Domain Boundaries Research Articles

Deletion of an evolutionarily conserved TAD boundary impacts spermatogenesis in mice

Abstract Spermatogenesis is a complex process that can be disrupted by genetic and epigenetic changes, potentially leading to male infertility. Recent research has rapidly increased the number of protein coding mutations causally linked to impaired spermatogenesis in humans and mice. However, the role of non-coding mutations remains largely unexplored. As a case study to evaluate the effects of non-coding mutations on spermatogenesis, we first identified an evolutionarily conserved topologically associated domain (TAD) boundary near two genes with important roles in mammalian testis function: Dmrtb1 and Lrp8. We then used CRISPR-Cas9 to generate a mouse line where 26 kb of the boundary was removed including a strong and evolutionarily conserved CTCF binding site. ChIP-seq and Hi-C experiments confirmed the removal of the CTCF site and a resulting mild increase in the DNA–DNA interactions across the domain boundary. Mutant mice displayed significant changes in testis gene expression, higher frequency of histological abnormalities, a drop of 47–52% in efficiency of meiosis, a 15–18% reduction in efficiency of spermatogenesis, and consistently, a 12–28% decrease in daily sperm production compared to littermate controls. Despite these quantitative changes in testis function, mutant mice show no significant changes in fertility. This suggests that non-coding deletions affecting testis gene regulation may have smaller effects on fertility compared to coding mutations of the same genes. Our results demonstrate that disruption of a TAD boundary can have a negative impact on sperm production and highlight the importance of considering non-coding mutations in the analysis of patients with male infertility.

Computational Approaches to Compressible Micropolar Fluid Flow in Moving Parallel Plate Configurations

In this paper, we consider the unsteady flow of a compressible micropolar fluid between two moving, thermally isolated parallel plates. The fluid is characterized as viscous and thermally conductive, with polytropic thermodynamic properties. Although the mathematical model is inherently three-dimensional, we assume that the variables depend on only a single spatial dimension, reducing the problem to a one-dimensional formulation. The non-homogeneous boundary conditions representing the movement of the plates lead to moving domain boundaries. The model is formulated in mass Lagrangian coordinates, which leads to a time-invariant domain. This work focuses on numerical simulations of the fluid flow for different configurations. Two computational approaches are used and compared. The first is based on the finite difference method and the second is based on the Faedo–Galerkin method. To apply the Faedo–Galerkin method, the boundary conditions must first be homogenized and the model equations reformulated. On the other hand, in the finite difference method, the non-homogeneous boundary conditions are implemented directly, which reduces the computational complexity of the numerical scheme. In the performed numerical experiments, it was observed that, for the same accuracy, the Faedo–Galerkin method was approximately 40 times more computationally expensive compared to the finite difference method. However, on a dense numerical grid, the finite difference method required a very small time step, which could lead to an accumulation of round-off errors. On the other hand, the Faedo–Galerkin method showed the convergence of the solutions as the number of expansion terms increased, despite the higher computational cost. Comparisons of the obtained results show good agreement between the two approaches, which confirms the consistency and validity of the numerical solutions.

A multi-physical coupling NURBS-based isogeometric analysis for nonlinear electrodynamics of three-directional poroelastic functionally graded circular nanoplate: Introducing deep neural network algorithm for nonlinear electrodynamics problems

For the right design of nanosystems with integrated piezoelectric transducers and materials, it is crucial to understand the electro-mechanical coupling factor. Considering this, this work determines the influence of placement and dimension of piezoelectric patch on the vibrations of circular sandwich sector nanoplate coupled with an electrically layer. The core of the current nanostructure is made of three-directional poroelastic functionally graded material (3D-PFGM). The quasi-3D sinusoidal shear deformation theory (Q-3DSSDT) considering the effect of thickness stretching, compatibility conditions, and Hamilton's principle are coupled with each other regarding discovering the general motion equations and boundary domains related to the circular sector sandwich nanoplate. For considering the size effect, nonlocal quasi-3D sinusoidal strain gradient theory (NQSSGT) by employing both hardening and softening effects is considered. The NURBS-based isogeometric analysis is applied to answer the partial differential coupled equations (PDCE). In addition, the finite element method is implemented for more verification and presenting important outcomes. The novelties of this work are considering the effects of NQSSGT, placement, and dimension of the piezoelectric patch in addition to considering 3D-PFGM of the circular sector sandwich nanoplate. After obtaining the datasets of the mathematics simulation, a deep neural network algorithm is presented to test, train, and validate the presented nonlinear electrodynamics response of the current circular sector sandwich nanoplate. The results of the current nanostructure can be used in related industries of nano-robots and nano-electronic devices for future works. The findings highlight the significant influence of material gradation, poroelastic effects, and piezoelectric coupling on the vibration characteristics, offering valuable insights for the design and optimization of smart materials and structures in microelectromechanical systems (MEMS), sensors, and actuators. This research paves the way for future innovations in the field of advanced functional materials and their applications in high-precision technologies.

