bluuebunny/crossref_metadata_2025 huggingface dataset:
Automatic detection of linear artifacts in medical images
Authors: Holupka E. J. , Meskell P. M. , Kaplan I. D.
Published: September 2004

Our purpose in this study is to describe an algorithm for the automatic detection of linear artifacts in medical images. Linear artifacts arise as a result of many different forms of tissues and tissue boundaries within the imaging volume. Additionally, linear artifacts can arise for artificial structures such as radioactive seeds and radioactive linear sources. It is the purpose of the described algorithm to automatically detect linear artifacts of a certain length and diameter. The algorithm was written and compiled on a Pentium‐4 based computer in the Microsoft Visual C/C++ language. Inert coils supplied by Radiomed Inc. were implanted into a standard prostate ultrasound phantom. Transaxial ultrasound images of the implanted phantom were obtained at 2 mm increments. The coded algorithm was then applied to the ultrasound imaging volume to automatically segment out the implanted coils. Thirteen coils were implanted in the prostate phantom. Thirteen coils were automatically identified in the imaging volume. An algorithm was developed to automatically determine the position and orientation of radioactive coils within an imaging volume. The algorithm successfully identified thirteen coils implanted in an ultrasound prostate phantom.
An investigation of accelerator head scatter and output factor in air
Authors: Ding George X.
Published: September 2004

Our purpose in this study was to investigate whether the Monte Carlo simulation can accurately predict output factors in air. Secondary goals were to study the head scatter components and investigate the collimator exchange effect. The Monte Carlo code, BEAMnrc, was used in the study. Photon beams of 6 and 18 MV were from a Varian Clinac 2100EX accelerator and the measurements were performed using an ionization chamber in a mini‐phantom. The Monte Carlo calculated in air output factors was within 1% of measured values. The simulation provided information of the origin and the magnitude of the collimator exchange effect. It was shown that the collimator backscatter to the beam monitor chamber played a significant role in the beam output factors. However the magnitude of the scattered dose contributions from the collimator at the isocenter is negligible. The maximum scattered dose contribution from the collimators was about 0.15% and 0.4% of the total dose at the isocenter for a 6 and 18 MV beam, respectively. The scattered dose contributions from the flattening filter at the isocenter were about 0.9–3% and 0.2–6% of the total dose for field sizes of for the 6 and 18 MV beam, respectively. The study suggests that measurements of head scatter factors be done at large depth well beyond the depth of electron contamination. The insight information may have some implications for developing generalized empirical models to calculate the head scatter.
Patient dose in digital mammography
Authors: Chevalier Margarita , Morán Pilar , Ten José I. , Fernández Soto José M. , Cepeda T. , Vañó Eliseo
Published: September 2004

In the present investigation, we analyze the dose of 5034 patients (20 137 images) who underwent mammographic examinations with a full‐field digital mammography system. Also, we evaluate the system calibration by analyzing the exposure factors as a function of breast thickness. The information relevant to this study has been extracted from the image DICOM header and stored in a database during a 3‐year period (March 2001–October 2003). Patient data included age, breast thickness, kVp, mAs, target/filter combination, and nominal dose values. Entrance surface air kerma (ESAK) without backscatter was calculated from the tube output as measured for each voltage used under clinical conditions and from the tube loading (mAs) included in the DICOM header. Mean values for the patient age and compressed breast thickness were 56 years (SD: 11) and 52 mm (SD: 13), respectively. The majority of the images was acquired using the STD (for standard) automatic mode (98%). The most frequent target/filter combination automatically selected for breast smaller than 35 mm was Mo/Mo (75%); for intermediate thicknesses between 35 and 65 mm, the combinations were Mo/Rh (54%) and Rh/Rh (38.5%); Rh/Rh was the combination selected for 91% of the cases for breasts thicker than 65 mm. A wide kVp range was observed for each target/filter combination. The most frequent values were 28 kVp for Mo/Mo, 29 kVp for Mo/Rh, and 29 and 30 kV for Rh/Rh. Exposure times ranged from 0.2 to 4.2 s with a mean value of 1.1 s. Average glandular doses (AGD) per exposure were calculated by multiplying the ESAK values by the conversion factors tabulated by Dance for women in the age groups 50 to 64 and 40 to 49. This approach is based on the dependence of breast glandularity on breast thickness and age. The total mean average glandular dose was calculated by summing the values associated with the pre‐exposure and with the main exposure. Mean per exposure was 1.88 mGy (CI 0.01) and the mean per examination was 3.8 mGy, with 4 images per examination on average. The mean dose for cranio‐caudal view (CC) images was 1.8 mGy, which is lower than that for medio‐lateral oblique (MLO) view because the thickness for CC images was on average 10% lower than that for MLO images. Mean for the oldest group of women (1.90) was 3% higher than the for the younger group (1.85) due to the larger compressed breast thickness of women in the older group (10% on average). Differences between the corresponding values of each age group were lowest for breast thicknesses in the range 40–60 mm, being slightly higher for the women in the older group.
Incorporating model parameter uncertainty into inverse treatment planning
Authors: Lian Jun , Xing Lei
Published: September 2004

