bluuebunny/crossref_metadata_2025_split huggingface dataset:
SonoKnife: Feasibility of a line‐focused ultrasound device for thermal ablation therapy
Authors: Chen Duo , Xia Rongmin , Chen Xin , Shafirstein Gal , Corry Peter M. , Griffin Robert J. , Penagaricano Jose A. , Tulunay‐Ugur Ozlem E. , Moros Eduardo G. 
Published: June 2011

Purpose:To evaluate the feasibility of line‐focused ultrasound for thermal ablation of superficially located tumors.Methods:A SonoKnife is a cylindrical‐section ultrasound transducer designed to radiate from its concave surface. This geometry generates a line‐focus or acoustic edge. The motivation for this approach was the noninvasive thermal ablation of advanced head and neck tumors and positive neck nodes in reasonable treatment times. Line‐focusing may offer advantages over the common point‐focusing of spherically curved radiators such as faster coverage of a target volume by scanning of the acoustic edge. In this paper, The authors report studies using numerical models and phantom andex vivo experiments using a SonoKnife prototype.Results: Acoustic edges were generated by cylindrical‐section single‐element ultrasound transducers numerically, and by the prototype experimentally. Numerically, simulations were performed to characterize the acoustic edge for basic design parameters: transducer dimensions, line‐focus depth, frequency, and coupling thickness. The dimensions of the acoustic edge as a function of these parameters were determined. In addition, a step‐scanning simulation produced a large thermal lesion in a reasonable treatment time. Experimentally, pressure distributions measured in degassed water agreed well with acoustic simulations, and sonication experiments in gel phantoms andex vivo porcine liver samples produced lesions similar to those predicted with acoustic and thermal models.Conclusions: Results support the feasibility of noninvasive thermal ablation with a SonoKnife.
Characterization of imaging performance in differential phase contrast CT compared with the conventional CT—Noise power spectrum NPS(k)
Authors: Tang Xiangyang , Yang Yi , Tang Shaojie 
Published: June 2011

Purpose:The differential phase contrast CT is emerging as a new technology to improve the contrast sensitivity of the conventional CT. Via system analysis, modeling, and computer simulation, the authors study the noise power spectrum (NPS)—an imaging performance indicator—of the differential phase contrast CT and compare it with that of the conventional CT.Methods:The differential phase contrast CT is implemented with x‐ray tube and gratings. The x‐ray propagation and data acquisition are modeled and simulated with Fourier analysis and Fresnel analysis. To avoid any interference caused by scatter and beam hardening, a monochromatic x‐ray source (30 keV) is assumed, which irradiates the object to be imaged by 360° so that no weighting scheme is needed. A 20‐fold up‐sampling is assumed to simulate x‐ray beam's propagation through the gratingsG1 and G2 with periods 8 and 4 μm, respectively, while the intergrating distance is 193.6 mm (1/16 of the Tabolt distance). The dimension of the detector cell for data acquisition ranges from 32 × 32 to 128 × 128 μm2, while the field of view in data acquisition is 40.96 × 40.96 mm2. A uniform water phantom with a diameter 37.68 mm is employed to study the NPS, with its complex refraction coefficient n = 1 − δ + iβ = 1 − 2.5604 × 10−7 + i1.2353 × 10−10. The x‐ray flux ranges from 106 to 108 photon/cm2·projection and observes the Poisson distribution, which is consistent with that of micro‐CT in preclinical applications. The image matrix of reconstructed water phantom is 1280 × 1280, and a total of 180 regions at 128 × 128 matrix are used for NPS calculation via 2D Fourier Transform in which adequate zero padding is applied to avoid aliasing.Results:The preliminary data show that the differential phase contrast CT manifests its NPS with a 1/|k| trait, while the distribution of the conventional CTs NPS observes |k|. This accounts for the significant difference in their noise granularity and the differential phase contrast CTs substantial advantage in noise over the conventional CT, particularly, in the situations where the detector cell size for data acquisition is smaller than 100 μm.Conclusions:The differential phase contrast CT detects the projection of refractive coefficient's derivative and uses the Hilbert filter for image reconstruction, which leads to the radical difference in its NPS and the advantage in noise in comparison to that of the conventional CT.
Overestimations in zero frequency DQE of x‐ray imaging converters assessed by Monte Carlo techniques based on the study of energy impartation events
Authors: Liaparinos P. F. , Kandarakis I. S. 
Published: June 2011

