Effect of modulation factor and low dose threshold level on gamma pass rates of single isocenter multi-target SRT treatment plans.

PURPOSE: SRS MapCHECK (SMC) is a commercially available patient-specific quality assurance (PSQA) tool for stereotactic radiosurgery (SRS) applications. This study investigates the effects of degree of modulation, location off-axis, and low dose threshold (LDT) selection on gamma pass rates (GPRs) between SMC and treatment planning system, Analytical Anisotropic Algorithm (AAA), or Vancouver Island Monte Carlo (VMC++ algorithm) system calculated dose distributions. METHODS: Volumetric-modulated arc therapy (VMAT) plans with modulation factors (MFs) ranging from 2.7 to 10.2 MU/cGy were delivered to SMC at isocenter and 6 cm off-axis. SMC measured dose distributions were compared against AAA and VMC++ via gamma analysis (3%/1 mm) with LDT of 10% to 80% using SNC Patient software. RESULTS: Comparing on-axis SMC dose against AAA and VMC++ with LDT of 10%, all AAA-calculated plans met the acceptance criteria of GPR ≥ 90%, and only one VMC++ calculated plan was marginally outside the acceptance criteria with pass rate of 89.1%. Using LDT of 80% revealed decreasing GPR with increasing MF. For AAA, GPRs reduced from 100% at MF of 2.7 MU/cGy to 57% at MF of 10.2 MU/cGy, and for VMC++ calculated plans, the GPRs reduced from 89% to 60% in the same MF range. Comparison of SMC dose off-axis against AAA and VMC++ showed more pronounced reduction of GPR with increasing MF. For LDT of 10%, AAA GPRs reduced from 100% to 83% in the MF range of 2.7 to 9.8 MU/cGy, and VMC++ GPR reduced from 100% to 91% in the same range. With 80% LDT, GPRs dropped from 100% to 42% for both algorithms. CONCLUSIONS: MF, dose calculation algorithm, and LDT selections are vital in VMAT-based SRT PSQA. LDT of 80% enhances sensitivity of gamma analysis for detecting dose differences compared to 10% LDT. To achieve better agreement between calculated and SMC dose, it is recommended to limit the MF to 4.6 MU/cGy on-axis and 3.6 MU/cGy off-axis.

Total body irradiation of bone marrow transplant using helical TomoTherapy with a focus on the quality of dose contribution at junction target volumes.

PURPOSE: Total body irradiation (TBI) can be safely delivered on TomoTherapy (Accuray, Sunnyvale, CA, USA) in both pediatric and adult patients with proper imaging and planning despite the length constraint of 135 cm. To overcome this limitation, two CT (Computed Tomography) scans (CT1& CT2) are taken in patients above 135 cm in height. Adequate junction dose coverage is important in TBI. Presently, there is no clinical report with a focus on the quality of dose distribution at the CT junction in view of the guidelines on quality of coverage from the RTOG. Hence, our main objectives were to evaluate the dose distribution and quality of coverage at the junction in 16 patients who received TBI using TomoTherapy. METHODS: PTV(upper) and PTV(lower) along with a junction were created on CT1 and CT2, respectively. Subsequently, the 10 cm junction in the thigh region was divided into five target volumes of 2 cm thickness with dose prescription ranging from 10 to 90% to deliver a total dose equal to 100% when fused. RESULTS: The D50 was equal to the prescribed dose in most of the cases ranging from 99.5 to 104% for PTV(upper), 100-103% for PTV(lower), and 99.5-108% for junctional PTVs (1PTV, 2PTV, 3PTV, 4PTV, and 5PTV). The average D95 doses from PTV(upper) and PTV(lower) were 97 ± 1.4% and 96.7 ± 1.08%, respectively. The average D95 doses for 1PTV, 2PTV, 3PTV, 4PTV, and 5PTV were 96.1 ± 1.88%, 91.6 ± 1.82%, 87.3 ± 1.5%, 91.6 ± 1.4%, and 96.2 ± 1.5% respectively. QRTOG values ranged between 0.85 and 1.05 and were in concordance with RTOG guidelines. CONCLUSION: Since junction-based planning was required for most TBI patients, it is essential to evaluate the quality of dose coverage in the junction for better TBI plans.

