bluuebunny/crossref_metadata_2025 huggingface dataset:
Ignition Delay and Combustion Characteristics of Gaseous Fuel Jets
Authors: Nguyen Dung Ngoc , Ishida Hiroaki , Shioji Masahiro
Published: January 2010

Gaseous fuels, such as hydrogen and natural gas, are utilized in internal combustion engines for spark-ignition operation. To improve thermal efficiency and to ensure control at good heat-release rates, combustion systems with direct-injection and spontaneous-ignition operation may be preferable. The main objective of this research was to provide fundamental data for the ignition and combustion of hydrogen, natural gas, and methane. Experiments were conducted in a constant-volume combustion vessel to investigate the effects of ambient temperature on ignition delay and combustion characteristics for various injector and ambient conditions. Experimental results showed that all gaseous fuels exhibited similar ignition-delay trends: ignition delay (τ) increased as ambient temperature (Ti) decreased. Among these fuels, hydrogen jets exhibited much shorter τ than natural gas and methane jets at the same Ti and could be ignited at a lower temperature, Ti=780 K. A shorter ignition delay of hydrogen may be attained by controlling the mixture formation by lowering the injection pressure (pj), enlarging the nozzle-hole diameter (dN), increasing the ambient pressure (pi), and increasing the oxygen mole fraction (rO2). In contrast, the methane jet exhibited the longest τ over the whole range of Ti and suffered from misfiring at a higher Ti of 910 K. For natural gas, ignition delay was observed to be shorter than that for methane, owing to a small amount of butane with good ignitability. More specifically, the ignition delay of natural gas differed slightly when dN and pj varied but changed drastically when pi and rO2 decreased. Based on these data, the feasibility of gaseous fuels for compression-ignition engines is discussed from the viewpoint of mixture formation and chemical reaction.
The use of PET images for radiotherapy treatment planning: An error analysis using radiobiological endpoints
Authors: Perrin R. , Evans P. M. , Webb S. , Partridge M.
Published: January 2010

Purpose:

There is significant current interest in the use of biological image guidance in radiotherapy planning. In lung‐cancer treatment, tumor motion due to respiration is known to be a limitation. This is particularly true in PET, where image data are collected over a number of minutes. An in‐house‐developed 4D PET acquisition mode is described and an analysis of the effects of acquisition parameters on the reconstructed image quality is presented. The potential impact of the resulting biological image quality on radiotherapy planning is then quantified in terms of tumor control probability (TCP).

Methods:

Data were acquired using a human torso phantom comprised of a hot‐filled spheroidal “tumor” ( in diameter) suspended in an air‐filled “lung” cylinder and surrounded by a warm ‐filled background. Two different sphere‐to‐background (S/B) ratios were used. The tumor was connected to a 3‐axis computer‐controlled motion stage and could be moved during PET data acquisition. Images were acquired with a range of count statistics, motion blurring, and CT attenuation correction (CTAC) misalignment. Four simple models were proposed for the assignment of clonogenic cell density according to the voxel value. The impact of image artifacts was then assessed by calculating the TCP, which is the probability that no clonogenic tumor cell remains after a given dose of radiation. TCP was calculated for a uniform dose distribution in the tumor.

Results:

Reduced count statistics and misaligned CTAC images had the most detrimental impact on the image fidelity. It was found that in both cases the images became less intense, demonstrated by smaller number of voxels at the maximum values. The maximum TCP difference between images with the least and most noise was 3.4%, and with weakest and strongest CT misalignment artifacts, it was 3.2% . Motion blurring only contributed weakly to the TCP imprecision at 1.7% between best‐ and worst‐case images. However, the model‐calculated TCP showed increasing differences from the ground truth as the complexity of the model increased [maximum difference of (model 3)], which could be attributed to the partial volume effect.

Conclusions:

Based on the results of this study, it is believed that simple techniques of biologically guided radiotherapy planning for lung cancer should be feasible at intermediate contrast levels (tumor‐to‐background ratio of) with the clinically achievable image quality.
Impact of anatomical interventions on the localization of post‐prostatectomy cancer patients
Authors: Diot Quentin , Olsen Christine , Kavanagh Brian , Raben David , Miften Moyed
Published: January 2010

Purpose:

Anatomical deformations of prostate‐bed, rectum, and bladder can compromise the targeting accuracy in post‐prostatectomy cancer patients. In this work, the impact of anatomical interventions on the localization data from post‐prostatectomy patients who received image‐guided IMRT was analyzed.

Methods:

Patients were localized daily with online kilovoltage cone‐beam computed tomography (kV‐CBCT). The target and the organs at risk (OARs) positional and volumetric changes were evaluated and couch shifts were applied. For patients with large target or OAR volumetric changes, quantified by either a rectal or bladder wall displacement of on the CBCT sagittal images compared to the planning CT, repeated localization CBCT scans were performed following an interventional procedure. The procedure involves insertion of a catheter to deflate the rectum, evacuation of stools, and/or adjustment of bladder filling. The required shifts were then evaluated, and the IMRT treatment was subsequently delivered after proper patient positioning. The pre‐ and post‐intervention shifts were compared in the lateral [left‐right (LR)], longitudinal [superior‐inferior (SI)], and vertical [anterior‐posterior (AP)] directions. The percentage of shifts larger than 5 mm in all directions was also compared. Clinical target volume to planning target volume (CTV‐to‐PTV) expansion margins were estimated based on the pre‐ and post‐intervention localization data.

