Molecular characteristics of mismatch repair genes in sporadic colorectal tumors in Czech patients

BACKGROUND: Mismatch repair (MMR) genes are known to be frequently altered in colorectal cancer (CRC). Both genetics and epigenetics modifications seems to be relevant in this phenomenon, however it is still not clear how these two aspects are interconnected. The present study aimed at characterizing of epigenetic and gene expression profiles of MMR genes in sporadic CRC patients from the Czech Republic, a country with one of the highest incidences of this cancer all over Europe. METHODS: Expression levels and CpG promoter methylation status of all MMR genes were evaluated in DNA from tumor and adjacent mucosal samples of 53 incident CRC patients. RESULTS: We have found significantly increased transcription levels in EXO1 gene in tumor tissues (P = 0.05) and significant over-expression of MSH3 gene in colon tumors when compared to adjacent mucosal tissues (P = 0.02). Interestingly, almost all MMR genes were differently expressed when localization of tumors was compared. In particular, colon tumors showed an up-regulation of EXO1, MSH2, MSH3, MSH6, and PMS2 genes in comparison to rectal tumors (P = 0.02). Expression levels of all MMR genes positively correlated between each other. The promoter methylation of MLH1 gene was observed in 9% of CRC tissues only. CONCLUSIONS: In our study, we have observed different pattern of MMR genes expression according to tumor localization. However, a lack of association between methylation in MMR genes and their corresponding expressions was noticed in this study, the relationship between these two aspects is worthy to be analyzed in larger population studies and in pre-malignant stages

Magnetic Resonance Imaging Is More Sensitive Than PET for Detecting Treatment-Induced Cell Death-Dependent Changes in Glycolysis.

Metabolic imaging has been widely used to measure the early responses of tumors to treatment. Here, we assess the abilities of PET measurement of [18F]FDG uptake and MRI measurement of hyperpolarized [1-13C]pyruvate metabolism to detect early changes in glycolysis following treatment-induced cell death in human colorectal (Colo205) and breast adenocarcinoma (MDA-MB-231) xenografts in mice. A TRAIL agonist that binds to human but not mouse cells induced tumor-selective cell death. Tumor glycolysis was assessed by injecting [1,6-13C2]glucose and measuring 13C-labeled metabolites in tumor extracts. Injection of hyperpolarized [1-13C]pyruvate induced rapid reduction in lactate labeling. This decrease, which correlated with an increase in histologic markers of cell death and preceded decrease in tumor volume, reflected reduced flux from glucose to lactate and decreased lactate concentration. However, [18F]FDG uptake and phosphorylation were maintained following treatment, which has been attributed previously to increased [18F]FDG uptake by infiltrating immune cells. Quantification of [18F]FDG uptake in flow-sorted tumor and immune cells from disaggregated tumors identified CD11b+/CD45+ macrophages as the most [18F]FDG-avid cell type present, yet they represented <5% of the cells present in the tumors and could not explain the failure of [18F]FDG-PET to detect treatment response. MRI measurement of hyperpolarized [1-13C]pyruvate metabolism is therefore a more sensitive marker of the early decreases in glycolytic flux that occur following cell death than PET measurements of [18F]FDG uptake. SIGNIFICANCE: These findings demonstrate superior sensitivity of MRI measurement of hyperpolarized [1-13C]pyruvate metabolism versus PET measurement of 18F-FDG uptake for detecting early changes in glycolysis following treatment-induced tumor cell death

Analysis of the Mutual Trade Between the Eu and Indonesia

Mutual trade between EU countries and Indonesia is a bilateral commodity trade flow exceeding 17 billion Euros. Analysis of the trade between the two entities is an important contribution leading to the definition of the significance that the ongoing cooperation between the EU and Indonesia has. EU is for Indonesia very important trading partner, for EU is Indonesia a strategic political partner. The bilateral trade is currently greatly benefiting Indonesia, however, this market has a potential for EU due to the fact, that it is one of the most populous country in the Asian region and the in world in general. The trade exchange is based on export and import of most basic aggregate commodities; while between the two partners exist significant differences in terms of available comparative advantages. A specificity of the mutual trade is the limited territorial structure of this exchange, as the main volume of transactions is realized between Indonesia and only a few EU countries. Keywords: EU, Indonesia, mutual, foreign trade, commodity, territory, structure, analysis, competitivenes

