Biomedical subjects

L Xing

Publications and source records attributed to L Xing.

At least 37 records · Page 2Linked to original sources

PubMed2000

Phytoreovirus T = 1 core plays critical roles in organizing the outer capsid of T = 13 quasi-equivalence.

The structures of the double-shelled rice dwarf virus and of its single-shell core have been determined by cryoelectron microscopy and image reconstruction. The core carries a prominent density located at each of the icosahedral faces of its T = 1 lattice. These protrusions are formed by outer shell trimers, tightly inserted at the threefold positions of the core. Such configuration of the core may guide the assembly of the outer shell, aided by lateral interactions between its subunits, into a T = 13 lattice. The organization of the phytoreovirus capsid elucidates for the first time a general model for assembling two unique T numbers of quasi-equivalence.

Animals↗

PubMed2000

Distinct cellular receptor interactions in poliovirus and rhinoviruses.

Receptor binding to human poliovirus type 1 (PV1/M) and the major group of human rhinoviruses (HRV) was studied comparatively to uncover the evolution of receptor recognition in picornaviruses. Surface plas- mon resonance showed receptor binding to PV1/M with faster association and dissociation rates than to HRV3 and HRV16, two serotypes that have similar binding kinetics. The faster rate for receptor association to PV1/M suggested a relatively more accessible binding site. Thermodynamics for receptor binding to the viruses and assays for receptor-mediated virus uncoating showed a more disruptive receptor interaction with PV1/M than with HRV3 or HRV16. Cryo-electron microscopy and image reconstruction of receptor-PV1/M complexes revealed receptor binding to the 'wall' of surface protrusions surrounding the 'canyon', a depressive surface in the capsid where the rhinovirus receptor binds. These data reveal more exposed receptor-binding sites in poliovirus than rhinoviruses, which are less protected from immune surveillance but more suited for receptor-mediated virus uncoating and entry at the cell surface.

Animals↗

PubMed2000

Gene discovery using the maize genome database ZmDB.

Zea mays DataBase (ZmDB) is a repository and analysis tool for sequence, expression and phenotype data of the major crop plant maize. The data accessible in ZmDB are mostly generated in a large collaborative project of maize gene discovery, sequencing and phenotypic analysis using a transposon tagging strategy and expressed sequence tag (EST) sequencing. ESTs constitute most of the current content. Database search tools, convenient links to external databases, and novel sequence analysis programs for spliced alignment are provided and together serve as an efficient protocol for gene discovery by sequence inspection. ZmDB can be accessed at http://zmdb. iastate.edu. ZmDB also provides web-based ordering of materials generated in the project, including EST and genomic DNA clones, seeds of mutant plants and microarrays of amplified EST and genomic DNA sequences.

Amino Acid Sequence↗

PubMed2000

Breast-conserving radiation therapy using combined electron and intensity-modulated radiotherapy technique.

BACKGROUND AND PURPOSE: To explore the feasibility of a multi-modality breast-conserving radiation therapy treatment technique to reduce high dose to the ipsilateral lung and the heart when compared with the conventional treatment technique using two tangential fields. MATERIALS AND METHODS: An electron beam with appropriate energy was combined with four intensity modulated photon beams. The direction of the electron beam was chosen to be tilted 10-20 degrees laterally from the anteroposterior direction. Two of the intensity-modulated photon beams had the same gantry angles as the conventional tangential fields, whereas the other two beams were rotated 15-25 degrees toward the anteroposterior directions from the first two photon beams. An iterative algorithm was developed which optimizes the weight of the electron beam as well as the fluence profiles of the photon beams for a given patient. Two breast cancer patients with early-stage breast tumors were planned with the new technique and the results were compared with those from 3D planning using tangential fields as well as 9-field intensity-modulated radiotherapy (IMRT) techniques. RESULTS: The combined electron and IMRT plans showed better dose conformity to the target with significantly reduced dose to the ipsilateral lung and, in the case of the left-breast patient, reduced dose to the heart, than the tangential field plans. In both the right-sided and left-sided breast plans, the dose to other normal structures was similar to that from conventional plans and was much smaller than that from the 9-field IMRT plans. The optimized electron beam provided between 70 to 80% of the prescribed dose at the depth of maximum dose of the electron beam. CONCLUSIONS: The combined electron and IMRT technique showed improvement over the conventional treatment technique using tangential fields with reduced dose to the ipsilateral lung and the heart. The customized beam directions of the four IMRT fields also kept the dose to other critical structures to a minimum.

