bluuebunny/crossref_metadata_2025 huggingface dataset:
Dose calculation formalisms and consensus dosimetry parameters for intravascular brachytherapy dosimetry: Recommendations of the AAPM Therapy Physics Committee Task Group No. 149
Authors: Chiu‐Tsao Sou‐Tung , Schaart Dennis R. , Soares Christopher G. , Nath Ravinder
Published: November 2007

Since the publication of AAPM Task Group 60 report in 1999, a considerable amount of dosimetry data for the three coronary brachytherapy systems in use in the United States has been reported. A subgroup, Task Group 149, of the AAPM working group on Special Brachytherapy Modalities (Bruce Thomadsen, Chair) was charged to develop recommendations for dose calculation formalisms and the related consensus dosimetry parameters. The recommendations of this group are presented here. For the Cordis and Novoste systems, the original TG‐43 formalism in spherical coordinates should be used along with the consensus values of the dose rate constant, geometry function, radial dose function, and anisotropy function for the single seeds. Contributions from the single seeds should be added linearly for the calculation of dose distributions from a source train. For the Guidant wire system, the modified TG‐43 formalism in cylindrical coordinates along with the recommended data for the 20 and wires should be used. Data tables for the 6, 10, 14, 18, and 22 seed trains of the Cordis system, 30, 40, and seed trains of the Novoste system, and the 20 and wires of the Guidant system are presented along with our rationale and methodology for selecting the consensus data. Briefly, all available datasets were compared with each other and the consensus dataset was either an average of available data or the one obtained from the most densely populated study; in most cases this was a Monte Carlo calculation.
The prediction of breast cancer biopsy outcomes using two CAD approaches that both emphasize an intelligible decision process
Authors: Elter M. , Schulz‐Wendtland R. , Wittenberg T.
Published: November 2007

Mammography is the most effective method for breast cancer screening available today. However, the low positive predictive value of breast biopsy resulting from mammogram interpretation leads to approximately 70% unnecessary biopsies with benign outcomes. To reduce the high number of unnecessary breast biopsies, several computer‐aided diagnosis (CAD) systems have been proposed in the last several years. These systems help physicians in their decision to perform a breast biopsy on a suspicious lesion seen in a mammogram or to perform a short term follow‐up examination instead. We present two novel CAD approaches that both emphasize an intelligible decision process to predict breast biopsy outcomes from findings. An intelligible reasoning process is an important requirement for the acceptance of CAD systems by physicians. The first approach induces a global model based on decison‐tree learning. The second approach is based on case‐based reasoning and applies an entropic similarity measure. We have evaluated the performance of both CAD approaches on two large publicly available mammography reference databases using receiver operating characteristic (ROC) analysis, bootstrap sampling, and the ANOVA statistical significance test. Both approaches outperform the diagnosis decisions of the physicians. Hence, both systems have the potential to reduce the number of unnecessary breast biopsies in clinical practice. A comparison of the performance of the proposed decision tree and CBR approaches with a state of the art approach based on artificial neural networks (ANN) shows that the CBR approach performs slightly better than the ANN approach, which in turn results in slightly better performance than the decision‐tree approach. The differences are statistically significant ( value ). On 2100 masses extracted from the DDSM database, the CRB approach for example resulted in an area under the ROC curve of , the decision‐tree approach in , and the ANN approach in .
Hybrid photoacoustic fluorescence molecular tomography using finite‐element‐based inversion
Authors: Razansky Daniel , Ntziachristos Vasilis
Published: November 2007

Improvements in fluorescence reconstruction when utilizing a hybrid photoacoustic (PAT) fluorescence molecular tomography (FMT) method to image optically heterogeneous media are studied and showcased. Quantitative optical absorption maps are retrieved using a normalized backprojection algorithm for PAT reconstruction. Consecutively, the reconstructed absorption distribution is employed into computing a diffusion‐equation‐based forward model for FMT using a finite‐element solution. The potential promise of the suggested method is experimentally verified on tissue‐mimicking fluorescent phantoms, where improvements in the quality of FMT reconstructions are observed when imaging at the presence of a large absorber.
Experimental investigation of the response of an amorphous silicon EPID to intensity modulated radiotherapy beams
Authors: Greer Peter B. , Vial Philip , Oliver Lyn , Baldock Clive
Published: November 2007

The aim of this work was to experimentally determine the difference in response of an amorphous silicon electronic portal imaging device (EPID) to the open and multileaf collimator (MLC) transmitted beam components of intensity modulated radiation therapy (IMRT) beams. EPID dose response curves were measured for open and MLC transmitted beams at central axis and with off axis distance using a shifting field technique. The EPID signal was obtained by replacing the flood‐field correction with a pixel sensitivity variation matrix correction. This signal, which includes energy‐dependent response, was then compared to ion‐chamber measurements. An EPID calibration method to remove the effect of beam energy variations on EPID response was developed for IMRT beams. This method uses the component of open and fluence to an EPID pixel calculated from the MLC delivery file and applies separate radially dependent calibration factors for each component. The calibration procedure does not correct for scatter differences between ion chamber in water measurements and EPID response; these must be accounted for separately with a kernel‐based approach or similar method. The EPID response at central axis for the open beam was found to be of the response for the beam, with the ratio increasing to 1.39 at off axis. The EPID response to radiation did not change with off‐axis distance. Filtering the beam with copper plates to reduce the beam energy difference between open and beams was investigated; however, these were not effective at reducing EPID response differences. The change in EPID response for uniform sliding window IMRT beams with dose components from 0.3% to 69% was predicted to within 2.3% using the separate EPID response calibration factors for each dose component. A clinical IMRT image calibrated with this method differed by nearly 30% in high regions from an image calibrated with an open beam calibration factor only. Accounting for the difference in EPID response to open and radiation should improve IMRT dosimetry with EPIDs.
A new method for quantitative analysis of mammographic density
Authors: Glide‐Hurst Carri K. , Duric Neb , Littrup Peter
Published: November 2007

