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Total body irradiation is an important part of the conditioning regimens frequently used to prepare patients for allogeneic hematopoietic stem cell transplantation (SCT). Volumetric-modulated arc therapy enabled total body irradiation (VMAT-TBI), an alternative to conventional TBI (cTBI), is a novel radiotherapy treatment technique that has been implemented and investigated in our institution. The purpose of this study is to (1) report our six-year clinical experience in terms of treatment planning strategy and delivery time and (2) evaluate the clinical outcomes and toxicities in our cohort of patients treated with VMAT-TBI. This is a retrospective single center study. Forty-four patients at our institution received VMAT-TBI and chemotherapy conditioning followed by allogeneic SCT between 2014 and 2020. Thirty-two patients (73%) received standard-dose TBI (12-13.2 Gy in 6-8 fractions twice daily), whereas 12 (27%) received low-dose TBI (2-4 Gy in one fraction). Treatment planning, delivery, and treatment outcome data including overall survival (OS), relapse-free survival (RFS), and toxicities were analyzed. The developed VMAT-TBI planning strategy consistently generated plans satisfying our dose constraints, with planning target volume coverage90%, mean lung dose ∼50% to 75% of prescription dose, and minimal hotspots in critical organs. Most of the treatment deliveries were100 minutes (range 33-147, mean 72). The median follow-up was 26 months. At the last follow-up, 34 of 44 (77%) of patients were alive, with 1- and 2-year OS of 90% and 79% and RFS of 88% and 71%, respectively. The most common grade 3+ toxicities observed were mucositis (31 patients [71%]) and nephrotoxicity (6 patients [13%]), both of which were deemed multifactorial in cause. Four patients (9%) in standard-dose cohort developed grade 3+ pneumonitis, with 3 cases in the setting of documented respiratory infection and only 1 (2%) deemed likely related to radiation alone. VMAT-TBI provides a safe alternative to cTBI. The dose modulation capability of VMAT-TBI may lead to new treatment strategies, such as simultaneous boost and further critical organ sparing, for better malignant cell eradication, immune suppression, and lower toxicities.

Purpose To improve the accuracy of liver tumor localization, this study tests a biomechanical modeling-guided liver cone-beam CT (CBCT) estimation (Bio-CBCT-est) technique, which generates new CBCTs by deforming a prior high-quality CT or CBCT image using deformation vector fields (DVFs). The DVFs can be used to propagate tumor contours from the prior image to new CBCTs for automatic 4D tumor localization. Methods/Materials To solve the DVFs, the Bio-CBCT-est technique employs an iterative scheme that alternates between intensity-driven 2D-3D deformation and biomechanical modeling-guided DVF regularization and optimization. The 2D-3D deformation step solves DVFs by matching digitally reconstructed radiographs of the 3D deformed prior image to 2D phase-sorted on-board projections according to imaging intensities. This step’s accuracy is limited at low-contrast intra-liver regions without sufficient intensity variations. To boost the DVF accuracy in these regions, we use the intensity-driven DVFs solved at higher-contrast liver boundaries to fine-tune the intra-liver DVFs by finite element analysis-based biomechanical modeling. We evaluated Bio-CBCT-est’s accuracy with seven liver cancer patient cases. For each patient, we simulated 4D cone-beam projections from 4D-CT images, and used these projections for Bio-CBCT-est based image estimations. After Bio-CBCT-est, the DVF-propagated liver tumor/cyst contours were quantitatively compared with the manual contours on the original 4D-CT ‘reference’ images, using the DICE similarity index, the center-of-mass-error (COME), the Hausdorff distance (HD) and the voxel-wise cross-correlation (CC) metrics. In addition to simulation, we also performed a preliminary study to qualitatively evaluate the Bio-CBCT-est technique via clinically acquired cone beam projections. A quantitative study using an in-house deformable liver phantom was also performed. Results Using 20 projections for image estimation, the average (±s.d.) DICE index increased from 0.48 ± 0.13 (by 2D-3D deformation) to 0.77 ± 0.08 (by Bio-CBCT-est), the average COME decreased from 7.7 ± 1.5 mm to 2.2 ± 1.2 mm, the average HD decreased from 10.6 ± 2.2 mm to 5.9 ± 2.0 mm, and the average CC increased from −0.004 ± 0.216 to 0.422 ± 0.206. The tumor/cyst trajectory solved by Bio-CBCT-est matched well with that manually obtained from 4D-CT reference images. Conclusions Bio-CBCT-est substantially improves the accuracy of 4D liver tumor localization via cone-beam projections and a biomechanical model.