Two unrelated distal genes activated by a shared enhancer benefit from localizing inside the same small topological domain.

Enhancers are tissue-specific regulatory DNA elements that can activate transcription of genes over distance. Their target genes most often are located in the same contact domain-chromosomal entities formed by cohesin DNA loop extrusion and typically flanked by CTCF-bound boundaries. Enhancers shared by multiple unrelated genes are underexplored but may be more common than anticipated. Here, we analyzed the interplay between an enhancer and two distal functionally unrelated genes residing at opposite domain boundaries. The enhancer strongly activated their expression and supported their frequent interactions. Cohesin structured the domain and supported their transcription, but the genes did not rely on each other's transcription or show gene competition. Deleting either domain boundary not only extended the contact domain but led to reduced contacts within the original domain and reduction in the expression of both genes. Conversely, by isolating either gene with the enhancer in shorter domains, through insertion of new CTCF boundaries, intradomain contact frequencies increased, and the gene isolated with the enhancer was upregulated. Collectively, this shows that an enhancer can independently activate unrelated distal genes and that long-range gene regulation benefits from operating in small contact domains.

Closing the Circulation Budget

AbstractCirculation budgets can identify physical processes underpinning tropical cyclones, mesoscale convective vortices, and other weather systems where there are interactions across scales. It is unclear, however, how well these budgets close in practice. The present study uses the rapid intensification of Tropical Cyclone Nepartak (2016) as a case study to quantify the practical limitations of calculating circulation budgets using standard reanalyzes and numerical weather model data. First, we evaluate the circulation budget with ERA5. The budget residual can be reduced considerably by including contributions to circulation changes from subgrid‐scale momentum transports, and reduced further with 24‐hr smoothing, which dampens the discontinuous effects of data assimilation. Second, using a high‐resolution Met Office Unified Model simulation, we examine how the choice of the path used (the domain boundary) affects the budget closure. Third, the truncation errors associated with numerical differentiation in time and space are investigated. The circulation budget improves as the model data are analyzed with more frequent time output intervals, and as the output grid spacing decreases. For the tropical convective examples evaluated here, the column mean budget residuals increase by up to 50% as the output intervals increase from 5 min to 3 hr. Errors also increase if the data are regridded to a coarser horizontal grid spacing and when convection straddles the domain boundary. A key result is that the circulation budget need not close for physical inferences made about the circulation and its evolution to be meaningful, thus validating the use of the technique in prior studies.

Genetic variation in IL-4 activated tissue resident macrophages determines strain-specific synergistic responses to LPS epigenetically

How macrophages in the tissue environment integrate multiple stimuli depends on the genetic background of the host, but this is still poorly understood. We investigate IL-4 activation of male C57BL/6 and BALB/c strain specific in vivo tissue-resident macrophages (TRMs) from the peritoneal cavity. C57BL/6 TRMs are more transcriptionally responsive to IL-4 stimulation, with induced genes associated with more super enhancers, induced enhancers, and topologically associating domains (TAD) boundaries. IL-4-directed epigenomic remodeling reveals C57BL/6 specific enrichment of NF-κB, IRF, and STAT motifs. Additionally, IL-4-activated C57BL/6 TRMs demonstrate an augmented synergistic response upon in vitro lipopolysaccharide (LPS) exposure, despite naïve BALB/c TRMs displaying a more robust transcriptional response to LPS. Single-cell RNA sequencing (scRNA-seq) analysis of mixed bone marrow chimeras indicates that transcriptional differences and synergy are cell intrinsic within the same tissue environment. Hence, genetic variation alters IL-4-induced cell intrinsic epigenetic reprogramming resulting in strain specific synergistic responses to LPS exposure.

Mapping the Energy Carrier Diffusion Tensor in Perovskite Semiconductors.

Understanding energy transport in semiconductors is critical for the design of electronic and optoelectronic devices. Semiconductor material properties, such as charge carrier mobility or diffusion length, are commonly measured in bulk crystals and determined using models that describe transport behavior in homogeneous media, where structural boundary effects are minimal. However, most emerging semiconductors exhibit nano- and microscale heterogeneity. Therefore, experimental techniques with high spatial resolution paired with models that capture anisotropy and domain boundary behavior are needed. We develop a diffusion tensor-based framework to analyze experimental photoluminescence (PL) diffusion maps accounting for material nano- and microstructure. Specifically, we quantify both carrier transport and recombination in single crystal and polycrystalline lead halide perovskites by globally fitting diffusion maps with spatial, temporal, and PL intensity data. We reveal a 29% difference in principal diffusion coefficients and alignment between electronically coupled grains for CH3NH3PbI3 polycrystalline films. This framework allows for understanding and optimizing anisotropic energy transport in heterogeneous materials.

