WorldWideScience

Sample records for target factor analysis

  1. [A new calibration transfer method based on target factor analysis].

    Science.gov (United States)

    Wang, Yan-bin; Yuan, Hong-fu; Lu, Wan-zhen

    2005-03-01

    A new calibration transfer method based on target factor analysis is proposed.The performance of the new method compared with the piecewise direct standardization method. This method was applied to two data sets, of which one is a simulation data set, and the other is an NIR data set composed of benzene, toluene, xylene and isooctane. The results obtained with this new method are at least as well as those obtained by PDS with the biggest improvement occurring when the spectra have some non-linear responses.

  2. Simultaneous Determination of Aspirin, Salicylamide, and Caffeine in Pain Relievers by Target Factor Analysis

    Science.gov (United States)

    Msimanga, Huggins Z.; Charles, Melissa J.; Martin, Nea W.

    1997-09-01

    A factor analysis-based experiment for the undergraduate instrumental analysis labs is reported. Target factor analysis (TFA) is investigated as an option to the use of high-performance liquid chromatography (HPLC) in the analysis of a pain reliever sample containing aspirin, caffeine, and salicylamide.

  3. Local examination of skin diffusion using FTIR spectroscopic imaging and multivariate target factor analysis.

    Science.gov (United States)

    Tetteh, J; Mader, K T; Andanson, J-M; McAuley, W J; Lane, M E; Hadgraft, J; Kazarian, S G; Mitchell, J C

    2009-05-29

    In the context of trans-dermal drug delivery it is very important to have mechanistic insight into the barrier function of the skin's stratum corneum and the diffusion mechanisms of topically applied drugs. Currently spectroscopic imaging techniques are evolving which enable a spatial examination of various types of samples in a dynamic way. ATR-FTIR imaging opens up the possibility to monitor spatial diffusion profiles across the stratum corneum of a skin sample. Multivariate data analyses methods based on factor analysis are able to provide insight into the large amount of spectroscopically complex and highly overlapping signals generated. Multivariate target factor analysis was used for spectral resolution and local diffusion profiles with time through stratum corneum. A model drug, 4-cyanophenol in polyethylene glycol 600 and water was studied. Results indicate that the average diffusion profiles between spatially different locations show similar profiles despite the heterogeneous nature of the biological sample and the challenging experimental set-up.

  4. Genome-wide identification of the regulatory targets of a transcription factor using biochemical characterization and computational genomic analysis

    Directory of Open Access Journals (Sweden)

    Jolly Emmitt R

    2005-11-01

    Full Text Available Abstract Background A major challenge in computational genomics is the development of methodologies that allow accurate genome-wide prediction of the regulatory targets of a transcription factor. We present a method for target identification that combines experimental characterization of binding requirements with computational genomic analysis. Results Our method identified potential target genes of the transcription factor Ndt80, a key transcriptional regulator involved in yeast sporulation, using the combined information of binding affinity, positional distribution, and conservation of the binding sites across multiple species. We have also developed a mathematical approach to compute the false positive rate and the total number of targets in the genome based on the multiple selection criteria. Conclusion We have shown that combining biochemical characterization and computational genomic analysis leads to accurate identification of the genome-wide targets of a transcription factor. The method can be extended to other transcription factors and can complement other genomic approaches to transcriptional regulation.

  5. Determination of mineral matter in coal by target transformation factor analysis

    International Nuclear Information System (INIS)

    Roscoe, B.A.; Hopke, P.K.

    1980-01-01

    There is an increasing need to determine the nature of mineral matter in coal. The mineral matter is composed of all inclusions in the coal whether or not they are distinct from the coal. The need for this information is based on the increased use of coal and the problems associated with its use such as boiler tube fouling, air pollution, and coal liquefaction. By utilizing target transformation factor analysis, it is possible to identify the number of mineral phases that may be present in the coal as well as the composition of these mineral phases including major, minor, and trace elements. It is thus possible to determine the mineral phases and reconstruct the mineralogy of the coal sampled such that general characteristics of the mineral phases can be determined. From this information, insight into the formation of the coal can be obtained and better methods of utilizing the coal can be devised

  6. Factor Analysis of Therapist-Identified Treatment Targets in Community-Based Children's Mental Health.

    Science.gov (United States)

    Love, Allison R; Okado, Izumi; Orimoto, Trina E; Mueller, Charles W

    2018-01-01

    The present study used exploratory and confirmatory factor analyses to identify underlying latent factors affecting variation in community therapists' endorsement of treatment targets. As part of a statewide practice management program, therapist completed monthly reports of treatment targets (up to 10 per month) for a sample of youth (n = 790) receiving intensive in-home therapy. Nearly 75 % of youth were diagnosed with multiple co-occurring disorders. Five factors emerged: Disinhibition, Societal Rules Evasion, Social Engagement Deficits, Emotional Distress, and Management of Biodevelopmental Outcomes. Using logistic regression, primary diagnosis predicted therapist selection of Disinhibition and Emotional Distress targets. Client age predicted endorsement of Societal Rules Evasion targets. Practice-to-research implications are discussed.

  7. SUPERPIXEL BASED FACTOR ANALYSIS AND TARGET TRANSFORMATION METHOD FOR MARTIAN MINERALS DETECTION

    Directory of Open Access Journals (Sweden)

    X. Wu

    2018-04-01

    Full Text Available The Factor analysis and target transformation (FATT is an effective method to test for the presence of particular mineral on Martian surface. It has been used both in thermal infrared (Thermal Emission Spectrometer, TES and near-infrared (Compact Reconnaissance Imaging Spectrometer for Mars, CRISM hyperspectral data. FATT derived a set of orthogonal eigenvectors from a mixed system and typically selected first 10 eigenvectors to least square fit the library mineral spectra. However, minerals present only in a limited pixels will be ignored because its weak spectral features compared with full image signatures. Here, we proposed a superpixel based FATT method to detect the mineral distributions on Mars. The simple linear iterative clustering (SLIC algorithm was used to partition the CRISM image into multiple connected image regions with spectral homogeneous to enhance the weak signatures by increasing their proportion in a mixed system. A least square fitting was used in target transformation and performed to each region iteratively. Finally, the distribution of the specific minerals in image was obtained, where fitting residual less than a threshold represent presence and otherwise absence. We validate our method by identifying carbonates in a well analysed CRISM image in Nili Fossae on Mars. Our experimental results indicate that the proposed method work well both in simulated and real data sets.

  8. Discriminant analysis in the presence of interferences: combined application of target factor analysis and a Bayesian soft-classifier.

    Science.gov (United States)

    Rinke, Caitlin N; Williams, Mary R; Brown, Christopher; Baudelet, Matthieu; Richardson, Martin; Sigman, Michael E

    2012-11-13

    A method is described for performing discriminant analysis in the presence of interfering background signal. The method is based on performing target factor analysis on a data set comprised of contributions from analyte(s) and interfering components. A library of data from representative analyte classes is tested for possible contributing factors by performing oblique rotations of the principal factors to obtain the best match, in a least-squares sense, between test and predicted vectors. The degree of match between the test and predicted vectors is measured by the Pearson correlation coefficient, r, and the distribution of r for each class is determined. A Bayesian soft classifier is used to calculate the posterior probability based on the distributions of r for each class, which assist the analyst in assessing the presence of one or more analytes. The method is demonstrated by analyses performed on spectra obtained by laser induced breakdown spectroscopy (LIBS). Single and multiple bullet jacketing transfers to steel and porcelain substrates were analyzed to identify the jacketing materials. Additionally, the metal surrounding bullet holes was analyzed to identify the class of bullet jacketing that passed through a stainless steel plate. Of 36 single sample transfers, the copper jacketed (CJ) and non-jacketed (NJ) class on porcelain had an average posterior probability of the metal deposited on the substrate of 1.0. Metal jacketed (MJ) bullet transfers to steel and porcelain were not detected as successfully. Multiple transfers of CJ/NJ and CJ/MJ on the two substrates resulted in posterior probabilities that reflected the presence of both jacketing materials. The MJ/NJ transfers gave posterior probabilities that reflected the presence of the NJ material, but the MJ component was mistaken for CJ on steel, while non-zero probabilities were obtained for both CJ and MJ on porcelain. Jacketing transfer from a bullet to steel as the projectile passed through the steel

  9. Reduction of interferences in the analysis of Children's Dimetapp using ultraviolet spectroscopy data and target factor analysis

    Science.gov (United States)

    Msimanga, Huggins Z.; Lam, Truong Thach Ho; Latinwo, Nathaniel; Song, Mihyang Kristy; Tavakoli, Newsha

    2018-03-01

    A calibration matrix has been developed and successfully applied to quantify actives in Children's Dimetapp®, a cough mixture whose active components suffer from heavy spectral interference. High-performance liquid chromatography/photodiode array instrument was used to identify the actives and any other UV-detectable excipients that might contribute to interferences. The instrument was also used to obtain reference data on the actives, instead of relying on the manufacturer's claims. Principal component analysis was used during the developmental stages of the calibration matrix to highlight any mismatch between the calibration and sample spectra, making certain that "apples" were not compared with "oranges". The prediction model was finally calculated using target factor analysis and partial least squares regression. In addition to the actives in Children's Dimetapp® (brompheniramine maleate, phenylephrine hydrogen chloride, and dextromethorphan hydrogen bromide), sodium benzoate was identified as the major and FD&C Blue #1, FD&C Red #40, and methyl anthranilate as minor spectral interferences. Model predictions were compared before and after the interferences were included into the calibration matrix. Before including interferences, the following results were obtained: brompheniramine maleate = 481.3 mg L- 1 ± 134% RE; phenylephrine hydrogen chloride = 1041 mg L- 1 ± 107% RE; dextromethorphan hydrogen bromide = 1571 mg L- 1 ± 107% RE, where % RE = percent relative error based on the reference HPLC data. After including interferences, the results were as follows: brompheniramine maleate = 196.3 mg L- 1 ± 4.4% RE; phenylephrine hydrogen chloride = 501.3 mg L- 1 ± 0.10% RE; dextromethorphan hydrogen bromide = 998.7 mg L- 1 ± 1.6% RE as detailed in Table 6.

  10. Ensemble-sensitivity Analysis Based Observation Targeting for Mesoscale Convection Forecasts and Factors Influencing Observation-Impact Prediction

    Science.gov (United States)

    Hill, A.; Weiss, C.; Ancell, B. C.

    2017-12-01

    The basic premise of observation targeting is that additional observations, when gathered and assimilated with a numerical weather prediction (NWP) model, will produce a more accurate forecast related to a specific phenomenon. Ensemble-sensitivity analysis (ESA; Ancell and Hakim 2007; Torn and Hakim 2008) is a tool capable of accurately estimating the proper location of targeted observations in areas that have initial model uncertainty and large error growth, as well as predicting the reduction of forecast variance due to the assimilated observation. ESA relates an ensemble of NWP model forecasts, specifically an ensemble of scalar forecast metrics, linearly to earlier model states. A thorough investigation is presented to determine how different factors of the forecast process are impacting our ability to successfully target new observations for mesoscale convection forecasts. Our primary goals for this work are to determine: (1) If targeted observations hold more positive impact over non-targeted (i.e. randomly chosen) observations; (2) If there are lead-time constraints to targeting for convection; (3) How inflation, localization, and the assimilation filter influence impact prediction and realized results; (4) If there exist differences between targeted observations at the surface versus aloft; and (5) how physics errors and nonlinearity may augment observation impacts.Ten cases of dryline-initiated convection between 2011 to 2013 are simulated within a simplified OSSE framework and presented here. Ensemble simulations are produced from a cycling system that utilizes the Weather Research and Forecasting (WRF) model v3.8.1 within the Data Assimilation Research Testbed (DART). A "truth" (nature) simulation is produced by supplying a 3-km WRF run with GFS analyses and integrating the model forward 90 hours, from the beginning of ensemble initialization through the end of the forecast. Target locations for surface and radiosonde observations are computed 6, 12, and

  11. ANALYSIS OF FACTORS OF POSITIVE EMPLOYER BRAND FORMATION AMONG THE INTERNAL TARGET AUDIENCE

    OpenAIRE

    S. Tsymbalyuk

    2017-01-01

    Conceptual provisions that reveal the essence of the "employer brand" notion have been formulated. The connectivity between employer brand and the level of employees satisfaction of remuneration and work environment, availability of conditions for professional and career development, attitude of company management to employees has been established. Based on the research findings regression model of dependency of employer brand on factor characteristics has been developed.

  12. ANALYSIS OF FACTORS OF POSITIVE EMPLOYER BRAND FORMATION AMONG THE INTERNAL TARGET AUDIENCE

    Directory of Open Access Journals (Sweden)

    S. Tsymbalyuk

    2017-01-01

    Full Text Available Conceptual provisions that reveal the essence of the "employer brand" notion have been formulated. The connectivity between employer brand and the level of employees satisfaction of remuneration and work environment, availability of conditions for professional and career development, attitude of company management to employees has been established. Based on the research findings regression model of dependency of employer brand on factor characteristics has been developed.

  13. Knowledge construction on target costing: an analysis of surveys on factors that enhance its adoption and use

    Directory of Open Access Journals (Sweden)

    Kelly Cristina Mucio Marques

    2017-08-01

    Full Text Available The aim of this research was to analyze the findings and the comparability of surveys published between 2001 and 2011 about situational factors related to organizations’ adoption and use of Target Costing (TC, as a way to identify their contributions. The method used was a critical-interpretative literature analysis, highlighting the discussion of the research findings. The results found were: (1 the relation between the intensity of the competition and the adoption and use of TC was confirmed in the three studies on this theme, a sign that intense competition can enhance the adoption of TC; (2 the relation between the adoption and use of TC and environmental uncertainty was confirmed in one study; (3 with regard to the investigated strategies, no conclusions could be reached as, when adopting Porter’s typology, findings were contradictory and, in the typology by Miles and Snow, the two studies could not be compared, although one of them identified a relation between the usage rate of “costing” practices and the defenders strategy;(4 there are signs that large companies are more prone to the adoption and use of TC. This research revealed gaps in the understanding of factors that further the adoption and use of TC, which can be completed through future studies, and verified the difficulty to compare results among the surveys analyzed. Despite the importance of the theme for research and to help managers with possible decisions on the adoption of TC, this kind of study was not found in Brazilian journals, indicating the need to undertake such research in companies active in Brazil.

  14. Proteomics analysis of human obesity reveals the epigenetic factor HDAC4 as a potential target for obesity.

    Directory of Open Access Journals (Sweden)

    Mohamed Abu-Farha

    Full Text Available Sedentary lifestyle and excessive energy intake are prominent contributors to obesity; a major risk factors for the development of insulin resistance, type 2 diabetes and cardiovascular diseases. Elucidating the molecular mechanisms underlying these chronic conditions is of relevant importance as it might lead to the identification of novel anti-obesity targets. The purpose of the current study is to investigate differentially expressed proteins between lean and obese subjects through a shot-gun quantitative proteomics approach using peripheral blood mononuclear cells (PBMCs extracts as well as potential modulation of those proteins by physical exercise. Using this approach, a total of 47 proteins showed at least 1.5 fold change between lean and obese subjects. In obese, the proteomic profiling before and after 3 months of physical exercise showed differential expression of 38 proteins. Thrombospondin 1 (TSP1 was among the proteins that were upregulated in obese subjects and then decreased by physical exercise. Conversely, the histone deacetylase 4 (HDAC4 was downregulated in obese subjects and then induced by physical exercise. The proteomic data was further validated by qRT-PCR, Western blot and immunohistochemistry in both PBMCs and adipose tissue. We also showed that HDAC4 levels correlated positively with maximum oxygen consumption (VO2 Max but negatively with body mass index, percent body fat, and the inflammatory chemokine RANTES. In functional assays, our data indicated that ectopic expression of HDAC4 significantly impaired TNF-α-dependent activation of NF-κB, establishing thus a link between HDAC4 and regulation of the immune system. Together, the expression pattern of HDAC4 in obese subjects before and after physical exercise, its correlation with various physical, clinical and metabolic parameters along with its inhibitory effect on NF-κB are suggestive of a protective role of HDAC4 against obesity. HDAC4 could therefore represent

  15. HDG1 transcription factor targets

    NARCIS (Netherlands)

    Horstman, A.; Boutilier, K.A.; Sanchez Perez, Gabino

    2015-01-01

    The AIL transcription factor BABY BOOM (BBM) is required together with the related PLETHORA proteins for embryo and root meristem development and its expression is sufficient to confer pluripotency and totipotency to somatic tissues. We show that BBM and other AIL proteins interact with multiple

  16. Targeting the Epidermal Growth Factor Receptor in Addition to Chemotherapy in Patients with Advanced Pancreatic Cancer: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Jaseela Chiramel

    2017-04-01

    Full Text Available Overexpression of epidermal growth factor receptors (EGFR occurs in >90% of pancreatic ductal adenocarcinomas (PDACs and is associated with a poorer prognosis. A systematic review of electronic databases identified studies exploring the addition of EGFR-targeted treatment to chemotherapy in patients with locally advanced (LA/metastatic PDAC. Efficacy, safety and tolerability of EGFR-targeted therapy were explored using meta-analysis of randomised controlled trials (RCTs. Meta-regression was utilised to explore factors associated with improved prognosis (all studies and benefit from EGFR-targeted therapy (RCTs. Twenty-eight studies (7 RCTs and 21 cohort studies comprising 3718 patients were included. The addition of EGFR-targeted treatment to chemotherapy did not improve progression-free (pooled hazard ratio (HR: 0.90, p = 0.15 or overall survival (HR: 0.94, p = 0.18. EGFR-targeted therapy was associated with increased treatment-related deaths (pooled odds ratio (OR: 5.18, p = 0.007, and grade (G3/4 rash (OR: 4.82, p = 0.03. There was a borderline significant increase in G3/4 diarrhoea (OR: 1.75, p = 0.06, but no effect on treatment discontinuation without progression (OR: 0.87, p = 0.25. Neither G3/4 rash nor diarrhoea were associated with increased survival benefit from EGFR-targeted therapy. The effect of EGFR-targeted therapy on overall survival (OS appeared greater in studies with a greater proportion of LA rather than metastatic patients (R = −0.69, p < 0.001. Further studies in unselected patients with advanced PDAC are not warranted. The benefit from EGFR inhibitors may be limited to patient subgroups not yet clearly defined.

  17. Analysis of Lung Tumor Motion in a Large Sample: Patterns and Factors Influencing Precise Delineation of Internal Target Volume

    Energy Technology Data Exchange (ETDEWEB)

    Knybel, Lukas [Department of Oncology, University Hospital Ostrava, Ostrava (Czech Republic); VŠB-Technical University of Ostrava, Ostrava (Czech Republic); Cvek, Jakub, E-mail: Jakub.cvek@fno.cz [Department of Oncology, University Hospital Ostrava, Ostrava (Czech Republic); Molenda, Lukas; Stieberova, Natalie; Feltl, David [Department of Oncology, University Hospital Ostrava, Ostrava (Czech Republic)

    2016-11-15

    Purpose/Objective: To evaluate lung tumor motion during respiration and to describe factors affecting the range and variability of motion in patients treated with stereotactic ablative radiation therapy. Methods and Materials: Log file analysis from online respiratory tumor tracking was performed in 145 patients. Geometric tumor location in the lungs, tumor volume and origin (primary or metastatic), sex, and tumor motion amplitudes in the superior-inferior (SI), latero-lateral (LL), and anterior-posterior (AP) directions were recorded. Tumor motion variability during treatment was described using intrafraction/interfraction amplitude variability and tumor motion baseline changes. Tumor movement dependent on the tumor volume, position and origin, and sex were evaluated using statistical regression and correlation analysis. Results: After analysis of >500 hours of data, the highest rates of motion amplitudes, intrafraction/interfraction variation, and tumor baseline changes were in the SI direction (6.0 ± 2.2 mm, 2.2 ± 1.8 mm, 1.1 ± 0.9 mm, and −0.1 ± 2.6 mm). The mean motion amplitudes in the lower/upper geometric halves of the lungs were significantly different (P<.001). Motion amplitudes >15 mm were observed only in the lower geometric quarter of the lungs. Higher tumor motion amplitudes generated higher intrafraction variations (R=.86, P<.001). Interfraction variations and baseline changes >3 mm indicated tumors contacting mediastinal structures or parietal pleura. On univariate analysis, neither sex nor tumor origin (primary vs metastatic) was an independent predictive factor of different movement patterns. Metastatic lesions in women, but not men, showed significantly higher mean amplitudes (P=.03) and variability (primary, 2.7 mm; metastatic, 4.9 mm; P=.002) than primary tumors. Conclusion: Online tracking showed significant irregularities in lung tumor movement during respiration. Motion amplitude was significantly lower in upper lobe

  18. Analysis of Lung Tumor Motion in a Large Sample: Patterns and Factors Influencing Precise Delineation of Internal Target Volume

    International Nuclear Information System (INIS)

    Knybel, Lukas; Cvek, Jakub; Molenda, Lukas; Stieberova, Natalie; Feltl, David

    2016-01-01

    Purpose/Objective: To evaluate lung tumor motion during respiration and to describe factors affecting the range and variability of motion in patients treated with stereotactic ablative radiation therapy. Methods and Materials: Log file analysis from online respiratory tumor tracking was performed in 145 patients. Geometric tumor location in the lungs, tumor volume and origin (primary or metastatic), sex, and tumor motion amplitudes in the superior-inferior (SI), latero-lateral (LL), and anterior-posterior (AP) directions were recorded. Tumor motion variability during treatment was described using intrafraction/interfraction amplitude variability and tumor motion baseline changes. Tumor movement dependent on the tumor volume, position and origin, and sex were evaluated using statistical regression and correlation analysis. Results: After analysis of >500 hours of data, the highest rates of motion amplitudes, intrafraction/interfraction variation, and tumor baseline changes were in the SI direction (6.0 ± 2.2 mm, 2.2 ± 1.8 mm, 1.1 ± 0.9 mm, and −0.1 ± 2.6 mm). The mean motion amplitudes in the lower/upper geometric halves of the lungs were significantly different (P<.001). Motion amplitudes >15 mm were observed only in the lower geometric quarter of the lungs. Higher tumor motion amplitudes generated higher intrafraction variations (R=.86, P<.001). Interfraction variations and baseline changes >3 mm indicated tumors contacting mediastinal structures or parietal pleura. On univariate analysis, neither sex nor tumor origin (primary vs metastatic) was an independent predictive factor of different movement patterns. Metastatic lesions in women, but not men, showed significantly higher mean amplitudes (P=.03) and variability (primary, 2.7 mm; metastatic, 4.9 mm; P=.002) than primary tumors. Conclusion: Online tracking showed significant irregularities in lung tumor movement during respiration. Motion amplitude was significantly lower in upper lobe

  19. Critical analysis of the potential for the therapeutic targeting of the Sp1 transcription factor in pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Jutooru I

    2014-06-01

    Full Text Available Indira Jutooru,1 Gayathri Chadalapaka,1 Stephen Safe1,21Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX, USA; 2Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX, USAAbstract: Pancreatic ductal adenocarcinoma (PDAC is a major cause of cancer-related deaths in developed countries and, in 2013, it is estimated that in excess of 45,220 new cases were diagnosed in the United States. PDAC is a highly aggressive disease that invariably evades early diagnosis. The mean survival time for patients with metastatic disease is only 3–6 months, and only 20%–30% of pancreatic cancer patients are alive after 12 months. Because pancreatic cancers are frequently detected at an advanced stage, treatments have provided very limited improvements in tumor regression and overall survival times after diagnosis. 5-Fluorouracil alone or in combination with other drugs has been extensively used for treatment of advanced pancreatic cancer, and gemcitabine has partially replaced 5-fluorouracil as a treatment for pancreatic cancer. Gemcitabine provides increased clinical benefits in terms of response rate; however, future studies need to focus on developing treatment modalities that will improve the survival rate for pancreatic cancer patients. Specificity protein 1 (Sp1 is overexpressed in PDAC patients, and high expression is associated with poor prognosis, lymph node metastasis, and low survival. Knockdown studies have shown that Sp1 plays an important role in cell growth, angiogenesis, inflammation, survival, and metastasis. Sp1 expression is low in normal tissue when compared to tumor tissue, which makes Sp1 a potential target for development of new mechanism-based drugs for treatment of pancreatic cancer. Several drugs such as tolfenamic acid, betulinic acid, and methyl-2-cyano3,12-dioxooleana-1,9(11-dien-28-oate are shown to downregulate Sp1 expression through various pathways

  20. ChIP-on-chip analysis identifies IL-22 as direct target gene of ectopically expressed FOXP3 transcription factor in human T cells

    Directory of Open Access Journals (Sweden)

    Jeron Andreas

    2012-12-01

    Full Text Available Abstract Background The transcription factor (TF forkhead box P3 (FOXP3 is constitutively expressed at high levels in naturally occurring CD4+CD25+ regulatory T cells (nTregs. It is not only the most accepted marker for that cell population but is also considered lineage determinative. Chromatin immunoprecipitation (ChIP of TFs in combination with genomic tiling microarray analysis (ChIP-on-chip has been shown to be an appropriate tool for identifying FOXP3 transcription factor binding sites (TFBSs on a genome-wide scale. In combination with microarray expression analysis, the ChIP-on-chip technique allows identification of direct FOXP3 target genes. Results ChIP-on-chip analysis of the human FOXP3 expressed in resting and PMA/ionomycin–stimulated Jurkat T cells revealed several thousand putative FOXP3 binding sites and demonstrated the importance of intronic regions for FOXP3 binding. The analysis of expression data showed that the stimulation-dependent down-regulation of IL-22 was correlated with direct FOXP3 binding in the IL-22 promoter region. This association was confirmed by real-time PCR analysis of ChIP-DNA. The corresponding ChIP-region also contained a matching FOXP3 consensus sequence. Conclusions Knowledge of the general distribution patterns of FOXP3 TFBSs in the human genome under resting and activated conditions will contribute to a better understanding of this TF and its influence on direct target genes, as well as its importance for the phenotype and function of Tregs. Moreover, FOXP3-dependent repression of Th17-related IL-22 may be relevant to an understanding of the phenomenon of Treg/Th17 cell plasticity.

  1. Analysis Of Performance Factors Of Construction Management Consultant Affecting The Failure In Achieving Time And Quality Targets On Construction Project Of Samarinda Baru Airport

    Directory of Open Access Journals (Sweden)

    Maryudi Utomo

    2017-11-01

    Full Text Available This research aims to determine the performance factors of construction management consultants affecting the failure in achieving time and quality targets on construction project of Samarinda Baru Airport. This research uses survey method by collecting respondents opinion experience and attitude by taking primary data from questionnaires and secondary data from related institutions. The results of the research are 1 Factors directly affecting the Time Target Y1 are the Understanding of Contract Document X1 Material Requirements X3 Worker Requirements X4 and Equipment Completeness X5 while factors indirectly affecting the Time Target Y1 are the Understanding of Technical Specifications X2 and Local Government Regulations X7 2 Factors directly affecting the Quality Target Y2 are the Understanding of Contract Document X1 the Understanding of Technical Specifications X2 Material Requirements X3 Worker Requirements X4 Equipment Completeness X5 and Time Target Y1 while factor indirectly affecting the Quality Target Y1 is Local Government Regulations X7 3 The most dominant factor affecting the unsuccessful Time Target Y1 is the Worker Requirements X4 with the path coefficient value of 0.431. While the most dominant factor affecting the unsuccessful Quality Target Y2 is Worker Requirements X4 with path coefficient value of 0.579 4.

  2. Analysis Of Performance Factors Of Construction Management Consultant Affecting The Failure In Achieving Time And Quality Targets On Construction Project Of Samarinda Baru Airport

    OpenAIRE

    Maryudi Utomo; Kustamar; Bambang Wedyantadji

    2017-01-01

    This research aims to determine the performance factors of construction management consultants affecting the failure in achieving time and quality targets on construction project of Samarinda Baru Airport. This research uses survey method by collecting respondents opinion experience and attitude by taking primary data from questionnaires and secondary data from related institutions. The results of the research are 1 Factors directly affecting the Time Target Y1 are the Understanding of Contra...

  3. Non-Targeted Analysis Challenge (Non-targeted screening workshop)

    Science.gov (United States)

    This brief presentation is intended to motivate discussion of the "Non-Targeted Analysis Challenge" at the Advancing Non-Targeted Analyses of Xenobiotics in Environmental and Biological Media workshop held at the EPA RTP campus.

  4. TF Target Mapper: A BLAST search tool for the identification of Transcription Factor target genes

    Directory of Open Access Journals (Sweden)

    van der Spek Peter

    2006-03-01

    Full Text Available Abstract Background In the current era of high throughput genomics a major challenge is the genome-wide identification of target genes for specific transcription factors. Chromatin immunoprecipitation (ChIP allows the isolation of in vivo binding sites of transcription factors and provides a powerful tool for examining gene regulation. Crosslinked chromatin is immunoprecipitated with antibodies against specific transcription factors, thus enriching for sequences bound in vivo by these factors in the immunoprecipitated DNA. Cloning and sequencing the immunoprecipitated sequences allows identification of transcription factor target genes. Routinely, thousands of such sequenced clones are used in BLAST searches to map their exact location in the genome and the genes located in the vicinity. These genes represent potential targets of the transcription factor of interest. Such bioinformatics analysis is very laborious if performed manually and for this reason there is a need for developing bioinformatic tools to automate and facilitate it. Results In order to facilitate this analysis we generated TF Target Mapper (Transcription Factor Target Mapper. TF Target Mapper is a BLAST search tool allowing rapid extraction of annotated information on genes around each hit. It combines sequence cleaning/filtering, pattern searching and BLAST searches with extraction of information on genes located around each BLAST hit and comparisons of the output list of genes or gene ontology IDs with user-implemented lists. We successfully applied and tested TF Target Mapper to analyse sequences bound in vivo by the transcription factor GATA-1. We show that TF Target Mapper efficiently extracted information on genes around ChIPed sequences, thus identifying known (e.g. α-globin and ζ-globin and potentially novel GATA-1 gene targets. Conclusion TF Target Mapper is a very efficient BLAST search tool that allows the rapid extraction of annotated information on the genes

  5. Factor Analysis via Components Analysis

    Science.gov (United States)

    Bentler, Peter M.; de Leeuw, Jan

    2011-01-01

    When the factor analysis model holds, component loadings are linear combinations of factor loadings, and vice versa. This interrelation permits us to define new optimization criteria and estimation methods for exploratory factor analysis. Although this article is primarily conceptual in nature, an illustrative example and a small simulation show…

  6. Sparse Exploratory Factor Analysis.

    Science.gov (United States)

    Trendafilov, Nickolay T; Fontanella, Sara; Adachi, Kohei

    2017-07-13

    Sparse principal component analysis is a very active research area in the last decade. It produces component loadings with many zero entries which facilitates their interpretation and helps avoid redundant variables. The classic factor analysis is another popular dimension reduction technique which shares similar interpretation problems and could greatly benefit from sparse solutions. Unfortunately, there are very few works considering sparse versions of the classic factor analysis. Our goal is to contribute further in this direction. We revisit the most popular procedures for exploratory factor analysis, maximum likelihood and least squares. Sparse factor loadings are obtained for them by, first, adopting a special reparameterization and, second, by introducing additional [Formula: see text]-norm penalties into the standard factor analysis problems. As a result, we propose sparse versions of the major factor analysis procedures. We illustrate the developed algorithms on well-known psychometric problems. Our sparse solutions are critically compared to ones obtained by other existing methods.

  7. Bayesian Exploratory Factor Analysis

    DEFF Research Database (Denmark)

    Conti, Gabriella; Frühwirth-Schnatter, Sylvia; Heckman, James J.

    2014-01-01

    This paper develops and applies a Bayesian approach to Exploratory Factor Analysis that improves on ad hoc classical approaches. Our framework relies on dedicated factor models and simultaneously determines the number of factors, the allocation of each measurement to a unique factor, and the corr......This paper develops and applies a Bayesian approach to Exploratory Factor Analysis that improves on ad hoc classical approaches. Our framework relies on dedicated factor models and simultaneously determines the number of factors, the allocation of each measurement to a unique factor......, and the corresponding factor loadings. Classical identification criteria are applied and integrated into our Bayesian procedure to generate models that are stable and clearly interpretable. A Monte Carlo study confirms the validity of the approach. The method is used to produce interpretable low dimensional aggregates...

