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Motivation Long-read phasing has been used for reconstructing diploid genomes, improving variant calling and resolving microbial strains in metagenomics. However, the phasing blocks of existing methods are broken by large Structural Variations (SVs), and the efficiency is unsatisfactory for population-scale phasing. Results This article presents a novel algorithm, LongPhase, which can simultaneously phase single nucleotide polymorphisms (SNPs) and SVs of a human genome in 10–20 min, 10× faster than the state-of-the-art WhatsHap, HapCUT2 and Margin. In particular, co-phasing SNPs and SVs produces much larger haplotype blocks (N50 = 25 Mbp) than those of existing methods (N50 = 10–15 Mbp). We show that LongPhase combined with Nanopore ultra-long reads is a cost-effective and highly contiguous solution, which can produce between one and 26 blocks per chromosome arm without the need for additional trios, chromosome-conformation and strand-seq data. Availabilityand implementation LongPhase is freely available at https://github.com/twolinin/LongPhase/. Supplementary information Supplementary data are available at Bioinformatics online.

NMR spectra acquired with experiments using frequency-sweeps such as the wide-band uniform-rate smooth truncation (WURST) spin-echo and Carr-Purcell-Meiboom-Gill (CPMG) sequences cannot be absorptively phased by using only conventional zeroth- and first-order phase correction. Implementation of phase correction up to the second-order is described for obtaining absorptive spectra, which have more desirable line shapes and noise properties than magnitude spectra. The relationship of the second-order phase to the parameters of frequency sweeps is derived. The second-order phasing in the frequency-domain is equivalent to a point spread in the time-domain signal. The application of second-order phase correction is demonstrated with a wideline 35Cl CPMG spikelet spectrum.

IUCrJ 8(6), 905 - 920 (2021). doi:10.1107/S2052252521008046, Serial femtosecond crystallography (SFX) at X-ray free-electron lasers (XFELs) enables essentially radiation-damage-free macromolecular structure determination using microcrystals that are too small for synchrotron studies. However, SFX experiments often require large amounts of sample in order to collect highly redundant data where some of the many stochastic errors can be averaged out to determine accurate structure-factor amplitudes. In this work, the capability of the Swiss X-ray free-electron laser (SwissFEL) was used to generate large-bandwidth X-ray pulses [$����/��$ = 2.2% full width at half-maximum (FWHM)], which were applied in SFX with the aim of improving the partiality of Bragg spots and thus decreasing sample consumption while maintaining the data quality. Sensitive data-quality indicators such as anomalous signal from native thaumatin micro-crystals and de novo phasing results were used to quantify the benefits of using pink X-ray pulses to obtain accurate structure-factor amplitudes. Compared with data measured using the same setup but using X-ray pulses with typical quasi-monochromatic XFEL bandwidth (����/�� = 0.17% FWHM), up to fourfold reduction in the number of indexed diffraction patterns required to obtain similar data quality was achieved. This novel approach, pink-beam SFX, facilitates the yet underutilized de novo structure determination of challenging proteins at XFELs, thereby opening the door to more scientific breakthroughs., Published by Chester

Many in-band full-duplex (IBFD) applications require omnidirectional radiation coverage in addition to multilayered self-interference cancellation (SIC). While system-level SIC approaches often require high-isolation antennas before implementing analog and/or digital methods, maintaining the desired omnidirectional transmit/receive patterns is difficult for compact designs that utilize the same polarization. This article discusses the concept development and design progression of the circular mode phasing technique applied to omnidirectional IBFD antenna arrays. The theoretical fundamentals are presented along with simulation results and then validated through the discussion of two prototype antennas, which were measured to provide up to 60 dB of isolation over 2.4–2.5 GHz, which is the highest reported for this SIC method. Additionally, the evolution of this concept for a collection of measured prototypes is summarized and characterized with a unique figure of merit, which should help advance the application of this technique within future IBFD systems.

