160 research outputs found
Non-Markovian polymer reaction kinetics
Describing the kinetics of polymer reactions, such as the formation of loops
and hairpins in nucleic acids or polypeptides, is complicated by the structural
dynamics of their chains. Although both intramolecular reactions, such as
cyclization, and intermolecular reactions have been studied extensively, both
experimentally and theoretically, there is to date no exact explicit analytical
treatment of transport-limited polymer reaction kinetics, even in the case of
the simplest (Rouse) model of monomers connected by linear springs. We
introduce a new analytical approach to calculate the mean reaction time of
polymer reactions that encompasses the non-Markovian dynamics of monomer
motion. This requires that the conformational statistics of the polymer at the
very instant of reaction be determined, which provides, as a by-product, new
information on the reaction path. We show that the typical reactive
conformation of the polymer is more extended than the equilibrium conformation,
which leads to reaction times significantly shorter than predicted by the
existing classical Markovian theory.Comment: Main text (7 pages, 5 figures) + Supplemantary Information (13 pages,
2 figures
Event-related alpha suppression in response to facial motion
This article has been made available through the Brunel Open Access Publishing Fund.While biological motion refers to both face and body movements, little is known about the visual perception of facial motion. We therefore examined alpha wave suppression as a reduction in power is thought to reflect visual activity, in addition to attentional reorienting and memory processes. Nineteen neurologically healthy adults were tested on their ability to discriminate between successive facial motion captures. These animations exhibited both rigid and non-rigid facial motion, as well as speech expressions. The structural and surface appearance of these facial animations did not differ, thus participants decisions were based solely on differences in facial movements. Upright, orientation-inverted and luminance-inverted facial stimuli were compared. At occipital and parieto-occipital regions, upright facial motion evoked a transient increase in alpha which was then followed by a significant reduction. This finding is discussed in terms of neural efficiency, gating mechanisms and neural synchronization. Moreover, there was no difference in the amount of alpha suppression evoked by each facial stimulus at occipital regions, suggesting early visual processing remains unaffected by manipulation paradigms. However, upright facial motion evoked greater suppression at parieto-occipital sites, and did so in the shortest latency. Increased activity within this region may reflect higher attentional reorienting to natural facial motion but also involvement of areas associated with the visual control of body effectors. © 2014 Girges et al
Numerical approximations for the tempered fractional Laplacian: Error analysis and applications
In this paper, we propose an accurate finite difference method to discretize
the -dimensional (for ) tempered integral fractional Laplacian and
apply it to study the tempered effects on the solution of problems arising in
various applications. Compared to other existing methods, our method has higher
accuracy and simpler implementation. Our numerical method has an accuracy of
, for if (or if ) with
, suggesting the minimum consistency conditions. The accuracy can
be improved to , for if
(or if ). Numerical experiments confirm our analytical results and provide
insights in solving the tempered fractional Poisson problem. It suggests that
to achieve the second order of accuracy, our method only requires the solution
for any . Moreover, if the solution
of tempered fractional Poisson problems satisfies for and , our method has the accuracy
of . Since our method yields a (multilevel) Toeplitz stiffness
matrix, one can design fast algorithms via the fast Fourier transform for
efficient simulations. Finally, we apply it together with fast algorithms to
study the tempered effects on the solutions of various tempered fractional
PDEs, including the Allen-Cahn equation and Gray-Scott equations.Comment: 21 pages, 11 figures, 3 table
Acoustic Oddball during NREM Sleep: A Combined EEG/fMRI Study
Background: A condition vital for the consolidation and maintenance of sleep is generally reduced responsiveness to external stimuli. Despite this, the sleeper maintains a level of stimulus processing that allows to respond to potentially dangerous environmental signals. The mechanisms that subserve these contradictory functions are only incompletely understood. Methodology/Principal Findings: Using combined EEG/fMRI we investigated the neural substrate of sleep protection by applying an acoustic oddball paradigm during light NREM sleep. Further, we studied the role of evoked K-complexes (KCs), an electroencephalographic hallmark of NREM sleep with a still unknown role for sleep protection. Our main results were: (1) Other than in wakefulness, rare tones did not induce a blood oxygenation level dependent (BOLD) signal increase in the auditory pathway but a strong negative BOLD response in motor areas and the amygdala. (2) Stratification of rare tones by the presence of evoked KCs detected activation of the auditory cortex, hippocampus, superior and middle frontal gyri and posterior cingulate only for rare tones followed by a KC. (3) The typical high frontocentral EEG deflections of KCs were not paralleled by a BOLD equivalent. Conclusions/Significance: We observed that rare tones lead to transient disengagement of motor and amygdala responses during light NREM sleep. We interpret this as a sleep protective mechanism to delimit motor responses and to reduce the sensitivity of the amygdala towards further incoming stimuli. Evoked KCs are suggested to originate from a brain state wit
Fractional dynamics pharmacokinetics–pharmacodynamic models
