bluuebunny/crossref_metadata_2025 huggingface dataset:
Details of the Computed Flowfield Over a Circular Cylinder at Reynolds Number 1200
Authors: Rumsey C. L.
Published: October 2009

The application of an upwind-biased implicit approximate factorization Navier-Stokes algorithm to the unsteady impulsive start-up flow over a circular cylinder at Reynolds number 1200 is described. The complete form of the compressible Navier-Stokes equations is used, and the algorithm is second-order accurate in both space and time. The drag on the cylinder is computed for early times in the start-up flow. The value of the local maximum drag as well as the time at which it occurs are predicted and compared to another computational result and experiment. The development with time of the shape and size of the separated vortical flow region is computed, as well as the time-variation of several boundary layer parameters and profile shapes. Computations, in general, show excellent agreement with experiment, although the present method predicts a more rapid onset of reversed flow on the cylinder than evidenced in experiment. The effect of grid density on the development of the unsteady flow is also shown.
Dosimetric characterization of round HDR AccuBoost applicators for breast brachytherapy
Authors: Rivard Mark J. , Melhus Christopher S. , Wazer David E. , Bricault Raymond J.
Published: October 2009

Purpose:

The AccuBoost brachytherapy system applies HDR beams peripherally to the breast using collimating applicators. The purpose of this study was to benchmark Monte Carlo simulations of the HDR source, to dosimetrically characterize the round applicators using established Monte Carlo simulation and radiation measurement techniques and to gather data for clinical use.

Methods

: Dosimetric measurements were performed in a polystyrene phantom, while simulations estimated dose in air, liquid water, polystyrene and ICRU 44 breast tissue. Dose distribution characterization of the 4–8 cm diameter collimators was performed using radiochromic EBT film and air ionization chambers.

Results:

The central axis dose falloff was steeper for the 4 cm diameter applicator in comparison to the 8 cm diameter applicator, with surface to 3 cm depth‐dose ratios of 3.65 and 2.44, respectively. These ratios did not considerably change when varying the phantom composition from breast tissue to polystyrene, phantom thickness from 4 to 8 cm, or phantom radius from 8 to 15 cm. Dose distributions on the central axis were fitted to sixth‐order polynomials for clinical use in a hand calculation spreadsheet (i.e., nomogram). Dose uniformity within the useful applicator apertures decreased as depth‐dose increased.

Conclusions:

Monte Carlo benchmarking simulations of the HDR source using the MCNP5 radiation transport code indicated agreement within 1% of the published results over the radial/angular region of interest. Changes in phantom size and radius did not cause noteworthy changes in the central axis depth‐dose. Polynomial fit depth‐dose curves provide a simple and accurate basis for a nomogram.
Neurotransmission SPECT and MR registration combining mutual and gradient information
Authors: Bullich S. , Ros D. , Pavía J. , Cot A. , López N. , Catafau A. M.
Published: October 2009

Purpose:

Image registration is important in functional image analysis. In neurotransmission single photon emission tomography (nSPECT), specific uptake sites can be accurately localized by superimposing the SPECT study onto a high‐resolution structural image such as a magnetic resonance (MR) of the subject. Mutual‐information (MI)‐based algorithms are usually employed for this purpose. Nevertheless, nSPECT/MR registration using MI is often limited by the low count rates present in nSPECT. Several works have proposed extensions of the MI measures to include gradient information (GI) from the images but their performance has not been evaluated in SPECT studies.

Methods:

In this work, the accuracy of the MI including gradient information (MIG) was compared with the standard MI using data from healthy volunteers and data simulating a specific uptake reduction using three different radioligands:, , .

Results:

The results showed that MIG‐based registration yielded better accuracy than MI. The MIG‐based similarity measures were less sensitive to sparse sampling and diminished computational time without a substantial decrease in registration accuracy.

Conclusions:

Accuracy of nSPECT/MR registration is improved when gradient information is included in the MI‐based algorithm, which makes MIG‐based registration potentially useful for clinical applications.
Enhanced imaging of microcalcifications in digital breast tomosynthesis through improved image‐reconstruction algorithms
Authors: Sidky Emil Y. , Pan Xiaochuan , Reiser Ingrid S. , Nishikawa Robert M. , Moore Richard H. , Kopans Daniel B.
Published: October 2009

Purpose:

The authors develop a practical, iterative algorithm for image‐reconstruction in undersampled tomographic systems, such as digital breast tomosynthesis (DBT).

Methods:

The algorithm controls image regularity by minimizing the image total variation (TpV), a function that reduces to the total variation when or the image roughness when . Constraints on the image, such as image positivity and estimated projection‐data tolerance, are enforced by projection onto convex sets. The fact that the tomographic system is undersampled translates to the mathematical property that many widely varied resultant volumes may correspond to a given data tolerance. Thus the application of image regularity serves two purposes: (1) Reduction in the number of resultant volumes out of those allowed by fixing the data tolerance, finding the minimum image TpV for fixed data tolerance, and (2) traditional regularization, sacrificing data fidelity for higher image regularity. The present algorithm allows for this dual role of image regularity in undersampled tomography.

Results:

The proposed image‐reconstruction algorithm is applied to three clinical DBT data sets. The DBT cases include one with microcalcifications and two with masses.

