Topological Separation Research Articles

Unwinding of a eukaryotic origin of replication visualized by cryo-EM

To prevent detrimental chromosome re-replication, DNA loading of a double hexamer of the minichromosome maintenance (MCM) replicative helicase is temporally separated from DNA unwinding. Upon S-phase transition in yeast, DNA unwinding is achieved in two steps: limited opening of the double helix and topological separation of the two DNA strands. First, Cdc45, GINS and Polε engage MCM to assemble a double CMGE with two partially separated hexamers that nucleate DNA melting. In the second step, triggered by Mcm10, two CMGEs separate completely, eject the lagging-strand template and cross paths. To understand Mcm10 during helicase activation, we used biochemical reconstitution with cryogenic electron microscopy. We found that Mcm10 splits the double CMGE by engaging the N-terminal homo-dimerization face of MCM. To eject the lagging strand, DNA unwinding is started from the N-terminal side of MCM while the hexamer channel becomes too narrow to harbor duplex DNA.

Topological valley mode separation of elastic waves and potential applications

Topological metamaterials in condensed matter systems have shown significant potential for information and energy applications due to their novel wave propagation behaviors. Recently, there has been an increasing focus on studying topological metamaterials in classical wave systems. Elastic waves, as full-vector classical waves, possess more intricate mechanical characteristics compared to sound waves and electromagnetic waves. This complexity not only offers diverse practical application possibilities but also presents notable research challenges in the field of topological metamaterials. In this study, our main objective is to achieve the ideal mode separation of elastic waves, specifically separated into the in-plane and out-of-plane components, and explore its potential applications. Firstly, we design phononic crystals with dual Dirac cones. Through geometric perturbation, we successfully separate the valley Hall phases of in-plane and out-of-plane modes. By superimposing different topological phases, we achieve three types of topological edge states: in-plane waves, out-of-plane waves, and hybrid waves. Combining these different topological edge states enables us to effectively separate the elastic waves into in-plane and out-of-plane components. Furthermore, we investigate the potential application of mode separation in energy harvesting. We achieve the energy localization of different wave modes based on the topological whispering-gallery mode. Additionally, by utilizing piezoelectric materials, we realize the subregional energy harvesting of in-plane and out-of-plane modes. The mechanical properties resulting from mode separation and topological whispering-gallery mode hold great potential for signal filtering and energy storage, thereby opening up new possibilities for controlling and utilizing elastic waves in various engineering scenarios.

First report on chemometrics-driven multilayered lead prioritization in addressing oxysterol-mediated overexpression of G protein-coupled receptor 183.

Contemporary research has convincingly demonstrated that upregulation of G protein-coupled receptor 183 (GPR183), orchestrated by its endogenous agonist, 7α,25-dihydroxyxcholesterol (7α,25-OHC), leads to the development of cancer, diabetes, multiple sclerosis, infectious, and inflammatory diseases. A recent study unveiled the cryo-EM structure of 7α,25-OHC bound GPR183 complex, presenting an untapped opportunity for computational exploration of potential GPR183 inhibitors, which served as our inspiration for the current work. A predictive and validated two-dimensional QSAR model using genetic algorithm (GA) and multiple linear regression (MLR) on experimental GPR183 inhibition data was developed. QSAR study highlighted that structural features like dissimilar electronegative atoms, quaternary carbon atoms, and CH2RX fragment (X: heteroatoms) influence positively, while the existence of oxygen atoms with a topological separation of 3, negatively affects GPR183 inhibitory activity. Post assessment of true external set prediction capability, the MLR model was deployed to screen 12,449 DrugBank compounds, followed by a screening pipeline involving molecular docking, druglikeness, ADMET, protein-ligand stability assessment using deep learning algorithm, molecular dynamics, and molecular mechanics. The current findings strongly evidenced DB05790 as a potential lead for prospective interference of oxysterol-mediated GPR183 overexpression, warranting further in vitro and in vivo validation.

Steric repulsion introduced by loop constraints modulates the microphase separation of chromatins.

Within the confines of a densely populated cell nucleus, chromatin undergoes intricate folding, forming loops, domains, and compartments under the governance of topological constraints and phase separation. This coordinated process inevitably introduces interference between different folding strategies. In this study, we model interphase chromatins as block copolymers with hetero-hierarchical loops within a confined system. Employing dissipative particle dynamics simulations and scaling analysis, we aim to explain how the structure and distribution of loop domains modulate the microphase separation of chromatins. Our results highlight the correlation between the microphase separation of the copolymer and the length, heterogeneity, and hierarchically nested levels of the loop domains. This correlation arises from steric repulsion intrinsic to loop domains. The steric repulsion induces variations in chain stiffness (including local orientation correlations and the persistence length), thereby influencing the degree of phase separation. Through simulations of block copolymers with distinct groups of hetero-hierarchical loop anchors, we successfully reproduce changes in phase separation across diverse cell lines, under fixed interaction parameters. These findings, in qualitative alignment with Hi-C data, suggest that the variations of loop constraints alone possess the capacity to regulate higher-order structures and the gene expressions of interphase chromatins.

