A modification of flattening filter free linac for IMRT.

PURPOSE: This study investigates the benefits of a modified flattening filter free (FFF) linac over the standard (STD) linac equipped with the flattening filter. Energy and angular spread of the electron beam of the FFF linac were modified. Modification of FFF beam parameters is explored to maximize the monitor unit efficiency and to minimize the head scatter in IMRT delivery for large target volumes or targets lying away from the central axis. METHODS: The EGSnrc code is used to model FFF and STD linacs and study basic beam properties for both linac types in various beam configurations. Increasing energy of FFF linac results in similar beam attenuation properties and maximized dose rate compared to STD linac. Matching beam attenuation properties allows a more direct exploration of beam flatness of FFF linac in regard to IMRT delivery, especially away from the central axis where the effective dose rate is considerably smaller than the one at the central axis. Flatness of open beam dose profile of FFF linac is improved by increasing the angular spread of the electron beam. The resulting dose rate within the treatment field and outside of the field (peripheral dose) are characterized and compared to the unmodified FFF and STD linacs, RESULTS: In order to match beam penetration properties, the energy of FFF is adjusted from 6.5 to 8.0 MeV for small to medium field sizes and from 6.5 to 8.5 MeV for larger ones. Dose rate of FFF vs STD linac increased by a factor of 1.9 (6.5 MeV) and 3.4-4.1 (8.0-8.5 MeV). Adjusting the mean angular spread of the electron beam from 0 degrees to 5 degrees-10 degrees resulted in complete flattening of photon beam for field sizes between 10 x 10 cm2 and 15 x 15 cm2 and partial flattening for field sizes from 15 x 15 cm2 to 30 x 30 cm2. Values of angular spread > or =14 degrees are not recommended as they exceed the opening of the primary collimator, affecting the area at the edges of the field. FFF fields of sizes smaller than 6 x 6 cm2 are already flat and beam flattening is not necessary. Overall, the angular spread of 5 degrees-10 degrees is sufficient and can satisfactorily flatten open beam dose profiles even for larger field sizes. Increasing the electron beam angular spread amounts to a slight decrease of dose rate of FFF linac. However, for angular spread, 5 degrees-10 degrees dose rate factor of FFF vs STD is still about 1.6-2.6, depending on the field size (and the adjusted energy). Similarly, in case of peripheral dose, a moderate increase in dose can be observed for angular spread of 5 degrees-10 degrees and for field sizes 10 x 10 cm2 to 30 x 30 cm2. Lastly, beam flatness of not modified FFF linac can be conveniently described by an analytical function representing a ratio of STD vs FFF doses: 1 + b|r|(n). CONCLUSIONS: A modified FFF beamline with increased energy and electron beam angular spread results in satisfactory flattened beam and high dose rate within the field. Peripheral dose remaining at similar (or smaller) level than that of STD linac for the same delivered dose within the treatment field.

Comprehensive quality assurance phantom for the small animal radiation research platform (SARRP).

PURPOSE: To develop and test the suitability and performance of a comprehensive quality assurance (QA) phantom for the Small Animal Radiation Research Platform (SARRP). METHODS AND MATERIALS: A QA phantom was developed for carrying out daily, monthly and annual QA tasks including: imaging, dosimetry and treatment planning system (TPS) performance evaluation of the SARRP. The QA phantom consists of 15 (60 × 60 × 5 mm(3)) kV-energy tissue equivalent solid water slabs. The phantom can incorporate optically stimulated luminescence dosimeters (OSLD), Mosfet or film. One slab, with inserts and another slab with hole patterns are particularly designed for image QA. RESULTS: Output constancy measurement results showed daily variations within 3%. Using the Mosfet in phantom as target, results showed that the difference between TPS calculations and measurements was within 5%. Annual QA results for the Percentage depth dose (PDD) curves, lateral beam profiles, beam flatness and beam profile symmetry were found consistent with results obtained at commissioning. PDD curves obtained using film and OSLDs showed good agreement. Image QA was performed monthly, with image-quality parameters assessed in terms of CBCT image geometric accuracy, CT number accuracy, image spatial resolution, noise and image uniformity. CONCLUSIONS: The results show that the developed QA phantom can be employed as a tool for comprehensive performance evaluation of the SARRP. The study provides a useful reference for development of a comprehensive quality assurance program for the SARRP and other similar small animal irradiators, with proposed tolerances and frequency of required tests.

