bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensive perspective on the mechanism of preferred orientation in reactive-sputter-deposited nitrides
Authors: Kajikawa Yuya , Noda Suguru , Komiyama Hiroshi
Published: November 2003

Texture control of sputter-deposited nitride films has provoked a great deal of interest due to its technological importance. Despite extensive research, however, the reported results are scattered and discussions about the origin of preferred orientation (PO) are sometimes conflicting, and therefore controversial. The aim of this study is to acquire a clear perspective in order to discuss the origin of PO of sputter-deposited nitrides. Among nitrides, we focus on titanium nitride (TiN), aluminum nitride (AlN), and tantalum nitride (TaN), which are three commonly used nitrides. First, we collected reported experimental results about the relation between operating conditions and PO, because PO is considered to be determined by film formation processes, such as surface diffusion or grain growth, which is affected by operating conditions. We also collected reported results about such PO-determining processes. Then, we categorized the PO-determining processes into an initial stage and a growth stage of film deposition, and further categorized each stage into a vapor–solid interface and a solid–solid interface. Then, we related each stage and interface to film morphology and to PO-determining processes. Finally, based on existing results, previous models, and proposed schema, we discuss the origin of PO. Based on previous experimental results on film morphology, PO of nitride films occurred in the growth stage at the vapor–solid interface, where the sticking process of the precursor and the surface diffusion process determine PO, rather than in the initial stage and in the growth stage at the solid–solid interface. TiN (002) PO, however, seems to be caused in the initial stage at the solid–solid interface.
Effect of an applied voltage during annealing on the resistivity and transparency of the amorphous tin oxide films
Authors: Parkansky N. , Alterkop B. , Goldsmith S. , Boxman R. L.
Published: November 2003

300 nm thick tin oxide thin films were deposited on glass by filtered vacuum arc deposition and annealed in air at 300 and 350 °C for up to 60 min. The resistivity of the coating before annealing was 3 mohm cm. During the annealing, an electric field E in the range of 0–200 V/cm was applied to the sample parallel to the film surface. As the sample was connected in series to a 5 kΩ resistor, the electric field on the sample was not constant during the annealing, depending on the variation of its resistance. The initial magnitude of the electric field on the sample was in the range of 0–17.4 V/cm. Film resistance decreased as function of short annealing times, reaching a minimum value after 1 to 3 min, and depended on the applied voltage U. At longer annealing times, the resistance continuously increased up to saturation after 8 min. The magnitude of the saturated resistance also depended on U, that is, on the field in the sample. The lowest electric resistivity (0.6 mohm cm) was obtained at 300 °C and U=100 V (initial field in sample of ∼9 V/cm). The minimum resistivity of annealed films without electric-field application was three times higher, 1.8 mohm cm. However, the minimal resistivity measured when U=200 V/cm (initial field 19.4 V/cm) was 2.1 mohm cm, i.e., larger by a factor of ∼1.2 than that obtained with no field. The visible transmittance, T, was measured before and after annealing, being 67% before annealing. The transmittance of annealed films depended on the annealing time and the applied field. The highest visible transmittance of films annealed with E=100 V/cm was 89%, and obtained after annealing for 5 min. The maximal visibility of films annealed with no field was 81%, and obtained after annealing for 8 min. The atomic ratio O/Sn on the film surface decreased linearly with time from ∼2 to ∼0.7 with U=100 V, but it remained greater than 1.3 at U=0 V. The O/Sn ratio remained approximately constant (∼2) at a depth larger than 20 nm.
Investigation of the role of plasma conditions on the deposition rate and electrochromic performance of tungsten oxide thin films
Authors: Seman Michael , Wolden Colin A.
Published: November 2003

Plasma-enhanced chemical vapor deposition has been used to form electrochromic tungsten oxide thin films from gas mixtures of WF6, O2, and H2. The chemistry of this system was investigated using optical emission spectroscopy. The plasma composition and deposition rate were examined as a function of operating conditions. Growth rates were maximized when the atomic fluorine density was attenuated and the atomic oxygen density was saturated. With the exception of hydrogen scavenging of fluorine radicals, the major reaction pathway was simply dissociation, as the densities of the atomic species were proportional to the initial reagent composition. An apparatus was built to evaluate electrochemical performance in direct registry with optical transmission. This characterization technique was used to demonstrate that ion bombardment has a dramatic impact on electrochromic performance. Ion bombardment was found to increase film density, as inferred from measurements of the refractive index. Efficient hydrogen intercalation was observed only in those films whose refractive index at 400 nm were less than 2.1. Finally, it was shown that a tungsten oxide thickness of ∼600 nm was optimal with respect to contrast ratio.
Effects of pretreatment on the performance of diamond-coated cemented carbide cutting tools
Authors: Wang Qiang , Zhang Qing , Wang S. G. , Yoon S. F. , Ahn J. , Zhao Biaoqin , Tang W. Z. , Miao J. Q. , Lu F. X.
Published: November 2003