Purpose:The performance of various x‐ray converters, employed in medical imaging systems, has been widely examined by several methodologies (experimental, analytical, and Monte Carlo techniques). The x‐ray converters most frequently employed in energy integrating digital radiology detectors are the Gd2O2S:Tb granular phosphor, the CsI:Tl structured phosphor, and the a‐Se photoconductor. The imaging characteristics of an x‐ray converter are affected by its x‐ray detection properties. However, various definitions of x‐ray detection have been used in the literature, leading to different results for the quantum detection efficiency (QDE) for the same type of x‐ray converter. For this reason, there is a need for accurate determination of the x‐ray detection and, in particular, its relation to detector response.Methods:The present article reports on the performance of the three aforementioned x‐ray converters in terms of the QDE and the x‐ray statistical factor and examines the effect of the x‐ray detection, directly related to converter output signal, on the zero‐frequency DQE. For the purposes of this study, Monte Carlo simulation was used to model the x‐ray interactions within the x‐ray converter. Simulations were carried out in the energy range from 10 keV up to 80 keV and considering two layers of different coating weights (50 and 100 mg/cm2). The prediction and comparison of zero‐frequency DQE were based on two different approaches for x‐ray detection, i.e., (a) fraction of interacting photons and (b) fraction of photons leading to energy deposition. In addition, the effect of energy deposition through Compton scattering events on the DQE values was estimated.Results:Our results showed discrepancies between Monte Carlo techniques (based on energy deposition events) and analytical calculations (based on x‐ray attenuation) on QDE. Discrepancies were found to range up to 10% for Gd2O2S:Tb (100 mg/cm2), 7.7% for CsI:Tl (50 mg/cm2), and 8.2% for a‐Se (50 mg/cm2). Discrepancies were analyzed by examining the scattering effects (elastic and inelastic) within the converters and led to further analysis of scattering events on as well. Significant overestimations were found for both factors (QDE and ) on the zero‐frequency DQE.Conclusions:Considering that the highest overestimation was found in the thin layer (50 mg/cm2), Monte Carlo evaluation showed that the overestimation (%) between DQE values (based on either x‐ray interacting events or energy impartation events) was more significant at 20 keV for CsI:Tl (approximately 2.1%), at 40 keV for Gd2O2S:Tb (approximately 8.1%), and finally at 60 and 80 keV for a‐Se converter (approximately 4.8 and 8.2%, respectively). Finally, the overestimation due to the effect of Compton scattering on DQE was found more significant for the a‐Se converter and especially above 40 keV reaching approximately the value of 8.9% at 80 keV.
Quantitative analysis of beam delivery parameters and treatment process time for proton beam therapy
Authors: Suzuki Kazumichi , Gillin Michael T. , Sahoo Narayan , Zhu X. Ronald , Lee Andrew K. , Lippy Denise 
Published: June 2011

Purpose:To evaluate patient census, equipment clinical availability, maximum daily treatment capacity, use factor for major beam delivery parameters, and treatment process time for actual treatments delivered by proton therapy systems.Methods:The authors have been recording all beam delivery parameters, including delivered dose, energy, range, spread‐out Bragg peak widths, gantry angles, and couch angles for every treatment field in an electronic medical record system. We analyzed delivery system downtimes that had been recorded for every equipment failure and associated incidents. These data were used to evaluate the use factor of beam delivery parameters, the size of the patient census, and the equipment clinical availability of the facility. The duration of each treatment session from patient walk‐in and to patient walk‐out of the treatment room was measured for 82 patients with cancers at various sites.Results:The yearly average equipment clinical availability in the last 3 yrs (June 2007–August 2010) was 97%, which exceeded the target of 95%. Approximately 2200 patients had been treated as of August 2010. The major disease sites were genitourinary (49%), thoracic (25%), central nervous system (22%), and gastrointestinal (2%). Beams have been delivered in approximately 8300 treatment fields. The use factor for six beam delivery parameters was also evaluated. Analysis of the treatment process times indicated that approximately 80% of this time was spent for patient and equipment setup. The other 20% was spent waiting for beam delivery and beam on. The total treatment process time can be expressed by a quadratic polynomial of the number of fields per session. The maximum daily treatment capacity of our facility using the current treatment processes was estimated to be 133 ± 35 patients.Conclusions:This analysis shows that the facility has operated at a high performance level and has treated a large number of patients with a variety of diseases. The use factor of beam delivery parameters varies by disease site. Further improvements in efficiency may be realized in the equipment‐ and patient‐related processes of treatment.
Development of an Automated, High-Throughput Bactericidal Assay That Measures Cellular Respiration as a Survival Readout for Neisseria meningitidis
Authors: Mak Puiying A. , Santos George F. , Masterman Kelly-Anne , Janes Jeff , Wacknov Bill , Vienken Kay , Giuliani Marzia , Herman Ann E. , Cooke Michael , Mbow M. Lamine , Donnelly John 
Published: June 2011

