WorldWideScience

Sample records for 5a receptor chimeras

  1. Complement factor 5a receptor chimeras reveal the importance of lipid-facing residues in transport competence

    Klco, Jeffery M; Sen, Saurabh; Hansen, Jakob L;

    2009-01-01

    was exchanged with the cognate residues from the angiotensin type 1 receptor. Disulfide-trapping and bioluminescence resonance energy transfer (BRET) studies demonstrated robust homodimerization of both complement factor 5a receptor and angiotensin type 1 receptor, but no evidence for heterodimerization...

  2. Analysis of the hormone-binding domain of steroid receptors using chimeras generated by homologous recombination

    The glucocorticoid receptor and the mineralocorticoid receptor are members of the steroid receptor family that exhibit ligand cross-reactivity. Specificity of steroid receptor action is investigated in the present work by the construction and characterization of chimeras between the glucocorticoid receptor and the mineralocorticoid receptor. We used an innovative approach to make novel steroid receptor proteins in vivo that in general, contrary to our expectations, show increased ligand specificity compared to the parental receptors. We describe a receptor that is specific for the potent synthetic glucocorticoid triamcinolone acetonide and does not bind aldosterone. A further set of chimeras has an increased ability to discriminate between ligands, responding potently to mineralocorticoids and only very weakly to synthetic glucocorticoids. A chimera with the fusion site in the hinge highlights the importance of the region between the DNA-binding and the hormone-binding domains since, unlike both the glucocorticoid and mineralocorticoid receptors, it only responds to mineralocorticoids. One chimera has reduced specificity in that it acts as a general corticoid receptor, responding to glucocorticoids and mineralocorticoids with similar potency and efficacy. Our data suggest that regions of the glucocorticoid and mineralocorticoid receptor hormone-binding domains are functionally non-reciprocal. We present transcriptional, hormone-binding, and structure-modeling evidence that suggests that receptor-specific interactions within and across domains mediate aspects of specificity in transcriptional responses to steroids

  3. Allosteric and orthosteric sites in CC chemokine receptor (CCR5), a chimeric receptor approach

    Thiele, Stefanie; Steen, Anne; Jensen, Pia C;

    2011-01-01

    -allosteric molecules. A chimera was successfully constructed between CCR5 and the closely related CCR2 by transferring all extracellular regions of CCR2 to CCR5, i.e. a Trojan horse that resembles CCR2 extracellularly but signals through a CCR5 transmembrane unit. The chimera bound CCR2 (CCL2 and CCL7), but not CCR5...... preserved, the allosteric enhancement of chemokine binding was disrupted. In summary, the Trojan horse chimera revealed that orthosteric and allosteric sites could be structurally separated and still act together with transmission of agonism and antagonism across the different receptor units....

  4. Controlling chimeras

    Bick, Christian; Martens, Erik Andreas

    2015-01-01

    Coupled phase oscillators model a variety of dynamical phenomena in nature and technological applications. Non-local coupling gives rise to chimera states which are characterized by a distinct part of phase-synchronized oscillators while the remaining ones move incoherently. Here, we apply the idea of control to chimera states: using gradient dynamics to exploit drift of a chimera, it will attain any desired target position. Through control, chimera states become functionally relevant; for ex...

  5. Fatty acids activate a chimera of the clofibric acid-activated receptor and the glucocorticoid receptor.

    Göttlicher, M; Widmark, E; Q. Li; Gustafsson, J.A.

    1992-01-01

    Peroxisome proliferators such as clofibric acid, nafenopin, and WY-14,643 have been shown to activate PPAR (peroxisome proliferator-activated receptor), a member of the steroid nuclear receptor superfamily. We have cloned the cDNA from the rat that is homologous to that from the mouse [Issemann, I. & Green, S. (1990) Nature (London) 347, 645-650], which encodes a 97% similar protein with a particularly well-conserved putative ligand-binding domain. To search for physiologically occurring acti...

  6. Controlling chimeras

    Bick, Christian; Martens, Erik A.

    2015-03-01

    Coupled phase oscillators model a variety of dynamical phenomena in nature and technological applications. Non-local coupling gives rise to chimera states which are characterized by a distinct part of phase-synchronized oscillators while the remaining ones move incoherently. Here, we apply the idea of control to chimera states: using gradient dynamics to exploit drift of a chimera, it will attain any desired target position. Through control, chimera states become functionally relevant; for example, the controlled position of localized synchrony may encode information and perform computations. Since functional aspects are crucial in (neuro-)biology and technology, the localized synchronization of a chimera state becomes accessible to develop novel applications. Based on gradient dynamics, our control strategy applies to any suitable observable and can be generalized to arbitrary dimensions. Thus, the applicability of chimera control goes beyond chimera states in non-locally coupled systems.

  7. Characterization of the isolated granulocyte C5a receptor

    The authors previously demonstrated that the C5a receptor may be covalently labeled with a photoreactive C5a analog termed AMEA-SC5a. The resulting C5a-receptor complex exhibits a molecular weight of 52,000 Daltons on SDS-PAGE. More recently, they have been able to characterize the C5a receptor itself, rather than the C5a-receptor complex. This was achieved by specifically radioiodinating the granulocyte C5a receptor with a unique C5a photoaffinity probe (ASAMEA-SC5a) that contained on 125I-labeled p-azido-salicylate moiety. After this probe was bound to the membrane receptor and the resulting complex was photolyzed, the C5a polypeptide was released by reductive cleavage with DTT. The resulting radiolabeled receptor was then separated from free C5a and analyzed by SDS-PAGE under reducing conditions. The C5a receptor was identified as a single molecular species with an apparent molecular weight of 46,000 to 47,000 Daltons. Furthermore, addition of disuccinimidyl suberate (DSS) to preformed C5a receptor complexes resulted in relatively selective crosslinking of the C5a receptor to a second protein with an apparent molecular weight of ca. 40,000 Daltons. These findings suggest that the C5a receptor to a second protein with an apparent molecular weight of ca. 40,000 Daltons. These findings suggest that C5a receptor may consist of two functionally different subunits or it is in close proximity to other unique membrane constituents

  8. Pharmacological characterisation of α6β4* nicotinic acetylcholine receptors assembled from three different α6/α3 subunit chimeras in tsA201 cells

    Jensen, Anne Bjørnskov; Hoestgaard-Jensen, Kirsten; Jensen, Anders A.

    2014-01-01

    on these results should be made keeping the molecular modifications in the α6 surrogate subunits in mind, this study sheds light on the pharmacological properties of α6β4⁎ nicotinic acetylcholine receptors and demonstrates the applicability of the C6F223L and C16F223L chimeras for studies of these...

  9. Controlling Chimeras

    Martens, Erik Andreas; Bick, Christian

    2015-01-01

    Coupled phase oscillators model a variety of dynamical phenomena in nature and technological applications. Non-local coupling gives rise to chimera states which are characterized by a distinct part of phase-synchronized oscillators while the remaining ones move incoherently. Here, we apply the idea...... of control to chimera states: using gradient dynamics to exploit drift of a chimera, it will attain any desired target position. Through control, chimera states become functionally relevant; for example, the controlled position of localized synchrony may encode information and perform computations....... Since functional aspects are crucial in (neuro-)biology and technology, the localized synchronization of a chimera state becomes accessible to develop novel applications. Based on gradient dynamics, our control strategy applies to any suitable observable and can be generalized to arbitrary dimensions...

  10. Bridge Technology with TSH Receptor Chimera for Sensitive Direct Detection of TSH Receptor Antibodies Causing Graves' Disease: Analytical and Clinical Evaluation.

    Frank, C U; Braeth, S; Dietrich, J W; Wanjura, D; Loos, U

    2015-11-01

    Graves' disease is caused by stimulating autoantibodies against the thyrotropin receptor inducing uncontrolled overproduction of thyroid hormones. A Bridge Assay is presented for direct detection of these thyroid-stimulating immunoglobulins using thyrotropin receptor chimeras. A capture receptor, formed by replacing aa residues 261-370 of the human thyrotropin receptor with residues 261-329 from rat lutropin/choriogonadotropin receptor and fixed to microtiter plates, binds one arm of the autoantibody. The second arm bridges to the signal receptor constructed from thyrotropin receptor (aa 21-261) and secretory alkaline phosphatase (aa 1-519) inducing chemiluminescence. The working range of the assay is from 0.3 IU/l to 50 IU/l with a cutoff of 0.54 IU/l and functional sensitivity of 0.3 IU/l. Sensitivity and specificity are 99.8 and 99.1%, respectively, with a diagnostic accuracy of 0.998. The low grey zone is from 0.3-0.54 IU/l. The stimulatory character of the assayed antibodies is shown through a good correlation (r=0.7079, preceptor competition assay and in the blocking bioassay, antibodies are not detected by the Bridge Assay, while the monoclonal blocking antibody K1-70 was detected. In Hashimoto disease thyrotropin receptor autoantibodies are detected in some patients, but not in goiter. This Bridge Assay delivers good diagnostic accuracy for identification of Graves' disease patients. Its high sensitivity may facilitate early detection of onset, remission, or recurrence of Graves' disease enabling timely adaption of the treatment.Human genes: TSHR, Homo sapiens, acc. no. M31774.1. PMID:26079838

  11. Thyrotropin-luteinizing hormone/chorionic gonadotropin receptor extracellular domain chimeras as probes for thyrotropin receptor function.

    Nagayama, Y; Wadsworth, H L; Chazenbalk, G D; Russo, D.; Seto, P; Rapoport, B

    1991-01-01

    To define the sites in the extracellular domain of the human thyrotropin (TSH) receptor that are involved in TSH binding and signal transduction we constructed chimeric thyrotropin-luteinizing hormone/chorionic gonadotropin (TSH-LH/CG) receptors. The extracellular domain of the human TSH receptor was divided into five regions that were replaced, either singly or in various combinations, with homologous regions of the rat LH/CG receptor. The chimeric receptors were stably expressed in Chinese ...

  12. A C-terminal segment of the V1R vasopressin receptor is unstructured in the crystal structure of its chimera with the maltose-binding protein

    The 1.8 Å crystal structure of an MBP-fusion protein with the C-terminal cytoplasmic segment of the V1 vasopressin receptor reveals that the receptor segment is unstructured. The V1 vascular vasopressin receptor (V1R) is a G-protein-coupled receptor (GPCR) involved in the regulation of body-fluid osmolality, blood volume and blood pressure. Signal transduction is mediated by the third intracellular loop of this seven-transmembrane protein as well as by the C-terminal cytoplasmic segment. A chimera of the maltose-binding protein (MBP) and the C-terminal segment of V1R has been cloned, expressed, purified and crystallized. The crystals belong to space group P21, with unit-cell parameters a = 51.10, b = 66.56, c = 115.72 Å, β = 95.99°. The 1.8 Å crystal structure reveals the conformation of MBP and part of the linker region of this chimera, with the C-terminal segment being unstructured. This may reflect a conformational plasticity in the C-terminal segment that may be necessary for proper function of V1R

  13. Inter-species chimeras of leukaemia inhibitory factor define a major human receptor-binding determinant.

    Owczarek, C M; Layton, M. J.; Metcalf, D; Lock, P; Willson, T A; Gough, N M; Nicola, N A

    1993-01-01

    Human leukaemia inhibitory factor (hLIF) binds to both human and mouse LIF receptors (LIF-R), while mouse LIF (mLIF) binds only to mouse LIF-R. Moreover, hLIF binds with higher affinity to the mLIF-R than does mLIF. In order to define the regions of the hLIF molecule responsible for species-specific interaction with the hLIF-R and for the unusual high-affinity binding to the mLIF-R, a series of 15 mouse/human LIF hybrids has been generated. Perhaps surprisingly, both of these properties mappe...

  14. Novel GLP-1 fusion chimera as potent long acting GLP-1 receptor agonist.

    Qinghua Wang

    Full Text Available GLP-1 has a variety of anti-diabetic effects. However, native GLP-1 is not suitable for therapy of diabetes due to its short half-life (t1/2168 h. Intraperitoneal glucose tolerance test (IPGTT in mice showed that GLP-1/hIgG2 significantly decreased glucose excursion. Furthermore, IPGTT performed on mice one week after a single drug-injection also displayed significantly reduced glucose excursion, indicating that GLP-1/hIgG2 fusion protein has long-lasting effects on the modulation of glucose homeostasis. GLP-1/hIgG2 was found to be effective in reducing the incidence of diabetes in multiple-low-dose streptozotocin-induced type 1 diabetes in mice. Together, the long-lasting bioactive GLP-1/hIgG2 retains native GLP-1 activities and thus may serve as a potent GLP-1 receptor agonist.

  15. Allosterism in human complement component 5a ((h)C5a): a damper of C5a receptor (C5aR) signaling.

    Rana, Soumendra; Sahoo, Amita Rani; Majhi, Bharat Kumar

    2016-06-01

    The phenomena of allosterism continues to advance the field of drug discovery, by illuminating gainful insights for many key processes, related to the structure-function relationships in proteins and enzymes, including the transmembrane G-protein coupled receptors (GPCRs), both in normal as well as in the disease states. However, allosterism is completely unexplored in the native protein ligands, especially when a small covalent change significantly modulates the pharmacology of the protein ligands toward the signaling axes of the GPCRs. One such example is the human C5a ((h)C5a), the potent cationic anaphylatoxin that engages C5aR and C5L2 to elicit numerous immunological and non-immunological responses in humans. From the recently available structure-function data, it is clear that unlike the mouse C5a ((m)C5a), the (h)C5a displays conformational heterogeneity. However, the molecular basis of such conformational heterogeneity, otherwise allosterism in (h)C5a and its precise contribution toward the overall C5aR signaling is not known. This study attempts to decipher the functional role of allosterism in (h)C5a, by exploring the inherent conformational dynamics in (m)C5a, (h)C5a and in its point mutants, including the proteolytic mutant des-Arg(74)-(h)C5a. Prima facie, the comparative molecular dynamics study, over total 500 ns, identifies Arg(74)-Tyr(23) and Arg(37)-Phe(51) "cation-π" pairs as the molecular "allosteric switches" on (h)C5a that potentially functions as a damper of C5aR signaling. PMID:26212097

  16. Self-propelled Chimeras

    Kruk, Nikita; Maistrenko, Yuri; Wenzel, Nicolas; Koeppl, Heinz

    2015-01-01

    We report the appearance of chimera states in a minimal extension of the classical Vicsek model for collective motion of self-propelled particle systems. Inspired by earlier works on chimera states in the Kuramoto model, we introduce a phase lag parameter in the particle alignment dynamics. Compared to the oscillatory networks with fixed site positions, the self-propelled particle systems can give rise to distinct forms of chimeras resembling moving flocks through an incoherent surrounding, f...

  17. Amplitude mediated chimera states

    Sethia, Gautam C.; Sen, Abhijit; Johnston, George L.

    2013-01-01

    We investigate the possibility of obtaining chimera state solutions of the non-local Complex Ginzburg-Landau Equation (NLCGLE) in the strong coupling limit when it is important to retain amplitude variations. Our numerical studies reveal the existence of a variety of amplitude mediated chimera states (including stationary and non-stationary two cluster chimera states), that display intermittent emergence and decay of amplitude dips in their phase incoherent regions. The existence regions of t...

  18. Quantum chimera states

    Viennot, David; Aubourg, Lucile

    2016-02-01

    We study a theoretical model of closed quasi-hermitian chain of spins which exhibits quantum analogues of chimera states, i.e. long life classical states for which a part of an oscillator chain presents an ordered dynamics whereas another part presents a disordered dynamics. For the quantum analogue, the chimera behaviour deals with the entanglement between the spins of the chain. We discuss the entanglement properties, quantum chaos, quantum disorder and semi-classical similarity of our quantum chimera system. The quantum chimera concept is novel and induces new perspectives concerning the entanglement of multipartite systems.

  19. Gargoyles, Grotesques, & Chimeras

    Wilbert, Nancy Corrigan

    2010-01-01

    Gargoyles, grotesques, and chimeras are scary, mythical (and sometimes humorous) creatures that have functional, decorative, and spiritual significance in medieval architecture. In this article, the author describes how her ceramics students created contemporary versions of gargoyles, chimeras, and grotesque faces. (Contains 1 online resource.)

  20. Chimera states in bursting neurons

    Bera, Bidesh K.; Ghosh, Dibakar; Lakshmanan, M.

    2015-01-01

    We study the existence of chimera states in pulse-coupled networks of bursting Hindmarsh-Rose neurons with nonlocal, global and local (nearest neighbor) couplings. Through a linear stability analysis, we discuss the behavior of stability function in the incoherent (i.e. disorder), coherent, chimera and multi-chimera states. Surprisingly, we find that chimera and multi-chimera states occur even using local nearest neighbor interaction in a network of identical bursting neurons alone. This is i...

  1. A C-terminal segment of the V{sub 1}R vasopressin receptor is unstructured in the crystal structure of its chimera with the maltose-binding protein

    Adikesavan, Nallini Vijayarangan; Mahmood, Syed Saad; Stanley, Nithianantham; Xu, Zhen; Wu, Nan [Department of Biochemistry, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-4935 (United States); Thibonnier, Marc [Department of Medicine, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-4935 (United States); Shoham, Menachem, E-mail: mxs10@case.edu [Department of Biochemistry, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-4935 (United States)

    2005-04-01

    The 1.8 Å crystal structure of an MBP-fusion protein with the C-terminal cytoplasmic segment of the V1 vasopressin receptor reveals that the receptor segment is unstructured. The V{sub 1} vascular vasopressin receptor (V{sub 1}R) is a G-protein-coupled receptor (GPCR) involved in the regulation of body-fluid osmolality, blood volume and blood pressure. Signal transduction is mediated by the third intracellular loop of this seven-transmembrane protein as well as by the C-terminal cytoplasmic segment. A chimera of the maltose-binding protein (MBP) and the C-terminal segment of V{sub 1}R has been cloned, expressed, purified and crystallized. The crystals belong to space group P2{sub 1}, with unit-cell parameters a = 51.10, b = 66.56, c = 115.72 Å, β = 95.99°. The 1.8 Å crystal structure reveals the conformation of MBP and part of the linker region of this chimera, with the C-terminal segment being unstructured. This may reflect a conformational plasticity in the C-terminal segment that may be necessary for proper function of V{sub 1}R.

  2. Labeling the granulocyte C5a receptor with a unique photoreactive probe

    Human C5a anaphylatoxin is a complement-derived chemotactic factor that binds to specific receptors that are found in the granulocyte plasma membrane. These receptors, or a specific subunit of these receptors, can be covalently labeled with a unique photoreactive analog of human C5a. This photoaffinity probe, p-azidobenzoyl-2-mercapto-N-ethylamide-C5a (ABMEA-SC5a), was synthesized by coupling p-azidobenzoyl-2-mercapto-N-ethylamide-2'-thiopyridine disulfide to human C5a after it had been partially reduced with dithiothreitol. Both direct and competitive binding studies demonstrated that a radioiodinated ABMEA-SC5a derivative retained the capacity to specifically bind to either neutrophil or U937 cell C5a receptors. Half-maximal binding of the photoreactive analog was observed at a concentration of 1 to 2 nM, a value that is comparable to that observed when 125I-C5a is employed as the ligand. The covalent adducts that were formed after irradiation of 125I-ABMEA-SC5a that had been prebound to either neutrophil or U937 cell plasma membranes were found to have an apparent molecular mass of 52,000 daltons when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis techniques. These findings demonstrate that the C5a receptors found on human neutrophils and other granulocytes are not only functionally similar, but biochemically similar as well

  3. Quantum chimera states

    Viennot, David; Aubourg, Lucile

    2014-01-01

    We study a theoretical model of closed quasi-hermitian chain of spins which exhibits quantum analogues of chimera states, i.e. long life classical states for which a part of an oscillator chain presents an ordered dynamics whereas another part presents a disordered chaotic dynamics. For the quantum analogue, the chimera behavior deals with the entanglement between the spins of the chain. We discuss the entanglement properties, quantum chaos, quantum disorder and semi-classical similarity of o...

  4. Signaling through C5a receptor and C3a receptor diminishes function of murine natural regulatory T cells

    Kwan, Wing-hong; Van der Touw, William; Paz-Artal, Estela; Li, Ming O.; Heeger, Peter S.

    2013-01-01

    Thymus-derived (natural) CD4+ FoxP3+ regulatory T cells (nT reg cells) are required for immune homeostasis and self-tolerance, but must be stringently controlled to permit expansion of protective immunity. Previous findings linking signals transmitted through T cell–expressed C5a receptor (C5aR) and C3a receptor (C3aR) to activation, differentiation, and expansion of conventional CD4+CD25− T cells (T conv cells), raised the possibility that C3aR/C5aR signaling on nT reg cells could physiologi...

  5. Chimeras of receptors for gibbon ape leukemia virus/feline leukemia virus B and amphotropic murine leukemia virus reveal different modes of receptor recognition by retrovirus

    Pedersen, Lene; Johann, Stephen V; van Zeijl, Marja;

    1995-01-01

    Glvr1 encodes the human receptor for gibbon ape leukemia virus (GALV) and feline leukemia virus subgroup B (FeLV-B), while the related gene Glvr2 encodes the human receptor for amphotropic murine leukemia viruses (A-MLVs). The two proteins are 62% identical in their amino acid sequences and are...

  6. Differentiation and functional maturation of bone marrow-derived intestinal epithelial T cells expressing membrane T cell receptor in athymic radiation chimeras

    The thymus dependency of murine intestinal intraepithelial lymphocytes (IEL) was studied in an athymic F1----parent radiation chimera model. IEL, although not splenic or lymph node lymphocytes, from athymic chimeras displayed normal levels of cells bearing the class-specific T cell Ag, CD4 and CD8; the TCR-associated molecule, CD3; and the Thy-1 Ag. Moreover, two-color flow cytometric analyses of IEL from athymic mice demonstrated regulated expression of T cell Ag characteristic of IEL subset populations from thymus-bearing mice. In immunoprecipitation experiments, surface TCR-alpha beta or TCR-gamma delta were expressed on IEL, although not on splenic lymphocytes, from athymic chimeras. That IEL from athymic chimeras constituted a population of functionally mature effector cells activated in situ, similar to IEL from thymus-bearing mice, was demonstrated by the presence of CD3-mediated lytic activity of athymic lethally irradiated bone marrow reconstituted IEL. These data provide compelling evidence that intestinal T cells do not require thymic influence for maturation and development, and demonstrate that the microenvironment of the intestinal epithelium is uniquely adapted to regulate IEL differentiation

  7. Amplitude chimeras and chimera death in dynamical networks

    Zakharova, Anna; Kapeller, Marie; Schöll, Eckehard

    2016-06-01

    We find chimera states with respect to amplitude dynamics in a network of Stuart- Landau oscillators. These partially coherent and partially incoherent spatio-temporal patterns appear due to the interplay of nonlocal network topology and symmetry-breaking coupling. As the coupling range is increased, the oscillations are quenched, amplitude chimeras disappear and the network enters a symmetry-breaking stationary state. This particular regime is a novel pattern which we call chimera death. It is characterized by the coexistence of spatially coherent and incoherent inhomogeneous steady states and therefore combines the features of chimera state and oscillation death. Additionally, we show two different transition scenarios from amplitude chimera to chimera death. Moreover, for amplitude chimeras we uncover the mechanism of transition towards in-phase synchronized regime and discuss the role of initial conditions.

  8. Sulfated Tyrosines Contribute to the Formation of the C5a Docking Site of the Human C5a Anaphylatoxin Receptor

    Farzan, Michael; Schnitzler, Christine E.; Vasilieva, Natalya; Leung, Doris; Kuhn, Jens; Gerard, Craig; Gerard, Norma P.; Choe, Hyeryun

    2001-01-01

    The complement anaphylatoxin C5a and its seven-transmembrane segment (7TMS) receptor play an important role in host defense and in a number of inflammation-associated pathologies. The NH2-terminal domain of the C5a receptor (C5aR/CD88) contributes substantially to its ability to bind C5a. Here we show that the tyrosines at positions 11 and 14 of the C5aR are posttranslationally modified by the addition of sulfate groups. The sulfate moieties of each of these tyrosines are critical to the ability of the C5aR to bind C5a and to mobilize calcium. A C5aR variant lacking these sulfate moieties efficiently mobilized calcium in response to a small peptide agonist, but not to C5a, consistent with a two-site model of ligand association in which the tyrosine-sulfated region of the C5aR mediates the initial docking interaction. A peptide based on the NH2 terminus of the C5aR and sulfated at these two tyrosines, but not its unsulfated analogue or a doubly sulfated control peptide, partially inhibited C5a association with its receptor. These observations clarify structural and mutagenic studies of the C5a/C5aR association and suggest that related 7TMS receptors are also modified by functionally important sulfate groups on their NH2-terminal tyrosines. PMID:11342590

  9. Reduced expression of C5a receptors on neutrophils from cord blood

    Nybo, Mads; Sørensen, O; Leslie, R; Wang, P

    1998-01-01

    AIM: To describe further functional deficiencies of neonatal neutrophils by measuring the expression of C5a receptors. METHODS: C5a uptake was measured using flow cytometry with fluorescein isothiocynate labelled recombinant C5a. The response of neutrophils to stimulation with C5a and fMLP was...... tested by measuring migration and exocytosis of myeloperoxidase and lactoferrin. RESULTS: C5a mean fluorescence on neutrophils from neonates was significantly lower (22.4 (SD 3.5)) than in adult controls (31.5 (3.1)). Neutrophils from neonates migrated poorly towards both C5a and fMLP compared with those...... from adult controls. Exocytosis of myeloperoxidase, but not lactoferrin from neonatal neutrophils stimulated with C5a, was significantly lower than in adult controls. fMLP stimulation, on the other hand, resulted in significantly higher exocytosis in neonates. CONCLUSION: The lower expression of C5a...

  10. Quantum signatures of chimera states

    Bastidas, V. M.; Omelchenko, I.; Zakharova, A.; Schöll, E.; Brandes, T.

    2015-12-01

    Chimera states are complex spatiotemporal patterns in networks of identical oscillators, characterized by the coexistence of synchronized and desynchronized dynamics. Here we propose to extend the phenomenon of chimera states to the quantum regime, and uncover intriguing quantum signatures of these states. We calculate the quantum fluctuations about semiclassical trajectories and demonstrate that chimera states in the quantum regime can be characterized by bosonic squeezing, weighted quantum correlations, and measures of mutual information. Our findings reveal the relation of chimera states to quantum information theory, and give promising directions for experimental realization of chimera states in quantum systems.

  11. Urokinase Receptor Mediates Osteogenic Differentiation of Mesenchymal Stem Cells and Vascular Calcification via the Complement C5a Receptor

    Anaraki, Parnian Kalbasi; Patecki, Margret; Larmann, Jan; Tkachuk, Sergey; Jurk, Kerstin; Haller, Hermann; Theilmeier, Gregor; Dumler, Inna

    2013-01-01

    Vascular calcification is a severe consequence of several pathological processes with a lack of effective therapy. Recent studies suggest that circulating and resident mesenchymal stem cells (MSC) contribute to the osteogenic program of vascular calcification. Molecular mechanisms underlying MSC osteogenic potential and differentiation remain, however, sparsely explored. We investigated a role for the complement receptor C5aR in these processes. We found that expression of C5aR was upregulate...

  12. Chimera: Experiencing Language Arts.

    Paul, Rebecca K.

    1991-01-01

    Describes the production of a dramatic musical, Chimera: A Journey to Redoubtia, at Chapman Elementary School in Anchor Point, Alaska. Student participation in the project, and students' rewards from participation, are detailed. Benefits of the integration of dramatics into the language arts curriculum are listed. (BB)

  13. Chimera and globally clustered chimera: Impact of time delay

    Sheeba, Jane H.; Chandrasekar, V. K.; Lakshmanan, M.

    2010-01-01

    Following a short report of our preliminary results [Phys. Rev. E 79, 055203(R) (2009)], we present a more detailed study of the effects of coupling delay in diffusively coupled phase oscillator populations. We find that coupling delay induces chimera and globally clustered chimera (GCC) states in delay coupled populations. We show the existence of multi-clustered states that act as link between the chimera and the GCC states. A stable GCC state goes through a variety of GCC states, namely pe...

  14. Amplitude chimeras and chimera death in dynamical networks

    Zakharova, Anna; Kapeller, Marie; Schöll, Eckehard

    2015-01-01

    We find chimera states with respect to amplitude dynamics in a network of Stuart-Landau oscillators. These partially coherent and partially incoherent spatio-temporal patterns appear due to the interplay of nonlocal network topology and symmetry-breaking coupling. As the coupling range is increased, the oscillations are quenched, amplitude chimeras disappear and the network enters a symmetry-breaking stationary state. This particular regime is a novel pattern which we call chimera death. It i...

  15. Chimera states in bursting neurons

    Bera, Bidesh K.; Ghosh, Dibakar; Lakshmanan, M.

    2016-01-01

    We study the existence of chimera states in pulse-coupled networks of bursting Hindmarsh-Rose neurons with nonlocal, global, and local (nearest neighbor) couplings. Through a linear stability analysis, we discuss the behavior of the stability function in the incoherent (i.e., disorder), coherent, chimera, and multichimera states. Surprisingly, we find that chimera and multichimera states occur even using local nearest neighbor interaction in a network of identical bursting neurons alone. This is in contrast with the existence of chimera states in populations of nonlocally or globally coupled oscillators. A chemical synaptic coupling function is used which plays a key role in the emergence of chimera states in bursting neurons. The existence of chimera, multichimera, coherent, and disordered states is confirmed by means of the recently introduced statistical measures and mean phase velocity.

  16. Cellular automaton for chimera states

    García-Morales, Vladimir

    2016-01-01

    A minimalistic model for chimera states is presented. The model is a cellular automaton (CA) which depends on only one adjustable parameter, the range of the nonlocal coupling, and is built from elementary cellular automata and the majority (voting) rule. This suggests the universality of chimera-like behavior from a new point of view: Already simple CA rules based on the majority rule exhibit this behavior. After a short transient, we find chimera states for arbitrary initial conditions, the...

  17. Quantum signatures of Chimera states

    Bastidas, V. M.; Omelchenko, I.; ZAKHAROVA, A.; Schöll, E.; Brandes, T.

    2015-01-01

    Chimera states are complex spatiotemporal patterns in networks of identical oscillators, characterized by the coexistence of synchronized and desynchronized dynamics. Here we propose to extend the phenomenon of chimera states to the quantum regime, and uncover intriguing quantum signatures of these states. We calculate the quantum fluctuations about semiclassical trajectories and demonstrate that chimera states in the quantum regime can be characterized by bosonic squeezing, weighted quantum ...

  18. Chimera Grid Tools

    Chan, William M.; Rogers, Stuart E.; Nash, Steven M.; Buning, Pieter G.; Meakin, Robert

    2005-01-01

    Chimera Grid Tools (CGT) is a software package for performing computational fluid dynamics (CFD) analysis utilizing the Chimera-overset-grid method. For modeling flows with viscosity about geometrically complex bodies in relative motion, the Chimera-overset-grid method is among the most computationally cost-effective methods for obtaining accurate aerodynamic results. CGT contains a large collection of tools for generating overset grids, preparing inputs for computer programs that solve equations of flow on the grids, and post-processing of flow-solution data. The tools in CGT include grid editing tools, surface-grid-generation tools, volume-grid-generation tools, utility scripts, configuration scripts, and tools for post-processing (including generation of animated images of flows and calculating forces and moments exerted on affected bodies). One of the tools, denoted OVERGRID, is a graphical user interface (GUI) that serves to visualize the grids and flow solutions and provides central access to many other tools. The GUI facilitates the generation of grids for a new flow-field configuration. Scripts that follow the grid generation process can then be constructed to mostly automate grid generation for similar configurations. CGT is designed for use in conjunction with a computer-aided-design program that provides the geometry description of the bodies, and a flow-solver program.

  19. C5a receptor deficiency alters energy utilization and fat storage.

    Christian Roy

    Full Text Available OBJECTIVE: To investigate the impact of whole body C5a receptor (C5aR deficiency on energy metabolism and fat storage. DESIGN: Male wildtype (WT and C5aR knockout (C5aRKO mice were fed a low fat (CHOW or a high fat high sucrose diet-induced obesity (DIO diet for 14 weeks. Body weight and food intake were measured weekly. Indirect calorimetry, dietary fatload clearance, insulin and glucose tolerance tests were also evaluated. Liver, muscle and adipose tissue mRNA gene expression were measured by RT-PCR. RESULTS: At week one and 12, C5aRKO mice on DIO had increased oxygen consumption. After 12 weeks, although food intake was comparable, C5aRKO mice had lower body weight (-7% CHOW, -12% DIO as well as smaller gonadal (-38% CHOW, -36% DIO and inguinal (-29% CHOW, -30% DIO fat pads than their WT counterparts. Conversely, in WT mice, C5aR was upregulated in DIO vs CHOW diets in gonadal adipose tissue, muscle and liver, while C5L2 mRNA expression was lower in C5aRKO on both diet. Furthermore, blood analysis showed lower plasma triglyceride and non-esterified fatty acid levels in both C5aRKO groups, with faster postprandial triglyceride clearance after a fatload. Additionally, C5aRKO mice showed lower CD36 expression in gonadal and muscle on both diets, while DGAT1 expression was higher in gonadal (CHOW and liver (CHOW and DIO and PPARγ was increased in muscle and liver. CONCLUSION: These observations point towards a role (either direct or indirect for C5aR in energy expenditure and fat storage, suggesting a dual role for C5aR in metabolism as well as in immunity.

  20. Increased expression of C5a receptor (CD88) mRNA in canine mammary tumors.

    Hezmee, Mohd Noor Mohd; Kyaw-Tanner, Myat; Lee, Jia Yu Peppermint; Shiels, Ian A; Rolfe, Barbara; Woodruff, Trent; Mills, Paul C

    2011-01-01

    Mammary tumors are among the most common neoplastic conditions in dogs, and there is evidence that inflammation plays a role in the development of some tumor types in dogs. The complement system is a major participant in the inflammatory process and the complement activation component, C5a, is a potent inflammatory peptide. This study investigated the mRNA expression of the major receptor for C5a (C5aR; CD88) in histopathological samples of canine mammary tumors by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) using canine-specific primers for CD88. A total of seven canine mammary tumors (four malignant carcinomas, two benign mixed mammary tumors, and one myoepithelioma) and eight normal mammary glands were analysed. All the tumor samples expressed low levels of CD88 mRNA, while none of the normal mammary tissues showed any detectable expression. These preliminary results suggest that C5a-CD88 interaction may play a contributory role in the inflammatory response associated with mammary tumor development in dogs. Further studies investigating the mechanisms behind complement activation and C5a receptor expression in canine mammary tumors are warranted. PMID:20846729

  1. Functional coupling of a recombinant Human 5-HT5A receptor to G-proteins in HEK-293 cells

    Hurley, P T; McMahon, R. A.; Fanning, P; O'Boyle, K M; Rogers, M; Martin, F

    1998-01-01

    We have cloned, expressed and pharmacologically characterized the Human 5-HT5A receptor.We have shown that ligand activation of the Human 5-HT5A receptor results in functional coupling to G-proteins in HEK-293 cells.Stimulation of the receptor with 5-CT (5-carboxamidotryptamine) resulted in a dose-dependent increase in the % [35S]-GTPγS binding over the basal level. This is the first study to describe such G-protein activation for the Human 5-HT5A receptor in any cell.A dose-dependent inhibit...

  2. Emergence of multicluster chimera states

    Yao, Nan; Huang, Zi-Gang; Grebogi, Celso; Lai, Ying-Cheng

    2015-09-01

    A remarkable phenomenon in spatiotemporal dynamical systems is chimera state, where the structurally and dynamically identical oscillators in a coupled networked system spontaneously break into two groups, one exhibiting coherent motion and another incoherent. This phenomenon was typically studied in the setting of non-local coupling configurations. We ask what can happen to chimera states under systematic changes to the network structure when links are removed from the network in an orderly fashion but the local coupling topology remains invariant with respect to an index shift. We find the emergence of multicluster chimera states. Remarkably, as a parameter characterizing the amount of link removal is increased, chimera states of distinct numbers of clusters emerge and persist in different parameter regions. We develop a phenomenological theory, based on enhanced or reduced interactions among oscillators in different spatial groups, to explain why chimera states of certain numbers of clusters occur in certain parameter regions. The theoretical prediction agrees well with numerics.

  3. Immune tolerance in radiation chimeras

    Establishment of immune tolerance in radiation chimeras and the mechanism of maintaining it were discussed from certain points. Semiallogeneic radiation chimeras are mostly of long-living, and the hematopoietic organ of this individual consists mainly of the cells derived from the marrow donor, i. e., F1-type cells. F1-type lymphocytes can distinguish parental strain cells from themselves. In these chimeras, a F1-skin graft maintains to be fresh as long as the host is alive, showing immune tolerance effective through its life. In establishment and maintenance of this immune tolerance, the suppressing mechanism of host-type or F1-type seems to be involved. The allogeneic radiation chimera has very poor long-survival rate compared with that of the semiallogeneic radiation chimera. To raise this survival rate, efforts are now being made from the immunological point of view. (Ueda, J.)

  4. Recurrence quantification analysis of chimera states

    Santos, M.S. [Pós-Graduação em Ciências/Física, Universidade Estadual de Ponta Grossa, 84030-900, Ponta Grossa, PR (Brazil); Szezech, J.D., E-mail: jdanilo@gmail.com [Departamento de Matemática e Estatística, Universidade Estadual de Ponta Grossa, 84030-900, Ponta Grossa, PR (Brazil); Batista, A.M., E-mail: antoniomarcosbatista@gmail.com [Departamento de Matemática e Estatística, Universidade Estadual de Ponta Grossa, 84030-900, Ponta Grossa, PR (Brazil); Caldas, I.L. [Instituto de Física, Universidade de São Paulo, 05315-970, São Paulo, SP (Brazil); Viana, R.L.; Lopes, S.R. [Departamento de Física, Universidade Federal do Paraná, 81531-990, Curitiba, PR (Brazil)

    2015-10-02

    Chimera states, characterised by coexistence of coherence and incoherence in coupled dynamical systems, have been found in various physical systems, such as mechanical oscillator networks and Josephson-junction arrays. We used recurrence plots to provide graphical representations of recurrent patterns and identify chimera states. Moreover, we show that recurrence plots can be used as a diagnostic of chimera states and also to identify the chimera collapse. - Highlights: • Chimera states have been found in various physical systems. • Recurrence plots is a graphical method useful to locate recurring patterns. • We used recurrence plots to identify the chimera states. • We show also the recurrence plots can identify the chimera collapse.

  5. Recurrence quantification analysis of chimera states

    Chimera states, characterised by coexistence of coherence and incoherence in coupled dynamical systems, have been found in various physical systems, such as mechanical oscillator networks and Josephson-junction arrays. We used recurrence plots to provide graphical representations of recurrent patterns and identify chimera states. Moreover, we show that recurrence plots can be used as a diagnostic of chimera states and also to identify the chimera collapse. - Highlights: • Chimera states have been found in various physical systems. • Recurrence plots is a graphical method useful to locate recurring patterns. • We used recurrence plots to identify the chimera states. • We show also the recurrence plots can identify the chimera collapse

  6. Nuclear receptor NR5A2 controls neural stem cell fate decisions during development

    Stergiopoulos, Athanasios; Politis, Panagiotis K.

    2016-01-01

    The enormous complexity of mammalian central nervous system (CNS) is generated by highly synchronized actions of diverse factors and signalling molecules in neural stem/progenitor cells (NSCs). However, the molecular mechanisms that integrate extrinsic and intrinsic signals to control proliferation versus differentiation decisions of NSCs are not well-understood. Here we identify nuclear receptor NR5A2 as a central node in these regulatory networks and key player in neural development. Overexpression and loss-of-function experiments in primary NSCs and mouse embryos suggest that NR5A2 synchronizes cell-cycle exit with induction of neurogenesis and inhibition of astrogliogenesis by direct regulatory effects on Ink4/Arf locus, Prox1, a downstream target of proneural genes, as well as Notch1 and JAK/STAT signalling pathways. Upstream of NR5a2, proneural genes, as well as Notch1 and JAK/STAT pathways control NR5a2 endogenous expression. Collectively, these observations render NR5A2 a critical regulator of neural development and target gene for NSC-based treatments of CNS-related diseases. PMID:27447294

  7. Cellular automaton for chimera states

    García-Morales, Vladimir

    2016-04-01

    A minimalistic model for chimera states is presented. The model is a cellular automaton (CA) which depends on only one adjustable parameter, the range of the nonlocal coupling, and is built from elementary cellular automata and the majority (voting) rule. This suggests the universality of chimera-like behavior from a new point of view: Already simple CA rules based on the majority rule exhibit this behavior. After a short transient, we find chimera states for arbitrary initial conditions, the system spontaneously splitting into stable domains separated by static boundaries, some synchronously oscillating and the others incoherent. When the coupling range is local, nontrivial coherent structures with different periodicities are formed.

  8. Enstore with Chimera namespace provider

    Enstore is a mass storage system developed by Fermilab that provides distributed access and management of data stored on tapes. It uses a namespace service, PNFS, developed by DESY to provide a filesystem-like view of the stored data. PNFS is a legacy product and is being replaced by a new implementation, called Chimera, which is also developed by DESY. Chimera offers multiple advantages over PNFS in terms of performance and functionality. The Enstore client component, encp, has been modified to work with Chimera, as well as with any other namespace provider. We performed high load end-to-end acceptance test of Enstore with the Chimera namespace. This paper describes the modifications to Enstore, the test procedure and the results of the acceptance testing.

  9. Emergence of multicluster chimera states

    Nan Yao; Zi-Gang Huang; Celso Grebogi; Ying-Cheng Lai

    2015-01-01

    A remarkable phenomenon in spatiotemporal dynamical systems is chimera state, where the structurally and dynamically identical oscillators in a coupled networked system spontaneously break into two groups, one exhibiting coherent motion and another incoherent. This phenomenon was typically studied in the setting of non-local coupling configurations. We ask what can happen to chimera states under systematic changes to the network structure when links are removed from the network in an orderly ...

  10. Chimera states in Star Networks

    Meena, Chandrakala; Murali, K.; Sinha, Sudeshna

    2015-01-01

    We consider star networks of chaotic oscillators, with all end-nodes connected only to the central hub node, under diffusive coupling, conjugate coupling and mean-field type coupling. We observe the existence of chimeras in the end-nodes, which are identical in terms of the coupling environment and dynamical equations. Namely, the symmetry of the end-nodes is broken and co-existing groups with different synchronization features and attractor geometries emerge. Surprisingly, such chimera state...

  11. Chimera order in spin systems

    Singh, Rajeev; Dasgupta, Subinay; Sinha, Sitabhra

    2010-01-01

    Homogeneous populations of oscillators have recently been shown to exhibit stable coexistence of coherent and incoherent regions. Generalizing the concept of chimera states to the context of order-disorder transition in systems at thermal equilibrium, we show analytically that such complex ordering can appear in a system of Ising spins, possibly the simplest physical system exhibiting this phenomenon. We also show numerically the existence of chimera ordering in 3-dimensional spin systems tha...

  12. Chimera States for Coupled Oscillators

    Abrams, Daniel M.; Strogatz, Steven H.

    2004-01-01

    Arrays of identical oscillators can display a remarkable spatiotemporal pattern in which phase-locked oscillators coexist with drifting ones. Discovered two years ago, such "chimera states" are believed to be impossible for locally or globally coupled systems; they are peculiar to the intermediate case of nonlocal coupling. Here we present an exact solution for this state, for a ring of phase oscillators coupled by a cosine kernel. We show that the stable chimera state bifurcates from a spati...

  13. Chimera and globally clustered chimera: Impact of time delay

    Sheeba, Jane H; Lakshmanan, M

    2010-01-01

    Following a short report of our preliminary results [Phys. Rev. E 79, 055203(R) (2009)], we present a more detailed study of the effects of coupling delay in diffusively coupled phase oscillator populations. We find that coupling delay induces chimera and globally clustered chimera (GCC) states in delay coupled populations. We show the existence of multi-clustered states that act as link between the chimera and the GCC states. A stable GCC state goes through a variety of GCC states, namely periodic, aperiodic, long-- and short--period breathers and becomes unstable GCC leading to global synchronization in the system, on increasing time delay. We provide numerical evidence and theoretical explanations for the above results and discuss possible applications of the observed phenomena.

  14. Chimera states in three dimensions

    Maistrenko, Yuri; Sudakov, Oleksandr; Osiv, Oleksiy; Maistrenko, Volodymyr

    2015-07-01

    The chimera state is a recently discovered dynamical phenomenon in arrays of nonlocally coupled oscillators, that displays a self-organized spatial pattern of coexisting coherence and incoherence. In this paper, the first evidence of three-dimensional chimera states is reported for the Kuramoto model of phase oscillators in 3D grid topology with periodic boundary conditions. Systematic analysis of the dependence of the spatiotemporal dynamics on the range and strength of coupling shows that there are two principal classes of the chimera patterns which exist in large domains of the parameter space: (I) oscillating and (II) spirally rotating. Characteristic examples from the first class include coherent as well as incoherent balls, tubes, crosses, and layers in incoherent or coherent surrounding; the second class includes scroll waves with incoherent, randomized rolls of different modality and dynamics. Numerical simulations started from various initial conditions indicate that the states are stable over the integration time. Videos of the dynamics of the chimera states are presented in supplementary material. It is concluded that three-dimensional chimera states, which are novel spatiotemporal patterns involving the coexistence of coherent and incoherent domains, can represent one of the inherent features of nature.

  15. Recurrence quantification analysis of chimera states

    Santos, M. S.; Szezech, J. D.; Batista, A. M.; Caldas, I. L.; Viana, R. L.; Lopes, S. R.

    2015-10-01

    Chimera states, characterised by coexistence of coherence and incoherence in coupled dynamical systems, have been found in various physical systems, such as mechanical oscillator networks and Josephson-junction arrays. We used recurrence plots to provide graphical representations of recurrent patterns and identify chimera states. Moreover, we show that recurrence plots can be used as a diagnostic of chimera states and also to identify the chimera collapse.

  16. Emergence of chimera in multiplex network

    Ghosh, Saptarshi; Jalan, Sarika

    2015-01-01

    Chimera is a relatively new emerging phenomenon where coexistence of synchronous and asynchronous state is observed in symmetrically coupled dynamical units. We report observation of the chimera state in multiplex networks where individual layer is represented by 1-d lattice with non-local interactions. While, multiplexing does not change the type of the chimera state and retains the multi-chimera state displayed by the isolated networks, it changes the regions of the incoherence. We investig...

  17. Petascale Supernova Simulation with CHIMERA

    CHIMERA is a multi-dimensional radiation hydrodynamics code designed to study core-collapse supernovae. The code is made up of three essentially independent parts: a hydrodynamics module, a nuclear burning module, and a neutrino transport solver combined within an operator-split approach. We describe some major algorithmic facets of the code and briefly discuss some recent results. The multi-physics nature of the problem, and the specific implementation of that physics in CHIMERA, provide a rather straightforward path to effective use of multi-core platforms in the near future

  18. Receptor residence time trumps drug-likeness and oral bioavailability in determining efficacy of complement C5a antagonists.

    Seow, Vernon; Lim, Junxian; Cotterell, Adam J; Yau, Mei-Kwan; Xu, Weijun; Lohman, Rink-Jan; Kok, W Mei; Stoermer, Martin J; Sweet, Matthew J; Reid, Robert C; Suen, Jacky Y; Fairlie, David P

    2016-01-01

    Drug discovery and translation are normally based on optimizing efficacy by increasing receptor affinity, functional potency, drug-likeness (rule-of-five compliance) and oral bioavailability. Here we demonstrate that residence time of a compound on its receptor has an overriding influence on efficacy, exemplified for antagonists of inflammatory protein complement C5a that activates immune cells and promotes disease. Three equipotent antagonists (3D53, W54011, JJ47) of inflammatory responses to C5a (3nM) were compared for drug-likeness, receptor affinity and antagonist potency in human macrophages, and anti-inflammatory efficacy in rats. Only the least drug-like antagonist (3D53) maintained potency in cells against higher C5a concentrations and had a much longer duration of action (t1/2 ~ 20 h) than W54011 or JJ47 (t1/2 ~ 1-3 h) in inhibiting macrophage responses. The unusually long residence time of 3D53 on its receptor was mechanistically probed by molecular dynamics simulations, which revealed long-lasting interactions that trap the antagonist within the receptor. Despite negligible oral bioavailability, 3D53 was much more orally efficacious than W54011 or JJ47 in preventing repeated agonist insults to induce rat paw oedema over 24 h. Thus, residence time on a receptor can trump drug-likeness in determining efficacy, even oral efficacy, of pharmacological agents. PMID:27094554

  19. Receptor residence time trumps drug-likeness and oral bioavailability in determining efficacy of complement C5a antagonists

    Seow, Vernon; Lim, Junxian; Cotterell, Adam J.; Yau, Mei-Kwan; Xu, Weijun; Lohman, Rink-Jan; Kok, W. Mei; Stoermer, Martin J.; Sweet, Matthew J.; Reid, Robert C.; Suen, Jacky Y.; Fairlie, David P.

    2016-01-01

    Drug discovery and translation are normally based on optimizing efficacy by increasing receptor affinity, functional potency, drug-likeness (rule-of-five compliance) and oral bioavailability. Here we demonstrate that residence time of a compound on its receptor has an overriding influence on efficacy, exemplified for antagonists of inflammatory protein complement C5a that activates immune cells and promotes disease. Three equipotent antagonists (3D53, W54011, JJ47) of inflammatory responses to C5a (3nM) were compared for drug-likeness, receptor affinity and antagonist potency in human macrophages, and anti-inflammatory efficacy in rats. Only the least drug-like antagonist (3D53) maintained potency in cells against higher C5a concentrations and had a much longer duration of action (t1/2 ~ 20 h) than W54011 or JJ47 (t1/2 ~ 1–3 h) in inhibiting macrophage responses. The unusually long residence time of 3D53 on its receptor was mechanistically probed by molecular dynamics simulations, which revealed long-lasting interactions that trap the antagonist within the receptor. Despite negligible oral bioavailability, 3D53 was much more orally efficacious than W54011 or JJ47 in preventing repeated agonist insults to induce rat paw oedema over 24 h. Thus, residence time on a receptor can trump drug-likeness in determining efficacy, even oral efficacy, of pharmacological agents. PMID:27094554

  20. Receptor residence time trumps drug-likeness and oral bioavailability in determining efficacy of complement C5a antagonists

    Seow, Vernon; Lim, Junxian; Cotterell, Adam J.; Yau, Mei-Kwan; Xu, Weijun; Lohman, Rink-Jan; Kok, W. Mei; Stoermer, Martin J.; Sweet, Matthew J.; Reid, Robert C.; Suen, Jacky Y.; Fairlie, David P.

    2016-04-01

    Drug discovery and translation are normally based on optimizing efficacy by increasing receptor affinity, functional potency, drug-likeness (rule-of-five compliance) and oral bioavailability. Here we demonstrate that residence time of a compound on its receptor has an overriding influence on efficacy, exemplified for antagonists of inflammatory protein complement C5a that activates immune cells and promotes disease. Three equipotent antagonists (3D53, W54011, JJ47) of inflammatory responses to C5a (3nM) were compared for drug-likeness, receptor affinity and antagonist potency in human macrophages, and anti-inflammatory efficacy in rats. Only the least drug-like antagonist (3D53) maintained potency in cells against higher C5a concentrations and had a much longer duration of action (t1/2 ~ 20 h) than W54011 or JJ47 (t1/2 ~ 1–3 h) in inhibiting macrophage responses. The unusually long residence time of 3D53 on its receptor was mechanistically probed by molecular dynamics simulations, which revealed long-lasting interactions that trap the antagonist within the receptor. Despite negligible oral bioavailability, 3D53 was much more orally efficacious than W54011 or JJ47 in preventing repeated agonist insults to induce rat paw oedema over 24 h. Thus, residence time on a receptor can trump drug-likeness in determining efficacy, even oral efficacy, of pharmacological agents.

  1. In vivo antinociception of potent mu opioid agonist tetrapeptide analogues and comparison with a compact opioid agonist - neurokinin 1 receptor antagonist chimera

    Guillemyn Karel

    2012-01-01

    Full Text Available Abstract Background An important limiting factor in the development of centrally acting pharmaceuticals is the blood-brain barrier (BBB. Transport of therapeutic peptides through this highly protective physiological barrier remains a challenge for peptide drug delivery into the central nervous system (CNS. Because the most common strategy to treat moderate to severe pain consists of the activation of opioid receptors in the brain, the development of active opioid peptide analogues as potential analgesics requires compounds with a high resistance to enzymatic degradation and an ability to cross the BBB. Results Herein we report that tetrapeptide analogues of the type H-Dmt1-Xxx2-Yyy3-Gly4-NH2 are transported into the brain after intravenous and subcutaneous administration and are able to activate the μ- and δ opioid receptors more efficiently and over longer periods of time than morphine. Using the hot water tail flick test as the animal model for antinociception, a comparison in potency is presented between a side chain conformationally constrained analogue containing the benzazepine ring (BVD03, Yyy3: Aba, and a "ring opened" analogue (BVD02, Yyy3: Phe. The results show that in addition to the increased lipophilicity through amide bond N-methylation, the conformational constraint introduced at the level of the Phe3 side chain causes a prolonged antinociception. Further replacement of NMe-D-Ala2 by D-Arg2 in the tetrapeptide sequence led to an improved potency as demonstrated by a higher and maintained antinociception for AN81 (Xxx2: D-Arg vs. BVD03 (Xxx2: NMe-D-Ala. A daily injection of the studied opioid ligands over a time period of 5 days did however result in a substantial decrease in antinociception on the fifth day of the experiment. The compact opioid agonist - NK1 antagonist hybrid SBCHM01 could not circumvent opioid induced tolerance. Conclusions We demonstrated that the introduction of a conformational constraint has an important

  2. Association of Immune and Metabolic Receptors C5aR and C5L2 with Adiposity in Women

    Pegah Poursharifi

    2014-01-01

    Full Text Available Adipose tissue receptors C5aR and C5L2 and their heterodimerization/functionality and interaction with ligands C5a and acylation stimulating protein (ASP have been evaluated in cell and rodent studies. Their contribution to obesity factors in humans remains unclear. We hypothesized that C5a receptors, classically required for host defense, are also associated with adiposity. Anthropometry and fasting blood parameters were measured in 136 women divided by body mass index (BMI: normal/overweight (≤30 kg/m2; n = 34, obese I (≤45 kg/m2; n = 33, obese II (≤51 kg/m2; n = 33, and obese III (≤80 kg/m2; n = 36. Subcutaneous and omental adipose tissue C5aR and C5L2 expression were analysed. C5L2 expression was comparable between subcutaneous and omental across all BMI groups. Plasma ASP and ASP/omental C5L2 expression increased with BMI (P < 0.001 and P < 0.01, resp.. While plasma C5a was unchanged, C5aR expression decreased with increasing BMI in subcutaneous and omental tissues (P < 0.01 and P < 0.05, resp., with subcutaneous omental depots. Omental C5L2/C5aR ratio increased with BMI (P < 0.01 with correlations between C5L2/C5aR and waist circumference, HDL-C, and adiponectin. Tissue and BMI differences in receptors and ligands, particularly in omental, suggest relationship to metabolic disturbances and highlight adipose-immune interactions.

  3. Structural complexes of the agonist, inverse agonist and antagonist bound C5a receptor: insights into pharmacology and signaling.

    Rana, Soumendra; Sahoo, Amita Rani; Majhi, Bharat Kumar

    2016-04-26

    The C5a receptor (C5aR) is a pharmacologically important G-protein coupled receptor (GPCR) that interacts with (h)C5a, by recruiting both the "orthosteric" sites (site1 at the N-terminus and site2 at the ECS, extra cellular surface) on C5aR in a two site-binding model. However, the complex pharmacological landscape and the distinguishing chemistry operating either at the "orthosteric" site1 or at the functionally important "orthosteric" site2 of C5aR are still not clear, which greatly limits the understanding of C5aR pharmacology. One of the major bottlenecks is the lack of an experimental structure or a refined model structure of C5aR with appropriately defined active sites. The study attempts to understand the pharmacology at the "orthosteric" site2 of C5aR rationally by generating a highly refined full-blown model structure of C5aR through advanced molecular modeling techniques, and further subjecting it to automated docking and molecular dynamics (MD) studies in the POPC bilayer. The first series of structural complexes of C5aR respectively bound to a linear native peptide agonist ((h)C5a-CT), a small molecule inverse agonist (NDT) and a cyclic peptide antagonist (PMX53) are reported, apparently establishing the unique pharmacological landscape of the "orthosteric" site2, which also illustrates an energetically distinct but coherent competitive chemistry ("cation-π" vs. "π-π" interactions) involved in distinguishing the established ligands known for targeting the "orthosteric" site2 of C5aR. Over a total of 1 μs molecular dynamics (MD) simulation in the POPC bilayer, it is evidenced that while the agonist prefers a "cation-π" interaction, the inverse agonist prefers a "cogwheel/L-shaped" interaction in contrast to the "edge-to-face/T-shaped" type π-π interactions demonstrated by the antagonist by engaging the F275(7.28) of the C5aR. In the absence of a NMR or crystallographically guided model structure of C5aR, the computational model complexes not only

  4. Recent results of CHIMERA activity

    Pagano A.

    2012-07-01

    Full Text Available The experimental activity of CHIMERA in recent years has been characterized by a steady progress in the detection technique and data analysis. Since 2008 the detector system benefits of new implementations: a new reaction chamber, a new charged particle identification in silicon detector made by an extended pulse shape method and an efficient system for the identification of exotic beams produced by projectile-like fragmentation (In-flight method. These implementations appear to be promising tools in view of further exclusive experiments in the field of isospin physics. The coupling of CHIMERA with other equipments (such as interferometers and highly segmented arrays, magnetic elements, neutron detectors, etc. is also envisaged in order to extend the studies of the reaction mechanism in heavy ion physics.

  5. A Tweezer for Chimeras in Small Networks

    Omelchenko, Iryna; Omel'chenko, Oleh E.; Zakharova, Anna; Wolfrum, Matthias; Schoell, Eckehard

    2015-01-01

    We propose a control scheme which can stabilize and fix the position of chimera states in small networks. Chimeras consist of coexisting domains of spatially coherent and incoherent dynamics in systems of nonlocally coupled identical oscillators. Chimera states are generally difficult to observe in small networks due to their short lifetime and erratic drifting of the spatial position of the incoherent domain. The control scheme, like a tweezer, might be useful in experiments, where usually o...

  6. Tweezers for Chimeras in Small Networks

    Omelchenko, Iryna; Omel'chenko, Oleh E.; Zakharova, Anna; Wolfrum, Matthias; Schöll, Eckehard

    2016-03-01

    We propose a control scheme which can stabilize and fix the position of chimera states in small networks. Chimeras consist of coexisting domains of spatially coherent and incoherent dynamics in systems of nonlocally coupled identical oscillators. Chimera states are generally difficult to observe in small networks due to their short lifetime and erratic drifting of the spatial position of the incoherent domain. The control scheme, like a tweezer, might be useful in experiments, where usually only small networks can be realized.

  7. Chimera patterns under the impact of noise

    Loos, Sarah A. M.; Claussen, Jens Christian; Schöll, Eckehard; Zakharova, Anna

    2015-01-01

    We investigate two types of chimera states, i.e., patterns consisting of coexisting spatially separated domains with coherent and incoherent dynamics, in ring networks of Stuart-Landau oscillators with symmetry-breaking coupling, under the influence of noise. Amplitude chimeras are characterized by temporally periodic dynamics throughout the whole network, but spatially incoherent behavior with respect to the amplitudes in a part of the system; they are long-living transients. Chimera death s...

  8. Enhancing UCSF Chimera through web services

    Huang, CC; Meng, EC; Morris, JH; Pettersen, EF; Ferrin, TE

    2014-01-01

    Integrating access to web services with desktop applications allows for an expanded set of application features, including performing computationally intensive tasks and convenient searches of databases. We describe how we have enhanced UCSF Chimera (http://www.rbvi.ucsf.edu/chimera/), a program for the interactive visualization and analysis of molecular structures and related data, through the addition of several web services (http://www.rbvi.ucsf.edu/chimera/ docs/webservices.html). By stre...

  9. Metabotropic glutamate receptor 5 - a promising target in drug development and neuroimaging

    Pillai, Rajapillai L.I.; Tipre, Dnyanesh N. [Stony Brook University Health Science Center, Department of Psychiatry, Stony Brook, NY (United States)

    2016-06-15

    This review summarizes the contributions by various teams of scientists in assessing the metabotropic glutamate receptor 5 (mGluR5) as a biomarker in neuropsychiatric disorders and diseases. Development of positive and negative allosteric modulators of mGluR5 is reviewed, as is the development of PET radioligands that have the potential to measure mGluR5 receptor density in neurological disorders and during therapeutic interventions. PET imaging provides an effective tool to assess the specificity of new drugs, select dose regimens in clinical trials, and study drug mechanisms of action. We summarize and deliver comparative analyses of mGluR5-specific PET radiotracers and their applications in understanding the pathophysiology of mGluR5-related nervous system disorders and to speed up drug development. (orig.)

  10. Chimera patterns under the impact of noise

    Loos, Sarah A. M.; Claussen, Jens Christian; Schöll, Eckehard; Zakharova, Anna

    2016-01-01

    We investigate two types of chimera states, patterns consisting of coexisting spatially separated domains with coherent and incoherent dynamics, in ring networks of Stuart-Landau oscillators with symmetry-breaking coupling, under the influence of noise. Amplitude chimeras are characterized by temporally periodic dynamics throughout the whole network, but spatially incoherent behavior with respect to the amplitudes in a part of the system; they are long-living transients. Chimera death states generalize chimeras to stationary inhomogeneous patterns (oscillation death), which combine spatially coherent and incoherent domains. We analyze the impact of random perturbations, addressing the question of robustness of chimera states in the presence of white noise. We further consider the effect of symmetries applied to random initial conditions.

  11. Imperfect chimera states for coupled pendula.

    Kapitaniak, Tomasz; Kuzma, Patrycja; Wojewoda, Jerzy; Czolczynski, Krzysztof; Maistrenko, Yuri

    2014-01-01

    The phenomenon of chimera states in the systems of coupled, identical oscillators has attracted a great deal of recent theoretical and experimental interest. In such a state, different groups of oscillators can exhibit coexisting synchronous and incoherent behaviors despite homogeneous coupling. Here, considering the coupled pendula, we find another pattern, the so-called imperfect chimera state, which is characterized by a certain number of oscillators which escape from the synchronized chimera's cluster or behave differently than most of uncorrelated pendula. The escaped elements oscillate with different average frequencies (Poincare rotation number). We show that imperfect chimera can be realized in simple experiments with mechanical oscillators, namely Huygens clock. The mathematical model of our experiment shows that the observed chimera states are controlled by elementary dynamical equations derived from Newton's laws that are ubiquitous in many physical and engineering systems. PMID:25223296

  12. Activation of nuclear receptor NR5A2 increases Glut4 expression and glucose metabolism in muscle cells

    Highlights: • NR5A2 expression in C2C12 is associated with myotube differentiation. • DLPC induces an increase in GLUT4 levels and glucose uptake in C2C12 myotubes. • In high glucose conditions the activation of NR5A2 inhibits fatty acids oxidation. - Abstract: NR5A2 is a nuclear receptor which regulates the expression of genes involved in cholesterol metabolism, pluripotency maintenance and cell differentiation. It has been recently shown that DLPC, a NR5A2 ligand, prevents liver steatosis and improves insulin sensitivity in mouse models of insulin resistance, an effect that has been associated with changes in glucose and fatty acids metabolism in liver. Because skeletal muscle is a major tissue in clearing glucose from blood, we studied the effect of the activation of NR5A2 on muscle metabolism by using cultures of C2C12, a mouse-derived cell line widely used as a model of skeletal muscle. Treatment of C2C12 with DLPC resulted in increased levels of expression of GLUT4 and also of several genes related to glycolysis and glycogen metabolism. These changes were accompanied by an increased glucose uptake. In addition, the activation of NR5A2 produced a reduction in the oxidation of fatty acids, an effect which disappeared in low-glucose conditions. Our results suggest that NR5A2, mostly by enhancing glucose uptake, switches muscle cells into a state of glucose preference. The increased use of glucose by muscle might constitute another mechanism by which NR5A2 improves blood glucose levels and restores insulin sensitivity

  13. Activation of nuclear receptor NR5A2 increases Glut4 expression and glucose metabolism in muscle cells

    Bolado-Carrancio, A. [Department of Molecular Biology, University of Cantabria, IDIVAL, Santander (Spain); Riancho, J.A. [Department of Internal Medicine, Hospital U.M. Valdecilla-IDIVAL, University of Cantabria, RETICEF, Santander (Spain); Sainz, J. [Institute of Biomedicine and Biotechnology of Cantabria (IBBTEC), CSIC-University of Cantabria, Santander (Spain); Rodríguez-Rey, J.C., E-mail: rodriguj@unican.es [Department of Molecular Biology, University of Cantabria, IDIVAL, Santander (Spain)

    2014-04-04

    Highlights: • NR5A2 expression in C2C12 is associated with myotube differentiation. • DLPC induces an increase in GLUT4 levels and glucose uptake in C2C12 myotubes. • In high glucose conditions the activation of NR5A2 inhibits fatty acids oxidation. - Abstract: NR5A2 is a nuclear receptor which regulates the expression of genes involved in cholesterol metabolism, pluripotency maintenance and cell differentiation. It has been recently shown that DLPC, a NR5A2 ligand, prevents liver steatosis and improves insulin sensitivity in mouse models of insulin resistance, an effect that has been associated with changes in glucose and fatty acids metabolism in liver. Because skeletal muscle is a major tissue in clearing glucose from blood, we studied the effect of the activation of NR5A2 on muscle metabolism by using cultures of C2C12, a mouse-derived cell line widely used as a model of skeletal muscle. Treatment of C2C12 with DLPC resulted in increased levels of expression of GLUT4 and also of several genes related to glycolysis and glycogen metabolism. These changes were accompanied by an increased glucose uptake. In addition, the activation of NR5A2 produced a reduction in the oxidation of fatty acids, an effect which disappeared in low-glucose conditions. Our results suggest that NR5A2, mostly by enhancing glucose uptake, switches muscle cells into a state of glucose preference. The increased use of glucose by muscle might constitute another mechanism by which NR5A2 improves blood glucose levels and restores insulin sensitivity.

