Network Junctions Research Articles

Density of Physical Network Junctions in the Amorphous Phase of Polyethylene and Its Copolymers: The Effect of Crystallinity, Domain Sizes, and Molecular Weight

Density of Physical Network Junctions in the Amorphous Phase of Polyethylene and Its Copolymers: The Effect of Crystallinity, Domain Sizes, and Molecular Weight

CircRNAs as Epigenetic Regulators of Integrity in Blood-Brain Barrier Architecture: Mechanisms and Therapeutic Strategies in Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease leading to progressive demyelination and neuronal loss, with extensive neurological symptoms. As one of the most widespread neurodegenerative disorders, with an age onset of about 30 years, it turns out to be a socio-health and economic issue, thus necessitating therapeutic interventions currently unavailable. Loss of integrity in the blood-brain barrier (BBB) is one of the distinct MS hallmarks. Brain homeostasis is ensured by an endothelial cell-based monolayer at the interface between the central nervous system (CNS) and systemic bloodstream, acting as a selective barrier. MS results in enhanced barrier permeability, mainly due to the breakdown of tight (TJs) and adherens junctions (AJs) between endothelial cells. Specifically, proinflammatory mediator release causes failure in cytoplasmic exposure of junctions, resulting in compromised BBB integrity that enables blood cells to cross the barrier, establishing iron deposition and neuronal impairment. Cells with a compromised cytoskeletal protein network, fiber reorganization, and discontinuous junction structure can occur, resulting in BBB dysfunction. Recent investigations on spatial transcriptomics have proven circularRNAs (circRNAs) to be powerful multi-functional molecules able to epigenetically regulate transcription and structurally support proteins. In the present review, we provide an overview of the recent role ascribed to circRNAs in maintaining BBB integrity/permeability via cytoskeletal stability. Increased knowledge of the mechanisms responsible for impairment and circRNA's role in driving BBB damage and dysfunction might be helpful for the recognition of novel therapeutic targets to overcome BBB damage and unrestrained neurodegeneration.

Influence of swelling on the elasticity of polymer networks cross-linked in the melt state: Test of the localization model of rubber elasticity.

The elasticity of polymer networks, formed by cross-linking high molecular mass polymers in the melt state and then swollen by a solvent, involves contributions from both the presence of cross-link network junctions and the interchain interactions associated with the combined effect of excluded volume interactions and topological constraints that become modified when the network is swollen. We test the capacity of the previously developed localization model of rubber elasticity, a mean field "tube model," to describe changes in elasticity observed in classical experimental studies of the mechanical properties of this type of network. In order to obtain a satisfactory comparison to the experiments, it was found to be necessary to account for the independently observed tendency of the network junctions to become localized in the network with appreciable swelling, as well as the interchain interactions emphasized in previous discussions of the localization model.

Nested non-covalent interactions expand the functions of supramolecular polymer networks

Supramolecular polymer networks contain non-covalent cross-links that enable access to broadly tunable mechanical properties and stimuli-responsive behaviors; the incorporation of multiple unique non-covalent cross-links within such materials further expands their mechanical responses and functionality. To date, however, the design of such materials has been accomplished through discrete combinations of distinct interaction types in series, limiting materials design logic. Here we introduce the concept of leveraging “nested” supramolecular crosslinks, wherein two distinct types of non-covalent interactions exist in parallel, to control bulk material functions. To demonstrate this concept, we use polymer-linked Pd2L4 metal–organic cage (polyMOC) gels that form hollow metal–organic cage junctions through metal–ligand coordination and can exhibit well-defined host-guest binding within their cavity. In these “nested” supramolecular network junctions, the thermodynamics of host-guest interactions within the junctions affect the metal–ligand interactions that form those junctions, ultimately translating to substantial guest-dependent changes in bulk material properties that could not be achieved in traditional supramolecular networks with multiple interactions in series.

Boron Nitride/Carbon Fiber High-Oriented Thermal Conductivity Material with Leaves-Branches Structure.

