230 research outputs found
Fluctuation-stabilized marginal networks and anomalous entropic elasticity
We study the elastic properties of thermal networks of Hookean springs. In
the purely mechanical limit, such systems are known to have vanishing rigidity
when their connectivity falls below a critical, isostatic value. In this work
we show that thermal networks exhibit a non-zero shear modulus well below
the isostatic point, and that this modulus exhibits an anomalous, sublinear
dependence on temperature . At the isostatic point, increases as the
square-root of , while we find below the isostatic
point, where . We show that this anomalous dependence
is entropic in origin.Comment: 9 pages, 7 figure
Mild therapeutic hypothermia shortens intensive care unit stay of survivors after out-of-hospital cardiac arrest compared to historical controls
Therapeutic hypothermia after cardiac arrest – the implementation of the ILCOR guidelines in clinical routine is possible!
Impaired Lysosome Reformation in Chloroquine-Treated Retinal Pigment Epithelial Cells
PURPOSE: To model the in vivo effects of chloroquine on the retinal pigment epithelium in experimentally tractable cell culture systems and determine the effects of mild chloroquine treatment on lysosome function and turnover. METHODS: Effects of low-dose chloroquine treatment on lysosomal function and accessibility to newly endocytosed cargo were investigated in primary and embryonic stem cell-derived RPE cells and ARPE19 cells using fluorescence and electron microscopy of fluorescent and gold-labeled probes. Lysosomal protein expression and accumulation were measured by quantitative PCR and Western blotting. RESULTS: Initial chloroquine-induced lysosome neutralization was followed by partial recovery, lysosomal expansion, and accumulation of undegraded endocytic, phagocytic, and autophagic cargo and inhibition of cathepsin D processing. Accumulation of enlarged lysosomes was accompanied by a gradual loss of accessibility of these structures to the endocytic pathway, implying impaired lysosome reformation. Chloroquine-induced accumulation of pro-cathepsin D, as well as the lysosomal membrane protein, LAMP1, was reproduced by treatment with protease inhibitors and preceded changes in lysosomal gene expression. CONCLUSIONS: Low-dose chloroquine treatment inhibits lysosome reformation, causing a gradual depletion of lysosomes able to interact with cargo-carrying vacuoles and degrade their content. The resulting accumulation of newly synthesized pro-cathepsin D and LAMP1 reflects inhibition of normal turnover of lysosomal constituents and possibly lysosomes themselves. A better understanding of the mechanisms underlying lysosome reformation may reveal new targets for the treatment of chloroquine-induced retinopathy
Comparison of arterial plasma amino acid concentrations in rats fed ad lib oral chow or parenteral nutrition via intravenous or gastric infusion
Abstract from the 22nd Clinical Congress of the American Society for Parenteral and Enteral Nutrition, Orlando, FL, January 18-21, 1998
The REFOLD database: a tool for the optimization of protein expression and refolding
A large proportion of proteins expressed in Escherichia coli form inclusion bodies and thus require renaturation to attain a functional conformation for analysis. In this process, identifying and optimizing the refolding conditions and methodology is often rate limiting. In order to address this problem, we have developed REFOLD, a web-accessible relational database containing the published methods employed in the refolding of recombinant proteins. Currently, REFOLD contains >300 entries, which are heavily annotated such that the database can be searched via multiple parameters. We anticipate that REFOLD will continue to grow and eventually become a powerful tool for the optimization of protein renaturation. REFOLD is freely available at
Molecular motors robustly drive active gels to a critically connected state
Living systems often exhibit internal driving: active, molecular processes
drive nonequilibrium phenomena such as metabolism or migration. Active gels
constitute a fascinating class of internally driven matter, where molecular
motors exert localized stresses inside polymer networks. There is evidence that
network crosslinking is required to allow motors to induce macroscopic
contraction. Yet a quantitative understanding of how network connectivity
enables contraction is lacking. Here we show experimentally that myosin motors
contract crosslinked actin polymer networks to clusters with a scale-free size
distribution. This critical behavior occurs over an unexpectedly broad range of
crosslink concentrations. To understand this robustness, we develop a
quantitative model of contractile networks that takes into account network
restructuring: motors reduce connectivity by forcing crosslinks to unbind.
Paradoxically, to coordinate global contractions, motor activity should be low.
Otherwise, motors drive initially well-connected networks to a critical state
where ruptures form across the entire network.Comment: Main text: 21 pages, 5 figures. Supplementary Information: 13 pages,
8 figure
BVRI Light Curves for 29 Type Ia Supernovae
BVRI light curves are presented for 27 Type Ia supernovae discovered during
the course of the Calan/Tololo Survey and for two other SNe Ia observed during
the same period. Estimates of the maximum light magnitudes in the B, V, and I
bands and the initial decline rate parameter m15(B) are also given.Comment: 17 pages, figures and tables are not included (contact first author
if needed), to appear in the Astronomical Journa
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Exome sequencing identifies BRAF mutations in papillary craniopharyngiomas
Expansion of the Human Phenotype Ontology (HPO) knowledge base and resources.
The Human Phenotype Ontology (HPO)-a standardized vocabulary of phenotypic abnormalities associated with 7000+ diseases-is used by thousands of researchers, clinicians, informaticians and electronic health record systems around the world. Its detailed descriptions of clinical abnormalities and computable disease definitions have made HPO the de facto standard for deep phenotyping in the field of rare disease. The HPO\u27s interoperability with other ontologies has enabled it to be used to improve diagnostic accuracy by incorporating model organism data. It also plays a key role in the popular Exomiser tool, which identifies potential disease-causing variants from whole-exome or whole-genome sequencing data. Since the HPO was first introduced in 2008, its users have become both more numerous and more diverse. To meet these emerging needs, the project has added new content, language translations, mappings and computational tooling, as well as integrations with external community data. The HPO continues to collaborate with clinical adopters to improve specific areas of the ontology and extend standardized disease descriptions. The newly redesigned HPO website (www.human-phenotype-ontology.org) simplifies browsing terms and exploring clinical features, diseases, and human genes
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