489 research outputs found
Quantum point contact due to Fermi-level pinning and doping profiles in semiconductor nanocolumns
We show that nanoscale doping profiles inside a nanocolumn in combination
with Fermi-level pinning at the surface give rise to the formation of a
saddle-point in the potential profile. Consequently, the lateral confinement
inside the channel varies along the transport direction, yielding an embedded
quantum point contact. An analytical estimation of the quantization energies
will be given
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Cellular resolution models for even skipped regulation in the entire Drosophila embryo
Transcriptional control ensures genes are expressed in the right amounts at the correct times and locations. Understanding quantitatively how regulatory systems convert input signals to appropriate outputs remains a challenge. For the first time, we successfully model even skipped (eve) stripes 2 and 3+7 across the entire fly embryo at cellular resolution. A straightforward statistical relationship explains how transcription factor (TF) concentrations define eve’s complex spatial expression, without the need for pairwise interactions or cross-regulatory dynamics. Simulating thousands of TF combinations, we recover known regulators and suggest new candidates. Finally, we accurately predict the intricate effects of perturbations including TF mutations and misexpression. Our approach imposes minimal assumptions about regulatory function; instead we infer underlying mechanisms from models that best fit the data, like the lack of TF-specific thresholds and the positional value of homotypic interactions. Our study provides a general and quantitative method for elucidating the regulation of diverse biological systems. DOI: http://dx.doi.org/10.7554/eLife.00522.00
Glauber dynamics in a single-chain magnet: From theory to real systems
The Glauber dynamics is studied in a single-chain magnet. As predicted, a
single relaxation mode of the magnetization is found. Above 2.7 K, the
thermally activated relaxation time is mainly governed by the effect of
magnetic correlations and the energy barrier experienced by each magnetic unit.
This result is in perfect agreement with independent thermodynamical
measurements. Below 2.7 K, a crossover towards a relaxation regime is observed
that is interpreted as the manifestation of finite-size effects. The
temperature dependences of the relaxation time and of the magnetic
susceptibility reveal the importance of the boundary conditions.Comment: Submitted to PRL 10 May 2003. Submitted to PRB 12 December 2003;
published 15 April 200
Machine learning models in electronic health records can outperform conventional survival models for predicting patient mortality in coronary artery disease
Prognostic modelling is important in clinical practice and epidemiology for patient management
and research. Electronic health records (EHR) provide large quantities of data for such
models, but conventional epidemiological approaches require significant researcher time to
implement. Expert selection of variables, fine-tuning of variable transformations and interactions,
and imputing missing values are time-consuming and could bias subsequent analysis,
particularly given that missingness in EHR is both high, and may carry meaning. Using a
cohort of 80,000 patients from the CALIBER programme, we compared traditional modelling
and machine-learning approaches in EHR. First, we used Cox models and random survival
forests with and without imputation on 27 expert-selected, preprocessed variables to
predict all-cause mortality. We then used Cox models, random forests and elastic net
regression on an extended dataset with 586 variables to build prognostic models and identify
novel prognostic factors without prior expert input. We observed that data-driven models
used on an extended dataset can outperform conventional models for prognosis, without
data preprocessing or imputing missing values. An elastic net Cox regression based with
586 unimputed variables with continuous values discretised achieved a C-index of 0.801
(bootstrapped 95% CI 0.799 to 0.802), compared to 0.793 (0.791 to 0.794) for a traditional
Cox model comprising 27 expert-selected variables with imputation for missing values. We
also found that data-driven models allow identification of novel prognostic variables; that the
absence of values for particular variables carries meaning, and can have significant implications
for prognosis; and that variables often have a nonlinear association with mortality,
which discretised Cox models and random forests can elucidate. This demonstrates that
machine-learning approaches applied to raw EHR data can be used to build models for use