In the realm of thermal interface materials (TIMs), high thermal conductivity and low density are key for effective thermal management and are particularly vital due to the growing compactness and lightweight nature of electronic devices. Efficient directional arrangement is a key control strategy to significantly improve thermal conductivity and comprehensive properties of thermal interface materials. In the present work, drawing inspiration from natural leaf and branch structures, a simple-to-implement approach for fabricating oriented thermal conductivity composites is introduced. Utilizing carbon fibers (CFs), known for their ultra-high thermal conductivity, as branches, this design ensures robust thermal conduction channels. Concurrently, boron nitride (BN) platelets, characterized by their substantial in-plane thermal conductivity, act as leaves. These components not only support the branches but also serve as junctions in the thermal conduction network. Remarkably, the composite achieves a thermal conductivity of 11.08 W/(m·K) with just an 11.1 wt% CF content and a 1.86 g/cm3 density. This study expands the methodologies for achieving highly oriented configurations of fibrous and flake materials, which provides a new design idea for preparing high-thermal conductivity and low-density thermal interface materials.

Discontinuous Surface Ruptures and Slip Distributions in the Epicentral Region of the 2021 Mw7.4 Maduo Earthquake, China

Discontinuous Surface Ruptures and Slip Distributions in the Epicentral Region of the 2021 Mw7.4 Maduo Earthquake, China

Fibrin-Based Hydrogels with Reactive Amphiphilic Copolymers for Mechanical Adjustments Allow for Capillary Formation in 2D and 3D Environments.

This study focuses on enhancing controllable fibrin-based hydrogels for tissue engineering, addressing existing weaknesses. By integrating a novel copolymer, we improved the foundation for cell-based angiogenesis with adaptable structural features. Tissue engineering often faces challenges like waste disposal and nutrient supply beyond the 200 µm diffusion limit. Angiogenesis breaks through this limitation, allowing the construction of larger constructs. Our innovative scaffold combination significantly boosts angiogenesis, resulting in longer branches and more capillary network junctions. The copolymer attached to fibrin fibers enables precise adjustment of hydrogel mechanical dynamic properties for specific applications. Our material proves effective for angiogenesis, even under suppression factors like suramin. In our study, we prepared fibrin-based hydrogels with and without the copolymer PVP12400-co-GMA10mol%. Using a co-culture system of human umbilical vein endothelial cells (HUVEC) and mesenchymal stem cells (MSC), we analyzed angiogenetic behavior on and within the modified hydrogels. Capillary-like structures were reproducibly formed on different surfaces, demonstrating the general feasibility of three-dimensional endothelial cell networks in fibrin-based hydrogels. This highlights the biomaterial's suitability for in vitro pre-vascularization of biohybrid implants.

Saturated Micellar Networks: Phase Separation and Nanoemulsification Capacity

Different oils can be homogeneously dispersed in the network junctions of the separated bicontinuous micellar phases. Upon dilution, these dispersions spontaneously form nanoemulsions. The possibility of a micellar sponge phase formation in the case of mixtures with three anionic and two zwitterionic surfactants in the presence of divalent and monovalent salts is studied. The best results are obtained using sodium lauryl ether sulfate with 1 ethylene oxide group (SLES-1EO) and both cocamidopropyl betaine (CAPB) or N,N-dimethyldodecylamine N-oxide (DDAO) in the presence of an appropriate small amount of MgCl2 and CaCl2. Bicontinuous micellar phases can be produced also in high-salinity NaCl solutions. The bulk properties of these phases are independent of the concentration of the initial solutions from which they are separated, and their Newtonian viscosities are in the range from 0.3 Pa·s to 0.8 Pa·s. Both 8 wt% CAPB- and DDAO-containing sponge phases engulf up to 10 wt% limonene and spontaneously form nanoemulsion upon dilution with droplet sizes of 110–120 nm. Vitamin E can be homogeneously dispersed only in CAPB-containing saturated micellar network, and upon dilution, these dispersions spontaneously form nanoemulsions with smaller droplet sizes of 66 nm for both 8 diastereomers and 2 diastereomers mixtures of vitamin E.