Functional Characterization of the Pseudomonas aeruginosa Ribosome Hibernation-Promoting Factor.

Hibernation-promoting factor (HPF) is a ribosomal accessory protein that inactivates ribosomes during bacterial starvation. In Pseudomonas aeruginosa, HPF protects ribosome integrity while the cells are dormant. The sequence of HPF has diverged among bacteria but contains conserved charged amino acids in its two alpha helices that interact with the rRNA. Here, we characterized the function of HPF in P. aeruginosa by performing mutagenesis of the conserved residues and then assaying mutant HPF alleles for their ability to protect ribosome integrity of starved P. aeruginosa cells. The results show that HPF functionally tolerates point mutations in charged residues and in the conserved Y71 residue as well as a C-terminal truncation. Double and triple mutations of charged residues in helix 1 in combination with a Y71F substitution reduce HPF activity. Screening for single point mutations that caused impaired HPF activity identified additional substitutions in the two HPF alpha helices. However, alanine substitutions in equivalent positions restored HPF activity, indicating that HPF is tolerant to mutations that do not disrupt the protein structure. Surprisingly, heterologous HPFs from Gram-positive bacteria that have long C-terminal domains functionally complement the P. aeruginosa Δhpf mutant, suggesting that HPF may play a similar role in ribosome protection in other bacterial species. Collectively, the results show that HPF has diverged among bacteria and is tolerant to most single amino acid substitutions. The Y71 residue in combination with helix 1 is important for the functional role of HPF in ribosome protection during bacterial starvation and resuscitation of the bacteria from dormancy.IMPORTANCE In most environments, bacteria experience conditions where nutrients may be readily abundant or where nutrients are limited. Under nutrient limitation conditions, even non-spore-forming bacteria may enter a dormant state. Dormancy is accompanied by a variety of cellular physiological changes that are required for the cells to remain viable during dormancy and to resuscitate when nutrients become available. Among the physiological changes that occur in dormant bacteria is the inactivation and preservation of ribosomes by the dormancy protein, hibernation-promoting factor (HPF). In this study, we characterized the activity of HPF of Pseudomonas aeruginosa, an opportunistic pathogen that causes persistent infections, and analyzed the role of HPF in ribosome protection and bacterial survival during dormancy.

Determining efficient helical IMRT modulation factor from the MLC leaf-open time distribution on precision treatment planning system.

PURPOSE: Since the modulation factor (MF) impacts both plan quality and delivery efficiency in tomotherapy Intensity Modulated Radiation Therapy (IMRT) treatment planning, the purpose of this study was to demonstrate a technique in determining an efficient MF from the Multileaf Collimator (MLC) leaf-open time (LOT) distribution of a tomotherapy treatment delivery plan. METHODS: Eight clinical plans of varying complexity were optimized with the highest allowed MF on the Accuracy Precision treatment planning system. Using a central limit theorem argument a range of reduced MFs were then determined from the first two moments of the LOT distribution. A step down approach was used to calculate the reduced-MF plans and plan comparison tools available on the Precision treatment planning system were used to evaluate dose differences with the reference plan. RESULTS: A reduced-MF plan that balanced delivery time and dosimetric quality was found from the set of five MFs determined from the LOT distribution of the reference plan. The reduced-MF plan showed good agreement with the reference plan (target and critical organ dose-volume region of interest dose differences were within 1% and 2% of prescription dose, respectively). DISCUSSION: Plan evaluation and acceptance criteria can vary depending on individual clinical expectations and dosimetric quality trade-offs. With the scheme presented in this paper a planner should be able to efficiently generate a high-quality plan with efficient delivery time without knowing a good MF beforehand. CONCLUSION: A methodology for deriving a reduced MF from the LOT distribution of a high MF treatment plan using the central limit theorem has been presented. A scheme for finding a reduced MF from a set of MFs that results in a plan balanced in both dosimetric quality and treatment delivery efficiency has also been presented.

