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.     

ER Stress in ERp57 Knockout Knee Joint Chondrocytes Induces Osteoarthritic Cartilage Degradation and Osteophyte Formation

Ageing or obesity are risk factors for protein aggregation in the endoplasmic reticulum (ER) of chondrocytes. This condition is called ER stress and leads to induction of the unfolded protein response (UPR), which, depending on the stress level, restores normal cell function or initiates apoptotic cell death. Here the role of ER stress in knee osteoarthritis (OA) was evaluated. It was first tested in vitro and in vivo whether a knockout (KO) of the protein disulfide isomerase ERp57 in chondrocytes induces sufficient ER stress for such analyses. ER stress in ERp57 KO chondrocytes was confirmed by immunofluorescence, immunohistochemistry, and transmission electron microscopy. Knee joints of wildtype (WT) and cartilage-specific ERp57 KO mice (ERp57 cKO) were analyzed by indentation-type atomic force microscopy (IT-AFM), toluidine blue, and immunofluorescence/-histochemical staining. Apoptotic cell death was investigated by a TUNEL assay. Additionally, OA was induced via forced exercise on a treadmill. ER stress in chondrocytes resulted in a reduced compressive stiffness of knee cartilage. With ER stress, 18-month-old mice developed osteoarthritic cartilage degeneration with osteophyte formation in knee joints. These degenerative changes were preceded by apoptotic death in articular chondrocytes. Young mice were not susceptible to OA, even when subjected to forced exercise. This study demonstrates that ER stress induces the development of age-related knee osteoarthritis owing to a decreased protective function of the UPR in chondrocytes with increasing age, while apoptosis increases. Therefore, inhibition of ER stress appears to be an attractive therapeutic target for OA.     

Pre-adolescent children exhibit lower aerosol particle volume emissions than adults for breathing,speaking, singing and shouting

Speaking and singing are activities linked to increased aerosol particle emissions from the respiratory system, dependent on the utilized vocal intensity. As a result, these activities have experienced considerable restrictions in enclosed spaces since the onset of the COVID-19 pandemic due to the risk of infection from the SARS-CoV-2 virus, transmitted by virus-carrying aerosols. These constraints have affected public education and extracurricular activities for children as well, from in-person music instruction to children’s choirs. However, existing risk assessments for children have been based on emission measurements of adults. To address this, we measured the particle emission rates of 15 pre-adolescent children, all eight to ten years old, with a laser particle counter for the test conditions: breathing at rest, speaking, singing and shouting. Compared with values taken from 15 adults, emission rates for breathing, speaking and singing were significantly lower for children. Particle emission rates were reduced by a factor of 4.3 across all conditions, whereas emitted particle volume rates were reduced by a factor of 4.8. These data can supplement SARS-CoV-2 risk management scenarios for various school and extracurricular settings.     

Development of nanocomposites based on organically modified montmorillonite and plasticized PVC with improved barrier properties

Montmorillonite (MMT) was organically modified with tributyl citrate (TBC). Organoclays (OMMTs) were processed with diisononyl phthalate (DINP)‐plasticized polyvinyl chloride (PVC) to form polymer nanocomposites. The produced composite materials showed a contradictory change in properties to that expected of a layered silicate nanocomposite, with a decreased E‐modulus and increased gas permeability compared with a material without OMMT. It was experimentally shown that the TBC modifier was extracted from the OMMT and was dispersed in the PVC/DINP matrix, whereupon the OMMT collapsed and formed micrometer‐sized agglomerates. Further investigation revealed that TBC has a significant effect on the gas permeability and the E‐modulus, even at low additions to a DINP‐plasticized PVC. A PVC nanocomposite with the TBC acting as both the OM for MMT and as the primary plasticizer was produced. This material showed a significantly increased E‐modulus as well as a decrease in gas permeability, confirming that it is possible to develop a nanocomposite based on plasticized PVC, if both the organo‐modification of the MMT and the formulation of the matrix are carefully selected. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 42876.     