Results:

Intervention was performed on all patients treated between October 2008 and March 2009. The number of interventions ranged from 2 to 12 with a median number of 5, resulting in a total of 96 pairs of pre‐ and post‐intervention shifts. The mean value and standard deviation of the shifts from pre‐ versus post‐intervention data were LR, vs ; SI, vs ; and AP, vs . The mean 3D shift distance was vs . The percentage of pre‐intervention shifts larger than 5 mm were 7%, 7%, and 45% in the LR, SI, and AP directions, respectively, compared to 8%, 4%, and 21% for post‐intervention. Localization data from pre‐ and post‐intervention procedures suggest that treatments that do not include intervention to correct for rectum/bladder anatomical variations require an additional 3.3 mm CTV‐to‐PTV margin.

Conclusions:

Anatomical interventions reduced the localization errors arising from large volume and shape changes in the rectum and/or bladder compared to treatments without interventions.
Dosimetric validation of a commercial Monte Carlo based IMRT planning system
Authors: Grofsmid Dennis , Dirkx Maarten , Marijnissen Hans , Woudstra Evert , Heijmen Ben
Published: January 2010

Purpose:

Recently a commercial Monte Carlo based IMRT planning system (Monaco version 1.0.0) was released. In this study the dosimetric accuracy of this new planning system was validated.

Methods:

Absolute dose profiles, depth dose curves, and output factors calculated by Monaco were compared with measurements in a water phantom. Different static on‐axis and off‐axis fields were tested at various source‐skin distances for 6, 10, and 18 MV photon beams. Four clinical IMRT plans were evaluated in a water phantom using a linear diode detector array and another six IMRT plans for different tumor sites in solid water using a 2D detector array. In order to evaluate the accuracy of the dose engine near tissue inhomogeneities absolute dose distributions were measured with Gafchromic EBT film in an inhomogeneous slab phantom. For an end‐to‐end test a four‐field IMRT plan was applied to an anthropomorphic lung phantom with a simulated tumor peripherally located in the right lung. Gafchromic EBT film, placed in and around the tumor area, was used to evaluate the dose distribution.

Results:

Generally, the measured and the calculated dose distributions agreed within 2% dose difference or 2 mm distance‐to‐agreement. But mainly at interfaces with bone, some larger dose differences could be observed.

Conclusions:

Based on the results of this study, the authors concluded that the dosimetric accuracy of Monaco is adequate for clinical introduction.
Accurate MTF measurement in digital radiography using noise response
Authors: Kuhls‐Gilcrist Andrew , Jain Amit , Bednarek Daniel R. , Hoffmann Kenneth R. , Rudin Stephen
Published: January 2010

Purpose:

The authors describe a new technique to determine the system presampled modulation transfer function (MTF) in digital radiography using only the detector noise response.

Methods:

A cascaded‐linear systems analysis was used to develop an exact relationship between the two‐dimensional noise power spectrum (NPS) and the presampled MTF for a generalized detector system. This relationship was then utilized to determine the two‐dimensional presampled MTF. For simplicity, aliasing of the correlated noise component of the NPS was assumed to be negligible. Accuracy of this method was investigated using simulated images from a simple detector model in which the “true” MTF was known exactly. Measurements were also performed on three detector technologies (an x‐ray image intensifier, an indirect flat panel detector, and a solid state x‐ray image intensifier), and the results were compared using the standard edge‐response method. Flat‐field and edge images were acquired and analyzed according to guidelines set forth by the International Electrotechnical Commission, using the RQA 5 spectrum.

Results:

The presampled MTF determined using the noise‐response method for the simulated detector system was in close agreement with the true MTF with an averaged percent difference of 0.3% and a maximum difference of 1.1% observed at the Nyquist frequency. The edge‐response method of the simulated detector system also showed very good agreement at lower spatial frequencies (less than ) with an averaged percent difference of 1.6% but showed significant discrepancies at higher spatial frequencies (greater than ) with an averaged percent difference of 17%. Discrepancies were in part a result of noise in the edge image and phasing errors. For all three detector systems, the MTFs obtained using the two methods were found to be in good agreement at spatial frequencies less than with an averaged percent difference of 3.4%. Above , differences increased to an average of 20%. Deviations of the experimental results largely followed the trend seen in the simulation results, suggesting that differences between the two methods could be explained as resulting from the inherent inaccuracies of the edge‐response measurement technique used in this study. Aliasing of the correlated noise component was shown to have a minimal effect on the measured MTF for the three detectors studied. Systems with significant aliasing of the correlated noise component (e.g., based detectors) would likely require a more sophisticated fitting scheme to provide accurate results.

Conclusions:

Results indicate that the noise‐response method, a simple technique, can be used to accurately measure the MTF of digital x‐ray detectors, while alleviating the problems and inaccuracies associated with use of precision test objects, such as a slit or an edge.
Near optimal energy selective x‐ray imaging system performance with simple detectors
Authors: Alvarez Robert E.
Published: January 2010

Purpose:

This article describes a method to achieve near optimal performance with low energy resolution detectors. Tapiovaara and Wagner [Phys. Med. Biol. 30, 519–529 (1985)] showed that an energy selective x‐ray system using a broad spectrum source can produce images with a larger signal to noise ratio (SNR) than conventional systems using energy integrating or photon counting detectors. They showed that there is an upper limit to the SNR and that it can be achieved by measuring full spectrum information and then using an optimal energy dependent weighting.