Results of a 10-year survey of workload for 10 treatment vaults at a high-throughput comprehensive cancer center.

The workload for shielding purposes of modern linear accelerators (linacs) consists of primary and scatter radiation which depends on the dose delivered to isocenter (cGy) and leakage radiation which depends on the monitor units (MUs). In this study, we report on the workload for 10 treatment vaults in terms of dose to isocenter (cGy), monitor units delivered (MUs), number of treatment sessions (Txs), as well as, use factors (U) and modulation factors (CI) for different treatment techniques. The survey was performed for the years between 2006 and 2015 and included 16 treatment machines which represent different generations of Varian linear accelerators (6EX, 600C, 2100C, 2100EX, and TrueBeam) operating at different electron and x-ray energies (6, 9, 12, 16 and 20 MeV electrons and, 6 and 15 MV x-rays). An institutional review board (IRB) approval was acquired to perform this study. Data regarding patient workload, dose to isocenter, number of monitor units delivered, beam energies, gantry angles, and treatment techniques were exported from an ARIA treatment management system (Varian Medical Systems, Palo Alto, Ca.) into Excel spreadsheets and data analysis was performed in Matlab. The average (± std-dev) number of treatment sessions, dose to isocenter, and number of monitor units delivered per week per machine in 2006 was 119 ± 39 Txs, (300 ± 116) × 102 cGys, and (78 ± 28) × 103 MUs respectively. In contrast, the workload in 2015 was 112 ± 40 Txs, (337 ± 124) × 102 cGys, and (111 ± 46) × 103 MUs. 60% of the workload (cGy) was delivered using 6 MV and 30% using 15 MV while the remaining 10% was delivered using electron beams. The modulation factors (MU/cGy) for IMRT and VMAT were 5.0 (± 3.4) and 4.6 (± 1.6) respectively. Use factors using 90° gantry angle intervals were equally distributed (~0.25) but varied considerably among different treatment techniques. The workload, in terms of dose to isocenter (cGy) and subsequently monitor units (MUs), has been steadily increasing over the past decade. This increase can be attributed to increased use of high dose hypo-fractionated regimens (SBRT, SRS) and the increase in use of IMRT and VMAT, which require higher MUs per cGy as compared to more conventional treatment (3DCRT). Meanwhile, the patient workload in terms of treatment sessions per week remained relatively constant. The findings of this report show that variables used for shielding purposes still fall within the recommendation of NCRP Report 151.

Analysis of modulation factor to shorten the delivery time in helical tomotherapy.

A low modulation factor (MF) maintaining a good dose distribution contributes to the shortening of the delivery time and efficiency of the treatment plan in helical tomotherapy. The purpose of this study was to reduce the delivery time using initial values and the upper limit values of MF. First, patients with head and neck cancer (293 cases) or prostate cancer (181 cases) treated between June 2011 and July 2015 were included in the analysis of MF values. The initial MF value (MFinitial ) was defined as the average MFactual value, and the upper limit of the MF value (MFUL ) was defined according the following equation: MFUL = 2 × standard deviation of MFactual value + the average MFactual Next, a treatment plan was designed for patients with head and neck cancer (62 cases) and prostate cancer (13 cases) treated between December 2015 and June 2016. The average MFactual value for the nasopharynx, oropharynx, hypopharynx, and prostate cases decreased from 2.1 to 1.9 (p = 0.0006), 1.9 to 1.6 (p < 0.0001), 2.0 to 1.7 (p < 0.0001), and 1.8 to 1.6 (p = 0.0004) by adapting the MFinitial and the MFUL values, respectively. The average delivery time for the nasopharynx, oropharynx, hypopharynx, and prostate cases also decreased from 19.9 s cm-1 to 16.7 s cm-1 (p < 0.0001), 15.0 s cm-1 to 13.9 s cm-1 (p = 0.025), 15.1 s cm-1 to 13.8 s cm-1 (p = 0.015), and 23.6 s cm-1 to 16.9 s cm-1 (p = 0.008) respectively. The delivery time was shortened by the adaptation of MFinitial and MFUL values with a reduction in the average MFactual for head and neck cancer and prostate cancer cases.