Women with mammographic percent density have a three‐fold increased risk of developing breast cancer, potentially making them screening candidates for breast MRI scanning. The purpose of this work is to introduce a new method to quantify mammographic percent density (MPD), and to compare the results with the current standard of care for breast density assessment. Craniocaudal (CC) and mediolateral oblique (MLO) mammograms for 104 patients were digitized and analyzed using an interactive computer‐assisted segmentation routine implemented for two purposes: (1) to segment the breast area from background and radiographic markers, and (2) to segment dense from fatty portions of the breast. Our technique was evaluated by comparing the results to qualitative estimates determined by a certified breast radiologist using the BI‐RADS Categorical Assessment (1 (fatty) to 4 (dense) scale). Statistically significant correlations (two‐tailed, ) were observed between calculated MPD and BI‐RADS for both CC (Spearman ) and MLO views (Spearman ). For the CC view, statistically significant differences were revealed between the mean MPD for each BI‐RADS category except between fatty (BI‐RADS 1) and scattered (BI‐RADS 2). Finally, for the MLO views, statistically significant differences in the mean MPD between all BI‐RADS categories were observed. Comparing the CC and MLO views revealed a strong positive correlation (Pearson ) in calculated MPD. In addition, an evaluation of the reproducibility of our segmentation demonstrated the average standard deviation of MPD for a subsample of eight patients, measured five times, was 1.9% (range: 0.03%–9.9%). Eliminating one misassignment reduced the average standard deviation to 0.75% (range: 0.03%–3.16%). Further analysis of of the patient sample revealed strong agreement (ICC=0.80–0.85) in the reliability of MPD estimates for both mammographic views. Overall, these results demonstrate the feasibility of utilizing our approach for quantitative breast density segmentation, which may be useful for detecting small changes in MPD introduced through chemoprevention, diet, or other interventions.
Design and evaluation of a variable aperture collimator for conformal radiotherapy of small animals using a microCT scanner
Authors: Graves Edward E. , Zhou Hu , Chatterjee Raja , Keall Paul J. , Gambhir Sanjiv Sam , Contag Christopher H. , Boyer Arthur L.
Published: November 2007

Treatment of small animals with radiation has in general been limited to planar fields shaped with lead blocks, complicating spatial localization of dose and treatment of deep‐seated targets. In order to advance laboratory radiotherapy toward what is accomplished in the clinic, we have constructed a variable aperture collimator for use in shaping the beam of microCT scanner. This unit can image small animal subjects at high resolution, and is capable of delivering therapeutic doses in reasonable exposure times. The proposed collimator consists of two stages, each containing six trapezoidal brass blocks that move along a frame in a manner similar to a camera iris producing a hexagonal aperture of variable size. The two stages are offset by 30° and adjusted for the divergence of the x‐ray beam so as to produce a dodecagonal profile at isocenter. Slotted rotating driving plates are used to apply force to pins in the collimator blocks and effect collimator motion. This device has been investigated through both simulation and measurement. The collimator aperture size varied from as the driving plate angle increased from 0 to 41°. The torque required to adjust the collimator varied from , increasing with increasing driving plate angle. The transmission profiles produced by the scanner at isocenter exhibited a penumbra of approximately 10% of the collimator aperture width. Misalignment between the collimator assembly and the x‐ray source could be identified on the transmission images and corrected by adjustment of the collimator location. This variable aperture collimator technology is therefore a feasible and flexible solution for adjustable shaping of radiation beams for use in small animal radiotherapy as well as other applications in which beam shaping is desired.
Realtime light dosimetry software tools for interstitial photodynamic therapy of the human prostate
Authors: Johansson Ann , Axelsson Johan , Andersson‐Engels Stefan , Swartling Johannes
Published: November 2007

Photodynamic therapy (PDT) for the treatment of prostate cancer has been demonstrated to be a safe treatment option capable of inducing tissue destruction and decreasing prostate specific antigen (PSA) levels. However, prostate‐PDT results in large intra‐ and interpatient variations in treatment response, possibly due to biological variations in tissue composition and short‐term response to the therapeutic irradiation. Within our group, an instrument for interstitial PDT on prostate tissue has been developed that combines therapeutic light delivery and monitoring of light transmission via numerous bare‐ended optical fibers. Here, we present algorithms that utilize data on the light distribution within the target tissue to provide realtime treatment feedback based on a light dose threshold model for PDT. This realtime dosimetry module is implemented to individualize the light dose and compensate for any treatment‐induced variations in light attenuation. More specifically, based on the light transmission signals between treatment fibers, spatially resolved spectroscopy is utilized to assess the effective attenuation coefficient of the tissue. These data constitute input to a block‐Cimmino optimization algorithm, employed to calculate individual fiber irradiation times provided the requirement to deliver a predetermined light dose to the target tissue while sparing surrounding sensitive organs. By repeatedly monitoring the light transmission signals during the entire treatment session, optical properties and individual fiber irradiation times are updated in realtime. The functionality of the algorithms is tested on diffuse light distribution data simulated by means of the finite element method (FEM). The feasibility of utilizing spatially resolved spectroscopy within heterogeneous media such as the prostate gland is discussed. Furthermore, we demonstrate the ability of the block‐Cimmino algorithm to discriminate between target tissue and organs at risk (OAR). Finally, the realtime dosimetry module is evaluated for treatment scenarios displaying spatially and temporally varying light attenuation levels within the target tissue. We conclude that the realtime dosimetry module makes it possible to deliver a certain light dose to the target tissue despite spatial and temporal variations of the target tissue optical properties at the therapeutic wavelength.
Automated volume analysis of head and neck lesions on CT scans using 3D level set segmentation
Authors: Street Ethan , Hadjiiski Lubomir , Sahiner Berkman , Gujar Sachin , Ibrahim Mohannad , Mukherji Suresh K. , Chan Heang‐Ping
Published: November 2007