This study focuses on vibration reduction for quadcopters and octocopters with elastic, two-bladed, fixed-speed, variable-pitch rotors through the use of relative rotor phasing. The study defines phase modes such as a pitch phase mode with relative phasing between the front and aft rotors, a roll phase mode with relative phasing between the left and right rotors, and a differential phase mode with relative phasing between the clockwise and counter-clockwise spinning rotors for both the quadcopter and the octocopter, as well as additional higher harmonic phase modes for the octocopter. Parametric studies on individual phase modes indicate that, for the quadcopter in forward flight, the pitch and roll phase modes can almost entirely eliminate the 2/rev vibratory forces (at the aircraft level), but the 2/rev vibratory moments cannot be minimised at the same time. By simultaneously using multiple phase modes, a Pareto front can be generated and a solution selected based on the relative emphasis on force or moment vibration reduction. For the octocopter, it was observed that individual higher harmonic modes (specifically the 2cor 2smodes) could almost entirely eliminate both the 2/rev vibratory forces and moments, simultaneously. Compared with vibration levels in forward flight that might, on average, be expected if the rotors were randomly phased, a 62% reduction of a composite vibration index can be achieved on a quadcopter, and complete elimination of vibration was achievable on an octocopter, with appropriate rotor phasing.

Battery electric vehicles (BEVs) are being integrated into the UK transport network to reduce operating emissions (OEs) as BEVs produce zero emission at point of use. True OEs depend upon fuel source emissions, and ‘cradle-to-grave’ life cycle emissions. This paper investigates method comparisons of a simple operation emissions model (OPEM) against a life cycle analysis (LCA) (Transport Energy and Air Pollution Model (TEAM-UK)) approach to inform on the UK’s target to achieve net zero emissions. Emission comparisons from internal combustion engine vehicles (ICEVs) and BEVs between 2017 and 2050 using TEAM-UK (estimating both OEs and full LCA) and the OPEM (OEs only) across three vehicle scenarios were analysed: (S1) 100% ICEVs, (S2) new ICEVs banned from 2040, and (S3) new ICEVs banned from 2030. Both model outputs varied between scenarios. The OPEM predicted 19% more emissions in S1 (OEs only comparison). Differences between methods in S2 and S3 were minimal (

This paper presents a new global optimal Phasor Measurement Unit (PMU) placement approach based on branch and bound algorithm. The proposed technique provides the global minimum number and locations of PMUs for any power system. Different objective functions are investigated including (i) minimum number and optimum location of PMUs for full observability, and (ii) maximum system observability with specific number of PMUs (PMU Investment phasing). Moreover, the loss of a power system element or a PMU is also considered. The effects of modeling zero-injection buses and using power flow measurements on the quality of the outputs and real-time studies are presented. The proposed technique is applied to the IEEE 14-, 30-, 57- and 118-bus systems using the MATLAB platform. A comparison between the proposed technique and recently published work is held. The proposed method improves the integer linear programming accuracy, shows superiority over other techniques, and reduces the overall cost.

The assessment of CASP models for utility in molecular replacement is a measure of their use in a valuable real-world application. In CASP7, the metric for molecular replacement assessment involved full likelihood-based molecular replacement searches; however, this restricted the assessable targets to crystal structures with only one copy of the target in the asymmetric unit, and to those where the search found the correct pose. In CASP10, full molecular replacement searches were replaced by likelihood-based rigid-body refinement of models superimposed on the target using the LGA algorithm, with the metric being the refined log-likelihood-gain (LLG) score. This enabled multi-copy targets and very poor models to be evaluated, but a significant further issue remained: the requirement of diffraction data for assessment. We introduce here the relative-expected-LLG (reLLG), which is independent of diffraction data. This reLLG is also independent of any crystal form, and can be calculated regardless of the source of the target, be it X-ray, NMR or cryo-EM. We calibrate the reLLG against the LLG for targets in CASP14, showing that it is a robust measure of both model and group ranking. Like the LLG, the reLLG shows that accurate coordinate error estimates add substantial value to predicted models. We find that refinement by CASP groups can often convert an inadequate initial model into a successful MR search model. Consistent with findings from others, we show that the AlphaFold2 models are sufficiently good, and reliably so, to surpass other current model generation strategies for attempting molecular replacement phasing.

