Large Frequency Differences Research Articles

Allele frequency impacts the cross-ancestry portability of gene expression prediction in lymphoblastoid cell lines.

Population-level genetic studies are overwhelmingly biased toward European ancestries. Transferring genetic predictions from European ancestries to other ancestries results in a substantial loss of accuracy. Yet, it remains unclear how much various genetic factors, such as causal effect differences, linkage disequilibrium (LD) differences, or allele frequency differences, contribute to the loss of prediction accuracy across ancestries. In this study, we used gene expression levels in lymphoblastoid cell lines to understand how much each genetic factor contributes to lowered portability of gene expression prediction from European to African ancestries. We found that cis-genetic effects on gene expression are highly similar between European and African individuals. However, we found that allele frequency differences of causal variants have a striking impact on prediction portability. For example, portability is reduced by more than 32% when the causal cis-variant is common (minor allele frequency, MAF >5%) in European samples (training population) but is rarer (MAF <5%) in African samples (prediction population). While large allele frequency differences can decrease portability through increasing LD differences, we also determined that causal allele frequency can significantly impact portability when the impact from LD is substantially controlled. This observation suggests that improving statistical fine-mapping alone does not overcome the loss of portability resulting from differences in causal allele frequency. We conclude that causal cis-eQTL effects are highly similar in European and African individuals, and allele frequency differences have a large impact on the accuracy of gene expression prediction.

Algorithmically detected rain-on-snow flood events in different climate datasets: a case study of the Susquehanna River basin

Abstract. Rain-on-snow (RoS) events in regions of ephemeral snowpack – such as the northeastern United States – can be key drivers of cool-season flooding. We describe an automated algorithm for detecting basin-scale RoS events in gridded climate data by generating an area-averaged time series and then searching for periods of concurrent precipitation, surface runoff, and snowmelt exceeding predefined thresholds. When evaluated using historical data over the Susquehanna River basin (SRB), the technique credibly finds RoS events in published literature and flags events that are followed by anomalously high streamflow as measured by gauge data along the river. When comparing four different datasets representing the same 21-year period, we find large differences in RoS event magnitude and frequency, primarily driven by differences in estimated surface runoff and snowmelt. Using dataset-specific thresholds improves agreement between datasets but does not account for all discrepancies. We show that factors such as meteorological forcing and coupling frequency, as well as choice of land surface model, play roles in how data products capture these compound extremes and suggest care is to be taken when climate datasets are used by stakeholders for operational decision-making.

Experimental and numerical investigation on detection of BVID in CFRP composite plates using vibro-acoustic modulation

ABSTRACT Carbon fibre reinforced plastic (CFRP) composite has gained popularity due to the advantages such as its high strength-to-weight ratio and high corrosion resistance, but susceptibility to barely visible impact damage limits their use in engineering. This study experimentally and numerically investigates the detection of BVID in CFRP composite plates using Vibro-acoustic modulation (VAM) technique. An experimental system of VAM was constructed for measuring sidebands induced by the nonlinear effects of BVID. An integrated finite element (FE) model is developed to further explore the nonlinear interaction between the BVID, low-frequency pump, and high-frequency probe waves. To address this issue of the mesh size and computational time step mismatch caused by the large difference in frequency between the pump and probe waves, a regionally refined mesh was employed at the BVID region. Furthermore, the effects of BVID’s size and depth on the modulation were discussed. Through the Hilbert-Huang Transform (HHT), the amplitude modulation (AM) and frequency modulation (FM) indexes were extracted from the VAM responses to quantitatively characterise the impact damages. The results demonstrate that the MIA index increases steadily with the exciting voltage and damage degree, making it a suitable indicator to accurately assess the impact damage in CFRP composites.

Forecasting stock volatility using time-distance weighting fundamental’s shocks

The effect of low-frequency fundamentals on high-frequency volatility is assumed to be constant over a low-frequency period in the GARCH-MIDAS model, but this is unrealistic, especially for datasets with large differences in sampling frequencies. We propose a new GARCH-MIDAS model, which innovatively employs a time-distance weighted (TDW) function that can generate time-varying shocks to high-frequency volatility from fundamentals within the same low-frequency period. The empirical results for the Chinese stock market show that the GARCH-MIDAS-TDW model outperforms the GARCH-MIDAS model in both in-sample fitting and out-of-sample forecasting performance, and this finding is also robust to the S&P 500 stock index.

