Discrete approximations for complex Kac–Moody groups

We construct a map from the classifying space of a discrete Kac–Moody group over the algebraic closure of the field with p elements to the classifying space of a complex topological Kac–Moody group and prove that it is a homology equivalence at primes q different from p. This generalizes a classical result of Quillen, Friedlander and Mislin for Lie groups. As an application, we construct unstable Adams operations for general Kac–Moody groups compatible with the Frobenius homomorphism. Our results rely on new integral homology decompositions for certain infinite dimensional unipotent subgroups of discrete Kac–Moody groups.     

Operational risk: Emerging markets,sectors and measurement

The role of decision support systems in mitigating operational risks in firms is well established. However, there is a lack of investment in decision support systems in emerging markets, even though inadequate operational risk management is a key cause of discouraging external investment. This has also been exacerbated by insufficient understanding of operational risk in emerging markets, which can be attributed to past operational risk measurement techniques, limited studies on emerging markets and inadequate data.     

Super‐fast oil uptake using porous ultra‐high molecular weight polyethylene sheets

This paper presents the oil uptake of porous sorbent polymer sheets consisting of ultra‐high molecular weight polyethylene. A comprehensive set of experiments are performed showing the saturation contact time, retention value, mechanical properties, oil pick‐up ratio, pick‐up density, and dynamic dripping profile. Kinetic modeling of the oil sorption is also provided. The experimental results show a good correlation with the pseudo‐second order model. The sheets exhibit high oil uptake speeds, requiring less than 2 min in contact with the oil to reach saturation. The sheets fulfill the criteria of high uptake kinetics, high sorption capacity, and high mechanical strength simultaneously. Those characteristics enable their use in practical spill response. Copyright © 2014 John Wiley & Sons, Ltd.     

Measuring Positive Cooperativity Using the Direct ESI-MS Assay. Cholera Toxin B Subunit Homopentamer Binding to GM1 Pentasaccharide

Direct electrospray ionization mass spectrometry (ESI-MS) assay was used to investigate the stepwise binding of the GM1 pentasaccharide β-D-Galp-(1→3)-β-D-GalpNAc-(1→4)[α-D-Neu5Ac-(2→3)]-β-D-Galp-(1→4)-β-D-Glcp (GM1os) to the cholera toxin B subunit homopentamer (CTB₅) and to establish conclusively whether GM1os binding is cooperative. Apparent association constants were measured for the stepwise addition of one to five GM1os to CTB₅ at pH 6.9 and 22 °C. The intrinsic association constant, which was established from the apparent association constant for the addition of a single GM1os to CTB₅, was found to be (3.2 ± 0.2) × 10⁶ M^–1. This is in reasonable agreement with the reported value of (6.4 ± 0.3) × 10⁶ M^–1, which was measured at pH 7.4 and 25 °C using isothermal titration calorimetry (ITC). Analysis of the apparent association constants provides direct and unambiguous evidence that GM1os binding exhibits small positive cooperativity. Binding was found to be sensitive to the number of ligand-bound nearest neighbor subunits, with the affinities enhanced by a factor of 1.7 and 2.9 when binding occurs next to one or two ligand-bound subunits, respectively. These findings, which provide quantitative support for the binding model proposed by Homans and coworkers [14], highlight the unique strengths of the direct ESI-MS assay for measuring cooperative ligand binding.

Screening Carbohydrate Libraries for Protein Interactions Using the Direct ESI-MS Assay. Applications to Libraries of Unknown Concentration

A semiquantitative electrospray ionization mass spectrometry (ESI-MS) binding assay suitable for analyzing mixtures of oligosaccharides, at unknown concentrations, for interactions with target proteins is described. The assay relies on the differences in the ratio of the relative abundances of the ligand-bound and free protein ions measured by ESI-MS at two or more initial protein concentrations to distinguish low affinity (≤10³ M^–1) ligands from moderate and high affinity (>10⁵ M^–1) ligands present in the library and to rank their affinities. Control experiments were performed on solutions of a single chain antibody and a mixture of synthetic oligosaccharides, with known affinities, in the absence and presence of a 40-component carbohydrate library to demonstrate the implementation and reliability of the assay. The application of the assay for screening natural libraries of carbohydrates against proteins is also demonstrated using mixtures of human milk oligosaccharides, isolated from breast milk, and fragments of a bacterial toxin and human galectin 3. Graphical Abstract

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Mass Spectral Peak Distortion Due to Fourier Transform Signal Processing

