On the determination of Poisson's ratio of stressed monolayer and bilayer submicron thick films

In this paper, the bulge test is used to determine the mechanical properties of very thin dielectric membranes. Commonly, this experimental method permits to determine the residual stress (s0) and biaxial Young's modulus (E/(1-u)). Associating square and rectangular membranes with different length to width ratios, the Poisson's ratio (u) can also be determined. LPCVD Si3N4 monolayer and Si3N4/SiO2 bilayer membranes, with thicknesses down to 100 nm, have been characterized giving results in agreement with literature for Si3N4, E = 212 $\pm$ 14 GPa, s0 = 420 $\pm$ 8 and u = 0.29.Comment: Submitted on behalf of EDA Publishing Association (http://irevues.inist.fr/handle/2042/16838

Micro-tensile tests on micromachined metal on polymer specimens: elasticity, plasticity and rupture

This study is focused on the mechanical characterization of materials used in microelectronic and micro- electromechanical systems (MEMS) devices. In order to determine their mechanical parameters, a new deformation bench test with suitable micromachined specimens have been developed. Uniaxial tensile tests were performed on "low cost" specimens, consisting in electroplated thin copper films and structures, deposited on a polimide type substrate. Moreover, a cyclic mechanical actuation via piezoelectric actuators was tested on the same deformation bench. These experiments validate the device for performing dynamic characterization of materials, and reliability studies of different microstructures.Comment: Submitted on behalf of EDA Publishing Association (http://irevues.inist.fr/handle/2042/16838

Ovarian-Adnexal Reporting Data System Magnetic Resonance Imaging (O-RADS MRI) score for risk stratification of sonographically indeterminate adnexal masses.

Importance: Approximately one-quarter of adnexal masses detected at ultrasonography are indeterminate for benignity or malignancy, posing a substantial clinical dilemma. Objective: To validate the accuracy of a 5-point Ovarian-Adnexal Reporting Data System Magnetic Resonance Imaging (O-RADS MRI) score for risk stratification of adnexal masses. Design, Setting, and Participants: This multicenter cohort study was conducted between March 1, 2013, and March 31, 2016. Among patients undergoing expectant management, 2-year follow-up data were completed by March 31, 2018. A routine pelvic MRI was performed among consecutive patients referred to characterize a sonographically indeterminate adnexal mass according to routine diagnostic practice at 15 referral centers. The MRI score was prospectively applied by 2 onsite readers and by 1 reader masked to clinical and ultrasonographic data. Data analysis was conducted between April and November 2018. Main Outcomes and Measures: The primary end point was the joint analysis of true-negative and false-negative rates according to the MRI score compared with the reference standard (ie, histology or 2-year follow-up). Results: A total of 1340 women (mean [range] age, 49 [18-96] years) were enrolled. Of 1194 evaluable women, 1130 (94.6%) had a pelvic mass on MRI with a reference standard (surgery, 768 [67.9%]; 2-year follow-up, 362 [32.1%]). A total of 203 patients (18.0%) had at least 1 malignant adnexal or nonadnexal pelvic mass. No invasive cancer was assigned a score of 2. Positive likelihood ratios were 0.01 for score 2, 0.27 for score 3, 4.42 for score 4, and 38.81 for score 5. Area under the receiver operating characteristic curve was 0.961 (95% CI, 0.948-0.971) among experienced readers, with a sensitivity of 0.93 (95% CI, 0.89-0.96; 189 of 203 patients) and a specificity of 0.91 (95% CI, 0.89-0.93; 848 of 927 patients). There was good interrater agreement among both experienced and junior readers (κ = 0.784; 95% CI, 0.743-0824). Of 580 of 1130 women (51.3%) with a mass on MRI and no specific gynecological symptoms, 362 (62.4%) underwent surgery. Of them, 244 (67.4%) had benign lesions and a score of 3 or less. The MRI score correctly reclassified the mass origin as nonadnexal with a sensitivity of 0.99 (95% CI, 0.98-0.99; 1360 of 1372 patients) and a specificity of 0.78 (95% CI, 0.71-0.85; 102 of 130 patients). Conclusions and Relevance: In this study, the O-RADS MRI score was accurate when stratifying the risk of malignancy in adnexal masses

Development of subtype-selective photoswitchable positive allosteric modulators for mGlu receptors

Positive allosteric modulators (PAMs) for metabotropic glutamate receptors have been postulated to treat neuropsychiatric diseases. Besides, obtaining a reversible and efficient spatiotemporal control of mGlu activity would be therapeutically advantageous. Photopharmacology may provide a solution on this topic, since it is based on the use of light and photoswitchable ligands to modulate a protein activity. This approach offers new perspectives for drug discovery and promises a better drug action control reducing side effects to unattained levels.Peer reviewe

Functioning of the dimeric GABA(B) receptor extracellular domain revealed by glycan wedge scanning

The G-protein-coupled receptor (GPCR) activated by the neurotransmitter GABA is made up of two subunits, GABA(B1) and GABA(B2). GABA(B1) binds agonists, whereas GABA(B2) is required for trafficking GABA(B1) to the cell surface, increasing agonist affinity to GABA(B1), and activating associated G proteins. These subunits each comprise two domains, a Venus flytrap domain (VFT) and a heptahelical transmembrane domain (7TM). How agonist binding to the GABA(B1) VFT leads to GABA(B2) 7TM activation remains unknown. Here, we used a glycan wedge scanning approach to investigate how the GABA(B) VFT dimer controls receptor activity. We first identified the dimerization interface using a bioinformatics approach and then showed that introducing an N-glycan at this interface prevents the association of the two subunits and abolishes all activities of GABA(B2), including agonist activation of the G protein. We also identified a second region in the VFT where insertion of an N-glycan does not prevent dimerization, but blocks agonist activation of the receptor. These data provide new insight into the function of this prototypical GPCR and demonstrate that a change in the dimerization interface is required for receptor activation