A first Alps - dedicated gravity data set - introduction and status of the AlpArray gravity field activities

In this contribution, activities of the AlpArray Gravity Research Group (AAGRG) are introduced. Since 2018, this group in the frame of the AlpArray project (http://www.alparray.ethz.ch/en/home/) prepares gravity and other data sets to support multidisciplinary goals of the project. It is focused on the mantle, plate and surface processes in the Alps-Apennines-Carpathians-Dinarides orogenic system. In 2018, the AAGRG set up its own methodology guidelines and assembled available land-gravity data and digital elevation model (DEM) data from all the participating countries. Our presentation targets especially three goals: 1) to introduce AAGRG activities as an integral part of the AlpArray project for studying Alpine orogeny \u2013 a goal that by definition requires international cooperation, 2) to review the input data and the works accomplished so far, and, 3) to discuss the steps to be taken to produce detailed gravity maps of the region \u2013 the first Alps-dedicated gravity field data set. We plan to prepare gravity grids in a homogeneous processing approach of either 2x2 km or 4x4 km resolution, depending on the coverage and data quality. The final data sets will be made public in late 2019. A special emphasis is put on the calculation of the Bouguer anomaly using ellipsoidal rather tha normal heights. For calculating topographic effects the preference is given to local DEMs, where available, as they often provide higher quality and spatial resolutions. The public gravity data sets are evaluated with the high-resolution geopotential models like EIGEN-6C4 or EGM2008 \u2013 a useful means for identifying biases in the data coming from various countries and campaigns

A novel broad specificity fucosidase capable of core alpha 1-6 fucose release from N-glycans labeled with urea-linked fluorescent dyes

Host-parasite interactio

Generation of 64 GBd 4ASK signals using a silicon-organic hybrid modulator at 80°C

We demonstrate a silicon-organic hybrid (SOH) Mach-Zehnder modulator (MZM) generating four-level amplitude shift keying (4ASK) signals at symbol rates of up to 64 GBd both at room temperature and at an elevated temperature of 80°C. The measured line rate of 128 Gbit/s corresponds to the highest value demonstrated for silicon-based MZM so far. We report bit error ratios of 10−10 (64 GBd BPSK), 10−5 (36 GBd 4ASK), and 4 × 10−3 (64 GBd 4ASK) at room temperature. At 80 °C, the respective bit error ratios are 10−10, 10−4, and 1.3 × 10−2. The high-temperature experiments were performed in regular oxygen-rich ambient atmosphere

Machine Learning for Health: Algorithm Auditing & Quality Control

Developers proposing new machine learning for health (ML4H) tools often pledge to match or even surpass the performance of existing tools, yet the reality is usually more complicated. Reliable deployment of ML4H to the real world is challenging as examples from diabetic retinopathy or Covid-19 screening show. We envision an integrated framework of algorithm auditing and quality control that provides a path towards the effective and reliable application of ML systems in healthcare. In this editorial, we give a summary of ongoing work towards that vision and announce a call for participation to the special issue Machine Learning for Health: Algorithm Auditing & Quality Control in this journal to advance the practice of ML4H auditing

Organic food sourcing, processing and distribution: a case of satisfying a growing market

A case study of an organic food company in the Slovak Republic involved in producing and sourcing inputs, food processing and distribution is presented. The case is based on a June 2014 “live” case study prepared for students in International MBA in Agribusiness programs at the Slovak University of Agriculture in Nitra, Warsaw University of Life Sciences and the National University of Life and Environmental Sciences of Ukraine, Kiev. The company was established in 2001 with the objective to bring organic food to health conscious consumers. The company grows organic spelt grain, wheat, rye, buckwheat, herbs and apples on its 156 ha and 400 ha of owned and rented farmland. The company further processes these crops into more than 40 finished products. Students are presented with company information and summaries of a company visit and discussions with management. Students perform PEST and SWOT analyses, identify a shortage of owned and leased land as a problem the company must address, conduct research and analysis, and recommend product specification contracts as a solution to the problem