Parametric instabilities alongside severe vibration within gear systems are as due to variation in mesh stiffness, the meshing tooth stiffness changes with changes in the number of contact teeth. T...

Genome sequencing projects routinely generate haploid consensus sequences from diploid genomes, which are effectively chimeric sequences with the phase at heterozygous sites resolved at random. The impact of phasing errors on phylogenomic analyses under the multispecies coalescent (MSC) model is largely unknown. Here, we conduct a computer simulation to evaluate the performance of four phase-resolution strategies (the true phase resolution, the diploid analytical integration algorithm which averages over all phase resolutions, computational phase resolution using the program PHASE, and random resolution) on estimation of the species tree and evolutionary parameters in analysis of multilocus genomic data under the MSC model. We found that species tree estimation is robust to phasing errors when species divergences were much older than average coalescent times but may be affected by phasing errors when the species tree is shallow. Estimation of parameters under the MSC model with and without introgression is affected by phasing errors. In particular, random phase resolution causes serious overestimation of population sizes for modern species and biased estimation of cross-species introgression probability. In general, the impact of phasing errors is greater when the mutation rate is higher, the data include more samples per species, and the species tree is shallower with recent divergences. Use of phased sequences inferred by the PHASE program produced small biases in parameter estimates. We analyze two real data sets, one of East Asian brown frogs and another of Rocky Mountains chipmunks, to demonstrate that heterozygote phase-resolution strategies have similar impacts on practical data analyses. We suggest that genome sequencing projects should produce unphased diploid genotype sequences if fully phased data are too challenging to generate, and avoid haploid consensus sequences, which have heterozygous sites phased at random. In case the analytical integration algorithm is computationally unfeasible, computational phasing prior to population genomic analyses is an acceptable alternative. [BPP; introgression; multispecies coalescent; phase; species tree.]

This work creates a framework for solving highly non-linear satellite formation control problems by using model-free policy optimisation deep reinforcement learning (DRL) methods. This work considers, believed to be for the first time, DRL methods, such as advantage actor-critic method (A2C) and proximal policy optimisation (PPO), to solve the example satellite formation problem of propellantless planar phasing of multiple satellites. Three degree-of-freedom simulations, including a novel surrogate propagation model, are used to train the deep reinforcement learning agents. During training, the agents actuated their motion through cross-sectional area changes which altered the environmental accelerations acting on them. The DRL framework designed in this work successfully coordinated three spacecraft to achieve a propellantless planar phasing manoeuvre. This work has created a DRL framework that can be used to solve complex satellite formation flying problems, such as planar phasing of multiple satellites and in doing so provides key insights into achieving optimal and robust formation control using reinforcement learning.

Two modulated structures of the Hyp-1–ANS complex with different unit-cell dimensions and contents were analyzed in (3+1)D superspace, revealing that they are very similar if not the same higher-dimensional structure with a slight shift in the q vector being responsible for the differences observed in 3D space., Two commensurately modulated structures (PDB entries 4n3e and 6sjj) were solved using translational noncrystallographic symmetry (tNCS). The data required the use of large supercells, sevenfold and ninefold, respectively, to properly index the reflections. Commensurately modulated structures can be challenging to solve. Molecular-replacement software such as Phaser can detect tNCS and either handle it automatically or, for more challenging situations, allow the user to enter a tNCS vector, which the software then uses to place the components. Although this approach has been successful in solving these types of challenging structures, it does not make it easy to understand the underlying modulation in the structure or how these two structures are related. An alternate view of this problem is that the atoms and associated parameters are following periodic atomic modulation functions (AMFs) in higher dimensional space, and what is being observed in these supercells are the points where these higher dimensional AMFs intersect physical 3D space. In this case, the two 3D structures, with a sevenfold and a ninefold superstructure, seem to be quite different. However, describing those structures within the higher dimensional superspace approach makes a strong case that they are closely related, as they show very similar AMFs and can be described with one unique (3+1)D structure, i.e. they are two different 3D intersections of the same (3+1)D structure.

