Controlling transition probability from matter-wave soliton to chaos

For a Bose-Einstein condensate loaded into a weak traveling optical superlattice it is demonstrated that under a stochastic initial set and in a given parameter region the solitonic chaos appears with a certain probability. Effects of the lattice depths and wave vectors on the chaos probability are investigated analytically and numerically, and different chaotic regions associated with different chaos probabilities are found. The results suggest a feasible method for eliminating or strengthening chaos by modulating the moving superlattice experimentally.Comment: 4 pages, 2 figure

Discrete chaotic states of a Bose-Einstein condensate

We find the different spatial chaos in a one-dimensional attractive Bose-Einstein condensate interacting with a Gaussian-like laser barrier and perturbed by a weak optical lattice. For the low laser barrier the chaotic regions of parameters are demonstrated and the chaotic and regular states are illustrated numerically. In the high barrier case, the bounded perturbed solutions which describe a set of discrete chaotic states are constructed for the discrete barrier heights and magic numbers of condensed atoms. The chaotic density profiles are exhibited numerically for the lowest quantum number, and the analytically bounded but numerically unbounded Gaussian-like configurations are confirmed. It is shown that the chaotic wave packets can be controlled experimentally by adjusting the laser barrier potential.Comment: 7 pages, 5 figure

Tolerance-Inducing Strategies in Islet Transplantation

Allogeneic islet transplantation is a promising approach for restoring normoglycemia in type 1 diabetic patients. Current use of immunosuppressive therapies for management of islet transplant recipients can be counterintuitive to islet function and can lead to complications in the long term. The induction of donor-specific tolerance eliminates the dependency on immunosuppression and allows recipients to retain responses to foreign antigens. The mechanisms by which tolerance is achieved involve the deletion of donor-reactive T cells, induction of T-cell anergy, immune deviation, and generation of regulatory T cells. This review will outline the various methods used for inducing donor-specific tolerance in islet transplantation and will highlight the previously unforeseen potential of tissue stromal cells in promoting islet engraftment

Interferon-γ induced expression of MHC antigens facilitates identification of donor cells in chimeric transplant recipients

After whole organ transplantation, donor bone marrow-derived cells migrate out of the graft into the recipient, leading to establishment of chimerism, which is the first step towards the subsequent induction of donor-specific tolerance. In routine immunohistochemical staining, monoclonal antibodies specific for heterotopic MHC alleles are used to identify donor and recipient cells. However, it is difficult to detect these cells using this technique in long-term allograft recipients who have a persistently low donor cell population (microchimerism). Because Interferon-gamma (IFN-γ) is known to induce expression of MHC class I and class II cell surface molecules, we used this cytokine 12-48 h before sacrifice, to facilitate the identification of donor and recipient cells in the tissues of animals transplanted with either liver (B10 → C3H) or bone marrow (LEW → BN). In long-term allograft recipients, the use of IFN-γ for as briefly as 12 h prior to sacrifice, results in marked upregulation of class I and class II antigens, leading to easy identification of ubiquitously distributed low numbers of donor cells. © 1994

Costimulatory molecule-deficient dendritic cell progenitors (MHC class II⁺, CD80(dim), CD86^-) prolong cardiac allograft survival in nonimmunosuppressed recipients

We have shown previously that granulocyte-macrophage colony-stimulating factor-stimulated mouse bone marrow-derived MHC class II+ dendritic cell (DC) progenitors that are deficient in cell surface expression of the costimulatory molecules B7-1 (CD8O) and B7-2 (CD86) can induce alloantigen- specific T-cell anergy in vitro. To test the in vivo relevance of these findings, 2 x 106 B10 (H2(b)) mouse bone marrow-derived DC progenitors (NLDC 145+, MHC class II+, B7-1(dim), B7-2(-/dim)) that induced T-cell hyporesponsiveness in vitro were injected systemically into normal C3H (H2(k)) recipients. Seven days later, the mice received heterotopic heart transplants from B10 donors. No immunosuppressive treatment was given. Median graft survival time was prolonged significantly from 9.5 to 22 days. Median graft survival time was also increased, although to a lesser extent (16.5 days), in mice that received third-party (BALB/c; H2(d)) DC progenitors. Ex vivo analysis of host T-cell responses to donor and third-party alloantigens 7 days after the injection of DC progenitors (the time of heart transplant) revealed minimal anti-donor mixed leukocyte reaction and cytotoxic T lymphocyte reactivity. These responses were reduced substantially compared with those of spleen cells from animals pretreated with 'mature' granulocyte- macrophage colony-stimulating factor + interleukin-4-stimulated DC (MHC class II(bright), B7-1+, B7-2(bright)), many of which rejected their heart grafts in an accelerated fashion. Among the injected donor MHC class II+ DC progenitors that migrated to recipient secondary lymphoid tissue were cells that appeared to have up-regulated cell surface B7-1 and B7-2 molecule expression. This observation may explain, at least in part, the temporary or unstable nature of the hyporesponsiveness induced by the DC progenitors in nonimmunosuppressed recipients

