Search

BACKGROUND: PET (positron emission tomography) and CSF (cerebrospinal fluid) provide the “ATN” (Amyloid, Tau, Neurodegeneration) classification and play an essential role in early and differential diagnosis of Alzheimer’s disease (AD). OBJECTIVE: Biomarkers were evaluated in a Japanese multicenter study on cognitively unimpaired subjects (CU) and early (E) and late (L) mild cognitive impairment (MCI) patients. MEASUREMENTS: A total of 38 (26 CU, 7 EMCI, 5 LMCI) subjects with the age of 65-84 were enrolled. Amyloid-PET and FDG-PET as well as structural MRI were acquired on all of them, with an additional tau-PET with 18F-flortaucipir on 15 and CSF measurement of Aβ1-42, P-tau, and T-tau on 18 subjects. Positivity of amyloid and tau was determined based on the positive result of either PET or CSF. RESULTS: The amyloid positivity was 13/38, with discordance between PET and CSF in 6/18. Cortical tau deposition quantified with PET was significantly correlated with CSF P-tau, in spite of discordance in the binary positivity between visual PET interpretation and CSF P-tau in 5/8 (PET-/CSF+). Tau was positive in 7/9 amyloid positive and 8/16 amyloid negative subjects who underwent tau measurement, respectively. Overall, a large number of subjects presented quantitative measures and/or visual read that are close to the borderline of binary positivity, which caused, at least partly, the discordance between PET and CSF in amyloid and/or tau. Nine subjects presented either tau or FDG-PET positive while amyloid was negative, suggesting the possibility of non-AD disorders. CONCLUSION: Positivity rate of amyloid and tau, together with their relationship, was consistent with previous reports. Multicenter study on subjects with very mild or no cognitive impairment may need refining the positivity criteria and cutoff level as well as strict quality control of the measurements.

In the research sponsored by the National Institute for Land and Infrastructure Management, the development of new design methods for composite girders has been discussed. In this method, various characteristics of the plastic design of composite girders were taken into account. In order to investigate the effects of the bonding at the steel-concrete interface, the three-point bending test was conducted on two composite girders with the same dimension. A detaching agent was applied to the interface between the concrete slab and the steel upper flange to eliminate the bonding. According to the test results obtained in this study, there was little effect of bonding on the maximum strength, and both test specimens exceeded the strength corresponding to the theoretical total plastic moment. Both test specimens with and without bonding reached the ultimate state due to the collapse of concrete of the RC slab.

Background Blood pressure (BP) variability has reportedly been a risk factor for various clinical events. To clarify the influence of BP visit‐to‐visit variability on adverse events in patients with nonvalvular atrial fibrillation, a post hoc analysis of the J‐RHYTHM Registry was performed. Methods and Results Of 7406 outpatients with nonvalvular atrial fibrillation from 158 institutions, 7226 (age, 69.7±9.9 years; men, 70.7%), in whom BP was measured 4 times or more (14.6±5.0 times) during the 2‐year follow‐up period or until occurrence of an event, constituted the study group. SD and coefficient of variation of BP values were calculated as BP variability. Thromboembolism, major hemorrhage, and all‐cause death occurred in 110 (1.5%), 121 (1.7%), and 168 (2.3%) patients, respectively. When patients were divided into quartiles of systolic BP‐SD (P =0.015 for thromboembolism; HR, 2.60, 95% CI, 1.36–4.97, P =0.004 for major hemorrhage; and HR, 1.85, 95% CI, 1.11–3.07, P =0.018 for all‐cause death) after adjusting for components of the CHA 2 DS 2 ‐VASc score, warfarin and antiplatelet use, atrial fibrillation type, BP measurement times, and others. These findings were consistent when BP‐coefficient of variation was used instead of BP‐SD. Conclusions Systolic BP visit‐to‐visit variability was significantly associated with all adverse events in patients with nonvalvular atrial fibrillation. Further studies are needed to clarify the causality between BP variability and adverse outcomes in patients with nonvalvular atrial fibrillation. Registration URL: https://www.umin.ac.jp/ctr/ ; Unique Identifier: UMIN000001569.

