Treatments delivered by proton therapy are affected by uncertainties on the range of the beam within the patient, requiring medical physicists to add safety margins on the penetration depth of the beam. To reduce these margins and deliver safer treatments, different projects are currently investigating real-time range control by imaging prompt gammas emitted along the proton tracks in the patient. This study reports on the feasibility, development and test of a new concept of prompt gamma camera using a slit collimator to obtain a one-dimensional projection of the beam path on a scintillation detector. This concept was optimized, using the Monte Carlo code MCNPX version 2.5.0, to select high energy photons correlated with the beam range and detect them with both high statistics and sufficient spatial resolution. To validate the Monte Carlo model, spectrometry measurements of secondary particles emitted by a PMMA target during proton irradiation at 160 MeV were realized. An excellent agreement with the simulations was observed when using subtraction methods to isolate the gammas in direct incidence. A first prototype slit camera using the HiCam gamma detector was consequently prepared and tested successfully at 100 and 160 MeV beam energies. Results confirmed the potential of this concept for real-time range monitoring with millimetre accuracy in pencil beam scanning mode for typical clinical conditions. If we neglect electronic dead times and rejection of detected events, the current solution with its collimator at 15 cm from the beam axis can achieve a 1-2 mm standard deviation on range estimation in a homogeneous PMMA target for numbers of protons that correspond to doses in water at the Bragg peak as low as 15 cGy at 100 MeV and 25 cGy at 160 MeV assuming pencil beams with a Gaussian profile of 5 mm sigma at target entrance.

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The Poisson-Boltzmann method was used to compute the pK(a) values of titratable residues in a set of class C beta-lactamases. In these calculations, the pK(a) of the phenolic group of residue Tyr150 is the only one to stand out with an abnormally low value of 8.3, more than one pK(a) unit lower than the measured reference value for tyrosine in solution. Other important residues of the catalytic pocket, such as the conserved Lys67, Lys315, His314, and Glu272 (hydrogen-bonded to the ammonium group of Lys315), display normal protonation states at neutral pH. pK(a) values were also computed in catalytically impaired beta-lactamase mutants. Comparisons between the relative k(cat) values and the Tyr150 pK(a) value in these mutants revealed a striking correlation. In active enzymes, this pK(a) value is always lower than the solution reference value while it is close to normal in inactive enzymes. These results thus support the hypothesis that the phenolate form of Tyr150 is responsible for the activation of the nucleophilic serine. The possible roles of Lys67 and Lys315 during catalysis are also discussed.

We define the interface excitation parameter (IEP) as the change in excitation probability, caused by the presence of a medium‐medium interface crossed by an electron, in comparison with an electron for which only bulk excitations are considered. This definition is established by analogy with the definition of the surface excitation parameter for which one of the two media of the interface is the vacuum and which has already been extensively studied. To calculate the IEP (as well as the energy‐differential IEP or DIEP), we generalize the model developed by Tung, Chen, Kwei and Chou [C. J. Tung, Y. F. Chen, C. M. Kwei and T. L. Chou, Phys. Rev. B 49 (1994) 16684] from dielectric response theory for surface excitation parameter determination. We perform these calculations for angles between 0o and 60o, for electron energies between 200 and 3000eV and for various combinations of materials, chosen for their academic (as Al/In) or practical interest (as SiO2/Si for instance). We show that for materials with “similar” dielectric properties (metal/metal), the IEP is completely negligible. On the contrary when the materials of the interface are characterized by a large energy band gap difference, as metal/insulator or semiconductor/insulator, the IEP can reach a value of about 0.26 for the smallest electron energies considered here. Moreover, we show that for the SiO2/Si interface, the energy‐differential IEP obtained from our model is in good agreement with previous experimental data. Copyright © 2015 John Wiley & Sons, Ltd.