Simple, reliable protocol for high-yield solubilization of seedless amyloid-β monomer

Self-assembly of the amyloid-β (Aβ) peptide to form toxic oligomers and fibrils is a key causal event in the onset of Alzheimer’s disease, and Aβ is the focus of intense research in neuroscience, biophysics, and structural biology aimed at therapeutic development. Due to its rapid self-assembly and extreme sensitivity to aggregation conditions, preparation of seedless, reproducible Aβ solutions is highly challenging, and there are serious ongoing issues with consistency in the literature. In this paper, we use a liquid-phase separation technique, asymmetric flow field-flow fractionation with multiangle light scattering (AF4-MALS), to develop and validate a simple, effective, economical method for re-solubilization and quality control of purified, lyophilized Aβ samples. Our findings were obtained with recombinant peptide but are physicochemical in nature and thus highly relevant to synthetic peptide. We show that much of the variability in the literature stems from the inability of overly mild solvent treatments to produce consistently monomeric preparations and is rectified by a protocol involving high-pH (>12) dissolution, sonication, and rapid freezing to prevent modification. Aβ treated in this manner is chemically stable, can be stored over long timescales at −80 °C, and exhibits remarkably consistent self-assembly behavior when returned to near-neutral pH. These preparations are highly monomeric, seedless, and do not require additional rounds of size exclusion, eliminating the need for this costly procedure and increasing the flexibility of use. We propose that our improved protocol is the simplest, fastest, and most effective way to solubilize Aβ from diverse sources for sensitive self-assembly and toxicity assays

Filamentary structures of ionized gas in Cygnus X

Interstellar matter and star formatio

Highly-parallelized simulation of a pixelated LArTPC on a GPU

The rapid development of general-purpose computing on graphics processing units (GPGPU) is allowing the implementation of highly-parallelized Monte Carlo simulation chains for particle physics experiments. This technique is particularly suitable for the simulation of a pixelated charge readout for time projection chambers, given the large number of channels that this technology employs. Here we present the first implementation of a full microphysical simulator of a liquid argon time projection chamber (LArTPC) equipped with light readout and pixelated charge readout, developed for the DUNE Near Detector. The software is implemented with an end-to-end set of GPU-optimized algorithms. The algorithms have been written in Python and translated into CUDA kernels using Numba, a just-in-time compiler for a subset of Python and NumPy instructions. The GPU implementation achieves a speed up of four orders of magnitude compared with the equivalent CPU version. The simulation of the current induced on 10^3 pixels takes around 1 ms on the GPU, compared with approximately 10 s on the CPU. The results of the simulation are compared against data from a pixel-readout LArTPC prototype

DISCOVERY OF CARBON RADIO RECOMBINATION LINES IN M82

Carbon radio recombination lines (RRLs) at low frequencies (<=500 MHz) trace the cold, diffuse phase of the interstellar medium, which is otherwise difficult to observe. We present the detection of carbon RRLs in absorption in M82 with LOFAR in the frequency range of 48-64 MHz. This is the first extragalactic detection of RRLs from a species other than hydrogen, and below 1 GHz. Since the carbon RRLs are not detected individually, we cross-correlated the observed spectrum with a template spectrum of carbon RRLs to determine a radial velocity of 219 +- 9 km/s . Using this radial velocity, we stack 22 carbon-{\alpha} transitions from quantum levels n = 468-508 to achieve an 8.5 sigma detection. The absorption line profile exhibits a narrow feature with peak optical depth of 0.003 and FWHM of 31 km/s. Closer inspection suggests that the narrow feature is superimposed on a broad, shallow component. The total line profile appears to be correlated with the 21 cm H I line profile reconstructed from H I absorption in the direction of supernova remnants in the nucleus. The narrow width and centroid velocity of the feature suggests that it is associated with the nuclear starburst region. It is therefore likely that the carbon RRLs are associated with cold atomic gas in the direction of the nucleus of M82.Comment: 6 pages, 5 figures, accepted for publication in ApJ

The LOFAR Two-metre Sky Survey. I: Survey description and preliminary data release

The LOFAR Two-metre Sky Survey (LoTSS) is a deep 120–168 MHz imaging survey that will eventually cover the entire northern sky. Each of the 3170 pointings will be observed for 8 h, which, at most declinations, is sufficient to produce ~5″ resolution images with a sensitivity of ~100 μJy/beam and accomplish the main scientific aims of the survey, which are to explore the formation and evolution of massive black holes, galaxies, clusters of galaxies and large-scale structure. Owing to the compact core and long baselines of LOFAR, the images provide excellent sensitivity to both highly extended and compact emission. For legacy value, the data are archived at high spectral and time resolution to facilitate subarcsecond imaging and spectral line studies. In this paper we provide an overview of the LoTSS. We outline the survey strategy, the observational status, the current calibration techniques, a preliminary data release, and the anticipated scientific impact. The preliminary images that we have released were created using a fully automated but direction-independent calibration strategy and are significantly more sensitive than those produced by any existing large-area low-frequency survey. In excess of 44 000 sources are detected in the images that have a resolution of 25″, typical noise levels of less than 0.5 mJy/beam, and cover an area of over 350 square degrees in the region of the HETDEX Spring Field (right ascension 10h45m00s to 15h30m00s and declination 45°00′00″ to 57°00′00″)

The LOFAR Two-metre Sky Survey. I. Survey description and preliminary data release

The LOFAR Two-metre Sky Survey (LoTSS) is a deep 120-168 MHz imaging survey that will eventually cover the entire northern sky. Each of the 3170 pointings will be observed for 8 h, which, at most declinations, is sufficient to produce ~5? resolution images with a sensitivity of ~100 ?Jy/beam and accomplish the main scientific aims of the survey, which are to explore the formation and evolution of massive black holes, galaxies, clusters of galaxies and large-scale structure. Owing to the compact core and long baselines of LOFAR, the images provide excellent sensitivity to both highly extended and compact emission. For legacy value, the data are archived at high spectral and time resolution to facilitate subarcsecond imaging and spectral line studies. In this paper we provide an overview of the LoTSS. We outline the survey strategy, the observational status, the current calibration techniques, a preliminary data release, and the anticipated scientific impact. The preliminary images that we have released were created using a fully automated but direction-independent calibration strategy and are significantly more sensitive than those produced by any existing large-Area low-frequency survey. In excess of 44 000 sources are detected in the images that have a resolution of 25?, typical noise levels of less than 0.5 mJy/beam, and cover an area of over 350 square degrees in the region of the HETDEX Spring Field (right ascension 10h45m00s to 15h30m00s and declination 45°00?00? to 57°00?00?)