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Sample records for marrow chimeras endothelial

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

    International Nuclear Information System (INIS)

    Hinrichs, D.J.; Wegmann, K.W.; Dietsch, G.N.

    1987-01-01

    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

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

    International Nuclear Information System (INIS)

    McCarthy, S.A.; Griffith, I.J.; Gambel, P.; Francescutti, L.H.; Wegmann, T.G.

    1985-01-01

    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

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

    International Nuclear Information System (INIS)

    Auchincloss, H. Jr.; Sachs, D.H.

    1983-01-01

    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

  4. Dominance and persistence of donor marrow in long-lived allogeneic radiation chimeras obtained with unmanipulated bone marrow

    International Nuclear Information System (INIS)

    Pierpaoli, W.; Maestroni, G.J.M.

    1983-01-01

    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.)

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

    International Nuclear Information System (INIS)

    Sharrow, S.O.; Mathieson, B.J.; Singer, A.

    1981-01-01

    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

  6. Mechanism of donor to host tolerance in rat bone marrow chimeras

    International Nuclear Information System (INIS)

    Tutschka, P.; Schwerdtfeger, R.; Slavin, R.; Santos, G.

    1977-01-01

    Lewis rats were conditioned with cyclophosphamide and grafted with AgB incompatible bone marrow. They were examined 250 days after transplantation and demonstrated to be healthy complete chimeras. Marrow cells from these chimeras were infused into lethally irradiated ACI, Lewis and BN recipients. Graft-versus-host disease occurred only in the BN rats. Other chimeric rats were given no treatment, busulfan, CY, or total body irradiation prior to the infusion of normal ACI BM. GvHD occurred only in animals given CY or TBI. Normal Lewis rats were conditioned with TBI and given ACI BM. In addition, they received whole blood, irradiated blood, or serum from chimeric rats. GvHD developed in all animals except those given unirradiated chimeric blood. These studies suggest that suppressor cell populations, sensitive to immunosuppression, are likely the fundamental mechanism of recovery from GvHD

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

    International Nuclear Information System (INIS)

    Sharrow, S.O.; Singer, A.; Hammerling, U.; Mathieson, B.J.

    1983-01-01

    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

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

    International Nuclear Information System (INIS)

    Onoe, K.; Good, R.A.; Yamamoto, K.

    1986-01-01

    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

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

    International Nuclear Information System (INIS)

    Auchincloss, H. Jr.; Sachs, D.H.

    1983-01-01

    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

  10. white leghorn chimeras based on bone marrow mesenchymal stem

    African Journals Online (AJOL)

    stem cells (BMMSCs), and to assess its immune tolerance based on variations in proportion of ... Keywords: Bone marrow mesenchymal stem cells, Immune tolerance, ... in tissue injury, transplantation, and ..... 0.05, **p < 0.01; (b) expression of the duck gene in different organs .... CD30hi Marek's disease lymphoma cell.

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

    International Nuclear Information System (INIS)

    Yasumizu, R.; Onoe, K.; Iwabuchi, K.; Ogasawara, M.; Fujita, M.; Okuyama, H.; Good, R.A.; Morikawa, K.

    1985-01-01

    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

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

    International Nuclear Information System (INIS)

    Tutschka, P.J.; Ki, P.F.; Beschorner, W.E.; Hess, A.D.; Santos, G.W.

    1981-01-01

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

    International Nuclear Information System (INIS)

    Tutschka, P.J.; Ki, P.F.; Beschorner, W.E.; Hess, A.D.; Santos, G.W.

    1981-01-01

    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

  14. Production of somatic chimera chicks by injection of bone marrow cells into recipient blastoderms.

    Science.gov (United States)

    Heo, Young Tae; Lee, Sung Ho; Kim, Teoan; Kim, Nam Hyung; Lee, Hoon Taek

    2012-01-01

    Several types of cells, including blastoderm cells, primordial germ cells, and embryonic germ cells were injected into early-stage recipient embryos to produce chimera avians and to gain insights into cell development. However, a limited number of studies of avian adult stem cells have also been conducted. This study is, to the best of our knowledge, the first to evaluate chicken bone marrow cells' (chBMC) ability to differentiate into multiple cell lineages and capability to generate chimera chicks. We induced random differentiation of chBMCs in vitro and injected immunologically selected pluripotent cells in chBMCs into the blastoderms of recipient eggs. The multipotency of BMCs from the barred Plymouth rock (BPR) was confirmed via AP staining, RT-PCR, immunocytochemistry, and FACS using specific markers, such as Oct-4 and SSEA-1, 3 and 4. Isolated chBMCs were found to be able to induce in vitro differentiation to multiple cell lineages. Approximately 5,000 chBMCs were injected into the blastoderms of white leghorn (WL) recipients and proved able to contribute to the generation of somatic chimera chicks with a frequency of 2.7% (2 of 73). Confirmation of chimerism in hatched chicks was achieved via PCR analysis using D-loop-specific primers of BPR and WL. Our study demonstrated the successful production of chimera chicks using chBMC. Therefore, we propose that the use of adult chBMCs may constitute a new possible approach to the production of chimera poultry, and may provide helpful studies in avian developmental biology.

  15. Characterization of hemopoietic stem cell chimerism in antibody-facilitated bone marrow chimeras

    International Nuclear Information System (INIS)

    Francescutti, L.H.; Gambel, P.; Wegmann, T.G.

    1985-01-01

    The authors have previously described a model for bone marrow transplantation that involves preparation of the host with monoclonal antibody against class I or class II antigens instead of irradiation or cytotoxic drugs. This allows engraftment and subsequent repopulation of the host by donor tissue. They have previously reported on chimerism in the peripheral blood of P1----(P1 X P2)F1 animals. In this report, the authors describe the examination of the bone marrow and spleen stem cell chimerism of these antibody-facilitated (AF) chimeras, by determining, with an isozyme assay, the phenotype of methylcellulose colonies grown from stem cells. They have found a correlation between peripheral blood chimerism and the stem cell constitution of both spleen and bone marrow. The peripheral blood chimerism also correlates with the level of chimerism in macrophages derived from peritoneal exudate cells. These findings indicate that assaying the peripheral blood of such chimeras provides an excellent indication of the degree of chimerism at the stem cell level and stands in sharp contrast to the level of chimerism in certain lymphoid compartments

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

    International Nuclear Information System (INIS)

    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 infection with this parasite is expressed through bone-marrow-derived cells

  17. The determination of lymphoid cell chimerism using peripheral blood lymphocytes from murine bone marrow chimeras

    International Nuclear Information System (INIS)

    Skidmore, B.J.; Miller, L.S.

    1978-01-01

    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 10 5 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.)

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

    International Nuclear Information System (INIS)

    Vriesendorp, H.M.

    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 10 8 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.)

  19. Bone marrow cells from allogeneic bone marrow chimeras inhibit the generation of cytotoxic lymphocyte responses against both donor and recipient cells

    International Nuclear Information System (INIS)

    Ogasawara, M.; Iwabuchi, K.; Good, R.A.; Onoe, K.

    1988-01-01

    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. Double-chimera proteins to enhance recruitment of endothelial cells and their progenitor cells.

    Science.gov (United States)

    Behjati, M; Kazemi, M; Hashemi, M; Zarkesh-Esfahanai, S H; Bahrami, E; Hashemi-Beni, B; Ahmadi, R

    2013-08-20

    Enhanced attraction of selective vascular reparative cells is of great importance in order to increase vascular patency after endovascular treatments. We aimed to evaluate efficient attachment of endothelial cells and their progenitors on surfaces coated with mixture of specific antibodies, L-selectin and VE-cadherin, with prohibited platelet attachment. The most efficient conditions for coating of L-selectin-Fc chimera and VE-cadherin-Fc chimera proteins were first determined by protein coating on ELISA plates. The whole processes were repeated on titanium substrates, which are commonly used to coat stents. Endothelial progenitor cells (EPCs) and human umbilical vein endothelial cells (HUVECs) were isolated and characterized by flow cytometry. Cell attachment, growth, proliferation, viability and surface cytotoxicity were evaluated using nuclear staining and MTT assay. Platelet and cell attachment were evaluated using scanning electron microscopy. Optimal concentration of each protein for surface coating was 50 ng/ml. The efficacy of protein coating was both heat and pH independent. Calcium ions had significant impact on simultaneous dual-protein coating (P<0.05). Coating stability data revealed more than one year stability for these coated proteins at 4°C. L-selectin and VE-cadherin (ratio of 50:50) coated surface showed highest EPC and HUVEC attachment, viability and proliferation compared to single protein coated and non-coated titanium surfaces (P<0.05). This double coated surface did not show any cytotoxic effect. Surfaces coated with L-selectin and VE-cadherin are friendly surface for EPC and endothelial cell attachment with less platelet attachment. These desirable factors make the L-selectin and VE-cadherin coated surfaces perfect candidate endovascular device. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

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

    International Nuclear Information System (INIS)

    Duprez, V.; Maziarz, R.; Weinberger, O.; Burakoff, S.J.

    1984-01-01

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

    International Nuclear Information System (INIS)

    Yu, J.C.; Webster, M.; Fox, I.J.

    1990-01-01

    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

  3. Macrophage function in murine allogeneic bone marrow radiation chimeras in the early phase after transplantation

    International Nuclear Information System (INIS)

    Roesler, J.; Baccarini, M.; Vogt, B.; Lohmann-Matthes, M.L.

    1989-01-01

    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

  4. Restricted antibody formation to sheep erythrocytes of allogeneic bone marrow chimeras histoincompatible at the K end of the H-2 complex

    International Nuclear Information System (INIS)

    Onoe, K.; Yasumizu, R.; Oh-Ishi, T.; Kakinuma, M.; Good, R.A.; Morikawa, K.

    1981-01-01

    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. Characterization of vascular endothelial progenitor cells from chicken bone marrow

    Directory of Open Access Journals (Sweden)

    Bai Chunyu

    2012-05-01

    Full Text Available Abstract Background Endothelial progenitor cells (EPC are a type of stem cell used in the treatment of atherosclerosis, vascular injury and regeneration. At present, most of the EPCs studied are from human and mouse, whereas the study of poultry-derived EPCs has rarely been reported. In the present study, chicken bone marrow-derived EPCs were isolated and studied at the cellular level using immunofluorescence and RT-PCR. Results We found that the majority of chicken EPCs were spindle shaped. The growth-curves of chicken EPCs at passages (P 1, -5 and -9 were typically “S”-shaped. The viability of chicken EPCs, before and after cryopreservation was 92.2% and 81.1%, respectively. Thus, cryopreservation had no obvious effects on the viability of chicken EPCs. Dil-ac-LDL and FITC-UAE-1 uptake assays and immunofluorescent detection of the cell surface markers CD34, CD133, VEGFR-2 confirmed that the cells obtained in vitro were EPCs. Observation of endothelial-specific Weibel-Palade bodies using transmission electron microscopy further confirmed that the cells were of endothelial lineage. In addition, chicken EPCs differentiated into endothelial cells and smooth muscle cells upon induction with VEGF and PDGF-BB, respectively, suggesting that the chicken EPCs retained multipotency in vitro. Conclusions These results suggest that chicken EPCs not only have strong self-renewal capacity, but also the potential to differentiate into endothelial and smooth muscle cells. This research provides theoretical basis and experimental evidence for potential therapeutic application of endothelial progenitor cells in the treatment of atherosclerosis, vascular injury and diabetic complications.

  6. Immunohistochemical localization of host and donor-derived cells in the regenerating thymus of radiation bone marrow chimeras

    International Nuclear Information System (INIS)

    Ceredig, R.; Schreyer, M.

    1984-01-01

    The anatomical distribution of CBA (Thy-1.2) host and AKR (Thy-1.1) donor-derived cells in the regenerating thymus of AKR → CBA radiation bone marrow chimeras was investigated. Cryostat sections of chimeric thymuses were incubated with biotin-conjugated monoclonal anti-Thy-1 antibodies specific for host and donor-derived cells and the distribution of the corresponding Thy-1 antigen revealed by the immunoperoxidase staining technique. The thymus was initially repopulated by Thy-1.2 + host-derived cells, but by 28 days following bone marrow reconstitution the few remaining host cells were found mostly in the thymus medulla. However, occasional Thy-1.2 + cells were still present in extramedullary, primarily cortical, sites. Donor-derived (Thy-1.1 + ) cells were first seen in the 11-day chimeric thymus as single cells frequently closely associated with blood vessels in medullary areas. By 17 days, the cortex contained many Thy-1.1 + cells, although occasional single positive cells were still present in the medulla. Changes in the anatomical distribution of host and donor-derived cells in the regenerating chimeric thymus appeared to correlate with changes in their Thy-1 fluorescence profile as determined by flow microfluorometry. (Auth.)

  7. Growth of transplantable melanoma and leukaemia and prevention of virus-induced leukaemia in long lived radiation chimeras constructed with unmanipulated bone marrow

    International Nuclear Information System (INIS)

    Pierpaoli, W.

    1985-01-01

    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)

  8. Contrasting feature in the repopulation of host-type T cells in the spleens of F1----P and P----F1 radiation bone marrow chimeras

    International Nuclear Information System (INIS)

    Hirokawa, K.; Sado, T.; Kubo, S.; Kamisaku, H.; Utsuyama, M.

    1986-01-01

    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

  9. Bone marrow endothelial progenitors in atherosclerotic plaque resolution

    Science.gov (United States)

    Yao, Longbiao; Heuser-Baker, Janet; Herlea-Pana, Oana; Barlic-Dicen, Jana

    2013-01-01

    Atherosclerosis is a major cause of morbidity and mortality in the United States. Persistently elevated circulating low-density lipoprotein, or hypercholesterolemia, and deposition of low-density lipoprotein in the vascular wall are the main inducers of atherosclerosis, which manifests itself as arterial lesions or plaques. Some plaques become thrombosis-prone and rupture, causing acute myocardial infarction or stroke. Lowering plasma cholesterol through the use of statins is the primary intervention against atherosclerosis. Treatment with statins slows progression of atherosclerosis but can only support limited plaque regression. Partially regressed plaques continue to pose a serious threat due to their remaining potential to rupture. Thus, new interventions inducing complete reversal of atherosclerosis are being sought. Implementation of new therapies will require clear understanding of the mechanisms driving plaque resolution. In this Commentary, we highlight the role of bone marrow endothelial progenitors in atherosclerotic plaque regression and discuss how regenerative cell-based interventions could be used in combination with plasma lipid-lowering to induce plaque reversal in order to prevent and/or reduce adverse cardiovascular events. PMID:23538778

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

    International Nuclear Information System (INIS)

    Mosley, R.L.; Styre, D.; Klein, J.R.

    1990-01-01

    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

  11. 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

    International Nuclear Information System (INIS)

    Sykes, M.; Sheard, M.A.; Sachs, D.H.

    1988-01-01

    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

  12. H-2-incompatible bone marrow chimeras produce donor-H-2-restricted Ly-2 suppressor T-cell factor(s)

    International Nuclear Information System (INIS)

    Noguchi, M.; Onoe, K.; Ogasawara, M.; Iwabuchi, K.; Geng, L.; Ogasawara, K.; Good, R.A.; Morikawa, K.

    1985-01-01

    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

  13. Streptococcal cell wall-induced arthritis and adjuvant arthritis in F344----Lewis and in Lewis----F344 bone marrow chimeras

    International Nuclear Information System (INIS)

    van Bruggen, M.C.; van den Broek, M.F.; van den Berg, W.B.

    1991-01-01

    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

  14. Efficient natural defense mechanisms against Listeria monocytogenes in T and B cell-deficient allogeneic bone marrow radiation chimeras. Preactivated macrophages are the main effector cells in an early phase after bone marrow transfer

    International Nuclear Information System (INIS)

    Roesler, J.; Groettrup, E.B.; Baccarini, M.; Lohmann-Mattes, M.L.

    1989-01-01

    Radiation chimeras in the early phase after bone marrow transplantation are a good model to study the efficiency of the body's nonspecific defense system represented by macrophages (M phi), polymorphonuclear cells (PMN), and NK cells. These cell types are present in large numbers in spleen and liver at that time, whereas the specific immune system represented by T and B cells is functionally deficient. We previously reported enhanced activities in vitro of M phi (and PMN) from recipient animals in an early phase after allogeneic bone marrow transfer. We here demonstrate that these activities result in enhanced spontaneous resistance against Listeria monocytogenes in vivo: CFU of L. monocytogenes in spleen and liver 48 h after infection were about 1 or 2 to 4 log steps less than in untreated control mice of donor or host haplotype. This enhanced resistance decreased over the 4-mo period after marrow transfer. Preactivated M phi were identified as the most important effector cells. Isolated from spleen and peritoneal cavity, they performed enhanced killing of phagocytosed Listeria. Such preactivated M phi occurred in recipient animals after transfer of allogeneic but not of syngeneic bone marrow. The precise mechanism of M phi activation in the allogeneic radiation chimera in the complete absence of any detectable T cell function is not clear at present. However, these preactivated M phi display an important protective effect against L. monocytogenes: chimeras could eliminate Listeria without acquisition of positive delayed-type sensitivity when infected with 10(3) bacteria. An inoculum of 5 . 10(3) L. monocytogenes resulted either in prolonged survival compared with normal mice of the recipient haplotype or in definitive survival accompanied by a positive delayed-type sensitivity

  15. Impaired endothelial progenitor cell mobilization and dysfunctional bone marrow stroma in diabetes mellitus.

    Science.gov (United States)

    Westerweel, Peter E; Teraa, Martin; Rafii, Shahin; Jaspers, Janneke E; White, Ian A; Hooper, Andrea T; Doevendans, Pieter A; Verhaar, Marianne C

    2013-01-01

    Circulating Endothelial Progenitor Cell (EPC) levels are reduced in diabetes mellitus. This may be a consequence of impaired mobilization of EPC from the bone marrow. We hypothesized that under diabetic conditions, mobilization of EPC from the bone marrow to the circulation is impaired -at least partly- due to dysfunction of the bone marrow stromal compartment. Diabetes was induced in mice by streptozotocin injection. Circulating Sca-1(+)Flk-1(+) EPC were characterized and quantified by flow cytometry at baseline and after mobilization with G-CSF/SCF injections. In vivo hemangiogenic recovery was tested by 5-FU challenge. Interaction within the bone marrow environment between CD34(+) hematopoietic progenitor cells (HPC) and supporting stroma was assessed by co-cultures. To study progenitor cell-endothelial cell interaction under normoglycemic and hyperglycemic conditions, a co-culture model using E4Orf1-transfected human endothelial cells was employed. In diabetic mice, bone marrow EPC levels were unaffected. However, circulating EPC levels in blood were lower at baseline and mobilization was attenuated. Diabetic mice failed to recover and repopulate from 5-FU injection. In vitro, primary cultured bone marrow stroma from diabetic mice was impaired in its capacity to support human CFU-forming HPC. Finally, hyperglycemia hampered the HPC supportive function of endothelial cells in vitro. EPC mobilization is impaired under experimental diabetic conditions and our data suggest that diabetes induces alterations in the progenitor cell supportive capacity of the bone marrow stroma, which could be partially responsible for the attenuated EPC mobilization and reduced EPC levels observed in diabetic patients.

  16. Impaired endothelial progenitor cell mobilization and dysfunctional bone marrow stroma in diabetes mellitus.

    Directory of Open Access Journals (Sweden)

    Peter E Westerweel

    Full Text Available Circulating Endothelial Progenitor Cell (EPC levels are reduced in diabetes mellitus. This may be a consequence of impaired mobilization of EPC from the bone marrow. We hypothesized that under diabetic conditions, mobilization of EPC from the bone marrow to the circulation is impaired -at least partly- due to dysfunction of the bone marrow stromal compartment.Diabetes was induced in mice by streptozotocin injection. Circulating Sca-1(+Flk-1(+ EPC were characterized and quantified by flow cytometry at baseline and after mobilization with G-CSF/SCF injections. In vivo hemangiogenic recovery was tested by 5-FU challenge. Interaction within the bone marrow environment between CD34(+ hematopoietic progenitor cells (HPC and supporting stroma was assessed by co-cultures. To study progenitor cell-endothelial cell interaction under normoglycemic and hyperglycemic conditions, a co-culture model using E4Orf1-transfected human endothelial cells was employed.In diabetic mice, bone marrow EPC levels were unaffected. However, circulating EPC levels in blood were lower at baseline and mobilization was attenuated. Diabetic mice failed to recover and repopulate from 5-FU injection. In vitro, primary cultured bone marrow stroma from diabetic mice was impaired in its capacity to support human CFU-forming HPC. Finally, hyperglycemia hampered the HPC supportive function of endothelial cells in vitro.EPC mobilization is impaired under experimental diabetic conditions and our data suggest that diabetes induces alterations in the progenitor cell supportive capacity of the bone marrow stroma, which could be partially responsible for the attenuated EPC mobilization and reduced EPC levels observed in diabetic patients.

  17. Bioactive lipid coating of bone allografts directs engraftment and fate determination of bone marrow-derived cells in rat GFP chimeras.

    Science.gov (United States)

    Das, Anusuya; Segar, Claire E; Chu, Yihsuan; Wang, Tiffany W; Lin, Yong; Yang, Chunxi; Du, Xeujun; Ogle, Roy C; Cui, Quanjun; Botchwey, Edward A

    2015-09-01

    Bone grafting procedures are performed to treat wounds incurred during wartime trauma, accidents, and tumor resections. Endogenous mechanisms of repair are often insufficient to ensure integration between host and donor bone and subsequent restoration of function. We investigated the role that bone marrow-derived cells play in bone regeneration and sought to increase their contributions by functionalizing bone allografts with bioactive lipid coatings. Polymer-coated allografts were used to locally deliver the immunomodulatory small molecule FTY720 in tibial defects created in rat bone marrow chimeras containing genetically-labeled bone marrow for monitoring cell origin and fate. Donor bone marrow contributed significantly to both myeloid and osteogenic cells in remodeling tissue surrounding allografts. FTY720 coatings altered the phenotype of immune cells two weeks post-injury, which was associated with increased vascularization and bone formation surrounding allografts. Consequently, degradable polymer coating strategies that deliver small molecule growth factors such as FTY720 represent a novel therapeutic strategy for harnessing endogenous bone marrow-derived progenitors and enhancing healing in load-bearing bone defects. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Intrathymic T cell differentiation in radiation bone marrow chimeras and its role in T cell emigration to the spleen. An immunohistochemical study

    International Nuclear Information System (INIS)

    Hirokawa, K.; Sado, T.; Kubo, S.; Kamisaku, H.; Hitomi, K.; Utsuyama, M.

    1985-01-01

    Immunohistochemical studies were made on the regeneration of T cells of host- and donor-type in the thymus and spleen of radiation bone marrow chimeras by using B10- and B10.BR-Thy-1 congenic mice. In Thy-1 congenic chimeras, thymocytes of donor bone marrow origin, were first recognized at day 7, when the thymus involuted to the smallest size after the irradiation. The thymocytes of donor-type then proliferated exponentially, showing a slightly faster rate when higher doses of bone marrow cells were used for reconstitution, reaching a level of 100 million by day 17 and completely replacing the cortical thymocytes of host origin by day 21. The replacement of medullary thymocytes from host- to donor-type occurred gradually between days 21 and 35, after the replacement in the cortex was completed. In the spleen, about 1 million survived cells were recovered at day 3 after the irradiation, and approximately 60% of them were shown to be host-type T cells that were observed in the white pulp areas. The host-type T cells in the spleen increased gradually after day 10, due to the influx of host-type T cells from the regenerating thymus. Thus a pronounced increase of T cells of host-type was immunohistochemically observed in the splenic white pulp between days 21 and 28, when thymocytes of host-type were present mainly in the thymic medulla. These host-type T cells were shown to persist in the spleen for a long time, as long as 420 days after the treatment. Phenotypically, they were predominantly Lyt-1+2+ when examined at day 28, but 5 mo later, they were about 50% Lyt-1+2+ and 50% Lyt-1+2-

  19. 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

    International Nuclear Information System (INIS)

    Noguchi, M.; Ogasawara, M.; Iwabuchi, K.; Osgasawara, K.; Ishihara, T.; Good, R.A.; Morikawa, K.; Onoe, K.

    1985-01-01

    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

  20. 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

    International Nuclear Information System (INIS)

    Iwabuchi, K.; Ogasawara, K.; Ogasawara, M.; Yasumizu, R.; Noguchi, M.; Geng, L.; Fujita, M.; Good, R.A.; Onoe, K.

    1987-01-01

    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

  1. Bone marrow endothelial progenitors augment atherosclerotic plaque regression in a mouse model of plasma lipid lowering

    Science.gov (United States)

    Yao, Longbiao; Heuser-Baker, Janet; Herlea-Pana, Oana; Iida, Ryuji; Wang, Qilong; Zou, Ming-Hui; Barlic-Dicen, Jana

    2012-01-01

    The major event initiating atherosclerosis is hypercholesterolemia-induced disruption of vascular endothelium integrity. In settings of endothelial damage, endothelial progenitor cells (EPCs) are mobilized from bone marrow into circulation and home to sites of vascular injury where they aid endothelial regeneration. Given the beneficial effects of EPCs in vascular repair, we hypothesized that these cells play a pivotal role in atherosclerosis regression. We tested our hypothesis in the atherosclerosis-prone mouse model in which hypercholesterolemia, one of the main factors affecting EPC homeostasis, is reversible (Reversa mice). In these mice normalization of plasma lipids decreased atherosclerotic burden; however, plaque regression was incomplete. To explore whether endothelial progenitors contribute to atherosclerosis regression, bone marrow EPCs from a transgenic strain expressing green fluorescent protein under the control of endothelial cell-specific Tie2 promoter (Tie2-GFP+) were isolated. These cells were then adoptively transferred into atheroregressing Reversa recipients where they augmented plaque regression induced by reversal of hypercholesterolemia. Advanced plaque regression correlated with engraftment of Tie2-GFP+ EPCs into endothelium and resulted in an increase in atheroprotective nitric oxide and improved vascular relaxation. Similarly augmented plaque regression was also detected in regressing Reversa mice treated with the stem cell mobilizer AMD3100 which also mobilizes EPCs to peripheral blood. We conclude that correction of hypercholesterolemia in Reversa mice leads to partial plaque regression that can be augmented by AMD3100 treatment or by adoptive transfer of EPCs. This suggests that direct cell therapy or indirect progenitor cell mobilization therapy may be used in combination with statins to treat atherosclerosis. PMID:23081735

  2. Phenotypic and functional properties of murine thymocytes. II. Quantitation of host- and donor-derived cytolytic T lymphocyte precursors in regenerating radiation bone marrow chimeras

    International Nuclear Information System (INIS)

    Ceredig, R.; McDonald, H.R.

    1982-01-01

    Thymocytes from radiation bone marrow chimeras, in which donor bone marrow and irradiated recipient differed at the Thy-1 locus, were stained by indirect immunofluorescence with monoclonal anti-Thy-1 antibodies and analyzed by flow microfluorometry (FMF). Kinetic studies indicated an early appearance of host-derived (CBA, Thy-1.2 + ) thymocytes, which reaches maximum number of 10 to 20 x 10 6 cells at 12 to 16 days after bone marrow reconstitution. Donor-derived (AKR, Thy-1.1 + ) cells were not detectable until 10 to 12 days after reconstitution; subsequently, they increased exponentially in number until 28 days, when they accounted for essentially all cells in the thymus (50 x 10 6 ). Concomitant with the appearance and disappearance of host-derived cells was a change in their Thy-1 surface phenotype. In particular, the proportion of host cells having a ''mature'' phenotype (weakly Thy-1.2 staining) increased progressively with time after irradiation. Functional studies using a sensitive mixed leukocyte microculture system to quantitate cytolytic T lymphocyte precursors (CTL-P) were also carried out in regenerating chimeric thymuses. Initially, the regenerating thymus contained few CTL-P, but by 4 wk after reconstitution, frequencies similar to control adult thymuses were obtained. Analysis of the CTL-P content of host and donor-derived subpopulations, separated either by appropriate anti-Thy-1 antibody plus complement or by direct cell sorting, indicated that both host- and donor-derived cells contained appreciable numbers of CTL-P. Furthermore, increases in CTL-P frequency of both host and donor subpopulations correlated with changes in their surface Thy-1 phenotype

  3. Phenotypic and functional properties of murine thymocytes. II. Quantitation of host- and donor-derived cytolytic T lymphocyte precursors in regenerating radiation bone marrow chimeras

    Energy Technology Data Exchange (ETDEWEB)

    Ceredig, R.; McDonald, H.R.

    1982-02-01

    Thymocytes from radiation bone marrow chimeras, in which donor bone marrow and irradiated recipient differed at the Thy-1 locus, were stained by indirect immunofluorescence with monoclonal anti-Thy-1 antibodies and analyzed by flow microfluorometry (FMF). Kinetic studies indicated an early appearance of host-derived (CBA, Thy-1.2/sup +/) thymocytes, which reaches maximum number of 10 to 20 x 10/sup 6/ cells at 12 to 16 days after bone marrow reconstitution. Donor-derived (AKR, Thy-1.1/sup +/) cells were not detectable until 10 to 12 days after reconstitution; subsequently, they increased exponentially in number until 28 days, when they accounted for essentially all cells in the thymus (50 x 10/sup 6/). Concomitant with the appearance and disappearance of host-derived cells was a change in their Thy-1 surface phenotype. In particular, the proportion of host cells having a ''mature'' phenotype (weakly Thy-1.2 staining) increased progressively with time after irradiation. Functional studies using a sensitive mixed leukocyte microculture system to quantitate cytolytic T lymphocyte precursors (CTL-P) were also carried out in regenerating chimeric thymuses. Initially, the regenerating thymus contained few CTL-P, but by 4 wk after reconstitution, frequencies similar to control adult thymuses were obtained. Analysis of the CTL-P content of host and donor-derived subpopulations, separated either by appropriate anti-Thy-1 antibody plus complement or by direct cell sorting, indicated that both host- and donor-derived cells contained appreciable numbers of CTL-P. Furthermore, increases in CTL-P frequency of both host and donor subpopulations correlated with changes in their surface Thy-1 phenotype.

  4. Immune tolerance in radiation chimeras

    International Nuclear Information System (INIS)

    Awaya, Kazuhiko; Kuniki, Hiromichi; Neki, Miyuki

    1978-01-01

    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., F 1 -type cells. F 1 -type lymphocytes can distinguish parental strain cells from themselves. In these chimeras, a F 1 -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 F 1 -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.)

  5. Biocompatibility of Poly-ε-caprolactone-hydroxyapatite composite on mouse bone marrow-derived osteoblasts and endothelial cells

    Directory of Open Access Journals (Sweden)

    Wooley Paul H

    2009-02-01

    Full Text Available Abstract Background Tissue-engineered bone may be developed by seeding the cells capable of both osteogenesis and vascularization on biocompatible composite scaffolds. The current study investigated the performance of mice bone marrow-derived osteogenic cells and endothelial cells as seeded on hydroxyapatite (HA and poly-ε-caprolactone (PCL composite scaffolds. Methods Mononuclear cells were induced to osteoblasts and endothelial cells respectively, which were defined by the expression of osteocalcin, alkaline phosphatase (ALP, and deposits of calcium-containing crystal for osteoblasts, or by the expression of vascular endothelial growth factor receptor-2 (VEGFR-2 and von Willebrand factor (vWF, and the formation of a capillary network in Matrigel™ for endothelial cells. Both types of cell were seeded respectively on PCL-HA scaffolds at HA to PCL weight ratio of 1:1, 1:4, or 0:1 and were evaluated using scanning electron microscopy, ALP activity (of osteoblasts and nitric oxide production (of endothelial cells plus the assessment of cell viability. Results The results indicated that HA led to a positive stimulation of osteoblasts viability and ALP activity, while HA showed less influence on endothelial cells viability. An elevated nitric oxide production of endothelial cells was observed in HA-containing group. Conclusion Supplement of HA into PCL improved biocompatible for bone marrow-derived osteoblasts and endothelial cells. The PCL-HA composite integrating with two types of cells may provide a useful system for tissue-engineered bone grafts with vascularization.

  6. 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

    International Nuclear Information System (INIS)

    Speiser, D.E.; Chvatchko, Y.; Zinkernagel, R.M.; MacDonald, H.R.

    1990-01-01

    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

  7. Endothelial Nitric Oxide Synthase Overexpression Restores the Efficiency of Bone Marrow Mononuclear Cell-Based Therapy

    Science.gov (United States)

    Mees, Barend; Récalde, Alice; Loinard, Céline; Tempel, Dennie; Godinho, Marcia; Vilar, José; van Haperen, Rien; Lévy, Bernard; de Crom, Rini; Silvestre, Jean-Sébastien

    2011-01-01

    Bone marrow-derived mononuclear cells (BMMNCs) enhance postischemic neovascularization, and their therapeutic use is currently under clinical investigation. However, cardiovascular risk factors, including diabetes mellitus and hypercholesterolemia, lead to the abrogation of BMMNCs proangiogenic potential. NO has been shown to be critical for the proangiogenic function of BMMNCs, and increased endothelial NO synthase (eNOS) activity promotes vessel growth in ischemic conditions. We therefore hypothesized that eNOS overexpression could restore both the impaired neovascularization response and decreased proangiogenic function of BMMNCs in clinically relevant models of diabetes and hypercholesterolemia. Transgenic eNOS overexpression in diabetic, atherosclerotic, and wild-type mice induced a 1.5- to 2.3-fold increase in postischemic neovascularization compared with control. eNOS overexpression in diabetic or atherosclerotic BMMNCs restored their reduced proangiogenic potential in ischemic hind limb. This effect was associated with an increase in BMMNC ability to differentiate into cells with endothelial phenotype in vitro and in vivo and an increase in BMMNCs paracrine function, including vascular endothelial growth factor A release and NO-dependent vasodilation. Moreover, although wild-type BMMNCs treatment resulted in significant progression of atherosclerotic plaque in ischemic mice, eNOS transgenic atherosclerotic BMMNCs treatment even had antiatherogenic effects. Cell-based eNOS gene therapy has both proangiogenic and antiatherogenic effects and should be further investigated for the development of efficient therapeutic neovascularization designed to treat ischemic cardiovascular disease. PMID:21224043

  8. T cells from fully H-2 allogeneic (A replaced by B) radiation bone marrow chimeras are functionally competent and host restricted but are alloreactive against hybrid Ia determinants expressed on (A x B)F1 cells

    International Nuclear Information System (INIS)

    Kruisbeek, A.M.; Hathcock, K.S.; Hodes, R.J.; Singer, A.

    1982-01-01

    In this communication it is demonstrated that T cells from fully allogeneic A replaced by B radiation bone marrow chimeras are alloreactive against the hybrid Ia molecules expressed on the surface of heterozygous A X B cells. These results suggested that previous failures to generate cytotoxic T lymphocyte (CTL) responses from fully allogeneic chimeras by sensitizing the chimeric T cells to antigen in an (A X B)F1-priming environment might have been confounded by an ongoing alloreaction against determinants created by hybrid Ia molecules expressed on F1 cells. Consequently, the ability to generate CTL responses from fully allogeneic chimeras was re-examined by sensitizing the chimeric T cells to antigen presented by homozygous rather that F1 stimulator cells. It was found that T cells of donor bone marrow origin that mediate cytotoxic responses to trinitrophenyl-modified self determinants do differentiate into functional competence in an H-2-incompatible host environment and are restricted to the host H-2 haplotype

  9. An integrin alpha4beta7•IgG heterodimeric chimera binds to MAdCAM-1 on high endothelial venules in gut-associated lymphoid tissue.

    Science.gov (United States)

    Hoshino, Hitomi; Kobayashi, Motohiro; Mitoma, Junya; Sato, Yoshiko; Fukuda, Minoru; Nakayama, Jun

    2011-06-01

    Lymphocyte homing is regulated by a multistep process mediated by sequential adhesive interactions between circulating lymphocytes and high endothelial venules (HEVs). In gut-associated lymphoid tissue (GALT), the initial interactive step, "tethering and rolling," is partly mediated by integrin α4β7 expressed on GALT-homing lymphocytes and its ligand MAdCAM-1, which is exclusively expressed on HEVs in GALT. To probe functional MAdCAM-1 in tissue sections, we developed a soluble integrin α4β7 heterodimeric IgG chimera by joining the extracellular region of mouse integrin α4 and β7 subunits to a human IgG Fc domain. Western blot analysis revealed that co-transfection of HEK 293T cells with expression vectors encoding integrin α4•IgG and β7•IgG results in the formation of α4β7•IgG heterodimeric chimeras. This complex preferentially binds to CHO cells expressing MAdCAM-1 and, to a lesser extent, to cells expressing VCAM-1, but not to cells expressing ICAM-1. Moreover, α4β7•IgG specifically binds to HEVs in GALT in situ in a divalent cation-dependent fashion and inhibits lymphocyte binding to HEVs in GALT. These findings indicate that α4β7•IgG can be used as a probe for functional MAdCAM-1 expressed on HEVs in GALT and could potentially serve as an anti-inflammatory drug inhibiting GALT-specific lymphocyte migration.

  10. Bone marrow vascular endothelial growth factor level per platelet count might be a significant predictor for the treatment outcomes of patients with diffuse large B-cell lymphomas.

    Science.gov (United States)

    Kim, Jung Sun; Gang, Ga Won; Lee, Se Ryun; Sung, Hwa Jung; Park, Young; Kim, Dae Sik; Choi, Chul Won; Kim, Byung Soo

    2015-10-01

    Developing a parameter to predict bone marrow invasion by non-Hodgkin's lymphoma is an important unmet medical need for treatment decisions. This study aimed to confirm the validity of the hypothesis that bone marrow plasma vascular endothelial growth factor level might be correlated with the risk of bone marrow involvement and the prognosis of patients with diffuse large B-cell non-Hodgkin's lymphoma. Forty-nine diffuse large B-cell lymphoma patients treated with rituximab, cyclophosphamide, daunorubicin, vincristine and prednisolone regimen were enrolled. Vascular endothelial growth factor level was measured with enzyme-linked immunosorbent assay. The validity of bone marrow plasma vascular endothelial growth factor level and bone marrow vascular endothelial growth factor level per platelet count for predicting treatment response and survival after initial rituximab, cyclophosphamide, daunorubicin, vincristine and prednisolone combined chemotherapy was assessed. Bone marrow plasma vascular endothelial growth factor level per platelet count was significantly associated with old age (≥ 65 years), poor performance score (≥ 2), high International prognosis index (≥ 3) and bone marrow invasion. The patients with high bone marrow plasma vascular endothelial growth factor level per platelet count (≥ 3.01) showed a significantly lower complete response rate than the others. On Kaplan-Meier survival curves, the patients with high bone marrow plasma vascular endothelial growth factor levels (≥ 655 pg/ml) or high bone marrow plasma vascular endothelial growth factor level per platelet count (≥ 3.01) demonstrated a significantly shorter overall survival and progression-free survival than the others. In the patients without bone marrow involvement, bone marrow plasma vascular endothelial growth factor level per platelet count had a significant relationship with overall survival and progression-free survival. Multivariate analysis revealed that the patients without

  11. Characterization of xenogeneic mouse-to-rat bone marrow chimeras. I. Examination of hematologic and immunologic function

    International Nuclear Information System (INIS)

    Wade, A.C.; Luckert, P.H.; Tazume, S.; Niedbalski, J.L.; Pollard, M.

    1987-01-01

    Eighteen xenogeneic chimeric rats (survival: greater than 100 days) were established by transplanting bone marrow cells from femurs of 10 gnotobiotic CFW mice into each germfree Sprague-Dawley or Wistar rat. The erythrocytes circulating in the rats were of mouse origin as determined by hemagglutination. Hemoglobin electrophoresis, radial immunodiffusion for IgG, and assay of granulocytic neutrophils for leukocyte alkaline phosphatase verified that true chimerism was achieved. The extent of hematological and immunological reconstitution varied. In general, hematocrit levels were low to normal, white blood cell counts and differentials were within normal limits, and serum protein levels were normal. Levels of circulating IgG of each species were comparable to those of germfree rat and mouse controls. Natural killer (NK) activity was depressed, a phenomenon that may be attributable to the radiation treatment of recipients, or to failure to transfer NK cells or precursors. Mitogenic stimulation reactions were varied, but most chimeric rats demonstrated moderately depressed responses. Reactions as a whole suggested that gnotobiotic rats with xenogeneic bone marrow are incompletely reconstituted, both hematologically and immunologically. No acute graft-versus-host reaction was seen

  12. Bat-mouse bone marrow chimera: a novel animal model for dissecting the uniqueness of the bat immune system.

    Science.gov (United States)

    Yong, Kylie Su Mei; Ng, Justin Han Jia; Her, Zhisheng; Hey, Ying Ying; Tan, Sue Yee; Tan, Wilson Wei Sheng; Irac, Sergio Erdal; Liu, Min; Chan, Xue Ying; Gunawan, Merry; Foo, Randy Jee Hiang; Low, Dolyce Hong Wen; Mendenhall, Ian Hewitt; Chionh, Yok Teng; Dutertre, Charles-Antoine; Chen, Qingfeng; Wang, Lin-Fa

    2018-03-16

    Bats are an important animal model with long lifespans, low incidences of tumorigenesis and an ability to asymptomatically harbour pathogens. Currently, in vivo studies of bats are hampered due to their low reproduction rates. To overcome this, we transplanted bat cells from bone marrow (BM) and spleen into an immunodeficient mouse strain NOD-scid IL-2R -/- (NSG), and have successfully established stable, long-term reconstitution of bat immune cells in mice (bat-mice). Immune functionality of our bat-mouse model was demonstrated through generation of antigen-specific antibody response by bat cells following immunization. Post-engraftment of total bat BM cells and splenocytes, bat immune cells survived, expanded and repopulated the mouse without any observable clinical abnormalities. Utilizing bat's remarkable immunological functions, this novel model has a potential to be transformed into a powerful platform for basic and translational research.

  13. Corneal endothelial expansion promoted by human bone marrow mesenchymal stem cell-derived conditioned medium.

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    Makiko Nakahara

    Full Text Available Healthy corneal endothelium is essential for maintaining corneal clarity, as the damage of corneal endothelial cells and loss of cell count causes severe visual impairment. Corneal transplantation is currently the only therapy for severe corneal disorders. The greatly limited proliferative ability of human corneal endothelial cells (HCECs, even in vitro, has challenged researchers to establish efficient techniques for the cultivating HCECs, a pivotal issue for clinical applications. The aim of this study was to evaluate conditioned medium (CM obtained from human bone marrow-derived mesenchymal stem cells (MSCs (MSC-CM for use as a consistent expansion protocol of HCECs. When HCECs were maintained in the presence of MSC-CM, cell morphology assumed a hexagonal shape similar to corneal endothelial cells in vivo, as opposed to the irregular cell shape observed in control cultures in the absence of MSC-CM. They also maintained the functional protein phenotypes; ZO-1 and Na(+/K(+-ATPase were localized at the intercellular adherent junctions and pump proteins of corneal endothelium were accordingly expressed. In comparison to the proliferative potential observed in the control cultures, HCECs maintained in MSC-CM were found to have more than twice as many Ki67-positive cells and a greatly increased incorporation of BrdU into DNA. MSC-CM further facilitated the cell migration of HCECs. Lastly, the mechanism of cell proliferation mediated by MSC-CM was investigated, and phosphorylation of Akt and ERK1/2 was observed in HCECs after exposure to MSC-CM. The inhibitor to PI 3-kinase maintained the level of p27(Kip1 for up to 24 hours and greatly blocked the expression of cyclin D1 and D3 during the early G1 phase, leading to the reduction of cell density. These findings indicate that MSC-CM not only stimulates the proliferation of HCECs by regulating the G1 proteins of the cell cycle but also maintains the characteristic differentiated phenotypes necessary

  14. Effects of T cell depletion in radiation bone marrow chimeras. I. Evidence for a donor cell population which increases allogeneic chimerism but which lacks the potential to produce GVHD

    International Nuclear Information System (INIS)

    Sykes, M.; Sheard, M.; Sachs, D.H.

    1988-01-01

    The opposing problems of graft-vs-host disease (GVHD) and failure of alloengraftment present major obstacles to the application of bone marrow transplantation (BMT) across complete MHC barriers. The addition of syngeneic T-cell-depleted (TCD) bone marrow (BM) to untreated fully allogeneic marrow inocula in lethally irradiated mice has been previously shown to provide protection from GVHD. We have used this model to study the effects of allogeneic T cells on levels of chimerism in recipients of mixed marrow inocula. The results indicate that T cells in allogeneic BM inocula eliminate both coadministered recipient-strain and radioresistant host hematopoietic elements to produce complete allogeneic chimerism without clinical GVHD. To determine the role of GVH reactivity in this phenomenon, we performed similar studies in an F1 into parent combination, in which the genetic potential for GVHD is lacking. The presence of T cells in F1 marrow inocula led to predominant repopulation with F1 lymphocytes in such chimeras, even when coadministered with TCD-recipient-strain BM. These results imply that the ability of allogeneic BM cells removed by T cell depletion to increase levels of allochimerism may be mediated by a population which is distinct from that which produces GVHD. These results may have implications for clinical BM transplantation

  15. A PEDF-Derived Peptide Inhibits Retinal Neovascularization and Blocks Mobilization of Bone Marrow-Derived Endothelial Progenitor Cells

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    Richard Longeras

    2012-01-01

    Full Text Available Proliferative diabetic retinopathy is characterized by pathological retinal neovascularization, mediated by both angiogenesis (involving mature endothelial cells and vasculogenesis (involving bone marrow-derived circulating endothelial progenitor cells (EPCs. Pigment epithelium-derived factor (PEDF contains an N-terminal 34-amino acid peptide (PEDF-34 that has antiangiogenic properties. Herein, we present a novel finding that PEDF-34 also possesses antivasculogenic activity. In the oxygen-induced retinopathy (OIR model using transgenic mice that have Tie2 promoter-driven GFP expression, we quantified Tie2GFP+ cells in bone marrow and peripheral blood by fluorescence-activated cell sorting (FACS. OIR significantly increased the number of circulating Tie2-GFP+ at P16, correlating with the peak progression of neovascularization. Daily intraperitoneal injections of PEDF-34 into OIR mice decreased the number of Tie2-GFP+ cells in the circulation at P16 by 65% but did not affect the number of Tie2-GFP+ cells in the bone marrow. These studies suggest that PEDF-34 attenuates EPC mobilization from the bone marrow into the blood circulation during retinal neovascularization.

  16. Effect of selective T cell depletion of host and/or donor bone marrow on lymphopoietic repopulation, tolerance, and graft-vs-host disease in mixed allogeneic chimeras (B10 + B10.D2----B10)

    International Nuclear Information System (INIS)

    Ildstad, S.T.; Wren, S.M.; Bluestone, J.A.; Barbieri, S.A.; Stephany, D.; Sachs, D.H.

    1986-01-01

    Reconstitution of lethally irradiated mice with a mixture of T cell-depleted syngeneic plus T cell-depleted allogeneic bone marrow (B10 + B10.D2----B10) leads to the induction of mixed lymphopoietic chimerism, excellent survivals, specific in vivo transplantation tolerance to subsequent donor strain skin grafts, and specific in vitro unresponsiveness to allogeneic donor lymphoid elements as assessed by mixed lymphocyte reaction (MLR) proliferative and cell-mediated lympholysis (CML) cytotoxicity assays. When B10 recipient mice received mixed marrow inocula in which the syngeneic component had not been T cell depleted, whether or not the allogeneic donor marrow was treated, they repopulated exclusively with host-type cells, promptly rejected donor-type skin allografts, and were reactive in vitro to the allogeneic donor by CML and MLR assays. In contrast, T cell depletion of the syngeneic component of the mixed marrow inocula resulted in specific acceptance of allogeneic donor strain skin grafts. Such animals were specifically unreactive to allogeneic donor lymphoid elements in vitro by CML and MLR, but were reactive to third party. When both the syngeneic and allogeneic marrow were T cell depleted, variable percentages of host- and donor-type lymphoid elements were detected in the mixed reconstituted host. When only the syngeneic bone marrow was T cell depleted, animals repopulated exclusively with donor-type cells. Although these animals had detectable in vitro anti-host (B10) reactivity by CML and MLR and reconstituted as fully allogeneic chimeras, they exhibited excellent survival and had no in vivo evidence for graft-vs-host disease. Experiments in which untreated donor spleen cells were added to the inocula in this last group suggest that the presence of T cell-depleted syngeneic bone marrow cells diminishes graft-vs-host disease and the mortality from it

  17. Cilostazol activates function of bone marrow-derived endothelial progenitor cell for re-endothelialization in a carotid balloon injury model.

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    Rie Kawabe-Yako

    Full Text Available BACKGROUND: Cilostazol(CLZ has been used as a vasodilating anti-platelet drug clinically and demonstrated to inhibit proliferation of smooth muscle cells and effect on endothelial cells. However, the effect of CLZ on re-endothelialization including bone marrow (BM-derived endothelial progenitor cell (EPC contribution is unclear. We have investigated the hypothesis that CLZ might accelerate re-endothelialization with EPCs. METHODOLOGY/PRINCIPAL FINDINGS: Balloon carotid denudation was performed in male Sprague-Dawley rats. CLZ group was given CLZ mixed feed from 2 weeks before carotid injury. Control group was fed normal diet. CLZ accelerated re-endothelialization at 2 weeks after surgery and resulted in a significant reduction of neointima formation 4 weeks after surgery compared with that in control group. CLZ also increased the number of circulating EPCs throughout the time course. We examined the contribution of BM-derived EPCs to re-endothelialization by BM transplantation from Tie2/lacZ mice to nude rats. The number of Tie2-regulated X-gal positive cells on injured arterial luminal surface was increased at 2 weeks after surgery in CLZ group compared with that in control group. In vitro, CLZ enhanced proliferation, adhesion and migration activity, and differentiation with mRNA upregulation of adhesion molecule integrin αvβ3, chemokine receptor CXCR4 and growth factor VEGF assessed by real-time RT-PCR in rat BM-derived cultured EPCs. In addition, CLZ markedly increased the expression of SDF-1α that is a ligand of CXCR4 receptor in EPCs, in the media following vascular injury. CONCLUSIONS/SIGNIFICANCE: CLZ promotes EPC mobilization from BM and EPC recruitment to sites of arterial injury, and thereby inhibited neointima formation with acceleration of re-endothelialization with EPCs as well as pre-existing endothelial cells in a rat carotid balloon injury model. CLZ could be not only an anti-platelet agent but also a promising tool for

  18. Hematopoietic microenvironment. Origin, lineage, and transplantability of the stromal cells in long-term bone marrow cultures from chimeric mice

    International Nuclear Information System (INIS)

    Perkins, S.; Fleischman, R.A.

    1988-01-01

    Studies of bone marrow transplant patients have suggested that the stromal cells of the in vitro hematopoietic microenvironment are transplantable into conditioned recipients. Moreover, in patients with myeloproliferative disorders, all of the stromal cells, which include presumptive endothelial cells, appear to be derived from hematopoietic precursors. To confirm these findings, we have constructed two chimeric mouse models: (a) traditional radiation chimeras, and (b) fetal chimeras, produced by placental injection of bone marrow into genetically anemic Wx/Wv fetuses, a technique that essentially precludes engraftment of nonhematopoietic cells. Using two-color indirect immunofluorescence, the stromal cells in long-term bone marrow culture derived from these chimeras were analyzed for donor or host origin by strain-specific H-2 antigens, and for cell lineage by a variety of other specific markers. 75-95% of the stromal cells were shown to be hematopoietic cells of the monocyte-macrophage lineage, based upon donor origin, phagocytosis, and expression of specific hematopoietic surface antigens. The remaining 5-25% of the stromal cells were exclusively host in origin. Apart from occasional fat cells, these cells uniformly expressed collagen type IV, laminin, and a surface antigen associated with endothelial cells. Since these endothelial-like cells are not transplantable into radiation or fetal chimeras, they are not derived from hematopoietic stem cells. The contrast between our findings and human studies suggests either unexpected species differences in the origin of stromal lineages or limitations in the previous methodology used to detect nonhematopoietic stromal cells

  19. Allogeneic radiation chimeras induced in SPF mice

    International Nuclear Information System (INIS)

    Sado, Toshihiko; Kamisaku, Hitoko

    1977-01-01

    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.)

  20. Paracrine effects of bone marrow-derived endothelial progenitor cells: cyclooxygenase-2/prostacyclin pathway in pulmonary arterial hypertension.

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    Dong-Mei Jiang

    Full Text Available BACKGROUND: Endothelial dysfunction is the pathophysiological characteristic of pulmonary arterial hypertension (PAH. Some paracrine factors secreted by bone marrow-derived endothelial progenitor cells (BMEPCs have the potential to strengthen endothelial integrity and function. This study investigated whether BMEPCs have the therapeutic potential to improve monocrotaline (MCT-induced PAH via producing vasoprotective substances in a paracrine fashion. METHODS AND RESULTS: Bone marrow-derived mononuclear cells were cultured for 7 days to yield BMEPCs. 24 hours or 3 weeks after exposure to BMEPCs in vitro or in vivo, the vascular reactivity, cyclooxygenase-2 (COX-2 expression, prostacyclin (PGI2 and cAMP release in isolated pulmonary arteries were examined respectively. Treatment with BMEPCs could improve the relaxation of pulmonary arteries in MCT-induced PAH and BMEPCs were grafted into the pulmonary bed. The COX-2/prostacyclin synthase (PGIS and its progenies PGI2/cAMP were found to be significantly increased in BMEPCs treated pulmonary arteries, and this action was reversed by a selective COX-2 inhibitor, NS398. Moreover, the same effect was also observed in conditioned medium obtained from BMEPCs culture. CONCLUSIONS: Implantation of BMEPCs effectively ameliorates MCT-induced PAH. Factors secreted in a paracrine fashion from BMEPCs promote vasoprotection by increasing the release of PGI2 and level of cAMP.

  1. Treatment with platelet lysate induces endothelial differentation of bone marrow mesenchymal stem cells under fluid shear stress.

    Science.gov (United States)

    Homayouni Moghadam, Farshad; Tayebi, Tahereh; Moradi, Alireza; Nadri, Hamid; Barzegar, Kazem; Eslami, Gilda

    2014-01-01

    By considering stem cell-based therapies as a new hope for the treatment of some tragic diseases, marrow stromal cells or marrow mesenchymal stem cells (MSCs) were considered as a suitable and safe multipotential cell source for this new therapeutic approach. For this purpose, many investigations have been performed on differentiation of MSCs toward specific cell lines to overcome the demand for providing the organ specific cells for cell therapy or preparation of engineered tissues. In the present study, differentiation of MSCs to endothelial cells (ECs) by mechanical and chemical stimulation was evaluated. Fluid shear stress (FSS) was used as mechanical inducer, while platelet lysate (PL) and estradiol (E) were used as chemical induction factors. MSCs were placed under FSS with different forces (2, 5 and 10dyn/cm(2)) for different periods (6, 12 and 24 hours). In some groups, PL and E were added to the culture media to evaluate their effect on expression of EC specific markers. This investigation revealed that FSS with low tension (2.5-5 dyn/cm(2)) for a long time (24 hours) or high tension (10 dyn/cm(2)) in short time (6 hours) in the presence of PL could differentiate MSCs toward ECs. The presence of PL was necessary for initiation of endothelial differentiation, and in the absence of PL, there was not any expression of CD34 and Cadherin5 (Cdh5) among cells. Adding E to the culture medium did not change the rate of endothelial differentiation under FSS. Generated endothelial progenitors could produce von Willebrand factor (vWF) after two weeks culture and also they formed tubular structures after culture on matrigel.

  2. H-2 restriction specificity of T cells from H-2 incompatible radiation bone marrow chimeras: further evidence for the absence of crucial influence of the host/thymus environment on the generation of H-2 restricted TNP-specific T lymphocyte precursors

    International Nuclear Information System (INIS)

    Aizawa, S.; Sado, T.; Kubo, E.

