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Sample records for clinical dna histogram

  1. Theory and Application of DNA Histogram Analysis.

    ERIC Educational Resources Information Center

    Bagwell, Charles Bruce

    The underlying principles and assumptions associated with DNA histograms are discussed along with the characteristics of fluorescent probes. Information theory was described and used to calculate the information content of a DNA histogram. Two major types of DNA histogram analyses are proposed: parametric and nonparametric analysis. Three levels…

  2. High-fidelity DNA histograms in neoplastic progression in Barrett's esophagus.

    PubMed

    Yu, Chenggong; Zhang, Xiaoqi; Huang, Qin; Klein, Michael; Goyal, Raj K

    2007-05-01

    This study describes the high-fidelity DNA histograms in different stages of neoplastic progression to Barrett's adenocarcinoma (BAC). High-fidelity DNA histograms were obtained with image cytometry on sections, and were classified based on DNA index values of the peaks into diploid, mild aneuploid, moderate aneuploid and severe aneuploid. Heterogeneity index (HI) representing cells with different DNA content and the 5N exceeding cell fraction were determined. One hundred and eighty-seven cases, including 34 normal gastrointestinal mucosa (control), 66 Barrett's-specialized intestinal metaplasia (SIM), 22 low-grade dysplasia (LGD), 22 high-grade dysplasia (HGD) and 43 BAC were investigated. Controls showed sharp diploid peaks with HI values less than 13, and no 5N exceeding nuclei. SIM showed a spectrum of histograms including diploid, mild aneuploid and moderate aneuploid histograms. The frequency and severity of aneuploidy increased with worsening histological grades of dysplasia. All BAC cases were aneuploid, with moderate or severe aneuploidy. Marked elevated HI values (>20) and 5N exceeding fractions (>5%) were found in 5%, 32%, 50% and 88% of cases with SIM, LGD, HGD and BAC, respectively. The high-fidelity DNA histograms suggest that (1) Barrett's SIM may already be dysplastic in nature, and all BAC may be markedly aneuploid; and (2) elevated cellular DNA heterogeneity and 5N fractions may be markers of progressive chromosomal changes and 'unstable aneuploidy' that identifies progressive lesions. PMID:17310216

  3. A rule-based expert system for the automatic classification of DNA "ploidy" histograms measured by the CAS 200 image analysis system.

    PubMed

    Marchevsky, A M; Truong, H; Tolmachoff, T

    1997-02-15

    DNA "ploidy" histogram interpretation is one of the most important sources of variation in DNA image cytometry and is influenced by multiple technical factors such as scaling, selection of peaks, and variable classification criteria. A rule-based expert system was developed to automate and eliminate subjectivity from this interpretative process. Ninety-eight Feulgen stained histologic sections from patients with breast, colon, and lung cancer were measured with the CAS 200 image analysis system (Becton Dickinson, Santa Clara, CA); they included diploid (n = 42), aneuploid (n = 46), tetraploid (n = 7), and multiploid (n = 3) examples. The data was converted from listmode format into ASCII with the aid of CELLSHEET software (JVC Imaging, Elmhurst, IL). Individual microphotometric nuclear measurements were sorted to one of 64 bins based on DNA index. The 64 bins were then divided into 5 semi-arbitrarily defined ranges: hypodiploid, diploid, aneuploid, tetraploid, and hypertetraploid. The nuclear percentages in each range were calculated with EXCEL 4.0 (Microsoft, Redmond, WA). The histograms were divided into 2 equal sets: training and testing. The data from the training set were used to develop 16 IF-THEN rules to classify the histograms into diploid, aneuploid, or tetraploid. A macro was programmed in EXCEL to automate all these operations. The rule-based expert system classified correctly 45/50 histograms of the training set. Two tetraploid histograms were classified as aneuploid. Three multiploid histograms were classified as tetraploid. All histograms in the testing set were correctly classified by the expert system. The potential role of rule-based expert system technology for the objective classification of DNA "ploidy" histograms measured by image cytometry is discussed. PMID:9056741

  4. Identification of column edges of DNA fragments by using K-means clustering and mean algorithm on lane histograms of DNA agarose gel electrophoresis images

    NASA Astrophysics Data System (ADS)

    Turan, Muhammed K.; Sehirli, Eftal; Elen, Abdullah; Karas, Ismail R.

    2015-07-01

    Gel electrophoresis (GE) is one of the most used method to separate DNA, RNA, protein molecules according to size, weight and quantity parameters in many areas such as genetics, molecular biology, biochemistry, microbiology. The main way to separate each molecule is to find borders of each molecule fragment. This paper presents a software application that show columns edges of DNA fragments in 3 steps. In the first step the application obtains lane histograms of agarose gel electrophoresis images by doing projection based on x-axis. In the second step, it utilizes k-means clustering algorithm to classify point values of lane histogram such as left side values, right side values and undesired values. In the third step, column edges of DNA fragments is shown by using mean algorithm and mathematical processes to separate DNA fragments from the background in a fully automated way. In addition to this, the application presents locations of DNA fragments and how many DNA fragments exist on images captured by a scientific camera.

  5. Interlaboratory reproducibility of semiautomated cell cycle analysis of flow cytometry DNA-histograms obtained from fresh material of 1,295 breast cancer cases.

    PubMed

    Bergers, E; Montironi, R; van Diest, P J; Prete, E; Baak, J P

    1996-06-01

    Conflicting prognostic results have been published as to the DNA variables, such as DNA ploidy, DNA index, and % S-phase cells for breast cancer patients. These variables can be obtained by interpreting DNA histograms by cell cycle analysis. Explanations for these conflicting results might be found on the level of the interpretation of the DNA histograms. In a previous study, the semi automated cell cycle analysis computer program MultiCycle (Phoenix Flow Systems, San Diego, CA) showed high intralaboratory reproducibility. However, what types of DNA histograms may cause disagreements was still unclear. The aim of this study was to determine the interlaboratory reproducibility of MultiCycle-based cell cycle analysis of 1,295 flow cytometric DNA histograms derived from fresh frozen breast cancer material and to clarify potential sources of interobserver variation when analyzing DNA histograms. DNA ploidy classification into diploid, hyperdiploid, tetraploid, hypertetraploid, and multiploid showed an interlaboratory agreement of 94% (kappa value = 0.92). The 6% discrepancies (n = 74) were caused by tetraploid peaks, as established in one laboratory, which shifted outside the tetraploid region on reanalysis by the other laboratory (37%), shoulders sometimes interpreted as peaks (24%), small peaks not always recognized as such (24%), fitting failures (10%), and overlooking of tetraploid peaks (5%). Furthermore, the cell cycle analysis variables showed variable reproducibility. The % S-phase cells of the first, second, and third cell cycle showed overall a moderate reproducibility (0.62 < or = R < or = 0.79), but the average % S-phase cells and the average aneuploid % S-phase cells were more reproducible with correlation coefficients of 0.89 and 0.81, respectively. The coefficient of variation of the G0/G1 peak of the first cell cycle, the DNA indices and the % diploid cells were highly reproducible (R > or = 0.94), and the % G2/M-phase cells of the first, second, and

  6. Clinical implementation of dose-volume histogram predictions for organs-at-risk in IMRT planning

    NASA Astrophysics Data System (ADS)

    Moore, K. L.; Appenzoller, L. M.; Tan, J.; Michalski, J. M.; Thorstad, W. L.; Mutic, S.

    2014-03-01

    True quality control (QC) of the planning process requires quantitative assessments of treatment plan quality itself, and QC in IMRT has been stymied by intra-patient anatomical variability and inherently complex three-dimensional dose distributions. In this work we describe the development of an automated system to reduce clinical IMRT planning variability and improve plan quality using mathematical models that predict achievable OAR DVHs based on individual patient anatomy. These models rely on the correlation of expected dose to the minimum distance from a voxel to the PTV surface, whereby a three-parameter probability distribution function (PDF) was used to model iso-distance OAR subvolume dose distributions. DVH models were obtained by fitting the evolution of the PDF with distance. Initial validation on clinical cohorts of 40 prostate and 24 head-and-neck plans demonstrated highly accurate model-based predictions for achievable DVHs in rectum, bladder, and parotid glands. By quantifying the integrated difference between candidate DVHs and predicted DVHs, the models correctly identified plans with under-spared OARs, validated by replanning all cases and correlating any realized improvements against the predicted gains. Clinical implementation of these predictive models was demonstrated in the PINNACLE treatment planning system by use of existing margin expansion utilities and the scripting functionality inherent to the system. To maintain independence from specific planning software, a system was developed in MATLAB to directly process DICOM-RT data. Both model training and patient-specific analyses were demonstrated with significant computational accelerations from parallelization.

  7. Dose-Volume Histogram Parameters and Clinical Factors Associated With Pleural Effusion After Chemoradiotherapy in Esophageal Cancer Patients

    SciTech Connect

    Shirai, Katsuyuki; Tamaki, Yoshio; Kitamoto, Yoshizumi; Murata, Kazutoshi; Satoh, Yumi; Higuchi, Keiko; Nonaka, Tetsuo; Ishikawa, Hitoshi; Katoh, Hiroyuki; Takahashi, Takeo; Nakano, Takashi

    2011-07-15

    Purpose: To investigate the dose-volume histogram parameters and clinical factors as predictors of pleural effusion in esophageal cancer patients treated with concurrent chemoradiotherapy (CRT). Methods and Materials: Forty-three esophageal cancer patients treated with definitive CRT from January 2001 to March 2007 were reviewed retrospectively on the basis of the following criteria: pathologically confirmed esophageal cancer, available computed tomography scan for treatment planning, 6-month follow-up after CRT, and radiation dose {>=}50 Gy. Exclusion criteria were lung metastasis, malignant pleural effusion, and surgery. Mean heart dose, mean total lung dose, and percentages of heart or total lung volume receiving {>=}10-60 Gy (Heart-V{sub 10} to V{sub 60} and Lung-V{sub 10} to V{sub 60}, respectively) were analyzed in relation to pleural effusion. Results: The median follow-up time was 26.9 months (range, 6.7-70.2) after CRT. Of the 43 patients, 15 (35%) developed pleural effusion. By univariate analysis, mean heart dose, Heart-V{sub 10} to V{sub 60}, and Lung-V{sub 50} to V{sub 60} were significantly associated with pleural effusion. Poor performance status, primary tumor of the distal esophagus, and age {>=}65 years were significantly related with pleural effusion. Multivariate analysis identified Heart-V{sub 50} as the strongest predictive factor for pleural effusion (p = 0.01). Patients with Heart-V{sub 50} <20%, 20%{<=} Heart-V{sub 50} <40%, and Heart-V{sub 50} {>=}40% had 6%, 44%, and 64% of pleural effusion, respectively (p < 0.01). Conclusion: Heart-V{sub 50} is a useful parameter for assessing the risk of pleural effusion and should be reduced to avoid pleural effusion.

  8. Does DNA cytometry have a place in the clinical laboratory

    SciTech Connect

    Mayall, B. ); Waldman, F.; Chew, K.; Christov, K.; Goodson, W.; Ljung, B.M. . Lab. for Cell Analysis); Smith, H.S. )

    1990-01-24

    We are investigating the potential utility of cellular markers, including cellular proliferation and DNA cytometry, as independent diagnostic and prognostic markers in human breast cancer. However, as the clinical laboratory is responsible for providing physicians with data relevant to the patient, it is essential first to establish the validity of such markers before their use is recommended. Prospective validation is time-consuming and costly for tests of human malignancies, such as breast cancer, which may follow a lengthy and indolent course requiring patients to be followed for a decade or more before their clinical outcome is known. Therefore, retrospective studies on archival material are used whenever possible. Cell proliferation is recognized as an important diagnostic and prognostic marker for human breast cancer and a tritiated thymidine DNA labeling index greater than 5% is associated with a markedly less favorable outcome. Incorporation of bromodeoxyuridine (BrdUrd) into the DNA of S phase cells gives a similar labeling index. Unfortunately, paraffin-embedded archival material is rarely pre-labeled, and so DNA cytometry of either whole nuclei disaggregated from thick sections or partial nuclei in thin sections must be used as an indirect approach to estimate cellular proliferative activity. We are particularly interested in validating the DNA cytometry of thin sections and in relating the DNA histogram to in vivo BrdUrd labeling index, which is our standard for cellular proliferation. 6 refs., 1 fig.

  9. Histograms and Frequency Density.

    ERIC Educational Resources Information Center

    Micromath, 2003

    2003-01-01

    Introduces exercises on histograms and frequency density. Guides pupils to Discovering Important Statistical Concepts Using Spreadsheets (DISCUSS), created at the University of Coventry. Includes curriculum points, teaching tips, activities, and internet address (http://www.coventry.ac.uk/discuss/). (KHR)

  10. Histograms and Raisin Bread

    ERIC Educational Resources Information Center

    Leyden, Michael B.

    1975-01-01

    Describes various elementary school activities using a loaf of raisin bread to promote inquiry skills. Activities include estimating the number of raisins in the loaf by constructing histograms of the number of raisins in a slice. (MLH)

  11. Structure Size Enhanced Histogram

    NASA Astrophysics Data System (ADS)

    Wesarg, Stefan; Kirschner, Matthias

    Direct volume visualization requires the definition of transfer functions (TFs) for the assignment of opacity and color. Multi-dimensional TFs are based on at least two image properties, and are specified by means of 2D histograms. In this work we propose a new type of a 2D histogram which combines gray value with information about the size of the structures. This structure size enhanced (SSE) histogram is an intuitive approach for representing anatomical features. Clinicians — the users we are focusing on — are much more familiar with selecting features by their size than by their gradient magnitude value. As a proof of concept, we employ the SSE histogram for the definition of two-dimensional TFs for the visualization of 3D MRI and CT image data.

  12. Fast tracking using edge histograms

    NASA Astrophysics Data System (ADS)

    Rokita, Przemyslaw

    1997-04-01

    This paper proposes a new algorithm for tracking objects and objects boundaries. This algorithm was developed and applied in a system used for compositing computer generated images and real world video sequences, but can be applied in general in all tracking systems where accuracy and high processing speed are required. The algorithm is based on analysis of histograms obtained by summing along chosen axles pixels of edge segmented images. Edge segmentation is done by spatial convolution using gradient operator. The advantage of such an approach is that it can be performed in real-time using available on the market hardware convolution filters. After edge extraction and histograms computation, respective positions of maximums in edge intensity histograms, in current and previous frame, are compared and matched. Obtained this way information about displacement of histograms maximums, can be directly converted into information about changes of target boundaries positions along chosen axles.

  13. CHIL - a comprehensive histogramming language

    SciTech Connect

    Milner, W.T.; Biggerstaff, J.A.

    1984-01-01

    A high level language, CHIL, has been developed for use in processing event-by-event experimental data at the Holifield Heavy Ion Research Facility (HHIRF) using PERKIN-ELMER 3230 computers. CHIL has been fully integrated into all software which supports on-line and off-line histogramming and off-line preprocessing. CHIL supports simple gates, free-form-gates (2-D regions of arbitrary shape), condition test and branch statements, bit-tests, loops, calls to up to three user supplied subroutines and histogram generating statements. Any combination of 1, 2, 3 or 4-D histograms (32 megachannels max) may be recorded at 16 or 32 bits/channel. User routines may intercept the data being processed and modify it as desired. The CPU-intensive part of the processing utilizes microcoded routines which enhance performance by about a factor of two.

  14. Rapid extraction of DNA from archival clinical specimens: our experiences.

    PubMed

    Poljak, M; Seme, K; Gale, N

    2000-01-01

    The analysis of DNA extracted from archival clinical specimens using polymerase chain reaction represents the basis of a variety of research and diagnostic protocols in medicine. However, the selection of optimal DNA extraction method is critical if such an analysis is to be successful. Recently, we have evaluated a number of rapid DNA extraction protocols in order to find the most suitable method for routine processing of the most common archival materials in pathological and cytological laboratories: paraffin-embedded tissues and Papanicolaou- or Giemsa-stained smears. Our results demonstrate that rapid DNA extraction methods have comparable DNA extraction efficiencies with standard DNA isolation protocols on archival clinical specimens with the exception of Giemsa-stained smears. PMID:10653137

  15. Clinical significance of circulating plasma DNA in gastric cancer.

    PubMed

    Fang, Wen-Liang; Lan, Yuan-Tzu; Huang, Kuo-Hung; Liu, Chien-An; Hung, Yi-Ping; Lin, Chien-Hsing; Jhang, Fang-Yu; Chang, Shih-Ching; Chen, Ming-Huang; Chao, Yee; Lin, Wen-Chang; Lo, Su-Shun; Fen-Yau Li, Anna; Wu, Chew-Wun; Chiou, Shih-Hwa; Shyr, Yi-Ming

    2016-06-15

    With the progression of molecular techniques, the detection of circulating plasma DNA (cpDNA) is clinically feasible. However, the role of the cpDNA levels in gastric cancer is not well understood. This study assessed the mutational profile in primary tumors and clarified the clinical utility of quantitative and qualitative cpDNA alterations in 277 patients with advanced gastric cancer. The concentrations of cpDNA were measured by TaqMan qPCR, and 68 mutations in 8 genes were studied for cpDNA mutations. The median cpDNA concentrations in patients with stages I, II, and III gastric cancer were 3979, 3390 and 4278 copies/mL, respectively, and increased to 11,380 copies/mL in patients with Stage IV gastric cancer (p < 0.001). Among the 35 patients harboring cpDNA mutations, Stage IV patients (100%) were more likely to display high cpDNA levels than were Stage I (33.3%), II (75%) and III patients (66.7%) (p = 0.037). Patients displaying high cpDNA levels were more likely to experience peritoneal recurrence and exhibited significantly lower 5-year overall survival rates (39.2% vs. 45.8%, p = 0.039) than did patients displaying low cpDNA levels. Only for late stage (Stages III or IV) gastric cancer, patients harboring cpDNA mutations were more likely to experience vascular invasion (20% vs. 2.4%, p = 0.036) and exhibited a lower 5-year overall survival rate than did those lacking cpDNA mutations (5.6% vs. 31.5%, p = 0.028). High cpDNA levels are associated with peritoneal recurrence and poor prognosis in patients with advanced gastric cancer; harboring cpDNA mutations is associated with poor prognosis among patients with late stage gastric cancer. PMID:26815009

  16. An Improved Model for Predicting Radiation Pneumonitis Incorporating Clinical and Dosimetric Variables;Lung cancer; Radiation pneumonitis; Dose-volume histogram; Angiotensin converting enzyme inhibitor

    SciTech Connect

    Jenkins, Peter; Watts, Joanne

    2011-07-15

    Purpose: Single dose-volume metrics are of limited value for the prediction of radiation pneumonitis (RP) in day-to-day clinical practice. We investigated whether multiparametric models that incorporate clinical and physiologic factors might have improved accuracy. Methods and Materials: The records of 160 patients who received radiation therapy for non-small-cell lung cancer were reviewed. All patients were treated to the same dose and with an identical technique. Dosimetric, pulmonary function, and clinical parameters were analyzed to determine their ability to predict for the subsequent development of RP. Results: Twenty-seven patients (17%) developed RP. On univariate analysis, the following factors were significantly correlated with the risk of pneumonitis: fractional volume of lung receiving >5-20 Gy, absolute volume of lung spared from receiving >5-15 Gy, mean lung dose, craniocaudal position of the isocenter, transfer coefficient for carbon monoxide (KCOc), total lung capacity, coadministration of angiotensin converting enzyme inhibitors, and coadministration of angiotensin receptor antagonists. By combining the absolute volume of lung spared from receiving >5 Gy with the KCOc, we defined a new parameter termed Transfer Factor Spared from receiving >5 Gy (TFS{sub 5}). The area under the receiver operator characteristic curve for TFS{sub 5} was 0.778, increasing to 0.846 if patients receiving modulators of the renin-angiotensin system were excluded from the analysis. Patients with a TFS{sub 5} <2.17 mmol/min/kPa had a risk of RP of 30% compared with 5% for the group with a TFS{sub 5} {>=}2.17. Conclusions: TFS{sub 5} represents a simple parameter that can be used in routine clinical practice to more accurately segregate patients into high- and low-risk groups for developing RP.

  17. Transposon leads to contamination of clinical pDNA vaccine.

    PubMed

    van der Heijden, I; Gomez-Eerland, R; van den Berg, J H; Oosterhuis, K; Schumacher, T N; Haanen, J B A G; Beijnen, J H; Nuijen, B

    2013-07-11

    We report an unexpected contamination during clinical manufacture of a Human Papilomavirus (HPV) 16 E6 encoding plasmid DNA (pDNA) vaccine, with a transposon originating from the Escherichia coli DH5 host cell genome. During processing, presence of this transposable element, insertion sequence 2 (IS2) in the plasmid vector was not noticed until quality control of the bulk pDNA vaccine when results of restriction digestion, sequencing, and CGE analysis were clearly indicative for the presence of a contaminant. Due to the very low level of contamination, only an insert-specific PCR method was capable of tracing back the presence of the transposon in the source pDNA and master cell bank (MCB). Based on the presence of an uncontrolled contamination with unknown clinical relevance, the product was rejected for clinical use. In order to prevent costly rejection of clinical material, both in-process controls and quality control methods must be sensitive enough to detect such a contamination as early as possible, i.e. preferably during plasmid DNA source generation, MCB production and ultimately during upstream processing. However, as we have shown that contamination early in the process development pipeline (source pDNA, MCB) can be present below limits of detection of generally applied analytical methods, the introduction of "engineered" or transposon-free host cells seems the only 100% effective solution to avoid contamination with movable elements and should be considered when searching for a suitable host cell-vector combination. PMID:23707695

  18. Quantification of emphysema severity by histogram analysis of CT scans.

    PubMed

    Mendonça, Paulo R S; Padfield, Dirk R; Ross, James C; Miller, James V; Dutta, Sandeep; Gautham, Sardar Mal

    2005-01-01

    Emphysema is characterized by the destruction and over distension of lung tissue, which manifest on high resolution computer tomography (CT) images as regions of low attenuation. Typically, it is diagnosed by clinical symptoms, physical examination, pulmonary function tests, and X-ray and CT imaging. In this paper we discuss a quantitative imaging approach to analyze emphysema which employs low-level segmentations of CT images that partition the data into perceptually relevant regions. We constructed multi-dimensional histograms of feature values computed over the image segmentation. For each region in the segmentation, we derive a rich set of feature measurements. While we can use any combination of physical and geometric features, we found that limiting the scope to two features - the mean attenuation across a region and the region area - is effective. The subject histogram is compared to a set of canonical histograms representative of various stages of emphysema using the Earth Mover's Distance metric. Disease severity is assigned based on which canonical histogram is most similar to the subject histogram. Experimental results with 81 cases of emphysema at different stages of disease progression show good agreement against the reading of an expert radiologist. PMID:16685912

  19. DNA Damage in Chronic Kidney Disease: Evaluation of Clinical Biomarkers

    PubMed Central

    Schupp, Nicole; Stopper, Helga; Heidland, August

    2016-01-01

    Patients with chronic kidney disease (CKD) exhibit an increased cancer risk compared to a healthy control population. To be able to estimate the cancer risk of the patients and to assess the impact of interventional therapies thereon, it is of particular interest to measure the patients' burden of genomic damage. Chromosomal abnormalities, reduced DNA repair, and DNA lesions were found indeed in cells of patients with CKD. Biomarkers for DNA damage measurable in easily accessible cells like peripheral blood lymphocytes are chromosomal aberrations, structural DNA lesions, and oxidatively modified DNA bases. In this review the most common methods quantifying the three parameters mentioned above, the cytokinesis-block micronucleus assay, the comet assay, and the quantification of 8-oxo-7,8-dihydro-2′-deoxyguanosine, are evaluated concerning the feasibility of the analysis and regarding the marker's potential to predict clinical outcomes. PMID:27313827

  20. Quantitative histogram analysis of images

    NASA Astrophysics Data System (ADS)

    Holub, Oliver; Ferreira, Sérgio T.

    2006-11-01

    A routine for histogram analysis of images has been written in the object-oriented, graphical development environment LabVIEW. The program converts an RGB bitmap image into an intensity-linear greyscale image according to selectable conversion coefficients. This greyscale image is subsequently analysed by plots of the intensity histogram and probability distribution of brightness, and by calculation of various parameters, including average brightness, standard deviation, variance, minimal and maximal brightness, mode, skewness and kurtosis of the histogram and the median of the probability distribution. The program allows interactive selection of specific regions of interest (ROI) in the image and definition of lower and upper threshold levels (e.g., to permit the removal of a constant background signal). The results of the analysis of multiple images can be conveniently saved and exported for plotting in other programs, which allows fast analysis of relatively large sets of image data. The program file accompanies this manuscript together with a detailed description of two application examples: The analysis of fluorescence microscopy images, specifically of tau-immunofluorescence in primary cultures of rat cortical and hippocampal neurons, and the quantification of protein bands by Western-blot. The possibilities and limitations of this kind of analysis are discussed. Program summaryTitle of program: HAWGC Catalogue identifier: ADXG_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/ADXG_v1_0 Program obtainable from: CPC Program Library, Queen's University of Belfast, N. Ireland Computers: Mobile Intel Pentium III, AMD Duron Installations: No installation necessary—Executable file together with necessary files for LabVIEW Run-time engine Operating systems or monitors under which the program has been tested: WindowsME/2000/XP Programming language used: LabVIEW 7.0 Memory required to execute with typical data:˜16MB for starting and ˜160MB used for

  1. Spline smoothing of histograms by linear programming

    NASA Technical Reports Server (NTRS)

    Bennett, J. O.

    1972-01-01

    An algorithm for an approximating function to the frequency distribution is obtained from a sample of size n. To obtain the approximating function a histogram is made from the data. Next, Euclidean space approximations to the graph of the histogram using central B-splines as basis elements are obtained by linear programming. The approximating function has area one and is nonnegative.

  2. Combining Vector Quantization and Histogram Equalization.

    ERIC Educational Resources Information Center

    Cosman, Pamela C.; And Others

    1992-01-01

    Discussion of contrast enhancement techniques focuses on the use of histogram equalization with a data compression technique, i.e., tree-structured vector quantization. The enhancement technique of intensity windowing is described, and the use of enhancement techniques for medical images is explained, including adaptive histogram equalization.…

  3. Interpreting Histograms. As Easy as It Seems?

    ERIC Educational Resources Information Center

    Lem, Stephanie; Onghena, Patrick; Verschaffel, Lieven; Van Dooren, Wim

    2014-01-01

    Histograms are widely used, but recent studies have shown that they are not as easy to interpret as it might seem. In this article, we report on three studies on the interpretation of histograms in which we investigated, namely, (1) whether the misinterpretation by university students can be considered to be the result of heuristic reasoning, (2)…

  4. Pilot study in the treatment of endometrial carcinoma with 3D image-based high-dose-rate brachytherapy using modified Heyman packing: Clinical experience and dose-volume histogram analysis

    SciTech Connect

    Weitmann, Hajo Dirk . E-mail: dirk.weitmann@akhwien.at; Poetter, Richard; Waldhaeusl, Claudia; Nechvile, Elisabeth; Kirisits, Christian; Knocke, Tomas Hendrik

    2005-06-01

    Purpose: The aim of this study was to evaluate dose distribution within uterus (clinical target volume [CTV]) and tumor (gross tumor volume [GTV]) and the resulting clinical outcome based on systematic three-dimensional treatment planning with dose-volume adaptation. Dose-volume assessment and adaptation in organs at risk and its impact on side effects were investigated in parallel. Methods and Materials: Sixteen patients with either locally confined endometrial carcinoma (n = 15) or adenocarcinoma of uterus and ovaries after bilateral salpingo-oophorectomy (n = 1) were included. Heyman packing was performed with mean 11 Norman-Simon applicators (3-18). Three-dimensional treatment planning based on computed tomography (n = 29) or magnetic resonance imaging (n = 18) was done in all patients with contouring of CTV, GTV, and organs at risk. Dose-volume adaptation was achieved by dwell location and time variation (intensity modulation). Twelve patients treated with curative intent received five to seven fractions of high-dose-rate brachytherapy (7 Gy per fraction) corresponding to a total dose of 60 Gy (2 Gy per fraction and {alpha}/{beta} of 10 Gy) to the CTV. Four patients had additional external beam radiotherapy (range, 10-40 Gy). One patient had salvage brachytherapy and 3 patients were treated with palliative intent. A dose-volume histogram analysis was performed in all patients. On average, 68% of the CTV and 92% of the GTV were encompassed by the 60 Gy reference volume. Median minimum dose to 90% of CTV and GTV (D90) was 35.3 Gy and 74 Gy, respectively. Results: All patients treated with curative intent had complete remission (12/12). After a median follow-up of 47 months, 5 patients are alive without tumor. Seven patients died without tumor from intercurrent disease after median 22 months. The patient with salvage treatment had a second local recurrence after 27 months and died of endometrial carcinoma after 57 months. In patients treated with palliative

  5. DNA repair mechanisms and their clinical impact in glioblastoma.

    PubMed

    Erasimus, Hélène; Gobin, Matthieu; Niclou, Simone; Van Dyck, Eric

    2016-01-01

    Despite surgical resection and genotoxic treatment with ionizing radiation and the DNA alkylating agent temozolomide, glioblastoma remains one of the most lethal cancers, due in great part to the action of DNA repair mechanisms that drive resistance and tumor relapse. Understanding the molecular details of these mechanisms and identifying potential pharmacological targets have emerged as vital tasks to improve treatment. In this review, we introduce the various cellular systems and animal models that are used in studies of DNA repair in glioblastoma. We summarize recent progress in our knowledge of the pathways and factors involved in the removal of DNA lesions induced by ionizing radiation and temozolomide. We introduce the therapeutic strategies relying on DNA repair inhibitors that are currently being tested in vitro or in clinical trials, and present the challenges raised by drug delivery across the blood brain barrier as well as new opportunities in this field. Finally, we review the genetic and epigenetic alterations that help shape the DNA repair makeup of glioblastoma cells, and discuss their potential therapeutic impact and implications for personalized therapy. PMID:27543314

  6. Detection of polyomaviral DNA in clinical samples from immunocompromised patients: correlation with clinical disease.

    PubMed

    Perrons, C J; Fox, J D; Lucas, S B; Brink, N S; Tedder, R S; Miller, R F

    1996-05-01

    Clinical samples from immunocompromised patients were screened for polyomaviral sequences by nested polymerase chain reaction (PCR) to evaluate the association of these viral infections with progressive multifocal leukoencephalopathy (PML). JC virus (JCV) DNA was detected in 19 of 23 CSF samples and all four brain samples from patients with PML. Neither BK virus (BKV) nor simian virus 40 (SV40) DNA were detected in these samples. No evidence was found to support the hypothesis that polyomaviral DNA is present in the central nervous system of immunosuppressed patients without PML (CSF n = 67, brain n = 19). JCV DNA was not detected in any peripheral blood sample included in this study. JCV DNA was detected in urine from three of eight patients with PML, but was also amplified from three of 29 urine samples from patients without PML, JCV, and not SV40 or BKV, was associated with PML in this study. PMID:8793709

  7. Obtaining High Quality DNA from Diverse Clinical Samples.

    PubMed

    Melton-Kreft, Rachael; Spirk, Tracy

    2016-01-01

    Nucleic acids can be obtained in numerous ways from clinical specimens; however, the quality of the nucleic acid is only as good as the sampling and isolation protocol. While nucleic acids may be extracted they may not be representative of the original source. Large areas of tissue and explanted hardware must be successfully surveyed to reflect the overall clinical picture. Once good sampling technique has been established, successful bacterial nucleic acid isolation is essential. Clinical samples may be difficult to process because of the presence of scar tissue, bone, implants, and bacterial biofilms. The following protocols provide details on sampling techniques and DNA isolation from a variety of clinical samples which can then be used in downstream molecular applications including PCR-MS-ESI-TOF technology. © 2016 by John Wiley & Sons, Inc. PMID:26855284

  8. Color Histogram Diffusion for Image Enhancement

    NASA Technical Reports Server (NTRS)

    Kim, Taemin

    2011-01-01

    Various color histogram equalization (CHE) methods have been proposed to extend grayscale histogram equalization (GHE) for color images. In this paper a new method called histogram diffusion that extends the GHE method to arbitrary dimensions is proposed. Ranges in a histogram are specified as overlapping bars of uniform heights and variable widths which are proportional to their frequencies. This diagram is called the vistogram. As an alternative approach to GHE, the squared error of the vistogram from the uniform distribution is minimized. Each bar in the vistogram is approximated by a Gaussian function. Gaussian particles in the vistoram diffuse as a nonlinear autonomous system of ordinary differential equations. CHE results of color images showed that the approach is effective.

  9. Image enhancement by local histogram stretching

    NASA Astrophysics Data System (ADS)

    Alparslan, E.; Fuatince, Mr.

    1981-05-01

    An image enhancement algorithm that makes use of local histogram stretching is introduced. This algorithm yields considerable improvements in human observation of details in an image, compared to straightforward histogram equalization and a number of other enhancement techniques. The algorithm is especially suitable for producing hard copies of images on electrostatic plotters with limited gray levels, as shown in applications to the Girl's image and a Landsat image.

  10. Production of clinical-grade plasmid DNA for human Phase I clinical trials and large animal clinical studies.

    PubMed

    Przybylowski, Mark; Bartido, Shirley; Borquez-Ojeda, Oriana; Sadelain, Michel; Rivière, Isabelle

    2007-06-28

    The use of plasmid DNA as vaccines for the treatment of cancer and infectious diseases is on the rise. In order to facilitate the manufacture of clinical-grade plasmid DNA for Phase I clinical trials, we developed a process whereby >200 mg plasmid could be produced in a single production run under Good Manufacturing Practices. A dedicated cleanroom (Class 10,000 with Class 100 biosafety cabinet) is utilized for production of the bacterial cell bank, fermentation, harvest/lysis of the biomass, and downstream purification. Fermentation requires three 16-18 h runs (approximately 12 L each) in shaker-flasks, yielding approximately 60 g bacterial paste following batch centrifugation. The biomass is alkaline-lysed, pooled, and the resulting flocculent precipitate is separated by a novel vacuum step, followed by depth-filtration. Downstream processing includes anion-exchange chromatography, utilizing Qiagen silica-based resin, and precipitation with isopropanol. Following precipitation, the DNA is harvested by centrifugation, dried, formulated, and sterile-filtered using a Sartorius Sartobran 150 filter prior to Final-Filling. All processing steps utilize sterilized, single-use components. This process results in a product manufactured according to regulatory guidelines. The plasmid DNA is sterile with >or=95% supercoiled DNA, an A260/A280 ratio>or=1.9, undetectable or extremely low residual endotoxin, RNA, genomic DNA, protein, and antibiotic. Residual solvent levels are negligible. The product yields the predicted profile upon restriction-enzyme digestion, is biologically active upon transfection and remains stable for several years at -20 degrees C. We have therefore developed a reproducible and cost effective process to manufacture clinical-grade plasmid DNA. This process can be adapted by other academic centers for human or large animal clinical trials. PMID:17537555

  11. Retrospective Reconstructions of Active Bone Marrow Dose-Volume Histograms

    SciTech Connect

    Veres, Cristina; Allodji, Rodrigue S.; Llanas, Damien; Vu Bezin, Jérémi; Chavaudra, Jean; Mège, Jean Pierre; Lefkopoulos, Dimitri; Quiniou, Eric; Deutsh, Eric; Vathaire, Florent de; Diallo, Ibrahima

    2014-12-01

    Purpose: To present a method for calculating dose-volume histograms (DVH's) to the active bone marrow (ABM) of patients who had undergone radiation therapy (RT) and subsequently developed leukemia. Methods and Materials: The study focuses on 15 patients treated between 1961 and 1996. Whole-body RT planning computed tomographic (CT) data were not available. We therefore generated representative whole-body CTs similar to patient anatomy. In addition, we developed a method enabling us to obtain information on the density distribution of ABM all over the skeleton. Dose could then be calculated in a series of points distributed all over the skeleton in such a way that their local density reflected age-specific data for ABM distribution. Dose to particular regions and dose-volume histograms of the entire ABM were estimated for all patients. Results: Depending on patient age, the total number of dose calculation points generated ranged from 1,190,970 to 4,108,524. The average dose to ABM ranged from 0.3 to 16.4 Gy. Dose-volume histograms analysis showed that the median doses (D{sub 50%}) ranged from 0.06 to 12.8 Gy. We also evaluated the inhomogeneity of individual patient ABM dose distribution according to clinical situation. It was evident that the coefficient of variation of the dose for the whole ABM ranged from 1.0 to 5.7, which means that the standard deviation could be more than 5 times higher than the mean. Conclusions: For patients with available long-term follow-up data, our method provides reconstruction of dose-volume data comparable to detailed dose calculations, which have become standard in modern CT-based 3-dimensional RT planning. Our strategy of using dose-volume histograms offers new perspectives to retrospective epidemiological studies.

  12. Circle detection using scan lines and histograms

    NASA Astrophysics Data System (ADS)

    Chen, Ming; Zhang, Feng; Du, Zhenhong; Liu, Renyi

    2013-11-01

    Circle detection is significant in image processing and pattern recognition. We present a new algorithm for detecting circles, which is based on the global geometric symmetry of circles. First, the horizontal and vertical midpoint histograms of the edge image are obtained by using scan lines. Then, we apply the peak-finding algorithm to the midpoint histograms to look for the center of the circle. The normalized radius histogram is finally used to verify the existence of the circle and extract its radius. Synthetic images with different levels of pepper noise and real images containing several circles have been taken to test the performance. Experimental results demonstrate that the proposed algorithm has the advantage of computational efficiency as compared with the randomized Hough transform and some other algorithms.

  13. Quantization of color histograms using GLA

    NASA Astrophysics Data System (ADS)

    Yang, Christopher C.; Yip, Milo K.

    2002-09-01

    Color histogram has been used as one of the most important image descriptor in a wide range of content-based image retrieval (CBIR) projects for color image indexing. It captures the global chromatic distribution of an image. Traditionally, there are two major approaches to quantize the color space: (1) quantize each dimension of a color coordinate system uniformly to generate a fixed number of bins; and (2) quantize a color coordinate system arbitrarily. The first approach works best on cubical color coordinate systems, such as RGB. For other non-cubical color coordinate system, such as CIELAB and CIELUV, some bins may fall out of the gamut (transformed from the RGB cube) of the color space. As a result, it reduces the effectiveness of the color histogram and hence reduces the retrieval performance. The second approach uses arbitrarily quantization. The volume of the bins is not necessary uniform. As a result, it affects the effectiveness of the histogram significantly. In this paper, we propose to develop the color histogram by tessellating the non-cubical color gamut transformed from RGB cube using a vector quantization (VQ) method, the General Loyld Algorithm (GLA) [6]. Using such approach, the problem of empty bins due to the gamut of the color coordinate system can be avoided. Besides, all bins quantized by GLA will occupy the same volume. It guarantees that uniformity of each quantized bins in the histogram. An experiment has been conducted to evaluate the quantitative performance of our approach. The image collection from UC Berkeley's digital library project is used as the test bed. The indexing effectiveness of a histogram space [3] is used as the measurement of the performance. The experimental result shows that using the GLA quantization approach significantly increase the indexing effectiveness.

  14. Review: Clinical aspects of hereditary DNA Mismatch repair gene mutations.

    PubMed

    Sijmons, Rolf H; Hofstra, Robert M W

    2016-02-01

    Inherited mutations of the DNA Mismatch repair genes MLH1, MSH2, MSH6 and PMS2 can result in two hereditary tumor syndromes: the adult-onset autosomal dominant Lynch syndrome, previously referred to as Hereditary Non-Polyposis Colorectal Cancer (HNPCC) and the childhood-onset autosomal recessive Constitutional Mismatch Repair Deficiency syndrome. Both conditions are important to recognize clinically as their identification has direct consequences for clinical management and allows targeted preventive actions in mutation carriers. Lynch syndrome is one of the more common adult-onset hereditary tumor syndromes, with thousands of patients reported to date. Its tumor spectrum is well established and includes colorectal cancer, endometrial cancer and a range of other cancer types. However, surveillance for cancers other than colorectal cancer is still of uncertain value. Prophylactic surgery, especially for the uterus and its adnexa is an option in female mutation carriers. Chemoprevention of colorectal cancer with aspirin is actively being investigated in this syndrome and shows promising results. In contrast, the Constitutional Mismatch Repair Deficiency syndrome is rare, features a wide spectrum of childhood onset cancers, many of which are brain tumors with high mortality rates. Future studies are very much needed to improve the care for patients with this severe disorder. PMID:26746812

  15. Clinical experience with a recombinant DNA hepatitis B vaccine.

    PubMed

    Andre, F E

    1988-09-01

    The clinical testing of EngerixR-B, the hepatitis B vaccine produced by SmithKline Biologicals using recombinant DNA technology, started in February 1984. Since extensive pre-clinical laboratory work had established that the polypeptide (HBsAg) expressed in genetically engineered yeast cells was after purification--physically, chemically and antigenically similar to the viral surface antigen particles found in the blood of chronic carriers, the aims of the clinical trials were to compare the safety, reactogenicity, immunogenicity and protective efficacy of yeast-derived (YDV) and plasma-derived (PDV) vaccines. By September 1987, 89 studies had been initiated involving a total of 10,545 subjects aged from birth to 82 years. This extensive experience has established that the risk of hypersensitivity to yeast-derived contaminants is negligible since no hypersensitivity reaction has been observed in any vaccinee, the incidence and severity of local reactions have not increased after repeated inoculations and no anti-yeast antibodies were produced by vaccination. Reactogenicity has been comparable to that of PDV's consisting essentially of transient mild irritation at the site of injection presumably caused by the aluminium hydroxide used as adjuvant. The anti-HBs responses to YDV and PDV's were quantitatively (seroconversion rates, peak antibody levels and persistence) as well as qualitatively (epitope specificity and affinity) similar. The expected protective effect of the immune response to the vaccine was confirmed in a challenge study in chimpanzees and in vaccinated human populations (male homosexuals, institutionalized mentally retarded patients, neonates of carrier women) with historically a high infection rate. PMID:2464196

  16. Comparison and evaluation of joint histogram estimation methods for mutual information based image registration

    NASA Astrophysics Data System (ADS)

    Liang, Yongfang; Chen, Hua-mei

    2005-04-01

    Joint histogram is the only quantity required to calculate the mutual information (MI) between two images. For MI based image registration, joint histograms are often estimated through linear interpolation or partial volume interpolation (PVI). It has been pointed out that both methods may result in a phenomenon known as interpolation induced artifacts. In this paper, we implemented a wide range of interpolation/approximation kernels for joint histogram estimation. Some kernels are nonnegative. In this case, these kernels are applied in two ways as the linear kernel is applied in linear interpolation and PVI. In addition, we implemented two other joint histogram estimation methods devised to overcome the interpolation artifact problem. They are nearest neighbor interpolation with jittered sampling with/without histogram blurring and data resampling. We used the clinical data obtained from Vanderbilt University for all of the experiments. The objective of this study is to perform a comprehensive comparison and evaluation of different joint histogram estimation methods for MI based image registration in terms of artifacts reduction and registration accuracy.

  17. Unscheduled DNA Synthesis: The Clinical and Functional Assay for Global Genomic DNA Nucleotide Excision Repair

    PubMed Central

    Latimer, Jean J.; Kelly, Crystal M.

    2016-01-01

    The unscheduled DNA synthesis (UDS) assay measures the ability of a cell to perform global genomic nucleotide excision repair (NER). This chapter provides instructions for the application of this technique by creating 6-4 photoproducts and pyrimidine dimers using UV-C irradiation. This procedure is designed specifically for quantification of the 6-4 photoproducts. Repair is quantified by the amount of radioactive thymidine incorporated during repair synthesis after this insult, and radioactivity is evaluated by grain counting after autoradiography. The results are used to clinically diagnose human DNA repair deficiency disorders and provide a basis for investigation of repair deficiency in human tissues or tumors. No other functional assay is available that directly measures the capacity to perform NER on the entire genome without the use of specific antibodies. Since live cells are required for this assay, explant culture techniques must be previously established. Host cell reactivation (HCR), as discussed in Chapter 37, is not an equivalent technique, as it measures only transcription-coupled repair (TCR) at active genes, a small subset of total NER. PMID:24623250

  18. Advances in the medical research and clinical applications on the plasma DNA

    PubMed Central

    Chen, Yuanyuan; Wu, Zhanhe

    2014-01-01

    Plasma DNA has had a strong impact and influence on basic medical research and clinical practice since the discovery of low levels of plasma DNA in healthy individuals under different physiological conditions. Although the source of circulating DNA still requires further investigation, a wide range of research has also proven the value of qualitative and quantitative measurements of plasma DNA in many disease conditions. The use of plasma DNA has a biomarker is advantageous due to accessibility, reliability, reproducibility, sensitivity, specific and relatively low cost. Recently, the detection of circulating (plasma) DNA quantitative changes have been using in the studies on the tumor gene mutations and to monitor disease progressing and to predict the disease prognosis. Such technique also has been using other many different fields, particularly in prenatal diagnosis, for which plasma DNA testing is preferable due to non-invasiveness. This article reviews the research progression and clinical applications of plasma DNA in the last several years. PMID:26835332

  19. DNA damage in human skin fibroblasts exposed to UVA light used in clinical PUVA treatment

    SciTech Connect

    Bredberg, A.

    1981-06-01

    Human skin fibroblasts were irradiated with a clinically used UVA light source. The doses (1.1 and 3 J/cm2) were similar to those reaching the dermis during clinical PUVA treatment of psoriasis. DNA strand breaks, as determined by alkaline elution, were formed in a dose-dependent way and disappeared within 1 hr of postincubation at 37 degrees C. These findings have clinical implications since UVA-induced DNA damage may be accompanied by mutagenic and tumor promoting effects.

  20. Clinical development of intramuscular electroporation: providing a "boost" for DNA vaccines.

    PubMed

    Khan, Amir S; Broderick, Kate E; Sardesai, Niranjan Y

    2014-01-01

    The development of effective vaccines has helped to eradicate or control the spread of numerous infectious diseases. However, there are many more diseases that have proved more difficult to eliminate using conventional vaccines. The recent innovation of DNA vaccines may provide a "boost" to the development efforts. While the early efforts of DNA vaccines in the clinic were disappointing, the use of in vivo electroporation has helped to provide some basis for optimism. Now, there are several ongoing clinical studies of vaccines against such diseases as malaria, HIV, hepatitis C, and even various types of cancer. This review will highlight three recently published clinical studies using intramuscular DNA administration with electroporation. PMID:24510832

  1. DNA methylation analysis in constitutional disorders: Clinical implications of the epigenome.

    PubMed

    Schenkel, Laila C; Rodenhiser, David I; Ainsworth, Peter J; Paré, Guillaume; Sadikovic, Bekim

    2016-01-01

    Genomic, chromosomal, and gene-specific changes in the DNA sequence underpin both phenotypic variations in populations as well as disease associations, and the application of genomic technologies for the identification of constitutional (inherited) or somatic (acquired) alterations in DNA sequence forms a cornerstone of clinical and molecular genetics. In addition to the disruption of primary DNA sequence, the modulation of DNA function by epigenetic phenomena, in particular by DNA methylation, has long been known to play a role in the regulation of gene expression and consequent pathogenesis. However, these epigenetic factors have been identified only in a handful of pediatric conditions, including imprinting disorders. Technological advances in the past decade that have revolutionized clinical genomics are now rapidly being applied to the emerging discipline of clinical epigenomics. Here, we present an overview of epigenetic mechanisms with a focus on DNA modifications, including the molecular mechanisms of DNA methylation and subtypes of DNA modifications, and we describe the classic and emerging genomic technologies that are being applied to this study. This review focuses primarily on constitutional epigenomic conditions associated with a spectrum of developmental and intellectual disabilities. Epigenomic disorders are discussed in the context of global genomic disorders, imprinting disorders, and single gene disorders. We include a section focused on integration of genetic and epigenetic mechanisms together with their effect on clinical phenotypes. Finally, we summarize emerging epigenomic technologies and their impact on diagnostic aspects of constitutional genetic and epigenetic disorders. PMID:26758403

  2. Histogramming of the Charged Particle Measurements with MSL/RAD - Comparison of Histogram Data with Simulations

    NASA Astrophysics Data System (ADS)

    Ehresmann, B.; Zeitlin, C.; Hassler, D. M.; Wimmer-Schweingruber, R. F.; Boettcher, S.; Koehler, J.; Martin, C.; Brinza, D.; Rafkin, S. C.

    2012-12-01

    The Radiation Assessment Detector (RAD) on-board the Mars Science Laboratory (MSL) is designed to measure a broad range of energetic particle radiation. A significant part of this radiation consists of charged particles, which mainly stem from cosmic background radiation, Solar particle events, and secondaries created by the interaction of these particles with the Martian atmosphere and soil. To measure charged particles RAD is equipped with a set of detectors: a particle telescope consisting of three silicon Solid-State Detectors (SSDs), a CsI scintillator and a plastic scintillator, as well as a further plastic scintillator used as anti-coincidence. RAD uses an elaborate post-processing logic to analyze if a measured event qualifies as a charged particle, as well as to distinguish between particles stopping in any one of the detectors and particles penetrating the whole detector stack. RAD then arranges these qualifying events in an appropriate stopping or penetrating charged particle histogram, reducing the data volume necessary to maintain crucial information about the measured particle. For ground-based data analysis it is of prime importance to derive information, such as particle species or energy, from the data in the downloaded histograms. Here, we will present how the chosen binning of these histograms enables us to derive this information. Pre-flight, we used the Monte-Carlo code GEANT4 to simulate the expected particle radiation and its interactions with a full model of the RAD sensor head. By mirroring the on-board processing logic, we derived statistics of which particle species and energies populate any one bin in the set of charged particle histograms. Finally, we will compare the resulting histogram data from RAD cruise and surface observations with simulations. RAD is supported by NASA (HEOMD) under JPL subcontract #1273039 to SwRI, and by DLR in Germany under contract to Christian-Albrechts-Universitaet zu Kiel (CAU).

  3. Active steganalysis for histogram-shifting based reversible data hiding

    NASA Astrophysics Data System (ADS)

    Lou, Der-Chyuan; Chou, Chao-Lung; Tso, Hao-Kuan; Chiu, Chung-Cheng

    2012-05-01

    This paper presents an innovative active steganalysis algorithm for reversible data hiding schemes based on histogram shifting. These schemes use histogram shifting to embed secret data in cover-images. However, some histogram patterns originating during the embedding procedure may be recognized readily by a steganalyst. The proposed algorithm analyzes the characteristics of histogram changing during the data embedding procedure, and then models these features into reference templates by using a 1 × 4 sliding window. A support vector machine is trained as the classifier for discriminating between cover-images and stego-images by adopting the template matching techniques. The hidden messages located at the histogram peak of the cover-image were further estimated by measuring the feature of adjacent histogram differences. Experimental results indicate that the proposed active steganalysis algorithm can effectively detect stego-images at low bit rates and estimate the hidden messages locations.

  4. Using the gradient histogram to analyze the continuous phase plate

    NASA Astrophysics Data System (ADS)

    Yang, Chunlin

    2015-01-01

    The geometrical optical method has been used to discuss the far-field distribution characteristics of a continuous phase plate. The gradient histogram of the plate’s surface has been calculated. It has been proved that the gradient histogram can be used to show the angular spectrum of a phase plate. The gradient histogram can simplify the analysis process of the angular spectrum and describe the focal spot morphology more intuitively.

  5. Global DNA Methylation Level among Ciprofloxacin-Resistant Clinical Isolates of Escherichia coli

    PubMed Central

    Yugendran, Thiyagarajan

    2016-01-01

    Introduction Fluoroquinolone resistant clinical isolates belonging to the family Enterobacteriaceae is a major public health concern in India. Data analysis in JIPMER hospital revealed 10% rise in fluoroquinolone resistance within a span of three years suggestive of the possible involvement of mechanism/s other than QRDR capable of imparting fluoroquinolone resistance. DNA methylation regulates gene expression. Moreover, methylated cytosine is a mutational hotspot. Thus, DNA methylation can alter bacterial gene expression profile as well as facilitate the bacteria in accumulating mutations possibly leading to increased antimicrobial resistance. Therefore, the present study was carried out to identify the potential involvement of DNA methylation in ciprofloxacin resistance. Aim To elucidate and compare the methylation level of genomic and plasmid DNA among clinical isolates of E. coli sensitive and resistant to ciprofloxacin. Materials and Methods The study included 40 clinical E. coli isolates of which, 30 were ciprofloxacin-resistant and 10 were sensitive to ciprofloxacin. Genomic DNA (gDNA) and plasmid DNA were extracted and quantified. Methylation levels were elucidated using 5-mC DNA ELISA kit (Zymoresearch, California, USA) as per kit protocol and guidelines. Statistical Analysis Spearman correlation 2-tailed test. A p-value <0.05 was considered significant. Results The MIC values of sensitive and resistant strains against ciprofloxacin ranged from 0.125 μg/mL – 0.75 μg/mL and 8 μg/mL - >256 μg/mL respectively. No difference was found in plasmid DNA methylation level but, the gDNA methylation level of the resistant strains significantly differed from that of the sensitive strains. Based on Spearman correlation test gDNA methylation level of bacteria was found to be inversely proportional to its MIC against ciprofloxacin with p= -0.956 (p-value < 0.0001). Conclusion The influence of DNA methylation over plasmid-mediated quinolone resistance needs to be

  6. Clinical Radiation Sensitivity With DNA Repair Disorders: An Overview

    SciTech Connect

    Pollard, Julianne M.; Gatti, Richard A.

    2009-08-01

    Adverse reactions to radiotherapy represent a confounding phenomenon in radiation oncology. These reactions are rare, and many have been associated with individuals with DNA repair disorders such as ataxia-telangiectasia and Nijmegen Breakage syndrome. A paucity of published data is available detailing such circumstances. This overview describes four exemplary situations, a comprehensive list of 32 additional cases, and some insights gleaned from this overall experience. Fanconi anemia was associated with more than one-half of the reports. The lowest dose given to a patient that resulted in a reaction was 3 Gy, given to an ataxia-telangiectasia patient. Most patients died within months of exposure. It is clear that the patients discussed in this report had complicated illnesses, in addition to cancer, and the radiotherapy administered was most likely their best option. However, the underlying DNA repair defects make conventional radiation doses dangerous. Our findings support previous wisdom that radiotherapy should either be avoided or the doses should be selected with great care in the case of these radiosensitive genotypes, which must be recognized by their characteristic phenotypes, until more rapid, reliable, and functional assays of DNA repair become available.

  7. Clinical Radiation Sensitivity with DNA Repair Disorders: An Overview

    PubMed Central

    Pollard, Julianne M.; Gatti, Richard A.

    2009-01-01

    Adverse reactions to radiation therapy represent a confounding phenomenon in Radiation Oncology. These reactions are rare, and many have been associated with individuals with DNA repair disorders such as Ataxia-telangiectasia (A-T) and Nijmegen Breakage Syndrome (NBS). There is a paucity of literature detailing such circumstances. This overview describes four exemplary situations, a comprehensive list of 32 additional cases, and some insights gleaned from this overall experience. Fanconi Anemia was associated with over half of the reports. The lowest dose given to a patient that resulted in a reaction was 3 Gy, given to an A-T patient. Most patients died within months of exposure. It is clear that the patients discussed in this paper had complicated illnesses in addition to cancer, and the radiation therapy that administered was most likely their best option. However, the underlying DNA repair defects make conventional radiation therapy doses dangerous. Our review supports prior wisdom that radiation therapy should either be avoided, or doses should be selected with great care in the case of these radiosensitive genotypes which must be recognized with their characteristic phenotypes, until more rapid, reliable and functional assays of DNA repair become available. PMID:19616740

  8. Opto-electronic DNA chip-based integrated card for clinical diagnostics.

    PubMed

    Marchand, Gilles; Broyer, Patrick; Lanet, Véronique; Delattre, Cyril; Foucault, Frédéric; Menou, Lionel; Calvas, Bernard; Roller, Denis; Ginot, Frédéric; Campagnolo, Raymond; Mallard, Frédéric

    2008-02-01

    Clinical diagnostics is one of the most promising applications for microfluidic lab-on-a-chip or lab-on-card systems. DNA chips, which provide multiparametric data, are privileged tools for genomic analysis. However, automation of molecular biology protocol and use of these DNA chips in fully integrated systems remains a great challenge. Simplicity of chip and/or card/instrument interfaces is amongst the most critical issues to be addressed. Indeed, current detection systems for DNA chip reading are often complex, expensive, bulky and even limited in terms of sensitivity or accuracy. Furthermore, for liquid handling in the lab-on-cards, many devices use complex and bulky systems, either to directly manipulate fluids, or to ensure pneumatic or mechanical control of integrated valves. All these drawbacks prevent or limit the use of DNA-chip-based integrated systems, for point-of-care testing or as a routine diagnostics tool. We present here a DNA-chip-based protocol integration on a plastic card for clinical diagnostics applications including: (1) an opto-electronic DNA-chip, (2) fluid handling using electrically activated embedded pyrotechnic microvalves with closing/opening functions. We demonstrate both fluidic and electric packaging of the optoelectronic DNA chip without major alteration of its electronical and biological functionalities, and fluid control using novel electrically activable pyrotechnic microvalves. Finally, we suggest a complete design of a card dedicated to automation of a complex biological protocol with a fully electrical fluid handling and DNA chip reading. PMID:17636395

  9. Monitoring Incremental Histogram Distribution for Change Detection in Data Streams

    NASA Astrophysics Data System (ADS)

    Sebastião, Raquel; Gama, João; Rodrigues, Pedro Pereira; Bernardes, João

    Histograms are a common technique for density estimation and they have been widely used as a tool in exploratory data analysis. Learning histograms from static and stationary data is a well known topic. Nevertheless, very few works discuss this problem when we have a continuous flow of data generated from dynamic environments.

  10. Contrast enhancement via texture region based histogram equalization

    NASA Astrophysics Data System (ADS)

    Singh, Kuldeep; Vishwakarma, Dinesh K.; Singh Walia, Gurjit; Kapoor, Rajiv

    2016-08-01

    This paper presents two novel contrast enhancement approaches using texture regions-based histogram equalization (HE). In HE-based contrast enhancement methods, the enhanced image often contains undesirable artefacts because an excessive number of pixels in the non-textured areas heavily bias the histogram. The novel idea presented in this paper is to suppress the impact of pixels in non-textured areas and to exploit texture features for the computation of histogram in the process of HE. The first algorithm named as Dominant Orientation-based Texture Histogram Equalization (DOTHE), constructs the histogram of the image using only those image patches having dominant orientation. DOTHE categories image patches into smooth, dominant or non-dominant orientation patches by using the image variance and singular value decomposition algorithm and utilizes only dominant orientation patches in the process of HE. The second method termed as Edge-based Texture Histogram Equalization, calculates significant edges in the image and constructs the histogram using the grey levels present in the neighbourhood of edges. The cumulative density function of the histogram formed from texture features is mapped on the entire dynamic range of the input image to produce the contrast-enhanced image. Subjective as well as objective performance assessment of proposed methods is conducted and compared with other existing HE methods. The performance assessment in terms of visual quality, contrast improvement index, entropy and measure of enhancement reveals that the proposed methods outperform the existing HE methods.

  11. From data to probability densities without histograms

    NASA Astrophysics Data System (ADS)

    Berg, Bernd A.; Harris, Robert C.

    2008-09-01

    When one deals with data drawn from continuous variables, a histogram is often inadequate to display their probability density. It deals inefficiently with statistical noise, and binsizes are free parameters. In contrast to that, the empirical cumulative distribution function (obtained after sorting the data) is parameter free. But it is a step function, so that its differentiation does not give a smooth probability density. Based on Fourier series expansion and Kolmogorov tests, we introduce a simple method, which overcomes this problem. Error bars on the estimated probability density are calculated using a jackknife method. We give several examples and provide computer code reproducing them. You may want to look at the corresponding figures 4 to 9 first. Program summaryProgram title: cdf_to_pd Catalogue identifier: AEBC_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEBC_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 2758 No. of bytes in distributed program, including test data, etc.: 18 594 Distribution format: tar.gz Programming language: Fortran 77 Computer: Any capable of compiling and executing Fortran code Operating system: Any capable of compiling and executing Fortran code Classification: 4.14, 9 Nature of problem: When one deals with data drawn from continuous variables, a histogram is often inadequate to display the probability density. It deals inefficiently with statistical noise, and binsizes are free parameters. In contrast to that, the empirical cumulative distribution function (obtained after sorting the data) is parameter free. But it is a step function, so that its differentiation does not give a smooth probability density. Solution method: Based on Fourier series expansion and Kolmogorov tests, we introduce a simple method, which

  12. Comparison of Histograms for Use in Cloud Observation and Modeling

    NASA Technical Reports Server (NTRS)

    Green, Lisa; Xu, Kuan-Man

    2005-01-01

    Cloud observation and cloud modeling data can be presented in histograms for each characteristic to be measured. Combining information from single-cloud histograms yields a summary histogram. Summary histograms can be compared to each other to reach conclusions about the behavior of an ensemble of clouds in different places at different times or about the accuracy of a particular cloud model. As in any scientific comparison, it is necessary to decide whether any apparent differences are statistically significant. The usual methods of deciding statistical significance when comparing histograms do not apply in this case because they assume independent data. Thus, a new method is necessary. The proposed method uses the Euclidean distance metric and bootstrapping to calculate the significance level.

  13. Fast ordering algorithm for exact histogram specification.

    PubMed

    Nikolova, Mila; Steidl, Gabriele

    2014-12-01

    This paper provides a fast algorithm to order in a meaningful, strict way the integer gray values in digital (quantized) images. It can be used in any exact histogram specification-based application. Our algorithm relies on the ordering procedure based on the specialized variational approach. This variational method was shown to be superior to all other state-of-the art ordering algorithms in terms of faithful total strict ordering but not in speed. Indeed, the relevant functionals are in general difficult to minimize because their gradient is nearly flat over vast regions. In this paper, we propose a simple and fast fixed point algorithm to minimize these functionals. The fast convergence of our algorithm results from known analytical properties of the model. Our algorithm is equivalent to an iterative nonlinear filtering. Furthermore, we show that a particular form of the variational model gives rise to much faster convergence than other alternative forms. We demonstrate that only a few iterations of this filter yield almost the same pixel ordering as the minimizer. Thus, we apply only few iteration steps to obtain images, whose pixels can be ordered in a strict and faithful way. Numerical experiments confirm that our algorithm outperforms by far its main competitors. PMID:25347881

  14. DNA-PK mediates AKT activation and apoptosis inhibition in clinically acquired platinum resistance.

    PubMed

    Stronach, Euan A; Chen, Michelle; Maginn, Elaina N; Agarwal, Roshan; Mills, Gordon B; Wasan, Harpreet; Gabra, Hani

    2011-11-01

    Clinical resistance to chemotherapy is a frequent event in cancer treatment and is closely linked to poor outcome. High-grade serous (HGS) ovarian cancer is characterized by p53 mutation and high levels of genomic instability. Treatment includes platinum-based chemotherapy and initial response rates are high; however, resistance is frequently acquired, at which point treatment options are largely palliative. Recent data indicate that platinum-resistant clones exist within the sensitive primary tumor at presentation, implying resistant cell selection after treatment with platinum chemotherapy. The AKT pathway is central to cell survival and has been implicated in platinum resistance. Here, we show that platinum exposure induces an AKT-dependent, prosurvival, DNA damage response in clinically platinum-resistant but not platinum-sensitive cells. AKT relocates to the nucleus of resistant cells where it is phosphorylated specifically on S473 by DNA-dependent protein kinase (DNA-PK), and this activation inhibits cisplatin-mediated apoptosis. Inhibition of DNA-PK or AKT, but not mTORC2, restores platinum sensitivity in a panel of clinically resistant HGS ovarian cancer cell lines: we also demonstrate these effects in other tumor types. Resensitization is associated with prevention of AKT-mediated BAD phosphorylation. Strikingly, in patient-matched sensitive cells, we do not see enhanced apoptosis on combining cisplatin with AKT or DNA-PK inhibition. Insulin-mediated activation of AKT is unaffected by DNA-PK inhibitor treatment, suggesting that this effect is restricted to DNA damage-mediated activation of AKT and that, clinically, DNA-PK inhibition might prevent platinum-induced AKT activation without interfering with normal glucose homeostasis, an unwanted toxicity of direct AKT inhibitors. PMID:22131882

  15. DNA-PK Mediates AKT Activation and Apoptosis Inhibition in Clinically Acquired Platinum Resistance12

    PubMed Central

    Stronach, Euan A; Chen, Michelle; Maginn, Elaina N; Agarwal, Roshan; Mills, Gordon B; Wasan, Harpreet; Gabra, Hani

    2011-01-01

    Clinical resistance to chemotherapy is a frequent event in cancer treatment and is closely linked to poor outcome. High-grade serous (HGS) ovarian cancer is characterized by p53 mutation and high levels of genomic instability. Treatment includes platinum-based chemotherapy and initial response rates are high; however, resistance is frequently acquired, at which point treatment options are largely palliative. Recent data indicate that platinum-resistant clones exist within the sensitive primary tumor at presentation, implying resistant cell selection after treatment with platinum chemotherapy. The AKT pathway is central to cell survival and has been implicated in platinum resistance. Here, we show that platinum exposure induces an AKT-dependent, prosurvival, DNA damage response in clinically platinum-resistant but not platinum-sensitive cells. AKT relocates to the nucleus of resistant cells where it is phosphorylated specifically on S473 by DNA-dependent protein kinase (DNA-PK), and this activation inhibits cisplatin-mediated apoptosis. Inhibition of DNA-PK or AKT, but not mTORC2, restores platinum sensitivity in a panel of clinically resistant HGS ovarian cancer cell lines: we also demonstrate these effects in other tumor types. Resensitization is associated with prevention of AKT-mediated BAD phosphorylation. Strikingly, in patient-matched sensitive cells, we do not see enhanced apoptosis on combining cisplatin with AKT or DNA-PK inhibition. Insulin-mediated activation of AKT is unaffected by DNA-PK inhibitor treatment, suggesting that this effect is restricted to DNA damage-mediated activation of AKT and that, clinically, DNA-PK inhibition might prevent platinum-induced AKT activation without interfering with normal glucose homeostasis, an unwanted toxicity of direct AKT inhibitors. PMID:22131882

  16. Mitochondria DNA Change and Oxidative Damage in Clinically Stable Patients with Major Depressive Disorder

    PubMed Central

    Chang, Cheng-Chen; Jou, Shaw-Hwa; Lin, Ta-Tsung

    2015-01-01

    Background To compare alterations of mitochondria DNA (mtDNA) copy number, single nucleotide polymorphisms (SNPs), and oxidative damage of mtDNA in clinically stable patients with major depressive disorder (MDD). Methods Patients met DSM-IV diagnostic criteria for MDD were recruited from the psychiatric outpatient clinic at Changhua Christian Hospital, Taiwan. They were clinically stable and their medications had not changed for at least the preceding two months. Exclusion criteria were substance-induced psychotic disorder, eating disorder, anxiety disorder or illicit substance abuse. Comparison subjects did not have any major psychiatric disorder and they were medically healthy. Peripheral blood leukocytes were analyzed to compare copy number, SNPs and oxidative damage of mtDNA between the two groups. Results 40 MDD patients and 70 comparison subjects were collected. The median age of the subjects was 42 years and 38 years in MDD and comparison groups, respectively. Leukocyte mtDNA copy number of MDD patients was significantly lower than that of the comparison group (p = 0.037). MDD patients had significantly higher mitochondrial oxidative damage than the comparison group (6.44 vs. 3.90, p<0.001). After generalized linear model adjusted for age, sex, smoking, family history, and psychotropic use, mtDNA copy number was still significantly lower in the MDD group (p<0.001). MtDNA oxidative damage was positively correlated with age (p<0.001) and MDD (p<0.001). Antipsychotic use was negatively associated with mtDNA copy number (p = 0.036). Limitations The study is cross-sectional with no longitudinal follow up. The cohort is clinically stable and generalizability of our result to other cohort should be considered. Conclusions Our study suggests that oxidative stress and mitochondria may play a role in the pathophysiology of MDD. More large-scale studies are warranted to assess the interplay between oxidative stress, mitochondria dysfunction and MDD. PMID:25946463

  17. Qualification Study of Two Genomic DNA Extraction Methods in Different Clinical Samples

    PubMed Central

    Javadi, Alireza; Shamaei, Masoud; Pourabdollah, Mihan; Dorudinia, Atosa; Seyedmehdi, Seyed Mohammad; Karimi, Shirin

    2014-01-01

    Introduction The purity of genomic DNA (gDNA) extracted from different clinical specimens optimizes sensitivity of polymerase chain reaction (PCR) assays. This study attempted to compare two different DNA extraction techniques namely salting-out and classic phenol-chloroform. Materials and Methods Qualification of two different DNA extraction techniques for 634 clinical specimens highly suspected of having mycobacterial infection was performed. Genomic DNA was extracted from 330 clinical samples using phenol-chloroform and 304 by non-toxic salting-out. Qualification of obtained gDNA was done through amplification of internal controls, β-actin and β-globin. Results β-actin-positive was detected in 279/330 (84%) and 272/304 (89%) samples by phenol-chloroform technique and salting-out, respectively. PCR inhibitor was found for the gDNA of 13/304 (4%) patient samples were negative by β-actin and β-globin tests via salting-out technique in comparison with gDNAs from 27/330 (8.5%) samples extracted by phenol-chloroform procedure. No statistically significant difference was found between phenol-chloroform technique and salting-out for 385 sputum, 29 bronchoalveolar lavage (BAL), 105 gastric washing, and 38 body fluid (P=0.04) samples. This illustrates that both techniques have the same quality for extracting gDNA. Conclusion This study discloses salting-out as a non-toxic DNA extraction procedure with a superior time-efficiency and cost-effectiveness in comparison with phenol-chloroform and it can be routinely used in resource-limited laboratory settings. PMID:25852760

  18. Using data mining to characterize DNA mutations by patient clinical features.

    PubMed Central

    Evans, S.; Lemon, S. J.; Deters, C.; Fusaro, R. M.; Durham, C.; Snyder, C.; Lynch, H. T.

    1997-01-01

    In most hereditary cancer syndromes, finding a correspondence between various genetic mutations within a gene (genotype) and a patient's clinical cancer history (phenotype) is challenging; to date there are few clinically meaningful correlations between specific DNA intragenic mutations and corresponding cancer types. To define possible genotype and phenotype correlations, we evaluated the application of data mining methodology whereby the clinical cancer histories of gene-mutation-positive patients were used to define valid or "true" patterns for a specific DNA intragenic mutation. The clinical histories of patients with their corresponding detailed attributes without the same oncologic intragenic mutation were labeled incorrect or "false" patterns. The results of data mining technology yielded characterizing rules for the true cases that constituted clinical features which predicted the intragenic mutation. Some of the initial results derived correlations already independently known in the literature, adding to the confidence of using this methodological approach. PMID:9357627

  19. Sperm DNA damage and its clinical relevance in assessing reproductive outcome.

    PubMed

    Sharma, R K; Said, T; Agarwal, A

    2004-06-01

    The routine examination of semen, which assesses sperm concentration, percentage motility and morphology, does not identify subtle defects in sperm chromatin architecture. The focus on the genomic integrity of the male gamete has intensified recently due to the growing concern that genetic diseases may be transmitted via assisted reproductive techniques (ART). Accordingly, the intent of this review is to describe the details of the information pertaining to mitochondrial/nuclear sperm DNA damage with an emphasis on its clinical significance and its relationship with male infertility. Assessment of sperm DNA damage appears to be a potential tool for evaluating semen samples prior to their use in ART. Testing DNA integrity may help select spermatozoa with intact DNA or with the least amount of DNA damage for use in assisted conception. In turn, this may alleviate the financial, social and emotional problems associated with failed ART attempts. PMID:15154089

  20. AHIMSA - Ad hoc histogram information measure sensing algorithm for feature selection in the context of histogram inspired clustering techniques

    NASA Technical Reports Server (NTRS)

    Dasarathy, B. V.

    1976-01-01

    An algorithm is proposed for dimensionality reduction in the context of clustering techniques based on histogram analysis. The approach is based on an evaluation of the hills and valleys in the unidimensional histograms along the different features and provides an economical means of assessing the significance of the features in a nonparametric unsupervised data environment. The method has relevance to remote sensing applications.

  1. Mitochondrial DNA Variation and Heteroplasmy in Monozygotic Twins Clinically Discordant for Multiple Sclerosis.

    PubMed

    Souren, Nicole Y P; Gerdes, Lisa A; Kümpfel, Tania; Lutsik, Pavlo; Klopstock, Thomas; Hohlfeld, Reinhard; Walter, Jörn

    2016-08-01

    We examined the debated link between mitochondrial DNA (mtDNA) variation and multiple sclerosis (MS) using 49 monozygotic (MZ) twin pairs clinically discordant for MS, which enables to associate de novo mtDNA variants, skewed heteroplasmy, and mtDNA copy number with MS manifestation. Ultra-deep sequencing of blood-derived mtDNA revealed 25 heteroplasmic variants with potentially pathogenic features in 18 pairs. All variants were pair-specific and had low and/or similar heteroplasmy levels in both cotwins. In one pair, a confirmed pathogenic variant (m.11778G>A, heteroplasmy ∼50%) associated with Leber hereditary optic neuropathy was detected. Detailed diagnostic investigation revealed subclinical MS signs in the prior nondiseased cotwin. Moreover, neither mtDNA deletions nor copy-number variations were involved. Furthermore, the majority of heteroplasmic variants were shared among MZ twins and exhibited more similar heteroplasmy levels in the same tissue of MZ twins as compared with different tissues of the same individual. Heteroplasmy levels were also more similar within MZ twins compared with nonidentical siblings. Our analysis excludes mtDNA variation as a major driver of the discordant clinical manifestation of MS in MZ twins, and provides valuable insights into the occurrence and distribution of heteroplasmic variants within MZ twins and nonidentical siblings, and across different tissues. PMID:27119776

  2. A comparison of ARMS and DNA sequencing for mutation analysis in clinical biopsy samples

    PubMed Central

    2010-01-01

    Background We have compared mutation analysis by DNA sequencing and Amplification Refractory Mutation System™ (ARMS™) for their ability to detect mutations in clinical biopsy specimens. Methods We have evaluated five real-time ARMS assays: BRAF 1799T>A, [this includes V600E and V600K] and NRAS 182A>G [Q61R] and 181C>A [Q61K] in melanoma, EGFR 2573T>G [L858R], 2235-2249del15 [E746-A750del] in non-small-cell lung cancer, and compared the results to DNA sequencing of the mutation 'hot-spots' in these genes in formalin-fixed paraffin-embedded tumour (FF-PET) DNA. Results The ARMS assays maximised the number of samples that could be analysed when both the quality and quantity of DNA was low, and improved both the sensitivity and speed of analysis compared with sequencing. ARMS was more robust with fewer reaction failures compared with sequencing and was more sensitive as it was able to detect functional mutations that were not detected by DNA sequencing. DNA sequencing was able to detect a small number of lower frequency recurrent mutations across the exons screened that were not interrogated using the specific ARMS assays in these studies. Conclusions ARMS was more sensitive and robust at detecting defined somatic mutations than DNA sequencing on clinical samples where the predominant sample type was FF-PET. PMID:20925915

  3. Progressive reversion of clinical and molecular phenotype in a child with liver mitochondrial DNA depletion.

    PubMed

    Ducluzeau, Pierre-Henri; Lachaux, Alain; Bouvier, Raymonde; Duborjal, Hervé; Stepien, Georges; Bozon, Dominique; Mousson de Camaret, Bénédicte

    2002-05-01

    Mitochondrial DNA depletion is a well established cause of severe liver failure in infancy. The autosomal inheritance of this quantitative mitochondrial DNA defect supports the involvement of a nuclear gene in the control of mitochondrial DNA level. We previously described a case of a 28-month-old child presenting with a progressive liver fibrosis due to a mitochondrial DNA depletion (85% at 12 months of age). As this syndrome was clinically liver-restricted, a liver transplant was initially discussed. We report the clinical, biochemical and molecular follow-up of this child, now 6 years old. The patient displayed a spontaneous gradual improvement of his liver function with continuous increment of clotting factor values since 32 months of age. A marked reduction of the previous extensive fibrosis was evidenced on a liver biopsy performed at 46 months of age associated with a dramatic decrease of the mitochondrial DNA depletion (35%). Consequently, an almost complete restoration of respiratory chain activities containing mitochondrial DNA-encoded subunits was observed. This is the first report of a revertant phenotype in liver mitochondrial DNA depletion syndrome. PMID:11983456

  4. Taking electroporation-based delivery of DNA vaccination into humans: a generic clinical protocol.

    PubMed

    Tjelle, Torunn Elisabeth; Rabussay, Dietmar; Ottensmeier, Christian; Mathiesen, Iacob; Kjeken, Rune

    2008-01-01

    We are presently aware of two early-phase DNA vaccine clinical trials in humans using electroporation-enhanced vaccine delivery. Moreover, two phase I immunogenetherapy studies are in progress and several tolerability studies have been performed on healthy volunteers. We have used knowledge from these studies to compose a template for clinical protocols involving electroporation-mediated gene delivery. In this template the emphasis will be on aspects related to electroporation. In addition, we will discuss general topics concerning electroporation-augmented DNA vaccination in human subjects. PMID:18370225

  5. Cardiac involvement in mitochondrial DNA disease: clinical spectrum, diagnosis, and management

    PubMed Central

    Bates, Matthew G. D.; Bourke, John P.; Giordano, Carla; d'Amati, Giulia; Turnbull, Douglass M.; Taylor, Robert W.

    2012-01-01

    Mitochondrial disease refers to a heterogenous group of genetic disorders that result from dysfunction of the final common pathway of energy metabolism. Mitochondrial DNA mutations affect key components of the respiratory chain and account for the majority of mitochondrial disease in adults. Owing to critical dependence of the heart on oxidative metabolism, cardiac involvement in mitochondrial disease is common and may occur as the principal clinical manifestation or part of multisystem disease. Recent advances in our understanding of the clinical spectrum and genetic aetiology of cardiac involvement in mitochondrial DNA disease have important implications for cardiologists in terms of the investigation and multi-disciplinary management of patients. PMID:22936362

  6. Simple, Sensitive and Accurate Multiplex Detection of Clinically Important Melanoma DNA Mutations in Circulating Tumour DNA with SERS Nanotags

    PubMed Central

    Wee, Eugene J.H.; Wang, Yuling; Tsao, Simon Chang-Hao; Trau, Matt

    2016-01-01

    Sensitive and accurate identification of specific DNA mutations can influence clinical decisions. However accurate diagnosis from limiting samples such as circulating tumour DNA (ctDNA) is challenging. Current approaches based on fluorescence such as quantitative PCR (qPCR) and more recently, droplet digital PCR (ddPCR) have limitations in multiplex detection, sensitivity and the need for expensive specialized equipment. Herein we describe an assay capitalizing on the multiplexing and sensitivity benefits of surface-enhanced Raman spectroscopy (SERS) with the simplicity of standard PCR to address the limitations of current approaches. This proof-of-concept method could reproducibly detect as few as 0.1% (10 copies, CV < 9%) of target sequences thus demonstrating the high sensitivity of the method. The method was then applied to specifically detect three important melanoma mutations in multiplex. Finally, the PCR/SERS assay was used to genotype cell lines and ctDNA from serum samples where results subsequently validated with ddPCR. With ddPCR-like sensitivity and accuracy yet at the convenience of standard PCR, we believe this multiplex PCR/SERS method could find wide applications in both diagnostics and research. PMID:27446486

  7. Accuracy of the Clinical Diagnosis of Vaginitis Compared to a DNA Probe Laboratory Standard

    PubMed Central

    Lowe, Nancy K.; Neal, Jeremy L.; Ryan-Wenger, Nancy A.

