Electron probeX-ray microanalysis for the assessment of homogeneity of candidate reference materials at the nanogram level

A new approach to the assessment of homogeneity for powder samples of candidate reference materials with the help of electron probeX-ray micro-analysis (EPMA) is proposed. It is based on the utilisation of the Kolmogorov—Smirnov statistics coupled with the Akaike Information Criterion in the processing of the quantitative EPMA data. The evaluation of three IAEA candidate reference materials with the described approach is discussed.     

Characterizations of finite classical polar spaces by intersection numbers with hyperplanes and spaces of codimension 2

In this article we show that non-singular quadrics and non-singular Hermitian varieties are completely characterized by their intersection numbers with respect to hyperplanes and spaces of codimension 2. This strongly generalizes a result by Ferri and Tallini [5] and also provides necessary and sufficient conditions for quasi-quadrics (respectively their Hermitian analogues) to be non-singular quadrics (respectively Hermitian varieties).     

Sensitive Spectroscopic Detection of Large and Denatured Protein Aggregates in Solution by Use of the Fluorescent Dye Nile Red

The fluorescent dye Nile red was used as a probe for the sensitive detection of large, denatured aggregates of the model protein β-galactosidase (E. coli) in solution. Aggregates were formed by irreversible heat denaturation of β-galactosidase below and above the protein’s unfolding temperature of 57.4°C, and the presence of aggregates in heated solutions was confirmed by static light scattering. Interaction of Nile red with β-galactosidase aggregates led to a shift of the emission maximum (λ _max) from 660 to 611 nm, and to an increase of fluorescence intensity. Time-resolved fluorescence and fluorescence correlation spectroscopy (FCS) measurements showed that Nile red detected large aggregates with hydrodynamic radii around 130 nm. By steady-state fluorescence measurements, it was possible to detect 1 nM of denatured and aggregated β-galactosidase in solution. The comparison with size exclusion chromatography (SEC) showed that native β-galactosidase and small aggregates thereof had no substantial effect on the fluorescence of Nile red. Large aggregates were not detected by SEC, because they were excluded from the column. The results with β-galactosidase demonstrate the potential of Nile red for developing complementary analytical methods that overcome the size limitations of SEC, and can detect the formation of large protein aggregates at early stages.     

Modelling of Binder-Induced Agglomeration

From the analysis of pendular liquid bridge forces between spherical particles, a model has been developed to predict bridge rupture energies. Whilst this model has been shown to predict the correct trends in certain stages of agglomeration, it is limited by the assumptions of zero contact angle, toroidal bridge geometry, spherical particles and quasi-static rupture. The work described here is aimed at extending the model to more generally applicable conditions using direct measurement of bridge rupture energies between particles down to 3 μm in diameter under different physiochemical conditions. Initial results show that the spreading coefficient of the binder to the particle has a marked effect on the dynamic behaviour of the bridge itself and its subsequent geometry at equilibrium, i.e. for non-zero contact angles theoretical equations tend to over-predict the force of adhesion, whilst for zero contact angles the force of adhesion agrees with that predicted using the Laplace equations for constant curvature. On the other hand, the corrected expression for maximum separation distance shows good agreement with experimental results.     

Hard- and soft-line responses to Pereboom’s four-case manipulation argument

Derk Pereboom has advanced a four-case manipulation argument that, he claims, undermines both libertarian accounts of free action not committed to agent-causation and compatibilist accounts of such action. The first two cases are meant to be ones in which the key agent is not responsible for his actions owing to his being manipulated. We first consider a “hard-line” response to this argument that denies that the agent is not morally responsible in these cases. We argue that this response invites a dialectically uncharitable reading of the argument. We then propose an alternative interpretation; it affirms that, at least prima facie, the manipulated agent in the first two cases is not responsible. Finally, we question Pereboom’s rationale for why the manipulation in these cases subverts responsibility.     