Conclusions:

Results indicate that there may be a substantial advantage in using the present image‐reconstruction algorithm for microcalcification imaging.
Determination of output factors for stereotactic radiosurgery beams
Authors: Fan J. , Paskalev K. , Wang L. , Jin L. , Li J. , Eldeeb A. , Ma C.
Published: October 2009

Accurate dosimetry of the narrow beam tends to be difficult to perform due to the absence of lateral electronic equilibrium and the steep dose gradient, as well as the finite size of detectors. Thus, although the high dose rate 6 MV beam on the VARIAN Trilogy accelerator is increasingly utilized for stereotactic radiosurgery (SRS) treatment, there is no general agreement in the SRS beam output factor values among the Trilogy user community. Trilogy SRS beams are confined by cone collimators and the available collimator sizes range from 5 and 10 to 30 mm, in every 2 mm increment. A range of the relative output factors are in clinic use. This variation may impair observations of dose response and optimizations of the prescribed dose. It is necessary to investigate an accurate, easily performable, and detector independent method for the narrow beam output factor measurement. In this study, a scanning beam/scanning chamber method was proposed to overcome the limitation/difficulty of using a relatively large detector in narrow beam output factor measurement. Specifically, for the scanning beam method, multiple narrow beams are used for the dose measurement using a finite size chamber. These multiple scanning beams form an equivalent large uniform field which provides lateral electron equilibrium condition. After the measurement, the contributions from neighboring beams are deconvolved and the value is used for output factor determinations. For a Linac that cannot move a beam laterally, the scanning chamber method can be used to achieve the same result. The output factors determined in such a method were compared to chambers (a 0.015 cc PTW PinPoint ion chamber and a 0.125 cc PTW ion chamber) and film measurement, as well as with Monte Carlo simulation. Film and Monte Carlo results are found to be in excellent agreement with the measurement using the scan beam method. However, the VARIAN recommended output factors measured directly by Wellhöfer CC01 chamber and Scanditronix photon field diode are consistently higher for all the cones. Especially for the 5 mm cone, the difference is more than 10%. Overall, the results suggested that the new method can help overcoming the detector volume averaging effect and the positioning uncertainties, which constitute the major challenge in small radiosurgical beam output factor measurement, and provide reliable output factors.
Experimental validation of Monte Carlo (MANTIS) simulated x‐ray response of columnar CsI scintillator screens
Authors: Freed Melanie , Miller Stuart , Tang Katherine , Badano Aldo
Published: October 2009

Purpose:

MANTIS is a Monte Carlo code developed for the detailed simulation of columnar CsI scintillator screens in x‐ray imaging systems. Validation of this code is needed to provide a reliable and valuable tool for system optimization and accurate reconstructions for a variety of x‐ray applications. Whereas previous validation efforts have focused on matching of summary statistics, in this work the authors examine the complete point response function (PRF) of the detector system in addition to relative light output values.

Methods:

Relative light output values and high‐resolution PRFs have been experimentally measured with a custom setup. A corresponding set of simulated light output values and PRFs have also been produced, where detailed knowledge of the experimental setup and CsI:Tl screen structures are accounted for in the simulations. Four different screens were investigated with different thicknesses, column tilt angles, and substrate types. A quantitative comparison between the experimental and simulated PRFs was performed for four different incidence angles (0°, 15°, 30°, and 45°) and two different x‐ray spectra (40 and 70 kVp). The figure of merit (FOM) used measures the normalized differences between the simulated and experimental data averaged over a region of interest.

Results:

Experimental relative light output values ranged from 1.456 to 1.650 and were in approximate agreement for aluminum substrates, but poor agreement for graphite substrates. The FOMs for all screen types, incidence angles, and energies ranged from 0.1929 to 0.4775. To put these FOMs in context, the same FOM was computed for 2D symmetric Gaussians fit to the same experimental data. These FOMs ranged from 0.2068 to 0.8029. Our analysis demonstrates that MANTIS reproduces experimental PRFs with higher accuracy than a symmetric 2D Gaussian fit to the experimental data in the majority of cases. Examination of the spatial distribution of differences between the PRFs shows that the main reason for errors between MANTIS and the experimental data is that MANTIS‐generated PRFs are sharper than the experimental PRFs.

Conclusions:

The experimental validation of MANTIS performed in this study demonstrates that MANTIS is able to reliably predict experimental PRFs, especially for thinner screens, and can reproduce the highly asymmetric shape seen in the experimental data. As a result, optimizations and reconstructions carried out using MANTIS should yield results indicative of actual detector performance. Better characterization of screen properties is necessary to reconcile the simulated light output values with experimental data.
Treatment response assessment of breast masses on dynamic contrast‐enhanced magnetic resonance scans using fuzzy ‐means clustering and level set segmentation
Authors: Shi Jiazheng , Sahiner Berkman , Chan Heang‐Ping , Paramagul Chintana , Hadjiiski Lubomir M. , Helvie Mark , Chenevert Thomas
Published: October 2009