Breast Neoplasms↗

PubMed2000

Dosimetric effects of patient displacement and collimator and gantry angle misalignment on intensity modulated radiation therapy.

PURPOSE AND OBJECTIVE: The primary goal of this study was to examine systematically the dosimetric effect of small patient movements and linear accelerator angular setting misalignments in the delivery of intensity modulated radiation therapy. We will also provide a method for estimating dosimetric errors for an arbitrary combination of these uncertainties. MATERIALS AND METHODS: Sites in two patients (lumbar-vertebra and nasopharynx) were studied. Optimized intensity modulated radiation therapy treatment plans were computed for each patient using a commercially available inverse planning system (CORVUS, NOMOS Corporation, Sewickley, PA). The plans used nine coplanar beams. For each patient the dose distributions and relevant dosimetric quantities were calculated, including the maximum, minimum, and average doses in targets and sensitive structures. The corresponding dose volumetric information was recalculated by purposely varying the collimator angle or gantry angle of an incident beam while keeping other beams unchanged. Similar calculations were carried out by varying the couch indices in either horizontal or vertical directions. The intensity maps of all the beams were kept the same as those in the optimized plan. The change of a dosimetric quantity, Q, for a combination of collimator and gantry angle misalignments and patient displacements was estimated using Delta=Sigma(DeltaQ/Deltax(i))Deltax(i). Here DeltaQ is the variation of Q due to Deltax(i), which is the change of the i-th variable (collimator angle, gantry angle, or couch indices), and DeltaQ/Deltax(i) is a quantity equivalent to the partial derivative of the dosimetric quantity Q with respect to x(i). RESULTS: While the change in dosimetric quantities was case dependent, it was found that the results were much more sensitive to small changes in the couch indices than to changes in the accelerator angular setting. For instance, in the first example in the paper, a 3-mm movement of the couch in the anterior-posterior direction can cause a 38% decrease in the minimum target dose or a 41% increase in the maximum cord dose, whereas a 5 degrees change in the θ(1)=20 degrees beam only gave rise to a 1.5% decrease in the target minimum or 5.1% in the cord maximum. The effect of systematic positioning uncertainties of the machine settings was more serious than random uncertainties, which tended to smear out the errors in dose distributions. CONCLUSIONS: The dose distribution of an intensity modulated radiation therapy (IMRT) plan changes with patient displacement and angular misalignment in a complex way. A method was proposed to estimate dosimetric errors for an arbitrary combination of uncertainties in these quantities. While it is important to eliminate the angular misalignment, it was found that the couch indices (or patient positioning) played a much more important role. Accurate patient set-up and patient immobilization is crucial in order to take advantage fully of the technological advances of IMRT. In practice, a sensitivity check should be useful to foresee potential IMRT treatment complications and a warning should be given if the sensitivity exceeds an empirical value. Quality assurance action levels for a given plan can be established out of the sensitivity calculation.

Humans↗

PubMed2000

Monitor unit calculation for an intensity modulated photon field by a simple scatter-summation algorithm.

An important issue in intensity modulated radiation therapy (IMRT) is the verification of the monitor unit (MU) calculation of the planning system using an independent procedure. Because of the intensity modulation and the dynamic nature of the delivery process, the problem becomes much more involved than that in conventional radiation therapy. In this work, a closed formula for MU calculation is derived. The approach is independent of the specific form of leaf sequence algorithms. It is straightforward to implement the procedure using a simple computer program. The approach is illustrated by a simplified example and is demonstrated by a few CORVUS (NOMOS Corporation, Sewickley, PA) treatment plans. The results indicate that it is robust and suitable for IMRT MU verification.

Algorithms↗

PubMed2000

Monte Carlo verification of IMRT dose distributions from a commercial treatment planning optimization system.