Radiobiological treatment planning depends not only on the accuracy of the models describing the dose‐response relation of different tumors and normal tissues but also on the accuracy of tissue specific radiobiological parameters in these models. Whereas the general formalism remains the same, different sets of model parameters lead to different solutions and thus critically determine the final plan. Here we describe an inverse planning formalism with inclusion of model parameter uncertainties. This is made possible by using a statistical analysis‐based frameset developed by our group. In this formalism, the uncertainties of model parameters, such as the parameter a that describes tissue‐specific effect in the equivalent uniform dose (EUD) model, are expressed by probability density function and are included in the dose optimization process. We found that the final solution strongly depends on distribution functions of the model parameters. Considering that currently available models for computing biological effects of radiation are simplistic, and the clinical data used to derive the models are sparse and of questionable quality, the proposed technique provides us with an effective tool to minimize the effect caused by the uncertainties in a statistical sense. With the incorporation of the uncertainties, the technique has potential for us to maximally utilize the available radiobiology knowledge for better IMRT treatment.
Comparison study of MOSFET detectors and diodes for entrance in vivo dosimetry in 18 MV x‐ray beams
Authors: Jornet N. , Carrasco P. , Jurado D. , Ruiz A. , Eudaldo T. , Ribas M.
Published: September 2004

The feasibility of dual bias dual metal oxide semiconductor field effect transistors (MOSFETs) for entrance in vivo dose measurements in high energy x‐rays beams (18 MV) was investigated. A comparison with commercially available diodes for in vivo dosimetry for the same energy range was performed. As MOSFETs are sold without an integrated build‐up cap, different caps were tested: 3 cm bolus, 2 cm bolus, 2 cm hemispherical cap of a water equivalent material (Plastic Water™) and a metallic hemispherical cap. This metallic build‐up cap is the same as the one that is mounted on the in vivo diode used in this study. Intrinsic precision and response linearity with dose were determined for MOSFETs and diodes. They were then calibrated for entrance in vivo dosimetry in an 18 MV x‐ray beam. Calibration included determination of the calibration factor in standard reference conditions and of the correction factors (CF) when irradiation conditions differed from those of reference. Correction factors for field size, source surface distance, wedge, and temperature were determined. Sensitivity variation with accumulated dose and the lifetime of both types of detectors were also studied. Finally, the uncertainties of entrance in vivo measurements using MOSFET and diodes were discussed. Intrinsic precision for MOSFETs for the high sensitivity mode was 0.7% (1 s.d.) as compared to the 0.05% (1 s.d.) for the studied diodes. The linearity of the response with dose was excellent for both in vivo dosimetry systems. The absolute values of the studied correction factors for the MOSFETs when covered by the different build‐up caps were of the same order of those determined for the diodes. However, the uncertainties of the correction factors for MOSFETs were significantly higher than for diodes. Although the intrinsic precision and the uncertainty on the CF was higher for MOSFET detectors than for the studied diodes, the total uncertainty in entrance dose determination, once they were calibrated, was of 2.9% (1 s.d.) while for diodes it was 2.0% (1 s.d.). MOSFETs showed no sensitivity variation with accumulated dose or temperature. When used in the high sensitivity mode, after approximately 50 Gy of accumulated dose MOSFETs could no longer be used as radiation dosimeters. In conclusion, MOSFETs can be used for entrance in vivo dosimetry in high energy x‐rays beams if covered by an appropriate build‐up cap. Metallic build‐up caps, such as those used for in vivo diodes, have the advantage of greater patient comfort and less perturbation of the treatment field than the other build‐up caps tested, while keeping the correction factors of the same order.
Dose uncertainty due to computed tomography (CT) slice thickness in CT‐based high dose rate brachytherapy of the prostate cancer
Authors: Kim Yongbok , Hsu I‐Chow Joe , Lessard Etienne , Pouliot Jean , Vujic Jasmina
Published: September 2004

In computed tomography (CT)‐based high dose rate (HDR) brachytherapy, the uncertainty in the localization of the longitudinal catheter‐tip positions due to the discrete CT slice thickness, results in a delivered dose uncertainty. Catheter coordinates were extracted from five patients treated for prostate cancer, and three simulation scenarios were followed to mimic the longitudinal imprecision of the catheter tips, hence the dwell positions. All catheters were displaced (1) forward, (2) backward, or (3) randomly distributed within the space defined by one CT slice thickness, for thicknesses ranging from 2 to 5 mm. Average and standard deviation values of the relative dose variations are reported for the various catheter displacement scenarios. Also, the dose points were grouped according to their relative position in the prostate, inner, peripheral and outer area of prostate and base, median and apex zones, in order to estimate the spatial sensitivity of the dose errors. For scenarios (1) and (2), the dose uncertainties due to the finite slice thickness increase linearly with the slice spacing, from 3% to 8% for the slice thickness values ranging from 2 to 5 mm, respectively. The more realistic scenario (3) yields average errors ranging from 0.7% to 1.7%. The apex and the base show larger dose errors and variability of dose errors than the median of the prostate. No statistical difference was observed among different transversal sections of the prostate. A CT slice thickness of 3 mm appears to be a good compromise showing an acceptable average dose uncertainty of 1%, without unduly increasing the number of slices.
Characteristics relevant to portal dosimetry of a cooled CCD camera‐based EPID
Authors: Franken E. M. , de Boer J. C. J. , Barnhoorn J. C. , Heijmen B. J. M.
Published: September 2004

