bluuebunny/crossref_metadata_2025 huggingface dataset:
Poster — Thur Eve — 12: Evaluation of an Electron Monte Carlo Dose Calculation Algorithm for Treatment Planning
Authors: Chamberland E , Lachance B , Beaulieu L
Published: August 2010

Purpose: To evaluate the accuracy of the electron Monte Carlo (eMC) dose calculation algorithm included in the Eclipse treatment planning system. Method and Materials: Multiple tests were planned to explore the system behaviour in configurations encountered in clinical practices. The first series of test were performed in a homogeneous water phantom. Measured and eMC calculated dose distributions were compared for different combinations of energy/applicator/depth. Three different inhomogeneous solid phantoms simulating high and low density materials were constructed to explore various heterogeneity conditions: a small air cylinder, a lung phantom and a chest wall phantom. In this work, the lung phantom, which consists of cork slabs, is described in details. In all cases, comparisons are made between measurements, carried out by means of XV‐2 films, and eMC and Pinnacle computations. Finally, the evaluation of the eMC algorithm for clinical case, a nose cancer, was conducted. Results: The eMC validation in the water phantom and in the lung phantom is shown to be accurate. The maximum observed discrepancy between measurements and eMC is only 2.5%. For the lung case, Pinnacle does not correctly model the electron scattering. The retrospective study of the clinical case, which presents scatter perturbations by air cavities, shows planar dose difference up to 20% between Pinnacle and eMC. Conclusion: eMC algorithm showed good agreements with measurements in simple homogeneous and heterogeneous phantoms. Comparatively to the electron pencil beam algorithms of Pinnacle, the eMC calculations more precisely predict large dose perturbations due to inhomogeneities.
Poster — Thur Eve — 14: Pretreatment IMRT QA Program for Low‐Dose Control Points Based on Dynamic Noise Correction Using a 2D Matrix of Ionization Chambers
Authors: Grigorov G , Chow J , Fleck A
Published: August 2010

We developed a pre‐treatment intensity modulated radiation therapy (IMRT) QA program for verification of low‐dose control points registered by a 2D matrix of ionization chambers (ICs). The program eliminates the dose error caused by the induced reading or noise for every chamber electrically. It was found that the low‐dose deviation was in the rate of 20–40% outside the field (i.e. in the volume of the normal tissue). Moreover, the voxel‐to‐voxel dose was found to have non‐uniform deviation, which increased linearly with time. The rates of the electrically induced chamber readings were 0.3–1.3 cGy per 0.5 minute, when a beam of 100 monitor units using dose rate equal to 300 MU/min with consideration of the time for the leaf motion, was used in the irradiation with time > 20 s. This means that if low dose point (3–5 cGy) is registered by an IC of the highest induced readings (1.3 cGy), the deviation between the planned and delivered doses would be in the rate of 40−25%. Comparison of the fluence maps may be affected by the non‐uniformly induced dose readings. A field function depending on the beam irradiation time to correct the registered dose profile is therefore needed. In this study, a pre‐treatment IMRT QA program fully based on absolute dose measurements has been established. The program includes a comparison between the calculated and measured doses. The electrically induced readings of the 2D matrix were subtracted from the beam dose map to correct the measurements.
Poster — Thur Eve — 24: Variable Field Strength MR System for Hyperpolarized Noble Gas Imaging of Rodent Lungs
Authors: Dominguez‐Viqueira W , Fox M , Carias M , Santyr G
Published: August 2010

The optimum field strength for hyperpolarized noble gas lung (129Xe and 3He) imaging depends on the sample/coil size and field‐dependence of the lung properties (i.e. relaxation times, susceptibility effects), and has been predicted to correspond to low field strengths (0.05–0.2T) for clinical studies. For the case of the small coils typically used for rodent lung imaging, it has been previously shown that the maximum SNR is expected to be at high fields (>3T). However, the SNR advantage of higher fields for rodent lung imaging can potentially be offset by improved coil design using Litz wire coils resulting in comparable SNR at low fields. In this work, a broad‐band variable field (0.01–0.15T) MR system is described, as well as experiments to validate the hyperpolarized noble gas image SNR dependence on field strength. The coil performance at 0.866MHz and 2.385MHz, corresponding to 129Xe and 3He frequencies at 73.5mT respectively, was optimized using multi‐turn Litz wire coils. The 129Xe and 3He image SNR of rat lung was investigated theoretically and in vivo, at 73.5mT and compared to images obtained at 3 T. Due to the improvement provided by the multi‐turn Litz coils, the SNR at 3T was predicted to be a factor of two higher compared to 73.5mT, this compares to a factor of about ten for single‐turned copper coils. In conclusion, hyperpolarized noble gas lung image quality in rats is comparable between 73.5mT and 3T, with the use of Litz wires together with the long T2* available at low magnetic field strength.
Poster — Thur Eve — 28: Feasibility Study for Open Door Low Energy Treatments Using Maze‐Type Bunkers Designed for Dual Energy Linacs
Authors: Evans MDC , Kildea J , Beckham W , Parker W , Podgorsak EB
Published: August 2010

