Dickkopf-related protein 1 (Dkk1) regulates the accumulation and function of myeloid derived suppressor cells in cancer

Tumor–stroma interactions contribute to tumorigenesis. Tumor cells can educate the stroma at primary and distant sites to facilitate the recruitment of heterogeneous populations of immature myeloid cells, known as myeloid-derived suppressor cells (MDSCs). MDSCs suppress T cell responses and promote tumor proliferation. One outstanding question is how the local and distant stroma modulate MDSCs during tumor progression. Down-regulation of β-catenin is critical for MDSC accumulation and immune suppressive functions in mice and humans. Here, we demonstrate that stroma-derived Dickkopf-1 (Dkk1) targets β-catenin in MDSCs, thus exerting immune suppressive effects during tumor progression. Mice bearing extraskeletal tumors show significantly elevated levels of Dkk1 in bone microenvironment relative to tumor site. Strikingly, Dkk1 neutralization decreases tumor growth and MDSC numbers by rescuing β-catenin in these cells and restores T cell recruitment at the tumor site. Recombinant Dkk1 suppresses β-catenin target genes in MDSCs from mice and humans and anti-Dkk1 loses its antitumor effects in mice lacking β-catenin in myeloid cells or after depletion of MDSCs, demonstrating that Dkk1 directly targets MDSCs. Furthermore, we find a correlation between CD15(+) myeloid cells and Dkk1 in pancreatic cancer patients. We establish a novel immunomodulatory role for Dkk1 in regulating tumor-induced immune suppression via targeting β-catenin in MDSCs

Correlation of lightning events and faults in distribution power networks: a joint research project

The paper deals with the analysis of the possible correlation between cloud-to-ground lightning discharges and relay operations inferred by using the experimental data obtained means of a measurement set-up, installed on an Italian MV distribution network, and a statistical procedure based on the coordinated use of the Italian Lightning Location System (LLS) CESI-SIRF, the monitoring systems of protection manoeuvres and an advanced simulation tool for the calculation of lightning-induced overvoltages. The procedure takes into account the uncertainties related to the estimation of lightning stroke location and current amplitude provided by the LLS. The experimental set-up, composed by a distributed monitoring system, is able to measure a-periodic voltage transients characterized by a frequency content up to 4 MHz. Three of these units have been installed in the feeder of a three-phase overhead distribution network with a total length of 21 km. The same feeder is protected with overcurrent and zero-sequence relays whose operations are recorded by a monitoring system with a 10-ms sampling time. The data collected during one year of operation of the experimental set-up have been analyzed together with the data collected by the LLS for a 144 km2 area covering the equipped feeder and its surrounding area, in order to account for all direct and indirect lightning events that may have caused a relay intervention. The data have been also used to test the calculation model. The paper eventually reports the results of the correlation analysis carried out using the mentioned procedure, which is used to evaluate the probability that a specific event, detected by the LLS and time-correlated to relay operation, may have been the cause of a flashover in the network

Lightning-correlated faults in power distribution networks

The paper deals with the correlation between lightning and distribution networks faults and/or voltage dips. In particular, the paper presents an application of a method proposed by the authors to correlate lightning events and relays operations based on the integrated use of: (i) data obtained from the Italian lightning location system (CESI-SIRF), (ii) data relevant to the Italian monitoring system of relay operation (CESI-SAM) and (iii) calculation results obtained by means of an advanced simulation tool for the accurate estimation of lightning-induced voltages on complex power networks (LIOV-EMTP). The correlation algorithm is able to take into account the uncertainty levels associated with the stroke location and peak current estimates provided by lightning location systems. The results obtained by means of LIOV-EMTP are shown to be of fundamental importance to achieve the appropriate estimation of the correlation of interest. A plus of the proposed algorithm is that it can make use, mostly during its validation/tuning phase, also of measured lightning-induced overvoltage waveforms recorded by means of a distributed monitoring system of voltage transients, which has been installed in a portion of the Italian distribution network. ©2007 IEEE

A Distributed Measurement System for Correlating Faults to Lightning in Distribution Networks

The paper describes a distributed measurement system developed for the monitoring of lightning originated transients in distribution networks. The data obtained by means of the proposed system are intended to be integrated with those provided by the Italian lightning location system and with those recorded by a monitoring system of relay operations. The paper briefly illustrates the philosophy of the measurement system, its develop as well as its set-up in a distribution network, located in a high keraunic area, in the northern region of Italy