  14. Secondary Disease in Radiation Chimeras

    A review of research dealing directly or indirectly with the development of bidirectional tolerance in radiation chimeras has been made, emphasizing some of the contemporary research on this subject in Oak Ridge and Knoxville. By controlling such factors as cell dose, age of donor animal and day of cell injection, it was possible to achieve bidirectional tolerance. Attempts to reduce bidirectional tolerance in favour of increasing the graft-versus-host reaction were less successful. Hypoxic caging demonstrated a new approach to achieving bidirectional tolerance through physiological competition for growth. Graft-versus-host reactions have a lower growth priority than marrow regeneration or erythropoietic hyperplasia. Study of pathologic processes, immunologic capability and the-biochemical lesions in radiation chimeras all lead to new ideas that involve bidirectional tolerance. The investigations on dose rate in radiation suppression of the immune response and on LD50 (30- to 90-day)values after injection of different numbers of marrow cells all have a bearing on control of the host-versus-graft response and therefore are important in understanding bidirectional tolerance. (author)

  15. Nerve Growth Factor Secretion From Pulp Fibroblasts is Modulated by Complement C5a Receptor and Implied in Neurite Outgrowth.

    Chmilewsky, Fanny; Ayaz, Warda; Appiah, James; About, Imad; Chung, Seung-Hyuk

    2016-01-01

    Given the importance of sensory innervation in tooth vitality, the identification of signals that control nerve regeneration and the cellular events they induce is essential. Previous studies demonstrated that the complement system, a major component of innate immunity and inflammation, is activated at the injured site of human carious teeth and plays an important role in dental-pulp regeneration via interaction of the active Complement C5a fragment with pulp progenitor cells. In this study, we further determined the role of the active fragment complement C5a receptor (C5aR) in dental nerve regeneration in regards to local secretion of nerve growth factor (NGF) upon carious injury. Using ELISA and AXIS co-culture systems, we demonstrate that C5aR is critically implicated in the modulation of NGF secretion by LTA-stimulated pulp fibroblasts. The NGF secretion by LTA-stimulated pulp fibroblasts, which is negatively regulated by C5aR activation, has a role in the control of the neurite outgrowth length in our axon regeneration analysis. Our data provide a scientific step forward that can guide development of future therapeutic tools for innovative and incipient interventions targeting the dentin-pulp regeneration process by linking the neurite outgrowth to human pulp fibroblast through complement system activation. PMID:27539194

  16. Emergence of Chimera in Multiplex Network

    Ghosh, Saptarshi; Jalan, Sarika

    2016-06-01

    Chimera is a relatively new emerging phenomenon where coexistence of synchronous and asynchronous states is observed in symmetrically coupled dynamical units. We report the observation of the chimera state in multiplex networks where individual layer is represented by 1-d lattice with nonlocal interactions. While, multiplexing does not change the type of the chimera state and retains the multi-chimera state displayed by the isolated networks, it changes the regions of the incoherence. We investigate the emergence of coherent-incoherent bifurcation upon varying the control parameters, namely, the coupling strength and the network size. Additionally, we investigate the effect of initial condition on the dynamics of the chimera state. Using a measure based on the differences between the neighboring nodes which distinguishes smooth and nonsmooth spatial profiles, we find the critical coupling strength for the transition to the chimera state. Observing chimera in a multiplex network with one-to-one inter layer coupling is important to gain insight to many real world complex systems which inherently posses multilayer architecture.

  17. Different kinds of chimera death states in nonlocally coupled oscillators

    Premalatha, K.; Chandrasekar, V. K.; Senthilvelan, M.; Lakshmanan, M.

    2015-01-01

    We investigate the significance of nonisochronicity parameter in a network of nonlocally coupled Stuart-Landau oscillators with symmetry breaking form. We observe that the presence of nonisochronicity parameter leads to structural changes in the chimera death region while varying the strength of the interaction. This gives rise to the existence of different types of chimera death states such as multi-chimera death state, type-I periodic chimera death (PCD) state and, type-II periodic chimera ...

  18. Chimeras in networks with purely local coupling

    Laing, Carlo R.

    2015-11-01

    Chimera states in spatially extended networks of oscillators have some oscillators synchronized while the remainder are asynchronous. These states have primarily been studied in networks with nonlocal coupling, and more recently in networks with global coupling. Here, we present three networks with only local coupling (diffusive, to nearest neighbors) which are numerically found to support chimera states. One of the networks is analyzed using a self-consistency argument in the continuum limit, and this is used to find the boundaries of existence of a chimera state in parameter space.

  19. Twisted chimera states and multicore spiral chimera states on a two-dimensional torus.

    Xie, Jianbo; Knobloch, Edgar; Kao, Hsien-Ching

    2015-10-01

    Chimera states consisting of domains of coherently and incoherently oscillating oscillators in a two-dimensional periodic array of nonlocally coupled phase oscillators are studied. In addition to the one-dimensional chimera states familiar from one spatial dimension, two-dimensional structures termed twisted chimera states and spiral wave chimera states are identified in simulations. The properties of many of these states, including stability, are determined using an evolution equation for a complex order parameter and are found to be in agreement with the simulations. PMID:26565318

  20. Twisted chimera states and multicore spiral chimera states on a two-dimensional torus

    Xie, Jianbo; Knobloch, Edgar; Kao, Hsien-Ching

    2015-10-01

    Chimera states consisting of domains of coherently and incoherently oscillating oscillators in a two-dimensional periodic array of nonlocally coupled phase oscillators are studied. In addition to the one-dimensional chimera states familiar from one spatial dimension, two-dimensional structures termed twisted chimera states and spiral wave chimera states are identified in simulations. The properties of many of these states, including stability, are determined using an evolution equation for a complex order parameter and are found to be in agreement with the simulations.

  1. Chimeras

    Huther, Constanze

    2009-01-01

    What types of human-animal interspecific entities are used in biomedical research? Is creating such entities morally wrong? And what do interspecifics tell us about the moral significance of species? This thesis offers an introduction to the field of human-animal interspecifics from a bioethical perspective, with a special focus on the question of speciesism.

  2. Generation of axolotl hematopoietic chimeras

    David Lopez

    2015-02-01

    Full Text Available Wound repair is an extremely complex process that requires precise coordination between various cell types including immune cells.  Unfortunately, in mammals this usually results in scar formation instead of restoration of the original fully functional tissue, otherwise known as regeneration.  Various animal models like frogs and salamanders are currently being studied to determine the intracellular and intercellular pathways, controlled by gene expression, that elicit cell proliferation, differentiation, and migration of cells during regenerative healing.  Now, the necessary genetic tools to map regenerative pathways are becoming available for the axolotl salamander, thus allowing comparative studies between scarring and regeneration.  Here, we describe in detail three methods to produce axolotl hematopoietic cell-tagged chimeras for the study of hematopoiesis and regeneration.

  3. HIRENASD Chimera medium-size grid

    National Aeronautics and Space Administration — Chimera medium-size grid for HIRENASD. Two files, fort.501 for grid for wing, fuselage, and 'world' zones, fort.503 for collar zone. File format is plot3d,...

  4. Allogeneic radiation chimeras induced in SPF mice

    During the past two decades much has been learned concerning the immunobiology of bone marrow chimeras induced in experimental animals as well as in man. However, from the basic as well as clinical points of view, there still remain many unsolved questions yet to be resolved. In this presentation, we discussed some of our recent results on the immunobiology of radiation chimeras induced in specific-pathogen-free (SPF) mice. These included the following: (a) contribution of graft versus host reaction (GVHR) as well non- GVHR mediated immunologic mechanism(s) to the expression of immunologic dysfunctions observed in allogeneic and certain semiallogeneic chimeras, (b) existence of immunoregulatory mechanism as a basis for the apparent lack of immunologic reactivity (tolerance) to the host- as well as to the donor-type alloantigens in situ in successful allogeneic bone marrow chimeras, and (c) the effect of microflora of the environment on the stability of such immunoregulatory mechanisms and its possible mechanism of action. (auth.)

  5. Chimera States in Mechanical Oscillator Networks

    Martens, Erik Andreas; Fourrière, Antoine; Hallatschek, Oskar

    2013-01-01

    The synchronization of coupled oscillators is a fascinating manifestation of self-organization that nature employs to orchestrate essential processes of life, such as the beating of the heart. While it was long thought that synchrony or disorder were mutually exclusive steady states for a network of identical oscillators, numerous theoretical studies in recent years revealed the intriguing possibility of 'chimera states', in which the symmetry of the oscillator population is broken into a synchronous and an asynchronous part. However, a striking lack of empirical evidence raises the question of whether chimeras are indeed characteristic to natural systems. This calls for a palpable realization of chimera states without any fine-tuning, from which physical mechanisms underlying their emergence can be uncovered. Here, we devise a simple experiment with mechanical oscillators coupled in a hierarchical network to show that chimeras emerge naturally from a competition between two antagonistic synchronization patte...

  6. Binding domains of stimulatory and inhibitory thyrotropin (TSH) receptor autoantibodies determined with chimeric TSH-lutropin/chorionic gonadotropin receptors.

    Nagayama, Y; Wadsworth, H L; Russo, D.; Chazenbalk, G D; Rapoport, B

    1991-01-01

    We examined the relative effects of thyrotropin (TSH) and TSH receptor autoantibodies in the sera of patients with autoimmune thyroid disease on three TSH-lutropin/chorionic gonadotropin (LH/CG) receptor extracellular domain chimeras. Each chimera binds TSH with high affinity. Only the chimera with TSH receptor extracellular domains ABC (amino acids 1-260) had a functional (cAMP) response to thyroid stimulatory IgG. The chimeras with TSH receptor domains CD (amino acids 171-360) and DE (amino...

  7. N-formylpeptide and complement C5a receptors are expressed in liver cells and mediate hepatic acute phase gene regulation

    1995-01-01

    Although the classical chemotactic receptor for complement anaphylatoxin C5a has been associated with polymorphonuclear and mononuclear phagocytes, several recent studies have indicated that this receptor is expressed on nonmyeloid cells including human endothelial cells, vascular smooth muscle cells, bronchial and alveolar epithelial cells, hepatocytes, and in the human hepatoma cell line HepG2. In this study, we examined the possibility that other members of the chemotactic receptor family ...

  8. A classification scheme for chimera states

    Kemeth, Felix P.; Haugland, Sindre W.; Schmidt, Lennart; Kevrekidis, Ioannis G.; Krischer, Katharina

    2016-01-01

    We present a universal characterization scheme for chimera states applicable to both numerical and experimental data sets. The scheme is based on two correlation measures that enable a meaningful definition of chimera states as well as their classification into three categories: stationary, turbulent and breathing. In addition, these categories can be further subdivided according to the time-stationarity of these two measures. We demonstrate that this approach both is consistent with previous...

  9. Chimeras in networks with purely local coupling

    Laing, Carlo R.

    2015-01-01

    Chimera states in spatially extended networks of oscillators have some oscillators synchronised while the remainder are asynchronous. These states have primarily been studied in networks with nonlocal coupling, and more recently in networks with global coupling. Here we present three networks with only local coupling (diffusive, to nearest neighbours) which are numerically found to support chimera states. One of the networks is analysed using a self-consistency argument in the continuum limit...

  10. Chimera Death: Symmetry Breaking in Dynamical Networks

    Zakharova, Anna; Kapeller, Marie; Schöll, Eckehard

    2014-01-01

    For a network of generic oscillators with nonlocal topology and symmetry-breaking coupling we establish novel partially coherent inhomogeneous spatial patterns, which combine the features of chimera states (coexisting incongruous coherent and incoherent domains) and oscillation death (oscillation suppression), which we call chimera death. We show that due to the interplay of nonlocality and breaking of rotational symmetry by the coupling two distinct scenarios from oscillatory behavior to a s...

  11. Treatment with the C5a receptor antagonist ADC-1004 reduces myocardial infarction in a porcine ischemia-reperfusion model

    Arheden Håkan

    2010-09-01

    Full Text Available Abstract Background Polymorphonuclear neutrophils, stimulated by the activated complement factor C5a, have been implicated in cardiac ischemia/reperfusion injury. ADC-1004 is a competitive C5a receptor antagonist that has been shown to inhibit complement related neutrophil activation. ADC-1004 shields the neutrophils from C5a activation before they enter the reperfused area, which could be a mechanistic advantage compared to previous C5a directed reperfusion therapies. We investigated if treatment with ADC-1004, according to a clinically applicable protocol, would reduce infarct size and microvascular obstruction in a large animal myocardial infarct model. Methods In anesthetized pigs (42-53 kg, a percutaneous coronary intervention balloon was inflated in the left anterior descending artery for 40 minutes, followed by 4 hours of reperfusion. Twenty minutes after balloon inflation the pigs were randomized to an intravenous bolus administration of ADC-1004 (175 mg, n = 8 or saline (9 mg/ml, n = 8. Area at risk (AAR was evaluated by ex vivo SPECT. Infarct size and microvascular obstruction were evaluated by ex vivo MRI. The observers were blinded to the treatment at randomization and analysis. Results ADC-1004 treatment reduced infarct size by 21% (ADC-1004: 58.3 ± 3.4 vs control: 74.1 ± 2.9%AAR, p = 0.007. Microvascular obstruction was similar between the groups (ADC-1004: 2.2 ± 1.2 vs control: 5.3 ± 2.5%AAR, p = 0.23. The mean plasma concentration of ADC-1004 was 83 ± 8 nM at sacrifice. There were no significant differences between the groups with respect to heart rate, mean arterial pressure, cardiac output and blood-gas data. Conclusions ADC-1004 treatment reduces myocardial ischemia-reperfusion injury and represents a novel treatment strategy of myocardial infarct with potential clinical applicability.

  12. Correlation of androgen receptor and SRD5A2 gene mutations with pediatric hypospadias in 46, XY DSD children.

    Fu, X H; Zhang, W Q; Qu, X S

    2016-01-01

    We performed an exploratory study by analyzing the correlation of 46, XY disorders of sex development (46, XY DSD) with androgen receptor (AR) and steroid 5α-reductase-2 (SRD5A2) gene mutations and a safety analysis of dihydrotestosterone (DHT) gel treatment for pediatric micropenis. We collected samples from 76 pediatric patients with 46, XY DSD and 50 healthy adult men with normal fertility as the control group. The pediatric patients were treated with DHT gel (0.1-0.3 mg/kg/day) for three to six months. The extended penis length, testicular volume, and multiple blood parameters were collected before treatment and one, three, and six months after treatment. Of the 76 cases with 46, XY DSD, 31.58% had hypospadias with micropenis and 6.58% had male pseudohermaphroditism. Through AR gene screening, it was found that 14 patients had AR point mutations and 22 patients had SRD5A2 mutations. After treatment with DHT, the penis length of the patients significantly improved after one, three, and six months of treatment, with longer treatment times resulting in greater improvement. Before treatment with DHT, the average serum DHT value of patients with 46, XY DSD was 24.29 pg/mL. After one, three, and six months of treatment, this value increased to 430.71, 328.9, and 323.6 pg/mL, respectively. We conclude that for pediatric patients who have male hermaphroditism or hypospadias with micropenis, AR and SRD5A2 gene mutation detection should be performed. Local application of DHT gel can promote penis growth effectively without systemic adverse reactions. PMID:27051040

  13. Experimental Malaria in Pregnancy Induces Neurocognitive Injury in Uninfected Offspring via a C5a-C5a Receptor Dependent Pathway.

    Chloë R McDonald

    2015-09-01

    Full Text Available The in utero environment profoundly impacts childhood neurodevelopment and behaviour. A substantial proportion of pregnancies in Africa are at risk of malaria in pregnancy (MIP however the impact of in utero exposure to MIP on fetal neurodevelopment is unknown. Complement activation, in particular C5a, may contribute to neuropathology and adverse outcomes during MIP. We used an experimental model of MIP and standardized neurocognitive testing, MRI, micro-CT and HPLC analysis of neurotransmitter levels, to test the hypothesis that in utero exposure to malaria alters neurodevelopment through a C5a-C5aR dependent pathway. We show that malaria-exposed offspring have persistent neurocognitive deficits in memory and affective-like behaviour compared to unexposed controls. These deficits were associated with reduced regional brain levels of major biogenic amines and BDNF that were rescued by disruption of C5a-C5aR signaling using genetic and functional approaches. Our results demonstrate that experimental MIP induces neurocognitive deficits in offspring and suggest novel targets for intervention.

  14. Experimental Malaria in Pregnancy Induces Neurocognitive Injury in Uninfected Offspring via a C5a-C5a Receptor Dependent Pathway.

    McDonald, Chloë R; Cahill, Lindsay S; Ho, Keith T; Yang, Jimmy; Kim, Hani; Silver, Karlee L; Ward, Peter A; Mount, Howard T; Liles, W Conrad; Sled, John G; Kain, Kevin C

    2015-09-01

    The in utero environment profoundly impacts childhood neurodevelopment and behaviour. A substantial proportion of pregnancies in Africa are at risk of malaria in pregnancy (MIP) however the impact of in utero exposure to MIP on fetal neurodevelopment is unknown. Complement activation, in particular C5a, may contribute to neuropathology and adverse outcomes during MIP. We used an experimental model of MIP and standardized neurocognitive testing, MRI, micro-CT and HPLC analysis of neurotransmitter levels, to test the hypothesis that in utero exposure to malaria alters neurodevelopment through a C5a-C5aR dependent pathway. We show that malaria-exposed offspring have persistent neurocognitive deficits in memory and affective-like behaviour compared to unexposed controls. These deficits were associated with reduced regional brain levels of major biogenic amines and BDNF that were rescued by disruption of C5a-C5aR signaling using genetic and functional approaches. Our results demonstrate that experimental MIP induces neurocognitive deficits in offspring and suggest novel targets for intervention. PMID:26402732

  15. Differential Contributions of the Complement Anaphylotoxin Receptors C5aR1 and C5aR2 to the Early Innate Immune Response against Staphylococcus aureus Infection

    Sarah A. Horst

    2015-10-01

    Full Text Available The complement anaphylatoxin C5a contributes to host defense against Staphylococcus aureus. In this study, we investigated the functional role of the two known C5a receptors, C5aR1 and C5aR2, in the host response to S. aureus. We found that C5aR1−/− mice exhibited greater susceptibility to S. aureus bloodstream infection than wild type and C5aR2−/− mice, as demonstrated by the significantly higher bacterial loads in the kidneys and heart at 24 h of infection, and by the higher levels of inflammatory IL-6 in serum. Histological and immunohistochemistry investigation of infected kidneys at 24 h after bacterial inoculation revealed a discrete infiltration of neutrophils in wild type mice but already well-developed abscesses consisting of bacterial clusters surrounded by a large number of neutrophils in both C5aR1−/− and C5aR2−/− mice. Furthermore, blood neutrophils from C5aR1−/− mice were less efficient than those from wild type or C5aR2−/− mice at killing S. aureus. The requirement of C5aR1 for efficient killing of S. aureus was also demonstrated in human blood after disrupting C5a-C5aR1 signaling using specific inhibitors. These results demonstrated a role for C5aR1 in S. aureus clearance as well as a role for both C5aR1 and C5aR2 in the orchestration of the inflammatory response during infection.

  16. Imperfect traveling chimera states induced by local synaptic gradient coupling

    Bera, Bidesh K.; Ghosh, Dibakar; Banerjee, Tanmoy

    2016-07-01

    In this paper, we report the occurrence of chimera patterns in a network of neuronal oscillators, which are coupled through local, synaptic gradient coupling. We discover a new chimera pattern, namely the imperfect traveling chimera state, where the incoherent traveling domain spreads into the coherent domain of the network. Remarkably, we also find that chimera states arise even for one-way local coupling, which is in contrast to the earlier belief that only nonlocal, global, or nearest-neighbor local coupling can give rise to chimera state; this find further relaxes the essential connectivity requirement of getting a chimera state. We choose a network of identical bursting Hindmarsh-Rose neuronal oscillators, and we show that depending upon the relative strength of the synaptic and gradient coupling, several chimera patterns emerge. We map all the spatiotemporal behaviors in parameter space and identify the transitions among several chimera patterns, an in-phase synchronized state, and a global amplitude death state.

  17. Imperfect traveling chimera states induced by local synaptic gradient coupling.

    Bera, Bidesh K; Ghosh, Dibakar; Banerjee, Tanmoy

    2016-07-01

    In this paper, we report the occurrence of chimera patterns in a network of neuronal oscillators, which are coupled through local, synaptic gradient coupling. We discover a new chimera pattern, namely the imperfect traveling chimera state, where the incoherent traveling domain spreads into the coherent domain of the network. Remarkably, we also find that chimera states arise even for one-way local coupling, which is in contrast to the earlier belief that only nonlocal, global, or nearest-neighbor local coupling can give rise to chimera state; this find further relaxes the essential connectivity requirement of getting a chimera state. We choose a network of identical bursting Hindmarsh-Rose neuronal oscillators, and we show that depending upon the relative strength of the synaptic and gradient coupling, several chimera patterns emerge. We map all the spatiotemporal behaviors in parameter space and identify the transitions among several chimera patterns, an in-phase synchronized state, and a global amplitude death state. PMID:27575131

  18. Antibody responses in allogeneic radiation chimeras

    The construction of long-lived allogeneic radiation chimeras, free of graft-versus-host disease, has been achieved using serologic elimination of Thy 1+ cells from donor bone marrow. Humoral immune function was not restored in these animals as evidenced by lack of primary antibody responses to a T cell-dependent antigen, namely, sheep erythrocytes (SRBC) both in vivo and in vitro. No evidence for a suppressor cell-mediated mechanism was found. Using separated chimera spleen cell populations and specific helper cell soluble mediators, the functional capabilities of chimera B cells, T cells, and macrophages were assessed. These findings suggested that the failure of chimeras to produce antibody is not the result of impaired B cell, T cell, or macrophage function, but rather, that it is due to ineffective cellular interactions. Physiologic cellular interactions depend upon the sharing of major histocompatibility complex (MHC) determinants between interacting cells. However, the self-recognition repertoire of developing T cells may be influenced by the environment which these cells differentiate such that they learn to recognize host MHC determinants as self. These findings support the interpretation that the immunologic hyporeactivity of allogeneic bone marrow chimeras reflects the role of the host environment in restricting the interactive capabilities of donor-derived cells

  19. Persistent chimera states in nonlocally coupled phase oscillators

    Suda, Yusuke; Okuda, Koji

    2015-01-01

    Chimera states in the systems of nonlocally coupled phase oscillators are considered stable in the continuous limit of spatially distributed oscillators. However, it is reported that in the numerical simulations without taking such limit, chimera states are chaotic transient and finally collapse into the completely synchronous solution. In this paper, we numerically study chimera states by using the coupling function different from the previous studies and obtain the result that chimera state...

  20. Chimera states on the surface of a sphere

    Panaggio, Mark J; Abrams, Daniel M.

    2014-01-01

    A chimera state is a spatiotemporal pattern in which a network of identical coupled oscillators exhibits coexisting regions of asynchronous and synchronous oscillation. Two distinct classes of chimera states have been shown to exist: "spots" and "spirals." Here we study coupled oscillators on the surface of a sphere, a single system in which both spot and spiral chimera states appear. We present an analysis of the birth and death of spiral chimera states and show that although they coexist wi...

  1. Imperfect traveling chimera states induced by local synaptic gradient coupling

    Bera, Bidesh K.; Ghosh, Dibakar; Banerjee, Tanmoy

    2016-01-01

    In this paper we report the occurrence of chimera patterns in a network of neuronal oscillators, which are coupled through {\\it local}, synaptic {\\it gradient} coupling. We discover a new chimera pattern, namely the {\\it imperfect traveling chimera} where the incoherent traveling domain spreads into the coherent domain of the network. Remarkably, we also find that chimera states arise even for {\\it one-way} local coupling, which is in contrast to the earlier belief that only nonlocal, global ...

  2. Chimera states: The natural link between coherence and incoherence

    Omel'chenko, O.; Maistrenko, Yu.; Tass, P. A.

    2008-01-01

    Chimera states are remarkable spatiotemporal patterns in which coherence coexists with incoherence. As yet, chimera states have been considered as nongeneric, since they emerge only for particular initial conditions. In contrast, we show here that in a network of globally coupled oscillators delayed feedback stimulation with realistic (i.e., spatially decaying) stimulation profile generically induces chimera states. Intriguingly, a bifurcation analysis reveals that these chimera states are th...

  3. Turbulent chimeras in large semiconductor laser arrays

    Shena, Joniald; Kovanis, Vassilios; Tsironis, George P

    2016-01-01

    Semiconductor laser arrays have been investigated experimentally and theoretically from the viewpoint of temporal and spatial coherence for the past forty years. In this work, we are focusing on a rather novel complex collective behavior, namely chimera states, where synchronized clusters of emitters coexist with unsynchronized ones. For the first time, we find such states exist in large diode arrays based on quantum well gain media with nearest-neighbor interactions. The crucial parameters are the evanescent coupling strength and the relative optical frequency detuning between the emitters of the array. By employing a recently proposed figure of merit for classifying chimera states, we provide quantitative and qualitative evidence for the observed dynamics. The corresponding chimeras are identified as turbulent according to the irregular temporal behavior of the classification measure. Such studies may be the springboard for designing next generation photonic emitters providing on demand diverse waveforms.

  4. Basins of Attraction for Chimera States

    Martens, Erik Andreas; Panaggio, Mark; Abrams, Daniel

    2016-01-01

    Chimera states---curious symmetry-broken states in systems of identical coupled oscillators---typically occur only for certain initial conditions. Here we analyze their basins of attraction in a simple system comprised of two populations. Using perturbative analysis and numerical simulation we...... evaluate asymptotic states and associated destination maps, and demonstrate that basins form a complex twisting structure in phase space. Understanding the basins' precise nature may help in the development of control methods to switch between chimera patterns, with possible technological and neural system...

  5. Basins of attraction for chimera states

    Martens, Erik A.; Panaggio, Mark J.; Abrams, Daniel M.

    2016-02-01

    Chimera states—curious symmetry-broken states in systems of identical coupled oscillators—typically occur only for certain initial conditions. Here we analyze their basins of attraction in a simple system comprised of two populations. Using perturbative analysis and numerical simulation we evaluate asymptotic states and associated destination maps, and demonstrate that basins form a complex twisting structure in phase space. Understanding the basins’ precise nature may help in the development of control methods to switch between chimera patterns, with possible technological and neural system applications.

  6. Chimera states: limits and open questions

    Abrams, Daniel; Panaggio, Mark

    2015-03-01

    ``Chimera states'' are surprising patterns that can be found in systems of identical coupled oscillators, where synchrony and incoherence seem to stably coexist in a spatially asymmetrical state. The existence and stability of chimera states in a variety of settings relevant to real-world systems remains an active topic of research. Here I summarize what is known and present preliminary results for interesting limits including small and large-N, small and large coupling lag, as well as near-local and near-global coupling.

  7. α-Peptide/ß-Peptoid Chimeras

    Olsen, Christian Adam; Bonke, Gitte; Vedel, Line;

    2007-01-01

    We describe the synthesis and characterization of the first generation of oligomers consisting of alternating repeats of a-amino acids and chiral N-alkyl-ß-alanine (ß-peptoid) residues. These chimeras are stable toward proteolysis, non-hemolytic, and possess antibacterial activity comparable to...... well-known antimicrobial agents. Moreover, the chimeras exhibit length-dependent, concentration-dependent, solvent-dependent, and ion-strength-dependent ellipticity, indicating the presence of a secondary structure in solution. Thus, a-peptide/ß-peptoid oligomers represent a promising novel...

  8. Chimera states in mechanical oscillator networks

    Martens, Erik Andreas; Thutupalli, Shashi; Fourrière, Antoine; Hallatschek, Oskar

    2013-01-01

    The synchronization of coupled oscillators is a fascinating manifestation of self-organization that nature uses to orchestrate essential processes of life, such as the beating of the heart. Although it was long thought that synchrony and disorder were mutually exclusive steady states for a network...... a hierarchical network to show that chimeras emerge naturally from a competition between two antagonistic synchronization patterns. We identify a wide spectrum of complex states, encompassing and extending the set of previously described chimeras. Our mathematical model shows that the self......, optomechanical crystals, or cells communicating via quorum sensing in microbial populations...

  9. Persistent chimera states in nonlocally coupled phase oscillators

    Suda, Yusuke; Okuda, Koji

    2015-12-01

    Chimera states in the systems of nonlocally coupled phase oscillators are considered stable in the continuous limit of spatially distributed oscillators. However, it is reported that in the numerical simulations without taking such limit, chimera states are chaotic transient and finally collapse into the completely synchronous solution. In this Rapid Communication, we numerically study chimera states by using the coupling function different from the previous studies and obtain the result that chimera states can be stable even without taking the continuous limit, which we call the persistent chimera state.

  10. Bistable Chimera Attractors on a Triangular Network of Oscillator Populations

    Martens, Erik Andreas

    2010-01-01

    . This triangular network is the simplest discretization of a continuous ring of oscillators. Yet it displays an unexpectedly different behavior: in contrast to the lone stable chimera observed in continuous rings of oscillators, we find that this system exhibits two coexisting stable chimeras. Both...... chimeras are, as usual, born through a saddle-node bifurcation. As the coupling becomes increasingly local in nature they lose stability through a Hopf bifurcation, giving rise to breathing chimeras, which in turn get destroyed through a homoclinic bifurcation. Remarkably, one of the chimeras reemerges by...

  11. The C5a receptor impairs IL-12–dependent clearance of Porphyromonas gingivalis and is required for induction of periodontal bone loss1

    Liang, Shuang; Krauss, Jennifer L.; Domon, Hisanori; McIntosh, Megan L.; Hosur, Kavita B.; Qu, Hongchang; Li, Fenge; Tzekou, Apostolia; Lambris, John D.; Hajishengallis, George

    2010-01-01

    The C5a anaphylatoxin receptor (C5aR; CD88) is activated as part of the complement cascade and exerts important inflammatory, antimicrobial and regulatory functions, at least in part, via crosstalk with TLRs. However, the periodontal pathogen Porphyromonas gingivalis can control C5aR activation by generating C5a through its own C5 convertase-like enzymatic activity. Here we show that P. gingivalis uses this mechanism to proactively and selectively inhibit TLR2-induced IL-12p70, whereas the sa...

  12. The effects of a 5-HT5A receptor antagonist in a ketamine-based rat model of cognitive dysfunction and the negative symptoms of schizophrenia.

    Nikiforuk, Agnieszka; Hołuj, Małgorzata; Kos, Tomasz; Popik, Piotr

    2016-06-01

    Serotonin (5-HT) receptors still represent promising targets for the development of novel multireceptor or stand-alone antipsychotic drugs with a potential to ameliorate cognitive impairments and negative symptoms in schizophrenia. The 5-HT5A receptor, one of the least known members of the serotonin receptor family, has also drawn attention in this regard. Although the antipsychotic efficacy of 5-HT5A antagonists is still equivocal, recent experimental data suggest the cognitive-enhancing activity of this strategy. The aim of the present study was to evaluate pro-cognitive and pro-social efficacies of the 5-HT5A receptor antagonist in a rat pharmacological model of schizophrenia employing the administration of the NMDA receptor antagonist, ketamine. The ability of SB-699551 to reverse ketamine-induced cognitive deficits in the attentional set-shifting task (ASST) and novel object recognition task (NORT) was examined. The compound's efficacy against ketamine-induced social withdrawal was assessed in the social interaction test (SIT) and in the social choice test (SCT). The results demonstrated the efficacy of SB-699551 in ameliorating ketamine-induced impairments on the ASST and NORT. Moreover, the tested compound also enhanced set-shifting performance in cognitively unimpaired control rats and improved object recognition memory in conditions of delay-induced natural forgetting. The pro-social activity of SB-699551 was demonstrated on both employed paradigms, the SIT and SCT. The present study suggests the preclinical efficacy of a strategy based on the blockade of 5-HT5A receptors against schizophrenia-like cognitive deficits and negative symptoms. The utility of this receptor as a target for improvement of cognitive and social dysfunctions warrants further studies. PMID:26826431

  13. Basins of Attraction for Chimera States

    Martens, Erik Andreas; Panaggio, Mark; Abrams, Daniel

    2016-01-01

    Chimera states---curious symmetry-broken states in systems of identical coupled oscillators---typically occur only for certain initial conditions. Here we analyze their basins of attraction in a simple system comprised of two populations. Using perturbative analysis and numerical simulation we...

  14. CHIMERA Multidetector at Laboratori Nazionali del Sud

    The installation of CHIMERA multidetector, designed in order to study central collisions in heavy ion reactions at intermediate energy, is going on at LNS and the first experiment with the forward part (688 telescopes) is running since May 1999. The aim of this contribution is to present the status of the project

  15. Local complement-targeted intervention in periodontitis: proof-of-concept using a C5a receptor (CD88) antagonist1

    Abe, Toshiharu; Hosur, Kavita B.; Hajishengallis, Evlambia; Reis, Edimara S.; Ricklin, Daniel; Lambris, John D.; Hajishengallis, George

    2012-01-01

    When excessively activated or deregulated, complement becomes a major link between infection and inflammatory pathology including periodontitis. This oral inflammatory disease is associated with a dysbiotic microbiota, leads to the destruction of bone and other tooth-supporting structures, and exerts an adverse impact on systemic health. We have previously shown that mice deficient either in complement C5a receptor (C5aR; CD88) or TLR2 are highly and similarly resistant to periodontitis, sugg...

  16. Role of 5-HT5A and 5-HT1B/1D receptors in the antinociception produced by ergotamine and valerenic acid in the rat formalin test.

    Vidal-Cantú, Guadalupe C; Jiménez-Hernández, Mildred; Rocha-González, Héctor I; Villalón, Carlos M; Granados-Soto, Vinicio; Muñoz-Islas, Enriqueta

    2016-06-15

    Sumatriptan, dihydroergotamine and methysergide inhibit 1% formalin-induced nociception by activation of peripheral 5-HT1B/1D receptors. This study set out to investigate the pharmacological profile of the antinociception produced by intrathecal and intraplantar administration of ergotamine (a 5-HT1B/1D and 5-HT5A/5B receptor agonist) and valerenic acid (a partial agonist at 5-HT5A receptors). Intraplantar injection of 1% formalin in the right hind paw resulted in spontaneous flinching behavior of the injected hindpaw of female Wistar rats. Intrathecal ergotamine (15nmol) or valerenic acid (1 nmol) blocked in a dose dependent manner formalin-induced nociception. The antinociception by intrathecal ergotamine (15nmol) or valerenic acid (1nmol) was partly or completely blocked by intrathecal administration of the antagonists: (i) methiothepin (non-selective 5-HT5A/5B; 0.01-0.1nmol); (ii) SB-699551 (selective 5-HT5A; up to 10nmol); (iii) anti-5-HT5A antibody; (iv) SB-224289 (selective 5-HT1B; 0.1-1nmol); or (v) BRL-15572 (selective 5-HT1D; 0.1-1nmol). Likewise, antinociception by intraplantar ergotamine (15nmol) and valerenic acid (10nmol) was: (i) partially blocked by methiothepin (1nmol), SB-699551 (10nmol) or SB-224289 (1nmol); and (ii) abolished by BRL-15572 (1nmol). The above doses of antagonists (which did not affect per se the formalin-induced nociception) were high enough to completely block their respective receptors. Our results suggest that ergotamine and valerenic acid produce antinociception via 5-HT5A and 5-HT1B/1D receptors located at both spinal and peripheral sites. This provides new evidence for understanding the modulation of nociceptive pathways in inflammatory pain. PMID:27068146

  17. Expression of complement C5a receptor and the viability of 4T1 tumor cells following agonist–antagonist treatment

    Nurneqman Nashreq Kosni

    2016-01-01

    Conclusion: This experiment shows the presence of C5a receptor on 4T1 cell line. We believe that the antagonist peptide is eligible to be used widely in cancer immunotherapy field; but in vivo studies need to be carried out first in the future, as it will determine how these drugs affect the tumor cell growth.

  18. Differentiation-specific action of orphan nuclear receptor NR5A1 (SF-1): transcriptional regulation in luteinizing bovine theca cells

    Walther, Norbert; Jansen, Martina; Akbary, Wasima; Ivell, Richard

    2006-01-01

    Background The orphan nuclear receptor NR5A1 (steroidogenic factor-1, SF-1) is a master regulator of tissue-specific gene expression in reproductive and steroidogenic tissues. Two activating functions, AF-1 and AF-2, have been described to function in a cooperative manner to recruit transcriptional coactivators to the promoter regions of NR5A1-controlled genes. Methods The role of the NR5A1 activating functions AF-1 and AF-2 was studied in primary bovine theca cells. Bovine theca cells were i...

  19. Clustered chimera states in systems of type-I excitability

    The chimera state is a fascinating phenomenon of coexisting synchronized and desynchronized behaviour that was discovered in networks of nonlocally coupled identical phase oscillators over ten years ago. Since then, chimeras have been found in numerous theoretical and experimental studies and more recently in models of neuronal dynamics as well. In this work, we consider a generic model for a saddle-node bifurcation on a limit cycle representative of neural excitability type I. We obtain chimera states with multiple coherent regions (clustered chimeras/multi-chimeras) depending on the distance from the excitability threshold, the range of nonlocal coupling and the coupling strength. A detailed stability diagram for these chimera states and other interesting coexisting patterns (like traveling waves) is presented. (paper)

  20. Preliminary results of Digital Pulse Shape Acquisition from Chimera

    Alderighi, D.M.; Sechi, G. [INFN Milano and IASF, CNR, Milano (France); Anzalone, A.; Cavallaro, S.; Giustolisi, F.; Laguidara, E.; Lanzalone, G.; Porto, F. [Catania Univ., LNS and Dipartimento di Fisica (France); Bassini, R.; Boiano, C.; Guazzoni, P.; Russo, S.; Sassi, M.; Zetta, L. [Milano Univ., INFN and Dipartimento di Fisica (Italy); Cardella, G.; Defilippo, S.E.; Lanzano, G.; Paganod, A.; Papa, M.; Pirrone, S.; Politi, G. [Catania Univ., INFN and Dipartimento di Fisica (Italy); Geraci, E. [Bologna Univ., INFN and Dipartimento di Fisica (Italy)

    2003-07-01

    A 100 MS/s 14-bit Sampling Analog-to-Digital converter has been used to perform digital pulse-shape acquisition of signals collected from CHIMERA telescopes. The signals from a typical CHIMERA detection cell have been collected using both a standard CHIMERA electronic chain up to the amplifier, and a very simple analog front end, basically reduced to the preamplifier. The preliminary on-beam results are presented. (authors)

  1. Preliminary results of Digital Pulse Shape Acquisition from Chimera

    A 100 MS/s 14-bit Sampling Analog-to-Digital converter has been used to perform digital pulse-shape acquisition of signals collected from CHIMERA telescopes. The signals from a typical CHIMERA detection cell have been collected using both a standard CHIMERA electronic chain up to the amplifier, and a very simple analog front end, basically reduced to the preamplifier. The preliminary on-beam results are presented. (authors)

  2. Chimera states in hierarchical networks of Van der Pol oscillators

    Ulonska, Stefan; Omelchenko, Iryna; Zakharova, Anna; Schoell, Eckehard

    2016-01-01

    Chimera states are complex spatio-temporal patterns that consist of coexisting domains of coherent and incoherent dynamics. We analyse chimera states in networks of Van der Pol oscillators with hierarchical coupling topology. We investigate the stepwise transition from a nonlocal to a hierarchical topology, and propose the network clustering coefficient as a measure to establish a link between the existence of chimera states and the compactness of the initial base pattern of a hierarchical to...

  3. Weak chimeras in minimal networks of coupled phase oscillators

    Ashwin, Peter; Burylko, Oleksandr

    2014-01-01

    We suggest a definition for a type of chimera state that appears in networks of indistinguishable phase oscillators. Defining a "weak chimera" as a type of invariant set showing partial frequency synchronization, we show that this means they cannot appear in phase oscillator networks that are either globally coupled or too small. We exhibit various networks of four, six and ten indistinguishable oscillators where weak chimeras exist with various dynamics and stabilities. We examine the role o...

  4. Chimera Ising Walls in Forced Nonlocally Coupled Oscillators

    Kawamura, Yoji

    2007-01-01

    Nonlocally coupled oscillator systems can exhibit an exotic spatiotemporal structure called chimera, where the system splits into two groups of oscillators with sharp boundaries, one of which is phase-locked and the other is phase-randomized. Two examples of the chimera states are known: the first one appears in a ring of phase oscillators, and the second one is associated with the two-dimensional rotating spiral waves. In this article, we report yet another example of the chimera state that ...

  5. Self-Emerging and Turbulent Chimeras in Oscillator Chains

    Bordyugov, G.; Pikovsky, A.; Rosenblum, M.

    2010-01-01

    We report on a self-emerging chimera state in a homogeneous chain of nonlocally and nonlinearly coupled oscillators. This chimera, i.e. a state with coexisting regions of complete and partial synchrony, emerges via a supercritical bifurcation from a homogeneous state and thus does not require preparation of special initial conditions. We develop a theory of chimera basing on the equations for the local complex order parameter in the Ott-Antonsen approximation. Applying a numerical linear stab...

  6. Nonspecific suppressor elements in murine allogeneic radiation chimeras

    Spleen cells from long-term mouse allogeneic radiation chimeras were tested for their ability to modulate the graft-versus-host (GVH) or plaque-forming cell (PFC) response of normal lymphocytes transplanted in lethally x-irradiated recipients. In vivo GVH proliferation of normal lymphocytes (syngeneic to donor cells of the chimera) against antigens of host-type in which the chimeric state had been established was reduced by chimera cells. Inhibition varied, some chimeras suppressing GVH more than others and a few not suppressing at all. The suppressive effect was abrogated if the chimera cells were treated with anti-THETA; treatment with anti-IgM did not eliminate this activity. When mixtures of normal donor lymphocytes and chimera cells were given to irradiated recipients genetically different from host or donor, reduction of donor cell GVH also occurred. Further, chimera cells reduced the GVH activity of normal host cells in irradiated recipients differing from the host at one H-2 locus and from the donor at minor histocompatibility loci. The modulating effect of spleen cells from chimeras on the PFC response by normal lymphocytes also varied. Six chimeras induced a 25 to 90% suppression, two enhanced the response, and one showed no effect. Where suppression occurred, treatment of chimera cells with anti-THETA most often, but not always, restored PFC production. Our results show that the suppressive action of splenic lymphoid cells by chimeras is highly nonspecific and variable in expression. We suggest that tolerance in chimeras may be mediated by nonspecific suppressor elements leading to unresponsiveness to a variety of antigens including SRBC

  7. Chimera: a Bioconductor package for secondary analysis of fusion products.

    Beccuti, Marco; Carrara, Matteo; Cordero, Francesca; Lazzarato, Fulvio; Donatelli, Susanna; Nadalin, Francesca; Policriti, Alberto; Calogero, Raffaele A.

    2014-01-01

    Summary: Chimera is a Bioconductor package that organizes, annotates, analyses and validates fusions reported by different fusion detection tools; current implementation can deal with output from bellerophontes, chimeraScan, deFuse, fusionCatcher, FusionFinder, FusionHunter, FusionMap, mapSplice, Rsubread, tophat-fusion and STAR. The core of Chimera is a fusion data structure that can store fusion events detected with any of the aforementioned tools. Fusions are then easily manipulated with s...

  8. Clustered Chimera States in Systems of Type-I Excitability

    Vüllings, Andrea; Hizanidis, Johanne; Omelchenko, Iryna; Hövel, Philipp

    2014-01-01

    Chimera is a fascinating phenomenon of coexisting synchronized and desynchronized behaviour that was discovered in networks of nonlocally coupled identical phase oscillators over ten years ago. Since then, chimeras were found in numerous theoretical and experimental studies and more recently in models of neuronal dynamics as well. In this work, we consider a generic model for a saddle-node bifurcation on a limit cycle representative for neural excitability type I. We obtain chimera states wit...

  9. Intermittent chaotic chimeras for coupled rotators

    Olmi, Simona; Martens, Erik Andreas; Thutupalli, Shashi; Torcini, Alessandro

    2015-01-01

    wo symmetrically coupled populations of N oscillators with inertia m display chaotic solutions with broken symmetry similar to experimental observations with mechanical pendulums. In particular, we report evidence of intermittent chaotic chimeras, where one population is synchronized and the othe...... jumps erratically between laminar and turbulent phases. These states have finite lifetimes diverging as a power law with N and m. Lyapunov analyses reveal chaotic properties in quantitative agreement with theoretical predictions for globally coupled dissipative systems....

  10. Chimera states: The Existence Criteria Revisited

    Sethia, Gautam C.; Sen, Abhijit

    2013-01-01

    Chimera states, representing a spontaneous break-up of a population of identical oscillators that are identically coupled, into sub-populations displaying synchronized and desynchronized behavior, have traditionally been found to exist in weakly coupled systems and with some form of nonlocal coupling between the oscillators. Here we show that neither the weak-coupling approximation nor nonlocal coupling are essential conditions for their existence. We obtain for the first time amplitude-media...

  11. Nucleic acid visualization with UCSF Chimera

    Couch, Gregory S.; Hendrix, Donna K.; Ferrin, Thomas E.

    2006-01-01

    With the increase in the number of large, 3D, high-resolution nucleic acid structures, particularly of the 30S and 50S ribosomal subunits and the intact bacterial ribosome, advancements in the visualization of nucleic acid structural features are essential. Large molecular structures are complicated and detailed, and one goal of visualization software is to allow the user to simplify the display of some features and accent others. We describe an extension to the UCSF Chimera molecular visuali...

  12. Computing Flows Using Chimera and Unstructured Grids

    Liou, Meng-Sing; Zheng, Yao

    2006-01-01

    DRAGONFLOW is a computer program that solves the Navier-Stokes equations of flows in complexly shaped three-dimensional regions discretized by use of a direct replacement of arbitrary grid overlapping by nonstructured (DRAGON) grid. A DRAGON grid (see figure) is a combination of a chimera grid (a composite of structured subgrids) and a collection of unstructured subgrids. DRAGONFLOW incorporates modified versions of two prior Navier-Stokes-equation-solving programs: OVERFLOW, which is designed to solve on chimera grids; and USM3D, which is used to solve on unstructured grids. A master module controls the invocation of individual modules in the libraries. At each time step of a simulated flow, DRAGONFLOW is invoked on the chimera portion of the DRAGON grid in alternation with USM3D, which is invoked on the unstructured subgrids of the DRAGON grid. The USM3D and OVERFLOW modules then immediately exchange their solutions and other data. As a result, USM3D and OVERFLOW are coupled seamlessly.

  13. Evoluce Toll-like receptorů 4, 5 a 7 u ptáků ze skupiny Galloanserae

    Vinkler, M.; Bainová, H.; Bryja, Josef

    Brno: Ústav biologie obratlovců AV ČR, 2015 - (Bryja, J.; Řehák, Z.; Zukal, J.). s. 254-255 ISBN 978-80-87189-18-4. [Zoologické dny. 12.02.2015-13.02.2015, Brno] Institutional support: RVO:68081766 Keywords : Toll-like receptors * birds Subject RIV: EG - Zoology

  14. A New Approximate Chimera Donor Cell Search Algorithm

    Holst, Terry L.; Nixon, David (Technical Monitor)

    1998-01-01

    The objectives of this study were to develop chimera-based full potential methodology which is compatible with overflow (Euler/Navier-Stokes) chimera flow solver and to develop a fast donor cell search algorithm that is compatible with the chimera full potential approach. Results of this work included presenting a new donor cell search algorithm suitable for use with a chimera-based full potential solver. This algorithm was found to be extremely fast and simple producing donor cells as fast as 60,000 per second.

  15. Chimera states in spatiotemporal systems: Theory and Applications

    Yao, Nan; Zheng, Zhigang

    2016-03-01

    In this paper, we propose a retrospective and summary on recent studies of chimera states. Chimera states demonstrate striking inhomogeneous spatiotemporal patterns emerging in homogeneous systems through unexpected spontaneous symmetry breaking, where the consequent spatiotemporal patterns are composed of both coherence and incoherence domains, respectively characterized by the synchronized and desynchronized motions of oscillators. Since the discovery of chimera states by Kuramoto and others, this striking collective behavior has attracted a great deal of research interest in the community of physics and related interdisciplinary fields from both theoretical and experimental viewpoints. In recent works exploring chimera states, rich phenomena such as the spiral wave chimera, multiple cluster chimera, amplitude chimera were observed from various types of model systems. Theoretical framework by means of self-consistency approach and Ott-Antonsen approach were proposed for further understanding to this symmetry-breaking-induced behavior. The stability and robustness of chimera states were also discussed. More importantly, experiments ranging from optical, chemical to mechanical designs successfully approve the existence of chimera states.

  16. Coherence-Resonance Chimeras in a Network of Excitable Elements

    Semenova, Nadezhda; Zakharova, Anna; Anishchenko, Vadim; Schöll, Eckehard

    2016-07-01

    We demonstrate that chimera behavior can be observed in nonlocally coupled networks of excitable systems in the presence of noise. This phenomenon is distinct from classical chimeras, which occur in deterministic oscillatory systems, and it combines temporal features of coherence resonance, i.e., the constructive role of noise, and spatial properties of chimera states, i.e., the coexistence of spatially coherent and incoherent domains in a network of identical elements. Coherence-resonance chimeras are associated with alternating switching of the location of coherent and incoherent domains, which might be relevant in neuronal networks.

  17. Crystallization and X-ray diffraction analysis of human CLEC5A (MDL-1), a dengue virus receptor

    Recombinant human CLEC5A was crystallized in the trigonal space group P31 and X-ray diffraction data were collected to 1.56 Å resolution. The human C-type lectin-like protein CLEC5A (also known as MDL-1) is expressed on the surface of myeloid cells and plays a critical role in dengue-virus-induced disease by signalling through the transmembrane adaptor protein DAP12. The C-type lectin-like domain of CLEC5A was expressed in Escherichia coli, refolded and purified. Recombinant CLEC5A crystals were grown by sitting-drop vapour diffusion using polyethylene glycol 6000 as a precipitant. After optimization, crystals were grown which diffracted to 1.56 Å using synchrotron radiation. The results presented in this paper suggest that crystals producing diffraction of this quality will be suitable for structural determination of human CLEC5A

  18. TRPM5, a taste-signaling transient receptor potential ion-channel, is a ubiquitous signaling component in chemosensory cells

    Hofmann Thomas

    2007-07-01

    Full Text Available Abstract Background A growing number of TRP channels have been identified as key players in the sensation of smell, temperature, mechanical forces and taste. TRPM5 is known to be abundantly expressed in taste receptor cells where it participates in sweet, amino acid and bitter perception. A role of TRPM5 in other sensory systems, however, has not been studied so far. Results Here, we systematically investigated the expression of TRPM5 in rat and mouse tissues. Apart from taste buds, where we found TRPM5 to be predominantly localized on the basolateral surface of taste receptor cells, TRPM5 immunoreactivity was seen in other chemosensory organs – the main olfactory epithelium and the vomeronasal organ. Most strikingly, we found solitary TRPM5-enriched epithelial cells in all parts of the respiratory and gastrointestinal tract. Based on their tissue distribution, the low cell density, morphological features and co-immunostaining with different epithelial markers, we identified these cells as brush cells (also known as tuft, fibrillovesicular, multivesicular or caveolated cells. In terms of morphological characteristics, brush cells resemble taste receptor cells, while their origin and biological role are still under intensive debate. Conclusion We consider TRPM5 to be an intrinsic signaling component of mammalian chemosensory organs, and provide evidence for brush cells being an important cellular correlate in the periphery.

  19. The complement receptor C5aR1 contributes to renal damage but protects the heart in angiotensin II-induced hypertension.

    Weiss, Sebastian; Rosendahl, Alva; Czesla, Daniel; Meyer-Schwesinger, Catherine; Stahl, Rolf A K; Ehmke, Heimo; Kurts, Christian; Zipfel, Peter F; Köhl, Jörg; Wenzel, Ulrich O

    2016-06-01

    Adaptive and innate immune responses contribute to hypertension and hypertensive end-organ damage. Here, we determined the role of anaphylatoxin C5a, a major inflammatory effector of the innate immune system that is generated in response to complement activation, in hypertensive end-organ damage. For this purpose, we assessed the phenotype of C5a receptor 1 (C5aR1)-deficient mice in ANG II-induced renal and cardiac injury. Expression of C5aR1 on infiltrating and resident renal as well as cardiac cells was determined using a green fluorescent protein (GFP)-C5aR1 reporter knockin mouse. Flow cytometric analysis of leukocytes isolated from the kidney of GFP-C5aR1 reporter mice showed that 28% of CD45-positive cells expressed C5aR1. Dendritic cells were identified as the major C5aR1-expressing population (88.5%) followed by macrophages and neutrophils. Using confocal microscopy, we detected C5aR1 in the kidney mainly on infiltrating cells. In the heart, only infiltrating cells stained C5aR1 positive. To evaluate the role of C5aR1 deficiency in hypertensive injury, an aggravated model of hypertension was used. Unilateral nephrectomy was performed followed by infusion of ANG II (1.5 ng·g(-1)·min(-1)) and salt in wild-type (n = 34) and C5aR1-deficient mice (n = 32). C5aR1-deficient mice exhibited less renal injury, as evidenced by significantly reduced albuminuria. In contrast, cardiac injury was accelerated with significantly increased cardiac fibrosis and heart weight in C5aR1-deficient mice after ANG II infusion. No effect was found on blood pressure. In summary, the C5a:C5aR1 axis drives end-organ damage in the kidney but protects from the development of cardiac fibrosis and hypertrophy in experimental ANG II-induced hypertension. PMID:27053686

  20. Mean-field-diffusion-induced chimera death state

    Banerjee, Tanmoy

    2015-06-01

    Recently a novel dynamical state, called the chimera death, has been discovered in a network of nonlocally coupled identical oscillators (Zakharova A., Kapeller M. and Schöll E., Phys. Rev. Lett., 112 (2014) 154101), which is defined as the coexistence of spatially coherent and incoherent oscillation death state. This state arises due to the interplay of nonlocality and symmetry breaking and thus it bridges the gap between two important dynamical states, namely the chimera and oscillation death. In this paper we show that the chimera death can be induced in a network of generic identical oscillators with mean-field diffusive coupling and thus we establish that a nonlocal coupling is not essential to obtain chimera death. We identify a new transition route to the chimera death state, namely the transition from in-phase synchronized oscillation to chimera death via global amplitude death state. We ascribe the occurrence of chimera death to the bifurcation structure of the network in the limiting condition and show that multi-cluster chimera death states can be achieved by a proper choice of initial conditions.

  1. Biophysical and structural investigation of bacterially expressed and engineered CCR5, a G protein-coupled receptor

    The chemokine receptor CCR5 belongs to the class of G protein-coupled receptors. Besides its role in leukocyte trafficking, it is also the major HIV-1 coreceptor and hence a target for HIV-1 entry inhibitors. Here, we report Escherichia coli expression and a broad range of biophysical studies on E. coli-produced CCR5. After systematic screening and optimization, we obtained 10 mg of purified, detergent-solubilized, folded CCR5 from 1L culture in a triply isotope-labeled (2H/15N/13C) minimal medium. Thus the material is suitable for NMR spectroscopic studies. The expected α-helical secondary structure content is confirmed by circular dichroism spectroscopy. The solubilized CCR5 is monodisperse and homogeneous as judged by transmission electron microscopy. Interactions of CCR5 with its ligands, RANTES and MIP-1β were assessed by surface plasmon resonance yielding KD values in the nanomolar range. Using size exclusion chromatography, stable monomeric CCR5 could be isolated. We show that cysteine residues affect both the yield and oligomer distribution of CCR5. HSQC spectra suggest that the transmembrane domains of CCR5 are in equilibrium between several conformations. In addition we present a model of CCR5 based on the crystal structure of CXCR4 as a starting point for protein engineering.

  2. Biophysical and structural investigation of bacterially expressed and engineered CCR5, a G protein-coupled receptor

    Wiktor, Maciej; Morin, Sebastien; Sass, Hans-Juergen [University of Basel, Focal Area Structural Biology and Biophysics, Biozentrum (Switzerland); Kebbel, Fabian [University of Basel, Center for Cellular Imaging and NanoAnalytics (C-CINA), Biozentrum (Switzerland); Grzesiek, Stephan, E-mail: stephan.grzesiek@unibas.ch [University of Basel, Focal Area Structural Biology and Biophysics, Biozentrum (Switzerland)

    2013-01-15

    The chemokine receptor CCR5 belongs to the class of G protein-coupled receptors. Besides its role in leukocyte trafficking, it is also the major HIV-1 coreceptor and hence a target for HIV-1 entry inhibitors. Here, we report Escherichia coli expression and a broad range of biophysical studies on E. coli-produced CCR5. After systematic screening and optimization, we obtained 10 mg of purified, detergent-solubilized, folded CCR5 from 1L culture in a triply isotope-labeled ({sup 2}H/{sup 15}N/{sup 13}C) minimal medium. Thus the material is suitable for NMR spectroscopic studies. The expected {alpha}-helical secondary structure content is confirmed by circular dichroism spectroscopy. The solubilized CCR5 is monodisperse and homogeneous as judged by transmission electron microscopy. Interactions of CCR5 with its ligands, RANTES and MIP-1{beta} were assessed by surface plasmon resonance yielding K{sub D} values in the nanomolar range. Using size exclusion chromatography, stable monomeric CCR5 could be isolated. We show that cysteine residues affect both the yield and oligomer distribution of CCR5. HSQC spectra suggest that the transmembrane domains of CCR5 are in equilibrium between several conformations. In addition we present a model of CCR5 based on the crystal structure of CXCR4 as a starting point for protein engineering.

  3. Implementing real-time robotic systems using CHIMERA II

    Stewart, David B.; Schmitz, Donald E.; Khosla, Pradeep K.

    1990-01-01

    A description is given of the CHIMERA II programming environment and operating system, which was developed for implementing real-time robotic systems. Sensor-based robotic systems contain both general- and special-purpose hardware, and thus the development of applications tends to be a time-consuming task. The CHIMERA II environment is designed to reduce the development time by providing a convenient software interface between the hardware and the user. CHIMERA II supports flexible hardware configurations which are based on one or more VME-backplanes. All communication across multiple processors is transparent to the user through an extensive set of interprocessor communication primitives. CHIMERA II also provides a high-performance real-time kernel which supports both deadline and highest-priority-first scheduling. The flexibility of CHIMERA II allows hierarchical models for robot control, such as NASREM, to be implemented with minimal programming time and effort.

  4. Spiral wave chimeras in locally coupled oscillator systems

    Li, Bing-Wei; Dierckx, Hans

    2016-02-01

    The recently discovered chimera state involves the coexistence of synchronized and desynchronized states for a group of identical oscillators. In this work, we show the existence of (inwardly) rotating spiral wave chimeras in the three-component reaction-diffusion systems where each element is locally coupled by diffusion. A transition from spiral waves with the smooth core to spiral wave chimeras is found as we change the local dynamics of the system or as we gradually increase the diffusion coefficient of the activator. Our findings on the spiral wave chimera in the reaction-diffusion systems suggest that spiral chimera states may be found in chemical and biological systems that can be modeled by a large population of oscillators indirectly coupled via a diffusive environment.

  5. Solvable Model of Spiral Wave Chimeras

    Martens, Erik Andreas; Laing, Carlo R.; Strogatz, Steven H.

    2010-01-01

    Spiral waves are ubiquitous in two-dimensional systems of chemical or biological oscillators coupled locally by diffusion. At the center of such spirals is a phase singularity, a topological defect where the oscillator amplitude drops to zero. But if the coupling is nonlocal, a new kind of spiral...... can occur, with a circular core consisting of desynchronized oscillators running at full amplitude. Here, we provide the first analytical description of such a spiral wave chimera and use perturbation theory to calculate its rotation speed and the size of its incoherent core....

  6. A 3-D chimera grid embedding technique

    Benek, J. A.; Buning, P. G.; Steger, J. L.

    1985-01-01

    A three-dimensional (3-D) chimera grid-embedding technique is described. The technique simplifies the construction of computational grids about complex geometries. The method subdivides the physical domain into regions which can accommodate easily generated grids. Communication among the grids is accomplished by interpolation of the dependent variables at grid boundaries. The procedures for constructing the composite mesh and the associated data structures are described. The method is demonstrated by solution of the Euler equations for the transonic flow about a wing/body, wing/body/tail, and a configuration of three ellipsoidal bodies.

  7. Chimera states in mechanical oscillator networks

    Martens, Erik Andreas; Thutupalli, Shashi; Fourrière, Antoine;

    2013-01-01

    of identical oscillators, numerous theoretical studies in recent years have revealed the intriguing possibility of "chimera states," in which the symmetry of the oscillator population is broken into a synchronous part and an asynchronous part. However, a striking lack of empirical evidence raises the question...... in our experiments is controlled by elementary dynamical equations from mechanics that are ubiquitous in many natural and technological systems. The symmetry-breaking mechanism revealed by our experiments may thus be prevalent in systems exhibiting collective behavior, such as power grids, optomechanical...... crystals, or cells communicating via quorum sensing in microbial populations...

  8. Regulation of C. elegans fat uptake and storage by acyl-CoA synthase-3 is dependent on NR5A family nuclear hormone receptor nhr-25

    Mullaney, Brendan C; Blind, Raymond D; Lemieux, George A;

    2010-01-01

    Acyl-CoA synthases are important for lipid synthesis and breakdown, generation of signaling molecules, and lipid modification of proteins, highlighting the challenge of understanding metabolic pathways within intact organisms. From a C. elegans mutagenesis screen, we found that loss of ACS-3, a l...... program of lipid uptake and synthesis. These results reveal a link between acyl-CoA synthase function and an NR5A family nuclear receptor in C. elegans....... mutant phenotypes require the nuclear hormone receptor NHR-25, a key regulator of C. elegans molting. Our findings suggest that ACS-3-derived long-chain fatty acyl-CoAs, perhaps incorporated into complex ligands such as phosphoinositides, modulate NHR-25 function, which in turn regulates an endocrine...

  9. 77 FR 65602 - Chimera Energy Corporation; Order of Suspension of Trading

    2012-10-29

    ... COMMISSION Chimera Energy Corporation; Order of Suspension of Trading October 25, 2012. It appears to the... securities of Chimera Energy Corporation (``Chimera'') because of questions regarding the accuracy of statements by Chimera in press releases to investors concerning, among other things, the company's...

