262 research outputs found
Transitions of tethered polymer chains: A simulation study with the bond fluctuation lattice model
A polymer chain tethered to a surface may be compact or extended, adsorbed or
desorbed, depending on interactions with the surface and the surrounding
solvent. This leads to a rich phase diagram with a variety of transitions. To
investigate these transitions we have performed Monte Carlo simulations of a
bond-fluctuation model with Wang-Landau and umbrella sampling algorithms in a
two-dimensional state space. The simulations' density of states results have
been evaluated for interaction parameters spanning the range from good to poor
solvent conditions and from repulsive to strongly attractive surfaces. In this
work, we describe the simulation method and present results for the overall
phase behavior and for some of the transitions. For adsorption in good solvent,
we compare with Metropolis Monte Carlo data for the same model and find good
agreement between the results. For the collapse transition, which occurs when
the solvent quality changes from good to poor, we consider two situations
corresponding to three-dimensional (hard surface) and two-dimensional (very
attractive surface) chain conformations, respectively. For the hard surface, we
compare tethered chains with free chains and find very similar behavior for
both types of chains. For the very attractive surface, we find the
two-dimensional chain collapse to be a two-step transition with the same
sequence of transitions that is observed for three-dimensional chains: a
coil-globule transition that changes the overall chain size is followed by a
local rearrangement of chain segments.Comment: 17 pages, 12 figures, to appear in J. Chem. Phy
Modulating the Fibrillization of Parathyroid-Hormone (PTH) Peptides: Azo-Switches as Reversible and Catalytic Entities
We here report a novel strategy to control the bioavailability of the fibrillizing parathyroid
hormone (PTH)-derived peptides, where the concentration of the bioactive form is controlled by
an reversible, photoswitchable peptide. PTH1–84, a human hormone secreted by the parathyroid
glands, is important for the maintenance of extracellular fluid calcium and phosphorus homeostasis.
Controlling fibrillization of PTH1–84 represents an important approach for in vivo applications, in
view of the pharmaceutical applications for this protein. We embed the azobenzene derivate 3-{[(4-
aminomethyl)phenyl]diazenyl}benzoic acid (3,40-AMPB) into the PTH-derived peptide PTH25–37 to
generate the artificial peptide AzoPTH25–37 via solid-phase synthesis. AzoPTH25–37 shows excellent
photostability (more than 20 h in the dark) and can be reversibly photoswitched between its cis/trans
forms. As investigated by ThT-monitored fibrillization assays, the trans-form of AzoPTH25–37 fibrillizes
similar to PTH25–37, while the cis-form of AzoPTH25–37 generates only amorphous aggregates.
Additionally, cis-AzoPTH25–37 catalytically inhibits the fibrillization of PTH25–37 in ratios of up to
one-fifth. The approach reported here is designed to control the concentration of PTH-peptides,
where the bioactive form can be catalytically controlled by an added photoswitchable peptide
Mesophase formation in two-component cylindrical bottle-brush polymers
When two types of side chains (A,B) are densely grafted to a (stiff) backbone
and the resulting bottle-brush polymer is in a solution under poor solvent
conditions, an incompatibility between A and B leads to microphase separation
in the resulting cylindrical brush. The possible types of ordering are
reminiscent of the ordering of block copolymers in cylindrical confinement.
Starting from this analogy, Leibler's theory of microphase separation in block
copolymer melts is generalized to derive a description of the system in the
weak segregation limit. Also molecular dynamics simulation results of a
corresponding coarse-grained bead-spring model are presented. Using side chain
lengths up to N = 50 effective monomers, the ratio of the Lennard-Jones energy
parameter between unlike monomers and monomers of the same
kind is varied. Various correlation
functions are analyzed to study the conditions when (local) Janus cylinder-type
ordering and when (local) microphase separation in the direction along the
cylinder axis occurs. Both the analytical theory and the simulations give
evidence for short range order due to a tendency towards microphase separation
in the axial direction, with a wavelength proportional to the side chain
gyration radius, irrespective of temperature and grafting density, for a wide
range of these parameters.Comment: 26 pages, 19 figure
Structure of bottle-brush polymers in solution: A Monte Carlo test of models for the scattering function
Extensive Monte Carlo results are presented for a lattice model of a
bottle-brush polymer under good solvent or Theta solvent conditions. Varying
the side chain length, backbone length, and the grafting density for a rigid
straight backbone, both radial density profiles of monomers and side chain ends
are obtained, as well as structure factors describing the scattering from a
single side chain and from the total bottle-brush polymer. To describe the
structure in the interior of a very long bottle-brush, a periodic boundary
condition in the direction along the backbone is used, and to describe effects
due to the finiteness of the backbone length, a second set of simulations with
free ends of the backbone is performed. In the latter case, the inhomogeneity
of the structure in the direction along the backbone is carefully investigated.
