Microfluidic-based immunohistochemistry for breast cancer diagnosis: a comparative clinical study.

Breast cancer is a highly heterogeneous disease. The efficacy of tailored therapeutic strategies relies on the precise detection of diagnostic biomarkers by immunohistochemistry (IHC). Therefore, considering the increasing incidence of breast cancer cases, a concomitantly time-efficient and accurate diagnosis is clinically highly relevant. Microfluidics is a promising innovative technology in the field of tissue diagnostic, enabling for rapid, reliable, and automated immunostaining. We previously reported the microfluidic-based HER2 (human epidermal growth factor receptor 2) detection in breast carcinomas to greatly correlate with the HER2 gene amplification level. Here, we aimed to develop a panel of microfluidic-based IHC protocols for prognostic and therapeutic markers routinely assessed for breast cancer diagnosis, namely HER2, estrogen/progesterone receptor (ER/PR), and Ki67 proliferation factor. The microfluidic IHC protocol for each marker was optimized to reach high staining quality comparable to the standard procedure, while concomitantly shortening the staining time to 16 min-excluding deparaffinization and antigen retrieval step-with a turnaround time reduction up to 7 folds. Comparison of the diagnostic score on 50 formaldehyde-fixed paraffin-embedded breast tumor resections by microfluidic versus standard staining showed high concordance (overall agreement: HER2 94%, ER 95.9%, PR 93.6%, Ki67 93.7%) and strong correlation (ρ coefficient: ER 0.89, PR 0.88, Ki67 0.87; p < 0.0001) for all the analyzed markers. Importantly, HER2 genetic reflex test for all discordant cases confirmed the scores obtained by the microfluidic technique. Overall, the microfluidic-based IHC represents a clinically validated equivalent approach to the standard chromogenic staining for rapid, accurate, and automated breast cancer diagnosis

Efficient fabrication of high-density ensembles of color centers via ion implantation on a hot diamond substrate

Nitrogen-Vacancy (NV) centers in diamond are promising systems for quantum technologies, including quantum metrology and sensing. A promising strategy for the achievement of high sensitivity to external fields relies on the exploitation of large ensembles of NV centers, whose fabrication by ion implantation is upper limited by the amount of radiation damage introduced in the diamond lattice. In this works we demonstrate an approach to increase the density of NV centers upon the high-fluence implantation of MeV N2+ ions on a hot target substrate (>550 {\deg}C). Our results show that, with respect to room-temperature implantation, the high-temperature process increases the vacancy density threshold required for the irreversible conversion of diamond to a graphitic phase, thus enabling to achieve higher density ensembles. Furthermore, the formation efficiency of color centers was investigated on diamond substrates implanted at varying temperatures with MeV N2+ and Mg+ ions revealing that the formation efficiency of both NV centers and magnesium-vacancy (MgV) centers increases with the implantation temperature.Comment: 12 pages, 5 figure

Endoplasmic Reticulum Stress Links Oxidative Stress to Impaired Pancreatic Beta-Cell Function Caused by Human Oxidized LDL.

Elevated plasma concentration of the pro-atherogenic oxidized low density lipoprotein cholesterol (LDL) triggers adverse effects in pancreatic beta-cells and is associated with type 2 diabetes. Here, we investigated whether the endoplasmic reticulum (ER) stress is a key player coupling oxidative stress to beta-cell dysfunction and death elicited by human oxidized LDL. We found that human oxidized LDL activates ER stress as evidenced by the activation of the inositol requiring 1α, and the elevated expression of both DDIT3 (also called CHOP) and DNAJC3 (also called P58IPK) ER stress markers in isolated human islets and the mouse insulin secreting MIN6 cells. Silencing of Chop and inhibition of ER stress markers by the chemical chaperone phenyl butyric acid (PBA) prevented cell death caused by oxidized LDL. Finally, we found that oxidative stress accounts for activation of ER stress markers induced by oxidized LDL. Induction of Chop/CHOP and p58IPK/P58IPK by oxidized LDL was mimicked by hydrogen peroxide and was blocked by co-treatment with the N-acetylcystein antioxidant. As a conclusion, the harmful effects of oxidized LDL in beta-cells requires ER stress activation in a manner that involves oxidative stress. This mechanism may account for impaired beta-cell function in diabetes and can be reversed by antioxidant treatment

Rapport III.8. Aménagement complexe de bassins versants, spécialement en ce qui concerne la protection contre les inondations

A complex development scheme for the big Velika Morava catchment is briefly described, featuring storage reservoirs, river training works and erosion control measures. Although the reservoirs are designed for multi-purpose service, they will mainly be used to control flooding. The methods used to determine the storage capacity of these reservoirs and to frame suitable operating rules are described, with the accent on flood protection duties.Description sommaire de l’aménagement complexe du bassin de la Velika Morava par un système de réservoirs d’accumulation, de travaux de correction des cours d’eau et de lutte contre l’érosion. Bien qu’à fins multiples, les réservoirs serviront surtout à la protection contre les inondations. Les auteurs exposent les méthodes appliquées pour la détermination de la capacité des réservoirs et de la mise au point des consignes pour leur exploitation, tout particulièrement dans le domaine de la protection contre les inondations.Djordjevic B., Jovanovic S., Brajkovic M. Rapport III.8. Aménagement complexe de bassins versants, spécialement en ce qui concerne la protection contre les inondations. In: La prévision des crues et la protection contre les inondations. Dixièmes journées de l'hydraulique. Paris, 5, 6 et 7 juin 1968. Tome 3, 1969

Gems corals : classification and spectroscopic features

Several gem corals, belonging to the classes Hydrozoa and Anthozoa of the phylum Cnidaria, have been analyzed. These have been previously classified from a zoological point of view. In this paper surface structures, physical data, FTIR- and Raman-spectra of corals with gem potential have been investigated. Spectrophotometric characterisation proved to be a useful tool for determining the main features of the mineral phases (calcite or aragonite) and of the organic content in each sample. Chromophore complexes belonging to the caroteno-proteins of the carotenoid family also could be detected