The goal of this study was to develop an automated method to segment breast masses on dynamic contrast‐enhanced (DCE) magnetic resonance (MR) scans and to evaluate its potential for estimating tumor volume on pre‐ and postchemotherapy images and tumor change in response to treatment. A radiologist experienced in interpreting breast MR scans defined a cuboid volume of interest (VOI) enclosing the mass in the MR volume at one time point within the sequence of DCE‐MR scans. The corresponding VOIs over the entire time sequence were then automatically extracted. A new 3D VOI representing the local pharmacokinetic activities in the VOI was generated from the 4D VOI sequence by summarizing the temporal intensity enhancement curve of each voxel with its standard deviation. The method then used the fuzzy ‐means (FCM) clustering algorithm followed by morphological filtering for initial mass segmentation. The initial segmentation was refined by the 3D level set (LS) method. The velocity field of the LS method was formulated in terms of the mean curvature which guaranteed the smoothness of the surface, the Sobel edge information which attracted the zero LS to the desired mass margin, and the FCM membership function which improved segmentation accuracy. The method was evaluated on 50 DCE‐MR scans of 25 patients who underwent neoadjuvant chemotherapy. Each patient had pre‐ and postchemotherapy DCE‐MR scans on a 1.5 T magnet. The in‐plane pixel size ranged from 0.546 to 0.703 mm and the slice thickness ranged from 2.5 to 4.5 mm. The flip angle was 15°, repetition time ranged from 5.98 to 6.7 ms, and echo time ranged from 1.2 to 1.3 ms. Computer segmentation was applied to the coronal T1‐weighted images. For comparison, the same radiologist who marked the VOI also manually segmented the mass on each slice. The performance of the automated method was quantified using an overlap measure, defined as the ratio of the intersection of the computer and the manual segmentation volumes to the manual segmentation volume. Pre‐ and postchemotherapy masses had overlap measures of and , respectively. The percentage volume reduction (PVR) estimated by computer and the radiologist were and , respectively. Paired Student's test indicated that the difference between the mean PVRs estimated by computer and the radiologist did not reach statistical significance . The automated mass segmentation method may have the potential to assist physicians in monitoring volume change in breast masses in response to treatment.
Liquid crystal display response time estimation for medical applications
Authors: Elze Tobias , Tanner Thomas G.
Published: October 2009

Purpose:

Accurate characterization of diagnosis instruments is crucial in medical applications such as radiology and clinical neurosciences. While classical CRT medical displays have been replaced almost exclusively with liquid crystal devices (LCDs), the assessment of their temporal properties (response times) is still largely based on heuristic methods, which have not been evaluated thoroughly yet. The authors introduce a novel approach and show that it improves the accuracy and reliability compared to the common heuristic recommended by ISO 9241‐305 substantially for a wide range of settings.

Methods:

The approach is based on disentangling the signal from the modulatory backlight through division (division approach). They evaluated this method in two different ways: First, they applied both methods to luminance transition measurements of different LCD monitors. Second, they simulated LCD luminance transitions by modeling the LCD optical responses according to a physical liquid crystal director orientation model. The simulated data were generated for four different response times, each with four different backlight modulation frequencies. Both the novel and the ISO convolution method were applied to the data.

Results:

Application of the methods to the simulated data shows a bias of up to 46% for the ISO approach, while the novel division approach is biased at most 2%. In accordance with the simulations, estimates for real measurements show differences in the two approaches of more than 200% for some LCD panels.

Conclusion:

The division approach is robust against periodic backlight fluctuations and can reliably estimate even very short response times or small transitions. Unlike the established method, it meets the accuracy requirements of medical applications. In contrast, the popular convolution approach for estimating response times is prone to misestimations of time by several orders of magnitude and tend to further worsen as advances in LCD technology lead to shorter response times.
Dosimetric comparison of , , and radiocolloids in craniopharyngioma treatments
Authors: Sadeghi Mahdi , Karimi Elham , Hosseini S. Hamed
Published: October 2009

Purpose:

In the radionuclide treatment of some forms of brain tumors such as craniopharyngiomas, the selection of the appropriate radionuclide for therapy is a key element in treatment planning. The aim was to study the influence by considering the beta‐emitter radionuclide dose rate in an intracranial cyst.

Methods:

Dosimetry was performed using the MCNP4C radiation transport code. Analytical dosimetry was additionally performed using the Loevinger and the Berger formulas in the MATLAB software. Each result was compared under identical conditions. The advantages and disadvantages of using versus and were investigated.

Results:

The dose rate at the inner surface of the cyst wall was estimated to be for a concentration of . Under identical conditions of treatment, the corresponding dose rates were for and for . For a well‐defined cyst radius and identical wall thickness, higher dose rates resulted for .

Conclusions:

To achieve the same radiological burden, the required amount of physical activity of injectable solution is lower for. This is found to be a consequence of both the radionuclide physical half‐life and the pattern of energy deposition from the emitted radiation. According to the half‐life and dose‐rate results, would be a good substitute for .
AAPM recommendations on dose prescription and reporting methods for permanent interstitial brachytherapy for prostate cancer: Report of Task Group 137
Authors: Nath Ravinder , Bice William S. , Butler Wayne M. , Chen Zhe , Meigooni Ali S. , Narayana Vrinda , Rivard Mark J. , Yu Yan
Published: October 2009

