328 research outputs found
Information heat engine: converting information to energy by feedback control
In 1929, Leo Szilard invented a feedback protocol in which a hypothetical
intelligence called Maxwell's demon pumps heat from an isothermal environment
and transduces it to work. After an intense controversy that lasted over eighty
years; it was finally clarified that the demon's role does not contradict the
second law of thermodynamics, implying that we can convert information to free
energy in principle. Nevertheless, experimental demonstration of this
information-to-energy conversion has been elusive. Here, we demonstrate that a
nonequilibrium feedback manipulation of a Brownian particle based on
information about its location achieves a Szilard-type information-energy
conversion. Under real-time feedback control, the particle climbs up a
spiral-stairs-like potential exerted by an electric field and obtains free
energy larger than the amount of work performed on it. This enables us to
verify the generalized Jarzynski equality, or a new fundamental principle of
"information-heat engine" which converts information to energy by feedback
control.Comment: manuscript including 7 pages and 4 figures and supplementary material
including 6 pages and 8 figure
Thermal properties of a string bit model at large N
We study the finite temperature properties of a recently introduced string
bit model designed to capture some features of the emergent string in the
tensionless limit. The model consists of a pair of bosonic and fermionic bit
operators transforming in the adjoint representation of the color group SU(N).
Color confinement is not achieved as a dynamical effect, but instead is
enforced by an explicit singlet projection. At large N and finite temperature,
the model has a non trivial thermodynamics. In particular, there is a Hagedorn
type transition at a finite temperature where the string degrees of
freedom are liberated and the free energy gets a large contribution that plays the role of an order parameter. For , the low
temperature phase becomes unstable. In the new phase, the thermodynamically
favoured configurations are characterized by a non-trivial gapped density of
the SU(N) angles associated with the singlet projection. We present an accurate
algorithm for the determination of the density profile at . In
particular, we determine the gap endpoint at generic temperature and analytical
expansions valid near the Hagedorn transition as well as at high temperature.
The leading order corrections are characterized by non-trivial exponents that
are determined analytically and compared with explicit numerical calculations.Comment: 15 pages, 8 pdf figure
Resource Modelling: The Missing Piece of the HTA Jigsaw?
Within health technology assessment (HTA), cost-effectiveness analysis and budget impact analyses have been broadly accepted as important components of decision making. However, whilst they address efficiency and affordability, the issue of implementation and feasibility has been largely ignored. HTA commonly takes place within a deliberative framework that captures issues of implementation and feasibility in a qualitative manner. We argue that only through a formal quantitative assessment of resource constraints can these issues be fully addressed. This paper argues the need for resource modelling to be considered explicitly in HTA. First, economic evaluation and budget impact models are described along with their limitations in evaluating feasibility. Next, resource modelling is defined and its usefulness is described along with examples of resource modelling from the literature. Then, the important issues that need to be considered when undertaking resource modelling are described before setting out recommendations for the use of resource modelling in HTA
Sphingomyelin is associated with kidney disease in type 1 diabetes (The FinnDiane Study)
Diabetic kidney disease, diagnosed by urinary albumin excretion rate (AER), is a critical symptom of chronic vascular injury in diabetes, and is associated with dyslipidemia and increased mortality. We investigated serum lipids in 326 subjects with type 1 diabetes: 56% of patients had normal AER, 17% had microalbuminuria (20 â¤Â AER < 200 Οg/min or 30 â¤Â AER < 300 mg/24 h) and 26% had overt kidney disease (macroalbuminuria AER âĽÂ 200 Οg/min or AER âĽÂ 300 mg/24 h). Lipoprotein subclass lipids and low-molecular-weight metabolites were quantified from native serum, and individual lipid species from the lipid extract of the native sample, using a proton NMR metabonomics platform. Sphingomyelin (odds ratio 2.53, P < 10â7), large VLDL cholesterol (odds ratio 2.36, P < 10â10), total triglycerides (odds ratio 1.88, P < 10â6), omega-9 and saturated fatty acids (odds ratio 1.82, P < 10â5), glucose disposal rate (odds ratio 0.44, P < 10â9), large HDL cholesterol (odds ratio 0.39, P < 10â9) and glomerular filtration rate (odds ratio 0.19, P < 10â10) were associated with kidney disease. No associations were found for polyunsaturated fatty acids or phospholipids. Sphingomyelin was a significant regressor of urinary albumin (P < 0.0001) in multivariate analysis with kidney function, glycemic control, body mass, blood pressure, triglycerides and HDL cholesterol. Kidney injury, sphingolipids and excess fatty acids have been linked in animal modelsâour exploratory approach provides independent support for this relationship in human patients with diabetes
Intrinsically Disordered Proteins Display No Preference for Chaperone Binding In Vivo
