No description available.

Observation of some of the phenomena of tolerance to soluble protein antigens and allogeneic tissue transplants in Xenopus laevis has formed the framework of the present study. The method of larval induction of high-zone tolerance used in this laboratory has been confirmed and further analysed. Larvae treated with high doses of Human-γ-globulin (HGG) were unable to produce anti-HGG antibody after challenge. The proliferative response demonstrated in the spleens of tolerant toadlets 21 days after challenge was, however, of similar magnitude to that in normally responding animals. Adoptive transfer of high-zone tolerance specific to HGG was demonstrated by intravenous inoculation of tolerant histocompatible splenocytes simultaneously with an antigenic challenge via the dorsal lymph sac. This is indicative of the active involvement of a suppressor T-cell population. The induction of high-zone tolerance in X. laevis results in changes in spleen cell populations as demonstrated by buoyant density gradient separation. Spleen cell sub-populations taken from the separated layers were not, however, effective in the adoptive transfer of tolerance. A normal lymphocyte transfer reaction was observed in X. laevis to show a number of characteristics seen in the mammalian reaction. The use of mitomycin-C treated donor cells and early thymectomized hosts has demonstrated that the phenomenon is composed of donor and host components which are largely distinct from each other. Implantation of allogeneic larval spleens resulted in the induction of transplantation tolerance or impaired rejection in a significant proportion of skin grafted toadlets in which both the donor and host larvae were up to and including stage 51 at the time of transplantation. The implication of these results is that immunomaturity of the donor and host is important in the induction of transplantation tolerance but that other factors must also be involved.

No description available.

No description available.

One way of gaining confidence in the adequacy of fault tolerance mechanisms of a system is to test the system by injecting faults and see how the system performs under faulty conditions. This thesis investigates the issues of testing software-implemented fault tolerance mechanisms of distributed systems through fault injection. A fault injection method has been developed. The method requires that the target software system be structured as a collection of objects interacting via messages. This enables easy insertion of fault injection objects into the target system to emulate incorrect behaviour of faulty processors by manipulating messages. This approach allows one to inject specific classes of faults while not requiring any significant changes to the target system. The method differs from the previous work in that it exploits an object oriented approach of software implementation to support the injection of specific classes of faults at the system level. The proposed fault injection method has been applied to test software-implemented reliable node systems: a TMR (triple modular redundant) node and a fail-silent node. The nodes have integrated fault tolerance mechanisms and are expected to exhibit certain behaviour in the presence of a failure. The thesis describes how various such mechanisms (for example, clock synchronisation protocol, and atomic broadcast protocol) were tested. The testing revealed flaws in implementation that had not been discovered before, thereby demonstrating the usefulness of the method. Application of the approach to other distributed systems is also described in the thesis.

Designing and implementing distributed systems which continue to provide specified services in the presence of processing site and communication failures is a difficult task. To facilitate their development, distributed systems have been built assuming that their underlying hardware components are Jail-controlled, i.e. present a well defined failure mode. However, if conventional hardware cannot provide the assumed failure mode, there is a need to build processing sites or nodes, and communication infra-structure that present the fail-controlled behaviour assumed. Coupling a number of redundant processors within a replicated node is a well known way of constructing fail-controlled nodes. Computation is replicated and executed simultaneously at each processor, and by employing suitable validation techniques to the outputs generated by processors (e.g. majority voting, comparison), outputs from faulty processors can be prevented from appearing at the application level. One way of constructing replicated nodes is by introducing hardwired mechanisms to couple replicated processors with specialised validation hardware circuits. Processors are tightly synchronised at the clock cycle level, and have their outputs validated by a reliable validation hardware. Another approach is to use software mechanisms to perform synchronisation of processors and validation of the outputs. The main advantage of hardware based nodes is the minimum performance overhead incurred. However, the introduction of special circuits may increase the complexity of the design tremendously. Further, every new microprocessor architecture requires considerable redesign overhead. Software based nodes do not present these problems, on the other hand, they introduce much bigger performance overheads to the system. In this thesis we investigate alternative ways of constructing efficient fail-controlled, software based replicated nodes. In particular, we present much more efficient order protocols, which are necessary for the implementation of these nodes. Our protocols, unlike others published to date, do not require processors' physical clocks to be explicitly synchronised. The main contribution of this thesis is the precise definition of the semantics of a software based Jail-silent node, along with its efficient design, implementation and performance evaluation.

Thesis (Ph. D.)--University of Hawaii at Manoa, 1991. / Includes bibliographical references (leaves 112-124) / Microfiche. / xiv, 124 leaves, bound ill. 29 cm

Abstract Ligand biased signaling of opioid agonists for phosphorylation andregulation of μ -opioid receptors Student: Vida Basti. Supervisor: Prof Macdonald Christie. Departmement of Neuropharmacology, The University of Sydney. Examiner: Prof Ingrid Nylander. Departement of Phamacology, University of Uppsala. Opioid drugs are of great use in the medical practise. The drugs are commonly prescribed formany types of illnesses, mostly in cases of pain management. Although opioids come withmany benefits they are causing a lot of problems as well. The side effects are many andamongst these is tolerance development which may lead to abuse and addiction. Because ofthe fast tolerance development in patients, higher doses up to 10 times the therapeutic doseare being prescribed. This is a major issue in today’s society and must be addressed.Scientists are trying to figure out the mechanism behind tolerance by comparing differenttypes opioid drugs. Some opioids causes tolerance in a much faster rate than others but it isstill uncertain why and what is causing this. Two of the most commonly prescribed opioidsare oxycodone and morphine and so in this rapport these opioids are compared with respectto their capability to cause internalization in neurons. In the experiments a positive control,DAMGO, is being used as well as a negative control. The method being used is an indirectmethod of immunohistochemistry on AtT20 transfected cell culture. The results show thatOxycodone seems to cause no internalization at all in comparison to the control.

Thesis (M.E.)--Carnegie Mellon University, 1989. / "October 1989." Includes bibliographical references.

Thesis (M.S.)--Virginia Polytechnic Institute and State University, 1993. / Vita. Abstract. Includes bibliographical references (leaves 91-92). Also available via the Internet.