We studied the cutting performance of diamond-coated cemented carbide cutting tools pretreated using acid etching, Murakami reagent etching, interlayer addition, and boronization techniques. The Rockwell indentation test indicates that the best adhesion is obtained from the diamond-coated cutting tool pretreated using boronization by forming a boronized cobalt compound layer composed of CoW2B2, CoWB, and CoB. The end-milling test shows that this sample exhibits the longest lifetime among diamond-coated cutting tools, 26-times longer than that of the uncoated cutting tool. The wearing mechanism of the cutting tools used is also discussed. During the milling period, the failure of the diamond-coated tool pretreated by boronization was dominated by how the diamond grains were gradually removed from the diamond coating by the workpiece scraps, instead of the peeling off of the diamond coating. This also reveals that the diamond coating exhibits good adhesion and cutting performance.
Characteristics of C4F8 plasmas with Ar, Ne, and He additives for SiO2 etching in an inductively coupled plasma (ICP) reactor
Authors: Li Xi , Ling Li , Hua Xuefeng , Oehrlein Gottlieb S. , Wang Yicheng , Anderson H. M.
Published: November 2003

We have characterized the effect of adding Ar, Ne, and He noble gases to C4F8 inductively coupled plasmas for SiO2 etching. The systematic variation of their ionization potentials, metastable energy levels, and mass of the dominant ion in C4F8/X% discharges (X=He, Ne, or Ar) containing a high percentage of the noble gas provides a means to evaluate the relative importance of gas phase and surface processes in the etching of SiO2. The total ion flux, ion composition, FC deposition and etching rates, and composition of the surface reaction layer formed on Si or SiO2 in these discharges show systematic differences as a function of process parameters because of the different electron impact ionization thresholds for Ar, Ne, and He gases, and differences in the mass of the dominant ion for discharges containing a large proportion of the noble gas. For given experimental conditions (600 W and 20 mTorr for most of this work), Ar addition gives rise to the largest ion current density, and He to the smallest ion current density. When the noble gases are added to C4F8, the Ar+ ion flux contributes the largest percentage and He+ the smallest percentage of the total ion flux for the same dilution of C4F8 with the noble gases. Ion compositional analysis shows that CF+, CF3+, and CF2+ are the dominant ionic fluorocarbon (FC) species (in order of importance), and that they show similar trends as a function of added Ar, Ne, and He percentage. The fluxes of the more highly dissociated C+, F+, and SiFx+/COFx+ ions are greater when Ne and He are added to C4F8 than for Ar addition. Ion energy distributions of all ions are displaced to lower energies for C4F8/Ar discharges as compared with C4F8/Ne or C4F8/He plasmas. Infrared laser absorption spectroscopy was used to determine absolute densities of neutral CF, CF2, and COF2 radical species as a function of gas composition. The densities of CF2 and COF2 radical species were enhanced when Ne and He were added to C4F8 in comparison to Ar addition. Fluorocarbon deposition rates on unbiased Si substrates were measured and greater for C4F8 discharges with Ne or He additives than when Ar was added. Upon rf biasing of the substrates, the ion energies required for etching to take place are lowest for C4F8/Ar discharges, followed by C4F8/He and C4F8/Ne discharges. A comparison of x-ray photoelectron spectra of SiO2 surfaces exposed to C4F8/X% discharges at −10 V self-bias voltage shows pronounced differences in the chemical bond distribution of fluorocarbon films which can be explained by differences in momentum transfer to the surface and the associated bond breaking of deposited fluorocarbon layers on the surface. A comparison of SiO2 and Si etching rates in C4F8/X% discharges shows that for C4F8/Ne discharges containing more than 70%Ne the highest SiO2/Si but lowest SiO2/resist etching rate ratio is obtained.
Measurement of the plasma potential adjacent to the substrate in a midfrequency bipolar pulsed magnetron
Authors: Karkari S. K. , Vetushka A. , Bradley J. W.
Published: November 2003

Using an emissive probe, the temporal evolution of plasma potential Vp in front of an electrically isolated substrate in an asymmetric pulsed dc magnetron has been determined. The discharge pulsing frequency was 100 kHz, with a 50% duty cycle. Through a scheme of externally biasing the emissive probe, it was found that the time response of the probe could be improved greatly, and a resolution of 20 ns was achieved. This good response revealed that Vp is highly modulated by the transient cathode potential, following it closely and varying from a value just above the ground potential in the pulse “on” phase, up to a value of +277 V during the positive overshoot in the “reverse” pulse phase. During the whole pulse cycle, Vp was found to remain above the most positive surface in the discharge. The results confirm our previous prediction for Vp, based on energy-resolved mass spectrometry [Bradley et al., Plasma Sources Sci. Technol. 11, 165 (2002)], which indicated that ions must be created at high positive plasma potentials. However, measurements here show that the substrate floating potential Vf is also strongly modulated and the difference Vp−Vf, which determines the ion bombarding energy, always remains below 40 V during steady phases of the discharge throughout the pulse cycle.
Stress analysis using anatomically realistic coronary tree
Authors: Wu Hsien‐Chih , Chen S.‐Y. James , Shroff Sanjeev G. , Carroll John D.
Published: November 2003