Branching of axial compression histories of solid cylinders undergoing thermo-chemo-mechanical changes

This work considers the uniaxial compressive creep of a solid elastomeric circular cylinder under a fixed dead load as it undergoes time dependent and temperature dependent changes in its macromolecular structure. The changes occur at temperatures exceeding 100 °C and consist of chemical scission of macromolecular network junctions and their re-crosslinking to form new networks in new reference configurations. The scission process causes softening due to modulus reduction and the re-crosslinking causes stiffening due to deformation of newly formed networks. A condition is developed for the time when the homogeneous uniaxial creep deformation history develops an non-homogenous barrel shaped branch. Branching times and the corresponding compression ratio are calculated from this condition using mechanical and chemical scission properties from the experimental literature.

Towards Topological Geospatial Conflation: An Optimized Node-Arc Conflation Model for Road Networks

Geospatial data conflation is the process of identifying and merging the corresponding features in two datasets that represent the same objects in reality. Conflation is needed in a wide range of geospatial analyses, yet it is a difficult task, often considered too unreliable and costly due to various discrepancies between GIS data sources. This study addresses the reliability issue of computerized conflation by developing stronger optimization-based conflation models for matching two network datasets with minimum discrepancy. Conventional models match roads on a feature-by-feature basis. By comparison, we propose a new node-arc conflation model that simultaneously matches road-center lines and junctions in a topologically consistent manner. Enforcing this topological consistency increases the reliability of conflation and reduces false matches. Similar to the well-known rubber-sheeting method, our model allows for the use of network junctions as “control” points for matching network edges. Unlike rubber sheeting, the new model is automatic and matches all junctions (and edges) in one pass. To the best of our knowledge, this is the first optimized conflation model that can match nodes and edges in one model. Computational experiments using six road networks in Santa Barbara, CA, showed that the new model is selective and reduces false matches more than existing optimized conflation models. On average, it achieves a precision of 94.7% with over 81% recall and achieves a 99.4% precision when enhanced with string distances.

SIRT4 is a regulator of human skeletal muscle fatty acid metabolism influencing inner and outer mitochondrial membrane-mediated fusion

ObjectiveThe mitochondrial phenotype, governed by the balance of fusion-fission, is a key determinant of energy metabolism. The inner and outer mitochondrial membrane (IMM) fusion proteins optic atrophy 1 (OPA1) and Mitofusin 1 and 2 (Mfn1/2) play an important role in this process. Recent evidence also shows that Sirtuin 4 (SIRT4), located within the mitochondria, is involved in the regulation of fatty acid oxidation. The purpose of this study was to determine if SIRT4 expression regulates inner and outer mitochondrial-mediated fusion and substrate utilization within differentiated human skeletal muscle cells (HSkMC). Material and methodsSIRT4 expression was knocked down using small interfering RNA (siRNA) transfection in differentiated HSkMC. Following knockdown, mitochondrial respiration was determined by high-resolution respirometry (HRR) using the Oroboros Oxygraph O2k. Live cell confocal microscopy, quantified using the Mitochondrial Network Analysis (MiNA) toolset, was used to examine mitochondrial morphological change. This was further examined through the measurement of key metabolic and mitochondrial morphological regulators (mRNA and protein) induced by knockdown. ResultsSIRT4 knockdown resulted in a significant decrease in LEAK respiration, potentially explained by a decrease in ANT1 protein expression. Knockdown further increased oxidative phosphorylation and protein expression of key regulators of fatty acid metabolism. Quantitative analysis of live confocal imaging of fluorescently labelled mitochondria following SIRT4 knockdown supported the role SIRT4 plays in the regulation of mitochondrial morphology, as emphasized by an increase in mitochondrial network branches and junctions. Measurement of key regulators of mitochondrial dynamics illustrated a significant increase in mitochondrial fusion proteins Mfn1, OPA1 respectively, indicative of an increase in mitochondrial size. ConclusionsThis study provides evidence of a direct relationship between the mitochondrial phenotype and substrate oxidation in HSkMC. We identify SIRT4 as a key protagonist of energy metabolism via its regulation of IMM and OMM fusion proteins, OPA1 and Mfn1. SIRT4 knockdown increases mitochondrial capacity to oxidize fatty acids, decreasing LEAK respiration and further increasing mitochondrial elongation via its regulation of mitochondrial fusion.

