182 research outputs found
Encoding folding paths of RNA switches
RNA co-transcriptional folding has long been suspected to play an active role
in helping proper native folding of ribozymes and structured regulatory motifs
in mRNA untranslated regions. Yet, the underlying mechanisms and coding
requirements for efficient co-transcriptional folding remain unclear.
Traditional approaches have intrinsic limitations to dissect RNA folding paths,
as they rely on sequence mutations or circular permutations that typically
perturb both RNA folding paths and equilibrium structures. Here, we show that
exploiting sequence symmetries instead of mutations can circumvent this problem
by essentially decoupling folding paths from equilibrium structures of designed
RNA sequences. Using bistable RNA switches with symmetrical helices conserved
under sequence reversal, we demonstrate experimentally that native and
transiently formed helices can guide efficient co-transcriptional folding into
either long-lived structure of these RNA switches. Their folding path is
controlled by the order of helix nucleations and subsequent exchanges during
transcription, and may also be redirected by transient antisense interactions.
Hence, transient intra- and intermolecular base pair interactions can
effectively regulate the folding of nascent RNA molecules into different native
structures, provided limited coding requirements, as discussed from an
information theory perspective. This constitutive coupling between RNA
synthesis and RNA folding regulation may have enabled the early emergence of
autonomous RNA-based regulation networks.Comment: 9 pages, 6 figure
Biomimetic emulsions reveal the effect of homeostatic pressure on cell-cell adhesion
Cell-cell contacts in tissues are continuously subject to mechanical forces
due to homeostatic pressure and active cytoskeleton dynamics. While much is
known about the molecular pathways of adhesion, the role of mechanics is less
well understood. To isolate the role of pressure we present a dense packing of
functionalized emulsion droplets in which surface interactions are tuned to
mimic those of real cells. By visualizing the microstructure in 3D we find that
a threshold compression force is necessary to overcome electrostatic repulsion
and surface elasticity and establish protein-mediated adhesion. Varying the
droplet interaction potential maps out a phase diagram for adhesion as a
function of force and salt concentration. Remarkably, fitting the data with our
theoretical model predicts binder concentrations in the adhesion areas that are
similar to those found in real cells. Moreover, we quantify the adhesion size
dependence on the applied force and thus reveal adhesion strengthening with
increasing homeostatic pressure even in the absence of active cellular
processes. This biomimetic approach reveals the physical origin of
pressure-sensitive adhesion and its strength across cell-cell junctions.Comment: 20 pages, 5 figure
A lattice Boltzmann model with random dynamical constraints
In this paper we introduce a modified lattice Boltzmann model (LBM) with the
capability of mimicking a fluid system with dynamic heterogeneities. The
physical system is modeled as a one-dimensional fluid, interacting with
finite-lifetime moving obstacles. Fluid motion is described by a lattice
Boltzmann equation and obstacles are randomly distributed semi-permeable
barriers which constrain the motion of the fluid particles. After a lifetime
delay, obstacles move to new random positions. It is found that the
non-linearly coupled dynamics of the fluid and obstacles produces heterogeneous
patterns in fluid density and non-exponential relaxation of two-time
autocorrelation function.Comment: 10 pages, 9 figures, to be published in Eur. Phys. J.
Tensorial Constitutive Models for Disordered Foams, Dense Emulsions, and other Soft Nonergodic Materials
In recent years, the paradigm of `soft glassy matter' has been used to
describe diverse nonergodic materials exhibiting strong local disorder and slow
mesoscopic rearrangement. As so far formulated, however, the resulting `soft
glassy rheology' (SGR) model treats the shear stress in isolation, effectively
`scalarizing' the stress and strain rate tensors. Here we offer generalizations
of the SGR model that combine its nontrivial aging and yield properties with a
tensorial structure that can be specifically adapted, for example, to the
description of fluid film assemblies or disordered foams.Comment: 18 pages, 4 figure
Localized Joule heating produced by ion current focusing through micron-size holes
We provide an experimental demonstration that the focusing of ionic currents
in a micron size hole connecting two chambers can produce local temperature
increases of up to C with gradients as large as K. We find a good agreement between the measured temperature profiles and
a finite elements-based numerical calculation. We show how the thermal
gradients can be used to measure the full melting profile of DNA duplexes
within a region of 40 m. The possibility to produce even larger gradients
using sub-micron pores is discussed.Comment: 3 pages, accepted to Appl. Phys. Lett
Rejuvenation and overaging in a colloidal glass under shear
We report the modifications of the microscopic dynamics of a colloidal glass
submitted to shear. We use multispeckle diffusing wave spectroscopy to monitor
the evolution of the spontaneous slow relaxation processes after the sample
have been submitted to various straining. We show that high shear rejuvenates
the system and accelerates its dynamics whereas moderate shear overage the
system. We analyze this phenomena within the frame of the Bouchaud's trap
model.Comment: 4 pages, 4 figures, to be published in PR
Generalizable Denoising of Microscopy Images using Generative Adversarial Networks and Contrastive Learning
Microscopy images often suffer from high levels of noise, which can hinder
further analysis and interpretation. Content-aware image restoration (CARE)
methods have been proposed to address this issue, but they often require large
amounts of training data and suffer from over-fitting. To overcome these
challenges, we propose a novel framework for few-shot microscopy image
denoising. Our approach combines a generative adversarial network (GAN) trained
via contrastive learning (CL) with two structure preserving loss terms
(Structural Similarity Index and Total Variation loss) to further improve the
quality of the denoised images using little data. We demonstrate the
effectiveness of our method on three well-known microscopy imaging datasets,
and show that we can drastically reduce the amount of training data while
retaining the quality of the denoising, thus alleviating the burden of
acquiring paired data and enabling few-shot learning. The proposed framework
can be easily extended to other image restoration tasks and has the potential
to significantly advance the field of microscopy image analysis
Multispeckle diffusing-wave spectroscopy: a tool to study slow relaxation and time-dependent dynamics
A multispeckle technique for efficiently measuring correctly
ensemble-averaged intensity autocorrelation functions of scattered light from
non-ergodic and/or non-stationary systems is described.
The method employs a CCD camera as a multispeckle light detector and a
computer-based correlator, and permits the simultaneous calculation of up to
500 correlation functions, where each correlation function is started at a
different time.
The correlation functions are calculated in real time and are referenced to a
unique starting time.
The multispeckle nature of the CCD camera detector means that a true ensemble
average is calculated; no time averaging is necessary.
The technique thus provides a "snapshot" of the dynamics, making it
particularly useful for non-stationary systems where the dynamics are changing
with time.
Delay times spanning the range from 1 ms to 1000 s are readily achieved with
this method.
The technique is demonstrated in the multiple scattering limit where
diffusing-wave spectroscopy theory applies.
The technique can also be combined with a recently-developed two-cell
technique that can measure faster decay times.
The combined technique can measure delay times from 10 ns to 1000 s.
The method is peculiarly well suited for studying aging processes in soft
glassy materials, which exhibit both short and long relaxation times,
non-ergodic dynamics, and slowly-evolving transient behavior.Comment: 11 pages 13 figures Accepted in Review of Scientific Instrument (june
02
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