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Biomedical subjects

X R Zhu

Publications and source records attributed to X R Zhu.

12 recordsLinked to original sources

Total scatter factors and tissue maximum ratios for small radiosurgery fields: comparison of diode detectors, a parallel-plate ion chamber, and radiographic film.

Two p-type diode detectors, a parallel-plate ion chamber, and radiographic film were used to measure total scatter factors and tissue maximum ratios (TMRs) for a stereotactic radiosurgery system with circular fields ranging from 5 to 50 mm in diameter. One diode has a square detection diagonal of 2.3 mm and the other diode has a circular detection diameter of 1 mm. It is found that the two diodes measured essentially the same total scatter factors for all field sizes. Total scatter factors measured by film are within 3% of diode values. Our results also suggest that the parallel-plate ion chamber could underestimate total scatter factors for fields as large as 15 mm in diameter, although it is recommended for field diameters > or = 12.5 mm. The total scatter factors used in our clinic are combined from data measured with the ion chamber and the 2-mm-diam diode. The combined total scatter factors generally agree with published data. While film overestimates TMRs for the smallest fields at large depths because of energy dependence of the film, the measurements with the 1-mm-diam diode agree with published data measured with thermoluminescent dosimeters. It is demonstrated that the accurate measurements of total scatter factors and TMRs for small fields can be obtained by combining results of the commercially available detectors used in this study.

Biophysical Phenomena

Structural and functional characterization of Kv6.2 a new gamma-subunit of voltage-gated potassium channel.

We have cloned and functionally expressed Kv6.2, a new member of the Kv6 subfamily of voltage-gated potassium channel subunits. The human Kv6.2 (KCNF2) gene was mapped at 18q22-18q23. Kv6.2 mRNA is preferentially expressed in rat and human myocard. Rat and human Kv6.2 subunits appear to be unable to form functional Kv channels in a heterologous expression system, but, when coexpressed with Kv2.1 alpha subunits, heteromultimeric Kv channels were formed mediating voltage-activated delayed-rectifier type outward currents. Their kinetics and conductance-voltage relationship were different from those mediated by homomultimeric Kv2.1 channels. Yeast two-hybrid reporter assays indicated that Kv6.2 amino-termini are able to interact specifically with the Kv2.1 amino-terminus. It is proposed that this protein protein interaction underlies Kv2.1/Kv6.2 subunit assembly and the expression of functional heteromultimeric Kv2.1/Kv6.2 channels. The most resiliant feature of the Kv2.1/Kv6.2 channels was their submicromolar sensitivity to the antiarrhythmic drug propafenone. The data suggest that delayed-rectifier type channels containing Kv6.2 subunits may contribute to cardiac action potential repolarization.

Amino Acid Sequence

Characterization of human Kv4.2 mediating a rapidly-inactivating transient voltage-sensitive K+ current.

A human cDNA for the voltage-sensitive potassium channel subunit Kv4.2 has been cloned and functionally characterized. The human Kv4.2 (KCND2) gene was mapped at 7q31-32. Kv4.2 mRNA is prominently expressed in human brain. Relatively high concentrations of Kv4.2 mRNA occurred in mRNA preparations of amygdala, caudate nucleus, cerebellum, hippocampus, substantia nigra, and thalamus. Kv4.2 mRNA was not detected in human heart, kidney, liver, lung, pancreas, and skeletal muscle. The derived Kv4.2 open reading frame consists of 630 amino acids. In comparison to rat Kv4.2, the human Kv4.2 sequence is highly conserved showing amino acid sequence differences at five positions only. The Kv4.2 subunits were expressed heterologously in human embryonic kidney (293) cells and mediated a rapidly inactivating, A-type outward K+ current. The gating kinetics of the Kv4.2-mediated currents were very similar to those of rat Kv4.2-mediated currents. Both the Kv4.2 and Kv4.3 subunits have been implicated in mediating the transient outward K+ current Ito in rodent cardiac myocytes. In contrast we did not detect Kv4.2. but solely Kv4.3 mRNA in human heart RNA preparations. This may suggest that Kv4.2 subunits do not contribute to the rapid transient outward K+ current of atrial and ventricular myocytes in humans.

Amino Acid Sequence

Multiple machine implementation of enhanced dynamic wedge.