  8. A Computational Drug Repositioning Approach for Targeting Oncogenic Transcription Factors

    Directory of Open Access Journals (Sweden)

    Kaitlyn M. Gayvert

    2016-06-01

    Full Text Available Mutations in transcription factor (TF genes are frequently observed in tumors, often leading to aberrant transcriptional activity. Unfortunately, TFs are often considered undruggable due to the absence of targetable enzymatic activity. To address this problem, we developed CRAFTT, a computational drug-repositioning approach for targeting TF activity. CRAFTT combines ChIP-seq with drug-induced expression profiling to identify small molecules that can specifically perturb TF activity. Application to ENCODE ChIP-seq datasets revealed known drug-TF interactions, and a global drug-protein network analysis supported these predictions. Application of CRAFTT to ERG, a pro-invasive, frequently overexpressed oncogenic TF, predicted that dexamethasone would inhibit ERG activity. Dexamethasone significantly decreased cell invasion and migration in an ERG-dependent manner. Furthermore, analysis of electronic medical record data indicates a protective role for dexamethasone against prostate cancer. Altogether, our method provides a broadly applicable strategy for identifying drugs that specifically modulate TF activity.

  9. Bayesian Exploratory Factor Analysis

    Science.gov (United States)

    Conti, Gabriella; Frühwirth-Schnatter, Sylvia; Heckman, James J.; Piatek, Rémi

    2014-01-01

    This paper develops and applies a Bayesian approach to Exploratory Factor Analysis that improves on ad hoc classical approaches. Our framework relies on dedicated factor models and simultaneously determines the number of factors, the allocation of each measurement to a unique factor, and the corresponding factor loadings. Classical identification criteria are applied and integrated into our Bayesian procedure to generate models that are stable and clearly interpretable. A Monte Carlo study confirms the validity of the approach. The method is used to produce interpretable low dimensional aggregates from a high dimensional set of psychological measurements. PMID:25431517

  10. Older type 2 diabetic patients are more likely to achieve glycaemic and cardiovascular risk factors targets than younger patients: analysis of a primary care database.

    Science.gov (United States)

    Barrot-de la Puente, J; Mata-Cases, M; Franch-Nadal, J; Mundet-Tudurí, X; Casellas, A; Fernandez-Real, J M; Mauricio, D

    2015-12-01

    Older subjects with type 2 diabetes mellitus (T2DM) have differential characteristics compared with middle-aged or younger populations, and require tailored management of the disease. To evaluate how clinical characteristics, degree of control of glycaemia and cardiovascular risk factors, presence of chronic complications and treatments differ between older T2DM patients and younger adults. Cross-sectional study using data from a population-based electronic database. We retrieved data from 318,020 patients ≥ 30 years diagnosed with T2DM, attended during 2011 in primary care centres in Catalonia, Spain. We performed descriptive and comparative analyses stratified by gender and age subgroups: ≤ 65, 66-75, 76-85 and >85 years. Both men and women across older age subgroups (> 65 years) had longer diabetes duration than younger adults (8.0 vs. 5.6 in men and 8.4 vs. 6.9 years in women; p cardiovascular risk factors (p patients were more likely to achieve glycaemic targets irrespective of having cardiovascular disease. The use of oral antidiabetics decreased with increasing age, and insulin in monotherapy was more frequently prescribed among patients in the older age subgroups. Diabetes-related complications were more frequent in men of all group ages. In the older age subgroups, patients of both sexes had a longer duration of T2DM but better glycaemic control. In this context, the prevalence of diabetic retinopathy decreased unexpectedly with increasing age. Control of glycaemia and cardiovascular risk factors was better among older T2DM patients. There is a need for prospective studies to quantify the weight of risk factors in each complication to adapt the therapeutic and care approaches in elderly people. © 2015 The Authors. International Journal of Clinical Practice Published by John Wiley & Sons Ltd.

  11. Classifying transcription factor targets and discovering relevant biological features

    Directory of Open Access Journals (Sweden)

    DeLisi Charles

    2008-05-01

    Full Text Available Abstract Background An important goal in post-genomic research is discovering the network of interactions between transcription factors (TFs and the genes they regulate. We have previously reported the development of a supervised-learning approach to TF target identification, and used it to predict targets of 104 transcription factors in yeast. We now include a new sequence conservation measure, expand our predictions to include 59 new TFs, introduce a web-server, and implement an improved ranking method to reveal the biological features contributing to regulation. The classifiers combine 8 genomic datasets covering a broad range of measurements including sequence conservation, sequence overrepresentation, gene expression, and DNA structural properties. Principal Findings (1 Application of the method yields an amplification of information about yeast regulators. The ratio of total targets to previously known targets is greater than 2 for 11 TFs, with several having larger gains: Ash1(4, Ino2(2.6, Yaf1(2.4, and Yap6(2.4. (2 Many predicted targets for TFs match well with the known biology of their regulators. As a case study we discuss the regulator Swi6, presenting evidence that it may be important in the DNA damage response, and that the previously uncharacterized gene YMR279C plays a role in DNA damage response and perhaps in cell-cycle progression. (3 A procedure based on recursive-feature-elimination is able to uncover from the large initial data sets those features that best distinguish targets for any TF, providing clues relevant to its biology. An analysis of Swi6 suggests a possible role in lipid metabolism, and more specifically in metabolism of ceramide, a bioactive lipid currently being investigated for anti-cancer properties. (4 An analysis of global network properties highlights the transcriptional network hubs; the factors which control the most genes and the genes which are bound by the largest set of regulators. Cell-cycle and

  12. Exploratory Bi-Factor Analysis

    Science.gov (United States)

    Jennrich, Robert I.; Bentler, Peter M.

    2011-01-01

    Bi-factor analysis is a form of confirmatory factor analysis originally introduced by Holzinger. The bi-factor model has a general factor and a number of group factors. The purpose of this article is to introduce an exploratory form of bi-factor analysis. An advantage of using exploratory bi-factor analysis is that one need not provide a specific…

  13. Factor analysis and scintigraphy

    International Nuclear Information System (INIS)

    Di Paola, R.; Penel, C.; Bazin, J.P.; Berche, C.

    1976-01-01

    The goal of factor analysis is usually to achieve reduction of a large set of data, extracting essential features without previous hypothesis. Due to the development of computerized systems, the use of largest sampling, the possibility of sequential data acquisition and the increase of dynamic studies, the problem of data compression can be encountered now in routine. Thus, results obtained for compression of scintigraphic images were first presented. Then possibilities given by factor analysis for scan processing were discussed. At last, use of this analysis for multidimensional studies and specially dynamic studies were considered for compression and processing [fr

  14. Epidermal growth factor receptor: Target for delivery and silencing

    NARCIS (Netherlands)

    Santos Oliveira, S.|info:eu-repo/dai/nl/304841455

    2008-01-01

    Epidermal growth factor receptor in cancer therapy Recently, cancer research has been able to identify molecular targets that are specific for (or highly expressed by) cancer cells. These molecular targets serve as models for the development of rationally designed anticancer drugs that target

  15. Target Tracking Based Scene Analysis

    Science.gov (United States)

    1984-08-01

    NATO Advanced Study PG Institute, Braunlage/ Harz , FRG, June 21 July 2, 1I82 Springer, Berlin, 1983, pp. 493-501. 141 B. Bhanu."Recognition of...Braunlage/ Harz . FRG, June 21 - July 2, 1082 Springer, Berlin, 1083. pp 10.1-124. [81 R.B. Cate, T.*1B. Dennis, J.T. Mallin, K.S. Nedelman, NEIL Trenchard, and...34Image, Sequence Processing and Dynamic Scene Analysis", Proceedings of NATO,. Advanced Study Institute, Braunlage/ Harz , FRG, June 21 - July 2, 1982

  16. Identification of novel target genes of nerve growth factor (NGF) in human mastocytoma cell line (HMC-1 (V560G c-Kit)) by transcriptome analysis.

    Science.gov (United States)

    Dutta, Priyanka; Koch, Alexandra; Breyer, Bjoern; Schneider, Heike; Dittrich-Breiholz, Oliver; Kracht, Michael; Tamura, Teruko

    2011-04-18

    Nerve growth factor (NGF) is a potent growth factor that plays a key role in neuronal cell differentiation and may also play a role in hematopoietic differentiation. It has been shown that NGF induced synergistic action for the colony formation of CD34 positive hematopoietic progenitor cells treated with macrophage-colony stimulating factor (M-CSF or CSF-1), or stem cell factor (SCF). However, the exact role of NGF in hematopoietic system is unclear. It is also not clear whether NGF mediated signals in hematopoietic cells are identical to those in neuronal cells. To study the signal transduction pathways induced by NGF treatment in hematopoietic cells, we utilized the mastocytoma cell line HMC-1(V560G c-Kit) which expresses the NGF receptor, tropomyosin-receptor-kinase (Trk)A, as well as the constitutively activated SCF receptor, V560G c-Kit, which can be inhibited completely by treatment with the potent tyrosine kinase inhibitor imatinib mesylate (imatinib). NGF rescues HMC-1(V560G c-Kit) cells from imatinib mediated cell death and promotes proliferation. To examine the NGF mediated proliferation and survival in these cells, we compared the NGF mediated upregulated genes (30 and 120 min after stimulation) to the downregulated genes by imatinib treatment (downregulation of c-Kit activity for 4 h) by transcriptome analysis. The following conclusions can be drawn from the microarray data: Firstly, gene expression profiling reveals 50% overlap of genes induced by NGF-TrkA with genes expressed downstream of V560G c-Kit. Secondly, NGF treatment does not enhance expression of genes involved in immune related functions that were down regulated by imatinib treatment. Thirdly, more than 55% of common upregulated genes are involved in cell proliferation and survival. Fourthly, we found Kruppel-like factor (KLF) 2 and Smad family member 7 (SMAD7) as the NGF mediated novel downstream genes in hematopoietic cells. Finally, the downregulation of KLF2 gene enhanced imatinib

  17. RNA microarray analysis in prenatal mouse cochlea reveals novel IGF-I target genes: implication of MEF2 and FOXM1 transcription factors.

    Directory of Open Access Journals (Sweden)

    Hortensia Sanchez-Calderon

    2010-01-01

    Full Text Available Insulin-like growth factor-I (IGF-I provides pivotal cell survival and differentiation signals during inner ear development throughout evolution. Homozygous mutations of human IGF1 cause syndromic sensorineural deafness, decreased intrauterine and postnatal growth rates, and mental retardation. In the mouse, deficits in IGF-I result in profound hearing loss associated with reduced survival, differentiation and maturation of auditory neurons. Nevertheless, little is known about the molecular basis of IGF-I activity in hearing and deafness.A combination of quantitative RT-PCR, subcellular fractionation and Western blotting, along with in situ hybridization studies show IGF-I and its high affinity receptor to be strongly expressed in the embryonic and postnatal mouse cochlea. The expression of both proteins decreases after birth and in the cochlea of E18.5 embryonic Igf1(-/- null mice, the balance of the main IGF related signalling pathways is altered, with lower activation of Akt and ERK1/2 and stronger activation of p38 kinase. By comparing the Igf1(-/- and Igf1(+/+ transcriptomes in E18.5 mouse cochleae using RNA microchips and validating their results, we demonstrate the up-regulation of the FoxM1 transcription factor and the misexpression of the neural progenitor transcription factors Six6 and Mash1 associated with the loss of IGF-I. Parallel, in silico promoter analysis of the genes modulated in conjunction with the loss of IGF-I revealed the possible involvement of MEF2 in cochlear development. E18.5 Igf1(+/+ mouse auditory ganglion neurons showed intense MEF2A and MEF2D nuclear staining and MEF2A was also evident in the organ of Corti. At P15, MEF2A and MEF2D expression were shown in neurons and sensory cells. In the absence of IGF-I, nuclear levels of MEF2 were diminished, indicating less transcriptional MEF2 activity. By contrast, there was an increase in the nuclear accumulation of FoxM1 and a corresponding decrease in the nuclear cyclin

  18. Bayesian Factor Analysis.

    Science.gov (United States)

    1985-03-23

    Fundamantal Factors of Comprehension in...8217’"" . " *. . . . • * • "• "". . . . " . . . . • . . # • • • . .° - -.... . ... .. . . . . . . . . ................. 1 ,,.,..,*, University of Iowa/Novick 8 March 1985 Dr. James McBride Program Manager for Manpower, Psychological...Princeton, NJ 08541 Dr. Vern W. Urry Dr. Peter Stoloff Personnel R&D Center Center for Naval Analysis Office of Personnel Management 200 North

  19. psRNATarget: a plant small RNA target analysis server.

    Science.gov (United States)

    Dai, Xinbin; Zhao, Patrick Xuechun

    2011-07-01

    Plant endogenous non-coding short small RNAs (20-24 nt), including microRNAs (miRNAs) and a subset of small interfering RNAs (ta-siRNAs), play important role in gene expression regulatory networks (GRNs). For example, many transcription factors and development-related genes have been reported as targets of these regulatory small RNAs. Although a number of miRNA target prediction algorithms and programs have been developed, most of them were designed for animal miRNAs which are significantly different from plant miRNAs in the target recognition process. These differences demand the development of separate plant miRNA (and ta-siRNA) target analysis tool(s). We present psRNATarget, a plant small RNA target analysis server, which features two important analysis functions: (i) reverse complementary matching between small RNA and target transcript using a proven scoring schema, and (ii) target-site accessibility evaluation by calculating unpaired energy (UPE) required to 'open' secondary structure around small RNA's target site on mRNA. The psRNATarget incorporates recent discoveries in plant miRNA target recognition, e.g. it distinguishes translational and post-transcriptional inhibition, and it reports the number of small RNA/target site pairs that may affect small RNA binding activity to target transcript. The psRNATarget server is designed for high-throughput analysis of next-generation data with an efficient distributed computing back-end pipeline that runs on a Linux cluster. The server front-end integrates three simplified user-friendly interfaces to accept user-submitted or preloaded small RNAs and transcript sequences; and outputs a comprehensive list of small RNA/target pairs along with the online tools for batch downloading, key word searching and results sorting. The psRNATarget server is freely available at http://plantgrn.noble.org/psRNATarget/.

  20. Genome-Wide Chromosomal Targets of Oncogenic Transcription Factors

    National Research Council Canada - National Science Library

    Lyer, Vishwanath R

    2006-01-01

    .... Our work over the past year has successfully identified targets of c-Myc, E2F4 and Stat1, all factors important in breast cancer, and our data supports the idea that it is possible to comprehensively...

  1. A Computational Drug Repositioning Approach for Targeting Oncogenic Transcription Factors

    OpenAIRE

    Gayvert, Kaitlyn; Dardenne, Etienne; Cheung, Cynthia; Boland, Mary Regina; Lorberbaum, Tal; Wanjala, Jackline; Chen, Yu; Rubin, Mark; Tatonetti, Nicholas P.; Rickman, David; Elemento, Olivier

    2016-01-01

    Mutations in transcription factors (TFs) genes are frequently observed in tumors, often leading to aberrant transcriptional activity. Unfortunately, TFs are often considered undruggable due to the absence of targetable enzymatic activity. To address this problem, we developed CRAFTT, a Computational drug-Repositioning Approach For Targeting Transcription factor activity. CRAFTT combines ChIP-seq with drug-induced expression profiling to identify small molecules that can specifically perturb T...

  2. Optimisation of high-performance liquid chromatography with diode array detection using an automatic peak tracking procedure based on augmented iterative target transformation factor analysis

    NARCIS (Netherlands)

    van Zomeren, Paul; Hoogvorst, A.; Coenegracht, P.M J; de Jong, G.J.

    2004-01-01

    An automated method for the optimisation of high-performance liquid chromatography is developed. First of all, the sample of interest is analysed with various eluent compositions. All obtained data are combined into one augmented data matrix. Subsequently, augmented iterative target transformation

  3. TF Target Mapper: a BLAST search tool for the identification of Transcription Factor target genes.

    NARCIS (Netherlands)

    S. Horsman (Sebastiaan); M.J. Moorhouse (Michael); V. de Jager (Victor); P.J. van der Spek (Peter); F.G. Grosveld (Frank); J. Strouboulis (John); E. Katsantoni (Eleni)

    2006-01-01

    textabstractBACKGROUND: In the current era of high throughput genomics a major challenge is the genome-wide identification of target genes for specific transcription factors. Chromatin immunoprecipitation (ChIP) allows the isolation of in vivo binding sites of transcription factors and provides a

  4. CFD analysis of the HYPER spallation target

    International Nuclear Information System (INIS)

    Cho, Chungho; Tak, Nam-il; Choi, Jae-Hyuk; Lee, Yong-Bum

    2008-01-01

    KAERI (Korea Atomic Energy Research Institute) is developing an accelerator driven system (ADS) named HYPER (HYbrid Power Extraction Reactor) for a transmutation of long-lived nuclear wastes. One of the challenging tasks for the HYPER system is to design a large spallation target with a beam power of 15-25 MW. The paper focuses on a thermal-hydraulic analysis of the active part of the HYPER target. Computational fluid dynamics (CFD) analysis was performed by using a commercial code CFX 5.7.1. Several advanced turbulence models with different grid structures were applied. The CFX results reveal a significant impact of the turbulence model on the window temperature. Particularly, the k-ε model predicts the lowest window temperature among the five investigated turbulence models

  5. An evaluation of energy-environment-economic efficiency for EU, APEC and ASEAN countries: Design of a Target-Oriented DFM model with fixed factors in Data Envelopment Analysis

    International Nuclear Information System (INIS)

    Suzuki, Soushi; Nijkamp, Peter

    2016-01-01

    This paper aims to offer an advanced assessment methodology for sustainable national energy-environment-economic efficiency strategies, based on an extended Data Envelopment Analysis (DEA). The use of novel efficiency-improving approaches based on DEA originates from the so-called Distance Friction Minimisation (DFM) method. To design a feasible improvement strategy for low-efficiency DMUs, we develop here a Target-Oriented (TO) DFM model. However, in many real-world cases input factors may not be flexibly adjusted in the short run. In this study, we integrate the TO-DFM model with a fixed (inflexible) factor (FF) approach to cope with such more realistic circumstances. Super-efficiency DEA is next used in our comparative study on the efficiency assessment of energy-environment-economic targets for the EU, APEC and ASEAN (A&A) countries, employing appropriate data sets from the years 2003 to 2012. We consider two inputs (primary energy consumption and population) and two outputs (CO 2 and GDP), including a fixed input factor (viz. population). On the basis of our DEA analysis results, EU countries appear to exhibit generally a higher efficiency than A&A countries. The above-mentioned TO-DFM-FF projection model is able to address realistic circumstances and requirements in an operational sustainability strategy for efficiency improvement in inefficient countries in the A&A region. - Highlights: • We examine energy-environment-economic efficiency in European and A&A countries. • We present an operational efficiency improvement strategy using DEA. • European countries tend to have higher energy efficiency than A&A countries. • The study provides efficiency-enhancing strategic paths for inefficient countries.

  6. Factors affecting construction performance: exploratory factor analysis

    Science.gov (United States)

    Soewin, E.; Chinda, T.

    2018-04-01

    The present work attempts to develop a multidimensional performance evaluation framework for a construction company by considering all relevant measures of performance. Based on the previous studies, this study hypothesizes nine key factors, with a total of 57 associated items. The hypothesized factors, with their associated items, are then used to develop questionnaire survey to gather data. The exploratory factor analysis (EFA) was applied to the collected data which gave rise 10 factors with 57 items affecting construction performance. The findings further reveal that the items constituting ten key performance factors (KPIs) namely; 1) Time, 2) Cost, 3) Quality, 4) Safety & Health, 5) Internal Stakeholder, 6) External Stakeholder, 7) Client Satisfaction, 8) Financial Performance, 9) Environment, and 10) Information, Technology & Innovation. The analysis helps to develop multi-dimensional performance evaluation framework for an effective measurement of the construction performance. The 10 key performance factors can be broadly categorized into economic aspect, social aspect, environmental aspect, and technology aspects. It is important to understand a multi-dimension performance evaluation framework by including all key factors affecting the construction performance of a company, so that the management level can effectively plan to implement an effective performance development plan to match with the mission and vision of the company.

  7. Alzheimer’s disease: Risk factors and therapeutic targets

    Directory of Open Access Journals (Sweden)

    Laxman Pokhrel

    2015-09-01

    Full Text Available Alzheimer’s disease (AD, a neurodegenerative disorder, has been determined as an outcome of genetic as well as behavioral conditions. The complete understanding of its generation and progress is yet to be understood. However, there has been a significant progress in the diagnosis and identification of the associated risk factors of AD. Several of the risk factors were found connected with cholesterol. Scientists are mainly focusing on the reduction of amyloid β and stabilization of tau protein towards the development of its drugs. To modulate amyloid β, the key components of cholesterol metabolism have been attractive targets and the enzymes involved in the phosphorylation of tau have been tried to stabilize tau protein. This review article briefly highlights the symptoms, risk factors, and drug targets of AD.

  8. Drug-Target Interaction Prediction with Graph Regularized Matrix Factorization.

    Science.gov (United States)

    Ezzat, Ali; Zhao, Peilin; Wu, Min; Li, Xiao-Li; Kwoh, Chee-Keong

    2017-01-01

    Experimental determination of drug-target interactions is expensive and time-consuming. Therefore, there is a continuous demand for more accurate predictions of interactions using computational techniques. Algorithms have been devised to infer novel interactions on a global scale where the input to these algorithms is a drug-target network (i.e., a bipartite graph where edges connect pairs of drugs and targets that are known to interact). However, these algorithms had difficulty predicting interactions involving new drugs or targets for which there are no known interactions (i.e., "orphan" nodes in the network). Since data usually lie on or near to low-dimensional non-linear manifolds, we propose two matrix factorization methods that use graph regularization in order to learn such manifolds. In addition, considering that many of the non-occurring edges in the network are actually unknown or missing cases, we developed a preprocessing step to enhance predictions in the "new drug" and "new target" cases by adding edges with intermediate interaction likelihood scores. In our cross validation experiments, our methods achieved better results than three other state-of-the-art methods in most cases. Finally, we simulated some "new drug" and "new target" cases and found that GRMF predicted the left-out interactions reasonably well.

  9. Nuclear Security: Target Analysis-rev

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Surinder Paul [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Gibbs, Philip W. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Bultz, Garl A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2014-03-01

    The objectives of this presentation are to understand target identification, including roll-up and protracted theft; evaluate target identification in the SNRI; recognize the target characteristics and consequence levels; and understand graded safeguards.

  10. Factors leading to inflation targeting - the impact of adoption

    NARCIS (Netherlands)

    Samarina, Anna; Sturm, Jan-Egbert

    2013-01-01

    This paper examines how the analysis of inflation targeting (IT) adoption is affected by the choice of the analyzed period. We test whether country characteristics influence the decision to apply IT differently before and after its adoption, using panel probit models for 60 countries over the period

  11. Factors leading to inflation targeting : The impact of adoption

    NARCIS (Netherlands)

    Samarina, Anna; Sturm, Jan-Egbert

    2013-01-01

    This paper examines how the analysis of inflation targeting (IT) adoption is affected by allowing for a structural change after adoption, using panel probit models for 60 countries over the period 1985-2008. Our findings suggest that there is a structural change after IT adoption. Including the

  12. Error Analysis of Fast Moving Target Geo-location in Wide Area Surveillance Ground Moving Target Indication Mode

    Directory of Open Access Journals (Sweden)

    Zheng Shi-chao

    2013-12-01

    Full Text Available As an important mode in airborne radar systems, Wide Area Surveillance Ground Moving Target Indication (WAS-GMTI mode has the ability of monitoring a large area in a short time, and then the detected moving targets can be located quickly. However, in real environment, many factors introduce considerable errors into the location of moving targets. In this paper, a fast location method based on the characteristics of the moving targets in WAS-GMTI mode is utilized. And in order to improve the location performance, those factors that introduce location errors are analyzed and moving targets are relocated. Finally, the analysis of those factors is proved to be reasonable by simulation and real data experiments.

  13. Factor analysis of multivariate data

    Digital Repository Service at National Institute of Oceanography (India)

    Fernandes, A.A.; Mahadevan, R

    A brief introduction to factor analysis is presented. A FORTRAN program, which can perform the Q-mode and R-mode factor analysis and the singular value decomposition of a given data matrix is presented in Appendix B. This computer program, uses...

  14. Factor Analysis of Intern Effectiveness

    Science.gov (United States)

    Womack, Sid T.; Hannah, Shellie Louise; Bell, Columbus David

    2012-01-01

    Four factors in teaching intern effectiveness, as measured by a Praxis III-similar instrument, were found among observational data of teaching interns during the 2010 spring semester. Those factors were lesson planning, teacher/student reflection, fairness & safe environment, and professionalism/efficacy. This factor analysis was as much of a…

  15. Factor analysis and missing data

    NARCIS (Netherlands)

    Kamakura, WA; Wedel, M

    2000-01-01

    The authors study the estimation of factor models and the imputation of missing data and propose an approach that provides direct estimates of factor weights without the replacement of missing data with imputed values. First, the approach is useful in applications of factor analysis in the presence

  16. Targeted Cancer Therapy with Tumor Necrosis Factor-Alpha

    Directory of Open Access Journals (Sweden)

    Weibo Cai Ph.D.

    2008-01-01

    Full Text Available Tumor necrosis factor-alpha (TNF-α, a member of the TNF superfamily, was the first cytokine to be evaluated for cancer biotherapy. However, the clinical use of TNF-α is severely limited by its toxicity. Currently, TNF-α is administered only through locoregional drug delivery systems such as isolated limb perfusion and isolated hepatic perfusion. To reduce the systemic toxicity of TNF-α, various strategies have been explored over the last several decades. This review summarizes current state-of-the-art targeted cancer therapy using TNF-α. Passive targeting, cell-based therapy, gene therapy with inducible or tissue-specific promoters, targeted polymer-DNA complexes, tumor pre-targeting, antibody-TNF-α conjugate, scFv/TNF-α fusion proteins, and peptide/TNF-α fusion proteins have all been investigated to combat cancer. Many of these agents are already in advanced clinical trials. Molecular imaging, which can significantly speed up the drug development process, and nanomedicine, which can integrate both imaging and therapeutic components, has the potential to revolutionize future cancer patient management. Cooperative efforts from scientists within multiple disciplines, as well as close partnerships among many organizations/entities, are needed to quickly translate novel TNF-α-based therapeutics into clinical investigation.

  17. Targeting the epidermal growth factor receptor in solid tumor malignancies

    DEFF Research Database (Denmark)

    Nedergaard, Mette K; Hedegaard, Chris J; Poulsen, Hans S

    2012-01-01

    to the extracellular part of EGFR, blocking the binding sites for the EGFR ligands, and intracellular tyrosine kinase inhibitors (TKIs) that block the ATP binding site of the tyrosine kinase domain. Besides an EGFRvIII-targeted vaccine, conjugated anti-EGFR mAbs have been used in different settings to deliver lethal......The epidermal growth factor receptor (EGFR) is over-expressed, as well as mutated, in many types of cancers. In particular, the EGFR variant type III mutant (EGFRvIII) has attracted much attention as it is frequently and exclusively found on many tumor cells, and hence both EGFR and EGFRvIII have...... been proposed as valid targets in many cancer therapy settings. Different strategies have been developed in order to either inhibit EGFR/EGFRvIII activity or to ablate EGFR/EGFRvIII-positive tumor cells. Drugs that inhibit these receptors include monoclonal antibodies (mAbs) that bind...

  18. A computational network analysis based on targets of antipsychotic agents.

    Science.gov (United States)

    Gao, Lei; Feng, Shuo; Liu, Zhao-Yuan; Wang, Jiu-Qiang; Qi, Ke-Ke; Wang, Kai

    2018-03-01

    Currently, numerous antipsychotic agents have been developed in the area of pharmacological treatment of schizophrenia. However, the molecular mechanism underlying multi targets of antipsychotics were yet to be explored. In this study we performed a computational network analysis based on targets of antipsychotic agents. We retrieved a total of 96 targets from 56 antipsychotic agents. By expression enrichment analysis, we identified that the expressions of antipsychotic target genes were significantly enriched in liver, brain, blood and corpus striatum. By protein-protein interaction (PPI) network analysis, a PPI network with 77 significantly interconnected target genes was generated. By historeceptomics analysis, significant brain region specific target-drug interactions were identified in targets of dopamine receptors (DRD1-Olanzapine in caudate nucleus and pons (P-valueantipsychotic targets and insights for molecular mechanism of antipsychotic agents. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Neutron performance analysis for ESS target proposal

    International Nuclear Information System (INIS)

    Magán, M.; Terrón, S.; Thomsen, K.; Sordo, F.; Perlado, J.M.; Bermejo, F.J.

    2012-01-01

    In the course of discussing different target types for their suitability in the European Spallation Source (ESS) one main focus was on neutronics' performance. Diverse concepts have been assessed baselining some preliminary engineering and geometrical details and including some optimization. With the restrictions and resulting uncertainty imposed by the lack of detailed designs optimizations at the time of compiling this paper, the conclusion drawn is basically that there is a little difference in the neutronic yield of the investigated targets. Other criteria like safety, environmental compatibility, reliability and cost will thus dominate the choice of an ESS target.

  20. First course in factor analysis

    CERN Document Server

    Comrey, Andrew L

    2013-01-01

    The goal of this book is to foster a basic understanding of factor analytic techniques so that readers can use them in their own research and critically evaluate their use by other researchers. Both the underlying theory and correct application are emphasized. The theory is presented through the mathematical basis of the most common factor analytic models and several methods used in factor analysis. On the application side, considerable attention is given to the extraction problem, the rotation problem, and the interpretation of factor analytic results. Hence, readers are given a background of

  1. Molecular Composition Analysis of Distant Targets

    Data.gov (United States)

    National Aeronautics and Space Administration — We propose a system capable of probing the molecular composition of cold solar system targets such as asteroids, comets, planets and moons from a distant vantage....

  2. Lithuanian Population Aging Factors Analysis

    Directory of Open Access Journals (Sweden)

    Agnė Garlauskaitė

    2015-05-01

    Full Text Available The aim of this article is to identify the factors that determine aging of Lithuania’s population and to assess the influence of these factors. The article shows Lithuanian population aging factors analysis, which consists of two main parts: the first describes the aging of the population and its characteristics in theoretical terms. Second part is dedicated to the assessment of trends that influence the aging population and demographic factors and also to analyse the determinants of the aging of the population of Lithuania. After analysis it is concluded in the article that the decline in the birth rate and increase in the number of emigrants compared to immigrants have the greatest impact on aging of the population, so in order to show the aging of the population, a lot of attention should be paid to management of these demographic processes.

  3. Transforming Rubrics Using Factor Analysis

    Science.gov (United States)

    Baryla, Ed; Shelley, Gary; Trainor, William

    2012-01-01

    Student learning and program effectiveness is often assessed using rubrics. While much time and effort may go into their creation, it is equally important to assess how effective and efficient the rubrics actually are in terms of measuring competencies over a number of criteria. This study demonstrates the use of common factor analysis to identify…

  4. Hydrodynamic and symmetry safety factors of HiPER's targets

    Energy Technology Data Exchange (ETDEWEB)

    Hallo, L; Olazabal-Loume, M; Ribeyre, X; Drean, V; Schurtz, G; Feugeas, J-L; Breil, J; Nicolai, Ph; Maire, P-H [CELIA, Universite Bordeaux 1, 351 cours de La Liberation, 33405 Talence (France)], E-mail: hallo@celia.u-bordeaux1.fr

    2009-01-15

    Hydrodynamics and robustness of three high yield targets within the HiPER project are presented. Using realistic illumination nonuniformity configuration, hydrodynamic perturbations sensitivity analysis is carried out. A rather simple hydrodynamic perturbation modeling sequence is validated thanks to 2D simulations. 1D simulations post-processed with such a modeling sequence provide a good estimation of the thermonuclear burn. First estimates of hydrodynamic safety factor are given.

  5. Targeting TBP-associated factors in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Jennifer R Ribeiro

    2014-03-01

    Full Text Available As ovarian tumors progress, they undergo a process of dedifferentiation, allowing adaptive changes in growth and morphology that promote metastasis and chemoresistance. Herein, we outline a hypothesis that TATA-box binding protein (TBP associated factors (TAFs, which compose the RNA Polymerase II initiation factor, TFIID, contribute to regulation of dedifferentiation states in ovarian cancer. Numerous studies demonstrate that TAFs regulate differentiation and proliferation states; their expression is typically high in pluripotent cells and reduced upon differentiation. Strikingly, TAF2 exhibits copy number increases or mRNA overexpression in 73% of high grade serous ovarian cancers (HGSC. At the biochemical level, TAF2 directs TFIID to TATA-less promoters by contact with an Initiator element, which may lead to the deregulation of the transcriptional output of these tumor cells. TAF4, which is altered in 66% of HGSC, is crucial for the stability of the TFIID complex and helps drive dedifferentiation of mouse embryonic fibroblasts to induced pluripotent stem cells. Its ovary-enriched paralog, TAF4B, is altered in 26% of HGSC. Here, we show that Taf4b mRNA correlates with Cyclin D2 mRNA expression in human granulosa cell tumors. TAF4B may also contribute to regulation of tumor microenvironment due to its estrogen-responsiveness and ability to act as a cofactor for NFκB. Conversely, TAF9, a cofactor for p53 in regulating apoptosis, may act as a tumor suppressor in ovarian cancer, since it is downregulated or deleted in 98% of HGSC. We conclude that a greater understanding of mechanisms of transcriptional regulation that execute signals from oncogenic signaling cascades is needed in order to expand our understanding of the etiology and progression of ovarian cancer, and most importantly to identify novel targets for therapeutic intervention.