The purpose of this work was to use Monte Carlo simulations to verify the accuracy of the dose distributions from a commercial treatment planning optimization system (Corvus, Nomos Corp., Sewickley, PA) for intensity-modulated radiotherapy (IMRT). A Monte Carlo treatment planning system has been implemented clinically to improve and verify the accuracy of radiotherapy dose calculations. Further modifications to the system were made to compute the dose in a patient for multiple fixed-gantry IMRT fields. The dose distributions in the experimental phantoms and in the patients were calculated and used to verify the optimized treatment plans generated by the Corvus system. The Monte Carlo calculated IMRT dose distributions agreed with the measurements to within 2% of the maximum dose for all the beam energies and field sizes for both the homogeneous and heterogeneous phantoms. The dose distributions predicted by the Corvus system, which employs a finite-size pencil beam (FSPB) algorithm, agreed with the Monte Carlo simulations and measurements to within 4% in a cylindrical water phantom with various hypothetical target shapes. Discrepancies of more than 5% (relative to the prescribed target dose) in the target region and over 20% in the critical structures were found in some IMRT patient calculations. The FSPB algorithm as implemented in the Corvus system is adequate for homogeneous phantoms (such as prostate) but may result in significant under or over-estimation of the dose in some cases involving heterogeneities such as the air-tissue, lung-tissue and tissue-bone interfaces.

Computer Simulation↗

PubMed2000

Computer verification of fluence map for intensity modulated radiation therapy.

In a treatment planning system for intensity modulated radiation therapy (IMRT), the time sequence of multileaf collimator (MLC) settings are derived from an optimal fluence map as a postoptimization process using a software module called a "leaf sequencer." The dosimetric accuracy of the dynamic delivery depends on the functionality of the module and it is important to verify independently the correctness of the leaf sequences for each field of a patient treatment. This verification is unique to the IMRT treatment and has been done using radiographic film, electronic portal imaging device (EPID) or electronic imaging system (BIS). The measurement tests both the leaf sequencer and the dynamic multileaf collimator (MLC) delivery system, providing a reliable assurance of clinical IMRT treatment. However, this process is labor intensive and time consuming. In this paper, we propose to separate quality assurance (QA) of the leaf sequencer from the dynamic MLC delivery system. We describe a simple computer algorithm for the verification of the leaf sequences. The software reads in the leaf sequences and simulates the motion of the MLC leaves. The generated fluence map is then compared quantitatively with the reference map from the treatment planning system. A set of pre-defined QA indices is introduced to measure the "closeness" between the computed and the reference maps. The approach has been used to validate the CORVUS (NOMOS Co., Sewickley, PA) treatment plans. The results indicate that the proposed approach is robust and suitable to support the complex IMRT QA process.

Algorithms↗

PubMed2000

A dose-volume histogram based optimization algorithm for ultrasound guided prostate implants.

The task of treatment planning for prostate implants is to find an optimal seed configuration, comprising the target coverage and dosimetric consideration of critical structures such as the rectum and urethra. An efficient method to accomplish this is to use an inverse planning technique that derives the optimized solution from a prescribed treatment goal. The goal can be specified in the voxel domain as the desired doses to the voxels of the target and critical structures, or in the dose volume representation as the desired dose volume histograms (DVHs) of the target and critical structures. The DVH based optimization has been successfully used in plan optimization for intensity-modulated radiation therapy (IMRT) but little attention has been paid to its application in prostate implants. Clinically, it has long been known that some normal structure tolerances are more accurately assessed by volumetric information. Dose-volume histograms are also widely used for plan evaluation. When working in the DVH domain for optimization one has more control over the final DVHs. We have constructed an objective function sensitive to the DVHs of the target and critical structures. The objective function is minimized using an iterative algorithm, starting from a randomly selected initial seed configuration. At each iteration step, a trial position is given to a randomly selected source and the trial position is accepted if the objective function is decreased. To avoid being trapped in a less optimal local minimum, the optimization process is repeated. The final plan is selected from a pool of optimized plans obtained from a series of randomized initial seed configurations.

Algorithms↗

PubMed2000

Beam orientation optimization in intensity-modulated radiation treatment planning.

