant sources of NOx in regions remote from NOx sources. The study shows that the global burden and the atmospheric life-time of C1-C3 alkyl nitrates are 113 Gg and 9-10 days, respectively, which are in excellent agreement with estimates established by previous studies. The abundance of alkyl nitrates have been found to be higher in the continental atmosphere, with CH3ONO2 mixing ratios up to 20 ppt over the Amazon rainforest. Up to 15, 10, 2, and 5 ppt of modelled CH3ONO2, C2H5ONO2, n-C3H7ONO2 and i-C3H7ONO2 have been found in the northern hemisphere over regions with large anthropogenic emissions of NOx and VOCs. The combination of atmospheric production and long-range transport led to high alkyl nitrate levels at high latitudes. The model performance for C1-C3 alkyl nitrates was established using observations from nine flights and nine field campaigns. The comparison shows a tendency towards model under-prediction of the observations, particularly in the southern hemispheric marine boundary layer, possibly due to the absence of oceanic production mechanisms and air-sea exchange processes in the model. The discrepancies between model and observed seasonal cycles, especially of CH3ONO2, in both hemispheres are discussed.

  1. Relativistic Force Field: Parametrization of (13)C-(1)H Nuclear Spin-Spin Coupling Constants.

    Science.gov (United States)

    Kutateladze, Andrei G; Mukhina, Olga A

    2015-11-01

    Previously, we reported a reliable DU8 method for natural bond orbital (NBO)-aided parametric scaling of Fermi contacts to achieve fast and accurate prediction of proton-proton spin-spin coupling constants (SSCC) in (1)H NMR. As sophisticated NMR experiments for precise measurements of carbon-proton SSCCs are becoming more user-friendly and broadly utilized by the organic chemistry community to guide and inform the process of structure determination of complex organic compounds, we have now developed a fast and accurate method for computing (13)C-(1)H SSCCs. Fermi contacts computed with the DU8 basis set are scaled using selected NBO parameters in conjunction with empirical scaling coefficients. The method is optimized for inexpensive B3LYP/6-31G(d) geometries. The parametric scaling is based on a carefully selected training set of 274 ((3)J), 193 ((2)J), and 143 ((1)J) experimental (13)C-(1)H spin-spin coupling constants reported in the literature. The DU8 basis set, optimized for computing Fermi contacts, which by design had evolved from optimization of a collection of inexpensive 3-21G*, 4-21G, and 6-31G(d) bases, offers very short computational (wall) times even for relatively large organic molecules containing 15-20 carbon atoms. The most informative SSCCs for structure determination, i.e., (3)J, were computed with an accuracy of 0.41 Hz (rmsd). The new unified approach for computing (1)H-(1)H and (13)C-(1)H SSCCs is termed "DU8c". PMID:26414291

  2. Allelic variants of DYX1C1 are not associated with dyslexia in India

    OpenAIRE

    Saviour, Pushpa; Kumar, Satish; Kiran, U; Ravuri, Rajasekhara Reddy; Rao, V R; Ramachandra, Nallur Basappa

    2008-01-01

    Dyslexia is a hereditary neurological disorder that manifests as an unexpected difficulty in learning to read despite adequate intelligence, education, and normal senses. The prevalence of dyslexia ranges from 3 to 15% of the school aged children. Many genetic studies indicated that loci on 6p21.3, 15q15-21, and 18p11.2 have been identified as promising candidate gene regions for dyslexia. Recently, it has been suggested that allelic variants of gene, DYX1C1 influence dyslexia. In the present...

  3. Allelic variants of DYX1C1 are not associated with dyslexia in India

    OpenAIRE

    Saviour Pushpa; Kumar Satish; Kiran U; Ravuri Rajasekhara; Rao V.; Ramachandra Nallur

    2008-01-01

    Dyslexia is a hereditary neurological disorder that manifests as an unexpected difficulty in learning to read despite adequate intelligence, education, and normal senses. The prevalence of dyslexia ranges from 3 to 15% of the school aged children. Many genetic studies indicated that loci on 6p21.3, 15q15-21, and 18p11.2 have been identified as promising candidate gene regions for dyslexia. Recently, it has been suggested that allelic variants of gene, DYX1C1 influence dyslexia. In the ...

  4. Optical spectral observations of a flickering white-light kernel in a C1 solar flare

    OpenAIRE

    Kowalski, Adam F.; Cauzzi, Gianna; Fletcher, Lyndsay

    2015-01-01

    We analyze optical spectra of a two-ribbon, long duration C1.1 flare that occurred on 18 Aug 2011 within AR 11271 (SOL2011-08-18T15:15). The impulsive phase of the flare was observed with a comprehensive set of space-borne and ground-based instruments, which provide a range of unique diagnostics of the lower flaring atmosphere. Here we report the detection of enhanced continuum emission, observed in low-resolution spectra from 3600 \\AA\\ to 4550 \\AA\\ acquired with the Horizontal Spectrograph a...

  5. iAK692: A genome-scale metabolic model of Spirulina platensis C1

    Directory of Open Access Journals (Sweden)

    Klanchui Amornpan

    2012-06-01

    Full Text Available Abstract Background Spirulina (Arthrospira platensis is a well-known filamentous cyanobacterium used in the production of many industrial products, including high value compounds, healthy food supplements, animal feeds, pharmaceuticals and cosmetics, for example. It has been increasingly studied around the world for scientific purposes, especially for its genome, biology, physiology, and also for the analysis of its small-scale metabolic network. However, the overall description of the metabolic and biotechnological capabilities of S. platensis requires the development of a whole cellular metabolism model. Recently, the S. platensis C1 (Arthrospira sp. PCC9438 genome sequence has become available, allowing systems-level studies of this commercial cyanobacterium. Results In this work, we present the genome-scale metabolic network analysis of S. platensis C1, iAK692, its topological properties, and its metabolic capabilities and functions. The network was reconstructed from the S. platensis C1 annotated genomic sequence using Pathway Tools software to generate a preliminary network. Then, manual curation was performed based on a collective knowledge base and a combination of genomic, biochemical, and physiological information. The genome-scale metabolic model consists of 692 genes, 837 metabolites, and 875 reactions. We validated iAK692 by conducting fermentation experiments and simulating the model under autotrophic, heterotrophic, and mixotrophic growth conditions using COBRA toolbox. The model predictions under these growth conditions were consistent with the experimental results. The iAK692 model was further used to predict the unique active reactions and essential genes for each growth condition. Additionally, the metabolic states of iAK692 during autotrophic and mixotrophic growths were described by phenotypic phase plane (PhPP analysis. Conclusions This study proposes the first genome-scale model of S. platensis C1, iAK692, which is a

  6. C^1-approximate solutions of second-order singular ordinary differential equations

    Directory of Open Access Journals (Sweden)

    George L. Karakostas

    2010-09-01

    Full Text Available In this work a new method is developed to obtain C^1-approximate solutions of initial and boundary-value problems generated from a one - parameter second order singular ordinary differential equation. Information about the order of approximation is also given by introducing the so called growth index of a function. Conditions are given for the existence of such approximations for initial and boundary-value problems of several kinds. Examples associated with the corresponding graphs of the approximate solutions, for some values of the parameter, are also given.

  7. W-algebras, new rational models and completeness of the c=1 classification

    International Nuclear Information System (INIS)

    Two series of W-algebras with two generators are constructed from chiral vertex operators of a free field representation. If c=1-24k, there exists a W(2,3k) algebra for k element of Z+/2 and a W(2,8k) algebra for k element of Z+/4. All possible lowest-weight representations, their characters and fusion rules are calculated proving that these theories are rational. It is shown, that these non-unitary theories complete the classification of all rational theories with effective central charge ceff=1. The results are generalized to the case of extended supersymmetric conformal algebras. (orig.)

  8. W-algebras, new rational models and completeness of the c=1 classification

    International Nuclear Information System (INIS)

    Two series of W-algebras with two generators are constructed from chiral vertex operators of a free field representation. If c = 1 - 24 k, there exists a W(2,3k) algebra for kelement of Z+/2 and a W (2,8k) algebra for k element of Z+/4. All possible lowest-weight representations, their characters and fusion rules are calculated proving that these therories are rational. It is shown, that these non-unitary theories complete the classification of all rational therories with effective central charge ceff = 1. The results are generalized to the case of extended supersymmetric conformal algebras. (orig.)

  9. Isolation and characterization of a cyanide dihydratase from Bacillus pumilus C1.

    OpenAIRE

    Meyers, P R; Rawlings, D E; Woods, D. R.; Lindsey, G G

    1993-01-01

    A cyanide-degrading enzyme from Bacillus pumilus C1 has been purified and characterized. This enzyme consisted of three polypeptides of 45.6, 44.6, and 41.2 kDa; the molecular mass by gel filtration was 417 kDa. Electron microscopy revealed a multimeric, rod-shaped protein approximately 9 by 50 nm. Cyanide was rapidly degraded to formate and ammonia. Enzyme activity was optimal at 37 degrees C and pH 7.8 to 8.0. Activity was enhanced by Sc3+, Cr3+, Fe3+, and Tb3+; enhancement was independent ...

  10. Development of Cotton leaf curl virus resistant transgenic cotton using antisense ßC1 gene.

    Science.gov (United States)

    Sohrab, Sayed Sartaj; Kamal, Mohammad A; Ilah, Abdul; Husen, Azamal; Bhattacharya, P S; Rana, D

    2016-05-01

    Cotton leaf curl virus (CLCuV) is a serious pathogen causing leaf curl disease and affecting the cotton production in major growing areas. The transgenic cotton (Gossypium hirsutum cv. Coker 310) plants were developed by using βC1 gene in antisense orientation gene driven by Cauliflower mosaic virus-35S promoter and nos (nopaline synthase) terminator and mediated by Agrobacterium tumefaciens transformation and somatic embryogenesis system. Molecular confirmation of the transformants was carried out by polymerase chain reaction (PCR) and Southern blot hybridization. The developed transgenic and inoculated plants remained symptomless till their growth period. In conclusion, the plants were observed as resistant to CLCuV. PMID:27081361

  11. Indirect 13C-1H spin-spin coupling constants in 3-carene

    International Nuclear Information System (INIS)

    The potential value of the indirect constants nJCH (n ≥ 2) for the analysis of the compositions and spatial structures of organic compounds is known, but the usual procedures for their measurement from proton-linked 13C NMR spectra are ineffective in the case of terpenoids because of the complex multiplet structures of the signals. In this paper, using (+)-3-carene as an example, the possibility is demonstrated of measuring the complete set of indirect 13C-1H spin-spin coupling constants with the aid of two-dimensional J-resolved 13C NMR with selective excitation of protons. 6 refs

  12. Association between nasal carriage of Staphylococcus aureus and the human complement cascade activator serine protease C1 inhibitor (C1INH) valine vs. methionine polymorphism at amino acid position 480.

    NARCIS (Netherlands)

    Emonts, M.; Jongh, C.E. de; Houwing-Duistermaat, J.J.; Leeuwen, W.B. van; Groot, R. de; Verbrugh, H.A.; Hermans, P.W.M.; Belkum, A. van

    2007-01-01

    Staphylococcus aureus produces compounds that interfere with complement deposition. We hypothesized that humans have developed countermeasures to staphylococcal complement evasion and we screened for single nucleotide polymorphisms in the serine protease C1 inhibitor (C1INH) gene at amino acid posit

  13. Subtype C1 persistent infection of HHV-8 in a PEL patient.

    Science.gov (United States)

    Metaxa-Mariatou, V; Papaioannou, D; Loli, A; Papadopoulou, I; Gazouli, M; Mavroudis, P; Nasioulas, G

    2005-10-01

    PEL, a rare type of lymphoma constituting less than 5% of NHLs, has been recently identified as a distinct clinical and pathological entity among the B-cell lymphomas, with characteristic morphologic, immunophenotypic, molecular and viral features. ICC, PCR, RT-PCR and sequencing were carried out in biologicals samples from a 44-year-old, non-smoker Caucasian male patient of Greek nationality, HIV-1 negative and HCV positive. The ICC results showed CD30 + , Vimentin + , EMA + , Ki67 + , Pankeratin- and negative to B and T antibodies. In addition, HHV-8 was detected in pleural fluid. Examination of blood samples of the patient over a period of nearly two years showed a persistent infection of HHV-8. Phylogenetic analysis revealed a close relation to the C1 variant of HHV-8. The samples was also found EBV negative by PCR. Using a combination of clinical, morphological, immunohistochemical features and molecular biology techniques in this study we document a PEL case with persistent HHV-8 of genotype C1 infection. PMID:16194897

  14. C1 CHEMISTRY FOR THE PRODUCTION OF ULTRA-CLEAN LIQUID TRANSPORTATION FUELS AND HYDROGEN

    Energy Technology Data Exchange (ETDEWEB)

    Gerald P. Huffman

    2004-03-31

    Faculty and students from five universities--the University of Kentucky, University of Pittsburgh, University of Utah, West Virginia University, and Auburn University--are collaborating in a research program to develop C1 chemistry processes to produce ultra-clean liquid transportation fuels and hydrogen, the zero-emissions transportation fuel of the future. The feedstocks contain one carbon atom per molecular unit. They include synthesis gas (syngas), a mixture of carbon monoxide and hydrogen produced by coal gasification or reforming of natural gas, methane, methanol, carbon dioxide, and carbon monoxide. An important objective is to develop C1 technology for the production of liquid transportation fuel and hydrogen from domestically plentiful resources such as coal, coalbed methane, and natural gas. An Industrial Advisory Board with representatives from Chevron-Texaco, Eastman Chemical, Conoco-Phillips, the Air Force Research Laboratory, the U.S. Army National Automotive Center (Tank & Automotive Command--TACOM), and Tier Associates provides guidance on the practicality of the research. The current report presents results obtained in this research program during the six months of the subject contract from October 1, 2002 through March 31, 2003. The results are presented in thirteen detailed reports on research projects headed by various faculty members at each of the five CFFS Universities. Additionally, an Executive Summary has been prepared that summarizes the principal results of all of these projects during the six-month reporting period.

  15. C1 Chemistry for the Production of Ultra-Clean Liquid Transportation Fuels and Hydrogen

    Energy Technology Data Exchange (ETDEWEB)

    Gerald P. Huffman

    2005-03-31

    Faculty and students from five universities--the University of Kentucky, University of Pittsburgh, University of Utah, West Virginia University, and Auburn University--are collaborating in a research program to develop C1 chemistry processes to produce ultra-clean liquid transportation fuels and hydrogen, the zero-emissions transportation fuel of the future. The feedstocks contain one carbon atom per molecular unit. They include synthesis gas (syngas), a mixture of carbon monoxide and hydrogen produced by coal gasification or reforming of natural gas, methane, methanol, carbon dioxide, and carbon monoxide. An important objective is to develop C1 technology for the production of liquid transportation fuel and hydrogen from domestically plentiful resources such as coal, coalbed methane, and natural gas. An Industrial Advisory Board with representatives from Chevron-Texaco, Eastman Chemical, Conoco-Phillips, the Air Force Research Laboratory, the U.S. Army National Automotive Center (Tank & Automotive Command--TACOM), and Tier Associates provides guidance on the practicality of the research. The current report presents results obtained in this research program during the six months of the subject contract from October 1, 2002 through March 31, 2003. The results are presented in thirteen detailed reports on research projects headed by various faculty members at each of the five CFFS Universities. Additionally, an Executive Summary has been prepared that summarizes the principal results of all of these projects during the six-month reporting period.

  16. C1 Chemistry for the Production of Ultra-Clean Liquid Transportation Fuels and Hydrogen

    Energy Technology Data Exchange (ETDEWEB)

    Gerald P. Huffman

    2003-03-31

    Faculty and students from five universities--the University of Kentucky, University of Pittsburgh, University of Utah, West Virginia University, and Auburn University--are collaborating in a research program to develop C1 chemistry processes to produce ultra-clean liquid transportation fuels and hydrogen, the zero-emissions transportation fuel of the future. The feedstocks contain one carbon atom per molecular unit. They include synthesis gas (syngas), a mixture of carbon monoxide and hydrogen produced by coal gasification or reforming of natural gas, methane, methanol, carbon dioxide, and carbon monoxide. An important objective is to develop C1 technology for the production of transportation fuel from domestically plentiful resources such as coal, coalbed methane, and natural gas. An Industrial Advisory Board with representatives from Chevron-Texaco, Eastman Chemical, Conoco-Phillips, Energy International, the Department of Defense, and Tier Associates provides guidance on the practicality of the research. The current report presents results obtained in this research program during the first six months of the subject contract (DE-FC26-02NT-4159), from October 1, 2002 through March 31, 2003.

  17. Ecallantide is a novel treatment for attacks of hereditary angioedema due to C1 inhibitor deficiency

    Directory of Open Access Journals (Sweden)

    Farkas H

    2011-05-01

    Full Text Available Henriette Farkas, Lilian Varga3rd Department of Internal Medicine, Semmelweis University, Budapest, HungaryAbstract: Hereditary angioedema (HAE resulting from the deficiency of the C1 inhibitor protein is a rare disease, characterized by paroxysms of edema formation in the subcutis and in the submucosa. Edema can cause obstruction of the upper airway, which may lead to suffocation. Prompt elimination of edema is necessary to save patients from this life-threatening condition. Essentially, these edematous attacks are related to the activation of the kinin-kallikrein system and the consequent release of bradykinin. Ecallantide (known as DX-88 previously, a potent and specific inhibitor of plasma kallikrein is an innovative medicinal product. This is the only agent approved recently by the FDA for all localizations of edematous HAE attacks. Its advantages include no risk of viral contamination, high selectivity, very rapid onset of action, good tolerability, and straightforward subcutaneous administration. Owing to the risk of anaphylaxis, ecallantide should be administered by a health care professional. A postmarketing survey to improve risk-assessment and risk-minimization has been launched. The results of these studies may lead to the approval of ecallantide for self-administration.Keywords: hereditary angioedema, C1-inhibitor deficiency, treatment, bradykinin, kallikrein inhibitor, subcutaneous administration

  18. Formation of carbon nano- and micro-structures on C+1 irradiated copper surfaces

    International Nuclear Information System (INIS)

    A series of experiments has identified mechanisms of carbon nano- and micro-structure formation at room temperature, without catalyst and in the environment of immiscible metallic surroundings. The structures include threaded nano fibres, graphitic sheets and carbon onions. Copper as substrate was used due to its immiscibility with carbon. Energetic carbon ions (C+1) of 0.2–2.0 MeV irradiated Cu targets. Cu substrates, apertures and 3 mm dia TEM Cu grids were implanted with the carbon. We observed wide range of μm-size structures formed on Cu grids and along the edges of the irradiated apertures. These are shown to be threaded nano fibers (TNF) of few μm thicknesses with lengths varying from 10 to 3000 μm. Secondary electron microscopy (SEM) identifies the μm-size structures while Confocal microscopy was used to learn about the mechanisms by which C+1 irradiated Cu provides the growth environment. Huge carbon onions of diameters ranging from hundreds of nm to μm were observed in the as-grown and annealed samples. Transformations of the nanostructures were observed under prolonged electron irradiations of SEM and TEM. A mechanism for the formation of carbon nano- and micro-structures is proposed.

  19. Borel and Stokes Nonperturbative Phenomena in Topological String Theory and c=1 Matrix Models

    CERN Document Server

    Pasquetti, Sara

    2010-01-01

    We address the nonperturbative structure of topological strings and c=1 matrix models, focusing on understanding the nature of instanton effects alongside with exploring their relation to the large-order behavior of the 1/N expansion. We consider the Gaussian, Penner and Chern-Simons matrix models, together with their holographic duals, the c=1 minimal string at self-dual radius and topological string theory on the resolved conifold. We employ Borel analysis to obtain the exact all-loop multi-instanton corrections to the free energies of the aforementioned models, and show that the leading poles in the Borel plane control the large-order behavior of perturbation theory. We understand the nonperturbative effects in terms of the Schwinger effect and provide a semiclassical picture in terms of eigenvalue tunneling between critical points of the multi-sheeted matrix model effective potentials. In particular, we relate instantons to Stokes phenomena via a hyperasymptotic analysis, providing a smoothing of the nonp...

  20. Utilization of metabonomics to identify serum biomarkers in murine H22 hepatocarcinoma and deduce antitumor mechanism of Rhizoma Paridis saponins.

    Science.gov (United States)

    Qiu, Peiyu; Man, Shuli; Yang, He; Fan, Wei; Yu, Peng; Gao, Wenyuan

    2016-08-25

    Murine H22 hepatocarcinoma model is so popular to be used for the preclinical anticancer candidate's evaluation. However, the metabolic biomarkers of this model were not identified. Meanwhile, Rhizoma Paridis saponins (RPS) as natural products have been found to show strong antitumor activity, while its anti-cancer mechanism is not clear. To search for potential metabolite biomarkers of this model, serum metabonomics approach was applied to detect the variation of metabolite biomarkers and the related metabolism genes and signaling pathway were used to deduce the antitumor mechanisms of RPS. As a result, ten serum metabolites were identified in twenty-four mice including healthy mice, non-treated cancer mice, RPS-treated cancer mice and RPS-treated healthy mice. RPS significantly decreased tumor weight correlates to down-regulating lactate, acetate, N-acetyl amino acid and glutamine signals (p p53 and PTEN, and suppressed FASN to inhibit lipogenesis. What's more, RPS repressed Myc and GLS expression and decreased glutamine level. The regulating PI3K/Akt/mTOR and HIF-1α/Myc/Ras networks also participated in these metabolic changes. Taken together, RPS suppressed ATP product made the tumor growth slow, which indicated a good anti-cancer effect and new angle for understanding the mechanism of RPS. In conclusion, this study demonstrated that the utility of (1)H NMR metabolic profiles taken together with tumor weight and viscera index was a promising screening tool for evaluating the antitumor effect of candidates. In addition, RPS was a potent anticancer agent through inhibiting cancer cellular metabolism to suppress proliferation in hepatoma H22 tumor murine, which promoted the application of RPS in the future. PMID:27369806

  1. Molecular basis of hereditary C1q deficiency-revisited: identification of several novel disease-causing mutations

    DEFF Research Database (Denmark)

    Schejbel, L; Skattum, L; Hagelberg, S; Ahlin, A; Schiller, B; Berg, Steve; Genel, F; Truedsson, L; Garred, P

    2011-01-01

    increased susceptibility to bacterial infections. However, the clinical symptoms may vary. For long, the molecular basis of C1q deficiency was ascribed to only six different mutations. In the present report, we describe five new patients with C1q deficiency, present the 12 causative mutations described till...

  2. Dietary cholesterol induces trafficking of intestinal Niemann-Pick Type C1 Like 1 from the brush border to endosomes

    DEFF Research Database (Denmark)

    Skov, Marianne; Tønnesen, Carina K; Hansen, Gert H;

    2011-01-01

    The transmembrane protein Niemann-Pick C1 Like 1 (NPC1L1) belongs to the Niemann-Pick C1 (NPC1) family of cholesterol transporters and is mainly expressed in the liver and the small intestine. NPC1L1 is believed to be the main transporter responsible for the absorption of dietary cholesterol. Like...

  3. Self-administration of intravenous C1-inhibitor therapy for hereditary angioedema and associated quality of life benefits

    DEFF Research Database (Denmark)

    Bygum, Anette; Andersen, Klaus Ejner; Mikkelsen, Carsten Sauer

    2009-01-01

    Hereditary angioedema (HAE) is often debilitating with a serious effect on quality of life (QOL). Treatment of acute HAE attacks is usually with C1 esterase inhibitor (C1-INH) concentrates; however, treatment can be delayed by patients' travel time for attending emergency units. We assessed the...

  4. C1, a highly potent novel curcumin derivative, binds to tubulin, disrupts microtubule network and induces apoptosis

    Science.gov (United States)

    Srivastava, Shalini; Mishra, Satyendra; Surolia, Avadhesha; Panda, Dulal

    2016-01-01

    We have synthesized a curcumin derivative, 4-{5-(4-hydroxy-3-methoxy-phenyl)-2-[3-(4-hydroxy-3-methoxy-phenyl)-acryloyl]-3-oxo-penta-1,4-dienyl}-piperidine-1-carboxylic acid tert-butyl ester (C1) that displays much stronger antiproliferative activity against various types of cancer cells including multidrug resistance cells than curcumin. C1 depolymerized both interphase and mitotic microtubules in MCF-7 cells and also inhibited the reassembly of microtubules in these cells. C1 inhibited the polymerization of purified tubulin, disrupted the lattice structure of microtubules and suppressed their GTPase activity in vitro. The compound bound to tubulin with a dissociation constant of 2.8±1 μM and perturbed the secondary structures of tubulin. Further, C1 treatment reduced the expression of Bcl2, increased the expression of Bax and down regulated the level of a key regulator of p53, murine double minute 2 (Mdm2) (S166), in MCF-7 cells. C1 appeared to induce p53 mediated apoptosis in MCF-7 cells. Interestingly, C1 showed more stability in aqueous buffer than curcumin. The results together showed that C1 perturbed microtubule network and inhibited cancer cells proliferation more efficiently than curcumin. The strong antiproliferative activity and improved stability of C1 indicated that the compound may have a potential as an anticancer agent. PMID:26980197

  5. 86 The Efficacy and Safety of Human Plasma-derived C1-Inhibitor Concentrate Administered for the Treatment of Attacks in Pediatric Patients with Hereditary Angioedema Due to C1-Inhibitor Deficiency

    Science.gov (United States)

    Farkas, Henriette; Csuka, Dorottya; Zotter, Zsuzsanna; Szabó, Erika; Kelemen, Zsuzsanna; Varga, Lilian; Fejes, János; Harmat, George

    2012-01-01

    Background Hereditary angioedema due to C1-inhibitor deficiency (HAE-C1-INH) is a life-threatening, rare disease characterized by recurrent edematous attacks. In 50% of cases, the initial onset of symptoms occurs between 5 and 11 years of age. There are limited data on the emergency treatment of acute episodes in pediatric patients. Our aim was to analyze the efficacy and safety of human plasma-derived C1-INH concentrate in our pediatric patient population with HAE-C1-INH. Methods 50 pediatric patients (23 boys, 27 girls; 45 HAE type I, 5 HAE type II patients) were enrolled. The follow-up period began at the time of diagnosis and ended when the patient turned 18 years old. The indications for the use of C1-INH concentrate were upper airway oedema of any severity; moderate-to-severe abdominal edema; edema of face, neck, or lips and severe edema of the extremities and trunk. Clinical and laboratory data were entered into the Hungarian HAE Registry. Results 152 attacks out of 1392 experienced by 42 patients were treated with C1-INH concentrate (28% of attacks at home and 72% at the clinic). The distribution of C1-INH-treated attacks by location was as follows: 38% subcutaneous, 32% abdominal, 30% upper airway. In all locations, the clinical symptoms were consistently relieved by 500 IU C1-INH concentrate. An additional 500 IU dose of C1-INH concentrate was required in 4 cases only. The symptoms improved within 15 to 60 minutes of drug administration. Time to complete resolution was 24 to 48 hours in subcutaneous edema, 12 to 24 hours in abdominal attacks, and less than 12 hours when the edema involved the upper airways. No progression or recurrence of the attack was observed. Repeated administration did not reduce therapeutic efficacy of the drug. Adverse events did not occur. Transmission of viral infections (HIV, HBV, HBC, Parvo virus B19) was not detected. Comparing the first and last year of follow-up, anti-C1-INH antibodies (IgA, IgG, IgM types) did not show any

  6. Non-Ideal ELM Stability and Non-Axisymmetric Field Penetration Calculations with M3D-C1

    Science.gov (United States)

    Ferraro, N. M.; Chu, M. S.; Snyder, P. B.; Jardin, S. C.; Luo, X.

    2009-11-01

    Numerical studies of ELM stability and non-axisymmetric field penetration in diverted DIII-D and NSTX equilibria are presented, with resistive and finite Larmor radius effects included. These results are obtained with the nonlinear two-fluid code M3D-C1, which has recently been extended to allow linear non-axisymmetric calculations. Benchmarks of M3D-C1 with ideal codes ELITE and GATO show good agreement for the linear stability of peeling-ballooning modes in the ideal limit. New calculations of the resistive stability of ideally stable DIII-D equilibria are presented. M3D-C1 has also been used to calculate the linear response to non-axisymmetric external fields; these calculations are benchmarked with Surfmn and MARS-F. New numerical methods implemented in M3D-C1 are presented, including the treatment of boundary conditions with C^1 elements in a non-rectangular mesh.

  7. Overlapping ATP2C1 and ASTE1 Genes in Human Genome: Implications for SPCA1 Expression?

    Directory of Open Access Journals (Sweden)

    Massimo Micaroni

    2013-01-01

    Full Text Available The ATP2C1 gene encodes for the secretory pathway calcium (Ca2+-ATPase pump (SPCA1, which localizes along the secretory pathway, mainly in the trans-Golgi. The loss of one ATP2C1 allele causes Hailey-Hailey disease in humans but not mice. Examining differences in genomic organization between mouse and human we speculate that the overlap between ATP2C1 and ASTE1 genes only in humans could explain this different response to ATP2C1 dysregulation. We propose that ASTE1, overlapping with ATP2C1 in humans, affects alternative splicing, and potentially protein expression of the latter. If dysregulated, the composition of the SPCA1 isoform pool could diverge from the physiological status, affecting cytosolic Ca2+-signaling, and in turn perturbing cell division, leading to cell death or to neoplastic transformation.

  8. Probing scalar meson structures in $\\chi_{c1}$ decays into pseudoscalar and scalar

    CERN Document Server

    Wang, Qian; Zhao, Qiang

    2012-01-01

    We evaluate the decay branching ratios of $\\chi_{c1}\\to PS$, in a quark model parametrization scheme, where $P$ and $S$ stand for pseudoscalar and scalar meson, respectively. An interesting feature of this decay process is that the $c\\bar{c}$ annihilate via the pQCD hair-pin diagram is supposed to be dominant. Hence, this decay process should be sensitive to the quark components of the final-state light mesons, and would provide a great opportunity for testing the mixing relations among the scalar mesons, i.e. $f_0(1370)$, $f_0(1500)$ and $f_0(1710)$, by tagging the final state pseudoscalar mesons.

  9. C1 CHEMISTRY FOR THE PRODUCTION OF ULTRA-CLEAN LIQUID TRANSPORTATION FUELS AND HYDROGEN

    Energy Technology Data Exchange (ETDEWEB)

    Gerald P. Huffman

    2004-09-30

    The Consortium for Fossil Fuel Science (CFFS) is a research consortium with participants from the University of Kentucky, University of Pittsburgh, West Virginia University, University of Utah, and Auburn University. The CFFS is conducting a research program to develop C1 chemistry technology for the production of clean transportation fuel from resources such as coal and natural gas, which are more plentiful domestically than petroleum. The processes under development will convert feedstocks containing one carbon atom per molecular unit into ultra clean liquid transportation fuels (gasoline, diesel, and jet fuel) and hydrogen, which many believe will be the transportation fuel of the future. Feedstocks include synthesis gas, a mixture of carbon monoxide and hydrogen produced by coal gasification, coalbed methane, light products produced by Fischer-Tropsch (FT) synthesis, methanol, and natural gas.

  10. On trigonometric basis functions for C1 curved beam finite elements

    Science.gov (United States)

    Guimaraes, J. E. F.; Heppler, G. R.

    1992-10-01

    The formulation of a finite element model for a thin curved beam which is described by the Winkler beam model is presented. A review and discussion of the literature that pertains to this type of element is included with special attention being paid to the need to be able to recover incremental rigid body motions. Three different C1 trigonometric trial functions that allow the recovery of incremental rigid body motions are investigated. The attributes and deficiencies of the various elements are examined and discussed via several problems which have been designed to evaluate the performance of the element. The 4U4W element is shown to be the best choice of those elements considered here.

  11. The set of badly approximable vectors is strongly $C^1$ incompressible

    CERN Document Server

    Broderick, Ryan; Kleinbock, Dmitry; Reich, Asaf; Weiss, Barak

    2011-01-01

    We prove that the countable intersection of $C^1$-diffeomorphic images of certain Diophantine sets has full Hausdorff dimension. For example, we show this for the set of badly approximable vectors in $\\mathbb{R}^d$, improving earlier results of Schmidt and Dani. To prove this, inspired by ideas of McMullen, we define a new variant of Schmidt's $(\\alpha, \\beta)$-game and show that our sets are hyperplane absolute winning (HAW), which in particular implies winning in the original game. The HAW property passes automatically to games played on certain fractals, thus our sets intersect a large class of fractals in a set of positive dimension. This extends earlier results of Fishman to a more general set-up, with simpler proofs.

  12. New Technique for C1 Double-Door Laminoplasty Using Allograft Spacers and Titanium Miniplate Screw Fixation: Technical Report.

    Science.gov (United States)

    Kim, Seok Woo; Lee, Jae-Hoo; Lee, Ho-Won; Oh, Jae-Keun; Kwak, Yoon-Hae

    2016-03-01

    Although conventional C1 laminectomy is the gold standard for decompression at the atlas, it provides little space for the bone graft to fuse. The fusion area can be extended cranially up to the occipital bone, but it requires sacrificing the function of the craniocervical junction. To date, no reports have focused on surgical techniques for successful decompression and fusion without disruption of the posterior C1 arch while providing enough room for the bone graft to fuse. This study introduces a new technique for C1-C2 fusion and C1 double-door laminoplasty in patients with C1-C2 instability, canal stenosis, and cervical spondylotic myelopathy. A 66-year-old man who had undergone C1-C2 fusion at a local clinic 2 years earlier visited our hospital due to progressive myelopathy. A preoperative computed tomography (CT) scan showed the tip of the odontoid process, extending into the spinal canal. On the axial view of T2-weighted magnetic resonance images, the tip of the odontoid process significantly compressed the spinal cord on the left side. The atlantodental interval was 7 mm on radiography; however, C1-C2 instability was not evident on flexion-extension X-rays due to the previous screw fixation. The patient underwent C1-C2 decompression and fusion surgery with our new surgical technique. The segmental screws were repositioned at C1 and C2, and we performed C1 double-door laminoplasty augmented with an allograft spacer and a titanium miniplate. A marked reduction was seen at postoperative radiograph and CT scan. Neurologic symptoms were relieved dramatically after surgery without any discomfort. No complications were noted. We introduced a new surgical technique that allows bone grafting, decompression, and fusion to be performed without disruption of the posterior C1 arch in the event of C1-C2 canal stenosis combined with instability. This technique may be indicated for other conditions that cause instability and stenosis at the C1-C2 area. PMID:26689563

  13. Transcriptome profiling of whole blood cells identifies PLEK2 and C1QB in human melanoma.

    Directory of Open Access Journals (Sweden)

    Yuchun Luo

    Full Text Available Developing analytical methodologies to identify biomarkers in easily accessible body fluids is highly valuable for the early diagnosis and management of cancer patients. Peripheral whole blood is a "nucleic acid-rich" and "inflammatory cell-rich" information reservoir and represents systemic processes altered by the presence of cancer cells.We conducted transcriptome profiling of whole blood cells from melanoma patients. To overcome challenges associated with blood-based transcriptome analysis, we used a PAXgene™ tube and NuGEN Ovation™ globin reduction system. The combined use of these systems in microarray resulted in the identification of 78 unique genes differentially expressed in the blood of melanoma patients. Of these, 68 genes were further analyzed by quantitative reverse transcriptase PCR using blood samples from 45 newly diagnosed melanoma patients (stage I to IV and 50 healthy control individuals. Thirty-nine genes were verified to be differentially expressed in blood samples from melanoma patients. A stepwise logit analysis selected eighteen 2-gene signatures that distinguish melanoma from healthy controls. Of these, a 2-gene signature consisting of PLEK2 and C1QB led to the best result that correctly classified 93.3% melanoma patients and 90% healthy controls. Both genes were upregulated in blood samples of melanoma patients from all stages. Further analysis using blood fractionation showed that CD45(- and CD45(+ populations were responsible for the altered expression levels of PLEK2 and C1QB, respectively.The current study provides the first analysis of whole blood-based transcriptome biomarkers for malignant melanoma. The expression of PLEK2, the strongest gene to classify melanoma patients, in CD45(- subsets illustrates the importance of analyzing whole blood cells for biomarker studies. The study suggests that transcriptome profiling of blood cells could be used for both early detection of melanoma and monitoring of patients

  14. Prophylaxe beim hereditären Angioödem (HAE) mit C1-Inhibitormangel.

    Science.gov (United States)

    Greve, Jens; Strassen, Ulrich; Gorczyza, Marina; Dominas, Nina; Frahm, Uta-Marie; Mühlberg, Heike; Wiednig, Michaela; Zampeli, Vasiliki; Magerl, Markus

    2016-03-01

    Das hereditäre Angioödem (engl.: hereditary angioedema, HAE) ist eine seltene angeborene Erkrankung, die durch wiederkehrende Episoden subkutaner oder submuköser Ödeme charakterisiert ist. Kehlkopf-Manifestationen können lebensbedrohlich sein. In den meisten Fällen kann die Erkrankung mit einem On-Demand-Ansatz angemessen behandelt werden - in einigen Fällen ist jedoch eine Kurz- oder Langzeitprophylaxe angebracht. Attenuierte Androgene waren einmal das Standardmedikament; sie werden jedoch mit erheblichen Nebenwirkungen in Verbindung gebracht und sind in den deutschsprachigen Ländern der EU nicht mehr kommerziell erhältlich. Zurzeit werden sie von wirksameren und besser verträglichen Therapien wie C1-Esterase-Inhibitoren, dem Kallikrein-Inhibitor Ecallantid und dem B2-Rezeptorantagonisten Icatibant verdrängt, welche kürzlich auf dem Markt zugelassen wurden. Diese neuen Medikamente hatten einen erheblichen Einfluss, insbesondere auf die Indikationsstellung und das Vorgehen bei einer Langzeitprophylaxe. Nach den neuesten internationalen Konsenspapieren und unserer eigenen Erfahrung sind selbstverabreichte C1-Inhibitoren nun die erste Option bei der Langzeitprophylaxe. Die Entscheidung für eine Prophylaxe sollte nicht länger auf der Grundlage einzelner Parameter wie der Häufigkeit der Anfälle getroffen werden, sondern auf einer adäquaten allgemeinen Krankheitskontrolle, einschließlich der Lebensqualität. Zurzeit werden weitere Medikamente entwickelt, welche zu weiteren Veränderungen bei den Behandlungsalgorithmen des HAE führen könnten. PMID:26972190

  15. Solubility of alkali metal halides in the ionic liquid [C4C1im][OTf].

    Science.gov (United States)

    Kuzmina, O; Bordes, E; Schmauck, J; Hunt, P A; Hallett, J P; Welton, T

    2016-06-28

    The solubilities of the metal halides LiF, LiCl, LiBr, LiI, NaF, NaCl, NaBr, NaI, KF, KCl, KBr, KI, RbCl, CsCl, CsI, were measured at temperatures ranging from 298.15 to 378.15 K in the ionic liquid 1-butyl-3-methylimidazolium trifluoromethanesulfonate ([C4C1im][OTf]). Li(+), Na(+) and K(+) salts with anions matching the ionic liquid have also been investigated to determine how well these cations dissolve in [C4C1im][OTf]. This study compares the influence of metal cation and halide anion on the solubility of salts within this ionic liquid. The highest solubility found was for iodide salts, and the lowest solubility for the three fluoride salts. There is no outstanding difference in the solubility of salts with matching anions in comparison to halide salts. The experimental data were correlated employing several phase equilibria models, including ideal mixtures, van't Hoff, the λh (Buchowski) equation, the modified Apelblat equation, and the non-random two-liquid model (NRTL). It was found that the van't Hoff model gave the best correlation results. On the basis of the experimental data the thermodynamic dissolution parameters (ΔH, ΔS, and ΔG) were determined for the studied systems together with computed gas phase metathesis parameters. Dissolution depends on the energy difference between enthalpies of fusion and dissolution of the solute salt. This demonstrates that overcoming the lattice energy of the solid matrix is the key to the solubility of inorganic salts in ionic liquids. PMID:27264676

  16. Glucocorticoid receptor gene (NR3C1) methylation following stressful events between birth and adolescence. The TRAILS study

    Science.gov (United States)

    van der Knaap, L J; Riese, H; Hudziak, J J; Verbiest, M M P J; Verhulst, F C; Oldehinkel, A J; van Oort, F V A

    2014-01-01

    Stress early in life is a known risk factor for the development of affective disorders later in life. Epigenetic mechanisms, such as DNA methylation, may have an important role in mediating that risk. Recent epigenetic research reported on the long-term relationship between traumatic stress in childhood and DNA methylation in adulthood. In this study, we examined the impact of various types of stress (perinatal stress, stressful life events (SLEs) and traumatic youth experiences) on methylation of the glucocorticoid receptor gene (NR3C1) in the blood of a population sample of 468 adolescents (50.4% female, mean age 16.1 years). Second, we determined whether stress at different ages was associated with higher NR3C1 methylation. NR3C1 methylation rates were higher after exposure to SLEs and after exposure to traumatic youth experiences. NR3C1 methylation in adolescence was not higher after exposure to perinatal stress. Experience of SLEs in adolescence was associated with a higher NR3C1 methylation, independently of childhood SLEs. We demonstrate that not only traumatic youth experiences but also (more common) SLEs are associated with higher NR3C1 methylation. In addition, our findings underline the relevance of adolescent stress for epigenetic changes in the NR3C1 gene. PMID:24713862

  17. A hormone-responsive C1-domain-containing protein At5g17960 mediates stress response in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Ravindran Vijay Bhaskar

    Full Text Available Phytohormones play a critical role in mediating plant stress response. They employ a variety of proteins for coordinating such processes. In Arabidopsis thaliana, some members of a Cys-rich protein family known as C1-clan proteins were involved in stress response, but the actual function of the protein family is largely unknown. We studied At5g17960, a C1-clan protein member that possesses three unique C1 signature domains viz. C1_2, C1_3 and ZZ/PHD type. Additionally, we identified 72 other proteins in A. thaliana that contain all three unique signature domains. Subsequently, the 73 proteins were phylogenetically classified into IX subgroups. Promoter motif analysis of the 73 genes identified the presence of hormone-responsive and stress-responsive putative cis-regulatory elements. Furthermore, we observed that transcript levels of At5g17960 were induced in response to different hormones and stress treatments. At1g35610 and At3g13760, two other members of subgroup IV, also showed upregulation upon GA3, biotic and abiotic stress treatments. Moreover, seedlings of independent transgenic A. thaliana lines ectopically expressing or suppressing At5g17960 also showed differential regulation of several abiotic stress-responsive marker genes. Thus, our data suggest that C1-domain-containing proteins have a role to play in plant hormone-mediated stress responses, thereby assigning a putative function for the C1-clan protein family.

