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D Yan

Publications and source records attributed to D Yan.

At least 91 records · Page 5Linked to original sources

Invariant U2 RNA sequences bordering the branchpoint recognition region are essential for interaction with yeast SF3a and SF3b subunits.

U2 small nuclear RNA (snRNA) contains a sequence (GUAGUA) that pairs with the intron branchpoint during splicing. This sequence is contained within a longer invariant sequence of unknown secondary structure and function that extends between U2 and I and stem IIa. A part of this region has been proposed to pair with U6 in a structure called helix III. We made mutations to test the function of these nucleotides in yeast U2 snRNA. Most single base changes cause no obvious growth defects; however, several single and double mutations are lethal or conditional lethal and cause a block before the first step of splicing. We used U6 compensatory mutations to assess the contribution of helix III and found that if it forms, helix III is dispensable for splicing in Saccharomyces cerevisiae. On the other hand, mutations in known protein components of the splicing apparatus suppress or enhance the phenotypes of mutations within the invariant sequence that connect the branchpoint recognition sequence to stem IIa. Lethal mutations in the region are suppressed by Cus1-54p, a mutant yeast splicing factor homologous to a mammalian SF3b subunit. Synthetic lethal interactions show that this region collaborates with the DEAD-box protein Prp5p and the yeast SF3a subunits Prp9p, Prp11p, and Prp21p. Together, the data show that the highly conserved RNA element downstream of the branchpoint recognition sequence of U2 snRNA in yeast cells functions primarily with the proteins that make up SF3 rather than with U6 snRNA.

Base Sequence↗

Dosimetric evaluation of the conformation of the multileaf collimator to irregularly shaped fields.

PURPOSE: The goal of this study was to evaluate the dosimetric characteristics of geometric MLC prescription strategies and compare them to those of conventional shielding block. METHODS AND MATERIALS: Circular fields, square fields, and 12 irregular fields for patients with cancer of the head and neck, lung, and pelvis were included in this study. All fields were shaped using the MLC and conventional blocks. A geometric criterion was defined as the amount of area discrepancy between the MLC and the prescription outline. The "least area discrepancy" (LAD) of the MLC conformation was searched by selecting the collimator angle, meanwhile keeping a preselected position along the width of the leaf into the prescribed field. Five LAD conventions were studied. These included the LAD-0, LAD-1/3, LAD-1/2, and LAD-2/3 that inserted the leaves at the 0, 1/3, 1/2, and 2/3 of the leaf end into the prescription field, respectively. In addition, the LAD optimization was applied to the transecting (TRN) approach for leaf conformation that prescribed an equal area of overblocking and underblocking under each leaf. Film dosimetry was performed in a 20 cm polystyrene phantom at 10 cm depth 100 cm from source to axis distance (SAD) for both 6 and 18 MV photons with each of the above MLC conformations and conventional blocks. The field penumbra width, defined as the mean of the separation between the 20% and 80% isodose lines along the normal of the prescription field edge, was calculated using both the MLC and conventional block film dosimetry and compared. In a similar way, the d20 is defined as the mean separation between the 20% isodose line and the prescription field edge, and the d80 is defined as the mean separation between the 80% isodose line and the prescription field edge. RESULTS: The field penumbra width for all MLC conventions was approximately 2 mm larger than that of the conventional block. However, there was a larger variation of the separation distribution in the penumbra region of the irregular fields for the MLC, which had a standard deviation of 1 mm (a factor of 5 larger than the conventional block). The dosimetry for the circular fields showed that the LAD-TRN, LAD-1/2, and LAD-1/3 approximated the conventional blocking well in terms of d20 and d80; however, no single convention produced the best conformation for both measures. The dosimetric result of the patient treatment fields was similar for all sites. The LAD-1/3, LAD-1/2, and LAD-TRN strategies conformed to within 1 to 1.5 mm of the d80 of the conventional block for both 6 MV and 18 MV, respectively. The LAD-1/2 and LAD-TRN conformations were virtually identical, although it is proven analytically that the LAD-1/2 convention has the least overall area discrepancy of all conventions. CONCLUSIONS: The five MLC conformation conventions resulted in similar dosimetric penumbrae for all field shapes studied. The LAD-1/3, LAD-TRN, and LAD-1/2 produced the more favorable approximation to conventional block. The field penumbra width, although useful for evaluating irregular field shapes, could not describe the large local variations in the penumbra along the field edge for the MLC. These local variations could be of clinical concern when they appear near vital organs. However, the variation in a local region can potentially be reduced by minimizing the jaggedness of the leaf steps in that local region. The dosimetric results were useful as guidelines for the clinicians in the evaluation and adjustment of MLC leaf positions.