Distortions of peaks can occur when one uses the standard method of signal processing of data from the Orbitrap and other FT-based methods of mass spectrometry. These distortions arise because the standard method of signal processing is not a linear process. If one adds two or more functions, such as time-dependent signals from a Fourier transform mass spectrometer and performs a linear operation on the sum, the result is the same as if the operation was performed on separate functions and the results added. If this relationship is not valid, the operation is non-linear and can produce unexpected and/or distorted results. Although the Fourier transform itself is a linear operator, the standard algorithm for processing spectra in Fourier transform-based methods include non-linear mathematical operators such that spectra processed by the standard algorithm may become distorted. The most serious consequence is that apparent abundances of the peaks in the spectrum may be incorrect. In light of these considerations, we performed theoretical modeling studies to illustrate several distortion effects that can be observed, including abundance distortions. In addition, we discuss experimental systems where these effects may manifest, including suggested systems for study that should demonstrate these peak distortions. Finally, we point to several examples in the literature where peak distortions may be rationalized by the phenomena presented here. Graphical Abstract

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The development and assessment of high‐throughput mass spectrometry‐based methods for the quantification of a nanoparticle drug delivery agent in cellular lysate

The safe use of lipid‐based drug delivery agents requires fast and sensitive qualitative and quantitative assessment of their cellular interactions. Many mass spectrometry (MS) based analytical platforms can achieve such task with varying capabilities. Therefore, four novel high‐throughput MS‐based quantitative methods were evaluated for the analysis of a small organic gene delivery agent: N,N‐bis(dimethylhexadecyl)‐1,3‐propane‐diammonium dibromide (G16‐3). Analysis utilized MS instruments that detect analytes using low‐resolution tandem MS (MS/MS) analysis (i.e. QTRAP or linear ion trap in this work) or high‐resolution MS analysis (i.e. time of flight (ToF) or Orbitrap). Our results indicate that the validated fast chromatography (FC)‐QTRAP‐MS/MS, FC‐ LTQ‐Orbitrap‐MS, desorption electrospray ionization‐collision‐induced dissociation (CID)‐MS/MS and matrix assisted laser desorption ionization‐ToF/ToF‐MS MS methods were superior in the area of method development and sample analysis time to a previously developed liquid chromatography (LC)‐CID‐MS/MS. To our knowledge, this is the first evaluation of the abilities of five MS‐based quantitative methods that target a single pharmaceutical analyte. Our findings indicate that, in comparison to conventional LC‐CID‐MS/MS, the new MS‐based methods resulted in a (1) substantial reduction in the analysis time, (2) reduction in the time required for method development and (3) production of either superior or comparable quantitative data. The four new high‐throughput MS methods, therefore, were faster, more efficient and less expensive than a conventional LC‐CID‐MS/MS for the quantification of the G16‐3 analyte within tissue culture. When applied to cellular lysate, no significant change in the concentration of G16‐3 gemini surfactant within PAM212 cells was observed between 5 and 53 h, suggesting the absence of any metabolism/excretion from PAM212 cells. Copyright © 2014 John Wiley & Sons, Ltd.     

Mild Bioconjugation Through the Oxidative Coupling of ortho‐Aminophenols and Anilines with Ferricyanide

Using a small‐molecule‐based screen, ferricyanide was identified as a mild and efficient oxidant for the coupling of anilines and o‐aminophenols on protein substrates. This reaction is compatible with thiols and 1,2‐diols, allowing its use in the creation of complex bioconjugates for use in biotechnology and materials applications.     

Picolinamides as Effective Ligands for Copper‐Catalysed Aryl Ether Formation: Structure–Activity Relationships,Substrate Scope and Mechanistic Investigations

The use of picolinic acid amide derivatives as an effective family of bidentate ligands for copper‐catalysed aryl ether synthesis is reported. A fluorine‐substituted ligand gave good results in the synthesis of a wide range of aryl ethers. Even bulky phenols, known to be very challenging substrates, were shown to react with aryl iodides with excellent yields using these ligands. At the end of the reaction, the first examples of end‐of‐life Cu species were isolated and identified as Cu^II complexes with several of the anionic ligands tested. A preliminary mechanistic investigation is reported that suggests that the substituents on the ligands might have a crucial role in determining the redox properties of the metal centre and, consequently, its efficacy in the coupling process. An understanding of these effects is important for the development of new efficient and tunable ligands for copper‐based chemistry.