    1984-01-01

    Experiments were conducted to answer the questions related to (a) the role played by the antigen-presenting cells (APCs) present within the thymus and (b) the effect of radiation dose to the recipients on the H-2 restriction profile of TNP-specific cytotoxic T lymphocyte precursors (CTLP) recovered from spleens and/or thymuses of H-2 incompatible radiation bone marrow chimeras (BMC). The H-2 restriction profile of intrathymically differentiating TNP-specific CTLPs was also analyzed in order to test an argument that donor-H-2 restricted CTLP detected in spleens of H-2 incompatible BMC were due to the extrathymically differentiated T cells under the influence of donor-derived lymphoreticular cells. The results indicated the following: (i) splenic T cells from B10(H-2b) leads to (B10(H-2b) leads to B10.BR(H-2k)) chimeras, which were constructed by irradiating primary B10 leads to B10.BR chimeras with 1100 R and reconstituting them with donor-type (B10) bone marrow cells as long as 8 months after their construction, manifested restriction specificities for both donor- and host-type H-2, (ii) splenic T cells from two types of (B10 X B10.BR)F1 leads to B10 chimeras which were reconstituted after exposure of the recipients with either 900 or 1100 R with donor-type bone marrow cells generated both donor- and host-H-2 restricted TNP-specific cytotoxic T cells, and (iii) the TNP-specific CTLPs present in the regenerating thymuses of B10.BR leads to B10 and (B10 X B10.BR)F1 leads to B10 chimeras 4 weeks after their construction were also shown to manifest both donor- and host-H-2 restriction specificities. The significance of these findings on the H-2 restriction profile of CTLP generated in BMCs is discussed

  3. Physiology of B cells in mice with X-linked immunodeficiency (xid). III. Disappearance of xid B cells in double bone marrow chimeras

    International Nuclear Information System (INIS)

    Sprent, J.; Bruce, J.

    1984-01-01

    Evidence is presented that B cells from mice with X-linked immunodeficiency (xid) differentiate at a slower rate than normal B cells. This conclusion stems from studies in which (B6 X CBA/J)F1 mice were heavily irradiated (1,000 rads) and reconstituted with a mixture of T-depleted marrow cells taken from (a) nondefective B6 mice (H-2b) and (b) xid CBA/N or nondefective CBA/Ca mice (both H-2k). With transfer of CBA/Ca plus B6 marrow cells, the irradiated recipients become repopulated with B cells derived from both parental marrow sources; except for an early imbalance (probably reflecting Hh resistance), the degree of chimerism remained relatively stable over a period of more than 6 months. Very different results occurred with transfer of a mixture of xid CBA/N and normal B6 marrow. Within the first 2 months after marrow reconstitution, a low but significant proportion of the B cells in both spleen and lymph nodes were of CBA/N origin. Thereafter the proportion of these cells fell progressively, and by 6-9 months virtually all of the B cells were of B6 origin. This gradual decline in CBA/N-derived cells did not apply to other cell types, i.e., T cells or pluripotential stem cells. Analogous results were obtained with transfer of CBA/N vs. CBA/Ca marrow cells into sublethally irradiated (750 rads) (CBA/N X DBA/2)F1 male vs. female mice. For example, CBA/N-marrow derived B cells differentiated effectively and survived for long periods in F1 male mice (xid----xid) but not in F1 female mice (xid----normal). The finding that xid B cells eventually disappear in the presence of normal B cells strengthens the view that xid B cells are an abnormal population not represented in normal mice

  4. Mobilization of endogenous bone marrow derived endothelial progenitor cells and therapeutic potential of parathyroid hormone after ischemic stroke in mice.

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    Li-Li Wang

    Full Text Available Stroke is a major neurovascular disorder threatening human life and health. Very limited clinical treatments are currently available for stroke patients. Stem cell transplantation has shown promising potential as a regenerative treatment after ischemic stroke. The present investigation explores a new concept of mobilizing endogenous stem cells/progenitor cells from the bone marrow using a parathyroid hormone (PTH therapy after ischemic stroke in adult mice. PTH 1-34 (80 µg/kg, i.p. was administered 1 hour after focal ischemia and then daily for 6 consecutive days. After 6 days of PTH treatment, there was a significant increase in bone marrow derived CD-34/Fetal liver kinase-1 (Flk-1 positive endothelial progenitor cells (EPCs in the peripheral blood. PTH treatment significantly increased the expression of trophic/regenerative factors including VEGF, SDF-1, BDNF and Tie-1 in the brain peri-infarct region. Angiogenesis, assessed by co-labeled Glut-1 and BrdU vessels, was significantly increased in PTH-treated ischemic brain compared to vehicle controls. PTH treatment also promoted neuroblast migration from the subventricular zone (SVZ and increased the number of newly formed neurons in the peri-infarct cortex. PTH-treated mice showed significantly better sensorimotor functional recovery compared to stroke controls. Our data suggests that PTH therapy improves endogenous repair mechanisms after ischemic stroke with functional benefits. Mobilizing endogenous bone marrow-derived stem cells/progenitor cells using PTH and other mobilizers appears an effective and feasible regenerative treatment after ischemic stroke.

  5. Endothelial Progenitor Cell Fraction Contained in Bone Marrow-Derived Mesenchymal Stem Cell Populations Impairs Osteogenic Differentiation

    Directory of Open Access Journals (Sweden)

    Fabian Duttenhoefer

    2015-01-01

    Full Text Available In bone tissue engineering (TE endothelial cell-osteoblast cocultures are known to induce synergies of cell differentiation and activity. Bone marrow mononucleated cells (BMCs are a rich source of mesenchymal stem cells (MSCs able to develop an osteogenic phenotype. Endothelial progenitor cells (EPCs are also present within BMC. In this study we investigate the effect of EPCs present in the BMC population on MSCs osteogenic differentiation. Human BMCs were isolated and separated into two populations. The MSC population was selected through plastic adhesion capacity. EPCs (CD34+ and CD133+ were removed from the BMC population and the resulting population was named depleted MSCs. Both populations were cultured over 28 days in osteogenic medium (Dex+ or medium containing platelet lysate (PL. MSC population grew faster than depleted MSCs in both media, and PL containing medium accelerated the proliferation for both populations. Cell differentiation was much higher in Dex+ medium in both cases. Real-time RT-PCR revealed upregulation of osteogenic marker genes in depleted MSCs. Higher values of ALP activity and matrix mineralization analyses confirmed these results. Our study advocates that absence of EPCs in the MSC population enables higher osteogenic gene expression and matrix mineralization and therefore may lead to advanced bone neoformation necessary for TE constructs.

  6. Antibody responses in allogeneic radiation chimeras

    International Nuclear Information System (INIS)

    Coico, R.F.

    1982-01-01

    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

  7. Bioactive lipid coating of bone allografts directs engraftment and fate determination of bone marrow-derived cells in rat GFP chimeras

    OpenAIRE

    Das, Anusuya; Segar, Claire E.; Chu, Yihsuan; Wang, Tiffany W.; Lin, Yong; Yang, Chunxi; Du, Xeujun; Ogle, Roy C.; Cui, Quanjun; Botchwey, Edward A.

    2015-01-01

    Bone grafting procedures are performed to treat wounds incurred during wartime trauma, accidents, and tumor resections. Endogenous mechanisms of repair are often insufficient to ensure integration between host and donor bone and subsequent restoration of function. We investigated the role that bone marrow-derived cells play in bone regeneration and sought to increase their contributions by functionalizing bone allografts with bioactive lipid coatings. Polymer-coated allografts were used to lo...

  8. bg/sup J//bg/sup J/:W/W/sup v/ bone marrow chimera. A model for studying stem cell regulation

    Energy Technology Data Exchange (ETDEWEB)

    Patt, H M; Maloney, M A

    1978-01-01

    In studies with bg/sup J//bg/sup J/:W/W/sup v/ chimeric mice, we used the beige neutrophil marker as a criterion of W/W/sup v/ marrow replacement by implanted bg/sup J//bg/sup J/ stem cells. Data from a 50-fold range of inoculum doses and a 2 y period of observation indicate a hyperbolic pattern of replacement expressed as a log dose-response relationship. The saturating effect with increasing inoculum dose was interpreted as reflecting random initial stem cell seeding in bone marrow coupled with a decreasing efficiency of colonization by migration. From the statistics of random sampling and the exponential decrease of the 63% replacement dose with time, we estimate that W/W/sup v/ marrow contains about 2600 stem cell regulatory volumes of about 10/sup 8/ ..mu../sup 3/ (50 cell diameters) each, a dimension consistent with concepts of short-range cell-cell interactions. Our observations suggest that each regulatory volume is essentially self-contained and that stem cell migration is generally restricted to contiguous volumes.

  9. Quantum chimera states

    Energy Technology Data Exchange (ETDEWEB)

    Viennot, David, E-mail: david.viennot@utinam.cnrs.fr; Aubourg, Lucile

    2016-02-15

    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. - Highlights: • We propose a spin chain model with long range couplings having purely quantum states similar to the classical chimera states. • The quantum chimera states are characterized by the coexistence of strongly entangled and non-entangled spins in the same chain. • The quantum chimera states present some characteristics of quantum chaos.

  10. Quantum chimera states

    International Nuclear Information System (INIS)

    Viennot, David; Aubourg, Lucile

    2016-01-01

    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 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. - Highlights: • We propose a spin chain model with long range couplings having purely quantum states similar to the classical chimera states. • The quantum chimera states are characterized by the coexistence of strongly entangled and non-entangled spins in the same chain. • The quantum chimera states present some characteristics of quantum chaos.

  11. Endothelial Cells Promote Expansion of Long-Term Engrafting Marrow Hematopoietic Stem and Progenitor Cells in Primates.

    Science.gov (United States)

    Gori, Jennifer L; Butler, Jason M; Kunar, Balvir; Poulos, Michael G; Ginsberg, Michael; Nolan, Daniel J; Norgaard, Zachary K; Adair, Jennifer E; Rafii, Shahin; Kiem, Hans-Peter

    2017-03-01

    Successful expansion of bone marrow (BM) hematopoietic stem and progenitor cells (HSPCs) would benefit many HSPC transplantation and gene therapy/editing applications. However, current expansion technologies have been limited by a loss of multipotency and self-renewal properties ex vivo. We hypothesized that an ex vivo vascular niche would provide prohematopoietic signals to expand HSPCs while maintaining multipotency and self-renewal. To test this hypothesis, BM autologous CD34 + cells were expanded in endothelial cell (EC) coculture and transplanted in nonhuman primates. CD34 + C38 - HSPCs cocultured with ECs expanded up to 17-fold, with a significant increase in hematopoietic colony-forming activity compared with cells cultured with cytokines alone (colony-forming unit-granulocyte-erythroid-macrophage-monocyte; p < .005). BM CD34 + cells that were transduced with green fluorescent protein lentivirus vector and expanded on ECs engrafted long term with multilineage polyclonal reconstitution. Gene marking was observed in granulocytes, lymphocytes, platelets, and erythrocytes. Whole transcriptome analysis indicated that EC coculture altered the expression profile of 75 genes in the BM CD34 + cells without impeding the long-term engraftment potential. These findings show that an ex vivo vascular niche is an effective platform for expansion of adult BM HSPCs. Stem Cells Translational Medicine 2017;6:864-876. © 2016 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  12. Endothelial Cells Promote Expansion of Long‐Term Engrafting Marrow Hematopoietic Stem and Progenitor Cells in Primates

    Science.gov (United States)

    Gori, Jennifer L.; Butler, Jason M.; Kunar, Balvir; Poulos, Michael G.; Ginsberg, Michael; Nolan, Daniel J.; Norgaard, Zachary K.; Adair, Jennifer E.; Rafii, Shahin

    2016-01-01

    Abstract Successful expansion of bone marrow (BM) hematopoietic stem and progenitor cells (HSPCs) would benefit many HSPC transplantation and gene therapy/editing applications. However, current expansion technologies have been limited by a loss of multipotency and self‐renewal properties ex vivo. We hypothesized that an ex vivo vascular niche would provide prohematopoietic signals to expand HSPCs while maintaining multipotency and self‐renewal. To test this hypothesis, BM autologous CD34+ cells were expanded in endothelial cell (EC) coculture and transplanted in nonhuman primates. CD34+C38− HSPCs cocultured with ECs expanded up to 17‐fold, with a significant increase in hematopoietic colony‐forming activity compared with cells cultured with cytokines alone (colony‐forming unit‐granulocyte‐erythroid‐macrophage‐monocyte; p < .005). BM CD34+ cells that were transduced with green fluorescent protein lentivirus vector and expanded on ECs engrafted long term with multilineage polyclonal reconstitution. Gene marking was observed in granulocytes, lymphocytes, platelets, and erythrocytes. Whole transcriptome analysis indicated that EC coculture altered the expression profile of 75 genes in the BM CD34+ cells without impeding the long‐term engraftment potential. These findings show that an ex vivo vascular niche is an effective platform for expansion of adult BM HSPCs. Stem Cells Translational Medicine 2017;6:864–876 PMID:28297579

  13. Secondary Disease in Radiation Chimeras

    Energy Technology Data Exchange (ETDEWEB)

    Congdon, C. C. [Biology Division, Oak Ridge National Laboratory, Oak Ridge, TN (United States)

    1969-07-15

    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 LD{sub 50} (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)

  14. Extraembryonic origin of circulating endothelial cells.

    Directory of Open Access Journals (Sweden)

    Luc Pardanaud

    Full Text Available Circulating endothelial cells (CEC are contained in the bone marrow and peripheral blood of adult humans and participate to the revascularization of ischemic tissues. These cells represent attractive targets for cell or gene therapy aimed at improving ischemic revascularization or inhibition of tumor angiogenesis. The embryonic origin of CEC has not been addressed previously. Here we use quail-chick chimeras to study CEC origin and participation to the developing vasculature. CEC are traced with different markers, in particular the QH1 antibody recognizing only quail endothelial cells. Using yolk-sac chimeras, where quail embryos are grafted onto chick yolk sacs and vice-versa, we show that CEC are generated in the yolk sac. These cells are mobilized during wound healing, demonstrating their participation to angiogenic repair processes. Furthermore, we found that the allantois is also able to give rise to CEC in situ. In contrast to the yolk sac and allantois, the embryo proper does not produce CEC. Our results show that CEC exclusively originate from extra-embryonic territories made with splanchnopleural mesoderm and endoderm, while definitive hematopoietic stem cells and endothelial cells are of intra-embryonic origin.

  15. Extraembryonic origin of circulating endothelial cells.

    Science.gov (United States)

    Pardanaud, Luc; Eichmann, Anne

    2011-01-01

    Circulating endothelial cells (CEC) are contained in the bone marrow and peripheral blood of adult humans and participate to the revascularization of ischemic tissues. These cells represent attractive targets for cell or gene therapy aimed at improving ischemic revascularization or inhibition of tumor angiogenesis. The embryonic origin of CEC has not been addressed previously. Here we use quail-chick chimeras to study CEC origin and participation to the developing vasculature. CEC are traced with different markers, in particular the QH1 antibody recognizing only quail endothelial cells. Using yolk-sac chimeras, where quail embryos are grafted onto chick yolk sacs and vice-versa, we show that CEC are generated in the yolk sac. These cells are mobilized during wound healing, demonstrating their participation to angiogenic repair processes. Furthermore, we found that the allantois is also able to give rise to CEC in situ. In contrast to the yolk sac and allantois, the embryo proper does not produce CEC. Our results show that CEC exclusively originate from extra-embryonic territories made with splanchnopleural mesoderm and endoderm, while definitive hematopoietic stem cells and endothelial cells are of intra-embryonic origin.

  16. Cytotoxic T lymphocyte responses in allogeneic radiation bone marrow chimeras. The chimeric host strictly dictates the self-repertoire of Ia-restricted T cells but not H-2K/D-restricted T cells

    International Nuclear Information System (INIS)

    Bradley, S.M.; Kruisbeek, A.M.; Singer, A.

    1982-01-01

    The present report has used fully H-2 allogeneic radiation bone marrow chimeras to assess the role of host restriction elements in determining the self-specificity of Ia- and H-2K/D-restricted T cells that participate in the generation of trinitrophenyl (TNP)-specific cytotoxic T lymphocytes (CTL). It was demonstrated that there exists a stringent requirement for the recognition of host thymic-type Ia determinants, but there exists only a preference for host thymic-type H-2K/D determinants. Indeed, once the stringent requirement for recognition of host Ia determinants was fulfilled, anti-TNP CTL were generated in response to TNP-modified stimulators that expressed either donor-type or host-type H-2K/D determinants. The CTL that were generated in response to TNP-modified donor-type stimulators were shown to be specific for TNP and restricted to the non-thymic H-2K/D determinants of the chimeric donor. Thus, these results demonstrate in a single immune response that the thymic hypothesis accurately predicts the self-specificity expressed by Ia-restricted T cells, but does not fully account for the self-specificity expressed by H-2K/D-restricted T cells. These results are consistent with the concept that H-2K/D-restricted T cells, but not Ia-restricted T cells, can differentiate into functional competence either intrathymically or extra-thymically. The results demonstrate that the generation of anti-TNP CTL responses involve two parallel sets of major histocompatibility complex-restricted cell interactions, an Ia-restricted TH-accessory cell interaction required for TH cell activation, and an H-2K/D-restricted pCTL-stimulator cell interaction required for pCTL stimulation. The interaction between activated TH cells and stimulated pCTL is mediated, at least in part, by nonspecific soluble helper factors

  17. Smallest chimera states

    Science.gov (United States)

    Maistrenko, Yuri; Brezetsky, Serhiy; Jaros, Patrycja; Levchenko, Roman; Kapitaniak, Tomasz

    2017-01-01

    We demonstrate that chimera behavior can be observed in small networks consisting of three identical oscillators, with mutual all-to-all coupling. Three different types of chimeras, characterized by the coexistence of two coherent oscillators and one incoherent oscillator (i.e., rotating with another frequency) have been identified, where the oscillators show periodic (two types) and chaotic (one type) behaviors. Typical bifurcations at the transitions from full synchronization to chimera states and between different types of chimeras have been described. Parameter regions for the chimera states are obtained in the form of Arnold tongues, issued from a singular parameter point. Our analysis suggests that chimera states can be observed in small networks relevant to various real-world systems.

  18. The mathematics behind chimera states

    Science.gov (United States)

    Omel’chenko, O. E.

    2018-05-01

    Chimera states are self-organized spatiotemporal patterns of coexisting coherence and incoherence. We give an overview of the main mathematical methods used in studies of chimera states, focusing on chimera states in spatially extended coupled oscillator systems. We discuss the continuum limit approach to these states, Ott-Antonsen manifold reduction, finite size chimera states, control of chimera states and the influence of system design on the type of chimera state that is observed.

  19. Gargoyles, Grotesques, & Chimeras

    Science.gov (United States)

    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. Endothelial cells and hematopoiesis: a light microscopic study of fetal, normal, and pathologic human bone marrow in plastic-embedded sections.

    Science.gov (United States)

    Islam, A; Glomski, C; Henderson, E S

    1992-07-01

    The origin and morphological identity of hematopoietic progenitor cells, as well as their precursor, the pleuripotential hematopoietic stem cell (HSC), has not been established. Our studies of 2 microns sectioned undecalcified plastic-embedded bone marrow (BM) from healthy human fetuses; normal adults; patients with acute myeloblastic leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic granulocytic leukemia (CGL) in various stages (chronic, accelerated, acute blastic phase, and after autografting); and patients recovering from therapy-induced marrow hypoplasia suggest that proliferative hematopoietic zones exist near the endosteum (endosteal marrow) and the vascular endothelium (capillary and sinus-lining endothelium) and a maturational zone distal to these regions. In some of these areas, morphologically recognizable hematopoietic cells were seen and interpreted as emerging and maturing in a sequential progression, suggesting an origin from the endosteal or endothelial progenitors. In other loci, early hematopoietic cells were seen in close contact with the endosteal or vascular endothelial (VE) cells. This latter relationship suggested that these areas of cellular contact were important and represented sites of cell to cell interaction that may be associated with the liberation of growth factors by endosteal and endothelial cells and their action on hematopoietic progenitor cells. Following treatment-induced hypoplasia, the endosteal and VE cells were seen to modulate, transform, and migrate into the surrounding empty and edematous marrow space as fibroblasts. Later, as hemopoietic regeneration began, clusters of regenerating hematopoietic cells were seen adjacent to bone trabecule (BT) and near the vascular endothelium. We postulate that endosteal and VE cells are the equivalent of embryonal-stage, undifferentiated mesenchyme and, under the appropriate regulatory influence, are capable of modulation and transformation (differentiation) into stromal

  1. Chimera states in bursting neurons

    OpenAIRE

    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...

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

    International Nuclear Information System (INIS)

    Iwabuchi, C.; Iwabuchi, K.; Kobayashi, S.; Ogasawara, K.; Negishi, I.; Wang, B.Y.; Wambua, P.P.; Arase, H.; Fukushi, N.; Itoh, Y.

    1991-01-01

    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

  3. Origin of hemopoietic stromal progenitor cells in chimeras

    International Nuclear Information System (INIS)

    Chertkov, J.L.; Drize, N.J.; Gurevitch, O.A.; Samoylova, R.S.

    1985-01-01

    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

  4. The effect of two novel amino acid-coated magnetic nanoparticles on survival in vascular endothelial cells, bone marrow stromal cells, and macrophages

    Science.gov (United States)

    Wu, Qinghua; Meng, Ning; Zhang, Yanru; Han, Lei; Su, Le; Zhao, Jing; Zhang, Shangli; Zhang, Yun; Zhao, Baoxiang; Miao, Junying

    2014-09-01

    Magnetic nanoparticles (MNPs) have been popularly used in many fields. Recently, many kinds of MNPs are modified as new absorbents, which have attracted considerable attention and are promising to be applied in waste water. In our previous study, we synthesized two novel MNPs surface-coated with glycine or lysine, which could efficiently remove many anionic and cationic dyes under severe conditions. It should be considered that MNP residues in water may exert some side effects on human health. In the present study, we evaluated the potential nanotoxicity of MNPs in human endothelial cells, macrophages, and rat bone marrow stromal cells. The results showed that the two kinds of nanoparticles were consistently absorbed into the cell cytoplasm. The concentration of MNPs@Gly that could distinctly decrease survival was 15 μg/ml in human umbilical vascular endothelial cells (HUVECs) or bone marrow stromal cells (BMSCs) and 10 μg/ml in macrophages. While the concentration of MNPs@Lys that obviously reduced viability was 15 μg/ml in HUVECs or macrophages and 50 μg/ml in BMSCs. Furthermore, cell nucleus staining and cell integrity assay indicated that the nanoparticles induced cell apoptosis, but not necrosis even at a high concentration. Altogether, these data suggest that the amino acid-coated magnetic nanoparticles exert relatively high cytotoxicity. By contrast, lysine-coated magnetic nanoparticles are more secure than glycine-coated magnetic nanoparticles.

  5. Resistance to BN myelogenous leukemia in rat radiation chimeras

    International Nuclear Information System (INIS)

    Singer, D.E.; Haynor, D.R.; Williams, R.M

    1980-01-01

    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)

  6. Platelet released growth factors boost expansion of bone marrow derived CD34(+) and CD133(+) endothelial progenitor cells for autologous grafting.

    Science.gov (United States)

    Lippross, Sebastian; Loibl, Markus; Hoppe, Sven; Meury, Thomas; Benneker, Lorin; Alini, Mauro; Verrier, Sophie

    2011-01-01

    Stem cell based autologous grafting has recently gained mayor interest in various surgical fields for the treatment of extensive tissue defects. CD34(+) and CD133(+) cells that can be isolated from the pool of bone marrow mononuclear cells (BMC) are capable of differentiating into mature endothelial cells in vivo. These endothelial progenitor cells (EPC) are believed to represent a major portion of the angiogenic regenerative cells that are released from bone marrow when tissue injury has occurred. In recent years tissue engineers increasingly looked at the process of vessel neoformation because of its major importance for successful cell grafting to replace damaged tissue. Up to now one of the greatest problems preventing a clinical application is the large scale of expansion that is required for such purpose. We established a method to effectively enhance the expansion of CD34(+) and CD133(+) cells by the use of platelet-released growth factors (PRGF) as a media supplement. PRGF were prepared from thrombocyte concentrates and used as a media supplement to iscove's modified dulbecco's media (IMDM). EPC were immunomagnetically separated from human bone morrow monocyte cells and cultured in IMDM + 10% fetal calf serum (FCS), IMDM + 5%, FCS + 5% PRGF and IMDM + 10% PRGF. We clearly demonstrate a statistically significant higher and faster cell proliferation rate at 7, 14, 21, and 28 days of culture when both PRGF and FCS were added to the medium as opposed to 10% FCS or 10% PRGF alone. The addition of 10% PRGF to IMDM in the absence of FCS leads to a growth arrest from day 14 on. In histochemical, immunocytochemical, and gene-expression analysis we showed that angiogenic and precursor markers of CD34(+) and CD133(+) cells are maintained during long-term culture. In summary, we established a protocol to boost the expansion of CD34(+) and CD133(+) cells. Thereby we provide a technical step towards the clinical application of autologous stem cell

  7. Amplitude chimeras and chimera death in dynamical networks

    International Nuclear Information System (INIS)

    Zakharova, Anna; Kapeller, Marie; Schöll, Eckehard

    2016-01-01

    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 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. (paper)

  8. Symmetries of Chimera States

    Science.gov (United States)

    Kemeth, Felix P.; Haugland, Sindre W.; Krischer, Katharina

    2018-05-01

    Symmetry broken states arise naturally in oscillatory networks. In this Letter, we investigate chaotic attractors in an ensemble of four mean-coupled Stuart-Landau oscillators with two oscillators being synchronized. We report that these states with partially broken symmetry, so-called chimera states, have different setwise symmetries in the incoherent oscillators, and in particular, some are and some are not invariant under a permutation symmetry on average. This allows for a classification of different chimera states in small networks. We conclude our report with a discussion of related states in spatially extended systems, which seem to inherit the symmetry properties of their counterparts in small networks.

  9. Dynamics of bone marrow-derived endothelial progenitor cell/mesenchymal stem cell interaction in co-culture and its implications in angiogenesis

    International Nuclear Information System (INIS)

    Aguirre, A.; Planell, J.A.; Engel, E.

    2010-01-01

    Research highlights: → BM-EPCs and MSCs establish complex, self-organizing structures in co-culture. → Co-culture decreases proliferation by cellular self-regulatory mechanisms. → Co-cultured cells present an activated proangiogenic phenotype. → qRT-PCR and cluster analysis identify new target genes playing important roles. -- Abstract: Tissue engineering aims to regenerate tissues and organs by using cell and biomaterial-based approaches. One of the current challenges in the field is to promote proper vascularization in the implant to prevent cell death and promote host integration. Bone marrow endothelial progenitor cells (BM-EPCs) and mesenchymal stem cells (MSCs) are bone marrow resident stem cells widely employed for proangiogenic applications. In vivo, they are likely to interact frequently both in the bone marrow and at sites of injury. In this study, the physical and biochemical interactions between BM-EPCs and MSCs in an in vitro co-culture system were investigated to further clarify their roles in vascularization. BM-EPC/MSC co-cultures established close cell-cell contacts soon after seeding and self-assembled to form elongated structures at 3 days. Besides direct contact, cells also exhibited vesicle transport phenomena. When co-cultured in Matrigel, tube formation was greatly enhanced even in serum-starved, growth factor free medium. Both MSCs and BM-EPCs contributed to these tubes. However, cell proliferation was greatly reduced in co-culture and morphological differences were observed. Gene expression and cluster analysis for wide panel of angiogenesis-related transcripts demonstrated up-regulation of angiogenic markers but down-regulation of many other cytokines. These data suggest that cross-talk occurs in between BM-EPCs and MSCs through paracrine and direct cell contact mechanisms leading to modulation of the angiogenic response.

  10. Chimera: Experiencing Language Arts.

    Science.gov (United States)

    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)

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

    International Nuclear Information System (INIS)

    Storb, R.; Tsoi, M.S.; Weiden, P.L.; Graham, T.C.; Thomas, E.D.

    1976-01-01

    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

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

    International Nuclear Information System (INIS)

    Gengozian, N.; Urso, P.

    1976-01-01

    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, CD2F 1 → C3BF 1 , 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

  13. Electroacupuncture modulates stromal cell-derived factor-1α expression and mobilization of bone marrow endothelial progenitor cells in focal cerebral ischemia/reperfusion model rats.

    Science.gov (United States)

    Xie, Chenchen; Gao, Xiang; Luo, Yong; Pang, Yueshan; Li, Man

    2016-10-01

    Stromal cell-derived factor-1α(SDF-1α) plays a crucial role in regulating the mobilization, migration and homing of endothelial progenitor cells(EPCs). Electroacupuncture(EA), a modern version of Traditional Chinese Medicine, can improve neurological recovery and angiogenesis in cerebral ischemic area. This study aimed to investigate the effects of electroacupuncture(EA) on the mobilization and migration of bone marrow EPCs and neurological functional recovery in rats model after focal cerebral ischemia/reperfusion and the potentially involved mechanisms. Sprague-Dawley rats received filament occlusion of the right middle cerebral artery for 2h followed by reperfusion for 12h, 1d, 2d, 3d, 7d respectively. Rats were randomly divided into sham group, model group and EA group. After 2h of the reperfusion, EA was given at the "Baihui" (GV 20)/Siguan ("Hegu" (LI 4)/"Taichong" (LR 3)) acupoints in the EA group. Modified neurological severity score (mNSS) was used to assess the neurological functional recovery. EPCs number and SDF-1α level in bone marrow(BM) and peripheral blood(PB) were detected by using fluorescence-activated cell sorting (FACS) analysis and quantitative real time polymerase chain reaction (qRT-PCR) respectively. An mNSS test showed that EA treatment significantly improved the neurological functional outcome. EPCs number in PB and BM were obviously increased in the EA group. After cerebral ischemia, the SDF-1α level was decreased in BM while it was increased in PB, which implied a gradient of SDF-1α among BM and PB after ischemia. It suggested that the forming of SDF-1α concentration gradient can induce the mobilization and homing of EPCs. Eletroacupuncture as a treatment can accelerate and increase the forming of SDF-1α concentration gradient to further induce the mobilization of EPCs and angiogenesis in ischemic brain and improve the neurological function recovery. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Chimera Grid Tools

    Science.gov (United States)

    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.

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

    International Nuclear Information System (INIS)

    Boyd, A.D.; Spencer, F.C.; Hirose, H.; Engelman, R.M.; Cannon, F.D.; Ferrebee, J.W.; Rapaport, F.T.

    1975-01-01

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

    International Nuclear Information System (INIS)

    Rayfield, L.S.; Brent, L.

    1983-01-01

    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

  17. Vascular endothelial growth factor regulates melanoma cell adhesion and growth in the bone marrow microenvironment via tumor cyclooxygenase-2

    Directory of Open Access Journals (Sweden)

    Crende Olatz

    2011-08-01

    Full Text Available Abstract Background Human melanoma frequently colonizes bone marrow (BM since its earliest stage of systemic dissemination, prior to clinical metastasis occurrence. However, how melanoma cell adhesion and proliferation mechanisms are regulated within bone marrow stromal cell (BMSC microenvironment remain unclear. Consistent with the prometastatic role of inflammatory and angiogenic factors, several studies have reported elevated levels of cyclooxygenase-2 (COX-2 in melanoma although its pathogenic role in bone marrow melanoma metastasis is unknown. Methods Herein we analyzed the effect of cyclooxygenase-2 (COX-2 inhibitor celecoxib in a model of generalized BM dissemination of left cardiac ventricle-injected B16 melanoma (B16M cells into healthy and bacterial endotoxin lipopolysaccharide (LPS-pretreated mice to induce inflammation. In addition, B16M and human A375 melanoma (A375M cells were exposed to conditioned media from basal and LPS-treated primary cultured murine and human BMSCs, and the contribution of COX-2 to the adhesion and proliferation of melanoma cells was also studied. Results Mice given one single intravenous injection of LPS 6 hour prior to cancer cells significantly increased B16M metastasis in BM compared to untreated mice; however, administration of oral celecoxib reduced BM metastasis incidence and volume in healthy mice, and almost completely abrogated LPS-dependent melanoma metastases. In vitro, untreated and LPS-treated murine and human BMSC-conditioned medium (CM increased VCAM-1-dependent BMSC adherence and proliferation of B16M and A375M cells, respectively, as compared to basal medium-treated melanoma cells. Addition of celecoxib to both B16M and A375M cells abolished adhesion and proliferation increments induced by BMSC-CM. TNFα and VEGF secretion increased in the supernatant of LPS-treated BMSCs; however, anti-VEGF neutralizing antibodies added to B16M and A375M cells prior to LPS-treated BMSC-CM resulted in a

  18. Vascular endothelial growth factor/bone morphogenetic protein-2 bone marrow combined modification of the mesenchymal stem cells to repair the avascular necrosis of the femoral head

    Science.gov (United States)

    Ma, Xiao-Wei; Cui, Da-Ping; Zhao, De-Wei

    2015-01-01

    Vascular endothelial cell growth factor (VEGF) combined with bone morphogenetic protein (BMP) was used to repair avascular necrosis of the femoral head, which can maintain the osteogenic phenotype of seed cells, and effectively secrete VEGF and BMP-2, and effectively promote blood vessel regeneration and contribute to formation and revascularization of tissue engineered bone tissues. To observe the therapeutic effect on the treatment of avascular necrosis of the femoral head by using bone marrow mesenchymal stem cells (BMSCs) modified by VEGF-165 and BMP-2 in vitro. The models were avascular necrosis of femoral head of rabbits on right leg. There groups were single core decompression group, core decompression + BMSCs group, core decompression + VEGF-165/BMP-2 transfect BMSCs group. Necrotic bone was cleared out under arthroscope. Arthroscopic observation demonstrated that necrotic bone was cleared out in each group, and fresh blood flowed out. Histomorphology determination showed that blood vessel number and new bone area in the repair region were significantly greater at various time points following transplantation in the core decompression + VEGF-165/BMP-2 transfect BMSCs group compared with single core decompression group and core decompression + BMSCs group (P < 0.05). These suggested that VEGF-165/BMP-2 gene transfection strengthened osteogenic effects of BMSCs, elevated number and quality of new bones and accelerated the repair of osteonecrosis of the femoral head. PMID:26629044

  19. Autologous bone-marrow mesenchymal stem cell implantation and endothelial function in a rabbit ischemic limb model.

    Directory of Open Access Journals (Sweden)

    Shinsuke Mikami

    Full Text Available BACKGROUND: The purpose of this study was to determine whether autologous mesenchymal stem cells (MSCs implantation improves endothelial dysfunction in a rabbit ischemic limb model. METHODS: We evaluated the effect of MSC implantation on limb blood flow (LBF responses to acetylcholine (ACh, an endothelium-dependent vasodilator, and sodium nitroprusside (SNP, an endothelium-independent vasodilator, in rabbits with limb ischemia in which cultured MSCs were implanted (n = 20 or saline was injected as a control group (n = 20. LBF was measured using an electromagnetic flowmeter. A total of 10(6 MSCs were implanted into each ischemic limb. RESULTS: Histological sections of ischemic muscle showed that capillary index (capillary/muscle fiber was greater in the MSC implantation group than in the control group. Laser Doppler blood perfusion index was significantly increased in the MSC implantation group compared with that in the control group. LBF response to ACh was greater in the MSC group than in the control group. After administration of N(G-nitro-L-arginine, a nitric oxide synthase inhibitor, LBF response to ACh was similar in the MSC implantation group and control group. Vasodilatory effects of SNP in the two groups were similar. CONCLUSIONS: These findings suggest that MSC implantation induces angiogenesis and augments endothelium-dependent vasodilation in a rabbit ischemic model through an increase in nitric oxide production.

  20. Recurrence quantification analysis of chimera states

    International Nuclear Information System (INIS)

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

    2015-01-01

    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. - 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

  1. Recurrence quantification analysis of chimera states

    Energy Technology Data Exchange (ETDEWEB)

    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.

  2. Multiple scroll wave chimera states

    Science.gov (United States)

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

    2017-06-01

    We report the appearance of three-dimensional (3D) multiheaded chimera states that display cascades of self-organized spatiotemporal patterns of coexisting coherence and incoherence. We demonstrate that the number of incoherent chimera domains can grow additively under appropriate variations of the system parameters generating thereby head-adding cascades of the scroll wave chimeras. The phenomenon is derived for the Kuramoto model of N 3 identical phase oscillators placed in the unit 3D cube with periodic boundary conditions, parameters being the coupling radius r and phase lag α. To obtain the multiheaded chimeras, we perform the so-called `cloning procedure' as follows: choose a sample single-headed 3D chimera state, make appropriate scale transformation, and put some number of copies of them into the unit cube. After that, start numerical simulations with slightly perturbed initial conditions and continue them for a sufficiently long time to confirm or reject the state existence and stability. In this way it is found, that multiple scroll wave chimeras including those with incoherent rolls, Hopf links and trefoil knots admit this sort of multiheaded regeneration. On the other hand, multiple 3D chimeras without spiral rotations, like coherent and incoherent balls, tubes, crosses, and layers appear to be unstable and are destroyed rather fast even for arbitrarily small initial perturbations.

  3. Chemokine receptors CXCR2 and CX3CR1 differentially regulate functional responses of bone-marrow endothelial progenitors during atherosclerotic plaque regression

    Science.gov (United States)

    Herlea-Pana, Oana; Yao, Longbiao; Heuser-Baker, Janet; Wang, Qiongxin; Wang, Qilong; Georgescu, Constantin; Zou, Ming-Hui; Barlic-Dicen, Jana

    2015-01-01

    Aims Atherosclerosis manifests itself as arterial plaques, which lead to heart attacks or stroke. Treatments supporting plaque regression are therefore aggressively pursued. Studies conducted in models in which hypercholesterolaemia is reversible, such as the Reversa mouse model we have employed in the current studies, will be instrumental for the development of such interventions. Using this model, we have shown that advanced atherosclerosis regression occurs when lipid lowering is used in combination with bone-marrow endothelial progenitor cell (EPC) treatment. However, it remains unclear how EPCs home to regressing plaques and how they augment atherosclerosis reversal. Here we identify molecules that support functional responses of EPCs during plaque resolution. Methods and results Chemokines CXCL1 and CX3CL1 were detected in the vascular wall of atheroregressing Reversa mice, and their cognate receptors CXCR2 and CX3CR1 were observed on adoptively transferred EPCs in circulation. We tested whether CXCL1–CXCR2 and CX3CL1–CX3CR1 axes regulate functional responses of EPCs during plaque reversal. We show that pharmacological inhibition of CXCR2 or CX3CR1, or genetic inactivation of these two chemokine receptors interfered with EPC-mediated advanced atherosclerosis regression. We also demonstrate that CXCR2 directs EPCs to regressing plaques while CX3CR1 controls a paracrine function(s) of these cells. Conclusion CXCR2 and CX3CR1 differentially regulate EPC functional responses during atheroregression. Our study improves understanding of how chemokines and chemokine receptors regulate plaque resolution, which could determine the effectiveness of interventions reducing complications of atherosclerosis. PMID:25765938

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

    International Nuclear Information System (INIS)

    Mojzhess, T.G.; Prigozhina, E.L.

    1976-01-01

    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

  5. Enstore with Chimera namespace provider

    International Nuclear Information System (INIS)

    Litvintsev, Dmitry; Moibenko, Alexander; Oleynik, Gene; Zalokar, Michael

    2012-01-01

    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.

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

    International Nuclear Information System (INIS)

    Rueedi, E.S.; Sykes, M.; Ildstad, S.T.; Chester, C.H.; Althage, A.; Hengartner, H.; Sachs, D.H.; Zinkernagel, R.M.

    1989-01-01

    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

  7. Inducing and destruction of chimeras and chimera-like states by an external harmonic force

    Science.gov (United States)

    Shepelev, I. A.; Vadivasova, T. E.

    2018-03-01

    We study the phenomena of chimera destruction and inducing of chimera-like states in an ensemble of nonlocally coupled chaotic Rössler oscillators under an external harmonic force. The localized harmonic influence can lead to both destruction and changing of the spatial topology of chimeras. At the same time this influence can cause the emergence of stable chimera-like states (induced chimeras) for the regime of partial coherent chaos. Induced chimeras are also observed for the global influence. We show the possibility of controlling the chimera-like state topology by varying the parameters of localized external harmonic influence.

  8. Generalized synchronization between chimera states

    Science.gov (United States)

    Andrzejak, Ralph G.; Ruzzene, Giulia; Malvestio, Irene

    2017-05-01

    Networks of coupled oscillators in chimera states are characterized by an intriguing interplay of synchronous and asynchronous motion. While chimera states were initially discovered in mathematical model systems, there is growing experimental and conceptual evidence that they manifest themselves also in natural and man-made networks. In real-world systems, however, synchronization and desynchronization are not only important within individual networks but also across different interacting networks. It is therefore essential to investigate if chimera states can be synchronized across networks. To address this open problem, we use the classical setting of ring networks of non-locally coupled identical phase oscillators. We apply diffusive drive-response couplings between pairs of such networks that individually show chimera states when there is no coupling between them. The drive and response networks are either identical or they differ by a variable mismatch in their phase lag parameters. In both cases, already for weak couplings, the coherent domain of the response network aligns its position to the one of the driver networks. For identical networks, a sufficiently strong coupling leads to identical synchronization between the drive and response. For non-identical networks, we use the auxiliary system approach to demonstrate that generalized synchronization is established instead. In this case, the response network continues to show a chimera dynamics which however remains distinct from the one of the driver. Hence, segregated synchronized and desynchronized domains in individual networks congregate in generalized synchronization across networks.

  9. Chimera states in three dimensions

    International Nuclear Information System (INIS)

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

    2015-01-01

    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. (paper)

  10. Petascale supernova simulation with CHIMERA

    Energy Technology Data Exchange (ETDEWEB)

    Messer, O E B [National Center for Computational Sciences, Oak Ridge National Laboratory, Oak Ridge, TN 37831-6008 (United States); Bruenn, S W [Department of Physics, Florida Atlantic University, 777 W Glades Road, Boca Raton, FL 33431-0991 (United States); Blondin, J M [Department of Physics, North Carolina State University, Raleigh, NC 27695-8202 (United States); Hix, W R [Physics Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831-6354 (United States); Mezzacappa, A [Physics Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831-6354 (United States); Dirk, C J [Department of Physics, Florida Atlantic University, 777 W Glades Road, Boca Raton, FL 33431-0991 (United States)

    2007-07-15

    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.

  11. Lessons from Interspecies Mammalian Chimeras.

    Science.gov (United States)

    Suchy, Fabian; Nakauchi, Hiromitsu

    2017-10-06

    As chimeras transform from beasts of Greek mythology into tools of contemporary bioscience, secrets of developmental biology and evolutionary divergence are being revealed. Recent advances in stem cell biology and interspecies chimerism have generated new models with extensive basic and translational applications, including generation of transplantable, patient-specific organs.

  12. Chimera States in Neural Oscillators

    Science.gov (United States)

    Bahar, Sonya; Glaze, Tera

    2014-03-01

    Chimera states have recently been explored both theoretically and experimentally, in various coupled nonlinear oscillators, ranging from phase-oscillator models to coupled chemical reactions. In a chimera state, both coherent and incoherent (or synchronized and desynchronized) states occur simultaneously in populations of identical oscillators. We investigate chimera behavior in a population of neural oscillators using the Huber-Braun model, a Hodgkin-Huxley-like model originally developed to characterize the temperature-dependent bursting behavior of mammalian cold receptors. One population of neurons is allowed to synchronize, with each neuron receiving input from all the others in its group (global within-group coupling). Subsequently, a second population of identical neurons is placed under an identical global within-group coupling, and the two populations are also coupled to each other (between-group coupling). For certain values of the coupling constants, the neurons in the two populations exhibit radically different synchronization behavior. We will discuss the range of chimera activity in the model, and discuss its implications for actual neural activity, such as unihemispheric sleep.

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

    International Nuclear Information System (INIS)

    Urso, P.; Gengozian, N.

    1977-01-01

    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

  14. Recent results of CHIMERA activity

    Directory of Open Access Journals (Sweden)

    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.

  15. Mobility-induced persistent chimera states

    Science.gov (United States)

    Petrungaro, Gabriela; Uriu, Koichiro; Morelli, Luis G.

    2017-12-01

    We study the dynamics of mobile, locally coupled identical oscillators in the presence of coupling delays. We find different kinds of chimera states in which coherent in-phase and antiphase domains coexist with incoherent domains. These chimera states are dynamic and can persist for long times for intermediate mobility values. We discuss the mechanisms leading to the formation of these chimera states in different mobility regimes. This finding could be relevant for natural and technological systems composed of mobile communicating agents.

  16. The effect of peripheral lymphoid cells on the incidence of lethal graft versus host disease following allogeneic mouse bone marrow transplantation

    International Nuclear Information System (INIS)

    Almaraz, R.; Ballinger, W.; Sachs, D.H.; Rosenberg, S.A.

    1983-01-01

    Experiments were performed to study the role of circulating lymphoid cells in the incidence of lethal graft versus host disease (GVHD) in radiation-induced fully allogeneic mouse chimeras. The incidence of GVHD was reduced significantly in BALB/c leads to C57BL/6 radiation chimeras if bone marrow donors were exsanguinated immediately prior to marrow harvest. Chimeras resulting from the injection of bone marrow from bled donors exhibited only donor cells in spleen, bone marrow and peripheral blood and normal levels of Thy 1+ and Ia+ cells were found in each of these lymphoid compartments. The addition of as few as 3 X 10(4) peripheral mononuclear cells to the marrow from exsanguinated donors uniformly led to lethal GVHD. 51 Cr-labeled cell traffic studies revealed that prior exsanguination of marrow donors led to about a 70% reduction in the number of circulating mononuclear cells contaminating the bone marrow at the time of marrow harvest. This decrease in contaminating peripheral cells was calculated to be in the appropriate range to account for the decreased GVHD seen when marrow from exsanguinated donors was used. It thus appears that peripheral cells contaminating marrow can be an important factor in causing lethal GVHD in allogeneic radiation chimeras. These results raise the possibility that the fulminant GVHD seen in human marrow transplantation is in part due to the major contamination of bone marrow with peripheral blood that results from the techniques currently used for human bone marrow harvest

  17. Effect of peripheral lymphoid cells on the incidence of lethal graft versus host disease following allogeneic mouse bone marrow transplantation

    International Nuclear Information System (INIS)

    Almaraz, R.; Ballinger, W.; Sachs, D.H.; Rosenberg, S.A.

    1983-01-01

    Experiments were performed to study the role of circulating lymphoid cells in the incidence of lethal graft versus host disease (GVHD) in radiation-induced fully allogeneic mouse chimeras. The incidence of GVHD was reduced significantly in BALB/c leads to C57BL/6 radiation chimeras if bone marrow donors were exsanguinated immediately prior to marrow harvest. Chimeras resulting from the injection of bone marrow from bled donors exhibited only donor cells in spleen, bone marrow and peripheral blood and normal levels of Thy 1+ and Ia+ cells were found in each of these lymphoid compartments. The addition of as few as 3 X 10(4) peripheral mononuclear cells to the marrow from exsanguinated donors uniformly led to lethal GVHD. 51 Cr-labeled cell traffic studies revealed that prior exsanguination of marrow donors led to about a 70% reduction in the number of circulating mononuclear cells contaminating the bone marrow at the time of marrow harvest. This decrease in contaminating peripheral cells was calculated to be in the appropriate range to account for the decreased GVHD seen when marrow from exsanguinated donors was used. It thus appears that peripheral cells contaminating marrow can be an important factor in causing lethal GVHD in allogeneic radiation chimeras

  18. Bone marrow aspiration

    Science.gov (United States)

    Iliac crest tap; Sternal tap; Leukemia - bone marrow aspiration; Aplastic anemia - bone marrow aspiration; Myelodysplastic syndrome - bone marrow aspiration; Thrombocytopenia - bone marrow aspiration; Myelofibrosis - bone marrow aspiration

  19. Periclinal chimera technique: new plant breeding approach.

    Science.gov (United States)

    Gakpetor, P M; Mohammed, H; Moreti, D; Nassar, N M A

    2017-09-21

    Plant interspecific periclinal chimeras are a mosaic formed by tissues from two species. They are manipulated here as an efficient plant breeding tool for cassava root yields. In this study, plants synthesized from two chimeras, designated as chimera 2 and chimera 4, were characterized morphologically and cytologically to unravel the origin of their tissue layers (L2 and L3). Root yield of the two chimeras was also evaluated. Chimera 2 that was developed from graft union between Manihot fortalezensis (F) as scion and M. esculenta (E) as rootstock and the same in chimera 4 was developed from grafting triploid cassava cultivar (2n = 54) (C) as scion and M. pohlii (P) (2n = 36) as rootstock. A new method of inducing interspecific chimeras without using hormones was also tested in this study. Five combinations between four cassava cultivars on one side and M. fortalezensis and an interspecific hybrid (M. glaziovii x M. esculenta) on the other side were experimented to determine compatibility between the parents. Wild species always gave L2 and L3, independent of being used as rootstock or scion. L3 is responsible for producing pericycle. Thus, its performance was different in each chimera due to specific epigenetic interaction. Of 48 grafts, it was obtained one chimera giving a percentage of 2.1% that is little lower than using hormones but much efficient to use. Chimera induction efficiency in this investigation was the same when using hormones. Thus, our new, less labor, and more cost-effective technique is as much efficient as hormones and is much potential to employ as an effective plant breeding method boosting cassava root yield.

  20. Radiation-induced mouse chimeras: a cellular analysis of the major lymphoid compartments, factors affecting lethal graft versus host disease and host-tumor interactions

    International Nuclear Information System (INIS)

    Almaraz, R.

    1981-01-01

    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

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

    International Nuclear Information System (INIS)

    Lannin, D.R.; Yu, S.; McKhann, C.F.

    1982-01-01

    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 F 1 → 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) F 1 hybrid bone marrow. The F 1 → C3H chimera but not the F 1 → 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 F 1 → C57BL/6 chimera but not the F 1 → 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

  2. Chimera states in mechanical oscillator networks

    DEFF Research Database (Denmark)

    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...... of whether chimeras are indeed characteristic of 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 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-organization observed...

  3. Refining the intrinsic chimera flap: a review.

    Science.gov (United States)

    Agarwal, Jayant P; Agarwal, Shailesh; Adler, Neta; Gottlieb, Lawrence J

    2009-10-01

    Reconstruction of complex tissue deficiencies in which each missing component is in a different spatial relationship to each other can be particularly challenging, especially in patients with limited recipient vessels. The chimera flap design is uniquely suited to reconstruct these deformities. Chimera flaps have been previously defined in many ways with 2 main categories: prefabricated or intrinsic. Herein we attempt to clarify the definition of a true intrinsic chimeric flap and provide examples of how these constructs provide a method for reconstruction of complex defects. The versatility of the intrinsic chimera flap and its procurement from 7 different vascular systems is described. A clarification of the definition of a true intrinsic chimera flap is described. In addition, construction of flaps from the lateral femoral circumflex, deep circumflex iliac, inferior gluteal, peroneal, subscapular, thoracodorsal, and radial arterial systems is described to showcase the versatility of these chimera flaps. A true intrinsic chimera flap must consist of more than a single tissue type. Each of the tissue components receives its blood flow from separate vascular branches or perforators that are connected to a single vascular source. These vascular branches must be of appropriate length to allow for insetting with 3-dimensional spatial freedom. There are a multitude of sites from which true intrinsic chimera flaps may be harvested.

  4. Solvable model for chimera states of coupled oscillators.

    Science.gov (United States)

    Abrams, Daniel M; Mirollo, Rennie; Strogatz, Steven H; Wiley, Daniel A

    2008-08-22

    Networks of identical, symmetrically coupled oscillators can spontaneously split into synchronized and desynchronized subpopulations. Such chimera states were discovered in 2002, but are not well understood theoretically. Here we obtain the first exact results about the stability, dynamics, and bifurcations of chimera states by analyzing a minimal model consisting of two interacting populations of oscillators. Along with a completely synchronous state, the system displays stable chimeras, breathing chimeras, and saddle-node, Hopf, and homoclinic bifurcations of chimeras.

  5. The Dependence of Chimera States on Initial Conditions

    International Nuclear Information System (INIS)

    Feng Yue-E; Li Hai-Hong

    2015-01-01

    A chimera state consisting of both coherent and incoherent groups is a fascinating spatial pattern in non-locally coupled identical oscillators. It is thought that random initial conditions hardly evolve to chimera states. In this work, we study the dependence of chimera states on initial conditions. We show that random initial conditions may lead to chimera states and the chance of realizing chimera states becomes increasing when the model parameters are moving away from the boundary of their stable regime. (paper)

  6. Synthesis of periclinal chimera in cassava.

    Science.gov (United States)

    Nassar, N M A; Bomfim, N

    2013-02-27

    We provide the first report on the synthesis of a very productive interspecific periclinal chimera of cassava, with large and edible roots. The epidermal tissue of the chimera was formed by the cultivated species Manihot esculenta (E), and the subepidermis and internal tissue were formed by the wild species, Manihot fortalezensis (F). We used cytogenetics and morphological analyses to determine the origins of all tissues. These results may offer potential for the development of new lines for crop improvement based on the use of chimera composed of different combinations of wild species and cultivars.

  7. PyChimera: use UCSF Chimera modules in any Python 2.7 project.

    Science.gov (United States)

    Rodríguez-Guerra Pedregal, Jaime; Maréchal, Jean-Didier

    2018-05-15

    UCSF Chimera is a powerful visualization tool remarkably present in the computational chemistry and structural biology communities. Built on a C++ core wrapped under a Python 2.7 environment, one could expect to easily import UCSF Chimera's arsenal of resources in custom scripts or software projects. Nonetheless, this is not readily possible if the script is not executed within UCSF Chimera due to the isolation of the platform. UCSF ChimeraX, successor to the original Chimera, partially solves the problem but yet major upgrades need to be undergone so that this updated version can offer all UCSF Chimera features. PyChimera has been developed to overcome these limitations and provide access to the UCSF Chimera codebase from any Python 2.7 interpreter, including interactive programming with tools like IPython and Jupyter Notebooks, making it easier to use with additional third-party software. PyChimera is LGPL-licensed and available at https://github.com/insilichem/pychimera. jaime.rodriguezguerra@uab.cat or jeandidier.marechal@uab.cat. Supplementary data are available at Bioinformatics online.

  8. Chimeras

    OpenAIRE

    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.

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

    International Nuclear Information System (INIS)

    Lattime, E.C.; Gershon, H.E.; Stutman, O.

    1980-01-01

    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

  10. Generation of axolotl hematopoietic chimeras

    Directory of Open Access Journals (Sweden)

    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.

  11. Intermittent chaotic chimeras for coupled rotators

    DEFF Research Database (Denmark)

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

    2015-01-01

    Two 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 other...

  12. Quantum walk on a chimera graph

    Science.gov (United States)

    Xu, Shu; Sun, Xiangxiang; Wu, Jizhou; Zhang, Wei-Wei; Arshed, Nigum; Sanders, Barry C.

    2018-05-01

    We analyse a continuous-time quantum walk on a chimera graph, which is a graph of choice for designing quantum annealers, and we discover beautiful quantum walk features such as localization that starkly distinguishes classical from quantum behaviour. Motivated by technological thrusts, we study continuous-time quantum walk on enhanced variants of the chimera graph and on diminished chimera graph with a random removal of vertices. We explain the quantum walk by constructing a generating set for a suitable subgroup of graph isomorphisms and corresponding symmetry operators that commute with the quantum walk Hamiltonian; the Hamiltonian and these symmetry operators provide a complete set of labels for the spectrum and the stationary states. Our quantum walk characterization of the chimera graph and its variants yields valuable insights into graphs used for designing quantum-annealers.

  13. Non-identical multiplexing promotes chimera states

    Science.gov (United States)

    Ghosh, Saptarshi; Zakharova, Anna; Jalan, Sarika

    2018-01-01

    We present the emergence of chimeras, a state referring to coexistence of partly coherent, partly incoherent dynamics in networks of identical oscillators, in a multiplex network consisting of two non-identical layers which are interconnected. We demonstrate that the parameter range displaying the chimera state in the homogeneous first layer of the multiplex networks can be tuned by changing the link density or connection architecture of the same nodes in the second layer. We focus on the impact of the interconnected second layer on the enlargement or shrinking of the coupling regime for which chimeras are displayed in the homogeneous first layer. We find that a denser homogeneous second layer promotes chimera in a sparse first layer, where chimeras do not occur in isolation. Furthermore, while a dense connection density is required for the second layer if it is homogeneous, this is not true if the second layer is inhomogeneous. We demonstrate that a sparse inhomogeneous second layer which is common in real-world complex systems can promote chimera states in a sparse homogeneous first layer.

  14. Enhancing UCSF Chimera through web services.

    Science.gov (United States)

    Huang, Conrad C; Meng, Elaine C; Morris, John H; Pettersen, Eric F; Ferrin, Thomas E

    2014-07-01

    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 streamlining access to web services, including the entire job submission, monitoring and retrieval process, Chimera makes it simpler for users to focus on their science projects rather than data manipulation. Chimera uses Opal, a toolkit for wrapping scientific applications as web services, to provide scalable and transparent access to several popular software packages. We illustrate Chimera's use of web services with an example workflow that interleaves use of these services with interactive manipulation of molecular sequences and structures, and we provide an example Python program to demonstrate how easily Opal-based web services can be accessed from within an application. Web server availability: http://webservices.rbvi.ucsf.edu/opal2/dashboard?command=serviceList. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

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

    International Nuclear Information System (INIS)

    Korngold, R.; Doherty, P.C.

