Science.gov

Sample records for multiple markers analyzed

  1. Multiple capillary biochemical analyzer

    DOEpatents

    Dovichi, N.J.; Zhang, J.Z.

    1995-08-08

    A multiple capillary analyzer allows detection of light from multiple capillaries with a reduced number of interfaces through which light must pass in detecting light emitted from a sample being analyzed, using a modified sheath flow cuvette. A linear or rectangular array of capillaries is introduced into a rectangular flow chamber. Sheath fluid draws individual sample streams through the cuvette. The capillaries are closely and evenly spaced and held by a transparent retainer in a fixed position in relation to an optical detection system. Collimated sample excitation radiation is applied simultaneously across the ends of the capillaries in the retainer. Light emitted from the excited sample is detected by the optical detection system. The retainer is provided by a transparent chamber having inward slanting end walls. The capillaries are wedged into the chamber. One sideways dimension of the chamber is equal to the diameter of the capillaries and one end to end dimension varies from, at the top of the chamber, slightly greater than the sum of the diameters of the capillaries to, at the bottom of the chamber, slightly smaller than the sum of the diameters of the capillaries. The optical system utilizes optic fibers to deliver light to individual photodetectors, one for each capillary tube. A filter or wavelength division demultiplexer may be used for isolating fluorescence at particular bands. 21 figs.

  2. Multiple capillary biochemical analyzer

    DOEpatents

    Dovichi, Norman J.; Zhang, Jian Z.

    1995-01-01

    A multiple capillary analyzer allows detection of light from multiple capillaries with a reduced number of interfaces through which light must pass in detecting light emitted from a sample being analyzed, using a modified sheath flow cuvette. A linear or rectangular array of capillaries is introduced into a rectangular flow chamber. Sheath fluid draws individual sample streams through the cuvette. The capillaries are closely and evenly spaced and held by a transparent retainer in a fixed position in relation to an optical detection system. Collimated sample excitation radiation is applied simultaneously across the ends of the capillaries in the retainer. Light emitted from the excited sample is detected by the optical detection system. The retainer is provided by a transparent chamber having inward slanting end walls. The capillaries are wedged into the chamber. One sideways dimension of the chamber is equal to the diameter of the capillaries and one end to end dimension varies from, at the top of the chamber, slightly greater than the sum of the diameters of the capillaries to, at the bottom of the chamber, slightly smaller than the sum of the diameters of the capillaries. The optical system utilizes optic fibres to deliver light to individual photodetectors, one for each capillary tube. A filter or wavelength division demultiplexer may be used for isolating fluorescence at particular bands.

  3. Multiple capillary biochemical analyzer with barrier member

    DOEpatents

    Dovichi, N.J.; Zhang, J.Z.

    1996-10-22

    A multiple capillary biochemical analyzer is disclosed for sequencing DNA and performing other analyses, in which a set of capillaries extends from wells in a microtiter plate into a cuvette. In the cuvette the capillaries are held on fixed closely spaced centers by passing through a sandwich construction having a pair of metal shims which squeeze between them a rubber gasket, forming a leak proof seal for an interior chamber in which the capillary ends are positioned. Sheath fluid enters the chamber and entrains filament sample streams from the capillaries. The filament sample streams, and sheath fluid, flow through aligned holes in a barrier member spaced close to the capillary ends, into a collection chamber having a lower glass window. The filament streams are illuminated above the barrier member by a laser, causing them to fluoresce. The fluorescence is viewed end-on by a CCD camera chip located below the glass window. The arrangement ensures an equal optical path length from all fluorescing spots to the CCD chip and also blocks scattered fluorescence illumination, providing more uniform results and an improved signal-to-noise ratio. 12 figs.

  4. Multiple capillary biochemical analyzer with barrier member

    DOEpatents

    Dovichi, Norman J.; Zhang, Jian Z.

    1996-01-01

    A multiple capillary biochemical analyzer for sequencing DNA and performing other analyses, in which a set of capillaries extends from wells in a microtiter plate into a cuvette. In the cuvette the capillaries are held on fixed closely spaced centers by passing through a sandwich construction having a pair of metal shims which squeeze between them a rubber gasket, forming a leak proof seal for an interior chamber in which the capillary ends are positioned. Sheath fluid enters the chamber and entrains filament sample streams from the capillaries. The filament sample streams, and sheath fluid, flow through aligned holes in a barrier member spaced close to the capillary ends, into a collection chamber having a lower glass window. The filament streams are illuminated above the barrier member by a laser, causing them to fluoresce. The fluorescence is viewed end-on by a CCD camera chip located below the glass window. The arrangement ensures an equal optical path length from all fluorescing spots to the CCD chip and also blocks scattered fluorescence illumination, providing more uniform results and an improved signal to noise ratio.

  5. Tracking of multiple points using color video image analyzer

    NASA Astrophysics Data System (ADS)

    Nennerfelt, Leif

    1990-08-01

    The Videomex-X is a new product intended for use in biomechanical measurement. It tracks up to six points at 60 frames per second using colored markers placed on the subject. The system can be used for applications such as gait analysis, studying facial movements, or tracking the pattern of movements of individuals in a group. The Videomex-X is comprised of a high speed color image analyzer, an RBG color video camera, an IBM AT compatible computer and motion analysis software. The markers are made from brightly colored plastic disks and each marker is a different color. Since the markers are unique, the problem of misidentification of markers does not occur. The Videomex-X performs realtime analysis so that the researcher can get immediate feedback on the subject's performance. High speed operation is possible because the system uses distributed processing. The image analyzer is a hardwired parallel image processor which identifies the markers within the video picture and computes their x-y locations. The image analyzer sends the x-y coordinates to the AT computer which performs additional analysis and presents the result. The x-y coordinate data acquired during the experiment may be streamed to the computer's hard disk. This allows the data to be re-analyzed repeatedly using different analysis criteria. The original Videomex-X tracked in two dimensions. However, a 3-D system has recently been completed. The algorithm used by the system to derive performance results from the x-y coordinates is contained in a separate ASCII file. These files can be modified by the operator to produce the required type of data reduction.

  6. Analyzing Student Confidence in Classroom Voting with Multiple Choice Questions

    ERIC Educational Resources Information Center

    Stewart, Ann; Storm, Christopher; VonEpps, Lahna

    2013-01-01

    The purpose of this paper is to present results of a recent study in which students voted on multiple choice questions in mathematics courses of varying levels. Students used clickers to select the best answer among the choices given; in addition, they were also asked whether they were confident in their answer. In this paper we analyze data…

  7. Analyzing Student Confidence in Classroom Voting with Multiple Choice Questions

    ERIC Educational Resources Information Center

    Stewart, Ann; Storm, Christopher; VonEpps, Lahna

    2013-01-01

    The purpose of this paper is to present results of a recent study in which students voted on multiple choice questions in mathematics courses of varying levels. Students used clickers to select the best answer among the choices given; in addition, they were also asked whether they were confident in their answer. In this paper we analyze data…

  8. Fluoroscopic tracking of multiple implanted fiducial markers using multiple object tracking.

    PubMed

    Tang, Xiaoli; Sharp, Greg C; Jiang, Steve B

    2007-07-21

    When treating mobile tumors using techniques such as beam gating or beam tracking, precise localization of tumor position is required, which is often realized by fluoroscopically tracking implanted fiducial markers. Multiple markers placed inside or near a tumor are often preferred to a single marker for the sake of accuracy. In this work, we propose a marker tracking system that can track multiple markers simultaneously, without confusing them, and that is also robust enough to continue tracking even when the markers are moving behind bony anatomy. The integrated radiotherapy imaging system (IRIS), developed at the Massachusetts General Hospital (MGH), was used to take fluoroscopy videos for marker tracking. The tracking system integrates marker detection with a multiple object tracking process, inspired by the multiple hypothesis marker tracking (MHT) process. It also utilizes breathing pattern information to help tracking. Four criteria are used to identify tracking failure, and when tracking failure occurs, the system can immediately inform the user. (In the clinical environment, the system would immediately disable the treatment beam.) In this paper, two liver patients with implanted fiducial markers were studied, and the studies were performed retrospectively to assess the effectiveness of the new tracking system. For both patients, LAT and AP fluoroscopic videos were studied. In order to better test the proposed tracking system, artificial markers were added around the real markers to disturb the tracking of the real markers. The performance of the proposed system was compared to that of a conventional tracking system (one that did not use multiple object tracking). The performance of the new system was also investigated with and without consideration of the breathing pattern information. We found that the conventional tracking system can easily miss tracking markers in the presence of artificial markers, and it cannot detect the tracking failures. On the

  9. Fluoroscopic tracking of multiple implanted fiducial markers using multiple object tracking

    NASA Astrophysics Data System (ADS)

    Tang, Xiaoli; Sharp, Greg C.; Jiang, Steve B.

    2007-07-01

    When treating mobile tumors using techniques such as beam gating or beam tracking, precise localization of tumor position is required, which is often realized by fluoroscopically tracking implanted fiducial markers. Multiple markers placed inside or near a tumor are often preferred to a single marker for the sake of accuracy. In this work, we propose a marker tracking system that can track multiple markers simultaneously, without confusing them, and that is also robust enough to continue tracking even when the markers are moving behind bony anatomy. The integrated radiotherapy imaging system (IRIS), developed at the Massachusetts General Hospital (MGH), was used to take fluoroscopy videos for marker tracking. The tracking system integrates marker detection with a multiple object tracking process, inspired by the multiple hypothesis marker tracking (MHT) process. It also utilizes breathing pattern information to help tracking. Four criteria are used to identify tracking failure, and when tracking failure occurs, the system can immediately inform the user. (In the clinical environment, the system would immediately disable the treatment beam.) In this paper, two liver patients with implanted fiducial markers were studied, and the studies were performed retrospectively to assess the effectiveness of the new tracking system. For both patients, LAT and AP fluoroscopic videos were studied. In order to better test the proposed tracking system, artificial markers were added around the real markers to disturb the tracking of the real markers. The performance of the proposed system was compared to that of a conventional tracking system (one that did not use multiple object tracking). The performance of the new system was also investigated with and without consideration of the breathing pattern information. We found that the conventional tracking system can easily miss tracking markers in the presence of artificial markers, and it cannot detect the tracking failures. On the

  10. A strategy for using multiple linked markers for genetic counseling.

    PubMed Central

    Chakravarti, A; Buetow, K H

    1985-01-01

    A strategy for using multiple linked markers for genetic counseling is to test sequentially individual markers until a diagnosis can be made. We show that in order to minimize the number of tests performed per case while diagnosing all informative cases the order in which the markers are to be tested is critical. We describe an algorithm to obtain this order using the parameter "I," the frequency of informative cases. The I value for a specific locus used depends on the marker frequency, association with the disease locus, and also on the informativeness of the marker loci already tested. Realizing that a direct assay for the beta S gene already exists, and that most cases of beta-thalassemia in Mediterraneans can be directly diagnosed using synthetic oligonucleotide probes, we illustrate the above technique by examining nine DNA polymorphisms in the human beta-globin cluster for their ability to diagnose sickle-cell anemia in American blacks and beta-thalassemia in Mediterraneans. This analysis shows that 95.39% of all sickle-cell pregnancies can be diagnosed by testing a subset of only six markers chosen by our algorithm. Furthermore, six markers can also diagnose 88.03% of beta-thalassemia in Greeks and 83.56% of beta-thalassemia in Italians. The test set is different from that suggested by the individual informative frequencies due to nonrandom associations between the restriction sites. PMID:2996337

  11. Using Live-Cell Markers in Maize to Analyze Cell Division Orientation and Timing.

    PubMed

    Rasmussen, Carolyn G

    2016-01-01

    Recently developed live-cell markers provide an opportunity to explore the dynamics and localization of proteins in maize, an important crop and model for monocot development. A step-by-step method is outlined for observing and analyzing the process of division in maize cells. The steps include plant growth conditions, sample preparation, time-lapse setup, and calculation of division rates.

  12. A traffic analyzer for multiple SpaceWire links

    NASA Astrophysics Data System (ADS)

    Liu, Scige J.; Giusi, Giovanni; Di Giorgio, Anna M.; Vertolli, Nello; Galli, Emanuele; Biondi, David; Farina, Maria; Pezzuto, Stefano; Spinoglio, Luigi

    2014-07-01

    Modern space missions are becoming increasingly complex: the interconnection of the units in a satellite is now a network of terminals linked together through routers, where devices with different level of automation and intelligence share the same data-network. The traceability of the network transactions is performed mostly at terminal level through log analysis and hence it is difficult to verify in real time the reliability of the interconnections and the interchange protocols. To improve and ease the traffic analysis in a SpaceWire network we implemented a low-level link analyzer, with the specific goal to simplify the integration and test phases in the development of space instrumentation. The traffic analyzer collects signals coming from pod probes connected in-series on the interested links between two SpaceWire terminals. With respect to the standard traffic analyzers, the design of this new tool includes the possibility to internally reshape the LVDS signal. This improvement increases the robustness of the analyzer towards environmental noise effects and guarantees a deterministic delay on all analyzed signals. The analyzer core is implemented on a Xilinx FPGA, programmed to decode the bidirectional LVDS signals at Link and Network level. Successively, the core packetizes protocol characters in homogeneous sets of time ordered events. The analyzer provides time-tagging functionality for each characters set, with a precision down to the FPGA Clock, i.e. about 20nsec in the adopted HW environment. The use of a common time reference for each character stream allows synchronous performance measurements. The collected information is then routed to an external computer for quick analysis: this is done via high-speed USB2 connection. With this analyzer it is possible to verify the link performances in terms of induced delays in the transmitted signals. A case study focused on the analysis of the Time-Code synchronization in presence of a SpaceWire Router is

  13. The correlation evaluation of a tumor tracking system using multiple external markers

    SciTech Connect

    Yan Hui; Yin Fangfang; Zhu Guopei; Ajlouni, Munther; Kim, Jae Ho

    2006-11-15

    The purpose of this study is to evaluate the correlations between external markers and internal targets for radiation therapy of lung cancer patients. Using an infrared camera system coupled with a clinical simulator, the simultaneous motions of multiple external markers and an internal target were obtained. The correlation between external and internal signals was analyzed using a cross-covariance function. A linear regression model was employed to generate a composite signal from multiple external markers in order to predict the internal target motion. The external and internal signals, and their correlations, demonstrated a wide range of variation with respect to marker location, motion dimension, and breathing pattern. The performance of the composite signal indicates that when more external signals were taken into account, the mean correlation between the composite signal and internal signal was improved. This implies that a combination of multiple external signals might be an improved way to predict internal target motion. Also, since the characteristics of respiratory signals can vary significantly, certain methods of preprocessing and external signal combination are necessary.

  14. The correlation evaluation of a tumor tracking system using multiple external markers.

    PubMed

    Yan, Hui; Yin, Fang-Fang; Zhu, Guo-Pei; Ajlouni, Munther; Kim, Jae Ho

    2006-11-01

    The purpose of this study is to evaluate the correlations between external markers and internal targets for radiation therapy of lung cancer patients. Using an infrared camera system coupled with a clinical simulator, the simultaneous motions of multiple external markers and an internal target were obtained. The correlation between external and internal signals was analyzed using a cross-covariance function. A linear regression model was employed to generate a composite signal from multiple external markers in order to predict the internal target motion. The external and internal signals, and their correlations, demonstrated a wide range of variation with respect to marker location, motion dimension, and breathing pattern. The performance of the composite signal indicates that when more external signals were taken into account, the mean correlation between the composite signal and internal signal was improved. This implies that a combination of multiple external signals might be an improved way to predict internal target motion. Also, since the characteristics of respiratory signals can vary significantly, certain methods of preprocessing and external signal combination are necessary.

  15. Genetic diversity of Mycosphaerella fijiensis in Brazil analyzed using an ERIC-PCR marker.

    PubMed

    Silva, G F; Paixão, R D V; Queiroz, C B; Santana, M F; Souza, A; Sousa, N R; Hanada, R E; Gasparotto, L

    2014-09-26

    The Enterobacterial repetitive intergenic consensus (ERIC) marker was used to analyze the genetic variability of Mycosphaerella fijiensis, the causative agent of Black Sigatoka disease in banana plants. A total of 123 isolates were used, which were divided into populations based on their original hosts and collection sites in Brazil. A total of 9 loci were amplified, 77.8% of which were found to be polymorphic. The genetic diversity found in the population was 0.20. Analysis of molecular variance (AMOVA) demonstrated that the highest level of genetic variation is within populations. Cluster analysis revealed three main groups in Brazil, with no correlation between geographic and genetic distance.

  16. Analyzing multiple nonlinear time series with extended Granger causality

    NASA Astrophysics Data System (ADS)

    Chen, Yonghong; Rangarajan, Govindan; Feng, Jianfeng; Ding, Mingzhou

    2004-04-01

    Identifying causal relations among simultaneously acquired signals is an important problem in multivariate time series analysis. For linear stochastic systems Granger proposed a simple procedure called the Granger causality to detect such relations. In this work we consider nonlinear extensions of Granger's idea and refer to the result as extended Granger causality. A simple approach implementing the extended Granger causality is presented and applied to multiple chaotic time series and other types of nonlinear signals. In addition, for situations with three or more time series we propose a conditional extended Granger causality measure that enables us to determine whether the causal relation between two signals is direct or mediated by another process.

  17. Analyzing Multiple Outcomes in Clinical Research Using Multivariate Multilevel Models

    PubMed Central

    Baldwin, Scott A.; Imel, Zac E.; Braithwaite, Scott R.; Atkins, David C.

    2014-01-01

    Objective Multilevel models have become a standard data analysis approach in intervention research. Although the vast majority of intervention studies involve multiple outcome measures, few studies use multivariate analysis methods. The authors discuss multivariate extensions to the multilevel model that can be used by psychotherapy researchers. Method and Results Using simulated longitudinal treatment data, the authors show how multivariate models extend common univariate growth models and how the multivariate model can be used to examine multivariate hypotheses involving fixed effects (e.g., does the size of the treatment effect differ across outcomes?) and random effects (e.g., is change in one outcome related to change in the other?). An online supplemental appendix provides annotated computer code and simulated example data for implementing a multivariate model. Conclusions Multivariate multilevel models are flexible, powerful models that can enhance clinical research. PMID:24491071

  18. Analyzing multiple spike trains with nonparametric Granger causality.

    PubMed

    Nedungadi, Aatira G; Rangarajan, Govindan; Jain, Neeraj; Ding, Mingzhou

    2009-08-01

    Simultaneous recordings of spike trains from multiple single neurons are becoming commonplace. Understanding the interaction patterns among these spike trains remains a key research area. A question of interest is the evaluation of information flow between neurons through the analysis of whether one spike train exerts causal influence on another. For continuous-valued time series data, Granger causality has proven an effective method for this purpose. However, the basis for Granger causality estimation is autoregressive data modeling, which is not directly applicable to spike trains. Various filtering options distort the properties of spike trains as point processes. Here we propose a new nonparametric approach to estimate Granger causality directly from the Fourier transforms of spike train data. We validate the method on synthetic spike trains generated by model networks of neurons with known connectivity patterns and then apply it to neurons simultaneously recorded from the thalamus and the primary somatosensory cortex of a squirrel monkey undergoing tactile stimulation.

  19. Surface markers on lymphocytes of multiple sclerosis patients.

    PubMed Central

    Nowak, J; Wajgt, A

    1975-01-01

    Peripheral blood lymphocytes of twenty-two multiple sclerosis (MS) patients and thirty-five healthy controls were examined for the presence of surface markers characteristic for B lymphocytes (surface immunoglobulin, receptor for C3 (EAC), reporter for Fc (EA) and the spontaneous rosette-forming capacity characteristic of T cells. The results obtained indicate that the number of B and T cells in MS is similar to controls, as evaluated by the presence of surface immunoglobulin and E rosette-forming capacity. However, a statistically significant reduction in the percentage of lymphocytes bearing C3 receptors has been found in MS patients. It might have resulted from a reduction in the lymphocyte population bearing C3 receptor but no surface immunoglobulin. The EA rosette test revealed the greatest difference between the groups. The difference indicated a reduction in the density of the receptor for 7S Fc on lymphocytes from MS patients. The results obtained are consistent with the hypothesis of an immune deficit in multiple sclerosis. PMID:1102165

  20. Development of a Multiple-Stage Differential Mobility Analyzer (MDMA)

    SciTech Connect

    Chen, Da-Ren; Cheng, Mengdawn

    2007-01-01

    A new DMA column has been designed with the capability of simultaneously extracting monodisperse particles of different sizes in multiple stages. We call this design a multistage DMA, or MDMA. A prototype MDMA has been constructed and experimentally evaluated in this study. The new column enables the fast measurement of particles in a wide size range, while preserving the powerful particle classification function of a DMA. The prototype MDMA has three sampling stages, capable of classifying monodisperse particles of three different sizes simultaneously. The scanning voltage operation of a DMA can be applied to this new column. Each stage of MDMA column covers a fraction of the entire particle size range to be measured. The covered size fractions of two adjacent stages of the MDMA are designed somewhat overlapped. The arrangement leads to the reduction of scanning voltage range and thus the cycling time of the measurement. The modular sampling stage design of the MDMA allows the flexible configuration of desired particle classification lengths and variable number of stages in the MDMA. The design of our MDMA also permits operation at high sheath flow, enabling high-resolution particle size measurement and/or reduction of the lower sizing limit. Using the tandem DMA technique, the performance of the MDMA, i.e., sizing accuracy, resolution, and transmission efficiency, was evaluated at different ratios of aerosol and sheath flowrates. Two aerosol sampling schemes were investigated. One was to extract aerosol flows at an evenly partitioned flowrate at each stage, and the other was to extract aerosol at a rate the same as the polydisperse aerosol flowrate at each stage. We detail the prototype design of the MDMA and the evaluation result on the transfer functions of the MDMA at different particle sizes and operational conditions.

  1. Cerebrospinal fluid markers reveal intrathecal inflammation in progressive multiple sclerosis.

    PubMed

    Komori, Mika; Blake, Andrew; Greenwood, Mark; Lin, Yen Chih; Kosa, Peter; Ghazali, Danish; Winokur, Paige; Natrajan, Muktha; Wuest, Simone C; Romm, Elena; Panackal, Anil A; Williamson, Peter R; Wu, Tianxia; Bielekova, Bibiana

    2015-07-01

    The management of complex patients with neuroimmunological diseases is hindered by an inability to reliably measure intrathecal inflammation. Currently implemented laboratory tests developed >40 years ago either are not dynamic or fail to capture low levels of central nervous system (CNS) inflammation. Therefore, we aimed to identify and validate biomarkers of CNS inflammation in 2 blinded, prospectively acquired cohorts of untreated patients with neuroimmunological diseases and embedded controls, with the ultimate goal of developing clinically useful tools. Because biomarkers with maximum utility reflect immune phenotypes, we included an assessment of cell specificity in purified primary immune cells. Biomarkers were quantified by optimized electrochemiluminescent immunoassays. Among markers with cell-specific secretion, soluble CD27 is a validated biomarker of intrathecal T-cell activation, with an area under the receiver operating characteristic curve of 0.97. Comparing the quantities of cerebrospinal fluid (CSF) immune cells and their respective cell-specific soluble biomarkers (released by CSF cells as well as their counterparts in CNS tissue) provided invaluable information about stationary CNS immune responses, previously attainable via brain biopsy only. Unexpectedly, progressive and relapsing-remitting multiple sclerosis (MS) patients have comparable numbers of activated intrathecal T and B cells, which are preferentially embedded in CNS tissue in the former group. The cell-specific biomarkers of intrathecal inflammation may improve diagnosis and management of neuroimmunological diseases and provide pharmacodynamic markers for future therapeutic developments in patients with intrathecal inflammation that is not captured by imaging, such as in progressive MS. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

  2. HLA-class I markers and multiple sclerosis susceptibility in the Italian population

    PubMed Central

    Bergamaschi, L; Leone, M A; Fasano, M E; Guerini, F R; Ferrante, D; Bolognesi, E; Barizzone, N; Corrado, L; Naldi, P; Agliardi, C; Dametto, E; Salvetti, M; Visconti, A; Galimberti, D; Scarpini, E; Vercellino, M; Bergamaschi, R; Monaco, F; Caputo, D; Momigliano-Richiardi, P; D'Alfonso, S

    2009-01-01

    Previous studies reported an association with multiple sclerosis (MS) of distinct HLA-class I markers, namely HLA-A*02, HLA-Cw*05 and MOG-142L. In this work, we tested the association with MS of A*02 and Cw*05 in 1273 Italian MS patients and 1075 matched controls, which were previously analyzed for MOG-142, and explored the relationship among these three markers in modulating MS risk. HLA-A*02 conferred a statistically robust MS protection (odds ratio, OR=0.61; 95% confidence intervals, CI=0.51–0.72, P<10−9), which was independent of DRB1*15 and of any other DRB1* allele and remained similar after accounting for the other two analyzed class I markers. Conversely, the protective effect we previously observed for MOG-142L was secondary to its linkage disequilibrium with A*02. Cw*05 was not associated considering the whole sample, but its presence significantly enhanced the protection in the HLA-A*02-positive group, independently of DRB1: the OR conferred by A*02 in Cw*05-positive individuals (0.22, 95% CI=0.13–0.38) was significantly lower than in Cw*05-negative individuals (0.69, 95% CI=0.58–0.83) with a significant (P=4.94 × 10−5) multiplicative interaction between the two markers. In the absence of A*02, Cw*05 behaved as a risk factor, particularly in combination with DRB1*03 (OR=3.89, P=0.0006), indicating that Cw*05 might be a marker of protective or risk haplotypes, respectively. PMID:19907433

  3. Analyzing the multiple-target-multiple-agent scenario using optimal assignment algorithms

    SciTech Connect

    Kwok, K.S.; Driessen, B.J.; Phillips, C.A.; Tovey, C.A.

    1997-10-01

    This work considers the problem of maximum utilization of a set of mobile robots with limited sensor-range capabilities and limited travel distances. The robots are initially in random positions. A set of robots properly guards or covers a region if every point within the region is within the effective sensor range of at least one vehicle. The authors wish to move the vehicles into surveillance positions so as to guard or cover a region, while minimizing the maximum distance traveled by any vehicle. This problem can be formulated as an assignment problem, in which they must optimally decide which robot to assign to which slot of a desired matrix of grid points. The cost function is the maximum distance traveled by any robot. Assignment problems can be solved very efficiently. Solutions times for one hundred robots took only seconds on a Silicon Graphics Crimson workstation. The initial positions of all the robots can be sampled by a central base station and their newly assigned positions communicated back to the robots. Alternatively, the robots can establish their own coordinate system with the origin fixed at one of the robots and orientation determined by the compass bearing of another robot relative to this robot. This paper presents example solutions to the multiple-target-multiple-agent scenario using a matching algorithm. Two separate cases with one hundred agents in each were analyzed using this method. They have found these mobile robot problems to be a very interesting application of network optimization methods, and they expect this to be a fruitful area for future research.

  4. Genetic Biodiversity of Italian Olives (Olea europaea) Germplasm Analyzed by SSR Markers

    PubMed Central

    Vendramin, Giuseppe Giovanni; Chiappetta, Adriana

    2014-01-01

    The olive is an important fruit species cultivated for oil and table olives in Italy and the Mediterranean basin. The conservation of cultivated plants in ex situ collections is essential for the optimal management and use of their genetic resources. The largest ex situ olive germplasm collection consists of approximately 500 Italian olive varieties and corresponding to 85% of the total Italian olive germplasm is maintained at the Consiglio per la Ricerca e sperimentazione per l'Agricoltura, Centro di Ricerca per l'Olivicoltura e l'Industria Olearia (CRA-OLI), in Italy. In this work, eleven preselected nuclear microsatellite markers were used to assess genetic diversity, population structure, and gene flows with the aim of assembling a core collection. The dendrogram obtained utilizing the unweighted pair group method highlights the presence of homonymy and synonymy in olive tree datasets analyzed in this study. 439 different unique genotype profiles were obtained with this combination of 11 loci nSSR, representing 89.8% of the varieties analyzed. The remaining 10.2% comprises different variety pairs in which both accessions are genetically indistinguishable. Clustering analysis performed using BAPS software detected seven groups in Italian olive germplasm and gene flows were determined among identified clusters. We proposed an Italian core collection of 23 olive varieties capturing all detected alleles at microsatellites. The information collected in this study regarding the CRA-OLI ex situ collection can be used for breeding programs, for germplasm conservation, and for optimizing a strategy for the management of olive gene pools. PMID:24723801

  5. [Cloning and analyzing of the female-specific marker in the dioecious species Asparagus officinalis L].

    PubMed

    Lu, Long Dou; Li, Rui Li; Gao, Wu Jun; Deng, Chuan Liang; Wang, Lian Jun

    2006-06-01

    Sex-linked molecular markers are being obtained, which would be essential to be used in the screening of different sex of dioecious plants at the seedling stage. Furthermore, it is important in cloning the gene related to the sex. In this study the random amplified polymorphic DNA (RAPD) technique was employed with the objective to find markers linked to sex determination in Asparagus. A total of 100 primers were tested with the same PCR cycling procedure. A female-associated fragment with a length of about 867bp was generated with S12 primer. The fragment was cloned and sequenced, showing it is abundant in AT and contains 2 shorter open reading frames. In order to convert the RAPD marker into SCAR (sequence characterized amplified regions) marker, 24bp specific primers were constructed and used for PCR amplifying. The female-linked dominant SCAR marker was obtained, which would be efficient to identify the different sex of Asparagus officinalis L.

  6. Multiple Brain Markers are Linked to Age-Related Variation in Cognition

    PubMed Central

    Hedden, Trey; Schultz, Aaron P.; Rieckmann, Anna; Mormino, Elizabeth C.; Johnson, Keith A.; Sperling, Reisa A.; Buckner, Randy L.

    2016-01-01

    Age-related alterations in brain structure and function have been challenging to link to cognition due to potential overlapping influences of multiple neurobiological cascades. We examined multiple brain markers associated with age-related variation in cognition. Clinically normal older humans aged 65–90 from the Harvard Aging Brain Study (N = 186) were characterized on a priori magnetic resonance imaging markers of gray matter thickness and volume, white matter hyperintensities, fractional anisotropy (FA), resting-state functional connectivity, positron emission tomography markers of glucose metabolism and amyloid burden, and cognitive factors of processing speed, executive function, and episodic memory. Partial correlation and mediation analyses estimated age-related variance in cognition shared with individual brain markers and unique to each marker. The largest relationships linked FA and striatum volume to processing speed and executive function, and hippocampal volume to episodic memory. Of the age-related variance in cognition, 70–80% was accounted for by combining all brain markers (but only ∼20% of total variance). Age had significant indirect effects on cognition via brain markers, with significant markers varying across cognitive domains. These results suggest that most age-related variation in cognition is shared among multiple brain markers, but potential specificity between some brain markers and cognitive domains motivates additional study of age-related markers of neural health. PMID:25316342

  7. Multiple Brain Markers are Linked to Age-Related Variation in Cognition.

    PubMed

    Hedden, Trey; Schultz, Aaron P; Rieckmann, Anna; Mormino, Elizabeth C; Johnson, Keith A; Sperling, Reisa A; Buckner, Randy L

    2016-04-01

    Age-related alterations in brain structure and function have been challenging to link to cognition due to potential overlapping influences of multiple neurobiological cascades. We examined multiple brain markers associated with age-related variation in cognition. Clinically normal older humans aged 65-90 from the Harvard Aging Brain Study (N = 186) were characterized on a priori magnetic resonance imaging markers of gray matter thickness and volume, white matter hyperintensities, fractional anisotropy (FA), resting-state functional connectivity, positron emission tomography markers of glucose metabolism and amyloid burden, and cognitive factors of processing speed, executive function, and episodic memory. Partial correlation and mediation analyses estimated age-related variance in cognition shared with individual brain markers and unique to each marker. The largest relationships linked FA and striatum volume to processing speed and executive function, and hippocampal volume to episodic memory. Of the age-related variance in cognition, 70-80% was accounted for by combining all brain markers (but only ∼20% of total variance). Age had significant indirect effects on cognition via brain markers, with significant markers varying across cognitive domains. These results suggest that most age-related variation in cognition is shared among multiple brain markers, but potential specificity between some brain markers and cognitive domains motivates additional study of age-related markers of neural health.

  8. A basket two-part model to analyze medical expenditure on interdependent multiple sectors.

    PubMed

    Sugawara, Shinya; Wu, Tianyi; Yamanishi, Kenji

    2016-09-01

    This study proposes a novel statistical methodology to analyze expenditure on multiple medical sectors using consumer data. Conventionally, medical expenditure has been analyzed by two-part models, which separately consider purchase decision and amount of expenditure. We extend the traditional two-part models by adding the step of basket analysis for dimension reduction. This new step enables us to analyze complicated interdependence between multiple sectors without an identification problem. As an empirical application for the proposed method, we analyze data of 13 medical sectors from the Medical Expenditure Panel Survey. In comparison with the results of previous studies that analyzed the multiple sector independently, our method provides more detailed implications of the impacts of individual socioeconomic status on the composition of joint purchases from multiple medical sectors; our method has a better prediction performance.

  9. Microsatellite DNA markers applied to detection of multiple paternity in Caiman latirostris in Santa Fe, Argentina.

    PubMed

    Amavet, Patricia; Rosso, Esteban; Markariani, Rosa; Piña, Carlos Ignacio

    2008-12-01

    Detecting multiple paternity in wild populations of the broad-snouted caiman (Caiman latirostris) has important implications for conservation efforts. We have applied microsatellite markers to examine genetic variation in C. latirostris and also have provided the first data concerning detection of multiple paternity in wild populations of this species. Blood samples from four nest-guarding C. latirostris females and their hatchlings were obtained from Santa Fe Province, Argentina. Amplified products were analyzed by electrophoresis on 10% polyacrylamide gels and visualized with silver staining. Four out of the eight markers tested reliably amplified and yielded useful data. Using polyacrylamide gels with silver staining provides high enough resolution to obtain individual genotypes. In order to assess the presence or absence of more than two parents in each nest, we used the single locus Minimum Method, and applied Cervus 3.0 and Gerud 2.0 software in parentage analyses. Our results indicate more than one father in at least two families. This behavior could be the consequence of high habitat variability in the area where our population was sampled. The ability to understand mating systems is important for maintaining viable populations of exploited taxa like C. latirostris.

  10. Cancers Screening in an Asymptomatic Population by Using Multiple Tumour Markers.

    PubMed

    Wang, Hsin-Yao; Hsieh, Chia-Hsun; Wen, Chiao-Ni; Wen, Ying-Hao; Chen, Chun-Hsien; Lu, Jang-Jih

    2016-01-01

    Analytic measurement of serum tumour markers is one of commonly used methods for cancer risk management in certain areas of the world (e.g. Taiwan). Recently, cancer screening based on multiple serum tumour markers has been frequently discussed. However, the risk-benefit outcomes appear to be unfavourable for patients because of the low sensitivity and specificity. In this study, cancer screening models based on multiple serum tumour markers were designed using machine learning methods, namely support vector machine (SVM), k-nearest neighbour (KNN), and logistic regression, to improve the screening performance for multiple cancers in a large asymptomatic population. AFP, CEA, CA19-9, CYFRA21-1, and SCC were determined for 20 696 eligible individuals. PSA was measured in men and CA15-3 and CA125 in women. A variable selection process was applied to select robust variables from these serum tumour markers to design cancer detection models. The sensitivity, specificity, positive predictive value (PPV), negative predictive value, area under the curve, and Youden index of the models based on single tumour markers, combined test, and machine learning methods were compared. Moreover, relative risk reduction, absolute risk reduction (ARR), and absolute risk increase (ARI) were evaluated. To design cancer detection models using machine learning methods, CYFRA21-1 and SCC were selected for women, and all tumour markers were selected for men. SVM and KNN models significantly outperformed the single tumour markers and the combined test for men. All 3 studied machine learning methods outperformed single tumour markers and the combined test for women. For either men or women, the ARRs were between 0.003-0.008; the ARIs were between 0.119-0.306. Machine learning methods outperformed the combined test in analysing multiple tumour markers for cancer detection. However, cancer screening based solely on the application of multiple tumour markers remains unfavourable because of the

  11. FASMA: a service to format and analyze sequences in multiple alignments.

    PubMed

    Costantini, Susan; Colonna, Giovanni; Facchiano, Angelo M

    2007-12-01

    Multiple sequence alignments are successfully applied in many studies for under- standing the structural and functional relations among single nucleic acids and protein sequences as well as whole families. Because of the rapid growth of sequence databases, multiple sequence alignments can often be very large and difficult to visualize and analyze. We offer a new service aimed to visualize and analyze the multiple alignments obtained with different external algorithms, with new features useful for the comparison of the aligned sequences as well as for the creation of a final image of the alignment. The service is named FASMA and is available at http://bioinformatica.isa.cnr.it/FASMA/.

  12. Consensus genetic structuring and typological value of markers using multiple co-inertia analysis

    PubMed Central

    Laloë, Denis; Jombart, Thibaut; Dufour, Anne-Béatrice; Moazami-Goudarzi, Katayoun

    2007-01-01

    Working with weakly congruent markers means that consensus genetic structuring of populations requires methods explicitly devoted to this purpose. The method, which is presented here, belongs to the multivariate analyses. This method consists of different steps. First, single-marker analyses were performed using a version of principal component analysis, which is designed for allelic frequencies (%PCA). Drawing confidence ellipses around the population positions enhances %PCA plots. Second, a multiple co-inertia analysis (MCOA) was performed, which reveals the common features of single-marker analyses, builds a reference structure and makes it possible to compare single-marker structures with this reference through graphical tools. Finally, a typological value is provided for each marker. The typological value measures the efficiency of a marker to structure populations in the same way as other markers. In this study, we evaluate the interest and the efficiency of this method applied to a European and African bovine microsatellite data set. The typological value differs among markers, indicating that some markers are more efficient in displaying a consensus typology than others. Moreover, efficient markers in one collection of populations do not remain efficient in others. The number of markers used in a study is not a sufficient criterion to judge its reliability. "Quantity is not quality". PMID:17897596

  13. A two-step multiple-marker strategy for genome-wide association studies

    PubMed Central

    Aschard, Hugues; Guedj, Mickaël; Demenais, Florence

    2007-01-01

    Genome-wide association studies raise study-design and analytical issues that are still being debated. Among them, stands the issue of reducing the number of markers to be genotyped without loss of efficiency in identifying trait loci, which can reduce the cost of studies and minimize the multiple testing problem. With this aim, we proposed a two-step strategy based on two analytical methods suited to examine sets of markers rather than single markers: the local score, which screens the genome to select candidate regions in Step 1, and FBAT-LC, a multiple-marker family-based association test used to obtain significance levels of regions at step 2. The performance of this strategy was evaluated on all replicates of Genetic Analysis Workshop 15 Problem 3 simulated data, using the answers to that problem. Overall, seven of the nine generated trait loci were detected in at least 87% of the replicates using a framework designed to handle either association with the disease or association with the severity of disease. This multiple-marker strategy was compared to the single-marker approach. By considering regions instead of single markers, this strategy minimizes the multiple testing problem and the number of false-positive results. PMID:18466477

  14. Comparative usefulness of inflammatory markers to indicate bacterial infection-analyzed according to blood culture results and related clinical factors.

    PubMed

    Nishikawa, Hirokazu; Shirano, Michinori; Kasamatsu, Yu; Morimura, Ayumi; Iida, Ko; Kishi, Tomomi; Goto, Tetsushi; Okamoto, Saki; Ehara, Eiji

    2016-01-01

    To assess relationships of inflammatory markers and 2 related clinical factors with blood culture results, we retrospectively investigated inpatients' blood culture and blood chemistry findings that were recorded from January to December 2014 using electronic medical records and analyzed the data of 852 subjects (426 culture-positive and 426 culture-negative). Results suggested that the risk of positive blood culture statistically increased as inflammatory marker levels and the number of related factors increased. Concerning the effectiveness of inflammatory markers, when the outcome definition was also changed for C-reactive protein (CRP), the odds ratio had a similar value, whereas when the outcome definition of blood culture positivity was used for procalcitonin (PCT), the greatest effectiveness of that was detected. Therefore, the current results suggest that PCT is more useful than CRP as an auxiliary indication of bacterial infection.

  15. Stem cell marker nestin is expressed in plasma cells of multiple myeloma patients.

    PubMed

    Svachova, H; Pour, L; Sana, J; Kovarova, L; Raja, K R Muthu; Hajek, R

    2011-08-01

    Nestin is considered to be a characteristic marker of multipotent proliferative precursors found in some embryonic and fetal tissues. Its expression might be a suitable diagnostic and prognostic indicator of malignancy and a potential marker of cancer stem cells in solid tumors. Unexpectedly, nestin protein was detected in mature CD138(+)CD38(+) plasma cells of multiple myeloma patients and statistical analysis confirmed significant differences between myeloma patients and control group without hematological malignancy. Our results represent the first evidence of nestin expression in multiple myeloma. Further studies are required to elucidate the role of this protein in multiple myeloma. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Candidate gene molecular markers as tools for analyzing genetic susceptibility to Morbillivirus infection in stranded Cetaceans.

    PubMed

    Stejskalova, Karla; Bayerova, Zuzana; Futas, Jan; Hrazdilova, Kristyna; Klumplerova, Marie; Oppelt, Jan; Splichalova, Petra; Di Guardo, Giovanni; Mazzariol, Sandro; Di Francesco, Cristina Esmeralda; Di Francesco, Gabriella; Terracciano, Giuliana; Paiu, Romulus-Marian; Ursache, Teodor Dan; Modry, David; Horin, Petr

    2017-09-11

    Morbilliviruses, such as Cetacean morbillivirus (CeMV) or Phocine distemper virus (PDV), represent a growing threat for marine mammals on both hemispheres. Since free-ranging animal populations strongly rely on natural resistance mechanisms, innate immunity related genes and virus cell entry receptor genes may represent key factors involved in susceptibility to CeMV in Cetaceans. Using the next generation sequencing technology, we have sequenced eleven candidate genes in two model species, Stenella coeruleoalba and Phocoena phocoena. Suitable single nucleotide polymorphism markers of potential functional importance, located in genes coding for basigin (BSG, CD147), the signaling lymphocyte activating molecule (SLAMF1), the poliovirus related receptor-4 (NECTIN4, PVRL4), toll-like receptors 3,7,8 (TLR3, TLR7, TLR8), natural resistance-associated macrophage protein (SLC11A1) and natural cytotoxicity triggering receptor 1 (NCR1), were identified in each model species, along with MHC-DQB haplotypes unique for each species. This set of molecular markers represents a potentially useful tool for studying host genetic variation and susceptibility to Morbillivirus infection in Cetaceans as well as for studying functionally important genetic diversity of selected Cetacean populations. This article is protected by copyright. All rights reserved.

  17. Genetic diversity and structure in Bos taurus and Bos indicus populations analyzed by SNP markers.

    PubMed

    Lin, Bang Zhong; Sasazaki, Shinji; Mannen, Hideyuki

    2010-06-01

    The purpose of this study was to assess genetic diversity, phylogenetic relationship and population structure among nine Eurasian cattle populations using 58 single nucleotide polymorphism (SNP) markers. The calculated distribution of minor allele frequencies and heterozygosities suggested that the genetic diversity of Bos indicus populations was lower than that of Bos taurus populations. Phylogenetic analyses revealed the main divergence between the Bos taurus and Bos indicus populations, and subsequently between Asian and European populations. By principal components analysis, the Bos taurus and Bos indicus populations were clearly distinguished with PC1 (61.1%); however, six Bos taurus populations clustered loosely and the partial separation between European and Asian groups was observed by PC2 (12.5%). The structure analysis was performed using the STRUCTURE program. Distinct separation between Bos taurus and Bos indicus was shown at K = 2, and that between European and Asian populations at K = 3. At K = 4, 5 and 6, Mongolian population showed an admixture pattern with different ancestry of Asian and European cattle. At K = 7, all Bos taurus populations showed each cluster with little proportion of admixture. In conclusion, 58 SNP markers in this study could sufficiently estimate the genetic diversity, relationship and structure for nine Eurasian cattle populations, especially by analyses of principal components and STRUCTURE.

  18. Forensic Body Fluid Identification by Analysis of Multiple RNA Markers Using NanoString Technology

    PubMed Central

    Park, Jong-Lyul; Park, Seong-Min; Kim, Jeong-Hwan; Lee, Han-Chul; Lee, Seung-Hwan; Woo, Kwang-Man; Kim, Seon-Young

    2013-01-01

    RNA analysis has become a reliable method of body fluid identification for forensic use. Previously, we developed a combination of four multiplex quantitative PCR (qRT-PCR) probes to discriminate four different body fluids (blood, semen, saliva, and vaginal secretion). While those makers successfully identified most body fluid samples, there were some cases of false positive and negative identification. To improve the accuracy of the identification further, we tried to use multiple markers per body fluid and adopted the NanoString nCounter system instead of a multiplex qRT-PCR system. After measuring tens of RNA markers, we evaluated the accuracy of each marker for body fluid identification. For body fluids, such as blood and semen, each body fluid-specific marker was accurate enough for perfect identification. However, for saliva and vaginal secretion, no single marker was perfect. Thus, we designed a logistic regression model with multiple markers for saliva and vaginal secretion and achieved almost perfect identification. In conclusion, the NanoString nCounter is an efficient platform for measuring multiple RNA markers per body fluid and will be useful for forensic RNA analysis. PMID:24465241

  19. Forensic Body Fluid Identification by Analysis of Multiple RNA Markers Using NanoString Technology.

    PubMed

    Park, Jong-Lyul; Park, Seong-Min; Kim, Jeong-Hwan; Lee, Han-Chul; Lee, Seung-Hwan; Woo, Kwang-Man; Kim, Seon-Young

    2013-12-01

    RNA analysis has become a reliable method of body fluid identification for forensic use. Previously, we developed a combination of four multiplex quantitative PCR (qRT-PCR) probes to discriminate four different body fluids (blood, semen, saliva, and vaginal secretion). While those makers successfully identified most body fluid samples, there were some cases of false positive and negative identification. To improve the accuracy of the identification further, we tried to use multiple markers per body fluid and adopted the NanoString nCounter system instead of a multiplex qRT-PCR system. After measuring tens of RNA markers, we evaluated the accuracy of each marker for body fluid identification. For body fluids, such as blood and semen, each body fluid-specific marker was accurate enough for perfect identification. However, for saliva and vaginal secretion, no single marker was perfect. Thus, we designed a logistic regression model with multiple markers for saliva and vaginal secretion and achieved almost perfect identification. In conclusion, the NanoString nCounter is an efficient platform for measuring multiple RNA markers per body fluid and will be useful for forensic RNA analysis.

  20. Microsatellite markers reveal multiple origins for Italian weedy rice

    PubMed Central

    Grimm, Annabelle; Fogliatto, Silvia; Nick, Peter; Ferrero, Aldo; Vidotto, Francesco

    2013-01-01

    Weedy rice (Oryza sativa L.) is one of the major issues of rice cultivation worldwide. In Italy, it infests about 70% of the total rice area. Different Weedy Rice populations can be distinguished based on variable morphological and physiological traits; however, little is known about genetic differentiation and origin of Italian weedy rice populations. The objective of this study was to genetically and morphologically characterize and compare different Italian weedy rice populations selected on the basis of different phenotypes. The main Italian rice territory was divided into 10 geographical areas in which 40 weedy rice populations were collected and grouped according to the awn traits. All the individuals of the populations were morphologically characterized according to plant and seed traits. Genetic characterization was performed using 19 SSR markers on all the collected accessions, and several rice cultivars, including some very old (late 19th century), nowadays are no longer cultivated. ANOVA showed that morphological plant and seed traits were significantly affected by the collection area and awnedness group. The importance of the awn morphology was also reflected in the Bayesian clustering where, despite a relatively low genetic diversity, the clusters displayed different awn types. An UPGMA dendrogram confirmed the clusters detected in STRUCTURE analysis and also revealed a grouping of certain old cultivars with the weedy rice, suggesting a common origin. PMID:24363904

  1. Cellular superresolved imaging of multiple markers using temporally flickering nanoparticles

    PubMed Central

    Ilovitsh, Tali; Danan, Yossef; Meir, Rinat; Meiri, Amihai; Zalevsky, Zeev

    2015-01-01

    In this paper we present a technique aimed for simultaneous detection of multiple types of gold nanoparticles (GNPs) within a biological sample, using lock-in detection. We image the sample using a number of modulated laser beams that correspond to the number of GNP species that label a given sample. The final image where the GNPs are spatially separated is obtained computationally. The proposed method enables the simultaneous superresolved imaging of different areas of interest within biological sample and also the spatial separation of GNPs at sub-diffraction distances, making it a useful tool in the study of intracellular trafficking pathways in living cells. PMID:26020693

  2. Analysis of four PCR/SNaPshot multiplex assays analyzing 52 SNPforID markers.

    PubMed

    Goodwin, William; Alimat, Sharizah

    2017-04-01

    The SNPforID consortium identified a panel of 52 SNPs for forensic analysis that has been used by several laboratories worldwide. The original analysis of the 52 SNPs was based on a single multiplex reaction followed by two single-base-extension (SBE) reactions each of which was analyzed using capillary electrophoresis. The SBE assays were designed for high throughput genetic analyzers and were difficult to use on the single capillary ABI PRISM 310 Genetic Analyzer and the latest generation 3500 Genetic Analyzer, as sensitivity on the 310 was low and separation of products on the 3500 with POP-7™ was poor. We have modified the original assay and split it into four multiplex reactions, each followed by an SBE assay. These multiplex assays were analyzed using polymer POP-4™ on ABI 310 PRISM® and polymers POP-4™, POP-6™ and POP-7™ on the 3500 Genetic Analyzer. The assays were sensitive and reproducible with input DNA as low as 60 pg using both the ABI 310 and 3500. In addition, we found that POP-6™ was most effective with the 3500, based on the parameters that we assessed, achieving better separation of the small SBE products; this conflicted with the recommended use of POP-7™ by the instrument manufacturer. To support the use of the SNP panel in casework in Malaysia we have created an allele frequency database from 325 individuals, representing the major population groups within Malaysia. Population and forensic parameters were estimated for all populations and its efficacy evaluated using 51 forensic samples from challenging casework.

  3. Analyzing public inputs to multiple objective decisions on national forests using conjoint analysis

    Treesearch

    Donald F. Dennis

    1998-01-01

    Faced with multiple objectives, national forest managers and planners need a means to solicit and analyze public preferences and values. A conjoint ranking survey was designed to solicit public preferences for various levels of timber harvesting, wildlife habitats, hiking trails, snowmobile use, and off-road-vehicle (ORV) access on the Green Mountain National Forest....

  4. Cancers Screening in an Asymptomatic Population by Using Multiple Tumour Markers

    PubMed Central

    Wang, Hsin-Yao; Hsieh, Chia-Hsun; Wen, Chiao-Ni; Wen, Ying-Hao

    2016-01-01

    Background Analytic measurement of serum tumour markers is one of commonly used methods for cancer risk management in certain areas of the world (e.g. Taiwan). Recently, cancer screening based on multiple serum tumour markers has been frequently discussed. However, the risk–benefit outcomes appear to be unfavourable for patients because of the low sensitivity and specificity. In this study, cancer screening models based on multiple serum tumour markers were designed using machine learning methods, namely support vector machine (SVM), k-nearest neighbour (KNN), and logistic regression, to improve the screening performance for multiple cancers in a large asymptomatic population. Methods AFP, CEA, CA19-9, CYFRA21-1, and SCC were determined for 20 696 eligible individuals. PSA was measured in men and CA15-3 and CA125 in women. A variable selection process was applied to select robust variables from these serum tumour markers to design cancer detection models. The sensitivity, specificity, positive predictive value (PPV), negative predictive value, area under the curve, and Youden index of the models based on single tumour markers, combined test, and machine learning methods were compared. Moreover, relative risk reduction, absolute risk reduction (ARR), and absolute risk increase (ARI) were evaluated. Results To design cancer detection models using machine learning methods, CYFRA21-1 and SCC were selected for women, and all tumour markers were selected for men. SVM and KNN models significantly outperformed the single tumour markers and the combined test for men. All 3 studied machine learning methods outperformed single tumour markers and the combined test for women. For either men or women, the ARRs were between 0.003–0.008; the ARIs were between 0.119–0.306. Conclusion Machine learning methods outperformed the combined test in analysing multiple tumour markers for cancer detection. However, cancer screening based solely on the application of multiple tumour

  5. Application of ISSR markers to analyze molecular relationships in Iranian jasmine (Jasminum spp.) accessions.

    PubMed

    Ghasemi Ghehsareh, Masood; Salehi, Hassan; Khosh-Khui, Morteza; Niazi, Ali

    2015-01-01

    There are many species of jasmines in different regions of Iran in natural or cultivated form, and there is no information about their genetic status. Therefore, inter-simple sequence repeat (ISSR) analysis was used to evaluate genetic variations of the 53 accessions representing eight species of Jasminum collected from different regions of Iran. A total of 21 ISSR primers were used which generated 981 bands of different sizes. Mean percentage of polymorphic bands was 90.64 %. Maximum resolving power, polymorphic information content average, and marker index values were 21.55, 0.35, and 14.42 for primers of 3, 4, and 3 respectively. The unweighted pair group method with arithmetic mean dendrogram based on Jaccard's coefficients indicated that 53 accessions were divided into two major clusters. The first major cluster was divided into two subclusters; the subcluster A included Jasminum grandiflorum L., J. officinale L., and J. azoricum L. and the subcluster B consisted of three forms of J. sambac L. (single, semi-double, and double flowers). The second major cluster was divided into two subclusters; the first subcluster (C) included J. humile L., J. primulinum Hemsl., J. nudiflorum Lindl. and the second subcluster (D) consisted of J. fruticans L. At the species level, the highest percentage of polymorphism (34.05 %), numbers of effective alleles (1.16), Shannon index (0.151), and Nei's genetic diversity (0.098) were observed in J. officinale. The lowest values of percentage polymorphism (0.011), number of effective alleles (1.009), Shannon index (0.007), and Nei's genetic diversity (0.005) were obtained for J. nudiflorum. Based on pairwise population matrix of Nei's unbiased genetic identity, the highest identity (0.85) was found between J.officinale and J. azoricum and the lowest identity (0.69) was between J. grandiflorum and J. perimulinum. Based on analysis of molecular variance, the amount of genetic variations among the eight populations was 83 %. This study

  6. Statistical methods for analysis of coordination of chest wall motion using optical reflectance imaging of multiple markers

    NASA Astrophysics Data System (ADS)

    Kenyon, C. M.; Ghezzo, R. H.; Cala, S. J.; Ferrigno, Giancarlo; Pedotti, Antonio; Macklem, P. T.; Rochester, D. F.

    1994-07-01

    To analyze coordination of chest wall motion we have used principle component analysis (PCA) and multiple regression analysis (MRA) with respect to spirometry on the displacements of 93 optical reflective markers placed upon the chest wall (CW). Each marker is tracked at 10 Hz with an accuracy of 0.2 mm in each spatial dimension using the ELITE system (IEEE Trans. Biomed. Eng. 11:943-949, 1985). PCA enables the degree of linear coordination between all of the markers to be assessed using the eigenvectors and eigenvalues of the covariance of the matrix of marker displacements in each dimension against time. Thus the number of linear degrees of freedom (DOF) which contribute more than a particular amount to the total variance can be determined and analyzed. MRA with respect to spirometrically measured lung volume changes enables identification of the CW points whose movement correlates best with lung volume. We have used this analysis to compare a quiet breathing sequence with one where tidal volume was increased fourfold involuntarily and show that the number of DOF with eigenvalues accounting for >5% of the covariance increased from 2 to 3. Also the point whose movement correlated best with lung volume changed from halfway down the lower costal margin to a more lateral point at the level of the bottom of the sternum. This quantification of CW coordination may be useful in analysis and staging of many respiratory disorders and is applicable to any nonrigid body motion where points can be tracked.

  7. Markers

    ERIC Educational Resources Information Center

    Healthy Schools Network, Inc., 2011

    2011-01-01

    Dry erase whiteboards come with toxic dry erase markers and toxic cleaning products. Dry erase markers labeled "nontoxic" are not free of toxic chemicals and can cause health problems. Children are especially vulnerable to environmental health hazards; moreover, schools commonly have problems with indoor air pollution, as they are more densely…

  8. Hypodiploid multiple myeloma is characterized by more aggressive molecular markers than non-hyperdiploid multiple myeloma

    PubMed Central

    Van Wier, Scott; Braggio, Esteban; Baker, Angela; Ahmann, Gregory; Levy, Joan; Carpten, John D.; Fonseca, Rafael

    2013-01-01

    Multiple myeloma can be categorized into hyperdiploid or non-hyperdiploid myeloma based on the number of chromosomes found in the tumor clone. Among the non-hyperdiploid myelomas, the hypodiploid subtype has the most aggressive clinical phenotype, but the genetic differences between groups are not completely defined. In order to understand the genetic background of hypodiploid multiple myeloma better, we compared the genomic (array-based comparative genomic hybridization) and transcriptomic (gene expression profiling) background of 49 patients with hypodiploid myeloma with 50 other non-hyperdiploid and 125 hyperdiploid myeloma patients. There were significant chromosomal and gene expression differences between hyperdiploid patients and non-hyperdiploid and hypodiploid patients. Non-hyperdiploid and hypodiploid patients shared most of the chromosomal abnormalities; nevertheless a subset of these abnormalities, such as monosomies 13, 14 and 22, was markedly increased in hypodiploid patients. Furthermore, deletions of 1p, 12p, 16q and 17p, all associated with poor outcome or progression in multiple myeloma, were significantly enriched in hypodiploid patients. Molecular risk-stratification indices reinforce the worse prognosis associated with hypodiploid multiple myeloma compared with non-hyperdiploid multiple myeloma. Gene expression profiling clustered hypodiploid and non-hyperdiploid subgroups closer than hyperdiploid myeloma but also highlighted the up-regulation of CCND2, WHSC1/MMSET and FGFR3 in the hypodiploid subtype. In summary, hypodiploid multiple myeloma is genetically similar to non-hyperdiploid multiple myeloma but characterized by a higher prevalence of genetic alterations associated with poor outcome and disease progression. It is provocative to hypothesize that hypodiploid multiple myeloma is an advanced stage of non-hyperdiploid multiple myeloma. PMID:23716545

  9. Multiple Mass Analysis Using an Ion Trap Array (ITA) Mass Analyzer

    NASA Astrophysics Data System (ADS)

    Xiao, Yu; Chu, Yanqiu; Ling, Xing; Ding, Zhengzhi; Xu, Chongsheng; Ding, Li; Ding, Chuan-Fan

    2013-09-01

    A novel ion trap array (ITA) mass analyzer with six ion trapping and analyzing channels was investigated. It is capable of analyzing multiple samples simultaneously. The ITA was built with several planar electrodes made of stainless steel and 12 identical parallel zirconia ceramic substrates plated with conductive metal layers. Each two of the opposing ceramic electrode plates formed a boundary of an ion trap channel and six identical ion trapping and analyzing channels were placed in parallel without physical electrode between any two adjacent channels. The electric field distribution inside each channel was studied with simulation. The new design took the advantage of high precision machining attributable to the rigidity of ceramic, and the convenience of surface patterning technique. The ITA system was tested by using a two-channel electrospray ionization source, a multichannel simultaneous quadruple ion guide, and two detectors. The simultaneous analysis of two different samples with two adjacent ITA channels was achieved and independent mass spectra were obtained. For each channel, the mass resolution was tested. Additional ion trap functions such as mass-selected ion isolation and collision-induced dissociation (CID) were also tested. The results show that one ITA is well suited for multiple simultaneous mass analyses.

  10. Circulating osteopontin: a dual marker of bone destruction and angiogenesis in patients with multiple myeloma

    PubMed Central

    2011-01-01

    The matrix protein osteopontin has been shown to be a marker of osteoclastic activity in multiple myeloma patients, as well as a regulator of angiogenesis. We measured serum levels of osteopontin in 50 untreated multiple myeloma patients (in 25, also after treatment) and examined the relation to markers of osteolytic and angiogenic activity. The median (range) of serum osteopontin was 85 (5-232) in the patient group vs. 36 (2-190) ng/ml in the control group. Serum osteopontin levels were significantly higher in patients with advanced stage or grade of myeloma disease. All patients with serum osteopontin levels >100 ng/ml had advanced stage (II or III) or high grade bone disease, whereas stage I or low grade patients had serum osteopontin levels <100ng/ml. Serum osteopontin levels significantly decreased after treatment. There was a positive correlation of osteopontin with the bone turnover marker N-terminal propeptide of procollagen type I (NTx) and the angiogenic markers vascular endothelial growth factor (VEGF) and bone marrow microvessel density (r: 0.35, 0.47 and 0.30 respectively, p < 0.05). These results support osteopontin as a dual marker of bone destruction and angiogenic activity in myeloma patients. Osteopontin represents a useful biomarker for monitoring myeloma disease activity. PMID:21548993

  11. Highly sensitive detection of multiple tumor markers for lung cancer using gold nanoparticle probes and microarrays.

    PubMed

    Gao, Wanlei; Wang, Wentao; Yao, Shihua; Wu, Shan; Zhang, Honglian; Zhang, Jishen; Jing, Fengxiang; Mao, Hongju; Jin, Qinghui; Cong, Hui; Jia, Chunping; Zhang, Guojun; Zhao, Jianlong

    2017-03-15

    Assay of multiple serum tumor markers such as carcinoembryonic antigen (CEA), cytokeratin 19 fragment antigen (CYFRA21-1), and neuron specific enolase (NSE), is important for the early diagnosis of lung cancer. Dickkopf-1 (DKK1), a novel serological and histochemical biomarker, was recently reported to be preferentially expressed in lung cancer. Four target proteins were sandwiched by capture antibodies attached to microarrays and detection antibodies carried on modified gold nanoparticles. Optical signals generated by the sandwich structures were amplified by gold deposition with HAuCl4 and H2O2, and were observable by microscopy or the naked eye. The four tumor markers were subsequently measured in 106 lung cancer patients and 42 healthy persons. The assay was capable of detecting multiple biomarkers in serum sample at concentration of <1 ng mL(-1) in 1 h. Combined detection of the four tumor markers highly improved the sensitivity (to 87.74%) for diagnosis of lung cancer compared with sensitivity of single markers. A rapid, highly sensitive co-detection method for multiple biomarkers based on gold nanoparticles and microarrays was developed. In clinical use, it would be expected to improve the early diagnosis of lung cancer.

  12. Precision of methods for calculating identity-by-descent matrices using multiple markers

    PubMed Central

    Sørensen, Anders Christian; Pong-Wong, Ricardo; Windig, Jack J; Woolliams, John A

    2002-01-01

    A rapid, deterministic method (DET) based on a recursive algorithm and a stochastic method based on Markov Chain Monte Carlo (MCMC) for calculating identity-by-descent (IBD) matrices conditional on multiple markers were compared using stochastic simulation. Precision was measured by the mean squared error (MSE) of the relationship coefficients in predicting the true IBD relationships, relative to MSE obtained from using pedigree only. Comparisons were made when varying marker density, allele numbers, allele frequencies, and the size of full-sib families. The precision of DET was 75–99% relative to MCMC, but was not simply related to the informativeness of individual loci. For situations mimicking microsatellite markers or dense SNP, the precision of DET was ≥ 95% relative to MCMC. Relative precision declined for the SNP, but not microsatellites as marker density decreased. Full-sib family size did not affect the precision. The methods were tested in interval mapping and marker assisted selection, and the performance was very largely determined by the MSE. A multi-locus information index considering the type, number, and position of markers was developed to assess precision. It showed a marked empirical relationship with the observed precision for DET and MCMC and explained the complex relationship between relative precision and the informativeness of individual loci. PMID:12427386

  13. Analyzing Multiple Multivariate Time Series Data Using Multilevel Dynamic Factor Models.

    PubMed

    Song, Hairong; Zhang, Zhiyong

    2014-01-01

    Multivariate time series data offer researchers opportunities to study dynamics of various systems in social and behavioral sciences. Dynamic factor model (DFM), as an idiographic approach for studying intraindividual variability and dynamics, has typically been applied to time series data obtained from a single unit. When multivariate time series data are collected from multiple units, how to synchronize dynamical information becomes a silent issue. To address this issue, the current study presented a multilevel dynamic factor model (MDFM) that analyzes multiple multivariate time series in multilevel SEM frameworks. MDFM not only disentangles within- and between-person variability but also models dynamics of the intraindividual processes. To illustrate the uses of MDFMs, we applied lag0, lag1, and lag2 MDFMs to empirical data on affect collected from 205 dating couples who had at least 50 consecutive days of observations. We also considered a model extension where the dynamical coefficients were allowed to be randomly varying in the population. The empirical analysis yielded interesting findings regarding affect regulation and coregulation within couples, demonstrating promising uses of MDFMs in analyzing multiple multivariate time series. In the end, we discussed a number of methodological issues in the applications of MDFMs and pointed out possible directions for future research.

  14. Multiple Markers of Inflammation and Weight Status: Cross-sectional Analyses Throughout Childhood

    PubMed Central

    Skinner, Asheley Cockrell; Steiner, Michael J.; Henderson, Frederick W.; Perrin, Eliana M.

    2010-01-01

    OBJECTIVE Inflammatory markers such as C-reactive protein (CRP) are related to obesity in adults, but the association is less clear in children. Our objective was to examine relationships between multiple markers of inflammation and children’s weight status; we hypothesized that the prevalence of inflammatory markers would increase as weight status increased. METHODS We conducted a cross-sectional analysis of children in the United States aged 1 to 17 years in the National Health and Nutrition Examination Survey, 1999–2006. Children were categorized using weight-for-length when age < 2 years and BMI for ≥2 years, as very obese (≥99th percentile), obese (< 99th and ≥95th percentile), overweight (< 95th and ≥85th percentile), and healthy weight (> 5th to ≤85 thpercentile)according to expert consensus. Our main outcome measures were high-sensitivity CRP and absolute neutrophil count, in addition to a novel third measure: ferritin controlled for iron status using a ferritin/transferrin ratio. We used Cox proportional hazards models to examine risk of abnormal values of inflammatory markers according to weight. RESULTS Increased risk of a CRP level of > 1.0 mg/L was evident among very obese children from ages 3 to 5 years (hazard ratio [HR]: 2.29; P < .01) through 15 to 17 years (HR: 4.73; P < .01). Increased risk of abnormal neutrophil count among very obese children began at 6 to 8 years (HR: 2.00; P = .049), and increased prevalence of abnormal ferritin/transferrin ratio began at 9 to 11 years (HR: 7.06; P < .001). CONCLUSIONS Multiple inflammatory markers are strongly and positively associated with increasing weight status in children, and this relationship starts as young as age 3. Elevated inflammatory markers in very young obese children are particularly concerning, because inflammation may cause long-term, cumulative vascular damage. This deserves additional research via longitudinal design. PMID:20194272

  15. Population structure and genetic diversity in insular populations of Nasutitermes takasagoensis (Isoptera: Termitidae) analyzed by AFLP markers.

    PubMed

    García, Julio; Maekawa, Kiyoto; Miura, Toru; Matsumoto, Tadao

    2002-10-01

    Dispersal ability and degree of inbreeding in a population can indirectly be assessed using genetic markers. In general, it was suggested that winged termites are not able to fly distances greater than several hundred meters. Here, amplified fragment length polymorphism (AFLP) was used to analyze genetic diversity, population substructure, and gene flow among insular populations of the termite Nasutitermes takasagoensis (Isoptera: Termitidae) in the Yaeyama Islands, Okinawa, Japan. Samples were collected from 77 nests on seven islands of the Yaeyama Group. Using three primer combinations a total of 155 bands were generated with 78 (50%) polymorphic bands. Genetic distance and G(st) values among insular populations were calculated. Relatively high genetic diversity and low values of G (st), suggest there is moderate subpopulation structure. Based on these results, we discussed two possibilities; first, winged termites are able to fly over distances of several kilometers, and second, these results were obtained because insular populations share a recent common origin.

  16. Detection of multiple tumor markers using ultra-long carbon nanotube devices

    NASA Astrophysics Data System (ADS)

    So, Hye-Mi; Park, Dong-Won; Kim, Beom Soo; Kong, Ki-Jeong; Buh, Gyoung-Ho; Chang, Hyunju; Lee, Jeong-O.; Kong, Jing

    2008-03-01

    For the simultaneous detection of multiple tumor markers, we have fabricated ultra-long carbon nanotube sensors that can detect carcinoembryonic antigen (CEA) and prostate specific antigen (PSA), simultaneously. Ultra-long carbon nanotubes, several millimeters long, were grown by ethanol CVD, and fabricated as FET sensors by using conventional photolithography. To functionalize each segment of a single ultra-long nanotube device with multiple-tumor markers, we first functionalize the entire device with CDI-Tween 20 linking molecules, and then immobilized CEA and PSA antibodies using the microfluidic channel. The electrical conductance from CEA-antibody functionalized and PSA-antibody functionalized segment of a ultra-long carbon nanotube device was monitored simultaneously with Ag/AgCl reference electrode as a liquid gate. We will discuss the advantages of long-nanotube device in detail.

  17. Association of Genetic Markers with CSF Oligoclonal Bands in Multiple Sclerosis Patients

    PubMed Central

    Esposito, Federica; Lucenti, Ausiliatrice; Harbo, Hanne F.; Goris, An; Kockum, Ingrid; Oturai, Annette Bang; Celius, Elisabeth Gulowsen; Mero, Inger L.; Dubois, Bénédicte; Olsson, Tomas; Søndergaard, Helle Bach; Cusi, Daniele; Lupoli, Sara; Andreassen, Bettina Kulle; Myhr, Kjell-Morten; Guerini, Franca R.; Comi, Giancarlo

    2013-01-01

    Objective to explore the association between genetic markers and Oligoclonal Bands (OCB) in the Cerebro Spinal Fluid (CSF) of Italian Multiple Sclerosis patients. Methods We genotyped 1115 Italian patients for HLA-DRB1*15 and HLA-A*02. In a subset of 925 patients we tested association with 52 non-HLA SNPs associated with MS susceptibility and we calculated a weighted Genetic Risk Score. Finally, we performed a Genome Wide Association Study (GWAS) with OCB status on a subset of 562 patients. The best associated SNPs of the Italian GWAS were replicated in silico in Scandinavian and Belgian populations, and meta-analyzed. Results HLA-DRB1*15 is associated with OCB+: p = 0.03, Odds Ratio (OR) = 1.6, 95% Confidence Limits (CL) = 1.1–2.4. None of the 52 non-HLA MS susceptibility loci was associated with OCB, except one SNP (rs2546890) near IL12B gene (OR: 1.45; 1.09–1.92). The weighted Genetic Risk Score mean was significantly (p = 0.0008) higher in OCB+ (7.668) than in OCB− (7.412) patients. After meta-analysis on the three datasets (Italian, Scandinavian and Belgian) for the best associated signals resulted from the Italian GWAS, the strongest signal was a SNP (rs9320598) on chromosome 6q (p = 9.4×10−7) outside the HLA region (65 Mb). Discussion genetic factors predispose to the development of OCB. PMID:23785401

  18. Neurite dispersion: a new marker of multiple sclerosis spinal cord pathology?

    PubMed

    Grussu, Francesco; Schneider, Torben; Tur, Carmen; Yates, Richard L; Tachrount, Mohamed; Ianuş, Andrada; Yiannakas, Marios C; Newcombe, Jia; Zhang, Hui; Alexander, Daniel C; DeLuca, Gabriele C; Gandini Wheeler-Kingshott, Claudia A M

    2017-09-01

    Conventional magnetic resonance imaging (MRI) of the multiple sclerosis spinal cord is limited by low specificity regarding the underlying pathological processes, and new MRI metrics assessing microscopic damage are required. We aim to show for the first time that neurite orientation dispersion (i.e., variability in axon/dendrite orientations) is a new biomarker that uncovers previously undetected layers of complexity of multiple sclerosis spinal cord pathology. Also, we validate against histology a clinically viable MRI technique for dispersion measurement (neurite orientation dispersion and density imaging, NODDI), to demonstrate the strong potential of the new marker. We related quantitative metrics from histology and MRI in four post mortem spinal cord specimens (two controls; two progressive multiple sclerosis cases). The samples were scanned at high field, obtaining maps of neurite density and orientation dispersion from NODDI and routine diffusion tensor imaging (DTI) indices. Histological procedures provided markers of astrocyte, microglia, myelin and neurofilament density, as well as neurite dispersion. We report from both NODDI and histology a trend toward lower neurite dispersion in demyelinated lesions, indicative of reduced neurite architecture complexity. Also, we provide unequivocal evidence that NODDI-derived dispersion matches its histological counterpart (P < 0.001), while DTI metrics are less specific and influenced by several biophysical substrates. Neurite orientation dispersion detects a previously undescribed and potentially relevant layer of microstructural complexity of multiple sclerosis spinal cord pathology. Clinically feasible techniques such as NODDI may play a key role in clinical trial and practice settings, as they provide histologically meaningful dispersion indices.

  19. IPAT: a freely accessible software tool for analyzing multiple patent documents with inbuilt landscape visualizer.

    PubMed

    Ajay, Dara; Gangwal, Rahul P; Sangamwar, Abhay T

    2015-01-01

    Intelligent Patent Analysis Tool (IPAT) is an online data retrieval tool, operated based on text mining algorithm to extract specific patent information in a predetermined pattern into an Excel sheet. The software is designed and developed to retrieve and analyze technology information from multiple patent documents and generate various patent landscape graphs and charts. The software is C# coded in visual studio 2010, which extracts the publicly available patent information from the web pages like Google Patent and simultaneously study the various technology trends based on user-defined parameters. In other words, IPAT combined with the manual categorization will act as an excellent technology assessment tool in competitive intelligence and due diligence for predicting the future R&D forecast.

  20. A simple and rapid method for calculating identity-by-descent matrices using multiple markers.

    PubMed

    Pong-Wong, R; George, A W; Woolliams, J A; Haley, C S

    2001-01-01

    A fast, partly recursive deterministic method for calculating Identity-by-Descent (IBD) probabilities was developed with the objective of using IBD in Quantitative Trait Locus (QTL) mapping. The method combined a recursive method for a single marker locus with a method to estimate IBD between sibs using multiple markers. Simulated data was used to compare the deterministic method developed in the present paper with a stochastic method (LOKI) for precision in estimating IBD probabilities and performance in the task of QTL detection with the variance component approach. This comparison was made in a variety of situations by varying family size and degree of polymorphism among marker loci. The following were observed for the deterministic method relative to MCMC: (i) it was an order of magnitude faster; (ii) its estimates of IBD probabilities were found to agree closely, even though it does not extract information when haplotypes are not known with certainty; (iii) the shape of the profile for the QTL test statistic as a function of location was similar, although the magnitude of the test statistic was slightly smaller; and (iv) the estimates of QTL variance was similar. It was concluded that the method proposed provided a rapid means of calculating the IBD matrix with only a small loss in precision, making it an attractive alternative to the use of stochastic MCMC methods. Furthermore, developments in marker technology providing denser maps would enhance the relative advantage of this method.