Background To clarify the influence of hypertension and blood pressure ( BP ) control on thromboembolism and major hemorrhage in patients with nonvalvular atrial fibrillation, a post hoc analysis of the J‐ RHYTHM Registry was performed. Methods and Results A consecutive series of outpatients with atrial fibrillation was enrolled from 158 institutions. Of 7937 patients, 7406 with nonvalvular atrial fibrillation (70.8% men, 69.8±10.0 years) were followed for 2 years or until an event occurred. Hypertension was defined as a systolic BP ≥140 mm Hg, a diastolic BP ≥90 mm Hg, a history of hypertension, and/or antihypertensive drug use. Hypertension was an independent risk factor for major hemorrhage (hazard ratio 1.52, 95% CI 1.05–2.21, P =0.027) but not for thromboembolism (hazard ratio 1.05, 95% CI 0.73–1.52, P =0.787). When patients were divided into quartiles according to their systolic BP at the time closest to the event or at the end of follow‐up (Q1, CI 1.75–4.74, P CI 1.02–2.53, P =0.041) after adjustment for components of CHA 2 DS 2 ‐ VAS c score, warfarin use, and antiplatelet use. A systolic BP of ≥136 mm Hg was an independent risk factor for thromboembolism and major hemorrhage. Conclusions BP control appears to be more important than a history of hypertension and baseline BP values at preventing thromboembolism and major hemorrhage in patients with nonvalvular atrial fibrillation. Clinical Trial Registration URL : http://www.umin.ac.jp/ctr . Unique identifier: UMIN 000001569.

Background and purpose To investigate a weighted four-dimensional (W-4D) treatment planning strategy based on the greater clinical advantage of the conformal over the intensity-modulated technique in lung stereotactic body radiotherapy (SBRT). Material and methods Two planning strategies (individual-phase 4D [IP-4D] and W-4D) were evaluated in eighteen lung SBRT patients. The IP-4D plan can deliver a constant fluence during whole respiratory phases. The W-4D plan's key concept was to escalate (or reduce) fluence using a 4D optimization algorithm when the tumour target was out-of-line (or in-line) with an organ-at-risk. The fluence was converted to a dynamic multi-leaf collimator leaf sequence for deliverable 4D irradiation. Results In all patients, the W-4D plan enabled planning tumour volume conformity comparable to the IP-4D plan. The W-4D plan yielded a significantly lower maximum dose than the IP-4D plan for the spinal cord (−11%; p p p = 0.01) and stomach (−23%; p = 0.07), and a lower mean dose to liver (−19%; p = 0.18) while maintaining the mean dose to lung (−1%; p = 0.23). Conclusions W-4D is a robust, practical planning approach that achieves significant dose sparing relative to non-time-resolved tracking; it may be of greater clinical benefit in radiotherapy than the spatially intensity-modulated 4D approach.

This prospective, open-label, multicentre study examined the efficacy and safety of rapidly (overnight) or slowly (after 2 weeks of concomitant usage) switching patients with Parkinson's disease (PD) from conventional ergot dopamine agonists (DAs) to the non-ergot DA, pramipexole. Fifty-nine early-to-advanced PD patients with motor symptoms that were inadequately controlled by ergot DAs were enrolled. Patients were switched from ergot derivatives to pramipexole and evaluated every 2 weeks for 12 weeks by Hoehn and Yahr staging, Unified Parkinson's Disease Rating Scale (UPDRS) and a modified Epworth Sleepiness Scale (mESS). The UPDRS III subscores and total UPDRS scores significantly improved, independent of switching method. Adverse events, all of which were mild, occurred in 29.2% of patients. No sudden onset of excessive daytime sleepiness or significant worsening in mESS was seen. Switching patients with PD from ergot DA to pramipexole, using either a slow or rapid switching method, appeared to be well tolerated and effective, although further dose adjustment may be necessary in some patients after the switch.

In the late stages of nuclear burning for massive stars ($M>8~M_{\sun}$), the production of neutrino-antineutrino pairs through various processes becomes the dominant stellar cooling mechanism. As the star evolves, the energy of these neutrinos increases and in the days preceding the supernova a significant fraction of emitted electron anti-neutrinos exceeds the energy threshold for inverse beta decay on free hydrogen. This is the golden channel for liquid scintillator detectors because the coincidence signature allows for significant reductions in background signals. We find that the kiloton-scale liquid scintillator detector KamLAND can detect these pre-supernova neutrinos from a star with a mass of $25~M_{\sun}$ at a distance less than 690~pc with 3$\sigma$ significance before the supernova. This limit is dependent on the neutrino mass ordering and background levels. KamLAND takes data continuously and can provide a supernova alert to the community., Comment: 19 pages, 6 figures, 1 table

The timing of glacial advances, periglacial phenomena, and the ages of two marker tephras in northern Hokkaido were estimated by OSL dating. It appears that the glacier of Yamunai 2 stage on Rishiri Island expanded between 24 and 15 ka. In northern Hokkaido, OSL ages indicate ice wedge formation during the period 24–18 ka. These results indicate that both the glacial advance and the development of ice wedges were synchronous phenomena relating to the Last Glacial Maximum.