Older bunkers designed for dual energy linacs were often constructed with both a maze and high energy door. The door provides both radiation safety and access control, however, it may be desirable to limit use of the high energy door to reduce mechanical wear and improve workflow. We conducted a feasibility study to determine if our high energy linac (Varian 21EX with electrons and 6/18 MV photons) located in a bunker with a maze and high energy door could be operated with the door closed for 18 MV beams only. Dose estimation using NCRP‐151, followed by measurement with TLD and survey meters was carried out. Workload and use factors from literature, and from realistic data derived from our ARIA database were used. NCRP‐151 calculations underestimated the measured value, and this discrepancy became worse for points further into the maze. For our workload of 7 000 Gy m2/year an equal gantry angle distribution suggests 1.0 mSv extra per year, while a realistic workload and use factor derived from our database suggests 0.1 mSv extra per year for the 6 MV door‐open scenario. A door occupancy factor of 0.125 further reduces these estimates. The worst case In‐Any‐One‐Hour Time Averaged Dose‐Equivalent Rate was determined to be 0.84 mSv/hr. A Last‐Person‐Out system linked to a light guard in parallel with a energy‐select logic system was bench tested. Adapting existing high energy bunkers designed with maze and door for operation with the door closed for high energy photon beams only is a viable option.
Poster — Thur Eve — 33: A Dose‐Based Metric for Evaluation of Image Registration Accuracy
Authors: Heath E , Kawrakow I
Published: August 2010

Current approaches for the valuation of image registration accuracy rely on comparison of calculated point displacements with measured motion of manually identified anatomical landmarks or contours. In the context of using image registration to map dose distributions, the interpretation of a landmark analysis in terms of a dose error is not readily obvious. In this work we propose a new method to evaluate image registration accuracy based on a dose mapping error. The dose error is calculated by comparing two different dose mapping approaches which use the same deformation vectors but one scores the energy deposited on the target geometry while the other scores energy deposition on a deformed reference geometry. Any error in the deformation vectors will lead to a discrepancy between these geometries and a difference in the warped dose distribution. The dose warping error was evaluated on a set of inhale and exhale images for a lung patient. Multiple image registrations were performed with different levels of registration accuracy. At each landmark point the dose warping error was computed as well as a simplified dose error calculated from the landmark error and the dose gradient. A comparison of dose mapping error and landmark error revealed that the latter is not sufficient to predict the accuracy of the dose warping and factors such as the smoothness of the deformations must be considered. The proposed dose mapping error can be readily applied to determine the accuracy of image registrations used in treatment planning applications.
Poster — Thur Eve — 42: Anti‐Scatter Grid Use for Digital Tomosynthesis: An Observer Study
Authors: King JM , Elbakri IA , Reed M , Wrogemann J
Published: August 2010

In digital imaging, an anti‐scatter grid can be placed between the patient and digital detector to improve image contrast, but including the grid also increases the dose to the patient by 2–5 times, depending on the patient thickness. This is of particular concern in the pediatric population because children are more radiosensitive than adults. Since smaller patients produce less scatter, the grid is sometimes removed when imaging small children in order to reduce the dose. However, the default machine protocols at our institution recommend using a grid at most pediatric patient sizes for digital tomosynthesis imaging. We hypothesized that because of the image reconstruction process of tomosynthesis, the final images may be less sensitive to scatter than digital radiography (DR), in which case we should be able to remove the grid for a wide range of pediatric patient sizes without sacrificing a significant level of image quality. To test our hypothesis, we performed an image quality rating study on DR and tomosynthesis images taken with and without the grid for a variety of simulated patient thicknesses. We found that the reconstructed tomosynthesis images did not show a significant reduction in scatter sensitivity compared to DR. Our results suggested that, in general, the grid should be used for all tomosynthesis imaging where the patient thickness is greater than approximately 10 cm. Research supported by GE Healthcare.
Poster — Thur Eve — 47: Automatic Comparison of Portal Images for the Detection of Radiotherapy Treatment Delivery Errors
Authors: Lee R , Tran M , McCurdy B , Pistorius S
Published: August 2010

The goal of this project is to develop a real‐time automatic comparison tool to detect portal dose image errors and has two logical parts:

1. A mechanism to detect the presence of a significant discrepancy.

2. A set of components to identify the probable cause(s) of the discrepancy including geometrical positioning errors as well as machine specific delivery errors.

Initially, we have only considered in‐plane rotations and translations. A total of ∼700 portal images of an anthropomorphic pelvic phantom were obtained using a Varian aS1000 EPID. The images contained combinations of three types of geometrical patient set‐up errors. The angle of rotation (about the axis perpendicular to the EPID) was varied from [−5, +5] degrees and the translational distance was varied from [−10, +10] mm. The majority of the images were acquired from the AP direction however ∼130 images were of a lateral view. The system was found to be sensitive to in‐plane rotations down to ∼ 2°, out of plane rotations greater than ∼4° and displacements 3mm. For the lateral views, the calculated rotation was correct to within 1/2° and translations to within 5mm 53% of the time. Considering only translations, the accuracy increases to ∼82%. The results are much better for the AP views. The in‐plane rotation was within ±1/2deg; for all cases and the displacement error was greater than 1.5 mm in only 1 case. The system was able to analyze an image pair in ∼10s, however, no effort was put toward optimization of the system.
Poster — Thur Eve — 49: Investigating the Effects of Motion on Texture within the Lung
Authors: Markel D , Caldwell C , Sun A , Hamideh A , Vines D
Published: August 2010