Head and Neck Neoplasms↗

Conformal prostate brachytherapy: initial experience of a phase I/II dose-escalating trial.

PURPOSE: To improve treatment results on prostatic adenocarcinoma, conformal radiation therapy (CRT) has been used. Two major drawbacks of external CRT are: (a) internal organ motion/daily set-up variations, and (b) exclusion of several patients for CRT based on poor geometrical relationships as identified by three dimensional (3D) treatment planning. To overcome the above problems, we began the first prospective Phase I/II dose-escalating clinical trial of conformal brachytherapy (CB) and concurrent external beam irradiation. METHODS AND MATERIALS: Fifty-nine patients with T2b-T3c prostatic adenocarcinoma received 176 transperineal ultrasound-guided conformal high-dose rate (HDR) boost implants. All patients received concomitant external beam pelvic irradiation. Dose escalation of the three HDR-CB fractions proceeded as follows: 5.5 Gy (30 patients), 6 Gy (20 patients), and 6.5 Gy (9 patients). The CB dose was prescribed to the prostate contour as outlined using an online biplanar transrectal ultrasound probe. The urethra, anterior rectal wall, and prostate boundaries were identified individually and outlined at 5 mm intervals from the base to the apex of the gland. The CB using real-time ultrasound guidance with interactive online isodose distributions was performed on an outpatient basis. As needles were placed into the prostate, corrections for prostate displacement were recorded and the isodose distributions were recalculated to represent the new relationship between the needles, prostate, and normal structures. No computerized tomography (CT) planning or implant preplanning was required. RESULTS: No patient was rejected based on poor geometrical relation of pelvic structures. In every implant performed, prostate displacement was noted. Craniocaudal motion of the gland ranged from 0.5-2.0 cm (mean = 1.0 cm), whereas lateral displacement was 0.1-0.4 cm. With the interactive online planning system, organ motion was immediately detected, accounted for, and corrected prior to each HDR treatment. The rectal dose has ranged from 45 to 87%, and the urethral dose from 97 to 112% of the prostate dose. It is significant to note that operator dependence has been completely removed because the interactive online planning system uniformly guides the physicians. CONCLUSIONS: With ultrasound guidance and the interactive online dosimetry system, organ motion (as compared to external beam) is insignificant because it can be corrected during the procedure without increasing target volume margins. Common pitfalls of brachytherapy, including operator dependence and difficulty with reproducibility, have been eliminated with the intraoperative online planning system.

Adenocarcinoma↗

The cumulative verification image analysis tool for offline evaluation of portal images.

PURPOSE: Daily portal images acquired using electronic portal imaging devices contain important information about the setup variation of the individual patient. The data can be used to evaluate the treatment and to derive correction for the individual patient. The large volume of images also require software tools for efficient analysis. This article describes the approach of cumulative verification image analysis (CVIA) specifically designed as an offline tool to extract quantitative information from daily portal images. METHODS AND MATERIALS: The user interface, image and graphics display, and algorithms of the CVIA tool have been implemented in ANSCI C using the X Window graphics standards. The tool consists of three major components: (a) definition of treatment geometry and anatomical information; (b) registration of portal images with a reference image to determine setup variation; and (c) quantitative analysis of all setup variation measurements. The CVIA tool is not automated. User interaction is required and preferred. Successful alignment of anatomies on portal images at present remains mostly dependent on clinical judgment. Predefined templates of block shapes and anatomies are used for image registration to enhance efficiency, taking advantage of the fact that much of the tool's operation is repeated in the analysis of daily portal images. RESULTS: The CVIA tool is portable and has been implemented on workstations with different operating systems. Analysis of 20 sequential daily portal images can be completed in less than 1 h. The temporal information is used to characterize setup variation in terms of its systematic, random and time-dependent components. The cumulative information is used to derive block overlap isofrequency distributions (BOIDs), which quantify the effective coverage of the prescribed treatment area throughout the course of treatment. Finally, a set of software utilities is available to facilitate feedback of the information for treatment plan recalculation and to test various decision strategies for treatment adjustment. CONCLUSIONS: The CVIA tool provides comprehensive analysis of daily images acquired with electronic portal imaging devices. Its offline approach allows characterization of the nature of setup variation for the individual patient that would have been difficult to deduce using only a few daily or weekly portal images. Distribution of the tool will help establish an important database of setup variation from many clinics. The information derived from CVIA can also serve as the foundation to integrate treatment verification, treatment planning, and treatment delivery.