  6. Monetary targeting and financial system characteristics : An empirical analysis

    NARCIS (Netherlands)

    Samarina, A..

    2012-01-01

    This paper investigates how reforms and characteristics of the financial system affect the likelihood of countries to abandon their strategy of monetary targeting. Apart from financial system characteristics, we include macroeconomic, fiscal, and institutional factors potentially associated with

  7. Methodology of human factor analysis

    International Nuclear Information System (INIS)

    Griffon-Fouco, M.

    1988-01-01

    The paper describes the manner in which the Heat Production Department of Electricite de France analyses the human factors in nuclear power plants. After describing the teams and structures set up to deal with this subject, the paper emphasizes two types of methods which are used, most often in complementary fashion: (1) an a posteriori analysis, which consists in studying the events which have taken place at nuclear power plants and in seeking the deepseated causes so as to prevent their reoccurrence in future; (2) an a priori analysis, which consists in analysing a work situation and in detecting all its potential failure factors so as to prevent their resulting once again in dysfunctions of the facility. To illustrate these two types of analysis, two examples are given: first, a study of the telephonic communications between operators in one plant (in which the a posteriori and a priori analysis are developed) and, second, a study of stress in a plant (in which only the a priori analysis is used). (author). 1 tab

  8. Identification of target genes of transcription factor activator protein 2 gamma in breast cancer cells

    International Nuclear Information System (INIS)

    Ailan, He; Shuanglin, Xiang; Xiangwen, Xiao; Daolong, Ren; Lu, Gan; Xiaofeng, Ding; Xi, Qiao; Xingwang, Hu; Rushi, Liu; Jian, Zhang

    2009-01-01

    Activator protein 2 gamma (AP-2γ) is a member of the transcription factor activator protein-2 (AP-2) family, which is developmentally regulated and plays a role in human neoplasia. AP-2γ has been found to be overexpressed in most breast cancers, and have a dual role to inhibit tumor initiation and promote tumor progression afterwards during mammary tumorigensis. To identify the gene targets that mediate its effects, we performed chromatin immunoprecipitation (ChIP) to isolate AP-2γ binding sites on genomic DNA from human breast cancer cell line MDA-MB-453. 20 novel DNA fragments proximal to potential AP-2γ targets were obtained. They are categorized into functional groups of carcinogenesis, metabolism and others. A combination of sequence analysis, reporter gene assays, quantitative real-time PCR, electrophoretic gel mobility shift assays and immunoblot analysis further confirmed the four AP-2γ target genes in carcinogenesis group: ErbB2, CDH2, HPSE and IGSF11. Our results were consistent with the previous reports that ErbB2 was the target gene of AP-2γ. Decreased expression and overexpression of AP-2γ in human breast cancer cells significantly altered the expression of these four genes, indicating that AP-2γ directly regulates them. This suggested that AP-2γ can coordinate the expression of a network of genes, involving in carcinogenesis, especially in breast cancer. They could serve as therapeutic targets against breast cancers in the future

  9. Thermal Hydraulic and Structural Analysis of Liquid Metal Target System

    International Nuclear Information System (INIS)

    Lee, Yong Suk; Chung, Chang Hyun

    2002-01-01

    A subcritical transmutation reactor research is in progress for treatment of spent fuel. The subcritical transmutation reactor needs target system to produce high-energy neutrons. In target system, beam window is subject to high thermal field, because it interacts with high energy proton beam. In this study, target was designed based on thermal-hydraulic analysis, and thermal-structural analysis of window was performed. Preliminary design and mechanical analysis of liquid Pb-Bi target and 9Cr-2WVTa window were performed. Target was designed in a way to decrease window temperature. Installation of diffuse plate which has higher porosity in central zone was considered. Temperature and stress of window were analyzed varying minimum window thickness, beam power, and coolant flow rate. Thermal-bending stress was generated in window because of temperature gradient along the thickness of window. Coolant flow rate had insignificant effect on window stresses. It can be concluded that the target and window can be used in transmutation reactor operating condition (1 GeV, 6.78 mA). In this study, only static analysis has been made. But, accelerator beam trip can frequently occur in accelerator operation, so window and target container dynamic stress analysis will be needed. Furthermore, study about corrosion or irradiation characteristics of window will be needed in designing target and window. (authors)

  10. Integrative Analysis of CRISPR/Cas9 Target Sites in the Human HBB Gene

    Directory of Open Access Journals (Sweden)

    Yumei Luo

    2015-01-01

    Full Text Available Recently, the clustered regularly interspaced short palindromic repeats (CRISPR system has emerged as a powerful customizable artificial nuclease to facilitate precise genetic correction for tissue regeneration and isogenic disease modeling. However, previous studies reported substantial off-target activities of CRISPR system in human cells, and the enormous putative off-target sites are labor-intensive to be validated experimentally, thus motivating bioinformatics methods for rational design of CRISPR system and prediction of its potential off-target effects. Here, we describe an integrative analytical process to identify specific CRISPR target sites in the human β-globin gene (HBB and predict their off-target effects. Our method includes off-target analysis in both coding and noncoding regions, which was neglected by previous studies. It was found that the CRISPR target sites in the introns have fewer off-target sites in the coding regions than those in the exons. Remarkably, target sites containing certain transcriptional factor motif have enriched binding sites of relevant transcriptional factor in their off-target sets. We also found that the intron sites have fewer SNPs, which leads to less variation of CRISPR efficiency in different individuals during clinical applications. Our studies provide a standard analytical procedure to select specific CRISPR targets for genetic correction.

  11. Extension Procedures for Confirmatory Factor Analysis

    Science.gov (United States)

    Nagy, Gabriel; Brunner, Martin; Lüdtke, Oliver; Greiff, Samuel

    2017-01-01

    We present factor extension procedures for confirmatory factor analysis that provide estimates of the relations of common and unique factors with external variables that do not undergo factor analysis. We present identification strategies that build upon restrictions of the pattern of correlations between unique factors and external variables. The…

  12. Towards understanding the lifespan extension by reduced insulin signaling: bioinformatics analysis of DAF-16/FOXO direct targets in Caenorhabditis elegans.

    Science.gov (United States)

    Li, Yan-Hui; Zhang, Gai-Gai

    2016-04-12

    DAF-16, the C. elegans FOXO transcription factor, is an important determinant in aging and longevity. In this work, we manually curated FOXODB http://lyh.pkmu.cn/foxodb/, a database of FOXO direct targets. It now covers 208 genes. Bioinformatics analysis on 109 DAF-16 direct targets in C. elegans found interesting results. (i) DAF-16 and transcription factor PQM-1 co-regulate some targets. (ii) Seventeen targets directly regulate lifespan. (iii) Four targets are involved in lifespan extension induced by dietary restriction. And (iv) DAF-16 direct targets might play global roles in lifespan regulation.

  13. Kinetic analysis of the effects of target structure on siRNA efficiency

    Science.gov (United States)

    Chen, Jiawen; Zhang, Wenbing

    2012-12-01

    RNAi efficiency for target cleavage and protein expression is related to the target structure. Considering the RNA-induced silencing complex (RISC) as a multiple turnover enzyme, we investigated the effect of target mRNA structure on siRNA efficiency with kinetic analysis. The 4-step model was used to study the target cleavage kinetic process: hybridization nucleation at an accessible target site, RISC-mRNA hybrid elongation along with mRNA target structure melting, target cleavage, and enzyme reactivation. At this model, the terms accounting for the target accessibility, stability, and the seed and the nucleation site effects are all included. The results are in good agreement with that of experiments which show different arguments about the structure effects on siRNA efficiency. It shows that the siRNA efficiency is influenced by the integrated factors of target's accessibility, stability, and the seed effects. To study the off-target effects, a simple model of one siRNA binding to two mRNA targets was designed. By using this model, the possibility for diminishing the off-target effects by the concentration of siRNA was discussed.

  14. An easy guide to factor analysis

    CERN Document Server

    Kline, Paul

    2014-01-01

    Factor analysis is a statistical technique widely used in psychology and the social sciences. With the advent of powerful computers, factor analysis and other multivariate methods are now available to many more people. An Easy Guide to Factor Analysis presents and explains factor analysis as clearly and simply as possible. The author, Paul Kline, carefully defines all statistical terms and demonstrates step-by-step how to work out a simple example of principal components analysis and rotation. He further explains other methods of factor analysis, including confirmatory and path analysis, a

  15. Right on target: Exploring the factors leading to inflation targeting adoption

    NARCIS (Netherlands)

    Samarina, A..; de Haan, J.

    2014-01-01

    This paper examines which economic, fiscal, external, financial, and institutional characteristics of countries affect the likelihood that they adopt inflation targeting (IT) as their monetary policy strategy. We estimate a panel binary response model for 60 countries and two subsamples consisting

  16. Epidermal growth factor receptor is a preferred target for treating amyloid-β-induced memory loss.

    Science.gov (United States)

    Wang, Lei; Chiang, Hsueh-Cheng; Wu, Wenjuan; Liang, Bin; Xie, Zuolei; Yao, Xinsheng; Ma, Weiwei; Du, Shuwen; Zhong, Yi

    2012-10-09

    Current understanding of amyloid-β (Aβ) metabolism and toxicity provides an extensive list of potential targets for developing drugs for treating Alzheimer's disease. We took two independent approaches, including synaptic-plasticity-based analysis and behavioral screening of synthetic compounds, for identifying single compounds that are capable of rescuing the Aβ-induced memory loss in both transgenic fruit fly and transgenic mouse models. Two clinically available drugs and three synthetic compounds not only showed positive effects in behavioral tests but also antagonized the Aβ oligomers-induced activation of the epidermal growth factor receptor (EGFR). Such surprising converging outcomes from two parallel approaches lead us to conclude that EGFR is a preferred target for treating Aβ-induced memory loss.

  17. Vascular Risk Factors as Treatment Target to Prevent Cognitive Decline

    NARCIS (Netherlands)

    Richard, Edo; Moll van Charante, Eric P.; van Gool, Willem A.

    2012-01-01

    Epidemiological studies have consistently shown that vascular risk factors including hypertension, diabetes, obesity, hypercholesterolemia, smoking, and lack of physical exercise are associated with an increased risk of cognitive decline and dementia. Neuroradiological and neuropathological studies

  18. [Segment analysis of the target market of physiotherapeutic services].

    Science.gov (United States)

    Babaskin, D V

    2010-01-01

    The objective of the present study was to demonstrate the possibilities to analyse selected segments of the target market of physiotherapeutic services provided by medical and preventive-facilities of two major types. The main features of a target segment, such as provision of therapeutic massage, are illustrated in terms of two characteristics, namely attractiveness to the users and the ability of a given medical facility to satisfy their requirements. Based on the analysis of portfolio of the available target segments the most promising ones (winner segments) were selected for further marketing studies. This choice does not exclude the possibility of involvement of other segments of medical services in marketing activities.

  19. Factors associated with high probability of target blood pressure non-achievement in hypertensive patients

    Directory of Open Access Journals (Sweden)

    S. P. Zhemanyuk

    2017-12-01

    Full Text Available One of the topic issue of modern cardiology is factors of target blood pressure level non-achievement clarifying due to a better understanding how we can reduce cardiovascular complications. The aim of the study is to determine the factors of poor blood pressure control using the ambulatory blood pressure monitoring parameters and adenosine 5'-diphosphate-induced platelet aggregation parameters in patients with arterial hypertension. Material and methods. The study involved 153 patients with essential hypertension (EH stage II, II degree. The ambulatory blood pressure monitoring (ABPM was performed in patients during at least two of first-line antihypertensive drugs in optimal daily doses usage by the ABPM bifunctional device (Incart, S.-P., R.F.. Platelet aggregation was carried out using light transmittance aggregation by optical analyzer (Solar, R.B. with adenosine 5'-diphosphate (Sigma-Aldrich at final concentration of 10.0 × 10-6 mol / L. The first group were inadequately controlled essential hypertensive individuals with high systolic or/and diastolic BP level according to the ABPM results, and the second one were patients with adequately controlled EH. Groups of patients were comparable in age (60.39 ± 10.74 years vs. 62.80 ± 9.63; p = 0.181, respectively. In the group of EH patients who reached the target level of blood pressure, women predominated (60% vs. 39.81%; p = 0.021, respectively. We used the binary logistic regression analysis to determine the predictors of target blood pressure level poor reaching using ABPM and platelet aggregation parameters. Results According to the univariate logistic regression analysis, the dependent factors influencing the target blood pressure level poor reaching are the average diurnal diastolic blood pressure (DBP (OR = 44.8; diurnal variability of systolic blood pressure (SBP (OR = 4.4; square index of hypertension for diurnal periods SBP (OR = 318.9; square index of hypertension for diurnal

  20. Cell Penetrating Bispecific Antibodies for Targeting Oncogenic Transcription Factors in Advanced Prostate Cancer

    Science.gov (United States)

    2016-12-01

    Bispecific Antibodies for Targeting Oncogenic Transcription Factors in Advanced Prostate Cancer Michael Lilly, MD Richard Weisbart, MD Medical...0534, entitled Cell- penetrating bispecific antibodies for targeting oncogenic transcription factors in advanced prostate cancer . The research is a... Prostate cancer , antibody, bispecific, androgen receptor, castration-resistant 3

  1. Thermal-hydraulic analysis of PDS-XADS spallation target

    International Nuclear Information System (INIS)

    Ai Nisai; Yu Jiyang; Yang Yongwei

    2012-01-01

    This paper is a study of the thermal-hydraulic analysis of PDS-XADS spallation target for the large (80 MW) core concept. PDS-XADS is a small scale experimental accelerator driven sub-critical system (ADS). The analysis presented in this paper is based on lead bismuth eutectic (LBE) cooled XADS type experimental reactors, which are the de signs of the European experimental (PDS-XADS) project. The spallation target is a very important component of accelerator driven sub-critical system (ADS) because it is responsible to keep the reactor power at the required level by spallation reactions. A high rate of neutron production by spallation reaction creates the problem of decay heat cooling. LBE flow is properly cooled, but the window is not properly cooled because of the stagnation point in the pole of the window. It would be very difficult to keep the window temperature below the design limit, which is an important design limit challenge. Thermal-hydraulic analysis of LBE spallation target has been carried out by using ANSYS CFX 11.0. The detailed CFD analysis, which reveals thermal and hydraulic conditions in the window and spallation region, is carried out for different spallation target designs. Finally, the spallation target design limit is used to choose the best design. (authors)

  2. Analysis of target implosion irradiated by proton beam, (1)

    International Nuclear Information System (INIS)

    Tamba, Moritake; Nagata, Norimasa; Kawata, Shigeo; Niu, Keishiro.

    1982-10-01

    Numerical simulation and analysis were performed for the implosion of a hollow shell target driven by proton beam. The target consists of three layers of Pb, Al and DT. As the Al layer is heated by proton beam, the layer expands and pushes the DT layer toward the target center. To obtain the optimal velocity of DT implosion, the optimal target size and optimal layer thickness were determined. The target size is determined by, for example, the instability of the implosion or beam focusing on the target surface. The Rayleigh-Taylor instability and the unstable implosion due to the inhomogeneity were investigated. Dissipation, nonlinear effects and density gradient at the boundary were expected to reduce the growth rate of the Rayleigh-Taylor instability during the implosion. In order that the deviation of the boundary surface during the implosion is less than the thickness of fuel, the inhomogeneity of the temperature and the density of the target should be less than ten percent. The amplitude of the boundary surface roughness is required to be less than 4 micrometer. (Kato, T.)

  3. Conditions for factor (in)determinacy in factor analysis

    NARCIS (Netherlands)

    Krijnen, W.P.; Dijkstra, T.K.; Gill, R.D.

    1998-01-01

    The subject of factor indeterminacy has a vast history in factor analysis Wilson Lederman Guttman It has lead to strong dierences in opinion Steiger The current paper gives necessary and sucient conditions for observability of factors in terms of the parameter matrices and a nite number of

  4. Conditions for factor (in)determinacy in factor analysis

    NARCIS (Netherlands)

    Krijnen, W.P.; Dijkstra, T.K.; Gill, R.D.

    1998-01-01

    The subject of factor indeterminacy has a vast history in factor analysis (Guttman, 1955; Lederman, 1938; Wilson, 1928). It has lead to strong differences in opinion (Steiger, 1979). The current paper gives necessary and sufficient conditions for observability of factors in terms of the parameter

  5. Facility factors dominate the ability to achieve target haemoglobin levels in haemodialysis patients.

    Science.gov (United States)

    Chan, Kevin E; Lafayette, Richard A; Whittemore, Alice S; Hlatky, Mark A; Moran, John

    2008-09-01

    Our objective was to determine whether patient factors, processes of care and measures of erythropoietin (EPO) responsiveness were associated with successful anemia management at the individual patient level. We retrospectively reviewed laboratory and demographic data from 1499 patients receiving hemodialysis in 15 units operated by the same dialysis provider. We performed univariate and multivariate logistic regression analysis to determine predictors of an average 3-month hemoglobin level below or above the target interval of 11.0-12.5 g/dL. To explain the effect of facility on anemia performance, we calculated correlations between measures of EPO responsiveness and the probability of achieving the target interval by facility. Patients above the target hemoglobin range demonstrated an association with parathyroid hormone (PTH) (OR = 0.96 per 100 pg/mL increase), female gender (OR = 0.68), EPO protocol use (OR = 0.94 per 10% increase in use) and facility (range of OR = 0.26-2.59 for 15 participating sites). Patients below the target hemoglobin range demonstrated an association with CRP (OR = 1.10 per mg/L increase), PTH (OR = 1.07 per 100 pg/mL increase), iron deficiency (OR = 1.07 per 10% increase), EPO protocol use (OR = 0.89 per 10% increase in use), iron protocol use (OR = 0.93 per 10% increase in use) and facility (range of OR = 0.58-3.41 over 15 units). EPO index (r = 0.71), EPO dose (r = 0.73), hemoglobin (r = -0.60) and EPO per unit weight (r = 0.76) were significantly correlated with the probability of achieving the target hemoglobin by facility. The facility significantly influences the outcome of anemia management in patients with ESRD. In part, this is due to the patients' EPO responsiveness, which may be influenced by facility care patterns.

  6. Using Horn's Parallel Analysis Method in Exploratory Factor Analysis for Determining the Number of Factors

    Science.gov (United States)

    Çokluk, Ömay; Koçak, Duygu

    2016-01-01

    In this study, the number of factors obtained from parallel analysis, a method used for determining the number of factors in exploratory factor analysis, was compared to that of the factors obtained from eigenvalue and scree plot--two traditional methods for determining the number of factors--in terms of consistency. Parallel analysis is based on…

  7. Co-factors necessary for PPAR mediated transactivation of endogenous target genes

    DEFF Research Database (Denmark)

    Grøntved, Lars; Nielsen, Ronni; Stunnenberg, Henk

    of endogenous target gene in different cell types are elusive. To mutually compare the ability of the PPAR subtypes to activate endogenous target genes in a given cell, PPARa, PPARb/d and PPARg2 were HA tagged and rapidly, equally and synchronously expressed using adenoviral delivery. Within a few hours after...... subtype specific activation of target genes. Accumulating evidence suggests that transcriptional co-factors can function as master regulators for nuclear receptors and impose promoter selectivity. To study co-factor necessity for PPAR mediated transactivation of endogenous target genes, specific co...

  8. A factor analysis to detect factors influencing building national brand

    Directory of Open Access Journals (Sweden)

    Naser Azad

    Full Text Available Developing a national brand is one of the most important issues for development of a brand. In this study, we present factor analysis to detect the most important factors in building a national brand. The proposed study uses factor analysis to extract the most influencing factors and the sample size has been chosen from two major auto makers in Iran called Iran Khodro and Saipa. The questionnaire was designed in Likert scale and distributed among 235 experts. Cronbach alpha is calculated as 84%, which is well above the minimum desirable limit of 0.70. The implementation of factor analysis provides six factors including “cultural image of customers”, “exciting characteristics”, “competitive pricing strategies”, “perception image” and “previous perceptions”.

  9. Genome-wide analysis of Polycomb targets in Drosophila

    Energy Technology Data Exchange (ETDEWEB)

    Schwartz, Yuri B.; Kahn, Tatyana G.; Nix, David A.; Li,Xiao-Yong; Bourgon, Richard; Biggin, Mark; Pirrotta, Vincenzo

    2006-04-01

    Polycomb Group (PcG) complexes are multiprotein assemblages that bind to chromatin and establish chromatin states leading to epigenetic silencing. PcG proteins regulate homeotic genes in flies and vertebrates but little is known about other PcG targets and the role of the PcG in development, differentiation and disease. We have determined the distribution of the PcG proteins PC, E(Z) and PSC and of histone H3K27 trimethylation in the Drosophila genome. At more than 200 PcG target genes, binding sites for the three PcG proteins colocalize to presumptive Polycomb Response Elements (PREs). In contrast, H3 me3K27 forms broad domains including the entire transcription unit and regulatory regions. PcG targets are highly enriched in genes encoding transcription factors but receptors, signaling proteins, morphogens and regulators representing all major developmental pathways are also included.

  10. Targets for bulk hydrogen analysis using thermal neutrons

    CERN Document Server

    Csikai, J; Buczko, C M

    2002-01-01

    The reflection property of substances can be characterized by the reflection cross-section of thermal neutrons, sigma subbeta. A combination of the targets with thin polyethylene foils allowed an estimation of the flux depression of thermal neutrons caused by a bulk sample containing highly absorbing elements or compounds. Some new and more accurate sigma subbeta values were determined by using the combined target arrangement. For the ratio, R of the reflection and the elastic scattering cross-sections of thermal neutrons, R=sigma subbeta/sigma sub E sub L a value of 0.60+-0.02 was found on the basis of the data obtained for a number of elements from H to Pb. Using this correlation factor, and the sigma sub E sub L values, the unknown sigma subbeta data can be deduced. The equivalent thicknesses, to polyethylene or hydrogen, of the different target materials were determined from the sigma subbeta values.

  11. A mathematical analysis of multiple-target SELEX.

    Science.gov (United States)

    Seo, Yeon-Jung; Chen, Shiliang; Nilsen-Hamilton, Marit; Levine, Howard A

    2010-10-01

    SELEX (Systematic Evolution of Ligands by Exponential Enrichment) is a procedure by which a mixture of nucleic acids can be fractionated with the goal of identifying those with specific biochemical activities. One combines the mixture with a specific target molecule and then separates the target-NA complex from the resulting reactions. The target-NA complex is separated from the unbound NA by mechanical means (such as by filtration), the NA is eluted from the complex, amplified by PCR (polymerase chain reaction), and the process repeated. After several rounds, one should be left with the nucleic acids that best bind to the target. The problem was first formulated mathematically in Irvine et al. (J. Mol. Biol. 222:739-761, 1991). In Levine and Nilsen-Hamilton (Comput. Biol. Chem. 31:11-25, 2007), a mathematical analysis of the process was given. In Vant-Hull et al. (J. Mol. Biol. 278:579-597, 1998), multiple target SELEX was considered. It was assumed that each target has a single nucleic acid binding site that permits occupation by no more than one nucleic acid. Here, we revisit Vant-Hull et al. (J. Mol. Biol. 278:579-597, 1998) using the same assumptions. The iteration scheme is shown to be convergent and a simplified algorithm is given. Our interest here is in the behavior of the multiple target SELEX process as a discrete "time" dynamical system. Our goal is to characterize the limiting states and their dependence on the initial distribution of nucleic acid and target fraction components. (In multiple target SELEX, we vary the target component fractions, but not their concentrations, as fixed and the initial pool of nucleic acids as a variable starting condition). Given N nucleic acids and a target consisting of M subtarget component species, there is an M × N matrix of affinities, the (i,j) entry corresponding to the affinity of the jth nucleic acid for the ith subtarget. We give a structure condition on this matrix that is equivalent to the following

  12. Real Time Intelligent Target Detection and Analysis with Machine Vision

    Science.gov (United States)

    Howard, Ayanna; Padgett, Curtis; Brown, Kenneth

    2000-01-01

    We present an algorithm for detecting a specified set of targets for an Automatic Target Recognition (ATR) application. ATR involves processing images for detecting, classifying, and tracking targets embedded in a background scene. We address the problem of discriminating between targets and nontarget objects in a scene by evaluating 40x40 image blocks belonging to an image. Each image block is first projected onto a set of templates specifically designed to separate images of targets embedded in a typical background scene from those background images without targets. These filters are found using directed principal component analysis which maximally separates the two groups. The projected images are then clustered into one of n classes based on a minimum distance to a set of n cluster prototypes. These cluster prototypes have previously been identified using a modified clustering algorithm based on prior sensed data. Each projected image pattern is then fed into the associated cluster's trained neural network for classification. A detailed description of our algorithm will be given in this paper. We outline our methodology for designing the templates, describe our modified clustering algorithm, and provide details on the neural network classifiers. Evaluation of the overall algorithm demonstrates that our detection rates approach 96% with a false positive rate of less than 0.03%.

  13. Measurement Bias Detection through Factor Analysis

    Science.gov (United States)

    Barendse, M. T.; Oort, F. J.; Werner, C. S.; Ligtvoet, R.; Schermelleh-Engel, K.

    2012-01-01

    Measurement bias is defined as a violation of measurement invariance, which can be investigated through multigroup factor analysis (MGFA), by testing across-group differences in intercepts (uniform bias) and factor loadings (nonuniform bias). Restricted factor analysis (RFA) can also be used to detect measurement bias. To also enable nonuniform…

  14. The Infinitesimal Jackknife with Exploratory Factor Analysis

    Science.gov (United States)

    Zhang, Guangjian; Preacher, Kristopher J.; Jennrich, Robert I.

    2012-01-01

    The infinitesimal jackknife, a nonparametric method for estimating standard errors, has been used to obtain standard error estimates in covariance structure analysis. In this article, we adapt it for obtaining standard errors for rotated factor loadings and factor correlations in exploratory factor analysis with sample correlation matrices. Both…

  15. Penetration analysis of projectile with inclined concrete target

    Directory of Open Access Journals (Sweden)

    Kim S.B.

    2015-01-01

    Full Text Available This paper presents numerical analysis result of projectile penetration with concrete target. We applied dynamic material properties of 4340 steels, aluminium and explosive for projectile body. Dynamic material properties were measured with static tensile testing machine and Hopkinson pressure bar tests. Moreover, we used three concrete damage models included in LS-DYNA 3D, such as SOIL_CONCRETE, CSCM (cap model with smooth interaction and CONCRETE_DAMAGE (K&C concrete models. Strain rate effect for concrete material is important to predict the fracture deformation and shape of concrete, and penetration depth for projectiles. CONCRETE_DAMAGE model with strain rate effect also applied to penetration analysis. Analysis result with CSCM model shows good agreement with penetration experimental data. The projectile trace and fracture shapes of concrete target were compared with experimental data.

  16. Penetration analysis of projectile with inclined concrete target

    Science.gov (United States)

    Kim, S. B.; Kim, H. W.; Yoo, Y. H.

    2015-09-01

    This paper presents numerical analysis result of projectile penetration with concrete target. We applied dynamic material properties of 4340 steels, aluminium and explosive for projectile body. Dynamic material properties were measured with static tensile testing machine and Hopkinson pressure bar tests. Moreover, we used three concrete damage models included in LS-DYNA 3D, such as SOIL_CONCRETE, CSCM (cap model with smooth interaction) and CONCRETE_DAMAGE (K&C concrete) models. Strain rate effect for concrete material is important to predict the fracture deformation and shape of concrete, and penetration depth for projectiles. CONCRETE_DAMAGE model with strain rate effect also applied to penetration analysis. Analysis result with CSCM model shows good agreement with penetration experimental data. The projectile trace and fracture shapes of concrete target were compared with experimental data.

  17. c-Met in esophageal squamous cell carcinoma: an independent prognostic factor and potential therapeutic target

    International Nuclear Information System (INIS)

    Ozawa, Yohei; Nakamura, Yasuhiro; Fujishima, Fumiyoshi; Felizola, Saulo JA; Takeda, Kenichiro; Okamoto, Hiroshi; Ito, Ken; Ishida, Hirotaka; Konno, Takuro; Kamei, Takashi; Miyata, Go; Ohuchi, Noriaki; Sasano, Hironobu

    2015-01-01

    c-Met is widely known as a poor prognostic factor in various human malignancies. Previous studies have suggested the involvement of c-Met and/or its ligand, hepatocyte growth factor (HGF), in esophageal squamous cell carcinoma (ESCC), but the correlation between c-Met status and clinical outcome remains unclear. Furthermore, the identification of a novel molecular therapeutic target might potentially help improve the clinical outcome of ESCC patients. The expression of c-Met and HGF was immunohistochemically assessed in 104 surgically obtained tissue specimens. The correlation between c-Met/HGF expression and patients’ clinicopathological features, including survival, was evaluated. We also investigated changes in cell functions and protein expression of c-Met and its downstream signaling pathway components under treatments with HGF and/or c-Met inhibitor in ESCC cell lines. Elevated expression of c-Met was significantly correlated with tumor depth and pathological stage. Patients with high c-Met expression had significantly worse survival. In addition, multivariate analysis identified the high expression of c-Met as an independent prognostic factor. Treatment with c-Met inhibitor under HGF stimulation significantly inhibited the invasive capacity of an ESCC cell line with elevated c-Met mRNA expression. Moreover, c-Met and its downstream signaling inactivation was also detected after treatment with c-Met inhibitor. The results of our study identified c-Met expression as an independent prognostic factor in ESCC patients and demonstrated that c-Met could be a potential molecular therapeutic target for the treatment of ESCC with elevated c-Met expression. The online version of this article (doi:10.1186/s12885-015-1450-3) contains supplementary material, which is available to authorized users

  18. Physiological enhancement of factors in factor analysis of dynamic studies

    International Nuclear Information System (INIS)

    Samal, M.; Surova, H.; Marikova, E.; Michalova, K.; Karny, M.; Dienstbier, Z.

    1986-01-01

    Factor analysis of dynamic radionuclide studies provides their decomposition into the images and time-activity curves corresponding to the underlying dynamic structures. The method is based on the analysis of study variance and on the subsequent differential imaging of its principal components into a simplified factor space. By changing the amount and the composition of the variance processed in the analysis it is possible to enhance the factors that are important for diagnosis while the less important factors can be suppressed. In our report, a short theoretical review of the problem is given and illustrated by the analysis of dynamic cholescintigraphy. It is shown that a suitable choice of region and/or the temporal interval of interest enables the differential evaluation of such intrahepatic compartments, which could not be observed without enhancement. (orig.)

  19. Tissue factor is an angiogenic-specific receptor for factor VII-targeted immunotherapy and photodynamic therapy.

    Science.gov (United States)

    Hu, Zhiwei; Cheng, Jijun; Xu, Jie; Ruf, Wolfram; Lockwood, Charles J

    2017-02-01

    Identification of target molecules specific for angiogenic vascular endothelial cells (VEC), the inner layer of pathological neovasculature, is critical for discovery and development of neovascular-targeting therapy for angiogenesis-dependent human diseases, notably cancer, macular degeneration and endometriosis, in which vascular endothelial growth factor (VEGF) plays a central pathophysiological role. Using VEGF-stimulated vascular endothelial cells (VECs) isolated from microvessels, venous and arterial blood vessels as in vitro angiogenic models and unstimulated VECs as a quiescent VEC model, we examined the expression of tissue factor (TF), a membrane-bound receptor on the angiogenic VEC models compared with quiescent VEC controls. We found that TF is specifically expressed on angiogenic VECs in a time-dependent manner in microvessels, venous and arterial vessels. TF-targeted therapeutic agents, including factor VII (fVII)-IgG1 Fc and fVII-conjugated photosensitizer, can selectively bind angiogenic VECs, but not the quiescent VECs. Moreover, fVII-targeted photodynamic therapy can selectively and completely eradicate angiogenic VECs. We conclude that TF is an angiogenic-specific receptor and the target molecule for fVII-targeted therapeutics. This study supports clinical trials of TF-targeted therapeutics for the treatment of angiogenesis-dependent diseases such as cancer, macular degeneration and endometriosis.

