WorldWideScience

Sample records for allogeneic radiation chimeras

  1. 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.)

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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.)

  9. 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

  10. 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.)

  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. 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

  13. 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

  14. 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)

  15. 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

  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. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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.

  3. 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

  4. 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)

  5. 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

  6. 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.)

  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. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  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. 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

  18. 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

  19. 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

  20. 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

  1. 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.

  2. 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

  3. 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.)

  4. 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

  5. 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

  6. Cytogenetic studies in dogs after total body irradiation and allogeneic transfusion with cryopreserved blood mononuclear cells: observations in long-term chimeras

    International Nuclear Information System (INIS)

    Carbonell, F.; Calvo, W.; Fliedner, T.M.; Kratt, E.; Gerhartz, H.; Koerbling, M.; Nothdurft, W.; Ross, W.M.

    1984-01-01

    Cytogenetic studies were performed on two dog groups after total body irradiation and allogeneic transfusion with cryopreserved blood mononuclear cells. The first group of dogs was transfused with unseparated leukocytes and suffered from graft-versus-host disease (GvHD). Cytogenetic studies demonstrated only cells of donor origin in all dogs of this group. The second group of animals was transfused with fraction 2 of a discontinuous albumin gradient. The dogs of this group did not develop GvHD, and the cytogenetic studies showed the presence of a mosaic of cells from donor and recipient origin in all of them. These results suggest that the GvHD may suppress autochthonous regeneration

  7. The fate of allogenic radiation sterilized bone grafts controlled by the electron spin resonance spectrometry

    International Nuclear Information System (INIS)

    Ostrowski, K.; Dziedzic-Goclawska, A.

    1981-01-01

    The normal fate of bone grafts is their resorption and substitution by the own host's bone tissue. This phenomenon described as creeping substitution process was controlled using biopsies from the grafted region in allogenic experimental system. Electron spin resonance (ESR) spectrometry was used for independent evaluation of resorption and substitution processes. The measurements were based on the process of induction in the hydroxyapatite (HA) crystals of bone mineral of stable paramagnetic centers which can be detected by ESR spectrometry. The loss of total amount of spins connected with the paramagnetic centers expressed in percent describes the kinetics of resorption. The changes in the concentration of spins due to the ''dilution'' of spins implanted with the graft by the nonirradiated ingrowing host's own bone describe the kinetics of the substitution process. Allogenic bone of calvaria was grafted orthotopically into rabbits after lyophilization and radiation sterilization with a dose of 3.5 Mrads. The process of graft's rebuilding was evaluated using the described ESR method. The application of the described technique in the human clinic is possible. (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. 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

  10. 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

  11. 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

  12. Effects of combined radiation-burn injury on survival rate of allogeneic skin grafts and immune reaction in rats

    International Nuclear Information System (INIS)

    Ran Xinze; Yan Yongtang; Cheng Tianmin; Li Yuan; Wei Shuqing

    1996-01-01

    The effects of combined radiation-burn injury on survival rate of allogeneic skin grafts and immune reaction were studied in rats with combined injury of 3-8 Gy 60 Co γ-ray irradiation plus 15% total body surface area full thickness burn induced by exposure to a 5 kw bromotungsten lamp. The allogeneic skin was transplanted 24 hours after injury. It was found that all the skin grafts failed to survive in 10 days and the immune reaction significantly increased in the early stage of burn injury. But the immune reaction was obviously suppressed by the combined radiation-burn injury. The survival rates of skin grafts were 20% and 30% in the combined injury of burn plus 3 and 4 Gy irradiation respectively. When the radiation doses increased to 5,6 and 8 Gy, the survival rates elevated to 69%, 88% and 100% respectively (in the group of 8 Gy, bone marrow transplantation was conducted before receiving skin graft). At day 30 post-transplantation the survival rates were still 36%, 42% and 100% respectively. Compared with burn group, there was a significant difference in survival rate when the radiation doses were higher than 5 Gy. These results indicate that the survival rate of the allogeneic skin graft increases concurrently with the increase in radiation dose and decreases with the elapse of the post-transplantation time

  13. 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.)

  14. 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

  15. The use of the mouse chimera assay to detect early embryonic damage from male mice exposed to low-dose radiation

    International Nuclear Information System (INIS)

    Oudiz, D.; Warner, P.; Walsh, K.J.; Wiley, L.

    1990-01-01

    Mouse chimeras are in vitro aggregations of two 4-cell embryos and are used to detect subtle, nonlethal changes, which are expressed as a proliferative disadvantage in exposed embryos. One of the embryos is labeled with a viable dye (FITC) in order to determine the relative cellular contribution of each embryo when the chimera is dissociated 40 hours later. This proliferative disadvantage has been seen at doses which do not produce an effect on cell number when the embryos are cultured singly. Previously, the assay has detected a decrease in cellular proliferation in embryos from male mice exposed to a single dose of x-radiation as low as 0.05 Gy. In the current study, male mice were irradiated with a single dose of 0, 0.001, 0.01, or 0.05 Gy, and then serially mated for the next 8 weeks to unexposed females. Chimeras were constructed from control and treated embryos. Embryos from males treated with 0.05 Gy exhibited a significant decrease in cellular proliferation during weeks 6 and 7 post-irradiation. A similar decrease was seen in the males treated with 0.01 Gy. No reductions were observed from embryos cultured singly in any of the treatment groups

  16. 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.

  17. 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

  18. Allogeneic tumor cell vaccines

    Science.gov (United States)

    Srivatsan, Sanjay; Patel, Jaina M; Bozeman, Erica N; Imasuen, Imade E; He, Sara; Daniels, Danielle; Selvaraj, Periasamy

    2014-01-01

    The high mortality rate associated with cancer and its resistance to conventional treatments such as radiation and chemotherapy has led to the investigation of a variety of anti-cancer immunotherapies. The development of novel immunotherapies has been bolstered by the discovery of tumor-associated antigens (TAAs), through gene sequencing and proteomics. One such immunotherapy employs established allogeneic human cancer cell lines to induce antitumor immunity in patients through TAA presentation. Allogeneic cancer immunotherapies are desirable in a clinical setting due to their ease of production and availability. This review aims to summarize clinical trials of allogeneic tumor immunotherapies in various cancer types. To date, clinical trials have shown limited success due potentially to extensive degrees of inter- and intra-tumoral heterogeneity found among cancer patients. However, these clinical results provide guidance for the rational design and creation of more effective allogeneic tumor immunotherapies for use as monotherapies or in combination with other therapies. PMID:24064957

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.)

  4. 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-

  5. 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

  6. 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...

  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. 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. 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

  11. 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.

  12. 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)

  13. 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.

  14. Experimental study on therapy of acute radiation sickness with transplantation of allogeneic peripheral blood hemopoietic stem cells

    International Nuclear Information System (INIS)

    Ma Enpu; Bi Jianjin; Zhan Aiqin

    1995-01-01

    In the study, 10 beagles were used. All the dogs were irradiated with 6.5 Gy of γ-rays from a 60 Co source (dose rate, 95.6-107.9 R/min) and divided into three groups. All the three dogs in the control group died, having survived 7.5 days on the average after irradiation. In the second group, four dogs were transplanted with allogeneic peripheral blood hemopoietic stem cells (PBHSC) without removing T lymphocytes. The results of sex chromosome tests after irradiation and transplantation showed that the cells were of donor type. All the four dogs died of severe graft versus-host disease (GVHD) and survived 41.6 days on the average after irradiation. In the third group, three dogs received transplantation of allogeneic PBHSC without T lymphocytes. Two of them died, and the third developed mild GVHD and survived over 4 years

  15. 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

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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)

  4. 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

  5. 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

  6. 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.

  7. 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.

  8. Kosten van allogene stamceltransplantaties

    NARCIS (Netherlands)

    M. van Agthoven (Michel); M.T. Groot (Martijn); C.A. Uyl-de Groot (Carin)

    2001-01-01

    textabstractAllogene stamceltransplantatie is een topspecialistische procedure die met succes kan worden ingezet in de behandeling van (hematologische) maligniteiten, met name bij leukemie. Van oudsher worden transplantaten van verwante donoren gebruikt, maar met de mogelijkheden om transplantaten

  9. 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)

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. Split tolerance in nude mice transplanted with 2'-deoxyguanosine-treated allogeneic thymus lobes

    International Nuclear Information System (INIS)

    Suzuki, G.; Moriyama, T.; Takeuchi, Y.; Kawase, Y.; Habu, S.

    1989-01-01

    To elucidate the acquisition of self tolerance in the thymus, full-allogeneic thymic chimeras were constructed. Athymic C3H and BALB/c nude mice were reconstituted with the thymic lobes of BALB/c and B10.BR fetuses, respectively, that were organ cultured for 5 days in the presence of 2'-deoxyguanosine. T cells in these chimeras were tolerized to the host MHC in both MLR and CTL assays. In contrast, T cells in the chimeras exhibited split tolerance for the thymic MHC haplotype. CTL specific for class I MHC of the thymic haplotype were generated not only from the peripheral T cells of the chimeras but also from thymocytes re-populated in the engrafted thymic lobes. However, T cells in these chimeras responded poorly to the class II MHC of the thymic haplotype in a standard MLR assay. In a syngeneic MLR culture upon stimulation with enriched APC of the thymic haplotype, only 22 to 48% of the responses were mediated by CD4+ cells, and proliferations of CD4- cells were prominent. There were no haplotype-specific suppressor cells detected which would cause the unresponsiveness to the thymic class II MHC. These results indicated that the thymic lobes treated with 2'-deoxyguanosine were defective in the ability to induce the transplantation tolerance for the class I MHC expressed on the thymus, although the same thymic lobes were able to induce the transplantation tolerance for the thymic class II MHC

  15. 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...

  16. 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.

  17. 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.

  18. 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)

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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...

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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...

  11. 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...

  12. 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.)

  13. 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.

  14. 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...

  15. 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.

  16. 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.

  17. 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.

  18. 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)

  19. Chimera of new nuclear materials

    International Nuclear Information System (INIS)

    Bush, S.H.

    1975-01-01

    The current and future needs in materials for light water reactors and liquid metal fast breeder reactors are reviewed. Information and discussions are included on boiling water reactors, pressurized water reactors, liquid metal fast breeder reactors, corrosion of piping systems and steam generators, ferritic steels, stainless steels, Inconel 600, pressure vessels, and radiation damage. (U.S.)

  20. 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...

  1. 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)

  2. 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.

  3. 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)

  4. 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...

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. Allogeneic tumor cell vaccines: the promise and limitations in clinical trials.

    Science.gov (United States)

    Srivatsan, Sanjay; Patel, Jaina M; Bozeman, Erica N; Imasuen, Imade E; He, Sara; Daniels, Danielle; Selvaraj, Periasamy

    2014-01-01

    The high mortality rate associated with cancer and its resistance to conventional treatments such as radiation and chemotherapy has led to the investigation of a variety of anti-cancer immunotherapies. The development of novel immunotherapies has been bolstered by the discovery of tumor-associated antigens (TAAs), through gene sequencing and proteomics. One such immunotherapy employs established allogeneic human cancer cell lines to induce antitumor immunity in patients through TAA presentation. Allogeneic cancer immunotherapies are desirable in a clinical setting due to their ease of production and availability. This review aims to summarize clinical trials of allogeneic tumor immunotherapies in various cancer types. To date, clinical trials have shown limited success due potentially to extensive degrees of inter- and intra-tumoral heterogeneity found among cancer patients. However, these clinical results provide guidance for the rational design and creation of more effective allogeneic tumor immunotherapies for use as monotherapies or in combination with other therapies.

  12. 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)

  13. 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.

  14. 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.

  15. 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.

  16. Utility of the inspiratory phase in high-resolution computed tomography evaluations of pediatric patients with bronchiolitis obliterans after allogeneic bone marrow transplant: reducing patient radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Togni Filho, Paulo Henrique; Casagrande, Joao Luiz Marin; Lederman, Henrique Manoel, E-mail: paulotognifilho@gmail.com [Universidade Federal de Sao Paulo (EPM/UNIFESP), Sao Paulo, SP (Brazil). Escola Paulista de Medicina. Dept. of Diagnostico por Imagem; Universidade de Sao Paulo (InRad/HC/FMUSP), Sao Paulo, SP (Brazil). Hospital das Clinicas. Instituto de Radiologia

    2017-03-15

    Objective: To evaluate the utility of the inspiratory phase in high-resolution computed tomography (HRCT) of the chest for the diagnosis of post-bone marrow transplantation bronchiolitis obliterans. Materials and Methods: This was a retrospective, observational, cross-sectional study. We selected patients of either gender who underwent bone marrow transplantation and chest HRCT between March 1, 2002 and December 12, 2014. Ages ranged from 3 months to 20.7 years. We included all examinations in which the HRCT was performed appropriately. The examinations were read by two radiologists, one with extensive experience in pediatric radiology and another in the third year of residency, who determined the presence or absence of the following imaging features: air trapping, bronchiectasis, alveolar opacities, nodules, and atelectasis. Results: A total of 222 examinations were evaluated (mean, 5.4 ± 4.5 examinations per patient). The expiratory phase findings were comparable to those obtained in the inspiratory phase, except in one patient, in whom a small uncharacteristic nodule was identified only in the inspiratory phase. Air trapping was identified in a larger number of scans in the expiratory phase than in the inspiratory phase, as was atelectasis, although the difference was statistically significant only for air trapping. Conclusion: In children being evaluated for post-bone marrow transplantation bronchiolitis obliterans, the inspiratory phase can be excluded from the chest HRCT protocol, thus reducing by half the radiation exposure in this population. (author)

  17. Utility of the inspiratory phase in high-resolution computed tomography evaluations of pediatric patients with bronchiolitis obliterans after allogeneic bone marrow transplant: reducing patient radiation exposure

    International Nuclear Information System (INIS)

    Togni Filho, Paulo Henrique; Casagrande, Joao Luiz Marin; Lederman, Henrique Manoel; Universidade de Sao Paulo

    2017-01-01

    Objective: To evaluate the utility of the inspiratory phase in high-resolution computed tomography (HRCT) of the chest for the diagnosis of post-bone marrow transplantation bronchiolitis obliterans. Materials and Methods: This was a retrospective, observational, cross-sectional study. We selected patients of either gender who underwent bone marrow transplantation and chest HRCT between March 1, 2002 and December 12, 2014. Ages ranged from 3 months to 20.7 years. We included all examinations in which the HRCT was performed appropriately. The examinations were read by two radiologists, one with extensive experience in pediatric radiology and another in the third year of residency, who determined the presence or absence of the following imaging features: air trapping, bronchiectasis, alveolar opacities, nodules, and atelectasis. Results: A total of 222 examinations were evaluated (mean, 5.4 ± 4.5 examinations per patient). The expiratory phase findings were comparable to those obtained in the inspiratory phase, except in one patient, in whom a small uncharacteristic nodule was identified only in the inspiratory phase. Air trapping was identified in a larger number of scans in the expiratory phase than in the inspiratory phase, as was atelectasis, although the difference was statistically significant only for air trapping. Conclusion: In children being evaluated for post-bone marrow transplantation bronchiolitis obliterans, the inspiratory phase can be excluded from the chest HRCT protocol, thus reducing by half the radiation exposure in this population. (author)

  18. 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.

  19. 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.

  20. 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....

  1. [Alternatives to allogenous blood transfusion].

    Science.gov (United States)

    Cernea, Daniela; Vlădoianu, Alice; Stoica, Maria; Novac, M; Berteanu, Cristina

    2009-01-01

    Blood transfusion is usually meant to lower morbidity and mortality rates. Allogenous blood transfusion implies certain risks that can be avoided by autologous blood transfusions techniques including: preoperatory autologous blood donation, acute normovolemic hemodilution, intraoperatory and postoperatory blood salvage. Preoperatory blood donation and acute normovolemic hemodilution are used for planned interventions with an estimated blood loss higher than 20% of blood volume. These methods imply Erythropoietin and iron treatment. Intraoperatory and postoperatory blood salvage is performed by personnel trained in blood donation, handling and storage. Autologous blood transfusions are used for certain surgical procedures that commonly require transfusions: orthopedic surgery, radical prostatectomy, cardiovascular surgery, organ transplantation. An alternative to allogenous blood transfusion is the use of artificial oxygen transporters: human or animal hemoglobin solutions or pefluorocarbonate solutions. These solutions do not require cross reactions, do not carry diseases and are generally well tolerated and easily stored in the operating room, ambulance and other transport means. They have however a slight degree of toxicity.

  2. Allogenic bone grafts in post-traumatic juxta-articular defects: Need for allogenic bone banking.

    Science.gov (United States)

    Mishra, Anil Kumar; Vikas, Rohit; Agrawal, H S

    2017-07-01

    Allogenic bone banking provide both structural and granular bone grafts for various orthopaedic, spinal, oncological and dental surgeries. However allogenic bones, presently, are not readily available. This article discusses the clinical applications of the allogenic grafts, the screening criteria and procedure for maintenance of such a bone banking facility. This article demonstrates the effective role of allogenic bone in a case of post-traumatic bone loss situation and discusses the growing need and present situation of bone banking in our country.

  3. 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...

  4. 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.

  5. 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)

  6. Kidney dysfunction after allogeneic stem cell transplantation

    NARCIS (Netherlands)

    Kersting, S.

    2008-01-01

    Allogeneic stem cell transplantation (SCT) is a widely accepted approach for malignant and nonmalignant hematopoietic diseases. Unfortunately complications can occur because of the treatment, leading to treatment-related mortality. We studied kidney dysfunction after allogeneic SCT in 2 cohorts of

  7. Tetanus after allogeneic bone-marrow transplantation

    International Nuclear Information System (INIS)

    Kendra, J.R.; Halil, O.; Barrett, A.J.; Selwyn, S.

    1982-01-01

    A brief report is presented of a case of tetanus after allogeneic bone-marrow transplantation complicated by radiation-induced pneumonitis. A 30-year-old army sergeant received a bone-marrow transplant from his brother for the treatment of a granulocytic sarcoma after local radiotherapy to the tumour. Six years earlier he had sustained an open, compound fracture of the left tibia and fibula while on army exercise. At the time a pin and plate had been inserted and booster anti-tetanus administered. Bone-marrow transplantation was performed after total body irradiation. Cyclosporin A was given against graft-versus-host disease. Fifty four days after transplantation tetanus was diagnosed and death followed 14 days later. Necropsy disclosed radiation-induced pneumonitis, but no organisms were cultured from the lungs or the old fracture site. It is suggested that spores were incorporated into the wound site before surgery and that oxygenation around the plate became compromised after transplantation, permitting germination of dormant spores, immunosuppression allowing development of the disease. (U.K.)

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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...

  14. 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.

  15. 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...

  16. 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...

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. 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

  3. 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

  4. Allogeneic Peripheral Blood Stem Cell Harvest

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Allogeneic Peripheral Blood Stem Cell Harvest. Mobilization protocol. G-CSF 10 mcg/Kg / day for 5 days. Pheresis. Cobe Spectra; Haemonetics mcs+. Enumeration. CD34 counts; Cfu-GM assays.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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)

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. Alternatives to allogeneic platelet transfusion.

    Science.gov (United States)

    Desborough, Michael J R; Smethurst, Peter A; Estcourt, Lise J; Stanworth, Simon J

    2016-11-01

    Allogeneic platelet transfusions are widely used for the prevention and treatment of bleeding in thrombocytopenia. Recent evidence suggests platelet transfusions have limited efficacy and are associated with uncertain immunomodulatory risks and concerns about viral or bacterial transmission. Alternatives to transfusion are a well-recognised tenet of Patient Blood Management, but there has been less focus on different strategies to reduce bleeding risk by comparison to platelet transfusion. Direct alternatives to platelet transfusion include agents to stimulate endogenous platelet production (thrombopoietin mimetics), optimising platelet adhesion to endothelium by treating anaemia or increasing von Willebrand factor levels (desmopressin), increasing formation of cross-linked fibrinogen (activated recombinant factor VII, fibrinogen concentrate or recombinant factor XIII), decreasing fibrinolysis (tranexamic acid or epsilon aminocaproic acid) or using artificial or modified platelets (cryopreserved platelets, lyophilised platelets, haemostatic particles, liposomes, engineered nanoparticles or infusible platelet membranes). The evidence base to support the use of these alternatives is variable, but an area of active research. Much of the current randomised controlled trial focus is on evaluation of the use of thrombopoietin mimetics and anti-fibrinolytics. It is also recognised that one alternative strategy to platelet transfusion is choosing not to transfuse at all. © 2016 John Wiley & Sons Ltd.

  16. Allogenic lyophilized cartilage grafts for craniomaxillofacial reconstruction

    International Nuclear Information System (INIS)

    Pill Hoon Choung

    1999-01-01

    Allogenic lyophilized cartilages were made in our clinic after Sailer methods and some modification. In our clinic, we have used allogenic cartilage grafts on 102 defects of craniomaxillofacial area; 1) for defects from cyst or ameloblastoma, 2) for lack of continuity of the mandible, 3) for rhinoplasty, 4) for paranasal augmentation, 5) for augmentation genioplasty, 6) for reconstruction of orbital floor, 7) for oroantral fistula, 8) for temporal augmentation, 9) for TMJ surgery 10) for condyle defect as a costochondral graft, 11) for filling of tooth socket and alveolus augmentation,12) for correction or orbital height and 13) for guided bone regeneration in peripheral implant. The types of lyophilized cartilage used were chip, sheet and block types developed by freeze-dried methods. Some grafts showed change of ossification, in which case we could perform implant on it. We have good results on reconstruction of craniomaxillofacial defects. Allogenic cartilage have advantages such as 1) it has no immune reaction clinically, 2) it is more tolerable to infection than that of autogenous cartilage, 3) it has character of less resorption which require no over correction, 4) it is easy to manipulate contouring, and 5) it has possibility of undergoing ossification. Allogenic cartilage has been considered as good substitutes for bone. The author would like to report the results on 102 allogenic cartilage have

  17. 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.

  18. 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

  19. 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

  20. 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

  1. 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 ...

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. ALLOGENEIC TRANSPLANTATION FOR CHRONIC LYMPHOCYTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Luca Laurenti

    2010-08-01

    Full Text Available Even if Chronic lymphocytic leukemia (CLL often has an indolent behavior with good responsiveness to cytoreductive treatment, about 20% of the patients, so called "poor-risk" patients, show an aggressive course and die within a few years despite early intensive therapies. Criteria for poor-risk disease according to the European Bone Marrow Transplantation (EBMT CLL Transplant Consensus are: purine analogue refractoriness, early relapse after purine analogue combination therapy, CLL with p53 lesion requiring treatment. Allogeneic transplant has potential curative role in CLL, however burden with very  high transplant related mortality (TRM rates of 38-50%: A major advance in reducing the short-term morbidity and mortality of allogeneic stem cell transplantation (SCT has been the introduction of non-myeloablative or reduced intensity conditioning (RIC regimens to allow engraftment of allogeneic stem cells. There is no doubt that the crucial therapeutic principle of allo-SCT in CLL is graft versus leukemia (GVL activity. The major complications of allogeneic SCT in CLL are: chronic graft-versus-host-disease (GVHD affecting quality of life, high graft rejection and infection rates rates correlated with preexisting immunosuppression. Disease relapse remains the major cause of failure after RIC allo-HCT in CLL patients. Sensitive minimal residual disease (MRD quantification has strong prognostic impact after transplant.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. Effect of allogenic thymic cells on radioleukaemogenesis in AKR-T1ALD mice

    International Nuclear Information System (INIS)

    Legrand, E.; Sankar-Mistry, P.; Kressmann, M.C.

    1975-01-01

    When AKR mice are irradiated with a sub-lethal dose (4 times 175 R), thymic lymphosarcomas (L.S.) occur earlier than in controls. This accelerated leukaemogenesis is not inhibited by syngenic restoration with bone marrows cells (BM). Using the AKR/T1ALD substrain which bears 38 chromosomes with 1 metacentric markers, it has been shown that AKR radio-chimaeras restored by T1ALD BM developed two kinds of L.S.: early (radiation-induced) L.S. originating mainly from host cells surviving irradiation and late L.S. from donor cells. The experiments were to investigate the potential influence of normal allogenic thymic cells, with or without syngenic B.M., on the incidence, latency and origin of LS appearing in irradiated AKR recipients. Adding C3H allogenic thymic cells to syngenic B.M. increases the percentage of early L.S. whose latencies are unchanged. Besides, when C3H thymic cells are injected to irradiated controls without syngenic B.M. cells, L.S. are seen to occur significantly earlier than in just the irradiated animals alone. In radio-chimaeras restored by allogenic thymic cells and syngenic B.M., except in one case, all the L.S. were seen to originate from B.M. cells. The interpretation of these results depends on the possible role of allogenic thymic cells on host cells surviving the irradiation, or the exogeneous B.M. In the first case, allogenic thymocytes could induce a graft versus host reaction increasing the post-irradiation depletion of lymphoid system and hastening thymic endoregeneration which is supposed to be the first step towards leukaemogenesis. The second hypothesis, which seems the most likely, would be that C1H thymic cells could selectively act on host cells surviving irradiation and enhance the differenciation of haemopoietic precursors at the expense of the lymphoid cells [fr

  20. 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

  1. ALLOGENEIC TRANSPLANTATION FOR CHRONIC LYMPHOCYTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Patrizia Chiusolo

    2010-05-01

    Full Text Available

    Even if Chronic lymphocytic leukemia (CLL often has an indolent behavior with good responsiveness to cytoreductive treatment, about 20% of the patients, so called "poor-risk" patients, show an aggressive course and die within a few years despite early intensive therapies. Criteria for poor-risk disease according to the European Bone Marrow Transplantation (EBMT CLL Transplant Consensus are: purine analogue refractoriness, early relapse after purine analogue combination therapy, CLL with p53 lesion requiring treatment.

    Allogeneic transplant has potential curative role in CLL, however burden with very  high transplant related mortality (TRM rates of 38-50%:

    A major advance in reducing the short-term morbidity and mortality of allogeneic stem cell transplantation (SCT has been the introduction of non-myeloablative or reduced intensity conditioning (RIC regimens to allow engraftment of allogeneic stem cells. There is no doubt that the crucial therapeutic principle of allo-SCT in CLL is graft versus leukemia (GVL activity.

    The major complications of allogeneic SCT in CLL are: chronic graft-versus-host-disease (GVHD affecting quality of life, high graft rejection and infection rates rates correlated with preexisting immunosuppression. Disease relapse remains the major cause of failure after RIC allo-HCT in CLL patients.

    Sensitive minimal residual disease (MRD quantification has strong prognostic impact after transplant.

     

  2. 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.

  3. Frequent induction of chromosomal aberrations in in vivo skin fibroblasts after allogeneic stem cell transplantation: hints to chromosomal instability after irradiation

    International Nuclear Information System (INIS)

    Massenkeil, G.; Zschieschang, P.; Thiel, G.; Hemmati, P. G.; Budach, V.; Dörken, B.; Pross, J.; Arnold, R.

    2015-01-01

    Total body irradiation (TBI) has been part of standard conditioning regimens before allogeneic stem cell transplantation for many years. Its effect on normal tissue in these patients has not been studied extensively. We studied the in vivo cytogenetic effects of TBI and high-dose chemotherapy on skin fibroblasts from 35 allogeneic stem cell transplantation (SCT) patients. Biopsies were obtained prospectively (n = 18 patients) before, 3 and 12 months after allogeneic SCT and retrospectively (n = 17 patients) 23–65 months after SCT for G-banded chromosome analysis. Chromosomal aberrations were detected in 2/18 patients (11 %) before allogeneic SCT, in 12/13 patients (92 %) after 3 months, in all patients after 12 months and in all patients in the retrospective group after allogeneic SCT. The percentage of aberrant cells was significantly higher at all times after allogeneic SCT compared to baseline analysis. Reciprocal translocations were the most common aberrations, but all other types of stable, structural chromosomal aberrations were also observed. Clonal aberrations were observed, but only in three cases they were detected in independently cultured flasks. A tendency to non-random clustering throughout the genome was observed. The percentage of aberrant cells was not different between patients with and without secondary malignancies in this study group. High-dose chemotherapy and TBI leads to severe chromosomal damage in skin fibroblasts of patients after SCT. Our long-term data suggest that this damage increases with time, possibly due to in vivo radiation-induced chromosomal instability

  4. 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)

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. Complications of allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Arnaout, Karim; Patel, Nihar; Jain, Maneesh; El-Amm, Joelle; Amro, Farah; Tabbara, Imad A

    2014-08-01

    Infection, graft-versus-host disease (GVHD), and to a lesser extent sinusoidal obstructive syndrome (SOS) represent the major causes of morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (AHSCT). During the last decade, progress in prevention and treatment of these complications led to improvement in the outcome of these patients. Despite the fact that nonmyeloablative regimens have been increasingly used in elderly patients and in patients with co-morbidities, the nonrelapse related mortality remains a challenge and long-term follow-up is required. The objective of this manuscript is to provide an updated concise review of the complications of AHSCT and of the available treatment interventions.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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)

  16. Current issues in allogeneic islet transplantation.

    Science.gov (United States)

    Chang, Charles A; Lawrence, Michael C; Naziruddin, Bashoo

    2017-10-01

    Transplantation of allogenic pancreatic islets is a minimally invasive treatment option to control severe hypoglycemia and dependence on exogenous insulin among type 1 diabetes (T1D) patients. This overview summarizes the current issues and progress in islet transplantation outcomes and research. Several clinical trials from North America and other countries have documented the safety and efficacy of clinical islet transplantation for T1D patients with impaired hypoglycemia awareness. A recently completed phase 3 clinical trial allows centres in the United States to apply for a Food and Drug Administration Biologics License for the procedure. Introduction of anti-inflammatory drugs along with T-cell depleting induction therapy has significantly improved long-term function of transplanted islets. Research into islet biomarkers, immunosuppression, extrahepatic transplant sites and potential alternative beta cell sources is driving further progress. Allogeneic islet transplantation has vastly improved over the past two decades. Success in restoration of glycemic control and hypoglycemic awareness after islet transplantation has been further highlighted by clinical trials. However, lack of effective strategies to maintain long-term islet function and insufficient sources of donor tissue still impose limitations to the widespread use of islet transplantation. In the United States, wide adoption of this technology still awaits regulatory approval and, importantly, a financial mechanism to support the use of this technology.

  17. 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.

  18. 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....

  19. 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.

  20. 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.

  1. 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.

  2. Protection of lethally irradiated mice with allogeneic fetal liver cells: influence of irradiation dose on immunologic reconstitution

    International Nuclear Information System (INIS)

    Tulunay, O.; Good, R.A.; Yunis, E.J.

    1975-01-01

    After lethal irradiation long-lived, immunologically vigorous C3Hf mice were produced by treatment with syngeneic fetal liver cells or syngeneic newborn or adult spleen cells. Treatment of lethally irradiated mice with syngeneic or allogeneic newborn thymus cells or allogeneic newborn or adult spleen cells regularly led to fatal secondary disease or graft-versus-host reactions. Treatment of the lethally irradiated mice with fetal liver cells regularly yielded long-lived, immunologically vigorous chimeras. The introduction of the fetal liver cells into the irradiated mice appeared to be followed by development of immunological tolerance of the donor cells. The findings suggest that T-cells at an early stage of differentiation are more susceptible to tolerance induction than are T-lymphocytes at later stages of differentiation. These investigations turned up a perplexing paradox which suggests that high doses of irradiation may injure the thymic stroma, rendering it less capable of supporting certain T-cell populations in the peripheral lymphoid tissue. Alternatively, the higher and not the lower dose of irradiation may have eliminated a host cell not readily derived from fetal liver precursors which represents an important helper cell in certain cell-mediated immune functions, e.g., graft-versus-host reactions, but which is not important in others, e.g., allograft rejections. The higher dose of lethal irradiation did not permit development or maintenance of a population of spleen cells that could initiate graft-versus-host reactions but did permit the development of a population of donor cells capable of achieving vigorous allograft rejection

  3. 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.