    1982-01-01

    The virus-immune responder characteristics of thymocytes, spleen and lymph node (LN) cells from (P 1 x P 2 )F 1 →P 1 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 P 1 . This pattern of H-2 restriction is also maintained for spleen and LN cells from the [(H-2sup(kxd)F 1 →H-2sup(k)] and [(H-2sup(kxb)F 1 →H-2sup(k)] combinations but there is random emergence of reactivity to H-2sup(k)+virus for peripheral lymphoid cells from [(H-2sup(kxb)F 1 →H-2sup(b)] chimeras. Treatment of established [(P 1 xP 2 )]F 1 →P 1 ] 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.)

  16. A Universal Aptamer Chimera for the Delivery of Functional microRNA-126.

    Science.gov (United States)

    Rohde, Jan-H; Weigand, Julia E; Suess, Beatrix; Dimmeler, Stefanie

    2015-06-01

    microRNAs (miRs) regulate vascular diseases such as atherosclerosis and cancer. miR-126 is important for endothelial cell signaling and promotes angiogenesis, protects against atherosclerosis, and reduces breast cancer cell growth and metastasis. The overexpression of miR-126, therefore, may be an attractive therapeutic strategy for the treatment of cardiovascular disease or cancer. Here we report a novel strategy to deliver miR-126 to endothelial and breast cancer cells. We tested three different strategies to deliver miR-126 by linking the miR to an aptamer for the ubiquitously expressed transferrin receptor (transferrin receptor aptamer, TRA). Linking the precursor of miR-126 (pre-miR-126) to the TRA by annealing of a complementary stick led to efficient uptake and processing of miR-126, resulting in the delivery of 1.6×10(6)±0.3×10(6) copies miR-126-3p per ng RNA in human endothelial cells and 7.4×10(5)±2×10(5) copies miR-126-3p per ng in MCF7 breast cancer cells. The functionality of the active TRA-miR-126 chimera was further demonstrated by showing that the chimera represses the known miR-126 target VCAM-1 and improved endothelial cell sprouting in a spheroid assay. Moreover, the TRA-miR-126 chimera reduced proliferation and paracrine endothelial cell recruitment of breast cancer cells to a similar extent as miR-126-3p mimics introduced by conventional liposome-based transfection. Together, this data demonstrates that pre-miR-126 can be delivered by a non-specific aptamer to exert biological functions in two different cell models. The use of the TRA-miR-126 chimera or the combination of the delivery strategy with other endothelial or tumor specific aptamers may provide an interesting therapeutic option to treat vascular disease or cancers.

  17. Endothelial-regenerating cells: an expanding universe.

    Science.gov (United States)

    Steinmetz, Martin; Nickenig, Georg; Werner, Nikos

    2010-03-01

    Atherosclerosis is the most common cause for cardiovascular diseases and is based on endothelial dysfunction. A growing body of evidence suggests the contribution of bone marrow-derived endothelial progenitor cells, monocytic cells, and mature endothelial cells to vessel formation and endothelial rejuvenation. To this day, various subsets of these endothelial-regenerating cells have been identified according to cellular origin, phenotype, and properties in vivo and in vitro. However, the definition and biology, especially of endothelial progenitor cells, is complex and under heavy debate. In this review, we focus on current definitions of endothelial progenitor cells, highlight the clinical relevance of endothelial-regenerating cells, and provide new insights into cell-cell interactions involved in endothelial cell rejuvenation.

  18. Chimera states in mechanical oscillator networks.

    Science.gov (United States)

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

    2013-06-25

    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 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 of whether chimeras are indeed characteristic of 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 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-organization observed 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.

  19. Functional clonal deletion versus suppressor cell-induced transplantation tolerance in chimeras prepared with a short course of total-lymphoid irradiation

    International Nuclear Information System (INIS)

    Slavin, S.; Morecki, S.; Weigensberg, M.; Bar, S.; Weiss, L.

    1986-01-01

    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

  20. Chimera states: Effects of different coupling topologies

    Science.gov (United States)

    Bera, Bidesh K.; Majhi, Soumen; Ghosh, Dibakar; Perc, Matjaž

    2017-04-01

    Collective behavior among coupled dynamical units can emerge in various forms as a result of different coupling topologies as well as different types of coupling functions. Chimera states have recently received ample attention as a fascinating manifestation of collective behavior, in particular describing a symmetry breaking spatiotemporal pattern where synchronized and desynchronized states coexist in a network of coupled oscillators. In this perspective, we review the emergence of different chimera states, focusing on the effects of different coupling topologies that describe the interaction network connecting the oscillators. We cover chimera states that emerge in local, nonlocal and global coupling topologies, as well as in modular, temporal and multilayer networks. We also provide an outline of challenges and directions for future research.

  1. Construction of an Aptamer-SiRNA Chimera-Modified Tissue-Engineered Blood Vessel for Cell-Type-Specific Capture and Delivery.

    Science.gov (United States)

    Chen, Wen; Zeng, Wen; Sun, Jiansen; Yang, Mingcan; Li, Li; Zhou, Jingting; Wu, Yangxiao; Sun, Jun; Liu, Ge; Tang, Rui; Tan, Ju; Zhu, Chuhong

    2015-06-23

    The application of tissue-engineered blood vessels (TEBVs) is the main developmental direction of vascular replacement therapy. Due to few and/or dysfunctional endothelial progenitor cells (EPCs), it is difficult to successfully construct EPC capture TEBVs in diabetes. RNA has a potential application in cell protection and diabetes treatment, but poor specificity and low efficiency of RNA transfection in vivo limit the application of RNA. On the basis of an acellular vascular matrix, we propose an aptamer-siRNA chimera-modified TEBV that can maintain a satisfactory patency in diabetes. This TEBV consists of two parts, CD133-adenosine kinase (ADK) chimeras and a TEBV scaffold. Our results showed that CD133-ADK chimeras could selectively capture the CD133-positive cells in vivo, and then captured cells can internalize the bound chimeras to achieve RNA self-transfection. Subsequently, CD133-ADK chimeras were cut into ADK siRNA by a dicer, resulting in depletion of ADK. An ADK-deficient cell may act as a bioreactor that sustainably releases adenosine. To reduce nonspecific RNA transfection, we increased the proportion of HAuCl4 during the material preparation, through which the transfection capacity of polyethylenimine (PEI)/polyethylene glycol (PEG)-capped gold nanoparticles (PEI/PEG-AuNPs) was significantly decreased and the ability of TEBV to resist tensile and liquid shear stress was greatly enhanced. PEG and 2'-O-methyl modification was used to enhance the in vivo stability of RNA chimeras. At day 30 postgrafting, the patency rate of CD133-ADK chimera-modified TEBVs reached 90% in diabetic rats and good endothelialization was observed.

  2. α-Peptide/ß-Peptoid Chimeras

    DEFF Research Database (Denmark)

    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...

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

    DEFF Research Database (Denmark)

    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 a reversal...

  4. Bone marrow-derived versus parenchymal sources of inducible nitric oxide synthase in experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Zehntner, Simone P; Bourbonniere, Lyne; Hassan-Zahraee, Mina

    2004-01-01

    . These discrepancies may reflect balance between immunoregulatory and neurocytopathologic roles for NO. We investigated selective effects of bone marrow-derived versus CNS parenchymal sources of iNOS in EAE in chimeric mice. Chimeras that selectively expressed or ablated iNOS in leukocytes both showed significant...

  5. Chimera states in Gaussian coupled map lattices

    Science.gov (United States)

    Li, Xiao-Wen; Bi, Ran; Sun, Yue-Xiang; Zhang, Shuo; Song, Qian-Qian

    2018-04-01

    We study chimera states in one-dimensional and two-dimensional Gaussian coupled map lattices through simulations and experiments. Similar to the case of global coupling oscillators, individual lattices can be regarded as being controlled by a common mean field. A space-dependent order parameter is derived from a self-consistency condition in order to represent the collective state.

  6. Basins of Attraction for Chimera States

    DEFF Research Database (Denmark)

    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...

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

    International Nuclear Information System (INIS)

    Beschorner, W.E.; Tutschka, P.J.; Santos, G.W.

    1983-01-01

    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

  8. Graft-versus-host disease and sialodacryoadenitis viral infection in bone marrow transplanted rats

    International Nuclear Information System (INIS)

    Rossie, K.M.; Sheridan, J.F.; Barthold, S.W.; Tutschka, P.J.

    1988-01-01

    The effect of a localized viral infection on the occurrence of graft-vs.-host disease (GVHD) was examined in allogeneic rat bone marrow chimeras (ACI/LEW). Animals without clinical evidence of GVHD, 62 days after bone marrow transplant, were infected in salivary and lacrimal glands with sialodacryoadenitis virus (SDAV), and sacrificed 8-25 days postinfection. Using established histologic criteria, GVHD was found more frequently in salivary and lacrimal glands of SDAV-infected chimeras than uninfected chimeras. Skin and oral mucosa, tissues not infected by the virus, showed no differences in occurrence of GVHD, suggesting that the viral infection induced only local and not systemic GVHD. GVHD and SDAV infection, which are histologically similar, were differentiated by examining tissues for SDAV antigen using immunoperoxidase technique. Histologic changes were present for at least 1 week longer than viral antigen, suggesting they represented GVHD rather than viral infection. GVHD and SDAV infection were also differentiated by looking for a histologic feature characteristic of GVHD and not found in SDAV infection (periductal lymphocytic infiltrate). This was found in SDAV-infected chimeras more frequently than uninfected chimeras, suggesting that the viral infection somehow induced GVHD. Results showed a localized increase in the occurrence of GVHD subsequent to localized viral infection

  9. Early dominance of irradiated host cells in the responder profiles of thymocytes from P → F1 radiation chimeras

    International Nuclear Information System (INIS)

    Korngold, R.; Bennink, J.R.; Doherty, P.C.

    1981-01-01

    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)F 1 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

  10. Chimera states in nonlocally coupled phase oscillators with biharmonic interaction

    Science.gov (United States)

    Cheng, Hongyan; Dai, Qionglin; Wu, Nianping; Feng, Yuee; Li, Haihong; Yang, Junzhong

    2018-03-01

    Chimera states, which consist of coexisting domains of coherent and incoherent parts, have been observed in a variety of systems. Most of previous works on chimera states have taken into account specific form of interaction between oscillators, for example, sinusoidal coupling or diffusive coupling. Here, we investigate chimera dynamics in nonlocally coupled phase oscillators with biharmonic interaction. We find novel chimera states with features such as that oscillators in the same coherent cluster may split into two groups with a phase difference around π/2 and that oscillators in adjacent coherent clusters may have a phase difference close to π/2. The different impacts of the coupling ranges in the first and the second harmonic interactions on chimera dynamics are investigated based on the synchronous dynamics in globally coupled phase oscillators. Our study suggests a new direction in the field of chimera dynamics.

  11. The chimera state in colloidal phase oscillators with hydrodynamic interaction

    Science.gov (United States)

    Hamilton, Evelyn; Bruot, Nicolas; Cicuta, Pietro

    2017-12-01

    The chimera state is the incongruous situation where coherent and incoherent populations coexist in sets of identical oscillators. Using driven non-linear oscillators interacting purely through hydrodynamic forces at low Reynolds number, previously studied as a simple model of motile cilia supporting waves, we find concurrent incoherent and synchronised subsets in small arrays. The chimeras seen in simulation display a "breathing" aspect, reminiscent of uniformly interacting phase oscillators. In contrast to other systems where chimera has been observed, this system has a well-defined interaction metric, and we know that the emergent dynamics inherit the symmetry of the underlying Oseen tensor eigenmodes. The chimera state can thus be connected to a superposition of eigenstates, whilst considering the mean interaction strength within and across subsystems allows us to make a connection to more generic (and abstract) chimeras in populations of Kuramoto phase oscillators. From this work, we expect the chimera state to emerge in experimental observations of oscillators coupled through hydrodynamic forces.

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

    International Nuclear Information System (INIS)

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

    2014-01-01

    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)

  13. Persistent chimera states in nonlocally coupled phase oscillators

    OpenAIRE

    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 Rapid Communication, we numerically study chimera states by using the coupling function different from the previous studies and obtain the result that...

  14. Preliminary results of Digital Pulse Shape Acquisition from Chimera

    Energy Technology Data Exchange (ETDEWEB)

    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)

  15. Breathing chimera in a system of phase oscillators

    Science.gov (United States)

    Bolotov, M. I.; Smirnov, L. A.; Osipov, G. V.; Pikovsky, A. S.

    2017-09-01

    Chimera states consisting of synchronous and asynchronous domains in a medium of nonlinearly coupled phase oscillators have been considered. Stationary inhomogeneous solutions of the Ott-Antonsen equation for a complex order parameter that correspond to fundamental chimeras have been constructed. The direct numerical simulation has shown that these structures under certain conditions are transformed to oscillatory (breathing) chimera regimes because of the development of instability.

  16. Nonspecific suppressor elements in murine allogeneic radiation chimeras

    International Nuclear Information System (INIS)

    Urso, P.; Gengozian, N.

    1979-01-01

    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

  17. Preliminary results of Digital Pulse Shape Acquisition from Chimera

    International Nuclear Information System (INIS)

    Alderighi, D.M.; Sechi, G.; Anzalone, A.; Cavallaro, S.; Giustolisi, F.; Laguidara, E.; Lanzalone, G.; Porto, F.; Bassini, R.; Boiano, C.; Guazzoni, P.; Russo, S.; Sassi, M.; Zetta, L.; Cardella, G.; Defilippo, S.E.; Lanzano, G.; Paganod, A.; Papa, M.; Pirrone, S.; Politi, G.; Geraci, E.

    2003-01-01

    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)

  18. Chimera States in Mechanical Oscillator Networks

    OpenAIRE

    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 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...

  19. Computing Flows Using Chimera and Unstructured Grids

    Science.gov (United States)

    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.

  20. A New Approximate Chimera Donor Cell Search Algorithm

    Science.gov (United States)

    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.

  1. Chimera states in networks of logistic maps with hierarchical connectivities

    Science.gov (United States)

    zur Bonsen, Alexander; Omelchenko, Iryna; Zakharova, Anna; Schöll, Eckehard

    2018-04-01

    Chimera states are complex spatiotemporal patterns consisting of coexisting domains of coherence and incoherence. We study networks of nonlocally coupled logistic maps and analyze systematically how the dilution of the network links influences the appearance of chimera patterns. The network connectivities are constructed using an iterative Cantor algorithm to generate fractal (hierarchical) connectivities. Increasing the hierarchical level of iteration, we compare the resulting spatiotemporal patterns. We demonstrate that a high clustering coefficient and symmetry of the base pattern promotes chimera states, and asymmetric connectivities result in complex nested chimera patterns.

  2. Time-delayed feedback control of coherence resonance chimeras

    Science.gov (United States)

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

    2017-11-01

    Using the model of a FitzHugh-Nagumo system in the excitable regime, we investigate the influence of time-delayed feedback on noise-induced chimera states in a network with nonlocal coupling, i.e., coherence resonance chimeras. It is shown that time-delayed feedback allows for the control of the range of parameter values where these chimera states occur. Moreover, for the feedback delay close to the intrinsic period of the system, we find a novel regime which we call period-two coherence resonance chimera.

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

    International Nuclear Information System (INIS)

    Nisbet-Brown, E.; Diener, E.

    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

  4. Chimeric Mouse model to track the migration of bone marrow derived cells in glioblastoma following anti-angiogenic treatments.

    Science.gov (United States)

    Achyut, B R; Shankar, Adarsh; Iskander, A S M; Ara, Roxan; Knight, Robert A; Scicli, Alfonso G; Arbab, Ali S

    2016-01-01

    Bone marrow derived cells (BMDCs) have been shown to contribute in the tumor development. In vivo animal models to investigate the role of BMDCs in tumor development are poorly explored. We established a novel chimeric mouse model using as low as 5 × 10(6) GFP+ BM cells in athymic nude mice, which resulted in >70% engraftment within 14 d. In addition, chimera was established in NOD-SCID mice, which displayed >70% with in 28 d. Since anti-angiogenic therapies (AAT) were used as an adjuvant against VEGF-VEGFR pathway to normalize blood vessels in glioblastoma (GBM), which resulted into marked hypoxia and recruited BMDCs to the tumor microenvironment (TME). We exploited chimeric mice in athymic nude background to develop orthotopic U251 tumor and tested receptor tyrosine kinase inhibitors and CXCR4 antagonist against GBM. We were able to track GFP+ BMDCs in the tumor brain using highly sensitive multispectral optical imaging instrument. Increased tumor growth associated with the infiltration of GFP+ BMDCs acquiring suppressive myeloid and endothelial phenotypes was seen in TME following treatments. Immunofluorescence study showed GFP+ cells accumulated at the site of VEGF, SDF1 and PDGF expression, and at the periphery of the tumors following treatments. In conclusion, we developed a preclinical chimeric model of GBM and phenotypes of tumor infiltrated BMDCs were investigated in context of AATs. Chimeric mouse model could be used to study detailed cellular and molecular mechanisms of interaction of BMDCs and TME in cancer.

  5. Chimera states in a population of identical oscillators under planar ...

    Indian Academy of Sciences (India)

    finding, observed in both a collection of van der Pol oscillators and chaotic Rössler oscillators, fur- ther simplifies the existence criterion for chimeras, thereby broadens the range of their applicability to real-world situations. Keywords. Synchronization; chimera; Rössler system; van der Pol oscillator. PACS Nos 05.45.

  6. Assessing reprogramming by chimera formation and tetraploid complementation.

    Science.gov (United States)

    Li, Xin; Xia, Bao-long; Li, Wei; Zhou, Qi

    2015-01-01

    Pluripotent stem cells can be evaluated by pluripotent markers expression, embryoid body aggregation, teratoma formation, chimera contribution and even more, tetraploid complementation. Whether iPS cells in general are functionally equivalent to normal ESCs is difficult to establish. Here, we present the detailed procedure for chimera formation and tetraploid complementation, the most stringent criterion, to assessing pluripotency.

  7. Chimera patterns in the Kuramoto–Battogtokh model

    International Nuclear Information System (INIS)

    Smirnov, Lev; Osipov, Grigory; Pikovsky, Arkady

    2017-01-01

    Kuramoto and Battogtokh (2002 Nonlinear Phenom. Complex Syst . 5 380) discovered chimera states represented by stable coexisting synchrony and asynchrony domains in a lattice of coupled oscillators. After a reformulation in terms of a local order parameter, the problem can be reduced to partial differential equations. We find uniformly rotating, spatially periodic chimera patterns as solutions of a reversible ordinary differential equation, and demonstrate a plethora of such states. In the limit of neutral coupling they reduce to analytical solutions in the form of one- and two-point chimera patterns as well as localized chimera solitons. Patterns at weakly attracting coupling are characterized by virtue of a perturbative approach. Stability analysis reveals that only the simplest chimeras with one synchronous region are stable. (letter)

  8. Implementing real-time robotic systems using CHIMERA II

    Science.gov (United States)

    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.

  9. Chimera patterns in the Kuramoto-Battogtokh model

    Science.gov (United States)

    Smirnov, Lev; Osipov, Grigory; Pikovsky, Arkady

    2017-02-01

    Kuramoto and Battogtokh (2002 Nonlinear Phenom. Complex Syst. 5 380) discovered chimera states represented by stable coexisting synchrony and asynchrony domains in a lattice of coupled oscillators. After a reformulation in terms of a local order parameter, the problem can be reduced to partial differential equations. We find uniformly rotating, spatially periodic chimera patterns as solutions of a reversible ordinary differential equation, and demonstrate a plethora of such states. In the limit of neutral coupling they reduce to analytical solutions in the form of one- and two-point chimera patterns as well as localized chimera solitons. Patterns at weakly attracting coupling are characterized by virtue of a perturbative approach. Stability analysis reveals that only the simplest chimeras with one synchronous region are stable.

  10. Metaphysical and ethical perspectives on creating animal-human chimeras.

    Science.gov (United States)

    Eberl, Jason T; Ballard, Rebecca A

    2009-10-01

    This paper addresses several questions related to the nature, production, and use of animal-human (a-h) chimeras. At the heart of the issue is whether certain types of a-h chimeras should be brought into existence, and, if they are, how we should treat such creatures. In our current research environment, we recognize a dichotomy between research involving nonhuman animal subjects and research involving human subjects, and the classification of a research protocol into one of these categories will trigger different ethical standards as to the moral permissibility of the research in question. Are a-h chimeras entitled to the more restrictive and protective ethical standards applied to human research subjects? We elucidate an Aristotelian-Thomistic metaphysical framework in which to argue how such chimeras ought to be defined ontologically. We then examine when the creation of, and experimentation upon, certain types of a-h chimeras may be morally permissible.

  11. Leukemia prevention and long-term survival of AKR mice transplanted with MHC-matched or MHC-mismatched bone marrow

    International Nuclear Information System (INIS)

    Longley, R.E.; Good, R.A.

    1986-01-01

    The current studies were designed to evaluate the effectiveness of marrow transplantation within and outside the major histocompatibility complex (MHC) on the long-term survival and occurrence of spontaneous leukemia in AKR mice. AKR mice, which were lethally irradiated and received MHC-matched marrow from CBA/J mice (CBA----AKR), never developed leukemia and were alive and remained healthy for up to 280 days post-transplant. These long-term surviving chimeras possessed substantial immune vigor when both cell-mediated and humoral responses were tested. Lethally irradiated AKR mice, which had received MHC-mismatched marrow (anti-Thy-1.2 treated or nontreated) from C57BL/6J mice (B6----AKR), never developed leukemia and survived up to 170 days post-transplant. However, both groups of these chimeras began dying 180 to 270 days post-transplant due to a disease process which could not be readily identified. Histological analysis of B6----AKR chimeras revealed severe lymphoid cell depletion in thymus and spleen; however, none of these chimeras exhibited classical features of acute graft versus host disease. Concanavalin A mitogenesis, primary antibody responses to sheep red blood cells and the production of interleukin 2 (IL-2) were suppressed in B6----AKR chimeras. IL-2 treatment of B6----AKR chimeras was shown to partially correct these deficiencies without stimulating mixed lymphocyte responsiveness to donor or host lymphocytes. These studies indicate that the use of MHC-mismatched marrow for the prevention of spontaneous AKR leukemia may rely on augmentative IL-2 therapy for complete immune reconstitution of leukemia-free chimeras

  12. Solvable model of spiral wave chimeras.

    Science.gov (United States)

    Martens, Erik A; Laing, Carlo R; Strogatz, Steven H

    2010-01-29

    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.

  13. A 3-D chimera grid embedding technique

    Science.gov (United States)

    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.

  14. Solvable Model of Spiral Wave Chimeras

    DEFF Research Database (Denmark)

    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....

  15. Can bone marrow differentiate into renal cells?

    Science.gov (United States)

    Imai, Enyu; Ito, Takahito

    2002-10-01

    A considerable plasticity of adult stem cells has been confirmed in a wide variety of tissues. In particular, the pluripotency of bone marrow-derived stem cells may influence the regeneration of injured tissues and may provide novel avenues in regenerative medicine. Bone marrow contains at least hematopoietic and mesenchymal stem cells, and both can differentiate into a wide range of differentiated cells. Side population (SP) cells, which are originally defined in bone marrow cells by high efflux of DNA-binding dye, seem to be a new class of multipotent stem cells. Irrespective of the approach used to obtain stem cells, the fates of marrow-derived cells following bone marrow transplantation can be traced by labeling donor cells with green fluorescence protein or by identifying donor Y chromosome in female recipients. So far, bone marrow-derived cells have been reported to differentiate into renal cells, including mesangial cells, endothelial cells, podocytes, and tubular cells in the kidney, although controversy exists. Further studies are required to address this issue. Cell therapy will be promising when we learn to control stem cells such as bone marrow-derived stem cells, embryonic stem cells, and resident stem cells in the kidney. Identification of factors that support stem cells or promote their differentiation should provide a relevant step towards cell therapy.

  16. 77 FR 65602 - Chimera Energy Corporation; Order of Suspension of Trading

    Science.gov (United States)

    2012-10-29

    ... SECURITIES AND EXCHANGE COMMISSION [File No. 500-1] Chimera Energy Corporation; Order of... lack of current and accurate information concerning the securities of Chimera Energy Corporation (``Chimera'') because of questions regarding the accuracy of statements by Chimera in press releases to...

  17. Bone marrow-derived thymic antigen-presenting cells determine self-recognition of Ia-restricted T lymphocytes

    International Nuclear Information System (INIS)

    Longo, D.L.; Kruisbeek, A.M.; Davis, M.L.; Matis, L.A.

    1985-01-01

    The authors previously have demonstrated that in radiation-induced bone marrow chimeras, T-cell self-Ia restriction specificity appeared to correlate with the phenotype of the bone marrow-derived antigen-presenting (or dendritic) cell in the thymus during T-cell development. However, these correlations were necessarily indirect because of the difficulty in assaying thymic function directly by adult thymus transplant, which has in the past been uniformly unsuccessful. They now report success in obtaining functional T cells from nude mice grafted with adult thymuses reduced in size by treatment of the thymus donor with anti-thymocyte globulin and cortisone. When (B10 Scn X B10.D2)F1 nude mice (I-Ab,d) are given parental B10.D2 (I-Ad) thymus grafts subcutaneously, their T cells are restricted to antigen recognition in association with I-Ad gene products but not I-Ab gene products. Furthermore, thymuses from (B10 X B10.D2)F1 (I-Ab,d)----B10 (I-Ab) chimeras transplanted 6 months or longer after radiation (a time at which antigen-presenting cell function is of donor bone marrow phenotype) into (B10 X B10.D2)F1 nude mice generate T cells restricted to antigen recognition in association with both I-Ad and I-Ab gene products. Thymuses from totally allogeneic bone marrow chimeras appear to generate T cells of bone marrow donor and thymic host restriction specificity. Thus, when thymus donors are radiation-induced bone marrow chimeras, the T-cell I-region restriction of the nude mice recipients is determined at least in part by the phenotype of the bone marrow-derived thymic antigen presenting cells or dendritic cells in the chimeric thymus

  18. Cellular basis of the immunohematologic defects observed in short-term semiallogeneic B6C3F1→C3H chimeras: evidence for host-versus-graft reaction initiated by radioresistant T cells

    International Nuclear Information System (INIS)

    Aizawa, S.; Sado, T.; Kamisaku, H.; Kubo, E.

    1980-01-01

    Lethally irradiated C3Hf mice reconstituted with a relatively low dose (2 x 10 6 ) of B6C3F 1 bone marrow cells (B6C3F 1 →C3Hf chimeras) frequently manifest immunohematologic deficiencies during the first month following injection of bone marrow cells. They show slow recovery of antibody-forming potential to sheep red blood cells (SRBC) as compared to that observed in syngeneic (C3Hf→C3Hf or B6C3F 1 →B6C3F 1 ) chimeras. They also show a deficiency of B-cell activity as assessed by antibody response to SRBC following further reconstitution with B6C3F 1 -derived thymus cells 1 week after injection of bone marrow cells. A significant fraction of B6C3F 1 →C3Hf chimeras was shown to manifest a sudden loss of cellularity of spleens during the second week following injection of bone marrow cells even though cellularity was restored to the normal level within 1 week. The splenic mononuclear cells recovered from such chimeras almost invariably showed strong cytotoxicity against target cells expressing donor-type specific H-2 antigens (H-2/sup b/) when assesed by 51 Cr-release assay in vitro. The effector cells responsible for the observed anti-donor specific cytotoxicity were shown to be residual host-derived T cells. These results indicate strongly that residual host T cells could develop anti-donor specific cytotoxicity even after exposure to a supralethal dose (1050 R) of radiation and that the immunohematologic disturbances observed in shortterm F 1 to parent bone marrow chimeras (B6C3F 1 →C3Hf) were due to host-versus-graft reaction (HVGR) initiated by residual host T cells. The implication of these findings on the radiobiological nature of the residual T cells and the persistence of potentially anti-donor reactive T-cell clones in long-surviving allogeneic bone marrow chimeras was discussed

  19. Connecting the Kuramoto Model and the Chimera State

    Science.gov (United States)

    Kotwal, Tejas; Jiang, Xin; Abrams, Daniel M.

    2017-12-01

    Since its discovery in 2002, the chimera state has frequently been described as a counterintuitive, puzzling phenomenon. The Kuramoto model, in contrast, has become a celebrated paradigm useful for understanding a range of phenomena related to phase transitions, synchronization, and network effects. Here we show that the chimera state can be understood as emerging naturally through a symmetry-breaking bifurcation from the Kuramoto model's partially synchronized state. Our analysis sheds light on recent observations of chimera states in laser arrays, chemical oscillators, and mechanical pendula.

  20. Signaling hierarchy regulating human endothelial cell development.

    Science.gov (United States)

    Kelly, Melissa A; Hirschi, Karen K

    2009-05-01

    Our present knowledge of the regulation of mammalian endothelial cell differentiation has been largely derived from studies of mouse embryonic development. However, unique mechanisms and hierarchy of signals that govern human endothelial cell development are unknown and, thus, explored in these studies. Using human embryonic stem cells as a model system, we were able to reproducibly and robustly generate differentiated endothelial cells via coculture on OP9 marrow stromal cells. We found that, in contrast to studies in the mouse, bFGF and VEGF had no specific effects on the initiation of human vasculogenesis. However, exogenous Ihh promoted endothelial cell differentiation, as evidenced by increased production of cells with cobblestone morphology that coexpress multiple endothelial-specific genes and proteins, form lumens, and exhibit DiI-AcLDL uptake. Inhibition of BMP signaling using Noggin or BMP4, specifically, using neutralizing antibodies suppressed endothelial cell formation; whereas, addition of rhBMP4 to cells treated with the hedgehog inhibitor cyclopamine rescued endothelial cell development. Our studies revealed that Ihh promoted human endothelial cell differentiation from pluripotent hES cells via BMP signaling, providing novel insights applicable to modulating human endothelial cell formation and vascular regeneration for human clinical therapies.

  1. Major Histocompatibilty Complex-Restricted Adaptive Immune Responses to CT26 Colon Cancer Cell Line in Mixed Allogeneic Chimera.

    Science.gov (United States)

    Lee, K W; Choi, B; Kim, Y M; Cho, C W; Park, H; Moon, J I; Choi, G-S; Park, J B; Kim, S J

    2017-06-01

    Although the induction of mixed allogeneic chimera shows promising clinical tolerance results in organ transplantation, its clinical relevance as an anti-cancer therapy is yet unknown. We introduced a mixed allogenic chimera setting with the use of a murine colon cancer cell line, CT26, by performing double bone marrow transplantation. We analyzed donor- and recipient-restricted anti-cancer T-cell responses, and phenotypes of subpopulations of T cells. The protocol involves challenging 1 × 10 5 cells of CT26 cells intra-hepatically on day 50 after bone marrow transplantation, and, by use of CT26 lysates and an H-2L d -restricted AH1 pentamer, flow cytometric analysis was performed to detect the generation of cancer-specific CD4 + and CD8 + T cells at various time points. We found that immunocompetence against tumors depends heavily on cancer-specific CD8 + T-cell responses in a major histocompatibility complex-restricted manner; the evidence was further supported by the increase of interferon-γ-secreting CD4 + T cells. Moreover, we demonstrated that during the effector immune response to CT26 cancer challenge, there was a presence of central memory cells (CD62L hi CCR7 + ) as well as effector memory cells (CD62L lo CCR7 - ). Moreover, mixed allogeneic chimeras (BALB/c to C56BL/6 or vice versa) showed similar or heightened immune responses to CT26 cells compared with that of wild-type mice. Our results suggest that the responses of primary immunocompetency and of pre-existing memory T cells against allogeneic cancer are sustained and preserved long-term in a mixed allogeneic chimeric environment. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Radiosensitivity and chimera formation in Hibiscus syriacus

    International Nuclear Information System (INIS)

    Kwon, S.H.; Won, J.L.

    1980-01-01

    Radiosensitivity of gamma-irradiated Hibiscus syriacus and chimera formation were investigated. The lethal dose-50 percent with respect to seeding and cuttings was 15kR and 2 approximately 3 kR respectively, chlorophyll mutation rate of seeds irradiated with 15 kR being about 13 percent. The degree of chimeric leaf mutants from the buds by radiation treatment depends on the bud position of the branch. Buds of the middle part of V 1 branch seemed to be more multi-cellular condition than the upper and low part when irradiation was made. It is assumed that at least two primordia of V 2 branch were already differentiated from the V 1 branch in Hibiscus syriacus plant. (Author)

  3. Chimeras and Mirages of the Golden Horde

    Directory of Open Access Journals (Sweden)

    V.A. Ivanov

    2014-01-01

    Full Text Available The article examines the problem of so-called “imperial culture” of the Golden Horde. The author analyzes the archaeological material regarding it as a component of “imperial culture”. The author evaluates the quality of the archaeological material as well as the breadth and intensity of its distribution among the population of the Golden Horde and the neighboring tribal areas, which the author considers a priori as consumers of this “imperial culture”. Based on this analysis, the author concludes that in general, the concept of “imperial culture” of the Golden Horde is a chimera. In turn, the expected powerful effect of “imperial culture” of the Golden Horde in the culture of neighboring peoples of the Urals and the Volga region is a mirage created by the imagination of researchers.

  4. Grid adaptation using chimera composite overlapping meshes

    Science.gov (United States)

    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.

  5. Grid adaption using Chimera composite overlapping meshes

    Science.gov (United States)

    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.

  6. Stable Chimeras and Independently Synchronizable Clusters

    Science.gov (United States)

    Cho, Young Sul; Nishikawa, Takashi; Motter, Adilson E.

    2017-08-01

    Cluster synchronization is a phenomenon in which a network self-organizes into a pattern of synchronized sets. It has been shown that diverse patterns of stable cluster synchronization can be captured by symmetries of the network. Here, we establish a theoretical basis to divide an arbitrary pattern of symmetry clusters into independently synchronizable cluster sets, in which the synchronization stability of the individual clusters in each set is decoupled from that in all the other sets. Using this framework, we suggest a new approach to find permanently stable chimera states by capturing two or more symmetry clusters—at least one stable and one unstable—that compose the entire fully symmetric network.

  7. Application of Chimera Composite Grid Scheme to Ship Appendages

    National Research Council Canada - National Science Library

    Lin, Cheng-Wen

    1995-01-01

    .... The chimera scheme of grid generation uses a system of relatively simple grids. The grids each define a particular component of the overall geometry, making the initial grid generation much simpler...

  8. Is repulsion good for the health of chimeras?

    Science.gov (United States)

    Jalan, Sarika; Ghosh, Saptarshi; Patra, Bibhabasu

    2017-10-01

    Yes! Very much so. A chimera state refers to the coexistence of a coherent-incoherent dynamical evolution of identically coupled oscillators. We investigate the impact of multiplexing of a layer having repulsively coupled oscillators on the occurrence of chimeras in the layer having attractively coupled identical oscillators. We report that there exists an enhancement in the appearance of the chimera state in one layer of the multiplex network in the presence of repulsive coupling in the other layer. Furthermore, we show that a small amount of inhibition or repulsive coupling in one layer is sufficient to yield the chimera state in another layer by destroying its synchronized behavior. These results can be used to obtain insight into dynamical behaviors of those systems where both attractive and repulsive couplings exist among their constituents.

  9. Navier-Stokes Computations of Sabot Discard Using Chimera Scheme

    National Research Council Canada - National Science Library

    Ferry, E

    1997-01-01

    .... Numerical flow field computations have been made for various orientations and locations of sabots using an unsteady, zonal Navier-Stokes code and the Chimera composite grid discretization technique at M = 4.0 and alpha = 0...

  10. Chimera States in Two Populations with Heterogeneous Phase-lag

    DEFF Research Database (Denmark)

    Martens, Erik Andreas; Bick, Christian; Panaggio, Mark

    2016-01-01

    The simplest network of coupled phase-oscillators exhibiting chimera states is given by two populations with disparate intra- and inter-population coupling strengths. We explore the effects of heterogeneous coupling phase-lags between the two populations. Such heterogeneity arises naturally......-uniform synchronization, including in-phase and anti-phase synchrony, full incoherence (splay state), chimera states with phase separation of 0 or π between populations, and states where both populations remain desynchronized. These desynchronized states exhibit stable, oscillatory, and even chaotic dynamics. Moreover......, we identify the bifurcations through which chimera and desynchronized states emerge. Stable chimera states and desynchronized solutions, which do not arise for homogeneous phase-lag parameters, emerge as a result of competition between synchronized in-phase, anti-phase equilibria, and fully...

  11. Optimal design of tweezer control for chimera states

    Science.gov (United States)

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

    2018-01-01

    Chimera states are complex spatio-temporal patterns which consist of coexisting domains of spatially coherent and incoherent dynamics in systems of coupled oscillators. In small networks, chimera states usually exhibit short lifetimes and erratic drifting of the spatial position of the incoherent domain. A tweezer feedback control scheme can stabilize and fix the position of chimera states. We analyze the action of the tweezer control in small nonlocally coupled networks of Van der Pol and FitzHugh-Nagumo oscillators, and determine the ranges of optimal control parameters. We demonstrate that the tweezer control scheme allows for stabilization of chimera states with different shapes, and can be used as an instrument for controlling the coherent domains size, as well as the maximum average frequency difference of the oscillators.

  12. Thy-1+ dendritic cells in murine epidermis are bone marrow-derived

    International Nuclear Information System (INIS)

    Breathnach, S.M.; Katz, S.I.

    1984-01-01

    Thy-1+, Ly-5+ dendritic cells have recently been described as a resident cell population in murine epidermis, but their ontogeny and function are unknown. The origin and turnover of epidermal Thy-1+ cells utilizing chimeric mice were investigated. Lethally x-irradiated AKR/J (Thy-1.1+) and AKR/Cum (Thy-1.2+) mice were reconstituted with allogeneic bone marrow cells with or without thymocytes from congenic AKR/Cum or AKR/J mice, respectively. The density of residual indigenous Thy-1.1+ cells in AKR/J chimeras and Thy-1.2+ cells in AKR/Cum chimeras was substantially reduced following x-irradiation, as determined by immunofluorescence staining of epidermal sheets. Epidermal repopulation by allogeneic Thy-1+ dendritic epidermal cells was first observed at 5 weeks in AKR/J chimeras and at 7 weeks in AKR/Cum chimeras and progressed slowly. Repopulation was not enhanced by increasing the number of allogeneic bone marrow cells injected from 2 X 10(7) to 10(8) cells or by the addition of 8 X 10(7) allogeneic thymocytes to the donor inoculate. Epidermal repopulation by allogeneic Thy-1.2+ cells was not seen in AKR/J mice reconstituted with syngeneic bone marrow cells and allogeneic Thy-1.2+ AKR/Cum thymocytes. Taken together, these results indicate that Thy-1+ dendritic epidermal cells are derived from the bone marrow and suggest that they are not related to conventional peripheral T-lymphocytes

  13. Chimera states in bipartite networks of FitzHugh-Nagumo oscillators

    Science.gov (United States)

    Wu, Zhi-Min; Cheng, Hong-Yan; Feng, Yuee; Li, Hai-Hong; Dai, Qiong-Lin; Yang, Jun-Zhong

    2018-04-01

    Chimera states consisting of spatially coherent and incoherent domains have been observed in different topologies such as rings, spheres, and complex networks. In this paper, we investigate bipartite networks of nonlocally coupled FitzHugh-Nagumo (FHN) oscillators in which the units are allocated evenly to two layers, and FHN units interact with each other only when they are in different layers. We report the existence of chimera states in bipartite networks. Owing to the interplay between chimera states in the two layers, many types of chimera states such as in-phase chimera states, antiphase chimera states, and out-of-phase chimera states are classified. Stability diagrams of several typical chimera states in the coupling strength-coupling radius plane, which show strong multistability of chimera states, are explored.

  14. Plant chimeras: The good, the bad, and the 'Bizzaria'.

    Science.gov (United States)

    Frank, Margaret H; Chitwood, Daniel H

    2016-11-01

    Chimeras - organisms that are composed of cells of more than one genotype - captured the human imagination long before they were formally described and used in the laboratory. These organisms owe their namesake to a fire-breathing monster from Greek mythology that has the head of a lion, the body of a goat, and the tail of a serpent. The first description of a non-fictional chimera dates back to the middle of the seventeenth century when the Florentine gardener Pietro Nati discovered an adventitious shoot growing from the graft junction between sour orange (Citrus aurantium) and citron (Citrus medica). This perplexing chimera that grows with sectors phenotypically resembling each of the citrus progenitors inspired discussion and wonder from the scientific community and was fittingly named the 'Bizzaria'. Initially, the 'Bizzaria' was believed to be an asexual hybrid that formed from a cellular fusion between the grafted parents; however, in-depth cellular analyses carried out centuries later demonstrated that the 'Bizzaria', along with other chimeras, owe their unique sectored appearance to a conglomeration of cells from the two donors. Since this pivotal discovery at the turn of the twentieth century, chimeras have served both as tools and as unique biological phenomena that have contributed to our understanding of plant development at the cellular, tissue, and organismal level. Rapid advancements in genome sequencing technologies have enabled the establishment of new model species with novel morphological and developmental features that enable the generation of chimeric organisms. In this review, we show that genetic mosaic and chimera studies provide a technologically simple way to delve into the organismal, genetic, and genomic inner workings underlying the development of diverse model organisms. Moreover, we discuss the unique opportunity that chimeras present to explore universal principles governing intercellular communication and the coordination of

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

    Directory of Open Access Journals (Sweden)

    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

  16. Genetic resistance in experimental autoimmune encephalomyelitis. I. Analysis of the mechanism of LeR resistance using radiation chimeras

    International Nuclear Information System (INIS)

    Pelfrey, C.M.; Waxman, F.J.; Whitacre, C.C.

    1989-01-01

    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

  17. Immune transfer studies in canine allogeneic marrow graft donor-recipient pairs

    International Nuclear Information System (INIS)

    Grosse-Wilde, H.; Krumbacher, K.; Schuening, F.D.; Doxiadis, I.; Mahmoud, H.K.; Emde, C.; Schmidt-Weinmar, A.; Schaefer, U.W.

    1986-01-01

    Transfer of immunity occurring with bone marrow grafting was studied using the dog as a preclinical model. Allogeneic bone marrow transplantation (BMT) was performed between DLA-identical beagle litter-mates. The donors were immunized with tetanus toxoid (TT) or sheep red blood cells (SRBC), and their humoral response was monitored by hemagglutination. The recipients of bone marrow from TT-immunized donors showed a marked increase of antibody titer one week posttransplantation, while in the recipients of marrow from SRBC immunized donors the antibody titers were considerably lower. Within the following 60 days the antibody titers in both groups diminished gradually to pregrafting levels. Control experiments in which cell-free plasma from donors immunized with TT and SRBC respectively was transfused indicated that the initial rise of specific antibody titers after marrow grafting is likely to be due to a passive transfer of humoral immunity. A single challenge of these marrow graft recipients with the respective antigen 15-18 weeks posttransplantation led to a secondary type of humoral immune response. It could be demonstrated that transfer of memory against TT or SRBC was independent from the actual antibody titer and the time of vaccination of the donor. One dog was immunized with TT after serving as marrow donor. When the donor had shown an antibody response, a peripheral blood leukocytes (PBL) transfusion was given to his chimera. Subsequent challenge of the latter resulted in a secondary type of specific antibody response. This indicates that specific cellular-bound immunological memory can be transferred after BMT from the donor to his allogeneic bone marrow chimera by transfusion of peripheral blood leukocytes. The data may be of importance in clinical BMT to protect patients during the phase of reduced immune reactivity by transfer of memory cells

  18. Double-well chimeras in 2D lattice of chaotic bistable elements

    Science.gov (United States)

    Shepelev, I. A.; Bukh, A. V.; Vadivasova, T. E.; Anishchenko, V. S.; Zakharova, A.

    2018-01-01

    We investigate spatio-temporal dynamics of a 2D ensemble of nonlocally coupled chaotic cubic maps in a bistability regime. In particular, we perform a detailed study on the transition ;coherence - incoherence; for varying coupling strength for a fixed interaction radius. For the 2D ensemble we show the appearance of amplitude and phase chimera states previously reported for 1D ensembles of nonlocally coupled chaotic systems. Moreover, we uncover a novel type of chimera state, double-well chimera, which occurs due to the interplay of the bistability of the local dynamics and the 2D ensemble structure. Additionally, we find double-well chimera behavior for steady states which we call double-well chimera death. A distinguishing feature of chimera patterns observed in the lattice is that they mainly combine clusters of different chimera types: phase, amplitude and double-well chimeras.

  19. Chimera states in coupled Kuramoto oscillators with inertia

    International Nuclear Information System (INIS)

    Olmi, Simona

    2015-01-01

    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

  20. Chimera states in coupled Kuramoto oscillators with inertia

    Energy Technology Data Exchange (ETDEWEB)

    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.

  1. Chimera states in coupled Kuramoto oscillators with inertia.

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Semenov, V. [Department of Physics, Saratov State University, Astrakhanskaya Str. 83, 410012 Saratov (Russian Federation); Zakharova, A.; Schöll, E. [Institut für Theoretische Physik, TU Berlin, Hardenbergstraße 36, 10623 Berlin (Germany); Maistrenko, Y. [Institute of Mathematics and Center for Medical and Biotechnical Research, NAS of Ukraine, Tereschenkivska Str. 3, 01601 Kyiv (Ukraine)

    2016-06-08

    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.

  3. Pulse shape method for the Chimera silicon detectors

    Energy Technology Data Exchange (ETDEWEB)

    Pagano, A.; Arena, N.; Cardella, G.; D' Andrea, M.; Filippo, E. de; Fichera, F.; Giudice, N.; Guardone, N.; Grimaldi, A.; Nicotra, D.; Papa, M.; Pirrone, S.; Politi, G.; Rapicavoli, C.; Rizza, G.; Russotto, P.; Sacca, G.; Urso, S.; Lanzano, G. [Catania Univ., INFN Catania and Dipartimento di Fisica e Astronomia (Italy); Alderighi, M.; Sechi, G. [INFN Milano and Istituto di Fisica Cosmica CNR, Milano (Italy); Amorini, F.; Anzalone, A.; Cali, C.; Campagna, V.; Cavallaro, S.; Di Stefano, A.; Giustolisi, F.; La Guidara, E.; Lanzalone, G.; Maiolino, C.; Porto, F.; Rizzo, F.; Salamone, S. [Catania Univ., INFN-LNS and Dipartimento di Fisica e Astronomia (Italy); Auditore, L.; Trifiro, A.; Trimarchi, M. [Messina Univ., INFN and Dipartimento di Fisica (Italy); Bassini, R.; Boiano, C.; Guazzoni, P.; Russo, S.; Sassi, M.; Zetta, L. [Milano Univ., INFN Milano and Dipartimento di Fisica (Italy); Blicharska, J.; Grzeszczuk, A. [Silesia Univ., Institute of Physics, Katowice (Poland); Chatterjee, M.B. [Saha Institute Of Nuclear Physics, Kolkata (India); Geraci, E.; Zipper, W. [Bologna Univ., INFN Bologna and Dipartimento di Fisica (Italy); Rosato, E.; Vigilante, M. [Napoli Univ., INFN and Dipartimento di Fisica (Italy); Schroder, W.U.; T-ke, J. [Rochester Univ., Dept. of Chemistry, Rochester, N.Y. (United States)

    2003-07-01

    Since January 2003, the 4{pi} CHIMERA (Charged Heavy Ions Mass and Energy Resolving Array) detector in its full configuration has successfully been operated at the 'Catania Laboratori Nazionali del Sud' (LNS) accelerator facility. The detector has been used with a variety of beams from the Superconducting Cyclotron in heavy-ion reaction studies at Fermi bombarding energies. Future experiments with a focus on isospin physics at Fermi energies, planned for both primary and less intense secondary particle beams, suggest the development of new and more versatile experimental particle identification methods. Recent achievements in implementing specific pulse shape particle identification methods for CHIMERA silicon detectors are reported. They suggest an upgrade of the present charge and mass identification capability of CHIMERA by a simple extension of the method. (authors)

  4. Chimera States in Continuous Media: Existence and Distinctness

    Science.gov (United States)

    Nicolaou, Zachary G.; Riecke, Hermann; Motter, Adilson E.

    2017-12-01

    The defining property of chimera states is the coexistence of coherent and incoherent domains in systems that are structurally and spatially homogeneous. The recent realization that such states might be common in oscillator networks raises the question of whether an analogous phenomenon can occur in continuous media. Here, we show that chimera states can exist in continuous systems even when the coupling is strictly local, as in many fluid and pattern forming media. Using the complex Ginzburg-Landau equation as a model system, we characterize chimera states consisting of a coherent domain of a frozen spiral structure and an incoherent domain of amplitude turbulence. We show that in this case, in contrast with discrete network systems, fluctuations in the local coupling field play a crucial role in limiting the coherent regions. We suggest these findings shed light on new possible forms of coexisting order and disorder in fluid systems.

  5. Mechanism of chimera formation during the Multiple Displacement Amplification reaction

    Directory of Open Access Journals (Sweden)

    Stockwell Timothy B

    2007-04-01

    Full Text Available Abstract Background Multiple Displacement Amplification (MDA is a method used for amplifying limiting DNA sources. The high molecular weight amplified DNA is ideal for DNA library construction. While this has enabled genomic sequencing from one or a few cells of unculturable microorganisms, the process is complicated by the tendency of MDA to generate chimeric DNA rearrangements in the amplified DNA. Determining the source of the DNA rearrangements would be an important step towards reducing or eliminating them. Results Here, we characterize the major types of chimeras formed by carrying out an MDA whole genome amplification from a single E. coli cell and sequencing by the 454 Life Sciences method. Analysis of 475 chimeras revealed the predominant reaction mechanisms that create the DNA rearrangements. The highly branched DNA synthesized in MDA can assume many alternative secondary structures. DNA strands extended on an initial template can be displaced becoming available to prime on a second template creating the chimeras. Evidence supports a model in which branch migration can displace 3'-ends freeing them to prime on the new templates. More than 85% of the resulting DNA rearrangements were inverted sequences with intervening deletions that the model predicts. Intramolecular rearrangements were favored, with displaced 3'-ends reannealing to single stranded 5'-strands contained within the same branched DNA molecule. In over 70% of the chimeric junctions, the 3' termini had initiated priming at complimentary sequences of 2–21 nucleotides (nts in the new templates. Conclusion Formation of chimeras is an important limitation to the MDA method, particularly for whole genome sequencing. Identification of the mechanism for chimera formation provides new insight into the MDA reaction and suggests methods to reduce chimeras. The 454 sequencing approach used here will provide a rapid method to assess the utility of reaction modifications.

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

    Science.gov (United States)

    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

  7. Chimera-like states in structured heterogeneous networks

    Science.gov (United States)

    Li, Bo; Saad, David

    2017-04-01

    Chimera-like states are manifested through the coexistence of synchronous and asynchronous dynamics and have been observed in various systems. To analyze the role of network topology in giving rise to chimera-like states, we study a heterogeneous network model comprising two groups of nodes, of high and low degrees of connectivity. The architecture facilitates the analysis of the system, which separates into a densely connected coherent group of nodes, perturbed by their sparsely connected drifting neighbors. It describes a synchronous behavior of the densely connected group and scaling properties of the induced perturbations.

  8. Strategies to reverse endothelial progenitor cell dysfunction in diabetes.

    Science.gov (United States)

    Petrelli, Alessandra; Di Fenza, Raffaele; Carvello, Michele; Gatti, Francesca; Secchi, Antonio; Fiorina, Paolo

    2012-01-01

    Bone-marrow-derived cells-mediated postnatal vasculogenesis has been reported as the main responsible for the regulation of vascular homeostasis in adults. Since their discovery, endothelial progenitor cells have been depicted as mediators of postnatal vasculogenesis for their peculiar phenotype (partially staminal and partially endothelial), their ability to differentiate in endothelial cell line and to be incorporated into the vessels wall during ischemia/damage. Diabetes mellitus, a condition characterized by cardiovascular disease, nephropathy, and micro- and macroangiopathy, showed a dysfunction of endothelial progenitor cells. Herein, we review the mechanisms involved in diabetes-related dysfunction of endothelial progenitor cells, highlighting how hyperglycemia affects the different steps of endothelial progenitor cells lifetime (i.e., bone marrow mobilization, trafficking into the bloodstream, differentiation in endothelial cells, and homing in damaged tissues/organs). Finally, we review preclinical and clinical strategies that aim to revert diabetes-induced dysfunction of endothelial progenitor cells as a means of finding new strategies to prevent diabetic complications.

  9. Strategies to Reverse Endothelial Progenitor Cell Dysfunction in Diabetes

    Directory of Open Access Journals (Sweden)

    Alessandra Petrelli

    2012-01-01

    Full Text Available Bone-marrow-derived cells-mediated postnatal vasculogenesis has been reported as the main responsible for the regulation of vascular homeostasis in adults. Since their discovery, endothelial progenitor cells have been depicted as mediators of postnatal vasculogenesis for their peculiar phenotype (partially staminal and partially endothelial, their ability to differentiate in endothelial cell line and to be incorporated into the vessels wall during ischemia/damage. Diabetes mellitus, a condition characterized by cardiovascular disease, nephropathy, and micro- and macroangiopathy, showed a dysfunction of endothelial progenitor cells. Herein, we review the mechanisms involved in diabetes-related dysfunction of endothelial progenitor cells, highlighting how hyperglycemia affects the different steps of endothelial progenitor cells lifetime (i.e., bone marrow mobilization, trafficking into the bloodstream, differentiation in endothelial cells, and homing in damaged tissues/organs. Finally, we review preclinical and clinical strategies that aim to revert diabetes-induced dysfunction of endothelial progenitor cells as a means of finding new strategies to prevent diabetic complications.

  10. Distinct bone marrow blood vessels differentially regulate haematopoiesis.

    Science.gov (United States)

    Itkin, Tomer; Gur-Cohen, Shiri; Spencer, Joel A; Schajnovitz, Amir; Ramasamy, Saravana K; Kusumbe, Anjali P; Ledergor, Guy; Jung, Yookyung; Milo, Idan; Poulos, Michael G; Kalinkovich, Alexander; Ludin, Aya; Kollet, Orit; Shakhar, Guy; Butler, Jason M; Rafii, Shahin; Adams, Ralf H; Scadden, David T; Lin, Charles P; Lapidot, Tsvee

    2016-04-21

    Bone marrow endothelial cells (BMECs) form a network of blood vessels that regulate both leukocyte trafficking and haematopoietic stem and progenitor cell (HSPC) maintenance. However, it is not clear how BMECs balance these dual roles, and whether these events occur at the same vascular site. We found that mammalian bone marrow stem cell maintenance and leukocyte trafficking are regulated by distinct blood vessel types with different permeability properties. Less permeable arterial blood vessels maintain haematopoietic stem cells in a low reactive oxygen species (ROS) state, whereas the more permeable sinusoids promote HSPC activation and are the exclusive site for immature and mature leukocyte trafficking to and from the bone marrow. A functional consequence of high permeability of blood vessels is that exposure to blood plasma increases bone marrow HSPC ROS levels, augmenting their migration and differentiation, while compromising their long-term repopulation and survival. These findings may have relevance for clinical haematopoietic stem cell transplantation and mobilization protocols.

  11. Numerical analysis of the chimera states in the multilayered network model

    Science.gov (United States)

    Goremyko, Mikhail V.; Maksimenko, Vladimir A.; Makarov, Vladimir V.; Ghosh, Dibakar; Bera, Bidesh K.; Dana, Syamal K.; Hramov, Alexander E.

