dataesr/scientific-paragraphs-categorization huggingface dataset:
83 ), and 3D DNA-PAINT superresolution imaging  11, 18  further confirmed the expected dimensions for the particles in solution and revealed that all eight corners of most structures are intact (Fig. 2f  model, Supplementary Figs. 65, 66). To facilitate user-friendly design of large 3D brick structures containing the order of 10 4 components, we developed a software tool called Nanobricks. First, the user draws, imports, or programs (e. g. via mathematical scripting) a 3D shape by placing "voxels" that represent DNA strand domains. The software then converts the shape into associated DNA brick strands. Finally, the software outputs sequences by generating new or applying an existing set of sequences to the strands (Fig. 3a ). The software contains features to add, remove, or modify on the voxel or strand level for each of three steps (Fig.
Design and formation of structures Structures were designed using our Nanobricks software. Depicted 2D strand diagrams were generated from associating caDNAno files. 19 Structures were annealed in 0. 5×TE buffer (5 mM Tris, 1 mM EDTA, pH 8) containing 20 mM MgCl 2 using either an isothermal hold  31  or a narrow annealing ramp. See Supplementary Methods and Supplementary Table  1  for the detailed annealing conditions and optimal temperatures. See supplementary information for sequences used for each structure.
Electron tomography and image processing Samples were deposited on glow-discharged, carbon-coated 300 mesh copper grids and stained using 1% uranyl acetate solution. The grids were then transferred into a JEOL 2200FS FEG transmission microscope using the JEOL high tilt holder. Series of tilted images were collected at a magnification of 50,000 folds by using a 4k × 4k slow-scan CCD camera (Gatan, inc. ) with defocus values of -3 µm and -5 µm. The acquisition was performed semi-automatically using the Serial EM software package. Samples were tilted between -60° and 60° with 2° increment steps. For a detailed description of the alignment and reconstruction procedure see the Supporting Information.
Extended Data Extended Data Figure  1. Gel electrophoresis analysis of DNA brick cuboids Structures were assembled isothermally for 5 -7 days at the temperatures indicated above the lane. The label below a band of interest indicates the gel yield. Extended Data Figure  2. Characterization of 30H×30H×260B cavity shapes a, Schematic depicting the 30H×30H×260B molecular canvas in gray compared with a DNA origami-sized structure in blue. b, For each structure, the top panels show the 3D models of the designed structure. The bottom left panels shows expected TEM projections. The bottom right panels shows TEM averages from at least six particles. c, The structures were folded with 5 nM/strand by annealing isothermally or using a narrow ramp from 52. 5 to 51°C. Products were analyzed on a 0. 5% agarose gel in the presence of 10 mM MgCl 2.
Acknowledgments The authors thank  N. Ponnuswamy ,  R. Sørensen ,  J. Hahn ,  J. Lara ,  L. Chou ,  N. Garreau ,  S. Saka ,  H. Sasaki ,  J. B. Woehrstein , and  C. B. Marks  for experimental help. The authors also thank  B. Wei ,  W. Sun , and  W. M. Shih  for insightful discussions,  M. Beatty  and  J. Cheng  for help in developing the Nanobricks platform, and  C. Chen  for assistance with draft preparation. The work was funded by  Office of Naval Research  grants  N000141010827 ,  N000141310593 ,  N000141410610 , and  N000141612182 , and  N000141612410 , an  Army Research Office  grant  W911NF1210238 ,  National Science Foundation  grants  CCF-1054898 ,  CCF-1162459 ,  CCF-1317291 ,  CMMI-1333215 ,  CMMI-1334109 ,  CMMI-1344915 , an  Air Force Office of Scientific Research  grant  AFA9550-15-1-0514 ,  National Institute of Health  grants  1DP2OD007292  and  1R01EB018659 ,  167814 , (P.
Y. );An  Emory Biomedical Engineering Department Startup Fund , an  Emory Winship Cancer Institute Billi and Bernie Marcus Research Award , an  Winship Cancer Institute  grant # IRG-14-188-0  from the  American Cancer Society , an  National Science Foundation CAREER  Award  DMR-1654485  (Y. K. );  French National Research Agency  grants  ANR-16-CE09-0004-01 ,  ANR-15-CE09-0003-02  (G. B. ); an  French National Research Agency  grant  ANR-10-INBS-05  (P. B. ). L. L. O. was funded by an  NSF  graduate research fellowship. N. H. was funded by the  German National Academic Foundation  and  German Academic Exchange Service. M. T. S. acknowledges support from the  International Max Planck Research School for Molecular and Cellular Life Sciences (IMPRS-LS).