Error analysis for the implicit boundary integral method

The implicit boundary integral method (IBIM) provides a framework to construct quadrature rules on regular lattices for integrals over irregular domain boundaries. This work provides a systematic error analysis for IBIMs on uniform Cartesian grids for boundaries with different degrees of regularity. First, it is shown that the quadrature error gains an additional order of d-12 from the curvature for a strongly convex smooth boundary due to the “randomness” in the signed distances. This gain is discounted for degenerated convex surfaces. Then the extension of error estimate to general boundaries under some special circumstances is considered, including how quadrature error depends on the boundary’s local geometry relative to the underlying grid. Bounds on the variance of the quadrature error under random shifts and rotations of the lattices are also derived.

Sex differences in the maximal metabolic steady state of fitness matched women and men.

PURPOSE: We tested the hypothesis that power at maximal metabolic steady state is similar between fitness matched men and women. METHODS: Eighteen participants (9 men, 9 women) performed a cycling graded exercise test for maximal oxygen consumption (V̇O2max). Men and women were matched for V̇O2 max normalized to fat free mass (FFM), which was 50.4±4.7 ml·min-1·kg FFM-1 and 52.1±8.2 ml·min-1·kg FFM-1, respectively (P=0.62). Participants completed a muscle oxygenation (%SmO2) zero-slope prediction trial and a 3-min trial (3MT). The %SmO2 zero-slope trials included three, 5-min cycling bouts (30 sec rest) spanning intensity domains. Linear regression of trial work rate and %SmO2 slope over the final three minutes established the work rate occurring at the predicted zero slope in %SmO2. The 3MT requires all-out cycling, where end test power (ETP) was calculated as the mean power output over the last 30 sec and work above end test power (WEP) as the power-time integral above ETP. RESULTS: Independent of method, mean (±SD) absolute power at the maximal metabolic steady state was similar between fitness matched women and men (P=0.72), yet became higher in women when expressed relative to FFM (P=0.02). V̇O2 at the power associated with %SmO2 zero-slope represented a significantly higher fraction of V̇O2max for women compared to men (P=0.03). CONCLUSION: Normalized WEP (Watts/kg FFM) remained higher in men (P<0.01). Although highly correlated (r=0.88, P<0.01), ETP was ~8% higher than %SmO2 zero-slope power (P=0.03). Compared to fitness matched men, women displayed higher FFM normalized power associated with the heavy-severe exercise domain boundary.

Social Inclusion/Exclusion in Information Systems: A Review and Roadmap for Research

ABSTRACTOver the past four decades, scholars in information systems (IS) have explored the intricacies of social inclusion/exclusion within IS (SI/E in IS). Despite 40 years of investigation, there remains a notable absence of a systematic analysis of the accumulated knowledge in SI/E within IS research. Addressing this gap, our research aims to organise the literature, identify trends and gaps and propose future research directions for SI/E within IS. Recognising SI/E as an umbrella concept, we employ ontological analysis, offering a comprehensive depiction of the domain's scope, boundaries, key constructs and relationships. We construct an ontology of SI/E within IS and employ it to compare literature from 20 established IS journals with a broader range of publications—from this analysis, we examine 4211 articles and code 897. This analysis unveils potential research avenues and highlights the distinctive focus of IS scholarship in SI/E compared with other fields. The ontology aids in conceptualising the research landscape and guiding future investigations in SI/E in IS.

Boundary Value Problems for Equation with the Cauchy–Riemann Operator Singular Along the Boundary of a Rectangular Domain

Boundary Value Problems for Equation with the Cauchy–Riemann Operator Singular Along the Boundary of a Rectangular Domain

Modelling of superposition in 2D linear acoustic wave problems using Fourier Neural Operator networks

A method of solving the 2D acoustic wave equation using Fourier Neural Operator (FNO) networks is presented. Various scenarios including wave superposition are considered, including the modelling of multiple simultaneous sound sources, reflections from domain boundaries and diffraction from randomly-positioned and sized rectangular objects. Training, testing and ground-truth data is produced using the acoustic Finite-Difference Time-Domain (FDTD) method. FNO is selected as the neural architecture as the network architecture requires relatively little memory compared to some other operator network designs. The number of training epochs and the size of training datasets were chosen to be small to test the convergence properties of FNO in challenging learning conditions. It is demonstrated that an FNO network predicts wave behaviour faster than equivalent FDTD simulations. The use cases of FNO networks, including data compression and auralisation are considered and compared to existing operator network designs.

