Injection létale | EPFL Graph Search

L'injection létale est une méthode d'exécution qui consiste à injecter un ou plusieurs produits à un condamné afin de lui ôter la vie. Depuis 1982, plusieurs milliers de personnes auraient ainsi été exécutées par injection mortelle dans le monde : trois au Guatemala, six en Thaïlande, sept aux Philippines, plus de aux États-Unis et jusqu’à plusieurs milliers en Chine. Histoire Le docteur Julius Mount Bleyer proposa cette méthode d'exécution dès 1888, à New York, mais celle-ci ne fut pas acceptée. À la suite des pressions de la British Medical Association, elle fut également rejetée au Royaume-Uni. Le premier État des États-Unis à l'adopter fut l'Oklahoma, en février 1977, sous l'impulsion du docteur Stanley Deutsch, suivi du Texas la même année. Ce dernier l'appliqua la première fois le lors de l'exécution de Charles Brooks. Depuis, la quasi-totalité des États ayant recours à la peine de mort utilisent ce mode d'exécution. Elle est considérée par ses partisans comme une

Role of RIP4 in lung adenocarcinoma differentiation

Jawahar Kopparam

Various studies have attributed NF-kB activation to promote KRAS mediated non-small cell lung cancer progression. In order to identify key genes regulating NF-kB activation and cell survival in lung adenocarcinoma, a synthetic lethal partner screen for KRAS was conducted in cell lines expressing mutant or wildtype KRAS. This screen identified an important role of Receptor-interacting serine/threonine protein kinase 4 (RIP4) in KRAS mediated oncogenesis. But altering RIP4 expression did not affect the viability of KRAS mutant cells, however a novel role of RIP4 in maintaining tumor differentiation was observed. Loss of epithelial differentiation and extracellular matrix remodeling are known to facilitate cancer progression and are associated with poor prognosis in patients with lung cancer. Bioinformatics analyses of human lung adenocarcinoma samples showed that poorly differentiated tumors express low levels of RIP4, whereas high levels are associated with better overall survival. Interleukin 6 (IL6) signaling is activated in lung adenocarcinoma expressing oncogenic KRAS and contributes to cancer invasiveness. Knockdown of RIP4 using shRNA in vitro enhanced activation of IL-6 signaling and also the ability of the cells to invade through collagen. In contrast, overexpression of RIP4 inhibited IL6-mediated Signal Transducer and activator of Transcription 3 (STAT3) activation, which abrogated IL6-dependent induction of lysyl oxidase, a collagen cross-linking enzyme. Tumor-specific Rip4 knockdown in an autochthonous mouse model of lung adenocarcinoma initiated by Kras(G12D) expression with loss of p53, progressed to a poorly differentiated state marked by an increase in Hmga2, reduced Ttf1 and enrichment of genes regulating extracellular matrix (ECM) remodeling and JAK-STAT signaling. Activated STAT3 can enhance NF-kB activation by interacting with NF-kB and promoting its nuclear retention. Tumors with RIP4 knockdown also exhibited enhanced STAT3- NF-kB interaction suggesting a cross talk between the two pathways. Tail vein injections of cells overexpressing RIP4 showed a reduced potential to invade and form tumors. Analysis of factors regulating RIP4 expression revealed that RIP4 is induced in a p53 dependent manner in response to chemotherapy. Altering the induced RIP4 levels in vitro had a modest effect on chemotherapy induced cell death. Our work has identified that loss of RIP4 enhances IL6 signaling in lung cancer cells, promoting the expression of ECM remodeling genes and cancer dedifferentiation.

EPFL2016

Capacitive sensor to monitor the level of drug inside an injector pen

Sylvain Paul Fernand Joly

Diabete is a disease which is spreading faster than ever, impacting now a larger population. Patients suffering from this disease need the injection of insulin to control extracellular sugar levels. Pharmaceutical companies developed injector pens to allow patients to inject themself the right amount of drug. But the dosage depends on many parameters as the previous meal, current blood sugar level... and a wrong dosage can lead to health problem e.g., loss of conciousness at short terms and severe diseases like cardiac pathologies at long terms... To prevent these situations, a smart pen cap has been developed at Valtronic Technologies to follow and log the individual injections by measuring the level of drug in the pen, the temperature, and the relative humidity to allow the patient and the medical staff to have an history of the injections and the climatic conditions.Injector pen and smart pen cap have been firstly presented with a non-exhaustive list of different physics which can be used to measure a level of liquid. For need of precision, the capacitance technique is the best technology choice. Therefore, the smart pen cap is based on a capacitive sensor. Different capacitance converter topologies have been compared through a bibliographic study. It appears that the Lock-in converter gives the best sensitivity and Charge Sensitivity Amplifier has the lowest power consumption. A trade-of was to use a capacitance-to-digital-converter. A chip from Analog device has been selected due to its high resolution below the femto-farad level, its simple interface and its availability on the market which allows a fast development and industrialisation. Then, switch and electronic structure are presented. First tests with an empty device have been conducted to find the noise floor, which is below 0.1fF.Subsequently, a study of different electrodes configuration has been performed. Firstly, an analysis on two parallel flat electrodes has been conducted using theoretical and simulation approaches. Then, two semi-cylindrical electrodes have been analysed. A comparison has been made between two theoretical methods which are: considering an infinite number of parallel flat electrodes following the shape of the semi-cylindrical electrodes and the conformal mapping methods. This last method gives coherent results when comparing real measurements and simulation. The device is equipped with semi-cylindrical electrodes which allow for a small package and a good correlation between capacitance and drug level with a convertion slope of 0.5fF/µL. Tests have been performed which give an error of +-1 IU and +-4 IU for large injection (set point equal to 72 IU).Finally, the study of some parasitic effects is presented in the last section. An important effect is the climatic effect which affects the capacitance due to variation of electric permittivity linked to temperature change and water absorption of certain materials as plastics. To compensate for this effect, reference electrodes and a climatic sensor have been implemented. Another important effect comes from the cartridge position in the non-uniform electric field of the smart pen cap. A four electrodes device has been realized to allow a perpendicular rotation of the electric field to obtain a more constant averaged electric field. As a consequence, the position impact of the cartridge has been reduced. Other effects have been considered. The device can detect a minimum injection of 52uL.

EPFL2021

Capacitive sensor to monitor the level of drug inside an injector pen

Sylvain Paul Fernand Joly

EPFL2021

Role of RIP4 in lung adenocarcinoma differentiation

Jawahar Kopparam

EPFL2016