102 research outputs found
Anisotropic spatially heterogeneous dynamics in a model glass-forming binary mixture
We calculated a four-point correlation function G_4(k,r;t) and the
corresponding structure factor S_4(k,q;t) for a model glass-forming binary
mixture. These functions measure the spatial correlations of the relaxation of
different particles. We found that these four-point functions are anisotropic
and depend on the angle between vectors k and r (or q). The anisotropy is the
strongest for times somewhat longer than the beta relaxation time but it is
quite pronounced even for times comparable to the alpha relaxation time,
tau_alpha. At the lowest temperatures S_4(k,q;tau_alpha) is strongly
anisotropic even for the smallest wavevector q accessible in our simulation
On the construction of explosive relation algebras
Fork algebras are an extension of relation algebras obtained by extending the
set of logical symbols with a binary operator called fork. This class of
algebras was introduced by Haeberer and Veloso in the early 90's aiming at
enriching relation algebra, an already successful language for program
specification, with the capability of expressing some form of parallel
computation.
The further study of this class of algebras led to many meaningful results
linked to interesting properties of relation algebras such as representability
and finite axiomatizability, among others. Also in the 90's, Veloso introduced
a subclass of relation algebras that are expansible to fork algebras, admitting
a large number of non-isomorphic expansions, referred to as explosive relation
algebras.
In this work we discuss some general techniques for constructing algebras of
this type
Single-charge escape processes through a hybrid turnstile in a dissipative environment
We have investigated the static, charge-trapping properties of a hybrid
superconductor---normal metal electron turnstile embedded into a high-ohmic
environment. The device includes a local Cr resistor on one side of the
turnstile, and a superconducting trapping island on the other side. The
electron hold times, t ~ 2-20s, in our two-junction circuit are comparable with
those of typical multi-junction, N >= 4, normal-metal single-electron tunneling
devices. A semi-phenomenological model of the environmental activation of
tunneling is applied for the analysis of the switching statistics. The
experimental results are promising for electrical metrology.Comment: Submitted to New Journal of Physics 201
A type III complement factor D deficiency: Structural insights for inhibition of the alternative pathway.
Abstract
Background: Complement factor D (FD) is the rate-limiting enzyme of the alternative complement pathway. Previous reports of FD deficiency featured absent plasma FD (type I deficiency) and susceptibility to meningococcal infection. A new FD mutant, which is non-functional but fully expressed, was identified in a patient with invasive meningococcal disease.
Objectives: We sought to investigate the molecular features of this novel FD mutant.
Methods: We performed complement haemolytic assays, western blot analysis of serum FD and Sanger sequencing of the CFD gene. Recombinant mutant FD was assessed by in vitro catalytic assays, circular dichroism, thermal shift assays, esterolytic assays and surface plasmon resonance. Molecular dynamics simulation was used to visualise the structural changes in mutant FD.
Results: A homozygous single-nucleotide variation of the CFD gene in the patient and their sibling resulted in an arginine to proline (R176P) substitution in FD. While R176P FD was stable and fully expressed in blood, it had minimal catalytic activity. Mutation R176P caused key FD-C3bB binding exosite loop 156-162 to lose its binding-competent conformation and stabilised the inactive conformation of FD. Consequently, R176P FD was unable to bind its natural substrate, C3bB. Neither patient nor sibling demonstrated the glucose homeostasis impairment that occurs in FD-null mice.
Conclusions: Here, we report the first genetically confirmed functional, or type III, deficiency of an activating complement serine protease. This novel mechanism of FD inhibition can inform further development of alternative pathway inhibitors to treat common inflammatory diseases such as age-related macular degeneration
The multiple faces of self-assembled lipidic systems
Lipids, the building blocks of cells, common to every living organisms, have the propensity to self-assemble into well-defined structures over short and long-range spatial scales. The driving forces have their roots mainly in the hydrophobic effect and electrostatic interactions. Membranes in lamellar phase are ubiquitous in cellular compartments and can phase-separate upon mixing lipids in different liquid-crystalline states. Hexagonal phases and especially cubic phases can be synthesized and observed in vivo as well. Membrane often closes up into a vesicle whose shape is determined by the interplay of curvature, area difference elasticity and line tension energies, and can adopt the form of a sphere, a tube, a prolate, a starfish and many more. Complexes made of lipids and polyelectrolytes or inorganic materials exhibit a rich diversity of structural morphologies due to additional interactions which become increasingly hard to track without the aid of suitable computer models. From the plasma membrane of archaebacteria to gene delivery, self-assembled lipidic systems have left their mark in cell biology and nanobiotechnology; however, the underlying physics is yet to be fully unraveled
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