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No description available.

The failure of the immune system to provide efficient protection against tumour cells has been considered as a major issue in immunology. It is now well established that inadequate function of the host immune system is one of the main mechanisms by which tumours escape from immune control contributing to the limited success of cancer immunotherapy. Several cell populations have been described which display immunosuppressive properties and may impede tumor-specific immunity. Among them, GR1+CD11b+ immature myeloid suppressor cells and CD4+CD25+ regulatory T cells seem to play an important role. These cells accumulate in the spleens of tumour bearing mice and patients with cancer and contribute to immunosuppression by inhibiting the function of CD8+ T cells and/or by promoting tumour angiogenesis. The aim of our work was to define the mechanisms by which a single dose of cyclophosphamide (CTX), a chemical agent commonly used in chemotherapy treatment, induces the rejection of established P815 mastocytoma. Our data show that CTX treatment leads to the selective loss of GR1medCD11b+ splenic myeloid cell producing TGF-â, a cytokine which is known to suppress antitumoral response. Furthermore, injection of CTX causes a decrease in the number of naturally occurring regulatory T cells (CD4+CD25+Foxp3+) in the spleen and the tumor. Finally, CTX treatment induces the differentiation of GR1highCD11b+ splenic myeloid cells into mature GR1highCD11b+CD11c+ (possibly dendritic cells?) which express high levels of CD11c, MHC class II and CD86 molecules. Of note, these cells are mainly detected in tumour necrosis areas. Collectively, these results suggest that CTX prevents suppressive mechanisms and induces a population of CD11c+ myeloid cells which may present tumor antigens and activate T lymphocytes, an hypothesis in line with the requirement for CD4+ cells in CTX-induced long term resistance.

The purpose of this research was to examine how attachment style and rejection interact to influence female body image. I hypothesized that women who were high in attachment anxiety would report more negative self-evaluations than women who were low in attachment anxiety. I also hypothesized that this main effect would be qualified by a significant interaction between attachment anxiety and rejection, such that highly anxious women who were rejected would report even more negative self-evaluations than highly anxious women who were not rejected. In Study One, I found that higher levels of attachment anxiety were associated with lower self-evaluations but, contrary to expectations, attachment avoidance and rejection condition interacted to influence self-evaluations. At low levels of avoidance, women in the rejection condition reported significantly higher levels of appearance state self-esteem, body esteem, and trait self-esteem than women in the non-rejection condition. However, at high levels of avoidance, women in the rejection condition reported lower levels of these three constructs than women in the non-rejection condition, although this finding was statistically significant only for appearance state self-esteem. In Study Two, my goal was to replicate and extend these unexpected findings by examining perceived partner regard and public self-awareness as potential mediators of the interaction between avoidance and rejection on self-evaluations. Although a main effect of attachment anxiety was revealed for each of the dependent measures, contrary to Study One and my hypotheses, attachment avoidance and rejection did not interact to influence any of the self-evaluation measures and, thus, no mediational analyses were performed. Importantly, I discovered that even though participants’ mean ratings of their body esteem did not change following the rejection manipulation, the degree to which highly anxious women in the rejection condition associated how they felt about their appearance and how they thought their partner perceived them was significantly stronger than that of highly anxious women in the non-rejection condition and low anxious women in either condition. Explanations for the findings found in Study One and Study Two are discussed and the implications of these findings for future research and promoting a positive body image are considered. / Thesis (Master, Psychology) -- Queen's University, 2010-08-16 20:38:45.836

Some previous work has suggested that fetal rejection may be a cause of spontaneous abortion in humans. The aim of the work presented, therefore, was to determine the influence of maternal alloantibody formation against paternal B lymphocytes, detected by the erythrocyte antibody rosette inhibition (EAI) assay, on the outcome of semi-allogeneic pregnancies. Preliminary studies indicated that EA rosette inhibition was a suitable assay for these investigations, because it detected alloantibodies directed to any major histocompatibility complex (MHC) antigen, irrespective of the ability of the antibody to fix complement; this was an important consideration because alloantibodies induced by pregnancy are often only weakly lytic. In humans it was found that antibodies to paternal B lymphocytes occurred significantly more commonly in normal primigravid and multigravid pregnancies when compared with pregnancies of similar gestation which aborted. These antibodies were shown to be directed to MHC encoded antigens by family studies, but were not removed by platelet absorption, strongly suggesting that they were not class I MHC antigens. Studies in inbred rats demonstrated that these paternal antigens were encoded by the RT1A region of the rat MHC alone. Maternal alloantibody responses to RT1A antigens appeared to be suppressive because studies using the rat kidney allograft model showed that multiparous rats with EAI antibodies to paternal strain cells enjoyed prolonged graft survival. It was also found that pregnancies in which the paternal strain differed only by RT1A antigens induced a suppressive immune response in the mother. These results suggest that immune responses to MHC encoded antigens, possibly unique, may prevent fetal rejection in some instances.