Our EPIDs have recently been equipped with Peltier‐cooled CCD cameras. The CCD cooling dramatically reduced deteriorating effects of radiation damage on image quality. Over more than 600 days of clinical operation, the radiation induced noise contribution has remained stable at a very low level (1 SD⩽0.15% of the camera dynamic range), in marked contrast with the previously used noncooled cameras. The camera response (output signal versus incident EPID radiation exposure) can be accurately described with a quadratic function. This response reproduced well, both in short and long term (variation <0.2% respectively <0.4% (1 SD)), rendering the cooled camera well‐suited for EPID dosimetry applications.
An inverse‐geometry volumetric CT system with a large‐area scanned source: A feasibility study
Authors: Schmidt Taly Gilat , Fahrig Rebecca , Pelc Norbert J. , Solomon Edward G.
Published: September 2004

We propose an inverse‐geometry volumetric CT system for acquiring a 15‐cm volume in one rotation with negligible cone‐beam artifacts. The system uses a large‐area scanned source and a smaller detector array. This note describes two feasibility investigations. The first examines data sufficiency in the transverse planes. The second predicts the signal‐to‐noise ratio (SNR) compared to a conventional scanner. Results showed sufficient sampling of the full volume in less than 0.5 s and, when compared to a conventional scanner operating at 24 kW with a 0.5‐s voxel illumination time (e.g., 0.5‐s gantry rotation and pitch of one), predicted a relative SNR of 76%.
Modelling of metastatic cure after radionuclide therapy: Influence of tumor distribution, cross‐irradiation, and variable activity concentration
Authors: Bernhardt Peter , Ahlman Hakan , Forssell‐Aronsson Eva
Published: September 2004

The objective was to study the influence of tumor number and size, cross‐irradiation from normal tissue, and of variable activity concentration on metastatic cure after radionuclide therapy. A model to calculate the metastatic cure probability (MCP) was developed, in which it was assumed that the tumor response was an exponential function of the absorbed dose. All calculations were performed for monoenergetic electron emitters with different energies (10–1000 keV). The influence of tumor size and number of tumors were investigated with different log uniform distributions; the basic tumor distribution consisted of tumors with cells. The influence of cross‐irradiation was assessed by calculating MCP for various tumor‐to‐normal tissue activity concentration ratios (TNC). The influence of variable activity concentration between tumors was calculated by assuming that the activity concentration in tumors was an inverse power law function of tumor mass. The required activity concentration and absorbed dose to obtain was calculated in the different models. The and needed to obtain MCP were very high; more than 25 MBq/g and 80 Gy, respectively. The lowest and for equal activity concentration in the different tumor sizes were obtained for electron energies less than 80 keV. For higher energies the low absorbed energy fraction in small tumors will increase the required and markedly. Cross‐irradiation from normal cells surrounding the tumor will cause sterilization of the smallest tumors and decrease the required and for higher electron energies. Assuming that the activity concentration decreased with increased tumor mass caused a marked increase in and in favor of higher electron energies. With the MCP model we demonstrated significant influence of the number of tumors, their size, TNC and variable activity concentration on MCP. The results are valuable when evaluating optimal choices for radionuclides for internal‐emitter therapy.
Implementation of the DPM Monte Carlo code on a parallel architecture for treatment planning applications
Authors: Tyagi Neelam , Bose Abhijit , Chetty Indrin J.
Published: September 2004

We have parallelized the Dose Planning Method (DPM), a Monte Carlo code optimized for radiotherapy class problems, on distributed‐memory processor architectures using the Message Passing Interface (MPI). Parallelization has been investigated on a variety of parallel computing architectures at the University of Michigan‐Center for Advanced Computing, with respect to efficiency and speedup as a function of the number of processors. We have integrated the parallel pseudo random number generator from the Scalable Parallel Pseudo‐Random Number Generator (SPRNG) library to run with the parallel DPM. The Intel cluster consisting of 800 MHz Intel Pentium III processor shows an almost linear speedup up to 32 processors for simulating or more particles. The speedup results are nearly linear on an Athlon cluster (up to 24 processors based on availability) which consists of Advanced Micro Devices (AMD) Athlon processors on increasing the problem size up to histories. For a smaller number of histories the reduction of efficiency with the Athlon cluster (down to 83.9% with 24 processors) occurs because the processing time required to simulate histories is less than the time associated with interprocessor communication. A similar trend was seen with the Opteron Cluster (consisting of 1400 MHz, 64‐bit AMD Opteron processors) on increasing the problem size. Because of the 64‐bit architecture Opteron processors are capable of storing and processing instructions at a faster rate and hence are faster as compared to the 32‐bit Athlon processors. We have validated our implementation with an in‐phantom dose calculation study using a parallel pencil monoenergetic electron beam of 20 MeV energy. The phantom consists of layers of water, lung, bone, aluminum, and titanium. The agreement in the central axis depth dose curves and profiles at different depths shows that the serial and parallel codes are equivalent in accuracy.
A comparison of reconstruction algorithms for breast tomosynthesis
Authors: Wu Tao , Moore Richard H. , Rafferty Elizabeth A. , Kopans Daniel B.
Published: September 2004