    2009-01-01

    Objective To estimate the accuracy of the clinical diagnosis of the three most common causes of acute vulvovaginal symptoms (bacterial vaginosis, candidiasis vaginitis, and trichomoniasis vaginalis) using a traditional, standardized clinical diagnostic protocol compared to a DNA probe laboratory standard. Methods This prospective clinical comparative study had a sample of 535 active duty United States military women presenting with vulovaginal symptoms. Clinical diagnoses were made by research staff using a standardized protocol of history, physical examination including pelvic examination, determination of vaginal pH, vaginal fluid amines test, and wet-prep microscopy. Vaginal fluid samples were obtained for DNA analysis. The research clinicians were blinded to the DNA results. Results The participants described a presenting symptom of abnormal discharge (50%), itching/irritation (33%), malodor (10%), burning (4%), or others such as vulvar pain and vaginal discomfort. According to laboratory standard, there were 225 cases (42%) of bacterial vaginosis 76 cases (14%) of candidiasis vaginitis, 8 cases (1.5%) of trichomoniasis vaginalis, 87 cases of mixed infections (16%), and 139 negative cases (26%). For each single infection, the clinical diagnosis had a sensitivity and specificity of 80.8% and 70.0% for bacterial vaginosis; 83.8% and 84.8% for candidiasis vaginitis; and 84.6% and 99.6% for trichomoniasis vaginalis when compared to the DNA probe standard. Conclusion Compared to a DNA probe standard, clinical diagnosis is 81-85% sensitive and 70- 99% specific for bacterial vaginosis, candida vaginitis, and trichomoniasis. Even under research conditions that provided clinicians with sufficient time and materials to conduct a thorough and standardized clinical evaluation, the diagnosis and therefore, subsequent treatment of these common vaginal problems remains difficult. PMID:19104364

  8. Clinical utility of circulating tumor DNA for molecular assessment in pancreatic cancer

    PubMed Central

    Takai, Erina; Totoki, Yasushi; Nakamura, Hiromi; Morizane, Chigusa; Nara, Satoshi; Hama, Natsuko; Suzuki, Masami; Furukawa, Eisaku; Kato, Mamoru; Hayashi, Hideyuki; Kohno, Takashi; Ueno, Hideki; Shimada, Kazuaki; Okusaka, Takuji; Nakagama, Hitoshi; Shibata, Tatsuhiro; Yachida, Shinichi

    2015-01-01

    Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies. The genomic landscape of the PDAC genome features four frequently mutated genes (KRAS, CDKN2A, TP53, and SMAD4) and dozens of candidate driver genes altered at low frequency, including potential clinical targets. Circulating cell-free DNA (cfDNA) is a promising resource to detect and monitor molecular characteristics of tumors. In the present study, we determined the mutational status of KRAS in plasma cfDNA using multiplex picoliter-droplet digital PCR in 259 patients with PDAC. We constructed a novel modified SureSelect-KAPA-Illumina platform and an original panel of 60 genes. We then performed targeted deep sequencing of cfDNA and matched germline DNA samples in 48 patients who had ≥1% mutant allele frequencies of KRAS in plasma cfDNA. Importantly, potentially targetable somatic mutations were identified in 14 of 48 patients (29.2%) examined by targeted deep sequencing of cfDNA. We also analyzed somatic copy number alterations based on the targeted sequencing data using our in-house algorithm, and potentially targetable amplifications were detected. Assessment of mutations and copy number alterations in plasma cfDNA may provide a prognostic and diagnostic tool to assist decisions regarding optimal therapeutic strategies for PDAC patients. PMID:26669280

  9. A spectral histogram model for texton modeling and texture discrimination.

    PubMed

    Liu, Xiuwen; Wang, DeLiang

    2002-10-01

    We suggest a spectral histogram, defined as the marginal distribution of filter responses, as a quantitative definition for a texton pattern. By matching spectral histograms, an arbitrary image can be transformed to an image with similar textons to the observed. We use the chi(2)-statistic to measure the difference between two spectral histograms, which leads to a texture discrimination model. The performance of the model well matches psychophysical results on a systematic set of texture discrimination data and it exhibits the nonlinearity and asymmetry phenomena in human texture discrimination. A quantitative comparison with the Malik-Perona model is given, and a number of issues regarding the model are discussed. PMID:12446034

  10. Principal component analysis of the CT density histogram to generate parametric response maps of COPD

    NASA Astrophysics Data System (ADS)

    Zha, N.; Capaldi, D. P. I.; Pike, D.; McCormack, D. G.; Cunningham, I. A.; Parraga, G.

    2015-03-01

    Pulmonary x-ray computed tomography (CT) may be used to characterize emphysema and airways disease in patients with chronic obstructive pulmonary disease (COPD). One analysis approach - parametric response mapping (PMR) utilizes registered inspiratory and expiratory CT image volumes and CT-density-histogram thresholds, but there is no consensus regarding the threshold values used, or their clinical meaning. Principal-component-analysis (PCA) of the CT density histogram can be exploited to quantify emphysema using data-driven CT-density-histogram thresholds. Thus, the objective of this proof-of-concept demonstration was to develop a PRM approach using PCA-derived thresholds in COPD patients and ex-smokers without airflow limitation. Methods: Fifteen COPD ex-smokers and 5 normal ex-smokers were evaluated. Thoracic CT images were also acquired at full inspiration and full expiration and these images were non-rigidly co-registered. PCA was performed for the CT density histograms, from which the components with the highest eigenvalues greater than one were summed. Since the values of the principal component curve correlate directly with the variability in the sample, the maximum and minimum points on the curve were used as threshold values for the PCA-adjusted PRM technique. Results: A significant correlation was determined between conventional and PCA-adjusted PRM with 3He MRI apparent diffusion coefficient (p<0.001), with CT RA950 (p<0.0001), as well as with 3He MRI ventilation defect percent, a measurement of both small airways disease (p=0.049 and p=0.06, respectively) and emphysema (p=0.02). Conclusions: PRM generated using PCA thresholds of the CT density histogram showed significant correlations with CT and 3He MRI measurements of emphysema, but not airways disease.

  11. Impact of sperm DNA chromatin in the clinic.

    PubMed

    Ioannou, Dimitrios; Miller, David; Griffin, Darren K; Tempest, Helen G

    2016-02-01

    The paternal contribution to fertilization and embryogenesis is frequently overlooked as the spermatozoon is often considered to be a silent vessel whose only function is to safely deliver the paternal genome to the maternal oocyte. In this article, we hope to demonstrate that this perception is far from the truth. Typically, infertile men have been unable to conceive naturally (or through regular IVF), and therefore, a perturbation of the genetic integrity of sperm heads in infertile males has been under-considered. The advent of intracytoplasmic sperm injection (ICSI) however has led to very successful treatment of male factor infertility and subsequent widespread use in IVF clinics worldwide. Until recently, little concern has been raised about the genetic quality of sperm in ICSI patients or the impact genetic aberrations could have on fertility and embryogenesis. This review highlights the importance of chromatin packaging in the sperm nucleus as essential for the establishment and maintenance of a viable pregnancy. PMID:26678492

  12. Regulators Associated with Clinical Outcomes Revealed by DNA Methylation Data in Breast Cancer

    PubMed Central

    Ung, Matthew H.; Varn, Frederick S.; Lou, Shaoke; Cheng, Chao

    2015-01-01

    The regulatory architecture of breast cancer is extraordinarily complex and gene misregulation can occur at many levels, with transcriptional malfunction being a major cause. This dysfunctional process typically involves additional regulatory modulators including DNA methylation. Thus, the interplay between transcription factor (TF) binding and DNA methylation are two components of a cancer regulatory interactome presumed to display correlated signals. As proof of concept, we performed a systematic motif-based in silico analysis to infer all potential TFs that are involved in breast cancer prognosis through an association with DNA methylation changes. Using breast cancer DNA methylation and clinical data derived from The Cancer Genome Atlas (TCGA), we carried out a systematic inference of TFs whose misregulation underlie different clinical subtypes of breast cancer. Our analysis identified TFs known to be associated with clinical outcomes of p53 and ER (estrogen receptor) subtypes of breast cancer, while also predicting new TFs that may also be involved. Furthermore, our results suggest that misregulation in breast cancer can be caused by the binding of alternative factors to the binding sites of TFs whose activity has been ablated. Overall, this study provides a comprehensive analysis that links DNA methylation to TF binding to patient prognosis. PMID:25996148

  13. Evaluation of urinary metal concentrations and sperm DNA damage in infertile men from an infertility clinic.

    PubMed

    Zhou, Yan; Fu, Xiao-Ming; He, Dong-Liang; Zou, Xue-Min; Wu, Cheng-Qiu; Guo, Wei-Zhen; Feng, Wei

    2016-07-01

    This study aimed to examine associations between urinary metal concentrations and sperm DNA damage. Thirteen metals [arsenic (As), cadmium (Cd), cobalt (Co), chromium (Cr), copper (Cu), iron (Fe), lead (Pb), manganese (Mn), molybdenum (Mo), mercury (Hg), nickel (Ni), selenium (Se), and zinc (Zn)] were detected in urine samples of 207 infertile men from an infertility clinic using inductively coupled plasma mass spectrometry, and also, sperm DNA damage (tail length, percent DNA tail, and tail distributed moment) were assessed using neutral comet assay. We found that urinary Hg and Ni were associated with increasing trends for tail length (both p for trend<0.05), and that urinary Mn was associated with increasing trend for tail distributed moment (p for trend=0.02). These associations did persist even when considering multiple metals. Our results suggest that environmental exposure to Hg, Mn, and Ni may be associated with increased sperm DNA damage. PMID:27262988

  14. Colorimetric detection of clinical DNA samples using an intercalator-conjugated polydiacetylene sensor.

    PubMed

    Jung, Yun Kyung; Park, Hyun Gyu

    2015-10-15

    We herein developed a novel colorimetric polydiacetylene (PDA) sensor for very convenient detection of clinical DNA samples based on the interaction between an intercalator and dsDNA. We modified the terminal carboxyl group of a diacetylene monomer (10,12-pentacosadiynoic acid; PCDA) with the intercalator 9-aminoacridine (9AA) and prepared 9AA-modified PDA liposomes containing PCDA-9AA/PCDA/phospholipid (1,2-dimyristoyl-rac-glycero-3-phosphocholine) at a molar ratio of 1.5:6.5:2.0. The PDA sensor underwent an obvious color transition from blue to red in the presence of dsDNA molecules that were PCR-amplified from genomic DNA due to the insertion of the 9AA head group of PDA into the dsDNA. DNA concentrations as low as 20 nM and relatively small molecules (around 100 base pairs) could be detected by the sensor within 1h without DNA electrophoresis. This novel colorimetric method is simple, does not require any instrument, and is therefore appropriate for POCT or portable molecular diagnostic kit. PMID:25978440

  15. DNA Methylation as Clinically Useful Biomarkers—Light at the End of the Tunnel

    PubMed Central

    Levenson, Victor V.; Melnikov, Anatoliy A.

    2012-01-01

    A recent expansion of our knowledge about epigenetic changes strongly suggests that epigenetic rather than genetic features better reflect disease development, and consequently, can become more conclusive biomarkers for the detection and diagnosis of different diseases. In this paper we will concentrate on the current advances in DNA methylation studies that demonstrate a direct link between abnormal DNA methylation and a disease. This link can be used to develop diagnostic biomarkers that will precisely identify a particular disease. It also appears that disease-specific DNA methylation patterns undergo unique changes in response to treatment with a particular drug, thus raising the possibility of DNA methylation-based biomarkers for the monitoring of treatment efficacy, for prediction of response to treatment, and for the prognosis of outcome. While biomarkers for oncology are the most obvious applications, other fields of medicine are likely to benefit as well. This potential is demonstrated by DNA methylation-based biomarkers for neurological and psychiatric diseases. A special requirement for a biomarker is the possibility of longitudinal testing. In this regard cell-free circulating DNA from blood is especially interesting because it carries methylation markers specific for a particular disease. Although only a few DNA methylation-based biomarkers have attained clinical relevance, the ongoing efforts to decipher disease-specific methylation patterns are likely to produce additional biomarkers for detection, diagnosis, and monitoring of different diseases in the near future. PMID:24288045

  16. Action recognition via cumulative histogram of multiple features

    NASA Astrophysics Data System (ADS)

    Yan, Xunshi; Luo, Yupin

    2011-01-01

    Spatial-temporal interest points (STIPs) are popular in human action recognition. However, they suffer from difficulties in determining size of codebook and losing much information during forming histograms. In this paper, spatial-temporal interest regions (STIRs) are proposed, which are based on STIPs and are capable of marking the locations of the most ``shining'' human body parts. In order to represent human actions, the proposed approach takes great advantages of multiple features, including STIRs, pyramid histogram of oriented gradients and pyramid histogram of oriented optical flows. To achieve this, cumulative histogram is used to integrate dynamic information in sequences and to form feature vectors. Furthermore, the widely used nearest neighbor and AdaBoost methods are employed as classification algorithms. Experiments on public datasets KTH, Weizmann and UCF sports show that the proposed approach achieves effective and robust results.

  17. Approximate Splitting for Ensembles of Trees using Histograms

    SciTech Connect

    Kamath, C; Cantu-Paz, E; Littau, D

    2001-09-28

    Recent work in classification indicates that significant improvements in accuracy can be obtained by growing an ensemble of classifiers and having them vote for the most popular class. Implicit in many of these techniques is the concept of randomization that generates different classifiers. In this paper, they focus on ensembles of decision trees that are created using a randomized procedure based on histograms. Techniques, such as histograms, that discretize continuous variables, have long been used in classification to convert the data into a form suitable for processing and to reduce the compute time. The approach combines the ideas behind discretization through histograms and randomization in ensembles to create decision trees by randomly selecting a split point in an interval around the best bin boundary in the histogram. The experimental results with public domain data show that ensembles generated using this approach are competitive in accuracy and superior in computational cost to other ensembles techniques such as boosting and bagging.

  18. Using color histograms and SPA-LDA to classify bacteria.

    PubMed

    de Almeida, Valber Elias; da Costa, Gean Bezerra; de Sousa Fernandes, David Douglas; Gonçalves Dias Diniz, Paulo Henrique; Brandão, Deysiane; de Medeiros, Ana Claudia Dantas; Véras, Germano

    2014-09-01

    In this work, a new approach is proposed to verify the differentiating characteristics of five bacteria (Escherichia coli, Enterococcus faecalis, Streptococcus salivarius, Streptococcus oralis, and Staphylococcus aureus) by using digital images obtained with a simple webcam and variable selection by the Successive Projections Algorithm associated with Linear Discriminant Analysis (SPA-LDA). In this sense, color histograms in the red-green-blue (RGB), hue-saturation-value (HSV), and grayscale channels and their combinations were used as input data, and statistically evaluated by using different multivariate classifiers (Soft Independent Modeling by Class Analogy (SIMCA), Principal Component Analysis-Linear Discriminant Analysis (PCA-LDA), Partial Least Squares Discriminant Analysis (PLS-DA) and Successive Projections Algorithm-Linear Discriminant Analysis (SPA-LDA)). The bacteria strains were cultivated in a nutritive blood agar base layer for 24 h by following the Brazilian Pharmacopoeia, maintaining the status of cell growth and the nature of nutrient solutions under the same conditions. The best result in classification was obtained by using RGB and SPA-LDA, which reached 94 and 100 % of classification accuracy in the training and test sets, respectively. This result is extremely positive from the viewpoint of routine clinical analyses, because it avoids bacterial identification based on phenotypic identification of the causative organism using Gram staining, culture, and biochemical proofs. Therefore, the proposed method presents inherent advantages, promoting a simpler, faster, and low-cost alternative for bacterial identification. PMID:25023972

  19. Low Mitochondrial DNA Copy Number is Associated With Adverse Clinical Outcomes in Peritoneal Dialysis Patients.

    PubMed

    Yoon, Chang-Yun; Park, Jung Tak; Kee, Youn Kyung; Han, Seung Gyu; Han, In Mee; Kwon, Young Eun; Park, Kyoung Sook; Lee, Mi Jung; Han, Seung Hyeok; Kang, Shin-Wook; Yoo, Tae-Hyun

    2016-02-01

    Mitochondrial dysfunction may play an important role in abnormal glucose metabolism and systemic inflammation. We aimed to investigate the relationship between mitochondrial DNA (mtDNA) copy number and clinical outcomes in peritoneal dialysis (PD) patients. We recruited 120 prevalent PD patients and determined mtDNA copy number by PCR. Primary outcome was all-cause mortality, whereas secondary outcomes included cardiovascular events, technical PD failure, and incident malignancy. Cox proportional hazards analysis determined the independent association of mtDNA copy number with outcomes. The mean patient age was 52.3 years; 42.5% were men. The mean log mtDNA copy number was 3.30 ± 0.50. During a follow-up period of 35.4 ± 19.3 months, all-cause mortality and secondary outcomes were observed in 20.0% and 59.2% of patients, respectively. Secondary outcomes were significantly lower in the highest mtDNA copy number group than in the lower groups. In multiple Cox analysis, the mtDNA copy number was not associated with all-cause mortality (lower two vs highest tertile: hazard ratio [HR] = 1.208, 95% confidence interval [CI] = 0.477-3.061). However, the highest tertile group was significantly associated with lower incidences of secondary outcomes (lower two vs highest tertile: HR [95% CI] = 0.494 [0.277-0.882]) after adjusting for confounding factors. The decreased mtDNA copy number was significantly associated with adverse clinical outcomes in PD patients. PMID:26886611

  20. Low Mitochondrial DNA Copy Number is Associated With Adverse Clinical Outcomes in Peritoneal Dialysis Patients

    PubMed Central

    Yoon, Chang-Yun; Park, Jung Tak; Kee, Youn Kyung; Han, Seung Gyu; Han, In Mee; Kwon, Young Eun; Park, Kyoung Sook; Lee, Mi Jung; Han, Seung Hyeok; Kang, Shin-Wook; Yoo, Tae-Hyun

    2016-01-01

    Abstract Mitochondrial dysfunction may play an important role in abnormal glucose metabolism and systemic inflammation. We aimed to investigate the relationship between mitochondrial DNA (mtDNA) copy number and clinical outcomes in peritoneal dialysis (PD) patients. We recruited 120 prevalent PD patients and determined mtDNA copy number by PCR. Primary outcome was all-cause mortality, whereas secondary outcomes included cardiovascular events, technical PD failure, and incident malignancy. Cox proportional hazards analysis determined the independent association of mtDNA copy number with outcomes. The mean patient age was 52.3 years; 42.5% were men. The mean log mtDNA copy number was 3.30 ± 0.50. During a follow-up period of 35.4 ± 19.3 months, all-cause mortality and secondary outcomes were observed in 20.0% and 59.2% of patients, respectively. Secondary outcomes were significantly lower in the highest mtDNA copy number group than in the lower groups. In multiple Cox analysis, the mtDNA copy number was not associated with all-cause mortality (lower two vs highest tertile: hazard ratio [HR] = 1.208, 95% confidence interval [CI] = 0.477–3.061). However, the highest tertile group was significantly associated with lower incidences of secondary outcomes (lower two vs highest tertile: HR [95% CI] = 0.494 [0.277–0.882]) after adjusting for confounding factors. The decreased mtDNA copy number was significantly associated with adverse clinical outcomes in PD patients. PMID:26886611

  1. Frequency distribution histograms for the rapid analysis of data

    NASA Technical Reports Server (NTRS)

    Burke, P. V.; Bullen, B. L.; Poff, K. L.

    1988-01-01

    The mean and standard error are good representations for the response of a population to an experimental parameter and are frequently used for this purpose. Frequency distribution histograms show, in addition, responses of individuals in the population. Both the statistics and a visual display of the distribution of the responses can be obtained easily using a microcomputer and available programs. The type of distribution shown by the histogram may suggest different mechanisms to be tested.

  2. Bin recycling strategy for improving the histogram precision on GPU

    NASA Astrophysics Data System (ADS)

    Cárdenas-Montes, Miguel; Rodríguez-Vázquez, Juan José; Vega-Rodríguez, Miguel A.

    2016-07-01

    Histogram is an easily comprehensible way to present data and analyses. In the current scientific context with access to large volumes of data, the processing time for building histogram has dramatically increased. For this reason, parallel construction is necessary to alleviate the impact of the processing time in the analysis activities. In this scenario, GPU computing is becoming widely used for reducing until affordable levels the processing time of histogram construction. Associated to the increment of the processing time, the implementations are stressed on the bin-count accuracy. Accuracy aspects due to the particularities of the implementations are not usually taken into consideration when building histogram with very large data sets. In this work, a bin recycling strategy to create an accuracy-aware implementation for building histogram on GPU is presented. In order to evaluate the approach, this strategy was applied to the computation of the three-point angular correlation function, which is a relevant function in Cosmology for the study of the Large Scale Structure of Universe. As a consequence of the study a high-accuracy implementation for histogram construction on GPU is proposed.

  3. Serum DNA Motifs Predict Disease and Clinical Status in Multiple Sclerosis

    PubMed Central

    Beck, Julia; Urnovitz, Howard B.; Saresella, Marina; Caputo, Domenico; Clerici, Mario; Mitchell, William M.; Schütz, Ekkehard

    2010-01-01

    Using recently available mass sequencing and assembly technologies, we have been able to identify and quantify unique cell-free DNA motifs in the blood of patients with multiple sclerosis (MS). The most common MS clinical syndrome, relapsing-remitting MS (RRMS), is accompanied by a unique fingerprint of both inter- and intragenic cell-free circulating nucleic acids as specific DNA sequences that provide significant clinical sensitivity and specificity. Coding genes that are differentially represented in MS serum encode cytoskeletal proteins, brain-expressed regulators of growth, and receptors involved in nervous system signal transduction. Although coding genes distinguish RRMS and its clinical activity, several repeat sequences, such as the L1M family of LINE elements, are consistently different in all MS patients and clinical status versus the normal database. These data demonstrate that DNA motifs observed in serum are characteristic of RRMS and disease activity and are promising as a clinical tool in monitoring patient responses to treatment modalities. PMID:20228264

  4. Multiple factors affect immunogenicity of DNA plasmid HIV vaccines in human clinical trials

    PubMed Central

    Jin, Xia; Morgan, Cecilia; Yu, Xuesong; DeRosa, Stephen; Tomaras, Georgia D.; Montefiori, David C.; Kublin, James; Corey, Larry; Keefer, Michael C.

    2015-01-01

    Plasmid DNA vaccines have been licensed for use in domesticated animals because of their excellent immunogenicity, but none have yet been licensed for use in humans. Here we report a retrospective analysis of 1218 healthy human volunteers enrolled in 10 phase I clinical trials in which DNA plasmids encoding HIV antigens were administered. Elicited T-cell immune responses were quantified by validated intracellular cytokine staining (ICS) stimulated with HIV peptide pools. HIV-specific binding and neutralizing antibody activities were also analyzed using validated assays. Results showed that, in the absence of adjuvants and boosting with alternative vaccines, DNA vaccines elicited CD8+ and CD4+ T-cell responses in an average of 13.3% (95% CI: 9.8% to 17.8%) and 37.7% (95% CI: 31.9% to 43.8%) of vaccine recipients, respectively. Three vaccinations (versus 2) improved the proportion of subjects with antigen-specific CD8+ responses (p=0.02), as did increased DNA dosage (p=0.007). Furthermore, female gender and participants having a lower Body Mass Index were independently associated with higher CD4+ T-cell response rate (p=0.001 and p=0.008, respectively). These vaccines elicited minimal neutralizing and binding antibody responses. These findings of the immunogenicity of HIV DNA vaccines in humans can provide guidance for future clinical trials. PMID:25820067

  5. Clinical Comparison of QUANTA Flash dsDNA Chemiluminescent Immunoassay with Four Current Assays for the Detection of Anti-dsDNA Autoantibodies

    PubMed Central

    Infantino, Maria; Meacci, Francesca; Bentow, Chelsea; Martis, Peter; Benucci, Maurizio; Afeltra, Antonella; Rigon, Amelia; Atzeni, Fabiola; Sarzi-Puttini, Piercarlo; Manfredi, Mariangela; Mahler, Michael

    2015-01-01

    Introduction. The objective of the present study was to compare QUANTA Flash dsDNA, a chemiluminescent immunoassay (CIA) on the BIO-FLASH, a rapid-response chemiluminescent analyzer, to three other anti-dsDNA antibody assays and to Crithidia luciliae indirect immunofluorescence test (CLIFT). Methods. In the first part of the study, 161 samples, 61 from patients suffering from systemic lupus erythematosus (SLE) and 100 from a disease control group, were tested by QUANTA Flash dsDNA CIA, QUANTA Lite dsDNA SC ELISA, BioPlex 2200 multiplex flow immunoassay (MFI), ImmuLisa dsDNA ELISA, and NOVA Lite CLIFT. A second cohort of 69 SLE patients was then tested by QUANTA Flash dsDNA and CLIFT to expand the study. Results. The overall qualitative agreements varied between 77.0% (NOVA Lite CLIFT versus QUANTA Lite) and 89.4% (ImmuLisa versus NOVA Lite CLIFT). The clinical sensitivities for the anti-dsDNA antibody tests varied from 8.2% (NOVA Lite CLIFT) to 54.1% (QUANTA Lite), while the clinical specificities varied from 88.0% (BioPlex 2200) to 100.0% (NOVA Lite CLIFT). Good correlation was found between QUANTA Flash dsDNA and NOVA Lite CLIFT. Conclusion. Significant variations among dsDNA methods were observed. QUANTA Flash dsDNA provides a good combination of sensitivity and specificity for the diagnosis of SLE and good agreement to CLIFT. PMID:25759849

  6. Cell-free DNA screening for fetal aneuploidy as a clinical service.

    PubMed

    Cuckle, Howard; Benn, Peter; Pergament, Eugene

    2015-10-01

    Non-invasive prenatal testing (NIPT) through the analysis of cell free (cf)DNA is revolutionizing prenatal screening for fetal aneuploidy. Current methods used in clinical practice include shotgun massively parallel sequencing (s-MPS); targeted (t-MPS); and an approach that takes advantage of single nucleotide polymorphism (SNP) differences between mother and fetus. Efficacy of cfDNA testing for the common autosomal trisomies far exceeds that of conventional screening. Depending on the methodology used, reasons for discordancy between cfDNA results and fetal karyotype can include true fetal mosaicism, confined placental mosaicism, presence of a maternal karyotype abnormality, insufficient counting due to low fetal fraction, and a vanishing twin. Among the possible cfDNA strategies a Primary test has the highest performance but is expensive, while a Contingent cfDNA test can achieve high performance at a relatively low cost. Practicalities to be considered in the provision of testing include pretest counseling about the scope and accuracy of the testing, the interpretation of results when there is a low fetal fraction and follow-up studies for positive test results. The role of first trimester nuchal translucency measurement and conventional biochemical testing needs to be reassessed in the context of the use of cfDNA. PMID:25732593

  7. DNA alterations in the tumor genome and their associations with clinical outcome in prostate cancer

    PubMed Central

    Liu, Wennuan

    2016-01-01

    Although most prostate cancer (PCa) cases are not life-threatening, approximately 293 000 men worldwide die annually due to PCa. These lethal cases are thought to be caused by coordinated genomic alterations that accumulate over time. Recent genome-wide analyses of DNA from subjects with PCa have revealed most, if not all, genetic changes in both germline and PCa tumor genomes. In this article, I first review the major, somatically acquired genomic characteristics of various subtypes of PCa. I then recap key findings on the relationships between genomic alterations and clinical parameters, such as biochemical recurrence or clinical relapse, metastasis and cancer-specific mortality. Finally, I outline the need for, and challenges with, validation of recent findings in prospective studies for clinical utility. It is clearer now than ever before that the landscape of somatically acquired aberrations in PCa is highlighted by DNA copy number alterations (CNAs) and TMPRSS2-ERG fusion derived from complex rearrangements, numerous single nucleotide variations or mutations, tremendous heterogeneity, and continuously punctuated evolution. Genome-wide CNAs, PTEN loss, MYC gain in primary tumors, and TP53 loss/mutation and AR amplification/mutation in advanced metastatic PCa have consistently been associated with worse cancer prognosis. With this recently gained knowledge, it is now an opportune time to develop DNA-based tests that provide more accurate patient stratification for prediction of clinical outcome, which will ultimately lead to more personalized cancer care than is possible at present. PMID:26975494

  8. DNA alterations in the tumor genome and their associations with clinical outcome in prostate cancer.

    PubMed

    Liu, Wennuan

    2016-01-01

    Although most prostate cancer (PCa) cases are not life-threatening, approximately 293 000 men worldwide die annually due to PCa. These lethal cases are thought to be caused by coordinated genomic alterations that accumulate over time. Recent genome-wide analyses of DNA from subjects with PCa have revealed most, if not all, genetic changes in both germline and PCa tumor genomes. In this article, I first review the major, somatically acquired genomic characteristics of various subtypes of PCa. I then recap key findings on the relationships between genomic alterations and clinical parameters, such as biochemical recurrence or clinical relapse, metastasis and cancer-specific mortality. Finally, I outline the need for, and challenges with, validation of recent findings in prospective studies for clinical utility. It is clearer now than ever before that the landscape of somatically acquired aberrations in PCa is highlighted by DNA copy number alterations (CNAs) and TMPRSS2-ERG fusion derived from complex rearrangements, numerous single nucleotide variations or mutations, tremendous heterogeneity, and continuously punctuated evolution. Genome-wide CNAs, PTEN loss, MYC gain in primary tumors, and TP53 loss/mutation and AR amplification/mutation in advanced metastatic PCa have consistently been associated with worse cancer prognosis. With this recently gained knowledge, it is now an opportune time to develop DNA-based tests that provide more accurate patient stratification for prediction of clinical outcome, which will ultimately lead to more personalized cancer care than is possible at present. PMID:26975494

  9. Quantitative comparison of DNA methylation assays for biomarker development and clinical applications.

    PubMed

    2016-07-01

    DNA methylation patterns are altered in numerous diseases and often correlate with clinically relevant information such as disease subtypes, prognosis and drug response. With suitable assays and after validation in large cohorts, such associations can be exploited for clinical diagnostics and personalized treatment decisions. Here we describe the results of a community-wide benchmarking study comparing the performance of all widely used methods for DNA methylation analysis that are compatible with routine clinical use. We shipped 32 reference samples to 18 laboratories in seven different countries. Researchers in those laboratories collectively contributed 21 locus-specific assays for an average of 27 predefined genomic regions, as well as six global assays. We evaluated assay sensitivity on low-input samples and assessed the assays' ability to discriminate between cell types. Good agreement was observed across all tested methods, with amplicon bisulfite sequencing and bisulfite pyrosequencing showing the best all-round performance. Our technology comparison can inform the selection, optimization and use of DNA methylation assays in large-scale validation studies, biomarker development and clinical diagnostics. PMID:27347756

  10. Computer-aided diagnosis method for MRI-guided prostate biopsy within the peripheral zone using grey level histograms

    NASA Astrophysics Data System (ADS)

    Rampun, Andrik; Malcolm, Paul; Zwiggelaar, Reyer

    2015-02-01

    This paper describes a computer-aided diagnosis method for targeted prostate biopsies within the peripheral zone in T2-Weighted MRI. We subdivided the peripheral zone into four regions and compare each sub region's grey level histogram with malignant and normal histogram models, and use specific metrics to estimate the presence of abnormality. The initial evaluation based on 200 MRI slices taken from 40 different patients and we achieved 87% correct classification rate with 89% and 86% sensitivity and specificity, respectively. The main contribution of this paper is a novel approach of Computer Aided Diagnosis which is using grey level histograms analysis between sub regions. In clinical point of view, the developed method could assist clinicians to perform targeted biopsies which are better than the random ones which are currently used.

  11. Detection of Head-to-Tail DNA Sequences of Human Bocavirus in Clinical Samples

    PubMed Central

    Tillmann, Ramona Liza; Wittleben, Felix; Böhmer, Anne; Müller, Andreas; Schildgen, Oliver

    2011-01-01

    Parvoviruses are single stranded DNA viruses that replicate in a so called “rolling-hairpin” mechanism, a variant of the rolling circle replication known for bacteriophages like ϕX174. The replication intermediates of parvoviruses thus are concatemers of head-to-head or tail-to-tail structure. Surprisingly, in case of the novel human bocavirus, neither head-to-head nor tail-to-tail DNA sequences were detected in clinical isolates; in contrast head-to-tail DNA sequences were identified by PCR and sequencing. Thereby, the head-to-tail sequences were linked by a novel sequence of 54 bp of which 20 bp also occur as conserved structures of the palindromic ends of parvovirus MVC which in turn is a close relative to human bocavirus. PMID:21573237

  12. DNA damage in non-communicable diseases: A clinical and epidemiological perspective.

    PubMed

    Milic, Mirta; Frustaci, Alessandra; Del Bufalo, Alessandra; Sánchez-Alarcón, Juana; Valencia-Quintana, Rafael; Russo, Patrizia; Bonassi, Stefano

    2015-06-01

    Non-communicable diseases (NCDs) are a leading cause of death and disability, representing 63% of the total death number worldwide. A characteristic phenotype of these diseases is the accelerated aging, which is the result of phenomena such as accumulated DNA damage, telomere capping loss and subcellular irreversible/nonrepaired oxidative damage. DNA damage, mostly oxidative, plays a key role in the development of most common NCDs. The present review will gather some of the most relevant knowledge concerning the presence of DNA damage in NCDs focusing on cardiovascular diseases, diabetes, chronic obstructive pulmonary disease, and neurodegenerative disorders, and discussing a selection of papers from the most informative literature. The challenge of comorbidity and the potential offered by new systems approaches for introducing these biomarkers into the clinical decision process will be discussed. Systems Medicine platforms represent the most suitable approach to personalized medicine, enabling to identify new patterns in the pathogenesis, diagnosis and prognosis of chronic diseases. PMID:26255943

  13. Design of a Clinical Information Management System to Support DNA Analysis Laboratory Operation

    PubMed Central

    Dubay, Christopher J.; Zimmerman, David; Popovich, Bradley

    1995-01-01

    The LabDirector system has been developed at the Oregon Health Sciences University to support the operation of our clinical DNA analysis laboratory. Through an iterative design process which has spanned two years, we have produced a system that is both highly tailored to a clinical genetics production laboratory and flexible in its implementation, to support the rapid growth and change of protocols and methodologies in use in the field. The administrative aspects of the system are integrated with an enterprise schedule management system. The laboratory side of the system is driven by a protocol modeling and execution system. The close integration between these two aspects of the clinical laboratory facilitates smooth operations, and allows management to accurately measure costs and performance. The entire application has been designed and documented to provide utility to a wide range of clinical laboratory environments.

  14. Preimplantation genetic diagnosis for mitochondrial DNA disorders: ethical guidance for clinical practice

    PubMed Central

    Bredenoord, Annelien; Dondorp, Wybo; Pennings, Guido; de Die-Smulders, Christine; Smeets, Bert; de Wert, Guido

    2009-01-01

    Although morally acceptable in theory, preimplantation genetic diagnosis (PGD) for mitochondrial DNA (mtDNA) disorders raises several ethical questions in clinical practice. This paper discusses the major conditions for good clinical practice. Our starting point is that PGD for mtDNA mutations should as far as possible be embedded in a scientific research protocol. For every clinical application of PGD for mtDNA disorders, it is not only important to avoid a ‘high risk of serious harm' to the future child, but also to consider to what extent it would be possible, desirable and proportional to try to reduce the health risks and minimize harm. The first issue we discuss is oocyte sampling, which may point out whether PGD is feasible for a specific couple. The second issue is whether one blastomere represents the genetic composition of the embryo as a whole – and how this could (or should) be investigated. The third issue regards the cutoff points below which embryos are considered to be eligible for transfer. We scrutinize how to determine these cutoff points and how to use these cutoff points in clinical practice – for example, when parents ask to take more or less risks. The fourth issue regards the number of cycles that can (or should) justifiably be carried out to find the best possible embryo. Fifth, we discuss whether follow-up studies should be conducted, particularly the genetic testing of children born after IVF/PGD. Finally, we offer the main information that is required to obtain a truly informed consent. PMID:19471315

  15. DNA Priming for Seasonal Influenza Vaccine: A Phase 1b Double-Blind Randomized Clinical Trial

    PubMed Central

    Ledgerwood, Julie E.; Bellamy, Abbie R.; Belshe, Robert; Bernstein, David I.; Edupuganti, Srilatha; Patel, Shital M.; Renehan, Phyllis; Zajdowicz, Thad; Schwartz, Richard; Koup, Richard; Bailer, Robert T.; Yamshchikov, Galina V.; Enama, Mary E.; Sarwar, Uzma; Larkin, Brenda; Graham, Barney S.

    2015-01-01

    Background The efficacy of current influenza vaccines is limited in vulnerable populations. DNA vaccines can be produced rapidly, and may offer a potential strategy to improve vaccine immunogenicity, indicated by studies with H5 influenza DNA vaccine prime followed by inactivated vaccine boost. Methods Four sites enrolled healthy adults, randomized to receive 2011/12 seasonal influenza DNA vaccine prime (n=65) or phosphate buffered saline (PBS) (n=66) administered intramuscularly with Biojector. All subjects received the 2012/13 seasonal inactivated influenza vaccine, trivalent (IIV3) 36 weeks after the priming injection. Vaccine safety and tolerability was the primary objective and measurement of antibody response by hemagglutination inhibition (HAI) was the secondary objective. Results The DNA vaccine prime-IIV3 boost regimen was safe and well tolerated. Significant differences in HAI responses between the DNA vaccine prime and the PBS prime groups were not detected in this study. Conclusion While DNA priming significantly improved the response to a conventional monovalent H5 vaccine in a previous study, it was not effective in adults using seasonal influenza strains, possibly due to pre-existing immunity to the prime, unmatched prime and boost antigens, or the lengthy 36 week boost interval. Careful optimization of the DNA prime-IIV3 boost regimen as related to antigen matching, interval between vaccinations, and pre-existing immune responses to influenza is likely to be needed in further evaluations of this vaccine strategy. In particular, testing this concept in younger age groups with less prior exposure to seasonal influenza strains may be informative. Trial Registration ClinicalTrials.gov NCT01498718 PMID:25950433

  16. Total HIV-1 DNA, a Marker of Viral Reservoir Dynamics with Clinical Implications.

    PubMed

    Avettand-Fènoël, Véronique; Hocqueloux, Laurent; Ghosn, Jade; Cheret, Antoine; Frange, Pierre; Melard, Adeline; Viard, Jean-Paul; Rouzioux, Christine

    2016-10-01

    HIV-1 DNA persists in infected cells despite combined antiretroviral therapy (cART), forming viral reservoirs. Recent trials of strategies targeting latent HIV reservoirs have rekindled hopes of curing HIV infection, and reliable markers are thus needed to evaluate viral reservoirs. Total HIV DNA quantification is simple, standardized, sensitive, and reproducible. Total HIV DNA load influences the course of the infection and is therefore clinically relevant. In particular, it is predictive of progression to AIDS and death, independently of HIV RNA load and the CD4 cell count. Baseline total HIV DNA load is predictive of the response to cART. It declines during cART but remains quantifiable, at a level that reflects both the history of infection (HIV RNA zenith, CD4 cell count nadir) and treatment efficacy (residual viremia, cumulative viremia, immune restoration, immune cell activation). Total HIV DNA load in blood is also predictive of the presence and severity of some HIV-1-associated end-organ disorders. It can be useful to guide individual treatment, notably, therapeutic de-escalation. Although it does not distinguish between replication-competent and -defective latent viruses, the total HIV DNA load in blood, tissues, and cells provides insights into HIV pathogenesis, probably because all viral forms participate in host cell activation and HIV pathogenesis. Total HIV DNA is thus a biomarker of HIV reservoirs, which can be defined as all infected cells and tissues containing all forms of HIV persistence that participate in pathogenesis. This participation may occur through the production of new virions, creating new cycles of infection and disseminating infected cells; maintenance or amplification of reservoirs by homeostatic cell proliferation; and viral transcription and synthesis of viral proteins without new virion production. These proteins can induce immune activation, thus participating in the vicious circle of HIV pathogenesis. PMID:27559075

  17. Face recognition with histograms of fractional differential gradients

    NASA Astrophysics Data System (ADS)

    Yu, Lei; Ma, Yan; Cao, Qi

    2014-05-01

    It has proved that fractional differentiation can enhance the edge information and nonlinearly preserve textural detailed information in an image. This paper investigates its ability for face recognition and presents a local descriptor called histograms of fractional differential gradients (HFDG) to extract facial visual features. HFDG encodes a face image into gradient patterns using multiorientation fractional differential masks, from which histograms of gradient directions are computed as the face representation. Experimental results on Yale, face recognition technology (FERET), Carnegie Mellon University pose, illumination, and expression (CMU PIE), and A. Martinez and R. Benavente (AR) databases validate the feasibility of the proposed method and show that HFDG outperforms local binary patterns (LBP), histograms of oriented gradients (HOG), enhanced local directional patterns (ELDP), and Gabor feature-based methods.

  18. Java multi-histogram volume rendering framework for medical images

    NASA Astrophysics Data System (ADS)

    Senseney, Justin; Bokinsky, Alexandra; Cheng, Ruida; McCreedy, Evan; McAuliffe, Matthew J.

    2013-03-01

    This work extends the multi-histogram volume rendering framework proposed by Kniss et al. [1] to provide rendering results based on the impression of overlaid triangles on a graph of image intensity versus gradient magnitude. The developed method of volume rendering allows for greater emphasis to boundary visualization while avoiding issues common in medical image acquisition. For example, partial voluming effects in computed tomography and intensity inhomogeneity of similar tissue types in magnetic resonance imaging introduce pixel values that will not reflect differing tissue types when a standard transfer function is applied to an intensity histogram. This new framework uses developing technology to improve upon the Kniss multi-histogram framework by using Java, the GPU, and MIPAV, an open-source medical image processing application, to allow multi-histogram techniques to be widely disseminated. The OpenGL view aligned texture rendering approach suffered from performance setbacks, inaccessibility, and usability problems. Rendering results can now be interactively compared with other rendering frameworks, surfaces can now be extracted for use in other programs, and file formats that are widely used in the field of biomedical imaging can be visualized using this multi-histogram approach. OpenCL and GLSL are used to produce this new multi-histogram approach, leveraging texture memory on the graphics processing unit of desktops to provide a new interactive method for visualizing biomedical images. Performance results for this method are generated and qualitative rendering results are compared. The resulting framework provides the opportunity for further applications in medical imaging, both in volume rendering and in generic image processing.

  19. Circulating Tumor Cells (CTC) and Cell-Free DNA (cfDNA) Workshop 2016: Scientific Opportunities and Logistics for Cancer Clinical Trial Incorporation.

    PubMed

    Lowes, Lori E; Bratman, Scott V; Dittamore, Ryan; Done, Susan; Kelley, Shana O; Mai, Sabine; Morin, Ryan D; Wyatt, Alexander W; Allan, Alison L

    2016-01-01

    Despite the identification of circulating tumor cells (CTCs) and cell-free DNA (cfDNA) as potential blood-based biomarkers capable of providing prognostic and predictive information in cancer, they have not been incorporated into routine clinical practice. This resistance is due in part to technological limitations hampering CTC and cfDNA analysis, as well as a limited understanding of precisely how to interpret emergent biomarkers across various disease stages and tumor types. In recognition of these challenges, a group of researchers and clinicians focused on blood-based biomarker development met at the Canadian Cancer Trials Group (CCTG) Spring Meeting in Toronto, Canada on 29 April 2016 for a workshop discussing novel CTC/cfDNA technologies, interpretation of data obtained from CTCs versus cfDNA, challenges regarding disease evolution and heterogeneity, and logistical considerations for incorporation of CTCs/cfDNA into clinical trials, and ultimately into routine clinical use. The objectives of this workshop included discussion of the current barriers to clinical implementation and recent progress made in the field, as well as fueling meaningful collaborations and partnerships between researchers and clinicians. We anticipate that the considerations highlighted at this workshop will lead to advances in both basic and translational research and will ultimately impact patient management strategies and patient outcomes. PMID:27618023

  20. Molecular determination of RhD phenotype by DNA typing: clinical applications.

    PubMed

    Cotorruelo, C; Biondi, C; Borrás, S G; Galizzi, S; Di Mónaco, R; Racca, A

    2000-11-01

    Rhesus D (RhD) typing is performed by agglutination methods; however, in clinical situations where these techniques cannot be performed, RhD DNA typing is an alternative approach. The Rh antigens are encoded by the RHD and RHCE genes. In RhD-negative individuals the RHD gene is absent or grossly deleted, but variations in the arrangement of the RH locus in different populations are emerging. The aim of this study was to analyse the gross organization of the RH genes in our population using a previously described multiplex polymerase chain reaction (PCR) method with some modifications. We studied 253 DNA samples from Argentinian blood donors, 15 samples with a reduced expression of the D antigen and 1 Dc- phenotype. We evaluated the clinical utility of this method to ascertain the RhD antigen in 10 patients with warm-type autoimmune haemolytic anaemia (AIHA) and 14 samples of amniotic fluids. All Rh phenotypes were properly characterized and no discrepancies with serological typing were found. Analyses performed in the Dc- phenotype suggest the presence of a hybrid RHCE-RHD gene. DNA typing confirmed the RhD-negative type of one AIHA sample in which serological tests were inconclusive. Foetal DNA typing correctly indicated the RhD in every foetus. VNTR (variable number of tandem repeats) and STR (short tandem repeats) analysis detected maternal contamination in two amniocentesis samples and confirmed the foetal origin of 12. This multiplex PCR strategy is suitable for RhD determination in clinical situations in which serological typing cannot be accomplished with its usual ease. PMID:11085623

  1. DNA fingerprinting and electrophoretic karyotype of environmental and clinical isolates of Candida parapsilosis.

    PubMed Central

    Carruba, G; Pontieri, E; De Bernardis, F; Martino, P; Cassone, A

    1991-01-01

    The endonuclease restriction pattern (DNA fingerprinting) and the electrophoretic karyotype of 16 Candida parapsilosis isolates from environmental and clinical sources were investigated. DNA from both whole cells and separated mitochondria was digested with enzymes, including EcoRI, BamHI, KpnI, BglII, HpaII, PvuII, and HindIII. Regardless of their source and pathogenic properties, all isolates showed a uniform, reproducible, and overlapping whole-cell DNA fingerprinting with each endonuclease digest. Mitochondrial DNA fragments were, in all cases, major contributors to the total cellular DNA restriction pattern. In contrast, the electrophoretic karyotype generated by rotating field gel electrophoresis (RFGE) or contour clamped homogeneous field electrophoresis (CHEF) showed a remarkable polymorphism among the isolates. This polymorphism concerned the smaller molecular size section of the karyotype (range, 1.8 to 0.7 Mb), where at least two to five chromosomal bands could be consistently detected by both RFGE and CHEF. Larger (greater than or equal to 3.0 to 1.9 Mb) chromosome-sized DNA bands (four in CHEF and three in RFGE) were quite distinct and common to all isolates. Thus, seven karyotype classes could be defined, on the basis of both the number and size of putative chromosomes. The three categories of isolates (soil, vaginal, and hematological) were not randomly distributed among the seven classes. In particular, the four hematological isolates had a karyotype pattern which was clearly distinct from that shown by the three environmental isolates, and of the nine vaginal isolates only one shared a class with isolates from another source (soil). Although tentative, the classification was totally consistent with the independent and reproducible results obtained by the two pulse-field electrophoretic techniques employed. It is suggested that the electrophoretic analysis of the karyotype might be particularly useful for epidemiological and pathogenicity studies on

  2. Is mitochondrial DNA copy number associated with clinical characteristics and prognosis in gastric cancer?

    PubMed

    Lee, Hyunsu; Lee, Jae-Ho; Kim, Dong-Choon; Hwang, IlSeon; Kang, Yu-Na; Gwon, Gi-Jeong; Choi, In-Jang; Kim, Shin

    2015-01-01

    Alterations in mitochondrial DNA (mtDNA) have been studied in various cancers. However, the clinical value of mtDNA copy number (mtCN) alterations in gastric cancer (GC) is poorly understood. In the present study, we investigated whether alterations in mtCNs might be associated with clinicopathological parameters in GC cases. mtCN was measured in 109 patients with GC by quantitative real-time PCR. Then, correlations with clinicopathological characteristics were analyzed. mtCN was elevated in 64.2% of GC tissues compared with paired, adjacent, non-cancerous tissue. However, the observed alterations in mtCN were not associated with any clinicopathological characteristics, including age, gender, TN stage, Lauren classification, lymph node metastasis, and depth of invasion. Moreover, Kaplan-Meier survival curves revealed that mtCN was not significantly associated with the survival of GC patients. In this study, we demonstrated that mtCN was not a significant marker for predicting clinical characteristics or prognosis in GC. PMID:25640396

  3. Reprint of "The clinical impact of deficiency in DNA non-homologous end-joining".

    PubMed

    Woodbine, Lisa; Gennery, Andrew R; Jeggo, Penny A

    2014-05-01

    DNA non-homologous end-joining (NHEJ) is the major DNA double strand break (DSB) repair pathway in mammalian cells. Defects in NHEJ proteins confer marked radiosensitivity in cell lines and mice models, since radiation potently induces DSBs. The process of V(D)J recombination functions during the development of the immune response, and involves the introduction and rejoining of programmed DSBs to generate an array of diverse T and B cells. NHEJ rejoins these programmed DSBs. Consequently, NHEJ deficiency confers (severe) combined immunodeficiency - (S)CID - due to a failure to carry out V(D)J recombination efficiently. NHEJ also functions in class switch recombination, another step enhancing T and B cell diversity. Prompted by these findings, a search for radiosensitivity amongst (S)CID patients revealed a radiosensitive sub-class, defined as RS-SCID. Mutations in NHEJ genes, defining human syndromes deficient in DNA ligase IV (LIG4 Syndrome), XLF-Cernunnos, Artemis or DNA-PKcs, have been identified in such patients. Mutations in XRCC4 or Ku70,80 in patients have not been identified. RS-SCID patients frequently display additional characteristics including microcephaly, dysmorphic facial features and growth delay. Here, we overview the clinical spectrum of RS-SCID patients and discuss our current understanding of the underlying biology. PMID:24780557

  4. The clinical impact of deficiency in DNA non-homologous end-joining.

    PubMed

    Woodbine, Lisa; Gennery, Andrew R; Jeggo, Penny A

    2014-04-01

    DNA non-homologous end-joining (NHEJ) is the major DNA double strand break (DSB) repair pathway in mammalian cells. Defects in NHEJ proteins confer marked radiosensitivity in cell lines and mice models, since radiation potently induces DSBs. The process of V(D)J recombination functions during the development of the immune response, and involves the introduction and rejoining of programmed DSBs to generate an array of diverse T and B cells. NHEJ rejoins these programmed DSBs. Consequently, NHEJ deficiency confers (severe) combined immunodeficiency - (S)CID - due to a failure to carry out V(D)J recombination efficiently. NHEJ also functions in class switch recombination, another step enhancing T and B cell diversity. Prompted by these findings, a search for radiosensitivity amongst (S)CID patients revealed a radiosensitive sub-class, defined as RS-SCID. Mutations in NHEJ genes, defining human syndromes deficient in DNA ligase IV (LIG4 Syndrome), XLF-Cernunnos, Artemis or DNA-PKcs, have been identified in such patients. Mutations in XRCC4 or Ku70,80 in patients have not been identified. RS-SCID patients frequently display additional characteristics including microcephaly, dysmorphic facial features and growth delay. Here, we overview the clinical spectrum of RS-SCID patients and discuss our current understanding of the underlying biology. PMID:24629483

  5. On algorithmic optimization of histogramming functions for GEM systems

    NASA Astrophysics Data System (ADS)

    Krawczyk, Rafał D.; Czarski, Tomasz; Kolasinski, Piotr; Poźniak, Krzysztof T.; Linczuk, Maciej; Byszuk, Adrian; Chernyshova, Maryna; Juszczyk, Bartlomiej; Kasprowicz, Grzegorz; Wojenski, Andrzej; Zabolotny, Wojciech

    2015-09-01

    This article concerns optimization methods for data analysis for the X-ray GEM detector system. The offline analysis of collected samples was optimized for MATLAB computations. Compiled functions in C language were used with MEX library. Significant speedup was received for both ordering-preprocessing and for histogramming of samples. Utilized techniques with obtained results are presented.

  6. Histogram-Based Calibration Method for Pipeline ADCs.

    PubMed

    Son, Hyeonuk; Jang, Jaewon; Kim, Heetae; Kang, Sungho

    2015-01-01

    Measurement and calibration of an analog-to-digital converter (ADC) using a histogram-based method requires a large volume of data and a long test duration, especially for a high resolution ADC. A fast and accurate calibration method for pipelined ADCs is proposed in this research. The proposed calibration method composes histograms through the outputs of each stage and calculates error sources. The digitized outputs of a stage are influenced directly by the operation of the prior stage, so the results of the histogram provide the information of errors in the prior stage. The composed histograms reduce the required samples and thus calibration time being implemented by simple modules. For 14-bit resolution pipelined ADC, the measured maximum integral non-linearity (INL) is improved from 6.78 to 0.52 LSB, and the spurious-free dynamic range (SFDR) and signal-to-noise-and-distortion ratio (SNDR) are improved from 67.0 to 106.2dB and from 65.6 to 84.8dB, respectively. PMID:26070196

  7. Tumor DNA in cerebral spinal fluid reflects clinical course in a patient with melanoma leptomeningeal brain metastases.

    PubMed

    Li, Yingmei; Pan, Wenying; Connolly, Ian D; Reddy, Sunil; Nagpal, Seema; Quake, Stephen; Gephart, Melanie Hayden

    2016-05-01

    Cerebral spinal fluid (CSF) from brain tumor patients contains tumor cellular and cell-free DNA (cfDNA), which provides a less-invasive and routinely accessible method to obtain tumor genomic information. In this report, we used droplet digital PCR to test mutant tumor DNA in CSF of a patient to monitor the treatment response of metastatic melanoma leptomeningeal disease (LMD). The primary melanoma was known to have a BRAF (V600E) mutation, and the patient was treated with whole brain radiotherapy and BRAF inhibitors. We collected 9 CSF samples over 6 months. The mutant cfDNA fraction gradually decreased from 53 % (time of diagnosis) to 0 (time of symptom alleviation) over the first 6 time points. Three months after clinical improvement, the patient returned with severe symptoms and the mutant cfDNA was again detected in CSF at high levels. The mutant DNA fraction corresponded well with the patient's clinical response. We used whole exome sequencing to examine the mutation profiles of the LMD tumor DNA in CSF before therapeutic response and after disease relapse, and discovered a canonical cancer mutation PTEN (R130*) at both time points. The cellular and cfDNA revealed similar mutation profiles, suggesting cfDNA is representative of LMD cells. This study demonstrates the potential of using cellular or cfDNA in CSF to monitor treatment response for LMD. PMID:26961773

  8. Clinical Significance of a Point Mutation in DNA Polymerase Beta (POLB) Gene in Gastric Cancer

    PubMed Central

    Tan, Xiaohui; Wang, Hongyi; Luo, Guangbin; Ren, Shuyang; Li, Wenmei; Cui, Jiantao; Gill, Harindarpal S.; Fu, Sidney W.; Lu, Youyong

    2015-01-01

    Gastric cancer (GC) is a major cause of global cancer mortality. Genetic variations in DNA repair genes can modulate DNA repair capability and, consequently, have been associated with risk of developing cancer. We have previously identified a T to C point mutation at nucleotide 889 (T889C) in DNA polymerase beta (POLB) gene, a key enzyme involved in base excision repair in primary GCs. The purpose of this study was to evaluate the mutation and expression of POLB in a larger cohort and to identify possible prognostic roles of the POLB alterations in GC. Primary GC specimens and their matched normal adjacent tissues were collected at the time of surgery. DNA, RNA and protein samples were isolated from GC specimens and cell lines. Mutations were detected by PCR-RFLP/DHPLC and sequencing analysis. POLB gene expression was examined by RT-PCR, tissue microarray, Western blotting and immunofluorescence assays. The function of the mutation was evaluated by chemosensitivity, MTT, Transwell matrigel invasion and host cell reactivation assays. The T889C mutation was detected in 18 (10.17%) of 177 GC patients. And the T889C mutation was associated with POLB overexpression, lymph nodes metastases and poor tumor differentiation. In addition, patients with- the mutation had significantly shorter survival time than those without-, following postoperative chemotherapy. Furthermore, cell lines with T889C mutation in POLB gene were more resistant to the treatment of 5-fluorouracil, cisplatin and epirubicin than those with wild type POLB. Forced expression of POLB gene with T889C mutation resulted in enhanced cell proliferation, invasion and resistance to anticancer drugs, along with increased DNA repair capability. These results suggest that POLB gene with T889C mutation in surgically resected primary gastric tissues may be clinically useful for predicting responsiveness to chemotherapy in patients with GC. The POLB gene alteration may serve as a prognostic biomarker for GC. PMID

  9. Decoding brain cancer dynamics: a quantitative histogram-based approach using temporal MRI

    NASA Astrophysics Data System (ADS)

    Zhou, Mu; Hall, Lawrence O.; Goldgof, Dmitry B.; Russo, Robin; Gillies, Robert J.; Gatenby, Robert A.

    2015-03-01

    Brain tumor heterogeneity remains a challenge for probing brain cancer evolutionary dynamics. In light of evolution, it is a priority to inspect the cancer system from a time-domain perspective since it explicitly tracks the dynamics of cancer variations. In this paper, we study the problem of exploring brain tumor heterogeneity from temporal clinical magnetic resonance imaging (MRI) data. Our goal is to discover evidence-based knowledge from such temporal imaging data, where multiple clinical MRI scans from Glioblastoma multiforme (GBM) patients are generated during therapy. In particular, we propose a quantitative histogram-based approach that builds a prediction model to measure the difference in histograms obtained from pre- and post-treatment. The study could significantly assist radiologists by providing a metric to identify distinctive patterns within each tumor, which is crucial for the goal of providing patient-specific treatments. We examine the proposed approach for a practical application - clinical survival group prediction. Experimental results show that our approach achieved 90.91% accuracy.

  10. DNA Aptamer Selected against Pancreatic Ductal Adenocarcinoma for in vivo Imaging and Clinical Tissue Recognition

    PubMed Central

    Wu, Xiaoqiu; Zhao, Zilong; Bai, Huarong; Fu, Ting; Yang, Chao; Hu, Xiaoxiao; Liu, Qiaoling; Champanhac, Carole; Teng, I-Ting; Ye, Mao; Tan, Weihong

    2015-01-01

    In this work, we have developed a truncated DNA aptamer, termed XQ-2d, with high affinity and specificity for pancreatic ductal adenocarcinoma (PDAC). Aptamer XQ-2d selectively binds to PL45 cells with a dissociation constant in the nanomolar range, as determined by its recognition of PL45 tumor cells in mice. Moreover, XQ-2d shows better recognition ratio for 40 tissue sections of clinical PDAC samples (82.5%) compared to the initial cell-SELEX selection library (5%). Therefore, XQ-2d can be considered a promising candidate as a tool for PDAC diagnosis and treatment. PMID:26155314

  11. DNA Aptamer Selected against Pancreatic Ductal Adenocarcinoma for in vivo Imaging and Clinical Tissue Recognition.

    PubMed

    Wu, Xiaoqiu; Zhao, Zilong; Bai, Huarong; Fu, Ting; Yang, Chao; Hu, Xiaoxiao; Liu, Qiaoling; Champanhac, Carole; Teng, I-Ting; Ye, Mao; Tan, Weihong

    2015-01-01

    In this work, we have developed a truncated DNA aptamer, termed XQ-2d, with high affinity and specificity for pancreatic ductal adenocarcinoma (PDAC). Aptamer XQ-2d selectively binds to PL45 cells with a dissociation constant in the nanomolar range, as determined by its recognition of PL45 tumor cells in mice. Moreover, XQ-2d shows better recognition ratio for 40 tissue sections of clinical PDAC samples (82.5%) compared to the initial cell-SELEX selection library (5%). Therefore, XQ-2d can be considered a promising candidate as a tool for PDAC diagnosis and treatment. PMID:26155314

  12. Exome Sequencing of Cell-Free DNA from Metastatic Cancer Patients Identifies Clinically Actionable Mutations Distinct from Primary Disease.

    PubMed

    Butler, Timothy M; Johnson-Camacho, Katherine; Peto, Myron; Wang, Nicholas J; Macey, Tara A; Korkola, James E; Koppie, Theresa M; Corless, Christopher L; Gray, Joe W; Spellman, Paul T

    2015-01-01

    The identification of the molecular drivers of cancer by sequencing is the backbone of precision medicine and the basis of personalized therapy; however, biopsies of primary tumors provide only a snapshot of the evolution of the disease and may miss potential therapeutic targets, especially in the metastatic setting. A liquid biopsy, in the form of cell-free DNA (cfDNA) sequencing, has the potential to capture the inter- and intra-tumoral heterogeneity present in metastatic disease, and, through serial blood draws, track the evolution of the tumor genome. In order to determine the clinical utility of cfDNA sequencing we performed whole-exome sequencing on cfDNA and tumor DNA from two patients with metastatic disease; only minor modifications to our sequencing and analysis pipelines were required for sequencing and mutation calling of cfDNA. The first patient had metastatic sarcoma and 47 of 48 mutations present in the primary tumor were also found in the cell-free DNA. The second patient had metastatic breast cancer and sequencing identified an ESR1 mutation in the cfDNA and metastatic site, but not in the primary tumor. This likely explains tumor progression on Anastrozole. Significant heterogeneity between the primary and metastatic tumors, with cfDNA reflecting the metastases, suggested separation from the primary lesion early in tumor evolution. This is best illustrated by an activating PIK3CA mutation (H1047R) which was clonal in the primary tumor, but completely absent from either the metastasis or cfDNA. Here we show that cfDNA sequencing supplies clinically actionable information with minimal risks compared to metastatic biopsies. This study demonstrates the utility of whole-exome sequencing of cell-free DNA from patients with metastatic disease. cfDNA sequencing identified an ESR1 mutation, potentially explaining a patient's resistance to aromatase inhibition, and gave insight into how metastatic lesions differ from the primary tumor. PMID:26317216

  13. Exome Sequencing of Cell-Free DNA from Metastatic Cancer Patients Identifies Clinically Actionable Mutations Distinct from Primary Disease

    PubMed Central

    Butler, Timothy M.; Johnson-Camacho, Katherine; Peto, Myron; Wang, Nicholas J.; Macey, Tara A.; Korkola, James E.; Koppie, Theresa M.; Corless, Christopher L.; Gray, Joe W.; Spellman, Paul T.

    2015-01-01

    The identification of the molecular drivers of cancer by sequencing is the backbone of precision medicine and the basis of personalized therapy; however, biopsies of primary tumors provide only a snapshot of the evolution of the disease and may miss potential therapeutic targets, especially in the metastatic setting. A liquid biopsy, in the form of cell-free DNA (cfDNA) sequencing, has the potential to capture the inter- and intra-tumoral heterogeneity present in metastatic disease, and, through serial blood draws, track the evolution of the tumor genome. In order to determine the clinical utility of cfDNA sequencing we performed whole-exome sequencing on cfDNA and tumor DNA from two patients with metastatic disease; only minor modifications to our sequencing and analysis pipelines were required for sequencing and mutation calling of cfDNA. The first patient had metastatic sarcoma and 47 of 48 mutations present in the primary tumor were also found in the cell-free DNA. The second patient had metastatic breast cancer and sequencing identified an ESR1 mutation in the cfDNA and metastatic site, but not in the primary tumor. This likely explains tumor progression on Anastrozole. Significant heterogeneity between the primary and metastatic tumors, with cfDNA reflecting the metastases, suggested separation from the primary lesion early in tumor evolution. This is best illustrated by an activating PIK3CA mutation (H1047R) which was clonal in the primary tumor, but completely absent from either the metastasis or cfDNA. Here we show that cfDNA sequencing supplies clinically actionable information with minimal risks compared to metastatic biopsies. This study demonstrates the utility of whole-exome sequencing of cell-free DNA from patients with metastatic disease. cfDNA sequencing identified an ESR1 mutation, potentially explaining a patient’s resistance to aromatase inhibition, and gave insight into how metastatic lesions differ from the primary tumor. PMID:26317216

  14. Depletion of Human DNA in Spiked Clinical Specimens for Improvement of Sensitivity of Pathogen Detection by Next-Generation Sequencing.

    PubMed

    Hasan, Mohammad R; Rawat, Arun; Tang, Patrick; Jithesh, Puthen V; Thomas, Eva; Tan, Rusung; Tilley, Peter

    2016-04-01

    Next-generation sequencing (NGS) technology has shown promise for the detection of human pathogens from clinical samples. However, one of the major obstacles to the use of NGS in diagnostic microbiology is the low ratio of pathogen DNA to human DNA in most clinical specimens. In this study, we aimed to develop a specimen-processing protocol to remove human DNA and enrich specimens for bacterial and viral DNA for shotgun metagenomic sequencing. Cerebrospinal fluid (CSF) and nasopharyngeal aspirate (NPA) specimens, spiked with control bacterial and viral pathogens, were processed using either a commercially available kit (MolYsis) or various detergents followed by DNase prior to the extraction of DNA. Relative quantities of human DNA and pathogen DNA were determined by real-time PCR. The MolYsis kit did not improve the pathogen-to-human DNA ratio, but significant reductions (>95%;P< 0.001) in human DNA with minimal effect on pathogen DNA were achieved in samples that were treated with 0.025% saponin, a nonionic surfactant. Specimen preprocessing significantly decreased NGS reads mapped to the human genome (P< 0.05) and improved the sensitivity of pathogen detection (P< 0.01), with a 20- to 650-fold increase in the ratio of microbial reads to human reads. Preprocessing also permitted the detection of pathogens that were undetectable in the unprocessed samples. Our results demonstrate a simple method for the reduction of background human DNA for metagenomic detection for a broad range of pathogens in clinical samples. PMID:26763966

  15. Wildfire Detection using by Multi Dimensional Histogram in Boreal Forest

    NASA Astrophysics Data System (ADS)

    Honda, K.; Kimura, K.; Honma, T.

    2008-12-01

    Early detection of wildfires is an issue for reduction of damage to environment and human. There are some attempts to detect wildfires by using satellite imagery, which are mainly classified into three methods: Dozier Method(1981-), Threshold Method(1986-) and Contextual Method(1994-). However, the accuracy of these methods is not enough: some commission and omission errors are included in the detected results. In addition, it is not so easy to analyze satellite imagery with high accuracy because of insufficient ground truth data. Kudoh and Hosoi (2003) developed the detection method by using three-dimensional (3D) histogram from past fire data with the NOAA-AVHRR imagery. But their method is impractical because their method depends on their handworks to pick up past fire data from huge data. Therefore, the purpose of this study is to collect fire points as hot spots efficiently from satellite imagery and to improve the method to detect wildfires with the collected data. As our method, we collect past fire data with the Alaska Fire History data obtained by the Alaska Fire Service (AFS). We select points that are expected to be wildfires, and pick up the points inside the fire area of the AFS data. Next, we make 3D histogram with the past fire data. In this study, we use Bands 1, 21 and 32 of MODIS. We calculate the likelihood to detect wildfires with the three-dimensional histogram. As our result, we select wildfires with the 3D histogram effectively. We can detect the troidally spreading wildfire. This result shows the evidence of good wildfire detection. However, the area surrounding glacier tends to rise brightness temperature. It is a false alarm. Burnt area and bare ground are sometimes indicated as false alarms, so that it is necessary to improve this method. Additionally, we are trying various combinations of MODIS bands as the better method to detect wildfire effectively. So as to adjust our method in another area, we are applying our method to tropical

  16. A clinical measure of DNA methylation predicts outcome in de novo acute myeloid leukemia

    PubMed Central

    Luskin, Marlise R.; Gimotty, Phyllis A.; Smith, Catherine; Loren, Alison W.; Figueroa, Maria E.; Harrison, Jenna; Sun, Zhuoxin; Tallman, Martin S.; Paietta, Elisabeth M.; Litzow, Mark R.; Melnick, Ari M.; Levine, Ross L.; Fernandez, Hugo F.; Luger, Selina M.; Carroll, Martin

    2016-01-01

    BACKGROUND Variable response to chemotherapy in acute myeloid leukemia (AML) represents a major treatment challenge. Clinical and genetic features incompletely predict outcome. The value of clinical epigenetic assays for risk classification has not been extensively explored. We assess the prognostic implications of a clinical assay for multilocus DNA methylation on adult patients with de novo AML. METHODS We performed multilocus DNA methylation assessment using xMELP on samples and calculated a methylation statistic (M-score) for 166 patients from UPENN with de novo AML who received induction chemotherapy. The association of M-score with complete remission (CR) and overall survival (OS) was evaluated. The optimal M-score cut-point for identifying groups with differing survival was used to define a binary M-score classifier. This classifier was validated in an independent cohort of 383 patients from the Eastern Cooperative Oncology Group Trial 1900 (E1900; NCT00049517). RESULTS A higher mean M-score was associated with death and failure to achieve CR. Multivariable analysis confirmed that a higher M-score was associated with death (P = 0.011) and failure to achieve CR (P = 0.034). Median survival was 26.6 months versus 10.6 months for low and high M-score groups. The ability of the M-score to perform as a classifier was confirmed in patients ≤ 60 years with intermediate cytogenetics and patients who achieved CR, as well as in the E1900 validation cohort. CONCLUSION The M-score represents a valid binary prognostic classifier for patients with de novo AML. The xMELP assay and associated M-score can be used for prognosis and should be further investigated for clinical decision making in AML patients. PMID:27446991

  17. The clinical utility of HPV DNA testing in cervical cancer screening strategies.

    PubMed

    Bhatla, Neerja; Moda, Nidhi

    2009-09-01

    Cervical cancer continues to be the commonest cause of death among women in developing countries, largely due to the failure to the inability to sustain effective cytology-based screening programs. While this burden may come down following implementation of the human papillomavirus (HPV) vaccine, screening will still be required. HPV DNA testing is a promising new technology for cervical cancer prevention and is the most reproducible of all cervical cancer screening tests. Presently, the two assays most widely used for the detection of genital types are the polymerase chain reaction (PCR) and Hybrid Capture 2 assays (hc2). Rapid, affordable tests are expected to be available soon. HPV DNA testing can be used in a variety of clinical scenarios that include primary screening in women older than 30 yr; as an adjunctive test to cytology; in the triage of women with an equivocal cytologic report, e.g., ASC-US; or for follow-up post-treatment for cervical intraepithelial neoplasia (CIN). HPV DNA testing can also be performed on self-collected samples, which allows screening in remote areas and also in women who refuse gynecologic examination. PMID:19901435

  18. DNA gyrase gyrA mutations in quinolone-resistant clinical isolates of Pseudomonas aeruginosa.

    PubMed Central

    Yonezawa, M; Takahata, M; Matsubara, N; Watanabe, Y; Narita, H

    1995-01-01

    The mutations in the quinolone resistance-determining region of the gyrA gene from clinical isolates of Pseudomonas aeruginosa were determined by DNA sequencing. The strains were isolated in 1989 and 1993. No mutations were detected in the clinical isolates in 1989, while five types of mutations were identified in the isolates in 1993. These mutations were as follows: group 1, a Thr residue to an Ile residue at position 83 (Thr-83-Ile); group 2, Asp-87-Asn; group 3, Thr-83-Ile and Asp-87-Gly; group 4, Thr-83-Ile and Asp-87-Asn; group 5, Thr-83-Ile and Asp-87-His. Three types of double mutations (groups 3, 4, and 5) have not been described previously. These mutations were homologous to the Ser-83-Leu, Asp-87-Asn, and Asp-87-Gly changes observed in Escherichia coli. Thus, DNA gyrase A subunit mutations are implicated in resistance to quinolones in P. aeruginosa as well as E. coli. PMID:8540700

  19. Cell-Free DNA Screening: Complexities and Challenges of Clinical Implementation.

    PubMed

    Grace, Matthew R; Hardisty, Emily; Dotters-Katz, Sarah K; Vora, Neeta L; Kuller, Jeffrey A

    2016-08-01

    Screening for fetal aneuploidy in pregnant women using cell-free DNA has increased dramatically since the technology became commercially available in 2011. Since that time, numerous trials have demonstrated high sensitivity and specificity to screen for common aneuploidies in high-risk populations. Studies assessing the performance of these tests in low-risk populations have also demonstrated improved detection rates compared with traditional, serum-based screening strategies. Concurrent with the increased use of this technology has been a decrease in invasive procedures (amniocentesis and chorionic villus sampling). As the technology becomes more widely understood, available, and utilized, challenges regarding its clinical implementation have become apparent. Some of these challenges include test failures, false-positive and false-negative results, limitations in positive predictive value in low-prevalence populations, and potential maternal health implications of abnormal results. In addition, commercial laboratories are expanding screening beyond common aneuploidies to include microdeletion screening and whole genome screening. This review article is intended to provide the practicing obstetrician with a summary of the complexities of cell-free DNA screening and the challenges of implementing it in the clinical setting. PMID:27526871

  20. Phosphorus-32, a Clinically Available Drug, Inhibits Cancer Growth by Inducing DNA Double-Strand Breakage

    PubMed Central

    Cheng, Yulan; Kiess, Ana P.; Herman, Joseph M.; Pomper, Martin G.; Meltzer, Stephen J.; Abraham, John M.

    2015-01-01

    Radioisotopes that emit electrons (beta particles), such as radioiodine, can effectively kill target cells, including cancer cells. Aqueous 32P[PO4] is a pure beta-emitter that has been used for several decades to treat non-malignant human myeloproliferative diseases. 32P[PO4] was directly compared to a more powerful pure beta-emitter, the clinically important 90Y isotope. In vitro, 32P[PO4] was more effective at killing cells than was the more powerful isotope 90Y (P ≤ 0.001) and also caused substantially more double-stranded DNA breaks than did 90Y. In vivo, a single low-dose intravenous dose of aqueous elemental 32P significantly inhibited tumor growth in the syngeneic murine cancer model (P ≤ 0.001). This effect is exerted by direct incorporation into nascent DNA chains, resulting in double-stranded breakage, a unique mechanism not duplicatable by other, more powerful electron-emitting radioisotopes. 32P[PO4] should be considered for human clinical trials as a potential novel anti-cancer drug. PMID:26030880

  1. Geographic distribution of co-dominant DNA stemlines in breast carcinoma

    SciTech Connect

    Visscher, D.; Dolan, P.; Ottosen, S.; Crissman, J.

    1995-09-01

    Breast carcinomas often contain multiple DNA stemlines in flow cytometric DNA histograms. However, due to mixing during tissue disaggregation the microanatomical relationship between the cells which comprise distinct stemlines is unclear. We performed image cytophotometric DNA analysis (IA) on two separate areas of intact tissue sections of 19 breast carcinomas which were selected on the basis of flow cytometric (FCM) DNA content heterogeneity (i.e., multiple stemlines). For comparison, similar analyses were performed on seven tumors with unimodal FCM DNA histograms. Six of the 7 tumors (86%) with unimodal FCM histograms were also unimodal in both IA DNA histograms. Among tumors with heterogeneous FCM DNA histograms, the presence of multiple stemlines was confirmed in IA DNA histograms in 16/19. In nine of these 16 cases, multiple DNA stemlines having similar DNA indices were present in both areas of neoplasm examined with IA. The remaining seven cases displayed unimodal IA histograms in both areas, however DNA indices differed between the two histograms. These findings imply that cell populations corresponding to flow cytometrically detected DNA stemlines are often intimately admixed, even within geographically separated portions of breast tumors. This pattern suggests that productive interactions between genetically distinct tumor populations may lead to stable co-dominance of ancestral clones during progression of some breast carcinomas. 12 refs., 4 tabs.

  2. Integrated genomic DNA/RNA profiling of hematologic malignancies in the clinical setting

    PubMed Central

    He, Jie; Abdel-Wahab, Omar; Nahas, Michelle K.; Wang, Kai; Rampal, Raajit K.; Intlekofer, Andrew M.; Patel, Jay; Krivstov, Andrei; Frampton, Garrett M.; Young, Lauren E.; Zhong, Shan; Bailey, Mark; White, Jared R.; Roels, Steven; Deffenbaugh, Jason; Fichtenholtz, Alex; Brennan, Timothy; Rosenzweig, Mark; Pelak, Kimberly; Knapp, Kristina M.; Brennan, Kristina W.; Donahue, Amy L.; Young, Geneva; Garcia, Lazaro; Beckstrom, Selmira T.; Zhao, Mandy; White, Emily; Banning, Vera; Buell, Jamie; Iwanik, Kiel; Ross, Jeffrey S.; Morosini, Deborah; Younes, Anas; Hanash, Alan M.; Paietta, Elisabeth; Roberts, Kathryn; Mullighan, Charles; Dogan, Ahmet; Armstrong, Scott A.; Mughal, Tariq; Vergilio, Jo-Anne; Labrecque, Elaine; Erlich, Rachel; Vietz, Christine; Yelensky, Roman; Stephens, Philip J.; Miller, Vincent A.; van den Brink, Marcel R. M.; Otto, Geoff A.; Lipson, Doron

    2016-01-01

    The spectrum of somatic alterations in hematologic malignancies includes substitutions, insertions/deletions (indels), copy number alterations (CNAs), and a wide range of gene fusions; no current clinically available single assay captures the different types of alterations. We developed a novel next-generation sequencing-based assay to identify all classes of genomic alterations using archived formalin-fixed paraffin-embedded blood and bone marrow samples with high accuracy in a clinically relevant time frame, which is performed in our Clinical Laboratory Improvement Amendments–certified College of American Pathologists–accredited laboratory. Targeted capture of DNA/RNA and next-generation sequencing reliably identifies substitutions, indels, CNAs, and gene fusions, with similar accuracy to lower-throughput assays that focus on specific genes and types of genomic alterations. Profiling of 3696 samples identified recurrent somatic alterations that impact diagnosis, prognosis, and therapy selection. This comprehensive genomic profiling approach has proved effective in detecting all types of genomic alterations, including fusion transcripts, which increases the ability to identify clinically relevant genomic alterations with therapeutic relevance. PMID:26966091

  3. Integrated genomic DNA/RNA profiling of hematologic malignancies in the clinical setting.

    PubMed

    He, Jie; Abdel-Wahab, Omar; Nahas, Michelle K; Wang, Kai; Rampal, Raajit K; Intlekofer, Andrew M; Patel, Jay; Krivstov, Andrei; Frampton, Garrett M; Young, Lauren E; Zhong, Shan; Bailey, Mark; White, Jared R; Roels, Steven; Deffenbaugh, Jason; Fichtenholtz, Alex; Brennan, Timothy; Rosenzweig, Mark; Pelak, Kimberly; Knapp, Kristina M; Brennan, Kristina W; Donahue, Amy L; Young, Geneva; Garcia, Lazaro; Beckstrom, Selmira T; Zhao, Mandy; White, Emily; Banning, Vera; Buell, Jamie; Iwanik, Kiel; Ross, Jeffrey S; Morosini, Deborah; Younes, Anas; Hanash, Alan M; Paietta, Elisabeth; Roberts, Kathryn; Mullighan, Charles; Dogan, Ahmet; Armstrong, Scott A; Mughal, Tariq; Vergilio, Jo-Anne; Labrecque, Elaine; Erlich, Rachel; Vietz, Christine; Yelensky, Roman; Stephens, Philip J; Miller, Vincent A; van den Brink, Marcel R M; Otto, Geoff A; Lipson, Doron; Levine, Ross L

    2016-06-16

    The spectrum of somatic alterations in hematologic malignancies includes substitutions, insertions/deletions (indels), copy number alterations (CNAs), and a wide range of gene fusions; no current clinically available single assay captures the different types of alterations. We developed a novel next-generation sequencing-based assay to identify all classes of genomic alterations using archived formalin-fixed paraffin-embedded blood and bone marrow samples with high accuracy in a clinically relevant time frame, which is performed in our Clinical Laboratory Improvement Amendments-certified College of American Pathologists-accredited laboratory. Targeted capture of DNA/RNA and next-generation sequencing reliably identifies substitutions, indels, CNAs, and gene fusions, with similar accuracy to lower-throughput assays that focus on specific genes and types of genomic alterations. Profiling of 3696 samples identified recurrent somatic alterations that impact diagnosis, prognosis, and therapy selection. This comprehensive genomic profiling approach has proved effective in detecting all types of genomic alterations, including fusion transcripts, which increases the ability to identify clinically relevant genomic alterations with therapeutic relevance. PMID:26966091

  4. DNA.

    ERIC Educational Resources Information Center

    Felsenfeld, Gary

    1985-01-01

    Structural form, bonding scheme, and chromatin structure of and gene-modification experiments with deoxyribonucleic acid (DNA) are described. Indicates that DNA's double helix is variable and also flexible as it interacts with regulatory and other molecules to transfer hereditary messages. (DH)

  5. A novel parallel architecture for local histogram equalization

    NASA Astrophysics Data System (ADS)

    Ohannessian, Mesrob I.; Choueiter, Ghinwa F.; Diab, Hassan

    2005-07-01

    Local histogram equalization is an image enhancement algorithm that has found wide application in the pre-processing stage of areas such as computer vision, pattern recognition and medical imaging. The computationally intensive nature of the procedure, however, is a main limitation when real time interactive applications are in question. This work explores the possibility of performing parallel local histogram equalization, using an array of special purpose elementary processors, through an HDL implementation that targets FPGA or ASIC platforms. A novel parallelization scheme is presented and the corresponding architecture is derived. The algorithm is reduced to pixel-level operations. Processing elements are assigned image blocks, to maintain a reasonable performance-cost ratio. To further simplify both processor and memory organizations, a bit-serial access scheme is used. A brief performance assessment is provided to illustrate and quantify the merit of the approach.