  20. Integrative analysis to select cancer candidate biomarkers to targeted validation

    Science.gov (United States)

    Heberle, Henry; Domingues, Romênia R.; Granato, Daniela C.; Yokoo, Sami; Canevarolo, Rafael R.; Winck, Flavia V.; Ribeiro, Ana Carolina P.; Brandão, Thaís Bianca; Filgueiras, Paulo R.; Cruz, Karen S. P.; Barbuto, José Alexandre; Poppi, Ronei J.; Minghim, Rosane; Telles, Guilherme P.; Fonseca, Felipe Paiva; Fox, Jay W.; Santos-Silva, Alan R.; Coletta, Ricardo D.; Sherman, Nicholas E.; Paes Leme, Adriana F.

    2015-01-01

    Targeted proteomics has flourished as the method of choice for prospecting for and validating potential candidate biomarkers in many diseases. However, challenges still remain due to the lack of standardized routines that can prioritize a limited number of proteins to be further validated in human samples. To help researchers identify candidate biomarkers that best characterize their samples under study, a well-designed integrative analysis pipeline, comprising MS-based discovery, feature selection methods, clustering techniques, bioinformatic analyses and targeted approaches was performed using discovery-based proteomic data from the secretomes of three classes of human cell lines (carcinoma, melanoma and non-cancerous). Three feature selection algorithms, namely, Beta-binomial, Nearest Shrunken Centroids (NSC), and Support Vector Machine-Recursive Features Elimination (SVM-RFE), indicated a panel of 137 candidate biomarkers for carcinoma and 271 for melanoma, which were differentially abundant between the tumor classes. We further tested the strength of the pipeline in selecting candidate biomarkers by immunoblotting, human tissue microarrays, label-free targeted MS and functional experiments. In conclusion, the proposed integrative analysis was able to pre-qualify and prioritize candidate biomarkers from discovery-based proteomics to targeted MS. PMID:26540631

  1. Transcriptome Analysis of Targeted Mouse Mutations Reveals the Topography of Local Changes in Gene Expression.

    Directory of Open Access Journals (Sweden)

    David B West

    2016-02-01

    Full Text Available The unintended consequences of gene targeting in mouse models have not been thoroughly studied and a more systematic analysis is needed to understand the frequency and characteristics of off-target effects. Using RNA-seq, we evaluated targeted and neighboring gene expression in tissues from 44 homozygous mutants compared with C57BL/6N control mice. Two allele types were evaluated: 15 targeted trap mutations (TRAP; and 29 deletion alleles (DEL, usually a deletion between the translational start and the 3' UTR. Both targeting strategies insert a bacterial beta-galactosidase reporter (LacZ and a neomycin resistance selection cassette. Evaluating transcription of genes in +/- 500 kb of flanking DNA around the targeted gene, we found up-regulated genes more frequently around DEL compared with TRAP alleles, however the frequency of alleles with local down-regulated genes flanking DEL and TRAP targets was similar. Down-regulated genes around both DEL and TRAP targets were found at a higher frequency than expected from a genome-wide survey. However, only around DEL targets were up-regulated genes found with a significantly higher frequency compared with genome-wide sampling. Transcriptome analysis confirms targeting in 97% of DEL alleles, but in only 47% of TRAP alleles probably due to non-functional splice variants, and some splicing around the gene trap. Local effects on gene expression are likely due to a number of factors including compensatory regulation, loss or disruption of intragenic regulatory elements, the exogenous promoter in the neo selection cassette, removal of insulating DNA in the DEL mutants, and local silencing due to disruption of normal chromatin organization or presence of exogenous DNA. An understanding of local position effects is important for understanding and interpreting any phenotype attributed to targeted gene mutations, or to spontaneous indels.

  2. TARGET - TASK ANALYSIS REPORT GENERATION TOOL, VERSION 1.0

    Science.gov (United States)

    Ortiz, C. J.

    1994-01-01

    The Task Analysis Report Generation Tool, TARGET, is a graphical interface tool used to capture procedural knowledge and translate that knowledge into a hierarchical report. TARGET is based on VISTA, a knowledge acquisition tool developed by the Naval Systems Training Center. TARGET assists a programmer and/or task expert organize and understand the steps involved in accomplishing a task. The user can label individual steps in the task through a dialogue-box and get immediate graphical feedback for analysis. TARGET users can decompose tasks into basic action kernels or minimal steps to provide a clear picture of all basic actions needed to accomplish a job. This method allows the user to go back and critically examine the overall flow and makeup of the process. The user can switch between graphics (box flow diagrams) and text (task hierarchy) versions to more easily study the process being documented. As the practice of decomposition continues, tasks and their subtasks can be continually modified to more accurately reflect the user's procedures and rationale. This program is designed to help a programmer document an expert's task thus allowing the programmer to build an expert system which can help others perform the task. Flexibility is a key element of the system design and of the knowledge acquisition session. If the expert is not able to find time to work on the knowledge acquisition process with the program developer, the developer and subject matter expert may work in iterative sessions. TARGET is easy to use and is tailored to accommodate users ranging from the novice to the experienced expert systems builder. TARGET is written in C-language for IBM PC series and compatible computers running MS-DOS and Microsoft Windows version 3.0 or 3.1. No source code is supplied. The executable also requires 2Mb of RAM, a Microsoft compatible mouse, a VGA display and an 80286, 386 or 486 processor machine. The standard distribution medium for TARGET is one 5.25 inch 360K

  3. Maximum auto-mutual-information factor analysis

    DEFF Research Database (Denmark)

    Nielsen, Allan Aasbjerg

    2017-01-01

    Based on the information theoretical measure mutual information derived from entropy and Kullback-Leibler divergence, an alternative to maximum autocorrelation factor analysis is sketched.......Based on the information theoretical measure mutual information derived from entropy and Kullback-Leibler divergence, an alternative to maximum autocorrelation factor analysis is sketched....

  4. Bioinformatics analysis of Brucella vaccines and vaccine targets using VIOLIN.

    Science.gov (United States)

    He, Yongqun; Xiang, Zuoshuang

    2010-09-27

    Brucella spp. are Gram-negative, facultative intracellular bacteria that cause brucellosis, one of the commonest zoonotic diseases found worldwide in humans and a variety of animal species. While several animal vaccines are available, there is no effective and safe vaccine for prevention of brucellosis in humans. VIOLIN (http://www.violinet.org) is a web-based vaccine database and analysis system that curates, stores, and analyzes published data of commercialized vaccines, and vaccines in clinical trials or in research. VIOLIN contains information for 454 vaccines or vaccine candidates for 73 pathogens. VIOLIN also contains many bioinformatics tools for vaccine data analysis, data integration, and vaccine target prediction. To demonstrate the applicability of VIOLIN for vaccine research, VIOLIN was used for bioinformatics analysis of existing Brucella vaccines and prediction of new Brucella vaccine targets. VIOLIN contains many literature mining programs (e.g., Vaxmesh) that provide in-depth analysis of Brucella vaccine literature. As a result of manual literature curation, VIOLIN contains information for 38 Brucella vaccines or vaccine candidates, 14 protective Brucella antigens, and 68 host response studies to Brucella vaccines from 97 peer-reviewed articles. These Brucella vaccines are classified in the Vaccine Ontology (VO) system and used for different ontological applications. The web-based VIOLIN vaccine target prediction program Vaxign was used to predict new Brucella vaccine targets. Vaxign identified 14 outer membrane proteins that are conserved in six virulent strains from B. abortus, B. melitensis, and B. suis that are pathogenic in humans. Of the 14 membrane proteins, two proteins (Omp2b and Omp31-1) are not present in B. ovis, a Brucella species that is not pathogenic in humans. Brucella vaccine data stored in VIOLIN were compared and analyzed using the VIOLIN query system. Bioinformatics curation and ontological representation of Brucella vaccines

  5. Bioinformatics analysis of Brucella vaccines and vaccine targets using VIOLIN

    Science.gov (United States)

    2010-01-01

    Background Brucella spp. are Gram-negative, facultative intracellular bacteria that cause brucellosis, one of the commonest zoonotic diseases found worldwide in humans and a variety of animal species. While several animal vaccines are available, there is no effective and safe vaccine for prevention of brucellosis in humans. VIOLIN (http://www.violinet.org) is a web-based vaccine database and analysis system that curates, stores, and analyzes published data of commercialized vaccines, and vaccines in clinical trials or in research. VIOLIN contains information for 454 vaccines or vaccine candidates for 73 pathogens. VIOLIN also contains many bioinformatics tools for vaccine data analysis, data integration, and vaccine target prediction. To demonstrate the applicability of VIOLIN for vaccine research, VIOLIN was used for bioinformatics analysis of existing Brucella vaccines and prediction of new Brucella vaccine targets. Results VIOLIN contains many literature mining programs (e.g., Vaxmesh) that provide in-depth analysis of Brucella vaccine literature. As a result of manual literature curation, VIOLIN contains information for 38 Brucella vaccines or vaccine candidates, 14 protective Brucella antigens, and 68 host response studies to Brucella vaccines from 97 peer-reviewed articles. These Brucella vaccines are classified in the Vaccine Ontology (VO) system and used for different ontological applications. The web-based VIOLIN vaccine target prediction program Vaxign was used to predict new Brucella vaccine targets. Vaxign identified 14 outer membrane proteins that are conserved in six virulent strains from B. abortus, B. melitensis, and B. suis that are pathogenic in humans. Of the 14 membrane proteins, two proteins (Omp2b and Omp31-1) are not present in B. ovis, a Brucella species that is not pathogenic in humans. Brucella vaccine data stored in VIOLIN were compared and analyzed using the VIOLIN query system. Conclusions Bioinformatics curation and ontological

  6. Full-Information Item Factor Analysis.

    Science.gov (United States)

    Bock, R. Darrell; And Others

    1988-01-01

    A method of item factor analysis is described, which is based on Thurstone's multiple-factor model and implemented by marginal maximum likelihood estimation and the EM algorithm. Also assessed are the statistical significance of successive factors added to the model, provisions for guessing and omitted items, and Bayes constraints. (TJH)

  7. Neighborhood Regularized Logistic Matrix Factorization for Drug-Target Interaction Prediction.

    Directory of Open Access Journals (Sweden)

    Yong Liu

    2016-02-01

    Full Text Available In pharmaceutical sciences, a crucial step of the drug discovery process is the identification of drug-target interactions. However, only a small portion of the drug-target interactions have been experimentally validated, as the experimental validation is laborious and costly. To improve the drug discovery efficiency, there is a great need for the development of accurate computational approaches that can predict potential drug-target interactions to direct the experimental verification. In this paper, we propose a novel drug-target interaction prediction algorithm, namely neighborhood regularized logistic matrix factorization (NRLMF. Specifically, the proposed NRLMF method focuses on modeling the probability that a drug would interact with a target by logistic matrix factorization, where the properties of drugs and targets are represented by drug-specific and target-specific latent vectors, respectively. Moreover, NRLMF assigns higher importance levels to positive observations (i.e., the observed interacting drug-target pairs than negative observations (i.e., the unknown pairs. Because the positive observations are already experimentally verified, they are usually more trustworthy. Furthermore, the local structure of the drug-target interaction data has also been exploited via neighborhood regularization to achieve better prediction accuracy. We conducted extensive experiments over four benchmark datasets, and NRLMF demonstrated its effectiveness compared with five state-of-the-art approaches.

  8. Neighborhood Regularized Logistic Matrix Factorization for Drug-Target Interaction Prediction.

    Science.gov (United States)

    Liu, Yong; Wu, Min; Miao, Chunyan; Zhao, Peilin; Li, Xiao-Li

    2016-02-01

    In pharmaceutical sciences, a crucial step of the drug discovery process is the identification of drug-target interactions. However, only a small portion of the drug-target interactions have been experimentally validated, as the experimental validation is laborious and costly. To improve the drug discovery efficiency, there is a great need for the development of accurate computational approaches that can predict potential drug-target interactions to direct the experimental verification. In this paper, we propose a novel drug-target interaction prediction algorithm, namely neighborhood regularized logistic matrix factorization (NRLMF). Specifically, the proposed NRLMF method focuses on modeling the probability that a drug would interact with a target by logistic matrix factorization, where the properties of drugs and targets are represented by drug-specific and target-specific latent vectors, respectively. Moreover, NRLMF assigns higher importance levels to positive observations (i.e., the observed interacting drug-target pairs) than negative observations (i.e., the unknown pairs). Because the positive observations are already experimentally verified, they are usually more trustworthy. Furthermore, the local structure of the drug-target interaction data has also been exploited via neighborhood regularization to achieve better prediction accuracy. We conducted extensive experiments over four benchmark datasets, and NRLMF demonstrated its effectiveness compared with five state-of-the-art approaches.

  9. Analysis of Myc-induced histone modifications on target chromatin.

    Directory of Open Access Journals (Sweden)

    Francesca Martinato

    Full Text Available The c-myc proto-oncogene is induced by mitogens and is a central regulator of cell growth and differentiation. The c-myc product, Myc, is a transcription factor that binds a multitude of genomic sites, estimated to be over 10-15% of all promoter regions. Target promoters generally pre-exist in an active or poised chromatin state that is further modified by Myc, contributing to fine transcriptional regulation (activation or repression of the afferent gene. Among other mechanisms, Myc recruits histone acetyl-transferases to target chromatin and locally promotes hyper-acetylation of multiple lysines on histones H3 and H4, although the identity and combination of the modified lysines is unknown. Whether Myc dynamically regulates other histone modifications (or marks at its binding sites also remains to be addressed. Here, we used quantitative chromatin immunoprecipitation (qChIP to profile a total of 24 lysine-acetylation and -methylation marks modulated by Myc at target promoters in a human B-cell line with a regulatable c-myc transgene. Myc binding promoted acetylation of multiple lysines, primarily of H3K9, H3K14, H3K18, H4K5 and H4K12, but significantly also of H4K8, H4K91 and H2AK5. Dimethylation of H3K79 was also selectively induced at target promoters. A majority of target promoters showed co-induction of multiple marks - in various combinations - correlating with recruitment of the two HATs tested (Tip60 and HBO1, incorporation of the histone variant H2A.Z and transcriptional activation. Based on this and previous findings, we surmise that Myc recruits the Tip60/p400 complex to achieve a coordinated histone acetylation/exchange reaction at activated promoters. Our data are also consistent with the additive and redundant role of multiple acetylation events in transcriptional activation.

  10. Applications of time-frequency signature analysis to target identification

    Science.gov (United States)

    Gaunaurd, Guillermo C.; Strifors, Hans C.

    1999-03-01

    The overlapping subjects of target identification, inverse scattering and active classification have many applications that differ depending on specific sensors. Many useful techniques for these relevant subjects have been developed in the frequency and the time domains. A more recent approach views the target signatures in the combined or coupled time-frequency domain. For either ultra-wideband (UWB) projectors, or UWB processing these joint time- frequency techniques are particularly advantageous. Such analysis requires the use of some of the scores of non- linear distributions that have been proposed and studied over the years. Basic ones, such as the Wigner distribution and its many relatives, have been shown to belong to the well-studied `Cohen Class.' We will select half-a-dozen of these distributions to study applications that we have addressed and solved in several areas such as: (1) active sonar, (2) underwater mine classification using pulses from explosive sources, (3) identification of submerged shells having different fillers using dolphin bio-sonar `clicks,' and (4) broadband radar pulses to identify aircraft, other targets covered with dielectric absorbing layers, and also (land) mine-like objects buried underground, using a ground penetrating radar. These examples illustrate how the informative identifying features required for accurate target identification are extracted and displayed in this general time-frequency domain.

  11. Discriminatory Analysis II. Factor Analysis and Discrimination

    Science.gov (United States)

    1950-10-01

    19L8. The dependence of factorial composition • o aptitude teaLs upon populatioxn differences among pilot trainees: I._The isola.tion of factors...per- formaneqe tests. J. Appl. Psych., 27, 135-149. - -. . 9J7_. _The graduate r~cord examination vs. other measures of aptitude and achievement. Ed...34 Psyoh. X~asef 5, 241 -26O. ¾ __l~iY anaysi oa dsrete re’spo’ns~es to the- Rorschach ink blots. -. J, Cons.,.Psyci.,, 13, 335񓵨* and/ Lars en, R-P 1

  12. Dissecting the signaling events that impact classical nuclear import and target nuclear transport factors.

    Directory of Open Access Journals (Sweden)

    Mohamed Kodiha

    2009-12-01

    Full Text Available Signaling through MEK-->ERK1/2 and PI3 kinases is implicated in many aspects of cell physiology, including the survival of oxidant exposure. Oxidants play a role in numerous physiological and pathophysiological processes, many of which rely on transport in and out of the nucleus. However, how oxidative stress impacts nuclear trafficking is not well defined.To better understand the effect of stress on nucleocytoplasmic trafficking, we exposed cells to the oxidant diethyl maleate. This treatment activated MEK-->ERK1/2 as well as PI3 kinase-->Akt cascades and triggered the inhibition of classical nuclear import. To define the molecular mechanisms that regulate nuclear transport, we examined whether MEK and PI3 kinase signaling affected the localization of key transport factors. Using recently developed tools for image acquisition and analysis, the subcellular distributions of importin-alpha, CAS, and nucleoporins Nup153 and Nup88 were quantified in different cellular compartments. These studies identified specific profiles for the localization of transport factors in the nucleus and cytoplasm, and at the nuclear envelope. Our results demonstrate that MEK and PI3 kinase signaling as well as oxidative stress control nuclear trafficking and the localization of transport components. Furthermore, stress not only induced changes in transport factor distribution, but also upregulated post-translational modification of transport factors. Our results are consistent with the idea that the phosphorylation of importin-alpha, CAS, Nup153, and Nup88, and the O-GlcNAc modification of Nup153 increase when cells are exposed to oxidant.Our studies defined the complex regulation of classical nuclear import and identified key transport factors that are targeted by stress, MEK, and PI3 kinase signaling.

  13. Identifying radiotherapy target volumes in brain cancer by image analysis.

    Science.gov (United States)

    Cheng, Kun; Montgomery, Dean; Feng, Yang; Steel, Robin; Liao, Hanqing; McLaren, Duncan B; Erridge, Sara C; McLaughlin, Stephen; Nailon, William H

    2015-10-01

    To establish the optimal radiotherapy fields for treating brain cancer patients, the tumour volume is often outlined on magnetic resonance (MR) images, where the tumour is clearly visible, and mapped onto computerised tomography images used for radiotherapy planning. This process requires considerable clinical experience and is time consuming, which will continue to increase as more complex image sequences are used in this process. Here, the potential of image analysis techniques for automatically identifying the radiation target volume on MR images, and thereby assisting clinicians with this difficult task, was investigated. A gradient-based level set approach was applied on the MR images of five patients with grades II, III and IV malignant cerebral glioma. The relationship between the target volumes produced by image analysis and those produced by a radiation oncologist was also investigated. The contours produced by image analysis were compared with the contours produced by an oncologist and used for treatment. In 93% of cases, the Dice similarity coefficient was found to be between 60 and 80%. This feasibility study demonstrates that image analysis has the potential for automatic outlining in the management of brain cancer patients, however, more testing and validation on a much larger patient cohort is required.

  14. SPATIAL ANALYSIS TO SUPPORT GEOGRAPHIC TARGETING OF GENOTYPES TO ENVIRONMENTS

    Directory of Open Access Journals (Sweden)

    Glenn eHyman

    2013-03-01

    Full Text Available Crop improvement efforts have benefited greatly from advances in available data, computing technology and methods for targeting genotypes to environments. These advances support the analysis of genotype by environment interactions to understand how well a genotype adapts to environmental conditions. This paper reviews the use of spatial analysis to support crop improvement research aimed at matching genotypes to their most appropriate environmental niches. Better data sets are now available on soils, weather and climate, elevation, vegetation, crop distribution and local conditions where genotypes are tested in experimental trial sites. The improved data are now combined with spatial analysis methods to compare environmental conditions across sites, create agro-ecological region maps and assess environment change. Climate, elevation and vegetation data sets are now widely available, supporting analyses that were much more difficult even five or ten years ago. While detailed soil data for many parts of the world remains difficult to acquire for crop improvement studies, new advances in digital soil mapping are likely to improve our capacity. Site analysis and matching and regional targeting methods have advanced in parallel to data and technology improvements. All these developments have increased our capacity to link genotype to phenotype and point to a vast potential to improve crop adaptation efforts.

  15. A mechanistic overview of herbal medicine and botanical compounds to target transcriptional factors in Breast cancer.

    Science.gov (United States)

    Zhao, Yingke; Liu, Yue

    2018-04-01

    The abnormalities of transcription factors, such as NF-κB, STAT, estrogen receptor, play a critical role in the initiation and progression of breast cancer. Due to the limitation of current treatment, transcription factors could be promising therapeutic targets, which have received close attention. In this review, we introduced herbal medicines, as well as botanical compounds that had been verified with anti-tumor properties via regulating transcription factors. Herbs, compounds, as well as formulae reported with various transcriptional targets, were summarized thoroughly, to provide implication for the future research on basic experiment and clinical application. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Genome-wide identification of Bcl11b gene targets reveals role in brain-derived neurotrophic factor signaling.

    Directory of Open Access Journals (Sweden)

    Bin Tang

    Full Text Available B-cell leukemia/lymphoma 11B (Bcl11b is a transcription factor showing predominant expression in the striatum. To date, there are no known gene targets of Bcl11b in the nervous system. Here, we define targets for Bcl11b in striatal cells by performing chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq in combination with genome-wide expression profiling. Transcriptome-wide analysis revealed that 694 genes were significantly altered in striatal cells over-expressing Bcl11b, including genes showing striatal-enriched expression similar to Bcl11b. ChIP-seq analysis demonstrated that Bcl11b bound a mixture of coding and non-coding sequences that were within 10 kb of the transcription start site of an annotated gene. Integrating all ChIP-seq hits with the microarray expression data, 248 direct targets of Bcl11b were identified. Functional analysis on the integrated gene target list identified several zinc-finger encoding genes as Bcl11b targets, and further revealed a significant association of Bcl11b to brain-derived neurotrophic factor/neurotrophin signaling. Analysis of ChIP-seq binding regions revealed significant consensus DNA binding motifs for Bcl11b. These data implicate Bcl11b as a novel regulator of the BDNF signaling pathway, which is disrupted in many neurological disorders. Specific targeting of the Bcl11b-DNA interaction could represent a novel therapeutic approach to lowering BDNF signaling specifically in striatal cells.

  17. Supervised non-negative tensor factorization for automatic hyperspectral feature extraction and target discrimination

    Science.gov (United States)

    Anderson, Dylan; Bapst, Aleksander; Coon, Joshua; Pung, Aaron; Kudenov, Michael

    2017-05-01

    Hyperspectral imaging provides a highly discriminative and powerful signature for target detection and discrimination. Recent literature has shown that considering additional target characteristics, such as spatial or temporal profiles, simultaneously with spectral content can greatly increase classifier performance. Considering these additional characteristics in a traditional discriminative algorithm requires a feature extraction step be performed first. An example of such a pipeline is computing a filter bank response to extract spatial features followed by a support vector machine (SVM) to discriminate between targets. This decoupling between feature extraction and target discrimination yields features that are suboptimal for discrimination, reducing performance. This performance reduction is especially pronounced when the number of features or available data is limited. In this paper, we propose the use of Supervised Nonnegative Tensor Factorization (SNTF) to jointly perform feature extraction and target discrimination over hyperspectral data products. SNTF learns a tensor factorization and a classification boundary from labeled training data simultaneously. This ensures that the features learned via tensor factorization are optimal for both summarizing the input data and separating the targets of interest. Practical considerations for applying SNTF to hyperspectral data are presented, and results from this framework are compared to decoupled feature extraction/target discrimination pipelines.

  18. Transcription factor HBP1 is a direct anti-cancer target of transcription factor FOXO1 in invasive oral cancer.

    Science.gov (United States)

    Chan, Chien-Yi; Huang, Shih-Yi; Sheu, Jim Jinn-Chyuan; Roth, Mendel M; Chou, I-Tai; Lien, Chia-Hsien; Lee, Ming-Fen; Huang, Chun-Yin

    2017-02-28

    Either FOXO1 or HBP1 transcription factor is a downstream effector of the PI3K/Akt pathway and associated with tumorigenesis. However, the relationship between FOXO1 and HBP1 in oral cancer remains unclear. Analysis of 30 oral tumor specimens revealed that mean mRNA levels of both FOXO1 and HBP1 in non-invasive and invasive oral tumors were found to be significantly lower than that of the control tissues, and the status of low FOXO1 and HBP1 (oral tumors. To investigate if HBP1 is a direct transcription target of FOXO1, we searched potential FOXO1 binding sites in the HBP1 promoter using the MAPPER Search Engine, and two putative FOXO1 binding sites located in the HBP1 promoter -132 to -125 bp and -343 to -336 bp were predicted. These binding sites were then confirmed by both reporter gene assays and the in cellulo ChIP assay. In addition, Akt activity manipulated by PI3K inhibitor LY294002 or Akt mutants was shown to negatively affect FOXO1-mediated HBP1 promoter activation and gene expression. Last, the biological significance of the FOXO1-HBP1 axis in oral cancer malignancy was evaluated in cell growth, colony formation, and invasiveness. The results indicated that HBP1 knockdown potently promoted malignant phenotypes of oral cancer and the suppressive effect of FOXO1 on cell growth, colony formation, and invasion was alleviated upon HBP1 knockdown in invasive oral cancer cells. Taken together, our data provide evidence for HBP1 as a direct downstream target of FOXO1 in oral cancer malignancy.

  19. Multiple factor analysis by example using R

    CERN Document Server

    Pagès, Jérôme

    2014-01-01

    Multiple factor analysis (MFA) enables users to analyze tables of individuals and variables in which the variables are structured into quantitative, qualitative, or mixed groups. Written by the co-developer of this methodology, Multiple Factor Analysis by Example Using R brings together the theoretical and methodological aspects of MFA. It also includes examples of applications and details of how to implement MFA using an R package (FactoMineR).The first two chapters cover the basic factorial analysis methods of principal component analysis (PCA) and multiple correspondence analysis (MCA). The

  20. Stakeholder analysis and mapping as targeted communication strategy.

    Science.gov (United States)

    Shirey, Maria R

    2012-09-01

    This department highlights change management strategies that may be successful in strategically planning and executing organizational change initiatives. With the goal of presenting practical approaches helpful to nurse leaders advancing organizational change, content includes evidence-based projects, tools, and resources that mobilize and sustain organizational change initiatives. In this article, the author highlights the importance of stakeholder theory and discusses how to apply the theory to conduct a stakeholder analysis. This article also provides an explanation of how to use related stakeholder mapping techniques with targeted communication strategies.

  1. Transcription factor Fos-related antigen 1 is an effective target for a breast cancer vaccine

    Science.gov (United States)

    Luo, Yunping; Zhou, He; Mizutani, Masato; Mizutani, Noriko; Reisfeld, Ralph A.; Xiang, Rong

    2003-07-01

    Protection against breast cancer was achieved with a DNA vaccine against murine transcription factor Fos-related antigen 1, which is overexpressed in aggressively proliferating D2F2 murine breast carcinoma. Growth of primary s.c. tumor and dissemination of pulmonary metastases was markedly suppressed by this oral DNA vaccine, carried by attenuated Salmonella typhimurium, encoding murine Fos-related antigen 1, fused with mutant polyubiquitin, and cotransformed with secretory murine IL-18. The life span of 60% of vaccinated mice was tripled in the absence of detectable tumor growth after lethal tumor cell challenge. Immunological mechanisms involved activation of T, natural killer, and dendritic cells, as indicated by up-regulation of their activation markers and costimulatory molecules. Markedly increased specific target cell lysis was mediated by both MHC class I-restricted CD8+ T cells and natural killer cells isolated from splenocytes of vaccinated mice, including a significant release of proinflammatory cytokines IFN- and IL-2. Importantly, fluorescence analysis of fibroblast growth factor 2 and tumor cell-induced vessel growth in Matrigel plugs demonstrated marked suppression of angiogenesis only in vaccinated animals. Taken together, this multifunctional DNA vaccine proved effective in protecting against growth and metastases of breast cancer by combining the action of immune effector cells with suppression of tumor angiogenesis. vaccine | tumor | metastases | antiangiogenesis

  2. Ideal MHD stability analysis of KSTAR target AT mode

    International Nuclear Information System (INIS)

    Yi, S.M.; Kim, J.H.; You, K.I.; Kim, J.Y.

    2009-01-01

    Full text: A main research objective of KSTAR (Korea Superconducting Tokamak Advanced Research) device is to demonstrate the steady-state operation capability of high-performance AT (Advanced Tokamak) mode. To meet this goal, it is critical for KSTAR to have a good MHD stability boundary, particularly against the high-beta ideal instabilities such as the external kink and the ballooning modes. To support this MHD stability KSTAR has been designed to have a strong plasma shape and a close interval between plasma and passive- plate wall. During the conceptual design phase of KSTAR, a preliminary study was performed to estimate the high beta MHD stability limit of KSTAR target AT mode using PEST and VACUUM codes and it was shown that the target AT mode can be stable up to β N ∼ 5 with a well-defined plasma pressure and current profiles. Recently, a new calculation has been performed to estimate the ideal stability limit in various KSTAR operating conditions using DCON code, and it has been observed that there is some difference between the new and old calculation results, particularly in the dependence of the maximum β N value on the toroidal mode number. Here, we thus present a more detailed analysis of the ideal MHD stability limit of KSTAR target AT mode using various codes, which include GATO as well as PEST and DCON, in the comparison of calculation results among the three codes. (author)

  3. Hypoxia-Independent Downregulation of Hypoxia-Inducible Factor 1 Targets by Androgen Deprivation Therapy in Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ragnum, Harald Bull [Department of Radiation Biology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo (Norway); Røe, Kathrine [Department of Radiation Biology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo (Norway); Division of Medicine, Department of Oncology, Akershus University Hospital, Lørenskog (Norway); Holm, Ruth; Vlatkovic, Ljiljana [Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo (Norway); Nesland, Jahn Marthin [Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo (Norway); Medical Faculty, University of Oslo, Oslo (Norway); Aarnes, Eva-Katrine [Department of Radiation Biology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo (Norway); Ree, Anne Hansen [Division of Medicine, Department of Oncology, Akershus University Hospital, Lørenskog (Norway); Medical Faculty, University of Oslo, Oslo (Norway); Flatmark, Kjersti [Department of Tumor Biology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo (Norway); Department of Gastrointestinal Surgery, The Norwegian Radium Hospital, Oslo University Hospital, Oslo (Norway); Seierstad, Therese [Department of Radiology and Nuclear Medicine, The Norwegian Radium Hospital, Oslo University Hospital, Oslo (Norway); Faculty of Health Sciences, Buskerud University College, Drammen (Norway); Lilleby, Wolfgang [Department of Oncology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo (Norway); Lyng, Heidi, E-mail: heidi.lyng@rr-research.no [Department of Radiation Biology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo (Norway)

    2013-11-15

    Purpose: We explored changes in hypoxia-inducible factor 1 (HIF1) signaling during androgen deprivation therapy (ADT) of androgen-sensitive prostate cancer xenografts under conditions in which no significant change in immunostaining of the hypoxia marker pimonidazole had occurred. Methods and Materials: Gene expression profiles of volume-matched androgen-exposed and androgen-deprived CWR22 xenografts, with similar pimonidazole-positive fractions, were compared. Direct targets of androgen receptor (AR) and HIF1 transcription factors were identified among the differentially expressed genes by using published lists. Biological processes affected by ADT were determined by gene ontology analysis. HIF1α protein expression in xenografts and biopsy samples from 35 patients receiving neoadjuvant ADT was assessed by immunohistochemistry. Results: A total of 1344 genes showed more than 2-fold change in expression by ADT, including 35 downregulated and 5 upregulated HIF1 targets. Six genes were shared HIF1 and AR targets, and their downregulation was confirmed with quantitative RT-PCR. Significant suppression of the biological processes proliferation, metabolism, and stress response in androgen-deprived xenografts was found, consistent with tumor regression. Nineteen downregulated HIF1 targets were involved in those significant biological processes, most of them in metabolism. Four of these were shared AR and HIF1 targets, including genes encoding the regulatory glycolytic proteins HK2, PFKFB3, and SLC2A1. Most of the downregulated HIF1 targets were induced by hypoxia in androgen-responsive prostate cancer cell lines, confirming their role as hypoxia-responsive HIF1 targets in prostate cancer. Downregulation of HIF1 targets was consistent with the absence of HIF1α protein in xenografts and downregulation in patients by ADT (P<.001). Conclusions: AR repression by ADT may lead to downregulation of HIF1 signaling independently of hypoxic fraction, and this may contribute to

  4. Hypoxia-Independent Downregulation of Hypoxia-Inducible Factor 1 Targets by Androgen Deprivation Therapy in Prostate Cancer

    International Nuclear Information System (INIS)

    Ragnum, Harald Bull; Røe, Kathrine; Holm, Ruth; Vlatkovic, Ljiljana; Nesland, Jahn Marthin; Aarnes, Eva-Katrine; Ree, Anne Hansen; Flatmark, Kjersti; Seierstad, Therese; Lilleby, Wolfgang; Lyng, Heidi

    2013-01-01

    Purpose: We explored changes in hypoxia-inducible factor 1 (HIF1) signaling during androgen deprivation therapy (ADT) of androgen-sensitive prostate cancer xenografts under conditions in which no significant change in immunostaining of the hypoxia marker pimonidazole had occurred. Methods and Materials: Gene expression profiles of volume-matched androgen-exposed and androgen-deprived CWR22 xenografts, with similar pimonidazole-positive fractions, were compared. Direct targets of androgen receptor (AR) and HIF1 transcription factors were identified among the differentially expressed genes by using published lists. Biological processes affected by ADT were determined by gene ontology analysis. HIF1α protein expression in xenografts and biopsy samples from 35 patients receiving neoadjuvant ADT was assessed by immunohistochemistry. Results: A total of 1344 genes showed more than 2-fold change in expression by ADT, including 35 downregulated and 5 upregulated HIF1 targets. Six genes were shared HIF1 and AR targets, and their downregulation was confirmed with quantitative RT-PCR. Significant suppression of the biological processes proliferation, metabolism, and stress response in androgen-deprived xenografts was found, consistent with tumor regression. Nineteen downregulated HIF1 targets were involved in those significant biological processes, most of them in metabolism. Four of these were shared AR and HIF1 targets, including genes encoding the regulatory glycolytic proteins HK2, PFKFB3, and SLC2A1. Most of the downregulated HIF1 targets were induced by hypoxia in androgen-responsive prostate cancer cell lines, confirming their role as hypoxia-responsive HIF1 targets in prostate cancer. Downregulation of HIF1 targets was consistent with the absence of HIF1α protein in xenografts and downregulation in patients by ADT (P<.001). Conclusions: AR repression by ADT may lead to downregulation of HIF1 signaling independently of hypoxic fraction, and this may contribute to

  5. Nerve growth factor in bladder dysfunction: contributing factor, biomarker, and therapeutic target

    NARCIS (Netherlands)

    Ochodnický, Peter; Cruz, Célia D.; Yoshimura, Naoki; Michel, Martin C.

