Dynamic control of laser driven proton beams by exploiting self-generated, ultrashort electromagnetic pulses

As part of the ultrafast charge dynamics initiated by high intensity laser irradiations of solid targets,high amplitude EM pulses propagate away from the interaction point and are transported along anystalks and wires attached to the target. The propagation of these high amplitude pulses along a thinwire connected to a laser irradiated target was diagnosed via the proton radiography technique,measuring a pulse duration of 20 ps and a pulse velocity close to the speed of light. The strongelectric field associated with the EM pulse can be exploited for controlling dynamically the protonbeams produced from a laser-driven source. Chromatic divergence control of broadband laser drivenprotons (upto 75% reduction in divergence of >5 MeV protons) was obtained by winding the supportingwire around the proton beam axis to create a helical coil structure. In addition to providingfocussing and energy selection, the technique has the potential to post-accelerate the transiting protonsby the longitudinal component of the curved electric field lines produced by the helical coil lens.

Tooth replacement for partially dentate elders: a willingness-to-pay analysis

Objectives: The primary aim of this study was to investigate partially dentate elders' willingness-to-pay (WTP) for two different tooth replacement strategies: Removable Partial Dentures (RPDs) and, functionally orientated treatment according to the principles of the Shortened Dental Arch (SDA). The secondary aim was to measure the same patient groups' WTP for dental implant treatment.Methods: 55 patients who had completed a previous RCT comparing two tooth replacement strategies (RPDs (n=27) and SDA (n=28)) were recruited (Trial Registration no. ISRCTN26302774). Patients were asked to indicate their WTP for treatment to replace missing teeth in a number of hypothetical scenarios using the payment card method of contingency evaluation coupled to different costs. Data were collected on patients' social class, income levels and other social circumstances. A Mann-Whitney U Test was used to compare differences in WTP between the two treatment groups. To investigate predictive factors for WTP, multiple linear regression analyses were conducted.Results: The median age for the patient sample was 72.0 years (IQR: 71-75 years). Patients who had been provided with RPDs indicated that their WTP for this treatment strategy was significantly higher (€550; IQR: 500-650) than those patients who had received SDA treatment (€500; IQR: 450-550) (p=0.003). However patients provided with RPDs indicated that their WTP for SDA treatment (€650; IQR: 600-650) was also significantly higher than those patients who had actually received functionally orientated treatment (€550; IQR: 500-600) (p<0.001). The results indicated that both current income levels and previous treatment allocation were significantly correlated to WTP for both the RPD and the SDA groups. Patients in both treatment groups exhibited little WTP for dental implant treatment with a median value recorded which was half the market value for this treatment (€1000; IQR: 500-1000).Conclusions: Amongst this patient cohort previous treatment experience had a strong influence on WTP as did current income levels. Both treatment groups indicated a very strong WTP for simpler, functionally orientated care using adhesive fixed prostheses (SDA) over conventional RPDs. Clinical significance: Partially dentate older patients expressed a strong preference for functionally orientated tooth replacement as an alternative to conventional RPDs.

Insight into the mechanism of galactokinase: role of a critical glutamate residue and helix/coil transitions

Galactokinase, the enzyme which catalyses the first committed step in the Leloir pathway, has attracted interest due to its potential as a biocatalyst and as a possible drug target in the treatment of type I galactosemia. The mechanism of the enzyme is not fully elucidated. Molecular dynamics (MD) simulations of galactokinase with the active site residues Arg-37 and Asp-186 altered predicted that two regions (residues 174-179 and 231-240) had different dynamics as a consequence. Interestingly, the same two regions were also affected by alterations in Arg-105, Glu-174 and Arg- 228. These three residues were identified as important in catalysis in previous computational studies on human galactokinase. Alteration of Arg-105 to methionine resulted in a modest reduction in activity with little change in stability. When Arg-228 was changed to methionine, the enzyme’s interaction with both ATP and galactose was affected. This variant was significantly less stable than the wild-type protein. Changing Glu-174 to glutamine (but not to aspartate) resulted in no detectable activity and a less stable enzyme. Overall, these combined in silico and in vitro studies demonstrate the importance of a negative charge at position 174 and highlight the critical role of the dynamics in to key regions of the protein. We postulate that these regions may be critical for mediating the enzyme’s structure and function.