ABSTRACTComplement-mediated bactericidal activity has long been regarded as the serological correlate of protective immunity againstNeisseria meningitidis. This was affirmed in 2005 at a WHO-sponsored meningococcal serology standardization workshop. The assay currently employed by most laboratories involves determining surviving bacterial colony counts on agar as a readout which is labor-intensive, time-consuming, and not amendable to rapid data analysis for clinical trials. Consequently, there is an acute need to develop a sensitive, high-throughput bactericidal assay to enable a rapid and robust assessment of the effectiveness of vaccine candidates. To this end, we have developed an automated, kinetic assay based on the fluorescent respiration product of resazurin which reduces assay volume, shortens assay time, and facilitates automation of data analysis. We demonstrate proof of concept for applicability of this high-throughput system with multiple meningococcal strains and utilizing different lots of human complement. The assay is robust and highly reproducible. Titers obtained by the fluorescence readout method are strongly correlated with the data obtained using the conventional, agar plate-based assay. These results demonstrate that the detection of bacteria that have survived the bactericidal reaction by measuring metabolic activity using a fluorescent dye as an alternative readout is a promising approach for the development of a high-throughput bactericidal assay.
Allele-Specific Real-Time PCR System for Detection of Subpopulations of Genotype 1a and 1b Hepatitis C NS5B Y448H Mutant Viruses in Clinical Samples
Authors: Bae Andrew S. , Ku Karin S. , Miller Michael D. , Mo Hongmei , Svarovskaia Evguenia S. 
Published: June 2011

ABSTRACT

The Y448H mutation in NS5B has been selected by GS-9190 as well as several benzothiadiazine hepatitis C virus (HCV) polymerase inhibitors
in vitro
and
in vivo
. However, the level and the evolution kinetics of this resistance mutation prior to and during treatment are poorly understood. In this study, we developed an allele-specific real-time PCR (AS-PCR) assay capable of detecting Y448H when it was present at a level down to 0.5% within an HCV population of genotype 1a or 1b. No Y448H mutation was detected above the assay cutoff of 0.5% in genotype 1b-infected Con-1 replicons prior to
in vitro
treatment. However, the proportion of replicons with the Y448H mutation rapidly increased in a dose-dependent manner upon treatment with GS-9190. After 3 days of treatment, 1.2%, 6.8%, and >50% of the replicon population expressed Y448H with the use of GS-9190 at 1, 10, and 20 times its 50% effective concentration, respectively. In addition, plasma from 65 treatment-naïve HCV-infected patients (42 and 23 with genotype 1a and 1b, respectively) was tested for the presence of Y448H by AS-PCR and population sequencing. As expected, all patient samples were wild type at NS5B Y448 by population sequencing. AS-PCR results were obtained for 62/65 samples tested, with low levels of Y448H ranging from 0.5% to 3.0% detected in 5/62 (8%) treatment-naïve patient samples. These findings suggest the need for combination therapy with HCV-specific inhibitors to avoid viral rebound of preexisting mutant HCV.
Legionella micdadei, a New Cause of Prosthetic Joint Infection
Authors: Fernández-Cruz Ana , Marín Mercedes , Castelo Laura , Usubillaga Rafael , Martín-Rabadán Pablo , Bouza Emilio ,   the GAIO (Group for the Assessment of Osteoarticular Infections) Study Group
Published: June 2011

ABSTRACT

Extrapulmonary infections caused by
Legionella
spp. other than
Legionella pneumophila
are rare. We report what is, to our knowledge, the first description of a prosthetic joint infection due to
Legionella
spp. Systematic testing of samples with suspected prosthetic infection by molecular biology techniques was essential.
Legionella micdadei
should be added to the list of microorganisms causing prosthetic joint infection.
Molecular Characterization of a Catalase-Negative Staphylococcus aureus subsp.
aureus
Strain Collected from a Patient with Mitral Valve Endocarditis and Pericarditis Revealed a Novel Nonsense Mutation in the
katA
Gene
Authors: To Kelvin K. W. , Cheng Vincent C. C. , Chan Jasper F. W. , Wong Amy C. Y. , Chau Sandy , Tsang Flora H. F. , Curreem Shirly O. T. , Lau Susanna K. P. , Yuen Kwok-Yung , Woo Patrick C. Y. 
Published: June 2011