Recent developments in radiation therapy have been focused on applications of charged particles, especially—protons. Proton therapy can allow higher dose conformality compared to conventional radiation therapy. Dose calculations have an integral role in the successful application of proton therapy. Over the years several dose calculation methods have been proposed in proton therapy. A common characteristic of all these methods is their extensive computational burden. One way to ameliorate that issue is the parallelization of the algorithm. Graphics processing units (GPUs) have recently been employed to accelerate the proton dose calculation process. Pencil-beam dose calculation algorithms for proton therapy have been widely utilized in clinical routine for treatment planning purposes in most clinical settings, due to their simplicity of calculation scheme and acceptable accuracy. In the current study a GPU-based pencil beam algorithm for dose calculations with protons is proposed. The studies indicated a maximum speedup factor of \(\sim \)127 in a homogeneous phantom.

We present a search for the proton decay mode p→ν¯K+ based on an exposure of 8.97 kton-years in the KamLAND experiment. The liquid scintillator detector is sensitive to successive signals from p→ν¯K+ with unique kinematics, which allow us to achieve a detection efficiency of 44%, higher than previous searches in water Cherenkov detectors. We find no evidence of proton decays for this mode. The expected background, which is dominated by atmospheric neutrinos, is 0.9±0.2 events. The nonbackground-subtracted limit on the partial proton lifetime is τ/B(p→ν¯K+)>5.4×1032 years at 90% C.L.

Four kinds of film dosimeters well-characterized for low linear energy transfer (LET) radiations were applied to 3–45 MeV/u ions. The dose–responses relative to those for low LET radiations are almost one at a stopping power of about 10 MeV/(mg/cm 2 ) and gradually become smaller with an increase in the stopping power. The overall uncertainty in ion beam dosimetry using these characterized dosimeters is better than ±5% (1 σ ) including uncertainty in fluence measurement (±2%). Lateral- and depth-dose profile measurements were made using one of the dosimeters (Gafchromic) with a spatial resolution of better than 1 and 10 μm, respectively.

KamLAND-Zen reports on a preliminary search for neutrinoless double-beta decay with 136Xe based on 114.8 live-days after the purification of the xenon loaded liquid scintillator. In this data, the problematic 110mAg background peak identified in previous searches is reduced by more than a factor of 10. By combining the KamLAND-Zen pre- and post-purification data, we obtain a preliminary lower limit on the 0νββ decay half-life of T 0ν 1/2 > 2.6 × 1025 yr at 90% C.L. The search sensitivity will be enhanced with additional low background data after the purification. Prospects for further improvements with future KamLAND-Zen upgrades are also presented.

A search for double-beta decays of 136Xe to excited states of 136Ba has been performed with the first phase data set of the KamLAND-Zen experiment. The 0+1, 2+1 and 2+2 transitions of 0{\nu}\{beta}\{beta} decay were evaluated in an exposure of 89.5kg-yr of 136Xe, while the same transitions of 2{\nu}\{beta}\{beta} decay were evaluated in an exposure of 61.8kg-yr. No excess over background was found for all decay modes. The lower half-life limits of the 2+1 state transitions of 0{\nu}\{beta}\{beta} and 2{\nu}\{beta}\{beta} decay were improved to T(0{\nu}, 0+ \rightarrow 2+) > 2.6\times10^25 yr and T(2{\nu}, 0+ \rightarrow 2+) > 4.6\times10^23 yr (90% C.L.), respectively. We report on the first experimental lower half-life limits for the transitions to the 0+1 state of 136Xe for 0{\nu}\{beta}\{beta} and 2{\nu}\{beta}\{beta} decay. They are T (0{\nu}, 0+ \rightarrow 0+) > 2.4\times10^25 yr and T(2{\nu}, 0+ \rightarrow 0+) > 8.3\times10^23 yr (90% C.L.). The transitions to the 2+2 states are also evaluated for the first time to be T(0{\nu}, 0+ \rightarrow 2+) > 2.6\times10^25 yr and T(2{\nu}, 0+ \rightarrow 2+) > 9.0\times10^23 yr (90% C.L.). These results are compared to recent theoretical predictions., Comment: 16 pages, 4 figures. Published in Nuclear Physics A