  4. 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.

  5. 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.

  6. 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)

  7. 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.

  8. 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.

  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. Radiation

    International Nuclear Information System (INIS)

    2013-01-01

    The chapter one presents the composition of matter and atomic theory; matter structure; transitions; origin of radiation; radioactivity; nuclear radiation; interactions in decay processes; radiation produced by the interaction of radiation with matter

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. Allogeneic cellular immunotherapy for chronic B-cell leukemia

    NARCIS (Netherlands)

    Hoogendoorn, Mels

    2007-01-01

    Allogeneic stem cell transplantation (SCT) following reduced-intensity conditioning (RIC) as treatment modality has curative potential in patients suffering from chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL), illustrating susceptibility of these leukemic cells for the

  17. 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.

  18. 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.

  19. Present and future of allogeneic natural killer cell therapy

    Directory of Open Access Journals (Sweden)

    Okjae eLim

    2015-06-01

    Full Text Available Natural killer (NK cells are innate lymphocytes that are capable of eliminating tumor cells and are therefore used for cancer therapy. Although many early investigators used autologous NK cells, including lymphokine-activated killer cells, the clinical efficacies were not satisfactory. Meanwhile, human leukocyte antigen (HLA-haploidentical hematopoietic stem cell transplantation revealed the anti-tumor effect of allogeneic NK cells, and HLA-haploidentical, killer cell immunoglobulin-like receptor (KIR ligand-mismatched allogeneic NK cells are currently used for many protocols requiring NK cells. Moreover, allogeneic NK cells from non-HLA-related healthy donors have been recently used in cancer therapy. The use of allogeneic NK cells from non-HLA-related healthy donors allows the selection of donor NK cells with higher flexibility and to prepare expanded, cryopreserved NK cells for instant administration without delay for ex vivo expansion. In cancer therapy with allogeneic NK cells, optimal matching of donors and recipients is important to maximize the efficacy of the therapy. In this review, we summarize the present state of allogeneic NK cell therapy and its future directions.

  20. 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

  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. The effect of in vitro irradiation on the responses of human lymphocytes to PHA, PPD and allogeneic cells

    International Nuclear Information System (INIS)

    Herva, E.; Kiviniitty, K.; Oulu Univ.

    1975-01-01

    The effect of X-ray, cobalt and 45 MeV electron irradiation on the responses of lymphocytes to PHA, PPD and allogeneic cells was studied using a semimicro lymphocyte culture technique. The responses to PPD and allogeneic cells were found to be more sensitive to irradiation than the response to PHA, even when the time factor was taken into account, i.e. the effect of irradiation was measured on the same day irrespective the type os stimulation. At the doses used, 500, 3,000 and 6,000 rd, there was no difference between the effects of the three types of radiation used. The possible explanations for the findings are discussed. (orig.) [de

  4. Ocular findings after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Tabbara, Khalid F; Al-Ghamdi, Ahmad; Al-Mohareb, Fahad; Ayas, Mouhab; Chaudhri, Naeem; Al-Sharif, Fahad; Al-Zahrani, Hazzaa; Mohammed, Said Y; Nassar, Amr; Aljurf, Mahmoud

    2009-09-01

    To study the incidence, causes, and outcome of major ocular complications in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Retrospective, noncomparative, observational clinical study. The study included a total of 620 patients who underwent allogeneic HSCT in the period from 1997 to 2007 at King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. Allogeneic HSCT. Patients with ocular complications were referred to the ophthalmology division for complete ophthalmologic examination, including visual acuity, tonometry, Schirmer test, biomicroscopy, and dilated ophthalmoscopy. Laboratory investigations were performed whenever indicated. The incidence and causes of major ocular complications after allogeneic HSCT were determined. Visual acuity at 1 year after allogeneic HSCT was recorded. Major ocular complications occurred in 80 (13%) of 620 patients who underwent allogeneic HSCT. There were 36 male patients (45%) and 44 female patients (55%) with a mean age of 29 years and an age range of 9 to 65 years. Prophylaxis for graft-versus-host disease (GVHD) consisted of cyclosporine and methotrexate in 69 patients, and cyclosporine, methotrexate and corticosteroids, or mycophenolate mofetil in 11 patients. The most frequently encountered ocular complications were chronic GVHD, dry eye syndrome without GVHD, corneal ulcers, cataract, glaucoma, cytomegalovirus retinitis, fungal endophthalmitis, and acquisition of allergic conjunctivitis from atopic donors. There was no correlation between the pattern of ocular complications and the transplanted stem cell source. Best-corrected visual acuity (BCVA) at 1 year after transplantation was less than 20/200 in 13 patients (16%), less than 20/50 in 17 patients (21%), and better than 20/50 in 50 patients (63%). Ocular complications are common in patients undergoing allogeneic HSCT. Early recognition and prompt treatment are important. The author(s) have no proprietary or commercial

  5. 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.

  6. 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

  7. A standardized multidisciplinary approach reduces the use of allogeneic blood products in patients undergoing cardiac surgery

    NARCIS (Netherlands)

    van der Linden, P.; de Hert, S.; Daper, A.; Trenchant, A.; Jacobs, D.; de Boelpaepe, C.; Kimbimbi, P.; Defrance, P.; Simoens, G.

    2001-01-01

    PURPOSE: Individual and institutional practices remain an independent predictor factor for allogeneic blood transfusion. Application of a standardized multidisciplinary transfusion strategy should reduce the use of allogeneic blood transfusion in major surgical patients. METHODS: This prospective

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. Bacterial infections associated with allogenic bone transplantation

    Directory of Open Access Journals (Sweden)

    Stepanović Željko Lj.

    2015-01-01

    Full Text Available Background/Aim. Bone allografts are frequently used in orthopedic reconstructive procedures carrying a high risk for recipients. To assess the nature and frequency of allograft contamination and associated surgical infection the case records from our institutional bone bank were reviewed. Methods. We retrospectively analyzed the microbiology of discarded bone allografts and the surgical site of the recipients. A case series of patients who acquired surgical site infection after allogenic bone transplantation was presented. Swab culturing was conducted on 309 femoral heads from living donors who underwent partial and total hip arthroplasty between January 2007 and December 2013. To prevent potential bone allograft contamination we used saline solution of 2.0 mg/ml of amikacin during thawing. The overall infection rate was analyzed in 197 recipients. Results. Of the 309 donated femoral heads, 37 were discarded due to bacterial contamination, giving the overall contamination rate of 11.97%. The postoperative survey of 213 bone allotransplantations among 197 recipients showed the infection rate of 2.03%. The coagulase-negative Staphylococcus was the most commonly identified contaminant of bone allografts and recipient surgical sites. Conclusion. The allograft contamination rate and the infection rate among recipients in our institution are in accordance with the international standards. The coagulase-negative Staphylococcus was the most commonly identified contaminant of bone allografts and recipient surgical sites. There is no strong evidence that surgical site infections were associated with bone allograft utilization. We plan further improvements in allograft handling and decontamination with highly concentrated antibiotic solutions in order to reduce infection risk for recipients.

  14. 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.

  15. 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.

  16. 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.

  17. Ready-made allogeneic ABO-specific serum eye drops

    DEFF Research Database (Denmark)

    Harritshøj, Lene Holm; Nielsen, Connie; Ullum, Henrik

    2014-01-01

    serum treatment. CONCLUSION: Ready-made ABO-identical allogeneic serum eye drops were straightforwardly produced, quality-assured and registered as a safe standard blood product for the treatment of certain cases of severe dry eye disease. Therapeutic efficacy was comparable to previous reports......PURPOSE: To overcome problems and delays of the preparation of autologous serum eye drops, a production line of ABO-specific allogeneic serum eye drops from male blood donors was set up in a blood bank. Feasibility, clinical routine, safety and efficacy were evaluated in a cohort of patients...

  18. 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)

  19. 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.

  20. 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.

  1. 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

  2. Lyophilized allogeneic bone grafts for cystic and discontinuity defects of the jaws

    International Nuclear Information System (INIS)

    Pill Hoon Choung; Eun Seok Kim

    1999-01-01

    Allogenic bone grafts have been used after various processing in each institute was made by lyophilized allogenic bone and used for maxillofacial reconstruction. Three types of lyophilized allogenic bone grafts as powder, chip and block form were performed to reconstruct the following defects: 1) maxillectomy, 2) mandiblectomy, 3) cystectomy, 4) cleft alveolus, 5) gap in orthognathic osteotomy, 6) peri-implant defect, 7) extraction socket, and 8) facial contouring. Above defects can be classified as cystic and discontinuity defects of the maxilia and the mandible. Because discontinuity defects have more difficult problems to reconstruct considering mechanical strength of the allogenic bone. We performed allogenic bone grafts on 50 cystic defects and 12 discontinuity defects of the jaws. Among them, 3 cases were removed due to infection, and the others had no complications. In reconstruction of cystic defects, the defects were filled with allogenic chip which were made from allogenic block bone at the surgery, which later were changed to host bone. Three cases of them showed tooth eruption through the allogenic bone grafting site, changing the eruption pathway, which was interrupted by the lesion. in reconstruction of discontinuity defects, usually allogenic bone has been used as a tray, in which PMCB or demineralized bone chips were filled. But we tried to reconstruct this discontinuity defect using allogeneic bone block without inside filling of PMCB different from tray type. We will present the results of allogenic bone grafts using cranial bone, costochondral graft, and the mandible

  3. Sexual function 1-year after allogeneic hematopoietic stem cell transplantation

    DEFF Research Database (Denmark)

    Noerskov, K. H.; Schjødt, I.; Syrjala, K. L.

    2016-01-01

    Treatment with allogeneic hematopoietic stem cell transplantation (HSCT) is associated with short and long-term toxicities that can result in alterations in sexual functioning. The aims of this prospective evaluation were to determine: (1) associations between HSCT and increased sexual dysfunction...

  4. Soluble urokinase plasminogen activator receptor during allogeneic stem cell transplantation

    DEFF Research Database (Denmark)

    Haastrup, E; Andersen, J; Ostrowski, S R

    2011-01-01

    the course of allogeneic stem cell transplantation (SCT). Twenty SCT patients were included in the study. suPAR was measured by ELISA in daily taken plasma samples during the pretransplant conditioning with chemotherapy and weekly for 1 month after infusion of the graft. suPAR levels before the start...

  5. Single-centre experience of allogeneic haemopoietic stem cell ...

    African Journals Online (AJOL)

    Allogeneic haemopoietic stem cell transplant (Allo-HSCT) is used to treat a broad but well-defined range of paediatric conditions, most frequently in paediatric oncology for treatment intensification or salvage therapy for acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL). Allo-HSCT is also indicated in.

  6. 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.

  7. 'Mini' total body irradiation and allogeneic bone marrow transplantation

    International Nuclear Information System (INIS)

    Gocheva, L.; Sergieva, K.; Koleva, I.; Avramova, V.; Vassileva, V.; Georgieva, S.; Sultanov, B.

    2006-01-01

    Full text: The total body irradiation (TBI) combined with intensive chemotherapy plays an important role in the preparation of patients for bone marrow transplantation (BMT). The first autologous BMT in Bulgaria was performed in 1997 in the Specialized Pediatric Hospital for Active Treatment (SPHAT) of oncohematological diseases. The first TBI, followed by allogeneic BMT, was carried out in 2002 in the 'Queen Giovanna' University Hospital, after which its routine application as a basic form of large field radiotherapy and a main stage of the conditioning regimen for BMT was started. Fourteen allogeneic BMTs including TBI as a basic conditioning regimen have been performed till May 2006. The objective of the present report is to present the first clinical observations in the Bulgarian oncological practice on 'mini' TBI followed by allogeneic blood stem cell transplantation. During the period October 2005 - May 2006, 'mini' TBI followed by allogeneic BMT was carried out for two patients of the age 43 and 50 years. The diagnosis of both patients was acute non-lymphoblastic leukemia, in the remission stage, after one relapse, respectively. Intensive preceding chemotherapy was applied for both patients. A conditioning regimen was applied including the fludarabine purine analogue (3 x 30 mg/m 2 ) and 200 cGy TBI. It was followed by transplantation of allogeneic cell concentrate containing 2.5 x10 6 /kg CD34+ and 4.0 x10 6 /kg CD34+ blood stem cells of partially compatible family donors (a sister and a son), which were tolerable for the patients without complications. Cyclosporine and mycophelonate mofetile were applied as post-transplantation treatment. Active antibiotic, antiviral, symptomatic and substituting therapy, as well as GvHD prophylaxis was applied for both patients. Good clinical tolerance was recorded for the applied low dose conditioning regimen. The patients were discharged within 30 days in good general condition and stable draft action, with

  8. "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…

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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…

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. Allogeneic hematopoietic cell transplantation (allogeneic HCT) for treatment of pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL).

    Science.gov (United States)

    Burke, Michael J; Cao, Qing; Trotz, Barb; Weigel, Brenda; Kumar, Ashish; Smith, Angela; Verneris, Michael R

    2009-12-15

    Allogeneic hematopoietic cell transplant (HCT) with best available donor for children with Philadelphia positive (Ph+) acute lymphoblastic leukemia (ALL) has previously been considered standard practice. Since the introduction of imatinib into the treatment of this disease, the role of allogeneic HCT is more uncertain. We investigated the impact of remission status, graft source, and imatinib use on transplant outcomes for 37 children with Ph+ ALL who received an allogeneic HCT at the University of Minnesota between 1990 and 2006. The median age at HCT was 7.47 (range; 1.4-16.4) years. Thirteen patients received imatinib therapy pre- and/or post-HCT (imatinib group) and 24 patients, received either no imatinib (n = 23) or only post-HCT relapse (n = 1) (non-imatinib group). There was no difference in disease-free survival (DFS) or relapse between the imatinib and non-imatinib groups at 3 years (62%/15% vs. 53%/26%; P = 0.99; 0.81, respectively). There was no significant difference in transplant outcomes between matched related donor or unrelated donor (umbilical cord blood or matched unrelated marrow) recipients whereas patients receiving allogeneic HCT in first remission (CR1) had superior DFS and less relapse compared to patients transplanted in >or=CR2 (71%/16% vs. 29%/36%; P = 0.01; P = 0.05). Based on this retrospective analysis at a single institution, the use of imatinib either pre- and/or post-transplant does not appear to significantly impact outcomes for children with Ph+ ALL and allogeneic HCT with the best available donor should be encouraged in CR1.

  2. Radiations

    International Nuclear Information System (INIS)

    Pujol Mora, J.

    1999-01-01

    The exposition to ionizing radiations is a constant fact in the life of the human being and its utilization as diagnostic and therapeutic method is generalized. However, it is notorious how as years go on, the fear to the ionizing radiation seems to persist too, and this fact is not limited to the common individual, but to the technical personnel and professional personnel that labors with them same. (S. Grainger) [es

  3. Radiation

    International Nuclear Information System (INIS)

    Davidson, J.H.

    1986-01-01

    The basic facts about radiation are explained, along with some simple and natural ways of combating its ill-effects, based on ancient healing wisdom as well as the latest biochemical and technological research. Details are also given of the diet that saved thousands of lives in Nagasaki after the Atomic bomb attack. Special comment is made on the use of radiation for food processing. (U.K.)

  4. Pelvic reconstruction with allogeneic bone graft after tumor resection

    Science.gov (United States)

    Wang, Wei; Bi, Wen Zhi; Yang, Jing; Han, Gang; Jia, Jin Peng

    2013-01-01

    OBJECTIVES : Pelvic reconstruction after tumor resection is challenging. METHODS: A retrospective study had been preformed to compare the outcomes among patients who received pelvic reconstructive surgery with allogeneic bone graft after en bloc resection of pelvic tumors and patients who received en bloc resection only. RESULTS: Patients without reconstruction had significantly lower functional scores at 3 months (10 vs. 15, P = 0.001) and 6 months after surgery (18.5 vs. 22, P = 0.0024), a shorter duration of hospitalization (16 day vs. 40 days, P 0.05). CONCLUSIONS : Pelvic reconstruction with allogeneic bone graft after surgical management of pelvic tumors is associated with satisfactory surgical and functional outcomes. Further clinical studies are required to explore how to select the best reconstruction method. Level of Evidence IV, Case Series. PMID:24453659

  5. 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...

  6. Radiation

    International Nuclear Information System (INIS)

    Winther, J.F.; Ulbak, K.; Dreyer, L.; Pukkala, E.; Oesterlind, A.

    1997-01-01

    Exposure to solar and ionizing radiation increases the risk for cancer in humans. Some 5% of solar radiation is within the ultraviolet spectrum and may cause both malignant melanoma and non-melanocytic skin cancer; the latter is regarded as a benign disease and is accordingly not included in our estimation of avoidable cancers. Under the assumption that the rate of occurrence of malignant melanoma of the buttocks of both men and women and of the scalp of women would apply to all parts of the body in people completely unexposed to solar radiation, it was estimated that approximately 95% of all malignant melanomas arising in the Nordic populations around the year 2000 will be due to exposure to natural ultraviolet radiation, equivalent to an annual number of about 4700 cases, with 2100 in men and 2600 in women, or some 4% of all cancers notified. Exposure to ionizing radiation in the Nordic countries occurs at an average effective dose per capita per year of about 3 mSv (Iceland, 1.1 mSv) from natural sources, and about 1 mSv from man-made sources. While the natural sources are primarily radon in indoor air, natural radionuclides in food, cosmic radiation and gamma radiation from soil and building materials, the man-made sources are dominated by the diagnostic and therapeutic use of ionizing radiation. On the basis of measured levels of radon in Nordic dwellings and associated risk estimates for lung cancer derived from well-conducted epidemiological studies, we estimated that about 180 cases of lung cancer (1% of all lung cancer cases) per year could be avoided in the Nordic countries around the year 2000 if indoor exposure to radon were eliminated, and that an additional 720 cases (6%) could be avoided annually if either radon or tobacco smoking were eliminated. Similarly, it was estimated that the exposure of the Nordic populations to natural sources of ionizing radiation other than radon and to medical sources will each give rise to an annual total of 2120

  7. Financial burden in recipients of allogeneic hematopoietic cell transplantation.

    Science.gov (United States)

    Khera, Nandita; Chang, Yu-hui; Hashmi, Shahrukh; Slack, James; Beebe, Timothy; Roy, Vivek; Noel, Pierre; Fauble, Veena; Sproat, Lisa; Tilburt, Jon; Leis, Jose F; Mikhael, Joseph

    2014-09-01

    Although allogeneic hematopoietic cell transplantation (HCT) is an expensive treatment for hematological disorders, little is known about the financial consequences for the patients who undergo this procedure. We analyzed factors associated with its financial burden and its impact on health behaviors of allogeneic HCT recipients. A questionnaire was retrospectively mailed to 482 patients who underwent allogeneic HCT from January 2006 to June 2012 at the Mayo Clinic, to collect information regarding current financial concerns, household income, employment, insurance, out-of-pocket expenses, and health and functional status. A multivariable logistic regression analysis identified factors associated with financial burden and treatment nonadherence. Of the 268 respondents (56% response rate), 73% reported that their sickness had hurt them financially. All patients for whom the insurance information was available (missing, n = 13) were insured. Forty-seven percent of respondents experienced financial burden, such as household income decreased by >50%, selling/mortgaging home, or withdrawing money from retirement accounts. Three percent declared bankruptcy. Younger age and poor current mental and physical functioning increased the likelihood of financial burden. Thirty-five percent of patients reported deleterious health behaviors because of financial constraints. These patients were likely to be younger, have lower education, and with a longer time since HCT. Being employed decreased the likelihood of experiencing financial burden and treatment nonadherence due to concern about costs. A significant proportion of allogeneic HCT survivors experience financial hardship despite insurance coverage. Future research should investigate potential interventions to help at-risk patients and prevent adverse financial outcomes after this life-saving procedure. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  8. Delayed allogeneic skin graft rejection in CD26-deficient mice.

    Science.gov (United States)

    Zhao, Xiangli; Zhang, Kai; Daniel, Peter; Wisbrun, Natali; Fuchs, Hendrik; Fan, Hua

    2018-03-23

    Organ transplantation is an effective therapeutic tool for treating many terminal diseases. However, one of the biggest challenges of transplantation is determining how to achieve the long-term survival of the allogeneic or xenogeneic transplant by, for example, preventing transplant rejection. In the current study, CD26 gene-knockout mice were used to investigate the potential role of CD26/dipeptidyl peptidase-4 (DPPIV) in allogeneic skin graft rejection by tail-skin transplantation. Compared with wild-type (CD26 +/+ ) counterparts, CD26 -/- mice showed reduced necrosis of grafts and delayed graft rejection after skin transplantation. Concentrations of serum IgG, including its subclasses IgG1 and IgG2a, were significantly reduced in CD26 -/- mice during graft rejection. Moreover, after allogeneic skin transplantation, the secretion levels of the cytokines IFN-γ, IL-2, IL-6, IL-4, and IL-13 were significantly reduced, whereas the level of the cytokine IL-10 was increased in the serum of CD26 -/- mice compared with that in the serum of CD26 +/+ mice. Additionally, the concentration of IL-17 in serum and the percentage of cells secreting IL-17 in mouse peripheral blood lymphocytes (MPBLs) were both significantly lower, while the percentage of regulatory T cells (Tregs) was significantly higher in MPBLs of CD26 -/- mice than in those of CD26 +/+ mice. Furthermore, a lower percentage of CD8 + T cells in MPBLs and fewer infiltrated macrophages and T cells in graft tissues of CD26 -/- mice were detected during graft rejection. These results indicate that CD26 is involved in allogeneic skin graft rejection and provides another hint that CD26 deficiency leads to less rejection due to lower activation and proliferation of host immune cells.

  9. Allogeneic stem cell transplantation in acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Natasha Ali

    2012-11-01

    Full Text Available We report a case series of 12 patients with acute myeloid leukemia who underwent allogeneic stem cell transplant with a matched related donor. Male to female ratio was 1:1. The main complication post-transplant was graft-versus-host disease (n=7 patients. Transplant-related mortality involved one patient; cause of death was multi-organ failure. After a median follow up of 36.0±11.3 months, overall survival was 16%.

  10. Rabbit articular cartilage defects treated by allogenic chondrocyte transplantation

    OpenAIRE

    Boopalan, P. R. J. V. C.; Sathishkumar, Solomon; Kumar, Senthil; Chittaranjan, Samuel

    2006-01-01

    Articular cartilage defects have a poor capacity for repair. Most of the current treatment options result in the formation of fibro-cartilage, which is functionally inferior to normal hyaline articular cartilage. We studied the effectiveness of allogenic chondrocyte transplantation for focal articular cartilage defects in rabbits. Chondrocytes were cultured in vitro from cartilage harvested from the knee joints of a New Zealand White rabbit. A 3 mm defect was created in the articular cartilag...

  11. Chimeric autologous/allogeneic constructs for skin regeneration.

    Science.gov (United States)

    Rasmussen, Cathy Ann; Tam, Joshua; Steiglitz, Barry M; Bauer, Rebecca L; Peters, Noel R; Wang, Ying; Anderson, R Rox; Allen-Hoffmann, B Lynn

    2014-08-01

    The ideal treatment for severe cutaneous injuries would eliminate the need for autografts and promote fully functional, aesthetically pleasing autologous skin regeneration. NIKS progenitor cell-based skin tissues have been developed to promote healing by providing barrier function and delivering wound healing factors. Independently, a device has recently been created to "copy" skin by harvesting full-thickness microscopic tissue columns (MTCs) in lieu of autografts traditionally harvested as sheets. We evaluated the feasibility of combining these two technologies by embedding MTCs in NIKS-based skin tissues to generate chimeric autologous/allogeneic constructs. Chimeric constructs have the potential to provide immediate wound coverage, eliminate painful donor site wounds, and promote restoration of a pigmented skin tissue possessing hair follicles, sweat glands, and sebaceous glands. After MTC insertion, chimeric constructs and controls were reintroduced into air-interface culture and maintained in vitro for several weeks. Tissue viability, proliferative capacity, and morphology were evaluated after long-term culture. Our results confirmed successful MTC insertion and integration, and demonstrated the feasibility of generating chimeric autologous/allogeneic constructs that preserved the viability, proliferative capacity, and structure of autologous pigmented skin. These feasibility studies established the proof-of-principle necessary to further develop chimeric autologous/allogeneic constructs for the treatment of complex skin defects. Reprint & Copyright © 2014 Association of Military Surgeons of the U.S.

  12. Clinical Allogeneic and Autologous Islet Cell Transplantation: Update

    Directory of Open Access Journals (Sweden)

    Shinichi Matsumoto

    2011-06-01

    Full Text Available Islet cell transplantation is categorized as a β-cell replacement therapy for diabetic patients who lack the ability to secrete insulin. Allogeneic islet cell transplantation is for the treatment of type 1 diabetes, and autologous islet cell transplantation is for the prevention of surgical diabetes after a total pancreatectomy. The issues of allogeneic islet cell transplantation include poor efficacy of islet isolation, the need for multiple donor pancreata, difficulty maintaining insulin independence and undesirable side effects of immunosuppressive drugs. Those issues have been solved step by step and allogeneic islet cell transplantation is almost ready to be the standard therapy. The donor shortage will be the next issue and marginal and/or living donor islet cell transplantation might alleviate the issue. Xeno-islet cell transplantation, β-cell regeneration from human stem cells and gene induction of the naïve pancreas represent the next generation of β-cell replacement therapy. Autologous islet cell transplantation after total pancreatectomy for the treatment of chronic pancreatitis with severe abdominal pain is the standard therapy, even though only limited centers are able to perform this treatment. Remote center autologous islet cell transplantation is an attractive option for hospitals performing total pancreatectomies without the proper islet isolation facilities.

  13. Allogeneic Mesenchymal Stem Cell Treatment Induces Specific Alloantibodies in Horses

    Directory of Open Access Journals (Sweden)

    Sean D. Owens

    2016-01-01

    Full Text Available Background. It is unknown whether horses that receive allogeneic mesenchymal stem cells (MSCs injections develop specific humoral immune response. Our goal was to develop and validate a flow cytometric MSC crossmatch procedure and to determine if horses that received allogeneic MSCs in a clinical setting developed measurable antibodies following MSC administration. Methods. Serum was collected from a total of 19 horses enrolled in 3 different research projects. Horses in the 3 studies all received unmatched allogeneic MSCs. Bone marrow (BM or adipose tissue derived MSCs (ad-MSCs were administered via intravenous, intra-arterial, intratendon, or intraocular routes. Anti-MSCs and anti-bovine serum albumin antibodies were detected via flow cytometry and ELISA, respectively. Results. Overall, anti-MSC antibodies were detected in 37% of the horses. The majority of horses (89% were positive for anti-bovine serum albumin (BSA antibodies prior to and after MSC injection. Finally, there was no correlation between the amount of anti-BSA antibody and the development of anti-MSC antibodies. Conclusion. Anti allo-MSC antibody development was common; however, the significance of these antibodies is unknown. There was no correlation between either the presence or absence of antibodies and the percent antibody binding to MSCs and any adverse reaction to a MSC injection.

  14. Reduction in requirements for allogeneic blood products: nonpharmacologic methods.

    Science.gov (United States)

    Hardy, J F; Bélisle, S; Janvier, G; Samama, M

    1996-12-01

    Various strategies have been proposed to decrease bleeding and allogeneic transfusion requirements during and after cardiac operations. This article attempts to document the usefulness, or lack thereof, of the nonpharmacologic methods available in clinical practice. Blood conservation methods were reviewed in chronologic order, as they become available to patients during the perisurgical period. The literature in support of or against each strategy was reexamined critically. Avoidance of preoperative anemia and adherence to published guidelines for the practice of transfusion are of paramount importance. Intraoperatively, tolerance of low hemoglobin concentrations and use of autologous blood (predonated or harvested before bypass) will reduce allogeneic transfusions. The usefulness of plateletpheresis and retransfusion of shed mediastinal fluid remains controversial. Intraoperatively and postoperatively, maintenance of normothermia contributes to improved hemostasis. Several approaches have been shown to be effective. An efficient combination of methods can reduce, and sometimes abolish, the need for allogeneic blood products after cardiac operations, inasmuch as all those involved in the care of cardiac surgical patients adhere thoughtfully to existing transfusion guidelines.

  15. 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

  16. A new method of prefabricated vascularized allogenic bone grafts for maxillo-mandibular reconstruction

    International Nuclear Information System (INIS)

    Pill-Hoon Choung

    1999-01-01

    Although there are various applications of allogenic bone grafts, a new technique of prevascularized lyophilized allogenic bone grafting for maxillo-mandibular reconstruction will be presented. Allogenic bone has been made by author's protocol for jaw defects as a powder, chip or block bone type. The author used lyophilized allogenic bone grafts for discontinuity defects as a block bone. In those cases, neovascularization and resorption of the allogenic bone were important factors for success of grafting. To overcome the problems, the author designed the technique of prefabricated vascularization of allogenic bone, which was lyophilized cranium, with an application of bovine BMP or not. Lyophilized cranial bone was designed for the defects and was put into the scalp. After confirming a hot spot via scintigram several months later, vascularized allogenic bone was harvested pedicled on the parietotemporal fascia based on the superficial temporal artery and vein. Vascularized allogenic cranial bone was rotated into the defect and fixed rigidly. Postoperatively, there was no severe resorption and functional disturbance of the mandible. In this technique, BMP seems to be an important role to help osteogenesis and neovascularization. Eight patients underwent prefabricated vascularization of allogenic bone grafts. Among them, four cases of reconstruction in mandibular discontinuity defects and one case of reconstruction in maxillectomy defect underwent this method, which will be presented with good results. This method may be an alternative technique of microvascular free bone graft

  17. Allogeneic bone marrow grafts in genotyped swine

    International Nuclear Information System (INIS)

    Vaiman, M.

    1974-01-01

    The proof of a major histocompatibility complex (MHC) called SL-A enabled to promote bone marrow allografts. A study of the response to that kind of graft in irradiated pig states a number of interesting points. Bone marrow allografting complies with the rule of tissular compatibility with the major histocompatibility complex. The taking of SL-A incompatible bone marrow allografts could not be achieved under the experimental conditions. In spite of the high doses of radiation, 950 to 1050 rads, higher than 1.5 LD 100%, recipients were capable of rejecting their grafts, regularly. SL-A identify ensured 100%, initial achievement. However, animals developed regular fatal disease within a fairly short time. This development could by no means, be ascribed to the sole sequealae of radiation sickness since autografted animals at equal or even higher doses, showed none of the symptome. Assumption of a chronic graft-vs-host reactions, induced by the minor histocompatible systems, was put foreward, but should be confirmed histopathologically [fr

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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 ...

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. Antigen recognition by MHC-incompatible cells of a human mismatched chimera

    NARCIS (Netherlands)

    Roncarolo, M. G.; Yssel, H.; Touraine, J. L.; Bacchetta, R.; Gebuhrer, L.; de Vries, J. E.; Spits, H.

