De-novo design of complementary (antisense) peptide mini-receptor inhibitor of interleukin 18 (IL-18).

Complementary (antisense) peptide mini-receptor inhibitors are complementary peptides designed to be receptor-surrogates that act by binding to selected surface features of biologically important proteins thereby inhibiting protein-cognate receptor interactions and subsequent biological effects. Previously, we described a complementary peptide mini-receptor inhibitor of interleukin-1beta (IL-1beta) that was designed to bind to an external surface loop (beta-bulge) of IL-1beta (Boraschi loop) clearly identified in the X-ray crystal structure of this cytokine. Here, we report the de-novo design and rational development of a complementary peptide mini-receptor inhibitor of cytokine interleukin-18 (IL-18), a protein for which there is no known X-ray crystal structure. Using sequence homology comparisons with IL-1beta, putative IL-18 surface loops are identified and used as a starting point for design, including a loop region 1 thought to be equivalent with the Boraschi loop of IL-1beta. Only loop region 1 complementary peptides are found to be promising leads as mini-receptor inhibitors of IL-18 but these are prevented from being properly successful owing to solubility problems. The application of "M-I pair mutagenesis" and inclusion of a C-terminal arginine residue are then sufficient to solve this problem and convert one lead peptide into a functional complementary peptide mini-receptor inhibitor of IL-18. This suggests that the biophysical and biological properties of complementary peptides can be improved in a rational and logical manner where appropriate, further strengthening the potential importance of complementary peptides as inhibitors of protein-protein interactions, even when X-ray crystal structural information is not readily available

Power-recycled weak-value-based metrology

We improve the precision of the interferometric weak-value-based beam deflection measurement by introducing a power recycling mirror, creating a resonant cavity. This results in \emph{all} the light exiting to the detector with a large deflection, thus eliminating the inefficiency of the rare postselection. The signal-to-noise ratio of the deflection is itself magnified by the weak value. We discuss ways to realize this proposal, using a transverse beam filter and different cavity designs.Comment: 5 pages, 1 figur

The long-term prognostic significance of 6-minute walk test distance in patients with chronic heart failure

Background. The 6-minute walk test (6-MWT) is used to assess patients with chronic heart failure (CHF). The prognostic significance of the 6-MWT distance during long-term followup ( > 5 years) is unclear. Methods. 1,667 patients (median [inter-quartile range, IQR]) (age 72 [65-77] ; 75% males) with heart failure due to left ventricular systolic impairment undertook a 6-MWT as part of their baseline assessment and were followed up for 5 years. Results. At 5 years' followup, those patients who died (n = 959) were older at baseline and had a higher log NT pro-BNP than those who survived to 5 years (n = 708). 6-MWT distance was lower in those who died [163 (153) m versus 269 (160) m; P 360 m. 6-MWT distance was a predictor of all-cause mortality (HR 0.97; 95% CI 0.96-0.97; Chi-square = 184.1; P < 0.0001). Independent predictors of all-cause mortality were decreasing 6-MWT distance, increasing age, increasing NYHA classification, increasing log NT pro-BNP, decreasing diastolic blood pressure, decreasing sodium, and increasing urea. Conclusion. The 6-MWT is an important independent predictor of all-cause mortality following long-term followup in patients with CHF. © 2014 Lee Ingle et al

Monitoring sediment transfer processes on the desert margin

LANDSAT Thematic Mapper and Multispectral Scanner data have been used to construct change detection images for three playas in south-central Tunisia. Change detection images have been used to analyze changes in surface reflectance and absorption between wet and dry season (intra-annual change) and between different years (inter-annual change). Change detection imagery has been used to examine geomorphological changes on the playas. Changes in geomorphological phenomena are interpreted from changes in soil and foliar moisture levels, differences in reflectances between different salt and sediments and the spatial expression of geomorphological features. Intra-annual change phenomena that can be detected from multidate imagery are changes in surface moisture, texture and chemical composition, vegetation cover and the extent of aeolian activity. Inter-annual change phenomena are divisible into those restricted to marginal playa facies (sedimentation from sheetwash and alluvial fans, erosion from surface runoff and cliff retreat) and these are found in central playa facies which are related to the internal redistribution of water, salt and sediment

Are Electrons Oscillating Photons, Oscillating “Vacuum," or Something Else? The 2015 Panel Discussion: An Unprecedented Engineering Opportunity: A Dynamical Linear Theory of Energy as Light and Matter

