Transient Structures Research Articles

Dual-kernel driven convolutional sparse learning for bearing transient feature enhancement

The transient structure feature of bearing reflects the dynamic response of vibration, which is of vital importance for rotating machinery fault diagnosis. However, the measured signals are complicated and non-stationary, where the transient impacts are always submerged in heavy background noise. In this study, a novel dual-kernel driven convolutional sparse learning (DKCSL) is proposed to enhance the transient feature with the intrinsic structure mined. Considering the benefits of data-driven representation with time–frequency manifold (TFM) learning and model-driven representation with wavelet analysis, two time–frequency kernels with different principles are constructed for 2-dimensional convolutional sparse learning (CSL) in a fusion way of both data-driven and model-driven. From the perspective of image processing, the representation of desired transient structure features can be well sensed from time-frequency distribution (TFD) by those two dual-driven time–frequency kernels. In this manner, the desired defective intrinsic features can be mined, which is consistent with the physical dynamic response. In addition, image entropy is introduced to output the optimal TFM kernel and a series of inverse transform are applied to obtain the enhanced signal waveform. Simulated and experimental data are tested here to verify the creativity and effectiveness of the proposed DKCSL method, and a comparison with the traditional single TFM kernel-based sparse result and wavelet kernel-based sparse result are further provided, which deeply indicates the originality of our method that its potential in intrinsic structure feature extraction with dual-kernel sensing for bearing fault diagnosis.

Topology Optimization of Transient Thermo-elastic Structure Considering Regional Temperature Control

Topology Optimization of Transient Thermo-elastic Structure Considering Regional Temperature Control

Axisymmetric viscous overstability in fully self-gravitating systems. Conditions for the onset of overstable oscillations

ABSTRACT We examine the onset of viscous overstability in dense self-gravitating particle rings. This oscillatory instability offers a plausible explanation for the periodic radial density variations seen at several locations of Saturn’s B and inner-A ring. So far, the theoretical understanding of overstable ring systems relies mainly on analytical results based on approximate treatments of ring self-gravity which omit the emergence of self-gravity wakes (small-scale gravitational instabilities). Therefore, the interplay between the two mechanisms, self-gravity and overstability, is still not well understood. Here, we address numerically the factors that determine the onset of overstability in self-gravitating rings. We confirm that weak self-gravity promotes overstability whereas strong self-gravity, with prominent wake structure, weakens the overstable pattern. This strong gravity regime corresponds to optical depths beyond a threshold value. In systems where overstable oscillations and wakes co-exist, we detect a strong anticorrelation between the strength of wakes and overstable oscillations. It is this interaction that eventually leads to the suppression of overstability, with strong transient wake structure preventing the phase synchronization between density and velocity oscillations required to maintain a coherent overstable pattern. Finally, we derive a composite criterion for the onset of overstability valid even in the regime of strong gravity wakes, framed in terms of collective properties of the system: the central-plane filling factor and the ratio of gravitational and collisional viscosities. In the limit where gravity wakes are omitted, our new criterion agrees with that found by the kinetic theory analysis of linear stability.

Rab GTPases, tethers, and SNAREs work together to regulate Arabidopsis cell plate formation.

Cell plates are transient structures formed by the fusion of vesicles at the center of the dividing plane; furthermore, these are precursors to new cell walls and are essential for cytokinesis. Cell plate formation requires a highly coordinated process of cytoskeletal rearrangement, vesicle accumulation and fusion, and membrane maturation. Tethering factors have been shown to interact with the Ras superfamily of small GTP binding proteins (Rab GTPases) and soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs), which are essential for cell plate formation during cytokinesis and are fundamental for maintaining normal plant growth and development. In Arabidopsis thaliana, members of the Rab GTPases, tethers, and SNAREs are localized in cell plates, and mutations in the genes encoding these proteins result in typical cytokinesis-defective phenotypes, such as the formation of abnormal cell plates, multinucleated cells, and incomplete cell walls. This review highlights recent findings on vesicle trafficking during cell plate formation mediated by Rab GTPases, tethers, and SNAREs.