The VrrA sRNA controls a stationary phase survival factor Vrp of Vibrio cholerae.

Small non-coding RNAs (sRNAs) are emerging regulatory elements in bacteria. The Vibrio cholerae sRNA VrrA has previously been shown to down-regulate outer membrane proteins (OmpA and OmpT) and biofilm matrix protein (RbmC) by base-pairing with the 5' region of the corresponding mRNAs. In this study, we present an additional target of VrrA in V. cholerae, the mRNA coding for the ribosome binding protein Vrp. Vrp is homologous to ribosome-associated inhibitor A (RaiA) of Escherichia coli which facilitates stationary phase survival through ribosome hibernation. We show that VrrA down-regulates Vrp protein synthesis by base-pairing to the 5' region of vrp mRNA and that the regulation requires the RNA chaperone protein, Hfq. We further demonstrate that Vrp is highly expressed during stationary phase growth and associates with the ribosome of V. cholerae. The effect of the Vrp protein in starvation survival is synergistic with that of the VC2530 protein, a homolog of the E. coli hibernation promoting factor HPF, suggesting a combined role for these proteins in ribosome hibernation in V. cholerae. Vrp and VC2530 are important for V. cholerae starvation survival under nutrient deficient conditions. While VC2530 is down-regulated in cells lacking vrrA, mutation of vrp results in VC2530 activation. This is the first report indicating a regulatory role for an sRNA, modulating stationary factors involved in bacterial ribosome hibernation.

Dosiomics-based detection of dose distribution variations in helical tomotherapy for prostate cancer patients: influence of treatment plan parameters.

The stability of dosiomics features (DFs) and dose-volume histogram (DVH) parameters for detecting disparities in helical tomotherapy planned dose distributions was assessed. Treatment plans of 18 prostate patients were recalculated using the followings: field width (WF) (2.5 vs. 5), pitch factor (PF) (0.433 vs. 0.444), and modulation factor (MF) (2.5 vs. 3). From each of the eight plans per patient, ninety-three original and 744 wavelet-based DFs were extracted, using 3D-Slicer software, across six regions including: target volume (PTV), pelvic lymph nodes (PTV-LN), PTV + PTV-LN (PTV-All), one cm rind around PTV-All (PTV-Ring), rectum, and bladder. For the resulting DFs and DVH parameters, the coefficient of variation (CV) was calculated, and using hierarchical clustering, the features were classified into low/high variability. The significance of parameters on instability was analyzed by a three-way analysis of variance. All DF's were stable in PTV, PTV-LN, and PTV-Ring (average CV ( CV ¯ )  ≤ 0.36). Only one feature in the bladder ( CV ¯  = 0.9), rectum ( CV ¯  = 0.4), and PTV-All ( CV ¯  = 0.37) were considered unstable due to change in MF in the bladder and WF in the PTV-All. The value of CV ¯ for the wavelet features was much higher than that for the original features. Out of 225 unstable wavelet features, 84 features had CV ¯  ≥ 1. The CVs for all the DVHs remained very small ( CV ¯ < 0.06). This study highlights that the sensitivity of DFs to changes in tomotherapy planning parameters is influenced by the region and the DFs, particularly wavelet features, surpassing the effectiveness of DVHs.

Optimal Combination of Pitch, Modulation Factor and Dosimetric Considerations in Treatment Planning for Total Body Irradiation Using Helical Tomotherapy.