During the past decade, permanent radioactive source implantation of the prostate has become the standard of care for selected prostate cancer patients, and the techniques for implantation have evolved in many different forms. Although most implants use or sources, clinical use of sources has also recently been introduced. These sources produce different dose distributions and irradiate the tumors at different dose rates. Ultrasound was used originally to guide the planning and implantation of sources in the tumor. More recently, CT and/or MR are used routinely in many clinics for dose evaluation and planning. Several investigators reported that the tumor volumes and target volumes delineated from ultrasound, CT, and MR can vary substantially because of the inherent differences in these imaging modalities. It has also been reported that these volumes depend critically on the time of imaging after the implant. Many clinics, in particular those using intraoperative implantation, perform imaging only on the day of the implant. Because the effects of edema caused by surgical trauma can vary from one patient to another and resolve at different rates, the timing of imaging for dosimetry evaluation can have a profound effect on the dose reported (to have been delivered), i.e., for the same implant (same dose delivered), CT at different timing can yield different doses reported. Also, many different loading patterns and margins around the tumor volumes have been used, and these may lead to variations in the dose delivered. In this report, the current literature on these issues is reviewed, and the impact of these issues on the radiobiological response is estimated. The radiobiological models for the biological equivalent dose (BED) are reviewed. Starting with the BED model for acute single doses, the models for fractionated doses, continuous low‐dose‐rate irradiation, and both homogeneous and inhomogeneous dose distributions, as well as tumor cure probability models, are reviewed. Based on these developments in literature, the AAPM recommends guidelines for dose prescription from a physics perspective for routine patient treatment, clinical trials, and for treatment planning software developers. The authors continue to follow the current recommendations on using and as the primary quantities, with more specific guidelines on the use of the imaging modalities and the timing of the imaging. The AAPM recommends that the postimplant evaluation should be performed at the optimum time for specific radionuclides. In addition, they encourage the use of a radiobiological model with a specific set of parameters to facilitate relative comparisons of treatment plans reported by different institutions using different loading patterns or radionuclides.
Influence of Tigecycline on Expression of Virulence Factors in Biofilm-Associated Cells of Methicillin-Resistant
Staphylococcus aureus
Authors: Smith Karen , Gould Katherine A. , Ramage Gordon , Gemmell Curtis G. , Hinds Jason , Lang Sue
Published: October 2009

Methicillin-resistant
Staphylococcus aureus
(MRSA) infections are complicated by the ability of the organism to grow in surface-adhered biofilms on a multitude of abiotic and biological surfaces. These multicellular communities are notoriously difficult to eradicate with antimicrobial therapy. Cells within the biofilm may be exposed to a sublethal concentration of the antimicrobial due to the metabolic and phenotypic diversity of the biofilm-associated cells or the protection offered by the biofilm structure. In the present study, the influence of a sublethal concentration of tigecycline on biofilms formed by an epidemic MRSA-16 isolate was investigated by transcriptome analysis. In the presence of the drug, 309 genes were upregulated and 213 genes were downregulated by more than twofold in comparison to the levels of gene regulation detected for the controls not grown in the presence of the drug. Microarray data were validated by real-time reverse transcription-PCR and phenotypic assays. Tigecycline altered the expression of a number of genes encoding proteins considered to be crucial for the virulence of
S. aureus
. These included the reduced expression of
icaC
, which is involved in polysaccharide intercellular adhesin production and biofilm development; the upregulation of
fnbA
,
clfB
, and
cna
, which encode adhesins which attach to human proteins; and the downregulation of the
cap
genes, which mediate the synthesis of the capsule polysaccharide. The expression of
tst
, which encodes toxic shock syndrome toxin 1 (TSST-1), was also significantly reduced; and an assay performed to quantify TSST-1 showed that the level of toxin production by cells treated with tigecycline decreased by 10-fold (
P
< 0.001) compared to the level of production by untreated control cells. This study suggests that tigecycline may reduce the expression of important virulence factors in
S. aureus
and supports further investigation to determine whether it could be a useful adjunct to therapy for the treatment of biofilm-mediated infections.
Φm46.1, the Main
Streptococcus pyogenes
Element Carrying
mef
(A) and
tet
(O) Genes
Authors: Brenciani Andrea , Bacciaglia Alessandro , Vignaroli Carla , Pugnaloni Armanda , Varaldo Pietro E. , Giovanetti Eleonora
Published: October 2009

Φm46.1, the recognized representative of the most common variant of mobile, prophage-associated genetic elements carrying resistance genes
mef
(A) (which confers efflux-mediated erythromycin resistance) and
tet
(O) (which confers tetracycline resistance) in
Streptococcus pyogenes
, was fully characterized. Sequencing of the Φm46.1 genome (55,172 bp) demonstrated a modular organization typical of tailed bacteriophages. Electron microscopic analysis of mitomycin-induced Φm46.1 revealed phage particles with the distinctive icosahedral head and tail morphology of the
Siphoviridae
family. The chromosome integration site was within a 23S rRNA uracil methyltransferase gene. BLASTP analysis revealed that the proteins of Φm46.1 had high levels of amino acid sequence similarity to the amino acid sequences of proteins from other prophages, especially Φ10394.4 of
S. pyogenes
and λSa04 of
S. agalactiae
. Phage DNA was present in the host cell both as a prophage and as free circular DNA. The lysogeny module appears to have been split due to the insertion of a segment containing
tet
(O) (from integrated conjugative element 2096-RD.2) and
mef
(A) (from a Tn
1207.1
-like transposon) into the unintegrated phage DNA. The phage attachment sequence lies in the region between
tet
(O) and
mef
(A) in the unintegrated form. Thus, whereas in this form
tet
(O) is ∼5.5 kb upstream of
mef
(A), in the integrated form,
tet
(O), which lies close to the right end of the prophage, is ∼46.3 kb downstream of
mef
(A), which lies close to the left end of the prophage.
Klebsiella pneumoniae
AcrAB Efflux Pump Contributes to Antimicrobial Resistance and Virulence
Authors: Padilla Emma , Llobet Enrique , Doménech-Sánchez Antonio , Martínez-Martínez Luis , Bengoechea José Antonio , Albertí Sebastián
Published: October 2009

