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The interaction of ultrahigh-performance concrete (UHPC) and normal-strength concrete (NSC) is one of the main issues for strengthening conventional concrete structures or other applications where NSC and UHPC are interrelated. UHPC stands out for its strength and durability, while NSC is significantly inexpensive and easier to work with. Efficiently designed structures can exploit the advantages of both mixtures. At the interface of these materials in newly designed structures, the formwork can be modified at the interface to give the concrete surface sufficient roughness and thus cohesion as required. This improves both the tensile and shear strength of the contact resulting in the enhanced capacity of the composite structure. In this study, a button foil was inserted into the formwork for the UHPC and then a part of NSC was made. The shear strength of the interface without any stress component in the transverse direction was measured on small-scale samples. It was to justify the possibility of the use of this interface in real constructions such as beams and columns. The main objective of further research is to design a composite beam using a UHPC shell as formwork for NSC and protrusions at the interface. It is expected that the U-shaped shell made of the UHPC could significantly contribute to the load-bearing capacity of the resulting composite NSC–UHPC structure and also to its enhanced durability. In addition, if the NSC is enclosed in a shell of UHPC, it can be made from various secondary materials, therefore it can decrease cement consumption by more than 50%.

The cell migration cycle, well-established in 2D, proceeds with forming new protrusive structures at the cell membrane and subsequent redistribution of contractile machinery. Three-dimensional (3D) environments are complex and composed of 1D fibers, and 1D fibers are shown to recapitulate essential features of 3D migration. However, the establishment of protrusive activity at the cell membrane and contractility in 1D fibrous environments remains partially understood. Here the role of membrane curvature regulator IRSp53 is examined as a coupler between actin filaments and plasma membrane during cell migration on single, suspended 1D fibers. IRSp53 depletion reduced cell-length spanning actin stress fibers that originate from the cell periphery, protrusive activity, and contractility, leading to uncoupling of the nucleus from cellular movements. A theoretical model capable of predicting the observed transition of IRSp53-depleted cells from rapid stick-slip migration to smooth and slower migration due to reduced actin polymerization at the cell edges is developed, which is verified by direct measurements of retrograde actin flow using speckle microscopy. Overall, it is found that IRSp53 mediates actin recruitment at the cellular tips leading to the establishment of cell-length spanning fibers, thus demonstrating a unique role of IRSp53 in controlling cell migration in 3D. This work was supported by grants from the JSPS (KAKENHI JP20H03252, JP20KK0341, and JP21H05047) and JST CREST (JPMJCR1863) to S.S, and JST CREST (JPMJCR1863) to Y.M.K. N.S.G. is the incumbent of the Lee and William Abramowitz Professorial Chair of Biophysics and acknowledges support by the Ben May Center for Theory and Computation and the Israel Science Foundation (Grant No. 207/22). This research was made possible in part by the historic generosity of the Harold Perlman Family. A.S.N. acknowledges partial funding support from National Science Foundation (NSF, Grant No. 1762468 and 2119949). A.S.N. and B.B. acknowledge the Institute of Critical Technologies and Science (ICTAS) and Macromolecules Innovative Institute (MII) at Virginia Tech for their support in conducting this study. Published version

Metastasis is the main cause of death in cancer patients but remains a poorly understood process. Small cell lung cancer (SCLC) is one of the most lethal and most metastatic cancer types. SCLC cells normally express neuroendocrine and neuronal gene programs but accumulating evidence indicates that these cancer cells become relatively more neuronal and less neuroendocrine as they gain the ability to metastasize. Here we show that mouse and human SCLC cells in culture and in vivo can grow cellular protrusions that resemble axons. The formation of these protrusions is controlled by multiple neuronal factors implicated in axonogenesis, axon guidance, and neuroblast migration. Disruption of these axon-like protrusions impairs cell migration in culture and inhibits metastatic ability in vivo. The co-option of developmental neuronal programs is a novel molecular and cellular mechanism that contributes to the high metastatic ability of SCLC.

Surface textures have been demonstrated to have a positive effect on the friction reduction. However, sharp edges of the normally textured patterns usually cause stress concentration and severe wear during sliding, especially for non-conformal contacting pairs. In this study, protrusion-type textures were fabricated at different area ratios on stainless steel discs and edge profiling was performed for the protrusions, and friction tests were conducted in water to investigate the tribological properties. The results show that the friction was reduced markedly by edge profiling due to the formation of wedge contact and improvement of lubricant supply to the contact interfaces under low load. Under high load, severe wear destroyed the wedge contact resulting in high friction as those of the normally textured pairs. High area ratio exhibited better friction reduction effect. The stress analysis via ANSYS indicated that much high stress concentrated at the edges of the protrusions and could be reduced significantly by edge profiling.