  18. C1-Inhibitor protects from focal brain trauma in a cortical cryolesion mice model by reducing thrombo-inflammation

    Directory of Open Access Journals (Sweden)

    Stine Mencl

    2014-09-01

    Full Text Available Traumatic brain injury (TBI induces a strong inflammatory response which includes blood-brain barrier damage, edema formation and infiltration of different immune cell subsets. More recently, microvascular thrombosis has been identified as another pathophysiological feature of TBI. The contact-kinin system represents an interface between inflammatory and thrombotic circuits and is activated in different neurological diseases. C1-Inhibitor counteracts activation of the contact-kinin system at multiple levels. We investigated the therapeutic potential of C1-Inhibitor in a model of TBI. Male and female C57BL/6 mice were subjected to cortical cryolesion and treated with C1-Inhibitor after 1 hour. Lesion volumes were assessed between day 1 and day 5 and blood-brain barrier damage, thrombus formation as well as the local inflammatory response were determined post TBI. Treatment of male mice with 15.0 IU C1-Inhibitor, but not 7.5 IU, 1 hour after cryolesion reduced lesion volumes by ~75% on day 1. This protective effect was preserved in female mice and at later stages of trauma. Mechanistically, C1-Inhibitor stabilized the blood-brain barrier and decreased the invasion of immune cells into the brain parenchyma. Moreover, C1-Inhibitor had strong antithrombotic effects. C1-Inhibitor represents a multifaceted antiinflammatory and antithrombotic compound that prevents traumatic neurodegeneration in clinically meaningful settings.

  19. 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.

  20. Inclusive and exclusive measurements of B decays to χc1 and χc2 at Belle

    Energy Technology Data Exchange (ETDEWEB)

    Bhardwaj, V.; Miyabayashi, K.; Panzenbock, E.; Trabelsi, K.; Frey, A.; Abdesselam, A.; Adachi, I.; Aihara, H.; Al Said, S.; Arinstein, K.; Asner, David M.; Atmacan, H.; Aulchenko, V.; Aushev, T.; Ayad, R.; Babu, V.; Badhrees, I.; Bahinipati, S.; Bakich, A. M.; Bala, Anu; Bansal, Vikas; Barberio, E.; Bhuyan, B.; Biswal, J.; Bobrov, A.; Bondar, A.; Bozek, A.; Bracko, Marko; Browder, Thomas E.; Cervenkov, D.; Chekelian, V.; Chen, A.; Cheon, B. G.; Chilikin, K.; Chistov, R.; Cho, K.; Chobanova, V.; Choi, S-K.; Choi, Y.; Cinabro, David A.; Dalseno, J.; Danilov, M.; Dolezal, Z.; Dutta, D.; Eidelman, S.; Farhat, H.; Fast, James E.; Ferber, T.; Frost, O.; Fulsom, Bryan G.; Gaur, Vipin; Gabyshev, N.; Ganguly, Sudeshna; Garmash, A.; Gillard, R.; Glattaur, R.; Goh, Y. M.; Goldenzweig, P.; Golob, B.; Greenwald, D.; Haba, J.; Hamer, P.; Hayasaka, K.; Hayashii, H.; He, X. H.; Hou, W. S.; Iijima, T.; Inami, K.; Ishikawa, A.; Itoh, R.; Iwasaki, Y.; Jaegle, Igal; Joffe, D.; Joo, K. K.; Julius, T.; Kato, E.; Katrenko, P.; Kawasaki, T.; Kiesling, C.; Kim, D. Y.; Kim, J. B.; Kim, K. T.; Kim, M. J.; Kim, S. H.; Kim, Y. J.; Kinoshita, Kay; Ko, Byeong Rok; Kobayashi, N.; Kodys, P.; Korpar, S.; Krizan, P.; Krokovny, Pavel; Kuhr, T.; Kumar, R.; Kumita, T.; Kuzmin, A.; Kwon , Y J; Lee, I. S.; Li, C.; Li, Y.; Li Gioi, L.; Libby, J.; Liventsev, D.; Loos, Alyssa; Lukin, P.; Masuda, M.; Matvienko, D.; Miyata, H.; Mizuk, R.; Mohanty, G. B.; Mohanty, Subhashree; Moll, A.; Moon, H K.; Mussa, R.; Nakano, E.; Nakao, M.; Nanut, T.; Natkaniec, Z.; Nayak, Minakshi; Nisar, N. K.; Nishida, S.; Ogawa, S.; Okuno, S.; Pakhlova, G.; Pal, Bilas K.; Park, C. W.; Park, H.; Pedlar, Todd; Pestotnik, R.; Petric, M.; Piilonen, Leo E.; Pulvermacher, C.; Purohit, Milind M.; Rauch, J.; Ribezl, Eva; Ritter, M.; Rostomyan, A.; Sahoo, Himansu B.; Sakai, Y.; Sandilya, Saurabh; Santelj, L.; Sanuki, T.; Sato, Y.; Savinov, Vladimir; Schneider, O.; Schnell, G.; Schwanda, C.; Seino, Y.; Semmler, D.; Senyo, K.; Seon, O.; Sevior, ME; Shebalin, V.; Shen, C. P.; Shibata, T. A.; Shiu, Jing-Ge; Shwartz, B.; Simon, F.; Singh, J. B.; Sohn, Y. S.; Sokolov, A.; Solovieva, E.; Staric, M.; Stypula, J.; Sumihama, M.; Sumiyoshi, T.; Tamponi, Umberto; Tanida, K.; Teramoto, Y.; Uchida, M.; Uehara, S.; Uglov, T.; Unno, Yuji; Uno, S.; Urquijo, P.; Usov, Y.; Van Hulse, C.; Vanhoefer, P.; Varner, Gary; Vinokurova, A.; Vorobyev, V.; Wang, C. H.; Wang, M. Z.; Wang, P.; Wang, X. L.; Watanabe, M.; Watanabe, Y.; Wehle, S.; Won, Eun Il; Yamaoka, Jared AK; Yashchenko, S.; Ye, H.; Yook, Youngmin; Yuan, C. Z.; Yusa, Y.; Zhang, Z. P.; Zhilich, V.; Zhulanov, V.; Zupanc, A.

    2016-03-29

    We report inclusive and exclusive measurements for χc1 and χc2 production in B decays. We measure B(B → χc1X)= (3.03 ± 0.05(stat) ± 0.24(syst)) × 10−3 and B(B → χc2X)= (0.70 ± 0.06(stat) ± 0.10(syst)) × 10−3 . For the first time, χc2 production in exclusive B decays in the modes B 0 → χc2π −K+ and B + → χc2π +π −K+ has been observed, along with first evidence for the B + → χc2π +K0 S decay mode. For χc1 production, we report the first observation in the B + → χc1π +π −K+, B 0 → χc1π +π −K0 S and B 0 → χc1π 0π −K+ decay modes. Using these decay modes, we observe a difference in the production mechanism of χc2 in comparison to χc1 in B decays. In addition, we report searches for X(3872) and χc1(2P) in the B + → (χc1π +π −)K+ decay 3 mode. The reported results use 772 × 106 BB events collected at the Υ(4S) resonance with the Belle detector at the KEKB asymmetric-energy e +e − collider.

  1. Peptide inhibitor of complement C1 (PIC1, a novel suppressor of classical pathway activation: mechanistic studies and clinical potential

    Directory of Open Access Journals (Sweden)

    Julia A Sharp

    2014-08-01

    Full Text Available The classical pathway of complement plays multiple physiological roles including modulating immunological effectors initiated by adaptive immune responses as well as an essential homeostatic role in the clearance of damaged self-antigens. However, dysregulated classical pathway activation is associated with antibody-initiated, inflammatory diseases processes like cold agglutinin disease (CAD, acute intravascular hemolytic transfusion reaction (AIHTR and acute/hyperacute transplantation rejection. To date, only one putative classical pathway inhibitor, C1 esterase inhibitor (C1-INH, is currently commercially available and its only approved indication is for replacement treatment in hereditary angioedema (HAE, which is predominantly a kinin pathway disease. Given the variety of disease conditions in which the classical pathway is implicated, development of therapeutics that specifically inhibit complement initiation represents a major unmet medical need. Our laboratory has identified a peptide that specifically inhibits the classical and lectin pathways of complement. In vitro studies have demonstrated that these Peptide Inhibitors of Complement C1 (PIC1 bind to the collagen-like region of the initiator molecule of the classical pathway, C1q. PIC1 binding to C1q blocks activation of the associated serine proteases (C1s-C1r-C1r-C1s and subsequent downstream complement activation. Rational design optimization of PIC1 has resulted in the generation of a highly potent derivative of fifteen amino acids. PIC1 inhibits classical pathway mediated complement activation in ABO incompatibility in vitro as well as inhibiting classical pathway activation in vivo in rats. This review will focus on the pre-clinical development of PIC1 and discuss its potential as a therapeutic in antibody-mediated classical pathway disease, specifically AIHTR.

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

    OpenAIRE

    Skoglund, Caroline

    2010-01-01

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

  3. Measurement of the $\\eta_c (1S)$ production cross-section in proton-proton collisions via the decay $\\eta_c (1S) \\rightarrow p \\bar{p}$

    CERN Document Server

    Aaij, Roel; Adeva, Bernardo; Adinolfi, Marco; Affolder, Anthony; Ajaltouni, Ziad; Akar, Simon; Albrecht, Johannes; Alessio, Federico; Alexander, Michael; Ali, Suvayu; Alkhazov, Georgy; Alvarez Cartelle, Paula; Alves Jr, Antonio Augusto; Amato, Sandra; Amerio, Silvia; Amhis, Yasmine; An, Liupan; Anderlini, Lucio; Anderson, Jonathan; Andreassen, Rolf; Andreotti, Mirco; Andrews, Jason; Appleby, Robert; Aquines Gutierrez, Osvaldo; Archilli, Flavio; Artamonov, Alexander; Artuso, Marina; Aslanides, Elie; Auriemma, Giulio; Baalouch, Marouen; Bachmann, Sebastian; Back, John; Badalov, Alexey; Baesso, Clarissa; Baldini, Wander; Barlow, Roger; Barschel, Colin; Barsuk, Sergey; Barter, William; Batozskaya, Varvara; Battista, Vincenzo; Bay, Aurelio; Beaucourt, Leo; Beddow, John; Bedeschi, Franco; Bediaga, Ignacio; Belogurov, Sergey; Belous, Konstantin; Belyaev, Ivan; Ben-Haim, Eli; Bencivenni, Giovanni; Benson, Sean; Benton, Jack; Berezhnoy, Alexander; Bernet, Roland; Bettler, Marc-Olivier; van Beuzekom, Martinus; Bien, Alexander; Bifani, Simone; Bird, Thomas; Bizzeti, Andrea; Bjørnstad, Pål Marius; Blake, Thomas; Blanc, Frédéric; Blouw, Johan; Blusk, Steven; Bocci, Valerio; Bondar, Alexander; Bondar, Nikolay; Bonivento, Walter; Borghi, Silvia; Borgia, Alessandra; Borsato, Martino; Bowcock, Themistocles; Bowen, Espen Eie; Bozzi, Concezio; Brambach, Tobias; Bressieux, Joël; Brett, David; Britsch, Markward; Britton, Thomas; Brodzicka, Jolanta; Brook, Nicholas; Brown, Henry; Bursche, Albert; Busetto, Giovanni; Buytaert, Jan; Cadeddu, Sandro; Calabrese, Roberto; Calvi, Marta; Calvo Gomez, Miriam; Campana, Pierluigi; Campora Perez, Daniel; Carbone, Angelo; Carboni, Giovanni; Cardinale, Roberta; Cardini, Alessandro; Carson, Laurence; Carvalho Akiba, Kazuyoshi; Casse, Gianluigi; Cassina, Lorenzo; Castillo Garcia, Lucia; Cattaneo, Marco; Cauet, Christophe; Cenci, Riccardo; Charles, Matthew; Charpentier, Philippe; Chefdeville, Maximilien; Chen, Shanzhen; Cheung, Shu-Faye; Chiapolini, Nicola; Chrzaszcz, Marcin; Ciba, Krzystof; Cid Vidal, Xabier; Ciezarek, Gregory; Clarke, Peter; Clemencic, Marco; Cliff, Harry; Closier, Joel; Coco, Victor; Cogan, Julien; Cogneras, Eric; Cogoni, Violetta; Cojocariu, Lucian; Collins, Paula; Comerma-Montells, Albert; Contu, Andrea; Cook, Andrew; Coombes, Matthew; Coquereau, Samuel; Corti, Gloria; Corvo, Marco; Counts, Ian; Couturier, Benjamin; Cowan, Greig; Craik, Daniel Charles; Cruz Torres, Melissa Maria; Cunliffe, Samuel; Currie, Robert; D'Ambrosio, Carmelo; Dalseno, Jeremy; David, Pascal; David, Pieter; Davis, Adam; De Bruyn, Kristof; De Capua, Stefano; De Cian, Michel; De Miranda, Jussara; De Paula, Leandro; De Silva, Weeraddana; De Simone, Patrizia; Decamp, Daniel; Deckenhoff, Mirko; Del Buono, Luigi; Déléage, Nicolas; Derkach, Denis; Deschamps, Olivier; Dettori, Francesco; Di Canto, Angelo; Dijkstra, Hans; Donleavy, Stephanie; Dordei, Francesca; Dorigo, Mirco; Dosil Suárez, Alvaro; Dossett, David; Dovbnya, Anatoliy; Dreimanis, Karlis; Dujany, Giulio; Dupertuis, Frederic; Durante, Paolo; Dzhelyadin, Rustem; Dziurda, Agnieszka; Dzyuba, Alexey; Easo, Sajan; Egede, Ulrik; Egorychev, Victor; Eidelman, Semen; Eisenhardt, Stephan; Eitschberger, Ulrich; Ekelhof, Robert; Eklund, Lars; El Rifai, Ibrahim; Graverini, Elena; Elsasser, Christian; Ely, Scott; Esen, Sevda; Evans, Hannah Mary; Evans, Timothy; Falabella, Antonio; Färber, Christian; Farinelli, Chiara; Farley, Nathanael; Farry, Stephen; Fay, Robert; Ferguson, Dianne; Fernandez Albor, Victor; Ferreira Rodrigues, Fernando; Ferro-Luzzi, Massimiliano; Filippov, Sergey; Fiore, Marco; Fiorini, Massimiliano; Firlej, Miroslaw; Fitzpatrick, Conor; Fiutowski, Tomasz; Fol, Philip; Fontana, Marianna; Fontanelli, Flavio; Forty, Roger; Francisco, Oscar; Frank, Markus; Frei, Christoph; Frosini, Maddalena; Fu, Jinlin; Furfaro, Emiliano; Gallas Torreira, Abraham; Galli, Domenico; Gallorini, Stefano; Gambetta, Silvia; Gandelman, Miriam; Gandini, Paolo; Gao, Yuanning; García Pardiñas, Julián; Garofoli, Justin; Garra Tico, Jordi; Garrido, Lluis; Gaspar, Clara; Gauld, Rhorry; Gavardi, Laura; Gavrilov, Gennadii; Geraci, Angelo; Gersabeck, Evelina; Gersabeck, Marco; Gershon, Timothy; Ghez, Philippe; Gianelle, Alessio; Gianì, Sebastiana; Gibson, Valerie; Giubega, Lavinia-Helena; Gligorov, Vladimir; Göbel, Carla; Golubkov, Dmitry; Golutvin, Andrey; Gomes, Alvaro; Gotti, Claudio; Grabalosa Gándara, Marc; Graciani Diaz, Ricardo; Granado Cardoso, Luis Alberto; Graugés, Eugeni; Graziani, Giacomo; Grecu, Alexandru; Greening, Edward; Gregson, Sam; Griffith, Peter; Grillo, Lucia; Grünberg, Oliver; Gui, Bin; Gushchin, Evgeny; Guz, Yury; Gys, Thierry; Hadjivasiliou, Christos; Haefeli, Guido; Haen, Christophe; Haines, Susan; Hall, Samuel; Hamilton, Brian; Hampson, Thomas; Han, Xiaoxue; Hansmann-Menzemer, Stephanie; Harnew, Neville; Harnew, Samuel; Harrison, Jonathan; He, Jibo; Head, Timothy; Heijne, Veerle; Hennessy, Karol; Henrard, Pierre; Henry, Louis; Hernando Morata, Jose Angel; van Herwijnen, Eric; Heß, Miriam; Hicheur, Adlène; Hill, Donal; Hoballah, Mostafa; Hombach, Christoph; Hulsbergen, Wouter; Hunt, Philip; Hussain, Nazim; Hutchcroft, David; Hynds, Daniel; Idzik, Marek; Ilten, Philip; Jacobsson, Richard; Jaeger, Andreas; Jalocha, Pawel; Jans, Eddy; Jaton, Pierre; Jawahery, Abolhassan; Jing, Fanfan; John, Malcolm; Johnson, Daniel; Jones, Christopher; Joram, Christian; Jost, Beat; Jurik, Nathan; Kaballo, Michael; Kandybei, Sergii; Kanso, Walaa; Karacson, Matthias; Karbach, Moritz; Karodia, Sarah; Kelsey, Matthew; Kenyon, Ian; Ketel, Tjeerd; Khanji, Basem; Khurewathanakul, Chitsanu; Klaver, Suzanne; Klimaszewski, Konrad; Kochebina, Olga; Kolpin, Michael; Komarov, Ilya; Koopman, Rose; Koppenburg, Patrick; Korolev, Mikhail; Kozlinskiy, Alexandr; Kravchuk, Leonid; Kreplin, Katharina; Kreps, Michal; Krocker, Georg; Krokovny, Pavel; Kruse, Florian; Kucewicz, Wojciech; Kucharczyk, Marcin; Kudryavtsev, Vasily; Kurek, Krzysztof; Kvaratskheliya, Tengiz; La Thi, Viet Nga; Lacarrere, Daniel; Lafferty, George; Lai, Adriano; Lambert, Dean; Lambert, Robert W; Lanfranchi, Gaia; Langenbruch, Christoph; Langhans, Benedikt; Latham, Thomas; Lazzeroni, Cristina; Le Gac, Renaud; van Leerdam, Jeroen; Lees, Jean-Pierre; Lefèvre, Regis; Leflat, Alexander; Lefrançois, Jacques; Leo, Sabato; Leroy, Olivier; Lesiak, Tadeusz; Leverington, Blake; Li, Yiming; Likhomanenko, Tatiana; Liles, Myfanwy; Lindner, Rolf; Linn, Christian; Lionetto, Federica; Liu, Bo; Lohn, Stefan; Longstaff, Iain; Lopes, Jose; Lopez-March, Neus; Lowdon, Peter; Lucchesi, Donatella; Luo, Haofei; Lupato, Anna; Luppi, Eleonora; Lupton, Oliver; Machefert, Frederic; Machikhiliyan, Irina V; Maciuc, Florin; Maev, Oleg; Malde, Sneha; Malinin, Alexander; Manca, Giulia; Mancinelli, Giampiero; Mapelli, Alessandro; Maratas, Jan; Marchand, Jean François; Marconi, Umberto; Marin Benito, Carla; Marino, Pietro; Märki, Raphael; Marks, Jörg; Martellotti, Giuseppe; Martens, Aurelien; Martín Sánchez, Alexandra; Martinelli, Maurizio; Martinez Santos, Diego; Martinez Vidal, Fernando; Martins Tostes, Danielle; Massafferri, André; Matev, Rosen; Mathe, Zoltan; Matteuzzi, Clara; Mazurov, Alexander; McCann, Michael; McCarthy, James; McNab, Andrew; McNulty, Ronan; McSkelly, Ben; Meadows, Brian; Meier, Frank; Meissner, Marco; Merk, Marcel; Milanes, Diego Alejandro; Minard, Marie-Noelle; Moggi, Niccolò; Molina Rodriguez, Josue; Monteil, Stephane; Morandin, Mauro; Morawski, Piotr; Mordà, Alessandro; Morello, Michael Joseph; Moron, Jakub; Morris, Adam Benjamin; Mountain, Raymond; Muheim, Franz; Müller, Katharina; Mussini, Manuel; Muster, Bastien; Naik, Paras; Nakada, Tatsuya; Nandakumar, Raja; Nasteva, Irina; Needham, Matthew; Neri, Nicola; Neubert, Sebastian; Neufeld, Niko; Neuner, Max; Nguyen, Anh Duc; Nguyen, Thi-Dung; Nguyen-Mau, Chung; Nicol, Michelle; Niess, Valentin; Niet, Ramon; Nikitin, Nikolay; Nikodem, Thomas; Novoselov, Alexey; O'Hanlon, Daniel Patrick; Oblakowska-Mucha, Agnieszka; Obraztsov, Vladimir; Oggero, Serena; Ogilvy, Stephen; Okhrimenko, Oleksandr; Oldeman, Rudolf; Onderwater, Gerco; Orlandea, Marius; Otalora Goicochea, Juan Martin; Owen, Patrick; Oyanguren, Maria Arantza; Pal, Bilas Kanti; Palano, Antimo; Palombo, Fernando; Palutan, Matteo; Panman, Jacob; Papanestis, Antonios; Pappagallo, Marco; Pappalardo, Luciano; Parkes, Christopher; Parkinson, Christopher John; Passaleva, Giovanni; Patel, Girish; Patel, Mitesh; Patrignani, Claudia; Pazos Alvarez, Antonio; Pearce, Alex; Pellegrino, Antonio; Pepe Altarelli, Monica; Perazzini, Stefano; Perez Trigo, Eliseo; Perret, Pascal; Perrin-Terrin, Mathieu; Pescatore, Luca; Pesen, Erhan; Petridis, Konstantin; Petrolini, Alessandro; Picatoste Olloqui, Eduardo; Pietrzyk, Boleslaw; Pilař, Tomas; Pinci, Davide; Pistone, Alessandro; Playfer, Stephen; Plo Casasus, Maximo; Polci, Francesco; Poluektov, Anton; Polycarpo, Erica; Popov, Alexander; Popov, Dmitry; Popovici, Bogdan; Potterat, Cédric; Price, Eugenia; Price, Joseph David; Prisciandaro, Jessica; Pritchard, Adrian; Prouve, Claire; Pugatch, Valery; Puig Navarro, Albert; Punzi, Giovanni; Qian, Wenbin; Rachwal, Bartolomiej; Rademacker, Jonas; Rakotomiaramanana, Barinjaka; Rama, Matteo; Rangel, Murilo; Raniuk, Iurii; Rauschmayr, Nathalie; Raven, Gerhard; Redi, Federico; Reichert, Stefanie; Reid, Matthew; dos Reis, Alberto; Ricciardi, Stefania; Richards, Sophie; Rihl, Mariana; Rinnert, Kurt; Rives Molina, Vincente; Robbe, Patrick; Rodrigues, Ana Barbara; Rodrigues, Eduardo; Rodriguez Perez, Pablo; Roiser, Stefan; Romanovsky, Vladimir; Romero Vidal, Antonio; Rotondo, Marcello; Rouvinet, Julien; Ruf, Thomas; Ruiz, Hugo; Ruiz Valls, Pablo; Saborido Silva, Juan Jose; Sagidova, Naylya; Sail, Paul; Saitta, Biagio; Salustino Guimaraes, Valdir; Sanchez Mayordomo, Carlos; Sanmartin Sedes, Brais; Santacesaria, Roberta; Santamarina Rios, Cibran; Santovetti, Emanuele; Sarti, Alessio; Satriano, Celestina; Satta, Alessia; Saunders, Daniel Martin; Savrie, Mauro; Savrina, Darya; Schiller, Manuel; Schindler, Heinrich; Schlupp, Maximilian; Schmelling, Michael; Schmidt, Burkhard; Schneider, Olivier; Schopper, Andreas; Schune, Marie Helene; Schwemmer, Rainer; Sciascia, Barbara; Sciubba, Adalberto; Seco, Marcos; Semennikov, Alexander; Sepp, Indrek; Serra, Nicola; Serrano, Justine; Sestini, Lorenzo; Seyfert, Paul; Shapkin, Mikhail; Shapoval, Illya; Shcheglov, Yury; Shears, Tara; Shekhtman, Lev; Shevchenko, Vladimir; Shires, Alexander; Silva Coutinho, Rafael; Simi, Gabriele; Sirendi, Marek; Skidmore, Nicola; Skwarnicki, Tomasz; Smith, Anthony; Smith, Edmund; Smith, Eluned; Smith, Jackson; Smith, Mark; Snoek, Hella; Sokoloff, Michael; Soler, Paul; Soomro, Fatima; Souza, Daniel; Souza De Paula, Bruno; Spaan, Bernhard; Sparkes, Ailsa; Spradlin, Patrick; Sridharan, Srikanth; Stagni, Federico; Stahl, Marian; Stahl, Sascha; Steinkamp, Olaf; Stenyakin, Oleg; Stevenson, Scott; Stoica, Sabin; Stone, Sheldon; Storaci, Barbara; Stracka, Simone; Straticiuc, Mihai; Straumann, Ulrich; Stroili, Roberto; Subbiah, Vijay Kartik; Sun, Liang; Sutcliffe, William; Swientek, Krzysztof; Swientek, Stefan; Syropoulos, Vasileios; Szczekowski, Marek; Szczypka, Paul; Szilard, Daniela; Szumlak, Tomasz; T'Jampens, Stephane; Teklishyn, Maksym; Tellarini, Giulia; Teubert, Frederic; Thomas, Christopher; Thomas, Eric; van Tilburg, Jeroen; Tisserand, Vincent; Tobin, Mark; Tolk, Siim; Tomassetti, Luca; Tonelli, Diego; Topp-Joergensen, Stig; Torr, Nicholas; Tournefier, Edwige; Tourneur, Stephane; Tran, Minh Tâm; Tresch, Marco; Tsaregorodtsev, Andrei; Tsopelas, Panagiotis; Tuning, Niels; Ubeda Garcia, Mario; Ukleja, Artur; Ustyuzhanin, Andrey; Uwer, Ulrich; Vacca, Claudia; Vagnoni, Vincenzo; Valenti, Giovanni; Vallier, Alexis; Vazquez Gomez, Ricardo; Vazquez Regueiro, Pablo; Vázquez Sierra, Carlos; Vecchi, Stefania; Velthuis, Jaap; Veltri, Michele; Veneziano, Giovanni; Vesterinen, Mika; Viaud, Benoit; Vieira, Daniel; Vieites Diaz, Maria; Vilasis-Cardona, Xavier; Vollhardt, Achim; Volyanskyy, Dmytro; Voong, David; Vorobyev, Alexey; Vorobyev, Vitaly; Voß, Christian; Voss, Helge; de Vries, Jacco; Waldi, Roland; Wallace, Charlotte; Wallace, Ronan; Walsh, John; Wandernoth, Sebastian; Wang, Jianchun; Ward, David; Watson, Nigel; Websdale, David; Whitehead, Mark; Wicht, Jean; Wiedner, Dirk; Wilkinson, Guy; Williams, Matthew; Williams, Mike; Wilschut, Hans; Wilson, Fergus; Wimberley, Jack; Wishahi, Julian; Wislicki, Wojciech; Witek, Mariusz; Wormser, Guy; Wotton, Stephen; Wright, Simon; Wyllie, Kenneth; Xie, Yuehong; Xing, Zhou; Xu, Zhirui; Yang, Zhenwei; Yuan, Xuhao; Yushchenko, Oleg; Zangoli, Maria; Zavertyaev, Mikhail; Zhang, Liming; Zhang, Wen Chao; Zhang, Yanxi; Zhelezov, Alexey; Zhokhov, Anatoly; Zhong, Liang; Zvyagin, Alexander

    2015-01-01

    The production of the $\\eta_c (1S)$ state in proton-proton collisions is probed via its decay to the $p \\bar{p}$ final state with the LHCb detector, in the rapidity range $2.0 6.5$ GeV/c. The cross-section for prompt production of $\\eta_c (1S)$ mesons relative to the prompt $J/\\psi$ cross-section is measured, for the first time, to be $\\sigma_{\\eta_c (1S)}/\\sigma_{J/\\psi} = 1.74 \\pm 0.29 \\pm 0.28 \\pm 0.18 _{B}$ at a centre-of-mass energy $\\sqrt{s} = 7$ TeV using data corresponding to an integrated luminosity of 0.7 fb$^{-1}$, and $\\sigma_{\\eta_c (1S)}/\\sigma_{J/\\psi} = 1.60 \\pm 0.29 \\pm 0.25 \\pm 0.17 _{B}$ at $\\sqrt{s} = 8$ TeV using 2.0 fb$^{-1}$. The uncertainties quoted are, in order, statistical, systematic, and that on the ratio of branching fractions of the $\\eta_c (1S)$ and $J/\\psi$ decays to the $p \\bar{p}$ final state. In addition, the inclusive branching fraction of $b$-hadron decays into $\\eta_c (1S)$ mesons is measured, for the first time, to be $B ( b \\rightarrow \\eta_c X ) = (4.88 \\pm 0.64 \\pm ...

  4. Search for the Z_1(4050)^+ and Z_2(4250)^+ States in bar B^0 to chi_{c1} K^- pi^+ and B^+ to chi_{c1} K^0_S pi^+

    Energy Technology Data Exchange (ETDEWEB)

    Lees, J.P.; Poireau, V.; Tisserand, V.; /Annecy, LAPP; Garra Tico, J.; Grauges, E.; /Barcelona U., ECM; Martinelli, M.; /INFN, Bari /Bari U.; Milanes, D.A.; /INFN, Bari; Palano, A.; Pappagallo, M.; /INFN, Bari /Bari U.; Eigen, G.; Stugu, B.; /Bergen U.; Brown, D.N.; Kerth, L.T.; Kolomensky, Yu.G.; Lynch, G.; /UC, Berkeley; Koch, H.; Schroeder, T.; /Ruhr U., Bochum; Asgeirsson, D.J.; Hearty, C.; Mattison, T.S.; McKenna, J.A.; /British Columbia U. /Brunel U. /Novosibirsk, IYF /UC, Irvine /UC, Riverside /UC, Santa Barbara /UC, Santa Cruz /Caltech /Cincinnati U. /Colorado U. /Colorado State U. /Dortmund U. /Dresden, Tech. U. /Ecole Polytechnique /Edinburgh U. /INFN, Ferrara /Ferrara U. /INFN, Ferrara /Ferrara U. /INFN, Ferrara /Frascati /INFN, Genoa /Genoa U. /INFN, Genoa /INFN, Genoa /Genoa U. /INFN, Genoa /Indian Inst. Tech., Guwahati /Harvard U. /Harvey Mudd Coll. /Heidelberg U. /Humboldt U., Berlin /Imperial Coll., London /Iowa State U. /Iowa State U. /Johns Hopkins U. /Paris U., VI-VII /LLNL, Livermore /Liverpool U. /Queen Mary, U. of London /Royal Holloway, U. of London /Royal Holloway, U. of London /Louisville U. /Mainz U., Inst. Kernphys. /Manchester U. /Maryland U. /Massachusetts U., Amherst /MIT /McGill U. /INFN, Milan /Milan U. /Mississippi U. /Montreal U. /INFN, Naples /Naples U. /NIKHEF, Amsterdam /NIKHEF, Amsterdam /Notre Dame U. /Ohio State U. /Oregon U. /INFN, Padua /Padua U. /INFN, Padua /INFN, Padua /Padua U. /Paris U., VI-VII /INFN, Perugia /Perugia U. /INFN, Pisa /Pisa U. /INFN, Pisa /Pisa, Scuola Normale Superiore /INFN, Pisa /Pisa U. /INFN, Pisa /INFN, Pisa /Pisa U. /INFN, Pisa /Princeton U. /INFN, Rome /INFN, Rome /Rome U. /INFN, Rome /INFN, Rome /Rome U. /INFN, Rome /Rostock U. /Rutherford /DAPNIA, Saclay /SLAC /South Carolina U. /Southern Methodist U. /Stanford U., Phys. Dept. /SUNY, Albany /Tel Aviv U. /Tennessee U. /Texas Nuclear Corp., Austin /Texas U., Dallas /INFN, Turin /Turin U. /INFN, Trieste /Trieste U. /Valencia U. /Victoria U. /Warwick U. /Wisconsin U., Madison

    2012-04-10

    We search for the Z{sub 1}(4050){sup +} and Z{sub 2}(4250){sup +} states, reported by the Belle Collaboration, decaying to {chi}{sub c1}{pi}{sup +} in the decays {bar B}{sup 0} {yields} {chi}{sub c1}K{sup -}{pi}{sup +} and B{sup +} {yields} {chi}{sub c1}K{sub S}{sup 0}{pi}{sup +} where {chi}{sub c1} {yields} J/{psi}{gamma}. The data were collected with the BABAR detector at the SLAC PEP-II asymmetric-energy e{sup +}e{sup -} collider operating at center-of-mass energy 10.58 GeV, and correspond to an integrated luminosity of 429 fb{sup -1}. In this analysis, we model the background-subtracted, efficiency-corrected {chi}{sub c1}{pi}{sup +} mass distribution using the K{pi} mass distribution and the corresponding normalized K{pi} Legendre polynomial moments, and then test the need for the inclusion of resonant structures in the description of the {chi}{sub c1}{pi}{sup +} mass distribution. No evidence is found for the Z{sub 1}(4050){sup +} and Z{sub 2}(4250){sup +} resonances, and 90% confidence level upper limits on the branching fractions are reported for the corresponding B-meson decay modes.

  5. C1 Chemistry for the Production of Ultra-Clean Liquid Transportation Fuels and Hydrogen

    Energy Technology Data Exchange (ETDEWEB)

    Gerald P. Huffman

    2006-03-30

    Professors and graduate students from five universities--the University of Kentucky, University of Pittsburgh, University of Utah, West Virginia University, and Auburn University--are collaborating in a research program to develop C1 chemistry processes to produce ultra-clean liquid transportation fuels and hydrogen, the zero-emissions transportation fuel of the future. The feedstocks contain one carbon atom per molecular unit. They include synthesis gas (syngas), a mixture of carbon monoxide and hydrogen produced by coal gasification or reforming of natural gas, methane, methanol, carbon dioxide, and carbon monoxide. An important objective is to develop C1 technology for the production of liquid transportation fuel and hydrogen from domestically plentiful resources such as coal, coalbed methane, and hydrocarbon gases and liquids produced from coal. An Advisory Board with representatives from Chevron-Texaco, Eastman Chemical, Conoco-Phillips, the Air Force Research Laboratory, the U.S. Army National Automotive Center, and Tier Associates provides guidance on the practicality of the research. The current report summarizes the results obtained in this program during the period October 1, 2002 through March 31, 2006. The results are presented in detailed reports on 16 research projects headed by professors at each of the five CFFS Universities and an Executive Summary. Some of the highlights from these results are: (1) Small ({approx}1%) additions of acetylene or other alkynes to the Fischer-Tropsch (F-T) reaction increases its yield, causes chain initiation, and promotes oxygenate formation. (2) The addition of Mo to Fe-Cu-K/AC F-T catalysts improves catalyst lifetime and activity. (3) The use of gas phase deposition to place highly dispersed metal catalysts on silica or ceria aerogels offers promise for both the F-T and the water-gas shift WGS reactions. (4) Improved activity and selectivity are exhibited by Co F-T catalysts in supercritical hexane. (5) Binary Fe

  6. C1 CHEMISTRY FOR THE PRODUCTION OF ULTRA-CLEAN LIQUID TRANSPORTATION FUELS AND HYDROGEN

    Energy Technology Data Exchange (ETDEWEB)

    Gerald P. Huffman

    2003-09-30

    The Consortium for Fossil Fuel Science (CFFS) is a research consortium with participants from the University of Kentucky, University of Pittsburgh, University of Utah, West Virginia University, and Auburn University. The CFFS is conducting a research program to develop C1 chemistry technology for the production of clean transportation fuel from resources such as coal and natural gas, which are more plentiful domestically than petroleum. The processes under development will convert feedstocks containing one carbon atom per molecular unit into ultra clean liquid transportation fuels (gasoline, diesel, and jet fuel) and hydrogen, which many believe will be the transportation fuel of the future. These feedstocks include synthesis gas, a mixture of carbon monoxide and hydrogen produced by coal gasification or reforming of natural gas, methane, methanol, carbon dioxide, and carbon monoxide. Some highlights of the results obtained during the first year of the current research contract are summarized as: (1) Terminal alkynes are an effective chain initiator for Fischer-Tropsch (FT) reactions, producing normal paraffins with C numbers {ge} to that of the added alkyne. (2) Significant improvement in the product distribution towards heavier hydrocarbons (C{sub 5} to C{sub 19}) was achieved in supercritical fluid (SCF) FT reactions compared to that of gas-phase reactions. (3) Xerogel and aerogel silica supported cobalt catalysts were successfully employed for FT synthesis. Selectivity for diesel range products increased with increasing Co content. (4) Silicoaluminophosphate (SAPO) molecular sieve catalysts have been developed for methanol to olefin conversion, producing value-added products such as ethylene and propylene. (5) Hybrid Pt-promoted tungstated and sulfated zirconia catalysts are very effective in cracking n-C{sub 36} to jet and diesel fuel; these catalysts will be tested for cracking of FT wax. (6) Methane, ethane, and propane are readily decomposed to pure

  7. Search for Al-26 effects in the Allende FUN inclusion C1. [Fractionation and Unknown Nuclear anomalies

    Science.gov (United States)

    Esat, T. M.; Lee, T.; Papanastassiou, D. A.; Wasserburg, G. J.

    1978-01-01

    The Mg isotopic composition of major and minor mineral phases in the Allende inclusion C1 is reported. The results are analyzed in order to establish whether the Mg isotopic composition is the same in different phases and whether Al-26 is present in a sample which exhibited fractionation and unknown nuclear (FUN) effects on other elements. It is found that a small Mg-26 excess exists in C1 and is correlated with the Al-27/Mg-24 ratio, indicating that Al-26 was present in C1 together with the more general nuclear anomalies. The results also reveal that isotopic homogeneity of Mg in Mg-rich phases in C1 is evident in both bulk samples and single microscopic crystals.

  8. aThe dyslexia candidate gene DYX1C1 is a potential marker of poor survival in breast cancer

    International Nuclear Information System (INIS)

    The dyslexia candidate gene, DYX1C1, shown to regulate and interact with estrogen receptors and involved in the regulation of neuronal migration, has recently been proposed as a putative cancer biomarker. This study was undertaken to assess the prognostic value and therapy-predictive potential of DYX1C1 mRNA and protein expression in breast cancer. DYX1C1 mRNA expression was assessed at the mRNA level in three independent population-derived patient cohorts. An association to estrogen/progesterone receptor status, Elston grade, gene expression subtype and lymph node status was analyzed within these cohorts. DYX1C1 protein expression was examined using immunohistochemistry in cancer and normal breast tissue. The statistical analyses were performed using the non-parametric Wilcoxon rank-sum test, ANOVA, Fisher's exact test and a multivariate proportional hazard (Cox) model. DYX1C1 mRNA is significantly more highly expressed in tumors that have been classified as estrogen receptor α and progesterone receptor-positive. The expression of DYX1C1 among the molecular subtypes shows the lowest median expression within the basal type tumors, which are considered to have the worst prognosis. The expression of DYX1C1 is significantly lower in tumors graded as Elston grade 3 compared with grades 1 and 2. DYX1C1 protein is expressed in 88% of tumors and in all 10 normal breast tissues examined. Positive protein expression was significantly correlated to overall survival (Hazard ratio 3.44 [CI 1.84-6.42]) of the patients but not to any of the variables linked with mRNA expression. We show that the expression of DYX1C1 in breast cancer is associated with several clinicopathological parameters and that loss of DYX1C1 correlates with a more aggressive disease, in turn indicating that DYX1C1 is a potential prognostic biomarker in breast cancer

  9. [Failed compression osteosynthesis of the dens axis treated by anterior C1-C2 transarticular stabilisation. Case report].

    Science.gov (United States)

    Kočiš, J; Kelbl, M

    2011-01-01

    We describe the case of an 80-year-old female patient who had undergone anterior C1-C2 transarticular stabilisation and was subsequently treated by the triple-screw method for failed compression osteosynthesis of a AO type III dens axis fracture. Key words: dens axis, upper cervical spine fracture, eldery, triple screw technique, anterior transarticular C1-C2 stabilisation. PMID:21729645

  10. GLOBAL C1 SOLUTION TO THE INITIAL-BOUNDARY VALUE PROBLEM FOR DIAGONAL HYPERBOLIC SYSTEMS WITH LINEARLY DEGENERATE CHARACTERISTICS

    Institute of Scientific and Technical Information of China (English)

    Li Ta-tsien(李大潜); Peng Yue-Jun

    2003-01-01

    Abstract We prove that the C0 boundedness of solution impliesthe global existence and uniqueness of C1 solution to the initial-boundary value problem for linearly degenerate quasilinear hyperbolic systems of diagonal form with nonlinear boundary conditions. Thus, if the C1 solution to the initial-boundary value problem blows up in a finite time, then the solution itself must tend to the infinity at the starting point of singularity.

  11. Complement protein C1q directs macrophage polarization and limits inflammasome activity during the uptake of apoptotic cells

    OpenAIRE

    Benoit, Marie E; Clarke, Elizabeth V.; Morgado, Pedro; Fraser, Deborah A.; Tenner, Andrea J.

    2012-01-01

    Deficiency in C1q, the recognition component of the classical complement cascade and a pattern recognition receptor involved in apoptotic cell clearance, leads to lupus-like auto-immune diseases characterized by auto-antibodies to self proteins and aberrant innate immune cell activation likely due to impaired clearance of apoptotic cells. Here, we developed an autologous system using primary human lymphocytes and monocyte-derived macrophages (HMDMs) to characterize the effect of C1q on macrop...

  12. Correlation of Serum Soluble Interleukin-7 Receptor and Anti-C1q Antibody in Patients with Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Shuhong Chi

    2016-01-01

    Full Text Available Background. Serum concentrations of soluble interleukin-7 receptor (sIL-7R and anti-C1q antibody have recently been identified as unique serological markers for lupus nephritis (LN in patients with systemic lupus erythematosus (SLE. In this study, we evaluated the correlation of serum sIL-7R and anti-C1q in SLE patients. Methods. Sera from 134 patients with SLE and 84 healthy cohorts were tested for levels of sIL-7R and anti-C1q antibodies in terms of ELISA. Correlations of the sIL-7R and anti-C1q autoantibodies were evaluated. Results. The serum concentrations of sIL-7R and anti-C1q antibodies were significantly higher in SLE patients and LN patients in comparison with healthy individuals/controls and SLE patients with non-LN, respectively. In addition, both sIL-7R and anti-C1q concentrations were found to significantly correlate with the SLE disease activity as evaluated by SLEDAI scores. Interestingly, the serum sIL-7R concentration was strongly correlated with the level of anti-C1q antibodies (r=0.2871, p=0.0008 but not statistically correlated with other serological markers, including the anti-dsDNA and complements C3 and C4 concentrations in SLE patients. Conclusion. Both serum sIL-7R and anti-C1q antibodies were strongly associated with disease activity and LN in SLE patients, suggesting that they may be reliable serological markers for identification of SLE patients with active diseases and LN.

  13. The prophylactic use of C1 inhibitor in hereditary angioedema patients undergoing invasive surgical procedures: a retrospective study

    OpenAIRE

    Gavigan, Geneviève; Yang, William H; Santucci, Stephanie; Harrison, Rachel; Karsh, Jacob

    2014-01-01

    Background Hereditary Angioedema (HAE) is a rare autosomal dominant condition characterized by episodic angioedema, which may be triggered by invasive procedures and surgery. C1 inhibitor (C1 INH) was approved in the United States and Canada in 2009 and 2010, respectively, for the treatment of acute attacks. Most recently in April 2013, it was approved in Europe for short-term prophylaxis (STP), prior to medical, dental, or surgical procedures, to prevent HAE attacks in both children and adul...

