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.     

Performance Study of a Closed-Type Heat Pump Tumble Dryer Using a Simulation Model and an Experimental Set-Up

In the interests of competitiveness, manufactures of tumble dryers are seeking to reduce both their electricity use and the drying time. This study examines how the cylinder volume of the compressor and the total heat transfer of the condenser influence the drying time and electricity use in a heat pump tumble dryer. A transient simulation model was developed and compared to an experimental set-up with good similarity. The simulations show that increasing the cylinder volume of the compressor by 50% decreases the drying time by 14% without using more electricity.     

Creep compliance mapping by atomic force microscopy

We present a method for mapping the spatial distribution of viscoelastic properties of heterogeneous samples using the atomic force microscope (AFM). By applying a force step load protocol to induce time dependent sample indentations we measured the local creep compliance of the sample. The creep compliance was quantified in terms of the standard linear solid model to give maps of the instant glassy modulus, the equilibrium rubbery modulus, and the retardation time. To reduce the influence of plastic deformations, the sample was preformed with an initial preload step. Different polymer samples with a homogeneous or a heterogeneous material composition on a microscopic scale were investigated.     

Friction Coefficient Measurement of Hydrogel Materials on Living Epithelial Cells

Soft biomaterials are often used in applications that involve contact and relative motion against biological tissues, as well as complicated and variable environments. The friction coefficient of these contacts involving living human cells is of key importance in the analysis and success of these devices. This work measures the contacting friction coefficient between soft hydrogel biomaterial surfaces against live human corneal epithelial cells using a custom micro-tribometer. The friction coefficients were of the order of μ = 0.03 for contacts that did not cause gross destruction of the cell layer. Damage to the confluent cell layer was assessed using a Trypan blue stain with optical microscopy. This damage was quantified statistically using image-processing software. The damage was also correlated to in situ friction measurements, with the lowest friction values seen on undamaged cells and higher friction on damaged regions.     

Investigating the cutting phenomena in free-form milling using a ball-end cutting tool for die and mold manufacturing

This paper presents an investigation of nonplanar tool-workpiece interactions in free-form milling using a ball-end cutting tool, a technique that is widely applied in the manufacturing of dies and molds. The influence of the cutting speed on the cutting forces, surface quality of the workpiece, and chip formation was evaluated by considering the specific alterations of the contact between tool-surface along the cutting time. A trigonometric equation was developed for identifying the tool-workpiece contact along the toolpath and the point where the tool tip leaves the contact with the workpiece. The experimental validation was carried out in a machining center using a carbide ball-end cutting tool and a workpiece of AISI P20 steel. The experimental results demonstrated the negative effect of the engagement of the tool tip into the cut on machining performance. The length of this engagement depends on the tool and workpiece curvature radii and stock material. When the tool tip center is in the cut region, the material is removed by shearing together with plastic deformation. Such conditions increase the cutting force and surface roughness and lead to an unstable machining process, what was also confirmed by the chips collected.     

Electron microscopy studies of the thermal stability of gold nanoparticle arrays

A series of monolayer protected gold nanoparticle colloidal solutions have been prepared with average sizes in the 2–15nm range. If a drop of such a colloidal suspension is deposited onto a Si₃N₄ substrate and the solvent allowed to evaporate, the particles have a tendency to self-assemble into monolayer rafts with varying degrees of structural order depending on the initial mono-dispersity of the particles. The thermal stability of these selfassembled gold nanoparticle rafts as a function of particle size, heating method, heating rate and ligand identity have been assessed in this study. In-situ TEM studies show that sub-8nm Au nanoparticles on Si₃N₄ have a tendency to coarsen upon slow heating, whereas those comprised of larger particles exhibit densification. Increasing the heating rate for the smaller particles promoted densification, forcing them to form highly interconnected string-like structures. Finally, rafts of sub-4nm alkanethiol protected Au nanoparticles are shown to sinter spontaneously under ambient conditions at room temperature on the timescale of several months. This unexpected effect may have important implications for the long term structural stability of any device constructed from sub-4nm gold nanoparticles.     

Investigation of TBCs on turbine blades by photoluminescence piezospectroscopy

Thermal barrier coating (TBC) blade specimens with Pt diffusion bond coats were subjected to thermal cycling with periodic measurements of the residual stress in the thermally grown oxide (TGO) using photoluminescence piezospectroscopy. Two distinct stress levels were generally found to coexist in the probed volume, i.e. a high stress (～4 GPa) and a low stress (～500 MPa) level. Both the high and low stress levels were independent of the curvature of the blade surface, in agreement with numerical modelling based on a composite cylinder stress model. The relative contributions of the two stress levels appear to be correlated with the θ-Al₂O₃ content of the TGO, which was dependent on the position on the blade. The TBCs tended to fail along the TGO/bond coat interface in thermal cycling. This was modified by the presence of mixed transition metal oxides in the TGO. The results are interpreted in terms of a likely failure mechanism.