A host of water-soluble enzymes are active at membrane surfaces and in association with membranes. Some of these enzymes are involved in signalling and in modification and remodelling of the membranes. A special class of enzymes, the phospholipases, and in particular secretory phospholipase A(2) (sPLA(2)), are only activated at the interface between water and membrane surfaces, where they lead to a break-down of the lipid molecules into lysolipids and free fatty acids. The activation is critically dependent on the physical properties of the lipid-membrane substrate. A topical review is given of our current understanding of the physical mechanisms responsible for activation of sPLA(2) as derived from a range of different experimental and theoretical investigations.

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Purpose: A 1.5 T MR Linac (MRL) has recently become available. MRL treatment workflows (WF) include online plan adaptation based on daily MR images (MRI). This study reports initial clinical experiences after five months of use in terms of patient compliance, cases, WF timings, and dosimetric accuracy. Method and materials: Two different WF were used dependent on the clinical situation of the day; Adapt To Position WF (ATP) where the reference plan position is adjusted rigidly to match the position of the targets and the OARs, and Adapt To Shape WF (ATS), where a new plan is created to match the anatomy of the day, using deformable image registration. Both WFs included three 3D MRI scans for plan adaptation, verification before beam on, and validation during IMRT delivery. Patient compliance and WF timings were recorded. Accuracy in dose delivery was assessed using a cylindrical diode phantom. Results: 19 patients have completed their treatment receiving a total of 176 fractions. Cases vary from prostate treatments (60 Gy/20F) to SBRT treatments of lymph nodes (45 Gy/3F) and castration by ovarian irradiation (15 Gy/3F). The median session time (patient in to patient out) for 127 ATPs was 26[21-78] min, four fractions lasted more than 45 minutes due to additional plan adaptation. For the 49 ATSs a median time of 12[1-24] min was used for contouring resulting in a total median session time of 42[29-91] min. Three SBRT fractions lasted more than an hour. The time on the MRL couch was well tolerated by the patients. The median gamma pass rate (2mm,2% global max) for the adapted plans was 99.2[93.4-100]%, showing good agreement between planned and delivered dose. Conclusion: MRL treatments, including daily MRIs, plan adaptation and accurate dose delivery is possible within a clinically acceptable timeframe and is well tolerated by the patients.

The nucleation and growth of solid domains in supported bilayers composed of a binary mixture of equimolar 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) have been studied using combined fluorescence microscopy and AFM. We have found that the formation of the DPPC-enriched solid domains occurs by a combination of homogeneous and heterogeneous nucleation and that the nucleation density is directly proportional to the cooling rate. Furthermore, during cooling the shape of the domains evolve from compact to a branched morphology. This suggests that the growth is controlled by the diffusion of DPPC from the liquid phase toward the solid domain interface. In the late stages of the growth, we observe that the size and overall shape of the domains depend on the position of the nucleation points relative to the surrounding nucleation point positions. To analyze this effect, the nucleation points were used as generators in a Voronoi construction. Associated with each generator is a Voronoi polygon that contains all points closer to this generator than to any other. Through a detailed quantitative analysis of the Voronoi cells and the domains, we have found that their area, orientation, and asymmetry correlate and that the correlation becomes stronger for larger domains. This means that the spatial distribution of the nucleation points regulate the domain shape.