We search for electron anti-neutrinos ($\overline{\nu}_e$) from long and short-duration gamma-ray bursts~(GRBs) using data taken by the KamLAND detector from August 2002 to June 2013. No statistically significant excess over the background level is found. We place the tightest upper limits on $\overline{\nu}_e$ fluence from GRBs below 7 MeV and place first constraints on the relation between $\overline{\nu}_e$ luminosity and effective temperature., Comment: 16 pages and 5 figures

Light chain shifting is a phenomenon that occurs in certain human antibody-producing plasma B cells which, when stimulated with concanavalin A (Con A), shift production of the original light chain to new light chains. Here we investigated the effect of Con A stimulation on these light chain shift-inducible cells. Analysis of transcripts and VJ-coding joints for new light chains revealed that a leaky amount of secondary VλJλ rearrangement occurs spontaneously, without Con A stimulation, and that Con A stimulation markedly increases VJ-coding joints and transcripts for new light chains. It was also shown that new light chain producers, which have carried out secondary rearrangement, do not further rearrange their light chain genes, even when stimulated with Con A. Recombination-activating gene (RAG) products and Vλ germline transcription were constitutively expressed in these cell lines and their expression levels were not affected by Con A stimulation. These results suggest that Con A stimulation enhanced secondary VλJλ rearrangement, but this was not a result of the up-regulation of RAG expression and Vλ germline transcription, which are believed to be sufficient for the process of VλJλ rearrangement.

The uncertainties in 60Co gamma-ray dosimetry at JAERI have been estimated by reviewing irradiation and calibration procedures. The uncertainty in dose delivered by the JAERI calibration system has been estimated to be 2.2% (2σ) and the uncertainty in dose measurement using JAERI alanine/ESR transfer dosimeters has been estimated to be 3.4% (2σ). A two-way dose intercomparison study between NPL and JAERI employing alanine-PS, alanine-paraffin, and dichromate dosimeters as transfer dosimeters was performed to confirm the estimated uncertainty over the dose range 1–50 kGy. Dose intercomparison results using both alanine and dichromate dosimeters show agreement within about 2%, which gives confidence in the estimated uncertainty in 60Co gamma-ray dosimetry at JAERI.

Purpose: To evaluate the functional planning using CT-pulmonary ventilation imaging for conformal SBRT. Methods: The CT-pulmonary ventilation image was generated using the Jacobian metric in the in-house program with the NiftyReg software package. Using the ventilation image, the normal lung was split into three lung regions for functionality (high, moderate and low). The anatomical plan (AP) and functional plan (FP) were made for ten lung SBRT patients. For the AP, the beam angles were optimized with the dose-volume constraints for the normal lung sparing and the PTV coverage. For the FP, the gantry angles were also optimized with the additional constraint for high functional lung. The MLC aperture shapes were adjusted to the PTV with the additional 5 mm margin. The dosimetric parameters for PTV, the functional volumes, spinal cord and so on were compared in both plans. Results: Compared to the AP, the FP showed better dose sparing for high- and moderate-functional lungs with similar PTV coverage while not taking care of the low functional lung (High:−12.9±9.26% Moderate: −2.0±7.09%, Low: +4.1±12.2%). For the other normal organs, the FP and AP showed similar dose sparing in the eight patients. However, the FP showed that the maximum doses for spinal cordmore » were increased with the significant increment of 16.4Gy and 21.0Gy in other two patients, respectively. Because the beam direction optimizer chose the unexpected directions passing through the spinal cord. Conclusion: Even the functional conformal SBRT can selectively reduce high- and moderatefunctional lung while keeping the PTV coverage. However, it would be careful that the optimizer would choose unexpected beam angles and the dose sparing for the other normal organs can be worse. Therefore, the planner needs to control the dose-volume constraints and also limit the beam angles in order to achieve the expected dose sparing and coverage.« less

A Faraday cup was fabricated for measuring the beam current of a few tens MeV/amu ion beams of the TIARA AVF cyclotron. It has been applied as a beam monitor for studying the characteristics of film dosimeters that are well-established for high doses of 60 Co γ-rays and 1 to 10 MeV electrons. A total absorption calorimeter designed to measure energy fluence has also been tested for estimating the uncertainty in fluence measurement of 5–20 MeV/amu ion beams, by simultaneous use of the calorimeter and the Faraday cup in a broad uniform fluence field. The estimated fluence was evaluated on the basis of nominal particle energy values derived from the cyclotron acceleration parameters. The average ratio of the measured fluence values to the estimated values is 1.024, and the average precision is within ±2% at a 68% confidence level, for most of the ion beams with a range of kinetic energy per nucleon, 5–20 MeV/amu, at an integrated charge above 5 nC/cm 2 .

