1,264 research outputs found
Failure of the work-Hamiltonian connection for free energy calculations
Extensions of statistical mechanics are routinely being used to infer free
energies from the work performed over single-molecule nonequilibrium
trajectories. A key element of this approach is the ubiquitous expression
dW/dt=\partial H(x,t)/ \partial t which connects the microscopic work W
performed by a time-dependent force on the coordinate x with the corresponding
Hamiltonian H(x,t) at time t. Here we show that this connection, as pivotal as
it is, cannot be used to estimate free energy changes. We discuss the
implications of this result for single-molecule experiments and atomistic
molecular simulations and point out possible avenues to overcome these
limitations
Spatiotemporal stochastic resonance in the Swift-Hohenberg equation
We show the appearance of spatiotemporal stochastic resonance in the Swift-Hohenberg equation. This phenomenon emerges when a control parameter varies periodically in time around the bifurcation point. By using general scaling arguments and by taking into account the common features occurring in a bifurcation, we outline possible manifestations of the phenomenon in other pattern-forming systems
Determinants of population responses to environmental fluctuations
Environmental fluctuations, such as changing conditions and variable nutrient availability, are an unavoidable component of the dynamics of virtually all populations. They affect populations in ways that are often difficult to predict and sometimes lead to paradoxical outcomes. Here, we present a general analytical approach to examine how populations respond to fluctuations. We show that there exist general explicit conditions that determine to what extent fluctuations propagate to the variability of the responses and how they change the behavior of the system, including whether they promote proliferation or death and whether they facilitate coexistence or exclusion of competing species. These conditions depend on linear and nonlinear terms of the growth rate and on the characteristic times of the fluctuations. We validated our general approach through computational experiments for both stochastic and chaotic fluctuations and for multiple types of systems. From an applied point of view, our results provide an avenue for the precise control of the population behavior through fluctuations in addition to just through average properties
Noise suppression by noise
We have analyzed the interplay between an externally added noise and the
intrinsic noise of systems that relax fast towards a stationary state, and
found that increasing the intensity of the external noise can reduce the total
noise of the system. We have established a general criterion for the appearance
of this phenomenon and discussed two examples in detail.Comment: 4 pages, 4 figure
Optimal resting-growth strategies of microbial populations in fluctuating environments
Bacteria spend most of their lifetime in non-growing states which allow them to survive extended periods of stress and starvation. When environments improve, they must quickly resume growth to maximize their share of limited nutrients. Cells with higher stress resistance often survive longer stress durations at the cost of needing more time to resume growth, a strong disadvantage in competitive environments. Here we analyze the basis of optimal strategies that microorganisms can use to cope with this tradeoff. We explicitly show that the prototypical inverse relation between stress resistance and growth rate can explain much of the different types of behavior observed in stressed microbial populations. Using analytical mathematical methods, we determine the environmental parameters that decide whether cells should remain vegetative upon stress exposure, downregulate their metabolism to an intermediate optimum level, or become dormant. We find that cell-cell variability, or intercellular noise, is consistently beneficial in the presence of extreme environmental fluctuations, and that it provides an efficient population-level mechanism for adaption in a deteriorating environment. Our results reveal key novel aspects of responsive phenotype switching and its role as an adaptive strategy in changing environments
Far-from-equilibrium processes without net thermal exchange via energy sorting
Many important processes at the microscale require far-from-equilibrium
conditions to occur, as in the functioning of mesoscopic bioreactors,
nanoscopic rotors, and nanoscale mass conveyors. Achieving such conditions,
however, is typically based on energy inputs that strongly affect the thermal
properties of the environment and the controllability of the system itself.
Here, we present a general class of far-from-equilibrium processes that
suppress the net thermal exchange with the environment by maintaining the
Maxwell-Boltzmann velocity distribution intact. This new phenomenon, referred
to as ghost equilibrium, results from the statistical cancellation of
superheated and subcooled nonequilibrated degrees of freedom that are
autonomously generated through a microscale energy sorting process. We provide
general conditions to observe this phenomenon and study its implications for
manipulating energy at the microscale. The results are applied explicitly to
two mechanistically different cases, an ensemble of rotational dipoles and a
gas of trapped particles, which encompass a great variety of common situations
involving both rotational and translational degrees of freedom
Extracellular vesicles-based biomarkers represent a promising liquid biopsy in endometrial cancer
Tumor-derived extracellular vesicles (EVs) are secreted in large amounts into biological
fluids of cancer patients. The analysis of EVs cargoes has been associated with patient´s outcome
and response to therapy. However, current technologies for EVs isolation are tedious and low
cost-e cient for routine clinical implementation. To explore the clinical value of circulating EVs
analysis we attempted a proof-of-concept in endometrial cancer (EC) with ExoGAG, an easy to use
and highly e cient new technology to enrich EVs. Technical performance was first evaluated using
EVs secreted by Hec1A cells. Then, the clinical value of this strategy was questioned by analyzing the
levels of two well-known tissue biomarkers in EC, L1 cell adhesion molecule (L1CAM) and Annexin
A2 (ANXA2), in EVs purified from plasma in a cohort of 41 EC patients and 20 healthy controls.
The results demonstrated the specific content of ANXA2 in the purified EVs fraction, with an accurate
sensitivity and specificity for EC diagnosis. Importantly, high ANXA2 levels in circulating EVs
were associated with high risk of recurrence and non-endometrioid histology suggesting a potential
value as a prognostic biomarker in EC. These results also confirmed ExoGAG technology as a robust technique for the clinical implementation of circulating EVs analysesThis research was funded by Instituto de Salud Carlos III, grant PI17/01919, co-financed by the European
Regional Development Fund (FEDER), and by Fundación CientÃfica de la Asociación Española Contra el Cáncer
(AECC), Grupos ClÃnicos Coordinados 2018. Carolina Herrero is supported by a predoctoral i-PFIS fellowship
from Instituto de Salud Carlos III (IFI17/00047); Laura Muinelo is supported by Asociación Española Contra el Cáncer (AECC)
From cheek swabs to consensus sequences : an A to Z protocol for high-throughput DNA sequencing of complete human mitochondrial genomes
Background: Next-generation DNA sequencing (NGS) technologies have made huge impacts in many fields of biological research, but especially in evolutionary biology. One area where NGS has shown potential is for high-throughput sequencing of complete mtDNA genomes (of humans and other animals). Despite the increasing use of NGS technologies and a better appreciation of their importance in answering biological questions, there remain significant obstacles to the successful implementation of NGS-based projects, especially for new users.
Results: Here we present an ‘A to Z’ protocol for obtaining complete human mitochondrial (mtDNA) genomes – from DNA extraction to consensus sequence. Although designed for use on humans, this protocol could also be used to sequence small, organellar genomes from other species, and also nuclear loci. This protocol includes DNA extraction, PCR amplification, fragmentation of PCR products, barcoding of fragments, sequencing using the 454 GS FLX platform, and a complete bioinformatics pipeline (primer removal, reference-based mapping, output of coverage plots and SNP calling).
Conclusions: All steps in this protocol are designed to be straightforward to implement, especially for researchers who are undertaking next-generation sequencing for the first time. The molecular steps are scalable to large numbers (hundreds) of individuals and all steps post-DNA extraction can be carried out in 96-well plate format. Also, the protocol has been assembled so that individual ‘modules’ can be swapped out to suit available resources
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