Hydrogenation of p‐Nitrophenol to p‐Aminophenol as a Test Reaction for the Catalytic Activity of Supported Pt Catalysts

Hydrogenation of p‐nitrophenol (PNP) to p‐aminophenol (PAP) using NaBH₄ as a reducing agent was studied as a test reaction for determining the catalytic activity of supported Pt catalysts. The initial reaction rate, which is accessible within less than 10 min via online UV‐vis spectroscopy at room temperature, ambient pressure, and in water as solvent, was applied as measure for catalytic activity. For three Pt catalysts supported on porous SiO₂, porous glass, and Al₂O₃, respectively, significant differences in the catalytic activity by almost one order of magnitude were observed. However, especially in the case of very active catalysts, limitations of the reaction by internal or external mass transfer have to be considered.     

Conjugation to Albumin‐Binding Molecule Tags as a Strategy to Improve Both Efficacy and Pharmacokinetic Properties of the Complement Inhibitor Compstatin

The compstatin family of complement inhibitors has shown promise in various immuno‐inflammatory disorders. Although recent analogues show beneficial pharmacokinetics, further extension of the plasma half‐life is expected to benefit systemic application of these peptidic inhibitors. We therefore synthesized conjugates of compstatin analogues and albumin‐binding molecules (ABM) to increase circulatory residence. Equilibrium dialysis in complement‐depleted serum showed a marked increase in plasma protein binding from <8 % to >99 % for a resulting chimera (ABM2‐Cp20). Further analysis confirmed interaction with albumin from different species, primarily via site II. Importantly, ABM2‐Cp20 bound 20‐fold stronger to its target protein C3b (K_D=150 pM ) than the parent peptide. Kinetic and in silico analysis suggested that ABM2 occupies a secondary site on C3b and improves the dissociation rate via additional contacts. Addition of an ABM modifier thereby not only improved plasma protein binding but also produced the most potent compstatin analogue to date with potential implications for the treatment of systemic complement‐related diseases.     

Advantages and challenges with using hypoxic air venting as fire protection

The use of hypoxic air venting system as fire protection is increasing and is sometimes used to replace traditional extinguishing systems. An oxygen level of 15% is generally used because a lower concentration could pose serious health risks. On the request of the Swedish Radiation Safety Authority, a literature review was conducted to determine advantages and challenges with the system and further research needs. The main advantages with a reduced oxygen environment are the reduced probability of ignition and lowered heat release rate. However, at 15% oxygen level, risk for fire still exists, and the system cannot be seen as an alternative to extinguishing systems. Reduced oxygen environment also results in higher production rates of soot and smoke, and there is limited knowledge regarding the effect of fuel configuration and fire behavior of products. In addition, a first evaluation of the test method specified in the hypoxic air venting standards was carried out through testing. The testing showed that the particleboard passed the test criteria at normal atmosphere even though it is commonly known that a particleboard burns in normal air. It is concluded that the test method has deficiencies, and there is clearly a need for development of the test method to guarantee safety levels. © 2013 The Authors. Fire and Materials published by John Wiley & Sons, Ltd.     

An Improved Technique for the Rapid Chemical Characterisation of Bacterial Terpene Cyclases

A derivative of the pET28c(+) expression vector was constructed. It contains a yeast replication system (2μ origin of replication) and a yeast selectable marker (URA3), and can be used for gene cloning in yeast by efficient homologous recombination, and for heterologous expression in E. coli. The vector was used for the expression and chemical characterisation of three bacterial terpene cyclases.     

Mechanism of Action of AminoCBIs: Highly Reactive but Highly Cytotoxic Analogues of the Duocarmycins

Duocarmycins are highly cytotoxic natural products that have potential for development into anticancer agents. Herein we describe proposed but previously unidentified NH analogues of the DNA‐alkylating subunit and characterise these by solvolysis studies, NMR and computational modelling. These compounds are shown to be the exclusive intermediates in the solvolysis of their seco precursors and to possess very similar structural features to the widely studied O‐based analogues, apart from an unusually high basicity. The measured pK_a of 10.5 implies that the NH compounds are fully protonated under physiological conditions. Remarkably, their extremely high reactivity (calculated hydrolysis rate 10⁸ times higher for protonated NH compared to the neutral O analogue) is still compatible with potent cytotoxicity, provided the active species is formed in the presence of cells. These surprising findings are of relevance to the design of duocarmycin‐based tumour‐selective therapies.     

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.     

Slip Length Measurements Using µPIV and TIRF-Based Velocimetry

The goal of this paper is to review progress (mostly recent) made in micro and nanovelocimetry, focusing on two techniques: µPIV (microparticle image velocimetry) and nanoPTV (nanoparticle tracking velocimetry). The paper focuses on the measurement of slippage (taken as a benchmark for these techniques), concentrating on work done in our group. We review the developments of µPIV that led, in the last ten years, to the achievement of 100 nm accuracy in the measurement of slip lengths. Later, this approach was complemented by nanoPTV, which recently obtained ±5 nm precision. Here, we also mention recent application of these techniques toward better characterization of microgel and polymer flows. As a whole, the two techniques have conveyed valuable information on flow behavior within and close to the boundaries of microchannels, on the importance of wetting, and on the role of surface heterogeneities. µPIV is commercially available but nanoPTV is not mature. Interesting instrumental developments are expected in the future for the latter technique.     

