Operational Strategies for Continuum Manipulators

We introduce a novel, intuitive user interface for continuum manipulators through the use of various joystick mappings. This user interface allows for the effective use of continuum manipulators in the lab and in the field. A novel geometric approach is developed to produce a more intuitive understanding of continuum manipulator kinematics. Using this geometric approach we derive the first closed-form solution to the inverse kinematics problem for continuum robots. Using the derived inverse kinematics to convert from workspace coordinates to configuration space coordinates we develop a potential-field path planner for continuum manipulators

Recipient‐derived EDA fibronectin promotes cardiac allograft fibrosis

Advances in donor matching and immunosuppressive therapies have decreased the prevalence of acute rejection of cardiac grafts; however, chronic rejection remains a significant obstacle for long‐term allograft survival. While initiating elements of anti‐allograft immune responses have been identified, the linkage between these factors and the ultimate development of cardiac fibrosis is not well understood. Tissue fibrosis resembles an exaggerated wound healing response, in which extracellular matrix (ECM) molecules are central. One such ECM molecule is an alternatively spliced isoform of the ubiquitous glycoprotein fibronectin (FN), termed extra domain A‐containing cellular fibronectin (EDA cFN). EDA cFN is instrumental in fibrogenesis; thus, we hypothesized that it might also regulate fibrotic remodelling associated with chronic rejection. We compared the development of acute and chronic cardiac allograft rejection in EDA cFN‐deficient (EDA −/− ) and wild‐type (WT) mice. While EDA −/− mice developed acute cardiac rejection in a manner indistinguishable from WT controls, cardiac allografts in EDA −/− mice were protected from fibrosis associated with chronic rejection. Decreased fibrosis was not associated with differences in cardiomyocyte hypertrophy or intra‐graft expression of pro‐fibrotic mediators. Further, we examined expression of EDA cFN and total FN by whole splenocytes under conditions promoting various T‐helper lineages. Conditions supporting regulatory T‐cell (Treg) development were characterized by greatest production of total FN and EDA cFN, though EDA cFN to total FN ratios were highest in Th1 cultures. These findings indicate that recipient‐derived EDA cFN is dispensable for acute allograft rejection responses but that it promotes the development of fibrosis associated with chronic rejection. Further, conditions favouring the development of regulatory T cells, widely considered graft‐protective, may drive production of ECM molecules which enhance deleterious remodelling responses. Thus, EDA cFN may be a therapeutic target for ameliorating fibrosis associated with chronic cardiac allograft rejection. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90405/1/3010_ftp.pd

Relative contribution of direct and indirect allorecognition in developing tolerance after liver transplantation

The interaction of donor passenger leukocytes and host leukocytes in recipient secondary lymphoid tissues during the early posttransplantation period is crucial in directing host immune reactions toward allograft rejection or acceptance. Responsible T cell clones could be activated through the direct and indirect pathways of allorecognition. We examined the role of the indirect pathway in liver transplantation (LT) tolerance by depleting host antigen-presenting cells (APC) with phagocytic activity [e.g., cluster domain (CD)68+/CD163+ macrophages, CD11c+ dendritic cells (DC)] using liposome-encapsulating clodronate (LP-CL). After Lewis rat cell or liver graft transplantation, Brown Norway (BN) rat recipients pretreated with LP-CL showed a significantly reduced type 1 helper T cell cytokine up-regulation than control-LP-treated recipients. In the LT model, LP-CL treatment and host APC depletion abrogated hepatic tolerance; Lewis liver grafts in LP-CL-treated-BN recipients developed mild allograft rejection, failed to maintain donor major histocompatibility complex (MHC) class II+ leukocytes, and developed chronic rejection in challenged donor heart allografts, while control-LP-treated BN recipients maintained tolerance status and donor MHC class II+ hepatic leukocytes. Furthermore, in the BN to Lewis LT model, LP-CL recipient treatment abrogated spontaneous hepatic allograft acceptance, and graft survival rate was reduced to 43% from 100% in the control-LP group. In conclusion, the study suggests that host cells with phagocytic activity could play significant roles in developing LT tolerance. © 2008 AASLD

Transforming Growth Factor-Beta1 Gene Transfer is Associated with the Development of Regulatory Cells