  1. A simple and rapid method for calculating identity-by-descent matrices using multiple markers

    PubMed Central

    Pong-Wong, Ricardo; George, Andrew Winston; Woolliams, John Arthur; Haley, Chris Simon

    2001-01-01

    A fast, partly recursive deterministic method for calculating Identity-by-Descent (IBD) probabilities was developed with the objective of using IBD in Quantitative Trait Locus (QTL) mapping. The method combined a recursive method for a single marker locus with a method to estimate IBD between sibs using multiple markers. Simulated data was used to compare the deterministic method developed in the present paper with a stochastic method (LOKI) for precision in estimating IBD probabilities and performance in the task of QTL detection with the variance component approach. This comparison was made in a variety of situations by varying family size and degree of polymorphism among marker loci. The following were observed for the deterministic method relative to MCMC: (i) it was an order of magnitude faster; (ii) its estimates of IBD probabilities were found to agree closely, even though it does not extract information when haplotypes are not known with certainty; (iii) the shape of the profile for the QTL test statistic as a function of location was similar, although the magnitude of the test statistic was slightly smaller; and (iv) the estimates of QTL variance was similar. It was concluded that the method proposed provided a rapid means of calculating the IBD matrix with only a small loss in precision, making it an attractive alternative to the use of stochastic MCMC methods. Furthermore, developments in marker technology providing denser maps would enhance the relative advantage of this method. PMID:11712969

  2. CUL4A as a marker and potential therapeutic target in multiple myeloma.

    PubMed

    Yang, Yougang; Wang, Shanan; Li, Jinghong; Qi, Shipeng; Zhang, Debing

    2017-07-01

    Multiple myeloma is the most common cause of death of hematological malignancy worldwide. Cullin 4A has been proposed as oncogene in several types of human cancer, but the expression and function of cullin 4A in multiple myeloma remain unclear. Here, we demonstrate that cullin 4A plays an oncogenic role in multiple myeloma development. The expression of cullin 4A was detected by quantitative real-time polymerase chain reaction in multiple myeloma patients and multiple myeloma cell lines. In addition, silencing of cullin 4A with small interfering RNA was performed in human multiple myeloma cells, and the impact on proliferation, cell cycle, apoptosis, migration, and invasion of the multiple myeloma cells was analyzed. We found that the level of cullin 4A in serum samples was significantly upregulated in patients with multiple myeloma compared with healthy control subjects. Knockdown of cullin 4A via small interfering RNA inhibited the proliferation of the multiple myeloma cell lines by delaying cell-cycle progression and increasing apoptosis. cullin 4A downregulation inhibited multiple myeloma cell migration and invasion in vitro. Our results suggested that cullin 4A could be a promising therapy target in multiple myeloma patients.

  3. Molecular and biologic markers of progression in monoclonal gammopathy of undetermined significance to multiple myeloma.

    PubMed

    Mailankody, Sham; Mena, Esther; Yuan, Constance M; Balakumaran, Arun; Kuehl, W Michael; Landgren, Ola

    2010-12-01

    Multiple myeloma (MM) is a malignant plasma cell dyscrasia localized in the bone marrow. Recent studies have shown that MM is preceded in virtually all cases by a premalignant state called monoclonal gammopathy of undetermined significance (MGUS). This review focuses on non-IgM MGUS and its progression to MM. Although certain clinical markers of MGUS progression have been identified, it currently is not possible to accurately determine individual risk of progression. This review focuses on the various biologic and molecular markers that could be used to determine the risk of MM progression. A better understanding of the pathogenesis will allow us to define the biological high-risk precursor disease and, ultimately, to develop early intervention strategies designed to delay and prevent full-blown MM.

  4. Use of multi-InDels as novel markers to analyze 13 X-chromosome haplotype loci for forensic purposes.

    PubMed

    Fan, Guangyao; Ye, Yi; Luo, Haibo; Hou, Yiping

    2015-12-01

    Many studies have been proposed to identify insertion/deletion (InDel) polymorphisms in humans for forensic genetic studies. However, the discriminatory power of InDels is limited by the poor polymorphisms of diallelic markers. To improve their discriminatory power, we developed multi-InDel, a novel autosomal marker comprising more than two InDel loci that are tightly linked by their physical position and combined into a specific marker by a pair of PCR primers. This strategy gives at least three haplotypes for each multi-InDel marker. Such markers can be potentially very useful in forensic applications. In this study, we focused on multi-InDel markers located on X chromosome (ChrX). A multiplex system with 13 multi-InDel markers, including 28 InDel loci in ChrX, was developed. To validate the multi-InDel panel, the haplotype distribution in a population sample and in a set of pedigrees was investigated. This study demonstrates usefulness of these markers for individual identification and relationship studies. We highlight the fact that the multi-InDel markers located on ChrX can provide new supporting information for complex kinship testing. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Multiple Small Supernumerary Marker Chromosomes Resulting from Maternal Meiosis I or II Errors

    PubMed Central

    Hochstenbach, Ron; Nowakowska, Beata; Volleth, Marianne; Ummels, Amber; Kutkowska-Kaźmierczak, Anna; Obersztyn, Ewa; Ziemkiewicz, Kamila; Gerloff, Claudia; Schanze, Denny; Zenker, Martin; Muschke, Petra; Schanze, Ina; Poot, Martin; Liehr, Thomas

    2016-01-01

    We present 2 cases with multiple de novo supernumerary marker chromosomes (sSMCs), each derived from a different chromosome. In a prenatal case, we found mosaicism for an sSMC(4), sSMC(6), sSMC(9), sSMC(14) and sSMC(22), while a postnatal case had an sSMC(4), sSMC(8) and an sSMC(11). SNP-marker segregation indicated that the sSMC(4) resulted from a maternal meiosis II error in the prenatal case. Segregation of short tandem repeat markers on the sSMC(8) was consistent with a maternal meiosis I error in the postnatal case. In the latter, a boy with developmental/psychomotor delay, autism, hyperactivity, speech delay, and hypotonia, the sSMC(8) was present at the highest frequency in blood. By comparison to other patients with a corresponding duplication, a minimal region of overlap for the phenotype was identified, with CHRNB3 and CHRNA6 as dosage-sensitive candidate genes. These genes encode subunits of nicotinic acetylcholine receptors (nAChRs). We propose that overproduction of these subunits leads to perturbed component stoichiometries with dominant negative effects on the function of nAChRs, as was shown by others in vitro. With the limitation that in each case only one sSMC could be studied, our findings demonstrate that different meiotic errors lead to multiple sSMCs. We relate our findings to age-related aneuploidy in female meiosis and propose that predivision sister-chromatid separation during meiosis I or II, or both, may generate multiple sSMCs. PMID:26997941

  6. Multivariate and integrative approach to analyze multiple biomarkers in ecotoxicology: A field study in Neotropical region.

    PubMed

    Ghisi, Nédia C; Oliveira, Elton C; Guiloski, Izonete C; de Lima, Sonia Barbosa; Silva de Assis, Helena C; Longhi, Solon Jonas; Prioli, Alberto J

    2017-12-31

    Aquatic pollution has dramatically worsened in developing countries, due to the discharge of a mixture of pollutants into water bodies, to the lack of stringent laws, and the inadequate treatment of effluents. In this study, the Neotropical fish Astyanax aff. paranae was sampled from three sites with different pollution levels: 1) a Biological Reserve (Rebio), protected by the Brazilian government; 2) an agricultural area in one of the most productive regions of Brazil, upstream of an urban zone; and 3) a site downstream from urban zone, characterized by the influx of different effluents, including wastes from industry, a sewer treatment plant, and agricultural areas. We assess biomarkers at multiple levels, such as the comet assay, hepatic histopathological analysis, brain and muscle acetylcholinesterase (AChE) and the hepatic enzymes glutathione-S-transferase (GST), catalase (CAT), and lipoperoxidation (LPO), during winter and summer. The interpretation of field results is always a very complex operation, since many factors can influence the variables analyzed in uncontrollable conditions. For this reason, we apply an integrative multivariate analysis. The results showed that the environmental risk of the three sites was significantly different. We can see a gradient in data distribution in discriminant analysis: separating, from one side, the fish of Rebio; in the middle are the fish from agricultural area and, in the other side are the animals from downstream site. Overall, the biomarkers responses were more greatly altered in the downstream site, whereas fish from the agricultural area showed an intermediate level of damage. The greatest changes were likely caused by agriculture, industrial chemical effluents and ineffective sewage treatments, in a synergic interaction in downstream site. In conclusion, the use of multiple biomarkers at different response levels to assess the toxic effects of mixed pollutants in a natural aquatic environment is an important

  7. Efficient development of highly polymorphic microsatellite markers based on polymorphic repeats in transcriptome sequences of multiple individuals.

    PubMed

    Vukosavljev, M; Esselink, G D; van 't Westende, W P C; Cox, P; Visser, R G F; Arens, P; Smulders, M J M

    2015-01-01

    The first hurdle in developing microsatellite markers, cloning, has been overcome by next-generation sequencing. The second hurdle is testing to differentiate polymorphic from nonpolymorphic loci. The third hurdle, somewhat hidden, is that only polymorphic markers with a large effective number of alleles are sufficiently informative to be deployed in multiple studies. Both steps are laborious and still performed manually. We have developed a strategy in which we first screen reads from multiple genotypes for repeats that show the most length variants, and only these are subsequently developed into markers. We validated our strategy in tetraploid garden rose using Illumina paired-end transcriptome sequences of 11 roses. Of 48 tested two markers failed to amplify, but all others were polymorphic. Ten loci amplified more than one locus, indicating duplicated genes or gene families. Completely avoiding duplicated loci will be difficult because the range of numbers of predicted alleles of highly polymorphic single- and multilocus markers largely overlapped. Of the remainder, half were replicate markers (i.e. multiple primer pairs for one locus), indicating the difficulty of correctly filtering short reads containing repeat sequences. We subsequently refined the approach to eliminate multiple primer sets to the same loci. The remaining 18 markers were all highly polymorphic, amplifying on average 11.7 alleles per marker (range = 6-20) in 11 tetraploid roses, exceeding the 8.2 alleles per marker of the 24 most polymorphic markers genotyped previously. This strategy therefore represents a major step forward in the development of highly polymorphic microsatellite markers.

  8. Analysis of multiple enteric viral targets as sewage markers in coral reefs.

    PubMed

    Lipp, Erin K; Futch, J Carrie; Griffin, Dale W

    2007-12-01

    Water and coral mucus samples were collected from throughout the Florida Keys National Marine Sanctuary and the Dry Tortugas for three years and were analyzed for human enteric viruses (enteroviruses, noroviruses, hepatitis A virus and adenoviruses) as conservative markers of human sewage using molecular methods. Of the 100 coral and water samples collected, 40 contained genetic material from one or more human enteric viruses. DNA-based adenoviruses were detected widely, in 37.8% of samples and at 91% of stations, including 'pristine' reefs in the Dry Tortugas; however, the detection rate was < or =12% for the RNA-based enteroviruses and noroviruses (hepatitis A virus was never detected). The disparity between the prevalence of RNA- and DNA-based viruses suggests the need for additional work to determine the utility of adenovirus as marker of human sewage.

  9. Analysis of multiple enteric viral targets as sewage markers in coral reefs

    USGS Publications Warehouse

    Lipp, Erin K.; Futch, J. Carrie; Griffin, Dale W.

    2007-01-01

    Water and coral mucus samples were collected from throughout the Florida Keys National Marine Sanctuary and the Dry Tortugas for three years and were analyzed for human enteric viruses (enteroviruses, noroviruses, hepatitis A virus and adenoviruses) as conservative markers of human sewage using molecular methods. Of the 100 coral and water samples collected, 40 contained genetic material from one or more human enteric viruses. DNA-based adenoviruses were detected widely, in 37.8% of samples and at 91% of stations, including ‘pristine’ reefs in the Dry Tortugas; however, the detection rate was ⩽12% for the RNA-based enteroviruses and noroviruses (hepatitis A virus was never detected). The disparity between the prevalence of RNA- and DNA-based viruses suggests the need for additional work to determine the utility of adenovirus as marker of human sewage.

  10. Comparative proteogenomics: Combining mass spectrometry and comparative genomics to analyze multiple genomes

    PubMed Central

    Gupta, Nitin; Benhamida, Jamal; Bhargava, Vipul; Goodman, Daniel; Kain, Elisabeth; Kerman, Ian; Nguyen, Ngan; Ollikainen, Noah; Rodriguez, Jesse; Wang, Jian; Lipton, Mary S.; Romine, Margaret; Bafna, Vineet; Smith, Richard D.; Pevzner, Pavel A.

    2008-01-01

    Recent proliferation of low-cost DNA sequencing techniques will soon lead to an explosive growth in the number of sequenced genomes and will turn manual annotations into a luxury. Mass spectrometry recently emerged as a valuable technique for proteogenomic annotations that improves on the state-of-the-art in predicting genes and other features. However, previous proteogenomic approaches were limited to a single genome and did not take advantage of analyzing mass spectrometry data from multiple genomes at once. We show that such a comparative proteogenomics approach (like comparative genomics) allows one to address the problems that remained beyond the reach of the traditional “single proteome” approach in mass spectrometry. In particular, we show how comparative proteogenomics addresses the notoriously difficult problem of “one-hit-wonders” in proteomics, improves on the existing gene prediction tools in genomics, and allows identification of rare post-translational modifications. We therefore argue that complementing DNA sequencing projects by comparative proteogenomics projects can be a viable approach to improve both genomic and proteomic annotations. PMID:18426904

  11. Comparative proteogenomics: combining mass spectrometry and comparative genomics to analyze multiple genomes.

    PubMed

    Gupta, Nitin; Benhamida, Jamal; Bhargava, Vipul; Goodman, Daniel; Kain, Elisabeth; Kerman, Ian; Nguyen, Ngan; Ollikainen, Noah; Rodriguez, Jesse; Wang, Jian; Lipton, Mary S; Romine, Margaret; Bafna, Vineet; Smith, Richard D; Pevzner, Pavel A

    2008-07-01

    Recent proliferation of low-cost DNA sequencing techniques will soon lead to an explosive growth in the number of sequenced genomes and will turn manual annotations into a luxury. Mass spectrometry recently emerged as a valuable technique for proteogenomic annotations that improves on the state-of-the-art in predicting genes and other features. However, previous proteogenomic approaches were limited to a single genome and did not take advantage of analyzing mass spectrometry data from multiple genomes at once. We show that such a comparative proteogenomics approach (like comparative genomics) allows one to address the problems that remained beyond the reach of the traditional "single proteome" approach in mass spectrometry. In particular, we show how comparative proteogenomics addresses the notoriously difficult problem of "one-hit-wonders" in proteomics, improves on the existing gene prediction tools in genomics, and allows identification of rare post-translational modifications. We therefore argue that complementing DNA sequencing projects by comparative proteogenomics projects can be a viable approach to improve both genomic and proteomic annotations.

  12. Portable simultaneous multiple analyte whole-blood analyzer for point-of-care testing.

    PubMed

    Schembri, C T; Ostoich, V; Lingane, P J; Burd, T L; Buhl, S N

    1992-09-01

    We describe a portable clinical chemistry analyzer for point-of-care measurements of multiple analytes in less than 10 min from approximately 40 microL of whole blood (fingerstick or venous). Whole blood is applied directly to a 7.9-cm-diameter, single-use plastic rotor containing liquid diluent and greater than or equal to 4-12 tests in the form of 1- to 2-mm-diameter dry reagent beads. The reagent/rotor is immediately placed in a portable instrument along with a ticket/label results card. As the instrument spins the rotor, capillary and rotational forces process the blood into diluted plasma, distribute the patient's diluted sample to cuvettes containing the reagent beads, and mix the diluted sample with the reagents. The instrument monitors the chemical reactions optically at nine wavelengths; sample volume and temperature are also measured optically. The calibration data for each reagent are read from a bar code on the periphery of each rotor. The instrument processes all the measurements to calculate, store, print, and communicate the results. Each reagent/rotor contains an enzymatic control that must be within a defined range before the results from that analysis are reported.

  13. Markers of bone metabolism in multiple myeloma patients switched from zoledronic acid to denosumab.

    PubMed

    Tatekoshi, Ayumi; Sato, Tsutomu; Ibata, Soushi; Hashimoto, Akari; Kamihara, Yusuke; Horiguchi, Hiroto; Ono, Kaoru; Takada, Kohichi; Iyama, Satoshi; Takimoto, Rishu; Kobune, Masayoshi; Kato, Junji

    2014-11-01

    To date, intravenous drip infusion of zoledronic acid (ZA) has mainly been used for the treatment and prevention of skeletal-related events (SRE) in patients with multiple myeloma (MM). Recently, denosumab, a fully humanized monoclonal antibody against receptor activator of nuclear factor-κB ligand (RANKL), has also become available for the same purpose, but little is known about the impact of switching from ZA to denosumab. Herein, we present a retrospective study on bone metabolic markers in 10 MM patients initially treated with ZA and then switched to denosumab. Consequently, the levels of bone resorption markers, tartrate-resistant acid phosphatase 5b (TRACP-5b) and serum type-I collagen crosslinked N-telopeptide (sNTX), significantly decreased after denosumab treatment, while the levels of bone formation markers, osteocalcin (OC) and bone-specific alkaline phosphatase (BAP), showed no apparent changes. No patient developed severe hypocalcemia with denosumab treatment. In one patient not given chemotherapy, the M-protein level increased after switching from ZA to denosumab and plateaued when ZA was restarted. Based on this finding, we anticipate that switching from ZA to denosumab would exert a stronger suppressive effect on osteoclasts, but the anti-myeloma activity of ZA must be taken into consideration.

  14. Cholesterol and markers of cholesterol turnover in multiple sclerosis: relationship with disease outcomes.

    PubMed

    Zhornitsky, Simon; McKay, Kyla A; Metz, Luanne M; Teunissen, Charlotte E; Rangachari, Manu

    2016-01-01

    Multiple sclerosis (MS) is a chronic central nervous system disease that is associated with progressive loss of myelin and subsequent axonal degeneration. Cholesterol is an essential component of mammalian cellular and myelin membranes. In this systematic review, we examined the relationship between levels of cholesterol and markers of cholesterol turnover in circulation and/or cerebrospinal fluid (CSF) and disease outcomes in adults with clinically isolated syndrome (CIS) or confirmed MS. Studies suggest that elevated levels of circulating low density lipoprotein cholesterol (LDL), total cholesterol, and particularly, apolipoprotein B and oxidized LDL are associated with adverse clinical and MRI outcomes in MS. These relationships were observed as early as CIS. The studies also suggest that oxysterols, cholesterol precursors, and apolipoprotein E may be markers of specific disease processes in MS, but more research is required to elucidate these processes and relationships. Taken together, the data indicate that cholesterol and markers of cholesterol turnover have potential to be used clinically as biomarkers of disease activity and may even be implicated in the pathogenesis of MS.

  15. Genetic connectivity in the broadcast-spawning coral Acropora digitifera analyzed by microsatellite markers on the Sekisei Reef, southwestern Japan.

    PubMed

    Nakajima, Yuichi; Nishikawa, Akira; Isomura, Naoko; Iguchi, Akira; Sakai, Kazuhiko

    2009-03-01

    Worldwide decline has been observed in coral populations due to environmental changes at both regional and global levels. Since corals have a typical metapopulation structure, the recovery of severely disturbed local populations depends on larval recruitment from outside the disturbed region. Therefore, the connectivity among local populations may play a key role in the disturbance/ recovery dynamics of coral populations. On the basis of the simulation of surface currents, derived from ocean currents, we hypothesized that the genetic connectivity of coral populations is weak between the northern and southern regions of Sekisei Reef, Japan. To test this hypothesis, the connectivity of the population of the broadcast-spawning coral Acropora digitifera, one of the dominant corals in the Sekisei Reef, was analyzed at six sampling sites that were 5-25 km apart by using six microsatellite markers. The degree of genetic differentiation of A. digitifera was very low among all the sites (F(ST) from -0.006 to 0.015), and no evidence was found in support of our hypothesis. The relative lack of genetic differentiation of A. digitifera among the sites may be attributable to the large effect of wind-driven surface currents, which highly vary on an annual basis, on coral larvae or to the time gap between simulation based on ocean current patterns and accumulation of genetic differences. Considering the pattern of the genetic connectivity of A. digitifera in the Sekisei Reef, the sites that are located within less-disturbed areas may act as larval sources and should, therefore, be preserved.

  16. Real-time segmentation of multiple implanted cylindrical liver markers in kilovoltage and megavoltage x-ray images

    NASA Astrophysics Data System (ADS)

    Fledelius, W.; Worm, E.; Høyer, M.; Grau, C.; Poulsen, P. R.

    2014-06-01

    Gold markers implanted in or near a tumor can be used as x-ray visible landmarks for image based tumor localization. The aim of this study was to develop and demonstrate fast and reliable real-time segmentation of multiple liver tumor markers in intra-treatment kV and MV images and in cone-beam CT (CBCT) projections, for real-time motion management. Thirteen patients treated with conformal stereotactic body radiation therapy in three fractions had 2-3 cylindrical gold markers implanted in the liver prior to treatment. At each fraction, the projection images of a pre-treatment CBCT scan were used for automatic generation of a 3D marker model that consisted of the size, orientation, and estimated 3D trajectory of each marker during the CBCT scan. The 3D marker model was used for real-time template based segmentation in subsequent x-ray images by projecting each marker's 3D shape and likely 3D motion range onto the imager plane. The segmentation was performed in intra-treatment kV images (526 marker traces, 92 097 marker projections) and MV images (88 marker traces, 22 382 marker projections), and in post-treatment CBCT projections (42 CBCT scans, 71 381 marker projections). 227 kV marker traces with low mean contrast-to-noise ratio were excluded as markers were not visible due to MV scatter. Online segmentation times measured for a limited dataset were used for estimating real-time segmentation times for all images. The percentage of detected markers was 94.8% (kV), 96.1% (MV), and 98.6% (CBCT). For the detected markers, the real-time segmentation was erroneous in 0.2-0.31% of the cases. The mean segmentation time per marker was 5.6 ms [2.1-12 ms] (kV), 5.5 ms [1.6-13 ms] (MV), and 6.5 ms [1.8-15 ms] (CBCT). Fast and reliable real-time segmentation of multiple liver tumor markers in intra-treatment kV and MV images and in CBCT projections was demonstrated for a large dataset.

  17. 21 CFR 862.2150 - Continuous flow sequential multiple chemistry analyzer for clinical use.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Continuous flow sequential multiple chemistry..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Laboratory Instruments § 862.2150 Continuous flow sequential multiple chemistry...

  18. 21 CFR 862.2150 - Continuous flow sequential multiple chemistry analyzer for clinical use.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Continuous flow sequential multiple chemistry..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Laboratory Instruments § 862.2150 Continuous flow sequential multiple chemistry...

  19. 21 CFR 862.2150 - Continuous flow sequential multiple chemistry analyzer for clinical use.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Continuous flow sequential multiple chemistry..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Laboratory Instruments § 862.2150 Continuous flow sequential multiple chemistry...

  20. 21 CFR 862.2150 - Continuous flow sequential multiple chemistry analyzer for clinical use.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Continuous flow sequential multiple chemistry..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Laboratory Instruments § 862.2150 Continuous flow sequential multiple chemistry...

  1. 21 CFR 862.2150 - Continuous flow sequential multiple chemistry analyzer for clinical use.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Continuous flow sequential multiple chemistry..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Laboratory Instruments § 862.2150 Continuous flow sequential multiple chemistry...

  2. Development of microsatellite markers from the transcriptome of Erysiphe necator for analyzing population structure in North America and Europe

    USDA-ARS?s Scientific Manuscript database

    We used transcriptome sequences of the grape powdery mildew fungus, Erysiphe necator, to develop microsatellite markers (EST-SSRs) to study its relatively unexplored population structure in its center of diversity in eastern North America. Screening the transcriptome sequences revealed 116 contigs w...

  3. Fingolimod modulates multiple neuroinflammatory markers in a mouse model of Alzheimer’s disease

    PubMed Central

    Aytan, Nurgul; Choi, Ji-Kyung; Carreras, Isabel; Brinkmann, Volker; Kowall, Neil W.; Jenkins, Bruce G.; Dedeoglu, Alpaslan

    2016-01-01

    Sphingosine 1-phosphate (SP1) receptors may be attractive targets for modulation of inflammatory processes in neurodegenerative diseases. Recently fingolimod, a functional S1P1 receptor antagonist, was introduced for treatment of multiple sclerosis. We postulated that anti-inflammatory mechanisms of fingolimod might also be protective in Alzheimer’s disease (AD). Therefore, we treated a mouse model of AD, the 5xFAD model, with two doses of fingolimod (1 and 5 mg/kg/day) and measured the response of numerous markers of Aβ pathology as well as inflammatory markers and neurochemistry using biochemical, immunohistochemistry and high resolution magic angle spinning magnetic resonance spectroscopy (MRS). In mice at 3 months of age, we found that fingolimod decreased plaque density as well as soluble plus insoluble Aβ measured by ELISA. Fingolimod also decreased GFAP staining and the number of activated microglia. Taurine has been demonstrated to play a role as an endogenous anti-inflammatory molecule. Taurine levels, measured using MRS, showed a very strong inverse correlation with GFAP levels and ELISA measurements of Aβ, but not with plaque density or activated microglia levels. MRS also showed an effect of fingolimod on glutamate levels. Fingolimod at 1 mg/kg/day provided better neuroprotection than 5 mg/kg/day. Together, these data suggest a potential therapeutic role for fingolimod in AD. PMID:27117087

  4. Comparison of gSSR and EST-SSR markers for analyzing genetic variability among tomato cultivars (Solanum lycopersicum L.).

    PubMed

    Zhou, R; Wu, Z; Jiang, F L; Liang, M

    2015-10-27

    In order to study genetic variability and develop better strategies for the utilization of 48 tomato cultivars from America, China, the Netherlands, and Portugal, genomic simple sequence repeat (gSSR) and EST-derived SSR (EST-SSR) markers were applied. In all, 15 of 82 gSSR and 18 of 115 EST-SSR markers showed polymorphic loci. There were 995 and 2072 clear fragments amplified by polymorphic gSSR and EST-SSR markers, respectively. The total and average number of alleles detected by EST-SSRs (75, 4.2) was more than gSSRs (54, 3.6) as a result of some multi-locus EST-SSRs. A lower polymorphism information content value was found in gSSRs (0.529) compared to EST-SSRs (0.620). Similarity coefficient matrixes of the 48 tomato cultivars were established based on the gSSRs and EST-SSRs, and UPGMA dendrograms were constructed from the gSSRs and EST-SSRs similarity coefficient matrixes. A high similarity was observed between the gSSRs and EST-SSRs dendrograms. Genetic variability of four tomato populations from different countries showed that the observed number of alleles and Nei's genetic diversity were highest in the American population, and the effective number of alleles was highest in the Dutch population. The estimated genetic structure showed some tomato cultivars from different countries shared a common genetic background, which might be related to gene flow. It was inferred that both gSSR and EST-SSR markers were effective to assess genetic variability of tomato cultivars, and the combination of both markers could be more effective for genetic diversity analysis in tomato.

  5. A discrimination index for selecting markers of tumor growth dynamic across multiple cancer studies with a cure fraction.

    PubMed

    Rouam, Sigrid; Broët, Philippe

    2013-08-01

    To identify genomic markers with consistent effect on tumor dynamics across multiple cancer series, discrimination indices based on proportional hazards models can be used since they do not depend heavily on the sample size. However, the underlying assumption of proportionality of the hazards does not always hold, especially when the studied population is a mixture of cured and uncured patients, like in early-stage cancers. We propose a novel index that quantifies the capability of a genomic marker to separate uncured patients, according to their time-to-event outcomes. It allows to identify genomic markers characterizing tumor growth dynamic across multiple studies. Simulation results show that our index performs better than classical indices based on the Cox model. It is neither affected by the sample size nor the cure rate fraction. In a cross-study of early-stage breast cancers, the index allows to select genomic markers with a potential consistent effect on tumor growth dynamics.

  6. Accelerometry and Its Association With Objective Markers of Walking Limitations in Ambulatory Adults With Multiple Sclerosis

    PubMed Central

    Motl, Robert W.; Dlugonski, Deirdre; Suh, Yoojin; Weikert, Madeline; Fernhall, Bo; Goldman, Myla

    2011-01-01

    Objective To validate accelerometry based on its correlations with 6-minute walk distance (6MWD) and oxygen cost of walking as objective markers of walking limitations in multiple sclerosis (MS). Design Cross-sectional. Setting Laboratory and general community. Participants Ambulatory participants with MS (N=26) who resided in the local community. Interventions Not applicable. Main Outcome Measures Patient Determined Disease Steps (PDDS) scale and Multiple Sclerosis Walking Scale-12 (MSWS-12); 6-minute walk test while wearing a portable metabolic unit for measuring the 6MWD and oxygen cost of walking; accelerometer during the waking hours of a 7-day period. Results The average of total daily movement counts from the accelerometer correlated significantly and strongly with MSWS-12 scores (ρ−.681, P=.001), PDDS scores (ρ−.609, P=.001), 6MWD (ρ.519, P=.003), and oxygen cost of walking (ρ−.541, P=.002). Conclusions We provide evidence that further supports the validity of accelerometry as a measure of walking limitations in ambulatory persons with MS. PMID:21112438

  7. Serum YKL-40: a new independent prognostic marker for skeletal complications in patients with multiple myeloma.

    PubMed

    Mylin, Anne K; Abildgaard, Niels; Johansen, Julia S; Heickendorff, Lene; Kreiner, Svend; Waage, Anders; Turesson, Ingemar; Gimsing, Peter

    2015-01-01

    In a time of increasing treatment options for multiple myeloma bone disease, risk factors predicting progression need to be elucidated. This study investigated the value of serum YKL-40, previously shown to be associated with radiographic progression of bone destruction, as a predictor for time to clinical progression, i.e. skeletal-related events (SREs), in 230 newly diagnosed patients with multiple myeloma receiving intravenous bisphosphonates. Serum concentrations of YKL-40 and biochemical bone markers (CTX-MMP, CTX-I, PINP) were measured at diagnosis. Patients were evaluated every third month for SRE and at 9 and 24 months for radiographic progression. Elevated serum YKL-40 was seen in 47% of patients and associated with high-risk disease (International Staging System stage III; p < 0.001), increased bone resorption (serum CTX/MMP; p < 0.001) and early radiographic progression at 9 months (p = 0.01). Serum YKL-40 together with serum CTX-MMP/PINP ratio and World Health Organization status were independent predictors of time to first SRE.

  8. Uncovering Cryptic Glycan Markers in Multiple Sclerosis (MS) and Experimental Autoimmune Encephalomyelitis (EAE)

    PubMed Central

    Wang, Denong; Bhat, Roopa; Sobel, Raymond A.; Huang, Wei; Wang, Lai-Xi; Olsson, Tomas; Steinman, Lawrence

    2014-01-01

    Strategy, Management and Health PolicyEnabling Technology, Genomics, ProteomicsPreclinical ResearchPreclinical Development Toxicology, Formulation Drug Delivery, PharmacokineticsClinical Development Phases I-III Regulatory, Quality, ManufacturingPostmarketing Phase IV Using an integrated antigen microarray approach, we observed epitope-spreading of autoantibody responses to a variety of antigenic structures in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) and in the serum of mice with experimental autoimmune encephalomyelitis (EAE). These included previously described protein- and lipid-based antigenic targets and newly discovered autoimmunogenic sugar moieties, notably, autoantibodies specific for the oligomannoses in both MS patient CSF and the sera of mice with EAE. These glycans are often masked by other sugar moieties and belong to a class of cryptic autoantigens. We further determined that these targets are highly expressed on multiple cell types in MS and EAE lesions. Co-immunization of SJL/J mice with a Man9-KLH conjugate at the time of EAE induction elicited highly significant levels of anti-Man9-cluster autoantibodies. Nevertheless, this anti-glycan autoantibody response was associated with a significantly reduced clinical severity of EAE. The potential of these cryptic glycan markers and targeting antibodies for diagnostic and therapeutic interventions of neurological disorders has yet to be explored. PMID:24648292

  9. What Is Wrong with ANOVA and Multiple Regression? Analyzing Sentence Reading Times with Hierarchical Linear Models

    ERIC Educational Resources Information Center

    Richter, Tobias

    2006-01-01

    Most reading time studies using naturalistic texts yield data sets characterized by a multilevel structure: Sentences (sentence level) are nested within persons (person level). In contrast to analysis of variance and multiple regression techniques, hierarchical linear models take the multilevel structure of reading time data into account. They…

  10. Explorative Function in Williams Syndrome Analyzed through a Large-Scale Task with Multiple Rewards

    ERIC Educational Resources Information Center

    Foti, F.; Petrosini, L.; Cutuli, D.; Menghini, D.; Chiarotti, F.; Vicari, S.; Mandolesi, L.

    2011-01-01

    This study aimed to evaluate spatial function in subjects with Williams syndrome (WS) by using a large-scale task with multiple rewards and comparing the spatial abilities of WS subjects with those of mental age-matched control children. In the present spatial task, WS participants had to explore an open space to search nine rewards placed in…

  11. Explorative Function in Williams Syndrome Analyzed through a Large-Scale Task with Multiple Rewards

    ERIC Educational Resources Information Center

    Foti, F.; Petrosini, L.; Cutuli, D.; Menghini, D.; Chiarotti, F.; Vicari, S.; Mandolesi, L.

    2011-01-01

    This study aimed to evaluate spatial function in subjects with Williams syndrome (WS) by using a large-scale task with multiple rewards and comparing the spatial abilities of WS subjects with those of mental age-matched control children. In the present spatial task, WS participants had to explore an open space to search nine rewards placed in…

  12. Pharmacogenetics of glatiramer acetate therapy for multiple sclerosis reveals drug-response markers.

    PubMed

    Grossman, Iris; Avidan, Nili; Singer, Clara; Goldstaub, Dan; Hayardeny, Liat; Eyal, Eli; Ben-Asher, Edna; Paperna, Tamar; Pe'er, Itsik; Lancet, Doron; Beckmann, Jacques S; Miller, Ariel

    2007-08-01

    Genetic-based optimization of treatment prescription is becoming a central research focus in the management of chronic diseases, such as multiple sclerosis, which incur a prolonged drug-regimen adjustment. This study was aimed to identify genetic markers that can predict response to glatiramer acetate (Copaxone) immunotherapy for relapsing multiple sclerosis. For this purpose, we genotyped fractional cohorts of two glatiramer acetate clinical trials for HLA-DRB1*1501 and 61 single nucleotide polymorphisms within a total of 27 candidate genes. Statistical analyses included single nucleotide polymorphism-by-single nucleotide polymorphism and haplotype tests of drug-by-genotype effects in drug-treated versus placebo-treated groups. We report the detection of a statistically significant association between glatiramer acetate response and a single nucleotide polymorphism in a T-cell receptor beta (TRB@) variant replicated in the two independent cohorts (odds ratio=6.85). Findings in the Cathepsin S (CTSS) gene (P=0.049 corrected for all single nucleotide polymorphisms and definitions tested, odds ratio=11.59) in one of the cohorts indicate a possible association that needs to be further investigated. Additionally, we recorded nominally significant associations of response with five other genes, MBP, CD86, FAS, IL1R1 and IL12RB2, which are likely to be involved in glatiramer acetate's mode-of-action, both directly and indirectly. Each of these association signals in and of itself is consistent with the no-association null-hypothesis, but the number of detected associations is surprising vis-à-vis chance expectation. Moreover, the restriction of these associations to the glatiramer acetate-treated group, rather than the placebo group, clearly demonstrates drug-specific genetic effects. These findings provide additional progress toward development of pharmacogenetics-based personalized treatment for multiple sclerosis.

  13. HAL: a hierarchical format for storing and analyzing multiple genome alignments.

    PubMed

    Hickey, Glenn; Paten, Benedict; Earl, Dent; Zerbino, Daniel; Haussler, David

    2013-05-15

    Large multiple genome alignments and inferred ancestral genomes are ideal resources for comparative studies of molecular evolution, and advances in sequencing and computing technology are making them increasingly obtainable. These structures can provide a rich understanding of the genetic relationships between all subsets of species they contain. Current formats for storing genomic alignments, such as XMFA and MAF, are all indexed or ordered using a single reference genome, however, which limits the information that can be queried with respect to other species and clades. This loss of information grows with the number of species under comparison, as well as their phylogenetic distance. We present HAL, a compressed, graph-based hierarchical alignment format for storing multiple genome alignments and ancestral reconstructions. HAL graphs are indexed on all genomes they contain. Furthermore, they are organized phylogenetically, which allows for modular and parallel access to arbitrary subclades without fragmentation because of rearrangements that have occurred in other lineages. HAL graphs can be created or read with a comprehensive C++ API. A set of tools is also provided to perform basic operations, such as importing and exporting data, identifying mutations and coordinate mapping (liftover). All documentation and source code for the HAL API and tools are freely available at http://github.com/glennhickey/hal. hickey@soe.ucsc.edu or haussler@soe.ucsc.edu Supplementary data are available at Bioinformatics online.

  14. Effects of ivermectin on Danio rerio: a multiple endpoint approach: behaviour, weight and subcellular markers.

    PubMed

    Domingues, I; Oliveira, R; Soares, A M V M; Amorim, M J B

    2016-04-01

    Ivermectin (IVM) is a broad acting antihelmintic used in various veterinary pharmaceuticals. It has been shown that IVM enters the aquatic compartment and adversely affects organisms including fish. This study is based on the hypothesis that long term exposure to IVM affects fish and thus, the main objective was to assess the chronic effects of 0.25 and 25 µg IVM/L to zebrafish using multiple endpoints representative of several levels of biological organization: weight, behaviour (swimming and feeding) and subcellular markers including biomarkers for oestrogenicity (vitellogenin-VTG), oxidative stress (catalase-CAT and glutathione-S-transferase-GST) and neurotransmission (cholinesterase-ChE). Concentrations as low as 0.25 µg IVM/L disrupted the swimming behaviour, causing fish to spend more time at the bottom of aquaria. Such reduction of the swimming performance affected the feeding ability which is likely responsible for the weight loss. The effects on weight were gender differentiated, being more pronounced in males (0.25 µg IVM/L) than in females (25 µg IVM/L). Fish exposed to 25 µg/L exhibited darker coloration and mild curvature of the spine. No effects on VTG and AChE were observed, but a reduction on CAT and GST levels was observed in fish exposed to 25 µg IVM/L, although these alterations probably only reflect the general condition of the fish which was significantly compromised at this concentration. Despite that predicted environmental concentrations of IVM are below 0.25 µg/L, the behavioural effects may be translated into important ecological impacts, e.g. at predator-prey interactions where fish competitive advantage can be decreased. Future work should address the link between behaviour disruption and population fitness. The current study was based on a one experiment and multiple endpoint (anchored) approach, allowing the results to be integrated and linked towards a mechanistic understanding.

  15. Analyzing Statistical Mediation with Multiple Informants: A New Approach with an Application in Clinical Psychology

    PubMed Central

    Papa, Lesther A.; Litson, Kaylee; Lockhart, Ginger; Chassin, Laurie; Geiser, Christian

    2015-01-01

    Testing mediation models is critical for identifying potential variables that need to be targeted to effectively change one or more outcome variables. In addition, it is now common practice for clinicians to use multiple informant (MI) data in studies of statistical mediation. By coupling the use of MI data with statistical mediation analysis, clinical researchers can combine the benefits of both techniques. Integrating the information from MIs into a statistical mediation model creates various methodological and practical challenges. The authors review prior methodological approaches to MI mediation analysis in clinical research and propose a new latent variable approach that overcomes some limitations of prior approaches. An application of the new approach to mother, father, and child reports of impulsivity, frustration tolerance, and externalizing problems (N = 454) is presented. The results showed that frustration tolerance mediated the relationship between impulsivity and externalizing problems. The new approach allows for a more comprehensive and effective use of MI data when testing mediation models. PMID:26617536

  16. Analyzing multiple cross-sectional samples with application to hospitalization time after surgeries.

    PubMed

    Mandel, Micha

    2015-11-20

    Repeated cross-sectional sampling results in multiple biased samples with possibly different weight functions. The standard non-parametric maximum likelihood estimator for the lifetime distribution of interest solves a set of nonlinear equations, and its variance has a very complicated form. We suggest a simple closed-form estimator for the case where entrances to the population of interest follow a Poisson model. The variance of the estimator and confidence intervals are easily calculated. Our motivating example concerns a series of cross-sectional surveys conducted in Israeli hospitals. We discuss the bias mechanism in our data and suggest a simple design plan that provides valid estimators even when the weight functions are unknown. The new method is applied to estimate the distribution of hospitalization time after bowel and hernia surgeries.

  17. Balancing precision and risk: should multiple detection methods be analyzed separately in N-mixture models?

    USGS Publications Warehouse

    Graves, Tabitha A.; Royle, J. Andrew; Kendall, Katherine C.; Beier, Paul; Stetz, Jeffrey B.; Macleod, Amy C.

    2012-01-01

    Using multiple detection methods can increase the number, kind, and distribution of individuals sampled, which may increase accuracy and precision and reduce cost of population abundance estimates. However, when variables influencing abundance are of interest, if individuals detected via different methods are influenced by the landscape differently, separate analysis of multiple detection methods may be more appropriate. We evaluated the effects of combining two detection methods on the identification of variables important to local abundance using detections of grizzly bears with hair traps (systematic) and bear rubs (opportunistic). We used hierarchical abundance models (N-mixture models) with separate model components for each detection method. If both methods sample the same population, the use of either data set alone should (1) lead to the selection of the same variables as important and (2) provide similar estimates of relative local abundance. We hypothesized that the inclusion of 2 detection methods versus either method alone should (3) yield more support for variables identified in single method analyses (i.e. fewer variables and models with greater weight), and (4) improve precision of covariate estimates for variables selected in both separate and combined analyses because sample size is larger. As expected, joint analysis of both methods increased precision as well as certainty in variable and model selection. However, the single-method analyses identified different variables and the resulting predicted abundances had different spatial distributions. We recommend comparing single-method and jointly modeled results to identify the presence of individual heterogeneity between detection methods in N-mixture models, along with consideration of detection probabilities, correlations among variables, and tolerance to risk of failing to identify variables important to a subset of the population. The benefits of increased precision should be weighed against

  18. Multiple markers of hypercoagulation in patients with history of venous thromboembolic disease.

    PubMed

    Bern, Murray; McCarthy, Nancy

    2013-01-01

    Markers for hypercoagulation can be used to explain why some patients may have had thromboembolic disease (TED). This information may then be applied to estimate risk for additional TED that may afflict these patients following subsequent surgeries. This investigation was to determine the frequency of hypercoagulation parameters among patients having had TED, and how frequently these occur in multiples. Consulting hematologists were asked to comment upon potential risk for recurrent TED that may be associated with additional surgeries. The consulting hematologist determined which laboratory tests were to be ordered for each patient. This retrospective study probed the hospital computer logs for patients having had homocysteine, protein C, factor V Leiden or anticardiolipin antibodies measured during a 6-year period. The laboratory records for patients having had any one of these tests were then examined further for any additional hypercoagulation laboratory studies performed. Five hundred and twenty patients were identified in this survey. Abnormal diagnostic results were found for 293 (56.3%) of these patients. Two or more abnormalities (up to 5) were found for 103 (35.6%) of these patients. Laboratory explanations for TED may be found in a large proportion of patients with TED. It is not uncommon to find more than one abnormality among these patients. This information may be used in advising patients and their physicians as to the risks of additional TED following future surgical procedures and can be the basis for recommending life style changes.

  19. Relationship between pulmonary and systemic markers of exposure to multiple types of welding particulate matter.

    PubMed

    Erdely, Aaron; Salmen-Muniz, Rebecca; Liston, Angie; Hulderman, Tracy; Zeidler-Erdely, Patti C; Antonini, James M; Simeonova, Petia P

    2011-09-05

    Welding results in a unique and complex occupational exposure. Recent epidemiological studies have shown an increased risk of cardiovascular disease following welding fume exposure. In this study, we compared the induction of pulmonary and systemic inflammation following exposure to multiple types of welding fumes. Mice were exposed to 340μg of manual metal arc stainless steel (MMA-SS), gas metal arc-SS (GMA-SS) or GMA-mild steel (GMA-MS) by pharyngeal aspiration. Mice were sacrificed at 4 and 24h post-exposure to evaluate various parameters of pulmonary and systemic inflammation. Alterations in pulmonary gene expression by a custom designed TaqMan array showed minimal differences between the fumes at 4h. Conversely at 24h, gene expression changes were further increased by SS but not GMA-MS exposure. These findings were associated with the surrogate marker of systemic inflammation, liver acute phase gene induction. Interestingly, stress response genes in cardiovascular tissues were only increased following MMA-SS exposure. These effects were related to the initial level of pulmonary cytotoxicity, as measured by lactate dehydrogenase activity, which was greatest following MMA-SS exposure. In conclusion, varying types of welding fumes elicit quantitatively different systemic inflammatory and/or stress responses. Published by Elsevier Ireland Ltd.

  20. [Cutaneous lesion associated with multiple endocrine neoplasms type 2A (Sipple's syndrome). An early clinical marker].

    PubMed

    Chabre, O; Labat-Moleur, F; Berthod, F; Tarel, V; Stoebner, P; Sobol, H; Bachelot, I

    1992-02-22

    We report the association of a cutaneous lesion with multiple endocrine neoplasia type 2A (MEN 2A) in three patients from a French family. These lesions are very similar to those previously described in an Italian and an American MEN 2A family and called cutaneous lichen amyloidosis. In all three families the patients presented with a pruritic and pigmented cutaneous lesion localized unilaterally on the upper back. However, in the French family the patients also complained of paroxysmal pain in the same area, in which we could elicit a touch hypoesthesia and pain hyperesthesia. Such an association of cutaneous and neurological features in the upper back is known as Notalgia Paresthetica (NP). NP is believed to represent a neuropathy of the posterior dorsal nerve rami. Unlike the two previously reported families, the histological, immunohistochemical and ultrastructural analysis of the skin biopsies of the French patients did not show any amyloid material. This suggests that the presence of amyloid may not be a constant feature of the cutaneous lesions associated with MEN 2A. We consider these lesions as a form of dorsal neuropathy rather than a cutaneous lichen amyloidosis. Whatever their origin, these cutaneous lesion usually precede the appearance of the neoplastic lesions of MEN 2A. They may act as an early clinical marker that must be searched for in each subject at risk for MEN 2A. In addition, all patients presenting with NP should be screened for MEN 2A.

  1. MSRV pol sequence copy number as a potential marker of multiple sclerosis.

    PubMed

    Zawada, Mariola; Liwień, Izabela; Pernak, Monika; Januszkiewicz-Lewandowska, Danuta; Nowicka-Kujawska, Karina; Rembowska, Jolanta; Lewandowski, Krzysztof; Hertmanowska, Hanna; Wender, Mieczysław; Nowak, Jerzy

    2003-01-01

    Multiple sclerosis (MS) is a neurological disease in which demyelination in the brain and spinal cord is observed. The causal influence of bacterial/viral infections and genetic/immune factors in the etiology of multiple sclerosis is suggested. Multiple sclerosis-related retrovirus (MSRV) is one of the potential agents, which can lead to development of the disease. The aim of cytogenetic studies was assessment of MSRV pol sequence copy number in patients with MS compared to normal individuals. Cytogenetic slides with interphase nuclei and extended chromatin fibers were prepared from peripheral blood of 16 patients with MS and 10 healthy individuals. Fluorescence in situ hybridization (FISH) with biotinylated product of polymerase chain reaction was used in order to analyze MSRV pol sequence copy number in the examined material. Detection of MSRV pol probe was carried out by immunological reaction with avidin-fluorescein and biotinylated anti-avidin. MSRV pol sequence copy number was significantly greater in MS patients than in normal individuals. Using FISH technique to extended chromatin fibers, it was observed that MSRV pol exists as tandem repeats on various chromosomes. The increased number of MSRV pol sequence has been found on chromatin fibers of MS patients as compared to healthy controls.

  2. Comparative proteogenomics: combining mass spectrometry and comparative genomics to analyze multiple genomes

    SciTech Connect

    Gupta, Nitin; Benhamida, Jamal; Bhargava, Vipul; Goodman, Daniel; Kain , Elisabeth; Kerman, Ian; Nguyen , Ngan; Ollikainen, Noah; Rodriguez, Jesse; Wang, J.; Lipton, Mary S.; Romine, Margaret F.; Bafna, Vineet; Smith, Richard D.; Pevzner, Pavel A.

    2008-07-30

    While bacterial genome annotations have significantly improved in recent years, techniques for bacterial proteome annotation (including post-translational chemical modifications, signal peptides, proteolytic events, etc.) are still in their infancy. At the same time, the number of sequenced bacterial genomes is rising sharply, far outpacing our ability to validate the predicted genes, let alone annotate bacterial proteomes. In this study, we use tandem mass spectrometry (MS/MS) to annotate the proteome of Shewanella oneidensis MR-1, an important microbe for bioremediation. In particular, we provide the first comprehensive map of post-translational modifications in a bacterial genome, including a large number of chemical modifications, signal peptide cleavages and cleavage of N-terminal methionine residues. We also detect multiple genes that were missed or assigned incorrect start positions by gene prediction programs and suggest corrections to improve the gene annotation. This study demonstrates that complementing every genome sequencing project by an MS/MS project would significantly improve both genome and proteome annotations for a reasonable cost.

  3. Detecting and Analyzing Multiple Moving Objects in Crowded Environments with Coherent Motion Regions

    SciTech Connect

    Cheriyadat, Anil M.

    2013-01-04

    Understanding the world around us from large-scale video data requires vision systems that can perform automatic interpretation. While human eyes can unconsciously perceive independent objects in crowded scenes and other challenging operating environments, automated systems have difficulty detecting, counting, and understanding their behavior in similar scenes. Computer scientists at ORNL have a developed a technology termed as "Coherent Motion Region Detection" that invloves identifying multiple indepedent moving objects in crowded scenes by aggregating low-level motion cues extracted from moving objects. Humans and other species exploit such low-level motion cues seamlessely to perform perceptual grouping for visual understanding. The algorithm detects and tracks feature points on moving objects resulting in partial trajectories that span coherent 3D region in the space-time volume defined by the video. In the case of multi-object motion, many possible coherent motion regions can be constructed around the set of trajectories. The unique approach in the algorithm is to identify all possible coherent motion regions, then extract a subset of motion regions based on an innovative measure to automatically locate moving objects in crowded environments.The software reports snapshot of the object, count, and derived statistics ( count over time) from input video streams. The software can directly process videos streamed over the internet or directly from a hardware device (camera).

  4. A dynamic factor modeling framework for analyzing multiple groundwater head series simultaneously

    NASA Astrophysics Data System (ADS)

    Berendrecht, W. L.; van Geer, F. C.

    2016-05-01

    In this paper we present an approach in which we combine a dynamic factor model (DFM) and predefined response functions to analyze a set of groundwater head series simultaneously. Each groundwater head series is decomposed into: (a) one or more deterministic components as a response to known driving forces, (b) one or more common dynamic factors, representing spatial patterns not related to any of the input series and (c) one specific dynamic factor for each groundwater head series, describing unique variation for that series. The approach reduces the degrees of freedom for each response function, enables the application to irregular observed data, and exploits the correlation between residual series of a set of groundwater head series. The common dynamic factors may be interpreted as spatial patterns due to e.g. limitations in the model specification or concept, spatially correlated errors in input variables, or driving forces which have not been included in the model. In the latter case the model can be applied in the context of an alarming system, e.g. to monitor regional trends. The specific dynamic factor depicts the variation of a particular groundwater head series that cannot be related to any other time series of the set nor to any input series. Therefore the specific dynamic factor is suitable for analyzing local variations and detecting incidental measurement errors, for example in a quality control procedure. The DFM framework is illustrated with a set of 8 groundwater head series and applied for filling gaps in time series, reconstructing high-frequency data, and detecting outliers.

  5. A novel data mining system points out hidden relationships between immunological markers in multiple sclerosis

    PubMed Central

    2013-01-01

    Background Multiple Sclerosis (MS) is a multi-factorial disease, where a single biomarker unlikely can provide comprehensive information. Moreover, due to the non-linearity of biomarkers, traditional statistic is both unsuitable and underpowered to dissect their relationship. Patients affected with primary (PP=14), secondary (SP=33), benign (BB=26), relapsing-remitting (RR=30) MS, and 42 sex and age matched healthy controls were studied. We performed a depth immune-phenotypic and functional analysis of peripheral blood mononuclear cell (PBMCs) by flow-cytometry. Semantic connectivity maps (AutoCM) were applied to find the natural associations among immunological markers. AutoCM is a special kind of Artificial Neural Network able to find consistent trends and associations among variables. The matrix of connections, visualized through minimum spanning tree, keeps non linear associations among variables and captures connection schemes among clusters. Results Complex immunological relationships were shown to be related to different disease courses. Low CD4IL25+ cells level was strongly related (link strength, ls=0.81) to SP MS. This phenotype was also associated to high CD4ROR+ cells levels (ls=0.56). BB MS was related to high CD4+IL13 cell levels (ls=0.90), as well as to high CD14+IL6 cells percentage (ls=0.80). RR MS was strongly (ls=0.87) related to CD4+IL25 high cell levels, as well indirectly to high percentages of CD4+IL13 cells. In this latter strong (ls=0.92) association could be confirmed the induction activity of the former cells (CD4+IL25) on the latter (CD4+IL13). Another interesting topographic data was the isolation of Th9 cells (CD4IL9) from the main part of the immunological network related to MS, suggesting a possible secondary role of this new described cell phenotype in MS disease. Conclusions This novel application of non-linear mathematical techniques suggests peculiar immunological signatures for different MS phenotypes. Notably, the immune

  6. Method of analyzing multiple sample simultaneously by detecting absorption and systems for use in such a method

    DOEpatents

    Yeung, Edward S.; Gong, Xiaoyi

    2004-09-07

    The present invention provides a method of analyzing multiple samples simultaneously by absorption detection. The method comprises: (i) providing a planar array of multiple containers, each of which contains a sample comprising at least one absorbing species, (ii) irradiating the planar array of multiple containers with a light source and (iii) detecting absorption of light with a detetion means that is in line with the light source at a distance of at leaat about 10 times a cross-sectional distance of a container in the planar array of multiple containers. The absorption of light by a sample indicates the presence of an absorbing species in it. The method can further comprise: (iv) measuring the amount of absorption of light detected in (iii) indicating the amount of the absorbing species in the sample. Also provided by the present invention is a system for use in the abov metho.The system comprises; (i) a light source comrnpising or consisting essentially of at leaat one wavelength of light, the absorption of which is to be detected, (ii) a planar array of multiple containers, and (iii) a detection means that is in line with the light source and is positioned in line with and parallel to the planar array of multiple contiainers at a distance of at least about 10 times a cross-sectional distance of a container.

  7. Analyzing climate variations at multiple timescales can guide Zika virus response measures.

    PubMed

    Muñoz, Ángel G; Thomson, Madeleine C; Goddard, Lisa; Aldighieri, Sylvain

    2016-10-06

    The emergence of Zika virus (ZIKV) in Latin America and the Caribbean in 2014-2016 occurred during a period of severe drought and unusually high temperatures, conditions that have been associated with the 2015-2016 El Niño event, and/or climate change; however, no quantitative assessment has been made to date. Analysis of related flaviviruses transmitted by the same vectors suggests that ZIKV dynamics are sensitive to climate seasonality and longer-term variability and trends. A better understanding of the climate conditions conducive to the 2014-2016 epidemic may permit the development of climate-informed short and long-term strategies for ZIKV prevention and control. Using a novel timescale-decomposition methodology, we demonstrate that the extreme climate anomalies observed in most parts of South America during the current epidemic are not caused exclusively by El Niño or climate change, but by a combination of climate signals acting at multiple timescales. In Brazil, the dry conditions present in 2013-2015 are primarily explained by year-to-year variability superimposed on decadal variability, but with little contribution of long-term trends. In contrast, the warm temperatures of 2014-2015 resulted from the compound effect of climate change, decadal and year-to-year climate variability. ZIKV response strategies made in Brazil during the drought concurrent with the 2015-2016 El Niño event, may require revision in light of the likely return of rainfall associated with the borderline La Niña event expected in 2016-2017. Temperatures are likely to remain warm given the importance of long term and decadal scale climate signals.

  8. QSRR Modeling for Metabolite Standards Analyzed by Two Different Chromatographic Columns Using Multiple Linear Regression.

    PubMed

    Zisi, Chrysostomi; Sampsonidis, Ioannis; Fasoula, Stella; Papachristos, Konstantinos; Witting, Michael; Gika, Helen G; Nikitas, Panagiotis; Pappa-Louisi, Adriani

    2017-02-09

    Modified quantitative structure retention relationships (QSRRs) are proposed and applied to describe two retention data sets: A set of 94 metabolites studied by a hydrophilic interaction chromatography system under organic content gradient conditions and a set of tryptophan and its major metabolites analyzed by a reversed-phase chromatographic system under isocratic as well as pH and/or simultaneous pH and organic content gradient conditions. According to the proposed modification, an additional descriptor is added to a conventional QSRR expression, which is the analyte retention time, tR(R), measured under the same elution conditions, but in a second chromatographic column considered as a reference one. The 94 metabolites were studied on an Amide column using a Bare Silica column as a reference. For the second dataset, a Kinetex EVO C18 and a Gemini-NX column were used, where each of them was served as a reference column of the other. We found in all cases a significant improvement of the performance of the QSRR models when the descriptor tR(R) was considered.

  9. QSRR Modeling for Metabolite Standards Analyzed by Two Different Chromatographic Columns Using Multiple Linear Regression

    PubMed Central

    Zisi, Chrysostomi; Sampsonidis, Ioannis; Fasoula, Stella; Papachristos, Konstantinos; Witting, Michael; Gika, Helen G.; Nikitas, Panagiotis; Pappa-Louisi, Adriani

    2017-01-01

    Modified quantitative structure retention relationships (QSRRs) are proposed and applied to describe two retention data sets: A set of 94 metabolites studied by a hydrophilic interaction chromatography system under organic content gradient conditions and a set of tryptophan and its major metabolites analyzed by a reversed-phase chromatographic system under isocratic as well as pH and/or simultaneous pH and organic content gradient conditions. According to the proposed modification, an additional descriptor is added to a conventional QSRR expression, which is the analyte retention time, tR(R), measured under the same elution conditions, but in a second chromatographic column considered as a reference one. The 94 metabolites were studied on an Amide column using a Bare Silica column as a reference. For the second dataset, a Kinetex EVO C18 and a Gemini-NX column were used, where each of them was served as a reference column of the other. We found in all cases a significant improvement of the performance of the QSRR models when the descriptor tR(R) was considered. PMID:28208794

  10. Analyzing the multiple functions of stereotypical behavior for students with autism: implications for assessment and treatment.

    PubMed

    Kennedy, C H; Meyer, K A; Knowles, T; Shukla, S

    2000-01-01

    We studied behavioral functions associated with stereotypical responses for students with autism. In Study 1, analogue functional analyses (attention, demand, no-attention, and recreation conditions) were conducted for 5 students. Results suggested that stereotypy was multiply determined or occurred across all assessment conditions. For 2 students, stereotypy was associated with positive and negative reinforcement and the absence of environmental stimulation. For 2 other students, stereotypy occurred at high levels across all experimental conditions. For the 5th student, stereotypy was associated with negative reinforcement and the absence of environmental stimulation. In Study 2, the stereotypy of 1 student was further analyzed on a function-by-function basis. Within a concurrent-schedules procedure, alternative responses were taught to the student using functional communication training. The results of Study 2 showed that similar topographies of stereotypy, based on qualitatively different reinforcers, were reduced only when differential reinforcement contingencies for alternative forms of communication were implemented for specific response-reinforcer relations. Our results suggest that the causes of stereotypy for students with autism are complex and that the presumed association between response topography and behavioral function may be less important than previously realized.

  11. A statistical model for analyzing the rotational error of single isocenter for multiple targets technique.

    PubMed

    Chang, Jenghwa

    2017-06-01

    To develop a statistical model that incorporates the treatment uncertainty from the rotational error of the single isocenter for multiple targets technique, and calculates the extra PTV (planning target volume) margin required to compensate for this error. The random vector for modeling the setup (S) error in the three-dimensional (3D) patient coordinate system was assumed to follow a 3D normal distribution with a zero mean, and standard deviations of σx , σy , σz . It was further assumed that the rotation of clinical target volume (CTV) about the isocenter happens randomly and follows a three-dimensional (3D) independent normal distribution with a zero mean and a uniform standard deviation of σδ . This rotation leads to a rotational random error (R), which also has a 3D independent normal distribution with a zero mean and a uniform standard deviation of σR equal to the product of σδπ180 and dI⇔T, the distance between the isocenter and CTV. Both (S and R) random vectors were summed, normalized, and transformed to the spherical coordinates to derive the Chi distribution with three degrees of freedom for the radial coordinate of S+R. PTV margin was determined using the critical value of this distribution for a 0.05 significance level so that 95% of the time the treatment target would be covered by the prescription dose. The additional PTV margin required to compensate for the rotational error was calculated as a function of σR and dI⇔T. The effect of the rotational error is more pronounced for treatments that require high accuracy/precision like stereotactic radiosurgery (SRS) or stereotactic body radiotherapy (SBRT). With a uniform 2-mm PTV margin (or σx = σy = σz = 0.715 mm), a σR = 0.328 mm will decrease the CTV coverage probability from 95.0% to 90.9%, or an additional 0.2-mm PTV margin is needed to prevent this loss of coverage. If we choose 0.2 mm as the threshold, any σR > 0.328 mm will lead to an extra PTV margin that cannot be ignored, and

  12. Impairment of Smooth Pursuit as a Marker of Early Multiple Sclerosis.

    PubMed

    Lizak, Nathaniel; Clough, Meaghan; Millist, Lynette; Kalincik, Tomas; White, Owen B; Fielding, Joanne

    2016-01-01

    Multiple sclerosis (MS) is a diffuse disease that disrupts wide-ranging cerebral networks. The control of saccades and smooth pursuit are similarly dependent upon widespread networks, with the assessment of pursuit offering an opportunity to examine feedback regulation. We sought to characterize pursuit deficits in MS and to examine their relationship with disease duration. Twenty healthy controls, 20 patients with a clinically isolated syndrome (CIS), and 40 patients with clinically definite MS (CDMS) participated. Thirty-six trials of Rashbass' step-ramp paradigm of smooth pursuit, evenly split by velocity (8.65°, 17.1°, and 25.9°/s) and ramp direction (left/right), were performed. Four parameters were measured: latency of pursuit onset, closed-loop pursuit gain, number of saccades, and summed saccade amplitudes during pursuit. For CDMS patients, these were correlated with disease duration and Expanded Disability Status Scale (EDSS) score. Closed-loop pursuit gain was significantly lower in CIS than controls at all speeds. CDMS gain was lower than controls at medium pursuit velocity. CDMS patients also displayed longer pursuit latency than controls at all velocities. All patients accumulated increased summed saccade amplitudes at slow and medium pursuit speeds, and infrequent high-amplitude saccades at the fast speed. No pursuit variable significantly correlated with EDSS or disease duration in CDMS patients. Smooth pursuit is significantly compromised in MS from onset. Low pursuit gain and increased saccadic amplitudes may be robust markers of disseminated pathology in CIS and in more advanced MS. Pursuit may be useful in measuring early disease.

  13. Interleukin-6 as inflammatory marker referring to multiple organ dysfunction syndrome in severely injured children

    PubMed Central

    2014-01-01

    Background Despite the suggestion that the inflammatory response in traumatized children is functionally unique, prognostic markers predicting pediatric multiple organ failure are lacking. We intended to verify whether Interleukin-6 (IL-6) displays a pivotal role in pediatric trauma similar to adults. Methods Traumatized children less than 18 years of age with an Injury Severity Score >9 points and consecutive admission to the hospital’s pediatric intensive care unit were included. Organ function was evaluated according to the score by Marshall et al. while IL-6 levels were measured repetitively every morning. Results 59 traumatized children were included (8.4 ± 4.4 years; 57.6% male gender). Incidence of MODS was 11.9%. No differences were found referring to age, gender, injury distribution or overall injury severity between children with and without MODS. Increased IL-6 levels during hospital admission were associated with injury severity (Spearman correlation: r = 0.522, p < 0.001), while an inconsistent association towards the development of MODS was proven at that time point (Spearman correlation: r = 0.180, p = 0.231; Pearson's correlation: r = 0.297, p = 0.045). However, increased IL-6 levels during the first two days were no longer associated with the injury severity but a significant correlation to MODS was measured. Conclusions The presented prospective study is the first providing evidence for a correlation of IL-6 levels with injury severity and the incidence of MODS in traumatized children. PMID:24589345

  14. Evidence of Multiple Disease Resistance (MDR) and implication of meta-analysis in marker assisted selection.

    PubMed

    Ali, Farhan; Pan, Qingchun; Chen, Genshen; Zahid, Kashif Rafiq; Yan, Jianbing

    2013-01-01

    Meta-analysis was performed for three major foliar diseases with the aim to find out the total number of QTL responsible for these diseases and depict some real QTL for molecular breeding and marker assisted selection (MAS) in maize. Furthermore, we confirmed our results with some major known disease resistance genes and most well-known gene family of nucleotide binding site (NBS) encoding genes. Our analysis revealed that disease resistance QTL were randomly distributed in maize genome, but were clustered at different regions of the chromosomes. Totally 389 QTL were observed for these three major diseases in diverse maize germplasm, out of which 63 QTL were controlling more than one disease revealing the presence of multiple disease resistance (MDR). 44 real-QTLs were observed based on 4 QTL as standard in a specific region of genome. We also confirmed the Ht1 and Ht2 genes within the region of real QTL and 14 NBS-encoding genes. On chromosome 8 two NBS genes in one QTL were observed and on chromosome 3, several cluster and maximum MDR QTL were observed indicating that the apparent clustering could be due to genes exhibiting pleiotropic effect. Significant relationship was observed between the number of disease QTL and total genes per chromosome based on the reference genome B73. Therefore, we concluded that disease resistance genes are abundant in maize genome and these results can unleash the phenomenon of MDR. Furthermore, these results could be very handy to focus on hot spot on different chromosome for fine mapping of disease resistance genes and MAS.

  15. Development of an In-Situ Data Logging System for Multiple Trace Gas Analyzers

    SciTech Connect

    Mioduszewski, John R.; Yu, Xiao-Ying

    2008-09-01

    A field deployable in-situ data logging system was developed at Pacific Northwest National Laboratory for trace gases including carbon monoxide (CO), ozone (O3), sulfur dioxide (SO2), and nitrogen oxides including nitric oxide, nitrogen dioxide, and odd nitrogens (NO/NO2/NOx). On-line data acquisition and calibration are essential to analysis of observables and data integrity. As such, a program was written to control the communication between the data logger and each analyzer in Logger Net, a program used to communicate with the data logger. Analog outputs were collected by a CR-23X Campbell data logger between July 2, 2007 and August 7, 2007 in Richland, Washington, with data being averaged every minute. A dynamic calibrator was used to calibrate the instruments using a gas standard with NIST-certified concentration. The National Oceanic and Atmospheric Administration’s HYSPLIT model was used to create a backward and forward trajectory of air during an episode of peak O3 to determine pollutant sources and sinks. Data collected through the duration of the sampling period revealed several observations. Concentrations of all trace gases were low, due in part to the scarcity of pollutant sources in the region. The average SO2 reading was less than 0.05 ppb over the period, whereas mixing ratios of 1-20 ppb are more common in rural-suburban environments. NO, NO2, and NOx averaged 0.3, 12.2, and 12.8 ppb, respectively, while the average CO was 228.5 ppb. Typical O3 in similar environments peaks at 80-150 ppb, but the highest mixing ratio of O3 observed was less than 45 ppb. HYSPLIT offered no apparent source for additional pollutants during the high O3 episode, but increased photochemistry due to high temperatures would explain the increase in O3. Both SO2 and NO readings registered near the detection limit of the instruments, and displayed a trend similar to background noise. The development of the data logging and display system for key trace gas species is an

  16. Comparison of genetic diversity and population structure of Pacific Coast whitebark pine across multiple markers

    Treesearch

    Andrew D. Bower; Bryce A. Richardson; Valerie Hipkins; Regina Rochefort; Carol Aubry

    2011-01-01

    Analysis of "neutral" molecular markers and "adaptive" quantitative traits are common methods of assessing genetic diversity and population structure. Molecular markers typically reflect the effects of demographic and stochastic processes but are generally assumed to not reflect natural selection. Conversely, quantitative (or "adaptive")...

  17. Short-term follow-up of chagasic patients after benznidazole treatment using multiple serological markers

    PubMed Central

    2011-01-01

    Background Conventional serological tests, using total soluble proteins or a cocktail of recombinant proteins from T. cruzi as antigens, are highly sensitive for Chagas disease diagnosis. This type of tests, however, does not seem to be reliable tools for short- and medium-term monitoring of the evolution of patients after antiparasitic treatment. The aim of the present study was to search for immunological markers that could be altered in the sera from Chagas disease patients after benznidazole treatment, and therefore have a potential predictive diagnostic value. Methods We analyzed the reactivity of sera from chagasic patients during different clinical phases of the disease against a series of immunodominant antigens, known as KMP11, PFR2, HSP70 and Tgp63. The reactivity of the sera from 46 adult Chronic Chagas disease patients living in a non-endemic country without vector transmission of T. cruzi (15 patients in the indeterminate stage, 16 in the cardiomiopathy stage and 16 in the digestive stage) and 22 control sera from non-infected subjects was analyzed. We also analyzed the response dynamics of sera from those patients who had been treated with benznidazole. Results Regardless of the stage of the sickness, the sera from chagasic patients reacted against KMP11, HSP70, PFR2 and Tgp63 recombinant proteins with statistical significance relative to the reactivity against the same antigens by the sera from healthy donors, patients with autoimmune diseases or patients suffering from tuberculosis, leprosy or malaria. Shortly after benznidazole treatment, a statistically significant decrease in reactivity against KMP11, HSP70 and PFR2 was observed (six or nine month). It was also observed that, following benznidazole treatment, the differential reactivity against these antigens co-relates with the clinical status of the patients. Conclusions The recombinant antigens KMP11, PFR2, Tgp63 and HSP70 are recognized by Chagas disease patients' sera at any clinical stage

  18. Short-term follow-up of chagasic patients after benzonidazole treatment using multiple serological markers.

    PubMed

    Fernández-Villegas, Ana; Pinazo, María Jesús; Marañón, Concepción; Thomas, M Carmen; Posada, Elizabeth; Carrilero, Bartolomé; Segovia, Manuel; Gascon, Joaquim; López, Manuel C

    2011-07-31

    Conventional serological tests, using total soluble proteins or a cocktail of recombinant proteins from T. cruzi as antigens, are highly sensitive for Chagas disease diagnosis. This type of tests, however, does not seem to be reliable tools for short- and medium-term monitoring of the evolution of patients after antiparasitic treatment. The aim of the present study was to search for immunological markers that could be altered in the sera from Chagas disease patients after benznidazole treatment, and therefore have a potential predictive diagnostic value. We analyzed the reactivity of sera from chagasic patients during different clinical phases of the disease against a series of immunodominant antigens, known as KMP11, PFR2, HSP70 and Tgp63. The reactivity of the sera from 46 adult Chronic Chagas disease patients living in a non-endemic country without vector transmission of T. cruzi (15 patients in the indeterminate stage, 16 in the cardiomiopathy stage and 16 in the digestive stage) and 22 control sera from non-infected subjects was analyzed. We also analyzed the response dynamics of sera from those patients who had been treated with benznidazole. Regardless of the stage of the sickness, the sera from chagasic patients reacted against KMP11, HSP70, PFR2 and Tgp63 recombinant proteins with statistical significance relative to the reactivity against the same antigens by the sera from healthy donors, patients with autoimmune diseases or patients suffering from tuberculosis, leprosy or malaria. Shortly after benznidazole treatment, a statistically significant decrease in reactivity against KMP11, HSP70 and PFR2 was observed (six or nine month). It was also observed that, following benznidazole treatment, the differential reactivity against these antigens co-relates with the clinical status of the patients. The recombinant antigens KMP11, PFR2, Tgp63 and HSP70 are recognized by Chagas disease patients' sera at any clinical stage of the disease. Shortly after

  19. Genetic Diversity of Namibian Pennisetum glaucum (L.) R. BR. (Pearl Millet) Landraces Analyzed by SSR and Morphological Markers

    PubMed Central

    McBenedict, Billy; Chimwamurombe, Percy; Kwembeya, Ezekeil; Maggs-Kölling, Gillian

    2016-01-01

    Current Pennisetum glaucum (L.) R. BR. cultivars in Namibia have overall poor performance posing a threat to the nation's food security because this crop is staple for over 70% of the Namibian population. The crop suffers from undesirable production traits such as susceptibility to diseases, low yield, and prolonged reproductive cycle. This study aimed to understand the genetic diversity of the crop in Namibia by simple sequence repeats (SSRs) and morphology analysis. A total of 1441 genotypes were collected from the National Gene Bank representing all the Namibian landraces. A sample of 96 genotypes was further analyzed by SSR using Shannon-Wiener diversity index and revealed a value of 0.45 indicating low genetic diversity. Ordination using Principal Coordinate Analysis (PCoA) on SSR data confirmed clusters generated by UPGMA for the 96 P. glaucum accessions. UPGMA phenograms of 29 morphological characterized genotypes were generated for SSR and morphology data and the two trees revealed 78% resemblance. Lodging susceptibility, tillering attitude, spike density, fodder yield potential, early vigour, and spike shape were the phenotypic characters upon which some clusters were based in both datasets. It is recommended that efforts should be made to widen the current gene pool in Namibia. PMID:27433479

  20. Multiple Lineages of Human Breast Cancer Stem/Progenitor Cells Identified by Profiling with Stem Cell Markers

    PubMed Central

    Hwang-Verslues, Wendy W.; Kuo, Wen-Hung; Chang, Po-Hao; Pan, Chi-Chun; Wang, Hsing-Hui; Tsai, Sheng-Ta; Jeng, Yung-Ming; Shew, Jin-Yu; Kung, John T.; Chen, Chung-Hsuan; Lee, Eva Y.-H. P.; Chang, King-Jen; Lee, Wen-Hwa

    2009-01-01

    Heterogeneity of cancer stem/progenitor cells that give rise to different forms of cancer has been well demonstrated for leukemia. However, this fundamental concept has yet to be established for solid tumors including breast cancer. In this communication, we analyzed solid tumor cancer stem cell markers in human breast cancer cell lines and primary specimens using flow cytometry. The stem/progenitor cell properties of different marker expressing-cell populations were further assessed by in vitro soft agar colony formation assay and the ability to form tumors in NOD/SCID mice. We found that the expression of stem cell markers varied greatly among breast cancer cell lines. In MDA-MB-231 cells, PROCR and ESA, instead of the widely used breast cancer stem cell markers CD44+/CD24-/low and ALDH, could be used to highly enrich cancer stem/progenitor cell populations which exhibited the ability to self renew and divide asymmetrically. Furthermore, the PROCR+/ESA+ cells expressed epithelial-mesenchymal transition markers. PROCR could also be used to enrich cells with colony forming ability from MB-361 cells. Moreover, consistent with the marker profiling using cell lines, the expression of stem cell markers differed greatly among primary tumors. There was an association between metastasis status and a high prevalence of certain markers including CD44+/CD24−/low, ESA+, CD133+, CXCR4+ and PROCR+ in primary tumor cells. Taken together, these results suggest that similar to leukemia, several stem/progenitor cell-like subpopulations can exist in breast cancer. PMID:20027313

  1. PL1 fusion gene: a novel visual selectable marker gene that confers tolerance to multiple abiotic stresses in transgenic tomato.

    PubMed

    Jin, Feng; Li, Shu; Dang, Lijie; Chai, Wenting; Li, Pengli; Wang, Ning Ning

    2012-10-01

    Visual selectable markers, including the purple color caused by the accumulation of anthocyanins, have been proposed for use as antibiotic-free alternatives. However, the excessive accumulation of anthocyanins seriously inhibits the growth and development of transgenic plants. In our study, the AtDWF4 promoter from Arabidopsis and the tomato LeANT1 gene, encoding a MYB transcription factor, were used to construct the PL1 fusion gene to test whether it could be used as a visual selectable marker gene for tomato transformation. All the PL1 transgenic shoots exhibited intense purple color on shoot induction medium. In the transgenic tomato plants, PL1 was highly expressed in the cotyledons, but expressed only slightly in the true leaves and other organs. The expression of PL1 had no significantly adverse effects on the growth or development of the transgenic tomato plants, and conferred tolerance to multiple abiotic stresses in them. With the “cut off green shoots” method, multiple independent 35S::GFP transgenic tomato lines were successfully obtained using PL1 as the selectable marker gene. These results suggest that PL1 has potential application of visual selectable marker gene for tomato transformation.

