Dynamics of polydisperse irreversible adsorption: a pharmacological example

Many drug delivery systems suffer from undesirable interactions with the host immune system. It has been experimentally established that covalent attachment (irreversible adsorption) of suitable macromolecules to the surface of the drug carrier can reduce such undesirable interactions. A fundamental understanding of the adsorption process is still lacking. In this paper, the classical random irreversible adsorption model is generalized to capture certain essential processes involved in pharmacological applications, allowing for macromolecules of different sizes, partial overlapping of the tails of macromolecules, and the influence of reactions with the solvent on the adsorption process. Working in one dimension, an integro-differential evolution equation for the adsorption process is derived, and the asymptotic behavior of the surface area covered and the number of molecules attached to the surface are studied. Finally, equation-free dynamic renormalization tools are applied to study the asymptotically self-similar behavior of the adsorption statistics

Redundant Gs-coupled serotonin receptors regulate amyloid-β metabolism in vivo

BACKGROUND: The aggregation of amyloid-β (Aβ) into insoluble plaques is a hallmark pathology of Alzheimer’s disease (AD). Previous work has shown increasing serotonin levels with selective serotonin re-uptake inhibitor (SSRI) compounds reduces Aβ in the brain interstitial fluid (ISF) in a mouse model of AD and in the cerebrospinal fluid of humans. We investigated which serotonin receptor (5-HTR) subtypes and downstream effectors were responsible for this reduction. RESULTS: Agonists of 5-HT(4)R, 5-HT(6)R, and 5-HT(7)R significantly reduced ISF Aβ, but agonists of other receptor subtypes did not. Additionally, inhibition of Protein Kinase A (PKA) blocked the effects of citalopram, an SSRI, on ISF Aβ levels. Serotonin signaling does not appear to change gene expression to reduce Aβ levels in acute timeframes, but likely acts within the cytoplasm to increase α-secretase enzymatic activity. Broad pharmacological inhibition of putative α-secretases increased ISF Aβ and blocked the effects of citalopram. CONCLUSIONS: In total, these studies map the major signaling components linking serotonin receptors to suppression of brain ISF Aβ. These results suggest the reduction in ISF Aβ is mediated by a select group of 5-HTRs and open future avenues for targeted therapy of AD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13024-016-0112-5) contains supplementary material, which is available to authorized users

Utility of Non-rule-based Visual Matching as a Strategy to Allow Novices to Achieve Skin Lesion Diagnosis

Non-analytical reasoning is thought to play a key role in dermatology diagnosis. Considering its potential importance, surprisingly little work has been done to research whether similar identification processes can be supported in non-experts. We describe here a prototype diagnostic support software, which we have used to examine the ability of medical students (at the beginning and end of a dermatology attachment) and lay volunteers, to diagnose 12 images of common skin lesions. Overall, the non-experts using the software had a diagnostic accuracy of 98% (923/936) compared with 33% for the control group (215/648) (Wilcoxon p < 0.0001). We have demonstrated, within the constraints of a simplified clinical model, that novices’ diagnostic scores are significantly increased by the use of a structured image database coupled with matching of index and referent images. The novices achieve this high degree of accuracy without any use of explicit definitions of likeness or rule-based strategies

Local and Global Distinguishability in Quantum Interferometry

A statistical distinguishability based on relative entropy characterises the fitness of quantum states for phase estimation. This criterion is employed in the context of a Mach-Zehnder interferometer and used to interpolate between two regimes, of local and global phase distinguishability. The scaling of distinguishability in these regimes with photon number is explored for various quantum states. It emerges that local distinguishability is dependent on a discrepancy between quantum and classical rotational energy. Our analysis demonstrates that the Heisenberg limit is the true upper limit for local phase sensitivity. Only the `NOON' states share this bound, but other states exhibit a better trade-off when comparing local and global phase regimes.Comment: 4 pages, in submission, minor revision

Associations of Mitochondrial Fatty Acid Oxidation with Body Fat in Premenopausal Women

Higher in vivo fatty acid (FA) oxidation rates have been reported in obese individuals compared to lean counterparts; however whether this reflects a shift in substrate-specific oxidative capacity at the level of the skeletal muscle mitochondria has not been examined. The purpose of this study was to test the hypothesis that in situ measures of skeletal muscle mitochondria FA oxidation would be positively associated with total body fat. Participants were 38 premenopausal women (BMI=26.5±4.3 kg/m2). Total and regional fat were assessed by dual-energy X-ray absorptiometry (DXA). Mitochondrial FA oxidation was assessed in permeabilized myofibers using high-resolution respirometry and a palmitoyl carnitine substrate. We found positive associations of total fat mass with State 3 (ADP-stimulated respiration) (r=0.379, p<0.05) and the respiratory control ratio (RCR, measure of mitochondrial coupling) (r=0.348, p<0.05). When participants were dichotomized by high or low body fat percent, participants with high total body fat displayed a higher RCR compared to those with low body fat (p<0.05). There were no associations between any measure of regional fat and mitochondrial FA oxidation independent of total fat mass. In conclusion, greater FA oxidation in obesity may reflect molecular processes that enhance FA oxidation capacity at the mitochondrial level

The Globular Cluster Population of NGC 7457: Clues to the Evolution of Field S0 Galaxies

In this paper we present the results of a wide-field imaging study of the globular cluster (GC) system of the field S0 galaxy NGC 7457. To derive the global properties of the GC system, we obtained deep BVR images with the WIYN 3.5 m telescope and Minimosaic Imager and studied the GC population of NGC 7457 to a projected radius of approximately 30 kpc. Our ground-based data were combined with archival and published Hubble Space Telescope data to probe the properties of the GC system close to the galaxy center and reduce contamination in the GC candidate sample from foreground stars and background galaxies. We performed surface photometry of NGC 7457 and compared the galaxy's surface brightness profile with the surface density profile of the GC system. The profiles have similar shapes in the inner 1 arcminute (3.9 kpc), but the GC system profile appears to flatten relative to the galaxy light at larger radii. The GC system of NGC 7457 is noticeably elliptical in our images; we measure an ellipticity of 0.66 +/- 0.14 for the GC distribution, which is consistent with our measured ellipticity of the galaxy light. We integrated the radial surface density profile of the GC system to derive a total number of GCs N_GC = 210 +/- 30. The GC specific frequency normalized by the galaxy luminosity and mass are S_N = 3.1 +/- 0.7 and T = 4.8 +/- 1.1, respectively. Comparing the derived GC system properties and other empirical data for NGC 7457 to S0 formation scenarios suggests that this field S0 galaxy may have formed in an unequal-mass merger.Comment: 40 pages, 10 figures, accepted for publication in The Astrophysical Journa