Plaque rupture with superimposed thrombosis is the main cause of the acute coronary syndromes of unstable angina, myocardial infarction, and sudden death. Endothelial disruption leading to plaque rupture may relate to mechanical fatigue associated with cyclic flexion of plaques. A novel method is proposed to assess stress and strain distribution using the finite element (FE) analysis and in vivo patient‐specific dynamic 3D coronary arterial tree reconstruction from cine angiographic images. The local stresses were calculated on the diseased arterial wall which was modeled as consisting of a central fibrotic cap subjected to the cyclic flexion from cardiac contraction. Various parameters characterizing the plaque were chosen including vessel diameter, percentage narrowing, and lesion length. According to the FEA simulations, the results show that the smaller vessel diameter, greater percentage narrowing, and/or larger lesion size may result in higher stress on the plaque cap, with the vessel diameter as the dominant factor.
A dose delivery verification method for conventional and intensity‐modulated radiation therapy using measured field fluence distributions
Authors: Renner Wendel Dean , Sarfaraz Mehrdad , Earl Matthew A. , Yu Cedric X.
Published: November 2003

Treatment verification has been a weak link in external beam radiation therapy. As new and more complicated treatment techniques, such as intensity‐modulated radiation therapy (IMRT), are implemented into clinical practice, verifying the accuracy of treatment delivery becomes increasingly important. Existing methods for treatment verification are highly labor intensive. We have developed a method for verifying the delivery of external beam radiotherapy and implemented the methodology into a system consisting of both hardware and software components. The system uses grayscale images acquired on the treatment machine from the planned treatment beams. From these images, the photon fluence distribution of each beam is derived. These measured photon fluence maps are then used as input to a separate dose calculation engine to compute the delivered absolute dose and the dose distribution in the same patient, assuming that the patient is set up as required by the treatment plan. The dose distribution generated from the measured fluence maps can then be compared to that of the treatment plan. Software tools, such as overlaying isodose curves generated with this method on those imported from the plan, dose difference maps, dose difference volume histograms, and three‐dimensional perspective views of the dose differences, have also been developed. The system thus provides a means to verify the dose, the dose prescription, and the monitor units applied. The potential exists with a suitable electronic portal imaging system to reduce the quality assurance efforts, especially for IMRT.
Visualization and analysis of electrodynamic behavior during cardiac arrhythmias
Authors: Bray Mark‐Anthony Peter
Published: November 2003

Sudden cardiac death is the primary cause of mortality in the industrialized world. Ventricular tachycardia and lethal arrhythmias such as ventricular fibrillation are believed to be the result of reentrant electrical activity, i.e., self‐sustained electrical activity which continues to re‐excite regions of cardiac tissue independently of the natural pacemaker rhythm. The mechanisms behind fibrillation initiation, maintenance, and termination by a defibrillatory shock are largely unknown. Cardiac fibrillation is characterized by a complex spatial interaction of nonstationary spiral waves; however, the nature of this interaction is an ongoing topic of investigation. The organizing center of reentry is a topological defect called a phase singularity in two dimensions, a filament in three dimensions; an understanding of fibrillation behavior may be obtained by localizing and tracking these defects. Experimentally, the electrodynamic behavior is typically investigated via optical mapping using voltage‐sensitive fluorescent dyes. In this thesis, a technique to detect phase singularities based upon topological charge was applied to nonlinear time‐series and phase portrait analysis of optical signals, and later extended to filament detection; this procedure was shown to be both efficient and mathematically robust. An alternate method to reconstruct the phase portrait was also explored and shown to overcome some of the limitations of the time‐series method as well as permitting singularity detection closer to initiation than previously allowed. Numerically examining the interaction dynamics of a simple filament configuration paralleling that seen in experimental preparations indicated that a critical bifurcation in filament lifetime exists between attractive and repulsive behavior along with annihilation by mutual collision and collapse by shrinkage, which could be represented by a difference of Yukawa potentials by treating the filaments as a pair of point charges. The inclusion of optical depth effects into a numerical model of three‐dimensional filament activity was studied, and suggested that these effects have a significant impact on observed epicardial activity. Finally, a three‐dimensional geometric reconstruction of an isolated, perfused heart with the fluorescence information as a texture map, previously developed as a proof‐of‐concept, was shown to be a viable tool for whole‐heart singularity visualization.
Fundamental image quality limits for microcomputed tomography in small animals
Authors: Ford N. L. , Thornton M. M. , Holdsworth D. W.
Published: November 2003