  6. Brain tumor CT attenuation coefficients: semiquantitative analysis of histograms.

    PubMed

    Ratzka, M; Haubitz, I

    1983-01-01

    This paper reports on work in progress on semiquantitative curve analyses of histograms of brain tumors. Separation of statistical groups of attenuation values obtained by computer calculation is done separately from scanning, using histogram printouts as the data input for a programmable calculator. This method is discussed together with its results in 50 cases of malignant gliomas. The detection of hidden tissue portions and the more accurate evaluation of partial enhancement effects have been the investigators' main concerns to the present time; however, this method may allow more specific diagnosis of malignancy and changes in tumor characteristics than visual assessment alone. This has not been proven by studies that have evaluated large numbers of cases, but seems to be worth pursuing as a new approach. PMID:6410783

  7. Fingerprint image segmentation based on multi-features histogram analysis

    NASA Astrophysics Data System (ADS)

    Wang, Peng; Zhang, Youguang

    2007-11-01

    An effective fingerprint image segmentation based on multi-features histogram analysis is presented. We extract a new feature, together with three other features to segment fingerprints. Two of these four features, each of which is related to one of the other two, are reciprocals with each other, so features are divided into two groups. These two features' histograms are calculated respectively to determine which feature group is introduced to segment the aim-fingerprint. The features could also divide fingerprints into two classes with high and low quality. Experimental results show that our algorithm could classify foreground and background effectively with lower computational cost, and it can also reduce pseudo-minutiae detected and improve the performance of AFIS.

  8. Improved dose-volume histogram estimates for radiopharmaceutical therapy by optimizing quantitative SPECT reconstruction parameters

    NASA Astrophysics Data System (ADS)

    Cheng, Lishui; Hobbs, Robert F.; Segars, Paul W.; Sgouros, George; Frey, Eric C.

    2013-06-01

    In radiopharmaceutical therapy, an understanding of the dose distribution in normal and target tissues is important for optimizing treatment. Three-dimensional (3D) dosimetry takes into account patient anatomy and the nonuniform uptake of radiopharmaceuticals in tissues. Dose-volume histograms (DVHs) provide a useful summary representation of the 3D dose distribution and have been widely used for external beam treatment planning. Reliable 3D dosimetry requires an accurate 3D radioactivity distribution as the input. However, activity distribution estimates from SPECT are corrupted by noise and partial volume effects (PVEs). In this work, we systematically investigated OS-EM based quantitative SPECT (QSPECT) image reconstruction in terms of its effect on DVHs estimates. A modified 3D NURBS-based Cardiac-Torso (NCAT) phantom that incorporated a non-uniform kidney model and clinically realistic organ activities and biokinetics was used. Projections were generated using a Monte Carlo (MC) simulation; noise effects were studied using 50 noise realizations with clinical count levels. Activity images were reconstructed using QSPECT with compensation for attenuation, scatter and collimator-detector response (CDR). Dose rate distributions were estimated by convolution of the activity image with a voxel S kernel. Cumulative DVHs were calculated from the phantom and QSPECT images and compared both qualitatively and quantitatively. We found that noise, PVEs, and ringing artifacts due to CDR compensation all degraded histogram estimates. Low-pass filtering and early termination of the iterative process were needed to reduce the effects of noise and ringing artifacts on DVHs, but resulted in increased degradations due to PVEs. Large objects with few features, such as the liver, had more accurate histogram estimates and required fewer iterations and more smoothing for optimal results. Smaller objects with fine details, such as the kidneys, required more iterations and less

  9. Improved dose-volume histogram estimates for radiopharmaceutical therapy by optimizing quantitative SPECT reconstruction parameters.

    PubMed

    Cheng, Lishui; Hobbs, Robert F; Segars, Paul W; Sgouros, George; Frey, Eric C

    2013-06-01

    In radiopharmaceutical therapy, an understanding of the dose distribution in normal and target tissues is important for optimizing treatment. Three-dimensional (3D) dosimetry takes into account patient anatomy and the nonuniform uptake of radiopharmaceuticals in tissues. Dose-volume histograms (DVHs) provide a useful summary representation of the 3D dose distribution and have been widely used for external beam treatment planning. Reliable 3D dosimetry requires an accurate 3D radioactivity distribution as the input. However, activity distribution estimates from SPECT are corrupted by noise and partial volume effects (PVEs). In this work, we systematically investigated OS-EM based quantitative SPECT (QSPECT) image reconstruction in terms of its effect on DVHs estimates. A modified 3D NURBS-based Cardiac-Torso (NCAT) phantom that incorporated a non-uniform kidney model and clinically realistic organ activities and biokinetics was used. Projections were generated using a Monte Carlo (MC) simulation; noise effects were studied using 50 noise realizations with clinical count levels. Activity images were reconstructed using QSPECT with compensation for attenuation, scatter and collimator-detector response (CDR). Dose rate distributions were estimated by convolution of the activity image with a voxel S kernel. Cumulative DVHs were calculated from the phantom and QSPECT images and compared both qualitatively and quantitatively. We found that noise, PVEs, and ringing artifacts due to CDR compensation all degraded histogram estimates. Low-pass filtering and early termination of the iterative process were needed to reduce the effects of noise and ringing artifacts on DVHs, but resulted in increased degradations due to PVEs. Large objects with few features, such as the liver, had more accurate histogram estimates and required fewer iterations and more smoothing for optimal results. Smaller objects with fine details, such as the kidneys, required more iterations and less

  10. Flood detection/monitoring using adjustable histogram equalization technique.

    PubMed

    Nazir, Fakhera; Riaz, Muhammad Mohsin; Ghafoor, Abdul; Arif, Fahim

    2014-01-01

    Flood monitoring technique using adjustable histogram equalization is proposed. The technique overcomes the limitations (overenhancement, artifacts, and unnatural look) of existing technique by adjusting the contrast of images. The proposed technique takes pre- and postimages and applies different processing steps for generating flood map without user interaction. The resultant flood maps can be used for flood monitoring and detection. Simulation results show that the proposed technique provides better output quality compared to the state of the art existing technique. PMID:24558332

  11. Flood Detection/Monitoring Using Adjustable Histogram Equalization Technique

    PubMed Central

    Riaz, Muhammad Mohsin; Ghafoor, Abdul

    2014-01-01

    Flood monitoring technique using adjustable histogram equalization is proposed. The technique overcomes the limitations (overenhancement, artifacts, and unnatural look) of existing technique by adjusting the contrast of images. The proposed technique takes pre- and postimages and applies different processing steps for generating flood map without user interaction. The resultant flood maps can be used for flood monitoring and detection. Simulation results show that the proposed technique provides better output quality compared to the state of the art existing technique. PMID:24558332

  12. Slope histogram distribution-based parametrisation of Martian geomorphic features

    NASA Astrophysics Data System (ADS)

    Balint, Zita; Székely, Balázs; Kovács, Gábor

    2014-05-01

    The application of geomorphometric methods on the large Martian digital topographic datasets paves the way to analyse the Martian areomorphic processes in more detail. One of the numerous methods is the analysis is to analyse local slope distributions. To this implementation a visualization program code was developed that allows to calculate the local slope histograms and to compare them based on Kolmogorov distance criterion. As input data we used the digital elevation models (DTMs) derived from HRSC high-resolution stereo camera image from various Martian regions. The Kolmogorov-criterion based discrimination produces classes of slope histograms that displayed using coloration obtaining an image map. In this image map the distribution can be visualized by their different colours representing the various classes. Our goal is to create a local slope histogram based classification for large Martian areas in order to obtain information about general morphological characteristics of the region. This is a contribution of the TMIS.ascrea project, financed by the Austrian Research Promotion Agency (FFG). The present research is partly realized in the frames of TÁMOP 4.2.4.A/2-11-1-2012-0001 high priority "National Excellence Program - Elaborating and Operating an Inland Student and Researcher Personal Support System convergence program" project's scholarship support, using Hungarian state and European Union funds and cofinances from the European Social Fund.

  13. Contrast Enhancement Algorithm Based on Gap Adjustment for Histogram Equalization.

    PubMed

    Chiu, Chung-Cheng; Ting, Chih-Chung

    2016-01-01

    Image enhancement methods have been widely used to improve the visual effects of images. Owing to its simplicity and effectiveness histogram equalization (HE) is one of the methods used for enhancing image contrast. However, HE may result in over-enhancement and feature loss problems that lead to unnatural look and loss of details in the processed images. Researchers have proposed various HE-based methods to solve the over-enhancement problem; however, they have largely ignored the feature loss problem. Therefore, a contrast enhancement algorithm based on gap adjustment for histogram equalization (CegaHE) is proposed. It refers to a visual contrast enhancement algorithm based on histogram equalization (VCEA), which generates visually pleasing enhanced images, and improves the enhancement effects of VCEA. CegaHE adjusts the gaps between two gray values based on the adjustment equation, which takes the properties of human visual perception into consideration, to solve the over-enhancement problem. Besides, it also alleviates the feature loss problem and further enhances the textures in the dark regions of the images to improve the quality of the processed images for human visual perception. Experimental results demonstrate that CegaHE is a reliable method for contrast enhancement and that it significantly outperforms VCEA and other methods. PMID:27338412

  14. Contrast Enhancement Algorithm Based on Gap Adjustment for Histogram Equalization

    PubMed Central

    Chiu, Chung-Cheng; Ting, Chih-Chung

    2016-01-01

    Image enhancement methods have been widely used to improve the visual effects of images. Owing to its simplicity and effectiveness histogram equalization (HE) is one of the methods used for enhancing image contrast. However, HE may result in over-enhancement and feature loss problems that lead to unnatural look and loss of details in the processed images. Researchers have proposed various HE-based methods to solve the over-enhancement problem; however, they have largely ignored the feature loss problem. Therefore, a contrast enhancement algorithm based on gap adjustment for histogram equalization (CegaHE) is proposed. It refers to a visual contrast enhancement algorithm based on histogram equalization (VCEA), which generates visually pleasing enhanced images, and improves the enhancement effects of VCEA. CegaHE adjusts the gaps between two gray values based on the adjustment equation, which takes the properties of human visual perception into consideration, to solve the over-enhancement problem. Besides, it also alleviates the feature loss problem and further enhances the textures in the dark regions of the images to improve the quality of the processed images for human visual perception. Experimental results demonstrate that CegaHE is a reliable method for contrast enhancement and that it significantly outperforms VCEA and other methods. PMID:27338412

  15. Finding significantly connected voxels based on histograms of connection strengths

    NASA Astrophysics Data System (ADS)

    Kasenburg, Niklas; Pedersen, Morten Vester; Darkner, Sune

    2016-03-01

    We explore a new approach for structural connectivity based segmentations of subcortical brain regions. Connectivity based segmentations are usually based on fibre connections from a seed region to predefined target regions. We present a method for finding significantly connected voxels based on the distribution of connection strengths. Paths from seed voxels to all voxels in a target region are obtained from a shortest-path tractography. For each seed voxel we approximate the distribution with a histogram of path scores. We hypothesise that the majority of estimated connections are false-positives and that their connection strength is distributed differently from true-positive connections. Therefore, an empirical null-distribution is defined for each target region as the average normalized histogram over all voxels in the seed region. Single histograms are then tested against the corresponding null-distribution and significance is determined using the false discovery rate (FDR). Segmentations are based on significantly connected voxels and their FDR. In this work we focus on the thalamus and the target regions were chosen by dividing the cortex into a prefrontal/temporal zone, motor zone, somatosensory zone and a parieto-occipital zone. The obtained segmentations consistently show a sparse number of significantly connected voxels that are located near the surface of the anterior thalamus over a population of 38 subjects.

  16. Clinical Potential of DNA Methylation in Gastric Cancer: A Meta-Analysis

    PubMed Central

    Sapari, Nur Sabrina; Loh, Marie; Vaithilingam, Aparna; Soong, Richie

    2012-01-01

    Background Accumulating evidence indicates aberrant DNA methylation is involved in gastric tumourigenesis, suggesting it may be a useful clinical biomarker for the disease. The aim of this study was to consolidate and summarize published data on the potential of methylation in gastric cancer (GC) risk prediction, prognostication and prediction of treatment response. Methods Relevant studies were identified from PubMed using a systematic search approach. Results were summarized by meta-analysis. Mantel-Haenszel odds ratios were computed for each methylation event assuming the random-effects model. Results A review of 589 retrieved publications identified 415 relevant articles, including 143 case-control studies on gene methylation of 142 individual genes in GC clinical samples. A total of 77 genes were significantly differentially methylated between tumour and normal gastric tissue from GC subjects, of which data on 62 was derived from single studies. Methylation of 15, 4 and 7 genes in normal gastric tissue, plasma and serum respectively was significantly different in frequency between GC and non-cancer subjects. A prognostic significance was reported for 18 genes and predictive significance was reported for p16 methylation, although many inconsistent findings were also observed. No bias due to assay, use of fixed tissue or CpG sites analysed was detected, however a slight bias towards publication of positive findings was observed. Conclusions DNA methylation is a promising biomarker for GC risk prediction and prognostication. Further focused validation of candidate methylation markers in independent cohorts is required to develop its clinical potential. PMID:22558417

  17. Implementing a 3D histogram version of the Energy-Test in ROOT

    NASA Astrophysics Data System (ADS)

    Cohen, E. O.; Reid, I. D.; Piasetzky, E.

    2016-08-01

    Comparing simulation and data histograms is of interest in nuclear and particle physics experiments; however, the leading three-dimensional histogram comparison tool available in ROOT, the 3D Kolmogorov-Smirnov test, exhibits shortcomings. Throughout the following, we present and discuss the implementation of an alternative comparison test for three-dimensional histograms, based on the Energy-Test by Aslan and Zech.

  18. Evolving approach and clinical significance of detecting DNA mismatch repair deficiency in colorectal carcinoma

    PubMed Central

    Shia, Jinru

    2016-01-01

    The last two decades have seen significant advancement in our understanding of colorectal tumors with DNA mismatch repair (MMR) deficiency. The ever-emerging revelations of new molecular and genetic alterations in various clinical conditions have necessitated constant refinement of disease terminology and classification. Thus, a case with the clinical condition of hereditary non-polyposis colorectal cancer as defined by the Amsterdam criteria may be one of Lynch syndrome characterized by a germline defect in one of the several MMR genes, one of the yet-to-be-defined “Lynch-like syndrome” if there is evidence of MMR deficiency in the tumor but no detectable germline MMR defect or tumor MLH1 promoter methylation, or “familial colorectal cancer type X” if there is no evidence of MMR deficiency. The detection of these conditions carries significant clinical implications. The detection tools and strategies are constantly evolving. The Bethesda guidelines symbolize a selective approach that uses clinical information and tumor histology as the basis to select high-risk individuals. Such a selective approach has subsequently been found to have limited sensitivity, and is thus gradually giving way to the alternative universal approach that tests all newly diagnosed colorectal cancers. Notably, the universal approach also has its own limitations; its cost-effectiveness in real practice, in particular, remains to be determined. Meanwhile, technological advances such as the next-generation sequencing are offering the promise of direct genetic testing for MMR deficiency at an affordable cost probably in the near future. This article reviews the up-to-date molecular definitions of the various conditions related to MMR deficiency, and discusses the tools and strategies that have been used in detecting these conditions. Special emphasis will be placed on the evolving nature and the clinical importance of the disease definitions and the detection strategies. PMID:25716099

  19. Clinical trial design issues raised during recombinant DNA advisory committee review of gene transfer protocols.

    PubMed

    Scharschmidt, Tiffany; Lo, Bernard

    2006-04-01

    Gene transfer clinical trial protocols are reviewed by the Recombinant DNA Advisory Committee (RAC). Identifying the design concerns and suggestions commonly raised during RAC review may help investigators and sponsors shorten the process of protocol development and improve the quality of gene transfer trials. We therefore examined 53 full public reviews of gene transfer clinical trial protocols performed by the RAC between December 2000 and June 2004 to determine what trial design concerns or suggestions RAC members raised during written review or public discussion or in the formal letter to investigators after the review was completed. We also determined how frequently these concerns were raised. We found that RAC members raised issues regarding selection of subjects in 89% of reviews, dose escalation in 77%, selection of safety end points in 76%, biological activity measures in 66%, and overall design in 60% of reviews. The most common issue raised by RAC reviewers was the need to exclude subjects at increased risk for adverse events. Furthermore, in 89% of reviews, at least one design issue pertaining to safety of participants was raised. In 91% of reviews, at least one design concern was presented as a written RAC recommendation or concern to the investigator after the public review. When submitting protocols for RAC review, investigators and sponsors might devote more attention to issues that RAC reviewers commonly raise. Such attention might help strengthen clinical trial protocols, shorten the protocol development process, and enhance the protection of research participants. PMID:16610932

  20. Correlation between DNA ploidy, metaphase high-resolution comparative genomic hybridization results and clinical outcome of synovial sarcoma

    PubMed Central

    2011-01-01

    Background Although synovial sarcoma is the 3rd most commonly occurring mesenchymal tumor in young adults, usually with a highly aggressive clinical course; remarkable differences can be seen regarding the clinical outcome. According to comparative genomic hybridization (CGH) data published in the literature, the simple and complex karyotypes show a correlation between the prognosis and clinical outcome. In addition, the connection between DNA ploidy and clinical course is controversial. The aim of this study was using a fine-tuning interpretation of our DNA ploidy results and to compare these with metaphase high-resolution CGH (HR-CGH) results. Methods DNA ploidy was determined on Feulgen-stained smears in 56 synovial sarcoma cases by image cytometry; follow up was available in 46 cases (average: 78 months). In 9 cases HR-CGH analysis was also available. Results 10 cases were found DNA-aneuploid, 46 were DNA-diploid by image cytometry. With fine-tuning of the diploid cases according to the 5c exceeding events (single cell aneuploidy), 33 cases were so called "simple-diploid" (without 5c exceeding events) and 13 cases were "complex-diploid"; containing 5c exceeding events (any number). Aneuploid tumors contained large numbers of genetic alterations with the sum gain of at least 2 chromosomes (A-, B- or C-group) detected by HR-CGH. In the "simple-diploid" cases no or few genetic alterations could be detected, whereas the "complex-diploid" samples numerous aberrations (equal or more than 3) could be found. Conclusions Our results show a correlation between the DNA-ploidy, a fine-tuned DNA-ploidy and the HR-CGH results. Furthermore, we found significant correlation between the different ploidy groups and the clinical outcome (p < 0.05). PMID:22053830

  1. Quantitative characterization of metastatic disease in the spine. Part II. Histogram-based analyses

    SciTech Connect

    Whyne, Cari; Hardisty, Michael; Wu, Florence; Skrinskas, Tomas; Clemons, Mark; Gordon, Lyle; Basran, Parminder S.

    2007-08-15

    Radiological imaging is essential to the appropriate management of patients with bone metastasis; however, there have been no widely accepted guidelines as to the optimal method for quantifying the potential impact of skeletal lesions or to evaluate response to treatment. The current inability to rapidly quantify the response of bone metastases excludes patients with cancer and bone disease from participating in clinical trials of many new treatments as these studies frequently require patients with so-called measurable disease. Computed tomography (CT) can provide excellent skeletal detail with a sensitivity for the diagnosis of bone metastases. The purpose of this study was to establish an objective method to quantitatively characterize disease in the bony spine using CT-based segmentations. It was hypothesized that histogram analysis of CT vertebral density distributions would enable standardized segmentation of tumor tissue and consequently allow quantification of disease in the metastatic spine. Thirty two healthy vertebral CT scans were first studied to establish a baseline characterization. The histograms of the trabecular centrums were found to be Gaussian distributions (average root-mean-square difference=30 voxel counts), as expected for a uniform material. Intrapatient vertebral level similarity was also observed as the means were not significantly different (p>0.8). Thus, a patient-specific healthy vertebral body histogram is able to characterize healthy trabecular bone throughout that individual's thoracolumbar spine. Eleven metastatically involved vertebrae were analyzed to determine the characteristics of the lytic and blastic bone voxels relative to the healthy bone. Lytic and blastic tumors were segmented as connected areas with voxel intensities between specified thresholds. The tested thresholds were {mu}-1.0{sigma}, {mu}-1.5{sigma}, and {mu}-2.0{sigma}, for lytic and {mu}+2.0{sigma}, {mu}+3.0{sigma}, and {mu}+3.5{sigma} for blastic tissue where

  2. Prediction of brain tumor progression using multiple histogram matched MRI scans

    NASA Astrophysics Data System (ADS)

    Banerjee, Debrup; Tran, Loc; Li, Jiang; Shen, Yuzhong; McKenzie, Frederic; Wang, Jihong

    2011-03-01

    In a recent study [1], we investigated the feasibility of predicting brain tumor progression based on multiple MRI series and we tested our methods on seven patients' MRI images scanned at three consecutive visits A, B and C. Experimental results showed that it is feasible to predict tumor progression from visit A to visit C using a model trained by the information from visit A to visit B. However, the trained model failed when we tried to predict tumor progression from visit B to visit C, though it is clinically more important. Upon a closer look at the MRI scans revealed that histograms of MRI scans such as T1, T2, FLAIR etc taken at different times have slight shifts or different shapes. This is because those MRI scans are qualitative instead of quantitative so MRI scans taken at different times or by different scanners might have slightly different scales or have different homogeneities in the scanning region. In this paper, we proposed a method to overcome this difficulty. The overall goal of this study is to assess brain tumor progression by exploring seven patients' complete MRI records scanned during their visits in the past two years. There are ten MRI series in each visit, including FLAIR, T1-weighted, post-contrast T1-weighted, T2-weighted and five DTI derived MRI volumes: ADC, FA, Max, Min and Middle Eigen Values. After registering all series to the corresponding DTI scan at the first visit, we applied a histogram matching algorithm to non-DTI MRI scans to match their histograms to those of the corresponding MRI scans at the first visit. DTI derived series are quantitative and do not require the histogram matching procedure. A machine learning algorithm was then trained using the data containing information from visit A to visit B, and the trained model was used to predict tumor progression from visit B to visit C. An average of 72% pixel-wise accuracy was achieved for tumor progression prediction from visit B to visit C.

  3. [Distribution of nontuberculous mycobacteria isolated from clinical specimens and identified with DNA sequence analysis].

    PubMed

    Özçolpan, O Olcay; Sürücüoğlu, Süheyla; Özkütük, Nuri; Çavuşoğlu, Cengiz

    2015-10-01

    The aims of the study were to perform the identification of nontuberculous mycobacteria (NTM) isolated from different clinical specimens in the Mycobacteriology Laboratory of Celal Bayar University, Manisa (located at Aegean region of Turkey), by DNA sequence analysis, and to discuss the epidemiological aspects of the data obtained. Out of 5122 clinical specimens sent to the laboratory with the initial diagnosis of tuberculosis in the period April 2007 to July 2011, M.tuberculosis complex and NTM were identified in 225 (4.39%) and 126 (2.46%) samples, respectively. DNA sequence analysis by targeting hsp65 and 16S rDNA gene regions was performed on 101 of the NTM strains in Mycobacteriology Laboratory of Ege University, Izmir. DNA sequence analysis data was evaluated using RIDOM and GenBLAST data bases. NTM strains were identified as 40 M.porcinum (39.60%), 36 M.lentiflavum (35.65%), six M.abscessus (5.64%), five M.peregrinum (4.95%), four M.gordonae (3.96%), three M.fortuitum (2.97%), two M.chelonae (1.98%), and one for each M.alvei (0.99%), M.scrofulaceum (0.99%), M.kansasii (0.99%) species. Two strains which were both 95-98% compatible with other mycobacteria in the data bases could not be identified with certainty. Seventy-two (94.73%) strains of M.lentiflavum and M.porcinum, which were the most frequent (75.24%) species in the study, were isolated from bronchoalveolar lavage (BAL) specimens. The remaining 99 strains examined could not be proven as the cause of the disease due to absence of patients' clinical data, whereas two M.abscessus strains isolated from the sputum were considered as the cause of the disease according to the ATS/IDSA criteria. The isolation rate of NTM in 2010 was found significantly higher (5.33%) than previous years. Review of the 2010 data showed that all strains of M.porcinum and M.lentiflavum, which were the most frequently identified strains were isolated from BAL specimens. This situation is in line with the start of using of an

  4. [Clinical features and DGUOK mutations of an infant with mitochondrial DNA depletion syndrome].

    PubMed

    Deng, Mei; Lin, Wei-Xia; Guo, Li; Zhang, Zhan-Hui; Song, Yuan-Zong

    2016-06-01

    The aim of this study was to investigate the clinical features and DGUOK gene mutations of an infant with mitochondrial DNA depletion syndrome (MDS). The patient (more than 7 months old) manifested as hepatosplenomegaly, abnormal liver function, nystagmus and psychomotor retardation. Genetic DNA was extracted from peripheral blood samples of the patient and her parents. Targeted Exome Sequencing was performed to explore the genetic causes. Sanger sequencing was carried out to confirm the detected mutations. The sequencing results showed that the patient was a compound heterozygote for c.679G>A and c.817delT in the DGUOK gene. The former was a reportedly pathogenic missense mutation of maternal origin, while the latter, a frameshift mutation from the father, has not been described yet. The findings in this study expand the mutation spectrum of DGUOK gene, and provide molecular evidence for the etiologic diagnosis of the patient as well as for the genetic counseling and prenatal diagnosis in the family. PMID:27324545

  5. Expression of O6-methylguanine DNA methyltransferase (MGMT) and its clinical significance in gastroenteropancreatic neuroendocrine neoplasm

    PubMed Central

    Yang, Qiu-Chen; Wang, Yu-Hong; Lin, Yuan; Xue, Ling; Chen, Yuan-Jia; Chen, Min-Hu; Chen, Jie

    2014-01-01

    O6-methylguanine-DNA methyltransferase (MGMT) is a widespread DNA repair enzyme defending against mutation caused by guanine O6-alkylating agents. Until now, we know only little about the expression of MGMT in gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN). To study the expression of MGMT and its clinical significance in GEP-NEN, 174 specimens of GEP-NEN were examined, of which 152 specimens came from The First Affiliated Hospital, Sun Yat-sen University during October 1995 to November 2013, 22 specimens came from Peking Union Medical College Hospital during September 2004 to April 2010. MGMT protein was detected with EnVision immunohistochemical staining method. Clinicopathological factors were also collected and analyzed. We observed that the overall expression rate of MGMT was 83.9%. Over expression of MGMT protein was not associated with sex, age, functional status, primary tumor location, grading, classification, TNM stage and metastasis (P > 0.05). Kaplan-Meier analysis revealed that there was no significant difference in survival between MGMT-positive and MGMT-negative tumors of GEP-NEN patients (χ2 = 0.887, P = 0.346). In multivariate analyses carried out by Cox proportional hazards regression model, MGMT expression was also not an independent predictors of survival. These results demonstrated that MGMT protein was highly expressed in GEP-NEN. MGMT deficiency rate was similar in pancreatic NEN and in gastrointestinal NEN. MGMT expression was not correlated with prognosis of GEP-NEN. PMID:25120800

  6. Content based Image Retrieval based on Different Global and Local Color Histogram Methods: A Survey

    NASA Astrophysics Data System (ADS)

    Suhasini, Pallikonda Sarah; Sri Rama Krishna, K.; Murali Krishna, I. V.

    2016-06-01

    Different global and local color histogram methods for content based image retrieval (CBIR) are investigated in this paper. Color histogram is a widely used descriptor for CBIR. Conventional method of extracting color histogram is global, which misses the spatial content, is less invariant to deformation and viewpoint changes, and results in a very large three dimensional histogram corresponding to the color space used. To address the above deficiencies, different global and local histogram methods are proposed in recent research. Different ways of extracting local histograms to have spatial correspondence, invariant colour histogram to add deformation and viewpoint invariance and fuzzy linking method to reduce the size of the histogram are found in recent papers. The color space and the distance metric used are vital in obtaining color histogram. In this paper the performance of CBIR based on different global and local color histograms in three different color spaces, namely, RGB, HSV, L*a*b* and also with three distance measures Euclidean, Quadratic and Histogram intersection are surveyed, to choose appropriate method for future research.

  7. Ribosomal DNA Sequencing for Identification of Aerobic Gram-Positive Rods in the Clinical Laboratory (an 18-Month Evaluation)

    PubMed Central

    Bosshard, P. P.; Abels, S.; Zbinden, R.; Böttger, E. C.; Altwegg, M.

    2003-01-01

    We have evaluated over a period of 18 months the use of 16S ribosomal DNA (rDNA) sequence analysis as a means of identifying aerobic gram-positive rods in the clinical laboratory. Two collections of strains were studied: (i) 37 clinical strains of gram-positive rods well identified by phenotypic tests, and (ii) 136 clinical isolates difficult to identify by standard microbiological investigations, i.e., identification at the species level was impossible. Results of molecular analyses were compared with those of conventional phenotypic identification procedures. Good overall agreement between phenotypic and molecular identification procedures was found for the collection of 37 clinical strains well identified by conventional means. For the 136 clinical strains which were difficult to identify by standard microbiological investigations, phenotypic characterization identified 71 of 136 (52.2%) isolates at the genus level; 65 of 136 (47.8%) isolates could not be discriminated at any taxonomic level. In comparison, 16S rDNA sequencing identified 89 of 136 (65.4%) isolates at the species level, 43 of 136 (31.6%) isolates at the genus level, and 4 of 136 (2.9%) isolates at the family level. We conclude that (i) rDNA sequencing is an effective means for the identification of aerobic gram-positive rods which are difficult to identify by conventional techniques, and (ii) molecular identification procedures are not required for isolates well identified by phenotypic investigations. PMID:12958237

  8. Epstein-Barr virus DNA load in chronic lymphocytic leukemia is an independent predictor of clinical course and survival

    PubMed Central

    Visco, Carlo; Falisi, Erika; Young, Ken H.; Pascarella, Michela; Perbellini, Omar; Carli, Giuseppe; Novella, Elisabetta; Rossi, Davide; Giaretta, Ilaria; Cavallini, Chiara; Scupoli, Maria Teresa; De Rossi, Anita; D'Amore, Emanuele Stefano Giovanni; Rassu, Mario; Gaidano, Gianluca; Pizzolo, Giovanni; Ambrosetti, Achille; Rodeghiero, Francesco

    2015-01-01

    The relation between Epstein-Barr virus (EBV) DNA load and clinical course of patients with chronic lymphocytic leukemia (CLL) is unknown. We assessed EBV DNA load by quantitative PCR at CLL presentation in mononuclear cells (MNC) of 220 prospective patients that were enrolled and followed-up in two major Institutions. In 20 patients EBV DNA load was also assessed on plasma samples. Forty-one age-matched healthy subjects were tested for EBV DNA load on MNC. Findings were validated in an independent retrospective cohort of 112 patients with CLL. EBV DNA load was detectable in 59%, and high (≥2000 copies/µg DNA) in 19% of patients, but it was negative in plasma samples. EBV DNA load was significantly higher in CLL patients than in healthy subjects (P < .0001). No relation was found between high EBV load and clinical stage or biological variables, except for 11q deletion (P = .004), CD38 expression (P = .003), and NOTCH1 mutations (P = .05). High EBV load led to a 3.14-fold increase in the hazard ratio of death and to a shorter overall survival (OS; P = .001). Poor OS was attributable, at least in part, to shorter time-to-first-treatment (P = .0008), with no higher risk of Richter's transformation or second cancer. Multivariate analysis selected high levels of EBV load as independent predictor of OS after controlling for confounding clinical and biological variables. EBV DNA load at presentation is an independent predictor of OS in patients with CLL. PMID:26087198

  9. Epstein-Barr virus DNA load in chronic lymphocytic leukemia is an independent predictor of clinical course and survival.

    PubMed

    Visco, Carlo; Falisi, Erika; Young, Ken H; Pascarella, Michela; Perbellini, Omar; Carli, Giuseppe; Novella, Elisabetta; Rossi, Davide; Giaretta, Ilaria; Cavallini, Chiara; Scupoli, Maria Teresa; De Rossi, Anita; D'Amore, Emanuele Stefano Giovanni; Rassu, Mario; Gaidano, Gianluca; Pizzolo, Giovanni; Ambrosetti, Achille; Rodeghiero, Francesco

    2015-07-30

    The relation between Epstein-Barr virus (EBV) DNA load and clinical course of patients with chronic lymphocytic leukemia (CLL) is unknown. We assessed EBV DNA load by quantitative PCR at CLL presentation in mononuclear cells (MNC) of 220 prospective patients that were enrolled and followed-up in two major Institutions. In 20 patients EBV DNA load was also assessed on plasma samples. Forty-one age-matched healthy subjects were tested for EBV DNA load on MNC. Findings were validated in an independent retrospective cohort of 112 patients with CLL. EBV DNA load was detectable in 59%, and high (≥2000 copies/µg DNA) in 19% of patients, but it was negative in plasma samples. EBV DNA load was significantly higher in CLL patients than in healthy subjects (P < .0001). No relation was found between high EBV load and clinical stage or biological variables, except for 11q deletion (P = .004), CD38 expression (P = .003), and NOTCH1 mutations (P = .05). High EBV load led to a 3.14-fold increase in the hazard ratio of death and to a shorter overall survival (OS; P = .001). Poor OS was attributable, at least in part, to shorter time-to-first-treatment (P = .0008), with no higher risk of Richter's transformation or second cancer. Multivariate analysis selected high levels of EBV load as independent predictor of OS after controlling for confounding clinical and biological variables. EBV DNA load at presentation is an independent predictor of OS in patients with CLL. PMID:26087198

  10. Robust human intrusion detection technique using hue-saturation histograms

    NASA Astrophysics Data System (ADS)

    Hassan, Waqas; Mitra, Bhargav; Bangalore, Nagachetan; Birch, Philip; Young, Rupert; Chatwin, Chris

    2011-04-01

    A robust human intrusion detection technique using hue-saturation histograms is presented in this paper. Initially a region of interest (ROI) is manually identified in the scene viewed by a single fixed CCTV camera. All objects in the ROI are automatically demarcated from the background using brightness and chromaticity distortion parameters. The segmented objects are then tracked using correlation between hue-saturation based bivariate distributions. The technique has been applied on all the 'Sterile Zone' sequences of the United Kingdom Home Office iLIDS dataset and its performance is evaluated with over 70% positive results.

  11. Image segmentation using random-walks on the histogram

    NASA Astrophysics Data System (ADS)

    Morin, Jean-Philippe; Desrosiers, Christian; Duong, Luc

    2012-02-01

    This document presents a novel method for the problem of image segmentation, based on random-walks. This method shares similarities with the Mean-shift algorithm, as it finds the modes of the intensity histogram of images. However, unlike Mean-shift, our proposed method is stochastic and also provides class membership probabilities. Also, unlike other random-walk based methods, our approach does not require any form of user interaction, and can scale to very large images. To illustrate the usefulness, efficiency and scalability of our method, we test it on the task of segmenting anatomical structures present in cardiac CT and brain MRI images.

  12. Classification of CT-brain slices based on local histograms

    NASA Astrophysics Data System (ADS)

    Avrunin, Oleg G.; Tymkovych, Maksym Y.; Pavlov, Sergii V.; Timchik, Sergii V.; Kisała, Piotr; Orakbaev, Yerbol

    2015-12-01

    Neurosurgical intervention is a very complicated process. Modern operating procedures based on data such as CT, MRI, etc. Automated analysis of these data is an important task for researchers. Some modern methods of brain-slice segmentation use additional data to process these images. Classification can be used to obtain this information. To classify the CT images of the brain, we suggest using local histogram and features extracted from them. The paper shows the process of feature extraction and classification CT-slices of the brain. The process of feature extraction is specialized for axial cross-section of the brain. The work can be applied to medical neurosurgical systems.

  13. mRNA and DNA Detection of Human Papillomaviruses in Women of All Ages Attending Two Colposcopy Clinics

    PubMed Central

    Spathis, Aris; Kottaridi, Christine; Chranioti, Aikaterini; Meristoudis, Christos; Chrelias, Charalambos; Panayiotides, Ioannis G.; Paraskevaidis, Evangelos; Karakitsos, Petros

    2012-01-01

    Objective HPV infection is a common finding, especially in young women while the majority of infections are cleared within a short time interval. The aim of this study was to examine the efficacy of HPV DNA and mRNA testing in a population attending colposcopy units of two University hospitals. Methods 1173 liquid based cervical samples from two colposcopy clinics were tested for HPV DNA positivity using a commercial typing kit and HPV E6/E7 mRNA positivity with a flow cytometry based commercial kit. Statistic measures were calculated for both molecular tests and morphological cytology and colposcopy diagnosis according to histology results. Results HPV DNA, high-risk HPV DNA, HPV16 or 18 DNA and HPV mRNA was detected in 55.5%, 50.6%, 20.1% and 29.7% of the cervical smears respectively. Concordance between the DNA and the mRNA test was 71.6% with their differences being statistically significant. Both tests’ positivity increased significantly as lesion grade progressed and both displayed higher positivity rates in samples from women under 30 years old. mRNA testing displayed similar NPV, slightly lower sensitivity but significantly higher specificity and PPV than DNA testing, except only when DNA positivity for either HPV16 or 18 was used. Conclusions Overall mRNA testing displayed higher clinical efficacy than DNA testing, either when used as a reflex test or as an ancillary test combined with morphology. Due to enhanced specificity of mRNA testing and its comparable sensitivity in ages under 25 or 30 years old, induction of mRNA testing in young women could be feasible if a randomized trial verifies these results. PMID:23166611

  14. Clinical Factors Associated with Sperm DNA Fragmentation in Male Patients with Infertility

    PubMed Central

    Komiya, Akira; Kato, Tomonori; Kawauchi, Yoko; Watanabe, Akihiko; Fuse, Hideki

    2014-01-01

    Objective. The clinical factors associated with sperm DNA fragmentation (SDF) were investigated in male patients with infertility. Materials and Methods. Fifty-four ejaculates from infertile Japanese males were used. Thirty-three and twenty-one were from the patients with varicoceles and idiopathic causes of infertility, respectively. We performed blood tests, including the serum sex hormone levels, and conventional and computer-assisted semen analyses. The sperm nuclear vacuolization (SNV) was evaluated using a high-magnification microscope. The SDF was evaluated using the sperm chromatin dispersion test (SCDt) to determine the SDF index (SDFI). The SDFI was compared with semen parameters and other clinical variables, including lifestyle factors. Results. The SDFI was 41.3 ± 22.2% (mean ± standard deviation) and did not depend on the cause of infertility. Chronic alcohol use increased the SDFI to 49.6 ± 23.3% compared with 33.9 ± 18.0% in nondrinkers. The SDFI was related to adverse conventional semen parameters and sperm motion characteristics and correlated with the serum FSH level. The SNV showed a tendency to increase with the SDFI. The multivariate analysis revealed that the sperm progressive motility and chronic alcohol use were significant predictors of the SDF. Conclusion. The SCDt should be offered to chronic alcohol users and those with decreased sperm progressive motility. PMID:25165747

  15. DNA

    ERIC Educational Resources Information Center

    Stent, Gunther S.

    1970-01-01

    This history for molecular genetics and its explanation of DNA begins with an analysis of the Golden Jubilee essay papers, 1955. The paper ends stating that the higher nervous system is the one major frontier of biological inquiry which still offers some romance of research. (Author/VW)

  16. Lean histogram of oriented gradients features for effective eye detection

    NASA Astrophysics Data System (ADS)

    Sharma, Riti; Savakis, Andreas

    2015-11-01

    Reliable object detection is very important in computer vision and robotics applications. The histogram of oriented gradients (HOG) is established as one of the most popular hand-crafted features, which along with support vector machine (SVM) classification provides excellent performance for object recognition. We investigate dimensionality deduction on HOG features in combination with SVM classifiers to obtain efficient feature representation and improved classification performance. In addition to lean HOG features, we explore descriptors resulting from dimensionality reduction on histograms of binary descriptors. We consider three-dimensionality reduction techniques: standard principal component analysis, random projections, a computationally efficient linear mapping that is data independent, and locality preserving projections (LPP), which learns the manifold structure of the data. Our methods focus on the application of eye detection and were tested on an eye database created using the BioID and FERET face databases. Our results indicate that manifold learning is beneficial to classification utilizing HOG features. To demonstrate the broader usefulness of lean HOG features for object class recognition, we evaluated our system's classification performance on the CalTech-101 dataset with favorable outcomes.

  17. In vivo resolution of oligomers with fluorescence photobleaching recovery histograms

    PubMed Central

    Youn, B.S.; Lepock, J.R.; Borrelli, M.J.; Jervis, E.J.

    2006-01-01

    Simple independent enzyme-catalyzed reactions distributed homogeneously throughout an aqueous environment cannot adequately explain the regulation of metabolic and other cellular processes in vivo. Such an unstructured system results in unacceptably slow substrate turnover rates and consumes inordinate amounts of cellular energy. Current approaches to resolving compartmentalization in living cells requires the partitioning of the molecular species in question such that its localization can be resolved with fluorescence microscopy. Standard imaging approaches will not resolve localization of protein activity for proteins that are ubiquitously distributed, but whose function requires a change in state of the protein. The small heat shock protein sHSP27 exists as both dimers and large multimers and is distributed homogeneously throughout the cytoplasm. A fusion of the green fluorescent protein variant S65T and sHSP27 is used to assess the ability of diffusion rate histograms to resolve compartmentalization of the 2 dominant oligomeric species of sHSP27. Diffusion rates were measured by multiphoton fluorescence photobleaching recovery. Under physiologic conditions, diffusion rate histograms resolved at least 2 diffusive transport rates within a living cell potentially corresponding to the large and small oligomers of sHSP27. Given that oligomerization is often a means of regulation, compartmentalization of different oligomer species could provide a means for efficient regulation and localization of sHsp27 activity. PMID:16817323

  18. Accelerated weight histogram method for exploring free energy landscapes

    SciTech Connect

    Lindahl, V.; Lidmar, J.; Hess, B.

    2014-07-28

    Calculating free energies is an important and notoriously difficult task for molecular simulations. The rapid increase in computational power has made it possible to probe increasingly complex systems, yet extracting accurate free energies from these simulations remains a major challenge. Fully exploring the free energy landscape of, say, a biological macromolecule typically requires sampling large conformational changes and slow transitions. Often, the only feasible way to study such a system is to simulate it using an enhanced sampling method. The accelerated weight histogram (AWH) method is a new, efficient extended ensemble sampling technique which adaptively biases the simulation to promote exploration of the free energy landscape. The AWH method uses a probability weight histogram which allows for efficient free energy updates and results in an easy discretization procedure. A major advantage of the method is its general formulation, making it a powerful platform for developing further extensions and analyzing its relation to already existing methods. Here, we demonstrate its efficiency and general applicability by calculating the potential of mean force along a reaction coordinate for both a single dimension and multiple dimensions. We make use of a non-uniform, free energy dependent target distribution in reaction coordinate space so that computational efforts are not wasted on physically irrelevant regions. We present numerical results for molecular dynamics simulations of lithium acetate in solution and chignolin, a 10-residue long peptide that folds into a β-hairpin. We further present practical guidelines for setting up and running an AWH simulation.

  19. Microcanonical thermostatistics analysis without histograms: Cumulative distribution and Bayesian approaches

    NASA Astrophysics Data System (ADS)

    Alves, Nelson A.; Morero, Lucas D.; Rizzi, Leandro G.

    2015-06-01

    Microcanonical thermostatistics analysis has become an important tool to reveal essential aspects of phase transitions in complex systems. An efficient way to estimate the microcanonical inverse temperature β(E) and the microcanonical entropy S(E) is achieved with the statistical temperature weighted histogram analysis method (ST-WHAM). The strength of this method lies on its flexibility, as it can be used to analyse data produced by algorithms with generalised sampling weights. However, for any sampling weight, ST-WHAM requires the calculation of derivatives of energy histograms H(E) , which leads to non-trivial and tedious binning tasks for models with continuous energy spectrum such as those for biomolecular and colloidal systems. Here, we discuss two alternative methods that avoid the need for such energy binning to obtain continuous estimates for H(E) in order to evaluate β(E) by using ST-WHAM: (i) a series expansion to estimate probability densities from the empirical cumulative distribution function (CDF), and (ii) a Bayesian approach to model this CDF. Comparison with a simple linear regression method is also carried out. The performance of these approaches is evaluated considering coarse-grained protein models for folding and peptide aggregation.

  20. The Transition Matrix in Flat-histogram Sampling

    NASA Astrophysics Data System (ADS)

    Brown, Gregory; Eisenbach, M.; Li, Y. W.; Stocks, G. M.; Nicholson, D. M.; Odbadrakh, Kh.; Rikvold, P. A.

    2015-03-01

    Calculating the thermodynamic density of states (DOS) via flat-histogram sampling is a powerful numerical method for characterizing the temperature-dependent properties of materials. Since the calculated DOS is refined directly from the statistics of the sampling, methods of accelerating the sampling, e.g. through windowing and slow forcing, skew the resulting DOS. Calculating the infinite-temperature transition matrix during the flat-histogram sampling decouples the sampling from estimating the DOS, and allows the techniques of Transition Matrix Monte Carlo to be applied. This enables the calculation of the properties for very large system sizes and thus finite-size scaling analysis of the specific heat, magnetic susceptibility, and cumulant crossings at critical points. We discuss these developments in the context of models for magnetocaloric and spin-crossover materials. This work was performed at the Oak Ridge National Laboratory, which is managed by UT-Battelle for the U.S. Department of Energy. It was sponsored by the U.S. Department of Energy, Office of Basic Energy Sciences, Office of Advanced Scientific Computing Research, and the Oak Ridge Leadership Computing Facility. PAR is supported by the National Science Foundation.

  1. A preliminary evaluation of histogram-based binarization algorithms

    SciTech Connect

    Kanai, Junichi; Grover, K.

    1995-04-01

    To date, most Optical Character Recognition (OCR) systems process binary document images, and the quality of the input image strongly affects their performance. Since a binarization process is inherently lossy, different algorithms typically produce different binary images from the same gray scale image. The objective of this research is to study effects of global binarization algorithms on the performance of OCR systems. Several binarization methods were examined: the best fixed threshold value for the data set, the ideal histogram method, and Otsu`s algorithm. Four contemporary OCR systems and 50 hard copy pages containing 91,649 characters were used in the experiments. These pages were digitized at 300 dpi and 8 bits/pixel, and 36 different threshold values (ranging from 59 to 199 in increments of) 4 were used. The resulting 1,800 binary images were processed by all four OCR systems. All systems made approximately 40% more errors from images generated by Otsu`s method than those of the ideal histogram method. Two of the systems made approximately the same number of errors from images generated by the best fixed threshold value and Otsu`s method.

  2. Accelerated weight histogram method for exploring free energy landscapes

    NASA Astrophysics Data System (ADS)

    Lindahl, V.; Lidmar, J.; Hess, B.

    2014-07-01

    Calculating free energies is an important and notoriously difficult task for molecular simulations. The rapid increase in computational power has made it possible to probe increasingly complex systems, yet extracting accurate free energies from these simulations remains a major challenge. Fully exploring the free energy landscape of, say, a biological macromolecule typically requires sampling large conformational changes and slow transitions. Often, the only feasible way to study such a system is to simulate it using an enhanced sampling method. The accelerated weight histogram (AWH) method is a new, efficient extended ensemble sampling technique which adaptively biases the simulation to promote exploration of the free energy landscape. The AWH method uses a probability weight histogram which allows for efficient free energy updates and results in an easy discretization procedure. A major advantage of the method is its general formulation, making it a powerful platform for developing further extensions and analyzing its relation to already existing methods. Here, we demonstrate its efficiency and general applicability by calculating the potential of mean force along a reaction coordinate for both a single dimension and multiple dimensions. We make use of a non-uniform, free energy dependent target distribution in reaction coordinate space so that computational efforts are not wasted on physically irrelevant regions. We present numerical results for molecular dynamics simulations of lithium acetate in solution and chignolin, a 10-residue long peptide that folds into a β-hairpin. We further present practical guidelines for setting up and running an AWH simulation.

  3. Primary plasma cell leukemia: clinical, immunophenotypic, DNA ploidy, and cytogenetic characteristics.

    PubMed

    García-Sanz, R; Orfão, A; González, M; Tabernero, M D; Bladé, J; Moro, M J; Fernández-Calvo, J; Sanz, M A; Pérez-Simón, J A; Rasillo, A; Miguel, J F

    1999-02-01

    We report on a series of 26 patients diagnosed with primary (de novo) plasma cell (PC) leukemia (PCL) in whom we analyzed the clinicobiologic characteristics of the disease together with the immunophenotype, DNA cell content, proliferative index, and numeric chromosomal aberrations of the neoplastic PC, and compared them with 664 multiple myeloma (MM) patients at diagnosis. The median age, sex ratio, and bone lesion extension were similar, but PCL cases displayed a higher prevalence of clinical stage III, extramedullary involvement, and Bence Jones cases, with fewer IgA cases than for MM patients. In addition, according to several prognostic indicators (beta2-microglobulin serum level, proportion of S-phase PCs, proteinuria, calcium serum level, lactate dehydrogenase [LDH] and renal function), the incidence of adverse prognostic factors was significantly higher in PCL versus MM. Immunophenotypic expression was similar for CD38, CD138, CD2, CD3, CD16, CD10, CD13, and CD15, but PCL differed from MM in the expression of CD56, CD9 HLA-DR, CD117, and CD20 antigens. Twenty-two PCL cases were diploid and one was hypodiploid, while most MM cases (57%) showed DNA hyperdiploidy. With the fluorescent in situ hydridization (FISH) technique, 12 of 13 PCL cases displayed the numeric aberrations, -13 (86%), +/-1 (57%), +18 (43%), and -X in women (25%), but they lacked several numeric aberrations usually found in MM such as +3, +6, +9, +11, and +15. PCL cases had a lower overall response to therapy than MM cases (38% v 63%, P =.01332). Among PCL patients, a trend for a worse response was observed in cases treated with melphalan and prednisone (MP) versus polychemotherapy. Overall survival was significantly worse in PCL versus MM patients (8 v 36 months, P <.0001), but it was significantly better in PCL patients treated with polychemotherapy versus MP (18 v 3 months, P =.0137). By contrast, MM patients did not show significant differences in overall survival according to the

  4. Histogram flow mapping with optical coherence tomography for in vivo skin angiography of hereditary hemorrhagic telangiectasia

    PubMed Central

    Cheng, Kyle H. Y.; Mariampillai, Adrian; Lee, Kenneth K. C.; Vuong, Barry; Luk, Timothy W. H.; Ramjist, Joel; Curtis, Anne; Jakubovic, Henry; Kertes, Peter; Letarte, Michelle; Faughnan, Marie E.; HHT Investigator Group, Brain Vascular Malformation Consortium; Yang, Victor X. D.

    2014-01-01

    Abstract. Speckle statistics of flowing scatterers have been well documented in the literature. Speckle variance optical coherence tomography exploits the large variance values of intensity changes in time caused mainly by the random backscattering of light resulting from translational activity of red blood cells to map out the microvascular networks. A method to map out the microvasculature malformation of skin based on the time-domain histograms of individual pixels is presented with results obtained from both normal skin and skin containing vascular malformation. Results demonstrated that this method can potentially map out deeper blood vessels and enhance the visualization of microvasculature in low signal regions, while being resistant against motion (e.g., patient tremor or internal reflex movements). The overall results are manifested as more uniform en face projection maps of microvessels. Potential applications include clinical imaging of skin vascular abnormalities and wide-field skin angiography for the study of complex vascular networks. PMID:25140883

  5. Development of a Quality Assurance Procedure for Dose Volume Histogram Analysis

    NASA Astrophysics Data System (ADS)

    Davenport, David A.

    The role of the dose-volume histogram (DVH) is rapidly expanding in radiation oncology treatment planning. DVHs are already relied upon to differentiate between two similar plans and evaluate organ-at-risk dosage. Their role will become even more important as progress continues towards implementing biologically based treatment planning systems. Therefore it is imperative that the accuracy of DVHs is evaluated and reappraised after any major software or hardware upgrades, affecting a treatment planning system (TPS). The purpose of this work is to create and implement a comprehensive quality assurance procedure evaluating dose volume histograms to insure their accuracy while satisfying American College of Radiology guidelines. Virtual phantoms of known volumes were created in Pinnacle TPS and exposed to different beam arrangements. Variables including grid size and slice thickness were varied and their effects were analyzed. The resulting DVHs were evaluated by comparison to the commissioned percent depth dose values using a custom Excel spreadsheet. After determining the uncertainty of the DVH based on these variables, multiple second check calculations were performed using MIM Maestro and Matlab software packages. The uncertainties of the DVHs were shown to be less than +/- 3%. The average uncertainty was shown to be less than +/- 1%. The second check procedures resulted in mean percent differences less than 1% which confirms the accuracy of DVH calculation in Pinnacle and the effectiveness of the quality assurance template. The importance of knowing the limits of accuracy of the DVHs, which are routinely used to assess the quality of clinical treatment plans, cannot be overestimated. The developed comprehensive QA procedure evaluating the accuracy of the DVH statistical analysis will become a part of our clinical arsenal for periodic tests of the treatment planning system. It will also be performed at the time of commissioning and after any major software

  6. Identification of clinically important ascomycetous yeasts based on nucleotide divergence in the 5' end of the large-subunit (26S) ribosomal DNA gene.

    PubMed Central

    Kurtzman, C P; Robnett, C J

    1997-01-01

    Clinically important species of Candida and related organisms were compared for extent of nucleotide divergence in the 5' end of the large-subunit (26S) ribosomal DNA (rDNA) gene. This rDNA region is sufficiently variable to allow reliable separation of all known clinically significant yeast species. Of the 204 described species examined, 21 appeared to be synonyms of previously described organisms. Phylogenetic relationships among the species are presented. PMID:9114410

  7. An efficient Earth Mover's Distance algorithm for robust histogram comparison.

    PubMed

    Ling, Haibin; Okada, Kazunori

    2007-05-01

    We propose EMD-L1: a fast and exact algorithm for computing the Earth Mover's Distance (EMD) between a pair of histograms. The efficiency of the new algorithm enables its application to problems that were previously prohibitive due to high time complexities. The proposed EMD-L1 significantly simplifies the original linear programming formulation of EMD. Exploiting the L1 metric structure, the number of unknown variables in EMD-L1 is reduced to O(N) from O(N2) of the original EMD for a histogram with N bins. In addition, the number of constraints is reduced by half and the objective function of the linear program is simplified. Formally, without any approximation, we prove that the EMD-L1 formulation is equivalent to the original EMD with a L1 ground distance. To perform the EMD-L1 computation, we propose an efficient tree-based algorithm, Tree-EMD. Tree-EMD exploits the fact that a basic feasible solution of the simplex algorithm-based solver forms a spanning tree when we interpret EMD-L1 as a network flow optimization problem. We empirically show that this new algorithm has an average time complexity of O(N2), which significantly improves the best reported supercubic complexity of the original EMD. The accuracy of the proposed methods is evaluated by experiments for two computation-intensive problems: shape recognition and interest point matching using multidimensional histogram-based local features. For shape recognition, EMD-L1 is applied to compare shape contexts on the widely tested MPEG7 shape data set, as well as an articulated shape data set. For interest point matching, SIFT, shape context and spin image are tested on both synthetic and real image pairs with large geometrical deformation, illumination change, and heavy intensity noise. The results demonstrate that our EMD-L1-based solutions outperform previously reported state-of-the-art features and distance measures in solving the two tasks. PMID:17356203

  8. Shot-Noise Limited Single-Molecule FRET Histograms: Comparison between Theory and Experiments†

    PubMed Central

    Nir, Eyal; Michalet, Xavier; Hamadani, Kambiz M.; Laurence, Ted A.; Neuhauser, Daniel; Kovchegov, Yevgeniy; Weiss, Shimon

    2011-01-01

    We describe a simple approach and present a straightforward numerical algorithm to compute the best fit shot-noise limited proximity ratio histogram (PRH) in single-molecule fluorescence resonant energy transfer diffusion experiments. The key ingredient is the use of the experimental burst size distribution, as obtained after burst search through the photon data streams. We show how the use of an alternated laser excitation scheme and a correspondingly optimized burst search algorithm eliminates several potential artifacts affecting the calculation of the best fit shot-noise limited PRH. This algorithm is tested extensively on simulations and simple experimental systems. We find that dsDNA data exhibit a wider PRH than expected from shot noise only and hypothetically account for it by assuming a small Gaussian distribution of distances with an average standard deviation of 1.6 Å. Finally, we briefly mention the results of a future publication and illustrate them with a simple two-state model system (DNA hairpin), for which the kinetic transition rates between the open and closed conformations are extracted. PMID:17078646

  9. DNA methylation profiling identifies two splenic marginal zone lymphoma subgroups with different clinical and genetic features

    PubMed Central

    Arribas, Alberto J.; Rinaldi, Andrea; Mensah, Afua A.; Kwee, Ivo; Cascione, Luciano; Robles, Eloy F.; Martinez-Climent, Jose A.; Oscier, David; Arcaini, Luca; Baldini, Luca; Marasca, Roberto; Thieblemont, Catherine; Briere, Josette; Forconi, Francesco; Zamò, Alberto; Bonifacio, Massimiliano; Mollejo, Manuela; Facchetti, Fabio; Dirnhofer, Stephan; Ponzoni, Maurilio; Bhagat, Govind; Piris, Miguel A.; Gaidano, Gianluca; Zucca, Emanuele; Rossi, Davide

    2015-01-01

    Splenic marginal zone lymphoma is a rare lymphoma. Loss of 7q31 and somatic mutations affecting the NOTCH2 and KLF2 genes are the commonest genomic aberrations. Epigenetic changes can be pharmacologically reverted; therefore, identification of groups of patients with specific epigenomic alterations might have therapeutic relevance. Here we integrated genome-wide DNA-promoter methylation profiling with gene expression profiling, and clinical and biological variables. An unsupervised clustering analysis of a test series of 98 samples identified 2 clusters with different degrees of promoter methylation. The cluster comprising samples with higher-promoter methylation (High-M) had a poorer overall survival compared with the lower (Low-M) cluster. The prognostic relevance of the High-M phenotype was confirmed in an independent validation set of 36 patients. In the whole series, the High-M phenotype was associated with IGHV1-02 usage, mutations of NOTCH2 gene, 7q31-32 loss, and histologic transformation. In the High-M set, a number of tumor-suppressor genes were methylated and repressed. PRC2 subunit genes and several prosurvival lymphoma genes were unmethylated and overexpressed. A model based on the methylation of 3 genes (CACNB2, HTRA1, KLF4) identified a poorer-outcome patient subset. Exposure of splenic marginal zone lymphoma cell lines to a demethylating agent caused partial reversion of the High-M phenotype and inhibition of proliferation. PMID:25612624

  10. Variations in DNA subtype, antifungal susceptibility, and slime production among clinical isolates of Candida parapsilosis.

    PubMed

    Pfaller, M A; Messer, S A; Hollis, R J

    1995-01-01

    Candida parapsilosis is an important nosocomial pathogen that can proliferate in high concentrations of glucose and form biofilms on prosthetic materials. We investigated the genotypic diversity, slime production, and antifungal susceptibility among 60 isolates of C. parapsilosis from 44 patients and 10 patient care providers from five different medical centers. Molecular typing was performed using macrorestriction digest profiles with BssHII followed by pulsed-field gel electrophoresis (REAG) and by electrophoretic karyotyping (EK). Slime production was evaluated by growing the organisms in Sabouraud broth with 8% glucose and examining the walls of the tubes for the presence of an adherent slime layer. Antifungal susceptibility to amphotericin B, 5-fluorocytosine, fluconazole, and itraconazole was determined using National Committee for Clinical Laboratory Standards proposed standard methods. Overall 28 different DNA types were identified by REAG and EK methods. MIC90 values ranged from 0.12 microgram/ml for itraconazole to 1.0 microgram/ml for fluconazole and amphotericin B. Sixty-five percent of the isolates produced slime: 37% were moderately to strongly positive, 28% were weakly positive, and 35% were negative. Overall, 83% of blood and catheter isolates were slime positive versus 53% of isolates from all other sites (P < 0.05). These data underscore the genetic diversity and susceptibility of C. parapsilosis to antifungal agents. Slime production may be important in enabling C. parapsilosis to cause catheter-related bloodstream infections. PMID:7789100

  11. DNA methylation profiling identifies two splenic marginal zone lymphoma subgroups with different clinical and genetic features.

    PubMed

    Arribas, Alberto J; Rinaldi, Andrea; Mensah, Afua A; Kwee, Ivo; Cascione, Luciano; Robles, Eloy F; Martinez-Climent, Jose A; Oscier, David; Arcaini, Luca; Baldini, Luca; Marasca, Roberto; Thieblemont, Catherine; Briere, Josette; Forconi, Francesco; Zamò, Alberto; Bonifacio, Massimiliano; Mollejo, Manuela; Facchetti, Fabio; Dirnhofer, Stephan; Ponzoni, Maurilio; Bhagat, Govind; Piris, Miguel A; Gaidano, Gianluca; Zucca, Emanuele; Rossi, Davide; Bertoni, Francesco

    2015-03-19

    Splenic marginal zone lymphoma is a rare lymphoma. Loss of 7q31 and somatic mutations affecting the NOTCH2 and KLF2 genes are the commonest genomic aberrations. Epigenetic changes can be pharmacologically reverted; therefore, identification of groups of patients with specific epigenomic alterations might have therapeutic relevance. Here we integrated genome-wide DNA-promoter methylation profiling with gene expression profiling, and clinical and biological variables. An unsupervised clustering analysis of a test series of 98 samples identified 2 clusters with different degrees of promoter methylation. The cluster comprising samples with higher-promoter methylation (High-M) had a poorer overall survival compared with the lower (Low-M) cluster. The prognostic relevance of the High-M phenotype was confirmed in an independent validation set of 36 patients. In the whole series, the High-M phenotype was associated with IGHV1-02 usage, mutations of NOTCH2 gene, 7q31-32 loss, and histologic transformation. In the High-M set, a number of tumor-suppressor genes were methylated and repressed. PRC2 subunit genes and several prosurvival lymphoma genes were unmethylated and overexpressed. A model based on the methylation of 3 genes (CACNB2, HTRA1, KLF4) identified a poorer-outcome patient subset. Exposure of splenic marginal zone lymphoma cell lines to a demethylating agent caused partial reversion of the High-M phenotype and inhibition of proliferation. PMID:25612624

  12. DNA vaccines targeting human papillomavirus-associated diseases: progresses in animal and clinical studies

    PubMed Central

    Han, Kyusun Torque

    2013-01-01

    Human papillomavirus (HPV) infection is a major cause of cervical cancer and its precancerous diseases. Cervical cancer is the second deadliest cancer killer among women worldwide. Moreover, HPV is also known to be a causative agent of oral, pharyngeal, anal and genital cancer. Recent application of HPV structural protein (L1)-targeted prophylactic vaccines (Gardasil® and Cervarix®) is expected to reduce the incidence of HPV infection and cervical cancer, and possibly other HPV-associated cancers. However, the benefit of the prophylactic vaccines for treating HPV-infected patients is unlikely, underscoring the importance of developing therapeutic vaccines against HPV infection. In this regard, numerous types of therapeutic vaccine approaches targeting the HPV regulatory proteins, E6 and E7, have been tested for their efficacy in animals and clinically. In this communication, we review HPV vaccine types, in particular DNA vaccines, their designs and delivery by electroporation and their immunologic and antitumor efficacy in animals and humans, along with the basics of HPV and its pathogenesis. PMID:23858401

  13. Evolution of DNA aptamers for malignant brain tumor gliosarcoma cell recognition and clinical tissue imaging.

    PubMed

    Wu, Qiaoyi; Wu, Liang; Wang, Yuzhe; Zhu, Zhi; Song, Yanling; Tan, Yuyu; Wang, Xing-Fu; Li, Jiuxing; Kang, Dezhi; Yang, Chaoyong James

    2016-06-15

    Gliosarcoma, a variant of glioblastoma multiforme (GBM), is a highly invasive malignant tumor. Unfortunately, this disease still marked by poor prognosis regardless of modern treatments. It is of great significance to discover specific molecular probes targeting gliosarcoma for early cancer diagnosis and therapy. Herein, we have selected a group of DNA aptamers with high affinity and selectivity against gliosarcoma cells K308 using cell-SELEX. All the dissociation constants of these aptamers against gliosarcoma cells were in the nanomolar range and aptamer WQY-9 has the highest affinity and good selectivity among them. Furthermore, truncated aptamer sequence, WQY-9-B, shows similar recognition ability to aptamer WQY-9. In addition, WQY-9-B was found to be able to bind selectively and internalize into cytoplasm of target cancer cell at 37 °C. More importantly, compared to a random sequence, aptamer WQY-9-B showed excellent recognition rate (73.3%) for tissue sections of clinical gliosarcoma samples. These data suggests that aptamer WQY-9-B has excellent potential as an effective molecular probe for gliosarcoma diagnosis. PMID:26802746

  14. Implementing a 3D histogram version of the Energy-Test in ROOT

    NASA Astrophysics Data System (ADS)

    Cohen, E. O.; Reid, I. D.; Piasetzky, E.

    2016-08-01

    Comparing simulation and data histograms is of interest in nuclear and particle physics experiments; however, the leading three-dimensional histogram comparison tool available in ROOT, the 3D Kolmogorov-Smirnov test, exhibits shortcomings. Throughout the following, we present and discuss the implementation of an alternative comparison test for three-dimensional histograms, based on the Energy-Test by Aslan and Zech. The software package can be found at http://www-nuclear.tau.ac.il/ecohen/.

  15. Detection of varicella-zoster virus (VZV) DNA in clinical samples from patients with VZV by the polymerase chain reaction.

    PubMed Central

    Kido, S; Ozaki, T; Asada, H; Higashi, K; Kondo, K; Hayakawa, Y; Morishima, T; Takahashi, M; Yamanishi, K

    1991-01-01

    A polymerase chain reaction system for the detection of varicella-zoster virus was established. Of 25 nucleotides, 4 oligonucleotide pairs (regions of thymidine kinase, thymidylate synthetase, glycoprotein I, and immediate early gene) were synthesized. The first three oligonucleotide pairs could be used as primers on the basis of specific DNA amplification. Varicella-zoster virus DNA was amplified by this polymerase chain reaction system in 20 of 20 vesicle samples, 5 of 6 crusts, and 12 of 13 throat swabs collected from patients with clinical varicella. Images PMID:1847154

  16. Quantification of viral DNA during HIV-1 infection: A review of relevant clinical uses and laboratory methods.

    PubMed

    Alidjinou, E K; Bocket, L; Hober, D

    2015-02-01

    Effective antiretroviral therapy usually leads to undetectable HIV-1 RNA in the plasma. However, the virus persists in some cells of infected patients as various DNA forms, both integrated and unintegrated. This reservoir represents the greatest challenge to the complete cure of HIV-1 infection and its characteristics highly impact the course of the disease. The quantification of HIV-1 DNA in blood samples constitutes currently the most practical approach to measure this residual infection. Real-time quantitative PCR (qPCR) is the most common method used for HIV-DNA quantification and many strategies have been developed to measure the different forms of HIV-1 DNA. In the literature, several "in-house" PCR methods have been used and there is a need for standardization to have comparable results. In addition, qPCR is limited for the precise quantification of low levels by background noise. Among new assays in development, digital PCR was shown to allow an accurate quantification of HIV-1 DNA. Total HIV-1 DNA is most commonly measured in clinical routine. The absolute quantification of proviruses and unintegrated forms is more often used for research purposes. PMID:25201144

  17. Violence detection based on histogram of optical flow orientation

    NASA Astrophysics Data System (ADS)

    Yang, Zhijie; Zhang, Tao; Yang, Jie; Wu, Qiang; Bai, Li; Yao, Lixiu

    2013-12-01

    In this paper, we propose a novel approach for violence detection and localization in a public scene. Currently, violence detection is considerably under-researched compared with the common action recognition. Although existing methods can detect the presence of violence in a video, they cannot precisely locate the regions in the scene where violence is happening. This paper will tackle the challenge and propose a novel method to locate the violence location in the scene, which is important for public surveillance. The Gaussian Mixed Model is extended into the optical flow domain in order to detect candidate violence regions. In each region, a new descriptor, Histogram of Optical Flow Orientation (HOFO), is proposed to measure the spatial-temporal features. A linear SVM is trained based on the descriptor. The performance of the method is demonstrated on the publicly available data sets, BEHAVE and CAVIAR.

  18. Maximum-Likelihood Fits to Histograms for Improved Parameter Estimation

    NASA Astrophysics Data System (ADS)

    Fowler, J. W.

    2014-08-01

    Straightforward methods for adapting the familiar statistic to histograms of discrete events and other Poisson distributed data generally yield biased estimates of the parameters of a model. The bias can be important even when the total number of events is large. For the case of estimating a microcalorimeter's energy resolution at 6 keV from the observed shape of the Mn K fluorescence spectrum, a poor choice of can lead to biases of at least 10 % in the estimated resolution when up to thousands of photons are observed. The best remedy is a Poisson maximum-likelihood fit, through a simple modification of the standard Levenberg-Marquardt algorithm for minimization. Where the modification is not possible, another approach allows iterative approximation of the maximum-likelihood fit.

  19. Using histograms to introduce randomization in the generation of ensembles of decision trees

    DOEpatents

    Kamath, Chandrika; Cantu-Paz, Erick; Littau, David

    2005-02-22

    A system for decision tree ensembles that includes a module to read the data, a module to create a histogram, a module to evaluate a potential split according to some criterion using the histogram, a module to select a split point randomly in an interval around the best split, a module to split the data, and a module to combine multiple decision trees in ensembles. The decision tree method includes the steps of reading the data; creating a histogram; evaluating a potential split according to some criterion using the histogram, selecting a split point randomly in an interval around the best split, splitting the data, and combining multiple decision trees in ensembles.

  20. Custom IC/Embedded IP design for histogram in video processing application

    NASA Astrophysics Data System (ADS)

    Pandey, Manoj; Chaturvedi, Richa; Rai, S. K.

    2016-03-01

    Histogram is an integral part of video processing applications. Either of the design methods ASIC or Embedded, histogram computation is an important functional block. This paper proposes the custom Integrated Circuit (IC) as an ASIC and an embedded IP to compute the colored histogram function. Histogram computation has two features: color and spatial. Color feature has been calculated using find_bin and spatial feature is calculated using kernel function. The design is verified using NCSIM Cadence tool, while it is synthesized using RTL compiler. Finally, the embedded IP has interfaced with Kernel based mean shift algorithm in tracking a moving object and implemented on Xilinx Spartan 6 LX150T FPGA.

  1. Infrared image segmentation method based on spatial coherence histogram and maximum entropy

    NASA Astrophysics Data System (ADS)

    Liu, Songtao; Shen, Tongsheng; Dai, Yao

    2014-11-01

    In order to segment the target well and suppress background noises effectively, an infrared image segmentation method based on spatial coherence histogram and maximum entropy is proposed. First, spatial coherence histogram is presented by weighting the importance of the different position of these pixels with the same gray-level, which is obtained by computing their local density. Then, after enhancing the image by spatial coherence histogram, 1D maximum entropy method is used to segment the image. The novel method can not only get better segmentation results, but also have a faster computation time than traditional 2D histogram-based segmentation methods.

  2. Histogram Analysis of Gadoxetic Acid-Enhanced MRI for Quantitative Hepatic Fibrosis Measurement

    PubMed Central

    Kim, Honsoul; Park, Seong Ho; Kim, Eun Kyung; Kim, Myeong-Jin; Park, Young Nyun; Park, Hae-Jeong; Choi, Jin-Young

    2014-01-01

    Purpose The diagnosis and monitoring of liver fibrosis is an important clinical issue; however, this is usually achieved by invasive methods such as biopsy. We aimed to determine whether histogram analysis of hepatobiliary phase images of gadoxetic acid-enhanced magnetic resonance imaging (MRI) can provide non-invasive quantitative measurement of liver fibrosis. Methods This retrospective study was approved by the institutional ethics committee, and a waiver of informed consent was obtained. Hepatobiliary phase images of preoperative gadoxetic acid-enhanced MRI studies of 105 patients (69 males, 36 females; age 56.1±12.2) with pathologically documented liver fibrosis grades were analyzed. Fibrosis staging was F0/F1/F2/F3/F4 (METAVIR system) for 11/20/13/15/46 patients, respectively. Four regions-of-interest (ROI, each about 2 cm2) were placed on predetermined locations of representative images. The measured signal intensity of pixels in each ROI was used to calculate corrected coefficient of variation (cCV), skewness, and kurtosis. An average value of each parameter was calculated for comparison. Statistical analysis was performed by ANOVA, receiver operating characteristic (ROC) curve analysis, and linear regression. Results The cCV showed statistically significant differences among pathological fibrosis grades (P<0.001) whereas skewness and kurtosis did not. Univariable linear regression analysis suggested cCV to be a meaningful parameter in predicting the fibrosis grade (P<0.001, β = 0.40 and standard error  = 0.06). For discriminating F0-3 from F4, the area under ROC score was 0.857, standard deviation 0.036, 95% confidence interval 0.785–0.928. Conclusion Histogram analysis of hepatobiliary phase images of gadoxetic acid-enhanced MRI can provide non-invasive quantitative measurements of hepatic fibrosis. PMID:25460180

  3. Nonrigid registration of joint histograms for intensity standardization in magnetic resonance imaging.

    PubMed

    Jäger, Florian; Hornegger, Joachim

    2009-01-01

    A major disadvantage of magnetic resonance imaging (MRI) compared to other imaging modalities like computed tomography is the fact that its intensities are not standardized. Our contribution is a novel method for MRI signal intensity standardization of arbitrary MRI scans, so as to create a pulse sequence dependent standard intensity scale. The proposed method is the first approach that uses the properties of all acquired images jointly (e.g., T1- and T2-weighted images). The image properties are stored in multidimensional joint histograms. In order to normalize the probability density function (pdf) of a newly acquired data set, a nonrigid image registration is performed between a reference and the joint histogram of the acquired images. From this matching a nonparametric transformation is obtained, which describes a mapping between the corresponding intensity spaces and subsequently adapts the image properties of the newly acquired series to a given standard. As the proposed intensity standardization is based on the probability density functions of the data sets only, it is independent of spatial coherence or prior segmentations of the reference and current images. Furthermore, it is not designed for a particular application, body region or acquisition protocol. The evaluation was done using two different settings. First, MRI head images were used, hence the approach can be compared to state-of-the-art methods. Second, whole body MRI scans were used. For this modality no other normalization algorithm is known in literature. The Jeffrey divergence of the pdfs of the whole body scans was reduced by 45%. All used data sets were acquired during clinical routine and thus included pathologies. PMID:19116196

  4. Development & evaluation of biotinylated DNA probe for clinical diagnosis of chikungunya infection in patients’ acute phase serum & CSF samples

    PubMed Central

    Kumar, Jyoti S.; Parida, Manmohan; Lakshmana Rao, P.V.

    2013-01-01

    Background & objectives: The resurgence of chikungunya virus (CHIKV) in the Indian Ocean Islands and India has drawn worldwide attention due to its explosive nature, high morbidity and complex clinico-pathological manifestations. The early confirmatory diagnosis of CHIKV is essential for management as well as control of unprecedented epidemics. The present study describes the development and evaluation of a highly sensitive and specific E1 structural gene specific biotinylated DNA probe for detection of chikungunya virus in clinical samples using a dot blot format. Methods: The complementary DNA (cDNA) of CHIKV was spotted on to nylon membrane. The membrane was subjected to prehybridization and hybridization and developed using a colour development solution containing DAB chromogen. Results: The CHIKV E1 specific DNA probe was highly sensitive detecting picogram levels of target nucleic acid. The comparative evaluation with SYBR Green I based real-time RT-PCR revealed 99 per cent accordance with a sensitivity and specificity of 99 and 98 per cent, respectively. The specificity of this assay was further confirmed through cross-reaction studies with confirmed dengue and Japanese encephalitis (JE) patient serum samples along with infected culture supernatant of Ross River and Saint Louis encephalitis and plasmid DNA of O’Nyong Nyong, Semlinki forest and Sindbis viruses. Interpretation & conclusion: The DNA probe reported in this study may be useful for specific, sensitive and confirmatory clinical diagnosis of chikungunya infection in acute phase human patient serum and CSF samples. This assay can also be used in the laboratory for quantification of viral antigen in cell culture supernatant for research purpose. PMID:24056565

  5. Methanol-based fixation is superior to buffered formalin for next-generation sequencing of DNA from clinical cancer samples

    PubMed Central

    Piskorz, A. M.; Ennis, D.; Macintyre, G.; Goranova, T. E.; Eldridge, M.; Segui-Gracia, N.; Valganon, M.; Hoyle, A.; Orange, C.; Moore, L.; Jimenez-Linan, M.; Millan, D.; McNeish, I. A.; Brenton, J. D.

    2016-01-01

    Background Next-generation sequencing (NGS) of tumour samples is a critical component of personalised cancer treatment, but it requires high-quality DNA samples. Routine neutral-buffered formalin (NBF) fixation has detrimental effects on nucleic acids, causing low yields, as well as fragmentation and DNA base changes, leading to significant artefacts. Patients and methods We have carried out a detailed comparison of DNA quality from matched samples isolated from high-grade serous ovarian cancers from 16 patients fixed in methanol and NBF. These experiments use tumour fragments and mock biopsies to simulate routine practice, ensuring that results are applicable to standard clinical biopsies. Results Using matched snap-frozen tissue as gold standard comparator, we show that methanol-based fixation has significant benefits over NBF, with greater DNA yield, longer fragment size and more accurate copy-number calling using shallow whole-genome sequencing (WGS). These data also provide a new approach to understand and quantify artefactual effects of fixation using non-negative matrix factorisation to analyse mutational spectra from targeted and WGS data. Conclusion We strongly recommend the adoption of methanol fixation for sample collection strategies in new clinical trials. This approach is immediately available, is logistically simple and can offer cheaper and more reliable mutation calling than traditional NBF fixation. PMID:26681675

  6. Analysis of RapidArc optimization strategies using objective function values and dose-volume histograms.

    PubMed

    Oliver, Michael; Gagne, Isabelle; Popescu, Carmen; Ansbacher, Will; Beckham, Wayne A

    2010-01-01

    RapidArc is a novel treatment planning and delivery system that has recently been made available for clinical use. Included within the Eclipse treatment planning system are a number of different optimization strategies that can be employed to improve the quality of the final treatment plan. The purpose of this study is to systematically assess three categories of strategies for four phantoms, and then apply proven strategies to clinical head and neck cases. Four phantoms were created within Eclipse with varying shapes and locations for the planning target volumes and organs at risk. A baseline optimization consisting of a single 359.8 degrees arc with collimator at 45 degrees was applied to all phantoms. Three categories of strategies were assessed and compared to the baseline strategy. They include changing the initialization parameters, increasing the total number of control points, and increasing the total optimization time. Optimization log files were extracted from the treatment planning system along with final dose-volume histograms for plan assessment. Treatment plans were also generated for four head and neck patients to determine whether the results for phantom plans can be extended to clinical plans. The strategies that resulted in a significant difference from baseline were: changing the maximum leaf speed prior to optimization ( p < 0.05), increasing the total number of segments by adding an arc ( p < 0.05), and increasing the total optimization time by either continuing the optimization ( p < 0.01) or adding time to the optimization by pausing the optimization ( p < 0.01). The reductions in objective function values correlated with improvements in the dose-volume histogram (DVH). The addition of arcs and pausing strategies were applied to head and neck cancer cases, which demonstrated similar benefits with respect to the final objective function value and DVH. Analysis of the optimization log files is a useful way to intercompare treatment plans that

  7. Towards clinical application of pronuclear transfer to prevent mitochondrial DNA disease.

    PubMed

    Hyslop, Louise A; Blakeley, Paul; Craven, Lyndsey; Richardson, Jessica; Fogarty, Norah M E; Fragouli, Elpida; Lamb, Mahdi; Wamaitha, Sissy E; Prathalingam, Nilendran; Zhang, Qi; O'Keefe, Hannah; Takeda, Yuko; Arizzi, Lucia; Alfarawati, Samer; Tuppen, Helen A; Irving, Laura; Kalleas, Dimitrios; Choudhary, Meenakshi; Wells, Dagan; Murdoch, Alison P; Turnbull, Douglass M; Niakan, Kathy K; Herbert, Mary

    2016-06-16

    Mitochondrial DNA (mtDNA) mutations are maternally inherited and are associated with a broad range of debilitating and fatal diseases. Reproductive technologies designed to uncouple the inheritance of mtDNA from nuclear DNA may enable affected women to have a genetically related child with a greatly reduced risk of mtDNA disease. Here we report the first preclinical studies on pronuclear transplantation (PNT). Surprisingly, techniques used in proof-of-concept studies involving abnormally fertilized human zygotes were not well tolerated by normally fertilized zygotes. We have therefore developed an alternative approach based on transplanting pronuclei shortly after completion of meiosis rather than shortly before the first mitotic division. This promotes efficient development to the blastocyst stage with no detectable effect on aneuploidy or gene expression. After optimization, mtDNA carryover was reduced to <2% in the majority (79%) of PNT blastocysts. The importance of reducing carryover to the lowest possible levels is highlighted by a progressive increase in heteroplasmy in a stem cell line derived from a PNT blastocyst with 4% mtDNA carryover. We conclude that PNT has the potential to reduce the risk of mtDNA disease, but it may not guarantee prevention. PMID:27281217

  8. Preparation of Concentrated Chitosan/DNA Nanoparticle Formulations by Lyophilization for Gene Delivery at Clinically Relevant Dosages.