Automated methods using CT‐image‐based texture features have shown promise for segmentation of lung tumours. Combining CT with PET features for use in segmentation has been shown to improve segmentation accuracy compared to using either modality separately and has potential for use in accurate internal target volume definition in lung cancer. One issue of particular importance in lung tumor segmentation is the effect of motion on the measures extracted from PET and CT images. This aspect is under investigation using maximum intensity projections (MIPs) in addition to temporally gated CT, PET and un‐gated PET data sets. Preliminary results from 13 patients (9 diagnosed with lung cancer; 4 diagnosed with cancers outside the lung area, representing healthy lung tissue) show that with gated CT, PET and CT homogeneity, PET Entropy, and CT Coarseness are some of the strongest discriminators for use in classification with statistical distance measures of up to 2.0 between normal and abnormal tissue. The texture features from MIPs of 4 of the patients show that they present somewhat less discriminating feature values, as to be expected. Their usefulness within the context of segmentation remains to be investigated.
Poster — Thur Eve — 57: Use of a Micro Liquid Ionization Chamber for Commissioning of Radiosurgery Beams
Authors: Patrocinio H , Evans M , Ruo R , Soisson E , AlDahlawi I , Seuntjens J
Published: August 2010

A commercially available liquid ionization chamber (PTW, Freiburg, Germany) was used in the commissioning of stereotactic radiosurgery beams for a Novalis Tx linear accelerator. The chamber has a small collecting volume (0.002cm3) yet providing a relatively high signal for its size. The chamber was attached to a solitary electrometer for output measurements, and to a water scanning system for PDD and beam profile measurements. The commissioning set consisted of output factors, percentage depth doses and off‐axis beam profiles for six collimator sizes ranging from 4mm to 15mm in diameter. The measured data was compared to both Gafchromic film dosimetry measurements and to data from the literature. Output factors measured with the liquid ion chamber are in good agreement with film measurements (<2% difference, except for 3.8% difference for the 4mm collimator). Similar overall agreement was found with a recent publication by Fan et al.,(2009). Beam profile measurements were found to be in very good agreement with Gafchromic film measurements. Our PDD data was equally in reasonable agreement with data from a recent publication by Chang et al., (2008) with discrepancies of 2–3% observed. A comparison of TMRs calculated from our PDD data and from direct measurement revealed larger differences, increasing with depth, that have yet to be resolved. The liquid ion chamber was easy to use required only a brief pre‐irradiation to provide a stable signal. Our preliminary results suggest this high spatial resolution chamber has usefulness in small field measurements.
Poster — Thur Eve — 59: Improving Treatment Delivery Efficiency in Lung SBRT with a VMAT Approach
Authors: Comsa D , Purdie TG , Moseley D
Published: August 2010

Lung SBRT has demonstrated excellent local control and low toxicity for patients with medically inoperable, early stage non‐small‐cell lung cancer (NSCLC). The promising clinical lung SBRT results have been achieved using a variety of hypofractionated dose regimens and localization/immobilization techniques; however treatment delivery times have been consistently long. Volumetric modulated arc therapy (VMAT) is a variable dose rate delivery method which has the potential for increased treatment delivery efficiency, as it allows continuous irradiation of the target with the gantry rotating around the patient. A retrospective planning study (n = 10) demonstrates VMAT as a promising technique to produce dose distributions similar or, in most cases, superior to those achieved with the 3D conformai SBRT plans currently used in our clinic for early stage NSCLC treatments. Single arc and non‐coplanar 2 arc VMAT approaches lead to improved conformity of both the high and low dose around the target and lower V20 and V5 values for the healthy lung. In spite of the significantly increased number of monitor units for the VMAT plans, this study shows treatment delivery time improvements (n = 2) of 45% for the single arc configurations compared with 3D conformai static delivery. A second non‐coplanar partial arc can be used to further increase conformity of the high dose surrounding the target and better avoid organs at risk, with a delivery efficiency improvement of 25% for the 2‐arc configurations compared with static delivery. Finally, treatment delivery accuracy with VMAT was similar to that of conformal static plans.
Inherit the ER
Authors: Wong Wei
Published: August 2010

A MAPK pathway delays cytokinesis in yeast if the mother cell is undergoing ER stress.
Making an Active Choice
Authors: Adler Elizabeth M.
Published: August 2010

Calcium spiking can regulate neurotransmitter specification through c-Jun–dependent modulation of
tlx3
expression.
Trypanocidal Activity of Aziridinyl Nitrobenzamide Prodrugs
Authors: Bot Chris , Hall Belinda S. , Bashir Noosheen , Taylor Martin C. , Helsby Nuala A. , Wilkinson Shane R.
Published: August 2010

The trypanocidal agents nifurtimox and benznidazole both function as prodrugs and must undergo enzyme-mediated activation, a reaction catalyzed by type I nitroreductase (NTR). In the search for new parasitic therapies, we have utilized this finding to investigate whether aziridinyl nitrobenzamide derivatives have activity against bloodstream-form
Trypanosoma brucei
and
Trypanosoma cruzi
amastigotes, parasite stages that replicate in the mammalian host. For
T. cruzi
drug screening, we generated trypanosomes that expressed the luciferase reporter gene and optimized a mammalian infection model in a 96-well plate format. A subset of compounds having a 5-(aziridin-1-yl)-2,4-dinitrobenzyl structure was shown to be metabolized by purified
T. brucei
NTR and when screened against both parasite life cycle stages displayed significant growth-inhibitory properties: the most potent compounds generated 50% inhibitory concentrations of <1 μM. The trypanocidal activity was shown to be NTR specific, since parasites overexpressing this enzyme were hypersensitive to the aziridinyl dinitrobenzyl agents. We conclude that members of the aziridinyl nitrobenzamide class of nitroheterocycles provide new lead structures that have the potential to treat trypanosomal infections.
The impact of tobacco control policies in Albania
Authors: Zaloshnja Eduard , Ross Hana , Levy David T
Published: August 2010

Objective

To assess the impact of a tobacco control law adopted in Albania in 2007 and to estimate the share of illicit cigarettes on the market.