Precision Ephemerides for Gravitational-wave Searches – IV. Corrected and refined ephemeris for Scorpius X-1

ABSTRACTLow-mass X-ray binaries have long been theorized as potential sources of continuous gravitational-wave radiation, yet there is no observational evidence from recent LIGO/Virgo observing runs. Even for the theoretically ‘loudest’ source, Sco X-1, the upper limit on gravitational-wave strain has been pushed ever lower. Such searches require precise measurements of the source properties for sufficient sensitivity and computational feasibility. Collating over 20 yr of high-quality spectroscopic observations of the system, we present a precise and comprehensive ephemeris for Sco X-1 through radial velocity measurements, performing a full homogeneous re-analysis of all relevant data sets and correcting previous analyses. Our Bayesian approach accounts for observational systematics and maximizes not only precision, but also the fidelity of uncertainty estimates – crucial for informing principled continuous-wave searches. Our extensive data set and analysis also enables us to construct the highest signal-to-noise ratio, highest resolution phase-averaged spectrum of a low-mass X-ray binary to date. Doppler tomography reveals intriguing transient structures present in the accretion disc and flow driven by modulation of the accretion rate, necessitating further characterization of the system at high temporal and spectral resolution. Our ephemeris corrects and supersedes previous ephemerides, and provides a factor three reduction in the number of templates in the search space, facilitating precision searches for continuous gravitational-wave emission from Sco X-1 throughout the upcoming LIGO/Virgo/KAGRA O4 observing run and beyond.

Nanoscale infrared spectroscopy identifies structural evolution of Aβ 16-22 fibrils from parallel to antiparallel beta sheets.

Spontaneous aggregation of amyloid beta (Aβ) proteins into fibrillar plaque is a key pathological signature of Alzheimer's disease. Structure of Aβ fibrils have been studied in depth; however, the structure of early-stage aggregates, such as oligomers and protofibrils, is less known. This lack of knowledge stems in part from the limits of experimental approaches used to study amyloid structure. Due to lack of spatial resolution, it is not always possible to isolate specific early-stage aggregates and identify their structural features using conventional biophysical techniques. This is particularly relevant for transient intermediate species. As a result, the structural evolution of amyloid aggregates from its early oligomers to mature fibril is still not fully understood. Atomic Force Microscopy (AFM), coupled with Infrared (IR) spectroscopy enables morphological and spectral characterization of individual nanoscale aggregates, and is thus ideally suited for this challenge. Here we have applied AFM-IR nano-spectroscopy to investigate the aggregation of Aβ 16-22, which spans the amyloidogenic core of the Aβ peptide. We demonstrate that Aβ 16-22 involves a structural transition from oligomers with parallel beta sheets to antiparallel fibrils through disordered intermediate fibril structures. This is exactly opposite to the known aggregation mechanism of the full-length Aβ. Furthermore, the transient fibrillar structures also exhibit signatures of alpha helices. Our results indicate that observing fibrils does not necessarily imply structural order, and that fibrils can undergo spontaneous reorganization to form more stable secondary structures.

Protein folding pathway and intermediates on the dimensionality reduced landscape with UMAP and native contact likelihood.

To understand protein folding mechanisms from molecular dynamics (MD) simulations, it is important to explore not only folded/unfolded states but also representative intermediate structures on the conformational landscape. Generally, such a conformational landscape is obtained by linear dimensionality reduction methods, principal component analysis (PCA) or time-lagged independent component analysis (tICA), for instance. However, it is often difficult to apply these linear methods to large-scale, nonlinear conformational changes such as protein folding. Here, we propose a novel approach to construct the landscape using the uniform manifold approximation and projection (UMAP) method, which nonlinearly reduces the dimensionality without losing data-point proximity. In the approach, native contact likelihood, a measure for native contact formation, is used as feature variables rather than the conventional Cartesian coordinates or dihedral angles of protein structures. We tested the performance of UMAP for coarse-grained MD simulation trajectories of B1 domain in protein G and observed on-pathway transient structures and other metastable states on the UMAP conformational landscape. In contrast, these structures were not clearly distinguished on the dimensionality reduced landscape using PCA or tICA. This approach is also useful to obtain dynamical information through Markov State Modeling and would be applicable to large-scale conformational changes in many other biomacromolecules.

Phosphorylation-dependent regulation of the transcriptional activity of Arabidopsis SOG1.

Eukaryotic organisms rely on the evolutionary conserved DNA damage response (DDR) mechanism to maintain genome integrity. Despite sharing many DDR components, plants lack the key mammalian DDR regulator called tumour suppressor P53. They use the functionally equivalent but otherwise unrelated plant-specific transcription factor SUPPRESSOR OF GAMMA RESPONSE 1 (SOG1) instead. Outside the conserved folded DNA-binding NAC domain, SOG1 is disordered and carries a net negative charge in its C-terminal tail. Using a high-throughput screening method in yeast, we located three putative SOG1 transcription activation domains (TAD). Two out of three are located in a C-terminal region and both comply with the Acidic Exposure Model of TAD function. In addition, those TADs are flanked by phosphorylation sites whose phosphorylation state contribute to the TAD's activity. The TADs biophysical properties are being determined and linked to their putative role as protein-protein interaction interfaces. Special interest goes out to the potential formation of transient structures in the disordered SOG1 C-terminus and its functional implications.