    PubMed

    Veilleux, Daniel; Nelea, Monica; Biniecki, Kristof; Lavertu, Marc; Buschmann, Michael D

    2016-01-01

    Chitosan/DNA polyplexes have been optimized for efficient and safe in vitro and in vivo gene delivery. Clinical application of this technology requires the development of formulations with higher concentrations to reach therapeutic dosages. Polyplexes were prepared using chitosan and EGFPLuc plasmids. Freeze-thawing and freeze-drying studies were performed to identify and optimize lyoprotectant and buffer contents in formulations. Freeze-dried samples were rehydrated in reduced volumes to increase their final DNA dose. Nanoparticle physicochemical properties were analyzed, and their transfection efficiency and cytotoxicity were measured in human embryonic kidney 293 cells. Data showed that 3.5 mM histidine buffer (pH 6.5) combined with one of 0.5% wt/vol sucrose, dextran 5 kDa, or trehalose was required to prevent polyplex aggregation during freeze-drying. Optimal formulations could be concentrated 20-fold, to a clinically desired ∼1 mg of DNA/mL, while maintaining near physiological pH and tonicity. Polyplexes were predominantly spherical, with diameters below 200 nm, polydispersity indexes below 0.32, and zeta potentials above +19 mV. Rehydrated formulations had transfection efficiencies no less than 65% of fresh polyplexes without excipients and had no effect on viability and metabolic activity of human embryonic kidney 293 cells. These concentrated formulations represent an important step toward clinical use of chitosan-based gene delivery systems. PMID:26852843

  9. 16S Ribosomal DNA Sequence Analysis of a Large Collection of Environmental and Clinical Unidentifiable Bacterial Isolates

    PubMed Central

    Drancourt, Michel; Bollet, Claude; Carlioz, Antoine; Martelin, Rolland; Gayral, Jean-Pierre; Raoult, Didier

    2000-01-01

    Some bacteria are difficult to identify with phenotypic identification schemes commonly used outside reference laboratories. 16S ribosomal DNA (rDNA)-based identification of bacteria potentially offers a useful alternative when phenotypic characterization methods fail. However, as yet, the usefulness of 16S rDNA sequence analysis in the identification of conventionally unidentifiable isolates has not been evaluated with a large collection of isolates. In this study, we evaluated the utility of 16S rDNA sequencing as a means to identify a collection of 177 such isolates obtained from environmental, veterinary, and clinical sources. For 159 isolates (89.8%) there was at least one sequence in GenBank that yielded a similarity score of ≥97%, and for 139 isolates (78.5%) there was at least one sequence in GenBank that yielded a similarity score of ≥99%. These similarity score values were used to defined identification at the genus and species levels, respectively. For isolates identified to the species level, conventional identification failed to produce accurate results because of inappropriate biochemical profile determination in 76 isolates (58.7%), Gram staining in 16 isolates (11.6%), oxidase and catalase activity determination in 5 isolates (3.6%) and growth requirement determination in 2 isolates (1.5%). Eighteen isolates (10.2%) remained unidentifiable by 16S rDNA sequence analysis but were probably prototype isolates of new species. These isolates originated mainly from environmental sources (P = 0.07). The 16S rDNA approach failed to identify Enterobacter and Pantoea isolates to the species level (P = 0.04; odds ratio = 0.32 [95% confidence interval, 0.10 to 1.14]). Elsewhere, the usefulness of 16S rDNA sequencing was compromised by the presence of 16S rDNA sequences with >1% undetermined positions in the databases. Unlike phenotypic identification, which can be modified by the variability of expression of characters, 16S rDNA sequencing provides

  10. Aeromonas jandaei (formerly genospecies DNA group 9 A. sobria), a new sucrose-negative species isolated from clinical specimens.

    PubMed Central

    Carnahan, A; Fanning, G R; Joseph, S W

    1991-01-01

    A large numerical taxonomy study conducted in 1988 of 165 mostly clinical Aeromonas strains from diverse geographic sources produced a cluster (S = 84%, SSM) of four sucrose-negative strains that included the DNA definition strain for DNA group 9 A. sobria (CDC 0787-80). These four strains, together with five additional strains received in 1989, were subjected to DNA-DNA hybridization (hydroxyapatite, 32P, 60 and 75 degrees C), and all eight strains were closely related to the ninth labeled DNA group 9 definition strain CDC 0787-80 (73 to 86% relatedness at 60 degrees C and 68 to 80% relatedness at 75 degrees C; percent divergence, 2.0 to 3.5). Type strains and DNA definition strains for all other established Aeromonas species were only 35 to 72% related (60 degrees C) to CDC 0787-80. We propose the name Aeromonas jandaei for this highly related group of nine strains, formerly known as DNA group 9 A. sobria. The type strain was designated ATCC 49568 (CDC 0787-80). The nine strains were examined at 36 degrees C and were found to be resistant to 0/129 (vibriostatic agent) and uniformly positive for oxidase, gas production from glucose, indole, lysine decarboxylase, arginine dihydrolase, o-nitrophenyl-beta-D-galactopyranoside, motility (25 degrees C), nitrate reduction, citrate utilization, hemolysis on sheep blood agar, and growth in Trypticase soy broth with no added NaCl. They all fermented D-glucose, D-mannitol, and mannose but did not ferment sucrose, cellobiose, L-arabinose, inositol, salicin, or D-sorbitol. They were uniformly negative for esculin and urea hydrolysis, elastase production, ornithine decarboxylation, and the string test. The antibiogram of A. jandaei resembled that of other aeromonads (resistance to ampicillin and cephalothin), but it differed from most other aeromonads because of resistance to single dilution of colistin and differed from clinical A. veronii biogroup sorbria (formerly A. sobria) by its nearly uniform resistance to cephalothin

  11. Do you need to compare two histograms not only by eye?

    NASA Astrophysics Data System (ADS)

    Cardiel, N.

    2015-05-01

    Although the use of histograms implies loss of information due to the fact that the actual data are replaced by the central values of the considered intervals, this graphical representation is commonly employed in scientific communication, particularly in Astrophysics. Sometimes this kind of comparison is unavoidable when one needs to compare new results with already published data only available in histogram format. Unfortunately, it is not infrequent to find in the literature examples of histogram comparisons where the similarity between the histograms is not statistically quantified but simply justified or discarded ``by eye''. In this poster several methods to quantify the similarity between two histograms are discussed. The availability of statistical packages, such as R (R Core Team 2014, R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing, Vienna, Austria. URL http://www.R-project.org/), notably simplify the understanding of the different approaches through the use of numerical simulations.

  12. Time-cumulated visible and infrared radiance histograms used as descriptors of surface and cloud variations

    NASA Technical Reports Server (NTRS)

    Seze, Genevieve; Rossow, William B.

    1991-01-01

    The spatial and temporal stability of the distributions of satellite-measured visible and infrared radiances, caused by variations in clouds and surfaces, are investigated using bidimensional and monodimensional histograms and time-composite images. Similar analysis of the histograms of the original and time-composite images provides separation of the contributions of the space and time variations to the total variations. The variability of both the surfaces and clouds is found to be larger at scales much larger than the minimum resolved by satellite imagery. This study shows that the shapes of these histograms are distinctive characteristics of the different climate regimes and that particular attributes of these histograms can be related to several general, though not universal, properties of clouds and surface variations at regional and synoptic scales. There are also significant exceptions to these relationships in particular climate regimes. The characteristics of these radiance histograms provide a stable well defined descriptor of the cloud and surface properties.

  13. Validation for clinical use of, and initial clinical experience with, a novel approach to population-based carrier screening using high-throughput, next-generation DNA sequencing.

    PubMed

    Hallam, Stephanie; Nelson, Heather; Greger, Valerie; Perreault-Micale, Cynthia; Davie, Jocelyn; Faulkner, Nicole; Neitzel, Dana; Casey, Kristie; Umbarger, Mark A; Chennagiri, Niru; Kramer, Alexander C; Porreca, Gregory J; Kennedy, Caleb J

    2014-03-01

    Traditional carrier screening assays are designed to look for only the most common mutations within a gene owing to cost considerations. Although this can yield high detection rates in specific populations for specific genes (such as cystic fibrosis in Caucasians), they are suboptimal for other ethnicities or for patients of mixed or unknown ethnic background. Next-generation DNA sequencing provides an opportunity to provide carrier screening using more comprehensive mutation panels that are limited primarily by information about the clinical impact of detected sequence changes. We describe a next-generation DNA sequencing-based assay capable of reliably screening patient samples in a timely and comprehensive manner. The analytic accuracy in a research setting has been documented. Here, we describe the additional studies performed to ensure the accuracy (analytic validity) and robustness of our assay for use in clinical practice and provide data from our experience offering this testing. Our clinical experience using this approach to screen 11,691 in vitro fertilization patients has identified 449 mutant alleles: 447 in carriers and 2 in an affected individual. In total, we found 87 distinct mutations in 14 different genes. Approximately one quarter of the mutations found are not included in traditional, limited, mutation panels, including 16 known mutations unique to our panel, and novel truncating mutations in several genes. PMID:24374108

  14. Landmark Detection in Orbital Images Using Salience Histograms

    NASA Technical Reports Server (NTRS)

    Wagstaff, Kiri L.; Panetta, Julian; Schorghofer, Norbert; Greeley, Ronald; PendletonHoffer, Mary; bunte, Melissa

    2010-01-01

    NASA's planetary missions have collected, and continue to collect, massive volumes of orbital imagery. The volume is such that it is difficult to manually review all of the data and determine its significance. As a result, images are indexed and searchable by location and date but generally not by their content. A new automated method analyzes images and identifies "landmarks," or visually salient features such as gullies, craters, dust devil tracks, and the like. This technique uses a statistical measure of salience derived from information theory, so it is not associated with any specific landmark type. It identifies regions that are unusual or that stand out from their surroundings, so the resulting landmarks are context-sensitive areas that can be used to recognize the same area when it is encountered again. A machine learning classifier is used to identify the type of each discovered landmark. Using a specified window size, an intensity histogram is computed for each such window within the larger image (sliding the window across the image). Next, a salience map is computed that specifies, for each pixel, the salience of the window centered at that pixel. The salience map is thresholded to identify landmark contours (polygons) using the upper quartile of salience values. Descriptive attributes are extracted for each landmark polygon: size, perimeter, mean intensity, standard deviation of intensity, and shape features derived from an ellipse fit.

  15. Wireless Micro-Ball endoscopic image enhancement using histogram information.

    PubMed

    Attar, Abdolrahman; Xie, Xiang; Zhang, Chun; Wang, Zhihua; Yue, Shigang

    2014-01-01

    Wireless endoscopy systems is a new innovative method widely used for gastrointestinal tract examination in recent decade. Wireless Micro-Ball endoscopy system with multiple image sensors is the newest proposed method which can make a full view image of the gastrointestinal tract. But still the quality of images from this new wireless endoscopy system is not satisfactory. It's hard for doctors and specialist to easily examine and interpret the captured images. The image features also are not distinct enough to be used for further processing. So as to enhance these low-contrast endoscopic images a new image enhancement method based on the endoscopic images features and color distribution is proposed in this work. The enhancement method is performed on three main steps namely color space transformation, edge preserving mask formation, and histogram information correction. The luminance component of CIE Lab, YCbCr, and HSV color space is enhanced in this method and then two other components added finally to form an enhanced color image. The experimental result clearly show the robustness of the method. PMID:25570705

  16. Lung Cancer Prediction Using Neural Network Ensemble with Histogram of Oriented Gradient Genomic Features

    PubMed Central

    Adetiba, Emmanuel; Olugbara, Oludayo O.

    2015-01-01

    This paper reports an experimental comparison of artificial neural network (ANN) and support vector machine (SVM) ensembles and their “nonensemble” variants for lung cancer prediction. These machine learning classifiers were trained to predict lung cancer using samples of patient nucleotides with mutations in the epidermal growth factor receptor, Kirsten rat sarcoma viral oncogene, and tumor suppressor p53 genomes collected as biomarkers from the IGDB.NSCLC corpus. The Voss DNA encoding was used to map the nucleotide sequences of mutated and normal genomes to obtain the equivalent numerical genomic sequences for training the selected classifiers. The histogram of oriented gradient (HOG) and local binary pattern (LBP) state-of-the-art feature extraction schemes were applied to extract representative genomic features from the encoded sequences of nucleotides. The ANN ensemble and HOG best fit the training dataset of this study with an accuracy of 95.90% and mean square error of 0.0159. The result of the ANN ensemble and HOG genomic features is promising for automated screening and early detection of lung cancer. This will hopefully assist pathologists in administering targeted molecular therapy and offering counsel to early stage lung cancer patients and persons in at risk populations. PMID:25802891

  17. Clinical application of DNA ploidy to cervical cancer screening: A review

    PubMed Central

    Garner, David

    2014-01-01

    Screening for cervical cancer with DNA ploidy assessment by automated quantitative image cytometry has spread throughout China over the past decade and now an estimated 1 million tests per year are done there. Compared to conventional liquid based cytology, DNA ploidy has competitive accuracy with much higher throughput per technician. DNA ploidy has the enormous advantage that it is an objective technology that can be taught in typically 2 or 3 wk, unlike qualitative cytology, and so it can enable screening in places that lack sufficient qualified cytotechnologists and cytopathologists for conventional cytology. Most papers on experience with application of the technology to cervical cancer screening over the past decade were published in the Chinese language. This review aims to provide a consistent framework for analysis of screening data and to summarize some of the work published from 2005 to the end of 2013. Of particular interest are a few studies comparing DNA ploidy with testing for high risk human papilloma virus (hrHPV) which suggest that DNA ploidy is at least equivalent, easier and less expensive than hrHPV testing. There may also be patient management benefits to combining hrHPV testing with DNA ploidy. Some knowledge gaps are identified and some suggestions are made for future research directions. PMID:25493231

  18. Intra-Gene DNA Methylation Variability Is a Clinically Independent Prognostic Marker in Women’s Cancers

    PubMed Central

    Bartlett, Thomas E.; Jones, Allison; Goode, Ellen L.; Fridley, Brooke L.; Cunningham, Julie M.; Berns, Els M. J. J.; Wik, Elisabeth; Salvesen, Helga B.; Davidson, Ben; Trope, Claes G.; Lambrechts, Sandrina; Vergote, Ignace; Widschwendter, Martin

    2015-01-01

    We introduce a novel per-gene measure of intra-gene DNA methylation variability (IGV) based on the Illumina Infinium HumanMethylation450 platform, which is prognostic independently of well-known predictors of clinical outcome. Using IGV, we derive a robust gene-panel prognostic signature for ovarian cancer (OC, n = 221), which validates in two independent data sets from Mayo Clinic (n = 198) and TCGA (n = 358), with significance of p = 0.004 in both sets. The OC prognostic signature gene-panel is comprised of four gene groups, which represent distinct biological processes. We show the IGV measurements of these gene groups are most likely a reflection of a mixture of intra-tumour heterogeneity and transcription factor (TF) binding/activity. IGV can be used to predict clinical outcome in patients individually, providing a surrogate read-out of hard-to-measure disease processes. PMID:26629914

  19. From sample to PCR product in under 45 minutes: a polymeric integrated microdevice for clinical and forensic DNA analysis.

    PubMed

    Lounsbury, Jenny A; Karlsson, Anne; Miranian, Daniel C; Cronk, Stephen M; Nelson, Daniel A; Li, Jingyi; Haverstick, Doris M; Kinnon, Paul; Saul, David J; Landers, James P

    2013-04-01

    The extraction and amplification of DNA from biological samples is laborious and time-consuming, requiring numerous instruments and sample handling steps. An integrated, single-use, poly(methyl methacrylate) (PMMA) microdevice for DNA extraction and amplification would benefit clinical and forensic communities, providing a completely closed system with rapid sample-in-PCR-product-out capability. Here, we show the design and simple flow control required for enzyme-based DNA preparation and PCR from buccal swabs or liquid whole blood samples with an ~5-fold reduction in time. A swab containing cells or DNA could be loaded into a novel receptacle together with the DNA liberation reagents, heated using an infrared heating system, mixed with PCR reagents for one of three different target sets under syringe-driven flow, and thermally-cycled in less than 45 min, an ~6-fold reduction in analysis time as compared to conventional methods. The 4 : 1 PCR reagents : DNA ratio required to provide the correct final concentration of all PCR components for effective amplification was verified using image analysis of colored dyes in the PCR chamber. Novel single-actuation, 'normally-open' adhesive valves were shown to effectively seal the PCR chamber during thermal cycling, preventing air bubble expansion. The effectiveness of the device was demonstrated using three target sets: the sex-typing gene Amelogenin, co-amplification of the β-globin and gelsolin genes, and the amplification of 15 short tandem repeat (STR) loci plus Amelogenin. The use of the integrated microdevice was expanded to the analysis of liquid blood samples which, when incubated with the DNA liberation reagents, form a brown precipitate that inhibits PCR. A simple centrifugation of the integrated microchips (on a custom centrifuge), mobilized the precipitate away from the microchannel entrance, improving amplification of the β-globin and gelsolin gene fragments by ~6-fold. This plastic integrated microdevice

  20. Identification of ssDNA aptamers specific to clinical isolates of Streptococcus mutans strains with different cariogenicity.

    PubMed

    Cui, Wei; Liu, Jiaojiao; Su, Donghua; Hu, Danyang; Hou, Shuai; Hu, Tongnan; Yang, Jiyong; Luo, Yanping; Xi, Qing; Chu, Bingfeng; Wang, Chenglong

    2016-06-01

    Streptococcus mutans, a Gram-positive facultative anaerobic bacterium, is considered to be a major etiological factor for dental caries. In this study, plaques from dental enamel surfaces of caries-active and caries-free individuals were obtained and cultivated for S. mutans isolation. Morphology examination, biochemical characterization, and polymerase chain reaction were performed to identify S. mutans The cariogenicity of S. mutans strains isolated from clinical specimens was evaluated by testing the acidogenicity, aciduricity, extracellular polysaccharide production, and adhesion ability of the bacteria. Finally, subtractive SELEX (systematic evolution of ligands by exponential enrichment) technology targeting whole intact cells was used to screen for ssDNA aptamers specific to the strains with high cariogenicity. After nine rounds of subtractive SELEX, sufficient pool enrichment was achieved as shown by radioactive isotope analysis. The enriched pool was cloned and sequenced randomly, followed by MEME online and RNA structure software analysis of the sequences. Results from the flow cytometry indicated that aptamers H1, H16, H4, L1, L10, and H19 could discriminate highly cariogenic S. mutans strains from poorly cariogenic strains. Among these, Aptamer H19 had the strongest binding capacity with cariogenic S. mutans strains with a dissociation constant of 69.45 ± 38.53 nM. In conclusion, ssDNA aptamers specific to highly cariogenic clinical S. mutans strains were successfully obtained. These ssDNA aptamers might be used for the early diagnosis and treatment of dental caries. PMID:27151293

  1. Semen Quality and Sperm DNA Damage in Relation to Urinary Bisphenol A among Men from an Infertility Clinic

    PubMed Central

    Meeker, John D.; Ehrlich, Shelley; Toth, Thomas L.; Wright, Diane L.; Calafat, Antonia M.; Trisini, Ana T.; Ye, Xiaoyun; Hauser, Russ

    2010-01-01

    Bisphenol A (BPA) impairs spermatogenesis in animals, but human studies are lacking. We measured urinary BPA concentrations, semen quality, and sperm DNA damage (comet assay) in 190 men recruited through an infertility clinic. BPA was detected in 89% of samples, with a median (interquartile range [IQR]) concentration of 1.3 (0.8 – 2.5) ng/mL. Urinary BPA concentration was associated with slightly elevated, though not statistically significant, odds for below reference sperm concentration, motility, and morphology. When modeled as continuous dependent variables, an IQR increase in urinary BPA concentration was associated with declines in sperm concentration, motility, and morphology of 23% (95%CI –40%, -0.3%), 7.5% (-17%, +1.5%), and 13% (-26%, -0.1%), respectively, along with a 10% (0.03%, 19%) increase in sperm DNA damage measured as the percentage of DNA in comet tail. In conclusion, urinary BPA may be associated with declined semen quality and increased sperm DNA damage, but confirmatory studies are needed. PMID:20656017

  2. Using the Bootstrap Method for a Statistical Significance Test of Differences between Summary Histograms

    NASA Technical Reports Server (NTRS)

    Xu, Kuan-Man

    2006-01-01

    A new method is proposed to compare statistical differences between summary histograms, which are the histograms summed over a large ensemble of individual histograms. It consists of choosing a distance statistic for measuring the difference between summary histograms and using a bootstrap procedure to calculate the statistical significance level. Bootstrapping is an approach to statistical inference that makes few assumptions about the underlying probability distribution that describes the data. Three distance statistics are compared in this study. They are the Euclidean distance, the Jeffries-Matusita distance and the Kuiper distance. The data used in testing the bootstrap method are satellite measurements of cloud systems called cloud objects. Each cloud object is defined as a contiguous region/patch composed of individual footprints or fields of view. A histogram of measured values over footprints is generated for each parameter of each cloud object and then summary histograms are accumulated over all individual histograms in a given cloud-object size category. The results of statistical hypothesis tests using all three distances as test statistics are generally similar, indicating the validity of the proposed method. The Euclidean distance is determined to be most suitable after comparing the statistical tests of several parameters with distinct probability distributions among three cloud-object size categories. Impacts on the statistical significance levels resulting from differences in the total lengths of satellite footprint data between two size categories are also discussed.

  3. RHINO: Real-time histogram interpretation of numerical observations

    NASA Astrophysics Data System (ADS)

    Chandler, Susan; Lukesh, Gordon

    2006-05-01

    RHINO, Real-time Histogram Interpretation of Numerical Observations, is a specialty algorithm and tool under development for the United States Air Force Office of Scientific Research (AFOSR). The intent is to provide real-time feedback for adaptive control of telescope pointing for ground-space-ground laser illumination experiments. Nukove together with New Mexico State University first established a proof-of-principle laboratory experiment using RHINO and, under a controlled environment, reduction of the pointing error known as boresight was demonstrated. RHINO is resilient to effects such as glints, speckle, and scintillation. The forthcoming commercially available version of RHINO will use real-time field data and provide adaptive control to the user. The utility of RHINO is evident in a realistic scenario: Consider a space asset that has been joined by a microsat, perhaps 0.5m in size. The microsat may have been launched to simply listen in from close proximity, monitor the asset, image the asset or most critically, cause damage to the asset. If the goal is to destroy the microsat by long-range illumination with a high power laser and the microsat is meters from the asset (μrads at 1Mm) laser pointing is of utmost importance as the goal is certainly not to damage the space asset. RHINO offers the capability to estimate key metrics of laser system pointing, known as jitter and boresight. The algorithms used have been under development for nearly a decade, have been established in a laboratory environment, and have been tested with field data.

  4. Preference for luminance histogram regularities in natural scenes.

    PubMed

    Graham, Daniel; Schwarz, Bianca; Chatterjee, Anjan; Leder, Helmut

    2016-03-01

    Natural scene luminance distributions typically have positive skew, and for single objects, there is evidence that higher skew is a correlate (but not a guarantee) of glossiness. Skewness is also relevant to aesthetics: preference for glossy single objects (with high skew) has been shown even in infants, and skewness is a good predictor of fruit freshness. Given that primate vision appears to efficiently encode natural scene luminance variation, and given evidence that natural scene regularities may be a prerequisite for aesthetic perception in the spatial domain, here we ask whether humans in general prefer natural scenes with more positively skewed luminance distributions. If humans generally prefer images with the higher-order regularities typical of natural scenes and/or shiny objects, we would expect this to be the case. By manipulating luminance distribution skewness (holding mean and variance constant) for individual natural images, we show that in fact preference varies inversely with increasing positive skewness. This finding holds for: artistic landscape images and calibrated natural scenes; scenes with and without glossy surfaces; landscape scenes and close-up objects; and noise images with natural luminance histograms. Across conditions, humans prefer images with skew near zero over higher skew images, and they prefer skew lower than that of the unmodified scenes. These results suggest that humans prefer images with luminances that are distributed relatively evenly about the mean luminance, i.e., images with similar amounts of light and dark. We propose that our results reflect an efficient processing advantage of low-skew images over high-skew images, following evidence from prior brain imaging results. PMID:25872178

  5. Compressed histogram attribute profiles for the classification of VHR remote sensing images

    NASA Astrophysics Data System (ADS)

    Battiti, Romano; Demir, Begüm; Bruzzone, Lorenzo

    2015-10-01

    This paper presents a novel compressed histogram attribute profile (CHAP) for classification of very high resolution remote sensing images. The CHAP characterizes the marginal local distribution of attribute filter responses to model the texture information of each sample with a small number of image features. This is achieved based on a three steps algorithm. The first step is devoted to provide a complete characterization of spatial properties of objects in a scene. To this end, the attribute profile (AP) is initially built by the sequential application of attribute filters to the considered image. Then, to capture complete spatial characteristics of the structures in the scene a local histogram is calculated for each sample of each image in the AP. The local histograms of the same pixel location can contain redundant information since: i) adjacent histogram bins can provide similar information; and ii) the attributes obtained with similar attribute filter threshold values lead to redundant features. In the second step, to point out the redundancies the local histograms of the same pixel locations in the AP are organized into a 2D matrix representation, where columns are associated to the local histograms and rows represents a specific bin in all histograms of the considered sequence of filtered attributes in the profile. This representation results in the characterization of the texture information of each sample through a 2D texture descriptor. In the final step, a novel compression approach based on a uniform 2D quantization strategy is applied to remove the redundancy of the 2D texture descriptors. Finally the CHAP is classified by a Support Vector Machine classifier with histogram intersection kernel that is very effective for high dimensional histogram-based feature representations. Experimental results confirm the effectiveness of the proposed CHAP in terms of computational complexity, storage requirements and classification accuracy when compared to the

  6. Identification of airborne bacterial and fungal species in the clinical microbiology laboratory of a university teaching hospital employing ribosomal DNA (rDNA) PCR and gene sequencing techniques.

    PubMed

    Nagano, Yuriko; Walker, Jim; Loughrey, Anne; Millar, Cherie; Goldsmith, Colin; Rooney, Paul; Elborn, Stuart; Moore, John

    2009-06-01

    Universal or "broad-range" PCR-based ribosomal DNA (rDNA) was performed on a collection of 58 isolates (n = 30 bacteria + 28 fungi), originating from environmental air from several locations within a busy clinical microbiology laboratory, supporting a university teaching hospital. A total of 10 bacterial genera were identified including both Gram-positive and Gram-negative genera. Gram-positive organisms accounted for 27/30 (90%) of total bacterial species, consisting of seven genera and included (in descending order of frequency) Staphylococcus, Micrococcus, Corynebacterium, Paenibacillus, Arthrobacter, Janibacter and Rothia. Gram-negative organisms were less frequently isolated 3/30 (10%) and comprised three genera, including Moraxella, Psychrobacter and Haloanella. Eight fungal genera were identified among the 28 fungal organisms isolated, including (in descending order of frequency) Cladosporium, Penicillium, Aspergillus, Thanatephorus, Absidia, Eurotium, Paraphaeosphaeria and Tritirachium, with Cladosporium accounting for 10/28 (35.7%) of the total fungal isolates. In conclusion, this study identified the presence of 10 bacterial and eight fungal genera in the air within the laboratory sampled. Although this reflected diversity of the microorganisms present, none of these organisms have been described previously as having an inhalational route of laboratory-acquired infection. Therefore, we believe that the species of organisms identified and the concentration levels of these airborne contaminants determined, do not pose a significant health and safety threat for immunocompotent laboratory personnel and visitors. PMID:20183192

  7. Random Amplified Polymorphic DNA Typing of Clinical and Environmental Aeromonas hydrophila Strains from Limpopo Province, South Africa

    PubMed Central

    Ramalivhana, J.N.; Obi, C.L.; Labuschagne, C.; Weldhagen, G.F.

    2010-01-01

    The aim of the present study was to determine the genetic relatedness of strains isolated from diarrhoeal stool and water specimens collected from water-storage containers from different geographical areas in the Limpopo province. In total, 32 Aeromonas strains isolated from stool specimens collected from HIV/AIDS patients suffering from gastroenteritis and their household drinking-water stored in 20-L and 25-L containers were analyzed by random amplified polymorphic DNA PCR (RAPD). The RAPD fingerprints obtained proved reproducible when repeated on three different occasions using whole-cell DNA isolated from the Aeromonas strains. In total, 12 unique RAPD fingerprints were found. The results revealed a tendency of the isolates to cluster according to their origin of isolation (best-cut test 0.80 and bootstrap values >50%). However, a certain degree of similarity was also observed between isolates of water sources and clinical sources which indicated genetic relatedness. There were also genetic similarities between the clinical and the environmental strains of Aeromonas spp. isolated from different geographical areas. This study has demonstrated the genetic relatedness of Aeromonas hydrophila isolates from household drinking-water and clinical sources in South Africa, which may be due to cross-contamination from water to patients or vice-versa. This observation is of public-health significance, particularly in the era of HIV/AIDS. This study points to the importance of monitoring and evaluating infection-control measures for improved hygiene and to prevent cross-contaminations. PMID:20214080

  8. Identification of uterine leiomyoma-specific marker genes based on DNA methylation and their clinical application

    PubMed Central

    Sato, Shun; Maekawa, Ryo; Yamagata, Yoshiaki; Tamura, Isao; Lee, Lifa; Okada, Maki; Jozaki, Kosuke; Asada, Hiromi; Tamura, Hiroshi; Sugino, Norihiro

    2016-01-01

    Differential diagnosis of uterine leiomyomas and leiomyosarcomas is needed to determine whether the uterus can be retained. Therefore, biomarkers for uterine leiomyomas, and reliable and objective diagnostic methods have been desired besides the pathological diagnosis. In the present study, we identified 12 genes specific to uterine leiomyomas based on DNA methylation. Using these marker genes specific to uterine leiomyomas, we established a hierarchical clustering system based on the DNA methylation level of the marker genes, which could completely differentiate between uterine leiomyomas and normal myometrium. Furthermore, our hierarchical clustering system completely discriminated uterine cancers and differentiated between uterine leiomyosarcomas and leiomyomas with more than 70% accuracy. In conclusion, this study identified DNA methylation-based marker genes specific to uterine leiomyomas, and our hierarchical clustering system using these marker genes was useful for differential diagnosis of uterine leiomyomas and leiomyosarcomas. PMID:27498619

  9. Identification of uterine leiomyoma-specific marker genes based on DNA methylation and their clinical application.

    PubMed

    Sato, Shun; Maekawa, Ryo; Yamagata, Yoshiaki; Tamura, Isao; Lee, Lifa; Okada, Maki; Jozaki, Kosuke; Asada, Hiromi; Tamura, Hiroshi; Sugino, Norihiro

    2016-01-01

    Differential diagnosis of uterine leiomyomas and leiomyosarcomas is needed to determine whether the uterus can be retained. Therefore, biomarkers for uterine leiomyomas, and reliable and objective diagnostic methods have been desired besides the pathological diagnosis. In the present study, we identified 12 genes specific to uterine leiomyomas based on DNA methylation. Using these marker genes specific to uterine leiomyomas, we established a hierarchical clustering system based on the DNA methylation level of the marker genes, which could completely differentiate between uterine leiomyomas and normal myometrium. Furthermore, our hierarchical clustering system completely discriminated uterine cancers and differentiated between uterine leiomyosarcomas and leiomyomas with more than 70% accuracy. In conclusion, this study identified DNA methylation-based marker genes specific to uterine leiomyomas, and our hierarchical clustering system using these marker genes was useful for differential diagnosis of uterine leiomyomas and leiomyosarcomas. PMID:27498619

  10. Sites of Retroviral DNA Integration: From Basic Research to Clinical Applications

    PubMed Central

    Serrao, Erik; Engelman, Alan N.

    2016-01-01

    One of the most crucial steps in the life cycle of a retrovirus is the integration of the viral DNA (vDNA) copy of the RNA genome into the genome of an infected host cell. Integration provides for efficient viral gene expression as well as for the segregation of the viral genomes to daughter cells upon cell division. Some integrated viruses are not well expressed, and cells latently infected with HIV-1 can resist the action of potent antiretroviral drugs and remain dormant for decades. Intensive research has been dedicated to understanding the catalytic mechanism of integration, as well as the viral and cellular determinants that influence integration site distribution throughout the host genome. In this review we summarize the evolution of techniques that have been used to recover and map retroviral integration sites, from the early days that first indicated that integration could occur in multiple cellular DNA locations, to current technologies that map upwards of millions of unique integration sites from single in vitro integration reactions or cell culture infections. We further review important insights gained from the use of such mapping techniques, including the monitoring of cell clonal expansion in patients treated with retrovirus-based gene therapy vectors, or AIDS patients on suppressive antiretroviral therapy (ART). These insights span from integrase (IN) enzyme sequence preferences within target DNA (tDNA) at the sites of integration, to the roles of host cellular proteins in mediating global integration distribution, to the potential relationship between genomic location of vDNA integration site and retroviral latency. PMID:26508664

  11. Sites of retroviral DNA integration: From basic research to clinical applications.

    PubMed

    Serrao, Erik; Engelman, Alan N

    2016-01-01

    One of the most crucial steps in the life cycle of a retrovirus is the integration of the viral DNA (vDNA) copy of the RNA genome into the genome of an infected host cell. Integration provides for efficient viral gene expression as well as for the segregation of viral genomes to daughter cells upon cell division. Some integrated viruses are not well expressed, and cells latently infected with human immunodeficiency virus type 1 (HIV-1) can resist the action of potent antiretroviral drugs and remain dormant for decades. Intensive research has been dedicated to understanding the catalytic mechanism of integration, as well as the viral and cellular determinants that influence integration site distribution throughout the host genome. In this review, we summarize the evolution of techniques that have been used to recover and map retroviral integration sites, from the early days that first indicated that integration could occur in multiple cellular DNA locations, to current technologies that map upwards of millions of unique integration sites from single in vitro integration reactions or cell culture infections. We further review important insights gained from the use of such mapping techniques, including the monitoring of cell clonal expansion in patients treated with retrovirus-based gene therapy vectors, or patients with acquired immune deficiency syndrome (AIDS) on suppressive antiretroviral therapy (ART). These insights span from integrase (IN) enzyme sequence preferences within target DNA (tDNA) at the sites of integration, to the roles of host cellular proteins in mediating global integration distribution, to the potential relationship between genomic location of vDNA integration site and retroviral latency. PMID:26508664

  12. CUDA implementation of histogram stretching function for improving X-ray image.

    PubMed

    Lee, Yong H; Kim, Kwan W; Kim, Soon S

    2013-01-01

    This paper presents a method to improve the contrast of digital X-ray image using CUDA program on a GPU. The histogram is commonly used to get the statistical distribution of the contrast in image processing. To increase the visibility of the image in real time, we use the histogram stretching function. It is difficult to implement the function on a GPU because the CUDA program is due to handle the complex process to transfer the source data and the processed results between the memory of GPU and the host system. As a result, we show to operate the histogram stretching function quickly on GPU by the CUDA program. PMID:23920761

  13. Genome-Wide DNA Methylation Analysis Identifies Novel Hypomethylated Non-Pericentromeric Genes with Potential Clinical Implications in ICF Syndrome

    PubMed Central

    Gatto, S.; Gagliardi, M.; Crujeiras, A. B.; Matarazzo, M. R.; Esteller, M.; Sandoval, J.

    2015-01-01

    Introduction and Results Immunodeficiency, centromeric instability and facial anomalies syndrome (ICF) is a rare autosomal recessive disease, characterized by severe hypomethylation in pericentromeric regions of chromosomes (1, 16 and 9), marked immunodeficiency and facial anomalies. The majority of ICF patients present mutations in the DNMT3B gene, affecting the DNA methyltransferase activity of the protein. In the present study, we have used the Infinium 450K DNA methylation array to evaluate the methylation level of 450,000 CpGs in lymphoblastoid cell lines and untrasformed fibroblasts derived from ICF patients and healthy donors. Our results demonstrate that ICF-specific DNMT3B variants A603T/STP807ins and V699G/R54X cause global DNA hypomethylation compared to wild-type protein. We identified 181 novel differentially methylated positions (DMPs) including subtelomeric and intrachromosomic regions, outside the classical ICF-related pericentromeric hypomethylated positions. Interestingly, these sites were mainly located in intergenic regions and inside the CpG islands. Among the identified hypomethylated CpG-island associated genes, we confirmed the overexpression of three selected genes, BOLL, SYCP2 and NCRNA00221, in ICF compared to healthy controls, which are supposed to be expressed in germ line and silenced in somatic tissues. Conclusions In conclusion, this study contributes in clarifying the direct relationship between DNA methylation defect and gene expression impairment in ICF syndrome, identifying novel direct target genes of DNMT3B. A high percentage of the DMPs are located in the subtelomeric regions, indicating a specific role of DNMT3B in methylating these chromosomal sites. Therefore, we provide further evidence that hypomethylation in specific non-pericentromeric regions of chromosomes might be involved in the molecular pathogenesis of ICF syndrome. The detection of DNA hypomethylation at BOLL, SYCP2 and NCRNA00221 may pave the way for the

  14. Macrolide Resistance in Treponema pallidum Correlates With 23S rDNA Mutations in Recently Isolated Clinical Strains

    PubMed Central

    Molini, Barbara J.; Tantalo, Lauren C.; Sahi, Sharon K.; Rodriguez, Veronica I.; Brandt, Stephanie L.; Fernandez, Mark C.; Godornes, Charmie B.; Marra, Christina M.; Lukehart, Sheila A.

    2016-01-01

    Background High rates of 23S rDNA mutations implicated in macrolide resistance have been identified in Treponema pallidum samples from syphilis patients in many countries. Nonetheless, some clinicians have been reluctant to abandon azithromycin as a treatment for syphilis, citing the lack of a causal association between these mutations and clinical evidence of drug resistance. Although azithromycin resistance has been demonstrated in vivo for the historical Street 14 strain, no recent T. pallidum isolates have been tested. We used the well-established rabbit model of syphilis to determine the in vivo efficacy of azithromycin against 23S rDNA mutant strains collected in 2004 to 2005 from patients with syphilis in Seattle, Wash. Methods Groups of 9 rabbits were each infected with a strain containing 23S rDNA mutation A2058G (strains UW074B, UW189B, UW391B) or A2059G (strains UW228B, UW254B, and UW330B), or with 1 wild type strain (Chicago, Bal 3, and Mexico A). After documentation of infection, 3 animals per strain were treated with azithromycin, 3 were treated with benzathine penicillin G, and 3 served as untreated control groups. Treatment efficacy was documented by darkfield microscopic evidence of T. pallidum, serological response, and rabbit infectivity test. Results Azithromycin uniformly failed to cure rabbits infected with strains harboring either 23S rDNA mutation, although benzathine penicillin G was effective. Infections caused by wild type strains were successfully treated by either azithromycin or benzathine penicillin G. Conclusions A macrolide resistant phenotype was demonstrated for all strains harboring a 23S rDNA mutation, demonstrating that either A2058G or A2059G mutation confers in vivo drug resistance. PMID:27513385

  15. Surface IgM expression and function are associated with clinical behavior, genetic abnormalities, and DNA methylation in CLL.

    PubMed

    D'Avola, Annalisa; Drennan, Samantha; Tracy, Ian; Henderson, Isla; Chiecchio, Laura; Larrayoz, Marta; Rose-Zerilli, Matthew; Strefford, Jonathan; Plass, Christoph; Johnson, Peter W; Steele, Andrew J; Packham, Graham; Stevenson, Freda K; Oakes, Christopher C; Forconi, Francesco

    2016-08-11

    Chronic lymphocytic leukemia (CLL) with unmutated (U-CLL) or mutated (M-CLL) immunoglobulin gene heavy-chain variable region (IGHV) displays different states of anergy, indicated by reduced surface immunoglobulin M (sIgM) levels and signaling, consequent to chronic (super)antigen exposure. The subsets also differ in the incidence of high-risk genetic aberrations and in DNA methylation profile, preserved from the maturational status of the original cell. We focused on sIgM expression and function, measured as intracellular Ca(2+) mobilization following stimulation, and probed correlations with clinical outcome. The relationship with genetic features and maturation status defined by DNA methylation of an 18-gene panel signature was then investigated. sIgM levels/signaling were higher and less variable in U-CLL than in M-CLL and correlated with disease progression between and within U-CLL and M-CLL. In U-CLL, increased levels/signaling associated with +12, del(17p) or NOTCH1 mutations. In M-CLL, there were fewer genetic lesions, although the methylation maturation status, generally higher than in U-CLL, varied and was increased in cases with lower sIgM levels/signaling. These features revealed heterogeneity in M-CLL and U-CLL with clear clinical correlations. Multivariate analyses with phenotype, genetic lesions, or DNA methylation maturation status identified high sIgM levels as a new potential independent factor for disease progression. Multiple influences on sIgM include the cell of origin, the clonal history of antigen encounter in vivo, and genetic damage. This simple marker compiles these different factors into an indicator worthy of further investigations for prediction of clinical behavior, particularly within the heterogeneous M-CLL subset. PMID:27301861

  16. Evidence from clinical and animal model studies of the long-term and transgenerational impact of stress on DNA methylation

    PubMed Central

    Blaze, Jennifer; Roth, Tania L.

    2015-01-01

    While it is well-known that stress during development and adulthood can confer long-term neurobiological and behavioral consequences, investigators have only recently begun to assess epigenetic modifications associated with these consequences. In this review, we highlight clinical research and work with animal models that provide evidence of the impact of stressful experiences either during the perinatal period or adulthood on DNA methylation and behavior. Additionally, we explore the more controversial concept of transgenerational inheritance, including that associated with preconception stress experienced by the mother or father. Finally, we discuss challenges associated with the idea of transgenerational epigenetics and for the field of epigenetics in general. PMID:25917771

  17. Histogram analysis of ADC in brain tumor patients

    NASA Astrophysics Data System (ADS)

    Banerjee, Debrup; Wang, Jihong; Li, Jiang

    2011-03-01

    At various stage of progression, most brain tumors are not homogenous. In this presentation, we retrospectively studied the distribution of ADC values inside tumor volume during the course of tumor treatment and progression for a selective group of patients who underwent an anti-VEGF trial. Complete MRI studies were obtained for this selected group of patients including pre- and multiple follow-up, post-treatment imaging studies. In each MRI imaging study, multiple scan series were obtained as a standard protocol which includes T1, T2, T1-post contrast, FLAIR and DTI derived images (ADC, FA etc.) for each visit. All scan series (T1, T2, FLAIR, post-contrast T1) were registered to the corresponding DTI scan at patient's first visit. Conventionally, hyper-intensity regions on T1-post contrast images are believed to represent the core tumor region while regions highlighted by FLAIR may overestimate tumor size. Thus we annotated tumor regions on the T1-post contrast scans and ADC intensity values for pixels were extracted inside tumor regions as defined on T1-post scans. We fit a mixture Gaussian (MG) model for the extracted pixels using the Expectation-Maximization (EM) algorithm, which produced a set of parameters (mean, various and mixture coefficients) for the MG model. This procedure was performed for each visits resulting in a series of GM parameters. We studied the parameters fitted for ADC and see if they can be used as indicators for tumor progression. Additionally, we studied the ADC characteristics in the peri-tumoral region as identified by hyper-intensity on FLAIR scans. The results show that ADC histogram analysis of the tumor region supports the two compartment model that suggests the low ADC value subregion corresponding to densely packed cancer cell while the higher ADC value region corresponding to a mixture of viable and necrotic cells with superimposed edema. Careful studies of the composition and relative volume of the two compartments in tumor

  18. Efficient Human Action and Gait Analysis Using Multiresolution Motion Energy Histogram

    NASA Astrophysics Data System (ADS)

    Yu, Chih-Chang; Cheng, Hsu-Yung; Cheng, Chien-Hung; Fan, Kuo-Chin

    2010-12-01

    Average Motion Energy (AME) image is a good way to describe human motions. However, it has to face the computation efficiency problem with the increasing number of database templates. In this paper, we propose a histogram-based approach to improve the computation efficiency. We convert the human action/gait recognition problem to a histogram matching problem. In order to speed up the recognition process, we adopt a multiresolution structure on the Motion Energy Histogram (MEH). To utilize the multiresolution structure more efficiently, we propose an automated uneven partitioning method which is achieved by utilizing the quadtree decomposition results of MEH. In that case, the computation time is only relevant to the number of partitioned histogram bins, which is much less than the AME method. Two applications, action recognition and gait classification, are conducted in the experiments to demonstrate the feasibility and validity of the proposed approach.

  19. Matching of flow-cytometry histograms using information theory in feature space.

    PubMed Central

    Zeng, Qing; Wand, Matthew; Young, Alan J.; Rawn, James; Milford, Edgar L.; Mentzer, Steven J.; Greenes, Robert A.

    2002-01-01

    Flow cytometry is a widely available technique for analyzing cell-surface protein expression. Data obtained from flow cytometry is frequently used to produce fluorescence intensity histograms. Comparison of histograms can be useful in the identification of unknown molecules and in the analysis of protein expression. In this study, we examined the combination of a new smoothing technique called SiZer with information theory to measure the difference between cytometry histograms. SiZer provides cross-bandwidth smoothing and allowed analysis in feature space. The new methods were tested on a panel of monoclonal antibodies raised against proteins expressed on peripheral blood lymphocytes and compared with previous methods. The findings suggest that comparing information content of histograms in feature space is effective and efficient for identifying antibodies with similar cell-surface binding patterns. PMID:12463961

  20. Application of Histogram Analysis in Radiation Therapy (HART) in Intensity Modulation Radiation Therapy (IMRT) Treatments

    NASA Astrophysics Data System (ADS)

    Pyakuryal, Anil

    2009-03-01

    A carcinoma is a malignant cancer that emerges from epithelial cells in structures through out the body.It invades the critical organs, could metastasize or spread to lymph nodes.IMRT is an advanced mode of radiation therapy treatment for cancer. It delivers more conformal doses to malignant tumors sparing the critical organs by modulating the intensity of radiation beam.An automated software, HART (S. Jang et al.,2008,Med Phys 35,p.2812) was used for efficient analysis of dose volume histograms (DVH) for multiple targets and critical organs in four IMRT treatment plans for each patient. IMRT data for ten head and neck cancer patients were exported as AAPM/RTOG format files from a commercial treatment planning system at Northwestern Memorial Hospital (NMH).HART extracted DVH statistics were used to evaluate plan indices and to analyze dose tolerance of critical structures at prescription dose (PD) for each patient. Mean plan indices (n=10) were found to be in good agreement with published results for Linac based plans. The least irradiated volume at tolerance dose (TD50) was observed for brainstem and the highest volume for larynx in SIB treatment techniques. Thus HART, an open source platform, has extensive clinical implications in IMRT treatments.

  1. Quality control of dose volume histogram computation characteristics of 3D treatment planning systems

    NASA Astrophysics Data System (ADS)

    Panitsa, E.; Rosenwald, J. C.; Kappas, C.

    1998-10-01

    Detailed quality control (QC) protocols are a necessity for modern radiotherapy departments. The established QC protocols for treatment planning systems (TPS) do not include recommendations on the advanced features of three-dimensional (3D) treatment planning, like the dose volume histograms (DVH). In this study, a test protocol for DVH characteristics was developed. The protocol assesses the consistency of the DVH computation to the dose distribution calculated by the same TPS by comparing DVH parameters with values obtained by the isodose distributions. The computation parameters (such as the dimension of the computation grid) that are applied to the TPS during the tests are not fixed but set by the user as if the test represents a typical clinical case. Six commercial TPS were examined with this protocol within the frame of the EC project Dynarad (Biomed I). The results of the intercomparison prove the consistency of the DVH results to the isodose values for most of the examined TPS. However, special attention should be paid when working with cases of adverse conditions such as high dose gradient regions. In these cases, higher errors are derived, especially when an insufficient number of dose calculation points are used for the DVH computation.

  2. Comparison of Antifungal Activities and 16S Ribosomal DNA Sequences of Clinical and Environmental Isolates of Stenotrophomonas maltophilia

    PubMed Central

    Minkwitz, Arite; Berg, Gabriele

    2001-01-01

    In recent years, the gram-negative bacterium Stenotrophomonas maltophilia has become increasingly important in biotechnology and as a nosocomial pathogen, giving rise to a need for new information about its taxonomy and epidemiology. To determine intraspecies diversity and whether strains can be distinguished based on the sources of their isolation, 50 S. maltophilia isolates from clinical and environmental sources, including strains of biotechnological interest, were investigated. The isolates were characterized by in vitro antagonism against pathogenic fungi and the production of antifungal metabolites and enzymes. Phenotypically the strains showed variability that did not correlate significantly with their sources of isolation. Clinical strains displayed remarkable activity against the human pathogenic fungus Candida albicans. Antifungal activity against plant pathogens was more common and generally more severe from the environmental isolates, although not exclusive to them. All isolates, clinical and environmental, produced a range of antifungal metabolites including antibiotics, siderophores, and the enzymes proteases and chitinases. From 16S ribosomal DNA sequencing analysis, the isolates could be separated into three clusters, two of which consisted of isolates originating from the environment, especially rhizosphere isolates, and one of which consisted of clinical and aquatic strains. In contrast to the results of other recent investigations, these strains could be grouped based on their sources of isolation, with the exception of three rhizosphere isolates. Because there was evidence of nucleotide signature positions within the sequences that are suitable for distinguishing among the clusters, the clusters could be defined as different genomovars of S. maltophilia. Key sequences on the 16S ribosomal DNA could be used to develop a diagnostic method that differentiates these genomovars. PMID:11136762

  3. Genome-Wide DNA Copy Number Analysis of Acute Lymphoblastic Leukemia Identifies New Genetic Markers Associated with Clinical Outcome

    PubMed Central

    Forero-Castro, Maribel; Robledo, Cristina; Benito, Rocío; Abáigar, María; África Martín, Ana; Arefi, Maryam; Fuster, José Luis; de las Heras, Natalia; Rodríguez, Juan N.; Quintero, Jonathan; Riesco, Susana; Hermosín, Lourdes; de la Fuente, Ignacio; Recio, Isabel; Ribera, Jordi; Labrador, Jorge; Alonso, José M.; Olivier, Carmen; Sierra, Magdalena; Megido, Marta; Corchete-Sánchez, Luis A.; Ciudad Pizarro, Juana; García, Juan Luis; Ribera, José M.; Hernández-Rivas, Jesús M.

    2016-01-01

    Identifying additional genetic alterations associated with poor prognosis in acute lymphoblastic leukemia (ALL) is still a challenge. Aims: To characterize the presence of additional DNA copy number alterations (CNAs) in children and adults with ALL by whole-genome oligonucleotide array (aCGH) analysis, and to identify their associations with clinical features and outcome. Array-CGH was carried out in 265 newly diagnosed ALLs (142 children and 123 adults). The NimbleGen CGH 12x135K array (Roche) was used to analyze genetic gains and losses. CNAs were analyzed with GISTIC and aCGHweb software. Clinical and biological variables were analyzed. Three of the patients showed chromothripsis (cth6, cth14q and cth15q). CNAs were associated with age, phenotype, genetic subtype and overall survival (OS). In the whole cohort of children, the losses on 14q32.33 (p = 0.019) and 15q13.2 (p = 0.04) were related to shorter OS. In the group of children without good- or poor-risk cytogenetics, the gain on 1p36.11 was a prognostic marker independently associated with shorter OS. In adults, the gains on 19q13.2 (p = 0.001) and Xp21.1 (p = 0.029), and the loss of 17p (p = 0.014) were independent markers of poor prognosis with respect to OS. In summary, CNAs are frequent in ALL and are associated with clinical parameters and survival. Genome-wide DNA copy number analysis allows the identification of genetic markers that predict clinical outcome, suggesting that detection of these genetic lesions will be useful in the management of patients newly diagnosed with ALL. PMID:26872047

  4. Detection and quantification of parapoxvirus DNA by use of a quantitative real-time polymerase chain reaction assay in calves without clinical signs of parapoxvirus infection.

    PubMed

    Yaegashi, Gakuji; Fukunari, Kazuhiro; Oyama, Takayuki; Murakami, Ryu-Koh; Inoshima, Yasuo

    2016-04-01

    OBJECTIVE To investigate the presence of parapoxvirus (PPV) in cattle without clinical signs of infection and in farm environments of PPV-infected cattle. ANIMALS 28 calves without clinical signs of PPV infection on 2 farms and 11 clinically affected calves on 6 farms. PROCEDURES 164 oral swab samples were collected at regular intervals from 28 calves without clinical signs of PPV infection, and 11 swab samples were collected from 11 clinically affected calves. Viral DNA load was quantified by use of a PPV-specific quantitative real-time PCR (qRT-PCR) assay. RESULTS Of 28 calves without clinical signs of PPV infection, 12 had positive results for PPV DNA by use of the qRT-PCR assay. Viral DNA was detected continuously over a period of 2 to 5 months from 9 of these 12 calves, particularly from calves with dermatomycosis or respiratory tract disease. The PPV DNA loads in 32 oral swab samples from these 12 calves were significantly lower (median, 3.2 copies/mg) than those in samples collected from the 11 clinically affected calves (median, 3.2 × 10(4) copies/mg). Moreover, PPV DNA was detected in the residual feed and drinking water on both farms that housed the calves without clinical signs of PPV infection. CONCLUSIONS AND CLINICAL RELEVANCE PPV in cattle without clinical signs of infection and in the environments of these cattle may represent sources of PPV transmission to susceptible cattle. IMPACT FOR HUMAN MEDICINE Humans should wear gloves to prevent zoonotic disease transmission when handling cattle with or without clinical signs of PPV infection. PMID:27027837

  5. Childhood mitochondrial encephalomyopathies: clinical course, diagnosis, neuroimaging findings, mtDNA mutations and outcome in six children

    PubMed Central

    2013-01-01

    Mitochondrial dysfunction manifests in many forms during childhood. There is no effective therapy for the condition; hence symptomatic therapy is the only option. The effect of symptomatic therapy are not well known. We present clinical course, diagnosis and effect of current treatments for six children suffering from mitochondrial encephalomyopathy identified by clinical demonstrations, brain MRI findings and DNA mutations. Two were male and four were female. Their age ranged between 2 and 17 years. Skeletal muscle biopsies were obtained in three and one showed misshaped and enlarged mitochondria under electron microscope. mtDNA mutation frequency was >30%. Five children were diagnosed with MELAS (mitochondrial encephalopathy, lactic acidosis, and strokelike episodes) and one with Leigh’s syndrome (LS). All were given cocktail and symptomatic treatments. One of the five MELAS children died from severe complications. The other four MELAS children remain alive; four showed improvement, and one remained unresponsive. Of the four who showed improvement, two do not have any abnormal signs and the other two have some degree of motor developmental delay and myotrophy. The LS child is doing well except for ataxia. Until better therapy such as mitochondrial gene therapy is available, cocktail and symptomatic treatments could at least stabilize these children. PMID:24069936

  6. A multi-parametric workflow for the prioritization of mitochondrial DNA variants of clinical interest.

    PubMed

    Santorsola, Mariangela; Calabrese, Claudia; Girolimetti, Giulia; Diroma, Maria Angela; Gasparre, Giuseppe; Attimonelli, Marcella

    2016-01-01

    Assigning a pathogenic role to mitochondrial DNA (mtDNA) variants and unveiling the potential involvement of the mitochondrial genome in diseases are challenging tasks in human medicine. Assuming that rare variants are more likely to be damaging, we designed a phylogeny-based prioritization workflow to obtain a reliable pool of candidate variants for further investigations. The prioritization workflow relies on an exhaustive functional annotation through the mtDNA extraction pipeline MToolBox and includes Macro Haplogroup Consensus Sequences to filter out fixed evolutionary variants and report rare or private variants, the nucleotide variability as reported in HmtDB and the disease score based on several predictors of pathogenicity for non-synonymous variants. Cutoffs for both the disease score as well as for the nucleotide variability index were established with the aim to discriminate sequence variants contributing to defective phenotypes. The workflow was validated on mitochondrial sequences from Leber's Hereditary Optic Neuropathy affected individuals, successfully identifying 23 variants including the majority of the known causative ones. The application of the prioritization workflow to cancer datasets allowed to trim down the number of candidate for subsequent functional analyses, unveiling among these a high percentage of somatic variants. Prioritization criteria were implemented in both standalone ( http://sourceforge.net/projects/mtoolbox/ ) and web version ( https://mseqdr.org/mtoolbox.php ) of MToolBox. PMID:26621530

  7. De-Striping for Tdiccd Remote Sensing Image Based on Statistical Features of Histogram

    NASA Astrophysics Data System (ADS)

    Gao, Hui-ting; Liu, Wei; He, Hong-yan; Zhang, Bing-xian; Jiang, Cheng

    2016-06-01

    Aim to striping noise brought by non-uniform response of remote sensing TDI CCD, a novel de-striping method based on statistical features of image histogram is put forward. By analysing the distribution of histograms,the centroid of histogram is selected to be an eigenvalue representing uniformity of ground objects,histogrammic centroid of whole image and each pixels are calculated first,the differences between them are regard as rough correction coefficients, then in order to avoid the sensitivity caused by single parameter and considering the strong continuity and pertinence of ground objects between two adjacent pixels,correlation coefficient of the histograms is introduces to reflect the similarities between them,fine correction coefficient is obtained by searching around the rough correction coefficient,additionally,in view of the influence of bright cloud on histogram,an automatic cloud detection based on multi-feature including grey level,texture,fractal dimension and edge is used to pre-process image.Two 0-level panchromatic images of SJ-9A satellite with obvious strip noise are processed by proposed method to evaluate the performance, results show that the visual quality of images are improved because the strip noise is entirely removed,we quantitatively analyse the result by calculating the non-uniformity ,which has reached about 1% and is better than histogram matching method.

  8. Region of Interest Detection Based on Histogram Segmentation for Satellite Image

    NASA Astrophysics Data System (ADS)

    Kiadtikornthaweeyot, Warinthorn; Tatnall, Adrian R. L.

    2016-06-01

    High resolution satellite imaging is considered as the outstanding applicant to extract the Earth's surface information. Extraction of a feature of an image is very difficult due to having to find the appropriate image segmentation techniques and combine different methods to detect the Region of Interest (ROI) most effectively. This paper proposes techniques to classify objects in the satellite image by using image processing methods on high-resolution satellite images. The systems to identify the ROI focus on forests, urban and agriculture areas. The proposed system is based on histograms of the image to classify objects using thresholding. The thresholding is performed by considering the behaviour of the histogram mapping to a particular region in the satellite image. The proposed model is based on histogram segmentation and morphology techniques. There are five main steps supporting each other; Histogram classification, Histogram segmentation, Morphological dilation, Morphological fill image area and holes and ROI management. The methods to detect the ROI of the satellite images based on histogram classification have been studied, implemented and tested. The algorithm is be able to detect the area of forests, urban and agriculture separately. The image segmentation methods can detect the ROI and reduce the size of the original image by discarding the unnecessary parts.

  9. Clinical utility of a DNA probe to 17p11.2 in screening of patients with a peripheral neuropathy

    SciTech Connect

    Blancato, J.; Precht, K.; Meck, J.

    1994-09-01

    We assessed the usefulness of in situ hybridization with a DNA probe to the area of chromosome 17 at p11.2 as a diagnostic tool for screening for Charcot Marte Tooth 1A (CMT 1A). In situ hybridization with a probe to 17p11.2 was performed on fixed lymphocytes from the following groups of individuals: (1) normal controls; (2) patients evoking a strong clinical suspicion of CMT 1A; and (3) 3 families with an apparent autosomal dominant peripheral neuropathy of unknown diagnoses. Group 2 patients had evidence of demyelination as defined by nerve conduction of less that 50% of the normal mean or terminal latency greater than 50% of the normal mean in conduction studies. Analysis of interphase cells hybridized with a cosmid DNA probe to 17p11.2 requires inclusion of a normal control with each trial and masked observer. Due to the size of the target DNA and the nature of the centromeric heterochromatin, the scoring of this probe is more subjective than centromere probes. For example, if the two 17 chromosomes are decondensed as in interphase, two tandem signals may be visualized as one. Results from duplication positive patients demonstrate a large proportion of cells with two closely aligned, but separate, signals with an additional single signal. Normal results demonstrate a majority of cells with two separate signals representing both normal homologues. None of the 3 families with questionable diagnosis revealed a duplication at the region, reinforcing our belief that a clinical diagnosis is the most discriminating tool available for diagnosis of CMT 1A. We concur with Boylan that molecular analysis for CMT 1A is useful for establishing a diagnosis of CMT 1A, but is not a primary differential diagnostic test. The yield in screening patients without physiologic evidence of demyelination is likely to be low. We further find that the use of in situ hybridization is a simple method of performing the duplication analysis.

  10. Sequencing and comparative genomic analysis of 1227 Felis catus cDNA sequences enriched for developmental, clinical and nutritional phenotypes

    PubMed Central

    2012-01-01

    Background The feline genome is valuable to the veterinary and model organism genomics communities because the cat is an obligate carnivore and a model for endangered felids. The initial public release of the Felis catus genome assembly provided a framework for investigating the genomic basis of feline biology. However, the entire set of protein coding genes has not been elucidated. Results We identified and characterized 1227 protein coding feline sequences, of which 913 map to public sequences and 314 are novel. These sequences have been deposited into NCBI's genbank database and complement public genomic resources by providing additional protein coding sequences that fill in some of the gaps in the feline genome assembly. Through functional and comparative genomic analyses, we gained an understanding of the role of these sequences in feline development, nutrition and health. Specifically, we identified 104 orthologs of human genes associated with Mendelian disorders. We detected negative selection within sequences with gene ontology annotations associated with intracellular trafficking, cytoskeleton and muscle functions. We detected relatively less negative selection on protein sequences encoding extracellular networks, apoptotic pathways and mitochondrial gene ontology annotations. Additionally, we characterized feline cDNA sequences that have mouse orthologs associated with clinical, nutritional and developmental phenotypes. Together, this analysis provides an overview of the value of our cDNA sequences and enhances our understanding of how the feline genome is similar to, and different from other mammalian genomes. Conclusions The cDNA sequences reported here expand existing feline genomic resources by providing high-quality sequences annotated with comparative genomic information providing functional, clinical, nutritional and orthologous gene information. PMID:22257742

  11. Protective Effect of Folic Acid on Oxidative DNA Damage: A Randomized, Double-Blind, and Placebo Controlled Clinical Trial.

    PubMed

    Guo, Xiaojuan; Cui, Huan; Zhang, Haiyang; Guan, Xiaoju; Zhang, Zheng; Jia, Chaonan; Wu, Jia; Yang, Hui; Qiu, Wenting; Zhang, Chuanwu; Yang, Zuopeng; Chen, Zhu; Mao, Guangyun

    2015-11-01

    Although previous reports have linked DNA damage with both transmissions across generations as well as our own survival, it is unknown how to reverse the lesion. Based on the data from a Randomized, Double-blind, Placebo Controlled Clinical Trial, this study aimed to assess the efficacy of folic acid supplementation (FAS) on DNA oxidative damage reversal.In this randomized clinical trial (RCT), a total of 450 participants were enrolled and randomly assigned to 3 groups to receive folic acid (FA) 0.4 mg/day (low-FA), 0.8 mg/day (high-FA), or placebo (control) for 8 weeks. The urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and creatinine (Cr) concentration at pre- and post-FAS were measured with modified enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography (HPLC), respectively. A multivariate general linear model was applied to assess the individual effects of FAS and the joint effects between FAS and hypercholesterolemia on oxidative DNA damage improvement. This clinical trial was registered with ClinicalTrials.gov, number NCT02235948.Of the 438 subjects that received FA fortification or placebo, the median (first quartile, third quartile) of urinary 8-OHdG/Cr for placebo, low-FA, and high-FA groups were 58.19 (43.90, 82.26), 53.51 (38.97, 72.74), 54.73 (39.58, 76.63) ng/mg at baseline and 57.77 (44.35, 81.33), 51.73 (38.20, 71.30), and 50.65 (37.64, 76.17) ng/mg at the 56th day, respectively. A significant decrease of urinary 8-OHdG was observed after 56 days FA fortification (P < 0.001). Compared with the placebo, after adjusting for some potential confounding factors, including the baseline urinary 8-OHdG/Cr, the urinary 8-OHdG/Cr concentration significantly decreased after 56 days FAS [β (95% confidence interval) = -0.88 (-1.62, -0.14) and P = 0.020 for low-FA; and β (95% confidence interval) = -2.68 (-3.42, -1.94) and P < 0.001 for high-FA] in a dose-response fashion (Ptrend < 0.001). Test of

  12. Clinical Development of a Cytomegalovirus DNA Vaccine: From Product Concept to Pivotal Phase 3 Trial

    PubMed Central

    Smith, Larry R.; Wloch, Mary K.; Chaplin, Jennifer A.; Gerber, Michele; Rolland, Alain P.

    2013-01-01

    2013 marks a milestone year for plasmid DNA vaccine development as a first-in-class cytomegalovirus (CMV) DNA vaccine enters pivotal phase 3 testing. This vaccine consists of two plasmids expressing CMV antigens glycoprotein B (gB) and phosphoprotein 65 (pp65) formulated with a CRL1005 poloxamer and benzalkonium chloride (BAK) delivery system designed to enhance plasmid expression. The vaccine’s planned initial indication under investigation is for prevention of CMV reactivation in CMV-seropositive (CMV+) recipients of an allogeneic hematopoietic stem cell transplant (HCT). A randomized, double-blind placebo-controlled phase 2 proof-of-concept study provided initial evidence of the safety of this product in CMV+ HCT recipients who underwent immune ablation conditioning regimens. This study revealed a significant reduction in viral load endpoints and increased frequencies of pp65-specific interferon-γ-producing T cells in vaccine recipients compared to placebo recipients. The results of this endpoint-defining trial provided the basis for defining the primary and secondary endpoints of a global phase 3 trial in HCT recipients. A case study is presented here describing the development history of this vaccine from product concept to initiation of the phase 3 trial. PMID:26344340

  13. Characterization of Scedosporium prolificans clinical isolates by randomly amplified polymorphic DNA analysis.

    PubMed Central

    San Millán, R; Quindós, G; Garaizar, J; Salesa, R; Guarro, J; Pontón, J

    1997-01-01

    Fingerprinting by randomly amplified polymorphic DNA (RAPD) analysis was used to differentiate Scedosporium prolificans isolates. A total of 59 arbitrary primers were screened with six unrelated S. prolificans isolates, and a panel of 12 primers was selected. The 12 primers were then used to detect DNA polymorphisms among 17 S. prolificans isolates from 11 patients with systemic S. prolificans infections diagnosed in three hospitals located in geographically different areas of Spain. Eight patients were diagnosed with S. prolificans infection in a single institution over a 6-year period, and two other patients were diagnosed with S. prolificans infection in a different hospital over a 1-year period. No single primer allowed for the discrimination of all the isolates from different patients, but this was possible by combining the RAPD patterns from three primers (UBC 701, AB1.08, and AB1.11 or UBC 701, AB1.08, and UBC 707). However, multiple isolates from the same patient were identical. In this study, we also compared a visual method and a computerized method for the analysis of the RAPD patterns. Both methods were satisfactory and gave few discordances, but given the advantages and disadvantages of each method, both systems should be used together. RAPD analysis provided a fast and economical means of typing S. prolificans isolates, with a high level of discrimination among unrelated isolates. Typing by RAPD analysis confirmed that the S. prolificans infections were epidemiologically unrelated. PMID:9276400

  14. Coupling of Geant4-DNA physics models into the GATE Monte Carlo platform: Evaluation of radiation-induced damage for clinical and preclinical radiation therapy beams

    NASA Astrophysics Data System (ADS)

    Pham, Q. T.; Anne, A.; Bony, M.; Delage, E.; Donnarieix, D.; Dufaure, A.; Gautier, M.; Lee, S. B.; Micheau, P.; Montarou, G.; Perrot, Y.; Shin, J. I.; Incerti, S.; Maigne, L.

    2015-06-01

    The GATE Monte Carlo simulation platform based on the Geant4 toolkit is in constant improvement for dosimetric calculations. In this paper, we present the integration of Geant4-DNA processes into the GATE 7.0 platform in the objective to perform multi-scale simulations (from macroscopic to nanometer scale). We simulated three types of clinical and preclinical beams: a 6 MeV electron clinical beam, a X-ray irradiator beam and a clinical proton beam for which we validated depth dose distributions against measurements in water. Frequencies of energy depositions and DNA damage were evaluated using a specific algorithm in charge of allocating energy depositions to atoms constituting DNA molecules represented by their PDB (Protein Data Bank) description.

  15. Mate-Pair Sequencing as a Powerful Clinical Tool for the Characterization of Cancers with a DNA Viral Etiology

    PubMed Central

    Gao, Ge; Smith, David I.

    2015-01-01

    DNA viruses are known to be associated with a variety of different cancers. Human papillomaviruses (HPV) are a family of viruses and several of its sub-types are classified as high-risk HPVs as they are found to be associated with the development of a number of different cancers. Almost all cervical cancers appear to be driven by HPV infection and HPV is also found in most cancers of the anus and at least half the cancers of the vulva, penis and vagina, and increasingly found in one sub-type of head and neck cancers namely oropharyngeal squamous cell carcinoma. Our understanding of HPVs role in cancer development comes from extensive studies done on cervical cancer and it has just been assumed that HPV plays an identical role in the development of all other cancers arising in the presence of HPV sequences, although this has not been proven. Most invasive cervical cancers have the HPV genome integrated into one or more sites within the human genome. One powerful tool to examine all the sites of HPV integration in a cancer but that also provides a comprehensive view of genomic alterations in that cancer is the use of next generation sequencing of mate-pair libraries produced from the DNA isolated. We will describe how this powerful technology can provide important information about the genomic organization within an individual cancer genome, and how this has demonstrated that HPVs role in oropharyngeal squamous cell carcinoma is distinct from that in cervical cancer. We will also describe why the sequencing of mate-pair libraries could be a powerful clinical tool for the management of patients with a DNA viral etiology and how this could quickly transform the care of these patients. PMID:26262638

  16. Clinical heterogeneity within xeroderma pigmentosum associated with mutations in the DNA repair and transcription gene ERCC3

    SciTech Connect

    Vermeulen, W.; Kleijer, W.J.; Bootsma, D.; Hoeijmakers, J.H.J.; Weeda, G. ); Scott, R.J.; Rodgers, S.; Mueller, H.J. ); Cole, J.; Arlett, C.F. )

    1994-02-01

    The human DNA excision repair gene ERCC3 specifically corrects the nucleotide excision repair (NER) defect of xeroderma pigmentosum (XP) complementation group B. In addition to its function in NER, the ERCC3 DNA helicase was recently identified as one of the components of the human BTF2/TFIIH transcription factor complex, which is required for initiation of transcription of class II genes. To date, a single patient (XP11BE) has been assigned to this XP group B (XP-B), with the remarkable conjunction of two autosomal recessive DNA repair deficiency disorders: XP and Cockayne syndrome (CS). The intriguing involvement of the ERCC3 protein in the vital process of transcription may provide an explanation for the rarity, severity, and wide spectrum of clinical features in this complementation group. Here the authors report the identification of two new XP-B patients: XPCS1BA and XPCS2BA (siblings), by microneedle injection of the cloned ERCC3 repair gene as well as by cell hybridization. Molecular analysis of the ERCC3 gene in both patients revealed a single base substitution causing a missense mutation in a region that is completely conserved in yeast, Drosophila, mouse, and human ERCC3. As in patient XP11BE, the expression of only one allele (paternal) is detected. The mutation causes a virtually complete inactivation of the NER function of the protein. Despite this severe NER defect, both patients display a late onset of neurologic impairment, mild cutaneous symptoms, and a striking absence of skin tumors even at an age of >40 years. Analysis of the frequency of hprt[sup [minus

  17. Mate-Pair Sequencing as a Powerful Clinical Tool for the Characterization of Cancers with a DNA Viral Etiology.

    PubMed

    Gao, Ge; Smith, David I

    2015-08-01

    DNA viruses are known to be associated with a variety of different cancers. Human papillomaviruses (HPV) are a family of viruses and several of its sub-types are classified as high-risk HPVs as they are found to be associated with the development of a number of different cancers. Almost all cervical cancers appear to be driven by HPV infection and HPV is also found in most cancers of the anus and at least half the cancers of the vulva, penis and vagina, and increasingly found in one sub-type of head and neck cancers namely oropharyngeal squamous cell carcinoma. Our understanding of HPVs role in cancer development comes from extensive studies done on cervical cancer and it has just been assumed that HPV plays an identical role in the development of all other cancers arising in the presence of HPV sequences, although this has not been proven. Most invasive cervical cancers have the HPV genome integrated into one or more sites within the human genome. One powerful tool to examine all the sites of HPV integration in a cancer but that also provides a comprehensive view of genomic alterations in that cancer is the use of next generation sequencing of mate-pair libraries produced from the DNA isolated. We will describe how this powerful technology can provide important information about the genomic organization within an individual cancer genome, and how this has demonstrated that HPVs role in oropharyngeal squamous cell carcinoma is distinct from that in cervical cancer. We will also describe why the sequencing of mate-pair libraries could be a powerful clinical tool for the management of patients with a DNA viral etiology and how this could quickly transform the care of these patients. PMID:26262638

  18. Plasma EGFR T790M ctDNA status is associated with clinical outcome in advanced NSCLC patients with acquired EGFR-TKI resistance.

    PubMed

    Zheng, D; Ye, X; Zhang, M Z; Sun, Y; Wang, J Y; Ni, J; Zhang, H P; Zhang, L; Luo, J; Zhang, J; Tang, L; Su, B; Chen, G; Zhu, G; Gu, Y; Xu, J F

    2016-01-01

    EGFR T790M mutation occurs in half of non-small cell lung cancer (NSCLC) patients with acquired EGFR-TKI (TKI) resistance, based on tumor re-biopsies using an invasive clinical procedure. Here, we dynamically monitored T790M mutation in circulating tumor DNA (ctDNA) using serial plasma samples from NSCLC patients receiving TKI through Droplet Digital PCR (ddPCR) method and the associations between overall survival (OS) starting from initial TKI treatment and the T790M ctDNA status detected in plasma were analyzed. Among 318 patients, 117 who acquired TKI resistance were eligible for the analysis. T790M ctDNA was detected in the plasma of 55/117 (47%) patients. Almost half of the T790M ctDNA positive patients were identified at a median time of 2.2 months prior to clinically progressive disease (PD). Furthermore, within the patients receiving TKI treatment at 2(nd) line or later, the T790M ctDNA positive group had significantly shorter OS than the negative group (median OS: 26.9 months versus NA, P = 0.0489). Our study demonstrates the feasibility of monitoring EGFR mutation dynamics in serial plasma samples from NSCLC patients receiving TKI therapy. T790M ctDNA can be detected in plasma before and after PD as a poor prognostic factor. PMID:26867973

  19. Further evidence of Chelonid herpesvirus 5 (ChHV5) latency: high levels of ChHV5 DNA detected in clinically healthy marine turtles

    PubMed Central

    Bojesen, Anders Miki; Bertelsen, Mads F.; Wales, Nathan; Balazs, George H.; Gilbert, M. Thomas P.

    2016-01-01

    The Chelonid herpesvirus 5 (ChHV5) has been consistently associated with fibropapillomatosis (FP), a transmissible neoplastic disease of marine turtles. Whether ChHV5 plays a causal role remains debated, partly because while FP tumours have been clearly documented to contain high concentrations of ChHV5 DNA, recent PCR-based studies have demonstrated that large proportions of asymptomatic marine turtles are also carriers of ChHV5. We used a real-time PCR assay to quantify the levels of ChHV5 Glycoprotein B (gB) DNA in both tumour and non-tumour skin tissues, from clinically affected and healthy turtles drawn from distant ocean basins across four species. In agreement with previous studies, higher ratios of viral to host DNA were consistently observed in tumour versus non-tumour tissues in turtles with FP. Unexpectedly however, the levels of ChHV5 gB DNA in clinically healthy turtles were significantly higher than in non-tumour tissues from FP positive turtles. Thus, a large proportion of clinically healthy sea turtle populations worldwide across species carry ChHV5 gB DNA presumably through persistent latent infections. ChHV5 appears to be ubiquitous regardless of the animals’ clinical conditions. Hence, these results support the theory that ChHV5 is a near ubiquitous virus with latency characteristics requiring co-factors, possibly environmental or immune related, to induce FP. PMID:27547576

  20. Further evidence of Chelonid herpesvirus 5 (ChHV5) latency: high levels of ChHV5 DNA detected in clinically healthy marine turtles.

    PubMed

    Alfaro-Núñez, Alonzo; Bojesen, Anders Miki; Bertelsen, Mads F; Wales, Nathan; Balazs, George H; Gilbert, M Thomas P

    2016-01-01

    The Chelonid herpesvirus 5 (ChHV5) has been consistently associated with fibropapillomatosis (FP), a transmissible neoplastic disease of marine turtles. Whether ChHV5 plays a causal role remains debated, partly because while FP tumours have been clearly documented to contain high concentrations of ChHV5 DNA, recent PCR-based studies have demonstrated that large proportions of asymptomatic marine turtles are also carriers of ChHV5. We used a real-time PCR assay to quantify the levels of ChHV5 Glycoprotein B (gB) DNA in both tumour and non-tumour skin tissues, from clinically affected and healthy turtles drawn from distant ocean basins across four species. In agreement with previous studies, higher ratios of viral to host DNA were consistently observed in tumour versus non-tumour tissues in turtles with FP. Unexpectedly however, the levels of ChHV5 gB DNA in clinically healthy turtles were significantly higher than in non-tumour tissues from FP positive turtles. Thus, a large proportion of clinically healthy sea turtle populations worldwide across species carry ChHV5 gB DNA presumably through persistent latent infections. ChHV5 appears to be ubiquitous regardless of the animals' clinical conditions. Hence, these results support the theory that ChHV5 is a near ubiquitous virus with latency characteristics requiring co-factors, possibly environmental or immune related, to induce FP. PMID:27547576

  1. From DNA to Targeted Therapeutics: Bringing Synthetic Biology to the Clinic

    PubMed Central

    Chen, Yvonne Y.; Smolke, Christina D.

    2012-01-01

    Synthetic biology aims to make biological engineering more scalable and predictable, lowering the cost and facilitating the translation of synthetic biological systems to practical applications. Increasingly sophisticated, rationally designed synthetic systems that are capable of complex functions pave the way to translational applications, including disease diagnostics and targeted therapeutics. Here, we provide an overview of recent developments in synthetic biology in the context of translational research and discuss challenges at the interface between synthetic biology and clinical medicine. PMID:22030748

  2. Histogram-based classification with Gaussian mixture modeling for GBM tumor treatment response using ADC map

    NASA Astrophysics Data System (ADS)

    Huo, Jing; Kim, Hyun J.; Pope, Whitney B.; Okada, Kazunori; Alger, Jeffery R.; Wang, Yang; Goldin, Jonathan G.; Brown, Matthew S.

    2009-02-01

    This study applied a Gaussian Mixture Model (GMM) to apparent diffusion coefficient (ADC) histograms to evaluate glioblastoma multiforme (GBM) tumor treatment response using diffusion weighted (DW) MR images. ADC mapping, calculated from DW images, has been shown to reveal changes in the tumor's microenvironment preceding morphologic tumor changes. In this study, we investigated the effectiveness of features that represent changes from pre- and post-treatment tumor ADC histograms to detect treatment response. The main contribution of this work is to model the ADC histogram as the composition of two components, fitted by GMM with expectation maximization (EM) algorithm. For both pre- and post-treatment scans taken 5-7 weeks apart, we obtained the tumor ADC histogram, calculated the two-component features, as well as the other standard histogram-based features, and applied supervised learning for classification. We evaluated our approach with data from 85 patients with GBM under chemotherapy, in which 33 responded and 52 did not respond based on tumor size reduction. We compared AdaBoost and random forests classification algorithms, using ten-fold cross validation, resulting in a best accuracy of 69.41%.