A European project was undertaken to improve the available SOL ICRF physics simulation tools and confront them with measurements. This paper first reviews code upgrades within the project. Using the multi-physics finite element solver COMSOL, the SSWICH code couples RF full-wave propagation with DC plasma biasing over "antenna-scale" 2D (toroidal/radial) domains, via non-linear RF and DC sheath boundary conditions (SBCs) applied at shaped plasma-facing boundaries. For the different modules and associated SBCs, more elaborate basic research in RF-sheath physics, SOL turbulent transport and applied mathematics, generally over smaller spatial scales, guides code improvement. The available simulation tools were applied to interpret experimental observations on various tokamaks. We focus on robust qualitative results common to several devices: the spatial distribution of RF-induced DC bias; left-right asymmetries over strap power unbalance; parametric dependence and antenna electrical tuning; DC SOL biasing far from the antennas, and RF-induced density modifications.
propagation for E and DC SOL biasing for V DC via nonlinear sheath electrical properties. In Europe, these are implemented in the Self-consistent Sheaths and Waves for Ion Cyclotron Heating (SSWICH) code  [1] ,  [2] ,  [3] , using the Newton-Raphson scheme in the multiphysics solver COMSOL. As an intermediate step the code also computes the complex oscillating voltages V RF at sheath boundaries. Rectification likely generates harmonics of the wave frequency  0 but these are neglected in our modelling. We examine below the different modules successively. In several key areas, more elaborate basic research in physics and applied mathematics, generally over smaller spatial scales, guides code improvement.
RF and DC sheath boundary conditions. In "antenna-scale" modelling, limited spatial resolution presently imposes treating the sheaths as non-linear sheath boundary conditions (SBCs) at plasma/sheath interfaces, applied at plasma-facing material boundaries. SSWICH presently incorporates simple RF and DC SBCs. DC SBCs in the DC biasing module reflect the rectifying properties of the sheaths. Current-voltage (j/V) characteristics of sheaths are generally non-linear. Consider for simplicity the case of a static sheath       e f kT V V e j j / exp 1      (1) With T e the electron temperature, V f the floating potential in the absence of RF sheaths, and j + the ion saturation current. When the confinement magnetic field B 0 is tilted by angle  with respect to the wall, j+ is supposed to scale as sin()  [3].
RF wave propagation module for tokamaks RF wave propagation is solved using the Finite Element Method (FEM) to allow versatile wall shapes and plasma in contact with material boundaries for sheath excitation. The original SSWICH-SW version solves for the scalar field E // representing the time harmonic cold SW  [2] 0 // 2 0 // // // //             k E E (9) With k 0 = 0 /c and ( // ,   ) the cold-plasma dielectric constants  [12]. Walls are either parallel or normal to B 0. Excitation is provided by a map of E // from an external antenna code, and prescribed at the antenna mouth (see Figure  1 ). Both fully coupled versions and asymptotic RF-SBCs exist, in a 2D (radial, toroidal) plane. Within the project SSWICH was upgraded to fullwave polarization to solve the vectorial wave equation 0 2 0       εE E k ( 10 ) excited either by straps or vectorial input field maps (see Figure  1 ).
A 2D version was tested in  [3]  including shaped walls and magnetized RF sheaths. Eq. (  6 ) was used to integrate V RF along the curved 1D boundary, assuming V RF =0 far from the antenna. A standalone 3D version of SSWICH-FW with metallic BCs and embedded antenna was developed as RAPLICASOL  [13]. It is presently used as an antenna code in  [14] ,  [15]. An iterative solver (GM-RES) reduces the huge RAM requirements of 3D computations. Figure  1  sketches the simulation domain for the RF module of SSWICH-FW. Focus is put on the antenna vicinity at the Low Field Side (LFS) of a straightened tokamak and does not cover the whole radial and toroidal extension of the vessel. It cannot investigate RFsheaths likely present at the high-field side (HFS). The magnetic connection lengths at LFS are also reduced compared to reality.
In order to fairly reproduce the power coupling in presence of inhomogeneous plasma, the radial extent of the simulation domain needs to include all the relevant R-cutoffs in the radiated k // spectrum. Fig. 1. Sketch of 2D (toroidal/radial) simulation domain for the RF wave module of SSWICH-FW in tokamaks (not to scale). Confinement magnetic field B 0 includes in-plane (B tor ) and out-of-plane (B pol ) components (see Figure  3 ). Colour intensities are indicative of plasma local density. RF waves are excited either by prescribed RF currents on poloidal straps or prescribed RF electric field tangent to the magenta boundary (cut through "antenna aperture" on Figure  3 ). RF SBCs are implemented at blue boundaries. Orange line: cut through "reference plane" on Figure  3. At the inner part of the domain, SSWICH-FW and RAPLICASOL emulate radiation to infinity using Perfectly Matched Layers (PMLs).