    1988-01-01

    Tetanus toxin (TT)-specific T cell clones of donor origin were obtained from a patient with severe combined immunodeficiency (SCID) successfully reconstituted by transplantation of allogeneic fetal liver and thymus cells from two different donors performed 10 yr ago. A series of these clones

  1. 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...

  2. RENAL ALLOGENEIC TRANSPLANTATION IN PATIENT WITH HAEMOPHILIA B

    Directory of Open Access Journals (Sweden)

    N. V. Purlo

    2014-01-01

    Full Text Available We report the case of successful renal allogeneic transplantation and treatment in a 56-year-old patient with haemophilia B at Hematology Research Center. He has received replacement therapy by factor IX since 2010. The transplant is marked with good renal function during 13 post-transplant months without episodes of rejection or bleeding complications. The complicated surgical interventions are possible in patients with haemophilia В аnd end-stage chronic renal failure in the presence of replacement therapy of IX factor for the purpose of achievement of optimum hemostasis.

  3. 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.

  4. Bronchiolitis obliterans syndrome after allogeneic hematopoietic SCT: phenotypes and prognosis.

    Science.gov (United States)

    Bergeron, A; Godet, C; Chevret, S; Lorillon, G; Peffault de Latour, R; de Revel, T; Robin, M; Ribaud, P; Socié, G; Tazi, A

    2013-06-01

    Bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic SCT (HSCT) is recognized as a new-onset obstructive lung defect (OLD) in pulmonary function testing and is related to pulmonary chronic GVHD. Little is known about the different phenotypes of patients with BOS and their outcomes. We reviewed the data of all allogeneic HSCT recipients referred to our pulmonary department for a non-infectious bronchial disease between 1999 and 2010. We identified 103 patients (BOS (n=77), asthma (n=11) and chronic bronchitis (n=15)). In patients with BOS, we identified two functional phenotypes: a typical OLD, that is, forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio <0.7 (n=53), and an atypical OLD with a concomitant decrease in the FEV1 <80% and FVC <80% predicted with a normal total lung capacity (n=24). The typical OLD was characterized by more severe FEV1 and fewer centrilobular nodules on the computed tomography scan. The FEV1 was not significantly affected during the follow-up, regardless of the phenotype. In addition to acute and extensive chronic GVHD, only the occurrence of BOS soon after transplantation and the intentional treatment of BOS with steroids were associated with a poor survival. The determination of patient subgroups should be explored to improve the management of this condition.

  5. Central nervous system infection following allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Hanajiri, Ryo; Kobayashi, Takeshi; Yoshioka, Kosuke; Watanabe, Daisuke; Watakabe, Kyoko; Murata, Yutaka; Hagino, Takeshi; Seno, Yasushi; Najima, Yuho; Igarashi, Aiko; Doki, Noriko; Kakihana, Kazuhiko; Sakamaki, Hisashi; Ohashi, Kazuteru

    2017-03-01

    Here, we described the clinical characteristics and outcomes of central nervous system (CNS) infections occurring after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in a single institution over the previous 6 years. Charts of 353 consecutive allogeneic transplant recipients were retrospectively reviewed for CNS infection. A total of 17 cases of CNS infection were identified at a median of 38 days (range, 10-1028 days) after allo-HSCT. Causative pathogens were human herpesvirus-6 (n=6), enterococcus (n=2), staphylococcus (n=2), streptococcus (n=2), varicella zoster virus (n=1), cytomegalovirus (n=1), John Cunningham virus (n=1), adenovirus (n=1), and Toxoplasma gondii (n=1). The cumulative incidence of CNS infection was 4.1% at 1 year and 5.5% at 5 years. Multivariate analysis revealed that high-risk disease status was a risk factor for developing CNS infection (p=.02), and that overall survival at 3 years after allo-HSCT was 33% in patients with CNS infection and 53% in those without CNS infection (p=.04). Copyright © 2016 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.

  6. Endocrinopathies after Allogeneic and Autologous Transplantation of Hematopoietic Stem Cells

    Directory of Open Access Journals (Sweden)

    Francesco Orio

    2014-01-01

    Full Text Available Early and late endocrine disorders are among the most common complications in survivors after hematopoietic allogeneic- (allo- and autologous- (auto- stem cell transplant (HSCT. This review summarizes main endocrine disorders reported in literature and observed in our center as consequence of auto- and allo-HSCT and outlines current options for their management. Gonadal impairment has been found early in approximately two-thirds of auto- and allo-HSCT patients: 90–99% of women and 60–90% of men. Dysfunctions of the hypothalamus-pituitary-growth hormone/insulin growth factor-I axis, hypothalamus-pituitary-thyroid axis, and hypothalamus-pituitary-adrenal axis were documented as later complicances, occurring in about 10, 30, and 40–50% of transplanted patients, respectively. Moreover, overt or subclinical thyroid complications (including persistent low-T3 syndrome, chronic thyroiditis, subclinical hypo- or hyperthyroidism, and thyroid carcinoma, gonadal failure, and adrenal insufficiency may persist many years after HSCT. Our analysis further provides evidence that main recognized risk factors for endocrine complications after HSCT are the underlying disease, previous pretransplant therapies, the age at HSCT, gender, total body irradiation, posttransplant derangement of immune system, and in the allogeneic setting, the presence of graft-versus-host disease requiring prolonged steroid treatment. Early identification of endocrine complications can greatly improve the quality of life of long-term survivors after HSCT.

  7. 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...

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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...

  15. 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.

  16. Allogenic blood transfusion following total hip arthroplasty: results from the nationwide inpatient sample, 2000 to 2009.

    Science.gov (United States)

    Saleh, Anas; Small, Travis; Chandran Pillai, Aiswarya Lekshmi Pillai; Schiltz, Nicholas K; Klika, Alison K; Barsoum, Wael K

    2014-09-17

    The large-scale utilization of allogenic blood transfusion and its associated outcomes have been described in critically ill patients and those undergoing high-risk cardiac surgery but not in patients undergoing elective total hip arthroplasty. The objective of this study was to determine the trends in utilization and outcomes of allogenic blood transfusion in patients undergoing primary total hip arthroplasty in the United States from 2000 to 2009. An observational cohort of 2,087,423 patients who underwent primary total hip arthroplasty from 2000 to 2009 was identified in the Nationwide Inpatient Sample. International Classification of Diseases, Ninth Revision, Clinical Modification procedure codes 99.03 and 99.04 were used to identify patients who received allogenic blood products during their hospital stay. Risk factors for allogenic transfusions were identified with use of multivariable logistic regression models. We used propensity score matching to estimate the adjusted association between transfusion and surgical outcomes. The rate of allogenic blood transfusion increased from 11.8% in 2000 to 19.0% in 2009. Patient-related risk factors for receiving an allogenic blood transfusion include an older age, female sex, black race, and Medicaid insurance. Hospital-related risk factors include rural location, smaller size, and non-academic status. After adjusting for confounders, allogenic blood transfusion was associated with a longer hospital stay (0.58 ± 0.02 day; p conservation methods. Copyright © 2014 by The Journal of Bone and Joint Surgery, Incorporated.

  17. Allogeneic CD19-CAR-T cell infusion after allogeneic hematopoietic stem cell transplantation in B cell malignancies.

    Science.gov (United States)

    Liu, Jun; Zhong, Jiang F; Zhang, Xi; Zhang, Cheng

    2017-01-31

    Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered the cornerstone in treatment of hematological malignancies. However, relapse of the hematological disease after allo-HSCT remains a challenge and is associated with poor long-term survival. Chimeric antigen receptor redirected T cells (CAR-T cells) can lead to disease remission in patients with relapsed/refractory hematological malignancies. However, the therapeutic window for infusion of CAR-T cells post allo-HSCT and its efficacy are debatable. In this review, we first discuss the use of CAR-T cells for relapsed cases after allo-HSCT. We then review the toxicities and the occurrence of graft-versus-host disease in relapsed patients who received CAR-T cells post allo-HSCT. Finally, we review clinical trial registrations and the therapeutic time window for infusion of CAR-T cells post allo-HSCT. The treatment of allogeneic CAR-T cells is beneficial for patients with relapsed B cell malignancies after allo-HSCT with low toxicities and complications. However, multicenter clinical trials with larger sample sizes should be performed to select the optimal therapeutic window and confirm its efficacy.

  18. 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.

  19. 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.

  20. Value of liver elastography and abdominal ultrasound for detection of complications of allogeneic hemopoietic SCT.

    Science.gov (United States)

    Karlas, T; Weber, J; Nehring, C; Kronenberger, R; Tenckhoff, H; Mössner, J; Niederwieser, D; Tröltzsch, M; Lange, T; Keim, V

    2014-06-01

    Hepatic complications contribute to morbidity and mortality after allogeneic hemopoietic SCT. Liver Doppler ultrasound and elastography represent promising methods for pretransplant risk assessment and early detection of complications. Ultrasound (liver and spleen size, liver perfusion) and elastography (transient elastography (TE); right liver lobe acoustic radiation force impulse imaging (r-ARFI); left liver lobe ARFI (l-ARFI)) were prospectively evaluated in patients with indications for allo-SCT. Measurements were performed before and repeatedly after SCT. Results were compared with the incidence of life-threatening complications and death during the first 150 days after SCT. Of 59 included patients, 16 suffered from major complications and 9 of them died within the follow-up period. At baseline, liver and spleen size, liver perfusion, TE and r-ARFI did not differ significantly between patients with and without severe complications. In contrast, l-ARFI was significantly elevated in patients who later developed severe complications (1.58±0.30 m/s vs 1.37±0.27 m/s, P=0.030). After SCT, l-ARFI values remained elevated and TE showed increasing liver stiffness in patients with complications. The value of conventional liver ultrasound for prediction of severe SCT complications is limited. Increased values for TE and l-ARFI are associated with severe SCT complications and demand further evaluation.

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. G-CSF-primed BM for allogeneic SCT: revisited.

    Science.gov (United States)

    Pessach, I; Resnick, I; Shimoni, A; Nagler, A

    2015-07-01

    G-SCF-mobilized PBSC (GPB) grafts have a higher cell dose and somewhat more committed progenitor cells than steady-state BM (SBM), resulting in faster engraftment and faster immunological reconstitution. On the other hand, transplant related mortality (TRM), disease-free survival (DFS) and overall survival (OS) are similar both for PB and for BM. In contrast to SBM, G-CSF-primed BM (GBM) grafts stimulate HSC proliferation, increasing cell dose and thus resulting in faster engraftment because of higher cell dose infused, or because of treatment with G-CSF. Furthermore, GBM may induce tolerance and functional modulations in donor hematopoiesis and immunity, further reducing GVHD incidence, which is already lower with SBM compared with GPB grafts. Overall, a growing body of clinical evidence suggests that GBM transplants may share the advantages of GPB transplantations, without the associated increased risk of GVHD, and might be an attractive graft source for allogeneic SCTs.

  8. How and when I do allogeneic transplant in CLL.

    Science.gov (United States)

    Gribben, John G

    2018-05-11

    Allogenic stem cell transplantation (allo-SCT) has been considered the treatment of choice for high-risk patients with chronic lymphocytic leukemia (CLL) and the only approach offered with curative intent in this disease. The availability novel agents including the B cell receptor inhibitors (BCRi) ibrutinib, acalabrutinib and idelalisib, as well as venetoclax which targets the BCL2 pathway and the success of these agents in treating high-risk disease patients has made it more difficult to assess who and when in their treatment course allo-SCT should be considered. In this review, I will discuss the different treatment options available for the treatment of high-risk CLL and how allo-SCT fits into the treatment algorithm in the era of novel agents. Copyright © 2018 American Society of Hematology.

  9. Immune Reconstitution after Allogeneic Hematopoietic Stem Cell Transplantation

    Science.gov (United States)

    Ogonek, Justyna; Kralj Juric, Mateja; Ghimire, Sakhila; Varanasi, Pavankumar Reddy; Holler, Ernst; Greinix, Hildegard; Weissinger, Eva

    2016-01-01

    The timely reconstitution and regain of function of a donor-derived immune system is of utmost importance for the recovery and long-term survival of patients after allogeneic hematopoietic stem cell transplantation (HSCT). Of note, new developments such as umbilical cord blood or haploidentical grafts were associated with prolonged immunodeficiency due to delayed immune reconstitution, raising the need for better understanding and enhancing the process of immune reconstitution and finding strategies to further optimize these transplant procedures. Immune reconstitution post-HSCT occurs in several phases, innate immunity being the first to regain function. The slow T cell reconstitution is regarded as primarily responsible for deleterious infections with latent viruses or fungi, occurrence of graft-versus-host disease, and relapse. Here we aim to summarize the major steps of the adaptive immune reconstitution and will discuss the importance of immune balance in patients after HSCT. PMID:27909435

  10. Allogeneic epidermal substitutes in the treatment of chronic diabetic leg and foot ulcers

    Directory of Open Access Journals (Sweden)

    Andrea Marchesi

    2014-09-01

    Full Text Available Aim: Diabetic foot ulcers are the most common cause of nontraumatic lower extremity amputations in the industrialized world. Tissue-engineering products offer a lower extremity salvage strategy when healing does not proceed according to the standard of care. New allogeneic sheets are available for the management of diabetic leg and foot ulcers. Methods: The endpoints of this case series study regard preliminary outcomes of the application of allogeneic keratinocytes composed of benzyl ester of hyaluronic acid to 16 diabetic foot and leg ulcers in 11 patients with type 2 diabetes mellitus. Results: Between 21 and 70 days after cellular therapy, 6 out of 16 lesions were completely healed, reducing the wound dimension by 70% and improving the wound bed score by 52%. Conclusion: The clinical results of the new allogeneic sheets indicate that allogeneic keratinocytes may represent an effective and safe therapy for diabetic foot and leg ulcers in the multidisciplinary approach to this diabetes-related complication.

  11. Current status of grafts and implants in rhinoplasty: Part II. Homologous grafts and allogenic implants.

    Science.gov (United States)

    Sajjadian, Ali; Naghshineh, Nima; Rubinstein, Roee

    2010-03-01

    After reading this article, the participant should be able to: 1. Understand the challenges in restoring volume and structural integrity in rhinoplasty. 2. Identify the appropriate uses of various homologous grafts and allogenic implants in reconstruction, including: (a) freeze-dried acellular allogenic cadaveric dermis grafts, (b) irradiated cartilage grafts, (c) hydroxyapatite mineral matrix, (d) silicone implants, (e) high-density polyethylene implants, (f) polytetrafluoroethylene implants, and (g) injectable filler materials. 3. Identify the advantages and disadvantages of each of these biomaterials. 4. Understand the specific techniques that may aid in the use these grafts or implants. This review specifically addresses the use of homologous grafts and allogenic implants in rhinoplasty. It is important to stress that autologous materials remain the preferred graft material for use in rhinoplasty, owing to their high biocompatibility and low risk of infection and extrusion. However, concerns of donor-site morbidity, graft availability, and graft resorption have motivated the development and use of homologous and allogenic implants.

  12. Alternative allogeneic donor sources for transplantation for childhood diseases: unrelated cord blood and haploidentical family donors.

    Science.gov (United States)

    Cairo, Mitchell S; Rocha, Vanderson; Gluckman, Eliane; Hale, Gregory; Wagner, John

    2008-01-01

    Allogeneic stem cell transplantation has been demonstrated to be curative in a wide variety of pediatric malignant and nonmalignant diseases, and can be traced back over 50 years ago to the original report of Thomas et al. HLA matched sibling donors have been the gold standard for pediatric recipients requiring allogeneic donors for both nonmalignant and malignant conditions. However, only 25% of potential pediatric recipients possesses an HLA-matched sibling donor, and the frequency is even less in those with genetic nonmalignant conditions because of genetically affected other siblings within the family. Therefore, 75% to 90% of potential pediatric recipients require alternative allogeneic donor cells for treatment of their underlying conditions. Potential alternative allogeneic donor sources include unrelated cord blood donors, unrelated adult donors, and haploidentical family donors. In this article we review the experience of both unrelated cord blood donor and haploidentical family donor transplants in selected pediatric malignant and nonmalignant conditions.

  13. Socially disadvantaged parents of children treated with allogeneic haematopoietic stem cell transplantation (HSCT)

    DEFF Research Database (Denmark)

    Larsen, Hanne Bækgaard; Heilmann, Carsten; Johansen, Christoffer

    2013-01-01

    PURPOSE: This study was undertaken to test a daily Family Navigator Nurse (FNN) conducted intervention program, to support parents during the distressful experience of their child's Allogeneic Haematopoietic Stem Cell Transplantation (HSCT). METHODS: A qualitative analysis of the supportive...

  14. Comparison of immune reconstitution after allogeneic vs. autologous stem cell transplantation in 182 pediatric recipients

    Directory of Open Access Journals (Sweden)

    V. Wiegering

    2017-03-01

    Conclusion: Children undergoing a HSCT show a different pattern of immune reconstitution in the allogeneic and autologous setting. This might influence the outcome and should affect the clinical handling of infectious prophylaxis and re-vaccinations.

  15. Histone deacetylase inhibition regulates inflammation and enhances Tregs after allogeneic hematopoietic cell transplantation in humans

    NARCIS (Netherlands)

    Choi, S.W.; Gatza, E.; Hou, G.; Sun, Y; Whitfield, J.; Song, Y.; Oravecz-Wilson, K.; Tawara, I.; Dinarello, C.A.; Reddy, P.

    2015-01-01

    We examined immunological responses in patients receiving histone deacetylase (HDAC) inhibition (vorinostat) for graft-versus-host disease prophylaxis after allogeneic hematopoietic cell transplant. Vorinostat treatment increased histone acetylation in peripheral blood mononuclear cells (PBMCs) from

  16. 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

  17. 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

  18. 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...

  19. Second myeloablative allogeneic stem cell transplantation (SCT) using cord blood for leukemia relapsed after initial allogeneic SCT.

    Science.gov (United States)

    Konuma, Takaaki; Ooi, Jun; Takahashi, Satoshi; Tomonari, Akira; Tsukada, Nobuhiro; Kato, Seiko; Sato, Aki; Monma, Fumihiko; Kasahara, Senji; Uchimaru, Kaoru; Iseki, Tohru; Tojo, Arinobu; Asano, Shigetaka

    2009-06-01

    There are many reports of second allogeneic stem cell transplantation (allo-SCT) using cord blood (CB) for graft failure after initial allo-SCT. However, the efficacy of second allo-SCT using CB for patients with leukemia relapsed after initial allo-SCT is unknown. We report the results of second allo-SCT using CB in seven adult patients with leukemia relapsed after initial allo-SCT. All patients received a myeloablative conditioning regimen including oral busulfan 16 mg/kg, intravenously fludarabine 100mg/m(2) and cyclophosphamide 120 mg/kg. All but one patient had myeloid reconstitution and four patients remain alive at between 4 and 40 months after second SCT. We conclude that second myeloablative allo-SCT using CB may be feasible in selected patients with the relatively younger age, less organ damage and longer time interval between first and second allo-SCT.

  20. Comparative analysis of autologous blood transfusion and allogeneic blood transfusion in surgical patients

    OpenAIRE

    Long, Miao-Yun; Liu, Zhong-Han; Zhu, Jian-Guang

    2014-01-01

    Objective: To investigate application effects of autologous blood transfusion and allogeneic blood transfusion in surgically treated patients receiving spine surgery, abdomen surgery and ectopic pregnancy surgery. Methods: 130 patients who would undergo selective operations were divided into autologous transfusion group and allogeneic transfusion group. Both groups received the same anesthesia, and there was no significant difference in transfusion volume or fluid infusion volume. Results: Th...

  1. Achieving an early pregnancy following allogeneic uterine transplantation in a rabbit model

    OpenAIRE

    Saso, Srdjan; Petts, Gemma; David, Anna L.; Thum, Meen-Yau; Chatterjee, Jayanta; Vicente Antón, José Salvador; Marco Jiménez, Francisco; Corless, David; Boyd, Michael; Noakes, David; Lindsay, Iain; Del Priorei, Giuseppe; Ghaem-Maghami, Sadaf; Smith, J. Richard

    2015-01-01

    [EN] Objective: Uterine transplantation (UTx) has been proposed as a treatment option for women diagnosed with absolute uterine factor infertility (AUFI). The goal of UTx remains achieving pregnancy and live birth of a healthy neonate following allogeneic UTx. Our aim was to assess whether fertility was possible following allogeneic uterine transplantation (UTx), when the recipient had demonstrated long-term survival and had been administered immunosuppression. Study desig...

  2. Establishment of donor Chimerism Using Allogeneic Bone Marrow with AMP Cell Co-infusion

    Science.gov (United States)

    2017-09-01

    AWARD NUMBER: W81XWH-15-1-0234 TITLE: Establishment of donor Chimerism Using Allogeneic Bone Marrow with AMP Cell Co-infusion PRINCIPAL...14/2017 4. TITLE AND SUBTITLE Establishment of donor Chimerism Using Allogeneic Bone Marrow with AMP Cell Co-infusion 5a. CONTRACT NUMBER 5b. GRANT...tolerance induction of all types of allografts. In this study, we investigate whether co-infusion of amnion- derived multipotent progenitor (AMP) cells

  3. 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

  4. Ceacam1 separates graft-versus-host-disease from graft-versus-tumor activity after experimental allogeneic bone marrow transplantation.

    Directory of Open Access Journals (Sweden)

    Sydney X Lu

    Full Text Available Allogeneic bone marrow transplantation (allo-BMT is a potentially curative therapy for a variety of hematologic diseases, but benefits, including graft-versus-tumor (GVT activity are limited by graft-versus-host-disease (GVHD. Carcinoembryonic antigen related cell adhesion molecule 1 (Ceacam1 is a transmembrane glycoprotein found on epithelium, T cells, and many tumors. It regulates a variety of physiologic and pathological processes such as tumor biology, leukocyte activation, and energy homeostasis. Previous studies suggest that Ceacam1 negatively regulates inflammation in inflammatory bowel disease models.We studied Ceacam1 as a regulator of GVHD and GVT after allogeneic bone marrow transplantation (allo-BMT in mouse models. In vivo, Ceacam1(-/- T cells caused increased GVHD mortality and GVHD of the colon, and greater numbers of donor T cells were positive for activation markers (CD25(hi, CD62L(lo. Additionally, Ceacam1(-/- CD8 T cells had greater expression of the gut-trafficking integrin α(4β(7, though both CD4 and CD8 T cells were found increased numbers in the gut post-transplant. Ceacam1(-/- recipients also experienced increased GVHD mortality and GVHD of the colon, and alloreactive T cells displayed increased activation. Additionally, Ceacam1(-/- mice had increased mortality and decreased numbers of regenerating small intestinal crypts upon radiation exposure. Conversely, Ceacam1-overexpressing T cells caused attenuated target-organ and systemic GVHD, which correlated with decreased donor T cell numbers in target tissues, and mortality. Finally, graft-versus-tumor survival in a Ceacam1(+ lymphoma model was improved in animals receiving Ceacam1(-/- vs. control T cells.We conclude that Ceacam1 regulates T cell activation, GVHD target organ damage, and numbers of donor T cells in lymphoid organs and GVHD target tissues. In recipients of allo-BMT, Ceacam1 may also regulate tissue radiosensitivity. Because of its expression on both the

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. Roles of Toll-like receptors in allogeneic islet transplantation.

    Science.gov (United States)

    Ro, Han; Hong, Juho; Kim, Beom Seok; Lee, Eun Won; Kim, Myung-Gyu; Han, Kyu Hyun; Yeom, Hye-Jung; Lee, Eun Mi; Jeong, Jong Cheol; Oh, Kook-Hwan; Ahn, Curie; Yang, Jaeseok

    2012-11-27

    Toll-like receptors (TLRs) are involved in the rejection of solid organ allografts. However, the roles of TLRs in islets are still controversial. We investigated the roles of TLRs in donor islets together with those in recipients in allogeneic islet transplantation. To assess the roles of TLRs in either donor islets or recipients, allogeneic islet transplantation was performed using myeloid differentiation factor 88 (MyD88)-knockout (KO), TLR4-KO, or Toll/interleukin-1 receptor domain-containing adaptor-inducing interferon-β (TRIF)-KO mice. Both polyriboinosinic polyribocytidylic acid and lipopolysaccharide (LPS) stimulation induced the mRNA expression of regulated and normal T cell expressed and secreted, interferon-γ-inducible protein-10, monocyte chemotactic protein-1, interleukin-8, and inducible nitric oxide synthase in murine islets, whereas the induction was attenuated in TRIF-KO, interferon-β promoter stimulator-1-KO, and TLR4-KO mice. When islets from MyD88-KO, TLR4-KO, or TRIF-KO C57BL/6 mice were transplanted to BALB/c recipients, graft survival was not better than that of wild-type (WT) islets. However, the survival of the MyD88-KO islet allograft was significantly prolonged when combined with anti-CD40L. In parallel, LPS stimulation in donor islets interfered with anti-CD40L blockade-mediated long-term survival of islet allografts in TLR4-KO recipients. LPS stimulation increased the perigraft infiltration of both T cells and macrophages. Then again, when islets from WT BALB/c mice were transplanted to MyD88-KO, TRIF-KO, or WT C57BL/6 mice, there was no difference in graft survival, although some of the MyD88-KO recipients obtained long-term graft survival. However, anti-CD40L prolonged graft survival significantly in MyD88-KO recipients. The absence of MyD88 in either donors or recipients decreased the perigraft infiltration of inflammatory cells when combined with anti-CD40L. TLRs in both donor islets and recipients are involved in islet allograft

  16. 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.

  17. 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.

  18. [Allogeneic vascularized transplantation in cases of bone and joint defects].

    Science.gov (United States)

    Hofmann, G O; Kirschner, M H; Gonschorek, O; Bühren, V

    1999-06-01

    This paper presents preliminary results of allogeneic vascularized transplantations of three femoral diaphyses and four total human knee joints. Grafts were harvested from multi-organ-donors and immediately transplanted. Osteosyntheses were performed employing intramedullary nails. Vascular pedicles of the grafts were anastomosed in end-to-side technique. Immunosuppression mainly based on Cyclosporine and Azathioprine. Grafts' perfusion was demonstrated by DSA and Duplex-sonograms, bone metabolism by SPECT-scintigraphy. Five months following transplantation osteotomies demonstrated consolidation in conventional X-rays. Biopsies of the grafted bone revealed intact osteocytes and arthroscopy demonstrated intact synovial, chondral and ligamentous structures. From the technical aspect vascularized transplantation of the femoral diaphyses and total knee joints is feasible. The main problems are of immunologic nature. Transplantations were performed respecting the ABO-compatibility but with a large HLA-mismatch. Acute and chronic rejection crises may damage the grafts. At least in synovial joints live-long immunosuppression of the recipients seems to be unavoidable.

  19. EXPERIENCE OF USING ALLOGENIC BIOIMPLANTS IN LARYNGEAL RESECTION

    Directory of Open Access Journals (Sweden)

    E. N. Novozhilova

    2017-01-01

    Full Text Available Introduction. Currently, a great importance is being attached to improvement of the surgical component of combination treatment of locally advanced laryngeal cancer. New technological capabilities (transoral microsurgery of the larynx and robotic surgery offer great opportunities for early cancer stages. However, in some cases capabilities of endoscopic laser intervention are limited. Therefore, open laryngeal resection is still relevant as it serves as the only type of radical organ preservation treatment for stages Т2–Т3. But major laryngeal resection is associated with a problem of tissue defect closure.The article describes data on the use of biocompatible materials, their advantages and disadvantages. The study objective is to present experience of using a Russian allogenic bioimplant for plastic reconstruction of the opening of the larynx after laryngeal resection.Materials and methods. The authors present their experience of using a Russian bioimplant produced in collaboration with the Samara Tissue Bank of the Research Institute of Experimental Medicine and Biotechnology of the Samara State Medical University. The material was tested in anterolateral laryngeal resection with simultaneous reconstruction in 5 patients with stages Т2–Т3 laryngeal cancer and in a patient with chondrosarcoma.Conclusion. The Russian biocompatible implant served as a reliable, simple, cheap, and effective variant of plastic material for reconstruction of the larynx.

  20. T cell reconstitution in allogeneic haematopoietic stem cell transplantation

    DEFF Research Database (Denmark)

    Kielsen, K; Jordan, K K; Uhlving, H H

    2015-01-01

    Infections and acute graft-versus-host disease (aGVHD) are major causes of treatment-related mortality and morbidity following allogeneic haematopoietic stem cell transplantation (HSCT). Both complications depend on reconstitution of the T-lymphocyte population based on donor T cells. Although...... it is well established that Interleukin-7 (IL-7) is a cytokine essential for de novo T cell development in the thymus and homoeostatic peripheral expansion of T cells, associations between circulating levels of IL-7 and T cell reconstitution following HSCT have not been investigated previously. We...... in patients treated with anti-thymocyte globulin (ATG) compared with those not treated with ATG (P = 0.0079). IL-7 levels at day +7 were negatively associated with T cell counts at day +30 to +60 (at day +60: CD3(+) : β = -10.6 × 10(6) cells/l, P = 0.0030; CD8(+) : β = -8.4 × 10(6) cells/l, P = 0.061; CD4...

  1. Pneumatosis intestinalis in children after allogeneic bone marrow transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Yeager, A M; Kanof, M E; Lake, A M; Kramer, S S; Jones, B; Saral, R; Santos, G W

    1987-01-01

    Four children, ages 3 to 8 years, developed pneumatosis intestinalis (PI) after allogeneic bone marrow transplantation (BMT) for acute leukemia or severe aplastic anemia. PI was detected at a median of 48 days (range, 10-63 days) after BMT and was associated with abdominal symptoms and clinical signs. All patients had severe systemic and/or highgrade cutaneous acute graft-versus-host disease (AGVHD) at some time after BMT and were receiving corticosteroids at the time of development of PI; however, PI was associated with concomitant severe AGVHD in only one patient. One patient with PI had Hafnia alvei bacteremia and another patient had gastroenteritis due to rotavirus and adenovirus. All patients were treated with supportive care and systemic broad-spectrum antibiotics, and PI resolved 2-16 days after onset. Two patients died with BMT-associated complications unrelated to PI. Multiple factors contribute to the development of PI after BMT, and the prognosis for recovery from PI is good with medical management alone. Overall survival in these patients is dependent on the frequency and severity of other conditions, such as AGVHD and opportunistic infections, after BMT.

  2. Allogenic banking of dental pulp stem cells for innovative therapeutics.

    Science.gov (United States)

    Collart-Dutilleul, Pierre-Yves; Chaubron, Franck; De Vos, John; Cuisinier, Frédéric J

    2015-08-26

    Medical research in regenerative medicine and cell-based therapy has brought encouraging perspectives for the use of stem cells in clinical trials. Multiple types of stem cells, from progenitors to pluripotent stem cells, have been investigated. Among these, dental pulp stem cells (DPSCs) are mesenchymal multipotent cells coming from the dental pulp, which is the soft tissue within teeth. They represent an interesting adult stem cell source because they are recovered in large amount in dental pulps with non-invasive techniques compared to other adult stem cell sources. DPSCs can be obtained from discarded teeth, especially wisdom teeth extracted for orthodontic reasons. To shift from promising preclinical results to therapeutic applications to human, DPSCs must be prepared in clinical grade lots and transformed into advanced therapy medicinal products (ATMP). As the production of patient-specific stem cells is costly and time-consuming, allogenic biobanking of clinical grade human leukocyte antigen (HLA)-typed DPSC lines provides efficient innovative therapeutic products. DPSC biobanks represent industrial and therapeutic innovations by using discarded biological tissues (dental pulps) as a source of mesenchymal stem cells to produce and store, in good manufacturing practice (GMP) conditions, DPSC therapeutic batches. In this review, we discuss about the challenges to transfer biological samples from a donor to HLA-typed DPSC therapeutic lots, following regulations, GMP guidelines and ethical principles. We also present some clinical applications, for which there is no efficient therapeutics so far, but that DPSCs-based ATMP could potentially treat.