The irradiation temperature dependence of the 60 Co gamma-ray dose response of a silver-dichromate dosimeter was studied to verify temperature coefficients over 5–60°C, using both low and high range standard-type dosimeters. The temperature coefficients in the temperature range 25–60°C are estimated to be −0.20 and −0.26%/°C respectively at doses 2–10 kGy and 10–50 kGy, although there is a slight tendency of dose dependence. The coefficients covering temperatures of 25–50°C estimated to low and high dose ranges are respectively −0.20 and −0.23%/°C which lead us to confirm the previous data including the ASTM Standards E1401-96, 1997 . The effect of temperature during spectrophotometry analysis on molar extinction coefficients was not appreciably observed in the temperature range 5–50°C.

The purpose of this study was to explore the variables related to paternal involvement in the caregiving of 6- to 8-year-old extremely low-birthweight (ELBW) children, specifically, sociodemographic factors related to the family or individual biological factors related to ELBW. Thirty-three children with a mean birthweight of 845.5 grams and a mean gestational age of 27.4 weeks participated in this research. Approximately 29% of their fathers were classified by the mothers as nonco-operative in overall child care. The paternal involvement in caregiving was related to the sociodemographic variables of the family; the co-operative fathers were proportionally more often from families where the child had no older female sibling(s) and/or grandparent(s), whereas the nonco-operative fathers were proportionally more often from families where the child had older female sibling(s) and/or grandparent(s). The individual perinatal risk variables and IQ, and the paternal variables (age, socioeconomic status) were not related to the paternal co-operativeness. Our sample mothers seemed to have raised their children in more difficult parenting and economic situations, and to have received proportionally more support from grandparent(s) than did typical Japanese mothers. The children's relationships with peers differed between the paternal co-operative and nonco-operative groups; there were proportionally more children from the nonco-operative group who preferred to play alone than to play with peer(s) at the ages of 3-5 years. Thus, scarce paternal involvement in the process of caregiving appeared to influence the children's sociability.

Temperature effects on dose responses of undyed and dyed polymethylmethacrylate (PMMA)_dosimeters were studied at doses of 2 and 25 kGy under irradiation temperatures from −196°C to +45°C. At 25 kGy, Radix RN15 has linear dependence with a coefficient of +0.15%/°C and +0.25%/°C for irradiation temperature below and above −15°C respectively, and Red 4034 and Amber 3042 have smaller dependence in this temperature range, although Red 4034 has relatively high responses at −196°C and −78°C. At a dose of 2 kGy, dose response of Amber 3042 increases nearly linearly with temperature above −78°C with a coefficient of about 0.5%/°C. The dose response of Gammachrome YR below −78°C is almost 30% higher than that at 20°C and decreases with increasing temperature above −78°C with temperature coefficient of −0.3%/°C.

The permeability, temperature and morphologic changes of the wall of the root canal induced by Nd:YAG, CO2 and argon lasers were studied. The changes were evaluated according to the presence or absence of a smear layer. Root canals of 140 human single-rooted teeth were enlarged using a step-back technique. Permeability was evaluated by the extent of methylene blue dye penetration into the tubules. Temperature changes were measured using a thermovision system, and morphological changes were evaluated by scanning electron microscopy. Laser energy was delivered into the canal by means of a flexible optical fibre or metal tip. There were statistically significant differences in permeability between lased groups with and without a smear layer in the cervical third of the root canal following lasing. In the middle third of the root canal, all three laser types induced permeability increases in groups with a smear layer. In the apical third, statistically significantly decreases in permeability were observed among CO2 laser and Nd:YAG compared with control group (P < 0.01). Rises in temperature ranged from a minimum of +10.1 degrees C (CO2 laser) to a maximum of +54.8 degrees C (argon laser). All three laser devices appeared capable of producing a glazed-like surface and craters.

A nummular headache is a headache that is characterized by pain localized to a small, circumscribed area of the head, typically measuring 2 to 6 cm in diameter in the absence of any lesion of the underlying structures.