We use these results to test various phenomenological models that have been
proposed to interpret experimental scattering data for bottle-brush
macromolecules. These models aim to extract information on the radial density
profile of a bottle-brush from the total scattering via suitable convolution
approximations. Possibilities to improve such models, guided by our simulation
results, are discussed.Comment: 15 pages, 16 figure
Timescales of self-healing in human bone tissue and polymeric ionic liquids
Strain (stress-free) relaxation in mechanically prestrained bone has a time constant of 75 s. It occurs by a reorganization of the proteoglycan-glycoprotein matrix between collagen fibers, which requires ionic interactions. Dissolving and relinking the ionic bonds is thus an important tool of nature to enable plastic deformation and to develop self-healing tissues. A way to transfer this approach to technical materials is the attachment of ionic end groups to polymeric chains. In these classes of materials, the so-called polymeric ionic liquids, structural recovery of thermally disorganized material is observed. A time constant between minutes and a week could be achieved, also by ionic rearrangement. The same mechanism, rearrangement of ionic bonds, can lead to vastly different relaxation times when the ionic interaction is varied by exchange of the cationic end groups or the anions
Molecular Dynamics Simulations
A tutorial introduction to the technique of Molecular Dynamics (MD) is given,
and some characteristic examples of applications are described. The purpose and
scope of these simulations and the relation to other simulation methods is
discussed, and the basic MD algorithms are described. The sampling of intensive
variables (temperature T, pressure p) in runs carried out in the microcanonical
(NVE) ensemble (N= particle number, V = volume, E = energy) is discussed, as
well as the realization of other ensembles (e.g. the NVT ensemble). For a
typical application example, molten SiO2, the estimation of various transport
coefficients (self-diffusion constants, viscosity, thermal conductivity) is
discussed. As an example of Non-Equilibrium Molecular Dynamics (NEMD), a study
of a glass-forming polymer melt under shear is mentioned.Comment: 38 pages, 11 figures, to appear in J. Phys.: Condens. Matte
Hopping Transport in the Presence of Site Energy Disorder: Temperature and Concentration Scaling of Conductivity Spectra
Recent measurements on ion conducting glasses have revealed that conductivity
spectra for various temperatures and ionic concentrations can be superimposed
onto a common master curve by an appropriate rescaling of the conductivity and
frequency. In order to understand the origin of the observed scaling behavior,
we investigate by Monte Carlo simulations the diffusion of particles in a
lattice with site energy disorder for a wide range of both temperatures and
concentrations. While the model can account for the changes in ionic activation
energies upon changing the concentration, it in general yields conductivity
spectra that exhibit no scaling behavior. However, for typical concentrations
and sufficiently low temperatures, a fairly good data collapse is obtained
analogous to that found in experiment.Comment: 6 pages, 4 figure
Position dependent mismatch discrimination on DNA microarrays – experiments and model
<p>Abstract</p> <p>Background</p> <p>The propensity of oligonucleotide strands to form stable duplexes with complementary sequences is fundamental to a variety of biological and biotechnological processes as various as microRNA signalling, microarray hybridization and PCR. Yet our understanding of oligonucleotide hybridization, in particular in presence of surfaces, is rather limited. Here we use oligonucleotide microarrays made in-house by optically controlled DNA synthesis to produce probe sets comprising all possible single base mismatches and base bulges for each of 20 sequence motifs under study.</p> <p>Results</p> <p>We observe that mismatch discrimination is mostly determined by the defect position (relative to the duplex ends) as well as by the sequence context. We investigate the thermodynamics of the oligonucleotide duplexes on the basis of double-ended molecular zipper. Theoretical predictions of defect positional influence as well as long range sequence influence agree well with the experimental results.</p> <p>Conclusion</p> <p>Molecular zipping at thermodynamic equilibrium explains the binding affinity of mismatched DNA duplexes on microarrays well. The position dependent nearest neighbor model (PDNN) can be inferred from it. Quantitative understanding of microarray experiments from first principles is in reach.</p
Uniform hopping approach to the FM Kondo Model at finite temperature
We study the ferromagnetic Kondo model with classical corespins via unbiased
Monte-Carlo simulations and derive a simplified model for the treatment of the
corespins at any temperature. Our simplified model captures the main aspects of
the Kondo model and can easily be evaluated both numerically and analytically.
It provides a better qualitative understanding of the physical features of the
Kondo model and rationalizes the Monte-Carlo results, including the spectral
density A_k(omega) of a 1D chain with nearest neighbor Coulomb repulsion. By
calculating the specific heat and the susceptibility of systems up to size
16^3, we determine the Curie temperature of the 3D one-orbital double-exchange
model, which agrees with experimental values.Comment: 11 pages, 9 figures, RevTex4, additional references cite
Genomewide Association Scan of Suicidal Thoughts and Behaviour in Major Depression
Background
Suicidal behaviour can be conceptualised as a continuum from suicidal ideation, to suicidal attempts to completed suicide. In this study we identify genes contributing to suicidal behaviour in the depression study RADIANT.
Methodology/Principal Findings
A quantitative suicidality score was composed of two items from the SCAN interview. In addition, the 251 depression cases with a history of serious suicide attempts were classified to form a discrete trait. The quantitative trait was correlated with younger onset of depression and number of episodes of depression, but not with gender. A genome-wide association study of 2,023 depression cases was performed to identify genes that may contribute to suicidal behaviour. Two Munich depression studies were used as replication cohorts to test the most strongly associated SNPs. No SNP was associated at genome-wide significance level. For the quantitative trait, evidence of association was detected at GFRA1, a receptor for the neurotrophin GDRA (p = 2e-06). For the discrete trait of suicide attempt, SNPs in KIAA1244 and RGS18 attained p-values of <5e-6. None of these SNPs showed evidence for replication in the additional cohorts tested. Candidate gene analysis provided some support for a polymorphism in NTRK2, which was previously associated with suicidality.
Conclusions/Significance
This study provides a genome-wide assessment of possible genetic contribution to suicidal behaviour in depression but indicates a genetic architecture of multiple genes with small effects. Large cohorts will be required to dissect this further
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