1,220 research outputs found
The RHMC Algorithm for 2 Flavours of Dynamical Staggered Fermions
We describe an implementation of the Rational Hybrid Monte Carlo (RHMC)
algorithm for dynamical computations with two flavours of staggered quarks. We
discuss several variants of the method, the performance and possible sources of
error for each of them, and we compare the performance and results to the
inexact R algorithm.Comment: Lattice2003(machine) 3 pages, 1 figure. Added referenc
ABA triblock copolymers: from controlled synthesis to controlled function
The ABA amphiphilic block copolymers, poly(hydroxyethyl methacrylate-hlock-methylphenylsilane-block-hydroxyethyl methacrylate) (PHEMA-PMPS-PHEMA) and poly[oligo(ethylene glycol) methyl ether methacrylate-block-methylphenylsilane-block-oligo(ethylene glycol). methyl ether methacrylate] (POEGMA-PMPS-POEGMA) were successfully synthesised via atom transfer radical polymerisation (ATRP). Macroinitiators suitable for the ATRP of oligo(ethylene glycol) methyl ether methacrylate and 2-hydroxyethyl methacrylate were synthesised from the condensation reaction of alpha,omega-dihalopolymethylphenylsilane and 2'-hydroxyethyl 2-bromo-2-methylpropanoate. The copolymers were characterised using H-1 NMR and C-13 NMR spectroscopy and molecular weight characteristics were determined using size exclusion chromatography and H-1 NMR. The aggregation behaviour of some of the copolymers in water was studied using transmission and scanning electron microscopy and dynamic light scattering. These revealed the prevalent aggregate species to be micelles. Larger aggregates of 300-1000 nm diameter were also observed. The UV induced degradation of the aggregates was studied by UV-Vis spectroscopy. The thermal behaviour of selected copolymers was studied by differential scanning calorimetry and microphase separation of the two components was demonstrated
Utilização de Inteligência Artificial para Análise e Dimensionamento de Estruturas em Concreto Armado: uma prospecção tecnológica
Artificial Intelligence (AI) is a technology that makes use of machines that learn from experience and have the ability to perform complex tasks such as the design of reinforced concrete structures. The increase in the complexity of structures used in constructions brings the need for the development and implementation of new technologies in civil construction. Thus, the objective of this work was to carry out a scientific and technological prospection on the use of AI in the analysis and design of reinforced concrete structures. This work presents a qualitative-quantitative approach, of an exploratory nature, through scientific research in the bases of Capes and Web of Science, and patents in the bases of INPI and Orbit. Although the use of ICTs in civil construction is timid, the prospection pointed to a relevant growth in the use of AI in civil construction in the world, however, in Brazil the use of technology is still very incipient.A Inteligência Artificial (IA) é uma tecnologia que faz uso de máquinas que aprendem com a experiência e possuem a capacidade de executar tarefas complexas como o dimensionamento de estruturas de concreto armado. O aumento na complexibilidade das estruturas utilizadas nas construções traz a necessidade de desenvolvimento e de implantação de novas tecnologias na construção civil. Assim, o objetivo deste trabalho é realizar uma prospecção científica e tecnológica sobre a utilização de IA na análise e no dimensionamento de estruturas em concreto armado. Este trabalho apresenta uma abordagem quali-quantitativa, de natureza exploratória, por meio de pesquisas científicas nas bases da Capes e Web of Science, e patentárias nas bases do INPI e do Orbit. Apesar de o uso de TICs na construção civil ser tímido, a prospecção apontou um crescimento relevante da utilização da IA na construção civil no mundo, no entanto, no Brasil, a utilização dessa tecnologia ainda é muito incipiente
Field theoretic study of bilayer membrane fusion: I. Hemifusion mechanism
Self-consistent field theory is used to determine structural and energetic
properties of metastable intermediates and unstable transition states involved
in the standard stalk mechanism of bilayer membrane fusion. A microscopic model
of flexible amphiphilic chains dissolved in hydrophilic solvent is employed to
describe these self-assembled structures. We find that the barrier to formation
of the initial stalk is much smaller than previously estimated by
phenomenological theories. Therefore its creation it is not the rate limiting
process. The barrier which is relevant is associated with the rather limited
radial expansion of the stalk into a hemifusion diaphragm. It is strongly
affected by the architecture of the amphiphile, decreasing as the effective
spontaneous curvature of the amphiphile is made more negative. It is also
reduced when the tension is increased. At high tension the fusion pore, created
when a hole forms in the hemifusion diaphragm, expands without bound. At very
low membrane tension, small fusion pores can be trapped in a flickering
metastable state. Successful fusion is severely limited by the architecture of
the lipids. If the effective spontaneous curvature is not sufficiently
negative, fusion does not occur because metastable stalks, whose existence is a
seemingly necessary prerequisite, do not form at all. However if the
spontaneous curvature is too negative, stalks are so stable that fusion does
not occur because the system is unstable either to a phase of stable radial
stalks, or to an inverted-hexagonal phase induced by stable linear stalks. Our
results on the architecture and tension needed for successful fusion are
summarized in a phase diagram.Comment: in press, Biophys.J. accepted versio
Nuclear rupture at sites of high curvature compromises retention of DNA repair factors.