Small‐animal imaging has become increasingly more important as transgenic and knockout mice are produced to model human diseases. One imaging technique that has emerged is microcomputed tomography (micro‐CT). For live‐animal imaging, the precision in the images will be determined by the x‐ray dose given to the animal. As a result, we propose a simple method to predict the noise performance of an x‐ray micro‐CT system as a function of dose and image resolution. An ideal, quantum‐noise limited micro‐CT scanner, assumed to have perfect resolution and ideal efficiency, was modeled. Using a simplified model, the coefficient of variation (COV) of the linear attenuation coefficient was calculated for a range of entrance doses and isotropic voxel sizes. COV calculations were performed for the ideal case and with simulated imperfections in efficiency and resolution. Our model was validated in phantom studies and mouse images were acquired with a specimen scanner to illustrate the results. A simplified model of noise propagation in the case of isotropic resolution indicates that the COV in the linear attenuation coefficient is proportional to and to the in the reconstructed volume. Therefore an improvement in the precision can be achieved only by increasing the isotropic voxel size (thereby decreasing the resolution of the image) or by increasing the x‐ray dose. For the ideal scanner, a COV of 1% in the linear attenuation coefficient for an image of a mouse exposed to 0.25 Gy is obtained with a minimum isotropic voxel size of 135 μm. However, the same COV is achieved at a dose of 5.0 Gy with a 65 μm isotropic voxel size. Conversely, for a 68 mm diameter rat, a COV of 1% obtained from an image at 5.0 Gy would require an isotropic voxel size of 100 μm. These results indicate that short‐term, potentially lethal, effects of ionizing radiation will limit high‐resolution live animal imaging. As improvements in detector technology allow the resolution to improve, by decreasing the detector element size to tens of microns or less, high quality images will be limited by the x‐ray dose administered. For the highest quality images, these doses will approach the lethal dose or LD50 for the animals. Approaching the lethal dose will affect the way experiments are planned, and may reduce opportunities for experiments involving imaging the same animal over time. Dose considerations will become much more important for live small‐animal imaging as the limits of resolution are tested.
Independent verification of ultrasound based image‐guided radiation treatment, using electronic portal imaging and implanted gold markers
Authors: Van den Heuvel Frank , Powell Tanya , Seppi Edward , Littrupp Peter , Khan Mubashra , Wang Yue , Forman Jeffrey D.
Published: November 2003

The aim of this paper is to study the correction of prostate motion and position during external beam therapy. The correction was performed using a commercially available ultrasound‐based repositioning tool. Electronic portal imaging with the use of fiducial markers was used to assess efficacy and accuracy. Patients undergoing radiation treatment for adenocarcinoma of the prostate were enrolled in a positioning study. Fifteen patients had five to six gold fiducial markers implanted in their prostate. These patients were positioned daily in a standard manner and then were repositioned every other day using an ultrasound‐based correction system. Every fraction of a patients' treatment was imaged. This yielded 156 image pairs with and 119 pairs without repositioning available for analysis. This group of patients with markers had the following residual positions measured after the use of ultrasound repositioning. A mean error of −0.4 mm (LL), −2.6 mm (CC), and +2.5 mm (AP) with a standard deviation of 4.3, 5.4, and 5.7 mm. In two directions the improvements of treatment using the ultrasound correction were smaller than the precision of this experiment. They were no larger than 0.81 mm (LAT), and 0.95 mm (CC). In the AP direction a significant improvement was found of 1.6 mm. A highly significant correlation was found between the residual errors in the cranio‐caudal direction and the shifts performed on the basis of the ultrasound measurements (Spearman ranking We presented a method to objectively estimate improvements by a correction scheme. This method applied to ultrasound‐based adjustment showed significant improvement in one direction and no measurable improvement in two other directions.
Independent dosimetric calculation with inclusion of head scatter and MLC transmission for IMRT
Authors: Yang Y. , Xing L. , Li J. G. , Palta J. , Chen Y. , Luxton Gary , Boyer A.
Published: November 2003

Independent verification of the MU settings and dose calculation of IMRT treatment plans is an important step in the IMRT quality assurance (QA) procedure. At present, the verification is mainly based on experimental measurements, which are time consuming and labor intensive. Although a few simplified algorithms have recently been proposed for the independent dose (or MU) calculation, head scatter has not been precisely taken into account in all these investigations and the dose validation has mainly been limited to the central axis. In this work we developed an effective computer algorithm for IMRT MU and dose validation. The technique is superior to the currently available computer‐based MU check systems in that (1) it takes full consideration of the head scatter and leaf transmission effects; and (2) it allows a precise dose calculation at an arbitrary spatial point instead of merely a point on the central axis. In the algorithm the dose at an arbitrary spatial point is expressed as a summation of the contributions of primary and scatter radiation from all beamlets. Each beamlet is modulated by a dynamic modulation factor (DMF), which is determined by the MLC leaf trajectories, the head scatter, the jaw positions, and the MLC leaf transmission. A three‐source model was used to calculate the head scatter distribution for irregular segments shaped by MLC and the scatter dose contributions were computed using a modified Clarkson method. The system reads in MLC leaf sequence files (or RTP files) generated by the Corvus (NOMOS Corporation, Sewickley, PA) inverse planning system and then computes the doses at the desired points. The algorithm was applied to study the dose distributions of several testing intensity modulated fields and two multifield Corvus plans and the results were compared with Corvus plans and experimental measurements. The final dose calculations at most spatial points agreed with the experimental measurements to within 3% for both the specially designed testing fields and the clinical intensity modulated field. Furthermore, excellent agreement (mostly within ±3.0%) was also found between our independent calculation and the ion chamber measurements at both central axis and off‐axis positions for the multifield Corvus IMRT plans. These results indicate that the approach is robust and valuable for routine clinical IMRT plan validation.
Quantification of the effect of system and object parameters on edge enhancement in phase‐contrast radiography
Authors: Donnelly Edwin F. , Price Ronald R. , Pickens David R.
Published: November 2003