Design

Comparative analysis of two waves of a nationally representative household survey, one conducted before the new law went into effect and the other after 2 years. Official sales data were contrasted with the consumption estimate based on the survey.

Main outcome measures

Smoking prevalence, quit attempts, exposure to cigarette advertising, exposure to second-hand smoke, total cigarette consumption, share of illicit packs among packs possessed by smokers.

Results

Despite the adoption of strong smoke-free policies and adverting restrictions, smoking prevalence in Albania has risen. The increase in prevalence has been driven by higher smoking rates among females (18.9% in 2007 vs 29.3% in 2009) and young adults (23.2% in 2007 vs 38.5% in 2009 among 18–19 year olds). Self-reported exposure to second-hand smoke and cigarette advertising have been reduced since 2007. The majority of respondents are still exposed to second-hand smoke and more than half are exposed to tobacco advertising. Nevertheless, there are signs that the consumption of illicit cigarettes is declining.

Conclusions

The impacts of smoke-free policies and an advertising ban have been limited due to lack of enforcement and failure to adopt a comprehensive set of tobacco control measures. These measures should include sizeable and regular tobacco tax increases in excess of the general level of inflation and income growth. The decline in the share of illicit cigarettes should improve the effectiveness of the cigarette tax policy.
A DOUBLE-MOTION WAVELET AND ITS APPLICATIONS TO ENTERTAINMENT SOUNDS
Authors: TODA HIROSHI , ZHANG ZHONG
Published: August 2010

We have already proposed a new type of wavelet, named the "motion wavelet", whose mother wavelet is varied according to a certain reference signal, and at the same time, transforms another target signal. The wavelet allows variable frequency elements to be picked out from the target signal according to the reference signal. This motion wavelet can also be applied to making entertainment sounds. However, it generates only monaural sound and its effect is simple. In this paper, we propose a new type of motion wavelet having double the modulation performance by the real and imaginary parts of its complex mother wavelet varied according to two different reference signals. Furthermore, we introduce a fast calculation method for it and one of its applications to entertainment sounds.
FEMALE IMMIGRANT ENTREPRENEURSHIP: A DEVELOPING SECTOR IN JAPAN'S ENTREPRENEURIAL ECONOMY
Authors: BILLORE SONIYA , ZAINUDDIN AHMAD HJ , AL-HAJ NORASHFAH HANIM YAAKOP YAHAYA , HALKIAS DAPHNE
Published: August 2010

The role of women in Japan was traditionally restricted to housekeeping and childrearing. Over the years, changes in Japanese lifestyle and attitudes have created new grounds for women to venture into small businesses. Although this new personality aspect of women has been accepted, by and large, in larger cities of Japan, it is yet to be accepted in rural areas. Given this background, it becomes even more challenging for a foreigner — an immigrant woman entrepreneur — to set up shop and conduct business in Japan. This study looks at the status of female immigrant entrepreneurs in Japan. Through a qualitative study, it explores the experiences and challenges female entrepreneurs must face before they achieve stability in their businesses. It highlights and draws attention to areas where changes in governance structure and social acceptance can be made so a more positive environment can be built up and the relationship between Japan and the immigrant entrepreneurs can be strengthened.
Vascular Neurology Nurse Practitioner Provision of Telemedicine Consultations
Authors: Demaerschalk Bart M. , Kiernan Terri-Ellen J. , Investigators STARR
Published: August 2010

Objective. The objective was to define and evaluate a role for the Vascular Neurology-Nurse Practitioner (VN-NP) in the delivery of telemedicine consultations in partnership with a vascular neurologist.Methods. Prospective stroke alert patients at participating hospitals underwent a two-way audio video telemedicine consultation with a VN-NP at a remotely located stroke center in partnership with a vascular neurologist. Demographic information, National Institutes of Health Stroke Scale (NIHSS) scores, diagnoses, CT contraindications to thrombolysis, thrombolysis eligibility, and time interval data were collected. The inter-rater agreement between VN-NP and vascular neurologist assessments was calculated.Results. Ten patients were evaluated. Four were determined to have ischemic stroke, one had a transient ischemic attack, two had intracerebral hemorrhages, and three were stroke mimics. Overall, three patients received thrombolysis. The inter-rater agreement between VN-NP and vascular neurologist assessments were excellent, ranging from 0.9 to 1.0. The duration of VN-NP consultation was53.2±9.0minutes, which included the vascular neurologist supervisory evaluation time of12.0±9.6minutes.Conclusion. This study illustrated that a stroke center VN-NP, in partnership with a vascular neurologist, could deliver timely telemedicine consultations, accurate diagnoses, and correct treatments in acute stroke patients who presented to remotely located rural emergency departments within a hub and spoke network. VN-NPs may fulfill the role of a telestroke provider.
3D Medical Volume Segmentation Using Hybrid Multiresolution Statistical Approaches
Authors: AlZu'bi Shadi , Amira Abbes
Published: August 2010

