Homogeneous Aggregates Research Articles

Heterogeneous Cadherin Expression and Multicellular Aggregate Dynamics in Ovarian Cancer Dissemination

Epithelial ovarian carcinoma spreads via shedding of cells and multicellular aggregates (MCAs) from the primary tumor into peritoneal cavity, with subsequent intraperitoneal tumor cell:mesothelial cell adhesion as a key early event in metastatic seeding. Evaluation of human tumor extracts and tissues confirms that well-differentiated ovarian tumors express abundant E-cadherin (Ecad), whereas advanced lesions exhibit upregulated N-cadherin (Ncad). Two expression patterns are observed: “mixed cadherin,” in which distinct cells within the same tumor express either E- or Ncad, and “hybrid cadherin,” wherein single tumor cell(s) simultaneously expresses both cadherins. We demonstrate striking cadherin-dependent differences in cell-cell interactions, MCA formation, and aggregate ultrastructure. Mesenchymal-type Ncad+ cells formed stable, highly cohesive solid spheroids, whereas Ecad+ epithelial-type cells generated loosely adhesive cell clusters covered by uniform microvilli. Generation of “mixed cadherin” MCAs using fluorescently tagged cell populations revealed preferential sorting into cadherin-dependent clusters, whereas mixing of cell lines with common cadherin profiles generated homogeneous aggregates. Recapitulation of the “hybrid cadherin” Ecad+/Ncad+ phenotype, via insertion of the CDH2 gene into Ecad+ cells, resulted in the ability to form heterogeneous clusters with Ncad+ cells, significantly enhanced adhesion to organotypic mesomimetic cultures and peritoneal explants, and increased both migration and matrix invasion. Alternatively, insertion of CDH1 gene into Ncad+ cells greatly reduced cell-to-collagen, cell-to-mesothelium, and cell-to-peritoneum adhesion. Acquisition of the hybrid cadherin phenotype resulted in altered MCA surface morphology with increased surface projections and increased cell proliferation. Overall, these findings support the hypothesis that MCA cadherin composition impacts intraperitoneal cell and MCA dynamics and thereby affects ultimate metastatic success.

Modeling Concrete Material Structure: A Two-Phase Meso Finite Element Model

Concrete is a compound material where aggregates are randomly placed within the cement paste. To describe the behavior of concrete structures at the ultimate, it is necessary to use nonlinear finite element models, which for shear and torsion problems do not always give satisfactory results. The current study aims at improving the modeling of concrete at the meso-level, which eventually can result in an improved assessment of existing structures. Concrete as a heterogeneous material is modeled consisting of hydrated cement paste and aggregates. The stress–strain curves of the hydrated cement paste and aggregates are described with results from the literature. A three-dimensional (3D) finite element model was developed to determine the influence of individual phases on the inelastic stress–strain distribution of concrete structures. A random distribution and morphology of the cement and aggregate fractions are achieved by using DREAM.3D. Two affordable computational dual-phase representative volume elements (RVEs) are imported to ABAQUS to be studied in compression and tension. The virtual specimens (concrete mesh) subjected to continuous monotonic strain loading conditions were constrained with 3D boundary conditions. Results demonstrate differences in stress–strain mechanical behavior in both compression and tension test simulations. A strong dependency of flow stress and plastic strain on phase type, aggregate (andesite) size, shape and distribution upon the composite local response are clearly observed. It is noted that the resistance to flow is higher in concrete meshes composed of finer and homogeneous aggregate particles because the Misses stresses and effective plastic strains are better distributed. This study shows that at the meso-level, concrete can be modeled consisting of aggregates and hydrated cement paste.

MESO-SCALE PARTICLE MODELING OF ALKALI-SILICA REACTION AND MECHANICAL PROPERTIES OF CONCRETE

A three-phase meso-scale model of concrete which consists of aggregate, mortar, and interface between aggregate and mortar is established by pre-processing approach and the particle flow code (PFC2D). A homogeneous aggregate expansion procedure is proposed to simulate alkali-aggregate reaction, and splitting tensile test is conducted to explore the mechanical properties of concrete subjected to the alkali-aggregate reaction. The numerical simulation shows that this model can effectively predict the expansion trend of concrete alkali aggregate reaction expansion; the splitting tensile strength of concrete subjected to the alkali-aggregate reaction fell sharply.