Destination attributes represent the attractiveness of destinations that pull tourists to visit them. Destination marketers must understand what motivates tourists to choose certain destination attributes before they travel. Considering religious tourists plays an important aspect in influencing travel decisions, especially destination choices. For instance, the appearance of Islamic religious attributes in destinations can delight Muslim tourists and stimulate their satisfaction and loyalty. This study examines smart tourism city. In particular, it investigates the effects of Seoul’s destination attributes on Muslim tourists’ satisfaction and loyalty to South Korea. Results show that non-Islamic destination attributes (conventional attributes) have positive relationship with Muslim tourists’ satisfaction, and their satisfaction is positively related to their loyalty toward South Korea as a travel destination.

Cities and tourism entities invest massive resources into smart system initiatives as information technologies are a key factor for a city’s destination competitiveness. Moreover cities around the world are increasingly recognizing the smart tourism city concept and related strategies as means of optimizing sustainable environments. Particularly for cities facing emerging issues of residents’ negative perceptions towards tourism, smart tourism city empowers a city to rise to this challenge by creating urban spaces that residents and visitors can enjoy together. However, smart tourism city research initiatives still fail to address the full spectrum of related and potential developments. This study presents a conceptual approach to defining smart tourism city: the smart city and its components are defined and contrasted with smart tourism and its components. The resulting convergence—smart tourism city—is then examined in light of a number of pioneering examples of smart tourism cities and its vital roles in the age of sustainable development. The main purpose of this study is to show the interests of locals and tourists context and the roles of ‘smart’ government leadership to researchers and practitioners.

Background As there are few drugs for treating invasive aspergillosis, there is an urgent need for new antifungal agents. Enzymes involved in histone modification are possible antifungal drug targets. We set out to investigate whether genes whose products are involved in histone modifications influence the virulence of Aspergillus fumigatus (Af). Methods Genes whose products were likely involved in histone modification were deleted in strain Af293 using CRISPR-Cas9. Virulence was assessed in a triamcinolone-treated mouse model of invasive pulmonary aspergillosis. The extent of Af-induced damage to the A549 pulmonary epithelial cell line was determined by Cr51 release assay. Results Af genes were selected for investigation based on their homology to genes encoding known histone modifying proteins and their high expression level in vivo. The genes were predicted to encode members of the COMPASS histone methyltransferase complex (cclA/bre2, set2/Afu5g06000), the SAGA histone acetyltransferase complex (spt3, spt8), and the RPDL histone deacetylase complex (hosA). The ΔcclA and Δset2 mutants had significant growth defects on rich media and were not tested further. The Δspt3 and Δspt8 mutants grew normally and had mild conidiation defects. The ΔhosA mutant had wild-type (WT) growth and conidiation in vitro. Mice infected with the WT strain had 100% mortality within 9 days whereas mice infected the Δspt3, Δspt8, and ΔhosA mutants had only 40% mortality by 21 days. The ΔhosA mutant also had impaired capacity to damage pulmonary epithelial cells in vitro. Conclusion Ccla and Set2, components of the COMPASS complex, are required for normal growth in vitro. Spt3 and Spt8, members of the SAGA complex, are required for normal conidiation and virulence. HosA, part of the RPD3L complex, is necessary for maximal virulence and induction of host cell damage. Our results suggest that the HosA histone deacetylase may be a promising drug target for treating invasive aspergillosis. Disclosures All authors: No reported disclosures.