Three algorithms for breast tomosynthesis reconstruction were compared in this paper, including (1) a back‐projection (BP) algorithm (equivalent to the shift‐and‐add algorithm), (2) a Feldkamp filtered back‐projection (FBP) algorithm, and (3) an iterative Maximum Likelihood (ML) algorithm. Our breast tomosynthesis system acquires 11 low‐dose projections over a 50° angular range using an (CsI:Tl) flat‐panel detector. The detector was stationary during the acquisition. Quality metrics such as signal difference to noise ratio (SDNR) and artifact spread function (ASF) were used for quantitative evaluation of tomosynthesis reconstructions. The results of the quantitative evaluation were in good agreement with the results of the qualitative assessment. In patient imaging, the superimposed breast tissues observed in two‐dimensional (2D) mammograms were separated in tomosynthesis reconstructions by all three algorithms. It was shown in both phantom imaging and patient imaging that the BP algorithm provided the best SDNR for low‐contrast masses but the conspicuity of the feature details was limited by interplane artifacts; the FBP algorithm provided the highest edge sharpness for microcalcifications but the quality of masses was poor; the information of both the masses and the microcalcifications were well restored with balanced quality by the ML algorithm, superior to the results from the other two algorithms.
Methanobactin, a Copper-Acquisition Compound from Methane-Oxidizing Bacteria
Authors: Kim Hyung J. , Graham David W. , DiSpirito Alan A. , Alterman Michail A. , Galeva Nadezhda , Larive Cynthia K. , Asunskis Dan , Sherwood Peter M. A.
Published: September 2004

Siderophores are extracellular iron-binding compounds that mediate iron transport into many cells. We present evidence of analogous molecules for copper transport from methane-oxidizing bacteria, represented here by a small fluorescent chromopeptide (C
45
N
12
O
14
H
62
Cu, 1216 daltons) produced by
Methylosinus trichosporium
OB3b. The crystal structure of this compound, methanobactin, was resolved to 1.15 angstroms. It is composed of a tetrapeptide, a tripeptide, and several unusual moieties, including two 4-thionyl-5-hydroxy-imidazole chromophores that coordinate the copper, a pyrrolidine that confers a bend in the overall chain, and an amino
-
terminal isopropylester group. The copper coordination environment includes a dual nitrogen- and sulfur-donating system derived from the thionyl imidazolate moieties. Structural elucidation of this molecule has broad implications in terms of organo-copper chemistry, biological methane oxidation, and global carbon cycling.
Advanced Cardiac Morphogenesis Does Not Require Heart Tube Fusion
Authors: Li Shanru , Zhou Deying , Lu Min Min , Morrisey Edward E.
Published: September 2004

The bilateral cardiac mesoderm migrates from the lateral region of the embryo to the ventral midline, where it fuses to form the primitive heart tube. It is generally accepted that migration and fusion are essential for subsequent stages of cardiac morphogenesis. We present evidence that, in
Foxp4
mutant embryonic mice, each bilateral heart-forming region is capable of developing into a highly differentiated four-chambered mammalian heart in the absence of midline fusion. These data demonstrate that left-right chamber specification, cardiac looping, septation, cardiac myocyte differentiation, and endocardial cushion formation are preprogrammed in the precardiac mesoderm and do not require midline positional identity or heart tube fusion.
The Value of Things to Come
Authors: Grasso Domenico
Published: September 2004

Human-Built World
How to Think about Technology and Culture. Thomas P. Hughes. University of Chicago Press, Chicago, 2004. 235 pp. $22.50, £16. ISBN 0-226-35933-6.

In discussions that stress that technology is far more than gadgetry, Hughes draws on history, art, literature, and architecture to explore the complex and varied nature of technology.
Iron-Source Preference of
Staphylococcus aureus
Infections
Authors: Skaar Eric P. , Humayun Munir , Bae Taeok , DeBord Kristin L. , Schneewind Olaf
Published: September 2004

Although bacteria use different iron compounds in vitGro, the possibility that microbes distinguish between these iron sources during infection has hitherto not been examined. We applied stable isotope labeling to detect source-specific iron by mass spectrometry and show that
Staphylococcus aureus
preferentially imports heme iron over transferrin iron. By combining this approach with computational genome analysis, we identified
hts
(heme transport system), a gene cluster that promotes preferred heme iron import by
S. aureus
. Heme iron scavenging by means of
hts
is required for staphylococcal pathogenesis in animal hosts, indicating that heme iron is the preferred iron source during the initiation of infection.
Activation of Endogenous Cdc42 Visualized in Living Cells
Authors: Nalbant Perihan , Hodgson Louis , Kraynov Vadim , Toutchkine Alexei , Hahn Klaus M.
Published: September 2004

Signaling proteins are tightly regulated spatially and temporally to perform multiple functions. For Cdc42 and other guanosine triphosphatases, the subcellular location of activation is a critical determinant of cell behavior. However, current approaches are limited in their ability to examine the dynamics of Cdc42 activity in living cells. We report the development of a biosensor capable of visualizing the changing activation of endogenous, unlabeled Cdc42 in living cells. With the use of a dye that reports protein interactions, the biosensor revealed localized activation in the trans-Golgi apparatus, microtubule-dependent Cdc42 activation at the cell periphery, and activation kinetics precisely coordinated with cell extension and retraction.
Experimental Observation of Nonlinear Traveling Waves in Turbulent Pipe Flow
Authors: Hof Björn , van Doorne Casimir W. H. , Westerweel Jerry , Nieuwstadt Frans T. M. , Faisst Holger , Eckhardt Bruno , Wedin Hakan , Kerswell Richard R. , Waleffe Fabian
Published: September 2004