Methods:

A performance measure is derived by applying statistical detection theory to an abstract vector space of the line integrals of the basis set coefficients of the two function approximation to the x‐ray attenuation coefficient. The approach produces optimal results that utilize all the available energy dependent data. The method can be used with any energy selective detector and is applied not only to detectors using pulse height analysis (PHA) but also to a detector that simultaneously measures the total photon number and integrated energy, as discussed by Roessl et al. [Med. Phys. 34, 959–966 (2007)]. A generalization of this detector that improves the performance is introduced. A method is described to compute images with the optimal SNR using projections in a “whitened” vector space transformed so the noise is uncorrelated and has unit variance in both coordinates. Material canceled images with optimal SNR can also be computed by projections in this space.

Results:

The performance measure is validated by showing that it provides the Tapiovaara–Wagner optimal results for a detector with full energy information and also a conventional detector. The performance with different types of detectors is compared to the ideal SNR as a function of x‐ray tube voltage and subject thickness. A detector that combines two bin PHA with a simultaneous measurement of integrated photon energy provides near ideal performance across a wide range of operating conditions.

Conclusions:

Low energy resolution detectors can be used in energy selective x‐ray imaging systems to produce images with near optimal performance.
Slow gantry rotation acquisition technique for on‐board four‐dimensional digital tomosynthesis
Authors: Maurer Jacqueline , Pan Tinsu , Yin Fang‐Fang
Published: January 2010

Purpose:

Four‐dimensional cone‐beam computed tomography (4D CBCT) has been investigated for motion imaging in the radiotherapy treatment room. The drawbacks of 4D CBCT are long scan times and high imaging doses. The aims of this study were to develop and investigate a slow gantry rotation acquisition protocol for four‐dimensional digital tomosynthesis (4D DTS) as a faster, lower dose alternative to 4D CBCT.

Methods:

This technique was implemented using an On‐Board Imager® kV imaging system (Varian Medical Systems, Palo Alto, CA) mounted on the gantry of a linear accelerator. The general procedure for 4D DTS imaging using slow gantry rotation acquisition consists of the following steps: (1) acquire projections over a limited gantry rotation angle in a single motion with constant frame rate and gantry rotation speed; (2) generate a respiratory signal and temporally match projection images with appropriate points from the respiratory signal; (3) use the respiratory signal to assign phases to each of the projection images; (4) sort projection images into phase bins; and (5) reconstruct phase images. Phantom studies were conducted to validate theoretically derived relationships between acquisition and respiratory parameters. Optimization of acquisition parameters was then conducted by simulating lung scans using patient data. Lung tumors with approximate volumes ranging from 0.12 to were studied.

Results:

A protocol for slow gantry rotation 4D DTS was presented. Equations were derived to express relationships between acquisition parameters (frame rate, phase window, and angular intervals between projections), respiratory cycle durations, and resulting acquisition times and numbers of projections. The phantom studies validated the relationships, and the patient studies resulted in determinations of appropriate acquisition parameters. The phase window must be set according to clinical goals. For 10% phase windows, we found that appropriate frame rates ranging from 2 to 5 frames/s, gantry rotation speeds ranging from 0.44 to 1.03°/s, and aiming for an approximate maximum angular interval of 3.4° between projections in phase bins were appropriate for dose, scan time, and tumor visibility optimization. Adequate tumor visibility was achieved for coronal 4D DTS images of all three lung tumors with acquisition times ranging from 0.45 to 2.12 min. vs 1.84 to 4.24 min for 4D CBCT. 4D DTS imaging doses ranged from 0.12 to 0.72 times the dose of a standard CBCT scan vs 0.48 to 1.44 times the dose of a standard CBCT scan for 4D CBCT.

Conclusions:

A slow gantry rotation acquisition technique for 4D DTS was developed and investigated. Study results indicated that 4D DTS is a feasible technique for imaging lung tumor motion in the treatment room and requires shorter acquisition times and less imaging dose than 4D CBCT for larger tumors that do not require large scan angles for sagittal views and for situations where only coronal views are needed to meet clinical needs.
Dosimetric accuracy of a deterministic radiation transport based brachytherapy treatment planning system. Part I: Single sources and bounded homogeneous geometries
Authors: Zourari K. , Pantelis E. , Moutsatsos A. , Petrokokkinos L. , Karaiskos P. , Sakelliou L. , Georgiou E. , Papagiannis P.
Published: January 2010

Purpose:

The aim of this work is to validate a deterministic radiation transport based treatment planning system (TPS) for single brachytherapy source dosimetry in homogeneous water geometries.

Methods:

TPS results were obtained using the deterministic radiation transport option of aBRACHYVISION v. 8.8 system for three characteristic source designs (VS2000, GMPlus HDR, and GMPlus PDR) with each source either centered in a 15 cm radius spherical water phantom, or positioned at varying distance away from the phantom center. Corresponding MC simulations were performed using the MCNPX code v.2.5.0 and source geometry models prepared using information provided by the manufacturers.

Results:

Comparison in terms of the AAPM TG‐43 dosimetric formalism quantities, as well as dose rate distributions per unit air kerma strength with a spatial resolution of 0.1 cm, yielded close agreement between TPS and MC results for the sources centered in the phantom. Besides some regions close to the source longitudinal axes where discrepancies could be characterized as systematic, overall agreement for all three sources studied is comparable to the statistical (type A) uncertainty of MC simulations (1% at the majority of points in the geometry increasing to 2%–3% at points lying both away from the source center and close to the source longitudinal axis). A corresponding good agreement was also found between TPS and MC results for the sources positioned away from the phantom center.