Hidden domain boundary dynamics toward crystalline perfection

A central paradigm of nonequilibrium physics concerns the dynamics of heterogeneity and disorder, impacting processes ranging from the behavior of glasses to the emergent functionality of active matter. Understanding these complex mesoscopic systems requires probing the microscopic trajectories associated with irreversible processes, the role of fluctuations and entropy growth, and the timescales on which nonequilibrium responses are ultimately maintained. Approaches that illuminate these processes in model systems may enable a more general understanding of other heterogeneous nonequilibrium phenomena, and potentially define ultimate speed and energy cost limits for information processing technologies. Here, we apply ultrafast single-shot X-ray photon correlation spectroscopy to resolve the nonequilibrium, heterogeneous, and irreversible mesoscale dynamics during a light-induced phase transition in a (PbTiO3)16/(SrTiO3)16 superlattice. Such ferroelectric superlattice systems are a useful platform to study phase transitions and topological dynamics due to their high degree of tunability. This provides an approach for capturing the nucleation of the light-induced phase, the formation of transient mesoscale defects at the boundaries of the nuclei, and the eventual annihilation of these defects, even in systems with complex polarization topologies. We identify a nonequilibrium correlation response spanning >10 orders of magnitude in timescales, with multistep behavior similar to the plateaus observed in supercooled liquids and glasses. We further show how the observed time-dependent long-time correlations can be understood in terms of stochastic and non-Markovian dynamics of domain walls, encoded in waiting-time distributions with power-law tails. This work defines possibilities for probing the nonequilibrium and correlated dynamics of disordered and heterogeneous media.

Why does my medical AI look at pictures of birds? Exploring the efficacy of transfer learning across domain boundaries

Why does my medical AI look at pictures of birds? Exploring the efficacy of transfer learning across domain boundaries

Hybrid Finite-Difference Physics-Informed Neural Networks Partial Differential Equation Solver for Complex Geometries

The physics-informed neural network (PINN) is effective in solving the partial differential equation (PDE) by capturing the physics constraints as a part of the training loss function through the automatic differentiation (AD). This study proposes the hybrid finite difference with PINN (HFD-PINN) to fully use the domain knowledge. The main idea is to use the finite-difference method (FDM) locally instead of AD in the framework of PINN. We use AD at complex boundaries and FDM in other domains. To avoid the background mesh, we propose HFD-PINN-sdf, which uses the signed distance function (sdf) to avoid the difference scheme from crossing the domain boundary. In this paper, we demonstrate the performance and compare the results with different numbers of collocation points and architectures for the Poisson equation and Burgers equation. We also chose several different finite-difference schemes, including the compact finite-difference and Crank–Nicolson methods, to verify the robustness of HFD-PINN. We take the heat conduction problem and the heat transfer problem on the irregular domain as examples to demonstrate the efficacy. In summary, HFD-PINN is more instructive and efficient when solving PDEs in complex geometries.

Uncovering topologically associating domains from three-dimensional genome maps with TADGATE.

Topologically associating domains (TADs) are essential components of three-dimensional (3D) genome organization and significantly influence gene transcription regulation. However, accurately identifying TADs from sparse chromatin contact maps and exploring the structural and functional elements within TADs remain challenging. To this end, we develop TADGATE, a graph attention auto-encoder that can generate imputed maps from sparse Hi-C contact maps while adaptively preserving or enhancing the underlying topological structures, thereby facilitating TAD identification. TADGATE captures specific attention patterns with two types of units within TADs and demonstrates TAD organization relates to chromatin compartmentalization with diverse biological properties. We identify many structural and functional elements within TADs, with their abundance reflecting the overall properties of these domains. We applied TADGATE to sparse and noisy Hi-C contact maps from 21 human tissues or cell lines. That improved the clarity of TAD structures, allowing us to investigate conserved and cell-type-specific boundaries and uncover cell-type-specific transcriptional regulatory mechanisms associated with topological domains. We also demonstrated TADGATE's capability to fill in sparse single-cell Hi-C contact maps and identify TAD-like domains within them, revealing the specific domain boundaries with distinct heterogeneity and the shared backbone boundaries characterized by strong CTCF enrichment and high gene expression levels.

Tunable Quantum Confinement in Individual Nanoscale Quantum Dots via Interfacial Engineering.