PURPOSE: After acquiring 4 years of experience with Dynamic Wedge, a software-driven one-dimensional (1D) compensation system, we implemented a new software version called Enhanced Dynamic Wedge (EDW). The EDW allows larger (30 cm) and asymmetric field sizes and additional angles for wedged fields. We implemented this software on four similar dual-energy accelerators that also possess upper and lower physical wedge sets. Our goal was to implement EDW with one common wedge factor (WF) table and one set of treatment-planning files. METHODS AND MATERIALS: We measured WFs with an ionization chamber and isodose profiles with both film and a diode array. We used a calculation scheme that requires only entry of the wedge angle and fixed jaw value. Filters for computerized treatment planning were configured for each wedge angle. We also examined to what degree the multileaf collimation (MLC) orientation, which is orthogonal to the EDW direction, was compromised for specific treatment sites. As a comparative test, we examined the dosimetric consistency for the 8 sets of physical wedges on the four machines. Finally, we updated our DW quality assurance program for EDW. RESULTS: The measured EDW WF was common for all four machines to within +/- 1.5% and the calculation scheme held to within 1.5%. The EDW isodoses were consistent among the machines as measured by film and diode array. The treatment-planning filters provided computed isodose profiles that were nearly identical to measured profiles. Regarding MLC orientation, we found that the collimator angle needed for EDW did not compromise isodose distributions, as apparent in measured isodoses and calculated dose-volume histograms. The consistency of the physical wedges did not fare as well. Two of the lower wedge sets had Wfs and profiles different (> 3%) from the other wedge sets. CONCLUSIONS: We have successfully implemented EDW on four machines using only one WF table and one set of treatment-planning filters. The EDW provides for improved treatment techniques for particular sites due to the large field sizes and additional angles available. Daily treatment efficiency has increased because of the remote capability provided by EDW.

Humans

Integrin-mediated short-term memory in Drosophila.

Volado is a new memory mutant of Drosophila. The locus encodes two isoforms of a new alpha-integrin, a molecule that dynamically mediates cell adhesion and signal transduction. The Volado gene is expressed preferentially in mushroom body cells, which are neurons known to mediate olfactory learning in insects. Volado proteins are concentrated in the mushroom body neuropil, brain areas that contain mushroom body processes in synaptic contact with other neurons. Volado mutants display impaired olfactory memories within 3 min of training, indicating that the integrin is required for short-term memory processes. Conditional expression of a Volado transgene during adulthood rescues the memory impairment. This rescue of memory is reversible, fading over time along with expression of the transgene. Thus the Volado integrin is essential for the physiological processes underlying memory. We propose a model in which integrins act as dynamic regulators of synapse structure or the signalling events underlying short-term memory formation.

Amino Acid Sequence

Geometric and dosimetric analysis of multileaf collimation conformity.

BACKGROUND AND PURPOSE: There is concern over the stepped edges of multileaf collimator (MLC) fields for target coverage compared with those of cerrobend. Despite recent reports dispelling this concern, users are still cautious when using MLCs for small fields. Leaf orientation can be a problem if one is required to orient the leaves along an axis not ideal for conformity (such as dynamic or universal wedge cases). In this study we examined the dependence of MLC field conformity on field size and elongation. MATERIALS AND METHODS: We examined circles of varying diameter and ellipses of varying eccentricity with leaves oriented along the major and minor axes of ellipses. The tests were both geometric, comparing areas of overblocking or underblocking (leaves inside and outside the field), and dosimetric, using radiographic films at depth in the beam's eye view plane. RESULTS: For the geometric comparison there is a rapid increase in non-conformity, defined as the percentage of overblocking or underblocking area, as the circle diameter decreases. For ellipses, when the leaves move along one axis direction, the conformity does not depend on the diameter of the same axis, but instead improves as the dimension of the axis in the non-leaf motion direction increases. The best conformity is achieved when the maximum number of leaves is used to shape the field. When the dosimetry is analyzed, the predictability of these trends decreases due to the impact of undulations (scatter), leaf inaccuracies and dosimetric uncertainties. CONCLUSIONS: We recommend that for small round fields MLC should be used with caution and that for ellipses the direction of leaf movement should be aligned with the minor axis whenever possible. Though these experiments are for idealized geometries, the observations can be applied to clinical fields. An MLC with a thinner leaf width could be beneficial for small round fields.