Orientation effects during electron spin resonance (ESR) measurement are studied on alanine-polymer dosimeters prepared by different molding procedures (press-molding or extrusion), and also according to different shapes (rods with different lengths and thin-films). The variation in ESR signal amplitude was measured by rotating a dosimeter around the vertical mid-axis and at a right angle to the magnetic field in the ESR cavity, at a temperature of 22°C. Orientation effects for rod dosimeters with both molding procedures (press and extrusion), and with different lengths, were negligible. Thin-film dosimeters molded by extrusion show a pronounced orientation effect when the samples are cut into disks and positioned horizontally (parallel to the magnetic field) during readout in the ESR cavity. Orientation effects on the film dosimeters can be eliminated, however, when they are positioned vertically and parallel to the mid-axis of the ESR cavity.

Sumitomo Metal Industries, Ltd, has developed a new control system for the runout table cooling in the hot strip mill at Kashima Steel Works. The new features are an over-head water tank, pipe laminar headers via two pipes, spray cooling headers for thin strips, and a high performance process computer. This system operates with a model that precisely predicts the strip temperature. The system has increased the automatic operation ratio of the coiling temperature control, and has significantly improved the coiling temperature accuracy.

Purpose: CyberKnife irradiation is composed of tiny-size, multiple and intensity-modulated beams compared to conventional linacs. Few of the publications for Independent dose calculation verification for CyberKnife have been reported. In this study, we evaluated the feasibility of independent dose verification for CyberKnife treatment as Secondary check. Methods: The followings were measured: test plans using some static and single beams, clinical plans in a phantom and using patient's CT. 75 patient plans were collected from several treatment sites of brain, lung, liver and bone. In the test plans and the phantom plans, a pinpoint ion-chamber measurement was performed to assess dose deviation for a treatment planning system (TPS) and an independent verification program of Simple MU Analysis (SMU). In the clinical plans, dose deviation between the SMU and the TPS was performed. Results: In test plan, the dose deviations were 3.3±4.5%, and 4.1±4.4% for the TPS and the SMU, respectively. In the phantom measurements for the clinical plans, the dose deviations were −0.2±3.6% for the TPS and −2.3±4.8% for the SMU. In the clinical plans using the patient's CT, the dose deviations were −3.0±2.1% (Mean±1SD). The systematic difference was partially derived from inverse square law and penumbra calculation. Conclusion: The independent dose calculation for CyberKnife shows −3.0±4.2% (Mean±2SD) and our study, the confidence limit was achieved within 5% of the tolerance level from AAPM task group 114 for non-IMRT treatment. Thus, it may be feasible to use independent dose calculation verification for CyberKnife treatment as the secondary check. This research is partially supported by Japan Agency for Medical Research and Development (AMED)

Purpose: For head and neck VMAT (HN-VMAT), variations of position and deformation of patient's shoulders is a concern to affect inaccuracy of dose distribution. It has been reported that the setup error of the shoulders was variable from 5 mm – 1 cm. The beams of the HN-VMAT pass through the shoulders. We assessed the impact of shoulder deformation to dose distribution for HN-VMAT. Methods: One HN-VMAT plan was generated using a patient's CT. The patient's CT was deformed using ImSimQA (Oncology Systems Limited, Shrewsbury, Shropshire, UK) to generate several patterns of the shoulders’ deformations when the right and left humeral heads were shifted with 3, 6, and 15 mm in the superior and inferior directions (SI), 3, 5, and 15 mm in the anterior and posterior directions (AP), and 5 and 15 mm in the right or left direction (LR). DVH comparison was performed in the different deformation patterns. The dosimetric parameters of D95% for CTV70Gy, CTV60Gy and CTV54Gy and dmax for Spinal cord were also measured. Gamma index evaluation (Criteria: 3%/2mm) was performed to exhibit clinically tolerable area in the comparison. Results: DVH comparison shows similar for all structures. As the comparison for the dosimetric parameters, the variations of D95% in the LR and AP were within 1%. There were larger variations in the SI than those in the other directions, however were within 1.5%. In gamma index evaluation, the small spots with higher gamma index values were appeared when the shift was 6 mm, however the pass ratio was 99.13%. Conclusion: HN-VMAT should be robust for shoulder deformation and geometric accuracy within 6 mm from patient's setup and image-guided radiotherapy may be clinically acceptable for target dose coverage or normal tissue dose sparing.