  3. Pneumatosis intestinalis in children after allogeneic bone marrow transplantation

    International Nuclear Information System (INIS)

    Yeager, A.M.; Kanof, M.E.; Lake, A.M.; Kramer, S.S.; Jones, B.; Saral, R.; Santos, G.W.

    1987-01-01

    Four children, ages 3 to 8 years, developed pneumatosis intestinalis (PI) after allogeneic bone marrow transplantation (BMT) for acute leukemia or severe aplastic anemia. PI was detected at a median of 48 days (range, 10-63 days) after BMT and was associated with abdominal symptoms and clinical signs. All patients had severe systemic and/or highgrade cutaneous acute graft-versus-host disease (AGVHD) at some time after BMT and were receiving corticosteroids at the time of development of PI; however, PI was associated with concomitant severe AGVHD in only one patient. One patient with PI had Hafnia alvei bacteremia and another patient had gastroenteritis due to rotavirus and adenovirus. All patients were treated with supportive care and systemic broad-spectrum antibiotics, and PI resolved 2-16 days after onset. Two patients died with BMT-associated complications unrelated to PI. Multiple factors contribute to the development of PI after BMT, and the prognosis for recovery from PI is good with medical management alone. Overall survival in these patients is dependent on the frequency and severity of other conditions, such as AGVHD and opportunistic infections, after BMT. (orig.)

  4. Interspecies chimera between primate embryonic stem cells and mouse embryos: monkey ESCs engraft into mouse embryos, but not post-implantation fetuses.

    Science.gov (United States)

    Simerly, Calvin; McFarland, Dave; Castro, Carlos; Lin, Chih-Cheng; Redinger, Carrie; Jacoby, Ethan; Mich-Basso, Jocelyn; Orwig, Kyle; Mills, Parker; Ahrens, Eric; Navara, Chris; Schatten, Gerald

    2011-07-01

    Unequivocal evidence for pluripotency in which embryonic stem cells contribute to chimeric offspring has yet to be demonstrated in human or nonhuman primates (NHPs). Here, rhesus and baboons ESCs were investigated in interspecific mouse chimera generated by aggregation or blastocyst injection. Aggregation chimera produced mouse blastocysts with GFP-nhpESCs at the inner cell mass (ICM), and embryo transfers (ETs) generated dimly-fluorescencing abnormal fetuses. Direct injection of GFP-nhpESCs into blastocysts produced normal non-GFP-fluorescencing fetuses. Injected chimera showed >70% loss of GFP-nhpESCs after 21 h culture. Outgrowths of all chimeric blastocysts established distinct but separate mouse- and NHP-ESC colonies. Extensive endogenous autofluorescence compromised anti-GFP detection and PCR analysis did not detect nhpESCs in fetuses. NhpESCs localize to the ICM in chimera and generate pregnancies. Because primate ESCs do not engraft post-implantation, and also because endogenous autofluorescence results in misleading positive signals, interspecific chimera assays for pluripotency with primate stem cells is unreliable with the currently available ESCs. Testing primate ESCs reprogrammed into even more naïve states in these inter-specific chimera assays will be an important future endeavor. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. A standardized multidisciplinary approach reduces the use of allogeneic blood products in patients undergoing cardiac surgery.

    Science.gov (United States)

    Van der Linden, P; De Hert, S; Daper, A; Trenchant, A; Jacobs, D; De Boelpaepe, C; Kimbimbi, P; Defrance, P; Simoens, G

    2001-10-01

    Individual and institutional practices remain an independent predictor factor for allogeneic blood transfusion. Application of a standardized multidisciplinary transfusion strategy should reduce the use of allogeneic blood transfusion in major surgical patients. This prospective non randomized observational study evaluated the effects of a standardized multidisciplinary transfusion strategy on allogeneic blood products exposure in patients undergoing non-emergent cardiac surgery. The developed strategy involved a standardized blood conservation program and a multidisciplinary allogeneic blood transfusion policy based mainly on clinical judgement, not only on a specific hemoglobin concentration. Data obtained in a first group including patients operated from September 1997 to August 1998 (Group pre: n=321), when the transfusion strategy was progressively developed, were compared to those obtained in a second group, including patients operated from September 1998 to August 1999 (Group post: n=315) when the transfusion strategy was applied uniformly. Patient populations and surgical procedures were similar. Patients in Group post underwent acute normovolemic hemodilution more frequently, had a higher core temperature at arrival in the intensive care unit and presented lower postoperative blood losses at day one. Three hundred forty units of packed red blood cells were transfused in 33% of the patients in Group pre whereas 161 units were transfused in 18% of the patients in Group post (P <0.001). Pre- and postoperative hemoglobin concentrations, mortality and morbidity were not different among groups. Development of a standardized multidisciplinary transfusion strategy markedly reduced the exposure of cardiac surgery patients to allogeneic blood.

  6. New type of chimera structures in a ring of bistable FitzHugh–Nagumo oscillators with nonlocal interaction

    Energy Technology Data Exchange (ETDEWEB)

    Shepelev, I.A., E-mail: igor_sar@li.ru; Vadivasova, T.E., E-mail: vadivasovate@yandex.ru; Bukh, A.V., E-mail: buh.andrey@yandex.ru; Strelkova, G.I., E-mail: strelkovagi@info.sgu.ru; Anishchenko, V.S., E-mail: wadim@info.sgu.ru

    2017-04-25

    We study the spatiotemporal dynamics of a ring of nonlocally coupled FitzHugh–Nagumo oscillators in the bistable regime. A new type of chimera patterns has been found in the noise-free network and when isolated elements do not oscillate. The region of existence of these structures has been explored when the coupling range and the coupling strength between the network elements are varied. - Highlights: • Dynamics of a ring of nonlocally coupled FitzHugh–Nagumo oscillators in the bistable regime is studied. • A new type of chimera patterns has been found in the noise-free network. • The region of existence of new structures has been explored when varying the coupling parameters.

  7. New type of chimera structures in a ring of bistable FitzHugh-Nagumo oscillators with nonlocal interaction

    Science.gov (United States)

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

    2017-04-01

    We study the spatiotemporal dynamics of a ring of nonlocally coupled FitzHugh-Nagumo oscillators in the bistable regime. A new type of chimera patterns has been found in the noise-free network and when isolated elements do not oscillate. The region of existence of these structures has been explored when the coupling range and the coupling strength between the network elements are varied.

  8. Analysis of the results of allogeneic hematopoietic stem cell transplantation depending on HLA matching of the unrelated donor / recipient pair

    Directory of Open Access Journals (Sweden)

    Ye. V. Kuzmich

    2015-01-01

    Full Text Available HLA matching of the donor / recipient pair is a major factor associated with the outcome of allogeneic stem cell transplantation. In the presentstudy we analyzed the risk of severe acute graft-versus-host disease, graft failure, 2.year overall survival of the patients after allogeneic stem cell transplantation depending on HLA matching of the unrelated donor / recipient pair.

  9. Long-term outcomes among older patients following nonmyeloablative conditioning and allogeneic hematopoietic cell transplantation for advanced hematologic malignancies

    DEFF Research Database (Denmark)

    Sorror, Mohamed L; Sandmaier, Brenda M; Storer, Barry E

    2011-01-01

    A minimally toxic nonmyeloablative regimen was developed for allogeneic hematopoietic cell transplantation (HCT) to treat patients with advanced hematologic malignancies who are older or have comorbid conditions.......A minimally toxic nonmyeloablative regimen was developed for allogeneic hematopoietic cell transplantation (HCT) to treat patients with advanced hematologic malignancies who are older or have comorbid conditions....

  10. DAS181 Treatment of Severe Parainfluenza Virus 3 Pneumonia in Allogeneic Hematopoietic Stem Cell Transplant Recipients Requiring Mechanical Ventilation

    Directory of Open Access Journals (Sweden)

    B. Dhakal

    2016-01-01

    Full Text Available Parainfluenza virus (PIV may cause life-threatening pneumonia in allogeneic hematopoietic stem cell transplant (HSCT recipients. Currently, there are no proven effective therapies. We report the use of inhaled DAS181, a novel sialidase fusion protein, for treatment of PIV type 3 pneumonia in two allogeneic hematopoietic SCT recipients with respiratory failure.

  11. Programmable display of DNA-protein chimeras for controlling cell-hydrogel interactions via reversible intermolecular hybridization.

    Science.gov (United States)

    Zhang, Zhaoyang; Li, Shihui; Chen, Niancao; Yang, Cheng; Wang, Yong

    2013-04-08

    Extensive studies have been recently carried out to achieve dynamic control of cell-material interactions primarily through physicochemical stimulation. The purpose of this study was to apply reversible intermolecular hybridization to program cell-hydrogel interactions in physiological conditions based on DNA-antibody chimeras and complementary oligonucleotides. The results showed that DNA oligonucleotides could be captured to and released from the immobilizing DNA-functionalized hydrogels with high specificity via DNA hybridization. Accordingly, DNA-antibody chimeras were captured to the hydrogels, successfully inducing specific cell attachment. The cell attachment to the hydrogels reached the plateau at approximately half an hour after the functionalized hydrogels and the cells were incubated together. The attached cells were rapidly released from the bound hydrogels when triggering complementary oligonucleotides were introduced to the system. However, the capability of the triggering complementary oligonucleotides in releasing cells was affected by the length of intermolecular hybridization. The length needed to be at least more than 20 base pairs in the current experimental setting. Notably, because the procedure of intermolecular hybridization did not involve any harsh condition, the released cells maintained the same viability as that of the cultured cells. The functionalized hydrogels also exhibited the potential to catch and release cells repeatedly. Therefore, this study demonstrates that it is promising to regulate cell-material interactions dynamically through the DNA-programmed display of DNA-protein chimeras.

  12. The ethics of killing human/great-ape chimeras for their organs: a reply to Shaw et al.

    Science.gov (United States)

    Palacios-González, César

    2016-06-01

    The aim of this paper is to critically examine David Shaw, Wybo Dondorp, and Guido de Wert's arguments in favour of the procurement of human organs from human/nonhuman-primate chimeras, specifically from great-ape/human chimeras. My main claim is that their arguments fail and are in need of substantial revision. To prove this I first introduce the topic, and then reconstruct Shaw et al.'s position and arguments. Next, I show that Shaw et al.: (1) failed to properly apply the subsidiarity and proportionality principles; (2) neglected species overlapping cases in their ethical assessment; (3) ignored the ethics literature on borderline persons; and (4) misunderstood McMahan's two-tiered moral theory. These mistakes render an important part of their conclusions either false or problematic to the point that they would no longer endorse them. Finally I will briefly mention a possible multipolar solution to the human organ shortage problem that would reduce the need for chimeras' organs.

  13. Allogenic sedimentary components of Bear Lake, Utah and Idaho

    Science.gov (United States)

    Rosenbaum, J.G.; Dean, W.E.; Reynolds, R.L.; Reheis, M.C.

    2009-01-01

    Bear Lake is a long-lived lake filling a tectonic depression between the Bear River Range to the west and the Bear River Plateau to the east, and straddling the border between Utah and Idaho. Mineralogy, elemental geochemistry, and magnetic properties provide information about variations in provenance of allogenic lithic material in last-glacial-age, quartz-rich sediment in Bear Lake. Grain-size data from the siliciclastic fraction of late-glacial to Holocene carbonate-rich sediments provide information about variations in lake level. For the quartz-rich lower unit, which was deposited while the Bear River fl owed into and out of the lake, four source areas are recognized on the basis of modern fluvial samples with contrasting properties that reflect differences in bedrock geology and in magnetite content from dust. One of these areas is underlain by hematite-rich Uinta Mountain Group rocks in the headwaters of the Bear River. Although Uinta Mountain Group rocks make up a small fraction of the catchment, hematite-rich material from this area is an important component of the lower unit. This material is interpreted to be glacial fl our. Variations in the input of glacial flour are interpreted as having caused quasi-cyclical variations in mineralogical and elemental concentrations, and in magnetic properties within the lower unit. The carbonate-rich younger unit was deposited under conditions similar to those of the modern lake, with the Bear River largely bypassing the lake. For two cores taken in more than 30 m of water, median grain sizes in this unit range from ???6 ??m to more than 30 ??m, with the coarsest grain sizes associated with beach or shallow-water deposits. Similar grain-size variations are observed as a function of water depth in the modern lake and provide the basis for interpreting the core grain-size data in terms of lake level. Copyright ?? 2009 The Geological Society of America.

  14. Intravenous Tranexamic Acid Decreases Allogeneic Transfusion Requirements in Periacetabular Osteotomy.

    Science.gov (United States)

    Bryan, Andrew J; Sanders, Thomas L; Trousdale, Robert T; Sierra, Rafael J

    2016-01-01

    Bernese (Ganz) periacetabular osteotomy is associated with significant blood loss and the need for perioperative transfusion. Tranexamic acid decreases blood loss and minimizes transfusion rates in total joint arthroplasty. However, no reports have described its use in patients undergoing Bernese periacetabular osteotomy. This study reports the use of intravenous tranexamic acid in these patients. The study included 137 patients (150 hips) who underwent isolated periacetabular osteotomy at a single institution between 2003 and 2014. Of these, 68 patients (75 hips) received intravenous tranexamic acid 1 g at the time of incision and 1 g at the time of closure. A group of 69 patients (75 hips) served as control subjects who underwent periacetabular osteotomy without administration of intravenous tranexamic acid. Thromboembolic disease was defined as deep venous thrombosis or pulmonary embolism occurring within 6 weeks of surgery. Outcomes measured included transfusion requirements, pre- and postoperative hemoglobin values, operative times, and thromboembolic disease rates. Aspirin was used as the thromboembolic prophylactic regimen in 95% of patients. The rate of allogeneic transfusion was 0 in the tranexamic acid group compared with 21% in the control group (P=.0001). No significant difference was found in the autologous cell salvage requirement (.96 vs 1.01; P=.43) or the thromboembolic disease rate between the tranexamic acid group and the control group (2.67% vs 1.33%; P=.31). The use of intravenous tranexamic acid led to a decreased transfusion requirement with no increased risk of thromboembolic disease in this contemporary cohort of patients undergoing periacetabular osteotomy. Copyright 2016, SLACK Incorporated.

  15. A protocol avoiding allogeneic transfusion in joint arthroplasties.

    Science.gov (United States)

    Suh, You-Sung; Nho, Jae-Hwi; Choi, Hyung-Suk; Ha, Yong-Chan; Park, Jong-Seok; Koo, Kyung-Hoi

    2016-09-01

    Arthroplasties of hip and knee are associated with blood loss, which may lead to adverse patient outcome. Performing arthroplasties in Jehovah's Witness patients who do not accept transfusion has been a matter of concern. We developed a protocol, which avoids transfusion in arthroplasties of Jehovah's Witness patients, and evaluated the feasibility and safety of the protocol. The target of preoperative hemoglobin was more than 10 g/dL. When preoperative hemoglobin was lower than 10 g/dL, 4000 U erythropoietin (3 times a week) and 100 mg iron supplement (every day) were administered until the hemoglobin reached 10 g/dL. When the preoperative hemoglobin was higher than 10 g/dL, 4000 U erythropoietin and 100 mg iron supplement were administered once, before operation. During the operation, cell saver was used. Postoperatively, erythropoietin and iron supplements were administered until the hemoglobin reached 10 g/dL, similar to the preoperative protocol. We evaluated the feasibility of our protocol, perioperative complications and hematologic changes. From 2002 to 2014, 186 Witness patients visited our department. In 179 patients (96.2 %), 77 total knee arthroplasties, 69 bipolar hemiarthroplasties and 33 total hip arthroplasties were performed. The mean hemoglobin level was 12.3 g/dL preoperatively, 9.4 g/dL on postoperative day 3 and 10.3 g/dL on postoperative day 7. One patient died immediately after the arthroplasty and the remaining 178 patients survived. Total joint arthroplasty could be done without transfusion using this protocol in most of our patients. The rates of infection and mortality were similar with known infection and mortality rates of arthroplasties. In patients who do not want allogeneic transfusions, our protocol is a safe alternative to perform joint arthroplasties.

  16. Sclerodermatous GVHD after Allogeneic Bone Marrow Transplant: a Review

    Directory of Open Access Journals (Sweden)

    Gagan Raju

    2017-05-01

    Full Text Available Chronic graft versus host disease (cGVHD is the leading cause of non-relapse mortality after allogeneic hematopoietic bone marrow transplantation (HCT for blood malignancy in patients who survive for more than two years. cGVHD can significantly affect quality of life and cause decreased mobility amongst other grave consequences such as end-organ damage, contributing to morbidity and mortality rates for recipients of HCT. Unlike acute GVHD (aGVHD, the chronic variant of graft versus host disease (GVHD has complex immunopathology involving both humoral and cell immunity. It typically affects the integumentary system, though is known to also affect myofascial, mucocutaneous tissues as well as cause end organ damage ultimately resulting in death. Sclerodermatous cGVHD is a type of cGVHD characterized by involvement of the skin, subcutaneous tissue and fascia without evidence of disease in the viscera. Manifestations of this disease are often evocative of autoimmune disease, which is a self-directed inflammatory reaction to the innate and adaptive immune system in various tissues or multiple organ systems. This inflammatory reaction gives rise to autoantibodies as well as B-cell and T-cell mediated direct toxicity which can cause chronic inflammatory changes of tissues ultimately resulting in tissue scarring and end organ dysfunction. We aim to review the literature on this grave disease and elucidate aspects of the immunopathology of chronic sclerodermatous GVHD in hopes that it may lead to revelations inspiring novel therapies after its diagnosis or preventative measures before stem cell transplantation for malignancy.

  17. Allogeneic stem cell transplantation for thalassemia major in India

    Directory of Open Access Journals (Sweden)

    Vikram Mathews

    2017-12-01

    Full Text Available Allogeneic stem cell transplantation (allo-SCT is the only currently available curative treatment for thalassemia major. Since it was first done in 1981, several thousand patients have benefited from it and it is now possible to offer this treatment in different parts of the world with good results. With better risk stratification and supportive care, the results of allo-SCT are now very good even in high risk patients who have significant iron overload related organ dysfunction. The improvements have mainly been in the conditioning strategies with less toxic myeloablation and management of the complications of SCT. However, several challenges remain. Transplant related complications still cause significant morbidity and mortality. There is data to show that the results of transplantation as best if done in well transfused and chelated patients <7 years of age. As only a third of the patients will have a matched related donor, there is need for investigating SCT with alternative donors. Experience with SCT for thalassemia major from matched unrelated donors or haplo-identical donors is still limited but needs further exploration. Adequate management needs to be provided post-SCT for all pre-existing complications particularly iron chelation to prevent further organ dysfunction. Systematic follow-up is needed to measure long term outcomes. The biggest challenges in India are the cost of this treatment and access to centres capable of providing this treatment. With greater support from the government, health insurance and philanthropic programs, there has been a rapid increase in the number of SCTs for thalassemia major in India. The number centres providing this treatment are also increasing making this curative treatment more widely available in India.

  18. Mesenchymal Stem Cells Enhance Allogeneic Islet Engraftment in Nonhuman Primates

    Science.gov (United States)

    Berman, Dora M.; Willman, Melissa A.; Han, Dongmei; Kleiner, Gary; Kenyon, Norman M.; Cabrera, Over; Karl, Julie A.; Wiseman, Roger W.; O'Connor, David H.; Bartholomew, Amelia M.; Kenyon, Norma S.

    2010-01-01

    OBJECTIVE To test the graft-promoting effects of mesenchymal stem cells (MSCs) in a cynomolgus monkey model of islet/bone marrow transplantation. RESEARCH DESIGN AND METHODS Cynomolgus MSCs were obtained from iliac crest aspirate and characterized through passage 11 for phenotype, gene expression, differentiation potential, and karyotype. Allogeneic donor MSCs were cotransplanted intraportally with islets on postoperative day (POD) 0 and intravenously with donor marrow on PODs 5 and 11. Recipients were followed for stabilization of blood glucose levels, reduction of exogenous insulin requirement (EIR), C-peptide levels, changes in peripheral blood T regulatory cells, and chimerism. Destabilization of glycemia and increases in EIR were used as signs of rejection; additional intravenous MSCs were administered to test the effect on reversal of rejection. RESULTS MSC phenotype and a normal karyotype were observed through passage 11. IL-6, IL-10, vascular endothelial growth factor, TGF-β, hepatocyte growth factor, and galectin-1 gene expression levels varied among donors. MSC treatment significantly enhanced islet engraftment and function at 1 month posttransplant (n = 8), as compared with animals that received islets without MSCs (n = 3). Additional infusions of donor or third-party MSCs resulted in reversal of rejection episodes and prolongation of islet function in two animals. Stable islet allograft function was associated with increased numbers of regulatory T-cells in peripheral blood. CONCLUSIONS MSCs may provide an important approach for enhancement of islet engraftment, thereby decreasing the numbers of islets needed to achieve insulin independence. Furthermore, MSCs may serve as a new, safe, and effective antirejection therapy. PMID:20622174

  19. Modulation of allogeneic stimulation in man. I. Characterization of an in vitro induced suppressor macrophage population

    International Nuclear Information System (INIS)

    Stux, S.V.; Dubey, D.P.; Yunis, E.J.

    1981-01-01

    Cultured human peripheral blood mononuclear cells suppressed the allogeneic response of fresh autologous lymphocytes. This suppressor activity developed gradually over a period of one week. The cells primarily responsible for this effect were enriched by Ficoll density gradient centrifugation. It was found that the suppressor cell is a large, low density nylon wool adherent, radioresistant, phagocytic, and nonspecific esterase positive mononuclear cell. Moreover, these cells did not form E rosettes and were Fc positive. Electron microscopy confirmed that suppressor cells were macrophage like. Suppressor activity was not due to cytotoxicity, crowding, or steric hinderance by the cultured cells. The suppressor macrophage population did not appear to inhibit the allogeneic response via prostaglandin or arginase release, or interfere with the tritiated thymidine uptake by release of endogenous thymidine. The above system is viewed as an in vitro model of immune regulation by suppressor macrophages, in the context of allogeneic response

  20. Allogenic bone grafts used at Central Hospital during June 1995 to July 1998

    International Nuclear Information System (INIS)

    Yolchai Jongjirasiri; Yongyudh Vajaradul

    1999-01-01

    Producing and using allogenic bone graft in Thailand began ten years ago. There are approximately 1,000 cases a year on orthopaedic surgery at Central Hospital. For using allogenic bone graft from the Bangkok Biomaterial Center, 66 cases were operated since June 1995. This was generated by 30 in males, 36 in females and by ages between 12-81 years old. After the operation, 43 cases had bone gap from injuries and 19 cases, fusion of spondylolisthesis and scoliosis were done. Four cases had tumor surgery, and 59 out of 66 cases had good bone union that is 89%. Delayed union happened in 6 cases only. Immune response to allogenic bone graft has not been found yet

  1. Alternative procedures for reducing allogeneic blood transfusion in elective orthopedic surgery.

    Science.gov (United States)

    Kleinert, Kathrin; Theusinger, Oliver M; Nuernberg, Johannes; Werner, Clément M L

    2010-09-01

    Perioperative blood loss is a major problem in elective orthopedic surgery. Allogeneic transfusion is the standard treatment for perioperative blood loss resulting in low postoperative hemoglobin, but it has a number of well-recognized risks, complications, and costs. Alternatives to allogeneic blood transfusion include preoperative autologous donation and intraoperative salvage with postoperative autotransfusion. Orthopedic surgeons are often unaware of the different pre- and intraoperative possibilities of reducing blood loss and leave the management of coagulation and use of blood products completely to the anesthesiologists. The goal of this review is to compare alternatives to allogeneic blood transfusion from an orthopedic and anesthesia point of view focusing on estimated costs and acceptance by both parties.

  2. A Navier-Strokes Chimera Code on the Connection Machine CM-5: Design and Performance

    Science.gov (United States)

    Jespersen, Dennis C.; Levit, Creon; Kwak, Dochan (Technical Monitor)

    1994-01-01

    We have implemented a three-dimensional compressible Navier-Stokes code on the Connection Machine CM-5. The code is set up for implicit time-stepping on single or multiple structured grids. For multiple grids and geometrically complex problems, we follow the 'chimera' approach, where flow data on one zone is interpolated onto another in the region of overlap. We will describe our design philosophy and give some timing results for the current code. A parallel machine like the CM-5 is well-suited for finite-difference methods on structured grids. The regular pattern of connections of a structured mesh maps well onto the architecture of the machine. So the first design choice, finite differences on a structured mesh, is natural. We use centered differences in space, with added artificial dissipation terms. When numerically solving the Navier-Stokes equations, there are liable to be some mesh cells near a solid body that are small in at least one direction. This mesh cell geometry can impose a very severe CFL (Courant-Friedrichs-Lewy) condition on the time step for explicit time-stepping methods. Thus, though explicit time-stepping is well-suited to the architecture of the machine, we have adopted implicit time-stepping. We have further taken the approximate factorization approach. This creates the need to solve large banded linear systems and creates the first possible barrier to an efficient algorithm. To overcome this first possible barrier we have considered two options. The first is just to solve the banded linear systems with data spread over the whole machine, using whatever fast method is available. This option is adequate for solving scalar tridiagonal systems, but for scalar pentadiagonal or block tridiagonal systems it is somewhat slower than desired. The second option is to 'transpose' the flow and geometry variables as part of the time-stepping process: Start with x-lines of data in-processor. Form explicit terms in x, then transpose so y-lines of data are

  3. Allogeneic human dermal fibroblasts are viable in peripheral blood mononuclear co-culture

    Directory of Open Access Journals (Sweden)

    Restu Syamsul Hadi

    2014-08-01

    Full Text Available Background Transplanted allogeneic dermal fibroblasts retain stem cell subpopulations, and are easily isolated, expanded and stored using standard techniques. Their potential for regenerative therapy of chronic wounds should be evaluated. The aim of this study was to determine allogeneic fibroblast viability in the presence of peripheral blood mononuclear cells (PBMC. Methods In this experimental study, fibroblasts were isolated from foreskin explants, expanded in the presence of serum, and stored using slow-freezing. We used one intervention group of allogeneic fibroblasts co-cultured with PBMC and 2 control groups of separate fibroblast and PBMC cultures.Fibroblasts were characterized by their collagen secretion and octamer-binding transcription factor 4 (OCT4 expression. Viability was evaluated using water soluble tetrazolium-1 (WST-1 proliferation assay. Absorbances were measured at 450 nm. Data analysis was performed by student’s paired t-test. Results Dermal fibroblasts were shown to secrete collagen, express OCT4, be recoverable after cryopreservation, and become attached to the culture dish in a co-culture with PBMC. Co-cultured and control fibroblasts had no significantly different cell viabilities (p>0.05. Calculated viable cell numbers increased 1.8 and 5.1-fold, respectively, at days 2 and 4 in vitro. Both groups showed comparable doubling times at days 2 and 4 in vitro. PBMC did not interfere with allogeneic fibroblast viability and proliferative capacity Conclusions Allogeneic fibroblasts remain viable and proliferate in the presence of host PBMC. Future research should evaluate allogeneic human dermal fibroblast competency in clinical settings. Dermal fibroblasts are a potential source for cell therapy in chronic wound management.

  4. Allogeneic stem cell transplantation for patients harboring T315I BCR-ABL mutated leukemias

    DEFF Research Database (Denmark)

    Nicolini, Franck Emmanuel; Basak, Grzegorz W; Soverini, Simona

    2011-01-01

    T315I(+) Philadelphia chromosome-positive leukemias are inherently resistant to all licensed tyrosine kinase inhibitors, and therapeutic options remain limited. We report the outcome of allogeneic stem cell transplantation in 64 patients with documented BCR-ABL(T315I) mutations. Median follow......) as unfavorable factors. We conclude that allogeneic stem cell transplantation represents a valuable therapeutic tool for eligible patients with BCR-ABL(T315I) mutation, a tool that may or may not be replaced by third-generation tyrosine kinase inhibitors....

  5. Immune competence in /sup 90/Sr-exposed, adult thymectomized and antilymphocyteglobulin-treated CBA mice. Pt. 1. Allogenic skin graft reaction

    Energy Technology Data Exchange (ETDEWEB)

    Bierke, P.

    1989-01-01

    CBA mice subjected to either adult thymectomy, internal exposure to /sup 90/Sr or antilymphocyteglobulin treatment separately, or to combinations of the three were tested for cellular immune competence using their reaction to allogenic skin grafts. Peripheral blood white cell counts did not reveal any obvious correlation between the degree of mononuclear cell depletion and the ability to accept grafts, suggesting that the particular treatments depleted specific fractions of mononuclear cells, differing in their extent of involvement in the rejection process. No single treatment alone induced a significant prolongation in the time elapsed before graft rejection. Adult thymectomy followed by appropriate antilymphocyteglobulin treatment induced severe lymphocytopenia and a profound suppression of the cell-mediate immune system, as evidenced by the acceptance of allogenic skin grafts. When applied to /sup 90/Sr-preexposed mice the same treatment induced lifelong acceptance of grafts, indicating a similar, though weaker immunosuppressive impact of /sup 90/Sr. Hence it was possible to significantly enhance immunosuppression in /sup 90/Sr-exposed mice. This in vivo model should be useful when investigating the role of immunological responsiveness in radiation carcinogenesis. (orig.).

  6. Autoreactive T cell clones specific for class I and class II HLA antigens isolated from a human chimera

    NARCIS (Netherlands)

    Roncarolo, M. G.; Yssel, H.; Touraine, J. L.; Betuel, H.; de Vries, J. E.; Spits, H.

    1988-01-01

    T cell clones of donor origin that specifically react with recipient cells were obtained from a SCID patient successfully reconstituted by allogeneic fetal liver and thymus transplantation performed 10 yr ago. The majority of these clones displayed both cytotoxic and proliferative responses towards

  7. 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.

  8. STAT3 Gene Silencing by Aptamer-siRNA Chimera as Selective Therapeutic for Glioblastoma

    Directory of Open Access Journals (Sweden)

    Carla Lucia Esposito

    2018-03-01

    Full Text Available Glioblastoma (GBM is the most frequent and aggressive primary brain tumor in adults, and despite advances in neuro-oncology, the prognosis for patients remains dismal. The signal transducer and activator of transcription-3 (STAT3 has been reported as a key regulator of the highly aggressive mesenchymal GBM subtype, and its direct silencing (by RNAi oligonucleotides has revealed a great potential as an anti-cancer therapy. However, clinical use of oligonucleotide-based therapies is dependent on safer ways for tissue-specific targeting and increased membrane penetration. The objective of this study is to explore the use of nucleic acid aptamers as carriers to specifically drive a STAT3 siRNA to GBM cells in a receptor-dependent manner. Using an aptamer that binds to and antagonizes the oncogenic receptor tyrosine kinase PDGFRβ (Gint4.T, here we describe the design of a novel aptamer-siRNA chimera (Gint4.T-STAT3 to target STAT3. We demonstrate the efficient delivery and silencing of STAT3 in PDGFRβ+ GBM cells. Importantly, the conjugate reduces cell viability and migration in vitro and inhibits tumor growth and angiogenesis in vivo in a subcutaneous xenograft mouse model. Our data reveals Gint4.T-STAT3 conjugate as a novel molecule with great translational potential for GBM therapy.