Conclusions:

Results of this work attest the capability of the TPS to accurately account for the scatter conditions regardless of the size or shape of a given geometry of dosimetric interest, and the position of a source within it. This is important since, as shown in the literature and summarized also in this work, these factors could introduce a significant dosimetric effect that is currently ignored in clinical treatment planning. It is concluded that the implementation of the deterministic radiation transport option of theBRACHYVISION v. 8.8 system for brachytherapy dosimetry in homogeneous water geometries yields results of comparable accuracy to the golden standard of Monte Carlo simulation, in clinically viable calculation times.
Influence of photon energy spectra from brachytherapy sources on Monte Carlo simulations of kerma and dose rates in water and air
Authors: Rivard Mark J. , Granero Domingo , Perez‐Calatayud Jose , Ballester Facundo
Published: January 2010

Purpose:

For a given radionuclide, there are several photon spectrum choices available to dosimetry investigators for simulating the radiation emissions from brachytherapy sources. This study examines the dosimetric influence of selecting the spectra for, , and on the final estimations of kerma and dose.

Methods:

For, , and , the authors considered from two to five published spectra. Spherical sources approximating common brachytherapy sources were assessed. Kerma and dose results from GEANT4, MCNP5, and PENELOPE‐2008 were compared for water and air. The dosimetric influence of , , and spectral choice was determined.

Results:

For the spectra considered, there were no statistically significant differences between kerma or dose results based on Monte Carlo code choice when using the same spectrum. Water‐kerma differences of about 2%, 2%, and 0.7% were observed due to spectrum choice for, , and , respectively (independent of radial distance), when accounting for photon yield per Bq. Similar differences were observed for air‐kerma rate. However, their ratio (as used in the dose‐rate constant) did not significantly change when the various photon spectra were selected because the differences compensated each other when dividing dose rate by air‐kerma strength.

Conclusions:

Given the standardization of radionuclide data available from the National Nuclear Data Center (NNDC) and the rigorous infrastructure for performing and maintaining the data set evaluations, NNDC spectra are suggested for brachytherapy simulations in medical physics applications.
Scatter correction method for x‐ray CT using primary modulation: Phantom studies
Authors: Gao Hewei , Fahrig Rebecca , Bennett N. Robert , Sun Mingshan , Star‐Lack Josh , Zhu Lei
Published: January 2010

Purpose:

Scatter correction is a major challenge in x‐ray imaging using large area detectors. Recently, the authors proposed a promising scatter correction method for x‐ray computed tomography (CT) using primary modulation. Proof of concept was previously illustrated by Monte Carlo simulations and physical experiments on a small phantom with a simple geometry. In this work, the authors provide a quantitative evaluation of the primary modulation technique and demonstrate its performance in applications where scatter correction is more challenging.

Methods:

The authors first analyze the potential errors of the estimated scatter in the primary modulation method. On two tabletop CT systems, the method is investigated using three phantoms: A Catphan©600 phantom, an anthropomorphic chest phantom, and the Catphan©600 phantom with two annuli. Two different primary modulators are also designed to show the impact of the modulator parameters on the scatter correction efficiency. The first is an aluminum modulator with a weak modulation and a low modulation frequency, and the second is a copper modulator with a strong modulation and a high modulation frequency.

Results:

On the Catphan©600 phantom in the first study, the method reduces the error of the CT number in the selected regions of interest (ROIs) from 371.4 to 21.9 Hounsfield units (HU); the contrast to noise ratio also increases from 10.9 to 19.2. On the anthropomorphic chest phantom in the second study, which represents a more difficult case due to the high scatter signals and object heterogeneity, the method reduces the error of the CT number from 327 to 19 HU in the selected ROIs and from 31.4% to 5.7% on the overall average. The third study is to investigate the impact of object size on the efficiency of our method. The scatter‐to‐primary ratio estimation error on the Catphan©600 phantom without any annulus (20 cm in diameter) is at the level of 0.04, it rises to 0.07 and 0.1 on the phantom with an elliptical annulus (30 cm in the minor axis and 38 cm in the major axis) and with a circular annulus (38 cm in diameter).

Conclusions:

On the three phantom studies, good scatter correction performance of the proposed method has been demonstrated using both image comparisons and quantitative analysis. The theory and experiments demonstrate that a strong primary modulation that possesses a low transmission factor and a high modulation frequency is preferred for high scatter correction accuracy.
Anciently Asexual Bdelloid Rotifers Escape Lethal Fungal Parasites by Drying Up and Blowing Away
Authors: Wilson Christopher G. , Sherman Paul W.
Published: January 2010

Sex Avoidance Strategy

In metazoans, sex, as a means of reproduction, is almost universal, with popular theories suggesting that the high rate of genome mixing that sex promotes helps protect us from deleterious mutations and/or rapidly evolving parasites. Asexual organisms are both rare and often evolutionarily short-lived. If this rarity is due to failure to deal with parasites, then bdelloid rotifers, which have been abstaining from sex for millions of years, must be able to dodge the parasite bullet in some arrange-other way.
Wilson and Sherman
(p.
574
; see the cover) suggest that bdelloid rotifers do so by being both so resistant to desiccation and so amenable to dispersal on the air that their parasites can neither survive such punishing conditions nor spread as far nor as fast, allowing the asexual bdelloids to start afresh in (parasite-free) pastures anew.
Direct Restart of a Replication Fork Stalled by a Head-On RNA Polymerase
Authors: Pomerantz Richard T. , O’Donnell Mike
Published: January 2010