    2011-01-01

    In the last two decades, nerve growth factor (NGF), initially described as a prototypical trophic factor in the development of sensory and sympathetic innervation, has emerged as a complex regulator of neural plasticity along the micturition pathways. This review aims to summarize the current

  6. Tritium inventory of a target factor in an ICF power plant

    International Nuclear Information System (INIS)

    Sherohman, J.W.

    1981-01-01

    A preliminary parametric study has been performed to estimate the tritium inventory of a conjectured Target Factory. The inventory of a proposed tritiated fuel processing system was determined as a function of production efficiency, storage factor, and time interval for the slowest processing step. Results indicated that a study of this type will be beneficial in evaluating possible processing schemes for the production of tritiated laser fusion targets

  7. Identification of direct targets of plant transcription factors using the GR fusion technique.

    Science.gov (United States)

    Yamaguchi, Nobutoshi; Winter, Cara M; Wellmer, Frank; Wagner, Doris

    2015-01-01

    The glucocorticoid receptor-dependent activation of plant transcription factors has proven to be a powerful tool for the identification of their direct target genes. In the absence of the synthetic steroid hormone dexamethasone (dex), transcription factors fused to the hormone-binding domain of the glucocorticoid receptor (TF-GR) are held in an inactive state, due to their cytoplasmic localization. This requires physical interaction with the heat shock protein 90 (HSP90) complex. Hormone binding leads to disruption of the interaction between GR and HSP90 and allows TF-GR fusion proteins to enter the nucleus. Once inside the nucleus, they bind to specific DNA sequences and immediately activate or repress expression of their targets. This system is well suited for the identification of direct target genes of transcription factors in plants, as (A) there is little basal protein activity in the absence of dex, (B) steroid application leads to rapid transcription factor activation, (C) no side effects of dex treatment are observed on the physiology of the plant, and (D) secondary effects of transcription factor activity can be eliminated by simultaneous application of an inhibitor of protein biosynthesis, cycloheximide (cyc). In this chapter, we describe detailed protocols for the preparation of plant material, for dex and cyc treatment, for RNA extraction, and for the PCR-based or genome-wide identification of direct targets of transcription factors fused to GR.

  8. Adaptive detection method of infrared small target based on target-background separation via robust principal component analysis

    Science.gov (United States)

    Wang, Chuanyun; Qin, Shiyin

    2015-03-01

    Motivated by the robust principal component analysis, infrared small target image is regarded as low-rank background matrix corrupted by sparse target and noise matrices, thus a new target-background separation model is designed, subsequently, an adaptive detection method of infrared small target is presented. Firstly, multi-scale transform and patch transform are used to generate an image patch set for infrared small target detection; secondly, target-background separation of each patch is achieved by recovering the low-rank and sparse matrices using adaptive weighting parameter; thirdly, the image reconstruction and fusion are carried out to obtain the entire separated background and target images; finally, the infrared small target detection is realized by threshold segmentation of template matching similarity measurement. In order to validate the performance of the proposed method, three experiments: target-background separation, background clutter suppression and infrared small target detection, are performed over different clutter background with real infrared small targets in single-frame or sequence images. A series of experiment results demonstrate that the proposed method can not only suppress background clutter effectively even if with strong noise interference but also detect targets accurately with low false alarm rate.

  9. TAL effectors: highly adaptable phytobacterial virulence factors and readily engineered DNA targeting proteins

    Science.gov (United States)

    Doyle, Erin L.; Stoddard, Barry L.; Voytas, Daniel F.; Bogdanove, Adam J.

    2013-01-01

    Transcription activator-like (TAL) effectors are transcription factors injected into plant cells by pathogenic bacteria in the genus Xanthomonas. They function as virulence factors by activating host genes important for disease, or as avirulence factors by turning on genes that provide resistance. DNA binding specificity is encoded by polymorphic repeats in each protein that correspond one-to-one with different nucleotides. This code has facilitated target identification and opened new avenues for engineering disease resistance. It has also enabled TAL effector customization for targeted gene control, genome editing, and other applications. This article reviews the structural basis for TAL effector-DNA specificity, the impact of the TAL effector-DNA code on plant pathology and engineered resistance, and recent accomplishments and future challenges in TAL effector-based DNA targeting. PMID:23707478

  10. More on EM for ML Factor Analysis.

    Science.gov (United States)

    Rubin, Donald B.; Thayer, Dorothy T.

    1983-01-01

    The authors respond to a criticism of their earlier article concerning the use of the EM algorithm in maximum likelihood factor analysis. Also included are the comments made by the reviewers of this article. (JKS)

  11. Decision factors for cooperative multiple warhead UAV target classification and attack with control applications

    Science.gov (United States)

    Decker, Douglas Dwayne

    Autonomous wide area search, classification and attack using Unmanned Combat Air Vehicles (UCAVs) is considered. The wide area search and attack scenario is modelled, capturing the important problem parameters of target density in the battle space, the density of false targets, the seeker and Autonomous Target Recognition (ATR) modules' performance parameters, as well as munition parameters such as search rate, time, and warhead lethality. The analysis in this research is an important stepping stone towards establishing benefits of cooperative search and engagement in a multi-vehicle scenario. This research uses probabilistic analysis to formulate and analytically solve for the probability of success in search and engagement as well as probabilities of other events of interest. Two methods are used to compute these probabilities. The first method utilizes a detailed examination of the sub-events required for the event of interest to occur. The second method utilizes a Markov chain approach. In each method, general expressions are first obtained that are applicable to any assumed a priori distributions of targets and false targets. These expressions are subsequently applied to a multiple warhead munition/UCAV operating in a single target/multiple false target scenario and then several multiple target/multiple false target scenarios. This research shows how the analytically derived results can be applied to all facets of the balanced system design and operation of Wide Area Search Munitions (WASM) including the evaluation of cooperation schemes and rules of engagement. This dissertation also formulates the problem as a control problem and examines the possibility of utilizing this formulation in the real-time estimation of the target and false target distribution parameters.

  12. Global analysis of small molecule binding to related protein targets.

    Directory of Open Access Journals (Sweden)

    Felix A Kruger

    2012-01-01

    Full Text Available We report on the integration of pharmacological data and homology information for a large scale analysis of small molecule binding to related targets. Differences in small molecule binding have been assessed for curated pairs of human to rat orthologs and also for recently diverged human paralogs. Our analysis shows that in general, small molecule binding is conserved for pairs of human to rat orthologs. Using statistical tests, we identified a small number of cases where small molecule binding is different between human and rat, some of which had previously been reported in the literature. Knowledge of species specific pharmacology can be advantageous for drug discovery, where rats are frequently used as a model system. For human paralogs, we demonstrate a global correlation between sequence identity and the binding of small molecules with equivalent affinity. Our findings provide an initial general model relating small molecule binding and sequence divergence, containing the foundations for a general model to anticipate and predict within-target-family selectivity.

  13. Potential Vaccine Targets against Rabbit Coccidiosis by Immunoproteomic Analysis.

    Science.gov (United States)

    Song, Hongyan; Dong, Ronglian; Qiu, Baofeng; Jing, Jin; Zhu, Shunxing; Liu, Chun; Jiang, Yingmei; Wu, Liucheng; Wang, Shengcun; Miao, Jin; Shao, Yixiang

    2017-02-01

    The aim of this study was to identify antigens for a vaccine or drug target to control rabbit coccidiosis. A combination of 2-dimensional electrophoresis, immunoblotting, and mass spectrometric analysis were used to identify novel antigens from the sporozoites of Eimeria stiedae . Protein spots were recognized by the sera of New Zealand rabbits infected artificially with E. stiedae . The proteins were characterized by matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF/TOF-MS) analysis in combination with bioinformatics. Approximately 868 protein spots were detected by silver-staining, and a total of 41 immunoreactive protein spots were recognized by anti- E. stiedae sera. Finally, 23 protein spots were successfully identified. The proteins such as heat shock protein 70 and aspartyl protease may have potential as immunodiagnostic or vaccine antigens. The immunoreactive proteins were found to possess a wide range of biological functions. This study is the first to report the proteins recognized by sera of infected rabbits with E. stiedae , which might be helpful in identifying potential targets for vaccine development to control rabbit coccidiosis.

  14. Analysis of technological, institutional and socioeconomic factors ...

    African Journals Online (AJOL)

    Analysis of technological, institutional and socioeconomic factors that influences poor reading culture among secondary school students in Nigeria. ... Proliferation and availability of smart phones, chatting culture and social media were identified as technological factors influencing poor reading culture among secondary ...

  15. The likelihood of achieving quantified road safety targets: a binary logistic regression model for possible factors.

    Science.gov (United States)

    Sze, N N; Wong, S C; Lee, C Y

    2014-12-01

    In past several decades, many countries have set quantified road safety targets to motivate transport authorities to develop systematic road safety strategies and measures and facilitate the achievement of continuous road safety improvement. Studies have been conducted to evaluate the association between the setting of quantified road safety targets and road fatality reduction, in both the short and long run, by comparing road fatalities before and after the implementation of a quantified road safety target. However, not much work has been done to evaluate whether the quantified road safety targets are actually achieved. In this study, we used a binary logistic regression model to examine the factors - including vehicle ownership, fatality rate, and national income, in addition to level of ambition and duration of target - that contribute to a target's success. We analyzed 55 quantified road safety targets set by 29 countries from 1981 to 2009, and the results indicate that targets that are in progress and with lower level of ambitions had a higher likelihood of eventually being achieved. Moreover, possible interaction effects on the association between level of ambition and the likelihood of success are also revealed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Retinopathy risk factors in type II diabetic patients using factor analysis and discriminant analysis.

    Science.gov (United States)

    Tazhibi, Mahdi; Sarrafzade, Sheida; Amini, Masoud

    2014-01-01

    Diabetes is one of the most common chronic diseases in the world. Incidence and prevalence of diabetes are increasing in developing countries as well as in Iran. Retinopathy is the most common chronic disorder in diabetic patients. In this study, we used the information of diabetic patients' reports that refer to endocrine and metabolism research center of Isfahan University of Medical Sciences to determine diabetic retinopathy risk factors. We used factor analysis to extract retinopathy's factors. Factor analysis is using to analyze multivariate data, in which a large number of dependent variables summarize into the fewer independent factors. Factor analysis is applied, in both diabetic and nondiabetic patients, separately. To investigate the efficacy of factor analysis, we used discriminant analysis. We investigated 3535 diabetic patients whose prevalence of retinopathy was 53.4%. Six factors were extracted in each group (i.e. diabetic and nondiabetic groups). These six factors were explained 69.5% and 69.6% of total variance in diabetic and nondiabetic groups, respectively. Using original variables such as sex, weight, blood sugar control method, and some laboratory variables, the correct classification rate of discriminant analysis was identified as 67.4%. However, it decreased to 49.5% by using extracted factors. Retinopathy is one of the important disorders in diabetic patients that involves a large number of variables and can affect its incidence. By the method of factor analysis, we summarize diabetic retinopathy risk factors. Factor analysis is applied separately, in two diabetic and nondiabetic group. In this way, 10 variables were summarized into the six factors. Discriminant analysis was used to investigate the efficacy of factor analysis. Although factor analysis is a powerful way to reduce the number of variables, in this study did not worked very well.

  17. Estimation of Partial Safety Factors and Target Failure Probability Based on Cost Optimization of Rubble Mound Breakwaters

    DEFF Research Database (Denmark)

    Kim, Seung-Woo; Suh, Kyung-Duck; Burcharth, Hans F.

    2010-01-01

    The breakwaters are designed by considering the cost optimization because a human risk is seldom considered. Most breakwaters, however, were constructed without considering the cost optimization. In this study, the optimum return period, target failure probability and the partial safety factors...... were evaluated by applying the cost optimization to the rubble mound breakwaters in Korea. The applied method was developed by Hans F. Burcharth and John D. Sorensen in relation to the PIANC Working Group 47. The optimum return period was determined as 50 years in many cases and was found as 100 years...... in the case of high real interest rate. Target failure probability was suggested by using the probabilities of failure corresponding to the optimum return period and those of reliability analysis of existing structures. The final target failure probability is about 60% for the initial limit state...

  18. Novel Data Fusion Method and Exploration of Multiple Information Sources for Transcription Factor Target Gene Prediction

    Science.gov (United States)

    Dai, Xiaofeng; Yli-Harja, Olli; Lähdesmäki, Harri

    2010-12-01

    Background. Revealing protein-DNA interactions is a key problem in understanding transcriptional regulation at mechanistic level. Computational methods have an important role in predicting transcription factor target gene genomewide. Multiple data fusion provides a natural way to improve transcription factor target gene predictions because sequence specificities alone are not sufficient to accurately predict transcription factor binding sites. Methods. Here we develop a new data fusion method to combine multiple genome-level data sources and study the extent to which DNA duplex stability and nucleosome positioning information, either alone or in combination with other data sources, can improve the prediction of transcription factor target gene. Results. Results on a carefully constructed test set of verified binding sites in mouse genome demonstrate that our new multiple data fusion method can reduce false positive rates, and that DNA duplex stability and nucleosome occupation data can improve the accuracy of transcription factor target gene predictions, especially when combined with other genome-level data sources. Cross-validation and other randomization tests confirm the predictive performance of our method. Our results also show that nonredundant data sources provide the most efficient data fusion.

  19. Nutritional status in the era of target therapy: poor nutrition is a prognostic factor in non-small cell lung cancer with activating epidermal growth factor receptor mutations.

    Science.gov (United States)

    Park, Sehhoon; Park, Seongyeol; Lee, Se-Hoon; Suh, Beomseok; Keam, Bhumsuk; Kim, Tae Min; Kim, Dong-Wan; Kim, Young Whan; Heo, Dae Seog

    2016-11-01

    Pretreatment nutritional status is an important prognostic factor in patients treated with conventional cytotoxic chemotherapy. In the era of target therapies, its value is overlooked and has not been investigated. The aim of our study is to evaluate the value of nutritional status in targeted therapy. A total of 2012 patients with non-small cell lung cancer (NSCLC) were reviewed and 630 patients with activating epidermal growth factor receptor (EGFR) mutation treated with EGFR tyrosine kinase inhibitor (TKI) were enrolled for the final analysis. Anemia, body mass index (BMI), and prognostic nutritional index (PNI) were considered as nutritional factors. Hazard ratio (HR), progression-free survival (PFS) and overall survival (OS) for each group were calculated by Cox proportional analysis. In addition, scores were applied for each category and the sum of scores was used for survival analysis. In univariable analysis, anemia (HR, 1.29; p = 0.015), BMI lower than 18.5 (HR, 1.98; p = 0.002), and PNI lower than 45 (HR, 1.57; p nutritional status is a prognostic marker in NSCLC patients treated with EGFR TKI. Hence, baseline nutritional status should be more carefully evaluated and adequate nutrition should be supplied to these patients.

  20. Cohort Analysis of a 24-Week Randomized Controlled Trial to Assess the Efficacy of a Novel, Partial Meal Replacement Program Targeting Weight Loss and Risk Factor Reduction in Overweight/Obese Adults.

    Science.gov (United States)

    Brindal, Emily; Hendrie, Gilly A; Taylor, Pennie; Freyne, Jill; Noakes, Manny

    2016-05-04

    Our aim was to design and evaluate a weight-loss program, including a partial meal replacement program, point-of-care testing and face-to-face and smartphone app support, appropriate for delivery in a community pharmacy setting. Overweight or obese adults (n = 146, 71.2% female, 48.18 ± 11.75 years old) were recruited to participate in a 24-week weight loss study and randomised to two app conditions. The dietary intervention was consistent regardless of app. Twelve weeks of clinic appointments with a trained consultant were followed by only app support for an additional 12 weeks. By week 24, retention was 57.5%. There were no differences between app conditions. Based on a cohort analysis of the trial, the mean decrease in weight from baseline to week 24 was 6.43 ± 1.06 kg for males (p < 0.001) and 5.66 ± 0.70 kg for females (p < 0.001). Mixed models also revealed decreases for LDL Cholesterol (-0.13 ± 0.08 mmol/L, nonsignificant), triglycerides (-0.08 ± 0.05 mmol/L, nonsignificant) and an increase in HDL cholesterol (+0.08 ± 0.04 mmol/L, ns) were not significant by week 24. Blood glucose (-0.23 ± 0.08 mmol/L, p = 0.040) and blood pressure (Systolic blood pressure -5.77 ± 1.21 Hg/mm, p < 0.001) were significantly lower at week 24 compared to baseline. Weight loss self-efficacy increased and remained significantly higher than baseline at week 24 (16.85 ± 2.93, p < 0.001). Overall, the program supported participants and was successful in achieving significant weight loss and improvements in health outcomes over 24 weeks.

  1. Cohort Analysis of a 24-Week Randomized Controlled Trial to Assess the Efficacy of a Novel, Partial Meal Replacement Program Targeting Weight Loss and Risk Factor Reduction in Overweight/Obese Adults

    Directory of Open Access Journals (Sweden)

    Emily Brindal

    2016-05-01

    Full Text Available Our aim was to design and evaluate a weight-loss program, including a partial meal replacement program, point-of-care testing and face-to-face and smartphone app support, appropriate for delivery in a community pharmacy setting. Overweight or obese adults (n = 146, 71.2% female, 48.18 ± 11.75 years old were recruited to participate in a 24-week weight loss study and randomised to two app conditions. The dietary intervention was consistent regardless of app. Twelve weeks of clinic appointments with a trained consultant were followed by only app support for an additional 12 weeks. By week 24, retention was 57.5%. There were no differences between app conditions. Based on a cohort analysis of the trial, the mean decrease in weight from baseline to week 24 was 6.43 ± 1.06 kg for males (p < 0.001 and 5.66 ± 0.70 kg for females (p < 0.001. Mixed models also revealed decreases for LDL Cholesterol (−0.13 ± 0.08 mmol/L, nonsignificant, triglycerides (−0.08 ± 0.05 mmol/L, nonsignificant and an increase in HDL cholesterol (+0.08 ± 0.04 mmol/L, ns were not significant by week 24. Blood glucose (−0.23 ± 0.08 mmol/L, p = 0.040 and blood pressure (Systolic blood pressure −5.77 ± 1.21 Hg/mm, p < 0.001 were significantly lower at week 24 compared to baseline. Weight loss self-efficacy increased and remained significantly higher than baseline at week 24 (16.85 ± 2.93, p < 0.001. Overall, the program supported participants and was successful in achieving significant weight loss and improvements in health outcomes over 24 weeks.

  2. Extending in silico mechanism-of-action analysis by annotating targets with pathways: application to cellular cytotoxicity readouts.

    Science.gov (United States)

    Liggi, Sonia; Drakakis, Georgios; Koutsoukas, Alexios; Cortes-Ciriano, Isidro; Martínez-Alonso, Patricia; Malliavin, Thérèse E; Velazquez-Campoy, Adrian; Brewerton, Suzanne C; Bodkin, Michael J; Evans, David A; Glen, Robert C; Carrodeguas, José Alberto; Bender, Andreas

    2014-01-01

    An in silico mechanism-of-action analysis protocol was developed, comprising molecule bioactivity profiling, annotation of predicted targets with pathways and calculation of enrichment factors to highlight targets and pathways more likely to be implicated in the studied phenotype. The method was applied to a cytotoxicity phenotypic endpoint, with enriched targets/pathways found to be statistically significant when compared with 100 random datasets. Application on a smaller apoptotic set (10 molecules) did not allowed to obtain statistically relevant results, suggesting that the protocol requires modification such as analysis of the most frequently predicted targets/annotated pathways. Pathway annotations improved the mechanism-of-action information gained by target prediction alone, allowing a better interpretation of the predictions and providing better mapping of targets onto pathways.

  3. Integrating human factors into process hazard analysis

    International Nuclear Information System (INIS)

    Kariuki, S.G.; Loewe, K.

    2007-01-01

    A comprehensive process hazard analysis (PHA) needs to address human factors. This paper describes an approach that systematically identifies human error in process design and the human factors that influence its production and propagation. It is deductive in nature and therefore considers human error as a top event. The combinations of different factors that may lead to this top event are analysed. It is qualitative in nature and is used in combination with other PHA methods. The method has an advantage because it does not look at the operator error as the sole contributor to the human failure within a system but a combination of all underlying factors

  4. Tumor necrosis factor alpha converting enzyme: an encouraging target for various inflammatory disorders.

    Science.gov (United States)

    Bahia, Malkeet S; Silakari, Om

    2010-05-01

    Tumor necrosis factor alpha is one of the most common pro-inflammatory cytokines responsible for various inflammatory disorders. It plays an important role in the origin and progression of rheumatoid arthritis and also in other autoimmune disease conditions. Some anti-tumor necrosis factor alpha antibodies like Enbrel, Humira and Remicade have been successfully used in these disease conditions as antagonists of tumor necrosis factor alpha. Inhibition of generation of active form of tumor necrosis factor alpha is a promising therapy for various inflammatory disorders. Therefore, the inhibition of an enzyme (tumor necrosis factor alpha converting enzyme), which is responsible for processing inactive form of tumor necrosis factor alpha into its active soluble form, is an encouraging target. Many tumor necrosis factor alpha converting enzyme inhibitors have been the candidates of clinical trials but none of them have reached in to the market because of their broad spectrum inhibitory activity for other matrix metalloproteases. Selectivity of tumor necrosis factor alpha converting enzyme inhibition over matrix metalloproteases is of utmost importance. If selectivity is achieved successfully, side-effects can be over-ruled and this approach may become a novel therapy for treatment of rheumatoid arthritis and other inflammatory disorders. This cytokine not only plays a pivotal role in inflammatory conditions but also in some cancerous conditions. Thus, successful targeting of tumor necrosis factor alpha converting enzyme may result in multifunctional therapy.

  5. Targeted DNA methylation analysis by next-generation sequencing.

    Science.gov (United States)

    Masser, Dustin R; Stanford, David R; Freeman, Willard M

    2015-02-24

    The role of epigenetic processes in the control of gene expression has been known for a number of years. DNA methylation at cytosine residues is of particular interest for epigenetic studies as it has been demonstrated to be both a long lasting and a dynamic regulator of gene expression. Efforts to examine epigenetic changes in health and disease have been hindered by the lack of high-throughput, quantitatively accurate methods. With the advent and popularization of next-generation sequencing (NGS) technologies, these tools are now being applied to epigenomics in addition to existing genomic and transcriptomic methodologies. For epigenetic investigations of cytosine methylation where regions of interest, such as specific gene promoters or CpG islands, have been identified and there is a need to examine significant numbers of samples with high quantitative accuracy, we have developed a method called Bisulfite Amplicon Sequencing (BSAS). This method combines bisulfite conversion with targeted amplification of regions of interest, transposome-mediated library construction and benchtop NGS. BSAS offers a rapid and efficient method for analysis of up to 10 kb of targeted regions in up to 96 samples at a time that can be performed by most research groups with basic molecular biology skills. The results provide absolute quantitation of cytosine methylation with base specificity. BSAS can be applied to any genomic region from any DNA source. This method is useful for hypothesis testing studies of target regions of interest as well as confirmation of regions identified in genome-wide methylation analyses such as whole genome bisulfite sequencing, reduced representation bisulfite sequencing, and methylated DNA immunoprecipitation sequencing.

  6. Challenges in thermal and hydraulic analysis of ADS target systems

    International Nuclear Information System (INIS)

    Groetzbach, G.; Batta, A.; Lefhalm, C.-H.; Otic, I.

    2004-01-01

    The liquid metal cooled spallation targets of Accelerator Driven nuclear reactor Systems obey high thermal loads; in addition some flow and cooling conditions are of a prototypical character; in contrast the operating conditions for the engaged materials are narrow; thus, the target development requires a very careful analysis by experimental and numerical means. Especially the cooling of the steel window, which is heated by the proton beam, needs special care. Some of the main goals of the experimental and numerical analyses of the thermal dynamics of those systems are discusses. The prediction of locally detached flows and of flows with larger recirculation areas suffers from insufficient turbulence modeling; this has to be compensated by using prototypical model experiments, e.g. with water, to select the adequate models and numerical schemes. The well known problems with the Reynolds analogy in predicting the heat transfer in liquid metals requires always prototypic liquid metal experiments to select and adapt the turbulent heat flux models. The uncertainties in liquid metal experiments cannot be neglected; so it is necessary to perform CFD calculations and experiments always hand in hand and to develop improve turbulent heat flux models. One contribution to an improved 3 or 4-equation model is deduced from recent Direct Numerical Simulation (DNS) data. (author)

  7. Activation analysis utilizing byproduct neutrons of cyclotron internal target runs

    International Nuclear Information System (INIS)

    Koh, K.; Finn, R.; Smith, P.; Tavano, E.; Dwyer, J.; Sheh, H.

    1985-01-01

    The neutron flux generated by the CS-30 cyclotron at Mt Sinai Medical Center during routine internal target runs was characterized by employing various elements as neutron monitors. The characteristic (p,xn) nuclear reactions from internal targets bombarded by 26.5 Mev protons and the cyclotron inner wall bombarded by stray protons produce a neutron flux of approximately 2 x 10 9 cm -2 s -1 at energies up to 22 MeV at a point immediately outside the cyclotron vacuum chamber. Samples exposed to neutron fluences up to 5 x 10 14 cm -2 were analyzed with a Ge(Li) detector. Although the detection limits are relatively high (i.e., Au-0.2 μg; In-1 μg; Na-50 μg), this mode of neutron activation analysis is ancillary to other irradiations and allows a large number of samples to be monitored. This approach may provide an alternative to a neutron generator for research activation applications. (orig.)

  8. SeedVicious: Analysis of microRNA target and near-target sites.

    Science.gov (United States)

    Marco, Antonio

    2018-01-01

    Here I describe seedVicious, a versatile microRNA target site prediction software that can be easily fitted into annotation pipelines and run over custom datasets. SeedVicious finds microRNA canonical sites plus other, less efficient, target sites. Among other novel features, seedVicious can compute evolutionary gains/losses of target sites using maximum parsimony, and also detect near-target sites, which have one nucleotide different from a canonical site. Near-target sites are important to study population variation in microRNA regulation. Some analyses suggest that near-target sites may also be functional sites, although there is no conclusive evidence for that, and they may actually be target alleles segregating in a population. SeedVicious does not aim to outperform but to complement existing microRNA prediction tools. For instance, the precision of TargetScan is almost doubled (from 11% to ~20%) when we filter predictions by the distance between target sites using this program. Interestingly, two adjacent canonical target sites are more likely to be present in bona fide target transcripts than pairs of target sites at slightly longer distances. The software is written in Perl and runs on 64-bit Unix computers (Linux and MacOS X). Users with no computing experience can also run the program in a dedicated web-server by uploading custom data, or browse pre-computed predictions. SeedVicious and its associated web-server and database (SeedBank) are distributed under the GPL/GNU license.

  9. Targeting the insulin-like growth factor network in cancer therapy.

    Science.gov (United States)

    Heidegger, Isabel; Pircher, Andreas; Klocker, Helmut; Massoner, Petra

    2011-04-15

    During the last decades, changes in the insulin-like growth factor (IGF) signaling have been related to the pathogenesis of cancer. Therefore, IGFs became highly attractive therapeutic cancer targets. Several drugs including monoclonal antibodies (mAB), small molecule tyrosine kinase inhibitors (RTKIs), anti-sense oligonucleotids (ASOs) and IGF-binding proteins (IGFBPs) targeting the IGF axis were developed. With over 60 ongoing clinical trials, the IGF1 receptor (IGF1R) is currently one of the most studied molecular targets in the field of oncology. In this review, we provide an overview on the IGF axis, its signaling pathways and its significance in neoplasia. We critically review the preclinical and clinical studies investigating the role of IGF1R as a cancer target and discuss preliminary results and possible limitations.

  10. An infrared small target detection method based on nonnegative matrix factorization and compressed sensing

    Science.gov (United States)

    Chen, Qiwei; Wang, Yiming

    2017-07-01

    According to the low rank property of the background and the sparse features of the target in infrared image, a novel infrared small target detection method based on the nonnegative matrix factorization (NMF) and compressed sensing technology was presented in this paper. This method trained background model through NMF, and then sampled the infrared image sequences directly using the block compressed sensing technology. Through the alternating direction method of multipliers (ADMM), the infrared small target was extracted and the background was recovered from the image. At the same time, the background was updated by the update algorithm, to adapt to the changes in the background. The simulation results show that the proposed method can detect the infrared target precisely and efficiently.

  11. ANALYSIS OF PULSE OPTICAL TARGET SEEKER STATIC CHARACTERISTICS AT TARGET AIRCRAFTS EXPOSURE

    Directory of Open Access Journals (Sweden)

    K. V. Trifonov,

    2016-01-01

    Full Text Available Subject of Research.The paper deals with operating principles of optical pulse target seekers based on quadrant photodiode when targets are located in short-range field region. Method. Target image shape and light intensity distribution can affect static characteristics and cause appearance of image energy maximums when targets are located in short-range field region. Physical modeling of static characteristics plotting process was carried out. The main idea of the proposed method lies in counting sums of image pixels intensities in every virtual area of the sensor while virtual frame of the whole photodetector is moving over the target image. Main Results. Most probable target illumination directions were analyzed. Critical distances when the first extra image energy maximum appears were calculated for every target illumination directions. Time of missile uncontrollable flight at a near miss distance was also estimated. Practical Relevance. Research results point out that using of control loop proper logic is required to provide reliable target shot down for active and semi-active laser homing systems. Also disabling of such systems should be carried out when targets are located in short-range field region.

  12. Imaging Diagnostic and Therapeutic Targets : Human Epidermal Growth Factor Receptor 2

    NARCIS (Netherlands)

    Gebhart, Geraldine; Flamen, Patrick; Vries, de Elisabeth G. E.; Jhaveri, Komal; Wimana, Zena

    2016-01-01

    Since the approval of trastuzumab, a humanized monoclonal antibody against the extracellular domain of human epidermal growth factor receptor 2 (HER2), 3 other HER2-targeting agents have gained regulatory approval: lapatinib, pertuzumab, and trastuzumab-emtansine. These agents have revolutionized

  13. Targeting Family Risk Factors in the Context of Treating Youth Depression: A Survey of Psychologists

    Science.gov (United States)

    Parra, Gilbert R.; Buckholdt, Kelly E.; Olsen, James P.; Jobe-Shields, Lisa; Davis, Genevieve L.; Gamble, Heather L.