Transition to turbulence in pipe flow is one of the most fundamental and longest-standing problems in fluid dynamics. Stability theory suggests that the flow remains laminar for all flow rates, but in practice pipe flow becomes turbulent even at moderate speeds. This transition drastically affects the transport efficiency of mass, momentum, and heat. On the basis of the recent discovery of unstable traveling waves in computational studies of the Navier-Stokes equations and ideas from dynamical systems theory, a model for the transition process has been suggested. We report experimental observation of these traveling waves in pipe flow, confirming the proposed transition scenario and suggesting that the dynamics associated with these unstable states may indeed capture the nature of fluid turbulence.
Asymmetric Cochlear Processing Mimics Hemispheric Specialization
Authors: Sininger Y. S. , Cone-Wesson B.
Published: September 2004

Otoacoustic emissions or OAEs (reflections of cochlear energy produced during the processing of sound) were measured in response to two types of stimuli, rapid clicks and sustained tones, in each ear of neonates. OAEs were larger to tones when elicited in the left ear and to clicks when elicited in the right. This finding is similar to those of enhanced processing of tones in right auditory cortical areas and of rapid stimuli on the left, given strong crossed connections from ear to brain. These findings indicate that processing at the level of the ear may facilitate lateralization of auditory function in the brain.
Building Circuits of Trust
Authors: Hong Sungook
Published: September 2004

The Morals of Measurement
Accuracy, Irony, and Trust in Late Victorian Electrical Practice. Graeme J. N. Gooday. Cambridge University Press, Cambridge, 2004. 357 pp. $85, £55.00. ISBN 0-521-43098-4.

The author offers a social history of electrical technology that focuses on the questions of how electricity was to be quantified and who was qualified to make the required measurements.
Mesophase Structure-Mechanical and Ionic Transport Correlations in Extended Amphiphilic Dendrons
Authors: Cho B.-K. , Jain A. , Gruner S. M. , Wiesner U.
Published: September 2004

We have studied the self-assembly of amphiphilic dendrons extended with linear polyethylene oxide (PEO) chains and their ion complexes. Keeping the dendron core and linear PEO chain compatible allows for the combination of dendritic core-shell and conventional blockcopolymer characteristics for complex mesophase behavior. An unexpected sequence of crystalline lamellar, cubic micellar (

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), hexagonal columnar, continuous cubic (

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), and lamellar mesophases is observed. Multiple phase behavior within single compounds allows for the study of charge transport and mechanical property correlations as a function of structure. The results suggest an advanced molecular design concept for the next generation of nanostructured materials in applications involving charge transport.
Climate Impact on Plankton Ecosystems in the Northeast Atlantic
Authors: Richardson Anthony J. , Schoeman David S.
Published: September 2004

It is now widely accepted that global warming is occurring, yet its effects on the world's largest ecosystem, the marine pelagic realm, are largely unknown. We show that sea surface warming in the Northeast Atlantic is accompanied by increasing phytoplankton abundance in cooler regions and decreasing phytoplankton abundance in warmer regions. This impact propagates up the food web (bottom-up control) through copepod herbivores to zooplankton carnivores because of tight trophic coupling. Future warming is therefore likely to alter the spatial distribution of primary and secondary pelagic production, affecting ecosystem services and placing additional stress on already-depleted fish and mammal populations.
Species Coextinctions and the Biodiversity Crisis
Authors: Koh Lian Pin , Dunn Robert R. , Sodhi Navjot S. , Colwell Robert K. , Proctor Heather C. , Smith Vincent S.
Published: September 2004

To assess the coextinction of species (the loss of a species upon the loss of another), we present a probabilistic model, scaled with empirical data. The model examines the relationship between coextinction levels (proportion of species extinct) of affiliates and their hosts across a wide range of coevolved interspecific systems: pollinating
Ficus
wasps and
Ficus
, parasites and their hosts, butterflies and their larval host plants, and ant butterflies and their host ants. Applying a nomographic method based on mean host specificity (number of host species per affiliate species), we estimate that 6300 affiliate species are “coendangered” with host species currently listed as endangered. Current extinction estimates need to be recalibrated by taking species coextinctions into account.
Hydrophobic Collapse in Multidomain Protein Folding
Authors: Zhou Ruhong , Huang Xuhui , Margulis Claudio J. , Berne Bruce J.
Published: September 2004

We performed molecular dynamics simulations of the collapse of a two-domain protein, the BphC enzyme, into a globular structure to examine how water molecules mediate hydrophobic collapse of proteins. In the interdomain region, liquid water persists with a density 10to 15% lower than in the bulk, even at small domain separations. Water depletion and hydrophobic collapse occur on a nanosecond time scale, which is two orders of magnitude slower than that found in the collapse of idealized paraffin-like plates. When the electrostatic protein-water forces are turned off, a dewetting transition occurs in the interdomain region and the collapse speeds up by more than an order of magnitude. When attractive van der Waals forces are turned off as well, the dewetting in the interdomain region is more profound, and the collapse is even faster.
Mechanism of Ammonia Transport by Amt/MEP/Rh: Structure of AmtB at 1.35 Å
Authors: Khademi Shahram , O'Connell Joseph , Remis Jonathan , Robles-Colmenares Yaneth , Miercke Larry J. W. , Stroud Robert M.
Published: September 2004

