412 research outputs found
Complete trails of co-authorship network evolution
The rise and fall of a research field is the cumulative outcome of its
intrinsic scientific value and social coordination among scientists. The
structure of the social component is quantifiable by the social network of
researchers linked via co-authorship relations, which can be tracked through
digital records. Here, we use such co-authorship data in theoretical physics
and study their complete evolutionary trail since inception, with a particular
emphasis on the early transient stages. We find that the co-authorship networks
evolve through three common major processes in time: the nucleation of small
isolated components, the formation of a tree-like giant component through
cluster aggregation, and the entanglement of the network by large-scale loops.
The giant component is constantly changing yet robust upon link degradations,
forming the network's dynamic core. The observed patterns are successfully
reproducible through a new network model
Flux networks in metabolic graphs
A metabolic model can be represented as bipartite graph comprising linked
reaction and metabolite nodes. Here it is shown how a network of conserved
fluxes can be assigned to the edges of such a graph by combining the reaction
fluxes with a conserved metabolite property such as molecular weight. A similar
flux network can be constructed by combining the primal and dual solutions to
the linear programming problem that typically arises in constraint-based
modelling. Such constructions may help with the visualisation of flux
distributions in complex metabolic networks. The analysis also explains the
strong correlation observed between metabolite shadow prices (the dual linear
programming variables) and conserved metabolite properties. The methods were
applied to recent metabolic models for Escherichia coli, Saccharomyces
cerevisiae, and Methanosarcina barkeri. Detailed results are reported for E.
coli; similar results were found for the other organisms.Comment: 9 pages, 4 figures, RevTeX 4.0, supplementary data available (excel
Machine learning applied to enzyme turnover numbers reveals protein structural correlates and improves metabolic models.
Knowing the catalytic turnover numbers of enzymes is essential for understanding the growth rate, proteome composition, and physiology of organisms, but experimental data on enzyme turnover numbers is sparse and noisy. Here, we demonstrate that machine learning can successfully predict catalytic turnover numbers in Escherichia coli based on integrated data on enzyme biochemistry, protein structure, and network context. We identify a diverse set of features that are consistently predictive for both in vivo and in vitro enzyme turnover rates, revealing novel protein structural correlates of catalytic turnover. We use our predictions to parameterize two mechanistic genome-scale modelling frameworks for proteome-limited metabolism, leading to significantly higher accuracy in the prediction of quantitative proteome data than previous approaches. The presented machine learning models thus provide a valuable tool for understanding metabolism and the proteome at the genome scale, and elucidate structural, biochemical, and network properties that underlie enzyme kinetics
Comparison of aneroid and oscillometric blood pressure measurements in children.
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This article is open access.Limited data exist on the comparison of blood pressure (BP) measurements using aneroid and oscillometric devices. The purpose of the study was to investigate the difference in BP obtained using oscillometric and aneroid BP monitors in 9- to 10-year-old children. A total of 979 children were divided into group O, which underwent two oscillometric BP readings followed by two aneroid readings, and group A, which had BP measured in the reverse order. No significant difference was found between the mean (±standard deviation) of the two systolic BP readings obtained using the oscillometric and aneroid devices (111.5±8.6 vs 111.3±8.1 mm Hg; P=.39), whereas the mean diastolic BP was lower with the oscillometric monitor (61.5±8.0 vs 64.5±6.8 mm Hg; P<.001). A significant downward trend in BP was observed with each consecutive measurement, and agreement between the two monitors was limited. Multiple BP measurements are, therefore, recommended before the diagnosis of elevated BP or hypertension is made with either method.Landspitali - The National University Hospital of Iceland Research Fun
Plasma 25-hydroxyvitamin D2 and D3 levels and incidence of postoperative atrial fibrillation.