OBJECTIVE: The aim of this study is to makethe standard total body irradiation (TBI) protocol for Helical tomotherapy© (HT) and to analyze the optimal pitch and modulation factor (MF) with respect to dose homogeneity index (HI), target dose coverage, target overdose, beam on time (BOT) and mean lung dose. MATERIALS AND METHODS: Ten patients who underwent high-dose TBI were taken for this study. For each patient, 35 dose plans were created by different combination of pitch and MF. The optimal pitch and MF were deduced using scatter plot and regression methodology based on target coverage, HI, target volume receiving 103%(V103%), 105%(V105%) and 107% (V107%) of the prescription dose and BOT. Using these optimal pitch and MF, the final dose plan was made and the planning aim and achieved dose was compared using two tailed student's t-test. Radiochromic films and ionization chambers were used to measure the delivered dose using anthropomorphic phantom on various points for the head and pelvis regions to verify the skin flash margin and its effect on skin dose. RESULTS: The optimal pitch and MF value were 0.287 and 2.4 respectively. Based on optimal pitch and MF, the mean BOT was 1692 seconds with optimal inhomogeneity (7.4%). For target, D95 and D98 were 97.09% (range:94.7-99.6%, p=0.002) and 93.9% (range:91.5-94.4%,p=0.007) respectively, and mean D2 was within 107% with SD of ±1.22% (p=0.04). The mean of PTV receiving V103, V105 and V107 was 24.48% (range=7.7-36.6%, p=0.03), 5.76% (range=1.4-12.1%, SD=±3.3%), 1.93% (range=0.1-4.6%, p=0.008) respectively. Our measurements show that the flash margin did not increase the skin dose. CONCLUSION: In our study, the optimal combination of pitch value of 0.287 and MF value of 2.4 provided acceptable plans for all patients planned for TBI in HT. The flash margin can provide adequate coverage during patient position uncertainty without increasing the skin dose.

Generation and Modulation of Controllable Multi-Focus Array Based on Phase Segmentation.

A Circular-Sectorial Phase Segmentation (CSPS) noniterative method for effectively generating and manipulating muti-focus array (MFA) was proposed in this work. The theoretical model of the CSPS was built up based on vectorial diffraction integral and the phase modulation factor was deduced with inverse fast Fourier transform. By segmenting the entrance pupil into specified regions, which were sequentially assigned with the values carried out by phase modulation factor, the methodology could generate flexible MFAs with desired position and morphology. Subsequently, the CSPS was investigated in parallelized fabrication with a laser direct writing system. The positioning accuracy was greater than 96% and the morphologic consistency of the parallelly fabricated results was greater than 92%.

Functional Sites of Ribosome Modulation Factor (RMF) Involved in the Formation of 100S Ribosome.

One of the important cellular events in all organisms is protein synthesis, which is catalyzed by ribosomes. The ribosomal activity is dependent on the environmental situation of the cell. Bacteria form 100S ribosomes, lacking translational activity, to survive under stress conditions such as nutrient starvation. The 100S ribosome is a dimer of two 70S ribosomes bridged through the 30S subunits. In some pathogens of gammaproteobacteria, such as Escherichia coli, Yersinia pestis, and Vibrio cholerae, the key factor for ribosomal dimerization is the small protein, ribosome modulation factor (RMF). When ribosomal dimerization by RMF is impaired, long-term bacterial survival is abolished. This shows that the interconversion system between active 70S ribosomes and inactive 100S ribosomes is an important survival strategy for bacteria. According to the results of several structural analyses, RMF does not directly connect two ribosomes, but binds to them and changes the conformation of their 30S subunits, thus promoting ribosomal dimerization. In this study, conserved RMF amino acids among 50 bacteria were selectively altered by mutagenesis to identify the residues involved in ribosome binding and dimerization. The activities of mutant RMF for ribosome binding and ribosome dimerization were measured using the sucrose density gradient centrifugation (SDGC) and western blotting methods. As a result, some essential amino acids of RMF for the ribosomal binding and dimerization were elucidated. Since the induction of RMF expression inhibits bacterial growth, the data on this protein could serve as information for the development of antibiotic or bacteriostatic agents.

Ribosomal Hibernation-Associated Factors in Escherichia coli.

Bacteria convert active 70S ribosomes to inactive 100S ribosomes to survive under various stress conditions. This state, in which the ribosome loses its translational activity, is known as ribosomal hibernation. In gammaproteobacteria such as Escherichia coli, ribosome modulation factor and hibernation-promoting factor are involved in forming 100S ribosomes. The expression of ribosome modulation factor is regulated by (p)ppGpp (which is induced by amino acid starvation), cAMP-CRP (which is stimulated by reduced metabolic energy), and transcription factors involved in biofilm formation. This indicates that the formation of 100S ribosomes is an important strategy for bacterial survival under various stress conditions. In recent years, the structures of 100S ribosomes from various bacteria have been reported, enhancing our understanding of the 100S ribosome. Here, we present previous findings on the 100S ribosome and related proteins and describe the stress-response pathways involved in ribosomal hibernation.

