A residual-free bubble formulation for nonlinear elliptic problems with oscillatory coefficients

We present an investigation of the Residual-Free Bubble (RFB) finite element method for a class of multiscale nonlinear elliptic partial differential equations. After proposing a nonlinear version for the method, we address fundamental questions as existence and uniqueness of solutions. We also obtain a best approximation result and investigate possible linearizations that generate different versions for the method. All estimates are independent of eventual oscillations in the coefficients, and as far as we are aware, this is the first time that an analysis for the nonlinear RFB method is considered.     

Binding and Enhanced Binding between Key Immunity Proteins TRAF6 and TIFA

Human tumor necrosis factor receptor associated factor (TRAF)-interacting protein, with a forkhead-associated domain (TIFA), is a key regulator of NF-κB activation. It also plays a key role in the activation of innate immunity in response to bacterial infection, through heptose 1,7-bisphosphate (HBP); a metabolite of lipopolysaccharide (LPS). However, the mechanism of TIFA function is largely unexplored, except for the suggestion of interaction with TRAF6. Herein, we provide evidence for direct binding, albeit weak, between TIFA and the TRAF domain of TRAF6, and it is shown that the binding is enhanced for a rationally designed double mutant, TIFA S174Q/M179D. Enhanced binding was also demonstrated for endogenous full-length TRAF6. Furthermore, the structures of the TRAF domain complexes with the consensus TRAF-binding peptides from the C terminus of wild-type and S174Q/M179D mutant TIFA, showing salt-bridge formation between residues 177–181 of TIFA and the binding pocket residues of the TRAF domain, were solved. Taken together, the results provide direct evidence and a structural basis for the TIFA–TRAF6 interaction, and show how this important biological function can be modulated.     

Design,Synthesis, and Characterization of Macrocyclic Inhibitors of the Proprotein Convertase Furin

The activation of viral glycoproteins by the host protease furin is an essential step in the replication of numerous pathogenic viruses. Thus, effective inhibitors of furin could serve as broad-spectrum antiviral drugs. A crystal structure of an inhibitory hexapeptide derivative in complex with furin served as template for the rational design of various types of new cyclic inhibitors. Most of the prepared derivatives are relatively potent furin inhibitors with inhibition constants in the low nanomolar or even sub-nanomolar range. For seven derivatives the crystal structures in complex with furin could be determined. In three complexes, electron density was found for the entire inhibitor. In the other cases the structures could be determined only for the P6/P5-P1 segments, which directly interact with furin. The cyclic derivatives together with two non-cyclic reference compounds were tested as inhibitors of the proteolytic activation and replication of respiratory syncytial virus in cells. Significant antiviral activity was found for both linear reference inhibitors, whereas a negligible efficacy was determined for the cyclic derivatives.     

Further investigation on the modified hyperbolic function in the CAM16 color appearance model

In the International Commission on Illumination (CIE) color appearance model CIECAM02, a modified hyperbolic function is used to represent luminance adaptation. The same nonlinear function is also used in the new color appearance model CAM16 [Color Res Appl., 2017;42:703‐718]. Although the modified hyperbolic function seems reasonable based on physiological evidence, it has an infinite slope at the origin, which causes instability for both the forward and inverse modes of the CIECAM02/CAM16 models. In this article, various possible extensions to the nonlinear luminance adaptation function in CIECAM02/CAM16 are reviewed and evaluated. Based on these investigations, the Gill extension to the hyperbolic function that is used to represent luminance adaptation [Proceedings of 16th Color and Imaging Conference, pp. 327‐331, 2008], is recommended at both the lower end (q < q_L ) and the upper end (q > q_U ), where q is the appropriate R_c , G_c , B_c (or R_wc , G_wc , B_wc ) response. In addition, the new recommended function can be readily inverted for use in the appropriate inverse appearance model. From an extensive analysis using available experimental data sets, we also propose that, for the lower and upper limits of the luminance range in the extended model, the values q_L = 0.26 and q_U = 150 be used, respectively.     

Color evolution during a coating process of pharmaceutical tablet cores by random spraying

Placebo white tablet cores (lactose anhydrous [47.6%], corn starch [23.8%], microcrystalline cellulose [19.1%], polyvinylpyrrolidone [7.9%], magnesium stearate [0.8%], and talcum powder [0.8%]) were coated with a colorant (hydroxypropyl methylcellulose [8% w/v], titanium dioxide [0.2% w/v], FD&C yellow No. 6 with aluminum lacquer [0.8% w/v], polyethylene glycol 4000 [0.4% w/v], and purified water [q.s.p. 100 mL]) using a random spraying method during 130 minutes. During the coating process, batches of 21 samples were extracted every 10 minutes and measured with a DigiEye imaging system. The initial cores showed very similar and uniform colors (Mean Color Difference from the Mean [MCDM] of 0.8 CIELAB units), but partially coated tablets showed lower uniformity (MCDM below 2.0 CIELAB units). There was a high color variability (MCDM about 4.0 CIELAB units) among tablets of the same batch in the period between 10 and 30 minutes, which decreased as the coating process progressed, until achieving a final acceptable value (MCDM below 2.0 CIELAB units). During the coating process, L^* decreased, C^*_ab strongly increased, and h _ab remained nearly constant (disregarding results at 0 and 10 minutes). CIELAB and CIEDE2000 color differences (mainly chroma differences) with respect to the initial color of the tablets were modeled as a function of time by exponential functions with three coefficients. The color change in the interval from 90 to 130 minutes (4.3 CIELAB units, or 2.6 CIEDE2000 units), may be considered negligible bearing in mind the color variability in the batches of 21 samples and typical values of visual color thresholds.     

A local and global tour on MOMoT

Software and Systems Modeling - Many model transformation scenarios require flexible execution strategies as they should produce models with the highest possible quality. At the same time,...     

Continuous Improvement Methodology Applied to United Kingdom Academic Library Websites Via National Survey Results

This article analyzes the possibilities of applying Continuous Improvement principles to the management and maintenance of academic library websites. Current practice is mapped onto Continuous Improvement principles, with evidence distilled from a United Kingdom national survey of academic library web practitioners. The survey data informs a website organizational framework and operational model. The framework describes the setting within which library websites are managed, while the model focuses on library specific aspects to the management and development of their site.