While an increasing number of fractional order integrals and differential equations applications have been reported in the physics, signal processing, engineering and bioengineering literatures, little attention has been paid to this class of models in the pharmacokinetics–pharmacodynamic (PKPD) literature. One of the reasons is computational: while the analytical solution of fractional differential equations is available in special cases, it this turns out that even the simplest PKPD models that can be constructed using fractional calculus do not allow an analytical solution. In this paper, we first introduce new families of PKPD models incorporating fractional order integrals and differential equations, and, second, exemplify and investigate their qualitative behavior. The families represent extensions of frequently used PK link and PD direct and indirect action models, using the tools of fractional calculus. In addition the PD models can be a function of a variable, the active drug, which can smoothly transition from concentration to exposure, to hyper-exposure, according to a fractional integral transformation. To investigate the behavior of the models we propose, we implement numerical algorithms for fractional integration and for the numerical solution of a system of fractional differential equations. For simplicity, in our investigation we concentrate on the pharmacodynamic side of the models, assuming standard (integer order) pharmacokinetics
Regional adaptation defines sensitivity to future ocean acidification
Physiological responses to temperature are known to be a major determinant of species distributions and can dictate the sensitivity of populations to global warming. In contrast, little is known about how other major global change drivers, such as ocean acidification (OA), will
shape species distributions in the future. Here, by integrating population genetics with experimental data for growth and mineralization, physiology and metabolomics, we
demonstrate that the sensitivity of populations of the gastropod Littorina littorea to future OA is shaped by regional adaptation. Individuals from populations towards the edges of the natural latitudinal range in the Northeast Atlantic exhibit greater shell dissolution and the inability to upregulate their metabolism when exposed to low pH, thus appearing most sensitive to low seawater pH. Our results suggest that future levels of OA could mediate
temperature-driven shifts in species distributions, thereby influencing future biogeography and the functioning of marine ecosystems
Comment on Fractional Fokker–Planck Equation with Space and Time Dependent Drift and Diffusion
Fluidization and Resolidification of the Human Bladder Smooth Muscle Cell in Response to Transient Stretch
Background: Cells resident in certain hollow organs are subjected routinely to large transient stretches, including every adherent cell resident in lungs, heart, great vessels, gut, and bladder. We have shown recently that in response to a transient stretch the adherent eukaryotic cell promptly fluidizes and then gradually resolidifies, but mechanism is not yet understood. Principal Findings: In the isolated human bladder smooth muscle cell, here we applied a 10% transient stretch while measuring cell traction forces, elastic modulus, F-actin imaging and the F-actin/G-actin ratio. Immediately after a transient stretch, F-actin levels and cell stiffness were lower by about 50%, and traction forces were lower by about 70%, both indicative of prompt fluidization. Within 5min, F-actin levels recovered completely, cell stiffness recovered by about 90%, and traction forces recovered by about 60%, all indicative of resolidification. The extent of the fluidization response was uninfluenced by a variety of signaling inhibitors, and, surprisingly, was localized to the unstretch phase of the stretch-unstretch maneuver in a manner suggestive of cytoskeletal catch bonds. When we applied an “unstretch-restretch” (transient compression), rather than a “stretch-unstretch” (transient stretch), the cell did not fluidize and the actin network did not depolymerize. Conclusions: Taken together, these results implicate extremely rapid actin disassembly in the fluidization response, and slow actin reassembly in the resolidification response. In the bladder smooth muscle cell, the fluidization response to transient stretch occurs not through signaling pathways, but rather through release of increased tensile forces that drive acute disassociation of actin
The optical rebrightening of GRB100814A: an interplay of forward and reverse shocks?
We present a wide dataset of -ray, X-ray, UVOIR, and radio observations of the Swift GRB100814A. At the end of the slow decline phase of the X-ray and optical afterglow, this burst shows a sudden and prominent rebrightening in the optical band only, followed by a fast decay in both bands. The optical rebrightening also shows chromatic evolution. Such a puzzling behaviour cannot be explained by a single component model. We discuss other possible interpretations, and we find that a model that incorporates a long-lived reverse shock and forward shock fits the temporal and
spectral properties of GRB100814 the best
H2AX phosphorylation at the sites of DNA double-strand breaks in cultivated mammalian cells and tissues
A sequence variant of histone H2A called H2AX is one of the key components of chromatin involved in DNA damage response induced by different genotoxic stresses. Phosphorylated H2AX (γH2AX) is rapidly concentrated in chromatin domains around DNA double-strand breaks (DSBs) after the action of ionizing radiation or chemical agents and at stalled replication forks during replication stress. γH2AX foci could be easily detected in cell nuclei using immunofluorescence microscopy that allows to use γH2AX as a quantitative marker of DSBs in various applications. H2AX is phosphorylated in situ by ATM, ATR, and DNA-PK kinases that have distinct roles in different pathways of DSB repair. The γH2AX serves as a docking site for the accumulation of DNA repair proteins, and after rejoining of DSBs, it is released from chromatin. The molecular mechanism of γH2AX dephosphorylation is not clear. It is complicated and requires the activity of different proteins including phosphatases and chromatin-remodeling complexes. In this review, we summarize recently published data concerning the mechanisms and kinetics of γH2AX loss in normal cells and tissues as well as in those deficient in ATM, DNA-PK, and DSB repair proteins activity. The results of the latest scientific research of the low-dose irradiation phenomenon are presented including the bystander effect and the adaptive response estimated by γH2AX detection in cells and tissues
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