Lunapark deficiency leads to an autosomal recessive neurodevelopmental phenotype with a degenerative course, epilepsy and distinct brain anomalies.

LNPK encodes a conserved membrane protein that stabilizes the junctions of the tubular endoplasmic reticulum network playing crucial roles in diverse biological functions. Recently, homozygous variants in LNPK were shown to cause a neurodevelopmental disorder (OMIM#618090) in four patients displaying developmental delay, epilepsy and nonspecific brain malformations including corpus callosum hypoplasia and variable impairment of cerebellum. We sought to delineate the molecular and phenotypic spectrum of LNPK-related disorder. Exome or genome sequencing was carried out in 11 families. Thorough clinical and neuroradiological evaluation was performed for all the affected individuals, including review of previously reported patients. We identified 12 distinct homozygous loss-of-function variants in 16 individuals presenting with moderate to profound developmental delay, cognitive impairment, regression, refractory epilepsy and a recognizable neuroimaging pattern consisting of corpus callosum hypoplasia and signal alterations of the forceps minor ('ear-of-the-lynx' sign), variably associated with substantia nigra signal alterations, mild brain atrophy, short midbrain and cerebellar hypoplasia/atrophy. In summary, we define the core phenotype of LNPK-related disorder and expand the list of neurological disorders presenting with the 'ear-of-the-lynx' sign suggesting a possible common underlying mechanism related to endoplasmic reticulum-phagy dysfunction.

High Atlastin 2-2 (ATL2-2) Expression Associates with Worse Prognosis in Estrogen-Receptor-Positive Breast Cancer.

The disruption of endoplasmic reticulum (ER) homeostasis occurs in many human diseases. Atlastins (ATLs) maintain the branched network of the ER. The dysregulation of ATL2, located at ER network junctions, has been associated with cancer. ATL2 is necessary for lipid droplet formation in murine breast tissue. Thus, we analyzed whether ATL2 has a role in human breast cancer (BC) pathology. The expression of ATL2 variant ATL2-2 was analyzed in breast tumors from the BC cohorts of the TCGA, METABRIC, and two independent Icelandic cohorts, Cohort 1 and 2; its association with clinical, pathological, survival, and cellular pathways was explored. ATL2-2 mRNA and protein expression were higher in breast tumors than in normal tissue. ATL2-2 mRNA associated with tumor characteristics that indicate a worse prognosis. In METABRIC, high ATL2-2 mRNA levels were associated with shorter BC-specific survival (BCSS) in patients with estrogen-receptor-positive luminal breast tumors, which remained significant after correction for grade and tumor size (HR 1.334, CI 1.063-1.673). Tumors with high ATL2 mRNA showed an upregulation of hallmark pathways MYC targets v1, E2F targets, and G2M checkpoint genes. Taken together, the results suggest that high levels of ATL2-2 may support BC progression through key cancer driver pathways.

A hybrid-dG method for singularly perturbed convection-diffusion equations on pipe networks

We study the numerical approximation of singularly perturbed convection-diffusion problems on one-dimensional pipe networks. In the vanishing diffusion limit, the number and type of boundary conditions and coupling conditions at network junctions change, which gives rise to singular layers at the outflow boundaries of the pipes. A hybrid discontinuous Galerkin method is proposed, which provides a natural upwind mechanism for the convection-dominated case. Moreover, the method provides a viable approximation for the limiting pure transport problem. A detailed analysis of the singularities of the solution and the discretization error is presented, and an adaptive strategy is proposed, leading to order optimal error estimates that hold uniformly in the singular perturbation limit. The theoretical results are confirmed by numerical tests.