Breakdown of phonon band theory in MgO

We present a series of detailed images of the distribution of kinetic energy among frequencies and wave vectors in the bulk of an MgO crystal as it is heated slowly until it melts. These spectra, which are Fourier transforms of mass-weighted velocity-velocity correlation functions calculated from accurate molecular dynamics (MD) simulations, provide a valuable perspective on the growth of thermal disorder in ionic crystals. We use them to explain why the most striking and rapidly progressing departures from a band structure occur among longitudinal optical (LO) modes, which would be the least active modes at low temperature (T) if phonons did not interact. The degradation of the LO band begins, at low T, as an anomalously large broadening of modes near the center of the Brillouin zone (BZ), which gradually spreads towards the BZ boundary. The LO band all but vanishes before the crystal melts, and transverse optical (TO) modes' spectral peaks become so broad that the TO branches no longer appear band-like. Acoustic bands remain relatively well defined until melting of the crystal manifests in the spectra as their sudden disappearance. We argue that, even at high T, the long wavelength acoustic (LWA) phonons of an ionic crystal can remain partially immune to disorder generated by its LO phonons; whereas, even at low T, its LO phonons can be strongly affected by LWA phonons. This is because LO displacements average out in much less than the period of an LWA phonon; whereas during each period of an LO phonon, an LWA phonon appears as a quasistatic perturbation of the crystal, which warps the LO mode's intrinsic electric field. LO phonons are highly sensitive to acoustic warping of their intrinsic fields because their frequencies depend strongly on them: They cause the large frequency difference between LO and TO bands known as . We calculate vibrational spectra from MD trajectories using a method that we show to be classically exact and therefore applicable, with equal validity, to any solid or liquid in any thermal or nonthermal state. By demonstrating its power and generality, we show that it has become possible to go far beyond the reach of perturbation theories and mean-field theories in the study of vibrations in materials. Published by the American Physical Society 2024

Control of laser-plasma instabilities by non-collinear polychromatic light

Normal broadband lasers with collinear polychromatic components have immense potential for mitigating laser plasma instabilities (LPIs). However, the projection complexity of collinear polychromatic light (CPL) is a significant challenge owing to the demand for a large bandwidth and beamlet number. Here, we propose a theoretical LPI model and optical design for non-collinear polychromatic light (NCPL), which has a small angle ∼4∘ and large frequency difference ∼1% between the double-color beamlets. LPI models of the NCPL demonstrate a decoupling threshold for the shared daughter waves under a multibeam configuration. Compared with the CPL, the wavevector couplings of LPIs are further reduced by the introduced angle. Therefore, both the growth rate and saturation level of LPIs are greatly mitigated by using the NCPL. The two- and three-dimensional simulation results indicate that the NCPL reduces the absolute and convective decoupling thresholds of the CPL and is sufficient to effectively mitigate the reflectivity, hot-electron generation, and intensity of cross-beam energy transfer. An optical design for the efficient generation of ultraviolet NCPL has been presented based on the unsaturated optical parametric amplification and non-collinear sum-frequency generation.

Temporal evolution and spectral characteristics of dual field in a double-pumped microcavity

To generate dual combs for various precision measurements, the temporal evolution and spectral characteristics of dual fields in a double-pumped microcavity are investigated. Results show that by using dual orthogonally polarized pumps, the dual fields can be controlled by regulating the two detunings. The coexistence of solitons and Turing patterns, which is equivalent to dual-frequency combs with a large repetition frequency difference, can be excited. Two positive detuning parameters are similar, and two soliton pulses with identical free spectral ranges and different intensities are formed. Moreover, two weaker positive detunings are beneficial for the dual Turing patterns. Furthermore, breathers and multiple pulses can be excited under special conditions. The effects of dispersion and pump intensity on the dual fields are also studied. Dual combs exist in an anomalous dispersion regime and the strong negative dispersion only leads to DC fields. For the pump intensity, with the increase of pumping power, one field experiences breathers and variable multi-pulse in sequence while the other field maintains Turing patterns. The results of this study provide a new approach to excite dual-frequency combs by using a single microcavity.