  10. Immunologic studies of canine bone marrow chimeras

    When prospective male or female recipients from the Cooperstown colony were exposed to supralethal total body irradiation and were reconstituted with bone marrow obtained from genotypically DL-A-identical littermate or nonlittermate donors such treatment resulted, in regularly reproducible fashion, in the establishment of a long-term state of chimerism with no evidence of graft-versus-host disease in any of the recipients. The resulting chimeras have survived thus far for 882-1466 days, with donor red cell antigen and leukocyte sex marker evidence of the persistence of chimerism. Subsequent challenge of the chimeras with renal and skin allografts obtained from the specific donor of marrow resulted in the long-term survival of such transplants without any evidence of rejection for 833--1402 days. Skin allografts obtained from other dogs were, however, accorded first-set rejection times. Recent studies indicate that the state of allogeneic unresponsiveness produced by supralethal total body irradiation and bone marrow transplantation also extends to other organs from the donor of marrow, including heart, liver, pancreas and duodenum, and lung

  11. Chimera states in purely local delay-coupled oscillators

    Bera, Bidesh K.; Ghosh, Dibakar

    2016-05-01

    We study the existence of chimera states in a network of locally coupled chaotic and limit-cycle oscillators. The necessary condition for chimera state in purely local coupled oscillators is discussed. At first, we numerically observe the existence of chimera or multichimera states in the locally coupled Hindmarsh-Rose neuron model. We find that delay time in the nonlinear local coupling reduces the domain of the coherent island in the parameter space of the synaptic coupling strength and time delay, and thus the coherent region can be completely eliminated once the time delay exceeds a certain threshold. We then consider another form of nonlinearity in the local coupling, and the existence of chimera states is observed in the time-delayed Mackey-Glass system and in a Van der Pol oscillator. We also discuss the effect of time delay in local coupling for the existence of chimera states in Mackey-Glass systems. The nonlinearity present in the coupling function plays a key role in the emergence of chimera or multichimera states. A phase diagram for the chimera state is identified over a wide parameter space.

  12. Different kinds of chimera death states in nonlocally coupled oscillators

    Premalatha, K.; Chandrasekar, V. K.; Senthilvelan, M.; Lakshmanan, M.

    2016-05-01

    We investigate the significance of nonisochronicity parameter in a network of nonlocally coupled Stuart-Landau oscillators with symmetry breaking form. We observe that the presence of nonisochronicity parameter leads to structural changes in the chimera death region while varying the strength of the interaction. This gives rise to the existence of different types of chimera death states such as multichimera death state, type I periodic chimera death (PCD) state, and type II periodic chimera death state. We also find that the number of periodic domains in both types of PCD states decreases exponentially with an increase of coupling range and obeys a power law under nonlocal coupling. Additionally, we also analyze the structural changes of chimera death states by reducing the system of dynamical equations to a phase model through the phase reduction. We also briefly study the role of nonisochronicity parameter on chimera states, where the existence of a multichimera state with respect to the coupling range is pointed out. Moreover, we also analyze the robustness of the chimera death state to perturbations in the natural frequencies of the oscillators.

  13. Progesterone downregulation of miR-141 contributes to expansion of stem-like breast cancer cells through maintenance of progesterone receptor and Stat5a.

    Finlay-Schultz, J; Cittelly, D M; Hendricks, P; Patel, P; Kabos, P; Jacobsen, B M; Richer, J K; Sartorius, C A

    2015-07-01

    Progesterone (P4) has emerged as an important hormone-regulating mammary stem cell (MaSC) populations. In breast cancer, P4 and synthetic analogs increase the number of stem-like cells within luminal estrogen receptor (ER)- and progesterone receptor (PR)-positive breast cancers. These cells gain expression of de-differentiated cell markers CD44 and cytokeratin 5 (CK5), lose luminal markers ER and PR, and are more therapy resistant. We previously described that P4 downregulation of microRNA (miR)-29a contributes to the expansion of CD44(high) and CK5(+) cells. Here we investigated P4 downregulation of miR-141, a member of the miR-200 family of tumor suppressors, in facilitating an increase in stem-like breast cancer cells. miR-141 was the sole member of the miR-200 family P4-downregulated at the mature miRNA level in luminal breast cancer cell lines. Stable inhibition of miR-141 alone increased the CD44(high) population, and potentiated P4-mediated increases in both CD44(high) and CK5(+) cells. Loss of miR-141 enhanced both mammosphere formation and tumor initiation. miR-141 directly targeted both PR and signal transducer and activator of transcription 5A (Stat5a), transcription factors important for MaSC expansion. miR-141 depletion increased PR protein levels, even in cell lines where PR expression is estrogen dependent. Stat5a suppression via small interfering RNA or a small-molecule inhibitor reduced the P4-dependent increase in CK5(+) and CD44(high) cells. These data support a mechanism by which P4-triggered loss of miR-141 facilitates breast cancer cell de-differentiation through deregulation of PR and Stat5a, two transcription factors important for controlling mammary cell fate. PMID:25241899

  14. Multi-headed chimera states in coupled pendula

    Jaros, P.; Borkowski, L.; Witkowski, B.; Czolczynski, K.; Kapitaniak, T.

    2015-07-01

    We discuss the occurrence of the chimera states in the network of coupled, excited by the clock's mechanisms pendula. We find the patterns of multi-headed chimera states in which pendula clustered in different heads behave differently (oscillate with different frequencies) and create different types of synchronous states (complete or phase synchronization). The mathematical model of the network shows that the observed chimera states are controlled by elementary dynamical equations derived from the Newton's laws that are ubiquitous in many physical and engineering systems.

  15. Fast clique minor generation in Chimera qubit connectivity graphs

    Boothby, Tomas; King, Andrew D.; Roy, Aidan

    2015-01-01

    The current generation of D-Wave quantum annealing processor is designed to minimize the energy of an Ising spin configuration whose pairwise interactions lie on the edges of a {\\em Chimera} graph $\\mathcal C_{M,N,L}$. In order to solve an Ising spin problem with arbitrary pairwise interaction structure, the corresponding graph must be minor-embedded into a Chimera graph. We define a combinatorial class of {\\em native clique minors} in Chimera graphs with vertex images of uniform, near minima...

  16. Chimera states in coupled sine-circle map lattices

    Nayak, Chitra R.; Gupte, Neelima

    2010-01-01

    Systems of coupled oscillators have been seen to exhibit chimera states, i.e. states where the system splits into two groups where one group is phase locked and the other is phase randomized. In this work, we report the existence of chimera states in a system of two interacting populations of sine circle maps. This system also exhibits the clustered chimera behavior seen earlier in delay coupled systems. Rich spatio-temporal behavior is seen in different regimes of the phase diagram.We carry ...

  17. Treatment with the C5a receptor/CD88 antagonist PMX205 reduces inflammation in a murine model of allergic asthma.

    Staab, Elizabeth B; Sanderson, Sam D; Wells, Sandra M; Poole, Jill A

    2014-08-01

    Allergic asthma is a chronic inflammatory airway disease arising from an aberrant immune response following exposure to environmental stimuli in genetically susceptible persons. The complement component 5 (C5)/C5a Receptor (C5aR/CD88) signaling pathway has been implicated in both experimental allergic asthma and human asthmatic disease. Targeting the C5a/C5aR signaling pathway in rodent models has been shown to either enhance or reduce allergic asthma consequences. Treatment with a recombinant humanized monoclonal antibody directed against C5 has shown unclear results in patients with asthma. The objective of this proof-of-concept animal study was to determine whether the low molecular weight C5aR peptidomimetic antagonist, PMX205, would reduce experimental allergic asthma consequences in mice. PMX205 or vehicle control was administered subcutaneously to BALB/c mice prior to and during standard ovalbumin (OVA) allergen sensitization and aerosolized challenge phases. PMX205 substantially reduced OVA-induced total cell (60%), neutrophil (66%) and eosinophil (65%) influxes in lavage fluid sampling. There were also significant reductions in OVA-induced lavage fluid IL-13 protein and lung Th2 cytokine gene expression with PMX205 administration. PMX205 treatment also diminished OVA-induced lung parenchyma cellular infiltration. PMX205 administration did not reduce OVA-induced serum IgE levels or epithelial mucous/goblet cell generation. There was no evidence of toxicity observed with PMX205 treatment in saline or OVA-challenged animals. These data provide evidence that pharmacologic blockade of C5aR by a low molecular weight antagonist (PMX205) reduces airway inflammatory cell and cytokine responses in experimental allergic asthma, and suggests that PMX205 might represent a novel therapeutic agent for reducing asthmatic outcomes. PMID:24859057

  18. Grid adaptation using chimera composite overlapping meshes

    Kao, Kai-Hsiung; Liou, Meng-Sing; Chow, Chuen-Yen

    1994-01-01

    The objective of this paper is to perform grid adaptation using composite overlapping meshes in regions of large gradient to accurately capture the salient features during computation. The chimera grid scheme, a multiple overset mesh technique, is used in combination with a Navier-Stokes solver. The numerical solution is first converged to a steady state based on an initial coarse mesh. Solution-adaptive enhancement is then performed by using a secondary fine grid system which oversets on top of the base grid in the high-gradient region, but without requiring the mesh boundaries to join in any special way. Communications through boundary interfaces between those separated grids are carried out using trilinear interpolation. Application to the Euler equations for shock reflections and to shock wave/boundary layer interaction problem are tested. With the present method, the salient features are well-resolved.

  19. Grid adaption using Chimera composite overlapping meshes

    Kao, Kai-Hsiung; Liou, Meng-Sing; Chow, Chuen-Yen

    1993-01-01

    The objective of this paper is to perform grid adaptation using composite over-lapping meshes in regions of large gradient to capture the salient features accurately during computation. The Chimera grid scheme, a multiple overset mesh technique, is used in combination with a Navier-Stokes solver. The numerical solution is first converged to a steady state based on an initial coarse mesh. Solution-adaptive enhancement is then performed by using a secondary fine grid system which oversets on top of the base grid in the high-gradient region, but without requiring the mesh boundaries to join in any special way. Communications through boundary interfaces between those separated grids are carried out using tri-linear interpolation. Applications to the Euler equations for shock reflections and to a shock wave/boundary layer interaction problem are tested. With the present method, the salient features are well resolved.

  20. Controlling chimera states: The influence of excitable units

    Isele, Thomas; Hizanidis, Johanne; Provata, Astero; Hövel, Philipp

    2016-02-01

    We explore the influence of a block of excitable units on the existence and behavior of chimera states in a nonlocally coupled ring-network of FitzHugh-Nagumo elements. The FitzHugh-Nagumo system, a paradigmatic model in many fields from neuroscience to chemical pattern formation and nonlinear electronics, exhibits oscillatory or excitable behavior depending on the values of its parameters. Until now, chimera states have been studied in networks of coupled oscillatory FitzHugh-Nagumo elements. In the present work, we find that introducing a block of excitable units into the network may lead to several interesting effects. It allows for controlling the position of a chimera state as well as for generating a chimera state directly from the synchronous state.

  1. Fast clique minor generation in Chimera qubit connectivity graphs

    Boothby, Tomas; King, Andrew D.; Roy, Aidan

    2016-01-01

    The current generation of D-Wave quantum annealing processor is designed to minimize the energy of an Ising spin configuration whose pairwise interactions lie on the edges of a Chimera graph C_{M,N,L}. In order to solve an Ising spin problem with arbitrary pairwise interaction structure, the corresponding graph must be minor-embedded into a Chimera graph. We define a combinatorial class of native clique minors in Chimera graphs with vertex images of uniform, near minimal size and provide a polynomial-time algorithm that finds a maximum native clique minor in a given induced subgraph of a Chimera graph. These minors allow improvement over recent work and have immediate practical applications in the field of quantum annealing.

  2. Chimera states and excitation waves in networks with complex topologies

    Schöll, Eckehard

    2016-06-01

    Chimera patterns, which consist of coexisting spatial domains of coherent (synchronized) and incoherent (desyn- chronized) dynamics are studied in networks of FitzHugh-Nagumo systems with complex topologies. To test the robustness of chimera patterns with respect to changes in the structure of the network, we study the following network topologies: Regular ring topology with R nearest neigbors coupled to each side, small-world topology with additional long-range random links, and a hierarchical geometry in the connectivity matrix. We find that chimera states are generally robust with respect to these perturbations, but qualitative changes of the chimera patterns in form of nested coherent and incoherent regions can be induced by a hierarchical topology. The suppression of propagating excitation waves by a small-world topology is also reviewed.

  3. Nonlinearity of local dynamics promotes multi-chimeras

    Omelchenko, Iryna; Zakharova, Anna; Hoevel, Philipp; Siebert, Julien; Schoell, Eckehard

    2015-01-01

    Chimera states are complex spatio-temporal patterns in which domains of synchronous and asynchronous dynamics coexist in coupled systems of oscillators. We examine how the character of the individual elements influences chimera states by studying networks of nonlocally coupled Van der Pol oscillators. Varying the bifurcation parameter of the Van der Pol system, we can interpolate between regular sinusoidal and strongly nonlinear relaxation oscillations, and demonstrate that more pronounced no...

  4. Clustered chimera states in delay coupled oscillator systems

    Sethia, Gautam C.; Sen, Abhijit; Atay, Fatihcan M

    2008-01-01

    We investigate "chimera" states in a ring of identical phase oscillators coupled in a time-delayed and spatially non-local fashion. We find novel "clustered chimera" states that have spatially distributed phase coherence separated by incoherence with adjacent coherent regions in anti-phase. The existence of such time-delay induced phase clustering is further supported through solutions of a generalized functional self-consistency equation of the mean field. Our results highlight an additional...

  5. Chimera patterns in the Kuramoto-Battogtokh model

    Smirnov, L.A.; Osipov, G. V.; Pikovsky, A.

    2016-01-01

    Kuramoto and Battogtokh [Nonlinear Phenom. Complex Syst. 5, 380 (2002)] discovered chimera states represented by stable coexisting synchrony and asynchrony domains in a lattice of coupled oscillators. After reformulation in terms of local order parameter, the problem can be reduced to partial differential equations. We find uniformly rotating periodic in space chimera patterns as solutions of a reversible ordinary differential equation, and demonstrate a plethora of such states. In the limit ...

  6. Robustness of chimera states in complex dynamical systems

    Nan Yao; Zi-Gang Huang; Ying-Cheng Lai; Zhi-Gang Zheng

    2013-01-01

    The remarkable phenomenon of chimera state in systems of non-locally coupled, identical oscillators has attracted a great deal of recent theoretical and experimental interests. In such a state, different groups of oscillators can exhibit characteristically distinct types of dynamical behaviors, in spite of identity of the oscillators. But how robust are chimera states against random perturbations to the structure of the underlying network? We address this fundamental issue by studying the eff...

  7. Controlling Chimera States - The influence of excitable units

    Isele, Thomas; Hizanidis, Johanne; Provata, Astero; Hövel, Philipp

    2015-01-01

    We explore the influence of a block of excitable units on the existence and behavior of chimera states in a nonlocally coupled ring-network of FitzHugh-Nagumo elements. The FitzHugh-Nagumo system, a paradigmatic model in many fields from neuroscience to chemical pattern formation and nonlinear electronics, exhibits oscillatory or excitable behavior depending on the values of its parameters. Until now, chimera states have been studied in networks of coupled oscillatory FitzHugh-Nagumo elements...

  8. Self-organized alternating chimera states in oscillatory media

    Haugland, Sindre W.; Schmidt, Lennart; Krischer, Katharina

    2014-01-01

    Oscillatory media can exhibit the coexistence of synchronized and desynchronized regions, so-called chimera states, for uniform parameters and symmetrical coupling. In a phase-balanced chimera state, where the totals of synchronized and desynchronized regions, respectively, are of the same size, the symmetry of the system predicts that interchanging both phases still gives a solution to the underlying equations. We observe this kind of interchange as a self-emerging phenomenon in an oscillato...

  9. Chimera death induced by the mean-field diffusive coupling

    Banerjee, Tanmoy

    2014-01-01

    Recently a novel dynamical state, called the {\\it chimera death}, is discovered in a network of non locally coupled identical oscillators [A. Zakharova, M. Kapeller, and E. Sch\\"oll, Phy.Rev.Lett. 112, 154101 (2014)], which is defined as the coexistence of spatially coherent and incoherent oscillation death state. This state arises due to the interplay of non locality and symmetry breaking and thus bridges the gap between two important dynamical states, namely the chimera and oscillation deat...

  10. Phase-flip chimera induced by environmental nonlocal coupling

    Chandrasekar, V. K.; Gopal, R.; Senthilkumar, D. V.; Lakshmanan, M.

    2016-07-01

    We report the emergence of a collective dynamical state, namely, the phase-flip chimera, from an ensemble of identical nonlinear oscillators that are coupled indirectly via the dynamical variables from a common environment, which in turn are nonlocally coupled. The phase-flip chimera is characterized by the coexistence of two adjacent out-of-phase synchronized coherent domains interspersed by an incoherent domain, in which the nearby oscillators are in out-of-phase synchronized states. Attractors of the coherent domains are either from the same or from different basins of attractions, depending on whether they are periodic or chaotic. The conventional chimera precedes the phase-flip chimera in general. Further, the phase-flip chimera emerges after the completely synchronized evolution of the ensemble, in contrast to conventional chimeras, which emerge as an intermediate state between completely incoherent and coherent states. We have also characterized the observed dynamical transitions using the strength of incoherence, probability distribution of the correlation coefficient, and framework of the master stability function.

  11. The costs and benefits of being a chimera.

    Foster, Kevin R; Fortunato, Angelo; Strassmann, Joan E; Queller, David C

    2002-11-22

    Most multicellular organisms are uniclonal. This is hypothesized to be because uniclonal organisms function better than chimeras (non-clonal organisms), owing to reduced levels of internal genetic conflict. We tested this idea using the social amoeba or slime mold Dictyostelium discoideum. When starving, the normally solitary amoebae aggregate to form a differentiated multicellular slug that migrates towards light and forms a fruiting body, facilitating the dispersal of spores. We added 10(7) amoebae to Petri plates containing 1, 2, 5 or 10 clones mixed together. We found an intrinsic cost to chimerism: chimeric slugs moved significantly less far than uniclonal slugs of the same size. However, in nature, joining with other clones to form a chimera should increase slug size, and larger slugs travel further. We incorporated this size effect into a second experiment by giving chimeras more cells than single clones (single clones had 10(6) cells, two-clone chimeras had 2 x 10(6) cells and so on). The uniclonal treatments then simulated a clone in a mixture that refuses to form chimeras. In this experiment, chimeras moved significantly further than the uniclonal slugs, in spite of the intrinsic cost. Thus, chimerism is costly, which may be why it evolves so seldom, but in D. discoideum the benefits of large size appear to compensate. PMID:12495504

  12. Characteristics of macrophages in irradiation chimeras in mice reconstituted with allogeneic bone marrow cells

    Biological and immunological characteristics of the reticuloendothelial system of irradiation bone marrow chimeric mice and macrophages collected from various tissue sources of the mice were studied. The chimeras showed comparable activities in carbon clearance to those of normal donor or recipient mice. The macrophages from spleen, lymph node, bone marrow, peripheral blood, liver, peritoneal cavity, and lung were demonstrated to be of donor marrow origin. They showed almost the same enzyme activities and phagocytic capability of sheep erythrocytes (SRBC, E), SRBC sensitized with anti-SRBC IgG (EA), and SRBC sensitized with anti-SRBC IgM and coated with complement (EAC) as those of normal mice. Proportions of Fc receptor and complement receptor-positive cells are also in normal range. In addition, the antigen-presenting capability of the chimeric macrophages for in vitro primary antibody response to SRBC was intact. These observations suggest that the reticuloendothelial system and macrophages of allogeneic bone marrow chimeras where donor and recipient differ at the major histocompatibility complex have no defect so far as could be ascertained by the present study

  13. Epitope Mapping of Neutralizing Monoclonal Antibodies to Human Interferon-γ Using Human-Bovine Interferon-γ Chimeras

    Zuber, Bartek; Rudström, Karin; Ehrnfelt, Cecilia

    2016-01-01

    Our aim was to identify conformational epitopes, recognized by monoclonal antibodies (mAbs) made against human (h) interferon (IFN)-γ. Based on the mAbs' (n = 12) ability to simultaneously bind hIFN-γ in ELISA, 2 epitope clusters with 5 mAbs in each were defined; 2 mAbs recognized unique epitopes. Utilizing the mAbs' lack of reactivity with bovine (b) IFN-γ, epitopes were identified using 7 h/bIFN-γ chimeras where the helical regions (A-F) or the C terminus were substituted with bIFN-γ residues. Chimeras had a N-terminal peptide tag enabling the analysis of mAb recognition of chimeras in ELISA. The 2 mAb clusters mapped to region A and E, respectively; the epitopes of several mAbs also involved additional regions. MAbs in cluster A neutralized, to various degrees, IFN-γ-mediated activation of human cells, in line with the involvement of region A in the IFN-γ receptor interaction. MAbs mapping to region E displayed a stronger neutralizing capacity although this region has not been directly implicated in the receptor interaction. The results corroborate earlier studies and provide a detailed picture of the link between the epitope specificity and neutralizing capacity of mAbs. They further demonstrate the general use of peptide-tagged chimeric proteins as a powerful and straightforward method for efficient mapping of conformational epitopes. PMID:27336613

  14. Epitope Mapping of Neutralizing Monoclonal Antibodies to Human Interferon-γ Using Human-Bovine Interferon-γ Chimeras.

    Zuber, Bartek; Rudström, Karin; Ehrnfelt, Cecilia; Ahlborg, Niklas

    2016-09-01

    Our aim was to identify conformational epitopes, recognized by monoclonal antibodies (mAbs) made against human (h) interferon (IFN)-γ. Based on the mAbs' (n = 12) ability to simultaneously bind hIFN-γ in ELISA, 2 epitope clusters with 5 mAbs in each were defined; 2 mAbs recognized unique epitopes. Utilizing the mAbs' lack of reactivity with bovine (b) IFN-γ, epitopes were identified using 7 h/bIFN-γ chimeras where the helical regions (A-F) or the C terminus were substituted with bIFN-γ residues. Chimeras had a N-terminal peptide tag enabling the analysis of mAb recognition of chimeras in ELISA. The 2 mAb clusters mapped to region A and E, respectively; the epitopes of several mAbs also involved additional regions. MAbs in cluster A neutralized, to various degrees, IFN-γ-mediated activation of human cells, in line with the involvement of region A in the IFN-γ receptor interaction. MAbs mapping to region E displayed a stronger neutralizing capacity although this region has not been directly implicated in the receptor interaction. The results corroborate earlier studies and provide a detailed picture of the link between the epitope specificity and neutralizing capacity of mAbs. They further demonstrate the general use of peptide-tagged chimeric proteins as a powerful and straightforward method for efficient mapping of conformational epitopes. PMID:27336613

  15. Development of surface-based assays for transmembrane proteins: selective immobilization of functional CCR5, a G protein-coupled receptor.

    Silin, Vitalii I; Karlik, Evan A; Ridge, Kevin D; Vanderah, David J

    2006-02-15

    A general method to develop surface-based assays for transmembrane (TM) receptor function(s) without the need to isolate, purify, and reconstitute the proteins is presented. Based on the formation of an active surface that selectively immobilizes membrane vesicles, the method is illustrated using the chemokine receptor CCR5, a member of the largest family of cell surface eukaryotic TM proteins, the G protein-coupled receptors (GPCRs). The method begins with a protein-resistant surface containing a low percentage (1-5%) of surface-bound biotin on gold as the initial template. Surface plasmon resonance (SPR) data show specific immobilization of functional CCR5 after the initial template is activated by immobilization of rho 1D4 antibody, an anti-rhodopsin monoclonal antibody specific for the carboxyl terminal nine amino acids on bovine rhodopsin that had been engineered into the carboxyl terminus of CCR5, and exposure to vesicles obtained from mammalian cells transfected with a synthetic human CCR5 gene. Activation of the initial template is effected by sequential immobilization of avidin, which binds to the biotin in the initial template, a biotinylated goat anti-mouse immunoglobulin G (Bt-IgG), which binds to the avidin binding sites distal to the surface and the F(c) portion of the rho 1D4 antibody through its F(ab) region(s) and finally rho 1D4. This approach establishes a broad outline for the development and application of various assays for CCR5 functions. SPR data also showed that vesicle immobilization could be achieved through an integrin-integrin antibody interaction after activation of the initial template with a goat anti-human integrin beta1 antibody. These results suggest that the generic nature of the initial platform and flexibility of the subsequent surface activation for specific immobilization of membrane vesicles can be applied to the development of assays for other GPCRs or TM receptors for which antibodies are available or can be engineered to

  16. Epitopes associated with the MHC restriction site of T cells. II. Somatic generation of Iat epitopes on T cells in radiation bone marrow chimeras

    Asano, Y.; Tada, T.

    1987-01-01

    We described in this paper systematic alterations in the expression of unique I region controlled epitopes on helper T cells (Th) in chimeras according to the changes in their H-2 restriction specificity. Taking advantage of the reactivity of monoclonal antibodies (anti-Iat) putatively specific for the epitopes indirectly controlled by I region and expressed in association with the Iak restriction site of Th, we examined the alterations of these epitopes on Th cells from various bone marrow chimeras. Iatk epitopes were physiologically expressed on Iak-restricted but not on Iab-restricted Th cells in (H-2k X H-2b)F1 mice. In the chimeric condition, the H-2k-restricted Th of B6----F1 chimera acquired the expression of Iatk even though B6 Th is unable to express Iatk when developed under the physiologic condition. Iatk are also found on Th of fully allogeneic chimera of B6----C3H, whereas Th cells of C3H----B6 completely lost the Iatk expression. These results indicate that Iat epitopes originally defined as unique I region-controlled determinants selectively expressed on T cells are not encoded by the I region genes but are associated with the T cell receptor that sees the self Ia. The epitopes undergo the adaptive alterations according to the acquisition of a new MHC restriction. This is the first example to demonstrate the epitope associated with T cell receptor which undergo the systematic adaptive differentiation.

  17. Epitopes associated with the MHC restriction site of T cells. II. Somatic generation of Iat epitopes on T cells in radiation bone marrow chimeras

    We described in this paper systematic alterations in the expression of unique I region controlled epitopes on helper T cells (Th) in chimeras according to the changes in their H-2 restriction specificity. Taking advantage of the reactivity of monoclonal antibodies (anti-Iat) putatively specific for the epitopes indirectly controlled by I region and expressed in association with the Iak restriction site of Th, we examined the alterations of these epitopes on Th cells from various bone marrow chimeras. Iatk epitopes were physiologically expressed on Iak-restricted but not on Iab-restricted Th cells in (H-2k X H-2b)F1 mice. In the chimeric condition, the H-2k-restricted Th of B6----F1 chimera acquired the expression of Iatk even though B6 Th is unable to express Iatk when developed under the physiologic condition. Iatk are also found on Th of fully allogeneic chimera of B6----C3H, whereas Th cells of C3H----B6 completely lost the Iatk expression. These results indicate that Iat epitopes originally defined as unique I region-controlled determinants selectively expressed on T cells are not encoded by the I region genes but are associated with the T cell receptor that sees the self Ia. The epitopes undergo the adaptive alterations according to the acquisition of a new MHC restriction. This is the first example to demonstrate the epitope associated with T cell receptor which undergo the systematic adaptive differentiation

  18. Tools for integrated sequence-structure analysis with UCSF Chimera

    Huang Conrad C

    2006-07-01

    Full Text Available Abstract Background Comparing related structures and viewing the structures in the context of sequence alignments are important tasks in protein structure-function research. While many programs exist for individual aspects of such work, there is a need for interactive visualization tools that: (a provide a deep integration of sequence and structure, far beyond mapping where a sequence region falls in the structure and vice versa; (b facilitate changing data of one type based on the other (for example, using only sequence-conserved residues to match structures, or adjusting a sequence alignment based on spatial fit; (c can be used with a researcher's own data, including arbitrary sequence alignments and annotations, closely or distantly related sets of proteins, etc.; and (d interoperate with each other and with a full complement of molecular graphics features. We describe enhancements to UCSF Chimera to achieve these goals. Results The molecular graphics program UCSF Chimera includes a suite of tools for interactive analyses of sequences and structures. Structures automatically associate with sequences in imported alignments, allowing many kinds of crosstalk. A novel method is provided to superimpose structures in the absence of a pre-existing sequence alignment. The method uses both sequence and secondary structure, and can match even structures with very low sequence identity. Another tool constructs structure-based sequence alignments from superpositions of two or more proteins. Chimera is designed to be extensible, and mechanisms for incorporating user-specific data without Chimera code development are also provided. Conclusion The tools described here apply to many problems involving comparison and analysis of protein structures and their sequences. Chimera includes complete documentation and is intended for use by a wide range of scientists, not just those in the computational disciplines. UCSF Chimera is free for non-commercial use and is

  19. Light inactivation of water transport and protein–protein interactions of aquaporin–Killer Red chimeras

    Baumgart, Florian; Rossi, Andrea

    2012-01-01

    Aquaporins (AQPs) have a broad range of cellular and organ functions; however, nontoxic inhibitors of AQP water transport are not available. Here, we applied chromophore-assisted light inactivation (CALI) to inhibit the water permeability of AQP1, and of two AQP4 isoforms (M1 and M23), one of which (M23) forms aggregates at the cell plasma membrane. Chimeras containing Killer Red (KR) and AQPs were generated with linkers of different lengths. Osmotic water permeability of cells expressing KR/AQP chimeras was measured from osmotic swelling–induced dilution of cytoplasmic chloride, which was detected using a genetically encoded chloride-sensing fluorescent protein. KR-AQP1 red fluorescence was bleached rapidly (∼10% per second) by wide-field epifluorescence microscopy. After KR bleaching, KR-AQP1 water permeability was reduced by up to 80% for the chimera with the shortest linker. Remarkably, CALI-induced reduction in AQP4-KR water permeability was approximately twice as efficient for the aggregate-forming M23 isoform; this suggests intermolecular CALI, which was confirmed by native gel electrophoresis on cells coexpressing M23-AQP4-KR and myc-tagged M23-AQP4. CALI also disrupted the interaction of AQP4 with a neuromyelitis optica autoantibody directed against an extracellular epitope on AQP4. CALI thus permits rapid, spatially targeted and irreversible reduction in AQP water permeability and interactions in live cells. Our data also support the utility of CALI to study protein–protein interactions as well as other membrane transporters and receptors. PMID:22200949

  20. Modeling Quark Gluon Plasma Using CHIMERA

    Abelev, Betty B I

    2011-01-01

    We attempt to model Quark Gluon Plasma (QGP) evolution from the initial Heavy Ion collision to the final hadronic gas state by combining the Glauber model initial state conditions with eccentricity fluctuations, pre-equilibrium flow, UVH2+1 viscous hydrodynamics with lattice QCD Equation of State (EoS), a modified Cooper-Frye freeze-out and the UrQMD hadronic cascade. We then evaluate the model parameters using a comprehensive analytical framework which together with the described model we call CHIMERA. Within our framework, the initial state parameters, such as the initial temperature (T$_{\\mathrm{init}}$), presence or absence of initial flow, viscosity over entropy density ($\\eta$/s) and different Equations of State (EoS), are varied and then compared simultaneously to several experimental data observables: HBT radii, particle spectra and particle flow. $\\chi^2$/nds values from comparison to the experimental data for each set of initial parameters will then used to find the optimal description of the QGP wi...

  1. Model bridging chimera state and explosive synchronization

    Zhang, Xiyun; Bi, Hongjie; Guan, Shuguang; Liu, Jinming; Liu, Zonghua

    2016-07-01

    Global synchronization and partial synchronization are the two distinctive forms of synchronization in coupled oscillators and have been well studied in recent decades. Recent attention on synchronization is focused on the chimera state (CS) and explosive synchronization (ES), but little attention has been paid to their relationship. Here we study this topic by presenting a model to bridge these two phenomena, which consists of two groups of coupled oscillators, and its coupling strength is adaptively controlled by a local order parameter. We find that this model displays either CS or ES in two limits. In between the two limits, this model exhibits both CS and ES, where CS can be observed for a fixed coupling strength and ES appears when the coupling is increased adiabatically. Moreover, we show both theoretically and numerically that there are a variety of CS basin patterns for the case of identical oscillators, depending on the distributions of both the initial order parameters and the initial average phases. This model suggests a way to easily observe CS, in contrast to other models having some (weak or strong) dependence on initial conditions.

  2. Allogeneic radiation chimeras: long-term studies

    Lethally irradiated mice protected with allogeneic fetal liver cells or with syngeneic or allogeneic marrow and spleen cells treated with antisera to mouse immunoglobulins or to the T cell-associated 0 antigen and their controls were observed for up to 750 days. The best survival rates were found in the large groups given syngeneic marrow and spleen or allogeneic fetal liver cells (70-85 percent 700-day survival); in contrast, 43 percent of the group injected with allogeneic cells treated with anti-0 serum and 19 percent of those given antimmunoglobulin-treated cells were alive 700 days postradiation. Pulmonary infection was the most frequent cause of death of long-term survivors in all groups. Tumor incidence was increased in recipients of allogeneic cells (13 percent versus 4 percent among syngeneic chimeras), but the renal pathology seen in these groups was no greater than that noted in the syngeneic controls. Beginning 600 days after irradiation, mice from experimental and control groups were killed and their spleens were cultured with thymus-dependent antigens and the mitogens concanavalin Λ and lipopolysaccharide, Escherichia coli. The most frequent finding in all groups was mild to moderate impairment of T cell-dependent responses. (U.S.)

  3. Chimera states in coupled Kuramoto oscillators with inertia

    Olmi, Simona

    2015-12-01

    The dynamics of two symmetrically coupled populations of rotators is studied for different values of the inertia. The system is characterized by different types of solutions, which all coexist with the fully synchronized state. At small inertia, the system is no more chaotic and one observes mainly quasi-periodic chimeras, while the usual (stationary) chimera state is not anymore observable. At large inertia, one observes two different kind of chaotic solutions with broken symmetry: the intermittent chaotic chimera, characterized by a synchronized population and a population displaying a turbulent behaviour, and a second state where the two populations are both chaotic but whose dynamics adhere to two different macroscopic attractors. The intermittent chaotic chimeras are characterized by a finite life-time, whose duration increases as a power-law with the system size and the inertia value. Moreover, the chaotic population exhibits clear intermittent behavior, displaying a laminar phase where the two populations tend to synchronize, and a turbulent phase where the macroscopic motion of one population is definitely erratic. In the thermodynamic limit, these states survive for infinite time and the laminar regimes tends to disappear, thus giving rise to stationary chaotic solutions with broken symmetry contrary to what observed for chaotic chimeras on a ring geometry.

  4. Chimera states in coupled Kuramoto oscillators with inertia

    The dynamics of two symmetrically coupled populations of rotators is studied for different values of the inertia. The system is characterized by different types of solutions, which all coexist with the fully synchronized state. At small inertia, the system is no more chaotic and one observes mainly quasi-periodic chimeras, while the usual (stationary) chimera state is not anymore observable. At large inertia, one observes two different kind of chaotic solutions with broken symmetry: the intermittent chaotic chimera, characterized by a synchronized population and a population displaying a turbulent behaviour, and a second state where the two populations are both chaotic but whose dynamics adhere to two different macroscopic attractors. The intermittent chaotic chimeras are characterized by a finite life-time, whose duration increases as a power-law with the system size and the inertia value. Moreover, the chaotic population exhibits clear intermittent behavior, displaying a laminar phase where the two populations tend to synchronize, and a turbulent phase where the macroscopic motion of one population is definitely erratic. In the thermodynamic limit, these states survive for infinite time and the laminar regimes tends to disappear, thus giving rise to stationary chaotic solutions with broken symmetry contrary to what observed for chaotic chimeras on a ring geometry

  5. Chimera states in coupled Kuramoto oscillators with inertia

    Olmi, Simona, E-mail: simona.olmi@fi.isc.cnr.it [CNR - Consiglio Nazionale delle Ricerche - Istituto dei Sistemi Complessi, via Madonna del Piano 10, I-50019 Sesto Fiorentino (Italy); INFN Sez. Firenze, via Sansone, 1 - I-50019 Sesto Fiorentino (Italy)

    2015-12-15

    The dynamics of two symmetrically coupled populations of rotators is studied for different values of the inertia. The system is characterized by different types of solutions, which all coexist with the fully synchronized state. At small inertia, the system is no more chaotic and one observes mainly quasi-periodic chimeras, while the usual (stationary) chimera state is not anymore observable. At large inertia, one observes two different kind of chaotic solutions with broken symmetry: the intermittent chaotic chimera, characterized by a synchronized population and a population displaying a turbulent behaviour, and a second state where the two populations are both chaotic but whose dynamics adhere to two different macroscopic attractors. The intermittent chaotic chimeras are characterized by a finite life-time, whose duration increases as a power-law with the system size and the inertia value. Moreover, the chaotic population exhibits clear intermittent behavior, displaying a laminar phase where the two populations tend to synchronize, and a turbulent phase where the macroscopic motion of one population is definitely erratic. In the thermodynamic limit, these states survive for infinite time and the laminar regimes tends to disappear, thus giving rise to stationary chaotic solutions with broken symmetry contrary to what observed for chaotic chimeras on a ring geometry.

  6. Amplitude-phase coupling drives chimera states in globally coupled laser networks

    Böhm, Fabian; Zakharova, Anna; Schöll, Eckehard; Lüdge, Kathy

    2014-01-01

    For a globally coupled network of semiconductor lasers with delayed optical feedback, we demonstrate the existence of chimera states. The domains of coherence and incoherence that are typical for chimera states are found to exist for the amplitude, phase, and inversion of the coupled lasers. These chimera states defy several of the previously established existence criteria. While chimera states in phase oscillators generally demand nonlocal coupling, large system sizes, and specially prepared...

  7. Deterministic and stochastic control of chimera states in delayed feedback oscillator

    Semenov, V.; Zakharova, A.; Maistrenko, Y.; Schöll, E.

    2016-06-01

    Chimera states, characterized by the coexistence of regular and chaotic dynamics, are found in a nonlinear oscillator model with negative time-delayed feedback. The control of these chimera states by external periodic forcing is demonstrated by numerical simulations. Both deterministic and stochastic external periodic forcing are considered. It is shown that multi-cluster chimeras can be achieved by adjusting the external forcing frequency to appropriate resonance conditions. The constructive role of noise in the formation of a chimera states is shown.

  8. Experimental study of jittering chimeras in a ring of excitable units

    Klinshov, Vladimir; Shchapin, Dmitry; Lücken, Leonhard; Yanchuk, Serhiy; Nekorkin, Vladimir

    2016-06-01

    A new type of chimera-like regime is reported that we call "jittering chimera". The regime is observed in a ring of excitable units in which the excitation is invoked by an oscillator included into the ring. The jittering chimera is characterized by the presence of two domains, one with regular spiking and the other with irregular. A method to set and control desired chimera states in a physically implemented electronic circuit is developed.

  9. Multi-chimera states in the Leaky Integrate-and-Fire model

    Tsigkri-DeSmedt, N. D.; Hizanidis, J.; Hoevel, P.; A. Provata

    2015-01-01

    We study the dynamics of identical leaky integrate-and-fire neurons with symmetric non-local coupling. Upon varying control parameters (coupling strength, coupling range, refractory period) we investigate the system's behaviour and highlight the formation of chimera states. We show that the introduction of a refractory period enlarges the parameter region where chimera states appear and affects the chimera multiplicity.

  10. Chimera-like states in modular neural networks

    Hizanidis, Johanne; Zamora-López, Gorka; Díaz-Guilera, Albert; Antonopoulos, Chris G

    2016-01-01

    Chimera states, namely the coexistence of coherent and incoherent behavior, were previously analyzed in complex networks. However, they have not been extensively studied in modular networks. Here, we consider the neural network of the \\textit{C.elegans} soil worm, organized into six interconnected communities, where neurons obey chaotic bursting dynamics. Neurons are assumed to be connected with electrical synapses within their communities and with chemical synapses across them. As our numerical simulations reveal, the coaction of these two types of coupling can shape the dynamics in such a way that chimera-like states can happen. They consist of a fraction of synchronized neurons which belong to the larger communities, and a fraction of desynchronized neurons which are part of smaller communities. In addition to the Kuramoto order parameter $\\rho$, we also employ other measures of coherence, such as the chimera-like $\\chi$ and metastability $\\lambda$ indices, which quantify the degree of synchronization amon...

  11. Chimera-type states induced by local coupling

    Clerc, M. G.; Coulibaly, S.; Ferré, M. A.; García-Ñustes, M. A.; Rojas, R. G.

    2016-05-01

    Coupled oscillators can exhibit complex self-organization behavior such as phase turbulence, spatiotemporal intermittency, and chimera states. The latter corresponds to a coexistence of coherent and incoherent states apparently promoted by nonlocal or global coupling. Here we investigate the existence, stability properties, and bifurcation diagram of chimera-type states in a system with local coupling without different time scales. Based on a model of a chain of nonlinear oscillators coupled to adjacent neighbors, we identify the required attributes to observe these states: local coupling and bistability between a stationary and an oscillatory state close to a homoclinic bifurcation. The local coupling prevents the incoherent state from invading the coherent one, allowing concurrently the existence of a family of chimera states, which are organized by a homoclinic snaking bifurcation diagram.

  12. Chimeras in locally coupled SQUIDs: Lions, goats and snakes

    Hizanidis, J; Tsironis, G P

    2016-01-01

    We report on the emergence of robust multi-clustered chimera states in a dissipative-driven system of symmetrically and locally coupled identical SQUID oscillators. The "snake-like" resonance curve of the single SQUID (Superconducting QUantum Interference Device) is the key to the formation of the chimera states and is responsible for the extreme multistability exhibited by the coupled system that leads to attractor crowding at the geometrical resonance frequency. Until now, chimera states were mostly believed to exist for nonlocal coupling. Our findings provide theoretical evidence that nearest neighbor interactions is indeed capable of supporting such states in a wide parameter range. SQUID metamaterials are the subject of intense experimental investigations and we are highly confident that the complex dynamics demonstrated in this manuscript can be confirmed in the laboratory.

  13. Progress in Grid Generation: From Chimera to DRAGON Grids

    Liou, Meng-Sing; Kao, Kai-Hsiung

    1994-01-01

    Hybrid grids, composed of structured and unstructured grids, combines the best features of both. The chimera method is a major stepstone toward a hybrid grid from which the present approach is evolved. The chimera grid composes a set of overlapped structured grids which are independently generated and body-fitted, yielding a high quality grid readily accessible for efficient solution schemes. The chimera method has been shown to be efficient to generate a grid about complex geometries and has been demonstrated to deliver accurate aerodynamic prediction of complex flows. While its geometrical flexibility is attractive, interpolation of data in the overlapped regions - which in today's practice in 3D is done in a nonconservative fashion, is not. In the present paper we propose a hybrid grid scheme that maximizes the advantages of the chimera scheme and adapts the strengths of the unstructured grid while at the same time keeps its weaknesses minimal. Like the chimera method, we first divide up the physical domain by a set of structured body-fitted grids which are separately generated and overlaid throughout a complex configuration. To eliminate any pure data manipulation which does not necessarily follow governing equations, we use non-structured grids only to directly replace the region of the arbitrarily overlapped grids. This new adaptation to the chimera thinking is coined the DRAGON grid. The nonstructured grid region sandwiched between the structured grids is limited in size, resulting in only a small increase in memory and computational effort. The DRAGON method has three important advantages: (1) preserving strengths of the chimera grid; (2) eliminating difficulties sometimes encountered in the chimera scheme, such as the orphan points and bad quality of interpolation stencils; and (3) making grid communication in a fully conservative and consistent manner insofar as the governing equations are concerned. To demonstrate its use, the governing equations are

  14. Existence of Chimera State on Two Parallel Circles

    Lin, Larry; Yang, Pei-Kun

    2016-06-01

    A nonlocal coupling system with oscillators on two parallel circles can evolve into a chimera state for suitable values of the parameters α and β. The parameter β is the distance between the circles and affects the phase-locked areas of the chimera state. The Kuramoto theory successfully describes whether and where the oscillators are phase-locked or drifting. The position difference ΔX describes the displacement of phase-locked areas between the circles. The dynamics of the model with four oscillators also show similar phenomena. The position difference ΔX results from the arrangement of oscillators on the two parallel circles.

  15. Mechanisms of tolerance in murine radiation bone marrow chimeras. II. Absence of nonspecific suppression in mature chimeras

    Spleen cells from a series of allogeneic bone marrow chimeras were sensitized in vitro with stimulator cells from major histocompatibility complex recombinant strains of mice. The combinations were chosen such that both tolerated (host or donor) and nontolerated (third-party) antigens were present on the same stimulator cells in order to determine whether the tolerated host antigens might elicit nonspecific suppressor mechanisms affecting the cell-mediated lympholysis (CML) response to the nontolerated antigens. No evidence for such nonspecific suppression was obtained in several types of assays. Therefore, if suppressor mechanisms exist that mediate such tolerance in mature allogeneic chimeras then these mechanisms must be highly antigen-specific

  16. Characterization of host lymphoid cells in antibody-facilitated bone marrow chimeras

    The authors have produced stable murine antibody-facilitated (AF) chimeras by the simultaneous injection of P1 bone marrow cells and anti-P2 monoclonal antibody into normal (unirradiated) adult (P1 X P2)F1 recipients. These AF chimeras are healthy, long-lived, and exhibit no overt signs of graft-versus-host disease. They are immunocompetent and tolerant of host, P2-encoded alloantigens. Donor cell engraftment and takeover, monitored by glucosephosphate isomerase isozyme patterns, is usually complete (greater than 95%) in the peripheral blood, bone marrow, and hemopoietic stem cell compartments of long-term (greater than 3 months posttransplantation) AF chimeras. The authors report here, however, that splenic, lymph node, and thymic leukocytes of AF chimeras represent donor/host chimeric populations. Spleen cell populations of AF chimeras exhibit substantial chimera-to-chimera variation in the preponderant residual host cell type(s) present. Interpretations of the implications of these findings are discussed

  17. CHIMERA CBRN protective suit. Advanced embodiment design. Final report

    Bogerd, C.P.; Smit, B. de; Olarte, C.; Kane, G.; Bie, M. de; Megen, X. van; Schenk, J.; Hooop, J. de

    2015-01-01

    The Chimera project started of with the following design challenge: Designing a switchable CBRN (chemical, biological, radiological, nuclear) protective suit for soldiers, one phase being a regular work state and the other phase being a protective state to enable the soldier to get away from the tox

  18. Radiobiological researches on Dianthus caryophyllus L. carnation chimeras

    This research thesis reports a radiobiological study of Dianthus periclinal chimeras performed by submitting plants and plant cuttings at different physiological stages to cobalt-60 gamma irradiation under different dose conditions and rates. The effects of these treatments are studied while growing the so-processed plants and by microscopic examination of sections of irradiated meristems

  19. Resistance to BN myelogenous leukemia in rat radiation chimeras

    Lewis → LBNFl rat radiation chimeras showed marked resistance to transplanted BN myelogenous leukemia when compared to naive LBNFl, LBNFl → LBNFl, or BN → LBNFl. This occurred in the absence of overt graft versus host disease or of anti-BN response in mixed lymphocyte culture. Bone marrow specific antigens may serve as the target of the resistance mechanism. (author)

  20. Use of fragmentation beams at LNS with CHIMERA detector

    Gianí R.; Francalanza L.; DeFilippo E.; Chatterjiee M.B.; Buscemi M.; Berceanu I.; Auditore L.; Anzalone A.; Amorini F.; Agodi C.; Acosta L.; Cardella G.; Grassi L.; La Guidara E.; Lanzalone G.

    2012-01-01

    The recent intensity upgrade of the LNS fragmentation beam is discussed. The available beams, the tagging procedures and details on the beam quality are reported. The experimental program started with the CHIMERA detector using such beams is also discussed with preliminary results and future perspectives.

  1. Use of fragmentation beams at LNS with CHIMERA detector

    Gianí R.

    2012-07-01

    Full Text Available The recent intensity upgrade of the LNS fragmentation beam is discussed. The available beams, the tagging procedures and details on the beam quality are reported. The experimental program started with the CHIMERA detector using such beams is also discussed with preliminary results and future perspectives.

  2. Radiochemical synthesis and biological evaluation of 3-[4-(4-[{sup 18}F]fluorobenzyl)piperazin-1-ylmethyl]pyrazolo[1,5-a]pyridine as dopamine D{sub 4} receptor radioligand

    Li, Gu-Cai; Zhang, Ru; Jiang, Kai-Jun; Chen, Bo [Hunan Institute of Engineering, Xiangtan (China). College of Chemistry and Chemical Engineering

    2014-09-01

    A potential dopamine D{sub 4} receptor radioligand, 3-[4-(4-[{sup 18}F]fluorobenzyl)piperazin-1-ylmethyl]pyrazolo[1,5-a]pyridine was synthesized through a one-pot two-step procedure with total yield 18.5% (decay corrected). The molar radioactivity was 115 GBq/μmol and the radiochemical purity was greater than 95.5%. Its affinity and selectivity for dopamine D{sub 2}-like receptors were measured through in vitro receptor binding experiments and the K{sub i} for D{sub 4} receptor was determined to be 17 ± 0.5 nM. The partition coefficient (Log P) of it was determined to be 2.80 ± 0.10 through octanol experiment. The in vivo biodistribution of it in rat brain exposed that the radioligand penetrates through blood-brain- barrier (BBB) and may specifically bind to dopamine D{sub 4} receptor. The results indicated that the radioligand shows promise for the in vivo study of dopamine D{sub 4} receptor. (orig.)

  3. Radiochemical synthesis and biological evaluation of 3-[4-(4-[18F]fluorobenzyl)piperazin-1-ylmethyl]pyrazolo[1,5-a]pyridine as dopamine D4 receptor radioligand

    A potential dopamine D4 receptor radioligand, 3-[4-(4-[18F]fluorobenzyl)piperazin-1-ylmethyl]pyrazolo[1,5-a]pyridine was synthesized through a one-pot two-step procedure with total yield 18.5% (decay corrected). The molar radioactivity was 115 GBq/μmol and the radiochemical purity was greater than 95.5%. Its affinity and selectivity for dopamine D2-like receptors were measured through in vitro receptor binding experiments and the Ki for D4 receptor was determined to be 17 ± 0.5 nM. The partition coefficient (Log P) of it was determined to be 2.80 ± 0.10 through octanol experiment. The in vivo biodistribution of it in rat brain exposed that the radioligand penetrates through blood-brain- barrier (BBB) and may specifically bind to dopamine D4 receptor. The results indicated that the radioligand shows promise for the in vivo study of dopamine D4 receptor. (orig.)

  4. Amplitude-phase coupling drives chimera states in globally coupled laser networks

    Böhm, Fabian; Zakharova, Anna; Schöll, Eckehard; Lüdge, Kathy

    2015-04-01

    For a globally coupled network of semiconductor lasers with delayed optical feedback, we demonstrate the existence of chimera states. The domains of coherence and incoherence that are typical for chimera states are found to exist for the amplitude, phase, and inversion of the coupled lasers. These chimera states defy several of the previously established existence criteria. While chimera states in phase oscillators generally demand nonlocal coupling, large system sizes, and specially prepared initial conditions, we find chimera states that are stable for global coupling in a network of only four coupled lasers for random initial conditions. The existence is linked to a regime of multistability between the synchronous steady state and asynchronous periodic solutions. We show that amplitude-phase coupling, a concept common in different fields, is necessary for the formation of the chimera states.

  5. Amplitude-phase coupling drives chimera states in globally coupled laser networks

    Böhm, Fabian; Schöll, Eckehard; Lüdge, Kathy

    2014-01-01

    For a globally coupled network of semiconductor lasers with delayed optical feedback, we demonstrate the existence of chimera states. The domains of coherence and incoherence that are typical for chimera states are found to exist for the amplitude, phase, and inversion of the coupled lasers. These chimera states defy several of the previously established existence criteria. While chimera states in phase oscillators generally demand nonlocal coupling, large system sizes, and specially prepared initial conditions, we find chimera states that are stable for global coupling in a network of only four coupled lasers for random initial conditions. The existence is linked to a regime of multistability between the synchronous steady state and asynchronous periodic solutions. We show that amplitude-phase coupling, a concept common in different fields, is necessary for the formation of the chimera states.

  6. Using CHIMERA detector at LNS for gamma-particle coincidences

    Cardella G.

    2016-01-01

    Full Text Available We have recently evaluated the quality of γ-ray angular distributions that can be extracted in particle-gamma coincidence measurements using the CHIMERA detector at LNS. γ-rays have been detected using the CsI(Tl detectors of the spherical part of the CHIMERA array. Very clean γ-rays angular distributions were extracted in reactions induced by different stable beams impinging on 12C thin targets. The results evidenced an effect of projectile spin flip on the γ-rays angular distributions. γ-particle coincidence measurements were also performed in reactions induced by neutron rich exotic beams produced through in-flight fragmentation at LNS. In recent experiments also the Farcos array was used to improve energy and angular resolution measurements of the detected charged particles. Results obtained with both stable and radioactive beams are reported.

  7. Metastable Chimera States in Community-Structured Oscillator Networks

    Shanahan, Murray

    2010-01-01

    A system of symmetrically coupled identical oscillators with phase lag is presented, which is capable of generating a large repertoire of transient (metastable) "chimera" states in which synchronisation and desynchronisation co-exist. The oscillators are organised into communities, such that each oscillator is connected to all its peers in the same community and to a subset of the oscillators in other communities. Measures are introduced for quantifying metastability, the prevalence of chimera states, and the variety of such states a system generates. By simulation, it is shown that each of these measures is maximised when the phase lag of the model is close, but not equal, to pi/2. The relevance of the model to a number of fields is briefly discussed, with particular emphasis on brain dynamics.

  8. Using CHIMERA detector at LNS for gamma-particle coincidences

    Cardella, G.; Acosta, L.; Auditore, L.; Chatterjiee, M. B.; Castoldi, A.; De Filippo, E.; Dell'Aquila, D.; De Luca, S.; Gnoffo, B.; Guazzoni, C.; Francalanza, L.; Lanzalone, G.; Lombardo, I.; Martorana, N.; Norella, S.; Pagano, A.; Pagano, E. V.; Papa, M.; Pirrone, S.; Politi, G.; Quattrocchi, L.; Rizzo, F.; Russotto, P.; Trifirò, A.; Trimarchi, M.; Verde, G.; Vigilante, M.

    2016-05-01

    We have recently evaluated the quality of γ-ray angular distributions that can be extracted in particle-gamma coincidence measurements using the CHIMERA detector at LNS. γ-rays have been detected using the CsI(Tl) detectors of the spherical part of the CHIMERA array. Very clean γ-rays angular distributions were extracted in reactions induced by different stable beams impinging on 12C thin targets. The results evidenced an effect of projectile spin flip on the γ-rays angular distributions. γ-particle coincidence measurements were also performed in reactions induced by neutron rich exotic beams produced through in-flight fragmentation at LNS. In recent experiments also the Farcos array was used to improve energy and angular resolution measurements of the detected charged particles. Results obtained with both stable and radioactive beams are reported.

  9. Origin of hemopoietic stromal progenitor cells in chimeras

    Intravenously injected bone marrow cells do not participate in the regeneration of hemopoietic stromal progenitors in irradiated mice, nor in the curetted parts of the recipient's marrow. The hemopoietic stromal progenitors in allogeneic chimeras are of recipient origin. The adherent cell layer (ACL) of long-term cultures of allogeneic chimera bone marrow contains only recipient hemopoietic stromal progenitors. However, in ectopic hemopoietic foci produced by marrow implantation under the renal capsule and repopulated by the recipient hemopoietic cells after irradiation and reconstitution by syngeneic hemopoietic cells, the stromal progenitors were of implant donor origin, as were stromal progenitors of the ACL in long-term cultures of hemopoietic cells from ectopic foci. Our results confirm that the stromal and hemopoietic progenitors differ in origin and that hemopoietic stromal progenitors are not transplantable by the intravenous route in mice

  10. The oscillating two-cluster chimera state in non-locally coupled phase oscillators

    Zhu, Yun; Li, Yuting; ZHANG, MEI; Yang, Junzhong

    2011-01-01

    We investigate an array of identical phase oscillators non-locally coupled without time delay, and find that chimera state with two coherent clusters exists which is only reported in delay-coupled systems previously. Moreover, we find that the chimera state is not stationary for any finite number of oscillators. The existence of the two-cluster chimera state and its time-dependent behaviors for finite number of oscillators are confirmed by the theoretical analysis based on the self-consistenc...

  11. Chimera states in networks of nonlocally coupled Hindmarsh-Rose neuron models

    Hizanidis, Johanne; Kanas, Vasilis; Bezerianos, Anastasios; Bountis, Tassos

    2013-01-01

    We have identified the occurrence of chimera states for various coupling schemes in networks of two-dimensional and three-dimensional Hindmarsh-Rose oscillators, which represent realistic models of neuronal ensembles. This result, together with recent studies on multiple chimera states in nonlocally coupled FitzHugh-Nagumo oscillators, provide strong evidence that the phenomenon of chimeras may indeed be relevant in neuroscience applications. Moreover, our work verifies the existence of chime...

  12. Experimental observation of chimera and cluster states in a minimal globally coupled network

    Hart, Joseph D.; Bansal, Kanika; Murphy, Thomas E.; Roy, Rajarshi

    2015-01-01

    A "chimera state" is a dynamical pattern that occurs in a network of coupled identical oscillators when the symmetry of the oscillator population is broken into synchronous and asynchronous parts. We report the experimental observation of chimera and cluster states in a network of four globally coupled chaotic opto-electronic oscillators. This is the minimal network that can support chimera states, and our study provides new insight into the fundamental mechanisms underlying their formation. ...

  13. The costs and benefits of being a chimera.

    Foster, Kevin R.; Fortunato, Angelo; Strassmann, Joan E.; Queller, David C

    2002-01-01

    Most multicellular organisms are uniclonal. This is hypothesized to be because uniclonal organisms function better than chimeras (non-clonal organisms), owing to reduced levels of internal genetic conflict. We tested this idea using the social amoeba or slime mold Dictyostelium discoideum. When starving, the normally solitary amoebae aggregate to form a differentiated multicellular slug that migrates towards light and forms a fruiting body, facilitating the dispersal of spores. We added 10(7)...

  14. Production of Interspecific Germline Chimeras via Embryo Replacement.

    Choi, Hee Jung; Lee, Hyung Chul; Kang, Kyung Soo; Lee, Hyo Gun; Ono, Tamao; Nagai, Hiroki; Sheng, Guojun; Han, Jae Yong

    2015-08-01

    In avian species, primordial germ cells (PGCs) use the vascular system to reach their destination, the genital ridge. Because of this unique migratory route of avian germ cells, germline chimera production can be achieved via germ cell transfer into a blood vessel. This study was performed to establish an alternative germ cell-transfer system for producing germline chimeras by replacing an original host embryo with a donor embryo, while retaining the host extraembryonic tissue and yolk, before circulation. First, to test the migratory capacity of PGCs after embryo replacement, Korean Oge (KO) chick embryos were used to replace GFP transgenic chick embryos. Four days after replacement, GFP-positive cells were detected in the replaced KO embryonic gonads, and genomic DNA PCR analysis with the embryonic gonads demonstrated the presence of the GFP transgene. To produce an interspecific germline chimera, the original chick embryo proper was replaced with a quail embryo onto the chick yolk. To detect the gonadal PGCs in the 5.5-day-old embryonic gonads, immunohistochemistry was performed with monoclonal antibodies specific to either quail or chick PGCs, i.e., QCR1 and anti-stage-specific embryonic antigen-1 (SSEA-1), respectively. Both the QCR1-positive and SSEA-1-positive cells were detected in the gonads of replaced quail embryos. Forty percent of the PGC population in the quail embryos was occupied by chick extraembryonically derived PGCs. In conclusion, replacement of an embryo onto the host yolk before circulation can be applied to produce interspecies germline chimeras, and this germ cell-transfer technology is potentially applicable for reproduction of wild or endangered bird species. PMID:26063873

  15. Tolerance, immunocompetence, and secondary disease in fully allogeneic radiation chimeras

    The aim of this study was to ascertain the extent to which secondary disease and mortality in fully allogeneic chimeras (C57BL leads to CBA) is caused (if at all) by a delayed graft-versus-host reaction. Adult CBA males were thymectomized, irradiated, and reconstituted with T-lymphocyte-depleted C57BL or CBA bone marrow cells (BMC), followed three weeks after irradiation by implantation under the kidney capsule of thymic lobes from C57BL or CBA fetal or adult donors. These mice were observed for the development of secondary disease for periods in excess of 250 days, and they were examined at 5 weeks or 4 months for T lymphocyte reactivity and tolerance to alloantigens, using the cell-mediated lympholysis assay (CML). The following results were obtained. First, removal of T lymphocytes with anti-Thy 1 antibody and complement from allogeneic bone marrow did not prevent wasting and eventual death, although it prolonged the lifespan of mice substantially. Second, T lymphocytes generated from bone marrow-derived precursor cells became tolerant of the histocompatibility antigens of the thymus donor strain but remained normally reactive to third-party antigens. Third, allogeneic radiation chimeras did not survive as well as animals reconstituted with syngeneic cells, even when they were demonstrably tolerant in CML. Fourth, C57BL BMC maturing in a CBA host equipped with a C57BL thymus graft did not become tolerant of host antigens, indicating that extra-thymic tolerance does not occur in fully allogeneic--as opposed to semiallogeneic--chimeras. It is argued that the function of B lymphocytes and/or accessory cells is impaired in fully allogeneic radiation chimeras, and that the mortality observed was directly related to the resulting immunodeficiency. The relevance of the results described in this paper to clinical bone marrow transplantation is discussed

  16. Icing modelling in NSMB with chimera overset grids

    Pena, D. [Ècole Polytechnique de Montréal (Canada); ICUBE, Strasbourg University (France); Deloze, T.; Laurendeau, E. [Ècole Polytechnique de Montréal (Canada); Hoarau, Y. [ICUBE, Strasbourg University (France)

    2015-03-10

    In aerospace Engineering, the accurate simulation of ice accretion is a key element to increase flight safety and avoid accidents related to icing effects. The icing code developed in the NSMB solver is based on an Eulerian formulation for droplets tracking, an iterative Messinger model using a modified water runback scheme for ice thickness calculation and mesh deformation to track the ice/air interface through time. The whole process is parallelized with MPI and applied with chimera grids.

  17. Radiobiological research on carnation chimerae Dianthus Caryophyllus L

    A radiobiological study of periclinal carnation chimerae is carried out by subjecting whole plants and cuttings at different physiological stages to cobalt 60 gamma radiation under different dose and dose rate conditions. The effects of these treatments are observed during cultivation of the treated plants and by microscopic examination of irradiated meristem sections. The destruction of meristem cells in proportions varying with the irradiation conditions leads to structural changes in the chimerae; the more frequent change is the formation of genetically homogeneous stalks from different genotypes existing in the irradiated plant. Treatment by ionizing radiations is thus a practical means of detecting periclinical chimerae which, as in the case of carnations, are very common in plants grown by vegetative propagation. However since more than two independent meristem cell groups are usually present it is not possible by this method alone to define the distribution of the differentent genotypes in these groups; additional genetic studies or cell labelling such as chlorophyll or genoma mutations are then necessary

  18. Chimeras, moral status, and public policy: implications of the abortion debate for public policy on human/nonhuman chimera research.