DC plasma biasing module of SSWICH The DC plasma biasing module of SSWICH solves the conservation of DC charge over the SOL. div(j DC )=0  (11)  At the separatrix the plasma is supposed to be floating. DC SBCs implement j DC /V DC characteristics (2) with artificial DC wall bias V b (3) driving enhanced DC plasma potentials V DC. In the volume the conduction is supposed to follow a highly anisotropic Ohm's law DC DC DC V σ j    (12) In the parallel direction the Spitzer DC conductivity is taken, while a phenomenological conductivity is introduced transverse to B 0. In references  [2]  and  [15]  typical quantitative values in the range  DC ~10 -6  //DC in the antenna private SOL and  DC ~10 -8  //DC in the main SOL were found to reasonably fit the measurements. Relation (  12 ) is strictly valid only for charged particles colliding with neutrals.
This process is however quite weak in the tokamak SOL. The transverse transport of DC current is more likely turbulent, but SSWICH cannot afford modelling it. Therefore  DC is a loosely constrained parameter. The above DC current transport process was assessed numerically against 3D SOL turbulence simulations using the TOKAM3X fluid code  [27]. As a proxy to the self-biasing by sheath rectification, a local DC bias was imposed on material boundaries protruding into the outer half of the SOL, similar to the antenna side limiters on Figure  1. From these biased wall elements, the DC potential spread along connected magnetic flux tubes over long distances, with parallel attenuation of the peaks and broadening to adjacent field lines. An Ohm's law like  (12)  was found inadequate to describe the local transverse conduction.
The DC plasma biasing module allowing DC current transport is a specificity of SSWICH. Its necessity will be further discussed in the context of tokamak experiments. All alternative codes implicitly assume that the sheaths float over time-scales much longer than the RF period, so that no DC current crosses them. The local DC potential V DC at one sheath then depends only on the local V RF. It is independent of the sheaths at the opposite extremity of the same field line or on neighbouring flux tubes. The SSWICH-SW code was applied for the first time in 2012 to interpret observations on Tore Supra (TS)  [2]. Predictions were also made for WEST and ITER  [30]. The project revisited the TS simulations with the upgraded SSWICH-FW tool  [3] , and extended the tokamak database to ASDEX upgrade (AUG) 2-strap and 3-strap antennas  [14] ,  [15]  as well as JET ITER-like Antenna (ILA)  [31].
Mostly run was the SSWICH-SW version using asymptotic RF-SBCs (  7 ) and (  8 ), with no attempt at selfconsistency. The fully-coupled SSWICH-SW version was run in a few TS cases, showing that the asymptotic approximation, corresponding to the first turn around the self-consistent loop, was a fair approximation of the final result in these cases  [2]. In  [3]  the TS simulations were also revisited using the SSWICH-FW code with asymptotic RF-SBCs. Specific effects related to the Fast Wave were investigated. In all cases a multi-2D procedure was followed and is sketched on Figure  3  for SSWICH-FW: using 2D (toroidal/poloidal) input field maps from 3D antenna codes with plasma load but without sheaths (either TOPICA  [32]  or RAPLICASOL  [13] ), independent 2D (radial/toroidal) simulations were performed at each altitude along the antenna mouth, assuming negligible poloidal gradients.
For SSWICH-SW simulations, this multi-2D procedure was assessed in  [33] : it is valid as long as the input RF field maps do not exhibit small-scale poloidal structures below the electron skin depth c/ pe. The multi-2D approach will be further discussed below for Fast Wave propagation. Fig. 3. 3D sketch of multi-2D simulation procedure with SSWICH-FW code excited using antenna codes. Independent 2D runs are successively performed in each (toroidal/radial) simulation plane, detailed on Figure  1  and visualized here from plasma side. They take as excitation poloidal cuts through a 2D (toroidal/poloidal) input field map prescribed at antenna aperture. From the simulation output, V DC is mapped in section 3. 1 in the orange (radial/poloidal) reference plane. Quantitative sensitivity of the simulations on loosely constrained parameters is frequently reported  [20] ,  [15] ,  [2].