  3. The L_infinity constrained global optimal histogram equalization technique for real time imaging

    NASA Astrophysics Data System (ADS)

    Ren, Qiongwei; Niu, Yi; Liu, Lin; Jiao, Yang; Shi, Guangming

    2015-08-01

    Although the current imaging sensors can achieve 12 or higher precision, the current display devices and the commonly used digital image formats are still only 8 bits. This mismatch causes significant waste of the sensor precision and loss of information when storing and displaying the images. For better usage of the precision-budget, tone mapping operators have to be used to map the high-precision data into low-precision digital images adaptively. In this paper, the classic histogram equalization tone mapping operator is reexamined in the sense of optimization. We point out that the traditional histogram equalization technique and its variants are fundamentally improper by suffering from local optimum problems. To overcome this drawback, we remodel the histogram equalization tone mapping task based on graphic theory which achieves the global optimal solutions. Another advantage of the graphic-based modeling is that the tone-continuity is also modeled as a vital constraint in our approach which suppress the annoying boundary artifacts of the traditional approaches. In addition, we propose a novel dynamic programming technique to solve the histogram equalization problem in real time. Experimental results shows that the proposed tone-preserved global optimal histogram equalization technique outperforms the traditional approaches by exhibiting more subtle details in the foreground while preserving the smoothness of the background.

  4. Value of MR histogram analyses for prediction of microvascular invasion of hepatocellular carcinoma

    PubMed Central

    Huang, Ya-Qin; Liang, He-Yue; Yang, Zhao-Xia; Ding, Ying; Zeng, Meng-Su; Rao, Sheng-Xiang

    2016-01-01

    Abstract The objective is to explore the value of preoperative magnetic resonance (MR) histogram analyses in predicting microvascular invasion (MVI) of hepatocellular carcinoma (HCC). Fifty-one patients with histologically confirmed HCC who underwent diffusion-weighted and contrast-enhanced MR imaging were included. Histogram analyses were performed and mean, variance, skewness, kurtosis, 1th, 10th, 50th, 90th, and 99th percentiles were derived. Quantitative histogram parameters were compared between HCCs with and without MVI. Receiver operating characteristics (ROC) analyses were generated to compare the diagnostic performance of tumor size, histogram analyses of apparent diffusion coefficient (ADC) maps, and MR enhancement. The mean, 1th, 10th, and 50th percentiles of ADC maps, and the mean, variance. 1th, 10th, 50th, 90th, and 99th percentiles of the portal venous phase (PVP) images were significantly different between the groups with and without MVI (P <0.05), with area under the ROC curves (AUCs) of 0.66 to 0.74 for ADC and 0.76 to 0.88 for PVP. The largest AUC of PVP (1th percentile) showed significantly higher accuracy compared with that of arterial phase (AP) or tumor size (P <0.001). MR histogram analyses—in particular for 1th percentile for PVP images—held promise for prediction of MVI of HCC. PMID:27368028

  5. Clinical activity and safety of the dual pathway inhibitor rigosertib for higher risk myelodysplastic syndromes following DNA methyltransferase inhibitor therapy.

    PubMed

    Silverman, Lewis R; Greenberg, Peter; Raza, Azra; Olnes, Matthew J; Holland, James F; Reddy, Premkumar; Maniar, Manoj; Wilhelm, Francois

    2015-06-01

    Rigosertib (ON 01910.Na) is an inhibitor of the phosphoinositide 3-kinase and polo-like kinase pathways that induces mitotic arrest and apoptosis in neoplastic cells, while sparing normal cells. Our purpose is to summarize the clinical activity and safety of intravenous (IV) rigosertib delivered by an external ambulatory infusion pump in patients with refractory anemia with excess blasts-1, -2, or, -t myelodysplastic syndromes (MDS) following prior treatment with DNA methyltransferase (DNMT) inhibitors. A total of 39 patients with MDS who fulfilled these criteria were enrolled in four phase 1-2 clinical trials of IV rigosertib. Thirty five (88%) had higher risk disease according to the Revised International Prognostic Scoring System. Median overall survival for this group of 39 patients was 35 weeks. Of 30 evaluable patients with follow-up bone marrow biopsies, 12 (40%) achieved complete (n = 5) or partial (n = 7) bone marrow blast responses. In addition, 15 patients achieved stabilization of bone marrow blasts. One patient with a complete bone marrow response also achieved a complete cytogenetic response. A second patient with stable bone marrow blasts achieved a partial cytogenetic response. Two of the responding patients and three patients with stable disease had hematological improvements. Rigosertib-induced bone marrow blast decreases and stability appeared to be predictive of prolonged survival. IV rigosertib had a favorable safety profile without significant myelosuppression. Most common drug-related toxicities included fatigue, diarrhea, nausea, dysuria, and hematuria. In summary, IV rigosertib is well tolerated and has clinical activity in patients with higher risk MDS following DNMT inhibitor treatment. A multinational pivotal phase 3 randomized clinical trial of rigosertib versus best supportive care for patients with MDS with excess blasts following prior treatment with DNMT inhibitors (ONTIME: ON 01910.Na Trial In Myelodysplastic SyndromE) has recently

  6. Dynamical Behavior of DNA

    NASA Astrophysics Data System (ADS)

    Kumar, Shankar

    1990-01-01

    The crystal structure of the DNA-EcoRI complex (Kim et al., 1990) revealed the existence of a 'kink' (or a disruption of the helical symmetry) in the DNA. Part of this work was an investigation of whether or not the kinked structure is a physically meaningful metastable state that is intrinsic to DNA. By using the "All Atom" hamiltonian of Weiner et al (1986) it has been found that the kink is not a metastable feature of the DNA. Rapid scanning of conformational space is indispensable in statistical mechanical studies of proteins and DNA. The Quasi-Optimized-Monte-Carlo (or QOMC) method is more efficient than the conventional Metropolis Monte Carlo method in the simulated annealing calculations reported here. It is also shown here that using altered masses in Molecular Dynamics calculations enhances sampling efficiency. The Multiple Histogram technique (Ferrenberg, 1989) has been applied for the first time on complex biomolecular hamiltonians. This method is superior to the classical perturbation and multistage sampling techniques for calculating free energy differences and generating potential of mean force profiles for suitably chosen reaction coordinates. This was demonstrated by using the multiple histogram method to generate the potential of mean force for the pseudorotation phase angle of the sugar ring in adenosine.

  7. Downregulation of ADAMTS8 by DNA Hypermethylation in Gastric Cancer and Its Clinical Significance

    PubMed Central

    Zhang, Jiakui; Li, Xin; Zhang, Chundong; Zhang, Hongbin; Jin, Junzhe; Dai, Dongqiu

    2016-01-01

    A disintegrin and metallopeptidase with thrombospondin motif type 8 (ADAMTS8), a member of the ADAMTS family, was discovered as a novel angiogenesis inhibitor. We analyzed the expression and methylation of ADAMTS8 in primary gastric tumors and gastric cancer cell lines. We also examined the relationship between ADAMTS8 expression and methylation and clinicopathologic features. The results showed that the significant downregulation of ADAMTS8 mRNA expression was observed in gastric cancer cell lines and tissues, and its expression was related to invasive depth and lymph node metastasis. CpG was hypermethylated in gastric cancer cell lines MKN45, MGC803, and BGC823, as well as primary gastric cancer specimens. ADAMTS8 mRNA expression was significantly lower in methylated primary gastric tumors. A significant association was found between ADAMTS8 methylation status and lymph node metastasis in primary gastric cancer. Moreover, ADAMTS8 expression was upregulated in the gastric cancer cell lines MGC803, BGC823, and MKN45 after treatment with 5-aza-2′-deoxycytidine. Thus, our results demonstrate that expression of ADAMTS8 mRNA is significantly decreased and DNA methylation is frequent in gastric cancer. ADAMTS8 hypermethylation is associated with decreased expression in gastric cancer and may play an important role in the invasion and metastasis of gastric cancer. PMID:27493958

  8. DNA methylation fingerprint of neuroblastoma reveals new biological and clinical insights

    PubMed Central

    Gómez, Soledad; Castellano, Giancarlo; Mayol, Gemma; Queiros, Ana; Martín-Subero, José I.; Lavarino, Cinzia

    2015-01-01

    Neuroblastoma (NB) is one of the most frequently occurring extracranial solid tumors of childhood (Maris et al., 2007 [1]; Brodeur, 2003 [2]). Probability of cure varies according to patient's age, extent of disease and tumor biology (Maris et al., 2007 [1]; Brodeur, 2003 [2]; Cohn et al., 2009 [3]). However, the etiology of this developmental tumor is unknown. Recent evidence has shown that pediatric solid tumors, including NB, harbor a paucity of recurrent genetic mutations, with a significant proportion of recurrent events converging on epigenetic mechanisms (Cheung et al., 2012 [4]; Molenaar et al., 2012 [5]; Pugh et al., 2013 [6]; Sausen et al., 2013 [7]. We have analyzed the DNA methylome of neuroblastoma using high-density microarrays (Infinium Human Methylation 450k BeadChip) to define the epigenetic landscape of this pediatric tumor and its potential clinicopathological impact. Here, we provide the detail of methods and quality control parameters of the microarray data used for the study. Methylation data has been deposited at NCBI Gene Expression Omnibus data repository, accession number GSE54719; superseries record GSE54721. PMID:26484286

  9. Infrared face recognition based on LBP histogram and KW feature selection

    NASA Astrophysics Data System (ADS)

    Xie, Zhihua

    2014-07-01

    The conventional LBP-based feature as represented by the local binary pattern (LBP) histogram still has room for performance improvements. This paper focuses on the dimension reduction of LBP micro-patterns and proposes an improved infrared face recognition method based on LBP histogram representation. To extract the local robust features in infrared face images, LBP is chosen to get the composition of micro-patterns of sub-blocks. Based on statistical test theory, Kruskal-Wallis (KW) feature selection method is proposed to get the LBP patterns which are suitable for infrared face recognition. The experimental results show combination of LBP and KW features selection improves the performance of infrared face recognition, the proposed method outperforms the traditional methods based on LBP histogram, discrete cosine transform(DCT) or principal component analysis(PCA).

  10. Perceived quality of wood images influenced by the skewness of image histogram

    NASA Astrophysics Data System (ADS)

    Katsura, Shigehito; Mizokami, Yoko; Yaguchi, Hirohisa

    2015-08-01

    The shape of image luminance histograms is related to material perception. We investigated how the luminance histogram contributed to improvements in the perceived quality of wood images by examining various natural wood and adhesive vinyl sheets with printed wood grain. In the first experiment, we visually evaluated the perceived quality of wood samples. In addition, we measured the colorimetric parameters of the wood samples and calculated statistics of image luminance. The relationship between visual evaluation scores and image statistics suggested that skewness and kurtosis affected the perceived quality of wood. In the second experiment, we evaluated the perceived quality of wood images with altered luminance skewness and kurtosis using a paired comparison method. Our result suggests that wood images are more realistic if the skewness of the luminance histogram is slightly negative.

  11. [Image Feature Extraction and Discriminant Analysis of Xinjiang Uygur Medicine Based on Color Histogram].

    PubMed

    Hamit, Murat; Yun, Weikang; Yan, Chuanbo; Kutluk, Abdugheni; Fang, Yang; Alip, Elzat

    2015-06-01

    Image feature extraction is an important part of image processing and it is an important field of research and application of image processing technology. Uygur medicine is one of Chinese traditional medicine and researchers pay more attention to it. But large amounts of Uygur medicine data have not been fully utilized. In this study, we extracted the image color histogram feature of herbal and zooid medicine of Xinjiang Uygur. First, we did preprocessing, including image color enhancement, size normalizition and color space transformation. Then we extracted color histogram feature and analyzed them with statistical method. And finally, we evaluated the classification ability of features by Bayes discriminant analysis. Experimental results showed that high accuracy for Uygur medicine image classification was obtained by using color histogram feature. This study would have a certain help for the content-based medical image retrieval for Xinjiang Uygur medicine. PMID:26485983

  12. Fluorescent image classification by major color histograms and a neural network

    NASA Astrophysics Data System (ADS)

    Soriano, M.; Garcia, L.; Saloma, Caesar A.

    2001-02-01

    Efficient image classification of microscopic fluorescent spheres is demonstrated with a supervised backpropagation neural network (NN) that uses as inputs the major color histogram representation of the fluorescent image to be classified. Two techniques are tested for the major color search: (1) cluster mean (CM) and (2) Kohonen's self-organizing feature map (SOFM). The method is shown to have higher recognition rates than Swain and Ballard's Color Indexing by histogram intersection. Classification with SOFM-generated histograms as inputs to the classifier NN achieved the best recognition rate (90%) for cases of normal, scaled, defocused, photobleached, and combined images of AMCA (7-Amino-4-Methylcoumarin- 3-Acetic Acid) and FITC (Fluorescein Isothiocynate)-stained microspheres.

  13. Molecular Identification of Clinical Isolates of Mycobacterium fortuitum by Random Amplified Polymorphic DNA (RAPD) Polymerase Chain Reaction and ERIC PCR

    PubMed Central

    Khosravi, Azar Dokht; Farahani, Abbas; Jamali, Hooshang

    2015-01-01

    Backgrounds Non tuberculous mycobacteria (NTM) are of importance now-a-days due to their increasing virulence outbreaks and emerging antibiotic resistance. Since the most common NTM in Iran is reportedly Mycobacterium fortuitum, the present study was designed with the aim of molecular identification of clinical isolates of M. foruitum to analyse their heterogeneity. Materials and Methods A total of 81 isolates of NTM isolated from various samples were collected. The clinical isolates were assigned to species M. fortuitum by using conventional and molecular methods. The DNA banding patterns of ERIC- PCR and RAPD- PCR were analysed by using Bionumeric 7.5 software. Results Out of 81 tested NTM, 36 strains of M. fortuitum were identified. 33 isolates were selected for molecular typing in this study. Based on RAPD and ERIC analysis, M. fortuitum isolates were divided into 3 and 6 clusters, respectively. Most of the isolates were distributed into types of II RAPD (20 members/ 60.6 %) and V (14 members/ 42.4% with sub cluster I & II) of ERIC. In RAPD analysis, the major fragments were 300 bp, followed by fragment 1000. In ERIC analysis, the major fragments were 280 bp followed by fragment 1200 bp. Conclusion In conclusion, though the results from this study represented higher discriminatory power of ERIC, however the combination of RAPD and ERIC analysis were able to sufficiently discriminate the genotypic diversity, infection control, and gain useful epidemiological information regarding M. fortuitum isolates. PMID:26816886

  14. Adapting histogram for automatic noise data removal in building interior point cloud data

    NASA Astrophysics Data System (ADS)

    Shukor, S. A. Abdul; Rushforth, E. J.

    2015-05-01

    3D point cloud data is now preferred by researchers to generate 3D models. These models can be used throughout a variety of applications including 3D building interior models. The rise of Building Information Modeling (BIM) for Architectural, Engineering, Construction (AEC) applications has given 3D interior modelling more attention recently. To generate a 3D model representing the building interior, a laser scanner is used to collect the point cloud data. However, this data often comes with noise. This is due to several factors including the surrounding objects, lighting and specifications of the laser scanner. This paper highlights on the usage of the histogram to remove the noise data. Histograms, used in statistics and probability, are regularly being used in a number of applications like image processing, where a histogram can represent the total number of pixels in an image at each intensity level. Here, histograms represent the number of points recorded at range distance intervals in various projections. As unwanted noise data has a sparser cloud density compared to the required data and is usually situated at a notable distance from the required data, noise data will have lower frequencies in the histogram. By defining the acceptable range using the average frequency, points below this range can be removed. This research has shown that these histograms have the capabilities to remove unwanted data from 3D point cloud data representing building interiors automatically. This feature will aid the process of data preprocessing in producing an ideal 3D model from the point cloud data.

  15. Enhanced optical coherence tomography imaging using a histogram-based denoising algorithm

    NASA Astrophysics Data System (ADS)

    Kim, Keo-Sik; Park, Hyoung-Jun; Kang, Hyun Seo

    2015-11-01

    A histogram-based denoising algorithm was developed to effectively reduce ghost artifact noise and enhance the quality of an optical coherence tomography (OCT) imaging system used to guide surgical instruments. The noise signal is iteratively detected by comparing the histogram of the ensemble average of all A-scans, and the ghost artifacts included in the noisy signal are removed separately from the raw signals using the polynomial curve fitting method. The devised algorithm was simulated with various noisy OCT images, and >87% of the ghost artifact noise was removed despite different locations. Our results show the feasibility of selectively and effectively removing ghost artifact noise.

  16. Ear segmentation using histogram based K-means clustering and Hough transformation under CVL dataset

    NASA Astrophysics Data System (ADS)

    Liu, Heng; Liu, Dekai

    2009-10-01

    Under CVL dataset, we provide an image segmentation approach based on adaptive histogram based K-means clustering and fast Hough transformation. This work firstly analyzes the characteristics of ear images in CVL face dataset. According to the analysis, we then use adaptive histogram based K-means clustering method to threshold ear images and then roughly segment the ear parts. After ear contour extraction, with boundary determination through vertical project, Hough transformation is utilized to locate the ear contour accurately. The experimental results and comparisons with other segmentation methods show our approach is effective.

  17. Brief Communication: Contrast-stretching- and histogram-smoothness-based synthetic aperture radar image enhancement for flood map generation

    NASA Astrophysics Data System (ADS)

    Nazir, F.; Riaz, M. M.; Ghafoor, A.; Arif, F.

    2015-02-01

    Synthetic-aperture-radar-image-based flood map generation is usually a challenging task (due to degraded contrast). A three-step approach (based on adaptive histogram clipping, histogram remapping and smoothing) is proposed for generation of a more visualized flood map image. The pre- and post-flood images are adaptively histogram equalized. The hidden details in difference image are enhanced using contrast-based enhancement and histogram smoothing. A fast-ready flood map is then generated using equalized pre-, post- and difference images. Results (evaluated using different data sets) show significance of the proposed technique.

  18. DNA Microarrays: a Powerful Genomic Tool for Biomedical and Clinical Research

    PubMed Central

    Trevino, Victor; Falciani, Francesco; Barrera-Saldaña, Hugo A

    2007-01-01

    Among the many benefits of the Human Genome Project are new and powerful tools such as the genome-wide hybridization devices referred to as microarrays. Initially designed to measure gene transcriptional levels, microarray technologies are now used for comparing other genome features among individuals and their tissues and cells. Results provide valuable information on disease subcategories, disease prognosis, and treatment outcome. Likewise, they reveal differences in genetic makeup, regulatory mechanisms, and subtle variations and move us closer to the era of personalized medicine. To understand this powerful tool, its versatility, and how dramatically it is changing the molecular approach to biomedical and clinical research, this review describes the technology, its applications, a didactic step-by-step review of a typical microarray protocol, and a real experiment. Finally, it calls the attention of the medical community to the importance of integrating multidisciplinary teams to take advantage of this technology and its expanding applications that, in a slide, reveals our genetic inheritance and destiny. PMID:17660860

  19. A Phase 1 clinical trial of a DNA vaccine for Venezuelan equine encephalitis delivered by intramuscular or intradermal electroporation.

    PubMed

    Hannaman, Drew; Dupuy, Lesley C; Ellefsen, Barry; Schmaljohn, Connie S

    2016-06-30

    Venezuelan equine encephalitis virus (VEEV), a mosquito-borne alphavirus, causes periodic epizootics in equines and is a recognized biological defense threat for humans. There are currently no FDA-licensed vaccines against VEEV. We developed a candidate DNA vaccine expressing the E3-E2-6K-E1 genes of VEEV (pWRG/VEE) and performed a Phase 1 clinical study to assess the vaccine's safety, reactogenicity, tolerability, and immunogenicity when administered by intramuscular (IM) or intradermal (ID) electroporation (EP) using the Ichor Medical Systems TriGrid™ Delivery System. Subjects in IM-EP groups received 0.5mg (N=8) or 2.0mg (N=9) of pWRG/VEE or a saline placebo (N=4) in a 1.0ml injection. Subjects in ID-EP groups received 0.08mg (N=8) or 0.3mg (N=8) of DNA or a saline placebo (N=4) in a 0.15ml injection. Subjects were monitored for a total period of 360 days. No vaccine- or device-related serious adverse events were reported. Based on the results of a subject questionnaire, the IM- and ID-EP procedures were both considered to be generally acceptable for prophylactic vaccine administration, with the acute tolerability of ID EP delivery judged to be greater than that of IM-EP delivery. All subjects (100%) in the high and low dose IM-EP groups developed detectable VEEV-neutralizing antibodies after two or three administrations of pWRG/VEE, respectively. VEEV-neutralizing antibody responses were detected in seven of eight subjects (87.5%) in the high dose and five of eight subjects (62.5%) in the low dose ID-EP groups after three vaccine administrations. There was a correlation between the DNA dose and the magnitude of the resulting VEEV-neutralizing antibody responses for both IM and ID EP delivery. These results indicate that pWRG/VEE delivered by either IM- or ID-EP is safe, tolerable, and immunogenic in humans at the evaluated dose levels. Clinicaltrials.gov registry number NCT01984983. PMID:27206386

  20. DIF Testing with an Empirical-Histogram Approximation of the Latent Density for Each Group

    ERIC Educational Resources Information Center

    Woods, Carol M.

    2011-01-01

    This research introduces, illustrates, and tests a variation of IRT-LR-DIF, called EH-DIF-2, in which the latent density for each group is estimated simultaneously with the item parameters as an empirical histogram (EH). IRT-LR-DIF is used to evaluate the degree to which items have different measurement properties for one group of people versus…

  1. Comparison Between Cooccurrence Matrices, Local Histograms And Curvilinear Integration For Texture Characterization

    NASA Astrophysics Data System (ADS)

    Ronsin, J.; Barba, D.; Raboisson, S.

    1986-04-01

    We present an algorithm for texture characterization based upon curvilinear integration of grey tone signal along some predefined directions.In the context of image segmentation, we compare the performances of this very simple technique with two other ones : texture features by second-order cooccurrence probabilities, and texture features by local one dimensional histograms. Good classification performances are obtained on quite different pictures.

  2. Reducing variability in the output of pattern classifiers using histogram shaping

    SciTech Connect

    Gupta, Shalini; Kan, Chih-Wen; Markey, Mia K.

    2010-04-15

    Purpose: The authors present a novel technique based on histogram shaping to reduce the variability in the output and (sensitivity, specificity) pairs of pattern classifiers with identical ROC curves, but differently distributed outputs. Methods: The authors identify different sources of variability in the output of linear pattern classifiers with identical ROC curves, which also result in classifiers with differently distributed outputs. They theoretically develop a novel technique based on the matching of the histograms of these differently distributed pattern classifier outputs to reduce the variability in their (sensitivity, specificity) pairs at fixed decision thresholds, and to reduce the variability in their actual output values. They empirically demonstrate the efficacy of the proposed technique by means of analyses on the simulated data and real world mammography data. Results: For the simulated data, with three different known sources of variability, and for the real world mammography data with unknown sources of variability, the proposed classifier output calibration technique significantly reduced the variability in the classifiers' (sensitivity, specificity) pairs at fixed decision thresholds. Furthermore, for classifiers with monotonically or approximately monotonically related output variables, the histogram shaping technique also significantly reduced the variability in their actual output values. Conclusions: Classifier output calibration based on histogram shaping can be successfully employed to reduce the variability in the output values and (sensitivity, specificity) pairs of pattern classifiers with identical ROC curves, but differently distributed outputs.

  3. Estimating the body portion of CT volumes by matching histograms of visual words

    NASA Astrophysics Data System (ADS)

    Feulner, Johannes; Zhou, S. Kevin; Seifert, Sascha; Cavallaro, Alexander; Hornegger, Joachim; Comaniciu, Dorin

    2009-02-01

    Being able to automatically determine which portion of the human body is shown by a CT volume image offers various possibilities like automatic labeling of images or initializing subsequent image analysis algorithms. This paper presents a method that takes a CT volume as input and outputs the vertical body coordinates of its top and bottom slice in a normalized coordinate system whose origin and unit length are determined by anatomical landmarks. Each slice of a volume is described by a histogram of visual words: Feature vectors consisting of an intensity histogram and a SURF descriptor are first computed on a regular grid and then classified into the closest visual words to form a histogram. The vocabulary of visual words is a quantization of the feature space by offline clustering a large number of feature vectors from prototype volumes into visual words (or cluster centers) via the K-Means algorithm. For a set of prototype volumes whose body coordinates are known the slice descriptions are computed in advance. The body coordinates of a test volume are computed by a 1D rigid registration of the test volume with the prototype volumes in axial direction. The similarity of two slices is measured by comparing their histograms of visual words. Cross validation on a dataset of 44 volumes proved the robustness of the results. Even for test volumes of ca. 20cm height, the average error was 15.8mm.

  4. A contrast correction method for dental images based on histogram registration

    PubMed Central

    Economopoulos, TL; Asvestas, PA; Matsopoulos, GK; Gröndahl, K; Gröndahl, H-G

    2010-01-01

    Contrast correction is often required in digital subtraction radiography when comparing medical data acquired over different time periods owing to dissimilarities in the acquisition process. This paper focuses on dental radiographs and introduces a novel approach for correcting the contrast in dental image pairs. The proposed method modifies the subject images by applying typical registration techniques on their histograms. The proposed histogram registration method reshapes the histograms of the two subject images in such a way that these images are matched in terms of their contrast deviation. The method was extensively tested over 4 sets of dental images, consisting of 72 registered dental image pairs with unknown contrast differences as well as 20 dental pairs with known contrast differences. The proposed method was directly compared against the well-known histogram-based contrast correction method. The two methods were qualitatively and quantitatively evaluated for all 92 available dental image pairs. The two methods were compared in terms of the contrast root mean square difference between the reference image and the corrected image in each case. The obtained results were also verified statistically using appropriate t-tests in each set. The proposed method exhibited superior performance compared with the well-established method, in terms of the contrast root mean square difference between the reference and the corrected images. After suitable statistical analysis, it was deduced that the performance advantage of the proposed approach was statistically significant. PMID:20587655

  5. Pattern-histogram-based temporal change detection using personal chest radiographs

    NASA Astrophysics Data System (ADS)

    Ugurlu, Yucel; Obi, Takashi; Hasegawa, Akira; Yamaguchi, Masahiro; Ohyama, Nagaaki

    1999-05-01

    An accurate and reliable detection of temporal changes from a pair of images has considerable interest in the medical science. Traditional registration and subtraction techniques can be applied to extract temporal differences when,the object is rigid or corresponding points are obvious. However, in radiological imaging, loss of the depth information, the elasticity of object, the absence of clearly defined landmarks and three-dimensional positioning differences constraint the performance of conventional registration techniques. In this paper, we propose a new method in order to detect interval changes accurately without using an image registration technique. The method is based on construction of so-called pattern histogram and comparison procedure. The pattern histogram is a graphic representation of the frequency counts of all allowable patterns in the multi-dimensional pattern vector space. K-means algorithm is employed to partition pattern vector space successively. Any differences in the pattern histograms imply that different patterns are involved in the scenes. In our experiment, a pair of chest radiographs of pneumoconiosis is employed and the changing histogram bins are visualized on both of the images. We found that the method can be used as an alternative way of temporal change detection, particularly when the precise image registration is not available.

  6. Large-Scale Merging of Histograms using Distributed In-Memory Computing

    NASA Astrophysics Data System (ADS)

    Blomer, Jakob; Ganis, Gerardo

    2015-12-01

    Most high-energy physics analysis jobs are embarrassingly parallel except for the final merging of the output objects, which are typically histograms. Currently, the merging of output histograms scales badly. The running time for distributed merging depends not only on the overall number of bins but also on the number partial histogram output files. That means, while the time to analyze data decreases linearly with the number of worker nodes, the time to merge the histograms in fact increases with the number of worker nodes. On the grid, merging jobs that take a few hours are not unusual. In order to improve the situation, we present a distributed and decentral merging algorithm whose running time is independent of the number of worker nodes. We exploit full bisection bandwidth of local networks and we keep all intermediate results in memory. We present benchmarks from an implementation using the parallel ROOT facility (PROOF) and RAMCloud, a distributed key-value store that keeps all data in DRAM.

  7. Utility of histogram analysis of ADC maps for differentiating orbital tumors

    PubMed Central

    Xu, Xiao-Quan; Hu, Hao; Su, Guo-Yi; Liu, Hu; Hong, Xun-Ning; Shi, Hai-Bin; Wu, Fei-Yun

    2016-01-01

    PURPOSE We aimed to evaluate the role of histogram analysis of apparent diffusion coefficient (ADC) maps for differentiating benign and malignant orbital tumors. METHODS Fifty-two patients with orbital tumors were enrolled from March 2013 to November 2014. Pretreatment diffusion-weighted imaging was performed on a 3T magnetic resonance scanner with b factors of 0 and 800 s/mm2, and the corresponding ADC maps were generated. Whole-tumor regions of interest were drawn on all slices of the ADC maps to obtain histogram parameters, including ADCmean, ADCmedian, standard deviation (SD), skewness, kurtosis, quartile, ADC10, ADC25, ADC75, and ADC90. Histogram parameter differences between benign and malignant orbital tumors were compared. The diagnostic value of each significant parameter in predicting malignant tumors was established. RESULTS Age, ADCmean, ADCmedian, quartile, kurtosis, ADC10, ADC25, ADC75, and ADC90 parameters were significantly different between benign and malignant orbital tumor groups, while gender, location, SD, and skewness were not significantly different. The best diagnostic performance in predicting malignant orbital tumors was achieved at the threshold of ADC10=0.990 (AUC, 0.997; sensitivity, 96.2%; specificity, 100%). CONCLUSION Histogram analysis of ADC maps holds promise for differentiating benign and malignant orbital tumors. ADC10 has the potential to be the most significant parameter for predicting malignant orbital tumors. PMID:26829400

  8. Human detection by quadratic classification on subspace of extended histogram of gradients.

    PubMed

    Satpathy, Amit; Jiang, Xudong; Eng, How-Lung

    2014-01-01

    This paper proposes a quadratic classification approach on the subspace of Extended Histogram of Gradients (ExHoG) for human detection. By investigating the limitations of Histogram of Gradients (HG) and Histogram of Oriented Gradients (HOG), ExHoG is proposed as a new feature for human detection. ExHoG alleviates the problem of discrimination between a dark object against a bright background and vice versa inherent in HG. It also resolves an issue of HOG whereby gradients of opposite directions in the same cell are mapped into the same histogram bin. We reduce the dimensionality of ExHoG using Asymmetric Principal Component Analysis (APCA) for improved quadratic classification. APCA also addresses the asymmetry issue in training sets of human detection where there are much fewer human samples than non-human samples. Our proposed approach is tested on three established benchmarking data sets--INRIA, Caltech, and Daimler--using a modified Minimum Mahalanobis distance classifier. Results indicate that the proposed approach outperforms current state-of-the-art human detection methods. PMID:23708804

  9. Efficient visibility-driven medical image visualisation via adaptive binned visibility histogram.

    PubMed

    Jung, Younhyun; Kim, Jinman; Kumar, Ashnil; Feng, David Dagan; Fulham, Michael

    2016-07-01

    'Visibility' is a fundamental optical property that represents the observable, by users, proportion of the voxels in a volume during interactive volume rendering. The manipulation of this 'visibility' improves the volume rendering processes; for instance by ensuring the visibility of regions of interest (ROIs) or by guiding the identification of an optimal rendering view-point. The construction of visibility histograms (VHs), which represent the distribution of all the visibility of all voxels in the rendered volume, enables users to explore the volume with real-time feedback about occlusion patterns among spatially related structures during volume rendering manipulations. Volume rendered medical images have been a primary beneficiary of VH given the need to ensure that specific ROIs are visible relative to the surrounding structures, e.g. the visualisation of tumours that may otherwise be occluded by neighbouring structures. VH construction and its subsequent manipulations, however, are computationally expensive due to the histogram binning of the visibilities. This limits the real-time application of VH to medical images that have large intensity ranges and volume dimensions and require a large number of histogram bins. In this study, we introduce an efficient adaptive binned visibility histogram (AB-VH) in which a smaller number of histogram bins are used to represent the visibility distribution of the full VH. We adaptively bin medical images by using a cluster analysis algorithm that groups the voxels according to their intensity similarities into a smaller subset of bins while preserving the distribution of the intensity range of the original images. We increase efficiency by exploiting the parallel computation and multiple render targets (MRT) extension of the modern graphical processing units (GPUs) and this enables efficient computation of the histogram. We show the application of our method to single-modality computed tomography (CT), magnetic resonance

  10. [Fractal dimension and histogram method: algorithm and some preliminary results of noise-like time series analysis].

    PubMed

    Pancheliuga, V A; Pancheliuga, M S

    2013-01-01

    In the present work a methodological background for the histogram method of time series analysis is developed. Connection between shapes of smoothed histograms constructed on the basis of short segments of time series of fluctuations and the fractal dimension of the segments is studied. It is shown that the fractal dimension possesses all main properties of the histogram method. Based on it a further development of fractal dimension determination algorithm is proposed. This algorithm allows more precision determination of the fractal dimension by using the "all possible combination" method. The application of the method to noise-like time series analysis leads to results, which could be obtained earlier only by means of the histogram method based on human expert comparisons of histograms shapes. PMID:23755565

  11. Histogram and gray level co-occurrence matrix on gray-scale ultrasound images for diagnosing lymphocytic thyroiditis.

    PubMed

    Shin, Young Gyung; Yoo, Jaeheung; Kwon, Hyeong Ju; Hong, Jung Hwa; Lee, Hye Sun; Yoon, Jung Hyun; Kim, Eun-Kyung; Moon, Hee Jung; Han, Kyunghwa; Kwak, Jin Young

    2016-08-01

    The objective of the study was to evaluate whether texture analysis using histogram and gray level co-occurrence matrix (GLCM) parameters can help clinicians diagnose lymphocytic thyroiditis (LT) and differentiate LT according to pathologic grade. The background thyroid pathology of 441 patients was classified into no evidence of LT, chronic LT (CLT), and Hashimoto's thyroiditis (HT). Histogram and GLCM parameters were extracted from the regions of interest on ultrasound. The diagnostic performances of the parameters for diagnosing and differentiating LT were calculated. Of the histogram and GLCM parameters, the mean on histogram had the highest Az (0.63) and VUS (0.303). As the degrees of LT increased, the mean decreased and the standard deviation and entropy increased. The mean on histogram from gray-scale ultrasound showed the best diagnostic performance as a single parameter in differentiating LT according to pathologic grade as well as in diagnosing LT. PMID:27336835

  12. Early epigenetic changes and DNA damage do not predict clinical response in an overlapping schedule of 5-azacytidine and entinostat in patients with myeloid malignancies

    PubMed Central

    Fandy, Tamer E.; Herman, James G.; Kerns, Patrick; Jiemjit, Anchalee; Sugar, Elizabeth A.; Choi, Si-Ho; Yang, Allen S.; Aucott, Timothy; Dauses, Tianna; Odchimar-Reissig, Rosalie; Licht, Jonathan; McConnell, Melanie J.; Nasrallah, Chris; Kim, Marianne K. H.; Zhang, Weijia; Sun, Yezou; Murgo, Anthony; Espinoza-Delgado, Igor; Oteiza, Katharine; Owoeye, Ibitayo; Silverman, Lewis R.; Carraway, Hetty E.

    2009-01-01

    Sequential administration of DNA methyltransferase (DNMT) inhibitors and histone deacetylase (HDAC) inhibitors has demonstrated clinical efficacy in patients with hematologic malignancies. However, the mechanism behind their clinical efficacy remains controversial. In this study, the methylation dynamics of 4 TSGs (p15INK4B, CDH-1, DAPK-1, and SOCS-1) were studied in sequential bone marrow samples from 30 patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) who completed a minimum of 4 cycles of therapy with 5-azacytidine and entinostat. Reversal of promoter methylation after therapy was observed in both clinical responders and nonresponders across all genes. There was no association between clinical response and either baseline methylation or methylation reversal in the bone marrow or purified CD34+ population, nor was there an association with change in gene expression. Transient global hypomethylation was observed in samples after treatment but was not associated with clinical response. Induction of histone H3/H4 acetylation and the DNA damage–associated variant histone γ-H2AX was observed in peripheral blood samples across all dose cohorts. In conclusion, methylation reversal of candidate TSGs during cycle 1 of therapy was not predictive of clinical response to combination “epigenetic” therapy. This trial is registered with http://www.clinicaltrials.gov under NCT00101179. PMID:19546476

  13. Clinical and biological significance of RAD51 expression in breast cancer: a key DNA damage response protein.

    PubMed

    Alshareeda, Alaa Tarig; Negm, Ola H; Aleskandarany, Mohammed A; Green, Andrew R; Nolan, Christopher; TigHhe, Patrick J; Madhusudan, Srinivasan; Ellis, Ian O; Rakha, Emad A

    2016-08-01

    Impaired DNA damage response (DDR) may play a fundamental role in the pathogenesis of breast cancer (BC). RAD51 is a key player in DNA double-strand break repair. In this study, we aimed to assess the biological and clinical significance of RAD51 expression with relevance to different molecular classes of BC and patients' outcome. The expression of RAD51 was assessed immunohistochemically in a well-characterised annotated series (n = 1184) of early-stage invasive BC with long-term follow-up. A subset of cases of BC from patients with known BRCA1 germline mutations was included as a control group. The results were correlated with clinicopathological and molecular parameters and patients' outcome. RAD51 protein expression level was also assayed in a panel of cell lines using reverse phase protein array (RPPA). RAD51 was expressed in the nuclei (N) and cytoplasm (C) of malignant cells. Subcellular co-localisation phenotypes of RAD51 were significantly associated with clinicopathological features and patient outcome. Cytoplasmic expression (RAD51C(+)) and lack of nuclear expression (RAD51 N(-)) were associated with features of aggressive behaviour, including larger tumour size, high grade, lymph nodal metastasis, basal-like, and triple-negative phenotypes, together with aberrant expression of key DDR biomarkers including BRCA1. All BRCA1-mutated tumours had RAD51C(+)/N(-) phenotype. RPPA confirmed IHC results and showed differential expression of RAD51 in cell lines based on ER expression and BRCA1 status. RAD51 N(+) and RAD51C(+) tumours were associated with longer and shorter breast cancer-specific survival (BCSS), respectively. The RAD51 N(+) was an independent predictor of longer BCSS (P < 0.0001). Lack of RAD51 nuclear expression is associated with poor prognostic parameters and shorter survival in invasive BC patients. The significant associations between RAD51 subcellular localisation and clinicopathological features, molecular subtype and patients

  14. Reduced XPC DNA repair gene mRNA levels in clinically normal parents of xeroderma pigmentosum patients.

    PubMed

    Khan, Sikandar G; Oh, Kyu-Seon; Shahlavi, Tala; Ueda, Takahiro; Busch, David B; Inui, Hiroki; Emmert, Steffen; Imoto, Kyoko; Muniz-Medina, Vanessa; Baker, Carl C; DiGiovanna, John J; Schmidt, Deborah; Khadavi, Arash; Metin, Ahmet; Gozukara, Engin; Slor, Hanoch; Sarasin, Alain; Kraemer, Kenneth H

    2006-01-01

    Xeroderma pigmentosum group C (XP-C) is a rare autosomal recessive disorder. Patients with two mutant alleles of the XPC DNA repair gene have sun sensitivity and a 1000-fold increase in skin cancers. Clinically normal parents of XP-C patients have one mutant allele and one normal allele. As a step toward evaluating cancer risk in these XPC heterozygotes we characterized cells from 16 XP families. We identified 15 causative mutations (5 frameshift, 6 nonsense and 4 splicing) in the XPC gene in cells from 16 XP probands. All had premature termination codons (PTC) and absence of normal XPC protein on western blotting. The cell lines from 26 parents were heterozygous for the same mutations. We employed a real-time quantitative reverse transcriptase-PCR assay as a rapid and sensitive method to measure XPC mRNA levels. The mean XPC mRNA levels in the cell lines from the XP-C probands were 24% (P<10(-7)) of that in 10 normal controls. This reduced XPC mRNA level in cells from XP-C patients was caused by the PTC that induces nonsense-mediated mRNA decay. The mean XPC mRNA levels in cell lines from the heterozygous XP-C carriers were intermediate (59%, P=10(-4)) between the values for the XP patients and the normal controls. This study demonstrates reduced XPC mRNA levels in XP-C patients and heterozygotes. Thus, XPC mRNA levels may be evaluated as a marker of cancer susceptibility in carriers of mutations in the XPC gene. PMID:16081512

  15. Optical performance monitoring technique using software-based synchronous amplitude histograms.

    PubMed

    Choi, H G; Chang, J H; Kim, Hoon; Chung, Y C

    2014-10-01

    We propose and demonstrate a simple technique to monitor both the optical signal-to-noise ratio (OSNR) and chromatic dispersion (CD) by using the software-based synchronous amplitude histogram (SAH) analysis. We exploit the software-based synchronization technique to construct SAHs from the asynchronously sampled intensities of the signal. The use of SAHs facilitates the accurate extraction of the monitoring parameters at the center of the symbol. Thus, unlike in the case of using the technique based on the asynchronous amplitude histogram (AAH), this technique is not affected by the transient characteristics of the modulated signals. The performance of the proposed monitoring technique is evaluated experimentally by using 10-Gbaud quadrature phase-shift keying (QPSK) and quadrature amplitude modulation (QAM) signals over wide ranges of OSNR and CD. We also evaluate the robustness of the proposed technique to the signal's transient characteristics. PMID:25321978

  16. High Capacity Reversible Watermarking for Audio by Histogram Shifting and Predicted Error Expansion

    PubMed Central

    Wang, Fei; Chen, Zuo

    2014-01-01

    Being reversible, the watermarking information embedded in audio signals can be extracted while the original audio data can achieve lossless recovery. Currently, the few reversible audio watermarking algorithms are confronted with following problems: relatively low SNR (signal-to-noise) of embedded audio; a large amount of auxiliary embedded location information; and the absence of accurate capacity control capability. In this paper, we present a novel reversible audio watermarking scheme based on improved prediction error expansion and histogram shifting. First, we use differential evolution algorithm to optimize prediction coefficients and then apply prediction error expansion to output stego data. Second, in order to reduce location map bits length, we introduced histogram shifting scheme. Meanwhile, the prediction error modification threshold according to a given embedding capacity can be computed by our proposed scheme. Experiments show that this algorithm improves the SNR of embedded audio signals and embedding capacity, drastically reduces location map bits length, and enhances capacity control capability. PMID:25097883

  17. Liver fibrosis grading using multiresolution histogram information in real-time elastography

    NASA Astrophysics Data System (ADS)

    Albouy-Kissi, A.; Sarry, L.; Massoulier, S.; Bonny, C.; Randl, K.; Abergel, A.

    2010-03-01

    Despites many limitations, liver biopsy remains the gold standard method for grading and staging liver biopsy. Several modalities have been developed for a non invasive assessment of liver diseases. Real-time elastography may constitute a true alternative to liver biopsy by providing an image of tissular elasticity distribution correlated to the fibrosis grade. In this paper, we investigate a new approach for the assessment of liver fibrosis by the classification of fibrosis morphometry. Multiresolution histogram, based on a combination of intensity and texture features, has been tested as feature space. Thus, the ability of such multiresolution histograms to discriminate fibrosis grade has been proven. The results have been tested on seventeen patients that underwent a real time elastography and FibroScan examination.

  18. Analytical and Clinical Validation of a Digital Sequencing Panel for Quantitative, Highly Accurate Evaluation of Cell-Free Circulating Tumor DNA

    PubMed Central

    Zill, Oliver A.; Sebisanovic, Dragan; Lopez, Rene; Blau, Sibel; Collisson, Eric A.; Divers, Stephen G.; Hoon, Dave S. B.; Kopetz, E. Scott; Lee, Jeeyun; Nikolinakos, Petros G.; Baca, Arthur M.; Kermani, Bahram G.; Eltoukhy, Helmy; Talasaz, AmirAli

    2015-01-01

    Next-generation sequencing of cell-free circulating solid tumor DNA addresses two challenges in contemporary cancer care. First this method of massively parallel and deep sequencing enables assessment of a comprehensive panel of genomic targets from a single sample, and second, it obviates the need for repeat invasive tissue biopsies. Digital SequencingTM is a novel method for high-quality sequencing of circulating tumor DNA simultaneously across a comprehensive panel of over 50 cancer-related genes with a simple blood test. Here we report the analytic and clinical validation of the gene panel. Analytic sensitivity down to 0.1% mutant allele fraction is demonstrated via serial dilution studies of known samples. Near-perfect analytic specificity (> 99.9999%) enables complete coverage of many genes without the false positives typically seen with traditional sequencing assays at mutant allele frequencies or fractions below 5%. We compared digital sequencing of plasma-derived cell-free DNA to tissue-based sequencing on 165 consecutive matched samples from five outside centers in patients with stage III-IV solid tumor cancers. Clinical sensitivity of plasma-derived NGS was 85.0%, comparable to 80.7% sensitivity for tissue. The assay success rate on 1,000 consecutive samples in clinical practice was 99.8%. Digital sequencing of plasma-derived DNA is indicated in advanced cancer patients to prevent repeated invasive biopsies when the initial biopsy is inadequate, unobtainable for genomic testing, or uninformative, or when the patient’s cancer has progressed despite treatment. Its clinical utility is derived from reduction in the costs, complications and delays associated with invasive tissue biopsies for genomic testing. PMID:26474073

  19. Analytical and Clinical Validation of a Digital Sequencing Panel for Quantitative, Highly Accurate Evaluation of Cell-Free Circulating Tumor DNA.

    PubMed

    Lanman, Richard B; Mortimer, Stefanie A; Zill, Oliver A; Sebisanovic, Dragan; Lopez, Rene; Blau, Sibel; Collisson, Eric A; Divers, Stephen G; Hoon, Dave S B; Kopetz, E Scott; Lee, Jeeyun; Nikolinakos, Petros G; Baca, Arthur M; Kermani, Bahram G; Eltoukhy, Helmy; Talasaz, AmirAli

    2015-01-01

    Next-generation sequencing of cell-free circulating solid tumor DNA addresses two challenges in contemporary cancer care. First this method of massively parallel and deep sequencing enables assessment of a comprehensive panel of genomic targets from a single sample, and second, it obviates the need for repeat invasive tissue biopsies. Digital Sequencing™ is a novel method for high-quality sequencing of circulating tumor DNA simultaneously across a comprehensive panel of over 50 cancer-related genes with a simple blood test. Here we report the analytic and clinical validation of the gene panel. Analytic sensitivity down to 0.1% mutant allele fraction is demonstrated via serial dilution studies of known samples. Near-perfect analytic specificity (> 99.9999%) enables complete coverage of many genes without the false positives typically seen with traditional sequencing assays at mutant allele frequencies or fractions below 5%. We compared digital sequencing of plasma-derived cell-free DNA to tissue-based sequencing on 165 consecutive matched samples from five outside centers in patients with stage III-IV solid tumor cancers. Clinical sensitivity of plasma-derived NGS was 85.0%, comparable to 80.7% sensitivity for tissue. The assay success rate on 1,000 consecutive samples in clinical practice was 99.8%. Digital sequencing of plasma-derived DNA is indicated in advanced cancer patients to prevent repeated invasive biopsies when the initial biopsy is inadequate, unobtainable for genomic testing, or uninformative, or when the patient's cancer has progressed despite treatment. Its clinical utility is derived from reduction in the costs, complications and delays associated with invasive tissue biopsies for genomic testing. PMID:26474073

  20. Feasibility of histogram analysis of susceptibility-weighted MRI for staging of liver fibrosis

    PubMed Central

    Yang, Zhao-Xia; Liang, He-Yue; Hu, Xin-Xing; Huang, Ya-Qin; Ding, Ying; Yang, Shan; Zeng, Meng-Su; Rao, Sheng-Xiang

    2016-01-01

    PURPOSE We aimed to evaluate whether histogram analysis of susceptibility-weighted imaging (SWI) could quantify liver fibrosis grade in patients with chronic liver disease (CLD). METHODS Fifty-three patients with CLD who underwent multi-echo SWI (TEs of 2.5, 5, and 10 ms) were included. Histogram analysis of SWI images were performed and mean, variance, skewness, kurtosis, and the 1st, 10th, 50th, 90th, and 99th percentiles were derived. Quantitative histogram parameters were compared. For significant parameters, further receiver operating characteristic (ROC) analyses were performed to evaluate the potential diagnostic performance for differentiating liver fibrosis stages. RESULTS The number of patients in each pathologic fibrosis grade was 7, 3, 5, 5, and 33 for F0, F1, F2, F3, and F4, respectively. The results of variance (TE: 10 ms), 90th percentile (TE: 10 ms), and 99th percentile (TE: 10 and 5 ms) in F0–F3 group were significantly lower than in F4 group, with areas under the ROC curves (AUCs) of 0.84 for variance and 0.70–0.73 for the 90th and 99th percentiles, respectively. The results of variance (TE: 10 and 5 ms), 99th percentile (TE: 10 ms), and skewness (TE: 2.5 and 5 ms) in F0–F2 group were smaller than those of F3/F4 group, with AUCs of 0.88 and 0.69 for variance (TE: 10 and 5 ms, respectively), 0.68 for 99th percentile (TE: 10 ms), and 0.73 and 0.68 for skewness (TE: 2.5 and 5 ms, respectively). CONCLUSION Magnetic resonance histogram analysis of SWI, particularly the variance, is promising for predicting advanced liver fibrosis and cirrhosis. PMID:27113421

  1. Experience with the MicroSeq D2 Large-Subunit Ribosomal DNA Sequencing Kit for Identification of Filamentous Fungi Encountered in the Clinical Laboratory

    PubMed Central

    Hall, Leslie; Wohlfiel, Sherri; Roberts, Glenn D.

    2004-01-01

    Described herein is our experience with the MicroSeq D2 large-subunit rDNA sequencing kit for the identification of filamentous fungi encountered in the mycology laboratory at the Mayo Clinic. A total of 234 filamentous fungi recovered from clinical specimens were used in the evaluation. All were identified by using phenotypic characteristics as observed macroscopically and microscopically on any medium or a combination of media, which included Sabouraud's dextrose, inhibitory mold, cornmeal, Czapek-Dox, potato dextrose, and V8 juice agars; all isolates were sequenced using the MicroSeq D2 large-subunit rDNA sequencing kit. Of the of 234 isolates, 158 were correctly identified to the appropriate genus or genus and species by using nucleic acid sequencing. Sequences for 70 (29.9%) of the isolates (27 genera) were not included in the MicroSeq library. Of the 80 dematiaceous and 154 hyaline fungi sequenced, 65 and 51.2%, respectively, gave results concordant with those determined by phenotypic identification. Nucleic acid sequencing using the MicroSeq D2 large-subunit rDNA sequencing kit offers promise of being an accurate identification system; however, the associated library needs to include more of the clinically important genera and species. PMID:14766826

  2. Analyzing Schizosaccharomyces pombe DNA Content by Flow Cytometry.

    PubMed

    Boye, Erik; Anda, Silje; Rothe, Christiane; Stokke, Trond; Grallert, Beáta

    2016-01-01

    Flow cytometry can be used to measure the DNA content of individual cells. The data are usually presented as DNA histograms that can be used to examine the cells' progression through the cell cycle. Under standard growth conditions, fission yeast cells do not complete cytokinesis until after G1 phase; therefore, DNA histograms show one major peak representing cells in G1 (2×1C DNA) and G2 phase (1×2C DNA). By analysis of the duration of the fluorescence signal as well as the intensity of the DNA-related signal, it is possible to discriminate between cells in M/G1, S, and G2 This protocol describes how to prepare cells for flow cytometry and analyze them. We also describe the application of barcoding for more accurate comparison of samples. PMID:27250946

  3. Digital image classification with the help of artificial neural network by simple histogram

    PubMed Central

    Dey, Pranab; Banerjee, Nirmalya; Kaur, Rajwant

    2016-01-01

    Background: Visual image classification is a great challenge to the cytopathologist in routine day-to-day work. Artificial neural network (ANN) may be helpful in this matter. Aims and Objectives: In this study, we have tried to classify digital images of malignant and benign cells in effusion cytology smear with the help of simple histogram data and ANN. Materials and Methods: A total of 404 digital images consisting of 168 benign cells and 236 malignant cells were selected for this study. The simple histogram data was extracted from these digital images and an ANN was constructed with the help of Neurointelligence software [Alyuda Neurointelligence 2.2 (577), Cupertino, California, USA]. The network architecture was 6-3-1. The images were classified as training set (281), validation set (63), and test set (60). The on-line backpropagation training algorithm was used for this study. Result: A total of 10,000 iterations were done to train the ANN system with the speed of 609.81/s. After the adequate training of this ANN model, the system was able to identify all 34 malignant cell images and 24 out of 26 benign cells. Conclusion: The ANN model can be used for the identification of the individual malignant cells with the help of simple histogram data. This study will be helpful in the future to identify malignant cells in unknown situations. PMID:27279679

  4. Statistical Analysis of Photopyroelectric Signals using Histogram and Kernel Density Estimation for differentiation of Maize Seeds

    NASA Astrophysics Data System (ADS)

    Rojas-Lima, J. E.; Domínguez-Pacheco, A.; Hernández-Aguilar, C.; Cruz-Orea, A.

    2016-09-01

    Considering the necessity of photothermal alternative approaches for characterizing nonhomogeneous materials like maize seeds, the objective of this research work was to analyze statistically the amplitude variations of photopyroelectric signals, by means of nonparametric techniques such as the histogram and the kernel density estimator, and the probability density function of the amplitude variations of two genotypes of maize seeds with different pigmentations and structural components: crystalline and floury. To determine if the probability density function had a known parametric form, the histogram was determined which did not present a known parametric form, so the kernel density estimator using the Gaussian kernel, with an efficiency of 95 % in density estimation, was used to obtain the probability density function. The results obtained indicated that maize seeds could be differentiated in terms of the statistical values for floury and crystalline seeds such as the mean (93.11, 159.21), variance (1.64× 103, 1.48× 103), and standard deviation (40.54, 38.47) obtained from the amplitude variations of photopyroelectric signals in the case of the histogram approach. For the case of the kernel density estimator, seeds can be differentiated in terms of kernel bandwidth or smoothing constant h of 9.85 and 6.09 for floury and crystalline seeds, respectively.

  5. Online Data Monitoring Framework Based on Histogram Packaging in Network Distributed Data Acquisition Systems

    NASA Astrophysics Data System (ADS)

    Konno, T.; Cabarera, A.; Ishitsuka, M.; Kuze, M.; Sakamoto, Y.

    2011-12-01

    "Online monitor framework" is a new general software framework for online data monitoring, which provides a way to collect information from online systems, including data acquisition, and displays them to shifters far from experimental sites. "Monitor Server", a core system in this framework gathers the monitoring information from the online subsystems and the information is handled as collections of histograms named "Histogram Package". Monitor Server broadcasts the histogram packages to "Monitor Viewers", graphical user interfaces in the framework. We developed two types of the viewers with different technologies: Java and web browser. We adapted XML based file for the configuration of GUI components on the windows and graphical objects on the canvases. Monitor Viewer creates its GUIs automatically with the configuration files.This monitoring framework has been developed for the Double Chooz reactor neutrino oscillation experiment in France, but can be extended for general application to be used in other experiments. This document reports the structure of the online monitor framework with some examples from the adaption to the Double Chooz experiment.

  6. Differentially Private Histogram Publication For Dynamic Datasets: An Adaptive Sampling Approach

    PubMed Central

    Li, Haoran; Jiang, Xiaoqian; Xiong, Li; Liu, Jinfei

    2016-01-01

    Differential privacy has recently become a de facto standard for private statistical data release. Many algorithms have been proposed to generate differentially private histograms or synthetic data. However, most of them focus on “one-time” release of a static dataset and do not adequately address the increasing need of releasing series of dynamic datasets in real time. A straightforward application of existing histogram methods on each snapshot of such dynamic datasets will incur high accumulated error due to the composibility of differential privacy and correlations or overlapping users between the snapshots. In this paper, we address the problem of releasing series of dynamic datasets in real time with differential privacy, using a novel adaptive distance-based sampling approach. Our first method, DSFT, uses a fixed distance threshold and releases a differentially private histogram only when the current snapshot is sufficiently different from the previous one, i.e., with a distance greater than a predefined threshold. Our second method, DSAT, further improves DSFT and uses a dynamic threshold adaptively adjusted by a feedback control mechanism to capture the data dynamics. Extensive experiments on real and synthetic datasets demonstrate that our approach achieves better utility than baseline methods and existing state-of-the-art methods. PMID:26973795

  7. A comparison of histogram distance metrics for content-based image retrieval

    NASA Astrophysics Data System (ADS)

    Zhang, Qianwen; Canosa, Roxanne L.

    2014-03-01

    The type of histogram distance metric selected for a CBIR query varies greatly and will affect the accuracy of the retrieval results. This paper compares the retrieval results of a variety of commonly used CBIR distance metrics: the Euclidean distance, the Manhattan distance, the vector cosine angle distance, histogram intersection distance, χ2 distance, Jensen-Shannon divergence, and the Earth Mover's distance. A training set of ground-truth labeled images is used to build a classifier for the CBIR system, where the images were obtained from three commonly used benchmarking datasets: the WANG dataset (http://savvash.blogspot.com/2008/12/benchmark-databases-for-cbir.html), the Corel Subset dataset (http://vision.stanford.edu/resources_links.html), and the CalTech dataset (http://www.vision.caltech.edu/htmlfiles/). To implement the CBIR system, we use the Tamura texture features of coarseness, contrast, and directionality. We create texture histograms of the training set and the query images, and then measure the difference between a randomly selected query and the corresponding retrieved image using a k-nearest-neighbors approach. Precision and recall is used to evaluate the retrieval performance of the system, given a particular distance metric. Then, given the same query image, the distance metric is changed and performance of the system is evaluated once again.

  8. Brightness preserving image enhancement based on a gradient and intensity histogram

    NASA Astrophysics Data System (ADS)

    Sun, Zebin; Feng, Wenquan; Zhao, Qi; Huang, Lidong

    2015-09-01

    We present a straightforward brightness preserving image enhancement technique. The proposed method is based on an original gradient and intensity histogram (GIH) which contains both gradient and intensity information of the image. This character enables GIH to avoid high peaks in the traditional intensity histogram and, thus alleviate overenhancement in our enhancement method, i.e., gradient and intensity histogram equalization (GIHE). GIHE can also enhance the gradient strength of an image, which is good for improving the subjective quality since the human vision system is more sensitive to the gradient than the absolute intensity of image. Considering that brightness preservation and dynamic range compression are highly demanded in consumer electronics, we manipulate the intensity of the enhanced image appropriately by amplifying the small intensities and attenuating the large intensities, respectively, using a brightness preserving function (BPF). The BPF is straightforward and universal and can be used in other image enhancement techniques. We demonstrate that the proposed method can effectively improve the subjective quality as well as preserve the brightness of the input image.

  9. LOR-OSEM: statistical PET reconstruction from raw line-of-response histograms

    PubMed Central

    Kadrmas, Dan J

    2010-01-01

    Iterative statistical reconstruction methods are becoming the standard in positron emission tomography (PET). Conventional maximum-likelihood expectation-maximization (MLEM) and ordered-subsets (OSEM) algorithms act on data which has been pre-processed into corrected, evenly-spaced histograms; however, such pre-processing corrupts the Poisson statistics. Recent advances have incorporated attenuation, scatter, and randoms compensation into the iterative reconstruction. The objective of this work was to incorporate the remaining preprocessing steps, including arc correction, to reconstruct directly from raw unevenly-spaced line-of-response (LOR) histograms. This exactly preserves Poisson statistics and full spatial information in a manner closely related to listmode ML, making full use of the ML statistical model. The LOR-OSEM algorithm was implemented using a rotation-based projector which maps directly to the unevenly-spaced LOR grid. Simulation and phantom experiments were performed to characterize resolution, contrast, and noise properties for 2D PET. LOR-OSEM provided a beneficial noise-resolution tradeoff, outperforming AW-OSEM by about the same margin that AW-OSEM outperformed pre-corrected OSEM. The relationship between LOR-ML and listmode ML algorithms was explored, and implementation differences are discussed. LOR-OSEM is a viable alternative to AW-OSEM for histogram-based reconstruction with improved spatial resolution and noise properties. PMID:15566171

  10. Flat-histogram Monte Carlo in the Classical Antiferromagnetic Ising Model

    NASA Astrophysics Data System (ADS)

    Brown, G.; Rikvold, P. A.; Nicholson, D. M.; Odbadrakh, Kh.; Yin, J.-Q.; Eisenbach, M.; Miyashita, S.

    2014-03-01

    Flat-histogram Monte Carlo methods, such as Wang-Landau and multicanonical sampling, are extremely useful in numerical studies of frustrated magnetic systems. Numerical tools such as windowing and discrete histograms introduce discontinuities along the continuous energy variable, which in turn introduce artifacts into the calculated density of states. We demonstrate these effects and introduce practical solutions, including ``guard regions'' with biased walks for windowing and analytic representations for histograms. The classical Ising antiferromagnet supplemented by a mean-field interaction is considered. In zero field, the allowed energies are discrete and the artifacts can be avoided in small systems by not binning. For large systems, or cases where non-zero fields are used to break the degeneracy between local energy minima, the energy becomes continuous and these artifacts must be taken into account. Work performed at ORNL, managed by UT-Batelle for the US DOE; sponsored by Div of Mat Sci & Eng, Office of BES; used resources of Oak Ridge Leadership Computing Facility at ORNL, supported by Office of Science Contract DE-AC05-00OR22725.

  11. Compensating Acoustic Mismatch Using Class-Based Histogram Equalization for Robust Speech Recognition

    NASA Astrophysics Data System (ADS)

    Suh, Youngjoo; Kim, Sungtak; Kim, Hoirin

    2007-12-01

    A new class-based histogram equalization method is proposed for robust speech recognition. The proposed method aims at not only compensating for an acoustic mismatch between training and test environments but also reducing the two fundamental limitations of the conventional histogram equalization method, the discrepancy between the phonetic distributions of training and test speech data, and the nonmonotonic transformation caused by the acoustic mismatch. The algorithm employs multiple class-specific reference and test cumulative distribution functions, classifies noisy test features into their corresponding classes, and equalizes the features by using their corresponding class reference and test distributions. The minimum mean-square error log-spectral amplitude (MMSE-LSA)-based speech enhancement is added just prior to the baseline feature extraction to reduce the corruption by additive noise. The experiments on the Aurora2 database proved the effectiveness of the proposed method by reducing relative errors by[InlineEquation not available: see fulltext.] over the mel-cepstral-based features and by[InlineEquation not available: see fulltext.] over the conventional histogram equalization method, respectively.

  12. [DNA aneuploidy in children with acute leukemia: II. Correlation with the phenotype of blasts, clinical picture and course of disease].

    PubMed

    Ritter, J; Hiddemann, W; Wörmann, B; Büchner, T; Schellong, G

    1985-01-01

    Analysis of the cellular DNA content was carried out in 162 children with ALL and 34 children with AML admitted to the university children's hospital Münster between 1979 and 1984. DNA aneuploidies were identified at a similar frequency in ALL (40%) and AML (44%). However, the degree of DNA aneuploidies (DNA-index) was significantly lower in aneuploid AML (median 1.09) than in aneuploid ALL (median 1.19). We found a significantly lower incidence of DNA-aneuploidies in T-ALL (3/21; 14%) as compared to non-T/non-B-ALL (60/137; 44%). No differences were found between children with and without DNA aneuploidy in PAS score and TdT activity. In non-T/non-B-ALL DNA aneuploidy is highly correlated with a long pretherapeutic history, with a low WBC and blast count and with a low serum LDH. Under the conditions of the ALL protocols BFM-79/81 and 81/83 no difference in the remission rate was found between the two patient groups. However, more relapses occurred so far within the group of children without DNS aneuploidy. PMID:3892150

  13. Measuring kinetics of complex single ion channel data using mean-variance histograms.

    PubMed Central

    Patlak, J B

    1993-01-01

    The measurement of single ion channel kinetics is difficult when those channels exhibit subconductance events. When the kinetics are fast, and when the current magnitudes are small, as is the case for Na+, Ca2+, and some K+ channels, these difficulties can lead to serious errors in the estimation of channel kinetics. I present here a method, based on the construction and analysis of mean-variance histograms, that can overcome these problems. A mean-variance histogram is constructed by calculating the mean current and the current variance within a brief "window" (a set of N consecutive data samples) superimposed on the digitized raw channel data. Systematic movement of this window over the data produces large numbers of mean-variance pairs which can be assembled into a two-dimensional histogram. Defined current levels (open, closed, or sublevel) appear in such plots as low variance regions. The total number of events in such low variance regions is estimated by curve fitting and plotted as a function of window width. This function decreases with the same time constants as the original dwell time probability distribution for each of the regions. The method can therefore be used: 1) to present a qualitative summary of the single channel data from which the signal-to-noise ratio, open channel noise, steadiness of the baseline, and number of conductance levels can be quickly determined; 2) to quantify the dwell time distribution in each of the levels exhibited. In this paper I present the analysis of a Na+ channel recording that had a number of complexities. The signal-to-noise ratio was only about 8 for the main open state, open channel noise, and fast flickers to other states were present, as were a substantial number of subconductance states. "Standard" half-amplitude threshold analysis of these data produce open and closed time histograms that were well fitted by the sum of two exponentials, but with apparently erroneous time constants, whereas the mean

  14. Enhancing tumor apparent diffusion coefficient histogram skewness stratifies the postoperative survival in recurrent glioblastoma multiforme patients undergoing salvage surgery.

    PubMed

    Zolal, Amir; Juratli, Tareq A; Linn, Jennifer; Podlesek, Dino; Sitoci Ficici, Kerim Hakan; Kitzler, Hagen H; Schackert, Gabriele; Sobottka, Stephan B; Rieger, Bernhard; Krex, Dietmar

    2016-05-01

    Objective To determine the value of apparent diffusion coefficient (ADC) histogram parameters for the prediction of individual survival in patients undergoing surgery for recurrent glioblastoma (GBM) in a retrospective cohort study. Methods Thirty-one patients who underwent surgery for first recurrence of a known GBM between 2008 and 2012 were included. The following parameters were collected: age, sex, enhancing tumor size, mean ADC, median ADC, ADC skewness, ADC kurtosis and fifth percentile of the ADC histogram, initial progression free survival (PFS), extent of second resection and further adjuvant treatment. The association of these parameters with survival and PFS after second surgery was analyzed using log-rank test and Cox regression. Results Using log-rank test, ADC histogram skewness of the enhancing tumor was significantly associated with both survival (p = 0.001) and PFS after second surgery (p = 0.005). Further parameters associated with prolonged survival after second surgery were: gross total resection at second surgery (p = 0.026), tumor size (0.040) and third surgery (p = 0.003). In the multivariate Cox analysis, ADC histogram skewness was shown to be an independent prognostic factor for survival after second surgery. Conclusion ADC histogram skewness of the enhancing lesion, enhancing lesion size, third surgery, as well as gross total resection have been shown to be associated with survival following the second surgery. ADC histogram skewness was an independent prognostic factor for survival in the multivariate analysis. PMID:26830088

  15. Association of 5-methylcytosine and 5-hydroxymethylcytosine with mitochondrial DNA content and clinical and biochemical parameters in hepatocellular carcinoma.

    PubMed

    Shen, Fan; Huang, Wei; Qi, Jia-Hui; Yuan, Bi-Feng; Huang, Jing-Tao; Zhou, Xin; Feng, Yu-Qi; Liu, Ying-Juan; Liu, Song-Mei

    2013-01-01

    Increasing epidemiological evidence has indicated that inherited variations of mitochondrial DNA (mtDNA) copy number affect the genetic susceptibility of many malignancies in a tumour-specific manner and that DNA methylation also plays an important role in controlling gene expression during the differentiation and development of hepatocellular carcinoma (HCC). Our previous study demonstrated that HCC tissues showed a lower 5-hydroxymethylcytosine (5-hmC) content when compared to tumour-adjacent tissues, but the relationship among 5-hmC, 5-methylcytosine (5-mC) and mtDNA content in HCC patients is still unknown. This study aimed to clarify the correlation among mtDNA content, 5-mC and 5-hmC by quantitative real-time PCR and liquid chromatography tandem mass spectrometry analysis. We demonstrated that 5-hmC correlated with tumour size [odds ratio (OR) 0.847, 95% confidence interval (CI) 0.746-0.962, P = 0.011], and HCC patients with a tumour size ≥ 5.0 cm showed a lower 5-hmC content and higher levels of fasting plasma aspartate aminotransferase, the ratio of alanine aminotransferase to aspartate aminotransferase, γ-glutamyltransferase, alpha-fetoprotein than those with a tumour size <5 cm (all P<0.05). We further revealed that the mtDNA content of HCC tumour tissues was 225.97(105.42, 430.54) [median (25th Percentile, 75th Percentile)] and was negatively correlated with 5-mC content (P = 0.035), but not 5-hmC content, in genomic DNA from HCC tumour tissues. PMID:24143196

  16. Clinical profile of hearing loss in children with congenital cytomegalovirus (CMV) infection: CMV DNA diagnosis using preserved umbilical cord

    PubMed Central

    2011-01-01

    Conclusions: Congenital cytomegalovirus (CMV) infection is a major cause of bilateral and unilateral sensorineural hearing loss (SNHL) in children, accounting for 9.0% of SNHL cases. The diagnostic rate using combined genetic deafness test and CMV DNA detection test was determined to be 46.4% in bilateral profound SNHL. Objectives. The present study investigated the prevalence of congenital CMV infection diagnosed retrospectively by detection of CMV DNA in dried umbilical cord specimens from children with unilateral or bilateral SNHL up to the age of 12 years. Methods: Preserved dried umbilical cords were collected from 134 children with bilateral (46 children) or unilateral (88 children) SNHL. DNA was extracted from the dried umbilical cords and CMV DNA was detected by quantitative PCR. Genetic deafness tests based on the invader assay were performed in children with bilateral SNHL. Results: CMV DNA from the dried umbilical cords was detected in 8.7% of the bilateral SNHL and 9.1% of unilateral SNHL. Deafness gene mutations were identified in 21.7% (10/46) of children with bilateral SNHL. PMID:21612560

  17. Validation and clinical application of a molecular method for the identification of Cryptococcus neoformans/Cryptococcus gattii complex DNA in human clinical specimens.

    PubMed

    Rivera, Vanessa; Gaviria, Marcela; Muñoz-Cadavid, Cesar; Cano, Luz; Naranjo, Tonny

    2015-01-01

    The diagnosis of cryptococcosis is usually performed based on cultures of tissue or body fluids and isolation of the fungus, but this method may require several days. Direct microscopic examination, although rapid, is relatively insensitive. Biochemical and immunodiagnostic rapid tests are also used. However, all of these methods have limitations that may hinder final diagnosis. The increasing incidence of fungal infections has focused attention on tools for rapid and accurate diagnosis using molecular biological techniques. Currently, PCR-based methods, particularly nested, multiplex and real-time PCR, provide both high sensitivity and specificity. In the present study, we evaluated a nested PCR targeting the gene encoding the ITS-1 and ITS-2 regions of rDNA in samples from a cohort of patients diagnosed with cryptococcosis. The results showed that in our hands, this Cryptococcus nested PCR assay has 100% specificity and 100% sensitivity and was able to detect until 2 femtograms of Cryptococcus DNA. PMID:26365230

  18. Partial-volume Bayesian classification of material mixtures in MR volume data using voxel histograms.

    PubMed

    Laidlaw, D H; Fleischer, K W; Barr, A H

    1998-02-01

    We present a new algorithm for identifying the distribution of different material types in volumetric datasets such as those produced with magnetic resonance imaging (MRI) or computed tomography (CT). Because we allow for mixtures of materials and treat voxels as regions, our technique reduces errors that other classification techniques can create along boundaries between materials and is particularly useful for creating accurate geometric models and renderings from volume data. It also has the potential to make volume measurements more accurately and classifies noisy, low-resolution data well. There are two unusual aspects to our approach. First, we assume that, due to partial-volume effects, or blurring, voxels can contain more than one material, e.g., both muscle and fat; we compute the relative proportion of each material in the voxels. Second, we incorporate information from neighboring voxels into the classification process by reconstructing a continuous function, rho(x), from the samples and then looking at the distribution of values that rho(x) takes on within the region of a voxel. This distribution of values is represented by a histogram taken over the region of the voxel; the mixture of materials that those values measure is identified within the voxel using a probabilistic Bayesian approach that matches the histogram by finding the mixture of materials within each voxel most likely to have created the histogram. The size of regions that we classify is chosen to match the spacing of the samples because the spacing is intrinsically related to the minimum feature size that the reconstructed continuous function can represent. PMID:9617909

  19. A Novel Method for the Evaluation of Uncertainty in Dose-Volume Histogram Computation

    SciTech Connect

    Henriquez, Francisco Cutanda M.Sc. Castrillon, Silvia Vargas

    2008-03-15

    Purpose: Dose-volume histograms (DVHs) are a useful tool in state-of-the-art radiotherapy treatment planning, and it is essential to recognize their limitations. Even after a specific dose-calculation model is optimized, dose distributions computed by using treatment-planning systems are affected by several sources of uncertainty, such as algorithm limitations, measurement uncertainty in the data used to model the beam, and residual differences between measured and computed dose. This report presents a novel method to take them into account. Methods and Materials: To take into account the effect of associated uncertainties, a probabilistic approach using a new kind of histogram, a dose-expected volume histogram, is introduced. The expected value of the volume in the region of interest receiving an absorbed dose equal to or greater than a certain value is found by using the probability distribution of the dose at each point. A rectangular probability distribution is assumed for this point dose, and a formulation that accounts for uncertainties associated with point dose is presented for practical computations. Results: This method is applied to a set of DVHs for different regions of interest, including 6 brain patients, 8 lung patients, 8 pelvis patients, and 6 prostate patients planned for intensity-modulated radiation therapy. Conclusions: Results show a greater effect on planning target volume coverage than in organs at risk. In cases of steep DVH gradients, such as planning target volumes, this new method shows the largest differences with the corresponding DVH; thus, the effect of the uncertainty is larger.

  20. Optimized swimmer tracking system by a dynamic fusion of correlation and color histogram techniques

    NASA Astrophysics Data System (ADS)

    Benarab, D.; Napoléon, T.; Alfalou, A.; Verney, A.; Hellard, P.

    2015-12-01

    To design a robust swimmer tracking system, we took into account two well-known tracking techniques: the nonlinear joint transform correlation (NL-JTC) and the color histogram. The two techniques perform comparably well, yet they both have substantial limitations. Interestingly, they also seem to show some complementarity. The correlation technique yields accurate detection but is sensitive to rotation, scale and contour deformation, whereas the color histogram technique is robust for rotation and contour deformation but shows low accuracy and is highly sensitive to luminosity and confusing background colors. These observations suggested the possibility of a dynamic fusion of the correlation plane and the color scores map. Before this fusion, two steps are required. First is the extraction of a sub-plane of correlation that describes the similarity between the reference and target images. This sub-plane has the same size as the color scores map but they have different interval values. Thus, the second step is required which is the normalization of the planes in the same interval so they can be fused. In order to determine the benefits of this fusion technique, first, we tested it on a synthetic image containing different forms with different colors. We thus were able to optimize the correlation plane and color histogram techniques before applying our fusion technique to real videos of swimmers in international competitions. Last, a comparative study of the dynamic fusion technique and the two classical techniques was carried out to demonstrate the efficacy of the proposed technique. The criteria of comparison were the tracking percentage, the peak to correlation energy (PCE), which evaluated the sharpness of the peak (accuracy), and the local standard deviation (Local-STD), which assessed the noise in the planes (robustness).

  1. A microfluidic electrochemical biosensor based on multiwall carbon nanotube/ferrocene for genomic DNA detection of Mycobacterium tuberculosis in clinical isolates.

    PubMed

    Zribi, B; Roy, E; Pallandre, A; Chebil, S; Koubaa, M; Mejri, N; Magdinier Gomez, H; Sola, C; Korri-Youssoufi, H; Haghiri-Gosnet, A-M

    2016-01-01

    Herein we present a microfluidic-multiplexed platform that integrates electrochemical sensors based on carbon nanotubes associated with ferrocene as redox marker (carbon nanotube (CNT)/ferrocene) for direct detection of pathogenic viral DNA from Hepatitis C and genomic DNA from Mycobacterium tuberculosis in clinical isolates. By operating the fluidic device under high flow (150 μl/min), the formation of a very thin depletion layer at the sensor surface (δS = 230 nm) enhances the capture rate up to one DNA strand per second. By comparison, this capture rate is only 0.02 molecule/s in a static regime without flow. This fluidic protocol allows thus enhancing the limit of detection of the electrochemical biosensor from picomolar in bulk solution to femtomolar with a large dynamic range from 0.1 fM to 1 pM. Kinetics analysis also demonstrates an enhancement of the rate constant of electron transfer (kS) of the electrochemical process from 1 s(-1) up to 6 s(-1) thanks to the geometry of the miniaturized fluidic electrochemical cell. This microfluidic device working under high flow allows selective direct detection of a Mycobacterium tuberculosis (H37Rv) rpoB allele from clinical isolate extracted DNA. We envision that a microfluidic approach under high flow associated with a multiwall CNT/ferrocene sensor could find useful applications as the point-of-care for multi-target diagnostics of biomarkers in real samples. PMID:26865908

  2. Numerical study of QCD phase diagram at high temperature and density by a histogram method

    NASA Astrophysics Data System (ADS)

    Ejiri, Shinji; Aoki, Sinya; Hatsuda, Tetsuo; Kanaya, Kazuyuki; Nakagawa, Yoshiyuki; Ohno, Hiroshi; Saito, Hana; Umeda, Takashi

    2012-12-01

    We study the QCD phase structure at high temperature and density adopting a histogram method. Because the quark determinant is complex at finite density, the Monte-Carlo method cannot be applied directly. We use a reweighting method and try to solve the problems which arise in the reweighting method, i.e. the sign problem and the overlap problem. We discuss the chemical potential dependence of the probability distribution function in the heavy quark mass region and examine the applicability of the approach in the light quark region.

  3. Phase-unwrapping algorithm for images with high noise content based on a local histogram

    NASA Astrophysics Data System (ADS)

    Meneses, Jaime; Gharbi, Tijani; Humbert, Philippe

    2005-03-01

    We present a robust algorithm of phase unwrapping that was designed for use on phase images with high noise content. We proceed with the algorithm by first identifying regions with continuous phase values placed between fringe boundaries in an image and then phase shifting the regions with respect to one another by multiples of 2pi to unwrap the phase. Image pixels are segmented between interfringe and fringe boundary areas by use of a local histogram of a wrapped phase. The algorithm has been used successfully to unwrap phase images generated in a three-dimensional shape measurement for noninvasive quantification of human skin structure in dermatology, cosmetology, and plastic surgery.

  4. Segmentation of neuronal-cell images from stained fields and monomodal histograms.

    PubMed

    Pham, Tuan D; Crane, Denis I

    2005-01-01

    Information from images taken of cells being grown in culture with oxidative agents allows life science researchers to compare changes in neurons from the Zellweger mice to those from normal mice. Image segmentation is the major and first step for the study of these different types of processes in cells. In this paper we develop an innovative strategy for the segmentation of neuronal-cell images which are subjected to stains and whose histograms are monomodal. Such nontrival images make it a challenging task for many existing image segmentation methods. We show that the proposed method is an effective and simple procedure for the subsequent quantitative analysis of neuronal images. PMID:17281705

  5. Early detection of Alzheimer's disease using histograms in a dissimilarity-based classification framework

    NASA Astrophysics Data System (ADS)

    Luchtenberg, Anne; Simões, Rita; van Cappellen van Walsum, Anne-Marie; Slump, Cornelis H.

    2014-03-01

    Classification methods have been proposed to detect early-stage Alzheimer's disease using Magnetic Resonance images. In particular, dissimilarity-based classification has been applied using a deformation-based distance measure. However, such approach is not only computationally expensive but it also considers large-scale alterations in the brain only. In this work, we propose the use of image histogram distance measures, determined both globally and locally, to detect very mild to mild Alzheimer's disease. Using an ensemble of local patches over the entire brain, we obtain an accuracy of 84% (sensitivity 80% and specificity 88%).

  6. Retinal vessel enhancement based on multi-scale top-hat transformation and histogram fitting stretching

    NASA Astrophysics Data System (ADS)

    Liao, Miao; Zhao, Yu-qian; Wang, Xiao-hong; Dai, Pei-shan

    2014-06-01

    Retinal vessels play an important role in the diagnostic procedure of retinopathy. A new retinal vessel enhancement method is proposed in this paper. Firstly, the optimal bright and dim image features of an original retinal image are extracted by a multi-scale top-hat transformation. Then, the retinal image is enhanced preliminarily by adding the optimal bright image features and removing the optimal dim image features. Finally, the preliminarily enhanced image is further processed by linear stretching with histogram Gaussian curve fitting. The experiments results on the DRIVE and STARE databases show that the proposed method improves the contrast and enhances the details of the retinal vessels effectively.

