292 research outputs found
Gaussian excitations model for glass-former dynamics and thermodynamics
We describe a model for the thermodynamics and dynamics of glass-forming
liquids in terms of excitations from an ideal glass state to a Gaussian
manifold of configurationally excited states. The quantitative fit of this
three parameter model to the experimental data on excess entropy and heat
capacity shows that ``fragile'' behavior, indicated by a sharply rising excess
heat capacity as the glass transition is approached from above, occurs in
anticipation of a first-order transition -- usually hidden below the glass
transition -- to a ``strong'' liquid state of low excess entropy. The dynamic
model relates relaxation to a hierarchical sequence of excitation events each
involving the probability of accumulating sufficient kinetic energy on a
separate excitable unit. Super-Arrhenius behavior of the relaxation rates, and
the known correlation of kinetic with thermodynamic fragility, both follow from
the way the rugged landscape induces fluctuations in the partitioning of energy
between vibrational and configurational manifolds. A relation is derived in
which the configurational heat capacity, rather than the configurational
entropy of the Adam Gibbs equation, controls the temperature dependence of the
relaxation times, and this gives a comparable account of the experimental
observations.Comment: 21 pp., 17 fig
Adaptive walks on time-dependent fitness landscapes
The idea of adaptive walks on fitness landscapes as a means of studying
evolutionary processes on large time scales is extended to fitness landscapes
that are slowly changing over time. The influence of ruggedness and of the
amount of static fitness contributions are investigated for model landscapes
derived from Kauffman's landscapes. Depending on the amount of static
fitness contributions in the landscape, the evolutionary dynamics can be
divided into a percolating and a non-percolating phase. In the percolating
phase, the walker performs a random walk over the regions of the landscape with
high fitness.Comment: 7 pages, 6 eps-figures, RevTeX, submitted to Phys. Rev.
Defining genes: a computational framework
The precise elucidation of the gene concept has become the subject of intense discussion in light of results from several, large high-throughput surveys of transcriptomes and proteomes. In previous work, we proposed an approach for constructing gene concepts that combines genomic heritability with elements of function. Here, we introduce a definition of the gene within a computational framework of cellular interactions. The definition seeks to satisfy the practical requirements imposed by annotation, capture logical aspects of regulation, and encompass the evolutionary property of homology
A sensitivity study of the neutral-neutral reactions C + C3 and C + C5 in cold dense interstellar clouds
Chemical networks used for models of interstellar clouds contain many
reactions, some of them with poorly determined rate coefficients and/or
products. In this work, we report a method for improving the predictions of
molecular abundances using sensitivity methods and ab initio calculations.
Based on the chemical network osu.2003, we used two different sensitivity
methods to determine the most important reactions as a function of time for
models of dense cold clouds. Of these reactions, we concentrated on those
between C and C3 and between C and C5, both for their effect on specific
important species such as CO and for their general effect on large numbers of
species. We then used ab initio and kinetic methods to determine an improved
rate coefficient for the former reaction and a new set of products, plus a
slightly changed rate coefficient for the latter. Putting our new results in a
pseudo-time-dependent model of cold dense clouds, we found that the abundances
of many species are altered at early times, based on large changes in the
abundances of CO and atomic C. We compared the effect of these new rate
coefficients/products on the comparison with observed abundances and found that
they shift the best agreement from 3e4 yr to (1-3)e5 yr
Microcanonical rates, gap times, and phase space dividing surfaces
The general approach to classical unimolecular reaction rates due to Thiele
is revisited in light of recent advances in the phase space formulation of
transition state theory for multidimensional systems. We analyze in detail the
gap time distribution and associated reactant lifetime distribution for the
isomerization reaction HCN CNH. Both algebraic (power law)
and exponential decay regimes have been identified. Statistical estimates of
the isomerization rate are compared with the numerically determined decay rate.
