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Epalinges, Switzerland

Puppo F.,Ecole Polytechnique Federale de Lausanne | Doucey M.-A.,Ludwig Center for Cancer Research | Delaloye J.-F.,Center du Sein | Moh T.S.Y.,Technical University of Delft | And 4 more authors.
Proceedings of IEEE Sensors | Year: 2014

Sensitive analysis of proteins is central to disease diagnosis. Their detection and investigation in the tumor tissue can further improve the level of knowledge of the cancer disease by capturing the tumor microenvironment. In previous works we demonstrated that high quality Silicon Nanowire Field Effect Transistors (SiNW-FETs) can be used to sense very low concentration (fM) of pathogenic factors in controlled Phosphate Buffered Saline (PBS). In this work we show, SiNW-FETs as biosensors for the detection of bioanalytes in tumor extract. In particular, we achieved the detection of exogenously added rabbit antigen in a much more complex environment, i.e. a human breast tumor extract. Our results show specific and high sensitive antigen detection with p-type SiNW-FETs in the range of 5-200 fM. Further and most importantly, the wires sense rabbit antigen molecules in the presence of a 100 000 mass excess of non-specific protein, indicating that the sensor is extremely resistant to noise. © 2014 IEEE. Source

Tzouvadaki I.,Ecole Polytechnique Federale de Lausanne | Puppo F.,Ecole Polytechnique Federale de Lausanne | Doucey M.-A.,Ludwig Center for Cancer Research | De Micheli G.,Ecole Polytechnique Federale de Lausanne | Carrara S.,Ecole Polytechnique Federale de Lausanne
2015 IEEE SENSORS - Proceedings | Year: 2015

In the present work, a computational study is carried out investigating the relationship between the biosensing and the electrical characteristics of two-terminal Schottky-barrier silicon nanowire devices. The model suggested successfully reproduces computationally the experimentally obtained electrical behavior of the devices prior to and after the surface bio-modification. Throughout modeling and simulations, it is confirmed that the nanofabricated devices present electrical behavior fully equivalent to that of a memristor device, according to literature. Furthermore, the model introduced successfully reproduces computationally the voltage gap appearing in the current to voltage characteristics for nanowire devices with bio-modified surface. Overall, the present study confirms the implication of the memristive effect for bio sensing applications, therefore demonstrating the Memristive Biosensors. © 2015 IEEE. Source

Etzrodt M.,Harvard University | Cortez-Retamozo V.,Harvard University | Newton A.,Harvard University | Zhao J.,California Institute of Technology | And 12 more authors.
Cell Reports | Year: 2012

Monocytes serve as a central defense system against infection and injury but can also promote pathological inflammatory responses. Considering the evidence that monocytes exist in at least two subsets committed to divergent functions, we investigated whether distinct factors regulate the balance between monocyte subset responses in vivo. We identified a microRNA (miRNA), miR-146a, which is differentially regulated both in mouse (Ly-6Chi/Ly-6Clo) and human (CD14hi/CD14loCD16+) monocyte subsets. The single miRNA controlled the amplitude of the Ly-6Chi monocyte response during inflammatory challenge whereas it did not affect Ly-6Clo cells. miR-146a-mediated regulation was cell-intrinsic and depended on Relb, a member of the noncanonical NF-κB/Rel family, which we identified as a direct miR-146a target. These observations not only provide mechanistic insights into the molecular events that regulate responses mediated by committed monocyte precursor populations but also identify targets for manipulating Ly-6Chi monocyte responses while sparing Ly-6Clo monocyte activity. Source

Gillessen S.,Kantonsspital | Gnad-Vogt U.S.,Merck KGaA | Gnad-Vogt U.S.,CureVac GmbH | Gallerani E.,Oncology Institute of Southern Switzerland | And 11 more authors.
European Journal of Cancer | Year: 2013

Background: EMD 521873 (Selectikine), an immunocytokine comprising a DNA-targeting antibody, aimed at tumour necrosis, fused with a genetically modified interleukin-2 (IL-2) moiety, was investigated in this first-in-human phase I study. Methods: Patients had metastatic or locally advanced solid tumours failing previous standard therapy. Selectikine was administered as a 1-hour intravenous infusion on 3 consecutive days, every 3 weeks. A subgroup of patients also received 300 mg/m2 cyclophosphamide on day 1 of each cycle. Escalating doses of Selectikine were investigated with the primary objective of determining the maximum tolerated dose (MTD). Results: Thirty-nine patients were treated with Selectikine alone at dose levels from 0.075 to 0.9 mg/kg, and nine were treated at doses of 0.45 and 0.6 mg/kg in combination with cyclophosphamide. A dose-dependent linear increase of peak serum concentrations and area under curve was found. The dose-limiting toxicity was grade 3 skin rash at the 0.9 mg/kg dose-level; the MTD was 0.6 mg/kg. Rash and flu-like symptoms were the most frequent side-effects. No severe cardiovascular side-effects (hypotension or vascular leak) were observed. At all dose-levels, transient increases in total lymphocyte, eosinophil and monocyte counts were recorded. No objective tumour responses, but long periods of disease stabilisation were observed. Transient and non-neutralising Selectikine antibodies were detected in 69% of patients. Conclusions: The MTD of Selectikine with or without cyclophosphamide administered under this schedule was 0.6 mg/kg. The recommended phase II dose was 0.45-0.6 mg/kg. Selectikine had a favourable safety profile and induced biological effects typical for IL-2. © 2012 Elsevier Ltd. All rights reserved. Source

Ivanov K.I.,University of Lausanne | Ivanov K.I.,University of Helsinki | Agalarov Y.,University of Lausanne | Valmu L.,University of Helsinki | And 15 more authors.
Molecular and Cellular Biology | Year: 2013

One of the key mechanisms linking cell signaling and control of gene expression is reversible phosphorylation of transcription factors. FOXC2 is a forkhead transcription factor that is mutated in the human vascular disease lymphedema-distichiasis and plays an essential role in lymphatic vascular development. However, the mechanisms regulating FOXC2 transcriptional activity are not well understood. We report here that FOXC2 is phosphorylated on eight evolutionarily conserved proline-directed serine/ threonine residues. Loss of phosphorylation at these sites triggers substantial changes in the FOXC2 transcriptional program. Through genome-wide location analysis in lymphatic endothelial cells, we demonstrate that the changes are due to selective inhibition of FOXC2 recruitment to chromatin. The extent of the inhibition varied between individual binding sites, suggesting a novel rheostat-like mechanism by which expression of specific genes can be differentially regulated by FOXC2 phosphorylation. Furthermore, unlike the wild-type protein, the phosphorylation-deficient mutant of FOXC2 failed to induce vascular remodeling in vivo. Collectively, our results point to the pivotal role of phosphorylation in the regulation of FOXC2-mediated transcription in lymphatic endothelial cells and underscore the importance of FOXC2 phosphorylation in vascular development. © 2013, American Society for Microbiology. Source

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