A new double imaging velocity focusing coincidence experiment: i(2)PEPICO

The vacuum ultraviolet (VUV) beamline of the Swiss Light Source has been upgraded after two years of operation. A new, turntable-type monochromator was constructed at the Paul Scherrer Institut, which allows for fast yaw-alignment as well as quick grating change and exchange. In addition to the original imaging photoelectron photoion coincidence endstation (iPEPICO), a second, complementary double imaging setup (i(2)PEPICO) has been built. Volatile samples can be introduced at room temperature or in a molecular beam, a pyrolysis source allows for radical production, and non-volatile solids can be evaporated in a heated cell. Monochromatic VUV radiation ionizes the sample and both photoelectrons and photoions are velocity map imaged onto two fast position sensitive detectors and detected in delayed coincidence. High intensity synchrotron radiation leads to ionization rates above 10(5) s(-1). New data acquisition and processing approaches are discussed for recording coincidence processes at high rates. The setup is capable of resolving pulsed molecular beam profiles and the synchrotron time structure temporally. The latter is shown by photoelectron autocorrelation, which displays both the 1.04 MHz ring clock frequency as well as resolving the micro-pulses with a separation of 2 ns. Kinetic energy release analysis on the dissociative photoionization of CF(4) indicates a dissociation mechanism change in the Franck-Condon allowed energy range of the first ion state.     

Development of an interlocked nail for segmental defects in the rabbit tibia

Previous animal models have been developed to study intramedullary nailing for challenging segmental defects in the tibia. In large animals, interlocked nail fixation created a stable environment suitable to study new bone growth technologies placed in the defect. To our knowledge, there are no comparable interlocked tibial defect models for the rabbit in which new technologies could be evaluated. Such a model would be helpful since the rabbit is a popular initial model for orthopedic research studies owing to its wide availability and low cost. While numerous studies have nailed the rabbit tibia, all were non-locked implants that allowed some degree of instability between the fracture fragments. In addition, the non-locked nails were constructed of stainless steel, whereas human nails are increasingly made from titanium alloy. In the current study, an interlocked titanium nail was developed for the rabbit tibia. It was implanted in cadaver tibiae and subjected to fatigue cycling in combined compression and bending at physiologic levels to 21,061 cycles. This duration is estimated to represent 12 weeks of gait by the animal. Before and after fatigue cycling, monotonic testing was performed in compression and bending at physiologic levels. The intact contralateral limbs served as controls. All limbs completed the cycling; the instrumented limbs exhibited interfragmentary cyclic strain amplitudes during fatigue (616 +/- 139 micro-strain), which was significantly greater than the control limbs (136 +/- 35 microstrain). Monotonic strain amplitudes for the test limbs in bending and compression were 4839 +/- 1028 and 542 +/- 122 microstrain, respectively; corresponding values for the control bones were 407 +/- 118 and 95 +/- 38 microstrain, respectively. These data are similar to those presented in prior studies in larger bone models. The current study presents one method for interlocked nail fixation for this complex tibial shaft fracture in a small animal.     

Gas flow between coaxial tubes: impedance to gas flow in an endotracheal tube increases with a catheter within

The insertion of a suction catheter or a bronchoscope down an endotracheal tube increases the resistance to gas flow down the tube. The extent to which this occurs depends on the relative diameters of the endotracheal tube and the coaxially introduced catheter. This study utilises a laboratory model to quantify this effect, using a steady flow down an annulus between two tubes whose long axes lie co-axially. Two diameters of an endotracheal tube were modelled to represent flow down adult and neonatal endotracheal tubes; these were of internal diameter (d(o)) 6.3 mm and 3.2 mm, and of length (L) 555 mm. A steady flow of air was generated to pass through the model 'endotracheal' tube. Flowrates were calculated to give Re of approximately 5000 for the larger endotracheal tube, and of approximately 1300 for the smaller. These values correspond to clinically appropriate flowrates in adult and neonatal patients, respectively. The pressure drop deltaPo down the endotracheal tube was measured initially without any obstruction, using a calibrated pressure transducer. Catheters of diameter (d(i)) 0.8 mm, 1.6 mm, and 3.2 mm were introduced into the larger diameter endotracheal tube, while catheters of 0.8 mm and 1.6 mm were introduced into the smaller one, and flow was restored to its original value. The pressure drops deltaP down the endotracheal tubes were measured with the catheters introduced a length 'x' into the tube, to x = L/2 and to x = L. Results are compared with a theoretical calculation on the basis of laminar flow for concentric tubes. If a sampling tube or suction catheter is used down the length of an infant's endotracheal tube, the results show that for most values of do/di, there is a significant rise in deltaP/deltaPo. Where a flexible bronchoscope is used down an endotracheal tube or a telescope down a rigid bronchoscope, the value of deltaP/deltaP(o) may also increase unacceptably where d(o)/d(i) is low. The results show that for equal d(o)/d(i), and equal values of x, deltaP/deltaPo are lower for higher values of Re than for lower; and that for lower values of Re there is a more rapid increase in deltaP/deltaPo as x increases, than for higher Re, especially at low values of d(o)/d(i). This result quantifiably confirms clinical experience; that care must be taken in introducing a catheter down a neonatal endotracheal tube. Deviation of these results from the theoretical calculation is less for the smaller Reynolds numbers and smaller values of d(o)/d(i), because under these conditions the flow is more likely to be laminar, with a greater degree of concentricity.