  14. Vertical ozone distribution characteristics deduced from 44,000 re-evaluated Umkehr profiles (1957-2000)

    Science.gov (United States)

    Bojkov, R. D.; Kosmidis, E.; DeLuisi, J. J.; Petropavlovskikh, I.; Fioletov, V. E.; Godin, S.; Zerefos, C.

    maximum. The deduced trends above 33km confirm a strong ozone decline since the mid-1970s of over 5% per decade without significant seasonal differences. In the mid-latitude stations, the decline in the 15-24km layer is nearly twice as strong in the winter-spring season but much smaller in the summer and fall. The effect of including 1998 and 1999 years with relatively high total ozone data reduces the overall-declining trend. The trends estimated from alg-99 retrievals are statistically not significantly different from those in WMO 1998a; however, they are stronger by about 1% per decade in the lower stratosphere and thus closer to the estimates by sondes. Comparisons of the integrated ozone loss from the Umkehr measurements with the total ozone changes for the same periods at stations with good records show complete concurrence. The altitude and latitude appearances of the long-term geophysical signals like solar (1-2%) and QBO (2-7%) are investigated.

  15. Optical Spectral Observations of a Flickering White-Light Kernel in a C1 Solar Flare

    CERN Document Server

    Kowalski, Adam F; Fletcher, Lyndsay

    2014-01-01

    We analyze optical spectra of a two-ribbon, long duration C1.1 flare that occurred on 18 Aug 2011 within AR 11271 (SOL2011-08-18T15:15). The impulsive phase of the flare was observed with a comprehensive set of space-borne and ground-based instruments, which provide a range of unique diagnostics of the lower flaring atmosphere. Here we report the detection of enhanced continuum emission, observed in low-resolution spectra from 3600 \\AA\\ to 4550 \\AA\\ acquired with the Horizontal Spectrograph at the Dunn Solar Telescope. A small, $\\le$0''.5 ($10^{15}$ cm$^2$) penumbral/umbral kernel brightens repeatedly in the optical continuum and chromospheric emission lines, similar to the temporal characteristics of the hard X-ray variation as detected by the Gamma-ray Burst Monitor (GBM) on the Fermi spacecraft. Radiative-hydrodynamic flare models that employ a nonthermal electron beam energy flux high enough to produce the optical contrast in our flare spectra would predict a large Balmer jump in emission, indicative of h...

  16. Necroptosis in Niemann–Pick disease, type C1: a potential therapeutic target

    Science.gov (United States)

    Cougnoux, A; Cluzeau, C; Mitra, S; Li, R; Williams, I; Burkert, K; Xu, X; Wassif, C A; Zheng, W; Porter, F D

    2016-01-01

    Niemann–Pick disease, type C1 (NPC1) is a neurodegenerative, lysosomal storage disorder due to mutation of the NPC1 gene. The NPC1 phenotype is characterized by progressive neuronal dysfunction, including cerebellar ataxia and dementia. There is histological evidence of neuroinflammation and progressive neuronal loss, with cerebellar Purkinje cells particularly vulnerable to loss of NPC1 function. Necroptosis was evaluated as a mechanism of neuronal loss. Receptor-interacting protein kinase 1 (RIP1) and RIP3 are key components of the necrosomal complex that regulates necroptotic cell death. We report increased expression of RIP1 and RIP3 in NPC1 fibroblasts, NPC1 iPS cell-derived neuronal precursors, and in cerebellar tissue from both NPC1 mice and patients. Our data suggest a positive correlation between NPC1 neurological disease severity and assembly of the necrosome complex. Furthermore, we demonstrate that pharmacological inhibition of RIP1 decreases cell death both in vitro and in vivo. Treatment of Npc1-mutant mice with necrostatin-1, an allosteric inhibitor of RIP1, significantly delayed cerebellar Purkinje cell loss, progression of neurological symptoms, and death. Collectively, our data identified necroptosis as a key component of the molecular network that contributes to neuronal loss in NPC1 and establish that inhibition of necroptosis is a potential therapeutic intervention. PMID:26986514

  17. Impaired Autophagy in the Lipid-Storage Disorder Niemann-Pick Type C1 Disease

    Directory of Open Access Journals (Sweden)

    Sovan Sarkar

    2013-12-01

    Full Text Available Autophagy dysfunction has been implicated in misfolded protein accumulation and cellular toxicity in several diseases. Whether alterations in autophagy also contribute to the pathology of lipid-storage disorders is not clear. Here, we show defective autophagy in Niemann-Pick type C1 (NPC1 disease associated with cholesterol accumulation, where the maturation of autophagosomes is impaired because of defective amphisome formation caused by failure in SNARE machinery, whereas the lysosomal proteolytic function remains unaffected. Expression of functional NPC1 protein rescues this defect. Inhibition of autophagy also causes cholesterol accumulation. Compromised autophagy was seen in disease-affected organs of Npc1 mutant mice. Of potential therapeutic relevance is that HP-β-cyclodextrin, which is used for cholesterol-depletion treatment, impedes autophagy, whereas stimulating autophagy restores its function independent of amphisome formation. Our data suggest that a low dose of HP-β-cyclodextrin that does not perturb autophagy, coupled with an autophagy inducer, may provide a rational treatment strategy for NPC1 disease.

  18. Necroptosis in Niemann-Pick disease, type C1: a potential therapeutic target.

    Science.gov (United States)

    Cougnoux, A; Cluzeau, C; Mitra, S; Li, R; Williams, I; Burkert, K; Xu, X; Wassif, C A; Zheng, W; Porter, F D

    2016-01-01

    Niemann-Pick disease, type C1 (NPC1) is a neurodegenerative, lysosomal storage disorder due to mutation of the NPC1 gene. The NPC1 phenotype is characterized by progressive neuronal dysfunction, including cerebellar ataxia and dementia. There is histological evidence of neuroinflammation and progressive neuronal loss, with cerebellar Purkinje cells particularly vulnerable to loss of NPC1 function. Necroptosis was evaluated as a mechanism of neuronal loss. Receptor-interacting protein kinase 1 (RIP1) and RIP3 are key components of the necrosomal complex that regulates necroptotic cell death. We report increased expression of RIP1 and RIP3 in NPC1 fibroblasts, NPC1 iPS cell-derived neuronal precursors, and in cerebellar tissue from both NPC1 mice and patients. Our data suggest a positive correlation between NPC1 neurological disease severity and assembly of the necrosome complex. Furthermore, we demonstrate that pharmacological inhibition of RIP1 decreases cell death both in vitro and in vivo. Treatment of Npc1-mutant mice with necrostatin-1, an allosteric inhibitor of RIP1, significantly delayed cerebellar Purkinje cell loss, progression of neurological symptoms, and death. Collectively, our data identified necroptosis as a key component of the molecular network that contributes to neuronal loss in NPC1 and establish that inhibition of necroptosis is a potential therapeutic intervention. PMID:26986514

  19. Crossing the c=1 barrier in 2D Lorentzian quantum gravity

    Science.gov (United States)

    Ambjørn, J.; Anagnostopoulos, K.; Loll, R.

    2000-02-01

    In an extension of earlier work we investigate the behavior of two-dimensional (2D) Lorentzian quantum gravity under coupling to a conformal field theory with c>1. This is done by analyzing numerically a system of eight Ising models (corresponding to c=4) coupled to dynamically triangulated Lorentzian geometries. It is known that a single Ising model couples weakly to Lorentzian quantum gravity, in the sense that the Hausdorff dimension of the ensemble of two-geometries is two (as in pure Lorentzian quantum gravity) and the matter behavior is governed by the Onsager exponents. By increasing the amount of matter to eight Ising models, we find that the geometry of the combined system has undergone a phase transition. The new phase is characterized by an anomalous scaling of spatial length relative to proper time at large distances, and as a consequence the Hausdorff dimension is now three. In spite of this qualitative change in the geometric sector, and a very strong interaction between matter and geometry, the critical exponents of the Ising model retain their Onsager values. This provides evidence for the conjecture that the KPZ values of the critical exponents in 2D Euclidean quantum gravity are entirely due to the presence of baby universes. Lastly, we summarize the lessons learned so far from 2D Lorentzian quantum gravity.

  20. Ebola Viral Glycoprotein Bound to Its Endosomal Receptor Niemann-Pick C1.

    Science.gov (United States)

    Wang, Han; Shi, Yi; Song, Jian; Qi, Jianxun; Lu, Guangwen; Yan, Jinghua; Gao, George F

    2016-01-14

    Filoviruses, including Ebola and Marburg, cause fatal hemorrhagic fever in humans and primates. Understanding how these viruses enter host cells could help to develop effective therapeutics. An endosomal protein, Niemann-Pick C1 (NPC1), has been identified as a necessary entry receptor for this process, and priming of the viral glycoprotein (GP) to a fusion-competent state is a prerequisite for NPC1 binding. Here, we have determined the crystal structure of the primed GP (GPcl) of Ebola virus bound to domain C of NPC1 (NPC1-C) at a resolution of 2.3 Å. NPC1-C utilizes two protruding loops to engage a hydrophobic cavity on head of GPcl. Upon enzymatic cleavage and NPC1-C binding, conformational change in the GPcl further affects the state of the internal fusion loop, triggering membrane fusion. Our data therefore provide structural insights into filovirus entry in the late endosome and the molecular basis for design of therapeutic inhibitors of viral entry. PMID:26771495

  1. Mineralogical characterization of ambient fine/ultrafine particles emitted from Xuanwei C1 coal combustion

    Science.gov (United States)

    Lu, Senlin; Hao, Xiaojie; Liu, Dingyu; Wang, Qiangxiang; Zhang, Wenchao; Liu, Pinwei; Zhang, Rongci; Yu, Shang; Pan, Ruiqi; Wu, Minghong; Yonemochi, Shinich; Wang, Qingyue

    2016-03-01

    Nano-quartz in Xuanwei coal, the uppermost Permian (C1) coal deposited in the northwest of Yuanan, China, has been regarded as one of factors which caused high lung cancer incidence in the local residents. However, mineralogical characterization of the fine/ultrafine particles emitted from Xuanwei coal combustion has not previously been studied. In this study, PM1 and ultrafine particles emitted from Xuanwei coal combustion were sampled. Chemical elements in the ambient particles were analyzed by inductively coupled plasma mass spectrometry (ICP-MS), and mineralogical characterization of these ambient particles was investigated using scanning electronic microscopy (SEM/EDX) and transmission electronic microscopy, coupled with energy-dispersive spectroscopy (TEM/EDX). Our results showed that the size distribution of mineral particles from the coal combustion emissions ranged from 20 to 200 nm. Si-containing particles and Fe-containing particles accounted for 50.7% of the 150 individual particles measured, suggesting that these two types of particles were major minerals in the ambient particles generally. The nano-mineral particles were identified as quartz (SiO2) and gypsum (CaSO4) based on their crystal parameters and chemical elements. Additionally, there also existed unidentified nano-minerals. Armed with these data, toxicity assessments of the nano-minerals will be carried out in a future study.

  2. Assimilation of formaldehyde and other C1-compounds by Gliocladium deliquescens and Paecilomyces varioti

    International Nuclear Information System (INIS)

    Two fungi were isolated from soil which grew on 0.1--0.2% formaldehyde as the sole carbon source, and identified as Gliocladium deliquescens and Paecilomyces varioti. Both the strains could grow on 5% methanol and 5% Na-formate, while the former could grow even on 7% methanol. Metabolic pathways were traced through two dimensional paper chromatography and autoradiographic techniques using 14C-formaldehyde, 14C-methanol or 14C-CO2 as substrates. The intracellular metabolites were persued and their quantitative variation with time was measured. Along with the fact that serine and malate appeared in the earlier time, then appeared organic acids and amino acids belonging to TCA cycle, and the fact that hydroxy-pyruvate reductase and phosphoenolpyruvate carboxylase activities were much stronger in methanol culture than in ethanol culture, it was concluded that the two fungi followed the serine pathway in assimilating C1-compounds. Oxidation enzymes of methanol and formaldehyde were also studied, and an oxidizing system was found besides usual NAD linked methanol or formaldehyde dehydrogenases. (auth.)

  3. Precision Measurement of the Mass of the h_c(1P1) State of Charmonium

    CERN Document Server

    Dobbs, S; Seth, K K; Tomaradze, A G; Libby, J; Powell, A; Wilkinson, G; Ecklund, K M; Love, W; Savinov, V; López, A; Méndez, H; Ramírez, J; Ge, J Y; Miller, D H; Shipsey, I P J; Xin, B; Adams, G S; Anderson, M; Cummings, J P; Danko, I; Hu, D; Moziak, B; Napolitano, J; He, Q; Insler, J; Muramatsu, H; Park, C S; Thorndike, E H; Yang, F; Artuso, M; Blusk, S; Khalil, S; Li, J; Mountain, R; Nisar, S; Randrianarivony, K; Sultana, N; Skwarnicki, T; Stone, S; Wang, J C; Zhang, L M; Bonvicini, G; Cinabro, D; Dubrovin, M; Lincoln, A; Naik, P; Rademacker, J; Asner, D M; Edwards, K W; Reed, J; Briere, R A; Ferguson, T; Tatishvili, G; Vogel, H; Watkins, M E; Rosner, J L; Alexander, J P; Cassel, D G; Duboscq, J E; Ehrlich, R; Fields, L; Galik, R S; Gibbons, L; Gray, R; Gray, S W; Hartill, D L; Heltsley, B K; Hertz, D; Hunt, J M; Kandaswamy, J; Kreinick, D L; Kuznetsov, V E; Ledoux, J; Mahlke-Krüger, H; Mohapatra, D; Onyisi, P U E; Patterson, J R; Peterson, D; Riley, D; Ryd, A; Sadoff, A J; Shi, X; Stroiney, S; Sun, W M; Wilksen, T; Athar, S B; Patel, R; Yelton, J; Rubin, P; Eisenstein, B I; Karliner, I; Mehrabyan, S; Lowrey, N; Selen, M; White, E J; Wiss, J; Mitchell, R E; Shepherd, M R; Besson, D; Pedlar, T K; Cronin-Hennessy, D; Gao, K Y; Hietala, J; Kubota, Y; Klein, T; Lang, B W; Poling, R; Scott, A W; Zweber, P

    2008-01-01

    A precision measurement of the mass of the h_c(1P1) state of charmonium has been made using a sample of 24.5 million psi(2S) events produced in e+e- annihilation at CESR. The reaction used was psi(2S) -> pi0 h_c, pi0 -> gamma gamma, h_c -> gamma eta_c, and the reaction products were detected in the CLEO-c detector. Data have been analyzed both for the inclusive reaction and for the exclusive reactions in which eta_c decays are reconstructed in fifteen hadronic decay channels. Consistent results are obtained in the two analyses. The averaged results of the present measurements are M(h_c)=3525.28+-0.19 (stat)+-0.12(syst) MeV, and B(psi(2S) -> pi0 h_c)xB(h_c -> gamma eta_c)= (4.19+-0.32+-0.45)x10^-4. Using the 3PJ centroid mass, Delta M_hf(1P)= - M(h_c) = +0.02+-0.19+-0.13 MeV.

  4. Toward the accurate analysis of C1-C4 polycyclic aromatic sulfur heterocycles.

    Science.gov (United States)

    Zeigler, Christian; Wilton, Nicholas; Robbat, Albert

    2012-03-01

    Polycyclic aromatic sulfur heterocycles (PASH) are sulfur analogues of polycyclic aromatic hydrocarbons (PAH). Alkylated PAH attract much attention as carcinogens, mutagens, and as diagnostics for environmental forensics. PASH, in contrast, are mostly ignored in the same studies due to the conspicuous absence of gas chromatography/mass spectrometry (GC/MS) retention times and fragmentation patterns. To obtain these data, eight coal tar and crude oils were analyzed by automated sequential GC-GC. Sample components separated based on their interactions with two different stationary phases. Newly developed algorithms deconvolved combinatorially selected ions to identify and quantify PASH in these samples. Simultaneous detection by MS and pulsed flame photometric detectors (PFPD) provided additional selectivity to differentiate PASH from PAH when coelution occurred. A comprehensive library of spectra and retention indices is reported for the C(1)-C(4) two-, three-, and four-ring PASH. Results demonstrate the importance of using multiple fragmentation patterns per homologue (MFPPH) compared to selected ion monitoring (SIM) or extraction (SIE) to identify isomers. Since SIM/SIE analyses dramatically overestimate homologue concentrations, MFPPH should be used to correctly quantify PASH for bioavailability, weathering, and liability studies. PMID:22339202

  5. Sterol-modulated glycolipid sorting occurs in niemann-pick C1 late endosomes.

    Science.gov (United States)

    Zhang, M; Dwyer, N K; Neufeld, E B; Love, D C; Cooney, A; Comly, M; Patel, S; Watari, H; Strauss, J F; Pentchev, P G; Hanover, J A; Blanchette-Mackie, E J

    2001-02-01

    The Niemann-Pick C1 (NPC1) protein and endocytosed low density lipoprotein (LDL)-derived cholesterol were shown to enrich separate subsets of vesicles containing lysosomal associated membrane protein 2. Localization of Rab7 in the NPC1-containing vesicles and enrichment of lysosomal hydrolases in the cholesterol-containing vesicles confirmed that these organelles were late endosomes and lysosomes, respectively. Lysobisphosphatidic acid, a lipid marker of the late endosomal pathway, was found in the cholesterol-enriched lysosomes. Recruitment of NPC1 to Rab7 compartments was stimulated by cellular uptake of cholesterol. The NPC1 compartment was shown to be enriched in glycolipids, and internalization of GalNAcbeta1-4[NeuAcalpha2-3]Galbeta1-4Glcbeta1-1'-ceramide (G(M2)) into endocytic vesicles depends on the presence of NPC1 protein. The glycolipid profiles of the NPC1 compartment could be modulated by LDL uptake and accumulation of lysosomal cholesterol. Expression in cells of biologically active NPC1 protein fused to green fluorescent protein revealed rapidly moving and flexible tubular extensions emanating from the NPC1-containing vesicles. We conclude that the NPC1 compartment is a dynamic, sterol-modulated sorting organelle involved in the trafficking of plasma membrane-derived glycolipids as well as plasma membrane and endocytosed LDL cholesterol. PMID:11032830

  6. Modelling Al-4wt.%Cu as-cast structure using equiaxed morphological parameters deduced from in-situ synchrotron X-ray radiography

    Science.gov (United States)

    Ahmadein, M.; Wu, M.; Reinhart, G.; Nguyen-Thi, H.; Ludwig, A.

    2016-03-01

    The as-cast structure of laboratory scale Al-4wt.%Cu was numerically calculated using assumed morphological parameters. Two parameters are identified: The shape factor which correlates the growth velocity of dendrite envelope to that of the tip; and the sphericity of the equiaxed envelope or the circularity of the columnar trunk envelope which is required to calculate the averaged species diffusion flux across the envelope. In the present work, the real-time radiographs of equiaxed solidification experiment carried out on Al-4wt.%Cu at the European Synchrotron Radiation Facility are used to track the development of crystal envelope with time. The growth rate of the equivalent circular envelope was correlated to dendrite tip growth velocity to deduce the shape factor. The sphericity of dendrite envelope is estimated over the time. The average of the deduced morphological parameters is applied to the model to predict the as-cast structure. The results were compared to those obtained by using morphological parameters from literature. The predicted phase quantities, columnar-to- equiaxed transition, and macrosegregation exhibited significant dependence on those parameters. The predicted macrosegregation using the experimentally deduced parameters fits better to the measurements.

  7. Successful C1 inhibitor short-term prophylaxis during redo mitral valve replacement in a patient with hereditary angioedema

    Directory of Open Access Journals (Sweden)

    Coleman Suzanne

    2010-10-01

    Full Text Available Abstract Hereditary angioedema is characterized by sudden episodes of nonpitting edema that cause discomfort and pain. Typically the extremities, genitalia, trunk, gastrointestinal tract, face, and larynx are affected by attacks of swelling. Laryngeal swelling carries significant risk for asphyxiation. The disease results from mutations in the C1 esterase inhibitor gene that cause C1 esterase inhibitor deficiency. Attacks of hereditary angioedema result from contact, complement, and fibrinolytic plasma cascade activation, where C1 esterase inhibitor irreversibly binds substrates. Patients with hereditary angioedema cannot replenish C1 esterase inhibitor levels on pace with its binding. When C1 esterase inhibitor is depleted in these patients, vasoactive plasma cascade products cause swelling attacks. Trauma is a known trigger for hereditary angioedema attacks, and patients have been denied surgical procedures because of this risk. However, uncomplicated surgeries have been reported. Appropriate prophylaxis can reduce peri-operative morbidity in these patients, despite proteolytic cascade and complement activation during surgical trauma. We report a case of successful short-term prophylaxis with C1 esterase inhibitor in a 51-year-old man with hereditary angioedema who underwent redo mitral valve reconstructive surgery.

  8. Os odontoideum with "free-floating" atlantal arch causing C1-2 anterolisthesis and retrolisthesis with cervicomedullary compression

    Directory of Open Access Journals (Sweden)

    Behari Sanjay

    2010-01-01

    Full Text Available Background: Os odontoideum (OO with C1-2 anterolisthesis and retrolisthesis may cause cervicomedullary injury both from anterior and posterior aspects. We analyzed fourteen such patients for biomechanical issues, radiological features and management of OO with free-floating atlantal arch and review pertinent literature. Materials and Methods: Fourteen patients having nonsyndromic, reducible atlantoaxial dislocation (AAD with orthotopic OO were analyzed. During neck flexion, their C1 anterior arch-os complex displaced anteriorly relative to remnant odontoid-C2 body. The posteriorly directed hypoplastic remnant odontoid sliding below the atlas and forward translation of the C1 posterior arch caused concomitant cervicomedullary compression. During neck extension, there was retrolisthesis of the "free-floating" C1 arch-os complex into spinal canal. Spinal stenosis and lateral C1-2 facet dislocation; Klippel-Feil anomaly; and posterior circulation infarcts were also present in one patient each, respectively. Posterior C1-2 (n=10 or occipitocervical fusion (n=3 was performed in neutral position to stabilize atlantoaxial movements. Results: Follow-up (mean, 3.9 years assessment revealed improvement in spasticity and weakness in 13 patients. One patient had neurological deterioration following C1-2 posterior sublaminar fusion, requiring its conversion to occipitocervical contoured rod fusion. One patient with posterior circulation stroke died prior to any operative intervention. Follow-up lateral view radiographs showed a bony union or a stable construct in these 13 patients. Conclusions: OO with free-floating atlantal arch may precipitate cord injury both during neck flexion and extension. This condition may be overlooked unless lateral radiographs of craniovertebral junction are undertaken in neck extension, along with the usual ones in neutral and flexed positions. Etiological factors include C1 ring-OO unrestrained movements above the hypoplastic

  9. Cross-sectional study of C1–S5 vertebral bodies in human fetuses

    Science.gov (United States)

    Baumgart, Mariusz; Szpinda, Anna; Woźniak, Alina; Mila-Kierzenkowska, Celestyna

    2014-01-01

    Introduction Knowledge on the normative spinal growth is relevant in the prenatal detection of its abnormalities. The present study determines the height, transverse and sagittal diameters, cross sectional area, and volume of individual C1–S5 vertebral bodies. Material and methods Using the methods of computed tomography (CT), digital image analysis, and statistics, the size of C1–S5 vertebral bodies in 55 spontaneously aborted human fetuses aged 17–30 weeks was examined. Results All the 5 examined parameters changed significantly with gestational age (p < 0.01). The mean height of vertebral bodies revealed an increase from the atlas (2.39 ±0.54 mm) to L2 (4.62 ±0.97 mm), stabilized through L3–L4 (4.58 ±0.92 mm, 4.61 ±0.84 mm), and then was decreasing to S5 (0.43 ±1.06 mm). The mean transverse diameter of vertebral bodies was increasing from the atlas (1.20 ±1.96 mm) to L1 (6.24 ±1.46 mm), so as to stabilize through L2–L3 (6.12 ±1.65, 6.12 ±1.61 mm), and finally was decreasing to S5 (0.26 ±0.96 mm). There was an increase in sagittal diameter of vertebral bodies from the atlas (0.82 ±1.34 mm) to T7 (4.76 ±0.85 mm), its stabilization for T8–L4 (4.73 ±0.86 mm, 4.71 ±1.02 mm), and then a decrease in values to S5 (0.21 ±0.75 mm) was observed. The values for cross-sectional area of vertebral bodies were increasing from the atlas (2.95 ±5.25 mm2) to L3 (24.92 ±11.07 mm2), and then started decreasing to S5 (0.48 ±2.09 mm2). The volumetric growth of vertebral bodies was increasing from the atlas (8.60 ±16.40 mm3) to L3 (122.16 ±74.73 mm3), and then was decreasing to S5 (1.60 ±7.00 mm3). Conclusions There is a sharp increase in size of fetal vertebral bodies between the atlas and the axis, and a sharp decrease in size within the sacral spine. In human fetuses the vertebral body growth is characterized by maximum values in sagittal diameter for T7, in transverse diameter for L1, in height for L2, and in both cross-sectional area and volume for

  10. Temporal variability, sources, and sinks of C1-C5 alkyl nitrates in coastal New England

    Directory of Open Access Journals (Sweden)

    B. C. Sive

    2010-02-01

    Full Text Available Seven C1-C5 alkyl nitrates were measured both on the mainland and off the coast of New Hampshire using gas chromatographic techniques. Five separate data sets are presented to characterize the seasonal and diurnal trends and the major sources and loss processes of these compounds. Based on in situ measurements conducted at the University of New Hampshire (UNH Atmospheric Observing Station at Thompson Farm (TF located in southeast NH during winter (January–February 2002, summer (June–August 2002, summer (July–August 2004, and on daily canister samples collected at midday from January 2004–February 2008, the median total alkyl nitrate mixing ratio (ΣRONO2 was 23–25 pptv in winter and 14–16 pptv in summer. During summers 2002 and 2004, MeONO2 decreased overnight and reached minimum hourly average mixing ratios in the early morning. Comparison with wind speed and trace gas trends suggested that dry deposition contributed to the early morning MeONO2 minimum which is a previously unaccounted for removal mechanism. The mean dry deposition rate and velocity of MeONO2 was estimated to be −0.5 nmol m−2 hr−1 and 0.13 cm s−1, respectively. Results from ambient air and surface seawater measurements made onboard the NOAA R/V Ronald H. Brown in the Gulf of Maine during the 2002 New England Air Quality Study and from ambient canister samples collected throughout the Great Bay estuary in August 2003 are also presented. Comparisons between the alkyl nitrate trends with anthropogenic and marine tracers suggest that a marine source of alkyl nitrates is not significant in coastal New England. Given the apparent prominence of a secondary source, comparisons between observed and predicted alkyl nitrate/parent hydrocarbon ratios were made which demonstrated that background mixing ratios have a continuous and prevalent influence on the alkyl nitrate distribution.

  11. OPTICAL SPECTRAL OBSERVATIONS OF A FLICKERING WHITE-LIGHT KERNEL IN A C1 SOLAR FLARE

    Energy Technology Data Exchange (ETDEWEB)

    Kowalski, Adam F. [Goddard Space Flight Center, Code 671, 8800 Greenbelt Road, Greenbelt, MD 20771 (United States); Cauzzi, Gianna [INAF-Osservatorio Astrofisico di Arcetri, Firenze, Italy and National Solar Observatory, Sunspot NM (United States); Fletcher, Lyndsay, E-mail: adam.f.kowalski@nasa.gov [SUPA School of Physics and Astronomy, University of Glasgow, Glasgow G12 8QQ (United Kingdom)

    2015-01-10

    We analyze optical spectra of a two-ribbon, long-duration C1.1 flare that occurred on 2011 August 18 within AR 11271 (SOL2011-08-18T15:15). The impulsive phase of the flare was observed with a comprehensive set of space-borne and ground-based instruments, which provide a range of unique diagnostics of the lower flaring atmosphere. Here we report the detection of enhanced continuum emission, observed in low-resolution spectra from 3600 Å to 4550 Å acquired with the Horizontal Spectrograph at the Dunn Solar Telescope. A small, ≤0.''5 (10{sup 15} cm{sup 2}) penumbral/umbral kernel brightens repeatedly in the optical continuum and chromospheric emission lines, similar to the temporal characteristics of the hard X-ray variation as detected by the Gamma-ray Burst Monitor on the Fermi spacecraft. Radiative-hydrodynamic flare models that employ a nonthermal electron beam energy flux high enough to produce the optical contrast in our flare spectra would predict a large Balmer jump in emission, indicative of hydrogen recombination radiation from the upper flare chromosphere. However, we find no evidence of such a Balmer jump in the bluemost spectral region of the continuum excess. Just redward of the expected Balmer jump, we find evidence of a ''blue continuum bump'' in the excess emission which may be indicative of the merging of the higher order Balmer lines. The large number of observational constraints provides a springboard for modeling the blue/optical emission for this particular flare with radiative-hydrodynamic codes, which are necessary to understand the opacity effects for the continuum and emission line radiation at these wavelengths.

  12. Fine analysis of spontaneous MAGE-C1/CT7-specific immunity in melanoma patients.

    Science.gov (United States)

    Nuber, Natko; Curioni-Fontecedro, Alessandra; Matter, Claudia; Soldini, Davide; Tiercy, Jean Marie; von Boehmer, Lotta; Moch, Holger; Dummer, Reinhard; Knuth, Alexander; van den Broek, Maries

    2010-08-24

    Cancer/testis (CT) antigens represent prime candidates for immunotherapy in cancer patients, because their expression is restricted to cancer cells and germ cells of the testis. MAGE-C1/CT7 is a CT antigen that is highly expressed in several types of cancers. Spontaneous occurrence of CT7-specific antibodies was previously detected by SEREX screen in a melanoma patient. However, naturally occurring CT7-specific T-cell responses have thus far not been detected. Peripheral blood mononuclear cells (PBMCs) from 26 metastatic melanoma patients expressing CT7 in their tumor lesions (CT7(+)) were analyzed for CT7-specific T-cell responses using overlapping peptides. CT7-specific CD4(+) T-cell responses were detected in three patients (11.5%). These CT7-specific CD4(+) T-cell responses were detectable in melanoma patients' PBMCs exclusively from preexisting CD45RA(-) memory CD4(+) T-cell pool. Additional CT7-specific memory CD4(+) T-cell responses were detected in CT7(+) melanoma patients after depletion of CD4(+)CD25high Treg cells showing that Treg cells impact on CT7-specific CD4(+) T cells in melanoma patients. CT7-specific CD4(+) T-cell clones were generated and used to define minimal epitopes, restriction elements, and confirm the recognition of naturally processed antigen. Surprisingly, these clones were able to secrete perforin and exert cytotoxicity. This study shows that CT7 can induce specific cellular immunity in melanoma patients. Based on these findings, CT7 will be further explored as a potential vaccine for melanoma immunotherapy. PMID:20696919

  13. OPTICAL SPECTRAL OBSERVATIONS OF A FLICKERING WHITE-LIGHT KERNEL IN A C1 SOLAR FLARE

    International Nuclear Information System (INIS)

    We analyze optical spectra of a two-ribbon, long-duration C1.1 flare that occurred on 2011 August 18 within AR 11271 (SOL2011-08-18T15:15). The impulsive phase of the flare was observed with a comprehensive set of space-borne and ground-based instruments, which provide a range of unique diagnostics of the lower flaring atmosphere. Here we report the detection of enhanced continuum emission, observed in low-resolution spectra from 3600 Å to 4550 Å acquired with the Horizontal Spectrograph at the Dunn Solar Telescope. A small, ≤0.''5 (1015 cm2) penumbral/umbral kernel brightens repeatedly in the optical continuum and chromospheric emission lines, similar to the temporal characteristics of the hard X-ray variation as detected by the Gamma-ray Burst Monitor on the Fermi spacecraft. Radiative-hydrodynamic flare models that employ a nonthermal electron beam energy flux high enough to produce the optical contrast in our flare spectra would predict a large Balmer jump in emission, indicative of hydrogen recombination radiation from the upper flare chromosphere. However, we find no evidence of such a Balmer jump in the bluemost spectral region of the continuum excess. Just redward of the expected Balmer jump, we find evidence of a ''blue continuum bump'' in the excess emission which may be indicative of the merging of the higher order Balmer lines. The large number of observational constraints provides a springboard for modeling the blue/optical emission for this particular flare with radiative-hydrodynamic codes, which are necessary to understand the opacity effects for the continuum and emission line radiation at these wavelengths

  14. Cloud effect on the radiation budget of the calculated with the ISCCP C1 data

    International Nuclear Information System (INIS)

    This study examines the cloud effect on the radiation budget at the top of the atmosphere by use of the ISCCP daylight cloud data (C1) in combination with a Two-Stream-Model. Two tests are performed: the modelled narrowband filtered radiances are verified against the ISCCP satellite observation data (internal test) and the modelled broadband fluxes are compared against ERBE data (external tests). After both tests are succesfully concluded, the outgoing longwave radiation (OLR) for each of the 35 ISCCP cloud classes are determined. For better clarity we summarized the 35 cloud classes into 9 ones (3 top heights, 3 optical depths). Global monthly and annual means of the albedo and greenhouse effect of these 9 cloud types are given for one month of each season (April, July, October 1985, January 1986). For the global annual mean cloud radiative cooling of the earth in the shortwave spectral range dominates over cloud radiative warming in the longwave spectral range by a factor of 2. Seasonal variations of the net effect are mainly due to the changes in the shortwave cloud forcing component (-43.3 to -52.9 Wm-2 (shortwave), 22.5 to 25.1 Wm-2 (longwave)). The mean cloud sensitivity related to cloud amount changes from -29.4 to -47.7 Wm-2. This is mainly due to the difference between the mean surface albedo of northern and southern hemisphere. A comparison with the results of other studies are shown. The effects of the 9 different cloud types are analysed in detail. Cooling, warming, and radiatively neutral cloud types could be distinguished. (orig.)

  15. Expression of CYP1C1 and CYP1A in Fundulus heteroclitus during PAH-induced carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Wang Lu [Pharmacology and Environmental Toxicology, University of Mississippi, University, MS (United States); Camus, Alvin C. [Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA (United States); Dong, Wu; Thornton, Cammi [Pharmacology and Environmental Toxicology, University of Mississippi, University, MS (United States); Willett, Kristine L., E-mail: kwillett@olemiss.edu [Pharmacology and Environmental Toxicology, University of Mississippi, University, MS (United States)

    2010-09-15

    CYP1C1 is a relatively newly identified member of the cytochrome P450 family 1 in teleost fish. However, CYP1C1's expression and physiological roles relative to the more recognized CYP1A in polycyclic aromatic hydrocarbons (PAHs) induced toxicities are unclear. Fundulus heteroclitus fry were exposed at 6-8 days post-hatch (dph) and again at 13-15 dph for 6 h to dimethyl sulfoxide (DMSO) control, 5 mg/L benzo[a]pyrene (BaP), or 5 mg/L dimethylbenzanthracene (DMBA). Fry were euthanized at 0, 6, 18, 24 and 30 h after the second exposure. In these groups, both CYP1A and CYP1C1 protein expression were induced within 6 h after the second exposure. Immunohistochemistry (IHC) results from fry revealed strongest CYP1C1 expression in renal tubular and intestinal epithelial cells. Additional fish were examined for liver lesions 8 months after initial exposure. Gross lesions were observed in 20% of the BaP and 35% of the DMBA-treated fish livers. Histopathologic findings included foci of cellular alteration and neoplasms, including hepatocellular adenoma, hepatocellular carcinoma and cholangioma. Strong CYP1A immunostaining was detected diffusely in altered cell foci and on the invading margin of hepatocelluar carcinomas. Lower CYP1A expression was seen in central regions of the neoplasms. In contrast, CYP1C1 was only detectable and highly expressed in proliferated bile duct epithelial cells. Our CYP1C1 results suggest the potential for tissue specific CYP1C1-mediated PAH metabolism but not a more chronic role in progression to liver hepatocellular carcinoma.

  16. Haploinsufficiency for NR3C1, the gene encoding the glucocorticoid receptor, in blastic plasmacytoid dendritic cell neoplasms.

    Science.gov (United States)

    Emadali, Anouk; Hoghoughi, Neda; Duley, Samuel; Hajmirza, Azadeh; Verhoeyen, Els; Cosset, Francois-Loic; Bertrand, Philippe; Roumier, Christophe; Roggy, Anne; Suchaud-Martin, Céline; Chauvet, Martine; Bertrand, Sarah; Hamaidia, Sieme; Rousseaux, Sophie; Josserand, Véronique; Charles, Julie; Templier, Isabelle; Maeda, Takahiro; Bruder-Costa, Juliana; Chaperot, Laurence; Plumas, Joel; Jacob, Marie-Christine; Bonnefoix, Thierry; Park, Sophie; Gressin, Remy; Tensen, Cornelis P; Mecucci, Cristina; Macintyre, Elizabeth; Leroux, Dominique; Brambilla, Elisabeth; Nguyen-Khac, Florence; Luquet, Isabelle; Penther, Dominique; Bastard, Christian; Jardin, Fabrice; Lefebvre, Christine; Garnache, Francine; Callanan, Mary B

    2016-06-16

    Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and highly aggressive leukemia for which knowledge on disease mechanisms and effective therapies are currently lacking. Only a handful of recurring genetic mutations have been identified and none is specific to BPDCN. In this study, through molecular cloning in an index case that presented a balanced t(3;5)(q21;q31) and molecular cytogenetic analyses in a further 46 cases, we identify monoallelic deletion of NR3C1 (5q31), encoding the glucocorticoid receptor (GCR), in 13 of 47 (28%) BPDCN patients. Targeted deep sequencing in 36 BPDCN cases, including 10 with NR3C1 deletion, did not reveal NR3C1 point mutations or indels. Haploinsufficiency for NR3C1 defined a subset of BPDCN with lowered GCR expression and extremely poor overall survival (P = .0006). Consistent with a role for GCR in tumor suppression, functional analyses coupled with gene expression profiling identified corticoresistance and loss-of-EZH2 function as major downstream consequences of NR3C1 deletion in BPDCN. Subsequently, more detailed analyses of the t(3;5)(q21;q31) revealed fusion of NR3C1 to a long noncoding RNA (lncRNA) gene (lincRNA-3q) that encodes a novel, nuclear, noncoding RNA involved in the regulation of leukemia stem cell programs and G1/S transition, via E2F. Overexpression of lincRNA-3q was a consistent feature of malignant cells and could be abrogated by bromodomain and extraterminal domain (BET) protein inhibition. Taken together, this work points to NR3C1 as a haploinsufficient tumor suppressor in a subset of BPDCN and identifies BET inhibition, acting at least partially via lncRNA blockade, as a novel treatment option in BPDCN. PMID:27060168

  17. Hereditary angioedema in a Jordanian family with a novel missense mutation in the C1-inhibitor N-terminal domain.

    Science.gov (United States)

    Jaradat, Saied A; Caccia, Sonia; Rawashdeh, Rifaat; Melhem, Motasem; Al-Hawamdeh, Ali; Carzaniga, Thomas; Haddad, Hazem

    2016-03-01

    Hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE) is an autosomal dominant disease caused by mutations in the SERPING1 gene. A Jordanian family, including 14 individuals with C1-INH-HAE clinical symptoms, was studied. In the propositus and his parents, SERPING1 had four mutations leading to amino acid substitutions. Two are known polymorphic variants (c.167T>C; p.Val34Ala and c.1438G>A; p.Val458Met), the others are newly described. One (c.203C>T; p.Thr46Ile) is located in the N-terminal domain of the C1-inhibitor protein and segregates with angioedema symptoms in the family. The other (c.800C>T; p.Ala245Val) belongs to the serpin domain, and derives from the unaffected father. DNA from additional 24 family members were screened for c.203C>T mutation in the target gene. All individuals heterozygous for the c.203C>T mutation had antigenic and functional plasma levels of C1-inhibitor below 50% of normal, confirming the diagnosis of type I C1-INH-HAE. Angioedema symptoms were present in 14 of 16 subjects carrier for the c.203T allele. Among these subjects, those carrying the c.800T variation had more severe and frequent symptoms than subjects without this mutation. This family-based study provides the first evidence that multiple amino acid substitutions in SERPING1 could influence C1-INH-HAE phenotype. PMID:26895475

  18. Complement factors C1q, C3 and C5 in brain and serum of mice with cerebral malaria

    Directory of Open Access Journals (Sweden)

    Helbok Raimund

    2008-10-01

    Full Text Available Abstract Background The patho-mechanisms leading to brain damage due to cerebral malaria (CM are yet not fully understood. Immune-mediated and ischaemic mechanisms have been implicated. The role of complement factors C1q, C3 and C5 for the pathogenesis of CM were investigated in this study. Methods C57BL/6J mice were infected with Plasmodium berghei ANKA blood stages. The clinical severity of the disease was assessed by a battery of 40 standardized tests for evaluating neurological functions in mice. Brain homogenates and sera of mice with CM, infected animals without CM and non-infected control animals were analyzed for C1q, C3 and C5 up-regulation by Western blotting. Results Densitometric analysis of Western blots of brain homogenates yielded statistically significant differences in the levels of C1q and C5 in the analyzed groups. Correlation analysis showed a statistically significant association of C1q and C5 levels with the clinical severity of the disease. More severely affected animals showed higher levels of C1q and C5. No differences in complement levels were observed between frontal and caudal parts of the brain. Densitometric analysis of Western blot of sera yielded statistically lower levels of C1q in infected animals without CM compared to animals of the control group. Conclusion The current study provides direct evidence for up-regulation of complement factors C1q and C5 in the brains of animals with CM. Local complement up-regulation is a possible mechanism for brain damage in experimental cerebral malaria.

  19. Expression of CYP1C1 and CYP1A in Fundulus heteroclitus during PAH-induced carcinogenesis

    International Nuclear Information System (INIS)

    CYP1C1 is a relatively newly identified member of the cytochrome P450 family 1 in teleost fish. However, CYP1C1's expression and physiological roles relative to the more recognized CYP1A in polycyclic aromatic hydrocarbons (PAHs) induced toxicities are unclear. Fundulus heteroclitus fry were exposed at 6-8 days post-hatch (dph) and again at 13-15 dph for 6 h to dimethyl sulfoxide (DMSO) control, 5 mg/L benzo[a]pyrene (BaP), or 5 mg/L dimethylbenzanthracene (DMBA). Fry were euthanized at 0, 6, 18, 24 and 30 h after the second exposure. In these groups, both CYP1A and CYP1C1 protein expression were induced within 6 h after the second exposure. Immunohistochemistry (IHC) results from fry revealed strongest CYP1C1 expression in renal tubular and intestinal epithelial cells. Additional fish were examined for liver lesions 8 months after initial exposure. Gross lesions were observed in 20% of the BaP and 35% of the DMBA-treated fish livers. Histopathologic findings included foci of cellular alteration and neoplasms, including hepatocellular adenoma, hepatocellular carcinoma and cholangioma. Strong CYP1A immunostaining was detected diffusely in altered cell foci and on the invading margin of hepatocelluar carcinomas. Lower CYP1A expression was seen in central regions of the neoplasms. In contrast, CYP1C1 was only detectable and highly expressed in proliferated bile duct epithelial cells. Our CYP1C1 results suggest the potential for tissue specific CYP1C1-mediated PAH metabolism but not a more chronic role in progression to liver hepatocellular carcinoma.