One-cohomology and the uniqueness of the group measure space decomposition of a II1 factor

We provide a unified and self-contained treatment of several of the recent uniqueness theorems for the group measure space decomposition of a II₁ factor. We single out a large class of groups Γ, characterized by a one-cohomology property, and prove that for every free ergodic probability measure preserving action of Γ the associated II₁ factor has a unique group measure space Cartan subalgebra up to unitary conjugacy. Our methods follow closely a recent article of Chifan–Peterson, but we replace the usage of Peterson’s unbounded derivations by Thomas Sinclair’s dilation into a malleable deformation by a one-parameter group of automorphisms.     

Evaluation of Encoded Layer‐By‐Layer Coated Microparticles As Protease Sensors

Proteases are important pharmaceutical targets for new drugs because of their involvement in numerous disease processes. This study evaluates whether photophysically encoded microparticles carrying fluorescently labeled protease substrates (peptides) at their surface show potential for detecting proteases in a sample. Layer‐by‐layer (LbL) polyelectrolyte coatings, containing a red‐labeled peptidic trypsin substrate, are carefully designed and applied at the surface of the encoded microparticles. The peptide‐loaded LbL coatings lose their red fluorescence upon incubation in a trypsin solution, indicating that LbL‐coated microparticles show potential to screen for the presence of active proteases in biological samples.     

Modulation of Dendritic Cells by Lipid Grafted Polyelectrolyte Microcapsules

Polyelectrolyte microcapsules are fabricated by layer‐by‐layer deposition of dextran sulfate and poly‐L ‐arginine layers at the surface of calcium carbonate template microparticles followed by core removal to produce hollow microcapsules. In the context of vaccination, these biodegradable LbL capsules emerge as promising antigen carriers and are believed to have potential for the co‐delivery of antigens and immunomodulators associated within the same particle to enhance and steer the type of immune response. To this end, it is shown that LbL microcapsules can be functionalized at their surface with lipid layers containing immunopotentiators of lipid nature. The potency of the different lipid modified microcapsules to activate dendritic cells (DCs) is demonstrated by increased expression levels of the migration marker CCR7 and the maturation markers CD40 and CD86. Additionally, the DCs cytokine secretion profile is evaluated. The findings reveal that the lipid grafted microcapsules are superior to non‐modified microcapsules in DC activation and suggest their potential as immune modulating antigen delivery systems.     

Simultaneous MR-Compatible Emission and Transmission Imaging for PET Using Time-of-Flight Information

Quantitative positron emission tomography (PET) imaging relies on accurate attenuation correction. Predicting attenuation values from magnetic resonance (MR) images is difficult because MR signals are related to proton density and relaxation properties of tissues. Here, we propose a method to derive the attenuation map from a transmission scan. An annulus transmission source is positioned inside the field-of-view of the PET scanner. First a blank scan is acquired. The patient is injected with FDG and placed inside the scanner. 511-keV photons coming from the patient and the transmission source are acquired simultaneously. Time-of-flight information is used to extract the coincident photons originating from the annulus. The blank and transmission data are compared in an iterative reconstruction method to derive the attenuation map. Simulations with a digital phantom were performed to validate the method. The reconstructed attenuation coefficients differ less than 5% in volumes of interest inside the lungs, bone, and soft tissue. When applying attenuation correction in the reconstruction of the emission data a standardized uptake value error smaller than 9% was obtained for all tissues. In conclusion, our method can reconstruct the attenuation map and the emission data from a simultaneous scan without prior knowledge about the anatomy or the attenuation coefficients of the tissues.     

Topology selection for high-precision Vernier digital-to-time converters in standard CMOS

This paper presents two architectures that apply the Vernier delay line principle to the field of digital-to-time conversion. Both architectures are compared in terms of variability, power consumption, and area. The results show that the optimal architecture depends on the required delay resolution, on technology parameters, and on the relative importance given to power and area. If the required resolution is much smaller than the unit delay and single-shot precision is important, a topology using a matrix of delay elements provides a better power-mismatch tradeoff. If the required resolution is modest, if there is a stringent area spec, or if the focus is on linearity rather than single-shot precision, a dual delay line topology is to be preferred. The paper also derives a Pelgrom-like mismatch law for propagation delay, which can be used in the design of different types of circuits and will become more valid in future CMOS generations.