For TS, 2D (radial/poloidal) maps of V DC were also produced using the SSWICH-FW asymptotic code  [3]. In order to evidence a possible role of the Fast Wave, the code was run using either E // only (dominant SW) or E poloidal only (dominant Fast Wave), or their combination in the vectorial input field map from RAPLICASOL. The experimental poloidal distribution of V DC was best reproduced with SW only. Even in the antenna vicinity the presence of the Fast Wave changed V RF and V DC magnitudes and poloidal shapes: contrary to experiments, small-scale poloidal modulations appeared in the simulations, correlated with the poloidal spacing of FS bars. It is suspected that the multi-2D approach over-estimates these poloidal modulations: it underestimates the Fast Wave radial evanescence for large poloidal wavenumbers.
Another perspective to interpret the experiments in relation with antenna geometry, is to consider the SSWICH-SW code excited by a prescribed E // field map, still assuming fixed sheath widths  [33]. The linearity of the RF model then implies that V RF (r) can be reexpressed formally as a linear combination of individual contributions by every emitting point in the field map.       0 0 0 dr r r, r r G E V aperture RF   // (16) Expression (  16 ) is a weighted integral of E // and replaces the line integral Ṽ=E //. dl often used to assess RF sheaths. Symmetry arguments imply G(x,-z,z 0 )=G(x,z,z 0 ) for toroidally opposite limiters. SW evanescence makes individual weights G(r,r 0 ) all the larger as the wave emission point r 0 is located closer to the observation point r, both in the parallel and transverse directions.
This experiment was simulated using the SSWICH-SW asymptotic code  [14] ,  [15]. Over the parametric scan, a local minimum of the simulated V DC was obtained for electrical settings close to the experimental optimum. The minimal V DC for the 3-strap antenna was significantly smaller than the one for the 2strap antenna at the same power on the same plasma. On the RAPLICASOL input field map, the optimal setting corresponded to low values of the local E // near the antenna frame, consistent with expected spatial proximity effects. Yet, complete sheath cancellation could not be achieved simultaneously everywhere over the 3-strap antenna structure: a residual RF-induced DC bias still persisted even with the optimal RF setting.
Spatially inhomogeneous SOL density modifications were measured in several devices during ICRH, e. g. in  [46] ,  [47] ,  [48]. Local RF-induced density E DC ×B 0 convection is suspected in the intense DC field E DC =-  V DC. The density changes in turn alter the RF wave propagation and subsequent sheath rectification. To model this process self-consistently for AUG antennas, the SSWICH-SW asymptotic code was iterated with RAPLICASOL and EMC3-EIRENE 3D SOL code for density transport  [18] ,  [19]. In EMC3, V DC was assumed homogeneous along the open field lines. The obtained self-consistent density patterns were compared with local measurements from reflectometers embedded in the AUG 3-strap antenna, showing reasonable agreement.
In the prospect of quantitative prediction, further improvement is needed from more basic research into RF-sheath physics, SOL turbulence and applied mathematics. In its simplest form the SSWICH code gets now widely used in Europe. Despite its relative simplicity, it was already able to reproduce qualitative experimental observations: the poloidal distributions of RF-induced near-field PSI over many antenna configurations; the radial position of V DC peaks; left-right asymmetries upon strap power unbalance; electrical tuning of various antennas; spread of DC bias over long parallel distances and DC current flows. Earlier models, e. g. the oscillating double probe analogy with line integral Ṽ=E //. dl, failed to interpret some of these observations. From these studies, some key physical ingredients have emerged as essential to reproduce the measurement results: accurate input RF field maps from 3D antenna codes; spatial proximity effects in the near field due to SW and possibly fast wave evanescence; parallel and transverse DC current transport.
Moreover, PBS treated for 5 min with He-O 2 CAPP prevents the drop in mitochondrial membrane potential. The inactivation of cancer cells by electrochemical means has been well characterized  39  and involves different mechanisms such as changes in the plasma membrane potential. These changes in plasma -measured in the PAL). Mitochondrial membrane potential was measured using JC-1 by flow cytometry 24 hr post treatment and expressed as a percent of cells with a normal membrane potential. The data shown is representative of three separate cultures. (B) For the same CAPP treatment, rate of superoxide production was measured in HaCaT cells by flow cytometry using MitoSox. Antimycin (4 μ g/ml) and oligomycin (1 μ g/ml) induced a significant increase in mitochondrial ROS (mROS) production and were used as positive controls.