The first structure of an ammonia channel from the Amt/MEP/Rh protein superfamily, determined to 1.35 angstrom resolution, shows it to be a channel that spans the membrane 11 times. Two structurally similar halves span the membrane with opposite polarity. Structures with and without ammonia or methyl ammonia show a vestibule that recruits NH
4
+
/NH
3
, a binding site for NH
4
+
, and a 20 angstrom–long hydrophobic channel that lowers the NH
4
+
p
K
a
to below 6 and conducts NH
3
. Favorable interactions for NH
3
are seen within the channel and use conserved histidines. Reconstitution of AmtB into vesicles shows that AmtB conducts uncharged NH
3
.
Interleukin 8 Secretion from Monocytes of Subjects Heterozygous for the ΔF508 Cystic Fibrosis Transmembrane Conductance Regulator Gene Mutation Is Altered
Authors: Zaman Munir M. , Gelrud Andres , Junaidi Omer , Regan Meredith M. , Warny Michel , Shea Julie C. , Kelly Ciaran , O'Sullivan Brian P. , Freedman Steven D.
Published: September 2004

Patients with cystic fibrosis (CF) exhibit an excessive host inflammatory response. The aim of this study was to determine (i) whether interleukin 8 (IL-8) secretion is increased from monocytes from subjects heterozygous as well as homozygous for cystic fibrosis transmembrane conductance regulator (CFTR) mutations and (ii) whether this is due to increased cell surface lipopolysaccharide (LPS) receptors or, alternatively, increased activation of mitogen-activated protein kinases (MAPK). The basal level of IL-8 secretion was higher from monocytes from CF patients than from monocytes from healthy controls (
P
= 0.02) and obligate heterozygotes (parents of the CF patients). The 50% effective concentrations for LPS-induced IL-8 production for monocytes from both CF patients and obligate heterozygotes were 100-fold lower than those for monocytes from healthy controls (
P
< 0.05). No differences in the levels of IL-1β production were seen between these groups. Expression of the LPS surface receptors CD14 and Toll-like receptor 4 were not different between CF patients and healthy controls. In contrast, phosphorylation of the MAPKs p38 and ERK occurred at lower doses of LPS in monocytes from patients heterozygous and homozygous for CFTR mutations. These results indicate that a single allelic CFTR mutation is sufficient to augment IL-8 secretion in response to LPS. This is not a result of increased LPS receptor expression but, rather, is associated with alterations in MAPK signaling.
Serological Response to
Pasteurella multocida
NanH Sialidase in Persistently Colonized Rabbits
Authors: Sanchez Susan , Mizan Shaikh , Quist Charlotte , Schroder Patricia , Juneau Michelle , Dawe Donald , Ritchie Branson , Lee Margie D.
Published: September 2004

Pasteurella multocida
is a mucosal pathogen that colonizes the upper respiratory system of rabbits. Respiratory infections can result, but the bacteria can also invade the circulatory system, producing abscesses or septicemia.
P. multocida
produces extracellular sialidase activity, which is believed to augment colonization of the respiratory tract and the production of lesions in an active infection. Previously, it was demonstrated that some isolates of
P. multocida
contain two unique sialidase genes,
nanH
and
nanB
, that encode enzymes with different substrate specificities (S. Mizan, A. D. Henk, A. Stallings, M. Meier, J. J. Maurer, and M. D. Lee, J. Bacteriol. 182:6874-6883, 2000). We developed a recombinant antigen enzyme-linked immunosorbent assay (ELISA) based on the NanH sialidase of
P. multocida
and demonstrated that rabbits that were experimentally colonized with
P. multocida
produce detectable anti-NanH immunoglobulin M (IgM) and IgG in serum, although they demonstrated no clinical signs of pasteurellosis. In addition, clinically ill pet rabbits infected with
P. multocida
possessed IgM and/or IgG antibody against NanH. The NanH ELISA may be useful for the diagnosis of
P. multocida
infections in sick rabbits as well as for screening for carriers in research rabbit colonies.
Regeneration and Tolerance Factor Prevents Bystander T-Cell Death Associated with Human Immunodeficiency Virus Infection
Authors: Derks Richard A. , Beaman Kenneth D.
Published: September 2004

Human immunodeficiency virus (HIV) infection is characterized by a depletion of T cells. This depletion is caused both by the virus-induced death of infected T cells and by the death of uninfected cells (bystander depletion) by a mechanism which is largely uncharacterized. Regeneration and tolerance factor (RTF) is a subunit of the vacuolar ATPase and a protein that is involved with activation and apoptosis. Anti-RTF antibodies mediate apoptosis in T lymphocytes. When anti-RTF was added to lymphocytes from an HIV-positive individual, they underwent larger amounts of apoptosis than cells taken from healthy controls. When lymphocytes were examined by Western blotting, those from HIV-positive individuals exhibited increased levels of expression of the 50-kDa protein (P< 0.001). A 70-kDa protein was the predominant form of RTF in uninfected control lymphocytes, being expressed in 100% of individuals studied. The expression of the 50-kDa protein in HIV-positive individuals correlated with decreased absolute CD4 counts with a sensitivity of 92% and a positive predictive value of 86%. When uninfected lymphocytes were stimulated with anti-CD3 and anti-CD28, no RTF was detected during early stimulation but a 50-kDa protein was expressed during late stimulation. When the susceptibilities of the lymphocytes to anti-RTF-induced apoptosis were measured, they correlated with the size of the RTF protein expressed. The cells were not susceptible to apoptosis when the 70-kDa RTF was present but were susceptible when the 50-kDa RTF was present. We propose that the increase in the levels of the 50-kDa RTF on cells from HIV-positive individuals is important in preventing the cell from undergoing apoptosis.
Measurement of Immunoglobulin Concentrations in the Feces of Healthy Dogs
Authors: Peters I. R. , Calvert E. L. , Hall E. J. , Day M. J.
Published: September 2004