    Streiffer, Robert

    2010-01-01

    Researchers are increasingly interested in creating chimeras by transplanting human embryonic stem cells (hESCs) into animals early in development. One concern is that such research could confer upon an animal the moral status of a normal human adult but then impermissibly fail to accord it the protections it merits in virtue of its enhanced moral status. Understanding the public policy implications of this ethical conclusion, though, is complicated by the fact that claims about moral status cannot play an unfettered role in public policy. Arguments like those employed in the abortion debate for the conclusion that abortion should be legally permissible even if abortion is not morally permissible also support, to a more limited degree, a liberal policy on hESC research involving the creation of chimeras. PMID:20579247

  19. Deficiency in early development of the thymus-dependent cells in irradiation chimeras attributable to recipient's environment

    Bone marrow chimeras were prepared using reciprocal combinations of AKR and C3H mice. When C3H mice were recipients, the number of thymocytes recoverable from such chimeras (C3H recipient chimeras) was small as compared with that from chimeras for which AKR mice were used as recipients (AKR recipient chimeras) regardless of donor strain. The thymocytes from C3H recipient chimeras showed a profound deficiency in generating proliferative responses to stimulation by anti-CD3 mAb (2C11) or anti-TCR (alpha, beta) mAb (H57-597), even though the expression of CD3 and TCR molecules fell within the same range as that in AKR recipient chimeras. Furthermore, after stimulation with immobilized 2C11, the proportion of IL-2R+ cells in the thymocytes from C3H recipient chimeras was much less than that in AKR recipient chimeras. However, no significant difference in proliferative responses to 2C11 plus PMA, in influx of Ca2+ after stimulation with 2C11 or IL-2 production in response to 2C11 plus PMA or PMA plus A23187 was demonstrated between C3H and AKR recipient chimeras. These findings suggest that the thymocytes from C3H recipient chimeras have a deficiency in the signal transduction system as compared with chimeras for which AKR mice are the recipients. The thymic stromal component involved in this difference in the C3H recipient chimeras is discussed

  20. Construction of eSRK Chimeras and Interaction between eSRK Chimeras and SCRs from Brassica oleracea L.%甘蓝eSRK重组体的构建及其与SCR的相互作用

    韦静宜; 高启国; 任雪松; 王小佳; 李成琼; 宋明

    2012-01-01

    SRK与SCR是甘蓝自交不亲和雌雄性决定因子,两者间相互作具有单倍型特异性.为了探讨HVⅠ/Ⅱ区域在SRK单倍型特异性及其与SCR互作中的作用,采用重组技术构建甘蓝不同单倍型eSRK (SRKE与SRKF)间的重组体eSRKE-1、eSRKE-2和eSRKE-3,用酵母双杂交系统3检测各eSRK重组体与SCR之间的相互作用.结果表明:SCRE能与eSRKE作用,而不能与eSRKF作用,说明eSRKE、eSRKF属于不同单倍型;SCRE与重组体eSRKE-1、eSRKE-2、eSRKE-3均不发生作用,HVⅠ和HVⅡ区域内差异的氨基酸位点共同参与了与SCR的作用;SCRF不能与eSRKE-1、eSRKE-2、eSRKE-3作用,替换HVⅠ/Ⅱ区域后并不能改变SRK的单倍型.%Self-incompatibility in Brassica is mediated by allele-specific interactions between stigma-expressed 5-locus receptor kinase (SRK) and pollen coat-localized 5-locus cysteinerich (SCR) ligands encoded by the 5-locus haplotype. To identify amino acid fragments within the SRK extracellular domain (eSRK) that are required for ligand-selective activation, we constructed chi-meric eSRK between two 5-locus haplotypes in Brassica oleracea, and identified the interaction between eSRK chimeras and SCRs by yeast two-hybrid system. The results showed that SRKE (not chimera) could interact with SCRE, and SRKF could interact with SCRF. All of eSRK chimeras could not interact with SCRs. The hypervariable regions, HVI and HVII, were essential for specificity in the SRK-SCR interaction. However, eSRK chimeras could not interact with SCRp, although they contained hypervariable regions come from eSRKp, which should be related with the overall sequence or 3D conformation of the segments determining SI specificity.

  1. Bio-inspired Silicification of Silica-binding Peptide-Silk Protein Chimeras: Comparison of Chemically and Genetically Produced Proteins

    Canabady-Rochelle, Laetitia L.S.; Belton, David J.; Deschaume, Olivier; Currie, Heather A.; Kaplan, David L; Perry, Carole C.

    2012-01-01

    Novel protein chimeras constituted of ‘silk’ and a silica-binding peptide (KSLSRHDHIHHH) were synthesized by genetic or chemical approaches and their influence on silica-silk based chimera composite formation evaluated. Genetic chimeras were constructed from 6 or 15 repeats of the 32 amino acid consensus sequence of Nephila clavipes spider silk ([SGRGGLGGQG AGAAAAAGGA GQGGYGGLGSQG]n) to which one silica binding peptide was fused at the N terminus. For the chemical chimera, 25 equivalents of t...

  2. Advances in Chimera Grid Tools for Multi-Body Dynamics Simulations and Script Creation

    Chan, William M.

    2004-01-01

    This viewgraph presentation contains information about (1) Framework for multi-body dynamics - Geometry Manipulation Protocol (GMP), (2) Simulation procedure using Chimera Grid Tools (CGT) and OVERFLOW-2 (3) Further recent developments in Chimera Grid Tools OVERGRID, Grid modules, Script library and (4) Future work.

  3. Characteristic distribution of finite-time Lyapunov exponents for chimera states.

    Botha, André E

    2016-01-01

    Our fascination with chimera states stems partially from the somewhat paradoxical, yet fundamental trait of identical, and identically coupled, oscillators to split into spatially separated, coherently and incoherently oscillating groups. While the list of systems for which various types of chimeras have already been detected continues to grow, there is a corresponding increase in the number of mathematical analyses aimed at elucidating the fundamental reasons for this surprising behaviour. Based on the model systems, there are strong indications that chimera states may generally be ubiquitous in naturally occurring systems containing large numbers of coupled oscillators - certain biological systems and high-Tc superconducting materials, for example. In this work we suggest a new way of detecting and characterising chimera states. Specifically, it is shown that the probability densities of finite-time Lyapunov exponents, corresponding to chimera states, have a definite characteristic shape. Such distributions could be used as signatures of chimera states, particularly in systems for which the phases of all the oscillators cannot be measured directly. For such cases, we suggest that chimera states could perhaps be detected by reconstructing the characteristic distribution via standard embedding techniques, thus making it possible to detect chimera states in systems where they could otherwise exist unnoticed. PMID:27374473

  4. Mechanisms of tolerance in murine radiation bone marrow chimeras. I. Nonspecific suppression of alloreactivity by spleen cells from early, but not late, chimeras

    Allogeneic chimeras were prepared using lethally irradiated B6 hosts and untreated marrow from exsanguinated BALB/c donors. For about two months after reconstitution, chimeras had very weak antihost cell-mediated lymphocytotoxicity (CML) reactivity and little third-party alloreactivity. During this time a cell population capable of suppressing CML reactivity against both host and third-party alloantigens (i.e., antigen-nonspecific) was demonstrated in chimera spleens by in vitro mixing experiments. The putative suppressor cells were Thy-1-negative and radiation-sensitive. Subsequently, mature chimeras showed host tolerance and strong third-party alloreactivity. At this point suppressor mechanisms could no longer be demonstrated. These data are consistent with a clonal elimination hypothesis in that they do not provide evidence to indicate that maintenance of specific immune tolerance is mediated by an active suppressor mechanism

  5. Infusion of donor lymphocytes into stable canine radiation chimeras: implications for mechanism of transplantation tolerance

    Canine radiation chimeras were used to investigate further mechanism(s) responsible for maintaining the stable chimeric state. In an attempt to elucidate the nature of this postulated active mechanism, the cytotoxicity of donor lymphocytes for fibroblasts of the chimera and the presence or absence of serum-blocking factors were assessed in vitro by using a cellular inhibition (CI) assay. The presence of serum-blocking factors did not protect against the development of significant GVHD in two chimeras (fatal in one). GVHD did not occur in four other chimeras after infusion of cytotoxic donor lymphocytes despite the absence of serum-blocking factors. These and previous results suggest that serum-blocking factors are not the mechanism suppressing the development of GVHD in canine radiation chimeras, and raise the possibility that a suppressor cell population may be responsible for preventing GVHD

  6. Chaotic weak chimeras and their persistence in coupled populations of phase oscillators

    Bick, Christian; Ashwin, Peter

    2016-05-01

    Nontrivial collective behavior may emerge from the interactive dynamics of many oscillatory units. Chimera states are chaotic patterns of spatially localized coherent and incoherent oscillations. The recently-introduced notion of a weak chimera gives a rigorously testable characterization of chimera states for finite-dimensional phase oscillator networks. In this paper we give some persistence results for dynamically invariant sets under perturbations and apply them to coupled populations of phase oscillators with generalized coupling. In contrast to the weak chimeras with nonpositive maximal Lyapunov exponents constructed so far, we show that weak chimeras that are chaotic can exist in the limit of vanishing coupling between coupled populations of phase oscillators. We present numerical evidence that positive Lyapunov exponents can persist for a positive measure set of this inter-population coupling strength.

  7. Pharmacological profile of the 5-HT-induced inhibition of cardioaccelerator sympathetic outflow in pithed rats: correlation with 5-HT1 and putative 5-ht5A/5B receptors.

    Sánchez-Lopez, Araceli; Centurión, David; Vázquez, Erika; Arulmani, Udayasankar; Saxena, Pramod R; Villalón, Carlos M

    2003-10-01

    Continuous infusions of 5-hydroxytryptamine (5-HT) inhibit the tachycardiac responses to preganglionic (C7-T1) sympathetic stimulation in pithed rats pretreated with desipramine. The present study identified the pharmacological profile of this inhibitory action of 5-HT. The inhibition induced by intravenous (i.v.) continuous infusions of 5-HT (5.6 microg x kg-1x min-1) on sympathetically induced tachycardiac responses remained unaltered after i.v. treatment with saline or the antagonists GR 127935 (5-HT1B/1D), the combination of WAY 100635 (5-HT1A) plus GR 127935, ritanserin (5-HT2), tropisetron (5-HT3/4), LY215840 (5-HT7) or a cocktail of antagonists/inhibitors consisting of yohimbine (alpha2), prazosin (alpha1), ritanserin, GR 127935, WAY 100635 and indomethacin (cyclooxygenase), but was abolished by methiothepin (5-HT1/2/6/7 and recombinant 5-ht5A/5B). These drugs, used in doses high enough to block their respective receptors/mechanisms, did not modify the sympathetically induced tachycardiac responses per se. I.v. continuous infusions of the agonists 5-carboxamidotryptamine (5-CT; 5-HT1/7 and recombinant 5-ht5A/5B), CP 93129 (r5-HT1B), sumatriptan (5-HT1B/1D), PNU-142633 (5-HT1D) and ergotamine (5-HT1B/1D and recombinant 5-ht5A/5B) mimicked the above sympatho-inhibition to 5-HT. In contrast, the agonists indorenate (5-HT1A) and LY344864 (5-ht1F) were inactive. Interestingly, 5-CT-induced cardiac sympatho-inhibition was abolished by methiothepin, the cocktail of antagonists/inhibitors, GR 127935 or the combination of SB224289 (5-HT1B) plus BRL15572 (5-HT1D), but remained unchanged when SB224289 or BRL15572 were given separately. Therefore, 5-HT-induced cardiac sympatho-inhibition, being unrelated to 5-HT2, 5-HT3, 5-HT4, 5-ht6, 5-HT7 receptors, alpha1/2-adrenoceptor or prostaglandin synthesis, seems to be primarily mediated by (i). 5-HT1 (probably 5-HT1B/1D) receptors and (ii). a novel mechanism antagonized by methiothepin that, most likely, involves putative 5

  8. Study on proliferative responses to host Ia antigens in allogeneic bone marrow chimera in mice: sequential analysis of the reactivity and characterization of the cells involved in the responses

    Irradiation bone marrow chimeras were established by reconstitution of lethally irradiated AKR mice with C57BL/10 marrow cells to permit serial analysis of the developing reactivities of lymphocytes from such chimeras, [B10----AKR], against donor, host, or third party antigens. We found that substantial proliferative responses to Ia antigens of the recipient strain and also to third party antigens were generated by the thymocytes obtained from the irradiation chimeras at an early stage after bone marrow reconstitution. The majority of the responding thymocytes had surfaces lacking demonstrable peanut agglutinin receptors and were donor type Thy-1+, Ly-2-, and L3T4+ in both anti-recipient and anti-third party MLR. In anti-host responses, however, Ly-2+ thymocytes seemed to be at least partially involved. This capacity of thymus cells to mount a response to antigens of the recipient strain declined shortly thereafter, whereas the capacity to mount MLR against third party antigens persisted. The spleen cells of [B10----AKR] chimeras at the same time developed a more durable capability to exhibit anti-host reactivities and a permanent capability of reacting to third party allo-antigens. The stimulator antigens were Ia molecules on the stimulator cells in both anti-recipient and anti-third party MLR. The responding splenocytes were of donor origin and most of them had Thy-1+, Ly-1+2-, and L3T4+ phenotype

  9. Complement Receptors C5aR and C5L2 Are Associated with Metabolic Profile, Sex Hormones, and Liver Enzymes in Obese Women Pre- and Postbariatric Surgery

    Reza Rezvani

    2014-01-01

    Full Text Available Objective. Obesity is associated with metabolic dysfunction with sex differences and chronic, low-grade inflammation. We proposed that hepatic expression of immune complement C3 related receptors (C3aR, C5aR, and C5L2 would be associated with pre- or postmenopausal status and metabolic profile in severely obese women. We hypothesized that C5L2/C5aR ratio, potentially influencing the ASP/C5L2 metabolic versus C5a/C5aR immune response, would predict metabolic profiles after weight loss surgery. Materials and Methods. Fasting plasma (hormone, lipid, and enzyme analysis and liver biopsies (RT-PCR gene expression were obtained from 91 women during surgery. Results. Hepatic C5L2 mRNA expression was elevated in pre- versus postmenopausal women (P<0.01 and correlated positively with circulating estradiol, estrone, ApoB, ApoA1, ApoA1/B, waist circumference, age, and LDL-C (all P<0.05. While plasma ASP was lower in pre- versus postmenopausal women (P<0.01, the hepatic C5L2/C5aR mRNA ratio was increased (P<0.001 and correlated positively with estrone (P<0.01 and estradiol (P<0.001 and negatively with circulating ApoB and liver enzymes ALT, AST, and GGT (all P<0.05. Over 12 months postoperatively, liver enzymes in low C5L2/C5aR mRNA ratio group remained higher (ALP and ALT, P<0.05, AST and GGT, P<0.001 2-way-ANOVA. Conclusion. C5L2-C5aR association with other mediators including estrogens may contribute to hepatic metabolic and inflammatory function.

  10. Synthesis and SAR of Imidazo[1,5-a]pyridine derivatives as 5-HT4 receptor partial agonists for the treatment of cognitive disorders associated with Alzheimer's disease.

    Nirogi, Ramakrishna; Mohammed, Abdul Rasheed; Shinde, Anil K; Bogaraju, Narsimha; Gagginapalli, Shankar Reddy; Ravella, Srinivasa Rao; Kota, Laxman; Bhyrapuneni, Gopinadh; Muddana, Nageswara Rao; Benade, Vijay; Palacharla, Raghava Chowdary; Jayarajan, Pradeep; Subramanian, Ramkumar; Goyal, Vinod Kumar

    2015-10-20

    Alzheimer's disease (AD) is a neurodegenerative disease which has a higher prevalence and incidence in older people. The need for improved AD therapies is unmet. The 5-hydroxytryptamine4 receptor (5-HT4R) partial agonists may be of benefit for both the symptomatic and disease-modifying treatment of cognitive disorders associated with AD. Herein, we report the design, synthesis and SAR of imidazo[1,5-a] pyridine derivatives as 5-HT4R partial agonists. The focused SAR, optimization of ADME properties resulted the discovery of compound 5a as potent, selective, brain penetrant 5-HT4 partial agonist as a lead compound with good ADME properties and efficacy in both symptomatic and disease modifying animal models of cognition. PMID:26363507

  11. Structural basis of LaDR5, a novel agonistic anti-death receptor 5 (DR5 monoclonal antibody, to inhibit DR5/TRAIL complex formation

    Qiao Chunxia

    2012-07-01

    Full Text Available Abstract Background As a member of the TNF superfamily, TRAIL could induce human tumor cell apoptosis through its cognate death receptors DR4 or DR5, which can induce formation of the death inducing signaling complex (DISC and activation of the membrane proximal caspases (caspase-8 or caspase-10 and mitochondrial pathway. Some monoclonal antibodies against DR4 or DR5 have been reported to have anti-tumor activity. Results In this study, we reported a novel mouse anti-human DR5 monoclonal antibody, named as LaDR5, which could compete with TRAIL to bind DR5 and induce the apoptosis of Jurkat cells in the absence of second cross-linking in vitro. Using computer-guided molecular modeling method, the 3-D structure of LaDR5 Fv fragment was constructed. According to the crystal structure of DR5, the 3-D complex structure of DR5 and LaDR5 was modeled using molecular docking method. Based on distance geometry method and intermolecular hydrogen bonding analysis, the key functional domain in DR5 was predicted and the DR5 mutants were designed. And then, three mutants of DR5 was expressed in prokaryotic system and purified by affinity chromatograph to determine the epitope of DR5 identified by LaDR5, which was consistent with the theoretical results of computer-aided analysis. Conclusions Our results demonstrated the specific epitope located in DR5 that plays a crucial role in antibody binding and even antineoplastic bioactivity. Meanwhile, revealed structural features of DR5 may be important to design or screen novel drugs agonist DR5.

  12. β-Catenin-dependent pathway activation by both promiscuous "canonical" WNT3a-, and specific "noncanonical" WNT4- and WNT5a-FZD receptor combinations with strong differences in LRP5 and LRP6 dependency.

    Ring, Larisa; Neth, Peter; Weber, Christian; Steffens, Sabine; Faussner, Alexander

    2014-02-01

    The WNT/β-catenin signalling cascade is the best-investigated frizzled receptor (FZD) pathway, however, whether and how specific combinations of WNT/FZD and co-receptors LRP5 and LRP6 differentially affect this pathway are not well understood. This is mostly due to the fact that there are 19 WNTs, 10 FZDs and at least two co-receptors. In our attempt to identify the signalling capabilities of specific WNT/FZD/LRP combinations we made use of our previously reported TCF/LEF Gaussia luciferase reporter gene HEK293 cell line (Ring et al., 2011). Generation of WNT/FZD fusion constructs - but not their separate transfection - without or with additional isogenic overexpression of LRP5 and LRP6 in our reporter cells permitted the investigation of specific WNT/FZD/LRP combinations. The canonical WNT3a in fusion to almost all FZDs was able to induce β-catenin-dependent signalling with strong dependency on LRP6 but not LRP5. Interestingly, noncanonical WNT ligands, WNT4 and WNT5a, were also able to act "canonically" but only in fusion with specific FZDs and with selective dependence on LRP5 or LRP6. These data and extension of this experimental setup to the poorly characterized other WNTs should facilitate deeper insight into the complex WNT/FZD signalling system and its function. PMID:24269653

  13. MODELS FOR MOUSE CHIMERA PRODUCTION: AGGREGATION OF ES CELLS WITH CLEAVAGE STAGE EMBRYOS

    STANCA CLAUDIA

    2007-01-01

    Full Text Available In a mutant ES cells↔ wild-type embryo chimera, ES cells behave more like epiblastcells. They can contribute to the primitive ectoderm layers, which give rise to all theembryonic tissues and some extraembryonic tissues (Beddington and Robertson,1989, but not to trophectoderm or primitive endoderm. Using transgenic ES celllines, aggregated with cleavage stage host embryo, ES cells can integrate randomlyin the embryo proper. If they will be take part in the formation of ICM (inner cellmass, it will be possible to obtain germline chimera animals. To generate ES cells↔ cleavage stage host embryo chimeras, we used (CD-1 mice as donors of hostembryos as well as recipients of manipulated embryos. For chimera production, weused fluorescent-labeled ES cell line (CD1/EGFP, because in this case we canfollow the fate of ES cells during the embryonic development. We produced thechimers using “aggregation chimera technique”. 8 cells stage zona pellucida free,mouse embryos were aggregated in an aggregation plates, with a clump of ES cells(10 – 15 cells. The chimera embryos were cultivated for 24 hours in the incubator(at 37 °C, 5% CO2 in air. The chimera blastocysts resulted after cultivation, weretransferred to the uterus of the 2.5-dpc pseudo pregnant females.

  14. receptores

    Salete Regina Daronco Benetti

    2006-01-01

    Full Text Available Se trata de un estudio etnográfico, que tuvo lo objetivo de interpretar el sistema de conocimiento y del significado atribuidos a la sangre referente a la transfusión sanguínea por los donadores y receptores de un banco de sangre. Para la colecta de las informaciones se observaron los participantes y la entrevista etnográfica se realizó el análisis de dominio, taxonómicos y temáticos. Los dominios culturales fueron: la sangre es vida: fuente de vida y alimento valioso; creencias religiosas: fuentes simbólicas de apoyos; donación sanguínea: un gesto colaborador que exige cuidarse, gratifica y trae felicidad; donación sanguínea: fuente simbólica de inseguridad; estar enfermo es una condición para realizar transfusión sanguínea; transfusión sanguínea: esperanza de vida; Creencias populares: transfusión sanguínea como riesgo para la salud; donadores de sangre: personas benditas; donar y recibir sangre: como significado de felicidad. Temática: “líquido precioso que origina, sostiene, modifica la vida, provoca miedo e inseguridad”.

  15. A chimera embryo assay reveals a decrease in embryonic cellular proliferation induced by sperm from X-irradiated male mice

    Male mice were divided into three experimental groups and a control group. Mice in the experimental groups received one of three doses of acute X irradiation (1.73, 0.29, and 0.05 Gy) and together with the control unirradiated mice were then mated weekly to unirradiated female mice for a 9-week experimental period. Embryos were recovered from the weekly matings at the four-cell stage and examined by the chimera assay for proliferative disadvantage. Aggregation chimeras were constructed of embryos from female mice mated to irradiated males (experimental embryos) and embryos from females mated to unexposed males (control embryos) and contained either one experimental embryo and one control embryo (heterologous chimera) or two control embryos (control chimera). The control embryo in heterologous chimeras and either embryo in control chimeras were prelabeled with the vital dye fluorescein isothiocyanate (FITC), and the chimeras were cultured for 40 h and viewed under phase-contrast and epifluorescence microscopy to obtain total embryo cell number and the cellular contribution from the FITC-labeled embryo. Experimental and control embryos that were cultured singly were also examined for embryo cell number at the end of the 40-h culture period. In control chimeras, the mean ratio of the unlabeled cells:total chimera cell number (henceforth referred to as ''mean ratio'') was 0.50 with little or no weekly variation over the 9-week experimental period. During Weeks 4-7, the mean ratios of heterologous chimeras differed significantly from the mean ratio of control chimeras with the greatest differences occurring during Week 7 (0.41 for chimeras of 0.05 Gy dose group, 0.40 for chimeras of the 0.29 Gy dose group, and 0.17 for chimeras of the 1.73 Gy dose group)

  16. Protein-DNA chimeras: synthesis of two-arm chimeras and non-mechanical effects of the DNA spring

    DNA molecular springs have recently been used to control the activity of enzymes and ribozymes. In this approach, the mechanical stress exerted by the molecular spring alters the enzyme's conformation and thus the enzymatic activity. Here we describe a method alternative to our previous one to attach DNA molecular springs to proteins, where two separate DNA 'arms' are coupled to the protein and subsequently ligated. We report certain non-mechanical effects associated with the DNA spring observed in some chimeras with specific DNA sequences and the nucleotide binding enzyme guanylate kinase. If a ssDNA 'arm' is attached to the protein by one end only, we find that in some cases (depending on the DNA sequence and attachment point on the protein's surface) the unhybridized DNA arm inhibits the enzyme, while hybridization of the DNA arm leads to an apparent activation of the enzyme. One interpretation is that, in these cases, hybridization of the DNA arm removes it from the vicinity of the active site of the enzyme. We show how mechanical and non-mechanical effects of the DNA spring can be distinguished. This is important if one wants to use the protein-DNA chimeras to quantitatively study the response of the enzyme to mechanical perturbations.

  17. Pharmacological characterisation of strychnine and brucine analogues at glycine and alpha7 nicotinic acetylcholine receptors

    Jensen, Anders A.; Gharagozloo, Parviz; Birdsall, Nigel J M;

    2006-01-01

    of tertiary and quaternary analogues as well as bisquaternary dimers of strychnine and brucine at human alpha1 and alpha1beta glycine receptors and at a chimera consisting of the amino-terminal domain of the alpha7 nicotinic receptor (containing the orthosteric ligand binding site) and the ion...... profiles of strychnine and brucine, none of the analogues displayed significant selectivity between the alpha1 and alpha1beta subtypes. The structure-activity relationships for the compounds at the alpha7/5-HT3 chimera were significantly different from those at the glycine receptors. Most strikingly......, quaternization of strychnine and brucine with substituents possessing different steric and electronic properties completely eliminated the activity at the glycine receptors, whereas binding affinity to the alpha7/5-HT3 chimera was retained for the majority of the quaternary analogues. This study provides an...

  18. Clonal deletion: A mechanism of tolerance in mixed bone marrow chimeras

    The mechanism of antigen-specific immunologic unresponsiveness which results from lethal irradiation and mixed (syngeneic-allogeneic) bone marrow cell (BMC) reconstitution is unknown. To determine whether clonal deletion is the mechanism of tolerance in this model, monoclonal antibody (Mab) RR-4-4, specific for a T-cell receptor (V beta 6) reactive against the minor alloantigen MLsa, was employed. Six-week-old B10 mice (H-2b, Mlsb, Thyl.2) were tolerized to AKR antigens (H-2k, Mlsa, Thyl.1) by whole body irradiation (950 R) and iv infusion of T-cell-depleted (TCD) B10 BMC + non-TCD AKR BMC. Chimerism and antigen-specific tolerance were documented by flow microfluorometry (FMF), skin grafting, mixed lymphocyte reaction, and cell-mediated lympholysis. When tolerant B10 mice (n = 15) had accepted AKR skin grafts for greater than 100 days, these animals were studied for the presence of host V beta 6+ T cells using Mab RR-4-4. FMF revealed that 0-5% of host (B10) lymph node and spleen cells from chimeras were V beta 6+ while 15-20% of lymph node and spleen cells from control B10 mice expressed V beta 6. These data demonstrate that clonal deletion occurs in the lethal irradiation-mixed reconstitution model as evidenced by the near total elimination of Mlsa-reactive V beta 6+ T cells and suggest that it maybe a mechanism responsible for tolerance in adult mice

  19. Chimeras in a network of three oscillator populations with varying network topology

    Martens, Erik Andreas

    2010-01-01

    system as a model system, we discuss for the first time the influence of network topology on the existence of so-called chimera states. In this context, the network with three populations represents an interesting case because the populations may either be connected as a triangle, or as a chain, thereby......-like. By showing that chimera states only exist for a bounded set of parameter values, we demonstrate that their existence depends strongly on the underlying network structures, and conclude that chimeras exist on networks with a chain-like character....

  20. Immune responsiveness and incidence of reticulum cell sarcoma in long-term syngeneic radiation chimeras

    Long-term syngeneic radiation chimeras displayed a very low incidence of reticulum cell sarcoma as compared with control mice. Immune reactivity of these animals was studied in vivo by anti-dinitrophenyl antibody titer and affinity and in vitro by mitotic responsiveness to phytohemagglutinin, concanavalin A and lipopolysaccharide. Antibody titer and affinity as well as the response to T lectins were found to be increased in chimeras. These results were attributed to increased function of mature T2 cells, which could explain the reduced incidence of reticulum cell sarcoma in chimeras

  1. Present status of the Chimera-Isospin experiment

    The CHIMERA detector was designed to significantly contribute to multifragmentation studies in the field of heavy ion collisions at intermediate energies. The device has been used at 'Laboratori Nazionali del Sud' (LNS) in Catania (Italy) to study different aspects of the relevant nuclear reaction mechanism, in two different campaigns: the first one in 2000, by using the forward part (1 - 30 degrees) of the device, and the second one in 2003, by using the 4π geometry. The experimental results have confirmed the capability of the apparatus for good isotopic identification of light charged particles and light fragments (3< Z<10) in a wide angular detection range. The data analysis relative to the first 2000 campaign (REVERSE) is presently aimed to disentangle dynamical and equilibrium emission components in multifragmentation reactions and to learn more about the role of the isospin degree of freedom in asymmetric nuclear matter. Reduction of the data of the second campaign is still in progress. (authors)

  2. Linked and knotted chimera filaments in oscillatory systems

    Lau, Hon Wai; Davidsen, Jörn

    2016-07-01

    While the existence of stable knotted and linked vortex lines has been established in many experimental and theoretical systems, their existence in oscillatory systems and systems with nonlocal coupling has remained elusive. Here, we present strong numerical evidence that stable knots and links such as trefoils and Hopf links do exist in simple, complex, and chaotic oscillatory systems if the coupling between the oscillators is neither too short ranged nor too long ranged. In this case, effective repulsive forces between vortex lines in knotted and linked structures stabilize curvature-driven shrinkage observed for single vortex rings. In contrast to real fluids and excitable media, the vortex lines correspond to scroll wave chimeras [synchronized scroll waves with spatially extended (tubelike) unsynchronized filaments], a prime example of spontaneous synchrony breaking in systems of identical oscillators. In the case of complex oscillatory systems, this leads to a topological superstructure combining knotted filaments and synchronization defect sheets.

  3. On applications of chimera grid schemes to store separation

    Cougherty, F. C.; Benek, J. A.; Steger, J. L.

    1985-01-01

    A finite difference scheme which uses multiple overset meshes to simulate the aerodynamics of aircraft/store interaction and store separation is described. In this chimera, or multiple mesh, scheme, a complex configuration is mapped using a major grid about the main component of the configuration, and minor overset meshes are used to map each additional component such as a store. As a first step in modeling the aerodynamics of store separation, two dimensional inviscid flow calculations were carried out in which one of the minor meshes is allowed to move with respect to the major grid. Solutions of calibrated two dimensional problems indicate that allowing one mesh to move with respect to another does not adversely affect the time accuracy of an unsteady solution. Steady, inviscid three dimensional computations demonstrate the capability to simulate complex configurations, including closely packed multiple bodies.

  4. Laser Chimeras as a paradigm for multi-stable patterns in complex systems

    Larger, Laurent; Maistrenko, Yuri

    2014-01-01

    Chimera is a rich and fascinating class of self-organized solutions developed in high dimensional networks having non-local and symmetry breaking coupling features. Its accurate understanding is expected to bring important insight in many phenomena observed in complex spatio-temporal dynamics, from living systems, brain operation principles, and even turbulence in hydrodynamics. In this article we report on a powerful and highly controllable experiment based on optoelectronic delayed feedback applied to a wavelength tunable semiconductor laser, with which a wide variety of Chimera patterns can be accurately investigated and interpreted. We uncover a cascade of higher order Chimeras as a pattern transition from N to N - 1 clusters of chaoticity. Finally, we follow visually, as the gain increases, how Chimera is gradually destroyed on the way to apparent turbulence-like system behaviour.

  5. Chimera states in systems of nonlocal nonidentical phase-coupled oscillators

    Xie, Jianbo; Kao, Hsien-Ching; Knobloch, Edgar

    2015-03-01

    Chimera states consisting of domains of coherently and incoherently oscillating nonlocally coupled phase oscillators in systems with spatial inhomogeneity are studied. The inhomogeneity is introduced through the dependence of the oscillator frequency on its location. Two types of spatial inhomogeneity, localized and spatially periodic, are considered and their effects on the existence and properties of multicluster and traveling chimera states are explored. The inhomogeneity is found to break up splay states, to pin the chimera states to specific locations, and to trap traveling chimeras. Many of these states can be studied by constructing an evolution equation for a complex order parameter. Solutions of this equation are in good agreement with the results of numerical simulations.

  6. Studies on the mechanism of stable graft--host tolerance in canine and human radiation chimeras

    In studies with dogs, marrow donors were immunized against their chimeras by repeated skin grafts which they rejected. Lymphocytes from chimeras and donors were tested for cell inhibition by exposure to skin fibroblasts from chimeras and donors. Results were not compatible with the concept that tolerance in radiation chimeras is maintained by serum-blocking factors. They provide circumstantial evidence against the possibility that the stable chimeric state is the result of the deletion of a close or inactivation of donor lymphocytes specifically responsive for host antigens. They are most consistent with the possibility that a suppressor-cell population is responsible for the maintenance of tolerance. Human recipients of marrow transplants were tested with the cell inhibition assay. Although the incidence of positive cell inhibition and blocking was somewhat higher than in the dog, results were not compatible with the concept that serum blocking is the sole mechanism for maintaining the stable chimeric state in human patients

  7. Status of T- and B-cell cooperation in radiation chimeras: evidence for a suppressor effect

    Absolute tolerance may not be in operation in the allogeneic bone marrow chimera, but rather a dynamic state involving interaction not only between the donor and host but also among the donor-lymphoid cells themselves may exist. Whether this observation made in one allogeneic chimera, CD2F1→ C3BF1, will be true for other chimeras (different strain combinations, species) remains to be shown. Thus, the tempo, mode, and requirement for the generation of suppressor T cells are factors that may vary for any specific allogeneic bone marrow transplant. Finally, the manner and degree to which the tolerance-inducing mechanism may affect T- and B-cell functions of the chimera with respect to third-party antigens are yet to be determined

  8. Chimera states in networks of phase oscillators: The case of two small populations

    Panaggio, Mark J.; Abrams, Daniel M.; Ashwin, Peter; Laing, Carlo R.

    2016-01-01

    Chimera states are dynamical patterns in networks of coupled oscillators in which regions of synchronous and asynchronous oscillation coexist. Although these states are typically observed in large ensembles of oscillators and analyzed in the continuum limit, chimeras may also occur in systems with finite (and small) numbers of oscillators. Focusing on networks of 2 N phase oscillators that are organized in two groups, we find that chimera states, corresponding to attracting periodic orbits, appear with as few as two oscillators per group and demonstrate that for N >2 the bifurcations that create them are analogous to those observed in the continuum limit. These findings suggest that chimeras, which bear striking similarities to dynamical patterns in nature, are observable and robust in small networks that are relevant to a variety of real-world systems.

  9. Robustness of chimera states for coupled FitzHugh-Nagumo oscillators

    Omelchenko, Iryna; Provata, Astero; Hizanidis, Johanne; Schoell, Eckehard; Hoevel, Philipp

    2014-01-01

    Chimera states are complex spatio-temporal patterns that consist of coexisting domains of spatially coherent and incoherent dynamics. This counterintuitive phenomenon was first observed in systems of identical oscillators with symmetric coupling topology. Can one overcome these limitations? To address this question, we discuss the robustness of chimera states in networks of FitzHugh-Nagumo oscillators. Considering networks of inhomogeneous elements with regular coupling topology, and networks...

  10. Chimera states: Coexistence of coherence and incoherence in networks of coupled oscillators

    Panaggio, Mark J; Abrams, Daniel M.

    2014-01-01

    A chimera state is a spatio-temporal pattern in a network of identical coupled oscillators in which synchronous and asynchronous oscillation coexist. This state of broken symmetry, which usually coexists with a stable spatially symmetric state, has intrigued the nonlinear dynamics community since its discovery in the early 2000s. Recent experiments have led to increasing interest in the origin and dynamics of these states. Here we review the history of research on chimera states and highlight...

  11. Chimera states in systems of nonlocal nonidentical phase-coupled oscillators

    Xie, Jianbo; Kao, Hsien-Ching; Knobloch, Edgar

    2015-01-01

    Chimera states consisting of domains of coherently and incoherently oscillating nonlocally-coupled phase oscillators in systems with spatial inhomogeneity are studied. The inhomogeneity is introduced through the dependence of the oscillator frequency on its location. Two types of spatial inhomogeneity, localized and spatially periodic, are considered and their effects on the existence and properties of multi-cluster and traveling chimera states are explored. The inhomogeneity is found to brea...

  12. Clustering as a prerequisite for chimera states in globally coupled systems

    Schmidt, Lennart; Krischer, Katharina

    2014-01-01

    The coexistence of coherently and incoherently oscillating parts in a system of identical oscillators with symmetrical coupling, i.e., a chimera state, is even observable with uniform global coupling. We address the question of the prerequisites for these states to occur in globally coupled systems. By analyzing two different types of chimera states found for nonlinear global coupling, we show that a clustering mechanism to split the ensemble into two groups is needed as a first step. In fact...

  13. When Nonlocal Coupling Between Oscillators Becomes Stronger: Patched Synchrony or Multi-Chimera States

    Omelchenko, Iryna; Omel'chenko, Oleh E.; Hövel, Philipp; Schöll, Eckehard

    2012-01-01

    Systems of nonlocally coupled oscillators can exhibit complex spatio-temporal patterns, called chimera states, which consist of coexisting domains of spatially coherent (synchronized) and incoherent dynamics. We report on a novel form of these states, found in a widely used model of a limit-cycle oscillator if one goes beyond the limit of weak coupling typical for phase oscillators. Then patches of synchronized dynamics appear within the incoherent domain giving rise to a multi-chimera state....

  14. Cascades of Multi-headed Chimera States for Coupled Phase Oscillators

    Maistrenko, Yuri L.; Vasylenko, Anna; Sudakov, Oleksandr; Levchenko, Roman; Maistrenko, Volodymyr L.

    2014-01-01

    Chimera state is a recently discovered dynamical phenomenon in arrays of nonlocally coupled oscillators, that displays a self-organized spatial pattern of co-existing coherence and incoherence. We discuss the appearance of the chimera states in networks of phase oscillators with attractive and with repulsive interactions, i.e. when the coupling respectively favors synchronization or works against it. By systematically analyzing the dependence of the spatiotemporal dynamics on the level of cou...

  15. TCP: a tool for designing chimera proteins based on the tertiary structure information

    Nishida Reina; Yoneya Takashi

    2009-01-01

    Abstract Background Chimera proteins are widely used for the analysis of the protein-protein interaction region. One of the major issues is the epitope analysis of the monoclonal antibody. In the analysis, a continuous portion of an antigen is sequentially substituted into a different sequence. This method works well for an antibody recognizing a linear epitope, but not for that recognizing a discontinuous epitope. Although the designing the chimera proteins based on the tertiary structure in...

  16. Characteristic distribution of finite-time Lyapunov exponents for chimera states

    André E. Botha

    2016-01-01

    Our fascination with chimera states stems partially from the somewhat paradoxical, yet fundamental trait of identical, and identically coupled, oscillators to split into spatially separated, coherently and incoherently oscillating groups. While the list of systems for which various types of chimeras have already been detected continues to grow, there is a corresponding increase in the number of mathematical analyses aimed at elucidating the fundamental reasons for this surprising behaviour. B...

  17. Application of a Chimera Full Potential Algorithm for Solving Aerodynamic Problems

    Holst, Terry L.; Kwak, Dochan (Technical Monitor)

    1997-01-01

    A numerical scheme utilizing a chimera zonal grid approach for solving the three dimensional full potential equation is described. Special emphasis is placed on describing the spatial differencing algorithm around the chimera interface. Results from two spatial discretization variations are presented; one using a hybrid first-order/second-order-accurate scheme and the second using a fully second-order-accurate scheme. The presentation is highlighted with a number of transonic wing flow field computations.

  18. Observation and characterization of chimera states in coupled dynamical systems with nonlocal coupling

    Gopal, R; Chandrasekar, V. K.; Venkatesan, A.; Lakshmanan, M.

    2014-01-01

    By developing the concepts of strength of incoherence and discontinuity measure, we show that a distinct quantitative characterization of chimera and multichimera states which occur in networks of coupled nonlinear dynamical systems admitting nonlocal interactions of finite radius can be made. These measures also clearly distinguish between chimera or multichimera states (both stable and breathing types) and coherent and incoherent as well as cluster states....

  19. Chimera-like states in an ensemble of globally coupled oscillators

    Yeldesbay, Azamat; Pikovsky, Arkady; Rosenblum, Michael

    2014-01-01

    We demonstrate emergence of a complex state in a homogeneous ensemble of globally coupled identical oscillators, reminiscent of chimera states in locally coupled oscillator lattices. In this regime some part of the ensemble forms a regularly evolving cluster, while all other units irregularly oscillate and remain asynchronous. We argue that chimera emerges because of effective bistability which dynamically appears in the originally monostable system due to internal delayed feedback in individ...

  20. Greengenes: Chimera-checked 16S rRNA gene database and workbenchcompatible in ARB

    DeSantis, T.Z.; Hugenholtz, P.; Larsen, N.; Rojas, M.; Brodie,E.L; Keller, K.; Huber, T.; Dalevi, D.; Hu, P.; Andersen, G.L.

    2006-02-01

    A 16S rRNA gene database (http://greengenes.lbl.gov) addresses limitations of public repositories by providing chimera-screening, standard alignments and taxonomic classification using multiple published taxonomies. It was revealed that incongruent taxonomic nomenclature exists among curators even at the phylum-level. Putative chimeras were identified in 3% of environmental sequences and 0.2% of records derived from isolates. Environmental sequences were classified into 100 phylum-level lineages within the Archaea and Bacteria.

  1. Effect of glycyrrhizin on pseudomonal skin infections in human-mouse chimeras.

    Yoshida, Shohei; Lee, Jong O; Nakamura, Kiwamu; Suzuki, Sumihiro; Hendon, David N; Kobayashi, Makiko; Suzuki, Fujio

    2014-01-01

    In our previous studies, peripheral blood lineage(-)CD34(+)CD31(+) cells (CD31(+) IMC) appearing in severely burned patients have been characterized as inhibitor cells for the production of β-defensins (HBDs) by human epidermal keratinocytes (NHEK). In this study, the effect of glycyrrhizin on pseudomonal skin infections was studied in a chimera model of thermal injury. Two different chimera models were utilized. Patient chimeras were created in murine antimicrobial peptide-depleted NOD-SCID IL-2rγ(null) mice that were grafted with unburned skin tissues of severely burned patients and inoculated with the same patient peripheral blood CD31(+) IMC. Patient chimera substitutes were created in the same mice that were grafted with NHEK and inoculated with experimentally induced CD31(+) IMC. In the results, both groups of chimeras treated with glycyrrhizin resisted a 20 LD50 dose of P. aeruginosa skin infection, while all chimeras in both groups treated with saline died within 3 days of the infection. Human antimicrobial peptides were detected from the grafted site tissues of both groups of chimeras treated with glycyrrhizin, while the peptides were not detected in the same area tissues of controls. HBD-1 was produced by keratinocytes in transwell-cultures performed with CD31(+) IMC and glycyrrhizin. Also, inhibitors (IL-10 and CCL2) of HBD-1 production by keratinocytes were not detected in cultures of patient CD31(+) IMC treated with glycyrrhizin. These results indicate that sepsis stemming from pseudomonal grafted site infections in a chimera model of burn injury is controllable by glycyrrhizin. Impaired antimicrobial peptide production at the infection site of severely burned patients may be restored after treatment with glycyrrhizin. PMID:24497916

  2. Effect of glycyrrhizin on pseudomonal skin infections in human-mouse chimeras.

    Shohei Yoshida

    Full Text Available In our previous studies, peripheral blood lineage(-CD34(+CD31(+ cells (CD31(+ IMC appearing in severely burned patients have been characterized as inhibitor cells for the production of β-defensins (HBDs by human epidermal keratinocytes (NHEK. In this study, the effect of glycyrrhizin on pseudomonal skin infections was studied in a chimera model of thermal injury. Two different chimera models were utilized. Patient chimeras were created in murine antimicrobial peptide-depleted NOD-SCID IL-2rγ(null mice that were grafted with unburned skin tissues of severely burned patients and inoculated with the same patient peripheral blood CD31(+ IMC. Patient chimera substitutes were created in the same mice that were grafted with NHEK and inoculated with experimentally induced CD31(+ IMC. In the results, both groups of chimeras treated with glycyrrhizin resisted a 20 LD50 dose of P. aeruginosa skin infection, while all chimeras in both groups treated with saline died within 3 days of the infection. Human antimicrobial peptides were detected from the grafted site tissues of both groups of chimeras treated with glycyrrhizin, while the peptides were not detected in the same area tissues of controls. HBD-1 was produced by keratinocytes in transwell-cultures performed with CD31(+ IMC and glycyrrhizin. Also, inhibitors (IL-10 and CCL2 of HBD-1 production by keratinocytes were not detected in cultures of patient CD31(+ IMC treated with glycyrrhizin. These results indicate that sepsis stemming from pseudomonal grafted site infections in a chimera model of burn injury is controllable by glycyrrhizin. Impaired antimicrobial peptide production at the infection site of severely burned patients may be restored after treatment with glycyrrhizin.

  3. Cell surface appearance of unexpected host MHC determinants on thymocytes from radiation bone marrow chimeras

    The phenotypic appearance of cell surface antigens on murine thymocytes from long-term radiation bone marrow chimeras was analyzed using indirect immunofluorescence and flow microfluorometry. Cells maturing in the thymi of these mice were typed for MHC (Kk, I-Ak, H-2b, Kb, and Ib) and non-MHC (Lty 1, Ly 9, and TL) determinants. All cells were of donor origin as determined by non-MHC (Ly) phenotype in P1 leads to P2, P1 x P2 leads to P1, and P1 leads to P2 radiation chimeras. In contrast, the MHC phenotypes of these thymocytes were markedly affected by the host environment. Specifically, H-2 and I-A determinants of both parental phenotypes were detected on thymocytes from P1 leads to P1 x P2 chimeras; I-A determinants of host phenotype were present, whereas I-A determinants of donor phenotype were reduced on thymocytes from P1 x P2 leads to P1 chimeras; and thymocytes from P1 leads to P2 chimeras possessed H-2 and I-A determinants of host phenotype but showed reduction of donor I-A phenotype determinants. The appearance of host cell surface H-2 and I-A determinants on thymocytes from chimeras closely parallels the functional recognition of MHC determinants by T cells from chimeric mice and thus may be significantly related to the development of the self-recognition repertoire by maturing T cells

  4. The DEAD-Box Protein DP103 (Ddx20 or Gemin-3) Represses Orphan Nuclear Receptor Activity via SUMO Modification

    Lee, Martin B.; Lebedeva, Lioudmila A.; Suzawa, Miyuki; Wadekar, Subhagya A.; Desclozeaux, Marion; Ingraham, Holly A.

    2005-01-01

    Structural analysis of nuclear receptor subfamily V orphan nuclear receptors suggests that ligand-independent mechanisms must regulate this subclass of receptors. Here, we report that steroidogenic factor 1 (SF-1) and liver receptor homolog 1 are repressed via posttranslational SUMO modification at conserved lysines within the hinge domain. Indeed, mutating these lysines or adding the SUMO isopeptidase SENP1 dramatically increased both native and Gal4-chimera receptor activities. The mechanis...

  5. Molecular determinants of desensitization and assembly of the chimeric GABA(A) receptor subunits (alpha1/gamma2) and (gamma2/alpha1) in combinations with beta2 and gamma2

    Elster, L; Kristiansen, U; Pickering, D S;

    2001-01-01

    Two gamma-aminobutyric acid(A) (GABA(A)) receptor chimeras were designed in order to elucidate the structural requirements for GABA(A) receptor desensitization and assembly. The (alpha1/gamma2) and (gamma2/alpha1) chimeric subunits representing the extracellular N-terminal domain of alpha1 or gamma...... opposed to the staining of the (gamma2/alpha1)-containing receptors, which was only slightly higher than background. To explain this, the (alpha1/gamma2) and (gamma2/alpha1) chimeras may act like alpha1 and gamma2 subunits, respectively, indicating that the extracellular N-terminal segment is important...... for assembly. However, the (alpha1/gamma2) chimeric subunit had characteristics different from the alpha1 subunit, since the (alpha1/gamma2) chimera gave rise to no desensitization after GABA stimulation in whole-cell patch-clamp recordings, which was independent of whether the chimera was expressed...

  6. Chronic Exposure to Androgenic-Anabolic Steroids Exacerbates Axonal Injury and Microgliosis in the CHIMERA Mouse Model of Repetitive Concussion.

    Namjoshi, Dhananjay R; Cheng, Wai Hang; Carr, Michael; Martens, Kris M; Zareyan, Shahab; Wilkinson, Anna; McInnes, Kurt A; Cripton, Peter A; Wellington, Cheryl L

    2016-01-01

    Concussion is a serious health concern. Concussion in athletes is of particular interest with respect to the relationship of concussion exposure to risk of chronic traumatic encephalopathy (CTE), a neurodegenerative condition associated with altered cognitive and psychiatric functions and profound tauopathy. However, much remains to be learned about factors other than cumulative exposure that could influence concussion pathogenesis. Approximately 20% of CTE cases report a history of substance use including androgenic-anabolic steroids (AAS). How acute, chronic, or historical AAS use may affect the vulnerability of the brain to concussion is unknown. We therefore tested whether antecedent AAS exposure in young, male C57Bl/6 mice affects acute behavioral and neuropathological responses to mild traumatic brain injury (TBI) induced with the CHIMERA (Closed Head Impact Model of Engineered Rotational Acceleration) platform. Male C57Bl/6 mice received either vehicle or a cocktail of three AAS (testosterone, nandrolone and 17α-methyltestosterone) from 8-16 weeks of age. At the end of the 7th week of treatment, mice underwent two closed-head TBI or sham procedures spaced 24 h apart using CHIMERA. Post-repetitive TBI (rTBI) behavior was assessed for 7 d followed by tissue collection. AAS treatment induced the expected physiological changes including increased body weight, testicular atrophy, aggression and downregulation of brain 5-HT1B receptor expression. rTBI induced behavioral deficits, widespread axonal injury and white matter microgliosis. While AAS treatment did not worsen post-rTBI behavioral changes, AAS-treated mice exhibited significantly exacerbated axonal injury and microgliosis, indicating that AAS exposure can alter neuronal and innate immune responses to concussive TBI. PMID:26784694

  7. Four-cluster chimera state in non-locally coupled phase oscillator systems with an external potential

    Dynamics of a one-dimensional array of non-locally coupled Kuramoto phase oscillators with an external potential is studied. A four-cluster chimera state is observed for the moderate strength of the external potential. Different from the clustered chimera states studied before, the instantaneous frequencies of the oscillators in a synchronized cluster are different in the presence of the external potential. As the strength of the external potential increases, a bifurcation from the two-cluster chimera state to the four-cluster chimera states can be found. These phenomena are well predicted analytically with the help of the Ott—Antonsen ansatz. (general)

  8. Immune competence of splenic lymphocytes following graft-vs-host disease in mouse allogeneic radiation chimeras

    The abnormal immune response of long-term mouse allogeneic chimeras is reflected by qualitative deficiencies in either T or B lymphocytes. The present study was undertaken to determine if a relationship existed between the severity of graft-vs-host disease (GVHD) that these animals had experienced and a functional defect in either the T or B cell population. The in vitro PFC response of chimera spleen cells to sheep red blood cells (SRBC) was evaluated in the presence of normal T or B lymphocytes 4 to 8 months after marrow transplantation and well beyond the GVHD period. In an analysis of several different allogeneic radiation chimeras, our results showed no relationship between the severity of GVHD experienced and the immunologic capacity of either T or B cells. Thus, different chimera combinations showing similar degrees of GVHD were functionally deficient in one or the other of these two cells types or both with no apparent predilection for abnormality in either population. In examining the quantitative in vitro PFC response to sheep RBC by spleen cells from individual chimeras, we found that the number of PFC formed was related to the severity of GVHD experienced by that animal. A general relationship between severity of GVHD and PFC capacity may also exist between chimeras of different genetic combinations. However, this relationship is not precise since gross exceptions occur. Our results, although documenting further the qualitative abnormalities in T and/or B lymphocytes of radiation chimeras, do not reveal the factor or mechanisms by which these cells are made unresponsive. It is suggested that the tolerance-inducing mechanism of these animals, whether it be humoral blocking factors or suppressor cells, is in some way interfering with the collaboration of T and B cells for antibody production

  9. Human-animal chimeras for vaccine development: an endangered species or opportunity for the developing world?

    Daar Abdallah S

    2010-05-01

    Full Text Available Abstract Background In recent years, the field of vaccines for diseases such as Human Immunodeficiency Virus (HIV which take a heavy toll in developing countries has faced major failures. This has led to a call for more basic science research, and development as well as evaluation of new vaccine candidates. Human-animal chimeras, developed with a 'humanized' immune system could be useful to study infectious diseases, including many neglected diseases. These would also serve as an important tool for the efficient testing of new vaccine candidates to streamline promising candidates for further trials in humans. However, developing human-animal chimeras has proved to be controversial. Discussion Development of human-animal chimeras for vaccine development has been slowed down because of opposition by some philosophers, ethicists and policy makers in the west-they question the moral status of such animals, and also express discomfort about transgression of species barriers. Such opposition often uses a contemporary western world view as a reference point. Human-animal chimeras are often being created for diseases which cause significantly higher morbidity and mortality in the developing world as compared to the developed world. We argue in our commentary that given this high disease burden, we should look at socio-cultural perspectives on human-animal chimera like beings in the developing world. On examination, it's clear that such beings have been part of mythology and cultural descriptions in many countries in the developing world. Summary To ensure that important research on diseases afflicting millions like malaria, HIV, Hepatitis-C and dengue continues to progress, we recommend supporting human-animal chimera research for vaccine development in developing countries (especially China and India which have growing technical expertise in the area. The negative perceptions in some parts of the west about human-animal chimeras can be used as an

  10. Black Box Chimera Check (B2C2): a Windows-Based Software for Batch Depletion of Chimeras from Bacterial 16S rRNA Gene Datasets.

    Gontcharova, Viktoria; Youn, Eunseog; Wolcott, Randall D; Hollister, Emily B; Gentry, Terry J; Dowd, Scot E

    2010-01-01

    The existing chimera detection programs are not specifically designed for "next generation" sequence data. Technologies like Roche 454 FLX and Titanium have been adapted over the past years especially with the introduction of bacterial tag-encoded FLX/Titanium amplicon pyrosequencing methodologies to produce over one million 250-600 bp 16S rRNA gene reads that need to be depleted of chimeras prior to downstream analysis. Meeting the needs of basic scientists who are venturing into high-throughput microbial diversity studies such as those based upon pyrosequencing and specifically providing a solution for Windows users, the B2C2 software is designed to be able to accept files containing large multi-FASTA formatted sequences and screen for possible chimeras in a high throughput fashion. The graphical user interface (GUI) is also able to batch process multiple files. When compared to popular chimera screening software the B2C2 performed as well or better while dramatically decreasing the amount of time required generating and screening results. Even average computer users are able to interact with the Windows .Net GUI-based application and define the stringency to which the analysis should be done. B2C2 may be downloaded from http://www.researchandtesting.com/B2C2. PMID:21339894

  11. T lymphocytes from irradiation chimeras repopulated with 13-day fetal liver cells recognize antigens only in association with self-MHC products

    Nisbet-Brown, E.; Diener, E. (Univ. of Alberta, Edmonton (Canada))

    1986-01-01

    The restriction specificities of maturing thymocytes are determined by the Class II MHC antigens expressed by non-lymphoid thymic tissues. The proliferative response of mature T lymphocytes to antigen-presenting cells (APC) and antigen requires that the APC express the same MHC antigens as the thymus in which the T cells differentiated. Thus, in the two-way bone marrow chimera (A + B----(A x B)F1), T lymphocyte populations of A and B haplotypes have each acquired the potential to recognize antigens associated with either parental haplotype. In spite of the large body of work on MHC restriction, we still do not have a clear understanding of the mechanisms which impose self restriction. The chimeric model systems used previously to study MHC restriction have used adult bone marrow cells as the source of lymphoid precursors. During normal ontogeny, T cells are derived from precursors in the fetal liver and we felt that a direct comparison of T cells from fetal liver and bone marrow-repopulated animals would shed light on the development of MHC restriction specificities during T cell ontogeny in the thymus or prethymically. We found that parental T lymphocyte populations isolated from two-way fetal liver chimeras cooperated only with syngeneic APC, while those from bone marrow chimeras cooperated with APC of either parental haplotype. This suggests that fetal liver and bone marrow may not be equivalent sources of stem cells. Our results may be due to fundamental differences between thymocyte precursors in fetal liver and bone marrow, including the time course of their expression of T cell receptor gene products.

  12. T lymphocytes from irradiation chimeras repopulated with 13-day fetal liver cells recognize antigens only in association with self-MHC products

    The restriction specificities of maturing thymocytes are determined by the Class II MHC antigens expressed by non-lymphoid thymic tissues. The proliferative response of mature T lymphocytes to antigen-presenting cells (APC) and antigen requires that the APC express the same MHC antigens as the thymus in which the T cells differentiated. Thus, in the two-way bone marrow chimera [A + B----(A x B)F1], T lymphocyte populations of A and B haplotypes have each acquired the potential to recognize antigens associated with either parental haplotype. In spite of the large body of work on MHC restriction, we still do not have a clear understanding of the mechanisms which impose self restriction. The chimeric model systems used previously to study MHC restriction have used adult bone marrow cells as the source of lymphoid precursors. During normal ontogeny, T cells are derived from precursors in the fetal liver and we felt that a direct comparison of T cells from fetal liver and bone marrow-repopulated animals would shed light on the development of MHC restriction specificities during T cell ontogeny in the thymus or prethymically. We found that parental T lymphocyte populations isolated from two-way fetal liver chimeras cooperated only with syngeneic APC, while those from bone marrow chimeras cooperated with APC of either parental haplotype. This suggests that fetal liver and bone marrow may not be equivalent sources of stem cells. Our results may be due to fundamental differences between thymocyte precursors in fetal liver and bone marrow, including the time course of their expression of T cell receptor gene products

  13. Title: Chimeras in small, globally coupled networks: Experiments and stability analysis

    Hart, Joseph D.; Bansal, Kanika; Murphy, Thomas E.; Roy, Rajarshi

    Since the initial observation of chimera states, there has been much discussion of the conditions under which these states emerge. The emphasis thus far has mainly been to analyze large networks of coupled oscillators; however, recent studies have begun to focus on the opposite limit: what is the smallest system of coupled oscillators in which chimeras can exist? We experimentally observe chimeras and other partially synchronous patterns in a network of four globally-coupled chaotic opto-electronic oscillators. By examining the equations of motion, we demonstrate that symmetries in the network topology allow a variety of synchronous states to exist, including cluster synchronous states and a chimera state. Using the group theoretical approach recently developed for analyzing cluster synchronization, we show how to derive the variational equations for these synchronous patterns and calculate their linear stability. The stability analysis gives good agreement with our experimental results. Both experiments and simulations suggest that these chimera states often appear in regions of multistability between global, cluster, and desynchronized states.

  14. Function of nonstructural 5A protein of genotype 2a in replication and infection of HCV with gene substitution

    Yong-Zhi Wang; Wen-Bo Wang; Ming-Mei Cao; Wen Wang; Lan-Juan Zhao; Gang Xu; Hao Ren; Zhong-Tian Qi

    2011-01-01

    AIM: To explore the function of Nonstructural 5A (NS5A) protein of genotype 2a (JFH1) in the replication and infection of hepatitis C virus (HCV).METHODS: Intergenotypic chimera FL-J6JFH/J4NS5A was constructed by inserting NS5A gene from 1b stain HC-J4 by the overlapping polymerase chain reaction (PPCR) method and the restriction enzyme reaction.In vitro RNA transcripts of chimera, prototype J6JFH and negative control J6JFH1 (GNDD) were prepared and transfected into Huh-7.5 cells with liposomes. Immunofluorescence assay (IFA), fluorescence quantitative PCR and infection assay were performed to determine the protein expression and gene replication in Huh-7.5 cells.RESULTS: The HCV RNA levels in FL-J6JFH/J4NS5A chimera RNA transfected cells were significantly lower than the wild type at any indicated time point (2.58± 5.97×106 vs 4.27 ± 1.72×104, PP = 00.0032). The maximal level of HCV RNA in chimera was 5.6±1.8×104 GE/μg RNA at day 34 after transfection, while the wild type reached a peak level at day 13 which was 126 folds higher (70.65 ± 14.11×105 vs 0.56 ± 0.90×105, = 0.028). HCV proteins could also be detected by IFA in chimera-transfected cells with an obviously low level. Infection assay showed that FL-J6JFH/J4NS5A chimera could produce infectious virus particles, ranging from 10 ± 5 ffu/mL to 78.3 ± 23.6 ffu/mL, while that of FL-J6JFH1 ranged from 5.8 ± 1.5×102 ffu/mL to 2.5 ± 1.4×104 ffu/mL.CONCLUSION: JFH1 NS5A might play an important role in the robust replication of J6JFH1. The establishment of FL-J6JFH/J4NS5A provided a useful platform for studying the function of other proteins of HCV.

  15. Allogeneic unresponsiveness to orthotopic cardiac transplants in DL-A-identical radiation chimeras

    Nine Cooperstown beagles of known DL-A genotypes were exposed to supralethal total-body irradiation and received bone-marrow allografts from DL-A-identical donors. Four to 5 months later, the resulting chimeras received orthotopic cardiac allografts from their corresponding donors of marrow. Six chimeras died of operative complications in the immediate postoperative period. The other 3 chimeras survived from 173 to 547 days; 1 dog died at 173 days as a result of right-sided heart failure, secondary to stenosis at the site of the pulmonary artery anastomosis. The other two recipients continue to be active and healthy at 545 and 547 days. The results indicate that dogs can be rendered specifically tolerant to orthotopic cardiac allografts by supralethal total-body irradiation and the transplantation of marrow obtained from the prospective allograft donor

  16. A Multitier System for the Verification, Visualization and Management of CHIMERA

    CHIMERA is a multi-dimensional radiation hydrodynamics code designed to study core-collapse supernovae. The code is made up of three essentially independent parts: a hydrodynamics module, a nuclear burning module, and a neutrino transport solver combined within an operator-split approach. Given CHIMERA's complexity and pace of ongoing development, a new support system, Bellerophon, has been designed and implemented to perform automated verification, visualization and management tasks while integrating with other workflow systems utilized by CHIMERA's development group. In order to achieve these goals, a multitier approach has been adopted. By integrating supercomputing platforms, visualization clusters, a dedicated web server and a client-side desktop application, this system attempts to provide an encapsulated, end-to-end solution to these needs.

  17. Chimera and phase-cluster states in populations of coupled chemical oscillators

    Tinsley, Mark R.; Nkomo, Simbarashe; Showalter, Kenneth

    2012-09-01

    Populations of coupled oscillators may exhibit two coexisting subpopulations, one with synchronized oscillations and the other with unsynchronized oscillations, even though all of the oscillators are coupled to each other in an equivalent manner. This phenomenon, discovered about ten years ago in theoretical studies, was then further characterized and named the chimera state after the Greek mythological creature made up of different animals. The highly counterintuitive coexistence of coherent and incoherent oscillations in populations of identical oscillators, each with an equivalent coupling structure, inspired great interest and a flurry of theoretical activity. Here we report on experimental studies of chimera states and their relation to other synchronization states in populations of coupled chemical oscillators. Our experiments with coupled Belousov-Zhabotinsky oscillators and corresponding simulations reveal chimera behaviour that differs significantly from the behaviour found in theoretical studies of phase-oscillator models.

  18. The Chimera II Real-Time Operating System for advanced sensor-based control applications

    Stewart, David B.; Schmitz, Donald E.; Khosla, Pradeep K.

    1992-01-01

    Attention is given to the Chimera II Real-Time Operating System, which has been developed for advanced sensor-based control applications. The Chimera II provides a high-performance real-time kernel and a variety of IPC features. The hardware platform required to run Chimera II consists of commercially available hardware, and allows custom hardware to be easily integrated. The design allows it to be used with almost any type of VMEbus-based processors and devices. It allows radially differing hardware to be programmed using a common system, thus providing a first and necessary step towards the standardization of reconfigurable systems that results in a reduction of development time and cost.

  19. Distinct fates of self-specific T cells developing in irradiation bone marrow chimeras: Clonal deletion, clonal anergy, or in vitro responsiveness to self-Mls-1a controlled by hemopoietic cells in the thymus

    Speiser, D.E.; Chvatchko, Y.; Zinkernagel, R.M.; MacDonald, H.R. (Ludwig Institute for Cancer Research, Epalinges (Switzerland))

    1990-11-01

    Elimination of potentially self-reactive T lymphocytes during their maturation in the thymus has been shown to be a major mechanism in accomplishing self-tolerance. Previous reports demonstrated that clonal deletion of self-Mls-1a-specific V beta 6+ T lymphocyte is controlled by a radiosensitive I-E+ thymic component. Irradiation chimeras reconstituted with I-E- bone marrow showed substantial numbers of mature V beta 6+ T cells despite host Mls-1a expression. Analysis of the functional properties of such chimeric T cells revealed a surprising variability in their in vitro reactivity to host Mls-1a, depending on the H-2 haplotype of stem cells used for reconstitution. In chimeras reconstituted with B10.S (H-2s) stem cells, mature V beta 6+ lymphocytes were present but functionally anergic to host-type Mls-1a in vitro. In contrast, in chimeras reconstituted with B10.G (H-2q) bone marrow, nondeleted V beta 6+ cells were highly responsive to Mls-1a in vitro. These findings suggest that clonal anergy of V beta 6+ cells to self-Mls-1a may be controlled by the affinity/avidity of T cell receptor interactions with bone marrow-derived cells in the thymus depending on the major histocompatibility complex class II molecules involved. Furthermore, chimeras bearing host (Mls-1a)-reactive V beta 6+ cells did not differ clinically from those with anergic or deleted V beta 6+ cells and survived more than one year without signs of autoimmune disease. Interestingly, their spleen cells had no Mls-1a stimulatory capacity in vitro. Therefore, regulation at the level of antigen presentation may be an alternative mechanism for maintenance of tolerance to certain self-antigens such as Mls-1a.

