A comparison of mono and multivalent linkers and their effect on the colloidal stability of nanoparticle and immunoassays performance

When designing devices for biomedical diagnostics, increasing the signal to noise ratio is often critical for achieving clinically relevant sensitivity and limits of detection (LOD). In antibody-based assays, the measured signal can be amplified through the replacement of molecular fluorophores with doped nanoparticles (NP). However, the benefits of using NPs can only be realized if the NPs are coated efficiently with detection antibody, have good colloidal stability and the ratio of specific to non-specific binding (NSB) is high enough. The main focus of this paper is on the optimization of the bioconjugation protocol for antibody labeling of NPs leading to improved assay performance. Two types of linkers were used: monovalent linkers (glutaraldehyde; sulfo-SMCC; and sulfo-SIAB), and three generations of dendrimers endowed with multivalent carboxylic functionality. Overall, the NP-IgG conjugates prepared using multivalent linkers showed a significantly lower LOD and higher sensitivity than their homo- or hetero-functional counterparts. The multivalent dendrimers also improved NP stability and reduced aggregation. Moreover, the dendrimers showed a higher reactivity with biological material, a feature that could significantly reduce the cost of high-throughput biodiagnostics tests. © 2010 Elsevier B.V. All rights reserved

Synthesis and biological studies of new quinazolines with ether functions in position 2

International audienc

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Evidence for widespread hydrated minerals on asteroid (101955) Bennu

Early spectral data from the Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer (OSIRIS-REx) mission reveal evidence for abundant hydrated minerals on the surface of near-Earth asteroid (101955) Bennu in the form of a near-infrared absorption near 2.7 µm and thermal infrared spectral features that are most similar to those of aqueously altered CM-type carbonaceous chondrites. We observe these spectral features across the surface of Bennu, and there is no evidence of substantial rotational variability at the spatial scales of tens to hundreds of metres observed to date. In the visible and near-infrared (0.4 to 2.4 µm) Bennu’s spectrum appears featureless and with a blue (negative) slope, confirming previous ground-based observations. Bennu may represent a class of objects that could have brought volatiles and organic chemistry to Earth

The dynamic geophysical environment of (101955) Bennu based on OSIRIS-REx measurements

The top-shaped morphology characteristic of asteroid (101955) Bennu, often found among fast-spinning asteroids and binary asteroid primaries, may have contributed substantially to binary asteroid formation. Yet a detailed geophysical analysis of this morphology for a fast-spinning asteroid has not been possible prior to the Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer (OSIRIS-REx) mission. Combining the measured Bennu mass and shape obtained during the Preliminary Survey phase of the OSIRIS-REx mission, we find a notable transition in Bennu’s surface slopes within its rotational Roche lobe, defined as the region where material is energetically trapped to the surface. As the intersection of the rotational Roche lobe with Bennu’s surface has been most recently migrating towards its equator (given Bennu’s increasing spin rate), we infer that Bennu’s surface slopes have been changing across its surface within the last million years. We also find evidence for substantial density heterogeneity within this body, suggesting that its interior is a mixture of voids and boulders. The presence of such heterogeneity and Bennu’s top shape are consistent with spin-induced failure at some point in its past, although the manner of its failure cannot yet be determined. Future measurements by the OSIRIS-REx spacecraft will provide insight into and may resolve questions regarding the formation and evolution of Bennu’s top-shape morphology and its link to the formation of binary asteroids

Influence du cadmium (Cd

De nombreuses publications font l'état de l'action négative du cadmium (Cd++) sur la vitellogenèse chez les poissons. Le mécanisme d'action de ce métal n'étant pas clairement établi, une étude a été entreprise afin de déterminer si l'effet du cadmium passait par une action sur l'activité biologique du récepteur des oestrogènes de la truite arc-en-ciel (rtER). Cette étude a été réalisée dans un système de levures recombinantes, exprimant de manière stable rtER, et dans des hépatocytes de truite en culture primaire. Dans la levure, rtER activé par l'oestradiol (E2) contrôle spécifiquement l'expression d'un gène rapporteur codant pour l'enzyme ß-Galactosidase. Une concentration en Cd++ de 10 µM diminue de 45 % l'expression stimulée par l'oestradiol du gène rapporteur dans les levures recombinantes. De même, dans les hépatocytes, l'expression du gène de la vitellogénine (VTG), gène sous le contrôle positif de E2, est diminuée de 65 %. Le cadmium n'affecte pas la liaison de E2 à son récepteur et seule l'activité hormonodépendante est affectée par ce métal. Les résultats de cette étude montrent que l'effet négatif du cadmium sur l'action de l'oestradiol passe vraisemblablement par une action directe de ce métal sur la fonction de transactivation hormono-dépendante de rtER

Low-power transimpedance amplifier for cryogenic integration with quantum devices

International audienc

Variability Evaluation of 28nm FD-SOI Technology at Cryogenic Temperatures down to 100mK for Quantum Computing

International audienc

Cryogenic Characterization of 28-nm FD-SOI Ring Oscillators With Energy Efficiency Optimization

International audienceExtensive electrical characterization of ring oscillators (ROs) made in high-k metal gate 28nm Fully-Depleted Silicon-on-Insulator (FD-SOI) technology is presented for a set of temperatures between 296 and 4.3K. First, delay per stage (t P), static current (I STAT), and dynamic current (I DYN) are analyzed for the case of the increase of threshold voltage (V TH) observed at low temperature. Then, the same analysis is performed by compensating V TH to a constant, temperature independent value through forward body-biasing (FBB). Energy efficiency optimization is proposed for different supply voltages (V DD) in order to find an optimal operating point combining both high RO frequencies and low power dissipation. We show that the Energy-Delay product (EDP) can be significantly reduced at low temperature by applying a forward body bias voltage (V FBB). We demonstrate that outstanding performance of RO in terms of speed (t p =37ps) and static power (7nA/stage) can be achieved at 4.3K with V DD reduced down to 0.325V. Index Terms-Cryogenic electronics, 28nm FD-SOI, ring oscillator, back-biasing, quantum computing, ultra-low-power