  2. The use of biochemical markers of bone remodeling in multiple myeloma: a report of the International Myeloma Working Group.

    PubMed

    Terpos, E; Dimopoulos, M A; Sezer, O; Roodman, D; Abildgaard, N; Vescio, R; Tosi, P; Garcia-Sanz, R; Davies, F; Chanan-Khan, A; Palumbo, A; Sonneveld, P; Drake, M T; Harousseau, J-L; Anderson, K C; Durie, B G M

    2010-10-01

    Lytic bone disease is a frequent complication of multiple myeloma (MM). Lytic lesions rarely heal and X-rays are of limited value in monitoring bone destruction during anti-myeloma or anti-resorptive treatment. Biochemical markers of bone resorption (amino- and carboxy-terminal cross-linking telopeptide of type I collagen (NTX and CTX, respectively) or CTX generated by matrix metalloproteinases (ICTP)) and bone formation provide information on bone dynamics and reflect disease activity in bone. These markers have been investigated as tools for evaluating the extent of bone disease, risk of skeletal morbidity and response to anti-resorptive treatment in MM. Urinary NTX, serum CTX and serum ICTP are elevated in myeloma patients with osteolytic lesions and correlate with advanced disease stage. Furthermore, urinary NTX and serum ICTP correlate with risk for skeletal complications, disease progression and overall survival. Bone markers have also been used for the early diagnosis of bone lesions. This International Myeloma Working Group report summarizes the existing data for the role of bone markers in assessing the extent of MM bone disease and in monitoring bone turnover during anti-myeloma therapies and provides information on novel markers that may be of particular interest in the near future.

  3. Clinical utility of biochemical markers of bone metabolism for improving the management of patients with advanced multiple myeloma.

    PubMed

    Lipton, Allan; Cook, Richard J; Coleman, Robert E; Smith, Matthew R; Major, Pierre; Terpos, Evangelos; Berenson, James R

    2007-03-01

    Osteolytic bone lesions from advanced multiple myeloma (MM) result in significant skeletal morbidity. Therefore, biochemical markers of bone metabolism, such as the N-terminal and C-terminal telopeptides of type I collagen, bone-specific alkaline phosphatase, and osteocalcin, have been investigated as tools for evaluating the extent of bone disease, risk of skeletal morbidity, and response to antiresorptive treatment. Several studies have shown that the majority of biochemical markers of bone metabolism are increased in patients with MM with osteolytic bone lesions, thus reflecting changes in bone metabolism associated with tumor growth. There is also a growing body of evidence that markers of bone metabolism correlate with the risk of skeletal complications, disease progression, and death. In addition, bone markers could potentially be used as a tool for early diagnosis of bone lesions. The aim of this review is to improve our understanding of bone markers as a clinical tool for the management of malignant bone disease in patients with MM.

  4. Multiple reaction analysis of cancer with different markers using silicon nanowire FET.

    PubMed

    Jang, Kuk Jin; Kim, Hyeyoun; Lee, Kook-Nyung; Lee, Min-Ho

    2013-01-01

    In this study, we have used newly developed Silicon nanowire (SiNW) arrays to evaluate their feasibility for the quantification of different markers of interests. We have quantified four different markers of PSA, EGF, IL-6, and VDBP. Each marker showed measurements in the range of 0.184∼17.79 ng/mL (PSA), 10 pg/mL∼10 ng/mL (EGF), 10 pg/mL∼50 ng/mL (IL-6), and 10 pg∼5 ng/mL (VDBP), respectively. For the experiment, we collected 10 different serum samples, 5 prostate cancer patients and 5 breast cancer patients, and measured and compared the resulting signal from the SiNW FET to serum sample from normal patients. As a result, we observed a meaningful pattern of markers associated with each type of cancer. In addition, we have measured the response signal of SiNWs conjugated with Epithelial cell adhesion molecules (EpCAM) markers against tumor cells as they interacted with those markers.

  5. Using molecular markers to map multiple quantitative trait loci: models for backcross, recombinant inbred, and doubled haploid progeny.

    PubMed

    Knapp, S J

    1991-03-01

    To maximize parameter estimation efficiency and statistical power and to estimate epistasis, the parameters of multiple quantitative trait loci (QTLs) must be simultaneously estimated. If multiple QTL affect a trait, then estimates of means of QTL genotypes from individual locus models are statistically biased. In this paper, I describe methods for estimating means of QTL genotypes and recombination frequencies between marker and quantitative trait loci using multilocus backcross, doubled haploid, recombinant inbred, and testcross progeny models. Expected values of marker genotype means were defined using no double or multiple crossover frequencies and flanking markers for linked and unlinked quantitative trait loci. The expected values for a particular model comprise a system of nonlinear equations that can be solved using an interative algorithm, e.g., the Gauss-Newton algorithm. The solutions are maximum likelihood estimates when the errors are normally distributed. A linear model for estimating the parameters of unlinked quantitative trait loci was found by transforming the nonlinear model. Recombination frequency estimators were defined using this linear model. Certain means of linked QTLs are less efficiently estimated than means of unlinked QTLs.

  6. Identification of Single- and Multiple-Class Specific Signature Genes from Gene Expression Profiles by Group Marker Index

    PubMed Central

    Tsai, Yu-Shuen; Aguan, Kripamoy; Pal, Nikhil R.; Chung, I-Fang

    2011-01-01

    Informative genes from microarray data can be used to construct prediction model and investigate biological mechanisms. Differentially expressed genes, the main targets of most gene selection methods, can be classified as single- and multiple-class specific signature genes. Here, we present a novel gene selection algorithm based on a Group Marker Index (GMI), which is intuitive, of low-computational complexity, and efficient in identification of both types of genes. Most gene selection methods identify only single-class specific signature genes and cannot identify multiple-class specific signature genes easily. Our algorithm can detect de novo certain conditions of multiple-class specificity of a gene and makes use of a novel non-parametric indicator to assess the discrimination ability between classes. Our method is effective even when the sample size is small as well as when the class sizes are significantly different. To compare the effectiveness and robustness we formulate an intuitive template-based method and use four well-known datasets. We demonstrate that our algorithm outperforms the template-based method in difficult cases with unbalanced distribution. Moreover, the multiple-class specific genes are good biomarkers and play important roles in biological pathways. Our literature survey supports that the proposed method identifies unique multiple-class specific marker genes (not reported earlier to be related to cancer) in the Central Nervous System data. It also discovers unique biomarkers indicating the intrinsic difference between subtypes of lung cancer. We also associate the pathway information with the multiple-class specific signature genes and cross-reference to published studies. We find that the identified genes participate in the pathways directly involved in cancer development in leukemia data. Our method gives a promising way to find genes that can involve in pathways of multiple diseases and hence opens up the possibility of using an existing

  7. Identification of single- and multiple-class specific signature genes from gene expression profiles by group marker index.

    PubMed

    Tsai, Yu-Shuen; Aguan, Kripamoy; Pal, Nikhil R; Chung, I-Fang

    2011-01-01

    Informative genes from microarray data can be used to construct prediction model and investigate biological mechanisms. Differentially expressed genes, the main targets of most gene selection methods, can be classified as single- and multiple-class specific signature genes. Here, we present a novel gene selection algorithm based on a Group Marker Index (GMI), which is intuitive, of low-computational complexity, and efficient in identification of both types of genes. Most gene selection methods identify only single-class specific signature genes and cannot identify multiple-class specific signature genes easily. Our algorithm can detect de novo certain conditions of multiple-class specificity of a gene and makes use of a novel non-parametric indicator to assess the discrimination ability between classes. Our method is effective even when the sample size is small as well as when the class sizes are significantly different. To compare the effectiveness and robustness we formulate an intuitive template-based method and use four well-known datasets. We demonstrate that our algorithm outperforms the template-based method in difficult cases with unbalanced distribution. Moreover, the multiple-class specific genes are good biomarkers and play important roles in biological pathways. Our literature survey supports that the proposed method identifies unique multiple-class specific marker genes (not reported earlier to be related to cancer) in the Central Nervous System data. It also discovers unique biomarkers indicating the intrinsic difference between subtypes of lung cancer. We also associate the pathway information with the multiple-class specific signature genes and cross-reference to published studies. We find that the identified genes participate in the pathways directly involved in cancer development in leukemia data. Our method gives a promising way to find genes that can involve in pathways of multiple diseases and hence opens up the possibility of using an existing

  8. [Clinical characteristics of bone disease in multiple myeloma and clinical significance of monitoring bone metabolic markers].

    PubMed

    Chu, B; Lu, M Q; Wu, M Q; Shi, L; Fu, L N; Gao, S; Fang, L J; Xiang, Q Q; Bao, L

    2016-05-17

    To observe the clinical characteristics of bone disease in patients with multiple myeloma (MM) and the clinical significance of monitoring bone metabolic markers. The data of 178 MM cases newly diagnosed in Beijing Ji Shui Tan Hospital from January 2009 to June 2014 were reviewed to analysis the types and classification of bone disease and to observe the clinical characteristics of patients with different grades of bone disease. The levels of bone metabolic markers total procollagen type Ⅰ N-terminal peptide (tPINP) and β C-terminal telopeptide of type Ⅰ collagen (β-CTX) were monitored regularly in the two years following treatment in 66 cases. (1) Among the 178 newly diagnosed MM cases, 167 cases complained of pain in bones on first visit, 35 cases combined with hypercalcemia, 83 cases combined with osteoporosis, 154 cases combined with osteolytic bone destruction, and 73 cases combined with pathologic fracture. The most common osteolytic location was the spine. The most common fracture sites was the spine. (2) According to bone disease grading, the 178 cases were divided into group A (bone grade 0-2, n=51) and group B(bone grade 3-4, n=127). There were no significant differences between group A and group B in gender, median age, therapeutic effect/ineffec, median overall survival, median progress-free survival, mean serum lactic dehydrogenase, mean albumin, urine light chains and serum creatinine(all P>0.05). Compared with group A, group B had lower hemoglobin level[(99.78±29.93)vs (108.84±29.30) g/L], and higher blood calcium level[(2.47±0.40)vs (2.30±0.29) mmol/L], serum β2-microglobuin level[(6.04±4.84)vs (4.12±3.97)mg/L], and bone marrow plasma cells percentage(33.30%±24.87% vs 23.51%±22.67%)(all P<0.05). (3) Before treatment, the levels of β-CTX and tPINP in patients of group B(n=47) were higher than those in group A(n=19)(median 0.78 vs 0.42 μg/L, 60.95 vs 43.47 μg/L, both P<0.05). The ratio of β-CTX /tPINP in group B was higher than that

  9. Targeted unlabeled multiple reaction monitoring analysis of cell markers for the study of sample heterogeneity in isolated rat brain cortical microvessels.

    PubMed

    Gomez-Zepeda, David; Chaves, Catarina; Taghi, Méryam; Sergent, Philippe; Liu, Wang-Qing; Chhuon, Cérina; Vidal, Michel; Picard, Martin; Thioulouse, Elizabeth; Broutin, Isabelle; Guerrera, Ida-Chiara; Scherrmann, Jean-Michel; Parmentier, Yannick; Decleves, Xavier; Menet, Marie-Claude

    2017-08-01

    Liquid chromatography coupled to tandem mass spectrometry-based targeted absolute protein quantification (in fmol of the analyte protein per μg of total protein) is employed for the molecular characterization of the blood-brain barrier using isolated brain microvessels. Nevertheless, the heterogeneity of the sample regarding the levels of different cells co-isolated within the microvessels and bovine serum albumin (BSA) contamination (from buffers) are not always evaluated. We developed an unlabeled targeted liquid chromatography coupled to tandem mass spectrometry method to survey the levels of endothelial cells (ECs), astrocytes, and pericytes, as well as BSA contaminant in rat cortical microvessels. Peptide peak identities were evaluated using a spectral library and chromatographic parameters. Sprague-Dawley rat microvessels obtained on three different days were analyzed with this method complemented by an absolute quantification multiple reaction monitoring method for transporter proteins P-gp, Bcrp, and Na(+) /K(+) ATPase pump using stable isotope labeled peptides as internal standard. Inter-day differences in the cell markers and BSA contamination were observed. Levels of cell markers correlated positively between each other. Then, the correlation between cell marker proteins and transporter proteins was evaluated to choose the best EC marker protein for protein quantification normalization. The membrane protein Pecam-1 showed a very high correlation with the EC-specific transporter P-gp (Pearson product-moment correlation coefficient (r) > 0.89) and moderate to high with Bcrp (r ≥ 0.77), that can be found also in pericytes and astrocytes. Therefore, Pecam-1 was selected as a marker for the normalization of the quantification of the proteins of endothelial cells. © 2017 International Society for Neurochemistry.

  10. Development of a kinematic 3D carpal model to analyze in vivo soft-tissue interaction across multiple static postures.

    PubMed

    Marai, G; Crisco, Joseph J; Laidlaw, David H

    2009-01-01

    We developed a subject-specific kinematic model to analyze in vivo soft-tissue interaction in the carpus in static, unloaded postures. The bone geometry was extracted from a reference computed tomography volume image. The soft-tissue geometry, including cartilage and ligament tissues, was computationally modeled based on kinematic constraints; the constraints were extracted from multiple computed tomography scans corresponding to different carpal postures. The data collected in vivo was next coupled with numerical simulation in order to analyze the role of soft-tissues in different postures. The resulting model extends the state of biomechanical modeling by incorporating soft-tissue constraints across the carpus range of motion, while successfully using only physiological constraints. The model results suggest that soft-tissue wrapping constraints have substantial impact on carpus stability.

  11. High apelin levels could be used as a diagnostic marker in multiple myeloma: A comparative study.

    PubMed

    Maden, Muhammet; Pamuk, Omer Nuri; Pamuk, Gulsum Emel

    2016-01-01

    Apelin/APJ system regulates angiogenesis and is overexpressed in some malignancies. Apelin can induce lymphangiogenesis and lymph node metastasis. We evaluated apelin levels in multiple myeloma (MM) and non-Hodgkin lymphoma (NHL); and analyzed the association between apelin levels and clinical findings. We included consecutive 29 MM, 31 NHL patients, and 19 healthy controls. Patients' demographic and clinical features, treatment modalities, and responses were recorded from hospital records. Plasma apelin was determined by enzyme-linked immunosorbent assay (ELISA). MM patients had significantly higher plasma apelin level than NHL and healthy control groups (p< 0.001). Apelin level in NHL group was similar to controls (p> 0.05). ROC curve analysis showed that the area under the curve value for apelin level in MM was 0.842 ng/ml (95%CI: 0.739-0.945, p< 0.001). Plasma apelin level ≥ 0.827 ng/ml had 76% sensitivity and 86% specificity for the diagnosis of MM. Multivariate Cox regression analysis showed that MM patients with high apelin level had better prognosis and patients with advanced stage of disease (ISS-3) had significantly poor prognosis when compared to others. In the MM group, apelin level correlated negatively with LDH (r = -0.39, p= 0.038). In MM, plasma apelin level was significantly higher than in NHL and control groups. Apelin could be playing a role in MM pathogenesis; and apelin level could be used as a diagnostic and prognostic biomarker in MM.

  12. Fast and accurate localization of multiple RF markers for tracking in MRI-guided interventions.

    PubMed

    Galassi, Francesca; Brujic, Djordje; Rea, Marc; Lambert, Nicholas; Desouza, Nandita; Ristic, Mihailo

    2015-02-01

    A new method for 3D localization of N fiducial markers from 1D projections is presented and analysed. It applies to semi-active markers and active markers using a single receiver channel. The novel algorithm computes candidate points using peaks in three optimally selected projections and removes fictitious points by verifying detected peaks in additional projections. Computational complexity was significantly reduced by avoiding cluster analysis, while higher accuracy was achieved by using optimal projections and by applying Gaussian interpolation in peak detection. Computational time, accuracy and robustness were analysed through Monte Carlo simulations and experiments. The method was employed in a prototype MRI guided prostate biopsy system and used in preclinical experiments. The computational time for 6 markers was better than 2 ms, an improvement of up to 100 times, compared to the method by Flask et al. (J Magn Reson Imaging 14(5):617-627, 2001). Experimental maximum localization error was lower than 0.3 mm; standard deviation was 0.06 mm. Targeting error was about 1 mm. Tracking update rate was about 10 Hz. The proposed method is particularly suitable in systems requiring any of the following: high frame rate, tracking of three or more markers, data filtering or interleaving.

  13. Multiple congenital abnormalities in a newborn with two supernumerary marker chromosomes derived from chromosome 14.

    PubMed

    Faas, B H W; Van Der Deure, J; Wunderink, M I; Merkx, G; Brunner, H G

    2006-01-01

    Pure partial duplication or triplication of the proximal part of chromosome 14 has been reported in only 4 patients. Other individuals with a duplication or triplication of this region have additional chromosome imbalances. We present a new case with a supernumerary marker chromosome in all blood cells and in 35% of the cells an additional smaller marker chromosome. Both markers appeared to be derived from chromosome 14 (del(14)(q21.2) in all cells and del(14)(q11.2) in 35% of the cells). This results in a partial duplication of the proximal region of chromosome 14, combined with a mosaic partial triplication of a smaller segment of the same region. In this paper, we compare the clinical features of this case to those of cases from the literature. Although most of the patients from literature were unbalanced translocation carriers, their clinical features were comparable, except from renal abnormalities.

  14. Corpus callosum atrophy as a marker of clinically meaningful cognitive decline in secondary progressive multiple sclerosis. Impact on employment status.

    PubMed

    Papathanasiou, Athanasios; Messinis, Lambros; Zampakis, Petros; Papathanasopoulos, Panagiotis

    2017-09-01

    Cognitive impairment in Multiple Sclerosis (MS) is more frequent and pronounced in secondary progressive MS (SPMS). Cognitive decline is an important predictor of employment status in patients with MS. Magnetic Resonance Imaging (MRI) markers have been used to associate tissue damage with cognitive dysfunction. The aim of the study was to designate the MRI marker that predicts cognitive decline in SPMS and explore its effect on employment status. 30 SPMS patients and 30 healthy participants underwent neuropsychological assessment using the Trail Making Test (TMT) parts A and B, semantic and phonological verbal fluency task and a computerized cognitive screening battery (Central Nervous System Vital Signs). Employment status was obtained as a quality of life measure. Brain MRI was performed in all participants. We measured total lesion volume, third ventricle width, thalamic and corpus callosum atrophy. The frequency of cognitive decline for our SPMS patients was 80%. SPMS patients differed significantly from controls in all neuropsychological measures. Corpus callosum area was correlated with cognitive flexibility, processing speed, composite memory, executive functions, psychomotor speed, reaction time and phonological verbal fluency task. Processing speed and composite memory were the most sensitive markers for predicting employment status. Corpus callosum area was the most sensitive MRI marker for memory and processing speed. Corpus callosum atrophy predicts a clinically meaningful cognitive decline, affecting employment status in our SPMS patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Non-malignant T-cells lacking multiple pan-T markers can be found in lymph nodes.

    PubMed

    Wang, Wei; Gao, Li; Gong, Ming; Tang, Yin; Li, Yan; Zhang, Wen-Tao; Huang, Fan-Zhou; Zhang, Chun-Xia; Chen, Yan-Rong; Gao, Ya-Yue; Li, Zhen-Ling; Ma, Yi-Gai

    2018-01-01

    In order to observe and ascertain the properties of a sub-group of T cells in the lymph node (LN) from seven patients who did not suffer from T cell lymphoproliferative disorders (T-LPDs), the expression levels of several pan-T markers were evaluated by multiparameter flow cytometry (FC) and the clonality of these T-cells was evaluated by both FC analysis and PCR assessment. It turned out that multiple pan-T-cell markers such as CD2, CD5 and CD7 were found to be lost in these T cells. The majority of them were positive for TCRαβ, only a minority of them being positive for TCRγδ. A subset of these T-cells were positive for CD4 or CD8 or dual-negative for CD4 and CD8. Oligoclonality was detected in one case by FC, while clonal TCR rearrangement was detected in three cases. Absence of multiple pan-T-cell markers could be found in benign T cells in LNs.

  16. Bi-allelic inactivation is more prevalent at relapse in multiple myeloma, identifying RB1 as an independent prognostic marker

    PubMed Central

    Chavan, S S; He, J; Tytarenko, R; Deshpande, S; Patel, P; Bailey, M; Stein, C K; Stephens, O; Weinhold, N; Petty, N; Steward, D; Rasche, L; Bauer, M; Ashby, C; Peterson, E; Ali, S; Ross, J; Miller, V A; Stephens, P; Thanendrarajan, S; Schinke, C; Zangari, M; van Rhee, F; Barlogie, B; Mughal, T I; Davies, F E; Morgan, G J; Walker, B A

    2017-01-01

    The purpose of this study is to identify prognostic markers and treatment targets using a clinically certified sequencing panel in multiple myeloma. We performed targeted sequencing of 578 individuals with plasma cell neoplasms using the FoundationOne Heme panel and identified clinically relevant abnormalities and novel prognostic markers. Mutational burden was associated with maf and proliferation gene expression groups, and a high-mutational burden was associated with a poor prognosis. We identified homozygous deletions that were present in multiple myeloma within key genes, including CDKN2C, RB1, TRAF3, BIRC3 and TP53, and that bi-allelic inactivation was significantly enriched at relapse. Alterations in CDKN2C, TP53, RB1 and the t(4;14) were associated with poor prognosis. Alterations in RB1 were predominantly homozygous deletions and were associated with relapse and a poor prognosis which was independent of other genetic markers, including t(4;14), after multivariate analysis. Bi-allelic inactivation of key tumor suppressor genes in myeloma was enriched at relapse, especially in RB1, CDKN2C and TP53 where they have prognostic significance. PMID:28234347

  17. Diagnostic value of multiple tumor markers for patients with esophageal carcinoma.

    PubMed

    Zhang, Jun; Zhu, Zhenli; Liu, Yan; Jin, Xueyuan; Xu, Zhiwei; Yu, Qiuyan; Li, Ke

    2015-01-01

    Various studies assessing the diagnostic value of serum tumor markers in patients with esophageal cancer remain controversial. This study aims to comprehensively and quantitatively summarize the potential diagnostic value of 5 serum tumour markers in esophageal cancer. We systematically searched PubMed, Embase, Chinese National Knowledge Infrastructure (CNKI) and Chinese Biomedical Database (CBM), through February 28, 2013, without language restriction. Studies were assessed for quality using QUADAS (quality assessment of studies of diagnostic accuracy). The positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were pooled separately and compared with overall accuracy measures using diagnostic odds ratios (DORs) and symmetric summary receiver operating characteristic (SROC) curves. Of 4391 studies initially identified, 44 eligible studies including five tumor markers met the inclusion criteria for the meta-analysis, while meta-analysis could not be conducted for 12 other tumor markers. Approximately 79.55% (35/44) of the included studies were of relatively high quality (QUADAS score≥7). The summary estimates of the positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) for diagnosing EC were as follows: CEA, 5.94/0.76/9.26; Cyfra21-1, 12.110.59/22.27; p53 antibody, 6.71/0.75/9.60; SCC-Ag, 7.66/0.68/12.41; and VEGF-C, 0.74/0.37/8.12. The estimated summary receiver operating characteristic curves showed that the performance of all five tumor markers was reasonable. The current evidence suggests that CEA, Cyfra21-1, p53, SCC-Ag and VEGF-C have a potential diagnostic value for esophageal carcinoma.

  18. Simultaneous quantitative detection of multiple tumor markers with a rapid and sensitive multicolor quantum dots based immunochromatographic test strip.

    PubMed

    Wang, Chunying; Hou, Fei; Ma, Yicai

    2015-06-15

    A novel multicolor quantum dots (QDs) based immunochromatographic test strip (ICTS) was developed for simultaneous quantitative detection of multiple tumor markers, by utilizing alpha fetoprotein (AFP) and carcinoembryonic antigen (CEA) as models. The immunosensor could realize simultaneous quantitative detection of tumor markers with only one test line and one control line on the nitrocellulose membrane (NC membrane) due to the introduction of multicolor QDs. In this method, a mixture of mouse anti-AFP McAb and mouse anti-CEA McAb was coated on NC membrane as test line and goat anti-mouse IgG antibody was coated as control line. Anti-AFP McAb-QDs546 conjugates and anti-CEA McAb-QDs620 conjugates were mixed and applied to the conjugate pad. Simultaneous quantitative detection of multiple tumor markers was achieved by detecting the fluorescence intensity of captured QDs labels on test line and control line using a test strip reader. Under the optimum conditions, AFP and CEA could be detected as low as 3 ng/mL and 2 ng/mL in 15 min with a sample volume of 80 μL, and no obvious cross-reactivity was observed. The immunosensor was validated with 130 clinical samples and in which it exhibited high sensitivity (93% for AFP and 87% for CEA) and specificity (94% for AFP and 97% for CEA). The immunosensor also demonstrated high recoveries (87.5-113% for AFP and 90-97.3% for CEA) and low relative standard deviations (RSDs) (2.8-6.2% for AFP and 4.9-9.6% for CEA) when testing spiked human serum. This novel multicolor QDs based ICTS provides an easy and rapid, simultaneous quantitative detecting strategy for point-of-care testing of tumor markers. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Induction and expression of mutations at multiple drug-resistance marker loci in Chinese hamster ovary cells

    SciTech Connect

    Adair, G.M.; Carver, J.H.

    1983-01-01

    We observed quantitative and qualitative differences in the mutability and mutagen-specificity of various drug-resistance marker loci in Chinese hamster ovary (THO) cells, which suggest that mammalian gene loci may differ in their relative mutability by a given mutagenic agent. We have used the CHO-AT3-2 multiple-marker mutagenesis assay system to examine the dose-dependent induction and kinetics of expression of mutations at four well-characterized, drug-resistance marker loci, after treatment with chemical agents which produce various types of DNA damage. The CHO-AT3-2 subline allows simultaneous quantitation and direct comparison of induced mutation frequencies at the hgprt, oua (Na/sup +//K/sup +/ ATPase), aprt, and tk loci. The agents tested in this study included ethyl methanesulfonate, methyl methanesulfonate, mitomycin C, ICR-191, benzo(a)pyrene, and dimethylnitrosamine. The expression kinetics and optimal expression times for each drug-resistance marker were determined in dose-response experiments in which cells from mutagen-treated populations were plated at 1-2-day intervals over a period of 10 days following mutagenesis. Comparison of induced mutation frequencies for each drug-resistance marker after mutagen treatments yielding equivalent cell survivals (equitoxic doses resulting in relative cell survivals of 0.37) revealed locus-specific differences in the relative mutagenicities of the agents tested. These results indicate that the apparent mutagenicity of a particular agent at a single genetic locus may not necessarily be an accurate indicator of that agent's mutagenic potential for the genome as a whole.

  20. Multiple RT-PCR markers for the detection of circulating tumour cells of metastatic canine mammary tumours.

    PubMed

    da Costa, A; Kohn, B; Gruber, A D; Klopfleisch, R

    2013-04-01

    In humans, detection of circulating tumour cells (CTCs) using nucleic acid-based methods such as reverse transcription polymerase chain reaction (RT-PCR) has proven to be of prognostic relevance. However, similar procedures are still lacking in veterinary oncology. To assess the correlation of CTC markers with the metastatic potential of canine mammary tumours, 120 peripheral blood samples from bitches with mammary carcinomas with (group 1) and without (group 2) histological evidence of vascular invasion and/or presence of lymph node metastases and mammary adenomas (group 3) were analyzed. Blood samples were collected in EDTA tubes and RNA was extracted within 48 h. Subsequently, the samples were tested by RT-PCR for a panel of seven CTC mRNA markers. CRYAB was the most sensitive single marker with a sensitivity of 35% and also the most specific marker with a specificity of 100% to detect group 1 blood samples. A multimarker assay combining four genes enhanced the sensitivity up to 77.5%, but decreased the specificity to 80%. CRYAB appeared to be highly specific but only moderately sensitive at detecting blood samples from dogs with metastatic tumours and detection significantly correlated with vascular invasion of primary mammary tumours. However, a multimarker assay of four genes significantly enhanced the sensitivity of the assay and is therefore preferable for CTC detection. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Analyzing latent state-trait and multiple-indicator latent growth curve models as multilevel structural equation models

    PubMed Central

    Geiser, Christian; Bishop, Jacob; Lockhart, Ginger; Shiffman, Saul; Grenard, Jerry L.

    2013-01-01

    Latent state-trait (LST) and latent growth curve (LGC) models are frequently used in the analysis of longitudinal data. Although it is well-known that standard single-indicator LGC models can be analyzed within either the structural equation modeling (SEM) or multilevel (ML; hierarchical linear modeling) frameworks, few researchers realize that LST and multivariate LGC models, which use multiple indicators at each time point, can also be specified as ML models. In the present paper, we demonstrate that using the ML-SEM rather than the SL-SEM framework to estimate the parameters of these models can be practical when the study involves (1) a large number of time points, (2) individually-varying times of observation, (3) unequally spaced time intervals, and/or (4) incomplete data. Despite the practical advantages of the ML-SEM approach under these circumstances, there are also some limitations that researchers should consider. We present an application to an ecological momentary assessment study (N = 158 youths with an average of 23.49 observations of positive mood per person) using the software Mplus (Muthén and Muthén, 1998–2012) and discuss advantages and disadvantages of using the ML-SEM approach to estimate the parameters of LST and multiple-indicator LGC models. PMID:24416023

  2. Bence Jones proteinuria in smoldering multiple myeloma as a predictor marker of progression to symptomatic multiple myeloma.

    PubMed

    González-Calle, V; Dávila, J; Escalante, F; de Coca, A G; Aguilera, C; López, R; Bárez, A; Alonso, J M; Hernández, R; Hernández, J M; de la Fuente, P; Puig, N; Ocio, E M; Gutiérrez, N C; García-Sanz, R; Mateos, M V

    2016-10-01

    The diagnosis of smoldering multiple myeloma (SMM) includes patients with a heterogeneous risk of progression to active multiple myeloma (MM): some patients will never progress, whereas others will have a high risk of progression within the first 2 years. Therefore, it is important to improve risk assessment at diagnosis. We conducted a retrospective study in a large cohort of SMM patients, in order to investigate the role of Bence Jones (BJ) proteinuria at diagnosis in the progression to active MM. We found that SMM patients presenting with BJ proteinuria had a significantly shorter median time to progression (TTP) to MM compared with patients without BJ proteinuria (22 vs 88 months, respectively; hazard ratio=2.3, 95% confidence interval=1.4-3.9, P=0.002). We also identified risk subgroups based on the amount of BJ proteinuria: ⩾500 mg/24 h, <500 mg/24 h and without it, with a significantly different median TTP (13, 37 and 88 months, P<0.001). Thus, BJ proteinuria at diagnosis is an independent variable of progression to MM that identifies a subgroup of high-risk SMM patients (51% risk of progression at 2 years) and ⩾500 mg of BJ proteinuria may allow, if validated in another series, to reclassify these patients to MM requiring therapy before the end-organ damage development.

  3. The genotypes of citrus tristeza virus isolates from China revealed by sequence analysis of multiple molecular markers.

    PubMed

    Wu, Guan-Wei; Pan, Song; Wang, Guo-Ping; Tang, Min; Liu, Yong; Yang, Fan; Hong, Ni

    2013-01-01

    The genotypes of ten citrus tristeza virus (CTV) isolates from central China were determined by examining multiple molecular markers (MMMs) using 11 primer pairs. The results revealed that one isolate contained a single T30 genotype, two isolates contained a single VT genotype, and the other seven isolates were mixtures of two or more genotypes. Sequence analysis of amplified MMMs showed a high genetic diversity in Chinese CTV populations. The genotypes resembling T36, RB and B165 were identified from Chinese CTV isolates for the first time. Our results suggest that genotype assignment of CTV cannot be based solely on the amplification profiles of MMMs, and sequencing of MMMs is required.

  4. Analyzing multiple endpoints in a confirmatory randomized clinical trial-an approach that addresses stratification, missing values, baseline imbalance and multiplicity for strictly ordinal outcomes.

    PubMed

    Sun, Hengrui; Kawaguchi, Atsushi; Koch, Gary

    2017-03-01

    Confirmatory randomized clinical trials with a stratified design may have ordinal response outcomes, ie, either ordered categories or continuous determinations that are not compatible with an interval scale. Also, multiple endpoints are often collected when 1 single endpoint does not represent the overall efficacy of the treatment. In addition, random baseline imbalances and missing values can add another layer of difficulty in the analysis plan. Therefore, the development of an approach that provides a consolidated strategy to all issues collectively is essential. For a real case example that is from a clinical trial comparing a test treatment and a control for the pain management for patients with osteoarthritis, which has all aforementioned issues, multivariate Mann-Whitney estimators with stratification adjustment are applicable to the strictly ordinal responses with stratified design. Randomization based nonparametric analysis of covariance is applied to account for the possible baseline imbalances. Several approaches that handle missing values are provided. A global test followed by a closed testing procedure controls the family wise error rate in the strong sense for the analysis of multiple endpoints. Four outcomes indicating joint pain, stiffness, and functional status were analyzed collectively and also individually through the procedures. Treatment efficacy was observed in the combined endpoint as well as in the individual endpoints. The proposed approach is effective in addressing the aforementioned problems simultaneously and straightforward to implement.

  5. Tall fescue genomic SSR markers: development and transferability across multiple grass species.

    PubMed

    Saha, Malay C; Cooper, John D; Mian, M A Rouf; Chekhovskiy, Konstantin; May, Gregory D

    2006-11-01

    Simple sequence repeat (SSR) markers are highly informative and widely used for genetic and breeding studies. Currently, a very limited number of SSR markers are available for tall fescue (Festuca arundinacea Schreb.) and other forage grass species. A tall fescue genomic library enriched in (GA/CT)( n ) repeats was used to develop primer pairs (PPs) flanking SSRs and assess PP functionality across different forage, cereal, and turf grass species. A total of 511 PPs were developed and assessed for their utility in six different grass species. The parents and a subset of a tall fescue mapping population were used to select PPs for mapping in tall fescue. Survey results revealed that 48% (in rice) to 66% (in tall fescue) of the PPs produced clean SSR-type amplification products in different grass species. Polymorphism rates were higher in tall fescue (68%) compared to other species (46% ryegrass, 39% wheat, and 34% rice). A set of 194 SSR loci (38%) were identified which amplified across all six species. Loci segregating in the tall fescue mapping population were grouped as loci segregating from the female parent (HD28-56, 37%), the male parent (R43-64, 37%), and both parents (26%). Three percent of the loci that were polymorphic between parents were monomorphic in the pseudo F1 mapping population and the remaining loci segregated. Sequencing of amplified products obtained from PP NFFAG428 revealed a very high level of sequence similarity among the grass species under study. Our results are the first report of genomic SSR marker development from tall fescue and they demonstrate the usefulness of these SSRs for genetic linkage mapping in tall fescue and cross-species amplification.

  6. Tumor necrosis factor beta NcoI polymorphism is associated with inflammatory and metabolic markers in multiple sclerosis patients.

    PubMed

    Kallaur, Ana Paula; Oliveira, Sayonara Rangel; Simão, Andréa Name Colado; de Almeida, Elaine Regina Delicato; Morimoto, Helena Kaminami; Alfieri, Daniela Frizon; Pereira, Wildea Lice de Carvalho Jennings; Borelli, Sueli Donizete; Kaimen-Maciel, Damácio Ramon; Maes, Michael; Reiche, Edna Maria Vissoci

    2014-11-15

    To evaluate the association between the tumor necrosis factor beta (TNF-β) NcoI polymorphism and inflammatory and metabolic markers in patients with multiple sclerosis (MS) patients and the association of these markers with disease disability, a 782 base-pair fragment of the TNF-β gene was amplified from genomic DNA and digested with the NcoI restriction enzyme. The serum levels of numerous cytokines (IL-1β, IL-12, IL-6, TNF-α, IFN-γ, IL-4, IL-10, and IL-17) serum lipid levels, plasma insulin levels, and the Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) levels were evaluated in 123 female and 43 male patients with MS. Females carrying the TNFB2/B2 genotype presented with decreased IL-4 and IL-10 levels and increased TNF-α, glucose, insulin, and HOMA-IR levels; moreover, there were positive correlations between EDSS and glucose and between EDSS and HOMA-IR in these females. Males carrying the TNFB2/B2 genotype exhibited increased levels of TNF-α, IFN-γ, and IL-17 (p=0.0326) and decreased levels of IL-4, IL-10, insulin, and HOMA-IR; there was a positive correlation between EDSS and TNF-α levels. The TNFB2/B2 genotype of TNF-β NcoI polymorphism was associated with increased inflammatory and metabolic markers and this association was different according to sex of MS patients.

  7. The renal protective effect of angiotensin receptor blockers depends on intra-individual response variation in multiple risk markers

    PubMed Central

    Schievink, Bauke; de Zeeuw, Dick; Parving, Hans-Henrik; Rossing, Peter; Lambers Heerspink, Hiddo Jan

    2015-01-01

    Aims Angiotensin receptor blockers (ARBs) are renoprotective and targeted to blood pressure. However, ARBs have multiple other (off-target) effects which may affect renal outcome. It is unknown whether on-target and off-target effects are congruent within individuals. If not, this variation in short term effects may have important implications for the prediction of individual long term renal outcomes. Our aim was to assess intra-individual variability in multiple parameters in response to ARBs in type 2 diabetes. Methods Changes in systolic blood pressure (SBP), albuminuria, potassium, haemoglobin, cholesterol and uric acid after 6 months of losartan treatment were assessed in the RENAAL database. Improvement in predictive performance of renal outcomes (ESRD or doubling serum creatinine) for each individual using ARB-induced changes in all risk markers was assessed by the relative integrative discrimination index (RIDI). Results SBP response showed high variability (mean –5.7 mmHg, 5th to 95th percentile –36.5 to +24.0 mmHg) between individuals. Changes in off-target parameters also showed high variability between individuals. No congruency was observed between responses to losartan in multiple parameters within individuals. Using individual responses in all risk markers significantly improved renal risk prediction (RIDI 30.4%, P < 0.01) compared with using only SBP changes. Results were successfully replicated in two independent trials with irbesartan, IDNT and IRMA-2. Conclusions In this post hoc analysis we showed that ARBs have multiple off-target effects which vary between and within individuals. Combining all ARB-induced responses beyond SBP provides a more accurate prediction of who will benefit from ARB therapy. Prospective trials are required to validate these findings. PMID:25872610

  8. Calorimetric markers of Bence Jones and nonsecretory multiple myeloma serum proteome.

    PubMed

    Todinova, Svetla; Krumova, Sashka; Radoeva, Ralitsa; Gartcheva, Lidia; Taneva, Stefka G

    2014-12-16

    The present work provides a thermodynamic description of blood serum from patients diagnosed with Bence Jones myeloma (BJMM) and nonsecretory myeloma (NSMM) by means of differential scanning calorimetry (DSC), serum protein electrophoresis, and free light chain assay. Specific alterations in the thermodynamic behavior of both BJMM and NSMM proteome have been revealed. On the basis of the transition temperature of the main transition in the calorimetric profiles and the shape similarity criterion, we defined BJMM and NSMM sets/subsets of thermograms with very similar thermodynamic features. We show that some of the BJMM and NSMM subsets correlate with previously defined secretory myeloma subsets (Todinova et al. Anal. Chem. 2011, 83, 7992). The established analogies strongly suggest that common molecular markers contribute to the calorimetric profiles of the different, secretory and nonsecretory, myeloma types; our data show robust evidence that these are ligands stabilizing the major serum proteins. We demonstrate that the DSC approach might be highly beneficial, especially for NSMM patients, since the characteristic modifications in the DSC profiles might serve as calorimetric markers when no monoclonal proteins can be detected in the bloodstream and the diagnosis heavily relies on invasive methods.

  9. Saccharomyces cerevisiae single-copy plasmids for auxotrophy compensation, multiple marker selection, and for designing metabolically cooperating communities

    PubMed Central

    Matsarskaia, Olga; Eckerstorfer, Florian; Ralser, Markus

    2016-01-01

    Auxotrophic markers are useful tools in cloning and genome editing, enable a large spectrum of genetic techniques, as well as facilitate the study of metabolite exchange interactions in microbial communities. If unused background auxotrophies are left uncomplemented however, yeast cells need to be grown in nutrient supplemented or rich growth media compositions, which precludes the analysis of biosynthetic metabolism, and which leads to a profound impact on physiology and gene expression. Here we present a series of 23 centromeric plasmids designed to restore prototrophy in typical Saccharomyces cerevisiae laboratory strains. The 23 single-copy plasmids complement for deficiencies in HIS3, LEU2, URA3, MET17 or LYS2 genes and in their combinations, to match the auxotrophic background of the popular functional-genomic yeast libraries that are based on the S288c strain. The plasmids are further suitable for designing self-establishing metabolically cooperating (SeMeCo) communities, and possess a uniform multiple cloning site to exploit multiple parallel selection markers in protein expression experiments. PMID:27830062

  10. Inhibition of DEPDC1A, a bad prognostic marker in multiple myeloma, delays growth and induces mature plasma cell markers in malignant plasma cells.

    PubMed

    Kassambara, Alboukadel; Schoenhals, Matthieu; Moreaux, Jérôme; Veyrune, Jean-Luc; Rème, Thierry; Goldschmidt, Hartmut; Hose, Dirk; Klein, Bernard

    2013-01-01

    High throughput DNA microarray has made it possible to outline genes whose expression in malignant plasma cells is associated with short overall survival of patients with Multiple Myeloma (MM). A further step is to elucidate the mechanisms encoded by these genes yielding to drug resistance and/or patients' short survival. We focus here on the biological role of the DEP (for Disheveled, EGL-10, Pleckstrin) domain contained protein 1A (DEPDC1A), a poorly known protein encoded by DEPDC1A gene, whose high expression in malignant plasma cells is associated with short survival of patients. Using conditional lentiviral vector delivery of DEPDC1A shRNA, we report that DEPDC1A knockdown delayed the growth of human myeloma cell lines (HMCLs), with a block in G2 phase of the cell cycle, p53 phosphorylation and stabilization, and p21(Cip1) accumulation. DEPDC1A knockdown also resulted in increased expression of mature plasma cell markers, including CXCR4, IL6-R and CD38. Thus DEPDC1A could contribute to the plasmablast features of MMCs found in some patients with adverse prognosis, blocking the differentiation of malignant plasma cells and promoting cell cycle.

  11. Discovery of Novel Disease-specific and Membrane-associated Candidate Markers in a Mouse Model of Multiple Sclerosis*

    PubMed Central

    Dagley, Laura F.; Croft, Nathan P.; Isserlin, Ruth; Olsen, Jonathan B.; Fong, Vincent; Emili, Andrew; Purcell, Anthony W.

    2014-01-01

    Multiple sclerosis is a chronic demyelinating disorder characterized by the infiltration of auto-reactive immune cells from the periphery into the central nervous system resulting in axonal injury and neuronal cell death. Experimental autoimmune encephalomyelitis represents the best characterized animal model as common clinical, histological, and immunological features are recapitulated. A label-free mass spectrometric proteomics approach was used to detect differences in protein abundance within specific fractions of disease-affected tissues including the soluble lysate derived from the spinal cord and membrane protein-enriched peripheral blood mononuclear cells. Tissues were harvested from actively induced experimental autoimmune encephalomyelitis mice and sham-induced (“vehicle” control) counterparts at the disease peak followed by subsequent analysis by nanoflow liquid chromatography tandem mass spectrometry. Relative protein quantitation was performed using both intensity- and fragmentation-based approaches. After statistical evaluation of the data, over 500 and 250 differentially abundant proteins were identified in the spinal cord and peripheral blood mononuclear cell data sets, respectively. More than half of these observations have not previously been linked to the disease. The biological significance of all candidate disease markers has been elucidated through rigorous literature searches, pathway analysis, and validation studies. Results from comprehensive targeted mass spectrometry analyses have confirmed the differential abundance of ∼200 candidate markers (≥twofold dysregulated expression) at a 70% success rate. This study is, to our knowledge, the first to examine the cell-surface proteome of peripheral blood mononuclear cells in experimental autoimmune encephalomyelitis. These data provide a unique mechanistic insight into the dynamics of peripheral immune cell infiltration into CNS-privileged sites at a molecular level and has identified

  12. The proteasome: mechanisms of biology and markers of activity and response to treatment in multiple myeloma.

    PubMed

    Manasanch, Elisabet E; Korde, Neha; Zingone, Adriana; Tageja, Nishant; Fernandez de Larrea, Carlos; Bhutani, Manisha; Wu, Peter; Roschewski, Mark; Landgren, Ola

    2014-08-01

    Since the early 1990s, the synthesis and subsequent clinical application of small molecule inhibitors of the ubiquitin proteasome pathway (UPP) has revolutionized the treatment and prognosis of multiple myeloma. In this review, we summarize important aspects of the biology of the UPP with a focus on its structure and key upstream/downstream regulatory components. We then review current knowledge of plasma cell sensitivity to proteasome inhibition and highlight new proteasome inhibitors that have recently entered clinical development. Lastly, we address the putative role of circulating proteasomes as a novel biomarker in multiple myeloma and provide guidance for future clinical trials using proteasome inhibitors.

  13. Endovascular treatment of chronic cerebro spinal venous insufficiency in patients with multiple sclerosis modifies circulating markers of endothelial dysfunction and coagulation activation: a prospective study.

    PubMed

    Napolitano, Mariasanta; Bruno, Aldo; Mastrangelo, Diego; De Vizia, Marcella; Bernardo, Benedetto; Rosa, Buonagura; De Lucia, Domenico

    2014-10-01

    We performed a monocentric observational prospective study to evaluate coagulation activation and endothelial dysfunction parameters in patients with multiple sclerosis undergoing endovascular treatment for cerebro-spinal-venous insufficiency. Between February 2011 and July 2012, 144 endovascular procedures in 110 patients with multiple sclerosis and chronical cerebro-spinal venous insufficiency were performed and they were prospectively analyzed. Each patient was included in the study according to previously published criteria, assessed by the investigators before enrollment. Endothelial dysfunction and coagulation activation parameters were determined before the procedure and during follow-up at 1, 3, 6, 9, 12, 15 and 18 months after treatment, respectively. After the endovascular procedure, patients were treated with standard therapies, with the addition of mesoglycan. Fifty-five percent of patients experienced a favorable outcome of multiple sclerosis within 1 month after treatment, 25% regressed in the following 3 months, 24.9% did not experience any benefit. In only 0.1% patients, acute recurrence was observed and it was treated with high-dose immunosuppressive therapy. No major complications were observed. Coagulation activation and endothelial dysfunction parameters were shown to be reduced at 1 month and stable up to 12-month follow-up, and they were furthermore associated with a good clinical outcome. Endovascular procedures performed by a qualified staff are well tolerated; they can be associated with other currently adopted treatments. Correlations between inflammation, coagulation activation and neurodegenerative disorders are here supported by the observed variations in plasma levels of markers of coagulation activation and endothelial dysfunction.

  14. Multiple markers of cortical morphology reveal evidence of supragranular thinning in schizophrenia

    PubMed Central

    Wagstyl, K; Ronan, L; Whitaker, K J; Goodyer, I M; Roberts, N; Crow, T J; Fletcher, P C

    2016-01-01

    In vivo structural neuroimaging can reliably identify changes to cortical morphology and its regional variation but cannot yet relate these changes to specific cortical layers. We propose, however, that by synthesizing principles of cortical organization, including relative contributions of different layers to sulcal and gyral thickness, regional patterns of variation in thickness of different layers across the cortical sheet and profiles of layer variation across functional hierarchies, it is possible to develop indirect morphological measures as markers of more specific cytoarchitectural changes. We developed four indirect measures sensitive to changes specifically occurring in supragranular cortical layers, and applied these to test the hypothesis that supragranular layers are disproportionately affected in schizophrenia. Our findings from the four different measures converge to indicate a predominance of supragranular thinning in schizophrenia, independent of medication and illness duration. We propose that these indirect measures offer novel ways of identifying layer-specific cortical changes, offering complementary in vivo observations to existing post-mortem studies. PMID:27070408

  15. Labeling of multiple cell markers and mRNA using automated apparatus.

    PubMed

    Paterson, Jennifer C; Ballabio, Erica; Mattsson, Göran; Turner, Susan H; Mason, David Y; Marafioti, Teresa

    2008-07-01

    Double immunoenzymatic labeling of 2 different molecules in tissue sections is a widely used technique. However, it is time consuming since the 2 immunoenzymatic procedures are carried out in sequence, and they must also be optimally performed to avoid unwanted background labeling. In this paper, we report that double immunoenzymatic staining performed using automated immunostaining apparatus considerably reduces the requirements in terms of time and is also highly reproducible and free of background. Three tissue markers can also be visualized by performing (after immunoperoxidase labeling) 2 sequential immuno-alkaline phosphatase procedures using different substrates. Furthermore, single or double detection of mRNA by in situ hybridization can be combined with immunoenzymatic labeling. Finally, automated labeling could also be performed on peripheral blood and bone marrow smears, opening the possibility of using this procedure in the analysis of hematologic/cytology samples.

  16. Minimal SNP overlap among multiple panels of ancestry informative markers argues for more international collaboration.

    PubMed

    Soundararajan, Usha; Yun, Libing; Shi, Meisen; Kidd, Kenneth K

    2016-07-01

    The century-old use of genetic markers to determine population relationships has morphed in modern forensics into use of markers to determine the ancestry of an individual from a DNA sample. Researchers have identified sets of SNPs that have frequency differences among populations and many sets of SNPs have been published for the purpose of inferring ancestry. Such inference also requires reference datasets for the particular set of SNPs selected. We have identified 21 largely independent published panels of ancestry informative SNPs (AISNPs) and examined their union of 1397 SNPs. No SNP occurs in more than 6 panels. The 1397 SNPs in 21 panels yield a largely empty matrix that is inhibiting progress on more refined ability to infer ancestry for a forensic sample. The most common set of reference populations is the HGDP set of 52 small population samples totaling a thousand individuals. Only 46 (3%) of the 1397 SNPs occur in three or more panels. We assembled a new dataset for 44 of those SNPs involving 4,559 individuals from 73 populations. Analyses of this dataset provided clear differentiation of only five biogeographic regions: sub-Saharan Africa, Europe and SW Asia, South Asia, East Asia, and the Americas. This is an inadequate level of biogeographic resolution already exceeded by other panels. We conclude that more such AISNP panels are not needed and that the forensic community must collaborate to develop a common set of highly differentiating AISNPs typed on a very large number of population samples. How that can be accomplished will be the subject of future discussion. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  17. The ROCK Inhibitor Y-27632 Improves Recovery of Human Embryonic Stem Cells after Fluorescence-Activated Cell Sorting with Multiple Cell Surface Markers

    PubMed Central

    Emre, Nil; Vidal, Jason G.; Elia, Jeanne; O'Connor, Eric D.; Paramban, Rosanto I.; Hefferan, Michael P.; Navarro, Roman; Goldberg, Danielle S.; Varki, Nissi M.; Marsala, Martin; Carson, Christian T.

    2010-01-01

    Background Due to the inherent sensitivity of human embryonic stem cells (hESCs) to manipulations, the recovery and survival of hESCs after fluorescence-activated cell sorting (FACS) can be low. Additionally, a well characterized and robust methodology for performing FACS on hESCs using multiple-cell surface markers has not been described. The p160-Rho-associated coiled kinase (ROCK) inhibitor, Y-27632, previously has been identified as enhancing survival of hESCs upon single-cell dissociation, as well as enhancing recovery from cryopreservation. Here we examined the application of Y-27632 to hESCs after FACS to improve survival in both feeder-dependent and feeder-independent growth conditions. Methodology/Principal Findings HESCs were sorted using markers for SSEA-3, TRA-1-81, and SSEA-1. Cells were plated after sorting for 24 hours in either the presence or the absence of Y-27632. In both feeder-dependent and feeder-independent conditions, cell survival was greater when Y-27632 was applied to the hESCs after sort. Specifically, treatment of cells with Y-27632 improved post-sort recovery up to four fold. To determine the long-term effects of sorting with and without the application of Y-27632, hESCs were further analyzed. Specifically, hESCs sorted with and without the addition of Y-27632 retained normal morphology, expressed hESC-specific markers as measured by immunocytochemistry and flow cytometry, and maintained a stable karyotype. In addition, the hESCs could differentiate into three germ layers in vitro and in vivo in both feeder-dependent and feeder-independent growth conditions. Conclusions/Significance The application of Y-27632 to hESCs after cell sorting improves cell recovery with no observed effect on pluripotency, and enables the consistent recovery of hESCs by FACS using multiple surface markers. This improved methodology for cell sorting of hESCs will aid many applications such as removal of hESCs from secondary cell types, identification and

  18. The Longue Durée of Genetic Ancestry: Multiple Genetic Marker Systems and Celtic Origins on the Atlantic Facade of Europe

    PubMed Central

    McEvoy, Brian; Richards, Martin; Forster, Peter; Bradley, Daniel G.

    2004-01-01

    Celtic languages are now spoken only on the Atlantic facade of Europe, mainly in Britain and Ireland, but were spoken more widely in western and central Europe until the collapse of the Roman Empire in the first millennium a.d. It has been common to couple archaeological evidence for the expansion of Iron Age elites in central Europe with the dispersal of these languages and of Celtic ethnicity and to posit a central European “homeland” for the Celtic peoples. More recently, however, archaeologists have questioned this “migrationist” view of Celtic ethnogenesis. The proposition of a central European ancestry should be testable by examining the distribution of genetic markers; however, although Y-chromosome patterns in Atlantic Europe show little evidence of central European influence, there has hitherto been insufficient data to confirm this by use of mitochondrial DNA (mtDNA). Here, we present both new mtDNA data from Ireland and a novel analysis of a greatly enlarged European mtDNA database. We show that mtDNA lineages, when analyzed in sufficiently large numbers, display patterns significantly similar to a large fraction of both Y-chromosome and autosomal variation. These multiple genetic marker systems indicate a shared ancestry throughout the Atlantic zone, from northern Iberia to western Scandinavia, that dates back to the end of the last Ice Age. PMID:15309688

  19. Evidence of multiple paternity in Morelet's Crocodile (Crocodylus moreletii) in Belize, CA, inferred from microsatellite markers.

    PubMed

    McVay, John D; Rodriguez, David; Rainwater, Thomas R; Dever, Jennifer A; Platt, Steven G; McMurry, Scott T; Forstner, Michael R J; Densmore, Llewellyn D

    2008-12-01

    Microsatellite data were generated from hatchlings collected from ten nests of Morelet's Crocodile (Crocodylus moreletii) from New River Lagoon and Gold Button Lagoon in Belize to test for evidence of multiple paternity. Nine microsatellite loci were genotyped for 188 individuals from the 10 nests, alongside 42 nonhatchlings from Gold Button Lagoon. Then mitochondrial control region sequences were generated for the nonhatchlings and for one individual from each nest to test for presence of C. acutus-like haplotypes. Analyses of five of the nine microsatellite loci revealed evidence that progeny from five of the ten nests were sired by at least two males. These data suggest the presence of multiple paternity as a mating strategy in the true crocodiles. This information may be useful in the application of conservation and management techniques to the 12 species in this genus, most of which are threatened or endangered.

  20. Development of Multiple Polymorphic Microsatellite Markers for Ceratina calcarata (Hymenoptera: Apidae) Using Genome-Wide Analysis.

    PubMed

    Shell, Wyatt A; Rehan, Sandra M

    2016-01-01

    The small carpenter bee, Ceratina calcarata (Robertson), is a widespread native pollinator across eastern North America. The behavioral ecology and nesting biology of C. calcarata has been relatively well-studied and the species is emerging as a model organism for both native pollinator and social evolution research. C. calcarata is subsocial: reproductively mature females provide extended maternal care to their brood. As such, studies of C. calcarata may also reveal patterns of relatedness and demography unique to primitively social Hymenoptera. Here, we present 21 microsatellite loci, isolated from the recently completed C. calcarata genome. Screening in 39 individuals across their distribution revealed that no loci were in linkage disequilibrium, nor did any deviate significantly from Hardy-Weinberg following sequential Bonferroni correction. Allele count ranged from 2 to 14, and observed and expected heterozygosities ranged from 0.08 to 0.82 (mean 0.47) and 0.26 to 0.88 (mean 0.56), respectively. These markers will enable studies of population-wide genetic structuring across C. calcarata's distribution. Such tools will also allow for exploration of between and within-colony relatedness in this subsocial native pollinator.

  1. Development of Multiple Polymorphic Microsatellite Markers for Ceratina calcarata (Hymenoptera: Apidae) Using Genome-Wide Analysis

    PubMed Central

    Shell, Wyatt A.; Rehan, Sandra M.

    2016-01-01

    The small carpenter bee, Ceratina calcarata (Robertson), is a widespread native pollinator across eastern North America. The behavioral ecology and nesting biology of C. calcarata has been relatively well-studied and the species is emerging as a model organism for both native pollinator and social evolution research. C. calcarata is subsocial: reproductively mature females provide extended maternal care to their brood. As such, studies of C. calcarata may also reveal patterns of relatedness and demography unique to primitively social Hymenoptera. Here, we present 21 microsatellite loci, isolated from the recently completed C. calcarata genome. Screening in 39 individuals across their distribution revealed that no loci were in linkage disequilibrium, nor did any deviate significantly from Hardy-Weinberg following sequential Bonferroni correction. Allele count ranged from 2 to 14, and observed and expected heterozygosities ranged from 0.08 to 0.82 (mean 0.47) and 0.26 to 0.88 (mean 0.56), respectively. These markers will enable studies of population-wide genetic structuring across C. calcarata’s distribution. Such tools will also allow for exploration of between and within-colony relatedness in this subsocial native pollinator. PMID:27324584

  2. Multiple exocytotic markers accumulate at the sites of perifungal membrane biogenesis in arbuscular mycorrhizas.

    PubMed

    Genre, A; Ivanov, S; Fendrych, M; Faccio, A; Zársky, V; Bisseling, T; Bonfante, P

    2012-01-01

    Arbuscular mycorrhizas (AMs) are symbiotic interactions established within the roots of most plants by soil fungi belonging to the Glomeromycota. The extensive accommodation of the fungus in the root tissues largely takes place intracellularly, within a specialized interface compartment surrounded by the so-called perifungal membrane, an extension of the host plasmalemma. By combining live confocal imaging of green fluorescent protein (GFP)-tagged proteins and transmission electron microscopy (TEM), we have investigated the mechanisms leading to the biogenesis of this membrane. Our results show that pre-penetration responses and symbiotic interface construction are associated with extensive membrane dynamics. They involve the main components of the exocytotic machinery, with a major participation of the Golgi apparatus, as revealed by both TEM and in vivo GFP imaging. The labeling of known exocytosis markers, such as v-SNARE proteins of the VAMP72 family and the EXO84b subunit of the exocyst complex, allowed live imaging of the cell components involved in perifungal membrane construction, clarifying how this takes place ahead of the growing intracellular hypha. Lastly, our novel data are used to illustrate a model of membrane dynamics within the pre-penetration apparatus during AM fungal penetration.

  3. Occupational attainment as a marker of cognitive reserve in multiple sclerosis.

    PubMed

    Ghaffar, Omar; Fiati, Marty; Feinstein, Anthony

    2012-01-01

    Cognitive dysfunction affects half of MS patients. Although brain atrophy generally yields the most robust MRI correlations with cognition, significant variance in cognition between individual MS patients remains unexplained. Recently, markers of cognitive reserve such as premorbid intelligence have emerged as important predictors of neuropsychological performance in MS. In the present study, we aimed to extend the cognitive reserve construct by examining the potential contribution of occupational attainment to cognitive decline in MS patients. Brain atrophy, estimated premorbid IQ, and occupational attainment were assessed in 72 MS patients. The Minimal Assessment of Cognitive Functioning in MS was used to evaluate indices of information processing speed, memory, and executive function. Results showed that occupational attainment was a significant predictor of information processing speed, memory, and executive function in hierarchical linear regressions after accounting for brain atrophy and premorbid IQ. These data suggest that MS patients with low occupational attainment fare worse cognitively than those with high occupational attainment after controlling for brain atrophy and premorbid IQ. Occupation, like premorbid IQ, therefore may make an independent contribution to cognitive outcome in MS. Information regarding an individual's occupation is easily acquired and may serve as a useful proxy for cognitive reserve in clinical settings.

  4. Relationships among pest flour beetles of the genus Tribolium (Tenebrionidae) inferred from multiple molecular markers

    PubMed Central

    Angelini, David R.; Jockusch, Elizabeth L.

    2008-01-01

    Model species often provide initial hypotheses and tools for studies of development, genetics, and molecular evolution in closely related species. Flour beetles of the genus Tribolium MacLeay (1825) are one group with potential for such comparative studies. Tribolium castaneum (Herbst 1797) is an increasingly useful developmental genetic system. The convenience with which congeneric and other species of tenebrionid flour beetles can be reared in the laboratory makes this group attractive for comparative studies on a small phylogenetic scale. Here we present the results of phylogenetic analyses of relationships among the major pest species of Tribolium based on two mitochondrial and three nuclear markers (cytochrome oxidase 1, 16S ribosomal DNA, wingless, 28S ribosomal DNA, histone H3). The utility of partitioning the dataset in a manner informed by biological structure and function is demonstrated by comparing various partitioning strategies. In parsimony and partitioned Bayesian analyses of the combined dataset, the castaneum and confusum species groups are supported as monophyletic and as each other’s closest relatives. However, a sister group relationship between this clade and Tribolium brevicornis (Leconte 1859) is not supported. Therefore, we suggest transferring brevicornis group species to the genus Aphanotus Leconte (1862). The inferred phylogeny provides an evolutionary framework for comparative studies using flour beetles. PMID:18024090

  5. Relationships among pest flour beetles of the genus Tribolium (Tenebrionidae) inferred from multiple molecular markers.

    PubMed

    Angelini, David R; Jockusch, Elizabeth L

    2008-01-01

    Model species often provide initial hypotheses and tools for studies of development, genetics and molecular evolution in closely related species. Flour beetles of the genus Tribolium Macleay (1825) are one group with potential for such comparative studies. Tribolium castaneum (Herbst 1797) is an increasingly useful developmental genetic system. The convenience with which congeneric and other species of tenebrionid flour beetles can be reared in the laboratory makes this group attractive for comparative studies on a small phylogenetic scale. Here we present the results of phylogenetic analyses of relationships among the major pest species of Tribolium based on two mitochondrial and three nuclear markers (cytochrome oxidase 1, 16S ribosomal DNA, wingless, 28S ribosomal DNA and histone H3). The utility of partitioning the dataset in a manner informed by biological structure and function is demonstrated by comparing various partitioning strategies. In parsimony and partitioned Bayesian analyses of the combined dataset, the castaneum and confusum species groups are supported as monophyletic and as each other's closest relatives. However, a sister group relationship between this clade and Tribolium brevicornis (Leconte 1859) is not supported. The inferred phylogeny provides an evolutionary framework for comparative studies using flour beetles.

  6. Selection of a marker gene to construct a reference library for wetland plants, and the application of metabarcoding to analyze the diet of wintering herbivorous waterbirds

    PubMed Central

    Yang, Yuzhan; Zhan, Aibin; Meng, Fanjuan; Xu, Wenbin

    2016-01-01

    Food availability and diet selection are important factors influencing the abundance and distribution of wild waterbirds. In order to better understand changes in waterbird population, it is essential to figure out what they feed on. However, analyzing their diet could be difficult and inefficient using traditional methods such as microhistologic observation. Here, we addressed this gap of knowledge by investigating the diet of greater white-fronted goose Anser albifrons and bean goose Anser fabalis, which are obligate herbivores wintering in China, mostly in the Middle and Lower Yangtze River floodplain. First, we selected a suitable and high-resolution marker gene for wetland plants that these geese would consume during the wintering period. Eight candidate genes were included: rbcL, rpoC1, rpoB, matK, trnH-psbA, trnL (UAA), atpF-atpH, and psbK-psbI. The selection was performed via analysis of representative sequences from NCBI and comparison of amplification efficiency and resolution power of plant samples collected from the wintering area. The trnL gene was chosen at last with c/h primers, and a local plant reference library was constructed with this gene. Then, utilizing DNA metabarcoding, we discovered 15 food items in total from the feces of these birds. Of the 15 unique dietary sequences, 10 could be identified at specie level. As for greater white-fronted goose, 73% of sequences belonged to Poaceae spp., and 26% belonged to Carex spp. In contrast, almost all sequences of bean goose belonged to Carex spp. (99%). Using the same samples, microhistology provided consistent food composition with metabarcoding results for greater white-fronted goose, while 13% of Poaceae was recovered for bean goose. In addition, two other taxa were discovered only through microhistologic analysis. Although most of the identified taxa matched relatively well between the two methods, DNA metabarcoding gave taxonomically more detailed information. Discrepancies were likely due to

  7. Selection of a marker gene to construct a reference library for wetland plants, and the application of metabarcoding to analyze the diet of wintering herbivorous waterbirds.

    PubMed

    Yang, Yuzhan; Zhan, Aibin; Cao, Lei; Meng, Fanjuan; Xu, Wenbin

    2016-01-01

    Food availability and diet selection are important factors influencing the abundance and distribution of wild waterbirds. In order to better understand changes in waterbird population, it is essential to figure out what they feed on. However, analyzing their diet could be difficult and inefficient using traditional methods such as microhistologic observation. Here, we addressed this gap of knowledge by investigating the diet of greater white-fronted goose Anser albifrons and bean goose Anser fabalis, which are obligate herbivores wintering in China, mostly in the Middle and Lower Yangtze River floodplain. First, we selected a suitable and high-resolution marker gene for wetland plants that these geese would consume during the wintering period. Eight candidate genes were included: rbcL, rpoC1, rpoB, matK, trnH-psbA, trnL (UAA), atpF-atpH, and psbK-psbI. The selection was performed via analysis of representative sequences from NCBI and comparison of amplification efficiency and resolution power of plant samples collected from the wintering area. The trnL gene was chosen at last with c/h primers, and a local plant reference library was constructed with this gene. Then, utilizing DNA metabarcoding, we discovered 15 food items in total from the feces of these birds. Of the 15 unique dietary sequences, 10 could be identified at specie level. As for greater white-fronted goose, 73% of sequences belonged to Poaceae spp., and 26% belonged to Carex spp. In contrast, almost all sequences of bean goose belonged to Carex spp. (99%). Using the same samples, microhistology provided consistent food composition with metabarcoding results for greater white-fronted goose, while 13% of Poaceae was recovered for bean goose. In addition, two other taxa were discovered only through microhistologic analysis. Although most of the identified taxa matched relatively well between the two methods, DNA metabarcoding gave taxonomically more detailed information. Discrepancies were likely due to

  8. Multiple immune deviations predictive for IVF failure as possible markers for IVIG therapy.

    PubMed

    Chernyshov, Viktor P; Dons'koi, Boris V; Sudoma, Iryna O; Goncharova, Yana O

    2016-08-01

    Recently we have shown that immune deviations (ID) may predict IVF failure. Benefit from IVIG therapy was observed in 115 women with repeated IVF failure according to proposed multiple ID that appeared unfavorable for implantation and live birth. Group of 123 women with repeated IVF failure without IVIG therapy was compared with former group. Immune phenotype and NK activity of peripheral blood lymphocytes were studied by flow cytometry. Potentially predictive for IVF failure ID included elevated expression of CD56, CD158a in T lymphocytes, decreased levels of CD4T lymphocytes, up-regulated expression of HLA DR in CD8+ T cells and NK cells, elevated number of NK cells and increased NK cytotoxicity, increased or decreased expression of CD158a and CD8 in NK cells. Three or more ID may predict implantation failure to a greater degree than one or two ID. In women receiving IVIG in subgroups with 0-1 and 2 ID, there was no increase in implantation rate (IR) and live birth rate (LBR) after IVIG in comparison with patients with the same number of ID but without IVIG correction. After IVIG therapy decreased IR and LBR were restored in women with three or more immune deviations. Multiple immune deviations indicate IVF patients who may benefit from IVIG therapy. IVIG seems to convert "unfavorable" immune phenotype to "favorable" one.

  9. Numerical simulation of drop impact on a liquid-liquid interface with a multiple marker front-capturing method

    NASA Astrophysics Data System (ADS)

    Coyajee, Emil; Boersma, Bendiks Jan

    2009-07-01

    The gravity-driven motion of a droplet impacting on a liquid-liquid interface is studied. The full Navier-Stokes equations are solved on a fixed, uniform grid using a finite difference/front-capturing method. For the representation of fluid-fluid interfaces, a coupled Level-Set/Volume-Of-Fluid method [M. Sussman, E.G. Puckett, A coupled Level-Set and Volume-of-Fluid method for computing 3D and axisymmetric incompressible two-phase flows, J. Comp. Phys. 162 (2000) 301-337] is used, in which we introduce the novel approach of describing separate interfaces with different marker functions. As a consequence, we prevent numerical coalescence of the droplet and the liquid-liquid interface without excessive (local) grid refinement. To validate our method, numerical simulations of the drop impact event are compared with experiments [Z. Mohamed-Kassim, E.K. Longmire, Drop impact on a liquid-liquid interface, Phys. Fluids 15 (2003) 3263-3273]. Furthermore, a comparison is made with the numerical results of [A. Esmaeeli, G. Tryggvason, Direct numerical simulations of bubbly flows. Part 2. Moderate Reynolds number arrays, J. Fluid Mech. 385 (1999) 325-358] for an array of rising bubbles. The investigation shows that the multiple marker approach successfully prevents numerical coalescence of interfaces and adequately captures the effect of surface tension.

  10. Revisiting the phylogeography and demography of European badgers (Meles meles) based on broad sampling, multiple markers and simulations.

    PubMed

    Frantz, A C; McDevitt, A D; Pope, L C; Kochan, J; Davison, J; Clements, C F; Elmeros, M; Molina-Vacas, G; Ruiz-Gonzalez, A; Balestrieri, A; Van Den Berge, K; Breyne, P; Do Linh San, E; Agren, E O; Suchentrunk, F; Schley, L; Kowalczyk, R; Kostka, B I; Cirović, D; Sprem, N; Colyn, M; Ghirardi, M; Racheva, V; Braun, C; Oliveira, R; Lanszki, J; Stubbe, A; Stubbe, M; Stier, N; Burke, T

    2014-11-01

    Although the phylogeography of European mammals has been extensively investigated since the 1990s, many studies were limited in terms of sampling distribution, the number of molecular markers used and the analytical techniques employed, frequently leading to incomplete postglacial recolonisation scenarios. The broad-scale genetic structure of the European badger (Meles meles) is of interest as it may result from historic restriction to glacial refugia and/or recent anthropogenic impact. However, previous studies were based mostly on samples from western Europe, making it difficult to draw robust conclusions about the location of refugia, patterns of postglacial expansion and recent demography. In the present study, continent-wide sampling and analyses with multiple markers provided evidence for two glacial refugia (Iberia and southeast Europe) that contributed to the genetic variation observed in badgers in Europe today. Approximate Bayesian computation provided support for a colonisation of Scandinavia from both Iberian and southeastern refugia. In the whole of Europe, we observed a decline in genetic diversity with increasing latitude, suggesting that the reduced diversity in the peripheral populations resulted from a postglacial expansion processes. Although MSVAR v.1.3 also provided evidence for recent genetic bottlenecks in some of these peripheral populations, the simulations performed to estimate the method's power to correctly infer the past demography of our empirical populations suggested that the timing and severity of bottlenecks could not be established with certainty. We urge caution against trying to relate demographic declines inferred using MSVAR with particular historic or climatological events.

  11. Genotype-Based Bayesian Analysis of Gene-Environment Interactions with Multiple Genetic Markers and Misclassification in Environmental Factors

    PubMed Central

    Lobach, Iryna; Fan, Ruzong

    2015-01-01

    A key component to understanding etiology of complex diseases, such as cancer, diabetes, alcohol dependence, is to investigate gene-environment interactions. This work is motivated by the following two concerns in the analysis of gene-environment interactions. First, multiple genetic markers in moderate linkage disequilibrium may be involved in susceptibility to a complex disease. Second, environmental factors may be subject to misclassification. We develop a genotype based Bayesian pseudolikelihood approach that accommodates linkage disequilibrium in genetic markers and misclassification in environmental factors. Since our approach is genotype based, it allows the observed genetic information to enter the model directly thus eliminating the need to infer haplotype phase and simplifying computations. Bayesian approach allows shrinking parameter estimates towards prior distribution to improve estimation and inference when environmental factors are subject to misclassification. Simulation experiments demonstrated that our method produced parameter estimates that are nearly unbiased even for small sample sizes. An application of our method is illustrated using a case-control study of interaction between early onset of drinking and genes involved in dopamine pathway. PMID:26180529

  12. Genotype-Based Bayesian Analysis of Gene-Environment Interactions with Multiple Genetic Markers and Misclassification in Environmental Factors.

    PubMed

    Lobach, Iryna; Fan, Ruzong

    A key component to understanding etiology of complex diseases, such as cancer, diabetes, alcohol dependence, is to investigate gene-environment interactions. This work is motivated by the following two concerns in the analysis of gene-environment interactions. First, multiple genetic markers in moderate linkage disequilibrium may be involved in susceptibility to a complex disease. Second, environmental factors may be subject to misclassification. We develop a genotype based Bayesian pseudolikelihood approach that accommodates linkage disequilibrium in genetic markers and misclassification in environmental factors. Since our approach is genotype based, it allows the observed genetic information to enter the model directly thus eliminating the need to infer haplotype phase and simplifying computations. Bayesian approach allows shrinking parameter estimates towards prior distribution to improve estimation and inference when environmental factors are subject to misclassification. Simulation experiments demonstrated that our method produced parameter estimates that are nearly unbiased even for small sample sizes. An application of our method is illustrated using a case-control study of interaction between early onset of drinking and genes involved in dopamine pathway.

  13. Transcriptome profiling in response to different types of ionizing radiation and identification of multiple radio marker genes in rice.

    PubMed

    Hwang, Jung Eun; Hwang, Sun-Goo; Kim, Sun-Hee; Lee, Kyung Jun; Jang, Cheol Seong; Kim, Jin-Baek; Kim, Sang Hoon; Ha, Bo-Keun; Ahn, Joon-Woo; Kang, Si-Yong; Kim, Dong Sub

    2014-04-01

    Ionizing radiation (IR) affects gene expression from plant genomes. To monitor the genome-wide transcriptional changes induced by three types of IR, we used the rice Affymetrix GeneChip microarray to identify genes that are up- or down-regulated by gamma rays (GAs), cosmic rays (CRs) and ion beams (IBs). The overall expression patterns in rice seedlings generated from seeds exposed to GAs and IBs were similar but differed for CRs exposure. Expression profiles of genes involved in metabolic pathways and cellular response were identified using MapMan analysis. This result revealed that IRs induced gene expression related to sucrose-starch metabolisms; sugar and starch accumulation was significantly increased in response to three types of IR in rice. In addition, we compared the genes commonly up- or down-regulated by exposure to three types of IR and identified 53 candidate radio marker genes (RMGs) that were differentially regulated by radiation exposure but not by other stresses. Among these genes, we selected six RMGs commonly applicable to different types of IR by specific coexpression networks using the algorithm for the reconstruction of accurate cellular networks (aracne) and confirmed the expression of these genes by reverse transcription-polymerase chain reaction (RT-PCR) analysis. Our results provided insight into the mechanisms of the responses to different types of IR and identified multiple marker genes to predict sensitivity to three types of IR. © 2013 Scandinavian Plant Physiology Society.