Beam direction optimization is an important problem in radiation therapy. In intensity modulated radiation therapy (IMRT), the difficulty for computer optimization of the beam directions arises from the fact that they are coupled with the intensity profiles of the incident beams. In order to obtain the optimal incident beam directions using iterative or stochastic methods, the beam profiles ought to be optimized after every change of beam configuration. In this paper we report an effective algorithm to optimize gantry angles for IMRT. In our calculation the gantry angles and the beam profiles (beamlet weights) were treated as two separate groups of variables. The gantry angles were sampled according to a simulated annealing algorithm. For each sampled beam configuration, beam profile calculation was done using a fast filtered backprojection (FBP) method. Simulated annealing was also used for beam profile optimization to examine the performance of the FBP for beam orientation optimization. Relative importance factors were incorporated into the objective function to control the relative importance of the target and the sensitive structures. Minimization of the objective function resulted in the best possible beam orientations and beam profiles judged by the given objective function. The algorithm was applied to several model problems and the results showed that the approach has potential for IMRT applications.

Algorithms↗

PubMed2000

Inverse planning incorporating organ motion.

Accurate targeting is important in intensity-modulated radiation therapy (IMRT). The positional uncertainties of structures with respect to the external beams arise in part from random organ motion and patient setup errors. While it is important to improve immobilization and reduce the influence of organ motion, the residual effects should be included in the IMRT plan design. Current inverse planning algorithms follow the conventional approach and include uncertainties by assuming population-based margins to the target and sensitive structures. Margin around a structure represents a "hard boundary" and the fact that a structure has a spatial probability distribution has been completely ignored. With increasing understanding of spatial uncertainties of structures and the technical capability of fine-tuning the dose distribution on an individual beamlet level in IMRT, it seems timely and important to fully utilize the information in the planning process. This will reduce the "effective" margins of the structures and facilitate dose escalation. Instead of specifying a "hard margin," we describe an inverse planning algorithm which takes into consideration positional uncertainty in terms of spatial probability distribution. The algorithm was demonstrated by assuming that the random organ motion can be represented by a three-dimensional Gaussian distribution function. Other probability distributions can be dealt with similarly. In particular, the commonly used "hard margin" is a special case of the current approach with a uniform probability distribution within a specified range. The algorithm was applied to plan treatment for a prostate case and a pancreatic case. The results were compared with those obtained by adding a margin to the clinical target volume. Better sparing of the sensitive structures were obtained in both cases using the proposed method for approximately the same target coverage.

Algorithms↗

PubMed2000

c-Src signaling induced by the adapters Sin and Cas is mediated by Rap1 GTPase.

Oncogenic Src proteins have been extensively studied to gain insight into the signaling mechanisms of Src. To better understand signaling through wild-type Src, we used an approach that involves activation of Src signaling through the binding of physiologic ligands to the Src SH3 domain. To this end, we used full-length and truncated versions of the multiadapter molecules Cas and Sin to activate c-Src, and we examined the intracellular pathways that mediate Src signaling under these conditions. We show that although all proteins bind to and are phosphorylated by c-Src, quantitative differences exist in the ability of the different ligands to activate c-Src signaling. In addition, we show that Sin- and Cas-induced Src signaling, as assayed by transcriptional activation, is exclusively mediated through a pathway that involves the adapter Crk and the GTP-binding protein Rap1. These data are in contrast to previous observations showing Ras to mediate signaling downstream of transforming Src alleles. In our system, we found that signaling through the oncogenic SrcY527 mutant is indeed mediated by Ras. In addition, we found that Rap1 also mediates oncogenic Src signaling. Our results show for the first time that Rap1 mediates c-Src kinase signaling and reveal mechanistic differences in the signaling properties of wild-type and transforming Src proteins.

Adaptor Proteins, Signal Transducing↗

PubMed2000

Adenovirus-mediated expression of antisense RNA transcripts complementary to pig alpha(1,3) galactosyltransferase mRNA inhibits expression of Gal alpha(1,3) Gal epitope.

