Foxp3+ T cells induce Perforin-Dependent Dendritic Cell Death in Tumor-Draining Lymph Nodes.

Regulatory T (Treg) cells limit the onset of effective antitumor immunity, through yet-ill-defined mechanisms. We showed the rejection of established ovalbumin (OVA)-expressing MCA101 tumors required both the adoptive transfer of OVA-specific CD8(+) T cell receptor transgenic T cells (OTI) and the neutralization of Foxp3(+) T cells. In tumor-draining lymph nodes, Foxp3(+) T cell neutralization induced a marked arrest in the migration of OTI T cells, increased numbers of dendritic cells (DCs), and enhanced OTI T cell priming. Using an in vitro cytotoxic assay and two-photon live microscopy after adoptive transfer of DCs, we demonstrated that Foxp3(+) T cells induced the death of DCs in tumor-draining lymph nodes, but not in the absence of tumor. DC death correlated with Foxp3(+) T cell-DC contacts, and it was tumor-antigen and perforin dependent. We conclude that Foxp3(+) T cell-dependent DC death in tumor-draining lymph nodes limits the onset of CD8(+) T cell responses.

Intrinsic variability in the detection of micrometastases in lymph nodes for re-staging of colorectal cancer: effect of individual markers and tissue samples

In this study, we investigated whether (a) carcinoembryonic antigen (CEA), cytokeratin-20 (CK-20) and guanylyl cyclase C (GCC) are clinically useful markers for the molecular detection of submicroscopic metastases in colorectal cancer (CRC) and (b) whether overexpression of CEA, CK-20 and GCC can be reliably detected in formalin-fixed, paraffin-embedded tissues as well as frozen lymph nodes. We studied 175 frozen lymph nodes and 158 formalin-fixed, paraffin-embedded lymph nodes from 28 cases of CRC. CEA or CK-20 or GCC-specific polymerase chain reaction (PCR) was carried out on mRNA transcripts extracted from the nodal tissues. Ten out of I I Dukes' B CRC cases had detectable CEA and CK-20 while 6 out of 11 Dukes' B CRC cases had detectable GCC. In general, the difference of re-staged cases when comparing frozen and paraffin-embedded samples was marked; the only statistically significant correlation between frozen and paraffin tissue was for the CEA marker. Our results indicated a high incidence (>50%) of detecting micrometastases in histologically-negative lymph nodes at the molecular level. (C) 2003 Elsevier Science Ltd. All rights reserved.

Evaluating the impact of network density, hidden nodes and capture effect for throughput guarantee in multi-hop wireless networks

To optimize the performance of wireless networks, one needs to consider the impact of key factors such as interference from hidden nodes, the capture effect, the network density and network conditions (saturated versus non-saturated). In this research, our goal is to quantify the impact of these factors and to propose effective mechanisms and algorithms for throughput guarantees in multi-hop wireless networks. For this purpose, we have developed a model that takes into account all these key factors, based on which an admission control algorithm and an end-to-end available bandwidth estimation algorithm are proposed. Given the necessary network information and traffic demands as inputs, these algorithms are able to provide predictive control via an iterative approach. Evaluations using analytical comparison with simulations as well as existing research show that the proposed model and algorithms are accurate and effective.

Organising EU non-discrimination law around the nodes of ‘race’ gender and disability?

EU non-discrimination law has seen a proliferation of discrimination grounds from 2000. Dis-crimination on grounds of gender (in the field of equal pay) and on grounds of nationality (generally within the scope of application of EU law) were the only prohibited forms of discrimination in EU law, until the Treaty of Amsterdam empowered the Community to legislate in order to combat discrimination on grounds of sex, racial or ethnic origin, religion or belief, disability, age or sexual orientation (Article 13 EC). Proliferation of non-discrimination grounds is also characteristic for international and national non-discrimination law. As such, proliferation of grounds results in an increase in potential cases of “multiple discrimination” and the danger of diluting the demands of equality law by ever more multiplication of grounds. The hierarchy of equality, which has been so widely criticised in EU law, is a signifier of the latter danger.
This chapter proposes to structure the confusing field of non-discrimination grounds by organising them around nodes of discrimination fields. It will first reflect different ways of establishing hierarchies between grounds. This will be followed by a recount of different (narrow and wide) reading of grounds. A comprehensive reading of the grounds gender, ‘race’ and disability as establishing overlapping fields of discrimination grounds will be mapped out, with some examples for practical uses.