Conceptual process design and process optimization of triple-column pressure-swing distillation for the separation of ternary mixtures embedding two azeotropes with different feed composition via thermodynamic insights and genetic algorithm

In this article, we take the tetrahydrofuran (THF)/ethanol (ETOH)/methanol (MeOH) as an example to investigate the process design of the triple-column pressure-swing distillation (TCPSD) for the separation of Serafimov’s class 2.0-2b mixtures with different feed composition. Two basic topology structures (TSI, TSII) and two separation sequences (SSI, SSII) are investigated, then, process optimization with total annual cost (TAC) as objective function is conducted via genetic algorithms. Heat integration (HI) is also applied to TCPSD. From a new perspective, the separation of THF/ETOH/MeOH can be regarded as the azeotropic distillation for THF/ETOH with MeOH as azeotropic agents based on thermodynamic features of Serafimov’s class 2.0-2b mixtures. The feasible topology structure and separation sequence of TCPSD for Serafimov’s class 2.0-2b mixtures depend on the feed composition and operating pressure. The feed composition is divided into three regions according to the concentration of methanol in azeotropic distillation column. The two critical points are azeotropic points at allowed minimum and maximum operating pressure. Especially, when feed composition is below azeotropic point at allowed minimum operating pressure, TSI is not feasible due to less MeOH as azeotropic agents. Furthermore, TCPSD combining pure azeotropic agents (ATPSD) can be developed based on this new insight. Then, two feed compositions are used to illustrate the detailed conceptual design of three topology structures as well as corresponding two separation sequences and their economic performance. The results show that when feed composition is 0.4ETOH/0.25THF/0.35MeOH, TSI and TSII are feasible, the best economical configurations without and with heat integration is TSII-SSII and TSII-SSII-HI. When feed composition is 0.4ETOH/0.4THF/0.2MeOH, TSII and ATPSD are feasible, the best economical configurations without and with heat integration is ATPSD-SSI and ATPSD-SSI-HI. Furthermore, ATPSD-SSI and ATPSD-SSI-HI have 18.28% and 19.38% TAC reduction than TSII-SSI and TSII-SSI-HI, respectively. In summary, feasible and the best economic topology structure and separation sequence of TCPSD for Serafimov’s class 2.0-2b mixtures depend on the feed composition and operating pressure. In addition, the proposed ATPSD shows good economic performance for Serafimov’s class 2.0-2b mixtures.

The permanently chaperone-active small heat shock protein Hsp17 from Caenorhabditis elegans exhibits topological separation of its N-terminal regions

Small Heat shock proteins (sHsps) are a family of molecular chaperones that bind nonnative proteins in an ATP-independent manner. Caenorhabditis elegans encodes 16 different sHsps, among them Hsp17, which is evolutionarily distinct from other sHsps in the nematode. The structure and mechanism of Hsp17 and how these may differ from other sHsps remain unclear. Here, we find that Hsp17 has a distinct expression pattern, structural organization, and chaperone function. Consistent with its presence under nonstress conditions, and in contrast to many other sHsps, we determined that Hsp17 is a mono-disperse, permanently active chaperone invitro, which interacts with hundreds of different C.elegans proteins under physiological conditions. Additionally, our cryo-EM structure of Hsp17 reveals that in the 24-mer complex, 12 N-terminal regions are involved in its chaperone function. These flexible regions are located on the outside of the spherical oligomer, whereas the other 12 N-terminal regions are engaged in stabilizing interactions in its interior. This allows the same region in Hsp17 to perform different functions depending on the topological context. Taken together, our results reveal structural and functional features that further define the structural basis of permanently active sHsps.