    2017-03-01

    We numerically study the interaction between the ensembles of the Hindmarsh-Rose (HR) neuron systems, arranged in the multilayer network model. We have shown that the fully identical layers, demonstrated individually different chimera due to the initial mismatch, come to the identical chimera state with the increase of inter-layer coupling. Within the multilayer model we also consider the case, when the one layer demonstrates chimera state, while another layer exhibits coherent or incoherent dynamics. It has been shown that the interactions chimera-coherent state and chimera-incoherent state leads to the both excitation of chimera as from the ensemble of fully coherent or incoherent oscillators, and suppression of initially stable chimera state

  12. Human endothelial precursor cells express tumor endothelial marker 1/endosialin/CD248.

    Science.gov (United States)

    Bagley, Rebecca G; Rouleau, Cecile; St Martin, Thia; Boutin, Paula; Weber, William; Ruzek, Melanie; Honma, Nakayuki; Nacht, Mariana; Shankara, Srinivas; Kataoka, Shiro; Ishida, Isao; Roberts, Bruce L; Teicher, Beverly A

    2008-08-01

    Angiogenesis occurs during normal physiologic processes as well as under pathologic conditions such as tumor growth. Serial analysis of gene expression profiling revealed genes [tumor endothelial markers (TEM)] that are overexpressed in tumor endothelial cells compared with normal adult endothelial cells. Because blood vessel development of malignant tumors under certain conditions may include endothelial precursor cells (EPC) recruited from bone marrow, we investigated TEM expression in EPC. The expression of TEM1 or endosialin (CD248) and other TEM has been discovered in a population of vascular endothelial growth factor receptor 2+/CD31+/CD45-/VE-cadherin+ EPC derived from human CD133+/CD34+ cells. EPC share some properties with fully differentiated endothelial cells from normal tissue, yet reverse transcription-PCR and flow cytometry reveal that EPC express higher levels of endosialin at the molecular and protein levels. The elevated expression of endosialin in EPC versus mature endothelial cells suggests that endosialin is involved in the earlier stages of tumor angiogenesis. Anti-endosialin antibodies inhibited EPC migration and tube formation in vitro. In vivo, immunohistochemistry indicated that human EPC continued to express endosialin protein in a Matrigel plug angiogenesis assay established in nude mice. Anti-endosialin antibodies delivered systemically at 25 mg/kg were also able to inhibit circulating murine EPC in nude mice bearing s.c. SKNAS tumors. EPC and bone marrow-derived cells have been shown previously to incorporate into malignant blood vessels in some instances, yet they remain controversial in the field. The data presented here on endothelial genes that are up-regulated in tumor vasculature and in EPC support the hypothesis that the angiogenesis process in cancer can involve EPC.

  13. Book Review: Evolution's Chimera: Bats and the Marvel of ...

    African Journals Online (AJOL)

    Abstract. Book Title: Evolution's Chimera: Bats and the Marvel of Evolutionary Adaptation. Book Author: David Jacobs. 2016, University of Cape Town Press, Juta and Company (Pty) Ltd, PO Box 14373, Lansdowne 7779, Cape Town, South Africa Softcover, 204 pages. ISBN 978-1-77582-212-7. Price R299 ...

  14. Radiobiological researches on Dianthus caryophyllus L. carnation chimeras

    International Nuclear Information System (INIS)

    Pereau-Leroy, Pierre

    1975-01-01

    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 [fr

  15. La Chimera di Dino Campana e Altre Chimere

    Directory of Open Access Journals (Sweden)

    Lucia Wataghin

    2008-08-01

    Full Text Available O presente artigo contém considerações sobre resultados e problemáticas da reutilização de materiais da tradição literária em um dos mais celebrados poemas de Dino Campana, La Chimera.

  16. What's Wrong with Human/Nonhuman Chimera Research?

    Science.gov (United States)

    Hyun, Insoo

    2016-08-01

    The National Institutes of Health (NIH) is poised to lift its funding moratorium on research involving chimeric human/nonhuman embryos, pending further consideration by an NIH steering committee. The kinds of ethical concerns that seem to underlie this research and chimera research more generally can be adequately addressed.

  17. Use of fragmentation beams at LNS with CHIMERA detector

    Directory of Open Access Journals (Sweden)

    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.

  18. Chimera: construction of chimeric sequences for phylogenetic analysis

    NARCIS (Netherlands)

    Leunissen, J.A.M.

    2003-01-01

    Chimera allows the construction of chimeric protein or nucleic acid sequence files by concatenating sequences from two or more sequence files in PHYLIP formats. It allows the user to interactively select genes and species from the input files. The concatenated result is stored to one single output

  19. Development of cassava periclinal chimera may boost production.

    Science.gov (United States)

    Bomfim, N; Nassar, N M A

    2014-02-10

    Plant periclinal chimeras are genotypic mosaics arranged concentrically. Trials to produce them to combine different species have been done, but pratical results have not been achieved. We report for the second time the development of a very productive interspecific periclinal chimera in cassava. It has very large edible roots up to 14 kg per plant at one year old compared to 2-3 kg in common varieties. The epidermal tissue formed was from Manihot esculenta cultivar UnB 032, and the subepidermal and internal tissue from the wild species, Manihot fortalezensis. We determined the origin of tissues by meiotic and mitotic chromosome counts, plant anatomy and morphology. Epidermal features displayed useful traits to deduce tissue origin: cell shape and size, trichome density and stomatal length. Chimera roots had a wholly tuberous and edible constitution with smaller starch granule size and similar distribution compared to cassava. Root size enlargement might have been due to an epigenetic effect. These results suggest a new line of improved crop based on the development of interspecific chimeras composed of different combinations of wild and cultivated species. It promises boosting cassava production through exceptional root enlargement.

  20. What's Wrong with Human/Nonhuman Chimera Research?

    Directory of Open Access Journals (Sweden)

    Insoo Hyun

    2016-08-01

    Full Text Available The National Institutes of Health (NIH is poised to lift its funding moratorium on research involving chimeric human/nonhuman embryos, pending further consideration by an NIH steering committee. The kinds of ethical concerns that seem to underlie this research and chimera research more generally can be adequately addressed.

  1. Blood and Bone Marrow Transplant?

    Science.gov (United States)

    ... Topics / Blood and Bone Marrow Transplant Blood and Bone Marrow Transplant Also known as Hematopoietic Stem Cell Transplant , Hematopoietic ... person, called a donor, it is an allogeneic transplant. Blood or bone marrow transplants most commonly are used to treat ...

  2. Efficiency of rat bone marrow-derived endothelial progenitor cells on VEGF and SDF-1 expression with the aid of Tanshinone ⅡA%丹参酮ⅡA增效大鼠骨髓源性内皮祖细胞VEGF、SDF-1表达

    Institute of Scientific and Technical Information of China (English)

    杨彦; 陈庆伟; 曹广煜; 李桂琼

    2012-01-01

    Objective:To investigate the effect of rat bone marrow-derived endothelial progenitor cells on VEGF expression with the aid of Tanshinone ⅡA.Methods:The mononuclear cells were isolated from rat femoral and tibial bone marrow using percoll density gradient centrifugation,then induced with vascular endothelial growth factor(VEGF),basic fibroblast growth factor(bFGF) and epidermal growth factor(EGF)for two weeks.The expression of cell markers was assessed by immunocytochemistry,and the attached cells were stained with Dil-acLDL and FITC-UEA-1.Then this study included two groups: EPCs and EPCs+ Tanshinone ⅡA groups.The expression levels of VEGF and SDF-1 was detected by fluorescent qRT-PCR and western blot.Results:Compared with the EPCs group,EPCs+ Tanshinone IIA group had a higher VEGF and SDF-1 expression(P0.05).Conclusions:EPCs can increase VEGF and SDF-1 expression with combination of Tanshinone IIA.Homing rate and repairing efficacy of EPCs can improve also with the aid of Tanshinone IIA.EPCs can increase VEGF and SDF-1 expression in injured myocardium after homing,thus improve angiogenesis efficiently.%目的:研究在丹参酮ⅡA的辅助下,骨髓源性内皮祖细胞(EPCs)VEGF与SDF-1表达是否能增强,从而促进细胞归巢。方法:Percoll密度梯度离心法分离SD大鼠骨髓单个核细胞,血管内皮生长因子(VEGF)、表皮生长因子((EGF)、碱性成纤维细胞生长因子(bFGF)诱导培养,并进行形态学、免疫学(免疫细胞化学染色)、功能学(Dil-acLDL与FITC-UEA-1双荧光染色)鉴定。将鉴定为EPCs的细胞分为单纯EPCs组(对照组)、EPCs+丹参酮ⅡA组(加药组)。细胞培养第9d,Western blot与实时荧光定量PCR检测各组VEGF、SDF-1基因与蛋白表达。结果:EPCs+丹参酮IIA组VEGF、SDF-1基因与蛋白表达均高于EPCs组(p均〈0.05)。结论:丹参酮ⅡA可上调大鼠骨

  3. Bone Marrow Diseases

    Science.gov (United States)

    Bone marrow is the spongy tissue inside some of your bones, such as your hip and thigh bones. It contains stem cells. The stem cells can ... the platelets that help with blood clotting. With bone marrow disease, there are problems with the stem ...

  4. UVB pretreatment of rat bone marrow allografts. Prevention of GVHD and induction of allochimerism and donor-specific unresponsiveness

    International Nuclear Information System (INIS)

    Chabot, J.A.; Pepino, P.; Wasfie, T.; Stegall, M.D.; Marboe, C.; Hardy, M.A.

    1990-01-01

    Ultraviolet B irradiation has been used to pretreat blood and islets to prevent subsequent graft rejection. In this study the optimal dose of UVB irradiation of bone marrow was determined in syngeneic recipients and was subsequently applied to in-vitro treatment of bone marrow allografts. UVB pretreatment of donor bone marrow inoculum led to complete prevention of GVHD in allogeneic rat recipients without major marrow or other toxicity. Long-standing recipients of allogeneic UVB-BM became stable adult chimeras. The recipients of allogeneic BM were populated by donor-type peripheral blood lymphocytes and did not reject host or donor-type heart grafts. The BM allograft recipients were immunocompetent as measured by their ability to normally reject third-party cardiac allografts. We suggest that the prevention of GVHD and induction of stable chimerism in adult recipients of allogeneic UVB-BM may be mediated by suppressor mechanisms

  5. UVB pretreatment of rat bone marrow allografts. Prevention of GVHD and induction of allochimerism and donor-specific unresponsiveness

    Energy Technology Data Exchange (ETDEWEB)

    Chabot, J.A.; Pepino, P.; Wasfie, T.; Stegall, M.D.; Marboe, C.; Hardy, M.A. (Columbia Univ. College of Physicians and Surgeons, New York, NY (USA))

    1990-05-01

    Ultraviolet B irradiation has been used to pretreat blood and islets to prevent subsequent graft rejection. In this study the optimal dose of UVB irradiation of bone marrow was determined in syngeneic recipients and was subsequently applied to in-vitro treatment of bone marrow allografts. UVB pretreatment of donor bone marrow inoculum led to complete prevention of GVHD in allogeneic rat recipients without major marrow or other toxicity. Long-standing recipients of allogeneic UVB-BM became stable adult chimeras. The recipients of allogeneic BM were populated by donor-type peripheral blood lymphocytes and did not reject host or donor-type heart grafts. The BM allograft recipients were immunocompetent as measured by their ability to normally reject third-party cardiac allografts. We suggest that the prevention of GVHD and induction of stable chimerism in adult recipients of allogeneic UVB-BM may be mediated by suppressor mechanisms.

  6. Expression of antigens coded in murine leukemia viruses on thymocytes of allogeneic donor origin in AKR mice following syngeneic or allogeneic bone marrow transplantation

    International Nuclear Information System (INIS)

    Wustrow, T.P.; Good, R.A.

    1985-01-01

    Removal of T-lymphocytes from marrow inoculum with monoclonal antibody plus complement permitted establishment of long-lived allogeneic chimeras between C57BL/6 and AKR/J mice. Development of leukemia was prevented for 15 mo. Protection from leukemia occurred with both young (4 wk) and older (4 mo) recipients. AKR mice reconstituted with syngeneic marrow or control AKR mice all developed leukemia-lymphoma before 1 yr of age. During spontaneous lymphomagenesis in AKR mice, amplified expression of gag or env gene-coded virus antigens on the surface of thymocytes preceded leukemia development and evidence for amplification of other virus genes. These changes generally appeared before 6 mo. Similar viral gene expression and viral gene amplification occurred in the thymus and spleen cells of leukemia-resistant chimeric mice. Using monoclonal antibodies to Mr 70,000 glycoprotein epitopes characteristic of ecotropic, xenotropic, or dualtropic viruses, antigens marking each virus form were found on thymocytes of allogeneic 4-wk and 4-mo chimeras as well as on the cells of AKR mice and of AKR mice reconstituted with syngeneic marrow. Flow cytometric analysis showed amplification of the virus genes in mice protected from leukemia-lymphoma by allogeneic bone marrow transplantation from leukemia-resistant mice. Allogeneic chimeras and syngeneically transplanted mice both showed evidence of accelerated viremia and of recombinant virus formation. The findings suggest that an event essential to leukemogenesis which occurs within the AKR lymphoid cells or their environment is lacking in the allogeneic chimeras. The nature of this influence of a resistance gene or genes introduced into AKR mice by allogeneic bone marrow transplantation deserves further study

  7. Stable amplitude chimera states in a network of locally coupled Stuart-Landau oscillators

    Science.gov (United States)

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

    2018-03-01

    We investigate the occurrence of collective dynamical states such as transient amplitude chimera, stable amplitude chimera, and imperfect breathing chimera states in a locally coupled network of Stuart-Landau oscillators. In an imperfect breathing chimera state, the synchronized group of oscillators exhibits oscillations with large amplitudes, while the desynchronized group of oscillators oscillates with small amplitudes, and this behavior of coexistence of synchronized and desynchronized oscillations fluctuates with time. Then, we analyze the stability of the amplitude chimera states under various circumstances, including variations in system parameters and coupling strength, and perturbations in the initial states of the oscillators. For an increase in the value of the system parameter, namely, the nonisochronicity parameter, the transient chimera state becomes a stable chimera state for a sufficiently large value of coupling strength. In addition, we also analyze the stability of these states by perturbing the initial states of the oscillators. We find that while a small perturbation allows one to perturb a large number of oscillators resulting in a stable amplitude chimera state, a large perturbation allows one to perturb a small number of oscillators to get a stable amplitude chimera state. We also find the stability of the transient and stable amplitude chimera states and traveling wave states for an appropriate number of oscillators using Floquet theory. In addition, we also find the stability of the incoherent oscillation death states.

  8. Role of marrow architecture and stromal cells in the recovery process of aplastic marrow of lethally irradiated rats parabiosed with healthy litter mates

    International Nuclear Information System (INIS)

    Hayashi, K.; Kagawa, K.; Awai, M.; Irino, S.

    1986-01-01

    Bone marrow aplasia was induced in rats by whole body lethal irradiation (1,000 rads by x-ray), and rats died of irradiation injury within 7 days. Correlative studies at light (LM), transmission (TEM) and scanning electron microscopy (SEM) demonstrated swelling of endothelial and reticular cells and hemorrhage due to detachment of sinus endothelial cells on days 1 and 2. With time, structural recovery occurred without hemopoietic recovery. Reticular cells developed small intracytoplasmic lipid droplets on days 3 and 4. This resulted in fatty aplastic marrow within 7 days. On the other hand, in the marrow of irradiated rats parabiosed with healthy mates by aortic anastomosis, hemopoiesis was initiated by adhesion of nucleated blood cells to fine cytoplasmic pseudopods of fat-stored cells on days 1 and 2 after parabiosis. On days 3 to 5, reticular cells with large lipid droplets and fine pseudopods increased, then hemopoietic foci became clear and extensive. On day 8 after parabiosis, the aplastic bone marrow recovered completely both its structure and hemopoietic activity. Thus, hemopoietic recovery in lethally irradiated marrow begins with recovery of vascular endothelial cells, re-establishment of sinusoidal structure, and morphological and functional recoveries of reticular cells from fat-storage cells by releasing intracytoplasmic lipid droplets. Marrow stromal cells, namely reticular, fat-storage and fibroblastoid cells, share a common cellular origin, and regain their structure and function when fat-storage cells and fibroid cells are placed in contact with hemopoietic precursor cells

  9. Graft rejection by cytolytic T cells. Specificity of the effector mechanism in the rejection of allogeneic marrow

    International Nuclear Information System (INIS)

    Nakamura, H.; Gress, R.E.

    1990-01-01

    Cellular effector mechanisms of allograft rejection remain incompletely described. Characterizing the rejection of foreign-marrow allografts rather than solid-organ grafts has the advantage that the cellular composition of the marrow graft, as a single cell suspension, can be altered to include cellular components with differing antigen expression. Rejection of marrow grafts is sensitive to lethal doses of radiation in the mouse but resistant to sublethal levels of radiation. In an effort to identify cells mediating host resistance, lymphocytes were isolated and cloned from spleens of mice 7 days after sublethal TBI (650 cGy) and inoculation with allogeneic marrow. All clones isolated were cytolytic with specificity for MHC encoded gene products of the allogeneic marrow donor. When cloned cells were transferred in vivo into lethally irradiated (1025 cGy) recipients unable to reject allogeneic marrow, results utilizing splenic 125IUdR uptake indicated that these MHC-specific cytotoxic clones could suppress marrow proliferation. In order to characterize the effector mechanism and the ability of the clones to affect final engraftment, double donor chimeras were constructed so that 2 target cell populations differing at the MHC from each other and from the host were present in the same marrow allograft. Results directly demonstrated an ability of CTL of host MHC type to mediate graft rejection and characterized the effector mechanism as one with specificity for MHC gene products

  10. Bone - marrow postirradiation syndrome

    International Nuclear Information System (INIS)

    Sesztakova, E.; Bilek, J.; Benova, K.; Novakova, J.; Culenova, K.

    2006-01-01

    Quantitative and qualitative changes in haemopoietic cells in chicken bone Marrow were investigated after acute single irradiation with doses 4.5 Gy and 5 Gy. Samples of bone marrow were obtained from proximal femoral epiphysis of decapitated chickens. Marrow smears were prepared and stained according to Pappenheim. Qualitative examination of myelogram showed proliferation of adipose tissue, hypocellularity, caryolyosis, caryorexis, disintegration of cells and proliferation of cells which could not be differentiated. Quantitative examination revealed high radiosensitivity of blast cells and lymphocytes shortly after irradiation. (authors)

  11. Bone marrow transplantation

    International Nuclear Information System (INIS)

    Storb, R.; Santos, G.W.

    1979-01-01

    Bone marrow transplantation has been increasingly used to treat patients with severe combined immunodeficiency diseases, severe aplastic anemia, and malignant hematologic diseases, especially leukemia. At the Workshop a number of problems were discussed, e.g., conditioning regimens aimed at overcoming the problem of marrow graft rejection and reducing the incidence of recurrent leukemia, prevention of graft-versus-host disease (GVHD), possible mechanisms involved in stable graft-host tolerance, graft-versus-leukemia effect in mice, and finally, the possible use of autologous marrow transplantation

  12. Chimera regimes in a ring of oscillators with local nonlinear interaction

    Science.gov (United States)

    Shepelev, Igor A.; Zakharova, Anna; Vadivasova, Tatiana E.

    2017-03-01

    One of important problems concerning chimera states is the conditions of their existence and stability. Until now, it was assumed that chimeras could arise only in ensembles with nonlocal character of interactions. However, this assumption is not exactly right. In some special cases chimeras can be realized for local type of coupling [1-3]. We propose a simple model of ensemble with local coupling when chimeras are realized. This model is a ring of linear oscillators with the local nonlinear unidirectional interaction. Chimera structures in the ring are found using computer simulations for wide area of values of parameters. Diagram of the regimes on plane of control parameters is plotted and scenario of chimera destruction are studied when the parameters are changed.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Targeting nanodisks via a single chain variable antibody - Apolipoprotein chimera

    International Nuclear Information System (INIS)

    Iovannisci, David M.; Beckstead, Jennifer A.; Ryan, Robert O.

    2009-01-01

    Nanodisks (ND) are nanometer scale complexes of phospholipid and apolipoprotein that have been shown to function as drug delivery vehicles. ND harboring significant quantities of the antifungal agent, amphotericin B, or the bioactive isoprenoid, all trans retinoic acid, have been generated and characterized. As currently formulated, ND possess limited targeting capability. In this study, we constructed a single chain variable antibody (scFv).apolipoprotein chimera and assessed the ability of this fusion protein to form ND and recognize the antigen to which the scFv is directed. Data obtained revealed that α-vimentin scFv.apolipoprotein A-I is functional in ND formation and antigen recognition, opening the door to the use of such chimeras in targeting drug-enriched ND to specific tissues.

  15. Bone marrow transplant

    Science.gov (United States)

    ... Arrange medical leave from work Take care of bank or financial statements Arrange care of pets Arrange ... Bleeding during cancer treatment Bone marrow transplant - discharge Central venous catheter - dressing change Central venous catheter - flushing ...

  16. Icing modelling in NSMB with chimera overset grids

    Energy Technology Data Exchange (ETDEWEB)

    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. Bone marrow and bone marrow derived mononuclear stem cells therapy for the chronically ischemic myocardium

    International Nuclear Information System (INIS)

    Waksman, Ron; Baffour, Richard

    2003-01-01

    Bone marrow stem cells have been shown to differentiate into various phenotypes including cardiomyocytes, vascular endothelial cells and smooth muscle. Bone marrow stem cells are mobilized and home in to areas of injured myocardium where they are involved in tissue repair. In addition, bone marrow secretes multiple growth factors, which are essential for angiogenesis and arteriogenesis. In some patients, these processes are not enough to avert clinical symptoms of ischemic disease. Therefore, in vivo administration of an adequate number of stem cells would be a significant therapeutic advance. Unfractionated bone marrow derived mononuclear stem cells, which contain both hematopoietic and nonhematopoietic cells may be more appropriate for cell therapy. Studies in animal models suggest that implantation of different types of stem cells improve angiogenesis and arteriogenesis, tissue perfusion as well as left ventricular function. Several unanswered questions remain. For example, the optimal delivery approach, dosage and timing of the administration of cell therapy as well as durability of improvements need to be studied. Early clinical studies have demonstrated safety and feasibility of various cell therapies in ischemic disease. Randomized, double blind and placebo-controlled clinical trials need to be completed to determine the effectiveness of stem cell

  18. Radiobiological research on carnation chimerae Dianthus Caryophyllus L

    International Nuclear Information System (INIS)

    Pereau-Leroy, Pierre.

    1975-01-01

    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 [fr

  19. Anticipatory Governance: Bioethical Expertise for Human/Animal Chimeras

    Science.gov (United States)

    Harvey, Alison; Salter, Brian

    2012-01-01

    The governance demands generated by the use of human/animal chimeras in scientific research offer both a challenge and an opportunity for the development of new forms of anticipatory governance through the novel application of bioethical expertise. Anticipatory governance can be seen to have three stages of development whereby bioethical experts move from a reactive to a proactive stance at the edge of what is scientifically possible. In the process, the ethicists move upstream in their engagement with the science of human-to-animal chimeras. To what extent is the anticipatory coestablishment of the principles and operational rules of governance at this early stage in the development of the human-to-animal research field likely to result in a framework for bioethical decision making that is in support of science? The process of anticipatory governance is characterised by the entwining of the scientific and the philosophical so that judgements against science are also found to be philosophically unfounded, and conversely, those activities that are permissible are deemed so on both scientific and ethical grounds. Through what is presented as an organic process, the emerging bioethical framework for human-to-animal chimera research becomes a legitimating framework within which ‘good’ science can safely progress. Science gives bioethical expertise access to new governance territory; bioethical expertise gives science access to political acceptability. PMID:23576848

  20. Multiclustered chimeras in large semiconductor laser arrays with nonlocal interactions

    Science.gov (United States)

    Shena, J.; Hizanidis, J.; Hövel, P.; Tsironis, G. P.

    2017-09-01

    The dynamics of a large array of coupled semiconductor lasers is studied numerically for a nonlocal coupling scheme. Our focus is on chimera states, a self-organized spatiotemporal pattern of coexisting coherence and incoherence. In laser systems, such states have been previously found for global and nearest-neighbor coupling, mainly in small networks. The technological advantage of large arrays has motivated us to study a system of 200 nonlocally coupled lasers with respect to the emerging collective dynamics. Moreover, the nonlocal nature of the coupling allows us to obtain robust chimera states with multiple (in)coherent domains. The crucial parameters are the coupling strength, the coupling phase and the range of the nonlocal interaction. We find that multiclustered chimera states exist in a wide region of the parameter space and we provide quantitative characterization for the obtained spatiotemporal patterns. By proposing two different experimental setups for the realization of the nonlocal coupling scheme, we are confident that our results can be confirmed in the laboratory.

  1. Bone marrow transplantation immunology

    International Nuclear Information System (INIS)

    Trentin, J.J.; Kiessling, R.; Wigzell, H.; Gallagher, M.T.; Datta, S.K.; Kulkarni, S.S.

    1977-01-01

    Tests were made to determine whether genetic resistance (GR) to bone marrow transplantation represents a natural lymphoma-leukemia defense mechanism, as follows: (C57 x AKR) F 1 hybrid mice show GR to C57 parental bone marrow cells, but not to AKR parental bone marrow cells (C3H x AKR) F 1 hybrids show no GR to bone marrow transplantation from either parental strain. However, transplantation of AKR lymphoma cells into lethally irradiated ''resistant'' (C57 x AKR) F 1 and ''nonresistant'' (C3H x AKR) F 1 hybrids produced lymphomatous spleen colonies in ''nonresistant'' hybrids but not in ''resistant'' hybrids. Thus ''resistant'' (C57 x AKR) F 1 hybrids can recognize and reject AKR lymphoma cells, but not normal AKR bone marrow cells. A normal biologic role of leukemia-lymphoma surveillance was postulated for genetic resistance to marrow transplantation, directed at antigens which, like TL, are expressed on normal hemopoietic cells of some strains, but only on leukemic cells of other strains

  2. Chimera states and the interplay between initial conditions and non-local coupling

    Science.gov (United States)

    Kalle, Peter; Sawicki, Jakub; Zakharova, Anna; Schöll, Eckehard

    2017-03-01

    Chimera states are complex spatio-temporal patterns that consist of coexisting domains of coherent and incoherent dynamics. We study chimera states in a network of non-locally coupled Stuart-Landau oscillators. We investigate the impact of initial conditions in combination with non-local coupling. Based on an analytical argument, we show how the coupling phase and the coupling strength are linked to the occurrence of chimera states, flipped profiles of the mean phase velocity, and the transition from a phase- to an amplitude-mediated chimera state.

  3. Simple and complex chimera states in a nonlinearly coupled oscillatory medium

    Science.gov (United States)

    Bolotov, Maxim; Smirnov, Lev; Osipov, Grigory; Pikovsky, Arkady

    2018-04-01

    We consider chimera states in a one-dimensional medium of nonlinear nonlocally coupled phase oscillators. In terms of a local coarse-grained complex order parameter, the problem of finding stationary rotating nonhomogeneous solutions reduces to a third-order ordinary differential equation. This allows finding chimera-type and other inhomogeneous states as periodic orbits of this equation. Stability calculations reveal that only some of these states are stable. We demonstrate that an oscillatory instability leads to a breathing chimera, for which the synchronous domain splits into subdomains with different mean frequencies. Further development of instability leads to turbulent chimeras.

  4. Persistence of antigen is required to maintain transplantation tolerance induced by genetic modification of bone marrow stem cells.

    Science.gov (United States)

    Tian, C; Bagley, J; Iacomini, J

    2006-09-01

    Genetic modification of hematopoietic stem cells (HSCs) resulting in a state of molecular chimerism can be used to induce donor-specific tolerance to allografts. However, the requirements for maintaining tolerance in molecular chimeras remain unknown. Here, we examined whether long-term expression of a retrovirally encoded alloantigen in hematopoietic cells is required to maintain donor-specific tolerance in molecular chimeras. To this end, mice were reconstituted with syngeneic bone marrow transduced with retroviruses carrying the gene encoding the allogeneic MHC class I molecule Kb. Following induction of molecular chimerism, mice were depleted of cells expressing Kb by administration of the anti-Kb monoclonal antibody Y-3. Mice that were effectively depleted of cells expressing the retrovirally encoded MHC class I antigen rejected Kb disparate skin allografts. In contrast, control molecular chimeras accepted Kb disparate skin allografts indefinitely. These data suggest maintenance of tolerance in molecular chimeras requires long-term expression of retrovirally transduced alloantigen on the progeny of retrovirally transduced HSCs.

  5. Myeloid-Epithelial-Reproductive Receptor Tyrosine Kinase and Milk Fat Globule Epidermal Growth Factor 8 Coordinately Improve Remodeling After Myocardial Infarction via Local Delivery of Vascular Endothelial Growth Factor.

    Science.gov (United States)

    Howangyin, Kiave-Yune; Zlatanova, Ivana; Pinto, Cristina; Ngkelo, Anta; Cochain, Clément; Rouanet, Marie; Vilar, José; Lemitre, Mathilde; Stockmann, Christian; Fleischmann, Bernd K; Mallat, Ziad; Silvestre, Jean-Sébastien

    2016-03-01

    In infarcted heart, improper clearance of dying cells by activated neighboring phagocytes may precipitate the transition to heart failure. We analyzed the coordinated role of 2 major mediators of efferocytosis, the myeloid-epithelial-reproductive protein tyrosine kinase (Mertk) and the milk fat globule epidermal growth factor (Mfge8), in directing cardiac remodeling by skewing the inflammatory response after myocardial infarction. We generated double-deficient mice for Mertk and Mfge8 (Mertk(-/-)/Mfge8(-/-)) and challenged them with acute coronary ligature. Compared with wild-type, Mertk-deficient (Mertk(-/-)), or Mfge8-deficient (Mfge8(-/-)) animals, Mertk(-/-)/Mfge8(-/-) mice displayed greater alteration in cardiac function and remodeling. Mertk and Mfge8 were expressed mainly by cardiac Ly6C(High and Low) monocytes and macrophages. In parallel, Mertk(-/-)/Mfge8(-/-) bone marrow chimeras manifested increased accumulation of apoptotic cells, enhanced fibrotic area, and larger infarct size, as well as reduced angiogenesis. We found that the abrogation of efferocytosis affected neither the ability of circulating monocytes to infiltrate cardiac tissue nor the number of resident Ly6C(High) and Ly6C(How) monocytes/macrophages populating the infarcted milieu. In contrast, combined Mertk and Mfge8 deficiency in Ly6C(High)/Ly6C(Low) monocytes/macrophages either obtained from in vitro differentiation of bone marrow cells or isolated from infarcted hearts altered their capacity of efferocytosis and subsequently blunted vascular endothelial growth factor A (VEGFA) release. Using LysMCre(+)/VEGFA(fl/fl) mice, we further identified an important role for myeloid-derived VEGFA in improving cardiac function and angiogenesis. After myocardial infarction, Mertk- and Mfge8-expressing monocyte/macrophages synergistically engage the clearance of injured cardiomyocytes, favoring the secretion of VEGFA to locally repair the dysfunctional heart. © 2016 The Authors.

  6. Marrow transfusions into normal recipients

    International Nuclear Information System (INIS)

    Brecher, G.

    1983-01-01

    During the past several years we have explored the transfusion of bone marrow into normal nonirradiated mice. While transfused marrow proliferates readily in irradiated animals, only minimal proliferation takes place in nonirradiated recipients. It has generally been assumed that this was due to the lack of available proliferative sites in recipients with normal marrow. Last year we were able to report that the transfusion of 200 million bone marrow cells (about 2/3 of the total complement of marrow cells of a normal mouse) resulted in 20% to 25% of the recipient's marrow being replaced by donor marrow. Thus we can now study the behavior of animals that have been transfused (donor) and endogenous (recipient) marrow cells, although none of the tissues of either donor or recipient have been irradiated. With these animals we hope to investigate the nature of the peculiar phenomenon of serial exhaustion of marrow, also referred to as the limited self-replicability of stem cells

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

    Science.gov (United States)

    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.

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

    International Nuclear Information System (INIS)

    Bick, Christian; Ashwin, Peter

    2016-01-01

    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. (paper)

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

    International Nuclear Information System (INIS)

    Weiden, P.L.; Storb, R.; Tsoi, M.S.; Graham, T.C.; Lerner, K.G.; Thomas, E.D.

    1976-01-01

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    Hart, Joseph D. [Institute for Research in Electronics and Applied Physics, University of Maryland, College Park, Maryland 20742 (United States); Department of Physics, University of Maryland, College Park, Maryland 20742 (United States); Bansal, Kanika [Department of Mathematics, University at Buffalo, SUNY Buffalo, New York 14260 (United States); US Army Research Laboratory, Aberdeen Proving Ground, Maryland 21005 (United States); Murphy, Thomas E. [Institute for Research in Electronics and Applied Physics, University of Maryland, College Park, Maryland 20742 (United States); Department of Electrical and Computer Engineering, University of Maryland, College Park, Maryland 20742 (United States); Roy, Rajarshi [Institute for Research in Electronics and Applied Physics, University of Maryland, College Park, Maryland 20742 (United States); Department of Physics, University of Maryland, College Park, Maryland 20742 (United States); Institute for Physical Science and Technology, University of Maryland, College Park, Maryland 20742 (United States)

    2016-09-15

    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. We use a unified approach to determine the stability of all the observed partially synchronous patterns, highlighting the close relationship between chimera and cluster states as belonging to the broader phenomenon of partial synchronization. Our approach is general in terms of network size and connectivity. We also find that chimera states often appear in regions of multistability between global, cluster, and desynchronized states.

  11. Interordinal chimera formation between medaka and zebrafish for analyzing stem cell differentiation.

    Science.gov (United States)

    Hong, Ni; Chen, Songlin; Ge, Ruowen; Song, Jianxing; Yi, Meisheng; Hong, Yunhan

    2012-08-10

    Chimera formation is a standard test for pluripotency of stem cells in vivo. Interspecific chimera formation between distantly related organisms offers also an attractive approach for propagating endangered species. Parameters influencing interspecies chimera formation have remained poorly elucidated. Here, we report interordinal chimera formation between medaka and zebrafish, which separated ∼320 million years ago and exhibit a more than 2-fold difference in developmental speed. We show that, on transplantation into zebrafish blastulae, both noncultivated blastomeres and long-term cultivated embryonic stem (ES) cells of medaka adopted the zebrafish developmental program and differentiated into physiologically functional cell types including pigment cells, blood cells, and cardiomyocytes. We also show that medaka ES cells express differentiation gene markers during chimeric embryogenesis. Therefore, the evolutionary distance and different embryogenesis speeds do not produce donor-host incompatibility to compromise chimera formation between medaka and zebrafish, and molecular markers are valuable for analyzing lineage commitment and cell differentiation in interspecific chimeric embryos.

  12. Targeted chimera delivery to ovarian cancer cells by heterogeneous gold magnetic nanoparticle

    Science.gov (United States)

    Chen, Yao; Xu, Mengjiao; Guo, Yi; Tu, Keyao; Wu, Weimin; Wang, Jianjun; Tong, Xiaowen; Wu, Wenjuan; Qi, Lifeng; Shi, Donglu

    2017-01-01

    Efficient delivery of small interfering RNAs (siRNAs) to the targeted cells has remained a significant challenge in clinical applications. In the present study, we developed a novel aptamer-siRNA chimera delivery system mediated by cationic Au-Fe3O4 nanoparticles (NPs). The chimera constructed by VEGF RNA aptamer and Notch3 siRNA was bonded with heterogeneous Au-Fe3O4 nanoparticles by electrostatic interaction. The obtained complex exhibited much higher silencing efficiency against Notch3 gene compared with chimera alone and lipofectamine-siRNA complex, and improved the antitumor effects of the loaded chimera. Moreover, the efficient delivery of the chimera by Au-Fe3O4 NPs could reverse multi-drug resistance (MDR) of ovarian cancer cells against the chemotherapeutic drug cisplatin, indicating its potential capability for future targeted cancer therapy while overcoming MDR.

  13. Young endothelial cells revive aging blood.

    Science.gov (United States)

    Chang, Vivian Y; Termini, Christina M; Chute, John P

    2017-11-01

    The hematopoietic system declines with age, resulting in decreased hematopoietic stem cell (HSC) self-renewal capacity, myeloid skewing, and immune cell depletion. Aging of the hematopoietic system is associated with an increased incidence of myeloid malignancies and a decline in adaptive immunity. Therefore, strategies to rejuvenate the hematopoietic system have important clinical implications. In this issue of the JCI, Poulos and colleagues demonstrate that infusions of bone marrow (BM) endothelial cells (ECs) from young mice promoted HSC self-renewal and restored immune cell content in aged mice. Additionally, delivery of young BM ECs along with HSCs following total body irradiation improved HSC engraftment and enhanced survival. These results suggest an important role for BM endothelial cells (ECs) in regulating hematopoietic aging and support further research to identify the rejuvenating factors elaborated by BM ECs that restore HSC function and the immune repertoire in aged mice.

  14. A murine model of graft-versus-host disease induced by allogeneic bone marrow transplantation

    International Nuclear Information System (INIS)

    Hu Jiangwei; Jin Jiangang; Ning Hongmei; Yu Liquan; Feng Kai; Chen Hu; Wang Lisha

    2007-01-01

    Objective: To establish the model of graft-versus-host disease (GVHD) in mice with allogeneic bone marrow transplantation. Methods: Bone marrow cells were combined with spleen cells of male donor C57BL/6 mice according to different proportions, then were transfused into female postradiation recipient BALB/c mice. General state, life span and histopathology of the recipient mice and detected chimera were observed. Results and Conclusion:The recipient mice groups which accepted above 5 x 10 6 donor spleen cells developed acute GVHD after different peroids of time. The GVHD model in mice after allo-BMT was successfully established. The transfusion of 5 x 10 6 -5 x 10 7 spleen cells may be adequate to establish the murine model of GVHD for the prevention and treatment of GVHD. The number of murine spleen cells can be chosen according to the experimental requirement. (authors)

  15. Proliferation differentiation and therapeutic effect of short-term cultured murine bone marrow cells

    International Nuclear Information System (INIS)

    Zhao Zekun; Cong Jianbo

    1986-01-01

    Murine bone marrow cells were cultured in conditioned medium of muscle. After 24 hours of culture, both adherent and suspended cells appeared in the culture. The adherent cells mainly consisted of macrophages and the suspended cells were predominantly granulocytes. After 6 days, the total number of nucleated cells and CFU-C in the culture increased about 400% and 600% respectively, but CFU-S reduced to 21% approximately. Lymphocytes persisted only for 4 days. The stem cells (CFU-S) from 6-day culture were injected into the lethally irradiated syngenic mice. The 30 day survival rate of the treated mice was 89% whereas that of the controls was only 7%. The bone marrow cells in 2/8 of recipients sacrificed at 30 or 60 days were of donor type and 6/8 of the recipients were chimeras

  16. Periodic synchronization and chimera in conformist and contrarian oscillators

    Science.gov (United States)

    Hong, Hyunsuk

    2014-06-01

    We consider a system of phase oscillators that couple with both attractive and repulsive interaction under a pinning force and explore collective behavior of the system. The oscillators can be divided into two subpopulations of "conformist" oscillators with attractive interaction and "contrarian" ones with repulsive interaction. We find that the interplay between the pinning force and the opposite relationship of the conformist and contrarian oscillators induce peculiar dynamic states: periodic synchronization, breathing chimera, and fully pinned state depending on the fraction of the conformists. Using the Watanabe-Strogatz transformation, we reduce the dynamics into a low-dimensional one and find that the above dynamic states are generated from the reduced dynamics.

  17. Interspecific in vitro assay for the chimera-forming ability of human pluripotent stem cells.

    Science.gov (United States)

    Masaki, Hideki; Kato-Itoh, Megumi; Umino, Ayumi; Sato, Hideyuki; Hamanaka, Sanae; Kobayashi, Toshihiro; Yamaguchi, Tomoyuki; Nishimura, Ken; Ohtaka, Manami; Nakanishi, Mahito; Nakauchi, Hiromitsu

    2015-09-15

    Functional assay limitations are an emerging issue in characterizing human pluripotent stem cells (PSCs). With rodent PSCs, chimera formation using pre-implantation embryos is the gold-standard assay of pluripotency (competence of progeny to differentiate into all three germ layers). In human PSCs (hPSCs), however, this can only be monitored via teratoma formation or in vitro differentiation, as ethical concerns preclude generation of human-human or human-animal chimeras. To circumvent this issue, we developed a functional assay utilizing interspecific blastocyst injection and in vitro culture (interspecies in vitro chimera assay) that enables the development and observation of embryos up to headfold stage. The assay uses mouse pre-implantation embryos and rat, monkey and human PSCs to create interspecies chimeras cultured in vitro to the early egg-cylinder stage. Intra- and interspecific chimera assays with rodent PSC lines were performed to confirm the consistency of results in vitro and in vivo. The behavior of chimeras developed in vitro appeared to recapitulate that of chimeras developed in vivo; that is, PSC-derived cells survived and were integrated into the epiblast of egg-cylinder-stage embryos. This indicates that the interspecific in vitro chimera assay is useful in evaluating the chimera-forming ability of rodent PSCs. However, when human induced PSCs (both conventional and naïve-like types) were injected into mouse embryos and cultured, some human cells survived but were segregated; unlike epiblast-stage rodent PSCs, they never integrated into the epiblast of egg-cylinder-stage embryos. These data suggest that the mouse-human interspecies in vitro chimera assay does not accurately reflect the early developmental potential/process of hPSCs. The use of evolutionarily more closely related species as host embryos might be necessary to evaluate the developmental potency of hPSCs. © 2015. Published by The Company of Biologists Ltd.

  18. Tie-1-directed expression of Cre recombinase in endothelial cells of embryoid bodies and transgenic mice

    DEFF Research Database (Denmark)

    Gustafsson, E; Brakebusch, C; Hietanen, K

    2001-01-01

    Tissue-specific gene inactivation using the Cre-loxP system has become an important tool to unravel functions of genes when the conventional null mutation is lethal. We report here the generation of a transgenic mouse line expressing Cre recombinase in endothelial cells. In order to avoid...... the production and screening of multiple transgenic lines we used embryonic stem cell and embryoid body technology to identify recombinant embryonic stem cell clones with high, endothelial-specific Cre activity. One embryonic stem cell clone that showed high Cre activity in endothelial cells was used to generate...... germline chimeras. The in vivo efficiency and specificity of the transgenic Cre was analysed by intercrossing the tie-1-Cre line with the ROSA26R reporter mice. At initial stages of vascular formation (E8-9), LacZ staining was detected in almost all cells of the forming vasculature. Between E10 and birth...

  19. Overview of marrow transplantation

    International Nuclear Information System (INIS)

    Thomas, E.D.

    1985-01-01

    Bone marrow transplantation is now an accepted form of therapy for many hematologic disorders including aplastic anemia, genetically determined diseases and malignant diseases, particularly leukemia, and for rescue of patients given intensive chemoradiotherapy for malignant disease. The donor may be a healthy identical twin, a family member or even an unrelated person. Selection is made on the basis of human leukocyte antigen tissue typing. Intensive chemoradiotherapy is used to suppress patients' immune systems to facilitate engraftment and destroy diseased marrow. Transfusion of platelets, erythrocytes and granulocytes (or all of these), antibiotic coverage and protection from infection are necessary during the pancytopenic period. Survival rates vary considerably depending on a patient's disease, clinical state and age. Patients with aplastic anemia transplanted early in the course of their disease have a survival rate of approximately 80%. Patients with acute lymphoblastic leukemia are usually transplanted in a second or subsequent remission and have a survival rate of 25% to 40%. Patients with acute nonlymphoblastic leukemia in remission have survivals ranging from 45% to 70%. More than 200 patients in the chronic phase of chronic granulocytic leukemia have been transplanted with survival ranging from 50% to 70%. Complications of marrow transplantation include marrow graft rejection, graft-versus-host disease, immunologic insufficiency and the possibility of recurrence of the leukemia. 14 references

  20. Bone marrow origin of decidual cell precursors in the pseudopregnant mouse uterus

    International Nuclear Information System (INIS)

    Kearns, M.; Lala, P.K.

    1982-01-01

    Decidual cells are considered to be the endproduct of a hormonally induced transformation of endometrial stromal cells of the uterus. However, the source of these precursors remains unknown. This study of evaluated the possibility of their bone marrow origin by an examination of the H-2 phenotype of decidual cells in pseudopregnant bone marrow chimeras. These chimeras were produced by repopulating lethally irradiated CBA/J female (H-2k) mice with bone marrow from (CBA/J x C57BL/6J) F1 female (H-2kb) mice. Pseudopregnancy was produced with a hormonal regimen followed by an oil-induced decidual stimulus. Chimerism was evaluated radioautographically by an identification of the donor-specific Kb phenotype on cells with an immunolabeling technique with monospecific anti-H-2 serum followed by radioiodinated protein A. The extent of chimerism as indicated by the degree of Kb labeling on decidual cells as well as macrophages contained within the decidual nodules was quantitatively compared with that seen on splenic lymphocytes. Fair to good chimerism, as reflected by labeling for the donor-specific marker (Kb), was seen on splenic lymphocytes and macrophages within the decidual nodules in 6 out of 11 animals. A similar level of chimerism was detected on decidual cells in all but one of these six, in which case this was low. One animal showed low chimerism in the spleen but good chimerism on the decidual cells. The remaining four mice were nonchimeric for all three cell types. These results indicate that decidual cells and macrophages appearing within the decidual nodules of pseudopregnant mice are ultimate descendants of bone marrow cells

  1. Endothelial juxtaposition of distinct adult stem cells activates angiogenesis signaling molecules in endothelial cells.

    Science.gov (United States)

    Mohammadi, Elham; Nassiri, Seyed Mahdi; Rahbarghazi, Reza; Siavashi, Vahid; Araghi, Atefeh

    2015-12-01

    Efficacy of therapeutic angiogenesis needs a comprehensive understanding of endothelial cell (EC) function and biological factors and cells that interplay with ECs. Stem cells are considered the key components of pro- and anti-angiogenic milieu in a wide variety of physiopathological states, and interactions of EC-stem cells have been the subject of controversy in recent years. In this study, the potential effects of three tissue-specific adult stem cells, namely rat marrow-derived mesenchymal stem cells (rBMSCs), rat adipose-derived stem cells (rADSCs) and rat muscle-derived satellite cells (rSCs), on the endothelial activation of key angiogenic signaling molecules, including VEGF, Ang-2, VEGFR-2, Tie-2, and Tie2-pho, were investigated. Human umbilical vein endothelial cells (HUVECs) and rat lung microvascular endothelial cells (RLMECs) were cocultured with the stem cells or incubated with the stem cell-derived conditioned media on Matrigel. Following HUVEC-stem cell coculture, CD31-positive ECs were flow sorted and subjected to western blotting to analyze potential changes in the expression of the pro-angiogenic signaling molecules. Elongation and co-alignment of the stem cells were seen along the EC tubes in the EC-stem cell cocultures on Matrigel, with cell-to-cell dye communication in the EC-rBMSC cocultures. Moreover, rBMSCs and rADSCs significantly improved endothelial tubulogenesis in both juxtacrine and paracrine manners. These two latter stem cells dynamically up-regulated VEGF, Ang-2, VREGR-2, and Tie-2 but down-regulated Tie2-pho and the Tie2-pho/Tie-2 ratio in HUVECs. Induction of pro-angiogenic signaling in ECs by marrow- and adipose-derived MSCs further indicates the significance of stem cell milieu in angiogenesis dynamics.

  2. Secondhand smoke exposure and endothelial stress in children and adolescents.

    Science.gov (United States)

    Groner, Judith A; Huang, Hong; Nagaraja, Haikady; Kuck, Jennifer; Bauer, John Anthony

    2015-01-01

    Links between secondhand smoke exposure and cardiovascular disease in adults are well established. Little is known about the impact of this exposure on cardiovascular status during childhood. The purpose of this study was to investigate relationships between secondhand smoke exposure in children and adolescents and cardiovascular disease risk--systemic inflammation, endothelial stress, and endothelial repair. A total of 145 subjects, aged 9 to 18 years, were studied. Tobacco smoke exposure was determined by hair nicotine level. Cardiovascular risk was assessed by markers of systemic inflammation (C-reactive protein [CRP] and adiponectin); by soluble intercellular adhesion molecule 1 (s-ICAM1), which measures endothelial activation after surface vascular injury; and by endothelial repair. This was measured by prevalence of endothelial progenitor cells (EPCs), which are bone marrow-derived cells that home preferentially to sites of vascular damage. Hair nicotine was directly correlated with s-ICAM1 (r = 0.4090, P Secondhand smoke exposure during childhood and adolescence is detrimental to vascular health because s-ICAM1 is a marker for endothelial activation and stress after vascular surface injury, and EPCs contribute to vascular repair. The fact that body mass index is also a factor in the model predicting s-ICAM1 is concerning, in that 2 risk factors may both contribute to endothelial stress. Copyright © 2015 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

  3. Chimera patterns in two-dimensional networks of coupled neurons

    Science.gov (United States)

    Schmidt, Alexander; Kasimatis, Theodoros; Hizanidis, Johanne; Provata, Astero; Hövel, Philipp

    2017-03-01

    We discuss synchronization patterns in networks of FitzHugh-Nagumo and leaky integrate-and-fire oscillators coupled in a two-dimensional toroidal geometry. A common feature between the two models is the presence of fast and slow dynamics, a typical characteristic of neurons. Earlier studies have demonstrated that both models when coupled nonlocally in one-dimensional ring networks produce chimera states for a large range of parameter values. In this study, we give evidence of a plethora of two-dimensional chimera patterns of various shapes, including spots, rings, stripes, and grids, observed in both models, as well as additional patterns found mainly in the FitzHugh-Nagumo system. Both systems exhibit multistability: For the same parameter values, different initial conditions give rise to different dynamical states. Transitions occur between various patterns when the parameters (coupling range, coupling strength, refractory period, and coupling phase) are varied. Many patterns observed in the two models follow similar rules. For example, the diameter of the rings grows linearly with the coupling radius.

  4. Provocation of skin graft rejection across murine class II differences by non--bone-marrow-derived cells

    International Nuclear Information System (INIS)

    Stuart, P.M.; Beck-Maier, B.; Melvold, R.W.

    1984-01-01

    We have evaluated the relative contribution of bone-marrow-derived cells to skin allograft immunogenicity in mice differing only at class II major histocompatibility genes by using bone marrow radiation chimeras as donors. The mouse strains used were C57BL/6Kh (B6) and B6.C-H-2bm12 (bm12), which differ only at at A beta gene of the I region of the mouse H-2 complex. Our results demonstrated that skin from (B6----bm12) chimeras was accepted by bm12 recipients and rejected by B6 mice in a manner indistinguishable from that of normal bm12 skin. Likewise, naive bm12 mice rejected (bm12----B6) chimeric skin and normal B6 skin equally well, and B6 animals accepted both types of skin grafts. Our data argues that the donor cell-type leading to graft rejection across limited I region differences is not of bone marrow origin, and that these cells must--at least under certain circumstances--express class II antigens

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    CLAUDIA STANCA

    2007-05-01

    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.

  7. Chimera states in a Hodgkin-Huxley model of thermally sensitive neurons

    Science.gov (United States)

    Glaze, Tera A.; Lewis, Scott; Bahar, Sonya

    2016-08-01

    Chimera states occur when identically coupled groups of nonlinear oscillators exhibit radically different dynamics, with one group exhibiting synchronized oscillations and the other desynchronized behavior. This dynamical phenomenon has recently been studied in computational models and demonstrated experimentally in mechanical, optical, and chemical systems. The theoretical basis of these states is currently under active investigation. Chimera behavior is of particular relevance in the context of neural synchronization, given the phenomenon of unihemispheric sleep and the recent observation of asymmetric sleep in human patients with sleep apnea. The similarity of neural chimera states to neural "bump" states, which have been suggested as a model for working memory and visual orientation tuning in the cortex, adds to their interest as objects of study. Chimera states have been demonstrated in the FitzHugh-Nagumo model of excitable cells and in the Hindmarsh-Rose neural model. Here, we demonstrate chimera states and chimera-like behaviors in a Hodgkin-Huxley-type model of thermally sensitive neurons both in a system with Abrams-Strogatz (mean field) coupling and in a system with Kuramoto (distance-dependent) coupling. We map the regions of parameter space for which chimera behavior occurs in each of the two coupling schemes.

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

    International Nuclear Information System (INIS)

    Obasaju, M.F.; Wiley, L.M.; Oudiz, D.J.; Raabe, O.; Overstreet, J.W.

    1989-01-01

    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)

  9. Diabetes mellitus induces bone marrow microangiopathy

    Science.gov (United States)

    Oikawa, Atsuhiko; Siragusa, Mauro; Quaini, Federico; Mangialardi, Giuseppe; Katare, Rajesh G.; Caporali, Andrea; van Buul, Jaap D.; van Alphen, Floris P.J.; Graiani, Gallia; Spinetti, Gaia; Kraenkel, Nicolle; Prezioso, Lucia; Emanueli, Costanza; Madeddu, Paolo

    2010-01-01

    Objective The impact of diabetes on the bone marrow (BM) microenvironment was not adequately explored. We investigated whether diabetes induces microvascular remodeling with negative consequence for BM homeostasis. Methods and results We found profound structural alterations in BM from type-1 diabetic mice, with depletion of the hematopoietic component and fatty degeneration. Blood flow (fluorescent microspheres) and microvascular density (immunohistochemistry) were remarkably reduced. Flow cytometry verified the depletion of MECA-32pos endothelial cells (ECs). Cultured ECs from BM of diabetic mice showed higher levels of oxidative stress, increased activity of the senescence marker β-galactosidase, reduced migratory and network-formation capacities and increased permeability and adhesiveness to BM mononuclear cells. Flow cytometry analysis of lineageneg c-Kitpos Sca-1pos (LSK) cell distribution along an in vivo Hoechst-33342 dye perfusion gradient documented that diabetes depletes LSK cells predominantly in the low-perfused part of the marrow. Cell depletion was associated to increased oxidative stress, DNA damage and activation of apoptosis. Boosting the anti-oxidative pentose phosphate pathway by benfotiamine supplementation prevented microangiopathy, hypoperfusion and LSK cell depletion. Conclusions We provide novel evidence for the presence of microangiopathy impinging on the integrity of diabetic BM. These discoveries offer the framework for mechanistic solutions of BM dysfunction in diabetes. PMID:20042708

  10. The Use of Endothelial Progenitor Cells for the Regeneration of Musculoskeletal and Neural Tissues

    OpenAIRE

    Kamei, Naosuke; Atesok, Kivanc; Ochi, Mitsuo

    2017-01-01

    Endothelial progenitor cells (EPCs) derived from bone marrow and blood can differentiate into endothelial cells and promote neovascularization. In addition, EPCs are a promising cell source for the repair of various types of vascularized tissues and have been used in animal experiments and clinical trials for tissue repair. In this review, we focused on the kinetics of endogenous EPCs during tissue repair and the application of EPCs or stem cell populations containing EPCs for tissue regenera...

  11. Marrow heterotopia in thalassemia

    Energy Technology Data Exchange (ETDEWEB)

    Papavasiliou, C.; Gouliamos, A.; Andreou, J.

    1986-05-01

    The subject of marrow heterotopia has been reviewed on the basis of 15 cases suffering from thalassemia. Other cases reported in the literature were also reviewed. Using conventional radiography, scintigraphy, computerized tomography and myelography, 17% of the cases admitted into the hospital with the diagnosis of Thalassemia, were found to have macroscopic masses of marrow heterotopia. The most common site of development of these masses was the costovertebral gutter, followed by the anterior end of the ribs and the extradural space of the spinal canal. In one case, masses were located in the maxillary antra. The clinical implications, the pathogenesis of the masses and the differential diagnosis from other tumour-like entities are discussed. Three patients presented with symptoms and signs of spinal cord compression. All three patients were treated satisfactorily with small doses of radiotherapy.

