Perceval: A Software Platform for Discrete Variable Photonic Quantum Computing

We introduce Perceval, an evolutive open-source software platform for simulating and interfacing with discrete variable photonic quantum computers, and describe its main features and components. Its Python front-end allows photonic circuits to be composed from basic photonic building blocks like photon sources, beam splitters, phase shifters and detectors. A variety of computational back-ends are available and optimised for different use-cases. These use state-of-the-art simulation techniques covering both weak simulation, or sampling, and strong simulation. We give examples of Perceval in action by reproducing a variety of photonic experiments and simulating photonic implementations of a range of quantum algorithms, from Grover's and Shor's to examples of quantum machine learning. Perceval is intended to be a useful toolkit both for experimentalists wishing to easily model, design, simulate, or optimise a discrete variable photonic experiment, and for theoreticians wishing to design algorithms and applications for discrete-variable photonic quantum computing platforms

Amphiphilic block copolymers enhance the cellular uptake of DNA molecules through a facilitated plasma membrane transport

Amphiphilic block copolymers have been developed recently for their efficient, in vivo transfection activities in various tissues. Surprisingly, we observed that amphiphilic block copolymers such as Lutrol® do not allow the transfection of cultured cells in vitro, suggesting that the cell environment is strongly involved in their mechanism of action. In an in vitro model mimicking the in vivo situation we showed that pre-treatment of cells with Lutrol®, prior to their incubation with DNA molecules in the presence of cationic lipid, resulted in higher levels of reporter gene expression. We also showed that this improvement in transfection efficiency associated with the presence of Lutrol® was observed irrespective of the plasmid promoter. Considering the various steps that could be improved by Lutrol®, we concluded that the nucleic acids molecule internalization step is the most important barrier affected by Lutrol®. Microscopic examination of transfected cells pre-treated with Lutrol® confirmed that more plasmid DNA copies were internalized. Absence of cationic lipid did not impair Lutrol®-mediated DNA internalization, but critically impaired endosomal escape. Our results strongly suggest that in vivo, Lutrol® improves transfection by a physicochemical mechanism, leading to cellular uptake enhancement through a direct delivery into the cytoplasm, and not via endosomal pathways

Probing the in vitro mechanism of action of cationic lipid/DNA lipoplexes at a nanometric scale

Cationic lipids are used for delivering nucleic acids (lipoplexes) into cells for both therapeutic and biological applications. A better understanding of the identified key-steps, including endocytosis, endosomal escape and nuclear delivery is required for further developments to improve their efficacy. Here, we developed a labelling protocol using aminated nanoparticles as markers for plasmid DNA to examine the intracellular route of lipoplexes in cell lines using transmission electron microscopy. Morphological changes of lipoplexes, membrane reorganizations and endosomal membrane ruptures were observed allowing the understanding of the lipoplex mechanism until the endosomal escape mediated by cationic lipids. The study carried out on two cationic lipids, bis(guanidinium)-tris(2-aminoethyl)amine-cholesterol (BGTC) and dioleyl succinyl paramomycin (DOSP), showed two pathways of endosomal escape that could explain their different transfection efficiencies. For BGTC, a partial or complete dissociation of DNA from cationic lipids occurred before endosomal escape while for DOSP, lipoplexes remained visible within ruptured vesicles suggesting a more direct pathway for DNA release and endosome escape. In addition, the formation of new multilamellar lipid assemblies was noted, which could result from the interaction between cationic lipids and cellular compounds. These results provide new insights into DNA transfer pathways and possible implications of cationic lipids in lipid metabolism

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Synthesis of Orthogonal N -Protected C -Functional Side-Bridged Cyclams to Give Access to Unsymmetrical Constrained BCAs

International audienceConsidering the current importance of unsymmetrical mono- and di-N-functionalized ethylene side-bridged (sb) cyclams and the need to have their C-appended derivatives bearing an additional function dedicated to a conjugation to an external moiety as a targeting biomolecule, we have developed a general procedure to obtain orthogonally N-protected sb‑cyclams with a benzyl or a Boc group. Despite the lack of symmetry of the compounds, this methodology allows the specific protection of one or the other remaining secondary amine function.Compte tenu de l’importance actuelle des cyclams à side-bridged (sb) asymétriques mono- et di-N-fonctionnalisés et de la nécessité d’avoir leurs dérivés C-fonctionnels portant une fonction supplémentaire dédiée à la conjugaison à une entité externe telle qu’une biomolécule de ciblage, nous avons mis au point une procédure générale permettant d’obtenir des cyclams sb N-protégés orthogonalement avec un groupe benzyle ou un groupe Boc. Malgré le manque de symétrie des composés, cette méthodologie permet la protection spécifique de l’une ou l’autre des fonctions amines secondaires restantes

