226 research outputs found
A Note on Encodings of Phylogenetic Networks of Bounded Level
Driven by the need for better models that allow one to shed light into the
question how life's diversity has evolved, phylogenetic networks have now
joined phylogenetic trees in the center of phylogenetics research. Like
phylogenetic trees, such networks canonically induce collections of
phylogenetic trees, clusters, and triplets, respectively. Thus it is not
surprising that many network approaches aim to reconstruct a phylogenetic
network from such collections. Related to the well-studied perfect phylogeny
problem, the following question is of fundamental importance in this context:
When does one of the above collections encode (i.e. uniquely describe) the
network that induces it? In this note, we present a complete answer to this
question for the special case of a level-1 (phylogenetic) network by
characterizing those level-1 networks for which an encoding in terms of one (or
equivalently all) of the above collections exists. Given that this type of
network forms the first layer of the rich hierarchy of level-k networks, k a
non-negative integer, it is natural to wonder whether our arguments could be
extended to members of that hierarchy for higher values for k. By giving
examples, we show that this is not the case
Resonance as the Mechanism of Daytime Periodic Breathing in Patients with Heart Failure
Rationale: In patients with chronic heart failure, daytime oscillatory breathing at rest is associated with a high risk of mortality. Experimental evidence, including exaggerated ventilatory responses to CO2 and prolonged circulation time, implicates the ventilatory control system and suggests feedback instability (loop gain > 1) is responsible. However, daytime oscillatory patterns often appear remarkably irregular versus classic instability (Cheyne-Stokes respiration), suggesting our mechanistic understanding is limited.
Objectives: We propose that daytime ventilatory oscillations generally result from a chemoreflex resonance, in which spontaneous biological variations in ventilatory drive repeatedly induce temporary and irregular ringing effects. Importantly, the ease with which spontaneous biological variations induce irregular oscillations (resonance “strength”) rises profoundly as loop gain rises toward 1. We tested this hypothesis through a comparison of mathematical predictions against actual measurements in patients with heart failure and healthy control subjects.
Methods: In 25 patients with chronic heart failure and 25 control subjects, we examined spontaneous oscillations in ventilation and separately quantified loop gain using dynamic inspired CO2 stimulation.
Measurements and Main Results: Resonance was detected in 24 of 25 patients with heart failure and 18 of 25 control subjects. With increased loop gain—consequent to increased chemosensitivity and delay—the strength of spontaneous oscillations increased precipitously as predicted (r = 0.88), yielding larger (r = 0.78) and more regular (interpeak interval SD, r = −0.68) oscillations (P < 0.001 for all, both groups combined).
Conclusions: Our study elucidates the mechanism underlying daytime ventilatory oscillations in heart failure and provides a means to measure and interpret these oscillations to reveal the underlying chemoreflex hypersensitivity and reduced stability that foretells mortality in this population
Towards the reconstruction of integrated genome-scale models of metabolism and gene expression
The reconstruction of integrated genome-scale models of metabolism and gene expression has been a challenge for a while now. In fact, various methods that allow integrating reconstructions of Transcriptional Regulatory Networks, gene expression data or both into Genome-Scale Metabolic Models have been proposed. Several of these methods are surveyed in this article, which allowed identifying their strengths and weaknesses concerning the reconstruction of integrated models for multiple prokaryotic organisms. Additionally, the main resources of regulatory information were also surveyed, as the existence of novel sources of regulatory information and gene expression data may contribute for the improvement of methodologies referred herein.This study was supported by the Portuguese Foundation for Science andTechnology (FCT) under the scope of the strategic funding of UID/BIO/04469/2019 unit andBioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European RegionalDevelopment Fund under the scope of Norte2020-Programa Operacional Regional do Norte. Fernando Cruz holds a doctoral fellowship (SFRH/BD/139198/2018) funded by the FCT. The authors thank project SHIKIFACTORY100 - Modular cell factories for the production of 100 compounds from the shikimate pathway (814408) funded by the European Commission.info:eu-repo/semantics/publishedVersio
The quest for the solar g modes
Solar gravity modes (or g modes) -- oscillations of the solar interior for