  12. Cytokinetic Analysis of Slowly Renewing Bone-Marrow Cells after Administration of Nitrogen Mustard

    Energy Technology Data Exchange (ETDEWEB)

    Haas, R.; Fliedner, T. M.; Stehle, H. [Abteilung fuer Klinische Physiologie der Universitaet Ulm, Ulm/Donau, Federal Republic of Germany (Germany)

    1968-08-15

    The continuous or repeated administration of tritiated thymidine into pregnant rats during organogenesis provides a method for the complete labelling of newborn rats. If these are continuously injected with tritiated thymidine for the first four weeks after birth, the fraction of labelled cells of all organs and cell-renewal systems is still 100% If completely labelled animals are sacrificed at regular intervals after the discontinuance of thymidine administration, one can distinguish two groups of cells with distinct differences in their cell renewal. While the reticular cells A and B, the endothelial cells and the bone-marrow lymphocytes belong to a slowly proliferating group of cells, the differentiated myelopoietic and erythropoietic cells of the bone marrow proliferate rapidly. That labelled erythropoietic or myelopoietic cells are not found later than 6-10 days after discontinuance of tritated thymidine injection in these animals argues strongly against the hypothesis that under normal steady-state conditions a G{sub 0} fraction exists in the bone-marrow, from which stem cells are deviated into the differentiated cell pools by adequate stimuli. The administration of nitrogen mustard in a dose sufficient to cause bone-marrow aplasia neither destroys nor stimulates the reticular cells and endothelial cells of the bone-marrow matrix. These cells retain their label and remain present in normal numbers throughout the period of observation after nitrogen mustard treatment: The only cell type in the marrow that changes its labelling intensity after nitrogen mustard administration is the marrow lymphocyte. The decrease in the fraction and intensity of labelled bone-marrow lymphocytes precedes the rapid regeneration of nitrogen mustard aplastic bone-marrow. This cell type, in our opinion, would be the only cell to qualify as a stem cell, although positive evidence is still lacking. (author)

  13. Chimera Type Behavior in Nonlocal Coupling System with Two Different Inherent Frequencies

    Science.gov (United States)

    Lin, Larry; Li, Ping-Cheng; Tseng, Hseng-Che

    2014-03-01

    From the research of Kuramoto and Strogatz, arrays of identical oscillators can display a remarkable pattern, named chimera state, in which phase-locked oscillators coexist with drifting ones in nonlocal coupling oscillator system. We consider further in this study, two groups of oscillators with different inherent frequencies and arrange them in a ring. When the difference of the inherent frequencies is within some specific parameter range, oscillators of nonlocal coupling system show two distinct chimera states. When the parameter value exceeds some threshold value, two chimera states disappear. They show different features. The statistical dynamic behavior of the system can be described by Kuramoto theory.

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

    DEFF Research Database (Denmark)

    Martens, Erik Andreas

    2010-01-01

    this 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....

  15. Robust Weak Chimeras in Oscillator Networks with Delayed Linear and Quadratic Interactions

    Science.gov (United States)

    Bick, Christian; Sebek, Michael; Kiss, István Z.

    2017-10-01

    We present an approach to generate chimera dynamics (localized frequency synchrony) in oscillator networks with two populations of (at least) two elements using a general method based on a delayed interaction with linear and quadratic terms. The coupling design yields robust chimeras through a phase-model-based design of the delay and the ratio of linear and quadratic components of the interactions. We demonstrate the method in the Brusselator model and experiments with electrochemical oscillators. The technique opens the way to directly bridge chimera dynamics in phase models and real-world oscillator networks.

  16. Chimera states in complex networks: interplay of fractal topology and delay

    Science.gov (United States)

    Sawicki, Jakub; Omelchenko, Iryna; Zakharova, Anna; Schöll, Eckehard

    2017-06-01

    Chimera states are an example of intriguing partial synchronization patterns emerging in networks of identical oscillators. They consist of spatially coexisting domains of coherent (synchronized) and incoherent (desynchronized) dynamics. We analyze chimera states in networks of Van der Pol oscillators with hierarchical connectivities, and elaborate the role of time delay introduced in the coupling term. In the parameter plane of coupling strength and delay time we find tongue-like regions of existence of chimera states alternating with regions of existence of coherent travelling waves. We demonstrate that by varying the time delay one can deliberately stabilize desired spatio-temporal patterns in the system.

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

    International Nuclear Information System (INIS)

    Adorini, L.; Gorini, G.; Covelli, V.; Ballardin, E.; di Michele, A.; Bassani, B.; Metalli, P.; Doria, G.

    1976-01-01

    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

  18. Mechanisms of appearance of amplitude and phase chimera states in ensembles of nonlocally coupled chaotic systems

    Science.gov (United States)

    Bogomolov, Sergey A.; Slepnev, Andrei V.; Strelkova, Galina I.; Schöll, Eckehard; Anishchenko, Vadim S.

    2017-02-01

    We explore the bifurcation transition from coherence to incoherence in ensembles of nonlocally coupled chaotic systems. It is firstly shown that two types of chimera states, namely, amplitude and phase, can be found in a network of coupled logistic maps, while only amplitude chimera states can be observed in a ring of continuous-time chaotic systems. We reveal a bifurcation mechanism by analyzing the evolution of space-time profiles and the coupling function with varying coupling coefficient and formulate the necessary and sufficient conditions for realizing the chimera states in the ensembles.

  19. The role of bone marrow-derived cells during the bone healing process in the GFP mouse bone marrow transplantation model.

    Science.gov (United States)

    Tsujigiwa, Hidetsugu; Hirata, Yasuhisa; Katase, Naoki; Buery, Rosario Rivera; Tamamura, Ryo; Ito, Satoshi; Takagi, Shin; Iida, Seiji; Nagatsuka, Hitoshi

    2013-03-01

    Bone healing is a complex and multistep process in which the origin of the cells participating in bone repair is still unknown. The involvement of bone marrow-derived cells in tissue repair has been the subject of recent studies. In the present study, bone marrow-derived cells in bone healing were traced using the GFP bone marrow transplantation model. Bone marrow cells from C57BL/6-Tg (CAG-EGFP) were transplanted into C57BL/6 J wild mice. After transplantation, bone injury was created using a 1.0-mm drill. Bone healing was histologically assessed at 3, 7, 14, and 28 postoperative days. Immunohistochemistry for GFP; double-fluorescent immunohistochemistry for GFP-F4/80, GFP-CD34, and GFP-osteocalcin; and double-staining for GFP and tartrate-resistant acid phosphatase were performed. Bone marrow transplantation successfully replaced the hematopoietic cells into GFP-positive donor cells. Immunohistochemical analyses revealed that osteoblasts or osteocytes in the repair stage were GFP-negative, whereas osteoclasts in the repair and remodeling stages and hematopoietic cells were GFP-positive. The results indicated that bone marrow-derived cells might not differentiate into osteoblasts. The role of bone marrow-derived cells might be limited to adjustment of the microenvironment by differentiating into inflammatory cells, osteoclasts, or endothelial cells in immature blood vessels.

  20. The acute exposure effects of inhaled nickel nanoparticles on murine endothelial progenitor cells.

    Science.gov (United States)

    Liberda, Eric N; Cuevas, Azita K; Qu, Qingshan; Chen, Lung Chi

    2014-08-01

    The discovery of endothelial progenitor cells (EPCs) may help to explain observed cardiovascular effects associated with inhaled nickel nanoparticle exposures, such as increases in vascular inflammation, generation of reactive oxygen species, altered vasomotor tone and potentiated atherosclerosis in murine species. Following an acute whole body inhalation exposure to 500 µg/m(3) of nickel nanoparticles for 5 h, bone marrow EPCs from C57BL/6 mice were isolated. EPCs were harvested for their RNA or used in a variety of assays including chemotaxis, tube formation and proliferation. Gene expression was assessed for important receptors involved in EPC mobilization and homing using RT-PCR methods. EPCs, circulating endothelial progenitor cells (CEPCs), circulating endothelial cells (CECs) and endothelial microparticles (EMPs) were quantified on a BD FACSCalibur to examine endothelial damage and repair associated with the exposure. Acute exposure to inhaled nickel nanoparticles significantly increased both bone marrow EPCs as well as their levels in circulation (CEPCs). CECs were significantly elevated indicating that endothelial damage occurred due to the exposure. There was no significant difference in EMPs between the two groups. Tube formation and chemotaxis, but not proliferation, of bone marrow EPCs was impaired in the nickel nanoparticle exposed group. These results coincided with a decrease in the mRNA of receptors involved in EPC mobilization and homing. These data provide new insight into how an acute nickel nanoparticle exposure to half of the current Occupational Safety & Health Administration (OSHA) permissible exposure limit may adversely affect EPCs and exacerbate cardiovascular disease states.

  1. Construction and characterization of the interdomain chimeras using Cry11Aa and Cry11Ba from Bacillus thuringiensis and identification of a possible novel toxic chimera.

    Science.gov (United States)

    Sun, Yunjun; Zhao, Qiang; Zheng, Dasheng; Ding, Xuezhi; Wang, Jingfang; Hu, Quanfang; Yuan, Zhiming; Park, Hyun-Woo; Xia, Liqiu

    2014-01-01

    Three structural domains of mosquitocidal Cry11Aa and Cry11Ba from Bacillus thuringiensis were exchanged to produce interdomain chimeras [BAA (11Ba/11Aa/11Aa), ABA (11Aa/11Ba/11Aa), AAB (11Aa/11Aa/11Ba), ABB (11Aa/11Ba/11Ba), BAB (11Ba/11Aa/11Ba), BBA (11Ba/11Ba/11Aa]. Chimeras BAB, BAA, BBA, and AAB formed inclusion bodies in the crystal-negative B. thuringiensis host and produced expected protein bands on SDS-PAGE gel. However, no inclusion body or target protein could be found for chimeras ABA and ABB. In bioassays using the fourth-instar larvae of Culex quinquefasciatus and Aedes aegypti, AAB had ~50 % lethal concentrations of 4.8 and 2.2 μg ml(-1), respectively; however, the rest of chimeras were not toxic. This study thus helps to understand the domain-function relationships of the Cry11Aa and Cry11Ba toxins. The toxic chimera, AAB, might be a candidate for mosquito control as its amino acid sequence is different from the two parental toxins.

  2. On applications of chimera grid schemes to store separation

    Science.gov (United States)

    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.

  3. Amplitude mediated chimera states with active and inactive oscillators

    Science.gov (United States)

    Mukherjee, Rupak; Sen, Abhijit

    2018-05-01

    The emergence and nature of amplitude mediated chimera states, spatio-temporal patterns of co-existing coherent and incoherent regions, are investigated for a globally coupled system of active and inactive Ginzburg-Landau oscillators. The existence domain of such states is found to shrink and shift in parametric space with the increase in the fraction of inactive oscillators. The role of inactive oscillators is found to be twofold—they get activated to form a separate region of coherent oscillations and, in addition, decrease the common collective frequency of the coherent regions by their presence. The dynamical origin of these effects is delineated through a bifurcation analysis of a reduced model system that is based on a mean field approximation. Our results may have practical implications for the robustness of such states in biological or physical systems where age related deterioration in the functionality of components can occur.

  4. Present status of the Chimera-Isospin experiment

    International Nuclear Information System (INIS)

    Politi, G.; Arena, N.; Cardella, G.; DeFilippo, E.; Lanzano, G.; Nigro, S.L.; Pagano, A.; Papa, M.; Pirrone, S.; Russotto, P.; Alderighi, M.; Sechi, G.; Sperduto, M.L.; Amorini, F.; Anzalone, A.; Baran, V.; Bonasera, A.; Cavallaro, S.L.; Colonna, M.; Di Toro, M.; LaGuidara, E.; Lanzalone, G.; IaconoManno, M.; Giustolisi, F.; Maiolino, C.; Porto, F.; Rizzo, F.; Trifiro, A.; Trimarchi, M.; Auditore, L.; Barna, R.; DePasquale, D.; Berceanu, I.; Petrovici, M.; Pop, A.; Blicharska, J.; Grzeszczuk, A.; Kowalski, S.; Zipper, W.; Borderie, B.; LeNeindre, N.; Rivet, M.F.; Bougault, R.; Briczycnski, J.; Gawlikowicz, W.; Majka, Z.; Planeta, R.; Bruno, M.; D'Agostino, M.; Fuschini, E.; Geraci, E.; Vannini, G.; Chatterjee, M.B.; Chbihi, A.; Wieleczko, J.P.; Cibor, J.; Dayras, R.; Guazzoni, P.; Russo, S.; Sassi, M.; Zetta, L.; Guinet, D.; Li, S.; Wu, H.; Xiao, Z.; Nicolis, N.G.; Piasecki, E.; Swiderski, L.; Rosato, E.; Vigilante, M.; Wilczynski, J.; Siwek-Wilczynska, K.; Skwira, I.

    2003-01-01

    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)

  5. In vitro neoformation of grape chimeras (Vitis vinifera L.

    Directory of Open Access Journals (Sweden)

    Sandrine Verdisson

    1999-03-01

    Full Text Available Difference in grape sensitivity to Botrytis cinerea attacks between cultivars was explained by differences in the epidermic tissue of the fruit. Therefore, this work was conducted to create a grape periclinal chimera, whose fruits would combine the skin of a Botrytis tolerant cultivar with a pulp of an another cultivar admitted its good organoleptic quality and productivity. In a first time, graftings of two cultivars (Chardonnay and Pinot noir were conducted in vitro on 5 different media supplemented with various plant growth regulators. Adventitious shoots were only observed on medium containing BAP and GA3 from a mixed callus structure after four weeks of darkness followed by a light/dark regime. In a second time, RAPD analysis, conducted on these plants, showed their chimerical characteristics.

  6. Synthesis of Alkyl-Glycerolipids Standards for Gas Chromatography Analysis: Application for Chimera and Shark Liver Oils

    Science.gov (United States)

    Pinault, Michelle; Guimaraes, Cyrille; Couthon, Hélène; Thibonnet, Jérôme; Fontaine, Delphine; Chantôme, Aurélie; Chevalier, Stephan; Jaffrès, Paul-Alain; Vandier, Christophe

    2018-01-01

    Natural O-alkyl-glycerolipids, also known as alkyl-ether-lipids (AEL), feature a long fatty alkyl chain linked to the glycerol unit by an ether bond. AEL are ubiquitously found in different tissues but, are abundant in shark liver oil, breast milk, red blood cells, blood plasma, and bone marrow. Only a few AEL are commercially available, while many others with saturated or mono-unsaturated alkyl chains of variable length are not available. These compounds are, however, necessary as standards for analytical methods. Here, we investigated different reported procedures and we adapted some of them to prepare a series of 1-O-alkyl-glycerols featuring mainly saturated alkyl chains of various lengths (14:0, 16:0, 17:0, 19:0, 20:0, 22:0) and two monounsaturated chains (16:1, 18:1). All of these standards were fully characterized by NMR and GC-MS. Finally, we used these standards to identify the AEL subtypes in shark and chimera liver oils. The distribution of the identified AEL were: 14:0 (20–24%), 16:0 (42–54%) and 18:1 (6–16%) and, to a lesser extent, (0.2–2%) for each of the following: 16:1, 17:0, 18:0, and 20:0. These standards open the possibilities to identify AEL subtypes in tumours and compare their composition to those of non-tumour tissues. PMID:29570630

  7. Bovine and human lactoferricin peptides: chimeras and new cyclic analogs.

    Science.gov (United States)

    Arias, Mauricio; McDonald, Lindsey J; Haney, Evan F; Nazmi, Kamran; Bolscher, Jan G M; Vogel, Hans J

    2014-10-01

    Lactoferrin (LF) is an important antimicrobial and immune regulatory protein present in neutrophils and most exocrine secretions of mammals. The antimicrobial activity of LF has been related to the presence of an antimicrobial peptide sequence, called lactoferricin (LFcin), located in the N-terminal region of the protein. The antimicrobial activity of bovine LFcin is considerably stronger than the human version. In this work, chimera peptides combining segments of bovine and human LFcin were generated in order to study their antimicrobial activity and mechanism of action. In addition, the relevance of the conserved disulfide bridge and the resulting cyclic structure of both LFcins were analyzed by using "click chemistry" and sortase A-catalyzed cyclization of the peptides. The N-terminal region of bovine LFcin (residues 17-25 of bovine LF) proved to be very important for the antimicrobial activity of the chimera peptides against E. coli, when combined with the C-terminal region of human LFcin. Similarly the cyclic bovine LFcin analogs generated by "click chemistry" and sortase A preserved the antimicrobial activity of the original peptide, showing the significance of these two techniques in the design of cyclic antimicrobial peptides. The mechanism of action of bovine LFcin and its active derived peptides was strongly correlated with membrane leakage in E. coli and up to some extent with the ability to induce vesicle aggregation. This mechanism was also preserved under conditions of high ionic strength (150 mM NaCl) illustrating the importance of these peptides in a more physiologically relevant system.

  8. Association of immunity and tolerance of host H-2 determinants in irradiated F1 hybrid mice reconstituted with bone marrow cells from one parental strain

    International Nuclear Information System (INIS)

    Sprent, J.; von Boehmer, H.; Nabholz, M.

    1975-01-01

    Semiallogeneic radiation chimeras were prepared by injecting heavily irradiated F 1 hybrid mice with bone marrow cells from one parental strain; the bone marrow cells were treated with anti-theta serum and complement to remove T cells and injected in large numbers (2 x 10 7 cells). The mice survived in excellent health until sacrifice 6 mo later. Thoracic duct cannulation at this stage showed that the mice possessed normal numbers of recirculating lymphocytes. Close to 100 percent of thoracic duct lymphocytes and lymph node cells were shown to be of donor strain origin. The capacity of lymphocytes from the chimeras to respond to host-type determinants was tested in mixed leukocyte culture and in an assay for cell-mediated lympholysis (CML). Mixed leukocyte reactions (MLR) were measured both in vitro and in vivo; tumor cells and phytohemagglutinin-stimulated blast cells were used as target cells for measuring CML. While responding normally to third party determinants, cells from the chimeras gave a definite, though reduced MLR when exposed to host-type determinants. However, this proliferative response to host-type determinants, unlike that to third party determinants, was not associated with differentiation into cytotoxic lymphocytes

  9. Integration of the GET electronics for the CHIMERA and FARCOS devices

    Science.gov (United States)

    De Filippo, E.; Acosta, L.; Auditore, L.; Boiano, C.; Cardella, G.; Castoldi, A.; D’Andrea, M.; De Luca, S.; Favela, F.; Fichera, F.; Giudice, N.; Gnoffo, B.; Grimaldi, A.; Guazzoni, C.; Lanzalone, G.; Librizzi, F.; Litrico, P.; Maiolino, C.; Maffesanti, S.; Martorana, NS; Pagano, A.; Pagano, EV; Papa, M.; Parsani, T.; Passaro, G.; Pirrone, S.; Politi, G.; Previdi, F.; Quattrocchi, L.; Rizzo, F.; Russotto, P.; Saccà, G.; Salemi, G.; Sciliberto, D.; Trifirò, A.; Trimarchi, M.

    2018-05-01

    A new front-end based on digital GET electronics has been adopted for the readout of the CsI(Tl) detectors of the CHIMERA 4π multi-detector and for the new modular Femtoscopy Array for Correlation and Spectroscopy (FARCOS). It is expected that the coupling of CHIMERA with the FARCOS array, featuring high angular and energy resolution, and the adoption of the new digital electronics will be well suited for improving specific future data analysis, with the full shape storage of the signals, in the field of heavy ion reactions with stable and exotic beams around the Fermi energies domain. Integration of the GET electronics with CHIMERA and FARCOS devices and with the local analog data acquisition will be briefly discussed. We present some results from previous experimental tests and from the first in-beam experiment (Hoyle-Gamma) with the coupled GET+CHIMERA data acquisition.

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

    Science.gov (United States)

    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.

  11. Chimera states in two-dimensional networks of locally coupled oscillators

    Science.gov (United States)

    Kundu, Srilena; Majhi, Soumen; Bera, Bidesh K.; Ghosh, Dibakar; Lakshmanan, M.

    2018-02-01

    Chimera state is defined as a mixed type of collective state in which synchronized and desynchronized subpopulations of a network of coupled oscillators coexist and the appearance of such anomalous behavior has strong connection to diverse neuronal developments. Most of the previous studies on chimera states are not extensively done in two-dimensional ensembles of coupled oscillators by taking neuronal systems with nonlinear coupling function into account while such ensembles of oscillators are more realistic from a neurobiological point of view. In this paper, we report the emergence and existence of chimera states by considering locally coupled two-dimensional networks of identical oscillators where each node is interacting through nonlinear coupling function. This is in contrast with the existence of chimera states in two-dimensional nonlocally coupled oscillators with rectangular kernel in the coupling function. We find that the presence of nonlinearity in the coupling function plays a key role to produce chimera states in two-dimensional locally coupled oscillators. We analytically verify explicitly in the case of a network of coupled Stuart-Landau oscillators in two dimensions that the obtained results using Ott-Antonsen approach and our analytical finding very well matches with the numerical results. Next, we consider another type of important nonlinear coupling function which exists in neuronal systems, namely chemical synaptic function, through which the nearest-neighbor (locally coupled) neurons interact with each other. It is shown that such synaptic interacting function promotes the emergence of chimera states in two-dimensional lattices of locally coupled neuronal oscillators. In numerical simulations, we consider two paradigmatic neuronal oscillators, namely Hindmarsh-Rose neuron model and Rulkov map for each node which exhibit bursting dynamics. By associating various spatiotemporal behaviors and snapshots at particular times, we study the chimera

  12. Chimera states in an ensemble of linearly locally coupled bistable oscillators

    Science.gov (United States)

    Shchapin, D. S.; Dmitrichev, A. S.; Nekorkin, V. I.

    2017-11-01

    Chimera states in a system with linear local connections have been studied. The system is a ring ensemble of analog bistable self-excited oscillators with a resistive coupling. It has been shown that the existence of chimera states is not due to the nonidentity of oscillators and noise, which is always present in real experiments, but is due to the nonlinear dynamics of the system on invariant tori with various dimensions.

  13. Temporal intermittency and the lifetime of chimera states in ensembles of nonlocally coupled chaotic oscillators

    Science.gov (United States)

    Semenova, N. I.; Strelkova, G. I.; Anishchenko, V. S.; Zakharova, A.

    2017-06-01

    We describe numerical results for the dynamics of networks of nonlocally coupled chaotic maps. Switchings in time between amplitude and phase chimera states have been first established and studied. It has been shown that in autonomous ensembles, a nonstationary regime of switchings has a finite lifetime and represents a transient process towards a stationary regime of phase chimera. The lifetime of the nonstationary switching regime can be increased to infinity by applying short-term noise perturbations.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  15. Inhibition of Apoptosis Overcomes Stage-Related Compatibility Barriers to Chimera Formation in Mouse Embryos.

    Science.gov (United States)

    Masaki, Hideki; Kato-Itoh, Megumi; Takahashi, Yusuke; Umino, Ayumi; Sato, Hideyuki; Ito, Keiichi; Yanagida, Ayaka; Nishimura, Toshinobu; Yamaguchi, Tomoyuki; Hirabayashi, Masumi; Era, Takumi; Loh, Kyle M; Wu, Sean M; Weissman, Irving L; Nakauchi, Hiromitsu

    2016-11-03

    Cell types more advanced in development than embryonic stem cells, such as EpiSCs, fail to contribute to chimeras when injected into pre-implantation-stage blastocysts, apparently because the injected cells undergo apoptosis. Here we show that transient promotion of cell survival through expression of the anti-apoptotic gene BCL2 enables EpiSCs and Sox17 + endoderm progenitors to integrate into blastocysts and contribute to chimeric embryos. Upon injection into blastocyst, BCL2-expressing EpiSCs contributed to all bodily tissues in chimeric animals while Sox17 + endoderm progenitors specifically contributed in a region-specific fashion to endodermal tissues. In addition, BCL2 expression enabled rat EpiSCs to contribute to mouse embryonic chimeras, thereby forming interspecies chimeras that could survive to adulthood. Our system therefore provides a method to overcome cellular compatibility issues that typically restrict chimera formation. Application of this type of approach could broaden the use of embryonic chimeras, including region-specific chimeras, for basic developmental biology research and regenerative medicine. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Spiral wave chimera states in large populations of coupled chemical oscillators

    Science.gov (United States)

    Totz, Jan Frederik; Rode, Julian; Tinsley, Mark R.; Showalter, Kenneth; Engel, Harald

    2018-03-01

    The coexistence of coherent and incoherent dynamics in a population of identically coupled oscillators is known as a chimera state1,2. Discovered in 20023, this counterintuitive dynamical behaviour has inspired extensive theoretical and experimental activity4-15. The spiral wave chimera is a particularly remarkable chimera state, in which an ordered spiral wave rotates around a core consisting of asynchronous oscillators. Spiral wave chimeras were theoretically predicted in 200416 and numerically studied in a variety of systems17-23. Here, we report their experimental verification using large populations of nonlocally coupled Belousov-Zhabotinsky chemical oscillators10,18 in a two-dimensional array. We characterize previously unreported spatiotemporal dynamics, including erratic motion of the asynchronous spiral core, growth and splitting of the cores, as well as the transition from the chimera state to disordered behaviour. Spiral wave chimeras are likely to occur in other systems with long-range interactions, such as cortical tissues24, cilia carpets25, SQUID metamaterials26 and arrays of optomechanical oscillators9.

  17. Starvation marrow – gelatinous transformation of bone marrow

    Directory of Open Access Journals (Sweden)

    Eric Osgood

    2014-09-01

    Full Text Available Gelatinous bone marrow transformation (GMT, also known as starvation marrow, represents a rare pathological entity of unclear etiology, in which bone marrow histopathology demonstrates hypoplasia, fat atrophy, and gelatinous infiltration. The finding of gelatinous marrow transformation lacks disease specificity; rather, it is an indicator of severe illness and a marker of poor nutritional status, found in patients with eating disorders, acute febrile illnesses, acquired immunodeficiency syndrome, alcoholism, malignancies, and congestive heart failure. We present a middle-aged woman with a history of alcoholism, depression, and anorexia nervosa who presented with failure to thrive and macrocytic anemia, with bone marrow examination demonstrative of gelatinous transformation, all of which resolved with appropriate treatment. To our knowledge, there are very few cases of GMT which have been successfully treated; thus, our case highlights the importance of proper supportive management.

  18. Expression of T cell antigen receptor genes in the thymus of irradiated mice after bone marrow transplantation

    International Nuclear Information System (INIS)

    Matsuzaki, G.; Yoshikai, Y.; Kishihara, K.; Nomoto, K.

    1988-01-01

    Sequential appearance of the expression of T cell antigen receptor genes was investigated in the thymus of irradiated mice at the early stage after transplantation of Thy-1 congeneic H-2 compatible allogeneic bone marrow cells. The first cells to repopulate the thymus on day 7 after bone marrow transplantation were intrathymic radioresistant T cell precursors, which expanded mainly to CD4+CD8+ host-type thymocytes by day 14. A high level of gamma gene expression but a much reduced level of alpha and beta gene expression were detected in the host-type thymocytes on day 7. During regeneration of these cells, gamma-chain messages fell to low level and alpha and beta mRNA levels increased. The thymus of the recipients began to be repopulated by donor-derived T cells about 2 wk after bone marrow transplantation and was almost completely replaced by the third week. An ordered expression of gamma then beta and alpha-chain gene transcript was also observed in the donor-type thymocytes at the early stage after bone marrow transplantation. The use of thymocytes at early stage in whole-body irradiated bone marrow chimera provides a pertinent source for investigating the molecular mechanism of T cell differentiation in adult thymus

  19. Bone marrow edema syndrome

    International Nuclear Information System (INIS)

    Korompilias, Anastasios V.; Lykissas, Marios G.; Beris, Alexandros E.; Karantanas, Apostolos H.

    2009-01-01

    Bone marrow edema syndrome (BMES) refers to transient clinical conditions with unknown pathogenic mechanism, such as transient osteoporosis of the hip (TOH), regional migratory osteoporosis (RMO), and reflex sympathetic dystrophy (RSD). BMES is primarily characterized by bone marrow edema (BME) pattern. The disease mainly affects the hip, the knee, and the ankle of middle-aged males. Many hypotheses have been proposed to explain the pathogenesis of the disease. Unfortunately, the etiology of BMES remains obscure. The hallmark that separates BMES from other conditions presented with BME pattern is its self-limited nature. Laboratory tests usually do not contribute to the diagnosis. Histological examination of the lesion is unnecessary. Plain radiographs may reveal regional osseous demineralization. Magnetic resonance imaging is mainly used for the early diagnosis and monitoring the progression of the disease. Early differentiation from other aggressive conditions with long-term sequelae is essential in order to avoid unnecessary treatment. Clinical entities, such as TOH, RMO, and RSD are spontaneously resolving, and surgical treatment is not needed. On the other hand, early differential diagnosis and surgical treatment in case of osteonecrosis is of crucial importance. (orig.)

  20. Genetic control of eosinophilia in mice: gene(s) expressed in bone marrow-derived cells control high responsiveness

    International Nuclear Information System (INIS)

    Vadas, M.A.

    1982-01-01

    A heterogeneity in the capacity of strains of mice to mount eosinophilia is described. BALB/c and C3H are eosinophil high responder strains (EO-HR) and CBA and A/J are eosinophil low responder strains (EO-LR), judged by the response of blood eosinophils to Ascaris suum, and the response of blood, bone marrow, and spleen eosinophils to keyhole limpet hemocyanin given 2 days after 150 mg/kg cyclophosphamide. Some of the gene(s) for high responsiveness appear to be dominant because (EO-HR x EO-LR)F 1 mice were intermediate to high responders. This gene is expressed in bone marrow-derived cells because radiation chimeras of the type EO-HR→F 1 were high responders and EO-LR→F 1 were low responders. This description of a genetic control of eosinophilia in mice may be useful in understanding the role of this cell in parasite immunity and allergy

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    . Despite relatively conservative substitutions, the lipid-facing chimeras (TM1, TM2, TM4, TM5, TM6 or TM7) were retained in the endoplasmic reticulum/cis-Golgi network. With the exception of the TM7 chimera that did not bind ligand, the lipid-facing chimeras bound ligand with low affinity, but similar...... oligomerization studies demonstrated energy transfer between the wild-type complement factor 5a receptor and the lipid-facing chimeras, suggesting that the lipid-facing residues within a single TM segment are not essential for oligomerization. These studies highlight the importance of the lipid-facing residues...

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

    International Nuclear Information System (INIS)

    Zhu Yun; Zheng Zhi-Gang; Yang Jun-Zhong

    2013-01-01

    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)

  3. Effects and Complications of Bone-Marrow Transplantation in Man

    Energy Technology Data Exchange (ETDEWEB)

    Mathe, G.; Schwarzenberg, L.; Miel, J.L. A; Schneider, M.; Cattan, A.; Schlumberger, J. R. [Institut de cancerologie et immunogenetique, Hopital Paul Brousse, Villejuif (France)

    1969-07-15

    Full text: Allogenic bone-marrow grafting in 24 human leukaemic subjects is described. The graft failed in 7 cases and took in 17 cases. In the latter group, all 17 cases were complicated by the secondary syndrome which was-fatal in 13 cases and controlled in 4 cases. The immunogenetic and immunological factors determining the establishment and evolution of haematological radiochimeras in man are discussed. The choice of donor is fundamental. Three tests are effective in donor selection, the indirect histocompatibility test, the leucocyte antigen test and the reaction of donor and recipient leucocytes in the dermis of an irradiated hamster. When marrow from several donors is transfused, the recipient spontaneously selects the genetically nearest. It seems likely there is more chance of finding a suitable donor among genetically related subjects than among those who are unrelated. The frequency of graft take seems slightly lower in recipients who have previously received blood transfusions. Total bone-marrow graft is associated with specific tolerance towards donor tissues. This is paralleled by the production in the chimera of immunoglobulins produced by the graft. The secondary syndrome seems, as in animals, to be related essentially to the graft-versus-host reaction. It is convenient to distinguish among its various manifestations, on the one hand, those lesions which are readily controlled such as hepatitis or erythrodermia associated with infiltration and proliferation of immunologically competent cells from the graft and, on the other hand, immune insufficiency with regard to micro-organisms, especially viruses and Candida albicans. This latter group, the mechanism of which is complex, still eludes attempts at preventive and curative control. The use of multiple donors and the administration of cortisone during marrow transfusion and A-methopterin and/or cyclophosphamide in the days following transfusions; seem to have reduced the severity of the secondary

  4. Artificial muscle: the human chimera is the future.

    Science.gov (United States)

    Tozzi, P

    2011-12-14

    Severe heart failure and cerebral stroke are broadly associated with the impairment of muscular function that conventional treatments struggle to restore. New technologies enable the construction of "smart" materials that could be of great help in treating diseases where the main problem is muscle weakness. These materials "behave" similarly to biological systems, because the material directly converts energy, for example electrical energy into movement. The extension and contraction occur silently like in natural muscles. The real challenge is to transfer this amazing technology into devices that restore or replace the mechanical function of failing muscle. Cardiac assist devices based on artificial muscle technology could envelope a weak heart and temporarily improve its systolic function, or, if placed on top of the atrium, restore the atrial kick in chronic atrial fibrillation. Artificial sphincters could be used to treat urinary incontinence after prostatectomy or faecal incontinence associated with stomas. Artificial muscles can restore the ability of patients with facial paralysis due to stroke or nerve injury to blink. Smart materials could be used to construct an artificial oesophagus including peristaltic movement and lower oesophageal sphincter function to replace the diseased oesophagus thereby avoiding the need for laparotomy to mobilise stomach or intestine. In conclusion, in the near future, smart devices will integrate with the human body to fill functional gaps due to organ failure, and so create a human chimera.

  5. Present status of the Chimera-Isospin experiment

    Energy Technology Data Exchange (ETDEWEB)

    Politi, G.; Arena, N.; Cardella, G.; DeFilippo, E.; Lanzano, G.; Nigro, S.L.; Pagano, A.; Papa, M.; Pirrone, S.; Russotto, P. [Catania Univ., INFN (Italy); Alderighi, M.; Sechi, G.; Sperduto, M.L. [Milano Univ., INFN, CNR (Italy); Amorini, F.; Anzalone, A.; Baran, V.; Bonasera, A.; Cavallaro, S.L.; Colonna, M.; Di Toro, M.; LaGuidara, E.; Lanzalone, G.; IaconoManno, M.; Giustolisi, F.; Maiolino, C.; Porto, F.; Rizzo, F.; Trifiro, A.; Trimarchi, M. [Catania Univ., INFN, Lab. Nazionali del Sud (Italy); Auditore, L.; Barna, R.; DePasquale, D. [Messina Univ., INFN (Italy); Berceanu, I.; Petrovici, M.; Pop, A. [Inst. for Physics and Nuclear Engineering, Bucharest (Romania); Blicharska, J.; Grzeszczuk, A.; Kowalski, S.; Zipper, W. [Univ. of Silesia, Inst. of Physics, Katowice (Poland); Borderie, B.; LeNeindre, N.; Rivet, M.F. [Paris-11 Univ., IPN-IN2P3-CNRS, 91 - Orsay (France); Bougault, R. [Caen Univ., LPC-ISMRA (France); Briczycnski, J.; Gawlikowicz, W.; Majka, Z.; Planeta, R. [M. Smoluchowski Inst. of Physics, Jagellonian Univ., Cracow (Poland); Bruno, M.; D' Agostino, M.; Fuschini, E.; Geraci, E.; Vannini, G. [Bologna Univ., INFN (Italy); Chatterjee, M.B. [Saha Inst. of Nuclear Physics, NIS Div., Kolkata (India); Chbihi, A.; Wieleczko, J.P. [GANIL -CEA-IN2P3-CNRS, 14 - Caen (France); Cibor, J. [H.Niewodniczanski Inst. of Nuclear Physics, Cracow (Poland); Dayras, R. [CEA Saclay, Dept. d' Astrophysique, de Physique des Particules, de Physique Nucleaire et de l' Instrumentation Associee, SPhN, 91- Gif sur Yvette (France); Guazzoni, P.; Russo, S.; Sassi, M.; Zetta, L. [Milano Univ., INFN (Italy); Guinet, D. [Univ. Claude Bernard, IPN-IN2P3-CNRS, 69 - Lyon (France); Li, S.; Wu, H.; Xiao, Z. [Inst. of Modern Physics, Lanzhou (China); Nicolis, N.G. [Ioannina Univ., Dept. of Physics (Greece); Piasecki, E.; Swiderski, L.; Siwek-Wilczynska, K.; Skwira, I. [Warsaw Univ., Inst. for Experimental Physics (Poland); Rosato, E.; Vigilante, M.; Wilczynski, J.

    2003-07-01

    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 4{pi} geometry. The experimental results have confirmed the capability of the apparatus for good isotopic identification of light charged particles and light fragments (3

  6. Multidimensional simulations of core-collapse supernovae with CHIMERA

    Science.gov (United States)

    Lentz, Eric J.; Bruenn, S. W.; Yakunin, K.; Endeve, E.; Blondin, J. M.; Harris, J. A.; Hix, W. R.; Marronetti, P.; Messer, O. B.; Mezzacappa, A.

    2014-01-01

    Core-collapse supernovae are driven by a multidimensional neutrino radiation hydrodynamic (RHD) engine, and full simulation requires at least axisymmetric (2D) and ultimately symmetry-free 3D RHD simulation. We present recent and ongoing work with our multidimensional RHD supernova code CHIMERA to understand the nature of the core-collapse explosion mechanism and its consequences. Recently completed simulations of 12-25 solar mass progenitors(Woosley & Heger 2007) in well resolved (0.7 degrees in latitude) 2D simulations exhibit robust explosions meeting the observationally expected explosion energy. We examine the role of hydrodynamic instabilities (standing accretion shock instability, neutrino driven convection, etc.) on the explosion dynamics and the development of the explosion energy. Ongoing 3D and 2D simulations examine the role that simulation resolution and the removal of the imposed axisymmetry have in the triggering and development of an explosion from stellar core collapse. Companion posters will explore the gravitational wave signals (Yakunin et al.) and nucleosynthesis (Harris et al.) of our simulations.

  7. [Circulating endothelial cells: biomarkers for monitoring activity of antiangiogenic therapy].

    Science.gov (United States)

    Farace, Françoise; Bidart, Jean-Michel

    2007-07-01

    Tumor vessel formation is largely dependent on the recruitment of endothelial cells. Rare in healthy individuals, circulating endothelial cells (CEC) are shed from vessel walls and enter the circulation reflecting endothelial damage or dysfunction. Increased numbers of CEC have been documented in different types of cancer. Recent studies have suggested the role for CEC in tumor angiogenesis, but whose presence could also reflect normal endothelium perturbation in cancer. Originating from the bone marrow rather than from vessel walls, endothelial progenitor cells (EPC) are mobilized following tissue ischemia and may be recruited to complement local angiogenesis supplied by existing endothelium. Recently, studies in mouse models suggest that the circulating fraction of endothelial progenitors (CEP) is involved in tumor angiogenesis but their contribution is less clear in humans. The detection of CEC and CEP is difficult and impeded by the rarity of these cells. They may have important clinical implication as novel biomarkers susceptible to predict more efficiently and rapidly the therapeutic response to anti-angiogenic treatments. However, a methodological consensus would be necessary in order to correctly evaluate the clinical interest of CEC and CEP in patients.

  8. β3-Adrenergic Regulation of EPC Features Through Manipulation of the Bone Marrow MSC Niche.

    Science.gov (United States)

    Vafaei, Rana; Nassiri, Seyed Mahdi; Siavashi, Vahid

    2017-12-01

    Mesenchymal stem cells (MSCs) reside in a specific niche in the bone marrow, however, biological features of this niche are still not fully understood. Given the interactions of MSCs with endothelial cells in different tissues, bone marrow MSC niche may influence the biological features of endothelial progenitor cells (EPCs). To understand the role of the sympathetic nervous system in regulation of the MSC niche, we examined whether the manipulation of the MSC niche via β3-adrenergic signals will affect EPC features. A selective β3 agonist (BRL37344) or a β3 antagonist (SR59230A) was administered in mice for 2 weeks to determine the potential effects of these regimens on the population of CD133 + stem cells in the bone marrow. Then, bone marrow-derived MSCs and EPCs were harvested and expanded from the mice to examine the effect of changes in the MSC niche on EPC features. Improved MSC colony forming potency with increased bone marrow stromal cell-derived factor 1 (SDF-1) (also known as C-X-C motif chemokine 12 [CXCL12]) expression was shown as a result of intensification of the bone marrow adrenergic signals through BRL37344 injection. On the other hand, the blockage of these signals limited the expression level of SDF-1 and resulted in bone marrow enrichment of CD133 + cells. Manipulation of the MSC niche and decreased SDF-1 expression via SR59230A injection also prompted EPCs to form more colonies with augmented proliferation and differentiation capacity. Overall, our results indicate that the β3-adrenergic signals regulate the MSC niche, thereby resulting in modulation of EPC biological features. J. Cell. Biochem. 118: 4753-4761, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  9. Data on bone marrow stem cells delivery using porous polymer scaffold

    Directory of Open Access Journals (Sweden)

    Ramasatyaveni Geesala

    2016-03-01

    Full Text Available Low bioavailability and/or survival at the injury site of transplanted stem cells necessitate its delivery using a biocompatible, biodegradable cell delivery vehicle. In this dataset, we report the application of a porous biocompatible, biodegradable polymer network that successfully delivers bone marrow stem cells (BMSCs at the wound site of a murine excisional splint wound model. In this data article, we are providing the additional data of the reference article “Porous polymer scaffold for on-site delivery of stem cells – protects from oxidative stress and potentiates wound tissue repair” (Ramasatyaveni et al., 2016 [1]. This data consists of the characterization of bone marrow stem cells (BMSCs showing the pluripotency and stem cell-specific surface markers. Image analysis of the cellular penetration into PEG–PU polymer network and the mechanism via enzymatic activation of MMP-2 and MMP-13 are reported. In addition, we provide a comparison of various routes of transplantation-mediated BMSCs engraftment in the murine model using bone marrow transplantation chimeras. Furthermore, we included in this dataset the engraftment of BMSCs expressing Sca-1+Lin−CD133+CD90.2+ in post-surgery day 10.

  10. Generation of an adenovirus-parvovirus chimera with enhanced oncolytic potential.

    Science.gov (United States)

    El-Andaloussi, Nazim; Bonifati, Serena; Kaufmann, Johanna K; Mailly, Laurent; Daeffler, Laurent; Deryckère, François; Nettelbeck, Dirk M; Rommelaere, Jean; Marchini, Antonio

    2012-10-01

    In this study, our goal was to generate a chimeric adenovirus-parvovirus (Ad-PV) vector that combines the high-titer and efficient gene transfer of adenovirus with the anticancer potential of rodent parvovirus. To this end, the entire oncolytic PV genome was inserted into a replication-defective E1- and E3-deleted Ad5 vector genome. As we found that parvoviral NS expression inhibited Ad-PV chimera production, we engineered the parvoviral P4 early promoter, which governs NS expression, by inserting into its sequence tetracycline operator elements. As a result of these modifications, P4-driven expression was blocked in the packaging T-REx-293 cells, which constitutively express the tetracycline repressor, allowing high-yield chimera production. The chimera effectively delivered the PV genome into cancer cells, from which fully infectious replication-competent parvovirus particles were generated. Remarkably, the Ad-PV chimera exerted stronger cytotoxic activities against various cancer cell lines, compared with the PV and Ad parental viruses, while being still innocuous to a panel of tested healthy primary human cells. This Ad-PV chimera represents a novel versatile anticancer agent which can be subjected to further genetic manipulations in order to reinforce its enhanced oncolytic capacity through arming with transgenes or retargeting into tumor cells.

  11. Chimera-like states in a neuronal network model of the cat brain

    Science.gov (United States)

    Santos, M. S.; Szezech, J. D.; Borges, F. S.; Iarosz, K. C.; Caldas, I. L.; Batista, A. M.; Viana, R. L.; Kurths, J.

    2017-08-01

    Neuronal systems have been modeled by complex networks in different description levels. Recently, it has been verified that networks can simultaneously exhibit one coherent and other incoherent domain, known as chimera states. In this work, we study the existence of chimera states in a network considering the connectivity matrix based on the cat cerebral cortex. The cerebral cortex of the cat can be separated in 65 cortical areas organised into the four cognitive regions: visual, auditory, somatosensory-motor and frontolimbic. We consider a network where the local dynamics is given by the Hindmarsh-Rose model. The Hindmarsh-Rose equations are a well known model of neuronal activity that has been considered to simulate membrane potential in neuron. Here, we analyse under which conditions chimera states are present, as well as the affects induced by intensity of coupling on them. We observe the existence of chimera states in that incoherent structure can be composed of desynchronised spikes or desynchronised bursts. Moreover, we find that chimera states with desynchronised bursts are more robust to neuronal noise than with desynchronised spikes.

  12. CAPRRESI: Chimera Assembly by Plasmid Recovery and Restriction Enzyme Site Insertion.

    Science.gov (United States)

    Santillán, Orlando; Ramírez-Romero, Miguel A; Dávila, Guillermo

    2017-06-25

    Here, we present chimera assembly by plasmid recovery and restriction enzyme site insertion (CAPRRESI). CAPRRESI benefits from many strengths of the original plasmid recovery method and introduces restriction enzyme digestion to ease DNA ligation reactions (required for chimera assembly). For this protocol, users clone wildtype genes into the same plasmid (pUC18 or pUC19). After the in silico selection of amino acid sequence regions where chimeras should be assembled, users obtain all the synonym DNA sequences that encode them. Ad hoc Perl scripts enable users to determine all synonym DNA sequences. After this step, another Perl script searches for restriction enzyme sites on all synonym DNA sequences. This in silico analysis is also performed using the ampicillin resistance gene (ampR) found on pUC18/19 plasmids. Users design oligonucleotides inside synonym regions to disrupt wildtype and ampR genes by PCR. After obtaining and purifying complementary DNA fragments, restriction enzyme digestion is accomplished. Chimera assembly is achieved by ligating appropriate complementary DNA fragments. pUC18/19 vectors are selected for CAPRRESI because they offer technical advantages, such as small size (2,686 base pairs), high copy number, advantageous sequencing reaction features, and commercial availability. The usage of restriction enzymes for chimera assembly eliminates the need for DNA polymerases yielding blunt-ended products. CAPRRESI is a fast and low-cost method for fusing protein-coding genes.

  13. Growth promotion of genetically modified hematopoietic progenitors using an antibody/c-Mpl chimera.

    Science.gov (United States)

    Kawahara, Masahiro; Chen, Jianhong; Sogo, Takahiro; Teng, Jinying; Otsu, Makoto; Onodera, Masafumi; Nakauchi, Hiromitsu; Ueda, Hiroshi; Nagamune, Teruyuki

    2011-09-01

    Thrombopoietin is a potent cytokine that exerts proliferation of hematopoietic stem cells (HSCs) through its cognate receptor, c-Mpl. Therefore, mimicry of c-Mpl signaling by a receptor recognizing an artificial ligand would be attractive to attain specific expansion of genetically modified HSCs. Here we propose a system enabling selective expansion of genetically modified cells using an antibody/receptor chimera that can be activated by a specific antigen. We constructed an antibody/c-Mpl chimera, in which single-chain Fv (ScFv) of an anti-fluorescein antibody was tethered to the extracellular D2 domain of the erythropoietin receptor and transmembrane/cytoplasmic domains of c-Mpl. When the chimera was expressed in interleukin (IL)-3-dependent pro-B cell line Ba/F3, genetically modified cells were selectively expanded in the presence of fluorescein-conjugated BSA (BSA-FL) as a specific antigen. Furthermore, highly purified mouse HSCs transduced with the retrovirus carrying antibody/c-Mpl chimera gene proliferated in vitro in response to BSA-FL, and the cells retained in vivo long-term repopulating abilities. These results demonstrate that the antibody/c-Mpl chimera is capable of signal transduction that mimics wild-type c-Mpl signaling. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Engineering human cytochrome P450 enzymes into catalytically self-sufficient chimeras using molecular Lego.

    Science.gov (United States)

    Dodhia, Vikash Rajnikant; Fantuzzi, Andrea; Gilardi, Gianfranco

    2006-10-01

    The membrane-bound human cytochrome P450s have essential roles in the metabolism of endogenous compounds and drugs. Presented here are the results on the construction and characterization of three fusion proteins containing the N-terminally modified human cytochrome P450s CYP2C9, CY2C19 and CYP3A4 fused to the soluble NADPH-dependent oxidoreductase domain of CYP102A1 from Bacillus megaterium. The constructs, CYP2C9/BMR, CYP2C19/BMR and CYP3A4/BMR are well expressed in Escherichia coli as holo proteins. The chimeras can be purified in the absence of detergent and the purified enzymes are both active and correctly folded in the absence of detergent, as demonstrated by circular dichroism and functional studies. Additionally, in comparison with the parent P450 enzyme, these chimeras have greatly improved solubility properties. The chimeras are catalytically self-sufficient and present turnover rates similar to those reported for the native enzymes in reconstituted systems, unlike previously reported mammalian cytochrome P450 fusion proteins. Furthermore the specific activities of these chimeras are not dependent on the enzyme concentration present in the reaction buffer and they do not require the addition of accessory proteins, detergents or phospholipids to be fully active. The solubility, catalytic self-sufficiency and wild-type like activities of these chimeras would greatly simplify the studies of cytochrome P450 mediated drug metabolism in solution.

  15. Endothelial cell repopulation after stenting determines in-stent neointima formation: effects of bare-metal vs. drug-eluting stents and genetic endothelial cell modification.

    Science.gov (United States)

    Douglas, Gillian; Van Kampen, Erik; Hale, Ashley B; McNeill, Eileen; Patel, Jyoti; Crabtree, Mark J; Ali, Ziad; Hoerr, Robert A; Alp, Nicholas J; Channon, Keith M

    2013-11-01

    Understanding endothelial cell repopulation post-stenting and how this modulates in-stent restenosis is critical to improving arterial healing post-stenting. We used a novel murine stent model to investigate endothelial cell repopulation post-stenting, comparing the response of drug-eluting stents with a primary genetic modification to improve endothelial cell function. Endothelial cell repopulation was assessed en face in stented arteries in ApoE(-/-) mice with endothelial-specific LacZ expression. Stent deployment resulted in near-complete denudation of endothelium, but was followed by endothelial cell repopulation, by cells originating from both bone marrow-derived endothelial progenitor cells and from the adjacent vasculature. Paclitaxel-eluting stents reduced neointima formation (0.423 ± 0.065 vs. 0.240 ± 0.040 mm(2), P = 0.038), but decreased endothelial cell repopulation (238 ± 17 vs. 154 ± 22 nuclei/mm(2), P = 0.018), despite complete strut coverage. To test the effects of selectively improving endothelial cell function, we used transgenic mice with endothelial-specific overexpression of GTP-cyclohydrolase 1 (GCH-Tg) as a model of enhanced endothelial cell function and increased NO production. GCH-Tg ApoE(-/-) mice had less neointima formation compared with ApoE(-/-) littermates (0.52 ± 0.08 vs. 0.26 ± 0.09 mm(2), P = 0.039). In contrast to paclitaxel-eluting stents, reduced neointima formation in GCH-Tg mice was accompanied by increased endothelial cell coverage (156 ± 17 vs. 209 ± 23 nuclei/mm(2), P = 0.043). Drug-eluting stents reduce not only neointima formation but also endothelial cell repopulation, independent of strut coverage. In contrast, selective targeting of endothelial cell function is sufficient to improve endothelial cell repopulation and reduce neointima formation. Targeting endothelial cell function is a rational therapeutic strategy to improve vascular healing and decrease neointima formation after stenting.

  16. Blood and Bone Marrow Donation

    Science.gov (United States)

    ... for a stem cell transplant. Risks Bone marrow donation The most serious risk associated with donating bone ... you feel fully recovered. Peripheral blood stem cell donation The risks of this type of stem cell ...

  17. MRI in bone marrow lesions

    International Nuclear Information System (INIS)

    Linden, A.; Theissen, P.; Schauerte, G.; Schicha, H.; Diehl, V.

    1989-01-01

    MRI has the potential to demonstrate bone marrow pathology due to its good soft tissue contrast. Inflammation and necrosis can be detected very early before there is evidence of radiological changes. In bone tumors intramedullary infiltration can be visualized in addition to soft tissue changes. Metastases of bone and bone marrow, especially in spinal and pelvic regions, are well depicted, often before bone scintigraphy yields pathological findings. In haematological disorders MRI permits follow-up studies due to its good reproducibility. Infiltration by malignant lymphoma and multiple myeloma and its extension in bone marrow can be visualized by MRI, too. However, the most common pathological MRI findings in bone marrow are not very specific, and final diagnosis requires further clinical or histological information. (orig.) [de

  18. Granulocyte-mobilized bone marrow.

    Science.gov (United States)

    Arcese, William; De Angelis, Gottardo; Cerretti, Raffaella

    2012-11-01

    In the last few years, mobilized peripheral blood has overcome bone marrow as a graft source, but, despite the evidence of a more rapid engraftment, the incidence of chronic graft-versus-host disease is significantly higher with, consequently, more transplant-related mortality on the long follow-up. Overall, the posttransplant outcome of mobilized peripheral blood recipients is similar to that of patients who are bone marrow grafted. More recently, the use of bone marrow after granulocyte colony-stimulating factor (G-CSF) donor priming has been introduced in the transplant practice. Herein, we review biological acquisitions and clinical results on the use of G-CSF-primed bone marrow as a source of hematopoietic stem cells (HSC) for allogeneic stem cell transplantation. G-CSF the increases the HSC compartment and exerts an intense immunoregulatory effect on marrow T-cells resulting in the shift from Th1 to Th2 phenotype with higher production of anti-inflammatory cytokines. The potential advantages of these biological effects have been translated in the clinical practice by using G-CSF primed unmanipulated bone marrow in the setting of transplant from human leukocyte antigen (HLA)-haploidentical donor with highly encouraging results. For patients lacking an HLA-identical sibling, the transplant of G-CSF primed unmanipulated bone marrow from a haploidentical donor combined with an intense in-vivo immunosuppression is a valid alternative achieving results that are well comparable with those reported for umbilical cord blood, HLA-matched unrelated peripheral blood/bone marrow or T-cell-depleted haploidentical transplant.

  19. HLA in bone marrow transplantation

    International Nuclear Information System (INIS)

    Tsuji, Kimiyoshi

    1989-01-01

    It has been well understood that human major histocompatibility antigen system, HLA is the most important role in the allo transplantation. Therefore, the structure of HLA genes was presented by the recent information (1987). Moreover, their functions in vitro and in vivo also were described. Finally, bone marrow transplantation and HLA network system in Japan against HLA mismatched case was proposed. It is eagerly expected that functional and clinical bone marrow transplantation in Japan could be succeeded. (author)

  20. THE PATHOLOGY OF BONE MARROW FAILURE

    OpenAIRE

    Leguit , Roos; Van Den Tweel , Jan G

    2010-01-01

    Abstract An important indication for bone marrow investigation is the presence of bone marrow failure, which manifests itself as (pan)cytopenia. The causes of cytopenia are varied and differ considerable between childhood and adulthood. In the paediatric age group, inherited bone marrow failure syndromes are important causes of bone marrow failure but they play only a minor role in later life. This review gives a comprehensive overview of bone marrow failure disorders in children a...

  1. Autologous bone marrow purging with LAK cells.

    Science.gov (United States)

    Giuliodori, L; Moretti, L; Stramigioli, S; Luchetti, F; Annibali, G M; Baldi, A

    1993-12-01

    In this study we will demonstrate that LAK cells, in vitro, can lyse hematologic neoplastic cells with a minor toxicity of the staminal autologous marrow cells. In fact, after bone marrow and LAK co-culture at a ratio of 1/1 for 8 hours, the inhibition on the GEMM colonies resulted to be 20% less compared to the untreated marrow. These data made LAK an inviting agent for marrow purging in autologous bone marrow transplantation.

  2. Evolution of endothelial keratoplasty.

    Science.gov (United States)

    Price, Francis W; Price, Marianne O

    2013-11-01

    Endothelial keratoplasty has evolved into a popular alternative to penetrating keratoplasty (PK) for the treatment of endothelial dysfunction. Although the earliest iterations were challenging and were not widely adopted, the iteration known as Descemet stripping endothelial keratoplasty (DSEK) has gained widespread acceptance. DSEK combines a simplified technique for stripping dysfunctional endothelium from the host cornea and microkeratome dissection of the donor tissue, a step now commonly completed in advance by eye bank technicians. Studies show that a newer endothelial keratoplasty iteration, known as Descemet membrane endothelial keratoplasty (DMEK), provides an even faster and better visual recovery than DSEK does. In addition, DMEK significantly reduces the risk of immunologic graft rejection episodes compared with that in DSEK or in PK. Although the DMEK donor tissue, consisting of the bare endothelium and Descemet membrane without any stroma, is more challenging to prepare and position in the recipient eye, recent improvements in instrumentation and surgical techniques are increasing the ease and the reliability of the procedure. DSEK successfully mitigates 2 of the main liabilities of PK: ocular surface complications and structural problems (including induced astigmatism and perpetually weak wounds), whereas DMEK further mitigates the 2 principal remaining liabilities of PK: immunologic graft reactions and secondary glaucoma from prolonged topical corticosteroid use.

  3. Trifluoperazine: corneal endothelial phototoxicity

    International Nuclear Information System (INIS)

    Hull, D.S.; Csukas, S.; Green, K.

