Analysis of microRNAs in Exosomes of Breast Cancer Patients in Search of Molecular Prognostic Factors in Brain Metastases

Brain metastases are the most severe tumorous spread during breast cancer disease. They are associated with a limited quality of life and a very poor overall survival. A subtype of extracellular vesicles, exosomes, are sequestered by all kinds of cells, including tumor cells, and play a role in cell-cell communication. Exosomes contain, among others, microRNAs (miRs). Exosomes can be taken up by other cells in the body, and their active molecules can affect the cellular process in target cells. Tumor-secreted exosomes can affect the integrity of the blood-brain barrier (BBB) and have an impact on brain metastases forming. Serum samples from healthy donors, breast cancer patients with primary tumors, or with brain, bone, or visceral metastases were used to isolate exosomes and exosomal miRs. Exosomes expressed exosomal markers CD63 and CD9, and their amount did not vary significantly between groups, as shown by Western blot and ELISA. The selected 48 miRs were detected using real-time PCR. Area under the receiver-operating characteristic curve (AUC) was used to evaluate the diagnostic accuracy. We identified two miRs with the potential to serve as prognostic markers for brain metastases. Hsa-miR-576-3p was significantly upregulated, and hsa-miR-130a-3p was significantly downregulated in exosomes from breast cancer patients with cerebral metastases with AUC: 0.705 and 0.699, respectively. Furthermore, correlation of miR levels with tumor markers revealed that hsa-miR-340-5p levels were significantly correlated with the percentage of Ki67-positive tumor cells, while hsa-miR-342-3p levels were inversely correlated with tumor staging. Analysis of the expression levels of miRs in serum exosomes from breast cancer patients has the potential to identify new, non-invasive, blood-borne prognostic molecular markers to predict the potential for brain metastasis in breast cancer. Additional functional analyzes and careful validation of the identified markers are required before their potential future diagnostic use.     

A systematic comparison of PCA‐based Statistical Process Monitoring methods for high‐dimensional,time‐dependent Processes

High‐dimensional and time‐dependent data pose significant challenges to Statistical Process Monitoring. Most of the high‐dimensional methodologies to cope with these challenges rely on some form of Principal Component Analysis (PCA) model, usually classified as nonadaptive and adaptive. Nonadaptive methods include the static PCA approach and Dynamic Principal Component Analysis (DPCA) for data with autocorrelation. Methods, such as DPCA with Decorrelated Residuals, extend DPCA to further reduce the effects of autocorrelation and cross‐correlation on the monitoring statistics. Recursive Principal Component Analysis and Moving Window Principal Component Analysis, developed for nonstationary data, are adaptive. These fundamental methods will be systematically compared on high‐dimensional, time‐dependent processes (including the Tennessee Eastman benchmark process) to provide practitioners with guidelines for appropriate monitoring strategies and a sense of how they can be expected to perform. The selection of parameter values for the different methods is also discussed. Finally, the relevant challenges of modeling time‐dependent data are discussed, and areas of possible further research are highlighted. © 2016 American Institute of Chemical Engineers AIChE J, 62: 1478–1493, 2016     

The Consumption of Food Products from Linseed-Fed Animals Maintains Erythrocyte Omega-3 Fatty Acids in Obese Humans

Based on mechanistic and epidemiological data, we raise the question of the relationship between qualitative dietary polyunsaturated fatty acids (PUFA) changes and increase in obesity. In this double-blind trial, we studied the effects on 160 overweight volunteers (body mass index, BMI >30) of a 90 days experimental diet rich principally in animal fat with a low PUFA/saturated fatty acid (SFA) ratio but a low n-6/n-3 ratio, using animal products obtained from linseed-fed animals. The control diet provided less animal fat, a higher PUFA/SFA ratio and a higher n-6/n-3 ratio. Both diets excluded seafood. In the experimental group, we observed a significant increase in red blood cell (RBC) α-linolenic acid content and a slight increase in EPA and DHA derivatives, while in the control group we observed a significant reduction in EPA and DHA content. Between groups now, the difference in the three n-3 fatty acids changes in RBC was significant. This demonstrates that plasma EPA and DHA levels can be maintained without fish if products from linseed-fed animals are used. During the diets, we noted a significant reduction in weight, BMI and hip circumference within both groups of volunteers. However, no significant difference was observed between the control group and the experimental group. Interestingly, 150 days after the end of the trial (i.e., day 240), we noted a significant weight gain in the control group, whereas no significant weight gain was observed in the experimental group. This was also observed for the BMI and hip circumference. Moreover, significant differences in BMI (P < 0.05) and weight (P = 0.05) appeared between the two groups, showing in both cases a smaller increase in the experimental group. During the 90 days trial, we did not observe any differences between groups in terms of total cholesterol, HDL cholesterol, LDL cholesterol or triglycerides, suggesting that the saturate content and the P/S ratio are not as important as the n-6 and n-3 fatty acid composition.     