To assess the effects of total membrane disruption oubain 10 nM or 10 μ M valinomycin was added to the cell culture medium. MATLAB software was used to calculate pixel intensities. Measurement of intra-cellular pH. Cytosolic pH after CAPP treatment was measured using pHrodo ™ Green AM with an Intracellular pH Calibration Buffer Kit (Thermofischer, Saint Aubin, France). Briefly, cells were incubated with 10 μ M pHrodo ™ Green AM for 30 min at 37 °C. A standard pH curve was produced using different buffer solutions. Intracellular pH vs. relative fluorescence units was plotted using a microplate fluorimetric reader (BMG-FLUOstar Galaxy, Stuttgart, Germany), excitation/emission wavelengths were 509/533 nm.
Acknowledgements This work has been supported by the  French ANR  project  Plasmaregen. Marlene Dezest  is a recipient of a fellowship from  French Ministere de l'Education Nationale de la Recherche et de Technologie (MENRT). This work was also supported in part by the  Région Midi-Pyrénées, European funds (Fonds Européens de Développement Régional, FEDER) ,  Toulouse Métropole , and the  French Ministry  of research with the  Investissement d' Avenir Program ,  Infrastructures Nationales en Biologie et Santé (ProFI ,  Proteomics French Infrastructure  project,  ANR-10-INBS-08 ) to OBS. Our thanks to  Conseil Régional d' Aquitaine  for the funding of the Aquitraces facility and to  Rosie Cox  for improving the English. Our thanks to Oxiproteomics,  Paris France  for Oxi-map analysis.
The clinical management of these patients is further complicated by a higher prevalence of comorbidities, including hyperlipidemia, cardiovascular disease, cancer, and diabetes. 12 The benefits of immediate ART initiation might be partially or totally offset by polypharmacy, ie, taking a large number of different medicines,  13  that can make adherence to ART more difficult and can increase the risk of drug toxicities and drug interactions. 14  is therefore important to quantify the impact of immediate ART initiation in patients who enter into HIV care at older age. Here we estimate the 5-year risk of all-cause mortality and non-AIDS mortality among ART-naive, AIDS-free individuals aged between 50 and 70 years using data from the HIV-CAUSAL Collaboration of HIV cohorts from Europe and the Americas.
Selection of Patients We included individuals aged between 50 and 70 years, who had at least 1 CD4 cell count and 1 HIV-RNA measured within 3 months of each other, whereas ART-naive and AIDSfree after December 31, 2004. Baseline was defined as the earliest of the date when all the inclusion criteria were met. Individuals older than 70 years at baseline were rare in our cohorts and were not included because their clinical management might be different due to a higher burden of comorbidities. We considered 2 populations with different background mortality: HIV-positive patients from the general population and US Veterans known to have higher mortality. 15 Individuals from the general HIV population were enrolled in the following cohorts: AMACS (Greece), ANRS CO3 Aquitaine, French Hospital Database, PRIMO, SEROCO (France), ATHENA (the Netherlands), CoRIS, GEMES, PISCIS (Spain), IPEC (Brazil), Southern Alberta Clinic Cohort (Canada), Swiss HIV Cohort study (Switzerland), UK CHIC, and the UK Register of Seroconverters (United Kingdom).
ART Initiation Strategies ART was defined as a combination of antiretroviral drugs including at least 2 nucleoside reverse transcriptase inhibitors plus either 1 or more protease inhibitors, 1 nonnucleoside reverse transcriptase inhibitor, 1 entry/fusion inhibitor, or 1 integrase inhibitor. For each population, we estimated the 5-year risk of allcause mortality and non-AIDS mortality if all participants had started ART within 3 months of baseline (immediate ART initiation). We compared these estimates with those estimated under ART initiation within 3 months of AIDS diagnosis or CD4 count (1) ,500 and (2) ,350 cells/mm 3 , the ART initiation strategies recommended in different settings before the changes in guidelines. We did not account for episodes of ART discontinuation and we assumed that once ART was started, patterns of treatment discontinuation were the same as in the observed data for each of the 2 populations.
Outcomes The outcomes, which were analyzed separately, were allcause mortality and non-AIDS mortality up to 5 years after baseline. For each ART initiation strategy and outcome, we estimated the 5-year risk and risk difference. Non-AIDS mortality was defined as any known cause of death other than AIDS-defining conditions. 16 Cause of death was based on the International Classification of Diseases 10th Revision (ICD-10) and formatted according to CODE (http://www. hicdep. org/). Two cohorts, UK CHIC and IPEC, did not provide data on cause of death and were excluded from the non-AIDS mortality analyses. For all cohorts, death ascertainment and cause of death were based on hospital records and cross-matching with national and local registries. 15.