Improved Method of Neutron Activation Analysis for Microleakage Studies

Improvements in the neutron activation technique for studying microleakage were achieved by selecting more suitable tracers and by using a more accurate method for evaluation of the activation data. Dysprosium was the most suitable tracer; it provided the least variation in the results and allowed the fastest activation and counting procedure.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66594/2/10.1177_00220345740530022901.pd

On the General Ericksen-Leslie System: Parodi's Relation, Well-posedness and Stability

In this paper we investigate the role of Parodi's relation in the well-posedness and stability of the general Ericksen-Leslie system modeling nematic liquid crystal flows. First, we give a formal physical derivation of the Ericksen-Leslie system through an appropriate energy variational approach under Parodi's relation, in which we can distinguish the conservative/dissipative parts of the induced elastic stress. Next, we prove global well-posedness and long-time behavior of the Ericksen-Leslie system under the assumption that the viscosity $\mu_4$ is sufficiently large. Finally, under Parodi's relation, we show the global well-posedness and Lyapunov stability for the Ericksen-Leslie system near local energy minimizers. The connection between Parodi's relation and linear stability of the Ericksen-Leslie system is also discussed

Calibration of the instrumental polarization effects of SCExAO-CHARIS' spectropolarimetric mode

Instrumentatio

Melioidosis in a rural community of Western Province, Papua New Guinea

A prospective study was conducted to determine the significance of melioidosis in the Balimo district of Western Province, Papua New Guinea. During 1998, after the establishment of laboratory procedures and increasing local clinical awareness, the disease was found in 1.8% (95% CI 0.37–5.1%) of individuals presenting with fever refractory to standard treatment. The clinical incidence was 20.0 per 100 000 population (95% CI 12.2–30.9). The median age of culture-confirmed cases was 9.5 years (interquartile range 8.3–14.8 years). The seroprevalence of 747 community children in the region tested was 8.2% (95% CI 6.2–10.4%). Most individuals presented during the rainy season with a febrile disease refractory to standard treatment, sometimes mimicking tuberculosis. Some family clustering was apparent. All patients with bacteraemic melioidosis died, but treatment with the available conventional therapies of chloramphenicol, co-trimoxazole or doxycycline resulted in survival and cure in six patients with subacute/localised melioidosis. Further studies are needed to ascertain the local epidemiology and why children appear particularly at risk, as well as to establish the true extent of melioidosis in Papua New Guinea

Cranking the immunologic engine with chemotherapy: Using context to drive tumor antigen cross-presentation towards useful antitumor immunity

This review shows how tumor antigen cross-presentation is affected by the major therapeutic modalities including chemotherapy, radiotherapy, and surgery. We argue that this process could affect the way that a tumor works as its own cellular vaccine, and that it is differentially modulated by the choice of treatment

Decoding dangerous death: how cytotoxic chemotherapy invokes inflammation, immunity or nothing at all

Chemotherapy and immunotherapy can be either synergistic or antagonistic modalities in the treatment of cancer. Cytotoxic chemotherapy not only affects the tumor but also targets dividing lymphocytes, the very cells that are required to develop an immune response. For this reason, chemo- and immunotherapy have been seen as antagonistic. However, cell death can be immunogenic and the way in which chemotherapeutic drug kills a tumor cell is likely to be an important determinant of how that dying cell interacts with the immune system and whether the interaction will lead to an immune response. When a cell dies as the result of infection, the immune system responds rapidly and the system of Toll-like receptors (TLR) plays a key role in this process. In this review, we will briefly summarize the intracellular signaling pathways that link TLR ligation with immune activation and we will address the questions where and how TLRs recognize their targets

Targeting the effector site with IFN-αβ-inducing TLR ligands reactivates tumor-resident CD8 T cell responses to eradicate established solid tumors

Effective antitumor CD8 T cell responses may be activated by directly targeting the innate immune system within tumors. We investigated this response by injecting a range of TLR agonists into established tumors using a mouse model of malignant mesothelioma stably transduced with the hemagglutinin (HA) gene as a marker Ag (AB1-HA). Persistent delivery of the dsRNA mimetic poly(I:C) into established AB1-HA tumors resulted in complete tumor resolution in 40% of mice, with the remaining mice also showing a significant delay in tumor progression. Experiments in athymic nude mice along with CD8 depletion and IFN-αβ blocking studies revealed that tumor resolution required both CD8 T cells and type I IFN induction, and was associated with local changes in MHC class I expression. Surprisingly, however, tumor resolution was not associated with systemic dissemination or tumor infiltration of effector CD8 T cells. Instead, the antitumor response was critically dependent on the reactivation of tumor-resident CD8 T cell responses. These studies suggest that, once reactivated, pre-existing local CD8 T cell responses are sufficient to resolve established tumors and that in situ type I IFN is a determining factor

Tumor eradication after cyclophosphamide depends on concurrent depletion of regulatory T cells: a role for cycling TNFR2-expressing effector-suppressor T cells in limiting effective chemotherapy

Tumor cell death potentially engages with the immune system. However, the efficacy of anti-tumor chemotherapy may be limited by tumor-driven immunosuppression, e.g., through CD25+ regulatory T cells. We addressed this question in a mouse model of mesothelioma by depleting or reconstituting CD25+ regulatory T cells in combination with two different chemotherapeutic drugs. We found that the efficacy of cyclophosphamide to eradicate established tumors, which has been linked to regulatory T cell depletion, was negated by adoptive transfer of CD25+ regulatory T cells. Analysis of post-chemotherapy regulatory T cell populations revealed that cyclophosphamide depleted cycling (Ki-67hi) T cells, including foxp3+ regulatory CD4+ T cells. Ki-67hi CD4+ T cells expressed increased levels of two markers, TNFR2 and ICOS, that have been associated with a maximally suppressive phenotype according to recently published studies. This suggest that cyclophosphamide depletes a population of maximally suppressive regulatory T cells, which may explain its superior anti-tumor efficacy in our model. Our data suggest that regulatory T cell depletion could be used to improve the efficacy of anti-cancer chemotherapy regimens. Indeed, we observed that the drug gemcitabine, which does not deplete cycling regulatory T cells, eradicates established tumors in mice only when CD25+ CD4+ T cells are concurrently depleted. Cyclophosphamide could be used to achieve regulatory T cell depletion in combination with chemotherapy