    2011-01-01

    This study investigated the practices and perceptions of psychologists related to targeting family risk factors when treating youth depression. Participants were practicing psychologists recruited through the National Register of Health Service Providers in Psychology (N = 279). Psychologists completed a brief anonymous survey about addressing…

  14. A single gene target of an ETS-family transcription factor determines neuronal CO2-chemosensitivity

    DEFF Research Database (Denmark)

    Brandt, Julia P; Aziz-Zaman, Sonya; Juozaityte, Vaida

    2012-01-01

    . We report here a mechanism that endows C. elegans neurons with the ability to detect CO(2). The ETS-5 transcription factor is necessary for the specification of CO(2)-sensing BAG neurons. Expression of a single ETS-5 target gene, gcy-9, which encodes a receptor-type guanylate cyclase, is sufficient...

  15. Tumor infarction in mice by antibody-directed targeting of tissue factor to tumor vasculature

    NARCIS (Netherlands)

    Huang, XM; Molema, G; King, S; Watkins, L; Edgington, TS; Thorpe, PE

    1997-01-01

    Selective occlusion of tumor vasculature was tested as a therapy for solid tumors in a mouse model. The formation of blood clots (thrombosis) within the tumor Vessels was initiated by targeting the cell surface domain of human tissue factor, by means of a bispecific antibody, to an experimentally

  16. Targeting Host Factors to Treat West Nile and Dengue Viral Infections

    Directory of Open Access Journals (Sweden)

    Manoj N. Krishnan

    2014-02-01

    Full Text Available West Nile (WNV and Dengue (DENV viruses are major arboviral human pathogens belonging to the genus Flavivirus. At the current time, there are no approved prophylactics (e.g., vaccines or specific therapeutics available to prevent or treat human infections by these pathogens. Due to their minimal genome, these viruses require many host molecules for their replication and this offers a therapeutic avenue wherein host factors can be exploited as treatment targets. Since several host factors appear to be shared by many flaviviruses the strategy may result in pan-flaviviral inhibitors and may also attenuate the rapid emergence of drug resistant mutant viruses. The scope of this strategy is greatly enhanced by the recent en masse identification of host factors impacting on WNV and DENV infection. Excellent proof-of-principle experimental demonstrations for host-targeted control of infection and infection-induced pathogenesis have been reported for both WNV and DENV. These include exploiting not only those host factors supporting infection, but also targeting host processes contributing to pathogenesis and innate immune responses. While these early studies validated the host-targeting approach, extensive future investigations spanning a range of aspects are needed for a successful deployment in humans.

  17. Targeting host factors to treat West Nile and dengue viral infections.

    Science.gov (United States)

    Krishnan, Manoj N; Garcia-Blanco, Mariano A

    2014-02-10

    West Nile (WNV) and Dengue (DENV) viruses are major arboviral human pathogens belonging to the genus Flavivirus. At the current time, there are no approved prophylactics (e.g., vaccines) or specific therapeutics available to prevent or treat human infections by these pathogens. Due to their minimal genome, these viruses require many host molecules for their replication and this offers a therapeutic avenue wherein host factors can be exploited as treatment targets. Since several host factors appear to be shared by many flaviviruses the strategy may result in pan-flaviviral inhibitors and may also attenuate the rapid emergence of drug resistant mutant viruses. The scope of this strategy is greatly enhanced by the recent en masse identification of host factors impacting on WNV and DENV infection. Excellent proof-of-principle experimental demonstrations for host-targeted control of infection and infection-induced pathogenesis have been reported for both WNV and DENV. These include exploiting not only those host factors supporting infection, but also targeting host processes contributing to pathogenesis and innate immune responses. While these early studies validated the host-targeting approach, extensive future investigations spanning a range of aspects are needed for a successful deployment in humans.

  18. Targeting Villages for Rural Development Using Satellite Image Analysis.

    Science.gov (United States)

    Varshney, Kush R; Chen, George H; Abelson, Brian; Nowocin, Kendall; Sakhrani, Vivek; Xu, Ling; Spatocco, Brian L

    2015-03-01

    Satellite imagery is a form of big data that can be harnessed for many social good applications, especially those focusing on rural areas. In this article, we describe the common problem of selecting sites for and planning rural development activities as informed by remote sensing and satellite image analysis. Effective planning in poor rural areas benefits from information that is not available and is difficult to obtain at any appreciable scale by any means other than algorithms for estimation and inference from remotely sensed images. We discuss two cases in depth: the targeting of unconditional cash transfers to extremely poor villages in sub-Saharan Africa and the siting and planning of solar-powered microgrids in remote villages in India. From these cases, we draw out some common lessons broadly applicable to informed rural development.

  19. Audible sonar images generated with proprioception for target analysis.

    Science.gov (United States)

    Kuc, Roman B

    2017-05-01

    Some blind humans have demonstrated the ability to detect and classify objects with echolocation using palatal clicks. An audible-sonar robot mimics human click emissions, binaural hearing, and head movements to extract interaural time and level differences from target echoes. Targets of various complexity are examined by transverse displacements of the sonar and by target pose rotations that model movements performed by the blind. Controlled sonar movements executed by the robot provide data that model proprioception information available to blind humans for examining targets from various aspects. The audible sonar uses this sonar location and orientation information to form two-dimensional target images that are similar to medical diagnostic ultrasound tomograms. Simple targets, such as single round and square posts, produce distinguishable and recognizable images. More complex targets configured with several simple objects generate diffraction effects and multiple reflections that produce image artifacts. The presentation illustrates the capabilities and limitations of target classification from audible sonar images.

  20. National Climate Policies: Aiming at the Factor 4 Target by 2050?

    International Nuclear Information System (INIS)

    Godard, Olivier

    2016-01-01

    The paper considers how the governments of midsize developed countries could define national strategies to control greenhouse gas emissions, assuming that such strategies are the product of cognitive and ethical choices relating to global climate scenarios and the rule for allocating shares of expected global climate damage to individual States. After evaluating the carbon value linked to each cognitive-ethical configuration, I identify the configurations that justify the target of dividing national emissions by 4 between 1990 and 2050 - a goal known as 'Factor 4'. Lastly, I examine the resulting constraints on the shape of the control trajectory leading to that target

  1. Construction of a mouse model of factor VIII deficiency by gene targeting

    Energy Technology Data Exchange (ETDEWEB)

    Bi, L.; Lawler, A.; Gearhart, J. [Univ. of Pennsylvania School of Medicine, Philadelphia, PA (United States)] [and others

    1994-09-01

    To develop a small animal model of hemophilia A for gene therapy experiments, we set out to construct a mouse model for factor VIII deficiency by gene targeting. First, we screened a mouse liver cDNA library using a human FVIII cDNA probe. We cloned a 2.6 Kb partial mouse factor VIII cDNA which extends from 800 base pairs of the 3{prime} end of exon 14 to the 5{prime} end of exon 26. A mouse genomic library made from strain 129 was then screened to obtain genomic fragments covering the exons desired for homologous recombination. Two genomic clones were obtained, and one covering exon 15 through 22 was used for gene targeting. To make gene targeting constructs, a 5.8 Kb genomic DNA fragment covering exons 15 to 19 of the mouse FVIII gene was subcloned, and the neo expression cassette was inserted into exons 16 and 17 separately by different strategies. These two constructs were named MFVIIIC-16 and MFVIIIC-17. The constructs were linearized and transfected into strain 129 mouse ES cells by electroporation. Factor VIII gene-knockout ES cell lines were selected by G-418 and screened by genomic Southern blots. Eight exon 16 targeted cell lines and five exon 17 targeted cell lines were obtained. Three cell lines from each construct were injected into blastocysts and surgically transferred into foster mothers. Multiple chimeric mice with 70-90% hair color derived from the ES-cell genotype were seen with both constructs. Germ line transmission of the ES-cell genotype has been obtained for the MFVIIIC-16 construct, and multiple hemophilia A carrier females have been identified. Factor VIII-deficient males will be conceived soon.

  2. Fourier domain target transformation analysis in the thermal infrared

    Science.gov (United States)

    Anderson, D. L.

    1993-01-01

    Remote sensing uses of principal component analysis (PCA) of multispectral images include band selection and optimal color selection for display of information content. PCA has also been used for quantitative determination of mineral types and abundances given end member spectra. The preliminary results of the investigation of target transformation PCA (TTPCA) in the fourier domain to both identify end member spectra in an unknown spectrum, and to then calculate the relative concentrations of these selected end members are presented. Identification of endmember spectra in an unknown sample has previously been performed through bandmatching, expert systems, and binary classifiers. Both bandmatching and expert system techniques require the analyst to select bands or combinations of bands unique to each endmember. Thermal infrared mineral spectra have broad spectral features which vary subtly with composition. This makes identification of unique features difficult. Alternatively, whole spectra can be used in the classification process, in which case there is not need for an expert to identify unique spectra. Use of binary classifiers on whole spectra to identify endmember components has met with some success. These techniques can be used, along with a least squares fit approach on the endmembers identified, to derive compositional information. An alternative to the approach outlined above usese target transformation in conjunction with PCA to both identify and quantify the composition of unknown spectra. Preprocessing of the library and unknown spectra into the fourier domain, and using only a specific number of the components, allows for significant data volume reduction while maintaining a linear relationship in a Beer's Law sense. The approach taken here is to iteratively calculate concentrations, reducing the number of endmember components until only non-negative concentrations remain.

  3. Transcription profile of Escherichia coli: genomic SELEX search for regulatory targets of transcription factors

    Science.gov (United States)

    Ishihama, Akira; Shimada, Tomohiro; Yamazaki, Yukiko

    2016-01-01

    Bacterial genomes are transcribed by DNA-dependent RNA polymerase (RNAP), which achieves gene selectivity through interaction with sigma factors that recognize promoters, and transcription factors (TFs) that control the activity and specificity of RNAP holoenzyme. To understand the molecular mechanisms of transcriptional regulation, the identification of regulatory targets is needed for all these factors. We then performed genomic SELEX screenings of targets under the control of each sigma factor and each TF. Here we describe the assembly of 156 SELEX patterns of a total of 116 TFs performed in the presence and absence of effector ligands. The results reveal several novel concepts: (i) each TF regulates more targets than hitherto recognized; (ii) each promoter is regulated by more TFs than hitherto recognized; and (iii) the binding sites of some TFs are located within operons and even inside open reading frames. The binding sites of a set of global regulators, including cAMP receptor protein, LeuO and Lrp, overlap with those of the silencer H-NS, suggesting that certain global regulators play an anti-silencing role. To facilitate sharing of these accumulated SELEX datasets with the research community, we compiled a database, ‘Transcription Profile of Escherichia coli’ (www.shigen.nig.ac.jp/ecoli/tec/). PMID:26843427

  4. Leveraging growth factor induced macropinocytosis for targeted treatment of lung cancer.

    Science.gov (United States)

    Iglesias, Raul; Koria, Piyush

    2015-12-01

    Targeted therapy focused on highly expressed growth factor receptors is increasingly becoming popular for the treatment of lung cancer. Cancer cells exhibit higher levels of macropinocytosis than the normally quiescent non-cancerous cells, which can further be enhanced by growth factors. Here, we show the targeted enhancement of macropinocytosis in lung cancer cells for the delivery of the mitochondriotoxic peptide (KLAKLAK)2 using keratinocyte growth factor (KGF). We report the formation of a nanoparticle (NP) comprising of two chimeric fusion proteins, both fused to elastin-like polypeptide (ELP), (KLAKLAK)2-ELP and KGF-ELP. We show that (KLAKLAK)2-ELP nanoparticles are internalized via macropinocytosis and its internalization is facilitated by the interaction of the ELP domain with cell surface heparin sulfate proteoglycans. This internalization leads to mitochondrial depolarization and subsequent cell death. Also, we demonstrate that KGF-ELP selectively enhances macropinocytosis in cancer cells expressing high levels of the keratinocyte growth factor receptor (KGFR). Finally, the heterogeneous NPs consisting of (KLAKLAK)2-ELP and KGF-ELP selectively kill KGFR-expressing lung cancer cells. Hence, this multipronged approach of targeting highly active processes and receptors in cancer cells will be tremendously selective in the treatment of both early-stage and advanced-stage lung cancers, thereby improving patient's prognosis and survival rate.

  5. Transcription profile of Escherichia coli: genomic SELEX search for regulatory targets of transcription factors.

    Science.gov (United States)

    Ishihama, Akira; Shimada, Tomohiro; Yamazaki, Yukiko

    2016-03-18

    Bacterial genomes are transcribed by DNA-dependent RNA polymerase (RNAP), which achieves gene selectivity through interaction with sigma factors that recognize promoters, and transcription factors (TFs) that control the activity and specificity of RNAP holoenzyme. To understand the molecular mechanisms of transcriptional regulation, the identification of regulatory targets is needed for all these factors. We then performed genomic SELEX screenings of targets under the control of each sigma factor and each TF. Here we describe the assembly of 156 SELEX patterns of a total of 116 TFs performed in the presence and absence of effector ligands. The results reveal several novel concepts: (i) each TF regulates more targets than hitherto recognized; (ii) each promoter is regulated by more TFs than hitherto recognized; and (iii) the binding sites of some TFs are located within operons and even inside open reading frames. The binding sites of a set of global regulators, including cAMP receptor protein, LeuO and Lrp, overlap with those of the silencer H-NS, suggesting that certain global regulators play an anti-silencing role. To facilitate sharing of these accumulated SELEX datasets with the research community, we compiled a database, 'Transcription Profile of Escherichia coli' (www.shigen.nig.ac.jp/ecoli/tec/). © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  6. Global analysis of p53-regulated transcription identifies its direct targets and unexpected regulatory mechanisms.

    Science.gov (United States)

    Allen, Mary Ann; Andrysik, Zdenek; Dengler, Veronica L; Mellert, Hestia S; Guarnieri, Anna; Freeman, Justin A; Sullivan, Kelly D; Galbraith, Matthew D; Luo, Xin; Kraus, W Lee; Dowell, Robin D; Espinosa, Joaquin M

    2014-05-27

    The p53 transcription factor is a potent suppressor of tumor growth. We report here an analysis of its direct transcriptional program using Global Run-On sequencing (GRO-seq). Shortly after MDM2 inhibition by Nutlin-3, low levels of p53 rapidly activate ∼200 genes, most of them not previously established as direct targets. This immediate response involves all canonical p53 effector pathways, including apoptosis. Comparative global analysis of RNA synthesis vs steady state levels revealed that microarray profiling fails to identify low abundance transcripts directly activated by p53. Interestingly, p53 represses a subset of its activation targets before MDM2 inhibition. GRO-seq uncovered a plethora of gene-specific regulatory features affecting key survival and apoptotic genes within the p53 network. p53 regulates hundreds of enhancer-derived RNAs. Strikingly, direct p53 targets harbor pre-activated enhancers highly transcribed in p53 null cells. Altogether, these results enable the study of many uncharacterized p53 target genes and unexpected regulatory mechanisms.DOI: http://dx.doi.org/10.7554/eLife.02200.001. Copyright © 2014, Allen et al.

  7. Factor Economic Analysis at Forestry Enterprises

    Directory of Open Access Journals (Sweden)

    M.Yu. Chik

    2018-03-01

    Full Text Available The article studies the importance of economic analysis according to the results of research of scientific works of domestic and foreign scientists. The calculation of the influence of factors on the change in the cost of harvesting timber products by cost items has been performed. The results of the calculation of the influence of factors on the change of costs on 1 UAH are determined using the full cost of sold products. The variable and fixed costs and their distribution are allocated that influences the calculation of the impact of factors on cost changes on 1 UAH of sold products. The paper singles out the general results of calculating the influence of factors on cost changes on 1 UAH of sold products. According to the results of the analysis, the list of reserves for reducing the cost of production at forest enterprises was proposed. The main sources of reserves for reducing the prime cost of forest products at forest enterprises are investigated based on the conducted factor analysis.

  8. Cardio-oncology Related to Heart Failure: Epidermal Growth Factor Receptor Target-Based Therapy.

    Science.gov (United States)

    Kenigsberg, Benjamin; Jain, Varun; Barac, Ana

    2017-04-01

    Cancer therapy targeting the epidermal growth factor receptor (EGFR)/erythroblastic leukemia viral oncogene B (ErbB)/human EGFR receptor (HER) family of tyrosine kinases has been successfully used in treatment of several malignancies. The ErbB pathways play a role in the maintenance of cardiac homeostasis. This article summarizes current knowledge about EGFR/ErbB/HER receptor-targeted cancer therapeutics focusing on their cardiotoxicity profiles, molecular mechanisms, and implications in clinical cardio-oncology. The article discusses challenges in predicting, monitoring, and treating cardiac dysfunction and heart failure associated with ErbB-targeted cancer therapeutics and highlights opportunities for researchers and clinical investigators. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Capital Cost Optimization for Prefabrication: A Factor Analysis Evaluation Model

    Directory of Open Access Journals (Sweden)

    Hong Xue

    2018-01-01

    Full Text Available High capital cost is a significant hindrance to the promotion of prefabrication. In order to optimize cost management and reduce capital cost, this study aims to explore the latent factors and factor analysis evaluation model. Semi-structured interviews were conducted to explore potential variables and then questionnaire survey was employed to collect professionals’ views on their effects. After data collection, exploratory factor analysis was adopted to explore the latent factors. Seven latent factors were identified, including “Management Index”, “Construction Dissipation Index”, “Productivity Index”, “Design Efficiency Index”, “Transport Dissipation Index”, “Material increment Index” and “Depreciation amortization Index”. With these latent factors, a factor analysis evaluation model (FAEM, divided into factor analysis model (FAM and comprehensive evaluation model (CEM, was established. The FAM was used to explore the effect of observed variables on the high capital cost of prefabrication, while the CEM was used to evaluate comprehensive cost management level on prefabrication projects. Case studies were conducted to verify the models. The results revealed that collaborative management had a positive effect on capital cost of prefabrication. Material increment costs and labor costs had significant impacts on production cost. This study demonstrated the potential of on-site management and standardization design to reduce capital cost. Hence, collaborative management is necessary for cost management of prefabrication. Innovation and detailed design were needed to improve cost performance. The new form of precast component factories can be explored to reduce transportation cost. Meanwhile, targeted strategies can be adopted for different prefabrication projects. The findings optimized the capital cost and improved the cost performance through providing an evaluation and optimization model, which helps managers to

  10. What Is Rotating in Exploratory Factor Analysis?

    Science.gov (United States)

    Osborne, Jason W.

    2015-01-01

    Exploratory factor analysis (EFA) is one of the most commonly-reported quantitative methodology in the social sciences, yet much of the detail regarding what happens during an EFA remains unclear. The goal of this brief technical note is to explore what "rotation" is, what exactly is rotating, and why we use rotation when performing…

  11. An Adenovirus DNA Replication Factor, but Not Incoming Genome Complexes, Targets PML Nuclear Bodies.

    Science.gov (United States)

    Komatsu, Tetsuro; Nagata, Kyosuke; Wodrich, Harald

    2016-02-01

    Promyelocytic leukemia protein nuclear bodies (PML-NBs) are subnuclear domains implicated in cellular antiviral responses. Despite the antiviral activity, several nuclear replicating DNA viruses use the domains as deposition sites for the incoming viral genomes and/or as sites for viral DNA replication, suggesting that PML-NBs are functionally relevant during early viral infection to establish productive replication. Although PML-NBs and their components have also been implicated in the adenoviral life cycle, it remains unclear whether incoming adenoviral genome complexes target PML-NBs. Here we show using immunofluorescence and live-cell imaging analyses that incoming adenovirus genome complexes neither localize at nor recruit components of PML-NBs during early phases of infection. We further show that the viral DNA binding protein (DBP), an early expressed viral gene and essential DNA replication factor, independently targets PML-NBs. We show that DBP oligomerization is required to selectively recruit the PML-NB components Sp100 and USP7. Depletion experiments suggest that the absence of one PML-NB component might not affect the recruitment of other components toward DBP oligomers. Thus, our findings suggest a model in which an adenoviral DNA replication factor, but not incoming viral genome complexes, targets and modulates PML-NBs to support a conducive state for viral DNA replication and argue against a generalized concept that PML-NBs target incoming viral genomes. The immediate fate upon nuclear delivery of genomes of incoming DNA viruses is largely unclear. Early reports suggested that incoming genomes of herpesviruses are targeted and repressed by PML-NBs immediately upon nuclear import. Genome localization and/or viral DNA replication has also been observed at PML-NBs for other DNA viruses. Thus, it was suggested that PML-NBs may immediately sense and target nuclear viral genomes and hence serve as sites for deposition of incoming viral genomes and

  12. An SPSSR -Menu for Ordinal Factor Analysis

    Directory of Open Access Journals (Sweden)

    Mario Basto

    2012-01-01

    Full Text Available Exploratory factor analysis is a widely used statistical technique in the social sciences. It attempts to identify underlying factors that explain the pattern of correlations within a set of observed variables. A statistical software package is needed to perform the calculations. However, there are some limitations with popular statistical software packages, like SPSS. The R programming language is a free software package for statistical and graphical computing. It offers many packages written by contributors from all over the world and programming resources that allow it to overcome the dialog limitations of SPSS. This paper offers an SPSS dialog written in theR programming language with the help of some packages, so that researchers with little or no knowledge in programming, or those who are accustomed to making their calculations based on statistical dialogs, have more options when applying factor analysis to their data and hence can adopt a better approach when dealing with ordinal, Likert-type data.

  13. ANALYSIS OF THE FACTORS AFFECTING THE AVERAGE

    Directory of Open Access Journals (Sweden)

    Carmen BOGHEAN

    2013-12-01

    Full Text Available Productivity in agriculture most relevantly and concisely expresses the economic efficiency of using the factors of production. Labour productivity is affected by a considerable number of variables (including the relationship system and interdependence between factors, which differ in each economic sector and influence it, giving rise to a series of technical, economic and organizational idiosyncrasies. The purpose of this paper is to analyse the underlying factors of the average work productivity in agriculture, forestry and fishing. The analysis will take into account the data concerning the economically active population and the gross added value in agriculture, forestry and fishing in Romania during 2008-2011. The distribution of the average work productivity per factors affecting it is conducted by means of the u-substitution method.

  14. Radiological error: analysis, standard setting, targeted instruction and teamworking

    International Nuclear Information System (INIS)

    FitzGerald, Richard

    2005-01-01

    Diagnostic radiology does not have objective benchmarks for acceptable levels of missed diagnoses [1]. Until now, data collection of radiological discrepancies has been very time consuming. The culture within the specialty did not encourage it. However, public concern about patient safety is increasing. There have been recent innovations in compiling radiological interpretive discrepancy rates which may facilitate radiological standard setting. However standard setting alone will not optimise radiologists' performance or patient safety. We must use these new techniques in radiological discrepancy detection to stimulate greater knowledge sharing, targeted instruction and teamworking among radiologists. Not all radiological discrepancies are errors. Radiological discrepancy programmes must not be abused as an instrument for discrediting individual radiologists. Discrepancy rates must not be distorted as a weapon in turf battles. Radiological errors may be due to many causes and are often multifactorial. A systems approach to radiological error is required. Meaningful analysis of radiological discrepancies and errors is challenging. Valid standard setting will take time. Meanwhile, we need to develop top-up training, mentoring and rehabilitation programmes. (orig.)

  15. Functional transcription factor target discovery via compendia of binding and expression profiles.

    Science.gov (United States)

    Banks, Christopher J; Joshi, Anagha; Michoel, Tom

    2016-02-09

    Genome-wide experiments to map the DNA-binding locations of transcription-associated factors (TFs) have shown that the number of genes bound by a TF far exceeds the number of possible direct target genes. Distinguishing functional from non-functional binding is therefore a major challenge in the study of transcriptional regulation. We hypothesized that functional targets can be discovered by correlating binding and expression profiles across multiple experimental conditions. To test this hypothesis, we obtained ChIP-seq and RNA-seq data from matching cell types from the human ENCODE resource, considered promoter-proximal and distal cumulative regulatory models to map binding sites to genes, and used a combination of linear and non-linear measures to correlate binding and expression data. We found that a high degree of correlation between a gene's TF-binding and expression profiles was significantly more predictive of the gene being differentially expressed upon knockdown of that TF, compared to using binding sites in the cell type of interest only. Remarkably, TF targets predicted from correlation across a compendium of cell types were also predictive of functional targets in other cell types. Finally, correlation across a time course of ChIP-seq and RNA-seq experiments was also predictive of functional TF targets in that tissue.

  16. Influence of Cellular and Molecular Factors on Membrane Target Sensitivity to Insecticides.

    Science.gov (United States)

    Raymond, Valérie; Goven, Delphine; Benzidane, Yassine; List, Olivier; Lapied, Bruno

    2017-01-01

    The effective control of insect pests is based on the use of insecticides. Most of these compounds act on molecular targets in the insect nervous system. However, the largescale deployment of insecticide treatment has led to the development of resistance, which decreases insecticide efficacy. Although the resistance mechanisms are largely studied today, this review aims to point out new insights on the less-known cellular and molecular factors involved in the modulation of the sensitivity of the targets to insecticides. This review will focus on the phosphorylation/dephosphorylation process, the post-transcriptional events such as editing and alternative splicing and the influence of the association with auxiliary proteins of the receptors and/or ion channels targeted by insecticides. In addition, the involvement of calcium-dependent signaling pathways in the modulation of the sensitivity of the target to insecticides will also be considered and discussed. Finally, this review will insist on different strategies proposed to optimize the efficacy of insecticide treatment while reducing doses to decrease side effects on environment and on non-target organisms by combining two different chemical insecticides or a given active ingredient associated with biological and/or chemical synergistic agents. This review is part of the special issue "Insecticide Mode of Action: From Insect to Mammalian Toxicity". Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. Let-7 microRNAs Regenerate Peripheral Nerve Regeneration by Targeting Nerve Growth Factor

    OpenAIRE

    Li, Shiying; Wang, Xinghui; Gu, Yun; Chen, Chu; Wang, Yaxian; Liu, Jie; Hu, Wen; Yu, Bin; Wang, Yongjun; Ding, Fei; Liu, Yan; Gu, Xiaosong

    2015-01-01

    Peripheral nerve injury is a common clinical problem. Nerve growth factor (NGF) promotes peripheral nerve regeneration, but its clinical applications are limited by several constraints. In this study, we found that the time-dependent expression profiles of eight let-7 family members in the injured nerve after sciatic nerve injury were roughly similar to each other. Let-7 microRNAs (miRNAs) significantly reduced cell proliferation and migration of primary Schwann cells (SCs) by directly target...

  18. Nominal Performance Biosphere Dose Conversion Factor Analysis

    International Nuclear Information System (INIS)

    M. Wasiolek

    2004-01-01

    This analysis report is one of the technical reports containing documentation of the Environmental Radiation Model for Yucca Mountain, Nevada (ERMYN), a biosphere model supporting the Total System Performance Assessment (TSPA) for the license application (LA) for the Yucca Mountain repository. This analysis report describes the development of biosphere dose conversion factors (BDCFs) for the groundwater exposure scenario, and the development of conversion factors for assessing compliance with the groundwater protection standard. A graphical representation of the documentation hierarchy for the ERMYN is presented in Figure 1-1. This figure shows the interrelationships among the products (i.e., analysis and model reports) developed for biosphere modeling and provides an understanding of how this analysis report contributes to biosphere modeling. This report is one of two reports that develop biosphere BDCFs, which are input parameters for the TSPA-LA model. The ''Biosphere Model Report'' (BSC 2004 [DIRS 169460]) describes in detail the ERMYN conceptual model and mathematical model. The input parameter reports, shown to the right of the ''Biosphere Model Report'' in Figure 1-1, contain detailed description of the model input parameters, their development, and the relationship between the parameters and specific features events and processes (FEPs). This report describes biosphere model calculations and their output, the BDCFs, for the groundwater exposure scenario. The objectives of this analysis are to develop BDCFs for the groundwater exposure scenario for the three climate states considered in the TSPA-LA as well as conversion factors for evaluating compliance with the groundwater protection standard. The BDCFs will be used in performance assessment for calculating all-pathway annual doses for a given concentration of radionuclides in groundwater. The conversion factors will be used for calculating gross alpha particle activity in groundwater and the annual dose

  19. Limonene inhibits streptococcal biofilm formation by targeting surface-associated virulence factors.

    Science.gov (United States)

    Subramenium, Ganapathy Ashwinkumar; Vijayakumar, Karuppiah; Pandian, Shunmugiah Karutha

    2015-08-01

    The present study explores the efficacy of limonene, a cyclic terpene found in the rind of citrus fruits, for antibiofilm potential against species of the genus Streptococcus, which have been deeply studied worldwide owing to their multiple pathogenic efficacy. Limonene showed a concentration-dependent reduction in the biofilm formation of Streptococcus pyogenes (SF370), with minimal biofilm inhibitory concentration (MBIC) of 400 μg ml - 1. Limonene was found to possess about 75-95 % antibiofilm activity against all the pathogens tested, viz. Streptococcus pyogenes (SF370 and 5 clinical isolates), Streptococcus mutans (UA159) and Streptococcus mitis (ATCC 6249) at 400 μg ml - 1 concentration. Microscopic analysis of biofilm architecture revealed a quantitative breach in biofilm formation. Results of a surface-coating assay suggested that the possible mode of action of limonene could be by inhibiting bacterial adhesion to surfaces, thereby preventing the biofilm formation cascade. Susceptibility of limonene-treated Streptococcus pyogenes to healthy human blood goes in unison with gene expression studies in which the mga gene was found to be downregulated. Anti-cariogenic efficacy of limonene against Streptococcus mutans was confirmed, with inhibition of acid production and downregulation of the vicR gene. Downregulation of the covR, mga and vicR genes, which play a critical role in regulating surface-associated proteins in Streptococcus pyogenes and Streptococcus mutans, respectively, is yet further evidence to show that limonene targets surface-associated proteins. The results of physiological assays and gene expression studies clearly show that the surface-associated antagonistic mechanism of limonene also reduces surface-mediated virulence factors.

  20. Factor analysis for exercise stress radionuclide ventriculography

    International Nuclear Information System (INIS)

    Hirota, Kazuyoshi; Yasuda, Mitsutaka; Oku, Hisao; Ikuno, Yoshiyasu; Takeuchi, Kazuhide; Takeda, Tadanao; Ochi, Hironobu

    1987-01-01

    Using factor analysis, a new image processing in exercise stress radionuclide ventriculography, changes in factors associated with exercise were evaluated in 14 patients with angina pectoris or old myocardial infarction. The patients were imaged in the left anterior oblique projection, and three factor images were presented on a color coded scale. Abnormal factors (AF) were observed in 6 patients before exercise, 13 during exercise, and 4 after exercise. In 7 patients, the occurrence of AF was associated with exercise. Five of them became free from AF after exercise. Three patients showing AF before exercise had aggravation of AF during exercise. Overall, the occurrence or aggravation of AF was associated with exercise in ten (71 %) of the patients. The other three patients, however, had disappearance of AF during exercise. In the last patient, none of the AF was observed throughout the study. In view of a high incidence of AF associated with exercise, the factor analysis may have the potential in evaluating cardiac reverse from the viewpoint of left ventricular wall motion abnormality. (Namekawa, K.)

  1. Combined target and post-run target strategy for a comprehensive analysis of pesticides in ambient air using liquid chromatography-Orbitrap high resolution mass spectrometry.

    Science.gov (United States)

    Coscollà, Clara; León, Nuria; Pastor, Agustín; Yusà, Vicent

    2014-11-14

    A comprehensive strategy for the analysis of current airborne pesticides has been developed using liquid chromatography coupled to high resolution mass spectrometry. The methodology includes both quantitative target analysis and post-run target screening analysis. The quantitative method was validated after a previous statistical optimisation of the main factors governing the ion source ionization and a study of the single-stage Orbitrap fragmentation through the HCD cell. The quantitative method presented recoveries ranging from 73 to 116%, with precision (RSD) lower than 20%, for the 35 substances in the scope of the target method. The full-scan accurate mass data were acquired with a resolving power of 50000 FWHM (scan speed, 2 Hz), and alternating two acquisition events, ESI+ without fragmentation and ESI+ with fragmentation. The method-LOQ was 6.5 pg m(-3) for most of the target pesticides. For post-target screening a customized theoretical database, that included pesticides, metabolites and other substances such as emerging flame retardants was built up. For identification, accurate exact mass with less than 5 ppm, and some diagnostic ions including isotopes and/or fragments were used. The strategy was applied to ten samples collected in a rural area of Valencia (Spain). Four pesticides, namely carbendazim, metalaxyl, myclobutanil and terbuthylazine, were detected in concentrations from 16 pg m(-3) to 174 pg m(-3). Some pesticides and metabolites (endothal, fenfuram, terbuthylazine-2-OH), in addition to two flame retardants were tentatively identified in the post-run target screening analysis. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Next-to leading order analysis of target mass corrections to structure functions and asymmetries

    International Nuclear Information System (INIS)

    Brady, L.T.; Accardi, A.; Hobbs, T.J.; Melnitchouk, W.

