45 research outputs found
Crack-Like Processes Governing the Onset of Frictional Slip
We perform real-time measurements of the net contact area between two blocks
of like material at the onset of frictional slip. We show that the process of
interface detachment, which immediately precedes the inception of frictional
sliding, is governed by three different types of detachment fronts. These
crack-like detachment fronts differ by both their propagation velocities and by
the amount of net contact surface reduction caused by their passage. The most
rapid fronts propagate at intersonic velocities but generate a negligible
reduction in contact area across the interface. Sub-Rayleigh fronts are
crack-like modes which propagate at velocities up to the Rayleigh wave speed,
VR, and give rise to an approximate 10% reduction in net contact area. The most
efficient contact area reduction (~20%) is precipitated by the passage of slow
detachment fronts. These fronts propagate at anomalously slow velocities, which
are over an order of magnitude lower than VR yet orders of magnitude higher
than other characteristic velocity scales such as either slip or loading
velocities. Slow fronts are generated, in conjunction with intersonic fronts,
by the sudden arrest of sub-Rayleigh fronts. No overall sliding of the
interface occurs until either of the slower two fronts traverses the entire
interface, and motion at the leading edge of the interface is initiated. Slip
at the trailing edge of the interface accompanies the motion of both the slow
and sub-Rayleigh fronts. We might expect these modes to be important in both
fault nucleation and earthquake dynamics.Comment: 19 page, 5 figures, to appear in International Journal of Fractur
Verification of the Crooks fluctuation theorem and recovery of RNA folding free energies
The description of nonequilibrium processes in nano-sized objects, where the
typical energies involved are a few times, is increasingly becoming central to
disciplines as diverse as condensed-matter physics, materials science, and
biophysics. Major recent developments towards a unified treatment of
arbitrarily large fluctuations in small systems are described by fluctuation
theorems that relate the probabilities of a system absorbing from or releasing
to the bath a given amount of energy in a nonequilibrium process. Here we
experimentally verify the Crooks Fluctuation Theorem (CFT) under weak and
strong nonequilibrium conditions by using optical tweezers to measure the
irreversible mechanical work during the unfolding and refolding of a small RNA
hairpin and an RNA three-helix junction. We also show that the CFT provides a
powerful way to obtain folding free energies in biomolecules by determining the
crossing between the unfolding and refolding irreversible work distributions.
The method makes it possible to obtain folding free energies in nonequilibrium
processes that dissipate up to of the average total work exerted, thereby
paving the way for reconstructing free energy landscapes along reaction
coordinates in nonequilibrium single-molecule experiments.Comment: PDF file, 19 pages. Supplementary information available online at
www.nature.co
From START to FINISH : the influence of osmotic stress on the cell cycle
Peer reviewedPublisher PD
Second law, entropy production, and reversibility in thermodynamics of information
We present a pedagogical review of the fundamental concepts in thermodynamics
of information, by focusing on the second law of thermodynamics and the entropy
production. Especially, we discuss the relationship among thermodynamic
reversibility, logical reversibility, and heat emission in the context of the
Landauer principle and clarify that these three concepts are fundamentally
distinct to each other. We also discuss thermodynamics of measurement and
feedback control by Maxwell's demon. We clarify that the demon and the second
law are indeed consistent in the measurement and the feedback processes
individually, by including the mutual information to the entropy production.Comment: 43 pages, 10 figures. As a chapter of: G. Snider et al. (eds.),
"Energy Limits in Computation: A Review of Landauer's Principle, Theory and
Experiments
Using default constraints of the spindle assembly checkpoint to estimate the associated chemical rates
<p/> <p>Background</p> <p>Default activation of the spindle assembly checkpoint provides severe constraints on the underlying biochemical activation rates: on one hand, the cell cannot divide before all chromosomes are aligned, but on the other hand, when they are ready, the separation is quite fast, lasting a few minutes. Our purpose is to use these opposed constraints to estimate the associated chemical rates.</p> <p>Results</p> <p>To analyze the above constraints, we develop a markovian model to describe the dynamics of Cdc20 molecules. We compute the probability for no APC/C activation before time t, the distribution of Cdc20 at equilibrium and the mean time to complete APC/C activation after all chromosomes are attached.</p> <p>Conclusions</p> <p>By studying Cdc20 inhibition and the activation time, we obtain a range for the main chemical reaction rates regulating the spindle assembly checkpoint and transition to anaphase.</p
Towards quantum thermodynamics in electronicΒ circuits
Electronic circuits operating at sub-kelvin temperatures are attractive candidates for studying classical and quantum thermodynamics: their temperature can be controlled and measured locally with exquisite precision, and they allow experiments with large statistical samples. The availability and rapid development of devices such as quantum dots, single-electron boxes and superconducting qubits only enhance their appeal. But although these systems provide fertile ground for studying heat transport, entropy production and work in the context of quantum mechanics, the field remains in its infancy experimentally. Here, we review some recent experiments on quantum heat transport, fluctuation relations and implementations of Maxwellβs demon, revealing the rich physics yet to be fully probed in these systems.Peer reviewe