Respiratory infections caused by
Klebsiella pneumoniae
are characterized by high rates of mortality and morbidity. Management of these infections is often difficult, due to the high frequency of strains that are resistant to multiple antimicrobial agents. Multidrug efflux pumps play a major role as a mechanism of antimicrobial resistance in Gram-negative pathogens. In the present study, we investigated the role of the
K. pneumoniae
AcrRAB operon in antimicrobial resistance and virulence by using isogenic knockouts deficient in the AcrB component and the AcrR repressor, both derived from the virulent strain 52145R. We demonstrated that the AcrB knockout was more susceptible, not only to quinolones, but also to other antimicrobial agents, including β-lactams, than the wild-type strain and the AcrR knockout. We further showed that the AcrB knockout was more susceptible to antimicrobial agents present in human bronchoalveolar lavage fluid and to human antimicrobial peptides than the wild-type strain and the AcrR knockout. Finally, the AcrB knockout exhibited a reduced capacity to cause pneumonia in a murine model, in contrast to the wild-type strain. The results of this study suggest that, in addition to contributing to the multidrug resistance phenotype, the AcrAB efflux pump may represent a novel virulence factor required for
K. pneumoniae
to resist innate immune defense mechanisms of the lung, thus facilitating the onset of pneumonia.
An Albumin-Conjugated Peptide Exhibits Potent Anti-HIV Activity and LongIn VivoHalf-Life
Authors: Xie Dong , Yao Cheng , Wang Li , Min Wenjie , Xu Jiahong , Xiao Jiahai , Huang Mingxian , Chen Bo , Liu Bin , Li Xiaolin , Jiang He
Published: October 2009

The clinical application of conventional peptide drugs often is limited by their shortin vivohalf-life and potential immunogenicity. Frequent injection presents challenges to the treatment of chronic diseases, such as HIV infection. We chemically modified a peptide HIV fusion inhibitor with 3-maleimidopropionic acid (MPA), which allows rapid and irreversible conjugation with serum albumin at a 1:1 molar ratio. FB006M, with an MPA modification at the 13th amino acid, rapidly formed conjugate with albumin upon intravenous injection, and it exhibited a remarkably extendedin vivohalf-life. The albumin conjugate of FB006M displayed potent inhibitory activity against a number of laboratory and clinical isolates of HIV-1in vitroandin vivo. No immunogenicity or antibody formation was detected after repeated dosing. The clinical application of FB006M may decrease the cost of treatment and improve treatment compliance and patient quality of life.
Genetic Fusions of Heat-Labile (LT) and Heat-Stable (ST) Toxoids of Porcine EnterotoxigenicEscherichia coliElicit Neutralizing Anti-LT and Anti-STa antibodies
Authors: Zhang Weiping , Zhang Chengxian , Francis David H. , Fang Ying , Knudsen David , Nataro James P. , Robertson Donald C.
Published: October 2009

EnterotoxigenicEscherichia coli(ETEC) strains are a major cause of diarrheal disease in humans and farm animals.E. colifimbriae, or colonization factor antigens (CFAs), and enterotoxins, including heat-labile enterotoxins (LT) and heat-stable enterotoxins (ST), are the key virulence factors in ETEC diarrhea. Unlike fimbriae or LT, STa has not often been included as an antigen in development of vaccines against ETEC diarrhea because of its poor immunogenicity. STa becomes immunogenic only after being coupled with a strongly immunogenic carrier protein. However, native or shorter STa antigens either had to retain toxic activity in order to become antigenic or elicited anti-STa antibodies that were not sufficiently protective. In this study, we genetically mutated the porcine LT (pLT) gene for a pLT192(R→G)toxoid and the porcine STa (pSTa) gene for three full-length pSTa toxoids [STa11(N→K), STa12(P→F), and STa13(A→Q)] and used the full-length pLT192as an adjuvant to carry the pSTa toxoid for pLT192:pSTa-toxoid fusion antigens. Rabbits immunized with pLT192:pSTa12or pLT192:pSTa13fusion protein developed high titers of anti-LT and anti-STa antibodies. Furthermore, rabbit antiserum and antifecal antibodies were able to neutralize purified cholera toxin (CT) and STa toxin. In addition, preliminary data suggested that suckling piglets born by a sow immunized with the pLT192:pSTa13fusion antigen were protected when challenged with an STa-positive ETEC strain. This study demonstrated that pSTa toxoids are antigenic when fused with a pLT toxoid and that the elicited anti-LT and anti-STa antibodies were protective. This fusion strategy could provide instructive information to develop effective toxoid vaccines against ETEC-associated diarrhea in animals and humans.
A Monoclonal Immunoglobulin G Antibody Directed against an Immunodominant Linear Epitope on the Ricin A Chain Confers Systemic and Mucosal Immunity to Ricin
Authors: Neal Lori M. , O'Hara Joanne , Brey Robert N. , Mantis Nicholas J.
Published: October 2009