ABSTRACT

We report a case of endocarditis and pericarditis caused by catalase-negative
Staphylococcus aureus
. Molecular characterization revealed a novel nonsense mutation in the
katA
gene, leading to a loss of 238 amino acids (47% of the wild-type catalase protein), including the heme-binding site, NADPH-binding region, and Tyr-337, essential for catalysis.
Analysis of Intrahost Variation in Venezuelan Equine Encephalitis Virus Reveals Repeated Deletions in the 6-Kilodalton Protein Gene
Authors: Forrester N. L. , Guerbois M. , Adams A. P. , Liang X. , Weaver S. C. 
Published: June 2011

ABSTRACT

RNA viruses exist as a spectrum of mutants that is generated and maintained during replication within the host. Consensus sequencing overlooks minority genotypes present in the viral sample that may impact the population's phenotype. In-depth sequencing of an original field isolate of subtype IE Venezuelan equine encephalitis virus (VEEV) demonstrated the presence of multiple deletions within the 6,000-molecular-weight (6K) protein gene. Using
in vitro
and
in vivo
experiments, similar deletions were generated in an additional VEEV strain originating from an infectious cDNA clone. Time course experiments demonstrated that the deletions are produced during acute infection although not until 24 h postinfection. Molecular clones containing some of these deletions were generated, and although the larger deletions appear to be noninfectious, viruses with the smaller deletions were viable and formed small plaques. Serial passages provided no evidence that these deletion mutants function as defective interfering particles. Furthermore, since wild-type infections generally occur at a low multiplicity of infection, it is unlikely that these deletions are propagated in natural transmission cycles. However, they could affect pathogenesis at later stages of infection. Because they are ubiquitously generated both
in vivo
and
in vitro
, further investigation is warranted to understand the generation of these deletions and their significance for disease.
M94 Is Essential for the Secondary Envelopment of Murine Cytomegalovirus
Authors: Maninger Silke , Bosse Jens Bernhard , Lemnitzer Frederic , Pogoda Madlen , Mohr Christian A. , von Einem Jens , Walther Paul , Koszinowski Ulrich H. , Ruzsics Zsolt 
Published: June 2011

ABSTRACT
The gene M94 of murine cytomegalovirus (MCMV) as well as its homologues UL16 in alphaherpesviruses is involved in viral morphogenesis. For a better understanding of its role in the viral life cycle, a library of random M94 mutants was generated by modified transposon-based linker scanning mutagenesis. A comprehensive set of M94 mutants was reinserted into the MCMV genome and tested for their capacity to complement the M94 null mutant. Thereby, 34 loss-of-function mutants of M94 were identified, which were tested in a second screen for their capacity to inhibit virus replication. This analysis identified two N-terminal insertion mutants of M94 with a dominant negative effect. We compared phenotypes induced by the conditional expression of these dominant negative M94 alleles with the null phenotype of the M94 deletion. The viral gene expression cascade and the nuclear morphogenesis steps were not affected in either setting. In both cases, however, secondary envelopment did not proceed in the absence of functional M94, and capsids subsequently accumulated in the center of the cytoplasmic assembly complex. In addition, deletion of M94 resulted in a block of cell-to-cell spread. Moreover, the dominant negative mutant of M94 demonstrated a defect in interacting with M99, the UL11 homologue of MCMV.
Comparative Evolution of GII.3 and GII.4 Norovirus over a 31-Year Period
Authors: Boon Denali , Mahar Jackie E. , Abente Eugenio J. , Kirkwood Carl D. , Purcell Robert H. , Kapikian Albert Z. , Green Kim Y. , Bok Karin 
Published: June 2011