  7. Verification of dose volume histograms in stereotactic radiosurgery and radiotherapy using polymer gel and MRI

    NASA Astrophysics Data System (ADS)

    Šemnická, Jitka; Novotný, Josef, Jr.; Spěváček, Václav; Garčic, Jirí; Steiner, Martin; Judas, Libor

    2006-12-01

    In this work we focus on dose volume histograms (DVHs) measurement in stereotactic radiosurgery (SR) performed with the Leksell gamma knife (ELEKTA Instrument AB, Stockholm, Sweden) and stereotactic radiotherapy (SRT) performed with linear accelerator 6 MV Varian Clinac 2100 C/D (Varian Medical Systems, Palo Alto, USA) in conjunction with BrainLAB stereotactic system (BrainLAB, Germany) using modified BANG gel and magnetic resonance imaging (MRI). The aim of the experiments was to investigate a method for acquiring entire dose volume information from irradiated gel dosimeter and calculate DVHs.

  8. Dose-Volume Histogram Analysis of Stereotactic Body Radiotherapy Treatment of Pancreatic Cancer: A Focus on Duodenal Dose Constraints.

    PubMed

    Goldsmith, Christy; Price, Patricia; Cross, Timothy; Loughlin, Sheila; Cowley, Ian; Plowman, Nicholas

    2016-04-01

    Pancreatic carcinoma is an aggressive disease and radiotherapy treatment delivery to the primary tumor is constrained by the anatomical close location of the duodenum, stomach, and small bowel. Duodenal dose tolerance for radiosurgery in 2-5 fractions has been largely unknown. The literature was surveyed for quantitative models of risk in 1-5 fractions and we analyzed our own patient population of 44 patients with unresectable pancreatic tumors who received 3 or 5 fractions of stereotactic body radiotherapy (SBRT) between March 2009 and March 2013. A logistic model was constructed in the dose-volume histogram (DVH) Evaluator software for the duodenal D50%, D30cc, D5cc, D1cc, and maximum point dose D0.035cc. Dose tolerance limits from the literature were overlaid onto the clinical duodenal data in the form of a DVH Risk Map, with risk levels of the published limits estimated from the model of clinical data. In 3 fractions, Kopek 2010 found a statistically significant difference in D1cc of patients with no common terminology criteria for adverse events (CTCAE) v3 grade 2 or higher duodenal complications (mean D1cc = 25.3Gy) as compared with patients with grade 2 or higher toxicity (mean D1cc = 37.4Gy). From the logistic model of our duodenal data in 3 fractions, D1cc = 25.3Gy had 4.7% risk of grade 3-4 hemorrhage or stricture and D1cc = 37.4Gy had 20% risk. The 10% risk level was D1cc = 31.4Gy and we were able to keep duodenum dose for all our patients later this level. PMID:27000512

  9. Evaluation of the MicroSeq System for Identification of Mycobacteria by 16S Ribosomal DNA Sequencing and Its Integration into a Routine Clinical Mycobacteriology Laboratory

    PubMed Central

    Hall, Leslie; Doerr, Kelly A.; Wohlfiel, Sherri L.; Roberts, Glenn D.

    2003-01-01

    An evaluation of the MicroSeq 500 microbial identification system by nucleic acid sequencing and the Mayo Clinic experience with its integration into a routine clinical laboratory setting are described. Evaluation of the MicroSeq 500 microbial identification system was accomplished with 59 American Type Culture Collection (ATCC) strains and 328 clinical isolates of mycobacteria identified by conventional and 16S ribosomal DNA sequencing by using the MicroSeq 500 microbial identification system. Nucleic acid sequencing identified 58 of 59 (98.3%) ATCC strains to the species level or to the correct group or complex level. The identification results for 219 of 243 clinical isolates (90.1%) with a distance score of <1% were concordant with the identifications made by phenotypic methods. The remaining 85 isolates had distance scores of >1%; 35 (41.1%) were identified to the appropriate species level or group or complex level; 13 (15.3%) were identified to the species level. All 85 isolates were determined to be mycobacterial species, either novel species or species that exhibited significant genotypic divergence from an organism in the database with the closest match. Integration of nucleic acid sequencing into the routine mycobacteriology laboratory and use of the MicroSeq 500 microbial identification system and Mayo Clinic databases containing additional genotypes of common species and added species significantly reduced the number of organisms that could not be identified by phenotypic methods. The turnaround time was shortened to 24 h, and results were reported much earlier. A limited number of species could not be differentiated from one another by 16S ribosomal DNA sequencing; however, the method provides for the identification of unusual species and more accurate identifications and offers the promise of being the most accurate method available. PMID:12682128

  10. PCR assay based on DNA coding for 16S rRNA for detection and identification of mycobacteria in clinical samples.

    PubMed Central

    Kox, L F; van Leeuwen, J; Knijper, S; Jansen, H M; Kolk, A H

    1995-01-01

    A PCR and a reverse cross blot hybridization assay were developed for the detection and identification of mycobacteria in clinical samples. The PCR amplifies a part of the DNA coding for 16S rRNA with a set of primers that is specific for the genus Mycobacterium and that flanks species-specific sequences within the genes coding for 16S rRNA. The PCR product is analyzed in a reverse cross blot hybridization assay with probes specific for M. tuberculosis complex (pTub1), M. avium (pAvi3), M. intracellulare (pInt5 and pInt7), M. kansasii complex-M. scrofulaceum complex (pKan1), M. xenopi (pXen1), M. fortuitum (pFor1), M. smegmatis (pSme1), and Mycobacterium spp. (pMyc5a). The PCR assay can detect 10 fg of DNA, the equivalent of two mycobacteria. The specificities of the probes were tested with 108 mycobacterial strains (33 species) and 31 nonmycobacterial strains (of 17 genera). The probes pAvi3, pInt5, pInt7, pKan1, pXen1, and pMyc5a were specific. With probes pTub1, pFor1, and pSme1, slight cross hybridization occurred. However, the mycobacterial strains from which the cross-hybridizing PCR products were derived belonged to nonpathogenic or nonopportunistic species which do not occur in clinical samples. The test was used on 31 different clinical specimens obtained from patients suspected of having mycobacterial disease, including a patient with a double mycobacterial infection. The samples included sputum, bronchoalveolar lavage, tissue biopsy samples, cerebrospinal fluid, pus, peritoneal fluid, pleural fluid, and blood. The results of the PCR assay agreed with those of conventional identification methods or with clinical data, showing that the test can be used for the direct and rapid detection and identification of mycobacteria in clinical samples. PMID:8586707

  11. A comprehensive investigation of sperm DNA damage and oxidative stress injury in infertile patients with subclinical, normozoospermic, and astheno/oligozoospermic clinical varicocoele.

    PubMed

    Ni, K; Steger, K; Yang, H; Wang, H; Hu, K; Zhang, T; Chen, B

    2016-09-01

    One of the main pathogeneses of varicocoele and infertility is oxidative stress (OS), nevertheless, the oxidative damaged DNA in infertile patients with varicocoele remains poorly clarified. The objective of this study was to comprehensively investigate whether sperm DNA damage and OS injury were related with different issues of varicocoele. According to the varicocoele practice guidelines, surgical treatment was not indicated in the infertile patients with subclinical (SubVc, n = 15) and normozoospermic clinical varicocoele (NCVc, n = 22), the infertile astheno/oligozoospermic patients with clinical varicocoele (AOCVc, n = 51) would receive microsurgerical varicocoelectomy. Normozoospermic healthy donors with proven fertility (n = 25) were recruited as controls. Thiobarbituric acid and sperm chromatin structure assay (SCSA) methods were preformed to analyze seminal lipid peroxidation product malondialdehyde (MDA) and sperm DNA fragmentation index (DFI). We found that AOCVc and NCVc, except SubVc, could significantly elevate sperm DFI and seminal MDA levels. Varicocoelectomy could substantially improve semen parameters, and reduce sperm DFI and seminal MDA levels in the AOCVc patients. However, the non-operative NCVc patients would possibly suffer a severe deterioration of semen parameters accompanied by aberrantly higher levels of sperm DFI and seminal MDA, whereas no differences occurred in the non-operative SubVc patients. Sperm DFI level in the pregnant group was much lower compared to the non-pregnant group (AOCVc, p < 0.01; NCVc, p < 0.05) with the best cutoff value of 19.73%, while no differences in seminal MDA (p > 0.05) could be observed. Finally, a strong positive correlation was found between sperm DFI and seminal MDA (Rs = 0.504, p < 0.01), and they were also closely correlated with crucial semen parameters except normal morphology. Therefore, sperm DNA damage in clinical varicocoele, but not in SubVc, might be associated with the role

  12. Automatic histogram-based segmentation of white matter hyperintensities using 3D FLAIR images

    NASA Astrophysics Data System (ADS)

    Simões, Rita; Slump, Cornelis; Moenninghoff, Christoph; Wanke, Isabel; Dlugaj, Martha; Weimar, Christian

    2012-03-01

    White matter hyperintensities are known to play a role in the cognitive decline experienced by patients suffering from neurological diseases. Therefore, accurately detecting and monitoring these lesions is of importance. Automatic methods for segmenting white matter lesions typically use multimodal MRI data. Furthermore, many methods use a training set to perform a classification task or to determine necessary parameters. In this work, we describe and evaluate an unsupervised segmentation method that is based solely on the histogram of FLAIR images. It approximates the histogram by a mixture of three Gaussians in order to find an appropriate threshold for white matter hyperintensities. We use a context-sensitive Expectation-Maximization method to determine the Gaussian mixture parameters. The segmentation is subsequently corrected for false positives using the knowledge of the location of typical FLAIR artifacts. A preliminary validation with the ground truth on 6 patients revealed a Similarity Index of 0.73 +/- 0.10, indicating that the method is comparable to others in the literature which require multimodal MRI and/or a preliminary training step.

  13. Free energies from dynamic weighted histogram analysis using unbiased Markov state model.

    PubMed

    Rosta, Edina; Hummer, Gerhard

    2015-01-13

    The weighted histogram analysis method (WHAM) is widely used to obtain accurate free energies from biased molecular simulations. However, WHAM free energies can exhibit significant errors if some of the biasing windows are not fully equilibrated. To account for the lack of full equilibration, we develop the dynamic histogram analysis method (DHAM). DHAM uses a global Markov state model to obtain the free energy along the reaction coordinate. A maximum likelihood estimate of the Markov transition matrix is constructed by joint unbiasing of the transition counts from multiple umbrella-sampling simulations along discretized reaction coordinates. The free energy profile is the stationary distribution of the resulting Markov matrix. For this matrix, we derive an explicit approximation that does not require the usual iterative solution of WHAM. We apply DHAM to model systems, a chemical reaction in water treated using quantum-mechanics/molecular-mechanics (QM/MM) simulations, and the Na(+) ion passage through the membrane-embedded ion channel GLIC. We find that DHAM gives accurate free energies even in cases where WHAM fails. In addition, DHAM provides kinetic information, which we here use to assess the extent of convergence in each of the simulation windows. DHAM may also prove useful in the construction of Markov state models from biased simulations in phase-space regions with otherwise low population. PMID:26574225

  14. Two non-parametric methods for derivation of constraints from radiotherapy dose-histogram data

    NASA Astrophysics Data System (ADS)

    Ebert, M. A.; Gulliford, S. L.; Buettner, F.; Foo, K.; Haworth, A.; Kennedy, A.; Joseph, D. J.; Denham, J. W.

    2014-07-01

    Dose constraints based on histograms provide a convenient and widely-used method for informing and guiding radiotherapy treatment planning. Methods of derivation of such constraints are often poorly described. Two non-parametric methods for derivation of constraints are described and investigated in the context of determination of dose-specific cut-points—values of the free parameter (e.g., percentage volume of the irradiated organ) which best reflect resulting changes in complication incidence. A method based on receiver operating characteristic (ROC) analysis and one based on a maximally-selected standardized rank sum are described and compared using rectal toxicity data from a prostate radiotherapy trial. Multiple test corrections are applied using a free step-down resampling algorithm, which accounts for the large number of tests undertaken to search for optimal cut-points and the inherent correlation between dose-histogram points. Both methods provide consistent significant cut-point values, with the rank sum method displaying some sensitivity to the underlying data. The ROC method is simple to implement and can utilize a complication atlas, though an advantage of the rank sum method is the ability to incorporate all complication grades without the need for grade dichotomization.

  15. Particle swarm optimized multi-objective histogram equalization for image enhancement

    NASA Astrophysics Data System (ADS)

    Shanmugavadivu, P.; Balasubramanian, K.

    2014-04-01

    Histogram Equalization (HE) is a simple and effective technique for enhancing the contrast of the input image. However, it fails to preserve the brightness while enhancing the contrast due to the abrupt mean shift during the process of equalization. Many HE based methods have been developed to overcome the problem of mean shift. But, they suffered from over-enhancement. In this paper, a multi-objective HE model has been proposed in order to enhance the contrast as well as to preserve the brightness. The central idea of this technique is to first segment the histogram of the input image into two using Otsu's threshold. A set of optimized weighing constraints are formulated and applied on both the sub-images. Then, the sub-images are equalized independently and their union produces the contrast enhanced, brightness preserved output image. Here, Particle Swarm Optimization (PSO) is employed to find the optimal constraints. This technique is proved to have an edge over the other contemporary methods in terms of entropy and contrast improvement index.

  16. Infrared image enhancement based on atmospheric scattering model and histogram equalization

    NASA Astrophysics Data System (ADS)

    Li, Yi; Zhang, Yunfeng; Geng, Aihui; Cao, Lihua; Chen, Juan

    2016-09-01

    Infrared images are fuzzy due to the special imaging technology of infrared sensor. In order to achieve contrast enhancement and gain clear edge details from a fuzzy infrared image, we propose an efficient enhancement method based on atmospheric scattering model and histogram equalization. The novel algorithm optimizes and improves the visual image haze remove method which combines the characteristics of the fuzzy infrared images. Firstly, an average filtering operation is presented to get the estimation of coarse transmission rate. Then we get the fuzzy free image through self-adaptive transmission rate calculated with the statistics information of original infrared image. Finally, to deal with low lighting problem of fuzzy free image, we propose a sectional plateau histogram equalization method which is capable of background suppression. Experimental results show that the performance and efficiency of the proposed algorithm are pleased, compared to four other algorithms in both subjective observation and objective quantitative evaluation. In addition, the proposed algorithm is competent to enhance infrared image for different applications under different circumstances.

  17. Validation of Vehicle Candidate Areas in Aerial Images Using Color Co-Occurrence Histograms

    NASA Astrophysics Data System (ADS)

    Leister, W.; Tuermer, S.; Reinartz, P.; Hoffmann, K. H.; Stilla, U.

    2013-10-01

    Traffic monitoring plays an important role in transportation management. In addition, airborne acquisition enables a flexible and realtime mapping for special traffic situations e.g. mass events and disasters. Also the automatic extraction of vehicles from aerial imagery is a common application. However, many approaches focus on the target object only. As an extension to previously developed car detection techniques, a validation scheme is presented. The focus is on exploiting the background of the vehicle candidates as well as their color properties in the HSV color space. Therefore, texture of the vehicle background is described by color co-occurrence histograms. From all resulting histograms a likelihood function is calculated giving a quantity value to indicate whether the vehicle candidate is correctly classified. Only a few robust parameters have to be determined. Finally, the strategy is tested with a dataset of dense urban areas from the inner city of Munich, Germany. First results show that certain regions which are often responsible for false positive detections, such as vegetation or road markings, can be excluded successfully.

  18. 3D target tracking in infrared imagery by SIFT-based distance histograms

    NASA Astrophysics Data System (ADS)

    Yan, Ruicheng; Cao, Zhiguo

    2011-11-01

    SIFT tracking algorithm is an excellent point-based tracking algorithm, which has high tracking performance and accuracy due to its robust capability against rotation, scale change and occlusion. However, when tracking a huge 3D target in complicated real scenarios in a forward-looking infrared (FLIR) image sequence taken from an airborne moving platform, the tracked point locating in the vertical surface usually shifts away from the correct position. In this paper, we propose a novel algorithm for 3D target tracking in FLIR image sequences. Our approach uses SIFT keypoints detected in consecutive frames for point correspondence. The candidate position of the tracked point is firstly estimated by computing the affine transformation using local corresponding SIFT keypoints. Then the correct position is located via an optimal method. Euclidean distances between a candidate point and SIFT keypoints nearby are calculated and formed into a SIFT-based distance histogram. The distance histogram is defined a cost of associating each candidate point to a correct tracked point using the constraint based on the topology of each candidate point with its surrounding SIFT keypoints. Minimization of the cost is formulated as a combinatorial optimization problem. Experiments demonstrate that the proposed algorithm efficiently improves the tracking performance and accuracy.

  19. Addendum to brachytherapy dose-volume histogram commissioning with multiple planning systems.

    PubMed

    Gossman, Michael S

    2016-01-01

    The process for validating dose-volume histogram data in brachytherapy software is presented as a supplement to a previously published article. Included is the DVH accuracy evaluation of the Best NOMOS treatment planning system called "Best TPS VolumePlan." As done previously in other software, a rectangular cuboid was contoured in the treatment planning system. A single radioactive 125I source was positioned coplanar and concentric with one end. Calculations were performed to estimate dose deposition in partial volumes of the cuboid structure, using the brachytherapy dosimetry formalism defined in AAPM Task Group 43. Hand-calculated, dose-volume results were compared to TPS-generated, point-source-approximated dose-volume histogram data to establish acceptance. The required QA for commissioning was satisfied for the DVH as conducted previously for other software, using the criterion that the DVH %VolTPS "actual variance" calculations should differ by no more than 5% at any specific radial distance with respect to %VolTG-43, and the "average variance" DVH %VolTPS calculations should differ by no more than 2% over all radial distances with respect to %VolTG-43. The average disagreement observed between hand calculations and treatment planning system DVH was less than 0.5% on average for this treatment planning system and less than 1.1% maximally for 1 ≤ r ≤ 5 cm. PMID:27167288

  20. The use of force histograms for affine-invariant relative position description.

    PubMed

    Matsakis, Pascal; Keller, James M; Sjahputera, Ozy; Marjamaa, Jonathon

    2004-01-01

    Affine invariant descriptors have been widely used for recognition of objects regardless of their position, size, and orientation in space. Examples of color, texture, and shape descriptors abound in the literature. However, many tasks in computer vision require looking not only at single objects or regions in images but also at their spatial relationships. In an earlier work, we showed that the relative position of two objects can be quantitatively described by a histogram of forces. Here, we study how affine transformations affect this descriptor. The position of an object with respect to another changes when the objects are affine transformed. We analyze the link between 1) the applied affinity, 2) the relative position before transformation (described through a force histogram), and 3) the relative position after transformation. We show that any two of these elements allow the third one to be recovered. Moreover, it is possible to determine whether (or how well) two relative positions are actually related through an affine transformation. If they are not, the affinity that best approximates the unknown transformation can be retrieved, and the quality of the approximation assessed. PMID:15382682

  1. Rapid dynamic radial MRI via reference image enforced histogram constrained reconstruction

    NASA Astrophysics Data System (ADS)

    Gaass, Thomas; Bauman, Grzegorz; Potdevin, Guillaume; Noël, Peter B.; Haase, Axel

    2014-03-01

    Exploiting spatio-temporal redundancies in sub-Nyquist sampled dynamic MRI for the suppression of undersampling artifacts was shown to be of great success. However, temporally averaged and blurred structures in image space composite data poses the risk of false information in the reconstruction. Within this work we assess the possibility of employing the composite image histogram as a measure of undersampling artifacts and as basis of their suppression. The proposed algorithm utilizes a histogram, computed from a composite image within a dynamically acquired interleaved radial MRI measurement as reference to compensate for the impact of undersampling in temporally resolved data without the incorporation of temporal averaging. In addition an image space regularization utilizing a single frame low-resolution reconstruction is implemented to enforce overall contrast fidelity. The performance of the approach was evaluated on a simulated radial dynamic MRI acquisition and on two functional in vivo radial cardiac acquisitions. Results demonstrate that the algorithm maintained contrast properties, details and temporal resolution in the images, while effectively suppressing undersampling artifacts.

  2. Rapid dynamic radial MRI via reference image enforced histogram constrained reconstruction.

    PubMed

    Gaass, Thomas; Bauman, Grzegorz; Potdevin, Guillaume; Noël, Peter B; Haase, Axel

    2014-03-01

    Exploiting spatio-temporal redundancies in sub-Nyquist sampled dynamic MRI for the suppression of undersampling artifacts was shown to be of great success. However, temporally averaged and blurred structures in image space composite data poses the risk of false information in the reconstruction. Within this work we assess the possibility of employing the composite image histogram as a measure of undersampling artifacts and as basis of their suppression. The proposed algorithm utilizes a histogram, computed from a composite image within a dynamically acquired interleaved radial MRI measurement as reference to compensate for the impact of undersampling in temporally resolved data without the incorporation of temporal averaging. In addition an image space regularization utilizing a single frame low-resolution reconstruction is implemented to enforce overall contrast fidelity. The performance of the approach was evaluated on a simulated radial dynamic MRI acquisition and on two functional in vivo radial cardiac acquisitions. Results demonstrate that the algorithm maintained contrast properties, details and temporal resolution in the images, while effectively suppressing undersampling artifacts. PMID:24486719

  3. Detection of Basal Cell Carcinoma Using Color and Histogram Measures of Semitranslucent Areas

    PubMed Central

    Stoecker, William V.; Gupta, Kapil; Shrestha, Bijaya; Wronkiewiecz, Mark; Chowdhury, Raeed; Stanley, R. Joe; Xu, Jin; Moss, Randy H.; Celebi, M. Emre; Rabinovitz, Harold S.; Oliviero, Margaret; Malters, Joseph M.; Kolm, Isabel

    2009-01-01

    Background Semitranslucency, defined as a smooth, jelly-like area with varied, near-skin-tone color, can indicate a diagnosis of basal cell carcinoma (BCC) with high specificity. This study sought to analyze potential areas of semitranslucency with histogram-derived texture and color measures to discriminate BCC from non-semitranslucent areas in non-BCC skin lesions. Methods For 210 dermoscopy images, the areas of semitranslucency in 42 BCCs and comparable areas of smoothness and color in 168 non-BCCs were selected manually. Six color measures and six texture measures were applied to the semitranslucent areas of the BCC and the comparable areas in the non-BCC images. Results Receiver operating characteristic (ROC) curve analysis showed that the texture measures alone provided greater separation of BCC from non-BCC than the color measures alone. Statistical analysis showed that the four most important measures of semitranslucency are three histogram measures: contrast, smoothness, and entropy, and one color measure: blue chromaticity. Smoothness is the single most important measure. The combined 12 measures achieved a diagnostic accuracy of 95.05% based on area under the ROC curve. Conclusion Texture and color analysis measures, especially smoothness, may afford automatic detection of basal cell carcinoma images with semitranslucency. PMID:19624424

  4. European Mitochondrial DNA Haplogroups and Metabolic Changes during Antiretroviral Therapy in AIDS Clinical Trials Group Study A5142

    PubMed Central

    Hulgan, Todd; Haubrich, Richard; Riddler, Sharon A.; Tebas, Pablo; Ritchie, Marylyn D.; McComsey, Grace A.; Haas, David W.; Canter, Jeffrey A.

    2010-01-01

    Background Mitochondrial DNA (mtDNA) influences metabolic diseases and perhaps antiretroviral therapy (ART) complications. We explored associations between European mtDNA haplogroups and metabolic changes among A5142 participants. Methods 757 ART-naïve subjects were randomized to one of three class-sparing ART regimens including efavirenz and/or lopinavir/ritonavir with or without nucleoside reverse transcriptase inhibitors (NRTIs). Non-randomized NRTIs included stavudine, tenofovir, or zidovudine, each with lamivudine. Fasting lipid profiles and whole-body dual-energy X-ray absorptiometry (DEXA) were performed. Nine European mtDNA haplogroups were determined for 231 self-identified non-Hispanic white subjects. Metabolic changes from baseline to 96 weeks were analyzed by haplogroup. Results Median age was 39 years, 9% were female, and 37%, 32%, and 30% were randomized to NRTI-containing regimens with either efavirenz or lopinavir/ritonavir, and an NRTI-sparing regimen respectively. Among NRTI-containing regimens, 51% included zidovudine, 28% tenofovir, and 21% stavudine. Compared with other haplogroups, mtDNA haplogroup I (N=10) had higher baseline non-HDL cholesterol (160 mg/dL [interquartile range 137–171] vs. 120 mg/dL [104–136]; p=0.005), a decrease in non-HDL cholesterol over 96 weeks (−14% [−20-+6] vs. +25% [+8-+51]; p<0.001), tended to have more baseline extremity fat, and had more extremity fat loss by DEXA (−13% [−31-+12] vs. +9% [−13-+26]; p=0.08) and lipoatrophy (50% vs. 20%; p=0.04). Haplogroup W (N=5; all randomized to NRTI-sparing regimens) had the greatest increase in extremity fat (+35.5% [+26.8 - +54.9]; P=0.02). Conclusions Lipids and extremity fat were associated with European mtDNA haplogroups in this HIV-infected population. These preliminary results suggest that mitochondrial genomics may influence metabolic parameters before and during ART. PMID:20871389

  5. RelMon: A General Approach to QA, Validation and Physics Analysis through Comparison of large Sets of Histograms

    NASA Astrophysics Data System (ADS)

    Piparo, Danilo

    2012-12-01

    The estimation of the compatibility of large amounts of histogram pairs is a recurrent problem in high energy physics. The issue is common to several different areas, from software quality monitoring to data certification, preservation and analysis. Given two sets of histograms, it is very important to be able to scrutinize the outcome of several goodness of fit tests, obtain a clear answer about the overall compatibility, easily spot the single anomalies and directly access the concerned histogram pairs. This procedure must be automated in order to reduce the human workload, therefore improving the process of identification of differences which is usually carried out by a trained human mind. Some solutions to this problem have been proposed, but they are experiment specific. RelMon depends only on ROOT and offers several goodness of fit tests (e.g. chi-squared or Kolmogorov-Smirnov). It produces highly readable web reports, in which aggregations of the comparisons rankings are available as well as all the plots of the single histogram overlays. The comparison procedure is fully automatic and scales smoothly towards ensembles of millions of histograms. Examples of RelMon utilisation within the regular workflows of the CMS collaboration and the advantages therewith obtained are described. Its interplay with the data quality monitoring infrastructure is illustrated as well as its role in the QA of the event reconstruction code, its integration in the CMS software release cycle process, CMS user data analysis and dataset validation.

  6. Fluorogenic Real-Time Reporters of DNA Repair by MGMT, a Clinical Predictor of Antitumor Drug Response.

    PubMed

    Beharry, Andrew A; Nagel, Zachary D; Samson, Leona D; Kool, Eric T

    2016-01-01

    Common alkylating antitumor drugs, such as temozolomide, trigger their cytotoxicity by methylating the O6-position of guanosine in DNA. However, the therapeutic effect of these drugs is dampened by elevated levels of the DNA repair enzyme, O6-methylguanine DNA methyltransferase (MGMT), which directly reverses this alkylation. As a result, assessing MGMT levels in patient samples provides an important predictor of therapeutic response; however, current methods available to measure this protein are indirect, complex and slow. Here we describe the design and synthesis of fluorescent chemosensors that report directly on MGMT activity in a single step within minutes. The chemosensors incorporate a fluorophore and quencher pair, which become separated by the MGMT dealkylation reaction, yielding light-up responses of up to 55-fold, directly reflecting repair activity. Experiments show that the best-performing probe retains near-native activity at mid-nanomolar concentrations. A nuclease-protected probe, NR-1, was prepared and tested in tumor cell lysates, demonstrating an ability to evaluate relative levels of MGMT repair activity in twenty minutes. In addition, a probe was employed to evaluate inhibitors of MGMT, suggesting utility for discovering new inhibitors in a high-throughput manner. Probe designs such as that of NR-1 may prove valuable to clinicians in selection of patients for alkylating drug therapies and in assessing resistance that arises during treatment. PMID:27035132

  7. Fluorogenic Real-Time Reporters of DNA Repair by MGMT, a Clinical Predictor of Antitumor Drug Response

    PubMed Central

    Beharry, Andrew A.; Nagel, Zachary D.; Samson, Leona D.; Kool, Eric T.

    2016-01-01

    Common alkylating antitumor drugs, such as temozolomide, trigger their cytotoxicity by methylating the O6-position of guanosine in DNA. However, the therapeutic effect of these drugs is dampened by elevated levels of the DNA repair enzyme, O6-methylguanine DNA methyltransferase (MGMT), which directly reverses this alkylation. As a result, assessing MGMT levels in patient samples provides an important predictor of therapeutic response; however, current methods available to measure this protein are indirect, complex and slow. Here we describe the design and synthesis of fluorescent chemosensors that report directly on MGMT activity in a single step within minutes. The chemosensors incorporate a fluorophore and quencher pair, which become separated by the MGMT dealkylation reaction, yielding light-up responses of up to 55-fold, directly reflecting repair activity. Experiments show that the best-performing probe retains near-native activity at mid-nanomolar concentrations. A nuclease-protected probe, NR-1, was prepared and tested in tumor cell lysates, demonstrating an ability to evaluate relative levels of MGMT repair activity in twenty minutes. In addition, a probe was employed to evaluate inhibitors of MGMT, suggesting utility for discovering new inhibitors in a high-throughput manner. Probe designs such as that of NR-1 may prove valuable to clinicians in selection of patients for alkylating drug therapies and in assessing resistance that arises during treatment. PMID:27035132

  8. Inhibition of DNA-repair genes Ercc1 and Mgmt enhances temozolomide efficacy in gliomas treatment: a pre-clinical study

    PubMed Central

    Boccard, Sandra G.; Marand, Sandie V.; Geraci, Sandra; Pycroft, Laurie; Berger, François R.; Pelletier, Laurent A.

    2015-01-01

    Gliomas are the most common primary brain tumors. To date, therapies do not allow curing patients, and glioblastomas (GBMs) are associated with remarkably poor prognosis. This situation is at least partly due to intrinsic or acquired resistance to treatment, especially to chemotherapy. In 2005, temozolomide (TMZ) has become the first chemotherapeutic drug validated for GBM. Nevertheless TMZ efficacy depends on Mgmt status. While the methylation of Mgmt promoter was considered so far as a prognostic marker, its targeting is becoming an effective therapeutic opportunity. Thus, arrival of both TMZ and Mgmt illustrated that considerable progress can still be realized by optimizing adjuvant chemotherapy. A part of this progress could be accomplished in the future by overcoming residual resistance. The aim of the present study was to investigate the involvement of a set of other DNA-repair genes in glioma resistance to temozolomide. We focused on DNA-repair genes located in the commonly deleted chromosomal region in oligodendroglioma (1p/19q) highly correlated with patient response to chemotherapy. We measured effects of inhibition of ten DNA-repair genes expression using siRNAs on astrocytoma cell response to cisplatin (CDDP) and TMZ. SiRNAs targeting ercc1, ercc2, mutyh, and pnkp significantly sensitized cells to chemotherapy, increasing cell death by up to 25%. In vivo we observed a decrease of subcutaneous glioma tumor growth after injection of siRNA in conjunction with absorption of TMZ. We demonstrated in this pre-clinical study that targeting of DNA-repair genes such as Ercc1 could be used as an adjuvant chemosensitization treatment, similarly to Mgmt inhibition. PMID:26336131

  9. Inhibition of DNA-repair genes Ercc1 and Mgmt enhances temozolomide efficacy in gliomas treatment: a pre-clinical study.

    PubMed

    Boccard, Sandra G; Marand, Sandie V; Geraci, Sandra; Pycroft, Laurie; Berger, François R; Pelletier, Laurent A

    2015-10-01

    Gliomas are the most common primary brain tumors. To date, therapies do not allow curing patients, and glioblastomas (GBMs) are associated with remarkably poor prognosis. This situation is at least partly due to intrinsic or acquired resistance to treatment, especially to chemotherapy. In 2005, temozolomide (TMZ) has become the first chemotherapeutic drug validated for GBM. Nevertheless TMZ efficacy depends on Mgmt status. While the methylation of Mgmt promoter was considered so far as a prognostic marker, its targeting is becoming an effective therapeutic opportunity. Thus, arrival of both TMZ and Mgmt illustrated that considerable progress can still be realized by optimizing adjuvant chemotherapy. A part of this progress could be accomplished in the future by overcoming residual resistance. The aim of the present study was to investigate the involvement of a set of other DNA-repair genes in glioma resistance to temozolomide. We focused on DNA-repair genes located in the commonly deleted chromosomal region in oligodendroglioma (1p/19q) highly correlated with patient response to chemotherapy. We measured effects of inhibition of ten DNA-repair genes expression using siRNAs on astrocytoma cell response to cisplatin (CDDP) and TMZ. SiRNAs targeting ercc1, ercc2, mutyh, and pnkp significantly sensitized cells to chemotherapy, increasing cell death by up to 25%. In vivo we observed a decrease of subcutaneous glioma tumor growth after injection of siRNA in conjunction with absorption of TMZ. We demonstrated in this pre-clinical study that targeting of DNA-repair genes such as Ercc1 could be used as an adjuvant chemosensitization treatment, similarly to Mgmt inhibition. PMID:26336131

  10. Impact of the radiotherapy technique on the correlation between dose-volume histograms of the bladder wall defined on MRI imaging and dose-volume/surface histograms in prostate cancer patients

    NASA Astrophysics Data System (ADS)

    Maggio, Angelo; Carillo, Viviana; Cozzarini, Cesare; Perna, Lucia; Rancati, Tiziana; Valdagni, Riccardo; Gabriele, Pietro; Fiorino, Claudio

    2013-04-01

    The aim of this study was to evaluate the correlation between the ‘true’ absolute and relative dose-volume histograms (DVHs) of the bladder wall, dose-wall histogram (DWH) defined on MRI imaging and other surrogates of bladder dosimetry in prostate cancer patients, planned both with 3D-conformal and intensity-modulated radiation therapy (IMRT) techniques. For 17 prostate cancer patients, previously treated with radical intent, CT and MRI scans were acquired and matched. The contours of bladder walls were drawn by using MRI images. External bladder surfaces were then used to generate artificial bladder walls by performing automatic contractions of 5, 7 and 10 mm. For each patient a 3D conformal radiotherapy (3DCRT) and an IMRT treatment plan was generated with a prescription dose of 77.4 Gy (1.8 Gy/fr) and DVH of the whole bladder of the artificial walls (DVH-5/10) and dose-surface histograms (DSHs) were calculated and compared against the DWH in absolute and relative value, for both treatment planning techniques. A specific software (VODCA v. 4.4.0, MSS Inc.) was used for calculating the dose-volume/surface histogram. Correlation was quantified for selected dose-volume/surface parameters by the Spearman correlation coefficient. The agreement between %DWH and DVH5, DVH7 and DVH10 was found to be very good (maximum average deviations below 2%, SD < 5%): DVH5 showed the best agreement. The correlation was slightly better for absolute (R = 0.80-0.94) compared to relative (R = 0.66-0.92) histograms. The DSH was also found to be highly correlated with the DWH, although slightly higher deviations were generally found. The DVH was not a good surrogate of the DWH (R < 0.7 for most of parameters). When comparing the two treatment techniques, more pronounced differences between relative histograms were seen for IMRT with respect to 3DCRT (p < 0.0001).

  11. Clinical and Molecular Characteristics in 100 Chinese Pediatric Patients with m.3243A>G Mutation in Mitochondrial DNA

    PubMed Central

    Xia, Chang-Yu; Liu, Yu; Liu, Hui; Zhang, Yan-Chun; Ma, Yi-Nan; Qi, Yu

    2016-01-01

    Background: Mitochondrial diseases are a group of energy metabolic disorders with multisystem involvements. Variable clinical features present a major challenge in pediatric diagnoses. We summarized the clinical spectrum of m.3243A>G mutation in Chinese pediatric patients, to define the common clinical manifestations and study the correlation between heteroplasmic degree of the mutation and clinical severity of the disease. Methods: Clinical data of one-hundred pediatric patients with symptomatic mitochondrial disease harboring m.3243A>G mutation from 2007 to 2013 were retrospectively reviewed. Detection of m.3243A>G mutation ratio was performed by polymerase chain reaction (PCR)-restriction fragment length polymorphism. Correlation between m.3243A>G mutation ratio and age was evaluated. The differences in clinical symptom frequency of patients with low, middle, and high levels of mutation ratio were analyzed by Chi-square test. Results: Sixty-six patients (66%) had suffered a delayed diagnosis for an average of 2 years. The most frequent symptoms were seizures (76%), short stature (73%), elevated plasma lactate (70%), abnormal magnetic resonance imaging/computed tomography (MRI/CT) changes (68%), vomiting (55%), decreased vision (52%), headache (50%), and muscle weakness (48%). The mutation ratio was correlated negatively with onset age (r = −0.470, P < 0.001). Myopathy was more frequent in patients with a high level of mutation ratio. However, patients with a low or middle level of m.3243A>G mutation ratio were more likely to suffer hearing loss, decreased vision, and gastrointestinal disturbance than patients with a high level of mutation ratio. Conclusions: Our study showed that half of Chinese pediatric patients with m.3243A>G mutation presented seizures, short stature, abnormal MRI/CT changes, elevated plasma lactate, vomiting, and headache. Pediatric patients with these recurrent symptoms should be considered for screening m.3243A>G mutation. Clinical

  12. The characterization of radioaerosol deposition in the healthy lung by histogram distribution analysis

    SciTech Connect

    Garrard, C.S.; Gerrity, T.R.; Schreiner, J.F.; Yeates, D.B.

    1981-12-01

    Thirteen healthy nonsmoking volunteers inhaled an 8.1 micrometers (MMAD) radioaerosol on two occasions. Aerosol deposition pattern within the right lung, as recorded by a gamma camera, was expressed as the 3rd and 4th moments of the distribution histogram (skew and kurtosis) of radioactivity during the first ten minutes after aerosol inhalation. Deposition pattern was also expressed as the percentage of deposited activity retained within the lung at 24 hr (24 hr % retention) and found to be significantly correlated with measures of skew (P less than 0.001). Tests of pulmonary function (FEV1, FVC, and MMFR) were significantly correlated with skew. Correlations were also demonstrated for these pulmonary function tests with 24 hr % retention but at lower levels of significance. Results indicate that changes in measures of forced expiratory airflow in healthy human volunteers influence deposition pattern and that the skew of the distribution of inhaled radioactivity may provide an acceptable index of deposition pattern.

  13. Scale and Orientation-Based Background Weighted Histogram for Human Tracking

    NASA Astrophysics Data System (ADS)

    Laaroussi, Khadija; Saaidi, Abderrahim; Masrar, Mohamed; Satori, Khalid

    2016-09-01

    The Mean Shift procedure is a popular object tracking algorithm since it is fast, easy to implement and performs well in a range of conditions. However, classic Mean Shift tracking algorithm fixes the size and orientation of the tracking window, which limits the performance when the target's orientation and scale change. In this paper, we present a new human tracking algorithm based on Mean Shift technique in order to estimate the position, scale and orientation changes of the target. This work combines moment features of the weight image with background information to design a robust tracking algorithm entitled Scale and Orientation-based Background Weighted Histogram (SOBWH). The experimental results show that the proposed approach SOBWH presents a good compromise between tracking precision and calculation time, also they validate its robustness, especially to large background variation, scale and orientation changes and similar background scenes.

  14. ``Binless Wang-Landau sampling'' - a multicanonical Monte Carlo algorithm without histograms

    NASA Astrophysics Data System (ADS)

    Li, Ying Wai; Eisenbach, Markus

    Inspired by the very successful Wang-Landau (WL) sampling, we innovated a multicanonical Monte Carlo algorithm to obtain the density of states (DOS) for physical systems with continuous state variables. Unlike the original WL scheme where the DOS is obtained as a numerical array of finite resolution, our algorithm assumes an analytical form for the DOS using a well chosen basis set, with coefficients determined iteratively similar to the WL approach. To avoid undesirable artificial errors caused by the discretization of state variables, we get rid of the use of a histogram for keeping track of the number of visits to energy levels, but store the visited states directly for the fitting of coefficients. This new algorithm has the advantage of producing an analytical expression for the DOS, while the original WL sampling can be readily recovered. This research was supported by the Office of Science of the Department of Energy under Contract DE-AC05-00OR22725.

  15. An introduction to RHINO: real-time histogram interpretation of numerical observations

    NASA Astrophysics Data System (ADS)

    Chandler, Susan; Lukesh, Gordon

    2006-02-01

    RHINO, Real-time Histogram Interpretation of Numerical Observations, is a specialty algorithm and tool under development for the United States Air Force Office of Scientific Research. The intent is to provide real-time feedback for adaptive control of telescope pointing for ground-space-ground laser illumination experiments. Nukove together with New Mexico State University first established a proof-of-principle laboratory experiment using RHINO and, under a controlled environment, reduction of the pointing error known as boresight was demonstrated. Additionally, the RHINO algorithm successfully predicted a systematic pointing offset due to solar illumination of a satellite. RHINO is resilient to effects such as glints, speckle, and scintillation. The forthcoming commercially available version of RHINO will use real-time field data and provide adaptive control to the user.

  16. Biological dose volume histograms during conformal hypofractionated accelerated radiotherapy for prostate cancer

    SciTech Connect

    Koukourakis, Michael I.; Abatzoglou, Ioannis; Touloupidis, Stavros; Manavis, Ioannis

    2007-01-15

    Radiobiological data suggest that prostate cancer has a low {alpha}/{beta} ratio. Large radiotherapy fractions may, therefore, prove more efficacious than standard radiotherapy, while radiotherapy acceleration should further improve control rates. This study describes the radiobiology of a conformal hypofractionated accelerated radiotherapy scheme for the treatment of high risk prostate cancer. Anteroposterior fields to the pelvis deliver a daily dose of 2.7 Gy, while lateral fields confined to the prostate and seminal vesicles deliver an additional daily dose of 0.7 Gy. Radiotherapy is accomplished within 19 days (15 fractions). Dose volume histograms, calculated for tissue specific {alpha}/{beta} ratios and time factors, predict a high biological dose to the prostate and seminal vesicles (77-93 Gy). The biological dose to normal pelvic tissues is maintained at standard levels. Radiobiological dosimetry suggests that, using hypofractionated and accelerated radiotherapy, high biological radiation dose can be given to the prostate without overdosing normal tissues.

  17. Wavelength-adaptive dehazing using histogram merging-based classification for UAV images.

    PubMed

    Yoon, Inhye; Jeong, Seokhwa; Jeong, Jaeheon; Seo, Doochun; Paik, Joonki

    2015-01-01

    Since incoming light to an unmanned aerial vehicle (UAV) platform can be scattered by haze and dust in the atmosphere, the acquired image loses the original color and brightness of the subject. Enhancement of hazy images is an important task in improving the visibility of various UAV images. This paper presents a spatially-adaptive dehazing algorithm that merges color histograms with consideration of the wavelength-dependent atmospheric turbidity. Based on the wavelength-adaptive hazy image acquisition model, the proposed dehazing algorithm consists of three steps: (i) image segmentation based on geometric classes; (ii) generation of the context-adaptive transmission map; and (iii) intensity transformation for enhancing a hazy UAV image. The major contribution of the research is a novel hazy UAV image degradation model by considering the wavelength of light sources. In addition, the proposed transmission map provides a theoretical basis to differentiate visually important regions from others based on the turbidity and merged classification results. PMID:25808767

  18. A 124 Mpixels/s VLSI design for histogram-based joint bilateral filtering.

    PubMed

    Tseng, Yu-Cheng; Hsu, Po-Hsiung; Chang, Tian-Sheuan

    2011-11-01

    This paper presents an efficient and scalable design for histogram-based bilateral filtering (BF) and joint BF (JBF) by memory reduction methods and architecture design techniques to solve the problems of high memory cost, high computational complexity, high bandwidth, and large range table. The presented memory reduction methods exploit the progressive computing characteristics to reduce the memory cost to 0.003%-0.020%, as compared with the original approach. Furthermore, the architecture design techniques adopt range domain parallelism and take advantage of the computing order and the numerical properties to solve the complexity, bandwidth, and range-table problems. The example design with a 90-nm complementary metal-oxide-semiconductor process can deliver the throughput to 124 Mpixels/s with 356-K gate counts and 23-KB on-chip memory. PMID:21659030

  19. Wavelength-Adaptive Dehazing Using Histogram Merging-Based Classification for UAV Images

    PubMed Central

    Yoon, Inhye; Jeong, Seokhwa; Jeong, Jaeheon; Seo, Doochun; Paik, Joonki

    2015-01-01

    Since incoming light to an unmanned aerial vehicle (UAV) platform can be scattered by haze and dust in the atmosphere, the acquired image loses the original color and brightness of the subject. Enhancement of hazy images is an important task in improving the visibility of various UAV images. This paper presents a spatially-adaptive dehazing algorithm that merges color histograms with consideration of the wavelength-dependent atmospheric turbidity. Based on the wavelength-adaptive hazy image acquisition model, the proposed dehazing algorithm consists of three steps: (i) image segmentation based on geometric classes; (ii) generation of the context-adaptive transmission map; and (iii) intensity transformation for enhancing a hazy UAV image. The major contribution of the research is a novel hazy UAV image degradation model by considering the wavelength of light sources. In addition, the proposed transmission map provides a theoretical basis to differentiate visually important regions from others based on the turbidity and merged classification results. PMID:25808767

  20. Accelerating the weighted histogram analysis method by direct inversion in the iterative subspace

    PubMed Central

    Zhang, Cheng; Lai, Chun-Liang; Pettitt, B. Montgomery

    2016-01-01

    The weighted histogram analysis method (WHAM) for free energy calculations is a valuable tool to produce free energy differences with the minimal errors. Given multiple simulations, WHAM obtains from the distribution overlaps the optimal statistical estimator of the density of states, from which the free energy differences can be computed. The WHAM equations are often solved by an iterative procedure. In this work, we use a well-known linear algebra algorithm which allows for more rapid convergence to the solution. We find that the computational complexity of the iterative solution to WHAM and the closely-related multiple Bennett acceptance ratio (MBAR) method can be improved by using the method of direct inversion in the iterative subspace. We give examples from a lattice model, a simple liquid and an aqueous protein solution. PMID:27453632

  1. A fracture enhancement method based on the histogram equalization of eigenstructure-based coherence

    NASA Astrophysics Data System (ADS)

    Dou, Xi-Ying; Han, Li-Guo; Wang, En-Li; Dong, Xue-Hua; Yang, Qing; Yan, Gao-Han

    2014-06-01

    Eigenstructure-based coherence attributes are efficient and mature techniques for large-scale fracture detection. However, in horizontally bedded and continuous strata, buried fractures in high grayscale value zones are difficult to detect. Furthermore, middle- and small-scale fractures in fractured zones where migration image energies are usually not concentrated perfectly are also hard to detect because of the fuzzy, clouded shadows owing to low grayscale values. A new fracture enhancement method combined with histogram equalization is proposed to solve these problems. With this method, the contrast between discontinuities and background in coherence images is increased, linear structures are highlighted by stepwise adjustment of the threshold of the coherence image, and fractures are detected at different scales. Application of the method shows that it can also improve fracture cognition and accuracy.

  2. Improving the imaging of calcifications in CT by histogram-based selective deblurring

    NASA Astrophysics Data System (ADS)

    Rollano-Hijarrubia, Empar; van der Meer, Frits; van der Lugt, Add; Weinans, Harrie; Vrooman, Henry; Vossepoel, Albert; Stokking, Rik

    2005-04-01

    Imaging of small high-density structures, such as calcifications, with computed tomography (CT) is limited by the spatial resolution of the system. Blur causes small calcifications to be imaged with lower contrast and overestimated volume, thereby hampering the analysis of vessels. The aim of this work is to reduce the blur of calcifications by applying three-dimensional (3D) deconvolution. Unfortunately, the high-frequency amplification of the deconvolution produces edge-related ring artifacts and enhances noise and original artifacts, which degrades the imaging of low-density structures. A method, referred to as Histogram-based Selective Deblurring (HiSD), was implemented to avoid these negative effects. HiSD uses the histogram information to generate a restored image in which the low-intensity voxel information of the observed image is combined with the high-intensity voxel information of the deconvolved image. To evaluate HiSD we scanned four in-vitro atherosclerotic plaques of carotid arteries with a multislice spiral CT and with a microfocus CT (μCT), used as reference. Restored images were generated from the observed images, and qualitatively and quantitatively compared with their corresponding μCT images. Transverse views and maximum-intensity projections of restored images show the decrease of blur of the calcifications in 3D. Measurements of the areas of 27 calcifications and total volumes of calcification of 4 plaques show that the overestimation of calcification was smaller for restored images (mean-error: 90% for area; 92% for volume) than for observed images (143%; 213%, respectively). The qualitative and quantitative analyses show that the imaging of calcifications in CT can be improved considerably by applying HiSD.

  3. Fast Analysis of Molecular Dynamics Trajectories with Graphics Processing Units—Radial Distribution Function Histogramming

    PubMed Central

    Stone, John E.; Kohlmeyer, Axel

    2011-01-01

    The calculation of radial distribution functions (RDFs) from molecular dynamics trajectory data is a common and computationally expensive analysis task. The rate limiting step in the calculation of the RDF is building a histogram of the distance between atom pairs in each trajectory frame. Here we present an implementation of this histogramming scheme for multiple graphics processing units (GPUs). The algorithm features a tiling scheme to maximize the reuse of data at the fastest levels of the GPU’s memory hierarchy and dynamic load balancing to allow high performance on heterogeneous configurations of GPUs. Several versions of the RDF algorithm are presented, utilizing the specific hardware features found on different generations of GPUs. We take advantage of larger shared memory and atomic memory operations available on state-of-the-art GPUs to accelerate the code significantly. The use of atomic memory operations allows the fast, limited-capacity on-chip memory to be used much more efficiently, resulting in a fivefold increase in performance compared to the version of the algorithm without atomic operations. The ultimate version of the algorithm running in parallel on four NVIDIA GeForce GTX 480 (Fermi) GPUs was found to be 92 times faster than a multithreaded implementation running on an Intel Xeon 5550 CPU. On this multi-GPU hardware, the RDF between two selections of 1,000,000 atoms each can be calculated in 26.9 seconds per frame. The multi-GPU RDF algorithms described here are implemented in VMD, a widely used and freely available software package for molecular dynamics visualization and analysis. PMID:21547007

  4. Convergence and error estimation in free energy calculations using the weighted histogram analysis method

    PubMed Central

    Zhu, Fangqiang; Hummer, Gerhard

    2012-01-01

    The weighted histogram analysis method (WHAM) has become the standard technique for the analysis of umbrella sampling simulations. In this paper, we address the challenges (1) of obtaining fast and accurate solutions of the coupled nonlinear WHAM equations, (2) of quantifying the statistical errors of the resulting free energies, (3) of diagnosing possible systematic errors, and (4) of optimal allocation of the computational resources. Traditionally, the WHAM equations are solved by a fixed-point direct iteration method, despite poor convergence and possible numerical inaccuracies in the solutions. Here we instead solve the mathematically equivalent problem of maximizing a target likelihood function, by using superlinear numerical optimization algorithms with a significantly faster convergence rate. To estimate the statistical errors in one-dimensional free energy profiles obtained from WHAM, we note that for densely spaced umbrella windows with harmonic biasing potentials, the WHAM free energy profile can be approximated by a coarse-grained free energy obtained by integrating the mean restraining forces. The statistical errors of the coarse-grained free energies can be estimated straightforwardly and then used for the WHAM results. A generalization to multidimensional WHAM is described. We also propose two simple statistical criteria to test the consistency between the histograms of adjacent umbrella windows, which help identify inadequate sampling and hysteresis in the degrees of freedom orthogonal to the reaction coordinate. Together, the estimates of the statistical errors and the diagnostics of inconsistencies in the potentials of mean force provide a basis for the efficient allocation of computational resources in free energy simulations. PMID:22109354

  5. Seismic remote sensing image segmentation based on spectral histogram and dynamic region merging

    NASA Astrophysics Data System (ADS)

    Wang, Peng; Sun, Genyun; Wang, Zhenjie

    2015-12-01

    Image segmentation is the foundation of seismic information extraction from high-resolution remote sensing images. While the complexity of the seismic image brings great challenges to its segmentation. Compared with the traditional pixel-level approaches, the region-level approaches are found prevailing in dealing with the complexity. This paper addresses the seismic image segmentation problem in a region-merging style. Starting from many over-segmented regions, the image segmentation is performed by iteratively merging the neighboring regions. In the proposed algorithm, the merging criterion and merging order are two essential issues to be emphatically considered. An effective merging criterion is largely depends on the region feature and neighbor homogeneity measure. The region's spectral histogram represents the global feature of each region and enhances the discriminability of neighboring regions. Therefore, we utilize it to solve the merging criterion. Under a certain the merging criterion, a better performance could be obtained if the most similar regions are always ensured to be merged first, which can be transformed into a least-cost problem. Rather than predefine an order queue, we solve the order problem with a dynamic scheme. The proposed approach mainly contains three parts. Firstly, starting from the over-segmented regions, the spectral histograms are constructed to represent each region. Then, we use the homogeneity that combines the distance and shape measure to conduct the merge criterion. Finally, neighbor regions are dynamically merged following the dynamic program (DP) theory and breadth-first strategy. Experiments are conducted using the earthquake images, including collapsed buildings and seismic secondary geological disaster. The experimental results show that, the proposed method segments the seismic image more correctly.

  6. Fast Analysis of Molecular Dynamics Trajectories with Graphics Processing Units-Radial Distribution Function Histogramming.

    PubMed

    Levine, Benjamin G; Stone, John E; Kohlmeyer, Axel

    2011-05-01

    The calculation of radial distribution functions (RDFs) from molecular dynamics trajectory data is a common and computationally expensive analysis task. The rate limiting step in the calculation of the RDF is building a histogram of the distance between atom pairs in each trajectory frame. Here we present an implementation of this histogramming scheme for multiple graphics processing units (GPUs). The algorithm features a tiling scheme to maximize the reuse of data at the fastest levels of the GPU's memory hierarchy and dynamic load balancing to allow high performance on heterogeneous configurations of GPUs. Several versions of the RDF algorithm are presented, utilizing the specific hardware features found on different generations of GPUs. We take advantage of larger shared memory and atomic memory operations available on state-of-the-art GPUs to accelerate the code significantly. The use of atomic memory operations allows the fast, limited-capacity on-chip memory to be used much more efficiently, resulting in a fivefold increase in performance compared to the version of the algorithm without atomic operations. The ultimate version of the algorithm running in parallel on four NVIDIA GeForce GTX 480 (Fermi) GPUs was found to be 92 times faster than a multithreaded implementation running on an Intel Xeon 5550 CPU. On this multi-GPU hardware, the RDF between two selections of 1,000,000 atoms each can be calculated in 26.9 seconds per frame. The multi-GPU RDF algorithms described here are implemented in VMD, a widely used and freely available software package for molecular dynamics visualization and analysis. PMID:21547007

  7. Fast analysis of molecular dynamics trajectories with graphics processing units-Radial distribution function histogramming

    SciTech Connect

    Levine, Benjamin G.; Stone, John E.; Kohlmeyer, Axel

    2011-05-01

    The calculation of radial distribution functions (RDFs) from molecular dynamics trajectory data is a common and computationally expensive analysis task. The rate limiting step in the calculation of the RDF is building a histogram of the distance between atom pairs in each trajectory frame. Here we present an implementation of this histogramming scheme for multiple graphics processing units (GPUs). The algorithm features a tiling scheme to maximize the reuse of data at the fastest levels of the GPU's memory hierarchy and dynamic load balancing to allow high performance on heterogeneous configurations of GPUs. Several versions of the RDF algorithm are presented, utilizing the specific hardware features found on different generations of GPUs. We take advantage of larger shared memory and atomic memory operations available on state-of-the-art GPUs to accelerate the code significantly. The use of atomic memory operations allows the fast, limited-capacity on-chip memory to be used much more efficiently, resulting in a fivefold increase in performance compared to the version of the algorithm without atomic operations. The ultimate version of the algorithm running in parallel on four NVIDIA GeForce GTX 480 (Fermi) GPUs was found to be 92 times faster than a multithreaded implementation running on an Intel Xeon 5550 CPU. On this multi-GPU hardware, the RDF between two selections of 1,000,000 atoms each can be calculated in 26.9 s per frame. The multi-GPU RDF algorithms described here are implemented in VMD, a widely used and freely available software package for molecular dynamics visualization and analysis.

  8. Performance analysis of a dual-tree algorithm for computing spatial distance histograms.

    PubMed

    Chen, Shaoping; Tu, Yi-Cheng; Xia, Yuni

    2011-08-01

    Many scientific and engineering fields produce large volume of spatiotemporal data. The storage, retrieval, and analysis of such data impose great challenges to database systems design. Analysis of scientific spatiotemporal data often involves computing functions of all point-to-point interactions. One such analytics, the Spatial Distance Histogram (SDH), is of vital importance to scientific discovery. Recently, algorithms for efficient SDH processing in large-scale scientific databases have been proposed. These algorithms adopt a recursive tree-traversing strategy to process point-to-point distances in the visited tree nodes in batches, thus require less time when compared to the brute-force approach where all pairwise distances have to be computed. Despite the promising experimental results, the complexity of such algorithms has not been thoroughly studied. In this paper, we present an analysis of such algorithms based on a geometric modeling approach. The main technique is to transform the analysis of point counts into a problem of quantifying the area of regions where pairwise distances can be processed in batches by the algorithm. From the analysis, we conclude that the number of pairwise distances that are left to be processed decreases exponentially with more levels of the tree visited. This leads to the proof of a time complexity lower than the quadratic time needed for a brute-force algorithm and builds the foundation for a constant-time approximate algorithm. Our model is also general in that it works for a wide range of point spatial distributions, histogram types, and space-partitioning options in building the tree. PMID:21804753

  9. The retina dose-area histogram: a metric for quantitatively comparing rival eye plaque treatment options

    PubMed Central

    2013-01-01

    Purpose Episcleral plaques have a history of over a half century in the delivery of radiation therapy to intraocular tumors such as choroidal melanoma. Although the tumor control rate is high, vision-impairing complications subsequent to treatment remain an issue. Notable, late complications are radiation retinopathy and maculopathy. The obvious way to reduce the risk of radiation damage to the retina is to conform the prescribed isodose surface to the tumor base and to reduce the dose delivered to the surrounding healthy retina, especially the macula. Using a fusion of fundus photography, ultrasound and CT images, tumor size, shape and location within the eye can be accurately simulated as part of the radiation planning process. In this work an adaptation of the dose-volume histogram (DVH), the retina dose-area histogram (RDAH) is introduced as a metric to help compare rival plaque designs and conformal treatment planning options with the goal of reducing radiation retinopathy. Material and methods The RDAH is calculated by transforming a digitized fundus-photo collage of the tumor into a rasterized polar map of the retinal surface known as a retinal diagram (RD). The perimeter of the tumor base is digitized on the RD and its area computed. Area and radiation dose are calculated for every pixel in the RD. Results The areal resolution of the RDAH is a function of the pixel resolution of the raster image used to display the RD and the number of polygon edges used to digitize the perimeter of the tumor base. A practical demonstration is presented. Conclusions The RDAH provides a quantitative metric by which episcleral plaque treatment plan options may be evaluated and compared in order to confirm adequate dosimetric coverage of the tumor and margin, and to help minimize dose to the macula and retina. PMID:23634152

  10. Size distribution of linear and helical polymers in actin solution analyzed by photon counting histogram.

    PubMed

    Terada, Naofumi; Shimozawa, Togo; Ishiwata, Shin'ichi; Funatsu, Takashi

    2007-03-15

    Actin is a ubiquitous protein that is a major component of the cytoskeleton, playing an important role in muscle contraction and cell motility. At steady state, actin monomers and filaments (F-actin) coexist, and actin subunits continuously attach and detach at the filament ends. However, the size distribution of actin oligomers in F-actin solution has never been clarified. In this study, we investigated the size distribution of actin oligomers using photon-counting histograms. For this purpose, actin was labeled with a fluorescent dye, and the emitted photons were detected by confocal optics (the detection volume was of femtoliter (fL) order). Photon-counting histograms were analyzed to obtain the number distribution of actin oligomers in the detection area from their brightness, assuming that the brightness of an oligomer was proportional to the number of protomers. We found that the major populations at physiological ionic strength were 1-5mers. For data analysis, we successfully applied the theory of linear and helical aggregations of macromolecules. The model postulates three states of actin, i.e., monomers, linear polymers, and helical polymers. Here we obtained three parameters: the equilibrium constants for polymerization of linear polymers, K(l)=(5.2 +/- 1.1) x 10(6) M(-1), and helical polymers, K(h)=(1.6 +/- 0.5) x 10(7) M(-1); and the ratio of helical to linear trimers, gamma = (3.6 +/- 2.3) x 10(-2). The excess free energy of transforming a linear trimer to a helical trimer, which is assumed to be a nucleus for helical polymers, was calculated to be 2.0 kcal/mol. These analyses demonstrate that the oligomeric phase at steady state is predominantly composed of linear 1-5mers, and the transition from linear to helical polymers occurs on the level of 5-7mers. PMID:17172301

  11. DNA Binding to the Silica Surface.

    PubMed

    Shi, Bobo; Shin, Yun Kyung; Hassanali, Ali A; Singer, Sherwin J

    2015-08-27

    We investigate the DNA-silica binding mechanism using molecular dynamics simulations. This system is of technological importance, and also of interest to explore how negatively charged DNA can bind to a silica surface, which is also negatively charged at pH values above its isoelectric point near pH 3. We find that the two major binding mechanisms are attractive interactions between DNA phosphate and surface silanol groups and hydrophobic bonding between DNA base and silica hydrophobic region. Umbrella sampling and the weighted histogram analysis method (WHAM) are used to calculate the free energy surface for detachment of DNA from a binding configuration to a location far from the silica surface. Several factors explain why single-stranded DNA (ssDNA) has been observed to be more strongly attracted to silica than double-stranded (dsDNA): (1) ssDNA is more flexible and therefore able to maximize the number of binding interactions. (2) ssDNA has free unpaired bases to form hydrophobic attachment to silica while dsDNA has to break hydrogen bonds with base partners to get free bases. (3) The linear charge density of dsDNA is twice that of ssDNA. We devise a procedure to approximate the atomic forces between biomolecules and amorphous silica to enable large-scale biomolecule-silica simulations as reported here. PMID:25966319

  12. Male and couple fertility impairment due to HPV-DNA sperm infection: update on molecular mechanism and clinical impact--systematic review.

    PubMed

    Gizzo, Salvatore; Ferrari, Bruno; Noventa, Marco; Ferrari, Emanuele; Patrelli, Tito Silvio; Gangemi, Michele; Nardelli, Giovanni Battista

    2014-01-01

    Recent evidences identify Human Papillomavirus (HPV) sperm infection as a possible cause of male and couple infertility. It acts through different mechanisms at various steps of human conception and early gestational development. We performed a systematic review to assess the role of HPV semen infection on male and couple infertility. Analysis of available and eligible data does not permit us to fund clear evidences about clinical impact of HPV infection on fertility, although sperm parameters impairment is the most widely recognized effect. Regarding biomolecular implications, the available data are often conflicting. More studies are required to define the role of HPV sperm infection in clinical practice. The great majority of evidences are obtained by in vitro studies and this fact represents a limitation for the clinical management of HPVDNA sperm infection. Understanding the biological significance of HPV-DNA semen infection could permit us to explain most of the idiopathic male and couple infertility, leading to a better management of infertile men and a better timing for sperm banking storage before ART cycles. PMID:24783196

  13. Male and Couple Fertility Impairment due to HPV-DNA Sperm Infection: Update on Molecular Mechanism and Clinical Impact—Systematic Review

    PubMed Central

    Gizzo, Salvatore; Ferrari, Bruno; Noventa, Marco; Ferrari, Emanuele; Patrelli, Tito Silvio; Gangemi, Michele; Nardelli, Giovanni Battista

    2014-01-01

    Recent evidences identify Human Papillomavirus (HPV) sperm infection as a possible cause of male and couple infertility. It acts through different mechanisms at various steps of human conception and early gestational development. We performed a systematic review to assess the role of HPV semen infection on male and couple infertility. Analysis of available and eligible data does not permit us to fund clear evidences about clinical impact of HPV infection on fertility, although sperm parameters impairment is the most widely recognized effect. Regarding biomolecular implications, the available data are often conflicting. More studies are required to define the role of HPV sperm infection in clinical practice. The great majority of evidences are obtained by in vitro studies and this fact represents a limitation for the clinical management of HPVDNA sperm infection. Understanding the biological significance of HPV-DNA semen infection could permit us to explain most of the idiopathic male and couple infertility, leading to a better management of infertile men and a better timing for sperm banking storage before ART cycles. PMID:24783196

  14. DNA repair prognostic index modelling reveals an essential role for base excision repair in influencing clinical outcomes in ER negative and triple negative breast cancers.

    PubMed

    Abdel-Fatah, Tarek M A; Arora, Arvind; Moseley, Paul M; Perry, Christina; Rakha, Emad A; Green, Andrew R; Chan, Stephen Y T; Ellis, Ian O; Madhusudan, Srinivasan

    2015-09-01

    Stratification of oestrogen receptor (ER) negative and triple negative breast cancers (TNBCs) is urgently needed. In the current study, a cohort of 880 ER- (including 635 TNBCs) was immuno-profiled for a panel of DNA repair proteins including: Pol β, FEN1, APE1, XRCC1, SMUG1, PARP1, BRCA1, ATR, ATM, DNA-PKcs, Chk1, Chk2, p53, and TOPO2. Multivariate Cox proportional hazards models (with backward stepwise exclusion of these factors, using a criterion of p < 0.05 for retention of factors in the model) were used to identify factors that were independently associated with clinical outcomes. XRCC1 (p = 0.002), pol β (p = 0.032) FEN1 (p = 0.001) and BRCA1 (p = 0.040) levels were independently associated with poor BCSS. Subsequently, DNA repair index prognostic (DRPI) scores for breast cancer specific survival (BCSS) were calculated and two prognostic groups (DRPI-PGs) were identified. Patients in prognostic group 2 (DRPI-PG2) have higher risk of death (p < 0.001). Furthermore, in DRPI-PG2 patients, exposure to anthracycline reduced the risk of death [(HR (95% CI) = 0.79 (0.64-0.98), p = 0.032) by 21-26%. In addition, DRPI-PG2 patients have adverse clinicopathological features including higher grade, lympho-vascular invasion, Her-2 positive phenotype, compared to those in DRPI-PG1 (p < 0.01). Receiver operating characteristic (ROC) curves indicated that the DRPI outperformed the currently used prognostic factors and adding DRPI to lymph node stage significantly improved their performance as a predictor for BCSS [p < 0.00001, area under curve (AUC) = 0.70]. BER strongly influences pathogenesis of ER- and TNBCs. The DRPI accurately predicts BCSS and can also serve as a valuable prognostic and predictive tool for TNBCs. PMID:26267318

  15. Gastrointestinal Dose-Histogram Effects in the Context of Dose-Volume–Constrained Prostate Radiation Therapy: Analysis of Data From the RADAR Prostate Radiation Therapy Trial

    SciTech Connect

    Ebert, Martin A.; Foo, Kerwyn; Haworth, Annette; Gulliford, Sarah L.; Kennedy, Angel; Joseph, David J.; Denham, James W.

    2015-03-01

    Purpose: To use a high-quality multicenter trial dataset to determine dose-volume effects for gastrointestinal (GI) toxicity following radiation therapy for prostate carcinoma. Influential dose-volume histogram regions were to be determined as functions of dose, anatomical location, toxicity, and clinical endpoint. Methods and Materials: Planning datasets for 754 participants in the TROG 03.04 RADAR trial were available, with Late Effects of Normal Tissues (LENT) Subjective, Objective, Management, and Analytic (SOMA) toxicity assessment to a median of 72 months. A rank sum method was used to define dose-volume cut-points as near-continuous functions of dose to 3 GI anatomical regions, together with a comprehensive assessment of significance. Univariate and multivariate ordinal regression was used to assess the importance of cut-points at each dose. Results: Dose ranges providing significant cut-points tended to be consistent with those showing significant univariate regression odds-ratios (representing the probability of a unitary increase in toxicity grade per percent relative volume). Ranges of significant cut-points for rectal bleeding validated previously published results. Separation of the lower GI anatomy into complete anorectum, rectum, and anal canal showed the impact of mid-low doses to the anal canal on urgency and tenesmus, completeness of evacuation and stool frequency, and mid-high doses to the anorectum on bleeding and stool frequency. Derived multivariate models emphasized the importance of the high-dose region of the anorectum and rectum for rectal bleeding and mid- to low-dose regions for diarrhea and urgency and tenesmus, and low-to-mid doses to the anal canal for stool frequency, diarrhea, evacuation, and bleeding. Conclusions: Results confirm anatomical dependence of specific GI toxicities. They provide an atlas summarizing dose-histogram effects and derived constraints as functions of anatomical region, dose, toxicity, and endpoint for

  16. Detection of monoclonal integration of bovine leukemia virus proviral DNA as a malignant marker in two enzootic bovine leukosis cases with difficult clinical diagnosis

    PubMed Central

    MIURA, Saori; HORIUCHI, Noriyuki; MATSUMOTO, Kotaro; KOBAYASHI, Yoshiyasu; KAWAZU, Shin-ichiro; INOKUMA, Hisashi

    2015-01-01

    Monoclonal integration of bovine leukemia virus (BLV) proviral DNA into bovine genomes was detected in peripheral blood from two clinical cases of enzootic bovine leukosis (EBL) without enlargement of superficial lymph nodes. A BLV-specific probe hybridized with 1 to 3 EcoRI and HindIII fragments in these 2 atypical EBL cattle by Southern blotting and hybridization, as well as in 3 typical EBL cattle. The probe also hybridized to a large number of EcoRI and HindIII fragments in 5 cattle with persistent leukosis. These results suggest that the detection of monoclonal integration of BLV provirus into the host genome may serve as a marker of monoclonal proliferation and malignancy in difficult to diagnose EBL cattle. PMID:25766769

  17. Stratification of pediatric ALL by in vitro cellular responses to DNA double-strand breaks provides insight into the molecular mechanisms underlying clinical response.

    PubMed

    Marston, Eliot; Weston, Victoria; Jesson, Jennifer; Maina, Esther; McConville, Carmel; Agathanggelou, Angelo; Skowronska, Anna; Mapp, Katie; Sameith, Katrin; Powell, Judith E; Lawson, Sarah; Kearns, Pamela; Falciani, Francesco; Taylor, Malcolm; Stankovic, Tatjana

    2009-01-01

    The molecular basis of different outcomes in pediatric acute lymphoblastic leukemia (ALL) remains poorly understood. We addressed the clinical significance and mechanisms behind in vitro cellular responses to ionizing radiation (IR)-induced DNA double-strand breaks in 74 pediatric patients with ALL. We found an apoptosis-resistant response in 36% of patients characterized by failure to cleave caspase-3, -7, -9, and PARP1 by 24 hours after IR and an apoptosis-sensitive response with the cleavage of the same substrates in the remaining 64% of leukemias. Resistance to IR in vitro was associated with poor early blast clearance at day 7 or 15 and persistent minimal residual disease (MRD) at day 28 of induction treatment. Global gene expression profiling revealed abnormal up-regulation of multiple prosurvival pathways in response to IR in apoptosis-resistant leukemias and differential posttranscriptional activation of the PI3-Akt pathway was observed in representative resistant cases. Importantly, pharmacologic inhibition of selected prosurvival pathways sensitized apoptosis-resistant ALL cells to IR in vitro. We suggest that abnormal prosurvival responses to DNA damage provide one of the mechanisms of primary resistance in ALL, and that they should be considered as therapeutic targets in children with aggressive disease. PMID:18941120

  18. Prospective Study of Use of PCR Amplification and Sequencing of 16S Ribosomal DNA from Cerebrospinal Fluid for Diagnosis of Bacterial Meningitis in a Clinical Setting

    PubMed Central

    Schuurman, Tim; de Boer, Richard F.; Kooistra-Smid, Anna M. D.; van Zwet, Anton A.

    2004-01-01

    We have evaluated the use of a broad-range PCR aimed at the 16S rRNA gene in detecting bacterial meningitis in a clinical setting. To achieve a uniform DNA extraction procedure for both gram-positive and gram-negative organisms, a combination of physical disruption (bead beating) and a silica-guanidiniumthiocyanate procedure was used for nucleic acid preparation. To diminish the risk of contamination as much as possible, we chose to amplify almost the entire 16S rRNA gene. The analytical sensitivity of the assay was approximately 1 × 102 to 2 × 102 CFU/ml of cerebrospinal fluid (CSF) for both gram-negative and gram-positive bacteria. In a prospective study of 227 CSF samples, broad-range PCR proved to be superior to conventional methods in detecting bacterial meningitis when antimicrobial therapy had already started. Overall, our assay showed a sensitivity of 86%, a specificity of 97%, a positive predictive value of 80%, and a negative predictive value of 98% compared to culture. We are currently adapting the standard procedures in our laboratory for detecting bacterial meningitis; broad-range 16S ribosomal DNA PCR detection is indicated when antimicrobial therapy has already started at time of lumbar puncture or when cultures remain negative, although the suspicion of bacterial meningitis remains. PMID:14766845

  19. High-throughput, Automated Extraction of DNA and RNA from Clinical Samples using TruTip Technology on Common Liquid Handling Robots

    PubMed Central

    Holmberg, Rebecca C.; Gindlesperger, Alissa; Stokes, Tinsley; Brady, Dane; Thakore, Nitu; Belgrader, Philip; Cooney, Christopher G.; Chandler, Darrell P.

    2013-01-01

    TruTip is a simple nucleic acid extraction technology whereby a porous, monolithic binding matrix is inserted into a pipette tip. The geometry of the monolith can be adapted for specific pipette tips ranging in volume from 1.0 to 5.0 ml. The large porosity of the monolith enables viscous or complex samples to readily pass through it with minimal fluidic backpressure. Bi-directional flow maximizes residence time between the monolith and sample, and enables large sample volumes to be processed within a single TruTip. The fundamental steps, irrespective of sample volume or TruTip geometry, include cell lysis, nucleic acid binding to the inner pores of the TruTip monolith, washing away unbound sample components and lysis buffers, and eluting purified and concentrated nucleic acids into an appropriate buffer. The attributes and adaptability of TruTip are demonstrated in three automated clinical sample processing protocols using an Eppendorf epMotion 5070, Hamilton STAR and STARplus liquid handling robots, including RNA isolation from nasopharyngeal aspirate, genomic DNA isolation from whole blood, and fetal DNA extraction and enrichment from large volumes of maternal plasma (respectively). PMID:23793016

  20. Polymorphisms in the 18S rDNA gene of Cystoisospora belli and clinical features of cystoisosporosis in HIV-infected patients.

    PubMed

    Resende, Deisy V; Pedrosa, André L; Correia, Dalmo; Cabrine-Santos, Marlene; Lages-Silva, Eliane; Meira, Wendell S F; Oliveira-Silva, Márcia B

    2011-03-01

    Intraspecific variability among Cystoisospora belli isolates and its clinical implications in human cystoisosporosis have not been established. In this study, the restriction fragment length polymorphisms in a 1.8-kb amplicon of the small subunit ribosomal DNA (SSU rDNA) of the parasite was investigated in 20 C. belli-positive stool samples obtained from 15 HIV-infected patients. Diarrheic syndrome was observed in all patients with cystoisosporosis and the number of diarrheic episodes per patient during hospitalization ranged from 1 to 26 (mean of 9.64 ± 9.30), with a mean duration of 2 to 12 days (mean of 5.90 ± 3 days). Three restriction profiles (RF) were generated with MboII digestion, which were named RFI, RFII, and RFIII. Two isolates obtained from a patient with extraintestinal cystoisosporosis showed distinct restriction profiles with MboII. This study demonstrates that patients can be infected with different C. belli genotypes, and this information may be useful for identifying new C. belli genotypes infecting humans. PMID:20967461

  1. TaBoo SeArch Algorithm with a Modified Inverse Histogram for Reproducing Biologically Relevant Rare Events of Proteins.

    PubMed

    Harada, Ryuhei; Takano, Yu; Shigeta, Yasuteru

    2016-05-10

    The TaBoo SeArch (TBSA) algorithm [ Harada et al. J. Comput. Chem. 2015 , 36 , 763 - 772 and Harada et al. Chem. Phys. Lett. 2015 , 630 , 68 - 75 ] was recently proposed as an enhanced conformational sampling method for reproducing biologically relevant rare events of a given protein. In TBSA, an inverse histogram of the original distribution, mapped onto a set of reaction coordinates, is constructed from trajectories obtained by multiple short-time molecular dynamics (MD) simulations. Rarely occurring states of a given protein are statistically selected as new initial states based on the inverse histogram, and resampling is performed by restarting the MD simulations from the new initial states to promote the conformational transition. In this process, the definition of the inverse histogram, which characterizes the rarely occurring states, is crucial for the efficiency of TBSA. In this study, we propose a simple modification of the inverse histogram to further accelerate the convergence of TBSA. As demonstrations of the modified TBSA, we applied it to (a) hydrogen bonding rearrangements of Met-enkephalin, (b) large-amplitude domain motions of Glutamine-Binding Protein, and (c) folding processes of the B domain of Staphylococcus aureus Protein A. All demonstrations numerically proved that the modified TBSA reproduced these biologically relevant rare events with nanosecond-order simulation times, although a set of microsecond-order, canonical MD simulations failed to reproduce the rare events, indicating the high efficiency of the modified TBSA. PMID:27070761

  2. Students' Misconceptions in Interpreting Center and Variability of Data Represented via Histograms and Stem-and-Leaf Plots

    ERIC Educational Resources Information Center

    Cooper, Linda L.; Shore, Felice S.

    2008-01-01

    This paper identifies and discusses misconceptions that students have in making judgments of center and variability when data are presented graphically. An assessment addressing interpreting center and variability in histograms and stem-and-leaf plots was administered to, and follow-up interviews were conducted with, undergraduates enrolled in…

  3. Estimation of the content of fat and parenchyma in breast tissue using MRI T1 histograms and phantoms.

    PubMed

    Boston, Raymond C; Schnall, Mitchell D; Englander, Sarah A; Landis, J Richard; Moate, Peter J

    2005-05-01

    Mammographic breast density has been correlated with breast cancer risk. Estimation of the volumetric composition of breast tissue using three-dimensional MRI has been proposed, but accuracy depends upon the estimation methods employed. The use of segmentation based on T1 relaxation rates allows quantitative estimates of fat and parenchyma volume, but is limited by partial volume effects. An investigation employing phantom breast tissue composed of various combinations of chicken breast (to represent parenchyma) and cooking fats was carried out to elucidate the factors that influence MRI T1 histograms. Using the phantoms, T1 histograms and their known fat and parenchyma composition, a logistic distribution function was derived to describe the apportioning of the T1 histogram to fat and parenchyma. This function and T1 histograms were then used to predict the fat and parenchyma content of breasts from 14 women. Using this method, the composition of the breast tissue in the study population was as follows: fat 69.9+/-22.9% and parenchyma 30.1+/-22.9%. PMID:15919606

  4. Studying the time histogram of a terrestrial electron beam detected from the opposite hemisphere of its associated TGF

    NASA Astrophysics Data System (ADS)

    Sarria, D.; Blelly, P.-L.; Briggs, M. S.; Forme, F.

    2016-05-01

    Terrestrial gamma-ray flashes are bursts of X/gamma photons, correlated to thunderstorms. By interacting with the atmosphere, the photons produce a substantial number of electrons and positrons. Some of these reach a sufficiently high altitude that their interactions with the atmosphere become negligible, and they are then guided by geomagnetic field lines, forming a Terrestrial Electron Beam. On 9 December 2009, the Gamma-Ray Burst Monitor (GBM) instrument on board the Fermi Space Telescope made a particularly interesting measurement of such an event. To study this type of event in detail, we perform Monte-Carlo simulations and focus on the resulting time histograms. In agreement with previous work, we show that the histogram measured by Fermi GBM is reproducible from a simulation. We then show that the time histogram resulting from this simulation is only weakly dependent on the production altitude, duration, beaming angle, and spectral shape of the associated terrestrial gamma-ray flash. Finally, we show that the time histogram can be decomposed into three populations of leptons, coming from the opposite hemisphere, and mirroring back to the satellite with or without interacting with the atmosphere, and that these populations can be clearly distinguished by their pitch angles.