    1983-01-01

    Trifluoperazine is used for the treatment of psychiatric disorders. Perfusion of corneal endothelial cells with trifluoperazine-HC1 concurrent with exposure to long wavelength ultraviolet light resulted in a corneal swelling rate greater than that found in perfused corneas not exposed to ultraviolet light. Exposure of endothelial cells to 25 W incandescent light during perfusion with trifluoperazine-HC1 did not result in a higher corneal swelling rate compared to those perfused in the dark. The increased corneal swelling rate could be produced by pre-exposure of the trifluoperazine-HC1 perfusing solution to ultraviolet light suggesting the production of toxic photoproducts during exposure of trifluoperazine-HC1 to ultraviolet light. Perfusion of corneal endothelial cells with non-ultraviolet illuminated trifluoperazine-HC1 had no effect on endothelial cell membranes or ultrastructure. This is in contrast to cells perfused with trifluoperazine-HC1 that had been exposed to ultraviolet light in which there was an alteration of mitochondria and a loss of cytoplasmic homogeneity. The data imply that the trifluoperazine-HC1 photoproduct had an adverse effect on cellular transport mechanisms. The study also further demonstrates the value of the corneal endothelial cell model for identifying the physiological and anatomical changes occuring in photo-induced toxic reactions. (author)

  4. Mitochondria and Endothelial Function

    Science.gov (United States)

    Kluge, Matthew A.; Fetterman, Jessica L.; Vita, Joseph A.

    2013-01-01

    In contrast to their role in other cell types with higher energy demands, mitochondria in endothelial cells primarily function in signaling cellular responses to environmental cues. This article provides an overview of key aspects of mitochondrial biology in endothelial cells, including subcellular location, biogenesis, dynamics, autophagy, ROS production and signaling, calcium homeostasis, regulated cell death, and heme biosynthesis. In each section, we introduce key concepts and then review studies showing the importance of that mechanism to endothelial control of vasomotor tone, angiogenesis, and inflammatory activation. We particularly highlight the small number of clinical and translational studies that have investigated each mechanism in human subjects. Finally, we review interventions that target different aspects of mitochondrial function and their effects on endothelial function. The ultimate goal of such research is the identification of new approaches for therapy. The reviewed studies make it clear that mitochondria are important in endothelial physiology and pathophysiology. A great deal of work will be needed, however, before mitochondria-directed therapies are available for the prevention and treatment of cardiovascular disease. PMID:23580773

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  7. Immunosuppression prior to marrow transplantation for sensitized aplastic anemia patients: comparison of TLI with TBI

    International Nuclear Information System (INIS)

    Shank, B.; Brochstein, J.A.; Castro-Malaspina, H.; Yahalom, J.; Bonfiglio, P.; O'Reilly, R.J.

    1988-01-01

    From May 1980 through July 1986, 26 patients with severe aplastic anemia, sensitized with multiple transfusions of blood products, were treated on either of two immunosuppressive regimens in preparation for bone marrow transplantation from a matched donor. There were 10 patients treated with total body irradiation (TBI), 200 cGy/fraction X 4 daily fractions (800 cGy total dose), followed by cyclophosphamide, 60 mg/kg/d X 2 d. An additional 16 patients were treated with total lymphoid irradiation (TLI) [or, if they were infants, a modified TLI or thoracoabdominal irradiation (TAI)], 100 cGy/fraction, 3 fractions/d X 2 d (600 cGy total dose), followed by cyclophosphamide, 40 mg/kg/d X 4 d. The extent of immunosuppression was similar in both groups as measured by peripheral blood lymphocyte depression at the completion of the course of irradiation (5% of initial concentration for TBI and 24% for TLI), neutrophil engraftment (10/10 for TBI and 15/16 for TLI), and time to neutrophil engraftment (median of 22 d for TBI and 17 d for TLI). Marrow and peripheral blood cytogenetic analysis for assessment of percent donor cells was also compared in those patients in whom it was available. 2/2 patients studied with TBI had 100% donor cells, whereas 6/11 with TLI had 100% donor cells. Of the five who did not, three were stable mixed chimeras with greater than or equal to 70% donor cells, one became a mixed chimera with about 50% donor cells, but became aplastic again after Cyclosporine A cessation 5 mo post-transplant, and the fifth reverted to all host cells by d. 18 post-transplant. Overall actuarial survival at 2 years was 56% in the TLI group compared with 30% in the TBI group although this was not statistically significant. No survival decrement has been seen after 2 years in either group

  8. Chimera states in a multilayer network of coupled and uncoupled neurons

    Science.gov (United States)

    Majhi, Soumen; Perc, Matjaž; Ghosh, Dibakar

    2017-07-01

    We study the emergence of chimera states in a multilayer neuronal network, where one layer is composed of coupled and the other layer of uncoupled neurons. Through the multilayer structure, the layer with coupled neurons acts as the medium by means of which neurons in the uncoupled layer share information in spite of the absence of physical connections among them. Neurons in the coupled layer are connected with electrical synapses, while across the two layers, neurons are connected through chemical synapses. In both layers, the dynamics of each neuron is described by the Hindmarsh-Rose square wave bursting dynamics. We show that the presence of two different types of connecting synapses within and between the two layers, together with the multilayer network structure, plays a key role in the emergence of between-layer synchronous chimera states and patterns of synchronous clusters. In particular, we find that these chimera states can emerge in the coupled layer regardless of the range of electrical synapses. Even in all-to-all and nearest-neighbor coupling within the coupled layer, we observe qualitatively identical between-layer chimera states. Moreover, we show that the role of information transmission delay between the two layers must not be neglected, and we obtain precise parameter bounds at which chimera states can be observed. The expansion of the chimera region and annihilation of cluster and fully coherent states in the parameter plane for increasing values of inter-layer chemical synaptic time delay are illustrated using effective range measurements. These results are discussed in the light of neuronal evolution, where the coexistence of coherent and incoherent dynamics during the developmental stage is particularly likely.

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

    International Nuclear Information System (INIS)

    Jerzy, M.; Zalewska, M.; Garczewska, A.

    1994-01-01

    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 vM 1 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 vM 1 generation. (author)

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

    Science.gov (United States)

    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.

  11. Polariton Chimeras: Bose-Einstein Condensates with Intrinsic Chaoticity and Spontaneous Long-Range Ordering

    Science.gov (United States)

    Gavrilov, S. S.

    2018-01-01

    The system of cavity polaritons driven by a plane electromagnetic wave is found to undergo the spontaneous breaking of spatial symmetry, which results in a lifted phase locking with respect to the driving field and, consequently, in the possibility of internal ordering. In particular, periodic spin and intensity patterns arise in polariton wires; they exhibit strong long-range order and can serve as media for signal transmission. Such patterns have the properties of dynamical chimeras: they are formed spontaneously in perfectly homogeneous media and can be partially chaotic. The reported new mechanism of chimera formation requires neither time-delayed feedback loops nor nonlocal interactions.

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

    International Nuclear Information System (INIS)

    Singh, V.P.; Yadav, R.D.S.

    1993-01-01

    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 M 1 and chlorophyll mutations in M 2 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

  13. Wine and endothelial function.

    Science.gov (United States)

    Caimi, G; Carollo, C; Lo Presti, R

    2003-01-01

    In recent years many studies have focused on the well-known relationship between wine consumption and cardiovascular risk. Wine exerts its protective effects through various changes in lipoprotein profile, coagulation and fibrinolytic cascades, platelet aggregation, oxidative mechanisms and endothelial function. The last has earned more attention for its implications in atherogenesis. Endothelium regulates vascular tone by a delicate balancing among vasorelaxing (nitric oxide [NO]) and vasoconstrincting (endothelins) factors produced by endothelium in response to various stimuli. In rat models, wine and other grape derivatives exerted an endothelium-dependent vasorelaxing capacity especially associated with the NO-stimulating activity of their polyphenol components. In experimental conditions, reservatrol (a stilbene polyphenol) protected hearts and kidneys from ischemia-reperfusion injury through antioxidant activity and upregulation of NO production. Wine polyphenols are also able to induce the expression of genes involved in the NO pathway within the arterial wall. The effects of wine on endothelial function in humans are not yet clearly understood. A favorable action of red wine or dealcoholized wine extract or purple grape juice on endothelial function has been observed by several authors, but discrimination between ethanol and polyphenol effects is controversial. It is, however likely that regular and prolonged moderate wine drinking positively affects endothelial function. The beneficial effects of wine on cardiovascular health are greater if wine is associated with a healthy diet. The most recent nutritional and epidemiologic studies show that the ideal diet closely resembles the Mediterranean diet.

  14. Infections and endothelial cells

    NARCIS (Netherlands)

    Keller, Tymen T.; Mairuhu, Albert T. A.; de Kruif, Martijn D.; Klein, Saskia K.; Gerdes, Victor E. A.; ten Cate, Hugo; Brandjes, Dees P. M.; Levi, Marcel; van Gorp, Eric C. M.

    2003-01-01

    Systemic infection by various pathogens interacts with the endothelium and may result in altered coagulation, vasculitis and atherosclerosis. Endothelium plays a role in the initiation and regulation of both coagulation and fibrinolysis. Exposure of endothelial cells may lead to rapid activation of

  15. Maintenance of host leukocytes in peripheral immune compartments following lethal irradiation and bone marrow reconstitution: implications for graft versus host disease.

    Science.gov (United States)

    Staley, Elizabeth M; Tanner, Scott M; Daft, Joseph G; Stanus, Andrea L; Martin, Steven M; Lorenz, Robin G

    2013-03-01

    Bone marrow reconstitution is utilized as a tool for disease treatment and as a research technique to elucidate the function of bone marrow derived cells. Clinically successful engraftment is indicated by the development of a functioning immune repertoire. In research, reconstitution is considered successful if >85% of splenic leukocytes are of donor origins. Previous work suggests that splenic reconstitution may not be indicative of reconstitution in the mucosa. We sought to evaluate mucosal reconstitution in animals following a standard bone marrow eradication and reconstitution technique. Bone marrow was harvested from adult B6.SJL donor mice (CD45.1) and injected via either the retro-orbital or intraperitoneal route into lethally irradiated B6 (CD45.2) adult or neonatal recipients respectively. The expression of CD45 by flow cytometry was used to calculate reconstitution with respect to immune compartment and cell type. In reconstituted adult animals 93.2±1.5% of splenic leukocytes expressed the donor CD45.1 antigen thus meeting the standard definition of reconstitution, however only 58.6±13.6% of intestinal lamina propria lymphocytes and 52.4±16.0% of intestinal intraepithelial lymphocytes were of donor origin, confirming splenic reconstitution fails to represent peripheral immune reconstitution. T-cells in the gastrointestinal tract are the most poorly reconstituted, while B-cells appear to be almost universally replaced by donor cells. The inadequate mucosal reconstitution was not corrected by evaluating later time points or by performing the bone marrow transfer during the neonatal period. This demonstration that substantial host T-cells remain in the intestinal mucosa after a "successful" bone marrow transplantation should cause a re-evaluation of data from research bone marrow chimera experiments, as well as the mechanisms for complications after clinical bone marrow transplantation. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Estradiol-induced, endothelial progenitor cell-mediated neovascularization in male mice with hind-limb ischemia

    NARCIS (Netherlands)

    Ruifrok, Willem-Peter T.; de Boer, Rudolf A.; Iwakura, Atsushi; Silver, Marcy; Kusano, Kengo; Tio, Rene A.; Losordo, Douglas W.

    We investigated whether administration of estradiol to male mice augments mobilization of bone marrow-derived endothelial progenitor cells (EPC) and incorporation into foci of neovascularization after hind-limb ischemia, thereby contributing to blood flow restoration. Mice were randomized and

  17. Diversity of chimera-like patterns from a model of 2D arrays of neurons with nonlocal coupling

    Science.gov (United States)

    Tian, Chang-Hai; Zhang, Xi-Yun; Wang, Zhen-Hua; Liu, Zong-Hua

    2017-06-01

    Chimera states have been studied in 1D arrays, and a variety of different chimera states have been found using different models. Research has recently been extended to 2D arrays but only to phase models of them. Here, we extend it to a nonphase model of 2D arrays of neurons and focus on the influence of nonlocal coupling. Using extensive numerical simulations, we find, surprisingly, that this system can show most types of previously observed chimera states, in contrast to previous models, where only one or a few types of chimera states can be observed in each model. We also find that this model can show some special chimera-like patterns such as gridding and multicolumn patterns, which were previously observed only in phase models. Further, we present an effective approach, i.e., removing some of the coupling links, to generate heterogeneous coupling, which results in diverse chimera-like patterns and even induces transformations from one chimera-like pattern to another.

  18. Bone and marrow dose modeling

    International Nuclear Information System (INIS)

    Stabin, Michael G.

    2004-01-01

    Nuclear medicine therapy is being used increasingly in the treatment of cancer (thyroid, leukemia/lymphoma with RIT, primary and secondary bone malignancies, and neuroblastomas). In all cases it is marrow toxicity that limits the amount of treatment that can be administered safely. Marrow dose calculations are more difficult than for many major organs because of the intricate association of bone and soft tissue elements. In RIT, there appears to be no consensus on how to calculate that dose accurately, or of individual patients ability to tolerate planned therapy. Available dose models are designed after an idealized average, healthy individual. Patient-specific methods are applied in evaluation of biokinetic data, and need to be developed for treatment of the physical data (dose conversion factors) as well: age, prior patient therapy, disease status. Contributors to marrow dose: electrons and photons

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

    Science.gov (United States)

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

    International Nuclear Information System (INIS)

    Martinez, Elisabeth D.; Pattabiraman, Nagarajan; Danielsen, Mark

    2005-01-01

    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

  1. Growth control of genetically modified cells using an antibody/c-Kit chimera.

    Science.gov (United States)

    Kaneko, Etsuji; Kawahara, Masahiro; Ueda, Hiroshi; Nagamune, Teruyuki

    2012-05-01

    Gene therapy has been regarded as an innovative potential treatment against serious congenital diseases. However, applications of gene therapy remain limited, partly because its clinical success depends on therapeutic gene-transduced cells acquiring a proliferative advantage. To address this problem, we have developed the antigen-mediated genetically modified cell amplification (AMEGA) system, which uses chimeric receptors to enable the selective proliferation of gene-transduced cells. In this report, we describe mimicry of c-Kit signaling and its application to the AMEGA system. We created an antibody/c-Kit chimera in which the extracellular domain of c-Kit is replaced with an anti-fluorescein single-chain Fv antibody fragment and the extracellular D2 domain of the erythropoietin receptor. A genetically modified mouse pro-B cell line carrying this chimera showed selective expansion in the presence of fluorescein-conjugated BSA (BSA-FL) as a growth inducer. By further engineering the transmembrane domain of the chimera to reduce interchain interaction we attained stricter ligand-dependency. Since c-Kit is an important molecule in the expansion of hematopoietic stem cells (HSCs), this antibody/c-Kit chimera could be a promising tool for gene therapy targeting HSCs. Copyright © 2011 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

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

    International Nuclear Information System (INIS)

    Fink, P.J.; Bevan, M.J.

    1981-01-01

    Recent experiments with murine radiation chimeras have shown that F 1 T cells that mature in an H-2 homozygous thymus, as is the case in [F 1 → 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

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

    Science.gov (United States)

    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.

  4. Interaction of chimera states in a multilayered network of nonlocally coupled oscillators

    Science.gov (United States)

    Goremyko, M. V.; Maksimenko, V. A.; Makarov, V. V.; Ghosh, D.; Bera, B.; Dana, S. K.; Hramov, A. E.

    2017-08-01

    The processes of formation and evolution of chimera states in the model of a multilayered network of nonlinear elements with complex coupling topology are studied. A two-layered network of nonlocally intralayer-coupled Kuramoto-Sakaguchi phase oscillators is taken as the object of investigation. Different modes implemented in this system upon variation of the degree of interlayer interaction are demonstrated.

  5. Chimera at the phase-flip transition of an ensemble of identical nonlinear oscillators

    Science.gov (United States)

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

    2018-06-01

    A complex collective emerging behavior characterized by coexisting coherent and incoherent domains is termed as a chimera state. We bring out the existence of a new type of chimera in a nonlocally coupled ensemble of identical oscillators driven by a common dynamic environment. The latter facilitates the onset of phase-flip bifurcation/transitions among the coupled oscillators of the ensemble, while the nonlocal coupling induces a partial asynchronization among the out-of-phase synchronized oscillators at this onset. This leads to the manifestation of coexisting out-of-phase synchronized coherent domains interspersed by asynchronous incoherent domains elucidating the existence of a different type of chimera state. In addition to this, a rich variety of other collective behaviors such as clusters with phase-flip transition, conventional chimera, solitary state and complete synchronized state which have been reported using different coupling architectures are found to be induced by the employed couplings for appropriate coupling strengths. The robustness of the resulting dynamics is demonstrated in ensembles of two paradigmatic models, namely Rössler oscillators and Stuart-Landau oscillators.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  8. Transfer to Intermediate Forms Following Concept Discrimination by Pigeons: Chimeras and Morphs

    Science.gov (United States)

    Ghosh, Natasha; Lea, S. E. G.; Noury, Malia

    2004-01-01

    Two experiments examined pigeons' generalization to intermediate forms following training of concept discriminations. In Experiment 1, the training stimuli were sets of images of dogs and cats, and the transfer stimuli were head/body chimeras, which humans tend to categorize more readily in terms of the head part rather than the body part. In…

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

    Science.gov (United States)

    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.

  10. A Phase 1 Study of 4 Live, Recombinant Human Cytomegalovirus Towne/Toledo Chimera Vaccines in Cytomegalovirus-Seronegative Men.

    Science.gov (United States)

    Adler, Stuart P; Manganello, Anne-Marie; Lee, Ronzo; McVoy, Michael A; Nixon, Daniel E; Plotkin, Stanley; Mocarski, Edward; Cox, Josephine H; Fast, Patricia E; Nesterenko, Pavlo A; Murray, Susan E; Hill, Ann B; Kemble, George

    2016-11-01

     Human cytomegalovirus (HCMV) infection causes disease in newborns and transplant recipients. A HCMV vaccine (Towne) protects transplant recipients.  The genomes of Towne and the nonattenuated Toledo strain were recombined, yielding 4 Towne/Toledo chimera vaccines. Each of 36 HCMV-seronegative men received 1 subcutaneous dose of 10, 100, or 1000 plaque-forming units (PFU) in cohorts of 3. Safety and immunogenicity were evaluated over 12 weeks after immunization and for 52 weeks for those who seroconverted.  There were no serious local or systemic reactions. No subject had HCMV in urine or saliva. For chimera 3, none of 9 subjects seroconverted. For chimera 1, 1 of 9 seroconverted (the seroconverter received 100 PFU). For chimera 2, 3 subjects seroconverted (1 received 100 PFU, and 2 received 1000 PFU). For chimera 4, 7 subjects seroconverted (1 received 10 PFU, 3 received 100 PFU, and 3 received 1000 PFU). All 11 seroconverters developed low but detectable levels of neutralizing activity. CD4 + T-cell responses were detectable in 1 subject (who received 100 PFU of chimera 4). Seven subjects receiving chimera 2 or 4 had detectable CD8 + T-cell responses to IE1; 3 responded to 1-2 additional antigens.  The Towne/Toledo chimera vaccine candidates were well tolerated and were not excreted. Additional human trials of chimeras 2 and 4 are appropriate.  NCT01195571. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  11. Widespread marrow necrosis during pregnancy

    International Nuclear Information System (INIS)

    Knickerbocker, W.J.; Quenville, N.F.

    1982-01-01

    Recently, a 22-year-old Caucasian female was referred to our Hospital two days post-partum. She had been feeling unwell during the last few days of her pregnancy and complained of multiple aches and pains, worst in the abdomen and lower back. Her admission platelet count was severely depressed and a bone biopsy showed extensive marrow necrosis with viable bony trabeculae. There was no evidence of vasculitis, vascular thrombosis, or malignancy. Widespread marrow necrosis in pregnancy followed by recovery, to our knowledge, has not been previously reported. (orig.)

  12. Gametocytes of the Malaria Parasite Plasmodium falciparum Interact With and Stimulate Bone Marrow Mesenchymal Cells to Secrete Angiogenetic Factors

    Directory of Open Access Journals (Sweden)

    Valeria Messina

    2018-03-01

    Full Text Available The gametocytes of Plasmodium falciparum, responsible for the transmission of this malaria parasite from humans to mosquitoes, accumulate and mature preferentially in the human bone marrow. In the 10 day long sexual development of P. falciparum, the immature gametocytes reach and localize in the extravascular compartment of this organ, in contact with several bone marrow stroma cell types, prior to traversing the endothelial lining and re-entering in circulation at maturity. To investigate the host parasite interplay underlying this still obscure process, we developed an in vitro tridimensional co-culture system in a Matrigel scaffold with P. falciparum gametocytes and self-assembling spheroids of human bone marrow mesenchymal cells (hBM-MSCs. Here we show that this co-culture system sustains the full maturation of the gametocytes and that the immature, but not the mature, gametocytes adhere to hBM-MSCs via trypsin-sensitive parasite ligands exposed on the erythrocyte surface. Analysis of a time course of gametocytogenesis in the co-culture system revealed that gametocyte maturation is accompanied by the parasite induced stimulation of hBM-MSCs to secrete a panel of 14 cytokines and growth factors, 13 of which have been described to play a role in angiogenesis. Functional in vitro assays on human bone marrow endothelial cells showed that supernatants from the gametocyte mesenchymal cell co-culture system enhance ability of endothelial cells to form vascular tubes. These results altogether suggest that the interplay between immature gametocytes and hBM-MSCs may induce functional and structural alterations in the endothelial lining of the human bone marrow hosting the P. falciparum transmission stages.

  13. Tumor endothelial markers define novel subsets of cancer-specific circulating endothelial cells associated with antitumor efficacy

    Science.gov (United States)

    Mehran, Reza; Nilsson, Monique; Khajavi, Mehrdad; Du, Zhiqiang; Cascone, Tina; Wu, Hua Kang; Cortes, Andrea; Xu, Li; Zurita, Amado; Schier, Robert; Riedel, Bernhard; El-Zein, Randa; Heymach, John V.

    2014-01-01

    Circulating endothelial cells (CEC) are derived from multiple sources including bone marrow (circulating endothelial progenitors [CEP]) and established vasculature (mature CEC). Although CEC have shown promise as a biomarker for cancer patients, their utility has been limited in part by the lack of specificity for tumor vasculature and the different non-malignant causes that can impact CEC. Tumor endothelial markers (TEM) are antigens enriched in tumor vs non-malignant endothelia. We hypothesized that TEMs may be detectable on CEC and that these circulating TEM+ endothelial cells (CTEC) may be a more specific marker for cancer and tumor response than standard CEC. We found that tumor-bearing mice had a relative increase in numbers of circulating CTEC, specifically with increased levels of TEM7 and TEM8 expression. Following treatment with various vascular targeting agents, we observed a decrease in CTEC that correlated with the reductions in tumor growth. We extended these findings to human clinical samples and observed that CTEC were present in esophageal cancer and non-small cell lung cancer (NSCLC) patients (N=40) and their levels decreased after surgical resection. These results demonstrate that CTEC are detectable in preclinical cancer models and cancer patients. Further, they suggest that CTEC offer a novel cancer-associated marker that may be useful as a blood-based surrogate for assessing the presence of tumor vasculature and antiangiogenic drug activity. PMID:24626092

  14. Germline competence of mouse ES and iPS cell lines: Chimera technologies and genetic background.

    Science.gov (United States)

    Carstea, Ana Claudia; Pirity, Melinda K; Dinnyes, Andras

    2009-12-31

    In mice, gene targeting by homologous recombination continues to play an essential role in the understanding of functional genomics. This strategy allows precise location of the site of transgene integration and is most commonly used to ablate gene expression ("knock-out"), or to introduce mutant or modified alleles at the locus of interest ("knock-in"). The efficacy of producing live, transgenic mice challenges our understanding of this complex process, and of the factors which influence germline competence of embryonic stem cell lines. Increasingly, evidence indicates that culture conditions and in vitro manipulation can affect the germline-competence of Embryonic Stem cell (ES cell) lines by accumulation of chromosome abnormalities and/or epigenetic alterations of the ES cell genome. The effectiveness of ES cell derivation is greatly strain-dependent and it may also influence the germline transmission capability. Recent technical improvements in the production of germline chimeras have been focused on means of generating ES cells lines with a higher germline potential. There are a number of options for generating chimeras from ES cells (ES chimera mice); however, each method has its advantages and disadvantages. Recent developments in induced pluripotent stem (iPS) cell technology have opened new avenues for generation of animals from genetically modified somatic cells by means of chimera technologies. The aim of this review is to give a brief account of how the factors mentioned above are influencing the germline transmission capacity and the developmental potential of mouse pluripotent stem cell lines. The most recent methods for generating specifically ES and iPS chimera mice, including the advantages and disadvantages of each method are also discussed.

  15. Bone marrow edema of the knee joint

    International Nuclear Information System (INIS)

    Breitenseher, M.J.; Mayerhoefer, M.E.; Hofmann, S.

    2006-01-01

    Bone marrow edema of the knee joint is a frequent clinical picture in MR diagnostics. It can be accompanied by symptoms and pain in the joint. Diseases that are associated with bone marrow edema can be classified into different groups. Group 1 includes vascular ischemic bone marrow edema with osteonecrosis (synonyms: SONK or Ahlbaeck's disease), osteochondrosis dissecans, and bone marrow edema syndrome. Group 2 comprises traumatic or mechanical bone marrow edema. Group 3 encompasses reactive bone marrow edemas such as those occurring in gonarthrosis, postoperative bone marrow edemas, and reactive edemas in tumors or tumorlike diseases. Evidence for bone marrow edema is effectively provided by MRI, but purely morphological MR information is often unspecific so that anamnestic and clinical details are necessary in most cases for definitive disease classification. (orig.) [de

  16. Bone-marrow transplant - series (image)

    Science.gov (United States)

    Bone-marrow transplants are performed for: deficiencies in red blood cells (aplastic anemia) and white blood cells (leukemia or ... Bone-marrow transplants prolong the life of patients who might otherwise die. As with all major organ transplants, however, ...

  17. Mechanisms of cardiac transplantation tolerance in syngeneic rat radiation chimeras

    International Nuclear Information System (INIS)

    Moran, T.M.

    1981-01-01

    Seventy-five percent of adult LEW rats, lethally irradiated (860 R), transplanted with an RT-1 incompatible Wistar Furth (WF) heart or kidney and repopulated on day 2 with a 4:1 mixture of syngeneic thymus and bone marrow cells accept these grafts. In order to look at the ability of animals tolerating WF organ grafts to respond against WF spleen cells in vitro we developed a rat mixed lymphocyte culture. Tolerant animals were tested for the ability to respond to donor antigens and approximately half of the 50 animals tested, were responsive. We attempted to demonstrate suppressor cells which might be responsible for maintaining tolerance in the nonresponders. Neither mixtures at the sensitization or the effector level suggested that tolerance was being maintained by a suppressor cell. An in vivo assay which tested the ability of various cell populations to affect the survival of allogeneic hearts transplanted into sublethally irradiated recipients was then employed. Tolerance is induced using this protocol in a manner similar or identical to tolerance produced by neonatal injection of antigen. This tolerance might be maintained in part by suppressor cells which prevents the generation of clones of cells reactive against the heart donor. The mechanism of tolerance in rats with demonstrable clones of reactive cells remains to be determined

  18. Contribution of Mouse Embryonic Stem Cells and Induced Pluripotent Stem Cells to Chimeras through Injection and Coculture of Embryos

    OpenAIRE

    Guo, Jitong; Wu, Baojiang; Li, Shuyu; Bao, Siqin; Zhao, Lixia; Hu, Shuxiang; Sun, Wei; Su, Jie; Dai, Yanfeng; Li, Xihe

    2014-01-01

    Blastocyst injection and morula aggregation are commonly used to evaluate stem cell pluripotency based on chimeric contribution of the stem cells. To assess the protocols for generating chimeras from stem cells, 8-cell mouse embryos were either injected or cocultured with mouse embryonic stem cells and induced pluripotent stem cells, respectively. Although a significantly higher chimera rate resulted from blastocyst injection, the highest germline contribution resulted from injection of 8-cel...

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

    International Nuclear Information System (INIS)

    Obasaju, M.F.; Wiley, L.M.; Oudiz, D.J.; Miller, L.; Samuels, S.J.; Chang, R.J.; Overstreet, J.W.

    1988-01-01

    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

  20. Engraftment of allogeneic bone marrow without graft-versus-host disease in mongrel dogs using total lymphoid irradiation

    International Nuclear Information System (INIS)

    Gottlieb, M.; Strober, S.; Hoppe, R.T.; Grumet, F.C.; Kaplan, H.S.

    1980-01-01

    We achieved long-term engraftment of unmatched bone marrow (BM) in dogs without graft-versus-host disease (GVHD) using a regimen of total lymphoid irradiation (TLI) which could be applied clinically. Twelve normal adult mongrel dogs were given TLI in 18 fractions of 100 rad each (total dose, 1800 rad) over 4 weeks to mantle and abdominal fields in continuity. Nine of the 12 were transfused with one or two random donor whole blood transfusions during the irradiation regimen to determine the risk of sensitization after the onset of immunosuppression. A mean (+- SD) of 0.71 +- 0.54 x 10 9 BM cells/kg of recipient body weight from unrelated sex-mismatched donors was infused within 24 h of the 18th irradiation fraction. Engraftment was assessed by demonstration of donor-type sex chromosomes in spontaneous metaphase spreads of recipient marrow aspirates, and by the appearance of donor-type red blood cells antigens (DEA) in the recipients' blood. Three untransfused and nine transfused recipients were shown to be stable mixed BM chimeras during a followup period of 2 to 11 months after transplantation. Blood transfusion during TLI did not result in graft rejection. We observed no clinical signs of acute or chronic GVHD. TLI has minimal toxicity when compared with conditioning regimens currently used in BM transplantation for aplastic anemia. Potential advantages of the TLI regimen include the opportunity to use unmatched marrow donors and protection from GVHD

  1. Booster irradiation to the spleen following total body irradiation. A new immunosuppressive approach for allogeneic bone marrow transplantation

    International Nuclear Information System (INIS)

    Lapidot, T.; Singer, T.S.; Salomon, O.; Terenzi, A.; Schwartz, E.; Reisner, Y.

    1988-01-01

    Graft rejection presents a major obstacle for transplantation of T cell-depleted bone marrow in HLA-mismatched patients. In a primate model, after conditioning exactly as for leukemia patients, it was shown that over 99% of the residual host clonable T cells are concentrated in the spleen on day 5 after completion of cytoreduction. We have now corroborated these findings in a mouse model. After 9-Gy total body irradiation (TBI), the total number of Thy-1.2+ cells in the spleen reaches a peak between days 3 and 4 after TBI. The T cell population is composed of both L3T4 (helper) and Lyt-2 (suppressor) T cells, the former being the major subpopulation. Specific booster irradiation to the spleen (5 Gy twice) on days 2 and 4 after TBI greatly enhances production of donor-type chimera after transplantation of T cell-depleted allogeneic bone marrow. Similar enhancement can be achieved by splenectomy on day 3 or 4 after TBI but not if splenectomy is performed 1 day before TBI or 1 day after TBI, strengthening the hypothesis that, after lethal TBI in mice, the remaining host T cells migrate from the periphery to the spleen. These results suggest that a delayed booster irradiation to the spleen may be beneficial as an additional immunosuppressive agent in the conditioning of leukemia patients, in order to reduce the incidence of bone marrow allograft rejection

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

    International Nuclear Information System (INIS)

    Beschorner, W.E.; Tutschka, P.J.; Santos, G.W.

    1982-01-01

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    Beschorner, W.E.; Tutschka, P.J.; Santos, G.W.

    1982-04-01

    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. Endothelial RIG-I activation impairs endothelial function

    Energy Technology Data Exchange (ETDEWEB)

    Asdonk, Tobias, E-mail: tobias.asdonk@ukb.uni-bonn.de [Department of Medicine/Cardiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Motz, Inga; Werner, Nikos [Department of Medicine/Cardiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Coch, Christoph; Barchet, Winfried; Hartmann, Gunther [Institute for Clinical Chemistry and Clinical Pharmacology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Nickenig, Georg; Zimmer, Sebastian [Department of Medicine/Cardiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany)

    2012-03-30

    Highlights: Black-Right-Pointing-Pointer RIG-I activation impairs endothelial function in vivo. Black-Right-Pointing-Pointer RIG-I activation alters HCAEC biology in vitro. Black-Right-Pointing-Pointer EPC function is affected by RIG-I stimulation in vitro. -- Abstract: Background: Endothelial dysfunction is a crucial part of the chronic inflammatory atherosclerotic process and is mediated by innate and acquired immune mechanisms. Recent studies suggest that pattern recognition receptors (PRR) specialized in immunorecognition of nucleic acids may play an important role in endothelial biology in a proatherogenic manner. Here, we analyzed the impact of endothelial retinoic acid inducible gene I (RIG-I) activation upon vascular endothelial biology. Methods and results: Wild type mice were injected intravenously with 32.5 {mu}g of the RIG-ligand 3pRNA (RNA with triphosphate at the 5 Prime end) or polyA control every other day for 7 days. In 3pRNA-treated mice, endothelium-depended vasodilation was significantly impaired, vascular oxidative stress significantly increased and circulating endothelial microparticle (EMP) numbers significantly elevated compared to controls. To gain further insight in RIG-I dependent endothelial biology, cultured human coronary endothelial cells (HCAEC) and endothelial progenitor cells (EPC) were stimulated in vitro with 3pRNA. Both cells types express RIG-I and react with receptor upregulation upon stimulation. Reactive oxygen species (ROS) formation is enhanced in both cell types, whereas apoptosis and proliferation is not significantly affected in HCAEC. Importantly, HCAEC release significant amounts of proinflammatory cytokines in response to RIG-I stimulation. Conclusion: This study shows that activation of the cytoplasmatic nucleic acid receptor RIG-I leads to endothelial dysfunction. RIG-I induced endothelial damage could therefore be an important pathway in atherogenesis.

  5. Endothelial RIG-I activation impairs endothelial function

    International Nuclear Information System (INIS)

    Asdonk, Tobias; Motz, Inga; Werner, Nikos; Coch, Christoph; Barchet, Winfried; Hartmann, Gunther; Nickenig, Georg; Zimmer, Sebastian

    2012-01-01

    Highlights: ► RIG-I activation impairs endothelial function in vivo. ► RIG-I activation alters HCAEC biology in vitro. ► EPC function is affected by RIG-I stimulation in vitro. -- Abstract: Background: Endothelial dysfunction is a crucial part of the chronic inflammatory atherosclerotic process and is mediated by innate and acquired immune mechanisms. Recent studies suggest that pattern recognition receptors (PRR) specialized in immunorecognition of nucleic acids may play an important role in endothelial biology in a proatherogenic manner. Here, we analyzed the impact of endothelial retinoic acid inducible gene I (RIG-I) activation upon vascular endothelial biology. Methods and results: Wild type mice were injected intravenously with 32.5 μg of the RIG-ligand 3pRNA (RNA with triphosphate at the 5′end) or polyA control every other day for 7 days. In 3pRNA-treated mice, endothelium-depended vasodilation was significantly impaired, vascular oxidative stress significantly increased and circulating endothelial microparticle (EMP) numbers significantly elevated compared to controls. To gain further insight in RIG-I dependent endothelial biology, cultured human coronary endothelial cells (HCAEC) and endothelial progenitor cells (EPC) were stimulated in vitro with 3pRNA. Both cells types express RIG-I and react with receptor upregulation upon stimulation. Reactive oxygen species (ROS) formation is enhanced in both cell types, whereas apoptosis and proliferation is not significantly affected in HCAEC. Importantly, HCAEC release significant amounts of proinflammatory cytokines in response to RIG-I stimulation. Conclusion: This study shows that activation of the cytoplasmatic nucleic acid receptor RIG-I leads to endothelial dysfunction. RIG-I induced endothelial damage could therefore be an important pathway in atherogenesis.

  6. The marrow heterotopia in thalassemia

    International Nuclear Information System (INIS)

    Papavasiliou, C.; Gouliamos, A.; Andreou, J.

    1986-01-01

    The subject of marrow heterotopia has been reviewed on the basis of 15 cases suffering from thalassemia. Other cases reported in the literature were also reviewed. Using conventional radiography, scintigraphy, computerized tomography and myelography, 17% of the cases admitted into the hospital with the diagnosis of Thalassemia, were found to have macroscopic masses of marrow heterotopia. The most common site of development of these masses was the costovertebral gutter, followed by the anterior end of the ribs and the extradural space of the spinal canal. In one case, masses were located in the maxillary antra. The clinical implications, the pathogenesis of the masses and the differential diagnosis from other tumour-like entities are discussed. Three patients presented with symptoms and signs of spinal cord compression. All three patients were treated satisfactorily with small doses of radiotherapy. (orig.)

  7. Gillick, bone marrow and teenagers.

    Science.gov (United States)

    Cherkassky, Lisa

    2015-09-01

    The Human Tissue Authority can authorise a bone marrow harvest on a child of any age if a person with parental responsibility consents to the procedure. Older children have the legal capacity to consent to medical procedures under Gillick, but it is unclear if Gillick can be applied to non-therapeutic medical procedures. The relevant donation guidelines state that the High Court shall be consulted in the event of a disagreement, but what is in the best interests of the teenage donor under s.1 of the Children Act 1989? There are no legal authorities on child bone marrow harvests in the United Kingdom. This article considers the best interests of the older saviour sibling and questions whether, for the purposes of welfare, the speculative benefits could outweigh the physical burdens. © The Author(s) 2015.

  8. The contribution of human/non-human animal chimeras to stem cell research

    Directory of Open Access Journals (Sweden)

    Sonya Levine

    2017-10-01

    Full Text Available Chimeric animals are made up of cells from two separate zygotes. Human/non-human animal chimeras have been used for a number of research purposes, including human disease modeling. Pluripotent stem cell (PSC research has relied upon the chimera approach to examine the developmental potential of stem cells, to determine the efficacy of cell replacement therapies, and to establish a means of producing human organs. Based on ethical issues, this work has faced pushback from various sources including funding agencies. We discuss here the essential role these studies have played, from gaining a better understanding of human biology to providing a stepping stone to human disease treatments. We also consider the major ethical issues, as well as the current status of support for this work in the United States.

  9. The contribution of human/non-human animal chimeras to stem cell research.

    Science.gov (United States)

    Levine, Sonya; Grabel, Laura

    2017-10-01

    Chimeric animals are made up of cells from two separate zygotes. Human/non-human animal chimeras have been used for a number of research purposes, including human disease modeling. Pluripotent stem cell (PSC) research has relied upon the chimera approach to examine the developmental potential of stem cells, to determine the efficacy of cell replacement therapies, and to establish a means of producing human organs. Based on ethical issues, this work has faced pushback from various sources including funding agencies. We discuss here the essential role these studies have played, from gaining a better understanding of human biology to providing a stepping stone to human disease treatments. We also consider the major ethical issues, as well as the current status of support for this work in the United States. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  10. Chaos in Dirac Electron Optics: Emergence of a Relativistic Quantum Chimera.

    Science.gov (United States)

    Xu, Hong-Ya; Wang, Guang-Lei; Huang, Liang; Lai, Ying-Cheng

    2018-03-23

    We uncover a remarkable quantum scattering phenomenon in two-dimensional Dirac material systems where the manifestations of both classically integrable and chaotic dynamics emerge simultaneously and are electrically controllable. The distinct relativistic quantum fingerprints associated with different electron spin states are due to a physical mechanism analogous to a chiroptical effect in the presence of degeneracy breaking. The phenomenon mimics a chimera state in classical complex dynamical systems but here in a relativistic quantum setting-henceforth the term "Dirac quantum chimera," associated with which are physical phenomena with potentially significant applications such as enhancement of spin polarization, unusual coexisting quasibound states for distinct spin configurations, and spin selective caustics. Experimental observations of these phenomena are possible through, e.g., optical realizations of ballistic Dirac fermion systems.

  11. Chaos in Dirac Electron Optics: Emergence of a Relativistic Quantum Chimera

    Science.gov (United States)

    Xu, Hong-Ya; Wang, Guang-Lei; Huang, Liang; Lai, Ying-Cheng

    2018-03-01

    We uncover a remarkable quantum scattering phenomenon in two-dimensional Dirac material systems where the manifestations of both classically integrable and chaotic dynamics emerge simultaneously and are electrically controllable. The distinct relativistic quantum fingerprints associated with different electron spin states are due to a physical mechanism analogous to a chiroptical effect in the presence of degeneracy breaking. The phenomenon mimics a chimera state in classical complex dynamical systems but here in a relativistic quantum setting—henceforth the term "Dirac quantum chimera," associated with which are physical phenomena with potentially significant applications such as enhancement of spin polarization, unusual coexisting quasibound states for distinct spin configurations, and spin selective caustics. Experimental observations of these phenomena are possible through, e.g., optical realizations of ballistic Dirac fermion systems.

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

    Science.gov (United States)

    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.

  13. Chimera states in multi-strain epidemic models with temporary immunity

    Science.gov (United States)

    Bauer, Larissa; Bassett, Jason; Hövel, Philipp; Kyrychko, Yuliya N.; Blyuss, Konstantin B.

    2017-11-01

    We investigate a time-delayed epidemic model for multi-strain diseases with temporary immunity. In the absence of cross-immunity between strains, dynamics of each individual strain exhibit emergence and annihilation of limit cycles due to a Hopf bifurcation of the endemic equilibrium, and a saddle-node bifurcation of limit cycles depending on the time delay associated with duration of temporary immunity. Effects of all-to-all and non-local coupling topologies are systematically investigated by means of numerical simulations, and they suggest that cross-immunity is able to induce a diverse range of complex dynamical behaviors and synchronization patterns, including discrete traveling waves, solitary states, and amplitude chimeras. Interestingly, chimera states are observed for narrower cross-immunity kernels, which can have profound implications for understanding the dynamics of multi-strain diseases.

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

    Science.gov (United States)

    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.

  15. In vivo differentiation of induced pluripotent stem cells into neural stem cells by chimera formation.

    Science.gov (United States)

    Choi, Hyun Woo; Hong, Yean Ju; Kim, Jong Soo; Song, Hyuk; Cho, Ssang Gu; Bae, Hojae; Kim, Changsung; Byun, Sung June; Do, Jeong Tae

    2017-01-01

    Like embryonic stem cells, induced pluripotent stem cells (iPSCs) can differentiate into all three germ layers in an in vitro system. Here, we developed a new technology for obtaining neural stem cells (NSCs) from iPSCs through chimera formation, in an in vivo environment. iPSCs contributed to the neural lineage in the chimera, which could be efficiently purified and directly cultured as NSCs in vitro. The iPSC-derived, in vivo-differentiated NSCs expressed NSC markers, and their gene-expression pattern more closely resembled that of fetal brain-derived NSCs than in vitro-differentiated NSCs. This system could be applied for differentiating pluripotent stem cells into specialized cell types whose differentiation protocols are not well established.

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

    Science.gov (United States)

    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.

  17. Chimera states in brain networks: Empirical neural vs. modular fractal connectivity

    Science.gov (United States)

    Chouzouris, Teresa; Omelchenko, Iryna; Zakharova, Anna; Hlinka, Jaroslav; Jiruska, Premysl; Schöll, Eckehard

    2018-04-01

    Complex spatiotemporal patterns, called chimera states, consist of coexisting coherent and incoherent domains and can be observed in networks of coupled oscillators. The interplay of synchrony and asynchrony in complex brain networks is an important aspect in studies of both the brain function and disease. We analyse the collective dynamics of FitzHugh-Nagumo neurons in complex networks motivated by its potential application to epileptology and epilepsy surgery. We compare two topologies: an empirical structural neural connectivity derived from diffusion-weighted magnetic resonance imaging and a mathematically constructed network with modular fractal connectivity. We analyse the properties of chimeras and partially synchronized states and obtain regions of their stability in the parameter planes. Furthermore, we qualitatively simulate the dynamics of epileptic seizures and study the influence of the removal of nodes on the network synchronizability, which can be useful for applications to epileptic surgery.

  18. Multi-dimensional simulations of core-collapse supernova explosions with CHIMERA

    Science.gov (United States)

    Messer, O. E. B.; Harris, J. A.; Hix, W. R.; Lentz, E. J.; Bruenn, S. W.; Mezzacappa, A.

    2018-04-01

    Unraveling the core-collapse supernova (CCSN) mechanism is a problem that remains essentially unsolved despite more than four decades of effort. Spherically symmetric models with otherwise high physical fidelity generally fail to produce explosions, and it is widely accepted that CCSNe are inherently multi-dimensional. Progress in realistic modeling has occurred recently through the availability of petascale platforms and the increasing sophistication of supernova codes. We will discuss our most recent work on understanding neutrino-driven CCSN explosions employing multi-dimensional neutrino-radiation hydrodynamics simulations with the Chimera code. We discuss the inputs and resulting outputs from these simulations, the role of neutrino radiation transport, and the importance of multi-dimensional fluid flows in shaping the explosions. We also highlight the production of 48Ca in long-running Chimera simulations.

  19. Gene expression analysis of embryonic stem cells expressing VE-cadherin (CD144 during endothelial differentiation

    Directory of Open Access Journals (Sweden)

    Libermann Towia

    2008-05-01

    Full Text Available Abstract Background Endothelial differentiation occurs during normal vascular development in the developing embryo. This process is recapitulated in the adult when endothelial progenitor cells are generated in the bone marrow and can contribute to vascular repair or angiogenesis at sites of vascular injury or ischemia. The molecular mechanisms of endothelial differentiation remain incompletely understood. Novel approaches are needed to identify the factors that regulate endothelial differentiation. Methods Mouse embryonic stem (ES cells were used to further define the molecular mechanisms of endothelial differentiation. By flow cytometry a population of VEGF-R2 positive cells was identified as early as 2.5 days after differentiation of ES cells, and a subset of VEGF-R2+ cells, that were CD41 positive at 3.5 days. A separate population of VEGF-R2+ stem cells expressing the endothelial-specific marker CD144 (VE-cadherin was also identified at this same time point. Channels lined by VE-cadherin positive cells developed within the embryoid bodies (EBs formed by differentiating ES cells. VE-cadherin and CD41 expressing cells differentiate in close proximity to each other within the EBs, supporting the concept of a common origin for cells of hematopoietic and endothelial lineages. Results Microarray analysis of >45,000 transcripts was performed on RNA obtained from cells expressing VEGF-R2+, CD41+, and CD144+ and VEGF-R2-, CD41-, and CD144-. All microarray experiments were performed in duplicate using RNA obtained from independent experiments, for each subset of cells. Expression profiling confirmed the role of several genes involved in hematopoiesis, and identified several putative genes involved in endothelial differentiation. Conclusion The isolation of CD144+ cells during ES cell differentiation from embryoid bodies provides an excellent model system and method for identifying genes that are expressed during endothelial differentiation and that

  20. Emerging paradigms and questions on pro-angiogenic bone marrow-derived myelomonocytic cells.

    Science.gov (United States)

    Laurent, Julien; Touvrey, Cédric; Botta, Francesca; Kuonen, François; Ruegg, Curzio

    2011-01-01

    Cancer-related inflammation has emerged in recent years as a major event contributing to tumor angiogenesis, tumor progression and metastasis formation. Bone marrow-derived and inflammatory cells promote tumor angiogenesis by providing endothelial progenitor cells that differentiate into mature endothelial cells, and by secreting pro-angiogenic factors and remodeling the extracellular matrix to stimulate angiogenesis though paracrine mechanisms. Several bone marrow-derived myelonomocytic cells, including monocytes and macrophages, have been identified and characterized by several laboratories in recent years. While the central role of these cells in promoting tumor angiogenesis, tumor progression and metastasis is nowadays well established, many questions remain open and new ones are emerging. These include the relationship between their phenotype and function, the mechanisms of pro-angiogenic programming, their contribution to resistance to anti-angiogenic treatments and to metastasis and their potential clinical use as biomarkers of angiogenesis and anti-angiogenic therapies. Here, we will review phenotypical and functional aspects of bone marrow-derived myelonomocytic cells and discuss some of the current outstanding questions.

  1. Bone--bone marrow interactions

    International Nuclear Information System (INIS)

    Patt, H.M.

    1976-01-01

    Within medullary cavities, blood formation tends to be concentrated near bone surfaces and this raises interesting questions about hematopoietic consequences of radionuclide fixation in osseous tissue. Thus, it may be important, on the one hand, to consider the medullary radiation dose distribution as well as total marrow dose from bone-bound radioelements and, on the other, to inquire about possible hematopoietic implications of radiation damage to endosteal surfaces per se. The reasons for this are discussed

  2. Chaos in Dirac electron optics: Emergence of a relativistic quantum chimera

    OpenAIRE

    Xu, Hong-Ya; Wang, Guang-Lei; Huang, Liang; Lai, Ying-Cheng

    2018-01-01

    We uncover a remarkable quantum scattering phenomenon in two-dimensional Dirac material systems where the manifestations of both classically integrable and chaotic dynamics emerge simultaneously and are electrically controllable. The distinct relativistic quantum fingerprints associated with different electron spin states are due to a physical mechanism analogous to chiroptical effect in the presence of degeneracy breaking. The phenomenon mimics a chimera state in classical complex dynamical ...

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

    Directory of Open Access Journals (Sweden)

    V.B. CÂRSTEA

    2007-05-01

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Le Neindre, N.; Alderighi, M.; Anzalone, A.; Barna, R.; Bartolucci, M.; Berceanu, I.; Borderie, B.; Bougault, R.; Bruno, M.; Cardella, G.; Cavallaro, S.; D' Agostino, M. E-mail: dagostino@bo.infn.it; 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.; Lanzano, 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.; Trifiro, 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 {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. EXAMINATION OF THE GERM CELL CHIMERA FORMING POTENTIAL OF MOUSE EMBRYONIC STEM CELLS

    Directory of Open Access Journals (Sweden)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Semenova, N.; Anishchenko, V. [Department of Physics, Saratov State University, Astrakhanskaya Str. 83, 410012 Saratov (Russian Federation); Zakharova, A.; Schöll, E. [Institut für Theoretische Physik, TU Berlin, Hardenbergstraße 36, 10623 Berlin (Germany)

    2016-06-08

    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.

  7. Bone marrow edema in sports: General concepts

    International Nuclear Information System (INIS)

    Vanhoenacker, F.M.; Snoeckx, A.

    2007-01-01

    This paper will discuss the value of medical imaging in the detection and follow-up of bone marrow edema (BME), resulting from acute and chronic trauma in sports. MR imaging is the only imaging technique that allows direct evaluation of bone marrow edema in sports medicine. The use of fat suppressed T2-weighted or STIR images is particularly appropriate to detect bone marrow edema. The extent of bone marrow edema reflects the biomechanics of trauma. Compressive forces between two bony structures will result in extensive areas of bone marrow edema, whereas distraction forces provoke more subtle areas of bone marrow edema at the insertion of supporting structures of joints. In most clinical situations, a combination of compression and distraction forces is present, causing a complex pattern of bone marrow edema. A meticulous pattern approach of the distribution of these bone marrow changes around a joint can reveal in most instances the underlying mechanism of trauma. This may be helpful to analyze which joint supporting structures may be at risk. In the acute setting, plain radiography and CT scan may have an additional role in the detection of small avulsion fractures occurring at the site of minor areas of bone marrow edema. The clinical significance and natural history of bone marrow edema is still a matter of debate

  8. Bone marrow mesenchymal stem cells overexpressing human basic fibroblast growth factor increase vasculogenesis in ischemic rats

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, J.C. [Department of Vascular Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou (China); Zheng, G.F. [Department of Vascular Surgery, The People' s Hospital of Ganzhou, Ganzhou (China); Wu, L.; Ou Yang, L.Y.; Li, W.X. [Department of Vascular Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou (China)

    2014-08-08

    Administration or expression of growth factors, as well as implantation of autologous bone marrow cells, promote in vivo angiogenesis. This study investigated the angiogenic potential of combining both approaches through the allogenic transplantation of bone marrow-derived mesenchymal stem cells (MSCs) expressing human basic fibroblast growth factor (hbFGF). After establishing a hind limb ischemia model in Sprague Dawley rats, the animals were randomly divided into four treatment groups: MSCs expressing green fluorescent protein (GFP-MSC), MSCs expressing hbFGF (hbFGF-MSC), MSC controls, and phosphate-buffered saline (PBS) controls. After 2 weeks, MSC survival and differentiation, hbFGF and vascular endothelial growth factor (VEGF) expression, and microvessel density of ischemic muscles were determined. Stable hbFGF expression was observed in the hbFGF-MSC group after 2 weeks. More hbFGF-MSCs than GFP-MSCs survived and differentiated into vascular endothelial cells (P<0.001); however, their differentiation rates were similar. Moreover, allogenic transplantation of hbFGF-MSCs increased VEGF expression (P=0.008) and microvessel density (P<0.001). Transplantation of hbFGF-expressing MSCs promoted angiogenesis in an in vivo hind limb ischemia model by increasing the survival of transplanted cells that subsequently differentiated into vascular endothelial cells. This study showed the therapeutic potential of combining cell-based therapy with gene therapy to treat ischemic disease.

  9. Bone marrow mesenchymal stem cells overexpressing human basic fibroblast growth factor increase vasculogenesis in ischemic rats

    Directory of Open Access Journals (Sweden)

    J.C. Zhang

    2014-10-01

    Full Text Available Administration or expression of growth factors, as well as implantation of autologous bone marrow cells, promote in vivo angiogenesis. This study investigated the angiogenic potential of combining both approaches through the allogenic transplantation of bone marrow-derived mesenchymal stem cells (MSCs expressing human basic fibroblast growth factor (hbFGF. After establishing a hind limb ischemia model in Sprague Dawley rats, the animals were randomly divided into four treatment groups: MSCs expressing green fluorescent protein (GFP-MSC, MSCs expressing hbFGF (hbFGF-MSC, MSC controls, and phosphate-buffered saline (PBS controls. After 2 weeks, MSC survival and differentiation, hbFGF and vascular endothelial growth factor (VEGF expression, and microvessel density of ischemic muscles were determined. Stable hbFGF expression was observed in the hbFGF-MSC group after 2 weeks. More hbFGF-MSCs than GFP-MSCs survived and differentiated into vascular endothelial cells (P<0.001; however, their differentiation rates were similar. Moreover, allogenic transplantation of hbFGF-MSCs increased VEGF expression (P=0.008 and microvessel density (P<0.001. Transplantation of hbFGF-expressing MSCs promoted angiogenesis in an in vivo hind limb ischemia model by increasing the survival of transplanted cells that subsequently differentiated into vascular endothelial cells. This study showed the therapeutic potential of combining cell-based therapy with gene therapy to treat ischemic disease.

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

    Science.gov (United States)

    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.

  11. Three-dimensional chimera patterns in networks of spiking neuron oscillators

    Science.gov (United States)

    Kasimatis, T.; Hizanidis, J.; Provata, A.

    2018-05-01

    We study the stable spatiotemporal patterns that arise in a three-dimensional (3D) network of neuron oscillators, whose dynamics is described by the leaky integrate-and-fire (LIF) model. More specifically, we investigate the form of the chimera states induced by a 3D coupling matrix with nonlocal topology. The observed patterns are in many cases direct generalizations of the corresponding two-dimensional (2D) patterns, e.g., spheres, layers, and cylinder grids. We also find cylindrical and "cross-layered" chimeras that do not have an equivalent in 2D systems. Quantitative measures are calculated, such as the ratio of synchronized and unsynchronized neurons as a function of the coupling range, the mean phase velocities, and the distribution of neurons in mean phase velocities. Based on these measures, the chimeras are categorized in two families. The first family of patterns is observed for weaker coupling and exhibits higher mean phase velocities for the unsynchronized areas of the network. The opposite holds for the second family, where the unsynchronized areas have lower mean phase velocities. The various measures demonstrate discontinuities, indicating criticality as the parameters cross from the first family of patterns to the second.

  12. Human-animal chimera: a neuro driven discussion? Comparison of three leading European research countries.

    Science.gov (United States)

    Cabrera Trujillo, Laura Yenisa; Engel-Glatter, Sabrina

    2015-06-01

    Research with human-animal chimera raises a number of ethical concerns, especially when neural stem cells are transplanted into the brains of non-human primates (NHPs). Besides animal welfare concerns and ethical issues associated with the use of embryonic stem cells, the research is also regarded as controversial from the standpoint of NHPs developing cognitive or behavioural capabilities that are regarded as "unique" to humans. However, scientists are urging to test new therapeutic approaches for neurological diseases in primate models as they better mimic human physiology than all current animal models. As a response, various countries have issued reports on the topic. Our paper summarizes the ethical issues raised by research with human-animal brain chimeras and compares the relevant regulatory instruments and different recommendations issued in national reports from three important European research nations: Germany, Switzerland and the United Kingdom. We assess and discuss the focus and priorities set by the different reports, review various reasons for and perspectives on the importance of the brain in chimera research, and identify critical points in the reports that warrant further specification and debate.

