Mechanism of BRAF Activation through Biochemical Characterization of the Recombinant Full‐Length Protein

BRAF kinase plays an important role in mitogen‐activated protein kinase (MAPK) signaling and harbors activating mutations in about half of melanomas and in a smaller percentage in many other cancers. Despite its importance, few in vitro studies have been performed to characterize the biochemical properties of full‐length BRAF. Herein, a strategy to generate an active, intact form of BRAF protein suitable for in vitro enzyme kinetics is described. It is shown that purified, intact BRAF protein autophosphorylates the kinase activation loop and this can be enhanced by binding the MEK protein substrate through an allosteric mechanism. These studies provide in vitro evidence that BRAF selectively binds to active RAS and that the BRAF/CRAF heterodimer is the most active form, relative to their respective homodimers. Full‐length BRAF analysis with small‐molecule BRAF inhibitors shows that two drugs, dabrafenib and vemurafenib, can modestly enhance kinase activity of BRAF at low concentration. Taken together, this characterization of intact BRAF contributes to a framework for understanding its role in cell signaling.     

Strain-Rate Effect on Soil Secant Shear Modulus at Small Cyclic Strains

The effects of the shear strain rate = dγ/dt on the secant shear modulus Gs of three clays and three sands at small cyclic shear strain amplitudes γc under simple shear loading conditions are described. The amplitude γc varied between 0.0003 and 0.02% and between 0.0002 and 0.04 %/s. For all six soils Gs increases with , such that the Gs versus log? data plot approximately along a straight line. The slope of this line is αG=strain-rate shear modulus parameter, while its normalized value αG/Gs = =shear strain-rate modulus factor. For the clays tested αG ranges between 2.5 and 7.5 MPa and between 2.0 and 11.5%. For the sandy soils αG ranges between 0.2 and 3.0 MPa and between 0.2 and 6.0%. Both αG and decrease moderately with increasing γc, i.e., the largest αG and were obtained at the smallest γc. For five soils the families of the normalized modulus reduction curves (Gs/Gmax)–log?γc were constructed, such that each curve pertains to a constant . It was found that has essenlially no effect on the shape of the constant-?(Gs/Gmax)–log?γc curve. A brief review of previous experimental studies is included.     

Structural equation model (SEM)-neural network (NN) model for predicting quality determinants of e-learning management systems

The success of e-learning management systems (e-LMSs) such as MOODLE depends on the usage of students as well as instructor acceptance in a virtual learning environment. E-Learning enables instructors to access educational resources to support traditional classroom teaching. This paper attempts to develop a model to understand and predict the effect of individual characteristics (technology experience [TE] and personal innovativeness [PI]) and e-LMS quality determinants (system quality [SYS-Q], information quality, and service quality) on the continuous use of e-LMS by instructors, which is critical to its success. A total of 219 instructors using MOODLE responded to the survey. The structural equation model (SEM) was employed to test the proposed research model. The SEM results showed that SYS-Q, PI, service quality, and TE have a statistically significant influence on continuous usage of e-LMS by instructors. Furthermore, all determinants of the research model were given as input to an NN model to overcome the simplistic nature of the SEM model. The NN model results showed that service quality is the most important predictor of e-learning acceptance followed by SYS-Q, PI, information quality, and TE. This paper attempts to develop a causal and predictive statistical model for predicting instructor e-LMS acceptance.     

The Effect of Methanol on the Micellar Properties of Dodecyltrimethylammonium Bromide (DTAB) in Aqueous Medium at Different Temperatures

The micellar properties of dodecyltrimethylammonium bromide (DTAB) in water and methanol water mixtures at different temperatures have been studied by conductivity and surface tension measurements. The critical micelle concentrations (CMC), degree of ionization (α), standard Gibbs free energy of micellization (), standard enthalpy of micellization (), standard entropy of micellization () and free energy of transfer () were evaluated from conductivity data. The CMC, maximum excess surface concentration ( ), area occupied per surfactant molecule ( ), surface pressure at the CMC ( ), packing parameter (P) and standard free energy interfacial adsorption ) were estimated from surface tension measurements. The CMC of DTAB was found to increase with increasing volume fraction of methanol and increasing temperature. Thermodynamic parameters and surface properties revealed that the addition of methanol changes the relevant physicochemical properties which affect the process of micellization.     

Releasing high aspect ratio SU-8 microstructures using AZ photoresist as a sacrificial layer on metallized Si substrates

This paper presents a successful method for releasing high aspect ratio SU-8 micro-structures by the use of positive photoresist (AZ 4620) as sacrificial layer. The AZ 4620 photoresist sacrificial layer was dissolved by the SU-8 developer (propylene glycol monomethyl ether acetate). Thus, this process reduces the need for complex microfabrication steps and equipments which are otherwise required in traditional methods using metal sacrificial layers. The current method is both cost-effective and time-effective because no additional releasing method or material is needed to remove the fabricated SU-8 structures. Further, the influence of surface energy on the adhesion between Si and SU-8 was demonstrated and metallic thin layer coating on Si was employed to further reduce the lift-off duration. The results obtained showed that the duration for lift-off of SU-8 structures from metal (Al) coated Si substrate is much lower (approximately 90 % time saving) and the surface morphology of the released structures has lesser micropore concentration compared to the process employing bare Si as the substrate. In both processes AZ 4620 was the sacrificial layer whereas the metalized Si substrate could be re-used.