168 research outputs found
Revealing the pure confinement effect in glass-forming liquids by dynamic mechanical analysis
Many molecular glass forming liquids show a shift of the glass transition Tg
to lower temperatures when the liquid is confined into mesoporous host
matrices. Two contrary explanations for this effect are given in literature:
First, confinement induced acceleration of the dynamics of the molecules leads
to an effective downshift of Tg increasing with decreasing pore size. Secondly,
due to thermal mismatch between the liquid and the surrounding host matrix,
negative pressure develops inside the pores with decreasing temperature, which
also shifts Tg to lower temperatures. Here we present novel dynamic mechanical
analysis measurements of the glass forming liquid salol in Vycor and Gelsil
with pore sizes of d = 2.6, 5.0 and 7.5 nm. The dynamic complex elastic
susceptibility data can be consistently described with the assumption of two
relaxation processes inside the pores: A surface induced slowed down relaxation
due to interaction with rough pore interfaces and a second relaxation within
the core of the pores. This core relaxation time is reduced with decreasing
pore size d, leading to a downshift of Tg in perfect agreement with recent DSC
measurements
Are there Local Minima in the Magnetic Monopole Potential in Compact QED?
We investigate the influence of the granularity of the lattice on the
potential between monopoles. Using the flux definition of monopoles we
introduce their centers of mass and are able to realize continuous shifts of
the monopole positions. We find periodic deviations from the -behavior of
the monopole-antimonopole potential leading to local extrema. We suppose that
these meta-stabilities may influence the order of the phase transition in
compact QED.Comment: 11 pages, 5 figure
Confinement effects on glass forming liquids probed by DMA
Many molecular glass forming liquids show a shift of the glass transition T-g
to lower temperatures when the liquid is confined into mesoporous host
matrices. Two contrary explanations for this effect are given in literature:
First, confinement induced acceleration of the dynamics of the molecules leads
to an effective downshift of T-g increasing with decreasing pore size. Second,
due to thermal mismatch between the liquid and the surrounding host matrix,
negative pressure develops inside the pores with decreasing temperature, which
also shifts T-g to lower temperatures. Here we present dynamic mechanical
analysis measurements of the glass forming liquid salol in Vycor and Gelsil
with pore sizes of d=2.6, 5.0 and 7.5 nm. The dynamic complex elastic
susceptibility data can be consistently described with the assumption of two
relaxation processes inside the pores: A surface induced slowed down relaxation
due to interaction with rough pore interfaces and a second relaxation within
the core of the pores. This core relaxation time is reduced with decreasing
pore size d, leading to a downshift of T-g proportional to 1/d in perfect
agreement with recent differential scanning calorimetry (DSC) measurements.
Thermal expansion measurements of empty and salol filled mesoporous samples
revealed that the contribution of negative pressure to the downshift of T-g is
small (<30%) and the main effect is due to the suppression of dynamically
correlated regions of size xi when the pore size xi approaches
Finite strain Landau theory of high pressure phase transformations
The properties of materials near structural phase transitions are often
successfully described in the framework of Landau theory. While the focus is
usually on phase transitions, which are induced by temperature changes
approaching a critical temperature T-c, here we will discuss structural phase
transformations driven by high hydrostatic pressure, as they are of major
importance for understanding processes in the interior of the earth. Since at
very high pressures the deformations of a material are generally very large,
one needs to apply a fully nonlinear description taking physical as well as
geometrical nonlinearities (finite strains) into account. In particular it is
necessary to retune conventional Landau theory to describe such phase
transitions. In Troster et al (2002 Phys. Rev. Lett. 88 55503) we constructed a
Landau-type free energy based on an order parameter part, an order
parameter-(finite) strain coupling and a nonlinear elastic term. This model
provides an excellent and efficient framework for the systematic study of phase
transformations for a wide range of materials up to ultrahigh pressures
GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals
The synaptic connection from medial habenula (MHb) to interpeduncular nucleus (IPN) is critical for emotion-related behaviors and uniquely expresses R-type Ca2+ channels (Cav2.3) and auxiliary GABAB receptor (GBR) subunits, the K+-channel tetramerization domain-containing proteins (KCTDs). Activation of GBRs facilitates or inhibits transmitter release from MHb terminals depending on the IPN subnucleus, but the role of KCTDs is unknown. We therefore examined the localization and function of Cav2.3, GBRs, and KCTDs in this pathway in mice. We show in heterologous cells that KCTD8 and KCTD12b directly bind to Cav2.3 and that KCTD8 potentiates Cav2.3 currents in the absence of GBRs. In the rostral IPN, KCTD8, KCTD12b, and Cav2.3 co-localize at the presynaptic active zone. Genetic deletion indicated a bidirectional modulation of Cav2.3-mediated release by these KCTDs with a compensatory increase of KCTD8 in the active zone in KCTD12b-deficient mice. The interaction of Cav2.3 with KCTDs therefore scales synaptic strength independent of GBR activation