Improved artificial intelligence discrimination of minor histological populations by supplementing with color-adjusted images

Despite the dedicated research of artificial intelligence (AI) for pathological images, the construction of AI applicable to histopathological tissue subtypes, is limited by insufficient dataset collection owing to disease infrequency. Here, we present a solution involving the addition of supplemental tissue array (TA) images that are adjusted to the tonality of the main data using a cycle-consistent generative adversarial network (CycleGAN) to the training data for rare tissue types. F1 scores of rare tissue types that constitute < 1.2% of the training data were significantly increased by improving recall values after adding color-adjusted TA images constituting < 0.65% of total training patches. The detector also enabled the equivalent discrimination of clinical images from two distinct hospitals and the capability was more increased following color-correction of test data before AI identification (F1 score from 45.2 ± 27.1 to 77.1 ± 10.3, p < 0.01). These methods also classified intraoperative frozen sections, while excessive supplementation paradoxically decreased F1 scores. These results identify strategies for building an AI that preserves the imbalance between training data with large differences in actual disease frequencies, which is important for constructing AI for practical histopathological classification.

Pitfalls and challenges with population assignments of individuals from admixed populations: Applying Genogeographer on Brazilian individuals

The assignment of individuals to a population can be of importance for the identification of mass disaster victims or criminal offenders in the field of forensic genetics. This assignment is based on biostatistical methods that process data of ancestry informative markers (AIMs), which are selected based on large allele frequency differences between the populations of interest.However, population assignments of individuals with an admixed genetic background are challenging. Admixed individuals are genetic mosaics of chromosomal segments from the parental populations, which may lead to ambiguous or no population assignment. This is problematic since admixture events are a substantial part of human history.In this study, we present challenges of interpreting the evidential weight of population assignments. We used Genogeographer for likelihood ratio (LR) calculations and Brazilians as examples of admixed individuals. Brazilians are a very heterogenous population representing a three-way admixture between Native Americans, Europeans, and Africans. Ancestry informative markers were typed in a total of 589 individuals from Brazil using the Precision ID Ancestry Panel. The Brazilians were assigned to six metapopulations (East Asia, Europe, Middle East, North Africa, South-Central Asia, Sub-Saharan Africa) defined in the Genogeographer software and LRs were calculated if the AIM profile was not an outlier in all metapopulations and simulated two-way (1:1) admixtures of the six metapopulations.Population assignments failed for 55% of the samples. These samples had significantly higher genetic contributions from East Asia, South-Central Asia and Sub-Saharan Africa, and significantly lower genetic contributions from Europe. Most of the individuals with population assignments were assigned to the metapopulations of Middle East (58%) or North Africa (36%), followed by Europe (4%), South-Central Asia (1%), and Sub-Saharan Africa (1%). For 8% of the samples, population assignments were only possible when assignments to simulated two-way (1:1) admixtures of the six metapopulations were considered. Most of these individuals were assigned to two-way admixtures of North Africa, South-Central Asia, or Sub-Saharan Africa.Relatively low median likelihood ratios (LRs<1000) were observed when comparing population likelihoods for Europe, Middle East, North Africa, South-Central Asia, or simulated 1:1 admixtures of these metapopulations. Comparisons including East Asian or Sub-Saharan African populations resulted in larger median LRs (LR>1010).The results suggested that the Precision ID Ancestry Panel provided too little information and that additional markers specifically selected for sub-continental differentiation may be required for accurate population assignment of admixed individuals. Furthermore, a Genogeographer database with additional populations including admixed populations would be advantageous for interpretation of admixed AIM profiles. It would likely increase the number of population assignments and illustrate alternatives to the most likely population, which would be valuable information for the case officer when writing the case report.