  14. Revisiting the phylogeography and demography of European badgers (Meles meles) based on broad sampling, multiple markers and simulations

    PubMed Central

    Frantz, A C; McDevitt, A D; Pope, L C; Kochan, J; Davison, J; Clements, C F; Elmeros, M; Molina-Vacas, G; Ruiz-Gonzalez, A; Balestrieri, A; Van Den Berge, K; Breyne, P; Do Linh San, E; Ågren, E O; Suchentrunk, F; Schley, L; Kowalczyk, R; Kostka, B I; Ćirović, D; Šprem, N; Colyn, M; Ghirardi, M; Racheva, V; Braun, C; Oliveira, R; Lanszki, J; Stubbe, A; Stubbe, M; Stier, N; Burke, T

    2014-01-01

    Although the phylogeography of European mammals has been extensively investigated since the 1990s, many studies were limited in terms of sampling distribution, the number of molecular markers used and the analytical techniques employed, frequently leading to incomplete postglacial recolonisation scenarios. The broad-scale genetic structure of the European badger (Meles meles) is of interest as it may result from historic restriction to glacial refugia and/or recent anthropogenic impact. However, previous studies were based mostly on samples from western Europe, making it difficult to draw robust conclusions about the location of refugia, patterns of postglacial expansion and recent demography. In the present study, continent-wide sampling and analyses with multiple markers provided evidence for two glacial refugia (Iberia and southeast Europe) that contributed to the genetic variation observed in badgers in Europe today. Approximate Bayesian computation provided support for a colonisation of Scandinavia from both Iberian and southeastern refugia. In the whole of Europe, we observed a decline in genetic diversity with increasing latitude, suggesting that the reduced diversity in the peripheral populations resulted from a postglacial expansion processes. Although MSVAR v.1.3 also provided evidence for recent genetic bottlenecks in some of these peripheral populations, the simulations performed to estimate the method's power to correctly infer the past demography of our empirical populations suggested that the timing and severity of bottlenecks could not be established with certainty. We urge caution against trying to relate demographic declines inferred using MSVAR with particular historic or climatological events. PMID:24781805

  15. Investigation of cerebral microbleeds in multiple sclerosis as a potential marker of blood-brain barrier dysfunction.

    PubMed

    Eisele, Philipp; Alonso, Angelika; Griebe, Martin; Szabo, Kristina; Hennerici, Michael G; Gass, Achim

    2016-05-01

    In multiple sclerosis (MS) lesions blood-brain-barrier (BBB) breakdown is a common phenomenon delineating the phase of focal inflammation in developing MS lesions. In other pathologies like cerebral amyloid angiopathy or arteriosclerotic cerebral small vessel disease permanent cerebral microbleeds (CMB) have been shown to be sensitive markers indicating BBB dysfunction. We were interested in the potential role of T(2)*-weighted MRI and CMBs as BBB integrity markers in MS. A large cohort of 189 MS patients (179 relapsing remitting MS and 10 secondary progressive MS) was investigated on a 3T MRI system with conventional and T(2)*-weighted gradient echo MRI (T(2)*w) sequences. T(2)*w images were analysed for CMBs by experienced raters. None of the MS patients showed a CMB. On T(2)*w MRI the prevalence of CMBs is not higher in MS patients than what is to be expected in young healthy people. In contrast to pathologies with structural vascular changes like small vessel disease or cerebral amyloid angiopathy, CMBs are not seen in MS where the immune reaction is causing a functional change in the BBB. Copyright © 2016. Published by Elsevier B.V.

  16. A genome-wide screen for promoter methylation in lung cancer identifies novel methylation markers for multiple malignancies.

    PubMed

    Shames, David S; Girard, Luc; Gao, Boning; Sato, Mitsuo; Lewis, Cheryl M; Shivapurkar, Narayan; Jiang, Aixiang; Perou, Charles M; Kim, Young H; Pollack, Jonathan R; Fong, Kwun M; Lam, Chi-Leung; Wong, Maria; Shyr, Yu; Nanda, Rita; Olopade, Olufunmilayo I; Gerald, William; Euhus, David M; Shay, Jerry W; Gazdar, Adi F; Minna, John D

    2006-12-01

    Promoter hypermethylation coupled with loss of heterozygosity at the same locus results in loss of gene function in many tumor cells. The "rules" governing which genes are methylated during the pathogenesis of individual cancers, how specific methylation profiles are initially established, or what determines tumor type-specific methylation are unknown. However, DNA methylation markers that are highly specific and sensitive for common tumors would be useful for the early detection of cancer, and those required for the malignant phenotype would identify pathways important as therapeutic targets. In an effort to identify new cancer-specific methylation markers, we employed a high-throughput global expression profiling approach in lung cancer cells. We identified 132 genes that have 5' CpG islands, are induced from undetectable levels by 5-aza-2'-deoxycytidine in multiple non-small cell lung cancer cell lines, and are expressed in immortalized human bronchial epithelial cells. As expected, these genes were also expressed in normal lung, but often not in companion primary lung cancers. Methylation analysis of a subset (45/132) of these promoter regions in primary lung cancer (n = 20) and adjacent nonmalignant tissue (n = 20) showed that 31 genes had acquired methylation in the tumors, but did not show methylation in normal lung or peripheral blood cells. We studied the eight most frequently and specifically methylated genes from our lung cancer dataset in breast cancer (n = 37), colon cancer (n = 24), and prostate cancer (n = 24) along with counterpart nonmalignant tissues. We found that seven loci were frequently methylated in both breast and lung cancers, with four showing extensive methylation in all four epithelial tumors. By using a systematic biological screen we identified multiple genes that are methylated with high penetrance in primary lung, breast, colon, and prostate cancers. The cross-tumor methylation pattern we observed for these novel markers suggests

  17. A Genome-Wide Screen for Promoter Methylation in Lung Cancer Identifies Novel Methylation Markers for Multiple Malignancies

    PubMed Central

    Shames, David S; Girard, Luc; Gao, Boning; Sato, Mitsuo; Lewis, Cheryl M; Shivapurkar, Narayan; Jiang, Aixiang; Perou, Charles M; Kim, Young H; Pollack, Jonathan R; Fong, Kwun M; Lam, Chi-Leung; Wong, Maria; Shyr, Yu; Nanda, Rita; Olopade, Olufunmilayo I; Gerald, William; Euhus, David M; Shay, Jerry W; Gazdar, Adi F; Minna, John D

    2006-01-01

    Background Promoter hypermethylation coupled with loss of heterozygosity at the same locus results in loss of gene function in many tumor cells. The “rules” governing which genes are methylated during the pathogenesis of individual cancers, how specific methylation profiles are initially established, or what determines tumor type-specific methylation are unknown. However, DNA methylation markers that are highly specific and sensitive for common tumors would be useful for the early detection of cancer, and those required for the malignant phenotype would identify pathways important as therapeutic targets. Methods and Findings In an effort to identify new cancer-specific methylation markers, we employed a high-throughput global expression profiling approach in lung cancer cells. We identified 132 genes that have 5′ CpG islands, are induced from undetectable levels by 5-aza-2′-deoxycytidine in multiple non-small cell lung cancer cell lines, and are expressed in immortalized human bronchial epithelial cells. As expected, these genes were also expressed in normal lung, but often not in companion primary lung cancers. Methylation analysis of a subset (45/132) of these promoter regions in primary lung cancer (n = 20) and adjacent nonmalignant tissue (n = 20) showed that 31 genes had acquired methylation in the tumors, but did not show methylation in normal lung or peripheral blood cells. We studied the eight most frequently and specifically methylated genes from our lung cancer dataset in breast cancer (n = 37), colon cancer (n = 24), and prostate cancer (n = 24) along with counterpart nonmalignant tissues. We found that seven loci were frequently methylated in both breast and lung cancers, with four showing extensive methylation in all four epithelial tumors. Conclusions By using a systematic biological screen we identified multiple genes that are methylated with high penetrance in primary lung, breast, colon, and prostate cancers. The cross-tumor methylation

  18. Multiple SNP Markers Reveal Fine-Scale Population and Deep Phylogeographic Structure in European Anchovy (Engraulis encrasicolus L.)

    PubMed Central

    Zarraonaindia, Iratxe; Iriondo, Mikel; Albaina, Aitor; Pardo, Miguel Angel; Manzano, Carmen; Grant, W. Stewart; Irigoien, Xabier; Estonba, Andone

    2012-01-01

    Geographic surveys of allozymes, microsatellites, nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) have detected several genetic subdivisions among European anchovy populations. However, these studies have been limited in their power to detect some aspects of population structure by the use of a single or a few molecular markers, or by limited geographic sampling. We use a multi-marker approach, 47 nDNA and 15 mtDNA single nucleotide polymorphisms (SNPs), to analyze 626 European anchovies from the whole range of the species to resolve shallow and deep levels of population structure. Nuclear SNPs define 10 genetic entities within two larger genetically distinctive groups associated with oceanic variables and different life-history traits. MtDNA SNPs define two deep phylogroups that reflect ancient dispersals and colonizations. These markers define two ecological groups. One major group of Iberian-Atlantic populations is associated with upwelling areas on narrow continental shelves and includes populations spawning and overwintering in coastal areas. A second major group includes northern populations in the North East (NE) Atlantic (including the Bay of Biscay) and the Mediterranean and is associated with wide continental shelves with local larval retention currents. This group tends to spawn and overwinter in oceanic areas. These two groups encompass ten populations that differ from previously defined management stocks in the Alboran Sea, Iberian-Atlantic and Bay of Biscay regions. In addition, a new North Sea-English Channel stock is defined. SNPs indicate that some populations in the Bay of Biscay are genetically closer to North Western (NW) Mediterranean populations than to other populations in the NE Atlantic, likely due to colonizations of the Bay of Biscay and NW Mediterranean by migrants from a common ancestral population. Northern NE Atlantic populations were subsequently established by migrants from the Bay of Biscay. Populations along the Iberian

  19. Multiple SNP markers reveal fine-scale population and deep phylogeographic structure in European anchovy (Engraulis encrasicolus L.).

    PubMed

    Zarraonaindia, Iratxe; Iriondo, Mikel; Albaina, Aitor; Pardo, Miguel Angel; Manzano, Carmen; Grant, W Stewart; Irigoien, Xabier; Estonba, Andone

    2012-01-01

    Geographic surveys of allozymes, microsatellites, nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) have detected several genetic subdivisions among European anchovy populations. However, these studies have been limited in their power to detect some aspects of population structure by the use of a single or a few molecular markers, or by limited geographic sampling. We use a multi-marker approach, 47 nDNA and 15 mtDNA single nucleotide polymorphisms (SNPs), to analyze 626 European anchovies from the whole range of the species to resolve shallow and deep levels of population structure. Nuclear SNPs define 10 genetic entities within two larger genetically distinctive groups associated with oceanic variables and different life-history traits. MtDNA SNPs define two deep phylogroups that reflect ancient dispersals and colonizations. These markers define two ecological groups. One major group of Iberian-Atlantic populations is associated with upwelling areas on narrow continental shelves and includes populations spawning and overwintering in coastal areas. A second major group includes northern populations in the North East (NE) Atlantic (including the Bay of Biscay) and the Mediterranean and is associated with wide continental shelves with local larval retention currents. This group tends to spawn and overwinter in oceanic areas. These two groups encompass ten populations that differ from previously defined management stocks in the Alboran Sea, Iberian-Atlantic and Bay of Biscay regions. In addition, a new North Sea-English Channel stock is defined. SNPs indicate that some populations in the Bay of Biscay are genetically closer to North Western (NW) Mediterranean populations than to other populations in the NE Atlantic, likely due to colonizations of the Bay of Biscay and NW Mediterranean by migrants from a common ancestral population. Northern NE Atlantic populations were subsequently established by migrants from the Bay of Biscay. Populations along the Iberian

  20. Impaired heart rate variability as a marker of cardiovascular autonomic dysfunction in multiple sclerosis.

    PubMed

    Tombul, Temel; Anlar, Omer; Tuncer, Mustafa; Huseyinoglu, Nergis; Eryonucu, Beyhan

    2011-06-01

    Multiple sclerosis (MS) can cause alterations in autonomic cardiovascular functions. We aimed to investigate the correlation of disease activity and disability with heart rate variability (HRV) of cardiovascular autonomic dysfunction (CAD) demonstrated by 24-h Holter monitorization. Thirty-four patients with clinically active relapsing-remitting MS, age 33.8 +/- 7.6 years, were studied. Twenty healthy volunteers served as controls. The time domain long-term HRV parameters were recorded by a digicorder recorder calculated by ambulatory electrocardiograms. Variabilities in time domain were lower in the MS patients: SDNN (standard deviation of all R-R intervals, p = 0,019), SDANN (standard deviation of the averages of R-R intervals in all 5-minute segments of the entire recordings, p = 0,040), RMSSD (the square root of the mean of the sum of the squares of differences between adjacent R-R intervals, p = 0,026), HRVM (mean of the SDNN in all the 5-minute intervals, p = 0,029), HRVSD (standard deviation of the SDNN in all the 5-minute, p = 0,043). These results suggest that MS causes CAD manifesting as long-term HRV abnormalities. This illness seems to cause a dysfunction in parasympathetic cardiovascular tone. Depressed HRV parameters are independent from the clinicalfindings, but the illness progression partially seems to provoke a decrease in such parameters.

  1. Analyzing CRISM Data from mound B in Juventae Chasma, Mars, with the Multiple-Endmember Linear Spectral Unmixing Model MELSUM

    NASA Astrophysics Data System (ADS)

    Wendt, L.; Gross, C.; McGuire, P. C.; Combe, J.-P.; Neukum, G.

    2009-04-01

    Juventae Chasma, just north of Valles Marineris on Mars, contains several light-toned deposits (LTD), one of which is labelled mound B. Based on IR data from the imaging spectrometer OMEGA on Mars Express,[1] suggested kieserite for the lower part and gypsum for the upper part of the mound. In this study, we analyzed NIR data from the Compact Reconnaissance Imaging Spectrometer CRISM on MRO with the Multiple-Endmember Linear Spectral Unmixing Model MELSUM developed by Combe et al.[2]. We used CRISM data product FRT00009C0A from 1 to 2.6 µm. A novel, time-dependent volcano-scan technique [3] was applied to remove absorption bands related to CO2 much more effectively than the volcano-scan technique [4] that has been applied to CRISM and OMEGA data so far. In the classic SMA, a solution for the measured spectrum is calculated by a linear combination of all input spectra (which may come from a spectral library or from the image itself) at once. This can lead to negative coefficients, which have no physical meaning. MELSUM avoids this by calculating a solution for each possible combination of a subset of the reference spectra, with the maximum number of library spectra in the subset defined by the user. The solution with the lowest residual to the input spectrum is returned. We used MELSUM in a first step as similarity measure within the image by using averaged spectra from the image itself as input to MELSUM. This showed that three spectral units are enough to describe the variability in the data to first order: A lower, light-toned unit, an upper light-toned unit and a dark-toned unit. We then chose 34 laboratory spectra of sulfates, mafic minerals and iron oxides plus a spectrum for H2O ice as reference spectra for the unmixing of averaged spectra for each of these spectral regions. The best fit for the dark material was a combination of olivine, pyroxene and ice (present as cloud in the atmosphere and not on the surface). In agreement with [5], The lower unit was

  2. Through-container, extremely low concentration detection of multiple chemical markers of counterfeit alcohol using a handheld SORS device.

    PubMed

    Ellis, David I; Eccles, Rebecca; Xu, Yun; Griffen, Julia; Muhamadali, Howbeer; Matousek, Pavel; Goodall, Ian; Goodacre, Royston

    2017-09-21

    Major food adulteration incidents occur with alarming frequency and are episodic, with the latest incident, involving the adulteration of meat from 21 producers in Brazil supplied to 60 other countries, reinforcing this view. Food fraud and counterfeiting involves all types of foods, feed, beverages, and packaging, with the potential for serious health, as well as significant economic and social impacts. In the spirit drinks sector, counterfeiters often 'recycle' used genuine packaging, or employ good quality simulants. To prove that suspect products are non-authentic ideally requires accurate, sensitive, analysis of the complex chemical composition while still in its packaging. This has yet to be achieved. Here, we have developed handheld spatially offset Raman spectroscopy (SORS) for the first time in a food or beverage product, and demonstrate the potential for rapid in situ through-container analysis; achieving unequivocal detection of multiple chemical markers known for their use in the adulteration and counterfeiting of Scotch whisky, and other spirit drinks. We demonstrate that it is possible to detect a total of 10 denaturants/additives in extremely low concentrations without any contact with the sample; discriminate between and within multiple well-known Scotch whisky brands, and detect methanol concentrations well below the maximum human tolerable level.

  3. Adaptive marker-free registration using a multiple point strategy for real-time and robust endoscope electromagnetic navigation.

    PubMed

    Luo, Xiongbiao; Wan, Ying; He, Xiangjian; Mori, Kensaku

    2015-02-01

    Registration of pre-clinical images to physical space is indispensable for computer-assisted endoscopic interventions in operating rooms. Electromagnetically navigated endoscopic interventions are increasingly performed at current diagnoses and treatments. Such interventions use an electromagnetic tracker with a miniature sensor that is usually attached at an endoscope distal tip to real time track endoscope movements in a pre-clinical image space. Spatial alignment between the electromagnetic tracker (or sensor) and pre-clinical images must be performed to navigate the endoscope to target regions. This paper proposes an adaptive marker-free registration method that uses a multiple point selection strategy. This method seeks to address an assumption that the endoscope is operated along the centerline of an intraluminal organ which is easily violated during interventions. We introduce an adaptive strategy that generates multiple points in terms of sensor measurements and endoscope tip center calibration. From these generated points, we adaptively choose the optimal point, which is the closest to its assigned the centerline of the hollow organ, to perform registration. The experimental results demonstrate that our proposed adaptive strategy significantly reduced the target registration error from 5.32 to 2.59 mm in static phantoms validation, as well as from at least 7.58 mm to 4.71 mm in dynamic phantom validation compared to current available methods.

  4. Diagnostic Peptide Discovery: Prioritization of Pathogen Diagnostic Markers Using Multiple Features

    PubMed Central

    Carmona, Santiago J.; Sartor, Paula A.; Leguizamón, María S.; Campetella, Oscar E.; Agüero, Fernán

    2012-01-01

    The availability of complete pathogen genomes has renewed interest in the development of diagnostics for infectious diseases. Synthetic peptide microarrays provide a rapid, high-throughput platform for immunological testing of potential B-cell epitopes. However, their current capacity prevent the experimental screening of complete “peptidomes”. Therefore, computational approaches for prediction and/or prioritization of diagnostically relevant peptides are required. In this work we describe a computational method to assess a defined set of molecular properties for each potential diagnostic target in a reference genome. Properties such as sub-cellular localization or expression level were evaluated for the whole protein. At a higher resolution (short peptides), we assessed a set of local properties, such as repetitive motifs, disorder (structured vs natively unstructured regions), trans-membrane spans, genetic polymorphisms (conserved vs. divergent regions), predicted B-cell epitopes, and sequence similarity against human proteins and other potential cross-reacting species (e.g. other pathogens endemic in overlapping geographical locations). A scoring function based on these different features was developed, and used to rank all peptides from a large eukaryotic pathogen proteome. We applied this method to the identification of candidate diagnostic peptides in the protozoan Trypanosoma cruzi, the causative agent of Chagas disease. We measured the performance of the method by analyzing the enrichment of validated antigens in the high-scoring top of the ranking. Based on this measure, our integrative method outperformed alternative prioritizations based on individual properties (such as B-cell epitope predictors alone). Using this method we ranked 10 million 12-mer overlapping peptides derived from the complete T. cruzi proteome. Experimental screening of 190 high-scoring peptides allowed the identification of 37 novel epitopes with diagnostic potential, while none

  5. DIFFERENTIAL ANALYZER

    DOEpatents

    Sorensen, E.G.; Gordon, C.M.

    1959-02-10

    Improvements in analog eomputing machines of the class capable of evaluating differential equations, commonly termed differential analyzers, are described. In general form, the analyzer embodies a plurality of basic computer mechanisms for performing integration, multiplication, and addition, and means for directing the result of any one operation to another computer mechanism performing a further operation. In the device, numerical quantities are represented by the rotation of shafts, or the electrical equivalent of shafts.

  6. Correlations among different markers determined by immunochemical methods used for the diagnosis and monitoring of intact immunoglobulin multiple myeloma cases.

    PubMed

    Dogaru, Monica; Lazăr, Veronica; Coriu, Daniel

    2012-01-01

    The purpose of this study was to determine the correlations between the concentration of free light chains (kappa, lambda and ratio kappa/lambda) and two other markers, M- protein and pathological total intact immunoglobulin in four groups of patients with intact immunoglobulin multiple myeloma (IIMM) at the diagnosis and during the treatment. In this study 354 samples coming from 46 patients with IIMM were assayed, out of which: 19, IgGkappa; 13, IgGlambda; 7, IgAkappa; 7, IgAlambda. At the diagnosis, immunofixation was positive in all samples and serum protein electrophoresis quantified M- protein for all patients. Free light chains concentrations were abnormal in 92.25% of patients with concentrations above the reference ranges in all patients with IgGkappa and IgAkappa MM. The intact immunoglobulins were elevated in 83.12% of cases. Pearson correlation coefficient showed correlations among the free light chains serum levels (kappa, lambda and ratio kappa/lambda), M- protein and intact immunoglobulins in two groups with IIMM (IgGlambda, IgAlambda). Spearman correlation coefficient values analysis showed that there is a good correlation between M-protein and FLCs (kappa, lambda and ratio kappa/lambda) in three patient groups (IgGkappa, IgGlambda and IgAlambda), excepting IgAkappa myeloma group where the correlation was insignificant. Regarding the intact immunoglobulin, Spearman coefficient showed significant correlations with FLCs concentrations in two groups (IgGlambda and IgAlambda) and an insignificant correlation in the group with IgGkappa MM. For the group of patients with IgAkappa myeloma, the Spearman coefficient showed that IgA concentrations did not correlate with the concentrations of FLCs. The individual correlation (for each patient) among FLCs, M- protein and intact immunoglobulins in 8 patients with IgGkappa IIMM proved to be more significant as compared with the degree of correlation established for the entire group of patients among these markers

  7. Analyzing Multiple Informant Data on Child and Adolescent Behavior Problems: Predictive Validity and Comparison of Aggregation Procedures

    ERIC Educational Resources Information Center

    van Dulmen, Manfred H. M.; Egeland, Byron

    2011-01-01

    We compared the predictive validity of five aggregation methods for multiple informant data on child and adolescent behavior problems. In addition, we compared the predictive validity of these aggregation methods with single informant scores. Data were derived from the Minnesota Longitudinal Study of Parents and Children (N = 175). Maternal and…

  8. Analyzing Multiple Informant Data on Child and Adolescent Behavior Problems: Predictive Validity and Comparison of Aggregation Procedures

    ERIC Educational Resources Information Center

    van Dulmen, Manfred H. M.; Egeland, Byron

    2011-01-01

    We compared the predictive validity of five aggregation methods for multiple informant data on child and adolescent behavior problems. In addition, we compared the predictive validity of these aggregation methods with single informant scores. Data were derived from the Minnesota Longitudinal Study of Parents and Children (N = 175). Maternal and…

  9. Tubulin polymerization promoting protein (TPPP/p25) as a marker for oligodendroglial changes in multiple sclerosis.

    PubMed

    Höftberger, Romana; Fink, Stephanie; Aboul-Enein, Fahmy; Botond, Gergö; Olah, Judit; Berki, Timea; Ovadi, Judit; Lassmann, Hans; Budka, Herbert; Kovacs, Gabor G

    2010-11-15

    Multiple sclerosis (MS) is an idiopathic chronic inflammatory demyelinating disease of the central nervous system with variable extent of remyelination. Remyelination originates from oligodendrocyte (OG) precursor cells, which migrate and differentiate into mature OG. Tubulin polymerization promoting protein (TPPP/p25) is located in mature OG and aggregates in oligodendroglial cytoplasmic inclusions in multiple system atrophy. We developed a novel monoclonal anti-TPPP/p25 antibody to quantify OG in different subtypes and disease stages of MS, and possible degenerative changes in OG. We evaluated autopsy material from 25 MS cases, including acute, primary progressive, secondary progressive, relapsing remitting MS, and five controls. Demyelinated lesions revealed loss of TPPP/p25-positive OG within the plaques. In remyelination, TPPP/p25 was first expressed in OG cytoplasms and later became positive in myelin sheaths. We observed increased numbers of TPPP/p25 immunoreactive OG in the normal appearing white matter (NAWM) in MS patients. In MS cases, the cytoplasmic area of TPPP/p25 immunoreactivity in the OG was higher in the periplaque area when compared with NAWM and the plaque, and TPPP/p25 immunoreactive OG cytoplasmic area inversely correlated with the disease duration. There was a lack of phospho-TDP-43, phospho-tau, α-synuclein, and ubiquitin immunoreactivity in OG with enlarged cytoplasm. Our data suggest impaired differentiation, migration, and activation capacity of OG in later disease stages of MS. Upregulation of TPPP/p25 in the periplaque white matter OG without evidence for inclusion body formation might reflect an activation state. Distinct and increased expression of TPPP/p25 in MS renders it a potential prognostic and diagnostic marker of MS.

  10. Identification of Association Between SSR Markers and Fiber Traits in an Exotic Germplasm Population Derived from Multiple Crosses Among Gossypium Species

    USDA-ARS?s Scientific Manuscript database

    Cotton germplasm needs to be enhanced in order to meet the needs of modern textile industry in USA and international competition. An exotic germplam population derived from multiple crosses among tetraploid species was used to identify association between SSR markers and fiber traits. Two hundred an...

  11. Determination of five sesquiterpenoids in Xingnaojing injection by quantitative analysis of multiple components with a single marker.

    PubMed

    Pan, Weidong; Yang, Lixin; Feng, Weihong; Lin, Limei; Li, Chun; Liu, Weiwei; Gan, Guofeng; Fan, Junhong; Zou, Jigao; Wang, Zhimin; Pan, Haifeng

    2015-10-01

    A quantitative analysis of multiple components with a single-marker method was established for the simultaneous determination of five sesqutiterpenoids in Xingnaojing injection. This method was established with Xingnaojing injection determined by high-performance liquid chromatography coupled with diode array detection. The durability and system suitability of the established method were evaluated, and the reliable relative correction factors were obtained with curdione selected as an internal reference. The contents of the five components in all Xingnaojing injections were determined by external standard method and the contents of curcumenone, curcumenol, curzerenone, and germacrone were also calculated with the obtained relative correction factors. Then, relative error was investigated to estimate the difference of the two methods. As a result, the established new method possesses good adaptability, and there is no significant difference between the two methods, except for the content of curzerenone in eight samples. To put the established method into practice, the limits of quantitation of the established method of the five components were proposed and defined. Thus, the developed methodology can also be utilized to the quality evaluation of Xingnaojing injection, in spite of the difference found in the content of curzerenone between the external standard method and the newly established method.

  12. Increased sialylation of oligosaccharides on IgG paraproteins--a potential new tumour marker in multiple myeloma.

    PubMed Central

    Fleming, S C; Smith, S; Knowles, D; Skillen, A; Self, C H

    1998-01-01

    AIMS: To investigate whether changes in carbohydrate structure of IgG are related to malignancy and stage of disease in myeloma and monoclonal gammopathy of uncertain significance (MGUS). METHODS: 61 patients were studied at diagnosis: 14 with MGUS, nine with stage I multiple myeloma, 11 with stage II, 21 with stage III, and five with solitary plasmacytoma. IgG was extracted from serum by protein G affinity chromatography. Oligosaccharides were cleaved from the protein backbone enzymatically by N-glycosidase F. Oligosaccharide analysis was performed by high pressure anion exchange chromatography with pulsed electrochemical detection (HPAE-PED). RESULTS: Up to 15 oligosaccharide peaks were identified in three major fractions: neutral, monosialylated, and disialylated. Patients with myeloma showed an increase in the proportion of sialylated oligosaccharides in comparison with patients with MGUS. The ratio of neutral to sialylated oligosaccharides (N:S) was reduced at all stages of myeloma compared with MGUS: MGUS, 11.35; myeloma stage I, 7.6 (p = 0.047); stage II, 5.20 (p = 0.035); stage III, 3.60 (p = 0.0002); plasmacytoma, 7.5 (p = 0.046). The N:S ratio was independent of paraprotein concentration (r = 0.05). CONCLUSIONS: The ratio of neutral to sialylated oligosaccharides may act as a new marker of malignancy in IgG paraproteinaemia and warrants further investigation. Images PMID:10193323

  13. Genotype-based association mapping of complex diseases: gene-environment interactions with multiple genetic markers and measurement error in environmental exposures.

    PubMed

    Lobach, Iryna; Fan, Ruzong; Carroll, Raymond J

    2010-12-01

    With the advent of dense single nucleotide polymorphism genotyping, population-based association studies have become the major tools for identifying human disease genes and for fine gene mapping of complex traits. We develop a genotype-based approach for association analysis of case-control studies of gene-environment interactions in the case when environmental factors are measured with error and genotype data are available on multiple genetic markers. To directly use the observed genotype data, we propose two genotype-based models: genotype effect and additive effect models. Our approach offers several advantages. First, the proposed risk functions can directly incorporate the observed genotype data while modeling the linkage disequilibrium information in the regression coefficients, thus eliminating the need to infer haplotype phase. Compared with the haplotype-based approach, an estimating procedure based on the proposed methods can be much simpler and significantly faster. In addition, there is no potential risk due to haplotype phase estimation. Further, by fitting the proposed models, it is possible to analyze the risk alleles/variants of complex diseases, including their dominant or additive effects. To model measurement error, we adopt the pseudo-likelihood method by Lobach et al. [2008]. Performance of the proposed method is examined using simulation experiments. An application of our method is illustrated using a population-based case-control study of association between calcium intake with the risk of colorectal adenoma development.

  14. Genotype-Based Association Mapping of Complex Diseases: Gene-Environment Interactions with Multiple Genetic Markers and Measurement Error in Environmental Exposures

    PubMed Central

    Lobach, Irvna; Fan, Ruzone; Carroll, Raymond T.

    2011-01-01

    With the advent of dense single nucleotide polymorphism genotyping, population-based association studies have become the major tools for identifying human disease genes and for fine gene mapping of complex traits. We develop a genotype-based approach for association analysis of case-control studies of gene-environment interactions in the case when environmental factors are measured with error and genotype data are available on multiple genetic markers. To directly use the observed genotype data, we propose two genotype-based models: genotype effect and additive effect models. Our approach offers several advantages. First, the proposed risk functions can directly incorporate the observed genotype data while modeling the linkage disequihbrium information in the regression coefficients, thus eliminating the need to infer haplotype phase. Compared with the haplotype-based approach, an estimating procedure based on the proposed methods can be much simpler and significantly faster. In addition, there is no potential risk due to haplotype phase estimation. Further, by fitting the proposed models, it is possible to analyze the risk alleles/variants of complex diseases, including their dominant or additive effects. To model measurement error, we adopt the pseudo-likelihood method by Lobach et al. [2008]. Performance of the proposed method is examined using simulation experiments. An application of our method is illustrated using a population-based case-control study of association between calcium intake with the risk of colorectal adenoma development. PMID:21031455

  15. Analyzing the trade-off between multiple memory controllers and memory channels on multi-core processor performance

    SciTech Connect

    Sancho Pitarch, Jose Carlos; Kerbyson, Darren; Lang, Mike

    2010-01-01

    Increasing the core-count on current and future processors is posing critical challenges to the memory subsystem to efficiently handle concurrent memory requests. The current trend to cope with this challenge is to increase the number of memory channels available to the processor's memory controller. In this paper we investigate the effectiveness of this approach on the performance of parallel scientific applications. Specifically, we explore the trade-off between employing multiple memory channels per memory controller and the use of multiple memory controllers. Experiments conducted on two current state-of-the-art multicore processors, a 6-core AMD Istanbul and a 4-core Intel Nehalem-EP, for a wide range of production applications shows that there is a diminishing return when increasing the number of memory channels per memory controller. In addition, we show that this performance degradation can be efficiently addressed by increasing the ratio of memory controllers to channels while keeping the number of memory channels constant. Significant performance improvements can be achieved in this scheme, up to 28%, in the case of using two memory controllers with each with one channel compared with one controller with two memory channels.

  16. Neutrophil Gelatinase--Associated Lipocalin and Cystatin C Are Sensitive Markers of Renal Injury in Patients With Multiple Myeloma.

    PubMed

    Papassotiriou, Gerasimos-Petros; Kastritis, Efstathios; Gkotzamanidou, Maria; Christoulas, Dimitrios; Eleutherakis-Papaiakovou, Evangelos; Migkou, Magdalini; Gavriatopoulou, Maria; Roussou, Maria; Margeli, Alexandra; Papassotiriou, Ioannis; Dimopoulos, Meletios A; Terpos, Evangelos

    2016-01-01

    Renal impairment is a common complication of patients with multiple myeloma (MM). We aimed to evaluate the clinical significance of 2 newly discovered biomarkers of renal injury, cystatin C (CysC), a protein reflecting glomerular filtration rate, and neutrophil gelatinase-associated lipocalin (NGAL), a protein reflecting tubular injuries. We studied 64 patients with newly diagnosed myeloma: 16 with asymptomatic (smoldering) MM and 48 with symptomatic myeloma; 8 patients with monoclonal gammopathy of undetermined significance (MGUS); and 20 healthy control subjects. Along with common blood and urine chemistry determinations, measurements of CysC, NGAL, β2-microglobulin, high-sensitivity C-reactive protein, and interleukin 6 were performed. We found that only patients with symptomatic MM had increased levels of CysC compared to controls (P < .01); that serum NGAL levels were elevated in all patients compared to controls P < .001; that NGAL strongly correlated with both estimation of glomerular filtration rate (eGFR) (CysC) and eGFR (Modification of Diet in Renal Disease [MDRD] formula) (r = 0.616, P < .0001; and r = -0.371, P < .01, respectively); that CysC showed strong correlation with eGFR (r = -0.782, P < .001) and with the International Scoring System (ISS) (more pronounced in patients with ISS-3); and that receiver operating characteristic curve analysis showed that NGAL values of > 50.5 μg/L have a 80.8% sensitivity and 86.4% specificity for eGFR < 60 mL/min (area under the curve = 0.764). These findings suggest that both NGAL and CysC are very sensitive markers that reflect renal impairment in newly diagnosed patients with MM. The high levels of NGAL in asymptomatic patients and in MGUS patients support the hypothesis of the presence of renal damage in these patients early in the course of their disease and may reveal NGAL to be an early marker that predicts the presence of renal impairment in MM. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Assessing genetic structure with multiple classes of molecular markers: a case study involving the introduced fire ant Solenopsis invicta.

    PubMed

    Ross, K G; Shoemaker, D D; Krieger, M J; DeHeer, C J; Keller, L

    1999-04-01

    We used 30 genetic markers of 6 different classes to describe hierarchical genetic structure in introduced populations of the fire ant Solenopsis invicta. These included four classes of presumably neutral nuclear loci (allozymes, codominant random amplified polymorphic DNAs (RAPDs), microsatellites, and dominant RAPDs), a class comprising two linked protein-coding nuclear loci under selection, and a marker of the mitochondrial DNA (mtDNA). Patterns of structure revealed by F statistics and exact tests of differentiation were highly concordant among the four classes of neutral nuclear markers, although the microsatellites were the most effective markers for detecting structure. The results from the mtDNA complemented those from the neutral nuclear markers by revealing that strong limitations to female-mediated gene flow were the cause of the local structure registered by the nuclear markers. The pattern of structure inferred from the selected nuclear loci was markedly different from the patterns derived from the other sets of markers but was predictable on the basis of the presumed mode of selection acting on these loci. In general, the results for all six classes of markers can be explained by known features of the social and reproductive biology of fire ants. Thus, the results from these diverse sets of markers, combined with detailed natural history data, provide an unusually complete picture of how the fundamental evolutionary forces of gene flow, drift, and selection govern the distribution of genetic variation within and between fire ant populations.

  18. Multiple target drug cocktail design for attacking the core network markers of four cancers using ligand-based and structure-based virtual screening methods

    PubMed Central

    2015-01-01

    Background Computer-aided drug design has a long history of being applied to discover new molecules to treat various cancers, but it has always been focused on single targets. The development of systems biology has let scientists reveal more hidden mechanisms of cancers, but attempts to apply systems biology to cancer therapies remain at preliminary stages. Our lab has successfully developed various systems biology models for several cancers. Based on these achievements, we present the first attempt to combine multiple-target therapy with systems biology. Methods In our previous study, we identified 28 significant proteins--i.e., common core network markers--of four types of cancers as house-keeping proteins of these cancers. In this study, we ranked these proteins by summing their carcinogenesis relevance values (CRVs) across the four cancers, and then performed docking and pharmacophore modeling to do virtual screening on the NCI database for anti-cancer drugs. We also performed pathway analysis on these proteins using Panther and MetaCore to reveal more mechanisms of these cancer house-keeping proteins. Results We designed several approaches to discover targets for multiple-target cocktail therapies. In the first one, we identified the top 20 drugs for each of the 28 cancer house-keeping proteins, and analyzed the docking pose to further understand the interaction mechanisms of these drugs. After screening for duplicates, we found that 13 of these drugs could target 11 proteins simultaneously. In the second approach, we chose the top 5 proteins with the highest summed CRVs and used them as the drug targets. We built a pharmacophore and applied it to do virtual screening against the Life-Chemical library for anti-cancer drugs. Based on these results, wet-lab bio-scientists could freely investigate combinations of these drugs for multiple-target therapy for cancers, in contrast to the traditional single target therapy. Conclusions Combination of systems biology

  19. Multiple target drug cocktail design for attacking the core network markers of four cancers using ligand-based and structure-based virtual screening methods.

    PubMed

    Wong, Yung-Hao; Lin, Chih-Lung; Chen, Ting-Shou; Chen, Chien-An; Jiang, Pei-Shin; Lai, Yi-Hua; Chu, Lichieh; Li, Cheng-Wei; Chen, Jeremy J W; Chen, Bor-Sen

    2015-01-01

    Computer-aided drug design has a long history of being applied to discover new molecules to treat various cancers, but it has always been focused on single targets. The development of systems biology has let scientists reveal more hidden mechanisms of cancers, but attempts to apply systems biology to cancer therapies remain at preliminary stages. Our lab has successfully developed various systems biology models for several cancers. Based on these achievements, we present the first attempt to combine multiple-target therapy with systems biology. In our previous study, we identified 28 significant proteins--i.e., common core network markers--of four types of cancers as house-keeping proteins of these cancers. In this study, we ranked these proteins by summing their carcinogenesis relevance values (CRVs) across the four cancers, and then performed docking and pharmacophore modeling to do virtual screening on the NCI database for anti-cancer drugs. We also performed pathway analysis on these proteins using Panther and MetaCore to reveal more mechanisms of these cancer house-keeping proteins. We designed several approaches to discover targets for multiple-target cocktail therapies. In the first one, we identified the top 20 drugs for each of the 28 cancer house-keeping proteins, and analyzed the docking pose to further understand the interaction mechanisms of these drugs. After screening for duplicates, we found that 13 of these drugs could target 11 proteins simultaneously. In the second approach, we chose the top 5 proteins with the highest summed CRVs and used them as the drug targets. We built a pharmacophore and applied it to do virtual screening against the Life-Chemical library for anti-cancer drugs. Based on these results, wet-lab bio-scientists could freely investigate combinations of these drugs for multiple-target therapy for cancers, in contrast to the traditional single target therapy. Combination of systems biology with computer-aided drug design could

  20. FBAT-SNP-PC: an approach for multiple markers and single trait in family-based association tests.

    PubMed

    Rakovski, Cyril S; Weiss, Scott T; Laird, Nan M; Lange, Christoph

    2008-01-01

    Develop a new test for family-based association studies and continuous traits that incorporates power- enhancing techniques from two existing testing strategies. The new procedure initiates with an extraction of the relevant information from the variability of the genotypes and an assessment of the approximate individual markers effects and their directions. This information is incorporated in the construction of the actual test statistic through a selection of a data-determined number of optimal linear combinations of the offspring genotypes which, in a power enhancing step, are consequently combined into a single degree of freedom test. We conduct a comparison simulation study in which the performance of the new test is contrasted with the test that is currently known to offer the highest overall power, FBAT-LC. The new test has an overall performance very similar to that of FBAT-LC but attains higher power in candidate genes with lower average pairwise correlations and moderate to high allele frequencies with large gains (up to 80%) for some of the analyzed genes possessing the above-mentioned characteristics. The new test is a promising tool for candidate gene studies with substantial power gains for genes that are characterized by SNPs with low mean pairwise correlation. (c) 2008 S. Karger AG, Basel

  1. Impact of glatiramer acetate on paraclinical markers of neuroprotection in multiple sclerosis: A prospective observational clinical trial.

    PubMed

    Ehling, Rainer; Di Pauli, Franziska; Lackner, Peter; Rainer, Carolyn; Kraus, Viktoria; Hegen, Harald; Lutterotti, Andreas; Kuenz, Bettina; De Zordo, Tobias; Schocke, Michael; Glatzl, Susanne; Löscher, Wolfgang N; Deisenhammer, Florian; Reindl, Markus; Berger, Thomas

    2015-10-15

    Data from in vitro and animal studies support a neuroprotective role of glatiramer acetate (GA) in multiple sclerosis (MS). We investigated prospectively whether treatment with GA leads to clinical and paraclinical changes associated with neuroprotection in patients with relapsing-remitting (RR) MS. Primary aim of this clinical study was to determine serum BDNF levels in RR-MS patients who were started on GA as compared to patients who remained therapy-naive throughout 24 months. Secondary outcomes included relapses and EDSS, cognition, quality of life, fatigue and depression, BDNF expression levels on peripheral immune cells (FACS, RT-PCR), serum anti-myelin basic peptide (MBP) antibody status, evoked potential and cerebral MRI studies. While GA treatment did not alter serum levels or expression levels on peripheral immune cells of BDNF over time it resulted in a transient increase of serum IgG antibody response to MBP, mainly due to subtype IgG1 (p<0.05), after 3 months. However, no significant differences were found between GA treated and therapy-naive patients with regard to serum BDNF and intracellular BDNF expression levels, nerve conduction (including median and tibial nerve somatosensory, pattern-shift visual and upper and lower limb motor evoked potentials) or MRI (including volume of hyperintense lesions, volume of hypointense lesions after CE, mean diffusivity and fractional anisotropy) outcome parameters. In conclusion, our findings do not support a major impact of GA treatment on paraclinical markers of neuroprotection in human RR-MS. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Reduction of Respiratory Liver Tumor Motion by Abdominal Compression in Stereotactic Body Frame, Analyzed by Tracking Fiducial Markers Implanted in Liver

    SciTech Connect

    Wunderink, Wouter Mendez Romero, Alejandra; Kruijf, Willy de; Boer, Hans de; Levendag, Peter; Heijmen, Ben

    2008-07-01

    Purpose: To investigate in a three-dimensional framework the effectiveness and reproducibility of reducing the respiratory motion of liver tumors using abdominal compression in a stereotactic body frame. Methods and Materials: A total of 12 patients with liver tumors, who were treated with stereotactic body radiotherapy, were included in this study. These patients had three gold fiducial markers implanted in the healthy liver tissue surrounding the tumor. Fluoroscopic videos were acquired on the planning day and before each treatment fraction to visualize the motion of the fiducial markers during free breathing and varying levels of abdominal compression. Software was developed to track the fiducial markers and measure their excursions. Results: Abdominal compression reduced the patient group median excursion by 62% in the craniocaudal and 38% in the anteroposterior direction with respect to the median free-breathing excursions. In the left-right direction, the median excursion increased 15% (maximal increase 1.6 mm). The median residual excursion was 4.1 mm in the craniocaudal, 2.4 mm in the anteroposterior, and 1.8 mm in the left-right direction. The mean excursions were reduced by compression to <5 mm in all patients and all directions, with two exceptions (craniocaudal excursion reduction of 20.5 mm to 7.4 mm and of 21.1 mm to 5.9 mm). The residual excursions reproduced well during the treatment course, and the craniocaudal excursions measured on the treatment days were never significantly ({alpha} = 0.05) greater than on the planning days. Fine tuning the compression did not considerably change the excursion on the treatment days. Conclusions: Abdominal compression effectively reduced liver tumor motion, yielding small and reproducible excursions in three dimensions. The compression level established at planning could have been safely used on the treatment days.

  3. Statistical classification of multivariate flow cytometry data analyzed by manual gating: stem, progenitor, and epithelial marker expression in nonsmall cell lung cancer and normal lung.

    PubMed

    Normolle, Daniel P; Donnenberg, Vera S; Donnenberg, Albert D

    2013-01-01

    The use of supervised classification to extract markers from primary flow cytometry data is an emerging field that has made significant progress, spurred by the growing complexity of multidimensional flow cytometry. Whether the markers are extracted without supervision or by conventional gate and region methods, the number of candidate variables identified is typically larger than the number of specimens (p > n) and many variables are highly intercorrelated. Thus, comparison across groups or treatments to determine which markers are significant is challenging. Here, we utilized a data set in which 86 variables were created by conventional manual analysis of individual listmode data files, and compared the application of five multivariate classification methods to discern subtle differences between the stem/progenitor content of 35 nonsmall cell lung cancer and adjacent normal lung specimens. The methods compared include elastic-net, lasso, random forest, diagonal linear discriminant analysis, and best single variable (best-1). We described a broadly applicable methodology consisting of: 1) variable transformation and standardization; 2) visualization and assessment of correlation between variables; 3) selection of significant variables and modeling; and 4) characterization of the quality and stability of the model. The analysis yielded both validating results (tumors are aneuploid and have higher light scatter properties than normal lung), as well as leads that require followup: Cytokeratin+ CD133+ progenitors are present in normal lung but reduced in lung cancer; diploid (or pseudo-diploid) CD117+CD44+ cells are more prevalent in tumor. We anticipate that the methods described here will be broadly applicable to a variety of multidimensional cytometry problems.

  4. Multiple Origins of Mutations in the mdr1 Gene—A Putative Marker of Chloroquine Resistance in P. vivax

    PubMed Central

    Schousboe, Mette L.; Ranjitkar, Samir; Rajakaruna, Rupika S.; Amerasinghe, Priyanie H.; Morales, Francisco; Pearce, Richard; Ord, Rosalyn; Leslie, Toby; Rowland, Mark; Gadalla, Nahla B.; Konradsen, Flemming; Bygbjerg, Ib C.; Roper, Cally; Alifrangis, Michael

    2015-01-01

    Background Chloroquine combined with primaquine has been the recommended antimalarial treatment of Plasmodium vivax malaria infections for six decades but the efficacy of this treatment regimen is threatened by chloroquine resistance (CQR). Single nucleotide polymorphisms (SNPs) in the multidrug resistance gene, Pvmdr1 are putative determinants of CQR but the extent of their emergence at population level remains to be explored. Objective In this study we describe the prevalence of SNPs in the Pvmdr1 among samples collected in seven P. vivax endemic countries and we looked for molecular evidence of drug selection by characterising polymorphism at microsatellite (MS) loci flanking the Pvmdr1 gene. Methods We examined the prevalence of SNPs in the Pvmdr1 gene among 267 samples collected from Pakistan, Afghanistan, Sri Lanka, Nepal, Sudan, São Tomé and Ecuador. We measured and diversity in four microsatellite (MS) markers flanking the Pvmdr1 gene to look evidence of selection on mutant alleles. Results SNP polymorphism in the Pvmdr1 gene was largely confined to codons T958M, Y976F and F1076L. Only 2.4% of samples were wildtype at all three codons (TYF, n = 5), 13.3% (n = 28) of the samples were single mutant MYF, 63.0% of samples (n = 133) were double mutant MYL, and 21.3% (n = 45) were triple mutant MFL. Clear geographic differences in the prevalence of these Pvmdr mutation combinations were observed. Significant linkage disequilibrium (LD) between Pvmdr1 and MS alleles was found in populations sampled in Ecuador, Nepal and Sri Lanka, while significant LD between Pvmdr1 and the combined 4 MS locus haplotype was only seen in Ecuador and Sri Lanka. When combining the 5 loci, high level diversity, measured as expected heterozygosity (He), was seen in the complete sample set (He = 0.99), while He estimates for individual loci ranged from 0.00–0.93. Although Pvmdr1 haplotypes were not consistently associated with specific flanking MS alleles, there was significant

  5. Acquisition of the Korean Imperfective Aspect Markers "-ko iss-" and "-a iss-" by Japanese Learners: A Multiple-Factor Account

    ERIC Educational Resources Information Center

    Ryu, Ju-Yeon; Horie, Kaoru; Shirai, Yasuhiro

    2015-01-01

    Although cross-linguistic research on second language tense-aspect acquisition has uncovered universal tendencies concerning the association between verbal semantics and tense-aspect markers, it is still unclear what mechanisms underlie this link. This study investigates the acquisition of two imperfective aspect markers ("-ko iss-" and…

  6. Acquisition of the Korean Imperfective Aspect Markers "-ko iss-" and "-a iss-" by Japanese Learners: A Multiple-Factor Account

    ERIC Educational Resources Information Center

    Ryu, Ju-Yeon; Horie, Kaoru; Shirai, Yasuhiro

    2015-01-01

    Although cross-linguistic research on second language tense-aspect acquisition has uncovered universal tendencies concerning the association between verbal semantics and tense-aspect markers, it is still unclear what mechanisms underlie this link. This study investigates the acquisition of two imperfective aspect markers ("-ko iss-" and…

  7. A high density consensus genetic map of tetraploid cotton that integrates multiple component maps through molecular marker redundancy check

    USDA-ARS?s Scientific Manuscript database

    An ultra-dense consensus (UDC) genetic map of tetraploid cotton was constructed using six high-density component maps and after the integration of a sequence-based marker redundancy check. Public cotton SSR libraries (17,343 markers) were curated for sequence redundancy using 90% as a similarity cut...

  8. A High Density Consensus Genetic Map of Tetraploid Cotton That Integrates Multiple Component Maps through Molecular Marker Redundancy Check

    PubMed Central

    Blenda, Anna; Fang, David D.; Rami, Jean-François; Garsmeur, Olivier; Luo, Feng; Lacape, Jean-Marc

    2012-01-01

    A consensus genetic map of tetraploid cotton was constructed using six high-density maps and after the integration of a sequence-based marker redundancy check. Public cotton SSR libraries (17,343 markers) were curated for sequence redundancy using 90% as a similarity cutoff. As a result, 20% of the markers (3,410) could be considered as redundant with some other markers. The marker redundancy information had been a crucial part of the map integration process, in which the six most informative interspecific Gossypium hirsutum×G. barbadense genetic maps were used for assembling a high density consensus (HDC) map for tetraploid cotton. With redundant markers being removed, the HDC map could be constructed thanks to the sufficient number of collinear non-redundant markers in common between the component maps. The HDC map consists of 8,254 loci, originating from 6,669 markers, and spans 4,070 cM, with an average of 2 loci per cM. The HDC map presents a high rate of locus duplications, as 1,292 markers among the 6,669 were mapped in more than one locus. Two thirds of the duplications are bridging homoeologous AT and DT chromosomes constitutive of allopolyploid cotton genome, with an average of 64 duplications per AT/DT chromosome pair. Sequences of 4,744 mapped markers were used for a mutual blast alignment (BBMH) with the 13 major scaffolds of the recently released Gossypium raimondii genome indicating high level of homology between the diploid D genome and the tetraploid cotton genetic map, with only a few minor possible structural rearrangements. Overall, the HDC map will serve as a valuable resource for trait QTL comparative mapping, map-based cloning of important genes, and better understanding of the genome structure and evolution of tetraploid cotton. PMID:23029214

  9. Development of an inexact-variance hydrological modeling system for analyzing interactive effects of multiple uncertain parameters

    NASA Astrophysics Data System (ADS)

    Wang, C. X.; Li, Y. P.; Zhang, J. L.; Huang, G. H.

    2015-09-01

    Uncertainty assessment of hydrological model parameters has become one of the main topics due to their significant effects on prediction in arid and semi-arid river basins. Incorporation of uncertainty assessment within hydrological models can facilitate the calibration process and improve the degree of credibility to the subsequent prediction. In this study, an inexact-variance hydrological modeling system (IVHMS) is developed for assessing parameter uncertainty on modeling outputs in the Kaidu River Basin, China. Through incorporating the techniques of type-2 fuzzy analysis (T2FA) and analysis of variance (ANOVA) within the semi-distributed land use based runoff processes (SLURP) model, IVHMS can quantitatively evaluate the individual and interactive effects of multiple uncertain parameters expressed as type-2 fuzzy sets in the hydrological modeling system. The modeling outputs indicate a good performance of SLURP model in describing the daily streamflow at the Dashankou hydrological station. Uncertainty analysis is conducted through sampling from fuzzy membership functions under different α-cut levels. The results show that, under a lower degree of plausibility (i.e. a lower α-cut level), intervals for peak and average flows are both wider; while intervals of peak and average flows become narrower under a higher degree of plausibility. Results based on ANOVA reveal that (i) precipitation factor (PF), one of main factors dominating the runoff processes, should be paid more attention in order to enhance the model performance; (ii) retention constant for fast store (RS) controls the amount and timing of the outflow from saturated zone and has a highly nonlinear effect on the average flow; (iii) the interaction between retention constant for fast store (RF) and maximum capacity for fast store (MF) has statistically significant (p < 0.05) effect on modeling outputs through affecting the maximum water holding capacity and the soil infiltration rate. The findings can

  10. Brain-Specific Cytoskeletal Damage Markers in Cerebrospinal Fluid: Is There a Common Pattern between Amyotrophic Lateral Sclerosis and Primary Progressive Multiple Sclerosis?

    PubMed Central

    Abdelhak, Ahmed; Junker, Andreas; Brettschneider, Johannes; Kassubek, Jan; Ludolph, Albert C.; Otto, Markus; Tumani, Hayrettin

    2015-01-01

    Many neurodegenerative disorders share a common pathophysiological pathway involving axonal degeneration despite different etiological triggers. Analysis of cytoskeletal markers such as neurofilaments, protein tau and tubulin in cerebrospinal fluid (CSF) may be a useful approach to detect the process of axonal damage and its severity during disease course. In this article, we review the published literature regarding brain-specific CSF markers for cytoskeletal damage in primary progressive multiple sclerosis and amyotrophic lateral sclerosis in order to evaluate their utility as a biomarker for disease progression in conjunction with imaging and histological markers which might also be useful in other neurodegenerative diseases associated with affection of the upper motor neurons. A long-term benefit of such an approach could be facilitating early diagnostic and prognostic tools and assessment of treatment efficacy of disease modifying drugs. PMID:26263977

  11. Organic pollutant levels in an agricultural watershed: the importance of analyzing multiple matrices for assessing stream water pollution.

    PubMed

    Gonzalez, Mariana; Miglioranza, Karina S B; Grondona, Sebastían I; Silva Barni, Maria Florencia; Martinez, Daniel E; Peña, Aránzazu

    2013-04-01

    This study is aimed at analyzing the occurrence and transport of organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) in the Quequén Grande river basin, as representative of a catchment under diffuse pollution sources. Pollutant levels in soils, river bottom sediments (RBS), streamwater (Sw), suspended particle materials (SPMs), macrophytes and muscle of silverside were determined by GC-ECD. Soil K(d) values for the current-used insecticides, endosulfans and cypermethrin, were established. Total levels (ng g(-1) dry weight) in soil ranged between 0.07–0.9 for OCPs, 0.03–0.37 for PCBs and 0.01–0.05 for PBDEs. Endosulfan insecticide (α- + b- + sulfate metabolite) represented up to 72.5% of OCPs. The low soil retention for α-endosulfan (K(d): 77) and endosulfan sulfate (K(d): 100) allows their transport to Sw, SPM and RBS. Levels of endosulfan in Sw in some cases exceeded the value postulated by international guidelines for aquatic biota protection (3 ng L(-1)). PCB and PBDE pollution was related to harbour, dumping sites and pile tire burning. Tri and hexa PCB congeners predominated in all matrices and exceeded the quality guideline value of 0.04 ng L(-1) in Sw. Considering levels in silverside muscle, none of the oral reference doses were exceeded, however, PCBs accounted for 18.6% of the total daily allowed ingest for a 70 kg individual. Although the levels of PCBs and OCPs in soil and RBS were low and did not go beyond quality guidelines, these compounds could still represent a risk to aquatic biota and humanbeings, and thus actions towards preventing this situation should be undertaken.

  12. Diagnosis of Bacteriuria by Detection of Volatile Organic Compounds in Urine Using an Automated Headspace Analyzer with Multiple Conducting Polymer Sensors

    PubMed Central

    Aathithan, S.; Plant, J. C.; Chaudry, A. N.; French, G. L.

    2001-01-01

    The Osmetech Microbial Analyzer (OMA) is an automated headspace analyzer fitted with a novel detector system consisting of an array of polymer sensors, each of which responds to different volatile organic compounds. The system can be used for screening clinical urine specimens for significant bacteriuria by sampling urine headspace and subjecting the output of the multiple-detector response to principal component analysis. The OMA readily distinguished artificially infected urine samples from sterile controls. The OMA was then used to analyze 534 unselected clinical urine specimens, of which 21.5% had significant bacteriuria (containing >105 CFU of bacteria/ml). The sensitivity and specificity of the OMA compared with conventional culture were 83.5 and 87.6%, respectively. The OMA is a promising automated system for the rapid routine screening of urine specimens, and further clinical trials are in progress. PMID:11427574

  13. [Diversity of diazotrophs in the sediments of hypersaline salt and soda lakes analyzed with the use of the nifH gene as a molecular marker].

    PubMed

    Turova, T P; Slobodova, N V; Bumazhkin, B K; Sukhacheva, M V; Sorokin, D Iu

    2014-01-01

    Phylogenetic analysis of the nifH genes, encoding the Fe protein of the nitrogenas enzymatic complex, was carried out for pure cultures of anoxygenic phototrophic bacteria of diverse origin, as well as for heterotrophic alkaliphilic sulfate reducers isolated from saline and soda lakes. Topology of the nitrogenase tree correlated with that of the 16S rRNAgene tree to a considerable degree; which niade it possible to use the nifH gene as a molecular marker for investigation of diazotrophic bacterialcommunities in silty sediments of saline and sodalakes. Although diazotrophs were revealed in all environmentalsamples, their phylogenetic diversity was relatively low. Sulfate-reducing deltaproteobacteria and photo- and chemotrophicgammaproteobacteria were predominant in samples integrated over sediment thickness. Analysis of samples fromthe upper sediment layers revealed predominance of phototrophic diazotrophs of various phyla, including purple sulfur and nonsulfur proteobacteria, green nonsulfur bacteria, heliobacteria; and cyanobacteria. Some phylotypes could not be identified, probably indicating the presence of bacterial groups which have not yet been studied by conventional microbiological techniques.

  14. Untranslated leader region polymorphism of Tvv1, a retrotransposon family, is a novel marker useful for analyzing genetic diversity and relatedness in the genus Vitis.

    PubMed

    Pelsy, Frédérique

    2007-12-01

    Grapevine retrotransposons belonging to the Tvv1 family share a single, highly conserved open reading frame but differ by their untranslated leader (UTL) region, which is highly variable in size. Amplification of the UTL region of Tvv1 elements from 94 Vitaceae accessions reveals that each of them shows a unique pattern of UTL-derived bands, which is inherited in progenies but conserved between clones vegetatively propagated. The overall organization of genetic diversity of the Vitaceae at the inter and intraspecific level and relatedness among accessions described by UTL-derived bands was compared to those obtained using 15 microsatellite loci. Both fingerprinting methods show a similar grouping of Vitis vinifera accessions but UTL-based fingerprinting more accurately isolates the muscadine grapes from the American and Asian Vitis. Finally, sequence analysis of seven UTL regions determines that their size variation is essentially caused by large deletions/insertions within the internal region, whereas flanking regions are more conserved. UTL-based fingerprinting could be considered as a novel marker system specific of the genus Vitis; moreover, as this multiband genotype is stable between clones it is suitable to be used as a "DNA barcode" for Vitis identification.

  15. Microsatellite markers in plants and insects part II: Databases and in silico tools for microsatellite mining and analyzing population genetic stratification

    USDA-ARS?s Scientific Manuscript database

    Nucleotide sequence information available in searchable sequence databases and the free in silico software with which to extract and analyze microsatellite data continues to grow at a rapid rate across eukaryote taxa. The sheer amount of information available means that a comprehensive or exhaustive...

  16. Molecular marker-based prediction of hybrid performance in maize using unbalanced data from multiple experiments with factorial crosses.

    PubMed

    Schrag, Tobias A; Möhring, Jens; Maurer, Hans Peter; Dhillon, Baldev S; Melchinger, Albrecht E; Piepho, Hans-Peter; Sørensen, Anker P; Frisch, Matthias

    2009-02-01

    In hybrid breeding, the prediction of hybrid performance (HP) is extremely important as it is difficult to evaluate inbred lines in numerous cross combinations. Recent developments such as doubled haploid production and molecular marker technologies have enhanced the prospects of marker-based HP prediction to accelerate the breeding process. Our objectives were to (1) predict HP using a combined analysis of hybrids and parental lines from a breeding program, (2) evaluate the use of molecular markers in addition to phenotypic and pedigree data, (3) evaluate the combination of line per se data with marker-based estimates, (4) study the effect of the number of tested parents, and (5) assess the advantage of haplotype blocks. An unbalanced dataset of 400 hybrids from 9 factorial crosses tested in different experiments and data of 79 inbred parents were subjected to combined analyses with a mixed linear model. Marker data of the inbreds were obtained with 20 AFLP primer-enzyme combinations. Cross-validation was used to assess the performance prediction of hybrids of which no or only one parental line was testcross evaluated. For HP prediction, the highest proportion of explained variance (R (2)), 46% for grain yield (GY) and 70% for grain dry matter content (GDMC), was obtained from line per se best linear unbiased prediction (BLUP) estimates plus marker effects associated with mid-parent heterosis (TEAM-LM). Our study demonstrated that HP was efficiently predicted using molecular markers even for GY when testcross data of both parents are not available. This can help in improving greatly the efficiency of commercial hybrid breeding programs.

  17. Sewage pollution in urban stormwater runoff as evident from the widespread presence of multiple microbial and chemical source tracking markers.

    PubMed

    Sidhu, J P S; Ahmed, W; Gernjak, W; Aryal, R; McCarthy, D; Palmer, A; Kolotelo, P; Toze, S

    2013-10-01

    The concurrence of human sewage contamination in urban stormwater runoff (n=23) from six urban catchments across Australia was assessed by using both microbial source tracking (MST) and chemical source tracking (CST) markers. Out of 23 stormwater samples human adenovirus (HAv), human polyomavirus (HPv) and the sewage-associated markers; Methanobrevibacter smithii nifH and Bacteroides HF183 were detected in 91%, 56%, 43% and 96% of samples, respectively. Similarly, CST markers paracetamol (87%), salicylic acid (78%) acesulfame (96%) and caffeine (91%) were frequently detected. Twenty one samples (91%) were positive for six to eight sewage related MST and CST markers and remaining two samples were positive for five and four markers, respectively. A very good consensus (>91%) observed between the concurrence of the HF183, HAv, acesulfame and caffeine suggests good predictability of the presence of HAv in samples positive for one of the three markers. High prevalence of HAv (91%) also suggests that other enteric viruses may also be present in the stormwater samples which may pose significant health risks. This study underscores the benefits of employing a set of MST and CST markers which could include monitoring for HF183, adenovirus, caffeine and paracetamol to accurately detect human sewage contamination along with credible information on the presence of human enteric viruses, which could be used for more reliable public health risk assessments. Based on the results obtained in this study, it is recommended that some degree of treatment of captured stormwater would be required if it were to be used for non-potable purposes. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

  18. Phylogenetic relationships of the ciliate class Heterotrichea (Protista, Ciliophora, Postciliodesmatophora) inferred from multiple molecular markers and multifaceted analysis strategy.

    PubMed

    Shazib, Shahed Uddin Ahmed; Vd'ačný, Peter; Kim, Ji Hye; Jang, Seok Won; Shin, Mann Kyoon

    2014-09-01

    The ciliate class Heterotrichea is defined by somatic dikinetids bearing postciliodesmata, by an oral apparatus consisting of a paroral membrane and an adoral zone of membranelles, as well as by features of nuclear division involving extramacronuclear microtubules. Although phylogenetic interrelationships among heterotrichs have been analyzed several times, deeper nodes of the heterotrichean tree of life remain poorly resolved. To cast more light on the evolutionary history of heterotricheans, we performed phylogenetic analyses of multiple loci (18S rRNA gene, ITS1-5.8S rRNA-ITS2 region, and 28S rRNA gene) using traditional tree-building phylogenetic methods and statistical tree topology tests as well as phylogenetic networks, split spectrum analysis and quartet likelihood mapping. This multifaceted approach has shown that (1) Peritromus is very likely an adelphotaxon of all other heterotrichs; (2) Spirostomum and Anigsteinia are sister taxa and their common monophyletic origin is strongly supported by a uniquely posteriorly-thickened paroral membrane; (3) the monotypic family Chattonidiidae should be suppressed because its type genus clusters within the family Condylostomatidae; and (4) new families are needed for Gruberia and Fabrea because their affiliation with Spirostomidae and Climacostomidae, respectively, is not supported by molecular phylogenies nor the fine structure of the paroral membrane. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Studies of HVC Plasticity in Adult Canaries Reveal Social Effects and Sex Differences as Well as Limitations of Multiple Markers Available to Assess Adult Neurogenesis

    PubMed Central

    Shevchouk, Olesya T.; Ball, Gregory F.; Cornil, Charlotte A.

    2017-01-01

    In songbirds, neurogenesis in the song control nucleus HVC is sensitive to the hormonal and social environment but the dynamics of this process is difficult to assess with a single exogenous marker of new neurons. We simultaneously used three independent markers to investigate HVC neurogenesis in male and female canaries. Males were castrated, implanted with testosterone and housed either alone (M), with a female (M-F) or with another male (M-M) while females were implanted with 17β-estradiol and housed with a male (F-M). All subjects received injections of the two thymidine analogues, BrdU and of EdU, respectively 21 and 10 days before brain collection. Cells containing BrdU or EdU or expressing doublecortin (DCX), which labels newborn neurons, were quantified. Social context and sex differentially affected total BrdU+, EdU+, BrdU+EdU- and DCX+ populations. M-M males had a higher density of BrdU+ cells in the ventricular zone adjacent to HVC and of EdU+ in HVC than M-F males. M birds had a higher ratio of BrdU+EdU- to EdU+ cells than M-F subjects suggesting higher survival of newer neurons in the former group. Total number of HVC DCX+ cells was lower in M-F than in M-M males. Sex differences were also dependent of the type of marker used. Several technical limitations associated with the use of these multiple markers were also identified. These results indicate that proliferation, recruitment and survival of new neurons can be independently affected by environmental conditions and effects can only be fully discerned through the use of multiple neurogenesis markers. PMID:28141859

  20. Atmosphere Analyzer

    NASA Technical Reports Server (NTRS)

    1982-01-01

    California Measurements, Inc.'s model PC-2 Aerosol Particle Analyzer is produced in both airborne and ground-use versions. Originating from NASA technology, it is a quick and accurate method of detecting minute amounts of mass loadings on a quartz crystal -- offers utility as highly sensitive detector of fine particles suspended in air. When combined with suitable air delivery system, it provides immediate information on the size distribution and mass concentrations of aerosols. William Chiang, obtained a NASA license for multiple crystal oscillator technology, and initially developed a particle analyzer for NASA use with Langley Research Center assistance. Later his company produced the modified PC-2 for commercial applications Brunswick Corporation uses the device for atmospheric research and in studies of smoke particles in Fires. PC-2 is used by pharmaceutical and chemical companies in research on inhalation toxicology and environmental health. Also useful in testing various filters for safety masks and nuclear installations.

  1. Genetic diversity of Centella asiatica in China analyzed by inter-simple sequence repeat (ISSR) markers: combination analysis with chemical diversity.

    PubMed

    Zhang, Xiao-Gang; Han, Ting; He, Zhi-Gao; Zhang, Qiao-Yan; Zhang, Lei; Rahman, Khalid; Qin, Lu-Ping

    2012-01-01

    Centella asiatica is an important plant species used in traditional Chinese medicine. To help the efficient use and conservation of this species, the genetic diversity of C. asiatica populations in China was investigated using inter-simple sequence repeat (ISSR) markers. Fourteen natural populations comprising 162 individuals were included to estimate genetic diversity. At the species level, genetic diversity was relatively high (P = 66.33%, H = 0.2183, I = 0.3305). At the population level, the genetic diversity of JH (Jinhua, Zhejiang Province, China) and JJ (Jiujiang, Jiangxi Province, China) populations was relatively high (P = 43.88%, 38.78%, H = 0.1610, 0.1301, I = 0.2376, 0.1957, respectively), whereas the genetic diversity of GA (Guang'an, Sichuan Province, China) and EM (E'mei, Sichuan Province, China) was relatively low (P = 10.2%, 5.1%, H = 0.0383, 0.0211, I = 0.0570, 0.0309, respectively). On the basis of Nei's G(st) value, more genetic differentiation among populations was determined (G(st) = 0.6573). In addition, the 14 populations were clustered into four groups in view of abundant ISSR data, which further defined the genetic relationship among populations. Interestingly, the genetic clustering result was similar to previous chemical clustering results based on high-performance liquid chromatography (HPLC) data, which would also classify the 14 populations into four groups. Thus, we combined the clustering results and compared their difference. The combined analysis and genetic diversity data provide a scientific basis for conserving populations of relatively high genetic diversity such as JH and JJ populations and establishing good agricultural practices (GAP) for C. asiatica.

  2. Multiple-tracer gas analyzer

    SciTech Connect

    Uhl, J.E.

    1982-01-01

    A multi-gas tracer system has been designed, built, and used on an explosively fractured oil shale rubble bed. This paper deals exclusively with the hardware, software, and overall operation of the tracer system. This system is a field portable, self-contained unit, which utilizes a mass spectrometer for gas analysis. The unit has a 20 channel sample port capability and is controlled by a desk top computer. The system is configured to provide a dynamic sensitivity range of up to six orders of magnitude. A roots blower is manifolded to the unit to provide continuous flow in all sample lines. The continuous flow process allows representative samples as well as decreasing the time between each measurement. Typical multiplex cycle time to evaluate four unique gases is approximately 12 seconds.

  3. Identification of QTLs of resistance to white mold in common bean from multiple markers by using Bayesian analysis.

    PubMed

    Lara, L A C; Santos, J B; Balestre, M; Lima, I A; Pamplona, A K A; Veloso, J S; Silva, P H

    2015-02-06

    In this study, we identified simple sequence repeat, ampli-fied fragment length polymorphism, and sequence-related amplified poly-morphism markers linked to quantitative trait loci (QTLs) for resistance to white mold disease in common bean progenies derived from a cross between lines CNFC 9506 and RP-2, evaluated using the oxalic acid test and using Bayesian analysis. DNA was extracted from 186 F₂ plants and their parental lines for molecular analysis. Fifteen experiments were car-ried out for phenotypic analysis, which included 186 F₂:₄ progenies, the F₁ generation, the F₂ generation, and the lines CNFC 9506, RP-2, and G122 as common treatments. A completely randomized experimental design with 3 replications was used in controlled environments. The adjusted means for the F₂:₄ generation were to identify QTLs by Bayesian shrink-age analysis. Significant differences were observed among the progenies for the reaction to white mold. The moving away method under the Bayes-ian approach was effective for identifying QTLs when it was not possible to obtain a genetic map because of low marker density. Using the Wald test, 25 markers identified QTLs for resistance to white mold, as well as 16 simple sequence repeats, 7 amplified fragment length polymorphisms, and 2 sequence-related amplified polymorphisms. The markers BM184, BM211, and PV-gaat001 showed low distances from QTLs related white mold resistance. In addition, these markers showed, signal effects with increasing resistance to white mold and high heritability in the analysis with oxalic acid, and thus, are promising for marker-assisted selection.

  4. Short Communication: A Low-Cost Method for Analyzing Nevirapine Levels in Hair as a Marker of Adherence in Resource-Limited Settings

    PubMed Central

    Yang, Qiyun; Bacchetti, Peter; Huang, Yong

    2014-01-01

    Abstract The measurement of antiretroviral concentrations in hair is emerging as an important technology to objectively quantify adherence to combination antiretroviral therapy. Hair levels of antiretrovirals are the strongest independent predictor of virologic success in large prospective cohorts of HIV-infected patients and surpass self-report in predicting outcomes. Hair is easy to collect and store, but validated methods to analyze antiretroviral levels in hair using liquid chromatography tandem mass spectrometry (LC-MS/MS) are expensive. We report here on the development of a thin-layer chromatography (TLC) assay for the semiquantitative analysis of nevirapine in hair. TLC assay results from 11 samples were consistent with results using LC-MS/MS [Spearman correlation coefficient 0.99 (95% CI 0.95–0.996)]. This simple, low-cost method of analyzing nevirapine concentrations in hair may provide a novel monitoring tool for antiretroviral adherence in resource-limited settings and merits further study in clinical settings. PMID:24164410

  5. A SPR biosensor based on signal amplification using antibody-QD conjugates for quantitative determination of multiple tumor markers

    PubMed Central

    Wang, Huan; Wang, Xiaomei; Wang, Jue; Fu, Weiling; Yao, Chunyan

    2016-01-01

    The detection of tumor markers is very important in early cancer diagnosis; however, tumor markers are usually present at very low concentrations, especially in the early stages of tumor development. Surface plasmon resonance (SPR) is widely used to detect biomolecular interactions; it has inherent advantages of being high-throughput, real-time, and label-free technique. However, its sensitivity needs essential improvement for practical applications. In this study, we developed a signal amplification strategy using antibody-quantum dot (QD) conjugates for the sensitive and quantitative detection of α-fetoprotein (AFP), carcinoembryonic antigen (CEA) and cytokeratin fragment 21-1 (CYFRA 21-1) in clinical samples. The use of a dual signal amplification strategy using AuNP-antibody and antibody-QD conjugates increased the signal amplification by 50-folds. The constructed SPR biosensor showed a detection limit as low as 0.1 ng/mL for AFP, CEA, and CYFRA 21-1. Moreover, the results obtained using this SPR biosensor were consistent with those obtained using the electrochemiluminescence method. Thus, the constructed SPR biosensor provides a highly sensitive and specific approach for the detection of tumor markers. This SPR biosensor can be expected to be readily applied for the detection of other tumor markers and can offer a potentially powerful solution for tumor screening. PMID:27615417

  6. The use of regression analysis in determining reference intervals for low hematocrit and thrombocyte count in multiple electrode aggregometry and platelet function analyzer 100 testing of platelet function.

    PubMed

    Kuiper, Gerhardus J A J M; Houben, Rik; Wetzels, Rick J H; Verhezen, Paul W M; van Oerle, Rene; Ten Cate, Hugo; Henskens, Yvonne M C; Lancé, Marcus D

    2017-01-09

    Low platelet counts and hematocrit levels hinder whole blood point-of-care testing of platelet function. Thus far, no reference ranges for MEA (multiple electrode aggregometry) and PFA-100 (platelet function analyzer 100) devices exist for low ranges. Through dilution methods of volunteer whole blood, platelet function at low ranges of platelet count and hematocrit levels was assessed on MEA for four agonists and for PFA-100 in two cartridges. Using (multiple) regression analysis, 95% reference intervals were computed for these low ranges. Low platelet counts affected MEA in a positive correlation (all agonists showed r(2) ≥ 0.75) and PFA-100 in an inverse correlation (closure times were prolonged with lower platelet counts). Lowered hematocrit did not affect MEA testing, except for arachidonic acid activation (ASPI), which showed a weak positive correlation (r(2) = 0.14). Closure time on PFA-100 testing was inversely correlated with hematocrit for both cartridges. Regression analysis revealed different 95% reference intervals in comparison with originally established intervals for both MEA and PFA-100 in low platelet or hematocrit conditions. Multiple regression analysis of ASPI and both tests on the PFA-100 for combined low platelet and hematocrit conditions revealed that only PFA-100 testing should be adjusted for both thrombocytopenia and anemia. 95% reference intervals were calculated using multiple regression analysis. However, coefficients of determination of PFA-100 were poor, and some variance remained unexplained. Thus, in this pilot study using (multiple) regression analysis, we could establish reference intervals of platelet function in anemia and thrombocytopenia conditions on PFA-100 and in thrombocytopenia conditions on MEA.

