Introduction: Vagueness and Ontology

The article introduces a special issue of the journal Metaphysica on vagueness and ontology. The conventional view has it that all vagueness is semantic or representational. Russell, Dummett, Evans and Lewis, inter alia, have argued that the notion of “ontic” or “metaphysical” vagueness is not even intelligible. In recent years, a growing minority of philosophers have tried to make sense of the notion and have spelled it out in various ways. The article gives an overview and relates the idea of ontic vagueness to the unquestioned phenomenon of fuzzy spatiotemporal boundaries and to the associated “problem of the many”. It briefly discusses the question of whether ontic vagueness can be spelled out in terms of “vague identity”, emphasizes the often neglected role of the difference between sortal and non-sortal ontologies and suggests a deflationary answer to the ill-conceived question of whether the “ultimate source” of vagueness lies either in language or in the world.     

Protecting‐Group‐Controlled Enzymatic Glycosylation of Oligo‐N‐Acetyllactosamine Derivatives

We describe a chemoenzymatic strategy that can give a library of differentially fucosylated and sialylated oligosaccharides starting from a single chemically synthesized tri‐N‐acetyllactosamine derivative. The common precursor could easily be converted into 6 different hexasaccharides in which the glucosamine moieties are either acetylated (GlcNAc) or modified as a free amine (GlcNH₂) or Boc (GlcNHBoc). Fucosylation of the resulting compounds by a recombinant fucosyl transferase resulted in only modification of the natural GlcNAc moieties, providing access to 6 selectively mono‐ and bis‐fucosylated oligosaccharides. Conversion of the GlcNH₂ or GlcNHBoc moieties into the natural GlcNAc, followed by sialylation by sialyl transferases gave 12 differently fucosylated and sialylated compounds. The oligosaccharides were printed as a microarray that was probed by several glycan‐binding proteins, demonstrating that complex patterns of fucosylation can modulate glycan recognition.     

Fluorescence monitoring of microchip capillary electrophoresis separation with monolithically integrated waveguides

Using femtosecond laser writing, optical waveguides were monolithically integrated into a commercial microfluidic lab-on-a-chip device, with the waveguides intersecting a microfluidic channel. Continuous-wave laser excitation through these optical waveguides confines the excitation window to a width of 12 microm, enabling high-resolution monitoring of the passage of different types of fluorescent analytes when migrating and being separated in the microfluidic channel by microchip capillary electrophoresis. Furthermore, we demonstrate on-chip-integrated waveguide excitation and detection of a biologically relevant species, fluorescently labeled DNA molecules, during microchip capillary electrophoresis. Well-controlled plug formation as required for on-chip integrated capillary electrophoresis separation of DNA molecules, and the combination of waveguide excitation and a low limit of detection, will enable monitoring of extremely small quantities with high spatial resolution.     

Metabolism of methylstenbolone studied with human liver microsomes and the uPA+/+‐SCID chimeric mouse model

Anti‐doping laboratories need to be aware of evolutions on the steroid market and elucidate steroid metabolism to identify markers of misuse. Owing to ethical considerations, in vivo and in vitro models are preferred to human excretion for nonpharmaceutical grade substances. In this study the chimeric mouse model and human liver microsomes (HLM) were used to elucidate the phase I metabolism of a new steroid product containing, according to the label, methylstenbolone. Analysis revealed the presence of both methylstenbolone and methasterone, a structurally closely related steroid. Via HPLC fraction collection, methylstenbolone was isolated and studied with both models. Using HLM, 10 mono‐hydroxylated derivatives (U1–U10) and a still unidentified derivative of methylstenbolone (U13) were detected. In chimeric mouse urine only di‐hydroxylated metabolites (U11–U12) were identified. Although closely related, neither methasterone nor its metabolites were detected after administration of isolated methylstenbolone. Administration of the steroid product resulted mainly in the detection of methasterone metabolites, which were similar to those already described in the literature. Methylstenbolone metabolites previously described were not detected. A GC‐MS/MS multiple reaction monitoring method was developed to detect methylstenbolone misuse. In one out of three samples, previously tested positive for methasterone, methylstenbolone and U13 were additionally detected, indicating the applicability of the method. Copyright © 2014 John Wiley & Sons, Ltd.     

Linear solvation energy relationships of anionic dimeric surfactants in micellar electrokinetic chromatography I. Effect of the length of a hydrophobic spacer

The influence of the length of a flexible hydrophobic spacer on the selectivity of anionic dimeric surfactants was investigated. Disodium 1,omega-bis(decyloxymethyl)-dioxa alkane-1,omega disulfates with a spacer containing an ethylene, butylene, hexylene, octylene, decylene or dodecylene group were synthesized, and four of these were evaluated for use in micellar electrokinetic chromatography (MEKC) via linear solvation energy relationships (LSERs). There were no significant differences in the system constants of these surfactants, indicating that their micelles all have a very similar interface with the aqueous phase, regardless of the length of the hydrophobic spacer. Compared to sodium dodecylsulfate (SDS), these dimeric surfactants are slightly more cohesive, interact better with polarizable compounds, and are somewhat better hydrogen bond acceptors and worse hydrogen bond donors, while there is no difference in dipolarity. The critical micelle concentrations (CMCs) of these surfactants were in the order of 1mM, except for the dimeric surfactant with a spacer containing an ethylene group, which had a CMC <0.03 mM.     