The authors have developed a semiautomatic system for segmentation of a diverse set of lesions in head and neck CT scans. The system takes as input an approximate bounding box, and uses a multistage level set to perform the final segmentation. A data set consisting of 69 lesions marked on 33 scans from 23 patients was used to evaluate the performance of the system. The contours from automatic segmentation were compared to both 2D and 3D gold standard contours manually drawn by three experienced radiologists. Three performance metric measures were used for the comparison. In addition, a radiologist provided quality ratings on a 1 to 10 scale for all of the automatic segmentations. For this pilot study, the authors observed that the differences between the automatic and gold standard contours were larger than the interobserver differences. However, the system performed comparably to the radiologists, achieving an average area intersection ratio of compared to an average of between two radiologists. The average absolute area error was compared to , and the average 2D distance was 1.38 mm compared to 0.84 mm between the radiologists. In addition, the quality rating data showed that, despite the very lax assumptions made on the lesion characteristics in designing the system, the automatic contours approximated many of the lesions very well.
Development of a fully automatic scheme for detection of masses in whole breast ultrasound images
Authors: Ikedo Yuji , Fukuoka Daisuke , Hara Takeshi , Fujita Hiroshi , Takada Etsuo , Endo Tokiko , Morita Takako
Published: November 2007

Ultrasonography has been used for breast cancer screening in Japan. Screening using a conventional hand‐held probe is operator dependent and thus it is possible that some areas of the breast may not be scanned. To overcome such problems, a mechanical whole breast ultrasound (US) scanner has been proposed and developed for screening purposes. However, another issue is that radiologists might tire while interpreting all images in a large‐volume screening; this increases the likelihood that masses may remain undetected. Therefore, the aim of this study is to develop a fully automatic scheme for the detection of masses in whole breast US images in order to assist the interpretations of radiologists and potentially improve the screening accuracy. The authors database comprised 109 whole breast US images, which include 36 masses (16 malignant masses, 5 fibroadenomas, and 15 cysts). A whole breast US image with 84 slice images (interval between two slice images: 2 mm) was obtained by the ASU‐1004 US scanner (ALOKA Co., Ltd., Japan). The feature based on the edge directions in each slice and a method for subtracting between the slice images were used for the detection of masses in the authors proposed scheme. The Canny edge detector was applied to detect edges in US images; these edges were classified as near‐vertical edges or near‐horizontal edges using a morphological method. The positions of mass candidates were located using the near‐vertical edges as a cue. Then, the located positions were segmented by the watershed algorithm and mass candidate regions were detected using the segmented regions and the low‐density regions extracted by the slice subtraction method. For the removal of false positives (FPs), rule‐based schemes and a quadratic discriminant analysis were applied for the distribution between masses and FPs. As a result, the sensitivity of the authors scheme for the detection of masses was (29/36) with 3.8 FPs per whole breast image. The authors scheme for a computer‐aided detection may be useful in improving the screening performance and efficiency.
High sensitivity radiochromic film dosimetry using an optical common‐mode rejection and a reflective‐mode flatbed color scanner
Authors: Ohuchi Hiroko
Published: November 2007

A novel method that can greatly improve the dosimetric sensitivity limit of a radiochromic film (RCF) through use of a set of color components, e.g., red and green, outputs from a RGB color scanner has been developed. RCFs are known to have microscopic and macroscopic nonuniformities, which come from the thickness variations in the film's active radiochromic layer and coating. These variations in the response make the optical signal‐to‐noise ratio lower, resulting in lower film sensitivity. To mitigate the effects of RCF nonuniform response, an optical common‐mode rejection (CMR) was developed. The CMR compensates nonuniform response by creating a ratio of the two signals where the factors common to both numerator and denominator cancel out. The CMR scheme was applied to the mathematical operation of creating a ratio using two components, red and green outputs from a scanner. The two light component lights are neighboring wavebands about 100 nm apart and suffer a common fate, with the exception of wavelength‐dependent events, having passed together along common attenuation paths. Two types of dose‐response curves as a function of delivered dose ranging from 3.7 mGy to 8.1 Gy for 100 kV x‐ray beams were obtained with the optical CMR scheme and the conventional analysis method using red component, respectively. In the range of 3.7 mGy to 81 mGy, the optical densities obtained with the optical CMR showed a good consistency among eight measured samples and an improved consistency with a linear fit within 1 standard deviation of each measured optical densities, while those with the conventional analysis exhibited a large discrepancy among eight samples and did not show a consistency with a linear fit.
A boundary element approach for image‐guided near‐infrared absorption and scatter estimation
Authors: Srinivasan Subhadra , Pogue Brian W. , Carpenter Colin , Yalavarthy Phaneendra K. , Paulsen Keith
Published: November 2007