  9. Anti-inflammatory, antiproliferative, and cytoprotective activity of NO chimera nitrates of use in cancer chemoprevention.

    Science.gov (United States)

    Hagos, Ghenet K; Abdul-Hay, Samer O; Sohn, Johann; Edirisinghe, Praneeth D; Chandrasena, R Esala P; Wang, Zhiqiang; Li, Qian; Thatcher, Gregory R J

    2008-11-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) have shown promise in colorectal cancer (CRC), but they are compromised by gastrotoxicity. NO-NSAIDs are hybrid nitrates conjugated to an NSAID designed to exploit the gastroprotective properties of NO bioactivity. The NO chimera ethyl 2-((2,3-bis(nitrooxy)propyl)disulfanyl)benzoate (GT-094), a novel nitrate containing an NSAID and disulfide pharmacophores, is effective in vivo in rat models of CRC and is a lead compound for design of agents of use in CRC. Preferred chemopreventive agents possess 1) antiproliferative and 2) anti-inflammatory actions and 3) the ability to induce cytoprotective phase 2 enzymes. To determine the contribution of each pharmacophore to the biological activity of GT-094, these three biological activities were studied in vitro in compounds that deconstructed the structural elements of the lead GT-094. The anti-inflammatory and antiproliferative actions of GT-094 in vivo were recapitulated in vitro, and GT-094 was seen to induce phase 2 enzymes via the antioxidant responsive element. In the variety of colon, macrophage-like, and liver cell lines studied, the evidence from structure-activity relationships was that the disulfide structural element of GT-094 is the dominant contributor in vitro to the anti-inflammatory activity, antiproliferation, and enzyme induction. The results provide a direction for lead compound refinement. The evidence for a contribution from the NO mimetic activity of nitrates in vitro was equivocal, and combinations of nitrates with acetylsalicylic acid were inactive.

  10. Aerodynamic study of sounding rocket flows using Chimera and patched multiblock meshes

    Directory of Open Access Journals (Sweden)

    João Alves de Oliveira Neto

    2011-01-01

    Full Text Available Aerodynamic flow simulations over a typical sounding rocket are presented in this paper. The work is inserted in the effort of developing computational tools necessary to simulate aerodynamic flows over configurations of interest for Instituto de Aeronáutica e Espaço of Departamento de Ciência e Tecnologia Aeroespacial. Sounding rocket configurations usually require fairly large fins and, quite frequently, have more than one set of fins. In order to be able to handle such configurations, the present paper presents a novel methodology which combines both Chimera and patched multiblock grids in the discretization of the computational domain. The flows of interest are modeled using the 3-D Euler equations and the work describes the details of discretization procedure, which uses a finite difference approach for structure, body-conforming, multiblock grids. The method is used to calculate the aerodynamics of a sounding rocket vehicle. The results indicate that the present approach can be a powerful aerodynamic analysis and design tool.

  11. Fragmentation studies with the CHIMERA detector at LNS in Catania: recent progress

    Energy Technology Data Exchange (ETDEWEB)

    Pagano, A.; Alderighi, M.; Amorini, F.; Anzalone, A.; Arena, L.; Auditore, L.; Baran, V.; Bartolucci, M.; Berceanu, I.; Blicharska, J.; Brzychczyk, J.; Bonasera, A.; Borderie, B.; Bougault, R.; Bruno, M.; Cardella, G.; Cavallaro, S.; Chatterjee, M.B.; Chbihi, A.; Cibor, J.; Colonna, M.; D' Agostino, M.; Dayras, R.; De Filippo, E.; Di Toro, M.; Gawlikowicz, W.; Geraci, E.; Giustolisi, F.; Grzeszczuk, A.; Guazzoni, P.; Guinet, D.; Iacono-Manno, M.; Kowalski, S.; La Guidara, E.; Lanzano, G.; Lanzalone, G.; Le Neindre, N.; Li, S.; Lo Nigro, S.; Maiolino, C.; Majka, Z.; Manfredi, G.; Paduszynski, T.; Papa, M.; Petrovici, M.; Piasecki, E.; Pirrone, S.; Planeta, R.; Politi, G.; Pop, A.; Porto, F.; Rivet, M.F.; Rosato, E.; Rizzo, F.; Russo, S.; Russotto, P.; Sassi, M.; Sechi, G.; Simion, V.; Siwek-Wilczynska, K.; Skwira, I.; Sperduto, M.L.; Steckmeyer, J.C.; Swiderski, L.; Trifiro, A.; Trimarchi, M.; Vannini, G.; Vigilante, M.; Wieleczko, J.P.; Wilczynski, J.; Wu, H.; Xiao, Z.; Zetta, L.; Zipper, W

    2004-04-05

    The new detector CHIMERA, in its final 4{pi} configuration, has been installed at Laboratori Nazionali del Sud (LNS) in Catania in January 2003. Beams of different energies ranging from protons to Au ions were delivered by the Tandem and the Super Conducting Cyclotron for nuclear reaction studies, in agreement with the approval of the Scientific Advisory Committee of LNS. Recent experimental results confirm very low energy thresholds of the trigger (below 0.5 MeV/nucleon), ensured within a wide dynamical range. Good characteristics of identification of light charged particles and heavy fragments have been obtained by using three detection techniques: {delta}E-E, {delta}E-time of flight, and the Pulse-Shape discrimination method. We present results of recent analysis concerning the production of intermediate mass fragments (IMF) in semi-peripheral collisions. Our results combined with theoretical Boltzmann-Nordheim-Vlasov simulations clearly demonstrate the presence of very fast processes of IMF production in the overlapping region of the target and projectile nuclei during re-separation, i.e. in the time scale comparable with the collision time. Evidence for slower, sequential-like production of IMF's is also shown.

  12. Chimeras in leaky integrate-and-fire neural networks: effects of reflecting connectivities

    Science.gov (United States)

    Tsigkri-DeSmedt, Nefeli Dimitra; Hizanidis, Johanne; Schöll, Eckehard; Hövel, Philipp; Provata, Astero

    2017-07-01

    The effects of attracting-nonlocal and reflecting connectivity are investigated in coupled Leaky Integrate-and-Fire (LIF) elements, which model the exchange of electrical signals between neurons. Earlier investigations have demonstrated that repulsive-nonlocal and hierarchical network connectivity can induce complex synchronization patterns and chimera states in systems of coupled oscillators. In the LIF system we show that if the elements are nonlocally linked with positive diffusive coupling on a ring network, the system splits into a number of alternating domains. Half of these domains contain elements whose potential stays near the threshold and they are interrupted by active domains where the elements perform regular LIF oscillations. The active domains travel along the ring with constant velocity, depending on the system parameters. When we introduce reflecting coupling in LIF networks unexpected complex spatio-temporal structures arise. For relatively extensive ranges of parameter values, the system splits into two coexisting domains: one where all elements stay near the threshold and one where incoherent states develop, characterized by multi-leveled mean phase velocity profiles.

  13. Why the moratorium on human-animal chimera research should not be lifted.

    Science.gov (United States)

    Moy, Alan

    2017-08-01

    The National Institutes of Health (NIH) announced its plans to lift its moratorium on funding research that involves injecting human embryonic stem cells into animal embryos, which would allow for the creation of part-human and part-animal organisms known as chimeras. The NIH allowed only one month to receive public comments in the midst of a presidential election campaign. Lifting the moratorium means that, for the first time, the federal government will begin spending taxpayer dollars on the creation and manipulation of new organisms that would blur the line between humans and animals. Interestingly, this government effort is creating an uncommon coalition between pro-life groups and animal rights activists that oppose this medical research on ethical grounds; the former seeking to ensure the welfare of human embryos and the latter seeking to protect the well-being of animals. Unlike the issue of abortion, this research is complex. Yet, it is important that the pro-life laity and clergy be adequately informed on some of the basic science and ethics that surround this research. To fully understand why this research is unethical and why the NIH is pursuing this particular research, it is important to understand the ethical tenets governing human-subject research and why secular scientists are pursuing this scientific field.

  14. Fragmentation studies with the CHIMERA detector at LNS in Catania: recent progress

    International Nuclear Information System (INIS)

    Pagano, A.; Alderighi, M.; Amorini, F.; Anzalone, A.; Arena, L.; Auditore, L.; Baran, V.; Bartolucci, M.; Berceanu, I.; Blicharska, J.; Brzychczyk, J.; Bonasera, A.; Borderie, B.; Bougault, R.; Bruno, M.; Cardella, G.; Cavallaro, S.; Chatterjee, M.B.; Chbihi, A.; Cibor, J.; Colonna, M.; D'Agostino, M.; Dayras, R.; De Filippo, E.; Di Toro, M.; Gawlikowicz, W.; Geraci, E.; Giustolisi, F.; Grzeszczuk, A.; Guazzoni, P.; Guinet, D.; Iacono-Manno, M.; Kowalski, S.; La Guidara, E.; Lanzano, G.; Lanzalone, G.; Le Neindre, N.; Li, S.; Lo Nigro, S.; Maiolino, C.; Majka, Z.; Manfredi, G.; Paduszynski, T.; Papa, M.; Petrovici, M.; Piasecki, E.; Pirrone, S.; Planeta, R.; Politi, G.; Pop, A.; Porto, F.; Rivet, M.F.; Rosato, E.; Rizzo, F.; Russo, S.; Russotto, P.; Sassi, M.; Sechi, G.; Simion, V.; Siwek-Wilczynska, K.; Skwira, I.; Sperduto, M.L.; Steckmeyer, J.C.; Swiderski, L.; Trifiro, A.; Trimarchi, M.; Vannini, G.; Vigilante, M.; Wieleczko, J.P.; Wilczynski, J.; Wu, H.; Xiao, Z.; Zetta, L.; Zipper, W.

    2004-01-01

    The new detector CHIMERA, in its final 4π configuration, has been installed at Laboratori Nazionali del Sud (LNS) in Catania in January 2003. Beams of different energies ranging from protons to Au ions were delivered by the Tandem and the Super Conducting Cyclotron for nuclear reaction studies, in agreement with the approval of the Scientific Advisory Committee of LNS. Recent experimental results confirm very low energy thresholds of the trigger (below 0.5 MeV/nucleon), ensured within a wide dynamical range. Good characteristics of identification of light charged particles and heavy fragments have been obtained by using three detection techniques: ΔE-E, ΔE-time of flight, and the Pulse-Shape discrimination method. We present results of recent analysis concerning the production of intermediate mass fragments (IMF) in semi-peripheral collisions. Our results combined with theoretical Boltzmann-Nordheim-Vlasov simulations clearly demonstrate the presence of very fast processes of IMF production in the overlapping region of the target and projectile nuclei during re-separation, i.e. in the time scale comparable with the collision time. Evidence for slower, sequential-like production of IMF's is also shown

  15. Allogeneic hematopoietic stem-cell transplantation for acute myeloid leukemia in remission

    DEFF Research Database (Denmark)

    Nagler, Arnon; Rocha, Vanderson; Labopin, Myriam

    2013-01-01

    Cyclophosphamide (Cy) combined with total-body irradiation (TBI) or with busulfan (Bu) are currently the most common myeloablative regimens used in allogeneic stem-cell transplantation (alloSCT) in adults with acute myelogenous leukemia (AML). Intravenous (IV) Bu has more predictable...

  16. Allogeneic mesenchymal precursor cells (MPCs): an innovative approach to treating advanced heart failure.

    Science.gov (United States)

    Westerdahl, Daniel E; Chang, David H; Hamilton, Michele A; Nakamura, Mamoo; Henry, Timothy D

    2016-09-01

    Over 37 million people worldwide are living with Heart Failure (HF). Advancements in medical therapy have improved mortality primarily by slowing the progression of left ventricular dysfunction and debilitating symptoms. Ultimately, heart transplantation, durable mechanical circulatory support (MCS), or palliative care are the only options for patients with end-stage HF. Regenerative therapies offer an innovative approach, focused on reversing myocardial dysfunction and restoring healthy myocardial tissue. Initial clinical trials using autologous (self-donated) bone marrow mononuclear cells (BMMCs) demonstrated excellent safety, but only modest efficacy. Challenges with autologous stem cells include reduced quality and efficacy with increased patient age. The use of allogeneic mesenchymal precursor cells (MPCs) offers an "off the shelf" therapy, with consistent potency and less variability than autologous cells. Preclinical and initial clinical trials with allogeneic MPCs have been encouraging, providing the support for a large ongoing Phase III trial-DREAM-HF. We provide a comprehensive review of preclinical and clinical data supporting MPCs as a therapeutic option for HF patients. The current data suggest allogeneic MPCs are a promising therapy for HF patients. The results of DREAM-HF will determine whether allogeneic MPCs can decrease major adverse clinical events (MACE) in advanced HF patients.

  17. On the Feasibility of Utilizing Allogeneic Bone Blocks for Atrophic Maxillary Augmentation

    Directory of Open Access Journals (Sweden)

    Alberto Monje

    2014-01-01

    Full Text Available Purpose. This systematic review was aimed at assessing the feasibility by means of survival rate, histologic analysis, and causes of failure of allogeneic block grafts for augmenting the atrophic maxilla. Material and Methods. A literature search was conducted by one reviewer in several databases. Articles were included in this systematic review if they were human clinical trials in which outcomes of allogeneic bone block grafts were studied by means of survival rate. In addition other factors were extracted in order to assess their influence upon graft failure. Results. Fifteen articles fulfilled the inclusion criteria and subsequently were analyzed in this systematic review. A total of 361 block grafts could be followed 4 to 9 months after the surgery, of which 9 (2.4% failed within 1 month to 2 months after the surgery. Additionally, a weighed mean 4.79 mm (95% CI: 4.51–5.08 horizontal bone gain was computed from 119 grafted sites in 5 studies. Regarding implant cumulative survival rate, the weighed mean was 96.9% (95% CI: 92.8–98.7%, computed from 228 implants over a mean follow-up period of 23.9 months. Histologic analysis showed that allogeneic block grafts behave differently in the early stages of healing when compared to autogenous block grafts. Conclusion. Atrophied maxillary reconstruction with allogeneic bone block grafts represents a reliable option as shown by low block graft failure rate, minimal resorption, and high implant survival rate.

  18. Specific Factors Influence the Success of Autologous and Allogeneic Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Thissiane L. Gonçalves

    2009-01-01

    Full Text Available Successful hematopoietic stem cell transplantation (HSCT, both autologous and allogeneic, requires a rapid and durable engraftment, with neutrophil (>500/µL and platelet (>20,000/µL reconstitution. Factors influencing engraftment after autologous or allogeneic HSCT were investigated in 65 patients: 25 autologous peripheral stem cell transplantation (PBSCT and 40 allogeneic bone marrow transplantation (BMT patients. The major factor affecting engraftment was the graft source for HSCT. Neutrophil and platelet recovery were more rapid in autologous PBSCT than in allogeneic BMT [neutrophil occurring in median on day 10.00 (09.00/11.00 and 19.00 (16.00/23.00 and platelet on day 11.00 (10.00/13.00 and 21.00 (18.00/25.00, respectively; p < 0.0001]. The type of disease also affected engraftment, where multiple myeloma (MM and lymphoma showed faster engraftment when compared with leukemia, syndrome myelodysplastic (SMD and aplastic anemia (AA and MM presented the best overall survival (OS in a period of 12 months. Other factors included the drug used in the conditioning regimen (CR, where CBV, melphalan (M-200 and FluCy showed faster engraftment and M-200 presented the best OS, in a period of 12 months and age, where 50–59 years demonstrated faster engraftment. Sex did not influence neutrophil and platelet recovery.

  19. The Role of Allogeneic Transplantation in the Treatment of Multiple Myeloma.

    Science.gov (United States)

    Majolino, I

    1998-01-01

    In multiple myeloma (MM) attempts to improve upon the results of standard melphalanpredisone with other conventional dose drug combinations, have generally been unsuccessful, producing only minor improvements in response rate, with little effect on survival. The only treatment capable of producing a dramatic change in response and life expectancy is high-dose chemo-radiotherapy followed by stem cell transplantation. However, after autologous transplant relapse will almost inevitably occur, and freedom from recurrence curves show no plateau in most studies. Besides the resistance of the disease to chemotherapy, another possible explanation is tumor contamination of the graft. This is one major advantage of allogeneic transplantation over autologous, the other being an immune mediated mechanism of tumor suppression in part related to GVHD. Application of allogeneic transplantation to MM has met a number of obstacles, but is now entering a phase of reappraisal, due in part to a tendency to earlier transplantation, in part to the use of novel technologies such as allogeneic peripheral blood stem cells instead of marrow. The goal should be the reduction of transplant related deaths, to better exploit the higher eradication potential of allogeneic cell therapies. The most intriguing perspectives are those related to immune manipulation of recipient and/or donor.

  20. Gastrointestinal toxicity, systemic inflammation, and liver biochemistry in allogeneic hematopoietic stem cell transplantation

    DEFF Research Database (Denmark)

    Jordan, Karina; Pontoppidan, Peter; Uhlving, Hilde Hylland

    2017-01-01

    Liver toxicity is frequently seen in relation to allogeneic hematopoietic stem cell transplantation (HSCT), but pathogenesis and the risk factors are poorly understood. The purpose of this study was to investigate associations between liver toxicity, gastrointestinal toxicity, and levels of immun...

  1. Novel therapies and their integration into allogeneic stem cell transplant for chronic lymphocytic leukemia.

    Science.gov (United States)

    Jaglowski, Samantha M; Byrd, John C

    2012-01-01

    Over the past decade, numerous advances have been made in elucidating the biology of and improving treatment for chronic lymphocytic leukemia (CLL). These studies have led to identification of select CLL patient groups that generally have short survival dating from time of treatment or initial disease relapse who benefit from more aggressive therapeutic interventions. Allogeneic transplantation represents the only potentially curative option for CLL, but fully ablative regimens applied in the past have been associated with significant morbidity and mortality. Reduced-intensity preparative regimens has made application of allogeneic transplant to CLL patients much more feasible and increased the number of patients proceeding to this modality. Arising from this has been establishment of guidelines where allogeneic stem cell transplantation should be considered in CLL. Introduction of new targeted therapies with less morbidity, which can produce durable remissions has the potential to redefine where transplantation is initiated in CLL. This review briefly summarizes the field of allogeneic stem cell transplant in CLL and the interface of new therapeutics with this modality. Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  2. Gastrointestinal toxicity, systemic inflammation, and liver biochemistry in allogeneic hematopoietic stem cell transplantation

    Science.gov (United States)

    Liver toxicity is frequently seen in relation to allogeneic hematopoietic stem cell transplantation (HSCT), but pathogenesis and the risk factors are poorly understood. The purpose of this study was to investigate associations between liver toxicity, gastrointestinal toxicity, and levels of immune-r...

  3. Blood management in total hip replacement: an analysis of factors associated with allogenic blood transfusion.

    Science.gov (United States)

    Wong, Samuel; Tang, Howard; de Steiger, Richard

    2015-06-01

    The aim of this study was to audit the blood transfusion practice throughout the Epworth Healthcare Hospitals for patients undergoing primary total hip replacement (THR). We determined if blood-saving techniques were having an impact on the risk of allogenic blood transfusion and which patients were at risk of receiving allogenic blood transfusion. This study uses a retrospective audit of 787 patients who had undergone primary THR surgery at three Melbourne hospitals: Epworth Richmond, Epworth Eastern and Epworth Freemasons in 2010. Patient demographics, transfusion requirements and blood-conserving techniques were recorded. One hundred and eighty (23%) patients received allogenic blood transfusion and 18 (2.3%) patients received autologous blood transfusion. On multivariate analysis, preoperative anaemia (odds ratio (OR) 4.7, P blood transfusion. Use of spinal anaesthetic was found to be associated with lower risk of transfusion (OR 0.6, P = 0.0180) compared with general anaesthetic alone. Cell saver, acute normovolaemic haemodilution and re-infusion drain tube usage did not have a significant impact on reducing the risk of allogenic blood transfusion. Identification of patients at risk of blood transfusion, correction of preoperative anaemia and a restrictive transfusion policy are important factors to consider in effective perioperative blood management. © 2015 Royal Australasian College of Surgeons.

  4. Preoperative Acute Normovolemic Hemodilution for Minimizing Allogeneic Blood Transfusion: A Meta-Analysis.

    Science.gov (United States)

    Zhou, Xuelong; Zhang, Chenjing; Wang, Yin; Yu, Lina; Yan, Min

    2015-12-01

    Previous studies have evaluated the efficacy of preoperative acute normovolemic hemodilution (PANH) in reducing the need for allogeneic blood transfusion. However, the results to date have been controversial. In this study, we sought to reassess the efficacy and safety of PANH based on newly emerging evidence. Medline, EMBASE, ISI Web of Knowledge, and Cochrane Central Register of Controlled Trials databases were searched using the key words "hemodilution," "autotransfusion," or "hemorrhage" to retrieve all randomized controlled trials examining the benefits of PANH compared with control patients not undergoing PANH in any type of surgery. Sixty-three studies involving 3819 patients were identified. The risk of requiring an allogeneic blood transfusion and the overall volume of allogeneic red blood cell transfused during the perioperative period were reduced in the PANH group compared with the control group (relative risk, 0.74; 95% confidence interval, 0.63 to 0.88; P = 0.0006; weighted mean difference, -0.94 units; 95% confidence interval, -1.27 to -0.61 units; P transfusion. Perioperative blood loss, adverse events, and the length of hospitalization were comparable between these groups. Although these results suggest that PANH is effective in reducing allogeneic blood transfusion, we identified significant heterogeneity and publication bias, which raises concerns about the true efficacy of PANH.

  5. Differential diagnosis of skin lesions after allogeneic haematopoietic stem cell transplantation

    NARCIS (Netherlands)

    Canninga-van Dijk, MR; Sanders, CJ; Verdonck, LF; Fijnheer, R; van den Tweel, JG

    Allogeneic haematopoietic stem cell transplantation (i.e. bone marrow or peripheral blood stem cell transplantation) is a common procedure in the treatment of various haematological disorders such as aplastic anaemia, (pre)leukaemias, some malignant lymphomas, multiple myeloma and immunodeficiency

  6. Unrelated allogeneic stem-cell transplantation in adult patients – 10-year experience

    Directory of Open Access Journals (Sweden)

    Jožef Pretnar

    2012-12-01

    Conclusion: Unrelated allogeneic stem-cell transplantation is suitable for acute myeloblastic leukemias with unfavorable risk factors. However, results in acute lymphoblastic leukemia are worse. Unrelated transplantation is not efficient as salvage treatment for patients with recurrent disease after autologous transplantation or chemotherapy- resistant relapse.

  7. The risks of using allogeneic cell lines for vaccine production : The example of Bovine Neonatal Pancytopenia

    NARCIS (Netherlands)

    Benedictus, Lindert; Bell, Charlotte R

    2017-01-01

    INTRODUCTION: Bovine neonatal pancytopenia (BNP) is a hemorrhagic disease that emerged in calves across Europe in 2007. Its occurrence is attributed to immunization of the calf's mother with a vaccine produced using an allogeneic cell line. Vaccine-induced alloantibodies specific for

  8. Graft-versus-host disease and graft-versus-tumor effects after allogeneic hematopoietic cell transplantation

    DEFF Research Database (Denmark)

    Storb, Rainer; Gyurkocza, Boglarka; Storer, Barry E

    2013-01-01

    We designed a minimal-intensity conditioning regimen for allogeneic hematopoietic cell transplantation (HCT) in patients with advanced hematologic malignancies unable to tolerate high-intensity regimens because of age, serious comorbidities, or previous high-dose HCT. The regimen allows the pures...

  9. Titanium implant insertion into dog alveolar ridges augmented by allogenic material

    DEFF Research Database (Denmark)

    Pinholt, E M; Haanaes, H R; Donath, K

    1994-01-01

    The purpose of this investigation was to evaluate whether titanium endosseous implants would osseointegrate in dog alveolar ridges augmented by allogenic material. In 8 dogs en bloc resection, including 2 pre-molars, was performed bilaterally in the maxilla and the mandible. After a healing period...

  10. Prolonged Survival of Subcutaneous Allogeneic Islet Graft by Donor Chimerism without Immunosuppressive Treatment

    Directory of Open Access Journals (Sweden)

    Brend Ray-Sea Hsu

    2017-01-01

    Full Text Available The aim of this study was to investigate whether tolerance-induced protection of islets in the renal subcapsular space can also prevent subcutaneous allogeneic islets from being rejected. We used bone marrow stem cells from C57BL/6 (H2b mice to construct donor chimerism in conditioned diabetic BALB/c (H2d mice and investigated the effect of donor chimerism on engraftment and survival of subcutaneously transplanted allogeneic islets in streptozotocin-induced diabetic mice. We also studied the anti-inflammatory effect of mesenchymal stem cell on islet engraftment. Full but not low-grade or no donor chimerism was associated with successful engraftment of allogeneic islets and restoration of normoglycemia in the treated diabetic mice. The temporary hyperglycemia was 11 ± 1 versus 19 ± 5 days (p<0.05 for the mice with full donor chimerism with transplanted islets in the renal subcapsular space versus the subcutaneous space, respectively. Cotransplantation of mesenchymal stem cell did not enhance alloislet engraftment. Full multilineage donor chimerism was associated with a higher transient expansion of CD11b+ and Gr-1+ myeloid progenitor cells and effector memory CD4 and CD8 T cells. In conclusion, full donor chimerism protected both renal subcapsular and subcutaneous allogeneic islets in this rodent transplantation model.

  11. The effect of allogenic versus autologue mesenchymal stem cells in bone reconstructio

    DEFF Research Database (Denmark)

    Jensen, Stefan; Overgaard, Søren; Ding, Ming

    2008-01-01

    with allogenic MSC (group#3) proved to have a significant higher mean SFE (Fisher's LSD-test). The other groups (#1 and #2) had a slightly higher mean SFE (Table 2). Discussion and Conclusion: There are shown two interesting things in this minor pilot-study. There is a trend showing, that the use of MSC has...

  12. Platelet-rich-plasmapheresis for minimising peri-operative allogeneic blood transfusion.

    Science.gov (United States)

    Carless, Paul A; Rubens, Fraser D; Anthony, Danielle M; O'Connell, Dianne; Henry, David A

    2011-03-16

    Concerns regarding the safety of transfused blood have generated considerable enthusiasm for the use of technologies intended to reduce the use of allogeneic blood (blood from an unrelated donor). Platelet-rich plasmapheresis (PRP) offers an alternative approach to blood conservation. To examine the evidence for the efficacy of PRP in reducing peri-operative allogeneic red blood cell (RBC) transfusion, and the evidence for any effect on clinical outcomes such as mortality and re-operation rates. We identified studies by searching MEDLINE (1950 to 2009), EMBASE (1980 to 2009), The Cochrane Library (Issue 1, 2009), the Internet (to March 2009) and the reference lists of published articles, reports, and reviews. Controlled parallel group trials in which adult patients, scheduled for non-urgent surgery, were randomised to PRP, or to a control group which did not receive the intervention. Primary outcomes measured were: the number of patients exposed to allogeneic RBC transfusion, and the amount of RBC transfused. Other outcomes measured were: the number of patients exposed to allogeneic platelet transfusions, fresh frozen plasma, and cryoprecipitate, blood loss, re-operation for bleeding, post-operative complications (thrombosis), mortality, and length of hospital stay. Treatment effects were pooled using a random-effects model. Trial quality was assessed using criteria proposed by Schulz et al (Schulz 1995). Twenty-two trials of PRP were identified that reported data for the number of patients exposed to allogeneic RBC transfusion. These trials evaluated a total of 1589 patients. The relative risk (RR) of exposure to allogeneic blood transfusion in those patients randomised to PRP was 0.73 (95%CI 0.59 to 0.90), equating to a relative risk reduction (RRR) of 27% and a risk difference (RD) of 19% (95%CI 10% to 29%). However, significant heterogeneity of treatment effect was observed (p transfused (weighted mean difference [WMD] -0.69, 95%CI -1.93 to 0.56 units). Trials

  13. Chondrocytic Potential of Allogenic Mesenchymal Stem Cells Transplanted without Immunosuppression to Regenerate Physeal Defect in Rabbits

    Directory of Open Access Journals (Sweden)

    P. Gál

    2007-01-01

    Full Text Available Mesenchymal stem cells (MSCs from bone marrow are multipotent cells capable of forming cartilage, bone, and other connective tissues. The objective of this study was to determine whether the use of allogenic mesenchymal stem cells could functionally heal a defect in the distal femoral physis in rabbits without the use of immunosuppressive therapy. A iatrogenic defect was created in the lateral femoral condyle of thirty-two New Zealand white rabbits, 7 weeks old, weighing 2.25 ± 0.24 kg. Each defect, 3.5 mm in width and 12 mm in length, in the right distal femoral physis was treated with allogenic mesenchymal stem cells in new composite hyaluronate/collagen type I/fibrin scaffold. The healing response was evaluated radiographically, by MRI (three weeks and four months after implantation and also histologically, by Pearl’s reaction and with immunofluorescence (four months after implantation. The results were compared with the data for the control defects (without stem cell implantation in left distal femoral physes. On average, right femurs with a damaged distal physis and transplanted MSCs grew more in length (0.55 ± 0.21 cm compared with left femurs with a physeal defect without stem cell transplantation (0.46 ± 0.23 cm. Valgus deformity of right femurs with a physeal defect and transplanted MSCs was mild (0.2 ± 0.1 °. On the contrary, left femurs with a physeal defect without transplanted MSCs showed a significant valgus deformity (2.7 ± 1.6 °. For defects treated with allogenic mesenchymal stem cell implants, no adverse immune response and implant rejection were detected in this model. Histologically, no lymphocytic infiltration occurred. At four months after transplantation, hyaline cartilage had formed throughout the defects treated with allogenic MSCs. Labelled mesenchymal stem cells/differentiated chondrocytes were detected in the physeal defects based on magnetic resonance imaging and immunofluorescence. The results of this study

  14. Radiation damage and induced tetraploidy in mulberry (Morus alba L.)

    International Nuclear Information System (INIS)

    Katagiri, K.