  7. DNA isolation from teeth by organic extraction and identification of sex of the individual by analyzing the AMEL gene marker using PCR

    PubMed Central

    Praveen Kumar, Subramanian Thangaraj; Aswath, Nalini

    2016-01-01

    Background: To identify the sex of the deceased individual from dental hard tissue such as enamel and dentine. Objective: To isolate the DNA from dental hard tissue (enamel and dentin) from teeth extracted for prophylactic purpose, to assess the quality and purity of DNA and to identify the sex using polymerized chain reactor (PCR). Materials and Methods: DNA was extracted following phenol/chloroform (organic) extraction from 20 male and 20 female teeth. The samples that contain the amelogenin gene (amel) were amplified by PCR. The products of the PCR were run on agarose gel with ethidium bromide staining on gel documentation system. Results: The results on the gel showed the presence of X-specific bands at 212 bp and Y-specific bands at 218 bp. Males were distinguished from females by the presence of two bands whereas female samples showed only one, that is, X-specific band on the gel. The gender from the known samples was determined with complete accuracy, and the results were analyzed statistically by the Chi-square test. Conclusion: In our study, the PCR-based method showed 100% specificity and sensitivity. PMID:27051218

  8. A new set of rDNA-NTS-based multiple integrative cassettes for the development of antibiotic-marker-free recombinant yeasts.

    PubMed

    Moon, Hye Yun; Lee, Dong Wook; Sim, Gyu Hun; Kim, Hong-Jin; Hwang, Jee Youn; Kwon, Mun-Gyeong; Kang, Bo-Kyu; Kim, Jong Man; Kang, Hyun Ah

    2016-09-10

    The traditional yeast Saccharomyces cerevisiae has been widely used as a host system to produce recombinant proteins and metabolites of great commercial value. To engineer recombinant yeast that stably maintains expression cassettes without an antibiotic resistance gene, we developed new multiple integration cassettes by exploiting the non-transcribed spacer (NTS) of ribosomal DNA (rDNA) in combination with defective selection markers. The 5' and 3'-fragments of rDNA-NTS2 were used as flanking sequences for the expression cassettes carrying a set of URA3, LEU2, HIS3, and TRP1 selection markers with truncated promoters of different lengths. The integration numbers of NTS-based expression cassettes, ranging from one to ∼30 copies, showed a proportional increase with the extent of decreased expression of the auxotrophic markers. The NTS-based cassettes were used to construct yeast strains expressing the capsid protein of red-spotted grouper necrosis virus (RG-NNVCP) in a copy number-dependent manner. Oral administration of the recombinant yeast, harboring ∼30 copies of the integrated RG-NNVCP cassettes, provoked efficient immune responses in mice. In contrast, for the NTS cassettes expressing a truncated 3-hydroxyl-3-methylglutaryl-CoA reductase, the integrant carrying only 4 copies was screened as the highest producer of squalene, showing a 150-fold increase compared to that of the wild-type strain. The multiple integrated cassettes were stably retained under prolonged nonselective conditions. Altogether, our results strongly support that rDNA-NTS integrative cassettes are useful tools to construct recombinant yeasts carrying optimal copies of a desired expression cassette without an antibiotic marker gene, which are suitable as oral vaccines or feed additives for animal and human consumption.

  9. Altered expression of oligodendrocyte and neuronal marker genes predicts the clinical onset of autoimmune encephalomyelitis and indicates the effectiveness of multiple sclerosis-directed therapeutics.

    PubMed

    Evangelidou, Maria; Karamita, Maria; Vamvakas, Sotiris-Spyros; Szymkowski, David E; Probert, Lesley

    2014-05-01

    Experimental autoimmune encephalomyelitis (EAE) is a valuable model for studying immunopathology in multiple sclerosis (MS) and for exploring the interface between autoimmune responses and CNS tissue that ultimately leads to lesion development. In this study, we measured gene expression in mouse spinal cord during myelin oligodendrocyte gp35-55 peptide-induced EAE, using quantitative RT-PCR, to identify gene markers that monitor individual hallmark pathological processes. We defined a small panel of genes whose longitudinal expression patterns provided insight into the timing, interrelationships, and mechanisms of individual disease processes and the efficacy of therapeutics for the treatment of MS. Earliest transcriptional changes were upregulation of Il17a and sharp downregulation of neuronal and oligodendrocyte marker genes preceding clinical disease onset, whereas neuroinflammatory markers progressively increased as symptoms and tissue lesions developed. EAE-induced gene-expression changes were not altered in mice deficient in IKKβ in cells of the myeloid lineage compared with controls, but the administration of a selective inhibitor of soluble TNF to mice from the day of immunization delayed changes in the expression of innate inflammation, myelin, and neuron markers from the presymptomatic phase. Proof of principle that the gene panel shows drug screening potential was obtained using a well-established MS therapeutic, glatiramer acetate. Prophylactic treatment of mice with glatiramer acetate normalized gene marker expression, and this correlated with the level of therapeutic success. These results show that neurons and oligodendrocytes are highly sensitive to CNS-directed autoimmunity before the development of clinical symptoms and immunopathology and reveal a role for soluble TNF in mediating the earliest changes in gene expression.

  10. Concept and simulation study of a novel localization method for robotic endoscopic capsules using multiple positron emission markers

    SciTech Connect

    Than, Trung Duc Alici, Gursel Zhou, Hao Li, Weihua; Harvey, Steven

    2014-07-15

    Purpose: Over the last decade, wireless capsule endoscope has been the tool of choice for noninvasive inspection of the gastrointestinal tract, especially in the small intestine. However, the latest clinical products have not been equipped with a sufficiently accurate localization system which makes it difficult to determine the location of intestinal abnormalities, and to apply follow-up interventions such as biopsy or drug delivery. In this paper, the authors present a novel localization method based on tracking three positron emission markers embedded inside an endoscopic capsule. Methods: Three spherical {sup 22}Na markers with diameters of less than 1 mm are embedded in the cover of the capsule. Gamma ray detectors are arranged around a patient body to detect coincidence gamma rays emitted from the three markers. The position of each marker can then be estimated using the collected data by the authors’ tracking algorithm which consists of four consecutive steps: a method to remove corrupted data, an initialization method, a clustering method based on the Fuzzy C-means clustering algorithm, and a failure prediction method. Results: The tracking algorithm has been implemented inMATLAB utilizing simulation data generated from the Geant4 Application for Emission Tomography toolkit. The results show that this localization method can achieve real-time tracking with an average position error of less than 0.4 mm and an average orientation error of less than 2°. Conclusions: The authors conclude that this study has proven the feasibility and potential of the proposed technique in effectively determining the position and orientation of a robotic endoscopic capsule.

  11. A fuzzy integral method based on the ensemble of neural networks to analyze fMRI data for cognitive state classification across multiple subjects.

    PubMed

    Cacha, L A; Parida, S; Dehuri, S; Cho, S-B; Poznanski, R R

    2016-12-01

    The huge number of voxels in fMRI over time poses a major challenge to for effective analysis. Fast, accurate, and reliable classifiers are required for estimating the decoding accuracy of brain activities. Although machine-learning classifiers seem promising, individual classifiers have their own limitations. To address this limitation, the present paper proposes a method based on the ensemble of neural networks to analyze fMRI data for cognitive state classification for application across multiple subjects. Similarly, the fuzzy integral (FI) approach has been employed as an efficient tool for combining different classifiers. The FI approach led to the development of a classifiers ensemble technique that performs better than any of the single classifier by reducing the misclassification, the bias, and the variance. The proposed method successfully classified the different cognitive states for multiple subjects with high accuracy of classification. Comparison of the performance improvement, while applying ensemble neural networks method, vs. that of the individual neural network strongly points toward the usefulness of the proposed method.

  12. Anti-Epstein-Barr virus antibodies as serological markers of multiple sclerosis: a prospective study among United States military personnel

    PubMed Central

    Munger, K. L.; Levin, L. I.; O’Reilly, E. J.; Falk, K. I.; Ascherio, A.

    2011-01-01

    Background Elevated Epstein-Barr virus (EBV) antibody titers are risk factors for MS, but the strength and consistency this association are not well characterized. Objectives To determine whether this association is confounded by vitamin D or modified by gender or race, and the usefulness of EBV nuclear antigen (EBNA) antibodies as a marker for MS. Methods We conducted a prospective study among US military personnel. Antibody titers against EBV antigens were measured in serum samples from 222 individuals who developed MS and 444 age, sex, and race/ethnicity matched controls. Conditional logistic regression was used to estimate relative risks. Results MS risk increased with increasing titers of anti-EBNA complex (p<10−9) and anti-EBNA-1 (p=5.8E-9) titers. MS risk was 36-fold higher among individuals with anti-EBNA complex IgG titers ≥320 than among those with titers <20 (95%CI:9.6-136), and 8-fold higher among those with anti-EBNA-1 ≥320 than among those with anti-EBNA-1 <20 (95%CI:2.6-23). These associations were consistent across gender and race/ethnicity groups and independent from 25-hydroxyvitamin D levels. Areas under the ROC curves were 0.67 for EBNA complex and 0.65 for EBNA-1. Conclusions Serum titers of pre-onset anti-EBNA antibodies are strong, robust markers of MS risk and could be useful in an MS risk score. PMID:21685232

  13. Using multiple markers to elucidate the ancient, historical and modern relationships among North American Arctic dog breeds

    PubMed Central

    Brown, S K; Darwent, C M; Wictum, E J; Sacks, B N

    2015-01-01

    Throughout most of the Americas, post-colonial dogs largely erased the genetic signatures of pre-historical dogs. However, the North American Arctic harbors dogs that are potentially descended from pre-historical ancestors, as well as those affected by post-colonial translocations and admixtures. In particular, Inuit dogs from Canada and Greenland are thought to descend from dogs associated with Thule peoples, who relied on them for transportation ca. 1000 years ago. Whether Thule dogs reflected an earlier colonization by Paleoeskimo dogs ca. 4500 years ago is unknown. During the Alaskan Gold Rush, additional sled dogs, possibly of post-colonial derivation, the Alaskan Husky, Malamute and Siberian Husky, were used in the Arctic. The genealogical relationships among and origins of these breeds are unknown. Here we use autosomal, paternal and maternal DNA markers to (1) test the hypothesis that Inuit dogs have retained their indigenous ancestry, (2) characterize their relationship to one another and to other Arctic breeds, and (3) estimate the age of North American indigenous matrilines and patrilines. On the basis of the agreement of all three markers we determined that Inuit dogs have maintained their indigenous nature, and that they likely derive from Thule dogs. In addition, we provide support for previous research that the Inuit dogs from Canada and Greenland dog should not be distinguished as two breeds. The Alaskan Husky displayed evidence of European introgression, in contrast to the Malamute and Siberian Husky, which appear to have maintained most of their ancient Siberian ancestry. PMID:26103948

  14. Using multiple markers to elucidate the ancient, historical and modern relationships among North American Arctic dog breeds.

    PubMed

    Brown, S K; Darwent, C M; Wictum, E J; Sacks, B N

    2015-12-01

    Throughout most of the Americas, post-colonial dogs largely erased the genetic signatures of pre-historical dogs. However, the North American Arctic harbors dogs that are potentially descended from pre-historical ancestors, as well as those affected by post-colonial translocations and admixtures. In particular, Inuit dogs from Canada and Greenland are thought to descend from dogs associated with Thule peoples, who relied on them for transportation ca. 1000 years ago. Whether Thule dogs reflected an earlier colonization by Paleoeskimo dogs ca. 4500 years ago is unknown. During the Alaskan Gold Rush, additional sled dogs, possibly of post-colonial derivation, the Alaskan Husky, Malamute and Siberian Husky, were used in the Arctic. The genealogical relationships among and origins of these breeds are unknown. Here we use autosomal, paternal and maternal DNA markers to (1) test the hypothesis that Inuit dogs have retained their indigenous ancestry, (2) characterize their relationship to one another and to other Arctic breeds, and (3) estimate the age of North American indigenous matrilines and patrilines. On the basis of the agreement of all three markers we determined that Inuit dogs have maintained their indigenous nature, and that they likely derive from Thule dogs. In addition, we provide support for previous research that the Inuit dogs from Canada and Greenland dog should not be distinguished as two breeds. The Alaskan Husky displayed evidence of European introgression, in contrast to the Malamute and Siberian Husky, which appear to have maintained most of their ancient Siberian ancestry.

  15. Comprehensive peptide marker identification for the detection of multiple nut allergens using a non-targeted LC-HRMS multi-method.

    PubMed

    Korte, Robin; Lepski, Silke; Brockmeyer, Jens

    2016-05-01

    Food allergies have emerged as a global problem over the last few decades; therefore, reliable and sensitive analytical methods to ensure food safety for allergic consumers are required. The application of mass spectrometry is of growing interest in this field and several procedures based on low resolution tandem mass spectrometry using single tryptic peptides as analytical targets have recently been described. However, a comprehensive survey of marker peptides for the development of multi-methods is still missing, as is a consensus guide to marker identification. In this study, we therefore report a consistent approach to the development of liquid chromatography-mass spectrometry (LC-MS) multi-screening methods for the detection of allergens in food matrices. Proteotypic peptides were identified by a shotgun proteomics approach and verified through a thorough investigation of specificity and sensitivity. On the basis of this procedure, we identified 44 suitable tryptic marker peptides from six allergenic nut species and developed the first analytical LC-MS method for the detection of trace nut contaminations in processed foods using high resolution mass spectrometry (HRMS). The analysis of spiked matrix samples gave limits of detection (LODs) below 10 μg/g for several nuts; these LODs are comparable with routinely used methods such as ELISA and PCR. Notably, the HRMS approach can be used in an untargeted fashion to identify multiple allergens also retrospectively. In conclusion, we present here the so far largest consensus set of analytical markers from nut allergens and to the best of our knowledge the first multi-allergen method based on LC-HRMS.

  16. Distinctive mitochondrial genome of Calanoid copepod Calanus sinicus with multiple large non-coding regions and reshuffled gene order: Useful molecular markers for phylogenetic and population studies

    PubMed Central

    2011-01-01

    Background Copepods are highly diverse and abundant, resulting in extensive ecological radiation in marine ecosystems. Calanus sinicus dominates continental shelf waters in the northwest Pacific Ocean and plays an important role in the local ecosystem by linking primary production to higher trophic levels. A lack of effective molecular markers has hindered phylogenetic and population genetic studies concerning copepods. As they are genome-level informative, mitochondrial DNA sequences can be used as markers for population genetic studies and phylogenetic studies. Results The mitochondrial genome of C. sinicus is distinct from other arthropods owing to the concurrence of multiple non-coding regions and a reshuffled gene arrangement. Further particularities in the mitogenome of C. sinicus include low A + T-content, symmetrical nucleotide composition between strands, abbreviated stop codons for several PCGs and extended lengths of the genes atp6 and atp8 relative to other copepods. The monophyletic Copepoda should be placed within the Vericrustacea. The close affinity between Cyclopoida and Poecilostomatoida suggests reassigning the latter as subordinate to the former. Monophyly of Maxillopoda is rejected. Within the alignment of 11 C. sinicus mitogenomes, there are 397 variable sites harbouring three 'hotspot' variable sites and three microsatellite loci. Conclusion The occurrence of the circular subgenomic fragment during laboratory assays suggests that special caution should be taken when sequencing mitogenomes using long PCR. Such a phenomenon may provide additional evidence of mitochondrial DNA recombination, which appears to have been a prerequisite for shaping the present mitochondrial profile of C. sinicus during its evolution. The lack of synapomorphic gene arrangements among copepods has cast doubt on the utility of gene order as a useful molecular marker for deep phylogenetic analysis. However, mitochondrial genomic sequences have been valuable markers for

  17. Empirical comparison of methods for analyzing multiple time-to-event outcomes in a non-inferiority trial: a breast cancer study

    PubMed Central

    2013-01-01

    Background Subjects with breast cancer enrolled in trials may experience multiple events such as local recurrence, distant recurrence or death. These events are not independent; the occurrence of one may increase the risk of another, or prevent another from occurring. The most commonly used Cox proportional hazards (Cox-PH) model ignores the relationships between events, resulting in a potential impact on the treatment effect and conclusions. The use of statistical methods to analyze multiple time-to-event events has mainly been focused on superiority trials. However, their application to non-inferiority trials is limited. We evaluate four statistical methods for multiple time-to-event endpoints in the context of a non-inferiority trial. Methods Three methods for analyzing multiple events data, namely, i) the competing risks (CR) model, ii) the marginal model, and iii) the frailty model were compared with the Cox-PH model using data from a previously-reported non-inferiority trial comparing hypofractionated radiotherapy with conventional radiotherapy for the prevention of local recurrence in patients with early stage breast cancer who had undergone breast conserving surgery. These methods were also compared using two simulated examples, scenario A where the hazards for distant recurrence and death were higher in the control group, and scenario B. where the hazards of distant recurrence and death were higher in the experimental group. Both scenarios were designed to have a non-inferiority margin of 1.50. Results In the breast cancer trial, the methods produced primary outcome results similar to those using the Cox-PH model: namely, a local recurrence hazard ratio (HR) of 0.95 and a 95% confidence interval (CI) of 0.62 to 1.46. In Scenario A, non-inferiority was observed with the Cox-PH model (HR = 1.04; CI of 0.80 to 1.35), but not with the CR model (HR = 1.37; CI of 1.06 to 1.79), and the average marginal and frailty model showed a positive effect of the

  18. Insights into the phylogeny of sporadotrichid ciliates (Protozoa, Ciliophora: Hypotricha) based on genealogical analyses of multiple molecular markers

    NASA Astrophysics Data System (ADS)

    Hu, Xiaoyan; Hu, Xiaozhong; Al-Rasheid, Khaled A. S.; Al-Farraj, Saleh A.; Song, Weibo

    2011-01-01

    The sporadotrichid ciliates are an especially diverse group. A number of investigators have studied the morphological, morphogenetic, and molecular relationships among members of this group. Despite this, a consistent classification is still lacking and several important questions about the phylogenetic relationships within this group remain unsolved. To improve our understanding of these relationships, we constructed phylogenetic trees using the nucleotide sequences of the small-subunit rRNA (SSrRNA) gene and amino acid sequences of actin I and α-tubulin. Analyses of SSrRNA gene sequences indicated that: 1) the Sporadotrichida sensu Lynn (2008) and the Oxytrichidae are polyphyletic; 2) the Uroleptus species, which are classified to urostylids, formed a sister group with the oxytrichids; 3) Halteria grandinella, which is grouped morphologically with oligotrich species, clustered within the oxytrichids. These results are congruent with previous studies based on SSrRNA gene sequences. However, the amino acid sequences of actin I and α-tubulin yielded different topologies. The main results are: 1) in all phylogenetic trees, the genus Oxytricha was paraphyletic; 2) Uroleptus was sister to a subset of Urostyla and Holosticha, albeit with low supporting values; 3) Halteria grandinella was separated distantly from the Oxytrichidae in trees inferred from actin I amino acid sequences but clustered with oligotrichids in the α-tubulin analysis. The inconsistency among the trees inferred from these different molecular markers may be caused by rapidly accumulated genetic characterizations of ciliates. Further studies with additional molecular markers and sampling of more taxa are expected to better address the relationships among sporadotrichids.

  19. Stereotactic core needle breast biopsy marker migration: An analysis of factors contributing to immediate marker migration.

    PubMed

    Jain, Ashali; Khalid, Maria; Qureshi, Muhammad M; Georgian-Smith, Dianne; Kaplan, Jonah A; Buch, Karen; Grinstaff, Mark W; Hirsch, Ariel E; Hines, Neely L; Anderson, Stephan W; Gallagher, Katherine M; Bates, David D B; Bloch, B Nicolas

    2017-05-19

    To evaluate breast biopsy marker migration in stereotactic core needle biopsy procedures and identify contributing factors. This retrospective study analyzed 268 stereotactic biopsy markers placed in 263 consecutive patients undergoing stereotactic biopsies using 9G vacuum-assisted devices from August 2010-July 2013. Mammograms were reviewed and factors contributing to marker migration were evaluated. Basic descriptive statistics were calculated and comparisons were performed based on radiographically-confirmed marker migration. Of the 268 placed stereotactic biopsy markers, 35 (13.1%) migrated ≥1 cm from their biopsy cavity. Range: 1-6 cm; mean (± SD): 2.35 ± 1.22 cm. Of the 35 migrated biopsy markers, 9 (25.7%) migrated ≥3.5 cm. Patient age, biopsy pathology, number of cores, and left versus right breast were not associated with migration status (P> 0.10). Global fatty breast density (P= 0.025) and biopsy in the inner region of breast (P = 0.031) were associated with marker migration. Superior biopsy approach (P= 0.025), locally heterogeneous breast density, and t-shaped biopsy markers (P= 0.035) were significant for no marker migration. Multiple factors were found to influence marker migration. An overall migration rate of 13% supports endeavors of research groups actively developing new biopsy marker designs for improved resistance to migration. • Breast biopsy marker migration is documented in 13% of 268 procedures. • Marker migration is affected by physical, biological, and pathological factors. • Breast density, marker shape, needle approach etc. affect migration. • Study demonstrates marker migration prevalence; marker design improvements are needed.

  20. Objective markers for sleep propensity: comparison between the Multiple Sleep Latency Test and the Vigilance Algorithm Leipzig.

    PubMed

    Olbrich, Sebastian; Fischer, Marie M; Sander, Christian; Hegerl, Ulrich; Wirtz, Hubert; Bosse-Henck, Andrea

    2015-08-01

    The regulation of wakefulness is important for high-order organisms. Its dysregulation is involved in the pathomechanism of several psychiatric disorders. Thus, a tool for its objective but little time-consuming assessment would be of importance. The Vigilance Algorithm Leipzig allows the objective measurement of sleep propensity, based on a single resting state electroencephalogram. To compare the Vigilance Algorithm Leipzig with the standard for objective assessment of excessive daytime sleepiness, a four-trial Multiple Sleep Latency Test in 25 healthy subjects was conducted. Between the first two trials, a 15-min, 25-channel resting electroencephalogram was recorded, and Vigilance Algorithm Leipzig was used to classify the sleep propensity (i.e., type of vigilance regulation) of each subject. The results of both methods showed significant correlations with the Epworth Sleepiness Scale (ρ = -0.70; ρ = 0.45, respectively) and correlated with each other (ρ = -0.54). Subjects with a stable electroencephalogram-vigilance regulation yielded significant increased sleep latencies compared with an unstable regulation (multiple sleep latency 898.5 s versus 549.9 s; P = 0.03). Further, Vigilance Algorithm Leipzig classifications allowed the identification of subjects with average sleep latencies <6 min with a sensitivity of 100% and a specificity of 77%. Thus, Vigilance Algorithm Leipzig provides similar information on wakefulness regulation in comparison to the much more cost- and time-consuming Multiple Sleep Latency Test. Due to its high sensitivity and specificity for large sleep propensity, Vigilance Algorithm Leipzig could be an effective and reliable alternative to the Multiple Sleep Latency Test, for example for screening purposes in large cohorts, where objective information about wakefulness regulation is needed.

  1. Use of Multiple Metabolic and Genetic Markers to Improve the Prediction of Type 2 Diabetes: the EPIC-Potsdam Study

    PubMed Central

    Schulze, Matthias B.; Weikert, Cornelia; Pischon, Tobias; Bergmann, Manuela M.; Al-Hasani, Hadi; Schleicher, Erwin; Fritsche, Andreas; Häring, Hans-Ulrich; Boeing, Heiner; Joost, Hans-Georg

    2009-01-01

    OBJECTIVE We investigated whether metabolic biomarkers and single nucleotide polymorphisms (SNPs) improve diabetes prediction beyond age, anthropometry, and lifestyle risk factors. RESEARCH DESIGN AND METHODS A case-cohort study within a prospective study was designed. We randomly selected a subcohort (n = 2,500) from 26,444 participants, of whom 1,962 were diabetes free at baseline. Of the 801 incident type 2 diabetes cases identified in the cohort during 7 years of follow-up, 579 remained for analyses after exclusions. Prediction models were compared by receiver operatoring characteristic (ROC) curve and integrated discrimination improvement. RESULTS Case-control discrimination by the lifestyle characteristics (ROC-AUC: 0.8465) improved with plasma glucose (ROC-AUC: 0.8672, P < 0.001) and A1C (ROC-AUC: 0.8859, P < 0.001). ROC-AUC further improved with HDL cholesterol, triglycerides, γ-glutamyltransferase, and alanine aminotransferase (0.9000, P = 0.002). Twenty SNPs did not improve discrimination beyond these characteristics (P = 0.69). CONCLUSIONS Metabolic markers, but not genotyping for 20 diabetogenic SNPs, improve discrimination of incident type 2 diabetes beyond lifestyle risk factors. PMID:19720844

  2. Use of multiple markers for investigation of an epidemic of Shigella sonnei infections in Monroe County, New York.

    PubMed Central

    Yagupsky, P; Loeffelholz, M; Bell, K; Menegus, M A

    1991-01-01

    Antibiotic susceptibility patterns, plasmid profiles, and endonuclease restriction analysis of plasmid DNA were used in the investigation of an epidemic of Shigella sonnei infections in Monroe County, New York, in 1988 and 1989. The epidemic peaked during the winter, included the simultaneous transmission of the disease from person to person and from common food sources, and especially affected inhabitants of the poor, inner-city neighborhoods, young children of both sexes, and women. Resistance to ampicillin, tetracycline, or trimethoprim-sulfamethoxazole, encoded in a 70-MDa plasmid, was found in most of the examined isolates. Unexpectedly, isolates from patients involved in a food-borne outbreak exhibited three different antibiotic susceptibility patterns, suggesting deletion of antibiotic resistance determinants in some strains. Antibiograms clearly separated food-borne outbreak-related and non-foodborne outbreak-related strains, distinguished more strains than did the plasmid profiles, and were useful in tracing the dissemination of individual isolates in the community. Restriction endonuclease analysis substantially increased the discriminatory value of plasmid profiles and validated the antibiogram results. The present study illustrates the complexity of epidemics of S. sonnei infections and shows the value of combining different biological markers in the investigation. Images PMID:1757559

  3. Managing Multiple Mandates: A System of Systems Model to Analyze Strategies for Producing Cellulosic Ethanol and Reducing Riverine Nitrate Loads in the Upper Mississippi River Basin.

    PubMed

    Housh, Mashor; Yaeger, Mary A; Cai, Ximing; McIsaac, Gregory F; Khanna, Madhu; Sivapalan, Murugesu; Ouyang, Yanfeng; Al-Qadi, Imad; Jain, Atul K

    2015-10-06

    Implementing public policies often involves navigating an array of choices that have economic and environmental consequences that are difficult to quantify due to the complexity of multiple system interactions. Implementing the mandate for cellulosic biofuel production in the Renewable Fuel Standard (RFS) and reducing hypoxia in the northern Gulf of Mexico by reducing riverine nitrate-N loads represent two such cases that overlap in the Mississippi River Basin. To quantify the consequences of these interactions, a system of systems (SoS) model was developed that incorporates interdependencies among the various subsystems, including biofuel refineries, transportation, agriculture, water resources and crop/ethanol markets. The model allows examination of the impact of imposing riverine nitrate-N load limits on the biofuel production system as a whole, including land use change and infrastructure needs. The synergies of crop choice (first versus second generation biofuel crops), infrastructure development, and environmental impacts (streamflow and nitrate-N load) were analyzed to determine the complementarities and trade-offs between environmental protection and biofuel development objectives. For example, the results show that meeting the cellulosic biofuel target in the RFS using Miscanthus x giganteus reduces system profits by 8% and reduces nitrate-N loads by 12% compared to the scenario without a mandate. However, greater water consumption by Miscanthus is likely to reduce streamflow with potentially adverse environmental consequences that need to be considered in future decision making.

  4. Phylogenetic Reconstruction and DNA Barcoding for Closely Related Pine Moth Species (Dendrolimus) in China with Multiple Gene Markers

    PubMed Central

    Dai, Qing-Yan; Gao, Qiang; Wu, Chun-Sheng; Chesters, Douglas; Zhu, Chao-Dong; Zhang, Ai-Bing

    2012-01-01

    Unlike distinct species, closely related species offer a great challenge for phylogeny reconstruction and species identification with DNA barcoding due to their often overlapping genetic variation. We tested a sibling species group of pine moth pests in China with a standard cytochrome c oxidase subunit I (COI) gene and two alternative internal transcribed spacer (ITS) genes (ITS1 and ITS2). Five different phylogenetic/DNA barcoding analysis methods (Maximum likelihood (ML)/Neighbor-joining (NJ), “best close match” (BCM), Minimum distance (MD), and BP-based method (BP)), representing commonly used methodology (tree-based and non-tree based) in the field, were applied to both single-gene and multiple-gene analyses. Our results demonstrated clear reciprocal species monophyly for three relatively distant related species, Dendrolimus superans, D. houi, D. kikuchii, as recovered by both single and multiple genes while the phylogenetic relationship of three closely related species, D. punctatus, D. tabulaeformis, D. spectabilis, could not be resolved with the traditional tree-building methods. Additionally, we find the standard COI barcode outperforms two nuclear ITS genes, whatever the methods used. On average, the COI barcode achieved a success rate of 94.10–97.40%, while ITS1 and ITS2 obtained a success rate of 64.70–81.60%, indicating ITS genes are less suitable for species identification in this case. We propose the use of an overall success rate of species identification that takes both sequencing success and assignation success into account, since species identification success rates with multiple-gene barcoding system were generally overestimated, especially by tree-based methods, where only successfully sequenced DNA sequences were used to construct a phylogenetic tree. Non-tree based methods, such as MD, BCM, and BP approaches, presented advantages over tree-based methods by reporting the overall success rates with statistical significance. In addition

  5. Phylogenetic reconstruction and DNA barcoding for closely related pine moth species (Dendrolimus) in China with multiple gene markers.

    PubMed

    Dai, Qing-Yan; Gao, Qiang; Wu, Chun-Sheng; Chesters, Douglas; Zhu, Chao-Dong; Zhang, Ai-Bing

    2012-01-01

    Unlike distinct species, closely related species offer a great challenge for phylogeny reconstruction and species identification with DNA barcoding due to their often overlapping genetic variation. We tested a sibling species group of pine moth pests in China with a standard cytochrome c oxidase subunit I (COI) gene and two alternative internal transcribed spacer (ITS) genes (ITS1 and ITS2). Five different phylogenetic/DNA barcoding analysis methods (Maximum likelihood (ML)/Neighbor-joining (NJ), "best close match" (BCM), Minimum distance (MD), and BP-based method (BP)), representing commonly used methodology (tree-based and non-tree based) in the field, were applied to both single-gene and multiple-gene analyses. Our results demonstrated clear reciprocal species monophyly for three relatively distant related species, Dendrolimus superans, D. houi, D. kikuchii, as recovered by both single and multiple genes while the phylogenetic relationship of three closely related species, D. punctatus, D. tabulaeformis, D. spectabilis, could not be resolved with the traditional tree-building methods. Additionally, we find the standard COI barcode outperforms two nuclear ITS genes, whatever the methods used. On average, the COI barcode achieved a success rate of 94.10-97.40%, while ITS1 and ITS2 obtained a success rate of 64.70-81.60%, indicating ITS genes are less suitable for species identification in this case. We propose the use of an overall success rate of species identification that takes both sequencing success and assignation success into account, since species identification success rates with multiple-gene barcoding system were generally overestimated, especially by tree-based methods, where only successfully sequenced DNA sequences were used to construct a phylogenetic tree. Non-tree based methods, such as MD, BCM, and BP approaches, presented advantages over tree-based methods by reporting the overall success rates with statistical significance. In addition, our

  6. Composite Marker of Cognitive Dysfunction and Brain Atrophy is Highly Accurate in Discriminating Between Relapsing-Remitting and Secondary Progressive Multiple Sclerosis

    PubMed Central

    Kizlaitienandedot, Rasa; Kaubrys, Gintaras; Giedraitienandedot, Nataandscaron;a; Ramanauskas, Naglis; Dementaviandccaron;ienandedot;, Jūratandedot;

    2017-01-01

    Background With the advent of numerous new-generation disease-modifying drugs for multiple sclerosis (MS), the discrimination between relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) has become a problem of high importance. The aim of our study was to find a simple way to accurately discriminate between RRMS and SPMS that is applicable in clinical practice as a composite marker, using the linear measures of magnetic resonance imaging (MRI) and the results of cognitive tests. Material/Methods We included 88 MS patients in the study: 43 participants had RRMS and 45 had SPMS. A battery consisting of 11 tests was used to evaluate cognitive function. We used 11 linear MRI measures and 7 indexes to assess brain atrophy. Results Four cognitive tests and 3 linear MRI measures were able to distinguish RRMS from SPMS with the AUC >0.8 based on ROC analysis. Multiple logistic regression models were constructed to identify the best set of cognitive and MRI markers. The model, using the Rey Auditory Verbal Learning Test (RAVLT), Digit Symbol Substitution Test (DSST), and Huckman Index, showed the highest predictive ability: AUC=0.921 (p<0.001). We constructed a simple remission-progression index from the same 3 variables, which discriminated well between RRMS and SPMS: AUC=0.920 (p<0.001), maximal Youden Index=0.702, cut-off=1.68, sensitivity=79.1%, and specificity=91.1%. Conclusions The composite remission-progression index, using the RAVLT test, DSST test, and MRI Huckman Index, is highly accurate in discriminating between RRMS and SPMS. PMID:28145395

  7. Composite Marker of Cognitive Dysfunction and Brain Atrophy is Highly Accurate in Discriminating Between Relapsing-Remitting and Secondary Progressive Multiple Sclerosis.

    PubMed

    Kizlaitienė, Rasa; Kaubrys, Gintaras; Giedraitienė, Nataša; Ramanauskas, Naglis; Dementavičienė, Jūratė

    2017-02-01

    BACKGROUND With the advent of numerous new-generation disease-modifying drugs for multiple sclerosis (MS), the discrimination between relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) has become a problem of high importance. The aim of our study was to find a simple way to accurately discriminate between RRMS and SPMS that is applicable in clinical practice as a composite marker, using the linear measures of magnetic resonance imaging (MRI) and the results of cognitive tests. MATERIAL AND METHODS We included 88 MS patients in the study: 43 participants had RRMS and 45 had SPMS. A battery consisting of 11 tests was used to evaluate cognitive function. We used 11 linear MRI measures and 7 indexes to assess brain atrophy. RESULTS Four cognitive tests and 3 linear MRI measures were able to distinguish RRMS from SPMS with the AUC >0.8 based on ROC analysis. Multiple logistic regression models were constructed to identify the best set of cognitive and MRI markers. The model, using the Rey Auditory Verbal Learning Test (RAVLT), Digit Symbol Substitution Test (DSST), and Huckman Index, showed the highest predictive ability: AUC=0.921 (p<0.001). We constructed a simple remission-progression index from the same 3 variables, which discriminated well between RRMS and SPMS: AUC=0.920 (p<0.001), maximal Youden Index=0.702, cut-off=1.68, sensitivity=79.1%, and specificity=91.1%. CONCLUSIONS The composite remission-progression index, using the RAVLT test, DSST test, and MRI Huckman Index, is highly accurate in discriminating between RRMS and SPMS.

  8. Phylogenetic analysis with multiple markers indicates repeated loss of the adult medusa stage in Campanulariidae (Hydrozoa, Cnidaria).

    PubMed

    Govindarajan, Annette F; Boero, Ferdinando; Halanych, Kenneth M

    2006-03-01

    The Campanulariidae is a group of leptomedusan hydroids (Hydrozoa, Cnidaria) that exhibit a diverse array of life cycles ranging from species with a free medusa stage to those with a reduced or absent medusa stage. Perhaps the best-known member of the taxon is Obelia which is often used as a textbook model of hydrozoan life history. However, Obelia medusae have several unique features leading to a hypothesis that Obelia arose, in a saltational fashion, from an ancestor that lacked a medusa, possibly representing an example of a rare evolutionary reversal. To address the evolution of adult sexual stages in Campanulariidae, a molecular phylogenetic approach was employed using two nuclear (18S rDNA and calmodulin) and two mitochondrial (16S rDNA and cytochrome c oxidase subunit I) genes. Prior to the main analysis, we conducted a preliminary analysis of leptomedusan taxa which suggests that Campanulariidae as presently considered needs to be redefined. Campanulariid analyses are consistent with morphological understanding in that three major clades are recovered. However, several recognized genera are not monophyletic calling into question some "diagnostic" features. Furthermore, ancestral states were reconstructed using parsimony, and a sensitivity analysis was conducted to investigate possible evolutionary transitions in life-history stages. The results indicate that life-cycle transitions have occurred multiple times, and that Obelia might be derived from an ancestor with Clytia-like features.

  9. Multiplicity

    DTIC Science & Technology

    1991-04-01

    practice as a "[descent] into that inner circle of the Inferno where the damned endlessly degate multiplicity for sentencing." United States v. Barnard...select the charges to be brought in a particular case"). 19 Brown v. Ohio, 432 U.S. 161, 165 (1977). 20 Whalen v. United States, 445 U.S. at 689. 21...parte Lange, 8-5 U.S. (19 Wall.) 163 (1874). Cf. Brown v. Ohio, 432 U.S. at 165 ("once the legislature has acted courts may not impose more than one

  10. Qualitative analysis of Psoraleae Fructus by HPLC-DAD/TOF-MS fingerprint and quantitative analysis of multiple components by single marker.

    PubMed

    Luan, Lianjun; Shen, Xiaoyu; Liu, Xuesong; Wu, Yongjiang; Tan, Manliang

    2017-08-04

    A variety of bioactive substances may account for the recognized efficacy and wide clinical application of Psoraleae Fructus in China. A high-performance liquid chromatography-diode array detector (HPLC-DAD) fingerprint method was developed to present the comprehensive phytochemical profile of the crude drug. Thirteen major compounds were separated and identified by HPLC coupled with time-of-flight mass spectrometry (HPLC/TOF-MS), namely psoralenoside (PO), isopsoralenoside (IPO), psoralen (PS), isopsoralen (IPS), neobavaisoflavone (NBF), bavachin (BC), corylin (CN), bavachromene (BCM), psoralidin (PD), isobavachalcone (IBC), bacachinin (BCN), corylifol A (CA) and bakuchiol (BK). Then quantitative analysis of multiple components by single marker (QAMS) was applied in content determination of PO, IPO, PS, IPS, BC, IBC, BCN, CA and BK, with NBF as the internal standard. The calculation results indicated no significant difference from the traditional external standard method (p > 0.05, RSD < 2.62%), suggesting that QAMS is a reliable and convenient method for content determination of multiple chemical compositions, especially when there is a shortage of reference substances. In conclusion, simultaneous qualitative and quantitative analysis of Psoraleae Fructus may be fulfilled through the newly proposed method of QAMS combined with HPLC-DAD/TOF-MS fingerprint. Copyright © 2017 John Wiley & Sons, Ltd.

  11. Efficacy of Fish Oil on Serum of TNFα, IL-1β, and IL-6 Oxidative Stress Markers in Multiple Sclerosis Treated with Interferon Beta-1b

    PubMed Central

    Ramirez-Ramirez, V.; Macias-Islas, M. A.; Ortiz, G. G.; Pacheco-Moises, F.; Torres-Sanchez, E. D.; Sorto-Gomez, T. E.; Cruz-Ramos, J. A.; Orozco-Aviña, G.; Celis de la Rosa, A. J.

    2013-01-01

    Multiple sclerosis (MS) is a chronic inflammatory disease, which leads to focal plaques of demyelination and tissue injury in the central nervous system. Oxidative stress is also thought to promote tissue damage in multiple sclerosis. Current research findings suggest that omega-3 polyunsaturated fatty acids (PUFAs) such as eicosapenta-enoic acid (EPA) and docosahexaenoic acid (DHA) contained in fish oil may have anti-inflammatory, antioxidant, and neuroprotective effects. The aim of the present work was to evaluate the efficacy of fish oil supplementation on serum proinflammatory cytokine levels, oxidative stress markers, and disease progression in MS. 50 patients with relapsing-remitting MS were enrolled. The experimental group received orally 4 g/day of fish oil for 12 months. The primary outcome was serum TNFα levels; secondary outcomes were IL-1β 1b, IL-6, nitric oxide catabolites, lipoperoxides, progression on the expanded disability status scale (EDSS), and annualized relapses rate (ARR). Fish oil treatment decreased the serum levels of TNFα, IL-1β, IL-6, and nitric oxide metabolites compared with placebo group (P ≤ 0.001). There was no significant difference in serum lipoperoxide levels during the study. No differences in EDSS and ARR were found. Conclusion. Fish oil supplementation is highly effective in reducing the levels of cytokines and nitric oxide catabolites in patients with relapsing-remitting MS. PMID:23861993

  12. Two versatile shuttle vectors for Thermus thermophilus-Escherichia coli containing multiple cloning sites, lacZα gene and kanamycin or hygromycin resistance marker.

    PubMed

    Fujita, Atsushi; Misumi, Yoshio; Koyama, Yoshinori

    2012-05-01

    Two versatile shuttle vectors for Thermus thermophilus and Escherichia coli were developed on the basis of the T. thermophilus cryptic plasmid pTT8 and E. coli vector pUC13. These shuttle vectors, pTRK1T and pTRH1T, carry a gene encoding a protein homologous to replication protein derived from pTT8, a replicon for E. coli, new multiple cloning sites and a lacZα gene from E. coli vector pUC13, and also have a gene encoding a thermostable protein that confers resistance to kanamycin or hygromycin, which can be used as a selection marker in T. thermophilus. These shuttle vectors are useful to develop enzymes and proteins of biotechnological interest. We also constructed a plasmid, pUC13T, which carries the same multiple cloning sites of pTRK1T and pTRH1T. These vectors should facilitate cloning procedures both in E. coli and T. thermophilus.

  13. Efficacy of fish oil on serum of TNF α , IL-1 β , and IL-6 oxidative stress markers in multiple sclerosis treated with interferon beta-1b.

    PubMed

    Ramirez-Ramirez, V; Macias-Islas, M A; Ortiz, G G; Pacheco-Moises, F; Torres-Sanchez, E D; Sorto-Gomez, T E; Cruz-Ramos, J A; Orozco-Aviña, G; Celis de la Rosa, A J

    2013-01-01

    Multiple sclerosis (MS) is a chronic inflammatory disease, which leads to focal plaques of demyelination and tissue injury in the central nervous system. Oxidative stress is also thought to promote tissue damage in multiple sclerosis. Current research findings suggest that omega-3 polyunsaturated fatty acids (PUFAs) such as eicosapenta-enoic acid (EPA) and docosahexaenoic acid (DHA) contained in fish oil may have anti-inflammatory, antioxidant, and neuroprotective effects. The aim of the present work was to evaluate the efficacy of fish oil supplementation on serum proinflammatory cytokine levels, oxidative stress markers, and disease progression in MS. 50 patients with relapsing-remitting MS were enrolled. The experimental group received orally 4 g/day of fish oil for 12 months. The primary outcome was serum TNF α levels; secondary outcomes were IL-1 β 1b, IL-6, nitric oxide catabolites, lipoperoxides, progression on the expanded disability status scale (EDSS), and annualized relapses rate (ARR). Fish oil treatment decreased the serum levels of TNF α , IL-1 β , IL-6, and nitric oxide metabolites compared with placebo group (P ≤ 0.001). There was no significant difference in serum lipoperoxide levels during the study. No differences in EDSS and ARR were found. Fish oil supplementation is highly effective in reducing the levels of cytokines and nitric oxide catabolites in patients with relapsing-remitting MS.

  14. Serum prealbumin: an independent marker of short-term energy intake in the presence of multiple-organ disease involvement.

    PubMed

    Caccialanza, Riccardo; Palladini, Giovanni; Klersy, Catherine; Cereda, Emanuele; Bonardi, Chiara; Quarleri, Lara; Vadacca, Giovanbattista; Albertini, Riccardo; Merlini, Giampaolo

    2013-03-01

    Serum prealbumin has a prognostic value in several diseases, but its serum levels can be influenced by different factors. However, a multivariable analysis to test the independent effect of each has not yet, to our knowledge, been performed. The aim of this cross-sectional study was to investigate the association between prealbumin and several factors possibly affecting its serum levels to test the potential of using prealbumin as an indicator of nutritional status and short-term energy intake in patients newly diagnosed with immunoglobulin light-chain amyloidosis. Multivariable general linear regression models of non-collinear variables were fitted to assess the association of demographic (sex, age), nutritional (short-term energy intake, unintentional weight loss, body mass index), and clinical (cardiac and liver involvement, kidney function, C-reactive protein) parameters with serum prealbumin levels in 187 patients newly diagnosed with immunoglobulin light-chain amyloidosis. Serum prealbumin levels were associated with C-reactive protein and short-term energy intake (P < 0.001 for both). A significant association was also detected with age (P = 0.023), serum creatinine (P = 0.017), liver involvement (P = 0.002), and peripheral edema (P = 0.032). In a prespecified subgroup analysis (n = 140) in patients with normal C-reactive protein level (<0.5 mg/dL), all other associations were confirmed. A significant relation was also observed with sex (P = 0.022) and body mass index (P = 0.041). Serum prealbumin is associated with short-term energy intake independently of the presence of multiple-organ involvement and inflammation. Its serum levels should be always interpreted in light of its influencing factors, among which inflammation and liver and kidney functions appear predominant. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. NFKB1 -94ins/delATTG polymorphism is a novel prognostic marker in first line-treated multiple myeloma.

    PubMed

    Varga, Gergely; Mikala, Gábor; Andrikovics, Hajnalka; Koszarska, Magdalena; Balassa, Katalin; Ádám, Emma; Kozma, András; Tordai, Attila; Masszi, Tamás

    2015-03-01

    Nuclear factor kappa B (NFKB) plays an important role in multiple myeloma (MM), and bortezomib affects this pathway. We retrospectively analysed the effect of the NFKB1 -94ins/delATTG polymorphism on the survival of 295 MM patients treated at a single centre. The median progression-free survival (PFS) was 790 (659-921) d in patients with NFKB1 homozygous insertion genotype (I/I, n = 99) and 624 (515-733) d in deletion-carriers (I/D&D/D, n = 196, P = 0·013). In multivariate analysis, I/I carriers showed a favourable PFS compared to I/D&D/D with a hazard ratio of 0·622 (0·457-0·847), P = 0·003, in addition to international staging system (ISS) score, fluorescence in situ hybridization (FISH) risk score, age and bortezomib treatment. I/I patients benefited more from bortezomib treatment [PFS 902 (703-1101) and 580 (343-817), P = 0·008] than I/D&D/D patients [PFS 659 (487-831) and 488 (323-653), P = 0·531]; in addition the beneficial effect of low ISS score was not observed in the I/D&D/D group [PFS 639 (454-824) and 650 (458-842), P = 0·226], while it was clear in I/I patients [PFS 1140 (803-1477) and 580 (408-752), P < 0·001]. We conclude that homozygous carriers of the insertion allele of the NFKB1 -94ins/delATTG polymorphism have a better prognosis and probably benefit more from bortezomib treatment than MM patients carrying the deletion allele.

  16. TGFbetaR2 aberrant methylation is a potential prognostic marker and therapeutic target in multiple myeloma.

    PubMed

    de Carvalho, Fabrício; Colleoni, Gisele W B; Almeida, Manuella S Sampaio; Carvalho, André L; Vettore, André L

    2009-10-15

    Multiple myeloma (MM) is an incurable hematological malignancy. Different studies demonstrated the occurrence of genetic and epigenetic alterations in MM. The aberrant methylation is one of the most frequent epigenetic alterations in human genome. This study evaluated the aberrant methylation status of 20 genes in 51 MM samples by quantitative methylation-specific PCR (QMSP) and compared the methylation profile with clinicopathological characteristics of the patients. The QMSP analyses showed that PTGS2 (100.0%), SFN (100.0%), CDKN2B (90.2%), CDH1 (88.2%), ESR1 (72.5%), HIC1 (70.5%), CCND2 (62.7%), DCC (45.1%) and TGFbetaR2 (39.2%) are frequently hypermethylated in MM while aberrant methylation of RARbeta (16.6%), MGMT (12.5%), AIM1 (12.5%), CDKN2A (8.3%), SOCS1 (8.3%), CCNA1 (8.3%) and THBS1 (4.1%) are rare events. There was no methylation of GSTP1, MINT31, p14ARF and RB1 in the samples tested. Hypermethylation of ESR1 was correlated positively with isotype IgA, while aberrant methylation of THBS1 correlated negatively with isotype IgG. Furthermore, hypermethylation of DCC and TGFbetaR2 were correlated with poor survival. The multivariate analysis showed ISS and TGFbetaR2 hypermethylation strongly correlated with poor outcome. This study represents the first quantitative evaluation of promoter methylation in MM and our data provide evidence that TGFbetaR2 hypermethylation, besides ISS, may be useful as prognostic indicator in this disease.

  17. Ultrasensitive non enzymatic multiple immunosensor for tumor markers detection by coupling DNA hybridization chain reaction with intercalated molecules.

    PubMed

    Guo, Jinjin; Wang, Junchun; Zhang, Junjun; Zhang, Wenjuan; Zhang, Yuzhong

    2017-04-15

    In this study, we tried coupling the small signal molecules that could intercalate into DNA double helix with hybridization chain reaction (HCR) technique to fabricate a multiple immunosensor. Doxorubicin hydrochloride (DXH) and methylene blue (MB) were used as signal molecules and alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) were selected as model biomarkers. The immunosensor mainly consists of three parts as follows: First, two different primary antibodies (Ab1) immobilized on the surface of gold nanoparticles (Au NPs); Second, secondary antibodies (Ab2) conjugated with DNA primer; Third, long DNA concatemers from HCR were used as a carrier to intercalate amounts of signal molecules (DXH or MB). A sandwich immunocomplex was formed among primary antibodies, target biomarkers and secondary antibodies conjugated with DNA primer via specific recognition reaction. Afterwards, DNA concatemers intercalating amounts of DXH or MB were linked to DNA primer via DNA hybridization. Square wave voltammetry (SWV) was employed to record the response signals from electroactive molecules DXH and MB, and two distinguishable signals were obtained, which peak potentials were at about -0.30V (corresponding to MB) and -0.70V (corresponding to DXH, both vs SCE), respectively. The signal intensities of MB and DXH were linearly related to the logarithm of biomarkers concentration in the range of 0.05pgmL(-1)-25ngmL(-1), and the limit of detection were 0.03pgmL(-1) for CEA and 0.02pgmL(-1) for AFP (at S/N=3), respectively. Furthermore, the immunosensor exhibited a sensitive electrochemical response to biomarkers in human serum samples and the results obtained were in accordance with reference method, indicating the immunosensor can be applied to real sample analysis in clinic diagnosis.

  18. Identification of Gene Markers Associated with Aggressive Meningioma by Filtering across Multiple Sets of Gene Expression Arrays

    PubMed Central

    Stuart, Jourdan E.; Lusis, Eriks A.; Scheck, Adrienne C.; Coons, Stephen W.; Lal, Anita; Perry, Arie; Gutmann, David H.

    2013-01-01

    Meningiomasare common intracranial tumors but relatively little is known about the genetic events responsible for their clinical diversity. While recent genomic studies have provided clues, the genes identified often differ among publications. We used microarray expression profiling to identify genes that are differentially expressed, with at least a 4-fold change, between grade I and grade III meningiomas. We filtered this initial set of potential biomarkers through a second cohort of meningiomas and then verified the remaining genes by quantitative polymerase chain reaction followed by examination using a third microarray expression cohort. Using this approach, we identified 9 overexpressed (TPX2, RRM2, TOP2A, PI3, BIRC5, CDC2, NUSAP1, DLG7, SOX11) and 2 underexpressed (TIMP3, KCNMA1) genes in grade III vs. grade I meningiomas. As a further validation step, we analyzed these genes in a fourth cohort and found that patients with grade II meningiomas with high topoisomerase 2-α protein expression (greater than 5% labeling-index) had shorter times to death than patients with low expression. We believe that this multistep, multi-cohort approach provides a robust method for reducing false positives while generating a list of reproducible candidate genes that are associated with clinically aggressive meningioma and are suitable for analysis for their potential prognostic value. PMID:21157382

  19. Welder analyzer

    NASA Technical Reports Server (NTRS)

    Miller, L. L.

    1968-01-01

    Welder analyzer circuit evaluates and certifies resistance welding machines. The analyzer measures peak current, peak voltage, peak power, total energy, and first-pulse energy. It is used as an energy monitor while welding is being performed, or a precision shunt load for a pure electrical evaluation of the weld machine.

  20. Genome-Wide Analysis of Simple Sequence Repeats and Efficient Development of Polymorphic SSR Markers Based on Whole Genome Re-Sequencing of Multiple Isolates of the Wheat Stripe Rust Fungus

    PubMed Central

    Luo, Huaiyong; Wang, Xiaojie; Zhan, Gangming; Wei, Guorong; Zhou, Xinli; Zhao, Jing; Huang, Lili; Kang, Zhensheng

    2015-01-01

    The biotrophic parasitic fungus Puccinia striiformis f. sp. tritici (Pst) causes stripe rust, a devastating disease of wheat, endangering global food security. Because the Pst population is highly dynamic, it is difficult to develop wheat cultivars with durable and highly effective resistance. Simple sequence repeats (SSRs) are widely used as molecular markers in genetic studies to determine population structure in many organisms. However, only a small number of SSR markers have been developed for Pst. In this study, a total of 4,792 SSR loci were identified using the whole genome sequences of six isolates from different regions of the world, with a marker density of one SSR per 22.95 kb. The majority of the SSRs were di- and tri-nucleotide repeats. A database containing 1,113 SSR markers were established. Through in silico comparison, the previously reported SSR markers were found mainly in exons, whereas the SSR markers in the database were mostly in intergenic regions. Furthermore, 105 polymorphic SSR markers were confirmed in silico by their identical positions and nucleotide variations with INDELs identified among the six isolates. When 104 in silico polymorphic SSR markers were used to genotype 21 Pst isolates, 84 produced the target bands, and 82 of them were polymorphic and revealed the genetic relationships among the isolates. The results show that whole genome re-sequencing of multiple isolates provides an ideal resource for developing SSR markers, and the newly developed SSR markers are useful for genetic and population studies of the wheat stripe rust fungus. PMID:26068192

  1. Analyzing multiple endpoints in clinical trials of pain treatments: IMMPACT recommendations. Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials.

    PubMed

    Turk, Dennis C; Dworkin, Robert H; McDermott, Michael P; Bellamy, Nicholas; Burke, Laurie B; Chandler, Julie M; Cleeland, Charles S; Cowan, Penney; Dimitrova, Rozalina; Farrar, John T; Hertz, Sharon; Heyse, Joseph F; Iyengar, Smriti; Jadad, Alejandro R; Jay, Gary W; Jermano, John A; Katz, Nathaniel P; Manning, Donald C; Martin, Susan; Max, Mitchell B; McGrath, Patrick; McQuay, Henry J; Quessy, Steve; Rappaport, Bob A; Revicki, Dennis A; Rothman, Margaret; Stauffer, Joseph W; Svensson, Ola; White, Richard E; Witter, James

    2008-10-31

    The increasing complexity of randomized clinical trials and the practice of obtaining a wide variety of measurements from study participants have made the consideration of multiple endpoints a critically important issue in the design, analysis, and interpretation of clinical trials. Failure to consider important outcomes can limit the validity and utility of clinical trials; specifying multiple endpoints for the evaluation of treatment efficacy, however, can increase the rate of false positive conclusions about the efficacy of a treatment. We describe the use of multiple endpoints in the design, analysis, and interpretation of pain clinical trials, and review available strategies and methods for addressing multiplicity. To decrease the probability of a Type I error (i.e., the likelihood of obtaining statistically significant results by chance) in pain clinical trials, the use of gatekeeping procedures and other methods that correct for multiple analyses is recommended when a single primary endpoint does not adequately reflect the overall benefits of treatment. We emphasize the importance of specifying in advance the outcomes and clinical decision rule that will serve as the basis for determining that a treatment is efficacious and the methods that will be used to control the overall Type I error rate.

  2. Changes and variability of proton density and T1 relaxation times in early multiple sclerosis: MRI markers of neuronal damage in the cerebral cortex.

    PubMed

    Gracien, René-Maxime; Reitz, Sarah C; Hof, Stephanie Michelle; Fleischer, Vinzenz; Zimmermann, Hilga; Droby, Amgad; Steinmetz, Helmuth; Zipp, Frauke; Deichmann, Ralf; Klein, Johannes C

    2016-08-01

    Proton density (PD) and T1 relaxation time are promising quantitative MRI (qMRI) markers of neuronal damage in multiple sclerosis (MS). However, it is unknown whether cortical differences of these parameters between patients and controls exist in the early stages of disease. This study investigates cortical T1 and PD in early MS stages, hypothesizing that these are altered and display a high spatial variability. Quantitative T1 and PD mapping was performed on 11 patients with clinically isolated syndrome (CIS)/early MS in remission and 11 healthy controls. The normal appearing cortical gray matter was extracted, lobar regions were identified, and mean values and standard deviations of both parameters were calculated within each region. Increased PD was detected in MS/CIS patients in the cerebral cortex as a whole and all subregions, indicating an increase of water content. Increase of PD variability reached significance in the whole cortex and in the frontal and parietal regions. Longer T1 relaxation times and increased variability were found in the cerebral cortex in all regions studied, indicating a change of microstructural tissue composition that is spatially heterogeneous. The data show spatially heterogeneous cortical involvement in early MS is reflected in T1 and PD qMRI. • Cortical involvement in early MS is reflected in T1/PD quantitative MRI. • The changes are spatially heterogeneous. • Cortical damage goes beyond increased water content.

  3. High Interferon-γ Uniquely in Vδ1 T Cells Correlates with Markers of Inflammation and Axonal Damage in Early Multiple Sclerosis

    PubMed Central

    Singh, Avadhesh Kumar; Novakova, Lenka; Axelsson, Markus; Malmeström, Clas; Zetterberg, Henrik; Lycke, Jan; Cardell, Susanna L.

    2017-01-01

    We have identified a population of T lymphocytes in peripheral blood, Vδ1 TCRγδ T lymphocytes, which unexpectedly was uniquely expressing high production of interferon-γ in newly diagnosed, untreated multiple sclerosis (MS) patients. IFN-γ production in this population distinctly correlated to parameters of clinical disease activity, inflammation, and neuronal damage. These Vδ1 T lymphocytes belong to a population of innate T lymphocytes that recognize antigen in the context of CD1d/CD1c and which include reactivity to the myelin glycosphingolipid sulfatide. Importantly, patients treated with natalizumab, blocking leukocyte transmigration to central nervous system, had completely normalized levels of interferon-γ-producing Vδ1 T lymphocytes. A biomarker and early sign of demyelinating disease in MS is much warranted and would help identify immunopathogenesis and prognosis of disease as well as monitor success with adequate treatment. The present study identifies the Vδ1 T lymphocytes as an early marker of MS and a possible link to understanding the disease etiology. PMID:28337205

  4. Multiple markers pyrosequencing reveals highly diverse and host-specific fungal communities on the mangrove trees Avicennia marina and Rhizophora stylosa.

    PubMed

    Arfi, Yonathan; Buée, Marc; Marchand, Cyril; Levasseur, Anthony; Record, Eric

    2012-02-01

    Fungi are important actors in ecological processes and trophic webs in mangroves. Although saprophytic fungi occurring in the intertidal part of mangrove have been well studied, little is known about the diversity and structure of the fungal communities in this ecosystem or about the importance of functional groups like pathogens and mutualists. Using tag-encoded 454 pyrosequencing of the ITS1, ITS2, nu-ssu-V5 and nu-ssu-V7 regions, we studied and compared the fungal communities found on the marine and aerial parts of Avicennia marina and Rhizophora stylosa trees in a mangrove in New Caledonia. A total of 209,544 reads were analysed, corresponding to several thousand molecular operational taxonomic units (OTU). There is a marked zonation in the species distribution, with most of the OTU being found specifically in one of the microhabitat studied. Ascomycetes are the dominant phylum (82%), Basidiomycetes are very rare (3%), and 15% of the sequences correspond to unknown taxa. Our results indicate that host specificity is a key factor in the distribution of the highly diverse fungal communities, in both the aerial and intertidal parts of the trees. This study also validates the usefulness of multiple markers in tag-encoded pyrosequencing to consolidate and refine the assessment of the taxonomic diversity.

  5. High Interferon-γ Uniquely in Vδ1 T Cells Correlates with Markers of Inflammation and Axonal Damage in Early Multiple Sclerosis.

    PubMed

    Singh, Avadhesh Kumar; Novakova, Lenka; Axelsson, Markus; Malmeström, Clas; Zetterberg, Henrik; Lycke, Jan; Cardell, Susanna L

    2017-01-01

    We have identified a population of T lymphocytes in peripheral blood, Vδ1 TCRγδ T lymphocytes, which unexpectedly was uniquely expressing high production of interferon-γ in newly diagnosed, untreated multiple sclerosis (MS) patients. IFN-γ production in this population distinctly correlated to parameters of clinical disease activity, inflammation, and neuronal damage. These Vδ1 T lymphocytes belong to a population of innate T lymphocytes that recognize antigen in the context of CD1d/CD1c and which include reactivity to the myelin glycosphingolipid sulfatide. Importantly, patients treated with natalizumab, blocking leukocyte transmigration to central nervous system, had completely normalized levels of interferon-γ-producing Vδ1 T lymphocytes. A biomarker and early sign of demyelinating disease in MS is much warranted and would help identify immunopathogenesis and prognosis of disease as well as monitor success with adequate treatment. The present study identifies the Vδ1 T lymphocytes as an early marker of MS and a possible link to understanding the disease etiology.

  6. Bortezomib resistance can be reversed by induced expression of plasma cell maturation markers in a mouse in vitro model of multiple myeloma.

    PubMed

    Stessman, Holly A F; Mansoor, Aatif; Zhan, Fenghuang; Linden, Michael A; Van Ness, Brian; Baughn, Linda B

    2013-01-01

    Multiple myeloma (MM), the second most common hematopoietic malignancy, remains an incurable plasma cell (PC) neoplasm. While the proteasome inhibitor, bortezomib (Bz) has increased patient survival, resistance represents a major treatment obstacle as most patients ultimately relapse becoming refractory to additional Bz therapy. Current tests fail to detect emerging resistance; by the time patients acquire resistance, their prognosis is often poor. To establish immunophenotypic signatures that predict Bz sensitivity, we utilized Bz-sensitive and -resistant cell lines derived from tumors of the Bcl-X(L)/Myc mouse model of PC malignancy. We identified significantly reduced expression of two markers (CD93, CD69) in "acquired" (Bz-selected) resistant cells. Using this phenotypic signature, we isolated a subpopulation of cells from a drug-naïve, Bz-sensitive culture that displayed "innate" resistance to Bz. Although these genes were identified as biomarkers, they may indicate a mechanism for Bz-resistance through the loss of PC maturation which may be induced and/or selected by Bz. Significantly, induction of PC maturation in both "acquired" and "innate" resistant cells restored Bz sensitivity suggesting a novel therapeutic approach for reversing Bz resistance in refractory MM.

  7. Process Analyzer

    NASA Technical Reports Server (NTRS)

    1994-01-01

    The ChemScan UV-6100 is a spectrometry system originally developed by Biotronics Technologies, Inc. under a Small Business Innovation Research (SBIR) contract. It is marketed to the water and wastewater treatment industries, replacing "grab sampling" with on-line data collection. It analyzes the light absorbance characteristics of a water sample, simultaneously detects hundreds of individual wavelengths absorbed by chemical substances in a process solution, and quantifies the information. Spectral data is then processed by ChemScan analyzer and compared with calibration files in the system's memory in order to calculate concentrations of chemical substances that cause UV light absorbance in specific patterns. Monitored substances can be analyzed for quality and quantity. Applications include detection of a variety of substances, and the information provided enables an operator to control a process more efficiently.

  8. Blood Analyzer

    NASA Technical Reports Server (NTRS)

    1992-01-01

    In the 1970's, NASA provided funding for development of an automatic blood analyzer for Skylab at the Oak Ridge National Laboratory (ORNL). ORNL devised "dynamic loading," which employed a spinning rotor to load, transfer, and analyze blood samples by centrifugal processing. A refined, commercial version of the system was produced by ABAXIS and is marketed as portable ABAXIS MiniLab MCA. Used in a doctor's office, the equipment can perform 80 to 100 chemical blood tests on a single drop of blood and report results in five minutes. Further development is anticipated.

  9. Defibrillator analyzers.

    PubMed

    1999-12-01

    Defibrillator analyzers automate the inspection and preventive maintenance (IPM) testing of defibrillators. They need to be able to test at least four basic defibrillator performance characteristics: discharge energy, synchronized-mode operation, automated external defibrillation, and ECG monitoring. We prefer that they also be able to test a defibrillator's external noninvasive pacing function--but this is not essential if a facility already has a pacemaker analyzer that can perform this testing. In this Evaluation, we tested seven defibrillator analyzers from six suppliers. All seven units accurately measure the energies of a variety of discharge wave-forms over a wide range of energy levels--from 1 J for use in a neonatal intensive care unit to 360 J for use on adult patients requiring maximum discharge energy. Most of the analyzers are easy to use. However, only three of the evaluated units could perform the full range of defibrillator tests that we prefer. We rated these units Acceptable--Preferred. Three more units could perform four of the five tests, they could not test the pacing feature of a defibrillator. These units were rated Acceptable. The seventh unit could perform only discharge energy testing and synchronized-mode testing and was difficult to use. We rate that unit Acceptable--Not Recommended.

  10. Marker development

    SciTech Connect

    Adams, M.R.

    1987-05-01

    This report is to discuss the marker development for radioactive waste disposal sites. The markers must be designed to last 10,000 years, and place no undue burdens on the future generations. Barriers cannot be constructed that preclude human intrusion. Design specifications for surface markers will be discussed, also marker pictograms will also be covered.

  11. Process Analyzer

    NASA Technical Reports Server (NTRS)

    1993-01-01

    Under a NASA Small Business Innovation Research (SBIR) contract, Axiomatics Corporation developed a shunting Dielectric Sensor to determine the nutrient level and analyze plant nutrient solutions in the CELSS, NASA's space life support program. (CELSS is an experimental facility investigating closed-cycle plant growth and food processing for long duration manned missions.) The DiComp system incorporates a shunt electrode and is especially sensitive to changes in dielectric property changes in materials at measurements much lower than conventional sensors. The analyzer has exceptional capabilities for predicting composition of liquid streams or reactions. It measures concentrations and solids content up to 100 percent in applications like agricultural products, petrochemicals, food and beverages. The sensor is easily installed; maintenance is low, and it can be calibrated on line. The software automates data collection and analysis.

  12. Oxygen analyzer

    DOEpatents

    Benner, William H.

    1986-01-01

    An oxygen analyzer which identifies and classifies microgram quantities of oxygen in ambient particulate matter and for quantitating organic oxygen in solvent extracts of ambient particulate matter. A sample is pyrolyzed in oxygen-free nitrogen gas (N.sub.2), and the resulting oxygen quantitatively converted to carbon monoxide (CO) by contact with hot granular carbon (C). Two analysis modes are made possible: (1) rapid determination of total pyrolyzable oxygen obtained by decomposing the sample at 1135.degree. C., or (2) temperature-programmed oxygen thermal analysis obtained by heating the sample from room temperature to 1135.degree. C. as a function of time. The analyzer basically comprises a pyrolysis tube containing a bed of granular carbon under N.sub.2, ovens used to heat the carbon and/or decompose the sample, and a non-dispersive infrared CO detector coupled to a mini-computer to quantitate oxygen in the decomposition products and control oven heating.

  13. Oxygen analyzer

    DOEpatents

    Benner, W.H.

    1984-05-08

    An oxygen analyzer which identifies and classifies microgram quantities of oxygen in ambient particulate matter and for quantitating organic oxygen in solvent extracts of ambient particulate matter. A sample is pyrolyzed in oxygen-free nitrogen gas (N/sub 2/), and the resulting oxygen quantitatively converted to carbon monoxide (CO) by contact with hot granular carbon (C). Two analysis modes are made possible: (1) rapid determination of total pyrolyzable obtained by decomposing the sample at 1135/sup 0/C, or (2) temperature-programmed oxygen thermal analysis obtained by heating the sample from room temperature to 1135/sup 0/C as a function of time. The analyzer basically comprises a pyrolysis tube containing a bed of granular carbon under N/sub 2/, ovens used to heat the carbon and/or decompose the sample, and a non-dispersive infrared CO detector coupled to a mini-computer to quantitate oxygen in the decomposition products and control oven heating.

  14. MULTICHANNEL ANALYZER

    DOEpatents

    Kelley, G.G.

    1959-11-10

    A multichannel pulse analyzer having several window amplifiers, each amplifier serving one group of channels, with a single fast pulse-lengthener and a single novel interrogation circuit serving all channels is described. A pulse followed too closely timewise by another pulse is disregarded by the interrogation circuit to prevent errors due to pulse pileup. The window amplifiers are connected to the pulse lengthener output, rather than the linear amplifier output, so need not have the fast response characteristic formerly required.

  15. Contamination Analyzer

    NASA Technical Reports Server (NTRS)

    1994-01-01

    Measurement of the total organic carbon content in water is important in assessing contamination levels in high purity water for power generation, pharmaceutical production and electronics manufacture. Even trace levels of organic compounds can cause defects in manufactured products. The Sievers Model 800 Total Organic Carbon (TOC) Analyzer, based on technology developed for the Space Station, uses a strong chemical oxidizing agent and ultraviolet light to convert organic compounds in water to carbon dioxide. After ionizing the carbon dioxide, the amount of ions is determined by measuring the conductivity of the deionized water. The new technique is highly sensitive, does not require compressed gas, and maintenance is minimal.

  16. CCFP Analyzer

    NASA Image and Video Library

    2016-05-06

    ISS047e106715 (05/06/2016) --- ESA (European Space Agency astronaut Tim Peake unpacks a cerebral and cochlear fluid pressure (CCFP) analyzer. The device is being tested to measure the pressure of the fluid in the skull, also known as intracranial pressure, which may increase due to fluid shifts in the body while in microgravity. It is hypothesized that the headward fluid shift that occurs during space flight leads to increased pressure in the brain, which may push on the back of the eye, causing it to change shape.

  17. Gas Analyzer

    NASA Technical Reports Server (NTRS)

    1983-01-01

    A miniature gas chromatograph, a system which separates a gaseous mixture into its components and measures the concentration of the individual gases, was designed for the Viking Lander. The technology was further developed under National Institute for Occupational Safety and Health (NIOSH) and funded by Ames Research Center/Stanford as a toxic gas leak detection device. Three researchers on the project later formed Microsensor Technology, Inc. to commercialize the product. It is a battery-powered system consisting of a sensing wand connected to a computerized analyzer. Marketed as the Michromonitor 500, it has a wide range of applications.

  18. An efficient and reproducible method for in vitro clonal multiplication of Rauvolfia tetraphylla L. and evaluation of genetic stability using DNA-based markers.

    PubMed

    Faisal, Mohammad; Alatar, Abdulrahman A; Ahmad, Naseem; Anis, Mohammad; Hegazy, Ahmad K

    2012-12-01

    An efficient protocol is described for the rapid in vitro clonal propagation of an endangered medicinal plant, Rauvolfia tetraphylla L., through high frequency shoot induction from nodal explants collected from young shoots of a field grown plant. Effects of growth regulators [6-benzyladenine (BA), kinetin (Kin) 2iP, or α-naphthalene acetic acid (NAA)], carbohydrates, different medium [Murashige and Skoog (MS), Woody Plant Medium (WPM), Gamborg medium (B5), Linsmier and Skoog medium (LS)], and various pH levels on in vitro morphogenesis were investigated. The highest frequency of shoot regeneration (90 %) and maximum number of shoot (35.4 ± 2.3) per explant were observed on WPM medium supplemented with 7.5 μM BA, 2.5 μM NAA, and 30 g/l sucrose at pH 5.8. Well-developed shoots, 4-5 cm in length, were successfully rooted ex vitro at 90 % by a 30-min pulse treatment with 150 μM IBA prior to their transfer in planting substrates. The survival rate of transplantation reached 90 % when transferred to field condition. Genetic stability of micropropagated plantlets was assessed and compared with mother plant using Random Amplified Polymorphic DNA and Inter Simple Sequence Repeats markers. No variation was observed in DNA fingerprinting patterns among the micropropagated plants, which were similar to that of the donor plant illustrating their genetic uniformity and clonal fidelity. This confirms that clonal propagation of this plant using axillary shoot buds can be used for commercial exploitation of the selected genotype where a high degree of fidelity is an essential prerequisite. The work contributed to a better in vitro regeneration and clonal mass multiplication of R. tetraphylla and to develop a strategy for the germplasm conservation of this endangered medicinal plant.

  19. Effect of vegetable and carotenoid consumption on aberrant crypt multiplicity, a surrogate end-point marker for colorectal cancer in azoxymethane-induced rats.

    PubMed

    Rijken, P J; Timmer, W G; van de Kooij, A J; van Benschop, I M; Wiseman, S A; Meijers, M; Tijburg, L B

    1999-12-01

    Epidemiological studies indicate that increased vegetable consumption reduces the risk of colorectal cancer mortality. In the present study we have investigated the effect of consumption of standard diets supplemented with freeze-dried vegetables (peas, spinach, sprouts and broccoli) and carotenoids (all-trans beta-carotene and palm oil carotenoid extract) on surrogate end-point markers for colorectal cancer in an azoxymethane-induced rat model. Mean aberrant crypt multiplicity was reduced (19%) by the pea-supplemented diet only (P < 0.05). The vegetable-induced effect was more apparent in aberrant crypt foci with higher multiplicity. Intervention with diets supplemented with peas, spinach, sprouts and a mix of all vegetables reduced the number of foci with >2 aberrant crypts/focus by 37, 26, 23 and 26%, respectively (P < 0.05). Even more pronounced effects were observed in foci with >3 aberrant crypts/focus, with reductions of approximately 50% in the pea and spinach intervention groups. All-trans beta-carotene and palm oil-derived carotenoids, supplied at similar doses to those expected in the vegetable diets, inhibited ACM only marginally. Aberrant crypt foci formation in groups fed a sprout-supplemented diet prior to or following azoxymethane treatment was similar, indicating that this effect is due to inhibition of promotion rather than initiation of colorectal carcinogenesis. Vegetable and carotenoid consumption did not affect in situ proliferation of colonic crypt cells, as assessed by semi-automated image analysis of bromodeoxyuridine (BrdU)-positive nuclei. BrdU-negative nuclei of colonic crypt cells were reduced slightly in the combined vegetable groups, as compared with the control (P < 0.05). These data: (i) are in line with epidemiological evidence regarding beneficial effects of vegetable consumption on colorectal carcinogenesis; (ii) indicate that consumption of several types of vegetables inhibits early post-initiation events in colorectal

  20. Analyzing Orientations

    NASA Astrophysics Data System (ADS)

    Ruggles, Clive L. N.

    Archaeoastronomical field survey typically involves the measurement of structural orientations (i.e., orientations along and between built structures) in relation to the visible landscape and particularly the surrounding horizon. This chapter focuses on the process of analyzing the astronomical potential of oriented structures, whether in the field or as a desktop appraisal, with the aim of establishing the archaeoastronomical "facts". It does not address questions of data selection (see instead Chap. 25, "Best Practice for Evaluating the Astronomical Significance of Archaeological Sites", 10.1007/978-1-4614-6141-8_25) or interpretation (see Chap. 24, "Nature and Analysis of Material Evidence Relevant to Archaeoastronomy", 10.1007/978-1-4614-6141-8_22). The main necessity is to determine the azimuth, horizon altitude, and declination in the direction "indicated" by any structural orientation. Normally, there are a range of possibilities, reflecting the various errors and uncertainties in estimating the intended (or, at least, the constructed) orientation, and in more formal approaches an attempt is made to assign a probability distribution extending over a spread of declinations. These probability distributions can then be cumulated in order to visualize and analyze the combined data from several orientations, so as to identify any consistent astronomical associations that can then be correlated with the declinations of particular astronomical objects or phenomena at any era in the past. The whole process raises various procedural and methodological issues and does not proceed in isolation from the consideration of corroborative data, which is essential in order to develop viable cultural interpretations.