Multimodality NIR spectroscopy systems offer the possibility of region‐based vascular and molecular characterization of tissue in vivo. However, computationally efficient 3D image reconstruction algorithms specific to these image‐guided systems currently do not exist. Image reconstruction is often based on finite‐element methods (FEMs), which require volume discretization. Here, a boundary element method (BEM) is presented using only surface discretization to recover the optical properties in an image‐guided setting. The reconstruction of optical properties using BEM was evaluated in a domain containing a 30 mm inclusion embedded in two layer media with different noise levels and initial estimates. For noise in measurements, and background starting values for reconstruction, the optical properties were recovered to within a mean error of . When compared with FEM for this case, BEM showed a improvement in computational time. BEM was also applied to experimental data collected from a gelatin phantom with a 25 mm inclusion and could recover the true absorption to within of expected values using less time for computation compared with FEM. When applied to a patient‐specific breast mesh generated using MRI, with a 2 cm ductal carcinoma, BEM showed successful recovery of optical properties with less than error in absorption and error in scattering, using measurements with noise. With simpler and faster meshing schemes required for surface grids as compared with volume grids, BEM offers a powerful and potentially more feasible alternative for high‐resolution 3D image‐guided NIR spectroscopy.
Clinical 3 T Magnetic Resonance
Authors: Nelson Michael T.
Published: November 2007

Clinical 3 T Magnetic Resonance Runge V. M. Nitz W. R. Schmeets S. H. Schoenberg S. O. Thieme Medical Publishers, Inc., New York, 2007. 264 pp. $49.95/EUR 39.95. ISBN: 9781588904034/9783131411013.
Menin Controls Growth of Pancreatic ß-Cells in Pregnant Mice and Promotes Gestational Diabetes Mellitus
Authors: Karnik Satyajit K. , Chen Hainan , McLean Graeme W. , Heit Jeremy J. , Gu Xueying , Zhang Andrew Y. , Fontaine Magali , Yen Michael H. , Kim Seung K.
Published: November 2007

During pregnancy, maternal pancreatic islets grow to match dynamic physiological demands, but the mechanisms regulating adaptive islet growth in this setting are poorly understood. Here we show that menin, a protein previously characterized as an endocrine tumor suppressor and transcriptional regulator, controls islet growth in pregnant mice. Pregnancy stimulated proliferation of maternal pancreatic islet β-cells that was accompanied by reduced islet levels of menin and its targets. Transgenic expression of menin in maternal β-cells prevented islet expansion and led to hyperglycemia and impaired glucose tolerance, hallmark features of gestational diabetes. Prolactin, a hormonal regulator of pregnancy, repressed islet menin levels and stimulated β-cell proliferation. These results expand our understanding of mechanisms underlying diabetes pathogenesis and reveal potential targets for therapy in diabetes.
Nanoscale Friction Varied by Isotopic Shifting of Surface Vibrational Frequencies
Authors: Cannara Rachel J. , Brukman Matthew J. , Cimatu Katherine , Sumant Anirudha V. , Baldelli Steven , Carpick Robert W.
Published: November 2007

Friction converts kinetic energy at sliding interfaces into lattice vibrations, but the detailed mechanisms of this process remain unresolved. Atomic force microscopy measurements reveal that changing the mass of the terminating atoms on a surface, and thus their vibrational frequencies, affects nanoscale friction substantially. We compared hydrogen- and deuterium-terminated single-crystal diamond and silicon surfaces, and in all cases the hydrogenated surface exhibited higher friction. This result implies that the lower natural frequency of chemisorbed deuterium reduces the rate at which the tip's kinetic energy is dissipated. This discovery is consistent with a model describing energy transfer to adsorbates from a moving surface.
Molecular and Genomic Data Identify the Closest Living Relative of Primates
Authors: Janečka Jan E. , Miller Webb , Pringle Thomas H. , Wiens Frank , Zitzmann Annette , Helgen Kristofer M. , Springer Mark S. , Murphy William J.
Published: November 2007

A full understanding of primate morphological and genomic evolution requires the identification of their closest living relative. In order to resolve the ancestral relationships among primates and their closest relatives, we searched multispecies genome alignments for phylogenetically informative rare genomic changes within the superordinal group Euarchonta, which includes the orders Primates, Dermoptera (colugos), and Scandentia (treeshrews). We also constructed phylogenetic trees from 14 kilobases of nuclear genes for representatives from most major primate lineages, both extant colugos, and multiple treeshrews, including the pentail treeshrew,
Ptilocercus lowii
, the only living member of the family Ptilocercidae. A relaxed molecular clock analysis including
Ptilocercus
suggests that treeshrews arose approximately 63 million years ago. Our data show that colugos are the closest living relatives of primates and indicate that their divergence occurred in the Cretaceous.
Happy 300th Birthday, Linnaeus
Authors: Bohannon John
Published: November 2007