Due to the potential use of ricin and other fast-acting toxins as agents of bioterrorism, there is an urgent need for the development of safe and effective antitoxin vaccines. A candidate ricin subunit vaccine (RiVax) consisting of a recombinant attenuated enzymatic A chain (RTA) has been shown to elicit protective antitoxin antibodies in mice and rabbits and is currently being tested in phase I human clinical trials. However, evaluation of the efficacy of this vaccine for humans is difficult for a number of reasons, including the fact that the key neutralizing B-cell epitopes on RTA have not been fully defined. Castelletti and colleagues (Clin. Exp. Immunol.136:365-372, 2004) recently identified a linear epitope on RTA, spanning residues L161 to I175, as a primary target of serum antibodies derived from humans who had been treated with ricin immunotoxin. While affinity-purified polyclonal IgG antibodies against this region of RTA were capable of neutralizing ricinin vitro, their capacity to confer protection against ricin challengein vivowas not determined. In this report, we describe the production and characterization of GD12, a murine monoclonal IgG1 antibody specifically directed against residues 163 to 174 (TLARSFIICIQM) of RTA. GD12 bound ricin holotoxin with high affinity (KD[dissociation constant], 2.9 × 10−9M) and neutralized it with a 50% inhibitory concentration of ∼0.25 μg/ml, as determined by a Vero cell-based cytotoxicity assay. Passive administration of GD12 was sufficient to protect BALB/c mice against intraperitoneal and intragastric ricin challenges. These data are important in terms of vaccine development, since they firmly establish that preexisting serum antibodies directed against residues 161 to 175 on RTA are sufficient to confer both systemic and mucosal immunity to ricin. The potential of GD12 to serve as a therapeutic following ricin challenge was not explored in this study.
Development of Immunoglobulin M Memory to Both a T-Cell-Independent and a T-Cell-Dependent Antigen following Infection withVibrio choleraeO1 in Bangladesh
Authors: Kendall Emily A. , Tarique Abdullah A. , Hossain Azim , Alam Mohammad Murshid , Arifuzzaman Mohammad , Akhtar Nayeema , Chowdhury Fahima , Khan Ashraful I. , LaRocque Regina C. , Harris Jason B. , Ryan Edward T. , Qadri Firdausi , Calderwood Stephen B.
Published: October 2009

Vibrio choleraeO1 can cause severe watery diarrhea that can be life-threatening without treatment. Infection results in long-lasting protection against subsequent disease. Development of memory B cells of the immunoglobulin G (IgG) and IgA isotypes toV. choleraeO1 antigens, including serotype-specific lipopolysaccharide (LPS) and the B subunit of cholera toxin (CTB), after cholera infection has been demonstrated. Memory B cells of the IgM isotype may play a role in long-term protection, particularly against T-cell-independent antigens, but IgM memory has not been studied inV. choleraeO1 infection. Therefore, we assayed acute- and convalescent-phase blood samples from cholera patients for the presence of memory B cells that produce cholera antigen-specific IgM antibody upon polyclonal stimulation in in vitro culture. We also examined the development of serological and antibody-secreting cell responses following infection. Subjects developed significant IgM memory responses by day 30 after infection, both to the T-cell-independent antigen LPS and to the T-cell-dependent antigen CTB. No significant corresponding elevations in plasma IgM antibodies or circulating IgM antibody-secreting cells to CTB were detected. In 17 subjects followed to day 90 after infection, significant persistence of elevated IgM memory responses was not observed. The IgM memory response to CTB was negatively correlated with the IgG plasma antibody response to CTB, and there was a trend toward negative correlation between the IgM memory and IgA plasma antibody responses to LPS. We did not observe an association between the IgM memory response to LPS and the vibriocidal titer.
The effect of non-contingent and accurate performance feedback on pacing and time trial performance in 4-km track cycling
Authors: Mauger A R , Jones A M , Williams C A
Published: October 2009

Objective

To determine whether the provision of comparative performance feedback during 4 km track cycling affects completion time.

Design

Five highly trained male cyclists first performed a baseline (BL) 4-km time trial (TT) on a velodrome track, followed by two further randomised 4-km TT, during which riders received either correct (COR) or non-contingent (FAL) feedback based on their BL performance.

Results

Participants completed the COR TT in a significantly faster time (t4=−3.10, p<0.05) than the FAL TT (341 (8) s vs 350 (12) s). Over the TT, a significant difference in mean speed was apparent between the two conditions (F15,60=1.95, p<0.05) on the second (t4=4.71, p<0.05), 15th (t4=3.45, p<0.05) and final lap (t4=3.30, p<0.05).

Conclusion

The significant difference in completion time and pacing strategy between the two conditions suggests that accurate, comparative performance feedback is beneficial to performance, especially during the start and end of an exercise bout. The results support the previously unfounded assumption that performance feedback is advantageous during exercise and highlights the importance of an athlete's support team during an event.
Setting standards for the prevention and management of travellers’ diarrhoea in elite athletes: an audit of one team during the Youth Commonwealth Games in India
Authors: Tillett E , Loosemore M
Published: October 2009

Objective:

Devise and implement evidence-based guidelines for the prevention and management of travellers’ diarrhoea (TD), and establish the incidence of TD during an elite sporting trip to India.

Design:

Literature review and audit.

Setting:

Youth Commonwealth Games in India 2008.

Participants:

All members of the Team England Squad.

Main outcome measures:

Hygiene guidelines included only drinking bottled water, eating hot food and regular hand washing with alcohol gel. Ciprofloxacin was offered to non-athlete team members as prophylaxis but not to athletes due to its possible association with tendon disease. Following implementation of these guidelines, the incidence of travellers’ diarrhoea (TD) in the whole squad was 24/122 (20%), compared with 7/14 (50%) on the reconnaissance trip (preguidelines). In those taking prophylactic ciprofloxacin, the incidence was 4/33 (12%), compared with 20/89 (23%) in those not taking ciprofloxacin. No athlete missed their event due to TD.

