89 research outputs found
Nonequilibrium models of optimal enhancer function
In prokaryotes, thermodynamic models of gene regulation provide a highly quantitative mapping from promoter sequences to gene-expression levels that is compatible with in vivo and in vitro biophysical measurements. Such concordance has not been achieved for models of enhancer function in eukaryotes. In equilibrium models, it is difficult to reconcile the reported short transcription factor (TF) residence times on the DNA with the high specificity of regulation. In nonequilibrium models, progress is difficult due to an explosion in the number of parameters. Here, we navigate this complexity by looking for minimal nonequilibrium enhancer models that yield desired regulatory phenotypes: low TF residence time, high specificity, and tunable cooperativity. We find that a single extra parameter, interpretable as the âlinking rate,â by which bound TFs interact with Mediator components, enables our models to escape equilibrium bounds and access optimal regulatory phenotypes, while remaining consistent with the reported phenomenology and simple enough to be inferred from upcoming experiments. We further find that high specificity in nonequilibrium models is in a trade-off with gene-expression noise, predicting bursty dynamicsâan experimentally observed hallmark of eukaryotic transcription. By drastically reducing the vast parameter space of nonequilibrium enhancer models to a much smaller subspace that optimally realizes biological function, we deliver a rich class of models that could be tractably inferred from data in the near future
Common bursting relationships underlie eukaryotic transcription dynamics
Transcription commonly occurs in bursts resulting from alternating productive
(ON) and quiescent (OFF) periods. Yet how transcriptional bursts are regulated
to determine spatiotemporal transcriptional activity remains unclear. Here we
perform live transcription imaging of key developmental genes in the fly
embryo, with single polymerase sensitivity. Quantification of single allele
transcription rates and multi-polymerase bursts reveals shared bursting
relationships among all genes, across time and space, as well as cis- and
trans-perturbations. We identify the allele's ON-probability as the main
determinant of the transcription rate, while changes in the transcription
initiation rate are limited. Any given ON-probability determines a specific
combination of mean ON and OFF times, preserving a constant characteristic
bursting time scale. Our findings point to a convergence of various regulatory
processes that predominantly affect the ON-probability, thereby controlling
mRNA production rather than mechanism-specific modulation of ON and OFF times.
Our results thus motivate and guide new investigations into the mechanisms
implementing these bursting rules and governing transcriptional regulation
Quantum computation in optical lattices via global laser addressing
A scheme for globally addressing a quantum computer is presented along with
its realisation in an optical lattice setup of one, two or three dimensions.
The required resources are mainly those necessary for performing quantum
simulations of spin systems with optical lattices, circumventing the necessity
for single qubit addressing. We present the control procedures, in terms of
laser manipulations, required to realise universal quantum computation. Error
avoidance with the help of the quantum Zeno effect is presented and a scheme
for globally addressed error correction is given. The latter does not require
measurements during the computation, facilitating its experimental
implementation. As an illustrative example, the pulse sequence for the
factorisation of the number fifteen is given.Comment: 11 pages, 10 figures, REVTEX. Initialisation and measurement
procedures are adde
Structure of silent transcription intervals and noise characteristics of mammalian genes
Mammalian transcription occurs stochastically in short bursts interspersed by silent intervals showing a refractory period. However, the underlying processes and consequences on fluctuations in gene products are poorly understood. Here, we use single allele time-lapse recordings in mouse cells to identify minimal models of promoter cycles, which inform on the number and durations of rate-limiting steps responsible for refractory periods. The structure of promoter cycles is gene specific and independent of genomic location. Typically, five rate-limiting steps underlie the silent periods of endogenous promoters, while minimal synthetic promoters exhibit only one. Strikingly, endogenous or synthetic promoters with TATA boxes show simplified two-state promoter cycles. Since transcriptional bursting constrains intrinsic noise depending on the number of promoter steps, this explains why TATA box genes display increased intrinsic noise genome-wide in mammals, as revealed by single-cell RNA-seq. These findings have implications for basic transcription biology and shed light on interpreting single-cell RNA-counting experiments
Simulating open quantum systems: from many-body interactions to stabilizer pumping
In a recent experiment, Barreiro et al. demonstrated the fundamental building
blocks of an open-system quantum simulator with trapped ions [Nature 470, 486
(2011)]. Using up to five ions, single- and multi-qubit entangling gate
operations were combined with optical pumping in stroboscopic sequences. This
enabled the implementation of both coherent many-body dynamics as well as
dissipative processes by controlling the coupling of the system to an
artificial, suitably tailored environment. This engineering was illustrated by
the dissipative preparation of entangled two- and four-qubit states, the
simulation of coherent four-body spin interactions and the quantum
non-demolition measurement of a multi-qubit stabilizer operator. In the present
paper, we present the theoretical framework of this gate-based ("digital")
simulation approach for open-system dynamics with trapped ions. In addition, we
discuss how within this simulation approach minimal instances of spin models of
interest in the context of topological quantum computing and condensed matter
physics can be realized in state-of-the-art linear ion-trap quantum computing
architectures. We outline concrete simulation schemes for Kitaev's toric code
Hamiltonian and a recently suggested color code model. The presented simulation
protocols can be adapted to scalable and two-dimensional ion-trap
architectures, which are currently under development.Comment: 27 pages, 9 figures, submitted to NJP Focus on Topological Quantum
Computatio
Anyonic interferometry and protected memories in atomic spin lattices
Strongly correlated quantum systems can exhibit exotic behavior called
topological order which is characterized by non-local correlations that depend
on the system topology. Such systems can exhibit remarkable phenomena such as
quasi-particles with anyonic statistics and have been proposed as candidates
for naturally fault-tolerant quantum computation. Despite these remarkable
properties, anyons have never been observed in nature directly. Here we
describe how to unambiguously detect and characterize such states in recently
proposed spin lattice realizations using ultra-cold atoms or molecules trapped
in an optical lattice. We propose an experimentally feasible technique to
access non-local degrees of freedom by performing global operations on trapped
spins mediated by an optical cavity mode. We show how to reliably read and
write topologically protected quantum memory using an atomic or photonic qubit.