Synchronization transitions and sensitivity to asymmetry in the bimodal Kuramoto systems with Cauchy noise

We analyze the synchronization dynamics of the thermodynamically large systems of globally coupled phase oscillators under Cauchy noise forcings with a bimodal distribution of frequencies and asymmetry between two distribution components. The systems with the Cauchy noise admit the application of the Ott–Antonsen ansatz, which has allowed us to study analytically synchronization transitions both in the symmetric and asymmetric cases. The dynamics and the transitions between various synchronous and asynchronous regimes are shown to be very sensitive to the asymmetry degree, whereas the scenario of the symmetry breaking is universal and does not depend on the particular way to introduce asymmetry, be it the unequal populations of modes in a bimodal distribution, the phase delay of the Kuramoto–Sakaguchi model, the different values of the coupling constants, or the unequal noise levels in two modes. In particular, we found that even small asymmetry may stabilize the stationary partially synchronized state, and this may happen even for an arbitrarily large frequency difference between two distribution modes (oscillator subgroups). This effect also results in the new type of bistability between two stationary partially synchronized states: one with a large level of global synchronization and synchronization parity between two subgroups and another with lower synchronization where the one subgroup is dominant, having a higher internal (subgroup) synchronization level and enforcing its oscillation frequency on the second subgroup. For the four asymmetry types, the critical values of asymmetry parameters were found analytically above which the bistability between incoherent and partially synchronized states is no longer possible.

Race, Ethnicity, and Pharmacogenomic Variation in the United States and the United Kingdom.

The relevance of race and ethnicity to genetics and medicine has long been a matter of debate. An emerging consensus holds that race and ethnicity are social constructs and thus poor proxies for genetic diversity. The goal of this study was to evaluate the relationship between race, ethnicity, and clinically relevant pharmacogenomic variation in cosmopolitan populations. We studied racially and ethnically diverse cohorts of 65,120 participants from the United States All of Us Research Program (All of Us) and 31,396 participants from the United Kingdom Biobank (UKB). Genome-wide patterns of pharmacogenomic variation-6311 drug response-associated variants for All of Us and 5966 variants for UKB-were analyzed with machine learning classifiers to predict participants' self-identified race and ethnicity. Pharmacogenomic variation predicts race/ethnicity with averages of 92.1% accuracy for All of Us and 94.3% accuracy for UKB. Group-specific prediction accuracies range from 99.0% for the White group in UKB to 92.9% for the Hispanic group in All of Us. Prediction accuracies are substantially lower for individuals who identified with more than one group in All of Us (16.7%) or as Mixed in UKB (70.7%). There are numerous individual pharmacogenomic variants with large allele frequency differences between race/ethnicity groups in both cohorts. Frequency differences for toxicity-associated variants predict hundreds of adverse drug reactions per 1000 treated participants for minority groups in All of Us. Our results indicate that race and ethnicity can be used to stratify pharmacogenomic risk in the US and UK populations and should not be discounted when making treatment decisions. We resolve the contradiction between the results reported here and the orthodoxy of race and ethnicity as non-genetic, social constructs by emphasizing the distinction between global and local patterns of human genetic diversity, and we stress the current and future limitations of race and ethnicity as proxies for pharmacogenomic variation.

A Review of Modeling and Applications of Energy Storage Systems in Power Grids

As the penetration of variable renewable generation increases in power systems, issues, such as grid stiffness, larger frequency deviations, and grid stability, are becoming more relevant, particularly in view of 100% renewable energy networks, which is the future of smart grids. In this context, energy storage systems (ESSs) are proving to be indispensable for facilitating the integration of renewable energy sources (RESs), are being widely deployed in both microgrids and bulk power systems, and thus will be the hallmark of the clean electrical grids of the future. Hence, this article reviews several energy storage technologies that are rapidly evolving to address the RES integration challenge, particularly compressed air energy storage (CAES), flywheels, batteries, and thermal ESSs, and their modeling and applications in power grids. An overview of these ESSs is provided, focusing on new models and applications in microgrids and distribution and transmission grids for grid operation, markets, stability, and control.

Current allele distribution of the human longevity gene APOE in Europe can mainly be explained by ancient admixture.