When Polymerases Collide

Genomes must be replicated by DNA polymerase and copied by RNA polymerase. The two processes occur concurrently in bacteria and, although the majority of bacterial genes are co-oriented with replication, head-on collisions still occur and can result in double-strand breaks in the genome.
Pomerantz and O'Donnell
(p.
590
) show, in vitro, that both
Escherichia coli
DNA and RNA polymerases grind to a halt when they collide bumper to bumper but that the replication fork remains intact, with the RNA polymerase being shunted off the DNA and out of the way. Mfd, a transcription-repair coupling factor, promotes DNA replication restart probably by rewinding separated DNA stands ahead of the halted transcription complex, promoting its displacement from the DNA.
Coexistence of Quiescent and Active Adult Stem Cells in Mammals
Authors: Li Linheng , Clevers Hans
Published: January 2010

In the (Stem Cell) Zone

Efforts to isolate and characterize various types of stem cells have revealed much about the molecular mechanisms of stem cell self-renewal and differentiation, as well as the function of the microenvironment, or stem cell niche.
Li and Clevers
(p.
542
) review what is known about stem cells in the hair follicle, bone marrow, and intestinal epithelium and suggest that two stem cell populations, one that is quiescent and one that is actively in the cell cycle, may coexist in these tissues in a so-called “zoned” stem cell model.
A Basal Alvarezsauroid Theropod from the Early Late Jurassic of Xinjiang, China
Authors: Choiniere Jonah N. , Xu Xing , Clark James M. , Forster Catherine A. , Guo Yu , Han Fenglu
Published: January 2010

Big Finger

Alvarezsauroidea are an enigmatic group of theropods presumed to be closely related to birds, though most specimens are younger than
Archaeopteryx
.

Choiniere
et al.

(p.
571
; see news story by Stone) now describe a more complete early specimen, dating to about 160 million years ago, which supports the conclusion that Alvarezsauroidea are a basal group of the clade containing both birds and their close theropod relatives. The fossil also helps to reveal the evolution of this group's peculiar forelimb, which includes one enlarged functional finger.
Making Genetics Easy to Understand
Authors: Stark Louisa A. , Pompei Kevin
Published: January 2010

An integrated pair of Web sites for students and teachers supports genetics and genomics education worldwide.
Role of ABA and ABI3 in Desiccation Tolerance
Authors: Khandelwal A. , Cho S. H. , Marella H. , Sakata Y. , Perroud P.-F. , Pan A. , Quatrano R. S.
Published: January 2010

The hormone pathway that stabilizes seeds may have served more primitive seedless plants in supporting desiccation tolerance.
The Politics of Geoengineering
Authors: Blackstock Jason J. , Long Jane C. S.
Published: January 2010

Nations commencing geoengineering research must commit to full international collaboration and transparency.
Making Sense of Printed Symbols
Reading in the Brain
The Science and Evolution of a Human Invention

by Stanislas Dehaene

Viking, New York, 2009. 400 pp. $27.95, C$35. ISBN 9780670021109.
Authors: Gross Charles G.
Published: January 2010

Dehaene discusses neurological, cognitive, evolutionary, and cultural aspects of reading.
Of Locusts and Scientists

Heuschrecken [Locusts]
by Stefan Kaegi; scenography by Dominic Huber; music by Bo Wiget

Rimini Protokoll. Schauspielhaus Zürich, October 2009. HAU Berlin, 28 March to 10 April 2010. www.rimini-protokoll.de/website/en/project_4200.html
Authors: Laubichler Manfred D. , Honegger Gitta
Published: January 2010

Rimini Protokoll explores the biology of migratory locusts, the lives of scientists who study them, and the relations between the researchers and their subjects.
Science Education Web Sites
Authors: Alberts Bruce
Published: January 2010

In this issue, we announce the first of 12 winners of a competition for web sites that best promote science education. Each month this year,
Science
will publish an essay by the creators of a winning Web site that describes their online resource. This month's featured site focuses on teaching and learning genetics, and it originates from the University of Utah (see p. 538). The
Science
Prize for Online Resources in Education (SPORE) recognizes outstanding freely available online materials that enrich science education. There were nearly 100 entries for 2009 from many nations. They spanned diverse subjects, ranging from astronomy, chemistry, and physics to geology and biology. Most sites targeted students, ranging from elementary through graduate school, whereas others focused on the general public. Many included videos, animations, real-world data sets, or teaching materials.
Pathogen Microevolution in High Resolution
Authors: Aziz Ramy K. , Nizet Victor
Published: January 2010

The application of next-generation high-throughput genotyping technologies, as illustrated in a recent analysis of a highly resistant
Staphylococcus aureus
strain, can provide new clues on the geographical origin and intrahospital spread of important microbial pathogens.
Obesity and Inflammation: The Fas Connection
Authors: Cheng Elaine
Published: January 2010