  20. Hereditary and acquired angioedema: problems and progress: proceedings of the third C1 esterase inhibitor deficiency workshop and beyond.

    Science.gov (United States)

    Agostoni, Angelo; Aygören-Pürsün, Emel; Binkley, Karen E; Blanch, Alvaro; Bork, Konrad; Bouillet, Laurence; Bucher, Christoph; Castaldo, Anthony J; Cicardi, Marco; Davis, Alvin E; De Carolis, Caterina; Drouet, Christian; Duponchel, Christiane; Farkas, Henriette; Fáy, Kálmán; Fekete, Béla; Fischer, Bettina; Fontana, Luigi; Füst, George; Giacomelli, Roberto; Gröner, Albrecht; Hack, C Erik; Harmat, George; Jakenfelds, John; Juers, Mathias; Kalmár, Lajos; Kaposi, Pál N; Karádi, István; Kitzinger, Arianna; Kollár, Tímea; Kreuz, Wolfhart; Lakatos, Peter; Longhurst, Hilary J; Lopez-Trascasa, Margarita; Martinez-Saguer, Inmaculada; Monnier, Nicole; Nagy, István; Németh, Eva; Nielsen, Erik Waage; Nuijens, Jan H; O'grady, Caroline; Pappalardo, Emanuela; Penna, Vincenzo; Perricone, Carlo; Perricone, Roberto; Rauch, Ursula; Roche, Olga; Rusicke, Eva; Späth, Peter J; Szendei, George; Takács, Edit; Tordai, Attila; Truedsson, Lennart; Varga, Lilian; Visy, Beáta; Williams, Kayla; Zanichelli, Andrea; Zingale, Lorenza

    2004-09-01

    Hereditary angioedema (HAE), a rare but life-threatening condition, manifests as acute attacks of facial, laryngeal, genital, or peripheral swelling or abdominal pain secondary to intra-abdominal edema. Resulting from mutations affecting C1 esterase inhibitor (C1-INH), inhibitor of the first complement system component, attacks are not histamine-mediated and do not respond to antihistamines or corticosteroids. Low awareness and resemblance to other disorders often delay diagnosis; despite availability of C1-INH replacement in some countries, no approved, safe acute attack therapy exists in the United States. The biennial C1 Esterase Inhibitor Deficiency Workshops resulted from a European initiative for better knowledge and treatment of HAE and related diseases. This supplement contains work presented at the third workshop and expanded content toward a definitive picture of angioedema in the absence of allergy. Most notably, it includes cumulative genetic investigations; multinational laboratory diagnosis recommendations; current pathogenesis hypotheses; suggested prophylaxis and acute attack treatment, including home treatment; future treatment options; and analysis of patient subpopulations, including pediatric patients and patients whose angioedema worsened during pregnancy or hormone administration. Causes and management of acquired angioedema and a new type of angioedema with normal C1-INH are also discussed. Collaborative patient and physician efforts, crucial in rare diseases, are emphasized. This supplement seeks to raise awareness and aid diagnosis of HAE, optimize treatment for all patients, and provide a platform for further research in this rare, partially understood disorder. PMID:15356535

  1. Study of the decay $B^0 \\to \\chi_{c1} K^+ \\pi^-$ and search of exotic resonances at LHCb

    CERN Document Server

    Sbordone, Francesco; Alves Junior, Antonio Augusto

    In 2008 the Belle Collaboration reported the observation of two charged resonance-like structures in the ${\\chi_c}_1 \\pi^-$ mass spectrum produced in the decay $B^0 \\to {\\chi_c}_1 K^+ \\pi^-$. These were labelled as $Z_1(4050)^-$ and $Z_2(4250)^-$. Alternatively, a single wider resonance hypothesis was also pursued by Belle, and labelled as $Z(4150)^-$. The fact that these are charged states would be a clear sample, if they really exist, of four quark bound systems; for this reason this observation has given rise to a great deal of interest. In 2012 the BABAR Collaboration has searched for these resonances in the channels $B^{0,+} \\to {\\chi_c}_1 K^{+,0} \\pi^-$ and did not find any evidence of them. In this thesis a search for these claimed exotic charmonium-like states $Z_1(4050)^-$ and $Z_2(4250)^-$ is presented, in the decay $B^0 \\to {\\chi_c}_1 K^+ \\pi^-$, where ${\\chi_c}_1 \\to J/\\psi \\gamma$ and $J/\\psi \\to \\mu^+ \\mu^-$. Charged conjugate are implied throughout the whole thesis. The analysis is performed us...

  2. Comparing the effects of symbiotic algae (Symbiodinium clades C1 and D on early growth stages of Acropora tenuis.

    Directory of Open Access Journals (Sweden)

    Ikuko Yuyama

    Full Text Available Reef-building corals switch endosymbiotic algae of the genus Symbiodinium during their early growth stages and during bleaching events. Clade C Symbiodinium algae are dominant in corals, although other clades - including A and D - have also been commonly detected in juvenile Acroporid corals. Previous studies have been reported that only molecular data of Symbiodinium clade were identified within field corals. In this study, we inoculated aposymbiotic juvenile polyps with cultures of clades C1 and D Symbiodinium algae, and investigated the different effect of these two clades of Symbiodinium on juvenile polyps. Our results showed that clade C1 algae did not grow, while clade D algae grew rapidly during the first 2 months after inoculation. Polyps associated with clade C1 algae exhibited bright green fluorescence across the body and tentacles after inoculation. The growth rate of polyp skeletons was lower in polyps associated with clade C1 algae than those associated with clade D algae. On the other hand, antioxidant activity (catalase of corals was not significantly different between corals with clade C1 and clade D algae. Our results suggested that clade D Symbiodinium algae easily form symbiotic relationships with corals and that these algae could contribute to coral growth in early symbiosis stages.

  3. Temporal variability, sources, and sinks of C1-C5 alkyl nitrates in Coastal New England

    Directory of Open Access Journals (Sweden)

    B. C. Sive

    2009-11-01

    Full Text Available Seven C1-C5 alkyl nitrates were measured both on the mainland and off the coast of New Hampshire using gas chromatographic techniques. Five separate data sets will be presented to characterize the seasonal and diurnal trends and the major sources and loss processes of these compounds. In situ measurements were conducted at the University of New Hampshire (UNH Atmospheric Observing Station at Thompson Farm (TF located in southeast NH during winter (January–February and summer (June–August 2002 and summer (July–August 2004. The median (±standard deviation total alkyl nitrate mixing ratio (ΣRONO2 was 25 (±7 in winter and 16 (±14 pptv in summer. Furthermore, daily canister samples collected at midday and later analyzed in the laboratory from January 2004–February 2008 gave median ΣRONO2 of 23 (±8 in winter and 14 (±10 pptv in summer. Alkyl nitrate mixing ratios increased throughout the morning and were highest in the afternoon reflecting mixing of remnant boundary layer air toward the surface and photochemical production during the day. During summers 2002 and 2004, MeONO2 decreased overnight and reached minimum hourly average mixing ratios in the early morning (05:00–07:00 LT. Comparison with wind speed and trace gas (i.e., hydrocarbons, ozone, carbon monoxide, total reactive nitrogen trends suggested that dry deposition contributed to the early morning MeONO2 minimum which is a previously unaccounted for removal mechanism. The mean dry deposition rate and velocity of MeONO2 was estimated to be −0.5 nmol m−2 hr−1 and 0.13 cm s−1, respectively. Results from ambient air and surface seawater measurements made onboard the NOAA R/V Ronald H. Brown in the Gulf of Maine during the 2002 New England Air Quality Study and from ambient canister samples collected throughout the Great Bay estuary in August 2003 are also presented. Comparisons between the alkyl nitrate trends with anthropogenic and marine source fingerprints and tracers

  4. Crystallization and preliminary X-ray analysis of CYP153C1 from Novosphingobium aromaticivorans DSM12444

    International Nuclear Information System (INIS)

    The expression, purification and preliminary crystallographic analysis of CYP153C1, an alkane-binding cytochrome P450 enzyme, are reported. Cytochrome P450 (CYP) enzymes constitute a large family of haemoproteins that catalyze the monooxygenation of a great variety of endogenous and exogenous organic compounds. In common with other members of the CYP153 family of alkane hydroxylases, CYP153C1 from the oligotrophic bacterium Novosphingobium aromaticivorans DSM 12444 can bind linear alkanes such as heptane, octane and nonane. Here, the production, purification and crystallization of CYP153C1 and the collection of high-resolution diffraction data to 1.77 Å resolution are reported. The crystals belonged to space group P212121, with unit-cell parameters a = 61.0, b = 96.3, c = 149.8 Å, α = β = γ = 90.0°. Preliminary X-ray diffraction data analysis revealed that the asymmetric unit is most likely to contain two protein molecules

  5. Cloning and heterologous expression of a novel insecticidal gene (tccC1) from Xenorhabdus nematophilus strain

    International Nuclear Information System (INIS)

    We have identified and cloned a novel toxin gene (tccC1/xptB1) from Xenorhabdus nematophilus strain isolated from Korea-specific entomophagous nematode Steinernema glaseri MK. The DNA sequence of cloned toxin gene (3048 bp) has an open reading frame encoding 1016 amino acids with a predicted molecular mass of 111058 Da. The toxin sequence shares 50-96% identical amino acid residues with the previously reported tccC1 cloned from X. nematophilus (AJ308438), Photorhabdus luminescens W14 (AF346499) P. luminescens TTO1 (BX571873), and Yersinia pestis CO92 (NC003143). The toxin gene was successfully expressed in Escherichia coli, and the recombinant toxin protein caused a rapid cessation in mortality of Galleria mellonella larvae (80% death of larvae within 2 days). Conclusively, the heterologous expression of the novel gene tccC1 cloned into E. coli plasmid vector produced recombinant toxin with high insecticidal activity

  6. Synthesis and deformation microstructure of Ti3SiAl0.2C1.8 solid solution

    International Nuclear Information System (INIS)

    Solid solution Ti3SiAl0.2C1.8 was synthesized by sintering powder compacts containing Ti, Si, Al, and C with a mole ratio of 3:1:0.2:1.8 at 1550 deg. C for 5 min in Ar. X-ray diffraction and scanning electron microscopy were used to characterize the samples. The results show that nearly single solid solution was obtained except for the presence of a small amount of TiC. The observation from the fracture surface shows that delamination, kink band formation and crack deflection are prevalent features in the deformed Ti3SiAl0.2C1.8 grains. The crystal parameters for Ti3SiAl0.2C1.8 were analyzed and the multiple energy dissipation mechanisms were discussed

  7. Prenylated chalcones and flavanones as inducers of quinone reductase in mouse Hepa 1c1c7 cells.

    Science.gov (United States)

    Miranda, C L; Aponso, G L; Stevens, J F; Deinzer, M L; Buhler, D R

    2000-02-28

    The objective of this study was to determine if prenylchalcones (open C-ring flavonoids) and prenylflavanones from hops and beer are inducers of quinone reductase (QR) in the mouse hepatoma Hepa 1c1c7 cell line. All the prenylchalcones and prenylflavanones tested were found to induce QR but not CYP1A1 in this cell line. In contrast, the synthetic chalcone, chalconaringenin, and the flavanone, naringenin, with no prenyl or geranyl groups, were ineffective in inducing QR. The hop chalcones, xanthohumol and dehydrocycloxanthohumol hydrate, also induced QR in the Ah-receptor-defective mutant cell line, Hepa 1c1c7 bp(r)c1. Thus, the prenylflavonoids represent a new class of monofunctional inducers of QR. PMID:10737704

  8. C1 Inhibitor in Acute Antibody-Mediated Rejection Nonresponsive to Conventional Therapy in Kidney Transplant Recipients: A Pilot Study.

    Science.gov (United States)

    Viglietti, D; Gosset, C; Loupy, A; Deville, L; Verine, J; Zeevi, A; Glotz, D; Lefaucheur, C

    2016-05-01

    Complement inhibitors have not been thoroughly evaluated in the treatment of acute antibody-mediated rejection (ABMR). We performed a prospective, single-arm pilot study to investigate the potential effects and safety of C1 inhibitor (C1-INH) Berinert added to high-dose intravenous immunoglobulin (IVIG) for the treatment of acute ABMR that is nonresponsive to conventional therapy. Kidney recipients with nonresponsive active ABMR and acute allograft dysfunction were enrolled between April 2013 and July 2014 and received C1-INH and IVIG for 6 months (six patients). The primary end point was the change in eGFR at 6 months after inclusion (M+6). Secondary end points included the changes in histology and DSA characteristics and adverse events as evaluated at M+6. All patients showed an improvement in eGFR between inclusion and M+6: from 38.7 ± 17.9 to 45.2 ± 21.3 mL/min/1.73 m(2) (p = 0.0277). There was no change in histological features, except a decrease in the C4d deposition rate from 5/6 to 1/6 (p = 0.0455). There was a change in DSA C1q status from 6/6 to 1/6 positive (p = 0.0253). One deep venous thrombosis was observed. In a secondary analysis, C1-INH patients were compared with a similar historical control group (21 patients). C1-INH added to IVIG is safe and may improve allograft function in kidney recipients with nonresponsive acute ABMR. PMID:26693703

  9. Metabolism and macromolecular covalent binding of [14C]-1-nitropyrene in isolated perfused and ventilated rat lungs

    International Nuclear Information System (INIS)

    The purpose of this study was to quantitate l-nitropyrene (1-NP) metabolism and macromolecular covalent binding in the isolated perfused rat lung. Rat lungs were perfused with 2, 5, or 24 microM [14C]-1-NP for 90 min. Tidal volume and dynamic lung compliance were monitored throughout the perfusion to document the ventilatory pattern and the decay of tissue elasticity. Perfusate was sampled periodically throughout the experiment and analyzed for 1-NP metabolites with high-performance liquid chromatography. In all experiments, both dynamic lung compliance and tidal volume declined in a nearly linear manner and were approximately 60% of the initial value at the end of 90 min of perfusion. At all concentrations of [14C]-1-NP tested, less than 5 to 6% of the total amount of [14C]-1-NP added was metabolized in lungs from control and phenobarbital (PB)-treated rats. Lungs from control and PB- and 3-methylcholanthrene (3-MC)-treated rats metabolized [14C]-1-NP to oxidized, reduced, and conjugated metabolites. The major metabolites were 3-, 6-, and 8-hydroxynitropyrene. Treatment of rats with PB resulted in a 60% increase in the total metabolism of [14C]-1-NP, whereas treatment of rats with 3-MC resulted in a 10-fold increase in the rate of metabolism of [14C]-1-NP when compared to controls. Conjugate hydrolysis studies indicated that the water-soluble metabolites from lungs of control and PB- and 3-MC-treated rats consisted of hydroxynitropyrene glucuronides and hydroxynitropyrene sulfate conjugates. Quantities of 14C covalently bound to lung macromolecules after 90 min of perfusion from lungs of control and PB-treated rats were 0.06 to 0.21 nmol equivalents/g lung. However, in lungs from 3-MC-treated rats, there was a 20-fold increase in quantities of 14C covalently bound when compared to lungs from either control or PB-treated rats

  10. Cluster-C1 observations on the geometrical structure of linear magnetic holes in the solar wind at 1 AU

    OpenAIRE

    Reme, H.; Lucek, E.; Liu, Z.X.; Sun, W. J.; L. Xie; Z. Y. Pu; Zong, Q. G.; Li, L.; S. Y. Fu; Zhang, T. L.; Shi, Q. Q.; Xiao, T.

    2010-01-01

    Interplanetary linear magnetic holes (LMHs) are structures in which the magnetic field magnitude decreases with little change in the field direction. They are a 10–30% subset of all interplanetary magnetic holes (MHs). Using magnetic field and plasma measurements obtained by Cluster-C1, we surveyed the LMHs in the solar wind at 1 AU. In total 567 interplanetary LMHs are identified from the magnetic field data when Cluster-C1 was in the solar wind from 2001 to 2004. We studied the relationship...

  11. Cluster-C1 observations on the geometrical structure of linear magnetic holes in the solar wind at 1 AU

    OpenAIRE

    Xiao, T.; Shi, Q. Q.; Zhang, T. L.; S. Y. Fu; Li, L.; Zong, Q. G.; Z. Y. Pu; L. Xie; Sun, W. J.; Liu, Z.X.; Lucek, E.; Reme, H.

    2010-01-01

    Interplanetary linear magnetic holes (LMHs) are structures in which the magnetic field magnitude decreases with little change in the field direction. They are a 10–30% subset of all interplanetary magnetic holes (MHs). Using magnetic field and plasma measurements obtained by Cluster-C1, we surveyed the LMHs in the solar wind at 1 AU. In total 567 interplanetary LMHs are identified from the magnetic field data when Cluster-C1 was in the solar wind from 2001 to 2004. We studie...

  12. An Atomic Force Microscopy Investigation of the Tracks Made by C+1-C+4 Bombardment on CR-39 Detectors

    Institute of Scientific and Technical Information of China (English)

    赵葵; 吴秀坤; 郭继宇; 隋丽; 梅俊平; 倪嵋楠; 包轶文

    2003-01-01

    Carbon micro-clusters are accelerated by an HI-13 tandem accelerator.The plastic nuclear track detectors CR-39are irradiated by C1-C4 beams from the HI-13 tandem accelerator and the tracks in CR-39 are studied using an atomic force microscope(AFM).The depths and diameters of C1-C4 tracks are measured for the first time in a nanometre scale.An enhancement of the energy loss is obtained for carbon clusters related to single carbon ions with the same velocity.The results show that the AFM observation is very useful in the quantitative analysis of clusters in the track detector CR-39.

  13. Structural Differences between the Streptococcus agalactiae Housekeeping and Pilus-Specific Sortases: SrtA and SrtC1

    OpenAIRE

    Khare, B.; Krishnan, V; Rajashankar, K. R.; I-Hsiu, H.; Xin, M.; Ton-That, H.; Narayana, S V

    2011-01-01

    The assembly of pili on the cell wall of Gram-positive bacteria requires transpeptidase enzymes called sortases. In Streptococcus agalactiae, the PI-1 pilus island of strain 2603V/R encodes two pilus-specific sortases (SrtC1 and SrtC2) and three pilins (GBS80, GBS52 and GBS104). Although either pilus-specific sortase is sufficient for the polymerization of the major pilin, GBS80, incorporation of the minor pilins GBS52 and GBS104 into the pilus structure requires SrtC1 and SrtC2, respectively...

  14. Allelic Diversification at the C (OsC1) Locus of Wild and Cultivated Rice: Nucleotide Changes Associated With Phenotypes

    OpenAIRE

    Saitoh, Kumi; Onishi, Kazumitsu; Mikami, Ichiho; Thidar, Khin; Sano, Yoshio

    2004-01-01

    Divergent phenotypes are often detected in domesticated plants despite the existence of invariant phenotypes in their wild forms. One such example in rice is the occurrence of varying degrees of apiculus coloration due to anthocyanin pigmentation, which was previously reported to be caused by a series of alleles at the C locus. The present study reveals, on the basis of comparison of its maps, that the C gene appears to be the rice homolog (OsC1) of maize C1, which belongs to the group of R2R...

  15. Hereditary Angioedema Due to C1 Inhibitor Deficiency in Serbia: Two Novel Mutations and Evidence of Genotype-Phenotype Association

    Science.gov (United States)

    Andrejević, Slađana; Korošec, Peter; Šilar, Mira; Košnik, Mitja; Mijanović, Radovan; Bonači-Nikolić, Branka; Rijavec, Matija

    2015-01-01

    Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is a rare autosomal dominant disease characterized by recurrent life-threatening oedemas and/or abdominal pain and caused by mutations affecting the C1 inhibitor gene, SERPING1. We sought to investigate the spectrum of SERPING1 mutations in Serbia and the possible genotype-phenotype association. C1-INH-HAE was diagnosed on the basis of clinical and laboratory criteria in 40 patients from 27 families; four were asymptomatic. Mutational analysis of the SERPING1 gene was performed by sequencing and multiplex ligation-dependent probe amplification. Disease-causing mutations in SERPING1 were identified in all patients. In C1-INH-HAE type I, we identified 19 different mutations, including 6 missense mutations, 6 nonsense mutations, 2 small deletions, 1 small insertion, 2 splicing defects and 2 large deletions. Two of the mutations (c.300C>T and c.1184_1185insTA) are reported here for the first time. All C1-INH-HAE type II patients from three families harboured the same substitution (c.1396C>T). Based on the type of mutation identified in the SERPING1 gene, patients were divided into two groups: group 1 (nonsense, frameshift, large deletions/insertions, splicing defect, and mutations at Arg444) or group 2 (missense, excluding mutations at Arg444). Significant differences were found in the clinical severity score (P = 0.005), prevalence of laryngeal (P = 0.040) and facial (P = 0.013) oedema, and long-term prophylaxis (P = 0.023) between the groups with different types of mutations. Because our population consisted of related subjects, differences in the severity score between mutation groups were further confirmed using the generalized estimating equation (P = 0.038). Our study identified 20 different disease-causing mutations, including two novel mutations, in all C1-INH-HAE patients, highlighting the heterogeneity of mutations in the SERPING1 gene. Furthermore, it appears that mutations with a clear effect

  16. Development and in-house validation of allergen-specific ELISA tests for the quantification of Dau c 1.01, Dau c 1.02 and Dau c 4 in carrot extracts (Daucus carota)

    NARCIS (Netherlands)

    K. Foetisch; L. Dahl; B. Jansen; W.M. Becker; J. Lidholm; R. van Ree; H. Broll; S. Kaul; S. Vieths; T. Holzhauser

    2011-01-01

    Even though carrot allergy is common in Europe, the amount of different allergens in carrots is still unknown due to a lack of methods for quantitative allergen measurements. The current study aimed at the development of quantitative ELISA tests for the known carrot allergens, namely Dau c 1.01, Dau

  17. Primary structure of cucumber (Cucumis sativus) ascorbate oxidase deduced from cDNA sequence: homology with blue copper proteins and tissue-specific expression.

    OpenAIRE

    Ohkawa, J; Okada, N; Shinmyo, A; Takano, M.

    1989-01-01

    cDNA clones for ascorbate oxidase were isolated from a cDNA library made from cucumber (Cucumis sativus) fruit mRNA. The library was screened with synthetic oligonucleotides that encode the NH2-terminal sequence of this enzyme. Nucleotide sequence analysis of the cloned cDNA inserts revealed a 1761-base-pair open reading frame that encoded an NH2-terminal signal peptide of 33 amino acids and a mature enzyme of 554 amino acids (Mr, 62,258). The amino acid sequence deduced from nucleotide seque...

  18. Concentrations of carbonyl sulfide and hydrogen cyanide in the free upper troposphere and lower stratosphere deduced from ATMOS/Spacelab 3 infrared solar occultation spectra

    Science.gov (United States)

    Zander, R.; Rinsland, C. P.; Russell, J. M., III; Farmer, C. B.; Norton, R. H.

    1988-01-01

    This paper presents the results on the volume mixing ratio profiles of carbonyl sulfide and hydrogen cyanide, deduced from the spectroscopic analysis of IR solar absorption spectra obtained in the occultation mode with the Atmospheric Trace Molecule Spectroscopy (ATMOS) instrument during its mission aboard Spacelab 3. A comparison of the ATMOS measurements for both northern and southern latitudes with previous field investigations at low midlatitudes shows a relatively good agreement. Southern Hemisphere volume mixing ratio profiles for both molecules were obtained for the first time, as were the profiles for the Northern Hemisphere covering the upper troposphere and the lower stratosphere simultaneously.

  19. Nucleotide sequence of Phaseolus vulgaris L. alcohol dehydrogenase encoding cDNA and three-dimensional structure prediction of the deduced protein

    Science.gov (United States)

    Amelia, Kassim; Khor, Chin Yin; Shah, Farida Habib; Bhore, Subhash J.

    2015-01-01

    Background: Common beans (Phaseolus vulgaris L.) are widely consumed as a source of proteins and natural products. However, its yield needs to be increased. In line with the agenda of Phaseomics (an international consortium), work of expressed sequence tags (ESTs) generation from bean pods was initiated. Altogether, 5972 ESTs have been isolated. Alcohol dehydrogenase (AD) encoding gene cDNA was a noticeable transcript among the generated ESTs. This AD is an important enzyme; therefore, to understand more about it this study was undertaken. Objective: The objective of this study was to elucidate P. vulgaris L. AD (PvAD) gene cDNA sequence and to predict the three-dimensional (3D) structure of deduced protein. Materials and Methods: positive and negative strands of the PvAD cDNA clone were sequenced using M13 forward and M13 reverse primers to elucidate the nucleotide sequence. Deduced PvAD cDNA and protein sequence was analyzed for their basic features using online bioinformatics tools. Sequence comparison was carried out using bl2seq program, and tree-view program was used to construct a phylogenetic tree. The secondary structures and 3D structure of PvAD protein were predicted by using the PHYRE automatic fold recognition server. Results: The sequencing results analysis showed that PvAD cDNA is 1294 bp in length. It's open reading frame encodes for a protein that contains 371 amino acids. Deduced protein sequence analysis showed the presence of putative substrate binding, catalytic Zn binding, and NAD binding sites. Results indicate that the predicted 3D structure of PvAD protein is analogous to the experimentally determined crystal structure of s-nitrosoglutathione reductase from an Arabidopsis species. Conclusions: The 1294 bp long PvAD cDNA encodes for 371 amino acid long protein that contains conserved domains required for biological functions of AD. The predicted deduced PvAD protein's 3D structure reflects the analogy with the crystal structure of

  20. Mutation analysis of ATP2C1 gene in patients with Hailey-Hailey disease%家族性良性天疱疮ATP2C1基因突变研究

    Institute of Scientific and Technical Information of China (English)

    颜潇潇; 田洪青; 于永翔; 王广进; 施仲香; 张福仁

    2010-01-01

    Objective To detect the mutations in ATP2C1 gene of 5 sporadic patients with Hailey-Hailey disease (HHD).Methods Five sporadic patients with HHD collected from the outpatient clinic setting were recruited into this study with informed consent.Blood samples were taken from all patients and 100 unrelated human controls.and DNA was extracted from these samples.Mutation scanning was carried out for ATP2C1 gene by polymerase chain reaction (PCR) and direct sequencing.Results The diagnosis of all cases was confirmed by typical clinical manifestation,cutaneous pathology and immunofluorescence pathology.Five novel mutations.including a deletion mutation (2025delG),three missence mutations (L269R,C348R,A651D) and a non-sense mutation (Q259X) were identified in these cases.No mutations were detected in any of the 100 controls.Conclusion Five novel mutations in ATP2C1 gene have been identified for Hailey-Hailey disease.%目的 探讨家族性良性天疱疮5个散发病例的ATP2C1基因突变.方法 5例来自门诊的散发病例,采集外周血,提取基因组DNA,采用PCR和DNA直接测序的方法,检测5个散发家族性良性天疱疮患者的ATP2C1基因突变,在100例正常人对照中予以验证.结果在5例具有典型临床表现,经皮肤病理和免疫病理确诊的散发家族性良性天疱疮患者,检测到5个未曾报道的ATP2C1基因突变位点,包括1个缺失突变(2025delG),3个错义突变(L269R,C348R,A651D),和1个无义突变(Q259x).100例正常人对照中均未检测到上述突变.结论 发现家族性良性天疱疮新的ATP2C1基因突变位点.

  1. Measurement of the η{sub c}(1S) production cross-section in proton–proton collisions via the decay η{sub c}(1S) → pp{sup -bar}

    Energy Technology Data Exchange (ETDEWEB)

    Aaij, R. [Nikhef National Institute for Subatomic Physics, Amsterdam (Netherlands); Beteta, C. Abellán [Physik-Institut, Universität Zürich, Zurich (Switzerland); Adeva, B. [Universidad de Santiago de Compostela, Santiago de Compostela (Spain); Adinolfi, M. [H.H. Wills Physics Laboratory, University of Bristol, Bristol (United Kingdom); Affolder, A. [Oliver Lodge Laboratory, University of Liverpool, Liverpool (United Kingdom); and others

    2015-07-04

    The production of the η{sub c}(1S) state in proton-proton collisions is probed via its decay to the pp{sup -bar} final state with the LHCb detector, in the rapidity range 2.06.5 GeV/c. The cross-section for prompt production of η{sub c}(1S) mesons relative to the prompt J/ψ cross-section is measured, for the first time, to be σ{sub η{sub c(1S)}}/σ{sub J/ψ}=1.74 ± 0.29 ± 0.28 ± 0.18{sub B} at a centre-of-mass energy √s=7 TeV using data corresponding to an integrated luminosity of 0.7 fb{sup -1}, and σ{sub η{sub c(1S)}}/σ{sub J/ψ}=1.60±0.29±0.25±0.17{sub B} at √s=8 TeV using 2.0 fb{sup -1}. The uncertainties quoted are, in order, statistical, systematic, and that on the ratio of branching fractions of the η{sub c}(1S) and J/ψ decays to the pp{sup -bar} final state. In addition, the inclusive branching fraction of b-hadron decays into η{sub c}(1S) mesons is measured, for the first time, to be B(b→η{sub c}X)=(4.88 ± 0.64 ± 0.29 ± 0.67{sub B})×10{sup -3}, where the third uncertainty includes also the uncertainty on the J/ψ inclusive branching fraction from b-hadron decays. The difference between the J/ψ and η{sub c}(1S) meson masses is determined to be 114.7±1.5±0.1 MeV /c{sup 2}.

  2. Measurement of the η{sub c}(1S) production cross-section in proton-proton collisions via the decay η{sub c}(1S) → p anti p

    Energy Technology Data Exchange (ETDEWEB)

    Aaij, R. [Nikhef National Institute for Subatomic Physics, Amsterdam (Netherlands); Beteta, C.A. [Universitaet Zuerich, Physik-Institut, Zurich (Switzerland); Adeva, B. [Universidad de Santiago de Compostela, Santiago de Compostela (Spain); and others

    2015-07-15

    The production of the η{sub c}(1S) state in proton-proton collisions is probed via its decay to the p anti p final state with the LHCb detector, in the rapidity range 2.0 < y < 4.5 and in the meson transverse-momentum range p{sub T} > 6.5 GeV/c. The cross-section for prompt production of η{sub c}(1S) mesons relative to the prompt J/ψ cross-section is measured, for the first time, to be σ{sub η{sub c(1S)}}/σ{sub J/ψ} = 1.74 ± 0.29 ± 0.28 ± 0.18{sub B} at a centre-of-mass energy √(s) = 7 TeV using data corresponding to an integrated luminosity of 0.7 fb{sup -1}, and σ{sub η{sub c(1S)}}/σ{sub J/ψ} = 1.60 ± 0.29 ± 0.25 ± 0.17{sub B} at √(s) = 8 TeV using 2.0 fb{sup -1}. The uncertainties quoted are, in order, statistical, systematic, and that on the ratio of branching fractions of the η{sub c}(1S) and J/ψ decays to the p anti p final state. In addition, the inclusive branching fraction of b-hadron decays into η{sub c}(1S) mesons is measured, for the first time, to be B(b → η{sub c}X) = (4.88 ± 0.64 ± 0.29 ± 0.67{sub B}) x 10{sup -3}, where the third uncertainty includes also the uncertainty on the J/ψ inclusive branching fraction from b-hadron decays. The difference between the J/ψ and η{sub c}(1S) meson masses is determined to be 114.7 ± 1.5 ± 0.1 MeV/c{sup 2}. (orig.)

  3. 40 CFR Figure C-1 to Subpart C of... - Suggested Format for Reporting Test Results for Methods for SO 2, CO, O 3, NO 2

    Science.gov (United States)

    2010-07-01

    ... Results for Methods for SO 2, CO, O 3, NO 2 C Figure C-1 to Subpart C of Part 53 Protection of Environment... Pt. 53, Subpt. C, Fig. C-1 Figure C-1 to Subpart C of Part 53—Suggested Format for Reporting Test... Difference Table C-1 spec. Pass or fail Low 1 ____ ppm 2 to ____ ppm 3 4 5 6 Medium 1 ____ ppm 2 to ____...

  4. A case of tongue edema associated with radiation-induced ulcer with low level of C1 inhibitor activity

    International Nuclear Information System (INIS)

    A 66-year-old man became aware of sudden swelling of the tongue with swallowing disturbance. He had a medical history of tongue cancer treated by interstitial radiotherapy and had undergone a cytological examination of an ulcer on the right side of the tongue three weeks earlier because of suspected recurrence. The cytological examination result was class I with no malignant findings. Angioneurotic edema, so-called ''Quincke's edema'', associated with radiation-induced ulcer of the tongue, was diagnosed. Tranexamic acid, d-chlorpheniramine maleate, and epinephrine were administered. After six days, the tongue edema had almost disappeared. Laboratory examination revealed a low level of C1 inhibitor activity with normal levels of CH50, C1, C3, and C4 at the time of swelling. Hereditary angioneurotic edema with absence of hereditary trait was suspected based on the sudden edema attack and low level of C1 inhibitor activity. The C1 inhibitor activity returned to normal after disappearance of the tongue edema. (author)

  5. Observation of chi(c1) Decays into Vector Meson Pairs phi phi, omega omega, and omega phi

    NARCIS (Netherlands)

    Ablikim, M.; Achasov, M. N.; An, L.; An, Q.; An, Z. H.; Bai, J. Z.; Baldini, R.; Ban, Y.; Becker, J.; Berger, N.; Bertani, M.; Bian, J. M.; Bondarenko, O.; Boyko, I.; Briere, R. A.; Bytev, V.; Cai, X.; Cao, G. F.; Cao, X. X.; Chang, J. F.; Chelkov, G.; Chen, G.; Chen, H. S.; Chen, J. C.; Chen, M. L.; Chen, S. J.; Chen, Y.; Chen, Y. B.; Cheng, H. P.; Chu, Y. P.; Cronin-Hennessy, D.; Dai, H. L.; Dai, J. P.; Dedovich, D.; Deng, Z. Y.; Denysenko, I.; Destefanis, M.; Ding, Y.; Dong, L. Y.; Dong, M. Y.; Du, S. X.; Duan, M. Y.; Fan, R. R.; Fang, J.; Fang, S. S.; Feng, C. Q.; Fu, C. D.; Fu, J. L.; Gao, Y.; Geng, C.; Goetzen, K.; Gong, W. X.; Greco, M.; Grishin, S.; Gu, M. H.; Gu, Y. T.; Guan, Y. H.; Guo, A. Q.; Guo, L. B.; Guo, Y. P.; Hao, X. Q.; Harris, F. A.; He, K. L.; He, M.; He, Z. Y.; Heng, Y. K.; Hou, Z. L.; Hu, H. M.; Hu, J. F.; Hu, T.; Huang, B.; Huang, G. M.; Huang, J. S.; Huang, X. T.; Huang, Y. P.; Hussain, T.; Ji, C. S.; Ji, Q.; Ji, X. B.; Ji, X. L.; Jia, L. K.; Jiang, L. L.; Jiang, X. S.; Jiao, J. B.; Jiao, Z.; Jin, D. P.; Jin, S.; Jing, F. F.; Kavatsyuk, M.; Komamiya, S.; Kuehn, W.; Lange, J. S.; Leung, J. K. C.; Li, Cheng; Li, Cui; Li, D. M.; Li, F.; Li, G.; Li, H. B.; Li, J. C.; Li, Lei; Li, N. B.; Li, Q. J.; Li, W. D.; Li, W. G.; Li, X. L.; Li, X. N.; Li, X. Q.; Li, X. R.; Li, Z. B.; Liang, H.; Liang, Y. F.; Liang, Y. T.; Liao, G. R.; Liao, X. T.; Liu, B. J.; Liu, B. J.; Liu, C. L.; Liu, C. X.; Liu, C. Y.; Liu, F. H.; Liu, Fang; Liu, Feng; Liu, G. C.; Liu, H.; Liu, H. B.; Liu, H. M.; Liu, H. W.; Liu, J. P.; Liu, K.; Liu, K. Y.; Liu, Q.; Liu, S. B.; Liu, X.; Liu, X. H.; Liu, Y. B.; Liu, Y. W.; Liu, Yong; Liu, Z. A.; Liu, Z. Q.; Loehner, H.; Lu, G. R.; Lu, H. J.; Lu, J. G.; Lu, Q. W.; Lu, X. R.; Lu, Y. P.; Luo, C. L.; Luo, M. X.; Luo, T.; Luo, X. L.; Ma, C. L.; Ma, F. C.; Ma, H. L.; Ma, Q. M.; Ma, T.; Ma, X.; Ma, X. Y.; Maggiora, M.; Malik, Q. A.; Mao, H.; Mao, Y. J.; Mao, Z. P.; Messchendorp, J. G.; Min, J.; Mitchell, R. E.; Mo, X. H.; Muchnoi, N. Yu.; Nefedov, Y.; Ning, Z.; Olsen, S. L.; Ouyang, Q.; Pacetti, S.; Pelizaeus, M.; Peters, K.; Ping, J. L.; Ping, R. G.; Poling, R.; Pun, C. S. J.; Qi, M.; Qian, S.; Qiao, C. F.; Qin, X. S.; Qiu, J. F.; Rashid, K. H.; Rong, G.; Ruan, X. D.; Sarantsev, A.; Schulze, J.; Shao, M.; Shen, C. P.; Shen, X. Y.; Sheng, H. Y.; Shepherd, M. R.; Song, X. Y.; Sonoda, S.; Spataro, S.; Spruck, B.; Sun, D. H.; Sun, G. X.; Sun, J. F.; Sun, S. S.; Sun, X. D.; Sun, Y. J.; Sun, Y. Z.; Sun, Z. J.; Sun, Z. T.; Tang, C. J.; Tang, X.; Tang, X. F.; Tian, H. L.; Toth, D.; Varner, G. S.; Wan, X.; Wang, B. Q.; Wang, K.; Wang, L. L.; Wang, L. S.; Wang, M.; Wang, P.; Wang, P. L.; Wang, Q.; Wang, S. G.; Wang, X. L.; Wang, Y. D.; Wang, Y. F.; Wang, Y. Q.; Wang, Z.; Wang, Z. G.; Wang, Z. Y.; Wei, D. H.; Wen, Q. G.; Wen, S. P.; Wiedner, U.; Wu, L. H.; Wu, N.; Wu, W.; Wu, Z.; Xiao, Z. J.; Xie, Y. G.; Xu, G. F.; Xu, G. M.; Xu, H.; Xu, Y.; Xu, Z. R.; Xu, Z. Z.; Xue, Z.; Yan, L.; Yan, W. B.; Yan, Y. H.; Yang, H. X.; Yang, M.; Yang, T.; Yang, Y.; Yang, Y. X.; Ye, M.; Ye, M. H.; Yu, B. X.; Yu, C. X.; Yu, L.; Yuan, C. Z.; Yuan, W. L.; Yuan, Y.; Zafar, A. A.; Zallo, A.; Zeng, Y.; Zhang, B. X.; Zhang, B. Y.; Zhang, C. C.; Zhang, D. H.; Zhang, H. H.; Zhang, H. Y.; Zhang, J.; Zhang, J. W.; Zhang, J. Y.; Zhang, J. Z.; Zhang, L.; Zhang, S. H.; Zhang, T. R.; Zhang, X. J.; Zhang, X. Y.; Zhang, Y.; Zhang, Y. H.; Zhang, Z. P.; Zhang, Z. Y.; Zhao, G.; Zhao, H. S.; Zhao, Jiawei; Zhao, Jingwei; Zhao, Lei; Zhao, Ling; Zhao, M. G.; Zhao, Q.; Zhao, S. J.; Zhao, T. C.; Zhao, X. H.; Zhao, Y. B.; Zhao, Z. G.; Zhao, Z. L.; Zhemchugov, A.; Zheng, B.; Zheng, J. P.; Zheng, Y. H.; Zheng, Z. P.; Zhong, B.; Zhong, J.; Zhong, L.; Zhou, L.; Zhou, X. K.; Zhou, X. R.; Zhu, C.; Zhu, K.; Zhu, K. J.; Zhu, S. H.; Zhu, X. L.; Zhu, X. W.; Zhu, Y. S.; Zhu, Z. A.; Zhuang, J.; Zou, B. S.; Zou, J. H.; Zuo, J. X.; Zweber, P.

    2011-01-01

    Using (106 +/- 4) x 10(6) psi(3686) events accumulated with the BESIII detector at the BEPCII e(+) e(-) collider, we present the first measurement of decays of chi(c1) to vector meson pairs phi phi, omega omega, and omega phi. The branching fractions are measured to be (4.4 +/- 0.3 +/- 0.5) x 10(-4)

  6. The comparative pathology of the glycosidase inhibitors swainsonine, castanospermine, calystegines A3, B2 and C1 in mice

    Science.gov (United States)

    To characterize and compare the toxicity and pathology of glycosidase inhibitors swainsonine, castanospermine, calystegine A3, calystegine B2 and calystegine C1, 48 Swiss Webster, male mice were randomly divided into 16 groups of 3 animals each. All mice were implanted with subcutaneous osmotic min...

  7. Proteolysis of the heavy chain of major histocompatibility complex class I antigens by complement component C1s

    DEFF Research Database (Denmark)

    Eriksson, H; Nissen, Mogens Holst

    1990-01-01

    into at least two fragments, with apparent molecular weights of 22,000 and 24,000 g/mol on sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), under both reducing and non-reducing conditions. The cleavage of the heavy chain is inhibited by the presence of C1 esterase inhibitor. The......The major histocompatibility complex (MHC) class I antigens contain a light chain, beta 2-microglobulin, non-covalently associated to the transmembrane heavy alpha-chain carrying the allotypic determinants. Since the C1q complement component is known to associate with beta 2-microglobulin, and we...... mouse MHC class II antigen (I-Ad). Mouse MHC class I antigen-specific determinants could also be detected in supernatant from mouse spleen cells incubated with C1r and C1s. These results indicate the presence in the body fluids of a non-membrane-bound soluble form of the alpha 1-and alpha 2-domains...

  8. 12 CFR 225.104 - “Services” under section 4(c)(1) of Bank Holding Company Act.

    Science.gov (United States)

    2010-01-01

    ... company chooses to have done through another organization. Moreover, the report of the Senate Banking and... Holding Company Act. 225.104 Section 225.104 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF... Holding Company Act. (a) Section 4(c)(1) of the Bank Holding Company Act, among other things, exempts...

  9. New Views of Southern Nearside Lunar Highland Composition from the Chandrayaan-1 X-ray Spectrometer (C1XS)

    Science.gov (United States)

    Athiray, P. S.; Narendranath, S.; Sreekumar, P.; C1XS Team

    2016-05-01

    Lunar surface elemental abundances - Results from Chandrayaan-1 X-ray Spectrometer (C1XS) on-board Chandrayaan-1 and goals for the upcoming Chandrayaan-2 Large Area Soft X-ray Spectrometer (CLASS) experiment on-board Chandrayaan-2.