Explaining oscillations and variability in the p53-Mdm2 system
<p>Abstract</p> <p>Background</p> <p>In individual living cells p53 has been found to be expressed in a series of discrete pulses after DNA damage. Its negative regulator Mdm2 also demonstrates oscillatory behaviour. Attempts have been made recently to explain this behaviour by mathematical models but these have not addressed explicit molecular mechanisms. We describe two stochastic mechanistic models of the p53/Mdm2 circuit and show that sustained oscillations result directly from the key biological features, without assuming complicated mathematical functions or requiring more than one feedback loop. Each model examines a different mechanism for providing a negative feedback loop which results in p53 activation after DNA damage. The first model (ARF model) looks at the mechanism of p14<sup>ARF </sup>which sequesters Mdm2 and leads to stabilisation of p53. The second model (ATM model) examines the mechanism of ATM activation which leads to phosphorylation of both p53 and Mdm2 and increased degradation of Mdm2, which again results in p53 stabilisation. The models can readily be modified as further information becomes available, and linked to other models of cellular ageing.</p> <p>Results</p> <p>The ARF model is robust to changes in its parameters and predicts undamped oscillations after DNA damage so long as the signal persists. It also predicts that if there is a gradual accumulation of DNA damage, such as may occur in ageing, oscillations break out once a threshold level of damage is acquired. The ATM model requires an additional step for p53 synthesis for sustained oscillations to develop. The ATM model shows much more variability in the oscillatory behaviour and this variability is observed over a wide range of parameter values. This may account for the large variability seen in the experimental data which so far has examined ARF negative cells.</p> <p>Conclusion</p> <p>The models predict more regular oscillations if ARF is present and suggest the need for further experiments in ARF positive cells to test these predictions. Our work illustrates the importance of systems biology approaches to understanding the complex role of p53 in both ageing and cancer.</p
Modeling the Basal Dynamics of P53 System
The tumor suppressor p53 has become one of most investigated genes. Once activated by stress, p53 leads to cellular responses such as cell cycle arrest and apoptosis.Most previous models have ignored the basal dynamics of p53 under nonstressed conditions. To explore the basal dynamics of p53, we constructed a stochastic delay model by incorporating two negative feedback loops. We found that protein distribution of p53 under nonstressed condition is highly skewed with a fraction of cells showing high p53 levels comparable to those observed under stressed conditions. Under nonstressed conditions, asynchronous and spontaneous p53 pulses are triggered by basal DNA double strand breaks produced during normal cell cycle progression. The first peaking times show a predominant G1 distribution while the second ones are more widely distributed. The spontaneous pulses are triggered by an excitable mechanism. Once initiated, the amplitude and duration of pulses remain unchanged. Furthermore, the spontaneous pulses are filtered by ataxia telangiectasia mutated protein mediated posttranslational modifications and do not result in substantial p21 transcription. If challenged by externally severe DNA damage, cells generate synchronous p53 pulses and induce significantly high levels of p21. The high expression of p21 can also be partially induced by lowering the deacetylation rate.Our results demonstrated that the dynamics of p53 under nonstressed conditions is initiated by an excitable mechanism and cells become fully responsive only when cells are confronted with severe damage. These findings advance our understanding of the mechanism of p53 pulses and unlock many opportunities to p53-based therapy
Transcriptional Regulation Is a Major Controller of Cell Cycle Transition Dynamics
DNA replication, mitosis and mitotic exit are critical transitions of the cell cycle which normally occur only once per cycle. A universal control mechanism was proposed for the regulation of mitotic entry in which Cdk helps its own activation through two positive feedback loops. Recent discoveries in various organisms showed the importance of positive feedbacks in other transitions as well. Here we investigate if a universal control system with transcriptional regulation(s) and post-translational positive feedback(s) can be proposed for the regulation of all cell cycle transitions. Through computational modeling, we analyze the transition dynamics in all possible combinations of transcriptional and post-translational regulations. We find that some combinations lead to βsloppyβ transitions, while others give very precise control. The periodic transcriptional regulation through the activator or the inhibitor leads to radically different dynamics. Experimental evidence shows that in cell cycle transitions of organisms investigated for cell cycle dependent periodic transcription, only the inhibitor OR the activator is under cyclic control and never both of them. Based on these observations, we propose two transcriptional control modes of cell cycle regulation that either STOP or let the cycle GO in case of a transcriptional failure. We discuss the biological relevance of such differences