Intumescent foams—A novel flame retardant system for flexible polyurethane foams

A combination of intumescent components was evaluated as a novel flame retardant system in a flexible polyurethane foam, and the incorporation of these components gave rise to a significant enhancement of the flame retardant properties of the foam. The heat release rate was lowered at an early stage as well as throughout the fire, the total heat production was decreased and the time to ignition was prolonged. Mechanical measurements of the foam revealed enhanced properties in terms of stiffness accompanied by a large decrease in elongation at break as compared with a reference foam. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Supporting the use of guidelines and style guides in professional user interface design

The use of user-interface design knowledge such as general guidelines and environment-specific style guides can be valuable, and is increasingly required in professional user-interface design. However, conventional guidelines and style guides ( and ) in the form of documents are consistently found hard to use. We have earlier demonstrated knowledge-based critiquing to be a technically feasible way of delivering relevant and knowledge. The purpose of this study was to investigate the need and acceptability of such techniques for professional user-interface designers.

An experiment was carried out where four professional designers developed user-interface prototypes to a functional specification. The designs were evaluated using our and -based critiquing system, which identified a total of 17 deviations from style-guide requirements or design recommendations. Interviews were conducted with the designers to find the reasons for the deviations and to identify important requirements for a critiquing design-support tool. The deviation analysis points to an existing need for better ways of accessing and knowledge. The interviews indicate that the designers would find a critiquing tool valuable, provided that it leaves them in control of their work and indicates the severity of the detected deviations.     

Indentation Damage and Residual Stress Field in Alumina-Y2O3-Stabilized Zirconia Composites

Fracture features, residual stresses, and zirconia transformation are studied in indentation strength specimens of alumina-Y₂O₃-stabilized zirconia (3% mol of Y₂O₃, 3YTZP) ceramics in order to analyze the extension of the indentation damage in the bulk of the specimens. Two compositions, 5 vol% 3YTZP (A5) and 40 vol% 3YTZP (A40), have been prepared by stacking tape-casted tapes and sintering. After indentation with loads ranging from 50 to 300 N, samples were fractured in four-point bending and the fracture surfaces were characterized by scanning electron microscopy. Raman and piezospectroscopic techniques were used to determine the monoclinic zirconia fraction and the residual stresses through the fracture surfaces. In the A5 composition, the indentation damage morphology was clearly half-penny, whereas the A40 composition presented Palmqvist crack formation. Zirconia transformation was only observed in the plastically deformed zones underneath the imprints whereas there were significant residual compressive stresses outside the plastic zones due to the indentation damage. The intensity of this residual compressive field was dependent on the level of zirconia transformation due to indentation damage because zirconia transformation induced tensile stress fields superimposed on the compressive stresses.     

Effect of crude oil ageing on low salinity and low salinity surfactant flooding

Injection of brine with lower salinity than the connate brine has proven to give a moderate increase in oil recovery in sandstones. Recent research has shown that this process will significantly benefit from introducing surfactant optimised for low salinity environment.The mechanisms underlying increased recovery by low salinity brine injection are not yet fully understood. However, research to date suggests that they are related to complex crude oil/brine/rock interactions. With this in mind, the present paper investigates primarily how the extent of oil recovery from Berea sandstones subjected to long term exposure of crude oil is influenced by (1) low salinity water injection and (2) combined process low salinity water injection with surfactant flooding.Core displacement tests were conducted on four Berea cores (30 cm), two in a natural state and two that had been subject to extensive crude oil ageing at high temperature. Results obtained from different flooding steps are discussed in terms of oil recovery and effluent properties including turbidity, pH- and ion analysis (Na⁺, Mg²⁺, Ca²⁺). The results effectively illustrate that oil recoveries from the aged cores are higher during both low salinity water injection and low salinity water injection combined with surfactant flooding. An assessment of how tertiary oil recovery in aged and unaged cores varies with surfactant concentration is also presented.Effluent ion analysis from low salinity water floods showed that Mg²⁺ ions were strongly retained in the aged core while Ca²⁺ ions were being produced from both aged and unaged cores. The latter was attributed mainly to calcite dissolution. Results obtained from pressure profiles, effluent ion analysis and turbidity tests suggest higher production and elution of fine particles from the unaged core.     

无线技术拓展过程控制的视野

使用新型的无线技术，能够方便快捷地采集和传递以往难以访问的现场数据，这无疑为现代过程控制领域打开了一个视野更为开阔的窗口。