201 research outputs found
A meta-analysis of Boolean network models reveals design principles of gene regulatory networks
Gene regulatory networks (GRNs) describe how a collection of genes governs
the processes within a cell. Understanding how GRNs manage to consistently
perform a particular function constitutes a key question in cell biology. GRNs
are frequently modeled as Boolean networks, which are intuitive, simple to
describe, and can yield qualitative results even when data is sparse.
We generate an expandable database of published, expert-curated Boolean GRN
models, and extracted the rules governing these networks. A meta-analysis of
this diverse set of models enables us to identify fundamental design principles
of GRNs.
The biological term canalization reflects a cell's ability to maintain a
stable phenotype despite ongoing environmental perturbations. Accordingly,
Boolean canalizing functions are functions where the output is already
determined if a specific variable takes on its canalizing input, regardless of
all other inputs. We provide a detailed analysis of the prevalence of
canalization and show that most rules describing the regulatory logic are
highly canalizing. Independent from this, we also find that most rules exhibit
a high level of redundancy. An analysis of the prevalence of small network
motifs, e.g. feed-forward loops or feedback loops, in the wiring diagram of the
identified models reveals several highly abundant types of motifs, as well as a
surprisingly high overabundance of negative regulations in complex feedback
loops. Lastly, we provide the strongest evidence thus far in favor of the
hypothesis that GRNs operate at the critical edge between order and chaos.Comment: 12 pages, 8 figure
Metataxonomic and Metagenomic Approaches vs. Culture-Based Techniques for Clinical Pathology.
Diagnoses that are both timely and accurate are critically important for patients with life-threatening or drug resistant infections. Technological improvements in High-Throughput Sequencing (HTS) have led to its use in pathogen detection and its application in clinical diagnoses of infectious diseases. The present study compares two HTS methods, 16S rRNA marker gene sequencing (metataxonomics) and whole metagenomic shotgun sequencing (metagenomics), in their respective abilities to match the same diagnosis as traditional culture methods (culture inference) for patients with ventilator associated pneumonia (VAP). The metagenomic analysis was able to produce the same diagnosis as culture methods at the species-level for five of the six samples, while the metataxonomic analysis was only able to produce results with the same species-level identification as culture for two of the six samples. These results indicate that metagenomic analyses have the accuracy needed for a clinical diagnostic tool, but full integration in diagnostic protocols is contingent on technological improvements to decrease turnaround time and lower costs
Bird sensitivity to disturbance as an indicator of forest patchconditions: An issue in environmental assessments
An Environmental Assessment (EA) is one of the steps within the Environmental Impact Assessment process. Birds are often used in EA to help decision makers evaluate potential human impacts from proposed development activities. A “sensitivity to human disturbance” index, created by Parker III et al. (1996) for all Neotropical species, is commonly considered an ecological indicator. However, this parameter was created subjectively and, for most species, there have been no rigorous field test to validate its effectiveness as such. Therefore, in this study, we aim to: (1) evaluate if, at the local scale, birds from forest patches in a human-modified landscape (HML) may differ in sensitivity from Parker's sensitivity classification; (2) evaluate the effectiveness of the species richness value at each sensitivity level as an ecological indicator; (3) gather information on how often and in which manner Parker's classification has been used in EA. To do so, bird sampling was performed in eight forest patches in a HML over one year. Then, we created a local sensitivity to disturbance using information about threat, endemism, spatial distribution and relative abundance of all species in the study area. We found that 37% of the forest birds showed different local sensitivity levels when compared with Parker's classification. Our results show that only the richness of high-sensitivity species from our local classification fitted the ecological indicator assumptions helping the environmental conditions evaluation of the studied patches. We conclude that species richness of each Parker's bird sensitivity levels do not necessarily perform as an ecological indicator at the local scale, and particularly in HML. Nevertheless, Parker's Neotropical bird sensitivity classification was used in 50% of EA we reviewed. In these, 76% assumed that it was an accurate ecological indicator of the local forest conditions for birds. The lack of clear criteria used in Parker's classification allows diverse interpretations by ornithologists, and there is no agreement about the ecological meaning of each sensitivity level and what environmental conditions each level may indicate of. Therefore, the use of Parker's classification in EA may jeopardize accurate interpretations of proposed anthropogenic impacts. Furthermore, because a bird species’ sensitivity often varies between locations, we argue that Parker's generalized classification of bird sensitivity should not be used as an indicator of forest environmental conditions in EA throughout HMLs in Neotropics. Rather, local bird ecological indices should be explored, otherwise, erroneous predictions of the anthropogenic impacts will continue to be common
LSST Science Book, Version 2.0
A survey that can cover the sky in optical bands over wide fields to faint
magnitudes with a fast cadence will enable many of the exciting science
opportunities of the next decade. The Large Synoptic Survey Telescope (LSST)
will have an effective aperture of 6.7 meters and an imaging camera with field
of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over
20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with
fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a
total point-source depth of r~27.5. The LSST Science Book describes the basic
parameters of the LSST hardware, software, and observing plans. The book
discusses educational and outreach opportunities, then goes on to describe a
broad range of science that LSST will revolutionize: mapping the inner and
outer Solar System, stellar populations in the Milky Way and nearby galaxies,
the structure of the Milky Way disk and halo and other objects in the Local
Volume, transient and variable objects both at low and high redshift, and the
properties of normal and active galaxies at low and high redshift. It then
turns to far-field cosmological topics, exploring properties of supernovae to
z~1, strong and weak lensing, the large-scale distribution of galaxies and
baryon oscillations, and how these different probes may be combined to
constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at
http://www.lsst.org/lsst/sciboo
Quiescence and γH2AX in neuroblastoma are regulated by ouabain/Na,K-ATPase
Cellular quiescence is a state of reversible proliferation arrest that is induced by anti-mitogenic signals. The endogenous cardiac glycoside ouabain is a specific ligand of the ubiquitous sodium pump, Na,K-ATPase, also known to regulate cell growth through unknown signalling pathways.