Computer Peripherals↗

Effects of treatment setup variation on beam's eye view dosimetry for radiation therapy using the multileaf collimator vs. the cerrobend block.

PURPOSE: The purpose of this study is to quantify and compare retrospectively the effects of treatment setup variation on beam's eye view (BEV) dosimetry for radiation therapy using a multileaf collimator (MLC) vs. cerrobend block. METHODS AND MATERIALS: A study was performed on a group of 18 patients with cancer of the head and neck, lung, and pelvis who were treated with irregularly shaped fields. The BEV dosimetry of the fields shaped with cerrobend blocks and the MLC was measured with films at the depth of dose prescription in a solid water phantom. A "one-half-leaf" insertion convention was used to shape the MLC. In addition, an average of 15 sequential daily port films was taken per patient during the course of radiotherapy. The port films were aligned with the prescription film for each patient. Systematic error and random error of treatment setup for each patient were calculated. The effects of setup variation were incorporated by convolving the patient portal imaging data with the corresponding BEV film dosimetry. Two parameters were used to quantify the BEV dosimetry. First, the field penumbra width was calculated, which represented the average of the normal separations between 20 and 80% isodose lines along the prescription outline. Second, the ratio of areas covered by the 90 and 20% isodose lines, A90/20, was determined. The BEV dosimetry was then characterized with and without the effects of treatment setup variation. In addition, the difference in BEV dosimetry between the cerrobend block and the MLC was used to estimate the corresponding changes in tumor control probability (TCP). These changes were also compared to the changes in TCP for the treatment with or without the effects of random setup variation. RESULTS: With or without daily setup variation, the use of cerrobend block was more favorable than the MLC in terms of the field penumbra width and A90/20 for all treatment sites. In the absence of daily variation, the MLC field penumbra width was on average 1.3 mm larger than that of the cerrobend block, and 0.9 mm larger in the presence of daily setup variation. Similarly, the ratio A90/20 of the cerrobend block was on average 0.03 larger than that of MLC without daily setup variation, and 0.02 with daily setup variation. The difference in field penumbra width and A90/20 between the MLC and the cerrobend block was slightly reduced due to the effects of daily setup variation. For both the cerrobend block and the MLC, daily setup variation produced a significant increase in the field penumbra width, 2.3 mm for the cerrobend block and 1.9 mm for the MLC, and a decrease in the A90/20, 0.06 for the former and 0.05 for the latter. The change due to the daily setup variation was about a factor of 2 larger than the changes due to replacing the cerrobend block with the MLC. Using the TCP model, the change in TCP due to the daily setup variation was more than a factor of 3 larger than the change in TCP due to replacing the cerrobend block with the MLC. It was noted that the average changes in the penumbra, the A90/20 and the TCP calculated for the patient population did not adequately describe the changes for the individual patient. CONCLUSION: Our results do not show significant dosimetric differences between the MLC and the cerrobend block in conventional radiation treatment, whether or not daily setup variation was taken into consideration. The effects of daily setup variation alone produced a larger dosimetric change. The same results were obtained when the data were applied to calculate changes in TCP. For optimal radiation therapy, efforts should be concentrated on reducing daily setup variation. Our results also demonstrate the importance of frequent evaluation of MLC treatment using electronic portal imaging devices.

Equipment Design↗

Intraoperative optimization of needle placement and dwell times for conformal prostate brachytherapy.