N,N-diethylphenylacetamide in treated fabrics as a repellent against Aedes aegypti and Culex quinquefasciatus (Diptera: Culicidae).

The efficacy of fabrics impregnated with N,N-diethylphenylacetamide (DEPA), a new repellent, was studied in the laboratory and field against Aedes aegypti (L.) and Culex quinquefasciatus Say. DEPA-treated polyester cotton and cotton fabrics provided repellency for 30 and 36 d and had a half-life of 11 and 5 d, respectively. The repellent could not be applied at a rate of greater than 15% of fabric weight. DEPA-treated fabric patches were found to be a practical and novel approach and were effective for 90 d in the laboratory against Ae. aegypti and 77 d in the field against Cs. quinquefasciatus.

Kilovoltage beam model for flat panel imaging system with bow-tie filter for scatter prediction and correction.

PURPOSE: Kilovoltage flat-panel imaging systems are used for cone-beam Computed Tomography (CBCT) and digital Tomosynthesis (DTS). Hereby, the presence of scatter and relatively large dose from imaging are challenging factors. In this study a phenomenological beam model was developed to characterize imager response to imaging beams with a bow-tie filter (Varian OBI system). MATERIALS AND METHOD: The kilovoltage beam model was based on dose ratio formalism and thus was using standard concepts of megavoltage dose calculation such as scatter factors, tissue maximum ratio and off-axis ratio. Primary and scatter (head and phantom scatter) were modeled with three Gaussian kernels. Parameters were based on measured transmission images for slabs of solid water of different total thickness and various jaw settings. RESULTS: The beam model was used to evaluate contributions from primary, secondary and tertiary contributions for different geometrical objects such as cylinders and step-like phantoms. Theoretical predictions of radiographs using the model for known objects are consistent with the measurements. CONCLUSION: Secondary and tertiary contributions were interpreted as scatter and can be subtracted from CBCT projections based on the analytical model. Therefore our model can provide a basis for improvement of image quality (less artifacts due to scatter, better contrast and resolution) in CBCT reconstruction.

3'- and 5'-strand cleavage reactions catalyzed by the Fpg protein from Escherichia coli occur via successive beta- and delta-elimination mechanisms, respectively.

The Fpg protein from Escherichia coli is a multifunctional protein that excises damaged purine bases from DNA to generate aldehydic abasic sites and then catalyzes the successive cleavage of the phosphodiester bonds first on the 3'-side and then on the 5'-side of the abasic site to generate 5'- and 3'-phosphate ends, respectively, thereby excising the deoxyribose residue. The mechanisms of the 3'- and 5'-strand cleavage reactions have been studied by nuclear magnetic resonance spectroscopy (NMR) and gas chromatography-mass spectrometry (GC-MS). The 3'-strand cleavage reaction is a beta-elimination reaction in which the 2'-hydrogen is abstracted and the 3'-phosphate is eliminated. The 5'-strand cleavage reaction is a delta-elimination reaction in which the 4'-hydrogen is abstracted and the 5'-phosphate is eliminated. Two types of experiments were performed to establish the occurrence of the sequential elimination reactions. First, when the reaction was performed in H2(18)O, 31P NMR demonstrated that neither phosphate group contained 18O. Second, the five-carbon product derived from the deoxyribose residue was stabilized by reduction with NaBH4 and characterized by GC-MS. The mass spectrum of the reduced product was identical to that of authentic 4-oxo-2-pentenal, the tautomerized product of successive beta- and delta-elimination reactions.

Bacteriophage T4 RNase H removes both RNA primers and adjacent DNA from the 5' end of lagging strand fragments.