Many low-Earth-orbit constellations consist of multiple small satellites that are launched together in batches, and which make use of differential atmospheric drag for subsequent deployment and pha...

The program SHELIXIR represents a simple and efficient tool for routine phase-problem solution using data for experimental phasing by the single-wavelength anomalous dispersion, multiwavelength anomalous dispersion, single isomorphous replacement with anomalous scattering and radiation-damage-induced phasing methods. As indicated in its name, all calculation procedures are performed with the SHELXC/D/E program package. SHELIXIR provides screening for alternative space groups, optimal solvent content, and high- and low-resolution limits. The procedures of SHELXE are parallelized to minimize the computational time. The automation and parallelization of such procedures are suitable for phasing at synchrotron beamlines directly or for finding the optimal parameters for further data processing. A simple graphical interface is designed to make use easier and to increase efficiency during beam time.

Typical numerical solutions to planning problems under time-dependent constraints (like traffic signals) involve searching in time plus state space. We consider a sampled discrete spatial formulation of the vehicle dynamics. This allows us to propose an optimal planning algorithm with much reduced search-space and time complexity, for vehicles moving across signalized intersections with full knowledge of the traffic Signal, Phasing and Timing (SPaT) information. Then we extend these results to partial knowledge by casting the problem as a Markov Decision Process (MDP). The proposed algorithms are demonstrated through numerical simulations that show a five-fold improvement in runtime compared with a standard time-state formulation, while providing comparable improvements in fuel economy with no vehicle dynamic constraints or traffic rules violated.

Purpose: Designing a new T2 preparation (T2-Prep) module in order to simultaneously provide robust fat suppression and efficient T2 preparation without requiring an additional fat suppression module for T2-weighted imaging at 3T. Methods: The tip-down RF pulse of an adiabatic T2 preparation (T2-Prep) module was replaced by a custom-designed RF excitation pulse that induces a phase difference between water and fat, resulting in a simultaneous T2 preparation of water signals and the suppression of fat signals at the end of the module (now called a phaser adiabatic T2-Prep). Using numerical simulations, in vitro and in vivo ECG-triggered navigator gated acquisitions of the human heart, the blood, myocardium and fat signal-to-noise ratio and right coronary artery (RCA) vessel sharpness using this approach were compared against previously published conventional adiabatic T2-Prep approaches Results: Numerical simulations predicted an increased fat suppression bandwidth and decreased sensitivity against transmit magnetic field inhomogeneities using the proposed approach, while preserving the water T2 preparation capabilities. This was confirmed by the tissue signals acquired on the phantom and the in vivo MRA, which show similar blood and myocardium SNR and CNR and significantly reduced fat SNR compared to the other methods tested. As a result, the RCA conspicuity was significantly increased and the motion artifacts were visually decreased. Conclusion: A novel fat-suppressing T2-preparation method was developed and implemented that demonstrated robust fat suppression and increased vessel sharpness compared with conventional techniques, while preserving its T2 preparation capabilities., Comment: 23 pages, 5 figures, submitted to Magnetic Resonance in Medicine

The endgame scenario that was explored in this analysis consisted of the part of the trajectory starting at the last Ganymede flyby and ending at the final Europa approach. The basic design components included computing the phasing for the final Ganymede encounter, computing the required intermediate Europa flybys, determining the required maneuvers to transition between the intermediate resonances, and interfacing with a computed portal prior to the final approach. The JPL optimization software, COSMIC, was used in the ephemeris model to optimize solutions computed in the circular restricted three-body problem and compute bounds on the attainable set of solutions by sweeping various design parameters.