  5. Dynamic Contrast-enhanced MR Imaging in Renal Cell Carcinoma: Reproducibility of Histogram Analysis on Pharmacokinetic Parameters

    PubMed Central

    Wang, Hai-yi; Su, Zi-hua; Xu, Xiao; Sun, Zhi-peng; Duan, Fei-xue; Song, Yuan-yuan; Li, Lu; Wang, Ying-wei; Ma, Xin; Guo, Ai-tao; Ma, Lin; Ye, Hui-yi

    2016-01-01

    Pharmacokinetic parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) have been increasingly used to evaluate the permeability of tumor vessel. Histogram metrics are a recognized promising method of quantitative MR imaging that has been recently introduced in analysis of DCE-MRI pharmacokinetic parameters in oncology due to tumor heterogeneity. In this study, 21 patients with renal cell carcinoma (RCC) underwent paired DCE-MRI studies on a 3.0 T MR system. Extended Tofts model and population-based arterial input function were used to calculate kinetic parameters of RCC tumors. Mean value and histogram metrics (Mode, Skewness and Kurtosis) of each pharmacokinetic parameter were generated automatically using ImageJ software. Intra- and inter-observer reproducibility and scan–rescan reproducibility were evaluated using intra-class correlation coefficients (ICCs) and coefficient of variation (CoV). Our results demonstrated that the histogram method (Mode, Skewness and Kurtosis) was not superior to the conventional Mean value method in reproducibility evaluation on DCE-MRI pharmacokinetic parameters (K trans & Ve) in renal cell carcinoma, especially for Skewness and Kurtosis which showed lower intra-, inter-observer and scan-rescan reproducibility than Mean value. Our findings suggest that additional studies are necessary before wide incorporation of histogram metrics in quantitative analysis of DCE-MRI pharmacokinetic parameters. PMID:27380733

  6. Multilevel image thresholding based on 2D histogram and maximum Tsallis entropy--a differential evolution approach.

    PubMed

    Sarkar, Soham; Das, Swagatam

    2013-12-01

    Multilevel thresholding amounts to segmenting a gray-level image into several distinct regions. This paper presents a 2D histogram based multilevel thresholding approach to improve the separation between objects. Recent studies indicate that the results obtained with 2D histogram oriented approaches are superior to those obtained with 1D histogram based techniques in the context of bi-level thresholding. Here, a method to incorporate 2D histogram related information for generalized multilevel thresholding is proposed using the maximum Tsallis entropy. Differential evolution (DE), a simple yet efficient evolutionary algorithm of current interest, is employed to improve the computational efficiency of the proposed method. The performance of DE is investigated extensively through comparison with other well-known nature inspired global optimization techniques such as genetic algorithm, particle swarm optimization, artificial bee colony, and simulated annealing. In addition, the outcome of the proposed method is evaluated using a well known benchmark--the Berkley segmentation data set (BSDS300) with 300 distinct images. PMID:23955760

  7. Dynamic Contrast-enhanced MR Imaging in Renal Cell Carcinoma: Reproducibility of Histogram Analysis on Pharmacokinetic Parameters.

    PubMed

    Wang, Hai-Yi; Su, Zi-Hua; Xu, Xiao; Sun, Zhi-Peng; Duan, Fei-Xue; Song, Yuan-Yuan; Li, Lu; Wang, Ying-Wei; Ma, Xin; Guo, Ai-Tao; Ma, Lin; Ye, Hui-Yi

    2016-01-01

    Pharmacokinetic parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) have been increasingly used to evaluate the permeability of tumor vessel. Histogram metrics are a recognized promising method of quantitative MR imaging that has been recently introduced in analysis of DCE-MRI pharmacokinetic parameters in oncology due to tumor heterogeneity. In this study, 21 patients with renal cell carcinoma (RCC) underwent paired DCE-MRI studies on a 3.0 T MR system. Extended Tofts model and population-based arterial input function were used to calculate kinetic parameters of RCC tumors. Mean value and histogram metrics (Mode, Skewness and Kurtosis) of each pharmacokinetic parameter were generated automatically using ImageJ software. Intra- and inter-observer reproducibility and scan-rescan reproducibility were evaluated using intra-class correlation coefficients (ICCs) and coefficient of variation (CoV). Our results demonstrated that the histogram method (Mode, Skewness and Kurtosis) was not superior to the conventional Mean value method in reproducibility evaluation on DCE-MRI pharmacokinetic parameters (K( trans) &Ve) in renal cell carcinoma, especially for Skewness and Kurtosis which showed lower intra-, inter-observer and scan-rescan reproducibility than Mean value. Our findings suggest that additional studies are necessary before wide incorporation of histogram metrics in quantitative analysis of DCE-MRI pharmacokinetic parameters. PMID:27380733

  8. Analysis of Mutations in the Gene Encoding Cytomegalovirus DNA Polymerase in a Phase 2 Clinical Trial of Brincidofovir Prophylaxis

    PubMed Central

    Lanier, E. Randall; Foster, Scott; Brundage, Tom; Chou, Sunwen; Prichard, Mark N.; Kleiboeker, Steven; Wilson, Chad; Colville, Donella; Mommeja-Marin, Herve

    2016-01-01

    Brincidofovir is an oral antiviral in development for prevention of cytomegalovirus disease. Cytomegalovirus genotyping results from a phase 2 trial comparing brincidofovir to placebo for prophylaxis against cytomegalovirus infection in hematopoietic cell transplant recipients provided initial data on the clinical resistance profile for brincidofovir. In this study, no known resistance-associated mutations were detected in brincidofovir-treated subjects; identified genotypic substitutions did not confer resistance to cytomegalovirus antivirals in vitro, suggesting that these changes represent polymorphisms unrelated to brincidofovir resistance. Lack of evidence for genotypic resistance during prophylaxis suggests that first-line use of brincidofovir for prevention of cytomegalovirus infection may preserve downstream options for patients. PMID:26941282

  9. Analysis of Mutations in the Gene Encoding Cytomegalovirus DNA Polymerase in a Phase 2 Clinical Trial of Brincidofovir Prophylaxis.

    PubMed

    Lanier, E Randall; Foster, Scott; Brundage, Tom; Chou, Sunwen; Prichard, Mark N; Kleiboeker, Steven; Wilson, Chad; Colville, Donella; Mommeja-Marin, Herve

    2016-07-01

    Brincidofovir is an oral antiviral in development for prevention of cytomegalovirus disease. Cytomegalovirus genotyping results from a phase 2 trial comparing brincidofovir to placebo for prophylaxis against cytomegalovirus infection in hematopoietic cell transplant recipients provided initial data on the clinical resistance profile for brincidofovir. In this study, no known resistance-associated mutations were detected in brincidofovir-treated subjects; identified genotypic substitutions did not confer resistance to cytomegalovirus antivirals in vitro, suggesting that these changes represent polymorphisms unrelated to brincidofovir resistance. Lack of evidence for genotypic resistance during prophylaxis suggests that first-line use of brincidofovir for prevention of cytomegalovirus infection may preserve downstream options for patients. PMID:26941282

  10. Reliable and sensitive detection of fragile X (expanded) alleles in clinical prenatal DNA samples with a fast turnaround time.

    PubMed

    Seneca, Sara; Lissens, Willy; Endels, Kristof; Caljon, Ben; Bonduelle, Maryse; Keymolen, Kathleen; De Rademaeker, Marjan; Ullmann, Urielle; Haentjens, Patrick; Van Berkel, Kim; Van Dooren, Sonia

    2012-11-01

    This study evaluated a large set of blinded, previously analyzed prenatal DNA samples with a novel, CGG triplet-repeat primed (TP)-PCR assay (Amplidex FMR1 PCR Kit; Asuragen, Austin, TX). This cohort of 67 fetal DNAs contained 18 full mutations (270 to 1100 repeats, including 1 mosaic), 12 premutations (59 to 150 repeats), 9 intermediate mutations (54 to 58 repeats), and 28 normal samples (17 to 50 repeats, including 3 homozygous female samples). TP-PCR accurately identified FMR1 genotypes, ranging from normal to full- mutation alleles, with a 100% specificity (95% CI, 85.0% to 100%) and a 97.4% sensitivity (95% CI, 84.9% to 99.9%) in comparison with Southern blot analysis results. Exact sizing was possible for a spectrum of normal, intermediate, and premutation (up to 150 repeats) alleles, but CGG repeat numbers >200 are only identified as full mutations. All homozygous alleles were correctly resolved. The assay is also able to reproducibly detect a 2.5% premutation and a 3% full-mutation mosaicism in a normal male background, but a large premutation in a full male mutation background was masked when the amount of the latter was >5%. Implementation of this TP-PCR will significantly reduce reflex testing using Southern blot analyses. Additional testing with methylation-informative techniques might still be needed for a few cases with (large) premutations or full mutations. PMID:22921311

  11. Automated geomorphometric classification of landforms in Transdanubian Region (Pannonian Basin) based on local slope histograms

    NASA Astrophysics Data System (ADS)

    Székely, Balázs; Koma, Zsófia; Csorba, Kristóf; Ferenc Morovics, József

    2014-05-01

    The Transdanubian Region is a typically hilly, geologically manifold area of the Pannonian Basin. It is composed primarily of Permo-Mesozoic carbonates and siliciclastic sediments, however Pannonian sedimentary units and young volcanic forms are also characteristic, such as those in the Bakony-Balaton Highland Volcanic Field. The geological diversity is reflected in the geomorphological setting: beside of the classic eroding volcanic edifices, carbonate plateaus, medium-relief, gently hilly, slowly eroding landforms are also frequent in the geomorphic mosaic of the area. Geomorphometric techniques are suitable to analyse and separate the various geomorphic units mosaicked and, in some cases, affected by (sub-)recent tectonic geomorphic processes. In our project we applied automated classification of local slope angle histograms derived of a 10-meter nominal resolution digital terrain model (DTM). Slope angle histrograms within a rectangular moving window of various sizes have been calculated in numerous experiments. The histograms then served as a multichannel input of for a k-means classification to achieve a geologically-geomorphologically sound categorization of the area. The experiments show good results in separating the very basic landforms, defined landscape boundaries can be reconstructed with high accuracy in case of larger window sizes (e.g. 5 km) and low number of categories. If the window size is smaller and the number of classes is higher, the tectonic geomorphic features are more prominently recognized, however often at the price of the clear separation boundaries: in these cases the horizontal change in the composition of various clusters matches the boundaries of the geological units. Volcanic forms are typically also put into some definite classes, however the flat plateaus of some volcanic edifices fall into another category also recognized in the experiments. In summary we can conclude that the area is suitable for such analyses, many

  12. Normal-reciprocal error models for quantitative ERT in permafrost environments: bin analysis versus histogram analysis

    NASA Astrophysics Data System (ADS)

    Verleysdonk, Sarah; Flores-Orozco, Adrian; Krautblatter, Michael; Kemna, Andreas

    2010-05-01

    Electrical resistivity tomography (ERT) has been used for the monitoring of permafrost-affected rock walls for some years now. To further enhance the interpretation of ERT measurements a deeper insight into error sources and the influence of error model parameters on the imaging results is necessary. Here, we present the effect of different statistical schemes for the determination of error parameters from the discrepancies between normal and reciprocal measurements - bin analysis and histogram analysis - using a smoothness-constrained inversion code (CRTomo) with an incorporated appropriate error model. The study site is located in galleries adjacent to the Zugspitze North Face (2800 m a.s.l.) at the border between Austria and Germany. A 20 m * 40 m rock permafrost body and its surroundings have been monitored along permanently installed transects - with electrode spacings of 1.5 m and 4.6 m - from 2007 to 2009. For data acquisition, a conventional Wenner survey was conducted as this array has proven to be the most robust array in frozen rock walls. Normal and reciprocal data were collected directly one after another to ensure identical conditions. The ERT inversion results depend strongly on the chosen parameters of the employed error model, i.e., the absolute resistance error and the relative resistance error. These parameters were derived (1) for large normal/reciprocal data sets by means of bin analyses and (2) for small normal/reciprocal data sets by means of histogram analyses. Error parameters were calculated independently for each data set of a monthly monitoring sequence to avoid the creation of artefacts (over-fitting of the data) or unnecessary loss of contrast (under-fitting of the data) in the images. The inversion results are assessed with respect to (1) raw data quality as described by the error model parameters, (2) validation via available (rock) temperature data and (3) the interpretation of the images from a geophysical as well as a

  13. Characterization of polybacterial clinical samples using a set of group-specific broad-range primers targeting the 16S rRNA gene followed by DNA sequencing and RipSeq analysis

    PubMed Central

    Lekang, Katrine; Langeland, Nina; Wiker, Harald G.

    2011-01-01

    The standard use of a single universal broad-range PCR in direct 16S rDNA sequencing from polybacterial samples leaves the minor constituents at risk of remaining undetected because all bacterial DNA will be competing for the same reagents. In this article we introduce a set of three broad-range group-specific 16S rDNA PCRs that together cover the clinically relevant bacteria and apply them in the investigation of 25 polybacterial clinical samples. Mixed DNA chromatograms from samples containing more than one species per primer group were analysed using RipSeq Mixed (iSentio, Norway), a web-based application for the interpretation of chromatograms containing up to three different species. The group-specific PCRs reduced complexity in the resulting DNA chromatograms and made the assay more sensitive in situations with unequal species concentrations. Together this allowed for identification of a significantly higher number of bacterial species than did standard direct sequencing with a single universal primer pair and RipSeq analysis (95 vs 51). The method could improve microbiological diagnostics for important groups of patients and can be established in any laboratory with experience in direct 16S rDNA sequencing. PMID:21436365

  14. Computationally efficient multidimensional analysis of complex flow cytometry data using second order polynomial histograms.

    PubMed

    Zaunders, John; Jing, Junmei; Leipold, Michael; Maecker, Holden; Kelleher, Anthony D; Koch, Inge

    2016-01-01

    Many methods have been described for automated clustering analysis of complex flow cytometry data, but so far the goal to efficiently estimate multivariate densities and their modes for a moderate number of dimensions and potentially millions of data points has not been attained. We have devised a novel approach to describing modes using second order polynomial histogram estimators (SOPHE). The method divides the data into multivariate bins and determines the shape of the data in each bin based on second order polynomials, which is an efficient computation. These calculations yield local maxima and allow joining of adjacent bins to identify clusters. The use of second order polynomials also optimally uses wide bins, such that in most cases each parameter (dimension) need only be divided into 4-8 bins, again reducing computational load. We have validated this method using defined mixtures of up to 17 fluorescent beads in 16 dimensions, correctly identifying all populations in data files of 100,000 beads in <10 s, on a standard laptop. The method also correctly clustered granulocytes, lymphocytes, including standard T, B, and NK cell subsets, and monocytes in 9-color stained peripheral blood, within seconds. SOPHE successfully clustered up to 36 subsets of memory CD4 T cells using differentiation and trafficking markers, in 14-color flow analysis, and up to 65 subpopulations of PBMC in 33-dimensional CyTOF data, showing its usefulness in discovery research. SOPHE has the potential to greatly increase efficiency of analysing complex mixtures of cells in higher dimensions. PMID:26097104

  15. A generic shape/texture descriptor over multiscale edge field: 2-D walking ant histogram.

    PubMed

    Kiranyaz, Serkan; Ferreira, Miguel; Gabbouj, Moncef

    2008-03-01

    A novel shape descriptor, which can be extracted from the major object edges automatically and used for the multimedia content-based retrieval in multimedia databases, is presented. By adopting a multiscale approach over the edge field where the scale represents the amount of simplification, the most relevant edge segments, referred to as subsegments, which eventually represent the major object boundaries, are extracted from a scale-map. Similar to the process of a walking ant with a limited line of sight over the boundary of a particular object, we traverse through each subsegment and describe a certain line of sight, whether it is a continuous branch or a corner, using individual 2-D histograms. Furthermore, the proposed method can also be tuned to be an efficient texture descriptor, which achieves a superior performance especially for directional textures. Finally, integrating the whole process as feature extraction module into MUVIS framework allows us to test the mutual performance of the proposed shape descriptor in the context of multimedia indexing and retrieval. PMID:18270126

  16. Medical image classification using spatial adjacent histogram based on adaptive local binary patterns.

    PubMed

    Liu, Dong; Wang, Shengsheng; Huang, Dezhi; Deng, Gang; Zeng, Fantao; Chen, Huiling

    2016-05-01

    Medical image recognition is an important task in both computer vision and computational biology. In the field of medical image classification, representing an image based on local binary patterns (LBP) descriptor has become popular. However, most existing LBP-based methods encode the binary patterns in a fixed neighborhood radius and ignore the spatial relationships among local patterns. The ignoring of the spatial relationships in the LBP will cause a poor performance in the process of capturing discriminative features for complex samples, such as medical images obtained by microscope. To address this problem, in this paper we propose a novel method to improve local binary patterns by assigning an adaptive neighborhood radius for each pixel. Based on these adaptive local binary patterns, we further propose a spatial adjacent histogram strategy to encode the micro-structures for image representation. An extensive set of evaluations are performed on four medical datasets which show that the proposed method significantly improves standard LBP and compares favorably with several other prevailing approaches. PMID:27058283

  17. A multiresolution approach to image enhancement via histogram shaping and adaptive Wiener filtering

    NASA Astrophysics Data System (ADS)

    Pace, T.; Manville, D.; Lee, H.; Cloud, G.; Puritz, J.

    2008-04-01

    It is critical in military applications to be able to extract features in imagery that may be of interest to the viewer at any time of the day or night. Infrared (IR) imagery is ideally suited for producing these types of images. However, even under the best of circumstances, the traditional approach of applying a global automatic gain control (AGC) to the digital image may not provide the user with local area details that may be of interest. Processing the imagery locally can enhance additional features and characteristics in the image which provide the viewer with an improved understanding of the scene being observed. This paper describes a multi-resolution pyramid approach for decomposing an image, enhancing its contrast by remapping the histograms to desired pdfs, filtering them and recombining them to create an output image with much more visible detail than the input image. The technique improves the local area image contrast in light and dark areas providing the warfighter with significantly improved situational awareness.

  18. Fast and fully automatic phalanx segmentation using a grayscale-histogram morphology algorithm

    NASA Astrophysics Data System (ADS)

    Hsieh, Chi-Wen; Liu, Tzu-Chiang; Jong, Tai-Lang; Chen, Chih-Yen; Tiu, Chui-Mei; Chan, Din-Yuen

    2011-08-01

    Bone age assessment is a common radiological examination used in pediatrics to diagnose the discrepancy between the skeletal and chronological age of a child; therefore, it is beneficial to develop a computer-based bone age assessment to help junior pediatricians estimate bone age easily. Unfortunately, the phalanx on radiograms is not easily separated from the background and soft tissue. Therefore, we proposed a new method, called the grayscale-histogram morphology algorithm, to segment the phalanges fast and precisely. The algorithm includes three parts: a tri-stage sieve algorithm used to eliminate the background of hand radiograms, a centroid-edge dual scanning algorithm to frame the phalanx region, and finally a segmentation algorithm based on disk traverse-subtraction filter to segment the phalanx. Moreover, two more segmentation methods: adaptive two-mean and adaptive two-mean clustering were performed, and their results were compared with the segmentation algorithm based on disk traverse-subtraction filter using five indices comprising misclassification error, relative foreground area error, modified Hausdorff distances, edge mismatch, and region nonuniformity. In addition, the CPU time of the three segmentation methods was discussed. The result showed that our method had a better performance than the other two methods. Furthermore, satisfactory segmentation results were obtained with a low standard error.

  19. Fast and efficient search for MPEG-4 video using adjacent pixel intensity difference quantization histogram feature

    NASA Astrophysics Data System (ADS)

    Lee, Feifei; Kotani, Koji; Chen, Qiu; Ohmi, Tadahiro

    2010-02-01

    In this paper, a fast search algorithm for MPEG-4 video clips from video database is proposed. An adjacent pixel intensity difference quantization (APIDQ) histogram is utilized as the feature vector of VOP (video object plane), which had been reliably applied to human face recognition previously. Instead of fully decompressed video sequence, partially decoded data, namely DC sequence of the video object are extracted from the video sequence. Combined with active search, a temporal pruning algorithm, fast and robust video search can be realized. The proposed search algorithm has been evaluated by total 15 hours of video contained of TV programs such as drama, talk, news, etc. to search for given 200 MPEG-4 video clips which each length is 15 seconds. Experimental results show the proposed algorithm can detect the similar video clip in merely 80ms, and Equal Error Rate (ERR) of 2 % in drama and news categories are achieved, which are more accurately and robust than conventional fast video search algorithm.

  20. 3D/2D image registration using weighted histogram of gradient directions

    NASA Astrophysics Data System (ADS)

    Ghafurian, Soheil; Hacihaliloglu, Ilker; Metaxas, Dimitris N.; Tan, Virak; Li, Kang

    2015-03-01

    Three dimensional (3D) to two dimensional (2D) image registration is crucial in many medical applications such as image-guided evaluation of musculoskeletal disorders. One of the key problems is to estimate the 3D CT- reconstructed bone model positions (translation and rotation) which maximize the similarity between the digitally reconstructed radiographs (DRRs) and the 2D fluoroscopic images using a registration method. This problem is computational-intensive due to a large search space and the complicated DRR generation process. Also, finding a similarity measure which converges to the global optimum instead of local optima adds to the challenge. To circumvent these issues, most existing registration methods need a manual initialization, which requires user interaction and is prone to human error. In this paper, we introduce a novel feature-based registration method using the weighted histogram of gradient directions of images. This method simplifies the computation by searching the parameter space (rotation and translation) sequentially rather than simultaneously. In our numeric simulation experiments, the proposed registration algorithm was able to achieve sub-millimeter and sub-degree accuracies. Moreover, our method is robust to the initial guess. It can tolerate up to +/-90°rotation offset from the global optimal solution, which minimizes the need for human interaction to initialize the algorithm.

  1. Computing Spatial Distance Histograms for Large Scientific Datasets On-the-Fly

    PubMed Central

    Kumar, Anand; Grupcev, Vladimir; Yuan, Yongke; Huang, Jin; Shen, Gang

    2014-01-01

    This paper focuses on an important query in scientific simulation data analysis: the Spatial Distance Histogram (SDH). The computation time of an SDH query using brute force method is quadratic. Often, such queries are executed continuously over certain time periods, increasing the computation time. We propose highly efficient approximate algorithm to compute SDH over consecutive time periods with provable error bounds. The key idea of our algorithm is to derive statistical distribution of distances from the spatial and temporal characteristics of particles. Upon organizing the data into a Quad-tree based structure, the spatiotemporal characteristics of particles in each node of the tree are acquired to determine the particles’ spatial distribution as well as their temporal locality in consecutive time periods. We report our efforts in implementing and optimizing the above algorithm in Graphics Processing Units (GPUs) as means to further improve the efficiency. The accuracy and efficiency of the proposed algorithm is backed by mathematical analysis and results of extensive experiments using data generated from real simulation studies. PMID:25264418

  2. Nonlinear histogram binning for quantitative analysis of lung tissue fibrosis in high-resolution CT data

    NASA Astrophysics Data System (ADS)

    Zavaletta, Vanessa A.; Bartholmai, Brian J.; Robb, Richard A.

    2007-03-01

    Diffuse lung diseases, such as idiopathic pulmonary fibrosis (IPF), can be characterized and quantified by analysis of volumetric high resolution CT scans of the lungs. These data sets typically have dimensions of 512 x 512 x 400. It is too subjective and labor intensive for a radiologist to analyze each slice and quantify regional abnormalities manually. Thus, computer aided techniques are necessary, particularly texture analysis techniques which classify various lung tissue types. Second and higher order statistics which relate the spatial variation of the intensity values are good discriminatory features for various textures. The intensity values in lung CT scans range between [-1024, 1024]. Calculation of second order statistics on this range is too computationally intensive so the data is typically binned between 16 or 32 gray levels. There are more effective ways of binning the gray level range to improve classification. An optimal and very efficient way to nonlinearly bin the histogram is to use a dynamic programming algorithm. The objective of this paper is to show that nonlinear binning using dynamic programming is computationally efficient and improves the discriminatory power of the second and higher order statistics for more accurate quantification of diffuse lung disease.

  3. Facial expression recognition and histograms of oriented gradients: a comprehensive study.

    PubMed

    Carcagnì, Pierluigi; Del Coco, Marco; Leo, Marco; Distante, Cosimo

    2015-01-01

    Automatic facial expression recognition (FER) is a topic of growing interest mainly due to the rapid spread of assistive technology applications, as human-robot interaction, where a robust emotional awareness is a key point to best accomplish the assistive task. This paper proposes a comprehensive study on the application of histogram of oriented gradients (HOG) descriptor in the FER problem, highlighting as this powerful technique could be effectively exploited for this purpose. In particular, this paper highlights that a proper set of the HOG parameters can make this descriptor one of the most suitable to characterize facial expression peculiarities. A large experimental session, that can be divided into three different phases, was carried out exploiting a consolidated algorithmic pipeline. The first experimental phase was aimed at proving the suitability of the HOG descriptor to characterize facial expression traits and, to do this, a successful comparison with most commonly used FER frameworks was carried out. In the second experimental phase, different publicly available facial datasets were used to test the system on images acquired in different conditions (e.g. image resolution, lighting conditions, etc.). As a final phase, a test on continuous data streams was carried out on-line in order to validate the system in real-world operating conditions that simulated a real-time human-machine interaction. PMID:26543779

  4. Visualization of boundaries in CT volumetric data sets using dynamic M-|∇f| histogram.

    PubMed

    Li, Lu; Peng, Hu; Chen, Xun; Cheng, Juan; Gao, Dayong

    2016-01-01

    Direct volume rendering is widely used for three-dimensional medical data visualization such as computed tomography and magnetic resonance imaging. Distinct visualization of boundaries is able to provide valuable and insightful information in many medical applications. However, it is conventionally challenging to detect boundaries reliably due to limitations of the transfer function design. Meanwhile, the interactive strategy is complicated for new users or even experts. In this paper, we build a generalized boundary model contaminated by noise and prove boundary middle value (M) has a good statistical property. Based on the model we propose a user-friendly strategy for the boundary extraction and transfer function design, using M, boundary height (Δh), and gradient magnitude (|∇f|). In fact, it is a dynamic iterative process. First, potential boundaries are sorted orderly from high to low according to the value of their height. Then, users iteratively extract the boundary with the highest value of Δh in a newly defined domain, where different boundaries are transformed to disjoint vertical bars using M-|∇f| histogram. In this case, the chance of misclassification among different boundaries decreases. PMID:26649763

  5. Sequencer-Based Capillary Gel Electrophoresis (SCGE) Targeting the rDNA Internal Transcribed Spacer (ITS) Regions for Accurate Identification of Clinically Important Yeast Species

    PubMed Central

    Chen, Sharon C.-A.; Wang, He; Zhang, Li; Fan, Xin; Xu, Zhi-Peng; Cheng, Jing-Wei; Kong, Fanrong; Zhao, Yu-Pei; Xu, Ying-Chun

    2016-01-01

    Accurate species identification of Candida, Cryptococcus, Trichosporon and other yeast pathogens is important for clinical management. In the present study, we developed and evaluated a yeast species identification scheme by determining the rDNA internal transcribed spacer (ITS) region length types (LTs) using a sequencer-based capillary gel electrophoresis (SCGE) approach. A total of 156 yeast isolates encompassing 32 species were first used to establish a reference SCGE ITS LT database. Evaluation of the ITS LT database was then performed on (i) a separate set of (n = 97) clinical isolates by SCGE, and (ii) 41 isolates of 41 additional yeast species from GenBank by in silico analysis. Of 156 isolates used to build the reference database, 41 ITS LTs were identified, which correctly identified 29 of the 32 (90.6%) species, with the exception of Trichosporon asahii, Trichosporon japonicum and Trichosporon asteroides. In addition, eight of the 32 species revealed different electropherograms and were subtyped into 2–3 different ITS LTs each. Of the 97 test isolates used to evaluate the ITS LT scheme, 96 (99.0%) were correctly identified to species level, with the remaining isolate having a novel ITS LT. Of the additional 41 isolates for in silico analysis, none was misidentified by the ITS LT database except for Trichosporon mucoides whose ITS LT profile was identical to that of Trichosporon dermatis. In conclusion, yeast identification by the present SCGE ITS LT assay is a fast, reproducible and accurate alternative for the identification of clinically important yeasts with the exception of Trichosporon species. PMID:27105313

  6. WE-A-17A-12: The Influence of Eye Plaque Design On Dose Distributions and Dose- Volume Histograms

    SciTech Connect

    Aryal, P; Molloy, JA; Rivard, MJ

    2014-06-15

    Purpose: To investigate the effect of slot design of the model EP917 plaque on dose distributions and dose-volume histograms (DVHs). Methods: The dimensions and orientation of the slots in EP917 plaques were measured. In the MCNP5 radiation simulation geometry, dose distributions on orthogonal planes and DVHs for a tumor and sclera were generated for comparisons. 27 slot designs and 13 plaques were evaluated and compared with the published literature and the Plaque Simulator clinical treatment planning system. Results: The dosimetric effect of the gold backing composition and mass density was < 3%. Slot depth, width, and length changed the central axis (CAX) dose distributions by < 1% per 0.1 mm in design variation. Seed shifts in the slot towards the eye and shifts of the {sup 125} I-coated Ag rod within the capsule had the greatest impact on CAX dose distribution, increasing by 14%, 9%, 4%, and 2.5% at 1, 2, 5, and 10 mm, respectively, from the inner sclera. Along the CAX, dose from the full plaque geometry using the measured slot design was 3.4% ± 2.3% higher than the manufacturer-provided geometry. D{sub 10} for the simulated tumor, inner sclera, and outer sclera for the measured plaque was also higher, but 9%, 10%, and 20%, respectively. In comparison to the measured plaque design, a theoretical plaque having narrow and deep slots delivered 30%, 37%, and 62% lower D{sub 10} doses to the tumor, inner sclera, and outer sclera, respectively. CAX doses at −1, 0, 1, and 2 mm were also lower by a factor of 2.6, 1.4, 1.23, and 1.13, respectively. Conclusion: The study identified substantial sensitivity of the EP917 plaque dose distributions to slot design. However, it did not identify substantial dosimetric variations based on radionuclide choice ({sup 125}I, {sup 103}Pd, or {sup 131}Cs). COMS plaques provided lower scleral doses with similar tumor dose coverage.

  7. Plasmid DNA immunization with Trypanosoma cruzi genes induces cardiac and clinical protection against Chagas disease in the canine model

    PubMed Central

    2012-01-01

    The only existing preventive measure against American trypanosomosis, or Chagas disease, is the control of the transmitting insect, which has only been effective in a few South American regions. Currently, there is no vaccine available to prevent this disease. Here, we present the clinical and cardiac levels of protection induced by expression to Trypanosoma cruzi genes encoding the TcSP and TcSSP4 proteins in the canine model. Physical examination, diagnostic chagasic serology, and serial electrocardiograms were performed before and after immunization, as well as after experimental infection. We found that immunization with recombinant plasmids prevented hyperthermia in the acute phase of experimental infection and produced lymphadenomegaly as an immunological response against the parasite and additionally prevented heart rate elevation (tachycardia) in the acute and/or chronic stages of infection. Immunization with T. cruzi genes encoding the TcSP and TcSSP4 antigens diminished the quality and quantity of the electrocardiographic abnormalities, thereby avoiding progression to more severe developments such as right bundle branch block or ventricular premature complexes in a greater number of dogs. PMID:23148870

  8. Plasmid DNA immunization with Trypanosoma cruzi genes induces cardiac and clinical protection against Chagas disease in the canine model.

    PubMed

    Rodríguez-Morales, Olivia; Pérez-Leyva, M Magdalena; Ballinas-Verdugo, Martha A; Carrillo-Sánchez, Silvia C; Rosales-Encina, J Luis; Alejandre-Aguilar, Ricardo; Reyes, Pedro A; Arce-Fonseca, Minerva

    2012-01-01

    The only existing preventive measure against American trypanosomosis, or Chagas disease, is the control of the transmitting insect, which has only been effective in a few South American regions. Currently, there is no vaccine available to prevent this disease. Here, we present the clinical and cardiac levels of protection induced by expression to Trypanosoma cruzi genes encoding the TcSP and TcSSP4 proteins in the canine model. Physical examination, diagnostic chagasic serology, and serial electrocardiograms were performed before and after immunization, as well as after experimental infection. We found that immunization with recombinant plasmids prevented hyperthermia in the acute phase of experimental infection and produced lymphadenomegaly as an immunological response against the parasite and additionally prevented heart rate elevation (tachycardia) in the acute and/or chronic stages of infection. Immunization with T. cruzi genes encoding the TcSP and TcSSP4 antigens diminished the quality and quantity of the electrocardiographic abnormalities, thereby avoiding progression to more severe developments such as right bundle branch block or ventricular premature complexes in a greater number of dogs. PMID:23148870

  9. Development of Methods for Coordinate Measurement of Total Cell-Associated and Integrated Human Immunodeficiency Virus Type 1 (HIV-1) DNA Forms in Routine Clinical Samples: Levels Are Not Associated with Clinical Parameters, but Low Levels of Integrated HIV-1 DNA May Be Prognostic for Continued Successful Therapy▿

    PubMed Central

    Carr, J. M.; Cheney, K. M.; Coolen, C.; Davis, A.; Shaw, D.; Ferguson, W.; Chang, G.; Higgins, G.; Burrell, C.; Li, P.

    2007-01-01

    We have adapted our established Alu PCR assay for proviral DNA and PCR for total cellular DNA to a real-time PCR format and applied these to human immunodeficiency virus (HIV)-positive specimens collected for routine determination of the plasma viral load (pVL). In a cohort of five patients, measurements of integrated viral load (iVL) and cell-associated viral load (cVL) in CD4+ cells isolated by a single positive selection step were not indicative of HIV DNA levels in the circulation, and further analysis was performed on peripheral blood mononuclear cells (PBMC). In a cohort of 46 samples total cVL was quantitated in most samples, but iVL could be quantitated in only 47.8%, since in 26% iVL was undetectable and in 21.7% the results were invalid due to high levels of unintegrated HIV DNA. There was no correlation of cVL or iVL with pVL, CD4 count, or duration of successful antiretroviral treatment. Out of 26 patients with undetectable pVL, 4 patients failed therapy within the subsequent 12 months and had higher than average iVL, but this was not the case for cVL. Among nine patients with long-term undetectable pVL, no consistent decline in cVL or iVL was seen with time, and changes in cVL and iVL within a patient could be concordant or discordant. These results show that cVL and iVL can be coordinately measured in PBMC from clinical samples but do not correlate with pVL, CD4 counts, or length of suppressive antiretroviral therapy. Interestingly, a high iVL (but not a high cVL) in patients with undetectable pVL was associated with subsequent treatment failure. PMID:17314225

  10. Clinical Significance of an HPV DNA Chip Test with Emphasis on HPV-16 and/or HPV-18 Detection in Korean Gynecological Patients

    PubMed Central

    Yeo, Min-Kyung; Lee, Ahwon; Hur, Soo Young; Park, Jong Sup

    2016-01-01

    Background: Human papillomavirus (HPV) is a major risk factor for cervical cancer. Methods: We evaluated the clinical significance of the HPV DNA chip genotyping assay (MyHPV chip, Mygene Co.) compared with the Hybrid Capture 2 (HC2) chemiluminescent nucleic acid hybridization kit (Digene Corp.) in 867 patients. Results: The concordance rate between the MyHPV chip and HC2 was 79.4% (kappa coefficient, κ = 0.55). The sensitivity and specificity of both HPV tests were very similar (approximately 85% and 50%, respectively). The addition of HPV result (either MyHPV chip or HC2) to cytology improved the sensitivity (95%, each) but reduced the specificity (approximately 30%, each) compared with the HPV test or cytology alone. Based on the MyHPV chip results, the odds ratio (OR) for ≥ high-grade squamous intraepithelial lesions (HSILs) was 9.9 in the HPV-16/18 (+) group and 3.7 in the non-16/18 high-risk (HR)-HPV (+) group. Based on the HC2 results, the OR for ≥ HSILs was 5.9 in the HR-HPV (+) group. When considering only patients with cytological diagnoses of “negative for intraepithelial lesion or malignancy” and “atypical squamous cell or atypical glandular cell,” based on the MyHPV chip results, the ORs for ≥ HSILs were 6.8 and 11.7, respectively, in the HPV-16/18 (+) group. Conclusions: The sensitivity and specificity of the MyHPV chip test are similar to the HC2. Detecting HPV-16/18 with an HPV DNA chip test, which is commonly used in many Asian countries, is useful in assessing the risk of high-grade cervical lesions. PMID:27345180

  11. Cloning and nucleotide sequence of Pseudomonas aeruginosa DNA gyrase gyrA gene from strain PAO1 and quinolone-resistant clinical isolates.

    PubMed Central

    Kureishi, A; Diver, J M; Beckthold, B; Schollaardt, T; Bryan, L E

    1994-01-01

    The Pseudomonas aeruginosa DNA gyrase gyrA gene was cloned and sequenced from strain PAO1. An open reading frame of 2,769 bp was found; it coded for a protein of 923 amino acids with an estimated molecular mass of 103 kDa. The derived amino acid sequence shared 67% identity with Escherichia coli GyrA and 54% identity with Bacillus subtilis GyrA, although conserved regions were present throughout the sequences, particularly toward the N terminus. Complementation of an E. coli mutant with a temperature-sensitive gyrA gene with the PAO1 gyrA gene showed that the gene is expressed in E. coli and is able to functionally complement the E. coli DNA gyrase B subunit. Expression of PAO1 gyrA in E. coli or P. aeruginosa with mutationally altered gyrA genes caused a reversion to wild-type quinolone susceptibility, indicating that the intrinsic susceptibility of the PAO1 GyrA to quinolones is comparable to that of the E. coli enzyme. PCR was used to amplify 360 bp of P. aeruginosa gyrA encompassing the so-called quinolone resistance-determining region from ciprofloxacin-resistant clinical isolates from patients with cystic fibrosis. Mutations were found in three of nine isolates tested; these mutations caused the following alterations in the sequence of GyrA: Asp at position 87 (Asp-87) to Asn, Asp-87 to Tyr, and Thr-83 to Ile. The resistance mechanisms in the other six isolates are unknown. The results of the study suggested that mechanisms other than a mutational alteration in gyrA are the most common mechanism of ciprofloxacin resistance in P. aeruginosa from the lungs of patients with cystic fibrosis. Images PMID:7811002

  12. Quantitative DNA analysis of fresh solid tumors by flow and image cytometric methods: a comparison using the Roche Pathology Workstation Image Analyzer.

    PubMed

    Ellison, D A; Maygarden, S J; Novotny, D B

    1995-04-01

    The clinical utility of DNA ploidy and cell cycle parameters as prognostic indicators has been demonstrated for selected malignant tumors. Previous quantitative DNA analysis studies have used various tumor sample preparation methods and analyzers. We undertook a pilot study to compare the results of DNA analysis of fresh solid tumors by flow cytometry with the new Roche Pathology Workstation Image Analyzer. Flow cytometric DNA analysis was done on cell suspensions of fine needle aspirates from fresh tumor specimens and analyzed for ploidy and cell cycle statistics with a Becton-Dickinson FACScan Analyzer, using a rectangular model. Small aliquots from these same aspirates were prepared as direct cytologic smears and Feulgen stained for DNA analysis with the Roche Image Analyzer. Additional smears were stained with Diff-Quik for morphologic correlation with DNA histograms. The study group consisted of 40 malignant neoplasms. There was a high correlation between the flow and image DNA indices (R = 0.93, slope = 1.0036, P < 0.001) but a weaker relationship between the flow and image estimated S-phase fractions (R = 0.57, slope = 0.5401, P < 0.01). DNA ploidy categorization for the two methods was concordant in 30 (75%) cases, discordant in seven (17.5%) cases, and equivocal in three (7.5%) cases. In our experience, quantitative DNA analysis of fresh tumor aspirates by flow and image cytometric methods yielded comparable and/or complementary results, with each method having certain advantages and disadvantages. Proposed reasons for false and true discordances and an approach for evaluation are discussed. PMID:7617654

  13. NI-20ADC HISTOGRAM ANALYSIS FOLLOWING RADIOTHERAPY PREDICTS RESPONSE TO ADJUVANT TEMOZOLOMIDE IN NEWLY DIAGNOSED GBM

    PubMed Central

    Ellingson, Benjamin; Chang, Warren; Harris, Robert; Mody, Reema; Lai, Albert; Nghiemphu, Phioanh; Cloughesy, Timothy; Pope, Whitney

    2014-01-01

    INTRODUCTION: The current standard of care for newly diagnosed GBM consists of concurrent radiotherapy and temozolomide (TMZ) plus adjuvant TMZ. We hypothesize there is a subset of patients that will have a significant benefit from this adjuvant therapy. Therefore, the purpose of the current study was to identify a diffusion imaging phenotype for patients with newly diagnosed GBM that will benefit from adjuvant TMZ following concurrent radiotherapy and TMZ. METHODS: A total of 120 patients with: 1) histologically confirmed glioblastoma, 2) treated with concurrent radiotherapy and TMZ followed by adjuvant TMZ; and 3) high quality diffusion MR data were included in the current study. Diffusion and standard structural MRI were performed approximately 10 weeks after the start of radiotherapy and concurrent TMZ. ADC histogram analysis was performed by fitting a double Gaussian mixed model to ADC data extracted from contrast enhancement tumor. ADCL was defined as the mean ADC of the lower Gaussian distribution. We hypothesize that patients with a high ADCL have a lower tumor burden and thus favorable response to adjuvant TMZ in terms of TTP and OS. RESULTS: Results demonstrate that patients with an ADCL lower than 1 um2/ms has a significantly shorter PFS compared with patients having a higher ADCL (Log-rank, P < 0.0001), showing almost twice the median PFS (297 days vs. 156 days). Additionally, patients with a high ADCL had a significantly longer OS (Log-rank, P = 0.0049). Patients with a high ADCL had a median OS of 648 days while patients with a low ADCL had a median OS of only 407 days from the start of adjuvant TMZ. CONCLUSION: Newly diagnosed GBM patients with elevated tumor diffusivity after completion of radiotherapy and concurrent TMZ have a favorable prognosis.

  14. Dose-Volume Histogram Analysis of the Safety of Proton Beam Therapy for Unresectable Hepatocellular Carcinoma

    SciTech Connect

    Kawashima, Mitsuhiko; Kohno, Ryosuke; Nakachi, Kohei; Nishio, Teiji; Mitsunaga, Shuichi; Ikeda, Masafumi; Konishi, Masaru; Takahashi, Shinichiro; Gotohda, Naoto; Arahira, Satoko; Zenda, Sadamoto; Ogino, Takashi; Kinoshita, Taira

    2011-04-01

    Purpose: To evaluate the safety and efficacy of radiotherapy using proton beam (PRT) for unresectable hepatocellular carcinoma. Methods and Materials: Sixty consecutive patients who underwent PRT between May 1999 and July 2007 were analyzed. There were 42 males and 18 females, with a median age of 70 years (48-92 years). All but 1 patient had a single lesion with a median diameter of 45 mm (20-100 mm). Total PRT dose/fractionation was 76-cobalt Gray equivalent (CGE)/20 fractions in 46 patients, 65 CGE/26 fractions in 11 patients, and 60 CGE/10 fractions in 3 patients. The risk of developing proton-induced hepatic insufficiency (PHI) was estimated using dose-volume histograms and an indocyanine-green retention rate at 15 minutes (ICG R15). Results: None of the 20 patients with ICG R15 of less than 20% developed PHI, whereas 6 of 8 patients with ICG R15 values of 50% or higher developed PHI. Among 32 patients whose ICG R15 ranged from 20% to 49.9%, PHI was observed only in patients who had received 30 CGE (V30) to more than 25% of the noncancerous parts of the liver (n = 5) Local progression-free and overall survival rates at 3 years were 90% (95% confidence interval [CI], 80-99%) and 56% (95% CI, 43-69%), respectively. A gastrointestinal toxicity of Grade {>=}2 was observed in 3 patients. Conclusions: ICG R15 and V30 are recommended as useful predictors for the risk of developing PHI, which should be incorporated into multidisciplinary treatment plans for patients with this disease.

  15. Assessment of Autonomic Function by Phase Rectification of RRInterval Histogram Analysis in Chagas Disease

    PubMed Central

    Nasari-Junior, Olivassé; Benchimol-Barbosa, Paulo Roberto; Pedrosa, Roberto Coury; Nadal, Jurandir

    2015-01-01

    Background In chronic Chagas disease (ChD), impairment of cardiac autonomic function bears prognostic implications. Phase‑rectification of RR-interval series isolates the sympathetic, acceleration phase (AC) and parasympathetic, deceleration phase (DC) influences on cardiac autonomic modulation. Objective This study investigated heart rate variability (HRV) as a function of RR-interval to assess autonomic function in healthy and ChD subjects. Methods Control (n = 20) and ChD (n = 20) groups were studied. All underwent 60-min head-up tilt table test under ECG recording. Histogram of RR-interval series was calculated, with 100 ms class, ranging from 600–1100 ms. In each class, mean RR-intervals (MNN) and root-mean-squared difference (RMSNN) of consecutive normal RR-intervals that suited a particular class were calculated. Average of all RMSNN values in each class was analyzed as function of MNN, in the whole series (RMSNNT), and in AC (RMSNNAC) and DC (RMSNNDC) phases. Slopes of linear regression lines were compared between groups using Student t-test. Correlation coefficients were tested before comparisons. RMSNN was log-transformed. (α < 0.05). Results Correlation coefficient was significant in all regressions (p < 0.05). In the control group, RMSNNT, RMSNNAC, and RMSNNDC significantly increased linearly with MNN (p < 0.05). In ChD, only RMSNNAC showed significant increase as a function of MNN, whereas RMSNNT and RMSNNDC did not. Conclusion HRV increases in proportion with the RR-interval in healthy subjects. This behavior is lost in ChD, particularly in the DC phase, indicating cardiac vagal incompetence. PMID:26131700

  16. ADC histograms predict response to anti-angiogenic therapy in patients with recurrent high-grade glioma

    PubMed Central

    2011-01-01

    Introduction The purpose of this study is to evaluate apparent diffusion coefficient (ADC) maps to distinguish anti-vascular and anti-tumor effects in the course of anti-angiogenic treatment of recurrent high-grade gliomas (rHGG) as compared to standard magnetic resonance imaging (MRI). Methods This retrospective study analyzed ADC maps from diffusion-weighted MRI in 14 rHGG patients during bevacizumab/irinotecan (B/I) therapy. Applying image segmentation, volumes of contrast-enhanced lesions in T1 sequences and of hyperintense T2 lesions (hT2) were calculated. hT2 were defined as regions of interest (ROI) and registered to corresponding ADC maps (hT2-ADC). Histograms were calculated from hT2-ADC ROIs. Thereafter, histogram asymmetry termed “skewness” was calculated and compared to progression-free survival (PFS) as defined by the Response Assessment Neuro-Oncology (RANO) Working Group criteria. Results At 8–12 weeks follow-up, seven (50%) patients showed a partial response, three (21.4%) patients were stable, and four (28.6%) patients progressed according to RANO criteria. hT2-ADC histograms demonstrated statistically significant changes in skewness in relation to PFS at 6 months. Patients with increasing skewness (n=11) following B/I therapy had significantly shorter PFS than did patients with decreasing or stable skewness values (n=3, median percentage change in skewness 54% versus −3%, p=0.04). Conclusion In rHGG patients, the change in ADC histogram skewness may be predictive for treatment response early in the course of anti-angiogenic therapy and more sensitive than treatment assessment based solely on RANO criteria. PMID:21125399

  17. Microsatellite polymorphisms in DNA repair genes XRCC1, XRCC3 and XRCC5 in patients with gynecological tumors: association with late clinical radiosensitivity and cancer incidence.

    PubMed

    De Ruyck, K; Wilding, C S; Van Eijkeren, M; Morthier, R; Tawn, E J; Thierens, H

    2005-09-01

    This study investigates the association of microsatellite polymorphisms in XRCC1, XRCC3 and XRCC5 with the development of late radiation-induced radiotherapy reactions and examines the correlation between these microsatellites and cancer incidence. Sixty-two women with cervical or endometrial cancer treated with radiotherapy were included in the study. According to the CTCAEv3.0 scale, 22 patients showed late adverse radiotherapy reactions (grade 2 or more). PCR on lymphocyte DNA followed by automated fragment analysis was performed to examine the number of tandem repeat units at each locus. No significant association was found between the repeat length at any of the microsatellites in XRCC1, XRCC3 or XRCC5 and the incidence of late radiotherapy complications. Since higher odds ratios (ORs) were found for the rare XRCC1 [AC]11 and [AC]21 repeats (OR = 2.65, P = 0.325 and OR = 8.67, P = 0.093, respectively), the possible involvement of these small and large repeats in clinical radiosensitivity cannot be completely ruled out. When specific numbers of repeats were examined, no significant correlation was found between the microsatellite repeat length in XRCC1 and XRCC5 and cancer incidence. A weak correlation between XRCC3 [AC]16 homozygotes and cancer incidence was found (OR = 2.56, P = 0.055). A large-scale multicenter study of cancer patients with a high number of radiosensitive individuals is needed to clarify the value of rare polymorphic microsatellite repeats in XRCC1 and XRCC3 as a biomarker of clinical radiosensitivity or increased cancer risk. PMID:16137195

  18. Comparison of the Accuracy of Two Conventional Phenotypic Methods and Two MALDI-TOF MS Systems with That of DNA Sequencing Analysis for Correctly Identifying Clinically Encountered Yeasts

    PubMed Central

    Chao, Qiao-Ting; Lee, Tai-Fen; Teng, Shih-Hua; Peng, Li-Yun; Chen, Ping-Hung; Teng, Lee-Jene; Hsueh, Po-Ren

    2014-01-01

    We assessed the accuracy of species-level identification of two commercially available matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) systems (Bruker Biotyper and Vitek MS) and two conventional phenotypic methods (Phoenix 100 YBC and Vitek 2 Yeast ID) with that of rDNA gene sequencing analysis among 200 clinical isolates of commonly encountered yeasts. The correct identification rates of the 200 yeast isolates to species or complex (Candida parapsilosis complex, C. guilliermondii complex and C. rugosa complex) levels by the Bruker Biotyper, Vitek MS (using in vitro devices [IVD] database), Phoenix 100 YBC and Vitek 2 Yeast ID (Sabouraud's dextrose agar) systems were 92.5%, 79.5%, 89%, and 74%, respectively. An additional 72 isolates of C. parapsilosis complex and 18 from the above 200 isolates (30 in each of C. parapsilosis, C. metapsilosis, and C. orthopsilosis) were also evaluated separately. Bruker Biotyper system could accurately identify all C. parapsilosis complex to species level. Using Vitek 2 MS (IVD) system, all C. parapsilosis but none of C. metapsilosis, or C. orthopsilosis could be accurately identified. Among the 89 yeasts misidentified by the Vitek 2 MS (IVD) system, 39 (43.8%), including 27 C. orthopsilosis isolates, could be correctly identified Using the Vitek MS Plus SARAMIS database for research use only. This resulted in an increase in the rate of correct identification of all yeast isolates (87.5%) by Vitek 2 MS. The two species in C. guilliermondii complex (C. guilliermondii and C. fermentati) isolates were correctly identified by cluster analysis of spectra generated by the Bruker Biotyper system. Based on the results obtained in the current study, MALDI-TOF MS systems present a promising alternative for the routine identification of yeast species, including clinically commonly and rarely encountered yeast species and several species belonging to C. parapsilosis complex, C. guilliermondii complex

  19. DNA methylation patterns in luminal breast cancers differ from non-luminal subtypes and can identify relapse risk independent of other clinical variables.

    PubMed

    Kamalakaran, Sitharthan; Varadan, Vinay; Giercksky Russnes, Hege E; Levy, Dan; Kendall, Jude; Janevski, Angel; Riggs, Michael; Banerjee, Nilanjana; Synnestvedt, Marit; Schlichting, Ellen; Kåresen, Rolf; Shama Prasada, K; Rotti, Harish; Rao, Ramachandra; Rao, Laxmi; Eric Tang, Man-Hung; Satyamoorthy, K; Lucito, Robert; Wigler, Michael; Dimitrova, Nevenka; Naume, Bjorn; Borresen-Dale, Anne-Lise; Hicks, James B

    2011-02-01

    The diversity of breast cancers reflects variations in underlying biology and affects the clinical implications for patients. Gene expression studies have identified five major subtypes- Luminal A, Luminal B, basal-like, ErbB2+ and Normal-Like. We set out to determine the role of DNA methylation in subtypes by performing genome-wide scans of CpG methylation in breast cancer samples with known expression-based subtypes. Unsupervised hierarchical clustering using a set of most varying loci clustered the tumors into a Luminal A majority (82%) cluster, Basal-like/ErbB2+ majority (86%) cluster and a non-specific cluster with samples that were also inconclusive in their expression-based subtype correlations. Contributing methylation loci were both gene associated loci (30%) and non-gene associated (70%), suggesting subtype dependant genome-wide alterations in the methylation landscape. The methylation patterns of significant differentially methylated genes in luminal A tumors are similar to those identified in CD24 + luminal epithelial cells and the patterns in basal-like tumors similar to CD44 + breast progenitor cells. CpG islands in the HOXA cluster and other homeobox (IRX2, DLX2, NKX2-2) genes were significantly more methylated in Luminal A tumors. A significant number of genes (2853, p < 0.05) exhibited expression-methylation correlation, implying possible functional effects of methylation on gene expression. Furthermore, analysis of these tumors by using follow-up survival data identified differential methylation of islands proximal to genes involved in Cell Cycle and Proliferation (Ki-67, UBE2C, KIF2C, HDAC4), angiogenesis (VEGF, BTG1, KLF5), cell fate commitment (SPRY1, OLIG2, LHX2 and LHX5) as having prognostic value independent of subtypes and other clinical factors. PMID:21169070

  20. The clinical significance of EBV DNA in the plasma and peripheral blood mononuclear cells of patients with or without EBV diseases.

    PubMed

    Kanakry, Jennifer A; Hegde, Aparna M; Durand, Christine M; Massie, Allan B; Greer, Amy E; Ambinder, Richard F; Valsamakis, Alexandra

    2016-04-21

    Epstein-Barr virus (EBV) is a ubiquitous virus that establishes a latent infection within the host and in some cases can lead to the development of EBV-associated lymphomas, lymphoproliferative disorders, hemophagocytic lymphohistiocytosis, solid tumors, and other diseases. We studied the clinical significance of detecting EBV DNA in the plasma and peripheral blood mononuclear cells (PBMCs) of 2146 patients who had blood specimens sent to the Johns Hopkins Hospital clinical laboratory for viral quantitative real-time polymerase chain reaction assay over a 5-year period. Within this largely immunocompromised and hospitalized cohort, 535 patients (25%) had EBV detected in plasma or PBMCs. When EBV was detected in the absence of an EBV(+)disease (n = 402), it was present only in PBMCs in 69% of cases. Immunocompromised patients were less likely to have EBV in plasma than in PBMCs in the absence of EBV(+)disease. In patients with active, systemic EBV(+)diseases (n = 105), EBV was detected in plasma in 99% of cases but detected in PBMCs in only 54%. Across a range of copy number cutoffs, EBV in plasma had higher specificity and sensitivity for EBV(+)disease as compared with EBV in PBMCs. EBV copy number in plasma distinguished untreated, EBV(+)lymphoma from EBV(+)lymphoma in remission and EBV(-)lymphoma, and also distinguished untreated, EBV(+)posttransplantation lymphoproliferative disorder (PTLD) from EBV(+)PTLD in remission and EBV(-)PTLD. EBV copy number quantification is a useful diagnostic marker across the spectrum of EBV(+)diseases, even among immunocompromised patients, with plasma specimens more indicative of EBV(+)disease than PBMCs. PMID:26744460

  1. DNA-Mutation Inventory to Refine and Enhance Cancer Treatment (DIRECT): A Catalog of Clinically Relevant Cancer Mutations to Enable Genome-Directed Anticancer Therapy

    PubMed Central

    Yeh, Paul; Chen, Heidi; Andrews, Jenny; Naser, Riyad; Pao, William; Horn, Leora

    2014-01-01

    Purpose Tumor gene mutation status is becoming increasingly important in the treatment of patients with cancer. A comprehensive catalog of tumor gene–response outcomes from individual patients is needed, especially for actionable mutations and rare variants. We created a proof-of-principle database [DNA-mutation Inventory to Refine and Enhance Cancer Treatment (DIRECT)], starting with lung cancer-associated EGF receptor (EGFR) mutations, to provide a resource for clinicians to prioritize treatment decisions based on a patient’s tumor mutations at the point of care. Methods A systematic search of literature published between June 2005 and May 2011 was conducted through PubMed to identify patient-level, mutation–drug response in patients with non–small cell lung cancer (NSCLC) with EGFR mutant tumors. Minimum inclusion criteria included patient’s EGFR mutation, corresponding treatment, and an associated radiographic outcome. Results A total of 1,021 patients with 1,070 separate EGFR tyrosine kinase inhibitor therapy responses from 116 different publications were included. About 188 unique EGFR mutations occurring in 207 different combinations were identified: 149 different mutation combinations were associated with disease control and 42 were associated with disease progression. Four secondary mutations, in 16 different combinations, were associated with acquired resistance. Conclusions As tumor sequencing becomes more common in oncology, this comprehensive electronic catalog can enable genome-directed anticancer therapy. DIRECT will eventually encompass all tumor mutations associated with clinical outcomes on targeted therapies. Users can make specific queries at http:// www.mycancergenome.org/about/direct to obtain clinically relevant data associated with various mutations. PMID:23344264

  2. Comparison of chromosomal aberrations detected by fluorescence in situ hybridization with clinical parameters, DNA ploidy and Ki 67 expression in renal cell carcinoma.

    PubMed Central

    Wada, Y.; Igawa, M.; Shiina, H.; Shigeno, K.; Yokogi, H.; Urakami, S.; Yoneda, T.; Maruyama, R.

    1998-01-01

    To evaluate the significance of chromosomal aberrations in renal cell carcinoma, fluorescence in situ hybridization (FISH) was used to determine its prevalence and correlation with clinical parameters of malignancy. In addition, correlation of chromosomal aberration with Ki 67 expression was analysed. We performed FISH with chromosome-specific DNA probes, and the signal number of pericentromeric sequences on chromosomes 3, 7, 9 and 17 was detected within interphase nuclei in touch preparations from tumour specimen. The incidence of loss of chromosome 3 was significantly higher than those of chromosomes 7, 9 and 17 (P < 0.001, P = 0.03 and P < 0.001 respectively). Hyperdiploid aberration of chromosomes 3 and 17 was significantly correlated with tumour stage (P = 0.03, P = 0.02 respectively), whereas hyperdiploid aberration of chromosome 9 was associated with nuclear grade (P = 0.04). Disomy of chromosome 7 was correlated with venous involvement (P = 0.04). Ki 67 expression was significantly associated with hyperdiploid aberration of chromosome 17 (P = 0.01), but not with aberration of chromosome 3. There was a significant relationship between hyperdiploid aberration of chromosome 7 and Ki 67 expression (P = 0.01). In conclusions, gain of chromosome 17 may reflect tumour development, and aberration of chromosome 7 may affect metastatic potential of malignancy, whereas loss of chromosome 3 may be associated with early stage of tumour development in renal cell carcinoma. PMID:9667682

  3. Sequence Analysis of Herpes Simplex Virus 1 Thymidine Kinase and DNA Polymerase Genes from over 300 Clinical Isolates from 1973 to 2014 Finds Novel Mutations That May Be Relevant for Development of Antiviral Resistance.

    PubMed

    Schmidt, Susanne; Bohn-Wippert, Kathrin; Schlattmann, Peter; Zell, Roland; Sauerbrei, Andreas

    2015-08-01

    A total of 302 clinical herpes simplex virus 1 (HSV-1) strains, collected over 4 decades from 1973 to 2014, were characterized retrospectively for drug resistance. All HSV-1 isolates were analyzed genotypically for nonsynonymous mutations in the thymidine kinase (TK) and DNA polymerase (Pol) genes. The resistance phenotype against acyclovir (ACV) and/or foscarnet (FOS) was examined in the case of novel, unclear, or resistance-related mutations. Twenty-six novel natural polymorphisms could be detected in the TK gene and 69 in the DNA Pol gene. Furthermore, three novel resistance-associated mutations (two in the TK gene and one in the DNA Pol gene) were analyzed, and eight known but hitherto unclear amino acid substitutions (two encoded in TK and six in the DNA Pol gene) could be clarified. Between 1973 and 2014, the distribution of amino acid changes related to the natural gene polymorphisms of TK and DNA Pol remained largely stable. Resistance to ACV was confirmed phenotypically for 16 isolates, and resistance to ACV plus FOS was confirmed for 1 isolate. Acyclovir-resistant strains were observed from the year 1995 onwards, predominantly in immunosuppressed patients, especially those with stem cell transplantation, and the number of ACV-resistant strains increased during the last 2 decades. The data confirm the strong genetic variability among HIV-1 isolates, which is more pronounced in the DNA Pol gene than in the TK gene, and will facilitate considerably the rapid genotypic diagnosis of HSV-1 resistance. PMID:26055375

  4. Human DNA repair genes.

    PubMed

    Wood, R D; Mitchell, M; Sgouros, J; Lindahl, T

    2001-02-16

    Cellular DNA is subjected to continual attack, both by reactive species inside cells and by environmental agents. Toxic and mutagenic consequences are minimized by distinct pathways of repair, and 130 known human DNA repair genes are described here. Notable features presently include four enzymes that can remove uracil from DNA, seven recombination genes related to RAD51, and many recently discovered DNA polymerases that bypass damage, but only one system to remove the main DNA lesions induced by ultraviolet light. More human DNA repair genes will be found by comparison with model organisms and as common folds in three-dimensional protein structures are determined. Modulation of DNA repair should lead to clinical applications including improvement of radiotherapy and treatment with anticancer drugs and an advanced understanding of the cellular aging process. PMID:11181991

  5. Visual vs Fully Automatic Histogram-Based Assessment of Idiopathic Pulmonary Fibrosis (IPF) Progression Using Sequential Multidetector Computed Tomography (MDCT)

    PubMed Central

    Colombi, Davide; Dinkel, Julien; Weinheimer, Oliver; Obermayer, Berenike; Buzan, Teodora; Nabers, Diana; Bauer, Claudia; Oltmanns, Ute; Palmowski, Karin; Herth, Felix; Kauczor, Hans Ulrich; Sverzellati, Nicola

    2015-01-01

    Objectives To describe changes over time in extent of idiopathic pulmonary fibrosis (IPF) at multidetector computed tomography (MDCT) assessed by semi-quantitative visual scores (VSs) and fully automatic histogram-based quantitative evaluation and to test the relationship between these two methods of quantification. Methods Forty IPF patients (median age: 70 y, interquartile: 62-75 years; M:F, 33:7) that underwent 2 MDCT at different time points with a median interval of 13 months (interquartile: 10-17 months) were retrospectively evaluated. In-house software YACTA quantified automatically lung density histogram (10th-90th percentile in 5th percentile steps). Longitudinal changes in VSs and in the percentiles of attenuation histogram were obtained in 20 untreated patients and 20 patients treated with pirfenidone. Pearson correlation analysis was used to test the relationship between VSs and selected percentiles. Results In follow-up MDCT, visual overall extent of parenchymal abnormalities (OE) increased in median by 5 %/year (interquartile: 0 %/y; +11 %/y). Substantial difference was found between treated and untreated patients in HU changes of the 40th and of the 80th percentiles of density histogram. Correlation analysis between VSs and selected percentiles showed higher correlation between the changes (Δ) in OE and Δ 40th percentile (r=0.69; p<0.001) as compared to Δ 80th percentile (r=0.58; p<0.001); closer correlation was found between Δ ground-glass extent and Δ 40th percentile (r=0.66, p<0.001) as compared to Δ 80th percentile (r=0.47, p=0.002), while the Δ reticulations correlated better with the Δ 80th percentile (r=0.56, p<0.001) in comparison to Δ 40th percentile (r=0.43, p=0.003). Conclusions There is a relevant and fully automatically measurable difference at MDCT in VSs and in histogram analysis at one year follow-up of IPF patients, whether treated or untreated: Δ 40th percentile might reflect the change in overall extent of lung

  6. Nanothermodynamics of large iron clusters by means of a flat histogram Monte Carlo method

    SciTech Connect

    Basire, M.; Soudan, J.-M.; Angelié, C.

    2014-09-14

    The thermodynamics of iron clusters of various sizes, from 76 to 2452 atoms, typical of the catalyst particles used for carbon nanotubes growth, has been explored by a flat histogram Monte Carlo (MC) algorithm (called the σ-mapping), developed by Soudan et al. [J. Chem. Phys. 135, 144109 (2011), Paper I]. This method provides the classical density of states, g{sub p}(E{sub p}) in the configurational space, in terms of the potential energy of the system, with good and well controlled convergence properties, particularly in the melting phase transition zone which is of interest in this work. To describe the system, an iron potential has been implemented, called “corrected EAM” (cEAM), which approximates the MEAM potential of Lee et al. [Phys. Rev. B 64, 184102 (2001)] with an accuracy better than 3 meV/at, and a five times larger computational speed. The main simplification concerns the angular dependence of the potential, with a small impact on accuracy, while the screening coefficients S{sub ij} are exactly computed with a fast algorithm. With this potential, ergodic explorations of the clusters can be performed efficiently in a reasonable computing time, at least in the upper half of the solid zone and above. Problems of ergodicity exist in the lower half of the solid zone but routes to overcome them are discussed. The solid-liquid (melting) phase transition temperature T{sub m} is plotted in terms of the cluster atom number N{sub at}. The standard N{sub at}{sup −1/3} linear dependence (Pawlow law) is observed for N{sub at} >300, allowing an extrapolation up to the bulk metal at 1940 ±50 K. For N{sub at} <150, a strong divergence is observed compared to the Pawlow law. The melting transition, which begins at the surface, is stated by a Lindemann-Berry index and an atomic density analysis. Several new features are obtained for the thermodynamics of cEAM clusters, compared to the Rydberg pair potential clusters studied in Paper I.

  7. Dose-Volume Histogram Predictors of Chronic Gastrointestinal Complications After Radical Hysterectomy and Postoperative Concurrent Nedaplatin-Based Chemoradiation Therapy for Early-Stage Cervical Cancer

    SciTech Connect

    Isohashi, Fumiaki; Yoshioka, Yasuo; Mabuchi, Seiji; Konishi, Koji; Koizumi, Masahiko; Takahashi, Yutaka; Ogata, Toshiyuki; Maruoka, Shintaroh; Kimura, Tadashi; Ogawa, Kazuhiko

    2013-03-01

    Purpose: The purpose of this study was to evaluate dose-volume histogram (DVH) predictors for the development of chronic gastrointestinal (GI) complications in cervical cancer patients who underwent radical hysterectomy and postoperative concurrent nedaplatin-based chemoradiation therapy. Methods and Materials: This study analyzed 97 patients who underwent postoperative concurrent chemoradiation therapy. The organs at risk that were contoured were the small bowel loops, large bowel loop, and peritoneal cavity. DVH parameters subjected to analysis included the volumes of these organs receiving more than 15, 30, 40, and 45 Gy (V15-V45) and their mean dose. Associations between DVH parameters or clinical factors and the incidence of grade 2 or higher chronic GI complications were evaluated. Results: Of the clinical factors, smoking and low body mass index (BMI) (<22) were significantly associated with grade 2 or higher chronic GI complications. Also, patients with chronic GI complications had significantly greater V15-V45 volumes and higher mean dose of the small bowel loops compared with those without GI complications. In contrast, no parameters for the large bowel loop or peritoneal cavity were significantly associated with GI complications. Results of the receiver operating characteristics (ROC) curve analysis led to the conclusion that V15-V45 of the small bowel loops has high accuracy for prediction of GI complications. Among these parameters, V40 gave the highest area under the ROC curve. Finally, multivariate analysis was performed with V40 of the small bowel loops and 2 other clinical parameters that were judged to be potential risk factors for chronic GI complications: BMI and smoking. Of these 3 parameters, V40 of the small bowel loops and smoking emerged as independent predictors of chronic GI complications. Conclusions: DVH parameters of the small bowel loops may serve as predictors of grade 2 or higher chronic GI complications after postoperative

  8. Carcinoma of the anal canal and flow cytometric DNA analysis.

    PubMed Central

    Scott, N. A.; Beart, R. W.; Weiland, L. H.; Cha, S. S.; Lieber, M. M.

    1989-01-01

    Using flow cytometric DNA analysis of paraffin embedded tissue, DNA histograms were successfully obtained from the anal cancers of 117 patients. DNA diploid patterns were given by 82 cancers (70%) and DNA non-diploid patterns by 35 cancers (30%): 15 DNA aneuploid, 20 DNA tetraploid. Well differentiated squamous cell cancers were mainly DNA diploid, while a larger proportion of poorly differentiated and small cell cancers were DNA non-diploid. The large majority of stage A cancers were DNA diploid. A greater proportion of tumours that had invaded through the anal sphincter or had lymph node metastases or distant spread were DNA non-diploid. Prognosis was slightly poorer for patients with DNA non-diploid cancers when compared to patients with DNA diploid tumours (P = 0.08) and significantly poorer for individuals with DNA aneuploid anal cancers (P = 0.037). However, in a multivariate analysis model, the DNA ploidy pattern of an anal cancer was not of independent prognostic significance alongside tumour histology and tumour stage. PMID:2803916

  9. Development and Validation of a Laboratory-Developed Multiplex Real-Time PCR Assay on the BD Max System for Detection of Herpes Simplex Virus and Varicella-Zoster Virus DNA in Various Clinical Specimens

    PubMed Central

    Pillet, Sylvie; Verhoeven, Paul O.; Epercieux, Amélie; Bourlet, Thomas

    2015-01-01

    A multiplex real-time PCR (quantitative PCR [qPCR]) assay detecting herpes simplex virus (HSV) and varicella-zoster virus (VZV) DNA together with an internal control was developed on the BD Max platform combining automated DNA extraction and an open amplification procedure. Its performance was compared to those of PCR assays routinely used in the laboratory, namely, a laboratory-developed test for HSV DNA on the LightCycler instrument and a test using a commercial master mix for VZV DNA on the ABI7500fast system. Using a pool of negative cerebrospinal fluid (CSF) samples spiked with either calibrated controls for HSV-1 and VZV or dilutions of a clinical strain that was previously quantified for HSV-2, the empirical limit of detection of the BD Max assay was 195.65, 91.80, and 414.07 copies/ml for HSV-1, HSV-2, and VZV, respectively. All the samples from HSV and VZV DNA quality control panels (Quality Control for Molecular Diagnostics [QCMD], 2013, Glasgow, United Kingdom) were correctly identified by the BD Max assay. From 180 clinical specimens of various origins, 2 CSF samples were found invalid by the BD Max assay due to the absence of detection of the internal control; a concordance of 100% was observed between the BD Max assay and the corresponding routine tests. The BD Max assay detected the PCR signal 3 to 4 cycles earlier than did the routine methods. With results available within 2 h on a wide range of specimens, this sensitive and fully automated PCR assay exhibited the qualities required for detecting simultaneously HSV and VZV DNA on a routine basis. PMID:25878344

  10. Genetic Diversity of Mycobacterium africanum Clinical Isolates Based on IS6110-Restriction Fragment Length Polymorphism Analysis, Spoligotyping, and Variable Number of Tandem DNA Repeats

    PubMed Central

    Viana-Niero, Cristina; Gutierrez, Cristina; Sola, Christophe; Filliol, Ingrid; Boulahbal, Fadila; Vincent, Véronique; Rastogi, Nalin

    2001-01-01

    A collection of 105 clinical isolates originally identified as Mycobacterium africanum were characterized using both phenotypic and genotyping methods. The phenotypic methods included routine determination of cultural properties and biochemical tests used to discriminate among the members of the M. tuberculosis complex, whereas genotypic characterization was based on IS6110-restriction fragment length polymorphism (IS6110-RFLP) analysis, IS1081-RFLP analysis, direct repeat-based spacer oligonucleotide typing (spoligotyping), variable number of tandem DNA repeats (VNTR), and the polymorphism of the oxyR, pncA, and mtp40 loci. The results obtained showed that a majority of M. africanum isolates were characterized by a specific spoligotyping pattern that was intermediate between those of M. tuberculosis and M. bovis, which do not hybridize with spacers 33 to 36 and spacers 39 to 43, respectively. A tentative M. africanum-specific spoligotyping signature appeared to be absence of spacers 8, 9, and 39. Based on spoligotyping, as well as the polymorphism of oxyR and pncA, a total of 24 isolates were excluded from the final study (19 were identified as M. tuberculosis, 2 were identified as M. canetti, and 3 were identified as M. bovis). The remaining 81 M. africanum isolates were efficiently subtyped in three distinct subtypes (A1 to A3) by IS6110-RFLP analysis and spoligotyping. The A1 and A2 subgroups were relatively more homogeneous upon spoligotyping than A3. Further analysis of the three subtypes by VNTR corroborated the highly homogeneous nature of the A2 subtype but showed significant variations for subtypes A1 and A3. A phylogenetic tree based on a selection of isolates representing the three subtypes using VNTR and spoligotyping alone or in combination confirmed the subtypes described as well as the heterogeneity of subtype A3. PMID:11136749

  11. The detection of Felis catus papillomavirus 3 DNA in a feline bowenoid in situ carcinoma with novel histologic features and benign clinical behavior.

    PubMed

    Munday, John S; Fairley, Rob; Atkinson, Karen

    2016-09-01

    Bowenoid in situ carcinoma (BISC; papillomavirus-associated squamous cell carcinoma in situ) is an uncommon skin neoplasm of cats that can result in euthanasia because of the development of multiple lesions or because of progression to invasive squamous cell carcinoma. BISCs are currently thought to be caused by Felis catus papillomavirus 2 (FcaPV-2). The presently described cat developed a single 0.5 cm in diameter interscapular mass. Over the following 18 months, the mass doubled in size; no additional lesions developed. The mass was surgically excised and histologically diagnosed as a BISC. However, in contrast to previously reported BISCs, neither prominent thickening of the deep aspects of the follicular infundibula nor marked cell dysplasia were present. Furthermore, ~50% of the keratinocytes in the affected epidermis had prominent PV cytopathic changes that included shrunken angular nuclei and elongated basophilic cytoplasmic inclusions. As the histopathology was not typical for FcaPV-2 infection, polymerase chain reaction was performed and revealed only DNA sequences from Felis catus papillomavirus 3 (FcaPV-3). No further BISCs developed in this cat 6 months postremoval, hence surgical excision appeared to be curative. Results from this case suggest that, although FcaPV-2 appears to be the predominant cause of BISCs in cats, infection by FcaPV-3 can also cause these neoplasms. BISCs caused by FcaPV-3 appear to have unique histologic features that allow the causative PV type to be predicted. Results from this single case suggest that BISCs caused by FcaPV-3 may have a more benign clinical course than those caused by FcaPV-2. PMID:27423734

  12. Evaluation of culture methods and a DNA probe-based PCR assay for detection of Campylobacter species in clinical specimens of feces.

    PubMed

    Maher, Majella; Finnegan, Cathriona; Collins, Evelyn; Ward, Brid; Carroll, Cyril; Cormican, Martin

    2003-07-01

    Campylobacter species are the leading agents of bacterial gastroenteritis in developed countries. In this study 320 specimens of feces from patients with symptoms of acute gastroenteritis were cultured for Campylobacter species by direct plating on modified charcoal cefoperazone deoxycholate agar and by enrichment in modified Preston broth, with or without blood added, for 48 h at 37 degrees C prior to plating. A 16S/23S PCR/DNA probe membrane-based colorimetric detection assay was evaluated on a subset of the feces (n = 127), including 18 culture-positive and 109 culture-negative specimens. DNA was extracted directly from the fecal specimens by using the QIAamp DNA stool Minikit for the DNA probe-based PCR assay (PCR/DNA probe assay). A second PCR/DNA probe assay based on the 16S rRNA gene in Campylobacter spp. was applied to all specimens that were culture negative, PCR/DNA positive on initial analysis. Campylobacter species were cultured in 20 of the 320 specimens. The 16S/23S PCR/DNA probe assay detected campylobacter DNA in 17 of 18 (94% sensitivity) culture-positive specimens and in 41 (38%) culture-negative specimens. The presence of campylobacter DNA in 35 of 41 culture-negative specimens was confirmed by the 16S PCR/DNA probe assay. DNA sequence analysis of seven 16S/23S PCR products and five 16S PCR products amplified from a selection of these specimens confirmed the presence of campylobacter DNA and more specifically Campylobacter jejuni, C. concisus, C. curvus, and C. gracilis DNA in these specimens. The molecular assays described in this study are rapid methods for the detection and identification of Campylobacter species in fecal specimens. The finding of Campylobacter spp. DNA in a large number of specimens of feces from patients with no other identified cause of diarrhea may suggest that Campylobacter spp. other than C. jejuni and C. coli may account for a proportion of cases of acute gastroenteritis in which no etiological agent is currently

  13. Evaluation of Culture Methods and a DNA Probe-Based PCR Assay for Detection of Campylobacter Species in Clinical Specimens of Feces

    PubMed Central

    Maher, Majella; Finnegan, Cathriona; Collins, Evelyn; Ward, Brid; Carroll, Cyril; Cormican, Martin

    2003-01-01

    Campylobacter species are the leading agents of bacterial gastroenteritis in developed countries. In this study 320 specimens of feces from patients with symptoms of acute gastroenteritis were cultured for Campylobacter species by direct plating on modified charcoal cefoperazone deoxycholate agar and by enrichment in modified Preston broth, with or without blood added, for 48 h at 37°C prior to plating. A 16S/23S PCR/DNA probe membrane-based colorimetric detection assay was evaluated on a subset of the feces (n = 127), including 18 culture-positive and 109 culture-negative specimens. DNA was extracted directly from the fecal specimens by using the QIAamp DNA stool Minikit for the DNA probe-based PCR assay (PCR/DNA probe assay). A second PCR/DNA probe assay based on the 16S rRNA gene in Campylobacter spp. was applied to all specimens that were culture negative, PCR/DNA positive on initial analysis. Campylobacter species were cultured in 20 of the 320 specimens. The 16S/23S PCR/DNA probe assay detected campylobacter DNA in 17 of 18 (94% sensitivity) culture-positive specimens and in 41 (38%) culture-negative specimens. The presence of campylobacter DNA in 35 of 41 culture-negative specimens was confirmed by the 16S PCR/DNA probe assay. DNA sequence analysis of seven 16S/23S PCR products and five 16S PCR products amplified from a selection of these specimens confirmed the presence of campylobacter DNA and more specifically Campylobacter jejuni, C. concisus, C. curvus, and C. gracilis DNA in these specimens. The molecular assays described in this study are rapid methods for the detection and identification of Campylobacter species in fecal specimens. The finding of Campylobacter spp. DNA in a large number of specimens of feces from patients with no other identified cause of diarrhea may suggest that Campylobacter spp. other than C. jejuni and C. coli may account for a proportion of cases of acute gastroenteritis in which no etiological agent is currently identified

  14. Relationship between DNA ploidy level and tumor sociology behavior in 12 nervous cell lines

    SciTech Connect

    Kiss, R.; Camby, I.; Salmon, I.

    1995-06-01

    Cell population sociology was studied in two medulloblastomas and 10 astrocytic human tumor cell lines by means of the characterization of the structure of neoplastic cell colonies growing on histological slides. This was carried out via digital cell image analysis of Feulgen-stained nuclei, to which the Delaunay triangulation and Voronoi paving mathematical techniques were applied. Such assessments were compared to the DNA ploidy level (assessed by means of DNA histogram typing). The results show that the cell colony architecture characteristics differed markedly according to whether the cell lines were euploid (diploid or tetraploid) or aneuploid (hyperdiploid, triploid, hypertriploid, or polymorphic). In fact, the cell colonies from the euploid cell nuclei populations were larger and more dense than those from the aneuploid ones. Furthermore, for an identical period of culture, the cell lines from high-grade malignant astrocytic tumors (glioblastomas) exhibited cell colonies that were larger and more dense than those in cell lines from low-grade astrocytic tumors (astrocytomas). In each of these two groups, the diploid cell nuclei populations exhibited cell colonies larger and more dense than the nondiploid colonies. The present methodology is now being applied in vivo to histological sections of surgically removed human brain tumors in order to distinguish between high-risk clinical subgroups and medium-risk subgroups in clearly circumscribed histopathological groups. 38 refs., 5 figs., 2 tabs.

  15. Angiogenic response of locally advanced breast cancer to neoadjuvant chemotherapy evaluated with parametric histogram from dynamic contrast-enhanced MRI

    NASA Astrophysics Data System (ADS)

    Chang, Yeun-Chung; Huang, Chiun-Sheng; Liu, Yi-Jui; Chen, Jyh-Horng; Lu, Yen-Shen; Tseng, Wen-Yih I.