    2011-01-01

    We perform a comprehensive analysis of target mass corrections (TMCs) to spin-averaged structure functions and asymmetries at next-to-leading order. Several different prescriptions for TMCs are considered, including the operator product expansion, and various approximations to it, collinear factorization, and xi-scaling. We assess the impact of each of these on a number of observables, such as the neutron to proton F 2 structure function ratio, and parity-violating electron scattering asymmetries for protons and deuterons which are sensitive to gamma-Z interference effects. The corrections from higher order radiative and nuclear effects on the parity-violating deuteron asymmetry are also quantified.

  3. Analysis of Features for Synthetic Aperture Radar Target Classification

    Science.gov (United States)

    2015-03-26

    Definition AFRL Air Force Research Laboratory ATR automatic target recognition CFAR constant false alarm rate CV civilian vehicles HOG histograms of oriented...percent bright constant false alarm rate ( CFAR ), and fractal dimension of the target in the image have been used and compared to training data to

  4. CRISPRTarget: bioinformatic prediction and analysis of crRNA targets

    NARCIS (Netherlands)

    Biswas, A.; Gagnon, J.N.; Brouns, S.J.J.; Fineran, P.C.; Brown, C.M.

    2013-01-01

    The bacterial and archaeal CRISPR/Cas adaptive immune system targets specific protospacer nucleotide sequences in invading organisms. This requires base pairing between processed CRISPR RNA and the target protospacer. For type I and II CRISPR/Cas systems, protospacer adjacent motifs (PAM) are

  5. Correction factor for hair analysis by PIXE

    International Nuclear Information System (INIS)

    Montenegro, E.C.; Baptista, G.B.; Castro Faria, L.V. de; Paschoa, A.S.

    1979-06-01

    The application of the Particle Induced X-ray Emission (PIXE) technique to analyse quantitatively the elemental composition of hair specimens brings about some difficulties in the interpretation of the data. The present paper proposes a correction factor to account for the effects of energy loss of the incident particle with penetration depth, and x-ray self-absorption when a particular geometrical distribution of elements in hair is assumed for calculational purposes. The correction factor has been applied to the analysis of hair contents Zn, Cu and Ca as a function of the energy of the incident particle.(Author) [pt

  6. Boolean Factor Analysis by Attractor Neural Network

    Czech Academy of Sciences Publication Activity Database

    Frolov, A. A.; Húsek, Dušan; Muraviev, I. P.; Polyakov, P.Y.

    2007-01-01

    Roč. 18, č. 3 (2007), s. 698-707 ISSN 1045-9227 R&D Projects: GA AV ČR 1ET100300419; GA ČR GA201/05/0079 Institutional research plan: CEZ:AV0Z10300504 Keywords : recurrent neural network * Hopfield-like neural network * associative memory * unsupervised learning * neural network architecture * neural network application * statistics * Boolean factor analysis * dimensionality reduction * features clustering * concepts search * information retrieval Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 2.769, year: 2007

  7. Nominal Performance Biosphere Dose Conversion Factor Analysis

    Energy Technology Data Exchange (ETDEWEB)

    M.A. Wasiolek

    2003-07-25

    This analysis report is one of the technical reports containing documentation of the Environmental Radiation Model for Yucca Mountain, Nevada (ERMYN), a biosphere model supporting the Total System Performance Assessment (TSPA) for the license application (LA) for the Yucca Mountain repository. This analysis report describes the development of biosphere dose conversion factors (BDCFs) for the groundwater exposure scenario, and the development of conversion factors for assessing compliance with the groundwater protection standard. A graphical representation of the documentation hierarchy for the ERMYN is presented in Figure 1-1. This figure shows the interrelationships among the products (i.e., analysis and model reports) developed for biosphere modeling and provides an understanding of how this analysis report contributes to biosphere modeling. This report is one of two reports that develop biosphere BDCFs, which are input parameters for the TSPA model. The ''Biosphere Model Report'' (BSC 2003 [DIRS 164186]) describes in detail the ERMYN conceptual model and mathematical model. The input parameter reports (BSC 2003 [DIRS 160964]; BSC 2003 [DIRS 160965]; BSC 2003 [DIRS 160976]; BSC 2003 [DIRS 161239]; BSC 2003 [DIRS 161241]) contain detailed description of the model input parameters. This report describes biosphere model calculations and their output, the BDCFs, for the groundwater exposure scenario. The objectives of this analysis are to develop BDCFs and conversion factors for the TSPA. The BDCFs will be used in performance assessment for calculating annual doses for a given concentration of radionuclides in groundwater. The conversion factors will be used for calculating gross alpha particle activity in groundwater and the annual dose from beta- and photon-emitting radionuclides.

  8. Nominal Performance Biosphere Dose Conversion Factor Analysis

    Energy Technology Data Exchange (ETDEWEB)

    M.A. Wasiolek

    2005-04-28

    This analysis report is one of the technical reports containing documentation of the Environmental Radiation Model for Yucca Mountain, Nevada (ERMYN), a biosphere model supporting the Total System Performance Assessment (TSPA) for the license application (LA) for the Yucca Mountain repository. This analysis report describes the development of biosphere dose conversion factors (BDCFs) for the groundwater exposure scenario, and the development of conversion factors for assessing compliance with the groundwater protection standards. A graphical representation of the documentation hierarchy for the ERMYN is presented in Figure 1-1. This figure shows the interrelationships among the products (i.e., analysis and model reports) developed for biosphere modeling and provides an understanding of how this analysis report contributes to biosphere modeling. This report is one of two reports that develop BDCFs, which are input parameters for the TSPA-LA model. The ''Biosphere Model Report'' (BSC 2004 [DIRS 169460]) describes in detail the ERMYN conceptual model and mathematical model. The input parameter reports, shown to the right of the ''Biosphere Model Report'' in Figure 1-1, contain detailed description of the model input parameters, their development, and the relationship between the parameters and specific features events and processes (FEPs). This report describes biosphere model calculations and their output, the BDCFs, for the groundwater exposure scenario. This analysis receives direct input from the outputs of the ''Biosphere Model Report'' (BSC 2004 [DIRS 169460]) and the five analyses that develop parameter values for the biosphere model (BSC 2005 [DIRS 172827]; BSC 2004 [DIRS 169672]; BSC 2004 [DIRS 169673]; BSC 2004 [DIRS 169458]; BSC 2004 [DIRS 169459]). The results of this report are further analyzed in the ''Biosphere Dose Conversion Factor Importance and Sensitivity Analysis

  9. Nominal Performance Biosphere Dose Conversion Factor Analysis

    International Nuclear Information System (INIS)

    M.A. Wasiolek

    2005-01-01

    This analysis report is one of the technical reports containing documentation of the Environmental Radiation Model for Yucca Mountain, Nevada (ERMYN), a biosphere model supporting the Total System Performance Assessment (TSPA) for the license application (LA) for the Yucca Mountain repository. This analysis report describes the development of biosphere dose conversion factors (BDCFs) for the groundwater exposure scenario, and the development of conversion factors for assessing compliance with the groundwater protection standards. A graphical representation of the documentation hierarchy for the ERMYN is presented in Figure 1-1. This figure shows the interrelationships among the products (i.e., analysis and model reports) developed for biosphere modeling and provides an understanding of how this analysis report contributes to biosphere modeling. This report is one of two reports that develop BDCFs, which are input parameters for the TSPA-LA model. The ''Biosphere Model Report'' (BSC 2004 [DIRS 169460]) describes in detail the ERMYN conceptual model and mathematical model. The input parameter reports, shown to the right of the ''Biosphere Model Report'' in Figure 1-1, contain detailed description of the model input parameters, their development, and the relationship between the parameters and specific features events and processes (FEPs). This report describes biosphere model calculations and their output, the BDCFs, for the groundwater exposure scenario. This analysis receives direct input from the outputs of the ''Biosphere Model Report'' (BSC 2004 [DIRS 169460]) and the five analyses that develop parameter values for the biosphere model (BSC 2005 [DIRS 172827]; BSC 2004 [DIRS 169672]; BSC 2004 [DIRS 169673]; BSC 2004 [DIRS 169458]; BSC 2004 [DIRS 169459]). The results of this report are further analyzed in the ''Biosphere Dose Conversion Factor Importance and Sensitivity Analysis'' (Figure 1-1). The objectives of this analysis are to develop BDCFs for the

  10. Scalable group level probabilistic sparse factor analysis

    DEFF Research Database (Denmark)

    Hinrich, Jesper Løve; Nielsen, Søren Føns Vind; Riis, Nicolai Andre Brogaard

    2017-01-01

    Many data-driven approaches exist to extract neural representations of functional magnetic resonance imaging (fMRI) data, but most of them lack a proper probabilistic formulation. We propose a scalable group level probabilistic sparse factor analysis (psFA) allowing spatially sparse maps, component...... pruning using automatic relevance determination (ARD) and subject specific heteroscedastic spatial noise modeling. For task-based and resting state fMRI, we show that the sparsity constraint gives rise to components similar to those obtained by group independent component analysis. The noise modeling...

  11. Research and Analysis Laser Target Optics Characteristics and Signal Recognition Processing in Detection Screen System

    Directory of Open Access Journals (Sweden)

    Hanshan LI

    2014-02-01

    Full Text Available In order to improve the measurement accuracy of the laser measurement distance system, this paper study the laser target optics characteristics based on the laser detection principle in the laser measurement distance system. A calculation model of laser reflective echo signal is put forward by analyzing the influence factors on the detector output value, and discuss the relationship between the distance from the detector to the target, the laser wavelength, the Transmission power of laser and the detector output power, the radiation intensity, and use the Fisher identification and modulus maxima method based on wavelet analysis to distinguish and identify the received echo signals. By the theoretical calculation and experimentation, the result shows the laser target optics characteristics are consistent with the calculation method of radiation. The real reflective signal can be identified by using wavelet transform, and the numerical value of the distance between the target and the detector is larger, the numerical value of echo signal will be smaller.

  12. Targeting gender: A content analysis of alcohol advertising in magazines.

    Science.gov (United States)

    Jung, A-Reum; Hovland, Roxanne

    2016-01-01

    Creating target specific advertising is fundamental to maximizing advertising effectiveness. When crafting an advertisement, message and creative strategies are considered important because they affect target audiences' attitudes toward advertised products. This study endeavored to find advertising strategies that are likely to have special appeal for men or women by examining alcohol advertising in magazines. The results show that the substance of the messages is the same for men and women, but they only differ in terms of presentation. However, regardless of gender group, the most commonly used strategies in alcohol advertising are appeals to the target audience's emotions.

  13. Identification of elongation factor G as the conserved cellular target of argyrin B.

    Directory of Open Access Journals (Sweden)

    Beat Nyfeler

    Full Text Available Argyrins, produced by myxobacteria and actinomycetes, are cyclic octapeptides with antibacterial and antitumor activity. Here, we identify elongation factor G (EF-G as the cellular target of argyrin B in bacteria, via resistant mutant selection and whole genome sequencing, biophysical binding studies and crystallography. Argyrin B binds a novel allosteric pocket in EF-G, distinct from the known EF-G inhibitor antibiotic fusidic acid, revealing a new mode of protein synthesis inhibition. In eukaryotic cells, argyrin B was found to target mitochondrial elongation factor G1 (EF-G1, the closest homologue of bacterial EF-G. By blocking mitochondrial translation, argyrin B depletes electron transport components and inhibits the growth of yeast and tumor cells. Further supporting direct inhibition of EF-G1, expression of an argyrin B-binding deficient EF-G1 L693Q variant partially rescued argyrin B-sensitivity in tumor cells. In summary, we show that argyrin B is an antibacterial and cytotoxic agent that inhibits the evolutionarily conserved target EF-G, blocking protein synthesis in bacteria and mitochondrial translation in yeast and mammalian cells.

  14. Performance Analysis on ISAR Imaging of Space Targets

    Directory of Open Access Journals (Sweden)

    Zhou Yejian

    2017-02-01

    Full Text Available Usually, in traditional Inverse Synthetic Aperture Radar (ISAR systems design and mode selection for space satellite targets, coherent integration gain in azimuth direction hardly can be analyzed, which depends on target’s motion. In this study, we combine the target orbit parameters to determine its motion relative to radar and deduce coherent integration equation in ISAR imaging to realize the selection of imaging intervals based on coherent integration, which can ensure the resolution in azimuth direction. Meanwhile, we analyze the influence of target orbit altitude to echo power and imaging Signal-to-Noise Ratio (SNR that provides a new indicator for space observation ISAR systems design. The result of simulation experiment illustrates that with target orbit altitude increasing, coherent integration gain in azimuth direction of large-angular observation offsets the decreasing of imaging SNR in a degree, which provides a brand-new perspective for space observation ISAR systems and signal processing design.

  15. DISRUPTIVE EVENT BIOSPHERE DOSE CONVERSION FACTOR ANALYSIS

    International Nuclear Information System (INIS)

    M.A. Wasiolek

    2005-01-01

    This analysis report is one of the technical reports containing documentation of the Environmental Radiation Model for Yucca Mountain, Nevada (ERMYN), a biosphere model supporting the total system performance assessment (TSPA) for the license application (LA) for the Yucca Mountain repository. This analysis report describes the development of biosphere dose conversion factors (BDCFs) for the volcanic ash exposure scenario, and the development of dose factors for calculating inhalation dose during volcanic eruption. A graphical representation of the documentation hierarchy for the ERMYN is presented in Figure 1-1. This figure shows the interrelationships among the products (i.e., analysis and model reports) developed for biosphere modeling and provides an understanding of how this analysis report contributes to biosphere modeling. This report is one of two reports that develop biosphere BDCFs, which are input parameters for the TSPA model. The Biosphere Model Report (BSC 2004 [DIRS 169460]) describes in detail the ERMYN conceptual model and mathematical model. The input parameter reports, shown to the right of the Biosphere Model Report in Figure 1-1, contain detailed descriptions of the model input parameters, their development and the relationship between the parameters and specific features, events and processes (FEPs). This report describes biosphere model calculations and their output, the BDCFs, for the volcanic ash exposure scenario. This analysis receives direct input from the outputs of the ''Biosphere Model Report'' (BSC 2004 [DIRS 169460]) and from the five analyses that develop parameter values for the biosphere model (BSC 2005 [DIRS 172827]; BSC 2004 [DIRS 169672]; BSC 2004 [DIRS 169673]; BSC 2004 [DIRS 169458]; and BSC 2004 [DIRS 169459]). The results of this report are further analyzed in the ''Biosphere Dose Conversion Factor Importance and Sensitivity Analysis'' (Figure 1-1). The objective of this analysis was to develop the BDCFs for the volcanic

  16. Integrated targeted and non-targeted analysis of water sample extracts with micro-scale UHPLC–MS

    Directory of Open Access Journals (Sweden)

    Dominik Deyerling

    2015-01-01

    • The filtering of database hits for two criteria (exact mass and partition coefficient significantly reduced the list of suspects and at the same time rendered it possible to perform non-target analysis with lower mass accuracy (no lock-spray in the range of 20–500 ppm.

  17. A Beginner’s Guide to Factor Analysis: Focusing on Exploratory Factor Analysis

    Directory of Open Access Journals (Sweden)

    An Gie Yong

    2013-10-01

    Full Text Available The following paper discusses exploratory factor analysis and gives an overview of the statistical technique and how it is used in various research designs and applications. A basic outline of how the technique works and its criteria, including its main assumptions are discussed as well as when it should be used. Mathematical theories are explored to enlighten students on how exploratory factor analysis works, an example of how to run an exploratory factor analysis on SPSS is given, and finally a section on how to write up the results is provided. This will allow readers to develop a better understanding of when to employ factor analysis and how to interpret the tables and graphs in the output.

  18. Clinical learning environment inventory: factor analysis.

    Science.gov (United States)

    Newton, Jennifer M; Jolly, Brian C; Ockerby, Cherene M; Cross, Wendy M

    2010-06-01

    This paper is a report of the psychometric testing of the Clinical Learning Environment Inventory. The clinical learning environment is a complex socio-cultural entity that offers a variety of opportunities to engage or disengage in learning. The Clinical Learning Environment Inventory is a self-report instrument consisting of 42 items classified into six scales: personalization, student involvement, task orientation, innovation, satisfaction and individualization. It was developed to examine undergraduate nursing students' perceptions of the learning environment whilst on placement in clinical settings. As a component of a longitudinal project, Bachelor of Nursing students (n = 659) from two campuses of a university in Australia, completed the Clinical Learning Environment Inventory from 2006 to 2008. Principal components analysis using varimax rotation was conducted to explore the factor structure of the inventory. Data for 513 students (77%) were eligible for inclusion. Constraining data to a 6-factor solution explained 51% of the variance. The factors identified were: student-centredness, affordances and engagement, individualization, fostering workplace learning, valuing nurses' work, and innovative and adaptive workplace culture. These factors were reviewed against recent theoretical developments in the literature. The study offers an empirically based and theoretically informed extension of the original Clinical Learning Environment Inventory, which had previously relied on ad hoc clustering of items and the use of internal reliability of its sub-scales. Further research is required to establish the consistency of these new factors.

  19. miR-218 suppresses cardiac myxoma proliferation by targeting myocyte enhancer factor 2D.

    Science.gov (United States)

    Cao, Quanxing; Dong, Pingshuan; Wang, Yanyu; Zhang, Junwei; Shi, Xinge; Wang, Yongsheng

    2015-05-01

    Cardiac myxoma is the most common type of human heart tumor, yet the molecular mechanism is still poorly understood. In the present study, we found that the level of myocyte enhancer factor 2D (MEF2D), a key regulatory protein for cardiac development, was elevated in specimens of cardiac myxoma, and was positively associated with the proliferation of myxoma cells. MEF2D suppression reduced the proliferation of myxoma cells and its tumorigenicity. Cell cycle progression was also inhibited by MEF2D suppression. miR-218, which is downregulated in myxoma, suppressed MEF2D expression by targeting its mRNA 3'UTR. Altogether, we found that miR-218/MEF2D may be an effective target for myxoma treatment.

  20. Nominal Performance Biosphere Dose Conversion Factor Analysis

    Energy Technology Data Exchange (ETDEWEB)

    M. Wasiolek

    2004-09-08

    This analysis report is one of the technical reports containing documentation of the Environmental Radiation Model for Yucca Mountain, Nevada (ERMYN), a biosphere model supporting the Total System Performance Assessment (TSPA) for the license application (LA) for the Yucca Mountain repository. This analysis report describes the development of biosphere dose conversion factors (BDCFs) for the groundwater exposure scenario, and the development of conversion factors for assessing compliance with the groundwater protection standard. A graphical representation of the documentation hierarchy for the ERMYN is presented in Figure 1-1. This figure shows the interrelationships among the products (i.e., analysis and model reports) developed for biosphere modeling and provides an understanding of how this analysis report contributes to biosphere modeling. This report is one of two reports that develop biosphere BDCFs, which are input parameters for the TSPA-LA model. The ''Biosphere Model Report'' (BSC 2004 [DIRS 169460]) describes in detail the ERMYN conceptual model and mathematical model. The input parameter reports, shown to the right of the ''Biosphere Model Report'' in Figure 1-1, contain detailed description of the model input parameters, their development, and the relationship between the parameters and specific features events and processes (FEPs). This report describes biosphere model calculations and their output, the BDCFs, for the groundwater exposure scenario. The objectives of this analysis are to develop BDCFs for the groundwater exposure scenario for the three climate states considered in the TSPA-LA as well as conversion factors for evaluating compliance with the groundwater protection standard. The BDCFs will be used in performance assessment for calculating all-pathway annual doses for a given concentration of radionuclides in groundwater. The conversion factors will be used for calculating gross alpha particle

  1. Exploratory factor analysis in Rehabilitation Psychology: a content analysis.

    Science.gov (United States)

    Roberson, Richard B; Elliott, Timothy R; Chang, Jessica E; Hill, Jessica N

    2014-11-01

    Our objective was to examine the use and quality of exploratory factor analysis (EFA) in articles published in Rehabilitation Psychology. Trained raters examined 66 separate exploratory factor analyses in 47 articles published between 1999 and April 2014. The raters recorded the aim of the EFAs, the distributional statistics, sample size, factor retention method(s), extraction and rotation method(s), and whether the pattern coefficients, structure coefficients, and the matrix of association were reported. The primary use of the EFAs was scale development, but the most widely used extraction and rotation method was principle component analysis, with varimax rotation. When determining how many factors to retain, multiple methods (e.g., scree plot, parallel analysis) were used most often. Many articles did not report enough information to allow for the duplication of their results. EFA relies on authors' choices (e.g., factor retention rules extraction, rotation methods), and few articles adhered to all of the best practices. The current findings are compared to other empirical investigations into the use of EFA in published research. Recommendations for improving EFA reporting practices in rehabilitation psychology research are provided.

  2. Disruptive Event Biosphere Dose Conversion Factor Analysis

    International Nuclear Information System (INIS)

    M. A. Wasiolek

    2003-01-01

    This analysis report, ''Disruptive Event Biosphere Dose Conversion Factor Analysis'', is one of the technical reports containing documentation of the ERMYN (Environmental Radiation Model for Yucca Mountain Nevada) biosphere model for the geologic repository at Yucca Mountain, its input parameters, and the application of the model to perform the dose assessment for the repository. The biosphere model is one of a series of process models supporting the Total System Performance Assessment (TSPA) for the Yucca Mountain repository. A graphical representation of the documentation hierarchy for the ERMYN is presented in Figure 1-1. This figure shows the interrelationships among the products (i.e., analysis and model reports) developed for biosphere modeling and provides an understanding of how this analysis report contributes to biosphere modeling. This report is one of the two reports that develop biosphere dose conversion factors (BDCFs), which are input parameters for the TSPA model. The ''Biosphere Model Report'' (BSC 2003 [DIRS 164186]) describes in detail the conceptual model as well as the mathematical model and lists its input parameters. Model input parameters are developed and described in detail in five analysis report (BSC 2003 [DIRS 160964], BSC 2003 [DIRS 160965], BSC 2003 [DIRS 160976], BSC 2003 [DIRS 161239], and BSC 2003 [DIRS 161241]). The objective of this analysis was to develop the BDCFs for the volcanic ash exposure scenario and the dose factors (DFs) for calculating inhalation doses during volcanic eruption (eruption phase of the volcanic event). The volcanic ash exposure scenario is hereafter referred to as the volcanic ash scenario. For the volcanic ash scenario, the mode of radionuclide release into the biosphere is a volcanic eruption through the repository with the resulting entrainment of contaminated waste in the tephra and the subsequent atmospheric transport and dispersion of contaminated material in the biosphere. The biosphere process

  3. Disruptive Event Biosphere Dose Conversion Factor Analysis

    Energy Technology Data Exchange (ETDEWEB)

    M. A. Wasiolek

    2003-07-21

    This analysis report, ''Disruptive Event Biosphere Dose Conversion Factor Analysis'', is one of the technical reports containing documentation of the ERMYN (Environmental Radiation Model for Yucca Mountain Nevada) biosphere model for the geologic repository at Yucca Mountain, its input parameters, and the application of the model to perform the dose assessment for the repository. The biosphere model is one of a series of process models supporting the Total System Performance Assessment (TSPA) for the Yucca Mountain repository. A graphical representation of the documentation hierarchy for the ERMYN is presented in Figure 1-1. This figure shows the interrelationships among the products (i.e., analysis and model reports) developed for biosphere modeling and provides an understanding of how this analysis report contributes to biosphere modeling. This report is one of the two reports that develop biosphere dose conversion factors (BDCFs), which are input parameters for the TSPA model. The ''Biosphere Model Report'' (BSC 2003 [DIRS 164186]) describes in detail the conceptual model as well as the mathematical model and lists its input parameters. Model input parameters are developed and described in detail in five analysis report (BSC 2003 [DIRS 160964], BSC 2003 [DIRS 160965], BSC 2003 [DIRS 160976], BSC 2003 [DIRS 161239], and BSC 2003 [DIRS 161241]). The objective of this analysis was to develop the BDCFs for the volcanic ash exposure scenario and the dose factors (DFs) for calculating inhalation doses during volcanic eruption (eruption phase of the volcanic event). The volcanic ash exposure scenario is hereafter referred to as the volcanic ash scenario. For the volcanic ash scenario, the mode of radionuclide release into the biosphere is a volcanic eruption through the repository with the resulting entrainment of contaminated waste in the tephra and the subsequent atmospheric transport and dispersion of contaminated material in

  4. Determining the Number of Factors in P-Technique Factor Analysis

    Science.gov (United States)

    Lo, Lawrence L.; Molenaar, Peter C. M.; Rovine, Michael

    2017-01-01

    Determining the number of factors is a critical first step in exploratory factor analysis. Although various criteria and methods for determining the number of factors have been evaluated in the usual between-subjects R-technique factor analysis, there is still question of how these methods perform in within-subjects P-technique factor analysis. A…

  5. Exploratory Bi-Factor Analysis: The Oblique Case

    Science.gov (United States)

    Jennrich, Robert I.; Bentler, Peter M.

    2012-01-01

    Bi-factor analysis is a form of confirmatory factor analysis originally introduced by Holzinger and Swineford ("Psychometrika" 47:41-54, 1937). The bi-factor model has a general factor, a number of group factors, and an explicit bi-factor structure. Jennrich and Bentler ("Psychometrika" 76:537-549, 2011) introduced an exploratory form of bi-factor…

  6. Defining the factors that contribute to on-target specificity of antisense oligonucleotides.

    Directory of Open Access Journals (Sweden)

    Walt F Lima

    Full Text Available To better understand the factors that influence the activity and specificity of antisense oligonucleotides (ASOs, we designed a minigene encoding superoxide dismutase 1 (SOD-1 and cloned the minigene into vectors for T7 transcription of pre-mRNA and splicing in a nuclear extract or for stable integration in cells. We designed a series of ASOs that covered the entire mRNA and determined the binding affinities and activities of the ASOs in a cell-free system and in cells. The mRNA bound known RNA-binding proteins on predicted binding sites in the mRNA. The higher order structure of the mRNA had a significantly greater effect than the RNA-binding proteins on ASO binding affinities as the ASO activities in cells and in the cell-free systems were consistent. We identified several ASOs that exhibited off-target hybridization to the SOD-1 minigene mRNA in the cell-free system. Off-target hybridization occurred only at highly accessible unstructured sites in the mRNA and these interactions were inhibited by both the higher order structure of the mRNA and by RNA-binding proteins. The same off-target hybridization interactions were identified in cells that overexpress E. coli RNase H1. No off-target activity was observed for cells expressing only endogenous human RNase H1. Neither were these off-target heteroduplexes substrates for recombinant human RNase H1 under multiple-turnover kinetics suggesting that the endogenous enzyme functions under similar kinetic parameters in cells and in the cell-free system. These results provide a blueprint for design of more potent and more specific ASOs.

  7. TARGETED AND OFF-TARGET (BYSTANDER AND ABSCOPAL) EFFECTS OF RADIATION THERAPY: REDOX MECHANISMS AND RISK-BENEFIT ANALYSIS.

    Science.gov (United States)

    Pouget, Jean-Pierre; Georgakilas, Alexandros G; Ravanat, Jean-Luc

    2018-01-19

    Radiation therapy (from external beams to unsealed and sealed radionuclide sources) takes advantage of the detrimental effects of the clustered production of radicals and reactive oxygen species (ROS). Research has mainly focused on the interaction of radiation with water, which is the major constituent of living beings, and with nuclear DNA, which contains the genetic information. This led to the so-called "target" theory according to which cells have to be hit by ionizing particles to elicit an important biological response, including cell death. In cancer therapy, the Poisson law and linear quadratic mathematical models have been used to describe the probability of hits per cell as a function of the radiation dose. However, in the last twenty years, many studies have shown that radiation generates "danger" signals that propagate from irradiated to non-irradiated cells, leading to bystander and other off-target effects. Like for targeted effects, redox mechanisms play a key role also in off-target effects through transmission of ROS and reactive nitrogen species (RNS), but also of cytokines, ATP and extracellular DNA. Particularly, nuclear factor kappa B is essential for triggering self-sustained production of ROS and RNS, thus making the bystander response similar to inflammation. In some therapeutic situations, this phenomenon is associated with recruitment of immune cells that are involved in distant irradiation effects (called "away-from-target" i.e. abscopal effects). Determining the contribution of targeted and off-target effects in the clinic is still challenging. This has important consequences in radiotherapy, but also possibly in diagnostic procedures and in radiation protection.

  8. Expression of growth factor receptors and targeting of EGFR in cholangiocarcinoma cell lines

    International Nuclear Information System (INIS)

    Xu, Ling; Hausmann, Martin; Dietmaier, Wolfgang; Kellermeier, Silvia; Pesch, Theresa; Stieber-Gunckel, Manuela; Lippert, Elisabeth; Klebl, Frank; Rogler, Gerhard

    2010-01-01

    Cholangiocarcinoma (CC) is a malignant neoplasm of the bile ducts or the gallbladder. Targeting of growth factor receptors showed therapeutic potential in palliative settings for many solid tumors. The aim of this study was to determine the expression of seven growth factor receptors in CC cell lines and to assess the effect of blocking the EGFR receptor in vitro. Expression of EGFR (epithelial growth factor receptor), HGFR (hepatocyte growth factor receptor) IGF1R (insulin-like growth factor 1 receptor), IGF2R (insulin-like growth factor 2 receptor) and VEGFR1-3 (vascular endothelial growth factor receptor 1-3) were examined in four human CC cell lines (EGI-1, HuH28, OZ and TFK-1). The effect of the anti-EGFR-antibody cetuximab on cell growth and apoptosis was studied and cell lines were examined for KRAS mutations. EGFR, HGFR and IGFR1 were present in all four cell lines tested. IGFR2 expression was confirmed in EGI-1 and TFK-1. No growth-inhibitory effect was found in EGI-1 cells after incubation with cetuximab. Cetuximab dose-dependently inhibited growth in TFK-1. Increased apoptosis was only seen in TFK-1 cells at the highest cetuximab dose tested (1 mg/ml), with no dose-response-relationship at lower concentrations. In EGI-1 a heterozygous KRAS mutation was found in codon 12 (c.35G>A; p.G12D). HuH28, OZ and TFK-1 lacked KRAS mutation. CC cell lines express a pattern of different growth receptors in vitro. Growth factor inhibitor treatment could be affected from the KRAS genotype in CC. The expression of EGFR itself does not allow prognoses on growth inhibition by cetuximab

  9. Trial Characteristics as Contextual Factors when Evaluating Targeted Therapies in Patients with Psoriatic Disease

    DEFF Research Database (Denmark)

    Ballegaard, Christine; Jørgensen, Tanja S; Skougaard, Marie

    2018-01-01

    characteristics in stratified and meta-regression analyses. Odds ratios (OR) were calculated and compared among the trial eligibility criteria via the Ratio of Odds Ratios (ROR). RESULTS: Forty-eight PsA and psoriasis trials (51 comparisons, 17,737 patients) were eligible. Overall retention was OR 2.16 (1.70 to 2.......75) with higher odds for PsA trials compared with psoriasis trials (ROR = 2.55 [1.64 to 3.97]). The eligibility criteria "targeted therapy history", "minimum required disease duration", "required negative rheumatoid factor", and "required CASPAR criteria" were of importance for achieving ACR20 in Ps...

  10. Targeting the Central Pocket in Human Transcription Factor TEAD as a Potential Cancer Therapeutic Strategy

    OpenAIRE

    Pobbati, Ajaybabu V.; Han, Xiao; Hung, Alvin W.; Weiguang, Seetoh; Huda, Nur; Chen, Guo-Ying; Kang, CongBao; Chia, Cheng San Brian; Luo, Xuelian; Hong, Wanjin; Poulsen, Anders

    2015-01-01

    The human TEAD family of transcription factors (TEAD1-4) is required for YAP-mediated transcription in the Hippo pathway. Hyperactivation of TEAD’s co-activator YAP contributes to tissue overgrowth and human cancers, suggesting that pharmacological interference of TEAD-YAP activity may be an effective strategy for anticancer therapy. Here we report the discovery of a central pocket in the YAP-binding domain (YBD) of TEAD that is targetable by small molecule inhibitors. Our X-ray crystallograp...