The purpose of this study was to evaluate the effects of system parameters (focal spot size, tube voltage, geometry, detector resolution, and image noise) and object characteristics (edge gradient/shape, composition, thickness, and overlying attenuating material) upon the edge enhancement effect in phase‐contrast radiography. Each variable of interest was adjusted and images of a 3 mm lucite phantom were obtained with the other variables remaining constant. A microfocus x‐ray source coupled to a CCD camera with an intensifying screen was used to acquire the digital images. Two parameters of image analysis were used to quantify the effects. The edge enhancement index (EEI) was used to measure the absolute degree of edge enhancement, while the edge enhancement to noise ratio (EE/N) was used to measure the conspicuity of the edge enhancement relative to image noise. Little effect on EEI was seen from tube voltage, object thickness, overlying attenuating material, while focal spot size and system geometry demonstrated measurable effects upon the degree of edge enhancement. It was also shown that while the edge enhancement effect over straight edges is highly dependent upon how the edge aligns with the x‐ray beam, rounded edges, which better model biological objects, do not suffer from this dependence and the EEI reaches its maximal level at any alignment. Decreasing detector resolution diminished the EEI slightly, but even with pixel sizes of 0.360×0.360 mm edge enhancement effects were readily visible. The effect of image noise on EE/N was evaluated using different exposure times showing an expected improvement with longer exposure time with EE/N approaching a plateau at 5 min. Many of the parameters that will go into the design of a future PC‐R imaging system have been quantified in terms of their effect on the degree of edge enhancement in the acquired image. These results, taken together, indicate that either a specimen or even clinical breast imaging system could be created with currently available technology. The major limitation to a clinical system would be the low x‐ray flux from the microfocal x‐ray source.
Matched view weighting in tilted‐plane‐based reconstruction algorithms to suppress helical artifacts and optimize noise characteristics
Authors: Tang Xiangyang
Published: November 2003

In multi‐slice helical CT, the single‐tilted‐plane‐based reconstruction algorithm has been proposed to combat helical and cone beam artifacts by tilting a reconstruction plane to fit a helical source trajectory optimally. Furthermore, to improve the noise characteristics or dose efficiency of the single‐tilted‐plane‐based reconstruction algorithm, the multi‐tilted‐plane‐based reconstruction algorithm has been proposed, in which the reconstruction plane deviates from the pose globally optimized due to an extra rotation along the 3rd axis. As a result, the capability of suppressing helical and cone beam artifacts in the multi‐tilted‐plane‐based reconstruction algorithm is compromised. A matched view weighting approach is proposed here to optimize the capability of suppressing helical and cone beam artifacts and noise characteristics. A helical body phantom is employed to quantitatively evaluate the imaging performance of the matched view weighting approach, showing that the matched view weighting improves both the helical artifact suppression and noise characteristics or dose efficiency significantly in comparison to the case in which nonmatched view weighting is applied. The matched view weighting approach is of practical importance in the development of multi‐slice helical CT, because it maintains the computational structure of fan beam filtered backprojection and demands no extra computational resources.
Real‐time inverse planning for Gamma Knife radiosurgery
Authors: Wu Q. Jackie , Chankong Vira , Jitprapaikulsarn Suradet , Wessels Barry W. , Einstein Douglas B. , Mathayomchan Boonyanit , Kinsella Timothy J.
Published: November 2003

The challenges of real‐time Gamma Knife™ inverse planning are the large number of variables involved and the unknown search space a priori. With limited collimator sizes, shots have to be heavily overlapped to form a smooth prescription isodose line that conforms to the irregular target shape. Such overlaps greatly influence the total number of shots per plan, making pre‐determination of the total number of shots impractical. However, this total number of shots usually defines the search space, a pre‐requisite for most of the optimization methods. Since each shot only covers part of the target, a collection of shots in different locations and various collimator sizes selected makes up the global dose distribution that conforms to the target. Hence, planning or placing these shots is a combinatorial optimization process that is computationally expensive by nature. We have previously developed a theory of shot placement and optimization based on skeletonization. The real‐time inverse planning process, reported in this paper, is an expansion and the clinical implementation of this theory. The complete planning process consists of two steps. The first step is to determine an optimal number of shots including locations and sizes and to assign initial collimator size to each of the shots. The second step is to fine‐tune the weights using a linear‐programming technique. The objective function is to minimize the total dose to the target boundary (i.e., maximize the dose conformity). Results of an ellipsoid test target and ten clinical cases are presented. The clinical cases are also compared with physician's manual plans. The target coverage is more than 99% for manual plans and 97% for all the inverse plans. The RTOG PITV conformity indices for the manual plans are between 1.16 and 3.46, compared to 1.36 to 2.4 for the inverse plans. All the inverse plans are generated in less than 2 min, making real‐time inverse planning a reality.
A method for modifying the image quality parameters of digital radiographic images
Authors: Saunders Robert S. , Samei Ehsan
Published: November 2003