Environmental Testing of Caseless Ammunition

Caseless ammunition is subjected to considerable loading both prior to and during use in the weapon. In order to be able to assess the suitability of the ammunition whilst still at the development stage, the types of loading which might occur were analyzed and test methods for their laboratory simulation compiled. A small calibre caseless ammunition developed at ICT was tested on this basis. It was concluded that the simulated loadings had no detrimental effect on the ammunition.     

Empirical rock physics relationships on carbonate dry-frame elastic properties

Laboratory tests were conducted to analyze the ultrasonic velocity response to the pressure change in dry carbonate rocks from the Weyburn oilfield,Canada.Twent...     

Elektronenstrahltesten: Genauigkeit von Zeitmessungen im ps-Bereich

Übersicht Die Entwicklung integrierter Mikrowellenschaltungen für analoge und digitale Anwendungen mit hohen Geschwindigkeiten erfordert neue Meßmethoden. Für die Prozeß- und Schaltungsentwicklung ist vor allem die belastungsfreie Messung interner Signale notwendig. Die bereits bewährte Elektronenstrahlmeßtechnik konnte diesen neuen Anforderungen angepaßt werden. Zeitkritische Größen sind sowohl Signalanstiegszeiten als auch Phasenlagen verschiedener Signale zueinander. Signalanstiegszeiten können gegenwärtig bis herab zu 15 ps mit einem Fehler unter 10% gemessen werden. Für Messungen von Phasenlagen zwischen Signalen, die innerhalb von 3 Stunden aufgezeichnet wurden, ergibt sich eine Genauigkeit von±2 ps.

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Electron-beam testing: accuracy of time measurements in the ps range

Contents The development of integrated microwave circuits for analogue and digital applications with higher speeds requires new testing methods. The process and circuit development primarily require non loding measurements of internal signals. The adaptation of the proven technique of e-beam testing to these new requirements was successfull. Signal rise times as well as phase relations between different signals are critical quantities in the time scale. Presently, rise times can be measured down to 15 ps with an error of less than 10%. Measurements between signals being recorded within 3 hours are possible with an accuracy of±2 ps.

     

A comprehensive database schema integration method based on the theory of formal concepts

Integrating heterogeneous database schemata is a major task in federated database design where preexisting and heterogeneous database systems need to be integrated virtually by providing a homogenization database interface. Most proposed schema integration methods suffer from very complex result schemata and insufficient handling of extensional relations, i.e. in the way how redundant data of the input systems are dealt with. Redundancy among the input systems may thus remain undetected and, hence, remains uncontrolled.Our GIM (Generic Integration Model) method is based on the elegant and mathematically founded theory of formal concept analysis (FCA). The main idea is to integrate schemata into one formal context which is a binary relation between a set of attributes and a set of base extensions (set of potential objects). From that context we apply an FCA-algorithm to semi-automatically derive a concept lattice which we interpret as an inheritance hierarchy of classes for a homogenized schema. Thus, the integration task following our method can be supported by tools.     

X-ray absorption and emission spectroscopy of ZnO nanoparticle and highly oriented ZnO microrod arrays

The electronic structures of ZnO nanoparticles and microrod arrays are studied by O 1s X-ray absorption spectroscopy (XAS) and O Kα X-ray emission spectroscopy (XES). We show that the present LDA+U^SIC calculation approach is suitable to correct the LDA self-interaction error of the cation d-states. The atomic eigenstates of 3d in zinc and 2p in oxygen are energetically close, which induces strong Zn-3d-O-2p hybridization. This anomalous valence band cation-d-anion-p hybridization is affected when the localization of the Zn 3d-states is taken into account. Experimentally, the XES spectra show energy dependence in the spectral shape revealing selected excitations to the Zn 3d, 4s and 4p states, hybridized with O 2p states. Strong anisotropic effects are observed for the highly oriented ZnO rods, but not for the isotropic spherical nanoparticles. The nanostructured ZnO has primarily bulk XAS and XES properties.