  1. 2-Acylamino- and 2,4-bis(acylamino)pyrimidines as supramolecular synthons analyzed by multiple noncovalent interactions. DFT, X-ray diffraction, and NMR spectral studies.

    PubMed

    Ośmiałowski, Borys; Kolehmainen, Erkki; Ikonen, Satu; Valkonen, Arto; Kwiatkowski, Adam; Grela, Izabela; Haapaniemi, Esa

    2012-11-02

    Intermolecular interactions of ten 2-acylamino and 2,4-bis(acylamino)pyrimidines (7 of which are previously unknown) have been investigated by X-ray structural, quantum chemical (DFT), and NMR spectral methods. Especially the concentration dependencies of the (1)H NMR chemical shifts and titrations with other molecules capable of multiple hydrogen bonding provided useful information regarding their association via triple or quadruple hydrogen bonding, which is controlled by the conformational preferences of 2-acylamino- and 2,4-bis(acylamino)pyrimidines. On comparison of the properties of 2-acylamino- and 2,4-bis(acylamino)pyrimidines with the corresponding pyridines, an additional nitrogen in the heterocyclic ring is the crucial factor in explaining the stability of various conformers and dimers of pyrimidines. Computational modeling of their dimerization (self-association) and heteroassociation supports the experimental findings. The substituent effects in 2-acylamino- and 2,4-bis(acylamino)pyrimidines are discussed via inter- and intramolecular terms. The subtle balance between several structural factors and their influence on the aggregation of studied pyrimidines was confirmed also by variable-temperature NMR and NOE experiments. X-ray structures of 2-methyl- and 2-adamantyl-CONH-pyrimidines revealed very different intermolecular interactions, showing the importance of the substituent size on the self-assembly process. As a whole NMR spectral, X-ray structural, and computational data of 2-acylamino- and 2,4-bis(acylamino)pyrimidines can be interpreted in terms of multiple intra-/intermolecular interactions.

  2. Speech analyzer

    NASA Technical Reports Server (NTRS)

    Lokerson, D. C. (Inventor)

    1977-01-01

    A speech signal is analyzed by applying the signal to formant filters which derive first, second and third signals respectively representing the frequency of the speech waveform in the first, second and third formants. A first pulse train having approximately a pulse rate representing the average frequency of the first formant is derived; second and third pulse trains having pulse rates respectively representing zero crossings of the second and third formants are derived. The first formant pulse train is derived by establishing N signal level bands, where N is an integer at least equal to two. Adjacent ones of the signal bands have common boundaries, each of which is a predetermined percentage of the peak level of a complete cycle of the speech waveform.

  3. Optical analyzer

    DOEpatents

    Hansen, A.D.

    1987-09-28

    An optical analyzer wherein a sample of particulate matter, and particularly of organic matter, which has been collected on a quartz fiber filter is placed in a combustion tube, and light from a light source is passed through the sample. The temperature of the sample is raised at a controlled rate and in a controlled atmosphere. The magnitude of the transmission of light through the sample is detected as the temperature is raised. A data processor, differentiator and a two pen recorder provide a chart of the optical transmission versus temperature and the rate of change of optical transmission versus temperature signatures (T and D) of the sample. These signatures provide information as to physical and chemical processes and a variety of quantitative and qualitative information about the sample. Additional information is obtained by repeating the run in different atmospheres and/or different rates or heating with other samples of the same particulate material collected on other filters. 7 figs.

  4. The severity of Minamata disease declined in 25 years: temporal profile of the neurological findings analyzed by multiple logistic regression model.

    PubMed

    Uchino, Makoto; Hirano, Teruyuki; Satoh, Hiroshi; Arimura, Kimiyoshi; Nakagawa, Masanori; Wakamiya, Jyunji

    2005-01-01

    Minamata disease (MD) was caused by ingestion of seafood from the methylmercury-contaminated areas. Although 50 years have passed since the discovery of MD, there have been only a few studies on the temporal profile of neurological findings in certified MD patients. Thus, we evaluated changes in neurological symptoms and signs of MD using discriminants by multiple logistic regression analysis. The severity of predictive index declined in 25 years in most of the patients. Only a few patients showed aggravation of neurological findings, which was due to complications such as spino-cerebellar degeneration. Patients with chronic MD aged over 45 years had several concomitant diseases so that their clinical pictures were complicated. It was difficult to differentiate chronic MD using statistically established discriminants based on sensory disturbance alone. In conclusion, the severity of MD declined in 25 years along with the modification by age-related concomitant disorders.

  5. Optical analyzer

    DOEpatents

    Hansen, Anthony D.

    1989-01-01

    An optical analyzer (10) wherein a sample (19) of particulate matter, and particularly of organic matter, which has been collected on a quartz fiber filter (20) is placed in a combustion tube (11), and light from a light source (14) is passed through the sample (19). The temperature of the sample (19) is raised at a controlled rate and in a controlled atmosphere. The magnitude of the transmission of light through the sample (19) is detected (18) as the temperature is raised. A data processor (23), differentiator (28) and a two pen recorder (24) provide a chart of the optical transmission versus temperature and the rate of change of optical transmission versus temperature signatures (T and D) of the sample (19). These signatures provide information as to physical and chemical processes and a variety of quantitative and qualitative information about the sample (19). Additional information is obtained by repeating the run in different atmospheres and/or different rates of heating with other samples of the same particulate material collected on other filters.

  6. Optical analyzer

    DOEpatents

    Hansen, Anthony D.

    1989-02-07

    An optical analyzer (10) wherein a sample (19) of particulate matter, and particularly of organic matter, which has been collected on a quartz fiber filter (20) is placed in a combustion tube (11), and light from a light source (14) is passed through the sample (19). The temperature of the sample (19) is raised at a controlled rate and in a controlled atmosphere. The magnitude of the transmission of light through the sample (19) is detected (18) as the temperature is raised. A data processor (23), differentiator (28) and a two pen recorder (24) provide a chart of the optical transmission versus temperature and the rate of change of optical transmission versus temperature signatures (T and D) of the sample (19). These signatures provide information as to physical and chemical processes and a variety of quantitative and qualitative information about the sample (19). Additional information is obtained by repeating the run in different atmospheres and/or different rates of heating with other samples of the same particulate material collected on other filters.

  7. ABSORPTION ANALYZER

    DOEpatents

    Brooksbank, W.A. Jr.; Leddicotte, G.W.; Strain, J.E.; Hendon, H.H. Jr.

    1961-11-14

    A means was developed for continuously computing and indicating the isotopic assay of a process solution and for automatically controlling the process output of isotope separation equipment to provide a continuous output of the desired isotopic ratio. A counter tube is surrounded with a sample to be analyzed so that the tube is exactly in the center of the sample. A source of fast neutrons is provided and is spaced from the sample. The neutrons from the source are thermalized by causing them to pass through a neutron moderator, and the neutrons are allowed to diffuse radially through the sample to actuate the counter. A reference counter in a known sample of pure solvent is also actuated by the thermal neutrons from the neutron source. The number of neutrons which actuate the detectors is a function of a concentration of the elements in solution and their neutron absorption cross sections. The pulses produced by the detectors responsive to each neu tron passing therethrough are amplified and counted. The respective times required to accumulate a selected number of counts are measured by associated timing devices. The concentration of a particular element in solution may be determined by utilizing the following relation: T2/Ti = BCR, where B is a constant proportional to the absorption cross sections, T2 is the time of count collection for the unknown solution, Ti is the time of count collection for the pure solvent, R is the isotopic ratlo, and C is the molar concentration of the element to be determined. Knowing the slope constant B for any element and when the chemical concentration is known, the isotopic concentration may be readily determined, and conversely when the isotopic ratio is known, the chemical concentrations may be determined. (AEC)

  8. Marker chromosomes.

    PubMed

    Rao, Kiran Prabhaker; Belogolovkin, Victoria

    2013-04-01

    Marker chromosomes are a morphologically heterogeneous group of structurally abnormal chromosomes that pose a significant challenge in prenatal diagnosis. Phenotypes associated with marker chromosomes are highly variable and range from normal to severely abnormal. Clinical outcomes are very difficult to predict when marker chromosomes are detected prenatally. In this review, we outline the classification, etiology, cytogenetic characterization, and clinical consequences of marker chromosomes, as well as practical approaches to prenatal diagnosis and genetic counseling.

  9. Elevations of inflammatory markers PTX3 and sST2 after resuscitation from cardiac arrest are associated with multiple organ dysfunction syndrome and early death.

    PubMed

    Ristagno, Giuseppe; Varpula, Tero; Masson, Serge; Greco, Marta; Bottazzi, Barbara; Milani, Valentina; Aleksova, Aneta; Sinagra, Gianfranco; Assandri, Roberto; Tiainen, Marjaana; Vaahersalo, Jukka; Kurola, Jouni; Barlera, Simona; Montanelli, Alessandro; Latini, Roberto; Pettilä, Ville; Bendel, Stepani; Skrifvars, Markus B

    2015-10-01

    A systemic inflammatory response is observed after cardiopulmonary resuscitation. We investigated two novel inflammatory markers, pentraxin 3 (PTX3) and soluble suppression of tumorigenicity 2 (sST2), in comparison with the classic high-sensitivity C-reactive protein (hsCRP), for prediction of early multiple organ dysfunction syndrome (MODS), early death, and long-term outcome after out-of-hospital cardiac arrest. PTX3, sST2, and hsCRP were assayed at ICU admission and 48 h later in 278 patients. MODS was defined as the 24 h non-neurological Sequential Organ Failure Assessment (SOFA) score ≥ 12. Intensive care unit (ICU) death and 12-month Cerebral Performance Category (CPC) were evaluated. In total, 82% of patients survived to ICU discharge and 48% had favorable neurological outcome at 1 year (CPC 1 or 2). At ICU admission, median plasma levels of hsCRP (2.8 mg/L) were normal, while levels of PTX3 (19.1 ng/mL) and sST2 (117 ng/mL) were markedly elevated. PTX3 and sST2 were higher in patients who developed MODS (p<0.0001). Admission levels of PTX3 and sST2 were also higher in patients who died in ICU and in those with an unfavorable 12-month neurological outcome (p<0.01). Admission levels of PTX3 and sST2 were independently associated with subsequent MODS [OR: 1.717 (1.221-2.414) and 1.340, (1.001-1.792), respectively] and with ICU death [OR: 1.536 (1.078-2.187) and 1.452 (1.064-1.981), respectively]. At 48 h, only sST2 and hsCRP were independently associated with ICU death. Higher plasma levels of PTX3 and sST2, but not of hsCRP, at ICU admission were associated with higher risk of MODS and early death.

  10. Stability of Markers Used for Real-Time Tumor Tracking After Percutaneous Intrapulmonary Placement

    SciTech Connect

    Voort van Zyp, Noelle C. van der; Hoogeman, Mischa S.; Water, Steven van de; Levendag, Peter C.; Holt, Bronno van der; Heijmen, Ben J.M.; Nuyttens, Joost J.

    2011-11-01

    Purpose: To determine the stability of markers used for real-time tumor tracking after percutaneous intrapulmonary placement. Methods and Materials: A total of 42 patients with 44 lesions, 111 markers, and {>=}2 repeat computed tomography (CT) scans were studied. The tumor on the repeat CT scans was registered with the tumor on the planning CT scan. Next, the three-dimensional marker coordinates were determined on the planning CT scan and repeat CT scans. Marker stability was analyzed by the displacement of the markers and the displacement of the center of mass (COM) of the marker configurations. In addition, we assessed the reliability of using the intermarker distance as a check for displacements in the COM of the marker configurations. Results: The median marker displacement was 1.3 mm (range, 0.1-53.6). The marker displacement was >5 mm in 12% of the markers and >10 mm in 5% of the markers. The causes of marker displacement >5 mm included marker migration (2 of 13) and target volume changes (5 of 13). Nonsynchronous tumor and marker movement during breathing might have been responsible for the displacements >5 mm in the other 6 of 13 markers. The median displacement in the COM of the marker configurations was 1.0 mm (range, 0.1-23.3). Displacements in the COM of the marker configurations of {>=}2.0 mm were detected by changes in the intermarker distance of >1.5 mm in 96% of the treatment fractions. Conclusion: The median marker displacement was small (1.3 mm). Nevertheless, displacements >5 mm occurred in 12% of the markers. Therefore, we recommend the implantation of multiple markers because multiple markers will enable a quick and reliable check of marker displacement by determining the change in the intermarker distance. A displacement in the COM of the marker configuration of {>=}2.0 mm was almost always detected (96%) by a change in the distance between the markers of >1.5 mm. This enabled the displaced marker to be disabled, such that tumor localization

  11. A genome scan for quantitative trait loci affecting milk somatic cell score in Israeli and Italian Holstein cows by means of selective DNA pooling with single- and multiple-marker mapping.

    PubMed

    Tal-Stein, R; Fontanesi, L; Dolezal, M; Scotti, E; Bagnato, A; Russo, V; Canavesi, F; Friedmann, A; Soller, M; Lipkin, E

    2010-10-01

    Mastitis is an important and common dairy cattle disease affecting milk yield, quality, and consumer safety as well as cheese yields and quality. Animal welfare and residues of the antibiotics used to treat mastitis cause public concern. Considerable genetic variation may allow selection for increased resistance to mastitis. Because of high genetic correlation to milk somatic cell score (SCS), SCS can serve as a surrogate trait for mastitis resistance. The present study intended to identify quantitative trait loci (QTL) affecting SCS in Israeli and Italian Holstein dairy cattle (IsH and ItH, respectively), using selective DNA pooling with single and multiple marker mapping. Milk samples of 4,788 daughters of 6 IsH and 7 ItH sires were used to construct sire-family high- and low-tail pools, which were genotyped at 123 (IsH) and 133 (ItH) microsatellite markers. Shadow correction was used to obtain pool allele frequency estimates. Frequency difference between the tails and empirical standard error of D, SE(D), were used to obtain P-values. All markers significant by single marker mapping were also significant by multiple marker mapping, but not vice versa. Combining both populations, 22 QTL on 21 chromosomes were identified; all corresponded to previous reports in the literature. Confidence intervals were set by chi-squared drop method. Heterozygosity of QTL was estimated at 44.2%. Allele substitution effects ranged from 1,782 to 4,930 cells/mL in estimated breeding value somatic cell count units. Most (80%) of the observed variation in estimated breeding value somatic cell score could be explained by the QTL identified under the stringent criteria. The results found here can be used as a basis for further genome-wide association studies for the same trait. Copyright © 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  12. Loss of heterozygosity (LOH) for markers on chromosome 8q in a human chondrosarcoma cell line and in a tumor that developed in a man with Hereditary Multiple Exostoses (HME)

    SciTech Connect

    Raskind, W.H.; Conrad, E.U.; Robbins, J.R.

    1994-09-01

    HME is an autosomal dominant disorder in which multiple benign cartilage-capped lesions develop on otherwise histologically normal bones. The majority of chondrosarcomas are sporadic, but the presence of HME greatly increases the risk to develop this tumor. Sarcoma may also arise in sporadically-occurring exostoses. The study of inherited disorders that predispose to malignant diseases has led to discoveries regarding molecular changes involved in carcinogenesis in general. In an analogous manner, somatic mutations in HME genes may be responsible for sporadic exostoses and/or chondrosarcomas. HME is genetically heterogeneous; EXT genes have been assigned to 8q24, the pericentromeric region of 11 and 19p11-p13. We compared chondrosarcoma cell DNA to DNA from white blood cells for LOH at polymorphic loci in these 3 regions. LOH for 4 of 5 markers in 8q24 was detected in a chondrosarcoma that arose in a man with HME. Heterozygosity was retained for markers and chromosomes 11 and 19. We then evaluated cultured cells from 10 sporadic chondrosarcomas. LOH for multiple markers in 8q24 was detected in a cell line, Ch-1, established from an aggressive tumor, but not in 9 other tumors. Of the 9 tumors studied, only the Ch-1 line exhibited LOH for chromosome 11 markers. LOH for a 19p marker was not detected in any of 6 tumors examined, including Ch-1. The karyotype of Ch-1 contains many structurally rearranged chromosomes. The two chromosome 11s appear normal but both chromosome 8 homologues have been replaced by der(8)t(5;8)(q22;q21.2). LOH at 8q24 was also detected in the uncultured tumor. These results suggest that genes responsible for HME may have tumor suppressor functions whose loss may be related to the development of a subset of chondrosarcomas.

  13. Analyzing subcomponents of affective dysregulation in borderline personality disorder in comparison to other clinical groups using multiple e-diary datasets.

    PubMed

    Santangelo, P S; Limberger, M F; Stiglmayr, C; Houben, M; Coosemans, J; Verleysen, G; Kuppens, P; Tuerlinckx, F; Vanpaemel, W; Ebner-Priemer, U W

    2016-01-01

    Affective dysregulation is widely regarded as being the core problem in patients with borderline personality disorder (BPD). Moreover, BPD is the disorder mainly associated with affective dysregulation. However, the empirical confirmation of the specificity of affective dysregulation for BPD is still pending. We used a validated approach from basic affective science that allows for simultaneously analyzing three interdependent components of affective dysregulation that are disturbed in patients with BPD: homebase, variability, and attractor strength (return to baseline). We applied two types of multilevel models on two e-diary datasets to investigate group differences regarding three subcomponents between BPD patients (n = 43; n = 51) and patients with posttraumatic stress disorder (PTSD; n = 28) and those with bulimia nervosa (BN; n = 20) as clinical control groups in dataset 1, and patients with panic disorder (PD; n = 26) and those with major depression (MD; n = 25) as clinical control groups in dataset 2. In addition, healthy controls (n = 28; n = 40) were included in the analyses. In both studies, e-diaries were used to repeatedly collect data about affective experiences during participants' daily lives. In study 1 a high-frequency sampling strategy with assessments in 15 min-intervals over 24 h was applied, whereas the assessments occurred every waking hour over 48 h in study 2. The local ethics committees approved both studies, and all participants provided written informed consent. In contradiction to our hypotheses, BPD patients did not consistently show altered affective dysregulation compared to the clinical patient groups. The only differences in affective dynamics in BPD patients emerged with regard to one of three subcomponents, affective homebase. However, these results were not even consistent. Conversely, comparing the patients to healthy controls revealed a pattern of more negative affective homebases, higher

  14. Construction of multiple recombinant SLA-I proteins by linking heavy chains and light chains in vitro and analyzing their secondary and 3-dimensional structures.

    PubMed

    Gao, Feng-shan; Bai, Jing; Zhang, Qiang; Xu, Chong-bo; Li, Yanmin

    2012-07-10

    Six breeds of swine were used to study the structure of swine leukocyte antigen class I (SLA-I). SLA-I complexes were produced by linking SLA-2 genes and β(2)m genes via a linker encoding a 15 amino acid glycine-rich sequence, (G4S)3, using splicing overlap extension (SOE)-PCR in vitro. The six recombinant SLA-2-linker-β(2)m genes were each inserted into p2X vectors and their expression induced in Escherichia coli TB1. The expressed proteins were detected by SDS-PAGE and western blotting. The maltose binding protein (MBP)-SLA-I fusion proteins were purified by amylose affinity chromatography followed by cleavage with factor Xa and separation of the SLA-I protein monomers from the MBP using a DEAE Ceramic Hyper D F column. The purified SLA-I monomers were detected by circular dichroism (CD) spectroscopy and the 3-dimensional (3D) structure of the constructed single-chain SLA-I molecules were analyzed by homology modeling. Recombinant SLA-2-Linker-β(2)m was successfully amplified from all six breeds of swine by SOE-PCR and expressed as fusion proteins of 84.1 kDa in pMAL-p2X, followed by confirmation by western blotting. After purification and cleavage of the MBP-SLA-I fusion proteins, SLA-I monomeric proteins of 41.6 kDa were separated. CD spectroscopy demonstrated that the SLA-I monomers had an α-helical structure, and the average α-helix, β-sheet, turn and random coil contents were 21.6%, 37.9%, 15.0% and 25.5%, respectively. Homology modeling of recombinant single-chain SLA-I molecules showed that the heavy chain and light chain constituted SLA-I complex with an open antigenic peptide-binding groove. It was concluded that the expressed SLA-I proteins in pMAL-p2X folded correctly and could be used to bind and screen nonameric peptides in vitro. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Aptamer induced multicoloured Au NCs-MoS2 "switch on" fluorescence resonance energy transfer biosensor for dual color simultaneous detection of multiple tumor markers by single wavelength excitation.

    PubMed

    Xu, Shenghao; Feng, Xiuying; Gao, Teng; Liu, Gufan; Mao, Yaning; Lin, Jiehua; Yu, Xijuan; Luo, Xiliang

    2017-08-29

    An aptamer induced "switch on" fluorescence resonance energy transfer (FRET) biosensor for the simultaneous detection of multiple tumor markers (e.g., AFP and CEA) combining molybdenum disulfide (MoS2) nanosheets with multicolored Au NCs by a single excitation was developed for the first time. Here, AFP aptamer functionalized green colored Au NCs (510 nm) and CEA aptamer functionalized red colored Au NCs (650 nm) are used as energy donors, while MoS2 is used as energy receptor. On the basis of recording the change of the recovered fluorescence intensity at 510 nm and 650 nm upon the addition of targets CEA and AFP, these two tumor markers can be simultaneously quantitatively detected, with detection limits of 0.16 and 0.21 ng mL(-1) (3σ) for AFP and CEA, respectively. In addition, it is noteworthy that the developed biosensor can not only realize accurate quantitative determination of multiple tumor markers by fluorescent intensity, but also be applied in semi-quantitative determination through photo visualization. More importantly, confocal microscope experiments prove that serums from normal and hepatoma patients can also be visually and qualitatively discriminated by this FRET-based biosensor with a single excitation wavelength, indicating promising potential of this assay for clinical diagnosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Tetrasomy 13q31.1qter due to an inverted duplicated neocentric marker chromosome in a fetus with multiple malformations.

    PubMed

    Haddad, Véronique; Aboura, Azzedine; Tosca, Lucie; Guediche, Narjes; Mas, Anne-Elisabeth; L'Herminé, Aurore Coulomb; Druart, Luc; Picone, Olivier; Brisset, Sophie; Tachdjian, Gérard

    2012-04-01

    Small supernumerary marker chromosome (sSMC) lacking alpha satellite DNA or endogenous centromere regions are rare and contain fully functional centromeres, called neocentromeres. We report on a woman with a 14-week gestation pregnancy with a cystic hygroma and cerebellar hypoplasia at ultrasound examination. Cytogenetic studies showed a karyotype 47,XY,+mar dn. This sSMC was observed in chorionic villi, lung, and muscle tissue. Array Comparative Genomic Hybridization showed a gain from 13q31.1 to 13qter region. Fluorescent in situ hybridization with pan alpha satellite probe and probes specific for chromosome 13 showed a marker corresponding to an inversion duplication of the 13q distal chromosomal region without alpha satellite DNA sequence, suggesting the presence of a neocentromere. Examination of the fetus showed dysmorphic features, cystic cervical hygroma, postaxial polydactyly of the right hand and left foot with short fingers, malrotation of the gut, and a micropenis with hypospadias. Genotype-phenotype correlation in tetrasomy 13q is discussed according to the four 13q chromosomal breakpoints reported (13q32, 13q31, 13q21, 13q14) for chromosome 13 supernumerary markers. Copyright © 2012 Wiley Periodicals, Inc.

  17. Use of a Time-of-Flight Camera With an Omek Beckon™ Framework to Analyze, Evaluate and Correct in Real Time the Verticality of Multiple Sclerosis Patients during Exercise

    PubMed Central

    Eguíluz, Gonzalo; García, María Begoña

    2013-01-01

    Any person with Multiple Sclerosis (MS), regardless of the severity of their disability, needs regular physical activity. Poorly performed exercises could aggravate muscle imbalances and worsen the patient’s health. In this paper, we propose a human body verticality detection system using a time-of-flight camera as a tool to detect incorrect postures and improve them in real time. The prototype uses Omek’s Beckon™ Framework to analyze and evaluate the position of patients during exercise. Preliminary results, based on objective questionnaires, indicate an improvement in patients’ evolution through better positions and performance of the exercises. PMID:24192790

  18. Visual Evoked Potential and Magnetic Resonance Imaging are More Effective Markers of Multiple Sclerosis Progression than Laser Polarimetry with Variable Corneal Compensation.

    PubMed

    Kantorová, Ema; Ziak, Peter; Kurča, Egon; Koyšová, Mária; Hladká, Mária; Zeleňák, Kamil; Michalik, Jozef

    2014-01-01

    The aim of our study was to assess the role of laser polarimetry and visual evoked potentials (VEP) as potential biomarkers of disease progression in multiple sclerosis (MS). A total of 41 patients with MS (82 eyes) and 22 age-related healthy volunteers (44 eyes) completed the study. MS patients were divided into two groups, one (ON) with a history of optic neuritis (17 patients, 34 eyes) and another group (NON) without it (24 patients, 48 eyes). The MS patients and controls underwent laser polarimetry (GDx) examination of the retinal nerve fiber layer (RNFL). In the MS group, we also examined: Kurtzke "expanded disability status scale" (EDSS), the duration of the disorder, VEP - latency and amplitude, and conventional brain magnetic resonance imaging (MRI). Our results were statistically analyzed using ANOVA, Mann-Whitney, and Spearman correlation analyses. In the MS group, brain atrophy and new T2 brain lesions in MRI correlated with both VEP latencies and amplitudes. Separate comparisons revealed VEP latency testing to be less sensitive in ON than in NON-patients. In ON patients, VEP amplitudes correlated mildly with brain atrophy (r = -0.15) and strongly with brain new MRI lesions (r = -0.8). In NON-patients, highly significant correlation of new MRI brain lesions with VEP latencies (r = 0.63, r = 0.6) and amplitudes (r = -0.3, r = -4.2) was found. EDSS also correlated with brain atrophy in this group (r = 0.5). Our study did not find a correlation of GDx measures with MRI tests. The GDx method was not able to detect whole brain demyelinization and the degeneration process, but was only able to reveal the involvement of optic nerves in ON and NON-patients. In our study, we found that both methods (VEP and GDx) can be used for the detection of optic nerve damage, but VEP was found to be superior in evaluating whole brain demyelinization and axonal degeneration. Both VEP and MRI, but not GDx, have an important role in monitoring

  19. Visual Evoked Potential and Magnetic Resonance Imaging are More Effective Markers of Multiple Sclerosis Progression than Laser Polarimetry with Variable Corneal Compensation

    PubMed Central

    Kantorová, Ema; Žiak, Peter; Kurča, Egon; Koyšová, Mária; Hladká, Mária; Zeleňák, Kamil; Michalik, Jozef

    2014-01-01

    Background: The aim of our study was to assess the role of laser polarimetry and visual evoked potentials (VEP) as potential biomarkers of disease progression in multiple sclerosis (MS). Participants: A total of 41 patients with MS (82 eyes) and 22 age-related healthy volunteers (44 eyes) completed the study. MS patients were divided into two groups, one (ON) with a history of optic neuritis (17 patients, 34 eyes) and another group (NON) without it (24 patients, 48 eyes). The MS patients and controls underwent laser polarimetry (GDx) examination of the retinal nerve fiber layer (RNFL). In the MS group, we also examined: Kurtzke “expanded disability status scale” (EDSS), the duration of the disorder, VEP – latency and amplitude, and conventional brain magnetic resonance imaging (MRI). Our results were statistically analyzed using ANOVA, Mann–Whitney, and Spearman correlation analyses. Results: In the MS group, brain atrophy and new T2 brain lesions in MRI correlated with both VEP latencies and amplitudes. Separate comparisons revealed VEP latency testing to be less sensitive in ON than in NON-patients. In ON patients, VEP amplitudes correlated mildly with brain atrophy (r = −0.15) and strongly with brain new MRI lesions (r = −0.8). In NON-patients, highly significant correlation of new MRI brain lesions with VEP latencies (r = 0.63, r = 0.6) and amplitudes (r = −0.3, r = −4.2) was found. EDSS also correlated with brain atrophy in this group (r = 0.5). Our study did not find a correlation of GDx measures with MRI tests. The GDx method was not able to detect whole brain demyelinization and the degeneration process, but was only able to reveal the involvement of optic nerves in ON and NON-patients. Conclusion: In our study, we found that both methods (VEP and GDx) can be used for the detection of optic nerve damage, but VEP was found to be superior in evaluating whole brain demyelinization and axonal degeneration. Both VEP

  20. Grave Markers.

    ERIC Educational Resources Information Center

    DeMuro, Ted

    1985-01-01

    Junior high school students studied the cultural uses, symbolic meanings, and general physical forms of tombs and tombstones and then used basic slab building techniques to construct large clay grave markers. (RM)

  1. Bone Markers

    MedlinePlus

    ... from the amino terminal end of the protein matrix; another marker used to monitor therapy. Deoxypyridinoline (DPD) – a collagen breakdown product with a ring structure. Pyridinium Crosslinks – a group of collagen breakdown products ...

  2. Serum soluble interleukin-2 receptor level is more sensitive than angiotensin-converting enzyme or lysozyme for diagnosis of sarcoidosis and may be a marker of multiple organ involvement.

    PubMed

    Thi Hong Nguyen, Chuyen; Kambe, Naotomo; Kishimoto, Izumi; Ueda-Hayakawa, Ikuko; Okamoto, Hiroyuki

    2017-03-11

    Skin lesions in sarcoidosis are often the initial symptoms that enable the dermatologist to be the first to diagnose this granulomatosis. However, diagnosis is sometimes very problematic. In 2015, the diagnostic criteria for sarcoidosis were updated in Japan, with elevated serum soluble interleukin-2 receptor (sIL-2R) replacing negative tuberculin reaction. Therefore, we assessed the clinical utility of sIL-2R compared with two other common markers, angiotensin-converting enzyme (ACE) and lysozyme, in patients who visited the dermatology clinic. Data from 72 patients showed that sIL-2R was more sensitive than both ACE and lysozyme in supporting a diagnosis of sarcoidosis (52.8%) compared with ACE (29%) and lysozyme (26.4%). Additionally, the sIL-2R level was significantly higher in patients with multiple organ involvement and parenchymal infiltration. Patients with elevated sIL-2R levels had higher serum ACE and lysozyme levels, a higher incidence of pulmonary involvement, more severe chest radiographic stage and a high incidence of expression-specific signs by imaging analysis. Receiver-operator curve analysis showed that sIL-2R was a better marker at the threshold cut-off point compared with ACE and lysozyme for identifying patients with multiple organ involvement, detecting patients with pulmonary disease and parenchymal infiltration as well as predicting the presence of specific signs in the diagnosis of sarcoidosis. Moreover, the kinetics of sIL-2R levels correlated closely with clinical manifestations, in contrast to the modest changes of ACE and lysozyme levels during the follow-up period. In conclusion, sIL-2R may be considered a good marker for diagnosis and a potential indicator of disease activity.

  3. SSR markers for Quercus suber tree identification and embryo analysis.

    PubMed

    Gómez, A; Pintos, B; Aguiriano, E; Manzanera, J A; Bueno, M A

    2001-01-01

    Three Quercus simple sequence repeat (SSR) markers were amplified by polymerase chain reaction (PCR) from nuclear DNA extracts of trees and in vitro-induced haploid embryos from anther cultures of Quercus suber L. These markers were sufficiently polymorphic to identify 10 of 12 trees located in two Spanish natural areas. The same loci have been analyzed in anther-derived haploid embryos showing the parental tree allele segregation. All the alleles were present in the haploid progeny. The presence of diverse alleles in embryos derived from the same anther demonstrated that they were induced on multiple microspores or pollen grains and they were not clonally propagated. Also, diploid cultures and mixtures of haploid-diploid tissues were obtained. The origin of such cultures, either somatic or gametic, was elucidated by SSR markers. All the embryos showed only one allele, corroborating a haploid origin. Allelic composition of the haploid progeny permitted parental identification among all analyzed trees.

  4. Efficiency of typing unaffected relatives in an affected-sib-pair linkage study with single-locus and multiple tightly linked markers

    SciTech Connect

    Holmans, P.; Clayton, D.

    1995-11-01

    In an affected-sib-pair study, the parents are often unavailable for typing, particularly for diseases of late onset. In many cases, however, it is possible to sample unaffected siblings. It is therefore desirable to assess the contribution of such siblings to the power of such a study. The likelihood ratio introduced by Risch and improved by Holmans was extended to incorporate data from unaffected siblings. Tests based on two likelihoods were considered: the full likelihood of the data, based on the identity-by-descent (IBD) sharing states of the entire sibship, and a pseudolikelihood based on the IBD sharing states of the affected pair only, using the unaffected siblings to infer parental genotypes. The latter approach was found to be more powerful, except when penetrance was high. Typing an unaffected sibling, or just one parent, was found to give only a small increase in power except when the PIC of the marker was low. Even then, typing an unaffected relative increased the overall number of individuals that had to be typed to achieve a given power. If there is no highly informative marker locus in the area under study, it may be possible to {open_quotes}build{close_quotes} one by combining the alleles from two or more neighboring tightly linked loci into haplotypes. Typing two loci gave a sizeable power increase over a single locus, but typing further loci gave much smaller gains. Building haplotypes will introduce phase uncertainties, with the result that such a system will yield less power than will a single locus with the same number of alleles. This power loss was small, however, and did not affect the conclusions regarding the worth of typing unaffected relatives. 14 refs., 2 figs., 11 tabs.

  5. Prediction of the effect of atrasentan on renal and heart failure outcomes based on short-term changes in multiple risk markers.

    PubMed

    Schievink, Bauke; de Zeeuw, Dick; Smink, Paul A; Andress, Dennis; Brennan, John J; Coll, Blai; Correa-Rotter, Ricardo; Hou, Fan Fan; Kohan, Donald; Kitzman, Dalane W; Makino, Hirofumi; Parving, Hans-Henrik; Perkovic, Vlado; Remuzzi, Giuseppe; Tobe, Sheldon; Toto, Robert; Hoekman, Jarno; Lambers Heerspink, Hiddo J

    2016-05-01

    A recent phase II clinical trial (Reducing Residual Albuminuria in Subjects with Diabetes and Nephropathy with AtRasentan trial and an identical trial in Japan (RADAR/JAPAN)) showed that the endothelin A receptor antagonist atrasentan lowers albuminuria, blood pressure, cholesterol, hemoglobin, and increases body weight in patients with type 2 diabetes and nephropathy. We previously developed an algorithm, the Parameter Response Efficacy (PRE) score, which translates short-term drug effects into predictions of long-term effects on clinical outcomes. We used the PRE score on data from the RADAR/JAPAN study to predict the effect of atrasentan on renal and heart failure outcomes. We performed a post-hoc analysis of the RADAR/JAPAN randomized clinical trials in which 211 patients with type-2 diabetes and nephropathy were randomly assigned to atrasentan 0.75 mg/day, 1.25 mg/day, or placebo. A PRE score was developed in a background set of completed clinical trials using multivariate Cox models. The score was applied to baseline and week-12 risk marker levels of RADAR/JAPAN participants, to predict atrasentan effects on clinical outcomes. Outcomes were defined as doubling serum creatinine or end-stage renal disease and hospitalization for heart failure. The PRE score predicted renal risk changes of -23% and -30% for atrasentan 0.75 and 1.25 mg/day, respectively. PRE scores also predicted a small non-significant increase in heart failure risk for atrasentan 0.75 and 1.25 mg/day (+2% vs. +7%). Selecting patients with >30% albuminuria reduction from baseline (responders) improved renal outcome to almost 50% risk reduction, whereas non-responders showed no renal benefit. Based on the RADAR/JAPAN study, with short-term changes in risk markers, atrasentan is expected to decrease renal risk without increased risk of heart failure. Within this population albuminuria responders appear to contribute to the predicted improvements, whereas non-responders showed no benefit

  6. Use of multiple markers demonstrates a cryptic western refugium and postglacial colonisation routes of Atlantic salmon (Salmo salar L.) in Northwest Europe.

    PubMed

    Finnegan, A K; Griffiths, A M; King, R A; Machado-Schiaffino, G; Porcher, J-P; Garcia-Vazquez, E; Bright, D; Stevens, J R

    2013-07-01

    Glacial and postglacial processes are known to be important determinants of contemporary population structuring for many species. In Europe, refugia in the Italian, Balkan and Iberian peninsulas are believed to be the main sources of species colonising northern Europe after the glacial retreat; however, there is increasing evidence of small, cryptic refugia existing north of these for many cold-tolerant species. This study examined the glacial history of Atlantic salmon in western Europe using two independent classes of molecular markers, microsatellites (nuclear) and mitochondrial DNA variation. Alongside the well-documented refuge in the Iberian Peninsula, evidence for a cryptic refuge in northwest France is also presented. Critically, methods utilised to estimate divergence times between the refugia indicated that salmon in these two regions had diverged a long time before the last glacial maximum; coalescence analysis (as implemented in the program IMa2) estimated divergence times at around 60 000 years before present. Through the examination of haplotype frequencies, previously glaciated areas of northwest Europe, that is, Britain and Ireland, appear to have been colonised from salmon expanding out of both refugia, with the southwest of England being the primary contact zone and exhibiting the highest genetic diversity.

  7. Use of multiple markers demonstrates a cryptic western refugium and postglacial colonisation routes of Atlantic salmon (Salmo salar L.) in northwest Europe

    PubMed Central

    Finnegan, A K; Griffiths, A M; King, R A; Machado-Schiaffino, G; Porcher, J-P; Garcia-Vazquez, E; Bright, D; Stevens, J R

    2013-01-01

    Glacial and postglacial processes are known to be important determinants of contemporary population structuring for many species. In Europe, refugia in the Italian, Balkan and Iberian peninsulas are believed to be the main sources of species colonising northern Europe after the glacial retreat; however, there is increasing evidence of small, cryptic refugia existing north of these for many cold-tolerant species. This study examined the glacial history of Atlantic salmon in western Europe using two independent classes of molecular markers, microsatellites (nuclear) and mitochondrial DNA variation. Alongside the well-documented refuge in the Iberian Peninsula, evidence for a cryptic refuge in northwest France is also presented. Critically, methods utilised to estimate divergence times between the refugia indicated that salmon in these two regions had diverged a long time before the last glacial maximum; coalescence analysis (as implemented in the program IMa2) estimated divergence times at around 60 000 years before present. Through the examination of haplotype frequencies, previously glaciated areas of northwest Europe, that is, Britain and Ireland, appear to have been colonised from salmon expanding out of both refugia, with the southwest of England being the primary contact zone and exhibiting the highest genetic diversity. PMID:23512011

  8. Alteration of Multiple Leukocyte Gene Expression Networks is Linked with Magnetic Resonance Markers of Prognosis After Acute ST-Elevation Myocardial Infarction

    PubMed Central

    Teren, A.; Kirsten, H.; Beutner, F.; Scholz, M.; Holdt, L. M.; Teupser, D.; Gutberlet, M.; Thiery, J.; Schuler, G.; Eitel, I.

    2017-01-01

    Prognostic relevant pathways of leukocyte involvement in human myocardial ischemic-reperfusion injury are largely unknown. We enrolled 136 patients with ST-elevation myocardial infarction (STEMI) after primary angioplasty within 12 h after onset of symptoms. Following reperfusion, whole blood was collected within a median time interval of 20 h (interquartile range: 15–25 h) for genome-wide gene expression analysis. Subsequent CMR scans were performed using a standard protocol to determine infarct size (IS), area at risk (AAR), myocardial salvage index (MSI) and the extent of late microvascular obstruction (lateMO). We found 398 genes associated with lateMO and two genes with IS. Neither AAR, nor MSI showed significant correlations with gene expression. Genes correlating with lateMO were strongly related to several canonical pathways, including positive regulation of T-cell activation (p = 3.44 × 10−5), and regulation of inflammatory response (p = 1.86 × 10−3). Network analysis of multiple gene expression alterations associated with larger lateMO identified the following functional consequences: facilitated utilisation and decreased concentration of free fatty acid, repressed cell differentiation, enhanced phagocyte movement, increased cell death, vascular disease and compensatory vasculogenesis. In conclusion, the extent of lateMO after acute, reperfused STEMI correlated with altered activation of multiple genes related to fatty acid utilisation, lymphocyte differentiation, phagocyte mobilisation, cell survival, and vascular dysfunction. PMID:28155873

  9. Neutralizing antibodies, MxA expression and MMP-9/TIMP-1 ratio as markers of bioavailability of interferon-beta treatment in multiple sclerosis patients: a two-year follow-up study.

    PubMed

    Garcia-Montojo, M; Dominguez-Mozo, M I; de las Heras, V; Bartolome, M; Garcia-Martinez, A; Arroyo, R; Alvarez-Lafuente, R

    2010-03-01

    The objective of this study was to correlate the detection of neutralizing antibodies (NAbs) by the cytopathic effect (CPE) assay, with the expression of myxovirus resistance protein A (MxA), and the ratio between matrix metalloproteinase 9 (MMP-9) and its tissular inhibitor (TIMP-1), in order to evaluate their usefulness as markers of interferon beta (IFN-beta) bioavailability. Pairs of blood and serum samples were collected from 50 patients with multiple sclerosis (MS) during 2 years of IFN-beta treatment. Expression of MxA, MMP-9 and TIMP-1 were analysed by quantitative PCR, and NAbs were measured by CPE assay. During the study, 60% of patients presented NAbs. The number of serum samples that were NAbs+ was significantly increased amongst patients with relapses (41/92 vs. 33/108, P = 0.04). With one serum sample and with a NAb titre >100 tenfold reduction unit (TRU), 66.7% of patients with MS suffered from relapses, 41.7% suffered from progression, and 75% was not an optimal clinical responder. We did not find any significant difference in MxA. We found that 62.5% of patients with MS patients whose ratio was increased twofold after 2 years suffered from relapses, 37.5% suffered from progression, and 68.7% was not an optimal clinical responder. The early detection of NAbs by CPE assay and the finding of only one serum sample with a NAb titre >100 TRU seem to be markers of low bioavailability of IFN-beta, whilst a twofold decrease in the MMP-9/TIMP-1 ratio by quantitative PCR assay seems to be a marker of high bioavailability of IFN-beta.

  10. Accuracy of marker analysis, quantitative real-time polymerase chain reaction, and multiple ligation-dependent probe amplification to determine SMN2 copy number in patients with spinal muscular atrophy.

    PubMed

    Alías, Laura; Bernal, Sara; Barceló, Maria J; Also-Rallo, Eva; Martínez-Hernández, Rebeca; Rodríguez-Alvarez, Francisco J; Hernández-Chico, Concepción; Baiget, Montserrat; Tizzano, Eduardo F

    2011-09-01

    Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by absence of or mutations in the survival motor neuron1 gene (SMN1). All SMA patients have a highly homologous copy of SMN1, the SMN2 gene. Severe (type I) SMA patients present one or two SMN2 copies, whereas milder chronic forms (type II-III) usually have three or four SMN2 copies. SMN2 dosage is important to stratify patients for motor function tests and clinical trials. Our aim was to compare three methods, marker analysis, real-time quantitative polymerase chain reaction using the LightCycler instrument, and multiple ligation-dependent probe amplification (MLPA), to characterize their accuracy in quantifying SMN2 genes. We studied a group of 62 genetically confirmed SMA patients, 54 with homozygous absence of exons 7 and 8 of SMN1 and 8 with SMN2-SMN1 hybrid genes. A complete correlation using the three methods was observed in 32 patients (51.6%). In the remaining 30 patients, discordances between the three methods were found, including under or overestimation of SMN2 copies by marker analysis with respect to the quantitative methods (LightCycler and MLPA) because of lack of informativeness of markers, 3' deletions of SMN genes, and breakpoints in SMN2-SMN1 hybrid genes. The technical limitations and advantages and disadvantages of these methods are discussed. We conclude that the three methods complement each other in estimating the SMN2 copy number in most cases. However, MLPA offers additional information to characterize SMA cases with particular rearrangements such as partial deletions and hybrid genes.

  11. Recovery of polyclonal immunoglobulins one year after autologous stem cell transplantation as a long-term predictor marker of progression and survival in multiple myeloma.

    PubMed

    González-Calle, Verónica; Cerdá, Seila; Labrador, Jorge; Sobejano, Eduardo; González-Mena, Beatriz; Aguilera, Carmen; Ocio, Enrique María; Vidriales, María Belén; Puig, Noemí; Gutiérrez, Norma Carmen; Garcĺa-Sanz, Ramón; Alonso, Jose' Marĺa; López, Rosa; Aguilar, Carlos; Garcĺa de Coca, Alfonso; Hernández, Roberto; Hernández, José Mariano; Escalante, Fernando; Mateos, María-Victoria

    2017-01-25

    Immunoparesis or suppression of polyclonal immunoglobulins is a very common condition in newly diagnosed myeloma patients. However, the recovery of polyclonal immunoglobulins in the setting of immune reconstitution after autologous stem cell transplantation and its effect on outcome has not been explored to date. We conducted this study in a cohort of 295 patients who had undergone autologous transplantation. In order to explore the potential role of immunoglubulin recovery as a dynamic predictor of progression or survival after transplantation, conditional probabilities of progression-free survival and overall survival were estimated, according to immunoglobulin recovery, at different time points using a landmark approach. One year after transplant, when B-cell reconstitution is expected to be completed, among 169 patients alive and progression-free, 88 patients (52%) had recovered immunoglobulins and 81 (48%) had not. Interestingly, the group with immunoglobulin recovery had a significantly longer median progression-free survival than the group with persistent immunoparesis (median 60.4 vs. 27.9 months, respectively; hazard ratio=0.45, 95% CI: 0.31-0.66; P<0.001), and improved overall survival (11.3 vs.7.3 years; hazard ratio=0.45, 95% CI=0.27-0.74, P=0.002). Furthermore, the percentage of normal plasma cells detected by flow cytometry in the bone marrow assessed at day 100 after transplantation was associated with the immunoglobulin recovery at that time and may predict immunoglobulin recovery in the subsequent months: 9 months and 1 year. In conclusion, the recovery of polyclonal immunoglobulins 1 year after autologous transplantation in myeloma patients is an independent long-term predictor marker for progression and survival.

  12. Herbs and spices: characterization and quantitation of biologically-active markers for routine quality control by multiple headspace solid-phase microextraction combined with separative or non-separative analysis.

    PubMed

    Sgorbini, Barbara; Bicchi, Carlo; Cagliero, Cecilia; Cordero, Chiara; Liberto, Erica; Rubiolo, Patrizia

    2015-01-09

    Herbs and spices are used worldwide as food flavoring, thus determination of their identity, origin, and quality is mandatory for safe human consumption. An analysis strategy based on separative (HS-SPME-GC-MS) and non-separative (HS-SPME-MS) approaches is proposed for the volatile fraction of herbs and spices, for quality control and to quantify the aromatic markers with a single analysis directly on the plant material as such. Eight-to-ten lots of each of the following herbs/spices were considered: cloves (Syzygium aromaticum (L.) Merr. & Perry), American peppertree (Schinus molle L.), black pepper and white pepper (Piper nigrum L.), rosemary (Rosmarinus officinalis L.), sage (Salvia officinalis L.) and thyme (Thymus vulgaris L.). Homogeneity, origin, and chemotypes of the investigated lots of each herb/spice were defined by fingerprinting, through statistical elaboration with principal component analysis (PCA). Characterizing aromatic markers were directly quantified on the solid matrix through multiple headspace extraction-HS-SPME (MHS-SPME). Reliable results were obtained with both separative and non-separative methods (where the latter were applicable); the two were in full agreement, RSD% ranging from 1.8 to 7.7% for eugenol in cloves, 2.2-18.4% for carvacrol+thymol in thyme, and 3.1-16.8% for thujones in sage.

  13. Identification of a novel putative gastrointestinal stem cell and adenoma stem cell marker, doublecortin and CaM kinase-like-1, following radiation injury and in adenomatous polyposis coli/multiple intestinal neoplasia mice.

    PubMed

    May, Randal; Riehl, Terrence E; Hunt, Clayton; Sureban, Sripathi M; Anant, Shrikant; Houchen, Courtney W

    2008-03-01

    In the gut, tumorigenesis arises from intestinal or colonic crypt stem cells. Currently, no definitive markers exist that reliably identify gut stem cells. Here, we used the putative stem cell marker doublecortin and CaM kinase-like-1 (DCAMKL-1) to examine radiation-induced stem cell apoptosis and adenomatous polyposis coli (APC)/multiple intestinal neoplasia (min) mice to determine the effects of APC mutation on DCAMKL-1 expression. Immunoreactive DCAMKL-1 staining was demonstrated in the intestinal stem cell zone. Furthermore, we observed apoptosis of the cells negative for DCAMKL-1 at 6 hours. We found DNA damage in all the cells in the crypt region, including the DCAMKL-1-positive cells. We also observed stem cell apoptosis and mitotic DCAMKL-1-expressing cells 24 hours after irradiation. Moreover, in APC/min mice, DCAMKL-1-expressing cells were negative for proliferating cell nuclear antigen and nuclear beta-catenin in normal-appearing intestine. However, beta-catenin was nuclear in DCAMKL-1-positive cells in adenomas. Thus, nuclear translocation of beta-catenin distinguishes normal and adenoma stem cells. Targeting DCAMKL-1 may represent a strategy for developing novel chemotherapeutic agents.

  14. The investigation on the location effect of external markers in respiratory-gated radiotherapy.

    PubMed

    Yan, Hui; Zhu, Guopei; Yang, James; Lu, Mei; Ajlouni, Munther; Kim, Jae Ho; Yin, Fang-Fang

    2008-04-16

    To investigate the effect of the marker placement on the correlation relationship between the motions of external markers and the internal target under different breathing patterns for several lung cancer patients. To monitor and record simultaneous motions of internal target and associated surrogate markers during respiratory gated radiotherapy, an infrared camera system synchronized with a medical simulator was installed in our institute. Multiple external markers were placed on the patients' chest wall with proper geometrical arrangement in closely monitoring the motion of skin near tumor. The motion signals of three breathing sessions (free breathing, breath-holding, and free breathing after breath-holding) were recorded and the quality of correlation between them was analyzed. For a single marker motion, its correlation with the internal target was analyzed using cross-covariance function. For the multiple markers, their correlation with the internal target was analyzed based on additive model. Seven patients undergoing radiotherapy with right upper or middle lobe lesions were enrolled in this study. Statistic analysis based on the internal-external motion signals shows that the effect of marker location on the quality of its correlation with the internal target is varied from patient to patient. There was no specific marker location where consistently demonstrated superior quality of correlation with the internal target motion over three breathing sessions for all patients. As the composite surrogate signal which was generated from the motions of multiple external markers was used to correlate the internal target motion, significant improvement of the quality of correlation was achieved. The correlation of external marker to the internal target could be influenced by several factors such as patient population, marker locations, and breathing patterns, considerably. The quality of correlation and predictability to the internal target furnished by a single

  15. Comparison of the sagittal sinus cross-sectional area between patients with multiple sclerosis, hydrocephalus, intracranial hypertension and spontaneous intracranial hypotension: a surrogate marker of venous transmural pressure?

    PubMed

    Bateman, Grant A; Lechner-Scott, Jeannette; Copping, Ross; Moeskops, Christopher; Yap, Swee Leong

    2017-07-06

    There is evidence that patients with multiple sclerosis (MS) and hydrocephalus share some common pathophysiological mechanisms. Alterations in CSF pressure are known to affect cerebral venous sinus geometry. To further explore these mechanisms, we measured the superior sagittal sinus (SSS) cross-sectional area 3 cm above the torcular using T2 images in 20 MS, 10 spontaneous intracranial hypotension (SIH), 21 hydrocephalus and 20 idiopathic intracranial hypertension (IIH) patients and compared with 20 matched controls. The SSS area was reduced by 25% in hydrocephalus (p = 0.0008), increased by 22% (p = 0.037) in SIH and unchanged in IIH compared to matched controls. In MS there was a 16% increase in SSS area (p = 0.01).The findings suggest that changes in SSS cross-sectional are common between MS and SIH patients, while in hydrocephalus and IIH these are different.

  16. The microRNA-200 family targets multiple non-small cell lung cancer prognostic markers in H1299 cells and BEAS-2B cells.

    PubMed

    Pacurari, Maricica; Addison, Joseph B; Bondalapati, Naveen; Wan, Ying-Wooi; Luo, Dajie; Qian, Yong; Castranova, Vincent; Ivanov, Alexey V; Guo, Nancy Lan

    2013-08-01

    Lung cancer remains the leading cause of cancer-related mortality for both men and women. Tumor recurrence and metastasis is the major cause of lung cancer treatment failure and death. The microRNA‑200 (miR-200) family is a powerful regulator of the epithelial-mesenchymal transition (EMT) process, which is essential in tumor metastasis. Nevertheless, miR-200 family target genes that promote metastasis in non-small cell lung cancer (NSCLC) remain largely unknown. Here, we sought to investigate whether the microRNA-200 family regulates our previously identified NSCLC prognostic marker genes associated with metastasis, as potential molecular targets. Novel miRNA targets were predicted using bioinformatics tools based on correlation analyses of miRNA and mRNA expression in 57 squamous cell lung cancer tumor samples. The predicted target genes were validated with quantitative RT-PCR assays and western blot analysis following re-expression of miR-200a, -200b and -200c in the metastatic NSCLC H1299 cell line. The results show that restoring miR-200a or miR-200c in H1299 cells induces downregulation of DLC1, ATRX and HFE. Reinforced miR-200b expression results in downregulation of DLC1, HNRNPA3 and HFE. Additionally, miR-200 family downregulates HNRNPR3, HFE and ATRX in BEAS-2B immortalized lung epithelial cells in quantitative RT-PCR and western blot assays. The miR-200 family and these potential targets are functionally involved in canonical pathways of immune response, molecular mechanisms of cancer, metastasis signaling, cell-cell communication, proliferation and DNA repair in Ingenuity pathway analysis (IPA). These results indicate that re-expression of miR-200 downregulates our previously identified NSCLC prognostic biomarkers in metastatic NSCLC cells. These results provide new insights into miR-200 regulation in lung cancer metastasis and consequent clinical outcome, and may provide a potential basis for innovative therapeutic approaches for the treatment of this

  17. & Source apportionment of particulate matter in the United States and associations with lung inflammatory Markers

    EPA Science Inventory

    Size-fractionated particulate matter (PM) samples were collected from six U.S. cities and chemically analyzed as part of the Multiple Air Pollutant Study. Particles were administered to cultured lung cells and the production of three different proinflammatory markers was measured...

  18. & Source apportionment of particulate matter in the United States and associations with lung inflammatory Markers

    EPA Science Inventory

    Size-fractionated particulate matter (PM) samples were collected from six U.S. cities and chemically analyzed as part of the Multiple Air Pollutant Study. Particles were administered to cultured lung cells and the production of three different proinflammatory markers was measured...

  19. Markers of oxidative/nitrative damage of plasma proteins correlated with EDSS and BDI scores in patients with secondary progressive multiple sclerosis.

    PubMed

    Morel, Agnieszka; Bijak, Michał; Niwald, Marta; Miller, Elżbieta; Saluk, Joanna

    2017-05-19

    Objectives The objective of the present study was to evaluate oxidative/nitrative stress in the plasma of 50 patients suffering from the secondary progressive course of multiple sclerosis (MS), and to verify its correlation with physical and mental disability as assessed by the Expanded Disability Status Scale (EDSS), and the Beck Depression Inventory (BDI). Methods Oxidative and nitrative damage to proteins was determined by the level of carbonyl groups and 3-nitrotyrosine using ELISA test. Based on the reaction with Ellman's reagent, we estimated the concentration of oxidized thiol groups. Additionally, we measured the level of lipid peroxidation. Results In plasma drawn from MS patients, we observed a significantly higher level of 3-NT (92%; P < 0.0003), carbonyl groups (29%; P < 0.0001) and thiobarbituric acid reactive substances (73%; P < 0.0001), as well as a lower concentration of thiol groups (33%; P < 0.0001), in comparison to healthy subjects. We noted positive correlations between the level of carbonyl groups or 3-NT and both diagnostic parameters, EDSS and BDI. Negative correlations were observed between concentration of -SH groups and EDSS and BDI. Conclusion Our results indicate that impaired red-ox balance can significantly promote neurodegeneration in secondary progressive MS.

  20. Thalidomide-prednisone maintenance following autologous stem cell transplant for multiple myeloma: effect on thrombin generation and procoagulant markers in NCIC CTG MY.10.

    PubMed

    Kovacs, Michael J; Davies, Gwynivere A; Chapman, Judy-Anne W; Bahlis, Nizar; Voralia, Michael; Roy, Jean; Kouroukis, C Tom; Chen, Christine; Belch, Andrew; Reece, Donna; Zhu, Liting; Meyer, Ralph M; Shepherd, Lois; Stewart, Keith A

    2015-02-01

    Venous thromboembolism (VTE) has an increased incidence in patients with multiple myeloma (MM), especially during chemotherapy. Mechanisms including upregulation of procoagulant factors, such as factor VIII, have been postulated. The National Cancer Institute of Canada Clinical Trials Group MY.10 phase III clinical trial compared thalidomide-prednisone to observation for 332 patients with MM post-autologous stem cell transplantation (ASCT), with a primary endpoint of overall survival and various secondary endpoints including the incidence of VTE. One hundred and fifty-three patients had biomarker data, including D-dimer, factor VIII and thrombin anti-thrombin (TAT) levels collected post-ASCT at baseline and 2 months after intervention investigating in-vivo thrombin generation. Differences between the time-points included a significant reduction over time in D-dimer, factor VIII and TAT levels in the observation group and sustained elevation of D-dimer, significant increase in factor VIII and reduction in TAT levels in the thalidomide-prednisone group. Eight VTE events were reported in this subset of study patients, all in the thalidomide-prednisone arm, with a trend to increase in D-dimer levels over time in those patients with VTE. This study provides physiological and clinical evidence for an increased risk of VTE associated with thalidomide-prednisone maintenance therapy post-ASCT for MM.

  1. In vivo nanoparticle imaging of innate immune cells can serve as a marker of disease severity in a model of multiple sclerosis.

    PubMed

    Kirschbaum, Klara; Sonner, Jana K; Zeller, Matthias W; Deumelandt, Katrin; Bode, Julia; Sharma, Rakesh; Krüwel, Thomas; Fischer, Manuel; Hoffmann, Angelika; Costa da Silva, Milene; Muckenthaler, Martina U; Wick, Wolfgang; Tews, Björn; Chen, John W; Heiland, Sabine; Bendszus, Martin; Platten, Michael; Breckwoldt, Michael O

    2016-11-15

    Innate immune cells play a key role in the pathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). Current clinical imaging is restricted to visualizing secondary effects of inflammation, such as gliosis and blood-brain barrier disruption. Advanced molecular imaging, such as iron oxide nanoparticle imaging, can allow direct imaging of cellular and molecular activity, but the exact cell types that phagocytose nanoparticles in vivo and how phagocytic activity relates to disease severity is not well understood. In this study we used MRI to map inflammatory infiltrates using high-field MRI and fluorescently labeled cross-linked iron oxide nanoparticles for cell tracking. We confirmed nanoparticle uptake and MR detectability ex vivo. Using in vivo MRI, we identified extensive nanoparticle signal in the cerebellar white matter and circumscribed cortical gray matter lesions that developed during the disease course (4.6-fold increase of nanoparticle accumulation in EAE compared with healthy controls, P < 0.001). Nanoparticles showed good cellular specificity for innate immune cells in vivo, labeling activated microglia, infiltrating macrophages, and neutrophils, whereas there was only sparse uptake by adaptive immune cells. Importantly, nanoparticle signal correlated better with clinical disease than conventional gadolinium (Gd) imaging (r, 0.83 for nanoparticles vs. 0.71 for Gd-imaging, P < 0.001). We validated our approach using the Food and Drug Administration-approved iron oxide nanoparticle ferumoxytol. Our results show that noninvasive molecular imaging of innate immune responses can serve as an imaging biomarker of disease activity in autoimmune-mediated neuroinflammation with potential clinical applications in a wide range of inflammatory diseases.

  2. Different sleep onset criteria at the multiple sleep latency test (MSLT): an additional marker to differentiate central nervous system (CNS) hypersomnias.

    PubMed

    Pizza, Fabio; Vandi, Stefano; Detto, Stefania; Poli, Francesca; Franceschini, Christian; Montagna, Pasquale; Plazzi, Giuseppe

    2011-03-01

    Excessive daytime sleepiness (EDS) has different correlates in non-rapid eye movement (NREM) [idiopathic hypersomnia (IH) without long sleep time] and REM sleep [narcolepsy without cataplexy (NwoC) and narcolepsy with cataplexy (NC)]-related hypersomnias of central origin. We analysed sleep onset characteristics at the multiple sleep latency test (MSLT) applying simultaneously two sleep onset criteria in 44 NC, seven NwoC and 16 IH consecutive patients referred for subjective EDS complaint. Sleep latency (SL) at MSLT was assessed both as the time elapsed to the occurrence of a single epoch of sleep Stage 1 NREM (SL) and of unequivocal sleep [three sleep Stage 1 NREM epochs or any other sleep stage epoch, sustained SL (SusSL)]. Idiopathic hypersomnia patients showed significantly (P<0.0001) longer SusSL than SL (7.7±2.5 versus 5.6±1.3 min, respectively) compared to NwoC (5.8±2.5 versus 5.3±2.2 min) and NC patients (4.1±3 versus 3.9±3 min). A mean difference threshold between SusSL and SL ≥27 s reached a diagnostic value to discriminate IH versus NC and NwoC sufferers (sensitivity 88%; specificity 82%). Moreover, NC patients showed better subjective sleepiness perception than NwoC and IH cases in the comparison between naps with or without sleep occurrence. Simultaneous application of the two widely used sleep onset criteria differentiates IH further from NC and NwoC patients: IH fluctuate through a wake-Stage 1 NREM sleep state before the onset of sustained sleep, while NC and NwoC shift abruptly into a sustained sleep. The combination of SusSL and SL determination at MSLT should be tested as an additional objective differential criterion for EDS disorders.

  3. In vivo nanoparticle imaging of innate immune cells can serve as a marker of disease severity in a model of multiple sclerosis

    PubMed Central

    Kirschbaum, Klara; Sonner, Jana K.; Zeller, Matthias W.; Deumelandt, Katrin; Bode, Julia; Sharma, Rakesh; Krüwel, Thomas; Fischer, Manuel; Hoffmann, Angelika; Costa da Silva, Milene; Muckenthaler, Martina U.; Wick, Wolfgang; Tews, Björn; Chen, John W.; Heiland, Sabine; Bendszus, Martin; Platten, Michael; Breckwoldt, Michael O.

    2016-01-01

    Innate immune cells play a key role in the pathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). Current clinical imaging is restricted to visualizing secondary effects of inflammation, such as gliosis and blood–brain barrier disruption. Advanced molecular imaging, such as iron oxide nanoparticle imaging, can allow direct imaging of cellular and molecular activity, but the exact cell types that phagocytose nanoparticles in vivo and how phagocytic activity relates to disease severity is not well understood. In this study we used MRI to map inflammatory infiltrates using high-field MRI and fluorescently labeled cross-linked iron oxide nanoparticles for cell tracking. We confirmed nanoparticle uptake and MR detectability ex vivo. Using in vivo MRI, we identified extensive nanoparticle signal in the cerebellar white matter and circumscribed cortical gray matter lesions that developed during the disease course (4.6-fold increase of nanoparticle accumulation in EAE compared with healthy controls, P < 0.001). Nanoparticles showed good cellular specificity for innate immune cells in vivo, labeling activated microglia, infiltrating macrophages, and neutrophils, whereas there was only sparse uptake by adaptive immune cells. Importantly, nanoparticle signal correlated better with clinical disease than conventional gadolinium (Gd) imaging (r, 0.83 for nanoparticles vs. 0.71 for Gd-imaging, P < 0.001). We validated our approach using the Food and Drug Administration-approved iron oxide nanoparticle ferumoxytol. Our results show that noninvasive molecular imaging of innate immune responses can serve as an imaging biomarker of disease activity in autoimmune-mediated neuroinflammation with potential clinical applications in a wide range of inflammatory diseases. PMID:27799546

  4. Circulating plasma cells in newly diagnosed symptomatic multiple myeloma as a possible prognostic marker for patients with standard-risk cytogenetics.

    PubMed

    Vagnoni, Davide; Travaglini, Fosco; Pezzoni, Valerio; Ruggieri, Miriana; Bigazzi, Catia; Dalsass, Alessia; Mestichelli, Francesca; Troiani, Emanuela; Falcioni, Sadia; Mazzotta, Serena; Natale, Annalisa; Angelini, Mario; Ferretti, Silvia; Angelini, Stefano; Galieni, Piero

    2015-08-01

    Detection of circulating plasma cells (PCs) in multiple myeloma (MM) patients is a well-known prognostic factor. We evaluated circulating PCs by flow cytometry (FC) in 104 patients with active MM at diagnosis by gating on CD38(+)  CD45(-) cells and examined their relationship with cytogenetic risk. Patients had an average follow-up of 36 months. By using a receiver operating characteristics analysis, we estimated the optimal cut-off of circulating PCs for defining poor prognosis to be 41. Patients with high-risk cytogenetics (n = 24) had poor prognosis, independently of circulating PC levels [PC < 41 vs. PC ≥ 41: overall survival (OS) = 0% vs. OS = 17%, P = not significant (n.s.); progression-free survival (PFS) = 0% vs. 17%, P = n.s.]. Patients with standard-risk cytogenetics (n = 65) showed a better prognosis when associated with a lower number of circulating PCs (PC < 41 vs. PC ≥ 41: OS = 62% vs. 24%, P = 0·008; PFS = 48% vs. 21%, P = 0·001). Multivariate analysis on the subgroup with standard-risk cytogenetics confirmed that the co-presence of circulating PCs ≥ 41, older age, Durie-Salmon stage >I and lack of maintenance adversely affected PFS, while OS was adversely affected only by lactate dehydrogenase, older age and lack of maintenance. Our results indicate that the quantification of circulating PCs by a simple two-colour FC analysis can provide useful prognostic information in newly diagnosed MM patients with standard-risk cytogenetics.

  5. High-intensity resistance training in multiple sclerosis - An exploratory study of effects on immune markers in blood and cerebrospinal fluid, and on mood, fatigue, health-related quality of life, muscle strength, walking and cognition.

    PubMed

    Kierkegaard, Marie; Lundberg, Ingrid E; Olsson, Tomas; Johansson, Sverker; Ygberg, Sofia; Opava, Christina; Holmqvist, Lotta Widén; Piehl, Fredrik

    2016-03-15

    High-intensity resistance training is unexplored in people with multiple sclerosis. To evaluate effects of high-intensity resistance training on immune markers and on measures of mood, fatigue, health-related quality of life, muscle strength, walking and cognition. Further, to describe participants' opinion and perceived changes of the training. Twenty patients with relapsing-remitting multiple sclerosis performed high-intensity resistance training at an intensity of 80% of one-repetition maximum, twice a week for 12 weeks. Blood and optional cerebrospinal fluid samples, and data on secondary outcome measures were collected before and after intervention. A study-specific questionnaire was used for capturing participants' opinion. Seventeen participants completed the study. Plasma cytokine levels of tumor necrosis factor were significantly decreased post-intervention (p=0.001). Exploratory cytokine analyses in cerebrospinal fluid (n=8) did not reveal major changes. Significant and clinically important improvements were found in fatigue (p=0.001) and health-related quality of life (p=0.004). Measures of mood (p=0.002), muscle strength (p ≤ 0.001), walking speed (p=0.013) and cognition (p=0.04) were also improved. A majority of participants evaluated the training as very good and perceived changes to the better. High-intensity resistance training in persons with relapsing remitting multiple sclerosis with low disability had positive effects on peripheral pro-inflammatory cytokine levels, led to clinically relevant improvements in measures of fatigue and health-related quality of life, and was well tolerated. These results provide a basis for a larger randomized trial. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. IKZF1 expression is a prognostic marker in newly diagnosed standard-risk multiple myeloma treated with lenalidomide and intensive chemotherapy: a study of the German Myeloma Study Group (DSMM).

    PubMed

    Krönke, J; Kuchenbauer, F; Kull, M; Teleanu, V; Bullinger, L; Bunjes, D; Greiner, A; Kolmus, S; Köpff, S; Schreder, M; Mügge, L-O; Straka, C; Engelhardt, M; Döhner, H; Einsele, H; Bassermann, F; Bargou, R; Knop, S; Langer, C

    2017-01-20

    Lenalidomide is an immunomodulatory compound with high clinical activity in multiple myeloma. Lenalidomide binding to the Cereblon (CRBN) E3 ubiquitin ligase results in targeted ubiquitination and degradation of the lymphoid transcription factors Ikaros (IKZF1) and Aiolos (IKZF3) leading to growth inhibition of multiple myeloma cells. Recently, Basigin (BSG) was identified as another protein regulated by CRBN that is involved in the activity of lenalidomide. Here, we analyzed the prognostic value of IKZF1, IKZF3, CRBN and BSG mRNA expression levels in pretreatment plasma cells from 60 patients with newly diagnosed multiple myeloma uniformly treated with lenalidomide in combination with intensive chemotherapy within a clinical trial. We found that IKZF1 mRNA expression levels are significantly associated with progression-free survival (PFS). Patients in the lowest quartile (Q1) of IKZF1 expression had a superior PFS compared with patients in the remaining quartiles (Q2-Q4; 3-year PFS of 86 vs 51%, P=0.01). This translated into a significant better overall survival (100 vs 74%, P=0.03). Subgroup analysis revealed a significant impact of IKZF1, IKZF3 and BSG expression levels on PFS in cytogenetically defined standard-risk but not high-risk patients. Our data suggest a prognostic role of IKZF1, IKZF3 and BSG expression levels in lenalidomide-treated multiple myeloma.Leukemia advance online publication, 20 January 2017; doi:10.1038/leu.2016.384.

  7. Tumor Markers

    MedlinePlus

    ... diagnosis and to assess response to treatment Nuclear matrix protein 22 Cancer type: Bladder cancer Tissue analyzed: ... are turning to proteomics (the study of protein structure, function, and patterns of expression) in hopes of ...

  8. Evaluating Markers for Guiding Treatment.

    PubMed

    Baker, Stuart G; Bonetti, Marco

    2016-09-01

    The subpopulation treatment effect pattern plot (STEPP) is an appealing method for assessing the clinical impact of a predictive marker on patient outcomes and identifying a promising subgroup for further study. However, its original formulation lacked a decision analytic justification and applied only to a single marker. We derive a decision-analytic result that motivates STEPP. We discuss the incorporation of multiple predictive markers into STEPP using risk difference, cadit, and responders-only benefit functions. Applying STEPP to data from a breast cancer treatment trial with multiple markers, we found that none of the three benefit functions identified a promising subgroup for further study. Applying STEPP to hypothetical data from a trial with 100 markers, we found that all three benefit functions identified promising subgroups as evidenced by the large statistically significant treatment effect in these subgroups. Because the method has desirable decision-analytic properties and yields an informative plot, it is worth applying to randomized trials on the chance there is a large treatment effect in a subgroup determined by the predictive markers. Published by Oxford University Press 2016. This work is written by US Government employees and is in the public domain in the United States.

  9. Climate Model Diagnostic Analyzer

    NASA Technical Reports Server (NTRS)

    Lee, Seungwon; Pan, Lei; Zhai, Chengxing; Tang, Benyang; Kubar, Terry; Zhang, Zia; Wang, Wei

    2015-01-01

    The comprehensive and innovative evaluation of climate models with newly available global observations is critically needed for the improvement of climate model current-state representation and future-state predictability. A climate model diagnostic evaluation process requires physics-based multi-variable analyses that typically involve large-volume and heterogeneous datasets, making them both computation- and data-intensive. With an exploratory nature of climate data analyses and an explosive growth of datasets and service tools, scientists are struggling to keep track of their datasets, tools, and execution/study history, let alone sharing them with others. In response, we have developed a cloud-enabled, provenance-supported, web-service system called Climate Model Diagnostic Analyzer (CMDA). CMDA enables the physics-based, multivariable model performance evaluations and diagnoses through the comprehensive and synergistic use of multiple observational data, reanalysis data, and model outputs. At the same time, CMDA provides a crowd-sourcing space where scientists can organize their work efficiently and share their work with others. CMDA is empowered by many current state-of-the-art software packages in web service, provenance, and semantic search.

  10. Downhole Fluid Analyzer Development

    SciTech Connect

    Bill Turner

    2006-11-28

    A novel fiber optic downhole fluid analyzer has been developed for operation in production wells. This device will allow real-time determination of the oil, gas and water fractions of fluids from different zones in a multizone or multilateral completion environment. The device uses near infrared spectroscopy and induced fluorescence measurement to unambiguously determine the oil, water and gas concentrations at all but the highest water cuts. The only downhole components of the system are the fiber optic cable and windows. All of the active components--light sources, sensors, detection electronics and software--will be located at the surface, and will be able to operate multiple downhole probes. Laboratory testing has demonstrated that the sensor can accurately determine oil, water and gas fractions with a less than 5 percent standard error. Once installed in an intelligent completion, this sensor will give the operating company timely information about the fluids arising from various zones or multilaterals in a complex completion pattern, allowing informed decisions to be made on controlling production. The research and development tasks are discussed along with a market analysis.

  11. Evaluation of practical schemes for correcting multiple scattering effects on gap fraction measurements by plant canopy analyzer LAI-2000/2200: implications for hemispherical photography and terrestrial laser scanners

    NASA Astrophysics Data System (ADS)

    Pisek, J.; Kobayashi, H.; Kuusk, A.

    2016-12-01

    Correct estimates of gap fraction are essential for quantifying canopy architectural variables, such as leaf area and clumping indices, which modify land-atmosphere interactions. The plant canopy analyzer (PCA) LAI-2000/2200 has been in use for the non-destructive determination of leaf area index (LAI), and other structural attributes of vegetative canopies for over 25 years (Li-Cor, 1989). The instrument is considered the world standard for indirect LAI measurements (Li-Cor, 2014). The PCA uses the gap fraction technique for calculation of LAI and mean inclination angle of foliage. However, gap fraction measurements from optical sensors are contaminated by radiation that is scattered by plant elements and ground surfaces. Three proposed alternative schemes for correcting multiple scattering effects on gap fraction measurements by PCA are evaluated: 1) Leblanc and Chen, 2001. Agric. For. Meteorol. 110, 125-139; 2) Kobayashi et al.., 2013. Agric. For. Meteorol. 174-175, 170-183; and 3) Kuusk, 2016. Agric. For. Meteorol. 221, 242-247. Collectively these methods provide suggestions for the correction of LAI estimates from measurements under wide range of illumination conditions. The PCA measurements were taken at two different RAMI (RAdiation transfer Model Intercomparison) stands in Järvselja, Estonia. All three schemes agreed reasonably well in the sparse and homogeneous RAMI Scots pine stand; the effective LAI would be underestimated by up to 13% if the corrections are not implemented. The proposed corrections varied from 7% (method by Kobayashi et al., 2013) up to 23% (method by Leblanc and Chen, 2001) in denser and heterogeneous RAMI birch stand. The role of scattered sky radiation in the estimation of gap fraction in vegetation canopies using passive optical techniques should be clearly accounted for even in case of perfectly overcast sky. The PCA measurements are considered a reference in developing methods of the estimation of gap fraction from hemispherical

  12. Marker evaluation of human breast and bladder cancers

    SciTech Connect

    Mayall, B.H.; Carroll, P.R.; Chen, Ling-Chun; Cohen, M.B.; Goodson, W.H. III; Smith, H.S.; Waldman, F.M. )

    1990-11-02

    We are investigating multiple markers in human breast and bladder cancers. Our aim is to identify markers that are clinically relevant and that contribute to our understanding of the disease process in individual patients. Good markers accurately assess the malignant potential of a cancer in an individual patient. Thus, they help identify those cancers that will recur, and they may be used to predict more accurately time to recurrence, response to treatment, and overall prognosis. Therapy and patient management may then be optimized to the individual patient. Relevant markers reflect the underlying pathobiology of individual tumors. As a tissue undergoes transformation from benign to malignant, the cells lose their differentiated phenotype. As a generalization, the more the cellular phenotype, cellular proliferation and cellular genotype depart from normal, the more advanced is the tumor in its biological evolution and the more likely it is that the patient has a poor prognosis. We use three studies to illustrate our investigation of potential tumor markers. Breast cancers are labeled in vivo with 5-bromodeoxyuridine (BrdUrd) to give a direct measure of the tumor labeling index. Bladder cancers are analyzed immunocytochemically using an antibody against proliferation. Finally, the techniques of molecular genetics are used to detect allelic loss in breast cancers. 6 refs., 3 figs.