Purpose To assess the accuracy of current stereotactic body radiation therapy (SBRT) lung treatment planning methodologies on irregular breathing patterns, we have performed a systematic dosimetric evaluation in phantoms by utilizing maximum intensity projection (MIP) and average (AVG) images generated from four dimensional computed tomography (4DCT). Methods A custom built programmable lung phantom was used to simulate tumor motions due to various breathing patterns of patients. 4DCT scans were obtained in helical mode, and reconstructed AVG and MIP datasets were imported into the Pinnacle 8.0h treatment planning system. SBRT plans were generated and executed, and delivered doses were measured by radiochromic film for analysis. Results For targets moving regularly or irregularly within a small range (7.0±1.8mm, n =6), we observed good agreement between the measured and computed dose distributions. However, for targets moving irregularly with a larger range (20.8±2.6mm, n =4), the measured isodose lines were found to be shifted relative to the planned distribution, resulting in an under-dosing (over 10%) in a portion of the PTV. We further observed that the discrepancy between planned and measured dose distribution is due to the inaccurate representation of irregular target motion in the MIP images generated from 4DCT. Conclusions Caution should be used when planning from 4DCT images in the presence of large and irregular target motion. The inaccuracy inherent in 4DCT MIP and AVG images can be mitigated through the application of methodologies to reduce respiratory motion, such as abdominal compression, and through the use of volumetric image guidance (e.g., cone beam CT – CBCT) to assure precise targeting with minimal shifts.

To evaluate a moving blocker-based approach in estimating and correcting megavoltage (MV) and kilovoltage (kV) scatter contamination in kV cone-beam computed tomography (CBCT) acquired during volumetric modulated arc therapy (VMAT).During the concurrent CBCT/VMAT acquisition, a physical attenuator (i.e., "blocker") consisting of equally spaced lead strips was mounted and moved constantly between the CBCT source and patient. Both kV and MV scatter signals were estimated from the blocked region of the imaging panel, and interpolated into the unblocked region. A scatter corrected CBCT was then reconstructed from the unblocked projections after scatter subtraction using an iterative image reconstruction algorithm based on constraint optimization. Experimental studies were performed on a Catphan® phantom and an anthropomorphic pelvis phantom to demonstrate the feasibility of using a moving blocker for kV-MV scatter correction.Scatter induced cupping artifacts were substantially reduced in the moving blocker corrected CBCT images. Quantitatively, the root mean square error of Hounsfield units (HU) in seven density inserts of the Catphan phantom was reduced from 395 to 40.The proposed moving blocker strategy greatly improves the image quality of CBCT acquired with concurrent VMAT by reducing the kV-MV scatter induced HU inaccuracy and cupping artifacts.

