On the formulation of thermodynamically-consistent viscoplastic-damage constitutive models.

This paper illustrates the formulation of viscoplastic-damage constitutive models using the framework of hyperplasticity. The entire constitutive behaviour is derived from only two scalar potentials; a free energy potential and a dissipation potential. This ensures that the model obeys the laws of thermodynamics

A Monitor of Beam Polarization Profiles for the TRIUMF Parity Experiment

TRIUMF experiment E497 is a study of parity violation in pp scattering at an energy where the leading term in the analyzing power is expected to vanish, thus measuring a unique combination of weak-interaction flavour conserving terms. It is desired to reach a level of sensitivity of 2x10^-8 in both statistical and systematic errors. The leading systematic errors depend on transverse polarization components and, at least, the first moment of transverse polarization. A novel polarimeter that measures profiles of both transverse components of polarization as a function of position is described.Comment: 19 pages LaTeX, 10 PostScript figures. To appear in Nuclear Instruments and Methods in Physics Research, Section

GMP compliant isolation of mucosal epithelial cells and fibroblasts from biopsy samples for clinical tissue engineering

Engineered epithelial cell sheets for clinical replacement of non-functional upper aerodigestive tract mucosa are regulated as medicinal products and should be manufactured to the standards of good manufacturing practice (GMP). The current gold standard for growth of epithelial cells for research utilises growth arrested murine 3T3 J2 feeder layers, which are not available for use as a GMP compliant raw material. Using porcine mucosal tissue, we demonstrate a new method for obtaining and growing non-keratinised squamous epithelial cells and fibroblast cells from a single biopsy, replacing the 3T3 J2 with a growth arrested primary fibroblast feeder layer and using pooled Human Platelet lysate (HPL) as the media serum supplement to replace foetal bovine serum (FBS). The initial isolation of the cells was semi-automated using an Octodissociator and the resultant cell suspension cryopreservation for future use. When compared to the gold standard of 3T3 J2 and FBS containing medium there was no reduction in growth, viability, stem cell population or ability to differentiate to mature epithelial cells. Furthermore, this method was replicated with Human buccal tissue, providing cells of sufficient quality and number to create a tissue engineered sheet

Novel HSPB1 mutation causes both motor neuronopathy and distal myopathy.

OBJECTIVE: To identify the cause of isolated distal weakness in a family with both neuropathic and myopathic features on EMG and muscle histology. METHODS: Case study with exome sequencing in 2 affected individuals, bioinformatic prioritization of genetic variants, and segregation analysis of the likely causal mutation. Functional studies included Western blot analysis of the candidate protein before and after heat shock treatment of primary skin fibroblasts. RESULTS: A novel HSPB1 variant (c.387C>G, p.Asp129Glu) segregated with the phenotype and was predicted to alter the conserved α-crystallin domain common to small heat shock proteins. At baseline, there was no difference in HSPB1 protein levels nor its binding partner αB-crystallin. Heat shock treatment increased HSPB1 protein levels in both patient-derived and control fibroblasts, but the associated increase in αB-crystallin expression was greater in patient-derived than control fibroblasts. CONCLUSIONS: The HSPB1 variant (c.387C>G, p.Asp129Glu) is the likely cause of distal neuromyopathy in this pedigree with pathogenic effects mediated through binding to its partner heat shock protein αB-crystallin. Mutations in HSBP1 classically cause a motor axonopathy, but this family shows that the distal weakness can be both myopathic and neuropathic. The traditional clinical classification of distal weakness into "myopathic" or "neuropathic" forms may be misleading in some instances, and future treatments need to address the pathology in both tissues.This study was funded by Wellcome Trust (101876/Z/13/Z and 096919Z/11/Z), Medical Research Council (UK) (G0601943), and Medical Research Council Mitochondrial Biology Unit (MC_UP_1501/2). Funding bodies had no influence on study design or data interpretation.This is the final version of the article. It first appeared from Wolters Kluwer via http://dx.doi.org/10.1212/NXG.000000000000011

Supramolecular Tuning of Spin Crossover Properties in Isostructural Cocrystal Solvates