The death receptor Fas may contribute to obesity-induced inflammation and the pathogenesis of type 2 diabetes mellitus.
In SituImmunolocalization and Stage-Dependent Expression of a Secretory Serine Protease inLeishmania donovaniand Its Role as a Vaccine Candidate
Authors: Choudhury Rajdeep , Das Partha , Bhaumik Siddhartha Kumar , De Tripti , Chakraborti Tapati
Published: January 2010

Proteases have been found to play essential roles in many biological processes, including the pathogenesis of leishmaniasis. Most parasites rely on their intracellular and extracellular protease repertoire to invade and multiply in mammalian host cells. However, few studies have addressed serine proteases inLeishmaniaand their role in host pathogenesis. Here we report the intracellular distribution of a novelL. donovanisecretory serine protease in the flagellar pocket, as determined by immunogold labeling. Flow cytometry and confocal immunofluorescence analysis revealed that the expression of the protease diminishes sequentially from virulent to attenuated strains of this species and is also highly associated with the metacyclic stage ofL. donovanipromastigotes. The level of internalization of parasites treated with the anti-115-kDa antibody into host macrophages was significantly reduced from that of non-antibody-treated parasites, suggesting that this serine protease probably plays a role in the infection process.In vivostudies confirmed that this serine protease is a potential vaccine candidate. Altogether, the 115-kDa serine protease might play vital roles inL. donovanipathogenesis and hence could be recognized as a potential candidate for drug design.
Phenotypic Definition of Effector and Memory T-Lymphocyte Subsets in Mice Chronically Infected withMycobacterium tuberculosis
Authors: Henao-Tamayo Marcela I. , Ordway Diane J. , Irwin Scott M. , Shang Shaobin , Shanley Crystal , Orme Ian M.
Published: January 2010

The bacteriumMycobacterium tuberculosisremains one of the world's most successful pathogens, a situation that is aggravated by the fact that the existing vaccine,Mycobacterium bovisBCG, is not effective in adults. As with any vaccine, the purpose of giving BCG vaccination is to establish a long-lived state of memory immunity, but whether this is successfully completely established is still unclear. It is generally accepted that memory T cells can be divided into central and effector memory populations by function and by phenotype; however, the majority of data supporting this division have been generated using transgenic mouse models or mice that have recovered from acute viral infections. Tuberculosis, on the other hand, represents a persistent, chronic state of immunity in which the presence of memory T cells is far less well defined. We show here that mice vaccinated with BCG or chronically infected withM. tuberculosisestablish antigen-specific populations of cells within the lungs that predominantly express a cellular phenotype consistent with their being effector or effector memory cells. In contrast, cells with a central memory phenotype exist in much lower numbers in the lungs but can be found in significantly larger numbers in the spleen, where they may represent a potential reservoir. These data suggest that the effector-to-central-memory T-cell transition may well be minimal in these persisting mycobacterial infections, and they support a novel hypothesis that this may explain the fundamental basis of the failure of the BCG vaccine in humans.
Prime-Boost Immunization Using a DNA Vaccine Delivered by Attenuated
Salmonella enterica
Serovar Typhimurium and a Killed Vaccine Completely Protects Chickens from H5N1 Highly Pathogenic Avian Influenza Virus
Authors: Pan Zhiming , Zhang Xiaoming , Geng Shizhong , Fang Qiang , You Meng , Zhang Lei , Jiao Xinan , Liu Xiufan
Published: January 2010

H5N1 highly pathogenic avian influenza virus (HPAIV) has posed a great threat not only for the poultry industry but also for human health. However, an effective vaccine to provide a full spectrum of protection is lacking in the poultry field. In the current study, a novel prime-boost vaccination strategy against H5N1 HPAIV was developed: chickens were first orally immunized with a hemagglutinin (HA) DNA vaccine delivered by attenuated
Salmonella enterica
serovar Typhimurium, and boosting with a killed vaccine followed. Chickens in the combined vaccination group but not in single vaccination and control groups were completely protected against disease following H5N1 HPAIV intranasal challenge, with no clinical signs and virus shedding. Chickens in the prime-boost group also generated significantly higher serum hemagglutination inhibition (HI) titers and intestinal mucosal IgA titers against avian influenza virus (AIV) and higher host immune cellular responses than those from other groups before challenge. These results demonstrated that the prime-boost vaccination strategy provides an effective way to prevent and control H5N1 highly pathogenic avian influenza virus.
Serum Bactericidal Antibody Response 1 Year after Meningococcal Polysaccharide Vaccination of Patients with Common Variable Immunodeficiency
Authors: Rezaei Nima , Siadat Seyed Davar , Aghamohammadi Asghar , Moin Mostafa , Pourpak Zahra , Norouzian Dariush , Mobarakeh Jalal Izadi , Aghasadeghi Mohammad Reza , Nejati Mehdi , Read Robert C.
Published: January 2010