Increased apoptosis of immunoreactive host cells and augmented donor leukocyte chimerism, not sustained inhibition of B7 molecule expression are associated with prolonged cardiac allograft survival in mice preconditioned with immature donor dendritic cells plus anti-CD40L mAb

Background. We previously reported the association among donor leukocyte chimerism, apoptosis of presumedly IL-2-deficient graft-infiltrating host cells, and the spontaneous donor-specific tolerance induced by liver but not heart allografts in mice. Survival of the rejection-prone heart allografts in the same strain combination is modestly prolonged by the pretransplant infusion of immature, costimulatory molecule-(CM) deficient donor dendritic cells (DC), an effect that is markedly potentiated by concomitant CM blockade with anti-CD40L (CD154) monoclonal antibody (mAb). We investigated whether the long survival of the heart allografts in the pretreated mice was associated with donor leukocyte chimerism and apoptosis of graft-infiltrating cells, if these end points were similar to those in the spontaneously tolerant liver transplant model, and whether the pretreatment effect was dependent on sustained inhibition of CM expression of the infused immature donor DC. In addition, apoptosis was assessed in the host spleen and lymph nodes, a critical determination not reported in previous studies of either spontaneous or 'treatment-aided' organ tolerance models. Methods. Seven days before transplantation of hearts from B10 (H-2b) donors, 2 x 106 donor- derived immature DC were infused i.v. into C3H (H-2(k)) recipient mice with or without a concomitant i.p. injection of anti-CD40L mAb. Donor cells were detected posttransplantation by immunohistochemical staining for major histocompatibility complex class II (I-Ab) in the cells of recipient lymphoid tissue. CM expression was determined by two-color labeling. Host responses to donor alloantigen were quantified by mixed leukocyte reaction, and cytotoxic T lymphocyte (CTL) assays. Apoptotic death in graft- infiltrating cells and in areas of T-dependent lymphoid tissue was visualized by terminal deoxynucleotidyltransferase-catalyzed dUTP-digoxigenin nick-end labeling and quantitative spectrofluorometry. Interleukin-2 production and localization were estimated by immunohistochemistry. Results. Compared with control heart transplantation or heart transplantation after only DC administration, concomitant pretreatment with immature donor DC and anti- CD40L mAb caused sustained elevation of donor (I-Ab+) cells (microchimerism) in the spleen including T cell areas. More than 80% of the I-Ab+ cells in combined treatment animals also were CD86+, reflecting failure of the mAb to inhibit CD40/CD80/CD86 up-regulation on immature DC in vitro after their interaction with host T cells. Donor-specific CTL activity in graft-infiltrating cells and spleen cell populations of these animals was present on day 8, but decreased strikingly to normal control levels by day 14. The decrease was associated with enhanced apoptosis of graft-infiltrating cells and of cells in the spleen where interleukin-2 production was inhibited. The highest levels of splenic microchimerism were found in mice with long surviving grafts (> 100 days). In contrast, CTL activity was persistently elevated in control heart graft recipients with comparatively low levels of apoptotic activity and high levels of interleukin-2. Conclusion. The donor-specific acceptance of rejection-prone heart allografts by recipients pretreated with immature donor DC and anti-CD40L mAb is not dependent on sustained inhibition of donor DC CM (CD86) expression. Instead, the pretreatment facilitates a tolerogenic cascade similar to that in spontaneously tolerant liver recipients that involves: (1) chimerism-driven immune activation, succeeded by deletion of host immune responder cells by apoptosis in the spleen and allograft that is linked to interleukin-2 deficiency in both locations and (2) persistence of comparatively large numbers of donor-derived leukocytes. These tolerogenic mechanisms are thought to be generic, explaining the tolerance induced by allografts spontaneously, or with the aid of various kinds of immunosuppression