The design of compact heat exchangers and their mass flow distributors is still based on empirical approaches and both numerical analyses and experimentations are needed for designing the best geometries useful to reduce the mass flow rate non uniformities in parallel channels. As known, this is indeed a cause of reduction in both thermal and fluid-dynamic performances. In this paper a series of single-phase CFD simulations on water and water with air injection are carried out in order to estimate the capabilities of the solvers implemented in the OpenFOAM code to reproduce (in comparison with experimental data) such kind of configurations and phenomena. The effects of different turbulence models (both RANS and LES) implemented in OpenFOAM are investigated; additionally some general considerations on the differences and analogies among different Reynolds numbers flow and turbulence model effects applied to the present configuration are discussed. Finally, the capability of the code to reproduce the peculiar behaviour of a protrusions based experimental facility is investigated, with the aim of obtaining an acceptable simulation of the non-uniform mass flow distribution in each protrusion. The present paper is an extended version including the main conclusions and observations emerged in the 2nd AIGE-IIETA International Conference in Genoa.

Next-generation sequencing has been invaluable in the elucidation of the genetic etiology of many subtypes of intellectual disability in recent years. Here, using exome sequencing and whole-genome sequencing, we identified three de novo truncating mutations in WAS protein family member 1 (WASF1) in five unrelated individuals with moderate to profound intellectual disability with autistic features and seizures. WASF1, also known as WAVE1, is part of the WAVE complex and acts as a mediator between Rac-GTPase and actin to induce actin polymerization. The three mutations connected by Matchmaker Exchange were c.1516C>T (p.Arg506Ter), which occurs in three unrelated individuals, c.1558C>T (p.Gln520Ter), and c.1482delinsGCCAGG (p.Ile494MetfsTer23). All three variants are predicted to partially or fully disrupt the C-terminal actin-binding WCA domain. Functional studies using fibroblast cells from two affected individuals with the c.1516C>T mutation showed a truncated WASF1 and a defect in actin remodeling. This study provides evidence that de novo heterozygous mutations in WASF1 cause a rare form of intellectual disability. ispartof: AMERICAN JOURNAL OF HUMAN GENETICS vol:103 issue:1 pages:144-153 ispartof: location:United States status: published

The plasticity of the cytoskeleton architecture and membrane properties is important for the establishment of cell polarity, adhesion and migration. Here, we present a method which combines stimulated emission depletion (STED) super-resolution imaging and atomic force microscopy (AFM) to correlate cytoskeletal structural information with membrane physical properties in live astrocytes. Using STED compatible dyes for live cell imaging of the cytoskeleton, and simultaneously mapping the cell surface topology with AFM, we obtain unprecedented detail of highly organized networks of actin and microtubules in astrocytes. Combining mechanical data from AFM with optical imaging of actin and tubulin further reveals links between cytoskeleton organization and membrane properties. Using this methodology we illustrate that scratch-induced migration induces cytoskeleton remodeling. The latter is caused by a polarization of actin and microtubule elements within astroglial cell processes, which correlates strongly with changes in cell stiffness. The method opens new avenues for the dynamic probing of the membrane structural and functional plasticity of living brain cells. It is a powerful tool for providing new insights into mechanisms of cell structural remodeling during physiological or pathological processes, such as brain development or tumorigenesis.

Taking advantage of good hermeticity, tiny parasitic capacitance, batch mode fabrication, and compatibility with multiple bonding techniques, the glass-silicon composite substrate manufactured by the glass reflow process has great potential to achieve 3D wafer-level packaging for high performance. However, the difference in etching characteristics between silicon and glass inevitably leads to the formation of the undesired micro-protrusions near the silicon-glass interface when preparing a shallow cavity etched around a few microns in the composite substrate. The micro-protrusions have a comparable height with the depth of the cavity, which increases the risks of damages to sensitive structures and may even trigger electrical breakdown, resulting in thorough device failure. In this paper, we studied the characteristics of the chemical composition and etching mechanisms at the interface carefully and proposed the corresponding optimized solutions that utilized plasma accumulation at the interface to accelerate etching and bridge the gap in etching rates between different chemical compositions. Finally, a smooth transition of 131.1 nm was achieved at the interface, obtaining an ideal etching cavity surface and experimentally demonstrating the feasibility of our proposal. The micromachining solution is beneficial for improving the yield and structural design flexibility of higher performance micro-electromechanical systems (MEMS) devices.

Different protein kinase C (PKC) isoforms have distinct roles in regulating cell functions. The conventional (α, β, γ) and novel (δ, e, η, θ) classes are targets of phorbol ester tumor promoters, which are surrogates of endogenous second messenger, diacylglycerol. The promoter-stimulated disappearance of filopodia was investigated by use of blocking peptides (BPs) that inhibit PKC maturation and/or docking. Filopodia were partially rescued by a peptide representing PKC e hydrophobic sequence, but also by a myristoylated PKC α/β pseudosubstrate sequence, and an inhibitor of T-cell protein tyrosine phosphatase (TC-PTP). The ability to turn over filopodia was widely distributed among PKC isoforms. PKC α and η hydrophobic sequences enhanced filopodia in cells in the absence of tumor promoter treatment. With transcriptional knockdown of PKC α, the content of PKC e predominated over other isoforms. PKC e could decrease filopodia significantly in promoter-treated cells, and this was attributed to ruffling. The presence of PKC α counteracted the PKC e-mediated enhancement of ruffling. The results showed that there were two mechanisms of filopodia downregulation. One operated in the steady-state and relied on PKC α and η. The other was stimulated by tumor promoters and relied on PKC e. Cycles of protrusion and retraction are characteristic of filopodia and are essential for the cell to orient itself during chemotaxis and haptotaxis. By suppressing filopodia, PKC e can create a long-term 'memory' of an environmental signal that may act in nature as a mnemonic device to mark the direction of a repulsive signal. This article is protected by copyright. All rights reserved.