Some patients with common variable immunodeficiency (CVID) can generate an antibody response following vaccination with
Neisseria meningitidis
polysaccharide, but the duration of this protection is unknown. In this study, serum bactericidal antibody (SBA) responses to serogroup C
N. meningitidis
of 23 patients with CVID and 23 sex- and age-matched controls were measured 1 year after vaccination with the plain A/C meningococcal polysaccharide vaccine. The fold rise in serum bactericidal antibody geometric mean titers of the control group from prevaccination to 1 year postvaccination was significantly higher than that of the patient group (5.41- versus 2.96-fold,
P
= 0.009). Of 23 CVID patients, 8 had a poor response to vaccine (<4-fold rise) 3 weeks after vaccination, and low titers remained when measured 1 year later. Of the 15 CVID patients who had a normal response to vaccine (≥4-fold rise) 3 weeks after vaccination, 6 cases failed to maintain protective SBA titers, whereas the remaining 9 had protective titers 1 year after vaccination. Only one of the 23 controls, who developed protective SBA titers after 3 weeks, lost the protective titers after 1 year. Among the patients, the presence of bronchiectasis and/or splenomegaly at enrollment was associated with poor SBA response to vaccine at 3 weeks and/or failure to maintain protective levels at 1 year. The results of this study demonstrate that a number of CVID patients can produce protective antibody titers that can persist for 1 year after vaccination, which lends strong support to the inclusion of polysaccharide vaccine in the immunization program for CVID patients.
Characterization of
Slackia exigua
Isolated from Human Wound Infections, Including Abscesses of Intestinal Origin
Authors: Kim Keun-Sung , Rowlinson Marie-Claire , Bennion Robert , Liu Chengxu , Talan David , Summanen Paula , Finegold Sydney M.
Published: January 2010

Eleven clinical strains isolated from infected wound specimens were subjected to polyphasic taxonomic analysis. Sequence analysis of the 16S rRNA gene showed that all 11 strains were phylogenetically related to
Slackia exigua
. Additionally, conventional and biochemical tests of 6 of the 11 strains were performed as supplementary methods to obtain phenotypic identification by comparison with the phenotypes of the relevant type strains.
S. exigua
has been considered an oral bacterial species in the family
Coriobacteriaceae
. This organism is fastidious and grows poorly, so it may easily be overlooked. The 16S rRNA gene sequences and the biochemical characteristics of four of the
S. exigua
strains isolated for this study from various infections indicative of an intestinal source were almost identical to those of the validated
S. exigua
type strain from an oral source and two of the
S. exigua
strains from oral sources evaluated in this study. Thus, we show for the first time that
S. exigua
species can be isolated from extraoral infections as well as from oral infections. The profiles of susceptibility to selected antimicrobials of this species were also investigated for the first time.
Analytical Performance Characteristics and Clinical Utility of a Novel Assay for Total Hepatitis C Virus Core Antigen Quantification
Authors: Ross R. S. , Viazov S. , Salloum S. , Hilgard P. , Gerken G. , Roggendorf M.
Published: January 2010

The detection and quantification of hepatitis C virus (HCV) core antigen in serum or plasma by the use of different assay formats have previously been shown to represent useful markers of viral replication. In the present study, the intrinsic performance characteristics and the potential clinical utility of a novel assay for the quantification of total HCV core antigen were comprehensively assessed by using clinical serum samples and specimens contained in various evaluation panels. The Architect HCV Ag assay showed a specificity of 100%. The intra- and interassay coefficients of variation ranged from 3.6 to 8.0% and from 4.7 to 9.5%, respectively. Except for HCV genotype 2 isolates, the analytical sensitivity was always less than 10 fmol core antigen/liter, corresponding to approximately 500 to 3,000 IU of HCV RNA/ml. Linearity was guaranteed throughout the dynamic range (10 to 20,000 fmol/liter). When seroconversion panels were tested, the assay was not inferior to HCV RNA detection and reduced the preseroconversion period by 4 to 16 days. The results obtained by core antigen and HCV RNA quantification for 385 clinical specimens were correlated by regression analysis (
r
= 0.857), but the calculated conversion equation differed significantly from the line of identity. Monitoring of viral kinetics by use of either core antigen or RNA concentrations in 38 HCV-infected patients undergoing antiviral combination therapy resulted in very similarly shaped curves in all cases. Finally, the Architect HCV Ag assay was also shown to enable high-throughput screening of
in vitro
HCV RNA replication. With these results taken together, the Architect HCV Ag assay proved to be a specific, reproducible, highly sensitive, and clinically applicable test format which will find its future place in the context of virological HCV diagnostics.
Association of Serotypes of
Streptococcus pneumoniae
with Age in Invasive Pneumococcal Disease
Authors: Imöhl Matthias , Reinert Ralf René , Ocklenburg Christina , van der Linden Mark
Published: January 2010

A total of 7,764 isolates from patients with invasive pneumococcal disease (IPD) were collected from 1992 to June 2006. Data on serotypes were available for 5,022 isolates (64.7% of all invasive isolates). Some 54.0% of the isolates originated from adults ≥16 years of age, and 46.0% were from children <16 years of age. The leading serotypes were 14, 23F, 1, 6B, 7F, 3, and 4. The serotypes significantly more common in children were 14, 6B, 19F, and 18C, while among adults, serotypes 3 and 4 were predominant. Serotype 7F was statistically more prevalent among children <4 months old than among the other age groups. Among children aged ≥4 months and <1 year, serotype 19F occurred statistically more frequently; and among children aged ≥1 year to <5 years, serotypes 14, 6B, and 18C were overrepresented. The serotypes predominantly affecting patients younger than the remaining collective of patients were 14, 6B, 19F, and 18C, while patients with IPD caused by serotypes 3, 4, and 9V were older than the collective, on average.
Aminoglycoside Resistance and Susceptibility Testing Errors in
Acinetobacter baumannii-calcoaceticus
Complex
Authors: Akers Kevin S. , Chaney Chris , Barsoumian Alice , Beckius Miriam , Zera Wendy , Yu Xin , Guymon Charles , Keen Edward F. , Robinson Brian J. , Mende Katrin , Murray Clinton K.
Published: January 2010