AIM: To examine the effects of the expression of antisense RNA transcripts complementary to the pig alpha(1,3) galactosyltransferase [alpha(1,3)GT]mRNA on the expression of Gal alpha(1,3) Gal structure (gal epitope) in cultured cell lines. METHODS: Human adenoviral vectors were used to mediate the expression of antisense RNA. The expression levels of H blood group antigens and gal epitopes were analyzed by flow cytometry using FITC-UEA-I and FITC-GS-IB4 lectins, respectively. RESULTS: Recombinant adenoviruses, Ad5anti-sGT600 and Ad5-anti-sGT1100, which express antisense RNA complementary to different regions of the pig alpha(1,3) GT mRNA, were constructed and used to infect cell line of NIH3T3. The results showed about 30% reduction in the expression level of gal epitopes on the surface of NIH3T3 cells. In addition, co-expression of human secretor type alpha(1,2) fucosyltransferase [alpha(1,2)FT]cDNA and antisense RNA complementary to the pig alpha(1,3) GT mRNA led to a further reduction in the gal epitope level. CONCLUSION: Recombinant adenoviruses, Ad5anti-sGT600 and Ad5anti-sGT1100, are effective to down-regulate the gal epitope expression.

3T3 Cells↗

PubMed2000

FUT2 gene involved in expression of H blood group antigen on surface of human tumor cell lines BEL-7404, SGC-7901, and SPC-A-1.

AIM: To investigate the expression of blood group H antigen on the surface of several human tumor cell lines such as BEL-7404, SPC-A-1, and SGC-7901. METHODS: In vitro and in vivo expression of the blood group H antigen was analyzed with flow cytometry and immunohistochemistry. Expression of FUT2 gene was determined by RT-PCR, Southern blot, and restriction digestion. RESULTS: Flow cytometric analysis showed that SGC-7901 cells, BEL-7404 cells, and SPC-A-1 cells had mean fluorescence intensity (MFI) values of 162 +/- 43, 81 +/- 25, and 28 +/- 17, respectively. DNA fragments of about 1.0 kb in length were obtained by RT-PCR from RNA isolated from these cells and were detected by FUT2-specific [alpha-32P]dATP labeled DNA probes. CONCLUSION: Human tumor cell lines BEL-7404, SGC-7901, and SPC-A-1 all expressed blood group H antigen on their cell membranes in vitro and in vivo, but their expression levels varied significantly between different cell lines. FUT2 gene expression resulted in the production of these antigens on the cell membrane.

3T3 Cells↗

PubMed2000

Adenovirus-mediated expression of human secretor type alpha(1,2) fucosyltransferase reduces level of Gal alpha(1,3)Gal epitope.

AIM: To test the potential of human secretor type alpha(1, 2) fucosyltransferase [Se alpha(1,2)FT] to downregulate the expression of Gal alpha(1,3)Gal epitope (gal epitope) in cultured cell lines. METHODS: Expression of Se alpha(1,2) FT was mediated by human adenoviral vector. Flow cytometric analysis was used to compare the expression level of H blood group antigen or gal epitope. MTT was employed to assess the susceptibility of mouse NIH3T3 cells to human natural antibody and complement mediated lysis. RESULTS: A recombinant replication-deficient adenovirus (rAdv) containing human Se alpha(1,2)FT cDNA (Ad5hSeFT) was designed and successfully constructed. Flow cytometric analysis showed that after mock infection, Ad5null infection, and Ad5hSeFT infection, the mean fluorescence intensity (MFI) values for the binding of Ulex europaeus I (UEA-I) lectin to NIH3T3 cells were 2.3 +/- 0.6, 2.1 +/- 1.0, and 36.5 +/- 5.9, respectively; MFI values for the binding of Griffonia simplicifolia isolectin B4 (GS-IB4) lectin to NIH3T3 cells were 167 +/- 23, 170 +/- 19, and 100 +/- 14, respectively; MFI values for the binding of human natural IgG and IgM antibodies to NIH3T3 cells were 31 +/- 3, 32 +/- 4, and 22 +/- 4, respectively. CONCLUSION: H blood group antigen was detected on NIH3T3 cells after Ad5hSeFT infection and resulted in more than 40% reduction in the level of gal epitope on the cell surface. This reduction increased the resistance of NIH3T3 cells to lysis by normal human serum.

3T3 Cells↗

PubMed2000

[Detection of core promoter mutations in chronic hepatitis B].