Low-energy structures of clusters modeled with competing repulsive and either long- or moderate short-range attractive interactions

We have employed an evolutionary algorithm (EA) to study the low-energy landscape of clusters modeled with a potential which is composed by an attractive Morse function and a repulsive Yukawa component. Since the range of the Morse potential is controlled by a single parameter (ρ), this has been varied between 3 and 14 to study its influence on the lowest-energy structure. The present results show that shorter-ranged attractive potentials tend to magnify the effect of the repulsive Yukawa function on the global minimum structure. Due to the higher energy-barriers, the short-range attractive interactions produce low-energy dissociated structures at smaller cluster sizes than long-range potentials. As a consequence of this, global minimum structures of clusters involving short-range attractive potentials tend to be elongated in order to reduce the number of second nearest-neighbor particles that usually correspond to a very repulsive contribution for the interaction energy. In addition, Bernal spirals and beaded-necklace motifs are often observed for potentials with a short-range attractive component, while long-ranged interactions can hardly support such structures. We have also searched for the global minima of the N=13 binary clusters formed by various combinations of the ρ-parameter in the Morse potential. Most of such binary clusters are unstable in relation to the corresponding N=13 homogeneous aggregates, and the structure tend to assume the usual icosahedral shape (especially for the cases involving the longer-range potentials) with particles associated to lower ρ-values preferentially located on the surface.

The role of surface charge in the desolvation process of gelatin: implications in nanoparticle synthesis and modulation of drug release.

The process of moving hydrophobic amino acids into the core of a protein by desolvation is important in protein folding. However, a rapid and forced desolvation can lead to precipitation of proteins. Desolvation of proteins under controlled conditions generates nanoparticles – homogeneous aggregates with a narrow size distribution. The protein nanoparticles, under physiological conditions, undergo surface erosion due to the action of proteases, releasing the entrapped drug/gene. The packing density of protein nanoparticles significantly influences the release kinetics. We have investigated the desolvation process of gelatin, exploring the role of pH and desolvating agent in nanoparticle synthesis. Our results show that the desolvation process, initiated by the addition of acetone, follows distinct pathways for gelatin incubated at different pH values and results in the generation of nanoparticles with varying matrix densities. The nanoparticles synthesized with varying matrix densities show variations in drug loading and protease-dependent extra- and intracellular drug release. These results will be useful in fine-tuning the synthesis of nanoparticles with desirable drug release profiles.

New U-Pb age constraints for the timing of gold mineralization at the Pampalo gold deposit, Archaean Hattu schist belt, eastern Finland, obtained from hydrothermally altered and recrystallised zircon

In this paper we present new U-Pb data on zircon and titanite from the host rocks of the Pampalo gold deposit located within the Neoarchaean Hattu schist belt in eastern Finland. We also present new U-Pb data on nearby plutonic rocks. Plagioclase porphyries at the mine site demonstrate inheritance from 2.82–2.83Ga sources while a suggestive intrusive age is at c. 2.76Ga. Zircon grains extracted from the altered felsic units hosting the gold ore show complex alteration and recrystallisation textures and demonstrate Zr mobility. This mobility is most probably related to the alteration event although direct link to gold mineralization remains to be shown. The preserved or recrystallized parts of the altered zircon grains, texturally homogeneous grain aggregates and some overgrowths yield heterogeneous ages which cluster between ca. 2.73 and 2.70Ga, with a mean age of 2.71Ga. This age is considered to place a new constraint on the timing of mobility of Au at the Pampalo. This event postdates the known crustal formation event at 2.76–2.73Ga in the area as recorded by the adjacent plutonic rocks and volcanoclastic rocks within the Hattu schist belt. The Naarva tourmaline granite, 10kmNW of Pampalo, is 2.69Ga and is thus temporally associated with known regional crustal anatexis and metamorphism in the Archaean of eastern Finland. Whether this crustal reworking event played a role in the genesis of the gold in eastern Finland needs to be further studied.