In addition to inventing modern taxonomy, Carl Linnaeus published works on the origin, preparation, serving, and health effects of food. To celebrate the 300th anniversary of Linnaeus's birth, the Gonzo Scientist spends 3 days in Sweden sampling recreations of 18th century meals, from peasant food to a royal banquet.
Comparison of Two Commercially Available Gamma Interferon Blood Tests for Immunodiagnosis of Tuberculosis
Authors: Domínguez Jose , Ruiz-Manzano Juan , De Souza-Galvão Malú , Latorre Irene , Milà Celia , Blanco Silvia , Jiménez M. Ángeles , Prat Cristina , Lacoma Alicia , Altet Neus , Ausina Vicente
Published: November 2007

We evaluated the T-SPOT.TB and Quantiferon-TB Gold
In tube
(QFN-G-IT) tests for diagnosing
Mycobacterium tuberculosis
infection. T-SPOT.TB was more sensitive than QFN-G-IT in diagnosing both active and latent infection. Both gamma interferon tests were unaffected by prior
Mycobacterium bovis
BCG vaccination. Among children who were not BCG vaccinated but had a positive tuberculin skin test, QFN-G-IT was negative in 53.3% of cases, and T-SPOT.TB was negative in 50% of cases.
“Mid-G” Region Sequences of the Glycoprotein Gene of Austrian Infectious Hematopoietic Necrosis Virus Isolates Form Two Lineages within European Isolates and Are Distinct from American and Asian Lineages
Authors: Kolodziejek Jolanta , Schachner Oskar , Dürrwald Ralf , Latif Muna , Nowotny Norbert
Published: November 2007

Infectious hematopoietic necrosis virus (IHNV) is one of the most important pathogens of salmonid fish. In this study a comprehensive phylogenetic analysis of the genetic evolution and variety of Austrian IHNV strains, as well as selected strains ensuring worldwide coverage, is presented. The phylogenetic investigation is based on sequences comprising the “mid-G” region of the G gene, and it includes all currently available IHNV sequences of the G gene with a length of at least 615 bp. Austrian IHNVs are located—together with other European IHNV isolates—in two clusters of genogroup M (M-Eur1 and M-Eur2) and are clearly separated from American and Asian lineages. The genetic clustering, however, could not be linked to certain clinical symptoms or significant differences in the mortality rates.
Emergence of Clonal Complex 17
Enterococcus faecium
in The Netherlands
Authors: Top Janetta , Willems Rob , van der Velden Saskia , Asbroek Miranda , Bonten Marc
Published: November 2007

The global emergence of vancomycin-resistant
Enterococcus faecium
has been characterized as the clonal spread of clonal complex 17 (CC17)
E. faecium
. CC17 was defined upon multilocus sequence typing and is characterized by resistance to quinolones and ampicillin and the presence of the enterococcal surface protein (Esp) in the majority of isolates. The recently noticed increased incidence of vancomycin-susceptible CC17
E. faecium
infections in our hospital initiated a nationwide study to determine ecological changes among enterococcal infections. The data and strain collections were obtained from 26 (38%) and 9 (14%) of 66 microbiology laboratories in The Netherlands.
E. faecium
and
E. faecalis
were distinguished by multiplex PCR; all
E. faecium
isolates were genotyped by multiple-locus variable-number tandem-repeat analysis (MLVA), and the presence of
esp
was identified by PCR. Average numbers of ampicillin-resistant enterococcal isolates from normally sterile body sites per hospital increased from 5 ± 1 in 1994 to 25 ± 21 in 2005. Among all enterococcal bloodstream infections, the proportions of ampicillin-resistant
E. faecium
(AREF) increased from 4% in 1994 to 20% in 2005 (
P
< 0.001). All
E. faecalis
isolates were susceptible to ampicillin, whereas 78% of the
E. faecium
isolates were resistant (49% of these contained
esp
). Genotyping revealed that 86% of AREF isolates belonged to CC17, including four dominant MLVA types found in ≥3 hospitals, accounting for 64% of the AREF isolates. Infections caused by CC17
E. faecium
has increased nationwide, especially in university hospitals due to the clonal spread of four MLVA types, and seems associated with acquisition of the
esp
gene.
Novel
Brucella
Strain (BO1) Associated with a Prosthetic Breast Implant Infection
Authors: De Barun K. , Stauffer Larry , Koylass Mark S. , Sharp Susan E. , Gee Jay E. , Helsel Leta O. , Steigerwalt Arnold G. , Vega Robert , Clark Thomas A. , Daneshvar Maryam I. , Wilkins Patricia P. , Whatmore Adrian M.
Published: November 2007

We report the microbiological, biochemical, and molecular characterization of an unusual
Brucella
strain (BO1) isolated from a breast implant wound in a 71-year-old woman with clinical symptoms consistent with brucellosis. Initial phenotypic analysis, including biochemical and antimicrobial susceptibility testing, cellular fatty acid analysis, and molecular analysis based on DNA-DNA reassociation and the presence of multiple copies of IS
711
element suggested that the isolate was a
Brucella
-like organism, but species determination using microbiological algorithms was unsuccessful. Furthermore, molecular data based on 16S rRNA gene sequencing and multilocus sequence analysis demonstrated that BO1 was an unusual
Brucella
strain and not closely related to any currently described
Brucella
species. However, comparison with equivalent sequences in
Ochrobactrum
spp. confirms that the isolate is much more closely related to
Brucella
than to
Ochrobactrum
spp., and thus the isolate likely represents an atypical and novel strain within the genus
Brucella
.
Cervical Human Papillomavirus (HPV) Infection in South African Women: Implications for HPV Screening and Vaccine Strategies
Authors: Allan Bruce , Marais Dianne J. , Hoffman Margaret , Shapiro Samuel , Williamson Anna-Lise
Published: November 2007