  10. The M3D-C1 Approach to Simulating 3D 2-fluid Magnetohydrodynamics in Magnetic Fusion Experiments

    International Nuclear Information System (INIS)

    A new approach for solving the 3D MHD equations in a strongly magnetized toroidal plasma is presented which uses high-order 2D finite elements with C1 continuity. The vector fields use a physics-based decomposition. An efficient implicit time advance separates the velocity and field advance. ITAPS (SCOREC) adaptivity software and TOPS solvers are used

  11. 76 FR 39254 - Airworthiness Directives; Schweizer Aircraft Corporation (Schweizer) Model 269A, A-1, B, C, C-1...

    Science.gov (United States)

    2011-07-06

    ... Regulatory Policies and Procedures (44 FR 11034, February 26, 1979), (3) Will not affect intrastate aviation... Corporation (Schweizer) Model 269A, A-1, B, C, C-1, and TH-55 Series Helicopters AGENCY: Federal Aviation... reviewed Schweizer Service Bulletins No. B-295 for Model 269A, A-1, B, and C helicopters, and No....

  12. Transient Solution of the M/M/C1 Queue with Additional C2 Servers for Longer Queues and Balking

    Directory of Open Access Journals (Sweden)

    R. O. Al-Seedy

    2008-01-01

    Full Text Available The goal of this research is to discuss the M/M/C1 queue with additional C2 servers for longer queues and balking. By using generating function technique the transient probabilities are derived in terms of the modified Bessel function.

  13. Exponential decay of correlations for nonuniformly hyperbolic flows with a C^{1+\\alpha} stable foliation, including the classical Lorenz attractor

    OpenAIRE

    Araújo, Vitor; Melbourne, Ian

    2015-01-01

    We prove exponential decay of correlations for a class of $C^{1+\\alpha}$ uniformly hyperbolic skew product flows, subject to a uniform nonintegrability condition. In particular, this establishes exponential decay of correlations for an open set of geometric Lorenz attractors. As a special case, we show that the classical Lorenz attractor is robustly exponentially mixing.

  14. Epigenetic Regulation of Placental "NR3C1": Mechanism Underlying Prenatal Programming of Infant Neurobehavior by Maternal Smoking?

    Science.gov (United States)

    Stroud, Laura R.; Papandonatos, George D.; Salisbury, Amy L.; Phipps, Maureen G.; Huestis, Marilyn A.; Niaura, Raymond; Padbury, James F.; Marsit, Carmen J.; Lester, Barry M.

    2016-01-01

    Epigenetic regulation of the placental glucocorticoid receptor gene ("NR3C1") was investigated as a mechanism underlying links between maternal smoking during pregnancy (MSDP) and infant neurobehavior in 45 mother-infant pairs (49% MSDP-exposed; 52% minorities; ages 18-35). The Neonatal Intensive Care Unit (NICU) Network Neurobehavioral…

  15. The Levels of the Lectin Pathway Serine Protease MASP-1 and Its Complex Formation with C1 Inhibitor Are Linked to the Severity of Hereditary Angioedema

    DEFF Research Database (Denmark)

    Hansen, Cecilie Bo; Csuka, Dorottya; Munthe-Fog, Lea; Varga, Lilian; Farkas, Henriette; Hansen, Karin Møller; Koch, Claus; Skjødt, Karsten; Garred, Peter; Skjoedt, Mikkel-Ole

    2015-01-01

    C1 inhibitor (C1-INH) is known to form complexes with the lectin complement pathway serine proteases MASP-1 and MASP-2. Deficiency of C1-INH is associated with hereditary angioedema (HAE), an autosomal inherited disease characterized by swelling attacks caused by elevated levels of bradykinin. MASP...

  16. Structural Differences between the Streptococcus agalactiae Housekeeping and Pilus-Specific Sortases: SrtA and SrtC1

    Energy Technology Data Exchange (ETDEWEB)

    Khare, B.; Krishnan, V.; Rajashankar, K.R.; I-Hsiu, H.; Xin, M.; Ton-That, H.; Narayana, S.V. (Texas-HSC); (Cornell); (UAB)

    2011-10-21

    The assembly of pili on the cell wall of Gram-positive bacteria requires transpeptidase enzymes called sortases. In Streptococcus agalactiae, the PI-1 pilus island of strain 2603V/R encodes two pilus-specific sortases (SrtC1 and SrtC2) and three pilins (GBS80, GBS52 and GBS104). Although either pilus-specific sortase is sufficient for the polymerization of the major pilin, GBS80, incorporation of the minor pilins GBS52 and GBS104 into the pilus structure requires SrtC1 and SrtC2, respectively. The S. agalactiae housekeeping sortase, SrtA, whose gene is present at a different location and does not catalyze pilus polymerization, was shown to be involved in cell wall anchoring of pilus polymers. To understand the structural basis of sortases involved in such diverse functions, we determined the crystal structures of S. agalactiae SrtC1 and SrtA. Both enzymes are made of an eight-stranded beta-barrel core with variations in their active site architecture. SrtA exhibits a catalytic triad arrangement similar to that in Streptococcus pyogenes SrtA but different from that in Staphylococcus aureus SrtA. In contrast, the SrtC1 enzyme contains an N-terminal helical domain and a 'lid' in its putative active site, which is similar to that seen in Streptococcus pneumoniae pilus-specific sortases, although with subtle differences in positioning and composition. To understand the effect of such differences on substrate recognition, we have also determined the crystal structure of a SrtC1 mutant, in which the conserved DP(W/F/Y) motif was replaced with the sorting signal motif of GBS80, IPNTG. By comparing the structures of WT wild type SrtA and SrtC1 and the 'lid' mutant of SrtC1, we propose that structural elements within the active site and the lid may be important for defining the role of specific sortase in pili biogenesis.

  17. Structural differences between the Streptococcus agalactiae housekeeping and pilus-specific sortases: SrtA and SrtC1.

    Directory of Open Access Journals (Sweden)

    B Khare

    Full Text Available The assembly of pili on the cell wall of Gram-positive bacteria requires transpeptidase enzymes called sortases. In Streptococcus agalactiae, the PI-1 pilus island of strain 2603V/R encodes two pilus-specific sortases (SrtC1 and SrtC2 and three pilins (GBS80, GBS52 and GBS104. Although either pilus-specific sortase is sufficient for the polymerization of the major pilin, GBS80, incorporation of the minor pilins GBS52 and GBS104 into the pilus structure requires SrtC1 and SrtC2, respectively. The S. agalactiae housekeeping sortase, SrtA, whose gene is present at a different location and does not catalyze pilus polymerization, was shown to be involved in cell wall anchoring of pilus polymers. To understand the structural basis of sortases involved in such diverse functions, we determined the crystal structures of S. agalactiae SrtC1 and SrtA. Both enzymes are made of an eight-stranded beta-barrel core with variations in their active site architecture. SrtA exhibits a catalytic triad arrangement similar to that in Streptococcus pyogenes SrtA but different from that in Staphylococcus aureus SrtA. In contrast, the SrtC1 enzyme contains an N-terminal helical domain and a 'lid' in its putative active site, which is similar to that seen in Streptococcus pneumoniae pilus-specific sortases, although with subtle differences in positioning and composition. To understand the effect of such differences on substrate recognition, we have also determined the crystal structure of a SrtC1 mutant, in which the conserved DP(W/F/Y motif was replaced with the sorting signal motif of GBS80, IPNTG. By comparing the structures of WT wild type SrtA and SrtC1 and the 'lid' mutant of SrtC1, we propose that structural elements within the active site and the lid may be important for defining the role of specific sortase in pili biogenesis.

  18. A Hypothesis: Life Initiated from Two Genes, as Deduced from the RNA World Hypothesis and the Characteristics of Life-Like Systems

    Directory of Open Access Journals (Sweden)

    Kunio Kawamura

    2016-08-01

    Full Text Available RNA played a central role in the emergence of the first life-like system on primitive Earth since RNA molecules contain both genetic information and catalytic activity. However, there are several drawbacks regarding the RNA world hypothesis. Here, I briefly discuss the feasibility of the RNA world hypothesis to deduce the RNA functions that are essential for forming a life-like system. At the same time, I have conducted a conceptual analysis of the characteristics of biosystems as a useful approach to deduce a realistic life-like system in relation to the definition of life. For instance, an RNA-based life-like system should possess enough stability to resist environmental perturbations, by developing a cell-like compartment, for instance. Here, a conceptual viewpoint is summarized to provide a realistic life-like system that is compatible with the primitive Earth environment and the capabilities of RNA molecules. According to the empirical and conceptual analysis, I propose the hypothesis that the first life-like system could have initiated from only two genes.

  19. Tomographic analysis of data from the JET neutron profile monitor to deduce the 2-D spatial and temporal evolution of neutron emissivity

    International Nuclear Information System (INIS)

    Measurements from the JET neutron profile monitor are analyzed tomographically to deduce the two-dimensional spatial distribution of neutron emissivity and its temporal evolution. The most dramatic change in the emissivity profile is produced by a sawtooth crash. The profiles before and after a sawtooth crash are determined and changes in their characteristics, such as width and amplitude, are compared to those deduced from other diagnostics, including soft X-rays, electron density interferometers and electron cyclotron emission. The drop in the central neutron emissivity can be much larger than that obtained from the integrated global neutron emission, and hollow emissivity profiles are produced. The observed inversion radius is the same on neutron, soft X-ray, and electron temperature profiles. This hollow profile can be understood by observations of the soft X-ray emissivity on the fastest time-scale. A major theme of this paper is that much more information and understanding can be gained if several diagnostics are used together, with their different resolutions, time-scales and physical properties measured. (author). 12 refs, 5 figs

  20. Atmospheric CO2 variations over the last three glacial-interglacial climatic cycles deduced from the Dome Fuji deep ice core, Antarctica using a wet extraction technique

    International Nuclear Information System (INIS)

    A deep ice core drilled at Dome Fuji, East Antarctica was analyzed for the CO2 concentration using a wet extraction method in order to reconstruct its atmospheric variations over the past 320 kyr, which includes three full glacial-interglacial climatic cycles, with a mean time resolution of about 1.1 kyr. The CO2 concentration values derived for the past 65 kyr are very close to those obtained from other Antarctic ice cores using dry extraction methods, although the wet extraction method is generally thought to be inappropriate for the determination of the CO2 concentration. The comparison between the CO2 and Ca2+ concentrations deduced from the Dome Fuji core suggests that calcium carbonate emitted from lands was mostly neutralized in the atmosphere before reaching the central part of Antarctica, or that only a small part of calcium carbonate was involved in CO2 production during the wet extraction process. The CO2 concentration for the past 320 kyr deduced from the Dome Fuji core varies between 190 and 300 ppmv, showing clear glacial-interglacial variations similar to the result of the Vostok ice core. However, for some periods, the concentration values of the Dome Fuji core are higher by up to 20 ppmv than those of the Vostok core. There is no clear indication that such differences are related to variations of chemical components of Ca2+, microparticle and acidity of the Dome Fuji core

  1. Evolutionary Steps in the Emergence of Life Deduced from the Bottom-Up Approach and GADV Hypothesis (Top-Down Approach

    Directory of Open Access Journals (Sweden)

    Kenji Ikehara

    2016-01-01

    Full Text Available It is no doubt quite difficult to solve the riddle of the origin of life. So, firstly, I would like to point out the kinds of obstacles there are in solving this riddle and how we should tackle these difficult problems, reviewing the studies that have been conducted so far. After that, I will propose that the consecutive evolutionary steps in a timeline can be rationally deduced by using a common event as a juncture, which is obtained by two counter-directional approaches: one is the bottom-up approach through which many researchers have studied the origin of life, and the other is the top-down approach, through which I established the [GADV]-protein world hypothesis or GADV hypothesis on the origin of life starting from a study on the formation of entirely new genes in extant microorganisms. Last, I will describe the probable evolutionary process from the formation of Earth to the emergence of life, which was deduced by using a common event—the establishment of the first genetic code encoding [GADV]-amino acids—as a juncture for the results obtained from the two approaches.

  2. Scrapie pathogenesis: the role of complement C1q in scrapie agent uptake by conventional dendritic cells.

    Science.gov (United States)

    Flores-Langarica, Adriana; Sebti, Yasmine; Mitchell, Daniel A; Sim, Robert B; MacPherson, Gordon G

    2009-02-01

    Mice lacking complement components show delayed development of prion disease following peripheral inoculation. The delay could relate to reduced scrapie prion protein (PrP(Sc)) accumulation on follicular dendritic cells (DCs). However conventional DCs (cDCs) play a crucial role in the early pathogenesis of prion diseases and complement deficiency could result in decreased PrP(Sc) uptake by cDCs in the periphery. To explore this possibility, we cultured murine splenic or gut-associated lymph node cDCs with scrapie-infected whole brain homogenate in the presence or absence of complement. Uptake decreased significantly if the serum in the cultures was heat-inactivated. Because heat inactivation primarily denatures C1q, we used serum from C1q(-/-) mice and showed that PrP(Sc) uptake was markedly decreased. PrP(Sc) internalization was saturable and temperature-dependent, suggesting receptor-mediated uptake. Furthermore, uptake characteristics differed from fluid-phase endocytosis. Immunofluorescence showed colocalization of C1q and PrP(Sc), suggesting interaction between these molecules. We evaluated the expression of several complement receptors on cDCs and confirmed that cDCs that take up PrP(Sc) express one of the C1q receptors, calreticulin. Our results show that C1q participates in PrP(Sc) uptake by cDCs, revealing a critical role for cDCs in initial prion capture, an event that takes place before the PrP(Sc) accumulation within the follicular DC network. PMID:19155476

  3. Comparison of gene expression profiles of HepG2 cells exposed to Crambescins C1 and A1

    Directory of Open Access Journals (Sweden)

    María R. Sánchez

    2014-06-01

    Full Text Available Crambescins are guanidine alkaloids firstly isolated in the early 90s from the encrusting Mediterranean sponge Crambe crambe (Schmidt, 1862 (Bondu et al., 2012, Laville et al., 2009, Berlinck et al., 1990. C. crambe derivatives are divided in two families named crambescins and crambescidins (Gerlinck et al., 1992. Although data on the bioactivity of these compounds is scarce, crambescidins have recognized cytotoxic, antifungal, antioxidant, antimicrobial and antiviral activities (Buscema and Van de Vyver, 1985, Jares-Erijman., 1998, Olszewski et al., 2004, Lazaro et al., 2006, Suna et al., 2007, AOKI et al., 2004. Recently we have carefully evaluated the cytotoxic activity of C816 over several human tumor cell types and characterized some of the cellular mechanisms responsible of the anti-proliferative effect of this compound on human liver-derived tumor cells (Rubiolo et al., 2013. Taking this into account, and to better understand the mechanism of action of crambescins and their potential as therapeutic agents, we made a comparative gene expression profiling of HepG2 cells after crambescin C1 (C1 and crambescin A1 (CA1 exposures. Results have shown that C1 induces genes involved in sterol and glucose metabolisms and metabolism involving growth factors. It also down regulates genes mainly involved in cell cycle control, DNA replication, recombination and repair, and drug metabolism. Flow cytometry assays revealed that C1 produces a G0/G1 arrest in HepG2 cell cycle progression. CA1 also down-regulates genes involved in cell cycle regulation, DNA recombination and pathways related to tumor cells proliferation with lower potency when compared to C1.

  4. gC1qR expression in chimpanzees with resolved and chronic infection: Potential role of HCV core/gC1qR-mediated T cell suppression in the outcome of HCV infection

    International Nuclear Information System (INIS)

    Chimpanzee is a unique animal model for HCV infection, in which about 50% of infections resolve spontaneously. It has been reported that the magnitude of T cell responses to HCV core in recovered chimpanzees is greater than that in chronically infected ones. However, the mechanism(s) by which the chimpanzees with resolved infection overcome core-mediated immunosuppression remains unknown. In this study, we examined the effect of HCV core on T cell responsiveness in chimpanzees with resolved and chronic HCV infection. We found that core protein strongly inhibited T cell activation and proliferation in chimpanzees with chronic infection, while this inhibition was limited in chimpanzees with resolved infection. Notably, the level of gC1qR, as well as the binding of core protein, on the surface of T cells was lower in recovered chimpanzees when compared to chimpanzees with chronic HCV infection. Intriguingly, the observed differences in gC1qR expression levels and susceptibility to core-induced suppression amongst HCV-chronically infected and recovered chimpanzees were observed prior to HCV challenge, suggesting a possible genetic determination of the outcome of infection. These findings suggest that gC1qR expression on the surface of T cells is crucial for HCV core-mediated T cell suppression and viral clearance, and that represents a novel mechanism by which a virus usurps host machinery for persistence

  5. DYX1C1基因rs3743205位点等位基因的功能研究%Function Research on DYX1C1 Gene rs3743205 Site Gene Alleles

    Institute of Scientific and Technical Information of China (English)

    王志超; 沈黎; 刘得水; 李丹; 吴桐; 赵阿勐; 崔光成

    2016-01-01

    目的:为鉴定儿童发展性阅读障碍发病相关易感基因DYX1C1的rs3743205位点-3C/T不同等位基因对基因调控区转录活性的影响。方法本研究构建含DYX1C1基因rs3743205位点-3C/T不同等位基因的萤光素酶报告基因重组质粒,体外转染原代培养神经细胞并测定其瞬时表达萤光素酶活性。结果体外转染增殖期原代培养神经细胞,含等位基因-3T重组质粒的报告基因荧光素酶表达活性高于含等位基因-3C重组质粒,并均低于PGL3-control Plas-mid。结论位于DYX1C1基因5'调控区的rs3743205位点-3T等位基因可能参与基因的转录调控,-3C等位基因可能是儿童发展性阅读障碍的易感基因。%Objective To identify the effect of children developmental dyslexia invasion susceptibility gene DYX1C1 rs3743205 site -3C/T different gene alleles on transcription activity in gene control region. Methods The luciferase reporter gene recombinant plasmid containing DYX1C1 gene rs3743205 site -3C/T different gene alleles was structured, and the nerve cells were primarily cultured transfection in vitro and the transcient expression of luciferase activity was measured. Results The nerve cells were primarily cultured in transfection in vitro multiplication period, the expression activity of lu-ciferase containing gene alleles -3T recombinant plasmid reporter gene is higher than that of the recombinant plasmid con-taining gene alleles -3C, and both were lower than that of PGL3-control plasmid. Conclusion The rs3743205 site -3T gene alleles in the gene alleles gene 5’ control region may participate in the gene transcriptional control, and -3C gene alleles may be the susceptibility genes of children developmental dyslexia.

  6. Sm@C1(153491)-C94: A missing isomer from Sm@C94 mono-metallofullerenes

    Science.gov (United States)

    Zhao, Pei; Guo, Yi-Jun; Zhao, Rui-Sheng; Zhao, Xiang

    2016-01-01

    The Sm-containing endohedral metallofullerene (EMF) Sm@C94 has been investigated by quantum chemical and statistical thermodynamic methods. Sm@C1(153491)-C94 and Sm@C3v(153493)-C94 which both satisfy the isolated-pentagon rule (IPR) are exposed to possess considerable thermodynamic stabilities within the fullerene-formation temperature region (500-3000 K). Sm@C3v(153493)-C94 has been indeed determined experimentally, and a novel structure, Sm@C1(153491)-C94, is reported for the first time. These two isomers are related by a single Stone-Wales transformation. Meanwhile, frontier molecular orbital, natural electron configuration, and Mayer bond order analyses were employed to uncover their electronic properties. In addition, their optical spectra were simulated to support experimental identification and characterization.

  7. [C1-C2 transarticular screw fixation of atlanto-axial instability with tetraparesis in rheumatoid patient--case report].

    Science.gov (United States)

    Chrzanowska, Anetta; Chrzanowski, Robert; Skura, Antoni

    2010-01-01

    A case of a 50-year-old patient with C1-C2 subluxation and concomitant neurological deficits in the course of rheumatoid arthritis has been described. In the article the diagnostic and therapeutic procedures, consisting mainly of surgical treatment, have been presented. Indications for the surgery were: a rapid disease progression observed during the last six months, and tetraparesis. The authors propose the choice of applied surgical technique by taking into account difficulties consequential to the anatomy of this region, as well as additional complications regarding the chronic inflammation process. The use of transarticular screw fixation method, together with concurrent spinal cord decompression allowed the stabilization of C1-C2 subluxation and improvement of the neurological state of the patient. PMID:21591367

  8. Strict convexity and C 1, α regularity of potential functions in optimal transportation under condition A3w

    Science.gov (United States)

    Chen, Shibing; Wang, Xu-Jia

    2016-01-01

    In this paper we prove the strict c-convexity and the C 1, α regularity for potential functions in optimal transportation under condition (A3w). These results were obtained by Caffarelli [1,3,4] for the cost c (x, y) =| x - y | 2, by Liu [11], Loeper [15], Trudinger and Wang [20] for costs satisfying the condition (A3). For costs satisfying the condition (A3w), the results have also been proved by Figalli, Kim, and McCann [6], assuming that the initial and target domains are uniformly c-convex, see also [21]; and by Guillen and Kitagawa [8], assuming the cost function satisfies A3w in larger domains. In this paper we prove the strict c-convexity and the C 1, α regularity assuming either the support of source density is compactly contained in a larger domain where the cost function satisfies A3w, or the dimension 2 ≤ n ≤ 4.

  9. Mutation analysis of ATP2C1 gene in Chinese families with Hailey-Hailey disease%家族性良性天疱疮患者ATP2C1基因突变研究

    Institute of Scientific and Technical Information of China (English)

    罗素菊; 李晓莉; 刘原君; 倪海洋; 李燕; 刘全忠

    2012-01-01

    Objective To detect the mutations in ATP2C1 gene in 3 Chinese Hailey-Hailey-disease (HHD) families and 1 sporadic HHD patient.Methods Three Chinese HHD families and 1 sporadic HHD patient were recruited into this study with informed consent.Blood samples were taken from the patients with HHD,unaffected individuals in the HHD families and 100 unrelated normal human controls.Genomic DNA was extracted from these blood samples.All the exons and exon-intron boundaries of the ATP2C1 gene were amplified by PCR followed by direct sequencing via dye-termination chemistry.Results Three novel missense mutations in ATP2C1 gene were identified,including a 2048 G→A mutation in exon 20 causing the substitution of arginine by lysine at position 619 in the patients from HHD family 1,853A→C mutation in exon 8 causing the substitution of threonine by proline at position 221 in the patients from family 2,and 2323T→C mutation in exon 23 causing the substitution of tyrosine by histidine at position 711.None of these mutations were found in patients from the HHD family 3,unaffected individuals from the HHD family 1 and 2,or the unrelated normal human controls.Conclusion Three novel missense mutations are identified in the ATP2C 1 gene of patients with HHD.%目的 探讨3个家族性良性天疱疮家系和1例散发患者的ATP2C1基因突变.方法 采取家系中患病成员外周血,应用外周血细胞DNA抽提、PCR扩增和DNA直接测序等方法检测ATP2C1基因突变情况,用反向测序验证突变,用100例无血缘关系个体作正常人对照.结果 在2个家族性良性天疱疮家系和1例散发患者中发现3个未曾报道的错义突变.家系1第20外显子2048位碱基G→A,导致错义突变R619K;家系2第8外显子853位碱基A→C,导致错义突变T221P;散发患者第23外显子2323位碱基T→C,导致错义突变Y711H.家系中非患病成员和100例无血缘关系正常人均未发现这些改变.在1个家族性良性天疱疮家系未

  10. RXFP1 is Targeted by Complement C1q Tumor Necrosis Factor-Related Factor 8 in Brain Cancer

    OpenAIRE

    Thanasupawat, Thatchawan; Glogowska, Aleksandra; Burg, Maxwell; Wong, G. William; Hoang-Vu, Cuong; Hombach-Klonisch, Sabine; Klonisch, Thomas

    2015-01-01

    The relaxin-like RXFP1 ligand–receptor system has important functions in tumor growth and tissue invasion. Recently, we have identified the secreted protein, CTRP8, a member of the C1q/tumor necrosis factor-related protein (CTRP) family, as a novel ligand of the relaxin receptor, RXFP1, with functions in brain cancer. Here, we review the role of CTRP members in cancers cells with particular emphasis on CTRP8 in glioblastoma.

  11. RXFP1 is Targeted by Complement C1q Tumor Necrosis Factor-Related Factor 8 in Brain Cancer.

    Science.gov (United States)

    Thanasupawat, Thatchawan; Glogowska, Aleksandra; Burg, Maxwell; Wong, G William; Hoang-Vu, Cuong; Hombach-Klonisch, Sabine; Klonisch, Thomas

    2015-01-01

    The relaxin-like RXFP1 ligand-receptor system has important functions in tumor growth and tissue invasion. Recently, we have identified the secreted protein, CTRP8, a member of the C1q/tumor necrosis factor-related protein (CTRP) family, as a novel ligand of the relaxin receptor, RXFP1, with functions in brain cancer. Here, we review the role of CTRP members in cancers cells with particular emphasis on CTRP8 in glioblastoma. PMID:26322020

  12. Docetaxel Hidrat Menghambat Proliferasi dan Metastasis Sel Kanker Oral SP-C1 melalui Induksi Protein Maspin

    Directory of Open Access Journals (Sweden)

    Supriatno Supriatno

    2013-07-01

    Full Text Available Human oral tongue cancer (SP-C1 is thought to be a high grade malignancy. Despite advances in surgery, radiotherapy, chemotherapy and combination therapy, prognosis and survival of patients with human tongue cancer have not significantly improved over the past several decades. Treatment options for recurrent or refractory tongue cancer are limited. Therefore, as a strategy for refractory cancer, anti-mitotic chemotherapy and its mechanisms are of considerable interest, including those using docetaxel hydrate for inducing maspin protein. In the current study, the mechanisms responsible for growth suppression and metastasis of SP-C1 by docetaxel hydrate through induction of maspin regulation were investigated. To evaluate in vitro cell proliferation and cell metastasis, MTT and out-growth assays were performed, respectively. Furthermore, the expression of maspin mediated by docetaxel hydrate was analysed by Western blotting. The results showed that treatment with 50 g/ml docetaxel hydrate significantly suppressed SP-C1 cell growth from day 1. Strong inhibition of metastasis of SP-C1 cells was also shown by treatment with 50 g/ml of docetaxel hydrate. Moreover, a significant induction of maspin regulation was detected in cells treated with 10 and 50 g/ml of docetaxel hydrate. However, the same protein level was demonstrated in -tubulin expression. These findings suggest that docetaxel hydrate may have potential for powerful anti-mitotic chemotherapy through induction of maspin regulation.DOI: 10.14693/jdi.v15i1.77

  13. The Construction of the Probe for Amylase Ⅱ Gene Cloning from Bacillus halodurans Strain 38C1-1

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Primers and probes were established according to the sequences of the alpha-amylase genes of Bacillus. halodurans C-125, Thermus sp. IM6501, B. stearothermophilus ET-1, and B. acidopullulytics. Primers were designed and a 0.2 kb DNA fragment was amplified, the fragment was successfully used for the detection of the amylase Ⅱ gene in a 2 842 bp region from Bacillus halodurans strain 38C1-1.

  14. Cholesterol oxidation products are sensitive and specific blood-based biomarkers for Niemann-Pick C1 disease

    OpenAIRE

    Porter, Forbes D.; Scherrer, David E.; Lanier, Michael H.; Langmade, S. Joshua; Molugu, Vasumathi; Gale, Sarah E.; Olzeski, Dana; Sidhu, Rohini; Dietzen, Dennis J.; Fu, Rao; Wassif, Christopher A.; Yanjanin, Nicole M.; Marso, Steven P.; House, John; Vite, Charles

    2010-01-01

    Niemann-Pick type C1 (NPC1) disease is a rare progressive neurodegenerative disorder characterized by endolysosomal cholesterol accumulation. Previous studies implicating oxidative stress in NPC1 disease pathogenesis raised the possibility that non-enzymatic formation of cholesterol oxidation products could serve as disease biomarkers. We measured these metabolites in the plasma and tissues of the Npc1−/− mouse model and found several cholesterol oxidation products that were elevated in Npc1−...

  15. Catalytic Z-Selective Cross-Metathesis in Complex Molecule Synthesis: A Convergent Stereoselective Route to Disorazole C1

    OpenAIRE

    Speed, Alexander W. H.; Mann, Tyler J.; O’Brien, Robert V.; Schrock, Richard R.; Hoveyda, Amir H.

    2014-01-01

    A convergent diastereo- and enantioselective total synthesis of anticancer and antifungal macrocyclic natural product disorazole C1 is reported. The central feature of the successful route is the application of catalytic Z-selective cross-metathesis (CM). Specifically, we illustrate that catalyst-controlled stereoselective CM can be performed to afford structurally complex Z-alkenyl–B(pin) as well as Z-alkenyl iodide compounds reliably, efficiently, and with high selectivity (pin = pinacolato...

  16. Complement protein C1q directs macrophage polarization and limits inflammasome activity during the uptake of apoptotic cells.

    OpenAIRE

    Benoit, Marie E; Clarke, Elizabeth V.; Morgado, Pedro; Fraser, Deborah A.; Tenner, Andrea J.

    2012-01-01

    Deficiency in C1q, the recognition component of the classical complement cascade and a pattern recognition receptor involved in apoptotic cell clearance, leads to lupus-like autoimmune diseases characterized by auto-antibodies to self proteins and aberrant innate immune cell activation likely due to impaired clearance of apoptotic cells. In this study, we developed an autologous system using primary human lymphocytes and human monocyte-derived macrophages (HMDMs) to characterize the effect of...

  17. A Family with Atypical Hailey Hailey Disease- Is There More to the Underlying Genetics than ATP2C1?

    OpenAIRE

    Nina van Beek; Aikaterini Patsatsi; Yask Gupta; Steffen Möller; Miriam Freitag; Susanne Lemcke; Andreas Recke; Detlef Zillikens; Enno Schmidt; Saleh Ibrahim

    2015-01-01

    The autosomal dominant Hailey Hailey disease (HHD) is caused by mutations in the ATP2C1 gene encoding for human secretory pathway Ca2+/Mn2+ ATPase protein (hSPCA1) in the Golgi apparatus. Clinically, HHD presents with erosions and hyperkeratosis predominantly in the intertrigines. Here we report an exome next generation sequencing (NGS) based analysis of ATPase genes in a Greek family with 3 HHD patients presenting with clinically atypical lesions mainly localized on the neck and shoulders. B...

  18. 意大利Hailey-Hailey病患者ATP2C1基因突变分析

    Institute of Scientific and Technical Information of China (English)

    Majore; S.; Biolcati; G.; Barboni; L.

    2006-01-01

    Hailey-Hailey病(HHD)是一种罕见的常染色体显性遗传性病,其特征为主要累及体表皱褶部位的复发性皮损。HHD是因ATP2C1基因杂合子突变所致,该基因编码人类分泌途径的Ca+/Mn+-ATP酶蛋白1(hSPCAl)。本文中,作者描述了对来自意大利的8例HHD患者的分子研究,并证实了8例患者中有7例出现散布于ATP2C1基因中的6种不同的突变。其中4种突变是新突变。本研究结果确认了ATP2C1基因具有高度的等位基因异质性,支持HHD是一种遗传同质性疾病的观点。进而,作者创建了一张表格以总结之前报导的ATP2C1基因突变,并依照人类基因组变异协会指南修订了某些名称(如必要)。

  19. The Effect of Nitrogen Enrichment on C1-Cycling Microorganisms and Methane Flux in Salt Marsh Sediments

    OpenAIRE

    Irina Catherine Irvine; Lucía eVivanco; Peris N. Bentley; Martiny, Jennifer B. H.

    2012-01-01

    Methane (CH4) flux from ecosystems is driven by C1-cycling microorganisms – the methanogens and the methylotrophs. Little is understood about what regulates these communities, complicating predictions about how global change drivers such as nitrogen enrichment will affect methane cycling. Using a nitrogen addition gradient experiment in three Southern California salt marshes, we show that sediment CH4 flux increased linearly with increasing nitrogen addition (1.23 µg CH4 m-2 d-1 for each...

  20. Unified and isomer-specific NMR metabolomics database for the accurate analysis of (13)C-(1)H HSQC spectra.

    Science.gov (United States)

    Bingol, Kerem; Li, Da-Wei; Bruschweiler-Li, Lei; Cabrera, Oscar A; Megraw, Timothy; Zhang, Fengli; Brüschweiler, Rafael

    2015-02-20

    A new metabolomics database and query algorithm for the analysis of (13)C-(1)H HSQC spectra is introduced, which unifies NMR spectroscopic information on 555 metabolites from both the Biological Magnetic Resonance Data Bank (BMRB) and Human Metabolome Database (HMDB). The new database, termed Complex Mixture Analysis by NMR (COLMAR) (13)C-(1)H HSQC database, can be queried via an interactive, easy to use web interface at http://spin.ccic.ohio-state.edu/index.php/hsqc/index . Our new HSQC database separately treats slowly exchanging isomers that belong to the same metabolite, which permits improved query in cases where lowly populated isomers are below the HSQC detection limit. The performance of our new database and query web server compares favorably with the one of existing web servers, especially for spectra of samples of high complexity, including metabolite mixtures from the model organisms Drosophila melanogaster and Escherichia coli. For such samples, our web server has on average a 37% higher accuracy (true positive rate) and a 82% lower false positive rate, which makes it a useful tool for the rapid and accurate identification of metabolites from (13)C-(1)H HSQC spectra at natural abundance. This information can be combined and validated with NMR data from 2D TOCSY-type spectra that provide connectivity information not present in HSQC spectra. PMID:25333826

  1. Retention behavior of C1-C6 aliphatic monoamines on anion-exchange and polymethacrylate resins with heptylamine as eluent.

    Science.gov (United States)

    Ohta, Kazutoku; Ohashi, Masayoshi; Jin, Ji-Ye; Takeuchi, Toyohide; Fujimoto, Chuzo; Choi, Seong-Ho; Ryoo, Jae Jeong; Lee, Kwang-Pill

    2004-06-11

    Retention behavior of C1-C6, aliphatic monoamines (methylamine, ethylamine, propylamine, butylamine, amylamine and hexylamine) on columns (150 mm x 6 mm i.d.) packed with various anion-exchange resins (styrene-divinylbenzene (PS-DVB) copolymer-based strongly basic anion-exchange resin: TSKgel SAX, polymethacrylate-based strongly basic anion-exchange resin: TSKgel SuperQ-5PW and polymethacrylate-based weakly basic anion-exchange resin: TSKgel DEAE-5PW) and unfunctionized polymethacrylate resins (TSKgel G5000PW and TSKgel G3000PWXL) was investigated with basic solutions (sodium hydroxide and heptylamine) as the eluents. Due to strongly electrostatic repulsion (ion-exclusion effect) between these anion-exchange resins and these amines, peak resolution between these amines on these anion-exchange resin columns was unsatisfactory with both sodium hydroxide and heptylamine as the eluents. In contrast, these polymethacrylate resins were successfully applied as the stationary phases for the separation of these C1-C6 amines with heptylamine as eluent, because of both small hydrophobicity and small cation-exchange ability of these resins. Excellent simultaneous separation, highly sensitive conductimetric detection and symmetrical peaks for these C1-C6 amines were achieved on the TSKgel G3000PWXL column in 35 min with 5 mM heptylamine at pH 11.1 as the eluent. PMID:15250421

  2. HvPap-1 C1A protease actively participates in barley proteolysis mediated by abiotic stresses.

    Science.gov (United States)

    Velasco-Arroyo, Blanca; Diaz-Mendoza, Mercedes; Gandullo, Jacinto; Gonzalez-Melendi, Pablo; Santamaria, M Estrella; Dominguez-Figueroa, Jose D; Hensel, Goetz; Martinez, Manuel; Kumlehn, Jochen; Diaz, Isabel

    2016-07-01

    Protein breakdown and mobilization from old or stressed tissues to growing and sink organs are some of the metabolic features associated with abiotic/biotic stresses, essential for nutrient recycling. The massive degradation of proteins implies numerous proteolytic events in which cysteine-proteases are the most abundant key players. Analysing the role of barley C1A proteases in response to abiotic stresses is crucial due to their impact on plant growth and grain yield and quality. In this study, dark and nitrogen starvation treatments were selected to induce stress in barley. Results show that C1A proteases participate in the proteolytic processes triggered in leaves by both abiotic treatments, which strongly induce the expression of the HvPap-1 gene encoding a cathepsin F-like protease. Differences in biochemical parameters and C1A gene expression were found when comparing transgenic barley plants overexpressing or silencing the HvPap-1 gene and wild-type dark-treated leaves. These findings associated with morphological changes evidence a lifespan-delayed phenotype of HvPap-1 silenced lines. All these data elucidate on the role of this protease family in response to abiotic stresses and the potential of their biotechnological manipulation to control the timing of plant growth. PMID:27217548

  3. The Crystal Structure Analysis of Group B Streptococcus Sortase C1: A Model for the ;Lid; Movement upon Substrate Binding

    Energy Technology Data Exchange (ETDEWEB)

    Khare, Baldeep; Fu, Zheng-Qing; Huang, I-Hsiu; Ton-That, Hung; Narayana, Sthanam V.L. (UAB); (Georgia); (UTSMC)

    2012-02-07

    A unique feature of the class-C-type sortases, enzymes essential for Gram-positive pilus biogenesis, is the presence of a flexible 'lid' anchored in the active site. However, the mechanistic details of the 'lid' displacement, suggested to be a critical prelude for enzyme catalysis, are not yet known. This is partly due to the absence of enzyme-substrate and enzyme-inhibitor complex crystal structures. We have recently described the crystal structures of the Streptococcus agalactiae SAG2603 V/R sortase SrtC1 in two space groups (type II and type III) and that of its 'lid' mutant and proposed a role of the 'lid' as a protector of the active-site hydrophobic environment. Here, we report the crystal structures of SAG2603 V/R sortase C1 in a different space group (type I) and that of its complex with a small-molecule cysteine protease inhibitor. We observe that the catalytic Cys residue is covalently linked to the small-molecule inhibitor without lid displacement. However, the type I structure provides a view of the sortase SrtC1 lid displacement while having structural elements similar to a substrate sorting motif suitably positioned in the active site. We propose that these major conformational changes seen in the presence of a substrate mimic in the active site may represent universal features of class C sortase substrate recognition and enzyme activation.

  4. RubisCO-based CO2 fixation and C1 metabolism in the actinobacterium Pseudonocardia dioxanivorans CB1190.

    Science.gov (United States)

    Grostern, Ariel; Alvarez-Cohen, Lisa

    2013-11-01

    Pseudonocardia is an actinobacterial genus of interest due to its potential biotechnological, medical and environmental remediation applications, as well as for the ecologically relevant symbiotic relationships it forms with attine ants. Some Pseudonocardia spp. can grow autotrophically, but the genetic basis of this capability has not previously been reported. In this study, we examined autotrophy in Pseudonocardia dioxanivorans CB1190, which can grow using H2 and CO2, as well as heterotrophically. Genomic and transcriptomic analysis of CB1190 cells grown with H2/bicarbonate implicated the Calvin-Benson-Bassham (CBB) cycle in growth-supporting CO2 fixation, as well as a [NiFe] hydrogenase-encoding gene cluster in H2 oxidation. The CBB cycle genes are evolutionarily most related to actinobacterial homologues, although synteny has not been maintained. Ribulose-1,5-bisphosphate carboxylase activity was confirmed in H2/bicarbonate-grown CB1190 cells and was detected in cells grown with the C1 compounds formate, methanol and carbon monoxide. We also demonstrated the upregulation of CBB cycle genes upon exposure of CB1190 to these C1 substrates, and identified genes putatively involved in generating CO2 from the C1 substrates by using RT-qPCR. Finally, the potential for autotrophic growth of other Pseudonocardia spp. was explored, and the ecological implications of autotrophy in attine ant- and plant root-associated Pseudonocardia discussed. PMID:23663433

  5. Misdiagnosis and management of iatrogenic pseudoaneurysm of vertebral artery after Harms technique of C1-C2 fixation

    Directory of Open Access Journals (Sweden)

    MIN Li

    2012-12-01

    Full Text Available 【Abstract】 Harms technique of C1-C2 fixation for atlantoaxial complex becomes more popular due to good fusion rate and low vertebral artery injury (VAI rate. But considering the unique and variable anatomy of atlanto-axial complex, iatrogenic VAI will result in catastrophic con-sequences and provides particular surgical challenges for surgeons. To our knowledge, comparing with iatrogenic VAI in the screw hole, iatrogenic VAI in the “open space” is much rarer during the Harms technique of C1-C2 fixation. In this article, we present a case of iatrogenic vertebral artery pseudoaneurysm after Harms technique of posterior C1-C2 fixation. This case of iatrogenic VAI effectively treated by endovascular coil occlusion and external local compression was initially misdiagnosed as VAI by pedicle screw perforation. It can be concluded that intraoperative or post-operative computed angiography is very helpful to diag-nose the exact site of VAI and the combination of endovascular coil occlusion as well as external local com-pression can further prevent bleeding and abnormal verte-bral artery flow in the pseudoaneurysm. However, patients treated require further follow-up to confirm that there is no recurrence of the pseudoaneurysm. Key words: Vertebral artery; Aneurysm, false; Endovascular procedures

  6. On the possibility of determining the radial profile of hydrogen isotope composition of JET plasmas, and of deducing radial transport of the isotope ions

    International Nuclear Information System (INIS)

    Measurements of internal hydrogen isotopic composition of plasmas in JET and elsewhere have been lacking. In this report we show that it is feasible to determine the profile of relative hydrogen isotope density, using a neutral particle analyzer. Using detailed modeling of the formation of atomic flux and its measurement, we have quantified sensitivity of the deduced plasma composition to uncertainty of plasma parameters that impact on the measurement. We have tested application of the proposed methodology by experimentally determining the perturbed deuteron density profile in a hydrogen plasma, when the deuteron density at the plasma edge was modulated using a short pulse of deuterium gas. We have also determined the deuteron density diffusivity. The determinations are very crude at present; however this exercise is intended to enable us to design better experiments to determine plasma isotopic composition and the radial isotope ion diffusivities. (author)

  7. Molecular phylogeny of C1 inhibitor depicts two immunoglobulin-like domains fusion in fishes and ray-finned fishes specific intron insertion after separation from zebrafish

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Abhishek, E-mail: akumar@bot.uni-kiel.de [Department of Genetics and Molecular Biology in Botany, Institute of Botany, Christian-Albrechts-University at Kiel, Kiel (Germany); Bhandari, Anita [Molecular Physiology, Zoological Institute, Christian-Albrechts-University at Kiel, Kiel (Germany); Sarde, Sandeep J. [Department of Genetics and Molecular Biology in Botany, Institute of Botany, Christian-Albrechts-University at Kiel, Kiel (Germany); Goswami, Chandan [National Institute of Science Education and Research, Bhubaneswar, Orissa (India)

    2014-07-18

    Highlights: • C1 inhibitors of fishes have two Ig domains fused in the N-terminal end. • Spliceosomal introns gain in two Ig domains of selected ray-finned fishes. • C1 inhibitors gene is maintained from 450 MY on the same locus. • C1 inhibitors gene is missing in frog and lampreys. • C1 inhibitors of tetrapod and fishes differ in the RCL region. - Abstract: C1 inhibitor (C1IN) is a multi-facet serine protease inhibitor in the plasma cascades, inhibiting several proteases, notably, regulates both complement and contact system activation. Despite huge advancements in the understanding of C1IN based on biochemical properties and its roles in the plasma cascades, the phylogenetic history of C1IN remains uncharacterized. To date, there is no comprehensive study illustrating the phylogenetic history of C1IN. Herein, we explored phylogenetic history of C1IN gene in vertebrates. Fishes have C1IN with two immunoglobulin like domains attached in the N-terminal region. The RCL regions of CIIN from fishes and tetrapod genomes have variations at the positions P2 and P1′. Gene structures of C1IN gene from selected ray-finned fishes varied in the Ig domain region with creation of novel intron splitting exon Im2 into Im2a and Im2b. This intron is limited to ray-finned fishes with genome size reduced below 1 Gb. Hence, we suggest that genome compaction and associated double-strand break repairs are behind this intron gain. This study reveals the evolutionary history of C1IN and confirmed that this gene remains the same locus for ∼450 MY in 52 vertebrates analysed, but it is not found in frogs and lampreys.

