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Hyperpolarization by dissolution dynamic nuclear polarization (dDNP) has enabled promising applications in spectroscopy and imaging, but remains poorly widespread due to experimental complexity. Broad democratization of dDNP could be realized by remote preparation and distribution of hyperpolarized samples from dedicated facilities. Here we show the synthesis of hyperpolarizing polymers (HYPOPs) that can generate radical- and contaminant-free hyperpolarized samples within minutes with lifetimes exceeding hours in the solid state. HYPOPs feature tunable macroporous porosity, with porous volumes up to 80% and concentration of nitroxide radicals grafted in the bulk matrix up to 285 μmol g −1 . Analytes can be efficiently impregnated as aqueous/alcoholic solutions and hyperpolarized up to P ( 13 C) = 25% within 8 min, through the combination of 1 H spin diffusion and 1 H →  13 C cross polarization. Solutions of 13 C-analytes of biological interest hyperpolarized in HYPOPs display a very long solid-state 13 C relaxation times of 5.7 h at 3.8 K, thus prefiguring transportation over long distances. Hyperpolarization by dissolution dynamic nuclear polarization has brought highly sensitive magnetic resonance to reality but there still remains severe limitations. Here the authors show an approach relying on the generation of hyperpolarizing polymers that bear a dual function.

Hyperpolarization by dissolution dynamic nuclear polarization (dDNP) has enabled promising applications in spectroscopy and imaging, but remains poorly widespread due to experimental complexity. Broad democratization of dDNP could be realized by remote preparation and distribution of hyperpolarized samples from dedicated facilities. Here we show the synthesis of hyperpolarizing polymers (HYPOPs) that can generate radical- and contaminant-free hyperpolarized samples within minutes with lifetimes exceeding hours in the solid state. HYPOPs feature tunable macroporous porosity, with porous volumes up to 80% and concentration of nitroxide radicals grafted in the bulk matrix up to 285 μmol g ⁻¹ . Analytes can be efficiently impregnated as aqueous/alcoholic solutions and hyperpolarized up to P( ¹³ C) = 25% within 8 min, through the combination of¹ H spin diffusion and¹ H →¹³ C cross polarization. Solutions of¹³ C-analytes of biological interest hyperpolarized in HYPOPs display a very long solid-state¹³ C relaxation times of 5.7 h at 3.8 K, thus prefiguring transportation over long distances.

NMR-based analysis of metabolite mixtures provides crucial information on biological systems but mostly relies on 1D 1H experiments for maximizing sensitivity. However, strong peak overlap of 1H spectra often is a limitation for the analysis of inherently complex biological mixtures. Dissolution dynamic nuclear polarization (d-DNP) improves NMR sensitivity by several orders of magnitude, which enables 13C NMR-based analysis of metabolites at natural abundance. We have recently demonstrated the successful introduction of d-DNP into a full untargeted metabolomics workflow applied to the study of plant metabolism. Here we describe the systematic optimization of d-DNP experimental settings for experiments at natural 13C abundance and show how the resolution, sensitivity, and ultimately the number of detectable signals improve as a result. We have systematically optimized the parameters involved (in a semi-automated prototype d-DNP system, from sample preparation to signal detection, aiming at providing an optimization guide for potential users of such a system, who may not be experts in instrumental development). The optimization procedure makes it possible to detect previously inaccessible protonated 13C signals of metabolites at natural abundance with at least 4 times improved line shape and a high repeatability compared to a previously reported d-DNP-enhanced untargeted metabolomic study. This extends the application scope of hyperpolarized 13C NMR at natural abundance and paves the way to a more general use of DNP-hyperpolarized NMR in metabolomics studies.

NMR-based analysis of metabolite mixtures provides crucial information on biological systems but mostly relies on 1D 1H experiments for maximizing sensitivity. However, strong peak overlap of1H spectra often is a limitation for the analysis of inherently complex biological mixtures. Dissolution dynamic nuclear polarization (d-DNP) improves NMR sensitivity by several orders of magnitude, which enables 13C NMR-based analysis of metabolites at natural abundance. We have recently demonstrated the successful introduction of d-DNP into a full untargeted metabolomics workflow applied to the study of plant metabolism. Here we describe the systematic optimization of d-DNP experimental settings for experiments at natural 13C abundance and show how the resolution, sensitivity, and ultimately the number of detectable signals improve as a result. We have systematically optimized the parameters involved (in a semi-automated prototype d-DNP system, from sample preparation to signal detection, aiming at providing an optimization guide for potential users of such a system, who may not be experts in instrumental development). The optimization procedure makes it possible to detect previously inaccessible protonated 13C signals of metabolites at natural abundance with at least 4 times improved line shape and a high repeatability compared to a previously reported d-DNP-enhanced untargeted metabolomic study. This extends the application scope of hyperpolarized 13C NMR at natural abundance and paves the way to a more general use of DNP-hyperpolarized NMR in metabolomics studies.