PURPOSE: Traditionally, transperineal prostate brachytherapy has been heavily operator dependent. To overcome this limitation, a treatment planning method was developed for intraoperative planning, guidance, and evaluation. In this setting, reliability, speed, and ease of understanding are primary considerations. This planning method has been implemented for ultrasound guided implants of the prostate, but can be extended for use in other body sites. METHODS AND MATERIALS: The length and cross-section of the target (prostate) and location of urethra and rectum are determined intraoperatively from live ultrasound imaging. The planning program then automatically generates a "reference plan" containing needle locations, dwell times, and the resulting isodose distribution. As needles are placed, this information is corrected to account for any deviation of needle placement or movement of the prostate. Once all needles are in place, the normalization is adjusted to reconcile remaining hot-spots with coverage of the target volume. Optimization is performed in three separate stages. Each stage works to enhance only a subset of the implant parameters. (a) Pattern Optimization attempts to find the most appropriate placement for the needles or catheters. It is based on the transverse contour of the target volume. Needles are placed uniformly around the perimeter, and interior needle positions are determined from the cross-sectional area and shape. Critical structures such as the urethra are explicitly avoided. This step provides the overall framework for the implant, and is not generally repeated. (b) Relative Dwell Time Optimization selects relative dwell times that will give the best uniformity of dose. It works by setting the relative dwell time in each source position inversely proportional to the dose delivered to that point by the other source positions. It is used in the reference plan, and is repeated as each needle is inserted. This provides dosimetric feedback to the physician, who can judge the effect of deviations from the reference plan. (c) Relative Volume Optimization is an interactive method for fine tuning the normalization based upon volume analysis. The volume analysis is presented in tabular and graphical form, both being updated rapidly as the normalization is adjusted. The information is formatted to help the operator judge coverage and uniformity. Special functions are provided that allow the operator to "jump" to special normalization values based on several indices of uniformity or uniformity/coverage. RESULTS: This system overcomes some conventional brachytherapy limitations. Rather than depend on the operator's intuitive judgement of where the needles should be placed, a global plan is generated and validated with full dose calculations. Immediate feedback is provided concerning the adequacy of placement and avoidance of critical structures. This information is provided in terms of actual tissue doses to the target volume and critical structures using point doses, isodose distributions, and volume analysis. Since the new method was introduced in January 1994, 33 implants have been performed. The needle placement method has been reliable in the clinic, with different doctors producing similar results on subsequent fractions for the same patient. CONCLUSION: The method of decomposing the optimization problem into several simple steps is capable of rapidly, consistently, and reliably designing conformal treatment plans of high uniformity. Operator dependence has been significantly reduced. We are adapting the method for other anatomic sites.

Brachytherapy↗

A multileaf collimator field prescription preparation system for conventional radiotherapy.

PURPOSE: The purpose of this work is to develop a prescription preparation system for efficient field shaping using a multileaf collimator that can be used in community settings as well as research institutions. The efficiency advantage of the computer-controlled multileaf collimator, over cerrobend blocks, to shape radiation fields has been shown in conformal treatments, which typically require complete volumetric computerized tomographic data for three-dimensional radiation treatment planning--a utility not readily available to the general community. As a result, most patients today are treated with conventional radiation therapy. Therefore, we believe that it is very important to fully use the same efficiency advantage of multileaf collimator as a block replacement in conventional practice. METHODS AND MATERIAL: The multileaf collimator prescription preparation system developed by us acquires prescription images from different sources, including film scanner and radiation treatment planning systems. The multileaf collimator angle and leaf positions are set from the desired field contour defined on the prescription image, by minimizing the area discrepancies. Interactive graphical tools include manual adjustment of collimator angle and leaf positions, and definition of portions of the field edges that require maximal conformation. Data files of the final leaf positions are transferred to the multileaf collimator controller via a dedicated communication link. RESULTS: We have implemented the field prescription preparation system and a network model for integrating the multileaf collimator and other radiotherapy modalities for routine treatments. For routine plan evaluation, isodose contours measured with film in solid water phantom at prescription depth are overlaid on the prescription image. Preliminary study indicates that the efficiency advantage of the MLC over cerrobend blocks in conformal therapy also holds true for conventional treatments. CONCLUSION: Our model of computer-controlled prescription, evaluation, and treatment using multileaf collimators can be effectively implemented in both community settings and research institutions. The resultant increase in treatment efficiency and accuracy is now available for conventional radiotherapy.