Humans

The influence of angular misalignment on fixed-portal intensity modulated radiation therapy.

A method has been developed to estimate potential dose errors due to linear accelerator angular setting misalignments of Intensity Modulated Radiation Therapy (IMRT) treatments. A first-order approximation to the dose error at a point is modeled as the dot product of the dose gradient and the shift vector of the point due to the rotational error. The analysis method is applied to a previously published set of optimized fluences for a 50 MV IMRT pelvis irradiation. Three of the published cases exhibiting a wide range of modulation are presented; a rectangular open field, a field optimized for a static multileaf collimator defining the portal outline coupled with a single broad bremsstrahlung profile modulation, and a fully modulated field using a physical modulator. To examine the energy dependence of angle setting errors, the study is repeated using the same fluence distributions, but with a dose-spread kernel appropriate for a 6 MV photon beam. The collimator angle error is set to 2 degree, and the dose error determined with both a centrally located isocenter and an isocenter chosen to model a split-field geometry. The dose error due to a 2 degree gantry setting error is assessed at a plane 10 cm distal to the isocenter. The mathematical form of the dose error due to couch motion is similar to the other two errors, so the dose error resulting from a couch angle missetting is not presented. The magnitude of the errors is largest for the 6 MV beam, while the volume encompassed by the errors is greater for the 50 MV beam. The gantry error yields the largest dose error values, with the 6 MV modulated case presenting dose errors of greater than 40%.

Humans

minibrain: a new protein kinase family involved in postembryonic neurogenesis in Drosophila.

The development of the adult central nervous system of Drosophila requires a precise and reproducible pattern of neuroblast proliferation during postembryonic neurogenesis. We show here that mutations in the minibrain (mnb) gene cause an abnormal spacing of neuroblasts in the outer proliferation center (opc) of larval brain, with the implication that mnb opc neuroblasts produce less neuronal progeny than do wild type. As a consequence, the adult mnb brain exhibits a specific and marked size reduction of the optic lobes and central brain hemispheres. The insufficient number of distinct neurons in mnb brains is correlated with specific abnormalities in visual and olfactory behavior. The mnb gene encodes a novel, cell type-specific serine-threonine protein kinase family that is expressed and required in distinct neuroblast proliferation centers during postembryonic neurogenesis. The mnb kinases share extensive sequence similarities with kinases involved in the regulation of cell division.

Amino Acid Sequence

A convolution-adapted ratio-TAR algorithm for 3D photon beam treatment planning.

A convolution-adapted ratio of tissue-air ratios (CARTAR) method of dose calculation has been developed at the Mallinckrodt Institute of Radiology. This photon pencil-beam algorithm has been developed and implemented specifically for three-dimensional treatment planning. In a standard ratio of tissue-air ratios (RTAR) algorithm, doses to points in irregular field geometries are not adequately modeled. This is inconsistent with the advent of conformal therapy, the goal of which is to conform the dose distribution to the target volume while sparing neighboring sensitive normal critical structures. This motivated us to develop an algorithm that can model the beam penumbra near irregular field edges, while retaining much of the speed for the original RTAR algorithm. The dose calculation algorithm uses two-dimensional (2D) convolutions, computed by 2D fast Fourier transform, of pencil-beam kernels with a beam transmission array to calculate 2D off-axis profiles at a series of depths. These profiles are used to replace the product of the transmission function and measured square-field boundary factors used in the standard RTAR calculation. The 2D pencil-beam kernels were derived from measured data for each modality using commonly available dosimetry equipment. The CARTAR algorithm is capable of modeling the penumbra near block edges as well as the loss of primary and scattered beam in partially blocked regions. This paper describes the dose calculation algorithm, implementation, and verification.

Algorithms

Measurement of a photon penumbra-generating kernel for a convolution-adapted ratio-TAR algorithm for 3D treatment planning.