Global and local analysis of the heat transfer in turbulent vortical flows is studied using three-dimensional numerical simulations. Vorticity is generated by inclined vortex generators in a turbulent circular pipe flow with twelve different configurations that fall into three categories. In the first category are rows of trapezoidal vortex generators in different arrangements; in the second category the vortex generators are fixed at certain distance from the tube wall, and the third category has vortex generator rows between which a row of small protrusions are inserted on the tube wall. First, a global analysis of the thermal performance is performed for all these configurations, which are also compared with other heat exchangers from the literature. New correlations for the friction factor and Nusselt number are then obtained. Local analysis of the effect of the flow structure on the temperature distribution is carried out for the four configurations showing the best performances. The local analysis involves studying the streamwise vorticity flux to characterize the convective transport process, the turbulent kinetic energy characterizing the turbulent mixing, and finally the local Nusselt number. (C) 2012 Elsevier Ltd. All rights reserved.

This study illuminates the aspects of cell migration, which is central to many biological processes. To understand cell migration we examine the relationship between local cytoskeletal features and local morphology. We demonstrate this relationship on cells stained for Actin and Myosin We connect the actin/myosin co-localizated structural organization to movements such as membrane protrusions. Membrane protrusions are good indicators of cell migration. Cells can sense the mechanical stiffness or the chemical identity of the surfaces they attach to. We show that these surfaces impact cytoskeletal structure. We develop a classifier to correlate the contextual features extracted from actin/myosin co-localized structure to different cell surfaces. We also describe a new distance based metric to measure the strength of collocated multi-channel two dimensional data for user selected regions. We provide tools, implemented as plugins for the popular ImageJ toolkit, that are available for download by the general public. These tools allow biologists to specify and score regions of interest by drawing a polygon on their image with a point and click interface. Furthermore, we provide an algorithm that automatically identifies, annotates, and scores an interesting donut shaped region commonly occurring in vascular smooth muscle cells on extra cellular matrix such as dry collagen, wet collagen, fibronectin and monolayer collagen.

Several bacterial pathogens, includingListeria monocytogenes,Shigella flexneriandRickettsiaspp., have evolved mechanisms to actively spread within human tissues. Spreading is initiated by the pathogen-induced recruitment of host filamentous (F)-actin. F-actin forms a tail behind the microbe, propelling it through the cytoplasm. The motile pathogen then encounters the host plasma membrane, forming a bacterium-containing protrusion that is engulfed by an adjacent cell. Over the past two decades, much progress has been made in elucidating mechanisms of F-actin tail formation.ListeriaandShigellaproduce tails of branched actin filaments by subverting the host Arp2/3 complex. By contrast,Rickettsiaforms tails with linear actin filaments through a bacterial mimic of eukaryotic formins. Compared with F-actin tail formation, mechanisms controlling bacterial protrusions are less well understood. However, recent findings have highlighted the importance of pathogen manipulation of host cell–cell junctions in spread.Listeriaproduces a soluble protein that enhances bacterial protrusions by perturbing tight junctions.Shigellaprotrusions are engulfed through a clathrin-mediated pathway at ‘tricellular junctions’—specialized membrane regions at the intersection of three epithelial cells. This review summarizes key past findings in pathogen spread, and focuses on recent developments in actin-based motility and the formation and internalization of bacterial protrusions.

An important role of cell matrix adhesion receptors is to mediate transmembrane coupling between extracellular matrix attachment, actin reorganization, and cell spreading. Thrombospondin (TSP)-1 is a modulatory component of matrix expressed during development, immune response, or wound repair. Cell adhesion to TSP-1 involves formation of biochemically distinct matrix contacts based on stable fascin spikes. The cell surface adhesion receptors required have not been identified. We report here that antibody clustering of syndecan-1 proteoglycan specifically transduces organization of cortical actin and fascin bundles in several cell types. Transfection of COS-7 cells with syndecan-1 is sufficient to stimulate cell spreading, fascin spike assembly, and extensive protrusive lateral ruffling on TSP-1 or on syndecan-1 antibody. The underlying molecular mechanism depends on glycosaminoglycan (GAG) modification of the syndecan-1 core protein at residues S45 or S47 for cell membrane spreading and on the VC2 region of the cytoplasmic domain for spreading and fascin spike formation. Expression of the VC2 deletion mutant or GAG-negative syndecan-1 showed that syndecan-1 is necessary in spreading and fascin spike formation by C2C12 cells on TSP-1. These results establish a novel role for syndecan-1 protein in coupling a physiological matrix ligand to formation of a specific matrix contact structure.