A new computer simulation approach is presented that is capable of modeling several varieties of digital radiographic systems by their image quality characteristics. In this approach, the resolution and noise characteristics of ideal supersampled input images are modified according to input modulation transfer functions (MTFs) and noise power spectra (NPS). The modification process is separated into two routines—one for modification of the resolution and another for modification of the noise characteristics of the input image. The resolution modification routine blurs the input image by applying a frequency filter described by the input MTF. The resulting blurred image is then reduced to its final size to account for the sampling process of the digital system. The noise modification routine creates colored noise by filtering the frequency components of a white noise spectrum according to the input noise power. This noise is then applied to the image by a moving region of interest to account for variations in noise due to differences in attenuation. In order to evaluate the efficacy of the modification routines, additional routines were developed to assess the resolution and noise of digital images. The MTFs measured from the output images of the resolution modification routine were within 3% of the input MTF. The NPS measured from the output images of the noise modification routine were within 2% of the input NPS. The findings indicate that the developed modification routines provide a good means of simulating the resolution and noise characteristics of digital radiographic systems for optimization or processing purposes.
Multilaboratory Evaluation of a Viability Assay for Measurement of Opsonophagocytic Antibodies Specific to the Capsular Polysaccharides of
Streptococcus pneumoniae
Authors: Romero-Steiner Sandra , Frasch Carl , Concepcion Nelydia , Goldblatt David , Käyhty Helena , Väkeväinen Merja , Laferriere Craig , Wauters Dominique , Nahm Moon H. , Schinsky Mark F. , Plikaytis Brian D. , Carlone George M.
Published: November 2003

Opsonophagocytosis is a correlate of protection that measures the functional activity of vaccine-induced antibodies. A standardized opsonophagocytosis assay (OPA) should be used as part of the evaluation of current and future pneumococcal (Pnc) polysaccharide (Ps)-based vaccines. We enrolled five laboratories to evaluate a previously standardized viability OPA. Each laboratory was provided with a detailed OPA protocol, seven target Pnc strains (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F), two quality control sera and 12 paired sera (blinded) from adult donors who received one dose of the 23-valent Pnc Ps vaccine. Laboratories sent their results to the Centers for Disease Control and Prevention for analysis. Sera were tested in duplicate (single run), and the results were averaged to yield a single OPA titer (≥50% killing) for each serum sample. The percentage of sera within one or two dilutions of the calculated median OPA titer was determined for each laboratory and for each serotype. In general, laboratories were capable of detecting OPA titers within one or two dilutions of the median for at least 75 and 88%, respectively, of the sera tested. The level of agreement with the median OPA titers varied depending on the participating laboratory (overall agreement = 0.8 [99% confidence interval = 0.75 to 0.85]). All OPA median titers reported for quality control sera were within one dilution of the expected titer. We conclude that this OPA can be done in multiple laboratories with a high degree of interlaboratory reproducibility.
Relation between Seroreactivity to Low-Molecular-Weight
Helicobacter pylori
-Specific Antigens and Disease Presentation
Authors: Vilaichone Ratha-Korn , Mahachai Varocha , Kositchaiwat Chomsri , Graham David Y. , Yamaoka Yoshio
Published: November 2003

The identification of
Helicobacter pylori
-strain specific factors that correlate with clinical outcome has remained elusive. We investigated possible relationships between a group of
H. pylori
antigens and clinical outcome and compared an immunoblot assay kit (HelicoBlot, version 2.1 [HB 2.1]; Genelabs Diagnostics) with an established serological test, the high-molecular-weight cell-associated protein test (HM-CAP). We used sera from 156 Thai patients with different disease presentations, including 43 patients with gastric cancer, 64 patients with gastric ulcer, and 49 patients with nonulcer dyspepsia (NUD). HB 2.1 was compared to HM-CAP as a diagnostic test for
H. pylori
infection. The seroprevalence of
H. pylori
was significantly higher among gastric cancer patients than among patients with NUD (93 and 67%, respectively;
P
< 0.01). Among the
H. pylori
-seropositive patients, the presence of the antibody to the 37,000-molecular-weight antigen (37K antigen) was inversely related to the presence of gastric cancer (e.g., for gastric cancer patients compared with NUD patients, odds ratio [OR] = 0.28 and 95% confidence interval [CI] = 0.1 to 0.8). The presence of antibody to the 35K antigen was higher in gastric ulcer patients than in NUD patients (OR = 11.5; 95% CI = 2.4 to 54.3). The disease associations of antibodies to the 35K and 37K antigens are consistent with the possibility that these antigens are either indirect markers for
H. pylori
-related diseases or have specific active or protective roles in
H. pylori
-related diseases.
Immunoglobulin G and A Antibody Responses toBacteroides forsythusandPrevotella intermediain Sera and Synovial Fluids of Arthritis Patients
Authors: Moen Ketil , Brun Johan G. , Madland Tor Magne , Tynning Turid , Jonsson Roland
Published: November 2003