The ability of nanopore sequencing to simultaneously detect modified nucleotides while producing long reads makes it ideal for detecting and phasing allele-specific methylation. However, there is currently no complete software for detecting SNPs, phasing haplotypes, and mapping methylation to these from nanopore sequence data. Here, we present NanoMethPhase, a software tool to phase 5-methylcytosine from nanopore sequencing. We also present SNVoter, which can post-process nanopore SNV calls to improve accuracy in low coverage regions. Together, these tools can accurately detect allele-specific methylation genome-wide using nanopore sequence data with low coverage of about ten-fold redundancy. Supplementary Information The online version contains supplementary material available at 10.1186/s13059-021-02283-5.

Low-coverage whole-genome sequencing followed by imputation has been proposed as a cost-effective genotyping approach for disease and population genetics studies. However, its competitiveness against SNP arrays is undermined because current imputation methods are computationally expensive and unable to leverage large reference panels. Here, we describe a method, GLIMPSE, for phasing and imputation of low-coverage sequencing datasets from modern reference panels. We demonstrate its remarkable performance across different coverages and human populations. GLIMPSE achieves imputation of a genome for less than US$1 in computational cost, considerably outperforming other methods and improving imputation accuracy over the full allele frequency range. As a proof of concept, we show that 1× coverage enables effective gene expression association studies and outperforms dense SNP arrays in rare variant burden tests. Overall, this study illustrates the promising potential of low-coverage imputation and suggests a paradigm shift in the design of future genomic studies. GLIMPSE is a new method for haplotype phasing and genotype imputation of low-coverage sequencing datasets from large reference panels. GLIMPSE shows remarkable performance across different coverages and human populations.

Single-wavelength anomalous dispersion (SAD)-phasing using sulfur as the unique anomalous scatterer is a powerful method to solve the phase problem in protein crystallography. However, it is not yet widely used by non-expert crystallographers. We report here the structure determination of the double stranded RNA binding domain of human dihydrouridine synthase using the sulfur-SAD method and highly redundant data collected at 1.8 ​Å (“off-edge”), at which the estimated overall anomalous signal was 1.08%. High multiplicity data were collected on a single crystal rotated along the ϕ or ω axis at different κ angles, with the primary beam intensity being attenuated from 50% to 95%, compared to data collection at 0.98 ​Å, to reduce radiation damage. SHELXD succeeded to locate 14 out 15 sulfur sites only using the data sets recorded with highest beam attenuation, which provided phases sufficient for structure solving. In an attempt to stimulate the use of sulfur-SAD phasing by a broader community of crystallographers, we describe our experimental strategy together with a compilation of previous successful cases, suggesting that sulfur-SAD phasing should be attempted for determining the de novo structure of any protein with average sulfur content diffracting better than 3 ​Å resolution., Graphical abstract Image 1, Highlights • The structure of a double stranded RNA binding domain was solved using sulfur-SAD. • X-ray diffraction data were collected on a single crystal in multi-orientations. • Beam attenuation and high data multiplicity were crucial for structure determination. • This paper can guide non-expert crystallographers towards successful S-SAD phasing.

The employment of directed acyclic graphs to advance the tracking, control and appraisal of crystallographic phasing strategies is discussed., Crystallographic phasing strategies increasingly require the exploration and ranking of many hypotheses about the number, types and positions of atoms, molecules and/or molecular fragments in the unit cell, each with only a small chance of being correct. Accelerating this move has been improvements in phasing methods, which are now able to extract phase information from the placement of very small fragments of structure, from weak experimental phasing signal or from combinations of molecular replacement and experimental phasing information. Describing phasing in terms of a directed acyclic graph allows graph-management software to track and manage the path to structure solution. The crystallographic software supporting the graph data structure must be strictly modular so that nodes in the graph are efficiently generated by the encapsulated functionality. To this end, the development of new software, Phasertng, which uses directed acyclic graphs natively for input/output, has been initiated. In Phasertng, the codebase of Phaser has been rebuilt, with an emphasis on modularity, on scripting, on speed and on continuing algorithm development. As a first application of phasertng, its advantages are demonstrated in the context of phasertng.xtricorder, a tool to analyse and triage merged data in preparation for molecular replacement or experimental phasing. The description of the phasing strategy with directed acyclic graphs is a generalization that extends beyond the functionality of Phasertng, as it can incorporate results from bioinformatics and other crystallographic tools, and will facilitate multifaceted search strategies, dynamic ranking of alternative search pathways and the exploitation of machine learning to further improve phasing strategies.