A selective and potent CXCR3 antagonist SCH 546738 attenuates the development of autoimmune diseases and delays graft rejection

<p>Abstract</p> <p>Background</p> <p>The CXCR3 receptor and its three interferon-inducible ligands (CXCL9, CXCL10 and CXCL11) have been implicated as playing a central role in directing a Th1 inflammatory response. Recent studies strongly support that the CXCR3 receptor is a very attractive therapeutic target for treating autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis and psoriasis, and to prevent transplant rejection. We describe here the in vitro and in vivo pharmacological characterizations of a novel and potent small molecule CXCR3 antagonist, SCH 546738.</p> <p>Results</p> <p>In this study, we evaluated in vitro pharmacological properties of SCH 546738 by radioligand receptor binding and human activated T cell chemotaxis assays. In vivo efficacy of SCH 546738 was determined by mouse collagen-induced arthritis, rat and mouse experimental autoimmune encephalomyelitis, and rat cardiac transplantation models. We show that SCH 546738 binds to human CXCR3 with a high affinity of 0.4 nM. In addition, SCH 546738 displaces radiolabeled CXCL10 and CXCL11 from human CXCR3 with IC₅₀ranging from 0.8 to 2.2 nM in a non-competitive manner. SCH 546738 potently and specifically inhibits CXCR3-mediated chemotaxis in human activated T cells with IC₉₀about 10 nM. SCH 546738 attenuates the disease development in mouse collagen-induced arthritis model. SCH 546738 also significantly reduces disease severity in rat and mouse experimental autoimmune encephalomyelitis models. Furthermore, SCH 546738 alone achieves dose-dependent prolongation of rat cardiac allograft survival. Most significantly, SCH 546738 in combination with CsA supports permanent engraftment.</p> <p>Conclusions</p> <p>SCH 546738 is a novel, potent and non-competitive small molecule CXCR3 antagonist. It is efficacious in multiple preclinical disease models. These results demonstrate that therapy with CXCR3 antagonists may serve as a new strategy for treatment of autoimmune diseases, including rheumatoid arthritis and multiple sclerosis, and to prevent transplant rejection.</p

The Integrated WRF/Urban Modeling System: Development, Evaluation, and Applications to Urban Environmental Problems

To bridge the gaps between traditional mesoscale modeling and microscale modeling, the National Center for Atmospheric Research (NCAR), in collaboration with other agencies and research groups, has developed an integrated urban modeling system coupled to the Weather Research and Forecasting (WRF) model as a community tool to address urban environmental issues. The core of this WRF/urban modeling system consists of: 1) three methods with different degrees of freedom to parameterize urban surface processes, ranging from a simple bulk parameterization to a sophisticated multi-layer urban canopy model with an indoor outdoor exchange sub-model that directly interacts with the atmospheric boundary layer, 2) coupling to fine-scale Computational Fluid Dynamic (CFD) Reynolds-averaged Navier–Stokes (RANS) and Large-Eddy Simulation (LES) models for Transport and Dispersion (T&D) applications, 3) procedures to incorporate high-resolution urban land-use, building morphology, and anthropogenic heating data using the National Urban Database and Access Portal Tool (NUDAPT), and 4) an urbanized high-resolution land-data assimilation system (u-HRLDAS). This paper provides an overview of this modeling system; addresses the daunting challenges of initializing the coupled WRF/urban model and of specifying the potentially vast number of parameters required to execute the WRF/urban model; explores the model sensitivity to these urban parameters; and evaluates the ability of WRF/urban to capture urban heat islands, complex boundary layer structures aloft, and urban plume T&D for several major metropolitan regions. Recent applications of this modeling system illustrate its promising utility, as a regional climate-modeling tool, to investigate impacts of future urbanization on regional meteorological conditions and on air quality under future climate change scenarios