Synergistic Effects in Thermoplastic Polyurethanes Incorporating Hybrid Carbon Nanofillers

Abstract In this study thermoplastic polyurethane (TPUs) nanocomposites incorporating carbon nanotubes (CNTs) and graphene nanoplatelets (GNPs) were prepared via melt blending and compression molding and CNT dispersion was optimized by using non-covalent surface modification (surfactant). Filler dispersion was further improved by combining two fillers with different geometric shape and aspect ratio in hybrid filler nanocomposites. Synergistic effects were observed in the TPU-GNP-CNT hybrid composites, especially when combining GNP and CNT at a ratio of 6 : 4, showing higher tensile modulus and strength with respect to the systems incorporating individual CNTs and GNPs at the same overall filler concentration. This improvement was attributed to the interaction between CNTs and GNPs limiting GNP aggregation and bridging adjacent graphene platelets thus forming a more efficient network. Hybrid systems also exhibited improved creep resistance and recovery ability. Morphological analysis carried out by scanning electron microscopy (SEM) indicated that the hybrid nanocomposite presented slightly smaller and more homogeneous filler aggregates. The well-dispersed nanofillers also favored higher phase separation in TPU, as indicated by atomic force microscopy (AFM), resulting in a better microstructure able to enhance the load transfer and maximize the mechanical and viscoelastic properties.

Biologically inspired trajectory generation for swarming UAVs using topological distances

This paper presents a trajectory generation logic for a swarm of unmanned aerial vehicles which uses topological distances instead of metric values. Biologically inspired, this method evades exploiting distance measurements in the absence of such capabilities, as it happens in swarming birds. This newly developed trajectory generation logic provides a stable swarming logic which resembles a large aggregation of birds. The hypothesis of this work is that without depth perception, swarming birds rely primarily on their perception of other birds to estimate proximity and adjust repulsive and attractive forces in real-time. From previous biological behavior studies, it is known that a homogeneous and orderly aggregation is exhibited by swarming birds locating themselves side by side rather than in front or behind each other. This behavior, which is based on the relative spatial proximity perception to their nearest neighbors in the flock, allows birds to converge into a highly cohesive and coordinated formation without explicit control of inter-agent distances. Inspired by this biological pattern, a trajectory generation logic is designed and tested in controlling a multi-agent unmanned aerial systems without the use of inter-distances. A six degrees of freedom nonlinear dynamic model for an unmanned aircraft is used for simulation purposes. Each vehicle is provided with a decentralized agent-based robust nonlinear model predictive controller and a set of nonlinear guidance laws for trajectory tracking. The formulation of the proposed trajectory generation, as well as the selected aircraft control, constitute a truly decentralized technique, that allows for an unlimited number of agents within the swarm, as no centralized computations are made.

Determination of critical nucleation number for a single nucleation amyloid-β aggregation model

Aggregates of amyloid-β (Aβ) peptide are known to be the key pathological agents in Alzheimer disease (AD). Aβ aggregates to form large, insoluble fibrils that deposit as senile plaques in AD brains. The process of aggregation is nucleation–dependent in which the formation of a nucleus is the rate–limiting step, and controls the physiochemical fate of the aggregates formed. Therefore, understanding the properties of nucleus and pre-nucleation events will be significant in reducing the existing knowledge–gap in AD pathogenesis. In this report, we have determined the plausible range of critical nucleation number (n*), the number of monomers associated within the nucleus for a homogenous aggregation model with single unique nucleation event, by two independent methods: A reduced-order stability analysis and ordinary differential equation based numerical analysis, supported by experimental biophysics. The results establish that the most likely range of n* is between 7 and 14 and within, this range, n* = 12 closely supports the experimental data. These numbers are in agreement with those previously reported, and importantly, the report establishes a new modeling framework using two independent approaches towards a convergent solution in modeling complex aggregation reactions. Our model also suggests that the formation of large protofibrils is dependent on the nature of n*, further supporting the idea that pre-nucleation events are significant in controlling the fate of larger aggregates formed. This report has re-opened an old problem with a new perspective and holds promise towards revealing the molecular events in amyloid pathologies in the future.