A method has been developed to measure a photon penumbra-generating kernel using dosimetry equipment available in most radiation therapy departments. The kernel is used in a convolution-adapted ratio-TAR algorithm in our three-dimensional treatment planning system. The kernel is assumed to be invariant with respect to off-axis position, axially symmetric, and is divided into short- and long-range components, with a different measurement technique for each. The data required to obtain the short-range component are measured by scanning across a split-field geometry incident on a water phantom. The derivative of the measured profile is proportional to one-dimensional projections across the kernel. Because the kernel is axially symmetric, only one profile measurement is required for each depth. A CT reconstruction technique is used to extract the radial dependence of the kernel from the strip integrals. Electronic noise in the acquisition system yields significant uncertainties in the kernel shape for distances beyond 3 cm. The long-range portion of the kernel is obtained by examining tissue-air ratios (TARs). The derivative of the TAR at the center of a circular field is proportional to the kernel value at the distance corresponding to the radius of the field. The kernel measurement method was tested by comparing measured and calculated square-field profiles at a variety of depths. Agreement was within 1% within the field boundary and 3% outside the field boundary for all depths.

Algorithms

Frequenin--a novel calcium-binding protein that modulates synaptic efficacy in the Drosophila nervous system.

The T(X;Y)V7 rearrangement in Drosophila has originally been recognized as a Shaker-like mutant because of its behavioral and electrophysiological phenotype. The gene whose expression is altered by the V7 rearrangement has been characterized. It encodes a novel Ca(2+)-binding protein named frequenin, which is related to recoverin and visinin. In vitro, the frequenin protein functions like recoverin as a Ca(2+)-sensitive guanylyl cyclase activator. Anti-frequenin antibodies stain the central and peripheral nervous system in Drosophila embryos and in larval and adult tissue sections. Frequenin appears to be particularly enriched in synapses, such as the motor nerve endings at neuromuscular junctions. Neuromuscular junctions of transgenic flies, which overexpress frequenin upon heat shock, exhibit an extraordinarily enhanced, frequency-dependent facilitation of neurotransmitter release, with properties identical to those observed in V7 junctions. We propose that frequenin represents a new element for the Ca(2+)-dependent modulation of synaptic efficacy.

Amino Acid Sequence

Cloning of the crystalline cell wall protein gene of Bacillus licheniformis NM 105.

A protein with a tetragonal pattern, defined as RS protein, was found on the wall surface of an alkaline phosphatase secretion-deficient mutant (NM 105) of Bacillus licheniformis 749/C. The protein was present on the wall surface of the exponential-growth-phase cells, but at the stationary growth phase it was overproduced and hypersecreted. This protein was precipitated to homogeneity from the culture fluid by 80% ammonium sulfate saturation and chilled acetone. The molecular mass of the protein was 98 kilodaltons, and it had a single subunit in a sodium dodecyl sulfate gel. Specific anti-RS antibody was generated in rabbits and used to immunolabel the RS protein on the cells at different growth phases. In early-exponential-growth-phase cells, the outside surface of the wall, the cytoplasm, and the inside surface of the cytoplasmic membrane were labeled. In stationary-growth-phase cells, the cytoplasm was poorly labeled, but the labeling on the outside surface of the wall was high. AB. licheniformis NM 105 gene library was made by using the lambda phage EMBL3. The RS protein expression from this gene library was detected by a modified autoradiographic procedure. One of the amplified RS protein-positive plaques (4213-1) containing recombinant DNA was chosen, and the restriction map of this DNA was prepared. The RS protein expressed in Escherichia coli NM 539 infected with 4213-1 recombinant phage had a lower molecular mass than the purified authentic RS protein. The 4.5-kilobase-pair (kbp) SalI-EcoRI fragment of the recombinant DNA was cloned in the shuttle plasmid pMK4 to construct pMK462, which was expressed in B. subtilis MI112 and produced the RS protein identical in molecular mass to the purified authentic RS protein. The RS protein expression was also demonstrated in cryosections of transformed E. coli and B. subtilis cells by immunoelectron microscopy. The 1.2-kbp SalI-HindIII and 1.8-kbp HindIII-HindIII recombinant DNA restriction enzyme fragments, respectively, from the right of the restriction map produced anti-RS antibody cross-reacting proteins. The expression of the 1.2-kbp SalI-HindIII DNA fragment cloned in pUC8 could be induced with isopropyl-beta-D-thiogalactopyranoside. The 1.8-kbp DNA restriction fragment hybridized with both the chromosomal DNA of strain NM 105 and the recombinant phage 4213-1 DNA. The RS gene expression was finally demonstrated in transformed E. coli 539 cells by in situ hybridization of frozen thin sections with the 1.8-kbp HindIII biotin-dATP probe and immunolabeling these with anti-biotin immunoglobulin G and protein A-gold.

Bacillus