Conclusions:

The incidence of TD was less during the event than on the reconnaissance trip. The relative contribution to this reduction in strict hygiene guidelines as compared with potentially improved catering hygiene arrangements is unknown. Prophylactic ciprofloxacin also reduced the incidence of TD but it is probably not appropriate for use in elite athletes. Rifaximin may be an alternative for this group.
Primary myxoid liposarcoma of the thyroid gland
Authors: Huang G W , Li Y X , Hu Z L
Published: October 2009

Primary myxoid liposarcoma of the thyroid gland is extremely rare. This report describes such a case. A 59-year-old woman was admitted for evaluation of a 6×6×5 cm nodule in the left lobe of the thyroid gland. Left thyroid lobectomy was performed without any postoperative treatment except for follow-up. Osseous and pulmonary metastasis developed 1 year later and the patient died 15 months after the surgery. The clinical course and treatment choice are discussed.
EGFR fluorescence in situ hybridisation assay: guidelines for application to non-small-cell lung cancer
Authors: Varella-Garcia M , Diebold J , Eberhard D A , Geenen K , Hirschmann A , Kockx M , Nagelmeier I , Rüschoff J , Schmitt M , Arbogast S , Cappuzzo F
Published: October 2009

There is a need for predictive biomarkers that identify non-small-cell lung cancer (NSCLC) patients most likely to respond to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment. There are numerous potential candidates, although none has been proven in prospective clinical trials. The EGFR gene copy number evaluated by fluorescence in situ hybridisation (FISH) has been highlighted as one of the most effective markers for sensitivity to EGFR TKIs in large phase III, randomised placebo-controlled trials and has been used in clinical settings to assist physicians in defining the therapeutic regimen. The EGFR FISH assay has technical challenges and it is critical that detailed guidelines are provided to help clinical laboratories in performing and interpreting the test. Excellent assay reproducibility and portability rates among laboratories are crucial to guarantee that accurate clinical decisions can be made for patients with NSCLC. This article discusses the consensus outcomes of a global workshop convened to discuss key technical issues and standardise reading strategies for the EGFR FISH assay of NSCLC tumour tissue.
Proteins from the Wnt pathway are involved in the pathogenesis and progression of mammary phyllodes tumours
Authors: Karim R Z , Gerega S K , Yang Y H , Horvath L , Spillane A , Carmalt H , Scolyer R A , Lee C S
Published: October 2009

Background:

The Wnt pathway is important in cell signalling transduction and is involved in the pathogenesis of multiple tumour types. A comprehensive analysis of the expression of Wnt signalling pathway proteins in mammary phyllodes tumours (PTs) has not been previously performed.

Aims:

To evaluate the immunohistochemical expression of Wnt pathway proteins in a cohort of PTs, to determine their role in tumour pathogenesis and to identify any associations with patient outcome.

Methods:

65 PTs (34 benign, 23 borderline and 8 malignant) diagnosed at a single institution between 1990 and 2006 were analysed. Immunohistochemical stains were performed on tissue microarrays for β-catenin, Wnt1, Wnt5a, SFRP4 and E-cadherin. Stroma and epithelium were scored separately.

Results:

Stromal cytoplasmic Wnt5a and SFRP4 expression showed significant progressive increases in expression with increasing grade (p = 0.002 and p = 0.02 respectively). Epithelial membranous and stromal nuclear β-catenin, epithelial cytoplasmic Wnt1 and epithelial E-cadherin all also showed increasing expression with increasing tumour grade, however, the differences were not significant. Disease-free survival was significantly decreased (p = 0.0017) with positive epithelial E-cadherin staining.

Conclusions:

Results suggest that alterations in the Wnt pathway are important in the progression and in the epithelial and stromal interactions in PTs. They have important implications for understanding the pathogenesis of these uncommon but clinically important tumours.
Heart transplant biopsies: interpretation and significance
Authors: Nair V , Butany J
Published: October 2009

The endomyocardial biopsy(EMB) is a valuable tool that is inadequately utilised, except in monitoring orthotopic, homograft, heart grafts. Performed on a regular, programmed schedule, or on an emergent basis when needed, the EMB is the gold standard for monitoring graft function ( with regard to cellular rejection), often before clinical symptoms develop. This paper addresses these points and discusses handling of tissues and some studies for possible antibody mediated rejection when the lack of morphologic features of cellular rejection does not fit with the patients clinical presentation, days or months after the surgical procedure. In the hands of a skilled operator the EMB procedure is relatively painless and free of signicicant complications.
AN EXPLICIT SOLUTION FOR COMPUTING THE VERTICES OF THE EUCLIDEAN d-DIMENSIONAL VORONOI DIAGRAM OF SPHERES IN A FLOATING-POINT ARITHMETIC
Authors: GAVRILOVA MARINA L.
Published: October 2009