  13. Serine integrase chimeras with activity in E. coli and HeLa cells

    Directory of Open Access Journals (Sweden)

    Alfonso P. Farruggio

    2014-09-01

    Full Text Available In recent years, application of serine integrases for genomic engineering has increased in popularity. The factor-independence and unidirectionality of these large serine recombinases makes them well suited for reactions such as site-directed vector integration and cassette exchange in a wide variety of organisms. In order to generate information that might be useful for altering the specificity of serine integrases and to improve their efficiency, we tested a hybridization strategy that has been successful with several small serine recombinases. We created chimeras derived from three characterized members of the serine integrase family, phiC31, phiBT1, and TG1 integrases, by joining their amino- and carboxy-terminal portions. We found that several phiBT1-phiC31 (BC and phiC31-TG1 (CT hybrid integrases are active in E. coli. BC chimeras function on native att-sites and on att-sites that are hybrids between those of the two donor enzymes, while CT chimeras only act on the latter att-sites. A BC hybrid, BC{−1}, was also active in human HeLa cells. Our work is the first to demonstrate chimeric serine integrase activity. This analysis sheds light on integrase structure and function, and establishes a potentially tractable means to probe the specificity of the thousands of putative large serine recombinases that have been revealed by bioinformatics studies.

  14. Bone marrow ablation with Ho-166 pharmaceuticals as preparation for bone marrow transplants

    International Nuclear Information System (INIS)

    Parks, N.J.; Kawakami, T.; Avila, M.; White, R.; Cain, G.; Moore, P.F.

    1991-01-01

    Bone marrow ablation is required preparation for leukemia patients where bone marrow transplantation is to be the therapeutic modality. Presently, the total body irradiation that is used produces appreciable morbidity in terms of radiation sickness, but an evenly distributed dose to marrow. The authors have shown in Beagles that bone-seeking radiolanthanide (Ho-166, t 1/2 = 25 h, 1.8 MeB beta, carrier added) phosphonic acid chelates can be used to completely ablate bone marrow with little morbidity. The research plan, incorporating bone marrow ablation with bone-seeking radionuclides and in vitro purging of aspirated leukemic marrow for use in autologous marrow transplants, is presented. Phosphonic acid complexes of Sm-153 also localize in the skeleton and have found use in the palliation of bone pain. However, the dose distribution is uneven because these radiopharmaceuticals distribute according to available surface; 2-4 times the skeletal average in trabecular vs cortical bone. Thus, the marrow dose can vary. The authors' research group and the Radiation Interactions Division of NIST have announced the discovery that beta radiation-induced excited electrons are trapped in the hydroxyapatite mineral of bone and provide a potential direct dosimetric method for marrow dose when combined with routine bone marrow (and included bone) biopsies. The overall research plan sets the hypothesis that reduced morbidity marrow ablation can be successfully followed by bone marrow transplantation (BMT) with autologous marrow purged in vitro by antibody-targeted alpha emitters

  15. Endothelial Jagged-1 Is Necessary for Homeostatic and Regenerative Hematopoiesis

    Directory of Open Access Journals (Sweden)

    Michael G. Poulos

    2013-09-01

    Full Text Available The bone marrow (BM microenvironment is composed of multiple niche cells that, by producing paracrine factors, maintain and regenerate the hematopoietic stem cell (HSC pool (Morrison and Spradling, 2008. We have previously demonstrated that endothelial cells support the proper regeneration of the hematopoietic system following myeloablation (Butler et al., 2010; Hooper et al., 2009; Kobayashi et al., 2010. Here, we demonstrate that expression of the angiocrine factor Jagged-1, supplied by the BM vascular niche, regulates homeostatic and regenerative hematopoiesis through a Notch-dependent mechanism. Conditional deletion of Jagged-1 in endothelial cells (Jag1(ECKO mice results in a profound decrease in hematopoiesis and premature exhaustion of the adult HSC pool, whereas quantification and functional assays demonstrate that loss of Jagged-1 does not perturb vascular or mesenchymal compartments. Taken together, these data demonstrate that the instructive function of endothelial-specific Jagged-1 is required to support the self-renewal and regenerative capacity of HSCs in the adult BM vascular niche.

  16. MR imaging of normal bone marrow

    International Nuclear Information System (INIS)

    Stajgis, M.; Paprzycki, W.

    1994-01-01

    Principles of MR bone marrow imaging on the basis of retrospective analysis of MR examinations of bone marrow in different anatomic sites in 200 patients have been discussed. Significance of different physiologic factors and processes such as age, steatosis, osteoporosis, conversion and reconversion, which influence on MR bone marrow images, have been emphasized. T1-weighted images obtained with spin-echo sequences give the most of information about bone marrow structure in MR. Thorough knowledge of bone marrow physiology and clinical status of the patient is indispensable in correct interpretation of hypointensive lesions on T1-weighted images. When presence of disseminated bone marrow disease is suspected, authors propose routine imaging of lumbar vertebral column, pelvis and proximal parts of femoral bones. (author)

  17. Constitutive production and thrombin-induced release of vascular endothelial growth factor by human megakaryocytes and platelets

    Science.gov (United States)

    Möhle, Robert; Green, David; Moore, Malcolm A. S.; Nachman, Ralph L.; Rafii, Shahin

    1997-01-01

    We have shown that coculture of bone marrow microvascular endothelial cells with hematopoietic progenitor cells results in proliferation and differentiation of megakaryocytes. In these long-term cultures, bone marrow microvascular endothelial cell monolayers maintain their cellular integrity in the absence of exogenous endothelial growth factors. Because this interaction may involve paracrine secretion of cytokines, we evaluated megakaryocytic cells for secretion of vascular endothelial growth factor (VEGF). Megakaryocytes (CD41a+) were generated by ex vivo expansion of hematopoietic progenitor cells with kit-ligand and thrombopoietin for 10 days and further purified with immunomagnetic microbeads. Using reverse transcription–PCR, we showed that megakaryocytic cell lines (Dami, HEL) and purified megakaryocytes expressed mRNA of the three VEGF isoforms (121, 165, and 189 amino acids). Large quantities of VEGF (>1 ng/106 cells/3 days) were detected in the supernatant of Dami cells, ex vivo-generated megakaryocytes, and CD41a+ cells isolated from bone marrow. The constitutive secretion of VEGF by CD41a+ cells was stimulated by growth factors of the megakaryocytic lineage (interleukin 3, thrombopoietin). Western blotting of heparin–Sepharose-enriched supernatant mainly detected the isoform VEGF165. In addition, immunohistochemistry showed intracytoplasmic VEGF in polyploid megakaryocytes. Thrombin stimulation of megakaryocytes and platelets resulted in rapid release of VEGF within 30 min. We conclude that human megakaryocytes produce and secrete VEGF in an inducible manner. Within the bone marrow microenvironment, VEGF secreted by megakaryocytes may contribute to the proliferation of endothelial cells. VEGF delivered to sites of vascular injury by activated platelets may initiate angiogenesis. PMID:9012841

  18. MR appearances of bone marrow in children following bone marrow transplantation

    International Nuclear Information System (INIS)

    Boothroyd, A.E.; Sebag, G.; Brunelle, F.

    1991-01-01

    Two cases are presented of children who demonstrated complete absence of bone marrow signal on MR imaging of the spine following bone marrow transplantation. The possible causes for these appearances are discussed. (orig.)

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

    LENUS (Irish Health Repository)

    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.

  20. Patterns of bone-marrow scintigraphy

    International Nuclear Information System (INIS)

    Touya, J.J.; Lee, G.S.; Narvaez, M.; Marciano, D.

    1977-01-01

    111 In-transferrin, radiocolloid and bone scans were performed within one week on 105 from more than 250 scanned patients with different haematological disorders. All patients had complete haematological workups and confirmed final diagnoses. From the comparison of the 111 In-transferrin marrow scan with the radiocolloid marrow scan and bone scan, eight basic patterns of localized or generalized disorders in the bone marrow cell production were delineated. The first pattern was called a cold area and two sub-patterns were distinguished in it. A cold area in the erythropoietic and reticuloendothelial scans associated with cold or normal areas in the bone scan corresponded to radiation damage of the marrow or multiple myeloma; a cold area in both marrow scans with a hot area in the bone scan to tumour, infarct and bone trauma. The second pattern was called a hot area. A hot area in the two marrow scans with a normal bone scan was observed in islands of active bone-marrow. Hot areas in both 111 In-transferrin and bone scan associated with a cold area in the radiocolloid scan were observed in tumours growing in bones with or without little active bone marrow. Hot areas on the three scans were observed in osteomyelitis of bones of the extremities. The third pattern was bone-marrow expansion, which was observed in hereditary haemolytic anaemias, in myeloproliferative disorders and in patients with bone-marrow damage following irradiation. The fourth pattern was saturation of the serum iron-binding capacity and it was manifested by increased activity in the kidneys in the 111 In-transferrin scan. The fifth pattern was bone-marrow failure which consists of decreased accumulation in the marrow and increased accumulation in the liver of marrow-seeking agents associated with normal bone scan. The sixth pattern, pure red cell aplasia, was characterized by less accumulation of 111 In-transferrin than radiocolloid in the bone marrow. The seventh pattern, bone-marrow siderosis

  1. [Acute unclassified leukemia with bone marrow necrosis].

    Science.gov (United States)

    Uoshima, N; Yamazaki, N; Iinuma, S; Kimura, S; Wada, K; Kobayashi, Y; Ozawa, M; Horiuchi, H; Maruo, N; Kondo, M

    1991-01-01

    Massive bone marrow necrosis was seen in a 42-year-old male with acute leukemia. In December, 1988, on admission, laboratory data revealed pancytopenia and a high level of serum LDH and ALKP. Bone marrow aspiration resulted in dry-tap and showed bone marrow necrosis in the bone marrow biopsy specimen. A bone marrow scintigraphy with 111In faintly visualized the bone marrow but visualized area was expanded in the extremities compared with normal subjects. The second bone marrow biopsy showed proliferation of blasts. In the middle of March, blasts began to appear in peripheral blood. The blasts were cytochemically negative for POX, Es, PAS, AcP, TdT and had surface markers CD3-, CD19-, CD33-, CD13-, LCA-, HLA-DR-. Even by investigation on rearrangement of the immunoglobulin heavy chain region, an origin of the blasts could not be determined. In April, the number of blasts in peripheral blood increased and hepatosplenomegaly developed rapidly. Therefore, he was put on the chemotherapy with vincristine and prednisolone, but he died of cerebral hemorrhage. The autopsy revealed widespread bone marrow necrosis. It has rarely been reported that massive bone marrow necrosis is found prior to the occurrence of acute unclassified leukemia.

  2. Homing of bone marrow lymphoid cells

    International Nuclear Information System (INIS)

    Yoshida, Y.; Osmond, D.G.

    1978-01-01

    DNA labeling, bone marrow fractionation, and radioautography were used to follow the fate of transfused, newly formed marrow lymphocytes in irradiated hosts. After infusing donor Hartley guinea pigs with 3 H-thymidine for 3 to 5 days, high concentrations of labeled small lymphocytes and large lymphoid cells were separated from marrow by sedimentation in sucrose-serum gradients and injected into lethally x-irradiated syngeneic recipients. Most labeled small lymphocytes and large lymphoid cells rapidly left the circulation. They appeared to be mainly in the marrow and spleen, increasing in incidence from 1 to 3 days, but declining in mean grain count. Labeled cells were scattered throughout the recipient marrow; in the spleen they localized initially in the red pulp, and subsequently in peripheral areas of white pulp, often in clusters. Labeled small lymphocytes showed a delayed migration into the mesenteric lymph node, mainly in the superficial cortex and medulla; they also appeared in small numbers in Peyer's patches, but rarely in the thymus or thoracic duct lymph. It is concluded that a rapid selective homing of newly formed marrow lymphoid cells occurs in both the marrow and certain areas of the spleen of irradiated hosts, followed by a continuing proliferation of large lymphoid cells and production of small lymphocytes. The results are discussed with respect to the life history of marrow lymphocytes and the use of adoptive immune assays of marrow cells to characterize B lymphocyte maturation

  3. The Effects of Inhaled Nickel Nanoparticles on Murine Endothelial Progenitor Cells

    Science.gov (United States)

    Liberda, Eric N.

    Introduction. Particulate air pollution, specifically nickel found on or in particulate matter, has been associated with an increased risk of mortality in human population studies and can cause increases in vascular inflammation, generate reactive oxygen species, alter vasomotor tone, and potentiate atherosclerosis in murine exposures. With the discovery of endothelial progenitor cells (EPCs), a door has been opened which may explain these observed cardiovascular effects associated with inhaled air particles and nickel exposure. In order to further quantify the effects of inhaled nickel nanoparticles and attempt to elucidate how the observed findings from other studies may occur, several whole body inhalation exposure experiments to nickel nanoparticles were performed. Methods. Following whole body exposure to approximately 500mug/m3 of nickel nanoparticles for 5 hrs, bone marrow EPCs from C57BL/6 mice were isolated. EPCs were harvested for their RNA or used in a variety of assays including chemotaxis, tube formation, and proliferation. Gene expression was assessed for important receptors involved in EPC mobilization and homing using RT-PCR methods. EPCs, circulating endothelial progenitor cells, circulating endothelial cells (CECs), and endothelial microparticles (EMPs) were quantified on a BD FACSCalibur to examine endothelial damage and repair associated with the inhalation exposure. Plasma proteins were assessed using the 2D DIGE proteomic approach and commercially available ELISAs. Results and Conclusions. Exposure to inhaled nickel nanoparticles significantly increased both bone marrow EPCs as well as their levels in circulation. CECs were significantly upregulated suggesting that endothelial damage occurred due to the exposure. There was no significant difference in EMPs between the two groups. Tube formation and chemotaxis, but not proliferation, of bone marrow EPCs was impaired in the nickel nanoparticle exposed group. This decrease in EPC function

  4. 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

    DEFF Research Database (Denmark)

    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...

  5. Purification and characterization of Yersinia enterocolitica and Yersinia pestis LcrV-cholera toxin A(2)/B chimeras.

    Science.gov (United States)

    Tinker, Juliette K; Davis, Chadwick T; Arlian, Britni M

    2010-11-01

    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 A(2)/B chimeric molecules containing the LcrV protective antigen from Yersinia enterocolitica and Y. pestis. These chimeras were expressed and purified to high yields from the supernatant of transformed Escherichia coli. Western and GM(1) ELISA assays were used to characterize the composition, receptor-binding and relative stability of the LcrV-CTA(2)/B chimera in comparison to cholera toxin. In addition, we investigated the ability of the Y. pestis LcrV-CTA(2)/B chimera to bind to and internalize into cultured epithelial cells and macrophages by confocal microscopy. These studies indicate that the uptake and trafficking of the LcrV antigen from the chimera is comparable to the trafficking of native toxin. Together these findings report that stable, receptor-binding, non-toxic LcrV-cholera toxin A(2)/B chimeras can be expressed at high levels in E. coli and purified from the supernatant. In addition, the internalization of antigen in vitro reported here supports the development of these molecules as novel mucosal vaccine candidates. Copyright 2010 Elsevier Inc. All rights reserved.

  6. Bone marrow stromal cell transplantation mitigates radiation-induced gastrointestinal syndrome in mice.

    Directory of Open Access Journals (Sweden)

    Subhrajit Saha

    Full Text Available Nuclear accidents and terrorism presents a serious threat for mass casualty. While bone-marrow transplantation might mitigate hematopoietic syndrome, currently there are no approved medical countermeasures to alleviate radiation-induced gastrointestinal syndrome (RIGS, resulting from direct cytocidal effects on intestinal stem cells (ISC and crypt stromal cells. We examined whether bone marrow-derived adherent stromal cell transplantation (BMSCT could restitute irradiated intestinal stem cells niche and mitigate radiation-induced gastrointestinal syndrome.Autologous bone marrow was cultured in mesenchymal basal medium and adherent cells were harvested for transplantation to C57Bl6 mice, 24 and 72 hours after lethal whole body irradiation (10.4 Gy or abdominal irradiation (16-20 Gy in a single fraction. Mesenchymal, endothelial and myeloid population were characterized by flow cytometry. Intestinal crypt regeneration and absorptive function was assessed by histopathology and xylose absorption assay, respectively. In contrast to 100% mortality in irradiated controls, BMSCT mitigated RIGS and rescued mice from radiation lethality after 18 Gy of abdominal irradiation or 10.4 Gy whole body irradiation with 100% survival (p<0.0007 and p<0.0009 respectively beyond 25 days. Transplantation of enriched myeloid and non-myeloid fractions failed to improve survival. BMASCT induced ISC regeneration, restitution of the ISC niche and xylose absorption. Serum levels of intestinal radioprotective factors, such as, R-Spondin1, KGF, PDGF and FGF2, and anti-inflammatory cytokines were elevated, while inflammatory cytokines were down regulated.Mitigation of lethal intestinal injury, following high doses of irradiation, can be achieved by intravenous transplantation of marrow-derived stromal cells, including mesenchymal, endothelial and macrophage cell population. BMASCT increases blood levels of intestinal growth factors and induces regeneration of the irradiated

  7. Bone Marrow Transplantation: MedlinePlus Health Topic

    Science.gov (United States)

    ... marrow transplant - discharge (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Bone Marrow Transplantation ... transplant - slideshow Graft-versus-host disease Related Health Topics Bone Marrow Diseases Stem Cells National Institutes of ...

  8. Genetics Home Reference: Pearson marrow-pancreas syndrome

    Science.gov (United States)

    ... Health Conditions Pearson marrow-pancreas syndrome Pearson marrow-pancreas syndrome Printable PDF Open All Close All Enable ... view the expand/collapse boxes. Description Pearson marrow-pancreas syndrome is a severe disorder that usually begins ...

  9. Studies on the distribution of hematopoietic bone marrow by bone marrow scintigraphy, 2. The bone marrow distribution in leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Fujimori, K [Kyoto Univ. (Japan). Faculty of Medicine

    1976-04-01

    Distribution of the leukemic marrow was investigated in 42 cases by bone marrow scintigraphy using sup(99m)Tc sulfur colloid in association with clinical findings and ferrokinetics studies in order to clarify hematopoietic function in leukemia. 17 of chronic myelogenous leukemia, 3 of lymphatic leukemia, 2 of monocytic leukemia, 7 of atypical leukemia and one of erythroleukemia. 12 acute myelogenous leukemia were classified into 3 types A, B and C. Type A showed the distribution similar to those obtained with normal controls. Ferrokinetics studies, however, indicated complete absence of erythropoiesis. Type B showed complete lack of sup(99m)Tc activity in usual marrow sites, although ferrokinetics data showed normal erythropoeitic function. Type C showed abnormal concentration of sup(99m)Tc sulfur colloid in the tibiae. 17 chronic myelogenous leukemia showed reduced sup(99m)Tc activity in usual marrow sites and remarkable expanded marrow extending into distal femurs, proximal and distal tibiae and bones of feet. 2 acute lymphotic leukemia patients showed complete absence of sup(99m)Tc activity. The one chronic type showed almost normal distribution. Monocytic leukemia showed decreased marrow distribution in the sternum and vertebrae. Of 6 atypical leukemias one showed almost normal distribution. The others, including a case with hypoplastic luekemia, demonstrated marrow extension similar to that observed in chronic myelogenous leukemia or monocytic leukemia. Erythroleukemia showed increased concentrations of sup(99m)Tc activity in the usual marrow sites and marked marrow expansion throughout all long bones. These results suggest that there is a discrepancy between bone marrow distribution and hematopoietic function in the cases of acute myelogenous leukemia.

  10. Angiocrine factors from Akt-activated endothelial cells balance self-renewal and differentiation of haematopoietic stem cells

    Science.gov (United States)

    Kobayashi, Hideki; Butler, Jason M.; O'Donnell, Rebekah; Kobayashi, Mariko; Ding, Bi-Sen; Bonner, Bryant; Chiu, Vi K.; Nolan, Daniel J.; Shido, Koji; Benjamin, Laura; Rafii, Shahin

    2010-01-01

    Endothelial cells establish an instructive vascular niche that reconstitutes haematopoietic stem and progenitor cells (HSPCs) through release of specific paracrine growth factors, known as angiocrine factors. However, the mechanism by which endothelial cells balance the rate of proliferation and lineage-specific differentiation of HSPCs is unknown. Here, we demonstrate that Akt activation in endothelial cells, through recruitment of mTOR, but not the FoxO pathway, upregulates specific angiocrine factors that support expansion of CD34−Flt3− KLS HSPCs with long-term haematopoietic stem cell (LT-HSC) repopulation capacity. Conversely, co-activation of Akt-stimulated endothelial cells with p42/44 MAPK shifts the balance towards maintenance and differentiation of the HSPCs. Selective activation of Akt1 in the endothelial cells of adult mice increased the number of colony forming units in the spleen and CD34−Flt3− KLS HSPCs with LT-HSC activity in the bone marrow, accelerating haematopoietic recovery. Therefore, the activation state of endothelial cells modulates reconstitution of HSPCs through the upregulation of angiocrine factors, with Akt–mTOR-activated endothelial cells supporting the self-renewal of LT-HSCs and expansion of HSPCs, whereas MAPK co-activation favours maintenance and lineage-specific differentiation of HSPCs. PMID:20972423

  11. Magnetic resonance imaging of the bone marrow

    International Nuclear Information System (INIS)

    Baur-Melnyk, Andrea

    2013-01-01

    The first book devoted to MRI of the bone marrow. Describes the MRI appearances of normal bone marrows and the full range of bone marrow disorders. Discusses the role of advanced MRI techniques and contrast enhancement. On account of its unrivalled imaging capabilities and sensitivity, magnetic resonance imaging (MRI) is considered the modality of choice for the investigation of physiologic and pathologic processes affecting the bone marrow. This book describes the MRI appearances of both the normal bone marrow, including variants, and the full range of bone marrow disorders. Detailed discussion is devoted to malignancies, including multiple myeloma, lymphoma, chronic myeloproliferative disorders, leukemia, and bone metastases. Among the other conditions covered are benign and malignant compression fractures, osteonecrosis, hemolytic anemia, Gaucher's disease, bone marrow edema syndrome, trauma, and infective and non-infective inflammatory disease. Further chapters address the role of MRI in assessing treatment response, the use of contrast media, and advanced MRI techniques. Magnetic Resonance Imaging of the Bone Marrow represents an ideal reference for both novice and experienced practitioners.

  12. Inherited Bone Marrow Failure Syndromes (IBMFS)

    Science.gov (United States)

    The NCI IBMFS Cohort Study consists of affected individuals and their immediate families in North America who have an inherited bone marrow failure syndrome (IBMFS)-either one that has been specifically identified and defined, or bone marrow failure that appears to be inherited but has not yet been clearly identified as having a genetic basis.

  13. How to exhaust your bone marrow

    DEFF Research Database (Denmark)

    Salomo, Louise; Salomo, Morten; Andersen, Steven A W

    2013-01-01

    at work and in his spare time, and kept a very thorough training and weight diary. Owing to a high intake of energy and protein drinks he tried to optimise his physical performance and kept a normal body mass index  at 23.7. A bone marrow biopsy showed gelatinous bone marrow transformation, normally seen...

  14. Functional bone marrow scintigraphy in psoriatics

    International Nuclear Information System (INIS)

    Munz, D.; Altmeyer, P.; Chilf, G.; Schlesinger, G.; Holzmann, H.; Hoer, G.

    1982-01-01

    24 psoriatics as well as 24 normal healthy adults were studied by functional bone marrow scintigraphy using Tc-99m-labeled human serum albumin millimicrospheres (Tc-99m-HSA-MM). Functional bone marrow scintigraphy is an in vivo test system for the assessment of various functional properties of fixed macrophages. 58% of psoriatics who had no systemic drug treatment demonstrated peripheral extension of the bone marrow space indicating hyperplasia of bone marrow macrophages. This phenomenon could be observed only in one normal subject who was a high-performance sportsman. 83% (n=6) of psoriatics with cirrhosis of liver demonstrated bone marrow extension. The 'capacity' of bone marrow macrophages to engulf Tc-99m-HSA-MM ('uptake ratio') was diminished in 42% of non-treated as well as 66% of psoriatics treated with aromatic retinoid. The phagocytic and proteolytic turnover of Tc-99m-HSA-MM in bone marrow, spleen, and liver was found to be accelerated in 66% of non-treated psoriatics, normal, accelerated or delayed in psoriatics treated with aromatic retinoid as well as considerably delayed in all of the psoriatics with cirrhosis of liver. Functional bone marrow scintigraphy proved to be an appropriate in vivo test system to reveal abnormalities of fixed macrophages in psoriatics. Furthermore, theratpeutic effects as well as influences of pre-existing disorders on different macrophage populations can be assessed. (Author)

  15. Magnetic resonance imaging of the bone marrow

    Energy Technology Data Exchange (ETDEWEB)

    Baur-Melnyk, Andrea (ed.) [Klinikum der Univ. Muenchen (Germany). Inst. fuer Klinische Radiologie

    2013-08-01

    The first book devoted to MRI of the bone marrow. Describes the MRI appearances of normal bone marrows and the full range of bone marrow disorders. Discusses the role of advanced MRI techniques and contrast enhancement. On account of its unrivalled imaging capabilities and sensitivity, magnetic resonance imaging (MRI) is considered the modality of choice for the investigation of physiologic and pathologic processes affecting the bone marrow. This book describes the MRI appearances of both the normal bone marrow, including variants, and the full range of bone marrow disorders. Detailed discussion is devoted to malignancies, including multiple myeloma, lymphoma, chronic myeloproliferative disorders, leukemia, and bone metastases. Among the other conditions covered are benign and malignant compression fractures, osteonecrosis, hemolytic anemia, Gaucher's disease, bone marrow edema syndrome, trauma, and infective and non-infective inflammatory disease. Further chapters address the role of MRI in assessing treatment response, the use of contrast media, and advanced MRI techniques. Magnetic Resonance Imaging of the Bone Marrow represents an ideal reference for both novice and experienced practitioners.

  16. Clinical aspects of bone marrow transplantation

    International Nuclear Information System (INIS)

    Shmitts, N.; Gassmann, V.; Leffler, G.

    1986-01-01

    Experience of bone marrow transplantation into patients with myeloproliferative syndromes, myelodysplasias and highly malignant lymphomas is presented. Side early and late effects of transplantation are described. The frequency and severity of complications of bone marrow transplantation depend sufficiently on the disease as well as on patient's age and general condition

  17. [Endogenous pyrogen formation by bone marrow cells].

    Science.gov (United States)

    Efremov, O M; Sorokin, A V; El'kina, O A

    1978-01-01

    The cells of the rabbit bone marrow produced endogenous pyrogen in response to stimulation with bacterial lipopolysaccharide. Incubation of the cells in medium No 199 containing a 15% homologous serum is optimal for the release of pyrogen. It is supposed that the cells of the bone marrow take part in the formation of endgenous pyrogen and in the mechanism of pyrexia in the organism.

  18. Marrow uptake index (MUI): A quantitative scintigraphic study of bone marrow in aplastic anaemia

    International Nuclear Information System (INIS)

    Padhy, A.K.; Garg, A.; Kochupillai, V.; Gopinath, P.G.; Basu, A.K.

    1987-01-01

    Aplastic anaemia affects the entire bone marrow. This prospective study was undertaken to develop and standardise a new nuclear medicine technique called 'dynamic bone marrow imaging'. Eleven patients and ten controls were studied. Serial images of the pelvis were obtained in frame mode following intravenous injection of 185-370 mBq of 99m Tc S. Colloid, and an index, called the bone marrow uptake index was calculated by taking into consideration the time activity curve obtained over the iliac crest. This was followed by static imaging of the entire bone marrow in all cases. It was possible to obtain excellent information regarding topographic distribution of bone marrow as well as detect early changes in bone marrow function following treatment. An attempt was also made to correlate bone marrow cellularity as obtained by bone marrow biopsy with results of dynamic bone marrow scintigraphy. On the basis of the encouraging results obtained in the present study, the authors feel that dynamic bone marrow imaging is an excellent technique for the objective evaluation of bone marrow in aplastic anaemia. 20 refs.; 4 figs.; 5 tabs

  19. Treating fat grafts with human endothelial progenitor cells promotes their vascularization and improves their survival in diabetes mellitus.

    Science.gov (United States)

    Hamed, Saher; Ben-Nun, Ohad; Egozi, Dana; Keren, Aviad; Malyarova, Nastya; Kruchevsky, Danny; Gilhar, Amos; Ullmann, Yehuda

    2012-10-01

    Bone marrow-derived endothelial progenitor cells are required for vascularization of a fat graft to form a functional microvasculature within the graft and to facilitate its integration into the surrounding tissues. Organ transplantation carries a high risk of graft loss and rejection in patients with diabetes mellitus because endothelial progenitor cell function is impaired. The authors investigated the influence of endothelial progenitor cell treatment on the phenotype and survival of human fat grafts in immunocompromised mice with experimentally induced diabetes mellitus. The authors injected 1 ml of human fat tissue into the scalps of 14 nondiabetic and 28 diabetic immunocompromised mice, and then treated some of the grafts with endothelial progenitor cells that was isolated from the blood of a human donor. The phenotype of the endothelial progenitor cell-treated fat grafts from the 14 diabetic mice was compared with that of the untreated fat grafts from 14 nondiabetic and 14 diabetic mice, 18 days and 15 weeks after fat transplantation. Determination of graft phenotype included measurements of weight and volume, vascular endothelial growth factor levels, vascular endothelial growth factor receptor-2, endothelial nitric oxide synthase, and caspase 3 expression levels, and histologic analysis of the extent of vascularization. The untreated grafts from the diabetic mice were fully resorbed 15 weeks after fat transplantation. The phenotype of endothelial progenitor cell-treated fat grafts from the diabetic mice was similar to that of the untreated fat grafts from the nondiabetic mice. Endothelial progenitor cell treatment of transplanted fat can increase the survival of a fat graft by inducing its vascularization and decreasing the extent of apoptosis.

  20. Papillary endothelial hyperplasia in angiokeratoma.

    Science.gov (United States)

    Mehta, Anurag; Sayal, Satish Kumar; Raman, Deep Kumar; Sood, Aradhana

    2003-01-01

    Papillary endothelial hyperplasia (Masson's tumour) is a reactive proliferation of endothelium producing papillary structures with fibrovascular cores. Dilatation, stasis and accompanying inflammation have been incriminated as the inciting events, evident by the presence of this lesion in haemorrhoids, urethral caruncles and laryngeal polyps. We present here a case of papillary endothelial hyperplasia in angiokeratoma hitherto undescribed despite sharing common etiopathogenetic features of dilatation and stasis with other aforementioned lesions.

  1. Bone-Marrow Storage and Transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Costachel, O.; Corneci, I.; Andrian, T.; Kitzulescu, I.; Popescu, N.; Pascu, D.; Buzi, E.; Voiculetz, N. [Oncological Institute, Bucharest (Romania)

    1969-07-15

    The authors present some results from their experiments on bone-marrow storage and transplantation. The main problems with preservation of stored bone marrow are the duration, temperature, adjuvant substances and the significance of viability tests during the conservation processes. The results showed that: Bullet Storage of bone marrow at +4eC produces a progressive decrease in its restoring capacity versus storage time. Bullet While bone marrow stored for 24 h is able to restore 100% of dogs lethally irradiated with 600 rad, after 10 days of storage only 20% of the animals can be restored. Bullet No correlation exists between the actual survival of dogs and that calculated by dye exclusion tests, which indicate a rather high (70%) viability, even after 10 days bone-marrow storage at +4 Degree-Sign C. Bullet DNA degradation (depolymerization) measurements of the bone marrow may be used as a supplementary test for checking the viability or restoration potency of bone-marrow cells after storage. Bullet In the freezing process, the optimum contact time between glycerol and the bone-marrow cells is 15 min. Results of experiments regarding certain bone-marrow transplantation problems showed that: Bullet The best time to administer bone marrow is between 24 and 48 h after irradiation. Bullet No survivors were obtained with dogs lethally irradiated with 600 rad by administering autogenic or allogenic DNA extracted from bone marrow, spleen or liver. Bullet Histocompatibility related to sex may play an important role in the bone-marrow graft. The lowest survival of C57BL mice was obtained when the donors were males and the recipients females. Bullet In radioprotection with foetal haemocytopoietic tissues, the donor's age represents one of the main factors. The best results were obtained in experiments on rats, with 19- to 20-day foetal liver (period of complete and maximum haemocytopoietic activity). The tissues mentioned below may be connected with the appearance of

  2. Bone-Marrow Storage and Transplantation

    International Nuclear Information System (INIS)

    Costăchel, O.; Corneci, I.; Andrian, T.; Kitzulescu, I.; Popescu, N.; Pascu, D.; Buzi, E.; Voiculetz, N.

    1969-01-01

    The authors present some results from their experiments on bone-marrow storage and transplantation. The main problems with preservation of stored bone marrow are the duration, temperature, adjuvant substances and the significance of viability tests during the conservation processes. The results showed that: • Storage of bone marrow at +4eC produces a progressive decrease in its restoring capacity versus storage time. • While bone marrow stored for 24 h is able to restore 100% of dogs lethally irradiated with 600 rad, after 10 days of storage only 20% of the animals can be restored. • No correlation exists between the actual survival of dogs and that calculated by dye exclusion tests, which indicate a rather high (70%) viability, even after 10 days bone-marrow storage at +4°C. • DNA degradation (depolymerization) measurements of the bone marrow may be used as a supplementary test for checking the viability or restoration potency of bone-marrow cells after storage. • In the freezing process, the optimum contact time between glycerol and the bone-marrow cells is 15 min. Results of experiments regarding certain bone-marrow transplantation problems showed that: • The best time to administer bone marrow is between 24 and 48 h after irradiation. • No survivors were obtained with dogs lethally irradiated with 600 rad by administering autogenic or allogenic DNA extracted from bone marrow, spleen or liver. • Histocompatibility related to sex may play an important role in the bone-marrow graft. The lowest survival of C57BL mice was obtained when the donors were males and the recipients females. • In radioprotection with foetal haemocytopoietic tissues, the donor's age represents one of the main factors. The best results were obtained in experiments on rats, with 19- to 20-day foetal liver (period of complete and maximum haemocytopoietic activity). The tissues mentioned below may be connected with the appearance of certain typical signs of secondary syndrome

  3. MR imaging of bone marrow disorders

    International Nuclear Information System (INIS)

    Yoshida, H.; Mano, I.; Yashiro, N.; Asai, S.; Lio, M.

    1986-01-01

    The author performed MR imaging in 89 patients with bone marrow disorders (29 with aplastic anemia, 20 with leukemia, 9 with postirradiation changes, 8 with hemosiderosis, 6 with primary bone tumors and metastases, and 17 with bone marrow disorders of other etiologies). They selected the thoracic and lumbar vertebral marrow as a target and used both T1-weighted spin-echo images and calculated T1 images. T1 was prolonged in bone marrow hyperplasia but shortened in hypoplasia. Bone marrow T1 values proved to depend on the number of fat cells (pathologic correlation). In aplastic anemia scattered islands of low signal intensity were seen within a background of high signal intensity in some typical cases. MR imaging patterns were used for staging aplastic anemia. T1 was prolonged in leukemia cells

  4. Bacterial membrane activity of a-peptide/b-peptoid chimeras: Influence of amino acid composition and chain length on the activity against different bacterial strains

    DEFF Research Database (Denmark)

    Hein-Kristensen, Line; Knapp, Kolja M; Franzyk, Henrik

    2011-01-01

    and 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...... acid only had a minor effect on MIC values, whereas chain length had a profound influence on activity. All chimeras were less active against Serratia marcescens (MICs above 46 μM). The chimeras were bactericidal and induced leakage of ATP from Staphylococcus aureus and S. marcescens with similar time...... of onset and reduction in the number of viable cells. EDTA pre-treatment of S. marcescens and E. coli followed by treatment with chimeras resulted in pronounced killing indicating that disintegration of the Gram-negative outer membrane eliminated innate differences in susceptibility. Chimera chain length...

  5. Chimeras taking shape: Potential functions of proteins encoded by chimeric RNA transcripts

    Science.gov (United States)

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

    2012-01-01

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Using a periclinal chimera to unravel layer-specific gene expression in plants.

    Science.gov (United States)

    Filippis, Ioannis; Lopez-Cobollo, Rosa; Abbott, James; Butcher, Sarah; Bishop, Gerard J

    2013-09-01

    Plant organs are made from multiple cell types, and defining the expression level of a gene in any one cell or group of cells from a complex mixture is difficult. Dicotyledonous plants normally have three distinct layers of cells, L1, L2 and L3. Layer L1 is the single layer of cells making up the epidermis, layer L2 the single cell sub-epidermal layer and layer L3 constitutes the rest of the internal cells. Here we show how it is possible to harvest an organ and characterise the level of layer-specific expression by using a periclinal chimera that has its L1 layer from Solanum pennellii and its L2 and L3 layers from Solanum lycopersicum. This is possible by measuring the level of the frequency of species-specific transcripts. RNA-seq analysis enabled the genome-wide assessment of whether a gene is expressed in the L1 or L2/L3 layers. From 13 277 genes that are expressed in both the chimera and the parental lines and with at least one polymorphism between the parental alleles, we identified 382 genes that are preferentially expressed in L1 in contrast to 1159 genes in L2/L3. Gene ontology analysis shows that many genes preferentially expressed in L1 are involved in cutin and wax biosynthesis, whereas numerous genes that are preferentially expressed in L2/L3 tissue are associated with chloroplastic processes. These data indicate the use of such chimeras and provide detailed information on the level of layer-specific expression of genes. © 2013 East Malling Research The Plant Journal © 2013 John Wiley & Sons Ltd.

  8. Red-yellow marrow conversion: Its effect on the location of some solitary bone lesions

    International Nuclear Information System (INIS)

    Kricun, M.E.

    1985-01-01

    The location of red marrow related bone lesions is dependent upon the distribution of red marrow. It is altered by the normal conversion of red marrow to yellow (fat) marrow and by the reconversion of yellow marrow to red marrow caused by marrow infiltrating disorders or marrow stress disorders. (orig.)

  9. Self-organized emergence of multilayer structure and chimera states in dynamical networks with adaptive couplings

    Science.gov (United States)

    Kasatkin, D. V.; Yanchuk, S.; Schöll, E.; Nekorkin, V. I.

    2017-12-01

    We report the phenomenon of self-organized emergence of hierarchical multilayered structures and chimera states in dynamical networks with adaptive couplings. This process is characterized by a sequential formation of subnetworks (layers) of densely coupled elements, the size of which is ordered in a hierarchical way, and which are weakly coupled between each other. We show that the hierarchical structure causes the decoupling of the subnetworks. Each layer can exhibit either a two-cluster state, a periodic traveling wave, or an incoherent state, and these states can coexist on different scales of subnetwork sizes.

  10. Human iPSC Glial Mouse Chimeras Reveal Glial Contributions to Schizophrenia

    DEFF Research Database (Denmark)

    Windrem, Martha S.; Osipovitch, Mikhail; Liu, Zhengshan

    2017-01-01

    with childhood-onset SCZ. After neonatal implantation into myelin-deficient shiverer mice, SCZ GPCs showed premature migration into the cortex, leading to reduced white matter expansion and hypomyelination relative to controls. The SCZ glial chimeras also showed delayed astrocytic differentiation and abnormal...... astrocytic morphologies. When established in myelin wild-type hosts, SCZ glial mice showed reduced prepulse inhibition and abnormal behavior, including excessive anxiety, antisocial traits, and disturbed sleep. RNA-seq of cultured SCZ human glial progenitor cells (hGPCs) revealed disrupted glial...

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

    Science.gov (United States)

    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.

  12. Carnosol promotes endothelial differentiation under H2O2-induced oxidative stress

    Directory of Open Access Journals (Sweden)

    Ou Shulin

    2017-01-01

    Full Text Available Oxidative stress causes deregulation of endothelial cell differentiation. Carnosol is a potent antioxidant and antiinflammatory compound. In the present study, we examined whether the antioxidant effect of carnosol might protect bone marrow stem cells against H2O2-induced oxidative stress and promote endothelial differentiation. We examined cell viability by the MTT assay; oxidative stress and apoptosis were analyzed through changes in ROS levels, apoptotic ratio and caspase-3 activity; changes in protein expression of OCT-4, Flk-1, CD31 and Nrf-2 were assessed by Western blot analysis. H2O2 treatment increased oxidative stress and reduced cell viability, while the stem cell marker OCT-4 and endothelial markers Flk-1, CD31 were significantly downregulated as a result of the treatment with H2O2. Treatment with carnosol improved the antioxidant status, increased OCT-4 expression and promoted endothelial differentiation. This study provides evidence that carnosol could increase the antioxidant defense mechanism and promote endothelial differentiation.

  13. Contribution of endothelial progenitors and proangiogenic hematopoietic cells to vascularization of tumor and ischemic tissue

    Science.gov (United States)

    Kopp, Hans-Georg; Ramos, Carlos A.; Rafii, Shahin

    2010-01-01

    Purpose of review During the last several years, a substantial amount of evidence from animal as well as human studies has advanced our knowledge of how bone marrow derived cells contribute to neoangiogenesis. In the light of recent findings, we may have to redefine our thinking of endothelial cells as well as of perivascular mural cells. Recent findings Inflammatory hematopoietic cells, such as macrophages, have been shown to promote neoangiogenesis during tumor growth and wound healing. Dendritic cells, B lymphocytes, monocytes, and other immune cells have also been found to be recruited to neoangiogenic niches and to support neovessel formation. These findings have led to the concept that subsets of hematopoietic cells comprise proangiogenic cells that drive adult revascularization processes. While evidence of the importance of endothelial progenitor cells in adult vasculogenesis increased further, the role of these comobilized hematopoietic cells has been intensely studied in the last few years. Summary Angiogenic factors promote mobilization of vascular endothelial growth factor receptor 1-positive hematopoietic cells through matrix metalloproteinase-9 mediated release of soluble kit-ligand and recruit these proangiogenic cells to areas of hypoxia, where perivascular mural cells present stromal-derived factor 1 (CXCL-12) as an important retention signal. The same factors are possibly involved in mobilization of vascular endothelial growth factor receptor 2-positive endothelial precursors that may participate in neovessel formation. The complete characterization of mechanisms, mediators and signaling pathways involved in these processes will provide novel targets for both anti and proangiogenic therapeutic strategies. PMID:16567962

  14. Numerical and analytical investigation of the chimera state excitation conditions in the Kuramoto-Sakaguchi oscillator network

    Science.gov (United States)

    Frolov, Nikita S.; Goremyko, Mikhail V.; Makarov, Vladimir V.; Maksimenko, Vladimir A.; Hramov, Alexander E.

    2017-03-01

    In this paper we study the conditions of chimera states excitation in ensemble of non-locally coupled Kuramoto-Sakaguchi (KS) oscillators. In the framework of current research we analyze the dynamics of the homogeneous network containing identical oscillators. We show the chimera state formation process is sensitive to the parameters of coupling kernel and to the KS network initial state. To perform the analysis we have used the Ott-Antonsen (OA) ansatz to consider the behavior of infinitely large KS network.

  15. Artificial modulation of the gating behavior of a K+ channel in a KvAP-DNA chimera.

    Directory of Open Access Journals (Sweden)

    Andrew Wang

    Full Text Available We present experiments where the gating behavior of a voltage-gated ion channel is modulated by artificial ligand binding. We construct a channel-DNA chimera with the KvAP potassium channel reconstituted in an artificial membrane. The channel is functional and the single channel ion conductivity unperturbed by the presence of the DNA. However, the channel opening probability vs. bias voltage, i.e., the gating, can be shifted considerably by the electrostatic force between the charges on the DNA and the voltage sensing domain of the protein. Different hybridization states of the chimera DNA thus lead to different response curves of the channel.

  16. Analysis of the receptor-mediated B19V mechanism of internalization in the endothelial B19V infection and adenovirus-mediated reactivation of B19V in endothelial cells

    OpenAIRE

    Pozzuto, Tanja

    2012-01-01

    Human Parvovirus B19 (B19V) is the causative agent of erythema infectiosum, hydrops fetalis, aplastic crises and polyarthritis. B19V displays a very narrow cell and tissue tropism with productive infection thought to be restricted exclusively to erythroid progenitor cells in the bone marrow and fetal liver. However, over the last years increasing evidence for the presence of B19V DNA in other cell types and tissues such as synovial fibroblasts, tonsilles and skin as well as endothelial cells ...

  17. Exogenous endothelial cells as accelerators of hematopoietic reconstitution

    Directory of Open Access Journals (Sweden)

    Mizer J

    2012-11-01

    Full Text Available Abstract Despite the successes of recombinant hematopoietic-stimulatory factors at accelerating bone marrow reconstitution and shortening the neutropenic period post-transplantation, significant challenges remain such as cost, inability to reconstitute thrombocytic lineages, and lack of efficacy in conditions such as aplastic anemia. A possible means of accelerating hematopoietic reconstitution would be administration of cells capable of secreting hematopoietic growth factors. Advantages of this approach would include: a ability to regulate secretion of cytokines based on biological need; b long term, localized production of growth factors, alleviating need for systemic administration of factors that possess unintended adverse effects; and c potential to actively repair the hematopoietic stem cell niche. Here we overview the field of hematopoietic growth factors, discuss previous experiences with mesenchymal stem cells (MSC in accelerating hematopoiesis, and conclude by putting forth the rationale of utilizing exogenous endothelial cells as a novel cellular therapy for acceleration of hematopoietic recovery.

  18. Bone marrow transplantation after irradiation

    International Nuclear Information System (INIS)

    Koch, M.; Blaha, M.; Merka, V.

    1990-01-01

    Bone marrow transplantation after irradiation is successful in only a part of the affected patients. The Chernobyl accident added to our knowledge: BMT can save life after whole-body irradiation with a dose exceeding 7-8 Gy. A timely decision on transplantation after a nuclear accident is difficult to make (rapid determination of homogeneity and type of radiation and the total dose. HL-A typing in lymphopenia, precise identification of radiation damage to other target organs, etc.). Further attention is to be paid to the treatment. Transplantations in case of malignities (especially hematologic ones) and other diseases will add to our knowledge and will lead to more simple procedures. (author). 3 figs., 1 tab., 12 refs

  19. Haploinsufficiency of the insulin-like growth factor-1 receptor enhances endothelial repair and favorably modifies angiogenic progenitor cell phenotype.

    Science.gov (United States)

    Yuldasheva, Nadira Y; Rashid, Sheikh Tawqeer; Haywood, Natalie J; Cordell, Paul; Mughal, Romana; Viswambharan, Hema; Imrie, Helen; Sukumar, Piruthivi; Cubbon, Richard M; Aziz, Amir; Gage, Matthew; Mbonye, Kamatamu Amanda; Smith, Jessica; Galloway, Stacey; Skromna, Anna; Scott, D Julian A; Kearney, Mark T; Wheatcroft, Stephen B

    2014-09-01

    Defective endothelial regeneration predisposes to adverse arterial remodeling and is thought to contribute to cardiovascular disease in type 2 diabetes mellitus. We recently demonstrated that the type 1 insulin-like growth factor receptor (IGF1R) is a negative regulator of insulin sensitivity and nitric oxide bioavailability. In this report, we examined partial deletion of the IGF1R as a potential strategy to enhance endothelial repair. We assessed endothelial regeneration after wire injury in mice and abundance and function of angiogenic progenitor cells in mice with haploinsufficiency of the IGF1R (IGF1R(+/-)). Endothelial regeneration after arterial injury was accelerated in IGF1R(+/-) mice. Although the yield of angiogenic progenitor cells was lower in IGF1R(+/-) mice, these angiogenic progenitor cells displayed enhanced adhesion, increased secretion of insulin-like growth factor-1, and enhanced angiogenic capacity. To examine the relevance of IGF1R manipulation to cell-based therapy, we transfused IGF1R(+/-) bone marrow-derived CD117(+) cells into wild-type mice. IGF1R(+/-) cells accelerated endothelial regeneration after arterial injury compared with wild-type cells and did not alter atherosclerotic lesion formation. Haploinsufficiency of the IGF1R is associated with accelerated endothelial regeneration in vivo and enhanced tube forming and adhesive potential of angiogenic progenitor cells in vitro. Partial deletion of IGF1R in transfused bone marrow-derived CD117(+) cells enhanced their capacity to promote endothelial regeneration without altering atherosclerosis. Our data suggest that manipulation of the IGF1R could be exploited as novel therapeutic approach to enhance repair of the arterial wall after injury. © 2014 American Heart Association, Inc.

  20. Sustained apnea induces endothelial activation.

    Science.gov (United States)

    Eichhorn, Lars; Dolscheid-Pommerich, Ramona; Erdfelder, Felix; Ayub, Muhammad Ajmal; Schmitz, Theresa; Werner, Nikos; Jansen, Felix

    2017-09-01

    Apnea diving has gained worldwide popularity, even though the pathophysiological consequences of this challenging sport on the human body are poorly investigated and understood. This study aims to assess the influence of sustained apnea in healthy volunteers on circulating microparticles (MPs) and microRNAs (miRs), which are established biomarkers reflecting vascular function. Short intermittent hypoxia due to voluntary breath-holding affects circulating levels of endothelial cell-derived MPs (EMPs) and endothelial cell-derived miRs. Under dry laboratory conditions, 10 trained apneic divers performed maximal breath-hold. Venous blood samples were taken, once before and at 4 defined points in time after apnea. Samples were analyzed for circulating EMPs and endothelial miRs. Average apnea time was 329 seconds (±103), and SpO 2 at the end of apnea was 79% (±12). Apnea was associated with a time-dependent increase of circulating endothelial cell-derived EMPs and endothelial miRs. Levels of circulating EMPs in the bloodstream reached a peak 4 hours after the apnea period and returned to baseline levels after 24 hours. Circulating miR-126 levels were elevated at all time points after a single voluntary maximal apnea, whereas miR-26 levels were elevated significantly only after 30 minutes and 4 hours. Also miR-21 and miR-92 levels increased, but did not reach the level of significance. Even a single maximal breath-hold induces acute endothelial activation and should be performed with great caution by subjects with preexisting vascular diseases. Voluntary apnea might be used as a model to simulate changes in endothelial function caused by hypoxia in humans. © 2017 Wiley Periodicals, Inc.

  1. Bone Marrow Regeneration Promoted by Biophysically Sorted Osteoprogenitors From Mesenchymal Stromal Cells

    Science.gov (United States)

    Poon, Zhiyong; Lee, Wong Cheng; Guan, Guofeng; Nyan, Lin Myint; Lim, Chwee Teck; Han, Jongyoon

    2015-01-01

    Human tissue repair deficiencies can be supplemented through strategies to isolate, expand in vitro, and reimplant regenerative cells that supplant damaged cells or stimulate endogenous repair mechanisms. Bone marrow-derived mesenchymal stromal cells (MSCs), a subset of which is described as mesenchymal stem cells, are leading candidates for cell-mediated bone repair and wound healing, with hundreds of ongoing clinical trials worldwide. An outstanding key challenge for successful clinical translation of MSCs is the capacity to produce large quantities of cells in vitro with uniform and relevant therapeutic properties. By leveraging biophysical traits of MSC subpopulations and label-free microfluidic cell sorting, we hypothesized and experimentally verified that MSCs of large diameter within expanded MSC cultures were osteoprogenitors that exhibited significantly greater efficacy over other MSC subpopulations in bone marrow repair. Systemic administration of osteoprogenitor MSCs significantly improved survival rates (>80%) as compared with other MSC subpopulations (0%) for preclinical murine bone marrow injury models. Osteoprogenitor MSCs also exerted potent therapeutic effects as “cell factories” that secreted high levels of regenerative factors such as interleukin-6 (IL-6), interleukin-8 (IL-8), vascular endothelial growth factor A, bone morphogenetic protein 2, epidermal growth factor, fibroblast growth factor 1, and angiopoietin-1; this resulted in increased cell proliferation, vessel formation, and reduced apoptosis in bone marrow. This MSC subpopulation mediated rescue of damaged marrow tissue via restoration of the hematopoiesis-supporting stroma, as well as subsequent hematopoiesis. Together, the capabilities described herein for label-freeisolation of regenerative osteoprogenitor MSCs can markedly improve the efficacy of MSC-based therapies. PMID:25411477

  2. Bone marrow dosimetry for monoclonal antibody therapy

    International Nuclear Information System (INIS)

    Bigler, R.E.; Zanzonico, P.B.; Leonard, R.

    1986-01-01

    Immunoglobulins must permeate through the basement membrane of capillaries in order to enter the extracellular space (ECS) of tissue. Since the process is quite slow, the blood plasma activity in various organs contributes considerably to the radiation dose of the dose-limiting tissues. In bone marrow the basement membrane is absent and the blood circulation is functionally open. Therefore, blood plasma and marrow ECS maintain equal concentrations of labeled immunoglobulins. A combination of factors including intravenous administration, slow absorption into most tissues, slow breakdown and elimination of labeled immunoglobulin, and rapid entry into bone marrow ECS as well as known radiosensitivity of marrow led the authors to expect this tissue would prove to be the primary tissue at risk for systemic monoclonal antibody therapy. They have developed and applied in a Phase I clinical study of 131 I labeled CEA antibody a procedure for estimation of radiation dose to red bone marrow. Serieal measurements of blood plasma and total body retention are carried out. Binding of labeled antibody to the cellular components of blood is verified to be very low. They have observed bone marrow depression at doses greater than 400 rad. If no special procedures are used to reconstitute marrow after radiation treatment, this level represents a much greater than generally recognized limitation to radiolabeled monoclonal antibody therapy. 25 references, 4 tables

  3. STUDIES ON ENDOTHELIAL REACTIONS

    Science.gov (United States)

    Foot, Nathan Chandler

    1923-01-01

    operative. On the other hand, there may be an increase in the phagocytic activity of the endothelium of the sinusoids which might take up more bacteria under these changed conditions. Several investigators have claimed, recently, that there is an increased activity of the liver endothelium following splenectomy, their experiments being directed chiefly toward determining the fate of the erythrocytes. Pearce (1918) in reporting the effects of experimental splenectomy in dogs, states that there are definite compensatory changes in the lymph nodes, in the form of an increased proliferation of endothelial phagocytes, and that the stellate cells of the liver sinusoids often show a similar compensatory increase in number. In both cases the cells are, apparently, formed in situ rather than transported to the organs. He says: ‘Such findings suggest the development of a compensatory function on the part of the lymph-nodes and possibly the liver,’ and suggests that, in times of stress ‘the stellate cells of the liver thus assume, in part at least, the function of destroying red blood-corpuscles by phagocytosis.’ Incidentally, he presents an excellent discussion of the history and subject of splenectomy. Motohashi (1922) reports a great increase in the hemophagic power of the hepatic endothelium and an increase in the number of endothelial elements, after some 45 days following splenectomy in rabbits. Nishikawa and Takagi (1922) have observed similar phenomena with white rats, the Kupffer cells taking up erythrocytes in large numbers in splenectomized animals, whereas controls never show similar propensities on the part of these cells. It may be that different substances cause different reactions on the part of the hepatic endothelium. Contributory Experiment.—A side experiment was performed with five rabbits, two splenectomized and three controls, into which uniform doses of pneumococci were injected intravenously. They all died of septicemia after a few days. The results

  4. The Use of Endothelial Progenitor Cells for the Regeneration of Musculoskeletal and Neural Tissues

    Directory of Open Access Journals (Sweden)

    Naosuke Kamei

    2017-01-01

    Full Text Available Endothelial progenitor cells (EPCs derived from bone marrow and blood can differentiate into endothelial cells and promote neovascularization. In addition, EPCs are a promising cell source for the repair of various types of vascularized tissues and have been used in animal experiments and clinical trials for tissue repair. In this review, we focused on the kinetics of endogenous EPCs during tissue repair and the application of EPCs or stem cell populations containing EPCs for tissue regeneration in musculoskeletal and neural tissues including the bone, skeletal muscle, ligaments, spinal cord, and peripheral nerves. EPCs can be mobilized from bone marrow and recruited to injured tissue to contribute to neovascularization and tissue repair. In addition, EPCs or stem cell populations containing EPCs promote neovascularization and tissue repair through their differentiation to endothelial cells or tissue-specific cells, the upregulation of growth factors, and the induction and activation of endogenous stem cells. Human peripheral blood CD34(+ cells containing EPCs have been used in clinical trials of bone repair. Thus, EPCs are a promising cell source for the treatment of musculoskeletal and neural tissue injury.