Variation in apolipoprotein E (APOE) has been shown to have the strongest genetic effect on human longevity. The aim of this study was to unravel the evolutionary history of the three major APOE alleles in Europe by analysing ancient samples up to 12,000 years old. We detected significant allele frequency shifts between populations and over time. Our analyses indicated that selection led to large frequency differences between the earliest European populations (i.e., hunter-gatherers vs. first farmers), possibly due to changes in diet/lifestyle. In contrast, the allele distributions in populations from ~4000 BCE onward can mainly be explained by admixture, suggesting that it also played an important role in shaping current APOE variation. In any case, the resulting allele frequencies strongly influence the predisposition for longevity today, likely as a consequence of past adaptations and demographic processes.

Advances of Research on Dual-Frequency Solid-State Lasers for Synthetic-Wave Absolute-Distance Interferometry.

Frequency-difference-stabilized dual-frequency solid-state lasers with tunable and large frequency difference have become an ideal light source for the high-accuracy absolute-distance interferometric system due to their stable multistage synthetic wavelengths. In this work, the advances in research on oscillation principles and key technologies of the different kinds of dual-frequency solid-state lasers are reviewed, including birefringent dual-frequency solid-state lasers, biaxial and two-cavity dual-frequency solid-state lasers. The system composition, operating principle, and some main experimental results are briefly introduced. Several typical frequency-difference stabilizing systems for dual-frequency solid-state lasers are introduced and analyzed. The main development trends of research on dual-frequency solid-state lasers are predicted.

Influence of IL-28B serum level and gene polymorphism in a sample of Iraqi patients with ankylosing spondylitis

Ankylosing spondylitis (AS) represents one kind of advanced arthritis formed via inflammatory stimuli long-term in the spin‘s joints. Interleukin (IL)-29 (interferon- lambda1(IFN- λ1)), interleukin (IL)-28A (interferon- lambda 2 (IFN- λ2)) and interleukin (IL)-28B (interferon- lambda 3(IFN-λ3)) are three interferon lambda (IFN- λs) molecules that have recently been identified as new members of the IFN family. IL-28B expression in ankylosing spondylitis (AS) is not well understood. 150 male healthy controls ((HC) and 160 males with AS as patients group participated in this study. Serum level and gene polymorphism were assessed using an enzyme-linked immunosorbent assay and Sanger sequencing for IL-28B, respectively. The results showed significantly lower serum IL-28B concentrations in the AS groups in comparison to the HC groups (both p values equal to 0.003). There was a large difference in IL-28B genotype and allele frequency between the two individuals. IL-28B heterozygote genotype CT of rs12979860 SNP exhibits a substantial correlation with AS (P = 0.008). While the genotypes of rs12980275 SNP were not shown any significant correlation with AS. The findings suggest that serum concentration of IL-28B is a potential diagnostic biomarker in patients with AS, and that the heterozygote CT of rs12979860 SNP serves as a potential risk factor for the onset of AS in the Iraqi population.

Genomic divergence of hatchery- and natural-origin Chinook salmon (Oncorhynchus tshawytscha) in two supplemented populations

Captive propagation is widely used for the conservation of imperiled populations. There have been concerns about the genetic effects of such propagation, but few studies have measured this directly at a genomic level. Here, we use moderate-coverage (10X) genome sequences from 80 individuals to evaluate the genomic distribution of variation of several paired groups of Chinook salmon (Oncorhynchus tshawytscha). These include (1) captive- and natural-origin fish separated by at least one generation, (2) fish within the same generation having high fitness in captivity compared to those with high fitness in the wild, and (3) fish listed as different Evolutionarily Significant Units (ESUs) under the US Endangered Species Act. The distribution of variation between high-fitness captive and high-fitness natural fish was nearly identical to that expected from random sampling, indicating that differential selection in the two environments did not create large allele frequency differences within a single generation. In contrast, the samples from distinct ESUs were clearly more divergent than expected by chance, including a peak of divergence near the GREB1L gene on chromosome 28, a gene previously associated with variation in time of return to fresh water. Comparison of hatchery- and natural-origin fish within a population fell between these extremes, but the maximum value of FST was similar to the maximum between ESUs, including a peak of divergence on chromosome 8 near the slc7a2 and pdgfrl genes. These results suggest that efforts at limiting genetic divergence between captive and natural fish in these populations have successfully kept the average divergence low across the genome, but at a small portion of their genomes, hatchery and natural salmon were as distinct as individuals from different ESUs.

