Non-invasive in vivo imaging in small animal research

Non-invasive real time in vivo molecular imaging in small animal models has become the essential bridge between in vitro data and their translation into clinical applications. The tremendous development and technological progress, such as tumour modelling, monitoring of tumour growth and detection of metastasis, has facilitated translational drug development. This has added to our knowledge on carcinogenesis. The modalities that are commonly used include Magnetic Resonance Imaging (MRI), Computed Tomography (CT), Positron Emission Tomography (PET), bioluminescence imaging, fluorescence imaging and multi-modality imaging systems. The ability to obtain multiple images longitudinally provides reliable information whilst reducing animal numbers. As yet there is no one modality that is ideal for all experimental studies. This review outlines the instrumentation available together with corresponding applications reported in the literature with particular emphasis on cancer research. Advantages and limitations to current imaging technology are discussed and the issues concerning small animal care during imaging are highlighted.

A multi-fibre multi-layer representative volume element (M2RVE) for prediction of matrix and interfacial damage in composite laminates

Multiscale micro-mechanics theory is extensively used for the prediction of the material response and damage analysis of unidirectional lamina using a representative volume element (RVE). Th is paper presents a RVE-based approach to characterize the materi al response of a multi-fibre cross-ply laminate considering the effect of matrix damage and fibre-matrix interfacial strength. The framework of the homogenization theory for periodic media has been used for the analysis of a 'multi-fibre multi-layer representative volume element' (M2 RVE) representing cross-ply laminate. The non-homogeneous stress-strain fields within the M2RVE are related to the average stresses and strains by using Gauss theorem and the Hill-Mandal strain energy equivalence principle. The interfacial bonding strength affects the in-plane shear stress-strain response significantl y. The material response predicted by M2 RVE is in good agreement with the experimental results available in the literature. The maximum difference between the shear stress predicted using M2 RVE and the experimental results is ~15% for the bonding strength of 30MPa at the strain value of 1.1%

An efficient harmony search with new pitch adjustment for dynamic economic dispatch

A simple yet efficient harmony search (HS) method with a new pitch adjustment rule (NPAHS) is proposed for dynamic economic dispatch (DED) of electrical power systems, a large-scale non-linear real time optimization problem imposed by a number of complex constraints. The new pitch adjustment rule is based on the perturbation information and the mean value of the harmony memory, which is simple to implement and helps to enhance solution quality and convergence speed. A new constraint handling technique is also developed to effectively handle various constraints in the DED problem, and the violation of ramp rate limits between the first and last scheduling intervals that is often ignored by existing approaches for DED problems is effectively eliminated. To validate the effectiveness, the NPAHS is first tested on 10 popular benchmark functions with 100 dimensions, in comparison with four HS variants and five state-of-the-art evolutionary algorithms. Then, NPAHS is used to solve three 24-h DED systems with 5, 15 and 54 units, which consider the valve point effects, transmission loss, emission and prohibited operating zones. Simulation results on all these systems show the scalability and superiority of the proposed NPAHS on various large scale problems.

Quantum manifestations of scattering orbits in the scaled spectrum of a non-hydrogenic atom in crossed fields

Evidence for scattering closed orbits for the Rydberg electron of the singly excited helium atom in crossed electric and magnetic fields at constant scaled energy and constant scaled electric field strength has been found through a quantum calculation of the photo-excitation spectrum. A particular 3D scattering orbit in a mixed regular and chaotic region has been investigated and the hydrogenic 3D closed orbits composing it identified. To the best of our knowledge, this letter reports the first quantum calculation of the scaled spectrum of a non- hydrogenic atom in crossed fields.

Quantum manifestations of closed orbits in the photoexcitation scaled spectrum of the hydrogen atom in crossed fields

The scaled photoexcitation spectrum of the hydrogen atom in crossed electric and magnetic fields has been obtained by means of accurate quantum mechanical calculation using a new algorithm. Closed orbits in the corresponding classical system have also been obtained, using a new, efficient and practical searching procedure. Two new classes of closed orbit have been identified. Fourier transforming each photoexcitation quantum spectrum to yield a plot against scaled action has allowed direct comparison between peaks in such plots and the scaled action values of closed orbits, Excellent agreement has been found with all peaks assigned.

The closed orbits and the photo-excitation scaled spectrum of the hydrogen atom in crossed fields

In a recent Letter to the Editor (J Rao, D Delande and K T Taylor 2001 J. Phys. B: At. Mol. Opt. Phys. 34 L391-9) we made a brief first report of our quantal and classical calculations for the hydrogen atom in crossed electric and magnetic fields at constant scaled energy and constant scaled electric field strength. A principal point of that communication was our statement that each and every peak in the Fourier transform of the scaled quantum photo-excitation spectrum for scaled energy value epsilon = -0.586 538 871028 43 and scaled electric value (f) over tilde = 0.068 537 846 207 618 71 could be identified with a scaled action value of a found and mapped-out closed orbit up to a scaled action of 20. In this follow-up paper, besides presenting full details of our quantum and classical methods, we set out the scaled action values of all 317 closed orbits involved, together with the geometries of many.