In order to improve strategies for the design of spin-crossover materials, it is necessary to develop and understand structure–property relationships, and this is best achieved by obtaining isostructural materials. In this work we synthesized a series of four isostructural cocrystal solvates using the [Fe­(3-bpp)2]­[A]2 complex and the 2,2-dipyridyl disulfide coformer in methanol and ethanol (A = BF4 – or PF6 –). The spin-crossover properties of the materials were determined by variable temperature single-crystal X-ray diffraction. They show the same SCO behavior but with shifted spin-crossover temperatures, which has been related to the hydrogen bond basicity, pK BHX of the anions, and solvents present. This relationship between hydrogen bond basicity and the spin-crossover transition temperature offers a design strategy for the supramolecular tuning of spin-crossover properties in specific isostructural materials

Co-crystallisation as a modular approach to the discovery of spin-crossover materials

Herein we present co-crystallisation as a strategy for materials discovery in the field of switchable spin crossover (SCO) systems. Using [Fe(3-bpp)2]·2A (where 3-bpp = 2,6-bis(pyrazol-3-yl)pyridine, A = BF4−/PF6−) as a starting point, a total of 11 new cocrystals have been synthesised with five different dipyridyl coformers. Eight of these systems show spin crossover behaviour, and all show dramatically different switching properties from the parent complex. The cocrystals have been studied by variable temperature single-crystal X-ray diffraction and SQUID magnetometry to develop structure–property relationships. The supramolecular architecture of the cocrystals depends on the properties of the coformer. With linear, rigid coformer molecules leading to 1D supramolecular hydrogen-bonded chains, while flexible coformers form 2D sheets and bent coformers yield 3D network structures. The SCO behaviour of the cocrystals can be modified through changing the coformer and thus co-crystallisation presents a rapid, facile and highly modular tool for the discovery of new switchable materials. The wider applicability of this strategy to the design of hybrid multifunctional materials is also discussed

Angular distributions of protons scattered by 40 Ar nuclei with excitation of the 2 + (1.46 MeV) and 3 − (3.68 MeV) collective levels for incident energies of 25.1, 32.5, and 40.7 MeV

Elastic and inelastic scattering of unpolarized and polarized protons by 40Ar nuclei for incident energies between 20 and 50 MeV has been studied by reanalyzing experimental scattering spectra for the 2+(1.46 MeV) and 3-(3.68 MeV) levels in the angular range 30º–160º for incident protons of energies of 25.1, 32.5, and 40.7 MeV. An isospin dependent soft-rotator coupled-channels optical model with the potential containing a dispersive term with a nonlocal contribution is used to analyze the data

Natural mutations of human XDH promote the nitrite (NO2 −)-reductase capacity of xanthine oxidoreductase: A novel mechanism to promote redox health?

Several rare genetic variations of human XDH have been shown to alter xanthine oxidoreductase (XOR) activity leading to impaired purine catabolism. However, XOR is a multi-functional enzyme that depending upon the environmental conditions also expresses oxidase activity leading to both O2·- and H2O2 and nitrite (NO2−) reductase activity leading to nitric oxide (·NO). Since these products express important, and often diametrically opposite, biological activity, consideration of the impact of XOR mutations in the context of each aspect of the biochemical activity of the enzyme is needed to determine the potential full impact of these variants. Herein, we show that known naturally occurring hXDH mutations do not have a uniform impact upon the biochemical activity of the enzyme in terms of uric acid (UA), reactive oxygen species (ROS) and nitric oxide ·NO formation. We show that the His1221Arg mutant, in the presence of xanthine, increases UA, O2·- and NO generation compared to the WT, whilst the Ile703Val increases UA and ·NO formation, but not O2·-. We speculate that this change in the balance of activity of the enzyme is likely to endow those carrying these mutations with a harmful or protective influence over health that may explain the current equipoise underlying the perceived importance of XDH mutations. We also show that, in presence of inorganic NO2−, XOR-driven O2·- production is substantially reduced. We suggest that targeting enzyme activity to enhance the NO2−-reductase profile in those carrying such mutations may provide novel therapeutic options, particularly in cardiovascular disease