  20. Distinct fates of self-specific T cells developing in irradiation bone marrow chimeras: Clonal deletion, clonal anergy, or in vitro responsiveness to self-Mls-1a controlled by hemopoietic cells in the thymus

    Elimination of potentially self-reactive T lymphocytes during their maturation in the thymus has been shown to be a major mechanism in accomplishing self-tolerance. Previous reports demonstrated that clonal deletion of self-Mls-1a-specific V beta 6+ T lymphocyte is controlled by a radiosensitive I-E+ thymic component. Irradiation chimeras reconstituted with I-E- bone marrow showed substantial numbers of mature V beta 6+ T cells despite host Mls-1a expression. Analysis of the functional properties of such chimeric T cells revealed a surprising variability in their in vitro reactivity to host Mls-1a, depending on the H-2 haplotype of stem cells used for reconstitution. In chimeras reconstituted with B10.S (H-2s) stem cells, mature V beta 6+ lymphocytes were present but functionally anergic to host-type Mls-1a in vitro. In contrast, in chimeras reconstituted with B10.G (H-2q) bone marrow, nondeleted V beta 6+ cells were highly responsive to Mls-1a in vitro. These findings suggest that clonal anergy of V beta 6+ cells to self-Mls-1a may be controlled by the affinity/avidity of T cell receptor interactions with bone marrow-derived cells in the thymus depending on the major histocompatibility complex class II molecules involved. Furthermore, chimeras bearing host (Mls-1a)-reactive V beta 6+ cells did not differ clinically from those with anergic or deleted V beta 6+ cells and survived more than one year without signs of autoimmune disease. Interestingly, their spleen cells had no Mls-1a stimulatory capacity in vitro. Therefore, regulation at the level of antigen presentation may be an alternative mechanism for maintenance of tolerance to certain self-antigens such as Mls-1a

  1. Chimera states in a population of identical oscillators under planar cross-coupling

    C R Hens; A Mishra; P K Roy; A Sen; S K Dana

    2015-02-01

    We report the existence of chimera states in an assembly of identical nonlinear oscillators that are globally linked to each other in a simple planar cross-coupled form. The rotational symmetry breaking of the coupling term appears to be responsible for the emergence of these collective states that display a characteristic coexistence of coherent and incoherent behaviour. The finding, observed in both a collection of van der Pol oscillators and chaotic Rössler oscillators, further simplifies the existence criterion for chimeras, thereby broadens the range of their applicability to real-world situations.

  2. Marginal chimera state at cross-frequency locking of pulse-coupled neural networks

    Bolotov, M. I.; Osipov, G. V.; Pikovsky, A.

    2016-03-01

    We consider two coupled populations of leaky integrate-and-fire neurons. Depending on the coupling strength, mean fields generated by these populations can have incommensurate frequencies or become frequency locked. In the observed 2:1 locking state of the mean fields, individual neurons in one population are asynchronous with the mean fields, while in another population they have the same frequency as the mean field. These synchronous neurons form a chimera state, where part of them build a fully synchronized cluster, while other remain scattered. We explain this chimera as a marginal one, caused by a self-organized neutral dynamics of the effective circle map.

  3. In vitro induction of mutation and separation of chimeras in Gerbera jamesonii

    Using ex vitro leaves as objects to be irradiated and to induce variation in sixteen Gerbera jamesonii cultivars, reproduced from adventitious buds, resulted in obtaining the mutants which inflorescence color was uniformly changed and which newly acquired traits recurred in the second generation of plants reproduced vegetatively from the isolated shoot tips. However, chimeras appeared among the vM1 plants exposed to various doses of gamma rays (5-25 Gy and they constituted almost half of the mutated plants. A further propagation of chimeras from leaf explants forming adventitious shoots significantly increased the number of solid mutants with uniformly changed inflorescence color in the vM1 generation. (author)

  4. Induction of chlorophyll chimeras and chlorophyll mutations in mungbean (Vigna radiata) cv. T44

    Uniform and healthy seeds of mungbean (Vigna radiata) cv. T44 were exposed to varying doses of gamma rays, ethyl methane sulphonate (EMS) and combination treatment of gamma rays with EMS. The data were recorded for seed germination, plant survival, frequency and spectrum of chlorophyll chimeras in M1 and chlorophyll mutations in M2 generation. Among all, the combination treatments were found most effective for inducing chlorophyll chimeras and chlorophyll mutations than the gamma rays or EMS alone. Of the mutants under reference, the albino, xantha and chlorina showed monogenic recessive while viridis exhibited digenic recessive inheritance. (author). 8 refs., 2 tabs

  5. Hemopoietic precursor-cells in radiation chimeras restored by bone marrow of adult thymectomized mice

    Radioprotective capacity of bone marrow CFUs of adult thymectomized mice was studied. Lethaly irradiated mice were inoculated with bone marrow of mice thymectomized 8-11 months before. The colony forming capacity and proliferative rate of CFUs were studied 1-7.5 months after obtaining the radiation chimeras. It has been shown that proliferative capacity of bone marrow of adult thymectomized mice was reduced in comparison with that of normal animals. We also found that the content of CFUs in bone of those chimeras was reduced later - after 7.5 months. In this period (1-7.5 months) the cellularity of bone marrow did not change

  6. Application of Chimera Grid Scheme to Combustor Flowfields at all Speeds

    Yungster, Shaye; Chen, Kuo-Huey

    1997-01-01

    A CFD method for solving combustor flowfields at all speeds on complex configurations is presented. The approach is based on the ALLSPD-3D code which uses the compressible formulation of the flow equations including real gas effects, nonequilibrium chemistry and spray combustion. To facilitate the analysis of complex geometries, the chimera grid method is utilized. To the best of our knowledge, this is the first application of the chimera scheme to reacting flows. In order to evaluate the effectiveness of this numerical approach, several benchmark calculations of subsonic flows are presented. These include steady and unsteady flows, and bluff-body stabilized spray and premixed combustion flames.

  7. A PTAS for the Classical Ising Spin Glass Problem on the Chimera Graph Structure

    Saket, Rishi

    2013-01-01

    We present a polynomial time approximation scheme (PTAS) for the minimum value of the classical Ising Hamiltonian with linear terms on the Chimera graph structure as defined in the recent work of McGeoch and Wang. The result follows from a direct application of the techniques used by Bansal, Bravyi and Terhal who gave a PTAS for the same problem on planar and, in particular, grid graphs. We also show that on Chimera graphs, the trivial lower bound is within a constant factor of the optimum.

  8. SLC45A3-ELK4 Chimera in Prostate Cancer: Spotlight on Cis-Splicing

    Kumar-Sinha, Chandan; Kalyana-Sundaram, Shanker; Chinnaiyan, Arul M.

    2012-01-01

    Using a series of detailed experiments, Zhang et al establish that the prostate cancer RNA chimera SLC45A3-ELK4 is generated by cis-splicing between the two adjacent genes and does not involve DNA rearrangements or trans-splicing. The chimera expression is induced by androgen treatment likely by overcoming the read-through block imposed by the intergenic CCCTC-insulators bound by CTCF repressor protein. The chimeric transcript, but not wild type ELK4, is shown to augment prostate cancer cell ...

  9. Chimera states: coexistence of coherence and incoherence in networks of coupled oscillators

    Panaggio, Mark J.; Abrams, Daniel M.

    2015-03-01

    A chimera state is a spatio-temporal pattern in a network of identical coupled oscillators in which synchronous and asynchronous oscillation coexist. This state of broken symmetry, which usually coexists with a stable spatially symmetric state, has intrigued the nonlinear dynamics community since its discovery in the early 2000s. Recent experiments have led to increasing interest in the origin and dynamics of these states. Here we review the history of research on chimera states and highlight major advances in understanding their behaviour.

  10. Non-invasive screening for Alzheimer's disease by sensing salivary sugar using Drosophila cells expressing gustatory receptor (Gr5a immobilized on an extended gate ion-sensitive field-effect transistor (EG-ISFET biosensor.

    Hui-Chong Lau

    Full Text Available Body fluids are often used as specimens for medical diagnosis. With the advent of advanced analytical techniques in biotechnology, the diagnostic potential of saliva has been the focus of many studies. We recently reported the presence of excess salivary sugars, in patients with Alzheimer's disease (AD. In the present study, we developed a highly sensitive, cell-based biosensor to detect trehalose levels in patient saliva. The developed biosensor relies on the overexpression of sugar sensitive gustatory receptors (Gr5a in Drosophila cells to detect the salivary trehalose. The cell-based biosensor was built on the foundation of an improved extended gate ion-sensitive field-effect transistor (EG-ISFET. Using an EG-ISFET, instead of a traditional ion-sensitive field-effect transistor (ISFET, resulted in an increase in the sensitivity and reliability of detection. The biosensor was designed with the gate terminals segregated from the conventional ISFET device. This design allows the construction of an independent reference and sensing region for simultaneous and accurate measurements of samples from controls and patients respectively. To investigate the efficacy of the cell-based biosensor for AD screening, we collected 20 saliva samples from each of the following groups: participants diagnosed with AD, participants diagnosed with Parkinson's disease (PD, and a control group composed of healthy individuals. We then studied the response generated from the interaction of the salivary trehalose of the saliva samples and the Gr5a in the immobilized cells on an EG-ISFET sensor. The cell-based biosensor significantly distinguished salivary sugar, trehalose of the AD group from the PD and control groups. Based on these findings, we propose that salivary trehalose, might be a potential biomarker for AD and could be detected using our cell-based EG-ISFET biosensor. The cell-based EG-ISFET biosensor provides a sensitive and direct approach for salivary sugar

  11. Different domains of the glucagon and glucagon-like peptide-1 receptors provide the critical determinants of ligand selectivity

    Runge, S; Wulff, B S; Madsen, K;

    2003-01-01

    domain with the GLP-1 receptor core domain (chimera A) completely rescued the affinity and potency of GLP-1(7-20)/glucagon(15-29) without compromising the affinity and potency of glucagon. Substituting transmembrane segment 1 (TM1), TM6, TM7, the third extracellular loop and the intracellular carboxy......-terminus of chimera A with the corresponding glucagon receptor segments re-established the ability to distinguish GLP-1(7-20)/glucagon(15-29) from glucagon. Corroborant results were obtained with the opposite chimeric peptide glucagon(1-14)/GLP-1(21-37). (3) The results suggest that the glucagon and GLP-1...

  12. Antiviral T cell competence and restriction specificity of mixed allogeneic (P1 + P2----P1) irradiation chimeras

    Mixed irradiation bone marrow chimeras were prepared by reconstituting lethally irradiated C57BL/10 (B10) or B10.D2 mice with T cell-depleted bone marrow cells of B10 plus B10.D2 origin. These chimeras were healthy and survived well under conventional housing conditions and after experimental laboratory infections. Of a total of 17 chimeras tested, 2 died spontaneously or from the injected virus. Twelve of fifteen chimeras mounted a measurable cytotoxic T cell response to virus. Despite approximately equal percentages of B10 and B10.D2 lymphocytes in chimeras, cytotoxic T cell responses to vaccinia virus and lymphocytic choriomeningitis virus were mediated variably by either syngeneic or allogeneic donor lymphocytes; thus the H-2 type of effector T cells frequently did not correspond to the 50:50 distribution of spleen or peripheral blood lymphocytes. Cytotoxic responses were restricted exclusively to recipient H-2 type. All mixed chimeras examined were able to mount a good IgG response to vesicular stomatitis virus. These results confirm previous data suggesting that such mixed chimeras are healthy and immunocompetent and demonstrate strict recipient-determined restriction specificity of effector T cells; they also suggest that if T help is necessary for induction of virus-specific cytotoxic T cells, it does not require host-restricted interactions between helper T cells and precursor cytotoxic T cells

  13. Construction of RNA-Quantum Dot Chimera for Nanoscale Resistive Biomemory Application.

    Lee, Taek; Yagati, Ajay Kumar; Pi, Fengmei; Sharma, Ashwani; Choi, Jeong-Woo; Guo, Peixuan

    2015-07-28

    RNA nanotechnology offers advantages to construct thermally and chemically stable nanoparticles with well-defined shape and structure. Here we report the development of an RNA-QD (quantum dot) chimera for resistive biomolecular memory application. Each QD holds two copies of the pRNA three-way junction (pRNA-3WJ) of the bacteriophage phi29 DNA packaging motor. The fixed quantity of two RNAs per QD was achieved by immobilizing the pRNA-3WJ with a Sephadex aptamer for resin binding. Two thiolated pRNA-3WJ serve as two feet of the chimera that stand on the gold plate. The RNA nanostructure served as both an insulator and a mediator to provide defined distance between the QD and gold. Immobilization of the chimera nanoparticle was confirmed with scanning tunneling microscopy. As revealed by scanning tunneling spectroscopy, the conjugated pRNA-3WJ-QD chimera exhibited an excellent electrical bistability signal for biomolecular memory function, demonstrating great potential for the development of resistive biomolecular memory and a nano-bio-inspired electronic device for information processing and computing. PMID:26135474

  14. Application of the Chimera overlapped grid scheme to simulation of Space Shuttle ascent flows

    Buning, Pieter G.; Parks, Steven J.; Chan, William M.; Renze, Kevin J.

    1992-01-01

    Several issues relating to the application of Chimera overlapped grids to complex geometries and flowfields are discussed. These include the addition of geometric components with different grid topologies, gridding for intersecting pieces of geometry, and turbulence modeling in grid overlap regions. Sample results are presented for transonic flow about the Space Shuttle launch vehicle. Comparisons with wind tunnel and flight measured pressures are shown.

  15. Influence of Lymphopoiesis Control Mechanisms on the Recovery of Immune Capacities in Isogenic Radiation Chimeras

    The capacities of cells belonging either to foetal liver or to adult bone marrow or spleen are extremely different as far as the production of immunologically competent cells (ICC) by isogenic chimeras is concerned. The study of thymectomized radiation chimeras by the Simonsen test and the Jern technique shows that it is only the spleen or the lymph nodes which are able to bring ICC to a thymectomized animal; the bone marrow and the foetal liver carry only precursor cells which cannot be transformed into ICC when the recipient lacks its thymus. Furthermore, the functional ICC brought to these animals by the spleen cell suspensions have limited life span, not exceeding 300- 400 days. It must also be stressed that the thymectomized isogenic chimeras treated by bone marrow or foetal liver, although they display no immune reactivity, have an increased production of immunoglobulins. Therefore it seems that in this case there is no regulation of the production, differentiation and maturation of ICC. However, a control of the production and/or reactivity of ICC does exist in non-thymectomized radiation chimeras. This can be shown by the Simonsen test and the Jern technique for the primary reactions and by the study of homologous tumour graft rejection for the second-set reaction. This regulatory activity could be mediated either through a feed-back mechanism acting on ICC production or through a more complex process involving an interaction between antigens and cells. (author)

  16. Thoughts on the chimera method of simulation of three-dimensional viscous flow

    Steger, Joseph L.

    1991-01-01

    The chimera overset grid is reviewed and discussed relative to other procedures for simulating flow about complex configurations. It is argued that while more refinement of the technique is needed, current schemes are competitive to unstructured grid schemes and should ultimately prove more useful.

  17. The Chimera Method of Simulation for Unsteady Three-Dimensional Viscous Flow

    Meakin, Robert L.

    1996-01-01

    The Chimera overset grid method is reviewed and discussed in the context of a method of solution and analysis of unsteady three-dimensional viscous flows. The state of maturity of the various pieces of support software required to use the approach is discussed. A variety of recent applications of the method is presented. Current limitations of the approach are defined.

  18. Studies on the mechanism of the self restriction of T cell responses in radiation chimeras

    Recent experiments with murine radiation chimeras have shown that F1 T cells that mature in an H-2 homozygous thymus, as is the case in [F1 → Parent 1] chimeras, are restricted to recognizing foreign antigen in the context of Parent 1 H-2 antigens. Conflicting results on the stringency of self H-2 restriction of T cells from normal mice have suggested that the thymic restriction in chimeras may be due to active suppression of parent 2-restricted T cell clones. We have therefore conducted 3 sets of experiments to test for suppression of maturing T cells that could mediate thymic tutoring of H-2-restriction specificity in chimeras. In 2 sets of experiments, we found no evidence that suppressor cells could be exported from 1 thymus and act either intrathymically on thymocytes in a 2nd thymus or extrathymically on recent thymic emigrants. We believe current data support a role for the thymus in positive as well as negative selection of maturing thymocytes on the basis of self recognition, in the absence of any suppression. Our results do not support the concept that suppression is responsible for the difference in the degree of self preference in the T cells of chimeric mice relative to cell populations obtained from neonatally tolerant mice or from normal mice after acute negative selection

  19. "American Chimera: The Ever-Present Domination of Whiteness, Patriarchy, and Capitalism…A Parable"

    Montoya, Roberto; Matias, Cheryl E.; Nishi, Naomi W. M.; Sarcedo, Geneva L.

    2016-01-01

    In Greek mythology, the Chimera is a fire-breathing monster with three heads: one of a lion, one of a horned goat, and one of a powerful dragon. Of similar construction is the presence of three structures in US society, whiteness, patriarchy, and capitalism, which are overwhelmingly represented, valued, and espoused when examining areas of…

  20. Bioinspired silicification of silica-binding peptide-silk protein chimeras: comparison of chemically and genetically produced proteins.

    Canabady-Rochelle, Laetitia L S; Belton, David J; Deschaume, Olivier; Currie, Heather A; Kaplan, David L; Perry, Carole C

    2012-03-12

    Novel protein chimeras constituted of "silk" and a silica-binding peptide (KSLSRHDHIHHH) were synthesized by genetic or chemical approaches and their influence on silica-silk based chimera composite formation evaluated. Genetic chimeras were constructed from 6 or 15 repeats of the 32 amino acid consensus sequence of Nephila clavipes spider silk ([SGRGGLGGQG AGAAAAAGGA GQGGYGGLGSQG](n)) to which one silica binding peptide was fused at the N terminus. For the chemical chimera, 28 equiv of the silica binding peptide were chemically coupled to natural Bombyx mori silk after modification of tyrosine groups by diazonium coupling and EDC/NHS activation of all acid groups. After silica formation under mild, biomaterial-compatible conditions, the effect of peptide addition on the properties of the silk and chimeric silk-silica composite materials was explored. The composite biomaterial properties could be related to the extent of silica condensation and to the higher number of silica binding sites in the chemical chimera as compared with the genetically derived variants. In all cases, the structure of the protein/chimera in solution dictated the type of composite structure that formed with the silica deposition process having little effect on the secondary structural composition of the silk-based materials. Similarly to our study of genetic silk based chimeras containing the R5 peptide (SSKKSGSYSGSKGSKRRIL), the role of the chimeras (genetic and chemical) used in the present study resided more in aggregation and scaffolding than in the catalysis of condensation. The variables of peptide identity, silk construct (number of consensus repeats or silk source), and approach to synthesis (genetic or chemical) can be used to "tune" the properties of the composite materials formed and is a general approach that can be used to prepare a range of materials for biomedical and sensor-based applications. PMID:22229696

  1. Assay using embryo aggregation chimeras for the detection of nonlethal changes in X-irradiated mouse preimplantation embryos

    We have developed a short-term in vitro assay for the detection of sublethal effects produced by very low levels of ionizing radiation. The assay utilizes mouse embryo aggregation chimeras consisting of one irradiated embryo paired with an unirradiated embryo whose blastomeres have been labeled with fluorescein isothiocyanate (FITC). X irradiation (from 0.05 to 2 Gy) and chimera construction were performed with four-cell stage embryos, and the chimeras were cultured for 40 h to the morula stage. The morulae were partially dissociated with calcium-free culture medium and viewed under phase contrast and epifluorescence microscopy to obtain total embryo cell number and the cellular contribution of irradiated (unlabeled) and control (FITC labeled) embryos per chimera. In chimeras where neither embryo was irradiated, the ratio of the unlabeled blastomeres to the total number of blastomeres per chimera embryo was 0.50 (17.8 +/- 5.6 cells per unlabeled embryo and 17.4 +/- 5.5 cells per FITC-labeled partner embryo). However, in chimeras formed after the unlabeled embryos were irradiated with as little as 0.05 Gy, the ratio of unlabeled blastomeres to the total number of blastomeres per chimera embryo was 0.43 (P less than 0.01). The apparent decreases in cell proliferation were not observed in irradiated embryos that were merely cocultured with control embryos, regardless of whether the embryos were zona enclosed or zona free. We conclude that very low levels of radiation induce sublethal changes in cleaving embryos that are expressed as a proliferative disadvantage within two cell cycles when irradiated embryos are in direct cell-to-cell contact with unirradiated embryos

  2. Differential identification of ID sequence of DNA in cells of rats, mouse, and rat-mouse radiation chimeras

    It is shown that ID-sequence can be used for identification of donor cells of rat-mouse radiation chimeras. The fact of intensive binding of labelled probe with cytoplasmic cell components of neutrophilic series of differentiation is noted. Trace were observed at that both for rats and radiation chimeras, and some times-for mice. The reasons of observed phenomenon are interesting from the viewpoint of working out techniques and characterizing functional peculiarities of cells of different lines and differentiation stages

  3. Chronic graft-versus-host disease in the rat radiation chimera: I. clinical features, hematology, histology, and immunopathology in long-term chimeras

    The clinical features, pathology, and immunopathology of chronic graft-versus-host disease (GVHD) developing in the long-term rat radiation chimera are described. At 6 to 12 months post-transplant, the previously stable ACI/LEW chimeras developed patchy to diffuse severe hair loss and thickened skin folds, and had microscopic features resembling scleroderma, Sjogren's syndrome, and chronic hepatitis. Skin histology showed dermal inflammation and acanthosis with atrophy of the appendages, with progression to dermal sclerosis. The liver revealed chronic hepatitis with bile duct injury and proliferation and periportal piecemeal necrosis. The tongue had considerable submucosal inflammation, muscular necrosis, and atrophy and arteritis. The serous salivary glands, lacrimal glands, and bronchi had lymphocytic inflammation and injury to duct, acinar, and mucosal columnar epithelium. The thymus had lymphocyte depletion of the medulla with prominent epithelium. The spleen and lymph nodes had poorly developed germinal centers but increased numbers of plasma cells. IgM was observed along the basement membrane and around the basal cells of the skin and tongue and along the basement membrane of the bile ducts. IgM was present also in the arteries of the tongue. Immunoglobulins eluted from the skin, cross-reacted with the bile duct epithelium and usually with both ACI and Lewis skin. Increased titers of speckled antinuclear antibodies were present in the serum of rats with chronic (GVHD). Chronic GVHD in the long-term rat radiation chimera is very similar to human chronic GVHD and is a potentially excellent model for autoimmune disorders including scleroderma, Sjorgren's syndrome, and chronic hepatitis

  4. H-2 restriction of the T cell response to chemically induced tumors: evidence from F1 → parent chimeras

    It has been well established that T cells that react to tumor antigen on virus-induced tumors must share H-2D or H-2K specificities with the tumor. It has been impossible to perform similar studies with chemically induced tumors because each chemically induced tumor expresses a unique tumor antigen that cannot be studied in association with other H-2 types. This study provies evidence that H-2 recognition is also necessary for recognition of chemically induced tumors. We have found that F1 → parent chimeras preferentially recognize chemically induced tumors of parental H-2 type. C3H/HeJ and C57BL/6 mice were lethally irradiated and restored with (C3H x C57BL/6) F1 hybrid bone marrow. The F1 → C3H chimera but not the F1 → C57BL/6 chimera was able to respond to a C3H fibrosarcoma in mixed lymphocyte-tumor cell culture and also to neutralize the tumor in an in vivo tumor neutralization assay. On the other hand, the F1 → C57BL/6 chimera but not the F1 → C3H chimera was able to kill the C57BL/6 lymphoma EL4 in an in vitro cytotoxicity assay. Both chimeras were tolerant to C3H and C57BL/6 alloantigens but could respond normally to Con A and to BALB/c spleen cells in mixed lymphocyte cultures and cytotoxicity assay

  5. Navier-Stokes calculations on multi-element airfoils using a chimera-based solver

    Jasper, Donald W.; Agrawal, Shreekant; Robinson, Brian A.

    1993-01-01

    A study of Navier-Stokes calculations of flows about multielement airfoils using a chimera grid approach is presented. The chimera approach utilizes structured, overlapped grids which allow great flexibility of grid arrangement and simplifies grid generation. Calculations are made for two-, three-, and four-element airfoils, and modeling of the effect of gap distance between elements is demonstrated for a two element case. Solutions are obtained using the thin-layer form of the Reynolds averaged Navier-Stokes equations with turbulence closure provided by the Baldwin-Lomax algebraic model or the Baldwin-Barth one equation model. The Baldwin-Barth turbulence model is shown to provide better agreement with experimental data and to dramatically improve convergence rates for some cases. Recently developed, improved farfield boundary conditions are incorporated into the solver for greater efficiency. Computed results show good comparison with experimental data which include aerodynamic forces, surface pressures, and boundary layer velocity profiles.

  6. The Chimera Scheme: Approximate Waveforms for Extreme-Mass-Ratio Inspirals

    Sopuerta, Carlos F

    2011-01-01

    We introduce the Chimera scheme, a new framework to model the dynamics of generic extreme mass-ratio inspirals (stellar compact objects spiraling into a spinning super-massive black hole) and to produce the gravitational waveforms that describe the gravitational wave emission of these systems. The Chimera scheme combines techniques from black hole perturbation theory and post-Minkowskian theory. The orbital evolution is approximated as a sequence of osculating geodesics that shrink due to the stellar compact object's self-acceleration. Lacking a general prescription for this self-force, we here approximate it locally in time via a post-Minkowskian expansion. The orbital evolution is thus equivalent to evolving the geodesic equations with time-dependent orbital elements, as dictated by this post-Minkowskian radiation-reaction prescription. Gravitational radiation is modeled via a multipolar expansion in post-Minkowskian theory, here taken up to mass hexadecapole and current octopole order. To complete the sche...

  7. Enhanced antibody affinity in sublethally irradiated mice and bone marrow chimeras

    Sublethally irradiated mice primed with dinitrophenyl (Dnp)-keyhole limpet hemocyanin immediately after irradiation or 30 days later and subsequently boosted with a second injection of antigen displayed a secondary response to Dnp characterized by antibody affinity greater than that in unirradiated controls. Also, in radiation chimeras primed with Dnp-keyhole limpet hemocyanin 120 days after syngeneic or allogeneic bone marrow transplantation the antibodies against Dnp produced after boosting were of higher affinity than the antibodies raised in normal mice. These findings are tentatively attributed to lack of suppressor thymus-derived lymphocytes (T cells) in sublethally irradiated mice and bone marrow chimeras, in which the enhanced ability to produce antibodies of high affinity may compensate for quantitative defects of the immune system

  8. On the application of Chimera/unstructured hybrid grids for conjugate heat transfer

    Kao, Kai-Hsiung; Liou, Meng-Sing

    1995-01-01

    A hybrid grid system that combines the Chimera overset grid scheme and an unstructured grid method is developed to study fluid flow and heat transfer problems. With the proposed method, the solid structural region, in which only the heat conduction is considered, can be easily represented using an unstructured grid method. As for the fluid flow region external to the solid material, the Chimera overset grid scheme has been shown to be very flexible and efficient in resolving complex configurations. The numerical analyses require the flow field solution and material thermal response to be obtained simultaneously. A continuous transfer of temperature and heat flux is specified at the interface, which connects the solid structure and the fluid flow as an integral system. Numerical results are compared with analytical and experimental data for a flat plate and a C3X cooled turbine cascade. A simplified drum-disk system is also simulated to show the effectiveness of this hybrid grid system.

  9. Chimera states in population dynamics: Networks with fragmented and hierarchical connectivities

    Hizanidis, Johanne; Panagakou, Evangelia; Omelchenko, Iryna; Schöll, Eckehard; Hövel, Philipp; Provata, Astero

    2015-07-01

    We study numerically the development of chimera states in networks of nonlocally coupled oscillators whose limit cycles emerge from a Hopf bifurcation. This dynamical system is inspired from population dynamics and consists of three interacting species in cyclic reactions. The complexity of the dynamics arises from the presence of a limit cycle and four fixed points. When the bifurcation parameter increases away from the Hopf bifurcation the trajectory approaches the heteroclinic invariant manifolds of the fixed points producing spikes, followed by long resting periods. We observe chimera states in this spiking regime as a coexistence of coherence (synchronization) and incoherence (desynchronization) in a one-dimensional ring with nonlocal coupling and demonstrate that their multiplicity depends on both the system and the coupling parameters. We also show that hierarchical (fractal) coupling topologies induce traveling multichimera states. The speed of motion of the coherent and incoherent parts along the ring is computed through the Fourier spectra of the corresponding dynamics.

  10. Suppressor cells in transplantation tolerance: the mechanisms of tolerance in radiation chimeras

    Histoincompatible-complete radiation chimeras, after resolving acute graft-vs-host (GVHD), establish specific tolerance to host and donor alloantigens. This tolerance can be perturbed with immunosuppressive agents and infusions of small numbers of donor-type cells with infusions of massive numbers of donor-type cells, or with infusions of a small number of donor-type cells, that were sensitized against host antigens prior to transfer. These chimeras possess T lymphocytes in the spleen that specifically suppress donor to host mixed lymphocyte reactions and adoptively transfer suppression of GVHD to secondary hosts. Nylon-wool fractionation of chimeric spleen cells restores the response of chimeric lymphocytes to host alloantigens, suggesting that transplantation tolerance is not attributable to clonal deletion but the activity of nylon-wool-adherent T suppressor spleen cells

  11. Suppressor cells in transplantation tolerance II. Maturation of suppressor cells in the bone marrow chimera

    Histoincompatible bone marrow allografts were established in lethally irradiated rats. At various times after transplantation, the spleen cells were harvested, subjected to mixed lymphocyte cultures, and assayed for suppressor cells in vitro and in vivo by adoptive transfer studies. Alloantigen-nonspecific suppressor cells appeared in the chimera at 40 days after grafting, coinciding with the resolution of graft-versus-host disease (GVHD). At 250 days the nonspecific suppressor cells were replaced by suppressor cells specifically suppressing donor-versus-host alloantigen responses. At 720 days suppressor cells could no longer be identified by in vitro methods but were identified by in vivo adoptive transfer of transplantation tolerance. After injection of host-type antigen into chimeras, the suppressor cells could be again demonstrated by in vitro methods

  12. Suppressor cells in transplantation tolerance. II. maturation of suppressor cells in the bone marrow chimera

    Histoincompatible bone marrow allografts were established in lethally irradiated rats. At various times after transplantation, the spleen cells were harvested, subjected to mixed lymphocyte cultures, and assayed for suppressor cells in vitro and in vivo by adoptive transfer studies. Alloantigen-nonspecific suppressor cells appeared in the chimera at 40 days after grafting, coinciding with the resolution of graft-versus-host disease (GVHD). At 250 days the nonspecific suppressor cells were replaced by suppressor cells specifically suppressing donor-versus-host alloantigen responses. At 720 days suppressor cells could no longer be identified by in vitro methods but were identified by in vivo adoptive transfer of transplantation tolerance. After injection of host-type antigen into chimeras, the suppressor cells could be again demonstrated by in vitro methods

  13. Numerical solution of the full potential equation using a chimera grid approach

    Holst, Terry L.

    1995-01-01

    A numerical scheme utilizing a chimera zonal grid approach for solving the full potential equation in two spatial dimensions is described. Within each grid zone a fully-implicit approximate factorization scheme is used to advance the solution one interaction. This is followed by the explicit advance of all common zonal grid boundaries using a bilinear interpolation of the velocity potential. The presentation is highlighted with numerical results simulating the flow about a two-dimensional, nonlifting, circular cylinder. For this problem, the flow domain is divided into two parts: an inner portion covered by a polar grid and an outer portion covered by a Cartesian grid. Both incompressible and compressible (transonic) flow solutions are included. Comparisons made with an analytic solution as well as single grid results indicate that the chimera zonal grid approach is a viable technique for solving the full potential equation.

  14. Application of a chimera technique to the computation of subsonic and transonic bi-airfoil flows

    Yagua, L.C.Q.; Koren, Barry

    2004-01-01

    This paper describes the application of a composite overset-grid technique to flow computations around a two-dimensional bi-plane. The flow is described by the steady, 2D, compressible Euler equations of gas dynamics. The discretization method used is a central finite-difference method with artificial dissipation. The overset-grid technique is of chimera-type and the bi-plane a bi-NACA0012 airfoil.

  15. Capturing the Chimera: Ideology and Persuasion in the Rhetoric of Soulforce

    Null, Matthew Todd

    2008-01-01

    Capturing the Chimera: Ideology and Persuasion in the Rhetoric of Soulforce Matthew Todd Null (ABSTRACT) For more than half a century, gay rights organizations have sought cultural and political equality for lesbian, gay, bisexual, and transgender individuals in society. The organization Soulforce continues that legacy, but from a distinctive perspective. Soulforce, has positioned itself in a unique playing field by speaking directly to religious leaders and organizations in ...

  16. Chimera patterns induced by distance-dependent power-law coupling in ecological networks

    Banerjee, Tanmoy; Dutta, Partha Sharathi; Zakharova, Anna; Schoell, Eckehard

    2016-01-01

    This paper reports the occurrence of several chimera patterns and the associated transitions among them in a network of coupled oscillators, which are connected by a long range interaction that obeys a distance-dependent power law. This type of interaction is common in physics and biology and constitutes a general form of coupling scheme, where by tuning the power-law exponent of the long range interaction the coupling topology can be varied from local via nonlocal to global coupling. To expl...

  17. Chimera states in population dynamics: networks with fragmented and hierarchical connectivities

    Hizanidis, Johanne; Panagakou, Evangelia; Omelchenko, Iryna; Schoell, Eckehard; Hoevel, Philipp; Provata, Astero

    2015-01-01

    We study numerically the development of chimera states in networks of nonlocally coupled oscillators whose limit cycles emerge from a Hopf bifurcation. This dynamical system is inspired from population dynamics and consists of three interacting species in cyclic reactions. The complexity of the dynamics arises from the presence of a limit cycle and four fixed points. When the bifurcation parameter increases away from the Hopf bifurcation the trajectory approaches the heteroclinic invariant ma...

  18. MODELS FOR MOUSE CHIMERA PRODUCTION: AGGREGATION OF ES CELLS WITH CLEAVAGE STAGE EMBRYOS

    CLAUDIA STANCA; V.B. CÂRSTEA; DANIELA ILIE; ELEN GOCZA; I. VINTILĂ

    2007-01-01

    In a mutant ES cells↔ wild-type embryo chimera, ES cells behave more like epiblastcells. They can contribute to the primitive ectoderm layers, which give rise to all theembryonic tissues and some extraembryonic tissues (Beddington and Robertson,1989), but not to trophectoderm or primitive endoderm. Using transgenic ES celllines, aggregated with cleavage stage host embryo, ES cells can integrate randomlyin the embryo proper. If they will be take part in the formation of ICM (inner cellmass), i...

  19. SummonChimera infers integrated viral genomes with nucleotide precision from NGS data

    Katz, Joshua P.; Pipas, James M.

    2014-01-01

    Background Viral integration into a host genome is defined by two chimeric junctions that join viral and host DNA. Recently, computational tools have been developed that utilize NGS data to detect chimeric junctions. These methods identify individual viral-host junctions but do not associate chimeric pairs as an integration event. Without knowing the chimeric boundaries of an integration, its genetic content cannot be determined. Results Summonchimera is a Perl program that associates chimera...

  20. Does hyperbolicity impede emergence of chimera states in networks of nonlocally coupled chaotic oscillators?

    Semenova, N.; Zakharova, A.; Schöll, E.; Anishchenko, V.

    2015-11-01

    We analyze nonlocally coupled networks of identical chaotic oscillators with either time-discrete or time-continuous dynamics (Henon map, Lozi map, Lorenz system). We hypothesize that chimera states, in which spatial domains of coherent (synchronous) and incoherent (desynchronized) dynamics coexist, can be obtained only in networks of oscillators with nonhyperbolic chaotic attractors and cannot be found in networks of systems with hyperbolic chaotic attractors. This hypothesis is supported by analytical results and numerical simulations for hyperbolic and nonhyperbolic cases.

  1. Histogenesis of mouse sarcomas induced by implantation of polyvinyl chloride film in radiation chimeras

    Sarcomas were induced in CBA/CBA-T6T6 mouse radiation chimeras by implantation of polyvinyl chloride film subcutaneously 13 months after irradiation and injection of donor's bone marrow. Of the 12 tumors studied 11 had the recipient's karyotype and one the donor's. The formation of connective-tissue cells from bone-marrow precursors thus, evidently does not play an essential role in the histogenesis of sarcomas induced by plastics

  2. Impact of hyperbolicity on chimera states in ensembles of nonlocally coupled chaotic oscillators

    Semenova, N.; Zakharova, A.; Schöll, E.; Anishchenko, V.

    2016-06-01

    In this work we analyse nonlocally coupled networks of identical chaotic oscillators. We study both time-discrete and time-continuous systems (Henon map, Lozi map, Lorenz system). We hypothesize that chimera states, in which spatial domains of coherent (synchronous) and incoherent (desynchronized) dynamics coexist, can be obtained only in networks of chaotic non-hyperbolic systems and cannot be found in networks of hyperbolic systems. This hypothesis is supported by numerical simulations for hyperbolic and non-hyperbolic cases.

  3. Earthquake sequencing: chimera states with Kuramoto model dynamics on directed graphs

    Vasudevan, K.; Cavers, M.; Ware, A.

    2015-09-01

    Earthquake sequencing studies allow us to investigate empirical relationships among spatio-temporal parameters describing the complexity of earthquake properties. We have recently studied the relevance of Markov chain models to draw information from global earthquake catalogues. In these studies, we considered directed graphs as graph theoretic representations of the Markov chain model and analyzed their properties. Here, we look at earthquake sequencing itself as a directed graph. In general, earthquakes are occurrences resulting from significant stress interactions among faults. As a result, stress-field fluctuations evolve continuously. We propose that they are akin to the dynamics of the collective behavior of weakly coupled non-linear oscillators. Since mapping of global stress-field fluctuations in real time at all scales is an impossible task, we consider an earthquake zone as a proxy for a collection of weakly coupled oscillators, the dynamics of which would be appropriate for the ubiquitous Kuramoto model. In the present work, we apply the Kuramoto model with phase lag to the non-linear dynamics on a directed graph of a sequence of earthquakes. For directed graphs with certain properties, the Kuramoto model yields synchronization, and inclusion of non-local effects evokes the occurrence of chimera states or the co-existence of synchronous and asynchronous behavior of oscillators. In this paper, we show how we build the directed graphs derived from global seismicity data. Then, we present conditions under which chimera states could occur and, subsequently, point out the role of the Kuramoto model in understanding the evolution of synchronous and asynchronous regions. We surmise that one implication of the emergence of chimera states will lead to investigation of the present and other mathematical models in detail to generate global chimera-state maps similar to global seismicity maps for earthquake forecasting studies.

  4. Mass and charge identification of fragments detected with the Chimera Silicon-CsI(Tl) telescopes

    Le Neindre, N

    2002-01-01

    Mass and charge identification of charged products detected with Silicon-CsI(Tl) telescopes of the Chimera apparatus is presented. An identification function, based on the Bethe-Bloch formula, is used to fit empirical correlation between Delta E and E ADC readings, in order to determine, event by event, the atomic and mass numbers of the detected charged reaction products prior to energy calibration.

  5. Mass and charge identification of fragments detected with the Chimera Silicon-CsI(Tl) telescopes

    Neindre, N. Le; collaboration, for REVERSE

    2001-01-01

    Mass and charge identification of charged products detected with Silicon-CsI(Tl) telescopes of the Chimera apparatus is presented. An identification function, based on the Bethe-Bloch formula, is used to fit empirical correlation between Delta E and E ADC readings, in order to determine, event by event, the atomic and mass numbers of the detected charged reaction products prior to energy calibration.

  6. Mass and charge identification of fragments detected with the Chimera Silicon-CsI(Tl) telescopes

    Le Neindre, N.; Alderighi, M.; Anzalone, A.; Barnà, R.; Bartolucci, M.; Berceanu, I.; Borderie, B.; Bougault, R.; Bruno, M.; Cardella, G.; Cavallaro, S.; D'Agostino, M.; Dayras, R.; de Filippo, E.; de Pasquale, D.; Geraci, E.; Giustolisi, F.; Grzeszczuk, A.; Guazzoni, P.; Guinet, D.; Iacono-Manno, M.; Italiano, A.; Kowalski, S.; Lanchais, A.; Lanzanó, G.; Lanzalone, G.; Li, S.; Lo Nigro, S.; Maiolino, C.; Manfredi, G.; Moisa, D.; Pagano, A.; Papa, M.; Paduszynski, T.; Petrovici, M.; Piasecki, E.; Pirrone, S.; Politi, G.; Pop, A.; Porto, F.; Rivet, M. F.; Rosato, E.; Russo, S.; Sambataro, S.; Sechi, G.; Simion, V.; Sperduto, M. L.; Steckmeyer, J. C.; Sutera, C.; Trifirò, A.; Tassan-Got, L.; Trimarchi, M.; Vannini, G.; Vigilante, M.; Wilczynski, J.; Wu, H.; Xiao, Z.; Zetta, L.; Zipper, W.

    2002-09-01

    Mass and charge identification of charged products detected with Silicon-CsI(Tl) telescopes of the Chimera apparatus are presented. An identification function, based on the Bethe-Bloch formula, is used to fit empirical correlations between ΔE and E ADC readings, in order to determine, event by event, the atomic and mass numbers of the detected charged reaction products prior to energy calibration.

  7. EXAMINATION OF THE GERM CELL CHIMERA FORMING POTENTIAL OF MOUSE EMBRYONIC STEM CELLS

    CÂRSTEA V. B

    2007-01-01

    Full Text Available The aim of this study was to examine the factors, which influence the chimeraforming potential of mouse embryonic stem cells (ES cells. In our work, we examinethe chimera producing ability of R1 and R1/E mouse ES cell lines. We found that thepassage number affects chimera-forming capability of the ES cells. With theincreasing of the passage number, it could be getting less chimera animal, and onlythe R1/E ES cell line derived cells could contribute to the germ cells. At first, wecompared the marker of pluripotency using immunostaining and RT PCR, but wecould not find any difference between the R1 and R1/E cell in this way. Atchromosome analysis, we found, that the number of aneuploid cells, in R1 ES cellline, dramatically increased after 10 passages. We thought that the reason is thatduring the cell division Y chromosome could not arrange correctly between the twonewly derived progeny cells. To prove our conception, we made X and YchromosomeFISH analyses. We found, that the aneuploid R1 and R1/E ES cellscontain only one X and one Y chromosome, so not the loss of Y chromosome causethe problem at the germ cell formation. At last, we made the karyotypeanalysis of R1 and R1/E ES cells at different passages. The karyotype analysisdemonstrated that in the case of R1 ES cell line, the 41 and 42-chromosomecontaining cells hold trisomy. With the increasing of the passages number, thenumber of trisomy containing aneuploid cells increased. The aneuploid ES cells cancontribute to the different tissuses of chimera animals, but cannot form viable germcells.

  8. EXAMINATION OF THE GERM CELL CHIMERA FORMING POTENTIAL OF MOUSE EMBRYONIC STEM CELLS

    V.B. CÂRSTEA

    2013-12-01

    Full Text Available The aim of this study was to examine the factors, which influence the chimeraforming potential of mouse embryonic stem cells (ES cells. In our work, we examinethe chimera producing ability of R1 and R1/E mouse ES cell lines. We found that thepassage number affects chimera-forming capability of the ES cells. With theincreasing of the passage number, it could be getting less chimera animal, and onlythe R1/E ES cell line derived cells could contribute to the germ cells. At first, wecompared the marker of pluripotency using immunostaining and RT PCR, but wecould not find any difference between the R1 and R1/E cell in this way. Atchromosome analysis, we found, that the number of aneuploid cells, in R1 ES cellline, dramatically increased after 10 passages. We thought that the reason is thatduring the cell division Y chromosome could not arrange correctly between the twonewly derived progeny cells. To prove our conception, we made X and YchromosomeFISH analyses. We found, that the aneuploid R1 and R1/E ES cellscontain only one X and one Y chromosome, so not the loss of Y chromosome causethe problem at the germ cell formation. At last, we made the karyotypeanalysis of R1 and R1/E ES cells at different passages. The karyotype analysisdemonstrated that in the case of R1 ES cell line, the 41 and 42-chromosomecontaining cells hold trisomy. With the increasing of the passages number, thenumber of trisomy containing aneuploid cells increased. The aneuploid ES cells cancontribute to the different tissuses of chimera animals, but cannot form viable germcells.

  9. Human-animal chimeras for vaccine development: an endangered species or opportunity for the developing world?

    Daar Abdallah S; Singer Peter A; Bhan Anant

    2010-01-01

    Abstract Background In recent years, the field of vaccines for diseases such as Human Immunodeficiency Virus (HIV) which take a heavy toll in developing countries has faced major failures. This has led to a call for more basic science research, and development as well as evaluation of new vaccine candidates. Human-animal chimeras, developed with a 'humanized' immune system could be useful to study infectious diseases, including many neglected diseases. These would also serve as an important t...

  10. Pichia pastoris as a host for secretion of toxic saporin chimeras.

    Lombardi, Alessio; Bursomanno, Sara; Lopardo, Teresa; Traini, Roberta; Colombatti, Marco; Ippoliti, Rodolfo; Flavell, David J; Flavell, Sopsamorn U; Ceriotti, Aldo; Fabbrini, Maria Serena

    2010-01-01

    Most of the targeting moieties, such as antibody fragments or growth factor domains, used to construct targeted toxins for anticancer therapy derive from secretory proteins. These normally fold in the oxidative environment of the endoplasmic reticulum, and hence their folding in bacterial cells can be quite inefficient. For instance, only low amounts of properly folded antimetastatic chimera constituted by the amino-terminal fragment of human urokinase (ATF) fused to the plant ribosome-inactivating protein saporin could be recovered. ATF-saporin was instead secreted efficiently when expressed in eukaryotic cells protected from autointoxication with neutralizing anti-saporin antibodies. Pichia pastoris is a microbial eukaryotic host where these domains can fold into a transport-competent conformation and reach the extracellular medium. We show here that despite some host toxicity codon-usage optimization greatly increased the expression levels of active saporin but not those of an active-site mutant SAP-KQ in GS115 (his4) strain. The lack of any toxicity associated with expression of the latter confirmed that toxicity is due to saporin catalytic activity. Nevertheless, GS115 (his4) cells in flask culture secreted 3.5 mg/L of a histidine-tagged ATF-saporin chimera showing an IC(50) of 6 x 10(-11) M against U937 cells, thus demonstrating the suitability of this expression platform for secretion of toxic saporin-based chimeras. PMID:19786581

  11. Chimera grids in the simulation of three-dimensional flowfields in turbine-blade-coolant passages

    Stephens, M. A.; Rimlinger, M. J.; Shih, T. I.-P.; Civinskas, K. C.

    1993-01-01

    When computing flows inside geometrically complex turbine-blade coolant passages, the structure of the grid system used can affect significantly the overall time and cost required to obtain solutions. This paper addresses this issue while evaluating and developing computational tools for the design and analysis of coolant-passages, and is divided into two parts. In the first part, the various types of structured and unstructured grids are compared in relation to their ability to provide solutions in a timely and cost-effective manner. This comparison shows that the overlapping structured grids, known as Chimera grids, can rival and in some instances exceed the cost-effectiveness of unstructured grids in terms of both the man hours needed to generate grids and the amount of computer memory and CPU time needed to obtain solutions. In the second part, a computational tool utilizing Chimera grids was used to compute the flow and heat transfer in two different turbine-blade coolant passages that contain baffles and numerous pin fins. These computations showed the versatility and flexibility offered by Chimera grids.

  12. Allogeneic radiation chimeras respond to TNP-modified donor and host targets

    Tolerance to major histocompatibility antigens as well as the ability to mount a cytotoxic response to hapten-modified cells of bone marrow donor and host origin was studied in allogeneic radiation chimeras. Lethally irradiated (C57BL/6 x DBA/2)F1 hosts reconstituted with anti-Thy 1.2 + C-treated bone marrow from (C57BL/6 x CBA)F1 mice showed tolerance to the MHC antigens of the three parental strains as measured by MLC and CML assay. The chimeras responded normally to unrelated allogeneic cells. Chimeric animals generated a cytotoxic response to hapten-modified cells of both donor (CBA) and host (DBA/2) haplotypes, as well as to C57BL/6, demonstrating that tolerance to the hapten-presenting host haplotype is sufficient to allow a cytotoxic antihapten response, and that processing through a semiallogeneic host environment does not affect the ability to generate a response to hapten in conjunction with self-determinants. Chimeras failed to mount a cytotoxic response to hapten presented on nontolerated allogeneic spleen cells

  13. Histopathological changes in exocrine glands of murine transplantation chimeras. II: Sjögren's syndrome-like exocrinopathy in mice without lupus nephritis. A model of primary Sjögren's syndrome

    Ussing, Anne Phaff; Prause, J.U.; Sørensen, Inger;

    1992-01-01

    Autoimmune disease, primary Sjögren's syndrome, transplantation chimeras, experimental model, exocrinopathy, inbred mouse strains......Autoimmune disease, primary Sjögren's syndrome, transplantation chimeras, experimental model, exocrinopathy, inbred mouse strains...

  14. Sequential analysis of the virus-immune responder characteristics of thymocytes from F1→parent radiation chimeras

    The virus-immune responder characteristics of thymocytes, spleen and lymph node (LN) cells from (P1 x P2)F1→P1 radiation chimeras have been examined sequentially at weekly intervals. Adoptively-transferred thymocytes generate strong cytotoxic thymus-derived lymphocyte (CTL) responses from 28 to 100 days after reconstitution with bone marrow, which are almost invariably restricted to recognition of virus presented in the context of P1. This pattern of H-2 restriction is also maintained for spleen and LN cells from the [(H-2sup(kxd)F1→H-2sup(k)] and [(H-2sup(kxb)F1→H-2sup(k)] combinations but there is random emergence of reactivity to H-2sup(k)+virus for peripheral lymphoid cells from [(H-2sup(kxb)F1→H-2sup(b)] chimeras. Treatment of established [(P1xP2)]F1→P1] chimeras with a low dose of cyclophosphamide (Cy) did not lead to the emergence of significant CTL effector function for P2 + virus. Also, administration of a large dose of Cy prior to irradiation of the chimera recipients did not modify the H-2 restriction profile of the chimera, though the level of CTL responsiveness associated with the appropriate H-2 type was apparently enhanced. (Auth.)

  15. PCSK9 prosegment chimera as novel inhibitors of LDLR degradation.

    Yascara Grisel Luna Saavedra

    Full Text Available The proprotein convertase PCSK9, a target for the treatment of hypercholesterolemia, is a negative regulator of the LDL receptor (LDLR leading to its degradation in endosomes/lysosomes and up-regulation of plasma LDL-cholesterol levels. The proprotein convertases, a family of nine secretory serine proteases, are first synthesized as inactive zymogens. Except for PCSK9, all other convertases are activated following the autocatalytic excision of their inhibitory N-terminal prosegment. PCSK9 is unique since the mature enzyme exhibits a cleaved prosegment complexed with the catalytic subunit and has no protease activity towards other substrates. Similar to other convertases, we hypothesized that the in trans presence of the PCSK9 prosegment would interfere with PCSK9's activity on the LDLR. Since the prosegment cannot be secreted alone, we engineered a chimeric protein using the Fc-region of human IgG1 fused to the PCSK9 prosegment. The expression of such Fcpro-fusion protein in HEK293 and HepG2 cells resulted in a secreted protein that binds PCSK9 and markedly inhibits its activity on the LDLR. This was observed by either intracellular co-expression of PCSK9 and Fcpro or by an extracellular in vitro co-incubation of Fcpro with PCSK9. Structure-function studies revealed that the inhibitory function of Fcpro does not require the acidic N-terminal stretch (residues 31-58 nor the C-terminal Gln 152 of the prosegment. Fcpro likely interacts with the prosegment and/or catalytic subunit of the prosegment≡PCSK9 complex thereby allosterically modulating its function. Our data suggest a novel strategic approach for the design and isolation of PCSK9 inhibitors.

  16. Commentary on 'The arms of the chimeras' by Béatrice Ithier.

    Abram, Jan

    2016-04-01

    In this Commentary I will first of all summarise my understanding of the proposal set out by Béatrice Ithier concerning her concept of the 'chimera'. The main part of my essay will focus on Ithier's claim that her concept of the chimera could be described as a 'mental squiggle' because it corresponds to Winnicott's work illustrated in his book 'Therapeutic Consultations' (1971). At the core of Ithier's chimera is the notion of a traumatic link between analyst and patient, which is the reason she enlists the work of Winnicott. I will argue, however, that Ithier's claim is based on a misperception of the theory that underpins Winnicott's therapeutic consultations because, different from Ithier's clinical examples of work with traumatised patients, Winnicott is careful to select cases who are from an 'average expectable environment' i.e. a good enough family. Moreover, Winnicott does not refer to any traumatic affinity with his patients, or to experiencing a quasi-hallucinatory state of mind during the course of the consultations. These aspects are not incorporated into his theory. In contrast (to the concept Ithier attempts to advance), Winnicott's squiggle game constitutes an application of psychoanalysis intended as a diagnostic consultation. In that sense Winnicott's therapeutic consultations are comparable with the ordinary everyday work between analyst and analysand in a psychoanalytic treatment. My Commentary concludes with a question concerning the distinction between the ordinary countertransference in working with patients who are thinking symbolically in contrast to an extraordinary countertransference that I suggest is more likely to arise with patients who are traumatised and thus functioning at a borderline or psychotic level. PMID:27112824

  17. Chimeras taking shape: potential functions of proteins encoded by chimeric RNA transcripts.

    Frenkel-Morgenstern, Milana; Lacroix, Vincent; Ezkurdia, Iakes; Levin, Yishai; Gabashvili, Alexandra; Prilusky, Jaime; Del Pozo, Angela; Tress, Michael; Johnson, Rory; Guigo, Roderic; Valencia, Alfonso

    2012-07-01

    Chimeric RNAs comprise exons from two or more different genes and have the potential to encode novel proteins that alter cellular phenotypes. To date, numerous putative chimeric transcripts have been identified among the ESTs isolated from several organisms and using high throughput RNA sequencing. The few corresponding protein products that have been characterized mostly result from chromosomal translocations and are associated with cancer. Here, we systematically establish that some of the putative chimeric transcripts are genuinely expressed in human cells. Using high throughput RNA sequencing, mass spectrometry experimental data, and functional annotation, we studied 7424 putative human chimeric RNAs. We confirmed the expression of 175 chimeric RNAs in 16 human tissues, with an abundance varying from 0.06 to 17 RPKM (Reads Per Kilobase per Million mapped reads). We show that these chimeric RNAs are significantly more tissue-specific than non-chimeric transcripts. Moreover, we present evidence that chimeras tend to incorporate highly expressed genes. Despite the low expression level of most chimeric RNAs, we show that 12 novel chimeras are translated into proteins detectable in multiple shotgun mass spectrometry experiments. Furthermore, we confirm the expression of three novel chimeric proteins using targeted mass spectrometry. Finally, based on our functional annotation of exon organization and preserved domains, we discuss the potential features of chimeric proteins with illustrative examples and suggest that chimeras significantly exploit signal peptides and transmembrane domains, which can alter the cellular localization of cognate proteins. Taken together, these findings establish that some chimeric RNAs are translated into potentially functional proteins in humans. PMID:22588898

  18. Phenotypic characterization of early events of thymus repopulation in radiation bone marrow chimeras

    The phenotype of murine thymocytes repopulating the thymus of radiation bone marrow chimeras shortly after irradiation and bone marrow reconstitution was analyzed by immunofluorescence and flow microfluorometry. Thymuses in these chimeras, while essentially devoid of lymphoid cells at day 7, were repopulated by days 10 to 12 after irradiation. It was found that this initial repopulation arose from a radioresistant intrathymic precursor that expanded to an almost complete complement of host-type thymocytes. However, these host-derived thymocytes were unusual in that they were relatively deficient in Lyt 1+2- and peanut agglutinin ''dull'' cells as compared with normal thymocytes. Donor bone-marrow-derived cells first appeared in the irradiated chimeric thymuses between days 12 and 15 after irradiation and bone marrow transfer. By day 19, chimeric thymuses contained more than 98% donor cells. This course was identical for three chimeric combinations, each made across different genetic barriers. In contrast to the cells that populate the fetal thymus during normal ontogeny, the first donor bone-marrow-derived cells that can be detected within the irradiated chimeric thymuses already expressed phenotypically normal adult T cell subpopulations in that they contained significant numbers both of Lyt 1+2- and of Lyt 1+2+ thymocytes. Thus, the Lyt phenotype of donor cells that initially repopulate an adult thymus after irradiation is markedly different from the Lyt phenotype of cells that initially populate the fetal thymus. The differences between adult and fetal thymic development that are observed in radiation bone marrow chimeras may be important in our understanding of T cell differentiation in these animals

  19. Anti-bacterial immunity to Listeria monocytogenes in allogeneic bone marrow chimera in mice

    Protection and delayed-type hypersensitivity (DTH) to the facultative intracellular bacterium Listeria monocytogenes (L.m.) were studied in allogeneic and syngeneic bone marrow chimeras. Lethally irradiated AKR (H-2k) mice were successfully reconstituted with marrow cells from C57BL/10 (B10) (H-2b), B10 H-2-recombinant strains or syngeneic mice. Irradiated AKR mice reconstituted with marrow cells from H-2-compatible B10.BR mice, [BR----AKR], as well as syngeneic marrow cells, [AKR----AKR], showed a normal level of responsiveness to the challenge stimulation with the listeria antigens when DTH was evaluated by footpad reactions. These mice also showed vigorous activities in acquired resistance to the L.m. By contrast, chimeric mice that had total or partial histoincompatibility at the H-2 determinants between donor and recipient, [B10----AKR], [B10.AQR----AKR], [B10.A(4R)----AKR], or [B10.A(5R)----AKR], were almost completely unresponsive in DTH and antibacterial immunity. However, when [B10----AKR] H-2-incompatible chimeras had been immunized with killed L.m. before challenge with live L.m., these mice manifested considerable DTH and resistance to L.m. These observations suggest that compatibility at the entire MHC between donor and recipient is required for bone marrow chimeras to be able to manifest DTH and protection against L.m. after a short-term immunization schedule. However, this requirement is overcome by a preceding or more prolonged period of immunization with L.m. antigens. These antigens, together with marrow-derived antigen-presenting cells, can then stimulate and expand cell populations that are restricted to the MHC (H-2) products of the donor type

  20. Formation of germline chimera Gaok chicken used circulation primordial germ cells (circulation PGCs fresh and thawed

    Kostaman T

    2014-03-01

    Full Text Available Formation of germline chimeras by transfer of chicken primordial germ cells (PGCs is one of the effective techniques for preservation and regeneration of genetic resources in chickens. This study attempted to form germline chimeras of Gaok chicken buy purifying circulated PGCs of donor embryo before it is transferred to the recipient (White Leghorn chickens=WL and studied the ability of recipient embryo on survival in incubators, and hatchability. This study used 200 fertile eggs of Gaok and 90 fertile WL breed all of the eggs was incubated at 380C and 60% humidity in a portable incubator. PGCs-circulation of the blood collected Gaok embryos at stage 14-16 were taken from the dorsal aorta, and then purified by centrifugation method using nycodenz. PGCs-circulation results further purification frozen in liquid nitrogen before being transferred to the recipient embryo. The results showed that for the development of embryos transferred to the fresh circulation of PGCs-circulation as many as 25 cells can survive up to day 14, while one of the transferred of 50 and 100 cells into recipient embryos was hatched (10%. On the contrari recipient embryos that are transferred to the frozen PGCs-circulation the embryos development was shorter, and only survived until day 10th (treatment 25 cells, day 14th (treatment of 50 cells and day 17th (treatment of 100 cells. It is concluded that the amount of PGCs-circulation embryos transferred to the recipient is one factor that influence the success of the development germline chimeras.

  1. Peptide-steroids chimeras synthesis and visualization of their binding to the rat brain slices

    Jurasek, M.; Flegel, Martin; Skopek, P.; Flegelová, Z.; Drasar, P.; Hynie, S.; Klenerová, V.

    2012-01-01

    Roč. 18, S1 (2012), S123-S123. ISSN 1075-2617. [European Peptide Symposium /32./. 02.09.2012-07.09.2012, Athens] R&D Projects: GA MŠk(CZ) 7E11071 EU Projects: European Commission(XE) 245122 - DINAMO Grant ostatní: PRVOUK(CZ) P25/LF1/2; GA UK(CZ) 85210; GA UK(CZ) SVV 264514; GA AV ČR(CZ) KAN200100801 Institutional research plan: CEZ:AV0Z40550506 Keywords : oxytocin * chimeras * steroids * binding sites Subject RIV: CE - Biochemistry

  2. Explosive synchronization in clustered scale-free networks: Revealing the existence of chimera state

    Berec, V.

    2016-02-01

    The collective dynamics of Kuramoto oscillators with a positive correlation between the incoherent and fully coherent domains in clustered scale-free networks is studied. Emergence of chimera states for the onsets of explosive synchronization transition is observed during an intermediate coupling regime when degree-frequency correlation is established for the hubs with the highest degrees. Diagnostic of the abrupt synchronization is revealed by the intrinsic spectral properties of the network graph Laplacian encoded in the heterogeneous phase space manifold, through extensive analytical investigation, presenting realistic MC simulations of nonlocal interactions in discrete time dynamics evolving on the network.

  3. Multitasking for flows about multiple body configurations using the chimera grid scheme

    Dougherty, F. C.; Morgan, R. L.

    1987-01-01

    The multitasking of a finite-difference scheme using multiple overset meshes is described. In this chimera, or multiple overset mesh approach, a multiple body configuration is mapped using a major grid about the main component of the configuration, with minor overset meshes used to map each additional component. This type of code is well suited to multitasking. Both steady and unsteady two dimensional computations are run on parallel processors on a CRAY-X/MP 48, usually with one mesh per processor. Flow field results are compared with single processor results to demonstrate the feasibility of running multiple mesh codes on parallel processors and to show the increase in efficiency.

  4. Transfer of experimental allergic encephalomyelitis to bone marrow chimeras. Endothelial cells are not a restricting element

    The adoptive transfer of clinical and histopathologic signs of experimental allergic encephalomyelitis (EAE) requires MHC compatibility between cell donor and cell recipient. The results of adoptive transfer studies using F1 to parent bone marrow chimeras as recipients of parental-derived BP-sensitive spleen cells indicate that this restriction is not expressed at the level of the endothelial cell but is confined to the cells of bone marrow derivation. Furthermore, these results indicate that the development of EAE is not dependent on the activity of MHC-restricted cytotoxic cells

  5. Self-renewal of pulmonary alveolar macrophages: evidence from radiation chimera studies

    Radiation-induced chimeric mice were used to study the origin of pulmonary alveolar macrophages. Unlike in other studies, these radiation chimeras were prepared by using a special fractionated irradiation regimen to minimize the killing of alveolar macrophage colony-forming cells, putative local stem cells. For this study CBA mice with or without T6 chromosome marker were used. Under this experimental condition, the majority of alveolar macrophages in mitosis are of host origin even after 45 weeks. These data suggest that alveolar macrophages are a self-renewing population under normal steady-state conditions

  6. Core Collapse Supernovae using CHIMERA: Gravitational Radiation from Non-Rotating Progenitors

    Yakunin, Konstantin; Mezzacappa, Anthony; Bruenn, Stephen W; Lee, Ching-Tsai; Chertkow, Merek A; Hix, W Raphael; Blondin, John M; Lentz, Eric J; Messer, O E Bronson; Yoshida, Shin

    2010-01-01

    The CHIMERA code is a multi-dimensional multi-physics engine dedicated primarily to the simulation of core collapse supernova explosions. One of the most important aspects of these explosions is their capacity to produce gravitational radiation that is detectable by Earth-based laser-interferometric gravitational wave observatories such as LIGO and VIRGO. We present here preliminary gravitational signatures of two-dimensional models with non-rotating progenitors. These simulations exhibit explosions, which are followed for more than half a second after stellar core bounce.