The prevalence of cervical human papillomavirus (HPV) in South African women (
n
= 1,073) increased from 20.4% (173/848) in women with normal cytology to 41.7% (48/115) in women with atypical squamous cells of undetermined significance, 70.2% (40/57) in women with low-grade squamous intraepithelial lesions, and 83% (44/53) in women with high-grade squamous intraepithelial lesions (HSILs). HPV types 16 and 35 were the dominant types in women with HSILs but not in women in the other categories.
Clonal Focusing of Epitope-Specific CD8+T Lymphocytes in Rhesus Monkeys following Vaccination and Simian-Human Immunodeficiency Virus Challenge
Authors: Sen Pritha , Charini William A. , Subbramanian Ramu A. , Manuel Edwin R. , Kuroda Marcelo J. , Autissier Patrick A. , Letvin Norman L.
Published: November 2007

To afford the greatest possible immune protection, candidate human immunodeficiency virus (HIV) vaccines must generate diverse and long-lasting CD8+T lymphocyte responses. In the present study, we evaluate T-cell receptor Vβ (variable region beta) gene usage and a CDR3 (complementarity-determining region 3) sequence to assess the clonality of epitope-specific CD8+T lymphocytes generated in rhesus monkeys following vaccination and simian-human immunodeficiency virus (SHIV) challenge. We found that vaccine-elicited epitope-specific CD8+T lymphocytes have a clonal diversity comparable to those cells generated in response to SHIV infection. Moreover, we show that the clonal diversity of vaccine-elicited CD8+T-lymphocyte responses is dictated by the epitope sequence and is not affected by the mode of antigen delivery to the immune system. Clonal CD8+T-lymphocyte populations persisted following boosting with different vectors, and these clonal cell populations could be detected for as long as 4 years after SHIV challenge. Finally, we show that the breadth of these epitope-specific T lymphocytes transiently focuses in response to intense SHIV replication. These observations demonstrate the importance of the initial immune response to SHIV, induced by vaccination or generated during primary infection, in determining the clonal diversity of cell-mediated immune responses and highlight the focusing of this clonal diversity in the setting of high viral loads. Circumventing this restricted CD8+T-lymphocyte clonal diversity may present a significant challenge in the development of an effective HIV vaccine strategy.
The 3′ Untranslated Region of Sindbis Virus Represses Deadenylation of Viral Transcripts in Mosquito and Mammalian Cells
Authors: Garneau Nicole L. , Sokoloski Kevin J. , Opyrchal Mateusz , Neff C. Preston , Wilusz Carol J. , Wilusz Jeffrey
Published: November 2007

The positive-sense transcripts of Sindbis virus (SINV) resemble cellular mRNAs in that they possess a 5′ cap and a 3′ poly(A) tail. It is likely, therefore, that SINV RNAs must successfully overcome the cytoplasmic mRNA decay machinery of the cell in order to establish an efficient, productive infection. In this study, we have taken advantage of a temperature-sensitive polymerase to shut off viral transcription, and we demonstrate that SINV RNAs are subject to decay during a viral infection in both C6/36 (
Aedes albopictus
) and baby hamster kidney cells. Interestingly, in contrast to most cellular mRNAs, the decay of SINV RNAs was not initiated by poly(A) tail shortening in either cell line except when most of the 3′ untranslated region (UTR) was deleted from the virus. This block in deadenylation of viral transcripts was recapitulated in vitro using C6/36 mosquito cell cytoplasmic extracts. Two distinct regions of the 319-base SINV 3′ UTR, the repeat sequence elements and a U-rich domain, were shown to be responsible for mediating the repression of deadenylation of viral mRNAs. Through competition studies performed in parallel with UV cross-linking and functional assays, mosquito cell factors—including a 38-kDa protein—were implicated in the repression of deadenylation mediated by the SINV 3′ UTR. This same 38-kDa protein was also implicated in mediating the repression of deadenylation by the 3′ UTR of another alphavirus, Venezuelan equine encephalitis virus. In summary, these data provide clear evidence that SINV transcripts do indeed interface with the cellular mRNA decay machinery during an infection and that the virus has evolved a way to avoid the major deadenylation-dependent pathway of mRNA decay.
Murine Gammaherpesvirus 68 Genes both Induce and Suppress Lymphoproliferative Disease
Authors: Tarakanova Vera L. , Kreisel Friederike , White Douglas W. , Virgin Herbert W.
Published: November 2007

Gammaherpesvirus infection is associated with an increased incidence of lymphoproliferative disease in immunocompromised hosts. Murine gammaherpesvirus 68 (γHV68) infection of BALB β
2
-microglobulin-deficient (BALB β
2
m
−/−
) mice provides an animal model for analysis of the mechanisms responsible for the induction of a lymphoproliferative disease, atypical lymphoid hyperplasia (ALH), that is pathologically similar to posttransplant lymphoproliferative disease associated with Epstein-Barr virus infection. Here we report that the γHV68
v-cyclin
and
v-bcl-2
genes are required for the efficient induction of γHV68-associated ALH in BALB β
2
m
−/−
mice, while the
v-GPCR
gene is dispensable for ALH induction. In contrast to these findings, deletion of the viral
M1
gene enhanced ALH. Thus, γHV68 genes can either inhibit or enhance the induction of lymphoproliferative disease in immunocompromised mice.
Antibody Profiling by Proteome Microarray Reveals the Immunogenicity of the Attenuated Smallpox Vaccine Modified Vaccinia Virus Ankara Is Comparable to That of Dryvax
Authors: Davies D. Huw , Wyatt Linda S. , Newman Frances K. , Earl Patricia L. , Chun Sookhee , Hernandez Jenny E. , Molina Douglas M. , Hirst Siddiqua , Moss Bernard , Frey Sharon E. , Felgner Philip L.
Published: November 2007