The temporal development of size distributions of diesel exhaust particles and fly ash particles in an enclosed chamber of 1.6 m3 capacity was investigated experimentally and analytically under still conditions (no air movement), stirred conditions (stirred with a fan operating at 2,800 rpm) and ventilated conditions (ventilation rates from 0.448·10-3 s-1 - 4.20· 10-3 s-1 ). Particles were introduced into the chamber, where concentration, mean particle size and distribution shape over time was monitored. Number concentration was measured with a Scanning Mobility Particle Analyzer and a Dustmonitor. Mass concentration was monitored with a Tapered Element Oscillating Microbalance. The generated aerosol concentration was sufficiently high to allow simultaneous coagulation and deposition. The development of size distributions under still conditions was compared with that under stirred conditions and that during ventilation. The particles below 0.05 μm in diameter dropped rapidly below background level under still and stirred conditions, indicating the high susceptibility of the small size range to diffusion controlled processes. Coarse particles larger than 0.5 μm did not decrease in concentration below background level under still conditions. Under stirred conditions their concentration dropped considerably faster than under still conditions and reached levels below background concentration. Experimental results showed that stirring and ventilation enhanced the surface deposition. Heavy particles larger than 0.4 μm in diameter showed an enhanced decay. Coagulation coefficients and deposition velocities regarding mass and number concentration decay were determined from the experimental data by means of nonlinear regression. Determined average coagulation coefficients were in the range of 1.27·10-15 - 2.23·10-15 m3 s-1. No significant difference was found among still, stirred and ventilated conditions. Deposition velocities for paper ash particles and diesel exhaust particles derived from number concentration were 2.07·10-5 and 3.35·10-5 m s-1 under still conditions, 12.7·10-5 and 13.7·10-5 m s-1 under stirred conditions. Ventilated conditions yielded 10.3·10-5 m s-1 for paper ash particles. The mass based deposition velocity of paper ash particles was 3.67·10-5 m s-1 under still conditions, 36.4·10-5 m s-1 under stirred conditions and 37.7·10-5 m s-1 under ventilated conditions. The number concentration based deposition velocities were significantly different among still, stirred and ventilated conditions. Also, the two types of particles were not significantly different in terms of coagulation coefficient or deposition velocity. Experimentally determined coagulation coefficients for a size distribution were higher than Brownian coagulation coefficients, which was attributed to electrostatic charges on the particles, causing mutual attraction by opposite charges. The analytical study combined two existing models, one for deposition and the other for coagulation, and established an algorithm to simulate the two processes simultaneously. Two different diameter definitions were used to calculate deposition and coagulation; the hydrodynamic diameter and the geometric diameter respectively. The analytical investigation showed very good agreement of simulated values with experimental data on the temporal change of concentration and geometric mean diameter of size distributions under still conditions and stirred conditions. The agreement was within 15 % for the temporal change of total concentration, within 5 % for the geometric mean diameter and within 10 % for the change of the lognormal distributions under both still and stirred conditions. The influence of the mass fractal dimension, electrostatic particle charge and turbulence level on concentration and particle size was elaborated. The simulations confirmed that the assumption of diffusion alone is not sufficient to account for the coagulation and deposition, and that the effect of particle charge must be taken into consideration.

Kirkwood-Buff (KB) integrals provide a connection between microscopic properties and thermodynamic properties of multicomponent fluids. The estimation of KB integrals using molecular simulations of finite systems requires accounting for finite size effects. In the small system method, properties of finite subvolumes with different sizes embedded in a larger volume can be used to extrapolate to macroscopic thermodynamic properties. KB integrals computed from small subvolumes scale with the inverse size of the system. This scaling was used to find KB integrals in the thermodynamic limit. To reduce numerical inaccuracies that arise from this extrapolation, alternative approaches were considered in this work. Three methods for computing KB integrals in the thermodynamic limit from information of radial distribution functions (RDFs) of finite systems were compared. These methods allowed for the computation of surface effects. KB integrals and surface terms in the thermodynamic limit were computed for Lennard–Jones (LJ) and Weeks–Chandler–Andersen (WCA) fluids. It was found that all three methods converge to the same value. The main differentiating factor was the speed of convergence with system size L. The method that required the smallest size was the one which exploited the scaling of the finite volume KB integral multiplied by L. The relationship between KB integrals and surface effects was studied for a range of densities.

