Procedure to construct a multi-scale coarse-grained model of DNA-coated colloids from experimental data

We present a quantitative, multi-scale coarse-grained model of DNA coated colloids. The parameters of this model are transferable and are solely based on experimental data. As a test case, we focus on nano-sized colloids carrying single-stranded DNA strands of length comparable to the colloids' size. We show that in this regime, the common theoretical approach of assuming pairwise additivity of the colloidal pair interactions leads to quantitatively and sometimes even qualitatively wrong predictions of the phase behaviour of DNA-grafted colloids. Comparing to experimental data, we find that our coarse-grained model correctly predicts the equilibrium structure and melting temperature of the formed solids. Due to limited experimental information on the persistence length of single-stranded DNA, some quantitative discrepancies are found in the prediction of spatial quantities. With the availability of better experimental data, the present approach provides a path for the rational design of DNA-functionalised building blocks that can self-assemble in complex, three-dimensional structures.Comment: 17 pages, 10 figures; to be published in Soft Matte

Quantitative prediction of the phase diagram of DNA-functionalized nano-colloids

We present a coarse-grained model of DNA-functionalized colloids that is computationally tractable. Importantly, the model parameters are solely based on experimental data. Using this highly simplified model, we can predict the phase behavior of DNA-functionalized nano-colloids without assuming pairwise additivity of the inter-colloidal interactions. Our simulations show that for nano-colloids, the assumption of pairwise additivity leads to substantial errors in the estimate of the free energy of the crystal phase. We compare our results with available experimental data and find that the simulations predict the correct structure of the solid phase and yield a very good estimate of the melting temperature. Current experimental estimates for the contour length and persistence length of single-stranded DNA sequences are subject to relatively large uncertainties. Using the best available estimates, we obtain predictions for the crystal lattice constants that are off by a few percent: this indicates that more accurate experimental data on ssDNA are needed to exploit the full power of our coarse-grained approach.Comment: 4 pages, 2 figures; accepted for publication in Phys. Rev. Let

DNA mechanics as a tool to probe helicase and translocase activity

Helicases and translocases are proteins that use the energy derived from ATP hydrolysis to move along or pump nucleic acid substrates. Single molecule manipulation has proved to be a powerful tool to investigate the mechanochemistry of these motors. Here we first describe the basic mechanical properties of DNA unraveled by single molecule manipulation techniques. Then we demonstrate how the knowledge of these properties has been used to design single molecule assays to address the enzymatic mechanisms of different translocases. We report on four single molecule manipulation systems addressing the mechanism of different helicases using specifically designed DNA substrates: UvrD enzyme activity detection on a stretched nicked DNA molecule, HCV NS3 helicase unwinding of a RNA hairpin under tension, the observation of RecBCD helicase/nuclease forward and backward motion, and T7 gp4 helicase mediated opening of a synthetic DNA replication fork. We then discuss experiments on two dsDNA translocases: the RuvAB motor studied on its natural substrate, the Holliday junction, and the chromosome-segregation motor FtsK, showing its unusual coupling to DNA supercoiling

Modern applications of machine learning in quantum sciences

In these Lecture Notes, we provide a comprehensive introduction to the most recent advances in the application of machine learning methods in quantum sciences. We cover the use of deep learning and kernel methods in supervised, unsupervised, and reinforcement learning algorithms for phase classification, representation of many-body quantum states, quantum feedback control, and quantum circuits optimization. Moreover, we introduce and discuss more specialized topics such as differentiable programming, generative models, statistical approach to machine learning, and quantum machine learning.Comment: 268 pages, 87 figures. Comments and feedback are very welcome. Figures and tex files are available at https://github.com/Shmoo137/Lecture-Note

ECMO for COVID-19 patients in Europe and Israel

Since March 15th, 2020, 177 centres from Europe and Israel have joined the study, routinely reporting on the ECMO support they provide to COVID-19 patients. The mean annual number of cases treated with ECMO in the participating centres before the pandemic (2019) was 55. The number of COVID-19 patients has increased rapidly each week reaching 1531 treated patients as of September 14th. The greatest number of cases has been reported from France (n = 385), UK (n = 193), Germany (n = 176), Spain (n = 166), and Italy (n = 136) .The mean age of treated patients was 52.6 years (range 16–80), 79% were male. The ECMO configuration used was VV in 91% of cases, VA in 5% and other in 4%. The mean PaO2 before ECMO implantation was 65 mmHg. The mean duration of ECMO support thus far has been 18 days and the mean ICU length of stay of these patients was 33 days. As of the 14th September, overall 841 patients have been weaned from ECMO support, 601 died during ECMO support, 71 died after withdrawal of ECMO, 79 are still receiving ECMO support and for 10 patients status n.a. . Our preliminary data suggest that patients placed on ECMO with severe refractory respiratory or cardiac failure secondary to COVID-19 have a reasonable (55%) chance of survival. Further extensive data analysis is expected to provide invaluable information on the demographics, severity of illness, indications and different ECMO management strategies in these patients