Modified vaccinia virus Ankara (MVA) is a highly attenuated vaccinia virus that is under consideration as an alternative to the conventional smallpox vaccine Dryvax. MVA was attenuated by extensive passage of vaccinia virus Ankara in chicken embryo fibroblasts. Several immunomodulatory genes and genes that influence host range are deleted or mutated, and replication is aborted in the late stage of infection in most nonavian cells. The effect of these mutations on immunogenicity is not well understood. Since the structural genes appear to be intact in MVA, it is hypothesized that critical targets for antibody neutralization have been retained. To test this, we probed microarrays of the Western Reserve (WR) proteome with sera from humans and macaques after MVA and Dryvax vaccination. As most protein sequences of MVA are 97 to 99% identical to those of other vaccinia virus strains, extensive binding cross-reactivity is expected, except for those deleted or truncated. Despite different hosts and immunization regimens, the MVA and Dryvax antibody profiles were broadly similar, with antibodies against membrane and core proteins being the best conserved. The responses to nonstructural proteins were less well conserved, although these are not expected to influence virus neutralization. The broadest antibody response was obtained for hyperimmune rabbits with WR, which is pathogenic in rabbits. These data indicate that, despite the mutations and deletions in MVA, its overall immunogenicity is broadly comparable to that of Dryvax, particularly at the level of antibodies to membrane proteins. The work supports other information suggesting that MVA may be a useful alternative to Dryvax.
Varicella-Zoster Virus Glycoprotein M Homolog Is Glycosylated, Is Expressed on the Viral Envelope, and Functions in Virus Cell-to-Cell Spread
Authors: Yamagishi Yoshiaki , Sadaoka Tomohiko , Yoshii Hironori , Somboonthum Pranee , Imazawa Takayoshi , Nagaike Kazuhiro , Ozono Keiichi , Yamanishi Koichi , Mori Yasuko
Published: November 2007

Although envelope glycoprotein M (gM) is highly conserved among herpesviruses, the varicella-zoster virus (VZV) gM homolog has never been investigated. Here we characterized the VZV gM homolog and analyzed its function in VZV-infected cells. The VZV gM homolog was expressed on virions as a glycoprotein modified with a complex N-linked oligosaccharide and localized mainly to the Golgi apparatus and the
trans
-Golgi network in infected cells. To analyze its function, a gM deletion mutant was generated using the bacterial artificial chromosome system in
Escherichia coli
, and the virus was reconstituted in MRC-5 cells. VZV is highly cell associated, and infection proceeds mostly by cell-to-cell spread. Compared with wild-type VZV, the gM deletion mutant showed a 90% reduction in plaque size and 50% of the cell-to-cell spread in MRC-5 cells. The analysis of infected cells by electron microscopy revealed numerous aberrant vacuoles containing electron-dense materials in cells infected with the deletion mutant virus but not in those infected with wild-type virus. However, enveloped immature particles termed L particles were found at the same level on the surfaces of cells infected with either type of virus, indicating that envelopment without a capsid might not be impaired. These results showed that VZV gM is important for efficient cell-to-cell virus spread in cell culture, although it is not essential for virus growth.
Herpes Simplex Virus Type 1 Preferentially Targets Human Colon Carcinoma: Role of Extracellular Matrix
Authors: Kolodkin-Gal Dror , Zamir Gideon , Edden Yair , Pikarsky Eli , Pikarsky Alon , Haim Hillel , Haviv Yosef S. , Panet Amos
Published: November 2007

Viral therapy of cancer (viral oncolysis) is dependent on selective destruction of the tumor tissue compared with healthy tissues. Several factors, including receptor expression, extracellular components, and intracellular mechanisms, may influence viral oncolysis. In the present work, we studied the potential oncolytic activity of herpes simplex virus type 1 (HSV-1), using an organ culture system derived from colon carcinoma and healthy colon tissues of mouse and human origin. HSV-1 infected normal colons ex vivo at a very low efficiency, in contrast to high-efficiency infection of colon carcinoma tissue. In contrast, adenoviral and lentiviral vectors infected both tissues equally well. To investigate the mechanisms underlying the preferential affinity of HSV-1 for the carcinoma tissue, intracellular and extracellular factors were investigated. Two extracellular components, collagen and mucin molecules, were found to restrict HSV-1 infectivity in the healthy colon. The mucin layer of the healthy colon binds to HSV-1 and thereby blocks viral interaction with the epithelial cells of the tissue. In contrast, colon carcinomas express small amounts of collagen and mucin molecules and are thus permissive to HSV-1 infection. In agreement with the ex vivo system, HSV-1 injected into a mouse colon carcinoma in vivo significantly reduced the volume of the tumor. In conclusion, we describe a novel mechanism of viral selectivity for malignant tissues that is based on variance of the extracellular matrix between tumor and healthy tissues. These insights may facilitate new approaches to the application of HSV-1 as an oncolytic virus.
Isolation and Characterization of Broadly Neutralizing Human Monoclonal Antibodies to the E1 Glycoprotein of Hepatitis C Virus
Authors: Meunier Jean-Christophe , Russell Rodney S. , Goossens Vera , Priem Sofie , Walter Hugo , Depla Erik , Union Ann , Faulk Kristina N. , Bukh Jens , Emerson Suzanne U. , Purcell Robert H.
Published: November 2007

