767 research outputs found
A Spatio-Temporal Model Reveals Self-Limiting FcɛRI Cross-Linking by Multivalent Antigens
Aggregation of cell surface receptor proteins by multivalent antigens is an essential early step for immune cell signalling. A number of experimental and modelling studies in the past have investigated multivalent ligand-mediated aggregation of IgE receptors (FcɛRI) in the plasma membrane of mast cells. However, understanding of the mechanisms of FcɛRI aggregation remains incomplete. Experimental reports indicate that FcɛRI forms relatively small and finite-sized clusters when stimulated by a multivalent ligand. By contrast, modelling studies have shown that receptor cross-linking by a trivalent ligand may lead to the formation of large receptor superaggregates that may potentially give rise to hyperactive cellular responses. In this work, we have developed a Brownian dynamics-based spatio-temporal model to analyse FcɛRI aggregation by a trivalent antigen. Unlike the existing models, which implemented non-spatial simulation approaches, our model explicitly accounts for the coarse-grained site-specific features of the multivalent species (molecules and complexes). The model incorporates membrane diffusion, steric collisions and sub-nanometre-scale site-specific interaction of the time-evolving species of arbitrary structures. Using the model, we investigated temporal evolution of the species and their diffusivities. Consistent with a recent experimental report, our model predicted sharp decay in species mobility in the plasma membrane in response receptor cross-linking by a multivalent antigen. We show that, due to such decay in the species mobility, post-stimulation receptor aggregation may become self-limiting. Our analysis reveals a potential regulatory mechanism suppressing hyperactivation of immune cells in response to multivalent antigens
Ordering phenomena in quasi one-dimensional organic conductors
Low-dimensional organic conductors could establish themselves as model
systems for the investigation of the physics in reduced dimensions. In the
metallic state of a one-dimensional solid, Fermi-liquid theory breaks down and
spin and charge degrees of freedom become separated. But the metallic phase is
not stable in one dimension: as the temperature is reduced, the electronic
charge and spin tend to arrange themselves in an ordered fashion due to strong
correlations. The competition of the different interactions is responsible for
which broken-symmetry ground state is eventually realized in a specific
compound and which drives the system towards an insulating state.
Here we review the various ordering phenomena and how they can be identified
by optic and magnetic measurements. While the final results might look very
similar in the case of a charge density wave and a charge-ordered metal, for
instance, the physical cause is completely different. When density waves form,
a gap opens in the density of states at the Fermi energy due to nesting of the
one-dimension Fermi surface sheets. When a one-dimensional metal becomes a
charge-ordered Mott insulator, on the other hand, the short-range Coulomb
repulsion localizes the charge on the lattice sites and even causes certain
charge patterns.
We try to point out the similarities and conceptional differences of these
phenomena and give an example for each of them. Particular emphasis will be put
on collective phenomena which are inherently present as soon as ordering breaks
the symmetry of the system.Comment: Review article Naturwissenschaften 200
Carotid Body AT4 Receptor Expression and its Upregulation in Chronic Hypoxia
Hypoxia regulates the local expression of angiotensin-generating system in the rat carotid body and the me-tabolite angiotensin IV (Ang IV) may be involved in the modulation of carotid body function. We tested the hypothesis that Ang IV-binding angiotensin AT4 receptors play a role in the adaptive change of the carotid body in hypoxia. The expression and localization of Ang IV-binding sites and AT4 receptors in the rat carotid bodies were studied with histochemistry. Specific fluorescein-labeled Ang IV binding sites and positive staining of AT4 immunoreactivity were mainly found in lobules in the carotid body. Double-labeling study showed the AT4 receptor was localized in glomus cells containing tyrosine hydroxylase, suggesting the expression in the chemosensitive cells. Intriguingly, the Ang IV-binding and AT4 immunoreactivity were more intense in the carotid body of chronically hypoxic (CH) rats (breathing 10% oxygen for 4 weeks) than the normoxic (Nx) control. Also, the protein level of AT4 receptor was doubled in the CH comparing with the Nx group, supporting an upregulation of the expression in hypoxia. To examine if Ang IV induces intracellular Ca2+ response in the carotid body, cytosolic calcium ([Ca2+]i) was measured by spectrofluorimetry in fura-2-loaded glomus cells dissociated from CH and Nx carotid bodies. Exogenous Ang IV elevated [Ca2+]i in the glomus cells and the Ang IV response was significantly greater in the CH than the Nx group. Hence, hypoxia induces an upregulation of the expression of AT4 receptors in the glomus cells of the carotid body with an increase in the Ang IV-induced [Ca2+]i elevation. This may be an additional pathway enhancing the Ang II action for the activation of chemoreflex in the hypoxic response during chronic hypoxia
Magnetic Catalysis and Quantum Hall Ferromagnetism in Weakly Coupled Graphene
We study the realization in a model of graphene of the phenomenon whereby the
tendency of gauge-field mediated interactions to break chiral symmetry
spontaneously is greatly enhanced in an external magnetic field. We prove that,
in the weak coupling limit, and where the electron-electron interaction
satisfies certain mild conditions, the ground state of charge neutral graphene
in an external magnetic field is a quantum Hall ferromagnet which spontaneously
breaks the emergent U(4) symmetry to U(2)XU(2).