The Role of Transient Intermediate Structures in the Unfolding of the Trp-Cage Fast-Folding Protein: Generating Ensembles from Time-Resolved X-ray Solution Scattering with Genetic Algorithms.

The Trp-cage miniprotein is one of the smallest systems to exhibit a stable secondary structure and fast-folding dynamics, serving as an apt model system to study transient intermediates with both experimental and computational analyses. Previous spectroscopic characterizations that have been done on Trp-cage have inferred a single stable intermediate on a pathway from folded to unfolded basins. We aim to bridge the understanding of Trp-cage structural folding dynamics on microsecond-time scales, by utilizing time-resolved X-ray solution scattering to probe the temperature-induced unfolding pathway. Our results indicate the formation of a conformationally extended intermediate on the time scale of 1 μs, which undergoes complete unfolding within 5 μs. We further investigated the atomistic structural details of the unfolding pathway using a genetic algorithm to generate ensemble model fits to the scattering profiles. This analysis paves the way for direct benchmarking of theoretical models of protein folding ensembles produced with molecular dynamics simulations.

Femtosecond-resolved imaging of a single-particle phase transition in energy-filtered ultrafast electron microscopy

Using an energy filter in transmission electron microscopy has enabled elemental mapping at the atomic scale and improved the precision of structural determination by gating inelastic and elastic imaging electrons, respectively. Here, we use an energy filter in ultrafast electron microscopy to enhance the temporal resolution toward the domain of atomic motion. Visualizing transient structures with femtosecond temporal precision was achieved by selecting imaging electrons in a narrow energy distribution from dense chirped photoelectron packets with broad longitudinal momentum distributions and thus typically exhibiting picosecond durations. In this study, the heterogeneous ultrafast phase transitions of vanadium dioxide (VO2) nanoparticles, a representative strongly correlated system, were filmed and attributed to the emergence of a transient, low-symmetry metallic phase caused by different local strains. Our approach enables electron microscopy to access the time scale of elementary nuclear motion to visualize the onset of the structural dynamics of matter at the nanoscale.

A replication fork determinant for the establishment of sister chromatid cohesion

Concomitant with DNA replication, the chromosomal cohesin complex establishes cohesion between newly replicated sister chromatids. Cohesion establishment requires acetylation of conserved cohesin lysine residues by Eco1 acetyltransferase. Here, we explore how cohesin acetylation is linked to DNA replication. Biochemical reconstitution of replication-coupled cohesin acetylation reveals that transient DNA structures, which form during DNA replication, control the acetylation reaction. As polymerases complete lagging strand replication, strand displacement synthesis produces DNA flaps that are trimmed to result in nicked double-stranded DNA. Both flaps and nicks stimulate cohesin acetylation, while subsequent nick ligation to complete Okazaki fragment maturation terminates the acetylation reaction. A flapped or nicked DNA substrate constitutes a transient molecular clue that directs cohesin acetylation to a window behind the replication fork, next to where cohesin likely entraps both sister chromatids. Our results provide an explanation for how DNA replication is linked to sister chromatid cohesion establishment.

FOXD1 is required for 3D patterning of the kidney interstitial matrix.

The interstitial extracellular matrix (ECM) is comprised of proteins and glycosaminoglycans and provides structural and biochemical information during development. Our previous work revealed the presence of transient ECM-based structures in the interstitial matrix of developing kidneys. Stromal cells are the main contributors to interstitial ECM synthesis, and the transcription factor Forkhead Box D1 (Foxd1) is critical for stromal cell function. To investigate the role of Foxd1 in interstitial ECM patterning, we combined 3D imaging and proteomics to explore how the matrix changes in the murine developing kidney when Foxd1 is knocked out. We found that COL26A1, FBN2, EMILIN1, and TNC, interstitial ECM proteins that are transiently upregulated during development, had a similar distribution perinatally but then diverged in patterning in the adult. Abnormally clustered cortical vertical fibers and fused glomeruli were observed when Foxd1 was knocked out. The changes in the interstitial ECM of Foxd1 knockout kidneys corresponded to disrupted Foxd1+ cell patterning but did not precede branching dysmorphogenesis. The transient ECM networks affected by Foxd1 knockout may provide support for later-stage nephrogenic structures.

