Development of the First Oral Bioprecursors of Bis‐alkylguanidine Antimalarial Drugs

Plasmodium falciparum is responsible of the most severe form of malaria, and new targets and novel chemotherapeutic scaffolds are needed to fight emerging multidrug‐resistant strains of this parasite. Bis‐alkylguanidines have been designed to mimic choline, resulting in the inhibition of plasmodial de novo phosphatidylcholine biosynthesis. Despite potent in vitro antiplasmodial and in vivo antimalarial activities, a major drawback of these compounds for further clinical development is their low oral bioavailability. To solve this issue, various modulations were performed on bis‐alkylguanidines. The introduction of N‐disubstituents on the guanidino motif improved both in vitro and in vivo activities. On the other hand, in vivo pharmacological evaluation in a mouse model showed that the N‐hydroxylated derivatives constitute the first oral bioprecursors in bis‐alkylguanidine series. This study paves the way for bis‐alkylguanidine‐based oral antimalarial agents targeting plasmodial phospholipid metabolism.     

Water retention and gas relative permeability of two industrial concretes

This experimental study aims at identifying the water retention properties of two industrial concretes to be used for long term underground nuclear waste storage structures. Together with water retention, gas transfer properties are identified at varying water saturation level, i.e. relative gas permeability is assessed directly as a function of water saturation level S_w. The influence of the initial de-sorption path and of the subsequent re-saturation are analysed both in terms of water retention and gas transfer properties. Also, the influence of concrete microstructure upon water retention and relative gas permeability is assessed, using porosity measurements, analysis of the BET theory from water retention properties, and MIP. Finally, a single relative gas permeability curve is proposed for each concrete, based on Van Genuchten–Mualem's statistical model, to be used for continuous modelling approaches of concrete structures, both during drying and imbibition.     

Scheduling of open-pit phosphate mine extraction

Open-pit deposits are often characterised by a stack of layers of different geological nature. Some layers are worthless while the ore of the others is of a varying economic value depending on grade. To reach a layer, it is necessary to have first removed the upper layers above the extraction zone. This action results in uncovering the layer in this particular place and in facilitating access to the layers below. This extraction process involves a series of 2–7 basic operations; each one is performed by a machine, some of which are able to perform up to three different operations. Ensuring the consistency of mining extraction scheduling over a few months, in order to meet known or forecast demand, is a challenging task. A mining extraction model based on mathematical programming is proposed but it is hardly usable, due to its size. Therefore, a model based on a Discrete Event Simulation, is created to test how ore supplies are affected by the tactical and operational decisions relating to the choice of parcels to be processed and to the allocation of machines to the different basic operations.     

Typing artifacts in megamodeling

Model management is essential for coping with the complexity introduced by the increasing number and varied nature of artifacts involved in model-driven engineering-based projects. Global model management (GMM) addresses this issue by enabling the representation of artifacts, particularly transformation composition and execution, within a model called a megamodel. Type information about artifacts can be used for preventing type errors during execution. Built on our previous work, in this paper we present the core elements of a type system for GMM that improves its original typing approach and enables both typechecking and type inference on artifacts within a megamodel. This type system is able to deal with non-trivial situations such as the use of higher order transformations. We also present a prototypical implementation of such a type system.     

Characterization and properties of blended cement matrices containing activated bamboo leaf wastes

The worldwide production of bamboo generates large volumes of leaf wastes, which are deposited in landfills or burned in an uncontrolled manner, with negative effects in the environment. The ash obtained by calcining of the bamboo leaf waste, shows good qualities as supplementary cementing material for the production of blended cements.The current paper shows a detailed scientific study of a Brazilian bamboo leaf ash (BLA) calcined at 600 °C in small scale condition, by using different techniques (XRF, XRD, SEM/EDX, FT–IR, TG/DTG) and technical study in order to analyse the behaviour of this ash in blended cements elaborated with 10% and 20% by mass of BLA. The results stated that this ash shows a very high pozzolanic activity, with a reaction rate constant K of the order of 10^?1/h and type I CSH gel was the main hydrated phase obtained from pozzolanic reaction. The BLA blended cements (10% and 20%) complied with the physical and mechanical requirements of the existing European standards.     

Synthesis of Tribologically Favorable Coatings for Hot Extrusion Tools by Suspension Plasma Spraying

Up to now, no coating systems have been marketed in the field of direct hot extrusion, which provide both surface protection of the parts in contact with the billet (i.e., container and die) as well as a significant reduction of the frictional losses induced by the billet passing over the container walls. To dispense with the use of lubricants and to enhance the usable forming capacity and therefore the efficiency of the process, different oxide ceramics were prepared in one suspension and plasma sprayed to produce coatings. The aim was to reach a sufficient level of feedstock mixing to obtain deterministic solid solutions of the oxide phases in coatings resulting in a reduction of their coefficient of friction under dry sliding conditions. To achieve this objective, the high specific surface area of nanosized feedstock with primary particle sizes below 100?nm was used. By means of x-ray diffraction it could be proven, that the desired phases could be synthesized to varying ratios regarding the different coating systems considered here. Besides the experimental work, the fundamentals of the mixing process of different oxides are discussed with regard to the crystallographic aspects.     

Antennas for next generation mobile communications

In future mobile communications many antennas will coexist on the device. This creates a number of problems related to bandwidth, efficiency, and correlation. Remedies are discussed in the paper, and attention is called to the promising area of adaptive matching, which also can solve problems related to the user.     

Enhancing the efficiency of alternating current driven organic light-emitting devices by optimizing the operation frequency

We report efficient and bright organic light-emitting devices operated by capacitive energy coupling. In this approach, the organic layers are enclosed between sputter-deposited hafnium dioxide layers to prevent charge carrier injection. When a sinusoidal voltage signal is applied to the electrodes, the devices emit bright green light whereas no detectable emission is generated upon application of a constant voltage. The efficiency of the process depends heavily on the frequency of the applied voltage signal. By optimizing the driving scheme, a record luminous efficacy for AC driven OLEDs of 2.7 lm/W at 500 cd/m² is achieved.     

Capillary self-alignment of polygonal chips: a generalization for the shift-restoring force

Capillary-driven self-alignment using droplets is currently extensively investigated for self-assembly and microassembly technology. In this technique, surface tension forces associated to capillary pinning create restoring forces and torques that tend to bring the moving part into the alignment. So far, most studies have addressed the problem of square chip alignment on a dedicated patch of a wafer, aiming to achieve 3D microelectronics. In this study, we investigate the shift-restoring forces for more complex moving parts such as regular—convex and non-convex—polygons and regular polygons with regular polygonal cavities. A closed-form approximate expression is derived for each of these polygonal geometries; this expression agrees with the numerical results obtained with the Surface Evolver software. For small shifts, it is found that the restoring force does not depend on the shift direction or on the polygonal shape. In order to tackle the problem of microsystem packaging, an extension of the theory is done for polygonal shapes pierced with connection vias (channels), and a closed form of the shift-restoring force is derived for these geometries and again checked against the numerical model. In this case, the restoring force depends on the shift direction. Finally, a non-dimensional number, the shift number, is proposed that indicates the isotropic or anisotropic behavior of the chip according to the shift direction.