Purpose: To investigate the effect of the trajectory files from linear accelerator for Clarkson-based independent dose verification in IMRT and VMAT plans. Methods: A CT-based independent dose verification software (Simple MU Analysis: SMU, Triangle Products, Japan) with a Clarksonbased algorithm was modified to calculate dose using the trajectory log files. Eclipse with the three techniques of step and shoot (SS), sliding window (SW) and Rapid Arc (RA) was used as treatment planning system (TPS). In this study, clinically approved IMRT and VMAT plans for prostate and head and neck (HN) at two institutions were retrospectively analyzed to assess the dose deviation between DICOM-RT plan (PL) and trajectory log file (TJ). An additional analysis was performed to evaluate MLC error detection capability of SMU when the trajectory log files was modified by adding systematic errors (0.2, 0.5, 1.0 mm) and random errors (5, 10, 30 mm) to actual MLC position. Results: The dose deviations for prostate and HN in the two sites were 0.0% and 0.0% in SS, 0.1±0.0%, 0.1±0.1% in SW and 0.6±0.5%, 0.7±0.9% in RA, respectively. The MLC error detection capability shows the plans for HN IMRT were the most sensitive and 0.2 mm of systematic error affected 0.7% dose deviation on average. Effect of the MLC random error did not affect dose error. Conclusion: The use of trajectory log files including actual information of MLC location, gantry angle, etc should be more effective for an independent verification. The tolerance level for the secondary check using the trajectory file may be similar to that of the verification using DICOM-RT plan file. From the view of the resolution of MLC positional error detection, the secondary check could detect the MLC position error corresponding to the treatment sites and techniques. This research is partially supported by Japan Agency for Medical Research and Development (AMED)

Purpose: There have been several publications focusing on dose calculation in lung for a new dose calculation algorithm of Acuros XB (AXB). AXB could contribute to dose calculation for high-density media for bone and dental prosthesis rather than in lung. We compared the dosimetric performance of AXB, Adaptive Convolve (AC) in head and neck IMRT plans. Methods: In a phantom study, the difference in depth profile between AXB and AC was evaluated using Kodak EDR2 film sandwiched with tough water phantoms. 6 MV x-ray using the TrueBeam was irradiated. In a patient study, 20 head and neck IMRT plans had been clinically approved in Pinnacle3 and were transferred to Eclipse. Dose distribution was recalculated using AXB in Eclipse while maintaining AC-calculated monitor units and MLC sequence planned in Pinnacle. Subsequently, both the dose-volumetric data obtained using the two different calculation algorithms were compared. Results: The results in the phantom evaluation for the shallow area ahead of the build-up region shows over-dose for AXB and under-dose for AC, respectively. In the patient plans, AXB shows more hot spots especially around the high-density media than AC in terms of PTV (Max difference: 4.0%) and OAR (Max. difference: 1.9%). Compared to AC, there were larger dose deviations in steep dose gradient region and higher skin-dose. Conclusion: In head and neck IMRT plans, AXB and AC show different dosimetric performance for the regions inside the target volume around high-density media, steep dose gradient regions and skin-surface. There are limitations in skin-dose and complex anatomic condition using even inhomogeneous anthropomorphic phantom Thus, there is the potential for an increase of hot-spot in AXB, and an underestimation of dose in substance boundaries and skin regions in AC.

To investigate the effects of brown stem rot, a vascular disease of soybean (Glycine max) induced by Phialophora gregata, on the water relations of diseased plants, stems of greenhouse-grown plants of susceptible (Pride B216) and resistant (BSR 201) cultivars were injected with the pathogen at vegetative growth stage VI. Plants of both cultivars developed internal stem browning, but those of Pride B216 developed more severe symptoms of water stress (reduced leaf water potential and stem conductance). Inoculated plants of both cultivars also had reduced stem conductance and increased stomatal conductance and transpiration. Disease-related water stress can be attributed to the combined effects of reduced stem conductance and increased water loss resulting from increased stomatal conductance.

For microdosimetric calculations event-by-event Monte Carlo (MC) methods are considered the most accurate. The main shortcoming of those methods is the extensive requirement for computational time. In this work we present an event-by-event MC code of low projectile energy electron and proton tracks for accelerated microdosimetric MC simulations on a graphic processing unit (GPU). Additionally, a hybrid implementation scheme was realized by employing OpenMP and CUDA in such a way that both GPU and multi-core CPU were utilized simultaneously. The two implementation schemes have been tested and compared with the sequential single threaded MC code on the CPU. Performance comparison was established on the speed-up for a set of benchmarking cases of electron and proton tracks. A maximum speedup of 67.2 was achieved for the GPU-based MC code, while a further improvement of the speedup up to 20% was achieved for the hybrid approach. The results indicate the capability of our CPU-GPU implementation for accelerated MC microdosimetric calculations of both electron and proton tracks without loss of accuracy.