  7. Acute serum amyloid A induces migration, angiogenesis, and inflammation in synovial cells in vitro and in a human rheumatoid arthritis/SCID mouse chimera model.

    Connolly, Mary

    2010-06-01

    Serum amyloid A (A-SAA), an acute-phase protein with cytokine-like properties, is expressed at sites of inflammation. This study investigated the effects of A-SAA on chemokine-regulated migration and angiogenesis using rheumatoid arthritis (RA) cells and whole-tissue explants in vitro, ex vivo, and in vivo. A-SAA levels were measured by real-time PCR and ELISA. IL-8 and MCP-1 expression was examined in RA synovial fibroblasts, human microvascular endothelial cells, and RA synovial explants by ELISA. Neutrophil transendothelial cell migration, cell adhesion, invasion, and migration were examined using transwell leukocyte\\/monocyte migration assays, invasion assays, and adhesion assays with or without anti-MCP-1\\/anti-IL-8. NF-kappaB was examined using a specific inhibitor and Western blotting. An RA synovial\\/SCID mouse chimera model was used to examine the effects of A-SAA on cell migration, proliferation, and angiogenesis in vivo. High expression of A-SAA was demonstrated in RA patients (p < 0.05). A-SAA induced chemokine expression in a time- and dose-dependent manner (p < 0.05). Blockade with anti-scavenger receptor class B member 1 and lipoxin A4 (A-SAA receptors) significantly reduced chemokine expression in RA synovial tissue explants (p < 0.05). A-SAA induced cell invasion, neutrophil-transendothelial cell migration, monocyte migration, and adhesion (all p < 0.05), effects that were blocked by anti-IL-8 or anti-MCP-1. A-SAA-induced chemokine expression was mediated through NF-kappaB in RA explants (p < 0.05). Finally, in the RA synovial\\/SCID mouse chimera model, we demonstrated for the first time in vivo that A-SAA directly induces monocyte migration from the murine circulation into RA synovial grafts, synovial cell proliferation, and angiogenesis (p < 0.05). A-SAA promotes cell migrational mechanisms and angiogenesis critical to RA pathogenesis.

  8. Resistance to infection with Eimeria vermiformis in mouse radiation chimeras is determined by donor bone-marrow cells.

    Joysey, H S; Wakelin, D; Rose, M E

    1988-01-01

    The course of infection with Eimeria vermiformis was determined in BALB/b, BALB/c, and C57BL/10ScSn (B10) mice and in radiation chimeras prepared from the H-2-compatible BALB/b and B10 mice. The BALB strains, irrespective of H-2 haplotype, were resistant, the B10 mice were susceptible, and in the chimeras infection was characterized by the genotype of the donated bone-marrow cells and not by the phenotype of the recipient. Thus, the genetic control of relative resistance or susceptibility to ...

  9. Resistance to infection with Eimeria vermiformis in mouse radiation chimeras is determined by donor bone-marrow cells

    The course of infection with Eimeria vermiformis was determined in BALB/b, BALB/c, and C57BL/10ScSn (B10) mice and in radiation chimeras prepared from the H-2-compatible BALB/b and B10 mice. The BALB strains, irrespective of H-2 haplotype, were resistant, the B10 mice were susceptible, and in the chimeras infection was characterized by the genotype of the donated bone-marrow cells and not by the phenotype of the recipient. Thus, the genetic control of relative resistance or susceptibility to infection with this parasite is expressed through bone-marrow-derived cells

  10. CHIMERA: a 4π detector array for heavy ion reaction studies at intermediate energy. Survey and status of the project

    CHIMERA is a multi-element detector array made of 1192 Si-CsI telescopes covering the 94% of the whole solid angle that is planned to fully operate in 1998 by using the Super conducing Cyclotron beams at the LNS of Catania. Besides the usual charge identification, due to simultaneous TOF measurements, CHIMERA allows a mass identification. The high granularity reduces drastically the multiple firing and make it possible to perform an event by event analysis as required in multifragmentation process studies. The authors will discuss some results of simulations concerning the problem of the complete event reconstruction, in connection with the specific performances of the detector

  11. Interaction of growth hormone receptor/binding protein gene disruption and caloric restriction for insulin sensitivity and attenuated aging [v2; ref status: indexed, http://f1000r.es/5a7

    Oge Arum

    2015-04-01

    Full Text Available The correlation of physiological sensitivity to insulin (vis-à-vis glycemic regulation and longevity is extensively established, creating a justifiable gerontological interest on whether insulin sensitivity is causative, or even predictive, of some or all phenotypes of slowed senescence (including longevity. The growth hormone receptor/ binding protein gene-disrupted (GHR-KO mouse is the most extensively investigated insulin-sensitive, attenuated aging model. It was reported that, in a manner divergent from similar mutants, GHR-KO mice fail to respond to caloric restriction (CR by altering their insulin sensitivity. We hypothesized that maximized insulin responsiveness is what causes GHR-KO mice to exhibit a suppressed survivorship response to dietary (including caloric restriction; and attempted to refute this hypothesis by assessing the effects of CR on GHR-KO mice for varied slow-aging-associated phenotypes. In contrast to previous reports, we found GHR-KO mice on CR to be less responsive than their ad libitum (A.L. counterparts to the hypoglycemia-inducing effects of insulin. Further, CR had negligible effects on the metabolism or cognition of GHR-KO mice. Therefore, our data suggest that the effects of CR on the insulin sensitivity of GHR-KO mice do not concur with the effects of CR on the aging of GHR-KO mice.

  12. The assay of thyrotropin receptor antibodies with human TSH/LH-CG chimeric receptor expressed on chinese hamster ovary cells

    TSH/LH-CG chimera cDNA is transfected to CHO-K1 cell to obtain the chimeric receptor expressed on the cell surface. The optimal conditions for TSAb and TSBAb measurements are determined using chimeric receptors and under these conditions activity of TSAb and TSBAb in the sera of the Graves' patients. The results obtained are compared to those of TSAb assays using FRTL5 cells CHO-TSHR cells which have wild type human TSH receptor. The transfection procedure of chimeric receptor gene to CHO-K1 cells are on going. The optimal conditions for TSAb and TSBAb measurement using chimeric receptor will be determined after success of transfection procedure. If this study is successfully completed, not only the heterogeneity of Graves. IgG but also pathogenesis of Graves' disease will be elucidated. (author). 25 refs

  13. The assay of thyrotropin receptor antibodies with human TSH/LH-CG chimeric receptor expressed on chinese hamster ovary cells

    Yi, Ka Hee; Kim, Chang Min [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    1996-12-01

    TSH/LH-CG chimera cDNA is transfected to CHO-K1 cell to obtain the chimeric receptor expressed on the cell surface. The optimal conditions for TSAb and TSBAb measurements are determined using chimeric receptors and under these conditions activity of TSAb and TSBAb in the sera of the Graves` patients. The results obtained are compared to those of TSAb assays using FRTL5 cells CHO-TSHR cells which have wild type human TSH receptor. The transfection procedure of chimeric receptor gene to CHO-K1 cells are on going. The optimal conditions for TSAb and TSBAb measurement using chimeric receptor will be determined after success of transfection procedure. If this study is successfully completed, not only the heterogeneity of Graves. IgG but also pathogenesis of Graves` disease will be elucidated. (author). 25 refs.

  14. Prototype and Chimera-Type Galectins in Placentas with Spontaneous and Recurrent Miscarriages.

    Unverdorben, Laura; Haufe, Thomas; Santoso, Laura; Hofmann, Simone; Jeschke, Udo; Hutter, Stefan

    2016-01-01

    Galectins are galactose binding proteins and, in addition, factors for a wide range of pathologies in pregnancy. We have analyzed the expression of prototype (gal-1, -2, -7, -10) and chimera-type (gal-3) galectins in the placenta in cases of spontaneous abortions (SPA) and recurrent abortions (RA) in the first trimester. Fifteen placental samples from healthy pregnancies were used as a control group. Nine placentas were examined for spontaneous abortions, and 12 placentas for recurrent abortions. For differentiation and evaluation of different cell types of galectin-expression in the decidua, immunofluorescence was used. For all investigated prototype galectins (gal-1, -2, -7, -10) in SPA and RA placenta trophoblast cells the expression is significantly decreased. In the decidua/extravillous trophoblast only gal-2 expression was significantly lowered, which could be connected to its role in angiogenesis. In trophoblasts in first-trimester placentas and in cases of SPA and RA, prototype galectins are altered in the same way. We suspect prototype galectins have a similar function in placental tissue because of their common biochemical structure. Expression of galectin 3 as a chimera type galectin was not found to be significantly altered in abortive placentas. PMID:27136536

  15. Proteomic Analysis Reveals the Leaf Color Regulation Mechanism in Chimera Hosta "Gold Standard" Leaves.

    Yu, Juanjuan; Zhang, Jinzheng; Zhao, Qi; Liu, Yuelu; Chen, Sixue; Guo, Hongliang; Shi, Lei; Dai, Shaojun

    2016-01-01

    Leaf color change of variegated leaves from chimera species is regulated by fine-tuned molecular mechanisms. Hosta "Gold Standard" is a typical chimera Hosta species with golden-green variegated leaves, which is an ideal material to investigate the molecular mechanisms of leaf variegation. In this study, the margin and center regions of young and mature leaves from Hosta "Gold Standard", as well as the leaves from plants after excess nitrogen fertilization were studied using physiological and comparative proteomic approaches. We identified 31 differentially expressed proteins in various regions and development stages of variegated leaves. Some of them may be related to the leaf color regulation in Hosta "Gold Standard". For example, cytosolic glutamine synthetase (GS1), heat shock protein 70 (Hsp70), and chloroplastic elongation factor G (cpEF-G) were involved in pigment-related nitrogen synthesis as well as protein synthesis and processing. By integrating the proteomics data with physiological results, we revealed the metabolic patterns of nitrogen metabolism, photosynthesis, energy supply, as well as chloroplast protein synthesis, import and processing in various leaf regions at different development stages. Additionally, chloroplast-localized proteoforms involved in nitrogen metabolism, photosynthesis and protein processing implied that post-translational modifications were crucial for leaf color regulation. These results provide new clues toward understanding the mechanisms of leaf color regulation in variegated leaves. PMID:27005614

  16. Inherited effects from irradiated mouse immature oocytes detected in aggregation embryo chimeras

    Data obtained using the mouse-preimplantation-embryo-chimera assay are presented that show a transmitted effect following low-dose irradiation of immature oocytes in vivo. Six-week-old female mice were irradiated using 137Cs-γ-rays (0.05 Gy, 0.15 Gy, and unexposed controls). At 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 weeks post exposure, the mice were mated and aggregation chimeras made from the 4-cell embryos. Three independent experiments have now been carried out, all showing a significant embryonic cell-proliferation disadvantage of the embryos obtained from the females treated 7 weeks previously, i.e., embryos from oocytes that were immature at the time of radiation exposure. No effect was detected at 1-6 weeks when embryos were obtained from maturing oocytes. Also, the effect was not seen at 8, 9, 10, 11, and 12 weeks post exposure. The implications of these results are discussed in the light of previous studies on mouse oocytes

  17. Survival of allografts from bone marrow donors in temporary dog radiation chimeras

    Complete radiation chimeras accept indefinitely a skin or a kidney graft from the bone marrow (BM) donor. The advantages of this method of inducing graft acceptance are that it does not require the use of toxic post-operative immunosuppressive agents and that the immune reactivity against antigens other than the ones carried by the BM donor remains intact. The disadvantages of this approach are that supralethal total body irradiation (TBI) causes toxicity and that allogeneic BM cells can cause lethal Graft versus Host reactions. Attempts were made to diminish the significance of these disadvantages by using lower dose TBI and giving fewer BM cells. It is shown that, in dogs, 7.5 Gy TBI followed by 4 X 108 BM cells.kg-1 body weight of a DLA identical sibling leads to the development of complete radiation chimeras. The exclusive presence of donor type haemopoiesis can be demonstrated by determinations of 'informative' genetic markers, i.e., markers that show different genotypes in donor and recipient. (Auth.)

  18. Proteomic Analysis Reveals the Leaf Color Regulation Mechanism in Chimera Hosta “Gold Standard” Leaves

    Yu, Juanjuan; Zhang, Jinzheng; Zhao, Qi; Liu, Yuelu; Chen, Sixue; Guo, Hongliang; Shi, Lei; Dai, Shaojun

    2016-01-01

    Leaf color change of variegated leaves from chimera species is regulated by fine-tuned molecular mechanisms. Hosta “Gold Standard” is a typical chimera Hosta species with golden-green variegated leaves, which is an ideal material to investigate the molecular mechanisms of leaf variegation. In this study, the margin and center regions of young and mature leaves from Hosta “Gold Standard”, as well as the leaves from plants after excess nitrogen fertilization were studied using physiological and comparative proteomic approaches. We identified 31 differentially expressed proteins in various regions and development stages of variegated leaves. Some of them may be related to the leaf color regulation in Hosta “Gold Standard”. For example, cytosolic glutamine synthetase (GS1), heat shock protein 70 (Hsp70), and chloroplastic elongation factor G (cpEF-G) were involved in pigment-related nitrogen synthesis as well as protein synthesis and processing. By integrating the proteomics data with physiological results, we revealed the metabolic patterns of nitrogen metabolism, photosynthesis, energy supply, as well as chloroplast protein synthesis, import and processing in various leaf regions at different development stages. Additionally, chloroplast-localized proteoforms involved in nitrogen metabolism, photosynthesis and protein processing implied that post-translational modifications were crucial for leaf color regulation. These results provide new clues toward understanding the mechanisms of leaf color regulation in variegated leaves. PMID:27005614

  19. Prototype and Chimera-Type Galectins in Placentas with Spontaneous and Recurrent Miscarriages

    Unverdorben, Laura; Haufe, Thomas; Santoso, Laura; Hofmann, Simone; Jeschke, Udo; Hutter, Stefan

    2016-01-01

    Galectins are galactose binding proteins and, in addition, factors for a wide range of pathologies in pregnancy. We have analyzed the expression of prototype (gal-1, -2, -7, -10) and chimera-type (gal-3) galectins in the placenta in cases of spontaneous abortions (SPA) and recurrent abortions (RA) in the first trimester. Fifteen placental samples from healthy pregnancies were used as a control group. Nine placentas were examined for spontaneous abortions, and 12 placentas for recurrent abortions. For differentiation and evaluation of different cell types of galectin-expression in the decidua, immunofluorescence was used. For all investigated prototype galectins (gal-1, -2, -7, -10) in SPA and RA placenta trophoblast cells the expression is significantly decreased. In the decidua/extravillous trophoblast only gal-2 expression was significantly lowered, which could be connected to its role in angiogenesis. In trophoblasts in first-trimester placentas and in cases of SPA and RA, prototype galectins are altered in the same way. We suspect prototype galectins have a similar function in placental tissue because of their common biochemical structure. Expression of galectin 3 as a chimera type galectin was not found to be significantly altered in abortive placentas. PMID:27136536

  20. Chronic graft-versus-host disease in the rat radiation chimera. III. Immunology and immunopathology in rapidly induced models

    Although chronic graft-versus-host disease (GVHD) frequently develops in the long-term rat radiation chimera, we present three additional models in which a histologically similar disease is rapidly induced. These include adoptive transfer of spleen and bone marrow from rats with spontaneous chronic GVHD into lethally irradiated rats of the primary host strain; sublethal irradiation of stable chimeras followed by a booster transplant; and transfer of spleen cells of chimeras recovering from acute GVHD into second-party (primary recipient strain) or third-party hosts. Some immunopathologic and immune abnormalities associated with spontaneous chronic GVHD were not observed in one or more of the induced models. Thus, IgM deposition in the skin, antinuclear antibodies, and vasculitis appear to be paraphenomena. On the other hand, lymphoid hypocellularity of the thymic medulla, immaturity of splenic follicles, and nonspecific suppressor cells were consistently present in the long term chimeras, and in all models. These abnormalities therefore may be pathogenetically important, or closely related to the development of chronic GVHD

  1. Thymectomized, irradiated, and bone marrow-reconstituted chimeras have normal cytolytic T lymphocyte precursors but a defect in lymphokine production

    A model system has been developed to study extrathymic T cell differentiation; mice have been thymectomized, lethally irradiated, and reconstituted with bone marrow cells depleted of Thy-1+ cells. After 8 wk, the spleen cells of these athymic, bone marrow-reconstituted chimeras contain Thy-1+ precytolytic T lymphocytes (CTL) that are able to respond to antigen only if supernatant from Con A-activated T cells is added to culture. The phenotype of these pre-CTL is similar to that of thymocytes, suggesting that they may be immature T cells. Initial evaluation of the CTL repertoire of these athymic mice demonstrated that the CTL generated to trinitrophenyl-modified syngeneic cells are H-2-restricted, and that the CTL generated to alloantigens have many of the cross-reactivities observed in normal mice but not in nude mice. In this report, the authors demonstrate a helper T cell defect in these thymectomized chimeras. These chimeras lack an Ly-1+ helper cell required for thymocytes to differentiate to CTL. Further studies revealed that when spleen cells from these thymectomized chimeras were stimulated with Con A, they produced normal levels of interleukin 2. However, these splenocytes were defective in the production of another factor needed for CTL differentiation

  2. A GTPase chimera illustrates an uncoupled nucleotide affinity and release rate, Providing insight into the activation mechanism

    Guilfoyle, Amy P.; Deshpande, Chandrika N.; Font Sadurni, Josep;

    2014-01-01

    GDP release, or, alternatively, the movement is a consequence of release. To gain additional insight into the sequence of events leading to GDP release, we have created a chimeric protein comprised of Escherichia coli NFeoB and the G5 loop from the human Giα1 protein. The protein chimera retains...

  3. Optimization of three-dimensional imaging on in vitro produced porcine blastocysts and chimeras for stem cell testing

    Secher, Jan Ole Bertelsen; Freude, Kristine; Li, Rong;

    2015-01-01

    is relevant for testing of presumed pluripotent stem cells. The gold standard for pluripotent stem cells is to test if the cells are capable of contributing to germline chimeras. Differential staining can be used to evaluate the possibility of chimeric contribution; if the cells are located in the...

  4. Prenatal Allospecific NK Cell Tolerance Hinges on Instructive Allorecognition through the Activating Receptor during Development.

    Alhajjat, Amir M; Strong, Beverly S; Lee, Amanda E; Turner, Lucas E; Wadhwani, Ram K; Ortaldo, John R; Heusel, Jonathan W; Shaaban, Aimen F

    2015-08-15

    Little is known about how the prenatal interaction between NK cells and alloantigens shapes the developing NK cell repertoire toward tolerance or immunity. Specifically, the effect on NK cell education arising from developmental corecognition of alloantigens by activating and inhibitory receptors with shared specificity is uncharacterized. Using a murine prenatal transplantation model, we examined the manner in which this seemingly conflicting input affects NK cell licensing and repertoire formation in mixed hematopoietic chimeras. We found that prenatal NK cell tolerance arose from the elimination of phenotypically hostile NK cells that express an allospecific activating receptor without coexpressing any allospecific inhibitory receptors. Importantly, the checkpoint for the system appeared to occur centrally within the bone marrow during the final stage of NK cell maturation and hinged on the instructive recognition of allogeneic ligand by the activating receptor rather than through the inhibitory receptor as classically proposed. Residual nondeleted hostile NK cells expressing only the activating receptor exhibited an immature, anergic phenotype, but retained the capacity to upregulate inhibitory receptor expression in peripheral sites. However, the potential for this adaptive change to occur was lost in developmentally mature chimeras. Collectively, these findings illuminate the intrinsic process in which developmental allorecognition through the activating receptor regulates the emergence of durable NK cell tolerance and establishes a new paradigm to fundamentally guide future investigations of prenatal NK cell-allospecific education. PMID:26136432

  5. Monsters, dreams and madness: Commentary on 'The arms of the chimeras'.

    Reis, Bruce

    2016-04-01

    Considering Freudian and Post-Freudian approaches to the intersubjective Beatrice Ithier puts the work of Michel de M'Uzan and Thomas Ogden in comparison. To this comparison I add a consideration of the work of Christopher Bollas. The highly creative clinical approaches these three theorists take is shown to be informed by their elaborations of the Freudian notion of unconscious communication and by new approaches to the issue of identity. Attention is paid to differentiating traumatic from fanciful chimeras; and to the experience of the analyst undergoing the sorts of transformations requisite to entering this psychic space marked by fluid exchanges of being and becoming, wherein analyst becomes patient, new subjects are created through shared dreams, and through which monsters appear. PMID:26996388

  6. THE KEY TO THE TREASURE IS THE TREASURE: BARTH’S METAFICTION IN CHIMERA

    Katarina Drzajic

    2014-11-01

    Full Text Available John Barth, one of the most prominent postmodern authors, is famous for his creative literary games: while his favorite tool, metafiction, is at times hard to comprehend, he is almost always both the writer and a character of his stories. “Everyone is necessarily the hero of his own life story,” he said, thus confirming the quite loose difference between reality and fiction in post-modernism. Bearing in mind that the story within a story is a common characteristic of his work, in this paper we shall analyze the most interesting points at which we encounter this phenomenon an d discover what actually represents the treasure in one of his most perplexing, yet incredibly captivating novels, Chimera.

  7. Two- and three-dimensional simulations of core-collapse supernovae with CHIMERA

    Lentz, Eric J; Harris, J Austin; Chertkow, Merek Austin; Hix, W Raphael; Mezzacappa, Anthony; Messer, O E Bronson; Bondin, John M; Marronetti, Pedro; Mauney, Christopher M; Yakunin, Konstantin N

    2013-01-01

    Ascertaining the core-collapse supernova mechanism is a complex, and yet unsolved, problem dependent on the interaction of general relativity, hydrodynamics, neutrino transport, neutrino-matter interactions, and nuclear equations of state and reaction kinetics. Ab initio modeling of core-collapse supernovae and their nucleosynthetic outcomes requires care in the coupling and approximations of the physical components. We have built our multi-physics CHIMERA code for supernova modeling in 1-, 2-, and 3-D, using ray-by-ray neutrino transport, approximate general relativity, and detailed neutrino and nuclear physics. We discuss some early results from our current series of exploding 2D simulations and our work to perform computationally tractable simulations in 3D using the "Yin-Yang" grid.

  8. Chimera distribution amplitudes for the pion and the longitudinally polarized $\\rho$-meson

    Stefanis, N G

    2016-01-01

    Using QCD sum rules with nonlocal condensates, we show that the distribution amplitude of the longitudinally polarized $\\rho$-meson may have a shorttailed platykurtic profile in close analogy to our recently proposed platykurtic distribution amplitude for the pion. Such a chimera distribution de facto amalgamates the broad unimodal profile of the distribution amplitude, obtained with a Dyson-Schwinger equations-based computational scheme, with the suppressed tails characterizing the bimodal distribution amplitudes derived from QCD sum rules with nonlocal condensates. We argue that pattern formation, emerging from the collective synchronization of coupled oscillators, can provide a single theoretical scaffolding to study unimodal and bimodal distribution amplitudes of light mesons without recourse to particular computational schemes and the reasons for them.

  9. Approximate Waveforms for Extreme-Mass-Ratio Inspirals: The Chimera Scheme

    Sopuerta, Carlos F

    2012-01-01

    We describe a new kludge scheme to model the dynamics of generic extreme-mass-ratio inspirals (EMRIs; stellar compact objects spiraling into a spinning supermassive black hole) and their gravitational-wave emission. The Chimera scheme is a hybrid method that combines tools from different approximation techniques in General Relativity: (i) A multipolar, post-Minkowskian expansion for the far-zone metric perturbation (the gravitational waveforms) and for the local prescription of the self-force; (ii) a post-Newtonian expansion for the computation of the multipole moments in terms of the trajectories; and (iii) a BH perturbation theory expansion when treating the trajectories as a sequence of self-adjusting Kerr geodesics. The EMRI trajectory is made out of Kerr geodesic fragments joined via the method of osculating elements as dictated by the multipolar post-Minkowskian radiation-reaction prescription. We implemented the proper coordinate mapping between Boyer-Lindquist coordinates, associated with the Kerr geo...

  10. Chimera distribution amplitudes for the pion and the longitudinally polarized ρ-meson

    Stefanis, N. G.; Pimikov, A. V.

    2016-01-01

    Using QCD sum rules with nonlocal condensates, we show that the distribution amplitude of the longitudinally polarized ρ-meson may have a shorttailed platykurtic profile in close analogy to our recently proposed platykurtic distribution amplitude for the pion. Such a chimera distribution de facto amalgamates the broad unimodal profile of the distribution amplitude, obtained with a Dyson-Schwinger equations-based computational scheme, with the suppressed tails characterizing the bimodal distribution amplitudes derived from QCD sum rules with nonlocal condensates. We argue that pattern formation, emerging from the collective synchronization of coupled oscillators, can provide a single theoretical scaffolding to study unimodal and bimodal distribution amplitudes of light mesons without recourse to particular computational schemes and the reasons for them.

  11. Development of a large scale Chimera grid system for the Space Shuttle Launch Vehicle

    Pearce, Daniel G.; Stanley, Scott A.; Martin, Fred W., Jr.; Gomez, Ray J.; Le Beau, Gerald J.; Buning, Pieter G.; Chan, William M.; Chiu, Ing-Tsau; Wulf, Armin; Akdag, Vedat

    1993-01-01

    The application of CFD techniques to large problems has dictated the need for large team efforts. This paper offers an opportunity to examine the motivations, goals, needs, problems, as well as the methods, tools, and constraints that defined NASA's development of a 111 grid/16 million point grid system model for the Space Shuttle Launch Vehicle. The Chimera approach used for domain decomposition encouraged separation of the complex geometry into several major components each of which was modeled by an autonomous team. ICEM-CFD, a CAD based grid generation package, simplified the geometry and grid topology definition by provoding mature CAD tools and patch independent meshing. The resulting grid system has, on average, a four inch resolution along the surface.

  12. Mechanisms of Core-Collapse Supernovae & Simulation Results from the CHIMERA Code

    Bruenn, S W; Hix, W R; Blondin, J M; Marronetti, P; Messer, O E B; Dirk, C J; Yoshida, S

    2010-01-01

    Unraveling the mechanism for core-collapse supernova explosions is an outstanding computational challenge and the problem remains essentially unsolved despite more than four decades of effort. However, much progress in realistic modeling has occurred recently through the availability of multi-teraflop machines and the increasing sophistication of supernova codes. These improvements have led to some key insights which may clarify the picture in the not too distant future. Here we briefly review the current status of the three explosion mechanisms (acoustic, MHD, and neutrino heating) that are currently under active investigation, concentrating on the neutrino heating mechanism as the one most likely responsible for producing explosions from progenitors in the mass range ~10 to ~25 solar masses. We then briefly describe the CHIMERA code, a supernova code we have developed to simulate core-collapse supernovae in 1, 2, and 3 spatial dimensions. We finally describe the results of an ongoing suite of 2D simulations...

  13. Novel type of chimera spiral waves arising from decoupling of a diffusible component

    Tang, Xiaodong; Yang, Tao; Liu, Yang; Zhao, Yuemin; Gao, Qingyu, E-mail: epstein@brandeis.edu, E-mail: gaoqy@cumt.edu.cn [College of Chemical Engineering, China University of Mining and Technology, Xuzhou 221008 (China); Epstein, Irving R., E-mail: epstein@brandeis.edu, E-mail: gaoqy@cumt.edu.cn [Department of Chemistry and Volen Center for Complex Systems, MS 015, Brandeis University, Waltham, Massachusetts 02454-9110 (United States)

    2014-07-14

    Spiral waves composed of coherent traveling waves surrounding a core containing stochastically distributed stationary areas are found in numerical simulations of a three-variable reaction-diffusion system with one diffusible species. In the spiral core, diffusion of this component (w) mediates transitions between dynamic states of the subsystem formed by the other two components, whose dynamics is more rapid than that of w. Diffusive coupling between adjacent sites can be “on” or “off” depending on the subsystem state. The incoherent structures in the spiral core are produced by this decoupling of the slow diffusive component from the fast non-diffusing subsystem. The phase diagram reveals that the region of incoherent behavior in chimera spirals grows drastically, leading to modulation and breakup of the spirals, in the transition zones between 1{sup n-1} and 1{sup n} local mixed-mode oscillations.

  14. Two- and three-dimensional simulations of core-collapse supernovae with CHIMERA

    Lentz, Eric J [ORNL; Bruenn, S. W. [Florida Atlantic University, Boca Raton; Harris, James A [ORNL; Chertkow, Merek A [ORNL; Hix, William Raphael [ORNL; Mezzacappa, Anthony [ORNL; Messer, Bronson [ORNL; Blondin, J. M. [North Carolina State University; Marronetti, Pedro [Florida Atlantic University, Boca Raton; Mauney, Christopher M [ORNL; Yakunin, Konstantin [Florida Atlantic University, Boca Raton

    2012-01-01

    Ascertaining the core-collapse supernova mechanism is a complex, and yet unsolved, problem dependent on the interaction of general relativity, hydrodynamics, neutrino transport, neutrino-matter interactions, and nuclear equations of state and reaction kinetics. Ab initio modeling of core-collapse supernovae and their nucleosynthetic outcomes requires care in the coupling and approximations of the physical components. We have built our multi-physics CHIMERA code for supernova modeling in 1-, 2-, and 3-D, using ray-by-ray neutrino transport, approximate general relativity, and detailed neutrino and nuclear physics. We discuss some early results from our current series of exploding 2D simulations and our work to perform computationally tractable simulations in 3D using the ``Yin--Yang'' grid.

  15. 2D and 3D Core-Collapse Supernovae Simulation Results Obtained with the CHIMERA Code

    Bruenn, S W; Hix, W R; Blondin, J M; Marronetti, P; Messer, O E B; Dirk, C J; Yoshida, S

    2010-01-01

    Much progress in realistic modeling of core-collapse supernovae has occurred recently through the availability of multi-teraflop machines and the increasing sophistication of supernova codes. These improvements are enabling simulations with enough realism that the explosion mechanism, long a mystery, may soon be delineated. We briefly describe the CHIMERA code, a supernova code we have developed to simulate core-collapse supernovae in 1, 2, and 3 spatial dimensions. We then describe the results of an ongoing suite of 2D simulations initiated from a 12, 15, 20, and 25 solar mass progenitor. These have all exhibited explosions and are currently in the expanding phase with the shock at between 5,000 and 20,000 km. We also briefly describe an ongoing simulation in 3 spatial dimensions initiated from the 15 solar mass progenitor.

  16. The determination of lymphoid cell chimerism using peripheral blood lymphocytes from murine bone marrow chimeras

    A simple, rapid and accurate method was devised for determining lymphoid cell chimerism in bone marrow-reconstituted mice. Chimeras were produced by reconstituting lethally irradiated mice with semi-allogeneic bone marrow cells. Lymphocytes from the peripheral blood of individual chimeric mice were purified by sedimentation in dextran solution and differential flotation in Ficoll-Hypaque gradients. From 250-500 μl of blood, 1-7 x 105 cells were routinely obtained. The extent of chimerism was determined serologically by using peripheral blood lymphocytes as target cells in a dye exclusion microcytotoxicity assay. Using this new technique, approximately 80% of the reconstituted mice were found to be repopulated with lymphocytes of the donor type. (Auth.)

  17. CHIMERA II - A real-time multiprocessing environment for sensor-based robot control

    Stewart, David B.; Schmitz, Donald E.; Khosla, Pradeep K.

    1989-01-01

    A multiprocessing environment for a wide variety of sensor-based robot system, providing the flexibility, performance, and UNIX-compatible interface needed for fast development of real-time code is addressed. The requirements imposed on the design of a programming environment for sensor-based robotic control is outlined. The details of the current hardware configuration are presented, along with the details of the CHIMERA II software. Emphasis is placed on the kernel, low-level interboard communication, user interface, extended file system, user-definable and dynamically selectable real-time schedulers, remote process synchronization, and generalized interprocess communication. A possible implementation of a hierarchical control model, the NASA/NBS standard reference model for telerobot control system is demonstrated.

  18. Adaptive differentiation of H-2- and Igh-restricted B lymphocyte in tetraparental bone marrow chimera

    Immunization of BALB/c mice with MOPC-104E myeloma protein induced idiotype-specific enhancing B cells that acted on anti-dextran antibody producing B cells. The enhancing cells have the surface phenotype of B cells. With the use of several H-2 or Igh congenic mice, it was found that the cooperation among B cells was controlled by both the major histocompatibility complex (MHC) and Igh. The capability to generate enhancing B cell activity was analyzed by using tetraparental bone marrow chimeras. (C57BL/6 X BALB/c)F1 mice, for example, were lethally irradiated and were reconstituted with C57BL/6 and BALB/c bone marrow cells. Nine to 12 wk after the reconstitution, the chimeras were immunized with the myeloma protein and were tested for their enhancing B cell activity. After the removal of C57BL/6 origin cells by treatment with anti-H-2b + complement, residual cells exhibited enhancing B cell activity on BALB.B, as well as BALB/c antidextran antibody response. This indicates that the generation of H-2-restricted, idiotype-specific enhancing B cell activity differentiated adaptively so as to recognize foreign MHC as self under chimeric conditions. On the other hand, splenic B cells treated with anti-H-2d + complement did not enhance the responses of BALB/c or BALB.B. Even in a chimeric environment, the B cells of C57BL/6 origin could not obtain the ability to generate enhancing B cell activity upon immunization of the idiotype. The results described here, taken in conjunction with our previous studies, suggest that the Ig heavy chain gene(s) predominantly control the Igh restriction properties of enhancing B cells, and the capability of MHC recognition by B cells is selected under chimeric conditions

  19. Chimera States in Earthquake Sequencing: Preliminary Results from Global Seismic Records

    Vasudevan, Kris; Cavers, Michael S.

    2015-04-01

    Earthquakes are occurrences resulting from significant stress-field alterations among faults. In general, spatio-temporal stress-field fluctuations are complex. They evolve continuously. We propose that they are akin to the dynamics of the collective behaviour of weakly-coupled non-linear "oscillators". Here, an oscillation refers to a fault-system reaching a threshold value for an earthquake occurrence at a given time and then, falling into a quiescence period during which the stress-build-up reoccurs in a prescribed manner. The duration of the quiescence period varies from one fault system to the other, depending on the forces behind it. Since mapping of global stress-field fluctuations in real time at all scales is an impossible task, we consider an earthquake zone as a proxy for a collection of weakly-coupled oscillators the dynamics of which would befit the ubiquitous Kuramoto model. In the present work, we apply the Kuramoto model to understand the non-linear dynamics on a directed graph of a sequence of global earthquakes. For directed graphs with certain properties, the Kuramoto model yields either synchronization or asynchronization. Inclusion of non-local effects evokes the occurrence of chimera states or the co-existence of synchronous and asynchronous behaviour of oscillators. In this presentation, we show how we build the model for directed graphs derived from global seismicity data. Then, we present conditions under which chimera states could occur and subsequently, point out the role of Kuramoto model in understanding the evolution of synchronous and asynchronous regions. We interpret our results with the spectral properties of directed graphs.

  20. Cross-reactivity of hypervariable region 1 chimera of hepatitis C virus

    Bing-Shui Xiu; Shi-Gan Ling; Xiao-Guo Song; He-Qiu Zhang; Kun Chen; Cui-Xia Zhu

    2003-01-01

    AIM: To analyze the amino acid sequences of hypervariable region 1 (HVR1) of HCV isolates in China and to construct a combinatorial chimeric HVR1 protein having a very broad high cross-reactivity. METHODS: All of the published HVR1 sequences from China were collected and processed with a computer program.Several representative HVR1's sequences were formulated based on a consensus profile and homology within certain subdivision. A few reported HVR1 mimotope sequences were also included for a broader representation. All of them were cloned and expressed in E.coli. The cross-reactivity of the purified recombinant HVR1 antigens was tested by ELISA with a panel of sera from HCV infected patients in China.Some of them were further ligated together to form a combinatorial HVR1 chimera. RESULTS: Altogether 12 HVR1s were selected and expressed in E. coli and purified to homogeneity. All of these purified antigens showed some cross-reactivity with sera in a 27 HCV positive panel. Recombinant HVR1s of No. 1, 2, 4, and 8# showing broad cross-reactivities and complementarity with each other, were selected for the ligation elements. The chimera containing these 4 HVR1s was highly expressed in E. coli. The purified chimeric antigen could react not only with all the HCV antibody positive sera in the panel but also with 90/91 sera of HCV -infected patients. CONCLUSION: The chimeric antigen was shown to have a broad cross-reactivity. It may be helpful for solving the problem caused by high variability of HCV, and in the efforts for a novel vaccine against the virus.

  1. Analysis of binding domain and function of chimeric opioid receptors to ohmefentanyl stereoisomers1%嵌合μ/κ阿片受体与羟甲芬太尼异构体结合部位和功能分析

    周德和; 池志强; 冯亚平; 谌立伟; 徐学军

    2001-01-01

    AIM: To investigate specific domains in μ opioid receptors that accounted for selective binding of three stereoisomers of ohmefentanyl (Ohm9204, Ohm9202, and Ohm9203) and study the function of chimera Ⅱ. METHODS: Rat μ and κ opioid receptors (RMOR, RKOR) and four μ/κ chimeric receptors (chimeras) Ⅰ , Ⅱ, Ⅲ, and Ⅳ were transiently expressed in COS-1 cells. The binding ability and binding domain of receptor to ligands were determined by radioactive ligand and receptor binding experiments. Through measuring cellular cAMP levels, we studied the function of chimera Ⅱ in mediating signal transduction. RESULTS: Binding affinities of four chimeric receptors were similar to wild type opioid receptors (RMOR and RKOR). The binding affinities of Ohm9204 and Ohm9202 to chimera Ⅱ were similar to that of RMOR. The binding affinities of Ohm9203 to all six receptors were low. U50488 possessed high binding affinity to chimera Ⅰ, however dynorphie A( 1 -9) had some binding affinity to chimera Ⅱ that was similar to RKOR, which indicated the domains of RKOR accounting for selectively binding to peptide ligand dynorphie A(1- 9) and nonpeptide ligand U50488 were different. The efficacy of Ohm9204 and Ohm9203 on inhibiting forskolin-stimulated cAMP accumulation in cells transfected with chimera Ⅱ was similar to that in cells transfected with RMOR. CONCLUSION: Replacing 194- 268 residues of RMOR with 185 - 262 residues of RKOR does not influence the ability of μ opioid receptor to bind Ohm9204 and Ohm9202 and the receptor mediated inhibition of cellular cAMP level.%目的:研究嵌合μ/κ阿片受体与羟甲芬太尼异构体 的结合部位及chimeraⅡ的功能.方法:在COS-1 细胞中瞬时表达大鼠μ、κ阿片受体(RMOR、 RKOR)以及四种嵌合μ/κ阿片受体chimera Ⅰ、Ⅱ、 Ⅲ、Ⅳ.用放射性受体结合实验进行受体活性的测 定和结合区域的分析.通过测定胞内cAMP的水 平,研究了chimeraⅡ介导

  2. Chimeric RXFP1 and RXFP2 receptors highlight the similar mechanism of activation utilizing their N-terminal low density lipoprotein class A modules

    Shoni eBruell

    2013-11-01

    Full Text Available Relaxin family peptide (RXFP receptors 1 and 2 are unique G-protein coupled receptors in that they contain an N-terminal low density lipoprotein type A (LDLa module which is necessary for receptor activation. The current hypothesis suggests that upon ligand binding the LDLa module interacts with the transmembrane (TM domain of a homodimer partner receptor to induce the active receptor conformations. We recently demonstrated that three residues in the N-terminus of the RXFP1 LDLa module are potentially involved in hydrophobic interactions with the receptor to drive activation. RXFP2 shares two out of three of the residues implicated, suggesting that the two LDLa modules could be interchanged without adversely affecting activity. However, in 2007 it was shown that a chimera consisting of the RXFP1 receptor with its LDLa swapped for that of RXFP2 did not signal. We noticed this construct also contained the RXFP2 region linking the LDLa to the leucine-rich repeats. We therefore constructed chimeric RXFP1 and RXFP2 receptors with their LDLa modules swapped immediately C-terminally to the final cysteine residue of the module, retaining the native linker. In addition, we exchanged the TM domains of the chimeras to explore if matching the LDLa module with the TM domain of its native receptor altered activity. All of the chimeras were expressed at the surface of HEK293T cells with ligand binding profiles similar to the wild-type receptors. Importantly, as predicted, ligand binding was able to induce cAMP based signalling. Chimeras of RXFP1 with the LDLa of RXFP2 demonstrated reduced H2 relaxin potency with the pairing of the RXFP2 TM with the RXFP2 LDLa necessary for full ligand efficacy. In contrast the ligand mediated potencies and efficacies on the RXFP2 chimeras were similar suggesting the RXFP1 LDLa module has similar efficacy on the RXFP2 TM domain. Our studies demonstrate the LDLa modules of RXFP1 and RXFP2 modulate receptor activation via a

  3. Chimeric RXFP1 and RXFP2 Receptors Highlight the Similar Mechanism of Activation Utilizing Their N-Terminal Low-Density Lipoprotein Class A Modules.

    Bruell, Shoni; Kong, Roy C K; Petrie, Emma J; Hoare, Brad; Wade, John D; Scott, Daniel J; Gooley, Paul R; Bathgate, Ross A D

    2013-01-01

    Relaxin family peptide (RXFP) receptors 1 and 2 are unique G-protein coupled receptors in that they contain an N-terminal low-density lipoprotein type A (LDLa) module which is necessary for receptor activation. The current hypothesis suggests that upon ligand binding the LDLa module interacts with the transmembrane (TM) domain of a homodimer partner receptor to induce the active receptor conformations. We recently demonstrated that three residues in the N-terminus of the RXFP1 LDLa module are potentially involved in hydrophobic interactions with the receptor to drive activation. RXFP2 shares two out of three of the residues implicated, suggesting that the two LDLa modules could be interchanged without adversely affecting activity. However, in 2007 it was shown that a chimera consisting of the RXFP1 receptor with its LDLa swapped for that of RXFP2 did not signal. We noticed this construct also contained the RXFP2 region linking the LDLa to the leucine-rich repeats. We therefore constructed chimeric RXFP1 and RXFP2 receptors with their LDLa modules swapped immediately C-terminally to the final cysteine residue of the module, retaining the native linker. In addition, we exchanged the TM domains of the chimeras to explore if matching the LDLa module with the TM domain of its native receptor altered activity. All of the chimeras were expressed at the surface of HEK293T cells with ligand binding profiles similar to the wild-type receptors. Importantly, as predicted, ligand binding was able to induce cAMP-based signaling. Chimeras of RXFP1 with the LDLa of RXFP2 demonstrated reduced H2 relaxin potency with the pairing of the RXFP2 TM with the RXFP2 LDLa necessary for full ligand efficacy. In contrast the ligand-mediated potencies and efficacies on the RXFP2 chimeras were similar suggesting the RXFP1 LDLa module has similar efficacy on the RXFP2 TM domain. Our studies demonstrate the LDLa modules of RXFP1 and RXFP2 modulate receptor activation via a similar mechanism. PMID

  4. Restricted antibody formation to sheep erythrocytes of allogeneic bone marrow chimeras histoincompatible at the K end of the H-2 complex

    Employing a new method for allogeneic bone marrow transplantation, irradiation chimeras constructed from various combinations of marrow cells from B10 H-2 recombinant mice and AKR recipients were prepared. Though these chimeras had well-developed populations of T and B cells, they showed strikingly different patterns of responses in the primary antibody formation to sheep erythrocytes (SRBC), a T dependent antigen. These are (a) AKR mice treated with C57BL/10 cells, [B10 leads to AKR] fully H-2 incompatible, and AKR mice treated with B10.A (5R) cells, [5R leads to AKR] I-J,E compatible chimeras that were almost completely unresponsive to SRBC; (b) AKR mice treated with B10.BR cells [BR leads to AKR] fully H-2 compatible, and AKR mice treated with B10 AKM cells, [AKM leads to AKR] chimeras where donor and recipient differed only at H-2D, showed the same number of plaque-forming cells (PFC) as B10 control mice; (c) AKR mice treated with B10.A cells, [B10 leads to AKR] chimeras, where donor and recipient were matched at H-2K-I-E region, showed about one-half the number of PFC as the control mice. From these results we conclude that in allogeneic bone marrow chimeras primary antibody response to T-dependent antigen, such as SRBC, is generated when at least the K end of the H-2 complex is compatible between donor and recipient

  5. Functional clonal deletion versus suppressor cell-induced transplantation tolerance in chimeras prepared with a short course of total-lymphoid irradiation

    Allogeneic bone marrow (BM) chimeras induced by infusion of BM cells into recipients conditioned with total lymphoid irradiation (TLI) were shown to develop humoral and cell-mediated tolerance to host and donor-type alloantigens by a number of in vitro and in vivo assays. Spleen cells of tolerant chimeras exhibited suppressive activity of mixed lymphocyte reaction (MLR). MLR suppression was not abrogated by depletion of Lyt-2 cells, and neither could Lyt-2-positive cells sorted from the spleens of tolerant chimeras suppress MLR or attenuate graft-versus-host reactivity in vivo. Likewise, specifically unresponsive spleen cells obtained from chimeras could not be induced to respond in MLR against tolerizing host-type cells following depletion of Lyt-2 or passage through a nylon-wool column. Tolerance of chimera spleen cells to host alloantigens, best documented by permanent survival of donor-type skin allografts, could be adoptively transferred into syngeneic recipients treated by heavy irradiation but not into untreated or mildly irradiated recipients. Adoptive transfer of tolerance seemed to be associated with experimental conditions favoring engraftment of tolerant cells rather than suppression of host reactivity. We speculate that although host and/or donor-derived suppressor cells may be operating in reducing the pool of specific alloreactive clones by blocking cell proliferation in response to allogeneic challenge, the final outcome in tolerant chimeras is actual or functional deletion of alloreactive clones

  6. Construction of serial deletants and chimeras of multi-kringle containing molecules and primary analysis of their functions

    宫锋; 董春娜; 张咏; 章杨培; 吴祖泽; 贺福初

    1999-01-01

    In comparison of amino acid sequences of 4 kringles of both macrophage stimulating protein (MSP) and hepatocyte growth factor (HGF), consensus motif sequence was determined. According to this consensus sequence, a pair of universal primers were designed. In combination with specific upstream or downstream primer of MSP or HGF respectively, serial fragments containing variant number of kringle (from 1 to 4) can be obtained by once PCR. By ligating the C terminal and N terminal fragments with different combination, serial deletants and chimeras of MSP and HGF were constructed. Sequence analysis showed that the degeneracy for universal primers and the sequences of those constructed deletants and chimeras are desired. Biological assay of these deletants revealed that wild type MSP can inhibit the growth of some tumor cell lines and that kringle 1 of MSP is essential for function as that of HGF.

  7. Early dominance of irradiated host cells in the responder profiles of thymocytes from P → F1 radiation chimeras

    The number of cells in the thymus of radiation (1000 rad) chimeras increases approximately 10-fold between 7 and 14 days after reconstitution with bone marrow. At least 50% of the cells in thymus on day 14 are of host origin and respond to virus presented in the context of both H-2/sup k/ and H-2/sup b/ when primed in irradiated, virus-infected (b x k)F1 recipients. Strong CTL responses can be generated from thymocytes of donor origin on day 21. All evidence of a significant host thymocyte component has disappeared by day 28. The responsiveness of 14-day thymocytes is not abrogated by pretreatment of the mice used to make the chimeras with anti-thymocyte serum or by using doses of irradiation as high as 1200 rads to eliminate host components

  8. Dominance and persistence of donor marrow in long-lived allogeneic radiation chimeras obtained with unmanipulated bone marrow

    Allogeneic, H-2-incompatible irradiation chimeras (H-2sup(d) → H-2sup(b)) constructed with normal, unmanipulated bone marrow and with marrow-derived factors live long and do not manifest a GvH disease. Their response to primary immunization is deficient but their alloreactivity is normal. This chimeric allotolerance cannot be passively transferred from chimeric donors to normal irradiated recipients. Passive transfer of both donor- or recipient-type immuno-competent T-cells into the chimeric mice does not lead to syngeneic reconstitution, rejection of the engrafted marrow or GvH disease, and the mice maintain permanently their chimerism. This new model demonstrates that chimerism is not eradicable in long-lived chimeras reconstituted with unmanipulated bone marrow, and that the bone marrow itself plays a dominant role in maintenance of chimerism. (Auth.)

  9. Stromal cells in long-term murine bone marrow culture: FACS studies and origin of stromal cells in radiation chimeras

    Adherent layers from hematopoietically active long-term bone marrow cultures (LTBMC), incubated with fluorescent beads, were analyzed for autofluorescence and phagocytic ability, using a fluorescence-activated cell sorter (FACS). Four groups of cells were separated from the adherent layers, including a group of large polygonal fibroblastoid stromal cells. Long-term chimeras were made by lethal irradiation of CBA/Ca (CBA) and C57Bl6/J (B6) mice and repopulation with phosphoglycerate kinase (PGK-1) alloenzyme-congenic bone marrow cells. Hematopoietically active LTBMC were established from such chimeras, and donor and host contributions of FACS-sorted adherent-layer cells were measured. While macrophages and other hematopoietic cells were of donor origin, the fibroblastoid stromal cells were mainly or entirely host derived

  10. Recombinant peptide replicates immunogenicity of synthetic linear peptide chimera for use as pre-erythrocytic stage malaria vaccine

    Silva-Flannery, Luciana M.; Cabrera-Mora, Monica; Jiang, Jianlin; Moreno, Alberto

    2008-01-01

    Synthetic linear peptide chimeras (LPCscys+) show promise as delivery platforms for malaria subunit vaccines. Maximal immune response to LPCscys+ in rodent malaria models depends upon formation of cross-linkages to generate homopolymers, presenting challenges for vaccine production. To replicate the immunogenicity of LPCscys+ using a recombinant approach, we designed a recombinant LPC (rLPC) based on Plasmodium yoelii circumsporozoite protein-specific sequences of 208 amino acids consisting o...

  11. 先天性嵌合体的形成与临床%Formation and clinical research of congenital chimera

    王琳凯; 张阮章; 王沙燕

    2014-01-01

    A chimera is produced by the fusion of two or more different zygotes in a single embryo.The chimerism has been rarely reported in humans.It is usually discovered because a discrepancy is observed in blood typing or sex chromosome complement.So far,several types of chimera have been discovered.However,the underlying mechanisms are poorly understood.In this article,the previous literatures which involved chimerism are reviewed,and the types of chimera,formation mechanisms,detected methods,and diagnostic strategies are summarized.We hope it is helpful to the research of chimera.%嵌合体是指同一个体中同时存在两个或多个不同细胞系的现象,在人类中比较罕见,一般是由于观察到血型或者性染色体异常才发现此种现象.目前,已陆续发现了多种类型的嵌合体,对其临床与实验室的研究取得了初步进展,但对于嵌合体的认识,特别是对其形成机制了解得尚不充分.该文中,回顾了以往文献对先天性嵌合体案例的报道及相关研究,并在其基础上总结了嵌合体的类型、形成机制、检测方法及诊断策略,以期进一步促进嵌合体的相关研究.

  12. Purification and characterization of Yersinia enterocolitica and Yersinia pestis LcrV–cholera toxin A2/B chimeras

    Tinker, Juliette K.; Chadwick T Davis; Arlian, Britni M.

    2010-01-01

    Yersinia pestis is a virulent human pathogen and potential biological weapon. Despite a long history of research on this organism, there is no licensed vaccine to protect against pneumonic forms of Y. pestis disease. In the present study, plasmids were constructed to express cholera toxin A2/B chimeric molecules containing the LcrV protective antigen from Y. enterocolitica and Y. pestis. These chimeras were expressed and purified to high yields from the supernatant of transformed E. coli. Wes...

  13. Co-targeting EGFR and survivin with a bivalent aptamer-dual siRNA chimera effectively suppresses prostate cancer.

    Liu, Hong Yan; Yu, Xiaolin; Liu, Haitao; Wu, Daqing; She, Jin-Xiong

    2016-01-01

    Current targeted therapies using small kinase inhibitors and antibodies have limited efficacy in treating prostate cancer (PCa), a leading cause of cancer death in American men. We have developed a novel strategy by engineering an RNA-based aptamer-siRNA chimera, in which a bivalent aptamer specifically binds prostate-specific membrane antigen (PSMA) via an antibody-like structure to promote siRNA internalization in PCa cells, and two siRNAs specific to EGFR and survivin are fused between two aptamers. The chimera is able to inhibit EGFR and survivin simultaneously and induce apoptosis effectively in vitro and in vivo. In the C4-2 PCa xenograft model, the treatment with the chimera significantly suppresses tumor growth and angiogenesis. The inhibition of angiogenesis is mediated by an EGFR-HIF1α-VEGF-dependent mechanism. Our results support that the bivalent aptamer-driven delivery of two siRNAs could be a new combination therapeutic strategy to effectively inhibit multiple and conventionally "undruggable" targets. PMID:27456457

  14. The ethics of killing human/great-ape chimeras for their organs: a reply to Shaw et al.

    Palacios-González, César

    2016-06-01

    The aim of this paper is to critically examine David Shaw, Wybo Dondorp, and Guido de Wert's arguments in favour of the procurement of human organs from human/nonhuman-primate chimeras, specifically from great-ape/human chimeras. My main claim is that their arguments fail and are in need of substantial revision. To prove this I first introduce the topic, and then reconstruct Shaw et al.'s position and arguments. Next, I show that Shaw et al.: (1) failed to properly apply the subsidiarity and proportionality principles; (2) neglected species overlapping cases in their ethical assessment; (3) ignored the ethics literature on borderline persons; and (4) misunderstood McMahan's two-tiered moral theory. These mistakes render an important part of their conclusions either false or problematic to the point that they would no longer endorse them. Finally I will briefly mention a possible multipolar solution to the human organ shortage problem that would reduce the need for chimeras' organs. PMID:26294174

  15. A Navier-Strokes Chimera Code on the Connection Machine CM-5: Design and Performance

    Jespersen, Dennis C.; Levit, Creon; Kwak, Dochan (Technical Monitor)

    1994-01-01

    We have implemented a three-dimensional compressible Navier-Stokes code on the Connection Machine CM-5. The code is set up for implicit time-stepping on single or multiple structured grids. For multiple grids and geometrically complex problems, we follow the 'chimera' approach, where flow data on one zone is interpolated onto another in the region of overlap. We will describe our design philosophy and give some timing results for the current code. A parallel machine like the CM-5 is well-suited for finite-difference methods on structured grids. The regular pattern of connections of a structured mesh maps well onto the architecture of the machine. So the first design choice, finite differences on a structured mesh, is natural. We use centered differences in space, with added artificial dissipation terms. When numerically solving the Navier-Stokes equations, there are liable to be some mesh cells near a solid body that are small in at least one direction. This mesh cell geometry can impose a very severe CFL (Courant-Friedrichs-Lewy) condition on the time step for explicit time-stepping methods. Thus, though explicit time-stepping is well-suited to the architecture of the machine, we have adopted implicit time-stepping. We have further taken the approximate factorization approach. This creates the need to solve large banded linear systems and creates the first possible barrier to an efficient algorithm. To overcome this first possible barrier we have considered two options. The first is just to solve the banded linear systems with data spread over the whole machine, using whatever fast method is available. This option is adequate for solving scalar tridiagonal systems, but for scalar pentadiagonal or block tridiagonal systems it is somewhat slower than desired. The second option is to 'transpose' the flow and geometry variables as part of the time-stepping process: Start with x-lines of data in-processor. Form explicit terms in x, then transpose so y-lines of data are

  16. Growth of transplantable melanoma and leukaemia and prevention of virus-induced leukaemia in long lived radiation chimeras constructed with unmanipulated bone marrow

    Haemopoietic radiation chimeras across the H-2 barrier (BALB/c → C57B1/6; H-2sup(d) → H-2sup(b) chimeras and vice versa) have been studied for their capacity to suppress the growth, or to reject, transplantable B16 melanotic melanoma and radiation leukaemia virus-induced, transplantable leukaemia. Also, radiation leukaemia virus (RadLV) obtained from the thymus of leukaemic C57B1/6 mice was injected i.p. into established chimeras (H-2sup(d) → H-2sup(b)). As expected, long lived, graft versus host disease free allogeneic chimeras constructed with intact bone marrow were unable to reject the tumours both when recipients were BALB/c → C57B1/6 or C57B1/6 → BALB/c chimeras. However, inoculation of a large number of immunocompetent cells from normal BALB/c mice into BALB/c → C57B1/6 chimeras failed to promote a rejection of the tumours. On the contrary, the same amount of syngeneic (BALB/c) immunocompetent cells prevented growth of melanoma when transferred into athymic nude BALB/c mice, while the tumour grew unimpaired in untreated athymic nude BALB/c mice. The same type of H-2sup(d) → H-2sup(b) chimeras displayed complete resistance to inoculation of leukaemogenic H-2sup(b) restricted RadLV while all H-2sup(b) → H-2sup(b), syngeneically reconstituted mice developed disseminated leukaemia. (author)

  17. Human-animal chimeras: ethical issues about farming chimeric animals bearing human organs.

    Bourret, Rodolphe; Martinez, Eric; Vialla, François; Giquel, Chloé; Thonnat-Marin, Aurélie; De Vos, John

    2016-01-01

    Recent advances in stem cells and gene engineering have paved the way for the generation of interspecies chimeras, such as animals bearing an organ from another species. The production of a rat pancreas by a mouse has demonstrated the feasibility of this approach. The next step will be the generation of larger chimeric animals, such as pigs bearing human organs. Because of the dramatic organ shortage for transplantation, the medical needs for such a transgressive practice are indisputable. However, there are serious technical barriers and complex ethical issues that must be discussed and solved before producing human organs in animals. The main ethical issues are the risks of consciousness and of human features in the chimeric animal due to a too high contribution of human cells to the brain, in the first case, or for instance to limbs, in the second. Another critical point concerns the production of human gametes by such chimeric animals. These worst-case scenarios are obviously unacceptable and must be strictly monitored by careful risk assessment, and, if necessary, technically prevented. The public must be associated with this ethical debate. Scientists and physicians have a critical role in explaining the medical needs, the advantages and limits of this potential medical procedure, and the ethical boundaries that must not be trespassed. If these prerequisites are met, acceptance of such a new, borderline medical procedure may prevail, as happened before for in-vitro fertilization or preimplantation genetic diagnosis. PMID:27356872

  18. All together now: Analogies between chimera state collapses and epileptic seizures

    Andrzejak, Ralph G.; Rummel, Christian; Mormann, Florian; Schindler, Kaspar

    2016-03-01

    Conceptually and structurally simple mathematical models of coupled oscillator networks can show a rich variety of complex dynamics, providing fundamental insights into many real-world phenomena. A recent and not yet fully understood example is the collapse of coexisting synchronous and asynchronous oscillations into a globally synchronous motion found in networks of identical oscillators. Here we show that this sudden collapse is promoted by a further decrease of synchronization, rather than by critically high synchronization. This strikingly counterintuitive mechanism can be found also in nature, as we demonstrate on epileptic seizures in humans. Analyzing spatiotemporal correlation profiles derived from intracranial electroencephalographic recordings (EEG) of seizures in epilepsy patients, we found a pronounced decrease of correlation at the seizure onsets. Applying our findings in a closed-loop control scheme to models of coupled oscillators in chimera states, we succeed in both provoking and preventing outbreaks of global synchronization. Our findings not only advance the understanding of networks of coupled dynamics but can open new ways to control them, thus offering a vast range of potential new applications.

  19. Numerical Simulation of Rotor-aerodynamic Surface Interaction in Hover Using Moving Chimera Grid

    LI Yibo; MA Dongli

    2012-01-01

    Three-dimensional unsteady Navier-Stokes equations are numerically solved to simulate the aerodynamic interaction of rotor,canard and horizontal tail in hover based on moving chimera grid.The variations of unsteady aerodynamic forces and moments of the canard and horizontal tail with respect to the rotor azimuth are analyzed with the deflection angle set at 0° and 50°,respectively.The pressure map of aerodynamic surfaces and velocity vector distribution of flow field are investigated to get better understanding of the unsteady aerodynamic interaction.The result shows that the canard and horizontal tail present different characteristics under the downwash of the rotor.The canard produces much vertical force loss with low amplitude fluctuation.Contrarily,the horizontal tail,which is within the flow field induced by the down wash of the rotor,produces only less vertical force loss,but the amplitudes of the lift and pitching moment are larger,implying that a potential deflection angle scheme in hover is 50° for the canard and 0° for the horizontal tail.

  20. Scalar-Quark Systems and Chimera Hadrons in SU(3)_c Lattice QCD

    Iida, H; Takahashi, T T

    2007-01-01

    Light scalar-quarks \\phi (colored scalar particles or idealized diquarks) and their color-singlet hadronic states are studied with quenched SU(3)_c lattice QCD in terms of mass generation in strong interaction without chiral symmetry breaking. We investigate ``scalar-quark mesons'' \\phi^\\dagger \\phi and ``scalar-quark baryons'' \\phi\\phi\\phi which are the bound states of scalar-quarks \\phi. We also investigate the bound states of scalar-quarks \\phi and quarks \\psi, i.e., \\phi^\\dagger \\psi, \\psi\\psi\\phi and \\phi\\phi\\psi, which we name ``chimera hadrons''. All the new-type hadrons including \\phi are found to have a large mass even for zero bare scalar-quark mass m_\\phi=0 at a^{-1}\\simeq 1GeV. We find that the constituent scalar-quark and quark picture is satisfied for all the new-type hadrons. Namely, the mass of the new-type hadron composed of m \\phi's and n \\psi's, M_{{m}\\phi+{n}\\psi}, satisfies M_{{m}\\phi+{n}\\psi}\\simeq {m} M_\\phi +{n} M_\\psi, where M_\\phi and M_\\psi are the constituent scalar-quark and quark...

  1. Macrophage function in murine allogeneic bone marrow radiation chimeras in the early phase after transplantation

    We tested several of the functions of macrophages (M phi) in the early phase after allogeneic bone marrow transfer to get information about this important aspect of the nonspecific immune system in the T-cell-deficient recipient. On days 3-5 after transfer, the number of M phi was reduced in the spleen, liver, lungs, and peritoneal cavity (Pe). The phagocytosis of sheep red blood cells (SRBC) by these M phi was normal or even enhanced, as in the case of Pe-M phi. Already on days 8-12 after transfer, the number of M phi in spleen and liver exceeded that of controls, whereas the number was still reduced in lungs and Pe. We examined their ability to kill P815 tumor cells, to produce tumor necrosis factor-alpha (TNF alpha), to phagocytose SRBC, to produce reactive oxygen intermediates (ROI) in vitro and to kill Listeria monocytogenes in vivo. Most functions were normal and often even enhanced, depending on the organ origin, but the ability of Pe-M phi to produce ROI was reduced. Proliferative response to macrophage colony-stimulating factor (M-CSF) and killing of YAC-1 tumor cells revealed a high frequency of macrophage precursor cells in the spleen and liver and a high natural killer (NK) activity in the liver. Altogether, enhanced nonspecific immune function, especially preactivated M phi, may enable chimeras to survive attacks by opportunistic pathogens

  2. Aerodynamic study of sounding rocket flows using Chimera and patched multiblock meshes

    João Alves de Oliveira Neto

    2011-01-01

    Full Text Available Aerodynamic flow simulations over a typical sounding rocket are presented in this paper. The work is inserted in the effort of developing computational tools necessary to simulate aerodynamic flows over configurations of interest for Instituto de Aeronáutica e Espaço of Departamento de Ciência e Tecnologia Aeroespacial. Sounding rocket configurations usually require fairly large fins and, quite frequently, have more than one set of fins. In order to be able to handle such configurations, the present paper presents a novel methodology which combines both Chimera and patched multiblock grids in the discretization of the computational domain. The flows of interest are modeled using the 3-D Euler equations and the work describes the details of discretization procedure, which uses a finite difference approach for structure, body-conforming, multiblock grids. The method is used to calculate the aerodynamics of a sounding rocket vehicle. The results indicate that the present approach can be a powerful aerodynamic analysis and design tool.