Potentials of Mean Force for Protein Structure Prediction Vindicated, Formalized and Generalized
Understanding protein structure is of crucial importance in science, medicine
and biotechnology. For about two decades, knowledge based potentials based on
pairwise distances -- so-called "potentials of mean force" (PMFs) -- have been
center stage in the prediction and design of protein structure and the
simulation of protein folding. However, the validity, scope and limitations of
these potentials are still vigorously debated and disputed, and the optimal
choice of the reference state -- a necessary component of these potentials --
is an unsolved problem. PMFs are loosely justified by analogy to the reversible
work theorem in statistical physics, or by a statistical argument based on a
likelihood function. Both justifications are insightful but leave many
questions unanswered. Here, we show for the first time that PMFs can be seen as
approximations to quantities that do have a rigorous probabilistic
justification: they naturally arise when probability distributions over
different features of proteins need to be combined. We call these quantities
reference ratio distributions deriving from the application of the reference
ratio method. This new view is not only of theoretical relevance, but leads to
many insights that are of direct practical use: the reference state is uniquely
defined and does not require external physical insights; the approach can be
generalized beyond pairwise distances to arbitrary features of protein
structure; and it becomes clear for which purposes the use of these quantities
is justified. We illustrate these insights with two applications, involving the
radius of gyration and hydrogen bonding. In the latter case, we also show how
the reference ratio method can be iteratively applied to sculpt an energy
funnel. Our results considerably increase the understanding and scope of energy
functions derived from known biomolecular structures
Annexin A2 antibodies but not inhibitors of the annexin A2 heterotetramer impair productive HIV-1 infection of macrophages in vitro
During sexual transmission of human immunodeficiency virus (HIV), macrophages are initial targets for HIV infection. Secretory leukocyte protease inhibitor (SLPI) has been shown to protect against HIV infection of macrophages through interactions with annexin A2 (A2), which is found on the macrophage cell surface as a heterotetramer (A2t) consisting of A2 and S100A10. Therefore, we investigated potential protein-protein interactions between A2 and HIV-1 gp120 through a series of co-immunoprecipitation assays and a single molecule pulldown (SiMPull) technique. Additionally, inhibitors of A2t (A2ti) that target the interaction between A2 and S100A10 were tested for their ability to impair productive HIV-1 infection of macrophages. Our data suggest that interactions between HIV-1 gp120 and A2 exist, though this interaction may be indirect. Furthermore, an anti-A2 antibody impaired HIV-1 particle production in macrophages in vitro, whereas A2ti did not indicating that annexin A2 may promote HIV-1 infection of macrophages in its monomeric rather than tetrameric form
The Intracellular Virus-Containing Compartments in Primary Human Macrophages Are Largely Inaccessible to Antibodies and Small Molecules
HIV-1 assembly and release occurs at the plasma membrane of human T lymphocytes and model epithelial cell lines, whereas in macrophages intracellular sites of virus assembly or accumulation predominate. The origin of the intracellular virus-containing compartment (VCC) has been controversial. This compartment is enriched in markers of the multivesicular body, and has been described as a modified endosomal compartment. Several studies of this compartment have revealed the presence of small channels connecting to the plasma membrane, suggesting that instead of an endosomal origin the compartment is a modified plasma membrane compartment. If the compartment is accessible to the external environment, this would have important implications for antiviral immune responses and antiviral therapy. We performed a series of experiments designed to determine if the VCC in macrophages was open to the external environment and accessible to antibodies and small molecules. The majority of VCCs were found to be inaccessible to exogenously-applied antibodies to tetraspanins in the absence of membrane permeabilization, while tetraspanin staining was readily observed following membrane permeabilization. Cationized ferritin was utilized to stain the plasma membrane, and revealed that the majority of virus-containing compartments were inaccessible to ferritin. Low molecular weight dextrans could access only a very small percentage of VCCs, and these tended to be more peripheral compartments. We conclude that the VCCs in monocyte-derived human macrophages are heterogeneous, but the majority of VCCs are closed to the external environment
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