Synthesis and Systematic Study on the Effect of Different PEG Units on Stability of PEGylated,Integrin-αvβ6-Specific A20FMDV2 Analogues in Rat Serum and Human Plasma

A20FMDV2 is a 20-mer peptide that exhibits high selectivity and affinity for the tumour-related αvβ6 integrin that can compete with extracellular ligands for the crucial RGD binding site, playing a role as a promising αvβ6-specific inhibitor for anti-cancer therapies. Unfortunately, the clinical value of A20FMDV2 is limited by its poor half-life in blood caused by rapid renal excretion and its reported high susceptibility to serum proteases. The incorporation of poly (ethylene glycol) chains, coined PEGylation, is a well-established approach to improve the pharmacokinetic properties of drug molecules. Here, we report a systematic study on the incorporation of a varying number of ethylene glycol units (1–20) into the A20FMDV2 peptide to establish the effects of PEGylation size on the peptide stability in both rat serum and human plasma. In addition, the effect of acetyl and propionyl PEGylation handles on peptide stability is also described. Selected peptide analogues were assessed for integrin-αvβ6-targeted binding, showing good specificity and activity in vitro. Stability studies in rat serum established that all of the PEGylated peptides displayed good stability, and an A20FMDV2 peptide containing twenty ethylene glycol units (PEG₂₀) was the most stable. Surprisingly, the stability testing in human plasma identified shorter PEGs (PEG₂ and PEG₅) as more resistant to degradation than longer PEGs, a trend which was also observed with affinity binding to integrin αvβ6.     

Role of structure in amorphous magnetic materials: Dense random packing of hard spheres of two sizes

We investigate the structure of amorphous rare-earth transition-metal alloys and its influence on their magnetic properties in the context of a simple model. The packing fraction of the alloys is discussed using both ball-bearing assemblies and also computer-generated clusters of randomly close-packed hard spheres, and the latter clusters are used to discuss the radial distribution functions (RDF's) and the magnetic anisotropy. The computer-generated RDF's are compared with published neutron diffraction results on amorphous TbFe₂.     

A structure determination protocol based on combined analysis of 3D-ED data,powder XRD data,solid-state NMR data and DFT-D calculations reveals the structure of a new polymorph of l-tyrosine

We report the crystal structure of a new polymorph of l-tyrosine (denoted the β polymorph), prepared by crystallization from the gas phase following vacuum sublimation. Structure determination was carried out by combined analysis of three-dimensional electron diffraction (3D-ED) data and powder X-ray diffraction (XRD) data. Specifically, 3D-ED data were required for reliable unit cell determination and space group assignment, with structure solution carried out independently from both 3D-ED data and powder XRD data, using the direct-space strategy for structure solution implemented using a genetic algorithm. Structure refinement was carried out both from powder XRD data, using the Rietveld profile refinement technique, and from 3D-ED data. The final refined structure was validated both by periodic DFT-D calculations, which confirm that the structure corresponds to an energy minimum on the energy landscape, and by the fact that the values of isotropic ¹³C NMR chemical shifts calculated for the crystal structure using DFT-D methodology are in good agreement with the experimental high-resolution solid-state ¹³C NMR spectrum. Based on DFT-D calculations using the PBE0-MBD method, the β polymorph is meta-stable with respect to the previously reported crystal structure of l-tyrosine (now denoted the α polymorph). Crystal structure prediction calculations using the AIRSS approach suggest that there are three other plausible crystalline polymorphs of l-tyrosine, with higher energy than the α and β polymorphs.

A new polymorph of l-tyrosine is reported, with the crystal structure determined by combined analysis of 3D-ED data and powder XRD data, augmented by information from periodic DFT-D calculations and solid-state ¹³C NMR data.     

Modelling of a novel high-impedance matching layer for high frequency (>30 MHz) ultrasonic transducers

This work describes a new approach to impedance matching for ultrasonic transducers. A single matching layer with high acoustic impedance of 16 MRayls is demonstrated to show a bandwidth of around 70%, compared with conventional single matching layer designs of around 50%. Although as a consequence of this improvement in bandwidth, there is a loss in sensitivity, this is found to be similar to an equivalent double matching layer design. Designs are calculated by using the KLM model and are then verified by FEA simulation, with very good agreement Considering the fabrication difficulties encountered in creating a high-frequency double matched design due to the requirement for materials with specific acoustic impedances, the need to accurately control the thickness of layers, and the relatively narrow bandwidths available for conventional single matched designs, the new approach shows advantages in that alternative (and perhaps more practical) materials become available, and offers a bandwidth close to that of a double layer design with the simplicity of a single layer design. The disadvantage is a trade-off in sensitivity. A typical example of a piezoceramic transducer matched to water can give a 70% fractional bandwidth (comparable to an ideal double matched design of 72%) with a 3 dB penalty in insertion loss.     