Recombinaison Génétique à l'Échelle de la Molécule Unique : Micromécanique des Jonctions de Holliday et Activité du Complexe RuvAB

This work is a study, at the single molecule level, of the recombination intermediate producedwhen two homologous DNA molecules exchange their single-strands : the Holliday junction.First, we show that a negative torque applied on a DNA molecule with an entirely palindromicsequence leads to the formation of a Holliday junction. The strand exchange can then be directly drivenby mechanical torsion. Using this technique we accessed experimentally, and for the first time with sucha precision, to the value in solution of the helical pitch of DNA : 3.61 ± 0.03 nm/tr.We also studied the kinetics of the strand exchange process under the influence of mechanicalconstraints and in the presence of magnesium ions. We then developed a simple model of the mechanicalbehavior of the Holliday junction under mechanical constraint in order to interpret the experimental data.The single-strand exchange can also be catalyzed by specific enzymes. The mechanical workproduced during this activity defines these proteins as molecular motors. The second part of this workconcerns the study, at the single molecule level, of one of these enzymes : the RuvAB complex of thebacteria Escherichia coli.Firstly, we characterized the RuvAB migration activity on single Holliday junctions. In particular,we found that the complex is highly processive and we estimated its speed at 37◦C and in presenceof 1 mM ATP : ∼ 43 base pairs exchanged per second.Furthermore, we have shown that the RuvA subunit alone catalyzes the exchange of base-pairsthat occurs at the branch point of the structure.Ce travail présente tout d'abord l'étude, à l'échelle de la molécule individuelle, de l'intermédiairede recombinaison formé par l'échange de simples brins entre deux molécules d'ADN homologues : lajonction de Holliday.Nous montrons tout d'abord qu'il est possible, à partir d'un ADN portant une séquence entièrementpalindromique, de former une jonction de Holliday en appliquant une torsion négative. Une foisla jonction formée, la torsion permet également de contrôler de façon directe l'échange des simples brins.Cette technique nous a permis d'accéder expérimentalement, avec une très bonne précision, à la valeuren solution du pas hélicoïdal de l'ADN : 3.61 ± 0.03 nm/tr.Ensuite nous avons étudié, en présence d'ions magnésium, la cinétique de migration de la jonctionde Holliday sous l'influence des contraintes mécaniques. Une modélisation simple du comportementde la jonction de Holliday vis-à-vis des contraintes mécaniques a été développée permettant d'expliquerleur influence sur le mécanisme de migration.L'échange des simples brins peut également être catalysé par certaines enzymes. Le travailmécanique développé au cours de cette activité catalytique fait de ces enzymes des moteurs moléculaires.La seconde partie de ce travail porte sur l'étude en molécule unique d'un tel moteur : le complexe RuvABde la bactérie Escherichia coli.Nous avons tout d'abord caractérisé la migration de jonctions de Holliday individuelles sousl'action du complexe RuvAB. Nous avons notamment montré la très grande processivité du complexe etnous avons pu estimer la vitesse de migration à 37◦C et en présence d'1 mM d'ATP : ∼ 43 paires debases échangées par seconde.D'autre part, et pour finir, nous avons mis en évidence le rôle catalytique de la sous-unité RuvAdans l'échange des paires de bases au niveau du point de branchement

Recombinaison génétique à l'échelle de la molécule unique (micromécanique des jonctions de Holliday et activité du complexe RuvAB)

PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Advanced Examination Techniques Applied to the Assessment of Vacuum Pressure Impregnation (VPI) of ITER Correction Coils

The ITER Magnet System includes a set of 18 superconducting correction coils (CC) which are used to compensate the error field modes arising from geometrical deviations caused by manufacturing and assembly tolerances. The turn and ground insulation are electrically insulated with a multi-layer fiberglass polyimide interleaved composite, impregnated with epoxy resin using vacuum pressure impregnation (VPI). Adequate high voltage insulation (5 kV), mechanical strength and rigidity of the winding pack should be achieved after impregnation and curing of the insulation system. VPI is an effective process to avoid defects such dry spots and incomplete wet out. This insulation technology has also been developed since several years for application to large superconducting coils and more recently to ITER CC. It allows the coils to be impregnated without impacting on their functional characteristics. One of the critical challenges associated with the construction of the CC is the qualification of the VPI insulation. Sections issued from representative VPI test samples with real scale side correction Coil (SCC) cross-section have been delivered and characterized at CERN. High resolution micro-optical inspections have been carried out on large areas through digital microscopy. The aim was to identify lack of impregnation, areas of pure resin and void entrapments. The areas near the filling fibre glass rope received special attention. High precision dimensional and geometrical assessments have been performed with the help of image analysis. Compression and pull-out tests have been also carried out. Finally, high-resolution 3D-computed tomography has been applied for a full volumetric inspection of the sections, enabling the reconstruction in three dimensions of the VPI samples and allowing to fully detect, confirm, and image the volume defects already identified by micro-optical observations