    1976-01-01

    Vigorously growing mulberry shoots were exposed to 5 kR of gamma rays at the rate of 0.2 kR/hr and 5.0 kR/hr and successively pruned three times in two growing seasons. The most radiosensitive part of both the apical and axillary meristems was the second cell layer. The younger axillary bud primordia were more sensitive to radiation then the older ones. Recovery from radiation damage was assumed to be from the flank meristem in the shoot apex. The frequency of mutations was much lower than that of tetraploidy. Among the tetraploids 50% were 2-4-4 chimeras. (author)

  15. Achieving an early pregnancy following allogeneic uterine transplantation in a rabbit model.

    Science.gov (United States)

    Saso, Srdjan; Petts, Gemma; David, Anna L; Thum, Meen-Yau; Chatterjee, Jayanta; Vicente, Jose S; Marco-Jimenez, Francisco; Corless, David; Boyd, Michael; Noakes, David; Lindsay, Iain; Del Priore, Giuseppe; Ghaem-Maghami, Sadaf; Smith, J Richard

    2015-02-01

    Uterine transplantation (UTx) has been proposed as a treatment option for women diagnosed with absolute uterine factor infertility (AUFI). The goal of UTx remains achieving pregnancy and live birth of a healthy neonate following allogeneic UTx. Our aim was to assess whether fertility was possible following allogeneic uterine transplantation (UTx), when the recipient had demonstrated long-term survival and had been administered immunosuppression. Nine allogeneic UTx in New Zealand White rabbits were performed using a pre-determined protocol. Tacrolimus was the immunosuppressant selected. Embryos were transferred into both cornua of the sole living recipient via a mini-midline laparotomy. The pregnancy was monitored with regular reproductive profiles and serial trans-abdominal ultrasound to measure conceptus growth (gestation sac and crown rump length (CRL)). In the sole surviving doe a gestation sac was visualised on ultrasound from Day 9 (D9) after embryo transfer. Gestation sac diameter and CRL increased from D9 to D16 but by D18 the gestation sac had reduced in size. The fetus was no longer visible, suggesting fetal resorption had occurred. Subsequent scans on D22 and D25 did not demonstrate a gestation sac. Scheduled necropsy on D27 and histopathology confirmed evidence of a gravid uterus and presence of a gestational sac. A single episode of acute rejection occurred on D13. Pregnancy was achieved after rabbit allogeneic UTx but serial ultrasound suggested that fetal demise occurred prior to scheduled necropsy. The study represents only the third example of conception and pregnancy following an animal allogeneic UTx. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. Outcomes of allogeneic hematopoietic stem cell transplantation for lymphomas: a single-institution experience

    Directory of Open Access Journals (Sweden)

    Mira Romany Massoud

    Full Text Available ABSTRACT Introduction: Allogeneic hematopoietic stem cell transplantation offers the opportunity for extended survival in patients with Hodgkin's and non-Hodgkin lymphomas who relapsed after, or were deemed ineligible for, autologous transplantation. This study reports the cumulative experience of a single center over the past 14 years aiming to define the impact of patient, disease, and transplant-related characteristics on outcomes. Methods: All patients with histologically confirmed diagnosis of Hodgkin's or non-Hodgkin lymphomas who received allogeneic transplantation from 2000 to 2014 were retrospectively studied. Results: Forty-one patients were reviewed: 10 (24% had Hodgkin's and 31 (76% had non-Hodgkin lymphomas. The median age was 50 years and 23 (56% were male. The majority of patients (68% had had a prior autologous transplantation. At the time of allogeneic transplantation, 18 (43% patients were in complete and seven (17% were in partial remission. Most (95% patients received reduced-intensity conditioning, 49% received matched sibling donor grafts, 24% matched-unrelated donor grafts, and 27% received double umbilical cord blood grafts. The 100-day treatment-related mortality rate was 12%. After a median duration of follow up of 17.1 months, the median progression-free and overall survival was 40.5 and 95.8 months, respectively. On multivariate analysis, patients who had active disease at the time of transplant had inferior survival. Conclusions: Allogeneic transplantation results extend survival in selected patients with relapsed/refractory Hodgkin's and non-Hodgkin lymphomas with low treatment-related mortality. Patients who have active disease at the time of allogeneic transplantation have poor outcomes.

  17. Autologous Dendritic Cells Pulsed with Allogeneic Tumor Cell Lysate in Mesothelioma: From Mouse to Human.

    Science.gov (United States)

    Aerts, Joachim G J V; de Goeje, Pauline L; Cornelissen, Robin; Kaijen-Lambers, Margaretha E H; Bezemer, Koen; van der Leest, Cor H; Mahaweni, Niken M; Kunert, André; Eskens, Ferry A L M; Waasdorp, Cynthia; Braakman, Eric; van der Holt, Bronno; Vulto, Arnold G; Hendriks, Rudi W; Hegmans, Joost P J J; Hoogsteden, Henk C

    2018-02-15

    Purpose: Mesothelioma has been regarded as a nonimmunogenic tumor, which is also shown by the low response rates to treatments targeting the PD-1/PD-L1 axis. Previously, we demonstrated that autologous tumor lysate-pulsed dendritic cell (DC) immunotherapy increased T-cell response toward malignant mesothelioma. However, the use of autologous tumor material hampers implementation in large clinical trials, which might be overcome by using allogeneic tumor cell lines as tumor antigen source. The purpose of this study was to investigate whether allogeneic lysate-pulsed DC immunotherapy is effective in mice and safe in humans. Experimental Design: First, in two murine mesothelioma models, mice were treated with autologous DCs pulsed with either autologous or allogeneic tumor lysate or injected with PBS (negative control). Survival and tumor-directed T-cell responses of these mice were monitored. Results were taken forward in a first-in-human clinical trial, in which 9 patients were treated with 10, 25, or 50 million DCs per vaccination. DC vaccination consisted of autologous monocyte-derived DCs pulsed with tumor lysate from five mesothelioma cell lines. Results: In mice, allogeneic lysate-pulsed DC immunotherapy induced tumor-specific T cells and led to an increased survival, to a similar extent as DC immunotherapy with autologous tumor lysate. In the first-in-human clinical trial, no dose-limiting toxicities were established and radiographic responses were observed. Median PFS was 8.8 months [95% confidence interval (CI), 4.1-20.3] and median OS not reached (median follow-up = 22.8 months). Conclusions: DC immunotherapy with allogeneic tumor lysate is effective in mice and safe and feasible in humans. Clin Cancer Res; 24(4); 766-76. ©2017 AACR . ©2017 American Association for Cancer Research.

  18. Management of chimera and in vitro mutagenesis for development of new flower color/shape and chlorophyll variegated mutants in chrysanthemum

    Energy Technology Data Exchange (ETDEWEB)

    Datta, S.K. [CSIR, Madhyamgram Experimental Farm, Bose Institute, Kolkata (India)], E-mail: subodhskdatta@rediffmail.com; Chakrabarty, D [Floriculture Laboratory, National Botanical Research Institute, Lucknow (India)

    2008-07-01

    Induced mutagenesis has played a major role in the development of many new flower color/shape mutant varieties in ornamentals. The main bottleneck with vegetatively propagated plants is that the mutation appears as a chimera whether developed through bud sport or through induced mutation. The size of the mutant sector varies from a narrow streak on a petal to the entire flower and from a portion of a branch to the entire branch. When a portion of a branch or entire branch is mutated, the mutant tissue can be isolated; on the other hand, a small sector of a mutated branch or flower cannot be isolated using the available conventional propagation techniques. A novel technique has been standardized in our laboratory for the management of chimeric tissues through direct shoot regeneration from chrysanthemum florets. 'Kasturba Gandhi', a large white flowered chrysanthemum, developed few chimeric yellow florets due to spontaneous mutation. Using in vitro protocol new yellow florets were established in pure form. In vitro mutagenesis experiments were conducted treating ray florets of chrysanthemum cultivars using gamma rays. Induced chimeric yellow, white, light yellow, light mauve and dark mauve floret color sectors and chlorophyll variegation in leaves of cv. 'Maghi' (with mauve floret and green leaves) have been established in pure form. Gamma ray induced sectorial yellow florets of cv. 'Lilith' (white floret) and yellow ray florets in both the cvs. 'Purnima' (with white florets) and 'Colchi Bahar' (with red florets) have been isolated in pure form through in vitro management. Induced sectorial flower color/shape mutations in cvs. 'Puja', 'Lalima', 'Flirt', 'Maghi' and 'Sunil' have been isolated in pure form through in vitro culture. Gamma radiation procedure and tissue culture techniques have been optimized to regenerate plants from stem internodes, stem node, shoot tip and ray florets. Present technique has opened a new way for isolating new flower color

  19. Oral cryotherapy for the prevention of high-dose melphalan-induced stomatitis in allogeneic hematopoietic stem cell transplant recipients.

    Science.gov (United States)

    Aisa, Yoshinobu; Mori, Takehiko; Kudo, Masumi; Yashima, Tomoko; Kondo, Sakiko; Yokoyama, Akihiro; Ikeda, Yasuo; Okamoto, Shinichiro

    2005-04-01

    The purpose of this study was to evaluate the efficacy of oral cryotherapy to prevent high-dose melphalan-induced stomatitis. Eighteen consecutive recipients of allogeneic hematopoietic stem cell transplant conditioned with high-dose melphalan (140 mg/m2) in combination with fludarabine alone or with fludarabine and additional chemotherapy or radiation were enrolled. The severity of stomatitis was graded according to the National Cancer Institute Common Toxicity Criteria. Patients were kept on oral cryotherapy using ice chips and ice-cold water shortly before, during, and for additional 90 min after completion of melphalan administration. Only two of 18 patients (11.1%) developed grade 2 or 3 stomatitis while six of seven patients in the historical control developed it (85.7%; P=0.001). These results suggested that oral cryotherapy could effectively prevent stomatitis caused by high-dose melphalan, and we recommend that it should be incorporated into the conditioning regimen with high-dose melphalan.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    by their inefficient functional expression in vitro. In the present study we have characterized and compared the pharmacological properties displayed by α6β4 and α6β4β3 nicotinic acetylcholine receptors assembled in tsA201 cells from the classical α6/α3 chimera (C1) and two novel α6/α3 chimeras (C6F223L and C16F223L...... should be made keeping the molecular modifications in the α6 surrogate subunits in mind, this study sheds light on the pharmacological properties of α6β4⁎ nicotinic acetylcholine receptors and demonstrates the applicability of the C6F223L and C16F223L chimeras for studies of these receptors....

  1. The Crystal Structure of a Maxi/Mini-Ferritin Chimera Reveals Guiding Principles for the Assembly of Protein Cages

    Energy Technology Data Exchange (ETDEWEB)

    Cornell, Thomas A. [Department; Division; Srivastava, Yogesh [Genome; Jauch, Ralf [Genome Institute of Singapore, Singapore; Genome; Fan, Rongli [Division; Orner, Brendan P. [Department; Division

    2017-07-19

    Cage proteins assemble into nanoscale structures with large central cavities. They play roles, including those as virus capsids and chaperones, and have been applied to drug delivery and nanomaterials. Furthermore, protein cages have been used as model systems to understand and design protein quaternary structure. Ferritins are ubiquitous protein cages that manage iron homeostasis and oxidative damage. Two ferritin subfamilies have strongly similar tertiary structure yet distinct quaternary structure: maxi-ferritins normally assemble into 24-meric, octahedral cages with C-terminal E-helices centered around 4-fold symmetry axes, and mini-ferritins are 12-meric, tetrahedral cages with 3-fold axes defined by C-termini lacking E-domains. To understand the role E-domains play in ferritin quaternary structure, we previously designed a chimera of a maxi-ferritin E-domain fused to the C-terminus of a mini-ferritin. The chimera is a 12-mer cage midway in size between those of the maxi- and mini-ferritin. The research described herein sets out to understand (a) whether the increase in size over a typical mini-ferritin is due to a frozen state where the E-domain is flipped out of the cage and (b) whether the symmetrical preference of the E-domain in the maxi-ferritin (4-fold axis) overrules the C-terminal preference in the mini-ferritin (3-fold axis). With a 1.99 Å resolution crystal structure, we determined that the chimera assembles into a tetrahedral cage that can be nearly superimposed with the parent mini-ferritin, and that the E-domains are flipped external to the cage at the 3-fold symmetry axes.

  2. Defining the biomechanical and biological threshold of murine mild traumatic brain injury using CHIMERA (Closed Head Impact Model of Engineered Rotational Acceleration).

    Science.gov (United States)

    Namjoshi, Dhananjay R; Cheng, Wai Hang; Bashir, Asma; Wilkinson, Anna; Stukas, Sophie; Martens, Kris M; Whyte, Tom; Abebe, Zelalem A; McInnes, Kurt A; Cripton, Peter A; Wellington, Cheryl L

    2017-06-01

    CHIMERA (Closed Head Impact Model of Engineered Rotational Acceleration) is a recently described animal model of traumatic brain injury (TBI) that primarily produces diffuse axonal injury (DAI) characterized by white matter inflammation and axonal damage. CHIMERA was specifically designed to reliably generate a variety of TBI severities using precise and quantifiable biomechanical inputs in a nonsurgical user-friendly platform. The objective of this study was to define the lower limit of single impact mild TBI (mTBI) using CHIMERA by characterizing the dose-response relationship between biomechanical input and neurological, behavioral, neuropathological and biochemical outcomes. Wild-type male mice were subjected to a single CHIMERA TBI using six impact energies ranging from 0.1 to 0.7J, and post-TBI outcomes were assessed over an acute period of 14days. Here we report that single TBI using CHIMERA induces injury dose- and time-dependent changes in behavioral and neurological deficits, axonal damage, white matter tract microgliosis and astrogliosis. Impact energies of 0.4J or below produced no significant phenotype (subthreshold), 0.5J led to significant changes for one or more phenotypes (threshold), and 0.6 and 0.7J resulted in significant changes in all outcomes assessed (mTBI). We further show that linear head kinematics are the most robust predictors of duration of unconsciousness, severity of neurological deficits, white matter injury, and microgliosis following single TBI. Our data extend the validation of CHIMERA as a biofidelic animal model of DAI and establish working parameters to guide future investigations of the mechanisms underlying axonal pathology and inflammation induced by mechanical trauma. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  3. Newspaper coverage of human-pig chimera research: A qualitative study on select media coverage of scientific breakthrough.

    Science.gov (United States)

    Hagan-Brown, Abena; Favaretto, Maddalena; Borry, Pascal

    2017-07-01

    A recently published article in the journal Cell by scientists from the Salk Institute highlighted the successful integration of stem cells from humans in pig embryos. This marks the first step toward the goal of growing human organs in animals for transplantation. There has, to date, been no research performed on the presentation of this breakthrough in the media. We thus assessed early newspaper coverage of the chimera study, looking into the descriptions as well as the benefits and concerns raised by the study mentioned by newspaper sources. We looked at newspaper coverage of the human-pig chimera study in the two weeks after the publication of the article describing the breakthrough in Cell. This time period spanned from January 26 to February 9, 2017. We used the LexisNexis Academic database and identified articles using the search string "hybrid OR chimera AND pig OR human OR embryo." The relevant articles were analyzed using qualitative content analysis. Two researchers openly coded the articles independently using themes that emerged from the raw texts. Our search yielded 31 unique articles, after extensive screening for relevance and duplicates. Through our analysis, we were able to identify several themes in a majority of the texts. Almost every article gave descriptive information about the chimera experiment with details about the study findings. All of the articles mentioned the benefits of the study, citing both immediate- and long-term goals, which included creating transplantable human organs, disease and drug development, and personalized medicine, among others. Some of the articles highlighted some ethical, social, and health concerns that the study and its future implications pose. Many of the articles also offered reassurances over the concerns brought up by the experiment. Our results appeared to align with similar research performed on the media representation of sensitive scientific news coverage. We also explored the inconsistency between

  4. A chimera grid scheme. [multiple overset body-conforming mesh system for finite difference adaptation to complex aircraft configurations

    Science.gov (United States)

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

    1983-01-01

    A mesh system composed of multiple overset body-conforming grids is described for adapting finite-difference procedures to complex aircraft configurations. In this so-called 'chimera mesh,' a major grid is generated about a main component of the configuration and overset minor grids are used to resolve all other features. Methods for connecting overset multiple grids and modifications of flow-simulation algorithms are discussed. Computational tests in two dimensions indicate that the use of multiple overset grids can simplify the task of grid generation without an adverse effect on flow-field algorithms and computer code complexity.

  5. Particle identification method in the CsI(Tl) scintillator used for the CHIMERA 4 pi detector

    CERN Document Server

    Alderighi, M; Basssini, R; Berceanu, I; Blicharska, J; Boiano, C; Borderie, B; Bougault, R; Bruno, M; Cali, C; Cardella, G; Cavallaro, S; D'Agostino, M; D'andrea, M; Dayras, R; De Filippo, E; Fichera, F; Geraci, E; Giustolisi, F; Grzeszczuk, A; Guardone, N; Guazzoni, P; Guinet, D; Iacono-Manno, M; Kowalski, S; La Guidara, E; Lanchais, A L; Lanzalone, G; Lanzanò, G; Le Neindre, N; Li, S; Maiolino, C; Majka, Z; Manfredi, G; Nicotra, D; Paduszynski, T; Pagano, A; Papa, M; Petrovici, C M; Piasecki, E; Pirrone, S; Politi, G; Pop, A; Porto, F; Rivet, M F; Rosato, E; Sacca, G; Sechi, G; Simion, V; Sperduto, M L; Steckmeyer, J C; Trifiró, A; Trimarchi, M; Urso, S; Vannini, G; Vigilante, M; Wilczynski, J; Wu, H; Xiao, Z; Zetta, L; Zipper, W

    2002-01-01

    The charged particle identification obtained by the analysis of signals coming from the CsI(Tl) detectors of the CHIMERA 4 pi heavy-ion detector is presented. A simple double-gate integration method, with the use of the cyclotron radiofrequency as reference time, results in low thresholds for isotopic particle identification. The dependence of the identification quality on the gate generation timing is discussed. Isotopic identification of light ions up to Beryllium is clearly seen. For the first time also the identification of Z=5 particles is observed. The identification of neutrons interacting with CsI(Tl) by (n,alpha) and (n,gamma) reactions is also discussed.

  6. The Fourth Nagoya International Blood and Marrow Transplantation Symposium: new horizons in allogeneic hematopoietic cell transplantation--2001 revolution.

    Science.gov (United States)

    Sao, Hiroshi; Morishita, Yoshihisa

    2002-02-01

    In this symposium, we saw new horizons in allogeneic transplantation. Are these truly revolutionary? We do not yet know the answer. However, there is no question about the importance of allogeneic T cells. T cells are much more powerful than any pharmacological drug man has ever generated. The question is, how do we take the most advantage of their potential. Every participant was encouraged to search for good answers to this question until the next meeting.

  7. Comparisons Between Allogeneic Peripheral Blood Stem Cell Transplantation and Allogeneic Bone Marrow Transplantation in Adult Hematologic Disease: A Single Center Experience

    Directory of Open Access Journals (Sweden)

    Yi-Chang Liu

    2003-11-01

    Full Text Available This retrospective study compared the outcomes in 32 adult patients with hematologic diseases (acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, myelodysplastic syndrome, severe aplastic anemia who received allogeneic bone marrow transplantation (BMT, n = 14; median age, 28 years or allogeneic peripheral blood stem cell transplantation (PBSCT, n = 18; median age, 29 years from human leukocyte antigen-identical sibling donors. Median follow-up was 58 months in BMT recipients and 18 months in PBSCT recipients. Neutrophil (median, Day 8 vs Day 13, p < 0.001 and platelet engraftment (median, Day 9 vs Day 17, p < 0.001 was faster in the PBSCT group than in the BMT group. Patients receiving PBSCT required less platelet transfusion than those receiving BMT (median, 54 units vs 144 units, p < 0.001, but there was no significant difference in red cell transfusion. At 100 days, there was no difference in the incidence of acute graft-versus-host disease (GVHD (42.9% vs 33.3%, p = 0.72 or grade II-IV acute GVHD (14.3% vs 5.6%, p = 0.57, and there was no difference in the cumulative incidence of chronic GVHD (20% vs 33.3%, p = 0.67. No chronic GVHD was noted in any relapsed patients (BMT, 5; PBSCT, 3, and no patients with chronic GVHD during follow-up had a relapse. Relapse was the most frequent cause of death in both groups (BMT, 5/9, 55.6%; PBSCT, 3/4, 75%; p = 0.25; all relapses occurred within 1 year after transplantation. Overall survival was significantly better in the PBSCT group (35.7% vs 77.8%, p = 0.029, but this difference was lost if only hematologic malignancies were analyzed (30.8% vs 63.6%, p = 0.20. Our results are similar to those reported previously, with faster neutrophil and platelet engraftment and less severe acute GVHD and extensive chronic GVHD with PBSCT. Allogeneic PBSCT is a feasible and beneficial alternative to allogeneic BMT in adult hematologic disease.

  8. Comparison of autogeneic and allogeneic natural killer cells immunotherapy on the clinical outcome of recurrent breast cancer

    Directory of Open Access Journals (Sweden)

    Liang S

    2017-08-01

    Full Text Available Shuzhen Liang,1,2 Kecheng Xu,1,2 Lizhi Niu,1,2 Xiaohua Wang,1 Yingqing Liang,1 Mingjie Zhang,3 Jibing Chen,1,2 Mao Lin1,2 1Department of Central Laboratory, Fuda Cancer Hospital, Jinan University School of Medicine, Guangzhou, Guangdong, China; 2Fuda Cancer Institute, Guangzhou, Guangdong, China; 3Hank Bioengineering Co., Ltd, Shenzhen, China Abstract: In the present study, we aimed to compare the clinical outcome of autogeneic and allogeneic natural killer (NK cells immunotherapy for the treatment of recurrent breast cancer. Between July 2016 and February 2017, 36 patients who met the enrollment criteria were randomly assigned to two groups: autogeneic NK cells immunotherapy group (group I, n=18 and allogeneic NK cells immunotherapy group (group II, n=18. The clinical efficacy, quality of life, immune function, circulating tumor cell (CTC level, and other related indicators were evaluated. We found that allogeneic NK cells immunotherapy has better clinical efficacy than autogeneic therapy. Moreover, allogeneic NK cells therapy improves the quality of life, reduces the number of CTCs, reduces carcinoembryonic antigen and cancer antigen 15-3 (CA15-3 expression, and significantly enhances immune function. To our knowledge, this is the first clinical trial to compare the clinical outcome of autogeneic and allogeneic NK cells immunotherapy for recurrent breast cancer. Keywords: clinical outcome, autogeneic, allogeneic, natural killer cells, recurrent breast cancer

  9. Xenogeneic chimera-Generated by blastocyst complementation-As a potential unlimited source of recipient-tailored organs.

    Science.gov (United States)

    Oldani, Graziano; Peloso, Andrea; Lacotte, Stéphanie; Meier, Raphael; Toso, Christian

    2017-07-01

    Blastocyst complementation refers to the injection of cells into a blastocyst. The technology allows for the creation of chimeric animals, which have the potential to be used as an unlimited source of organ donors. Pluripotent stem cells could be generated from a patient in need of a transplantation and injected into a large animal blastocyst (potentially of a pig), leading to the creation of organ(s) allowing immunosuppression-free transplantation. Various chimera combinations have already been generated, but one of the most recent steps leads to the creation of human-pig chimeras, which could be studied at an embryo stage. Although still far from clinical reality, the potential application is almost unlimited. The present review illustrates the historical steps of intra- and interspecific blastocyst complementation in rodents and large animals, specifically looking at its potential for generation of organ grafts. We also speculate on how it could change transplant indications, on its economic impact, and on the linked ethical concerns. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Incomplete development of the spleen and the deformity in the chimeras between asplenic mutant (Dominant hemimelia) and normal mice.

    Science.gov (United States)

    Suto, J; Wakayama, T; Imamura, K; Goto, S; Fukuta, K

    1995-08-01

    The semidominant gene Dh (Dominant hemimelia) induces skeletal and visceral abnormalities of various degrees and failure of the spleen in mice. The homozygous individual (Dh/Dh) seems to be lethal. The present experiment was designed to investigate the ability Dh cells to form a spleen and the genesis of the hind limb malformations by Dh/Dh and Dh/+ cells in chimeric mice. The Dh/Dh and Dh/+ embryos were produced in the F2 progeny of a cross between inbred strains of Dh/+ and DDD mice. They were aggregated with C3H/He or C57BL/6 embryos to make chimeras. Identification of Dh/Dh or Dh/+ embryos was carried out by Pep-3, and chimerism was analyzed by Gpi-1. Of 25 chimeras carrying the Dh gene, four mice formed a small spleen, two mice had a vestigial spleen, and the others no spleen. The tissues of the incompletely developed spleens were normal histologically and Dh cells were involved in the tissues of the spleen. In the chimeric mice, hindlimb malformation by the Dh gene was reduced in severity and the lethality of the homozygote (Dh/Dh) was rescued.

  11. SCHEMA computational design of virus capsid chimeras: calibrating how genome packaging, protection, and transduction correlate with calculated structural disruption.

    Science.gov (United States)

    Ho, Michelle L; Adler, Benjamin A; Torre, Michael L; Silberg, Jonathan J; Suh, Junghae

    2013-12-20

    Adeno-associated virus (AAV) recombination can result in chimeric capsid protein subunits whose ability to assemble into an oligomeric capsid, package a genome, and transduce cells depends on the inheritance of sequence from different AAV parents. To develop quantitative design principles for guiding site-directed recombination of AAV capsids, we have examined how capsid structural perturbations predicted by the SCHEMA algorithm correlate with experimental measurements of disruption in seventeen chimeric capsid proteins. In our small chimera population, created by recombining AAV serotypes 2 and 4, we found that protection of viral genomes and cellular transduction were inversely related to calculated disruption of the capsid structure. Interestingly, however, we did not observe a correlation between genome packaging and calculated structural disruption; a majority of the chimeric capsid proteins formed at least partially assembled capsids and more than half packaged genomes, including those with the highest SCHEMA disruption. These results suggest that the sequence space accessed by recombination of divergent AAV serotypes is rich in capsid chimeras that assemble into 60-mer capsids and package viral genomes. Overall, the SCHEMA algorithm may be useful for delineating quantitative design principles to guide the creation of libraries enriched in genome-protecting virus nanoparticles that can effectively transduce cells. Such improvements to the virus design process may help advance not only gene therapy applications but also other bionanotechnologies dependent upon the development of viruses with new sequences and functions.

  12. Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion

    Science.gov (United States)

    Henry, David A; Carless, Paul A; Moxey, Annette J; O’Connell, Dianne; Stokes, Barrie J; Fergusson, Dean A; Ker, Katharine

    2014-01-01

    a non-significant increase in the risk of myocardial infarction (RR 1.11 95% CI 0.82, 1.50). Most of the data contributing to this added risk came from a single study - the BART trial (2008). Authors’ conclusions Anti-fibrinolytic drugs provide worthwhile reductions in blood loss and the receipt of allogeneic red cell transfusion. Aprotinin appears to be slightly more effective than the lysine analogues in reducing blood loss and the receipt of blood transfusion. However, head to head comparisons show a lower risk of death with lysine analogues when compared with aprotinin. The lysine analogues are effective in reducing blood loss during and after surgery, and appear to be free of serious adverse effects. PMID:21412876

  13. Nonmyeloablative and reduced-intensity conditioning for allogeneic hematopoietic stem cell transplantation: a clinical review.

    Science.gov (United States)

    Pollack, Seth M; O'Connor, Thomas P; Hashash, Jana; Tabbara, Imad A

    2009-12-01

    Allogeneic hematopoietic stem cell transplantation provides many patients, with hematological and malignant diseases, hope of remission and in some cases cure. Because the toxicities of this approach are severe, its use has been limited to younger healthier patients. Nonmyeloablative and reduced intensity conditioning regimens depend more on donor cellular immune effects and less on the cytotoxic effects of the conditioning regimen to eradicate the underlying disease. This approach is based on the induction of host tolerance to donor cells followed by the administration of scheduled donor T-lymphocytes infusions. Accumulated clinical data have been encouraging, and prospective studies are underway to compare this approach to conventional myeloablative allogeneic stem cell transplantation with regard to outcome, durability of responses, effects on the immune system, and the consequences of late complications such as chronic graft-versus-host disease.

  14. Fungemia due to Rhodotorula mucilaginosa after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Mori, T; Nakamura, Y; Kato, J; Sugita, K; Murata, M; Kamei, K; Okamoto, S

    2012-02-01

    Rhodotorula species have been increasingly recognized as emerging pathogens, particularly in immunocompromised patients. We herein report on a patient with myelodysplastic syndrome who developed fungemia due to Rhodotorula mucilaginosa after allogeneic hematopoietic stem cell transplantation (HSCT) from an unrelated donor. He developed severe acute graft-versus-host disease requiring high-dose steroids, and had serially been administered fluconazole and micafungin for the prophylaxis of fungal infection. Although several cases of Rhodotorula infection after HSCT have been reported, all of them were recipients of autologous HSCT, not allogeneic HSCT. A review of all the reported cases of Rhodotorula infection after HSCT revealed that all patients had received fluconazole or echinocandins before the onset of infection. The findings suggest that Rhodotorula species could be causative yeasts, particularly in patients receiving fluconazole or echinocandins, both of which are inactive against the species. © 2011 John Wiley & Sons A/S.

  15. Immune responses to an encapsulated allogeneic islet β-cell line in diabetic NOD mice

    International Nuclear Information System (INIS)

    Black, Sasha P.; Constantinidis, Ioannis; Cui, Hong; Tucker-Burden, Carol; Weber, Collin J.; Safley, Susan A.

    2006-01-01

    Our goal is to develop effective islet grafts for treating type 1 diabetes. Since human islets are scarce, we evaluated the efficacy of a microencapsulated insulin-secreting conditionally transformed allogeneic β-cell line (βTC-tet) in non-obese diabetic mice treated with tetracycline to inhibit cell growth. Relatively low serum levels of tetracycline controlled proliferation of βTC-tet cells without inhibiting effective control of hyperglycemia in recipients. There was no significant host cellular reaction to the allografts or host cell adherence to microcapsules, and host cytokine levels were similar to those of sham-operated controls. We conclude that encapsulated allogeneic β-cell lines may be clinically relevant, because they effectively restore euglycemia and do not elicit a strong cellular immune response following transplantation. To our knowledge, this is First extensive characterization of the kinetics of host cellular and cytokine responses to an encapsulated islet cell line in an animal model of type 1 diabetes

  16. Lichen striatus occurring after allogenic peripheral blood stem cell transplantation in an adult with aplastic anemia.

    Science.gov (United States)

    Mun, Je-Ho; Park, Hyun-Je; Kim, Hoon-Soo; Kim, Su-Han; Ko, Hyun-Chang; Kim, Byung-Soo; Kim, Moon-Bum

    2012-02-01

    Lichens striatus (LS) is an acquired, self-limiting inflammatory dermatosis that follows the lines of Blaschko. The etiology of the eruption is unknown, but several theories have been proposed with focus on environmental factors, viral infection, cutaneous injury, hypersensitivity, and genetic predisposition. We describe a 19-year-old woman who developed a unilateral linear eruption 17 months after allogenic peripheral blood stem cell transplantation. Histopathology revealed features, which were consistent with LS. To the best of our knowledge, our patient is the first case describing the appearance of LS occurring after allogenic stem cell transplantation. We speculate that this condition represents an unusual form of localized, chronic graft-versus-host disease.

  17. Lung function after allogeneic bone marrow transplantation for leukaemia or lymphoma

    DEFF Research Database (Denmark)

    Nysom, K; Holm, K; Hesse, B

    1996-01-01

    Longitudinal data were analysed on the lung function of 25 of 29 survivors of childhood leukaemia or lymphoma, who had been conditioned with cyclophosphamide and total body irradiation before allogeneic bone marrow transplantation, to test whether children are particularly vulnerable to pulmonary...... damage after transplantation. None developed chronic graft-versus-host disease. Transfer factor and lung volumes were reduced immediately after bone marrow transplantation, but increased during the following years. However, at the last follow up, 4-13 years (median 8) after transplantation, patients had...... to their age at bone marrow transplantation. In conclusion, patients had subclinical restrictive pulmonary disease at a median of eight years after total body irradiation and allogeneic bone marrow transplantation....