3D volume segmentation is the process of partitioning voxels into 3D regions (subvolumes) that represent meaningful physical entities which are more meaningful and easier to analyze and usable in future applications. Multiresolution Analysis (MRA) enables the preservation of an image according to certain levels of resolution or blurring. Because of multiresolution quality, wavelets have been deployed in image compression, denoising, and classification. This paper focuses on the implementation of efficient medical volume segmentation techniques. Multiresolution analysis including 3D wavelet and ridgelet has been used for feature extraction which can be modeled using Hidden Markov Models (HMMs) to segment the volume slices. A comparison study has been carried out to evaluate 2D and 3D techniques which reveals
that 3D methodologies can accurately detect the Region Of Interest (ROI). Automatic segmentation has been achieved using HMMs where the ROI is detected accurately but suffers a long computation time for its calculations.
Therapies with Emerging Evidence of Efficacy: Avotermin for the Improvement of Scarring
Authors: Bush Jim , So Karen , Mason Tracey , Occleston Nick L. , O′Kane Sharon , Ferguson Mark W. J.
Published: August 2010

Many patients are dissatisfied with scars on both visible and non‐visible body sites and would value any opportunity to improve or minimise scarring following surgery. Approximately 44 million procedures in the US and 42 million procedures in the EU per annum could benefit from scar reduction therapy. A wide range of non‐invasive and invasive techniques have been used in an attempt to improve scarring although robust, prospective clinical trials to support the efficacy of these therapies are lacking. Differences in wound healing and scar outcome between early fetal and adult wounds led to interest in the role of the TGFβ family of cytokines in scar formation and the identification of TGFβ3 (avotermin) as a potential therapeutic agent for the improvement of scar appearance. Extensive pre‐clinical and human Phase I and II clinical trial programmes have confirmed the scar improving efficacy of avotermin which produces macroscopic and histological improvements in scar architecture, with improved restitution of the epidermis and an organisation of dermal extracellular matrix that more closely resembles normal skin. Avotermin is safe and well tolerated and is currently in Phase III of clinical development, with the first study, in patients undergoing scar revision surgery, fully recruited.
Global Egr1-miRNAs Binding Analysis in PMA-Induced K562 Cells Using ChIP-Seq
Authors: Wang Wei , Zhou Dequang , Shi Xiaolong , Tang Chao , Xie Xueying , Tu Jing , Ge Qinyu , Lu Zuhong
Published: August 2010

Although much is known about microRNAs' regulation in gene expression and their contributions in cell fate, to date, globally lineage-(cell-) specific identification of the binding events between a transcription factor and its targeting microRNA genes is still waiting for elucidation. In this paper, we performed a ChIP-Seq experiment to find the targeting microRNA genes of a transcription factor, Egr1, in human erythroleukemia cell line K562. We found Egr1 binding sites near the promoters of 124 distinct microRNA genes, accounting for about 42% of the miRNAs which have high-confidence predicted promoters (294). We also found EGR1 bind to another 63 pre-miRNAs. We chose 12 of the 187 microRNAs with Egr1 binding sites to perform ChIP-PCR assays and the positive binding signal from ChIP-PCR confirmed the ChIP-Seq results. Our experiments provide the first global binding profile between Egr1 and its targeting microRNA genes in PMA-treated K562 cells, which may facilitate the understanding of pathways controlling microRNA biology in this specific cell line.
Renal Cell Carcinoma Presenting with Cutaneous Metastasis: A Case Report
Authors: Onak Kandemir Nilufer , Barut Figen , Yılmaz Kıvanç , Tokgoz Husnu , Hosnuter Mubin , Ozdamar Sukru Oguz
Published: August 2010

Renal cell carcinoma is the most common kidney tumor in adults. Cutaneous metastasis is a rare first symptom of the disease. This paper describes the diagnosis of a renal cell carcinoma that was indicated by cutaneous metastasis in the head and neck region, and considers the etiopathogenesis of such cases. A careful skin examination is important to detect cutaneous metastasis associated with renal cell carcinomas. Metastatic skin lesions in the head and neck region must be taken into consideration during a differential diagnosis.
Hyperbaric Oxygen Therapy as a Sole Agent Is Not Immunosuppressant in a Highly Immunogenic Mouse Model
Authors: Gassas Adam , Min Weixian , Evans A. Wayne , Carter Susan , Sándor George K. , Grunebaum Eyal
Published: August 2010

Background. Hyperbaric oxygen (HBO) therapy, which is used for many conditions, may also have immunosuppressive effects and could be used for prevention or treatment of graft-versus-host disease (GvHD). If HBO is immunosuppressant, then we hypothesize that HBO therapy will delay the T-cell mediated skin graft rejection. Methods. C57/BL6 black-coated (H2B) mice received skin graft from CBA (H2D) white-coated mice. Mice were treated with either 19 session of 240 kpa oxygen or 29 session of 300 kpa oxygen, for 90 minutes. Mice were housed either 4 per cage or separately, to prevent friction and mechanical factors that may affect graft survival. Skin grafts were assessed daily. Results. There was no difference in length of graft survival between mice that received either regimens of HBO therapy and mice that did not receive HBO therapy. Conclusions. HBO therapy, as a sole agent, did not delay skin graft rejection in a highly immunogenic mouse model.
Burkholderia cepaciaComplex: Emerging Multihost Pathogens Equipped with a Wide Range of Virulence Factors and Determinants
Authors: Sousa Sílvia A. , Ramos Christian G. , Leitão Jorge H.
Published: August 2010