Progressive loss of ferroelectricity under bipolar pulsed fields and experimental determination of non-switchable polarization in Au/Ba0.5Sr0.5TiO3/SrRuO3 thin-film capacitors

175 nm-thick Ba0.5Sr0.5TiO3 (BST) thin film fabricated by pulsed laser deposition (PLD) technique is found to be a mixture of two distributions of material. We discuss whether these two components are nano-regions of paraelectric and ferroelectric phases, or a bimodal grain-size distribution, or an effect of oxygen vacancy gradient from the electrode interface. The fraction of switchable ferroelectric phase decreases under bipolar pulsed fields, but it recovers after removal of the external fields. The plot of capacitance in decreasing dc voltage (C(Vdown arrow) versus that in increasing dc 61 voltage C(Vup arrow) is a superposition of overlapping of two triangles, in contrast to one well-defined triangle for typical ferroelectric SrBi2Ta2O9 thin films.

An infinite-dimensional separable pre-Hilbert space non-homeomorphic to any of its closed hyperplanes

An example is constructed of an infinite-dimensional separable pre-Hilbert space non-homeomorphic to any of its closed hyperplanes.

Sequential versus non-sequential double ionization in strong laser fields

<p> The recollision model has been applied to separate the probability for double ionization into contributions from electron-impact ionization and electron-impact excitation for intensities at which the dielectronic interaction is important for generating double ionization. For a wavelength of 780 am, electron-impact excitation dominates just above the threshold intensity for double ionization, approximate to 1.2 x 10(14) W cm(-2), with electron-impact ionization becoming more important for higher intensities. For a wavelength of 390 nm, the ratio between electron-impact ionization and electron-impact excitation remains fairly constant for all intensities above the threshold intensity for double ionization, approximate to 6 x 10(14) W cm(-2). The results point to an explanation of the experimental results, but more detailed calculations on the behaviour of excited He+ ions are required.</p>

Dose, dose-rate and field size effects on cell survival following exposure to non-uniform radiation fields

For the delivery of intensity-modulated radiation therapy (IMRT), highly modulated fields are used to achieve dose conformity across a target tumour volume. Recent in vitro evidence has demonstrated significant alterations in cell survival occurring out-of-field which cannot be accounted for on the basis of scattered dose. The radiobiological effect of area, dose and dose-rate on out-of-field cell survival responses following exposure to intensity-modulated radiation fields is presented in this study. Cell survival was determined by clonogenic assay in human prostate cancer (DU-145) and primary fibroblast (AG0-1522) cells following exposure to different modulated field configurations delivered using a X-Rad 225 kVp x-ray source. Uniform survival responses were compared to in- and out-of-field responses in which 25-99% of the cell population was shielded. Dose delivered to the out-of-field region was varied from 1.6-37.2% of that delivered to the in-field region using different levels of brass shielding. Dose rate effects were determined for 0.2-4 Gy min⁻¹ for uniform and modulated exposures with no effect seen in- or out-of-field. Survival responses showed little dependence on dose rate and area in- and out-of-field with a trend towards increased survival with decreased in-field area. Out-of-field survival responses were shown to scale in proportion to dose delivered to the in-field region and also local dose delivered out-of-field. Mathematical modelling of these findings has shown survival response to be highly dependent on dose delivered in- and out-of-field but not on area or dose rate. These data provide further insight into the radiobiological parameters impacting on cell survival following exposure to modulated irradiation fields highlighting the need for refinement of existing radiobiological models to incorporate non-targeted effects and modulated dose distributions.

Quantum and classical properties of the fields generated by two interlinked second-order non-linear interactions

We consider two interlinked non-linear interactions occurring simultaneously in a single chi((2)) crystal. Classical and quantum working regimes are considered and their peculiar properties analysed. In particular, we describe an experiment, realized in the classical regime, that verifies the holographic nature of the process, and predict, for the quantum regime, the generation of a fully inseparable tripartite Gaussian state of light that can be used to support a general 1--> 2 continuous variable telecloning protocol.

Conventional in vivo irradiation procedures are insufficient to accurately determine tumor responses to non-uniform radiation fields

Purpose: To determine differences in overall tumor responses measured by volumetric assessment and bioluminescence imaging (BLI) following exposure to uniform and non-uniform radiation fields in an ectopic prostate tumor model.

Materials and methods: Bioluminescent human prostate tumor xenografts were established by subcutaneous implantation into male mice. Tumors were irradiated with uniform or non-uniform field configurations using conventional in vivo irradiation procedures performed using a 225 kVp generator with custom lead shielding. Tumor responses were measured using Vernier calipers and by BLI using an in vivo imaging system. Survival was defined as the time to quadroupling of pre-treatment tumor volume. 

Results: The correlation between BLI and tumor volume measurements was found to be different for un-irradiated (R = 0.61), uniformly irradiated (R = 0.34) and partially irradiated (R = 0.30) tumors. Uniformly irradiated tumors resulted in an average tumor growth delay of 60 days with median survival of 75 days, compared to partially irradiated tumors which showed an average growth delay of 24 days and median survival of 38 days. 

Conclusions: Correlation between BLI and tumor volume measurements is lower for partially irradiated tumors than those exposed to uniform dose distributions. The response of partially irradiated tumors suggests non-uniformity in response beyond physical dose distribution within the target volume. Dosimetric uncertainty associated with conventional in vivo irradiation procedures prohibits their ability to accurately determine tumor response to non-uniform radiation fields and stresses the need for image guided small animal radiation research platforms.