The role of transient plasma photonic structures in plasma-based amplifiers

High power lasers have become useful scientific tools, but their large size is determined by their low damage-threshold optical media. A more robust and compact medium for amplifying and manipulating intense laser pulses is plasma. Here we demonstrate, experimentally and through simulations, that few-millijoule, ultra-short seed pulses interacting with 3.5-J counter-propagating pump pulses in plasma, stimulate back-scattering of nearly 100 mJ pump energy with high intrinsic efficiency, when detuned from Raman resonance. This is due to scattering off a plasma Bragg grating formed by ballistically evolving ions. Electrons are bunched by the ponderomotive force of the beat-wave, which produces space-charge fields that impart phase correlated momenta to ions. They inertially evolve into a volume Bragg grating that backscatters a segment of the pump pulse. This, ultra-compact, two-step, inertial bunching mechanism can be used to manipulate and compress intense laser pulses. We also observe stimulated Compton (kinetic) and Raman backscattering.

Dynamic mode decomposition and reconstruction of the transient propeller wake under a light loading condition

This research aims to extend our understanding of propeller wake dynamics under a light loading condition, thereby laying a foundation for design optimization and flow control of the propeller. Dynamic mode decomposition (DMD) and reconstruction are used to analyze the transient vortical wake structures obtained by large eddy simulation. The propeller wake includes stable tip and hub vortices without interacting evolution at the light loading condition, and elliptical instabilities are observed downstream of the tip vortices. DMD describes the most energetic modes and the corresponding dominant frequencies are the blade passing frequency and its multiples. The coherent structures identified via DMD are primarily associated with the ordered convection of the tip vortices and have little correlation with the hub vortices. Additionally, the propeller wake flow is reconstructed using the first four DMD modes, and the primary wake features are well restored with a maximum reconstructed error of 7.98%. This demonstrates that the flow-field reconstruction based on the DMD reduced-order model is promising for predicting the propeller wake and controlling the propeller operation.

Effect of laser energy on protein conformation and lipid structure in skin tissue

This study explored the collagen distribution behavior, protein and lipid structure and function changes in the three-layer microstructure of skin tissue in the process of skin welding under different laser linear energies by Raman spectroscopy. The collagen deposition is a reversible thermal damage caused by laser linear energy not more than 7 J/m. Linear energy of 10 J/m can effectively increase the functional expression of lipoprotein, tryptophan and ceramide in the dermis, and can control the vibration of peptide chain in the reversible range. Also, the functions of various typical amino acids in the cuticle and epidermis can be well expressed under the condition of 7 J/m linear energy, while the damage of polypeptide chains is serious when the energy exceeds 12 J/m. The thermal stability of lipid components was significantly higher than that of collagen. The Raman peak intensity of sample responses were similar under the linearar energy conditions of 10 J/m and 5 J/m. At the same laser power, the higher the laser scanning speed, the smaller the thermal damage and the similar lipid transient structure could be obtained.

Analysis of Integrin-Dependent Melanoblast Migration During Development.

The neural crest is a transient embryonic structure that gives rise to a number of important cell types and tissues, including most of the peripheral and enteric nervous systems, pigment-producing skin cells known as melanocytes, and many craniofacial structures. Melanoblasts, the precursors of melanocytes, are derived from the so-called trunk neural crest cells. These cells delaminate and migrate along a dorsolateral pathway to colonize their final destination in the skin, and consequently, defects in melanoblast migration result in pigmentation defects. Studying melanocyte migration is a topic of great interest due to the involvement of melanocytes in highly metastatic skin cancer. A role for integrin-mediated adhesion is well established in neural crest migration, and our recent work has provided direct evidence for a key role for integrin-based adhesion in melanocyte migration. Imaging of melanoblast migration in the context of intact skin has proven to be a particularly powerful tool to study integrin-based adhesion during melanoblast migration. Here, we describe the use of skin explants combined with genetically encoded markers for melanocytes and high-resolution live imaging as a powerful and informative approach to analyze melanoblast migration in an ex vivo context.

Rationally designed stapled peptides allosterically inhibit PTBP1-RNA-binding.

The diverse role of the splicing factor PTBP1 in human cells has been widely studied and was found to be a driver for several diseases. PTBP1 binds RNA through its RNA-recognition motifs which lack obvious pockets for inhibition. A unique transient helix has been described to be part of its first RNA-recognition motif and to be important for RNA binding. In this study, we further confirmed the role of this helix and envisioned its dynamic nature as a unique opportunity to develop stapled peptide inhibitors of PTBP1. The peptides were found to be able to inhibit RNA binding via fluorescence polarization assays and directly occupy the helix binding site as observed by protein crystallography. These cell-permeable inhibitors were validated in cellulo to alter the regulation of alternative splicing events regulated by PTBP1. Our study demonstrates transient secondary structures of a protein can be mimicked by stapled peptides to inhibit allosteric mechanisms.