Examination of the decay properties of subsensembles of trajectories that exit
the HCN well through either of 2 available symmetry related product channels
shows that the complete trajectory ensemble effectively attains the full
symmetry of the system phase space on a short timescale ps,
after which the product branching ratio is 1:1, the "statistical" value. At
intermediate times, this statistical product ratio is accompanied by
nonexponential (nonstatistical) decay. We point out close parallels between the
dynamical behavior inferred from the gap time distribution for HCN and
nonstatistical behavior recently identified in reactions of some organic
molecules.Comment: 44 pages, 9 figure
First-line treatment and outcome of elderly patients with primary central nervous system lymphoma (PCNSL)âa systematic review and individual patient data meta-analysis
Evidence for prognosis and treatment of elderly patient with primary central nervous system is limited. High-dose methotrexate should be applied whenever possible, especially combination with oral alkylating agents is a promising approach. Further combinations with other intravenous drugs do not seem to improve outcome. More prospective trials designed for elderly PCNSL patients are warrante
Micro-pharmacokinetics: quantifying local drug concentration at live cell membranes
Fundamental equations for determining pharmacological parameters, such as the binding afnity of a ligand for its target receptor, assume a homogeneous distribution of ligand, with concentrations in the immediate vicinity of the receptor being the same as those in the bulk aqueous phase. It is, however, known that drugs are able to interact directly with the plasma membrane, potentially increasing local ligand concentrations around the receptor. We have previously reported an infuence of ligand-phospholipid interactions on ligand binding kinetics at the ÎČ2-adrenoceptor, which resulted in distinct âmicro-pharmacokineticâ ligand profles. Here, we directly quantifed the local concentration of BODIPY630/650-PEG8-S-propranolol (BY-propranolol), a fuorescent derivative of the classical ÎČ-blocker propranolol, at various distances above membranes of single living cells using fuorescence correlation spectroscopy. We show for the frst time a signifcantly increased ligand concentration immediatel adjacent to the cell membrane compared to the bulk aqueous phase. We further show a clear role of both the cell membrane and the ÎČ2-adrenoceptor in determining high local BY-propranolol concentrations at the cell surface. These data suggest that the true binding afnity of BY-propranolol for the ÎČ2-adrenoceptor is likely far lower than previously reported and highlights the critical importance of understanding the âmicro-pharmacokineticâ profles of ligands for membrane-associated proteins
Properties of metabolic graphs: biological organization or representation artifacts?
<p>Abstract</p> <p>Background</p> <p>Standard graphs, where each edge links two nodes, have been extensively used to represent the connectivity of metabolic networks. It is based on this representation that properties of metabolic networks, such as hierarchical and small-world structures, have been elucidated and null models have been proposed to derive biological organization hypotheses. However, these graphs provide a simplistic model of a metabolic network's connectivity map, since metabolic reactions often involve more than two reactants. In other words, this map is better represented as a hypergraph. Consequently, a question that naturally arises in this context is whether these properties truly reflect biological organization or are merely an artifact of the representation.</p> <p>Results</p> <p>In this paper, we address this question by reanalyzing topological properties of the metabolic network of <it>Escherichia coli </it>under a hypergraph representation, as well as standard graph abstractions. We find that when clustering is properly defined for hypergraphs and subsequently used to analyze metabolic networks, the scaling of clustering, and thus the hierarchical structure hypothesis in metabolic networks, become unsupported. Moreover, we find that incorporating the distribution of reaction sizes into the null model further weakens the support for the scaling patterns.</p> <p>Conclusions</p> <p>These results combined suggest that the reported scaling of the clustering coefficients in the metabolic graphs and its specific power coefficient may be an artifact of the graph representation, and may not be supported when biochemical reactions are atomically treated as hyperedges. This study highlights the implications of the way a biological system is represented and the null model employed on the elucidated properties, along with their support, of the system.</p
PAH chemistry and IR emission from circumstellar disks
Aims. The chemistry of, and infrared (IR) emission from, polycyclic aromatic
hydrocarbons (PAHs) in disks around Herbig Ae/Be and T Tauri stars are
investigated. The equilibrium distribution of the PAHs over all accessible
charge/hydrogenation states depends on the size and shape of the PAHs and on
the physical properties of the star and surrounding disk.
Methods. A chemistry model is created to calculate this equilibrium
distribution. Destruction of PAHs by ultraviolet (UV) photons, possibly in
multi-photon absorption events, is taken into account. The chemistry model is
coupled to a radiative transfer code to provide the physical parameters and to
combine the PAH emission with the spectral energy distribution (SED) from the
star+disk system.
Results. Normally hydrogenated PAHs in Herbig Ae/Be disks account for most of
the observed PAH emission, with neutral and positively ionized species
contributing in roughly equal amounts. Close to the midplane, the PAHs are more
strongly hydrogenated and negatively ionized, but these species do not
contribute to the overall emission because of the low UV/optical flux deep
inside the disk. PAHs of 50 carbon atoms are destroyed out to 100 AU in the
disk's surface layer, and the resulting spatial extent of the emission does not
agree well with observations. Rather, PAHs of about 100 carbon atoms or more
are predicted to cause most of the observed emission. The emission is extended
on a scale similar to that of the size of the disk. Furthermore, the emission
from T Tauri disks is much weaker and concentrated more towards the central
star than that from Herbig Ae/Be disks. Positively ionized PAHs are predicted
to be largely absent in T Tauri disks because of the weaker radiation field.Comment: 13 pages, 8 figures, accepted for publication in A&
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