Next generation software for placing atoms into electron density maps

X-ray crystallography is the most common method used to determine the three-dimensional structure of biological macromolecules, with proteins being of particular interest. Both the amplitudes and phases of the diffracted X-ray waves are needed to construct an electron density map, which is then interpreted by building an atomic model. However, the phases cannot be directly measured and must be estimated using either experimental phasing or molecular replacement. BUCCANEER is a program for automatically building protein models into electron density maps, which is iterated in a pipeline with global refinement to refine the model and update the map. The amount of time-consuming manual completion required depends on the success of automated building, which may fail in difficult cases with low resolution data or poorly estimated phases. The aim of this work was to improve automated building and therefore make structure solution quicker and easier. Potential developments to BUCCANEER were explored, but it was changes to the pipeline that proved to be most effective. The pipeline control system was updated and the following steps were added: shift-field refinement, classical density modification, addition of water and dummy atoms, pruning, and final rebuilding of side chains. The new pruning steps delete chains, residues and side chains using two neural networks, which were trained to predict main-chain and side-chain correctness by combining many validation metrics. The set of 54 experimental phasing cases previously used for testing BUCCANEER was expanded to 202 experimental phasing and 1351 molecular replacement cases. The combined pipeline changes substantially improved performance, increasing the mean completeness of the experimental phasing cases from 85% to 91% and the molecular replacement cases from 40% to 74%. The updated pipeline was released as a new program called ModelCraft

The Imprint of Gravitational Waves on the Cosmic Microwave Background

Long-wavelength gravitational waves can induce significant temperature anisotropy in the cosmic microwave background. Distinguishing this from anisotropy induced by energy density fluctuations is critical for testing inflationary cosmology and theories of large-scale structure formation. We describe full radiative transport calculations of the two contributions and show that they differ dramatically at angular scales below a few degrees. We show how anisotropy experiments probing large- and small-angular scales can combine to distinguish the imprint due to gravitational waves.Comment: 11 pages, Penn Preprint-UPR-

ModelCraft : an advanced automated model-building pipeline using Buccaneer

Interactive model building can be a difficult and time-consuming step in the structure-solution process. Automated model-building programs such as Buccaneer often make it quicker and easier by completing most of the model in advance. However, they may fail to do so with low-resolution data or a poor initial model or map. The Buccaneer pipeline is a relatively simple program that iterates Buccaneer with REFMAC to refine the model and update the map. A new pipeline called ModelCraft has been developed that expands on this to include shift-field refinement, machine-learned pruning of incorrect residues, classical density modification, addition of water and dummy atoms, building of nucleic acids and final rebuilding of side chains. Testing was performed on 1180 structures solved by experimental phasing, 1338 structures solved by molecular replacement using homologues and 2030 structures solved by molecular replacement using predicted AlphaFold models. Compared with the previous Buccaneer pipeline, ModelCraft increased the mean completeness of the protein models in the experimental phasing cases from 91% to 95%, the molecular-replacement cases from 50% to 78% and the AlphaFold cases from 82% to 91%

Human Coronary Artery Remodeling, Beginning and End of the Atherosclerotic Process

BACKGROUND, AIMS OF THE STUDY: The objective of the study was to relate the progress of coronary artery remodeling to the earliest stages of the atherosclerotic process. For this purpose, a mathematical model for description of dimensional change of the coronary artery wall and its constituent components was developed and applied. MATERIALS AND METHODS: The study used coronary artery samples randomly taken from each of 83 consecutive, unselected postmortems. All samples were routinely fixed and processed to paraffin for the preparation of right-angled, 5-micron sections, routinely stained and mounted for subsequent analysis. Computer assisted image analysis, using 32 systematic random, radial sampling lines, was used for interactive measurements of distance from centre of lumen to points defining intima, media and adventitia thickness along the radial intercept, which were subsequently tabled for analysis of variance, calculations of (group –vessel) means, and related to stage of pathology. RESULTS: Pre-atherosclerotic changes, before any localised changes in especially intima dimensions, are found, consisting of a process of gradual vascular widening, associated with temporally at least partly dissociated increases in width, which as a fraction of total vessel radius show a phased process. In these, the intima first increases, subsequently remains stable, and finally reduces in width proportionally to the increasing diameter. The media shows a similar initial increase, on average stabilising in the third phase after reaching a plateau value in the second. The adventitia, already increasing in phase 1, continues to increase in phase 2, accelerating in phase 3. The complex process, as found, occurs systematically in all vessels, is distributed circumferentially, and precedes the development of localised lesions of the intima. CONCLUSIONS: The findings suggest the existence of a diffuse complex of changes, consisting of a gradual vascular widening followed by narrowing, with associated mural changes reflecting the atherosclerotic process

Maximum likelihood analysis of systematic errors in interferometric observations of the cosmic microwave background