ABSTRACT

Noroviruses are the most common cause of epidemic gastroenteritis. Genotype II.3 is one of the most frequently detected noroviruses associated with sporadic infections. We studied the evolution of the major capsid gene from seven archival GII.3 noroviruses collected during a cross-sectional study at the Children's Hospital in Washington, DC, from 1975 through 1991, together with capsid sequence from 56 strains available in GenBank. Evolutionary analysis concluded that GII.3 viruses evolved at a rate of 4.16 × 10
−3
nucleotide substitutions/site/year (strict clock), which is similar to that described for the more prevalent GII.4 noroviruses. The analysis of the amino acid changes over the 31-year period found that GII.3 viruses evolve at a relatively steady state, maintaining 4% distance, and have a tendency to revert back to previously used residues while preserving the same carbohydrate binding profile. In contrast, GII.4 viruses demonstrate increasing rates of distance over time because of the continued integration of new amino acids and changing HBGA binding patterns. In GII.3 strains, seven sites acting under positive selection were predicted to be surface-exposed residues in the P2 domain, in contrast to GII.4 positively selected sites located primarily in the shell domain. Our study suggests that GII.3 noroviruses caused disease as early as 1975 and that they evolve via a specific pattern, responding to selective pressures induced by the host rather than presenting a nucleotide evolution rate lower than that of GII.4 noroviruses, as previously proposed. Understanding the evolutionary dynamics of prevalent noroviruses is relevant to the development of effective prevention and control strategies.
Comprehensive Proteomic Analysis of Influenza Virus Polymerase Complex Reveals a Novel Association with Mitochondrial Proteins and RNA Polymerase Accessory Factors
Authors: Bradel-Tretheway Birgit G. , Mattiacio Jonelle L. , Krasnoselsky Alexei , Stevenson Catherine , Purdy David , Dewhurst Stephen , Katze Michael G. 
Published: June 2011

ABSTRACT
The trimeric RNA polymerase complex (3P, for PA-PB1-PB2) of influenza A virus (IAV) is an important viral determinant of pathogenicity and host range restriction. Specific interactions of the polymerase complex with host proteins may be determining factors in both of these characteristics and play important roles in the viral life cycle. To investigate this question, we performed a comprehensive proteomic analysis of human host proteins associated with the polymerase of the well-characterized H5N1 Vietnam/1203/04 isolate. We identified over 400 proteins by liquid chromatography-tandem mass spectrometry (LC-MS/MS), of which over 300 were found to bind to the PA subunit alone. The most intriguing and novel finding was the large number of mitochondrial proteins (∼20%) that associated with the PA subunit. These proteins mediate molecular transport across the mitochondrial membrane or regulate membrane potential and may in concert with the identified mitochondrion-associated apoptosis inducing factor (AIFM1) have roles in the induction of apoptosis upon association with PA. Additionally, we identified host factors that associated with the PA-PB1 (68 proteins) and/or the 3P complex (34 proteins) including proteins that have roles in innate antiviral signaling (e.g., ZAPS or HaxI) or are cellular RNA polymerase accessory factors (e.g., polymerase I transcript release factor [PTRF] or Supt5H). IAV strain-specific host factor binding to the polymerase was not observed in our analysis. Overall, this study has shed light into the complex contributions of the IAV polymerase to host cell pathogenicity and allows for direct investigations into the biological significance of these newly described interactions.
Adenovirus E1A Directly Targets the E2F/DP-1 Complex
Authors: Pelka Peter , Miller Matthew S. , Cecchini Matthew , Yousef Ahmed F. , Bowdish Dawn M. , Dick Fred , Whyte Peter , Mymryk Joe S. 
Published: June 2011

ABSTRACT
Deregulation of the cell cycle is of paramount importance during adenovirus infection. Adenovirus normally infects quiescent cells and must initiate the cell cycle in order to propagate itself. The pRb family of proteins controls entry into the cell cycle by interacting with and repressing transcriptional activation by the E2F transcription factors. The viral E1A proteins indirectly activate E2F-dependent transcription and cell cycle entry, in part, by interacting with pRb and family members to free the E2Fs. We report here that an E1A 13S isoform can unexpectedly activate E2F-responsive gene expression independently of binding to the pRb family of proteins. We demonstrate that E1A binds to E2F/DP-1 complexes through a direct interaction with DP-1. E1A appears to utilize this binding to recruit itself to E2F-regulated promoters, and this allows the E1A 13S protein, but not the E1A 12S protein, to activate transcription independently of interaction with pRb. Importantly, expression of E1A 13S, but not E1A 12S, led to significant enhancement of E2F4 occupancy of E2F sites of two E2F-regulated promoters. These observations identify a novel mechanism by which adenovirus deregulates the cell cycle and suggest that E1A 13S may selectively activate a subset of E2F-regulated cellular genes during infection.