To investigate the role of ouabain/Na,K-ATPase in uncontrolled neuroblastoma growth we used xenografts, flow cytometry, immunostaining, comet assay, real-time PCR, and electrophysiology after various treatment strategies.
The ouabain/Na,K-ATPase complex induced quiescence in malignant neuroblastoma. Tumour growth was reduced by >50% when neuroblastoma cells were xenografted into immune-deficient mice that were fed with ouabain. Ouabain-induced S-G2 phase arrest, activated the DNA-damage response (DDR) pathway marker γH2AX, increased the cell cycle regulator p21Waf1/Cip1 and upregulated the quiescence-specific transcription factor hairy and enhancer of split1 (HES1), causing neuroblastoma cells to ultimately enter G0. Cells re-entered the cell cycle and resumed proliferation, without showing DNA damage, when ouabain was removed.
Conclusion:
These findings demonstrate a novel action of ouabain/Na,K-ATPase as a regulator of quiescence in neuroblastoma, suggesting that ouabain can be used in chemotherapies to suppress tumour growth and/or arrest cells to increase the therapeutic index in combination therapies
Psychological impact of lymphoma on adolescents and young adults: not a matter of black or white
Readout of a quantum processor with high dynamic range Josephson parametric amplifiers
We demonstrate a high dynamic range Josephson parametric amplifier (JPA) in
which the active nonlinear element is implemented using an array of rf-SQUIDs.
The device is matched to the 50 environment with a Klopfenstein-taper
impedance transformer and achieves a bandwidth of 250-300 MHz, with input
saturation powers up to -95 dBm at 20 dB gain. A 54-qubit Sycamore processor
was used to benchmark these devices, providing a calibration for readout power,
an estimate of amplifier added noise, and a platform for comparison against
standard impedance matched parametric amplifiers with a single dc-SQUID. We
find that the high power rf-SQUID array design has no adverse effect on system
noise, readout fidelity, or qubit dephasing, and we estimate an upper bound on
amplifier added noise at 1.6 times the quantum limit. Lastly, amplifiers with
this design show no degradation in readout fidelity due to gain compression,
which can occur in multi-tone multiplexed readout with traditional JPAs.Comment: 9 pages, 8 figure
Measurement-Induced State Transitions in a Superconducting Qubit: Within the Rotating Wave Approximation
Superconducting qubits typically use a dispersive readout scheme, where a
resonator is coupled to a qubit such that its frequency is qubit-state
dependent. Measurement is performed by driving the resonator, where the
transmitted resonator field yields information about the resonator frequency
and thus the qubit state. Ideally, we could use arbitrarily strong resonator
drives to achieve a target signal-to-noise ratio in the shortest possible time.
However, experiments have shown that when the average resonator photon number
exceeds a certain threshold, the qubit is excited out of its computational
subspace, which we refer to as a measurement-induced state transition. These
transitions degrade readout fidelity, and constitute leakage which precludes
further operation of the qubit in, for example, error correction. Here we study
these transitions using a transmon qubit by experimentally measuring their
dependence on qubit frequency, average photon number, and qubit state, in the
regime where the resonator frequency is lower than the qubit frequency. We
observe signatures of resonant transitions between levels in the coupled
qubit-resonator system that exhibit noisy behavior when measured repeatedly in
time. We provide a semi-classical model of these transitions based on the
rotating wave approximation and use it to predict the onset of state
transitions in our experiments. Our results suggest the transmon is excited to
levels near the top of its cosine potential following a state transition, where
the charge dispersion of higher transmon levels explains the observed noisy
behavior of state transitions. Moreover, occupation in these higher energy
levels poses a major challenge for fast qubit reset
Overcoming leakage in scalable quantum error correction
Leakage of quantum information out of computational states into higher energy
states represents a major challenge in the pursuit of quantum error correction
(QEC). In a QEC circuit, leakage builds over time and spreads through
multi-qubit interactions. This leads to correlated errors that degrade the
exponential suppression of logical error with scale, challenging the
feasibility of QEC as a path towards fault-tolerant quantum computation. Here,
we demonstrate the execution of a distance-3 surface code and distance-21
bit-flip code on a Sycamore quantum processor where leakage is removed from all
qubits in each cycle. This shortens the lifetime of leakage and curtails its
ability to spread and induce correlated errors. We report a ten-fold reduction
in steady-state leakage population on the data qubits encoding the logical
state and an average leakage population of less than
throughout the entire device. The leakage removal process itself efficiently
returns leakage population back to the computational basis, and adding it to a
code circuit prevents leakage from inducing correlated error across cycles,
restoring a fundamental assumption of QEC. With this demonstration that leakage
can be contained, we resolve a key challenge for practical QEC at scale.Comment: Main text: 7 pages, 5 figure
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