Protein aggregate turbidity: Simulation of turbidity profiles for mixed-aggregation reactions

Due to their colloidal nature, all protein aggregates scatter light in the visible wavelength region when formed in aqueous solution. This phenomenon makes solution turbidity, a quantity proportional to the relative loss in forward intensity of scattered light, a convenient method for monitoring protein aggregation in biochemical assays. Although turbidity is often taken to be a linear descriptor of the progress of aggregation reactions, this assumption is usually made without performing the necessary checks to provide it with a firm underlying basis. In this article, we outline utilitarian methods for simulating the turbidity generated by homogeneous and mixed-protein aggregation reactions containing fibrous, amorphous, and crystalline structures. The approach is based on a combination of Rayleigh–Gans–Debye theory and approximate forms of the Mie scattering equations.

Aggregate formation and suspension culture of human pluripotent stem cells and differentiated progeny

Culture of human pluripotent stem cells (hPSC) as in vitro multicellular aggregates has been increasingly used as a method to model early embryonic development. Three-dimensional assemblies of hPSCs facilitate interactions between cells and their microenvironment to promote morphogenesis, analogous to the multicellular organization that accompanies embryogenesis. In this paper, we describe a method for reproducibly generating and maintaining populations of homogeneous three-dimensional hPSC aggregates using forced aggregation and rotary orbital suspension culture. We propose solutions to several challenges associated with the consistent formation and extended culture of cell spheroids generated from hPSCs and their differentiated progeny. Further, we provide examples to demonstrate how aggregation can be used as a tool to select specific subpopulations of cells to create homotypic spheroids, or as a means to introduce multiple cell types to create heterotypic tissue constructs. Finally, we demonstrate that the aggregation and rotary suspension method can be used to support culture and maintenance of hPSC-derived cell populations representing each of the three germ layers, underscoring the utility of this platform for culturing many different cell types.

Influence of heat treatment on the structural and optical properties of SrGd2O4:Eu3+ phosphor

Novel red emitting Eu3+ doped SrGd2O4 phosphors were synthesized by homogeneous precipitation method followed by a subsequent combustion process at various temperatures. A systematic study on the consequent structural evolution and optical properties were investigated as a function of various processing temperatures. With the enhancement of processing temperature, SrGd2O4 phosphor showed a gradual transformation from a mixed phase to monophasic nature, with minimized volatile impurities. The microscopic images exhibited homogeneous aggregates of varying shapes and sizes with an average length of about 0.5–5 μm. Eu3+ doped SrGd2O4 phosphors prepared at low temperatures, showed miserably low values of red emission upon UV excitation owing to the presence of volatile impurities. The SrGd2O4:Eu3+ phosphors prepared at relatively high temperature exhibited strong red-orange emissions due to homogeneously occupied Eu3+ ions in the host lattice. The dominant red to orange (R/O) emission intensity ratios and CIE parameters of Eu3+ ions substantiated the site occupation of higher asymmetry sites of Gd3+ ions and the strong covalent nature. Dexter theory and critical distance calculation suggested that the dipole-dipole interaction could be responsible for the concentration quenching of Eu3+ (4 mol.%) doped SrGd2O4 phosphors. Elevated physical and chemical durability and stable photoluminescence made these phosphors suitable for white LEDs and other display applications.

Synthesis and Photocatalytic Activity of Silica-based Sand Quartz as the Supporting TiO2 Photocatalyst

TiO2-SiO2 photocatalyst was prepared by immobilizing TiO2 on natural quartz sand SiO2. The Scanning Electron Microscope-Energy-Dispersive X-ray Spectroscopy (SEM-EDS) and X-Ray Diffraction (XRD) were used to characterize the morphology and structure of the photocatalyst. The photocatalytic activity of the synthesized catalyst was evaluated by applying the catalyst for photocatalytic decomposition of chromium (VI). The concentration of chromium (VI) before and after the photocatalytic decomposition was determined using atomic absorption spectroscopy (AAS). SEM-EDS results of TiO2-SiO2 photocatalyst showed homogenous aggregate. XRD characterization result of the synthesized catalyst showed that TiO2 was in anatase crystalline state, while SiO2 was in amorphous state. The results of the present study indicate that 20% (w/w) TiO2-SiO2 photocatalyst has the highest activity by reducing 92.24% chromium (VI) in the photocatalytic decomposition test.