OBJECTIVE: To study the core promoter mutation in chronic hepatitis B and its effect on viral serology. METHODS: HBV core promoter gene fragments were amplified by using mismatched PCR combined with a restriction fragment length polymorphism assay. The PCR products were digested with Bcl I and subjected to electrophoresis on agarose gels. RESULTS: We investigated the core promoter mutation in 89 patients with HBV DNA positive. The patterns of restriction fragment length polymorphism (RFIP) of the core promoter gene were distinguished and verified by direct sequencing. The combined mutations of nucleotides (nt) 1762 and 1764 in the core promoter from A to T and G to A were detected in 47 individuals, 21 of 43 HBeAg positive patients and 26 of 46 anti- HBe positive cases were found infected with this combined mutant. These two groups showed no significant difference (P > 0.05). The combined mutation was found in 11 of the 15 patients with medium and severe chronic hepatitis. In 5 chronic hepatitis B patients with coexistence of wild-type and mutant a tendency of superior accumulation of mutant was found. CONCLUSIONS: This study suggests that the core promoter mutations commonly exist in Chinese chronic hepatitis B patients. The mutation can only reduce the pre-core mRNA transcribing efficiency, but cannot discontinue the synthesis of HBeAg. The effect on serology in this mutation is different from that in pre-core stop 28 mutation. The superior accumulation of mutations seems relating to the degree of chronic liver disease.

Adolescent↗

PubMed1999

Recombinant hepatitis E capsid protein self-assembles into a dual-domain T = 1 particle presenting native virus epitopes.

The three-dimensional structure of a self-assembled, recombinant hepatitis E virus particle has been solved to 22-A resolution by cryo-electron microscopy and three-dimensional image reconstruction. The single subunit of 50 kDa is derived from a truncated version of the open reading frame-2 gene of the virus expressed in a baculovirus system. This is the first structure of a T = 1 particle with protruding dimers at the icosahedral two-fold axes solved by cryo-electron microscopy. The protein shell of these hollow particles extends from a radius of 50 A outward to a radius of 135 A. In the reconstruction, the capsid is dominated by dimers that define the 30 morphological units. The outer domain of the homodimer forms a protrusion, which corresponds to the spike-like density seen in the cryo-electron micrograph. This particle retains native virus epitopes, suggesting its potential value as a vaccine.

Capsid↗

PubMed1999

Synchronizing dynamic multileaf collimators for producing two-dimensional intensity-modulated fields with minimum beam delivery time.

PURPOSE: Leaf motion synchronization of dynamic multileaf collimators (DMLC) for intensity-modulated radiotherapy (IMRT) is important in improving dose distribution and reducing "tongue-and-groove" effects for a prescribed intensity profile. Leaf synchronization could also be used in transforming a one-dimensional leaf-setting algorithm into a two-dimensional leaf-setting algorithm. In this work, we aim to develop a generalized leaf synchronization method for delivering IMRT with the minimized beam delivery time and the optimized subfield variations for a leaf-setting sequence. METHODS AND MATERIALS: With the leaf synchronization procedure, all active MLC leaf pairs start and finish off a leaf sequence simultaneously. In this work, the MLC leaf pairs were synchronized under the condition that the resulting leaf sequence produces the desired intensity profile with the minimum beam delivery time. The parameter of the leaf synchronization function was determined through the least-square minimization of the area variations of all subfields within a leaf sequence. The leaf synchronization and optimization procedure were applied and analyzed for clinical relevant intensity profiles for treating the head-and-neck cancer patients using IMRT. RESULTS: The total monitor units and the optimized beam delivery time of generating a two-dimensional intensity profile was proven through this work to be the global minimum of all leaf-setting sequences including the unsynchronized leaf-setting sequences. The optimized parameter for subfield variations of the synchronized leaf trajectories was found to be dependent on individual intensity profiles. For all our studied cases, the unsynchronized leaf trajectories always have significantly larger subfield variations than the synchronized leaf trajectories. CONCLUSION: It is important and also feasible to synchronize and optimize dynamic MLC leaf motions while still keeping the total beam delivery time minimum for delivering arbitrary two-dimensional intensity-modulated fields.

Algorithms↗