Design of Synthetic-Wave Absolute-Distance Interferometric System Using Two-Cavity Dual-Frequency Nd∶YAG Laser with Large Frequency-Difference

Design of Synthetic-Wave Absolute-Distance Interferometric System Using Two-Cavity Dual-Frequency Nd∶YAG Laser with Large Frequency-Difference

Microwave-activated gates between a fluxonium and a transmon qubit

We propose and analyze two types of microwave-activated gates between a fluxonium and a transmon qubit, namely a cross-resonance (CR) and a CPHASE gate. The large frequency difference between a transmon and a fluxonium makes the realization of a two-qubit gate challenging. For a medium-frequency fluxonium qubit, the transmon-fluxonium system allows for a cross-resonance effect mediated by the higher levels of the fluxonium over a wide range of transmon frequencies. This allows one to realize the cross-resonance gate by driving the fluxonium at the transmon frequency, mitigating typical problems of the cross-resonance gate in transmon-transmon chips related to frequency targeting and residual $ZZ$ coupling. However, when the fundamental frequency of the fluxonium enters the low-frequency regime below $100\phantom{\rule{0.16em}{0ex}}\mathrm{MHz}$, the cross-resonance effect decreases leading to long gate times. For this range of parameters, a fast microwave CPHASE gate can be implemented using the higher levels of the fluxonium. In both cases, we perform numerical simulations of the gate showing that a gate fidelity above $99%$ can be obtained with gate times between 100 and $300\phantom{\rule{0.16em}{0ex}}\mathrm{ns}$. Next to a detailed gate analysis, we perform a study of chip yield for a surface code lattice of fluxonia and transmons interacting via the proposed cross-resonance gate. We find a much better yield as compared to a transmon-only architecture with the cross-resonance gate as native two-qubit gate.

Fast magnetic reconnection and driven plasma rotation in reversed central magnetic shear configuration

Numerical calculations have been carried out to study the nonlinear growth of the double tearing mode (DTM) in the reversed central magnetic shear configuration for medium-size tokamak plasma parameters, based on two-fluid equations and large aspect ratio approximation. Three different regimes of the DTM growth are found. (a) annular crash regime, existing for a small distance but a not too large plasma rotation frequency difference between two resonant surfaces. In this regime the plasma pressure between two resonant surfaces is flattened due to the fast magnetic reconnection in tens of microseconds, in agreement with experimental observations. In addition, a large plasma rotation shear is generated around the edge of the pressure flattening region right after the fast magnetic reconnection. (b) Core crash regime, existing for a medium distance and a relatively low rotation frequency difference between two resonant surfaces, in which the plasma pressure is flattened over a large region up to the magnetic axis during the fast magnetic reconnection in tens of microseconds, in agreement with experimental observation too. (c) No crash regime, existing for a sufficiently large distance and/or frequency difference between two resonant surfaces. In this regime the mode grows slowly in the nonlinear phase and saturates at a finite amplitude, causing a local flattening of the plasma pressure at the resonant surface but without fast crashes.

A mode order optimized disk resonator gyroscope considering thermoelastic damping

Mode properties and thermoelastic damping (TED) are crucial for the disk resonator gyroscope (DRG). Most of the DRG structure designs do not involve the mode order adjustment and the compatibility design of mode order optimization and quality factor is more lacking. In this paper, a novel mode order optimized DRG is designed and its mode properties and TED are investigated. Parametric studies are conducted to explore the DRG performance which is closely related to structure shapes and dimensions. The parametric study of the proposed DRG indicates that the operation mode being the first order and having a low frequency, the large frequency difference between the operation mode and parasitic modes and the high thermoelastic quality factor are compatible by selecting appropriate structural dimensions. To further improve the quality factor, masses and slots are applied in the proposed DRG respectively. The results show that TED can be effectively reduced with reasonable mass or slot configurations and meanwhile the DRG maintains favorable mode properties due to the strong stability of mode order optimization of the proposed DRG. In general, the research finding in this paper can be a useful reference for other micromachined gyroscope designs.