Furthermore, our technique can be used to probe statistics and dynamics of
anyonic excitations.Comment: 14 pages, 6 figure
A quantum spin transducer based on nano electro-mechancial resonator arrays
Implementation of quantum information processing faces the contradicting
requirements of combining excellent isolation to avoid decoherence with the
ability to control coherent interactions in a many-body quantum system. For
example, spin degrees of freedom of electrons and nuclei provide a good quantum
memory due to their weak magnetic interactions with the environment. However,
for the same reason it is difficult to achieve controlled entanglement of spins
over distances larger than tens of nanometers. Here we propose a universal
realization of a quantum data bus for electronic spin qubits where spins are
coupled to the motion of magnetized mechanical resonators via magnetic field
gradients. Provided that the mechanical system is charged, the magnetic moments
associated with spin qubits can be effectively amplified to enable a coherent
spin-spin coupling over long distances via Coulomb forces. Our approach is
applicable to a wide class of electronic spin qubits which can be localized
near the magnetized tips and can be used for the implementation of hybrid
quantum computing architectures
Can One Trust Quantum Simulators?
Various fundamental phenomena of strongly-correlated quantum systems such as
high- superconductivity, the fractional quantum-Hall effect, and quark
confinement are still awaiting a universally accepted explanation. The main
obstacle is the computational complexity of solving even the most simplified
theoretical models that are designed to capture the relevant quantum
correlations of the many-body system of interest. In his seminal 1982 paper
[Int. J. Theor. Phys. 21, 467], Richard Feynman suggested that such models
might be solved by "simulation" with a new type of computer whose constituent
parts are effectively governed by a desired quantum many-body dynamics.
Measurements on this engineered machine, now known as a "quantum simulator,"
would reveal some unknown or difficult to compute properties of a model of
interest. We argue that a useful quantum simulator must satisfy four
conditions: relevance, controllability, reliability, and efficiency. We review
the current state of the art of digital and analog quantum simulators. Whereas
so far the majority of the focus, both theoretically and experimentally, has
been on controllability of relevant models, we emphasize here the need for a
careful analysis of reliability and efficiency in the presence of
imperfections. We discuss how disorder and noise can impact these conditions,
and illustrate our concerns with novel numerical simulations of a paradigmatic
example: a disordered quantum spin chain governed by the Ising model in a
transverse magnetic field. We find that disorder can decrease the reliability
of an analog quantum simulator of this model, although large errors in local
observables are introduced only for strong levels of disorder. We conclude that
the answer to the question "Can we trust quantum simulators?" is... to some
extent.Comment: 20 pages. Minor changes with respect to version 2 (some additional
explanations, added references...
Parentsâ experiences of caring for a young person with neurofibromatosis type 1 (NF1): a qualitative study
Neurofibromatosis type 1 (NF1) is a variable and unpredictable genetic condition that can lead to changes to an individualâs appearance. Research has started to explore childrenâs and young peopleâs experiences of living with the condition; however, there is a lack of research with parents. This exploratory qualitative study set out to examine parentsâ experiences of caring for a young person with NF1. Seven parents took part in semi structured interviews which were subjected to a thematic analysis. Three key themes were identified which related to managing the uncertainty of the condition, the impact of an altered appearance, and othersâ awareness and understanding of NF1. Parents felt that understanding NF1 themselves in order to support their child was beneficial whilst a perceived lack of understanding by others was cited as a significant challenge. Parents require trustworthy information and also more widely call for greater understanding and awareness of the condition
- âŠ