The relative importance of humoral and cellular immunity in the prevention or clearance of hepatitis C virus (HCV) infection is poorly understood. However, there is considerable evidence that neutralizing antibodies are involved in disease control. Here we describe the detailed analysis of human monoclonal antibodies (MAbs) directed against HCV glycoprotein E1, which may have the potential to control HCV infection. We have identified two MAbs that can strongly neutralize HCV-pseudotyped particles (HCVpp) bearing the envelope glycoproteins of genotypes 1a, 1b, 4a, 5a, and 6a and less strongly neutralize HCVpp bearing the envelope glycoproteins of genotype 2a. Genotype 3a was not neutralized. The epitopes for both MAbs were mapped to the region encompassing amino acids 313 to 327. In addition, robust neutralization was also observed against cell culture-adapted viruses of genotypes 1a and 2a. Results from this study suggest that these MAbs may have the potential to prevent HCV infection.
Paramyxovirus-Induced Shutoff of Host and Viral Protein Synthesis: Role of the P and V Proteins in Limiting PKR Activation
Authors: Gainey Maria D. , Dillon Patrick J. , Clark Kimberly M. , Manuse Mary J. , Parks Griffith D.
Published: November 2007

The paramyxovirus simian virus 5 (SV5) establishes highly productive persistent infections of epithelial cells without inducing a global inhibition of translation. Here we show that an SV5 mutant (the P/V-CPI
−
mutant) with substitutions in the P subunit of the viral polymerase and the accessory V protein also establishes highly productive infections like wild-type (WT) SV5 but that cells infected with the P/V-CPI
−
mutant show an overall shutdown of both host and viral translation at late times postinfection. Reduced host and viral protein synthesis with the P/V-CPI
−
virus was not due to lower levels of mRNA or caspase-dependent apoptosis and correlated with phosphorylation of the translation initiation factor eIF-2α. WT SV5 was a poor activator of the eIF-2α kinase protein kinase R (PKR). By contrast, the P/V-CPI
−
mutant induced PKR phosphorylation, which correlated with the time course of translation inhibition but was independent of interferon signaling. In HeLa cells that expressed the PKR inhibitor influenza A virus NS1 or reovirus sigma3, the rate of host protein synthesis at late times after infection with the P/V-CPI
−
mutant was restored to ∼50% that of control HeLa cells. By contrast, the rates of P/V-CPI
−
viral protein synthesis in HeLa cells expressing NS1 or sigma3 were dramatically enhanced, between 5- and 20-fold, while levels of viral mRNA were increased only slightly (NS1-expressing cells) or remained constant (sigma3-expressing cells). Similar results were found using HeLa cells where PKR levels were reduced due to knockdown by small interfering RNA. Expression of either the WT P or the WT V protein from the genome of the P/V-CPI
−
mutant resulted in lower levels of PKR activation and rates of host and viral protein synthesis that closely matched those seen with WT SV5. Despite higher rates of translation, cells infected with the V- or P-complemented virus accumulated viral mRNAs to lower levels than that seen with the parental P/V-CPI
−
mutant. We present a model in which the paramyxovirus P/V gene products limit induction of PKR by limiting the synthesis of aberrant viral mRNAs and double-stranded RNA and thus prevent the shutdown of translation by a mechanism that differs from that of other PKR inhibitors such as NS1 and sigma3.
AN IMPLICATION OF "GRAVITY AS THE WEAKEST FORCE"
Authors: MEDVED A. J. M.
Published: November 2007

The negative specific heat of a radiating black hole is indicative of a cataclysmic endpoint to the evaporation process. In this letter, we suggest a simple mechanism for circumventing such a dramatic outcome. The basis for our argument is a conjecture that was recently proposed by Arkani-Hamed and collaborators. To put it another way, we use their notion of "Gravity as the Weakest Force" as a means of inhibiting the process of black hole evaporation.
COULOMB SCATTERING OF THE DIRAC FERMIONS ON DE SITTER EXPANDING UNIVERSE
Authors: CRUCEAN COSMIN
Published: November 2007

The lowest order contribution of the amplitude of the Dirac–Coulomb scattering in de Sitter spacetime is calculated assuming that the initial and final states of the Dirac field are described by exact solutions of the free Dirac equation on de Sitter spacetime with a given momentum and helicity. One studies the difficulties that arises when one passes from the amplitude to cross section.
CHARGED ROTATING BLACK HOLES IN DILATON GRAVITY
Authors: SHEYKHI A. , RIAZI N.
Published: November 2007

We consider charged black holes with curved horizons, in five-dimensional dilaton gravity in the presence of Liouville-type potential for the dilaton field. We show how, by solving a pair of coupled differential equations, infinitesimally small angular momentum can be added to these static solutions to obtain charged rotating dilaton black hole solutions. In the absence of dilaton field, the nonrotating version of the solution reduces to the five-dimensional Reissner–Nordström black hole, and the rotating version reproduces the five-dimensional Kerr–Newman modification thereof for small rotation parameter. We also compute the angular momentum and the angular velocity of these rotating black holes which appear at the first order.