Spectroscopic fingerprints of valence and spin states in manganese oxides and fluorides

We performed a systematic study of soft X-ray absorption spectroscopy in various manganese oxides and fluorides. Both Mn L-edges and ligand (O and F) K-edges are presented and compared with each other. Despite the distinct crystal structure and covalent/ionic nature in different systems, the Mn-L spectra fingerprint the Mn valence and spin states through spectral lineshape and energy position consistently and evidently. The clear O- and F-K pre-edge features in our high resolution spectra enable a quantitative definition of the molecular orbital diagram with different Mn valence. In addition, while the binding energy difference of the O-1s core electrons leads to a small shift of the O-K leading edges between trivalent and quadrivalent manganese oxides, a significant edge shift, with an order of magnitude larger in energy, was found between divalent and trivalent compounds, which is attributed to the spin exchange stabilization of half-filled 3d system. This shift is much enhanced in the ionic fluoride system. This work provides the spectroscopic foundation for further studies of complicated Mn compounds.     

Silicon doping of MBE-grown GaAs films

Two concentration ranges of silicon doping in MBE-grown GaAs films have been investigated in some detail. In lightly doped films, with a free-electron concentration of ≈10¹⁶cm^?3, low-temperature photoluminescence spectra have been analysed to develop a model to account for spectral features previously attributed to Ge and Si acceptor levels. In heavily doped films, a maximum free-electron concentration of ≈7×10¹⁸ cm^?3 has been obtained, which is only rather weakly dependent on growth conditions and the nature of the arsenic species (As₂ or As₄). Transmission electron microscopy has shown that no significant precipitation effects occur when higher Si fluxes are used but there is evidence for autocompensation. The maximum PL intensity (300 K) is found at a lower free electron concentration then with Sn-doped films, and is more sharply peaked, but there is no evidence for an anomalous Moss-Burstein shift.     

High-resolution laser excitation spectra of linear triatomic molecules: Analysis of the B2Σ+-X2Σ+ system of SrOH and SrOD

Single-mode cw dye laser excitation spectra of the (0, 0⁰, 0)-(0, 0⁰, 0), (1, 0⁰, 0)-(1, 0⁰, 0), (0, 1¹, 0)-(0, 1¹, 0) bands of the 611- to 607-nm system of SrOH and SrOD were observed and assigned. The spectrum is consistent with a ²Σ-²Σ system where the molecule is linear in both electronic states. The rotational analysis is obtained by measuring P-R separations in the excitation spectrum. A technique which greatly aided in the spectral assignment that utilizes a monochromator as a bandpass filter in obtaining excitation spectra is described. A new spin-rotation constant, γ⁽⁺⁾ - γ^(?), was found necessary to fit the l-type doubling of the (0, 1¹, 0) mode in B²Σ⁺ of SrOH. This new constant is assumed to arise from two ${}^2\text{Σ}{}_{\mathrm{<mtext>1</mtext><mtext>2</mtext>}}$ vibronic states, split by Renner-Teller interaction, of the (0, 1¹, 0) mode of A²Π. From a perturbation treatment of this electronic interaction, ?ω₂ of the (0, 1¹, 0) mode of A²Π was found to be 14 cm^?1. The linear structure of SrOH and SrOD in both electronic states is consistent with the model, in the one-electron approximation, in that the transition involves the promotion of the unpaired 5s to the 5p orbital localized on the strontium.     

Simulations of ferrite-dielectric-wire composite negative index materials

We perform extensive finite difference time domain simulations of ferrite based negative index of refraction composites. A wire grid is employed to provide negative permittivity. The ferrite and wire grid interact to provide both negative and positive index of refraction transmission peaks in the vicinity of the ferrite resonance. Notwithstanding the extreme anisotropy in the index of refraction of the composite, negative refraction is seen at the composite air interface allowing the construction of a focusing concave lens with a magnetically tunable focal length.