TheBurkholderia cepaciacomplex (Bcc) comprises at least 17 closely-related species of theβ-proteobacteria subdivision, widely distributed in natural and man-made inhabitats. Bcc bacteria are endowed with an extraordinary metabolic diversity and emerged in the 1980s as life-threatening and difficult-to-treat pathogens among patients suffering from cystic fibrosis. More recently, these bacteria became recognized as a threat to hospitalized patients suffering from other diseases, in particular oncological patients. In the present paper, we review these and other traits of Bcc bacteria, as well as some of the strategies used to identify and validate the virulence factors and determinants used by these bacteria. The identification and characterization of these virulence factors is expected to lead to the design of novel therapeutic strategies to fight the infections caused by these emergent multidrug resistant human pathogens.
Significance of Preoperative Evaluations of Tumor Necrosis Factor-Alpha, the Granulocyte/Lymphocyte Ratio and Their Correlation with Regard to Outcome in Gastric Cancer Patients
Authors: Ubukata Hideyuki , Konishi Satoru , Nagata Hiroyuki , Kasuga Nobuhiro , Watanabe Yoshinori , Goto Yoshihisa , Nakada Ichiro , Tabuchi Takafumi
Published: August 2010

Aim: In order to clarify the anti-cancer effects of tumor necrosis factor-α (TNFα), we examined the relationship between the preoperative evaluations of TNFα and the granulocyte/lymphocyte ratio (G/L ratio) in relation to outcome in gastric cancer patients. Materials and Methods: Peripheral blood samples were taken within 1 week before curative gastrectomy for measurement of TNFα and the G/L ratio. Five-year survival was determined in 71 operative gastric cancer cases. Results: The 5-year survival of the high TNFα group (≧8,000 pg/ml ) was 64.1%, 29.0% for the low TNFα group (<8,000 pg/ml) and 13.3 and 73.1% for those of the high (≧4.0) and low (<4.0) G/L ratio groups, respectively. The comparisons of these 5-year survival rates showed statistically significant differences. Moreover, there was a negative linear correlation between TNFα and the G/L ratio regarding outcome. Conclusions: Preoperative evaluations with TNFα and the G/L ratio may be important prognostic indicators, and their correlation may be a good indicator of the degree of effectiveness in activating anti-cancer immunity in gastric cancer patients.
HDAC Inhibition Attenuates Inflammatory, Hypertrophic, and Hypertensive Responses in Spontaneously Hypertensive Rats
Authors: Cardinale Jeffrey P. , Sriramula Srinivas , Pariaut Romain , Guggilam Anuradha , Mariappan Nithya , Elks Carrie M. , Francis Joseph
Published: August 2010

Reactive oxygen species and proinflammatory cytokines contribute to cardiovascular diseases. Inhibition of downstream transcription factors and gene modifiers of these components are key mediators of hypertensive response. Histone acetylases/deacetylases can modulate the gene expression of these hypertrophic and hypertensive components. Therefore, we hypothesized that long-term inhibition of histone deacetylase with valproic acid might attenuate hypertrophic and hypertensive responses by modulating reactive oxygen species and proinflammatory cytokines in SHR rats. Seven-week-old SHR and WKY rats were used in this study. Following baseline blood pressure measurement, rats were administered valproic acid in drinking water (0.71% wt/vol) or vehicle, with pressure measured weekly thereafter. Another set of rats were treated with hydralazine (25 mg/kg per day orally) to determine the pressure-independent effects of HDAC inhibition on hypertension. Following 20 weeks of treatment, heart function was measured using echocardiography, rats were euthanized, and heart tissue was collected for measurement of total reactive oxygen species, as well as proinflammatory cytokine, cardiac hypertrophic, and oxidative stress gene and protein expressions. Blood pressure, proinflammatory cytokines, hypertrophic markers, and reactive oxygen species were increased in SHR versus WKY rats. These changes were decreased in valproic acid-treated SHR rats, whereas hydralazine treatment only reduced blood pressure. These data indicate that long-term histone deacetylase inhibition, independent of the blood pressure response, reduces hypertrophic, proinflammatory, and hypertensive responses by decreasing reactive oxygen species and angiotensin II type1 receptor expression in the heart, demonstrating the importance of uncontrolled histone deacetylase activity in hypertension.
siRNA silencing of PD-L1 and PD-L2 on dendritic cells augments expansion and function of minor histocompatibility antigen–specific CD8+ T cells
Authors: Hobo Willemijn , Maas Frans , Adisty Niken , de Witte Theo , Schaap Nicolaas , van der Voort Robbert , Dolstra Harry
Published: August 2010