  8. Molecular phylogeny of C1 inhibitor depicts two immunoglobulin-like domains fusion in fishes and ray-finned fishes specific intron insertion after separation from zebrafish

    International Nuclear Information System (INIS)

    Highlights: • C1 inhibitors of fishes have two Ig domains fused in the N-terminal end. • Spliceosomal introns gain in two Ig domains of selected ray-finned fishes. • C1 inhibitors gene is maintained from 450 MY on the same locus. • C1 inhibitors gene is missing in frog and lampreys. • C1 inhibitors of tetrapod and fishes differ in the RCL region. - Abstract: C1 inhibitor (C1IN) is a multi-facet serine protease inhibitor in the plasma cascades, inhibiting several proteases, notably, regulates both complement and contact system activation. Despite huge advancements in the understanding of C1IN based on biochemical properties and its roles in the plasma cascades, the phylogenetic history of C1IN remains uncharacterized. To date, there is no comprehensive study illustrating the phylogenetic history of C1IN. Herein, we explored phylogenetic history of C1IN gene in vertebrates. Fishes have C1IN with two immunoglobulin like domains attached in the N-terminal region. The RCL regions of CIIN from fishes and tetrapod genomes have variations at the positions P2 and P1′. Gene structures of C1IN gene from selected ray-finned fishes varied in the Ig domain region with creation of novel intron splitting exon Im2 into Im2a and Im2b. This intron is limited to ray-finned fishes with genome size reduced below 1 Gb. Hence, we suggest that genome compaction and associated double-strand break repairs are behind this intron gain. This study reveals the evolutionary history of C1IN and confirmed that this gene remains the same locus for ∼450 MY in 52 vertebrates analysed, but it is not found in frogs and lampreys

  9. In Vitro Toxicity of Naturally Occurring Silica Nanoparticles in C1 Coal 
in Bronchial Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Guangjian LI

    2012-10-01

    Full Text Available Background and objective China’s Xuan Wei County in Yunnan Province have the world’s highest incidence of lung cancer in nonsmoking women-20 times higher than the rest of China. Previous studies showed, this high lung cancer incidence may be associated with the silica particles embedded in the production combustion from the C1 coal. The aim of this study is to separate the silica particles from production combustion from the C1 bituminous coal in Xuan Wei County of Yunnan Province, and study in vitro toxicity of naturally occurring silica particles on BEAS-2B. Methods ①Separating the silica particles from combustion products of C1 bituminous coal by physical method, observing the morphology by Scanning Electron Microscope, analysis elements by SEM-EDX, observed the single particle morphology by Transmission Electron Microscope, analyed its particle size distribution by Laser particle size analyzer, the surface area of silica particles were determined by BET nitrogen adsorption analysis; ②Cell viability of the experimental group (silica; naturally occurring, control group (silica; industrial produced and crystalline silica was detected by assay used the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT method, and the reactive oxygen species (ROS, lactate dehydrogenase (LDH were determined after 24 h-72 h exposed to these particles. Results ①The physical method can separate silica particles from production combustion from the C1 bituminous coal, which have different size, and from 30 nm to 120 nm particles accounted for 86.8%, different morphology, irregular surface area and containing trace of aluminum, calcium and iron and other elements; ②Under the same concentration, the experiment group have higher toxicity on BEAS-2B than control groups. Conclusion ①Physical method can separate silica particles from production combustion from the C1 bituminous coal and not change the original morphology and containing trace;

  10. Avaliação de série de pacientes com artrodese C1-C2 Evaluación de diferentes casos con artrodesis C1-C2 Evaluation of different cases with C1-C2 arthrodesis

    OpenAIRE

    Cesar Salge Ghilardi; Olavo Biraghi Letaif; Alexandre Sadao Iutaka; Alexandre Fogaça Cristante; Ivan Dias Rocha; Raphael Martus Marcon; Reginaldo Perilo Oliveira; Tarcísio Eloy Pessoa de Barros Filho

    2012-01-01

    OBJETIVO: Análise retrospectiva de prontuários de pacientes com instabilidade C1-C2 de causas traumáticas e não-traumáticas, submetidos à artrodese C1-C2. MÉTODOS: Foi realizada análise retrospectiva de prontuários de 20 pacientes do ambulatório de coluna do IOT-HCFMUSP com idades entre 7 e 83 anos (média de 43 anos), de ambos os sexos. Os parâmetros radiográficos para instabilidade foram baseados na medida do intervalo atlanto-axial superior a 3 mm em adultos e a 5 mm em crianças, utilizando...

  11. The Roles of C1q/TNF-related Protein-3 (CTRP3) and C1q/TNF-related Protein-9 (CTRP9) in Obesity Related Diseases%C1q/肿瘤坏死因子相关蛋白3和9在肥胖相关疾病中的作用

    Institute of Scientific and Technical Information of China (English)

    王媛; 刘戈力

    2016-01-01

    C1q/肿瘤坏死因子相关蛋白3(CTRP3)和C1q/肿瘤坏死因子相关蛋白9(CTRP9)作为新的连接炎症和肥胖相关代谢疾病的抗炎脂肪因子之一,具有多种生物学功能。近年来针对CTRP3和CTRP9在肥胖相关疾病中的作用的研究成为热点,并发现其在肥胖相关的心血管疾病及糖脂代谢中发挥重要作用。就CTRP3和CTRP9的组织结构和功能及它们在肥胖相关疾病的发生发展中的作用进行综述。%As one of new anti-inflammatory adipokines factor with connection to inflammation and obesity related metabolic diseases, C1q/TNF-related protein-3 (CTRP3) and C1q/TNF-related protein-9 (CTRP9) have a variety of biological functions. Recently, studies of the roles in CTRP3 and CTRP9 targeted in obesity related diseases become hot, and found that they play an important role in obesity related cardiovascular disease and glucose-lipid metabolism. This article is objected to review organizational structure and function about CTRP3 and CTRP9,and its role in the development of obesity related diseases.

  12. Artrodesis C1C2 con tornillos transarticulares en artritis reumatoidea: experiencia y revisión de la literatura Artrodese C1 C2 com parafusos transarticulares em artrite reumatoide: experiência e revisão de literatura C1 C2 arthrodesis with transarticular screws in rheumatoid arthritis: experience and literature review

    Directory of Open Access Journals (Sweden)

    Lyonel Beaulieu Lalanne

    2011-01-01

    Full Text Available OBJETIVO: Describir los resultados clínicos e imagenológicos utilizando la técnica de fijación C1 C2 con tornillos transarticulares y asas de alambre en pacientes portadores de AR en un seguimiento a largo plazo y revisar la literatura actual. MÉTODO: Entre los años 2002 y 2006, 11 pacientes (9 mujeres y 2 hombres con inestabilidad C1 C2 secundaria a AR fueron intervenidos quirúrgicamente. Se realizó fijación C1 C2 con tornillos transarticulares por vía posterior más asas de alambre y aplicación de injerto óseo autólogo de cresta ilíaca. Se registró Índice de Ranawat pre y posoperatorio, Distancia Anterior Atlas Odontoides (DAAO pre y posoperatorio, tiempo operatorio, días de hospitalización, complicaciones intra y posoperatorias y tiempo de consolidación radiológica, con un seguimiento promedio de 34 meses. RESULTADOS: Todos los pacientes presentaron mejoría del Índice de Ranawat en el postoperatorio. La DAAO preoperatoria promedio fue de 11,9 mm (DS ± 2,57, rango 7 a 16, y la DAAO postoperatoria promedio fue de 3 mm (DS ± 1,20, rango 2 a 6. El tiempo quirúrgico fue de 94 minutos en promedio y el promedio de días de hospitalización fue de 7 días. No se presentaron complicaciones intraoperatorias. Un caso presentó seroma de herida operatoria que requirió tratamiento quirúrgico. El tiempo de consolidación fue en promedio 14 semanas. CONCLUSIÓN: La artrodesis atlantoaxial con tornillos y amarras es una buena alternativa para el manejo de la inestabilidad C1-C2 en pacientes portadores de AR, consiguiendo buenos resultados clínicos e imagenológicos en un seguimiento a largo plazo.OBJETIVO: Apresentar a experiência com a técnica de fixação C1-C2 com parafusos transarticulares e cerclagem de fio metálico nos pacientes portadores de AR, assim como a revisão da literatura. MÉTODO: Entre os anos 2002 e 2006, 11 pacientes (9 mulheres e 2 homens com instabilidade C1-C2 e portadores de AR foram submetidos a

  13. Role of physiological ClC-1 Cl- ion channel regulation for the excitability and function of working skeletal muscle

    DEFF Research Database (Denmark)

    Pedersen, Thomas Holm; Riisager, Anders; de Paoli, Frank Vincenzo;

    2016-01-01

    permeability for Cl- ions. Thus, in resting human muscle, ClC-1 Cl- ion channels account for ∼80% of the membrane conductance, and because active Cl- transport is limited in muscle fibers, the equilibrium potential for Cl- lies close to the resting membrane potential. These conditions—high membrane conductance...... and passive distribution—enable ClC-1 to conduct membrane current that inhibits muscle excitability. This depressing effect of ClC-1 current on muscle excitability has mostly been associated with skeletal muscle hyperexcitability in myotonia congenita, which arises from loss-of-function mutations in...... the CLCN1 gene. However, given that ClC-1 must be drastically inhibited (∼80%) before myotonia develops, more recent studies have explored whether acute and more subtle ClC-1 regulation contributes to controlling the excitability of working muscle. Methods were developed to measure ClC-1 function with...

  14. The Levels of the Lectin Pathway Serine Protease MASP-1 and Its Complex Formation with C1 Inhibitor Are Linked to the Severity of Hereditary Angioedema.

    Science.gov (United States)

    Hansen, Cecilie Bo; Csuka, Dorottya; Munthe-Fog, Lea; Varga, Lilian; Farkas, Henriette; Hansen, Karin Møller; Koch, Claus; Skjødt, Karsten; Garred, Peter; Skjoedt, Mikkel-Ole

    2015-10-15

    C1 inhibitor (C1-INH) is known to form complexes with the lectin complement pathway serine proteases MASP-1 and MASP-2. Deficiency of C1-INH is associated with hereditary angioedema (HAE), an autosomal inherited disease characterized by swelling attacks caused by elevated levels of bradykinin. MASP-1 was shown to cleave high m.w. kininogen into bradykinin; therefore, we hypothesized that MASP-1 levels and the quantity of MASP-1/C1-INH complexes might be associated with different paraclinical and clinical outcomes of HAE. We measured MASP-1 serum concentrations and endogenous MASP-1/C1-INH complex levels in 128 HAE patients and 100 controls. Relatively high levels of pre-existing MASP-1/C1-INH complexes were observed in normal serum, and we found that both the serum levels of MASP-1 and the complex formation between MASP-1 and C1-INH were significantly reduced in HAE patients compared with matched controls (p < 0.0001). The level of MASP-1 and MASP-1/C1-INH complexes in HE patients correlated with the level of C1-INH (p = 0.0009 and p = 0.0047, respectively), the level of C4 (p = 0.0084 and p < 0.0001, respectively), and the number of attacks in the year of blood sampling (p = 0.0075 and p = 0.0058, respectively). In conclusion, we show that MASP-1/C1-INH complexes circulate in normal human blood. The levels of MASP-1 and MASP-1/C1-INH complexes are reduced in HAE patients compared with controls. Both MASP-1 and MASP-1/C1-INH complexes are related to the degree of complement C4 consumption, as well as the severity of disease. These results suggest that MASP-1 may exert a previously unrecognized role in the pathophysiology of HAE. PMID:26371246

  15. Hepatitis B Virus X Protein Up-Regulates AKR1C1 Expression Through Nuclear Factor-Y in Human Hepatocarcinoma Cells

    OpenAIRE

    Kai LI; Ding, Shijia; Chen, Ke; Qin, Dongdong; Qu, Jialin; Wang, Sen; Sheng, Yanrui; Zou, Chengcheng; Chen, Limin; Tang, Hua

    2013-01-01

    Background The hepatitis B virus X (HBx) protein has long been recognized as an important transcriptional transactivator of several genes. Human aldo-keto reductase family 1, member C1 (AKR1C1), a member of the family of AKR1CS, is significantly increased in HBx-expressed cells. Objectives This study aimed to investigate the possible mechanism of HBx in regulating AKR1C1 expression in HepG2.2.15 cells and the role of AKR1C1 for HBV-induced HCC. Materials and Methods RT-PCR was performed to de...

  16. Comparison of autoantibodies to the collagen-like region of C1q in hypocomplementemic urticarial vasculitis syndrome and systemic lupus erythematosus.

    Science.gov (United States)

    Wisnieski, J J; Jones, S M

    1992-03-01

    Hypocomplementemic urticarial vasculitis syndrome (HUVS) is an apparent autoimmune disorder that resembles SLE. We previously showed that C1q precipitins in HUVS sera are IgG autoantibody to human C1q. We have compared HUVS anti-C1q autoantibody to a similar autoantibody in the serum of some patients with SLE. As with anti-C1q autoantibody in SLE sera, the HUVS autoantibody binds only to the collagen-like region (CLR) of C1q. In both HUVS and SLE, IgG2 is the predominant subclass of IgG autoantibody and IgM autoantibody to C1q is uncommon. In both diseases, anti-C1q autoantibodies bind preferentially to surface-adsorbed C1q or CLR fragments compared to these antigens in solution. Finally, when HUVS or SLE autoantibodies were added to CLR-coated wells already bound, respectively, by SLE or HUVS autoantibodies, no increases in CLR binding were observed, suggesting that HUVS and SLE autoantibodies to C1q bind to the same CLR epitope(s). PMID:1538123

  17. Deducibility of the standard model

    International Nuclear Information System (INIS)

    Full text: The standard model of High Energy Physics is derived from basic mathematical principles with no auxiliary bundles. Why do geometric images such like Solomon's Seal play a role in HEPhy? The reason for the appearance of the eightfold path is in the structure of higher dimensional Clifford algebras such as Cl(3,1). The spinors of fermions can be derived as polarized isotropic multivectors within the Clifford algebra of the Minkowski spacetime. We just assume that each spinor Clifford multiplied with its grade inverse s-hat constitutes that primitive idempotent f = ss-hat in Cl(3,1) in the minimal left ideal of which it is located, that is, we have s in fxCxCl(3,1). Then we obtain all spinors and their densities. The list of fermions is complete. The spinors presented obey the symmetries of the forces of nature. They do not rely on the addition of any auxiliary bundle. (author)

  18. Investigation of the Herzberg (C1Σ+→A1Π) band system in 12C17O

    Science.gov (United States)

    Hakalla, Rafał

    2015-10-01

    The C→A (0,1), (0,2) and (0,3) rovibronic bands of the less-abundant 12C17O isotopologue are studied in high resolution using a high-accuracy dispersive optical spectroscopy in the region of 22,800-26,100 cm-1. Calibration with respect to simultaneously recorded thorium atomic lines, obtained from several overlapped orders of the spectrum in the visible range, as well as a stainless steel hollow-cathode molecular lamp with two anodes, yields an absolute accuracy of wavenumbers measurements of about 0.0025 cm-1 for the CO spectra. All 261 spectra lines of the Herzberg band system in 12C17O, up to Jmax=34, were precisely measured and rotationally analyzed. As a result, the merged rotational constants and rotational equilibrium constants for the C1Σ+ Rydberg state, as well as the band origins, the isotope shifts, the RKR turning points, Franck-Condon factors, relative intensities, and r-centroids of the C→A system in the 12C17O isotopologue were obtained. An experimental RKR potential energy curve and vibrational levels of the C1Σ+ state in 12C17O together with highly excited k3Π, c3Π, E1Π, B1Σ+ and D‧1Σ+ states lying in the region between the first dissociation limit and the ionization potential of CO were plotted. A detailed investigation of possible perturbations that should occur in the C1Σ+(υ=0) Rydberg state of less-abundant 12C17O isotopologue in the close vicinity of the k3Π(υ=1, 2) and c3Π(υ=0) states in the region 92,000 cm-1 was performed. In the A1Π, υ=3 state of 12C17O, extensive, multi-state rotational perturbations were found and analyzed. Also, a global isotopic analysis of the C1Σ+ Rydberg state was carried out in the 12C16O, 12C17O, 13C16O, 12C18O, 13C17O, and 13C18O as well as in 14C16O and 14C18O isotopologues. This analysis enabled us to determine, amongst others, the vibrational equilibrium constants in 12C17O for the C1Σ+ state, to improve these constants in the 12C16O, 13C16O, 12C18O, 13C17O, and 13C18O isotopologues and

  19. Simultaneous analysis of C1 and C4 oxidized oligosaccharides, the products of lytic polysaccharide monooxygenases acting on cellulose.

    Science.gov (United States)

    Westereng, Bjørge; Arntzen, Magnus Ø; Aachmann, Finn L; Várnai, Anikó; Eijsink, Vincent G H; Agger, Jane Wittrup

    2016-05-01

    Lytic polysaccharide monooxygenases play a pivotal role in enzymatic deconstruction of plant cell wall material due to their ability to catalyze oxidative cleavage of glycosidic bonds. LPMOs may release different products, often in small amounts, with various oxidation patterns (C1 or C4) and with varying stabilities, making accurate analysis of product profiles a major challenge. So far, HPAEC has been the method of choice but it has limitations with respect to analysis of C4-oxidized products. Here, we compare various HPLC methods and present procedures that allow efficient separation of intact C1- and C4-oxidized products. We demonstrate that both PGC and HILIC (in WAX-mode) can separate C1- and C4-oxidized products and that PGC gives superior chromatographic performance. In contrast to HPAEC, these methods are directly compatible with mass spectroscopy and charged aerosol detection (CAD), which enables online peak validation and quantification with LOD levels in the low ng range. While the novel methods show lower resolution than HPAEC, this is compensated by easy peak identification, allowing, for example, discrimination between chromatographically highly similar native and C4-oxidized cello-oligomers. HPAEC-MS studies revealed chemical oxidation of C4-geminal diol products, which implies that peaks commonly believed to be C4-oxidized cello-oligomers, in fact are on-column generated derivatives. Non-destructive separation of C4-oxidized cello-oligosaccharides on the PGC column allowed us, for the first time, to isolate C4-oxidized standards. HPAEC fractionation of a purified C4-oxidized tetramer revealed that on-column decomposition leads to formation of the native trimer, which may explain why product mixtures generated by C4-oxidizing LPMOs seem to be rich in native oligosaccharides when analyzed by HPAEC. The findings and methods described here will aid in future studies in the emerging LPMO field. PMID:27059395

  20. COOH-terminal substitutions in the serpin C1 inhibitor that cause loop overinsertion and subsequent multimerization.

    Science.gov (United States)

    Eldering, E; Verpy, E; Roem, D; Meo, T; Tosi, M

    1995-02-10

    The region COOH-terminal to the reactive center loop is highly conserved in the serine protease inhibitor (serpin) family. We have studied the structural consequences of three substitutions (Val451-->Met, Phe455-->Ser, and Pro476-->Ser) found in this region of C1 inhibitor in patients suffering from hereditary angioedema. Equivalent substitutions have been described in alpha 1-antitrypsin and antithrombin III. The mutant C1 inhibitor proteins were only partially secreted upon transient transfection into COS-7 cells and were found to be dysfunctional. Immunoprecipitation of conditioned media demonstrated that in the intact, uncleaved form they all bind to a monoclonal antibody which recognizes specifically the protease-complexed or reactive center-cleaved normal C1 inhibitor. A second indication for an intrinsic conformational change was the increased thermostability compared to the normal protein. Furthermore, gel filtration studies showed that the Val451-->Met and Pro476-->Ser mutant proteins, and to a lesser extent Phe455-->Ser, were prone to spontaneous multimerization. Finally, a reduced susceptibility to reactive center cleavage by trypsin was observed for all three mutants, and the cleaved Val451-->Met and Pro476-->Ser mutants failed to adopt the conformation recognized by a cleavage-specific monoclonal antibody. Investigation of plasmas of patients with the Val451-->Met or Pro476-->Ser substitutions showed that these dysfunctional proteins circulate at low levels and are recognized by the complex-specific antibody. These results strongly indicate a conformational change as a result of these carboxylterminal substitutions, such that anchoring of the reactive center loop at the COOH-terminal side is not achieved properly. We propose that this results in overinsertion of the loop into beta-sheet A, which subsequently leads to multimerization. PMID:7852321

  1. A family with atypical Hailey Hailey disease--is there more to the underlying genetics than ATP2C1?

    Directory of Open Access Journals (Sweden)

    Nina van Beek

    Full Text Available The autosomal dominant Hailey Hailey disease (HHD is caused by mutations in the ATP2C1 gene encoding for human secretory pathway Ca2+/Mn2+ ATPase protein (hSPCA1 in the Golgi apparatus. Clinically, HHD presents with erosions and hyperkeratosis predominantly in the intertrigines. Here we report an exome next generation sequencing (NGS based analysis of ATPase genes in a Greek family with 3 HHD patients presenting with clinically atypical lesions mainly localized on the neck and shoulders. By NGS of one HHD-patient and in silico SNP calling and SNP filtering we identified a SNP in the expected ATP2C1 gene and SNPs in further ATPase genes. Verification in all 3 affected family members revealed a heterozygous frameshift deletion at position 2355_2358 in exon 24 of ATP2C1 in all three patients. 7 additional SNPs in 4 ATPase genes (ATP9B, ATP11A, ATP2B3 and ATP13A5 were identified. The SNPs rs138177421 in the ATP9B gene and rs2280268 in the ATP13A5 gene were detected in all 3 affected, but not in 2 non affected family members. The SNPs in the ATP2B3 and ATP11A gene as well as further SNPs in the ATP13A5 gene could not be confirmed in all affected family members. One may speculate that besides the level of functional hSPCA1 protein, levels of other ATPase proteins may influence expressivity of the disease and might also contribute, as in this case, to atypical presentations.

  2. A Family with Atypical Hailey Hailey Disease- Is There More to the Underlying Genetics than ATP2C1?

    Science.gov (United States)

    Gupta, Yask; Möller, Steffen; Freitag, Miriam; Lemcke, Susanne; Recke, Andreas; Zillikens, Detlef; Schmidt, Enno; Ibrahim, Saleh

    2015-01-01

    The autosomal dominant Hailey Hailey disease (HHD) is caused by mutations in the ATP2C1 gene encoding for human secretory pathway Ca2+/Mn2+ ATPase protein (hSPCA1) in the Golgi apparatus. Clinically, HHD presents with erosions and hyperkeratosis predominantly in the intertrigines. Here we report an exome next generation sequencing (NGS) based analysis of ATPase genes in a Greek family with 3 HHD patients presenting with clinically atypical lesions mainly localized on the neck and shoulders. By NGS of one HHD-patient and in silico SNP calling and SNP filtering we identified a SNP in the expected ATP2C1 gene and SNPs in further ATPase genes. Verification in all 3 affected family members revealed a heterozygous frameshift deletion at position 2355_2358 in exon 24 of ATP2C1 in all three patients. 7 additional SNPs in 4 ATPase genes (ATP9B, ATP11A, ATP2B3 and ATP13A5) were identified. The SNPs rs138177421 in the ATP9B gene and rs2280268 in the ATP13A5 gene were detected in all 3 affected, but not in 2 non affected family members. The SNPs in the ATP2B3 and ATP11A gene as well as further SNPs in the ATP13A5 gene could not be confirmed in all affected family members. One may speculate that besides the level of functional hSPCA1 protein, levels of other ATPase proteins may influence expressivity of the disease and might also contribute, as in this case, to atypical presentations. PMID:25837627

  3. A family with atypical Hailey Hailey disease--is there more to the underlying genetics than ATP2C1?

    Science.gov (United States)

    van Beek, Nina; Patsatsi, Aikaterini; Gupta, Yask; Möller, Steffen; Freitag, Miriam; Lemcke, Susanne; Recke, Andreas; Zillikens, Detlef; Schmidt, Enno; Ibrahim, Saleh

    2015-01-01

    The autosomal dominant Hailey Hailey disease (HHD) is caused by mutations in the ATP2C1 gene encoding for human secretory pathway Ca2+/Mn2+ ATPase protein (hSPCA1) in the Golgi apparatus. Clinically, HHD presents with erosions and hyperkeratosis predominantly in the intertrigines. Here we report an exome next generation sequencing (NGS) based analysis of ATPase genes in a Greek family with 3 HHD patients presenting with clinically atypical lesions mainly localized on the neck and shoulders. By NGS of one HHD-patient and in silico SNP calling and SNP filtering we identified a SNP in the expected ATP2C1 gene and SNPs in further ATPase genes. Verification in all 3 affected family members revealed a heterozygous frameshift deletion at position 2355_2358 in exon 24 of ATP2C1 in all three patients. 7 additional SNPs in 4 ATPase genes (ATP9B, ATP11A, ATP2B3 and ATP13A5) were identified. The SNPs rs138177421 in the ATP9B gene and rs2280268 in the ATP13A5 gene were detected in all 3 affected, but not in 2 non affected family members. The SNPs in the ATP2B3 and ATP11A gene as well as further SNPs in the ATP13A5 gene could not be confirmed in all affected family members. One may speculate that besides the level of functional hSPCA1 protein, levels of other ATPase proteins may influence expressivity of the disease and might also contribute, as in this case, to atypical presentations. PMID:25837627

  4. Structural And Biochemical Studies of Botulinum Neurotoxin Serotype C1 Light Chain Protease: Implications for Dual Substrate Specificity

    Energy Technology Data Exchange (ETDEWEB)

    Jin, R.; Sikorra, S.; Stegmann, C.M.; Pich, A.; Binz, T.; Brunger, A.T.

    2009-06-01

    Clostridial neurotoxins are the causative agents of the neuroparalytic disease botulism and tetanus. They block neurotransmitter release through specific proteolysis of one of the three soluble N-ethylmaleimide-sensitive-factor attachment protein receptors (SNAREs) SNAP-25, syntaxin, and synaptobrevin, which constitute part of the synaptic vesicle fusion machinery. The catalytic component of the clostridial neurotoxins is their light chain (LC), a Zn2+ endopeptidase. There are seven structurally and functionally related botulinum neurotoxins (BoNTs), termed serotype A to G, and tetanus neurotoxin (TeNT). Each of them exhibits unique specificity for their target SNAREs and peptide bond(s) they cleave. The mechanisms of action for substrate recognition and target cleavage are largely unknown. Here, we report structural and biochemical studies of BoNT/C1-LC, which is unique among BoNTs in that it exhibits dual specificity toward both syntaxin and SNAP-25. A distinct pocket (S1') near the active site likely achieves the correct register for the cleavage site by only allowing Ala as the P1' residue for both SNAP-25 and syntaxin. Mutations of this SNAP-25 residue dramatically reduce enzymatic activity. The remote a-exosite that was previously identified in the complex of BoNT/A-LC and SNAP-25 is structurally conserved in BoNT/C1. However, mutagenesis experiments show that the a-exosite of BoNT/C1 plays a less stringent role in substrate discrimination in comparison to that of BoNT/A, which could account for its dual substrate specificity.

  5. Protective effect of Porphyra yezoensis glycoprotein on D-galactosamine‑induced cytotoxicity in Hepa 1c1c7 cells.

    Science.gov (United States)

    Choi, Jeong-Wook; Kim, Young-Min; Park, Su-Jin; Kim, In-Hye; Nam, Taek-Jeong

    2015-05-01

    The present study aimed to examine the signaling pathways and enzyme activity associated with the protective effect of Porphyra yezoensis glycoprotein (PYGP) on D‑galactosamine (D‑GaIN)‑induced cytotoxicity in Hepa 1c1c7 cells. D‑GaIN is commonly used to induce hepatic injury models in vivo as well as in vitro. PYGP was extracted from Porphyra yezoensis, a red algae distributed along the coasts of Republic of Korea, China and Japan. In the present study, Hepa 1c1c7 cells were pre‑treated with PYGP (20 and 40 µg/ml) for 24 h and then the media was replaced with D‑GaIN (20 mM) and PYGP (20 and 40 µg/ml). The results demonstrated that D‑GaIN induced Hepa 1c1c7 cell death and pretreatment with PYGP was found to attenuate D‑GaIN toxicity. In addition, D‑GaIN decreased the antioxidant activity and increased lipid peroxidation processes; however, pre‑treatment with PYGP reduced the generation of lipid peroxidation products, such as thiobarbituric acid reactive substances, as well as increased the activity of antioxidant enzymes, including superoxide dismutase, catalase and glutathione‑s‑transferase (GST). PYGP was shown to suppress the overexpression of extracellular signal‑regulated kinase, c‑jun N‑terminal kinase and p38 mitogen‑activated protein kinase (MAPK) phosphorylation induced by D‑GaIN. Furthermore, PYGP increased the protein expression of nuclear factor erythroid 2‑related factor 2 (Nrf2), quinine oxidoreductase 1, GST and heme oxygenase 1 protein expression. These results suggested that PYGP had cytoprotective effects against D‑GaIN‑induced cell damage, which may be associated with MAPKs and the Nrf2 signaling pathway. PMID:25626067

  6. New insight into the spatiotemporal variability and source apportionments of C1-C4 alkyl nitrates in Hong Kong

    Science.gov (United States)

    Ling, Z. H.; Guo, H.; Simpson, I. J.; Saunders, S. M.; Lam, S. H. M.; Lyu, X. P.; Blake, D. R.

    2015-08-01

    Alkyl nitrates (RONO2) were measured concurrently at a mountain site (TMS) and an urban site (TW) at the foot of the same mountain in Hong Kong from September to November 2010, when high O3 mixing ratios were frequently observed. The abundance and temporal patterns of five C1-C4 RONO2 and their parent hydrocarbons (RH), the RONO2/RH ratios and photochemical age of air masses at TMS differed from those at TW, reflecting different contributions of direct emissions and secondary formation of RONO2 at the two sites. Relative to 2-BuONO2/n-butane, the measured ratios of C1-C2 RONO2/RH at the two sites exhibited significant positive deviations from pure photochemical (PP) curves and background initial ratio (BIR) curves obtained from laboratory kinetic data, suggesting that background mixing ratios had a significant influence on the RONO2 and RH distributions. In contrast to the C1-C2 RONO2/RH ratios, the evolution for the measured ratios of C3 RONO2/RH to 2-BuONO2/n-butane agreed well with the ratio distributions in the PP and BIR curves at the two sites. Furthermore, the ratios of 1-/2-PrONO2 and yields of 1- and 2-PrONO2 suggested that the C3 RONO2 were mainly from secondary formation at TMS, whereas secondary formation and other additional sources had a significant influence on C3 RONO2 mixing ratios at TW. The source apportionment results confirmed that secondary formation was the dominant contributor to all the RONO2 at TMS, while most of the RONO2 at TW were from secondary formation and biomass burning. The findings of the source apportionments and photochemical evolution of RONO2 are helpful to evaluate photochemical processing in Hong Kong using RONO2 as an indicator.

  7. Electron-Vibrational Coupling and Fluorescence Spectra of Tetra-, Penta-, and Hexacoordinated Chlorophylls c1 and c2.

    Science.gov (United States)

    Etinski, Mihajlo; Petković, Milena; Ristić, Miroslav M; Marian, Christel M

    2015-08-13

    Chlorophylls (Chls) are a group of pigments related to light absorption, excitation energy, and electron transfer in photosynthetic complexes. Given the importance of intramolecular nuclear motion for these electronic processes, many experimental studies were performed in order to relate its coupling to electronic coordinates of these pigments, but a detailed analysis is still lacking for isolated Chls c1 and c2. To gain insight into the intramolecular motion and fluoroscence spectra of these two pigments in tetra-, penta-, and hexacoodinated states, we performed a quantum chemical study based on density functional theory and multimode harmonic approximation with displaced, distorted, and rotated normal modes. In order to benchmark the employed methods, we simulated the high-resolution fluorescence spectra of tetracoodinated Chls a, b, and d and compared them with available experimental spectra obtained with fluorescence line-narrowing techniques. Although the experimental spectra were obtained for ligand coordinated Chls, qualitatively good agreement was found between the simulated and experimental spectra. Almost all resonances were reproduced in the spectroscopically interesting region from 200 to 1700 cm(-1). The significance of mode distortion and rotation for the simulated spectra is discussed. The fluorescence spectra of Chls c1 and c2 consist of a group of peaks in the 200-450 cm(-1) spectral range, a group of weak peaks from 700 to 1000 cm(-1), and a large group of strong peaks from 1100 to 1600 cm(-1). Ligand effects are also addressed, and a mode is identified as a sensitive probe for the coordination state of Chls c1 and c2. PMID:26189597

  8. Functional Divergence of the Nuclear Receptor NR2C1 as a Modulator of Pluripotentiality During Hominid Evolution.

    Science.gov (United States)

    Baker, Jennifer L; Dunn, Katherine A; Mingrone, Joseph; Wood, Bernard A; Karpinski, Beverly A; Sherwood, Chet C; Wildman, Derek E; Maynard, Thomas M; Bielawski, Joseph P

    2016-06-01

    Genes encoding nuclear receptors (NRs) are attractive as candidates for investigating the evolution of gene regulation because they (1) have a direct effect on gene expression and (2) modulate many cellular processes that underlie development. We employed a three-phase investigation linking NR molecular evolution among primates with direct experimental assessment of NR function. Phase 1 was an analysis of NR domain evolution and the results were used to guide the design of phase 2, a codon-model-based survey for alterations of natural selection within the hominids. By using a series of reliability and robustness analyses we selected a single gene, NR2C1, as the best candidate for experimental assessment. We carried out assays to determine whether changes between the ancestral and extant NR2C1s could have impacted stem cell pluripotency (phase 3). We evaluated human, chimpanzee, and ancestral NR2C1 for transcriptional modulation of Oct4 and Nanog (key regulators of pluripotency and cell lineage commitment), promoter activity for Pepck (a proxy for differentiation in numerous cell types), and average size of embryological stem cell colonies (a proxy for the self-renewal capacity of pluripotent cells). Results supported the signal for alteration of natural selection identified in phase 2. We suggest that adaptive evolution of gene regulation has impacted several aspects of pluripotentiality within primates. Our study illustrates that the combination of targeted evolutionary surveys and experimental analysis is an effective strategy for investigating the evolution of gene regulation with respect to developmental phenotypes. PMID:27075724

  9. Mammalian proapoptotic factor ChaC1 and its homologues function as γ-glutamyl cyclotransferases acting specifically on glutathione.

    Science.gov (United States)

    Kumar, Akhilesh; Tikoo, Shweta; Maity, Shuvadeep; Sengupta, Shantanu; Sengupta, Sagar; Kaur, Amandeep; Bachhawat, Anand Kumar

    2012-12-01

    ChaC1 is a mammalian proapoptic protein of unknown function induced during endoplasmic reticulum stress. We show using in vivo studies and novel in vitro assays that the ChaC family of proteins function as γ-glutamyl cyclotransferases acting specifically to degrade glutathione but not other γ-glutamyl peptides. The overexpression of these proteins (but not the catalytically dead E>Q mutants) led to glutathione depletion and enhanced apoptosis in yeast. The ChaC family is conversed across all phyla and represents a new pathway for glutathione degradation in living cells, and the first cytosolic pathway for glutathione degradation in mammalian cells. PMID:23070364

  10. Congenital defects of C1 arches and odontoid process in a child with Down′s syndrome: A case presentation

    Directory of Open Access Journals (Sweden)

    Catherine Hatzantonis

    2016-01-01

    Full Text Available We present the case of a 2-year-old child with Down′s syndrome who presented to our unit with torticollis. Imaging studies revealed the rare occurrence of anterior and posterior C1 arch defects, absent odontoid process, and atlantoaxial subluxation. We managed her conservatively for 3 years without neurological deficits or worsening of atlantoaxial subluxation. We discuss the rare occurrences of anterior and posterior arch defects of the atlas, the radiological presentations of axis defects in patients, and the occurrence of atlantoaxial instability in patients with Down′s syndrome. Management options with consideration to surgery in asymptomatic and symptomatic patients are also discussed.

  11. Congenital defects of C1 arches and odontoid process in a child with Down's syndrome: A case presentation.

    Science.gov (United States)

    Hatzantonis, Catherine; Muquit, Samiul; Nasto, Luigi Aurelio; Mehdian, Hossein

    2016-01-01

    We present the case of a 2-year-old child with Down's syndrome who presented to our unit with torticollis. Imaging studies revealed the rare occurrence of anterior and posterior C1 arch defects, absent odontoid process, and atlantoaxial subluxation. We managed her conservatively for 3 years without neurological deficits or worsening of atlantoaxial subluxation. We discuss the rare occurrences of anterior and posterior arch defects of the atlas, the radiological presentations of axis defects in patients, and the occurrence of atlantoaxial instability in patients with Down's syndrome. Management options with consideration to surgery in asymptomatic and symptomatic patients are also discussed. PMID:27217660

  12. Effect of psychosocial stress on FKBP5 and NR3C1 gene expression in healthy young men

    OpenAIRE

    Nina Höhne; Hildegard Pfister; Tanja Brückl; Petra Zimmermann; Manfred Uhr; Florian Holsboer; Marcus Ising

    2012-01-01

    Stress diseases such as affective disorders are often characterized by a disturbed regulation of the hypothalamus-pituitary-adrenocortical (HPA) axis. This dysregulation can be explained by an impaired function of the receptors involved in the HPA-axis regulation, for example, the glucocorticoid receptors (GR). The regulation process of the HPA axis and the GR function are influenced by several genes, for instance by NR3C1 coding for the GR and also by FKBP5, a co-chaperone in the GR-complex....

  13. A Time-Dependent Classical Solution of C=1 String Field Theory and Non-Perturbative Effects

    CERN Document Server

    Dhar, A; Wadia, S R; Dhar, Avinash; Mandal, Gautam; Wadia, Spenta R.

    1993-01-01

    We describe a real-time classical solution of $c=1$ string field theory written in terms of the phase space density, $u(p,q,t)$, of the equivalent fermion theory. The solution corresponds to tunnelling of a single fermion above the filled fermi sea and leads to amplitudes that go as $\\exp(- C/ \\gst)$. We discuss how one can use this technique to describe non-perturbative effects in the Marinari-Parisi model. We also discuss implications of this type of solution for the two-dimensional black hole.

  14. Mechanisms involved in PGE2-induced transactivation of the epidermal growth factor receptor in MH1C1 hepatocarcinoma cells

    Directory of Open Access Journals (Sweden)

    Tveteraas Ingun

    2012-09-01

    Full Text Available Abstract Background It is important to understand the mechanisms by which the cells integrate signals from different receptors. Several lines of evidence implicate epidermal growth factor (EGF receptor (EGFR in the pathophysiology of hepatocarcinomas. Data also suggest a role of prostaglandins in some of these tumours, through their receptors of the G protein-coupled receptor (GPCR family. In this study we have investigated mechanisms of interaction between signalling from prostaglandin receptors and EGFR in hepatocarcinoma cells. Methods The rat hepatocarcinoma cell line MH1C1 and normal rat hepatocytes in primary culture were stimulated with EGF or prostaglandin E2 (PGE2 and in some experiments also PGF2α. DNA synthesis was determined by incorporation of radiolabelled thymidine into DNA, phosphorylation of proteins in signalling pathways was assessed by Western blotting, mRNA expression of prostaglandin receptors was determined using qRT-PCR, accumulation of inositol phosphates was measured by incorporation of radiolabelled inositol, and cAMP was determined by radioimmunoassay. Results In the MH1C1 hepatocarcinoma cells, stimulation with PGE2 or PGF2α caused phosphorylation of the EGFR, Akt, and ERK, which could be blocked by the EGFR tyrosine kinase inhibitor gefitinib. This did not occur in primary hepatocytes. qRT-PCR revealed expression of EP1, EP4, and FP receptor mRNA in MH1C1 cells. PGE2 stimulated accumulation of inositol phosphates but not cAMP in these cells, suggesting signalling via PLCβ. While pretreatment with EP1 and EP4 receptor antagonists did not inhibit the effect of PGE2, pretreatment with an FP receptor antagonist blocked the phosphorylation of EGFR, Akt and ERK. Further studies suggested that the PGE2-induced signal was mediated via Ca2+ release and not PKC activation, and that it proceeded through Src and shedding of membrane-bound EGFR ligand precursors by proteinases of the ADAM family. Conclusion The results

  15. High prevalence of hepatitis B virus genotype C/C1 in the Minangkabau ethnic group in Indonesia

    Directory of Open Access Journals (Sweden)

    Siburian Marlinang D

    2013-01-01

    Full Text Available Abstract Background The Minangkabau is one of the major ethnic groups in Indonesia. Previous studies with a limited number of samples have shown a different prevalence of HBV/C in the Minangkabau compared to the Indonesian population in general. The aim of this study was to assess the HBV genotype distribution pattern and the prevalence of pre-S, T1753V and A1762T/G1764A mutations among the Minangkabau HBV carriers. The samples were collected from Padang, West Sumatera and from western Java. Mixed primers for specific genotypes were used to determine the HBV genotype. Pre-S or S genes were amplified, sequenced and aligned with reference sequences from GenBank to derive a phylogenetic tree for subgenotyping. Pre-S genes were also analyzed for mutations. The basal core promoter (BCP region was amplified and directly sequenced to analyze T1753V and A1762T/G1764A mutations. Results The predominant HBV genotype among the Minangkabau HBV carriers (n=117 was C (72.6% followed by B (24.8% and co-infection with B and C (2.6%. The prevalence of pre-S mutations, including both the pre-S deletion and pre-S2 start codon mutation, was 41.0%, and the T1753V and A1762T/G1764A mutations were found in 51.9% and 71.2% respectively. HBV/C1 was the predominant HBV subgenotype in the Minangkabau HBV carriers, and was found in 66.2%, followed by B3, B7, C8, B2, B9, C2, and C10 (18.3%, 7.0%, 2.8%, 1.4%, 1.4%, 1.4%, and 1.4% respectively. From samples that were found to be co-infected with HBV B and C, two samples were successfully cloned and subgenotyped, including one with mixed subgenotypes of B3 and C1, and another one with mixed subgenotypes of B7, C1, putative intergenotypic of B/A, and C/A. Furthermore, three samples from donors of non-Minangkabau ethnicity from Padang were found to be infected with an intragenotypic recombination form, including a putative recombinant of B8/B3 and B9/B7. Conclusion HBV/C with subgenotype C1 was the predominant HBV genotype among

  16. Effects of Rutaecarpine on Hydrogen Peroxide-Induced Apoptosis in Murine Hepa-1c1c7 Cells

    OpenAIRE

    Lee, Sung-Jin; Ahn, Hyunjin; Nam, Kung-Woo; Kim, Kyeong Ho; Mar, Woongchon

    2012-01-01

    The aim of this study was to investigate the inhibitory effects of rutaecarpine on DNA strand breaks and apoptosis induced by hydrogen peroxide (H2O2) in murine Hepa-1c1c7 cells. Oxidative DNA damage was estimated by nuclear condensation assessment, fluorescence-activated cell sorting analysis, and Comet assay. Rutaecarpine inhibited cell death induced by 500 μM H2O2, as assessed by 4',6-diamidino-2-phenylindole (DAPI) staining. Treatment with rutaecarpine reduced the number of DNA strand bre...