Fluence-weighted average subfield size in helical TomoTherapy.

INTRODUCTION: Helical TomoTherapy allows a highly conformal dose distribution to complex target geometries with a good protection of organs at risk. However, the small field sizes associated with this method are a possible source of dosimetrical uncertainties. The IAEA has published detector-specific field output correction factors for static fields of the TomoTherapy in the TRS483. This work investigates the average subfield size of helical TomoTherapy plans. MATERIAL AND METHODS: A new parameter for helical TomoTherapy was defined - the fluence-weighted average subfield size. The subfield sizes were extracted from the leaf-opening time sinograms in the RT-plan files for 30 clinical prostate and head and neck plans and were put in relation to Delat4 Phantom+ measurement results. Additionally the influence of planning parameters on the subfield size was studied by varying the modulation factor, number of iterations and pitch in the dose optimization and calculation for three different clinical indications H&N, prostate and rectum cancer. Selected plans were dosimetrically verified by Delta4 measurements to examine the reliability in dependence of the average subfield size. Furthermore, the impact of the planning parameters on a) the dose distribution, with regard to the planning target volume and regions at risks, and b) machine characteristics such as delivery time, actual modulation factor and leaf-opening times were evaluated. RESULTS: The average equivalent square subfield lengths (s¯eq) of the two investigated indications did not differ significantly - prostate plans: 2.75±0.14cm and H&N plans: 2.70±0.16cm, both with a jaw width of 2.5cm. No correlation between field size and measured dose deviation was detected. The number of iterations and the modulation factor have a considerable influence on the average subfield size. The higher the planned modulation factor and the more iterations are used during optimization, the smaller is the subfield size. In our pilot study plans were calculated with field sizes s¯eq between 4.2cm and 1.7cm, with a jaw width of 2.5cm. Again, the measurement results of Delta4 showed no significant deviation from the doses calculated by the TomoTherapy planning system for the whole range of subfield sizes, and no significant correlation between field sizes and dose deviations was found. As expected, the clinical dose distribution improved with increasing modulation factor and an increasing number of iterations. The compromise between an improved dose distribution and smaller s¯eq was shown. CONCLUSION: In this work, a method was presented to determine the average subfield size for helical TomoTherapy plans. The response of the Delta4 did not show any dependence on field size in the range of the field sizes covered by the studied plans. The influence of the subfield sizes on other dosimetry systems remains to be investigated.

Coordinated Regulation of Rsd and RMF for Simultaneous Hibernation of Transcription Apparatus and Translation Machinery in Stationary-Phase Escherichia coli.

Transcription and translation in growing phase of Escherichia coli, the best-studied model prokaryote, are coupled and regulated in coordinate fashion. Accordingly, the growth rate-dependent control of the synthesis of RNA polymerase (RNAP) core enzyme (the core component of transcription apparatus) and ribosomes (the core component of translation machinery) is tightly coordinated to keep the relative level of transcription apparatus and translation machinery constant for effective and efficient utilization of resources and energy. Upon entry into the stationary phase, transcription apparatus is modulated by replacing RNAP core-associated sigma (promoter recognition subunit) from growth-related RpoD to stationary-phase-specific RpoS. The anti-sigma factor Rsd participates for the efficient replacement of sigma, and the unused RpoD is stored silent as Rsd-RpoD complex. On the other hand, functional 70S ribosome is transformed into inactive 100S dimer by two regulators, ribosome modulation factor (RMF) and hibernation promoting factor (HPF). In this review article, we overview how we found these factors and what we know about the molecular mechanisms for silencing transcription apparatus and translation machinery by these factors. In addition, we provide our recent findings of promoter-specific transcription factor (PS-TF) screening of the transcription factors involved in regulation of the rsd and rmf genes. Results altogether indicate the coordinated regulation of Rsd and RMF for simultaneous hibernation of transcription apparatus and translation machinery.