  13. Association of Agronomic Traits with SNP Markers in Durum Wheat (Triticum turgidum L. durum (Desf.)).

    PubMed

    Hu, Xin; Ren, Jing; Ren, Xifeng; Huang, Sisi; Sabiel, Salih A I; Luo, Mingcheng; Nevo, Eviatar; Fu, Chunjie; Peng, Junhua; Sun, Dongfa

    2015-01-01

    Association mapping is a powerful approach to detect associations between traits of interest and genetic markers based on linkage disequilibrium (LD) in molecular plant breeding. In this study, 150 accessions of worldwide originated durum wheat germplasm (Triticum turgidum spp. durum) were genotyped using 1,366 SNP markers. The extent of LD on each chromosome was evaluated. Association of single nucleotide polymorphisms (SNP) markers with ten agronomic traits measured in four consecutive years was analyzed under a mix linear model (MLM). Two hundred and one significant association pairs were detected in the four years. Several markers were associated with one trait, and also some markers were associated with multiple traits. Some of the associated markers were in agreement with previous quantitative trait loci (QTL) analyses. The function and homology analyses of the corresponding ESTs of some SNP markers could explain many of the associations for plant height, length of main spike, number of spikelets on main spike, grain number per plant, and 1000-grain weight, etc. The SNP associations for the observed traits are generally clustered in specific chromosome regions of the wheat genome, mainly in 2A, 5A, 6A, 7A, 1B, and 6B chromosomes. This study demonstrates that association mapping can complement and enhance previous QTL analyses and provide additional information for marker-assisted selection.

  14. Association of Agronomic Traits with SNP Markers in Durum Wheat (Triticum turgidum L. durum (Desf.))

    PubMed Central

    Hu, Xin; Ren, Jing; Ren, Xifeng; Huang, Sisi; Sabiel, Salih A. I.; Luo, Mingcheng; Nevo, Eviatar; Fu, Chunjie; Peng, Junhua; Sun, Dongfa

    2015-01-01

    Association mapping is a powerful approach to detect associations between traits of interest and genetic markers based on linkage disequilibrium (LD) in molecular plant breeding. In this study, 150 accessions of worldwide originated durum wheat germplasm (Triticum turgidum spp. durum) were genotyped using 1,366 SNP markers. The extent of LD on each chromosome was evaluated. Association of single nucleotide polymorphisms (SNP) markers with ten agronomic traits measured in four consecutive years was analyzed under a mix linear model (MLM). Two hundred and one significant association pairs were detected in the four years. Several markers were associated with one trait, and also some markers were associated with multiple traits. Some of the associated markers were in agreement with previous quantitative trait loci (QTL) analyses. The function and homology analyses of the corresponding ESTs of some SNP markers could explain many of the associations for plant height, length of main spike, number of spikelets on main spike, grain number per plant, and 1000-grain weight, etc. The SNP associations for the observed traits are generally clustered in specific chromosome regions of the wheat genome, mainly in 2A, 5A, 6A, 7A, 1B, and 6B chromosomes. This study demonstrates that association mapping can complement and enhance previous QTL analyses and provide additional information for marker-assisted selection. PMID:26110423

  15. Blood Gas Analyzers.

    PubMed

    Gonzalez, Anthony L; Waddell, Lori S

    2016-03-01

    Acid-base and respiratory disturbances are common in sick and hospitalized veterinary patients; therefore, blood gas analyzers have become integral diagnostic and monitoring tools. This article will discuss uses of blood gas analyzers, types of samples that can be used, sample collection methods, potential sources of error, and potential alternatives to blood gas analyzers and their limitations. It will also discuss the types of analyzers that are available, logistical considerations that should be taken into account when purchasing an analyzer, and the basic principles of how these analyzers work. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Crew Activity Analyzer

    NASA Technical Reports Server (NTRS)

    Murray, James; Kirillov, Alexander

    2008-01-01

    The crew activity analyzer (CAA) is a system of electronic hardware and software for automatically identifying patterns of group activity among crew members working together in an office, cockpit, workshop, laboratory, or other enclosed space. The CAA synchronously records multiple streams of data from digital video cameras, wireless microphones, and position sensors, then plays back and processes the data to identify activity patterns specified by human analysts. The processing greatly reduces the amount of time that the analysts must spend in examining large amounts of data, enabling the analysts to concentrate on subsets of data that represent activities of interest. The CAA has potential for use in a variety of governmental and commercial applications, including planning for crews for future long space flights, designing facilities wherein humans must work in proximity for long times, improving crew training and measuring crew performance in military settings, human-factors and safety assessment, development of team procedures, and behavioral and ethnographic research. The data-acquisition hardware of the CAA (see figure) includes two video cameras: an overhead one aimed upward at a paraboloidal mirror on the ceiling and one mounted on a wall aimed in a downward slant toward the crew area. As many as four wireless microphones can be worn by crew members. The audio signals received from the microphones are digitized, then compressed in preparation for storage. Approximate locations of as many as four crew members are measured by use of a Cricket indoor location system. [The Cricket indoor location system includes ultrasonic/radio beacon and listener units. A Cricket beacon (in this case, worn by a crew member) simultaneously transmits a pulse of ultrasound and a radio signal that contains identifying information. Each Cricket listener unit measures the difference between the times of reception of the ultrasound and radio signals from an identified beacon

  17. WIPP marker development

    SciTech Connect

    1994-04-01

    This article discusses the development of permanent, passive markers for the Waste Isolation Pilot Plant (WIPP) and presents some preliminary concepts in drawings and a table of components for the markers. The panel, convened by Sandia National Laboratories, was charged with developing design characteristics for permanent markers and judging the efficacy of markers in deterring inadvertent human intrusion. 6 figs., 2 tabs.

  18. Multiple homicides.

    PubMed

    Copeland, A R

    1989-09-01

    A study of multiple homicides or multiple deaths involving a solitary incident of violence by another individual was performed on the case files of the Office of the Medical Examiner of Metropolitan Dade County in Miami, Florida, during 1983-1987. A total of 107 multiple homicides were studied: 88 double, 17 triple, one quadruple, and one quintuple. The 236 victims were analyzed regarding age, race, sex, cause of death, toxicologic data, perpetrator, locale of the incident, and reason for the incident. This article compares this type of slaying with other types of homicide including those perpetrated by serial killers. Suggestions for future research in this field are offered.

  19. [Genomic markers and anticancer chemotherapy].

    PubMed

    Nishiyama, Masahiko

    2008-02-01

    Worldwide research on the human genome exerts a major impact on medical science. The growing evidence that genetic polymorphisms in the metabolism, the disposition, and the targets of drugs can have an even greater influence on the efficacy and the toxicity led to the creation of a novel chemotherapeutic strategy, personalized medicine. Much effort has been directed toward identifying the indicators of individual response to drugs, and these studies have provided a variety of potent predictive markers of individual drug response, which include some significant markers in clinical practice with sufficient evidence. Personalized medicine based on the response prediction using genomic marker is increasingly being recognized as a practical treatment approach in cancer chemotherapy, and to be indispensable when molecular targeted drugs are involved in the therapy. Even so, the ingenious and intricate mechanism of individual drug response creates obstacles in predicting chemotherapeutic response: Multiple factors are involved in the mechanisms, and key factors for drug response vary significantly among individuals. DNA chip technology enables us to overview a huge number of gene expressions simultaneously, but gene expression profiles of drug sensitivity vary considerably even for the same drug, which shows the limited value of a static microarray-expression profile as a marker aimed at individualizing patient therapy. Selection of a set of truly significant genomic markers and understanding of their interplay are of key importance in prediction of individual response to drug therapies. Challenges to such biological complexity are now started to identify a better genomic marker. The contribution of genomic marker research to anticancer chemotherapy and problems of the day were reviewed.

  20. Analyzing Peace Pedagogies

    ERIC Educational Resources Information Center

    Haavelsrud, Magnus; Stenberg, Oddbjorn

    2012-01-01

    Eleven articles on peace education published in the first volume of the Journal of Peace Education are analyzed. This selection comprises peace education programs that have been planned or carried out in different contexts. In analyzing peace pedagogies as proposed in the 11 contributions, we have chosen network analysis as our method--enabling…

  1. Portable automatic blood analyzer

    NASA Technical Reports Server (NTRS)

    Coleman, R. L.

    1975-01-01

    Analyzer employs chemical-sensing electrodes for determination of blood, gas, and ion concentrations. It is rugged, easily serviced, and comparatively simple to operate. System can analyze up to eight parameters and can be modified to measure other blood constituents including nonionic species, such as urea, glucose, and oxygen.

  2. Analyzing Peace Pedagogies

    ERIC Educational Resources Information Center

    Haavelsrud, Magnus; Stenberg, Oddbjorn

    2012-01-01

    Eleven articles on peace education published in the first volume of the Journal of Peace Education are analyzed. This selection comprises peace education programs that have been planned or carried out in different contexts. In analyzing peace pedagogies as proposed in the 11 contributions, we have chosen network analysis as our method--enabling…

  3. Acoustical markers for CAD-detected pulmonary nodules in chest CT: A way to avoid suggestion and distraction of radiologist's attention?

    NASA Astrophysics Data System (ADS)

    Beyer, Florian; Heindel, Walter; Wormanns, Dag

    2009-02-01

    Purpose: To compare the influence of visual and acoustical CAD markers on radiologist's performance with regard to suggestive and distractive effects. Materials and methods: Ten radiologists analyzed 150 pictures of chest CT slices. Every picture contained a visual CAD marker. 100 pictures showed one nodule: CAD marker marked this in 50 cases and in 50 cases a false positive finding (f.p.). The other 50 cases showed no nodule but an f.p. marker. After 3 years same images were presented to thirteen radiologists with only a sound as CAD marker. 55 of 150 images were marked, 30 true positive and 25 f.p. Sensitivity and f.p. rate were calculated for both marker types. Significance between sensitivities and f.p. rates were calculated by multiple-analysis-of-variance (MANOVA). Results: Without CAD mean sensitivity resp. f.p. were 57.7% /.13. In case of correct optical resp. acoustical marker sensitivity increased to 75.6% resp. 63.1%. For incorrect set marker mean f.p. rate increased to .31 resp. .24. MANOVA showed that marker's correctness highly significantly influenced sensitivity (p<.001) and f.n. (p=.005). Type of marker showed no significant influence on sensitivity (p=.26) or f.n. (p=.23) but on f.p. (p<.001). New work to be presented: Acoustical markers are a new means to increase radiologist's awareness of the presence of pulmonary nodules at CT scans with much less suggestive effect compared to optical markers. Conclusion: We found an unexpectedly low distraction effect for misplaced CAD markers. A suggestive effect was remarkable especially for optical markers. However acoustical markers offered less increase of sensitivity.

  4. [The markers of wound vitality in forensic pathology].

    PubMed

    Gauchotte, Guillaume; Martrille, Laurent; Plénat, François; Vignaud, Jean-Michel

    2013-04-01

    Skin wounds datation is one of the most challenging problems in forensic pathology. The vitality of a recent wound cannot be affirmed when no inflammatory cell is visible. There are in the literature numerous studies about wound vitality, looking for markers involved in coagulation or inflammation, using various methods such as enzymology, molecular biology or immunohistochemistry. In this update, we first introduce some methodological principles to respect. Then, we review the main studies available in the literature. We insist on immunohistochemistry, which seems to be the more valuable method, given its easiness to perform and the possibility to analyze the localization of the molecules of interest. Some markers are promising, such as TNFα, IL-6, IL-1β, TGFα or TGFβ1. Before using them in daily practice, these first results need to be confirmed with other studies, driven by independent teams and integrating multiple controls. Most notably, the antibodies have to be tested in numerous post-mortem wounds. Indeed, there is a critical risk of overexpression in post-mortem wounds, and some interesting markers have been secondary invalidated because of post-mortem false positivity (e.g. fibronectin, P-selectin). Finally, optimal sensibility and specificity values would be probably reached by combining several markers, validated with large groups of pre- and post-mortem wounds.

  5. Marker Recycling in Candida albicans through CRISPR-Cas9-Induced Marker Excision

    PubMed Central

    2017-01-01

    ABSTRACT We describe here a new approach to marker recycling, a controlled sequence of steps in which a genetic marker is selected and then lost. Marker recycling is important for genetic manipulation, because it allows a single selection marker to be used repeatedly. Our approach relies upon the ability of the CRISPR-Cas9 system to make a targeted double-strand break in DNA and the expectation that a double-strand break within a selection marker may promote recombination between directly repeated sequences that flank the marker. We call the approach CRISPR-Cas9-induced marker excision (CRIME). We tested the utility of this approach with the fungal pathogen Candida albicans, which is typically diploid. We used two selection markers, modified to include flanking direct repeats. In a proof-of-principle study, we created successive homozygous deletions in three genes through use of the two markers and had one of the markers available in the final strain for further selection and recycling. This strategy will accelerate the creation of multiple-mutant strains in C. albicans. CRISPR-Cas9 systems have been applied to many organisms, so the genetic design principles described here may be broadly applicable. IMPORTANCE It is critical to be able to alter genes in order to elucidate their functions. These alterations often rely upon markers that allow selection for a rare cell in a population that has incorporated a piece of DNA. The number of alterations that can be accomplished is thus limited by the number of selection markers that are available. This limitation is circumvented by marker recycling strategies, in which a marker is eliminated after its initial use. Then, the marker can be used again. In this report, we describe a new marker recycling strategy that is enabled by recently developed CRISPR-Cas9 technology. PMID:28317025

  6. Microwave transient analyzer

    DOEpatents

    Gallegos, Cenobio H.; Ogle, James W.; Stokes, John L.

    1992-01-01

    A method and apparatus for capturing and recording indications of frequency content of electromagnetic signals and radiation is disclosed including a laser light source (12) and a Bragg cell (14) for deflecting a light beam (22) at a plurality of deflection angles (36) dependent upon frequency content of the signal. A streak camera (26) and a microchannel plate intensifier (28) are used to project Bragg cell (14) output onto either a photographic film (32) or a charge coupled device (CCD) imager (366). Timing markers are provided by a comb generator (50) and a one shot generator (52), the outputs of which are also routed through the streak camera (26) onto the film (32) or the CCD imager (366). Using the inventive method, the full range of the output of the Bragg cell (14) can be recorded as a function of time.

  7. Software Design Analyzer System

    NASA Technical Reports Server (NTRS)

    Tausworthe, R. C.

    1985-01-01

    CRISP80 software design analyzer system a set of programs that supports top-down, hierarchic, modular structured design, and programing methodologies. CRISP80 allows for expression of design as picture of program.

  8. Generating and Analyzing Data.

    ERIC Educational Resources Information Center

    Stevens, Jill

    1993-01-01

    Presents activities in which students develop and analyze scatterplots on graphing calculators to model corn growth, decay, a box of maximum volume, and weather prediction. Provides reproducible worksheets. (MDH)

  9. Generating and Analyzing Data.

    ERIC Educational Resources Information Center

    Stevens, Jill

    1993-01-01

    Presents activities in which students develop and analyze scatterplots on graphing calculators to model corn growth, decay, a box of maximum volume, and weather prediction. Provides reproducible worksheets. (MDH)

  10. Automatic amino acid analyzer

    NASA Technical Reports Server (NTRS)

    Berdahl, B. J.; Carle, G. C.; Oyama, V. I.

    1971-01-01

    Analyzer operates unattended or up to 15 hours. It has an automatic sample injection system and can be programmed. All fluid-flow valve switching is accomplished pneumatically from miniature three-way solenoid pilot valves.

  11. Analyzing Microarray Data.

    PubMed

    Hung, Jui-Hung; Weng, Zhiping

    2017-03-01

    Because there is no widely used software for analyzing RNA-seq data that has a graphical user interface, this protocol provides an example of analyzing microarray data using Babelomics. This analysis entails performing quantile normalization and then detecting differentially expressed genes associated with the transgenesis of a human oncogene c-Myc in mice. Finally, hierarchical clustering is performed on the differentially expressed genes using the Cluster program, and the results are visualized using TreeView.

  12. Soil Rock Analyzer

    NASA Technical Reports Server (NTRS)

    1985-01-01

    A redesigned version of a soil/rock analyzer developed by Martin Marietta under a Langley Research Center contract is being marketed by Aurora Tech, Inc. Known as the Aurora ATX-100, it has self-contained power, an oscilloscope, a liquid crystal readout, and a multichannel spectrum analyzer. It measures energy emissions to determine what elements in what percentages a sample contains. It is lightweight and may be used for mineral exploration, pollution monitoring, etc.

  13. Multiple epiphyseal dysplasia

    PubMed Central

    2009-01-01

    Background Multiple epiphyseal dysplasia (MED) is a common genetically and clinically heterogeneous skeletal dysplasia characterized by early-onset osteoarthritis, mainly in the hip and knee, and mild-to-moderate short stature. Here we report on a 6-generation MED family with 17 affected members. Method The clinical and radiographic data on the 12 affected members still living were scrutinized. A structured inquiry comprising state of health and MED-related symptoms since birth up to the present time and the osteoarthritis outcome (KOOS) questionnaire were sent to all living family members with MED. The 5 known gene loci for autosomal dominant MED were analyzed for linkage, using fluorescence-labeled microsatellite markers. Linkage was ascertained with markers close to the COL9A2 gene, which was analyzed for mutations by sequencing. Results We identified an exon 3 donor splice mutation in the COL9A2 gene in all affected family members. Clinical, radiographic, and questionnaire data from affected family members suggested that MED caused by COL9A2 mutations starts in early childhood with knee pain accompanied by delayed ossification of femoral epiphyses. The disease then either stabilizes during puberty or progresses with additional joints becoming affected; joint surgery might be necessary. The progression of the disease also affects muscles, with increasing atrophy, resulting in muscle fatigue and pain. Muscular atrophy has not been reported earlier in cases with COL9A2 mutations. Interpretation In a patient with clinically suspected or verified MED, it is important to perform DNA-based analysis to identify a possible disease-causing mutation. This information can be used to carry out genetic risk assessment of other family members and to achieve an early and correct diagnosis in the children. PMID:19995321

  14. CD30 antigen and multiple sclerosis: CD30, an important costimulatory molecule and marker of a regulatory subpopulation of dendritic cells, is involved in the maintenance of the physiological balance between TH1/TH2 immune responses and tolerance. The role of IFNbeta-1a in the treatment of multiple sclerosis.

    PubMed

    Pellegrini, Patrizia; Totaro, Rocco; Contasta, Ida; Berghella, Anna Maria; Carolei, Antonio; Adorno, Domenico

    2005-01-01

    The immunological effect of CD30 on dendritic cells (DCs) was examined in a comparative study of patients with relapsing-remitting multiple sclerosis (RRMS). The patients were divided into two groups on the basis of interferon (IFN)beta-1a treatment: IFNbeta-1a-treated patients and untreated patients. We have already shown that CD30 is a marker of cells involved in the regulation of the balance between TH1 and TH2 immune responses and so the aim of this study was to confirm this role in DCs and, consequently, to clarify the immunopathological mechanisms of MS and the causes of immunosuppressive drug failure. We studied network interactions between soluble (s) CD30 and TH1/TH2 cytokines in the supernatants of CD14+-derived immature DC (IDC) and DC cultures from treated and untreated patients. Network interactions between the sCD30 and cytokines in IDC and DC supernatants were also evaluated in relation to TH1/TH2 cytokine serum levels. Our overall results show that CD30 is expressed on IDCs and DCs, indicating an immunological role in resting and activated physiological conditions. This role would appear to be the regulation of the resting and activated physiological balance between the TH1/TH2 immune functions as abnormal increases in sCD30 levels result in impaired regulation. Further studies are undoubtedly required to clarify this situation. IFNbeta-1a treatment was found to determine a fall in sCD30 levels, leading to the restoration of the normal functional selection of IDCs from progenitor cells and the regulation of the TH1/TH2 network balance. However, IFNbeta-1a treatment may also be responsible for the in vivo suppression of CD30-mediated TH1-DC functions in immune activation. TH1-DC functions are involved in the induction of T-regulatory cells for the physiological deletion of self-aggressive cells. We conclude that CD30 is an important costimulatory molecule and marker of a regulatory subpopulation of DCs which induces and modulates immune cells

  15. Total organic carbon analyzer

    NASA Technical Reports Server (NTRS)

    Godec, Richard G.; Kosenka, Paul P.; Smith, Brian D.; Hutte, Richard S.; Webb, Johanna V.; Sauer, Richard L.

    1991-01-01

    The development and testing of a breadboard version of a highly sensitive total-organic-carbon (TOC) analyzer are reported. Attention is given to the system components including the CO2 sensor, oxidation reactor, acidification module, and the sample-inlet system. Research is reported for an experimental reagentless oxidation reactor, and good results are reported for linearity, sensitivity, and selectivity in the CO2 sensor. The TOC analyzer is developed with gravity-independent components and is designed for minimal additions of chemical reagents. The reagentless oxidation reactor is based on electrolysis and UV photolysis and is shown to be potentially useful. The stability of the breadboard instrument is shown to be good on a day-to-day basis, and the analyzer is capable of 5 sample analyses per day for a period of about 80 days. The instrument can provide accurate TOC and TIC measurements over a concentration range of 20 ppb to 50 ppm C.

  16. Electrosurgical unit analyzers.

    PubMed

    1998-07-01

    Electrosurgical unit (ESU) analyzers automate the testing and inspection of the output circuits and safety features of ESUs. They perform testing that would otherwise require several other pieces of equipment, as well as considerably more time and greater technician expertise. They are used largely by clinical engineering departments for routine inspection and preventive maintenance (IPM) procedures and, less often, for accident investigations and troubleshooting. In this Evaluation, we tested three ESU analyzers from three suppliers. We rated all three analyzers Acceptable and ranked them in two groupings. In ranking the units, we placed the greatest weight on ease of use for routine ESU inspections, and gave additional consideration to versatility for advanced applications such as ESU research. The unit in Group 1 was the easiest to use, especially for infrequent users. The units in Group 2 were satisfactory but require more frequent use to maintain proficiency and to avoid user errors.

  17. Total organic carbon analyzer

    NASA Technical Reports Server (NTRS)

    Godec, Richard G.; Kosenka, Paul P.; Smith, Brian D.; Hutte, Richard S.; Webb, Johanna V.; Sauer, Richard L.

    1991-01-01

    The development and testing of a breadboard version of a highly sensitive total-organic-carbon (TOC) analyzer are reported. Attention is given to the system components including the CO2 sensor, oxidation reactor, acidification module, and the sample-inlet system. Research is reported for an experimental reagentless oxidation reactor, and good results are reported for linearity, sensitivity, and selectivity in the CO2 sensor. The TOC analyzer is developed with gravity-independent components and is designed for minimal additions of chemical reagents. The reagentless oxidation reactor is based on electrolysis and UV photolysis and is shown to be potentially useful. The stability of the breadboard instrument is shown to be good on a day-to-day basis, and the analyzer is capable of 5 sample analyses per day for a period of about 80 days. The instrument can provide accurate TOC and TIC measurements over a concentration range of 20 ppb to 50 ppm C.

  18. Total organic carbon analyzer

    NASA Astrophysics Data System (ADS)

    Godec, Richard G.; Kosenka, Paul P.; Smith, Brian D.; Hutte, Richard S.; Webb, Johanna V.; Sauer, Richard L.

    The development and testing of a breadboard version of a highly sensitive total-organic-carbon (TOC) analyzer are reported. Attention is given to the system components including the CO2 sensor, oxidation reactor, acidification module, and the sample-inlet system. Research is reported for an experimental reagentless oxidation reactor, and good results are reported for linearity, sensitivity, and selectivity in the CO2 sensor. The TOC analyzer is developed with gravity-independent components and is designed for minimal additions of chemical reagents. The reagentless oxidation reactor is based on electrolysis and UV photolysis and is shown to be potentially useful. The stability of the breadboard instrument is shown to be good on a day-to-day basis, and the analyzer is capable of 5 sample analyses per day for a period of about 80 days. The instrument can provide accurate TOC and TIC measurements over a concentration range of 20 ppb to 50 ppm C.

  19. Advances in hematology analyzers.

    PubMed

    DeNicola, Dennis B

    2011-05-01

    The complete blood count is one of the basic building blocks of the minimum database in veterinary medicine. Over the past 20 years, there has been a tremendous advancement in the technology of hematology analyzers and their availability to the general practitioner. There are 4 basic methodologies that can be used to generate data for a complete blood count: manual methods, quantitative buffy coat analysis, automated impedance analysis, and flow cytometric analysis. This article will review the principles of these methodologies, discuss some of their advantages and disadvantages, and describe some of the hematology analyzers that are available for the in-house veterinary laboratory. Copyright © 2011. Published by Elsevier Inc.

  20. Ceramic subsurface marker prototypes

    SciTech Connect

    Lukens, C.E.

    1985-05-02

    The client submitted 5 sets of porcelain and stoneware subsurface (radioactive site) marker prototypes (31 markers each set). The following were determined: compressive strength, thermal shock resistance, thermal crazing resistance, alkali resistance, color retention, and chemical resistance.

  1. Analyzing Political Television Advertisements.

    ERIC Educational Resources Information Center

    Burson, George

    1992-01-01

    Presents a lesson plan to help students understand that political advertisements often mislead, lie, or appeal to emotion. Suggests that the lesson will enable students to examine political advertisements analytically. Includes a worksheet to be used by students to analyze individual political advertisements. (DK)

  2. Electronic sleep analyzer

    NASA Technical Reports Server (NTRS)

    Frost, J. D., Jr.

    1970-01-01

    Electronic instrument automatically monitors the stages of sleep of a human subject. The analyzer provides a series of discrete voltage steps with each step corresponding to a clinical assessment of level of consciousness. It is based on the operation of an EEG and requires very little telemetry bandwidth or time.

  3. List mode multichannel analyzer

    DOEpatents

    Archer, Daniel E.; Luke, S. John; Mauger, G. Joseph; Riot, Vincent J.; Knapp, David A.

    2007-08-07

    A digital list mode multichannel analyzer (MCA) built around a programmable FPGA device for onboard data analysis and on-the-fly modification of system detection/operating parameters, and capable of collecting and processing data in very small time bins (<1 millisecond) when used in histogramming mode, or in list mode as a list mode MCA.

  4. Analyzing Bilingual Education Costs.

    ERIC Educational Resources Information Center

    Bernal, Joe J.

    This paper examines the particular problems involved in analyzing the costs of bilingual education and suggests that cost analysis of bilingual education requires a fundamentally different approach than that followed in other recent school finance studies. Focus of the discussion is the Intercultural Development Research Association's (IDRA)…

  5. Analyzing Workforce Education. Monograph.

    ERIC Educational Resources Information Center

    Texas Community & Technical Coll. Workforce Education Consortium.

    This monograph examines the issue of task analysis as used in workplace literacy programs, debating the need for it and how to perform it in a rapidly changing environment. Based on experiences of community colleges in Texas, the report analyzes ways that task analysis can be done and how to implement work force education programs more quickly.…

  6. Analyzing Faculty Workload

    ERIC Educational Resources Information Center

    Holliman, Juanita M.

    1977-01-01

    Describes a step-by-step method for analyzing faculty workload which the author notes can determine exactly how a faculty member's time is spent and whether the hours available for teaching equal the hours required for teaching. Suggested uses for the method are noted, e.g., organizing the total work force based on desired curriculum changes. (SH)

  7. Analyzing Stereotypes in Media.

    ERIC Educational Resources Information Center

    Baker, Jackie

    1996-01-01

    A high school film teacher studied how students recognized messages in film, examining how film education could help students identify and analyze racial and gender stereotypes. Comparison of students' attitudes before and after the film course found that the course was successful in raising students' consciousness. (SM)

  8. Micro acoustic spectrum analyzer

    DOEpatents

    Schubert, W. Kent; Butler, Michael A.; Adkins, Douglas R.; Anderson, Larry F.

    2004-11-23

    A micro acoustic spectrum analyzer for determining the frequency components of a fluctuating sound signal comprises a microphone to pick up the fluctuating sound signal and produce an alternating current electrical signal; at least one microfabricated resonator, each resonator having a different resonant frequency, that vibrate in response to the alternating current electrical signal; and at least one detector to detect the vibration of the microfabricated resonators. The micro acoustic spectrum analyzer can further comprise a mixer to mix a reference signal with the alternating current electrical signal from the microphone to shift the frequency spectrum to a frequency range that is a better matched to the resonant frequencies of the microfabricated resonators. The micro acoustic spectrum analyzer can be designed specifically for portability, size, cost, accuracy, speed, power requirements, and use in a harsh environment. The micro acoustic spectrum analyzer is particularly suited for applications where size, accessibility, and power requirements are limited, such as the monitoring of industrial equipment and processes, detection of security intrusions, or evaluation of military threats.

  9. Analyzing HVAC piping systems

    SciTech Connect

    Smith, W.W. )

    1993-10-01

    This article describes requirements and considerations for a software tool for analyzing both the hydraulic and heat transfer characteristics of a HVAC system to help in selecting systems components and predicting their performance. The topics of the article include analysis of installed system evolution, selection and analysis of pumps and valves, heat transfer in heating and cooling coils, and capacity to handle large systems.

  10. PULSE AMPLITUDE ANALYZER

    DOEpatents

    Greenblatt, M.H.

    1958-03-25

    This patent pertains to pulse amplitude analyzers for sorting and counting a serles of pulses, and specifically discloses an analyzer which ls simple in construction and presents the puise height distribution visually on an oscilloscope screen. According to the invention, the pulses are applied to the vertical deflection plates of an oscilloscope and trigger the horizontal sweep. Each pulse starts at the same point on the screen and has a maximum amplitude substantially along the same vertical line. A mask is placed over the screen except for a slot running along the line where the maximum amplitudes of the pulses appear. After the slot has been scanned by a photocell in combination with a slotted rotating disk, the photocell signal is displayed on an auxiliary oscilloscope as vertical deflection along a horizontal time base to portray the pulse amplitude distribution.

  11. Soft Decision Analyzer

    NASA Technical Reports Server (NTRS)

    Lansdowne, Chatwin; Steele, Glen; Zucha, Joan; Schlesinger, Adam

    2013-01-01

    We describe the benefit of using closed-loop measurements for a radio receiver paired with a counterpart transmitter. We show that real-time analysis of the soft decision output of a receiver can provide rich and relevant insight far beyond the traditional hard-decision bit error rate (BER) test statistic. We describe a Soft Decision Analyzer (SDA) implementation for closed-loop measurements on single- or dual- (orthogonal) channel serial data communication links. The analyzer has been used to identify, quantify, and prioritize contributors to implementation loss in live-time during the development of software defined radios. This test technique gains importance as modern receivers are providing soft decision symbol synchronization as radio links are challenged to push more data and more protocol overhead through noisier channels, and software-defined radios (SDRs) use error-correction codes that approach Shannon's theoretical limit of performance.

  12. Dissolved Hydrogen Analyzer

    DTIC Science & Technology

    2006-05-01

    chlorinated volatile organic compounds (VOC) at Bangor Naval Submarine Base in Kitsap County , Washington (SUBASE Bangor) • Chlorinated VOCs at...the DH analyzer was evaluated based on the following criteria: • Accuracy as demonstrated by a one-to-one correlation between the standard bubble...accurately measure gaseous hydrogen was negatively impacted by the presence of other gases that partitioned from groundwater during gas-liquid

  13. Magnetoresistive Emulsion Analyzer

    PubMed Central

    Lin, Gungun; Baraban, Larysa; Han, Luyang; Karnaushenko, Daniil; Makarov, Denys; Cuniberti, Gianaurelio; Schmidt, Oliver G.

    2013-01-01

    We realize a magnetoresistive emulsion analyzer capable of detection, multiparametric analysis and sorting of ferrofluid-containing nanoliter-droplets. The operation of the device in a cytometric mode provides high throughput and quantitative information about the dimensions and magnetic content of the emulsion. Our method offers important complementarity to conventional optical approaches involving ferrofluids, and paves the way to the development of novel compact tools for diagnostics and nanomedicine including drug design and screening. PMID:23989504

  14. PULSE AMPLITUDE ANALYZER

    DOEpatents

    Gray, G.W.; Jensen, A.S.

    1957-10-22

    A pulse-height analyzer system of improved design for sorting and counting a series of pulses, such as provided by a scintillation detector in nuclear radiation measurements, is described. The analyzer comprises a main transmission line, a cathode-ray tube for each section of the line with its deflection plates acting as the line capacitance; means to bias the respective cathode ray tubes so that the beam strikes a target only when a prearranged pulse amplitude is applied, with each tube progressively biased to respond to smaller amplitudes; pulse generating and counting means associated with each tube to respond when the beam is deflected; a control transmission line having the same time constant as the first line per section with pulse generating means for each tube for initiating a pulse on the second transmission line when a pulse triggers the tube of corresponding amplitude response, the former pulse acting to prevent successive tubes from responding to the pulse under test. This arrangement permits greater deflection sensitivity in the cathode ray tube and overcomes many of the disadvantages of prior art pulse-height analyzer circuits.

  15. Developing single nucleotide polymorphism (SNP) markers from transcriptome sequences for identification of longan (Dimocarpus longan) germplasm

    PubMed Central

    Wang, Boyi; Tan, Hua-Wei; Fang, Wanping; Meinhardt, Lyndel W; Mischke, Sue; Matsumoto, Tracie; Zhang, Dapeng

    2015-01-01

    Longan (Dimocarpus longan Lour.) is an important tropical fruit tree crop. Accurate varietal identification is essential for germplasm management and breeding. Using longan transcriptome sequences from public databases, we developed single nucleotide polymorphism (SNP) markers; validated 60 SNPs in 50 longan germplasm accessions, including cultivated varieties and wild germplasm; and designated 25 SNP markers that unambiguously identified all tested longan varieties with high statistical rigor (P<0.0001). Multiple trees from the same clone were verified and off-type trees were identified. Diversity analysis revealed genetic relationships among analyzed accessions. Cultivated varieties differed significantly from wild populations (Fst=0.300; P<0.001), demonstrating untapped genetic diversity for germplasm conservation and utilization. Within cultivated varieties, apparent differences between varieties from China and those from Thailand and Hawaii indicated geographic patterns of genetic differentiation. These SNP markers provide a powerful tool to manage longan genetic resources and breeding, with accurate and efficient genotype identification. PMID:26504559

  16. RELAPS desktop analyzer

    SciTech Connect

    Beelman, R.J.; Grush, W.H.; Mortensen, G.A.; Snider, D.M.; Wagner, K.L.

    1989-01-01

    The previously mainframe bound RELAP5 reactor safety computer code has been installed on a microcomputer. A simple color-graphic display driver has been developed to enable the user to view the code results as the calculation advances. In order to facilitate future interactive desktop applications, the Nuclear Plant Analyzer (NPA), also previously mainframe bound, is being redesigned to encompass workstation applications. The marriage of RELAP5 simulation capabilities with NPA interactive graphics on a desktop workstation promises to revolutionize reactor safety analysis methodology. 8 refs.

  17. Inductive dielectric analyzer

    NASA Astrophysics Data System (ADS)

    Agranovich, Daniel; Polygalov, Eugene; Popov, Ivan; Ben Ishai, Paul; Feldman, Yuri

    2017-03-01

    One of the approaches to bypass the problem of electrode polarization in dielectric measurements is the free electrode method. The advantage of this technique is that, the probing electric field in the material is not supplied by contact electrodes, but rather by electromagnetic induction. We have designed an inductive dielectric analyzer based on a sensor comprising two concentric toroidal coils. In this work, we present an analytic derivation of the relationship between the impedance measured by the sensor and the complex dielectric permittivity of the sample. The obtained relationship was successfully employed to measure the dielectric permittivity and conductivity of various alcohols and aqueous salt solutions.

  18. Mineral/Water Analyzer

    NASA Technical Reports Server (NTRS)

    1983-01-01

    An x-ray fluorescence spectrometer developed for the Viking Landers by Martin Marietta was modified for geological exploration, water quality monitoring, and aircraft engine maintenance. The aerospace system was highly miniaturized and used very little power. It irradiates the sample causing it to emit x-rays at various energies, then measures the energy levels for sample composition analysis. It was used in oceanographic applications and modified to identify element concentrations in ore samples, on site. The instrument can also analyze the chemical content of water, and detect the sudden development of excessive engine wear.

  19. Analyzing the "correct" endpoint.

    PubMed

    Atherton, Pamela J; Novotny, Paul J; Tan, Angelina D

    2006-01-01

    The choice of QOL endpoints for a study should be based on which score will most likely change if the treatment is favorable. How the QOL change is calculated should be based on the expected amount of missing data, how many time points data will be collected, and whether extreme outliers in the scores impact results. The study should have sufficient power to detect a meaningful difference between arms (typically 10 points on a 0-100 point scale) in the chosen QOL endpoint. At the conclusion of a study, several secondary endpoints can be analyzed which can provide additional information and confirm primary endpoint results.

  20. Fractional channel multichannel analyzer

    DOEpatents

    Brackenbush, Larry W.; Anderson, Gordon A.

    1994-01-01

    A multichannel analyzer incorporating the features of the present invention obtains the effect of fractional channels thus greatly reducing the number of actual channels necessary to record complex line spectra. This is accomplished by using an analog-to-digital converter in the asynscronous mode, i.e., the gate pulse from the pulse height-to-pulse width converter is not synchronized with the signal from a clock oscillator. This saves power and reduces the number of components required on the board to achieve the effect of radically expanding the number of channels without changing the circuit board.

  1. Fractional channel multichannel analyzer

    DOEpatents

    Brackenbush, L.W.; Anderson, G.A.

    1994-08-23

    A multichannel analyzer incorporating the features of the present invention obtains the effect of fractional channels thus greatly reducing the number of actual channels necessary to record complex line spectra. This is accomplished by using an analog-to-digital converter in the asynchronous mode, i.e., the gate pulse from the pulse height-to-pulse width converter is not synchronized with the signal from a clock oscillator. This saves power and reduces the number of components required on the board to achieve the effect of radically expanding the number of channels without changing the circuit board. 9 figs.

  2. Electrodynamic thermogravimetric analyzer

    NASA Astrophysics Data System (ADS)

    Spjut, R. Erik; Bar-Ziv, Ezra; Sarofim, Adel F.; Longwell, John P.

    1986-08-01

    The design and operation of a new device for studying single-aerosol-particle kinetics at elevated temperatures, the electrodynamic thermogravimetric analyzer (EDTGA), was examined theoretically and experimentally. The completed device consists of an electrodynamic balance modified to permit particle heating by a CO2 laser, temperature measurement by a three-color infrared-pyrometry system, and continuous weighing by a position-control system. In this paper, the position-control, particle-weight-measurement, heating, and temperature-measurement systems are described and their limitations examined.

  3. Portable Gas Analyzer

    NASA Technical Reports Server (NTRS)

    1986-01-01

    The Michromonitor M500 universal gas analyzer contains a series of miniature modules, each of which is a complete gas chromatograph, an instrument which separates a gaseous mixture into its components and measures the concentrations of each gas in the mixture. The system is manufactured by Microsensor Technology, and is used for environmental analysis, monitoring for gas leaks and chemical spills, compliance with pollution laws, etc. The technology is based on a Viking attempt to detect life on Mars. Ames/Stanford miniaturized the system and NIOSH funded further development. Three Stanford researchers commercialized the technology, which can be operated by unskilled personnel.

  4. Fluorescence analyzer for lignin

    DOEpatents

    Berthold, John W.; Malito, Michael L.; Jeffers, Larry

    1993-01-01

    A method and apparatus for measuring lignin concentration in a sample of wood pulp or black liquor comprises a light emitting arrangement for emitting an excitation light through optical fiber bundles into a probe which has an undiluted sensing end facing the sample. The excitation light causes the lignin concentration to produce fluorescent emission light which is then conveyed through the probe to analyzing equipment which measures the intensity of the emission light. Measures a This invention was made with Government support under Contract Number DOE: DE-FC05-90CE40905 awarded by the Department of Energy (DOE). The Government has certain rights in this invention.

  5. Field Deployable DNA analyzer

    SciTech Connect

    Wheeler, E; Christian, A; Marion, J; Sorensen, K; Arroyo, E; Vrankovich, G; Hara, C; Nguyen, C

    2005-02-09

    This report details the feasibility of a field deployable DNA analyzer. Steps for swabbing cells from surfaces and extracting DNA in an automatable way are presented. Since enzymatic amplification reactions are highly sensitive to environmental contamination, sample preparation is a crucial step to make an autonomous deployable instrument. We perform sample clean up and concentration in a flow through packed bed. For small initial samples, whole genome amplification is performed in the packed bed resulting in enough product for subsequent PCR amplification. In addition to DNA, which can be used to identify a subject, protein is also left behind, the analysis of which can be used to determine exposure to certain substances, such as radionuclides. Our preparative step for DNA analysis left behind the protein complement as a waste stream; we determined to learn if the proteins themselves could be analyzed in a fieldable device. We successfully developed a two-step lateral flow assay for protein analysis and demonstrate a proof of principle assay.

  6. Analyzing Aeroelasticity in Turbomachines

    NASA Technical Reports Server (NTRS)

    Reddy, T. S. R.; Srivastava, R.

    2003-01-01

    ASTROP2-LE is a computer program that predicts flutter and forced responses of blades, vanes, and other components of such turbomachines as fans, compressors, and turbines. ASTROP2-LE is based on the ASTROP2 program, developed previously for analysis of stability of turbomachinery components. In developing ASTROP2- LE, ASTROP2 was modified to include a capability for modeling forced responses. The program was also modified to add a capability for analysis of aeroelasticity with mistuning and unsteady aerodynamic solutions from another program, LINFLX2D, that solves the linearized Euler equations of unsteady two-dimensional flow. Using LINFLX2D to calculate unsteady aerodynamic loads, it is possible to analyze effects of transonic flow on flutter and forced response. ASTROP2-LE can be used to analyze subsonic, transonic, and supersonic aerodynamics and structural mistuning for rotors with blades of differing structural properties. It calculates the aerodynamic damping of a blade system operating in airflow so that stability can be assessed. The code also predicts the magnitudes and frequencies of the unsteady aerodynamic forces on the airfoils of a blade row from incoming wakes. This information can be used in high-cycle fatigue analysis to predict the fatigue lives of the blades.

  7. Plutonium solution analyzer

    SciTech Connect

    Burns, D.A.

    1994-09-01

    A fully automated analyzer has been developed for plutonium solutions. It was assembled from several commercially available modules, is based upon segmented flow analysis, and exhibits precision about an order of magnitude better than commercial units (0.5%-O.05% RSD). The system was designed to accept unmeasured, untreated liquid samples in the concentration range 40-240 g/L and produce a report with sample identification, sample concentrations, and an abundance of statistics. Optional hydraulics can accommodate samples in the concentration range 0.4-4.0 g/L. Operating at a typical rate of 30 to 40 samples per hour, it consumes only 0.074 mL of each sample and standard, and generates waste at the rate of about 1.5 mL per minute. No radioactive material passes through its multichannel peristaltic pump (which remains outside the glovebox, uncontaminated) but rather is handled by a 6-port, 2-position chromatography-type loop valve. An accompanying computer is programmed in QuickBASIC 4.5 to provide both instrument control and data reduction. The program is truly user-friendly and communication between operator and instrument is via computer screen displays and keyboard. Two important issues which have been addressed are waste minimization and operator safety (the analyzer can run in the absence of an operator, once its autosampler has been loaded).

  8. Analyzing the platelet proteome.

    PubMed

    García, Angel; Zitzmann, Nicole; Watson, Steve P

    2004-08-01

    During the last 10 years, mass spectrometry (MS) has become a key tool for protein analysis and has underpinned the emerging field of proteomics. Using high-throughput tandem MS/MS following protein separation, it is potentially possible to analyze hundreds to thousands of proteins in a sample at a time. This technology can be used to analyze the protein content (i.e., the proteome) of any cell or tissue and complements the powerful field of genomics. The technology is particularly suitable for platelets because of the absence of a nucleus. Cellular proteins can be separated by either gel-based methods such as two-dimensional gel electrophoresis or one-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis followed by liquid chromatography (LC) -MS/MS or by multidimensional LC-MS/MS. Prefractionation techniques, such as subcellular fractionations or immunoprecipitations, can be used to improve the analysis. Each method has particular advantages and disadvantages. Proteomics can be used to compare the proteome of basal and diseased platelets, helping to reveal information on the molecular basis of the disease.

  9. Ring Image Analyzer

    NASA Technical Reports Server (NTRS)

    Strekalov, Dmitry V.

    2012-01-01

    Ring Image Analyzer software analyzes images to recognize elliptical patterns. It determines the ellipse parameters (axes ratio, centroid coordinate, tilt angle). The program attempts to recognize elliptical fringes (e.g., Newton Rings) on a photograph and determine their centroid position, the short-to-long-axis ratio, and the angle of rotation of the long axis relative to the horizontal direction on the photograph. These capabilities are important in interferometric imaging and control of surfaces. In particular, this program has been developed and applied for determining the rim shape of precision-machined optical whispering gallery mode resonators. The program relies on a unique image recognition algorithm aimed at recognizing elliptical shapes, but can be easily adapted to other geometric shapes. It is robust against non-elliptical details of the image and against noise. Interferometric analysis of precision-machined surfaces remains an important technological instrument in hardware development and quality analysis. This software automates and increases the accuracy of this technique. The software has been developed for the needs of an R&TD-funded project and has become an important asset for the future research proposal to NASA as well as other agencies.

  10. Coaxial charged particle energy analyzer

    NASA Technical Reports Server (NTRS)

    Kelly, Michael A. (Inventor); Bryson, III, Charles E. (Inventor); Wu, Warren (Inventor)

    2011-01-01

    A non-dispersive electrostatic energy analyzer for electrons and other charged particles having a generally coaxial structure of a sequentially arranged sections of an electrostatic lens to focus the beam through an iris and preferably including an ellipsoidally shaped input grid for collimating a wide acceptance beam from a charged-particle source, an electrostatic high-pass filter including a planar exit grid, and an electrostatic low-pass filter. The low-pass filter is configured to reflect low-energy particles back towards a charged particle detector located within the low-pass filter. Each section comprises multiple tubular or conical electrodes arranged about the central axis. The voltages on the lens are scanned to place a selected energy band of the accepted beam at a selected energy at the iris. Voltages on the high-pass and low-pass filters remain substantially fixed during the scan.

  11. Alzheimer's disease: analyzing the missing heritability.

    PubMed

    Ridge, Perry G; Mukherjee, Shubhabrata; Crane, Paul K; Kauwe, John S K

    2013-01-01

    Alzheimer's disease (AD) is a complex disorder influenced by environmental and genetic factors. Recent work has identified 11 AD markers in 10 loci. We used Genome-wide Complex Trait Analysis to analyze >2 million SNPs for 10,922 individuals from the Alzheimer's Disease Genetics Consortium to assess the phenotypic variance explained first by known late-onset AD loci, and then by all SNPs in the Alzheimer's Disease Genetics Consortium dataset. In all, 33% of total phenotypic variance is explained by all common SNPs. APOE alone explained 6% and other known markers 2%, meaning more than 25% of phenotypic variance remains unexplained by known markers, but is tagged by common SNPs included on genotyping arrays or imputed with HapMap genotypes. Novel AD markers that explain large amounts of phenotypic variance are likely to be rare and unidentifiable using genome-wide association studies. Based on our findings and the current direction of human genetics research, we suggest specific study designs for future studies to identify the remaining heritability of Alzheimer's disease.

  12. Nano-Dust Analyzer

    NASA Astrophysics Data System (ADS)

    Gruen, E.; Horanyi, M.; Moebius, E.; Sternovsky, Z.; Auer, S.; Srama, R.; Juhasz, A.

    2010-12-01

    Recently, the STEREO WAVES instruments recorded a large number of intense electric field signals, which were interpreted as impacts from nanometer sized particles striking the spacecraft with velocities of about the solar wind speed [1]. This high flux and strong spatial and/or temporal variations of nanometer sized dust grains at low latitude appears to be uncorrelated with the solar wind properties. Early dust instruments onboard Pioneer 8 and 9 and Helios spacecraft detected a flow of submicron sized dust particles coming from the direction of the Sun. These particles originate in the inner solar system from mutual collisions among meteoroids and move on hyperbolic orbits that leave the Solar System under the prevailing radiation pressure force [2]. The observed fluxes of inner-source pickup ions also point to the existence of a much enhanced dust population in the nanometer size range [3]. A new highly sensitive instrument is being developed within NASA's Heliophysics Program to confirm the existence of the so-called nano-dust particles, characterize their impact parameters, and measure their chemical composition. The instrument is based on the Cassini Dust Analyzer (CDA) that has analyzed the composition of nanometer sized dust particles emanating from the Jovian and Saturnian systems but could not be pointed towards the Sun. By applying technologies implemented in solar wind instruments and coronagraphs a highly sensitive dust analyzer will be developed and tested in the laboratory. The measurements will enable us to identify the source of the dust by comparing their elemental composition with that of larger micrometeoroid particles of cometary and asteroid origin and will reveal interaction of nano-dust with the interplanetary medium by investigating the relation of the dust flux with solar wind and IMF properties. [1] Meyer-Vernet, N. et al., Solar Physics, 256, 463, 2009 [2] Zook, H.A. and Berg, O.E.: A source for hyperbolic cosmic dust particles

  13. UCNB_Analyzer

    SciTech Connect

    Broussard, Leah J

    2016-01-17

    The purpose of this software is to interpret and analyze data taken using the NI PXIe-5171R digitizer based data acquisition system for the UCNB and Nab experiments. The detection and data acquisition systems are identical for the 2 experiments, with some differences in analysis requirements. The software converts raw binary files produced by the NI DAQ into ROOT TTree format, performs waveform analysis using trapezoidal filter algorithms, pulse fitting, and noise analysis routines, and applies variable criteria to identify valid events in the data stream. The software will be used to perform analysis of the events for multi-channel coincidences, timing and energy studies, and event rates under different experimental conditions.

  14. Analyzing Water's Optical Absorption

    NASA Technical Reports Server (NTRS)

    2002-01-01

    A cooperative agreement between World Precision Instruments (WPI), Inc., and Stennis Space Center has led the UltraPath(TM) device, which provides a more efficient method for analyzing the optical absorption of water samples at sea. UltraPath is a unique, high-performance absorbance spectrophotometer with user-selectable light path lengths. It is an ideal tool for any study requiring precise and highly sensitive spectroscopic determination of analytes, either in the laboratory or the field. As a low-cost, rugged, and portable system capable of high- sensitivity measurements in widely divergent waters, UltraPath will help scientists examine the role that coastal ocean environments play in the global carbon cycle. UltraPath(TM) is a trademark of World Precision Instruments, Inc. LWCC(TM) is a trademark of World Precision Instruments, Inc.

  15. Analyzing Next to Nothing

    NASA Astrophysics Data System (ADS)

    Taylor, G. J.

    2000-04-01

    Analytical techniques have advanced so far that it is possible to slice up a sample only 10 micrometers across (with a mass of only a billionth of a gram) so that a dozen microanalytical techniques can be used to extract fascinating, crucial information about the sample's history. This astonishing ability is useful in analyzing interplanetary dust collected in the stratosphere, tiny interstellar grains in meteorites, sparse and wispy weathering products in Martian meteorites, and samples to be collected and returned to Earth by current and future sample return missions from comets, asteroids, Martian moons, and Mars. The importance of the array of techniques available to cosmochemists has been documented by Michael Zolensky (Johnson Space Center), Carle Pieters (Brown University), Benton Clark (Lockheed Martin Astronautics, Denver), and James Papike (University of New Mexico), with special attention to sample-return missions.

  16. Analyzing cosmic bubble collisions

    SciTech Connect

    Gobbetti, Roberto; Kleban, Matthew E-mail: mk161@nyu.edu

    2012-05-01

    We develop a set of controlled, analytic approximations to study the effects of bubble collisions on cosmology. We expand the initial perturbation to the inflaton field caused by the collision in a general power series, and determine its time evolution during inflation in terms of the coefficients in the expansion. In models where the observer's bubble undergoes sufficient slow-roll inflation to solve the flatness problem, in the thin wall limit only one coefficient in the expansion is relevant to observational cosmology, allowing nearly model-independent predictions. We discuss two approaches to determining the initial perturbation to the inflaton and the implications for the sign of the effect (a hot or cold spot on the Cosmic Microwave Background temperature map). Lastly, we analyze the effects of collisions with thick-wall bubbles, i.e. away from the thin-wall limit.

  17. Analyzing a Cometary 'Sneeze'

    NASA Technical Reports Server (NTRS)

    2005-01-01

    [figure removed for brevity, see original site] Figure 1: Analyzing a Cometary 'Sneeze'

    This display shows highly processed images of the outburst of comet Tempel 1 between June 22 and 23, 2005. The pictures were taken by Deep Impact's medium-resolution camera. An average image of the comet has been subtracted from each picture to provide an enhanced view of the outburst. The intensity has also been stretched to show the faintest parts. This processing enables measurement of the outflow speed and the details of the dissipation of the outburst. The left image was taken when the comet was very close to its normal, non-bursting state, so almost nothing is visible.

  18. Analyzing geographic clustered response

    SciTech Connect

    Merrill, D.W.; Selvin, S.; Mohr, M.S.

    1991-08-01

    In the study of geographic disease clusters, an alternative to traditional methods based on rates is to analyze case locations on a transformed map in which population density is everywhere equal. Although the analyst's task is thereby simplified, the specification of the density equalizing map projection (DEMP) itself is not simple and continues to be the subject of considerable research. Here a new DEMP algorithm is described, which avoids some of the difficulties of earlier approaches. The new algorithm (a) avoids illegal overlapping of transformed polygons; (b) finds the unique solution that minimizes map distortion; (c) provides constant magnification over each map polygon; (d) defines a continuous transformation over the entire map domain; (e) defines an inverse transformation; (f) can accept optional constraints such as fixed boundaries; and (g) can use commercially supported minimization software. Work is continuing to improve computing efficiency and improve the algorithm. 21 refs., 15 figs., 2 tabs.

  19. Residual gas analyzer calibration

    NASA Technical Reports Server (NTRS)

    Lilienkamp, R. H.

    1972-01-01

    A technique which employs known gas mixtures to calibrate the residual gas analyzer (RGA) is described. The mass spectra from the RGA are recorded for each gas mixture. This mass spectra data and the mixture composition data each form a matrix. From the two matrices the calibration matrix may be computed. The matrix mathematics requires the number of calibration gas mixtures be equal to or greater than the number of gases included in the calibration. This technique was evaluated using a mathematical model of an RGA to generate the mass spectra. This model included shot noise errors in the mass spectra. Errors in the gas concentrations were also included in the valuation. The effects of these errors was studied by varying their magnitudes and comparing the resulting calibrations. Several methods of evaluating an actual calibration are presented. The effects of the number of gases in then, the composition of the calibration mixture, and the number of mixtures used are discussed.

  20. Motion detector and analyzer

    DOEpatents

    Unruh, W.P.

    1987-03-23

    Method and apparatus are provided for deriving positive and negative Doppler spectrum to enable analysis of objects in motion, and particularly, objects having rotary motion. First and second returned radar signals are mixed with internal signals to obtain an in-phase process signal and a quadrature process signal. A broad-band phase shifter shifts the quadrature signal through 90/degree/ relative to the in-phase signal over a predetermined frequency range. A pair of signals is output from the broad-band phase shifter which are then combined to provide a first side band signal which is functionally related to a negative Doppler shift spectrum. The distinct positive and negative Doppler spectra may then be analyzed for the motion characteristics of the object being examined.

  1. Moving particle composition analyzer

    NASA Technical Reports Server (NTRS)

    Auer, S. O. (Inventor)

    1976-01-01

    A mass spectrometry apparatus for analyzing the composition of moving microscopic particles is introduced. The apparatus includes a capacitor with a front electrode upon which the particles impinge, a back electrode, and a solid dielectric sandwiched between the front and back electrodes. In one embodiment, the electrodes and dielectric are arcuately shaped as concentric peripheral segments of different spheres having a common center and different radii. The front electrode and dielectric together have a thickness such that an impinging particle can penetrate them. In a second embodiment, the capacitor has planar, parallel electrodes, in which case the ejected positive ions are deflected downstream of a planar grid by a pair of spaced, arcuate capacitor plates having a region between them through which the ejected ions travel.

  2. Analyzing Atmospheric Neutrino Oscillations

    SciTech Connect

    Escamilla, J.; Ernst, D. J.; Latimer, D. C.

    2007-10-26

    We provide a pedagogic derivation of the formula needed to analyze atmospheric data and then derive, for the subset of the data that are fully-contained events, an analysis tool that is quantitative and numerically efficient. Results for the full set of neutrino oscillation data are then presented. We find the following preliminary results: 1.) the sub-dominant approximation provides reasonable values for the best fit parameters for {delta}{sub 32}, {theta}{sub 23}, and {theta}{sub 13} but does not quantitatively provide the errors for these three parameters; 2.) the size of the MSW effect is suppressed in the sub-dominant approximation; 3.) the MSW effect reduces somewhat the extracted error for {delta}{sub 32}, more so for {theta}{sub 23} and {theta}{sub 13}; 4.) atmospheric data alone constrains the allowed values of {theta}{sub 13} only in the sub-dominant approximation, the full three neutrino calculations requires CHOOZ to get a clean constraint; 5.) the linear in {theta}{sub 13} terms are not negligible; and 6.) the minimum value of {theta}{sub 13} is found to be negative, but at a statistically insignificant level.

  3. Analyzing Spacecraft Telecommunication Systems

    NASA Technical Reports Server (NTRS)

    Kordon, Mark; Hanks, David; Gladden, Roy; Wood, Eric

    2004-01-01

    Multi-Mission Telecom Analysis Tool (MMTAT) is a C-language computer program for analyzing proposed spacecraft telecommunication systems. MMTAT utilizes parameterized input and computational models that can be run on standard desktop computers to perform fast and accurate analyses of telecommunication links. MMTAT is easy to use and can easily be integrated with other software applications and run as part of almost any computational simulation. It is distributed as either a stand-alone application program with a graphical user interface or a linkable library with a well-defined set of application programming interface (API) calls. As a stand-alone program, MMTAT provides both textual and graphical output. The graphs make it possible to understand, quickly and easily, how telecommunication performance varies with variations in input parameters. A delimited text file that can be read by any spreadsheet program is generated at the end of each run. The API in the linkable-library form of MMTAT enables the user to control simulation software and to change parameters during a simulation run. Results can be retrieved either at the end of a run or by use of a function call at any time step.

  4. Analyzing nocturnal noise stratification.

    PubMed

    Rey Gozalo, Guillermo; Barrigón Morillas, Juan Miguel; Gómez Escobar, Valentín

    2014-05-01

    Pollution associated to traffic can be considered as one of the most relevant pollution sources in our cities; noise is one of the major components of traffic pollution; thus, efforts are necessary to search adequate noise assessment methods and low pollution city designs. Different methods have been proposed for the evaluation of noise in cities, including the categorization method, which is based on the functionality concept. Until now, this method has only been studied (with encouraging results) for short-term, diurnal measurements, but nocturnal noise presents a behavior clearly different on respect to the diurnal one. In this work 45 continuous measurements of approximately one week each in duration are statistically analyzed to identify differences between the proposed categories. The results show that the five proposed categories highlight the noise stratification of the studied city in each period of the day (day, evening, and night). A comparison of the continuous measurements with previous short-term measurements indicates that the latter can be a good approximation of the former in diurnal period, reducing the resource expenditure for noise evaluation. Annoyance estimated from the measured noise levels was compared with the response of population obtained from a questionnaire with good agreement. The categorization method can yield good information about the distribution of a pollutant associated to traffic in our cities in each period of the day and, therefore, is a powerful tool for town planning and the design of pollution prevention policies.

  5. PULSE HEIGHT ANALYZER

    DOEpatents

    Johnstone, C.W.

    1958-01-21

    An anticoincidence device is described for a pair of adjacent channels of a multi-channel pulse height analyzer for preventing the lower channel from generating a count pulse in response to an input pulse when the input pulse has sufficient magnitude to reach the upper level channel. The anticoincidence circuit comprises a window amplifier, upper and lower level discriminators, and a biased-off amplifier. The output of the window amplifier is coupled to the inputs of the discriminators, the output of the upper level discriminator is connected to the resistance end of a series R-C network, the output of the lower level discriminator is coupled to the capacitance end of the R-C network, and the grid of the biased-off amplifier is coupled to the junction of the R-C network. In operation each discriminator produces a negative pulse output when the input pulse traverses its voltage setting. As a result of the connections to the R-C network, a trigger pulse will be sent to the biased-off amplifier when the incoming pulse level is sufficient to trigger only the lower level discriminator.

  6. PULSE HEIGHT ANALYZER

    DOEpatents

    Goldsworthy, W.W.

    1958-06-01

    A differential pulse-height discriminator circuit is described which is readily adaptable for operation in a single-channel pulse-height analyzer. The novel aspect of the circuit lies in the specific arrangement of differential pulse-height discriminator which includes two pulse-height discriminators having a comnnon input and an anticoincidence circuit having two interconnected vacuum tubes with a common cathode resistor. Pulses from the output of one discriminator circuit are delayed and coupled to the grid of one of the anticoincidence tubes by a resistor. The output pulses from the other discriminator circuit are coupled through a cathode follower circuit, which has a cathode resistor of such value as to provide a long time constant with the interelectrode capacitance of the tube, to lenthen the output pulses. The pulses are then fed to the grid of the other anticoincidence tube. With such connections of the circuits, only when the incoming pulse has a pesk value between the operating levels of the two discriminators does an output pulse occur from the anticoincidence circuit.

  7. Lorentz force particle analyzer

    NASA Astrophysics Data System (ADS)

    Wang, Xiaodong; Thess, André; Moreau, René; Tan, Yanqing; Dai, Shangjun; Tao, Zhen; Yang, Wenzhi; Wang, Bo

    2016-07-01

    A new contactless technique is presented for the detection of micron-sized insulating particles in the flow of an electrically conducting fluid. A transverse magnetic field brakes this flow and tends to become entrained in the flow direction by a Lorentz force, whose reaction force on the magnetic-field-generating system can be measured. The presence of insulating particles suspended in the fluid produce changes in this Lorentz force, generating pulses in it; these pulses enable the particles to be counted and sized. A two-dimensional numerical model that employs a moving mesh method demonstrates the measurement principle when such a particle is present. Two prototypes and a three-dimensional numerical model are used to demonstrate the feasibility of a Lorentz force particle analyzer (LFPA). The findings of this study conclude that such an LFPA, which offers contactless and on-line quantitative measurements, can be applied to an extensive range of applications. These applications include measurements of the cleanliness of high-temperature and aggressive molten metal, such as aluminum and steel alloys, and the clean manufacturing of semiconductors.

  8. TEAMS Model Analyzer

    NASA Technical Reports Server (NTRS)

    Tijidjian, Raffi P.

    2010-01-01

    The TEAMS model analyzer is a supporting tool developed to work with models created with TEAMS (Testability, Engineering, and Maintenance System), which was developed by QSI. In an effort to reduce the time spent in the manual process that each TEAMS modeler must perform in the preparation of reporting for model reviews, a new tool has been developed as an aid to models developed in TEAMS. The software allows for the viewing, reporting, and checking of TEAMS models that are checked into the TEAMS model database. The software allows the user to selectively model in a hierarchical tree outline view that displays the components, failure modes, and ports. The reporting features allow the user to quickly gather statistics about the model, and generate an input/output report pertaining to all of the components. Rules can be automatically validated against the model, with a report generated containing resulting inconsistencies. In addition to reducing manual effort, this software also provides an automated process framework for the Verification and Validation (V&V) effort that will follow development of these models. The aid of such an automated tool would have a significant impact on the V&V process.

  9. Prevalence of heroin markers in urine for pain management patients.

    PubMed

    Knight, Julie; Puet, Brandi L; DePriest, Anne; Heltsley, Rebecca; Hild, Cheryl; Black, David L; Robert, Timothy; Caplan, Yale H; Cone, Edward J

    2014-10-01

    Surveys of current trends indicate heroin abuse is associated with nonmedical use of pain relievers. Consequently, there is an interest in evaluating the presence of heroin-specific markers in chronic pain patients who are prescribed controlled substances. A total of 926,084 urine specimens from chronic pain patients were tested for heroin/diacetylmorphine (DAM), 6-acetylmorphine (6AM), 6-acetylcodeine (6AC), codeine (COD), and morphine (MOR). Heroin and markers were analyzed using liquid chromatography tandem mass spectrometry (LC-MS-MS). Opiates were analyzed following hydrolysis using LC-MS-MS. The prevalence of heroin use was 0.31%, as 2871 were positive for one or more heroin-specific markers including DAM, 6AM, or 6AC (a known contaminant of illicit heroin). Of these, 1884 were additionally tested for the following markers of illicit drug use: 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA), methamphetamine (MAMP), 11-nor-9-carboxy-Δ(9)-tetracannabinol (THCCOOH), and benzoylecgonine (BZE); 654 (34.7%) had positive findings for one or more of these analytes. The overall prevalence of heroin markers were as follows: DAM 1203 (41.9%), 6AM 2570 (89.5%), 6AC 1082 (37.7%). MOR was present in 2194 (76.4%) and absent (multiple heroin markers may be useful to assess for

  10. Digital Microfluidics Sample Analyzer

    NASA Technical Reports Server (NTRS)

    Pollack, Michael G.; Srinivasan, Vijay; Eckhardt, Allen; Paik, Philip Y.; Sudarsan, Arjun; Shenderov, Alex; Hua, Zhishan; Pamula, Vamsee K.

    2010-01-01

    Three innovations address the needs of the medical world with regard to microfluidic manipulation and testing of physiological samples in ways that can benefit point-of-care needs for patients such as premature infants, for which drawing of blood for continuous tests can be life-threatening in their own right, and for expedited results. A chip with sample injection elements, reservoirs (and waste), droplet formation structures, fluidic pathways, mixing areas, and optical detection sites, was fabricated to test the various components of the microfluidic platform, both individually and in integrated fashion. The droplet control system permits a user to control droplet microactuator system functions, such as droplet operations and detector operations. Also, the programming system allows a user to develop software routines for controlling droplet microactuator system functions, such as droplet operations and detector operations. A chip is incorporated into the system with a controller, a detector, input and output devices, and software. A novel filler fluid formulation is used for the transport of droplets with high protein concentrations. Novel assemblies for detection of photons from an on-chip droplet are present, as well as novel systems for conducting various assays, such as immunoassays and PCR (polymerase chain reaction). The lab-on-a-chip (a.k.a., lab-on-a-printed-circuit board) processes physiological samples and comprises a system for automated, multi-analyte measurements using sub-microliter samples of human serum. The invention also relates to a diagnostic chip and system including the chip that performs many of the routine operations of a central labbased chemistry analyzer, integrating, for example, colorimetric assays (e.g., for proteins), chemiluminescence/fluorescence assays (e.g., for enzymes, electrolytes, and gases), and/or conductometric assays (e.g., for hematocrit on plasma and whole blood) on a single chip platform.

  11. Serotonin, neural markers, and memory.

    PubMed

    Meneses, Alfredo

    2015-01-01

    Diverse neuropsychiatric disorders present dysfunctional memory and no effective treatment exits for them; likely as result of the absence of neural markers associated to memory. Neurotransmitter systems and signaling pathways have been implicated in memory and dysfunctional memory; however, their role is poorly understood. Hence, neural markers and cerebral functions and dysfunctions are revised. To our knowledge no previous systematic works have been published addressing these issues. The interactions among behavioral tasks, control groups and molecular changes and/or pharmacological effects are mentioned. Neurotransmitter receptors and signaling pathways, during normal and abnormally functioning memory with an emphasis on the behavioral aspects of memory are revised. With focus on serotonin, since as it is a well characterized neurotransmitter, with multiple pharmacological tools, and well characterized downstream signaling in mammals' species. 5-HT1A, 5-HT4, 5-HT5, 5-HT6, and 5-HT7 receptors as well as SERT (serotonin transporter) seem to be useful neural markers and/or therapeutic targets. Certainly, if the mentioned evidence is replicated, then the translatability from preclinical and clinical studies to neural changes might be confirmed. Hypothesis and theories might provide appropriate limits and perspectives of evidence.

  12. Serotonin, neural markers, and memory

    PubMed Central

    Meneses, Alfredo

    2015-01-01

    Diverse neuropsychiatric disorders present dysfunctional memory and no effective treatment exits for them; likely as result of the absence of neural markers associated to memory. Neurotransmitter systems and signaling pathways have been implicated in memory and dysfunctional memory; however, their role is poorly understood. Hence, neural markers and cerebral functions and dysfunctions are revised. To our knowledge no previous systematic works have been published addressing these issues. The interactions among behavioral tasks, control groups and molecular changes and/or pharmacological effects are mentioned. Neurotransmitter receptors and signaling pathways, during normal and abnormally functioning memory with an emphasis on the behavioral aspects of memory are revised. With focus on serotonin, since as it is a well characterized neurotransmitter, with multiple pharmacological tools, and well characterized downstream signaling in mammals' species. 5-HT1A, 5-HT4, 5-HT5, 5-HT6, and 5-HT7 receptors as well as SERT (serotonin transporter) seem to be useful neural markers and/or therapeutic targets. Certainly, if the mentioned evidence is replicated, then the translatability from preclinical and clinical studies to neural changes might be confirmed. Hypothesis and theories might provide appropriate limits and perspectives of evidence. PMID:26257650

  13. Whole blood coagulation analyzers.

    PubMed

    1997-08-01

    Whole blood Coagulation analyzers (WBCAs) are widely used point-of-care (POC) testing devices found primarily in cardiothoracic surgical suites and cardia catheterization laboratories. Most of these devices can perform a number of coagulation tests that provide information about a patient's blood clotting status. Clinicians use the results of the WBCA tests, which are available minutes after applying a blood sample, primarily to monitor the effectiveness of heparin therapy--an anticoagulation therapy used during cardiopulmonary bypass (CPB) surgery, angioplasty, hemodialysis, and other clinical procedures. In this study we evaluated five WBCAs from four suppliers. Our testing focused on the applications for which WBCAs are primarily used: Monitoring moderate to high heparin levels, as would be required, for example, during CPB are angioplasty. For this function, WCBAs are typically used to perform an activated clotting time (ACT) test or, as one supplier refers to its test, a heparin management test (HMT). All models included in this study offered an ACT test or an HMT. Monitoring low heparin levels, as would be required, for example,during hemodialysis. For this function, WBCAs would normally be used to perform either a low-range ACT (LACT) test or a whole blood activated partial thromboplastin time (WBAPTT) test. Most of the evaluated units could perform at least one of these tests; one unit did not offer either test and was therefore not rated for this application. We rated and ranked each evaluated model separately for each of these two applications. In addition, we provided a combined rating and ranking that considers the units' appropriateness for performing both application. We based our conclusions on a unit's performance and humans factor design, as determined by our testing, and on its five-year life-cycle cost, as determined by our net present value (NPV) analysis. While we rated all evaluated units acceptable for each appropriate category, we did

  14. Soft Decision Analyzer

    NASA Technical Reports Server (NTRS)

    Steele, Glen; Lansdowne, Chatwin; Zucha, Joan; Schlensinger, Adam

    2013-01-01

    The Soft Decision Analyzer (SDA) is an instrument that combines hardware, firmware, and software to perform realtime closed-loop end-to-end statistical analysis of single- or dual- channel serial digital RF communications systems operating in very low signal-to-noise conditions. As an innovation, the unique SDA capabilities allow it to perform analysis of situations where the receiving communication system slips bits due to low signal-to-noise conditions or experiences constellation rotations resulting in channel polarity in versions or channel assignment swaps. SDA s closed-loop detection allows it to instrument a live system and correlate observations with frame, codeword, and packet losses, as well as Quality of Service (QoS) and Quality of Experience (QoE) events. The SDA s abilities are not confined to performing analysis in low signal-to-noise conditions. Its analysis provides in-depth insight of a communication system s receiver performance in a variety of operating conditions. The SDA incorporates two techniques for identifying slips. The first is an examination of content of the received data stream s relation to the transmitted data content and the second is a direct examination of the receiver s recovered clock signals relative to a reference. Both techniques provide benefits in different ways and allow the communication engineer evaluating test results increased confidence and understanding of receiver performance. Direct examination of data contents is performed by two different data techniques, power correlation or a modified Massey correlation, and can be applied to soft decision data widths 1 to 12 bits wide over a correlation depth ranging from 16 to 512 samples. The SDA detects receiver bit slips within a 4 bits window and can handle systems with up to four quadrants (QPSK, SQPSK, and BPSK systems). The SDA continuously monitors correlation results to characterize slips and quadrant change and is capable of performing analysis even when the

  15. Regolith Evolved Gas Analyzer

    NASA Technical Reports Server (NTRS)

    Hoffman, John H.; Hedgecock, Jud; Nienaber, Terry; Cooper, Bonnie; Allen, Carlton; Ming, Doug

    2000-01-01

    The Regolith Evolved Gas Analyzer (REGA) is a high-temperature furnace and mass spectrometer instrument for determining the mineralogical composition and reactivity of soil samples. REGA provides key mineralogical and reactivity data that is needed to understand the soil chemistry of an asteroid, which then aids in determining in-situ which materials should be selected for return to earth. REGA is capable of conducting a number of direct soil measurements that are unique to this instrument. These experimental measurements include: (1) Mass spectrum analysis of evolved gases from soil samples as they are heated from ambient temperature to 900 C; and (2) Identification of liberated chemicals, e.g., water, oxygen, sulfur, chlorine, and fluorine. REGA would be placed on the surface of a near earth asteroid. It is an autonomous instrument that is controlled from earth but does the analysis of regolith materials automatically. The REGA instrument consists of four primary components: (1) a flight-proven mass spectrometer, (2) a high-temperature furnace, (3) a soil handling system, and (4) a microcontroller. An external arm containing a scoop or drill gathers regolith samples. A sample is placed in the inlet orifice where the finest-grained particles are sifted into a metering volume and subsequently moved into a crucible. A movable arm then places the crucible in the furnace. The furnace is closed, thereby sealing the inner volume to collect the evolved gases for analysis. Owing to the very low g forces on an asteroid compared to Mars or the moon, the sample must be moved from inlet to crucible by mechanical means rather than by gravity. As the soil sample is heated through a programmed pattern, the gases evolved at each temperature are passed through a transfer tube to the mass spectrometer for analysis and identification. Return data from the instrument will lead to new insights and discoveries including: (1) Identification of the molecular masses of all of the gases

  16. [Markers of prostatic carcinoma].

    PubMed

    Safarík, L

    1998-08-31

    Author gives the survey of markers at prostate carcinoma, that has been known so far, their origin and the use in experiment and clinical praxis. He discusses their sensitivity and specificity and shows the perspective of new markers discovered and used in the praxis on basis of molecular genetics.