Background Isocitrate dehydrogenase ( IDH)1/2 wildtype (wt) astrocytomas formerly classified as WHO grade II or III have significantly shorter PFS and OS than IDH mutated WHO grade 2 and 3 gliomas leading to a classification as CNS WHO grade 4. It is the aim of this study to evaluate differences in the treatment-related clinical course of these tumors as they are largely unknown. Methods Patients undergoing surgery (between 2016–2019 in six neurosurgical departments) for a histologically diagnosed WHO grade 2–3 IDH1/2-wt astrocytoma were retrospectively reviewed to assess progression free survival (PFS), overall survival (OS), and prognostic factors. Results This multi-center study included 157 patients (mean age 58 years (20–87 years); with 36.9% females). The predominant histology was anaplastic astrocytoma WHO grade 3 (78.3%), followed by diffuse astrocytoma WHO grade 2 (21.7%). Gross total resection (GTR) was achieved in 37.6%, subtotal resection (STR) in 28.7%, and biopsy was performed in 33.8%. The median PFS (12.5 months) and OS (27.0 months) did not differ between WHO grades. Both, GTR and STR significantly increased PFS (P < 0.01) and OS (P < 0.001) compared to biopsy. Treatment according to Stupp protocol was not associated with longer OS or PFS compared to chemotherapy or radiotherapy alone. EGFR amplification (P = 0.014) and TERT-promotor mutation (P = 0.042) were associated with shortened OS. MGMT-promoter methylation had no influence on treatment response. Conclusions WHO grade 2 and 3 IDH1/2 wt astrocytomas, treated according to the same treatment protocols, have a similar OS. Age, extent of resection, and strong EGFR expression were the most important treatment related prognostic factors.

This protocol describes surgical techniques for long-term intrathecal drug administration to rodent CNS tissue and cerebrospinal fluid collection for monitoring of drug concentration and distribution. Systemic application of therapeutics to the CNS tissue often results in subtherapeutic drug levels, because of restricted and selective penetration through the blood–brain barrier (BBB). Here, we give a detailed description of a standardized technique for intrathecal drug delivery in rodents, analogous to the technique used in humans. The intrathecal drug delivery method bypasses the BBB and thereby offers key advantages over oral or intravenous administration, such as maximized local drug doses with minimal systemic side effects. We describe how to deliver antibodies or drugs over several days or weeks from a s.c. minipump and a fine catheter inserted into the subdural space over the spinal cord (20 min operative time) or into the cisterna magna (10 min operative time). Drug levels can be sampled by quick and minimally invasive cerebrospinal fluid (CSF) collection from the cisterna magna (5 min procedure time). These techniques enable targeted application of any compound to the CNS for therapeutic studies in a wide range of CNS disease rodent models. Basic surgery skills are helpful for carrying out the procedures described in this protocol.

BackgroundVariability in endoscopic assessment necessitates rigorous investigation of descriptors for scoring severity of ulcerative colitis (UC).ObjectiveTo evaluate variation in the overall endoscopic assessment of severity, the intra- and interindividual variation of descriptive terms and to create an Ulcerative Colitis Endoscopic Index of Severity which could be validated.DesignA two-phase study used a library of 670 video sigmoidoscopies from patients with Mayo Clinic scores 0–11, supplemented by 10 videos from five people without UC and five hospitalised patients with acute severe UC. In phase 1, each of 10 investigators viewed 16/24 videos to assess agreement on the Baron score with a central reader and agreed definitions of 10 endoscopic descriptors. In phase 2, each of 30 different investigators rated 25/60 different videos for the descriptors and assessed overall severity on a 0–100 visual analogue scale. κ Statistics tested inter- and intraobserver variability for each descriptor. A general linear mixed regression model based on logit link and β distribution of variance was used to predict overall endoscopic severity from descriptors.ResultsThere was 76% agreement for ‘severe’, but 27% agreement for ‘normal’ appearances between phase I investigators and the central reader. In phase 2, weighted κ values ranged from 0.34 to 0.65 and 0.30 to 0.45 within and between observers for the 10 descriptors. The final model incorporated vascular pattern, (normal/patchy/complete obliteration) bleeding (none/mucosal/luminal mild/luminal moderate or severe), erosions and ulcers (none/erosions/superficial/deep), each with precise definitions, which explained 90% of the variance (pR2, Akaike Information Criterion) in the overall assessment of endoscopic severity, predictions varying from 4 to 93 on a 100-point scale (from normal to worst endoscopic severity).ConclusionThe Ulcerative Colitis Endoscopic Index of Severity accurately predicts overall assessment of endoscopic severity of UC. Validity and responsiveness need further testing before it can be applied as an outcome measure in clinical trials or clinical practice.

We present a low-cost prototype of a visible and near-infrared (VIS-NIR) remote sensing platform, optimized to detect and characterize natural flaming fire fronts from airborne nighttime light (NTL) observations, and its radiometric calibration. It uses commercially available CMOS sensor cameras and filters with roughly 100 nm bandwidths to effectively discriminate burning biomass from other sources of NTL, a critical ability for wildfire monitoring near populated areas. Our filter choice takes advantage of the strong potassium line emission near 770 nm present in natural flaming. The calibrated cameras operate at 20 ms of exposure time and boast radiance measurements with a sensitivity floor, depending on the filter, in the range 3–5 × 10−6 W m−2 sr−1 nm−1 with uncertainties lower than 5% and dynamic ranges near 3000–4000. An additional exposure time with a tenth of the duration is calibrated and extends the dynamic range by a factor of 10. We show images of a spatially resolved fire front from an airborne observation of flaming biomass within this radiance range.