The paper presents a novel de-centralized traffic signal controller, achieved using a Nash bargaining game-theoretic framework, that operates a flexible phasing sequence to adapt to dynamic changes in traffic demand levels. The Nash bargaining algorithm is used to optimize the traffic signal timings at each signalized intersection by modeling each phase as a player in a game, where players cooperate to reach a mutually agreeable outcome. The algorithm was implemented in the INTEGRATION microscopic traffic assignment and simulation software and tested on two sample networks. The proposed control approach was compared to the operation of an optimum fixed-time coordinated plan, an actuated controller, a centralized adaptive phase split controller, a decentralized phase split and cycle length controller, and a fully coordinated adaptive phase split, cycle length, and offset optimization controller to evaluate its performance. Testing was initially conducted on an isolated intersection, showing a 77% reduction in queue length, a a 64% reduction in vehicle delay, and a 17% reduction in vehicle emission levels. In addition, the algorithm was tested on an arterial network producing statistically significant reductions in total delay ranging between 36% and 67% and vehicle emission reductions ranging between 6% and 13%.

We propose methods to determine beam-forming excitation phase profiles for arbitrarily oriented arrays of antennas and scatterers, made of arbitrarily polarized elements. Our generalized analytical phasing (GAP) method provides rapid near-optimal phasing, enabling real-time beam steering with high-element-count, and dynamically configured arrays. In addition, we propose a reduced-order numerical phasing (RONP) method that converts an N -dimensional unknown parameter space (the N unknown phases) to a 2-D space (the optimal beam polarization). Though not as fast as the GAP, this method introduces no reduction in phasing accuracy. Both methods are suitable for a wide range of antenna array and metasurface designs.

In a thermoacoustic engine, acoustic impedance plays a key role to improve the system performance. A matching stub is a component which can be applied to adjust the acoustic impedance. In this study, the effect of locations and lengths of the stub was investigated. The travelling wave engine was designed in looped-tube configuration operating at the frequency about 65 Hz. Air was applied as a working medium, operating at atmospheric pressure. The simulations and experiments were carried out to validate the function of the stub. With a variation of the stub length and its position along the looped-tube, the acoustic impedance can be fine-tuned to obtain the travelling wave phasing in the thermoacoustic core and maximum generated acoustic power.

Software Product Lines (SPLs) are rarely developed from scratch. Commonly, they emerge from one product when there is a need to create tailored variants, or from existing variants created in an ad-hoc way once their separated maintenance and evolution become challenging. Despite the vast literature about re-engineering systems into SPLs and related technical approaches, there is a lack of detailed analysis of the process itself and the effort involved. In this paper, we provide and analyze empirical data of the extraction processes of two open source case studies, namely ArgoUML and Phaser. Both cases emerged from the transition of a monolithic system into an SPL. The analysis relies on information mined from the version control history of their respective source-code repositories and the discussion with developers that took part in the process. Unlike previous works that focused mostly on the structural results of the final SPL, the contribution of this study is an in-depth characterization of the processes. With this work, we aimed at providing a deeper understanding of the strategies for SPL extraction and their implications. Our results indicate that the source code changes can range from almost a fourth to over half of the total lines of code. Developers may or may not use branching strategies for feature extraction. Additionally, the problems faced during the extraction process may be due to lack of tool support, complexity on managing feature dependencies and issues with feature constraints. We made publicly available the datasets and the analysis scripts of both case studies to be used as a baseline for extractive SPL adoption research and practice. This research was partially funded by CNPq, grant no. 408356/2018-9; FAPPR, grant no. 51435; and FAPERJ PDR-10 Fellowship 202073/2020. Open access funding provided by Johannes Kepler University Linz