We investigate the impact of instrumental systematic errors in interferometric measurements of the cosmic microwave background (CMB) temperature and polarization power spectra. We simulate interferometric CMB observations to generate mock visibilities and estimate power spectra using the statistically optimal maximum likelihood technique. We define a quadratic error measure to determine allowable levels of systematic error that do not induce power spectrum errors beyond a given tolerance. As an example, in this study we focus on differential pointing errors. The effects of other systematics can be simulated by this pipeline in a straightforward manner. We find that, in order to accurately recover the underlying B-modes for r=0.01 at 28<l<384, Gaussian-distributed pointing errors must be controlled to 0.7^\circ rms for an interferometer with an antenna configuration similar to QUBIC, in agreement with analytical estimates. Only the statistical uncertainty for 28<l<88 would be changed at ~10% level. With the same instrumental configuration, we find the pointing errors would slightly bias the 2-\sigma upper limit of the tensor-to-scalar ratio r by ~10%. We also show that the impact of pointing errors on the TB and EB measurements is negligibly small.Comment: 10 pages, 4 figures, accepted for publication in ApJS. Includes improvements in clarity of presentation and Fig.4 added, in response to refere

Cosmic Concordance and Quintessence

We present a comprehensive study of the observational constraints on spatially flat cosmological models containing a mixture of matter and quintessence --- a time varying, spatially inhomogeneous component of the energy density of the universe with negative pressure. Our study also includes the limiting case of a cosmological constant. Low red shift constraints include the Hubble parameter, baryon fraction, cluster abundance, age of the universe, bulk velocity and shape of the mass power spectrum; intermediate red shift constraints are due to type 1a supernovae, gravitational lensing, the Ly-a forest, and the evolution of large scale structure; high red shift constraints are based on cosmic microwave background temperature anisotropy. Mindful of systematic errors, we adopt a conservative approach in applying these constraints. We determine that quintessence models in which the matter density parameter is 0.2 \ls \Omega_m \ls 0.5 and the effective, density-averaged equation of state is -1 \le w \ls -0.2, are consistent with the most reliable, current low red shift and CMB observations at the $2\sigma$ level. Factoring in the constraint due to type 1a SNe, the range for the equation of state is reduced to -1 \le w \ls -0.4, where this range represents models consistent with each observational constraint at the 2$\sigma$ level or better (concordance analysis). A combined maximum likelihood analysis suggests a smaller range, -1 \le w \ls -0.6. We find that the best-fit and best-motivated quintessence models lie near $\Omega_m \approx 0.33$, $h \approx 0.65$, and spectral index $n_s=1$, with an effective equation of state $w \approx -0.65$ for ``tracker'' quintessence and $w=-1$ for ``creeper'' quintessence. (abstract shortened)Comment: revised to match ApJ version; 33 pages; 20 figures, 4 in color; uses emulateapj.st

Subaru Hyper Suprime-Cam Survey for An Optical Counterpart of GW170817

We perform a $z$-band survey for an optical counterpart of a binary neutron star coalescence GW170817 with Subaru/Hyper Suprime-Cam. Our untargeted transient search covers $23.6$ deg$^2$ corresponding to the $56.6\%$ credible region of GW170817 and reaches the $50\%$ completeness magnitude of $20.6$ mag on average. As a result, we find 60 candidates of extragalactic transients, including J-GEM17btc (a.k.a. SSS17a/DLT17ck). While J-GEM17btc is associated with NGC 4993 that is firmly located inside the 3D skymap of GW170817, the other 59 candidates do not have distance information in the GLADE v2 catalog or NASA/IPAC Extragalactic Database (NED). Among 59 candidates, 58 are located at the center of extended objects in the Pan-STARRS1 catalog, while one candidate has an offset. We present location, $z$-band apparent magnitude, and time variability of the candidates and evaluate the probabilities that they are located inside of the 3D skymap of GW170817. The probability for J-GEM17btc is $64\%$ being much higher than those for the other 59 candidates ($9.3\times10^{-3}-2.1\times10^{-1}\%$). Furthermore, the possibility, that at least one of the other 59 candidates is located within the 3D skymap, is only $3.2\%$. Therefore, we conclude that J-GEM17btc is the most-likely and distinguished candidate as the optical counterpart of GW170817.Comment: 14 pages, 9 figures. Accepted for publication in PASJ (Publications of the Astronomical Society of Japan

CMB observations from the CBI and VSA: A comparison of coincident maps and parameter estimation methods

We present coincident observations of the Cosmic Microwave Background (CMB) from the Very Small Array (VSA) and Cosmic Background Imager (CBI) telescopes. The consistency of the full datasets is tested in the map plane and the Fourier plane, prior to the usual compression of CMB data into flat bandpowers. Of the three mosaics observed by each group, two are found to be in excellent agreement. In the third mosaic, there is a 2 sigma discrepancy between the correlation of the data and the level expected from Monte Carlo simulations. This is shown to be consistent with increased phase calibration errors on VSA data during summer observations. We also consider the parameter estimation method of each group. The key difference is the use of the variance window function in place of the bandpower window function, an approximation used by the VSA group. A re-evaluation of the VSA parameter estimates, using bandpower windows, shows that the two methods yield consistent results.Comment: 10 pages, 6 figures. Final version. Accepted for publication in MNRA