Effect of helium/neon laser irradiation on nerve growth factor synthesis and secretion in skeletal muscle cultures

Low energy laser irradiation therapy in medicine is widespread but the mechanisms are not fully understood. The aim of the present study was to elucidate the mechanism by which the light might induce therapeutic effects. Skeletal muscle cultures were chosen as a target for light irradiation and nerve growth factor (NGF) was the biochemical marker for analysis. It was found that there is a transient elevation of intracellular calcium in the myotubes immediately after irradiation (P<0.001). Preincubation of the myotubes with either the photosensitizers 5-amino-levulinic acid (5-ALA), or with hematoporphyrin (Hp) enhanced the elevation of cytosolic calcium (P<0.001) after helium/neon irradiation (633 nm) with an energy of 3 J/cm(2). In addition, helium/neon irradiation augmented the level of NGF mRNA fivefold and increased NGF release to the medium of the myotubes. Thus, it is speculated that transient changes in calcium caused by light can modulate NGF release from the myotubes and also affect the nerves innervating the muscle. The NGF is probably responsible for the beneficial effects of low-level light.     

Identification of Two Distinct Sites for Antagonist and Biased Agonist Binding to the Human Chemokine Receptor CXCR3

The chemokine receptor CXCR3 is a G protein‐coupled receptor that conveys extracellular signals into cells by changing its conformation upon ligand binding. We previously hypothesized that small‐molecule allosteric CXCR3‐agonists do not bind to the same allosteric binding pocket as 8‐azaquinazolinone‐based negative allosteric modulators. We have now performed molecular‐dynamics (MD) simulations with metadynamics enhanced sampling on the CXCR3 system to refine structures and binding modes and to predict the CXCR3‐binding affinities of the biased allosteric agonist FAUC1036 and the negative allosteric modulator RAMX3. We have identified two distinct binding sites; a “shallow” and a second “deeper” pocket to which the biased allosteric agonist FAUC1036 and negative allosteric modulator RAMX3 bind, respectively.     

Three-dimensional finite element modeling of guided ultrasound wave propagation in intact and healing long bones

The use of guided waves has recently drawn significant interest in the ultrasonic characterization of bone aiming at supplementing the information provided by traditional velocity measurements. This work presents a three-dimensional finite element study of guided wave propagation in intact and healing bones. A model of the fracture callus was constructed and the healing course was simulated as a three-stage process. The dispersion of guided modes generated by a broadband 1-MHz excitation was represented in the time-frequency domain. Wave propagation in the intact bone model was first investigated and comparisons were then made with a simplified geometry using analytical dispersion curves of the tube modes. Then, the effect of callus consolidation on the propagation characteristics was examined. It was shown that the dispersion of guided waves was significantly influenced by the irregularity and anisotropy of the bone. Also, guided waves were sensitive to material and geometrical changes that take place during healing. Conversely, when the first-arriving signal at the receiver corresponded to a nondispersive lateral wave, its propagation velocity was almost unaffected by the elastic symmetry and geometry of the bone and also could not characterize the callus tissue throughout its thickness. In conclusion, guided waves can enhance the capabilities of ultrasonic evaluation.     

A rate equation method for the sequential double ionisation, including autoionising state excitation, of a noble gas

A set of rate equations have been tested against a more robust set of Time-Dependent Density Matrix (TDDM) equations [D. P. W. Middleton, L. A. A. Nikolopoulos, J. Mod. Opti. 59, 1650 (2012)] by using them to determine the populations of ion species and autoionising states (AIS) in noble gas atoms when interacting with a strong external field. Two field shapes were tested here — sinusoidal and square — and a variety of pulse characteristics were examined, i.e. intensity, duration and photon energy, for the neon atomic system. It was found that the rate equations were sufficiently accurate only when the external field is way off-resonant with the AIS. Moreover, analytical solutions of the rate equations in the square pulse case agree with the numerical solutions for a time-dependent pulse containing many cycles. An attempt to model a stochastic field was also made and it was found that the use of such a field diminished and broadened the ion yield ratio due to the presence of an added bandwidth.     

Causal study of low stakeholder engagement in healthcare simulation projects

Stakeholder engagement plays a fundamental role in the success of ‘operational research’ initiatives including simulation projects. However, there is little empirical evidence of real engagement in the context of healthcare simulation. This paper principally examines this issue and aims to provide insights into the possible causes. The paper reports on the results of a literature review and 10 field studies within the UK healthcare settings, supplemented with the authors’ experience in order to arrive at an initial list of the causes, which will then be tested through a survey of expert opinions. Twelve primary and 26 secondary causal factors, which received statistically significant level of agreement from the experts, are presented in a fish-bone diagram. The findings indicate that communication gap between simulation and stakeholder groups is the top primary factor contributing the most to the poor stakeholder engagement in healthcare simulation projects, followed by ‘poor management support’, ‘clinician’s high workload’ and ‘failure in producing tangible and quick results’.     

Amidoglycosylation via metal-catalyzed internal nitrogen atom delivery

[reaction: see text] Rhodium and copper acyl nitrenoids are likely intermediates in amidoglycosylation reactions of allal 3-carbamates. Iodine(III)-mediated nitrenoid formation, interaction of this species with the glycal enol ether pi-system, and highly beta-stereoselective glycosylation occur in a one-pot process that requires no additional Lewis acid activation.     

Magnetic susceptibilities and knight shifts of the intermetallic compounds NdCu4 and NdCu5

The magnetic susceptibility and Knight shift of the intermetallic compounds NdCu₄ and NdCu₅ were investigated over the temperature range 80–850 K. The most important contributions to the magnetic susceptibility are the Curie-Weiss term, expressing the paramagnetism of the localized 4?-electrons, and a temperature independent term, both of which have been determined. The phenomenological quantity J_s? between the 4?-electron and conduction electron spins was found to be ?2.46.10^?3eV for NdCu₄ and 1.35.10^?3 eV for NdCu₅. A reversal in the sign of the s-? coupling for CeCu₅ was noted.