which buoyancy acts as the restoring force -- have the potential to provide
unprecedented inference on the structure and dynamics of the solar core,
inference that is not possible with the well observed acoustic modes (or p
modes). The high amplitude of the g-mode eigenfunctions in the core and the
evanesence of the modes in the convection zone make the modes particularly
sensitive to the physical and dynamical conditions in the core. Owing to the
existence of the convection zone, the g modes have very low amplitudes at
photospheric levels, which makes the modes extremely hard to detect. In this
paper, we review the current state of play regarding attempts to detect g
modes. We review the theory of g modes, including theoretical estimation of the
g-mode frequencies, amplitudes and damping rates. Then we go on to discuss the
techniques that have been used to try to detect g modes. We review results in
the literature, and finish by looking to the future, and the potential advances
that can be made -- from both data and data-analysis perspectives -- to give
unambiguous detections of individual g modes. The review ends by concluding
that, at the time of writing, there is indeed a consensus amongst the authors
that there is currently no undisputed detection of solar g modes.Comment: 71 pages, 18 figures, accepted by Astronomy and Astrophysics Revie
Clusters of galaxies : observational properties of the diffuse radio emission
Clusters of galaxies, as the largest virialized systems in the Universe, are
ideal laboratories to study the formation and evolution of cosmic
structures...(abridged)... Most of the detailed knowledge of galaxy clusters
has been obtained in recent years from the study of ICM through X-ray
Astronomy. At the same time, radio observations have proved that the ICM is
mixed with non-thermal components, i.e. highly relativistic particles and
large-scale magnetic fields, detected through their synchrotron emission. The
knowledge of the properties of these non-thermal ICM components has increased
significantly, owing to sensitive radio images and to the development of
theoretical models. Diffuse synchrotron radio emission in the central and
peripheral cluster regions has been found in many clusters. Moreover
large-scale magnetic fields appear to be present in all galaxy clusters, as
derived from Rotation Measure (RM) studies. Non-thermal components are linked
to the cluster X-ray properties, and to the cluster evolutionary stage, and are
crucial for a comprehensive physical description of the intracluster medium.
They play an important role in the cluster formation and evolution. We review
here the observational properties of diffuse non-thermal sources detected in
galaxy clusters: halos, relics and mini-halos. We discuss their classification
and properties. We report published results up to date and obtain and discuss
statistical properties. We present the properties of large-scale magnetic
fields in clusters and in even larger structures: filaments connecting galaxy
clusters. We summarize the current models of the origin of these cluster
components, and outline the improvements that are expected in this area from
future developments thanks to the new generation of radio telescopes.Comment: Accepted for the publication in The Astronomy and Astrophysics
Review. 58 pages, 26 figure
Polyhydroxy Fullerenes (Fullerols or Fullerenols): Beneficial Effects on Growth and Lifespan in Diverse Biological Models
Recent toxicological studies on carbon nanomaterials, including fullerenes, have led to concerns about their safety. Functionalized fullerenes, such as polyhydroxy fullerenes (PHF, fullerols, or fullerenols), have attracted particular attention due to their water solubility and toxicity. Here, we report surprisingly beneficial and/or specific effects of PHF on model organisms representing four kingdoms, including the green algae Pseudokirchneriella subcapitata, the plant Arabidopsis thaliana, the fungus Aspergillus niger, and the invertebrate Ceriodaphnia dubia. The results showed that PHF had no acute or chronic negative effects on the freshwater organisms. Conversely, PHF could surprisingly increase the algal culture density over controls at higher concentrations (i.e., 72% increase by 1 and 5 mg/L of PHF) and extend the lifespan and stimulate the reproduction of Daphnia (e.g. about 38% by 20 mg/L of PHF). We also show that at certain PHF concentrations fungal growth can be enhanced and Arabidopsis thaliana seedlings exhibit longer hypocotyls, while other complex physiological processes remain unaffected. These findings may open new research fields in the potential applications of PHF, e.g., in biofuel production and aquaculture. These results will form the basis of further research into the mechanisms of growth stimulation and life extension by PHF
Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy
Background
A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets.