    2004-08-01

    The aim of this study was to evaluate angiogenic compositions and tumour response in the course of neoadjuvant chemotherapy in patients with locally advanced breast cancer (LABC) using dynamic contrast-enhanced (DCE) MRI. Thirteen patients with LABC underwent serial DCE MRI during the course of chemotherapy. DCE MRI was quantified using a two-compartment model on a pixel-by-pixel basis. Analysis of parametric histograms of amplitude, exchange rate kout and peak enhancement over the whole tumour was performed. The distribution patterns of histograms were correlated with the tumour response. Initial kurtosis and standard deviation of amplitude before chemotherapy correlated with tumour response, r = 0.63 and r = 0.61, respectively. Comparing the initial values with the values after the first course of chemotherapy, tumour response was associated with a decrease in standard deviation of amplitude (r = 0.79), and an increase in kurtosis and a decrease in standard deviation of kout (r = 0.57 and 0.57, respectively). Comparing the initial values with the values after completing the chemotherapy, tumours with better response were associated with an increase in kurtosis (r = 0.62), a decrease in mean (r = 0.84) and standard deviation (r = 0.77) of amplitude, and a decrease in mean of peak enhancement (r = 0.71). Our results suggested that tumours with better response tended to alter their internal compositions from heterogeneous to homogeneous distributions and a decrease in peak enhancement after chemotherapy. Serial analyses of parametric histograms of DCE MRI-derived angiogenic parameters are potentially useful to monitor the response of angiogenic compositions of a tumour throughout the course of chemotherapy, and might predict tumour response early in the course.

  16. Cytokine and iNOS profiles in lymph nodes of dogs naturally infected with Leishmania infantum and their association with the parasitic DNA load and clinical and histopathological features.

    PubMed

    de Vasconcelos, Tassia Cristina Bello; Doyen, Noelle; Cavaillon, Jean-Marc; Bruno, Sávio Freire; de Campos, Monique Paiva; de Miranda, Luisa Helena Monteiro; Madeira, Maria de Fátima; Belo, Vinícius Silva; Figueiredo, Fabiano Borges

    2016-08-30

    In South America, visceral leishmaniasis is a zoonotic disease with severe evolution characteristics in humans, and dogs are its main reservoir. In this context, this study aimed to evaluate the clinical status of dogs from a Brazilian endemic area naturally, at Barra Mansa municipality, infected with Leishmania infantum, in conjunction with their histopathological profile and, in order to determine possible markers of susceptibility or resistance to the disease, parasitic DNA load, cytokine and iNOS mRNA expression profiles were investigated in lymph nodes. High levels of IFN-ɣ and IL-6 mRNA were detected. Both IFN-ɣ and IL-6 mRNA were associated with disorganization of the corticomedullary region. IFN-ɣ and TNF-α mRNA were associated with the absence of follicular hyperplasia. The regulatory pathway was remarkable with IL-10 mRNA detection and its significant association with the severity of the disease. Plasmacytosis and sinus histiocytosis were associated with high loads of parasitic DNA, but there was no significant association between the parasite DNA load and animal clinical alterations. Since high parasitic loads were found in animals with or without symptoms, clinical examination cannot be considered as a criterion for disease susceptibility assessment. PMID:27523930

  17. Linear and Nonlinear Statistical Characterization of DNA

    NASA Astrophysics Data System (ADS)

    Norio Oiwa, Nestor; Goldman, Carla; Glazier, James

    2002-03-01

    We find spatial order in the distribution of protein-coding (including RNAs) and control segments of GenBank genomic sequences, irrespective of ATCG content. This is achieved by correlations, histograms, fractal dimensions and singularity spectra. Estimates of these quantities in complete nuclear genome indicate that coding sequences are long-range correlated and their disposition are self-similar (multifractal) for eukaryotes. These characteristics are absent in prokaryotes, where there are few noncoding sequences, suggesting the `junk' DNA play a relevant role to the genome structure and function. Concerning the genetic message of ATCG sequences, we build a random walk (Levy flight), using DNA symmetry arguments, where we associate A, T, C and G as left, right, down and up steps, respectively. Nonlinear analysis of mitochondrial DNA walks reveal multifractal pattern based on palindromic sequences, which fold in hairpins and loops.

  18. Cleaving DNA with DNA

    NASA Astrophysics Data System (ADS)

    Carmi, Nir; Balkhi, Shameelah R.; Breaker, Ronald R.

    1998-03-01

    A DNA structure is described that can cleave single-stranded DNA oligonucleotides in the presence of ionic copper. This ``deoxyribozyme'' can self-cleave or can operate as a bimolecular complex that simultaneously makes use of duplex and triplex interactions to bind and cleave separate DNA substrates. Bimolecular deoxyribozyme-mediated strand scission proceeds with a kobs of 0.2 min-1, whereas the corresponding uncatalyzed reaction could not be detected. The duplex and triplex recognition domains can be altered, making possible the targeted cleavage of single-stranded DNAs with different nucleotide sequences. Several small synthetic DNAs were made to function as simple ``restriction enzymes'' for the site-specific cleavage of single-stranded DNA.

  19. Modeling the dark current histogram induced by gold contamination in complementary-metal-oxide-semiconductor image sensors

    NASA Astrophysics Data System (ADS)

    Domengie, F.; Morin, P.; Bauza, D.

    2015-07-01

    We propose a model for dark current induced by metallic contamination in a CMOS image sensor. Based on Shockley-Read-Hall kinetics, the expression of dark current proposed accounts for the electric field enhanced emission factor due to the Poole-Frenkel barrier lowering and phonon-assisted tunneling mechanisms. To that aim, we considered the distribution of the electric field magnitude and metal atoms in the depth of the pixel. Poisson statistics were used to estimate the random distribution of metal atoms in each pixel for a given contamination dose. Then, we performed a Monte-Carlo-based simulation for each pixel to set the number of metal atoms the pixel contained and the enhancement factor each atom underwent, and obtained a histogram of the number of pixels versus dark current for the full sensor. Excellent agreement with the dark current histogram measured on an ion-implanted gold-contaminated imager has been achieved, in particular, for the description of the distribution tails due to the pixel regions in which the contaminant atoms undergo a large electric field. The agreement remains very good when increasing the temperature by 15 °C. We demonstrated that the amplification of the dark current generated for the typical electric fields encountered in the CMOS image sensors, which depends on the nature of the metal contaminant, may become very large at high electric field. The electron and hole emissions and the resulting enhancement factor are described as a function of the trap characteristics, electric field, and temperature.

  20. Elucidating the effects of adsorbent flexibility on fluid adsorption using simple models and flat-histogram sampling methods

    SciTech Connect

    Shen, Vincent K. Siderius, Daniel W.

    2014-06-28

    Using flat-histogram Monte Carlo methods, we investigate the adsorptive behavior of the square-well fluid in two simple slit-pore-like models intended to capture fundamental characteristics of flexible adsorbent materials. Both models require as input thermodynamic information about the flexible adsorbent material itself. An important component of this work involves formulating the flexible pore models in the appropriate thermodynamic (statistical mechanical) ensembles, namely, the osmotic ensemble and a variant of the grand-canonical ensemble. Two-dimensional probability distributions, which are calculated using flat-histogram methods, provide the information necessary to determine adsorption thermodynamics. For example, we are able to determine precisely adsorption isotherms, (equilibrium) phase transition conditions, limits of stability, and free energies for a number of different flexible adsorbent materials, distinguishable as different inputs into the models. While the models used in this work are relatively simple from a geometric perspective, they yield non-trivial adsorptive behavior, including adsorption-desorption hysteresis solely due to material flexibility and so-called “breathing” of the adsorbent. The observed effects can in turn be tied to the inherent properties of the bare adsorbent. Some of the effects are expected on physical grounds while others arise from a subtle balance of thermodynamic and mechanical driving forces. In addition, the computational strategy presented here can be easily applied to more complex models for flexible adsorbents.

  1. Priming with a Simplified Intradermal HIV-1 DNA Vaccine Regimen followed by Boosting with Recombinant HIV-1 MVA Vaccine Is Safe and Immunogenic: A Phase IIa Randomized Clinical Trial

    PubMed Central

    Nilsson, Charlotta; Joachim, Agricola; Geldmacher, Christof; Mann, Philipp; Moshiro, Candida; Aboud, Said; Lyamuya, Eligius; Maboko, Leonard; Missanga, Marco; Kaluwa, Bahati; Mfinanga, Sayoki; Podola, Lilly; Bauer, Asli; Godoy-Ramirez, Karina; Marovich, Mary; Moss, Bernard; Hoelscher, Michael; Gotch, Frances; Stöhr, Wolfgang; Stout, Richard; McCormack, Sheena; Wahren, Britta; Mhalu, Fred; Robb, Merlin L.; Biberfeld, Gunnel; Sandström, Eric; Bakari, Muhammad

    2015-01-01

    Background Intradermal priming with HIV-1 DNA plasmids followed by HIV-1MVA boosting induces strong and broad cellular and humoral immune responses. In our previous HIVIS-03 trial, we used 5 injections with 2 pools of HIV-DNA at separate sites for each priming immunization. The present study explores whether HIV-DNA priming can be simplified by reducing the number of DNA injections and administration of combined versus separated plasmid pools. Methods In this phase IIa, randomized trial, priming was performed using 5 injections of HIV-DNA, 1000 μg total dose, (3 Env and 2 Gag encoding plasmids) compared to two “simplified” regimens of 2 injections of HIV-DNA, 600 μg total dose, of Env- and Gag-encoding plasmid pools with each pool either administered separately or combined. HIV-DNA immunizations were given intradermally at weeks 0, 4, and 12. Boosting was performed intramuscularly with 108 pfu HIV-MVA at weeks 30 and 46. Results 129 healthy Tanzanian participants were enrolled. There were no differences in adverse events between the groups. The proportion of IFN-γ ELISpot responders to Gag and/or Env peptides after the second HIV-MVA boost did not differ significantly between the groups primed with 2 injections of combined HIV-DNA pools, 2 injections with separated pools, and 5 injections with separated pools (90%, 97% and 97%). There were no significant differences in the magnitude of Gag and/or Env IFN-γ ELISpot responses, in CD4+ and CD8+ T cell responses measured as IFN-γ/IL-2 production by intracellular cytokine staining (ICS) or in response rates and median titers for binding antibodies to Env gp160 between study groups. Conclusions A simplified intradermal vaccination regimen with 2 injections of a total of 600 μg with combined HIV-DNA plasmids primed cellular responses as efficiently as the standard regimen of 5 injections of a total of 1000 μg with separated plasmid pools after boosting twice with HIV-MVA. Trial Registration World Health

  2. DNA repair

    SciTech Connect

    Friedberg, E.C.; Hanawalt, P.C. )

    1988-01-01

    Topics covered in this book included: Eukaryote model systems for DNA repair study; Sensitive detection of DNA lesions and their repair; and Defined DNA sequence probes for analysis of mutagenesis and repair.

  3. DNA Microarrays

    NASA Astrophysics Data System (ADS)

    Nguyen, C.; Gidrol, X.

    Genomics has revolutionised biological and biomedical research. This revolution was predictable on the basis of its two driving forces: the ever increasing availability of genome sequences and the development of new technology able to exploit them. Up until now, technical limitations meant that molecular biology could only analyse one or two parameters per experiment, providing relatively little information compared with the great complexity of the systems under investigation. This gene by gene approach is inadequate to understand biological systems containing several thousand genes. It is essential to have an overall view of the DNA, RNA, and relevant proteins. A simple inventory of the genome is not sufficient to understand the functions of the genes, or indeed the way that cells and organisms work. For this purpose, functional studies based on whole genomes are needed. Among these new large-scale methods of molecular analysis, DNA microarrays provide a way of studying the genome and the transcriptome. The idea of integrating a large amount of data derived from a support with very small area has led biologists to call these chips, borrowing the term from the microelectronics industry. At the beginning of the 1990s, the development of DNA chips on nylon membranes [1, 2], then on glass [3] and silicon [4] supports, made it possible for the first time to carry out simultaneous measurements of the equilibrium concentration of all the messenger RNA (mRNA) or transcribed RNA in a cell. These microarrays offer a wide range of applications, in both fundamental and clinical research, providing a method for genome-wide characterisation of changes occurring within a cell or tissue, as for example in polymorphism studies, detection of mutations, and quantitative assays of gene copies. With regard to the transcriptome, it provides a way of characterising differentially expressed genes, profiling given biological states, and identifying regulatory channels.

  4. Immunization with DNA vaccines containing porcine reproductive and respiratory syndrome virus open reading frames 5, 6, and 7 may be related to the exacerbation of clinical disease after an experimental challenge.

    PubMed

    Díaz, Ivan; Ganges, Llilianne; Galindo-Cardiel, Iván; Tarradas, Joan; Alvarez, Belén; Lorca-Oró, Cristina; Pujols, Joan; Gimeno, Mariona; Darwich, Laila; Domingo, Mariano; Domínguez, Javier; Mateu, Enric

    2013-02-01

    Pigs were immunized with DNA plasmids containing different open reading frames (ORFs) of a porcine reproductive and respiratory syndrome virus (PRRSV) genotype I strain. One group was injected with three inoculations of ORF7, a second group was immunized with three inoculations of plasmids containing ORF5 and ORF6, and a third group was kept as controls. Later, +21 days after the last inoculation, animals were challenged with the homologous strain. After the challenge, PRRSV-specific interferon (IFN)-γ-secreting cells and anti-PRRSV IgG antibodies developed faster in DNA vaccinated pigs (p<0.05). However, DNA-immunized pigs showed an exacerbation of the disease compared to the unvaccinated challenged pigs. The data suggest that previous immunization with DNA vaccines against glycoprotein 5 and/or matrix protein of PRRSV, as well as nucleoprotein but to a lesser degree, could result in an exacerbation of the clinical course in terms of fever upon challenge. PMID:23409932

  5. Clinical trial in healthy malaria-naïve adults to evaluate the safety, tolerability, immunogenicity and efficacy of MuStDO5, a five-gene, sporozoite/hepatic stage Plasmodium falciparum DNA vaccine combined with escalating dose human GM-CSF DNA

    PubMed Central

    Richie, Thomas L.; Charoenvit, Yupin; Wang, Ruobing; Epstein, Judith E.; Hedstrom, Richard C.; Kumar, Sanjai; Luke, Thomas C.; Freilich, Daniel A.; Aguiar, Joao C.; Sacci, Jr., John B.; Sedegah, Martha; Nosek, Jr., Ronald A.; De La Vega, Patricia; Berzins, Mara P.; Majam, Victoria F.; Abot, Esteban N.; Ganeshan, Harini; Richie, Nancy O.; Banania, Jo Glenna; Baraceros, Maria Fe B.; Geter, Tanya G.; Mere, Robin; Bebris, Lolita; Limbach, Keith; Hickey, Bradley W.; Lanar, David E.; Ng, Jennifer; Shi, Meng; Hobart, Peter M.; Norman, Jon A.; Soisson, Lorraine A.; Hollingdale, Michael R.; Rogers, William O.; Doolan, Denise L.; Hoffman, Stephen L.

    2012-01-01

    When introduced in the 1990s, immunization with DNA plasmids was considered potentially revolutionary for vaccine development, particularly for vaccines intended to induce protective CD8 T cell responses against multiple antigens. We conducted, in 1997−1998, the first clinical trial in healthy humans of a DNA vaccine, a single plasmid encoding Plasmodium falciparum circumsporozoite protein (PfCSP), as an initial step toward developing a multi-antigen malaria vaccine targeting the liver stages of the parasite. As the next step, we conducted in 2000–2001 a clinical trial of a five-plasmid mixture called MuStDO5 encoding pre-erythrocytic antigens PfCSP, PfSSP2/TRAP, PfEXP1, PfLSA1 and PfLSA3. Thirty-two, malaria-naïve, adult volunteers were enrolled sequentially into four cohorts receiving a mixture of 500 μg of each plasmid plus escalating doses (0, 20, 100 or 500 μg) of a sixth plasmid encoding human granulocyte macrophage-colony stimulating factor (hGM-CSF). Three doses of each formulation were administered intramuscularly by needle-less jet injection at 0, 4 and 8 weeks, and each cohort had controlled human malaria infection administered by five mosquito bites 18 d later. The vaccine was safe and well-tolerated, inducing moderate antigen-specific, MHC-restricted T cell interferon-γ responses but no antibodies. Although no volunteers were protected, T cell responses were boosted post malaria challenge. This trial demonstrated the MuStDO5 DNA and hGM-CSF plasmids to be safe and modestly immunogenic for T cell responses. It also laid the foundation for priming with DNA plasmids and boosting with recombinant viruses, an approach known for nearly 15 y to enhance the immunogenicity and protective efficacy of DNA vaccines. PMID:23151451

  6. Intralymphatic immunization enhances DNA vaccination

    NASA Astrophysics Data System (ADS)

    Maloy, Kevin J.; Erdmann, Iris; Basch, Veronique; Sierro, Sophie; Kramps, Thomas A.; Zinkernagel, Rolf M.; Oehen, Stefan; Kündig, Thomas M.

    2001-03-01

    Although DNA vaccines have been shown to elicit potent immune responses in animal models, initial clinical trials in humans have been disappointing, highlighting a need to optimize their immunogenicity. Naked DNA vaccines are usually administered either i.m. or intradermally. The current study shows that immunization with naked DNA by direct injection into a peripheral lymph node enhances immunogenicity by 100- to 1,000-fold, inducing strong and biologically relevant CD8+ cytotoxic T lymphocyte responses. Because injection directly into a lymph node is a rapid and easy procedure in humans, these results have important clinical implications for DNA vaccination.

  7. Comp Plan: A computer program to generate dose and radiobiological metrics from dose-volume histogram files

    SciTech Connect

    Holloway, Lois Charlotte; Miller, Julie-Anne; Kumar, Shivani; Whelan, Brendan M.; Vinod, Shalini K.

    2012-10-01

    Treatment planning studies often require the calculation of a large number of dose and radiobiological metrics. To streamline these calculations, a computer program called Comp Plan was developed using MATLAB. Comp Plan calculates common metrics, including equivalent uniform dose, tumor control probability, and normal tissue complication probability from dose-volume histogram data. The dose and radiobiological metrics can be calculated for the original data or for an adjusted fraction size using the linear quadratic model. A homogeneous boost dose can be added to a given structure if desired. The final output is written to an Excel file in a format convenient for further statistical analysis. Comp Plan was verified by independent calculations. A lung treatment planning study comparing 45 plans for 7 structures using up to 6 metrics for each structure was successfully analyzed within approximately 5 minutes with Comp Plan. The code is freely available from the authors on request.

  8. A fast underwater optical image segmentation algorithm based on a histogram weighted fuzzy c-means improved by PSO

    NASA Astrophysics Data System (ADS)

    Wang, Shilong; Xu, Yuru; Pang, Yongjie

    2011-03-01

    The S/N of an underwater image is low and has a fuzzy edge. If using traditional methods to process it directly, the result is not satisfying. Though the traditional fuzzy C-means algorithm can sometimes divide the image into object and background, its time-consuming computation is often an obstacle. The mission of the vision system of an autonomous underwater vehicle (AUV) is to rapidly and exactly deal with the information about the object in a complex environment for the AUV to use the obtained result to execute the next task. So, by using the statistical characteristics of the gray image histogram, a fast and effective fuzzy C-means underwater image segmentation algorithm was presented. With the weighted histogram modifying the fuzzy membership, the above algorithm can not only cut down on a large amount of data processing and storage during the computation process compared with the traditional algorithm, so as to speed up the efficiency of the segmentation, but also improve the quality of underwater image segmentation. Finally, particle swarm optimization (PSO) described by the sine function was introduced to the algorithm mentioned above. It made up for the shortcomings that the FCM algorithm can not get the global optimal solution. Thus, on the one hand, it considers the global impact and achieves the local optimal solution, and on the other hand, further greatly increases the computing speed. Experimental results indicate that the novel algorithm can reach a better segmentation quality and the processing time of each image is reduced. They enhance efficiency and satisfy the requirements of a highly effective, real-time AUV.

  9. Modeling the dark current histogram induced by gold contamination in complementary-metal-oxide-semiconductor image sensors

    SciTech Connect

    Domengie, F. Morin, P.; Bauza, D.

    2015-07-14

    We propose a model for dark current induced by metallic contamination in a CMOS image sensor. Based on Shockley-Read-Hall kinetics, the expression of dark current proposed accounts for the electric field enhanced emission factor due to the Poole-Frenkel barrier lowering and phonon-assisted tunneling mechanisms. To that aim, we considered the distribution of the electric field magnitude and metal atoms in the depth of the pixel. Poisson statistics were used to estimate the random distribution of metal atoms in each pixel for a given contamination dose. Then, we performed a Monte-Carlo-based simulation for each pixel to set the number of metal atoms the pixel contained and the enhancement factor each atom underwent, and obtained a histogram of the number of pixels versus dark current for the full sensor. Excellent agreement with the dark current histogram measured on an ion-implanted gold-contaminated imager has been achieved, in particular, for the description of the distribution tails due to the pixel regions in which the contaminant atoms undergo a large electric field. The agreement remains very good when increasing the temperature by 15 °C. We demonstrated that the amplification of the dark current generated for the typical electric fields encountered in the CMOS image sensors, which depends on the nature of the metal contaminant, may become very large at high electric field. The electron and hole emissions and the resulting enhancement factor are described as a function of the trap characteristics, electric field, and temperature.

  10. Identification of invasive fungal diseases in immunocompromised patients by combining an Aspergillus specific PCR with a multifungal DNA-microarray from primary clinical samples.

    PubMed

    Boch, T; Reinwald, M; Postina, P; Cornely, O A; Vehreschild, J J; Heußel, C P; Heinz, W J; Hoenigl, M; Eigl, S; Lehrnbecher, T; Hahn, J; Claus, B; Lauten, M; Egerer, G; Müller, M C; Will, S; Merker, N; Hofmann, W-K; Buchheidt, D; Spiess, B

    2015-12-01

    The increasing incidence of invasive fungal diseases (IFD), most of all invasive aspergillosis (IA) in immunocompromised patients emphasises the need to improve the diagnostic tools for detection of fungal pathogens. We investigated the diagnostic performance of a multifungal DNA-microarray detecting 15 different fungi [Aspergillus, Candida, Fusarium, Mucor, Rhizopus, Scedosporium and Trichosporon species (spp.)] in addition to an Aspergillus specific polymerase chain reaction (PCR) assay. Biopsies, bronchoalveolar lavage and peripheral blood samples of 133 immunocompromised patients (pts) were investigated by a multifungal DNA-microarray as well as a nested Aspergillus specific PCR assay. Patients had proven (n = 18), probable (n = 29), possible (n = 48) and no IFD (n = 38) and were mostly under antifungal therapy at the time of sampling. The results were compared to culture, histopathology, imaging and serology, respectively. For the non-Aspergillus IFD the microarray analysis yielded in all samples a sensitivity of 64% and a specificity of 80%. Best results for the detection of all IFD were achieved by combining DNA-microarray and Aspergillus specific PCR in biopsy samples (sensitivity 79%; specificity 71%). The molecular assays in combination identify genomic DNA of fungal pathogens and may improve identification of causative pathogens of IFD and help overcoming the diagnostic uncertainty of culture and/or histopathology findings, even during antifungal therapy. PMID:26497302

  11. Downregulation of the cancer susceptibility protein WRAP53β in epithelial ovarian cancer leads to defective DNA repair and poor clinical outcome

    PubMed Central

    Hedström, E; Pederiva, C; Farnebo, J; Nodin, B; Jirström, K; Brennan, D J; Farnebo, M

    2015-01-01

    Alterations in the scaffold protein WRAP53β have previously been linked to carcinogenesis and, in particular, associated with an increased risk for epithelial ovarian cancer. Here, we investigated the pathogenic impact and prognostic significance of WRAP53β in connection with epithelial ovarian cancer and examined the underlying mechanisms. We find that reduced expression of WRAP53β in ovarian tumors correlated with attenuated DNA damage response and poor patient survival. Furthermore, in ovarian cancer cell lines, WRAP53β was rapidly recruited to DNA double-strand breaks, where it orchestrated the recruitment of repair factors involved in homologous recombination and non-homologous end joining, including RNF168, 53BP1, BRCA1 and RAD51. Mechanistically, WRAP53β accomplishes this by facilitating the necessary ubiquitinylation at DNA breaks. Finally, we demonstrate that loss of WRAP53β significantly impairs the repair of DNA double-strand breaks, resulting in their accumulation. Our findings establish WRAP53β as a regulator of homologous recombination and non-homologous end joining repair in ovarian cancer cells, suggesting that loss of this protein contributes to the development and/or progression of ovarian tumors. Moreover, our current observations identify the nuclear levels of WRAP53β as a promising biomarker for the survival of patients with ovarian cancer. PMID:26426684

  12. Phase I Randomized Clinical Trial of VRC DNA and rAd5 HIV-1 Vaccine Delivery by Intramuscular (IM), Subcutaneous (SC) and Intradermal (ID) Administration (VRC 011)

    PubMed Central

    Enama, Mary E.; Ledgerwood, Julie E.; Novik, Laura; Nason, Martha C.; Gordon, Ingelise J.; Holman, LaSonji; Bailer, Robert T.; Roederer, Mario; Koup, Richard A.; Mascola, John R.; Nabel, Gary J.; Graham, Barney S.

    2014-01-01

    Background Phase 1 evaluation of the VRC HIV DNA and rAd5 vaccines delivered intramuscularly (IM) supported proceeding to a Phase 2 b efficacy study. Here we report comparison of the IM, subcutaneous (SC) and intradermal (ID) routes of administration. Methods Sixty subjects were randomized to 6 schedules to evaluate the IM, SC or ID route for prime injections. Three schedules included DNA primes (Wks 0,4,8) and 3 schedules included rAd5 prime (Wk0); all included rAd5 IM boost (Wk24). DNA vaccine dosage was 4 mg IM or SC, but 0.4 mg ID, while all rAd5 vaccinations were 1010 PU. All injections were administered by needle and syringe. Results Overall, 27/30 subjects completed 3 DNA primes; 30/30 subjects completed rAd5 primes. Mild local pruritus (itchiness), superficial skin lesions and injection site nodules were associated with ID and SC, but not IM injections. All routes induced T-cell and antibody immune responses after rAd5 boosting. Overall, >95% had Env antibody and >80% had Env T-cell responses. Conclusions The pattern of local reactogenicity following ID and SC injections differed from IM injections but all routes were well-tolerated. There was no evidence of an immunogenicity advantage following SC or ID delivery, supporting IM delivery as the preferred route of administration. Trial Registration Clinicaltrials.gov NCT00321061 PMID:24621858

  13. Comparative clinical sample preparation of DNA and RNA viral nucleic acids for a commercial deep sequencing system (Illumina MiSeq(®)).

    PubMed

    Ullmann, Leila Sabrina; de Camargo Tozato, Claudia; Malossi, Camila Dantas; da Cruz, Tais Fukuta; Cavalcante, Raíssa Vasconcelos; Kurissio, Jacqueline Kazue; Cagnini, Didier Quevedo; Rodrigues, Marianna Vaz; Biondo, Alexander Welker; Araujo, João Pessoa

    2015-08-01

    Sequence-independent methods for viral discovery have been widely used for whole genome sequencing of viruses. Different protocols for viral enrichment, library preparation and sequencing have increasingly been more available and at lower costs. However, no study to date has focused on optimization of viral sample preparation for commercial deep sequencing. Accordingly, the aim of the present study was to evaluate an In-House enzymatic protocol for double-stranded DNA (dsDNA) synthesis and also compare the use of a commercially available kit protocol (Nextera XT, Illumina Inc, San Diego, CA, USA) and its combination with a library quantitation kit (Kapa, Kapa Biosystems, Wilmington, MA, USA) for deep sequencing (Illumina Miseq). Two RNA viruses (canine distemper virus and dengue virus) and one ssDNA virus (porcine circovirus type 2) were tested with the optimized protocols. The tested method for dsDNA synthesis has shown satisfactory results and may be used in laboratory setting, particularly when enzymes are already available. Library preparation combining commercial kits (Nextera XT and Kapa) has yielded more reads and genome coverage, probably due to a lack of small fragment recovering at the normalization step of Nextera XT. In addition, libraries may be diluted or concentrated to provide increase on genome coverage with Kapa quantitation. PMID:25901649

  14. Efficient Sleeping Beauty DNA Transposition From DNA Minicircles

    PubMed Central

    Sharma, Nynne; Cai, Yujia; Bak, Rasmus O; Jakobsen, Martin R; Schrøder, Lisbeth Dahl; Mikkelsen, Jacob Giehm

    2013-01-01

    DNA transposon-based vectors have emerged as new potential delivery tools in therapeutic gene transfer. Such vectors are now showing promise in hematopoietic stem cells and primary human T cells, and clinical trials with transposon-engineered cells are on the way. However, the use of plasmid DNA as a carrier of the vector raises safety concerns due to the undesirable administration of bacterial sequences. To optimize vectors based on the Sleeping Beauty (SB) DNA transposon for clinical use, we examine here SB transposition from DNA minicircles (MCs) devoid of the bacterial plasmid backbone. Potent DNA transposition, directed by the hyperactive SB100X transposase, is demonstrated from MC donors, and the stable transfection rate is significantly enhanced by expressing the SB100X transposase from MCs. The stable transfection rate is inversely related to the size of circular donor, suggesting that a MC-based SB transposition system benefits primarily from an increased cellular uptake and/or enhanced expression which can be observed with DNA MCs. DNA transposon and transposase MCs are easily produced, are favorable in size, do not carry irrelevant DNA, and are robust substrates for DNA transposition. In accordance, DNA MCs should become a standard source of DNA transposons not only in therapeutic settings but also in the daily use of the SB system. PMID:23443502

  15. Development and evaluation of convergent and accelerated penalized SPECT image reconstruction methods for improved dose–volume histogram estimation in radiopharmaceutical therapy

    PubMed Central

    Cheng, Lishui; Hobbs, Robert F.; Sgouros, George; Frey, Eric C.

    2014-01-01

    Purpose: Three-dimensional (3D) dosimetry has the potential to provide better prediction of response of normal tissues and tumors and is based on 3D estimates of the activity distribution in the patient obtained from emission tomography. Dose–volume histograms (DVHs) are an important summary measure of 3D dosimetry and a widely used tool for treatment planning in radiation therapy. Accurate estimates of the radioactivity distribution in space and time are desirable for accurate 3D dosimetry. The purpose of this work was to develop and demonstrate the potential of penalized SPECT image reconstruction methods to improve DVHs estimates obtained from 3D dosimetry methods. Methods: The authors developed penalized image reconstruction methods, using maximum a posteriori (MAP) formalism, which intrinsically incorporate regularization in order to control noise and, unlike linear filters, are designed to retain sharp edges. Two priors were studied: one is a 3D hyperbolic prior, termed single-time MAP (STMAP), and the second is a 4D hyperbolic prior, termed cross-time MAP (CTMAP), using both the spatial and temporal information to control noise. The CTMAP method assumed perfect registration between the estimated activity distributions and projection datasets from the different time points. Accelerated and convergent algorithms were derived and implemented. A modified NURBS-based cardiac-torso phantom with a multicompartment kidney model and organ activities and parameters derived from clinical studies were used in a Monte Carlo simulation study to evaluate the methods. Cumulative dose-rate volume histograms (CDRVHs) and cumulative DVHs (CDVHs) obtained from the phantom and from SPECT images reconstructed with both the penalized algorithms and OS-EM were calculated and compared both qualitatively and quantitatively. The STMAP method was applied to patient data and CDRVHs obtained with STMAP and OS-EM were compared qualitatively. Results: The results showed that the

  16. DNA vaccine for cancer immunotherapy

    PubMed Central

    Yang, Benjamin; Jeang, Jessica; Yang, Andrew; Wu, T C; Hung, Chien-Fu

    2015-01-01

    DNA vaccination has emerged as an attractive immunotherapeutic approach against cancer due to its simplicity, stability, and safety. Results from numerous clinical trials have demonstrated that DNA vaccines are well tolerated by patients and do not trigger major adverse effects. DNA vaccines are also very cost effective and can be administered repeatedly for long-term protection. Despite all the practical advantages, DNA vaccines face challenges in inducing potent antigen specific cellular immune responses as a result of immune tolerance against endogenous self-antigens in tumors. Strategies to enhance immunogenicity of DNA vaccines against self-antigens have been investigated including encoding of xenogeneic versions of antigens, fusion of antigens to molecules that activate T cells or trigger associative recognition, priming with DNA vectors followed by boosting with viral vector, and utilization of immunomodulatory molecules. This review will focus on discussing strategies that circumvent immune tolerance and provide updates on findings from recent clinical trials. PMID:25625927

  17. Combined low initial DNA damage and high radiation-induced apoptosis confers clinical resistance to long-term toxicity in breast cancer patients treated with high-dose radiotherapy

    PubMed Central

    2011-01-01

    Background Either higher levels of initial DNA damage or lower levels of radiation-induced apoptosis in peripheral blood lymphocytes have been associated to increased risk for develop late radiation-induced toxicity. It has been recently published that these two predictive tests are inversely related. The aim of the present study was to investigate the combined role of both tests in relation to clinical radiation-induced toxicity in a set of breast cancer patients treated with high dose hyperfractionated radical radiotherapy. Methods Peripheral blood lymphocytes were taken from 26 consecutive patients with locally advanced breast carcinoma treated with high-dose hyperfractioned radical radiotherapy. Acute and late cutaneous and subcutaneous toxicity was evaluated using the Radiation Therapy Oncology Group morbidity scoring schema. The mean follow-up of survivors (n = 13) was 197.23 months. Radiosensitivity of lymphocytes was quantified as the initial number of DNA double-strand breaks induced per Gy and per DNA unit (200 Mbp). Radiation-induced apoptosis (RIA) at 1, 2 and 8 Gy was measured by flow cytometry using annexin V/propidium iodide. Results Mean DSB/Gy/DNA unit obtained was 1.70 ± 0.83 (range 0.63-4.08; median, 1.46). Radiation-induced apoptosis increased with radiation dose (median 12.36, 17.79 and 24.83 for 1, 2, and 8 Gy respectively). We observed that those "expected resistant patients" (DSB values lower than 1.78 DSB/Gy per 200 Mbp and RIA values over 9.58, 14.40 or 24.83 for 1, 2 and 8 Gy respectively) were at low risk of suffer severe subcutaneous late toxicity (HR 0.223, 95%CI 0.073-0.678, P = 0.008; HR 0.206, 95%CI 0.063-0.677, P = 0.009; HR 0.239, 95%CI 0.062-0.929, P = 0.039, for RIA at 1, 2 and 8 Gy respectively) in multivariate analysis. Conclusions A radiation-resistant profile is proposed, where those patients who presented lower levels of initial DNA damage and higher levels of radiation induced apoptosis were at low risk of suffer severe

  18. Dynamics of interaction between complement-fixing antibody/dsDNA immune complexes and erythrocytes. In vitro studies and potential general applications to clinical immune complex testing

    SciTech Connect

    Taylor, R.P.; Horgan, C.; Hooper, M.; Burge, J.

    1985-01-01

    Soluble antibody//sub 3/H-double-stranded PM2 DNA (dsDNA) immune complexes were briefly opsonized with complement and then allowed to bind to human erythrocytes (via complement receptors). The cells were washed and subsequently a volume of autologous blood in a variety of media was added, and the release of the bound immune complexes from the erythrocytes was studied as a function of temperature and time. After 1-2 h, the majority of the bound immune complexes were not released into the serum during blood clotting at either 37 degrees C or room temperature, but there was a considerably greater release of the immune complexes into the plasma of blood that was anticoagulated with EDTA. Similar results were obtained using various conditions of opsonization and also using complexes that contained lower molecular weight dsDNA. Thus, the kinetics of release of these antibody/dsDNA immune complexes differed substantially from the kinetics of release of antibody/bovine serum albumin complexes that was reported by others. Studies using the solution phase C1q immune complex binding assay confirmed that in approximately half of the SLE samples that were positive for immune complexes, there was a significantly higher level of detectable immune complexes in plasma vs. serum. Freshly drawn erythrocytes from some SLE patients exhibiting this plasma/serum discrepancy had IgG antigen on their surface that was released by incubation in EDTA plasma. Thus, the higher levels of immune complexes observed in EDTA plasma vs. serum using the C1q assay may often reflect the existence of immune complexes circulating in vivo bound to erythrocytes.

  19. Evaluation of breast cancer using intravoxel incoherent motion (IVIM) histogram analysis: comparison with malignant status, histological subtype, and molecular prognostic factors

    PubMed Central

    Cho, Gene Young; Moy, Linda; Kim, Sungheon G.; Baete, Steven H.; Moccaldi, Melanie; Babb, James S.; Sodickson, Daniel K.; Sigmund, Eric E.

    2016-01-01

    Purpose To examine heterogeneous breast cancer through intravoxel incoherent motion (IVIM) histogram analysis. Materials and methods This HIPAA-compliant, IRB-approved retrospective study included 62 patients (age 48.44±11.14 years, 50 malignant lesions and 12 benign) who underwent contrast-enhanced 3 T breast MRI and diffusion-weighted imaging. Apparent diffusion coefficient (ADC) and IVIM biomarkers of tissue diffusivity (Dt), perfusion fraction (fp), and pseudo-diffusivity (Dp) were calculated using voxel-based analysis for the whole lesion volume. Histogram analysis was performed to quantify tumour heterogeneity. Comparisons were made using Mann–Whitney tests between benign/malignant status, histological subtype, and molecular prognostic factor status while Spearman’s rank correlation was used to characterize the association between imaging biomarkers and prognostic factor expression. Results The average values of the ADC and IVIM biomarkers, Dt and fp, showed significant differences between benign and malignant lesions. Additional significant differences were found in the histogram parameters among tumour subtypes and molecular prognostic factor status. IVIM histogram metrics, particularly fp and Dp, showed significant correlation with hormonal factor expression. Conclusion Advanced diffusion imaging biomarkers show relationships with molecular prognostic factors and breast cancer malignancy. This analysis reveals novel diagnostic metrics that may explain some of the observed variability in treatment response among breast cancer patients. PMID:26615557

  20. Mitochondrial DNA.

    ERIC Educational Resources Information Center

    Wright, Russell G.; Bottino, Paul J.

    1986-01-01

    Provides background information for teachers on mitochondrial DNA, pointing out that it may have once been a free-living organism. Includes a ready-to-duplicate exercise titled "Using Microchondrial DNA to Measure Evolutionary Distance." (JN)

  1. Development and clinical validation of a real-time PCR assay for PITX2 DNA methylation to predict prostate-specific antigen recurrence in prostate cancer patients following radical prostatectomy.

    PubMed

    Dietrich, Dimo; Hasinger, Oliver; Bañez, Lionel L; Sun, Leon; van Leenders, Geert J; Wheeler, Thomas M; Bangma, Chris H; Wernert, Nicolas; Perner, Sven; Freedland, Stephen J; Corman, John M; Ittmann, Michael M; Lark, Amy L; Madden, John F; Hartmann, Arndt; Schatz, Philipp; Kristiansen, Glen

    2013-03-01

    Prostate cancer is the most common cancer among men. The prospective discrimination of aggressive and clinically insignificant tumors still poses a significant and, as yet, unsolved problem. PITX2 DNA methylation is a strong prognostic biomarker in prostate cancer. Recently, a diagnostic microarray for prostate cancer prognosis based on PITX2 methylation has been developed and validated. Because this microarray requires nonstandard laboratory equipment, its use in a diagnostic setting is limited. This study aimed to develop and validate an alternative quantitative real-time PCR assay for measuring PITX2 methylation that can easily be established in clinical laboratories, thereby facilitating the implementation of this biomarker in clinical practice. A methylation cut-off for patient stratification was established in a training cohort (n = 157) and validated in an independent test set (n = 523) of men treated with radical prostatectomy. In univariate Cox proportional hazards analysis, PITX2 hypermethylation was a significant predictor for biochemical recurrence (P < 0.001, hazard ratio = 2.614). Moreover, PITX2 hypermethylation added significant prognostic information (P = 0.003, hazard ratio = 1.814) to the Gleason score, pathological T stage, prostate-specific antigen, and surgical margins in a multivariate analysis. The clinical performance was particularly high in patients at intermediate risk (Gleason score of 7) and in samples containing high tumor cell content. This assay might aid in risk stratification and support the decision-making process when determining whether a patient might benefit from adjuvant treatment after radical prostatectomy. PMID:23266319

  2. Changes in Fat Mitochondrial DNA and Function in Subjects Randomized to Abacavir-Lamivudine or Tenofovir DF–Emtricitabine With Atazanavir-Ritonavir or Efavirenz: AIDS Clinical Trials Group Study A5224s, Substudy of A5202

    PubMed Central

    McComsey, Grace A.; Daar, Eric S.; O'Riordan, MaryAnn; Collier, Ann C.; Kosmiski, Lisa; Santana, Jorge L.; Fichtenbaum, Carl J.; Fink, Heidi; Sax, Paul E.; Libutti, Daniel E.; Gerschenson, Mariana

    2013-01-01

    Background. The effect of nonthymidine nucleoside reverse-transcriptase inhibitors (NRTIs) on fat mitochondrial DNA (mtDNA) content and function is unclear. Methods. A5202 randomized antiretroviral therapy–naive human immunodeficiency virus–infected subjects to abacavir-lamivudine (ABC/3TC) versus tenofovir DF–emtricitabine (TDF/FTC) with efavirenz (EFV) or atazanavir-ritonavir (ATV/r). A5224s, substudy of A5202, enrolled 269 subjects with fat measurements by dual-energy x-ray absorptiometry and computed tomography. A subset of subjects underwent fat biopsies at baseline and week 96 for mtDNA content (real-time polymerase chain reaction) and oxidative phosphorylation nicotinamide adenine dinucleotide (reduced) dehydrogenase (complex I) and cytochrome c oxidase (complex IV) activity levels (immunoassays). Intent-to-treat analyses were performed using analysis of variance and paired t tests. Results. Fifty-six subjects (87% male; median age, 39 years) were included; their median body mass index, CD4 cell count, and fat mtDNA level were 26 kg/m2, 227 cells/μL, and 1197 copies/cell, respectively. Fat mtDNA content decreased within the ABC/3TC and TDF/FTC groups (combining EFV and ATV/r arms; median change, −341 [interquartile range, −848 to 190; P = .03] and −400 [−661 to −221; P < .001] copies/cell, respectively), but these changes did not differ significantly between the 2 groups (P = .57). Complex I and IV activity decreased significantly in the TDF/FTC group (median change, −12.45 [interquartile range, −24.70 to 2.90; P = .003] and −8.25 [−13.90 to −1.30; P < .001], optical density × 103/µg, respectively) but not the ABC/3TC group. Differences between the ABC/3TC and TDF/FTC groups were significant for complex I (P = .03). Conclusions. ABC/3TC and TDF/FTC significantly and similarly decreased fat mtDNA content, but only TDF/FTC decreased complex I and complex IV activity levels. Clinical Trials Registration. NCT00118898. PMID

  3. Clinical performance of multiplex high-risk e6 mrna expression in comparison with hpv dna subtypes for the identification of women at risk of cervical cancer.

    PubMed

    Ho, Chih-Ming; Pan, Kui-You; Chen, Yun-Yuan; Huang, Chia-Yen; Chen, Yu-Li; Chang, Shwu-Fen

    2015-08-01

    We compared multiplex E6 messenger ribonucleic acid (mRNA) tests using real-time quantitative reverse transcriptase polymerase chain reactions (PCR) with human papillomavirus (HPV) DNA subtypes using a MY11/GP6+ PCR-based reverse-blot assay to identify cervical intraepithelial neoplasias of grade 2 or worse (CIN2+). In total, 684 women were studied, of whom 377 (55%) were diagnosed with CIN2+ histologically. The specificity of HPV mRNA to predict histological CIN2+ was higher than that of HPV DNA (81.3% vs. 44.2%). The odds ratios (ORs) to predict histological CIN2+ in women with positive for type 16, 18, 31, and 45 E6 mRNA or by HPV DNA detection were 7.1 (95% confidence interval [CI] 3.9-13.1) and 2.5 (95%CI 1.9-3.5), respectively, compared to those with negative for E6 mRNA or HPV DNA. The OR to predict histological CIN2+ in women with a cytological grade DNA positive triage, the OR to predict histological CIN2+ in women with a cytological grade

  4. DNA Banking

    SciTech Connect

    Reilly, P.R. )

    1992-11-01

    The author is involved in the ethical, legal, and social issues of banking of DNA and data from DNA analysis. In his attempt to determine the extent of DNA banking in the U.S., the author surveyed some commercial companies performing DNA banking services. This article summarizes the results of that survey, with special emphasis on the procedures the companies use to protect the privacy of individuals. 4 refs.

  5. BEDVH--A method for evaluating biologically effective dose volume histograms: Application to eye plaque brachytherapy implants

    SciTech Connect

    Gagne, Nolan L.; Leonard, Kara L.; Huber, Kathryn E.; Mignano, John E.; Duker, Jay S.; Laver, Nora V.; Rivard, Mark J.

    2012-02-15

    Purpose: A method is introduced to examine the influence of implant duration T, radionuclide, and radiobiological parameters on the biologically effective dose (BED) throughout the entire volume of regions of interest for episcleral brachytherapy using available radionuclides. This method is employed to evaluate a particular eye plaque brachytherapy implant in a radiobiological context. Methods: A reference eye geometry and 16 mm COMS eye plaque loaded with {sup 103}Pd, {sup 125}I, or {sup 131}Cs sources were examined with dose distributions accounting for plaque heterogeneities. For a standardized 7 day implant, doses to 90% of the tumor volume ( {sub TUMOR}D{sub 90}) and 10% of the organ at risk volumes ( {sub OAR}D{sub 10}) were calculated. The BED equation from Dale and Jones and published {alpha}/{beta} and {mu} parameters were incorporated with dose volume histograms (DVHs) for various T values such as T = 7 days (i.e., {sub TUMOR} {sup 7}BED{sub 10} and {sub OAR} {sup 7}BED{sub 10}). By calculating BED throughout the volumes, biologically effective dose volume histograms (BEDVHs) were developed for tumor and OARs. Influence of T, radionuclide choice, and radiobiological parameters on {sub TUMOR}BEDVH and {sub OAR}BEDVH were examined. The nominal dose was scaled for shorter implants to achieve biological equivalence. Results: {sub TUMOR}D{sub 90} values were 102, 112, and 110 Gy for {sup 103}Pd, {sup 125}I, and {sup 131}Cs, respectively. Corresponding {sub TUMOR} {sup 7}BED{sub 10} values were 124, 140, and 138 Gy, respectively. As T decreased from 7 to 0.01 days, the isobiologically effective prescription dose decreased by a factor of three. As expected, {sub TUMOR} {sup 7}BEDVH did not significantly change as a function of radionuclide half-life but varied by 10% due to radionuclide dose distribution. Variations in reported radiobiological parameters caused {sub TUMOR} {sup 7}BED{sub 10} to deviate by up to 46%. Over the range of {sub OAR

  6. Dna Sequencing

    DOEpatents

    Tabor, Stanley; Richardson, Charles C.

    1995-04-25

    A method for sequencing a strand of DNA, including the steps off: providing the strand of DNA; annealing the strand with a primer able to hybridize to the strand to give an annealed mixture; incubating the mixture with four deoxyribonucleoside triphosphates, a DNA polymerase, and at least three deoxyribonucleoside triphosphates in different amounts, under conditions in favoring primer extension to form nucleic acid fragments complementory to the DNA to be sequenced; labelling the nucleic and fragments; separating them and determining the position of the deoxyribonucleoside triphosphates by differences in the intensity of the labels, thereby to determine the DNA sequence.

  7. Facilitation between extensor carpi radialis and pronator teres in humans: a study using a post-stimulus time histogram method.

    PubMed

    Nakano, Haruki; Miyasaka, Takuji; Ogino, Toshihiko; Naito, Akira

    2014-12-01

    Group I muscle afferents modulate the excitability of motor neurons through excitatory and inhibitory spinal reflexes. Spinal reflex relationships between various muscle pairs are well described in experimental animals but not in the human upper limb, which exhibits a fine control of movement. In the present study, spinal reflexes between the extensor carpi radialis (ECR) and pronator teres (PT) muscles were examined in healthy human subjects using a post-stimulus time histogram method. Electrical stimulation of low-threshold afferents of ECR nerves increased the motor neuron excitability in 31 of 76 PT motor units (MUs) in all eight subjects tested, while stimulation of low-threshold afferents of PT nerves increased the motor neuron excitability in 36 of 102 ECR MUs in all 10 subjects. The estimated central synaptic delay was almost equivalent to that of homonymous facilitation. Mechanical stimulation (MS) of ECR facilitated 16 of 30 PT MUs in all five subjects tested, while MS of PT facilitated 17 of 30 ECR MUs in all six subjects. These results suggest excitatory reflex (facilitation) between PT and ECR. Group I afferents should mediate the facilitation through a monosynaptic path. PMID:25026240

  8. Highly sensitive image-derived indices of water-stressed plants using hyperspectral imaging in SWIR and histogram analysis

    PubMed Central

    Kim, David M.; Zhang, Hairong; Zhou, Haiying; Du, Tommy; Wu, Qian; Mockler, Todd C.; Berezin, Mikhail Y.

    2015-01-01

    The optical signature of leaves is an important monitoring and predictive parameter for a variety of biotic and abiotic stresses, including drought. Such signatures derived from spectroscopic measurements provide vegetation indices – a quantitative method for assessing plant health. However, the commonly used metrics suffer from low sensitivity. Relatively small changes in water content in moderately stressed plants demand high-contrast imaging to distinguish affected plants. We present a new approach in deriving sensitive indices using hyperspectral imaging in a short-wave infrared range from 800 nm to 1600 nm. Our method, based on high spectral resolution (1.56 nm) instrumentation and image processing algorithms (quantitative histogram analysis), enables us to distinguish a moderate water stress equivalent of 20% relative water content (RWC). The identified image-derived indices 15XX nm/14XX nm (i.e. 1529 nm/1416 nm) were superior to common vegetation indices, such as WBI, MSI, and NDWI, with significantly better sensitivity, enabling early diagnostics of plant health. PMID:26531782

  9. Usefulness of histogram analysis of spatial frequency components for exploring the similarity and bilateral asymmetry in mammograms

    NASA Astrophysics Data System (ADS)

    Shiotsuki, Kenshi; Matsunobu, Yusuke; Yabuuchi, Hidetake; Morishita, Junji

    2015-03-01

    The right and left mammograms of a patient are assumed to be bilaterally symmetric for image readings. The detection of asymmetry in bilateral mammograms is a reliable indicator for detecting possible breast abnormalities. The purpose of this study was to examine the potential usefulness of a new method in terms of spatial frequency components for exploration of similarity and abnormality between the right and left mammograms. A total of 98 normal and 119 abnormal cases with calcifications were used for this study. Each case included two mediolateral oblique views. The spatial frequency components were determined from the symmetric regions in the right and left mammograms by Fourier transform. The degrees of conformity between the two spatial frequency components in the right and left mammograms were calculated for the same and different patients. The degrees of conformity were also examined for cases with and without calcifications for the same patient to show if the proposed method was useful for indicating the existence of calcifications or not. The average degrees of conformity and the standard deviations for the same and different patients were 0.911 +/- 0.0165 and 0.857 +/- 0.0328, respectively. The degrees of conformity calculated from abnormal cases (0.836 +/- 0.0906) showed statistically lower values compared with those measured from normal cases (0.911 +/- 0.0165). Our results indicated that histogram analysis of spatial frequency components could be useful as a similarity measure between bilateral mammograms for the same patient and abnormal signs in a mammogram.

  10. Highly sensitive image-derived indices of water-stressed plants using hyperspectral imaging in SWIR and histogram analysis.

    PubMed

    Kim, David M; Zhang, Hairong; Zhou, Haiying; Du, Tommy; Wu, Qian; Mockler, Todd C; Berezin, Mikhail Y

    2015-01-01

    The optical signature of leaves is an important monitoring and predictive parameter for a variety of biotic and abiotic stresses, including drought. Such signatures derived from spectroscopic measurements provide vegetation indices - a quantitative method for assessing plant health. However, the commonly used metrics suffer from low sensitivity. Relatively small changes in water content in moderately stressed plants demand high-contrast imaging to distinguish affected plants. We present a new approach in deriving sensitive indices using hyperspectral imaging in a short-wave infrared range from 800 nm to 1600 nm. Our method, based on high spectral resolution (1.56 nm) instrumentation and image processing algorithms (quantitative histogram analysis), enables us to distinguish a moderate water stress equivalent of 20% relative water content (RWC). The identified image-derived indices 15XX nm/14XX nm (i.e. 1529 nm/1416 nm) were superior to common vegetation indices, such as WBI, MSI, and NDWI, with significantly better sensitivity, enabling early diagnostics of plant health. PMID:26531782

  11. Adaptive block-wise alphabet reduction scheme for lossless compression of images with sparse and locally sparse histograms

    NASA Astrophysics Data System (ADS)

    Masmoudi, Atef; Zouari, Sonia; Ghribi, Abdelaziz

    2015-11-01

    We propose a new adaptive block-wise lossless image compression algorithm, which is based on the so-called alphabet reduction scheme combined with an adaptive arithmetic coding (AC). This new encoding algorithm is particularly efficient for lossless compression of images with sparse and locally sparse histograms. AC is a very efficient technique for lossless data compression and produces a rate that is close to the entropy; however, a compression performance loss occurs when encoding images or blocks with a limited number of active symbols by comparison with the number of symbols in the nominal alphabet, which consists in the amplification of the zero frequency problem. Generally, most methods add one to the frequency count of each symbol from the nominal alphabet, which leads to a statistical model distortion, and therefore reduces the efficiency of the AC. The aim of this work is to overcome this drawback by assigning to each image block the smallest possible set including all the existing symbols called active symbols. This is an alternative of using the nominal alphabet when applying the conventional arithmetic encoders. We show experimentally that the proposed method outperforms several lossless image compression encoders and standards including the conventional arithmetic encoders, JPEG2000, and JPEG-LS.

  12. Vision-based drone flight control and crowd or riot analysis with efficient color histogram based tracking

    NASA Astrophysics Data System (ADS)

    Müller, Thomas; Müller, Markus

    2011-05-01

    Object tracking is a direct or indirect key issue in many different military applications like visual surveillance, automatic visual closed-loop control of UAVs (unmanned aerial vehicles) and PTZ-cameras, or in the field of crowd evaluations in order to detect or analyse a riot emergence. Of course, a high robustness is the most important feature of the underlying tracker, but this is hindered significantly the more the tracker needs to have low calculation times. In the UAV application introduced in this paper the tracker has to be extraordinarily quick. In order to optimize the calculation time and the robustness in combination as far as possible, a highly efficient tracking procedure is presented for the above mentioned application fields which relies on well-known color histograms but uses them in a novel manner. This procedure bases on the calculation of a color weighting vector representing the significances of object colors like a kind of an object's color finger print. Several examples from the above mentioned military applications are shown to demonstrate the practical relevance and the performance of the presented tracking approach.

  13. Highly sensitive image-derived indices of water-stressed plants using hyperspectral imaging in SWIR and histogram analysis

    NASA Astrophysics Data System (ADS)

    Kim, David M.; Zhang, Hairong; Zhou, Haiying; Du, Tommy; Wu, Qian; Mockler, Todd C.; Berezin, Mikhail Y.

    2015-11-01

    The optical signature of leaves is an important monitoring and predictive parameter for a variety of biotic and abiotic stresses, including drought. Such signatures derived from spectroscopic measurements provide vegetation indices - a quantitative method for assessing plant health. However, the commonly used metrics suffer from low sensitivity. Relatively small changes in water content in moderately stressed plants demand high-contrast imaging to distinguish affected plants. We present a new approach in deriving sensitive indices using hyperspectral imaging in a short-wave infrared range from 800 nm to 1600 nm. Our method, based on high spectral resolution (1.56 nm) instrumentation and image processing algorithms (quantitative histogram analysis), enables us to distinguish a moderate water stress equivalent of 20% relative water content (RWC). The identified image-derived indices 15XX nm/14XX nm (i.e. 1529 nm/1416 nm) were superior to common vegetation indices, such as WBI, MSI, and NDWI, with significantly better sensitivity, enabling early diagnostics of plant health.

  14. O(1) time algorithms for computing histogram and Hough transform on a cross-bridge reconfigurable array of processors

    SciTech Connect

    Kao, T.; Horng, S.; Wang, Y.

    1995-04-01

    Instead of using the base-2 number system, we use a base-m number system to represent the numbers used in the proposed algorithms. Such a strategy can be used to design an O(T) time, T = (log(sub m) N) + 1, prefix sum algorithm for a binary sequence with N-bit on a cross-bridge reconfigurable array of processors using N processors, where the data bus is m-bit wide. Then, this basic operation can be used to compute the histogram of an n x n image with G gray-level value in constant time using G x n x n processors, and compute the Hough transform of an image with N edge pixels and n x n parameter space in constant time using n x n x N processors, respectively. This result is better than the previously known results proposed in the literature. Also, the execution time of the proposed algorithms is tunable by the bus bandwidth. 43 refs.

  15. Distinction of deep versus superficial clinical and nonclinical isolates of Trichosporon beigelii by isoenzymes and restriction fragment length polymorphisms of rDNA generated by polymerase chain reaction.

    PubMed Central

    Kemker, B J; Lehmann, P F; Lee, J W; Walsh, T J

    1991-01-01

    Fifteen clinical and environmental strains of Trichosporon beigelii were analyzed for similarities by using morphological features, biochemical profiles based on carbon compound assimilation and uric acid utilization, isoenzyme electrophoresis, and restriction fragment length polymorphisms of a segment of genes coding for rRNA expanded with the polymerase chain reaction. The findings suggest that strains that cause invasive disease are distinct from the superficial and the nonclinical isolates and that isolates from the skin and mucosae represent a number of different organisms, including some environmental forms. The study shows that T. beigelii is a complex of genetically distinct organisms and that more than one type is found in clinical samples. Images PMID:1684798

  16. Simultaneous occurrence of the 11778 (ND4) and the 9438 (COX III) mtDNA mutations in Leber hereditary optic neuropathy: Molecular, biochemical, and clinical findings

    SciTech Connect

    Oostra, R.J.; Bleeker-Wagemakers, E.M.; Zwart, R.

    1995-10-01

    Three mtDNA point mutations at nucleotide position (np) 3460, at np 11778 and at np 14484, are thought to be of primary importance in the pathogenesis of Leber hereditary optic neuropathy (LHON), a maternally inherited disease characterized by subacute central vision loss. These mutations are present in genes coding for subunits of complex I (NADH dehydrogenase) of the respiratory chain, occur exclusively in LHON maternal pedigrees, and have never been reported to occur together. Johns and Neufeld postulated that an mtDNA mutation at np 9438, in the gene coding for one of the subunits (COX III) of complex IV (cytochrome c oxidase), was also of primary importance. Johns and Neufeld (1993) found this mutation, which changed a conserved glycine to a serine, in 5 unrelated LHON probands who did not carry one of the presently known primary mutations, but they did not find it in 400 controls. However, the role of this sequence variant has been questioned in the Journal when it has been found to occur in apparently healthy African and Cuban individuals. Subsequently, Johns et al. described this mutation in two Cuban individuals presenting with optic and peripheral neuropathy. 22 refs., 1 fig., 1 tab.

  17. Late Toxicity After Intensity-Modulated Radiation Therapy for Localized Prostate Cancer: An Exploration of Dose-Volume Histogram Parameters to Limit Genitourinary and Gastrointestinal Toxicity

    SciTech Connect

    Pederson, Aaron W.; Fricano, Janine; Correa, David; Pelizzari, Charles A.; Liauw, Stanley L.

    2012-01-01

    Purpose: To characterize the late genitourinary (GU) and gastrointestinal (GI) toxicity for prostate cancer patients treated with intensity-modulated radiation therapy (IMRT) and propose dose-volume histogram (DVH) guidelines to limit late treatment-related toxicity. Methods and Materials: In this study 296 consecutive men were treated with IMRT for adenocarcinoma of the prostate. Most patients received treatment to the prostate with or without proximal seminal vesicles (90%), to a median dose of 76 Gy. Concurrent androgen deprivation therapy was given to 150 men (51%) for a median of 4 months. Late toxicity was defined by Common Toxicity Criteria version 3.0 as greater than 3 months after radiation therapy completion. Four groupings of DVH parameters were defined, based on the percentage of rectal or bladder tissue receiving 70 Gy (V{sub 70}), 65 Gy (V{sub 65}), and 40 Gy (V{sub 40}). These DVH groupings, as well as clinical and treatment characteristics, were correlated to maximal Grade 2+ GU and GI toxicity. Results: With a median follow-up of 41 months, the 4-year freedom from maximal Grade 2+ late toxicity was 81% and 91% for GU and GI systems, respectively, and by last follow-up, the rates of Grade 2+ GU and GI toxicity were 9% and 5%, respectively. On multivariate analysis, whole-pelvic IMRT was associated with Grade 2+ GU toxicity and age was associated with Grade 2+ GI toxicity. Freedom from Grade 2+ GI toxicity at 4 years was 100% for men with rectal V{sub 70} {<=}10%, V{sub 65} {<=}20%, and V{sub 40} {<=}40%; 92% for men with rectal V{sub 70} {<=}20%, V{sub 65} {<=}40%, and V{sub 40} {<=}80%; and 85% for men exceeding these criteria (p = 0.13). These criteria were more highly associated with GI toxicity in men aged {>=}70 years (p = 0.07). No bladder dose-volume relationships were associated with the risk of GU toxicity. Conclusions: IMRT is associated with low rates of severe GU or GI toxicity after treatment for prostate cancer. Rectal dose constraints

  18. The expanding clinical phenotype of the tRNA{sup Leu(UUR)} A{r_arrow}G mutation at np 3243 of mitochondrial DNA: Diabetic embryopathy associated with mitochondrial cytopathy

    SciTech Connect

    Feigenbaum, A.; Chitayat, D.; Robinson, B.; MacGregor, D.; Myint, T.

    1996-04-24

    We describe a family which demonstrates and expands the extreme clinical variability now known to be associated with the A{r_arrow}G transition at nucleotide position 3243 of the mitochondrial DNA. The propositus presented at birth with clinical manifestations consistent with diabetic embryopathy including anal atresia, caudal dysgenesis, and multicystic dysplastic kidneys. His co-twin was normal at birth, but at 3 months of life, presented with intractable seizures later associated with developmental delay. The twins` mother developed diabetes mellitus type I at the age of 20 years and gastrointestinal problems at 22 years. Since age 19 years, the maternal aunt has had recurrent strokes, seizures, mental deterioration and deafness, later diagnosed as MELAS syndrome due to the tRNA{sup Leu(UUR)} A{r_arrow}G mutation. A maternal uncle had diabetes mellitus type I, deafness, and normal intellect, and died at 35 years after recurrent strokes. This pedigree expands the known clinical phenotype associated with tRNA{sup Leu(UUR)} A{r_arrow}G mutation and raises the possibility that, in some cases, diabetic embryopathy may be due to a mitochondrial cytopathy that affects both the mother`s pancreas (and results in diabetes mellitus and the metabolic dysfunction associated with it) and the embryonic/fetal and placental tissues which make the embryo more vulnerable to this insult. 33 refs., 1 tab.

  19. Two New Nuclear Isolation Buffers for Plant DNA Flow Cytometry: A Test with 37 Species

    PubMed Central

    Loureiro, João; Rodriguez, Eleazar; Doležel, Jaroslav; Santos, Conceição

    2007-01-01

    Background and Aims After the initial boom in the application of flow cytometry in plant sciences in the late 1980s and early 1990s, which was accompanied by development of many nuclear isolation buffers, only a few efforts were made to develop new buffer formulas. In this work, recent data on the performance of nuclear isolation buffers are utilized in order to develop new buffers, general purpose buffer (GPB) and woody plant buffer (WPB), for plant DNA flow cytometry. Methods GPB and WPB were used to prepare samples for flow cytometric analysis of nuclear DNA content in a set of 37 plant species that included herbaceous and woody taxa with leaf tissues differing in structure and chemical composition. The following parameters of isolated nuclei were assessed: forward and side light scatter, propidium iodide fluorescence, coefficient of variation of DNA peaks, quantity of debris background, and the number of particles released from sample tissue. The nuclear genome size of 30 selected species was also estimated using the buffer that performed better for a given species. Key Results In unproblematic species, the use of both buffers resulted in high quality samples. The analysis of samples obtained with GPB usually resulted in histograms of DNA content with higher or similar resolution than those prepared with the WPB. In more recalcitrant tissues, such as those from woody plants, WPB performed better and GPB failed to provide acceptable results in some cases. Improved resolution of DNA content histograms in comparison with previously published buffers was achieved in most of the species analysed. Conclusions WPB is a reliable buffer which is also suitable for the analysis of problematic tissues/species. Although GPB failed with some plant species, it provided high-quality DNA histograms in species from which nuclear suspensions are easy to prepare. The results indicate that even with a broad range of species, either GPB or WPB is suitable for preparation of high

  20. Cloned Genomic DNA of Type 2 Porcine Circovirus Is Infectious When Injected Directly into the Liver and Lymph Nodes of Pigs: Characterization of Clinical Disease, Virus Distribution, and Pathologic Lesions

    PubMed Central

    Fenaux, M.; Halbur, P. G.; Haqshenas, G.; Royer, R.; Thomas, P.; Nawagitgul, P.; Gill, M.; Toth, T. E.; Meng, X. J.

    2002-01-01

    Infection of animals with a molecular viral clone is critical to study the genetic determinants of viral replication and virulence in the host. Type 2 porcine circovirus (PCV2) has been incriminated as the cause of postweaning multisystemic wasting syndrome (PMWS), an emerging disease in pigs. We report here for the first time the construction and use of an infectious molecular DNA clone of PCV2 to characterize the disease and pathologic lesions associated with PCV2 infection by direct in vivo transfection of pigs with the molecular clone. The PCV2 molecular clone was generated by ligating two copies of the complete PCV2 genome in tandem into the pBluescript SK (pSK) vector and was shown to be infectious in vitro when transfected into PK-15 cells. Forty specific-pathogen-free pigs at 4 weeks of age were randomly assigned to four groups of 10 each. Group 1 pigs served as uninoculated controls. Pigs in group 2 were each inoculated intranasally with about 1.9 × 105 50% tissue culture infective doses of a homogeneous PCV2 live virus stock derived from the molecular clone. Pigs in group 3 were each injected intrahepatically with 200 μg of the cloned PCV2 plasmid DNA, and pigs in group 4 were each injected into the superficial iliac lymph nodes with 200 μg of the cloned PCV2 plasmid DNA. Animals injected with the cloned PCV2 plasmid DNA developed infection resembling that induced by intranasal inoculation with PCV2 live virus stock. Seroconversion to PCV2-specific antibody was detected in the majority of pigs from the three inoculated groups at 35 days postinoculation (DPI). Viremia, beginning at 14 DPI and lasting 2 to 4 weeks, was detected in the majority of the pigs from all three inoculated groups. There were no remarkable clinical signs of PMWS in control or any of the inoculated pigs. Gross lesions in pigs of the three inoculated groups were similar and were characterized by systemically enlarged, tan lymph nodes and lungs that failed to collapse

  1. Comparison of Analytical and Clinical Performance of HPV 9G DNA Chip, PANArray HPV Genotyping Chip, and Hybrid-Capture II Assay in Cervicovaginal Swabs

    PubMed Central

    Jung, Ho Young; Han, Hye Seung; Kim, Hyo Bin; Oh, Seo Young; Lee, Sun-Joo; Kim, Wook Youn

    2016-01-01

    Background: Human papillomavirus (HPV) infection can be detected by using several molecular methods, including Hybrid-Capture II (HC2) assay and variable HPV DNA chip tests, although each method has different sensitivities and specificities. Methods: We performed HPV 9G DNA Chip (9G) and PANArray HPV Genotyping Chip (PANArray) tests on 118 cervicovaginal swabs and compared the results with HC2, cytology, histology, and direct sequencing results. Results The overall and high-risk HPV (HR-HPV) positivity rates were 62.7% and 44.9% using 9G, and 61.0% and 30.5% using PANArray, respectively. The positivity rates for HR-HPV with these two chips were significantly lower than 55.1% when HC2 was used. The sensitivity of overall HPV positivity in detecting histologically confirmed low-grade cervical squamous intraepithelial lesions or higher was 88.7% for all three tests. The specificity was 58.5% for 9G and 61.5% for PANArray, which was significantly lower than the 72.3% for HC2. With the HR-HPV+ genotype threshold, the sensitivity decreased to 75.5% for 9G and 52.8% for PANArray, which was significantly lower than the 88.7% for HC2. Comparison of the two chips showed concordant results in 55.1% of the samples, compatible results in 16.9%, and discordant results in 28.0%, exhibiting poor agreement in detecting  certain HPV genotypes. Compared with direct sequencing, 9G yielded no discordant results, whereas PANArray yielded 31 discordant results (26.7%). Conclusions Compared with HC2, the HPV genotyping tests showed lower sensitivity in histologic correlation. When the two chips were compared, the 9G was more sensitive and accurate for detecting HR-HPV than the PANArray. PMID:26763506

  2. DNA Immunization

    PubMed Central

    Wang, Shixia; Lu, Shan

    2013-01-01

    DNA immunization was discovered in early 1990s and its use has been expanded from vaccine studies to a broader range of biomedical research, such as the generation of high quality polyclonal and monoclonal antibodies as research reagents. In this unit, three common DNA immunization methods are described: needle injection, electroporation and gene gun. In addition, several common considerations related to DNA immunization are discussed. PMID:24510291

  3. Reverse Cross Blot Hybridization Assay for Rapid Detection of PCR-Amplified DNA from Candida Species, Cryptococcus neoformans, and Saccharomyces cerevisiae in Clinical Samples

    PubMed Central

    Posteraro, Brunella; Sanguinetti, Maurizio; Masucci, Luca; Romano, Lucio; Morace, Giulia; Fadda, Giovanni

    2000-01-01

    A PCR-based assay was developed to detect and identify medically important yeasts in clinical samples. Using a previously described set of primers (G. Morace et al., J. Clin. Microbiol. 35:667–672, 1997), we amplified a fragment of the ERG11 gene for cytochrome P-450 lanosterol 14α-demethylase, a crucial enzyme in the biosynthesis of ergosterol. The PCR product was analyzed in a reverse cross blot hybridization assay with species-specific probes directed to a target region of the ERG11 gene of Candida albicans (pCal), C. guilliermondii (pGui), C. (Torulopsis) glabrata (pGla), C. kefyr (pKef), C. krusei (pKru), C. parapsilosis (pPar), C. tropicalis (pTro), the newly described species C. dubliniensis (pDub), Saccharomyces cerevisiae (pSce), and Cryptococcus neoformans (pCry). The PCR-reverse cross blot hybridization assay correctly identified multiple isolates of each species tested. No cross-hybridization was detected with any other fungal, bacteria, or human DNAs tested. The method was tested against conventional identification on 140 different clinical samples, including blood and cerebrospinal fluid, from patients with suspected fungal infections. The results agreed with those of culture and phenotyping for all but six specimens (two of which grew yeasts not included in the PCR panel of probes and four in which PCR positivity-culture negativity was justified by clinical findings). Species identification time was reduced from a mean of 4 days with conventional identification to 7 h with the molecular method. The PCR-reverse cross blot hybridization assay is a rapid method for the direct detection and identification of yeasts in clinical samples. PMID:10747151

  4. Osteoarthritis Classification Using Self Organizing Map Based on Gabor Kernel and Contrast-Limited Adaptive Histogram Equalization

    PubMed Central

    Anifah, Lilik; Purnama, I Ketut Eddy; Hariadi, Mochamad; Purnomo, Mauridhi Hery

    2013-01-01

    Localization is the first step in osteoarthritis (OA) classification. Manual classification, however, is time-consuming, tedious, and expensive. The proposed system is designed as decision support system for medical doctors to classify the severity of knee OA. A method has been proposed here to localize a joint space area for OA and then classify it in 4 steps to classify OA into KL-Grade 0, KL-Grade 1, KL-Grade 2, KL-Grade 3 and KL-Grade 4, which are preprocessing, segmentation, feature extraction, and classification. In this proposed system, right and left knee detection was performed by employing the Contrast-Limited Adaptive Histogram Equalization (CLAHE) and the template matching. The Gabor kernel, row sum graph and moment methods were used to localize the junction space area of knee. CLAHE is used for preprocessing step, i.e.to normalize the varied intensities. The segmentation process was conducted using the Gabor kernel, template matching, row sum graph and gray level center of mass method. Here GLCM (contrast, correlation, energy, and homogeinity) features were employed as training data. Overall, 50 data were evaluated for training and 258 data for testing. Experimental results showed the best performance by using gabor kernel with parameters α=8, θ=0, Ψ=[0 π/2], γ=0,8, N=4 and with number of iterations being 5000, momentum value 0.5 and α0=0.6 for the classification process. The run gave classification accuracy rate of 93.8% for KL-Grade 0, 70% for KL-Grade 1, 4% for KL-Grade 2, 10% for KL-Grade 3 and 88.9% for KL-Grade 4. PMID:23525188

  5. Risk factors for neovascular glaucoma after carbon ion radiotherapy of choroidal melanoma using dose-volume histogram analysis

    SciTech Connect

    Hirasawa, Naoki . E-mail: naoki_h@nirs.go.jp; Tsuji, Hiroshi; Ishikawa, Hitoshi; Koyama-Ito, Hiroko; Kamada, Tadashi; Mizoe, Jun-Etsu; Ito, Yoshiyuki; Naganawa, Shinji; Ohnishi, Yoshitaka; Tsujii, Hirohiko

    2007-02-01

    Purpose: To determine the risk factors for neovascular glaucoma (NVG) after carbon ion radiotherapy (C-ion RT) of choroidal melanoma. Methods and Materials: A total of 55 patients with choroidal melanoma were treated between 2001 and 2005 with C-ion RT based on computed tomography treatment planning. All patients had a tumor of large size or one located close to the optic disk. Univariate and multivariate analyses were performed to identify the risk factors of NVG for the following parameters; gender, age, dose-volumes of the iris-ciliary body and the wall of eyeball, and irradiation of the optic disk (ODI). Results: Neovascular glaucoma occurred in 23 patients and the 3-year cumulative NVG rate was 42.6 {+-} 6.8% (standard error), but enucleation from NVG was performed in only three eyes. Multivariate analysis revealed that the significant risk factors for NVG were V50{sub IC} (volume irradiated {>=}50 GyE to iris-ciliary body) (p = 0.002) and ODI (p = 0.036). The 3-year NVG rate for patients with V50{sub IC} {>=}0.127 mL and those with V50{sub IC} <0.127 mL were 71.4 {+-} 8.5% and 11.5 {+-} 6.3%, respectively. The corresponding rate for the patients with and without ODI were 62.9 {+-} 10.4% and 28.4 {+-} 8.0%, respectively. Conclusion: Dose-volume histogram analysis with computed tomography indicated that V50{sub IC} and ODI were independent risk factors for NVG. An irradiation system that can reduce the dose to both the anterior segment and the optic disk might be worth adopting to investigate whether or not incidence of NVG can be decreased with it.

  6. A hybrid phase-space and histogram source model for GPU-based Monte Carlo radiotherapy dose calculation

    NASA Astrophysics Data System (ADS)

    Townson, Reid W.; Zavgorodni, Sergei

    2014-12-01

    In GPU-based Monte Carlo simulations for radiotherapy dose calculation, source modelling from a phase-space source can be an efficiency bottleneck. Previously, this has been addressed using phase-space-let (PSL) sources, which provided significant efficiency enhancement. We propose that additional speed-up can be achieved through the use of a hybrid primary photon point source model combined with a secondary PSL source. A novel phase-space derived and histogram-based implementation of this model has been integrated into gDPM v3.0. Additionally, a simple method for approximately deriving target photon source characteristics from a phase-space that does not contain inheritable particle history variables (LATCH) has been demonstrated to succeed in selecting over 99% of the true target photons with only ~0.3% contamination (for a Varian 21EX 18 MV machine). The hybrid source model was tested using an array of open fields for various Varian 21EX and TrueBeam energies, and all cases achieved greater than 97% chi-test agreement (the mean was 99%) above the 2% isodose with 1% / 1 mm criteria. The root mean square deviations (RMSDs) were less than 1%, with a mean of 0.5%, and the source generation time was 4-5 times faster. A seven-field intensity modulated radiation therapy patient treatment achieved 95% chi-test agreement above the 10% isodose with 1% / 1 mm criteria, 99.8% for 2% / 2 mm, a RMSD of 0.8%, and source generation speed-up factor of 2.5. Presented as part of the International Workshop on Monte Carlo Techniques in Medical Physics

  7. Outcomes of visual acuity in carbon ion radiotherapy: Analysis of dose-volume histograms and prognostic factors

    SciTech Connect

    Hasegawa, Azusa . E-mail: azusa@nirs.go.jp; Mizoe, Jun-etsu; Mizota, Atsushi; Tsujii, Hirohiko

    2006-02-01

    Purpose: To analyze the tolerance dose for retention of visual acuity in patients with head-and-neck tumors treated with carbon ion radiotherapy. Methods and Materials: From June 1994 to March 2000, 163 patients with tumors in the head and neck or skull base region were treated with carbon ion radiotherapy. Analysis was performed on 54 optic nerves (ONs) corresponding to 30 patients whose ONs had been included in the irradiated volume. These patients showed no evidence of visual impairment due to other factors and had a follow-up period of >4 years. All patients had been informed of the possibility of visual impairment before treatment. We evaluated the dose-complication probability and the prognostic factors for the retention of visual acuity in carbon ion radiotherapy, using dose-volume histograms and multivariate analysis. Results: The median age of 30 patients (14 men, 16 women) was 57.2 years. Median prescribed total dose was 56.0 gray equivalents (GyE) at 3.0-4.0 GyE per fraction per day (range, 48-64 GyE; 16-18 fractions; 4-6 weeks). Of 54 ONs that were analyzed, 35 had been irradiated with <57 GyE (maximum dose [D{sub max}]) resulting in no visual loss. Conversely, 11 of the 19 ONs (58%) irradiated with >57 GyE (D{sub max}) suffered a decrease of visual acuity. In all of these cases, the ONs had been involved in the tumor before carbon ion radiotherapy. In the multivariate analysis, a dose of 20% of the volume of the ON (D{sub 2}) was significantly associated with visual loss. Conclusions: The occurrence of visual loss seems to be correlated with a delivery of >60 GyE to 20% of the volume of the ON.

  8. Quantifying the Impact of Immediate Reconstruction in Postmastectomy Radiation: A Large, Dose-Volume Histogram-Based Analysis

    SciTech Connect

    Ohri, Nisha; Cordeiro, Peter G.; Keam, Jennifer; Ballangrud, Ase; Shi Weiji; Zhang Zhigang; Nerbun, Claire T.; Woch, Katherine M.; Stein, Nicholas F.; Zhou Ying; McCormick, Beryl; Powell, Simon N.; Ho, Alice Y.

    2012-10-01

    Purpose: To assess the impact of immediate breast reconstruction on postmastectomy radiation (PMRT) using dose-volume histogram (DVH) data. Methods and Materials: Two hundred forty-seven women underwent PMRT at our center, 196 with implant reconstruction and 51 without reconstruction. Patients with reconstruction were treated with tangential photons, and patients without reconstruction were treated with en-face electron fields and customized bolus. Twenty percent of patients received internal mammary node (IMN) treatment. The DVH data were compared between groups. Ipsilateral lung parameters included V20 (% volume receiving 20 Gy), V40 (% volume receiving 40 Gy), mean dose, and maximum dose. Heart parameters included V25 (% volume receiving 25 Gy), mean dose, and maximum dose. IMN coverage was assessed when applicable. Chest wall coverage was assessed in patients with reconstruction. Propensity-matched analysis adjusted for potential confounders of laterality and IMN treatment. Results: Reconstruction was associated with lower lung V20, mean dose, and maximum dose compared with no reconstruction (all P<.0001). These associations persisted on propensity-matched analysis (all P<.0001). Heart doses were similar between groups (P=NS). Ninety percent of patients with reconstruction had excellent chest wall coverage (D95 >98%). IMN coverage was superior in patients with reconstruction (D95 >92.0 vs 75.7%, P<.001). IMN treatment significantly increased lung and heart parameters in patients with reconstruction (all P<.05) but minimally affected those without reconstruction (all P>.05). Among IMN-treated patients, only lower lung V20 in those without reconstruction persisted (P=.022), and mean and maximum heart doses were higher than in patients without reconstruction (P=.006, P=.015, respectively). Conclusions: Implant reconstruction does not compromise the technical quality of PMRT when the IMNs are untreated. Treatment technique, not reconstruction, is the primary

  9. Osteoarthritis classification using self organizing map based on gabor kernel and contrast-limited adaptive histogram equalization.

    PubMed

    Anifah, Lilik; Purnama, I Ketut Eddy; Hariadi, Mochamad; Purnomo, Mauridhi Hery

    2013-01-01

    Localization is the first step in osteoarthritis (OA) classification. Manual classification, however, is time-consuming, tedious, and expensive. The proposed system is designed as decision support system for medical doctors to classify the severity of knee OA. A method has been proposed here to localize a joint space area for OA and then classify it in 4 steps to classify OA into KL-Grade 0, KL-Grade 1, KL-Grade 2, KL-Grade 3 and KL-Grade 4, which are preprocessing, segmentation, feature extraction, and classification. In this proposed system, right and