Equipment Design↗

A new model for "accept or reject" strategies in off-line and on-line megavoltage treatment evaluation.

PURPOSE: With megavoltage on-line imaging, a temporal record of the treatment setup variation is made available during the course of radiotherapy. This work describes the theoretical framework where the imaging data is incorporated as feedback for deriving off-line and on-line "accept or reject" decisions to improve the quality of radiotherapy on an individual patient basis. METHODS AND MATERIALS: A dynamic model of treatment setup variation is developed to describe: (a) the variations of multifraction treatment position and (b) the variation of measurement. Based on this model, a confidence region of subsequent treatment position is estimated from measurements of previous treatment position. The confidence region is compared with an allowance region of the treatment position, representing the acceptable margin of setup variation. The difference of the two regions are then evaluated to derive off-line and on-line "accept or reject" treatment decisions. RESULTS: The model was simulated retrospectively using sequential daily images from different treatment sites. "Accept or reject" decisions were produced for on-line and off-line applications. The results also demonstrate the ability of the model to include the effects of setup variation that drifted during the course of treatment. CONCLUSION: The preliminary result demonstrates that "accept or reject" treatment decisions can be derived quantitatively from on-line imaging data. The model shows potential to guide the physician and therapist in implementing efficient and accurate treatment adjustments. Further work is required to test the model in the clinical setting.

Humans↗

Optimization of leaf positions when shaping a radiation field with a multileaf collimator.

Computer-controlled multileaf collimators are receiving increasing acceptance for clinical use in radiation therapy due to their efficiency in shaping radiation fields. Because of the physical leaf width of the multileaf collimator, a smooth field contour prescribed by a physician is approximated by a staircase-shaped field boundary. The point of intersection with the prescribed field contour determines the error of the approximation and may affect the outcome of the treatment. This article provides analytically optimized solutions for leaf positioning based on two different geometric object functions.

Humans↗

[Cloning and sequencing of ntrBC genes from Azospirillum brasilense].

A gene library of Azospirillum brasilense Yu62 was constructed in EMBL3. The library was screened with PCR amplified fragment as a special probe. Ten positive plaques (EA1-EA10) were selected. Detection results showed they contained two different types of clones, representing as EA4 and EA9 respectively. Southern hybridization of EA4 displayed that target gene was located in a 2.9kb EcoRI fragment. Sequence of this fragment had allowed the position and identification of ntrC gene, which encoding a protein of 53469, consisted of 480 amino acids. In the upstream of ntrC, a complete ntrB coding region was also found, which encoding a protein of 43487, consisted of 400 amino acids. Homologous analysis of the deduced amino acid sequences of ntrC and ntrB from different bacteria demonstrated that A. brasilense was closer to Rhizobia than to other free-living diazotrophs.

Azospirillum brasilense↗

[A study on the factors influencing bFGF to improve wound healing in severe burn].

The factors influencing basic fibroblast growth factor (bFGF) to improve wound healing in severe burn were studied. Rats were subjected to 15% III degrees burn. The results showed that high activity of bFGF was maintained after escharectomy in early period. In treated group 84.0% of rats wound healing was observed on the 40th day, while it was 9.0% in control group. Heparin could enhance activity of bFGF to stimulate formation of granulation tissue, regeneration of capillary, proliferation of fibroblast and DNA synthesis. Control of infection was beneficial to preserve activity of bFGF. The authors believe that the proper time to use bFGF is one week after injury.

Animals↗

Integrated software tools for the evaluation of radiotherapy treatment plans.