  18. Allogeneic bone marrow transplantation in adults after fractionated body irradiation and high dose cyclophosphamide

    International Nuclear Information System (INIS)

    Brinch, L.; Evensen, S.A.; Albrechtsen, D.; Egeland, T.; Solheim, B.G.; Rollag, H.; Naalsund, A.; Jacobsen, A.B.

    1991-01-01

    The authors present short and long-term results of allogeneic bone marrow transplantation after hyper-fractionated total body irradiation and high dose cyclophosphamide in ten patients treated for leukaemia during th period 1985-89. Three patients died from complications connected to the transplantation, while seven are living free from leukaemia 18 to 59 months after transplantation. Two patients need treatment for chronic graft versus host disease. Allogeneic bone marrow transplantation is expensive and risky. Close cooperation between clinicians and laboratory specialists is essential. The treatment increases long term survival and probably cures certain patients with leukaemia. Some of the patients will need treatment for chronic graft versus host disease and other late sequelae. 19 refs., 2 tabs

  19. Numbers and dispersion of repopulating hematopoietic cell clones in radiation chimeras as functions of injected cell dose

    International Nuclear Information System (INIS)

    Micklem, H.S.; Lennon, J.E.; Ansell, J.D.; Gray, R.A.

    1987-01-01

    Lethally irradiated mice were repopulated with low (10(5)), medium (10(6)) or high (10(7)) doses of congenic bone marrow cells. Marrow donors were heterozygous for the X-chromosome-encoded allozyme marker phosphoglycerate kinase (PGK-1). A second allozyme marker, phosphoglucose isomerase (GPI-1), distinguished between donor and radioresistant host cells. Use of these markers allowed the numbers and dispersion of repopulating hematopoietic clones to be estimated by binomial statistics. The number of major repopulating clones was related to the injected cell dose in a linear fashion, the inferred frequency of clonogenic cells in donor bone marrow being about 1:40,000. In high-dose recipients, the clones grew locally, with little or no dispersion between bones. Low-dose recipients, in contrast, carried widely dispersed clones; these tended to become reduced in number with increasing time after repopulation. Most of the (few) bone marrow clones present in low-dose recipients were also present in the thymus. In contrast, only about 10% of bone marrow clones in high-dose recipients were substantially represented in the thymus at any one time--about 16 clones in each lobe

  20. Rational management of hunting and gathering: An aristotelian entelechy or a chimera?

    Directory of Open Access Journals (Sweden)

    Juan Mario Vargas Yáñez

    2018-01-01

    Full Text Available Rational management of hunting and gathering: An Aristotelian entelechy or a chimera? Since the dawn of time, consumption of animal protein has been crucially important to the evolution of humans. Cooperative hunting is an Evolutionarily Stable Strategy from the time when Palaeolithic hunters specialized in the pursuit of large animals. The entire process involves making decisions related to game management, some of which are still used by contemporary hunter-gatherers. In these societies, which still practice subsistence hunting, the composition of their diets and the exploitation techniques employed are explained by the theoretical underpinnings contained in the Optimal Foraging Theory (OFT. In order to test this theory, we have taken into account four decisions involving the adoption of different management strategies by hunter-gatherers: I what to eat, II where and how to look for food, III the most appropriate size and composition of the group of hunter-gatherers and IV the most efficient guidelines for the handling and distribution of prey. The OFT has been tested several times, and in a high percentage of cases studied, its predictions fit observations made in various hunter-gatherer societies. This means that maximizing catch yields in the short term is their main concern, rather than behaving as ‘cautious predators’ or passively selecting prey according to their size, accessibility and abundance. Such behaviour does not contradict the possibility that hunter-gatherers can act as conservationists, but discards the idea that this is the main focus of their way of life. There is no doubt that indigenous peoples have a wide knowledge of the environment, but it is unclear this knowledge is used to maintain a balance with nature or to be more efficient hunters. It more likely that the presence of sustainable hunting of game is due to low hunting pressure in areas where animal prey is abundant, and is thus an epiphenomenon rather than a

  1. Long-term survival of transplanted allogeneic cells engineered to express a T cell chemorepellent.

    Science.gov (United States)

    Papeta, Natalia; Chen, Tao; Vianello, Fabrizio; Gererty, Lyle; Malik, Ashish; Mok, Ying-Ting; Tharp, William G; Bagley, Jessamyn; Zhao, Guiling; Stevceva, Liljana; Yoon, Victor; Sykes, Megan; Sachs, David; Iacomini, John; Poznansky, Mark C

    2007-01-27

    Alloantigen specific T cells have been shown to be required for allograft rejection. The chemokine, stromal cell derived factor-1 (SDF-1) at high concentration, has been shown to act as a T-cell chemorepellent and abrogate T-cell infiltration into a site of antigen challenge in vivo via a mechanism termed fugetaxis or chemorepulsion. We postulated that this mechanism could be exploited therapeutically and that allogeneic cells engineered to express a chemorepellent protein would not be rejected. Allogeneic murine insulinoma beta-TC3 cells and primary islets from BALB/C mice were engineered to constitutively secrete differential levels of SDF-1 and transplanted into allogeneic diabetic C57BL/6 mice. Rejection was defined as the permanent return of hyperglycemia and was correlated with the level of T-cell infiltration. The migratory response of T-cells to SDF-1 was also analyzed by transwell migration assay and time-lapse videomicroscopy. The cytotoxicity of cytotoxic T cell (CTLs) against beta-TC3 cells expressing high levels of SDF-1 was measured in standard and modified chromium-release assays in order to determine the effect of CTL migration on killing efficacy. Control animals rejected allogeneic cells and remained diabetic. In contrast, high level SDF-1 production by transplanted cells resulted in increased survival of the allograft and a significant reduction in blood glucose levels and T-cell infiltration into the transplanted tissue. This is the first demonstration of a novel approach that exploits T-cell chemorepulsion to induce site specific immune isolation and thereby overcomes allograft rejection without the use of systemic immunosuppression.

  2. Lichen Striatus Occurring after Allogenic Peripheral Blood Stem Cell Transplantation in an Adult with Aplastic Anemia

    OpenAIRE

    Mun, Je-Ho; Park, Hyun-Je; Kim, Hoon-Soo; Kim, Su-Han; Ko, Hyun-Chang; Kim, Byung-Soo; Kim, Moon-Bum

    2012-01-01

    Lichens striatus (LS) is an acquired, self-limiting inflammatory dermatosis that follows the lines of Blaschko. The etiology of the eruption is unknown, but several theories have been proposed with focus on environmental factors, viral infection, cutaneous injury, hypersensitivity, and genetic predisposition. We describe a 19-year-old woman who developed a unilateral linear eruption 17 months after allogenic peripheral blood stem cell transplantation. Histopathology revealed features, which w...

  3. Activated allogeneic NK cells preferentially kill poor prognosis B-cell chronic lymphocytic leukemia cells

    Directory of Open Access Journals (Sweden)

    Diego Sanchez-Martinez

    2016-10-01

    Full Text Available Mutational status of TP53 together with expression of wild type (wt IGHV represents the most widely accepted biomarkers, establishing a very poor prognosis in B-cell chronic lymphocytic leukemia (B-CLL patients. Adoptive cell therapy using allogeneic HLA mismatched Natural Killer (NK cells has emerged as an effective and safe alternative in the treatment of acute myeloid and lymphoid leukemias that do not respond to traditional therapies. We have described that allogeneic activated NK cells eliminate hematological cancer cell lines with multidrug resistance acquired by mutations in the apoptotic machinery. This effect depends on the activation protocol, being B-lymphoblastoid cell lines (LCLs the most effective stimulus to activate NK cells. Here we have further analyzed the molecular determinants involved in allogeneic NK cell recognition and elimination of B-CLL cells, including the expression of ligands of the main NK cell activating receptors (NKG2D and NCRs and HLA mismatch. We present preliminary data suggesting that B-CLL susceptibility significantly correlates with HLA mismatch between NK cell donor and B-CLL patient. Moreover, we show that the sensitivity of B-CLL cells to NK cells depends on the prognosis based on TP53 and IGHV mutational status. Cells from patients with worse prognosis (mutated TP53 and wt IGHV are the most susceptible to activated NK cells. Hence, B-CLL prognosis may predict the efficacy of allogenic activated NK cells and, thus, NK cell transfer represents a good alternative to treat poor prognosis B-CLL patients who present a very short life expectancy due to lack of effective treatments.□

  4. Activated Allogeneic NK Cells Preferentially Kill Poor Prognosis B-Cell Chronic Lymphocytic Leukemia Cells.

    Science.gov (United States)

    Sánchez-Martínez, Diego; Lanuza, Pilar M; Gómez, Natalia; Muntasell, Aura; Cisneros, Elisa; Moraru, Manuela; Azaceta, Gemma; Anel, Alberto; Martínez-Lostao, Luis; Villalba, Martin; Palomera, Luis; Vilches, Carlos; García Marco, José A; Pardo, Julián

    2016-01-01

    Mutational status of TP53 together with expression of wild-type (wt) IGHV represents the most widely accepted biomarkers, establishing a very poor prognosis in B-cell chronic lymphocytic leukemia (B-CLL) patients. Adoptive cell therapy using allogeneic HLA-mismatched Natural killer (NK) cells has emerged as an effective and safe alternative in the treatment of acute myeloid and lymphoid leukemias that do not respond to traditional therapies. We have described that allogeneic activated NK cells eliminate hematological cancer cell lines with multidrug resistance acquired by mutations in the apoptotic machinery. This effect depends on the activation protocol, being B-lymphoblastoid cell lines (LCLs) the most effective stimulus to activate NK cells. Here, we have further analyzed the molecular determinants involved in allogeneic NK cell recognition and elimination of B-CLL cells, including the expression of ligands of the main NK cell-activating receptors (NKG2D and NCRs) and HLA mismatch. We present preliminary data suggesting that B-CLL susceptibility significantly correlates with HLA mismatch between NK cell donor and B-CLL patient. Moreover, we show that the sensitivity of B-CLL cells to NK cells depends on the prognosis based on TP53 and IGHV mutational status. Cells from patients with worse prognosis (mutated TP53 and wt IGHV ) are the most susceptible to activated NK cells. Hence, B-CLL prognosis may predict the efficacy of allogenic activated NK cells, and, thus, NK cell transfer represents a good alternative to treat poor prognosis B-CLL patients who present a very short life expectancy due to lack of effective treatments.

  5. A novel cancer vaccine strategy based on HLA-A*0201 matched allogeneic plasmacytoid dendritic cells.

    Directory of Open Access Journals (Sweden)

    Caroline Aspord

    Full Text Available BACKGROUND: The development of effective cancer vaccines still remains a challenge. Despite the crucial role of plasmacytoid dendritic cells (pDCs in anti-tumor responses, their therapeutic potential has not yet been worked out. We explored the relevance of HLA-A*0201 matched allogeneic pDCs as vectors for immunotherapy. METHODS AND FINDINGS: Stimulation of PBMC from HLA-A*0201(+ donors by HLA-A*0201 matched allogeneic pDCs pulsed with tumor-derived peptides triggered high levels of antigen-specific and functional cytotoxic T cell responses (up to 98% tetramer(+ CD8 T cells. The pDC vaccine demonstrated strong anti-tumor therapeutic in vivo efficacy as shown by the inhibition of tumor growth in a humanized mouse model. It also elicited highly functional tumor-specific T cells ex-vivo from PBMC and TIL of stage I-IV melanoma patients. Responses against MelA, GP100, tyrosinase and MAGE-3 antigens reached tetramer levels up to 62%, 24%, 85% and 4.3% respectively. pDC vaccine-primed T cells specifically killed patients' own autologous melanoma tumor cells. This semi-allogeneic pDC vaccine was more effective than conventional myeloid DC-based vaccines. Furthermore, the pDC vaccine design endows it with a strong potential for clinical application in cancer treatment. CONCLUSIONS: These findings highlight HLA-A*0201 matched allogeneic pDCs as potent inducers of tumor immunity and provide a promising immunotherapeutic strategy to fight cancer.

  6. Informed consent: cultural and religious issues associated with the use of allogeneic and xenogeneic mesh products.

    Science.gov (United States)

    Jenkins, Eric D; Yip, Michael; Melman, Lora; Frisella, Margaret M; Matthews, Brent D

    2010-04-01

    Our aim was to investigate the views of major religions and cultural groups regarding the use of allogeneic and xenogeneic mesh for soft tissue repair. We contacted representatives from Judaism, Islam, Buddhism, Hinduism, Scientology, and Christianity (Baptists, Methodists, Seventh-Day Adventists, Catholics, Lutherans, Church of Jesus Christ of Latter-Day Saints, Evangelical, and Jehovah's Witnesses). We also contacted American Vegan and People for the Ethical Treatment of Animals (PETA). Standardized questionnaires were distributed to the religious and cultural authorities. Questions solicited views on the consumption of beef and pork products and the acceptability of human-, bovine-, or porcine-derived acellular grafts. Dietary restrictions among Jews and Muslims do not translate to tissue implantation restriction. Approximately 50% of Seventh-day Adventists and 40% of Buddhists practice vegetarianism, which may translate into a refusal of the use of xenogeneic tissue. Some Hindus categorically prohibit the use of human tissue and animal products; others allow the donation and receipt of human organs and tissues. PETA is opposed to all uses of animals, but not to human acellular grafts or organ transplantation. Some vegans prefer allogeneic to xenogeneic tissue. Allogeneic and xenogeneic acellular grafts are acceptable among Scientologists, Baptists, Lutherans, Evangelicals, and Catholics. Methodists, Jehovah's Witnesses, and The Church of Jesus Christ of Latter-Day Saints leave the decision up to the individual. Knowledge of religious and cultural preferences regarding biologic mesh assists the surgeon in obtaining a culturally sensitive informed consent for procedures involving acellular allogeneic or xenogeneic grafts. Copyright (c) 2010 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

  7. Aerobic exercise capacity at long-term follow-up after paediatric allogeneic haematopoietic SCT

    DEFF Research Database (Denmark)

    Mathiesen, S; Uhlving, H H; Buchvald, F

    2014-01-01

    Peak oxygen uptake (VO2peak), a measure of aerobic exercise capacity, predicts mortality and morbidity in healthy and diseased individuals. Our aim was to determine VO2peak years after paediatric allogeneic haematopoietic SCT (HSCT) and to identify associations with baseline patient and donor...... type or GvHD were found. Although causes for reduced VO2peak may be multiple, our findings stress the need to focus on physical activity post HSCT to prevent lifestyle diseases and improve quality of life....

  8. Clinical and Surgical Strategies for Avoiding or Reducing Allogeneic Blood Transfusions

    OpenAIRE

    dos Santos, Antonio Alceu; Baumgratz, Jose Francisco; Vila, Jose Henrique Andrade; Castro, Rodrigo Moreira; Bezerra, Rodrigo Freire

    2016-01-01

    Blood transfusions have still been used as a standard therapy to treat severe anemia. Current evidences point to both excessive allogeneic blood consumption and decreased donations, which result in reduced stocks in blood banks. Several studies have increasingly suggested a more restrictive transfusion practice for blood products. Currently, a number of autologous blood conservation protocols in surgeries have been noted. We report a case of severe anemia with 2.9 g/dL hemoglobin, which was s...

  9. Correlation and Agreement of Handheld Spirometry with Laboratory Spirometry in Allogeneic Hematopoietic Cell Transplant Recipients.

    Science.gov (United States)

    Cheng, Guang-Shing; Campbell, Angela P; Xie, Hu; Stednick, Zach; Callais, Cheryl; Leisenring, Wendy M; Englund, Janet A; Chien, Jason W; Boeckh, Michael

    2016-05-01

    Early detection of subclinical lung function decline may help identify allogeneic hematopoietic cell transplant (HCT) recipients who are at increased risk for late noninfectious pulmonary complications, including bronchiolitis obliterans syndrome. We evaluated the use of handheld spirometry in this population. Allogeneic HCT recipients enrolled in a single-center observational trial performed weekly spirometry with a handheld spirometer for 1 year after transplantation. Participants performed pulmonary function tests in an outpatient laboratory setting at 3 time points: before transplantation, at day 80 after transplantation, and at 1 year after transplantation. Correlation between the 2 methods was assessed by Pearson and Spearman correlations; agreement was assessed using Bland-Altman plots. A total of 437 subjects had evaluable pulmonary function tests. Correlation for forced expiratory volume in 1 second (FEV1) was r = .954 (P spirometry correlated well with laboratory spirometry after allogeneic HCT and may be useful for self-monitoring of patients for early identification of airflow obstruction. Copyright © 2016 American Society for Blood and Marrow Transplantation. All rights reserved.

  10. Allogeneic fetal stem cell transplantation to child with psychomotor retardation: A case report

    Directory of Open Access Journals (Sweden)

    Dajić Katerina

    2016-01-01

    Full Text Available Introduction. The consequences of autologous and allogeneic stem cell transplantation (stem cells of hematopoiesis, applied in adults and children suffering from leukemia or some other malignant disease, are well-known and sufficiently recognizable in pediatric clinical practice regardless of the indication for the treatment. However, the efficacy of fetal stem cell transplantation is unrecognizable when the indications are psychomotor retardation and epilepsy. Case Outline. With the exception of neurological psychiatric problems, a boy aged 9.5 years was in good general health before transplantation with allogeneic fetal stem cells. The main aim of allogeneic fetal stem cell transplantation was treatment of psychomotor retardation and epilepsy. After 13 months of treatment, he was admitted to hospital in a very serious, life-threatening condition due to sepsis and severe pleuropneumonia. The humoral immunity in the boy was adequate, unlike cellular immunity. The immune imbalance in terms of predominance of T-suppressor lymphocytes contributes to delayed and late development of sepsis and severe pleuropneumonia. The boy still shows the same severity of psychomotor retardation, dyslalia, epilepsy, strabismus and amblyopia. Conclusion. Implementation of fetal stem cell therapy for unconfirmed indications abuses the therapeutic approach, harms patients, misleads parents, and brings financial harm to the healthcare system of any country, including Serbia.

  11. Humanized mouse model for assessing the human immune response to xenogeneic and allogeneic decellularized biomaterials.

    Science.gov (United States)

    Wang, Raymond M; Johnson, Todd D; He, Jingjin; Rong, Zhili; Wong, Michelle; Nigam, Vishal; Behfar, Atta; Xu, Yang; Christman, Karen L

    2017-06-01

    Current assessment of biomaterial biocompatibility is typically implemented in wild type rodent models. Unfortunately, different characteristics of the immune systems in rodents versus humans limit the capability of these models to mimic the human immune response to naturally derived biomaterials. Here we investigated the utility of humanized mice as an improved model for testing naturally derived biomaterials. Two injectable hydrogels derived from decellularized porcine or human cadaveric myocardium were compared. Three days and one week after subcutaneous injection, the hydrogels were analyzed for early and mid-phase immune responses, respectively. Immune cells in the humanized mouse model, particularly T-helper cells, responded distinctly between the xenogeneic and allogeneic biomaterials. The allogeneic extracellular matrix derived hydrogels elicited significantly reduced total, human specific, and CD4 + T-helper cell infiltration in humanized mice compared to xenogeneic extracellular matrix hydrogels, which was not recapitulated in wild type mice. T-helper cells, in response to the allogeneic hydrogel material, were also less polarized towards a pro-remodeling Th2 phenotype compared to xenogeneic extracellular matrix hydrogels in humanized mice. In both models, both biomaterials induced the infiltration of macrophages polarized towards a M2 phenotype and T-helper cells polarized towards a Th2 phenotype. In conclusion, these studies showed the importance of testing naturally derived biomaterials in immune competent animals and the potential of utilizing this humanized mouse model for further studying human immune cell responses to biomaterials in an in vivo environment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Allogeneic stem cell transplantation for advanced acute promyelocytic leukemia in the ATRA and ATO era

    Science.gov (United States)

    Ramadan, Safaa M.; Di Veroli, Ambra; Camboni, Agnese; Breccia, Massimo; Iori, Anna Paola; Aversa, Franco; Cupelli, Luca; Papayannidis, Cristina; Bacigalupo, Andrea; Arcese, William; Lo-Coco, Francesco

    2012-01-01

    The role of allogeneic stem cell transplant in advanced acute promyelocytic leukemia patients who received standard first- and second-line therapy is still unknown. We report the outcome of 31 acute promyelocytic leukemia patients (median age 39 years) who underwent allogeneic transplant in second remission (n=15) or beyond (n=16). Sixteen patients were real-time polymerase chain reaction positive and 15 negative for PML/RARA pre-transplant. The 4-year overall survival was 62% and 31% for patients transplanted in second remission and beyond, respectively (P=0.05), and 64% and 27% for patients with pre-transplant negative and positive real-time polymerase chain reaction, respectively (P=0.03). The 4-year cumulative incidence of relapse was 32% and 44% for patients transplanted in second remission and beyond, respectively (P=0.37), and 30% and 47% for patients transplanted with negative and positive real-time polymerase chain reaction, respectively (P=0.30). Transplant-related mortality was 19.6%. In conclusion, allogeneic transplant is effective in advanced acute promyelocytic leukemia in the all-trans-retinoic acid and arsenic trioxide era, and should be considered once relapse is diagnosed. PMID:22689684

  13. TNFRSF14 aberrations in follicular lymphoma increase clinically significant allogeneic T-cell responses.

    Science.gov (United States)

    Kotsiou, Eleni; Okosun, Jessica; Besley, Caroline; Iqbal, Sameena; Matthews, Janet; Fitzgibbon, Jude; Gribben, John G; Davies, Jeffrey K

    2016-07-07

    Donor T-cell immune responses can eradicate lymphomas after allogeneic hematopoietic stem cell transplantation (AHSCT), but can also damage healthy tissues resulting in harmful graft-versus-host disease (GVHD). Next-generation sequencing has recently identified many new genetic lesions in follicular lymphoma (FL). One such gene, tumor necrosis factor receptor superfamily 14 (TNFRSF14), abnormal in 40% of FL patients, encodes the herpes virus entry mediator (HVEM) which limits T-cell activation via ligation of the B- and T-lymphocyte attenuator. As lymphoma B cells can act as antigen-presenting cells, we hypothesized that TNFRSF14 aberrations that reduce HVEM expression could alter the capacity of FL B cells to stimulate allogeneic T-cell responses and impact the outcome of AHSCT. In an in vitro model of alloreactivity, human lymphoma B cells with TNFRSF14 aberrations had reduced HVEM expression and greater alloantigen-presenting capacity than wild-type lymphoma B cells. The increased immune-stimulatory capacity of lymphoma B cells with TNFRSF14 aberrations had clinical relevance, associating with higher incidence of acute GVHD in patients undergoing AHSCT. FL patients with TNFRSF14 aberrations may benefit from more aggressive immunosuppression to reduce harmful GVHD after transplantation. Importantly, this study is the first to demonstrate the impact of an acquired genetic lesion on the capacity of tumor cells to stimulate allogeneic T-cell immune responses which may have wider consequences for adoptive immunotherapy strategies. © 2016 by The American Society of Hematology.

  14. Allogeneic BMT and patient eligibility based on psychosocial criteria: a survey of BMT professionals.

    Science.gov (United States)

    Foster, L W; McLellan, L J; Rybicki, L A; Dabney, J; Welsh, E; Bolwell, B J

    2006-01-01

    BMT professionals were compared regarding their willingness to proceed with allogeneic BMT given select psychosocial issues. A questionnaire was sent to 660 physician members of ASBMT, 92 social work members of BMT Special Interest Group, Association of Oncology Social Work, and 626 nurse members of BMT Special Interest Group, Oncology Nursing Society; 597 responded with a response rate of 43.5%. Items included background information, followed by 17 case vignettes; each represented a different psychosocial issue to which respondents indicated whether or not they would recommend proceeding with allogeneic BMT. In every vignette, at least 10% of respondents indicated they would not proceed. In six vignettes, at least 64% indicated do not proceed: suicidal ideation (86.8%), uses addictive illicit drugs (81.7%), history of noncompliance (80.5%), no lay caregiver (69.3%), alcoholic (64.8%), and mild dementia/Alzheimer's (64.4%). In 10 vignettes, at least 73% indicated proceed. On four vignettes, professional subgroups differed in their recommendation on whether or not to proceed with allogeneic BMT. Qualitative data suggest that this decision is contingent on the perceived acuity, severity, and currency of the psychosocial issue, patient ability to comply with treatment given the issue, and its manageability as a risk factor for treatment related vulnerability and outcomes.

  15. Feasibility of combination allogeneic stem cell therapy for spinal cord injury: a case report

    Directory of Open Access Journals (Sweden)

    Ichim Thomas E

    2010-11-01

    Full Text Available Abstract Cellular therapy for spinal cord injury (SCI is overviewed focusing on bone marrow mononuclear cells, olfactory ensheathing cells, and mesenchymal stem cells. A case is made for the possibility of combining cell types, as well as for allogeneic use. We report the case of 29 year old male who suffered a crush fracture of the L1 vertebral body, lacking lower sensorimotor function, being a score A on the ASIA scale. Stem cell therapy comprised of intrathecal administration of allogeneic umbilical cord blood ex-vivo expanded CD34 and umbilical cord matrix MSC was performed 5 months, 8 months, and 14 months after injury. Cell administration was well tolerated with no adverse effects observed. Neuropathic pain subsided from intermittent 10/10 to once a week 3/10 VAS. Recovery of muscle, bowel and sexual function was noted, along with a decrease in ASIA score to "D". This case supports further investigation into allogeneic-based stem cell therapies for SCI.

  16. Cytogenetic conversion following allogeneic bone marrow transplantation for advanced chronic myelogenous leukemia

    International Nuclear Information System (INIS)

    McGlave, P.B.; Miller, W.J.; Hurd, D.D.; Arthur, D.C.; Kim, T.

    1981-01-01

    We performed a pilot study to test the effectiveness of allogeneic bone marrow transplantation in the treatment of chronic myelogenous leukemia. Five patients in the advanced stages of chronic myelogenous leukemia (four in blast crisis, one in accelerated phase) with abnormal chromosomes underwent matched-sibling allogeneic bone marrow transplantation after preparation with busulfan, vincristine, cyclophosphamide, and fractionated total body irradiation. Engraftment and conversion to normal chromosome patterns after transplantation occurred in all five patients. None of the patients reverted to an abnormal chromosome pattern or demonstrated clinical or hematologic evidence of recurrent disease during the course of this study; however, longest survival from transplant was 248 days. Allogeneic bone marrow transplantation can eradicate the abnormal clone even in far advanced chronic myelogenous leukemia and can provide normal hematopoiesis. We suggest that clinical complications of chemotherapeutic toxicity and infection were responsible for the short survival in this group of patients, and that these complications could be decreased by performing transplantation in the chronic phase or early accelerated phase of the disease

  17. Reversal of acute (''malignant'') myelosclerosis by allogeneic bone marrow transplantation

    International Nuclear Information System (INIS)

    Wolf, J.L.; Spruce, W.E.; Bearman, R.M.; Forman, S.J.; Scott, E.P.; Fahey, J. L.; Farbstein, M.J.; Rappaport, H.; Blume, K.G.

    1982-01-01

    A 28-yr-old woman with acute malignant myelosclerosis received, as primary treatment, ablative chemotherapy and total body radiation therapy followed by bone marrow transplantation from her histocompatible brother. The patient is now well more than 15 mo after bone marrow transplantation, with normal peripheral blood counts, a normal bone marrow, no evidence of graft-versus-host disease, and is on no therapy. In light of the poor results obtained with conventional chemotherapy in this disease, bone marrow transplantation may represent the treatment of choice for patients who have an appropriate donor

  18. Brucella-Salmonella lipopolysaccharide chimeras are less permeable to hydrophobic probes and more sensitive to cationic peptides and EDTA than are their native Brucella sp. counterparts.

    Science.gov (United States)

    Freer, E; Moreno, E; Moriyón, I; Pizarro-Cerdá, J; Weintraub, A; Gorvel, J P

    1996-01-01

    A rough (R) Brucella abortus 45/20 mutant was more sensitive to the bactericidal activity of polymyxin B and lactoferricin B than was its smooth (S) counterpart but considerably more resistant than Salmonella montevideo. The outer membrane (OM) and isolated lipopolysaccharide (LPS) of S. montevideo showed a higher affinity for these cationic peptides than did the corresponding B. abortus OM and LPS. We took advantage of the moderate sensitivity of R B. abortus to cationic peptides to construct live R B. abortus-S-LPS chimeras to test the activities of polymyxin B, lactoferricin B, and EDTA. Homogeneous and abundant peripheral distribution of the heterologous S-LPS was observed on the surface of the chimeras, and this coating had no effect on the viability or morphology of the cells. When the heterologous LPS corresponded to the less sensitive bacterium S B. abortus S19, the chimeras were more resistant to cationic peptides; in contrast, when the S-LPS was from the more sensitive bacterium S. montevideo, the chimeras were more susceptible to the action of peptides and EDTA. A direct correlation between the amount of heterologous S-LPS on the surface of chimeric Brucella cells and peptide sensitivity was observed. Whereas the damage produced by polymyxin B in S. montevideo and B. abortus-S. montevideo S-LPS chimeras was manifested mainly as OM blebbing and inner membrane rolling, lactoferricin B caused inner membrane detachment, vacuolization, and the formation of internal electron-dense granules in these cells. Native S and R B. abortus strains were permeable to the hydrophobic probe N-phenyl-1-naphthylamine (NPN). In contrast, only reduced amounts of NPN partitioned into the OMs of the S. montevideo and B. abortus-S. montevideo S-LPS chimeras. Following peptide exposure, accelerated NPN uptake similar to that observed for S. montevideo was detected for the B. abortus-S. montevideo LPS chimeras. The partition of NPN into native or EDTA-, polymyxin B-, or

  19. Brucella-Salmonella lipopolysaccharide chimeras are less permeable to hydrophobic probes and more sensitive to cationic peptides and EDTA than are their native Brucella sp. counterparts.

    Science.gov (United States)

    Freer, E; Moreno, E; Moriyón, I; Pizarro-Cerdá, J; Weintraub, A; Gorvel, J P

    1996-10-01

    A rough (R) Brucella abortus 45/20 mutant was more sensitive to the bactericidal activity of polymyxin B and lactoferricin B than was its smooth (S) counterpart but considerably more resistant than Salmonella montevideo. The outer membrane (OM) and isolated lipopolysaccharide (LPS) of S. montevideo showed a higher affinity for these cationic peptides than did the corresponding B. abortus OM and LPS. We took advantage of the moderate sensitivity of R B. abortus to cationic peptides to construct live R B. abortus-S-LPS chimeras to test the activities of polymyxin B, lactoferricin B, and EDTA. Homogeneous and abundant peripheral distribution of the heterologous S-LPS was observed on the surface of the chimeras, and this coating had no effect on the viability or morphology of the cells. When the heterologous LPS corresponded to the less sensitive bacterium S B. abortus S19, the chimeras were more resistant to cationic peptides; in contrast, when the S-LPS was from the more sensitive bacterium S. montevideo, the chimeras were more susceptible to the action of peptides and EDTA. A direct correlation between the amount of heterologous S-LPS on the surface of chimeric Brucella cells and peptide sensitivity was observed. Whereas the damage produced by polymyxin B in S. montevideo and B. abortus-S. montevideo S-LPS chimeras was manifested mainly as OM blebbing and inner membrane rolling, lactoferricin B caused inner membrane detachment, vacuolization, and the formation of internal electron-dense granules in these cells. Native S and R B. abortus strains were permeable to the hydrophobic probe N-phenyl-1-naphthylamine (NPN). In contrast, only reduced amounts of NPN partitioned into the OMs of the S. montevideo and B. abortus-S. montevideo S-LPS chimeras. Following peptide exposure, accelerated NPN uptake similar to that observed for S. montevideo was detected for the B. abortus-S. montevideo LPS chimeras. The partition of NPN into native or EDTA-, polymyxin B-, or

  20. Insights into the Activity and Substrate Binding of Xylella fastidiosa Polygalacturonase by Modification of a Unique QMK Amino Acid Motif Using Protein Chimeras.