Tumor relapse after human leukocyte antigen–matched allogeneic stem cell transplantation (SCT) remains a serious problem, despite the long-term presence of minor histocompatibility antigen (MiHA)–specific memory T cells. Dendritic cell (DC)–based vaccination boosting MiHA-specific T-cell immunity is an appealing strategy to prevent or counteract tumor recurrence, but improvement is necessary to increase the clinical benefit. Here, we investigated whether knockdown of programmed death ligand 1 (PD-L1) and PD-L2 on monocyte-derived DCs results in improved T-cell activation. Electroporation of single siRNA sequences into immature DCs resulted in efficient, specific, and long-lasting knockdown of PD-L1 and PD-L2 expression. PD-L knockdown DCs strongly augmented interferon-γ and interleukin-2 production by stimulated T cells in an allogeneic mixed lymphocyte reaction, whereas no effect was observed on T-cell proliferation. Moreover, we demonstrated that PD-L gene silencing, especially combined PD-L1 and PD-L2 knockdown, resulted in improved proliferation and cytokine production of keyhole limpet hemocyanin–specific CD4+ T cells. Most importantly, PD-L knockdown DCs showed superior potential to expand MiHA-specific CD8+ effector and memory T cells from leukemia patients early after donor lymphocyte infusion and later during relapse. These data demonstrate that PD-L siRNA electroporated DCs are highly effective in enhancing T-cell proliferation and cytokine production, and are therefore attractive cells for improving the efficacy of DC vaccines in cancer patients.
Gene genealogies indicates abundant gene conversions and independent evolutionary histories of the mating-type chromosomes in the evolutionary history of Neurospora tetrasperma
Authors: Menkis Audrius , Whittle Carrie A , Johannesson Hanna
Published: August 2010

Background

The self-fertile filamentous ascomycete Neurospora tetrasperma contains a large (~7 Mbp) and young (< 6 MYA) region of suppressed recombination within its mating-type (mat) chromosomes. The objective of the present study is to reveal the evolutionary history, including key genomic events, associated with the various regions of the mat chromosomes among ten strains representing all the nine known species (lineages) contained within the N. tetrasperma species complex.

Results

Comparative analysis of sequence divergence among alleles of 24 mat-linked genes (mat A and mat a) indicates that a large region of suppressed recombination exists within the mat chromosome for each of nine lineages of N. tetrasperma sensu latu. The recombinationally suppressed region varies in size and gene composition among lineages, and is flanked on both ends by normally recombining regions. Genealogical analyses among lineages reveals that eight gene conversion events have occurred between homologous mat A and mat a-linked alleles of genes located within the region of restricted recombination during the evolutionary history of N. tetrasperma.

Conclusions

We conclude that the region of suppressed recombination in the mat chromosomes has likely been subjected to independent contraction and/or expansion during the evolutionary history of the N. tetrasperma species complex. Furthermore, we infer that gene conversion events are likely a common phenomenon within this recombinationally suppressed genomic region. We argue that gene conversions might provide an efficient mechanism of adaptive editing of functional genes, including the removal of deleterious mutations, within the young recombinationally suppressed region of the mat chromosomes.
A new family of phosphoinositide phosphatases in microorganisms: identification and biochemical analysis
Authors: Beresford Nicola J , Saville Charis , Bennett Hayley J , Roberts Ian S , Tabernero Lydia
Published: August 2010

Background

Phosphoinositide metabolism is essential to membrane dynamics and impinges on many cellular processes, including phagocytosis. Modulation of phosphoinositide metabolism is important for pathogenicity and virulence of many human pathogens, allowing them to survive and replicate in the host cells. Phosphoinositide phosphatases from bacterial pathogens are therefore key players in this modulation and constitute attractive targets for chemotherapy. MptpB, a virulence factor from Mycobacterium tuberculosis, has phosphoinositide phosphatase activity and a distinct active site P-loop signature HCXXGKDR that shares characteristics with eukaryotic lipid phosphatases and protein tyrosine phosphatases. We used this P-loop signature as a "diagnostic motif" to identify related putative phosphatases with phosphoinositide activity in other organisms.

Results

We found more than 200 uncharacterised putative phosphatase sequences with the conserved signature in bacteria, with some related examples in fungi and protozoa. Many of the sequences identified belong to recognised human pathogens. Interestingly, no homologues were found in any other organisms including Archaea, plants, or animals. Phylogenetic analysis revealed that these proteins are unrelated to classic eukaryotic lipid phosphatases. However, biochemical characterisation of those from Listeria monocytogenes and Leishmania major, demonstrated that, like MptpB, they have phosphatase activity towards phosphoinositides. Mutagenesis studies established that the conserved Asp and Lys in the P-loop signature (HCXXGKD R) are important in catalysis and substrate binding respectively. Furthermore, we provide experimental evidence that the number of basic residues in the P-loop is critical in determining activity towards poly-phosphoinositides.

Conclusion

This new family of enzymes in microorganisms shows distinct sequence and biochemical characteristics to classic eukaryotic lipid phosphatases and they have no homologues in humans. This study provides a foundation for examining the biological role of this new family of phosphatases and their potential as pharmaceutical targets against infectious diseases.
Dynamics of dendritic cell maturation are identified through a novel filtering strategy applied to biological time-course microarray replicates
Authors: Olex Amy L , Hiltbold Elizabeth M , Leng Xiaoyan , Fetrow Jacquelyn S
Published: August 2010

Background

Dendritic cells (DC) play a central role in primary immune responses and become potent stimulators of the adaptive immune response after undergoing the critical process of maturation. Understanding the dynamics of DC maturation would provide key insights into this important process. Time course microarray experiments can provide unique insights into DC maturation dynamics. Replicate experiments are necessary to address the issues of experimental and biological variability. Statistical methods and averaging are often used to identify significant signals. Here a novel strategy for filtering of replicate time course microarray data, which identifies consistent signals between the replicates, is presented and applied to a DC time course microarray experiment.