PURPOSE: This article announces the availability of a convenient and useful software environment for the evaluation of three-dimensional (3D) radiotherapy treatment plans. MATERIALS AND METHODS: Using standards such as American National Standards for Information Systems C and the X Window System allowed us to bring the computation and display of dose-volume histograms, dose statistics, tumor control probabilities, normal tissue complication probabilities, and a figure of merit together under one user interface. These plan evaluation tools are not stand alone, but must interact with a 3D radiation therapy planning system to obtain the required dose matrices and patient anatomical contours. Installation of the software involves a programmer who writes a software bridge between the radiation therapy planning system and the tools, thereby providing access to local data files. This design strategy confines portability issues to one area of the software. RESULTS: Access to the other tools is through the Graphical Plan Evaluation Tool (GPET). GPET coordinates the use of each of the tools and provides graphical facilities for display of their results. Importantly, GPET assures that the displayed results of each tool have been computed with the same input specifications for all treatment plans being compared. For added convenience, the user can rearrange the resultant data to be reviewed in various ways on the video screen. The software design also allows incorporation of customized algorithms and input data for computing tumor control probability and normal tissue complication probabilities, since those currently available are controversial. CONCLUSION: The Graphical Plan Evaluation Tool unifies the simultaneous computation for several analytical tools and graphical display of their results. Within the constraints of the X Window System environment, this assemblage of software tools provides a portable, flexible, and convenient method for the quantitative evaluation of several radiotherapy treatment plans.

Dose-Response Relationship, Radiation↗

A multileaf collimator field prescription preparation system for conventional radiotherapy.

PURPOSE: The purpose of this work is to develop a prescription preparation system for efficient field shaping using a multileaf collimator that can be used in community settings as well as research institutions. The efficiency advantage of the computer-controlled multileaf collimator, over cerrobend blocks, to shape radiation fields has been shown in conformal treatments, which typically require complete volumetric computerized tomographic data for three-dimensional radiation treatment planning--a utility not readily available to the general community. As a result, most patients today are treated with conventional radiation therapy. Therefore, we believe that it is very important to fully use the same efficiency advantage of multileaf collimator as a block replacement in conventional practice. METHODS AND MATERIAL: The multileaf collimator prescription preparation systems developed by us acquires prescription images from different sources, including film scanner, and radiation treatment planning systems. The multileaf collimator angle and leaf positions are set from the desired field contour defined on the prescription image, by minimizing the area discrepancies. Interactive graphical tools include manual adjustment of collimator angle and leaf positions, and definition of portions of the field edges that require maximal conformation. Data files of the final leaf positions are transferred to the multileaf collimator controller via a dedicated communication link. RESULTS: We have implemented the field prescription preparation system and a network model for integrating the multileaf collimator and other radiotherapy modalities for routine treatments. For routine plan evaluation, isodose contours measured with film in solid water phantom at prescription depth are overlaid on the prescription image. Preliminary study indicates that the efficiency advantage of the MLC over cerrobend blocks in conformal therapy also holds true for conventional treatments. CONCLUSION: Our model of computer-controlled prescription, evaluation, and treatment using multileaf collimators can be effectively implemented in both community settings and research institutions. The resultant increase in treatment efficiency and accuracy is now available for conventional radiotherapy.

Humans↗

Flow cytometric analysis of the effects of in vitro exposure to vomitoxin (deoxynivalenol) on apoptosis in murine T, B and IgA+ cells.

The immunotoxic effects of the trichothecene vomitoxin (VT or deoxynivalenol) and other trichothecenes may be mediated by direct interaction with lymphocytes. In this study, flow cytometric cell cycle analysis was used in conjunction with phenotypic staining by specific fluorescein isothiocyanate antibody conjugates to assess the in vitro effects of VT and another protein synthesis inhibitor, cycloheximide (CHX), on apoptosis in specific T- and B-cell subsets within thymus, spleen and Peyer's patch (PP) cultures. Both VT and CHX markedly inhibited T-cell apoptosis in dexamethasone (9 alpha-fluoro-16 alpha-methylprednisolone)-induced (DEX+) cells isolated from thymus, spleen and PP. Apoptosis-associated internucleosomal DNA fragmentation in whole thymus cell lysates as measured by gel electrophoresis was qualitatively consistent with flow cytometry among the various treatment groups. VT and CHX induced apoptosis in untreated (DEX-) T, B. and IgA+ cells from spleen and PP, whereas the effects of VT and CHX on DEX-induced apoptosis in B and IgA+ cells from these sources were negligible. These findings indicate that VT could either inhibit or enhance programmed cell death in a concentration-dependent manner and that this was dependent on lymphocyte subset, tissue source and glucocorticoid induction.

Animals↗