Structural Cues for Understanding eEF1A2 Moonlighting

Spontaneous mutations in the EEF1A2 gene cause epilepsy and severe neurological disabilities in children. The crystal structure of eEF1A2 protein purified from rabbit skeletal muscle reveals a post-translationally modified dimer that provides information about the sites of interaction with numerous binding partners, including itself, and maps these mutations onto the dimer and tetramer interfaces. The spatial locations of the side chain carboxylates of Glu301 and Glu374, to which phosphatidylethanolamine is uniquely attached via an amide bond, define the anchoring points of eEF1A2 to cellular membranes and interorganellar membrane contact sites. Additional bioinformatic and molecular modeling results provide novel structural insight into the demonstrated binding of eEF1A2 to SH3 domains, the common MAPK docking groove, filamentous actin, and phosphatidylinositol-4 kinase IIIβ. In this new light, the role of eEF1A2 as an ancient, multifaceted, and articulated G protein at the crossroads of autophagy, oncogenesis and viral replication appears very distant from the “canonical” one of delivering aminoacyl-tRNAs to the ribosome that has dominated the scene and much of the thinking for many decades.     

The generalized discrete ‐centroid problem

The ‐centroid problem or leader–follower problem is generalized considering different customer choice rules where a customer may use facilities belonging to different firms, if the difference in travel distance (or time) is small enough. Assuming essential goods, some particular customer choice rules are analyzed. Linear programming formulations for the generalized ‐medianoid and ‐centroid problems are presented and an exact solution approach is applied. Some computational examples are included.     

Highly Ionized Arc He Plasma: Nonequilibrium,Nonideality, and Kinetics

High Temperature - Experimental findings suggest that a strongly ionized, arc He plasma of atmospheric pressure does not exist in the state of the local thermodynamic equilibrium (LTE) expected for...     

Nonhydrolyzable Heptose Bis- and Monophosphate Analogues Modulate Pro-inflammatory TIFA-NF-κB Signaling

d -Glycero-d -manno-heptose-1β,7-bisphosphate (HBP) and d -glycero-d -manno-heptose-1β-phosphate (H1P) are bacterial metabolites that were recently shown to stimulate inflammatory responses in host cells through the activation of the TIFA-dependent NF-κB pathway. To better understand structure-based activity in relation to this process, a family of nonhydrolyzable phosphonate analogues of HBP and H1P was synthesized. The inflammation modulation by which these molecules induce the TIFA-NF-κB signal axis was evaluated in vivo at a low-nanomolar concentration (6 nM) and compared to that of the natural metabolites. Our data showed that three phosphonate analogues had similar stimulatory activity to HBP, whereas two phosphonates antagonized HBP-induced TIFA-NF-κB signaling. These results open new horizons for the design of pro-inflammatory and innate immune modulators that could be used as vaccine adjuvant.     

Software assurance practices for mobile applications

Mobile software applications have to cope with a particular environment that involves small size, limited resources, high autonomy requirements, competitive business models and many other challenges. To provide development guidelines that respond to these needs, several practices have been introduced; however, it is not clear how these guidelines may contribute to solve the issues present in the mobile domain. Furthermore, the rapid evolution of the mobile ecosystem challenges many of the premises upon which the proposed practices were designed. In this paper, we present a survey of the literature on software assurance practices for mobile applications, with the objective of describing them and assessing their contribution and success. We identified, organized and reviewed a body of research that spans in three levels: software development processes, software product assurance practices, and software implementation practices. By carrying out this literature survey, we reviewed the different approaches that researchers on Software Engineering have provided to address the needs that raise in the mobile software development arena. Moreover, we review the evolution of these practices, identifying how the constant changes and modernization of the mobile execution environment has impacted the methods proposed in the literature. Finally, we introduced discussion on the application of these practices in a real productive setting, opening an area for further research that may determine if practitioners have followed the proposed assurance paradigms.     

Ga-doped IZO films obtained by magnetron sputtering as transparent conductors for visible and solar applications

C-axis textured thin films of gallium-doped indium zinc oxide (GIZO) with a 2% ratio of Ga/Zn, were obtained via RF-magnetron sputtering with high transparency and electrical conductivity. A Box-Behnken response surface design was used to evaluate the effects of the deposition parameters (In₂O₃ target power, deposition time, and substrate temperature) on the chemical composition, optical, electrical, and structural properties of the GIZO films. The optical constants and the electrical properties were obtained using optical models. The GIZO stoichiometry, and therefore the In/Zn atomic ratio, affected the crystallinity, crystalline parameters, band gap, and charge carrier mobility of the GIZO films. The charge carrier density was related to the change in the crystalline parameters of the hexagonal structure and the In/Zn atomic ratio. The best electrical conductivity values (1.75?×?10³ Ω^?1 cm^?1) were obtained for GIZO films with In/Zn ratio ≥?1. Several figures of merit (FOM) defined for the visible and solar regions were comparatively used to select the optimal In/Zn atomic ratio that provided the best balance between the conductivity and the transparency. The optimal In/Zn ratio was in a range of 0.85–0.90 for the GIZO films.     

Design guidelines for titania-silica-alumina ceramics with tuned anatase to rutile transformation

Titania-based ceramics with adjustable anatase-rutile fractions were obtained by milling of anatase, quartz and corundum precursors, uniaxial pressing and firing at 1100?°C. The influence of silica and alumina, combined with milling time and compaction pressure, was studied by design of experiments. The L9 orthogonal array with a three-level noise factor was employed. Firing of pure titania at 1100?°C yielded complete anatase to rutile transformation (ART), whereas stabilized samples show that an optimum amount of 9% silica and 33% alumina reduces phase transformation to only about 5?wt% rutile. An extended correlation matrix combined with analysis of variance (ANOVA) was applied to assess the combined effects of quartz, alumina, milling time and uniaxial compressing pressure on relative density, and anatase to rutile transformation. Results show absence of ART after milling, and controlled partial conversion of anatase to rutile after firing. Very good fitting was obtained by multivariate analysis on considering first and second order terms for dependence on silica contents and interactions between silica and each of the remaining factors, including milling time. This empirical dependence could be interpreted on a sound physicochemical basis, allowing the prediction of suitable compositions and processing conditions to obtain rutile-free samples by conventional ceramic processing, and to design ceramic samples with controlled fractions of anatase and rutile.     

Intrinsic CFRP-metal-hybrids with rubber interface for the improvement of the damping behaviour

This paper presents an integrated passive damping approach in hybrid metal-CFRP parts for structural applications. In this concept a viscoelastic material is embedded in the joint zone of the hybrid component. To examine the connection strength single-lap-joint specimens were produced and tested and the influence of the used material combinations, different surface structures, and different process parameters i.e. the moment of cross-linking were evaluated. Afterwards, the metal-CFRP hybrids were tested in quasi-static tests to assess their connection strength and failure behaviour. Dynamic cyclic tensile tests with step-wise increased loading conditions were performed to determine the specimens damping behaviour and to estimate their fatigue performance. Finally, these results are compared to a state of the art metal-CFRP hybrid with rivets connecting both materials.