Mechanisms of Salt Overspill at Estuarine Network Junctions Explained With an Idealized Model

AbstractSalt overspill, defined as the net salt transport from a channel of an estuarine network through a junction to another channel, can be a major contributor to salt intrusion. Here, an idealized subtidal model is constructed of a network consisting of one river channel and two sea channels, and used to investigate the sensitivity of overspill to different values of river discharge, tidal current, width, and depth of the channels. Two prototype systems are considered: the North and South Passage of the Yangtze Estuary and the Modaomen and Hongwan Channel of the Pearl River Estuary. Model results indicate that in both systems, increasing river discharge decreases the amount of salt overspill, except in the regime of weak river discharge in the Yangtze Estuary. Increasing the strength of the tidal current increases the overspill in the Yangtze Estuary, but it decreases the overspill in the Modaomen Estuary. Analysis of the model results shows that salt overspill is linearly related to the salinity difference at the upstream boundary of the two seaward channels, when they are considered as single channel estuaries. This salinity difference occurs because conditions in the channels are not identical, which results in different net water transports (causing export of salt), exchange flows, and horizontal diffusion (causing import of salt). An analytical expression is derived, which explains the dependency of salt overspill to the factors mentioned above.

FUS-ALS hiPSC-derived astrocytes impair human motor units through both gain-of-toxicity and loss-of-support mechanisms

BackgroundAstrocytes play a crucial, yet not fully elucidated role in the selective motor neuron pathology in amyotrophic lateral sclerosis (ALS). Among other responsibilities, astrocytes provide important neuronal homeostatic support, however this function is highly compromised in ALS. The establishment of fully human coculture systems can be used to further study the underlying mechanisms of the dysfunctional intercellular interplay, and has the potential to provide a platform for revealing novel therapeutic entry points.MethodsIn this study, we characterised human induced pluripotent stem cell (hiPSC)-derived astrocytes from FUS-ALS patients, and incorporated these cells into a human motor unit microfluidics model to investigate the astrocytic effect on hiPSC-derived motor neuron network and functional neuromuscular junctions (NMJs) using immunocytochemistry and live-cell recordings. FUS-ALS cocultures were systematically compared to their CRISPR-Cas9 gene-edited isogenic control systems.ResultsWe observed a dysregulation of astrocyte homeostasis, which resulted in a FUS-ALS-mediated increase in reactivity and secretion of inflammatory cytokines. Upon coculture with motor neurons and myotubes, we detected a cytotoxic effect on motor neuron-neurite outgrowth, NMJ formation and functionality, which was improved or fully rescued by isogenic control astrocytes. We demonstrate that ALS astrocytes have both a gain-of-toxicity and loss-of-support function involving the WNT/β-catenin pathway, ultimately contributing to the disruption of motor neuron homeostasis, intercellular networks and NMJs.ConclusionsOur findings shine light on a complex, yet highly important role of astrocytes in ALS, and provides further insight in to their pathological mechanisms.Graphical

Investigation of Optimum Sustainable Designs for Water Distribution Systems from Multiple Economic, Operational, and Health Perspectives

Optimizing the design of water distribution systems often faces difficulties due to continuous variations in water demands, pressure requirements, and disinfectant concentrations. The complexity of this optimization even increases when trying to optimize both the hydraulic and the water quality design models. Most of the previous works in the literature did not investigate the linkage between both models, either by combining them into one general model or by selecting any representative solution to proceed from one model to another. This work introduces an integrated two-step framework to optimize both designs while investigating the reasonable network configuration selection from the hydraulic design view before proceeding to the water quality design. The framework is mainly based on a modified version of the multi-objective particle swarm optimization algorithm. The algorithm’s first step is optimizing the hydraulic design of the network by minimizing the system’s capital cost while maximizing the system’s reliability. The second step targets optimizing the water quality design by minimizing both the total consumed chlorine mass and the accumulated differences between actual and maximum chlorine concentrations for all the network junctions. The framework is applied to Safi Network in Yemen. Three scenarios of the water quality design are proposed based on the selected decision variables. The results show a superior performance of the first scenario, based on optimized 24-h multipliers of a chlorine pattern for a flow-paced booster station, compared to the other scenarios in terms of the diversity of final solutions.