  5. Endothelial jagged-2 sustains hematopoietic stem and progenitor reconstitution after myelosuppression.

    Science.gov (United States)

    Guo, Peipei; Poulos, Michael G; Palikuqi, Brisa; Badwe, Chaitanya R; Lis, Raphael; Kunar, Balvir; Ding, Bi-Sen; Rabbany, Sina Y; Shido, Koji; Butler, Jason M; Rafii, Shahin

    2017-12-01

    Angiocrine factors, such as Notch ligands, supplied by the specialized endothelial cells (ECs) within the bone marrow and splenic vascular niche play an essential role in modulating the physiology of adult hematopoietic stem and progenitor cells (HSPCs). However, the relative contribution of various Notch ligands, specifically jagged-2, to the homeostasis of HSPCs is unknown. Here, we show that under steady state, jagged-2 is differentially expressed in tissue-specific vascular beds, but its expression is induced in hematopoietic vascular niches after myelosuppressive injury. We used mice with EC-specific deletion of the gene encoding jagged-2 (Jag2) to demonstrate that while EC-derived jagged-2 was dispensable for maintaining the capacity of HSPCs to repopulate under steady-state conditions, by activating Notch2 it did contribute to the recovery of HSPCs in response to myelosuppressive conditions. Engraftment and/or expansion of HSPCs was dependent on the expression of endothelial-derived jagged-2 following myeloablation. Additionally, jagged-2 expressed in bone marrow ECs regulated HSPC cell cycle and quiescence during regeneration. Endothelial-deployed jagged-2 triggered Notch2/Hey1, while tempering Notch2/Hes1 signaling in HSPCs. Collectively, these data demonstrate that EC-derived jagged-2 activates Notch2 signaling in HSPCs to promote hematopoietic recovery and has potential as a therapeutic target to accelerate balanced hematopoietic reconstitution after myelosuppression.

  6. Pervasive transcription read-through promotes aberrant expression of oncogenes and RNA chimeras in renal carcinoma

    Science.gov (United States)

    Grosso, Ana R; Leite, Ana P; Carvalho, Sílvia; Matos, Mafalda R; Martins, Filipa B; Vítor, Alexandra C; Desterro, Joana MP; Carmo-Fonseca, Maria; de Almeida, Sérgio F

    2015-01-01

    Aberrant expression of cancer genes and non-canonical RNA species is a hallmark of cancer. However, the mechanisms driving such atypical gene expression programs are incompletely understood. Here, our transcriptional profiling of a cohort of 50 primary clear cell renal cell carcinoma (ccRCC) samples from The Cancer Genome Atlas (TCGA) reveals that transcription read-through beyond the termination site is a source of transcriptome diversity in cancer cells. Amongst the genes most frequently mutated in ccRCC, we identified SETD2 inactivation as a potent enhancer of transcription read-through. We further show that invasion of neighbouring genes and generation of RNA chimeras are functional outcomes of transcription read-through. We identified the BCL2 oncogene as one of such invaded genes and detected a novel chimera, the CTSC-RAB38, in 20% of ccRCC samples. Collectively, our data highlight a novel link between transcription read-through and aberrant expression of oncogenes and chimeric transcripts that is prevalent in cancer. DOI: http://dx.doi.org/10.7554/eLife.09214.001 PMID:26575290

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

    International Nuclear Information System (INIS)

    Sopuerta, Carlos F; Yunes, Nicolás

    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 geodesies. 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 geodesies, and harmonic coordinates, associated with the multipolar post-Minkowskian decomposition. The Chimera scheme is thus a combination of approximations that can be used to model generic inspirals of systems with extreme to intermediate mass ratios, and hence, it can provide valuable information for future space-based gravitational-wave observatories, like LISA, and even for advanced ground detectors. The local character in time of our multipolar post-Minkowskian self-force makes this scheme amenable to study the possible appearance of transient resonances in generic inspirals.

  8. Functional analysis of Kv1.2 and paddle chimera Kv channels in planar lipid bilayers

    Science.gov (United States)

    Tao, Xiao; MacKinnon, Roderick

    2010-01-01

    Summary Voltage-dependent K+ channels play key roles in shaping electrical signaling in both excitable as well as non-excitable cells. These channels open and close in response to the voltage changes across the cell membrane. Many studies have been carried out in order to understand the voltage sensing mechanism. Our laboratory recently determined the atomic structures of a mammalian voltage-dependent K+ channel Kv1.2 and a mutant of Kv1.2 named the ‘paddle-chimera’ channel, in which the voltage sensor paddle was transferred from Kv2.1 to Kv1.2. These two structures provide atomic descriptions of voltage-dependent channels with unprecedented clarity. Until now the functional integrity of these two channels biosynthesized in yeast cells have not been assessed. Here we report the electrophysiological and pharmacological properties of Kv1.2 and the paddle chimera channels in planar lipid bilayers. We demonstrate that Pichia yeast produce ‘normally functioning’ mammalian voltage-dependent K+ channels with qualitatively similar features to the Shaker K+ channel in the absence of the N-terminal inactivation gate, and that the paddle chimera mutant channel functions as well as Kv1.2. We find, however, that in several respects the Kv1.2 channel exhibits functional properties that are distinct from Kv1.2 channels reported in the literature. PMID:18638484

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

    International Nuclear Information System (INIS)

    Straume, T.; Raabe, O.G.; Walsh, K.J.; Wiley, L.M.

    1993-01-01

    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 137 Cs-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

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

    Science.gov (United States)

    Göttlicher, M; Widmark, E; Li, Q; 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 activators, we established a transcriptional transactivation assay by stably expressing in CHO cells a chimera of rat PPAR and the human glucocorticoid receptor that activates expression of the placental alkaline phosphatase reporter gene under the control of the mouse mammary tumor virus promoter. Testing of compounds related to lipid metabolism or peroxisomal proliferation revealed that 150 microM concentrations of arachidonic or linoleic acid but not of dehydroepiandrosterone, cholesterol, or 25-hydroxy-cholesterol, activate the receptor chimera. In addition, saturated fatty acids induce the reporter gene. Shortening the chain length to n = 6 or introduction of an omega-terminal carboxylic group abolished the activation potential of the fatty acid. In conclusion, the present results indicate that fatty acids can regulate gene expression mediated by a member of the steroid nuclear receptor superfamily. Images PMID:1316614

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

    Science.gov (United States)

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

    2016-04-28

    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.

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

    Science.gov (United States)

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

    2016-03-08

    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.

  13. Epidermis–dermis junction as a novel location for bone marrow-derived cells to reside in response to ionizing radiation

    International Nuclear Information System (INIS)

    Okano, Junko; Kojima, Hideto; Katagi, Miwako; Nakae, Yuki; Terashima, Tomoya; Nakagawa, Takahiko; Kurakane, Takeshi; Okamoto, Naoki; Morohashi, Keita; Maegawa, Hiroshi; Udagawa, Jun

    2015-01-01

    Bone marrow-derived cells (BMDCs) can migrate into the various organs in the mice irradiated by ionizing radiation (IR). However, it may not be the case in the skin. While IR is used for bone marrow (BM) transplantation, studying with the epidermal sheets demonstrated that the BMDC recruitment is extraordinarily rare in epidermis in the mouse. Herein, using the chimera mice with BM from green fluorescent protein (GFP) transgenic mice, we simply examined if BMDCs migrate into any layers in the total skin, as opposed to the epidermal sheets, in response to IR. Interestingly, we identified the presence of GFP-positive (GFP + ) cells in the epidermis-dermis junction in the total skin sections although the epidermal cell sheets failed to have any GFP cells. To examine a possibility that the cells in the junction could be mechanically dissociated during separating epidermal sheets, we then salvaged such dissociated cells and examined its characteristics. Surprisingly, some GFP + cells were found in the salvaged cells, indicating that these cells could be derived from BM. In addition, such BMDCs were also associated with inflammation in the junction. In conclusion, BMDCs can migrate to and reside in the epidermis-dermis junction after IR. - Highlights: • Bone marrow-derived cells (BMDCs) migrate in the epidermis due to ionizing radiation (IR). • BMDCs dissociate from the epidermis-dermis junction in preparing epidermal sheets. • The doses of IR determine the location and the number of migrating BMDCs in the skin

  14. Antilymphocytic antibodies and marrow transplantation. VIII. Recipient conditioning with Clq-affine monoclonal anti-pan T antibodies prevents GVHD in homozygous fully mismatched mice

    International Nuclear Information System (INIS)

    Thierfelder, S.; Kummer, U.; Schuh, R.; Mysliwietz, J.

    1986-01-01

    An approach to suppressing secondary disease with antibodies was studied that differed from conventional antibody treatment of donor marrow in vitro. It consisted of the selection of anti-Thy-1 antibodies with high affinity for Clq, the first subunit of the complement cascade, and a single injection of such antibodies into prospective irradiated marrow recipients. Monoclonal mouse IgM and rat IgG 2c antibodies of high titers in complement-dependent test systems but with low affinity for Clq caused little immunosuppression. Monoclonal rat IgG2b or mouse IgG2a anti-Thy-1 antibodies with high affinity for Clq prevented acute and chronic mortality of graft-v-host disease (GVHD), however, when injected in irradiated CBA or AKR mice prior to C57BL/6 spleen and/or bone marrow cell transfusion. This treatment simultaneously suppressed residual host-v-graft reactivity of the irradiated mice, so that permanent hematopoietic engraftment ensued even at 5 or 6 Gy. Full chimerism and specific tolerance were obtained. Primary immune response to SRBC was clearly depressed in the chimeras; secondary immune response was not. Clearance of T cell antibody activity (greater than 6 days), timing, and dose of injected antibody, as well as other modalities of the conditioning treatment that may have contributed to the remarkable immunosuppression, are discussed

  15. Epidermis–dermis junction as a novel location for bone marrow-derived cells to reside in response to ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Okano, Junko, E-mail: jokano@belle.shiga-med.ac.jp [Division of Anatomy and Cell Biology, Shiga University of Medical Science, Shiga (Japan); Kojima, Hideto; Katagi, Miwako [Department of Stem Cell Biology and Regenerative Medicine, Shiga University of Medical Science, Shiga (Japan); Nakae, Yuki [Department of Internal Medicine, Shiga University of Medical Science, Shiga (Japan); Terashima, Tomoya [Department of Stem Cell Biology and Regenerative Medicine, Shiga University of Medical Science, Shiga (Japan); Nakagawa, Takahiko [TMK Project, Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto (Japan); Kurakane, Takeshi; Okamoto, Naoki; Morohashi, Keita [Division of Anatomy and Cell Biology, Shiga University of Medical Science, Shiga (Japan); Maegawa, Hiroshi [Department of Internal Medicine, Shiga University of Medical Science, Shiga (Japan); Udagawa, Jun [Division of Anatomy and Cell Biology, Shiga University of Medical Science, Shiga (Japan)

    2015-06-12

    Bone marrow-derived cells (BMDCs) can migrate into the various organs in the mice irradiated by ionizing radiation (IR). However, it may not be the case in the skin. While IR is used for bone marrow (BM) transplantation, studying with the epidermal sheets demonstrated that the BMDC recruitment is extraordinarily rare in epidermis in the mouse. Herein, using the chimera mice with BM from green fluorescent protein (GFP) transgenic mice, we simply examined if BMDCs migrate into any layers in the total skin, as opposed to the epidermal sheets, in response to IR. Interestingly, we identified the presence of GFP-positive (GFP{sup +}) cells in the epidermis-dermis junction in the total skin sections although the epidermal cell sheets failed to have any GFP cells. To examine a possibility that the cells in the junction could be mechanically dissociated during separating epidermal sheets, we then salvaged such dissociated cells and examined its characteristics. Surprisingly, some GFP{sup +} cells were found in the salvaged cells, indicating that these cells could be derived from BM. In addition, such BMDCs were also associated with inflammation in the junction. In conclusion, BMDCs can migrate to and reside in the epidermis-dermis junction after IR. - Highlights: • Bone marrow-derived cells (BMDCs) migrate in the epidermis due to ionizing radiation (IR). • BMDCs dissociate from the epidermis-dermis junction in preparing epidermal sheets. • The doses of IR determine the location and the number of migrating BMDCs in the skin.

  16. Scavenger receptor-mediated endocytosis by sinusoidal cells in rat bone marrow

    International Nuclear Information System (INIS)

    Geoffroy, J.S.

    1987-01-01

    Endocytosis of serum albumin by sinusoidal endothelial cells in rat bone marrow was investigated initially at the ultrastructural level with subsequent biochemical investigation of the specificity mediating this event. Bovine serum albumin adsorbed to 20nm colloidal gold particles (AuBSA) was chosen as the electron microscopic probe. Morphological data strongly suggested that a receptor was involved in uptake of AuBSA. Confirmation of receptor involvement in the uptake of AuBSA by marrow sinusoidal endothelial cells was achieved utilizing an in situ isolated hind limb perfusion protocol in conjunction with unlabeled, radiolabeled, and radio-/colloidal gold labeled probes. The major findings of competition and saturation experiments were: (1) endocytosis of AuBSA was mediated by a receptor for modified/treated serum albumin; (2) endocytosis of formaldehyde-treated serum albumin was mediated by a binding site which may be the same or closely related to the site responsible for the uptake of AuBSA; and (3) endocytosis of native untreated albumin was not mediated by receptor and probably represents fluid-phase pinocitosis

  17. Bone marrow adipocytes promote the regeneration of stem cells and hematopoiesis by secreting SCF

    Science.gov (United States)

    Zhou, Bo O.; Yu, Hua; Yue, Rui; Zhao, Zhiyu; Rios, Jonathan J.; Naveiras, Olaia; Morrison, Sean J.

    2017-01-01

    Endothelial cells and Leptin Receptor+ (LepR+) stromal cells are critical sources of haematopoietic stem cell (HSC) niche factors, including Stem Cell Factor (SCF), in bone marrow. After irradiation or chemotherapy, these cells are depleted while adipocytes become abundant. We discovered that bone marrow adipocytes synthesize SCF. They arise from Adipoq-Cre/ER+ progenitors, which represent ~5% of LepR+ cells, and proliferate after irradiation. Scf deletion using Adipoq-Cre/ER inhibited hematopoietic regeneration after irradiation or 5-fluorouracil treatment, depleting HSCs and reducing mouse survival. Scf from LepR+ cells, but not endothelial, hematopoietic, or osteoblastic cells, also promoted regeneration. In non-irradiated mice, Scf deletion using Adipoq-Cre/ER did not affect HSC frequency in long bones, which have few adipocytes, but depleted HSCs in tail vertebrae, which have abundant adipocytes. A-ZIP/F1 ‘fatless” mice exhibited delayed hematopoietic regeneration in long bones but not in tail vertebrae, where adipocytes inhibited vascularization. Adipocytes are a niche component that promotes hematopoietic regeneration. PMID:28714970

  18. Bone marrow adipocytes promote the regeneration of stem cells and haematopoiesis by secreting SCF.

    Science.gov (United States)

    Zhou, Bo O; Yu, Hua; Yue, Rui; Zhao, Zhiyu; Rios, Jonathan J; Naveiras, Olaia; Morrison, Sean J

    2017-08-01

    Endothelial cells and leptin receptor + (LepR + ) stromal cells are critical sources of haematopoietic stem cell (HSC) niche factors, including stem cell factor (SCF), in bone marrow. After irradiation or chemotherapy, these cells are depleted while adipocytes become abundant. We discovered that bone marrow adipocytes synthesize SCF. They arise from Adipoq-Cre/ER + progenitors, which represent ∼5% of LepR + cells, and proliferate after irradiation. Scf deletion using Adipoq-Cre/ER inhibited haematopoietic regeneration after irradiation or 5-fluorouracil treatment, depleting HSCs and reducing mouse survival. Scf from LepR + cells, but not endothelial, haematopoietic or osteoblastic cells, also promoted regeneration. In non-irradiated mice, Scf deletion using Adipoq-Cre/ER did not affect HSC frequency in long bones, which have few adipocytes, but depleted HSCs in tail vertebrae, which have abundant adipocytes. A-ZIP/F1 'fatless' mice exhibited delayed haematopoietic regeneration in long bones but not in tail vertebrae, where adipocytes inhibited vascularization. Adipocytes are a niche component that promotes haematopoietic regeneration.

  19. Analyzing the cellular contribution of bone marrow to fracture healing using bone marrow transplantation in mice

    International Nuclear Information System (INIS)

    Colnot, C.; Huang, S.; Helms, J.

    2006-01-01

    The bone marrow is believed to play important roles during fracture healing such as providing progenitor cells for inflammation, matrix remodeling, and cartilage and bone formation. Given the complex nature of bone repair, it remains difficult to distinguish the contributions of various cell types. Here we describe a mouse model based on bone marrow transplantation and genetic labeling to track cells originating from bone marrow during fracture healing. Following lethal irradiation and engraftment of bone marrow expressing the LacZ transgene constitutively, wild type mice underwent tibial fracture. Donor bone marrow-derived cells, which originated from the hematopoietic compartment, did not participate in the chondrogenic and osteogenic lineages during fracture healing. Instead, the donor bone marrow contributed to inflammatory and bone resorbing cells. This model can be exploited in the future to investigate the role of inflammation and matrix remodeling during bone repair, independent from osteogenesis and chondrogenesis

  20. Irradiation of the red bone marrow and the health implications ...

    African Journals Online (AJOL)

    The physiology and function of the bone is looked at as to the role in housing bone marrow. The bone marrow and particularly the red bone marrow is discussed. Sources of radiation are discussed and the health implications highlighted for caution and for study or evaluation. Key Words: Bone marrow, Irradiation, Radiation, ...

  1. DC8 and DC13 var genes associated with severe malaria bind avidly to diverse endothelial cells.

    Directory of Open Access Journals (Sweden)

    Marion Avril

    Full Text Available During blood stage infection, Plasmodium falciparum infected erythrocytes (IE bind to host blood vessels. This virulence determinant enables parasites to evade spleen-dependent killing mechanisms, but paradoxically in some cases may reduce parasite fitness by killing the host. Adhesion of infected erythrocytes is mediated by P. falciparum erythrocyte membrane protein 1 (PfEMP1, a family of polymorphic adhesion proteins encoded by var genes. Whereas cerebral binding and severe malaria are associated with parasites expressing DC8 and DC13 var genes, relatively little is known about the non-brain endothelial selection on severe malaria adhesive types. In this study, we selected P. falciparum-IEs on diverse endothelial cell types and demonstrate that DC8 and DC13 var genes were consistently among the major var transcripts selected on non-brain endothelial cells (lung, heart, bone marrow. To investigate the molecular basis for this avid endothelial binding activity, recombinant proteins were expressed from the predominant upregulated DC8 transcript, IT4var19. In-depth binding comparisons revealed that multiple extracellular domains from this protein bound brain and non-brain endothelial cells, and individual domains largely did not discriminate between different endothelial cell types. Additionally, we found that recombinant DC8 and DC13 CIDR1 domains exhibited a widespread endothelial binding activity and could compete for DC8-IE binding to brain endothelial cells, suggesting they may bind the same host receptor. Our findings provide new insights into the interaction of severe malaria adhesive types and host blood vessels and support the hypothesis that parasites causing severe malaria express PfEMP1 variants with a superior ability to adhere to diverse endothelial cell types, and may therefore endow these parasites with a growth and transmission advantage.

  2. The endothelial border to health

    DEFF Research Database (Denmark)

    Hansen, Nina Wærling; Hansen, Anker Jon; Sams, Anette

    2017-01-01

    player for maintenance of health and for development of a number of diseases. Endothelial dysfunction is known to be an important component of type 2 diabetes, but is also assumed to be involved in many other diseases, for example, rheumatoid arthritis, inflammatory bowel disease, asthma...... extracellular proteins form epitopes for potential specific antibody formation upon interactions with reducing sugars. This paper reviews the endothelial metabolism, biology, inflammatory processes, physical barrier functions, and summarizes evidence that although stochastic in nature, endothelial responses...... to hyperglycemia are major contributors to disease pathophysiology. We present molecular and mechanistic evidence that both biological and physical barriers, protein function, specific immunity, and inflammatory processes are compromised by hyperglycemic events and thus, hyperglycemic events alone should...

  3. The ChimERA project: Coupling mechanistic exposure and effect models into an integrated platform for ecological risk assessment

    NARCIS (Netherlands)

    Laender, de F.; Brink, van den P.J.; Janssen, C.R.; Guardo, Di A.

    2014-01-01

    Current techniques for the ecological risk assessment of chemical substances are often criticised for their lack of environmental realism, ecological relevance and methodological accuracy. ChimERA is a 3-year project (2013-2016), funded by Cefic's Long Range Initiative (LRI) that aims to address

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    . This 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 area...

  5. What Is a Bone Marrow Transplant?

    Science.gov (United States)

    ... however you can Daughter's dying wish became mother's motivation Be The Match Blog Stories Anna, transplant recipient ... Copyright © 1996-2018 National Marrow Donor Program. All Rights Reserved.

  6. Using quantitative real-time PCR to detect chimeras in transgenic tobacco and apricot and to monitor their dissociation

    Directory of Open Access Journals (Sweden)

    Burgos Lorenzo

    2010-07-01

    Full Text Available Abstract Background The routine generation of transgenic plants involves analysis of transgene integration into the host genome by means of Southern blotting. However, this technique cannot distinguish between uniformly transformed tissues and the presence of a mixture of transgenic and non-transgenic cells in the same tissue. On the other hand, the use of reporter genes often fails to accurately detect chimerical tissues because their expression can be affected by several factors, including gene silencing and plant development. So, new approaches based on the quantification of the amount of the transgene are needed urgently. Results We show here that chimeras are a very frequent phenomenon observed after regenerating transgenic plants. Spatial and temporal analyses of transformed tobacco and apricot plants with a quantitative, real-time PCR amplification of the neomycin phosphotransferase (nptII transgene as well as of an internal control (β-actin, used to normalise the amount of target DNA at each reaction, allowed detection of chimeras at unexpected rates. The amount of the nptII transgene differed greatly along with the sub-cultivation period of these plants and was dependent on the localisation of the analysed leaves; being higher in roots and basal leaves, while in the apical leaves it remained at lower levels. These data demonstrate that, unlike the use of the gus marker gene, real-time PCR is a powerful tool for detection of chimeras. Although some authors have proposed a consistent, positive Southern analysis as an alternative methodology for monitoring the dissociation of chimeras, our data show that it does not provide enough proof of uniform transformation. In this work, however, real-time PCR was applied successfully to monitor the dissociation of chimeras in tobacco plants and apricot callus. Conclusions We have developed a rapid and reliable method to detect and estimate the level of chimeras in transgenic tobacco and apricot

  7. Paracrine effects and heterogeneity of marrow-derived stem/progenitor cells: relevance for the treatment of respiratory diseases.

    Science.gov (United States)

    Conese, Massimo; Carbone, Annalucia; Castellani, Stefano; Di Gioia, Sante

    2013-01-01

    Stem cell-based treatment may represent a hope for the treatment of acute lung injury and pulmonary fibrosis, and other chronic lung diseases, such as cystic fibrosis, asthma and chronic obstructive pulmonary disease (COPD). It is well established in preclinical models that bone marrow-derived stem and progenitor cells exert beneficial effects on inflammation, immune responses and repairing of damage in virtually all lung-borne diseases. While it was initially thought that the positive outcome was due to a direct engraftment of these cells into the lung as endothelial and epithelial cells, paracrine factors are now considered the main mechanism through which stem and progenitor cells exert their therapeutic effect. This knowledge has led to the clinical use of marrow cells in pulmonary hypertension with endothelial progenitor cells (EPCs) and in COPD with mesenchymal stromal (stem) cells (MSCs). Bone marrow-derived stem cells, including hematopoietic stem/progenitor cells, MSCs, EPCs and fibrocytes, encompass a wide array of cell subsets with different capacities of engraftment and injured tissue-regenerating potential. The characterization/isolation of the stem cell subpopulations represents a major challenge to improve the efficacy of transplantation protocols used in regenerative medicine and applied to lung disorders. Copyright © 2013 S. Karger AG, Basel.

  8. Bone marrow lesions: A systematic diagnostic approach

    International Nuclear Information System (INIS)

    Grande, Filippo Del; Farahani, Sahar J; Carrino, John A; Chhabra, Avneesh

    2014-01-01

    Bone marrow lesions on magnetic resonance (MR) imaging are common and may be seen with various pathologies. The authors outline a systematic diagnostic approach with proposed categorization of various etiologies of bone marrow lesions. Utilization of typical imaging features on conventional MR imaging techniques and other problem-solving techniques, such as chemical shift imaging and diffusion-weighted imaging (DWI), to achieve accurate final diagnosis has been highlighted

  9. Thalassemia paravertebral tumors and bone marrow scan

    International Nuclear Information System (INIS)

    Huglo, D.; Rose, C.; Deveaux, M.; Bauters, F.; Marchandise, X.

    1995-01-01

    Two first cousins with thalassemia and with a paravertebral mass had had an indium 111 chloride bone marrow scan. Result of scan influenced therapy: medical treatment in one case where an extramedullary erythropoiesis was confirmed, surgical treatment in the other case. The use of dual-isotope SPECT (indium 111 chloride, HDP -99 Tc) constitutes a contribution to the establishment of diagnosis of extramedullary erythropoiesis, giving to bone marrow scintigraphy a merited importance, avoiding the biopsy. (authors). 15 refs., 5 figs

  10. Bone marrow lesions: A systematic diagnostic approach

    Directory of Open Access Journals (Sweden)

    Filippo Del Grande

    2014-01-01

    Full Text Available Bone marrow lesions on magnetic resonance (MR imaging are common and may be seen with various pathologies. The authors outline a systematic diagnostic approach with proposed categorization of various etiologies of bone marrow lesions. Utilization of typical imaging features on conventional MR imaging techniques and other problem-solving techniques, such as chemical shift imaging and diffusion-weighted imaging (DWI, to achieve accurate final diagnosis has been highlighted.

  11. BONE MARROW ABONRMALITIES IN HIV INFECTION

    OpenAIRE

    Sharad Antiram Dhurve

    2013-01-01

    Introduction Hematological abnormalities are a common complication of HIV infection. Bone marrow abnormalities occur in all stages of HIV infection. Present work was carried out to study the bone marrow abnormalities in patients with HIV/AIDS. Methods 160 patients of HIV +ve were included in the study. A complete blood count, relevant biochemical investigations, CD4 counts were done, besides a thorough history and clinical examination. HIV positive patients were classified as those having AID...

  12. Reintegration after bone marrow transplantation.

    Science.gov (United States)

    Baker, F; Zabora, J; Polland, A; Wingard, J

    1999-01-01

    This study examines the problems of bone marrow transplantation (BMT) survivors in returning to "normal" life in the community after BMT. Before being released from The Johns Hopkins Oncology Center, 84 recipients of BMT were interviewed regarding their quality of life and psychosocial adaptation. Survivors were reinterviewed at 6 months, and at 1 year post-BMT, producing considerable qualitative data regarding their problems in living. Eighty-four patients who had received BMT completed qualitative interviews and standardized measures before treatment, before the return home, and at 6 and 12 months post-BMT. The interviews were subjected to a content analysis methodology to establish units and categories to examine the body of material. Content analysis of these interviews from the first year after BMT identified three areas of psychosocial morbidity; 1) physical problems, which included fatigue, appearance, troubles in eating, and physical restrictions; 2) psychological problems, which included fears about the future, sense of loss of control, anxiety, and depression; and 3) community reintegration problems, which included difficulty in returning to former social roles, separation from home, family, and friends, difficulty in resuming social relations, dealing with stigmatization, problems with family and children, and financial and employment difficulties. Identification of these problems for BMT survivors can be used to guide the development of specific materials and services to prepare recipients of BMTs and their families for life after the transplant. These qualitative results can also be used to direct the development of assessment tools to identify potential patient and family problems.

  13. Characterization of the bone marrow adipocyte niche with three-dimensional electron microscopy.

    Science.gov (United States)

    Robles, Hero; Park, SungJae; Joens, Matthew S; Fitzpatrick, James A J; Craft, Clarissa S; Scheller, Erica L

    2018-01-27

    Unlike white and brown adipose tissues, the bone marrow adipocyte (BMA) exists in a microenvironment containing unique populations of hematopoietic and skeletal cells. To study this microenvironment at the sub-cellular level, we performed a three-dimensional analysis of the ultrastructure of the BMA niche with focused ion beam scanning electron microscopy (FIB-SEM). This revealed that BMAs display hallmarks of metabolically active cells including polarized lipid deposits, a dense mitochondrial network, and areas of endoplasmic reticulum. The distinct orientations of the triacylglycerol droplets suggest that fatty acids are taken up and/or released in three key areas - at the endothelial interface, into the hematopoietic milieu, and at the bone surface. Near the sinusoidal vasculature, endothelial cells send finger-like projections into the surface of the BMA which terminate near regions of lipid within the BMA cytoplasm. In some regions, perivascular cells encase the BMA with their flattened cellular projections, limiting contacts with other cells in the niche. In the hematopoietic milieu, BMAT adipocytes of the proximal tibia interact extensively with maturing cells of the myeloid/granulocyte lineage. Associations with erythroblast islands are also prominent. At the bone surface, the BMA extends organelle and lipid-rich cytoplasmic regions toward areas of active osteoblasts. This suggests that the BMA may serve to partition nutrient utilization between diverse cellular compartments, serving as an energy-rich hub of the stromal-reticular network. Lastly, though immuno-EM, we've identified a subset of bone marrow adipocytes that are innervated by the sympathetic nervous system, providing an additional mechanism for regulation of the BMA. In summary, this work reveals that the bone marrow adipocyte is a dynamic cell with substantial capacity for interactions with the diverse components of its surrounding microenvironment. These local interactions likely contribute to

  14. Phenotypic characterization of the bone marrow stem cells used in regenerative cellular therapy

    International Nuclear Information System (INIS)

    Macias Abraham, Consuelo; Valle Perez, Lazaro O del; Baganet Cobas, Aymara

    2011-01-01

    Regenerative medicine is a novel therapeutic method with broad potential for the treatment of various illnesses, based on the use of bone marrow (BM) stem cells, whose phenotypic characterization is limited. The paper deals with the expression of different cell membrane markers in mononuclear BM cells from 14 patients who underwent autologous cell therapy, obtained by medullary puncture and mobilization to peripheral blood, with the purpose of characterizing the different types of cells present in that heterogeneous cellular population and identifying the adhesion molecules involved in their adhesion. A greater presence was observed of adherent stem cells from the marrow stroma in mononuclear cells obtained directly from the BM; a larger population of CD90 +c ells in mononuclear cells from CD34 -/ CD45 -p eripheral blood with a high expression of molecules CD44 and CD62L, which suggests a greater presence of mesenchymal stem cells (MSC) in mobilized cells from the marrow stroma. The higher levels of CD34 +c ells in peripheral blood stem cells with a low expression of molecules CD117 -a nd DR -s uggests the presence of hematopoietic stem cells, hemangioblasts and progenitor endothelial cells mobilized to peripheral circulation. It was found that mononuclear cells from both the BM and peripheral blood show a high presence of stem cells with expression of adhesion molecule CD44 (MMC marker), probably involved in their migration, settling and differentiation

  15. Safety assessment of bone marrow derived MSC grown in platelet-rich plasma

    Directory of Open Access Journals (Sweden)

    Shoji Fukuda

    2015-06-01

    Full Text Available The injection of endothelial progenitor cells and mononuclear cells derived from bone marrow at the ischemic region of peripheral artery disease patients is reported to be effective for therapeutic angiogenesis; however, these cell therapies require large amounts of bone marrow to obtain sufficient numbers of cells. To solve this problem, we attempted to culture bone-marrow-derived mesenchymal stem cells (BM-MSC, which are supposed to secrete several cytokines that promote angiogenesis. We also focused on using platelet-rich plasma (PRP as a supplement for cell culture instead of fetal bovine serum. Human BM-MSC obtained from healthy volunteers expanded rapidly when cultured with 10% PRP prepared from their own blood. FACS analysis revealed that these cultured human MSC were homogeneous populations, and chromosomal analysis showed a normal karyotype. Moreover, the angiogenetic effect was apparent two weeks after human BM-MSC were injected into the ischemic muscle in SCID mice. Tumor formation was not detected three months after injection into SCID mice either subcutaneously or intramuscularly. To simulate clinical settings, canine BM-MSC were grown with canine PRP and injected into their ischemic muscles. We confirmed that donor cells existed in situ two and six weeks after operation without any side effects. These results suggest that cultured human BM-MSC can be a promising cell source for therapeutic angiogenesis.

  16. Endothelial Progenitor Cell Dysfunction in Polycystic Ovary Syndrome: Implications for The Genesis of Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Yu-Hsun Kao

    2013-01-01

    Full Text Available Polycystic ovary syndrome (PCOS, the most common endocrine disorder affecting women ofreproductive age, is characterized by hyperandrogenism and insulin resistance. Women withPCOS have a higher risk for cardiovascular diseases (CVDs and endothelial dysfunction. Themechanisms underlying these risks are unclear. Human peripheral blood contains circulatingendothelial progenitor cells (EPCs derived from bone marrow that have the ability to proliferate anddifferentiate into mature endothelial cells, which may contribute to vessel homeostasis and repair.PCOS is associated with insulin resistance, hyperinsulinemia, and dyslipidemia, which may resultin EPC dysfunction. In this review, we summarize the potential mechanisms of EPC dysfunction inPCOS, which possibly result in a higher genesis of CVDs in PCOS-affected subjects.

  17. Evaluation of velvet antler total protein effect on bone marrow-derived endothelial progenitor cells

    OpenAIRE

    Xiao, Xiang; Li, Lin; Xu, Shuqiang; Mao, Min; Pan, Ruiyan; Li, Yanjun; Wu, Jiayun; Huang, Li; Zheng, Xiaoyun

    2017-01-01

    Lu Rong, velvet antler (VA), is a traditional Chinese medicine, which is used as a food supplement and therapeutic drug in China, Japan, Russia, New Zealand and Southeast Asia. The regenerative characteristics of VA have resulted in great research interest, particularly regarding the fields of organ grafting and stem cell differentiation. Various VA proteomic studies verified that proteins act as the primary bioactive components of VA. The present study aimed to investigate if VA proteins (VA...

  18. Endothelial dysfunction after non-cardiac surgery

    DEFF Research Database (Denmark)

    Søndergaard, E S; Fonnes, S; Gögenur, I

    2015-01-01

    was to systematically review the literature to evaluate the association between non-cardiac surgery and non-invasive markers of endothelial function. METHODS: A systematic search was conducted in MEDLINE, EMBASE and Cochrane Library Database according to the PRISMA guidelines. Endothelial dysfunction was described only...... transplantation and vascular surgery respectively) had an improvement in endothelial dysfunction 1 month after surgery. CONCLUSION: Endothelial function changes in relation to surgery. Assessment of endothelial function by non-invasive measures has the potential to guide clinicians in the prevention or treatment...

  19. Crystal structures of a GABAA-receptor chimera reveal new endogenous neurosteroid-binding sites.

    Science.gov (United States)

    Laverty, Duncan; Thomas, Philip; Field, Martin; Andersen, Ole J; Gold, Matthew G; Biggin, Philip C; Gielen, Marc; Smart, Trevor G

    2017-11-01

    γ-Aminobutyric acid receptors (GABA A Rs) are vital for controlling excitability in the brain. This is emphasized by the numerous neuropsychiatric disorders that result from receptor dysfunction. A critical component of most native GABA A Rs is the α subunit. Its transmembrane domain is the target for many modulators, including endogenous brain neurosteroids that impact anxiety, stress and depression, and for therapeutic drugs, such as general anesthetics. Understanding the basis for the modulation of GABA A R function requires high-resolution structures. Here we present the first atomic structures of a GABA A R chimera at 2.8-Å resolution, including those bound with potentiating and inhibitory neurosteroids. These structures define new allosteric binding sites for these modulators that are associated with the α-subunit transmembrane domain. Our findings will enable the exploitation of neurosteroids for therapeutic drug design to regulate GABA A Rs in neurological disorders.

  20. 2D and 3D core-collapse supernovae simulation results obtained with the CHIMERA code

    Energy Technology Data Exchange (ETDEWEB)

    Bruenn, S W; Marronetti, P; Dirk, C J [Physics Department, Florida Atlantic University, 777 W. Glades Road, Boca Raton, FL 33431-0991 (United States); Mezzacappa, A; Hix, W R [Physics Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831-6354 (United States); Blondin, J M [Department of Physics, North Carolina State University, Raleigh, NC 27695-8202 (United States); Messer, O E B [Center for Computational Sciences, Oak Ridge National Laboratory, Oak Ridge, TN 37831-6354 (United States); Yoshida, S, E-mail: bruenn@fau.ed [Max-Planck-Institut fur Gravitationsphysik, Albert Einstein Institut, Golm (Germany)

    2009-07-01

    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 M{sub o-dot} 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 M{sub o-dot} progenitor.

  1. Novel type of chimera spiral waves arising from decoupling of a diffusible component

    Energy Technology Data Exchange (ETDEWEB)

    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.

  2. CHIMERA II - A real-time multiprocessing environment for sensor-based robot control

    Science.gov (United States)

    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.

  3. Test of GET Electronics for the CHIMERA and FARCOS multi-detectors

    Science.gov (United States)

    De Luca, S.; Acosta, L.; Auditore, L.; Boiano, C.; Cardella, G.; Castoldi, A.; D'Andrea, M.; De Filippo, E.; Dell'Aquila, D.; Fichera, F.; Gnoffo, B.; Guazzoni, C.; Lanzalone, G.; Lombardo, I.; Martorana, N. S.; Minniti, T.; Norella, S.; Pagano, A.; Pagano, E. V.; Papa, M.; Pirrone, S.; Politi, G.; Quattrocchi, L.; Rizzo, F.; Russotto, P.; Saccà, G.; Trifirò, A.; Trimarchi, M.; Verde, G.; Vigilante, M.

    2017-11-01

    In this paper we present the results of the tests on the new digital electronics GET (General Electronics for Tpc), which will be used for the readout of the CsI(Tl) detectors of CHIMERA (Charged Heavy Ion Mass and Energy Resolving Array) and for the new correlator FARCOS (Femtoscope ARray for COrrelations and Spectroscopy). The new electronics allows us to digitize the full waveform of the signals produced by the detector. Among its features it is worth noticing the compactness and low power consumption (5W for 256 channels). Tests have been performed with pulsers, radioactive sources and ion beams. With such electronics very good results in energy resolution and isotope separation of the detected fragments were obtained, by using both hardware and software filters.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Development of a large scale Chimera grid system for the Space Shuttle Launch Vehicle

    Science.gov (United States)

    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.

  6. Chimera and modulated drift states in a ring of nonlocally coupled oscillators with heterogeneous phase lags

    Science.gov (United States)

    Choe, Chol-Ung; Kim, Ryong-Son; Ri, Ji-Song

    2017-09-01

    We consider a ring of phase oscillators with nonlocal coupling strength and heterogeneous phase lags. We analyze the effects of heterogeneity in the phase lags on the existence and stability of a variety of steady states. A nonlocal coupling with heterogeneous phase lags that allows the system to be solved analytically is suggested and the stability of solutions along the Ott-Antonsen invariant manifold is explored. We present a complete bifurcation diagram for stationary patterns including the uniform drift and modulated drift states as well as chimera state, which reveals that the stable modulated drift state and a continuum of metastable drift states could occur due to the heterogeneity of the phase lags. We verify our theoretical results using the direct numerical simulations of the model system.

  7. Chimera distribution amplitudes for the pion and the longitudinally polarized ρ-meson

    Energy Technology Data Exchange (ETDEWEB)

    Stefanis, N.G., E-mail: stefanis@tp2.ruhr-uni-bochum.de [Institut für Theoretische Physik II, Ruhr-Universität Bochum, D-44780 Bochum (Germany); Pimikov, A.V., E-mail: pimikov@theor.jinr.ru [Bogoliubov Laboratory of Theoretical Physics, JINR, 141980 Dubna (Russian Federation); Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000 (China)

    2016-01-15

    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.

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

    Science.gov (United States)

    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. Copyright © 2016 Institute of Psychoanalysis.

  9. Mouse lung contains endothelial progenitors with high capacity to form blood and lymphatic vessels

    Directory of Open Access Journals (Sweden)

    Barleon Bernhard

    2010-07-01

    Full Text Available Abstract Background Postnatal endothelial progenitor cells (EPCs have been successfully isolated from whole bone marrow, blood and the walls of conduit vessels. They can, therefore, be classified into circulating and resident progenitor cells. The differentiation capacity of resident lung endothelial progenitor cells from mouse has not been evaluated. Results In an attempt to isolate differentiated mature endothelial cells from mouse lung we found that the lung contains EPCs with a high vasculogenic capacity and capability of de novo vasculogenesis for blood and lymph vessels. Mouse lung microvascular endothelial cells (MLMVECs were isolated by selection of CD31+ cells. Whereas the majority of the CD31+ cells did not divide, some scattered cells started to proliferate giving rise to large colonies (> 3000 cells/colony. These highly dividing cells possess the capacity to integrate into various types of vessels including blood and lymph vessels unveiling the existence of local microvascular endothelial progenitor cells (LMEPCs in adult mouse lung. EPCs could be amplified > passage 30 and still expressed panendothelial markers as well as the progenitor cell antigens, but not antigens for immune cells and hematopoietic stem cells. A high percentage of these cells are also positive for Lyve1, Prox1, podoplanin and VEGFR-3 indicating that a considerabe fraction of the cells are committed to develop lymphatic endothelium. Clonogenic highly proliferating cells from limiting dilution assays were also bipotent. Combined in vitro and in vivo spheroid and matrigel assays revealed that these EPCs exhibit vasculogenic capacity by forming functional blood and lymph vessels. Conclusion The lung contains large numbers of EPCs that display commitment for both types of vessels, suggesting that lung blood and lymphatic endothelial cells are derived from a single progenitor cell.

  10. Magnetic resonance imaging of bone marrow disease in children

    International Nuclear Information System (INIS)

    Cohen, M.D.; Klatte, E.C.; Baehner, R.

    1984-01-01

    Seven children underwent magnetic resonance imaging (MRI) of the bone marrow: results showed that it is technically feasible to obtain good MR images of marrow in children. MR has detected abnormality in the bone marrow of a child who had metastatic neuroblastoma. The extent of abnormality in the femur correlated well with findings of a bone marrow isotope scan. In one child who had idiopathic aplastic anemia, diseased marrow could not be distinguished from normal marrow on MR images. MRI identified abnormality of the marrow in osteogenic sarcoma, and demonstrated change in response to chemotherapy. It displayed marrow spread of tumors as well as CT. MRI showed marrow abnormality in four children who had leukemia

  11. Autoantibody detection in type 2 autoimmune hepatitis using a chimera recombinant protein.

    Science.gov (United States)

    Vitozzi, Susana; Lapierre, Pascal; Djilali-Saiah, Idriss; Alvarez, Fernando

    2002-04-01

    Autoantibodies against cytochrome P450 2D6 (CYP2D6), known as anti-liver/kidney microsome type 1 (LKM1) and/or anti-human formiminotransferase cyclodeaminase, formally known as anti-liver cytosol type 1 (LC1) define type 2 autoimmune hepatitis (AIH). The aims of this work are to develop a sensitive and specific test to detect anti-LKM1 and/or anti-LC1 autoantibodies and to establish the prevalence of anti-LC1. Sera from children with type 2 AIH (n=48) and those from a control group (n=100) were evaluated for anti-LKM1 and anti-LC1 by Enzyme-Linked Immunosorbent Assay (ELISA) and Western blotting. Each serum sample was assayed for reactivity against formiminotransferase cyclodeaminase and CYP2D6 alone or as part of a recombinant chimera protein. By ELISA with recombinant chimera protein, 50 serum samples were positive, 48 from patients with type 2 AIH and 2 from patients with chronic hepatitis C. Twenty-five of 48 (52%) patients studied were positive for both CYP2D6 and LC1 autoantibodies. Anti-LC1, either as the only marker or associated with anti-LKM1, was positive in 34/48 (71%). By Western blotting, anti-LC1 was found in 27/48 (56%) patients. This ELISA technique has proven to be antigen-specific and more sensitive than Western blot for the detection of anti-LC1 and anti-LKM1 autoantibodies. The prevalence of anti-LC1 (71%) confirms it as an important immunomarker in type 2 AIH.

  12. Studies on the distribution of hematopoietic bone marrow by bone marrow scintigraphy, 2

    International Nuclear Information System (INIS)

    Fujimori, Katsuhiko

    1976-01-01

    Distribution of the leukemic marrow was investigated in 42 cases by bone marrow scintigraphy using sup(99m)Tc sulfur colloid in association with clinical findings and ferrokinetics studies in order to clarify hematopoietic function in leukemia. 17 of chronic myelogenous leukemia, 3 of lymphatic leukemia, 2 of monocytic leukemia, 7 of atypical leukemia and one of erythroleukemia. 12 acute myelogenous leukemia were classified into 3 types A, B and C. Type A showed the distribution similar to those obtained with normal controls. Ferrokinetics studies, however, indicated complete absence of erythropoiesis. Type B showed complete lack of sup(99m)Tc activity in usual marrow sites, although ferrokinetics data showed normal erythropoeitic function. Type C showed abnormal concentration of sup(99m)Tc sulfur colloid in the tibiae. 17 chronic myelogenous leukemia showed reduced sup(99m)Tc activity in usual marrow sites and remarkable expanded marrow extending into distal femurs, proximal and distal tibiae and bones of feet. 2 acute lymphotic leukemia patients showed complete absence of sup(99m)Tc activity. The one chronic type showed almost normal distribution. Monocytic leukemia showed decreased marrow distribution in the sternum and vertebrae. Of 6 atypical leukemias one showed almost normal distribution. The others, including a case with hypoplastic luekemia, demonstrated marrow extension similar to that observed in chronic myelogenous leukemia or monocytic leukemia. Erythroleukemia showed increased concentrations of sup(99m)Tc activity in the usual marrow sites and marked marrow expansion throughout all long bones. These results suggest that there is a discrepancy between bone marrow distribution and hematopoietic function in the cases of acute myelogenous leukemia. (J.P.N.)

  13. Vascular homeostasis regulators, Edn1 and Agpt2, are upregulated as a protective effect of heat-treated zinc yeast in irradiated murine bone marrow

    International Nuclear Information System (INIS)

    Ueno, Megumi; Imadome, Kaori; Iwakawa, Mayumi; Anzai, Kazunori; Ikota, Nobuo; Imai, Takashi

    2010-01-01

    The purpose of this study was to elucidate the mechanism underlying the in vivo radioprotection activity by Zn-containing, heat-treated Saccharomyces cerevisiae yeast (Zn-yeast). Zn-yeast suspension was administered into C3H/He mice immediately after whole body irradiation (WBI) at 7.5 Gy. Bone marrow was extracted from the mice 6 hours after irradiation and analyzed on a microarray. Expression changes in the candidate responsive genes differentially expressed in treated mice were re-examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The bone marrow was also examined pathologically at 6 h, 3, 7, and 14 days postirradiation. Thirty-six genes, including Edn1 and Agpt2, were identified as candidate responsive genes in irradiated mouse bone marrow treated with Zn-yeast by showing a greater than three-fold change compared with control (no irradiation and no Zn-yeast) mice. The expressions of Cdkn1a, Bax, and Ccng, which are well known as radioresponsive genes, were upregulated in WBI mice and Zn-yeast treated WBI mice. Pathological examination showed the newly formed microvessels lined with endothelial cells, and small round hematopoietic cells around vessels in bone marrow matrix of mice administered with Zn-yeast after WBI, while whole-body irradiated mice developed fatty bone marrow within 2 weeks after irradiation. This study identified a possible mechanism for the postirradiation protection conferred by Zn-yeast. The protective effect of Zn-yeast against WBI is related to maintaining the bone marrow microenvironment, including targeting endothelial cells and cytokine release. (author)

  14. Toll-Like Receptor 4 in Bone Marrow-Derived Cells Contributes to the Progression of Diabetic Retinopathy

    Directory of Open Access Journals (Sweden)

    Hui Wang

    2014-01-01

    Full Text Available Diabetic retinopathy (DR is a major microvascular complication in diabetics, and its mechanism is not fully understood. Toll-like receptor 4 (TLR4 plays a pivotal role in the maintenance of the inflammatory state during DR, and the deletion of TLR4 eventually alleviates the diabetic inflammatory state. To further elucidate the mechanism of DR, we used bone marrow transplantation to establish reciprocal chimeric animals of TLR4 mutant mice and TLR4 WT mice combined with diabetes mellitus (DM induction by streptozotocin (STZ treatment to identify the role of TLR4 in different cell types in the development of the proinflammatory state during DR. TLR4 mutation did not block the occurrence of high blood glucose after STZ injection compared with WT mice but did alleviate the progression of DR and alter the expression of the small vessel proliferation-related genes, vascular endothelial growth factor (VEGF, and hypoxia inducible factor-1α (HIF-1α. Grafting bone marrow-derived cells from TLR4 WT mice into TLR4 mutant mice increased the levels of TNF-α, IL-1β, and MIP-2 and increased the damage to the retina. Similarly, VEGF and HIF-1α expression were restored by the bone marrow transplantation. These findings identify an essential role for TLR4 in bone marrow-derived cells contributing to the progression of DR.

  15. Bone marrow scintigraphy in hemopoietic depletion states

    International Nuclear Information System (INIS)

    Fortynova, J.; Bakos, K.; Pradacova, J.

    1981-01-01

    Bone marrow scintigraphy was performed in 29 patients with hemopoietic depletion states of various etiology. Two tracers were used for visualization, viz., sup(99m)Tc-sulfur-colloid and 111 InCl 3 ;some patients were examined using both indicators. 111 InCl 3 is bound to transferrin and is adsorbed on the surface of reticulocytes and erythroblasts. A scintillation camera PHO GAMMA SEARLE IV fitted with a moving table and computer CLINCOM were used to obtain whole-body images. The comparison of all scans and marrow puncture smears was done. In patients with aplastic anemia with both hyperplastic or hypoplastic marrow good correlation of bone marrow scans and sternal puncture smears was found. In several cases the scintigraphic examination helped to establish the diagnosis of marrow depletion. A peculiar disadvantage of the imaging method with either sup(99m)Tc-sulfur-colloid or 111 InCl 3 is that it shows the disorders in erythropoietic and reticuloendothelial cells whereas the defects in myelopoietic cell series and platelet precursors are not provable. According to literature data, great attention is paid to the prognostic value of scintigraphic examination in aplastic anemia. (author)

  16. Bone marrow scintigraphy in hemopoietic depletion states

    Energy Technology Data Exchange (ETDEWEB)

    Fortynova, J. (Ustav Hematologie a Krevni Transfuze, Prague (Czechoslovakia)); Bakos, K.; Pradacova, J. (Karlova Univ., Prague (Czechoslovakia). Biofyzikalni Ustav)

    1981-01-01

    Bone marrow scintigraphy was performed in 29 patients with hemopoietic depletion states of various etiology. Two tracers were used for visualization, viz., sup(99m)Tc-sulfur-colloid and /sup 111/InCl/sub 3/; some patients were examined using both indicators. /sup 111/InCl/sub 3/ is bound to transferrin and is adsorbed on the surface of reticulocytes and erythroblasts. A scintillation camera PHO GAMMA SEARLE IV fitted with a moving table and computer CLINCOM were used to obtain whole-body images. The comparison of all scans and marrow puncture smears was done. In patients with aplastic anemia with both hyperplastic or hypoplastic marrow good correlation of bone marrow scans and sternal puncture smears was found. In several cases the scintigraphic examination helped to establish the diagnosis of marrow depletion. A peculiar disadvantage of the imaging method with either sup(99m)Tc-sulfur-colloid or /sup 111/InCl/sub 3/ is that it shows the disorders in erythropoietic and reticuloendothelial cells whereas the defects in myelopoietic cell series and platelet precursors are not provable. According to literature data, great attention is paid to the prognostic value of scintigraphic examination in aplastic anemia.

  17. Shifting bone marrow edema of the knee

    International Nuclear Information System (INIS)

    Moosikasuwan, Josh B.; Schultz, Elizabeth; Miller, Theodore T.; Math, Kevin

    2004-01-01

    The purpose of our study is to describe shifting bone marrow edema in the knee as the MR imaging feature of intra-articular regional migratory osteoporosis of the knee. Five men, aged 45-73 years, were referred by orthopedic surgeons for MR imaging evaluation of knee pain, which had been present for 2 weeks to 6 months. One patient had a prior history of blunt trauma. None had risk factors for osteonecrosis. Four patients had two MR examinations and the patient with prior blunt trauma had four. Plain radiographs were obtained in all patients. In all cases, a large area of marrow edema initially involved a femoral condyle, with migration of the bone marrow edema to the other femoral condyle, tibia, and/or patella occurring over a 2- to 4-month period. Adjacent soft tissue edema was present in all five patients, while none had a joint effusion. Radiographs of two patients showed generalized osteopenia. In the absence of acute trauma or clinical suspicion of infection, a large area of bone marrow edema without a zone of demarcation may represent intra-articular regional migratory osteoporosis. Demonstration of shifting bone marrow edema on follow-up examinations suggests this diagnosis. (orig.)

  18. Effects of radiations on bone marrow

    International Nuclear Information System (INIS)

    Tubiana, M.; Frindel, E.; Croizat, H.; Parmentier, C.

    1979-01-01

    After total body irradiation for kidney transplant, the initial decrease of circulating blood cells is more rapid, the nadir is reached sooner and the regeneration occurs earlier when the doses are higher than a few hundred rads. The LD 50 in man seems to be higher than 450 rads. The in vivo and in vitro assays of hemopoietic stem cells have greatly increasedd the understanding of acute and late effects. Multipotential stem cells are very radiosensitive, furthermore the differentiation of the surviving stem cells is accelerated after irradiation. This results in a severe depletion of the stem cell compartment. When this stem cell number falls below a critical value, the stem cell no longer differentiates till the completion of the regeneration of the stem cell compartment. Stem cell proliferation is regulated by inhibitors and stimulators. Release of stimulators by irradiated bone marrow has been demonstrated. Severe sequellae are observed after irradiation of animal and human bone marrow. They seem to be due either to the damage of the stromal cell or to the stem cell population. In patients, four compensating mechanisms are observed after a regional bone marrow irradiation: stimulation of non irradiated bone marrow, extension of hemopoietic areas, regeneration of irradiated bone marrow when the irradiated volume is large and increase in the amplification factor resulting in an increase in the output of mature cells for one stem cell input. Assay of progenitor cells provides useful information and a reduction in their number is still observed many years after a large regional irradiation

  19. Abscopal suppression of bone marrow erythropoiesis

    International Nuclear Information System (INIS)

    Werts, E.D.; Johnson, M.J.; DeGowin, R.L.

    1978-01-01

    Abscopal responses of hemopoietic tissue, which we noted in preliminary studies of mice receiving partial-body irradiation, led us to clarify these effects. In studies reported here, one hind leg of CF-1 female mice received 1000, 5000, or 10,000 rad of x radiation. We found a persistent shift from medullary to splenic erythropoiesis preventing anemia in mice receiving 5000 or 10,000 rad. Splenectomy prior to 5000-rad irradiation resulted in anemia, which was not ameliorated by exposure to intermittent hypoxia. Despite evidence for increased levels of erythropoietin in the animals, namely, a reticulocytosis and increased erythrocyte radioiron incorporation, both 59 Fe uptake and erythroblast counts in shielded marrow remained below normal. We found 50 to 90% suppression of the growth of marrow stromal colonies (MSC) from bone marrow aspirates of the shielded and irradiated femoral marrow at 1 month and at least 20% depression of MSC at 1 year, with each dose. We conclude that: (i) high doses of x radiation to one leg of mice caused prolonged suppression of medullary erythropoiesis with splenic compensation to prevent anemia; (ii) splenectomy, anemia, and hypoxia prevented the severe abscopal depression of medullary erythropoiesis; and (iii) suppressed medullary erythropoiesis with decreased growth of MSC suggested a change in the hemopoietic microenvironment of the bone marrow

  20. Marrow donor registry and cord blood bank in Taiwan.

    Science.gov (United States)

    Lee, Tsung Dao

    2002-08-01

    Unrelated Bone marrow transplant was initiated thirty years ago. Though there are over millions of donors registered with the bone marrow registries worldwide, Asian patients rarely find a match with all these donors. Tzu Chi Marrow Donor Registry was established to meet this need. It has become the largest Asian marrow donor registry in the world. With the introduction of high technology to test the HLA of the donors and recipients, the success rate of bone marrow transplant is greatly improved among Asian countries. 50% of blood disease Asian patients who cannot find a bone marrow matched donor will be complemented by the establishment of cord blood banks in Taiwan.