This thesis aims to place corneal allograft rejection in the context of general transplantation immunology, examine the role of lymphocyte subsets in the rejection process and consider the potential application of monoclonal antibody therapy in clinical corneal graft rejection. The literature relating to the current clinical practice of corneal grafting, with particular reference to corneal allograft rejection, is reviewed in chapter 1 to present the extent of the problem. Chapter 2 then reviews the mechanisms of allograft rejection from the literature of transplantation immunology, much of which has arisen from studies of kidney, heart, pancreatic islets and liver in animal models. The materials and methods are described in detail in chapter 3, and only the relevant experimental design is detailed in the Materials and Methods sections of the succeeding chapters. The experimental mouse model of transplanting corneal tissue into the renal subcapsular is evaluated in chapter 4, demonstrating that isografts survive indefinitely whereas allografts are rejected typically by 30 days. Pretransplant sensitisation decreased allograft survival time to 10 days. Immunohistochemistry demonstrated the presence of CD4⁺ and CD8⁺ lymphocytes and macrophages at the rejection site. Heterotopic corneal graft recipients were then treated with various monoclonal antibody regimes. Chapter 5 demonstrates that allograft survival can be increased by either anti-CD4 or anti-CD8 therapy, providing near total depletion of the respective lymphocyte subset is achieved. Xenograft rejection is shown to depend on mainly CD4⁺ lymphocytes in chapter 6, with no benefit being found of depleting the CD8⁺ subset in addition. A mild immunosuppressive effect of anti-Vβ8 monoclonal antibody is demonstrated and discussed in chapter 7. The final chapter discusses these results in the light of recent, related work in other transplant systems, and presents a case for a trial of intracameral pan-T-cell monoclonal antibody treatment.

This thesis studies in detail the dynamics of ball screw feed drives and expands understanding of the factors that impose limitations on their performance. This knowledge is then used for developing control strategies that provide adequate command following and disturbance rejection. High performance control strategies proposed in this thesis are designed for, and implemented on, a custom-made ball screw drive. A hybrid Finite Element (FE) model for the ball screw drive is developed and coded in Matlab programming language. This FE model is employed for prediction of natural frequencies, mode shapes, and Frequency Response Functions (FRFs) of the ball screw setup. The accuracy of FRFs predicted for the ball screw mechanism alone is validated against the experimental measurements obtained through impact hammer testing. Next, the FE model for the entire test setup is validated. The dynamic characteristics of the actuator current controller are also modeled. In addition, the modal parameters of the mechanical structure are extracted from measured FRFs, which include the effects of current loop dynamics. To ensure adequate command following and disturbance rejection, three motion controllers with active vibration damping capability are developed. The first is based on the sensor averaging concept which facilitates position control of the rigid body dynamics. Active damping is added to suppress vibrations. To achieve satisfactory steady state response, integral action over the tracking error is included. The stability analysis and tuning procedure for this controller is presented together with experimental results that prove the effectiveness of this method in high-speed tracking and cutting applications. The second design uses the pole placement technique to move the real component of two of the oscillatory poles further to the left along the real axis. This yields a faster rigid body response with less vibration. However, the time delay from the current loop dynamics imposes a limitation on how much the poles can be shifted to the left without jeopardizing the system???s stability. To overcome this issue, a lead filter is designed to recover the system phase at the crossover frequency. When designing the Pole Placement Controller (PPC) and the lead filter concurrently, the objective is to minimize the load side disturbance response against the disturbances. This controller is also tested in high-speed tracking and cutting experiments. The third control method is developed around the idea of using the pole placement technique for active damping of not only the first mode of vibration, but also the second and third modes as well. A Kalman filter is designed to estimate a state vector for the system, from the control input and the position measurements obtained from the rotary and linear encoders. The state estimates are then fed back to the PPC controller. Although for this control design, promising results in terms of disturbance rejection are obtained in simulations, the Nyquist stability analysis shows that the closed loop system has poor stability margins. To improve the stability margins, the McFarlane-Glover robustness optimization method is attempted, and as a result, the stability margins are improved, but at the cost of degraded performance. The practical implementation of the third controller, was, unfortunately, not successful. This thesis concludes by addressing the problem of harmonic disturbance rejection in ball screw drives. It is shown that for cases where a ball screw drive is subject to high-frequency disturbances, the dynamic positioning accuracy of the ball screw drive can be improved significantly by adopting an additional control scheme known as Adaptive Feedforward Cancellation (AFC). Details of parameter tuning and stability analysis for AFC are presented. At the end, successful implementation and effectiveness of AFC is demonstrated in applications involving time periodic or space periodic disturbances. The conclusions drawn about the effectiveness of the AFC are based on results obtained from the high-speed tracking and end-milling experiments.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

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Individuals perceiving stigma may be unwilling to seek support directly. Instead, they may use indirect strategies due to fear of rejection. Ironically, indirect seeking leads to unsupportive network responses (i.e., rejection). In Study 1, data collected from structured interviews of a sample of U.S. women in poverty (N = 116) showed that perceived poverty-related stigma was related to increased fear of rejection, which in turn partially mediated perceived stigma and indirect seeking. In Study 2, data gathered from structured interviews of a sample of U.S. abused women (N = 177) revealed that perceived abuse-related stigma was linked to increased indirect seeking, which in turn related to increased unsupportive network responses. By contrast, direct support seeking was related to increased supportive and decreased unsupportive responses.