  3. Tsh receptor

    Frauman, Albert

    2013-01-01

    The TSH receptor is a member of the G protein-coupled receptor(GPCR)family. It is one of the glycoprotein hormone receptors, which also includes the FSH and LH/CG receptors. The TSH receptor mediates the action of the pituitary-derived glycoprotein, TSH (thyroid stimulating hormone, thyrotropin or thyrotrophin). TSH binds to the TSH receptor which is located on thyroid follicular cells (but is also expressed in extrathyroidal sites). Glycosylation of the TSH receptor occurs, as does cleavage ...

  4. Effective suppression of C5a-induced proinflammatory response using anti-human C5a repebody.

    Hwang, Da-Eun; Choi, Jung-Min; Yang, Chul-Su; Lee, Joong-Jae; Heu, Woosung; Jo, Eun-Kyeong; Kim, Hak-Sung

    2016-09-01

    The strongest anaphylatoxin, C5a, plays a critical role in the proinflammatory responses, causing the pathogenesis of a number of inflammatory diseases including sepsis, asthma, and rheumatoid arthritis. Inhibitors of C5a thus have great potential as therapeutics for various inflammatory disorders. Herein, we present the development of a high-affinity repebody against human C5a (hC5a), which effectively suppresses the proinflammatory response. A repebody scaffold composed of leucine-rich repeat (LRR) modules was previously developed as an alternative protein scaffold. A repebody specifically binding to hC5a was selected through a phage display, and its affinity was increased up to 5 nM using modular engineering. The repebody was shown to effectively inhibit the production of C5a-induced proinflammatory cytokines by human monocytes. To obtain insight into a mode of action by the repebody, we determined its crystal structure in complex with hC5a. A structural analysis revealed that the repebody binds to the D1 and D3 regions of hC5a, overlapping several epitope residues with the hC5a receptor (hC5aR). It is thus likely that the repebody suppresses the hC5a-mediated immune response in monocytes by blocking the binding of hC5a to its receptor. The anti-hC5a repebody can be developed as a potential therapeutic for C5a-involved inflammatory diseases. PMID:27416759

  5. Ligand-dependent interactions of the Ah receptor with coactivators in a mammalian two-hybrid assay

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a high affinity ligand for the aryl hydrocarbon receptor (AhR). In this study, we investigated structure-dependent differences in activation of the AhR by a series of halogenated aromatic hydrocarbons. TCDD, 1,2,3,7,8-pentachlorodibenzo-p-dioxin (PeCDD), 2,3,7,8-tetrachlorodibenzofuran (TCDF), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), and 3,3',4,4',5-pentachlorobiphenyl (PCB126) induced CYP1A1-dependent activities in HEK293 human embryonic kidney, Panc1 pancreatic cancer, and Hepa1c1c7 mouse hepatoma cell lines. There was a structure-dependent difference in the efficacy of TCDF and PCB126 in HEK293 and Panc1 cells since induced CYP1A1 mRNA levels were lower than observed for the other congeners. A mammalian two-hybrid assay in cells transfected with GAL4-coactivator and AhR-VP16 chimeras was used to investigate structure-dependent interactions of these chimeras in Panc1, HEK293, and Hepa1c1c7 cells. The reporter construct pGAL4-luc contains five tandem GAL4 response elements linked to the luciferase gene and the GAL4-coactivator chimeras express several coactivators including steroid receptor coactivator 1 (SRC-1), SRC-2 and SRC-3, the mediator coactivator TRAP220, coactivator associated arginine methyl transferase 1 (CARM-1), and peroxisome proliferator-activated receptor γ coactivator 1 (PGC-1). Results of the mammalian two-hybrid studies clearly demonstrate that activation of pGAL4-luc in cells transfected with VP-AhR and GAL4-coactivator chimeras is dependent on the structure of the HAH congener, cell context, and coactivator, suggesting that the prototypical HAH congeners used in this study exhibit selective AhR modulator activity

  6. Dynamics of Somatic Cell-Lineage Competition in Chimeras of Hydractinia symbiolongicarpus (Cnidaria: Hydrozoa) Dinámica de competencia entre líneas celulares somáticas en quimeras de Hydractinia symbiolongicarpus (Cnidaria: Hydrozoa)

    RYAN S SCHWARZ; Cadavid, Luis F.

    2007-01-01

    Sessile colonial invertebrates often fuse with conspecifics to form chimeras. Chimerism represents an unequivocal instance of withinindividual selection where genetically different celllineages compete for representation in the somatic and gametic pools. We analyzed temporal and spatial variations in somatic celllineage composition of laboratoryestablished chimeras of the hydroid Hydractinia symbiolongicarpus (Cnidaria: Hydrozoa). Using three clones with different allotyp...

  7. Study of structure function correlation of chemokine receptor CXCR4

    ZHENG Hong; Stephen C PEIPER; ZHU Xi-hua

    2002-01-01

    Objective: To explore the correlation between structure domains and functions of chemokine receptor CXCR4. Methods: After the establishment of wild type chemokine receptor CXCR4 and CXCR2 expressing cell lines, 5 CXCR4/CXCR2 chimeras, 2 CXCR4 mutants were stably expressed on CHO cell line.Binding activities of all variants with the ligand, recombinant human SDF-1β, signal transduction ability after stimulation and their function as coreceptor for HIV-1 were studied with ligand-binding assay, Cytosensor/microphysiometry and cell-cell reporter gene fusion assay. Results: Among all 7 changed CXCR4 receptors, 3 chimeras (2444a, 4442, 4122), and 1 mutant (CXCR4-Tr) bond with SDF-1β in varying degrees, of which only 2444a totally and CXCR4-Tr partially maintain signaling. All changed receptors except for 4222 could act as coreceptors for HIV-1(LAI) in varying degrees. Conclusion: Several structure domains of CXCR4 are involved in the binding with SDF-1β, among which, N-terminal extracellular domain has high affinity of binding with SDF-1β, and the 3rd extracellular loop contributes to the binding, too. Although the C-terminal intracellular domain has no association with the maintenance of the overall structure of the receptor and ligand binding capability, the signaling is decreased when this domain is truncated. For CXCR4 signaling, not only is the conserved motif DRY box needed, but also the characterized conformation of the whole molecule must be formed when activation is required. There are some overlaps between SDF-1β binding domains and coreceptor function domains in molecular structure of CXCR4.

  8. Chimera proteins with affinity for membranes and microtubule tips polarize in the membrane of fission yeast cells.

    Recouvreux, Pierre; Sokolowski, Thomas R; Grammoustianou, Aristea; Ten Wolde, Pieter Rein; Dogterom, Marileen

    2016-02-16

    Cell polarity refers to a functional spatial organization of proteins that is crucial for the control of essential cellular processes such as growth and division. To establish polarity, cells rely on elaborate regulation networks that control the distribution of proteins at the cell membrane. In fission yeast cells, a microtubule-dependent network has been identified that polarizes the distribution of signaling proteins that restricts growth to cell ends and targets the cytokinetic machinery to the middle of the cell. Although many molecular components have been shown to play a role in this network, it remains unknown which molecular functionalities are minimally required to establish a polarized protein distribution in this system. Here we show that a membrane-binding protein fragment, which distributes homogeneously in wild-type fission yeast cells, can be made to concentrate at cell ends by attaching it to a cytoplasmic microtubule end-binding protein. This concentration results in a polarized pattern of chimera proteins with a spatial extension that is very reminiscent of natural polarity patterns in fission yeast. However, chimera levels fluctuate in response to microtubule dynamics, and disruption of microtubules leads to disappearance of the pattern. Numerical simulations confirm that the combined functionality of membrane anchoring and microtubule tip affinity is in principle sufficient to create polarized patterns. Our chimera protein may thus represent a simple molecular functionality that is able to polarize the membrane, onto which additional layers of molecular complexity may be built to provide the temporal robustness that is typical of natural polarity patterns. PMID:26831106

  9. Newcastle disease virus chimeras expressing the Hemagglutinin- Neuraminidase protein of mesogenic strain exhibits an enhanced anti-hepatoma efficacy.

    He, Jinjiao; Pan, Ziye; Tian, Guiyou; Liu, Xin; Liu, Yunye; Guo, Xiaochen; An, Ying; Song, Liying; Wu, Hongsong; Cao, Hongwei; Yu, Dan; Che, Ruixiang; Xu, Pengfei; Rasoul, Lubna M; Li, Deshan; Yin, Jiechao

    2016-08-01

    Newcastle disease virus (NDV) is an intrinsically tumor-specific virus, many researchers have reported that lentogenic NDV is a safe and effective agent for human cancer therapy. It had been demonstrated that the amino acid sequence of the fusion protein cleavage site is a major factor in the pathogenicity and anti-tumor efficacy of rNDV. However, the role of Hemagglutinin-Neuraminidase (HN) gene that contributes to virulence and anti-tumor efficacy remains undefined. To assess the role of HN gene in virus pathogenicity and anti-tumor efficacy, a reverse genetic system was developed using the lentogenic NDV Clone30 strain to provide backbone for gene exchange. Chimeric virus (rClone30-Anh(HN)) created by exchange of the HN gene of lentogenic strain Clone30 with HN gene of mesogenic strain produce no significant changes in virus pathogenicity as assessed by conducting the mean death time (MDT) and intracerebral pathogenicity index (ICPI) assays. In vitro, infection with chimeras could induce the formation of syncytium relative significantly in HepG2 cells. Furthermore, chimeras was shown to induce the cell apoptosis via MTT and Annexin V-PI assays, reduce mitochondrial membrane potential and increase the mRNA transcription level of caspase 3. In vivo, ICR mice carrying tumor of hepatoma H22 cells were treated via intratumoral injection of chimeric virus. The treatment of chimera shows an obvious suppression in tumor volume. These results suggest that it could be an ideal approach to enhance the antitumor ability of Newcastle disease virus and highlighted the potential therapeutic application of rClone30-Anh(HN) as a viral vector to deliver foreign genes for treatment of cancers. PMID:27164362

  10. CONSTRUCTION OF HU-PBL/SCID CHIMERAS AND DEVELOPMENT OF EBV-RELATED LYMPHOMAS

    Run-liang Gan; Ke Lan; Zhi-hua Yin; Li-jiang Wang; Ying Song; Kai-tai Yao

    2005-01-01

    Objective To construct hu-PBL/SCID chimeras and to investigate the development of lymphoma and oncogenicity of the Epstein-Barr virus (EBV).Mtehods Human peripheral blood lymphocytes (PBLs) were isolated from healthy adult donors and transplanted intraperitoneally into severe combined immunodeficient (SCID) mice. Mice with hu-PBL engraftment from healthy EBV seronegative donors were injected intraperitoneally with EBV-containing supematant from suspension culture of B95-8 cell line (active infection), whereas mice receiving lymphocytes from healthy EBV seropositive donors were not re-infected with B95-8 derived EBV (latent infection). Pathological examination and molecular analysis were performed on experimental animals and induced neoplasms.Results In the early stage of this experiment, 12 mice died of acute graft-versus-host disease, mortality was 34.3%(12/35 mice) with an average life span of 17.5 days. In 19 survival hu-PBL/SCID chimeric recipients from 12 healthy donors,tumor incidence was 84.2% (16/19 mice). The average survival time of tumor-bearing mice was 65.5 days. EBV-related neoplasms in SCID mice were nodular tumors with aggressive and fatal features. Histological morphology of tumors exhibited diffuse large cell lymphomas. Immunohistochemistry revealed that LCA (CD45) and L26 (CD20) were positive, but both PS1 (CD3) and UCHL-1 (CD45RO) were negative, and EBV products ZEBRA, LMP1, and EBNA2 were expressed in a small number of tumor cells. EB virus particles were seen in the nuclei of some tumor cells by electron microscopy, and EBV DNA could be amplified in the tumor tissues by PCR. In situ hybridization indicated that the nuclei of tumor cells contained human-specific Alu sequence.Conclusions EBV-induced tumors were human B-cell malignant lymphomas. We obtained direct causative evidence dealing with EBV-associated tumor deriving from normal human cells.

  11. Characterization and dynamics of aggresome formation by a cytosolic GFP-chimera.

    García-Mata, R; Bebök, Z; Sorscher, E J; Sztul, E S

    1999-09-20

    Formation of a novel structure, the aggresome, has been proposed to represent a general cellular response to the presence of misfolded proteins (Johnston, J.A., C.L. Ward, and R.R. Kopito. 1998. J. Cell Biol. 143:1883-1898; Wigley, W.C., R.P. Fabunmi, M.G. Lee, C.R. Marino, S. Muallem, G.N. DeMartino, and P.J. Thomas. 1999. J. Cell Biol. 145:481-490). To test the generality of this finding and characterize aspects of aggresome composition and its formation, we investigated the effects of overexpressing a cytosolic protein chimera (GFP-250) in cells. Overexpression of GFP-250 caused formation of aggresomes and was paralleled by the redistribution of the intermediate filament protein vimentin as well as by the recruitment of the proteasome, and the Hsp70 and the chaperonin systems of chaperones. Interestingly, GFP-250 within the aggresome appeared not to be ubiquitinated. In vivo time-lapse analysis of aggresome dynamics showed that small aggregates form within the periphery of the cell and travel on microtubules to the MTOC region where they remain as distinct but closely apposed particulate structures. Overexpression of p50/dynamitin, which causes the dissociation of the dynactin complex, significantly inhibited the formation of aggresomes, suggesting that the minus-end-directed motor activities of cytoplasmic dynein are required for aggresome formation. Perinuclear aggresomes interfered with correct Golgi localization and disrupted the normal astral distribution of microtubules. However, ER-to-Golgi protein transport occurred normally in aggresome containing cells. Our results suggest that aggresomes can be formed by soluble, nonubiquitinated proteins as well as by integral transmembrane ubiquitinated ones, supporting the hypothesis that aggresome formation might be a general cellular response to the presence of misfolded proteins. PMID:10491388

  12. A chimera grid scheme. [multiple overset body-conforming mesh system for finite difference adaptation to complex aircraft configurations

    Steger, J. L.; Dougherty, F. C.; Benek, J. A.

    1983-01-01

    A mesh system composed of multiple overset body-conforming grids is described for adapting finite-difference procedures to complex aircraft configurations. In this so-called 'chimera mesh,' a major grid is generated about a main component of the configuration and overset minor grids are used to resolve all other features. Methods for connecting overset multiple grids and modifications of flow-simulation algorithms are discussed. Computational tests in two dimensions indicate that the use of multiple overset grids can simplify the task of grid generation without an adverse effect on flow-field algorithms and computer code complexity.

  13. Particle identification method in the CsI(Tl) scintillator used for the CHIMERA 4 pi detector

    Alderighi, M; Basssini, R; Berceanu, I; Blicharska, J; Boiano, C; Borderie, B; Bougault, R; Bruno, M; Cali, C; Cardella, G; Cavallaro, S; D'Agostino, M; D'andrea, M; Dayras, R; De Filippo, E; Fichera, F; Geraci, E; Giustolisi, F; Grzeszczuk, A; Guardone, N; Guazzoni, P; Guinet, D; Iacono-Manno, M; Kowalski, S; La Guidara, E; Lanchais, A L; Lanzalone, G; Lanzanò, G; Le Neindre, N; Li, S; Maiolino, C; Majka, Z; Manfredi, G; Nicotra, D; Paduszynski, T; Pagano, A; Papa, M; Petrovici, C M; Piasecki, E; Pirrone, S; Politi, G; Pop, A; Porto, F; Rivet, M F; Rosato, E; Sacca, G; Sechi, G; Simion, V; Sperduto, M L; Steckmeyer, J C; Trifiró, A; Trimarchi, M; Urso, S; Vannini, G; Vigilante, M; Wilczynski, J; Wu, H; Xiao, Z; Zetta, L; Zipper, W

    2002-01-01

    The charged particle identification obtained by the analysis of signals coming from the CsI(Tl) detectors of the CHIMERA 4 pi heavy-ion detector is presented. A simple double-gate integration method, with the use of the cyclotron radiofrequency as reference time, results in low thresholds for isotopic particle identification. The dependence of the identification quality on the gate generation timing is discussed. Isotopic identification of light ions up to Beryllium is clearly seen. For the first time also the identification of Z=5 particles is observed. The identification of neutrons interacting with CsI(Tl) by (n,alpha) and (n,gamma) reactions is also discussed.

  14. Role of 5-HT5A receptors in activation of astroglia in the spinal dorsal horn in a rat model of neuropathic pain by vincristine%5-HT5A受体在长春新碱致神经病理性痛大鼠脊髓背角星形胶质细胞活化中的作用

    刘巍; 叶茂; 徐颖; 石远; 柏林

    2010-01-01

    目的 评价5-羟色胺5A受体(5-HT5AR)在长春新碱致神经病理性痛大鼠脊髓背角星形胶质细胞活化中的作用.方法 雄性成年SD大鼠40只,体重180~200 g,随机分为4组(n=10):对照组(C组)、神经病理性痛组(P组)、空载体腺病毒组(B组)和siRNA重组腺病毒载体组(S组).C组腹腔注射生理盐水1 ml;P组、B组和S组第1~5天和第8~12天每天定时腹腔注射0.1 mg/kg长春新碱建立大鼠神经病理性痛模型.腹腔给药结束第2天测定机械痛阈,然后P组、B组和S组分别鞘内注射人工脑脊液、空载体腺病毒和siRNA重组腺病毒载体25μl.鞘内给药后第7天测定机械痛阈,然后处死大鼠,取L4.5脊髓组织,测定脊髓背角5-HT5AR及胶原纤维酸性蛋白(GFAP)的表达.结果 与C组比较,P组、B组和S组各时点机械痛阈降低,脊髓背角5-HT5AR和GFAP的表达均上调(P<0.05);与P组比较,S组鞘内给药后第7天机械痛阈降低,脊髓背角5-HT5AR表达下调,GFAP表达上调(P<0.05),B组上述指标差异无统计学意义(P>0.05).结论 5-HT5AR参与了星形胶质细胞活化的抑制过程,从而减轻长春新碱致大鼠神经病理性痛.%Objective To evaluate the role of 5-HT5A receptors (5-HT5A R) in activation of astroglia in the spinal dorsal horn in a rat model of neuropathic pain induced by vincristine. Methods Forty adult male SD rats weighing 180-200 g were randomly divided into 4 groups ( n = 10 each): control group (group C);neuropathic pain group (group P);Ad-X-HK group (group B) and Ad-5-HT5A-siRNA group (group S). Neuropathic pain was induced by repeated intraperitoneal (IP) injection of vincristine 0.1 mg/kg according to the method described by Weng et al in group P, B and S. On the 2nd day after the last IP injection, the animals received artificial cerebrospinal fluid, Ad-X-HK and Ad-5-HT5A-siRNA 25 μl administered intrathecally (IT) in group P, B and S respectively. Paw withdrawal threshold to mechanical stimulus

  15. CHIMERA: a wide-field, multi-colour, high-speed photometer at the prime focus of the Hale telescope

    Harding, L. K.; Hallinan, G.; Milburn, J.; Gardner, P.; Konidaris, N.; Singh, N.; Shao, M.; Sandhu, J.; Kyne, G.; Schlichting, H. E.

    2016-04-01

    The Caltech HIgh-speed Multi-colour camERA (CHIMERA) is a new instrument that has been developed for use at the prime focus of the Hale 200-inch telescope. Simultaneous optical imaging in two bands is enabled by a dichroic beam splitter centred at 567 nm, with Sloan u' and g' bands available on the blue arm and Sloan r', i' and z_s bands available on the red arm. Additional narrow-band filters will also become available as required. An electron multiplying CCD (EMCCD) detector is employed for both optical channels, each capable of simultaneously delivering sub-electron effective read noise under multiplication gain and frame rates of up to 26 fps full frame (several 1000 fps windowed), over a fully corrected 5 × 5 arcmin field of view. CHIMERA was primarily developed to enable the characterization of the size distribution of sub-km Kuiper Belt Objects via stellar occultation, a science case that motivates the frame-rate, the simultaneous multi-colour imaging and the wide field of view of the instrument. In addition, it also has unique capability in the detection of faint near-Earth asteroids and will be used for the monitoring of short-duration transient and periodic sources, particularly those discovered by the intermediate Palomar Transient Factory (iPTF), and the upcoming Zwicky Transient Facility (ZTF).

  16. CHIMERA: a wide-field, multi-color, high-speed photometer at the prime focus of the Hale telescope

    Harding, Leon K; Milburn, Jennifer; Gardner, Paul; Konidaris, Nick; Singh, Navtej; Shao, Michael; Sandhu, Jagmit; Kyne, Gillian; Schlichting, Hilke E

    2016-01-01

    The Caltech HIgh-speed Multi-color camERA (CHIMERA) is a new instrument that has been developed for use at the prime focus of the Hale 200-inch telescope. Simultaneous optical imaging in two bands is enabled by a dichroic beam splitter centered at 567 nm, with Sloan u' and g' bands available on the blue arm and Sloan r', i' and z_s' bands available on the red arm. Additional narrow-band filters will also become available as required. An Electron Multiplying CCD (EMCCD) detector is employed for both optical channels, each capable of simultaneously delivering sub-electron effective read noise under multiplication gain and frame rates of up to 26 fps full frame (several 1000 fps windowed), over a fully corrected 5 x 5 arcmin field of view. CHIMERA was primarily developed to enable the characterization of the size distribution of sub-km Kuiper Belt Objects via stellar occultation, a science case that motivates the frame-rate, the simultaneous multi-color imaging and the wide field of view of the instrument. In ad...

  17. A chimera of green fluorescent protein with single chain variable fragment antibody against ginsenosides for fluorescence-linked immunosorbent assay.

    Sakamoto, Seiichi; Tanizaki, Yusuke; Pongkitwitoon, Benyakan; Tanaka, Hiroyuki; Morimoto, Satoshi

    2011-05-01

    A chimera of green fluorescent protein extracted from Aequorea coerulescens (AcGFP), a mutant that has been codon optimized for mammalian expression, with single-chain variable fragment (scFv) antibody against ginsenoside Re (GRe-scFv), named fluobody, has been successfully expressed in Escherichia coli (E. coli) to develop simple, speedy, and sensitive fluorescence-linked immunosorbent assay (FLISA). Two chimera proteins were constructed to contain GRe-scFv at the C-terminus of AcGFP (C-fluobody) and at the N-terminus of AcGFP (N-fluobody). These fluobodies were then purified by ion metal affinity chromatography and refolded by stepwise dialysis. The characterization of both fluobodies revealed that C-fluobody was found to be appropriate probe for FLISA as compare with N-fluobody. Furthermore, improvement of limit of detection (LOD) was observed in FLISA using C-fluobody (10 ng/mL) due to its strong fluorescence intensity of AcGFP compared with conventional enzyme-linked immunosorbent assay (ELISA) using parental monoclonal antibody against ginsenoside Re (G-Re), MAb-4G10 (100 ng/mL). Since some steps required in ELISA can be avoided in this present FLISA, speedy and sensitive immunoassay also could be performed using fluobody instead of monoclonal antibody and scFv. PMID:21277981

  18. T cell receptor zeta allows stable expression of receptors containing the CD3gamma leucine-based receptor-sorting motif

    Dietrich, J; Geisler, C

    1998-01-01

    that the leucine-based motif in these complexes was inactive. In contrast, the CD4/CD3gamma chimeras did not associate with TCRzeta, and the leucine-based motif in these chimeras was constitutively active resulting in a high spontaneous internalization rate and low expression of the chimeras at the cell surface...

  19. Bone marrow cells from allogeneic bone marrow chimeras inhibit the generation of cytotoxic lymphocyte responses against both donor and recipient cells

    When added to a mixed lymphocyte culture, bone marrow cells suppress the generation of CTL activity against H-2 Ag shared by the BM cells and the stimulator cells. These cells have been referred to as veto cells and are thought to play a role in maintaining self-tolerance. We analyzed the H-2 specificity of the suppression expressed by the veto cells from H-2 incompatible bone marrow chimeras, because lymphocytes of such chimeras had been shown to be tolerant to both donor and recipient Ag when tested by CTL responses. We found that the bone marrow cells of such chimeras which were featured by non-T and non-B cell characteristics inhibited the generation of CTL directed against either donor or recipient Ag, but not against third-party Ag. These observations suggest that in allogeneic chimeras the veto or veto-like cells alter the inhibitory specificity exhibited in the recipient microenvironment and indicate that these cells are directly involved in the induction and maintenance of self-tolerance

  20. Contrasting feature in the repopulation of host-type T cells in the spleens of F1----P and P----F1 radiation bone marrow chimeras

    The regeneration and persistence of host- and donor-derived T cells were examined in the thymus as well as the spleen of mouse radiation bone marrow chimeras of two semiallogeneic combinations (F1----P, P----F1) with different Thy-1 markers on T cells of donor and host origins. An unexpectedly large number of host-type T cells were recovered from the spleens of F1----P chimeras, amounting to as high as 45 and 25% of total T cells at 6 and 14 weeks after bone marrow transplantation (BMT), respectively. To the contrary, the residual host-type T cells in the spleens of P----F1 chimeras disappeared quickly, resulting in less than 0.1% of total T cells at 6 weeks after BMT. It was also revealed that the number of host-type T cells in the spleens of F1----P chimeras decreased in proportion to increase of radiation dose given to the recipients

  1. Insights into the Activity and Substrate Binding of Xylella fastidiosa Polygalacturonase by Modification of a Unique QMK Amino Acid Motif Using Protein Chimeras.

    Warren, Jeremy G; Lincoln, James E; Kirkpatrick, Bruce C

    2015-01-01

    Polygalacturonases (EC 3.2.1.15) catalyze the random hydrolysis of 1, 4-alpha-D-galactosiduronic linkages in pectate and other galacturonans. Xylella fastidiosa possesses a single polygalacturonase gene, pglA (PD1485), and X. fastidiosa mutants deficient in the production of polygalacturonase are non-pathogenic and show a compromised ability to systemically infect grapevines. These results suggested that grapevines expressing sufficient amounts of an inhibitor of X. fastidiosa polygalacturonase might be protected from disease. Previous work in our laboratory and others have tried without success to produce soluble active X. fastidiosa polygalacturonase for use in inhibition assays. In this study, we created two enzymatically active X. fastidiosa / A. vitis polygalacturonase chimeras, AX1A and AX2A to explore the functionality of X. fastidiosa polygalacturonase in vitro. The AX1A chimera was constructed to specifically test if recombinant chimeric protein, produced in Escherichia coli, is soluble and if the X. fastidiosa polygalacturonase catalytic amino acids are able to hydrolyze polygalacturonic acid. The AX2A chimera was constructed to evaluate the ability of a unique QMK motif of X. fastidiosa polygalacturonase, most polygalacturonases have a R(I/L)K motif, to bind to and allow the hydrolysis of polygalacturonic acid. Furthermore, the AX2A chimera was also used to explore what effect modification of the QMK motif of X. fastidiosa polygalacturonase to a conserved RIK motif has on enzymatic activity. These experiments showed that both the AX1A and AX2A polygalacturonase chimeras were soluble and able to hydrolyze the polygalacturonic acid substrate. Additionally, the modification of the QMK motif to the conserved RIK motif eliminated hydrolytic activity, suggesting that the QMK motif is important for the activity of X. fastidiosa polygalacturonase. This result suggests X. fastidiosa polygalacturonase may preferentially hydrolyze a different pectic substrate or

  2. Chimera states in a globally coupled discontinuous map lattices%一个全局耦合不连续映像格子中的奇异态

    程兴超; 杨科利; 屈世显

    2014-01-01

    文章研究了一类由既不可逆又不连续映像构成的全局耦合映像格子系统中的奇异态行为,计算了系统的同步序参量和空间振幅变化图。结果表明,在某些特定的参数区间内,耦合映像格子系统会出现奇异态或团簇态,并且敏感地依赖于耦合强度的选择。上述丰富的动力学现象是由于单映像中不连续、不可逆性以及空间耦合相互作用的结果。通过数值模拟找到了奇异态或团簇态出现的特定参数区域。%The chimera states and cluster chimera states in a globally coupled both discontinuous-and-non-invertible-map lattices are studied using the order parameters and spatial-time-amplitude patterns. The result show that chimera states and cluster chimera states are sensitive depends on the choice of the coupling strength, and they are induced by the interaction between the discontinuity and the non-invertibility in coupled system. We also discuss the conditions for the chimera states existing in this system.

  3. Chimeric antigen receptor T cell therapy: 25years in the making.

    Gill, Saar; Maus, Marcela V; Porter, David L

    2016-05-01

    Chimeric antigen receptor (CAR) T cell therapy of cancer is generating enormous enthusiasm. Twenty-five years after the concept was first proposed, major advances in molecular biology, virology, and good manufacturing practices (GMP)-grade cell production have transformed antibody-T cell chimeras from a scientific curiosity to a fact of life for academic cellular immunotherapy researchers and, increasingly, for patients. In this review, we explain the preclinical concept, outline how it has been translated to the clinic, and draw lessons from the first years of CAR T cell therapy for the practicing clinician. PMID:26574053

  4. Influence of the hinge region and its adjacent domains on binding and signaling patterns of the thyrotropin and follitropin receptor.

    Schaarschmidt, Jörg; Huth, Sandra; Meier, René; Paschke, Ralf; Jaeschke, Holger

    2014-01-01

    Glycoprotein hormone receptors (GPHR) have a large extracellular domain (ECD) divided into the leucine rich repeat (LRR) domain for binding of the glycoprotein hormones and the hinge region (HinR), which connects the LRR domain with the transmembrane domain (TMD). Understanding of the activation mechanism of GPHRs is hindered by the unknown interaction of the ECD with the TMD and the structural changes upon ligand binding responsible for receptor activation. Recently, our group showed that the HinR of the thyrotropin receptor (TSHR) can be replaced by those of the follitropin (FSHR) and lutropin receptor (LHCGR) without effects on surface expression and hTSH signaling. However, differences in binding characteristics for bovine TSH at the various HinRs were obvious. To gain further insights into the interplay between LRR domain, HinR and TMD we generated chimeras between the TSHR and FSHR. Our results obtained by the determination of cell surface expression, ligand binding and G protein activation confirm the similar characteristics of GPHR HinRs but they also demonstrate an involvement of the HinR in ligand selectivity indicated by the observed promiscuity of some chimeras. While the TSHR HinR contributes to specific binding of TSH and its variants, no such contribution is observed for FSH and its analog TR4401 at the HinR of the FSHR. Furthermore, the charge distribution at the poorly characterized LRR domain/HinR transition affected ligand binding and signaling even though this area is not in direct contact with the ligand. In addition our results also demonstrate the importance of the TMD/HinR interface. Especially the combination of the TSHR HinR with the FSHR-TMD resulted in a loss of cell surface expression of the respective chimeras. In conclusion, the HinRs of GPHRs do not only share similar characteristics but also behave as ligand specific structural and functional entities. PMID:25340405

  5. Influence of the hinge region and its adjacent domains on binding and signaling patterns of the thyrotropin and follitropin receptor.

    Jörg Schaarschmidt

    Full Text Available Glycoprotein hormone receptors (GPHR have a large extracellular domain (ECD divided into the leucine rich repeat (LRR domain for binding of the glycoprotein hormones and the hinge region (HinR, which connects the LRR domain with the transmembrane domain (TMD. Understanding of the activation mechanism of GPHRs is hindered by the unknown interaction of the ECD with the TMD and the structural changes upon ligand binding responsible for receptor activation. Recently, our group showed that the HinR of the thyrotropin receptor (TSHR can be replaced by those of the follitropin (FSHR and lutropin receptor (LHCGR without effects on surface expression and hTSH signaling. However, differences in binding characteristics for bovine TSH at the various HinRs were obvious. To gain further insights into the interplay between LRR domain, HinR and TMD we generated chimeras between the TSHR and FSHR. Our results obtained by the determination of cell surface expression, ligand binding and G protein activation confirm the similar characteristics of GPHR HinRs but they also demonstrate an involvement of the HinR in ligand selectivity indicated by the observed promiscuity of some chimeras. While the TSHR HinR contributes to specific binding of TSH and its variants, no such contribution is observed for FSH and its analog TR4401 at the HinR of the FSHR. Furthermore, the charge distribution at the poorly characterized LRR domain/HinR transition affected ligand binding and signaling even though this area is not in direct contact with the ligand. In addition our results also demonstrate the importance of the TMD/HinR interface. Especially the combination of the TSHR HinR with the FSHR-TMD resulted in a loss of cell surface expression of the respective chimeras. In conclusion, the HinRs of GPHRs do not only share similar characteristics but also behave as ligand specific structural and functional entities.

  6. RNA Interference in Mammalia Cells by RNA-3’-PNA Chimeras

    Anna Messere

    2008-03-01

    Full Text Available The discovery of siRNAs as the mediators of RNA interference has led to an increasing interest in their therapeutic applications. Chemical modifications are introduced into siRNAs to optimize the potency, the stability and the pharmacokinetic properties in vivo. Here, we synthesize and test the effects of RNA-3’-PNA chimeras on siRNA functioning and stability. We demonstrate that the chemical modifications are compatible with the siRNA machinery, because all the PNA-modified siRNAs can efficiently mediate specific gene silencing in mammalian cells. Furthermore, we find that the modification on the sense strand of siRNA results in an increased persistence of the activity, whereas modification on both strands results in enhanced nuclease resistance in serum.

  7. Restriction specificity of virus-specific cytotoxic T cells from thymectomised irradiated bone marrow chimeras reconstituted with thymus grafts

    Adult-thymectomised lethally irradiated mice A that were reconstituted with T-cell-depleted bone marrow cells of (A X B)F1 origin plus fetal thymus grafts of (B X C)F1 origin generated virus-specific T cells restricted to B alone; adult-thymectomised and lethally irradiated (A X B)F1 mice that were reconstituted with T-cell depleted bone marrow cells of (A X B)F1 origin plus fetal thymus grafts of A and of B origin generated virus-specific T cells restricted to A or to B. These results do not reveal obvious suppressive influences of host or stem-cell origin that might have explained results obtained with various irradiated bone marrow or thymus chimeras, they indicate that the thymus' influence on maturing T cells is one of the limiting steps in the selection of T cells' restriction specificities. (Auth.)

  8. Simulation of unsteady flows through stator and rotor blades of a gas turbine using the Chimera method

    Nakamura, S.; Scott, J. N.

    1993-01-01

    A two-dimensional model to solve compressible Navier-Stokes equations for the flow through stator and rotor blades of a turbine is developed. The flow domains for the stator and rotor blades are coupled by the Chimera method that makes grid generation easy and enhances accuracy because the area of the grid that have high turning of grid lines or high skewness can be eliminated from the computational domain after the grids are generated. The results of flow computations show various important features of unsteady flows including the acoustic waves interacting with boundary layers, Karman vortex shedding from the trailing edge of the stator blades, pulsating incoming flow to a rotor blade from passing stator blades, and flow separation from both suction and pressure sides of the rotor blades.

  9. Irregular macroscopic dynamics due to chimera states in small-world networks of pulse-coupled oscillators

    We study the collective dynamics of excitatory integrate-and-fire-like oscillators interacting via δ-pulses on a small-world network. The oscillators are endowed with refractory periods and time delays. For weak coupling strengths, the network self-organizes into synchronous and asynchronous regions. Such chimera states allow for two separate routes to synchrony/asynchrony. In addition to the loss of stability of either synchronous or asynchronous regions mediated by long-ranged connections, regions may grow or shrink mediated by the lattice structure. The interplay between these behaviors leads to controlled total sizes of asynchronous regions or to an alternation of synchronization and desynchronization phenomena with irregular macroscopic observables. (paper)

  10. Genetic resistance in experimental autoimmune encephalomyelitis. I. Analysis of the mechanism of LeR resistance using radiation chimeras

    Experimental autoimmune encephalomyelitis (EAE) is a cell-mediated autoimmune disease of the central nervous system that has been extensively studied in the rat. The Lewis rat is highly susceptible to the induction of EAE, while the Lewis resistant (LeR) rat is known to be resistant. In this paper, we demonstrate that the LeR rat, which was derived from the Lewis strain by inbreeding of fully resistant animals, is histocompatible with the Lewis strain. Radiation chimeras, a tool for distinguishing between immunologic and nonimmunologic resistance mechanisms, were utilized to analyze the cellular mechanisms involved in genetic resistance to EAE. By transplanting bone marrow cells from LeR rats into irradiated Lewis recipients, Lewis rats were rendered resistant to EAE induction. Likewise, transplanting Lewis bone marrow cells into irradiated LeR recipients rendered LeR rats susceptible. Mixed lymphoid cell chimeras using bone marrow, spleen, and thymus cells in Lewis recipient rats revealed individual lymphoid cell types and cell interactions that significantly affected the incidence and severity of EAE. Our results suggest that LeR resistance is mediated by hematopoietic/immune cells, and that cells located in the spleen appear to play a critical role in the resistance/susceptibility to EAE induction. Depletion of splenic adherent cells did not change the patterns of EAE resistance. In vivo cell mixing studies suggested the presence of a suppressor cell population in the LeR spleen preparations which exerted an inhibitory effect on Lewis autoimmune responses. Thus, the mechanism of LeR resistance appears to be different from that in other EAE-resistant animals

  11. Persistence of the irradiated host component in thymocyte populations from bone marrow radiation chimeras infected with lymphocytic choriomeningitis virus

    The thymus of chimeras made using T cell-depleted donor bone marrow from Thy1.1+ mice and 950 rad Thy 1.2+ recipients is dominated initially by cells expressing the Thy 1.2+ phenotype of the irradiated host. The thymocyte population recovered at 2 weeks after reconstitution comprises 80% Thy 1.2+ cells (host), the remainder being Thy 1.1+ (donor). This situation is normally reversed within a further week, with the host Ty 1.2+ (donor). This situation is normally reversed within a further week, with the host Thy 1.2+ thymocytes being present at a frequency of less than 5% from Week 4. Infection with lymphocytic choriomeningitis virus (LCMV) at 1 week after reconstitution with bone marrow causes a profound and persistent drop in the total number of thymocytes. The decline is equivalent for all categories of donor-derived thymocytes defined by two-color flow microfluorometric analysis for CD4 and CD8. However, there is a partial compensation by the retention of cells originating from the Thy 1.2+ host, which constitute 30-40% of the total thymocyte pool as late as 8 weeks after administration of bone marrow in the LCMV-infected chimeras. These radiation-resistant precursors give rise to CD4-8-, CD4-8+, CD4+8-, and CD4+8+ thymocytes, with the latter category being present at increased frequency. The potential skewing of the mature T cell repertoire as a consequence of persistent virus infection is discussed

  12. The proposed channel-enzyme transient receptor potential melastatin 2 does not possess ADP ribose hydrolase activity.

    Iordanov, Iordan; Mihályi, Csaba; Tóth, Balázs; Csanády, László

    2016-01-01

    Transient Receptor Potential Melastatin 2 (TRPM2) is a Ca(2+)-permeable cation channel essential for immunocyte activation, insulin secretion, and postischemic cell death. TRPM2 is activated by ADP ribose (ADPR) binding to its C-terminal cytosolic NUDT9-homology (NUDT9H) domain, homologous to the soluble mitochondrial ADPR pyrophosphatase (ADPRase) NUDT9. Reported ADPR hydrolysis classified TRPM2 as a channel-enzyme, but insolubility of isolated NUDT9H hampered further investigations. Here we developed a soluble NUDT9H model using chimeric proteins built from complementary polypeptide fragments of NUDT9H and NUDT9. When expressed in E.coli, chimeras containing up to ~90% NUDT9H sequence remained soluble and were affinity-purified. In ADPRase assays the conserved Nudix-box sequence of NUDT9 proved essential for activity (kcat~4-9s(-1)), that of NUDT9H did not support catalysis. Replacing NUDT9H in full-length TRPM2 with soluble chimeras retained ADPR-dependent channel gating (K1/2~1-5 μM), confirming functionality of chimeric domains. Thus, TRPM2 is not a 'chanzyme'. Chimeras provide convenient soluble NUDT9H models for structural/biochemical studies. PMID:27383051

  13. Fungal phosphate transporter serves as a receptor backbone for gibbon ape leukemia virus

    Pedersen, Lene; van Zeijl, Marja; Johann, Stephen V;

    1997-01-01

    Pit1, the receptor for gibbon ape leukemia virus (GALV), is proposed to be an integral membrane protein with five extracellular loops. Chimeras made between Pit1 homologs differing in permissivity for infection and between Pit1 and the related protein Pit2 have shown that the fourth extracellular...... loop plays a critical role in infection. However, further elucidation of the roles of the extracellular loops in infection is hampered by the high level of sequence similarity among these proteins. The sodium-dependent phosphate transporter, Pho-4, from the filamentous fungus Neurospora crassa is...... in a functional GALV receptor. Therefore, the presence of a Pit1 loop 4-specific sequence is sufficient to confer receptor function for the mammalian retrovirus GALV on the fungal phosphate transporter Pho-4...

  14. Importance of constitutive activity and arrestin-independent mechanisms for intracellular trafficking of the ghrelin receptor

    Holliday, Nicholas D; Holst, Birgitte; Rodionova, Elena A;

    2007-01-01

    . Furthermore the interaction between phosphorylated receptors and beta-arrestin adaptor proteins has been examined. Replacement of the FLAG-tagged GhrelinR C tail with the equivalent GPR39 domain (GhR-39 chimera) preserved G(q) signaling. However in contrast to the GhrelinR, GhR-39 receptors exhibited no basal...... and substantially decreased agonist-induced internalization in transiently transfected HEK293 cells. Internalized GhrelinR and GhR-39 were predominantly localized to recycling compartments, identified with transferrin and the monomeric G proteins Rab5 and Rab11. Both the inverse agonist [d-Arg(1), d...... embryonic fibroblasts. In contrast, agonist-stimulated GhrelinRs recruited the clathrin adaptor green fluorescent protein-tagged beta-arrestin2 to endosomes, coincident with increased receptor phosphorylation. Thus, GhrelinR internalization to recycling compartments depends on C-terminal motifs and...

  15. Molecular basis for high affinity and selectivity of peptide antagonist, Bantag-1, for the orphan BB3 receptor.

    Nakamura, Taichi; Ramos-Álvarez, Irene; Iordanskaia, Tatiana; Moreno, Paola; Mantey, Samuel A; Jensen, R T

    2016-09-01

    Bombesin-receptor-subtype-3 (BB3 receptor) is a G-protein-coupled-orphan-receptor classified in the mammalian Bombesin-family because of high homology to gastrin-releasing peptide (BB2 receptor)/neuromedin-B receptors (BB1 receptor). There is increased interest in BB3 receptor because studies primarily from knockout-mice suggest it plays roles in energy/glucose metabolism, insulin-secretion, as well as motility and tumor-growth. Investigations into its roles in physiological/pathophysiological processes are limited because of lack of selective ligands. Recently, a selective, peptide-antagonist, Bantag-1, was described. However, because BB3 receptor has low-affinity for all natural, Bn-related peptides, little is known of the molecular basis of its high-affinity/selectivity. This was systematically investigated in this study for Bantag-1 using a chimeric-approach making both Bantag-1 loss-/gain-of-affinity-chimeras, by exchanging extracellular (EC) domains of BB3/BB2 receptor, and using site-directed-mutagenesis. Receptors were transiently expressed and affinities determined by binding studies. Bantag-1 had >5000-fold selectivity for BB3 receptor over BB2/BB1 receptors and substitution of the first EC-domain (EC1) in loss-/gain-of affinity-chimeras greatly affected affinity. Mutagenesis of each amino acid difference in EC1 between BB3 receptor/BB2 receptor showed replacement of His(107) in BB3 receptor by Lys(107) (H107K-BB3 receptor-mutant) from BB2 receptor, decreased affinity 60-fold, and three replacements [H107K, E11D, G112R] decreased affinity 500-fold. Mutagenesis in EC1's surrounding transmembrane-regions (TMs) demonstrated TM2 differences were not important, but R127Q in TM3 alone decreased affinity 400-fold. Additional mutants in EC1/TM3 explored the molecular basis for these changes demonstrated in EC1, particularly important is the presence of aromatic-interactions by His(107), rather than hydrogen-bonding or charge-charge interactions, for determining

  16. Endocytosis of a functionally enhanced GFP-tagged transferrin receptor in CHO cells.

    Qi He

    Full Text Available The endocytosis of transferrin receptor (TfR has served as a model to study the receptor-targeted cargo delivery system for cancer therapy for many years. To accurately evaluate and optically measure this TfR targeting delivery in vitro, a CHO cell line with enhanced green fluorescent protein (EGFP-tagged human TfR was established. A chimera of the hTfR and EGFP was engineered by fusing EGFP to the amino terminus of hTfR. Data were provided to demonstrate that hTfR-EGFP chimera was predominantly localized on the plasma membrane with some intracellular fluorescent structures on CHO cells and the EGFP moiety did not affect the endocytosis property of hTfR. Receptor internalization occurred similarly to that of HepG2 cells expressing wild-type hTfR. The internalization percentage of this chimeric receptor was about 81 ± 3% of wild type. Time-dependent co-localization of hTfR-EGFP and PE-conjugated anti-hTfR mAb in living cells demonstrated the trafficking of mAb-receptor complexes through the endosomes followed by segregation of part of the mAb and receptor at the late stages of endocytosis. The CHO-hTfR cells preferentially took up anti-hTfR mAb conjugated nanoparticles. This CHO-hTfR cell line makes it feasible for accurate evaluation and visualization of intracellular trafficking of therapeutic agents conjugated with transferrin or Abs targeting the hTfRs.

  17. Loss of bone marrow adrenergic beta 1 and 2 receptors modifies transcriptional networks, reduces circulating inflammatory factors, and regulates blood pressure.

    Ahmari, Niousha; Schmidt, Jordan T; Krane, Gregory A; Malphurs, Wendi; Cunningham, Bruce E; Owen, Jennifer L; Martyniuk, Christopher J; Zubcevic, Jasenka

    2016-07-01

    Hypertension (HTN) is a prevalent condition with complex etiology and pathophysiology. Evidence exists of significant communication between the nervous system and the immune system (IS), and there appears to be a direct role for inflammatory bone marrow (BM) cells in the pathophysiology of hypertension. However, the molecular and neural mechanisms underlying this interaction have not been characterized. Here, we transplanted whole BM cells from the beta 1 and 2 adrenergic receptor (AdrB1(tm1Bkk)AdrB2(tm1Bkk)/J) knockout (KO) mice into near lethally irradiated C57BL/6J mice to generate a BM AdrB1.B2 KO chimera. This allowed us to evaluate the role of the BM beta 1 and beta 2 adrenergic receptors in mediating BM IS homeostasis and regulating blood pressure (BP) in an otherwise intact physiological setting. Fluorescence-activated cell sorting demonstrated that a decrease in systolic and mean BP in the AdrB1.B2 KO chimera is associated with a decrease in circulating inflammatory T cells, macrophage/monocytes, and neutrophils. Transcriptomics in the BM identified 7,419 differentially expressed transcripts between the C57 and AdrB1.B2 KO chimera. Pathway analysis revealed differentially expressed transcripts related to several cell processes in the BM of C57 compared with AdrB1.B2 KO chimera, including processes related to immunity (e.g., T-cell activation, T-cell recruitment, cytokine production, leukocyte migration and function), the cardiovascular system (e.g., blood vessel development, peripheral nerve blood flow), and the brain (e.g., central nervous system development, neurite development) among others. This study generates new insight into the molecular events that underlie the interaction between the sympathetic drive and IS in modulation of BP. PMID:27235450

  18. Bacterial membrane activity of a-peptide/b-peptoid chimeras: Influence of amino acid composition and chain length on the activity against different bacterial strains

    Hein-Kristensen, Line; Knapp, Kolja M; Franzyk, Henrik;

    2011-01-01

    BACKGROUND: Characterization and use of antimicrobial peptides (AMPs) requires that their mode of action is determined. The interaction of membrane-active peptides with their target is often established using model membranes, however, the actual permeabilization of live bacterial cells and...... permeabilization of the bacterial cell envelope, and the outer membrane may act as a barrier in Gram-negative bacteria. The tolerance of S. marcescens to chimeras may be due to differences in the composition of the lipopolysaccharide layer also responsible for its resistance to polymyxin B....... subsequent killing is usually not tested. In this report, six α-peptide/β-peptoid chimeras were examined for the effect of amino acid/peptoid substitutions and chain length on the membrane perturbation and subsequent killing of food-borne and clinical bacterial isolates. RESULTS: All six AMP analogues...

  19. Genes encoding chimeras of Neurospora crassa erg-3 and human TM7SF2 proteins fail to complement Neurospora and yeast sterol C-14 reductase mutants

    A Prakash; Durgadas P Kasbekar

    2002-03-01

    The human gene TM7SF2 encodes a polypeptide (SR-1) with high sequence similarity to sterol C-14 reductase, a key sterol biosynthetic enzyme in fungi, plants and mammals. In Neurospora and yeast this enzyme is encoded by the erg-3 and erg24 genes respectively. In an effort to demonstrate sterol C-14 reductase activity for SR-1 we constructed six recombinant genes coding for chimeras of the Neurospora erg-3 and SR-1 protein sequences and tested them for complementation of the Neurospora erg-3 mutant. To our surprise, all the chimeras failed to complement erg-3. A few of the chimeric proteins were also tested against the yeast erg24 mutant, but again there was no complementation. We discuss some reasons that might account for these unexpected findings.

  20. Mouse immature oocytes irradiated in vivo at 14-days of age and evaluated for transmitted effects using the aggregation embryo chimera assay

    A previous study using the mouse-preimplantation-embryo-chimera assay demonstrated a reproducible transmitted effect (proliferation disadvantage observed in early embryos) from females irradiated as 49-day-old adults using 0.15 Gy of gamma rays and then mated seven weeks later, i.e., embryos were from oocytes that were immature at time of irradiation. Because mouse immature oocytes are known to be much more radiosensitive to cell killing in juveniles than in adults, a follow-on study was performed here using 14-day-old juvenile mice. In contrast to adults, the exposure of juveniles to 0.15 Gy of gamma rays did not result in a detectable transmitted proliferation disadvantage when animals were mated 7 or 12 weeks later. This observation is discussed in light of previous studies on mouse immature oocytes and embryo chimeras

  1. Search for suppression of T cells specific for the second nonhost H-2 haplotype in F1 → P irradiation bone marrow chimeras

    Irradiation bone marrow chimeras were made by lethally irradiating parental (P) mice and reconstituting them with T cell-depleted bone marrow cells from F1 hybrid offsprings. These F1 → P chimeric lymphocytes were then analyzed for suppressor mechanisms that could cause the differentiation of effector T cells whose responsiveness was restricted in specificity to the host parent's H-2 haplotype. No evidence was detected for acute or chronic suppression of the second parent's restriction specificity in tests of cytotoxic T cell activity against virus-infected targets. Therefore, F1 → P irradiation bone marrow chimeras as tested here do not contain mechanisms that suppress the restriction specificity of the second parent, which is not a host to the maturing F1T cells, at least at the effector stage or during differentiation

  2. The Relaxin Receptor (RXFP1) Utilizes Hydrophobic Moieties on a Signaling Surface of Its N-terminal Low Density Lipoprotein Class A Module to Mediate Receptor Activation*

    Kong, Roy C. K.; Petrie, Emma J.; Mohanty, Biswaranjan; Ling, Jason; Lee, Jeremy C. Y.; Gooley, Paul R.; Bathgate, Ross A. D.

    2013-01-01

    The peptide hormone relaxin is showing potential as a treatment for acute heart failure. Although it is known that relaxin mediates its actions through the G protein-coupled receptor relaxin family peptide receptor 1 (RXFP1), little is known about the molecular mechanisms by which relaxin binding results in receptor activation. Previous studies have highlighted that the unique N-terminal low density lipoprotein class A (LDLa) module of RXFP1 is essential for receptor activation, and it has been hypothesized that this module is the true “ligand” of the receptor that directs the conformational changes necessary for G protein coupling. In this study, we confirmed that an RXFP1 receptor lacking the LDLa module binds ligand normally but cannot signal through any characterized G protein-coupled receptor signaling pathway. Furthermore, we comprehensively examined the contributions of amino acids in the LDLa module to RXFP1 activity using both gain-of-function and loss-of-function mutational analysis together with NMR structural analysis of recombinant LDLa modules. Gain-of-function studies with an inactive RXFP1 chimera containing the LDLa module of the human LDL receptor (LB2) demonstrated two key N-terminal regions of the module that were able to rescue receptor signaling. Loss-of-function mutations of residues in these regions demonstrated that Leu-7, Tyr-9, and Lys-17 all contributed to the ability of the LDLa module to drive receptor activation, and judicious amino acid substitutions suggested this involves hydrophobic interactions. Our results demonstrate that these key residues contribute to interactions driving the active receptor conformation, providing further evidence of a unique mode of G protein-coupled receptor activation. PMID:23926099

  3. The relaxin receptor (RXFP1) utilizes hydrophobic moieties on a signaling surface of its N-terminal low density lipoprotein class A module to mediate receptor activation.

    Kong, Roy C K; Petrie, Emma J; Mohanty, Biswaranjan; Ling, Jason; Lee, Jeremy C Y; Gooley, Paul R; Bathgate, Ross A D

    2013-09-27

    The peptide hormone relaxin is showing potential as a treatment for acute heart failure. Although it is known that relaxin mediates its actions through the G protein-coupled receptor relaxin family peptide receptor 1 (RXFP1), little is known about the molecular mechanisms by which relaxin binding results in receptor activation. Previous studies have highlighted that the unique N-terminal low density lipoprotein class A (LDLa) module of RXFP1 is essential for receptor activation, and it has been hypothesized that this module is the true "ligand" of the receptor that directs the conformational changes necessary for G protein coupling. In this study, we confirmed that an RXFP1 receptor lacking the LDLa module binds ligand normally but cannot signal through any characterized G protein-coupled receptor signaling pathway. Furthermore, we comprehensively examined the contributions of amino acids in the LDLa module to RXFP1 activity using both gain-of-function and loss-of-function mutational analysis together with NMR structural analysis of recombinant LDLa modules. Gain-of-function studies with an inactive RXFP1 chimera containing the LDLa module of the human LDL receptor (LB2) demonstrated two key N-terminal regions of the module that were able to rescue receptor signaling. Loss-of-function mutations of residues in these regions demonstrated that Leu-7, Tyr-9, and Lys-17 all contributed to the ability of the LDLa module to drive receptor activation, and judicious amino acid substitutions suggested this involves hydrophobic interactions. Our results demonstrate that these key residues contribute to interactions driving the active receptor conformation, providing further evidence of a unique mode of G protein-coupled receptor activation. PMID:23926099

  4. NHE1 inhibition by amiloride- and benzoylguanidine-type compounds. Inhibitor binding loci deduced from chimeras of NHE1 homologues with endogenous differences in inhibitor sensitivity

    Pedersen, Stine F; King, Scott A; Nygaard, Eva B;

    2007-01-01

    NHE1). Although highly homologous to the amiloride- and HOE-sensitive human NHE1 (hNHE1), AtNHE1 is insensitive to HOE-type and PaNHE1 to both amiloride- and HOE-type compounds. Here we generated chimeras to "knock in" amiloride and HOE sensitivity to PaNHE1, and we thereby identified several NHE1...

  5. Radiation-induced mouse chimeras: a cellular analysis of the major lymphoid compartments, factors affecting lethal graft versus host disease and host-tumor interactions

    The major lymphoid compartments of allogeneic bone marrow chimeras were evaluated for the extent of cell chimerism and distribution of Thy 1 and la bearing cells. These chimeras contained lymphoid cell primarily of donor origin. The bone marrow compartment was a mixture of host and donor origin cells. The distribution of Thy 1 and la bearing cells was similar as in normal mice. The effect of adult thymectomy alone or followed by whole-body irradiation and bone marrow reconstitution on the distribution of the Thy 1 positive cells was also investigated. Thymectomy with or without WBI and bone marrow reconstitution significantly lowered the number of Thy 1 bearing cells in the blood and spleen. The number of la bearing cells did not appear to be affected by thymectomy. The role of circulating lymphoid cells in the incidence of lethal graft versus host disease (GVHD) in radiation induced fully allogeneic mouse chimeras was studied. Mice reconstituted with allogeneic bone marrow from bled donors had a statistically lower incidence of GVHD than those reconstituted with bone marrow from unbled donors. Addition of mature peripheral lymphocytes from blood to the reconstituting bone marrow cells from bled donors reduplicated the high incidence of lethal GVHD. It was demonstrated that the bone marrow of mice not exsanguinated prior to harvesting of bone marrow contained significant numbers of peripheral contaminating cells in the harvested bone marrow. The role of suppressor cell elimination in resisting tumor growth was investigated using radiation induced mouse chimeras. Local effects of irradiation alone at the site of tumor inoculation could account for this lack of growth

  6. H-2-incompatible bone marrow chimeras produce donor-H-2-restricted Ly-2 suppressor T-cell factor(s)

    To study adaptive-differentiation phenomena of T lymphocytes, suppressor T-cell factors (TsF) produced by Ly-2+ splenic T cells from fully allogeneic mouse bone marrow chimeras were analyzed. AKR mice irradiated and reconstituted with B10 marrow cells (B10----AKR chimeras) produced an Ly-2+ TsF after hyperimmunization with sheep erythrocytes. The TsF suppressed primary antibody responses (to sheep erythrocytes) generated with spleen cells of mice of H-2b haplotype but not those of H-2k haplotype. Thus, this suppressor factor was donor-H-2-restricted. The immunoglobulin heavy chain variable region gene (Igh-V)-restricting element was not involved in this form of suppression. Similar results were obtained when TsF from B6----BALB/c and BALB/c----B6 chimeras were analyzed. The TsF from B10----AKR chimeras suppressed responses of B10.A(3R) and B10.A(5R) mice but not those of B10.A(4R). This finding showed that identity between the factor-producing cells and target spleen cells is required on the left-hand side of the E beta locus of the H-2 region and that the putative I-Jb locus is not involved in this form of suppression. The present results support the postulate that post-thymic differentiation in the presence of continued or repeated stimulation with antigen and donor-derived antigen-presenting cells generates donor-H-2-restricted T-cell clones that may predominate within the repertoire of the specific antigen being presented

  7. Increasing the biological activity of IL-2 and IL-15 through complexing with anti-IL-2 mAbs and Il-15Ralfa-Fc chimera

    Votavová, Petra; Tomala, Jakub; Kovář, Marek

    2014-01-01

    Roč. 195, č. 1 (2014), s. 1-10. ISSN 0165-2478 R&D Projects: GA ČR GAP301/11/0325; GA MŠk(CZ) ED1.1.00/02.0109; GA ČR GA13-12885S Institutional support: RVO:61388971 Keywords : IL-2 * IL-15 * chimera Subject RIV: EC - Immunology Impact factor: 2.512, year: 2014

  8. DNA/RNA chimera templates improve the emission intensity and target the accessibility of silver nanocluster-based sensors for human microRNA detection.

    Shah, Pratik; Choi, Suk Won; Kim, Ho-jin; Cho, Seok Keun; Thulstrup, Peter Waaben; Bjerrum, Morten Jannik; Bhang, Yong-Joo; Ahn, Jong Cheol; Yang, Seong Wook

    2015-05-21

    In recent years microRNAs (miRNAs) have been established as important biomarkers in a variety of diseases including cancer, diabetes, cardiovascular disease, aging, Alzheimer's disease, asthma, autoimmune disease and liver diseases. As a consequence, a variety of monitoring methods for miRNAs have been developed, including a fast and simple method for miRNA detection by exploitation of the unique photoluminescence of DNA-templated silver nanoclusters (DNA/AgNCs). To increase the versatility of the AgNC-based method, we have adopted DNA/RNA chimera templates for AgNC-based probes, allowing response from several human miRNAs which are hardly detectable with DNA-based probes. Here, we demonstrate in detail the power of DNA/RNA chimera/AgNC probes in detecting two human miRNAs, let-7a and miR-200c. The DNA/RNA chimera-based probes are highly efficient to determine the level of miRNAs in several human cell lines. PMID:25759134

  9. Management of Chimera and In Vitro Mutagenesis for Development of New Flower Color/Shape and Chlorophyll Variegated Mutants in Chrysanthemum

    Mutation breeding is an established method for crop improvement and has played a major role in the development of many new flower color/shape mutant varieties in ornamentals. The main bottleneck with vegetatively propagated plants is that the mutation appears as a chimera after treatment with physical and/or chemical mutagens. A small sector of a mutated branch or flower cannot be isolated using the available conventional propagation techniques. A novel technique has been standardized for the management of such chimeric tissues through direct shoot regeneration from chrysanthemum florets. This direct novel regeneration protocol has been successfully used not only for the isolation of chimeric mutant tissues developed through sports, but also to develop a series of new flower color/shape mutants through induced mutagenesis. Gamma radiation and tissue culture techniques have been optimized to regenerate plants from stem internodes, stem nodes, shoot tips and ray florets for in vitro management of chimera and for in vitro mutagenesis. Chimera isolation has practical importance not only for chrysanthemum but for breeding of other ornamentals also. The present technique will open up a new way for isolating new flower color/shape ornamental cultivars through retrieval of mutated cells. (author)

  10. The use of the mouse chimera assay to detect early embryonic damage from male mice exposed to low-dose radiation

    Mouse chimeras are in vitro aggregations of two 4-cell embryos and are used to detect subtle, nonlethal changes, which are expressed as a proliferative disadvantage in exposed embryos. One of the embryos is labeled with a viable dye (FITC) in order to determine the relative cellular contribution of each embryo when the chimera is dissociated 40 hours later. This proliferative disadvantage has been seen at doses which do not produce an effect on cell number when the embryos are cultured singly. Previously, the assay has detected a decrease in cellular proliferation in embryos from male mice exposed to a single dose of x-radiation as low as 0.05 Gy. In the current study, male mice were irradiated with a single dose of 0, 0.001, 0.01, or 0.05 Gy, and then serially mated for the next 8 weeks to unexposed females. Chimeras were constructed from control and treated embryos. Embryos from males treated with 0.05 Gy exhibited a significant decrease in cellular proliferation during weeks 6 and 7 post-irradiation. A similar decrease was seen in the males treated with 0.01 Gy. No reductions were observed from embryos cultured singly in any of the treatment groups

  11. Clonal deletion of self-reactive T cells in irradiation bone marrow chimeras and neonatally tolerant mice. Evidence for intercellular transfer of Mlsa

    Tolerance to Mlsa has been shown to be associated with clonal deletion of cells carrying TCR beta chain variable regions V beta 6 or V beta 8.1 in mice possessing I-E antigens. To evaluate the rules of tolerance induction to Mlsa we prepared irradiation bone marrow chimeras expressing Mlsa or Mlsb and I-E by different cell types. Deletion of V beta 6+, Mlsa-reactive T cells required the presence of Mlsa and I-E products either on bone marrow-derived cells or on irradiated recipient cells. Tolerance was induced when Mlsa and I-E were expressed by distinct cells of the chimera. Also neonatally tolerized mice exhibited depletion of V beta 6+ cells after injection of I-E- Mlsa spleen cells (DBA/1) into newborn I-E+ Mlsb mice (BALB/c x B10.G)F1. These results suggest that the product of the Mlsa locus is soluble and/or may be transferred from cell to cell and bound to I-E antigens. The chimera experiments also showed that tolerance to Mlsa is H-2 allele independent, i.e., is apparently unrestricted. Differentiation of chimeric (H-2d/Mlsa x H-2q/Mlsb)F1 stem cells in either an H-2d or an H-2q thymus revealed that tolerance assessed by absence of V beta 6+ T cells is not dependent on the thymically determined restriction specificity of T cells

  12. Calcium and cargoes as regulators of myosin 5a activity

    Myosin 5a is a two-headed actin-dependent motor that transports various cargoes in cells. Its enzymology and mechanochemistry have been extensively studied in vitro. It is a processive motor that takes multiple 36 nm steps on actin. The enzymatic activity of myosin 5 is regulated by an intramolecular folding mechanism whereby its lever arms fold back against the coiled-coil tail such that the motor domains directly bind the globular tail domains. We show that the structure seen in individual folded molecules is consistent with electron density map of two-dimensional crystals of the molecule. In this compact state, the actin-activated MgATPase activity of the molecule is markedly inhibited and the molecule cannot move processively on surface bound actin filaments. The actin-activated MgATPase activity of myosin 5a is activated by increasing the calcium concentration or by binding of a cargo-receptor molecule, melanophilin, in vitro. However, calcium binding to the calmodulin light chains results in dissociation of some of the calmodulin which disrupts the ability of myosin 5a to move on actin filaments in vitro. Thus we propose that the physiologically relevant activation pathway in vivo involves binding of cargo-receptor proteins

  13. Absolute quantification of dengue virus serotype 4 chimera vaccine candidate in Vero cell culture by targeted mass spectrometry.