Results

The temporal dynamics of DC maturation were studied by stimulating DC with poly(I:C) and following gene expression at 5 time points from 1 to 24 hours. The novel filtering strategy uses standard statistical and fold change techniques, along with the consistency of replicate temporal profiles, to identify those differentially expressed genes that were consistent in two biological replicate experiments. To address the issue of cluster reproducibility a consensus clustering method, which identifies clusters of genes whose expression varies consistently between replicates, was also developed and applied. Analysis of the resulting clusters revealed many known and novel characteristics of DC maturation, such as the up-regulation of specific immune response pathways. Intriguingly, more genes were down-regulated than up-regulated. Results identify a more comprehensive program of down-regulation, including many genes involved in protein synthesis, metabolism, and housekeeping needed for maintenance of cellular integrity and metabolism.

Conclusions

The new filtering strategy emphasizes the importance of consistent and reproducible results when analyzing microarray data and utilizes consistency between replicate experiments as a criterion in both feature selection and clustering, without averaging or otherwise combining replicate data. Observation of a significant down-regulation program during DC maturation indicates that DC are preparing for cell death and provides a path to better understand the process. This new filtering strategy can be adapted for use in analyzing other large-scale time course data sets with replicates.
Voltage dependent anion channel-1 regulates death receptor mediated apoptosis by enabling cleavage of caspase-8
Authors: Chacko Alex D , Liberante Fabio , Paul Ian , Longley Daniel B , Fennell Dean A
Published: August 2010

Background

Activation of the extrinsic apoptosis pathway by tumour necrosis factor related apoptosis inducing ligand (TRAIL) is a novel therapeutic strategy for treating cancer that is currently under clinical evaluation. Identification of molecular biomarkers of resistance is likely to play an important role in predicting clinical anti tumour activity. The involvement of the mitochondrial type 1 voltage dependent anion channel (VDAC1) in regulating apoptosis has been highly debated. To date, a functional role in regulating the extrinsic apoptosis pathway has not been formally excluded.

Methods

We carried out stable and transient RNAi knockdowns of VDAC1 in non-small cell lung cancer cells, and stimulated the extrinsic apoptotic pathway principally by incubating cells with the death ligand TRAIL. We used in-vitro apoptotic and cell viability assays, as well as western blot for markers of apoptosis, to demonstrate that TRAIL-induced toxicity is VDAC1 dependant. Confocal microscopy and mitochondrial fractionation were used to determine the importance of mitochondria for caspase-8 activation.

Results

Here we show that either stable or transient knockdown of VDAC1 is sufficient to antagonize TRAIL mediated apoptosis in non-small cell lung cancer (NSCLC) cells. Specifically, VDAC1 is required for processing of procaspase-8 to its fully active p18 form at the mitochondria. Loss of VDAC1 does not alter mitochondrial sensitivity to exogenous caspase-8-cleaved BID induced mitochondrial depolarization, even though VDAC1 expression is essential for TRAIL dependent activation of the intrinsic apoptosis pathway. Furthermore, expression of exogenous VDAC1 restores the apoptotic response to TRAIL in cells in which endogenous VDAC1 has been selectively silenced.

Conclusions

Expression of VDAC1 is required for full processing and activation of caspase-8 and supports a role for mitochondria in regulating apoptosis signaling via the death receptor pathway.
Non-uniform recovery of left ventricular transmural mechanics in ST-segment elevation myocardial infarction
Authors: Caracciolo Giuseppe , Eleid Mackram F , Abe Haruhiko , Bhatia Nisha , Fortuin F David , Wilansky Susan , Carerj Scipione , Sengupta Partho P
Published: August 2010

Background

After a transient ischemic episode, the subendocardial region is more severely injured than outer subepicardial layers and may regain a proportionately greater degree of mechanical function in the longitudinal direction. We sought to explore left ventricular (LV) transmural mechanics in patients with ST-segment elevation myocardial infarction (STEMI) for determining the mechanism underlying recovery of global LV function after primary percutaneous coronary intervention (PCI).

Methods

A total of 42 patients (62 ± 11 years old, 71% male) with a first STEMI underwent serial assessments of LV longitudinal, circumferential and radial strains (LS, CS and RS) by selective tracking of subendocardial and subepicardial regions within 48 hours and a median of 5 months after PCI. LV mechanical parameters were compared with sixteen age and gender matched normal controls.

Results

In comparison with controls, endocardial and epicardial LS were markedly attenuated at 48 hours following PCI (P < 0.001). An improvement in LV ejection fraction (EF > 5%) following PCI was seen in 24 (57%) patients and was associated with improvement in endocardial and epicardial LS (P < 0.001 and P = 0.003, respectively) and endocardial CS (P = 0.01). Radial strain and wall motion score index, however, remained persistently abnormal. The change in endocardial LS (OR 1.2, 95% CI 1.03 to 1.42, P = 0.01) and the change in epicardial LS (OR 1.2, 95% 1.03 to 1.46, P = 0.02) were significantly associated with the improvement in LVEF, independent of the location of STEMI and the presence of underlying multivessel disease.

Conclusions

In patients with STEMI treated by PCI, the recovery of LV subendocardial shortening strain seen in the longitudinal direction underlies the improvement in LV global function despite persistent abnormalities in radial mechanics and wall motion score index.