summary Infection of barley leaves with powdery mildew results in an increase in the activity of acid invertase, concomitant with an accumulation of glucose, fructose and sucrose in the infected leaf; this increase is confined to the mesophyll cells. The rate of photosynthesis is controlled by different factors depending upon the experimental conditions under which it is measured. In saturating light and ambient CO2, photosynthesis is determined to a large extent by Rubisco whereas, in saturating light and saturating CO2. it is mainly determined by the rate of end-product synthesis (Pi-limitation). The rate of photosynthesis was measured under these conditions to reveal which of the partial processes was most affected in mildewed leaves. Under conditions of saturating light and ambient CO2, the rate of photosynthesis declined in mildewed leaves from 3 d after inoculation, suggesting that carboxylation had been affected. However, the maximum capacity for photosynthesis, measured at saturating CO2 and irradiance, increased in mildewed leaves for the first 3 d after infection and then decreased to below control values on days 5 and 7, suggesting that Pi was not limiting photosynthesis. This hypothesis was investigated by measuring changes in photosynthetic intermediates and in the activity and amount of key enzymes of the Calvin cycle as infection progressed. There was a decline in the activity of the stromal fru-1, 6-bisPase, Rubisco and NADP-GAPDH in mildewed leaves. These decreases were consistent with changes in the ratio of metabolites. As infection progressed, there was an increase in the ratio of Rul,5P2: PGA and triose-P: Rul,5P2, the first indicating a restriction in the carboxylation of CO2 and the second a restriction in the regeneration of Rul,5P2, The PGA: triose-P ratio was similar in control and mildewed leaves until day 7 when it decreased, suggesting that the reduction of PGA to triose-P was not affected by the disease. There was little evidence of Pi-limitation in the mildewed leaves; the amount of Pi in infected leaves was similar to controls, infected leaves showed no secondary oscillations during a transition from dark to light and there was a reduction in the amount of PGA in infected leaves. We suggest that the high concentration of carbohydrates, resulting from the increase in invertase activity, causes directly or indirectly a gradual down-regulation of the Calvin cycle leading to aft inhibition of photosynthesis.

Intact chloroplasts isolated from maize mesophyll have been used to investigate the relationship between the metabolic demand for ATP and the control of light-harvesting and electron transport. It was found that the rate of reduction of glycerate 3-phosphate can be either inhibited or stimulated by the addition of pyruvate, depending on their relative concentrations, pointing to optimisation of the ΔpH and the rate of electron transport. Pyruvate addition was associated with a stimulation of the phosphorylation of the light-harvesting chlorophyll protein complex, even when O2 evolution was stimulated. Under a variety of conditions, the level of phosphorylation was inversely correlated with the ΔpH. Emerson enhancement of the reduction of glycerate 3-phosphate is increased when pyruvate is added; the increased rate of O2 evolution brought about by far-red light is associated with an increase in the ΔpH. It is suggested that the ΔpH transmits the metabolic demand for ATP to the thylakoids, which respond by altering the relative rates of excitation of Photosystems I and II.

Purpose: To compare dosimetric data of patients treated for early-stage larynx cancer on Cyberknife and Linac IMRT. Methods: Nine patients were treated with Cyberknife to a dose of 45 Gy in 10 fractions of the involved hemilarynx. The prescription dose provided at least 95% of PTV coverage. After Cyberknife treatment, the CT images and contours were sent to Pinnacle treatment planning system for IMRT planning on a regular SBRT linac with same dose prescription and constrains. Dose to target and normal tissue, including the arytenoids, cord, carotid arteries, thyroid, and skin, were analyzed using dose volume histograms. Results: For Cyberknife plan, the conformity indices are within 1.11–1.33. The average dose to the contralateral arytenoids for Cyberknife plans was 28.9±6.5Gy), which is lower than the same mean dose for IMRT plans (34.0±5.2 Gy). The average maximum dose to the ipsilateral and contralateral carotid artery were 20.6 ±9.1 Gy and 10.2±6.0 Gy respectively for Cybeknife comparing with 22.1±8.0 Gy and 12.0±5.1 Gy for IMRT. The mean dose to the thyroid was 3.6±2.2 Gy for Cyberknife and 3.4±2.4 Gy for IMRT. As shown in DVH, the Cyberknife can deliver less dose to the normal tissue which is close to target area comparing with IMRT Plans. However, IMRT plan’s can give more sparing for the critical organs which is far away from the target area. Conclusion: We have compared the dosimetric parameters of Cyberknife and linac IMRT plans for patients with early-stage larynx cancer. Both Cyberknife and IMRT plans can achieve conformal dose distribution to the target area. Cyberknife was able to reduce normal tissue dose in high doses region while IMRT plans can reduce the dose of the normal tissue at the low dose region. These dosimetric parameters can be used to guide future prospective protocols using SBRT for larynx cancer.