Effects of solvent conditions on the self-assembly of heterotrimeric collagen-like peptide (CLP) triple helices: a coarse-grained simulation study.

We perform coarse-grained (CG) molecular dynamics (MD) simulations to investigate the self-assembly of collagen-like peptide (CLP) triple helices into fibrillar structures and percolated networks as a function of solvent quality. The focus of this study is on CLP triple helices whose strands are different lengths (i.e., heterotrimers), leading to dangling 'sticky ends'. These 'sticky ends' are segments of the CLP strands that have unbonded hydrogen-bonding donor/acceptor sites that drive heterotrimeric CLP triple helices to physically associate with one another, leading to assembly into higher-order structures. We use a validated CG model for CLP in implicit solvent and capture varying solvent quality through changing strength of attraction between CG beads representing the amino acids in the CLP strands. Our CG MD simulations show that, at lower CLP concentrations, CLP heterotrimers assemble into fibrils and, at higher CLP concentrations, into percolated networks. At higher concentrations, decreasing solvent quality causes (i) the formation of heterogeneous network structures with a lower degree of branching at network junctions and (ii) increases in the diameter of network strands and pore sizes. We also observe a nonmonotonic effect of solvent quality on distances between network junctions due to the balance between heterotrimer end-end associations driven by hydrogen bonding and side-side associations driven by worsening solvent quality. Below the percolation threshold, we observe that decreasing solvent quality leads to the formation of fibrils composed of multiple aligned CLP triple helices, while the number of 'sticky ends' governs the spatial extent (radius of gyration) of the assembled fibrils.

Solute diffusion and partitioning in multi-arm poly(ethylene glycol) hydrogels.

Controlling solute transport in hydrogels is critical for numerous chemical separation applications, tissue engineering, and drug delivery systems. In previous review work, we have pointed out that proposed theoretical models and associated experiments tend to oversimplify the influence of the hydrogel structure on solute transport by addressing only the effects of the polymer volume fraction and mesh size of the networks on solute transport. Here, we reexamine these models by experimenting with a library of multi-arm poly(ethylene glycol) (PEG) hydrogels with simultaneous variations in four independent structural parameters. Standardized, high-throughput fluorescence recovery after photobleaching (FRAP) experiments in hydrogels characterize size-dependent solute diffusion and partitioning in each hydrogel formulation. Solute diffusivity dependence on junction functionality shows an influence from network geometry that is not addressed by mesh size-based models, experimentally validating the use of the geometry-responsive mesh radius in solute diffusivity modeling. Furthermore, the Richbourg-Peppas swollen polymer network (SPN) model accurately predicts how three of the four structural parameters affect solute diffusivity in hydrogels. Comparison with the large pore effective medium (LPEM) model showed that the SPN model better predicts solute size and hydrogel structure effects on diffusivity. This study provides a framework for investigating solute transport in hydrogels that will continue to improve hydrogel design for tissue engineering and drug delivery.

Traffic safety analysis for different road junctions in the Latvian national road network in the period from 2017-2019

Traffic organization must be safe, but according to traffic accident data, the highest number is at intersections. Different intersections are evaluated based on various criteria - road throughput, conflict points, number and severity of road traffic accidents. There are many different types of intersections in the road network, each of them is suitable for certain road parameters in the road network. In the main road network of the State of Latvia for the period 2017-2019, data was collected and places where road traffic accidents often occur were evaluated. Where one of the most important tasks was to find a rational way to improve safety without losing the importance of the road. The aim of this work is to analyze the impact of different intersections on the road network, as well as to provide recommendations for a safe consistent road network based on actual data.