Topology and dimension synchronous optimization design of 5-DoF parallel robots for in-situ machining of large-scale steel components

Robotic machining has been successfully applied in thin-walled aluminum alloy components, but its ability to machine large steel components in-situ remains to be improved. To address this issue, a class of five-degree-of-freedom (5-DoF) parallel machining robots with high stiffness-mass ratio, easy installation, compact structure and reconfigurability is designed. To solve the problem of separation of topology and dimension designs, a topology and dimension synchronous optimization design method is proposed by parametric characterization and performance differential map of the robot. Three performance indices, namely, axial stiffness, feed stiffness, and mass are mainly considered. The influences of topology and layout on the performance are extensively investigated. We developed a full-size prototype according to the optimization results. Prototype data demonstrates that the 5-DoF parallel robot offers satisfactory static behavior, thereby fulfilling the essential requirements for the in-situ machining of large-scale steel components. Lastly, several in-situ machining robotic solutions are presented, thereby laying the foundation for other in-situ machining of large-scale steel components.

Projective Points Over Matrices and Their Separability Properties

In this article we consider topological quotients of real and complex matrices by various subgroups and their connections to spacetime structures. These spaces are naturally interpreted as projective points. In particular, we look at quotients of nonzero matrices M^*_2({mathbb {F}}) by GL_2({mathbb {F}}),SL_2({mathbb {F}}),O_2({mathbb {F}}), and SO_2({mathbb {F}}) and prove various results about their topological separability properties. We discuss the interesting result that, as the group we quotient by gets smaller, the separability properties of the quotient improve.

Functional stratification of cancer drugs through integrated network similarity

Drugs not only perturb their immediate protein targets but also modulate multiple signaling pathways. In this study, we explored networks modulated by several drugs across multiple cancer cell lines by integrating their targets with transcriptomic and phosphoproteomic data. As a result, we obtained 236 reconstructed networks covering five cell lines and 70 drugs. A rigorous topological and pathway analysis showed that chemically and functionally different drugs may modulate overlapping networks. Additionally, we revealed a set of tumor-specific hidden pathways with the help of drug network models that are not detectable from the initial data. The difference in the target selectivity of the drugs leads to disjoint networks despite sharing a similar mechanism of action, e.g., HDAC inhibitors. We also used the reconstructed network models to study potential drug combinations based on the topological separation and found literature evidence for a set of drug pairs. Overall, network-level exploration of drug-modulated pathways and their deep comparison may potentially help optimize treatment strategies and suggest new drug combinations.

Effects of Amplitude, Maximal Lyapunov Exponent, and Kaplan–Yorke Dimension of Dynamical Oscillators on Master Stability Function

Obtaining the master stability function is a well-known approach to study the synchronization in networks of chaotic oscillators. This method considers a normalized coupling parameter which allows for a separation of network topology and local dynamics of the nodes. The present study aims to understand how the dynamics of oscillators affect the master stability function. In order to examine the effect of various characteristics of oscillators, a flexible oscillator with adjustable amplitude, Lyapunov exponent, and Kaplan–Yorke dimension is used. Not surprisingly, it is demonstrated that the amplitude of the oscillations has no substantial effect on the master stability function, i.e. the coupling strength needed for the complete synchronization is not changed. However, the flexible oscillators with larger maximal Lyapunov exponent synchronize with larger coupling strength. Interestingly, it is shown that there is no linear connection between the Kaplan–Yorke dimension and coupling strength needed for complete synchronization.

Covering action on Conley index theory

AbstractIn this paper we apply Conley index theory in a covering space of an invariant set S, possibly not isolated, in order to describe the dynamics in S. More specifically, we consider the action of the covering translation group in order to define a topological separation of S which distinguishes the connections between the Morse sets within a Morse decomposition of S. The theory developed herein generalizes the classical connection matrix theory, since one obtains enriched information on the connection maps for non-isolated invariant sets, as well as for isolated invariant sets. Moreover, in the case of an infinite cyclic covering induced by a circle-valued Morse function, one proves that the Novikov differential of f is a particular case of the p-connection matrix defined herein.

Topological Sigma-Semiring Separation and Ordered Measures in Noetherian Hyperconvexes

The interplay between topological hyperconvex spaces and sigma-finite measures in such spaces gives rise to a set of analytical observations. This paper introduces the Noetherian class of k-finite k-hyperconvex topological subspaces (NHCs) admitting countable finite covers. A sigma-finite measure is constructed in a sigma-semiring in a NHC under a topological ordering of NHCs. The topological ordering relation maintains the irreflexive and anti-symmetric algebraic properties while retaining the homeomorphism of NHCs. The monotonic measure sequence in a NHC determines the convexity and compactness of topological subspaces. Interestingly, the topological ordering in NHCs in two isomorphic topological spaces induces the corresponding ordering of measures in sigma-semirings. Moreover, the uniform topological measure spaces of NHCs need not always preserve the pushforward measures, and a NHC semiring is functionally separable by a set of inner-measurable functions.