    Science.gov (United States)

    Warren, Jeremy G; Lincoln, James E; Kirkpatrick, Bruce C

    2015-01-01

    Polygalacturonases (EC 3.2.1.15) catalyze the random hydrolysis of 1, 4-alpha-D-galactosiduronic linkages in pectate and other galacturonans. Xylella fastidiosa possesses a single polygalacturonase gene, pglA (PD1485), and X. fastidiosa mutants deficient in the production of polygalacturonase are non-pathogenic and show a compromised ability to systemically infect grapevines. These results suggested that grapevines expressing sufficient amounts of an inhibitor of X. fastidiosa polygalacturonase might be protected from disease. Previous work in our laboratory and others have tried without success to produce soluble active X. fastidiosa polygalacturonase for use in inhibition assays. In this study, we created two enzymatically active X. fastidiosa / A. vitis polygalacturonase chimeras, AX1A and AX2A to explore the functionality of X. fastidiosa polygalacturonase in vitro. The AX1A chimera was constructed to specifically test if recombinant chimeric protein, produced in Escherichia coli, is soluble and if the X. fastidiosa polygalacturonase catalytic amino acids are able to hydrolyze polygalacturonic acid. The AX2A chimera was constructed to evaluate the ability of a unique QMK motif of X. fastidiosa polygalacturonase, most polygalacturonases have a R(I/L)K motif, to bind to and allow the hydrolysis of polygalacturonic acid. Furthermore, the AX2A chimera was also used to explore what effect modification of the QMK motif of X. fastidiosa polygalacturonase to a conserved RIK motif has on enzymatic activity. These experiments showed that both the AX1A and AX2A polygalacturonase chimeras were soluble and able to hydrolyze the polygalacturonic acid substrate. Additionally, the modification of the QMK motif to the conserved RIK motif eliminated hydrolytic activity, suggesting that the QMK motif is important for the activity of X. fastidiosa polygalacturonase. This result suggests X. fastidiosa polygalacturonase may preferentially hydrolyze a different pectic substrate or

  1. Systemic Administration of Allogeneic Mesenchymal Stem Cells Does Not Halt Osteoporotic Bone Loss in Ovariectomized Rats.

    Directory of Open Access Journals (Sweden)

    Shuo Huang

    Full Text Available Mesenchymal stem cells (MSCs have innate ability to self-renew and immunosuppressive functions, and differentiate into various cell types. They have become a promising cell source for treating many diseases, particular for bone regeneration. Osteoporosis is a common metabolic bone disorder with elevated systemic inflammation which in turn triggers enhanced bone loss. We hypothesize that systemic infusion of MSCs may suppress the elevated inflammation in the osteoporotic subjects and slow down bone loss. The current project was to address the following two questions: (1 Will a single dose systemic administration of allogenic MSCs have any effect on osteoporotic bone loss? (2 Will multiple administration of allogenic MSCs from single or multiple donors have similar effect on osteoporotic bone loss? 18 ovariectomized (OVX rats were assigned into 3 groups: the PBS control group, MSCs group 1 (receiving 2x106 GFP-MSCs at Day 10, 46, 91 from the same donor following OVX and MSCs group 2 (receiving 2x106 GFP-MSCs from three different donors at Day 10, 46, 91. Examinations included Micro-CT, serum analysis, mechanical testing, immunofluorescence staining and bone histomorphometry analysis. Results showed that BV/TV at Day 90, 135, BMD of TV and trabecular number at Day 135 in the PBS group were significantly higher than those in the MSCs group 2, whereas trabecular spacing at Day 90, 135 was significantly smaller than that in MSCs group 2. Mechanical testing data didn't show significant difference among the three groups. In addition, the ELISA assay showed that level of Rantes in serum in MSCs group 2 was significantly higher than that of the PBS group, whereas IL-6 and IL-10 were significantly lower than those of the PBS group. Bone histomorphometry analysis showed that Oc.S/BS and Oc.N/BS in the PBS group were significant lower than those in MSCs group 2; Ob.S/BS and Ob.N/BS did not show significant difference among the three groups. The current study

  2. Development of PET Imaging to Visualize Activated Macrophages Accumulated in the Transplanted iPSc-Derived Cardiac Myocytes of Allogeneic Origin for Detecting the Immune Rejection of Allogeneic Cell Transplants in Mice.

    Directory of Open Access Journals (Sweden)

    Noriyuki Kashiyama

    Full Text Available Allogeneic transplantation (Tx of induced pluripotent stem cells (iPSCs is a promising tissue regeneration therapy. However, this inevitably induces macrophage-mediated immune response against the graft, limiting its therapeutic efficacy. Monitoring the magnitude of the immune response using imaging tools would be useful for prolonging graft survival and increasing the therapy longevity. Minimally invasive quantitative detection of activated macrophages by medical imaging technologies such as positron emission tomography (PET imaging targets translocator protein (TSPO, which is highly expressed on mitochondrial membrane, especially in activated macrophage. N,N-diethyl-2-[4-(2-fluoroethoxy phenyl]-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-acetamide (DPA-714 is known as a TSPO ligand used in clinical settings. We herein hypothesized that immune rejection of the transplanted iPSC-derived cardiomyocytes (iPSC-CMs of allogeneic origin may be quantitated using 18F-DPA-714-PET imaging study. iPSC-CM cell-sheets of C57BL/6 mice origin were transplanted on the surface of the left ventricle (LV of C57BL/6 mice as a syngeneic cell-transplant model (syngeneic Tx group, or Balb/c mice as an allogeneic model (allogeneic Tx group. 18F-DPA-714-PET was used to determine the uptake ratio, calculated as the maximum standardized uptake value in the anterior and septal wall of the LV. The uptake ratio was significantly higher in the allogeneic Tx group than in the syngeneic group or the sham group at days 7 and day 10 after the cell transplantation. In addition, the immunochemistry showed significant presence of CD68 and CD3-positive cells at day 7 and 10 in the transplanted graft of the allogeneic Tx group. The expression of TSPO, CD68, IL-1 beta, and MCP-1 was significantly higher in the allogeneic Tx group than in the syngeneic Tx and the sham groups at day 7. The 18F-DPA-714-PET imaging study enabled quantitative visualization of the macrophages-mediated immune

  3. Isolated Extramedullary Relapse of Acute Leukemia after Allogeneic Stem Cell Transplantation: Different Kinetics and Better Prognosis than Systemic Relapse.

    Science.gov (United States)

    Shem-Tov, Noga; Saraceni, Francesco; Danylesko, Ivetta; Shouval, Roni; Yerushalmi, Ronit; Nagler, Arnon; Shimoni, Avichai

    2017-07-01

    Allogeneic stem cell transplantation (SCT) is curative treatment in patients with acute leukemia and myelodysplastic syndrome. However, recurrent disease is the major cause of treatment failure. Isolated extramedullary relapse (iEMR) after SCT is relatively rare and not well characterized. We performed a retrospective analysis of 566 consecutive patients with acute myeloid leukemia (n = 446) and acute lymphoblastic leukemia (ALL; n = 120) after SCT to study the incidence, risk factors, treatment options, and outcome of iEMR. The 5-year cumulative incidence of bone marrow relapse (BMR) and iEMR was 41.0% and 5.8%, respectively. iEMR occurred significantly later than BMR at 10 and 4 months, respectively (P BMR but did not protect against iEMR. Most patients with iEMR received systemic treatment combined with local radiation and donor lymphocyte infusions when feasible. The 3-year survival after relapse was 8.5% and 30.1% after BMR and iEMR, respectively (P = .002). Patients with a first iEMR continued to have recurrent EMRs, and only a minority progressed to BMR. Second iEMR was also common after first BMR and associated with longer survival than second BMR. iEMR is more frequent in patients with ALL and prior extramedullary disease. It occurs later than BMR and more commonly in patients with chronic GVHD, suggesting less effective graft-versus-leukemia effect in extramedullary sites. Second iEMR is common after a first iEMR but also after a first BMR. Long-term survival is feasible with aggressive treatment. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  4. Structure of 10Be and 16C nuclei via break-up reactions studied with the 4π Chimera array

    Science.gov (United States)

    Dell'Aquila, D.; Acosta, L.; Amorini, F.; Andolina, R.; Auditore, L.; Berceanu, I.; Cardella, G.; Chatterjiee, M. B.; De Filippo, E.; Francalanza, L.; Gnoffo, B.; Grzeszczuk, A.; Lanzalone, G.; Lombardo, I.; Martorana, N.; Minniti, T.; Pagano, A.; Pagano, E. V.; Papa, M.; Pirrone, S.; Politi, G.; Pop, A.; Porto, F.; Quattrocchi, L.; Rizzo, F.; Rosato, E.; Russotto, P.; Trifirò, A.; Trimarchi, M.; Verde, G.; Vigilante, M.

    2018-01-01

    The study of cluster states in neutron-rich Be and C isotopes is a subject of interest in Nuclear Physics. These states should be characterized by high deformation where α-clusters are bounded by valence neutrons. We performed a spectroscopic study of 10Be and 16C isotopes via projectile break-up reactions, by using radioactive beams produced at the INFN-LNS FRIBs facility and the Chimera 4π array. The possible evidence of a new 10Be state at 13.5 MeV excitation energy was found in the 6He+4He disintegration channel. The spectroscopy of 16C was studied via the 6He+10Be break-up channel; in this case we found the indication of a possible new state at about 20.6 MeV.

  5. Simulation of unsteady flows through stator and rotor blades of a gas turbine using the Chimera method

    Science.gov (United States)

    Nakamura, S.; Scott, J. N.

    1993-01-01

    A two-dimensional model to solve compressible Navier-Stokes equations for the flow through stator and rotor blades of a turbine is developed. The flow domains for the stator and rotor blades are coupled by the Chimera method that makes grid generation easy and enhances accuracy because the area of the grid that have high turning of grid lines or high skewness can be eliminated from the computational domain after the grids are generated. The results of flow computations show various important features of unsteady flows including the acoustic waves interacting with boundary layers, Karman vortex shedding from the trailing edge of the stator blades, pulsating incoming flow to a rotor blade from passing stator blades, and flow separation from both suction and pressure sides of the rotor blades.

  6. New type of chimera and mutual synchronization of spatiotemporal structures in two coupled ensembles of nonlocally interacting chaotic maps

    Science.gov (United States)

    Bukh, Andrei; Rybalova, Elena; Semenova, Nadezhda; Strelkova, Galina; Anishchenko, Vadim

    2017-11-01

    We study numerically the dynamics of a network made of two coupled one-dimensional ensembles of discrete-time systems. The first ensemble is represented by a ring of nonlocally coupled Henon maps and the second one by a ring of nonlocally coupled Lozi maps. We find that the network of coupled ensembles can realize all the spatio-temporal structures which are observed both in the Henon map ensemble and in the Lozi map ensemble while uncoupled. Moreover, we reveal a new type of spatiotemporal structure, a solitary state chimera, in the considered network. We also establish and describe the effect of mutual synchronization of various complex spatiotemporal patterns in the system of two coupled ensembles of Henon and Lozi maps.

  7. Radiobiological researches on Dianthus caryophyllus L. carnation chimeras; Recherches radiobiologiques sur des chimeres d'oeillet Dianthus caryophyllus L.

    Energy Technology Data Exchange (ETDEWEB)

    Pereau-Leroy, Pierre

    1975-04-12

    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 [French] Une etude radiobiologique de chimeres periclinales d'oeillet est effectuee en soumettant au rayonnement gamma du cobalt 60, sous differentes conditions de doses et debits de dose, des plantes entieres et des boutures a des stades physiologiques differents. Les effets des traitements sont observes au cours de la culture des plantes traitees et par l'examen microscopique de coupes des meristemes irradies. La destruction de cellules meristematiques, dans des proportions variables avec les modalites d'irradiation, provoque des modifications de structure des chimeres dont les plus frequentes sont la formation de tiges genetiquement homogenes a partir des differents genotypes existants dans la plante irradiee. Le traitement aux radiations ionisantes constitue donc une methode pratique de detection des chimeres periclinales qui, a l'image de ce qui se passe pour l'oeillet, sont tres repandues chez les plantes cultivees a propagation vegetative. Mais, comme il existe generalement plus de deux ensembles cellulaires meristematiques independants, cette methode ne permet pas, a elle seule, de definir la repartition des differents genotypes dans ces ensembles; elle doit alors etre completee par des etudes genetiques ou des marquages cellulaires tels que des mutations chlorophylliennes ou de genomes. Ainsi la structure de deux varietes d'oeillet a fleurs oranges, qui produisent, apres irradiation, des fleurs rouges et des fleurs jaunes, a ete determinee grace a l'obtention, par traitement a la colchicine, de cytochimeres 4 - 2 - 2 et 2 - 4 - 4. Les tiges a fleurs jaunes, produites par

  8. Allogeneic amniotic membrane-derived mesenchymal stromal cell transplantation in a porcine model of chronic myocardial ischemia

    Directory of Open Access Journals (Sweden)

    Kimura M

    2012-01-01

    Full Text Available Introduction. Amniotic membrane contains a multipotential stem cell population and is expected to possess the machinery to regulate immunological reactions. We investigated the safety and efficacy of allogeneic amniotic membrane-derived mesenchymal stromal cell (AMSC transplantation in a porcine model of chronic myocardial ischemia as a preclinical trial. Methods. Porcine AMSCs were isolated from amniotic membranes obtained by cesarean section just before delivery and were cultured to increase their numbers before transplantation. Chronic myocardial ischemia was induced by implantation of an ameroid constrictor around the left circumflex coronary artery. Four weeks after ischemia induction, nine swine were assigned to undergo either allogeneic AMSC transplantation or normal saline injection. Functional analysis was performed by echocardiography, and histological examinations were carried out by immunohistochemistry 4 weeks after AMSC transplantation. Results. Echocardiography demonstrated that left ventricular ejection fraction was significantly improved and left ventricular dilatation was well attenuated 4 weeks after AMSC transplantation. Histological assessment showed a significant reduction in percentage of fibrosis in the AMSC transplantation group. Injected allogeneic green fluorescent protein (GFP-expressing AMSCs were identified in the immunocompetent host heart without the use of any immunosuppressants 4 weeks after transplantation. Immunohistochemistry revealed that GFP colocalized with cardiac troponin T and cardiac troponin I. Conclusions. We have demonstrated that allogeneic AMSC transplantation produced histological and functional improvement in the impaired myocardium in a porcine model of chronic myocardial ischemia. The transplanted allogeneic AMSCs survived without the use of any immunosuppressants and gained cardiac phenotype through either their transdifferentiation or cell fusion.

  9. The influence of specific binding of collagen-silk chimeras to silk biomaterials on hMSC behavior.

    Science.gov (United States)

    An, Bo; DesRochers, Teresa M; Qin, Guokui; Xia, Xiaoxia; Thiagarajan, Geetha; Brodsky, Barbara; Kaplan, David L

    2013-01-01

    Collagen-like proteins in the bacteria Streptococcus pyogenes adopt a triple-helix structure with a thermal stability similar to that of animal collagens, can be expressed in high yield in Escherichia coli and can be easily modified through molecular biology techniques. However, potential applications for such recombinant collagens are limited by their lack of higher order structure to achieve the physical properties needed for most biomaterials. To overcome this problem, the S. pyogenes collagen domain was fused to a repetitive Bombyx mori silk consensus sequence, as a strategy to direct specific non-covalent binding onto solid silk materials whose superior stability, mechanical and material properties have been previously established. This approach resulted in the successful binding of these new collagen-silk chimeric proteins to silk films and porous scaffolds, and the binding affinity could be controlled by varying the number of repeats in the silk sequence. To explore the potential of collagen-silk chimera for regulating biological activity, integrin (Int) and fibronectin (Fn) binding sequences from mammalian collagens were introduced into the bacterial collagen domain. The attachment of bioactive collagen-silk chimeras to solid silk biomaterials promoted hMSC spreading and proliferation substantially in comparison to the controls. The ability to combine the biomaterial features of silk with the biological activities of collagen allowed more rapid cell interactions with silk-based biomaterials, improved regulation of stem cell growth and differentiation, as well as the formation of artificial extracellular matrices useful for tissue engineering applications. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Dhananjay R Namjoshi

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

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

    Science.gov (United States)

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

    2016-01-01

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

  12. Chimeras of Bet v 1 and Api g 1 reveal heterogeneous IgE responses in patients with birch pollen allergy.

    Science.gov (United States)

    Gepp, Barbara; Lengger, Nina; Bublin, Merima; Hemmer, Wolfgang; Breiteneder, Heimo; Radauer, Christian

    2014-07-01

    Characterization of IgE-binding epitopes of allergens and determination of their patient-specific relevance is crucial for the diagnosis and treatment of allergy. We sought to assess the contribution of specific surface areas of the major birch pollen allergen Bet v 1.0101 to binding IgE of individual patients. Four distinct areas of Bet v 1 representing in total 81% of its surface were grafted onto the scaffold of its homolog, Api g 1.0101, to yield the chimeras Api-Bet-1 to Api-Bet-4. The chimeras were expressed in Escherichia coli and purified. IgE binding of 64 sera from Bet v 1-sensitized subjects with birch pollen allergy was determined by using direct ELISA. Specificity was assessed by means of inhibition ELISA. rApi g 1.0101, Api-Bet-1, Api-Bet-2, Api-Bet-3, and Api-Bet-4 bound IgE from 44%, 89%, 80%, 78%, and 48% of the patients, respectively. By comparing the amount of IgE binding to the chimeras and to rApi g 1.0101, 81%, 70%, 75%, and 45% of the patients showed significantly enhanced IgE binding to Api-Bet-1, Api-Bet-2, Api-Bet-3, and Api-Bet-4, respectively. The minority (8%) of the sera revealed enhanced IgE binding exclusively to a single chimera, whereas 31% showed increased IgE binding to all 4 chimeras compared with rApi g 1.0101. The chimeras inhibited up to 70% of IgE binding to rBet v 1.0101, confirming the specific IgE recognition of the grafted regions. The Bet v 1-specific IgE response is polyclonal, and epitopes are spread across the entire Bet v 1 surface. Furthermore, the IgE recognition profile of Bet v 1 is highly patient specific. Copyright © 2014 The Authors. Published by Mosby, Inc. All rights reserved.

  13. Similar effect of autologous and allogeneic cell therapy for ischemic heart disease : Systematic review and meta-analysis of large animal studies

    NARCIS (Netherlands)

    Jansen of Lorkeers, Sanne J.; Eding, Joep Egbert Coenraad; Vesterinen, Hanna Mikaela; van der Spoel, Tycho Ids Gijsbert; Sena, Emily Shamiso; Duckers, Henricus Johannes; Doevendans, Pieter Adrianus; Macleod, Malcolm Robert; Chamuleau, Steven Anton Jozef

    2015-01-01

    Rationale: In regenerative therapy for ischemic heart disease, use of both autologous and allogeneic stem cells has been investigated. Autologous cell can be applied without immunosuppression, but availability is restricted, and cells have been exposed to risk factors and aging. Allogeneic cell

  14. Progression and CSF Inflammation after Eradication of Oligoclonal Bands in an MS Patient Treated with Allogeneic Hematopoietic Cell Transplantation for Follicular Lymphoma

    DEFF Research Database (Denmark)

    Braendstrup, P; Langkilde, Annika; Schreiber, K

    2012-01-01

    Allogeneic hematopoietic cell transplantation (allo-HCT) has been proposed as treatment for multiple sclerosis (MS) and other autoimmune diseases.......Allogeneic hematopoietic cell transplantation (allo-HCT) has been proposed as treatment for multiple sclerosis (MS) and other autoimmune diseases....

  15. Do autologous blood transfusion systems reduce allogeneic blood transfusion in total knee arthroplasty?

    Science.gov (United States)

    Pawaskar, Aditya; Salunke, Abhijeet Ashok; Kekatpure, Aashay; Chen, Yongsheng; Nambi, G I; Tan, Junhao; Sonawane, Dhiraj; Pathak, Subodhkumar

    2017-09-01

    To study whether autologus blood transfusion systems reduce the requirement of allogneic blood transfusion in patients undergoing total knee arthroplasty. A comprehensive search of the published literature with PubMed, Scopus and Science direct database was performed. The following search terms were used: (total knee replacement) OR (total knee arthroplasty) OR (TKA) AND (blood transfusion) OR (autologous transfusion) OR (autologous transfusion system). Using search syntax, a total of 748 search results were obtained (79 from PubMed, 586 from Science direct and 83 from Scopus). Twenty-one randomized control trials were included for this meta-analysis. The allogenic transfusion rate in autologus blood transfusion (study) group was significantly lower than the control group (28.4 and 53.5 %, respectively) (p value 0.0001, Relative risk: 0.5). The median units of allogenic blood transfused in study control group and control group were 0.1 (0.1-3.0) and 1.3 (0.3-2.6), respectively. The median hospital stay in study group was 9 (6.7-15.6) days and control group was 8.7 (6.6-16.7) days. The median cost incurred for blood transfusion per patient in study and control groups was 175 (85.7-260) and 254.7 (235-300) euros, respectively. This meta-analysis demonstrates that the use of auto-transfusion systems is a cost-effective method to reduce the need for and quantity of allogenic transfusion in elective total knee arthroplasty. Level I.

  16. Electron beam irradiation to the allogeneic, xenogenic and synthetic bone materials

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Soung Min; Park, Min Woo; Jeong, Hyun Oh [School of Dentistry Seoul National University, Seoul (Korea, Republic of); and others

    2013-07-01

    For the development of the biocompatible bony regeneration materials, allogenic, xenogenic and synthetic bone were irradiated by electron beam to change the basic components and structures. For the efficient electron beam irradiating condition of these allogenic, xenogenic and artificial bone substitutes, the optimal electron beam energy and their individual dose were established, to maximize the bony regeneration capacity. Commercial products of four allogenic bones, such as Accell (ISOTIS OrthogBiologics Co., USA), Allotis (Korea Bone Bank Co., Korea), Oragraft (LifeNet Co., USA), and Orthoblast (Integra Orthobiologics Inc., USA), six xenogenic bones, such as BBP (OscoTec Co., Korea), Bio-cera (OscoTec Co., Korea), Bio-oss (Geistlich Pharma AG, Switzerland), Indu-cera (OscoTec Co., Korea), OCS-B (Nibec Co., Korea), and OCS-H (Nibec Co., Korea), and six synthetic bones, such as BMP (Couellmedi Co., Korea), BoneMedik (Meta Biomed Co., Korea), Bone plus (Megagen Co., Korea), MBCP (Biomatlante Co., France), Osteon (Genoss Co., Korea), and Osteogen (Impladent LTD., USA), were used. We used 1.0 and 2.0 MeV superconduction accelerator, and/or microtrone with different individual 60, 120 kGy irradiation dose. Different dose irradiated specimens were divided 6 portions each, so total 360 groups were prepared. 4 portions were analyzed each by elementary analysis using FE-SEM (Field Emission Scanning Microscopy) and another 2 portions were grafted to the calvarial defect of Sprague-Dawley rat, following histologic, immunohistochemical analysis and TEM study were processed at the 8th and 16th weeks, in vivo. This work was supported by the National Research Foundation of Korea(NRF) grant funded by the Korea government(MEST)

  17. Frozen allogeneic human epidermal cultured sheets for the cure of complicated leg ulcers.

    Science.gov (United States)

    Bolívar-Flores, Y J; Kuri-Harcuch, W

    1999-08-01

    Skin ulcers due to venous stasis or diabetes are common among the elderly and are difficult to treat. Repeated applications of cell-based products have been reported to result in cure or improvement of leg ulcers of small size in a fraction of patients. To examine the effects of frozen human allogeneic epidermal cultures for the treatment of acute and chronic ulcers. We treated a series of 10 consecutive patients with leg ulcers of different etiology and duration with frozen human allogeneic epidermal cultures stored frozen and thawed for 5-10 minutes at room temperature before application. Three patients had ulcers with exposed Achilles or extensor tendon. The ulcers treated were as large as 160 cm2 in area and of up to 20-years' duration. After preliminary preparation of the wounds by debridement to remove necrotic tissue and application of silver sulfadiazine to control infection, thawed cultures were applied biweekly from 2 to 15 times depending on the size and complexity of the ulcer. All ulcers healed, including those with tendon exposure. After the first few applications, granulation tissue formed in the ulcer bed and on exposed tendons, and epidermal healing took place through proliferation and migration of cells from the margins of the wound. The time required for complete healing ranged from 1 to 31 weeks after the first application. The use of frozen human allogeneic epidermal cultures is a safe and effective treatment for venous or diabetic ulcers, even those with tendon exposure. It seems possible that any leg ulcer will be amenable to successful treatment by this method.

  18. Reduced use of allogeneic platelets through high-yield perioperative autologous plateletpheresis and reinfusion.

    Science.gov (United States)

    Alberts, Melissa; Bandarenko, Nicholas; Gaca, Jeffrey; Lockhart, Evelyn; Milano, Carmelo; Alexander, Stanlin; Linder, Dean; Lombard, Frederick W; Welsby, Ian J

    2014-05-01

    Intraoperative autologous platelet (PLT) collection as part of a multimodal blood conservation program carries a Class IIa recommendation from the Societies of Thoracic Surgeons and Cardiovascular Anesthesiologists, but achieving a suitable PLT yield limits its application. A novel, autologous, intraoperative, high-yield plateletpheresis collection program was established and retrospectively analyzed to identify potential improvements over previously reported plateletpheresis protocols. Targeting complex cardiothoracic surgery patients without recent anti-PLT agents, thrombocytopenia, or severe anemia, the program aimed to achieve a PLT yield of at least one standard apheresis unit (3.0 × 10(11) ) within 60 to 90 minutes and using an automated plateletpheresis device (Trima, Terumo BCT). Anesthetized and invasively monitored patients underwent plateletpheresis via a large-bore, indwelling central line placed for the surgery. Collection-related data for quality control purposes and subsequent PLT transfusion requirements were analyzed and reported. Forty-two patients donated autologous PLTs between 2011 and 2012. PLT yield was 4.5 (3.9-5.0) × 10(11) , which significantly exceeds previously reported yields, and procedure duration was 53.2 (48.4-57.9) minutes. As anticipated, postcollection PLT count decreased from 268 (242-293) × 10(9) to 182 (163-201) × 10(9) /L; hypocalcemia was minimized by infusion of 1 g of CaCl2 . Autologous PLT yield was inversely correlated with allogeneic PLT use, and avoidance of allogeneic PLT transfusion was increased when the autologous yield was the equivalent of 2 or more apheresis units. High-yield, intraoperative autologous PLT collection is achievable using an automated plateletpheresis device. Initial experience shows a reduction in reliance on allogeneic PLTs for complex cardiothoracic surgery. © 2013 American Association of Blood Banks.

  19. Application of human amniotic mesenchymal cells as an allogeneic transplantation cell source in bone regenerative therapy

    International Nuclear Information System (INIS)

    Tsuno, Hiroaki; Yoshida, Toshiko; Nogami, Makiko; Koike, Chika; Okabe, Motonori; Noto, Zenko; Arai, Naoya; Noguchi, Makoto; Nikaido, Toshio

    2012-01-01

    Autogenous mesenchymal stem cells (MSCs) have therapeutic applications in bone regenerative therapy due to their pluripotency. However, the ability of MSCs to proliferate and differentiate varies between donors. Furthermore, alternative sources of MSCs are required for patients with contraindications to autogenous cell therapy. The aim of this study was to evaluate the potential of mesenchymal cells from the human amniotic membrane (HAM) as a source of cells for allogeneic transplantation in bone regenerative therapy. Cells that retained a proliferative capacity of more than 50 population doubling level were distinguished from other HAM cells as HAMα cells and induced to osteogenic status—their in vivo osteogenesis was subsequently investigated in rats. It was found that HAMα cells were spindle shaped and were positive for MSC markers and negative for hematopoietic stem cell markers. Alkaline phosphatase activity and calcium deposition increased with osteogenic status of HAMα cells. The expression of osteocalcin mRNA was increased in HAMα cells cultured on calcium phosphate scaffolds. Moreover, xenografted HAMα cells remained viable and produced extracellular matrix for several weeks. Thus, this study suggests that human amniotic mesenchymal cells possess osteogenic differentiation potential and could be applied to allogeneic transplantation in bone regenerative therapy. - Highlights: ► Human amniotic mesenchymal cells include cells (HAMα cells) that have the properties of MSCs. ► HAMα cells have excellent osteogenic differentiation potential. ► Osteogenic differentiation ability of HAMα was amplified by calcium phosphate scaffolds. ► HAMα cells can be applicable to allogeneic cell transplantation in bone regenerative therapy.

  20. Application of human amniotic mesenchymal cells as an allogeneic transplantation cell source in bone regenerative therapy

    Energy Technology Data Exchange (ETDEWEB)

    Tsuno, Hiroaki [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Yoshida, Toshiko [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Nogami, Makiko [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Department of Orthopedic Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Koike, Chika; Okabe, Motonori [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Noto, Zenko [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Arai, Naoya; Noguchi, Makoto [Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Nikaido, Toshio, E-mail: tnikaido@med.u-toyama.ac.jp [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan)

    2012-12-01

    Autogenous mesenchymal stem cells (MSCs) have therapeutic applications in bone regenerative therapy due to their pluripotency. However, the ability of MSCs to proliferate and differentiate varies between donors. Furthermore, alternative sources of MSCs are required for patients with contraindications to autogenous cell therapy. The aim of this study was to evaluate the potential of mesenchymal cells from the human amniotic membrane (HAM) as a source of cells for allogeneic transplantation in bone regenerative therapy. Cells that retained a proliferative capacity of more than 50 population doubling level were distinguished from other HAM cells as HAM{alpha} cells and induced to osteogenic status-their in vivo osteogenesis was subsequently investigated in rats. It was found that HAM{alpha} cells were spindle shaped and were positive for MSC markers and negative for hematopoietic stem cell markers. Alkaline phosphatase activity and calcium deposition increased with osteogenic status of HAM{alpha} cells. The expression of osteocalcin mRNA was increased in HAM{alpha} cells cultured on calcium phosphate scaffolds. Moreover, xenografted HAM{alpha} cells remained viable and produced extracellular matrix for several weeks. Thus, this study suggests that human amniotic mesenchymal cells possess osteogenic differentiation potential and could be applied to allogeneic transplantation in bone regenerative therapy. - Highlights: Black-Right-Pointing-Pointer Human amniotic mesenchymal cells include cells (HAM{alpha} cells) that have the properties of MSCs. Black-Right-Pointing-Pointer HAM{alpha} cells have excellent osteogenic differentiation potential. Black-Right-Pointing-Pointer Osteogenic differentiation ability of HAM{alpha} was amplified by calcium phosphate scaffolds. Black-Right-Pointing-Pointer HAM{alpha} cells can be applicable to allogeneic cell transplantation in bone regenerative therapy.