    Rougemont, Blandine; Simon, Romain; Carrière, Romain; Biarc, Jordane; Fonbonne, Catherine; Salvador, Arnaud; Huillet, Céline; Berard, Yves; Adam, Olivier; Manin, Catherine; Lemoine, Jérôme

    2015-10-01

    Infection by dengue flavivirus is transmitted by mosquitoes and affects tens to hundreds of millions people around the world each year. Four serotypes have been described, all of which cause similar disease. Currently, there no approved vaccines or specific therapeutics for dengue, although several vaccine prototypes are in different stages of clinical development. Among them, a chimeric vaccine, built from the replication machinery of the yellow fever 17D virus, has shown promising results in phase III trials. Accurate quantitation of expressed viral particles in alive attenuated viral antigen vaccine is essential and determination of infectious titer is usually the method of choice. The current paper describes an alternative or orthogonal strategy, namely, a multiplexed and absolute assay of four proteins of the chimera yellow fever/dengue serotype 4 virus using targeted MS in SRM mode. Over 1 month, variability of the assay using a partially purified Vero cell extract was between 8 and 17%, and accuracy was between 80 and 120%. In addition, the assay was linear between 6.25 and 200 nmol/L and could therefore be used in the near future to quantify dengue virus type 4 during production and purification from Vero cells. PMID:26205729

  14. Particle gamma correlations in {sup 12}C measured with the CsI(Tl) based detector array CHIMERA

    Cardella, G., E-mail: cardella@ct.infn.it [INFN - Sezione di Catania, Via S. Sofia, 95123 Catania (Italy); Acosta, L. [INFN - Sezione di Catania, Via S. Sofia, 95123 Catania (Italy); Amorini, F. [INFN - Laboratori Nazionali del Sud, Via S. Sofia, Catania (Italy); Auditore, L. [INFN Gruppo collegato di Messina and Dip. di Fisica e Scienze della Terra, Università di Messina (Italy); Berceanu, I. [Institute for Physics and Nuclear Engineering, Bucharest (Romania); Castoldi, A. [INFN Sezione di Milano e Politecnico Milano (Italy); De Filippo, E. [INFN - Sezione di Catania, Via S. Sofia, 95123 Catania (Italy); Dell' Aquila, D. [Dipartimento di scienze Fisiche, Università Federico II and INFN Sezione di Napoli (Italy); Francalanza, L. [INFN - Laboratori Nazionali del Sud, Via S. Sofia, Catania (Italy); Dip. di Fisica e Astronomia, Università di Catania, Via S. Sofia, Catania (Italy); Gnoffo, B. [INFN - Sezione di Catania, Via S. Sofia, 95123 Catania (Italy); Guazzoni, C. [INFN Sezione di Milano e Politecnico Milano (Italy); Lanzalone, G. [INFN - Laboratori Nazionali del Sud, Via S. Sofia, Catania (Italy); Facoltà di Ingegneria e Architettura, Università Kore, Enna (Italy); Lombardo, I. [Dipartimento di scienze Fisiche, Università Federico II and INFN Sezione di Napoli (Italy); Minniti, T.; Morgana, E.; Norella, S. [INFN Gruppo collegato di Messina and Dip. di Fisica e Scienze della Terra, Università di Messina (Italy); Pagano, A. [INFN - Sezione di Catania, Via S. Sofia, 95123 Catania (Italy); Pagano, E.V. [INFN - Laboratori Nazionali del Sud, Via S. Sofia, Catania (Italy); Dip. di Fisica e Astronomia, Università di Catania, Via S. Sofia, Catania (Italy); Papa, M.; Pirrone, S. [INFN - Sezione di Catania, Via S. Sofia, 95123 Catania (Italy); and others

    2015-11-01

    The gamma decay of the first excited 4.44 MeV 2+level of {sup 12}C, populated by inelastic scattering of proton and {sup 16}O beams at various energies was studied in order to test γ-ray detection efficiency and the quality of angular distribution information given by the CsI(Tl) detectors of the 4π CHIMERA array. The γ-decay was measured in coincidence with ejectile scattered particles in an approximately 4π geometry allowing to extract the angular distribution in the reference frame of recoiling {sup 12}C target. The typical sin{sup 2} (2θ) behavior of angular distribution was observed in the case of {sup 16}O beam. Besides that, for the proton beam, in order to explain the observed distribution, the addition of an incoherent flat contribution was required. This latter is the effect of proton spin flip events allowing the population of M=±1 magnetic substates, that is not possible in reactions induced by {sup 16}O beam. A comparison with previously collected data, obtained measuring only in and out of plane proton-γ-ray coincidences, confirms the good quality of the angular distribution information given by the apparatus. Possible applications with radioactive beams are outlined.

  15. Influence of Linker Length Variations on the Biomass-Degrading Performance of Heat-Active Enzyme Chimeras.

    Rizk, Mazen; Antranikian, Garabed; Elleuche, Skander

    2016-04-01

    Plant cell walls are composed of complex polysaccharides such as cellulose and hemicellulose. In order to efficiently hydrolyze cellulose, the synergistic action of several cellulases is required. Some anaerobic cellulolytic bacteria form multienzyme complexes, namely cellulosomes, while other microorganisms produce a portfolio of diverse enzymes that work in synergistic fashion. Molecular biological methods can mimic such effects through the generation of artificial bi- or multifunctional fusion enzymes. Endoglucanase and β-glucosidase from extremely thermophilic anaerobic bacteria Fervidobacterium gondwanense and Fervidobacterium islandicum, respectively, were fused end-to-end in an approach to optimize polysaccharide degradation. Both enzymes are optimally active at 90 °C and pH 6.0-7.0 representing excellent candidates for fusion experiments. The direct linkage of both enzymes led to an increased activity toward the substrate specific for β-glucosidase, but to a decreased activity of endoglucanase. However, these enzyme chimeras were superior over 1:1 mixtures of individual enzymes, because combined activities resulted in a higher final product yield. Therefore, such fusion enzymes exhibit promising features for application in industrial bioethanol production processes. PMID:26921187

  16. Chimeras Reveal a Single Lipid-Interface Residue that Controls MscL Channel Kinetics as well as Mechanosensitivity

    Li-Min Yang

    2013-02-01

    Full Text Available MscL, the highly conserved bacterial mechanosensitive channel of large conductance, serves as an osmotic “emergency release valve,” is among the best-studied mechanosensors, and is a paradigm of how a channel senses and responds to membrane tension. Although all homologs tested thus far encode channel activity, many show functional differences. We tested Escherichia coli and Staphylococcus aureus chimeras and found that the periplasmic region of the protein, particularly E. coli I49 and the equivalent S. aureus F47 at the periplasmic lipid-aqueous interface of the first transmembrane domain, drastically influences both the open dwell time and the threshold of channel opening. One mutant shows a severe hysteresis, confirming the importance of this residue in determining the energy barriers for channel gating. We propose that this site acts similarly to a spring for a clasp knife, adjusting the resistance for obtaining and stabilizing an open or closed channel structure.

  17. Restriction of germline proliferation by soft x-ray irradiation of chicken embryos and its application to chimera production

    Primordial germ cells (PGCs) are the progenitor cells of gametes. Avian PGCs are located in the central region of the area pellucida at the blastoderm stage. PGCs enter the circulation soon after the formation of blood vessels in incubating eggs and eventually settle in the gonadal primordium. We have now examined exposure of chicken embryos to soft (low-energy) x-rays as a means of depleting endogenous PGCs and thereby improving the efficiency of chimera production. The blastoderm of White Leghorn eggs was exposed to soft x-rays for 0, 20, 40 or 60 s before incubation. The irradiated embryos manifested delayed development at 60 h of incubation. They also showed reduced numbers of circulating PGCs at stages 14 and 15 and of gonadal PGCs at stage 30. The hatchability of irradiated embryos was lower than that of nonirradiated controls. Irradiation for 20 s was found to provide the best outcome taking into consideration both the restriction of PGC proliferation and hatchability. Dispersed blastoderm cells of quail (black plumage) embryos were introduced into the blastoderm of chicken embryos irradiated for 20 s or of nonirradiated embryos. The number of donor-derived PGCs was higher in the irradiated embryos than in the nonirradiated controls at stage 30. These results suggest that soft x-irradiation of chicken embryos is a feasible approach to depletion of endogenous germ cells and consequent improvement in the efficiency of incorporation of donor PGCs

  18. Design, synthesis and DNA interactions of a chimera between a platinum complex and an IHF mimicking peptide.

    Rao, Harita; Damian, Mariana S; Alshiekh, Alak; Elmroth, Sofi K C; Diederichsen, Ulf

    2015-12-28

    Conjugation of metal complexes with peptide scaffolds possessing high DNA binding affinity has shown to modulate their biological activities and to enhance their interaction with DNA. In this work, a platinum complex/peptide chimera was synthesized based on a model of the Integration Host Factor (IHF), an architectural protein possessing sequence specific DNA binding and bending abilities through its interaction with a minor groove. The model peptide consists of a cyclic unit resembling the minor grove binding subdomain of IHF, a positively charged lysine dendrimer for electrostatic interactions with the DNA phosphate backbone and a flexible glycine linker tethering the two units. A norvaline derived artificial amino acid was designed to contain a dimethylethylenediamine as a bidentate platinum chelating unit, and introduced into the IHF mimicking peptides. The interaction of the chimeric peptides with various DNA sequences was studied by utilizing the following experiments: thermal melting studies, agarose gel electrophoresis for plasmid DNA unwinding experiments, and native and denaturing gel electrophoresis to visualize non-covalent and covalent peptide-DNA adducts, respectively. By incorporation of the platinum metal center within the model peptide mimicking IHF we have attempted to improve its specificity and DNA targeting ability, particularly towards those sequences containing adjacent guanine residues. PMID:26477860

  19. Interspecies avian brain chimeras reveal that large brain size differences are influenced by cell-interdependent processes.

    Chen, Chun-Chun; Balaban, Evan; Jarvis, Erich D

    2012-01-01

    Like humans, birds that exhibit vocal learning have relatively delayed telencephalon maturation, resulting in a disproportionately smaller brain prenatally but enlarged telencephalon in adulthood relative to vocal non-learning birds. To determine if this size difference results from evolutionary changes in cell-autonomous or cell-interdependent developmental processes, we transplanted telencephala from zebra finch donors (a vocal-learning species) into Japanese quail hosts (a vocal non-learning species) during the early neural tube stage (day 2 of incubation), and harvested the chimeras at later embryonic stages (between 9-12 days of incubation). The donor and host tissues fused well with each other, with known major fiber pathways connecting the zebra finch and quail parts of the brain. However, the overall sizes of chimeric finch telencephala were larger than non-transplanted finch telencephala at the same developmental stages, even though the proportional sizes of telencephalic subregions and fiber tracts were similar to normal finches. There were no significant changes in the size of chimeric quail host midbrains, even though they were innervated by the physically smaller zebra finch brain, including the smaller retinae of the finch eyes. Chimeric zebra finch telencephala had a decreased cell density relative to normal finches. However, cell nucleus size differences between each species were maintained as in normal birds. These results suggest that telencephalic size development is partially cell-interdependent, and that the mechanisms controlling the size of different brain regions may be functionally independent. PMID:22860132

  20. Interspecies avian brain chimeras reveal that large brain size differences are influenced by cell-interdependent processes.

    Chun-Chun Chen

    Full Text Available Like humans, birds that exhibit vocal learning have relatively delayed telencephalon maturation, resulting in a disproportionately smaller brain prenatally but enlarged telencephalon in adulthood relative to vocal non-learning birds. To determine if this size difference results from evolutionary changes in cell-autonomous or cell-interdependent developmental processes, we transplanted telencephala from zebra finch donors (a vocal-learning species into Japanese quail hosts (a vocal non-learning species during the early neural tube stage (day 2 of incubation, and harvested the chimeras at later embryonic stages (between 9-12 days of incubation. The donor and host tissues fused well with each other, with known major fiber pathways connecting the zebra finch and quail parts of the brain. However, the overall sizes of chimeric finch telencephala were larger than non-transplanted finch telencephala at the same developmental stages, even though the proportional sizes of telencephalic subregions and fiber tracts were similar to normal finches. There were no significant changes in the size of chimeric quail host midbrains, even though they were innervated by the physically smaller zebra finch brain, including the smaller retinae of the finch eyes. Chimeric zebra finch telencephala had a decreased cell density relative to normal finches. However, cell nucleus size differences between each species were maintained as in normal birds. These results suggest that telencephalic size development is partially cell-interdependent, and that the mechanisms controlling the size of different brain regions may be functionally independent.

  1. Control of Ixodes ricinus and Dermacentor reticulatus tick infestations in rabbits vaccinated with the Q38 Subolesin/Akirin chimera.

    Contreras, Marinela; de la Fuente, José

    2016-06-01

    Diseases transmitted by ticks greatly impact human and animal health and their control is important for the eradication of tick-borne diseases. Vaccination is an environmentally friendly alternative for tick control. Recent results have suggested that Subolesin/Akirin (SUB/AKR) are good candidate antigens for the control of arthropod vector infestations. Here, we describe the effect of vaccination with the Q38 chimera containing SUB/AKR conserved protective epitopes on Ixodes ricinus and Dermacentor reticulatus tick larval mortality, feeding and molting. We demonstrated that Q38 vaccination had an efficacy of 99.9% and 46.4% on the control of I. ricinus and D. reticulatus larvae by considering the cumulative effect on reducing tick survival and molting. The effect of the Q38 vaccine on larval feeding and molting is essential to reduce tick infestations and supports that Q38 might be a candidate universal antigen for the control of multiple tick species that can infest the same host. PMID:27154388

  2. Factors affecting immune responsiveness in vitro of germfree allogeneic radiation chimeras. I. Differences between donor and host strains

    An important aspect of bone marrow transplantation has been focused upon. It has been demonstrated that significant differences between in vitro responses of germfree DBA/2 mice (donor strain) and of C3H/He (recipient strain) exist. The PHA response of spleen cells from germfree C3H/He mice is greater than that of DBA/2 mice. However, the reverse is true in regard to Con A responsiveness. In fact, calculation of a Con A/PHA ratio reveals a striking difference between strains. B cell reactivity as assessed by LPS mitogenic responsiveness is similar in both strains. The cell mediated responsiveness of DBA/2 mice is also diminished as measured by mixed lymphocyte reaction and cell mediated cytotoxicity. An inverse correlation between plaque forming cell (PFC) responses in vitro and the Con A/PHA ratio in DBA/2 mice is suggestive of a predominance of inherent suppressor cell activity in this strain. These characteristics of the DBA/2 immune responsiveness may be a factor in the apparent T cell unresponsiveness seen in DBA/2 leads to C3H/He mouse allogeneic bone marrow chimeras

  3. Particle gamma correlations in 12C measured with the CsI(Tl) based detector array CHIMERA

    Cardella, G.; Acosta, L.; Amorini, F.; Auditore, L.; Berceanu, I.; Castoldi, A.; De Filippo, E.; Dell`Aquila, D.; Francalanza, L.; Gnoffo, B.; Guazzoni, C.; Lanzalone, G.; Lombardo, I.; Minniti, T.; Morgana, E.; Norella, S.; Pagano, A.; Pagano, E. V.; Papa, M.; Pirrone, S.; Politi, G.; Pop, A.; Quattrocchi, L.; Rizzo, F.; Rosato, E.; Russotto, P.; Trifirò, A.; Trimarchi, M.; Verde, G.; Vigilante, M.

    2015-11-01

    The gamma decay of the first excited 4.44 MeV 2+level of 12C, populated by inelastic scattering of proton and 16O beams at various energies was studied in order to test γ-ray detection efficiency and the quality of angular distribution information given by the CsI(Tl) detectors of the 4π CHIMERA array. The γ-decay was measured in coincidence with ejectile scattered particles in an approximately 4π geometry allowing to extract the angular distribution in the reference frame of recoiling 12C target. The typical sin2 (2θ) behavior of angular distribution was observed in the case of 16O beam. Besides that, for the proton beam, in order to explain the observed distribution, the addition of an incoherent flat contribution was required. This latter is the effect of proton spin flip events allowing the population of M=±1 magnetic substates, that is not possible in reactions induced by 16O beam. A comparison with previously collected data, obtained measuring only in and out of plane proton-γ-ray coincidences, confirms the good quality of the angular distribution information given by the apparatus. Possible applications with radioactive beams are outlined.

  4. 花烛突变体叶色嵌合性状的分化特征与保持方法%Differentiation characteristics and retention method of leaf color chimera feature of mutated plantlet of Anthurium andraeanum

    陈星旭; 邵会会; 王广东

    2011-01-01

    Using asepsis seedlings of leaf color chimera type of Anthurium andraeanum ' Sonate' as the experimental materials, single-bud cultures of sixteen individuals without top bud chimera feature were carried out, and differentiation characteristics of leaf color chimera feature during regeneration process of axillary bud and stem basal part were observed. And based on observation results, the retention method of leaf color chimera feature of mutated plantlet of A. Andraeanum was summed up. The results show that chimera percentage of regenerated plantlets from axillary buds of mutated plantlets in proliferation and rooting phases is 25.0%-75.0% and 25.0%-66.7% and total chimera percentage is 48.4% and 47. 8% , respectively. The regenerated plantlets from axillary buds with chimera feature are all burgeoned from axils of chimera leaves. And chimera plantlet can also be regenerated from the stem basal part of mutated plantlets in rooting phase with a chimera percentage of 33. 3% -80. 0% and total chimera percentage of 64. 7%. It is concluded that the problem of losing leaf color chimera feature of top bud of mutated plantlet of A. Andraeanum could be resolved by single-bud in vitro culture. And chimera feature of mutated plantlet can be retained with axillary bud (in proliferation and rooting phases) and basal part (in rooting phase) regeneration cultures.%以花烛品种‘Sonate’(Anthurium andraeanum‘Sonate’)的叶色嵌合型无菌苗为材料,对顶芽失去嵌合性状的16个单株分别进行单芽培养,观察侧芽及茎基部再生过程中叶色嵌合性状的分化特征;并据此归纳花烛突变体叶色嵌合性状的保持方法.结果表明:处于增殖和生根阶段的花烛突变单株侧芽再生植株的嵌合率分别为25.0%~75.0%和25.0% ~ 66.7%,总的嵌合率分别为48.4%和47.8%,具有嵌合性状的侧芽再生植株均萌发于嵌合叶片的叶腋处;处于生根阶段的突变单株的茎基部也能再生出

  5. Functional Identification of the Stable Transfection C5aR Cell Line Molt-4

    Chunmei Zhang; Yan Li; Ruonan Xu; Jianan Wang; Gencheng Han; Guojiang Chen; Renxi Wang; Huawei Wei; Beifen Shen; Yuanfang Ma

    2007-01-01

    The complement C5 anaphylatoxin receptor is a member of the seven transmembrane-spanning G protein-coupled receptor superfamily that signals through Gαi and Gα16. C5aR is mostly expressed on neutrophils, macrophages and endothelial cells. C5a and C5aR interaction plays an important role in numerous biological effects such as in vivo cytokine storm which results in inflammatory damage. Considering the limitation of collection of human peripheral blood neutrophils and their short half life, the stably transfected cell line for studying the biological effects of C5aR is needed. In this study, we transfected C5aR gene into Molt-4 cell line and examined the function of ectopic C5aR. Our results showed stable expression of the C5aR in Molt-4 cell line and their interaction with human C5a induced ERK1/2 phosphorylation, Ca++ influx. This stable transfected cell line may provide a useful tool for studying signal pathways related to C5a and C5aR interplay and antibody development specific for C5aR.

  6. Lipoxin Receptors

    Mario Romano

    2007-01-01

    Full Text Available Lipoxins (LXs represent a class of arachidonic acid (AA metabolites that carry potent immunoregulatory and anti-inflammatory properties, LXA4 and LXB4 being the main components of this series. LXs are generated by cooperation between 5-lipoxygenase (LO and 12- or 15-LO during cell-cell interactions or by single cell types. LX epimers at carbon 15, the 15-epi-LXs, are formed by aspirin-acetylated cyclooxygenase-2 (COX-2 in cooperation with 5-LO. 15-epi-LXA4 is also termed aspirin-triggered LX (ATL. In vivo studies with stable LX and ATL analogs have established that these eicosanoids possess potent anti-inflammatory activities. A LXA4 receptor has been cloned. It belongs to the family of chemotactic receptors and clusters with formyl peptide receptors on chromosome 19. Therefore, it was initially denominated formyl peptide receptor like 1 (FPRL1. This receptor binds with high affinity and stereoselectivity LXA4 and ATL. It also recognizes a variety of peptides, synthetic, endogenously generated, or disease associated, but with lower affinity compared to LXA4. For this reason, this receptor has been renamed ALX. This review summarizes the current knowledge on ALX expression, signaling, and potential pathophysiological role. The involvement of additional recognition sites in LX bioactions is also discussed.

  7. Wnt5a regulates growth, patterning, and odontoblast differentiation of developing mouse tooth

    Lin, Minkui; Li, Lu; Liu, Chao; Hongbing LIU; He, Fenglei; Yan, Fuhua; Zhang, Yanding; Chen, Yiping

    2011-01-01

    Wnt/β-catenin signaling is essential for tooth development beyond the bud stage, but little is known about the role of non-canonical Wnt signaling in odontogenesis. Here we compared the expression of Wnt5a, a representative of noncanonical Wnts, with that of Ror2, the Wnt5a receptor for non-canonical signaling, in the developing tooth, and analyzed tooth phenotype in Wnt5a mutants. Wnt5a deficient mice exhibit retarded tooth development beginning from E16.5, leading to the formation of smalle...

  8. Chimera-free, high copy number YAC libraries and efficient methods of analysis. Final technical progress report

    NONE

    1995-10-01

    The first experiment involved a low chimera YAC library in recombination deficient host strains. To determine if the genetic background of the yeast host strain contributes to the formation of chimeric YACs the same YAC ligation mixture was introduced into three isogenic yeast hosts differing only in their recombination abilities. To prepare YACs, human genomic DNA was partially digested with EcoR1 and then ligated to YAC vector pCGS966 arms. DNA was size fractionated before and after ligation by preparative pulsed field gel electrophoresis (CHEF), selecting for fragments greater than 400 kb, and introduced into competent spheroplasts. CHEF gel Southern blots of resulting colony-purified YACs were probed with human DNA to determine if multiple YACs or YAC fragments were present in the same cell. The frequency of chimeric YACs was measured by fluorescence in situ hybridization (FISH) of YACs to human prometaphase spreads. YACs that hybridized to more than one location were assumed to be chimeric. In the second experiment new YAC vectors featuring tags for capture of YACs and YAC inserts were constructed. Yeast Artificial Chromosomes (YACs) have been of tremendous value in the physical mapping of the human genome. Because they can carry very large inserts, YACs are likely not only to contain entire genes but also their control elements. However, the only mode of purification of YAC DNA from current commonly used YAC libraries such as the CEPH library is by pulsed field gel electrophoresis. This is an inefficient, time consuming process and due to the single copy nature of these YACs, often result in poor yields. The vector pCGS1000 was designed to test new efficient ways of YAC DNA purification.

  9. Construction, Expression, and Characterization of a Recombinant Annexin B1-Low Molecular Weight Urokinase Chimera in Escherichia coli

    Hong-Li YAN; Wei-Ting WANG; Yan HE; Zhuan-You ZHAO; Yuan-Jian GAO; Yi ZHANG; Shu-Han SUN

    2004-01-01

    To produce a thrombi-targeting plasminogen activator,low molecular weight single-chain urokinase gene(scuPA32k)was spliced with the full-length cDNA of annexin B 1 gene(anxB1)by overlap extension method.The fused gene anxBlscuPA was ligated into pET28a vector,transformed into E.coli BL21-RIL,and then induced to express under the control of T7 promoter.The AnxB 1ScuPA protein expressed amounted to 22% of the total bacterial proteins.The product was refolded,and then purified by using DEAE Sepharose fast flow ion-exchange column and Superdex S-200 gel-filtration column.HPLC analysis revealed that the final purity is about 95%.The specific activity ofAnxB 1ScuPA,measured as amidolytic activity,reached 100,000 IU/mg.It had a similar S2444 catalytic efficiency(kcat/Km)to ScuPA32k,and also showed high activated-platelet membrane-binding activity and anticoagulant activity,indicating that the chimera fully retained the components of enzymatic and membrane-binding activities of the parent molecules.In vivo test revealed that,the dogs administered with AnxB 1ScuPA had less reperfusion time,higher reperfusion ratio,and less bleeding effects than those with urokinase.These findings indicated that AnxB 1ScuPAmight have advantages over current available thrombolytic agents.

  10. Soluble Jagged 1/Fc chimera protein induces the differentiation and maturation of bone marrow-derived dendritic cells

    XING FeiYue; LIU Jing; YU Zhe; JI YuHua

    2008-01-01

    A soluble Jagged 1/Fc chimera protein (Jagged 1/Fc) was directly used to induce differentiation and maturation of bone marrow-derived dendritic cells (DCs) in mice in vitro. A model of inducing and am-plifying DCs in vitro was established. The effect of Jagged 1/Fc on morphology of DCs induced by both rmGM-CSF and rmlL-4 was observed under a confocal microscope. A fluorescein-labeled monoclonal antibody staining combined with flow cytometry was applied to detect the effect of Jagged 1/Fc on the expression of CD11c, MHC-Ⅱ, CD86, CD80 and CD40 molecules on the surface of DCs. The results showed that Jagged 1/Fc did not affect the morphological properties of DC differentiation induced by both rmGM-CSF and rmlL-4. But it could promote the differentiation and maturation of DCs induced by both. The effect of it was strikingly different in the expression profile of co-stimulating molecules and the morphologic properties of DCs from lipopolysaccharide (LPS). The levels of MHC-Ⅱ and CD40 molecule expression on the surface of DCs stimulated by Jagged 1/Fc were significantly lower than those stimulated by LPS, and the level of CD80 expression on the surface of DCs induced by Jagged 1/Fc was near to that induced by LPS. Jagged 1/Fc had no influence on the expression of CD86 mole-cule on the surface of DCs. Jagged 1/Fc when used alone could not maintain the growth, differentiation and maturation of DCs. All the findings indicate that Jagged 1/Fc influences the differentiation and maturation of DCs, which is not markedly similar to LPS, providing important evidence for its devel-opment and application as a novel immunosuppressant.

  11. Recipient micro-environment does not dictate the Igh-V restriction specificity of T cell suppressor inducer factor (TsiF) from allogeneic bone marrow chimera in mice

    The authors have ascertained previously from a study of fully allogeneic irradiation chimeras in mice that the H-2 restriction of the suppressor factor (Ly-2 T suppressor factor) is determined by the post-thymic environment protected by the donor cells, rather than by the thymic environment of the recipient. In the present study, the author analyzed differentiation influences that determine the Igh restriction specificities of the suppressor inducer T cell factor(s) (TsiF) that are produced by Ly-1+ splenic T cells in fully allogeneic bone marrow chimeras in mice. AKR mice that had been lethally irradiated and reconstituted with B10 marrow cells, [B10----AKR] chimeras, produced Ly-1 TsiF after hyper-immunization with sheep erythrocytes (SRBC) which suppressed antigen--specifically the primary antibody responses to SRBC that were generated in cells of the same Igh-Vb haplotype of donor strain and not those generated in cells of the recipient Igh-Va type. Similar results were obtained when Ly-1 TsiF from [B6----BALB/c] and [BALB/c----B6] chimeras were analyzed. Furthermore, the Ly-1 TsiF from [BALB/c----B6] chimeras suppressed the primary antibody responses of both BALB/c [H-2d, Igh-Va, Igh-Ca] and BAB-14 (H-2d, Igh-Va, Igh-Cb), but not those of CAL-20 (H-2d, Igh-Vd, Igh-Cd). These results demonstrate clearly that the Ly-1 TsiF from allogeneic bone marrow chimeras are donor Igh-V-restricted and are not influenced by the recipient micro-environment, presumably that were provided by the thymuses of the recipient mice

  12. Leucyl-leucine methyl ester treatment of donor cells permits establishment of immunocompetent parent----F1 chimeras that are selectively tolerant of host alloantigens

    Thiele, D.L.; Calomeni, J.A.; Lipsky, P.E.

    1987-10-01

    Treatment of murine lymphocytes with L-leucyl-L-leucine methyl ester (Leu-Leu-OMe) selectively removes natural killer cells, cytotoxic T lymphocyte precursors, and the capacity to cause lethal graft-vs-host disease, whereas bone marrow stem cell function and alloantigen-induced L3T4+ T helper function remains intact. The present studies assess the immunocompetence of allogeneic bone marrow chimeras established by reconstituting irradiated (C57BL/6 X DBA/2)F1 (B6D2F1) mice with Leu-Leu-OMe-treated C57BL/6 (B6) bone marrow and spleen cells. Spleen cells from such chimeras were found to have normal B and T cell mitogenic responses. Furthermore, levels of natural-killer cell function were comparable to those observed in B6----B6 syngeneic radiation chimeras established without Leu-Leu-OMe treatment of donor cells. Spleen cells from B6----B6D2F1 mice were identical with B6----B6 or B6 mice in allostimulatory capacity and thus contained no discernible cells of non-H-2b phenotype. Whereas B6----B6D2F1 spleen cells demonstrated alloproliferative and allocytotoxic responses toward H-2k bearing spleen cells, no H-2d specific proliferative or cytotoxic responses could be elicited. B6----B6D2F1 spleen cells did not suppress the generation of anti-H-2d or anti-H-2k proliferative or cytotoxic responses from control B6 spleen cells. Furthermore, addition of rat concanavalin A supernatants did not reconstitute anti-H-2d responses of B6----B6D2F1 chimeric spleen cells. Thus, Leu-Leu-OMe treatment of B6 donor cells not only prevents lethal graft-vs-host disease, but also permits establishment of long-lived parent----F1 chimeras that are selectively tolerant of host H-2 disparate alloantigens, but fully immunocompetent with respect to natural killer cell function, B and T cell mitogenesis, and anti-third party alloresponsiveness.

  13. Prevention of graft-versus-host disease by treatment of bone marrow with gliotoxin in fully allogeneic chimeras and their cytotoxic T cell repertoire

    Gliotoxin, a secondary fungal metabolite, at nanomolar concentrations, irreversibly inhibits murine T cell proliferation to mitogen. Treatment of allogeneic spleen cells with gliotoxin allows their transfer into sublethally irradiated recipients without inducing a GVH reaction. Gliotoxin treatment of bone marrow allows the establishment of fully allogenic bone marrow chimeras free of GVH disease. The cytotoxic T cell repertoire against influenza virus in these animals is restricted to both host- and donor-type MHC. However, their immune competence is severely compromised by their lack of host MHC-type stimulator cells

  14. Clonal deletion of self-reactive T cells at the early stage of T cell development in thymus of radiation bone marrow chimeras

    Sequential appearance of T cell subpopulations occurs in the thymocytes of irradiated C3H/He mice (H-2k, Mls-1b2a, Thy-1.2) after transplantation with bone marrow cells of AKR/J mice (H-2k, Mls-1a2b, Thy-1.1) (AKR----C3H chimeras). The donor-derived thymocytes of AKR----C3H chimeras on day 14 after bone marrow transplantation (BMT) contained a large number of blastlike CD4+CD8+ cells which represent relatively immature thymocytes, whereas those on day 21 after BMT consisted of small sized CD4+,CD8+ cells which represent a great part in normal thymocytes. To define the developmental stage at which clonal deletion of self-reactive T cells occurs in adult thymus, we followed the fate of V beta 6- or V beta 11-bearing T cells in the donor-derived thymocytes at the early stage of AKR----C3H chimeras. Mature thymocytes expressing high intensity of V beta 6 or V beta 11, which are involved in recognition of Mls-1a or MHC I-E gene products, respectively, were deleted from the donor-derived thymocytes on day 21. Immature thymocytes expressing low intensity of V beta 6 in CD3low thymocyte fraction decreased in proportion, whereas those expressing low intensity of V beta 11 rather increased in proportion in the donor-derived thymocytes of AKR----C3H chimeras from day 14 to day 21 after BMT. These results suggest that the clonal deletion of V beta 6-positive cells occurs just at the stage of immature CD3lowCD4+CD8+ cells, whereas the clonal deletion of V beta 11-positive cells may begin at the transitional stage from CD3lowCD4+CD8+ cells to CD3high single positive cells. Timing of negative selection of thymocytes may vary in distinct T cells capable of recognizing different self-Ag

  15. Leucyl-leucine methyl ester treatment of donor cells permits establishment of immunocompetent parent----F1 chimeras that are selectively tolerant of host alloantigens

    Treatment of murine lymphocytes with L-leucyl-L-leucine methyl ester (Leu-Leu-OMe) selectively removes natural killer cells, cytotoxic T lymphocyte precursors, and the capacity to cause lethal graft-vs-host disease, whereas bone marrow stem cell function and alloantigen-induced L3T4+ T helper function remains intact. The present studies assess the immunocompetence of allogeneic bone marrow chimeras established by reconstituting irradiated (C57BL/6 X DBA/2)F1 (B6D2F1) mice with Leu-Leu-OMe-treated C57BL/6 (B6) bone marrow and spleen cells. Spleen cells from such chimeras were found to have normal B and T cell mitogenic responses. Furthermore, levels of natural-killer cell function were comparable to those observed in B6----B6 syngeneic radiation chimeras established without Leu-Leu-OMe treatment of donor cells. Spleen cells from B6----B6D2F1 mice were identical with B6----B6 or B6 mice in allostimulatory capacity and thus contained no discernible cells of non-H-2b phenotype. Whereas B6----B6D2F1 spleen cells demonstrated alloproliferative and allocytotoxic responses toward H-2k bearing spleen cells, no H-2d specific proliferative or cytotoxic responses could be elicited. B6----B6D2F1 spleen cells did not suppress the generation of anti-H-2d or anti-H-2k proliferative or cytotoxic responses from control B6 spleen cells. Furthermore, addition of rat concanavalin A supernatants did not reconstitute anti-H-2d responses of B6----B6D2F1 chimeric spleen cells. Thus, Leu-Leu-OMe treatment of B6 donor cells not only prevents lethal graft-vs-host disease, but also permits establishment of long-lived parent----F1 chimeras that are selectively tolerant of host H-2 disparate alloantigens, but fully immunocompetent with respect to natural killer cell function, B and T cell mitogenesis, and anti-third party alloresponsiveness

  16. The phylogenetically-related pattern recognition receptors EFR and XA21 recruit similar immune signaling components in monocots and dicots.

    Nicholas Holton

    2015-01-01

    Full Text Available During plant immunity, surface-localized pattern recognition receptors (PRRs recognize pathogen-associated molecular patterns (PAMPs. The transfer of PRRs between plant species is a promising strategy for engineering broad-spectrum disease resistance. Thus, there is a great interest in understanding the mechanisms of PRR-mediated resistance across different plant species. Two well-characterized plant PRRs are the leucine-rich repeat receptor kinases (LRR-RKs EFR and XA21 from Arabidopsis thaliana (Arabidopsis and rice, respectively. Interestingly, despite being evolutionary distant, EFR and XA21 are phylogenetically closely related and are both members of the sub-family XII of LRR-RKs that contains numerous potential PRRs. Here, we compared the ability of these related PRRs to engage immune signaling across the monocots-dicots taxonomic divide. Using chimera between Arabidopsis EFR and rice XA21, we show that the kinase domain of the rice XA21 is functional in triggering elf18-induced signaling and quantitative immunity to the bacteria Pseudomonas syringae pv. tomato (Pto DC3000 and Agrobacterium tumefaciens in Arabidopsis. Furthermore, the EFR:XA21 chimera associates dynamically in a ligand-dependent manner with known components of the EFR complex. Conversely, EFR associates with Arabidopsis orthologues of rice XA21-interacting proteins, which appear to be involved in EFR-mediated signaling and immunity in Arabidopsis. Our work indicates the overall functional conservation of immune components acting downstream of distinct LRR-RK-type PRRs between monocots and dicots.

  17. Structural and functional characterization of human and murine C5a anaphylatoxins

    Schatz-Jakobsen, Janus Asbjørn; Yatime, Laure, E-mail: lay@mb.au.dk; Larsen, Casper [Aarhus University, Gustav Wieds Vej 10C, DK-8000 Aarhus (Denmark); Petersen, Steen Vang [Aarhus University, Bartholin Building, Wilhelm Meyers Allé 4, DK-8000 Aarhus (Denmark); Klos, Andreas [Medical School Hannover, Hannover (Germany); Andersen, Gregers Rom, E-mail: lay@mb.au.dk [Aarhus University, Gustav Wieds Vej 10C, DK-8000 Aarhus (Denmark)

    2014-06-01

    The structure of the human C5aR antagonist, C5a-A8, reveals a three-helix bundle conformation similar to that observed for human C5a-desArg, whereas murine C5a and C5a-desArg both form the canonical four-helix bundle. These conformational differences are discussed in light of the differential C5aR activation properties observed for the human and murine complement anaphylatoxins across species. Complement is an ancient part of the innate immune system that plays a pivotal role in protection against invading pathogens and helps to clear apoptotic and necrotic cells. Upon complement activation, a cascade of proteolytic events generates the complement effectors, including the anaphylatoxins C3a and C5a. Signalling through their cognate G-protein coupled receptors, C3aR and C5aR, leads to a wide range of biological events promoting inflammation at the site of complement activation. The function of anaphylatoxins is regulated by circulating carboxypeptidases that remove their C-terminal arginine residue, yielding C3a-desArg and C5a-desArg. Whereas human C3a and C3a-desArg adopt a canonical four-helix bundle fold, the conformation of human C5a-desArg has recently been described as a three-helix bundle. Here, the crystal structures of an antagonist version of human C5a, A8{sup Δ71–73}, and of murine C5a and C5a-desArg are reported. Whereas A8{sup Δ71–73} adopts a three-helix bundle conformation similar to human C5a-desArg, the two murine proteins form a four-helix bundle. A cell-based functional assay reveals that murine C5a-desArg, in contrast to its human counterpart, exerts the same level of activition as murine C5a on its cognate receptor. The role of the different C5a conformations is discussed in relation to the differential activation of C5a receptors across species.

  18. Glutamate receptors

    Kristensen, Anders S; Geballe, Matthew T; Snyder, James P;

    2006-01-01

    Fast excitatory synaptic transmission in the CNS relies almost entirely on the neurotransmitter glutamate and its family of ion channel receptors. An appreciation of the coupling between agonist binding and channel opening has advanced rapidly during the past five years, largely as a result of ne...

  19. Somatostatin receptors

    Møller, Lars Neisig; Stidsen, Carsten Enggaard; Hartmann, Bolette;

    2003-01-01

    In 1972, Brazeau et al. isolated somatostatin (somatotropin release-inhibiting factor, SRIF), a cyclic polypeptide with two biologically active isoforms (SRIF-14 and SRIF-28). This event prompted the successful quest for SRIF receptors. Then, nearly a quarter of a century later, it was announced...

  20. Netrin-1 Reduces Monocyte and Macrophage Chemotaxis towards the Complement Component C5a.

    Taylor, Lewis; Brodermann, Maximillian Hugo; McCaffary, David; Iqbal, Asif Jilani; Greaves, David R

    2016-01-01

    Netrin-1, acting at its cognate receptor UNC5b, has been previously demonstrated to inhibit CC chemokine-induced immune cell migration. In line with this, we found that netrin-1 was able to inhibit CCL2-induced migration of bone marrow derived macrophages (BMDMs). However, whether netrin-1 is capable of inhibiting chemotaxis to a broader range of chemoattractants remains largely unexplored. As our initial experiments demonstrated that RAW264.7 and BMDMs expressed high levels of C5a receptor 1 (C5aR1) on their surface, we aimed to determine the effect of netrin-1 exposure on monocyte/macrophage cell migration induced by C5a, a complement peptide that plays a major role in multiple inflammatory pathologies. Treatment of RAW264.7 macrophages, BMDMs and human monocytes with netrin-1 inhibited their chemotaxis towards C5a, as measured using two different real-time methods. This inhibitory effect was found to be dependent on netrin-1 receptor signalling, as an UNC5b blocking antibody was able to reverse netrin-1 inhibition of C5a induced BMDM migration. Treatment of BMDMs with netrin-1 had no effect on C5aR1 proximal signalling events, as surface C5aR1 expression, internalisation and intracellular Ca2+ release following C5aR1 ligation remained unaffected after netrin-1 exposure. We next examined receptor distal events that occur following C5aR1 activation, but found that netrin-1 was unable to inhibit C5a induced phosphorylation of ERK1/2, Akt and p38, pathways important for cellular migration. Furthermore, netrin-1 treatment had no effect on BMDM cytoskeletal rearrangement following C5a stimulation as determined by microscopy and real-time electrical impedance sensing. Taken together these data highlight that netrin-1 inhibits monocyte and macrophage cell migration, but that the mechanism behind this effect remains unresolved. Nevertheless, netrin-1 and its cognate receptors warrant further investigation as they may represent a potential avenue for the development of

  1. Streptococcal cell wall-induced arthritis and adjuvant arthritis in F344----Lewis and in Lewis----F344 bone marrow chimeras

    Streptococcal cell wall (SCW)-induced arthritis and adjuvant arthritis (AA) are rat models for chronic, erosive polyarthritis. Both models can be induced in susceptible Lewis rats, whereas F344 rats are resistant. In AA as well as in SCW arthritis, antigen-specific T lymphocytes have been demonstrated to be crucial for chronic disease. In this communication the authors describe their studies to probe the cellular mechanism responsible for the difference in susceptibility of Lewis and F344, using bone marrow chimeras. By transplanting bone marrow cells from F344 into lethally irradiated Lewis recipients, Lewis rats were rendered resistant to SCW arthritis induction. F344 rats reconstituted with Lewis bone marrow, i.e., Lewis----F344 chimeras, develop an arthritis upon SCW injection. For AA comparable results were obtained. These data suggest that both resistance and susceptibility to bacterium-induced chronic arthritis are mediated by hemopoietic/immune cells and that the recipiental environment does not influence the susceptibility to chronic joint inflammation

  2. Generation of anti-idiotype scFv for pharmacokinetic measurement in lymphoma patients treated with chimera anti-CD22 antibody SM03.

    Qi Zhao

    Full Text Available Pre-clinical and clinical studies of therapeutic antibodies require highly specific reagents to examine their immune responses, bio-distributions, immunogenicity, and pharmacodynamics in patients. Selective antigen-mimicking anti-idiotype antibody facilitates the assessment of therapeutic antibody in the detection, quantitation and characterization of antibody immune responses. Using mouse specific degenerate primer pairs and splenocytic RNA, we generated an idiotype antibody-immunized phage-displayed scFv library in which an anti-idiotype antibody against the therapeutic chimera anti-CD22 antibody SM03 was isolated. The anti-idiotype scFv recognized the idiotype of anti-CD22 antibody and inhibited binding of SM03 to CD22 on Raji cell surface. The anti-idiotype scFv was subsequently classified as Ab2γ type. Moreover, our results also demonstrated firstly that the anti-idiotype scFv could be used for pharmacokinetic measurement of circulating residual antibody in lymphoma patients treated with chimera anti-CD22 monoclonal antibody SM03. Of important, the present approach could be easily adopted to generate anti-idiotype antibodies for therapeutic antibodies targeting membrane proteins, saving the cost and time for producing a soluble antigen.

  3. Complement C5a-C5aR interaction enhances MAPK signaling pathway activities to mediate renal injury in trichloroethylene sensitized BALB/c mice.

    Zhang, Jia-xiang; Zha, Wan-sheng; Ye, Liang-ping; Wang, Feng; Wang, Hui; Shen, Tong; Wu, Chang-hao; Zhu, Qi-xing

    2016-02-01

    We have previously shown complement activation as a possible mechanism for trichloroethylene (TCE) sensitization, leading to multi-organ damage including the kidneys. In particular, excessive deposition of C5 and C5b-9-the membrane attack complex, which can generate significant tissue damage, was observed in the kidney tissue after TCE sensitization. The present study tested the hypothesis that anaphylatoxin C5a binding to its receptor C5aR mediates renal injury in TCE-sensitized BALB/c mice. BALB/c mice were sensitized through skin challenge with TCE, with or without pretreatment by the C5aR antagonist W54011. Kidney histopathology and the renal functional test were performed to assess renal injury, and immunohistochemistry and fluorescent labeling were carried out to assess C5a and C5aR expressions. TCE sensitization up-regulated C5a and C5aR expressions in kidney tissue, generated inflammatory infiltration, renal tubule damage, glomerular hypercellularity and impaired renal function. Antagonist pretreatment blocked C5a binding to C5aR and attenuated TCE-induced tissue damage and renal dysfunction. TCE sensitization also caused the deposition of major pro-inflammatory cytokines IL-2, TNF-α and IFN-γ in the kidney tissue (P TCE sensitization-induced increase of IL-2, TNF-α and IFN-γ (P TCE or other environmental chemicals. PMID:26095957

  4. Daphnia HR96 is a promiscuous xenobiotic and endobiotic nuclear receptor

    Karimullina, Elina [Environmental Toxicology Program, Clemson University, Clemson, SC 29634 (United States); Institute of Plant and Animal Ecology, Russian Academy of Sciences, Ural Branch, Yekaterinburg 620144 (Russian Federation); Li Yangchun; Ginjupalli, Gautam K. [Environmental Toxicology Program, Clemson University, Clemson, SC 29634 (United States); Baldwin, William S., E-mail: baldwin@clemson.edu [Environmental Toxicology Program, Clemson University, Clemson, SC 29634 (United States); Biological Sciences, Clemson University, Clemson, SC (United States)

    2012-07-15

    Daphnia pulex is the first crustacean to have its genome sequenced. The genome project provides new insight and data into how an aquatic crustacean may respond to environmental stressors, including toxicants. We cloned Daphnia pulex HR96 (DappuHR96), a nuclear receptor orthologous to the CAR/PXR/VDR group of nuclear receptors. In Drosophila melanogaster, (hormone receptor 96) HR96 responds to phenobarbital exposure and has been hypothesized as a toxicant receptor. Therefore, we set up a transactivation assay to test whether DappuHR96 is a promiscuous receptor activated by xenobiotics and endobiotics similar to the constitutive androstane receptor (CAR) and the pregnane X-receptor (PXR). Transactivation assays performed with a GAL4-HR96 chimera demonstrate that HR96 is a promiscuous toxicant receptor activated by a diverse set of chemicals such as pesticides, hormones, and fatty acids. Several environmental toxicants activate HR96 including estradiol, pyriproxyfen, chlorpyrifos, atrazine, and methane arsonate. We also observed repression of HR96 activity by chemicals such as triclosan, androstanol, and fluoxetine. Nearly 50% of the chemicals tested activated or inhibited HR96. Interestingly, unsaturated fatty acids were common activators or inhibitors of HR96 activity, indicating a link between diet and toxicant response. The omega-6 and omega-9 unsaturated fatty acids linoleic and oleic acid activated HR96, but the omega-3 unsaturated fatty acids alpha-linolenic acid and docosahexaenoic acid inhibited HR96, suggesting that these two distinct sets of lipids perform opposing roles in Daphnia physiology. This also provides a putative mechanism by which the ratio of dietary unsaturated fats may affect the ability of an organism to respond to a toxic insult. In summary, HR96 is a promiscuous nuclear receptor activated by numerous endo- and xenobiotics.

  5. Daphnia HR96 is a promiscuous xenobiotic and endobiotic nuclear receptor

    Daphnia pulex is the first crustacean to have its genome sequenced. The genome project provides new insight and data into how an aquatic crustacean may respond to environmental stressors, including toxicants. We cloned Daphnia pulex HR96 (DappuHR96), a nuclear receptor orthologous to the CAR/PXR/VDR group of nuclear receptors. In Drosophila melanogaster, (hormone receptor 96) HR96 responds to phenobarbital exposure and has been hypothesized as a toxicant receptor. Therefore, we set up a transactivation assay to test whether DappuHR96 is a promiscuous receptor activated by xenobiotics and endobiotics similar to the constitutive androstane receptor (CAR) and the pregnane X-receptor (PXR). Transactivation assays performed with a GAL4-HR96 chimera demonstrate that HR96 is a promiscuous toxicant receptor activated by a diverse set of chemicals such as pesticides, hormones, and fatty acids. Several environmental toxicants activate HR96 including estradiol, pyriproxyfen, chlorpyrifos, atrazine, and methane arsonate. We also observed repression of HR96 activity by chemicals such as triclosan, androstanol, and fluoxetine. Nearly 50% of the chemicals tested activated or inhibited HR96. Interestingly, unsaturated fatty acids were common activators or inhibitors of HR96 activity, indicating a link between diet and toxicant response. The omega-6 and omega-9 unsaturated fatty acids linoleic and oleic acid activated HR96, but the omega-3 unsaturated fatty acids alpha-linolenic acid and docosahexaenoic acid inhibited HR96, suggesting that these two distinct sets of lipids perform opposing roles in Daphnia physiology. This also provides a putative mechanism by which the ratio of dietary unsaturated fats may affect the ability of an organism to respond to a toxic insult. In summary, HR96 is a promiscuous nuclear receptor activated by numerous endo- and xenobiotics.

  6. 解偶联蛋白嵌合体及突变体的构建方法%Construction of chimeras and mutations for uncoupling proteins

    王超; 刘洋; 段秀梅; 田庄; 王银萍; 沃夫冈·格莱尔; 付彤

    2013-01-01

    Objective To construct uncoupling proteins (UCPs) chimeras and mutations and provide conditions for study on the functional domains of uncoupling protein family. Methods The gene fragments of UCPs chimera were obtained by routine polymerase chain reaction (PCR) and splicing overlap extension PCR (SOE-PCR). Then these sequences were respectively cloned into the vector of pCR2. 1 and sequenced. The recombinant eukaryotic expression plasmid pcDNA3. 1 containing UCPs chimera was constructed by restrictive enzyme ligation. The recombinant plasmid of pcDNAUCPlUCP2 , pcDNAUCP2ucpl and pcDNAUCP3ucpl were identified by PCR and restrictive enzyme digestion. The mutations of pcDNA-UCP3R167G/pcDNA- UCP3RE171/172GG were generated by site-directed mutagenesis and then verified by sequencing. Results The identification of target gene by restrictve enzyme and PCR was the same as expectation. The sequence of chimera gene was completely identical with the expectation device. Conclusion The recombinant eukaryotic expression plasmid containing UCPs chimeras and mutations is constructed successfully.%目的:构建解偶联蛋白(UCPs)嵌合体和突变体,为阐明解偶联蛋白家族功能结构域的研究提供条件.方法:采用普通PCR和重叠延伸PCR获得UCPs嵌合体基因片段,分别插入pCR2.1测序载体后进行测序,再以限制性内切酶连接方式将嵌合基因定向亚克隆到真核表达质粒pcDNA3.1中,获得pcDNAUCP1UCP2、pcDNAUCP2UCP1和pcDNAUCP3UCP1,以PCR和酶切方法鉴定构建的重组真核表达质粒pcDNA.利用定向点突变产生pcDNA-UCP3R167G/pcDNA-UCP3RE171/172GG,并进行测序证实.结果:PCR和酶切,获得的目的基因与嵌合基因片段中包含的碱基数量吻合;测序结果,UCPs嵌合体基因序列、突变体基因序列与预期设计完全相同.结论:成功地构建了含有UCPs嵌合体和突变体基因重组真核表达质粒.

  7. Towards the development of a chimera-free in vitro induced mutagenesis system in cassava (Manihot esculenta, Crantz)

    Cassava, an herbaceous plant with starchy storage roots, has the potentials for being the cheapest source of starch for varied industries. To achieve this, the starch types must be clearly discriminated into either high preponderance of amylose or the other extreme of amylopectin content (waxy starch). Being a vegetative propagated crop with major crossing barriers, induced mutagenesis holds promise for modifying the starch characteristics of this crop. The efficiency of induced mutagenesis in a vegetative propagated crop such as cassava is severely limited by the occurrence of chimeras. To ameliorate this, the induced mutagenesis strategy must permit the regeneration of plants from one or a few cells that have been induced to mutate. We report the optimisation of protocols for the generation of plantlets from somatic embryos that were exposed to EMS. Different explants (buds and somatic embryos) of a cassava clone with high starch content were exposed to different doses (concentration and duration) of ethylmethane sulfonate (EMS) with the aim of determining the optimal doses for generating induced mutants. A wide range of reactions to EMS, from slightly reduced plantlet regeneration to lethality, was observed leading to the determination of the optimum exposure treatment. The regenerated plantlets were transplanted to pots in the greenhouse for hardening and later transferred to the field. In order to achieve homozygousity of the mutation events, the putative mutants were selfed- crosses. The immature embryos were rescued (cultured on aseptic growth media) in order to speed-up the process of generating the mutant population as well as avoid the possibility of embryo abortion. The resulting plantlets were again subsequently hardened and transferred to the field. Currently, 610 plants, constituting the putative mutant population have been established in the field in Palmira, Colombia. As a pilot assay, this work has demonstrated the feasibility of combining EMS

  8. Effects of T cell depletion in radiation bone marrow chimeras. II. Requirement for allogeneic T cells in the reconstituting bone marrow inoculum for subsequent resistance to breaking of tolerance

    The ability of normal recipient-type lymphocytes to break tolerance in long-term allogenic radiation chimeras has been investigated. Reconstitution of lethally irradiated mice with a mixture of syngeneic and allogeneic T cell-depleted (TCD) bone marrow (BM) has previously been shown to lead to mixed chimerism and permanent, specific tolerance to donor and host alloantigen (3-5). If allogeneic T cells are not depleted from the reconstituting inoculum, complete allogeneic chimerism results; however, no clinical evidence for GVHD is observed, presumably due to the protective effect provided by syngeneic TCD BM. This model has now been used to study the effects of allogenic T cells administered in reconstituting BM inocula on stability of long-term tolerance. We have attempted to break tolerance in long-term chimeras originally reconstituted with TCD or non-TCD BM by challenging them with inocula containing normal, nontolerant recipient strain lymphocytes. tolerance was broken with remarkable ease in recipients of mixed marrow inocula in which both original BM components were TCD. In contrast, tolerance in chimeras originally reconstituted with non-TCD allogeneic BM was not affected by such inocula. Susceptibility to loss of chimerism and tolerance was not related to initial levels of chimerism per se, but rather to T cell depletion of allogeneic BM, since chimeras reconstituted with TCD allogeneic BM alone (mean level of allogeneic chimerism 98%) were as susceptible as mixed chimeras to the tolerance-breaking effects of such inocula. The possible contribution of GVH reactivity to this resistance was investigated using an F1 into parent strain combination. In these animals, the use of non-TCD F1 BM inocula for reconstitution did not lead to resistance to the tolerance-breaking effects of recipient strain splenocytes

  9. DNAzyme-mediated recovery of small recombinant RNAs from a 5S rRNA-derived chimera expressed in Escherichia coli

    Willson Richard C

    2010-12-01

    Full Text Available Abstract Background Manufacturing large quantities of recombinant RNAs by overexpression in a bacterial host is hampered by their instability in intracellular environment. To overcome this problem, an RNA of interest can be fused into a stable bacterial RNA for the resulting chimeric construct to accumulate in the cytoplasm to a sufficiently high level. Being supplemented with cost-effective procedures for isolation of the chimera from cells and recovery of the recombinant RNA from stabilizing scaffold, this strategy might become a viable alternative to the existing methods of chemical or enzymatic RNA synthesis. Results Sequence encoding a 71-nucleotide recombinant RNA was inserted into a plasmid-borne deletion mutant of the Vibrio proteolyticus 5S rRNA gene in place of helix III - loop C segment of the original 5S rRNA. After transformation into Escherichia coli, the chimeric RNA (3×pen aRNA was expressed constitutively from E. coli rrnB P1 and P2 promoters. The RNA chimera accumulated to levels that exceeded those of the host's 5S rRNA. A novel method relying on liquid-solid partitioning of cellular constituents was developed for isolation of total RNA from bacterial cells. This protocol avoids toxic chemicals, and is therefore more suitable for large scale RNA purification than traditional methods. A pair of biotinylated 8-17 DNAzymes was used to bring about the quantitative excision of the 71-nt recombinant RNA from the chimera. The recombinant RNA was isolated by sequence-specific capture on beads with immobilized complementary deoxyoligonucleotide, while DNAzymes were recovered by biotin affinity chromatography for reuse. Conclusions The feasibility of a fermentation-based approach for manufacturing large quantities of small RNAs in vivo using a "5S rRNA scaffold" strategy is demonstrated. The approach provides a route towards an economical method for the large-scale production of small RNAs including shRNAs, siRNAs and aptamers for use

  10. The synthesis and expression of a gene for the complement factor C5a

    A gene coding for the 74 amino acid human complement factor C5a has been chemically synthesized, cloned and expressed in E. coli. The 253 base-pair fragment was constructed from 16 oligodeoxyribonucleotides using the phosphoramidite chemistry. It was assembled in two steps: the assembly of three sub-fragments from the oligonucleotides and the final assembly from the three subfragments. The gene was cloned into a pBR322 derived plasmid containing the lac UV5-D up-promoter mutation. Expression was quanitified by immunoassay and by measuring competition for binding of human 125labelled C5a to the receptors on polymorphonuclear leukocytes. The C5a now being obtained possesses a 40-fold higher specific activity (C5atotal protein) than C5a from complement-activated human serum. This should avoid the problem of contamination of intact C5a with the des-Arg form of the molecule found in serum

  11. Chimeras: an ethical consideration

    H.J.G. Zandman

    2011-07-01

    Full Text Available Scientists have started with experimentation that raises difficult ethical questions. It comprises taking material from the human blueprint (DNA and inserting this in various test animals. The purpose of such research is noble, namely the alleviation of hu- man suffering. Yet the ethical ramifications of blending the hu- man and animal genome are significant, especially for Chris- tians. The creation of all living entities after their kind and the image-bearing dignity attributed to man both come under se- vere ethical stress for those who presuppose divine order in God’s ecology.  For non-Christians the philosophical dilemma ought not to exist in the ethical sense if applied at the purest level. If the human is merely a kind of animal, along with and ontologically not diffe- rent from other animals, there is little logical reason to object to chimeric research apart from a concern about what such re- search and application might do to the order of life pragmati- cally. However, many non-Christian do object. Man is made in God’s image and the concept of human dignity and a universal sense of right and wrong still binds Christians and non-Chris- tians when considering ethics in the field of chimeric research. As the mixing of human stem cells with embryonic animals takes place, certain non-Christian authors protest that human dignity is being diminished and the animal essence is being vio- lated.

  12. Empathy: The Charismatic Chimera.

    Macarov, David

    1978-01-01

    Three major meanings of "empathy" are discussed with reference to the widespread imprecision in its use. It is suggested that undifferentiated use of the term in social work education is dangerous, particularly in view of the positive valence associated with being empathetic. (Author/BH)

  13. Continua or Chimera?

    Booth, Tony

    1994-01-01

    This article looks at two concepts in the British 1993 draft Code of Practice concerning students with special needs: the concepts of a "continuum of needs" and a "continuum of provision." Issues involved in connecting the two continua are addressed, including whether service delivery decisions should be based on severity of need or according to…

  14. Phrenoblysis: Real or Chimera?

    Marsh, R. W.

    1985-01-01

    Epstein (1974) claims evidence for regular two-year growth spurts in the development of brain and mind, a phenomenon he calls phrenoblysis. Unfortunately, repeated analysis of the data he presents as proof of his theory provides no support. (Author/RH)

  15. The Chimera of Validity

    Baker, Eva L.

    2013-01-01

    Background/Context: Education policy over the past 40 years has focused on the importance of accountability in school improvement. Although much of the scholarly discourse around testing and assessment is technical and statistical, understanding of validity by a non-specialist audience is essential as long as test results drive our educational…

  16. The Chimera of Professionalism.

    Nelson, Bonnie R.

    1980-01-01

    Much of what passes for professionalism is self-serving elitism and not relevant to librarianship. Librarians, most of whom are women, should continue to improve service to the public and strive by pragmatic means to overcome low pay and status. (RAA)

  17. PNA Peptide chimerae

    Koch, T.; Næsby, M.; Wittung, P.; Jørgensen, M.; Larsson, C.; Buchardt, O.; Stanly, C.J.; Norden, B.; Nielsen, P.E.; Ørum, H.

    1995-01-01

    Radioactive labelling of PNA has been performed try linking a peptide segment to the PNA which is substrate for protein kinase A. The enzymatic phosphorylation proceeds in almost quantitative yields.......Radioactive labelling of PNA has been performed try linking a peptide segment to the PNA which is substrate for protein kinase A. The enzymatic phosphorylation proceeds in almost quantitative yields....

  18. PNA Peptide chimerae

    Koch, T.; Næsby, M.; Wittung, P.;

    1995-01-01

    Radioactive labelling of PNA has been performed try linking a peptide segment to the PNA which is substrate for protein kinase A. The enzymatic phosphorylation proceeds in almost quantitative yields....

  19. An amino acid residue in the second extracellular loop determines the agonist-dependent tolerance property of the human D3 dopamine receptor.

    Gil-Mast, Sara; Kortagere, Sandhya; Kota, Kokila; Kuzhikandathil, Eldo V

    2013-06-19

    The D3 dopamine receptor is a therapeutic target for treating various nervous system disorders such as schizophrenia, Parkinson's disease, depression, and addictive behaviors. The crystal structure of the D3 receptor bound to an antagonist was recently described; however, the structural features that contribute to agonist-induced conformational changes and signaling properties are not well understood. We have previously described the conformation-dependent tolerance and slow response termination (SRT) signaling properties of the D3 receptor and identified the C147 residue in the second intracellular loop (IL2) of the D3 receptor as important for the tolerance property. Interestingly, while IL2 and the C147 residue, in particular, were important for dopamine- and quinpirole-induced tolerance, this residue did not affect the severe tolerance induced by the high affinity, D3 receptor-selective agonist, PD128907. Here, we used D2/D3 receptor chimeras and site-specific D3 receptor mutants to identify another residue, D187, in the second extracellular loop (EC2) of the human D3 receptor that mediates the tolerance property induced by PD128907, quinpirole, pramipexole, and dopamine. Molecular dynamics simulations confirmed the distinct conformation adopted by D3 receptor during tolerance and suggested that in the tolerant D3 receptor the D187 residue in EC2 forms a salt bridge with the H354 residue in EC3. Indeed, site-directed mutation of the H354 residue resulted in loss of PD1287907-induced tolerance. The mapping of specific amino acid residues that contribute to agonist-dependent conformation changes and D3 receptor signaling properties refines the agonist-bound D3 receptor pharmacophore model which will help develop novel D3 receptor agonists. PMID:23477444

  20. Site- and bond-percolation thresholds in Kn ,n-based lattices: Vulnerability of quantum annealers to random qubit and coupler failures on chimera topologies

    Melchert, O.; Katzgraber, Helmut G.; Novotny, M. A.

    2016-04-01

    We estimate the critical thresholds of bond and site percolation on nonplanar, effectively two-dimensional graphs with chimeralike topology. The building blocks of these graphs are complete and symmetric bipartite subgraphs of size 2 n , referred to as Kn ,n graphs. For the numerical simulations we use an efficient union-find-based algorithm and employ a finite-size scaling analysis to obtain the critical properties for both bond and site percolation. We report the respective percolation thresholds for different sizes of the bipartite subgraph and verify that the associated universality class is that of standard two-dimensional percolation. For the canonical chimera graph used in the D-Wave Systems Inc. quantum annealer (n =4 ), we discuss device failure in terms of network vulnerability, i.e., we determine the critical fraction of qubits and couplers that can be absent due to random failures prior to losing large-scale connectivity throughout the device.