Rusts and powdery mildews are biotrophic fungal pathogens which infect a wide variety of economically important plants. The powdery mildews are ectoparasites forming dense white mycelia on the leaf surface, with haustoria in epidermal cells. In the early stages of infection the nutrient fluxes characteristic of an uninfected plant may be sufficient to sustain fungal growth. However, as the mass of fungus increases a redirection of host assimilates to the pathogen occurs. This is accompanied by a number of other changes; in some host/pathogen interactions gross photosynthesis (per unit chlorophyll) may be enhanced initially (1), however, in most systems net photosynthesis then decreases and chlorophyll is lost from the tissue as the disease progresses (2).

Exposure of higher plants to irradiances in excess of those which can be dissipated by photochemistry or other mechanisms causes loss of photosynthetic performance (1). The tendency for this process (photoinhibition) is increased if the light intensity is in excess of that in which the plants are grown, if the CO2 level is lowered, if the temperature is decreased or if other stresses such as chilling or water stress are superimposed (2), suggesting that photoinhibition is a major negative factor in plant productivity even when irradiance is moderate (3). Studies of photoinhibition have so far used leaves and isolated chloroplasts. Here we describe photoinhibition in isolated protoplasts with a view to combining the presence of a more complete and stable metabolic system with the advantages of in vitro manipulation.

Upon illumination of leaves, the yield of fluorescence from chlorophyll decreases from a maximum (P) reached within ls to a steady state (T) several minutes later. During the PT quenching a series of transients are observed, a characteristic induction curve being described as PS1M1S2M2...SnMnT e.g. (Quick & Horton, these proceedings). Events occuring during the first few seconds are likely to reflect electron transfer and photophosphorylation only, whereas slower events are increasingly influenced by the onset of photosynthetic carbon assimilation. The yield of fluorescence under physiological conditions is affected by two major quenching processes, the oxidation state of O, (qO) and the trans-thylakoid ΔpH (qe). Before fluorescence measurement can be used to provide a non-intrusive assay of photosynthesis a clearer understanding is required of the interaction between qO and qe and their relationship to rates of electron transfer, ATP turnover and carbon assimilation. It is the aim of this study to provide in vitro simulation. of the mechanism and resultant fluorescence transients observable in vivo. For this we have used the reconstituted chloroplast system described by Lilley and Walker (1976). This system consists of thylakoids to which are added cofactors such as ferredoxin, ADP and NADP, and a stromal extract.

To determine the role of ethylene during tomato (Lycopersicon esculentum Mill. cv. Ailsa Craig} leaf senescence, transgenic ACC oxidase antisense plants were analysed. Northern analysis of wild-type plants indicated that ACC oxidase mRNA accumulation normally begins in pre-senescent green leaves but was severely reduced in the antisense plants. Although the levels of ethylene evolved by wild-type and transgenic leaves increased during the progression of senescence, levels were extremely low in transgenic leaves. Leaf senescence, as assessed by colour change from green to yellow, was clearly delayed by 10-14 days in the antisense plants when compared with wild-type plants. Northern analysis of the photosynthesis-associated genes, cab and rbcS, indicated that levels of the corresponding mRNAs were higher in transgenic leaves which were not yet senescing compared with senescing wild-type leaves of exactly the same age. Northern analysis using probes for tomato fruit ripening-related genes expressed during leaf senescence indicated that once senescence was initiated the expression pattern of these mRNAs was similar in transgenic and wildtype leaves. In the anticense plants chlorophyll levels, photosynthetic capacity and chlorophyll fluorescence were higher when compared with senescing wild-type plants of the same age. Photosynthetic capacity and the quantum efficiency of photosystem II were maintained for longer in the transformed plants at values close to those observed in wild-type leaves prior to the visible onset of senescence. These results indicate that inhibiting ACC oxidase expression and ethylene synthesis results in delayed leaf senes