Robust Aggregator Design for Industrial Thermal Energy Storages in Smart Grid

Exploitation of flexible consumption in the future smart grid requires new actors and infrastructure. In this paper, we propose a hierarchical setup in which a central controller, a so-called “aggregator,” is responsible for managing the flexibilities of industrial thermal loads via a contract-based direct control policy. The aggregator manipulates the consumption profile in an optimal and robust manner in order to provide upward and downward regulating power services. To this end, we consider a robust model predictive control design at the aggregator. The performance of the proposed controller is evaluated by simulating specific case studies involving a supermarket refrigeration system and a heating, ventilation, and air conditioning chiller in conjunction with an ice storage. In addition, we provide a comparison between heterogeneous and homogeneous aggregation of different thermal loads through simulation examples.

Specific Interactions of Ag+ Ions with Anionic Polyacrylate Chains in Dilute Solution

A detailed light scattering investigation is presented on dilute solutions of two long-chain sodium polyacrylates (NaPA) in the presence of monovalent Ag+ ions in 0.01 M NaNO3 aqueous solution at a pH of 9. The relevance for the investigation is based on two features: (i) despite its monovalency, Ag+ is expected to exhibit a much more complex interaction pattern with NaPA than salts based on alkaline cations do; (ii) aqueous solutions of AgNO3 nucleate Ag–nanoparticle formation in the presence of NaPA under UV light, which may be modulated by the solution behavior. Our study revealed the following results. Addition of a low amount of Ag+ ions leads to an aggregation of PA-chains without considerable coil shrinking. At a ratio of silver ions per monomer of 0.001 ≤ [Ag+]/[COO–] ≤ 0.05, combined static and dynamic light scattering (SLS/DLS) suggests formation of homogeneous low density aggregates. Further increase of the Ag+ ion concentration results in a formation of dense unstable aggregates. At ratios of ...

Cistos epidermais em ovinos

São descritos os aspectos clínico-patológicos de cistos epidermais em quatro ovinos, com idade entre dois e 12 anos, oriundos da região central do Rio Grande do Sul, Brasil. Três desses ovinos apresentavam múltiplos nódulos cutâneos, distribuídos aleatoriamente pelo corpo, e um ovino apresentava nódulo cutâneo solitário na região cervical. O período entre o aparecimento do primeiro nódulo e o surgimento de múltiplos nódulos foi de oito meses, em um caso, e um ano, em dois casos. Os quatro ovinos eram os únicos animais afetados em seus respectivos rebanhos. Os nódulos cutâneos eram redondos ou ovais, salientes, flutuantes, não pruriginosos e recobertos por pele parcialmente alopécica. Esses nódulos variavam de 1,0 a 7,0cm de diâmetro e, ocasionalmente, apresentavam um pequeno orifício central, com 1-2mm de diâmetro, na superfície externa. Ao corte eram císticos, delimitados por uma parede fina e branca, com 0,5-0,8cm de espessura, e preenchidos por material branco ou amarelado e friável. Histologicamente, os cistos eram revestidos por epitélio, contendo todos os estratos de um epitélio escamosos estratificado, sobre uma fina cápsula de tecido conjuntivo fibroso denso. Os cistos eram preenchidos por agregados homogêneos e feixes de ceratina, arranjados de forma concêntrica. Baseado na localização e características macroscópicas e histológicas esses cistos foram diagnosticados como cistos epidermais infundibulares.