The nucleus is physically linked to the cytoskeleton, adhesions, and extracellular matrix-all of which sustain forces, but their relationships to DNA damage are obscure. We show that nuclear rupture with cytoplasmic mislocalization of multiple DNA repair factors correlates with high nuclear curvature imposed by an external probe or by cell attachment to either aligned collagen fibers or stiff matrix. Mislocalization is greatly enhanced by lamin A depletion, requires hours for nuclear reentry, and correlates with an increase in pan-nucleoplasmic foci of the DNA damage marker γH2AX. Excess DNA damage is rescued in ruptured nuclei by cooverexpression of multiple DNA repair factors as well as by soft matrix or inhibition of actomyosin tension. Increased contractility has the opposite effect, and stiff tumors with low lamin A indeed exhibit increased nuclear curvature, more frequent nuclear rupture, and excess DNA damage. Additional stresses likely play a role, but the data suggest high curvature promotes nuclear rupture, which compromises retention of DNA repair factors and favors sustained damage
Spatial organization acts on cell signaling: how physical force contributes to the development of cancer
Cells constantly encounter physical forces and respond to neighbors and circulating factors by triggering intracellular signaling cascades that in turn affect their behavior. The mechanisms by which cells transduce mechanical signals to downstream biochemical changes are not well understood. In their work, Salaita and coworkers show that the spatial organization of cell surface receptors is crucial for mechanotransduction. Consequently, force modulation that disrupts the mechanochemical coupling may represent a critical step in cancerogenesis
Matrix stiffening sensitizes epithelial cells to EGF and enables the loss of contact inhibition of proliferation
Anchorage to a compliant extracellular matrix (ECM) and contact with neighboring cells impose important constraints on the proliferation of epithelial cells. How anchorage and contact dependence are inter-related and how cells weigh these adhesive cues alongside soluble growth factors to make a net cell cycle decision remain unclear. Here, we show that a moderate 4.5-fold stiffening of the matrix reduces the threshold amount of epidermal growth factor (EGF) needed to over-ride contact inhibition by over 100-fold. At EGF doses in the range of the dissociation constant (Kd) for ligand binding, epithelial cells on soft matrices are contact inhibited with DNA synthesis restricted to the periphery of cell clusters. By contrast, on stiff substrates, even EGF doses at sub-Kd levels over-ride contact inhibition, leading to proliferation throughout the cluster. Thus, matrix stiffening significantly sensitizes cells to EGF, enabling contact-independent spatially uniform proliferation. Contact inhibition on soft substrates requires E-cadherin, and the loss of contact inhibition upon matrix stiffening is accompanied by the disruption of cell–cell contacts, changes in the localization of the EGF receptor and ZO-1, and selective attenuation of ERK, but not Akt, signaling. We propose a quantitative framework for the epigenetic priming (via ECM stiffening) of a classical oncogenic pathway (EGF) with implications for the regulation of tissue growth during morphogenesis and cancer progression
The Interplay between Chemistry and Mechanics in the Transduction of a Mechanical Signal into a Biochemical Function
There are many processes in biology in which mechanical forces are generated.
Force-bearing networks can transduce locally developed mechanical signals very
extensively over different parts of the cell or tissues. In this article we
conduct an overview of this kind of mechanical transduction, focusing in
particular on the multiple layers of complexity displayed by the mechanisms
that control and trigger the conversion of a mechanical signal into a
biochemical function. Single molecule methodologies, through their capability
to introduce the force in studies of biological processes in which mechanical
stresses are developed, are unveiling subtle intertwining mechanisms between
chemistry and mechanics and in particular are revealing how chemistry can
control mechanics. The possibility that chemistry interplays with mechanics
should be always considered in biochemical studies.Comment: 50 pages, 18 figure
Adhesion of membranes via receptor-ligand complexes: Domain formation, binding cooperativity, and active processes
Cell membranes interact via anchored receptor and ligand molecules. Central
questions on cell adhesion concern the binding affinity of these
membrane-anchored molecules, the mechanisms leading to the receptor-ligand
domains observed during adhesion, and the role of cytoskeletal and other active
processes. In this review, these questions are addressed from a theoretical
perspective. We focus on models in which the membranes are described as elastic
sheets, and the receptors and ligands as anchored molecules. In these models,
the thermal membrane roughness on the nanometer scale leads to a cooperative
binding of anchored receptor and ligand molecules, since the receptor-ligand
binding smoothens out the membranes and facilitates the formation of additional
bonds. Patterns of receptor domains observed in Monte Carlo simulations point
towards a joint role of spontaneous and active processes in cell adhesion. The
interactions mediated by the receptors and ligand molecules can be
characterized by effective membrane adhesion potentials that depend on the
concentrations and binding energies of the molecules.Comment: Review article, 13 pages, 9 figures, to appear in Soft Matte
- …