Reference dosimetry can be performed with integrated MRIgRT devices by using magnetic field correction factors, but care must be taken with the choice of beam quality specifier and chamber orientation. The uncertainties achievable under this formalism should be similar to those of conventional formalisms, although this must be further quantified.

CTP synthetase (EC 6.3.4.2, UTP:ammonia ligase (ADP-forming)) activity in Saccharomyces cerevisiae is allosterically regulated by CTP product inhibition. Amino acid residue Glu 161 in the URA7-encoded and URA8-encoded CTP synthetases was identified as being involved in the regulation of these enzymes by CTP product inhibition. The specific activities of the URA7-encoded and URA8-encoded enzymes with a Glu 161 3 Lys (E161K) mutation were 2-fold greater when compared with the wild-type enzymes. The E161K mutant URA7-encoded and URA8-encoded CTP synthetases were less sensitive to CTP product inhibition with inhibitor constants for CTP of 8.4-and 5-fold greater, respectively, than those of their wild-type counterparts. Cells expressing the E161K mutant enzymes on a multicopy plasmid exhibited an increase in resistance to the pyrimidine poison and cancer therapeutic drug cyclopentenylcytosine and accumulated elevated (6 -15-fold) levels of CTP when compared with cells expressing the wild-type enzymes. Cells expressing the E161K mutation in the URA7-encoded CTP synthetase exhibited an increase (1.5-fold) in the utilization of the Kennedy pathway for phosphatidylcholine synthesis when compared with control cells. Cells bearing the mutation also exhibited an increase in the synthesis of phosphatidylcholine (1.5-fold), phosphatidylethanolamine (1.3-fold), and phosphatidate (2-fold) and a decrease in the synthesis of phosphatidylserine (1.7-fold). These alterations were accompanied by an inositol excretion phenotype due to the misregulation of the INO1 gene. Moreover, cells bearing the E161K mutation exhibited an increase (1.6-fold) in the ratio of total neutral lipids to phospholipids, an increase in triacylglycerol (1.4-fold), free fatty acids (1.7-fold), and ergosterol ester (1.8-fold), and a decrease in diacylglycerol (1.3-fold) when compared with control cells. These data indicated that the regulation of CTP synthetase activity by CTP plays an important role in the regulation of phospholipid synthesis.CTP synthetase (EC 6.3.4.2, UTP:ammonia ligase (ADPforming)) is a cytosolic-associated glutamine amidotransferase that catalyzes the ATP-dependent transfer of the amide nitrogen from glutamine to the C-4 position of UTP to form CTP (1, 2). This enzyme plays an essential role in the synthesis of all membrane phospholipids in eukaryotic cells (3, 4). Its reaction product CTP is the direct precursor of the activated, energyrich phospholipid pathway intermediates CDP-DG 1 (5), CDPcholine (6), and CDP-ethanolamine (6) (Fig. 1). CDP-DG is the source of the phosphatidyl moiety of PS, PE, and PC synthesized by the CDP-DG pathway as well as PI, phosphatidylglycerol, and cardiolipin (3, 4). CDP-choline and CDP-ethanolamine are the sources of the hydrophilic head groups of PC and PE synthesized by the Kennedy pathways, respectively (3, 4). Our laboratory utilizes the yeast Saccharomyces cerevisiae as a model eukaryote to study the regulation of CTP synthetase and its impact on phospholipid metabolism. CTP synthetase is encoded by ...

The magnetic field of the MR-linac alters the effective point of measurement of ionization chambers, shifting it both downstream and laterally. Shielded diodes produce incorrect and misleading dose profiles. The output factor measured at the point of peak intensity in the lateral dose distribution is more robust than the conventional output factor (measured at central axis). Diodes are not recommended for output factor measurements in the magnetic field.

Purpose The aim of this study was to examine the effect of sub-millimeter air gaps that may exist between an ionization chamber and solid phantoms when measurements are performed in a magnetic field. Methods Geant4 Monte Carlo simulations were performed using a model of a PTW 30013 Farmer chamber in a water phantom. Symmetrical and asymmetrical air gaps of various thicknesses were modeled surrounding the chamber, and the dose to the air cavity of the chamber was scored in each case. Magnetic fields were modeled parallel to the long axis of the chamber with strengths of 0, 0.35 T, 1.0 T and 1.5 T. To examine the phenomenon in more detail, the gyroradii of the electrons responsible for the energy deposited in the chamber were scored as they entered the chamber and the total energy deposited was split into three components: energy originating from inside the chamber, in the immediate vacinity of the chamber, or outside the chamber. Results Differences in the chamber dose of 1.6% were observed for asymmetric air gaps just 0.2 mm thick. No effect greater than 0.5% was observed for the symmetrical air gaps investigated in this work (1.4 mm thick or less) for this chamber/magnetic field configuration. The mean gyroradius of contributing electrons as they first enter the chamber was 4 mm. The presence of the air gap reduced the energy contributions from electrons released in the immediate vicinity of the chamber, and this loss was not completely compensated for when a magnetic field is present. Conclusions The gyroradius of most electrons was too large to be responsible for the air gap effect via the electron return effect; instead, the effect is attributed to the loss of energy contributions from electrons originating inside the air gap volume, which is not completely compensated for by more distant electrons owing to their reduced range in the magnetic field. When the chamber is parallel with the magnetic field, symmetric air gaps have a smaller effect (<0.5%) compared to asymmetric air-gaps (up to 1.6%) in the chamber response.

Detector correction factors based solely on empirical measurement or numerical calculation are subject to potential bias. A semiempirical approach, combining both empirical and numerical data, provided the most reliable results.