Bacteriophage T4 RNase H belongs to a family of prokaryotic and eukaryotic nucleases that remove RNA primers from lagging strand fragments during DNA replication. Each enzyme has a flap endonuclease activity, cutting at or near the junction between single- and double-stranded DNA, and a 5'- to 3'-exonuclease, degrading both RNA.DNA and DNA.DNA duplexes. On model substrates for lagging strand synthesis, T4 RNase H functions as an exonuclease removing short oligonucleotides, rather than as an endonuclease removing longer flaps created by the advancing polymerase. The combined length of the DNA oligonucleotides released from each fragment ranges from 3 to 30 nucleotides, which corresponds to one round of processive degradation by T4 RNase H with 32 single-stranded DNA-binding protein present. Approximately 30 nucleotides are removed from each fragment during coupled leading and lagging strand synthesis with the complete T4 replication system. We conclude that the presence of 32 protein on the single-stranded DNA between lagging strand fragments guarantees that the nuclease will degrade processively, removing adjacent DNA as well as the RNA primers, and that the difference in the relative rates of synthesis and hydrolysis ensures that there is usually only a single round of degradation during each lagging strand cycle.

The 5'-exonuclease activity of bacteriophage T4 RNase H is stimulated by the T4 gene 32 single-stranded DNA-binding protein, but its flap endonuclease is inhibited.

Bacteriophage T4 RNase H is a 5'- to 3'-nuclease that has exonuclease activity on RNA.DNA and DNA.DNA duplexes and can remove the pentamer RNA primers made by the T4 primase-helicase (Hollingsworth, H. C., and Nossal, N. G. (1991) J. Biol. Chem. 266, 1888-1897; Hobbs, L. J., and Nossal, N. G. (1996) J. Bacteriol. 178, 6772-6777). Here we show that this exonuclease degrades duplex DNA nonprocessively, releasing a single oligonucleotide (nucleotides 1-4) with each interaction with the substrate. Degradation continues nonprocessively until the enzyme stops 8-11 nucleotides from the 3'-end of the substrate. T4 gene 32 single-stranded DNA-binding protein strongly stimulates the exonuclease activity of T4 RNase H, converting it into a processive nuclease that removes multiple short oligonucleotides with a combined length of 10-50 nucleotides each time it binds to the duplex substrate. 32 protein must bind on single-stranded DNA behind T4 RNase H for processive degradation. T4 RNase H also has a flap endonuclease activity that cuts preferentially on either side of the junction between single- and double-stranded DNA in flap and fork DNA structures. In contrast to the exonuclease, the endonuclease is inhibited completely by 32 protein binding to the single strand of the flap substrate. These results suggest an important role for T4 32 protein in controlling T4 RNase H degradation of RNA primers and adjacent DNA during each lagging strand cycle.

Identification of residues of T4 RNase H required for catalysis and DNA binding.

Bacteriophage T4 RNase H, which removes the RNA primers that initiate lagging strand fragments, has a 5'- to 3'-exonuclease activity on DNA.DNA and RNA.DNA duplexes and an endonuclease activity on flap or forked DNA structures (Bhagwat, M., Hobbs, L. J., and Nossal, N. J. (1997) J. Biol. Chem. 272, 28523-28530). It is a member of the RAD2 family of prokaryotic and eukaryotic replication and repair nucleases. The crystal structure of T4 RNase H, in the absence of DNA, shows two Mg2+ ions coordinated to the amino acids highly conserved in this family. It also shows a disordered region proposed to be involved in DNA binding (Mueser, T. C., Nossal, N. G., and Hyde, C. C. Cell (1996) 85, 1101-1112). To identify the amino acids essential for catalysis and DNA binding, we have constructed and characterized three kinds of T4 RNase H mutant proteins based on the possible roles of the amino acid residues: mutants of acidic residues coordinated to each of the two Mg2+ ions (Mg2+-1: D19N, D71N, D132N, and D155N; and Mg2+-2: D157N and D200N); mutants of conserved basic residues in or near the disordered region (K87A and R90A); and mutants of residues with hydroxyl side chains involved in the hydrogen bonding network (Y86F and S153A). Our studies show that Mg2+-1 and the residues surrounding it are important for catalysis and that Lys87 is necessary for DNA binding.