Platform: What physical attributes separate EM waves, of the enormous band of radio to visible to x-ray, from the high energy narrow band of gamma-ray? From radio to visible to x-ray, telescopes are designed based upon the optical imaging theory; which is an extension of the Huygens-Fresnel diffraction integral. Do we understand the physical properties of gamma rays that defy us to manipulate them similarly? One demonstrated unique property of gamma rays is that they can be converted to elementary particles (electron and positron pair); or a particle-antiparticle pair can be converted into gamma rays. Thus, EM waves and elementary particles, being inter-convertible; we cannot expect to understand the deeper nature of light without succeeding to find structural inter-relationship between photons and particles. This topic is directly relevant to develop a deeper understanding of the nature of light; which will, in turn, help our engineers to invent better optical instruments

High-Throughput Classification of Radiographs Using Deep Convolutional Neural Networks.

The study aimed to determine if computer vision techniques rooted in deep learning can use a small set of radiographs to perform clinically relevant image classification with high fidelity. One thousand eight hundred eighty-five chest radiographs on 909 patients obtained between January 2013 and July 2015 at our institution were retrieved and anonymized. The source images were manually annotated as frontal or lateral and randomly divided into training, validation, and test sets. Training and validation sets were augmented to over 150,000 images using standard image manipulations. We then pre-trained a series of deep convolutional networks based on the open-source GoogLeNet with various transformations of the open-source ImageNet (non-radiology) images. These trained networks were then fine-tuned using the original and augmented radiology images. The model with highest validation accuracy was applied to our institutional test set and a publicly available set. Accuracy was assessed by using the Youden Index to set a binary cutoff for frontal or lateral classification. This retrospective study was IRB approved prior to initiation. A network pre-trained on 1.2 million greyscale ImageNet images and fine-tuned on augmented radiographs was chosen. The binary classification method correctly classified 100 % (95 % CI 99.73-100 %) of both our test set and the publicly available images. Classification was rapid, at 38 images per second. A deep convolutional neural network created using non-radiological images, and an augmented set of radiographs is effective in highly accurate classification of chest radiograph view type and is a feasible, rapid method for high-throughput annotation

Epileptic high-frequency network activity in a model of non-lesional temporal lobe epilepsy

High-frequency cortical activity, particularly in the 250–600 Hz (fast ripple) band, has been implicated in playing a crucial role in epileptogenesis and seizure generation. Fast ripples are highly specific for the seizure initiation zone. However, evidence for the association of fast ripples with epileptic foci depends on animal models and human cases with substantial lesions in the form of hippocampal sclerosis, which suggests that neuronal loss may be required for fast ripples. In the present work, we tested whether cell loss is a necessary prerequisite for the generation of fast ripples, using a non-lesional model of temporal lobe epilepsy that lacks hippocampal sclerosis. The model is induced by unilateral intrahippocampal injection of tetanus toxin. Recordings from the hippocampi of freely-moving epileptic rats revealed high-frequency activity (4100 Hz), including fast ripples. High-frequency activity was present both during interictal discharges and seizure onset. Interictal fast ripples proved a significantly more reliable marker of the primary epileptogenic zone than the presence of either interictal discharges or ripples (100–250 Hz). These results suggest that fast ripple activity should be considered for its potential value in the pre-surgical workup of non-lesional temporal lobe epilepsy

CONCENTRATION ISSUES IN THE U.S. BEEF SUBSECTOR

Industrial Organization, Livestock Production/Industries,

NMR analysis of Nile Blue (C. I. Basic Blue 12) and Thionine (C. I. 52000) in solution

The dyes Nile Blue (C. I. Basic Blue 12, NB) and Thionine (C. I. 52000, TH) were examined in both ionic and neutral forms in different solvents using NMR and UV-visible Spectroscopy to firmly establish the structures of the molecules and to assess the nature and extent of their aggregating characteristics. 1H and 13C NMR assignments and chemical shift data were used along with (for NB) nuclear Overhauser effect information enabling a structure for self-assembly to be proposed. In both cases these data were supplemented with variable temperature, dilution and diffusion-based experimental results using 1H NMR spectroscopy thereby enabling the extended aggregate structures to be assessed in terms of the relative strength of self-association and the extent to which extended aggregates could form. Full and detailed solution phase NMR analysis of such dyes, especially the two studied in this context, have either not been widely reported or have not been studied to the depth presented here. The data and their interpretation form an important addition to the analysis of this class of dye compounds and provide additional insight into the effects of self-assembly on the behaviour of such molecules in various solution-phase environments