in research and clinical practice, and identify novel predictive variables and their effects to
inform future research
Cytoplasmic cleavage of IMPA1 3' UTR is necessary for maintaining axon integrity
The 3′ untranslated regions (3′ UTRs) of messenger RNAs (mRNAs) are non-coding sequences involved in many aspects of mRNA metabolism, including intracellular localization and translation. Incorrect processing and delivery of mRNA cause severe developmental defects and have been implicated in many neurological disorders. Here, we use deep sequencing to show that in sympathetic neuron axons, the 3′ UTRs of many transcripts undergo cleavage, generating isoforms that express the coding sequence with a short 3′ UTR and stable 3′ UTR-derived fragments of unknown function. Cleavage of the long 3′ UTR of Inositol Monophosphatase 1 (IMPA1) mediated by a protein complex containing the endonuclease argonaute 2 (Ago2) generates a translatable isoform that is necessary for maintaining the integrity of sympathetic neuron axons. Thus, our study provides a mechanism of mRNA metabolism that simultaneously regulates local protein synthesis and generates an additional class of 3′ UTR-derived RNAs
Anomalous self-diffusion in the ferromagnetic Ising chain with Kawasaki dynamics
We investigate the motion of a tagged spin in a ferromagnetic Ising chain
evolving under Kawasaki dynamics. At equilibrium, the displacement is Gaussian,
with a variance growing as . The temperature dependence of the
prefactor is derived exactly. At low temperature, where the static
correlation length is large, the mean square displacement grows as
in the coarsening regime, i.e., as a finite fraction of the
mean square domain length. The case of totally asymmetric dynamics, where
(resp. ) spins move only to the right (resp. to the left), is also
considered. In the steady state, the displacement variance grows as . The temperature dependence of the prefactor is derived exactly,
using the Kardar-Parisi-Zhang theory. At low temperature, the displacement
variance grows as in the coarsening regime, again proportionally to
the mean square domain length.Comment: 22 pages, 8 figures. A few minor changes and update
Nyquist method for Wigner-Poisson quantum plasmas
By means of the Nyquist method, we investigate the linear stability of
electrostatic waves in homogeneous equilibria of quantum plasmas described by
the Wigner-Poisson system. We show that, unlike the classical Vlasov-Poisson
system, the Wigner-Poisson case does not necessarily possess a Penrose
functional determining its linear stability properties. The Nyquist method is
then applied to a two-stream distribution, for which we obtain an exact,
necessary and sufficient condition for linear stability, as well as to a
bump-in-tail equilibrium.Comment: 6 figure
Delocalization of states in two component superlattices with correlated disorder
Electron and phonon states in two different models of intentionally
disordered superlattices are studied analytically as well as numerically. The
localization length is calculated exactly and we found that it diverges for
particular energies or frequencies, suggesting the existence of delocalized
states for both electrons and phonons. Numerical calculations for the
transmission coefficient support the existence of these delocalized states.Comment: RevTeX, 12 pages, 2 PS figures adde
Patterns of subnet usage reveal distinct scales of regulation in the transcriptional regulatory network of Escherichia coli
The set of regulatory interactions between genes, mediated by transcription
factors, forms a species' transcriptional regulatory network (TRN). By
comparing this network with measured gene expression data one can identify
functional properties of the TRN and gain general insight into transcriptional
control. We define the subnet of a node as the subgraph consisting of all nodes
topologically downstream of the node, including itself. Using a large set of
microarray expression data of the bacterium Escherichia coli, we find that the
gene expression in different subnets exhibits a structured pattern in response
to environmental changes and genotypic mutation. Subnets with less changes in
their expression pattern have a higher fraction of feed-forward loop motifs and
a lower fraction of small RNA targets within them. Our study implies that the
TRN consists of several scales of regulatory organization: 1) subnets with more
varying gene expression controlled by both transcription factors and
post-transcriptional RNA regulation, and 2) subnets with less varying gene
expression having more feed-forward loops and less post-transcriptional RNA
regulation.Comment: 14 pages, 8 figures, to be published in PLoS Computational Biolog
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