  17. Fibulin-1C, C1 Esterase Inhibitor and Glucose Regulated Protein 75 Interact with the CREC Proteins, Calumenin and Reticulocalbin

    DEFF Research Database (Denmark)

    Hansen, G. A. W.; Ludvigsen, M.; Jacobsen, C.;

    2015-01-01

    Affinity purification, immunoprecipitation, gel electrophoresis and mass spectrometry were used to identify fibulin-1C, C1 esterase inhibitor and glucose regulated protein 75, grp75, as binding partners of the CREC proteins, calumenin and reticulocalbin. Surface plasmon resonance was used to verify...... interacted with both proteins with an estimated dissociation constant at 1 mu M for reticulocalbin and 150 nM for calumenin. The interaction, at least for calumenin, was dependent upon the presence of Ca2+ with strong interaction at 3.5 mM while no detectable interaction could be found at 0.1 mM. Grp75 binds...

  18. Characterization of a purified thermostable xylanase from Caldicoprobacter algeriensis sp. nov. strain TH7C1(T)

    OpenAIRE

    Bouanane-Darenfed, A.; Boucherba, N.; Bouacem, K.; Gagaoua, M.; Joseph, M; Kebbouche-Gana, S.; Nateche, F.; Hacene, H.; Ollivier, Bernard; Cayol, J. L.; Fardeau, Marie-Laure

    2016-01-01

    The present study investigates the purification and biochemical characterization of an extracellular thermostable xylanase (called XYN35) from Caldicoprobacter algeriensis sp. nov., strain TH7C1(T), a thermophilic, anaerobic strain isolated from the hydrothermal hot spring of Guelma (Algeria). The maximum xylanase activity recorded after 24 h of incubation at 70 degrees C and in an optimized medium containing 10 g/L mix birchwood-and oats spelt-xylan was 250 U/mL. The pure protein was obtaine...

  19. Some Properties of the M3D-C1 Form of the 3D Magnetohydrodynamics Equations

    International Nuclear Information System (INIS)

    We introduce a set of scalar variables and projection operators for the vector momentum and magnetic field evolution equations that have several unique and desirable properties, making them a preferred system for solving the magnetohydrodynamics equations in a torus with a strong toroidal magnetic field. We derive a 'weak form' of these equations that explicitly conserves energy and is suitable for a Galerkin finite element formulation provided the basis elements have C1 continuity. Systems of reduced equations are discussed, along with their energy conservation properties. An implicit time advance is presented that adds diagonally dominant self-adjoint energy terms to the mass matrix to obtain numerical stability.

  20. The Effect of Nitrogen Enrichment on C1-Cycling Microorganisms and Methane Flux in Salt Marsh Sediments

    OpenAIRE

    Irvine, Irina C.; Vivanco, Lucía; Peris N. Bentley; Martiny, Jennifer B. H.

    2012-01-01

    Methane (CH4) flux from ecosystems is driven by C1-cycling microorganisms – the methanogens and the methylotrophs. Little is understood about what regulates these communities, complicating predictions about how global change drivers such as nitrogen enrichment will affect methane cycling. Using a nitrogen addition gradient experiment in three Southern California salt marshes, we show that sediment CH4 flux increased linearly with increasing nitrogen addition (1.23 μg CH4 m−2 day−1 for each g ...

  1. The four hexamerin genes in the honey bee: structure, molecular evolution and function deduced from expression patterns in queens, workers and drones

    Directory of Open Access Journals (Sweden)

    Martins Juliana R

    2010-03-01

    Full Text Available Abstract Background Hexamerins are hemocyanin-derived proteins that have lost the ability to bind copper ions and transport oxygen; instead, they became storage proteins. The current study aimed to broaden our knowledge on the hexamerin genes found in the honey bee genome by exploring their structural characteristics, expression profiles, evolution, and functions in the life cycle of workers, drones and queens. Results The hexamerin genes of the honey bee (hex 70a, hex 70b, hex 70c and hex 110 diverge considerably in structure, so that the overall amino acid identity shared among their deduced protein subunits varies from 30 to 42%. Bioinformatics search for motifs in the respective upstream control regions (UCRs revealed six overrepresented motifs including a potential binding site for Ultraspiracle (Usp, a target of juvenile hormone (JH. The expression of these genes was induced by topical application of JH on worker larvae. The four genes are highly transcribed by the larval fat body, although with significant differences in transcript levels, but only hex 110 and hex 70a are re-induced in the adult fat body in a caste- and sex-specific fashion, workers showing the highest expression. Transcripts for hex 110, hex 70a and hex70b were detected in developing ovaries and testes, and hex 110 was highly transcribed in the ovaries of egg-laying queens. A phylogenetic analysis revealed that HEX 110 is located at the most basal position among the holometabola hexamerins, and like HEX 70a and HEX 70c, it shares potential orthology relationship with hexamerins from other hymenopteran species. Conclusions Striking differences were found in the structure and developmental expression of the four hexamerin genes in the honey bee. The presence of a potential binding site for Usp in the respective 5' UCRs, and the results of experiments on JH level manipulation in vivo support the hypothesis of regulation by JH. Transcript levels and patterns in the fat body

  2. Role of Inositol Phosphosphingolipid Phospholipase C1, the Yeast Homolog of Neutral Sphingomyelinases in DNA Damage Response and Diseases

    Directory of Open Access Journals (Sweden)

    Kaushlendra Tripathi

    2015-01-01

    Full Text Available Sphingolipids play a very crucial role in many diseases and are well-known as signaling mediators in many pathways. Sphingolipids are produced during the de novo process in the ER (endoplasmic reticulum from the nonsphingolipid precursor and comprise both structural and bioactive lipids. Ceramide is the central core of the sphingolipid pathway, and its production has been observed following various treatments that can induce several different cellular effects including growth arrest, DNA damage, apoptosis, differentiation, and senescence. Ceramides are generally produced through the sphingomyelin hydrolysis and catalyzed by the enzyme sphingomyelinase (SMase in mammals. Presently, there are many known SMases and they are categorized into three groups acid SMases (aSMases, alkaline SMases (alk-SMASES, and neutral SMases (nSMases. The yeast homolog of mammalians neutral SMases is inositol phosphosphingolipid phospholipase C. Yeasts generally have inositol phosphosphingolipids instead of sphingomyelin, which may act as a homolog of mammalian sphingomyelin. In this review, we shall explain the structure and function of inositol phosphosphingolipid phospholipase C1, its localization inside the cells, mechanisms, and its roles in various cell responses during replication stresses and diseases. This review will also give a new basis for our understanding for the mechanisms and nature of the inositol phosphosphingolipid phospholipase C1/nSMase.

  3. The role of the glucocorticoid receptor gene (NR3C1) for the processing of aversive stimuli.

    Science.gov (United States)

    Schneider, Katja Kerstin; Frings, Christian; Meyer, Jobst; Schote, Andrea B

    2016-06-01

    The glucocorticoid receptor (GR) is a crucial component of the hypothalamus-pituitary-adrenal (HPA) axis and as such a part of the stress response system. An impairment of the GR not only alters the level of glucocorticoids, but also modulates cognitive functions and the processing of emotional stimuli. We tested the effects of functional polymorphisms of the GR-encoding gene (NR3C1) on the processing of emotional stimuli on a basal level. In a sample of n=182 participants, we found a haplotype (NR3C1-CTGGACA) to modulate the performance in an emotional reaction time task. Compared to non-carriers, participants who carried the haplotype were quicker to react after aversive stimuli had been presented. In contrast, the presence of the haplotype had no effect on the processing of neutral stimuli. We conclude that properties of the glucocorticoid receptor contribute to the processing of emotional stimuli and influence the intensity of their processing even in the absence of acute stressors. PMID:26689331

  4. Integral experiments on in-vessel coolability and vessel creep: results and analysis of the FOREVER-C1 test

    International Nuclear Information System (INIS)

    This paper describes the FOREVER (Failure Of REactor VEssel Retention) experimental program, which is currently underway at the Division of Nuclear Power Safety, Royal Institute of Technology (RIT/NPS). The objectives of the FOREVER experiments are to obtain data and develop validated models (i) on the melt coolability process inside the vessel, in the presence of water (in particular, on the efficacy of the postulated gap cooling to preclude vessel failure); and (ii) on the lower head failure due to the creep process in the absence of water inside and/or outside the lower head. The paper presents the experimental results and analysis of the first FOREVER-C1 test. During this experiment, the 1/10th scale pressure vessel, heated to about 900degC and pressurized to 26 bars, was subjected to creep deformation in a non-stop 24-hours test. The vessel wall displacement data clearly shows different stages of the vessel deformation due to thermal expansion, elastic, plastic and creep processes. The maximum displacement was observed at the lowermost region of the vessel lower plenum. Information on the FOREVER-C1 measured thermal characteristics and analysis of the observed thermal and structural behavior is presented. The coupled nature of thermal and mechanical processes, as well as the effect of other system conditions (such as depressurization) on the melt pool and vessel temperature responses are analyzed. (author)

  5. Identification of human hnRNP C1/C2 as a dengue virus NS1-interacting protein

    International Nuclear Information System (INIS)

    Dengue virus nonstructural protein 1 (NS1) is a key glycoprotein involved in the production of infectious virus and the pathogenesis of dengue diseases. Very little is known how NS1 interacts with host cellular proteins and functions in dengue virus-infected cells. This study aimed at identifying NS1-interacting host cellular proteins in dengue virus-infected cells by employing co-immunoprecipitation, two-dimensional gel electrophoresis, and mass spectrometry. Using lysates of dengue virus-infected human embryonic kidney cells (HEK 293T), immunoprecipitation with an anti-NS1 monoclonal antibody revealed eight isoforms of dengue virus NS1 and a 40-kDa protein, which was subsequently identified by quadrupole time-of-flight tandem mass spectrometry (Q-TOF MS/MS) as human heterogeneous nuclear ribonucleoprotein (hnRNP) C1/C2. Further investigation by co-immunoprecipitation and co-localization confirmed the association of hnRNP C1/C2 and dengue virus NS1 proteins in dengue virus-infected cells. Their interaction may have implications in virus replication and/or cellular responses favorable to survival of the virus in host cells

  6. Suppression of CYP1A1 expression by naringenin in murine Hepa-1c1c7 cells.

    Science.gov (United States)

    Kim, Ji Young; Han, Eun Hee; Shin, Dong Weon; Jeong, Tae Cheon; Lee, Eung Seok; Woo, Eun-Rhan; Jeong, Hye Gwang

    2004-08-01

    Naringenin, dietary flavonoid, is antioxidant constituents of many citrus fruits. In the present study, we investigated the effect of naringenin on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible CYP1A1 gene expression in mouse hepatoma Hepa-1c1c7 cells. Naringenin alone did not affect CYP1A1-specific 7-ethoxyresorufin O-deethylase (EROD) activity. In contrast, the TCDD-inducible EROD activities were markedly reduced upon concomitant treatment with TCDD and naringenin in a dose dependent manner. TCDD-induced CYP1A1 mRNA level was also markedly suppressed by naringenin. A transient transfection assay using dioxin-response element (DRE)-linked luciferase and electrophoretic mobility shift assay revealed that naringenin reduced transformation of the aryl hydrocarbons receptor(AhR) to a form capable of specifically binding to the DRE sequence in the promoter of the CYP1A1 gene. These results suggest the down regulation of the CYP1A1 gene expression by either naringenin in Hepa-1c1c7 cells might be antagonism of the DRE binding potential of nuclear AhR. PMID:15460448

  7. Suppression of CYP1A1 expression by 4-nonylphenol in murine Hepa-1c1c7 cells.

    Science.gov (United States)

    Jeong, H G; Kim, J Y; Choi, C Y; You, H J; Hahm, K

    2001-04-10

    This study investigated the effects that 4-nonylphenol (NP) has on CYP1A1 expression in Hepa-1c1c7 cell cultures. NP alone did not affect CYP1A1-specific 7-ethoxyresorufin-O-deethylase (EROD) activity. In contrast, the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible EROD activities were markedly reduced upon concomitant treatment with TCDD and NP in a dose-dependent manner. Treatment with tamoxifen, an anti-estrogen that acts through the estrogen receptor, did not affect the suppressive effects that NP has on TCDD-inducible EROD activity. The TCDD-inducible CYP1A1 mRNA levels were markedly suppressed upon concomitant treatment with TCDD and NP that is consistent with their effects on EROD activity. A transient transfection assay using dioxin-response element (DRE)-linked luciferase and an electrophoretic mobility shift assay revealed that NP reduced the transformation of the aryl hydrocarbon (Ah) receptor to a form capable of binding specifically to the DRE sequence of the CYP1A1 gene promoter. These results suggest that the down-regulation of CYP1A1 gene expression by NP in Hepa-1c1c7 cells might be an antagonism of the DRE-binding potential of the nuclear Ah receptor, but is not mediated through the estradiol receptor. PMID:11248424

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

    DEFF Research Database (Denmark)

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

    1996-01-01

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

  9. Identification of polymorphisms in the human glucocorticoid receptor gene (NR3C1) in a multi-racial asthma case and control screening panel

    NARCIS (Netherlands)

    Hawkins, GA; Amelung, PJ; Smith, RS; Jongepier, H; Howard, TD; Koppelman, GH; Meyers, DA; Bleecker, ER; Postma, DS

    2004-01-01

    The glucocorticoid receptor (GR) gene (NR3C1) maps to 5q31, a region genetically linked to asthma. In this study, NR3C1 exons 1A, 1B, and exons 1C to 9 (alpha and beta) were sequenced in a screening panel of asthmatics and unaffected controls from US Caucasian, African American, US Hispanic, and Dut

  10. DMPD: Adipose tissue as an immunological organ: Toll-like receptors, C1q/TNFs andCTRPs. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17681884 Adipose tissue as an immunological organ: Toll-like receptors, C1q/TNFs an...ng) (.svg) (.html) (.csml) Show Adipose tissue as an immunological organ: Toll-like receptors, C1q/TNFs andC...TRPs. PubmedID 17681884 Title Adipose tissue as an immunological organ: Toll-like

  11. Deficiency of ATP2C1, a golgi ion pump, induces secretory pathway defects in endoplasmic reticulum ( ER)-associated degradation and sensitivity to ER stress

    NARCIS (Netherlands)

    Ramos-Castaneda, J; Park, YN; Liu, M; Hauser, K; Rudolph, H; Shull, GE; Jonkman, MF; Mori, K; Ikeda, S; Ogawa, H; Arvan, P

    2005-01-01

    Relatively few clues have been uncovered to elucidate the cell biological role(s) of mammalian ATP2C1 encoding an inwardly directed secretory pathway Ca2+/Mn2+ pump that is ubiquitously expressed. Deficiency of ATP2C1 results in a human disease ( Hailey-Hailey), which primarily affects keratinocytes

  12. 多维双极Euler-Poisson方程的C1解的整体存在性%GLOBAL EXISTENCE OF C1-SOLUTIONS TO THE MULTIDIMENSIONAL BIPOLAR EULER-POISSON SYSTEM

    Institute of Scientific and Technical Information of China (English)

    周芳

    2012-01-01

    In this paper,we study a multi-dimensional bipolar Euler-Poisson system (hydrodynamic model) from semiconductor devices or plasmas.Using Littlewood-Paley analysis and energy estimates,we obtain the global well-posedness of classical solutions to the initial value problems in Besov space.Moreover,we also prove that the vorticitics of velocities converge to zero exponentially in the 2D and 3D spaces.%本文研究了出现在半导体器件或者等离子中的多维双极Euler-Poisson方程,证明了它的初值问题的C1解在Besov空间的整体存在性,同时也得到了在二维和三维情形下,速度的璇度以指数的速率收敛到零.

  13. 家族性慢性良性天疱疮ATP2C1基因突变分析%Analysis on Mutations of ATP2C1 Gene in Patients with Hailey-Hailey Disease in China

    Institute of Scientific and Technical Information of China (English)

    李晓莉; 张鼎伟; 肖生祥; 彭振辉

    2012-01-01

    Objective To identify the pathogenic mutations of ATPICI gene in Chinese patients with Hailey-Hailey disease ( HHD). Methods Genomic DNA was extracted from perpheral blood leukocytes. Techniques of PCR and direct sequencing were used to detect the mutations on all 27 exons of ATP2CX gene in Chinese patients with HHD. The previous reports of HHD mutations in last 12 years were collected and summarized. Results We identified four novel mutations including 118-2A→G,K866T,S212X and 356fs2X. Our findings indicated that mutations were distributed more around function regions than others. Notably there was an Asian unique mutated region in the exon 22. Conclusion The four novel mutations is the underlying cause of HHD, which could affect the result of transcription and translation so as to alter the functions of protein encoded by ATP2Cl gene.%目的 探讨家族性慢性良性天疱疮( Hailey-Hailey disease,HHD)患者ATP2C1基因的突变情况.方法 应用外周血DNA抽提、PCR和DNA直接测序等方法对中国非同族的2个HHD家系和2例散发患者的ATP2C1基因的27个外显子进行突变检测,并利用Pubmed和中国学术文献网络出版总库检索最近12年来国内外有关HHD患者ATP2C1基因突变分析的文献,统计分析结果.结果 入组者发现1例剪切突变118-2A→G,1例错义突变K866T,1例无义突变S212X和1例缺失移码突变356fs2X.综述文献发现ATP2C1基因突变主要集中于3个功能区,此外还发现22外显子是亚洲人种HHD的高风险位点.结论 这4例的突变方式目前国内外尚未见报道,可影响转录和翻译的结果,是造成相应家系和散发患者临床病变的特异突变.

  14. Primary structure of human corticosteroid binding globulin, deduced from hepatic and pulmonary cDNAs, exhibits homology with serine protease inhibitors

    International Nuclear Information System (INIS)

    The authors have isolated and sequenced cDNAs for corticosteroid binding globulin (CBG) prepared from human liver and lung mRNAs. The results indicate that CBG mRNA is relatively abundant in the liver but is also present in the lung, testis, and kidney. The liver CBG cDNA contains an open reading frame for a 405-amino acid (M/sub r/ 45,149) polypeptide. This includes a predominantly hydrophobic, leader sequence of 22 residues that precedes the known NH2-terminal sequence of human CBG. We, therefore, predict that the mature protein is composed of 383 amino acids and is a polypeptide of M/sub r/ 42,646. A second, in-frame, 72-base-pair cistron of unknown significance exists between the TAA termination codon for CBG and a possible polyadenylylation signal (AATAAA) located 16 nucleotides before the polyadenylylation site. The deduced amino acid sequence of mature CBG contains two cysteine residues and consensus sequences for the attachment of six possible N-linked oligosaccharide chains. The sequences of the human lung and liver CBG cDNAs differ by only one nucleotide within the proposed leader sequence,and they attribute this to a point mutation. No sequence homology was found between CBG and other steroid binding proteins, but there is a remarkable similarity between the amino acid sequences of CBG and of α1-antitrypsin, and this extends to other members of the serpin (serine protease inhibitor) superfamily

  15. Low-energy tail of the giant dipole resonance in Mo98 and Mo100 deduced from photon-scattering experiments

    Science.gov (United States)

    Rusev, G.; Schwengner, R.; Dönau, F.; Erhard, M.; Grosse, E.; Junghans, A. R.; Kosev, K.; Schilling, K. D.; Wagner, A.; Bečvář, F.; Krtička, M.

    2008-06-01

    Dipole-strength distributions in the nuclides Mo98 and Mo100 up to the neutron-separation energies have been studied in photon-scattering experiments at the bremsstrahlung facility of the Forschungszentrum Dresden-Rossendorf. To determine the dipole-strength distributions up to the neutron-emission thresholds, statistical methods were developed for the analysis of the measured spectra. The measured spectra of scattered photons were corrected for detector response and atomic background by simulations using the code GEANT3. Simulations of γ-ray cascades were performed to correct the intensities of the transitions to the ground state for feeding from higher-lying levels and to determine their branching ratios. The photoabsorption cross sections obtained for Mo98 and Mo100 from the present (γ,γ') experiments are combined with (γ,n) data from literature, resulting in a photoabsorption cross section covering the range from 4 to about 15 MeV of interest for network calculations in nuclear astrophysics. Novel information about the low-energy tail of the giant dipole resonance and its energy dependence is derived. The photoabsorption cross sections deduced from the present photon-scattering experiments are compared with existing data from neutron capture and He3-induced reactions.

  16. cDNA and deduced primary structure of basic phospholipase A2 with neurotoxic activity from the venom secretion of the Crotalus durissus collilineatus rattlesnake

    Directory of Open Access Journals (Sweden)

    F.H.R. Fagundes

    2010-03-01

    Full Text Available To illustrate the construction of precursor complementary DNAs, we isolated mRNAs from whole venom samples. After reverse transcription polymerase chain reaction (RT-PCR, we amplified the cDNA coding for a neurotoxic protein, phospholipase A2 D49 (PLA2 D49, from the venom of Crotalus durissus collilineatus (Cdc PLA2. The cDNA encoding Cdc PLA2 from whole venom was sequenced. The deduced amino acid sequence of this cDNA has high overall sequence identity with the group II PLA2 protein family. Cdc PLA2 has 14 cysteine residues capable of forming seven disulfide bonds that characterize this group of PLA2 enzymes. Cdc PLA2 was isolated using conventional Sephadex G75 column chromatography and reverse-phase high performance liquid chromatography (RP-HPLC. The molecular mass was estimated using matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF mass spectrometry. We tested the neuromuscular blocking activities on chick biventer cervicis neuromuscular tissue. Phylogenetic analysis of Cdc PLA2 showed the existence of two lines of N6-PLA2, denominated F24 and S24. Apparently, the sequences of the New World’s N6-F24-PLA2 are similar to those of the agkistrodotoxin from the Asian genus Gloydius. The sequences of N6-S24-PLA2 are similar to the sequence of trimucrotoxin from the genus Protobothrops, found in the Old World.

  17. A hantavirus causing hemorrhagic fever with renal syndrome requires gC1qR/p32 for efficient cell binding and infection

    International Nuclear Information System (INIS)

    Hantaan virus (HTNV) is a pathogenic hantavirus that causes hemorrhagic fever with renal syndrome (HFRS). HTNV infection is mediated by αvβ3 integrin. We used protein blots of Vero E6 cell homogenates to demonstrate that radiolabeled HTNV virions bind to gC1qR/p32, the acidic 32-kDa protein known as the receptor for the globular head domain of complement C1q. RNAi-mediated suppression of gC1qR/p32 markedly reduced HTNV binding and infection in human lung epithelial A549 cells. Conversely, transient expression of either simian or human gC1qR/p32 rendered non-permissive CHO cells susceptible to HTNV infection. These results suggest an important role for gC1qR/p32 in HTNV infection and pathogenesis

  18. Mitochondrial genome sequencing in Mesolithic North East Europe Unearths a new sub-clade within the broadly distributed human haplogroup C1.

    Directory of Open Access Journals (Sweden)

    Clio Der Sarkissian

    Full Text Available The human mitochondrial haplogroup C1 has a broad global distribution but is extremely rare in Europe today. Recent ancient DNA evidence has demonstrated its presence in European Mesolithic individuals. Three individuals from the 7,500 year old Mesolithic site of Yuzhnyy Oleni Ostrov, Western Russia, could be assigned to haplogroup C1 based on mitochondrial hypervariable region I sequences. However, hypervariable region I data alone could not provide enough resolution to establish the phylogenetic relationship of these Mesolithic haplotypes with haplogroup C1 mitochondrial DNA sequences found today in populations of Europe, Asia and the Americas. In order to obtain high-resolution data and shed light on the origin of this European Mesolithic C1 haplotype, we target-enriched and sequenced the complete mitochondrial genome of one Yuzhnyy Oleni Ostrov C1 individual. The updated phylogeny of C1 haplogroups indicated that the Yuzhnyy Oleni Ostrov haplotype represents a new distinct clade, provisionally coined "C1f". We show that all three C1 carriers of Yuzhnyy Oleni Ostrov belong to this clade. No haplotype closely related to the C1f sequence could be found in the large current database of ancient and present-day mitochondrial genomes. Hence, we have discovered past human mitochondrial diversity that has not been observed in modern-day populations so far. The lack of positive matches in modern populations may be explained by under-sampling of rare modern C1 carriers or by demographic processes, population extinction or replacement, that may have impacted on populations of Northeast Europe since prehistoric times.

  19. The functional integrity of the serpin domain of C1-inhibitor depends on the unique N-terminal domain, as revealed by a pathological mutant.

    Science.gov (United States)

    Bos, Ineke G A; Lubbers, Yvonne T P; Roem, Dorina; Abrahams, Jan Pieter; Hack, C Erik; Eldering, Eric

    2003-08-01

    C1-inhibitor (C1-Inh) is a serine protease inhibitor (serpin) with a unique, non-conserved N-terminal domain of unknown function. Genetic deficiency of C1-Inh causes hereditary angioedema. A novel type of mutation (Delta 3) in exon 3 of the C1-Inh gene, resulting in deletion of Asp62-Thr116 in this unique domain, was encountered in a hereditary angioedema pedigree. Because the domain is supposedly not essential for inhibitory activity, the unexpected loss-of-function of this deletion mutant was further investigated. The Delta 3 mutant and three additional mutants starting at Pro76, Gly98, and Ser115, lacking increasing parts of the N-terminal domain, were produced recombinantly. C1-Inh76 and C1-Inh98 retained normal conformation and interaction kinetics with target proteases. In contrast, C1-Inh115 and Delta 3, which both lack the connection between the serpin and the non-serpin domain via two disulfide bridges, were completely non-functional because of a complex-like and multimeric conformation, as demonstrated by several criteria. The Delta 3 mutant also circulated in multimeric form in plasma from affected family members. The C1-Inh mutant reported here is unique in that deletion of an entire amino acid stretch from a domain not shared by other serpins leads to a loss-of-function. The deletion in the unique N-terminal domain results in a "multimerization phenotype" of C1-Inh, because of diminished stability of the central beta-sheet. This phenotype, as well as the location of the disulfide bridges between the serpin and the non-serpin domain of C1-Inh, suggests that the function of the N-terminal region may be similar to one of the effects of heparin in antithrombin III, maintenance of the metastable serpin conformation. PMID:12773530

  20. A study of TaxC1-x coatings deposited on biomedical 316L stainless steel by radio-frequency magnetron sputtering

    International Nuclear Information System (INIS)

    In this paper, TaxC1-x coatings were deposited on 316L stainless steel (316L SS) by radio-frequency (RF) magnetron sputtering at various substrate temperatures (Ts) in order to improve its corrosion resistance and hemocompatibility. XRD results indicated that Ts could significantly change the microstructure of TaxC1-x coatings. When Ts was xC1-x coatings were in amorphous condition, whereas when Ts was ≥150 deg. C, TaC phase was formed, exhibiting in the form of particulates with the crystallite sizes of about 15-25 nm (Ts = 300 deg. C). Atomic force microscope (AFM) results showed that with the increase of Ts, the root-mean-square (RMS) values of the TaxC1-x coatings decreased. The nano-indentation experiments indicated that the TaxC1-x coating deposited at 300 deg. C had a higher hardness and modulus. The scratch test results demonstrated that TaxC1-x coatings deposited above 150 deg. C exhibited good adhesion performance. Tribology tests results demonstrated that TaxC1-x coatings exhibited excellent wear resistance. The results of potentiodynamic polarization showed that the corrosion resistance of the 316L SS was improved significantly because of the deposited TaxC1-x coatings. The platelet adhesion test results indicated that the TaxC1-x coatings deposited at Ts of 150 deg. C and 300 deg. C possessed better hemocompatibility than the coating deposited at Ts of 25 deg. C. Additionally, the hemocompatibility of the TaxC1-x coating on the 316L SS was found to be influenced by its surface roughness, hydrophilicity and the surface energy.

  1. Relation between axon morphology in C1 spinal cord and spatial properties of medial vestibulospinal tract neurons in the cat.

    Science.gov (United States)

    Perlmutter, S I; Iwamoto, Y; Barke, L F; Baker, J F; Peterson, B W

    1998-01-01

    Twenty-one secondary medial vestibulospinal tract neurons were recorded intraaxonally in the ventromedial funiculi of the C1 spinal cord in decerebrate, paralyzed cats. Antidromic stimulation in C6 and the oculomotor nucleus identified the projection pattern of each neuron. Responses to sinusoidal, whole-body rotations in many planes in three-dimensional space were characterized before injection of horseradish peroxidase or Neurobiotin. The spatial response properties of 19 neurons were described by a maximum activation direction vector (MAD), which defines the axis and direction of rotation that maximally excites the neuron. The other two neurons had spatio-temporal convergent behavior and no MAD was calculated. Collateral morphologies were reconstructed from serial frontal sections to reveal terminal fields in the C1 gray matter. Axons gave off multiple collaterals that terminated ipsilaterally to the stem axon. Collaterals of individual axons rarely overlapped longitudinally but projected to similar regions in the ventral horn when viewed in transverse sections. The number of primary collaterals in C1 was different for vestibulo-collic, vestibulo-oculo-collic, and C6-projecting neurons: on average one every 1.34, 1.72, and 4.25 mm, respectively. The heaviest arborization and most terminal boutons were seen in the ventral horn, in laminae VIII and IX. Varicosities on terminal branches in lamina IX were observed adjacent to large cell bodies-putative neck motoneurons-in counterstained tissue. Some collaterals had branches that extended dorsally to lamina VII. Neurons with different spatial properties had terminal fields in different regions of the ventral horn. Axons with type I responses and MADs near those of a semicircular canal pair had widely distributed collateral branches and numerous terminations in the dorsomedial, ventromedial, and spinal accessory nuclei and in lamina VIII. Axons with type I responses that suggested convergent canal pair input, with

  2. Glycyrrhizic acid prevents astrocyte death by neuromyelitis optica-specific IgG via inhibition of C1q binding.

    Science.gov (United States)

    Kim, Ji-Sun; Cheon, Soyoung; Kim, Seung Woo; Kim, Boram; Kim, Heejaung; Park, Ki Duk; Kim, Sung-Min

    2016-09-16

    Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system and is mediated by complement-dependent cytotoxicity (CDC) of NMO-specific immunoglobulin G (IgG) antibodies (NMO-IgG). Glycyrrhizic acid (GA) has numerous pharmacological effects including inhibition of the complement pathway. We aimed to study the influence of GA on NMO-IgG-induced CDC. NMO-IgG samples from 7 patients with NMO, together with human complement, induced CDC in an aquaporin 4 M23-overexpressing glial cell line, an in vitro NMO model. GA attenuated NMO-IgG-induced CDC in a dose-dependent manner. The mechanism of the GA-related CDC inhibition was sequentially dissected and found to involve inhibition of C1q binding to NMO-IgG. Consequently, GA attenuates NMO-IgG-induced CDC and may be a promising novel therapeutic agent against NMO. PMID:27462020

  3. Niemann-Pick C1-Like 1 (NPC1L1) Protein in Intestinal and Hepatic Cholesterol Transport

    Science.gov (United States)

    Jia, Lin; Betters, Jenna L.; Yu, Liqing

    2014-01-01

    Increased blood cholesterol is an independent risk factor for atherosclerotic cardiovascular disease. Cholesterol homeostasis in the body is controlled mainly by endogenous synthesis, intestinal absorption, and hepatic excretion. Niemann-Pick C1-Like 1 (NPC1L1) is a polytopic transmembrane protein localized at the apical membrane of enterocytes and the canalicular membrane of hepatocytes. It functions as a sterol transporter to mediate intestinal cholesterol absorption and counterbalances hepatobiliary cholesterol excretion. NPC1L1 is the molecular target of ezetimibe, a potent cholesterol absorption inhibitor that is widely used in treating hypercholesterolemia. Recent findings suggest that NPC1L1 deficiency or ezetimibe treatment also prevents diet-induced hepatic steatosis and obesity in addition to reducing blood cholesterol. Future studies should focus on molecular mechanisms underlying NPC1L1-dependent cholesterol transport and elucidation of how a cholesterol transporter modulates the pathogenesis of metabolic diseases. PMID:20809793

  4. Critical regions with central charge c=1/2,7/10,4/5 in the spin-1 quantum chain

    International Nuclear Information System (INIS)

    The phase diagramm of the Blume-Emery-Griffiths spin-1-quantum chain is calculated by finite-size scaling with respect to all four parameters. We locate the three-dimensional critical manifold and determine a two-dimensional tricritical surface where the spectra exhibit conformal invariance corresponding to the central charges c=7/10 and 4/5. Choosing one parameter to be zero, we can treat the model analytically and from this the spectrum on a large part of the Ising-like critical region can be understood: there the spectrum consists of conformal c=1/2-levels on which a massive spectrum is superimposed. Calculating three-point functions we study which perturbations by primary fields lead from c=4/5 or c=7/10-critical points to Ising-type regions. (orig.)

  5. IUPAC-NIST Solubility Data Series. 101. Alcohols + Hydrocarbons + Water Part 3. C1-C3 Alcohols + Aromatic Hydrocarbons

    Science.gov (United States)

    Oracz, Paweł; Góral, Marian; Wiśniewska-Gocłowska, Barbara; Shaw, David G.; Mączyński, Andrzej

    2016-09-01

    The mutual solubilities and related liquid-liquid equilibria for 11 ternary systems of C1-C3 alcohols with aromatic hydrocarbons and water are exhaustively and critically reviewed. Reports of experimental determination of solubility that appeared in the primary literature prior to the end of 2012 are compiled. For nine systems, sufficient data are available (two or more independent determinations) to allow critical evaluation. All new data are expressed as mass percent and mole fraction as well as the originally reported units. In addition to the standard evaluation criteria used throughout the Solubility Data Series, an additional criterion was used for each of the evaluated systems. These systems include one binary miscibility gap in the hydrocarbon + water subsystem. The binary tie lines were compared with the recommended values published previously.

  6. IUPAC-NIST Solubility Data Series. 101. Alcohols + Hydrocarbons + Water. Part 2. C1-C3 Alcohols + Aliphatic Hydrocarbons

    Science.gov (United States)

    Oracz, Paweł; Góral, Marian; Wiśniewska-Gocłowska, Barbara; Shaw, David G.; Mączyński, Andrzej

    2016-09-01

    The mutual solubilities and related liquid-liquid equilibria for 37 ternary systems of C1-C3 alcohols with aliphatic hydrocarbons and water are exhaustively and critically reviewed. Reports of experimental determination of solubility that appeared in the primary literature prior to the end of 2012 are compiled. For 14 systems, sufficient data are available (two or more independent determinations) to allow critical evaluation. All data are expressed as mass percent and mole fraction as well as the originally reported units. In addition to the standard evaluation criteria used throughout the Solubility Data Series, an additional criterion was used for each of the evaluated systems. These systems include one binary miscibility gap in the hydrocarbon + water subsystem and another one can be in the methanol + hydrocarbon subsystem. The binary tie lines were compared with the recommended values published previously.

  7. Niemann-Pick C1 like 1 gene expression is down-regulated by LXR activators in the intestine

    International Nuclear Information System (INIS)

    Niemann-Pick C1 like 1 (NPC1L1) is a protein critical for intestinal cholesterol absorption. The nuclear receptors peroxisome proliferator-activated receptor alpha (PPARα) and liver X receptors (LXRα and LXRβ) are major regulators of cholesterol homeostasis and their activation results in a reduced absorption of intestinal cholesterol. The goal of this study was to define the role of PPARα and LXR nuclear receptors in the regulation of NPC1L1 gene expression. We show that LXR activators down-regulate NPC1L1 mRNA levels in the human enterocyte cell line Caco-2/TC7, whereas PPARα ligands have no effect. Furthermore, NPC1L1 mRNA levels are decreased in vivo, in duodenum of mice treated with the LXR agonist T0901317. In conclusion, the present study identifies NPC1L1 as a novel LXR target gene further supporting a crucial role of LXR in intestinal cholesterol homeostasis

  8. Induction of quinone reductase activity by psoralidin isolated from Psoralea corylifolia in mouse hepa 1c1c7 cells.

    Science.gov (United States)

    Lee, Sung-Jin; Nam, Kung-Woo; Mar, Woongchon

    2009-07-01

    Quinone reductase (QR) is a protective phase II enzyme against mutagens and carcinogens which is inducible by a number of chemical compounds in plants. This study was carried out to investigate effects of the fractions from the seeds of Psoralea corylifolia on the induction of QR with Hepa 1c1c7 murine hepatoma cell line. The ethyl acetate-soluble fraction of the methanolic extract from the seeds was found to induce QR and the concentration of 1.5 fold QR induction (1.5 FIC) was 1.2 mug/mL. We obtained as an active compound, psoralidin, isolated from the ethyl acetate-soluble fraction after further sequential fractionation with column chromatography and 1.5 FIC of psoralidin was 0.5 mug/mL. The seeds of Psoralea corylifolia and psoralidin might be a candidate for developing QR inducers. PMID:19641888

  9. Induction of quinone reductase activity by stilbene analogs in mouse Hepa 1c1c7 cells.

    Science.gov (United States)

    Heo, Y H; Kim, S; Park, J E; Jeong, L S; Lee, S K

    2001-12-01

    Based on the potential cancer chemopreventive activity of resveratrol, a trihydroxystilbene with the induction of quinone reductase activity, this study was designed to determine if stilbene-related compounds were inducers of phase II detoxifying metabolic enzyme quinone reductase (QR) in the mouse hepatoma Hepa 1c1c7 cells. Among the thirteen compounds tested, several compounds including 3,4,5,3',5'-pentamethoxy-trans-stilbene were found to potentially induce QR activity in this cell line. In addition, substitution with 3-thiofurane ring instead of phenyl ring in the stilbene skeleton also exhibited potential induction of QR activity. This result will give primary information to design the potential inducers of QR activity in the stilbene analogs. PMID:11794542

  10. Differential regulation of polysome mRNA levels in mouse Hepa-1C1C7 cells exposed to dioxin.

    Science.gov (United States)

    Thornley, Jessica A; Trask, Heidi W; Ridley, Christian J A; Korc, Murray; Gui, Jiang; Ringelberg, Carol S; Wang, Sinny; Tomlinson, Craig R

    2011-10-01

    The environmental agent 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin) causes a multitude of human illnesses. In order to more fully understand the underlying biology of TCDD toxicity, we tested the hypothesis that new candidate genes could be identified using polysome RNA from TCDD-treated mouse Hepa-1c1c7 cells. We found that (i) differentially expressed whole cell and cytoplasm RNA levels are both poor predictors of polysome RNA levels; (ii) for a majority of RNAs, differential RNA levels are regulated independently in the nucleus, cytoplasm, and polysomes; (iii) for the remaining polysome RNAs, levels are regulated via several different mechanisms, including a "tagging" of mRNAs in the nucleus for immediate polysome entry; and (iv) most importantly, a gene list derived from differentially expressed polysome RNA generated new genes and cell pathways potentially related to TCDD biology. PMID:21570461

  11. Effects of rutaecarpine on hydrogen peroxide-induced apoptosis in murine hepa-1c1c7 cells.

    Science.gov (United States)

    Lee, Sung-Jin; Ahn, Hyunjin; Nam, Kung-Woo; Kim, Kyeong Ho; Mar, Woongchon

    2012-09-01

    The aim of this study was to investigate the inhibitory effects of rutaecarpine on DNA strand breaks and apoptosis induced by hydrogen peroxide (H2O2) in murine Hepa-1c1c7 cells. Oxidative DNA damage was estimated by nuclear condensation assessment, fluorescence-activated cell sorting analysis, and Comet assay. Rutaecarpine inhibited cell death induced by 500 μM H2O2, as assessed by 4',6-diamidino-2-phenylindole (DAPI) staining. Treatment with rutaecarpine reduced the number of DNA strand breaks induced by H2O2, as assessed by DAPI staining and Comet assay, and increased quinone reductase, phosphatidylinositol 3-kinase, and pAkt protein levels, as assessed by western blotting. PMID:24009839

  12. Identification and characterization of a novel gene, c1orf109, encoding a CK2 substrate that is involved in cancer cell proliferation

    Directory of Open Access Journals (Sweden)

    Liu Shan-shan

    2012-05-01

    Full Text Available Abstract Background In the present study we identified a novel gene, Homo Sapiens Chromosome 1 ORF109 (c1orf109, GenBank ID: NM_017850.1, which encodes a substrate of CK2. We analyzed the regulation mode of the gene, the expression pattern and subcellular localization of the predicted protein in the cell, and its role involving in cell proliferation and cell cycle control. Methods Dual-luciferase reporter assay, chromatin immunoprecipitation and EMSA were used to analysis the basal transcriptional requirements of the predicted promoter regions. C1ORF109 expression was assessed by western blot analysis. The subcellular localization of C1ORF109 was detected by immunofluorescence and immune colloidal gold technique. Cell proliferation was evaluated using MTT assay and colony-forming assay. Results We found that two cis-acting elements within the crucial region of the c1orf109 promoter, one TATA box and one CAAT box, are required for maximal transcription of the c1orf109 gene. The 5′ flanking region of the c1orf109 gene could bind specific transcription factors and Sp1 may be one of them. Employing western blot analysis, we detected upregulated expression of c1orf109 in multiple cancer cell lines. The protein C1ORF109 was mainly located in the nucleus and cytoplasm. Moreover, we also found that C1ORF109 was a phosphoprotein in vivo and could be phosphorylated by the protein kinase CK2 in vitro. Exogenous expression of C1ORF109 in breast cancer Hs578T cells induced an increase in colony number and cell proliferation. A concomitant rise in levels of PCNA (proliferating cell nuclear antigen and cyclinD1 expression was observed. Meanwhile, knockdown of c1orf109 by siRNA in breast cancer MDA-MB-231 cells confirmed the role of c1orf109 in proliferation. Conclusions Taken together, our findings suggest that C1ORF109 may be the downstream target of protein kinase CK2 and involved in the regulation of cancer cell proliferation.

  13. Development of a global LAI/ FAPAR estimation algorithm for JAXA's new earth observation satellite,GCOM-C1

    Science.gov (United States)

    Ono, Y.; Murakami, H.; Kobayashi, H.; Nasahara, K.; Kajiwara, K.; Honda, Y.