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73575/1/j.1600-6143.2005.01042.x.pd

Glucocorticoid-Induced TNFR-Related Protein Stimulation Reverses Cardiac Allograft Acceptance Induced by CD40-CD40L Blockade

CD40-CD40L blockade has potent immunosuppressive effects in cardiac allograft rejection but is less effective in the presence of inflammatory signals. To better understand the factors that mediate CD40-CD40L blockade-resistant rejection, we studied the effects of stimulation through glucocorticoid-induced TNFR-related protein (GITR), a costimulatory protein expressed by regulatory and effector T cells. Stimulation of CD40−/− or wild-type recipient mice treated with anti-CD40L mAb (WT+anti-CD40L) and with agonistic anti-GITR mAb resulted in cardiac allograft rejection. GITR stimulation did not induce rejection once long-term graft acceptance was established. In vitro, GITR stimulation increased proliferation of effector T cells and decreased regulatory T cell () differentiation in both treatment groups. GITR-stimulated CD40−/− recipients rejected their allografts more rapidly compared to GITR-stimulated WT+anti-CD40L recipients, and this rejection, characterized by a robust Th2 response and significant eosinophilic infiltrate, could be mediated by CD4+ T cells alone. In contrast, both CD4+ and CD8+ T cells were required to induce rejection in GITR-stimulated WT+anti-CD40L-treated recipients, and the pathology of rejection was less severe. Hence, early GITR stimulation could initiate graft rejection despite CD40 deficiency or anti-CD40L mAb treatment, though the recipient response was dependent on the mechanism of CD40-CD40L disruption

Connective Tissue Growth Factor Promotes Fibrosis Downstream of TGFΒ and IL-6 in Chronic Cardiac Allograft Rejection

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72574/1/j.1600-6143.2009.02826.x.pd

Diamond films grown from fullerene precursors

Transmission Electron Microscope (TEM) techniques are applied to study the microstructure of diamond films grown from fullerene precursors. Electron diffraction and electron energy loss spectra (EELS) collected from the diamond films correspond to that of bulk diamond. Microdiffraction, high resolution images and EELS help determine that the first diamond grains that nucleate from fullerene precursors generally form on a thin amorphous carbon interlayer and seldom directly on the silicon substrate. Grain size measurements reveal nanocrystalline diamond grains. Cross section TEM images show that the nanocrystalline diamond grains are equiaxed and not columnar nor dendritic. The microstructure of small equiaxed grains throughout the film thickness is believed responsible for the very smooth surfaces of diamond films grown from fullerene precursors

Grain boundaries and grain size distributions in nanocrystalline diamond films derived from fullerene precursors

Film growth from C{sub 60}/Ar mixtures results in very pure diamond. Diamond films grown using C{sub 60} as a carbon source have been shown to be nanocrystalline with average grain sizes of 15 nm and standard deviations of 13 nm. The measured grain size distribution for two separate films, each based on measurements of over 400 grains, were found to be very similar and well approximated by a gamma distribution. Unlike typical CVD grown diamond films, these nanocrystalline films do not exhibit columnar growth. From the measured grain size distributions, it is estimated that 2% of the carbon atoms are located in the grain boundaries. The structure of the carbon in the grain boundaries is not known, but the films survive extended wear tests and hold together when the substrate is removed, indicating that the grains are strongly bound. The grain boundary carbon may give rise to additional features in the Raman spectrum and result in absorption and scattering of light in the films. We also expect that the grain boundary carbon may affect film properties, such as electrical and thermal conductivity

Fabrication of 10 nm diameter hydrocarbon nanopores

The addition of carbon to samples, during transmission electron microscope imaging, presents a barrier to accurate analysis; the controlled deposition of hydrocarbons by a focused electron beam can be a useful technique for local nanometer-scale sculpting of material. Here we use hydrocarbon deposition to form nanopores from larger focused ion beam holes in silicon nitride membranes. Using this method, we close 100–200 nm diameter holes to diameters of 10 nm and below, with deposition rates of 0.6 nm/min. I-V characteristics of electrolytic flow through these nanopores agree quantitatively with a one dimensional model at all examined salt concentrations