Biomedical subjects

M Birkner

Publications and source records attributed to M Birkner.

3 recordsLinked to original sources

PubMed2002

Tools for the analysis of dose optimization: II. Sensitivity analysis.

Dose optimization requires that the treatment goals be specified in a meaningful manner, but also that alterations to the specification lead to predictable changes in the resulting dose distribution. Within the framework of constrained optimization, it is possible to devise a tool that quantifies the impact on the objective of target volume coverage of any change to a dosimetric constraint of normal tissue or target dose homogeneity. This sensitivity analysis relies on properties of the Lagrange function that is associated with the constrained optimization problem, but does not depend on the method used to solve this problem. It is useful particularly in cases with multiple target volumes and critical normal structures, where constraints and objectives can interact in a non-intuitive manner.

Algorithms↗

PubMed2000

Monte Carlo dose computation for IMRT optimization.

A method which combines the accuracy of Monte Carlo dose calculation with a finite size pencil-beam based intensity modulation optimization is presented. The pencil-beam algorithm is employed to compute the fluence element updates for a converging sequence of Monte Carlo dose distributions. The combination is shown to improve results over the pencil-beam based optimization in a lung tumour case and a head and neck case. Inhomogeneity effects like a broader penumbra and dose build-up regions can be compensated for by intensity modulation.

Algorithms↗

PubMed1995

Properties of modified hepatitis B virus surface antigen particles carrying preS epitopes.

The current hepatitis B virus (HBV) vaccines contain the small (S) and middle (M) viral envelope proteins in particulate form but lack the large (L) protein. Although these particles elicit protective immunity to HBV, inclusion of the immunogenic preS1 region of the L protein may enhance their efficacy. To present preS1-derived epitopes on secretable subviral particles we rearranged the HBV envelope ORF by fusing part or all of the preS1 region to either the N or C terminus of the S protein. Fusion of the first 42 residues of preS1 to either site allowed efficient secretion of the modified particles and rendered the linked sequence accessible at the surface of the particle. Conversely, fusion of preS1 sequences to the C terminus of the M protein completely blocked secretion. This block to secretion could be rescued by provision of a heterologous N-terminal signal sequence. All these particles displayed preS1, preS2 and S protein antigenicity. In mice, each construct elicited high titres of preS1-specific antibodies which recognized the authentic L protein. Particles composed of the modified M protein also induced a preS2-specific response. Unexpectedly, however, neither particle elicited S protein-specific antibodies. Nonetheless, the genetic approach employed here represents a strategy to incorporate preS1-derived epitopes both in high density and in highly immunogenic form into their authentic carrier matrix.

Animals↗