The objective of the present study was to investigate immunoglobulin G (IgG) and IgA antibody immune responses toPorphyromonas gingivalis,Prevotella intermedia,Bacteroides forsythus, andCandida albicansin the sera of patients with rheumatoid arthritis (RA), the synovial fluid (SF) of patients with RA (RA-SF samples), and the SF of patients without RA (non-RA-SF samples). An enzyme-linked immunosorbent assay was used to determine IgG and IgA antibody levels in 116 serum samples from patients with RA, 52 RA-SF samples, and 43 non-RA-SF samples; and these were compared with those in SF samples from 9 patients with osteoarthritis (OA-SF samples) and the blood from 100 donors (the control [CTR] group). Higher levels of IgG antibodies againstB. forsythus(P< 0.0001) andP. intermedia(P< 0.0001) were found in non-RA-SF samples than in OA-SF samples, and higher levels of IgG antibodies againstB. forsythus(P= 0.003) andP. intermedia(P= 0.024) were found in RA-SF samples than in OA-SF samples. Significantly higher levels of IgA antibodies againstB. forsythuswere demonstrated in both RA-SF and non-RA-SF samples than in OA-SF samples. When corrected for total Ig levels, levels of IgG antibody againstB. forsythuswere elevated in RA-SF and non-RA-SF samples compared to those in OA-SF samples. Lower levels of Ig antibodies againstB. forsythuswere found in the sera of patients with RA than in the plasma of the CTR group for both IgG (P= 0.003) and IgA (P< 0.0001). When corrected for total Ig levels, the levels of IgG and IgA antibodies againstB. forsythuswere still found to be lower in the sera from patients with RA than in the plasma of the CTR group (P< 0.0001). The levels of antibodies againstP. gingivalisandC. albicansin the sera and SF of RA and non-RA patients were comparable to those found in the respective controls. The levels of IgG and IgA antibodies againstB. forsythuswere elevated in SF from patients with RA and non-RA-SF samples compared to those in OA-SF samples. Significantly lower levels of IgG and IgA antibodies againstB. forsythuswere found in the sera of patients with RA than in the plasma of the CTR group. This indicates the presence of an active antibody response in synovial tissue and illustrates a potential connection between periodontal and joint diseases.
Analysis of the Shotgun Expression Library of the
Mycobacterium tuberculosis
Genome for Immunodominant Polypeptides: Potential Use in Serodiagnosis
Authors: Bisen Prakash S. , Garg Sanjay K. , Tiwari Ram P. , Tagore P. Ravindra Nath , Chandra Ramesh , Karnik Rucha , Thaker Nimesh , Desai Nirav , Ghosh P. K. , Fraziano Maurizio , Colizzi Vittorio
Published: November 2003

A recombinant DNA strategy was applied to analyze and screen the shotgun expression library from a clinically confirmed local virulent isolate of
Mycobacterium tuberculosis
with sera from tuberculosis patients, which led to expression and purification of highly immunoreactive and specific mycobacterial antigens expressed during the course of active disease which could be of diagnostic significance. An enzyme-linked immunoassay for diagnosis of tuberculosis was devised by using a shotgun immunoexpression library in the λgt11 vector. DNA from a virulent
M. tuberculosis
patient isolate (TBW-33) confirmed with the BACTEC 460 system was sheared and expressed to generate shotgun polypeptides. β-Galactosidase fusion proteins capable of demarcating active tuberculosis infections from
Mycobacterium bovis
BCG-vaccinated healthy subjects or people harboring environmental mycobacteria were selected by comparative immunoreactivity studies. Promising mycobacterial DNA cassettes were subcloned and expressed into the glutathione
S
-transferase (GST) fusion vector pGEX-5X-1 with a strong
tac
promoter and were expressed in
Escherichia coli
BL21. These fusion proteins were severed at a built-in factor Xa recognition site to separate the GST tags and were utilized in an indirect enzyme-linked immunoassay for serodiagnosis of patients with active tuberculosis. The system offered a clear demarcation between BCG-vaccinated healthy subjects and patients with active tuberculosis and proved to be effective in detecting pulmonary as well as extrapulmonary tuberculosis, with an overall sensitivity of 84.33% and an overall specificity of 93.62%.
Characterization of the Cytokine Immune Response in Children Who Have Experienced an Episode of Typical Hemolytic-Uremic Syndrome
Authors: Westerholt Soeren , Pieper Anne-Kathrin , Griebel Martin , Volk Hans-Dieter , Hartung Thomas , Oberhoffer Renate
Published: November 2003

The lipopolysaccharide (LPS) of enterohemorrhagic
Escherichia coli
(EHEC) and Shiga toxin together substantially contribute to the pathophysiology of typical hemolytic-uremic syndrome (HUS). Both factors have been shown to be immune stimulators and could play a key role in the individual innate immune response, characterized by proinflammatory and anti-inflammatory cytokines. By use of a whole blood stimulation model, we therefore compared the LPS- and superantigen-induced cytokine responses in children who had been having recovering from an acute episode of typical HUS for at least 6 months (group 1) with those in controls, who consisted of patients seen in the pediatric neurology outpatient department for routine examination (group 2). Samples were analyzed for cytokine protein levels and the levels of mRNA production. LPS stimulation revealed lower levels of interleukin 10 (IL-10) (
P
< 0.05) and increased levels of gamma interferon (
P
< 0.05) and increased ratios of pro- and anti-inflammatory cytokines (
P
< 0.05 for the IL-1β/IL-10 ratio;
P
< 0.05 for the tumor necrosis factor alpha/IL-10 ratio) in group 1. In addition superantigen stimulation showed decreased IL-2 levels in group 1 (
P
< 0.01). Our results suggest an alteration of the cytokine response characterized by high proinflammatory cytokine levels and low anti-inflammatory cytokine levels as well as low levels of IL-2 production in children who have experienced an episode of typical HUS. We hypothesize that this altered immune response is not a residual effect of the infection but a preexisting characteristic of the patient. This could be one reason why individuals infected with EHEC are potentially predisposed to a systemic disease (HUS).
Impairment by Mucosal Adjuvants and Cross-Reactivity with Variant Peptides of the Mucosal Immunity Induced by Injection of the Fusion Peptide PADRE-ELDKWA
Authors: Decroix Nipa , Pamonsinlapatham Perayot , Quan Cahn P. , Bouvet Jean-Pierre
Published: November 2003