Intrinsically disordered/unstructured proteins (IDPs) are extremely sensitive to proteolysis in vitro, but show no enhanced degradation rates in vivo. Their existence and functioning may be explained if IDPs are preferentially associated with chaperones in the cell, which may offer protection against degradation by proteases. To test this inference, we took pairwise interaction data from high-throughput interaction studies and analyzed to see if predicted disorder correlates with the tendency of chaperone binding by proteins. Our major finding is that disorder predicted by the IUPred algorithm actually shows negative correlation with chaperone binding in E. coli, S. cerevisiae, and metazoa species. Since predicted disorder positively correlates with the tendency of partner binding in the interactome, the difference between the disorder of chaperone-binding and non-binding proteins is even more pronounced if normalized to their overall tendency to be involved in pairwise proteinâprotein interactions. We argue that chaperone binding is primarily required for folding of globular proteins, as reflected in an increased preference for chaperones of proteins in which at least one Pfam domain exists. In terms of the functional consequences of chaperone binding of mostly disordered proteins, we suggest that its primary reason is not the assistance of folding, but promotion of assembly with partners. In support of this conclusion, we show that IDPs that bind chaperones also tend to bind other proteins
The Overlap of Small Molecule and Protein Binding Sites within Families of Protein Structures
Proteinâprotein interactions are challenging targets for modulation by small molecules. Here, we propose an approach that harnesses the increasing structural coverage of protein complexes to identify small molecules that may target protein interactions. Specifically, we identify ligand and protein binding sites that overlap upon alignment of homologous proteins. Of the 2,619 protein structure families observed to bind proteins, 1,028 also bind small molecules (250â1000 Da), and 197 exhibit a statistically significant (p<0.01) overlap between ligand and protein binding positions. These âbi-functional positionsâ, which bind both ligands and proteins, are particularly enriched in tyrosine and tryptophan residues, similar to âenergetic hotspotsâ described previously, and are significantly less conserved than mono-functional and solvent exposed positions. Homology transfer identifies ligands whose binding sites overlap at least 20% of the protein interface for 35% of domainâdomain and 45% of domainâpeptide mediated interactions. The analysis recovered known small-molecule modulators of protein interactions as well as predicted new interaction targets based on the sequence similarity of ligand binding sites. We illustrate the predictive utility of the method by suggesting structural mechanisms for the effects of sanglifehrin A on HIV virion production, bepridil on the cellular entry of anthrax edema factor, and fusicoccin on vertebrate developmental pathways. The results, available at http://pibase.janelia.org, represent a comprehensive collection of structurally characterized modulators of protein interactions, and suggest that homologous structures are a useful resource for the rational design of interaction modulators
Erythrocyte and Porcine Intestinal Glycosphingolipids Recognized by F4 Fimbriae of Enterotoxigenic Escherichia coli
Enterotoxigenic F4-fimbriated Escherichia coli is associated with diarrheal disease in neonatal and postweaning pigs. The F4 fimbriae mediate attachment of the bacteria to the pig intestinal epithelium, enabling an efficient delivery of diarrhea-inducing enterotoxins to the target epithelial cells. There are three variants of F4 fimbriae designated F4ab, F4ac and F4ad, respectively, having different antigenic and adhesive properties. In the present study, the binding of isolated F4ab, F4ac and F4ad fimbriae, and F4ab/ac/ad-fimbriated E. coli, to glycosphingolipids from erythrocytes and from porcine small intestinal epithelium was examined, in order to get a comprehensive view of the F4-binding glycosphingolipids involved in F4-mediated hemagglutination and adhesion to the epithelial cells of porcine intestine. Specific interactions between the F4ab, F4ac and F4ad fimbriae and both acid and non-acid glycosphingolipids were obtained, and after isolation of binding-active glycosphingolipids and characterization by mass spectrometry and proton NMR, distinct carbohydrate binding patterns were defined for each fimbrial subtype. Two novel glycosphingolipids were isolated from chicken erythrocytes, and characterized as GalNAcÎą3GalNAcĂ3GalĂ4GlcĂ1Cer and GalNAcÎą3GalNAcĂ3GalĂ4GlcNAcĂ3GalĂ4GlcĂ1Cer. These two compounds, and lactosylceramide (GalĂ4GlcĂ1Cer) with phytosphingosine and hydroxy fatty acid, were recognized by all three variants of F4 fimbriae. No binding of the F4ad fimbriae or F4ad-fimbriated E. coli to the porcine intestinal glycosphingolipids occurred. However, for F4ab and F4ac two distinct binding patterns were observed. The F4ac fimbriae and the F4ac-expressing E. coli selectively bound to galactosylceramide (GalĂ1Cer) with sphingosine and hydroxy 24:0 fatty acid, while the porcine intestinal glycosphingolipids recognized by F4ab fimbriae and the F4ab-fimbriated bacteria were characterized as galactosylceramide, sulfatide (SO3-3GalĂ1Cer), sulf-lactosylceramide (SO3-3GalĂ4GlcĂ1Cer), and globotriaosylceramide (GalÎą4GalĂ4GlcĂ1Cer) with phytosphingosine and hydroxy 24:0 fatty acid. Finally, the F4ad fimbriae and the F4ad-fimbriated E. coli, but not the F4ab or F4ac subtypes, bound to reference gangliotriaosylceramide (GalNAcĂ4GalĂ4GlcĂ1Cer), gangliotetraosylceramide (GalĂ3GalNAcĂ4GalĂ4GlcĂ1Cer), isoglobotriaosylceramide (GalÎą3GalĂ4GlcĂ1Cer), and neolactotetraosylceramide (GalĂ4GlcNAcĂ3GalĂ4GlcĂ1Cer)
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