The problem of computing a d-dimensional Euclidean Voronoi diagram of spheres is relevant to many areas, including computer simulation, motion planning, CAD, and computer graphics. This paper presents a new algorithm based on the explicit computation of the coordinates and radii of Euclidean Voronoi diagram vertices for a set of spheres. The algorithm is further applied to compute the Voronoi diagram with a specified precision in a fixed length floating-point arithmetic. The algorithm is implemented using the ECLibrary (Exact Computation Library) and tested on the example of a 3-dimensional Voronoi diagram of a set of spheres.
NEW RESULTS FROM H.E.S.S. OBSERVATIONS OF GALAXY CLUSTERS
Authors:   FOR THE H.E.S.S. COLLABORATION, DOMAINKO WILFRIED , NEDBAL DALIBOR , HINTON JAMES A. , MARTINEAU-HUYNH OLIVIER
Published: October 2009

Clusters of galaxies are believed to contain a significant population of cosmic rays. From the radio and probably hard X-ray bands it is known that clusters are the spatially most extended emitters of non-thermal radiation in the Universe. Due to their content of cosmic rays, galaxy clusters are also potential sources of VHE (> 100 GeV) gamma rays. Recently, the massive, nearby cluster Abell 85 has been observed with the H.E.S.S. experiment in VHE gamma rays with a very deep exposure as part of an ongoing campaign. No significant gamma-ray signal has been found at the position of the cluster. The non-detection of this object with H.E.S.S. constrains the total energy of cosmic rays in this system. For a hard spectral index of the cosmic rays of -2.1 and if the cosmic-ray energy density follows the large scale gas density profile, the limit on the fraction of energy in these non-thermal particles with respect to the total thermal energy of the intra-cluster medium is 8% for this particular cluster. This value is at the lower bounds of model predictions.
GAMMA-RAY BURST DETECTION WITH ICECUBE
Authors:   for the IceCube Collaboration, KAPPES ALEXANDER
Published: October 2009

With their narrow emission window gamma-ray bursts (GRBs) are among the most promising objects for the first identification of high-energy cosmic neutrinos. If a considerable fraction of the ultra-high energy cosmic rays is indeed produced in GRBs, IceCube, which is now more than half-way completed, should be able to detect the associated neutrinos in the next few years. Furthermore, optical follow-up observations of neutrino multiplets will enhance IceCube's sensitivity to choked GRBs which do not produce a gamma-ray signal.
VERY HIGH ENERGY ACTIVE GALACTIC NUCLEI SYNCHROTRON SELF-COMPTON MODELING TOUR
Authors: LENAIN J.-P. , BOISSON C. , SOL H. , DANIEL M. K. , CHADWICK P. M. , WARD M. J.
Published: October 2009

The current very high energy (VHE; E > 100 GeV ) experiments have tremendously increased the number of detected extragalactic sources. We present a synchrotron self-Compton modeling tour of the active galactic nuclei currently established as VHE emitters so far, and investigate possible correlations among the intrinsic and derived parameters.
THE LEPTONIC MODEL FOR BLAZAR EMISSION
Authors: MASTICHIADIS APOSTOLOS
Published: October 2009

The leptonic model has become the standard method of fitting the multiwavelength spectra of blazars. In what follows we review the basic premises of the model, giving emphasis on the evolution of its key ideas and assumptions.
HADRON-INITIATED EMISSION PROCESSES IN BLAZAR JETS
Authors: REIMER ANITA
Published: October 2009

Despite many advances in AGN physics, observationally as well as theoretically, the relativistic matter composition of extragalactic jets remains concealed. In contrast to the so called leptonic AGN emission models, hadronic models consider relativistic protons to be present in those sources, in addition to the relativistic electrons and positrons, and possibly cold material. Here I briefly discuss most processes that are commonly believed to characterize the so-called hadronic AGN emission models, and these include leptonic as well as hadronic processes. As an application predictions for the neutrino output during the TeV-flare of 3C 279 in 2006 are provided.
MULTI-MESSENGER ASTRONOMY WITH CENTAURUS A
Authors: KACHELRIEß M. , OSTAPCHENKO S. , TOMÀS R.
Published: October 2009

We calculated for the nearest active galactic nucleus (AGN), Centaurus A (Cen A), the flux of high energy cosmic rays and of accompanying secondary photons and neutrinos expected from hadronic interactions in the source. We used as two basic models for the generation of ultrahigh energy cosmic rays (UHECR) shock acceleration in the radio jet and acceleration in the regular electromagnetic field close to the core of the AGN, normalizing the UHECR flux to the observations of the Auger experiment. Here we compare the previously obtained photon fluxes with the recent data reported by the Fermi LAT and H.E.S.S. collaborations. In the case of the core model, we find good agreement both for the predicted spectral shape and the overall normalization between our earlier results and the H.E.S.S. observations for a primary proton energy dN/dE ∝ E-α with α ~ 2 or smaller. A broken power law with high-energy part α = -2.7 leads to photon fluxes in excess of the Fermi measurements. The energy spectrum of the photon fluxes obtained by us for the jet scenario is in all cases at variance with the H.E.S.S. and Fermi observations.
ULTRA-HIGH ENERGY COSMIC RAY AND NEUTRINO DETECTION USING THE MOON: FIRST RESULTS
Authors: SCHOLTEN O. , BACELAR J. , SINGH K. , AL YAHYAOUI R. , BUITINK S. , FALCKE H. , BRAUN R. , DE BRUYN A. G. , STROM R. G. , STAPPERS B.
Published: October 2009

We show that at wavelengths comparable to the length of the shower produced by an Ultra-High Energy cosmic ray or neutrino, radio signals are an extremely efficient way to detect these particles. First results are presented of an analysis of 20 hours of observation data for NuMoon project using the Westerbork Synthesis Radio Telescope to search for short radio pulses from the Moon.