A Multiscale Network Model for Simulating Moisture Transfer Properties of Porous Media

A multiscale network model is presented to model unsaturated moisture transfer in hygroscopic capillary-porous materials showing a broad pore-size distribution. Both capillary effects and water sorption phenomena, water vapour and liquid water transfer are considered. The multiscale approach is based on the concept of examining the porous space at different levels of magnification. The conservation of the water vapour permeability of dry material is used as scaling criterion to link the different pore scales. A macroscopic permeability is deduced from the permeabilities calculated at the different levels of magnification. Each level of magnification is modelled using an isotropic nonplanar 2D cross-squared network. The multiscale network simulates the enhancement of water vapour permeability due to capillary condensation, the hysteresis phenomenon between wetting and drying, and the steep increase of moisture permeability at the critical moisture saturation level. The calculated network permeabilities are compared with experimental data for calcium silicate and ceramic brick and a good agreement is observed.     

The reactions of the Criegee intermediate CH3 CHOO in the gas-phase ozonolysis of 2-butene isomers

Ozonolysis of cis- and trans-2-butene isomers were carried out in a 570 l spherical glass vessel in 730 torr synthetic air at 295 ± 3 K. The initial concentrations were 5 to 10 ppmv for the isomers and 2 to 5 ppmv for ozone. Quantitative yields were determined by FTIR spectroscopy for CH₃CHO, HCHO, CH₄, CH₃OH, CO, and CO₂. By means of computational subtraction of the spectral contribution of the identified products from the product spectra, residual spectra have been obtained. Formation of 2-butene ozonide, propene ozonide, and l-hydroperoxyethyl formate CH₃CH(OOH)(SINGLE BOND)O(SINGLE BOND)CH(O) have been identified in the residual spectra. These products have been shown to be formed in the reactions of the Criegee intermediate CH₃CHOO with CH₃CHO, HCHO, and HCOOH, respectively. Mechanistic implications and atmospheric relevance of these observations are discussed. © 1997 John Wiley & Sons, Inc. Int J Chem Kinet 29: 461–468, 1997.     

Liposome fusion with orthogonal coiled coil peptides as fusogens: the efficacy of roleplaying peptides

Biological membrane fusion is a highly specific and coordinated process as a multitude of vesicular fusion events proceed simultaneously in a complex environment with minimal off-target delivery. In this study, we develop a liposomal fusion model system with specific recognition using lipidated derivatives of a set of four de novo designed heterodimeric coiled coil (CC) peptide pairs. Content mixing was only obtained between liposomes functionalized with complementary peptides, demonstrating both fusogenic activity of CC peptides and the specificity of this model system. The diverse peptide fusogens revealed important relationships between the fusogenic efficacy and the peptide characteristics. The fusion efficiency increased from 20% to 70% as affinity between complementary peptides decreased, (from K_F ≈ 10⁸ to 10⁴ M⁻¹), and fusion efficiency also increased due to more pronounced asymmetric role-playing of membrane interacting ‘K’ peptides and homodimer-forming ‘E’ peptides. Furthermore, a new and highly fusogenic CC pair (E₃/P1_K) was discovered, providing an orthogonal peptide triad with the fusogenic CC pairs P2_E/P2_K and P3_E/P3_K. This E₃/P1_k pair was revealed, via molecular dynamics simulations, to have a shifted heptad repeat that can accommodate mismatched asparagine residues. These results will have broad implications not only for the fundamental understanding of CC design and how asparagine residues can be accommodated within the hydrophobic core, but also for drug delivery systems by revealing the necessary interplay of efficient peptide fusogens and enabling the targeted delivery of different carrier vesicles at various peptide-functionalized locations.

We developed a liposomal fusion model system with specific recognition using a set of heterodimeric coiled coil peptide pairs. This study unravels important structure–fusogenic efficacy relationships of peptide fusogens.     

Polycapillary‐optics‐based micro‐XANES and micro‐EXAFS at a third‐generation bending‐magnet beamline

A focusing system based on a polycapillary half‐lens optic has been successfully tested for transmission and fluorescence µ‐X‐ray absorption spectroscopy at a third‐generation bending‐magnet beamline equipped with a non‐fixed‐exit Si(111) monochromator. The vertical positional variations of the X‐ray beam owing to the use of a non‐fixed‐exit monochromator were shown to pose only a limited problem by using the polycapillary optic. The expected height variation for an EXAFS scan around the Fe K‐edge is approximately 200 µm on the lens input side and this was reduced to ～1 µm for the focused beam. Beam sizes (FWHM) of 12–16 µm, transmission efficiencies of 25–45% and intensity gain factors, compared with the non‐focused beam, of about 2000 were obtained in the 7–14 keV energy range for an incoming beam of 0.5 × 2 mm (vertical × horizontal). As a practical application, an As K‐edge µ‐XANES study of cucumber root and hypocotyl was performed to determine the As oxidation state in the different plant parts and to identify a possible metabolic conversion by the plant.