Antimicrobial resistance is depleting the pharmacopeia of agents clinically useful against Gram-negative bacilli. As the number of active agents diminishes, accurate susceptibility testing becomes critical. We studied the susceptibilities of 107 isolates of the
Acinetobacter baumannii-calcoaceticus
complex to amikacin, gentamicin, and tobramycin using disk diffusion, Etest, as well as the Phoenix, Vitek 2, and MicroScan automated systems, and compared the results to those obtained by broth microdilution. Genes encoding aminoglycoside-modifying enzymes (AMEs) were detected by multiplex PCR, and clonal relationships were determined by pulsed-field gel electrophoresis. Tobramycin was the most active aminoglycoside (27.1% of isolates were susceptible). Disk diffusion and Etest tended to be more accurate than the Vitek 2, Phoenix, and MicroScan automated systems; but errors were noted with all methods. The Vitek 2 instrument incorrectly reported that more than one-third of the isolates were susceptible to amikacin (a very major error). Isolates were polyclonal, with 26 distinct strains, and carried multiple AME genes unrelated to the strain type. The presence of the
ant(2")-Ia
gene was statistically associated with resistance to each aminoglycoside. The AME genotype accounted for the resistance profile observed in a minority of isolates, suggesting the involvement of multiple resistance mechanisms. Hospital pharmacy records indicated the preferential use of amikacin over other aminoglycosides in the burn intensive care unit, where aminoglycoside resistance is prevalent. The resistance in that unit did not correlate with a predominant strain, AME genotype, or total annual aminoglycoside consumption. Susceptibility to tobramycin increased, even though susceptible isolates carried AME genotypes predicting the inactivation of tobramycin. Determination of the relative contribution of multiple concurrent resistance mechanisms may improve our understanding of aminoglycoside resistance in the
Acinetobacter baumannii-calcoaceticus
complex.
Major Differences Exist in Frequencies of Virulence Factors and Multidrug Resistance between Community and Nosocomial
Escherichia coli
Bloodstream Isolates
Authors: Cooke Niamh M. , Smith Stephen G. , Kelleher Mary , Rogers Thomas R.
Published: January 2010

Escherichia coli
is a major cause of bloodstream infections and death due to sepsis. It is the most frequent Gram-negative bacterial pathogen recovered from cultures of blood from both community-acquired and nosocomial cases. We set out to determine the relationships between
E. coli
virulence factors (VFs), phylogenetic groups, and antibiotic resistance and whether bacteremia cases had a community, health care-associated. or nosocomial origin. Isolates from consecutive episodes of
E. coli
bacteremia in 303 patients presenting to a university hospital were screened for their VFs, phylogenetic group, and antibiotic resistance. The majority of VFs present in the collection were equally distributed between antibiotic-susceptible and multiple-drug-resistant (MDR) isolates, but the overall VF score was higher for isolates of community and health care-associated origin than those of nosocomial origin (
P
= 0.0002 and
P
= 0.0172, respectively); the
papA
,
papG
allele II,
hlyA
, and
hek
VFs were more prevalent in this cohort. Most isolates belonged to phylogenetic group B2, which harbored a greater proportion of antibiotic-susceptible isolates than MDR isolates (
P
= 0.04). The community, health care-associated, or nosocomial origin of
E. coli
bacteremia determines the virulence capacity of an isolate better than the phylogenetic group does. This study provides new insights into the relationships between the pathogenesis and epidemiology of
E. coli
bacteremia.
Achromobacter xylosoxidans
Genomic Characterization and Correlation of Randomly Amplified Polymorphic DNA Profiles of Cystic Fibrosis Patients
Authors: Magni Annarita , Trancassini Maria , Varesi Paola , Iebba Valerio , Curci Anna , Pecoraro Claudia , Cimino Giuseppe , Schippa Serena , Quattrucci Serena
Published: January 2010

Achromobacter xylosoxidans
is an emerging pathogen increasingly being isolated from respiratory samples of cystic fibrosis (CF) patients. Its role and clinical significance in lung pathogenesis have not yet been clarified. The aim of the present study was to genetically characterize
A. xylosoxidans
strains isolated from CF patients by use of randomly amplified polymorphic DNA (RAPD) profiles and to look for a possible correlation between RAPD profiles and the patients' clinical features, such as their spirometry values, the presence of concomitant chronic bacterial flora at the time of isolation, and the persistent or intermittent presence of
A. xylosoxidans
strains. A set of 106 strains of
A. xylosoxidans
were typed by RAPD analysis, and their profiles were analyzed by agglomerative hierarchical classification (AHC) and associated with the patient characteristics mentioned above by factorial discriminant analysis (FDA). The overall results obtained in this study showed that (i) there is a marked genetic relationship between strains isolated from the same patients at different times, (ii) characteristic RAPD profiles are associated with different predicted classes for forced expiratory volume in 1 s (FEV1%), (iii) some characteristic RAPD profiles are associated with different concomitant chronic flora (CCF) profiles, and (iv) there is a significant division of RAPD profiles into “persistent strains” and “intermittent strains” of
A. xylosoxidans
. These findings seem to imply that the lung habitats found in CF patients are capable of shaping and selecting the colonizing bacterial flora, as seems to be the case for the
A. xylosoxidans
strains studied.