Secretory immunity protects against mucosal transmission of viruses, as demonstrated with the oral poliovirus vaccine. In a previous study we showed that this immunity could be induced in mice by injection of a fusion peptide consisting of an unnatural peptide-like sequence (PADRE) and a viral epitope (ELDKWASLW). PADRE is a T-helper-cell epitope able to bind most major histocompatibility complex class II molecules of different haplotypes in mice and humans and to increase antibody responses. ELDKWA is a well-known consensual sequence of gp41 involved in a key structure of human immunodeficiency virus (HIV) type 1. Here, the antibody response to the native form of ELDKWA was mainly of the immunoglobulin A isotype and selectively occurred in mucosa. Adjuvants, such as cholera toxin and cytosine polyguanine, were useless and even competed with PADRE for the response. Interestingly, these antibodies were cross-reactive with the three major variants of the epitope, as shown both by direct enzyme-linked immunosorbent assay and by inhibition. This unconventional route of mucosal immunization allows control of the administered dose. The lack of adjuvant and the cross-reactivity of the antibodies increase the safety and the spectrum of the candidate vaccine, respectively. The drug-like nature of the construct suggests further improvements by synthesis of more antigenic sequences. The reasonable cost of short peptides at the industrial level and their purity make this approach of interest for future vaccines against mucosal transmission of HIV or other pathogens.
1,25-Dihydroxyvitamin D
3
and Development of Tuberculosis in Cattle
Authors: Rhodes S. G. , Terry L. A. , Hope J. , Hewinson R. G. , Vordermeier H. M.
Published: November 2003

This report describes the presence and activity of 1,25-dihydroxyvitamin D
3
(1,25-D
3
) in experimental bovine tuberculosis. Animals that went on to develop tuberculous lesions exhibited a rapid transient increase in serum 1,25-D
3
within the first 2 weeks following infection with
Mycobacterium bovis
. 1,25-D
3
-positive mononuclear cells were later identified in all tuberculous granulomas by immunohistochemical staining of postmortem lymph node tissue. These results suggest a role for 1,25-D
3
both at the onset of infection and in the development of the granuloma in these infected animals. Using a monoclonal antibody to the vitamin D receptor (VDR) as a VDR agonist, we confirmed that activation of the vitamin D pathway profoundly depresses antigen-specific, but not mitogenic, bovine peripheral blood T-cell responses (proliferation and gamma interferon production). Investigation of the mechanism of this suppression showed that the VDR antibody modified the expression of CD80 by accessory cells, such that a significant positive correlation between T-cell proliferation and accessory cell CD80 emerged.
Simplified Serological Diagnosis of Endocarditis Due toCoxiellaburnetiiandBartonella
Authors: Rolain J. M. , Lecam C. , Raoult D.
Published: November 2003

We tested a single-step serological assay againstCoxiellaburnetiiandBartonellaspecies and found a sensitivity of 100%, and a positive predictive value of 98% for the diagnosis of blood culture-negative endocarditis (BCNE). This assay should be considered as a possible commercial test for the diagnosis of BCNE.
Methemoglobinemia and Eccentrocytosis in Equine Erythrocyte Flavin Adenine Dinucleotide Deficiency
Authors: Harvey J. W. , Stockham S. L. , Scott M. A. , Johnson P. J. , Donald J. J. , Chandler C. J.
Published: November 2003

This report describes erythrocyte biochemical findings in an adult Spanish mustang mare that exhibited persistent methemoglobinemia, eccentrocytosis, and pyknocytosis that were not related to the consumption or administration of an exogenous oxidant. The methemoglobinemia was attributed to a deficiency in cytochrome-b5 reductase (Cb5R) activity, and the eccentrocytes and pyknocytes were attributed to a marked deficiency in reduced nicotinamide adenine dinucleotide phosphate—dependent glutathione reductase (GR) activity that resulted in decreased reduced glutathione concentration within erythrocytes. The GR activity increased to a near-normal value after addition of flavin adenine dinucleotide (FAD) to the enzyme assay, indicating a deficiency of FAD in erythrocytes. The methemoglobinemia, eccentrocytosis, and pyknocytosis were attributed to deficiency of FAD in erythrocytes because the GR and Cb5R enzymes use FAD as a cofactor. This deficiency in FAD results from a defect in erythrocyte riboflavin metabolism, which has not been documented previously in animals.