Prognostic protein markers for triple negative breast cancer

Breast cancer is the most commonly diagnosed malignancy in women in the Western world, with 13,000 new patients each year in the Netherlands alone. Extensive research on gene expression profiling has shown that breast cancer is a mixture of biologically different disease entities, referred to as molecular subtypes. Of all molecular subtypes, particularly the triple negative phenotype associates with poor prognosis and poor patient survival. Intriguingly, only a small subgroup of triple negative tumors (25%), which metastasize to distant organs within 3 years, accounts for this poor prognosis. Currently, no clinical markers are available to identify triple negative tumors based on positive expression, to predict disease prognosis, and to target therapy against. The aim of our project was to identify prognostic protein markers for triple negative breast cancer using a comparative tissue proteomics approach. We have subjected frozen breast cancer tissue sections to LCM and prepared tryptic digests for nLC-MS analysis. Peptide abundance levels from poor prognosis samples were compared to good prognosis samples to identify differentially abundant peptides and their corresponding proteins. A selection of 34 differentially abundant proteins appeared to significantly differentiate between the two groups. Careful validation of these proteins may lead to better prediction of disease prognosis of triple negative breast cancer patients. Furthermore, functional analysis of key proteins may help unravel the biology of triple negative breast cancer and may lead to the development of new therapies against target proteins

Uncertainty Quantification of Geo-Magnetically Induced Currents in UHV Power Grid

Geo-magnetically induced currents (GICs) have attracted more attention since many Ultra-High Voltage (UHV) transmission lines have been built, or are going to be built in the world. However, when calculating GICs based on the classical model, some input parameters, such as the earth conductivity and dc resistances of the grid, are uncertain or very hard to be determined in advance. Taking this into account, the uncertainty quantification (UQ) model of the geo-electric fields and GICs is proposed in this paper. The UQ of the maximums of the geo-electric fields and GICs during storms is carried out based on the polynomial chaos (PC) method. The results of the UHV grid, 1000 kV Sanhua Grid, were presented and compared to the Monte Carlo method. The total Sobol indices are calculated by using the PC expansion coefficients. The sensitivities of geo-electric fields and GICs to the input variables are analyzed based on the total Sobol indices. Results show that the GICs and geo-electric fields can be effectively simulated by the proposed model, which may offer a better understanding of the sensitivities to input uncertain variables and further give a reasonable evaluation of the geomagnetic threat to the grid

Relationship between nutrient pollutants and suspended sediments in upper reaches of Yangtze River

AbstractIn order to study the relationship between nutrient pollutants and suspended sediments (SS) in the upper reaches of the Yangtze River and two tributaries, water samples were collected from September 1, 2010 to September 30, 2011 at the Zhutuo, Cuntang, Beibei, Wulong, Qingxichang, Wanxian, and Fengjie cross-sections. In the laboratory, the SS concentration and the concentration of SS whose particle size was smaller than 0.02 mm were measured. The phosphorus (P), nitrogen (N), and permanganate index (CODMn) concentrations in the natural water sample, the settled water sample, and two types of filtered water samples obtained through filter membranes with pore sizes of 0.02 mm and 0.45 μm were monitored synchronously. The results show that there are strong relationships between the P and CODMn concentrations and the SS concentration. P mainly exists in particulate form, while N mainly exists in dissolved form. SS whose particle size is smaller than 0.02 mm accounts for a high proportion of sediments in the Yangtze River and has a strong effect on water quality. At the seven cross-sections, the amounts of P, N, and CODMn in particulate form in the wet season are higher than in the dry season and the adsorption amounts of P, N, and CODMn per unit mass of sediment are higher in the dry season than in the wet season

Long Latency and High Variability in Accuracy-Speed of Prosaccades in Alzheimer's Disease at Mild to Moderate Stage

Background: Studying saccades is a useful tool to investigate brain function. There is still controversy regarding deficits in prosaccades in Alzheimer’s disease (AD), and a study of saccades in subjects with mild cognitive impairment (MCI) has not been published to date. Methods: We examined horizontal saccades in 10 healthy elderly, and 9 MCI and 9 AD patients. Two tasks were used: gap (fixation target extinguishes prior to target onset) and overlap (fixation stays on after target onset). Eye movements were recorded with the Skalar IRIS system. Results: (1) Latencies were shorter in the gap than in the overlap task (a gap effect) in all three groups of subjects: healthy elderly, MCI and AD; (2) for both tasks, latency of saccades was longer for AD patients than for healthy and MCI subjects, and (3) accuracy and mean velocity were normal in MCI and AD subjects, however, variability in accuracy-speed was higher for AD patients than for healthy and MCI subjects in the overlap task. Conclusions: Abnormalities in reaction time and accuracy-speed variability reflect deficits in cerebral areas involved in the triggering and execution of saccades; a saccade test can be useful to follow up the evolution of MCI subjects as some of them may develop AD disease