Coordinated Hibernation of Transcriptional and Translational Apparatus during Growth Transition of Escherichia coli to Stationary Phase.

In the process of Escherichia coli K-12 growth from exponential phase to stationary, marked alteration takes place in the pattern of overall genome expression through modulation of both parts of the transcriptional and translational apparatus. In transcription, the sigma subunit with promoter recognition properties is replaced from the growth-related factor RpoD by the stationary-phase-specific factor RpoS. The unused RpoD is stored by binding with the anti-sigma factor Rsd. In translation, the functional 70S ribosome is converted to inactive 100S dimers through binding with the ribosome modulation factor (RMF). Up to the present time, the regulatory mechanisms of expression of these two critical proteins, Rsd and RMF, have remained totally unsolved. In this study, attempts were made to identify the whole set of transcription factors involved in transcription regulation of the rsd and rmf genes using the newly developed promoter-specific transcription factor (PS-TF) screening system. In the first screening, 74 candidate TFs with binding activity to both of the rsd and rmf promoters were selected from a total of 194 purified TFs. After 6 cycles of screening, we selected 5 stress response TFs, ArcA, McbR, RcdA, SdiA, and SlyA, for detailed analysis in vitro and in vivo of their regulatory roles. Results indicated that both rsd and rmf promoters are repressed by ArcA and activated by McbR, RcdA, SdiA, and SlyA. We propose the involvement of a number of TFs in simultaneous and coordinated regulation of the transcriptional and translational apparatus. By using genomic SELEX (gSELEX) screening, each of the five TFs was found to regulate not only the rsd and rmf genes but also a variety of genes for growth and survival. IMPORTANCE During the growth transition of E. coli from exponential phase to stationary, the genome expression pattern is altered markedly. For this alteration, the transcription apparatus is altered by binding of anti-sigma factor Rsd to the RpoD sigma factor for sigma factor replacement, while the translation machinery is modulated by binding of RMF to 70S ribosome to form inactive ribosome dimer. Using the PS-TF screening system, a number of TFs were found to bind to both the rsd and rmf promoters, of which the regulatory roles of 5 representative TFs (one repressor ArcA and the four activators McbR, RcdA, SdiA, and SlyA) were analyzed in detail. The results altogether indicated the involvement of a common set of TFs, each sensing a specific environmental condition, in coordinated hibernation of the transcriptional and translational apparatus for adaptation and survival under stress conditions.

The optimal tomotherapy treatment planning parameters for extremity soft tissue sarcomas.

BACKGROUND AND PURPOSE: To determine the optimum combination of treatment parameters between pitch, field width (FW) and modulation factor (MF) for extremity sarcomas in tomotherapy. MATERIALS AND METHODS: Six patients previously treated for extremity sarcomas (3 arms and 3 legs) with tomotherapy were included in this study. 288 treatment plans were recalculated, corresponding to all combinations between 2 FW (2.5 and 5 cm), 4 MF (1.5, 2, 2.5 and 3) and 6 pitches (0.215, 0.287, 0.43 and 3 off-axis pitches). The treatment parameters (MF, FW or pitch) are modified between each plan, and the calculation is relaunched for 400 iterations, without modifying the optimisation constraints of the plan under which the patient has been treated. RESULTS: We suggest eliminating the 0.43 pitch and never combining a 0.215 pitch with an MF ≤ 2. We also do not recommend using an MF = 1.5 unless treatment time is an absolute priority over plan quality. We did not see any advantage in using Chen off-axis pitches, except for targets far from the axis (>15 cm) treated with a high pitch. A combination of MF = 2/FW = 5 cm/pitch = 0.287 gives plans of acceptable quality, combined with reduced treatment times. These conclusions are true only for extremity sarcomas treated in 2 Gy/fraction. CONCLUSIONS: We have shown that the choice of pitch/MF/FW combination is crucial for the treatment of extremity sarcomas in tomotherapy: some produce good dosimetric quality with a reduced irradiation time, while others may increase the time without improving the quality.