We attempted to improve antibody affinity by varying glycosylation on the light chain variable region. The human hybridoma line HB4C5 produces an antibody reactive to lung adenocarcinoma, which possess a N-glycosylated carbohydrate chain on the light chain hypervariable region. It has been shown that altering this carbohydrate structure can be accomplished by varying the level of N-acetylglucosamine in glucose free medium, a change in the carbohydrate chain could be induced which resulted in modifying antigen binding. By culturing the cells in media containing more than 20 mM N-acetylglucosamine, cells produced antibody with 10 fold improved affinity as compared with antibody produced in 20 mM glucose-containing medium. A newly induced light chain glycoform produced in the N-acetylglucosamine-containing medium was shown to be responsible for this antigen binding enhancement. Addition of glucose in the N-acetylglucosamine-containing media led to decreased antibody affinity and slightly inhibited production of a new light chain in a dose-dependent manner. Combination of 20 mM N-acetylglucosamine and 0.5 mM glucose gave a higher antibody production without the decrease of the antigen binding. These results indicate that optimization of N-glycosylation on the light chain, which leads to higher antigen binding, can be accomplished by adjusting a ratio of glucose and N-acetylglucosamine in the culture medium.

Human HB4C5 hybridoma cells produce a lung cancer-specific IgM human monoclonal antibody (mAb). HB4C5 human mAb cross-reacts with Candida cytochrome c (Cyt c) and carboxypeptidase (Cpase). Concanavalin A (ConA)-resistant variants of HB4C5 cells loss the original light chain followed by expression of various new light chains at a high incidence (light chain shifting) (Tachibana et al., 1996). HTD8 cells, one of the ConA-resistant variant subclones of HB4C5 cells, undergo the active light chain shifting and produce various sublines, each of which stably secretes new mAb consisting of a new light chain and a HB4C5 heavy chain. The new mAb exhibits altered antigen binding ability from that of the original antibody. We could expect that HTD8 cells can be used as ‘a light chain stem cell line’ to improve antigen binding ability and specificity of established human mAbs. A BD9D12 IgG human mAb recognizes lung cancer cells and cross-reacts with cytokeratin 8. Introduction of the heavy chain gene of BD9D12 mAb into HTD8 cells resulted in establishment of various sublines which secreted various kinds of hybrid antibodies consisting of different light chains derived from HTD8 subclones which underwent light chain shifting and a common IgG heavy chain derived from BD9D12. These hybrid antibodies exhibited different or improved reactivities to Cyt, Cpase, cytokeratin 8 and various cancer cells from those of parental mAb, demonstrating that light chain shifting can be applied to improve the affinity and specificity of human mAb.

To establish cheese as a dairy product with health benefits, we embarked on examining the multifunctional role of cheeses, especially in the field of cancer prevention. The current study was designed to investigate whether different types of commercial goat cheeses may possess antiproliferative activity, using an HL-60 human promyelocytic leukemia cell line as a cancer cell model. Among 11 cheese extracts tested at 500μg/mL, 6 (Crottin de Chavignol, Pouligny Saint-Pierre, Chabichou du Poitou, Valencay, Kavli, and Sainte-Maure de Touraine) resulted in a significant decrease of cell viability, which is consistent with a decrease in viable cell number. Compared with the half-maximal inhibitory concentration (IC(50)) value of individual cheeses in cellular proliferation assays, the Pouligny Saint-Pierre extract showed strong inhibition. Incubation of cells in the presence of Pouligny Saint-Pierre extract resulted in induction of cellular morphological changes and apoptotic DNA fragmentation as well as expression of the active form of caspase-3 protein. Based on the quantification of the ratio of free fatty acids to triglycerides in different cheese samples, a significant correlation was detected between lipolytic ripeness and IC(50) values for antiproliferative capacity tested in HL-60 cells. Collectively, these results support a potential role of highly lipolyzed goat cheeses in the prevention of leukemic cell proliferation.

A new alanine-polystyrene (PS) dosimeter prepared with simplified molding procedure and an automatic desk-top dose-reader of alanine dosimeter were developed for the purpose of routine use. Combination of these two allows us to apply a reliable alanine/ESR dosimetry system to routine dosimetric process control in industrial gamma radiation processing.