    2013-12-01

    Japan Aerospace eXploration Agency (JAXA) is planning to launch a new earth observation satellite, GCOM-C1 (Global Change Observation Mission 1st-Climate) in the Japanese Fiscal Year 2016. SGLI (Second generation GLobal Imager) is a radiometer, which has 17 channels from near ultraviolet to thermal infrared. Furthermore, it has the features, such as 250m spatial resolution, polarization, and multi-angle observation. In the GCOM-C1 land science team, vegetation index, above ground biomass, LAI (Leaf Area Index), FAPAR (Fraction of Absorbed Photosynthetically Active Radiation), etc. are scheduled to be generated from SGLI data as standard products. These are important in order to estimate terrestrial carbon cycle. In this study, we propose a new LAI and FAPAR estimation algorithm from SGLI data and the proposed algorithm was applied to Terra/ MODIS data. The relation between LAI and BRF (Bidirectional Reflectance Factor) in red and near infrared bands or FAPAR are dependent on crown cover ratio. Therefore, LUT (Look Up Table) of crown cover ratio, LAI and BRF in red and near infrared or FAPAR are created by FLiES which is 3-dimensional radiative transfer model (Kobayashi, H. and H. Iwabuchi (2008), A coupled 1-D atmosphere and 3-D canopy radiative transfer model for canopy reflectance, light environment, and photosynthesis simulation in a heterogeneous landscape, Remote Sensing of Environment, 112, 173-185). First, crown cover ratio is estimated from multiple land surface reflecntace in red and near infrared bands based on LUT of BRF in red and near infrared bands. Next, LAI and FAPAR are estimated from land surface reflectance in red and near infrared band based on estimated crown cover ratio and LUT of BRF in red and near infrared and FAPAR. As a result of applying Terra/ MODIS land surface reflectance product (MOD09), estimated LAI and FAPAR agreed with LAI and FAPAR observed at the AmeriFlux sites.

  14. Dynamic stereochemistry of erigeroside by measurement of 1H- 1H and 13C- 1H coupling constants

    Science.gov (United States)

    Tafazzoli, Mohsen; Ghiasi, Mina; Moridi, Mahdi

    2008-07-01

    Erigeroside was extracted from Satureja khuzistanica Jamzad (Marzeh Khuzistani in Persian, family of lamiaceae), and 1H, 13C, 13C{ 1H}, 1H- 1H COSY, HMQC and J-HMBC were obtained to identify this compound and determine a complete set of J-coupling constants ( 1JC-H, 2JC-H, 3JC-H and 3JH-H) values within the exocyclic hydroxymethyl group (CH 2OH) and anomeric center. In parallel, density functional theory (DFT) using B3LYP functional and split-valance 6-311++G** basis set has been used to optimized the structures and conformers of erigeroside. In all calculations solvent effects were considered using a polarized continuum (overlapping spheres) model (PCM). The dependencies of 1J, 2J and 3J involving 1H and 13C on the C 5'-C 6' ( ω), C 6'-O 6' ( θ) and C 1'-O 1' ( φ) torsion angles in erigeroside were computed using DFT method. Complete hyper surfaces for 1JC1',H1', 2JC5',H6'R, 2JC5',H6'S, 2JC6',H5', 3JC4',H6'R, 3JC4',H6'S and 2JH6'R-H5'S as well as 3JH5',H6'R were obtained and used to derive Karplus equations to correlate these couplings to ω, θ and φ. These calculated J-couplings are in agreement with experimental values. These results confirm the reliability of DFT calculated coupling constants in aqueous solution.

  15. [A case report of hereditary angioedema and studies on the serum components of complement, C1-inactivator and proteinase inhibitors during edema attack].

    Science.gov (United States)

    Mikami, A; Kohno, M

    1987-05-01

    Sixteen years old girl was admitted because of for the past ten years' frequent edema attack and abdominal pain. Laboratory examination revealed hypocomplementemia, marked depletion of the fourth component of complement and low level of C1-inactivator. Familial studies revealed that her mother was also hypocomplementemic and in low level of C1-inactivator. Serial studies performed on the alterlation of components of complement, C1-inactivator, alpha 1-antitrypsin, antithrombin III, and alpha 2-macroglobulin during edema attack. The fourth component of complement and C1-inactivator were markedly depleted in remission and attack. Remarkable depletion was found in antithrombin III and esterase inhibition activity of C1-inactivator during attack. In contrast, alpha 1-antitrypsin and alpha 2-macroglobulin did not change. The present study may explain that Hageman factor fragments, activated by C1s, promotes kinin generation via kalikrein activation. And the condition that complete functional deficiency of C1-inactivator was main role in this circuit. Fibrynolysis and late components of complement was less influence on edema attack. PMID:3610041

  16. Cinryze as the first approved C1 inhibitor in the USA for the treatment of hereditary angioedema: approval, efficacy and safety.

    Science.gov (United States)

    Lunn, Michael; Santos, Carah; Craig, Timothy

    2010-01-01

    Hereditary angioedema (HAE) is a clinical disorder characterized by a deficiency of C1 esterase inhibitor (C1-INH). HAE has traditionally been divided into two subtypes. Unique among the inherited deficiencies of the complement system, HAE Types I and II are inherited as an autosomal dominant disorder. The generation of an HAE attack is caused by the depletion and/or consumption of C1-inhibitor manifested as subcutaneous or submucosal edema of the upper airway, face, extremities, or gastrointestinal tract. Attacks can be severe and potentially life-threatening, particularly with laryngeal involvement. Despite the availability of C1-INH for the treatment of HAE since the 1980s in Europe and other countries, HAE treatment in the United States was limited to androgen therapy. The human plasma-derived C1 esterase inhibitor (Cinryze™), distributed by Lev Pharmaceuticals, was approved in October 2008 for the prevention of HAE attacks based on the results of a phase III clinical trial. This review aims to describe the history of C1-INH replacement in HAE as well as the pharmacology, efficacy and safety of C1-INH, concentrating on Cinryze as the first approved chronic replacement treatment for the prophylaxis of HAE attacks. PMID:22282695

  17. How to deduce and teach the logical and unambiguous answer, namely L = ∑C, to "What is Life?" using the principles of communication?

    Science.gov (United States)

    De Loof, Arnold

    2015-01-01

    Is it possible to understand the very nature of 'Life' and 'Death' based on contemporary biology? The usual spontaneous reaction is: "No way. Life is far too complicated. It involves both material- and an immaterial dimensions, and this combination exceeds the capacities of the human brain." In this paper, a fully contrarian stand is taken. Indeed it will be shown that without invoking any unknown principle(s) unambiguous definitions can be logically deduced. The key? First ask the right questions. Next, thoroughly imbue contemporary biology with the principles of communication, including both its 'hardware' and its 'software' aspects. An integrative yet simple principle emerges saying that: 1. All living matter is invariably organized as sender-receiver compartments that incessantly handle and transfer information (= communicate); 2. The 'communicating compartment' is better suited to serve as universal unit of structure, function and evolution than 'the (prokaryotic) cell', the smallest such unit; 3. 'Living matter' versus 'non-living' are false opposites while 'still alive' and 'just not alive anymore' are true opposites; 4. 'Death' ensues when a given sender-receiver compartment irreversibly loses its ability to handle information at its highest level of compartmental organization; 5. The verb 'Life' (L) denotes nothing else than the total sum (∑) of all acts of communication (C) executed by a sender-receiver at all its levels of compartmental organization: L = ∑C; 6. Any act of communication is a problem-solving act; 6. Any Extended Evolutionary Synthesis (EES) should have the definition of Life at its core. PMID:27064373

  18. Structural and dynamic aspects of binding of prototype lexitropsin to the decadeoxyribonucleotide d(CGCAATTGCC)2 deduced from high-resolution 1H NMR studies

    International Nuclear Information System (INIS)

    Structural and dynamic properties of the self-complementary decadeoxyribonucleotide d-(CGCAATTGCC)2 and the interaction between a prototype lexitropsin, or information-reading oligopeptide, and the decadeoxyribonucleotide and are deduced by using high-resolution 1H NMR techniques. The nonexchangeable and imino proton resonances of d(CGCAATTGCG)2 have been completely assigned by two-dimensional NMR studies. The decadeoxyribonucleotide exists as a right-handed B-DNA. In the 1H NMR spectrum of the l:1 complex, the selective chemical shifts and removal of degeneracy of AH2(4), AH2(5), T-CH3(6), and T-CH3(7) due to the anisotropy effects of the heterocyclic moieties of the ligand, and with lesser effects at the flanking base sites C(3) and G(8), locate the drug centrally in the decadeoxyribonucleotide. This conclusion is supported by plots of individual chemical shift changes across the decadeoxyribonucleotide. Strong nuclear Overhauser effects (NOEs) between pyrrol H5 and AH2(5), and weaker NOEs to AH1'(5), TH3'(6), and AH2'(5), firmly locate the ligand in the minor groove. Intraligand NOEs between the adjacent heterocyclic moieties indicate that the lexitropsin is subject to propeller twisting about the N6-C9 bond in both the bound and free forms. Nuclear Overhauser effect spectroscopy (NOESY) and correlated spectroscopy (COSY) experiments also indicate that the removal of degeneracy of the C16 methylene protons upon complexation may arise from restricted rotation about the C15-N9, C15-C16, and C16-C17 bonds. NOE measurements on the decadeoxyribonucleotide in the 1:1 complex confirm it exists as a right-handed helix and belongs to the B family. Alternative mechanisms for this exchange process are considered

  19. C1q Modulates the Response to TLR7 Stimulation by Pristane-Primed Macrophages: Implications for Pristane-Induced Lupus.

    Science.gov (United States)

    Carlucci, Francesco; Ishaque, Attia; Ling, Guang Sheng; Szajna, Marta; Sandison, Ann; Donatien, Philippe; Cook, H Terence; Botto, Marina

    2016-02-15

    The complement component C1q is known to play a controversial role in the pathogenesis of systemic lupus erythematosus, but the underlying mechanisms remain poorly understood. Intraperitoneal injection of pristane induces a lupus-like syndrome whose pathogenesis implicates the secretion of type I IFN by CD11b(+) Ly6C(high) inflammatory monocytes in a TLR7-dependent fashion. C1q was also shown to influence the secretion of IFN-α. In this study, we explored whether C1q deficiency could affect pristane-induced lupus. Surprisingly, C1qa(-/-) mice developed lower titers of circulating Abs and milder arthritis compared with the controls. In keeping with the clinical scores, 2 wk after pristane injection the peritoneal recruitment of CD11b(+) Ly6C(high) inflammatory monocytes in C1qa(-/-) mice was impaired. Furthermore, C1q-deficient pristane-primed resident peritoneal macrophages secreted significantly less CCL3, CCL2, CXCL1, and IL-6 when stimulated in vitro with TLR7 ligand. Replenishing C1q in vivo during the pristane-priming phase rectified this defect. Conversely, pristane-primed macrophages from C3-deficient mice did not show impaired cytokine production. These findings demonstrate that C1q deficiency impairs the TLR7-dependent chemokine production by pristane-primed peritoneal macrophages and suggest that C1q, and not C3, is involved in the handling of pristane by phagocytic cells, which is required to trigger disease in this model. PMID:26773156

  20. Phase 1 trial of AMA1-C1/Alhydrogel plus CPG 7909: an asexual blood-stage vaccine for Plasmodium falciparum malaria.

    Directory of Open Access Journals (Sweden)

    Gregory E D Mullen

    Full Text Available BACKGROUND: Apical Membrane Antigen 1 (AMA1, a polymorphic merozoite surface protein, is a leading blood-stage malaria vaccine candidate. This is the first reported use in humans of an investigational vaccine, AMA1-C1/Alhydrogel, with the novel adjuvant CPG 7909. METHODS: A phase 1 trial was conducted at the University of Rochester with 75 malaria-naive volunteers to assess the safety and immunogenicity of the AMA1-C1/Alhydrogel+CPG 7909 malaria vaccine. Participants were sequentially enrolled and randomized within dose escalating cohorts to receive three vaccinations on days 0, 28 and 56 of either 20 microg of AMA1-C1/Alhydrogel+564 microg CPG 7909 (n = 15, 80 microg of AMA1-C1/Alhydrogel (n = 30, or 80 microg of AMA1-C1/Alhydrogel+564 microg CPG 7909 (n = 30. RESULTS: Local and systemic adverse events were significantly more likely to be of higher severity with the addition of CPG 7909. Anti-AMA1 immunoglobulin G (IgG were detected by enzyme-linked immunosorbent assay (ELISA, and the immune sera of volunteers that received 20 microg or 80 microg of AMA1-C1/Alhydrogel+CPG 7909 had up to 14 fold significant increases in anti-AMA1 antibody concentration compared to 80 microg of AMA1-C1/Alhydrogel alone. The addition of CPG 7909 to the AMA1-C1/Alhydrogel vaccine in humans also elicited AMA1 specific immune IgG that significantly and dramatically increased the in vitro growth inhibition of homologous parasites to levels as high as 96% inhibition. CONCLUSION/SIGNIFICANCE: The safety profile of the AMA1-C1/Alhydrogel+CPG 7909 malaria vaccine is acceptable, given the significant increase in immunogenicity observed. Further clinical development is ongoing. TRIAL REGISTRATION: ClinicalTrials.gov NCT00344539.

  1. Surface-bound capsular polysaccharide of type Ia group B Streptococcus mediates C1 binding and activation of the classic complement pathway

    International Nuclear Information System (INIS)

    The role of surface-bound type Ia group B Streptococcus (GBS) capsular polysaccharide in anti-body-independent binding of C1 and activation of the classic component pathway was investigated. In a radiolabeled bacterial-polymorphonuclear leukocyte (PMN) association assay, a measure of bacterial opsonization, preincubation of 3H-type Ia GBS with purified F(ab')2 to the organism blocked the association of the bacteria with PMN', and the inhibitory effect was dose dependent. The specificity of F(ab')2 blocking was shown after adsorption of F(ab')2 with type Ia polysaccharide-sensitized erythrocytes. Polysaccharide-adsorbed F(ab')2 had a 70% decrease in ability to block the association of bacteria with PMN. Neuraminidase digestion removed 80% of the terminal sialic acid residues from the native polysaccharide. These neuraminidase-digested organisms had a 72% decrease in binding and transfer of purified C1 compared with non-enzyme-treated organisms. Type Ia capsular polysaccharide bound to sheep erythrocytes promoted classic complement pathway-mediated hemolysis of the cells. The role of C1 inhibitor (INH) in modulation of C1 activation by the organisms was investigated. The possibility existed that the C1 INH could be bound by the bacteria, allowing C1 activation to occur in the fluid phase. The inhibitor was purified from human serum, and its activity was measured before and after incubation with type Ia GBS. The organisms had no effect on C1 INH activity. Thus surface-bound capsular polysacchardie of type Ia GBS mediates C1 binding and classic pathway activation, and this does not involve the C1 INH

  2. Adsorption and evolution behavior of 4C1Si island configurations on diamond (0 0 1) surface: A first principle study

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xuejie, E-mail: xuejieliu2000@yahoo.com [School of Mechanical Engineering, Inner Mongolia University of Science and Technology, Baotou 014010 (China); Gengdan Institute of Beijing University of Technology, Beijing 101301 (China); Yin, Yongjie; Ren, Yuan; Wei, Huai [School of Mechanical Engineering, Inner Mongolia University of Science and Technology, Baotou 014010 (China)

    2015-01-05

    Highlights: • We investigate the adsorption energy of C-by-3C1Si islands on diamond (0 0 1) surface. • The adsorption energy of Si-by-4C island configurations was calculated by DFT. • The evolution manner from C5-by-3C1Si to Si3-by-4C island were calculated by NEB. - Abstract: The adsorption energy of the 4C1Si island configurations and the diffusion activation energies of carbon and silicon atoms on diamond (0 0 1) surface were calculated with first principle method based on density functional theory (DFT) to study the growth of diamond films and the growth position of silicon particles after they are mixed into the composite film. The 4C1Si island configurations consist of five types of C-by-3C1Si configurations and four types of Si-by-4C configurations. The adsorption energy and total energy of the 4C1Si island configurations were calculated firstly. In addition, the diffusion activation energies of the carbon and silicon atoms were calculated. The results show that: (1) the adsorption energy of the Si-by-4C island configurations is higher than that of the C-by-3C1Si island configurations. This indicates that it is not easy for silicon atoms to remain stable in the 3C1Si island. In contrast, silicon atoms are easy to move out of the island so that the carbon atoms out of the 3C1Si Island can enter the island to form the 4C island; (2) Compared with the carbon atom, silicon atom needs lower diffusion activation energy to move into or out of the island. This shows that silicon atoms are more active than carbon atoms. Thus, it is easier for silicon particles to fill the vacancy defects in diamond/Si films, improving the compactness of the diamond composite films.

  3. Artrodese Cervical C1-C2 pelas técnicas de Harms e Magerl Artrodesis cervical C1-C2 por las técnicas de Harms y Magerl Harms and Magerl types of C1-C2 cervical artrodesis

    OpenAIRE

    Cristina Maria Varino Sousa; Luís Pires Silva; Cláudia Santos; Eurico Silva; José Figueiredo

    2010-01-01

    INTRODUÇÃO: A instabilidade atlantoaxial pode resultar em alterações neurológicas, dor e limitação da mobilidade cervical. É uma situação grave pelo risco de tetraparésia ou morte súbita. Na literatura estão descritas várias técnicas de estabilização cirúrgica C1-C2 e neste artigo foram comentadas com maior ênfase as técnicas de Harms e Magerl, as mais utilizadas em nossa instituição. OBJETIVO: Descrever a casuística das artrodeses atlantoaxiais realizadas nos últimos cinco anos no Centro Hos...

  4. Cloning and characterization of the c1 repressor of Pseudomonas aeruginosa bacteriophage D3: a functional analog of phage lambda cI protein.

    OpenAIRE

    Miller, R V; Kokjohn, T. A.

    1987-01-01

    We cloned the gene (c1) which encodes the repressor of vegetative function of Pseudomonas aeruginosa bacteriophage D3. The cloned gene was shown to inhibit plating of D3 and the induction of D3 lysogens by UV irradiation. The efficiency of plating and prophage induction of the heteroimmune P. aeruginosa phage F116L were not affected by the presence of the cloned c1 gene of D3. When the D3 DNA fragment containing c1 was subcloned into pBR322 and introduced into Escherichia coli, it was shown t...

  5. X-ray Fluorescence Particle Size and Scattering Angle Considerations Preparatory Experiments for the Calibration and Interpretation of C1XS Data

    OpenAIRE

    Weider, S.Z.; Gow, J.; Joy, K. H.; Crawford, I. A.; Smith, D R; Holland, A. D.; Swinyard, B. M.

    2008-01-01

    ISRO’s Chandrayaan-1 mission to the Moon is due to be launched in April 2008. Part of its payload is C1XS, a compact X-ray fluorescence (XRF) spectrometer which will provide high quality elemental mapping of the lunar surface [1]. In flight, the input source (solar X-ray spectrum) will be measured by the accompanying XSM payload [2]. An ‘in-house’ IDL XRF modelling code (referred to as the ‘C1XS XRF code’ [3]), which is based on the methods of [4], will be used to convert the C1XS data from X...

  6. Avaliação de série de pacientes com artrodese C1-C2 Evaluación de diferentes casos con artrodesis C1-C2 Evaluation of different cases with C1-C2 arthrodesis

    Directory of Open Access Journals (Sweden)

    Cesar Salge Ghilardi

    2012-01-01

    Full Text Available OBJETIVO: Análise retrospectiva de prontuários de pacientes com instabilidade C1-C2 de causas traumáticas e não-traumáticas, submetidos à artrodese C1-C2. MÉTODOS: Foi realizada análise retrospectiva de prontuários de 20 pacientes do ambulatório de coluna do IOT-HCFMUSP com idades entre 7 e 83 anos (média de 43 anos, de ambos os sexos. Os parâmetros radiográficos para instabilidade foram baseados na medida do intervalo atlanto-axial superior a 3 mm em adultos e a 5 mm em crianças, utilizando-se medidas obtidas através de radiografia simples analisada no perfil. RESULTADOS: Foram operados 20 pacientes com instabilidade cervical alta, a maioria de origem traumática. A técnica cirúrgica mais utilizada foi a artrodese descrita por Magerl. Não foram observadas lesões vasculares. Foi registrada complicação infecciosa em dois pacientes. Obteve-se uma taxa de consolidação da artrodese de 85% e não foram necessárias cirurgias de revisão. CONCLUSÃO: Todas as técnicas utilizadas produziram a consolidação óssea satisfatória e foram excelentes para controlar a instabilidade atlanto-axial.OBJETIVO: Estudio retrospectivo de fichas depacientes con inestabilidad C1-C2, de causas traumáticas y no traumáticas, quienes se sometieron a artrodesis C1-C2. MÉTODOS: Se realizó un análisis retrospectivo de los historiales clínicos de 20 pacientes externos de la columna en el IOT-HC.FM.USP de edades comprendidas entre 07 y 83 años (promedio de 43 años de ambos sexos. Los parámetros radiológicos de inestabilidad se basaron en la medición del intervalo atlantoaxial superior a 3 mm en adultos y a 5 mm en niños, utilizándose medidas obtenidas a partir de radiografías simples analizadas en el perfil. RESULTADOS: Se operaron 20 pacientes con inestabilidad cervical alta, la mayoría con inestabilidad de origen traumático. La técnica quirúrgica más utilizada fue la artrodesis descrita por Magerl. No se observaron lesiones

  7. Artrodese Cervical C1-C2 pelas técnicas de Harms e Magerl Artrodesis cervical C1-C2 por las técnicas de Harms y Magerl Harms and Magerl types of C1-C2 cervical artrodesis

    Directory of Open Access Journals (Sweden)

    Cristina Maria Varino Sousa

    2010-09-01

    Full Text Available INTRODUÇÃO: A instabilidade atlantoaxial pode resultar em alterações neurológicas, dor e limitação da mobilidade cervical. É uma situação grave pelo risco de tetraparésia ou morte súbita. Na literatura estão descritas várias técnicas de estabilização cirúrgica C1-C2 e neste artigo foram comentadas com maior ênfase as técnicas de Harms e Magerl, as mais utilizadas em nossa instituição. OBJETIVO: Descrever a casuística das artrodeses atlantoaxiais realizadas nos últimos cinco anos no Centro Hospitalar do Porto, particularmente, taxa de consolidações, complicações observadas, reintervenções e comparação com os estudos publicados. MÉTODOS: Estudo retrospectivo, com cinco anos, dos doentes submetidos a artrodese atlantoaxial no Centro Hospitalar do Porto. RESULTADOS: Foram operados 11 doentes no período do estudo, a maioria com instabilidade de causa traumática. O método de artrodese mais utilizado foi o descrito por Magerl. Não foram observadas lesões vasculares. Foram registradas complicações infecciosas em quatro doentes, sendo que essas infecções foram mais comuns em doentes com patologias inflamatórias de base. Obteve-se uma taxa de consolidação da artrodese de 100%; não foram necessárias cirurgias de revisão. CONCLUSÃO: Em nossa série, as artrodeses posteriores pelas técnicas de Harms e de Magerl resultaram em um ótimo controle da instabilidade C1-C2. Doentes com indicação de artrodese por instabilidade reumática apresentaram alta taxa de complicações infecciosas.INTRODUCCIÓN: la inestabilidad atlantoaxial puede resultar en alteraciones neurológicas, dolor y limitación de la movilidad cervical. Es una situación grave por el riesgo de tetraparesia o muerte súbita. En la literatura están descritas varias técnicas de estabilización quirúrgica C1-C2 y en este artículo serán comentadas con mayor énfasis las técnicas de Harms y Magerl, las más utilizadas en nuestra instituci

  8. gC1q-R/p33, a member of a new class of multifunctional and multicompartmental cellular proteins, is involved in inflammation and infection.

    Science.gov (United States)

    Ghebrehiwet, B; Lim, B L; Kumar, R; Feng, X; Peerschke, E I

    2001-04-01

    Human gC1q-R (p33, p32, C1qBP, TAP) is a ubiquitously expressed, multiligand-binding, multicompartmental cellular protein involved in various ligand-mediated cellular responses. Although expressed on the surface of cells, an intriguing feature of the membrane-associated form of gC1q-R is that its translated amino acid sequence does not predict the presence of either a sequence motif compatible with a transmembrane segment or a consensus site for a glycosylphosphatidylinositol anchor. Moreover, the N-terminal sequence of the pre-pro-protein gC1q-R contains a motif that targets the molecule to the mitochondria and as such was deemed unlikely to be expressed on the surface. However, several lines of experimental evidence clearly show that gC1q-R is present in all compartments of the cell, including the extracellular cell surface. First, surface labeling of B lymphocytes with the membrane-impermeable reagent sulfosuccinimidyl 6-(biotinamido)hexanoate shows specific biotin incorporation into the surface-expressed but not the intracellular form of gC1q-R. Second, FACS and confocal laser scanning microscopic analyses using anti-gC1q-R IgG mAb 60.11 or 74.5.2, and the fluorophore Alexa 488-conjugated F(ab')2 goat anti-mouse IgG as a probe, demonstrated specific staining of Raji cells (>95% viable). Three-dimensional analyses of the same cells by confocal microscopy showed staining distribution that was consistent with surface expression. Third, endothelial gC1q-R, which is associated with the urokinase plasminogen activator receptor, and cytokeratin 1 bind 125I-high molecular weight kininogen in a specific manner, and the binding is inhibited dose-dependently by mAb 74.5.2 recognizing gC1q-R residues 204-218. Fourth, native gC1q-R purified from Raji cell membranes but not intracellular gC1q-R is glycosylated, as evidenced by a positive periodic acid Schiff stain as well as sensitivity to digestion with endoglycosidase H and F. Finally, cross-linking experiments using C1q

  9. Re-examination of C1-C5 alkyl nitrates in Hong Kong using an observation-based model

    Science.gov (United States)

    Lyu, X. P.; Ling, Z. H.; Guo, H.; Saunders, S. M.; Lam, S. H. M.; Wang, N.; Wang, Y.; Liu, M.; Wang, T.

    2015-11-01

    The photochemical formation of alkyl nitrates (RONO2) and their impact on ozone (O3) formation were investigated using a Photochemical Box Model incorporating the Master Chemical Mechanism (PBM-MCM). The model was constrained with field measurement data collected on selected O3 episode days at Tai O, a rural-coastal site in southwestern Hong Kong, from August 2001-December 2002. The in-situ observations showed that the sum of C1-C5 RONO2 varied from 30.7 ± 14.8 pptv in spring to 120.7 ± 10.4 pptv in autumn, of which 2-butyl nitrate dominated with the highest average concentration of 30.8 ± 2.6 pptv. Model simulations indicated that the pathway of CH3O reacting with NO2, proposed in our previous study, made minor contributions (11.3 ± 0.7%) to methyl nitrate formation. Indeed, 51.8 ± 3.1% and 36.5 ± 6.3% of the methyl nitrate was attributed to the reaction of CH3O2+NO and to oceanic emissions/biomass burning, respectively. For the C2-C5 alkyl nitrates, the contribution of photochemical formation increased with increasing carbon number, ranging from 64.4 ± 4.0% for ethyl nitrate (EtONO2) to 72.6 ± 4.2% for 2-pentyl nitrate (2-PenONO2), while the contribution of oceanic emissions/biomass burning decreased from 35.1 ± 6.5% for EtONO2 to 26.8 ± 6.8% for 2-PenONO2. Model simulations of photochemical O3 levels influenced by RONO2 chemistry showed that the formation of methyl-, ethyl-, i-propyl-, n-propyl-, 2-butyl-, 2-pentyl-, and 3-pentyl-nitrates led to O3 reduction of 0.05 ± 0.03, 0.05 ± 0.03, 0.06 ± 0.02, 0.02 ± 0.02, 0.18 ± 0.04, 0.09 ± 0.02 and 0.06 ± 0.02 ppbv, respectively, with an average reduction rate of 11.0 ± 3.2 ppbv O3 per 1 ppbv RONO2 formation. The C1-C5 RONO2 constituted 18.6 ± 1.9% of the entire RONO2, and had a nitrogen reserve of 4.1 ± 0.2%, implying their potential influence on O3 production in downwind areas.

  10. Characterization of a corrinoid protein involved in the C1 metabolism of strict anaerobic bacterium Moorella thermoacetica.

    Science.gov (United States)

    Das, Amaresh; Fu, Zheng-Qing; Tempel, Wolfram; Liu, Zhi-Jie; Chang, Jessie; Chen, Lirong; Lee, Doowon; Zhou, Weihong; Xu, Hao; Shaw, Neil; Rose, John P; Ljungdahl, Lars G; Wang, Bi-Cheng

    2007-04-01

    The strict anaerobic, thermophilic bacterium Moorella thermoacetica metabolizes C1 compounds for example CO(2)/H(2), CO, formate, and methanol into acetate via the Wood/Ljungdahl pathway. Some of the key steps in this pathway include the metabolism of the C1 compounds into the methyl group of methylenetetrahydrofolate (MTHF) and the transfer of the methyl group from MTHF to the methyl group of acetyl-CoA catalyzed by methyltransferase, corrinoid protein and CO dehydrogenase/acetyl CoA synthase. Recently, we reported the crystallization of a 25 kDa methanol-induced corrinoid protein from M. thermoacetica (Zhou et al., Acta Crystallogr F 2005; 61:537-540). In this study we analyzed the crystal structure of the 25 kDa protein and provide genetic and biochemical evidences supporting its role in the methanol metabolism of M. thermoacetia. The 25 kDa protein was encoded by orf1948 of contig 303 in the M. thermoacetica genome. It resembles similarity to MtaC the corrinoid protein of the methanol:CoM methyltransferase system of methane producing archaea. The latter enzyme system also contains two additional enzymes MtaA and MtaB. Homologs of MtaA and MtaB were found to be encoded by orf2632 of contig 303 and orf1949 of contig 309, respectively, in the M. thermoacetica genome. The orf1948 and orf1949 were co-transcribed from a single polycistronic operon. Metal analysis and spectroscopic data confirmed the presence of cobalt and the corrinoid in the purified 25 kDa protein. High resolution X-ray crystal structure of the purified 25 kDa protein revealed corrinoid as methylcobalamin with the imidazole of histidine as the alpha-axial ligand replacing benziimidazole, suggesting base-off configuration for the corrinoid. Methanol significantly activated the expression of the 25 kDa protein. Cyanide and nitrate inhibited methanol metabolism and suppressed the level of the 25 kDa protein. The results suggest a role of the 25 kDa protein in the methanol metabolism of M

  11. Measurements of C1-C4 alkyl nitrates and their relationships with carbonyl compounds and O3 in Chinese cities

    Science.gov (United States)

    Wang, Ming; Shao, Min; Chen, Wentai; Lu, Sihua; Wang, Chen; Huang, Daikuan; Yuan, Bin; Zeng, Limin; Zhao, Yue

    2013-12-01

    Ambient alkyl nitrates (RONO2) are important byproducts of O3 formation. Although concern about O3 pollution has increased recently, few studies have investigated RONO2 chemistry and distributions in China. In this study, ambient levels of C1-C4 RONO2 were measured in Chinese cities, and their relationships with parent hydrocarbons (RH), carbonyls, and total oxidant (Ox = O3 + NO2) were investigated. Our measurements showed that 2-butyl nitrate (2-BuONO2) was the most abundant RONO2 species, with mixing ratios of 48-88 pptv, followed by 2-propyl nitrate (2-PrONO2), ethyl nitrate (EtONO2), methyl nitrate (MeONO2), and 1-propyl nitrate (1-PrONO2). The measured RONO2 species exhibited maximum levels in the early afternoon (13:00-14:00) of summer, suggesting the importance of RONO2 photochemical production. Relative to 2-BuONO2/n-butane, the measured 1-PrONO2/propane agreed well with the modeled ratio based on laboratory kinetic data, suggesting that propane was the dominant precursor of ambient 1-PrONO2. However, the measured ratios for MeONO2/methane, EtONO2/ethane, and summertime 2-PrONO2/propane showed significant positive deviations from the predicted values, indicating the existence of additional sources other than OH oxidation of the parent hydrocarbons. Initial mixing ratios of C1-C3 carbonyls during 08:00-12:00 in summer at the PKU site exhibited significant correlations with RONO2 levels, suggesting the importance of secondary sources for ambient carbonyls. The measured ratios of formaldehyde/MeONO2 were close to the theoretical ratio, whereas the derived ratios for acetaldehyde/EtONO2, propanal/1-PrONO2, and acetone/2-PrONO2 were higher than the kinetic ratios, indicating that these carbonyls might be produced from sources other than the reaction of alkoxy radicals with O2. Carbonyls are important precursors of Ox, but their photochemical reactions do not result in RONO2 production. Therefore, Ox/RONO2 could indicate the relative importance of carbonyls to

  12. International consensus and practical guidelines on the gynecologic and obstetric management of female patients with hereditary angioedema caused by C1 inhibitor deficiency

    DEFF Research Database (Denmark)

    Caballero, Teresa; Farkas, Henriette; Bouillet, Laurence;

    2012-01-01

    section. Regional anesthesia is preferred to endotracheal intubation. Breast cancer: Attenuated androgens should be avoided. Antiestrogens can worsen angioedema symptoms. In these cases anastrozole might be an alternative. Other issues addressed include special features of HAE-C1-INH treatment in female...... patients, genetic counseling, infertility, abortion, lactation, menopause treatment, and endometrial cancer. CONCLUSIONS: A consensus for the management of female patients with HAE-C1-INH is presented....... devices, and progestins can be used. Pregnancy: Attenuated androgens are contraindicated and should be discontinued before attempting conception. Plasma-derived human C1 inhibitor concentrate (pdhC1INH) is preferred for acute treatment, short-term prophylaxis, or long-term prophylaxis. Tranexamic acid...

  13. 64 kDa protein is a candidate for a thyrotropin-releasing hormone receptor in prolactin-producing rat pituitary tumor cells (GH4C1 cells)

    International Nuclear Information System (INIS)

    A thyrotropin-releasing hormone (TRH) binding protein of 64 kDa has been identified by covalently crosslinking [3H]TRH to GH4C1 cells by ultraviolet illumination. The crosslinkage of [3H]TRH is UV-dose dependent and is inhibited by an excess of unlabeled TRH. A 64 kDa protein is also detected on immunoblots using an antiserum raised against GH4C1 cell surface epitopes. In a closely related cell line (GH12C1) which does not bind [3H]TRH, the 64 kDa protein cannot be demonstrated by [3H]TRH crosslinking nor by immunoblotting. These findings indicate that the 64 kDa protein is a candidate for a TRH-receptor protein in GH4C1 cells

  14. Promotion of cooperation in the form C0C1D classified by 'degree grads' in a scale-free network

    International Nuclear Information System (INIS)

    In this paper, we revisit the issue of the public goods game (PGG) on a heterogeneous graph. By introducing a new effective topology parameter, 'degree grads' ψ, we clearly classify the agents into three kinds, namely, C0, C1, and D. The mechanism for the heterogeneous topology promoting cooperation is discussed in detail from the perspective of C0C1D, which reflects the fact that the unreasoning imitation behaviour of C1 agents, who are 'cheated' by the well-paid C0 agents inhabiting special positions, stabilizes the formation of the cooperation community. The analytical and simulation results for certain parameters are found to coincide well with each other. The C0C1D case provides a picture of the actual behaviours in real society and thus is potentially of interest

  15. Expression patterns of semaphorin7A and plexinC1 during rat neural development suggest roles in axon guidance and neuronal migration

    Directory of Open Access Journals (Sweden)

    Hellemons Anita JCGM

    2007-08-01

    Full Text Available Abstract Background Although originally identified as embryonic axon guidance cues, semaphorins are now known to regulate multiple, distinct, processes crucial for neuronal network formation including axon growth and branching, dendritic morphology, and neuronal migration. Semaphorin7A (Sema7A, the only glycosylphosphatidylinositol-anchored semaphorin, promotes axon growth in vitro and is required for the proper growth of the mouse lateral olfactory tract in vivo. Sema7A has been postulated to signal through two unrelated receptors, an RGD-dependent α1β1-integrin and a member of the plexin family, plexinC1. β1-integrins underlie Sema7A-mediated axon growth and Sema7A function in the immune system. Sema7A-plexinC1 interactions have also been implicated in immune system function, but the neuronal role of this ligand-receptor pair remains to be explored. To gain further insight into the function(s of Sema7A and plexinC1 during neural development, we present here a detailed analysis of Sema7A and plexinC1 expression in the developing rat nervous system. Results In situ hybridization revealed select expression of Sema7A and plexinC1 in multiple neuronal systems including: the olfactory system, the hypothalamo-hypophysial system, the hippocampus, the meso-diencephalic dopamine system, and the spinal cord. Within these systems, Sema7A and plexinC1 are often expressed in specific neuronal subsets. In general, Sema7A transcript levels increase significantly towards adulthood, whereas plexinC1 expression decreases as development proceeds. PlexinC1, but not Sema7A, is strongly expressed by distinct populations of migrating neurons. In addition to neuronal expression, Sema7A and plexinC1 transcripts were detected in oligodendrocytes and ependymal cells, respectively. Conclusion Sema7A and plexinC1 expression patterns are consistent with these proteins serving both cooperative and separate functions during neural development. The prominent expression of

  16. Expression patterns of semaphorin7A and plexinC1 during rat neural development suggest roles in axon guidance and neuronal migration

    Science.gov (United States)

    Pasterkamp, R Jeroen; Kolk, Sharon M; Hellemons, Anita JCGM; Kolodkin, Alex L

    2007-01-01

    Background Although originally identified as embryonic axon guidance cues, semaphorins are now known to regulate multiple, distinct, processes crucial for neuronal network formation including axon growth and branching, dendritic morphology, and neuronal migration. Semaphorin7A (Sema7A), the only glycosylphosphatidylinositol-anchored semaphorin, promotes axon growth in vitro and is required for the proper growth of the mouse lateral olfactory tract in vivo. Sema7A has been postulated to signal through two unrelated receptors, an RGD-dependent α1β1-integrin and a member of the plexin family, plexinC1. β1-integrins underlie Sema7A-mediated axon growth and Sema7A function in the immune system. Sema7A-plexinC1 interactions have also been implicated in immune system function, but the neuronal role of this ligand-receptor pair remains to be explored. To gain further insight into the function(s) of Sema7A and plexinC1 during neural development, we present here a detailed analysis of Sema7A and plexinC1 expression in the developing rat nervous system. Results In situ hybridization revealed select expression of Sema7A and plexinC1 in multiple neuronal systems including: the olfactory system, the hypothalamo-hypophysial system, the hippocampus, the meso-diencephalic dopamine system, and the spinal cord. Within these systems, Sema7A and plexinC1 are often expressed in specific neuronal subsets. In general, Sema7A transcript levels increase significantly towards adulthood, whereas plexinC1 expression decreases as development proceeds. PlexinC1, but not Sema7A, is strongly expressed by distinct populations of migrating neurons. In addition to neuronal expression, Sema7A and plexinC1 transcripts were detected in oligodendrocytes and ependymal cells, respectively. Conclusion Sema7A and plexinC1 expression patterns are consistent with these proteins serving both cooperative and separate functions during neural development. The prominent expression of plexinC1 in several distinct

  17. Increased methylation of glucocorticoid receptor gene (NR3C1) in adults with a history of childhood maltreatment: a link with the severity and type of trauma

    OpenAIRE

    Perroud, N; Paoloni-Giacobino, A.; de Prada, P.; Olié, E; Salzmann, A; NICASTRO, R.; Guillaume, S.; Mouthon, D; Stouder, C; Dieben, K; Huguelet, P; Courtet, P; Malafosse, A.

    2011-01-01

    Childhood maltreatment, through epigenetic modification of the glucocorticoid receptor gene (NR3C1), influences the hypothalamic–pituitary–adrenal axis (HPA axis). We investigated whether childhood maltreatment and its severity were associated with increased methylation of the exon 1F NR3C1 promoter, in 101 borderline personality disorder (BPD) and 99 major depressive disorder (MDD) subjects with, respectively, a high and low rate of childhood maltreatment, and 15 MDD subjects with comorbid p...

  18. Mitochondrial Genome Sequencing in Mesolithic North East Europe Unearths a New Sub-Clade within the Broadly Distributed Human Haplogroup C1

    OpenAIRE

    Der Sarkissian, Clio; Brotherton, Paul; Balanovsky, Oleg; Templeton, Jennifer EL; Llamas, Bastien; Soubrier, Julien; Moiseyev, Vyacheslav; Khartanovich, Valery; Cooper, Alan; Haak, Wolfgang; The Genographic Consortium

    2014-01-01

    The human mitochondrial haplogroup C1 has a broad global distribution but is extremely rare in Europe today. Recent ancient DNA evidence has demonstrated its presence in European Mesolithic individuals. Three individuals from the 7,500 year old Mesolithic site of Yuzhnyy Oleni Ostrov, Western Russia, could be assigned to haplogroup C1 based on mitochondrial hypervariable region I sequences. However, hypervariable region I data alone could not provide enough resolution to establish the phyloge...

  19. Quantitative proteomic analysis of Niemann-Pick disease, type C1 cerebellum identifies protein biomarkers and provides pathological insight.

    Directory of Open Access Journals (Sweden)

    Stephanie M Cologna

    Full Text Available Niemann-Pick disease, type C1 (NPC1 is a fatal, neurodegenerative disorder for which there is no definitive therapy. In NPC1, a pathological cascade including neuroinflammation, oxidative stress and neuronal apoptosis likely contribute to the clinical phenotype. While the genetic cause of NPC1 is known, we sought to gain a further understanding into the pathophysiology by identifying differentially expressed proteins in Npc1 mutant mouse cerebella. Using two-dimensional gel electrophoresis and mass spectrometry, 77 differentially expressed proteins were identified in Npc1 mutant mice cerebella compared to controls. These include proteins involved in glucose metabolism, detoxification/oxidative stress and Alzheimer disease-related proteins. Furthermore, members of the fatty acid binding protein family, including FABP3, FABP5 and FABP7, were found to have altered expression in the Npc1 mutant cerebellum relative to control. Translating our findings from the murine model to patients, we confirm altered expression of glutathione s-transferase α, superoxide dismutase, and FABP3 in cerebrospinal fluid of NPC1 patients relative to pediatric controls. A subset of NPC1 patients on miglustat, a glycosphingolipid synthesis inhibitor, showed significantly decreased levels of FABP3 compared to patients not on miglustat therapy. This study provides an initial report of dysregulated proteins in NPC1 which will assist with further investigation of NPC1 pathology and facilitate implementation of therapeutic trials.

  20. Tissue localization of C1q in HBs antigen positive liver disease patients by direct immunofluorescent technique

    Directory of Open Access Journals (Sweden)

    Tsuji,Takao

    1977-02-01

    Full Text Available Tissue localization of a subcomponent of the first component of complement (CLq was examined in one postmortem case of HBs antigen (HBs Ag positive hepatocellular carcinoma and in six cases of chronic hepatitis from liver biopsy specimens. The direct immunofluorescent method was used after fixation with 2% para-formaldehyde in concentrated ammonium sulfate. CLq localization was found in collagen fibers and the cytoplasm of fibroblasts in the connective tissues of specimens examined. The localization was particularly marked in the region of the fundal glands of the gastric wall. Apart from collagen fibers, other sites of localization included the surface membrane of lymphocytes, especially those cells of the mesenteric lymph nodes. In HBs Ag positive specimens, immune deposit-like substances appeared localized intra-hepatically and in the renal glomeruli. Since C3 and C4 were identified concomitantly, it indicates that these substances were indeed immune diposits. Despite the finding that C3 and C4 were identified together in the hepatic cell cytoplasm, C1q itself was not demonstrated in all hepatic cell cytoplasms.