Selective immunoglobulin A (IgA) deficiency is the most common primary immunodeficiency in humans and may be associated with chronic gastrointestinal disease. This observation has led to the suggestion that the high susceptibility of German shepherd dogs (GSD) to chronic enteropathies is related to a deficiency in mucosal IgA production. Relative deficiencies of IgA has been reported in the serum, saliva, tears, and feces of GSD both with and without alimentary disease; however, the findings of different studies are not consistent. The aim of this study was to confirm whether a relative deficiency of IgA exists in the feces of GSD. Feces were collected from healthy GSD (n= 209), Labrador retrievers (n= 96), beagles (n= 19), and miniature schnauzers (n= 32). Fecal IgA, IgM, and IgG were measured by capture enzyme-linked immunosorbent assays. Fecal IgG concentrations in the four breed groups were not significantly different. IgA concentrations were significantly greater in miniature schnauzers than in GSD (P= 0.0003) and Labradors (P= 0.0004) but not significantly different from those in beagles. IgM concentrations were significantly greater in miniature schnauzers than in GSD (P< 0.0001), Labradors (P< 0.0001), and beagles (P= 0.0098). These findings do not support the hypothesis that GSD have a relative deficiency in fecal IgA. The differences in immunoglobulin concentrations measured from a single defecation, between individuals of the same breed and between breeds, as well as the lack of an internal control molecule, make the determination of a normal reference range for all dogs impossible. Therefore, the usefulness of fecal immunoglobulin quantification for the assessment of intestinal immunoglobulin secretion in dogs is limited.
Antigen Recognition by Serum Antibodies in White-Tailed Deer (Odocoileus virginianus) Experimentally Infected withMycobacterium bovis
Authors: Waters W. R. , Palmer M. V. , Bannantine J. P. , Whipple D. L. , Greenwald R. , Esfandiari J. , Andersen P. , McNair J. , Pollock J. M. , Lyashchenko K. P.
Published: September 2004

White-tailed deer (Odocoileus virginianus) have emerged as reservoirs of bovine tuberculosis in northern America. For tuberculosis surveillance of deer, antibody-based assays are particularly attractive because deer are handled only once and immediate processing of the sample is not required. Sera collected sequentially from 25Mycobacterium bovis-infected and 7 noninfected deer were evaluated by enzyme-linked immunosorbent assay (ELISA), immunoblotting, and multiantigen print immunoassay (MAPIA) for immunoglobulin specific toM. bovisantigens. Various routes of experimentalM. bovisinfection, such as intratonsillar inoculation (n= 11), aerosol (n= 6), and exposure to infected deer (in contact,n= 8), were studied. Upon infection, specific bands of reactivity at ∼24 to 26 kDa, ∼33 kDa, ∼42 kDa, and ∼75 kDa toM. boviswhole-cell sonicate were detected by immunoblot. Lipoarabinomannan-specific immunoglobulin was detected as early as 36 days postchallenge, and responses were detected for 94% of intratonsillarly and “in-contact”-infected deer. In MAPIA, sera were tested with 12 native and recombinant antigens coated on nitrocellulose. All in-contact-infected (8 of 8) and 10 of 11 intratonsillarly infected deer produced antibody reactive with one or more of the recombinant/native antigens. Responses were boosted by injection of tuberculin for intradermal tuberculin skin testing. Additionally, three of six deer receiving a very low dose ofM. bovisvia aerosol exposure produced antibody specific to one or more recombinant proteins.M. boviswas isolated from one of three nonresponding aerosol-challenged deer. Of the 12 antigens tested, the most immunodominant protein was MPB83; however, a highly sensitive serodiagnostic test will likely require use of multiple antigens.
Effect of Photopheresis on Lymphocyte Population in Children with Newly Diagnosed Type 1 Diabetes
Authors: Ernerudh J. , Ludvigsson J. , Berlin G. , Samuelsson U.
Published: September 2004

In recent years photopheresis has been claimed to be an effective form of immunomodulation. It has also been shown to have an effect on the disease process at the onset of type 1 diabetes. In a double-blind, placebo-controlled randomized study, we analyzed if the effect of photopheresis in children with newly diagnosed diabetes is related to changes in the balance of lymhocyte populations. We also analyzed if lymphocyte subsets were related to recent infection, mild or aggressive disease manifestations, heredity, or gender. Nineteen children received active treatment with photopheresis, while 21 children received sham pheresis (placebo group). No influence of a history of previous infection, heredity, or certain clinical parameters on lymphocyte subsets was found. At the onset of type 1 diabetes, girls showed a higher proportion and a larger number of T cells (CD3
+
) and T-helper cells (CD4
+
) and a higher proportion of naïve CD4
+
CD45RA
+
cells. In the placebo group, an increase in the number of subsets with the activated phenotype in both the CD4 (CD29
+
) and the CD8 (CD11a
+
) compartments was noted during the course of the study. These changes did not occur in the photopheresis group. No relation between lymphocyte subsets and clinical outcome was found 1 year after the treatment with photopheresis. In conclusion, we found no major effect of photopheresis on lymphocyte populations in a group of children with newly diagnosed type 1 diabetes. However, in the placebo group the proportions of activated CD4 and CD8 cells increased over time. Since these changes did not occur in the actively treated group, our findings suggest that photopheresis may have some suppressive effects.
Analysis of Eight Commercial Enzyme Immunoassay Tests for Detection of Antibodies to
Mycoplasma pneumoniae
in Human Serum
Authors: Talkington Deborah F. , Shott Susan , Fallon Michael T. , Schwartz Stephanie B. , Thacker W. Lanier
Published: September 2004

