2 resultados para Spatially explicit model


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The category of rational SO(2)--equivariant spectra admits an algebraic model. That is, there is an abelian category A(SO(2)) whose derived category is equivalent to the homotopy category of rational$SO(2)--equivariant spectra. An important question is: does this algebraic model capture the smash product of spectra? The category A(SO(2)) is known as Greenlees' standard model, it is an abelian category that has no projective objects and is constructed from modules over a non--Noetherian ring. As a consequence, the standard techniques for constructing a monoidal model structure cannot be applied. In this paper a monoidal model structure on A(SO(2)) is constructed and the derived tensor product on the homotopy category is shown to be compatible with the smash product of spectra. The method used is related to techniques developed by the author in earlier joint work with Roitzheim. That work constructed a monoidal model structure on Franke's exotic model for the K_(p)--local stable homotopy category. A monoidal Quillen equivalence to a simpler monoidal model category that has explicit generating sets is also given. Having monoidal model structures on the two categories removes a serious obstruction to constructing a series of monoidal Quillen equivalences between the algebraic model and rational SO(2)--equivariant spectra.

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OBJECTIVES: Radiotherapy is planned to achieve the optimal physical dose distribution to the target tumour volume whilst minimising dose to the surrounding normal tissue. Recent in vitro experimental evidence has demonstrated an important role for intercellular communication in radiobiological responses following non-uniform exposures. This study aimed to model the impact of these effects in the context of techniques involving highly modulated radiation fields or spatially fractionated treatments such as GRID therapy.

METHODS: Using the small animal radiotherapy research platform (SARRP) as a key enabling technology to deliver precision imaged-guided radiotherapy, it is possible to achieve spatially modulated dose distributions that model typical clinical scenarios. In this work, we planned uniform and spatially fractionated dose distributions using multiple isocentres with beam sizes of 0.5 - 5 mm to obtain 50% volume coverage in a subcutaneous murine tumour model, and applied a model of cellular response that incorporates intercellular communication to assess the potential impact of signalling effects with different ranges.

RESULTS: Models of GRID treatment plans which incorporate intercellular signalling showed increased cell killing within the low dose region. This results in an increase in the Equivalent Uniform Dose (EUD) for GRID exposures compared to standard models, with some GRID exposures being predicted to be more effective than uniform delivery of the same physical dose.

CONCLUSIONS: This study demonstrates the potential impact of radiation induced signalling on tumour cell response for spatially fractionated therapies and identifies key experiments to validate this model and quantify these effects in vivo.

ADVANCES IN KNOWLEDGE: This study highlights the unique opportunities now possible using advanced preclinical techniques to develop a foundation for biophysical optimisation in radiotherapy treatment planning.