Introducing quantum confinement has shown promise to enable control of charge carriers. Although recent advances make it possible to realize confinement from semiclassical regime to quantum regime, achieving control of electronic potentials in individual nanoscale quantum dots (QDs) has remained challenging. Here, we demonstrate the ability to tune quantum confined states in individual nanoscale graphene QDs, which are realized by inserting nanoscale monolayer WSe2 islands in graphene/WSe2 heterostructures via interfacial engineering. Our experiment indicates that scanning tunneling microscope (STM) tip pulses can trigger a local phase transition in the interfacial nanoscale WSe2 islands, which, in turn, enables us to tune discrete quantum states in individual graphene QDs. By using a STM tip, we can also generate one-dimensional (1D) position-tunable domain boundaries in the WSe2 islands. The 1D boundary introduces atomically wide electrostatic barriers that bifurcate quasibound states into two regions in the graphene QD, changing the QD from a relativistic artificial atom to a relativistic artificial molecule.

Molecular dynamics investigation of heteroepitaxial growth of quaternary AlInGaN on wurtzite-GaN surface along [0001] direction

We conducted molecular dynamics simulations of heteroepitaxial vapor deposition of the AlInGaN film on the polar [0001] GaN surface to investigate the influence of the substrate temperature and Al/In ratio on the epitaxial film. Time- and position-dependent boundary constraints were implemented to ensure appropriate growth conditions in the vapor phase region, the near-surface solid, and the bulklike solid region of the growing film. The simulation utilized an optimized Stillinger–Weber potential to describe the interactions among Al–In–Ga–N atoms. For the compositional study, the ratios of Al/In used are 1/9, 3/7, 1/1, 7/3, and 9/1. To investigate the temperature effect on the substrate, four different growth temperatures above half of the simulated melting temperature of the GaN substrate were employed. Following the growth of the AlInGaN film, surface roughness, domain structure, crystallinity, and dislocations were analyzed. Our findings indicate that surface roughness and crystallinity increase with higher Al/In ratios as well as elevated substrate temperatures. The domain size was also observed to increase with higher Al/In ratios and temperatures. At lower temperatures and low Al/In ratios, islands of different polytypes emerge with a high height-to-width ratio, resulting in a highly polytypic structure. The annealing process following growth significantly improves crystallinity and reduces surface roughness. From the dislocation study, it was observed that the maximum number of dislocation lines is of type 1/3[11¯00], which relieve the lattice mismatch strain along the x- and y-directions, and dislocations are minimized at 2500 K. The observed trends in the effects of temperature and the Al-to-In content ratio on dislocations, voids, surface roughness, and domain boundary structures closely resemble known experimental observations in AlInGaN/GaN.

In-line tempering eliminates the domain boundary in perovskite single crystals for high-energy resolution ionizing radiation detectors.

Metal halide perovskite single crystals (SCs) emerge as a promising candidate for ionizing radiation detection. The realization of top-performing radiation detectors typically relies on careful crystal selection from broad candidate groups, as residual strain remains unavoidable during the SC growth process, which often leads to the formation of ferroelastic domains with varied orientations. Here, we introduce an in-line tempering strategy to alleviate microstrain and homogenize the domain orientation across methylammonium lead iodide (MAPbI3) perovskite SCs. The progressive strain relief during the phase transition in situ, demonstrated by the removal of ferroelastic domain walls, substantially enhances the crystallinity and the optoelectronic properties of the MAPbI3 SCs. As a result, the gamma-ray energy spectrum detector leveraging these strain-relaxed SCs achieves an energy resolution of 7.2% at 59.5 keV for a 241Am gamma-ray source, and the 25-pixel device performs highly uniformly with concentrated current distribution, which paves the way for its implementation in high-resolution radiation spectroscopy.

Evolutionary-numerical algorithm for unsteady inverse geometric problems in double-connected domains

Numerical solution of the problem of reconstruction of the inner boundary of the double-connected domain from the given Cauchy data on the outer part of the domain, for the heat and wave equations is considered. The inverse problem is reformulated as a minimization of the nonlinear functional. A real-valued genetic algorithm is used for the minimization. A tness function of the individual is proposed, for the calculation of which it is necessary to solve the non-stationary Dirichlet problem. For this problem, rst a semi discretization by the time variable is performed using the Rothe's method, and then the method of fundamental solutions is applied to the obtained recurrent sequence of stationary inhomogeneous problems. The proposed approach is easy to extend to the case of higher dimensions, therefore two dimensional and three dimensional domains are considered. The algorithm is tested on several examples for both equations and the stability of the method is con rmed for the noised input data.