Mycoplasma pneumoniae
is an important etiologic agent of primary atypical pneumonia in children and adults. The diagnosis of
M. pneumoniae
infection is commonly confirmed through serologic testing. In this study, we used paired sera from 51 patients (all with confirmed
M. pneumoniae
infection and positive complement fixation [CF] titers) to compare the results of eight enzyme immunoassays (EIAs) available commercially in the United States. We compared two single-use EIAs and six plate-type EIAs. Results from acute-phase sera ranged from only 7 (14%) positive by ImmunoWELL (GenBio) immunoglobulin M (IgM) EIA to 23 (45%) positive by Zeus IgG EIA. When both the acute-phase and convalescent-phase serum samples were examined, positive results ranged from 20 (39%) by the ImmunoWELL (GenBio) IgM assay to 45 (88%) positive by the Remel IgG-IgM EIA. In this study, the single-use EIAs by Remel and Meridian were more reliable than were the plate-type EIAs. Among the plate-type EIAs, the Zeus and DiaSorin assays (which detect antibodies to protein antigens) were more sensitive than the ImmunoWELL assay (which detects antibodies to glycolipid antigens). In general, IgG EIAs on convalescent-phase sera were more concordant with one another than were IgM EIAs with one another. Scatter plot analysis of convalescent-phase sera showed that, as the CF titer dropped, the IgM assays identified fewer positive convalescent-phase sera. In contrast, the IgG assays provided fairly consistent positive results for convalescent-phase sera with CF titers of 64 and above. Results of individual tests and overall limitations of serodiagnostics for
M. pneumoniae
infections are discussed.
Occurrence and Potential Diagnostic Applications of Serological Cross-Reactivities between
Brucella
and Other Alpha-Proteobacteria
Authors: Delpino M. Victoria , Fossati Carlos A. , Baldi Pablo C.
Published: September 2004

Agrobacterium
,
Sinorhizobium
, and
Ochrobactrum
are genera closely related to
Brucella
but, in contrast to the latter, are not pathogenic for humans and animals. We studied by an indirect enzyme-linked immunosorbent assay (ELISA) the reactivities of brucellosis sera against cytosolic (CYT) and membrane (MA) antigens from these nonpathogenic bacteria, and we evaluated the potential usefulness of these cross-reactions for the diagnosis of brucellosis in humans, sheep, cows, and dogs. Canine infection by
Brucella canis
was detected with high specificity by CYT antigen-based ELISAs (96% for
Agrobacterium
, 96% for
Sinorhizobium
, and 91% for
Ochrobactrum
), while sensitivity was variable (58% for
Agrobacterium
, 88% for
Sinorhizobium
, and 84% for
Ochrobactrum
). In addition, it was possible to diagnose canine disease shortly after exposure to the pathogen (15 days). Similar results for canine brucellosis were obtained with MA antigens. In contrast, normal sera from humans, sheep, and cattle reacted strongly with all the antigens (CYT and MA antigens from the three bacteria), producing high cutoff values and, consequently, low sensitivities. While for some host species the reactivity patterns of normal sera by Western blotting were similar to those produced with sera from infected individuals, the reactivity pattern of bovine sera against
Sinorhizobium meliloti
antigens exhibited some differential bands for the two groups of sera. These results show that crude fractions from nonpathogenic alpha-proteobacteria can be used to diagnose canine brucellosis but may need to be further separated into simpler fractions to have diagnostic usefulness in ovine, bovine, or human infection. By reducing the biosafety requirements, the use of antigens derived from these nonpathogenic bacteria would simplify the production of diagnostic kits for brucellosis, especially in settings where biosafety level-3 facilities are scarce or absent.
Analysis of Amino Acid Sequence Variations and Immunoglobulin E-Binding Epitopes of German Cockroach Tropomyosin
Authors: Jeong Kyoung Yong , Lee Jongweon , Lee In-Yong , Ree Han-Il , Hong Chein-Soo , Yong Tai-Soon
Published: September 2004

The allergenicities of tropomyosins from different organisms have been reported to vary. The cDNA encoding German cockroach tropomyosin (Bla g 7) was isolated, expressed, and characterized previously. In the present study, the amino acid sequence variations in German cockroach tropomyosin were analyzed in order to investigate its influence on allergenicity. We also undertook the identification of immunodominant peptides containing immunoglobulin E (IgE) epitopes which may facilitate the development of diagnostic and immunotherapeutic strategies based on the recombinant proteins. Two-dimensional gel electrophoresis and immunoblot analysis with mouse anti-recombinant German cockroach tropomyosin serum was performed to investigate the isoforms at the protein level. Reverse transcriptase PCR (RT-PCR) was applied to examine the sequence diversity. Eleven different variants of the deduced amino acid sequences were identified by RT-PCR. German cockroach tropomyosin has only minor sequence variations that did not seem to affect its allergenicity significantly. These results support the molecular basis underlying the cross-reactivities of arthropod tropomyosins. Recombinant fragments were also generated by PCR, and IgE-binding epitopes were assessed by enzyme-linked immunosorbent assay. Sera from seven patients revealed heterogeneous IgE-binding responses. This study demonstrates multiple IgE-binding epitope regions in a single molecule, suggesting that full-length tropomyosin should be used for the development of diagnostic and therapeutic reagents.