We argue that, due to a residual CP symmetry, the quantum Hall ferromagnet
order parameter is given exactly by the leading order in perturbation theory.
On the other hand, the chiral condensate which is the order parameter for
chiral symmetry breaking generically obtains contributions at all orders. We
compute the leading correction to the chiral condensate. We argue that the
ensuing fermion spectrum resembles that of massive fermions with a vanishing
U(4)-valued chemical potential. We discuss the realization of parity and charge
conjugation symmetries and argue that, in the context of our model, the charge
neutral quantum Hall state in graphene is a bulk insulator, with vanishing
longitudinal conductivity due to a charge gap and Hall conductivity vanishing
due to a residual discrete particle-hole symmetry.Comment: 35 page
Efficient numerical computation and experimental study of temporally long equilibrium scour development around abutment
YesFor the abutment bed scour to reach its equilibrium state, a long flow time is needed. Hence, the
employment of usual strategy of simulating such scouring event using the 3D numerical model is
very time consuming and less practical. In order to develop an applicable model to consider
temporally long abutment scouring process, this study modifies the common approach of 2D
shallow water equations (SWEs) model to account for the sediment transport and turbulence, and
provides a realistic approach to simulate the long scouring process to reach the full scour
equilibrium. Due to the high demand of the 2D SWEs numerical scheme performance to simulate
the abutment bed scouring, a recently proposed surface gradient upwind method (SGUM) was
also used to improve the simulation of the numerical source terms. The abutment scour
experiments of this study were conducted using the facility of Hydraulics Laboratory at Nanyang
Technological University, Singapore to compare with the presented 2D SGUM-SWEs model.
Fifteen experiments were conducted over a total period of 3059.7 hours experimental time (over
4.2 months). The comparison shows that the 2D SGUM-SWEs model gives good representation
to the experimental results with the practical advantage
Solitary waves in the Nonlinear Dirac Equation
In the present work, we consider the existence, stability, and dynamics of
solitary waves in the nonlinear Dirac equation. We start by introducing the
Soler model of self-interacting spinors, and discuss its localized waveforms in
one, two, and three spatial dimensions and the equations they satisfy. We
present the associated explicit solutions in one dimension and numerically
obtain their analogues in higher dimensions. The stability is subsequently
discussed from a theoretical perspective and then complemented with numerical
computations. Finally, the dynamics of the solutions is explored and compared
to its non-relativistic analogue, which is the nonlinear Schr{\"o}dinger
equation. A few special topics are also explored, including the discrete
variant of the nonlinear Dirac equation and its solitary wave properties, as
well as the PT-symmetric variant of the model
TRAIP/RNF206 is required for recruitment of RAP80 to sites of DNA damage
RAP80 localizes to sites of DNA insults to enhance the DNA-damage responses. Here we identify TRAIP/RNF206 as a novel RAP80-interacting protein and find that TRAIP is necessary for translocation of RAP80 to DNA lesions. Depletion of TRAIP results in impaired accumulation of RAP80 and functional downstream partners, including BRCA1, at DNA lesions. Conversely, accumulation of TRAIP is normal in RAP80-depleted cells, implying that TRAIP acts upstream of RAP80 recruitment to DNA lesions. TRAIP localizes to sites of DNA damage and cells lacking TRAIP exhibit classical DNA-damage response-defect phenotypes. Biochemical analysis reveals that the N terminus of TRAIP is crucial for RAP80 interaction, while the C terminus of TRAIP is required for TRAIP localization to sites of DNA damage through a direct interaction with RNF20-RNF40. Taken together, our findings demonstrate that the novel RAP80-binding partner TRAIP regulates recruitment of the damage signalling machinery and promotes homologous recombinationopen
Smoking before the birth of a first child is not associated with increased risk of breast cancer: findings from the British Women's Heart and Health Cohort Study and a meta-analysis
It has been suggested that the period between puberty and first birth is a time when the breast is particularly susceptible to carcinogenic effects. In a cohort of 3047 women aged 60-79 years (N=139 breast cancer cases), we found no association between smoking before the birth of a first child and breast cancer risk: fully adjusted (for age, number of children, age at birth of first child, age at menarche, age at menopausal, hysterectomy and/or oophorectomy, ever use of oral contraception, use of hormone replacement therapy, alcohol consumption, body mass index, childhood and adulthood social class) odds ratio 1.06 (95% confidence interval: 0.72, 1.56). The pooled estimate from a meta-analysis of our study and 11 previously published studies (N=6528 cases) was 1.07 (0.94, 1.22). We conclude that smoking prior to the birth of a first child is not associated with increased risk of breast cancer
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