Analogy between homogeneous and heterogeneous catalysis by subnanometer metal clusters: Ethylene oxidation on Ag trimers supported on MgO(1 0 0)

An analogy between homogeneous catalysis and heterogeneous catalysis by very small, subnanometer-size metal clusters (or heterogeneous ultrananocatalysis) is proposed. We start from the idea that the catalytically active species in heterogeneous ultrananocatalysis are ligand/cluster/support complexes generated in situ under reaction conditions in the high coverage régime, and make a parallel between such species and the metal complexes of homogeneous catalysis. To this aim, we use first-principles simulations and focus on a specific example selecting as catalytic complex a Ag3(CO3)/MgO(100) compound which has been suggested to form during the CO oxidation reaction catalyzed by silver trimer (Ag3) deposited on the regular MgO(100) surface. We investigate whether such a complex can be used as a catalyst in a different reaction: the partial oxidation of ethylene to ethylene oxide (or EtOx reaction). The EtOx catalytic cycle over Ag3(CO3)/MgO(100) is determined, and it is found that it presents an overall reaction energy barrier of 0.9eV. A detailed Molecular Orbital (MO), charge and fragment analysis is then conducted on the species involved in the catalytic cycle, highlighting the similarities of the given catalytic chemistry with homogeneous analogues. The proposed analogy between homogeneous and heterogeneous catalytic aggregates seems promising to widen the spectrum of heterogeneous catalyst design and realize synergistic investigations with accumulated knowledge on homogeneous systems.

Phase separation of aqueous poly(2-dimethylaminoethyl methacrylate-block-N-vinylcaprolactams).

Details of the phase separation of the poly(N-vinylcaprolactam) (PVCL) homopolymers and block copolymers of PVCL and poly(2-dimethylaminoethyl methacrylate) (PDMAEMA) were studied in aqueous buffer solutions. Phase separation occurred at either one or two temperatures depending on pH. The lower critical solution temperature of PVCL can be fine-tuned by varying the molecular weight of the block, whereas the phase separation temperature of the PDMAEMA block is strongly dependent on pH. The enthalpies of the collapse of the PVCL homopolymer and PVCL-b-PDMAEMA block copolymers were measured and show that the blocks phase separate independently upon heating. PVCL is known to bind amphiphilic cations, and correspondingly, according to light scattering, the block copolymers dissolve as single molecules but also form aggregates at room temperature. At temperatures above the cloud points of both blocks, only homogeneous large aggregates were observed. Zeta potential measurements confirmed that, upon heating, PDMAEMA blocks turn out from the collapsed PVCL globule toward the aqueous phase.

Importance of heterogeneous aggregation for NP fate in natural and engineered systems

The growing interest in nanoparticles (NP) is inevitably translating into an increase of their emissions in the environment. On the other hand, the necessary knowledge about the fate and transport of these NPs in the environment remains limited. In particular it is critically important to understand how the interactions of NPs with the particles already present in environmental matrices affect their fate, transport, and eventually persistence in the environment.In this study we present a computer model that expands upon the existing simple homogeneous aggregation models to account for heterogeneous aggregation between NPs and the distribution of natural particles already present in environmental waters. The model follows the concentrations of purely nanoparticle aggregates, purely background particles aggregates, and mixed aggregates, as well as the composition of mixed aggregates. After analytical evaluation, we ran simulations to illustrate the complexity of heterogeneous aggregation and its impact on the fate of NPs.The model predicts that the impact of NP size on their persistence in the environment is accentuated for low affinity between NPs and background particles, and for low background particle concentration.

Influence of Recycled Aggregate on the Rheological Behavior of Cement Mortar

In this work it was studied the influence of recycled fine aggregate obtained from construction and demolition waste (CDW) on the rheological properties of Portland cement mortars. The CDW was initially separate in their main constituents (mortar, ceramic and concrete debris) at the laboratory and then grinded separately to the sand size in order to generate more homogeneous fine aggregates. The characterization of the natural and recycled sands was carried out through physical tests, X-ray diffraction, scanning electron microscopy (SEM), and image analysis (shape and texture description parameters). A conventional mortar and three mortars containing recycled sands were produced with a sand/cement ratio of 4 and consistency index of 255±5 mm. The consistency was kept constant by ranging the water-cement ratio from 0.58 to 1.14. The rheological study was performed using a rotating viscometer to obtain torque-rotation ratio and to calculate the yield stress and plastic viscosity. The results indicate that the presence of recycled aggregate causes a lowering of both yield stress and plastic viscosity with respect to the mortar containing natural aggregate.