Research on Inverse Kinematics of Manipulator Based on Neural Network

The inverse kinematics solution of manipulator is an important part of robot dynamics, trajectory planning and trajectory tracking control. This paper presents an inverse kinematics solution method of manipulator in which the RBF network is used. This method overcomes many defects of traditional inverse kinematics solution methods, such as low precision and slow convergence speed, and provides a new solution for the inverse kinematics of manipulator. Experimental results show that the RBF network has compact topological structure, separation and learning of structural parameters, fast convergence speed and global approximation ability, which fundamentally solves the local optimization problem of BP network. The scheme designed in this paper is simple and practical, and the trained parallel neural network has fast convergence speed and high precision, which can meet the requirements of high-speed inverse kinematics in the real-time control of manipulator.

Ligand Bent-Angle Engineering for Tuning Topological Structures and Acetylene Purification Performances of Copper-Diisophthalate Frameworks.

To enrich structural chemistry and widen the application prospects of MOFs (metal-organic frameworks), the development of a synthetic strategy to realize structural and functional modulation is highly demanded. By implementation of the linker bent-angle engineering strategy, three banana-like diisophthalate linkers with distinct bent angles were designed and synthesized. The inclusion of the targeted linkers into MOFs through solvothermal assembly with CuCl2·2H2O under identical conditions yielded three crystalline solids featuring diversified topological structures as revealed by X-ray crystallographic studies. Furthermore, functional explorations indicated that they are promising solid adsorbents for acetylene (C2H2) purification application with structurally dependent separation potentials. The results reported in this study illustrated a rare example of modulating the topological structures and separation efficiencies of MOFs by engineering the ligand bent angles.

Skeletal-based microstructure representation and convolution reconstruction

This paper introduces the skeletal-based microstructure representation. The skeletal representation allows for compact storage while capturing the main characteristics of the microstructure; and the separation of geometry and topology. The skeletal representation consists of two elements: primitive-based skeleton, representing topology, and a kernel representing the shape of the primitives in the skeleton. We supplement the representation with three operations: skeletonization, primitive identification, and convolution of the skeleton with a kernel. To demonstrate the robustness of the representation, we perform a quantitative study to show the decrease in the number of parameters needed to represent the several types of microstructure with respect to the voxel-based representation. We report a low error of reconstruction of the proposed representation method.

Variable temperature asymmetric flow field-flow fractionation for the topology separation of poly(methyl methacrylate)

Size exclusion chromatography is the method of choice for the molar mass analysis of polymers, however, it is not selective towards polymer microstructure. Counterintuitively, asymmetric flow field-flow fractionation (AF4), a channel-based molar mass analysis technique, has been shown to be able to fractionate poly(methyl methacrylate (PMMA) according to tacticity. This was revealed by investigating the solution behaviour of syndiotactic- (s-PMMA), atactic- (a-PMMA) and isotactic (i-PMMA) poly(methyl methacrylate) of similar molecular masses in solvents with different thermodynamic properties. In addition to developing a selective fractionation method, the effects of solvent quality and channel temperature on the fractionation were investigated. It was concluded that the thermodynamic quality of the carrier liquid has a significant influence on the retention behaviour of polymers in AF4. It was shown that the separation of s-PMMA and i-PMMA can be improved by using a theta solvent (acetonitrile) as the carrier liquid instead of thermodynamically good solvents such as tetrahydrofuran and chloroform. In addition, it was found that by using a non-stereocomplexing solvent for PMMA, such as chloroform, blends of s-PMMA and i-PMMA can be separated. Lastly, it was established that the AF4 channel temperature has an influence on the retention behaviour of the PMMA samples. For THF as carrier liquid it was found that the maximum difference in retention between s-PMMA and i-PMMA can be achieved at a channel temperature of 35 °C. In the case of ACN being the carrier liquid, it was observed that the retention behaviour of i-PMMA was significantly more influenced by a change in temperature as compared to s-PMMA and a-PMMA.

Nuclear modification factors, directed and elliptic flow of electrons from open heavy flavor decays in Au+Au collisions from STAR

We present the analyses of single electrons from semileptonic bottom and charm hadron decays at mid-rapidity in sNN=200and54.4GeV Au+Au collisions (talk in Heavy-Flavor session III). The data at sNN=200GeV incorporate information from the Heavy Flavor Tracker which enables the topological separation of electrons originating from bottom and charm hadron decays. We report the first STAR measurements at sNN=200GeV of ν2 for bottom decay electrons as a function of pT and ν1 for charm decay electrons as a function of electron rapidity. Additionally, we present the improved measurements of heavy-flavor decay electron RAA and a new measurement of the ratio of RCP between bottom and charm decay electrons. Finally, we also report the measurement of non-photonic electron ν2 in sNN=54.4GeV data collected during the 2017 RHIC run.