Assessment of nonlinear-low Reynolds number/detached eddy simulation turbulence model for wake flow field simulation of a realistic automotive model

Since the results of wake flow simulation with commonly used turbulence models are unsatisfactory, by introducing a nonlinear Reynolds stress term and combining the DES (Detached Eddy Simulation) model, this paper further validates the nonlinear-LRN (Low Reynolds Number)/DES turbulence model which can predict the flow separation and the reattachment phenomenon more accurately. This model was verified by a wall-mounted hump flow case and was applied to the time-averaged and transient flow field structure analysis of a realistic automotive model with several widely used turbulence models. These simulation results were compared with experimental data, indicating that the nonlinear-LRN/DES model gives better agreement with the experiment and can predict the automobile wake flow structures and aerodynamic characteristics more accurately. Furthermore, the performance of the nonlinear-LRN/DES model in mesh with different refinements is compared, concluding that the new proposed model can obtain high accuracy in the coarse mesh.

From a one-mode to a multi-mode understanding of conical intersection mediated ultrafast organic photochemical reactions.

Over the last few decades, conical intersections (CoIns) have grown from theoretical curiosities into common mechanistic features of photochemical reactions, whose function is to funnel electronically excited molecules back to their ground state in regions where the potential energy surfaces (PESs) of two electronic states become degenerate. Analogous to transition states in thermal chemistry, CoIns appear as transient structures providing a kinetic bottleneck along a reaction coordinate. However, such a bottleneck is not associated with the probability of crossing an energy barrier but rather with an excited state decay probability along a full "line" of transient structures connected by non-reactive modes, the intersection space (IS). This article will review our understanding of the factors controlling CoIn mediated ultrafast photochemical reactions, taking a physical organic chemist approach by discussing a number of case studies for small organic molecules and photoactive proteins. Such discussion will be carried out by first introducing the "standard" one-mode model based on Landau-Zener (LZ) theory to describe a reactive excited state decay event intercepting, locally, a single CoIn along a single direction, and then by providing a modern perspective based on the effects of the phase matching of multiple modes on the same local event, thus redefining and expanding the description of the excited state reaction coordinate. The direct proportionality between the slope (or velocity) along one mode and decay probability at a single CoIn is a widely applied fundamental principle that follows from the LZ model, yet it fails to provide a complete understanding of photochemical reactions whose local reaction coordinate changes along the IS. We show that in these situations, in particular by focussing on rhodopsin double bond photoisomerization, it is mandatory to consider additional molecular modes and their phase relationship approaching the IS, hence providing a key mechanistic principle of ultrafast photochemistry based on the phase matching of those modes. We anticipate that this qualitative mechanistic principle should be considered in the rational design of any ultrafast excited state process, impacting various fields of research ranging from photobiology to light-driven molecular devices.

Developmental switch from morphological replication to compensatory growth for salamander lung regeneration.

Salamanders possess a pair of lungs for active air breathing, but the lung respiration is fully operational only during the late stage of development, particularly after metamorphosis. Larval salamanders mainly exchange air through the gills and skin, thus sparing the developing lungs. Salamanders can repair their lungs after injury, but a comparative analysis of regenerative responses between the lungs of young and adult animals is lacking. In this study, lung resections were performed in both larval and adult newts (Pleurodeles waltl). The cellular dynamics, tissue morphology and organ function during lung regeneration were examined and the Yap mutants were produced with CRISPR tools. We found that salamanderswitches the regenerative strategies from morphological replication through the blastema formation to compensatory growth via resident epithelial cells proliferation upon pulmonary resection injury as it transitions beyond metamorphosis. The larval animals achieve lung regeneration by forming a transient blastema-like structure and regrowing full-sized developing lungs, albeit unventilated. The adults repair injured lungs via massive proliferating epithelial cells and by expanding the existing alveolar epithelium without neo-alveolarization. Yap signalling promotes epithelial cell proliferation and prevents epithelial-to-mesenchymal transition to restore functional respiration. The salamanders have evolved distinct regenerative strategies for lung repair during different phases of life. Our results demonstrate a novel strategy for functional lung recovery by inducing epithelial cell proliferation to strengthen the remaining alveoli without rebuilding new alveoli.