Methods
Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis.
Results
A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001).
Conclusion
We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty
Rapidity and Centrality Dependence of Proton and Anti-proton Production from Au+Au Collisions at sqrt(sNN) = 130GeV
We report on the rapidity and centrality dependence of proton and anti-proton
transverse mass distributions from Au+Au collisions at sqrt(sNN) = 130GeV as
measured by the STAR experiment at RHIC. Our results are from the rapidity and
transverse momentum range of |y|<0.5 and 0.35 <p_t<1.00GeV/c. For both protons
and anti-protons, transverse mass distributions become more convex from
peripheral to central collisions demonstrating characteristics of collective
expansion. The measured rapidity distributions and the mean transverse momenta
versus rapidity are flat within |y|<0.5. Comparisons of our data with results
from model calculations indicate that in order to obtain a consistent picture
of the proton(anti-proton) yields and transverse mass distributions the
possibility of pre-hadronic collective expansion may have to be taken into
account.Comment: 4 pages, 3 figures, 1 table, submitted to PR
EphA4 Blockers Promote Axonal Regeneration and Functional Recovery Following Spinal Cord Injury in Mice
Upregulation and activation of developmental axon guidance molecules, such as semaphorins and members of the Eph receptor tyrosine kinase family and their ligands, the ephrins, play a role in the inhibition of axonal regeneration following injury to the central nervous system. Previously we have demonstrated in a knockout model that axonal regeneration following spinal cord injury is promoted in the absence of the axon guidance protein EphA4. Antagonism of EphA4 was therefore proposed as a potential therapy to promote recovery from spinal cord injury. To further assess this potential, two soluble recombinant blockers of EphA4, unclustered ephrin-A5-Fc and EphA4-Fc, were examined for their ability to promote axonal regeneration and to improve functional outcome following spinal cord hemisection in wildtype mice. A 2-week administration of either of these blockers following spinal cord injury was sufficient to promote substantial axonal regeneration and functional recovery by 5 weeks following injury. Both inhibitors produced a moderate reduction in astrocytic gliosis, indicating that much of the effect of the blockers may be due to promotion of axon growth. These studies provide definitive evidence that soluble inhibitors of EphA4 function offer considerable therapeutic potential for the treatment of spinal cord injury and may have broader potential for the treatment of other central nervous system injuries
Identification of pediatric septic shock subclasses based on genome-wide expression profiling
<p>Abstract</p> <p>Background</p> <p>Septic shock is a heterogeneous syndrome within which probably exist several biological subclasses. Discovery and identification of septic shock subclasses could provide the foundation for the design of more specifically targeted therapies. Herein we tested the hypothesis that pediatric septic shock subclasses can be discovered through genome-wide expression profiling.</p> <p>Methods</p> <p>Genome-wide expression profiling was conducted using whole blood-derived RNA from 98 children with septic shock, followed by a series of bioinformatic approaches targeted at subclass discovery and characterization.</p> <p>Results</p> <p>Three putative subclasses (subclasses A, B, and C) were initially identified based on an empiric, discovery-oriented expression filter and unsupervised hierarchical clustering. Statistical comparison of the three putative subclasses (analysis of variance, Bonferonni correction, <it>P </it>< 0.05) identified 6,934 differentially regulated genes. K-means clustering of these 6,934 genes generated 10 coordinately regulated gene clusters corresponding to multiple signaling and metabolic pathways, all of which were differentially regulated across the three subclasses. Leave one out cross-validation procedures indentified 100 genes having the strongest predictive values for subclass identification. Forty-four of these 100 genes corresponded to signaling pathways relevant to the adaptive immune system and glucocorticoid receptor signaling, the majority of which were repressed in subclass A patients. Subclass A patients were also characterized by repression of genes corresponding to zinc-related biology. Phenotypic analyses revealed that subclass A patients were younger, had a higher illness severity, and a higher mortality rate than patients in subclasses B and C.</p> <p>Conclusion</p> <p>Genome-wide expression profiling can identify pediatric septic shock subclasses having clinically relevant phenotypes.</p
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