In Vivo Albumin‐Binding of a C ‐Functionalized Cyclam Platform for 64 Cu‐PET/CT Imaging in Breast Cancer Model

International audienceAn improved glucose‐chelator‐albumin bioconjugate (GluCAB) derivative, GluCAB‐2Mal, has been synthesized and studied for in vivo 64Cu‐PET/CT imaging in breast cancer mice models together with its first‐generation analogue GluCAB‐1Mal. The radioligand works on the principle of tumor targeting through the enhanced permeability and retention (EPR) effect with a supportive role played by glucose metabolism. [64Cu]Cu‐GluCAB‐2Mal (99 % RCP) exhibited high serum stability with immediate binding to serum proteins. In vivo experiments for comparison between tumor targeting of [64Cu]Cu‐GluCAB‐2Mal and previous‐generation [64Cu]Cu‐GluCAB‐1Mal encompassed microPET/CT imaging and biodistribution analysis in an allograft E0771 breast cancer mouse model. Tumor uptake of [64Cu]Cu‐GluCAB‐2Mal was clearly evident with twice as much accumulation as compared to its predecessor and a tumor/muscle ratio of up to 5 after 24 h. Further comparison indicated a decrease in liver accumulation for [64Cu]Cu‐Glu‐CAB‐2Mal

Modelling of a 3D Periodic Surface Based on a Folded Resonator Embedded into a Waveguide

International audienceThis paper presents the analysis and modelling of a specific type of three-dimensional frequency-selective surface which unit cells are named as Waveguide Integrated Resonators. This unit cell is identified as a promising structure for broadband filtering applications. An original circuital approach is adopted in order to model this complex volume structure. An equivalent circuit is proposed which reproduces the structure's behaviour under normal incidence. Very good accuracy is obtained within the frequency band of interest, thus validating the proposal

Synthesis of C-functionalized TE1PA and comparison with its analogues. An example of bioconjugation on 9E7.4 mAb for multiple myeloma 64 Cu-PET imaging

International audienceIn view of the excellent copper(ii) and 64-copper(ii) complexation of a TE1PA ligand, a monopicolinate cyclam, in both aqueous medium and in vivo, we looked for a way to make it bifunctional, while maintaining its chelating properties. Overcoming the already known drawback of grafting via its carboxyl group, which is essential to the overall properties of the ligand, a TE1PA bifunctional derivative bearing an additional isothiocyanate coupling function on a carbon atom of the macrocyclic ring was synthesized. This led to an architecture that is comparable to that of other commercially available bifunctional copper(ii) chelators such as p-SCN-Bn-DOTA already used in clinical trials for 64Cu-immuno-PET imaging. The C-functionalization of TE1PA on one carbon atom in the β-N position of the cyclam backbone was successfully achieved by adapting our patented methodology to the huge challenge, allowing the regiospecific mono-N-functionalization of the unsymmetrical ligand. The obtained ligand p-SCN-Bn-TE1PA was coupled to a 9E7.4 murine antibody (mAb), an IgG2a anti CD-138 for multiple myeloma (MM) targeting. The conjugation efficiency was assessed by looking at the 64Cu radiolabeling and the radiopharmaceutical 64Cu-9E7.4-p-SCN-Bn-TE1PA immunoreactivity, and in particular by comparing with 9E7.4-p-SCN-Bn-NOTA and 9E7.4-p-SCN-Bn-DOTA obtained from commercial and presumably highly efficient chelators NOTA and DOTA, respectively. The results are quite clear, showing that p-SCN-Bn-TE1PA has a coupling rate 5 times higher and an immunoreactivity 1.5 to 2 times greater than those of its two competitors. p-SCN-Bn-TE1PA also outperforms TE1PA conjugated via its carboxylic function on the same antibody. The first 64Cu-immuno-PET preclinical study in a syngeneic model of MM was performed, confirming the good in vivo properties of 64Cu-9E7.4-p-SCN-Bn-TE1PA for PET imaging, considering the high clearance even after 24 h and the particularly important tumor-to-liver ratio that was increasing at 48 h