ClusterM: a scalable algorithm for computational prediction of conserved protein complexes across multiple protein interaction networks

BackgroundThe current computational methods on identifying conserved protein complexes across multiple Protein-Protein Interaction (PPI) networks suffer from the lack of explicit modeling of the desired topological properties within conserved protein complexes as well as their scalability.ResultsTo overcome those issues, we propose a scalable algorithm—ClusterM—for identifying conserved protein complexes across multiple PPI networks through the integration of network topology and protein sequence similarity information. ClusterM overcomes the computational barrier that existed in previous methods, where the complexity escalates exponentially when handling an increasing number of PPI networks; and it is able to detect conserved protein complexes with both topological separability and cohesive protein sequence conservation. On two independent compendiums of PPI networks from Saccharomyces cerevisiae (Sce, yeast), Drosophila melanogaster (Dme, fruit fly), Caenorhabditis elegans (Cel, worm), and Homo sapiens (Hsa, human), we demonstrate that ClusterM outperforms other state-of-the-art algorithms by a significant margin and is able to identify de novo conserved protein complexes across four species that are missed by existing algorithms.ConclusionsClusterM can better capture the desired topological property of a typical conserved protein complex, which is densely connected within the complex while being well-separated from the rest of the networks. Furthermore, our experiments have shown that ClusterM is highly scalable and efficient when analyzing multiple PPI networks.

Robust Event-Triggered Dynamic Average Consensus Against Communication Link Failures With Application to Battery Control

Dynamic average consensus (DAC) has found applications in various systems. The existing event-triggered DAC algorithms have not well addressed the issue of key communication link failures that lead to the separation of the initial communication topology. This article presents a modified event-triggered DAC algorithm that is independent of its initial conditions. As a result, it is robust against key communication link failures. In this algorithm, each agent decides locally when to transmit signals to its neighbors. In this way, the communication burden among the neighboring agents is reduced. A numerical example is provided to illustrate the effectiveness of the proposed algorithm. Moreover, the proposed algorithm is applied to a state-of-charge balance control problem of batteries in energy systems, and both simulations and hardware-in-the-loop tests are provided to demonstrate the control performance.

Advective mass transport in two side-by-side liquid microspheres

Gaseous entrainment from a contaminated outer air stream into a pair of side-by-side homogeneous and heterogeneous micro-sized water drops is numerically examined for varied gap ratio (ratio of interfacial gap to radius), Reynolds number , Weber number , and liquid-phase Peclet number . For and , the separation–attachment induced momentum exchange and imposed non-uniform interfacial shear stress lead to breakup of the primary Hill’s vortex ring and create a significant secondary vortex ring in each drop, which together construct a dominant advective transport mechanism therein. Beneath a three-dimensional (3-D) topological separation line, the study identifies an active advective mass entrainment process that is led by the ‘inflow’ natured local dynamics of this primary–secondary vortex ring pair. Mechanistically, the secondary and primary vortex rings regulate species transfer into a drop by maintaining the spontaneous inflow-type counter-rotating motion along the 3-D separation line, whereby the is entrained; and near the attachment points/nodes, two vortices distinctly repulse entry by virtue of their ‘outflow’ natured local dynamics. The blockage effect and nozzle effect on flow approaching and passing the narrow neck that formed in the presence of a second drop lead to the asymmetric growth of both primary and secondary vortex rings via the locally weakened and enhanced near-interfacial air flow and imposed variable shear stress, which induce the occurrence of an asymmetric mass transfer phenomenon plus biased saturation. The , once entrained, rotates mostly along a spiral orbit of a primary vortex ring, owing to its higher strength. For increased , the transport process is reinforced following increased strength of the inflow paired secondary–primary vortex dynamics that enhanced the net entrainment rate and also advanced its transport to the vortex core via augmented convective flow plus radial diffusion. A narrow gap facilitated faster near-gap saturation, while the quantitative transport rate is decreased by virtue of the produced tapered primary–secondary vortex pairs, associated inner flow bifurcation, and changed topology of the separated wake, which appear similar to what develops for a larger single drop. The gap induced inner vortical structures are characterized by a weaker secondary vortex and a tapered primary vortex near the neck. For heterogeneous drop pairs, the influence of varying 3-D surface flow topology on the two interfaces and the impact of solid fraction ( , with being the radius of the solid core) on the created advective mechanism by the primary–secondary vortex ring pair and resultant transport are exclusively elucidated.