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This article is open access.Low circulating levels of total 25-hydroxyvitamin D (25(OH)D) have been associated with an increased risk of adverse effects after cardiac surgery. The metabolites, 25(OH)D2 and 25(OH)D3, provide a good index of vitamin D status. In this study, we examined the association between preoperative plasma levels of total 25(OH)D, 25(OH)D2 and 25(OH)D3 and the risk of postoperative atrial fibrillation (POAF) following open heart surgery. The levels of plasma 25(OH)D2 and 25(OH)D3 in 118 patients, who underwent coronary artery bypass grafting and/or valvular surgery, were measured immediately prior to surgery and on postoperative day 3 by liquid chromatography-tandem mass spectrometry. Patients who developed POAF had higher median plasma levels of 25(OH)D2 than those who remained in sinus rhythm (SR) (P = 0·003), but no significant difference was noted in levels of 25(OH)D3 or total 25(OH)D between the two groups (P > 0·05). By univariate analysis, patients with total 25(OH)D and 25(OH)D2 levels above the median had higher frequency of POAF (P < 0·05) and the incidence of POAF increased significantly with each higher quartile of preoperative plasma levels of 25(OH)D2 (P = 0·001), an association that was independent of confounding factors. In both the SR and POAF groups, the median plasma levels of 25(OH)D2, 25(OH)D3 and total 25(OH)D were lower (P < 0·05) on the third postoperative day compared with preoperatively. Our findings demonstrate that higher plasma levels of 25(OH)D2 are associated with increased risk of POAF, while this is not the case for 25(OH)D3 or total 25(OH)D. The reason for these discrepant results is not clear but warrants further study
The solution space of metabolic networks: producibility, robustness and fluctuations
Flux analysis is a class of constraint-based approaches to the study of
biochemical reaction networks: they are based on determining the reaction flux
configurations compatible with given stoichiometric and thermodynamic
constraints. One of its main areas of application is the study of cellular
metabolic networks. We briefly and selectively review the main approaches to
this problem and then, building on recent work, we provide a characterization
of the productive capabilities of the metabolic network of the bacterium E.coli
in a specified growth medium in terms of the producible biochemical species.
While a robust and physiologically meaningful production profile clearly
emerges (including biomass components, biomass products, waste etc.), the
underlying constraints still allow for significant fluctuations even in key
metabolites like ATP and, as a consequence, apparently lay the ground for very
different growth scenarios.Comment: 10 pages, prepared for the Proceedings of the International Workshop
on Statistical-Mechanical Informatics, March 7-10, 2010, Kyoto, Japa
Quantifying the connectivity of a network: The network correlation function method
Networks are useful for describing systems of interacting objects, where the
nodes represent the objects and the edges represent the interactions between
them. The applications include chemical and metabolic systems, food webs as
well as social networks. Lately, it was found that many of these networks
display some common topological features, such as high clustering, small
average path length (small world networks) and a power-law degree distribution
(scale free networks). The topological features of a network are commonly
related to the network's functionality. However, the topology alone does not
account for the nature of the interactions in the network and their strength.
Here we introduce a method for evaluating the correlations between pairs of
nodes in the network. These correlations depend both on the topology and on the
functionality of the network. A network with high connectivity displays strong
correlations between its interacting nodes and thus features small-world
functionality. We quantify the correlations between all pairs of nodes in the
network, and express them as matrix elements in the correlation matrix. From
this information one can plot the correlation function for the network and to
extract the correlation length. The connectivity of a network is then defined
as the ratio between this correlation length and the average path length of the
network. Using this method we distinguish between a topological small world and
a functional small world, where the latter is characterized by long range
correlations and high connectivity. Clearly, networks which share the same
topology, may have different connectivities, based on the nature and strength
of their interactions. The method is demonstrated on metabolic networks, but
can be readily generalized to other types of networks.Comment: 10 figure
Development and pilot testing of an integrated, web-based self-management program for irritable bowel syndrome (IBS)
Although essential, many medical practices are unable to adequately support irritable bowel syndrome (IBS) patient self-management. Web-based programs can help overcome these barriers
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Genome-scale reconstructions of the mammalian secretory pathway predict metabolic costs and limitations of protein secretion
In mammalian cells, >25% of synthesized proteins are exported through the secretory pathway. The pathway complexity, however, obfuscates its impact on the secretion of different proteins. Unraveling its impact on diverse proteins is particularly important for biopharmaceutical production. Here we delineate the core secretory pathway functions and integrate them with genome-scale metabolic reconstructions of human, mouse, and Chinese hamster ovary\ua0cells. The resulting reconstructions enable the computation of energetic costs and machinery demands of each secreted protein. By integrating additional omics data, we find that highly secretory cells have adapted to reduce expression and secretion of other expensive host cell proteins. Furthermore, we predict metabolic costs and maximum productivities of biotherapeutic proteins and identify protein features that most significantly impact protein secretion. Finally, the model successfully predicts the increase in secretion of a monoclonal antibody after silencing a highly expressed selection marker. This work represents a knowledgebase of the mammalian secretory pathway that serves as a novel tool for systems biotechnology
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