  17. SKY assessment of two karyotypes with 0-6 supernumerary marker/ring chromosomes and review of previously reported cases with two or more markers.

    PubMed

    Reddy, Kavita S; Wang, Shirong; Groh, Shannon; Gonatos, John

    2003-04-15

    maps to 7q11.23, SNRPN gene that maps to 15q11.2, and TUPLE gene that maps to 22q11.2 did not give a signal on the markers. As expected for a majority of ring chromosomes, the pan telomere probe did not hybridize to any of the markers. This highly unusual karyotype was confirmed in the buccal epithelium using a mix of centromere 7 and 15 probes and the combination 14/22 probe. The ratio of additional FISH signals in the buccal mucosal cells was comparable to the ratios observed in the peripheral blood. In this study, we have attempted to consolidate the data on >/=2 marker cases to understand the analysis constraints, the range of clinical abnormalities, and the mechanisms involved. The literature was surveyed for multiple markers cases. A majority of the reported cases had two markers, either derived from the same chromosome or from two different chromosomes or two cell lines with different markers derived from the same chromosome. Cases with three or more markers were rare. The nature and extent of euchromatin content of the multiple markers appears to determine the phenotype. Frequently, multiple marker cases had small to minute markers. The clinical presentation varied from mild to severe. While two bisatellited markers may be associated with infertility, the phenotype in other cases ranged from borderline intelligence and mild dysmorphism to developmental delay, mental retardation, and congenital abnormalities. Copyright 2003 Wiley-Liss, Inc.

  18. Analyzes Data from Semiconductor Wafers

    SciTech Connect

    Breiland, William G.

    2002-07-23

    This program analyzes reflectance data from semiconductor wafers taken during the deposition or evolution of a thin film, typically via chemical vapor deposition (CVD) or molecular beam epitaxy (MBE). It is used to determine the growth rate and optical constants of the deposited thin films using a virtual interface concept. Growth rates and optical constants of multiple-layer structures is possible by selecting appropriate sections in the reflectance vs time waveform. No prior information or estimates of growth rates and materials properties is required if an absolute reflectance waveform is used. If the optical constants of a thin film are known, then the growth rate may be extracted from a relative reflectance data set. The analysis is valid for either s or p polarized light at any incidence angle and wavelength. The analysis package is contained within an easy-to-use graphical user interface. The program is based on the algorighm described in the following two publications: W.G. Breiland and K.P. Killen, J. Appl. Phys. 78 (1995) 6726, and W. G. Breiland, H.Q. Hou, B.E. Hammons, and J.F. Klem, Proc. XXVIII SOTAPOCS Symp. Electrochem. Soc. San Diego, May 3-8, 1998. It relies on the fact that any multiple-layer system has a reflectance spectrum that is mathematically equivalent to a single-layer thin film on a virtual substrate. The program fits the thin film reflectance with five adjustable parameters: 1) growth rate, 2) real part of complex refractive index, 3) imaginary part of refractive index, 4) amplitude of virtual interface reflectance, 5) phase of virtual interface reflectance.

  19. Multiple Pregnancy

    MedlinePlus

    ... Education & Events Advocacy For Patients About ACOG Multiple Pregnancy Home For Patients Search FAQs Multiple Pregnancy Page ... Multiple Pregnancy FAQ188, July 2015 PDF Format Multiple Pregnancy Pregnancy How does multiple pregnancy occur? What are ...

  20. Development of new molecular markers for the Colletotrichum genus using RetroCl1 sequences.

    PubMed

    Dos Santos, Leandro Vieira; de Queiroz, Marisa Vieira; Santana, Mateus Ferreira; Soares, Marcos Antônio; de Barros, Everaldo Gonçalves; de Araújo, Elza Fernandes; Langin, Thierry

    2012-03-01

    A nonautonomous element of 624 bp, called RetroCl1 (Retroelement Colletotrichum lindemuthianum 1), was identified in the plant pathogenic fungus Colletotrichum lindemuthianum. RetroCl1 contains terminal direct repeats (223 bp) that are surrounded by CTAGT sequences. It has a short internal domain of 178 bp and shows characteristics of terminal-repeat retrotransposon in miniature (TRIM) family. We used RetroCl1 sequence to develop molecular markers for the Colletotrichum genus. IRAP (Inter-Retrotransposon Amplified Polymorphism) and REMAP (Retrotransposon-Microsatellite Amplified Polymorphism) markers were used to analyze the genetic diversity of C. lindemuthianum. Fifty-four isolates belonging to different races were used. A total of 45 loci were amplified. The Nei index showed significant differences among the populations divided according to race, indicating that they are structured according to pathotype. No clear correlation between IRAP and REMAP markers with pathogenic characterization was found. C. lindemuthianum has high genetic diversity, and the analysis of molecular variance showed that 51% of variability is found among the populations of different races. The markers were also tested in different Colletotrichum species. In every case, multiple bands were amplified, indicating that these markers can be successfully used in different species belonging to the Colletotrichum genus.

  1. CombiROC: an interactive web tool for selecting accurate marker combinations of omics data.

    PubMed

    Mazzara, Saveria; Rossi, Riccardo L; Grifantini, Renata; Donizetti, Simone; Abrignani, Sergio; Bombaci, Mauro

    2017-03-30

    Diagnostic accuracy can be improved considerably by combining multiple markers, whose performance in identifying diseased subjects is usually assessed via receiver operating characteristic (ROC) curves. The selection of multimarker signatures is a complicated process that requires integration of data signatures with sophisticated statistical methods. We developed a user-friendly tool, called CombiROC, to help researchers accurately determine optimal markers combinations from diverse omics methods. With CombiROC data from different domains, such as proteomics and transcriptomics, can be analyzed using sensitivity/specificity filters: the number of candidate marker panels rising from combinatorial analysis is easily optimized bypassing limitations imposed by the nature of different experimental approaches. Leaving to the user full control on initial selection stringency, CombiROC computes sensitivity and specificity for all markers combinations, performances of best combinations and ROC curves for automatic comparisons, all visualized in a graphic interface. CombiROC was designed without hard-coded thresholds, allowing a custom fit to each specific data: this dramatically reduces the computational burden and lowers the false negative rates given by fixed thresholds. The application was validated with published data, confirming the marker combination already originally described or even finding new ones. CombiROC is a novel tool for the scientific community freely available at http://CombiROC.eu.

  2. CombiROC: an interactive web tool for selecting accurate marker combinations of omics data

    PubMed Central

    Mazzara, Saveria; Rossi, Riccardo L.; Grifantini, Renata; Donizetti, Simone; Abrignani, Sergio; Bombaci, Mauro

    2017-01-01

    Diagnostic accuracy can be improved considerably by combining multiple markers, whose performance in identifying diseased subjects is usually assessed via receiver operating characteristic (ROC) curves. The selection of multimarker signatures is a complicated process that requires integration of data signatures with sophisticated statistical methods. We developed a user-friendly tool, called CombiROC, to help researchers accurately determine optimal markers combinations from diverse omics methods. With CombiROC data from different domains, such as proteomics and transcriptomics, can be analyzed using sensitivity/specificity filters: the number of candidate marker panels rising from combinatorial analysis is easily optimized bypassing limitations imposed by the nature of different experimental approaches. Leaving to the user full control on initial selection stringency, CombiROC computes sensitivity and specificity for all markers combinations, performances of best combinations and ROC curves for automatic comparisons, all visualized in a graphic interface. CombiROC was designed without hard-coded thresholds, allowing a custom fit to each specific data: this dramatically reduces the computational burden and lowers the false negative rates given by fixed thresholds. The application was validated with published data, confirming the marker combination already originally described or even finding new ones. CombiROC is a novel tool for the scientific community freely available at http://CombiROC.eu. PMID:28358118

  3. GMATA: An Integrated Software Package for Genome-Scale SSR Mining, Marker Development and Viewing.

    PubMed

    Wang, Xuewen; Wang, Le

    2016-01-01

    Simple sequence repeats (SSRs), also referred to as microsatellites, are highly variable tandem DNAs that are widely used as genetic markers. The increasing availability of whole-genome and transcript sequences provides information resources for SSR marker development. However, efficient software is required to efficiently identify and display SSR information along with other gene features at a genome scale. We developed novel software package Genome-wide Microsatellite Analyzing Tool Package (GMATA) integrating SSR mining, statistical analysis and plotting, marker design, polymorphism screening and marker transferability, and enabled simultaneously display SSR markers with other genome features. GMATA applies novel strategies for SSR analysis and primer design in large genomes, which allows GMATA to perform faster calculation and provides more accurate results than existing tools. Our package is also capable of processing DNA sequences of any size on a standard computer. GMATA is user friendly, only requires mouse clicks or types inputs on the command line, and is executable in multiple computing platforms. We demonstrated the application of GMATA in plants genomes and reveal a novel distribution pattern of SSRs in 15 grass genomes. The most abundant motifs are dimer GA/TC, the A/T monomer and the GCG/CGC trimer, rather than the rich G/C content in DNA sequence. We also revealed that SSR count is a linear to the chromosome length in fully assembled grass genomes. GMATA represents a powerful application tool that facilitates genomic sequence analyses. GAMTA is freely available at http://sourceforge.net/projects/gmata/?source=navbar.

  4. Molecular Marker Systems for Oenothera Genetics

    PubMed Central

    Rauwolf, Uwe; Golczyk, Hieronim; Meurer, Jörg; Herrmann, Reinhold G.; Greiner, Stephan

    2008-01-01

    The genus Oenothera has an outstanding scientific tradition. It has been a model for studying aspects of chromosome evolution and speciation, including the impact of plastid nuclear co-evolution. A large collection of strains analyzed during a century of experimental work and unique genetic possibilities allow the exchange of genetically definable plastids, individual or multiple chromosomes, and/or entire haploid genomes (Renner complexes) between species. However, molecular genetic approaches for the genus are largely lacking. In this study, we describe the development of efficient PCR-based marker systems for both the nuclear genome and the plastome. They allow distinguishing individual chromosomes, Renner complexes, plastomes, and subplastomes. We demonstrate their application by monitoring interspecific exchanges of genomes, chromosome pairs, and/or plastids during crossing programs, e.g., to produce plastome–genome incompatible hybrids. Using an appropriate partial permanent translocation heterozygous hybrid, linkage group 7 of the molecular map could be assigned to chromosome 9·8 of the classical Oenothera map. Finally, we provide the first direct molecular evidence that homologous recombination and free segregation of chromosomes in permanent translocation heterozygous strains is suppressed. PMID:18791241

  5. Adiposity markers and risk of coronary heart disease in patients with type 2 diabetes mellitus.

    PubMed

    Tonding, Simone F; Silva, Flávia M; Antonio, Juliana P; Azevedo, Mirela J; Canani, Luis Henrique S; Almeida, Jussara C

    2014-12-23

    This cross-sectional study aimed to evaluating the association between body adiposity markers and high-risk of coronary heart disease (CHD) in patients with type 2 diabetes. Recent adiposity markers [waist-to-height ratio, conicity index (C-index) and body adiposity index] and traditional markers [BMI, waist circumference and waist-to-hip ratio (WHR)] were measured. The 10-year risk of fatal CHD was estimated according to UKPDS risk engine scores. Patients were divided into high (CHD risk ≥20%; n = 99) or low-moderate (CHD risk <20%; n = 321) risk groups. Multiple logistic regression models were performed to analyze associations between CHD risk (outcome) and adiposity markers. A total of 420 patients with type 2 diabetes (61.9 ± 9.5 years; 53.5% females; HbA1c 7.6 ± 1.6%) were evaluated. The high risk group had greater proportions of elevated C-index and BMI values than patients with low-moderate risk. No between-group differences in other adiposity markers were observed. In multiple logistic regression models, only C-index values ≥1.35 were associated with CHD risk >20% (OR = 1.69; 95% CI 1.03-2.78; P = 0.039) after adjusting for confounders (sedentary lifestyle, diabetic nephropathy, serum creatinine, and diabetes duration). The association between WHR and CHD risk did not hold in this sample. The C-index was the body adiposity marker best associated with high risk of fatal CHD in these patients with type 2 diabetes.

  6. Ultra-performance liquid chromatography/multiple reaction monitoring mass spectrometry quantification of trastuzumab in human serum by selective monitoring of a specific peptide marker from the antibody complementarity-determining regions.

    PubMed

    Russo, R; Rega, C; Caporale, A; Tonon, G; Scaramuzza, S; Selis, F; Ruvo, M; Chambery, A

    2017-07-30

    Because of the large molecular weight, the structural complexity and the similarity with endogenous immunoglobulins present in high concentrations, in vivo quantitative studies with therapeutic monoclonal antibodies are particularly challenging. In this work, an UPLC/MRM MS-based methodology is described for the quantification of trastuzumab in human serum by monitoring a novel specific peptide marker located within its heavy chain Complementarity-Determining Region (CDR). For maximum sensitivity and selectivity, specific transitions of this diagnostic proteotypic peptide were optimized and monitored at m/z 364.1 → 437.3 (quantitation ion) and m/z 364.1 → 358.0 (confirmation ion). As a proof-of-concept, the methodology was applied to the determination of trastuzumab in human serum over a clinically relevant range from 0.02 to 200 μg/mL. The methodology has been evaluated in terms of specificity, linearity, accuracy, precision, detection and quantitation limits. An excellent linear response has been obtained in the range from 0.036 to 3.6 fmol/μL for the standard peptide and from 0.03 to 285 fmol/μL for the trastuzumab in human serum with typical R(2) values of 0.99. The limit of detection (LOD) and limit of quantification (LOQ) are 0.005 fmol/μL and 0.05 fmol/μL, respectively, with mean bias and RSD values of 18% and 1%, respectively, for quality control samples. The strategy used to set up the UPLC/MRM MS methodology based on monitoring specific peptide markers within CDRs can be potentially applied to the detection and quantification of other humanized or human mAbs in biological fluids. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  7. Systems Analyze Water Quality in Real Time

    NASA Technical Reports Server (NTRS)

    2010-01-01

    A water analyzer developed under Small Business Innovation Research (SBIR) contracts with Kennedy Space Center now monitors treatment processes at water and wastewater facilities around the world. Originally designed to provide real-time detection of nutrient levels in hydroponic solutions for growing plants in space, the ChemScan analyzer, produced by ASA Analytics Inc., of Waukesha, Wisconsin, utilizes spectrometry and chemometric algorithms to automatically analyze multiple parameters in the water treatment process with little need for maintenance, calibration, or operator intervention. The company has experienced a compound annual growth rate of 40 percent over its 15-year history as a direct result of the technology's success.

  8. Identification of fecal contamination sources in water using host-associated markers.

    PubMed

    Krentz, Corinne A; Prystajecky, Natalie; Isaac-Renton, Judith

    2013-03-01

    In British Columbia, Canada, drinking water is tested for total coliforms and Escherichia coli, but there is currently no routine follow-up testing to investigate fecal contamination sources in samples that test positive for indicator bacteria. Reliable microbial source tracking (MST) tools to rapidly test water samples for multiple fecal contamination markers simultaneously are currently lacking. The objectives of this study were (i) to develop a qualitative MST tool to identify fecal contamination from different host groups, and (ii) to evaluate the MST tool using water samples with evidence of fecal contamination. Singleplex and multiplex polymerase chain reaction (PCR) were used to test (i) water from polluted sites and (ii) raw and drinking water samples for presence of bacterial genetic markers associated with feces from humans, cattle, seagulls, pigs, chickens, and geese. The multiplex MST assay correctly identified suspected contamination sources in contaminated waterways, demonstrating that this test may have utility for heavily contaminated sites. Most raw and drinking water samples analyzed using singleplex PCR contained at least one host-associated marker. Singleplex PCR was capable of detecting host-associated markers in small sample volumes and is therefore a promising tool to further analyze water samples submitted for routine testing and provide information useful for water quality management.

  9. Apoptotic markers in protozoan parasites

    PubMed Central

    2010-01-01

    The execution of the apoptotic death program in metazoans is characterized by a sequence of morphological and biochemical changes that include cell shrinkage, presentation of phosphatidylserine at the cell surface, mitochondrial alterations, chromatin condensation, nuclear fragmentation, membrane blebbing and the formation of apoptotic bodies. Methodologies for measuring apoptosis are based on these markers. Except for membrane blebbing and formation of apoptotic bodies, all other events have been observed in most protozoan parasites undergoing cell death. However, while techniques exist to detect these markers, they are often optimised for metazoan cells and therefore may not pick up subtle differences between the events occurring in unicellular organisms and multi-cellular organisms. In this review we discuss the markers most frequently used to analyze cell death in protozoan parasites, paying special attention to changes in cell morphology, mitochondrial activity, chromatin structure and plasma membrane structure/permeability. Regarding classical regulators/executors of apoptosis, we have reviewed the present knowledge of caspase-like and nuclease activities. PMID:21062457

  10. CHEMICAL MARKERS OF HUMAN WASTE ...

    EPA Pesticide Factsheets

    Giving public water authorities another tool to monitor and measure levels of human waste contamination of waters simply and rapidly would enhance public protection. Most of the methods used today detect such contamination by quantifying microbes occurring in feces in high enough densities that they can be measured easily. However, most of these microbes, for example E. coli, do not serve as specific markers for any one host species and many can have origins other than feces. As an alternative, chemicals shed in feces and urine might be used to detect human waste contamination of environmental waters. One potential chemical marker of human waste is the compound urobilin. Urobilin is one of the final by-products of hemoglobin breakdown. Urobilin is excreted in both the urine and feces from many mammals, particularly humans. Source waters from 21 sites in New England, Nevada, and Michigan were extracted using hydrophilic-lipophilic balance (HLB) cartridges and then analyzed by high performance liquid chromatography-electrospray-mass spectrometry (HPLC-ES-MS). As a marker of human waste, urobilin was detected in many of the source waters at concentrations ranging from not detectable to 300 ng/L. Besides urobilin, zithromycin, an antibiotic widely prescribed for human-use only in the US, was also detected in many of these waters, with concentrations ranging from not detectable to 77 ng/L. This methodology, using both urobilin and azithromycin (or any other human-use

  11. Neural activity, memory, and dementias: serotonergic markers.

    PubMed

    Meneses, Alfredo

    2017-04-01

    Dysfunctional memory seems to be a key component of diverse dementias and other neuropsychiatric disorders; unfortunately, no effective treatment exists for this, probably because of the absence of neural biomarkers accompanying it. Diverse neurotransmission systems have been implicated in memory, including serotonin or 5-hydroxytryptamine (5-HT). There are multiple serotonergic pharmacological tools, well-characterized downstream signaling in mammals' species and neural markers providing new insights into memory functions and dysfunctions. Serotonin in mammal species has multiple neural markers, including receptors (5-HT1-7), serotonin transporter, and volume transmission, which are present in brain areas involved in memory. Memory, amnesia, and forgetting modify serotonergic markers; this influence is bidirectional. Evidence shows insights and therapeutic targets and diverse approaches support the translatability of using neural markers and cerebral functions and dysfunctions, including memory formation and amnesia. For instance, 5-HT2A/2B/2C, 5-HT4, and 5-HT6 receptors are involved in tau protein hyperphosphorylation in Alzheimer's disease. In addition, at least, 5-HT1A, 5-HT4, 5-HT6, and 5-HT7 receptors as well as serotonin transporter seem to be useful neural markers and therapeutic targets. Hence, available evidence supports the notion that several mechanisms cooperate to achieve synaptic plasticity or memory, including changes in the number of neurotransmitter receptors and transporters. Considering that memory is a key component of dementias, hence reversing or reducing memory deficits might positively affect them?

  12. Augmented Reality Marker Hiding with Texture Deformation.

    PubMed

    Kawai, Norihiko; Sato, Tomokazu; Nakashima, Yuta; Yokoya, Naokazu

    2016-10-19

    Augmented reality (AR) marker hiding is a technique to visually remove AR markers in a real-time video stream. A conventional approach transforms a background image with a homography matrix calculated on the basis of a camera pose and overlays the transformed image on an AR marker region in a real-time frame, assuming that the AR marker is on a planar surface. However, this approach may cause discontinuities in textures around the boundary between the marker and its surrounding area when the planar surface assumption is not satisfied. This paper proposes a method for AR marker hiding without discontinuities around texture boundaries even under nonplanar background geometry without measuring it. For doing this, our method estimates the dense motion in the marker's background by analyzing the motion of sparse feature points around it, together with a smooth motion assumption, and deforms the background image according to it. Our experiments demonstrate the effectiveness of the proposed method in various environments with different background geometries and textures.

  13. Meta-markers for the differential diagnosis of lung cancer and lung disease.

    PubMed

    Kim, Yong-In; Ahn, Jung-Mo; Sung, Hye-Jin; Na, Sang-Su; Hwang, Jaesung; Kim, Yongdai; Cho, Je-Yoel

    2016-10-04

    Misdiagnosis of lung cancer remains a serious problem due to the difficulty of distinguishing lung cancer from other respiratory lung diseases. As a result, the development of serum-based differential diagnostic biomarkers is in high demand. In this study, 198 clinical serum samples from non-cancer lung disease and lung cancer patients were analyzed using nLC-MRM-MS for the levels of seven lung cancer biomarker candidates. When the candidates were assessed individually, only SERPINEA4 showed statistically significant changes in the serum levels. The MRM results and clinical information were analyzed using a logistic regression analysis to select model for the best 'meta-marker', or combination of biomarkers for differential diagnosis. Also, under consideration of statistical interaction, variables having low significance as a single factor but statistically influencing on meta-marker model were selected. Using this probabilistic classification, the best meta-marker was determined to be made up of two proteins SERPINA4 and PON1 with age factor. This meta-marker showed an enhanced differential diagnostic capability (AUC=0.915) for distinguishing the two patient groups. Our results suggest that a statistical model can determine optimal meta-markers, which may have better specificity and sensitivity than a single biomarker and thus improve the differential diagnosis of lung cancer and lung disease patients. Diagnosing lung cancer commonly involves the use of radiographic methods. However, an imaging-based diagnosis may fail to differentiate lung cancer from non-cancerous lung disease. In this study, we examined several serum proteins in the sera of 198 lung cancer and non-cancerous lung disease patients by multiple-reaction monitoring. We then used a combination of variables to generate a meta-marker model that is useful as a differential diagnostic biomarker. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  14. Characterization and transferability of microsatellite markers of the cultivated peanut (Arachis hypogaea)

    PubMed Central

    Gimenes, Marcos A; Hoshino, Andrea A; Barbosa, Andrea VG; Palmieri, Dario A; Lopes, Catalina R

    2007-01-01

    Background The genus Arachis includes Arachis hypogaea (cultivated peanut) and wild species that are used in peanut breeding or as forage. Molecular markers have been employed in several studies of this genus, but microsatellite markers have only been used in few investigations. Microsatellites are very informative and are useful to assess genetic variability, analyze mating systems and in genetic mapping. The objectives of this study were to develop A. hypogaea microsatellite loci and to evaluate the transferability of these markers to other Arachis species. Results Thirteen loci were isolated and characterized using 16 accessions of A. hypogaea. The level of variation found in A. hypogaea using microsatellites was higher than with other markers. Cross-transferability of the markers was also high. Sequencing of the fragments amplified using the primer pair Ah11 from 17 wild Arachis species showed that almost all wild species had similar repeated sequence to the one observed in A. hypogaea. Sequence data suggested that there is no correlation between taxonomic relationship of a wild species to A. hypogaea and the number of repeats found in its microsatellite loci. Conclusion These results show that microsatellite primer pairs from A. hypogaea have multiple uses. A higher level of variation among A. hypogaea accessions can be detected using microsatellite markers in comparison to other markers, such as RFLP, RAPD and AFLP. The microsatellite primers of A. hypogaea showed a very high rate of transferability to other species of the genus. These primer pairs provide important tools to evaluate the genetic variability and to assess the mating system in Arachis species. PMID:17326826

  15. Fiducial Marker Placement

    MedlinePlus

    ... Media Computed Tomography (CT) - Body General Ultrasound Ultrasound - Prostate Introduction to Cancer Therapy (Radiation Oncology) Proton Therapy Stereotactic Radiosurgery (SRS) and Stereotactic Body Radiotherapy (SBRT) Images related to Fiducial Marker Placement Sponsored by ...

  16. Simultaneous analysis of T helper subsets (Th1, Th2, Th9, Th17, Th22, Tfh, Tr1 and Tregs) markers expression in periapical lesions reveals multiple cytokine clusters accountable for lesions activity and inactivity status.

    PubMed

    Araujo-Pires, Ana Claudia; Francisconi, Carolina Favaro; Biguetti, Claudia Cristina; Cavalla, Franco; Aranha, Andreza Maria Fabio; Letra, Ariadne; Trombone, Ana Paula Favaro; Faveri, Marcelo; Silva, Renato Menezes; Garlet, Gustavo Pompermaier

    2014-01-01

    Previous studies demonstrate that the balance between pro- and anti-inflammatory mediators determines the stable or progressive nature of periapical granulomas by modulating the balance of the osteoclastogenic factor RANKL and its antagonist OPG. However, the cytokine networks operating in the development of periapical lesions are quite more complex than what the simple pro- versus anti-inflammatory mediators' paradigm suggests. Here we simultaneously investigated the patterns of Th1, Th2, Th9, Th17, Th22, Thf, Tr1 and Tregs cytokines/markers expression in human periapical granulomas. The expression of TNF-α, IFN-γ, IL-17A, IL23, IL21, IL-33, IL-10, IL-4, IL-9, IL-22, FOXp3 markers (via RealTimePCR array) was accessed in active/progressive (N=40) versus inactive/stable (N=70) periapical granulomas (as determined by RANKL/OPG expression ratio), and also to compare these samples with a panel of control specimens (N=26). A cluster analysis of 13 cytokine levels was performed to examine possible clustering between the cytokines in a total of 110 granulomas. The expression of all target cytokines was higher in the granulomas than in control samples. TNF-α, IFN-γ, IL-17A and IL-21 mRNA levels were significantly higher in active granulomas, while in inactive lesions the expression levels of IL-4, IL-9, IL-10, IL-22 and FOXp3 were higher than in active granulomas. Five clusters were identified in inactive lesion groups, being the variance in the expression levels of IL-17, IL-10, FOXp3, IFN-γ, IL-9, IL-33 and IL-4 statistically significant (KW p<0.05). Three clusters were identified in active lesions, being the variance in the expression levels of IL-22, IL-10, IFN-γ, IL-17, IL-33, FOXp3, IL-21 and RANKL statistically significant (KW p<0.05). There is a clear dichotomy in the profile of cytokine expression in inactive and active periapical lesions. While the widespread cytokine expression seems to be a feature of chronic lesions, hierarchical cluster analysis

  17. Simultaneous analysis of T helper subsets (Th1, Th2, Th9, Th17, Th22, Tfh, Tr1 and Tregs) markers expression in periapical lesions reveals multiple cytokine clusters accountable for lesions activity and inactivity status

    PubMed Central

    ARAUJO-PIRES, Ana Claudia; FRANCISCONI, Carolina Favaro; BIGUETTI, Claudia Cristina; CAVALLA, Franco; ARANHA, Andreza Maria Fabio; LETRA, Ariadne; TROMBONE, Ana Paula Favaro; FAVERI, Marcelo; SILVA, Renato Menezes; GARLET, Gustavo Pompermaier

    2014-01-01

    Previous studies demonstrate that the balance between pro- and anti-inflammatory mediators determines the stable or progressive nature of periapical granulomas by modulating the balance of the osteoclastogenic factor RANKL and its antagonist OPG. However, the cytokine networks operating in the development of periapical lesions are quite more complex than what the simple pro- versus anti-inflammatory mediators' paradigm suggests. Here we simultaneously investigated the patterns of Th1, Th2, Th9, Th17, Th22, Thf, Tr1 and Tregs cytokines/markers expression in human periapical granulomas. Methods The expression of TNF-α, IFN-γ, IL-17A, IL23, IL21, IL-33, IL-10, IL-4, IL-9, IL-22, FOXp3 markers (via RealTimePCR array) was accessed in active/progressive (N=40) versus inactive/stable (N=70) periapical granulomas (as determined by RANKL/OPG expression ratio), and also to compare these samples with a panel of control specimens (N=26). A cluster analysis of 13 cytokine levels was performed to examine possible clustering between the cytokines in a total of 110 granulomas. Results The expression of all target cytokines was higher in the granulomas than in control samples. TNF-α, IFN-γ, IL-17A and IL-21 mRNA levels were significantly higher in active granulomas, while in inactive lesions the expression levels of IL-4, IL-9, IL-10, IL-22 and FOXp3 were higher than in active granulomas. Five clusters were identified in inactive lesion groups, being the variance in the expression levels of IL-17, IL-10, FOXp3, IFN-γ, IL-9, IL-33 and IL-4 statistically significant (KW p<0.05). Three clusters were identified in active lesions, being the variance in the expression levels of IL-22, IL-10, IFN-γ, IL-17, IL-33, FOXp3, IL-21 and RANKL statistically significant (KW p<0.05). Conclusion There is a clear dichotomy in the profile of cytokine expression in inactive and active periapical lesions. While the widespread cytokine expression seems to be a feature of chronic lesions

  18. Alcoholism: Current Marker Research

    DTIC Science & Technology

    1984-03-01

    genetically determined characteristics such as color blindness and blood type . GENETIC MARKER STUDIES In 1966 Dr. Cruz-Coke and Dr. Varela reported that...and recovery from severe alcoholism symptoms. ■󈧒:584-587) Blood - typing marker studies have produced similar mixed results. One study published in...1959 showed a high correlation among 939 alcoholics and blood type A. (20:4 60-4 61) A similar study in 1973 reported no blood type distribution

  19. [Biological markers of alcoholism].

    PubMed

    Marcos Martín, M; Pastor Encinas, I; Laso Guzmán, F J

    2005-09-01

    Diagnosis of alcoholism is very important, given its high prevalence and possibility of influencing the disease course. For this reason, the so-called biological markers of alcoholism are useful. These are analytic parameters that alter in the presence of excessive alcohol consumption. The two most relevant markers are the gamma-glutamyltranspeptidase and carbohydrate deficient transferrin. With this clinical comment, we aim to contribute to the knowledge of these tests and promote its use in the clinical practice.

  20. Classification of tumor markers.

    PubMed

    Suresh, M R

    1996-01-01

    Since the discovery of the first tumor markers more than a century ago (Bence-Jones proteins), a vast array of molecules have been described as being associated with cancer. These are generally naturally occurring biomolecules with the exception of neo-antigens expressed in certain tumors induced by viruses. Tumor markers can be broadly classified into tumor specific antigens and tumor-associated markers. Most tumor markers were often heralded as highly tumor specific but subsequent studies demonstrated their presence in normal tissues of the adult or in various stages of ontogeny. As a result, very few tumor-specific antigens can be recognized. The idiotypes of immunoglobulins of B cell tumors and certain neo-antigens of virus induced tumors are two examples that are strictly tumor specific. The vast majority of tumor markers are in reality tumor-associated antigens and can be classified into two types based on their size. The low-molecular weight tumor markers (approximately < 1000 Daltons) include some nucleosides, lipid associated sialic acid, polyamines, pseudouridine, pigment derivatives, and other metabolites. The macromolecular tumor antigens are the most important sub-type useful in the clinical management of cancer patients. The large cancer antigens are either enzymes, growth factors, hormones, receptors, biological response modifiers, oncogenes and their products, or glycoconjugates which include glycoproteins and glycolipids. Collectively all the commercial tumor marker assays available to the oncologist for cancer patient management amount to an annual sales of > $1 billion world wide. The demonstrated clinical usefulness and commercial success of tumor markers have continued to fuel exciting research into the discovery and novel uses of new analytes.

  1. A single marker choice strategy in simultaneous characterization and quantification of multiple components by rapid resolution liquid chromatography coupled with triple quadrupole tandem mass spectrometry (RRLC-QqQ-MS).

    PubMed

    Ning, Zhangchi; Liu, Zhenli; Song, Zhiqian; Zhao, Siyu; Dong, Yunzhuo; Zeng, Honglian; Shu, Yisong; Lu, Cheng; Liu, Yuanyan; Lu, Aiping

    2016-05-30

    Single standard to determine multi-components (SSDMC) method has been accepted as an efficient technique for the quality control of Traditional Chinese medicines (TCMs), especially for overcoming the shortage of reference standards. HPLC-UV methods have been applied to establish SSDMC method for quantitative analysis in several plant medicines and Chinese patent medicines, however, no LC-MS methods have been used. The purpose of this study is to put forward an improved strategy for the choice of single marker in SSDMC using rapid resolution liquid chromatography coupled with triple quadrupole tandem mass spectrometry (RRLC-QqQ-MS). Five different Panax genus plants, recorded in the Chinese Pharmacopeia 2015 edition, were used as research subjects. An improved SSDMC strategy for simultaneous characterization and determination of 18 bioactive saponins in five Panax plants was put forward, and which was validated to be more superior. Then, it was fully investigated with respect to linearity, LODs, LOQs, precision and accuracy. Coupling with multivariate statistical analysis, the established and validated SSDMC strategy could be successively used in discrimination of the five Panax genus plants.

  2. Clinical laboratory data: acquire, analyze, communicate, liberate.

    PubMed

    Azzazy, Hassan M E; Elbehery, Ali H A

    2015-01-01

    The availability of portable healthcare devices, which can acquire and transmit medical data to remote experts would dramatically affect healthcare in areas with poor infrastructure. Smartphones, which feature touchscreen computer capabilities and sophisticated cameras, have become widely available with over billion units shipped in 2013. In the clinical laboratory, smartphones have recently brought the capabilities of key instruments such as spectrophotometers, fluorescence analyzers and microscopes into the palm of the hand. Several research groups have developed sensitive and low-cost smartphone-based diagnostic assay prototypes for testing cholesterol, albumin, vitamin D, tumor markers, and the detection of infectious agents. This review covers the use of smartphones to acquire, analyze, communicate, and liberate clinical laboratory data. Smartphones promise to dramatically improve the quality and quantity of healthcare offered in resource-limited areas.

  3. Tumour markers in diagnosis and management.

    PubMed

    Warnes, T W; Smith, A

    1987-01-01

    The 20-year period since the discovery of AFP by Abelev has seen the introduction of a wide range of new tumour markers and it is now clear that PLC is biologically heterogeneous. Hepatoblastomas, fibrolamellar carcinomas, hepatocellular carcinomas and cholangiocarcinomas may secrete a variety of distinctive markers which are predominantly glycoproteins, and may resemble those found in placenta or fetal liver. Diagnostically, AFP remains the best marker for HCC, both in sensitivity and specificity; it is known to consist of isoforms. In patients with elevated serum AFP and filling defects on liver scan, Con A reactive AFP may differentiate PLC from hepatic metastases, whilst fucosylated AFP may distinguish PLC from benign disorders when AFP is non-diagnostically elevated. With this recognition of tumour heterogeneity the value of a multiple-marker approach has become apparent. The measurement of vitamin B12 binding protein and neurotensin should lead to the detection of most patients with the fibrolamellar variant of HCC and many of these should be resectable. In patients with normal serum AFP levels, HCC-associated GGTP is of major value whilst in low-incidence areas for HCC, patients should also be screened for H-ALP; using a multiple marker approach in high-risk groups, 90% of clinically diagnosed hepatocellular carcinomas are serologically positive. The Chinese and Alaskan studies, in which small, potentially resectable tumours were detected, suggest that it is now possible to achieve 5-year survival figures of up to 60% in HCC patients detected by screening. The value of such a strategy in low-incidence countries is currently under study. In patient monitoring, as in diagnosis, AFP remains the outstanding marker. In AFP-negative patients, other markers including vitamin B12-binding protein, neurotensin, HCC-specific isoenzymes, des-gamma-carboxy-prothrombin and alpha-fucosidase, are of undoubted diagnostic value, but their value as indicants of disease

  4. L-split marker for augmented reality in aircraft assembly

    NASA Astrophysics Data System (ADS)

    Han, Pengfei; Zhao, Gang

    2016-04-01

    In order to improve the performance of conventional square markers widely used by marker-based augmented reality systems in aircraft assembly environments, an L-split marker is proposed. Every marker consists of four separate L-shaped parts and each of them contains partial information about the marker. Geometric features of the L-shape, which are more discriminate than the symmetrical square shape adopted by conventional markers, are used to detect proposed markers from the camera images effectively. The marker is split into four separate parts in order to improve the robustness to occlusion and curvature to some extent. The registration process can be successfully completed as long as three parts are detected (up to about 80% of the area could be occluded). Moreover, when we attach the marker on nonplanar surfaces, the curvature status of the marker can be roughly analyzed with every part's normal direction, which can be obtained since their six corners have been explicitly determined in the previous detection process. And based on the marker design, new detection and recognition algorithms are proposed and detailed. The experimental results show that the marker and the algorithms are effective.

  5. Should "Multiple Imputations" Be Treated as "Multiple Indicators"?

    ERIC Educational Resources Information Center

    Mislevy, Robert J.

    1993-01-01

    Multiple imputations for latent variables are constructed so that analyses treating them as true variables have the correct expectations for population characteristics. Analyzing multiple imputations in accordance with their construction yields correct estimates of population characteristics, whereas analyzing them as multiple indicators generally…

  6. A Meta-Regression Method for Studying Etiological Heterogeneity Across Disease Subtypes Classified by Multiple Biomarkers

    PubMed Central

    Wang, Molin; Kuchiba, Aya; Ogino, Shuji

    2015-01-01

    In interdisciplinary biomedical, epidemiologic, and population research, it is increasingly necessary to consider pathogenesis and inherent heterogeneity of any given health condition and outcome. As the unique disease principle implies, no single biomarker can perfectly define disease subtypes. The complex nature of molecular pathology and biology necessitates biostatistical methodologies to simultaneously analyze multiple biomarkers and subtypes. To analyze and test for heterogeneity hypotheses across subtypes defined by multiple categorical and/or ordinal markers, we developed a meta-regression method that can utilize existing statistical software for mixed-model analysis. This method can be used to assess whether the exposure-subtype associations are different across subtypes defined by 1 marker while controlling for other markers and to evaluate whether the difference in exposure-subtype association across subtypes defined by 1 marker depends on any other markers. To illustrate this method in molecular pathological epidemiology research, we examined the associations between smoking status and colorectal cancer subtypes defined by 3 correlated tumor molecular characteristics (CpG island methylator phenotype, microsatellite instability, and the B-Raf protooncogene, serine/threonine kinase (BRAF), mutation) in the Nurses' Health Study (1980–2010) and the Health Professionals Follow-up Study (1986–2010). This method can be widely useful as molecular diagnostics and genomic technologies become routine in clinical medicine and public health. PMID:26116215

  7. Carbohydrate Markers in Colon Carcinoma

    PubMed Central

    Szajda, Sławomir Dariusz; Jankowska, Anna; Zwierz, Krzysztof

    2008-01-01

    Spontaneously mutated multiple oncogenes and/or tumor suppressor genes in colon epithelial cell and its progeny, may cause proliferation out of control and create benign colon neoplasm (colon polyp). If additional mutations involve genes responsible for cell adhesion and movement, aberrant epithelial cells may become malignant (colon cancer) and invade surrounding and remote tissues, creating secondary tumors called metastases. Incidence of colorectal cancer dramatically increases at 50–65 year of age. In Europe in 2006 colorectal cancer consisted 12.9% of all cancers and caused 207 400 deaths. To laboratory detection and monitoring of colon cancer are used tumor markers. Tumor markers are substances produced by the body in response to cancer, or by cancer tissue itself. Glycoconjugate markers for colon cancer include aberrant: mucins covering the surface of the colon epithelial cells, cadherins, selectins and Ig –like adhesion molecules mediating cell-cell adhesion, integrins and integral membrane proteoglycans responsible for adhesion of colon epithelial cells to extracellular matrix, glycoconjugate components of ECM, as well as lysosomal membrane glycoproteins and exoglycosidases. Detection of colon cancer at early non malignant stage is crucial in its prevention and eradication. As colon cancer is the effect of accumulation many somatic mutations in oncogens, supressors, mismatch repair genes and many genes responsible for posttranslational modifications of proteins, multidirectional approach should be applied for its detection. A glycobiological approach to diagnosis and treatment of colorectal cancer should be directed to detection changes in glycosylation accompanying every step of colon cancer progression, and correlation between changes in glycosylation and tumor progression. PMID:19126967

  8. Carbohydrate markers in colon carcinoma.

    PubMed

    Szajda, Sławomir Dariusz; Jankowska, Anna; Zwierz, Krzysztof

    2008-01-01

    Spontaneously mutated multiple oncogenes and/or tumor suppressor genes in colon epithelial cell and its progeny, may cause proliferation out of control and create benign colon neoplasm (colon polyp). If additional mutations involve genes responsible for cell adhesion and movement, aberrant epithelial cells may become malignant (colon cancer) and invade surrounding and remote tissues, creating secondary tumors called metastases. Incidence of colorectal cancer dramatically increases at 50-65 year of age. In Europe in 2006 colorectal cancer consisted 12.9% of all cancers and caused 207,400 deaths. To laboratory detection and monitoring of colon cancer are used tumor markers. Tumor markers are substances produced by the body in response to cancer, or by cancer tissue itself. Glycoconjugate markers for colon cancer include aberrant: mucins covering the surface of the colon epithelial cells, cadherins, selectins and Ig-like adhesion molecules mediating cell-cell adhesion, integrins and integral membrane proteoglycans responsible for adhesion of colon epithelial cells to extracellular matrix, glycoconjugate components of ECM, as well as lysosomal membrane glycoproteins and exoglycosidases. Detection of colon cancer at early non malignant stage is crucial in its prevention and eradication. As colon cancer is the effect of accumulation many somatic mutations in oncogens, supressors, mismatch repair genes and many genes responsible for posttranslational modifications of proteins, multidirectional approach should be applied for its detection. A glycobiological approach to diagnosis and treatment of colorectal cancer should be directed to detection changes in glycosylation accompanying every step of colon cancer progression, and correlation between changes in glycosylation and tumor progression.

  9. Evaluation of Tumor Shape Variability in Head-and-Neck Cancer Patients Over the Course of Radiation Therapy Using Implanted Gold Markers

    SciTech Connect

    Hamming-Vrieze, Olga; Kranen, Simon Robert van; Beek, Suzanne van; Heemsbergen, Wilma; Herk, Marcel van; Brekel, Michiel Wilhelmus Maria van den; Sonke, Jan-Jakob; Rasch, Coenraad Robert Nico

    2012-10-01

    Purpose: This study quantifies tumor shape variability in head-and-neck cancer patients during radiation therapy using implanted markers. Methods and Materials: Twenty-seven patients with oropharyngeal tumors treated with (chemo)radiation were included. Helical gold markers (0.35 Multiplication-Sign 2 mm, 3-10/patient, average 6) were implanted around the tumor. Markers were identified on planning computed tomography (CT) and daily cone beam CT (CBCT). After bony anatomy registration, the daily vector length on CBCT in reference to the planning CT and daily marker movement perpendicular to the gross tumor volume (GTV) surface at planning CT (d{sub normal}) of each marker were analyzed. Time trends were assessed with linear regression of the {sub markers}. In 2 patients, 2 markers were implanted in normal tissue to evaluate migration by measuring intermarker distances. Results: Marker implantation was feasible without complications. Three-dimensional vectors (4827 measurements, mean 0.23 cm, interquartile ratio 0.24 cm) were highest in base of tongue sublocalization (P<.001) and bulky tumors (vectors exceeded 0.5 cm in 5.7% [0-20 mL], 12.0% [21-40 mL], and 21.7% [{>=}41 mL], respectively [P<.001] of measurements). The measured inward time trend in 11/27 patients correlated with the visual observed marker pattern. In patients with an outward trend (5/27) or no trend (11/27), visual observation showed predominantly an inhomogeneous pattern. Remarkably, in 6 patients, outward marker movement was observed in the posterior pharyngeal wall. The difference in distance between normal tissue markers (1 SD) was 0.05-0.06 cm without time trend, indicating that implanted markers did not migrate. Conclusions: During head-and-neck radiation therapy, normal tissue markers remained stable. Changes in position of tumor markers depended on sublocalization and tumor volume. Large differences in marker patterns between patients as well as within patients were observed

  10. Markers of erectile dysfunction

    PubMed Central

    Davies, Kelvin P.; Melman, Arnold

    2008-01-01

    With the development and marketing of oral pharmacotherapy that is both noninvasive and successful in treating erectile dysfunction (ED), the quest to identify markers of organic ED lost ground. Indeed, the multi-factorial nature of ED may have led many researchers to conclude that searching for a universal marker of ED was futile. However, the realization that ED is strongly correlated with the overall health of men, and may act as a predictor for the development of cardiovascular disease (CVD) and diabetes, has stimulated interest in identifying genes that can distinguish organic ED. In addition, the potential ability to suggest to the patient that ED is reversible (i.e., psychogenic) with a simple test would be of significance to both the physician and patient, as well as for reimbursement issues for therapy by insurance companies. Such a marker may also act as a non-subjective measure of the degree of ED and the efficacy of treatment. This review discusses the importance of identifying such markers and recent work identifying potential markers in human patients. PMID:19468461

  11. Fluid markers of traumatic brain injury.

    PubMed

    Zetterberg, Henrik; Blennow, Kaj

    2015-05-01

    Traumatic brain injury (TBI) occurs when an external force traumatically injures the brain. Whereas severe TBI can be diagnosed using a combination of clinical signs and standard neuroimaging techniques, mild TBI (also called concussion) is more difficult to detect. This is where fluid markers of injury to different cell types and subcellular compartments in the central nervous system come into play. These markers are often proteins, peptides or other molecules with selective or high expression in the brain, which can be measured in the cerebrospinal fluid or blood as they leak out or get secreted in response to the injury. Here, we review the literature on fluid markers of neuronal, axonal and astroglial injury to diagnose mild TBI and to predict clinical outcome in patients with head trauma. We also discuss chronic traumatic encephalopathy, a progressive neurodegenerative disease in individuals with a history of multiple mild TBIs in a biomarker context. This article is part of a Special Issue entitled 'Traumatic Brain Injury'.

  12. Development of pulse neutron coal analyzer

    NASA Astrophysics Data System (ADS)

    Jing, Shi-wie; Gu, De-shan; Qiao, Shuang; Liu, Yu-ren; Liu, Lin-mao; Shi-wei, Jing

    2005-04-01

    This article introduced the development of pulsed neutron coal analyzer by pulse fast-thermal neutron analysis technology in the Radiation Technology Institute of Northeast Normal University. The 14MeV pulse neutron generator and bismuth germanate detector and 4096 multichannel analyzer were applied in this system. The multiple linear regression method employed to process data solved the interferential problem of multiple elements. The prototype (model MZ-MKFY) had been applied in Changshan and Jilin power plant for about a year. The results of measuring the main parameters of coal such as low caloric power, whole total water, ash content, volatile content, and sulfur content, with precision acceptable to the coal industry, are presented.

  13. SAM: a system for iteratively building marker maps.

    PubMed

    Soderlund, C; Dunham, I

    1995-12-01

    SAM (system for assembling markers) is a system which supports man-machine problem solving for iteratively ordering a set of markers. SAM aids the user in partially ordering a set of markers based on incomplete and uncertain data. As data is added and modified, SAM aids the user in updating the previously assembled maps. The input is a file of clones and for each clone, a list of the markers contained within it. The objective is to order the set of markers such that the markers contained in each clone are consecutive. The user directs the map building by selecting functions to assemble a region of markers, order the clones to fit the order of the markers and position new markers within an ordered set of markers. The user can edit the input data, edit the assembled map and add clones to the map based on their marker content. The results are displayed graphically and can be saved in a solution file. Based on the partial map, the user designs new experiments or edits the existing data to fill gaps and resolve ambiguities. When a previously assembled map is loaded into SAM, it is automatically updated with the new or altered data. SAM treats all markers as points, but has special features for multiple copy and long markers so that they can be used in the map building process. This system has supported the building of a YAC map of human chromosome 22 at the Sanger Centre, where use of Alu-PCR product markers is a major component in determining clone overlap and where we have an on-going effort to accumulate data from various sources. SAM is also being used at various other laboratories.

  14. Analyzing Association Mapping in Pedigree-Based GWAS Using a Penalized Multitrait Mixed Model.

    PubMed

    Liu, Jin; Yang, Can; Shi, Xingjie; Li, Cong; Huang, Jian; Zhao, Hongyu; Ma, Shuangge

    2016-07-01

    Genome-wide association studies (GWAS) have led to the identification of many genetic variants associated with complex diseases in the past 10 years. Penalization methods, with significant numerical and statistical advantages, have been extensively adopted in analyzing GWAS. This study has been partly motivated by the analysis of Genetic Analysis Workshop (GAW) 18 data, which have two notable characteristics. First, the subjects are from a small number of pedigrees and hence related. Second, for each subject, multiple correlated traits have been measured. Most of the existing penalization methods assume independence between subjects and traits and can be suboptimal. There are a few methods in the literature based on mixed modeling that can accommodate correlations. However, they cannot fully accommodate the two types of correlations while conducting effective marker selection. In this study, we develop a penalized multitrait mixed modeling approach. It accommodates the two different types of correlations and includes several existing methods as special cases. Effective penalization is adopted for marker selection. Simulation demonstrates its satisfactory performance. The GAW 18 data are analyzed using the proposed method. © 2016 WILEY PERIODICALS, INC.

  15. Predicting Markers of Adulthood among Adolescent Mothers

    PubMed Central

    Lee, Jungeun O.; Lohr, Mary Jane

    2010-01-01

    This prospective longitudinal study examines the antecedents of adolescent mothers' transition into adulthood and their attainment of multiple adult statuses in their early 30s in a nonclinical sample. The distribution, timing, and impact of factors in adolescence (education, employment, marriage, economic status, criminal involvement, and others) are shown relative to their impact on the transition into adulthood and attainment of typical markers of adulthood (employment, economic status, marriage, postsecondary education, and family formation). Descriptive data of demographic variables for adolescent mothers are reported from birth of child at average age 16 through 16 years postpartum at average age 32. Logistic regression results indicate that of all the factors examined in adolescence, on-time graduation from high school or receipt of a GED (by age 19) influenced the attainment of multiple markers of adulthood. Implications for intervention and policy with regard to completion of basic education are discussed. PMID:24511218

  16. Multiple sporadic colorectal cancers display a unique methylation phenotype.

    PubMed

    Gonzalo, Victoria; Lozano, Juan Jose; Alonso-Espinaco, Virginia; Moreira, Leticia; Muñoz, Jenifer; Pellisé, Maria; Castellví-Bel, Sergi; Bessa, Xavier; Andreu, Montserrat; Xicola, Rosa M; Llor, Xavier; Ruiz-Ponte, Clara; Carracedo, Angel; Jover, Rodrigo; Castells, Antoni; Balaguer, Francesc

    2014-01-01

    Epigenetics are thought to play a major role in the carcinogenesis of multiple sporadic colorectal cancers (CRC). Previous studies have suggested concordant DNA hypermethylation between tumor pairs. However, only a few methylation markers have been analyzed. This study was aimed at describing the epigenetic signature of multiple CRC using a genome-scale DNA methylation profiling. We analyzed 12 patients with synchronous CRC and 29 age-, sex-, and tumor location-paired patients with solitary tumors from the EPICOLON II cohort. DNA methylation profiling was performed using the Illumina Infinium HM27 DNA methylation assay. The most significant results were validated by Methylight. Tumors samples were also analyzed for the CpG Island Methylator Phenotype (CIMP); KRAS and BRAF mutations and mismatch repair deficiency status. Functional annotation clustering was performed. We identified 102 CpG sites that showed significant DNA hypermethylation in multiple tumors with respect to the solitary counterparts (difference in β value ≥0.1). Methylight assays validated the results for 4 selected genes (p = 0.0002). Eight out of 12(66.6%) multiple tumors were classified as CIMP-high, as compared to 5 out of 29(17.2%) solitary tumors (p = 0.004). Interestingly, 76 out of the 102 (74.5%) hypermethylated CpG sites found in multiple tumors were also seen in CIMP-high tumors. Functional analysis of hypermethylated genes found in multiple tumors showed enrichment of genes involved in different tumorigenic functions. In conclusion, multiple CRC are associated with a distinct methylation phenotype, with a close association between tumor multiplicity and CIMP-high. Our results may be important to unravel the underlying mechanism of tumor multiplicity.

  17. Multiple Sporadic Colorectal Cancers Display a Unique Methylation Phenotype

    PubMed Central

    Gonzalo, Victoria; Lozano, Juan Jose; Alonso-Espinaco, Virginia; Moreira, Leticia; Muñoz, Jenifer; Pellisé, Maria; Castellví-Bel, Sergi; Bessa, Xavier; Andreu, Montserrat; Xicola, Rosa M.; Llor, Xavier; Ruiz-Ponte, Clara; Carracedo, Angel; Jover, Rodrigo; Castells, Antoni; Balaguer, Francesc

    2014-01-01

    Epigenetics are thought to play a major role in the carcinogenesis of multiple sporadic colorectal cancers (CRC). Previous studies have suggested concordant DNA hypermethylation between tumor pairs. However, only a few methylation markers have been analyzed. This study was aimed at describing the epigenetic signature of multiple CRC using a genome-scale DNA methylation profiling. We analyzed 12 patients with synchronous CRC and 29 age-, sex-, and tumor location-paired patients with solitary tumors from the EPICOLON II cohort. DNA methylation profiling was performed using the Illumina Infinium HM27 DNA methylation assay. The most significant results were validated by Methylight. Tumors samples were also analyzed for the CpG Island Methylator Phenotype (CIMP); KRAS and BRAF mutations and mismatch repair deficiency status. Functional annotation clustering was performed. We identified 102 CpG sites that showed significant DNA hypermethylation in multiple tumors with respect to the solitary counterparts (difference in β value ≥0.1). Methylight assays validated the results for 4 selected genes (p = 0.0002). Eight out of 12(66.6%) multiple tumors were classified as CIMP-high, as compared to 5 out of 29(17.2%) solitary tumors (p = 0.004). Interestingly, 76 out of the 102 (74.5%) hypermethylated CpG sites found in multiple tumors were also seen in CIMP-high tumors. Functional analysis of hypermethylated genes found in multiple tumors showed enrichment of genes involved in different tumorigenic functions. In conclusion, multiple CRC are associated with a distinct methylation phenotype, with a close association between tumor multiplicity and CIMP-high. Our results may be important to unravel the underlying mechanism of tumor multiplicity. PMID:24643221

  18. Droplet actuator analyzer with cartridge

    NASA Technical Reports Server (NTRS)

    Smith, Gregory F. (Inventor); Sturmer, Ryan A. (Inventor); Paik, Philip Y. (Inventor); Srinivasan, Vijay (Inventor); Pollack, Michael G. (Inventor); Pamula, Vamsee K. (Inventor); Brafford, Keith R. (Inventor); West, Richard M. (Inventor)

    2011-01-01

    A droplet actuator with cartridge is provided. According to one embodiment, a sample analyzer is provided and includes an analyzer unit comprising electronic or optical receiving means, a cartridge comprising self-contained droplet handling capabilities, and a wherein the cartridge is coupled to the analyzer unit by a means which aligns electronic and/or optical outputs from the cartridge with electronic or optical receiving means on the analyzer unit. According to another embodiment, a sample analyzer is provided and includes a sample analyzer comprising a cartridge coupled thereto and a means of electrical interface and/or optical interface between the cartridge and the analyzer, whereby electrical signals and/or optical signals may be transmitted from the cartridge to the analyzer.

  19. Soft Decision Analyzer and Method

    NASA Technical Reports Server (NTRS)

    Steele, Glen F. (Inventor); Lansdowne, Chatwin (Inventor); Zucha, Joan P. (Inventor); Schlesinger, Adam M. (Inventor)

    2015-01-01

    A soft decision analyzer system is operable to interconnect soft decision communication equipment and analyze the operation thereof to detect symbol wise alignment between a test data stream and a reference data stream in a variety of operating conditions.

  20. Soft Decision Analyzer and Method

    NASA Technical Reports Server (NTRS)

    Steele, Glen F. (Inventor); Lansdowne, Chatwin (Inventor); Zucha, Joan P. (Inventor); Schlesinger, Adam M. (Inventor)

    2016-01-01

    A soft decision analyzer system is operable to interconnect soft decision communication equipment and analyze the operation thereof to detect symbol wise alignment between a test data stream and a reference data stream in a variety of operating conditions.

  1. Microsatellite markers for the human nematode parasite Ascaris lumbricoides: development and assessment of utility.

    PubMed

    Criscione, Charles D; Anderson, Joel D; Raby, Kyle; Sudimack, Dan; Subedi, Janardan; Rai, Dev R; Upadhayay, Ram P; Jha, Bharat; Williams-Blangero, Sarah; Anderson, Timothy J C

    2007-06-01

    We describe 35 microsatellite markers from the human parasitic nematode Ascaris lumbricoides. We found 7 sex-linked markers and demonstrate that 26 autosomal loci can be scored reliably. These markers have high genetic variability and provide the tools to address multiple questions concerning the epidemiology, fine-scale genetic structure, host specificity, and mating systems of this parasite.

  2. Discourse Markers in the Spoken Portuguese of Rio de Janeiro.

    ERIC Educational Resources Information Center

    de Olveira e Silva, Giselle M.; de Macedo, Alzira Tavares

    1992-01-01

    A study analyzed four major classes of discourse marker in Brazilian Portuguese: "ne" and other requests for feedback; "ai," a sequential connector; "ah, bom," and other turn initiators; and "assim," a marker of explanation. Distribution in various discourse functions and sociodemographic conditioning, and…

  3. Novel markers of osteogenic and adipogenic differentiation of human bone marrow stromal cells identified using a quantitative proteomics approach.

    PubMed

    Granéli, Cecilia; Thorfve, Anna; Ruetschi, Ulla; Brisby, Helena; Thomsen, Peter; Lindahl, Anders; Karlsson, Camilla

    2014-01-01

    Today, the tool that is most commonly used to evaluate the osteogenic differentiation of bone marrow stromal cells (BMSCs) in vitro is the demonstration of the expression of multiple relevant markers, such as ALP, RUNX2 and OCN. However, as yet, there is no single surface marker or panel of markers which clearly defines human BMSCs (hBMSCs) differentiating towards the osteogenic lineage. The aim of this study was therefore to examine this issue. Stable isotope labeling by amino acids in cell culture (SILAC)-based quantitative proteomics was utilized to investigate differently expressed surface markers in osteogenically differentiated and undifferentiated hBMSCs. Labeled membrane proteins were analyzed by mass spectrometry (MS) and 52 proteins with an expression ratio above 2, between osteogenically differentiated and undifferentiated cells, were identified. Subsequent validation, by flow cytometry and ELISA, of the SILAC expression ratios for a number of these proteins and investigations of the lineage specificity of three candidate markers were performed. The surface markers, CD10 and CD92, demonstrated significantly increased expression in hBMSCs differentiated towards the osteogenic and adipogenic lineages. In addition, there was a slight increase in CD10 expression during chondrogenic differentiation. Furthermore, the expression of the intracellular protein, crystalline-αB (CRYaB), was only significantly increased in osteogenically differentiated hBMSCs and not affected during differentiation towards the chondrogenic or adipogenic lineages. It has been concluded from the present results that CD10 and CD92 are potential markers of osteogenic and adipogenic differentiation and that CRYaB is a potential novel osteogenic marker specifically expressed during the osteogenic differentiation of hBMSCs in vitro.

  4. Frailty Markers and Treatment Decisions in Patients Seen in Oncogeriatric Clinics: Results from the ASRO Pilot Study

    PubMed Central

    de Decker, Laure; Pauly, Vanessa; Rousseau, Frédérique; Bergman, Howard; Molines, Catherine

    2016-01-01

    Background Comprehensive Geriatric Assessment (CGA) is the gold standard to help oncologists select the best cancer treatment for their older patients. Some authors have suggested that the concept of frailty could be a more useful approach in this population. We investigated whether frailty markers are associated with treatment recommendations in an oncogeriatric clinic. Methods This prospective study included 70 years and older patients with solid tumors and referred for an oncogeriatric assessment. The CGA included nine domains: autonomy, comorbidities, medication, cognition, nutrition, mood, neurosensory deficits, falls, and social status. Five frailty markers were assessed (nutrition, physical activity, energy, mobility, and strength). Patients were categorized as Frail (three or more frailty markers), pre-frail (one or two frailty markers), or not-frail (no frailty marker). Treatment recommendations were classified into two categories: standard treatment with and without any changes and supportive/palliative care. Multiple logistic regression models were used to analyze factors associated with treatment recommendations. Results 217 patients, mean age 83 years (± Standard deviation (SD) 5.3), were included. In the univariate analysis, number of frailty markers, grip strength, physical activity, mobility, nutrition, energy, autonomy, depression, Eastern Cooperative Oncology Group Scale of Performance Status (ECOG-PS), and falls were significantly associated with final treatment recommendations. In the multivariate analysis, the number of frailty markers and basic Activities of Daily Living (ADL) were significantly associated with final treatment recommendations (p<0.001 and p = 0.010, respectively). Conclusion Frailty markers are associated with final treatment recommendations in older cancer patients. Longitudinal studies are warranted to better determine their use in a geriatric oncology setting. PMID:26918947

  5. Prognostic factors versus markers of response to treatment versus surrogate endpoints: Three different concepts.

    PubMed

    Sormani, Maria Pia

    2017-03-01

    Multiple sclerosis is a highly heterogeneous disease; the quantitative assessment of disease progression is problematic for many reasons, including the lack of objective methods to measure disability and the long follow-up times needed to detect relevant and stable changes. For these reasons, the importance of prognostic markers, markers of response to treatments and of surrogate endpoints, is crucial in multiple sclerosis research. Aim of this report is to clarify some basic definitions and methodological issues about baseline factors to be considered prognostic markers or markers of response to treatment; to define the dynamic role that variables must have to be considered surrogate markers in relation to specific treatments.

  6. [Correlation of sex hormones and parathyroid hormone with biochemical markers of bone turnover in aged men].

    PubMed

    Xiao, Hai-Ying; Lu, Yan-Hui; Gong, Yan-Ping; Pei, Yu; Cheng, Xiao-Ling; Li, Nan; Fang, Fu-Sheng; Tian, Hui; Li, Chun-Lin

    2014-03-01

    To investigate the correlation of serum sex hormones and parathyroid hormone (PTH) with the biochemical markers of bone turnover in aged men. We collected the laboratory data of 465 men aged 60- 93 (73. 1 +/- 8. 3) years old, who came for routine physical examinations in our hospital. We obtained the levels of serum follicle- stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), testosterone (T), sex hormone binding globulin (SHBG), PTH, 25-hydroxy-vitamin D3 (25(OH) D3), and bone turnover markers C-terminal telopeptide of type I collagen (CTX), osteocalcin (OC) and amino-terminal propeptide of type I procollagen (PINP). We also determined free testosterone (FT) , bioactive testosterone (BT) , testosterone secretion index (TSI) and FT index (FTI), and analyzed the correlation of each index with the biochemical markers of bone turnover. The concentrations of serum FSH, LH, and SHBG increased, while the levels of FT, BT, TSI, FTI, PTH, CTX, OC and PINP decreased with age, especially in those over 80 years old (P <0.05). PTH was positively correlated with CTX, OC and PINP (r =0. 227, 0. 269 and 0. 162, P <0. 01), even after the adjustment for age, while SHBG negatively correlated with OC (r = -0. 100, P <0.05). The bone turnover markers increased with the elevation of the PTH quartiles, with significant differences between the first and the fourth quartile (P <0. 01). Multiple stepwise regression analysis showed that age was correlated inversely with CTX, OC and PINP ( beta = -0. 126, -0. 141 and -0. 122, P <0.05) , PTH positively with the three markers (beta = 0. 196, 0.279 and 0.189; P <0. 001), and SHBG negatively with OC ( beta = -0. 100, P <0.05) . Aging is the fundamental cause of reduced bone turnover in aged men. The levels serum PTH and SHBG are significantly associated with the biochemical markers of bone turnover.

  7. The Swift Turbidity Marker

    ERIC Educational Resources Information Center

    Omar, Ahmad Fairuz; MatJafri, Mohd Zubir

    2011-01-01

    The Swift Turbidity Marker is an optical instrument developed to measure the level of water turbidity. The components and configuration selected for the system are based on common turbidity meter design concepts but use a simplified methodology to produce rapid turbidity measurements. This work is aimed at high school physics students and is the…

  8. The Swift Turbidity Marker

    ERIC Educational Resources Information Center

    Omar, Ahmad Fairuz; MatJafri, Mohd Zubir

    2011-01-01

    The Swift Turbidity Marker is an optical instrument developed to measure the level of water turbidity. The components and configuration selected for the system are based on common turbidity meter design concepts but use a simplified methodology to produce rapid turbidity measurements. This work is aimed at high school physics students and is the…

  9. Stennis historical marker

    NASA Image and Video Library

    2011-10-25

    Stennis Space Center Director Patrick Scheuermann (second from left) stands at the historical marker erected by the state of Mississippi in honor of the 50th anniversary of the NASA facility. Joining Scheuermann are: (l to r) Ron Magee, Al Watkins, Tish Williams and Ken P'Pool.

  10. Contribution of Frailty Markers in Explaining Differences Among Individuals in Five Samples of Older Persons

    PubMed Central

    Sourial, Nadia; Karunananthan, Sathya; Wolfson, Christina; Guralnik, Jack; Payette, Hélène; Gutierrez-Robledo, Luis; Deeg, Dorly J. H.; Fletcher, John D.; Puts, Maria T. E.; Zhu, Bin; Béland, François

    2012-01-01

    Background. There has been little research on the relative importance of frailty markers. The objective was to investigate the association among seven frailty domains (nutrition, physical activity, mobility, strength, energy, cognition, and mood) and their relative contribution in explaining differences among individuals in five samples of older persons. Methods. Data from five studies of aging were analyzed using multiple correspondence analysis. Aggregation of frailty markers was evaluated using graphical output. Decomposition of variability was used to assess the relative contribution of each marker in each sample. Results were combined across the samples to assess the average contribution. Results. Frailty markers were found to consistently aggregate in each sample, suggesting a possible underlying construct. Physical strength had the highest contribution on average in explaining differences among individuals. Mobility and energy also had large contributions. Nutrition and cognition had the smallest contributions. Conclusions. Our results provide further evidence supporting the notion that frailty domains may belong to a common construct. Physical strength may be the most important discriminating characteristic. PMID:22459619

  11. Source apportionment of particulate matter in the US and associations with lung inflammatory markers

    SciTech Connect

    Duvall, R.M.; Norris, G.A.; Dailey, L.A.; Burke, J.M.; McGee, J.K.; Gilmour, M.I.; Gordon, T.; Devlin, R.B.

    2008-07-01

    Size-fractionated particulate matter (PM) samples were collected from six U.S. cities and chemically analyzed as part of the Multiple Air Pollutant Study. Particles were administered to cultured lung cells and the production of three different proinflammatory markers was measured to explore the association between the health effect markers and PM. Ultrafine, fine, and coarse PM samples were collected between December 2003 and May 2004 over a 4-wk period in each city. Filters were pooled for each city and the PM samples were extracted then analyzed for trace metals, ions, and elemental carbon. Particle extracts were applied to cultured human primary airway epithelial cells, and the secreted levels of interleukin-8 (IL-8), heme oxygenase-1, and cyclooxygenase-2 were measured 1 and 24 h following exposure. Fine PM sources were quantified by the chemical mass balance (CMB) model. The relationship between toxicological measures, PM sources, and individual species were evaluated using linear regression. Ultrafine and fine PM mass were associated with increases in IL-8 (r{sup 2} = .80 for ultrafine and r{sup 2} = .52 for fine). Sources of fine PM and their relative contributions varied across the sampling sites and a strong linear association was observed between IL-8 and secondary sulfate from coal combustion (r{sup 2} = .79). Ultrafine vanadium, lead, copper, and sulfate were also associated with increases in IL-8. Increases in inflammatory markers were not observed for coarse PM mass and source markers. These findings suggest that certain PM size fractions and sources are associated with markers of lung injury or inflammation.

  12. Development of a Fast Ion Energy Analyzer

    NASA Astrophysics Data System (ADS)

    Young, W. C.; Bellan, P. M.

    2003-10-01

    In an effort to measure the ion energy spectra of short duration plasmas, two different analyzers are being compared for usability on short time scales. A traditional energy analyzer, the retarding field energy analyzer (RFEA), is being compared to a design using an electric field to deflect ions onto multiple collectors. The use of multiple collectors allows for simultaneous measurement of several energies overcoming the major limitation of the RFEA is measuring only a single energy per plasma shot. The tradeoff is that the energy resolution of the new design is limited by the number of collectors. These methods are being tested on both a single energy electron gun and also on a spheromak with a plasma duration of 20-30 μs and ion temperature of 20 eV. Both designs have been demonstrated to work under simplified conditions using an electron gun. Currently the RFEA is being tested on the spheromak and efforts are being made to increase the resolution and lower the noise of the new analyzer.

  13. Molecular markers based on LTR retrotransposons BARE-1 and Jeli uncover different strata of evolutionary relationships in diploid wheats.

    PubMed

    Konovalov, Fedor A; Goncharov, Nikolay P; Goryunova, Svetlana; Shaturova, Aleksandra; Proshlyakova, Tatyana; Kudryavtsev, Alexander

    2010-06-01

    Molecular markers based on retrotransposon insertions are widely used for various applications including phylogenetic analysis. Multiple cases were described where retrotransposon-based markers, namely sequence-specific amplification polymorphism (SSAP), were superior to other marker types in resolving the phylogenetic relationships due to their higher variability and informativeness. However, the patterns of evolutionary relationships revealed by SSAP may be dependent on the underlying retrotransposon activity in different periods of time. Hence, the proper choice of retrotransposon family is essential for obtaining significant results. We compared the phylogenetic trees for a diverse set of diploid A-genome wheat species (Triticum boeoticum, T. urartu and T. monococcum) based on two unrelated retrotransposon families, BARE-1 and Jeli. BARE-1 belongs to Copia class and has a uniform distribution between common wheat (T. aestivum) genomes of different origin (A, B and D), indicating similar activity in the respective diploid genome donors. Gypsy-class family Jeli was found by us to be an A-genome retrotransposon with >70% copies residing in A genome of hexaploid common wheat, suggesting a burst of transposition in the history of A-genome progenitors. The results indicate that a higher Jeli transpositional activity was associated with T. urartu versus T. boeoticum speciation, while BARE-1 produced more polymorphic insertions during subsequent intraspecific diversification; as an outcome, each retrotransposon provides more informative markers at the corresponding level of phylogenetic relationships. We conclude that multiple retroelement families should be analyzed for an image of evolutionary relationships to be solid and comprehensive.

  14. Interpolation Errors in Spectrum Analyzers

    NASA Technical Reports Server (NTRS)

    Martin, J. L.

    1996-01-01

    To obtain the proper measurement amplitude with a spectrum analyzer, the correct frequency-dependent transducer factor must be added to the voltage measured by the transducer. This report examines how entering transducer factors into a spectrum analyzer can cause significant errors in field amplitude due to the misunderstanding of the analyzer's interpolation methods. It also discusses how to reduce these errors to obtain a more accurate field amplitude reading.

  15. Immunological effects of methylprednisolone pulse treatment in progressive multiple sclerosis.

    PubMed

    Ratzer, R; Romme Christensen, J; Romme Nielsen, B; Sørensen, P S; Börnsen, L; Sellebjerg, F

    2014-11-15

    To investigate the effect of monthly oral methylprednisolone pulse treatment in progressive MS. 30 progressive MS patients were treated with oral methylprednisolone every month. Peripheral blood mononuclear cells were analyzed by flow cytometry. Out of 102 leukocyte phenotypes investigated, 25 changed at nominal significance from baseline to week 12 (p<0.05). After correction for multiple comparisons, we found 5 subpopulations that changed compared to baseline. No pattern were suggesting modulation of Th17 or TFH cells. Methylprednisolone pulse treatment has some effects on circulating immune cells but does not modulate markers of Th17 and TFH cell activity in progressive MS. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Consistency of bone turnover marker and calcium responses to parathyroid hormone (1-84) therapy in postmenopausal osteoporosis.

    PubMed

    Schafer, Anne L; Palermo, Lisa; Bauer, Douglas C; Bilezikian, John P; Sellmeyer, Deborah E; Black, Dennis M

    2011-01-01

    We investigated whether those who experience the greatest increases in bone turnover in response to parathyroid hormone (PTH) therapy are the same as those who experience elevations in calcium levels. Baseline and follow-up procollagen type I N propeptide (PINP), bone-specific alkaline phosphatase (BAP), C-terminal telopeptide (CTX), and serum and urinary calcium levels were analyzed post hoc from the 119 postmenopausal women with osteoporosis randomized to PTH(1-84) in the Parathyroid Hormone and Alendronate trial. Short-term changes in the markers of bone turnover were highly correlated with one another (r=0.57-0.87, p<0.001). In contrast, change in serum calcium correlated only modestly with changes in markers of formation (r=0.22-0.30, p≤0.02) and did not correlate significantly with change in CTX (r=0.13, p=0.18). Participants who experienced hypercalcemia experienced greater 3-mo changes in BAP than those who did not (78% vs. 42% increase in BAP, p=0.04), with similar trends for PINP and CTX. In conclusion, the use of 1 marker of bone turnover, rather than multiple markers, may be sufficient to assess biochemical response to PTH(1-84). The relationship between bone turnover marker and calcium responses to PTH(1-84) is modest and does not suggest a profound, broadly heightened responsiveness of certain individuals to therapy.

  17. Adverse Effects of Pesticides Residues on Biochemical Markers in Pakistani Tobacco Farmers

    PubMed Central

    Khan, Dilshad A; Bhatti, Mahwish M; Khan, Farooq A; Naqvi, Syed T; Karam, A

    2008-01-01

    Tobacco is an important cash crop of Pakistan and tremendous amount of irrational pesticides are being used to control insect growth. The frequency of plasma pesticide residues above acceptable daily intake (ADI) and its correlation with biochemical markers for assessment of adverse health effects in the tobacco farmers at district Sawabi, Pakistan was determined. Total 109 adult males consisting of 55 tobacco farmers exposed to pesticides and 54 controls were included. Pesticides residues in blood were analyzed on HPLC and GC-NPD. Plasma butyrylcholinesterase (BChE) was analyzed by Ellman's method. Biochemical markers including serum calcium, phosphorus, urea, creatinine, bilirubin and liver enzymes were measured on Selectra-E auto analyzer. The tobacco farmers had multiple pesticides residues above ADI in their blood consisting of 35 (63%) methomyl; 31 (56%) thiodicarb; 34(62%) cypermethrin; 27 (49%) Imidacloprid; 18 (32%) Methamidophos and 15 (27%) endosulfan. BChE activity was significantly decreased in the pesticides exposed farmers as compared to controls (P<0.001). Plasma biochemical markers including ALT, AST, CK, LDH and phosphate were significantly raised in the pesticides exposed farmers as compared to control group (P<0.001). Total pesticides residues revealed a significant positive correlation with AST (r=0.42), LDH(r= 0.47), ALT (r=0.20) and phosphorus (r=0.51). Excessive exposure to pesticide caused cytotoxic changes in the hepatic and renal biochemical markers which were positively correlated with pesticide residue. Hence these biomarkers might be used in addition to BChE activity for monitoring of adverse effects of pesticides on the health of farm workers. PMID:19079663

  18. Lipoprotein marker for hypertriglyceridemia

    DOEpatents

    Cubicciotti, Roger S.; Karu, Alexander E.; Krauss, Ronald M.

    1986-01-01

    Methods and compositions are provided for the detection of a particular low density lipoprotein which has been found to be a marker for patients suffering from type IV hypertriglyceridemia. A monoclonal antibody capable of specifically binding to a characteristic epitopic site on this LDL subspecies can be utilized in a wide variety of immunoassays. Hybridoma cell line SPL.IVA5A1 was deposited at the American Type Culture Collection on Ma