  11. Regulation of Small RNAs and Corresponding Targets in Nod Factor-Induced Phaseolus vulgaris Root Hair Cells.

    Science.gov (United States)

    Formey, Damien; Martín-Rodríguez, José Ángel; Leija, Alfonso; Santana, Olivia; Quinto, Carmen; Cárdenas, Luis; Hernández, Georgina

    2016-06-04

    A genome-wide analysis identified the set of small RNAs (sRNAs) from the agronomical important legume Phaseolus vulgaris (common bean), including novel P. vulgaris-specific microRNAs (miRNAs) potentially important for the regulation of the rhizobia-symbiotic process. Generally, novel miRNAs are difficult to identify and study because they are very lowly expressed in a tissue- or cell-specific manner. In this work, we aimed to analyze sRNAs from common bean root hairs (RH), a single-cell model, induced with pure Rhizobium etli nodulation factors (NF), a unique type of signal molecule. The sequence analysis of samples from NF-induced and control libraries led to the identity of 132 mature miRNAs, including 63 novel miRNAs and 1984 phasiRNAs. From these, six miRNAs were significantly differentially expressed during NF induction, including one novel miRNA: miR-RH82. A parallel degradome analysis of the same samples revealed 29 targets potentially cleaved by novel miRNAs specifically in NF-induced RH samples; however, these novel miRNAs were not differentially accumulated in this tissue. This study reveals Phaseolus vulgaris-specific novel miRNA candidates and their corresponding targets that meet all criteria to be involved in the regulation of the early nodulation events, thus setting the basis for exploring miRNA-mediated improvement of the common bean-rhizobia symbiosis.

  12. COREnet: The Fusion of Social Network Analysis and Target Audience Analysis

    Science.gov (United States)

    2014-12-01

    be integrated into a HTML5 web-based Target Audience Analysis Worksheet TAAW? D. SCOPE AND METHODOLOGY This is a three-phase capstone project. The...Harrison & S. Huntington (Eds.), Culture matters: How values shape human progress (pp. 98–111). New York: Basic Books Gauchat, J. D., (2012). HTML5 for...networks to inform tactical engagement strategies that will influence the human domain. Small Wars Journal. MacDonald, M. (2012). HTML5 : The

  13. CD4+ T cells targeting dominant and cryptic epitopes from Bacillus anthracis Lethal Factor

    Directory of Open Access Journals (Sweden)

    Stephanie eAscough

    2016-01-01

    Full Text Available Anthrax is an endemic infection in many countries, particularly in the developing world. The causative agent, Bacillus anthracis, mediates disease through the secretion of binary exotoxins. Until recently, research into adaptive immunity targeting this bacterial pathogen has largely focused on the humoral response to these toxins. There is, however, growing recognition that cellular immune responses involving IFNγ producing CD4+ T cells also contribute significantly to a protective memory response. An established concept in adaptive immunity to infection is that during infection of host cells, new microbial epitopes may be revealed, leading to immune recognition of so called ‘cryptic’ or ‘subdominant’ epitopes. We analysed the response to both cryptic and immunodominant T cell epitopes derived from the toxin component lethal factor and presented by a range of HLA-DR alleles. Using IFNγ-ELISPOT assays we characterised epitopes that elicited a response following immunisation with synthetic peptide and the whole protein and tested their capacities to bind purified HLA-DR molecules in vitro. We found that DR1 transgenics demonstrated T cell responses to a greater number of domain III cryptic epitopes than other HLA-DR transgenics, and that this pattern was repeated with the immunodominant epitopes, a greater proportion of these epitopes induced a T cell response when presented within the context of the whole protein. Immunodominant epitopes LF457-476 and LF467-487 were found to induce a T cell response to the peptide, as well as to the whole native LF protein in DR1 and DR15, but not in DR4 trangenics. The analysis of Domain I revealed the presence of several unique cryptic epitopes all of which showed a strong to moderate relative binding affinity to HLA-DR4 molecules. However, none of the cryptic epitopes from either domain III or I displayed notably high binding affinities across all HLA-DR alleles assayed. These responses were

  14. Factor Rotation and Standard Errors in Exploratory Factor Analysis

    Science.gov (United States)

    Zhang, Guangjian; Preacher, Kristopher J.

    2015-01-01

    In this article, we report a surprising phenomenon: Oblique CF-varimax and oblique CF-quartimax rotation produced similar point estimates for rotated factor loadings and factor correlations but different standard error estimates in an empirical example. Influences of factor rotation on asymptotic standard errors are investigated using a numerical…

  15. Sensitivity Analysis of Selected DIVOPS Input Factors

    Science.gov (United States)

    1977-12-01

    v40. .............. o..... ....... H-3 viii CAA- TD -77-9 SENSITIVITY ANALYSIS OF SELECTED DIVOPS INPUT FACTORS CHAPTER 1 INTRODUCTION 1-1. BACKGROUND...u UI 3,743 3,79 3,183 3.790 3,709 J.648 U 1 3,793 J.791 4,74b D 3.703 3.700 3.733 i 3,14U 3,147 3,844 3,0442 3.753 3.751 U 3,406 3,b70 J, IZ4 Jlbd J

  16. Model correction factor method for system analysis

    DEFF Research Database (Denmark)

    Ditlevsen, Ove Dalager; Johannesen, Johannes M.

    2000-01-01

    The Model Correction Factor Method is an intelligent response surface method based on simplifiedmodeling. MCFM is aimed for reliability analysis in case of a limit state defined by an elaborate model. Herein it isdemonstrated that the method is applicable for elaborate limit state surfaces on which...... severallocally most central points exist without there being a simple geometric definition of the corresponding failuremodes such as is the case for collapse mechanisms in rigid plastic hinge models for frame structures. Taking as simplifiedidealized model a model of similarity with the elaborate model...... surface than existing in the idealized model....

  17. Inflation targeting and inflation performance : a comparative analysis

    NARCIS (Netherlands)

    Samarina, Anna; De Haan, Jakob; Terpstra, M.

    2014-01-01

    This article examines how the impact of inflation targeting on inflation performance depends on the choice of country samples, adoption dates, time periods and methodological approaches. We apply two different estimation methods - difference-in-differences and propensity score matching - for our

  18. The insulin-like growth factor (IGF) axis as an anticancer target in prostate cancer.

    Science.gov (United States)

    Heidegger, Isabel; Massoner, Petra; Sampson, Natalie; Klocker, Helmut

    2015-10-28

    Prostate cancer (PCa) is the most common cancer and the second leading cause of cancer death in males. In recent years, several new targeting agents have been introduced for the treatment of advanced stages of the disease. However, development of resistance limits the efficacy of new drugs and there is a further need to develop additional novel treatment approaches. One of the most investigated targets in cancer research is the insulin-like growth factor (IGF) axis, whose receptors are overexpressed in several cancer entities including PCa. In preclinical studies in PCa, targeting of the IGF axis receptors showed promising anti-tumor effects. Currently available data on clinical studies do not meet the expectations for this new treatment approach. In this review we provide a summary of preclinical and clinical studies on the IGF axis in PCa including treatment with monoclonal antibodies and tyrosine kinase inhibitors. Moreover, we summarize preliminary results from ongoing studies and discuss limitations and side effects of the substances used. We also address the role of the IGF axis in the biomarkers setting including IGF-binding proteins and genetic variants. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. Transcription Factor STAT3 as a Novel Molecular Target for Cancer Prevention

    Energy Technology Data Exchange (ETDEWEB)

    Xiong, Ailian; Yang, Zhengduo [Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030 (United States); Shen, Yicheng [College of Natural Sciences, The University of Texas at Austin, Austin, TX 78712 (United States); Zhou, Jia [Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555 (United States); Shen, Qiang, E-mail: qshen@mdanderson.org [Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030 (United States)

    2014-04-16

    Signal Transducers and Activators of Transcription (STATs) are a family of transcription factors that regulate cell proliferation, differentiation, apoptosis, immune and inflammatory responses, and angiogenesis. Cumulative evidence has established that STAT3 has a critical role in the development of multiple cancer types. Because it is constitutively activated during disease progression and metastasis in a variety of cancers, STAT3 has promise as a drug target for cancer therapeutics. Recently, STAT3 was found to have an important role in maintaining cancer stem cells in vitro and in mouse tumor models, suggesting STAT3 is integrally involved in tumor initiation, progression and maintenance. STAT3 has been traditionally considered as nontargetable or undruggable, and the lag in developing effective STAT3 inhibitors contributes to the current lack of FDA-approved STAT3 inhibitors. Recent advances in cancer biology and drug discovery efforts have shed light on targeting STAT3 globally and/or specifically for cancer therapy. In this review, we summarize current literature and discuss the potential importance of STAT3 as a novel target for cancer prevention and of STAT3 inhibitors as effective chemopreventive agents.

  20. Hypoxia-Inducible Factors: Mediators of Cancer Progression; Prognostic and Therapeutic Targets in Soft Tissue Sarcomas

    International Nuclear Information System (INIS)

    Sadri, Navid; Zhang, Paul J.

    2013-01-01

    Soft-tissue sarcomas remain aggressive tumors that result in death in greater than a third of patients due to either loco-regional recurrence or distant metastasis. Surgical resection remains the main choice of treatment for soft tissue sarcomas with pre- and/or post-operational radiation and neoadjuvant chemotherapy employed in more advanced stage disease. However, in recent decades, there has been little progress in the average five-year survival for the majority of patients with high-grade soft tissue sarcomas, highlighting the need for improved targeted therapeutic agents. Clinical and preclinical studies demonstrate that tumor hypoxia and up-regulation of hypoxia-inducible factors (HIFs) is associated with decreased survival, increased metastasis, and resistance to therapy in soft tissue sarcomas. HIF-mediated gene expression regulates many critical aspects of tumor biology, including cell survival, metabolic programming, angiogenesis, metastasis, and therapy resistance. In this review, we discuss HIFs and HIF-mediated genes as potential prognostic markers and therapeutic targets in sarcomas. Many pharmacological agents targeting hypoxia-related pathways are in development that may hold therapeutic potential for treating both primary and metastatic sarcomas that demonstrate increased HIF expression

  1. Transcription Factor STAT3 as a Novel Molecular Target for Cancer Prevention

    International Nuclear Information System (INIS)

    Xiong, Ailian; Yang, Zhengduo; Shen, Yicheng; Zhou, Jia; Shen, Qiang

    2014-01-01

    Signal Transducers and Activators of Transcription (STATs) are a family of transcription factors that regulate cell proliferation, differentiation, apoptosis, immune and inflammatory responses, and angiogenesis. Cumulative evidence has established that STAT3 has a critical role in the development of multiple cancer types. Because it is constitutively activated during disease progression and metastasis in a variety of cancers, STAT3 has promise as a drug target for cancer therapeutics. Recently, STAT3 was found to have an important role in maintaining cancer stem cells in vitro and in mouse tumor models, suggesting STAT3 is integrally involved in tumor initiation, progression and maintenance. STAT3 has been traditionally considered as nontargetable or undruggable, and the lag in developing effective STAT3 inhibitors contributes to the current lack of FDA-approved STAT3 inhibitors. Recent advances in cancer biology and drug discovery efforts have shed light on targeting STAT3 globally and/or specifically for cancer therapy. In this review, we summarize current literature and discuss the potential importance of STAT3 as a novel target for cancer prevention and of STAT3 inhibitors as effective chemopreventive agents

  2. Identification of direct regulatory targets of the transcription factor Sox10 based on function and conservation

    Directory of Open Access Journals (Sweden)

    Lee Sanghyuk

    2008-09-01

    Full Text Available Abstract Background Sox10, a member of the Sry-related HMG-Box gene family, is a critical transcription factor for several important cell lineages, most notably the neural crest stem cells and the derivative peripheral glial cells and melanocytes. Thus far, only a handful of direct target genes are known for this transcription factor limiting our understanding of the biological network it governs. Results We describe identification of multiple direct regulatory target genes of Sox10 through a procedure based on function and conservation. By combining RNA interference technique and DNA microarray technology, we have identified a set of genes that show significant down-regulation upon introduction of Sox10 specific siRNA into Schwannoma cells. Subsequent comparative genomics analyses led to potential binding sites for Sox10 protein conserved across several mammalian species within the genomic region proximal to these genes. Multiple sites belonging to 4 different genes (proteolipid protein, Sox10, extracellular superoxide dismutase, and pleiotrophin were shown to directly interact with Sox10 by chromatin immunoprecipitation assay. We further confirmed the direct regulation through the identified cis-element for one of the genes, extracellular superoxide dismutase, using electrophoretic mobility shift assay and reporter assay. Conclusion In sum, the process of combining differential expression profiling and comparative genomics successfully led to further defining the role of Sox10, a critical transcription factor for the development of peripheral glia. Our strategy utilizing relatively accessible techniques and tools should be applicable to studying the function of other transcription factors.

  3. Disruptive Event Biosphere Dose Conversion Factor Analysis

    International Nuclear Information System (INIS)

    M. Wasiolek

    2004-01-01

    This analysis report is one of the technical reports containing documentation of the Environmental Radiation Model for Yucca Mountain, Nevada (ERMYN), a biosphere model supporting the total system performance assessment (TSPA) for the license application (LA) for the Yucca Mountain repository. This analysis report describes the development of biosphere dose conversion factors (BDCFs) for the volcanic ash exposure scenario, and the development of dose factors for calculating inhalation dose during volcanic eruption. A graphical representation of the documentation hierarchy for the ERMYN is presented in Figure 1-1. This figure shows the interrelationships among the products (i.e., analysis and model reports) developed for biosphere modeling and provides an understanding of how this analysis report contributes to biosphere modeling. This report is one of two reports that develop biosphere BDCFs, which are input parameters for the TSPA model. The ''Biosphere Model Report'' (BSC 2004 [DIRS 169460]) describes in detail the ERMYN conceptual model and mathematical model. The input parameter reports, shown to the right of the Biosphere Model Report in Figure 1-1, contain detailed descriptions of the model input parameters, their development and the relationship between the parameters and specific features, events and processes (FEPs). This report describes biosphere model calculations and their output, the BDCFs, for the volcanic ash exposure scenario. This analysis receives direct input from the outputs of the ''Biosphere Model Report'' (BSC 2004 [DIRS 169460]) and from the five analyses that develop parameter values for the biosphere model (BSC 2004 [DIRS 169671]; BSC 2004 [DIRS 169672]; BSC 2004 [DIRS 169673]; BSC 2004 [DIRS 169458]; and BSC 2004 [DIRS 169459]). The results of this report are further analyzed in the ''Biosphere Dose Conversion Factor Importance and Sensitivity Analysis''. The objective of this analysis was to develop the BDCFs for the volcanic ash

  4. Disruptive Event Biosphere Dose Conversion Factor Analysis

    Energy Technology Data Exchange (ETDEWEB)

    M. Wasiolek

    2004-09-08

    This analysis report is one of the technical reports containing documentation of the Environmental Radiation Model for Yucca Mountain, Nevada (ERMYN), a biosphere model supporting the total system performance assessment (TSPA) for the license application (LA) for the Yucca Mountain repository. This analysis report describes the development of biosphere dose conversion factors (BDCFs) for the volcanic ash exposure scenario, and the development of dose factors for calculating inhalation dose during volcanic eruption. A graphical representation of the documentation hierarchy for the ERMYN is presented in Figure 1-1. This figure shows the interrelationships among the products (i.e., analysis and model reports) developed for biosphere modeling and provides an understanding of how this analysis report contributes to biosphere modeling. This report is one of two reports that develop biosphere BDCFs, which are input parameters for the TSPA model. The ''Biosphere Model Report'' (BSC 2004 [DIRS 169460]) describes in detail the ERMYN conceptual model and mathematical model. The input parameter reports, shown to the right of the Biosphere Model Report in Figure 1-1, contain detailed descriptions of the model input parameters, their development and the relationship between the parameters and specific features, events and processes (FEPs). This report describes biosphere model calculations and their output, the BDCFs, for the volcanic ash exposure scenario. This analysis receives direct input from the outputs of the ''Biosphere Model Report'' (BSC 2004 [DIRS 169460]) and from the five analyses that develop parameter values for the biosphere model (BSC 2004 [DIRS 169671]; BSC 2004 [DIRS 169672]; BSC 2004 [DIRS 169673]; BSC 2004 [DIRS 169458]; and BSC 2004 [DIRS 169459]). The results of this report are further analyzed in the ''Biosphere Dose Conversion Factor Importance and Sensitivity Analysis''. The objective of this

  5. Parental Factors Associated with Child Post-traumatic Stress Following Injury: A Consideration of Intervention Targets

    Directory of Open Access Journals (Sweden)

    Anna E. Wise

    2017-08-01

    Full Text Available Post-traumatic stress disorder (PTSD symptoms are relatively common following pediatric traumatic injury and are related to poor long-term child outcomes. However, due to concerns regarding the efficacy of early child preventive interventions, and difficulty intervening with injured and medicated children soon after the event, it is not feasible to provide early psychological interventions to children exposed to traumatic injury. Parental PTSD symptoms and reactions to the child’s traumatic injury impact child outcomes and provide potential targets for early intervention to reduce child symptom development without involving the child. The authors conducted a review of the literature using Psycinfo and Pubmed research databases (publication years = 1990–2017 and identified 65 published studies relevant to the topic of the review. The present review considers parent factors [parenting styles, parental post-traumatic pathology (PTS, adaptive and maladaptive coping strategies, and communication regarding the traumatic injury] and their impact on child PTS. We focus specifically on factors amenable to intervention. We further review moderators of these relationships (e.g., child age and gender, parent gender and conclude that it is unlikely that a one-size-fits-all approach to treatment will be successful. Rather, it is necessary to consider the age and gender of parent child dyads in designing and providing targeted interventions to families following the traumatic injury of a child.

  6. Targeting Hypoxia-Inducible Factors for the Treatment of Anemia in Chronic Kidney Disease Patients.

    Science.gov (United States)

    Locatelli, Francesco; Fishbane, Steven; Block, Geoffrey A; Macdougall, Iain C

    2017-01-01

    Anemia, a common complication of chronic kidney disease (CKD), has previously been attributed primarily to decreased production of erythropoietin. More recently, it has become apparent that the etiology of anemia involves several other factors, most notably dysfunctional iron metabolism, mediated via increased hepcidin activity and reduced clearance. Current management of anemia in patients with advanced CKD is based on erythropoiesis-stimulating agents and iron supplementation, along with red blood cell transfusions when necessary; however, safety considerations associated with these therapies highlight the need to pursue alternative treatment options targeting other mechanisms such as hypoxia-inducible factors (HIFs) that act as central regulators of erythropoiesis by coordinating a series of graded hypoxic responses. This review discusses the discovery of the HIF pathway and its regulation via HIF prolyl hydroxylase enzymes in the context of erythropoiesis and iron metabolism. The rationale for targeting this pathway and the clinical development of HIF prolyl hydroxylase inhibitors are reviewed, with a commentary on the potential implications of this class of agents in CKD anemia management. Key Messages: Pharmacologic activation of the HIF pathway results in a transient pseudo-hypoxic state that stimulates erythropoiesis in CKD patients with anemia. Results from clinical studies of a number of HIF prolyl hydroxylase inhibitors are increasingly available and provide support for the continued evaluation of the risk-benefit ratio of this novel therapeutic approach to the treatment of anemia in CKD. © 2017 S. Karger AG, Basel.

  7. Targeting the Central Pocket in Human Transcription Factor TEAD as a Potential Cancer Therapeutic Strategy.

    Science.gov (United States)

    Pobbati, Ajaybabu V; Han, Xiao; Hung, Alvin W; Weiguang, Seetoh; Huda, Nur; Chen, Guo-Ying; Kang, CongBao; Chia, Cheng San Brian; Luo, Xuelian; Hong, Wanjin; Poulsen, Anders

    2015-11-03

    The human TEAD family of transcription factors (TEAD1-4) is required for YAP-mediated transcription in the Hippo pathway. Hyperactivation of TEAD's co-activator YAP contributes to tissue overgrowth and human cancers, suggesting that pharmacological interference of TEAD-YAP activity may be an effective strategy for anticancer therapy. Here we report the discovery of a central pocket in the YAP-binding domain (YBD) of TEAD that is targetable by small-molecule inhibitors. Our X-ray crystallography studies reveal that flufenamic acid, a non-steroidal anti-inflammatory drug (NSAID), binds to the central pocket of TEAD2 YBD. Our biochemical and functional analyses further demonstrate that binding of NSAIDs to TEAD inhibits TEAD-YAP-dependent transcription, cell migration, and proliferation, indicating that the central pocket is important for TEAD function. Therefore, our studies discover a novel way of targeting TEAD transcription factors and set the stage for therapeutic development of specific TEAD-YAP inhibitors against human cancers. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Transforming growth factor β activated kinase 1: a potential therapeutic target for rheumatic diseases.

    Science.gov (United States)

    Fechtner, Sabrina; Fox, David A; Ahmed, Salahuddin

    2017-07-01

    Pro-inflammatory cytokines such as IL-1β, IL-6 and TNF-α are central regulators of autoinflammatory diseases. While targeting these cytokines has proven to be a successful clinical strategy, the long-term challenges such as drug resistance, lack of efficacy and poor clinical outcomes in some patients are some of the limitations faced by these therapies. This has ignited strategies to reduce inflammation by potentially targeting a variety of molecules, including cell surface receptors, signalling proteins and/or transcription factors to minimize cytokine-induced inflammation and tissue injury. In this regard, transforming growth factor β activated kinase 1 (TAK1) is activated in the inflammatory signal transduction pathways in response to IL-1β, TNF-α or toll-like receptor stimulation. Because of its ideal position upstream of mitogen-activated protein kinases and the IκB kinase complex in signalling cascades, targeting TAK1 may be an attractive strategy for treating diseases characterized by chronic inflammation. Here, we discuss the emerging role of TAK1 in mediating the IL-1β, TNF-α and toll-like receptor mediated inflammatory responses in diseases such as RA, OA, gout and SS. We also review evidence suggesting that TAK1 inhibition may have potential therapeutic value. Finally, we focus on the current status of the development of TAK1 inhibitors and suggest further opportunities for testing TAK1 inhibitors in rheumatic diseases. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. Pharmacological targeting of the transcription factor SOX18 delays breast cancer in mice

    Science.gov (United States)

    Overman, Jeroen; Fontaine, Frank; Moustaqil, Mehdi; Mittal, Deepak; Sierecki, Emma; Sacilotto, Natalia; Zuegg, Johannes; Robertson, Avril AB; Holmes, Kelly; Salim, Angela A; Mamidyala, Sreeman; Butler, Mark S; Robinson, Ashley S; Lesieur, Emmanuelle; Johnston, Wayne; Alexandrov, Kirill; Black, Brian L; Hogan, Benjamin M; De Val, Sarah; Capon, Robert J; Carroll, Jason S; Bailey, Timothy L; Koopman, Peter; Jauch, Ralf; Smyth, Mark J; Cooper, Matthew A; Gambin, Yann; Francois, Mathias

    2017-01-01

    Pharmacological targeting of transcription factors holds great promise for the development of new therapeutics, but strategies based on blockade of DNA binding, nuclear shuttling, or individual protein partner recruitment have yielded limited success to date. Transcription factors typically engage in complex interaction networks, likely masking the effects of specifically inhibiting single protein-protein interactions. Here, we used a combination of genomic, proteomic and biophysical methods to discover a suite of protein-protein interactions involving the SOX18 transcription factor, a known regulator of vascular development and disease. We describe a small-molecule that is able to disrupt a discrete subset of SOX18-dependent interactions. This compound selectively suppressed SOX18 transcriptional outputs in vitro and interfered with vascular development in zebrafish larvae. In a mouse pre-clinical model of breast cancer, treatment with this inhibitor significantly improved survival by reducing tumour vascular density and metastatic spread. Our studies validate an interactome-based molecular strategy to interfere with transcription factor activity, for the development of novel disease therapeutics. DOI: http://dx.doi.org/10.7554/eLife.21221.001 PMID:28137359

  10. Complexity of CNC transcription factors as revealed by gene targeting of the Nrf3 locus.

    Science.gov (United States)

    Derjuga, Anna; Gourley, Tania S; Holm, Teresa M; Heng, Henry H Q; Shivdasani, Ramesh A; Ahmed, Rafi; Andrews, Nancy C; Blank, Volker

    2004-04-01

    Cap'n'collar (CNC) family basic leucine zipper transcription factors play crucial roles in the regulation of mammalian gene expression and development. To determine the in vivo function of the CNC protein Nrf3 (NF-E2-related factor 3), we generated mice deficient in this transcription factor. We performed targeted disruption of two Nrf3 exons coding for CNC homology, basic DNA-binding, and leucine zipper dimerization domains. Nrf3 null mice developed normally and revealed no obvious phenotypic differences compared to wild-type animals. Nrf3(-/-) mice were fertile, and gross anatomy as well as behavior appeared normal. The mice showed normal age progression and did not show any apparent additional phenotype during their life span. We observed no differences in various blood parameters and chemistry values. We infected wild-type and Nrf3(-/-) mice with acute lymphocytic choriomeningitis virus and found no differences in these animals with respect to their number of virus-specific CD8 and CD4 T cells as well as their B-lymphocyte response. To determine whether the mild phenotype of Nrf3 null animals is due to functional redundancy, we generated mice deficient in multiple CNC factors. Contrary to our expectations, an absence of Nrf3 does not seem to cause additional lethality in compound Nrf3(-/-)/Nrf2(-/-) and Nrf3(-/-)/p45(-/-) mice. We hypothesize that the role of Nrf3 in vivo may become apparent only after appropriate challenge to the mice.

  11. A Review of CEFA Software: Comprehensive Exploratory Factor Analysis Program

    Science.gov (United States)

    Lee, Soon-Mook

    2010-01-01

    CEFA 3.02(Browne, Cudeck, Tateneni, & Mels, 2008) is a factor analysis computer program designed to perform exploratory factor analysis. It provides the main properties that are needed for exploratory factor analysis, namely a variety of factoring methods employing eight different discrepancy functions to be minimized to yield initial…

  12. Network motif-based identification of transcription factor-target gene relationships by integrating multi-source biological data

    Directory of Open Access Journals (Sweden)

    de los Reyes Benildo G

    2008-04-01

    Full Text Available Abstract Background Integrating data from multiple global assays and curated databases is essential to understand the spatio-temporal interactions within cells. Different experiments measure cellular processes at various widths and depths, while databases contain biological information based on established facts or published data. Integrating these complementary datasets helps infer a mutually consistent transcriptional regulatory network (TRN with strong similarity to the structure of the underlying genetic regulatory modules. Decomposing the TRN into a small set of recurring regulatory patterns, called network motifs (NM, facilitates the inference. Identifying NMs defined by specific transcription factors (TF establishes the framework structure of a TRN and allows the inference of TF-target gene relationship. This paper introduces a computational framework for utilizing data from multiple sources to infer TF-target gene relationships on the basis of NMs. The data include time course gene expression profiles, genome-wide location analysis data, binding sequence data, and gene ontology (GO information. Results The proposed computational framework was tested using gene expression data associated with cell cycle progression in yeast. Among 800 cell cycle related genes, 85 were identified as candidate TFs and classified into four previously defined NMs. The NMs for a subset of TFs are obtained from literature. Support vector machine (SVM classifiers were used to estimate NMs for the remaining TFs. The potential downstream target genes for the TFs were clustered into 34 biologically significant groups. The relationships between TFs and potential target gene clusters were examined by training recurrent neural networks whose topologies mimic the NMs to which the TFs are classified. The identified relationships between TFs and gene clusters were evaluated using the following biological validation and statistical analyses: (1 Gene set enrichment

  13. Thermal shock analysis of liquid-mercury spallation target

    CERN Document Server

    Ishikura, S; Futakawa, M; Hino, R; Date, H

    2002-01-01

    The developments of the neutron scattering facilities are carried out under the high-intensity proton accelerator project promoted by JAERI and KEK. To estimate the structural integrity of the heavy liquid-metal (Hg) target used as a spallation neutron source in a MW-class neutron scattering facility, dynamic stress behavior due to the incident of a 1 MW-pulsed proton beam was analyzed by using FEM code. Two-type target containers with semi-cylindrical type and flat-plate type window were used as models for analyses. As a result, it is confirmed that the stress (pressure wave) generated by dynamic thermal shock becomes the largest at the center of window, and the flat-plate type window is more advantageous from the structural viewpoint than the semi-cylindrical type window. It has been understood that the stress generated in the window by the pressure wave can be treated as the secondary stress. (author)

  14. Expression of hypoxia-inducible factor 1 alpha and its downstream targets in fibroepithelial tumors of the breast

    NARCIS (Netherlands)

    Kuijper, Arno; Groep, P. van der; Wall, E. van der; Diest, P.J. van

    2005-01-01

    INTRODUCTION Hypoxia-inducible factor 1 (HIF-1) alpha and its downstream targets carbonic anhydrase IX (CAIX) and vascular endothelial growth factor (VEGF) are key factors in the survival of proliferating tumor cells in a hypoxic microenvironment. We studied the expression and prognostic relevance

  15. Analysis of Mo99 production irradiating 20% U targets

    International Nuclear Information System (INIS)

    Calabrese, C. Ruben; Grant, Carlos R.; Marajofsky, Andres; Parkansky, David G.

    1999-01-01

    At present time, the National Atomic Energy Commission is producing about 800 Ci of Mo99 per week irradiating 90% enriched uranium-aluminum alloy plate targets in the RA-3 reactor, a 5 MW. Mtr type one. In order to change to 20% enriched uranium, and to increase the production to about 3000 Ci per week some configurations were studied with rod and plate geometry with uranium (20% enriched) -aluminum targets. The first case was the irradiation of a plate target element in the normal reactor configuration. Results showed a good efficiency, but both reactivity value and power density were too high. An element with rods was also analyzed, but results showed a poor efficiency, too much aluminum involved in the process, although a low reactivity and an acceptable rod power density. Finally, a solution consisting of plate elements with a Zircaloy cladding was adopted, which has shown not only a good efficiency, but it is also acceptable from the viewpoint of safety, heat transference criteria and feasibility

  16. Compact polarimetric SAR product and calibration considerations for target analysis

    Science.gov (United States)

    Sabry, Ramin

    2016-10-01

    Compact polarimetric (CP) data exploitation is currently of growing interest considering the new generation of such Synthetic Aperture Radar (SAR) systems. These systems offer target detection and classification capabilities comparable to those of polarimetric SARs (PolSAR) with less stringent requirements. A good example is the RADARSAT Constellation Mission (RCM). In this paper, some characteristic CP products are described and effects of CP mode deviation from ideal circular polarization transmit on classifications are modeled. The latter is important for operation of typical CP modes (e.g., RCM). The developed model can be used to estimate the ellipticity variation from CP measured data, and hence, calibrate the classification products.

  17. Analysis of the ball-plate laser fusion target experiments

    International Nuclear Information System (INIS)

    Pan, Y.L.

    1975-01-01

    Two dimensional computer simulation results of the two exploding pusher ball-plate targets are in approximate agreement with the experimental space and time integrated x-ray spectra, x-ray microscope data, neutron yields, and laser energy absorptions. Three parameters were used to characterize the laser absorption due to plasma instabilities. Two dumpall parameters were used to model the energy absorption and a single variable was used to define the electron temperature. The values, as well as the selection procedure for these parameters are discussed

  18. Molecular targets for the therapy of cancer associated with metabolic syndrome (transcription and growth factors).

    Science.gov (United States)

    Yunusova, Natalia V; Kondakova, Irina V; Kolomiets, Larisa A; Afanas'ev, Sergey G; Chernyshova, Alena L; Kudryavtsev, Igor V; Tsydenova, Anastasia A

    2017-11-08

    Metabolic syndrome (MS) is one of the leading risk factors for the development of cardiovascular diseases, type II diabetes mellitus and reproductive system diseases. Currently, not only cardiovascular disease and reproductive history risks related with MS are frequently discussed, but it has been also shown that MS is associated with increased risk of some common cancers (endometrial cancer, postmenopausal breast cancer, colorectal cancer, biliary tract cancers and liver cancer for men). Further studies are required to understand the mechanisms of the involvement of MS components in the pathogenesis of malignant neoplasms. Changes in the expression of transcription and growth factors in the peripheral tissues as well as in cancer tissues of patients with MS were revealed. Transcription factors (AMP-activated protein kinase-1, STAT3, sterol regulatory element-binding protein-1 and peroxisome proliferator-activated receptor-γ), leptin and adiponectin receptors seem to be the most promising molecular targets for the therapy of cancers associated with MS. © 2017 John Wiley & Sons Australia, Ltd.

  19. Community-acquired pneumonia and positive urinary antigen tests: Factors associated with targeted antibiotic therapy.

    Science.gov (United States)

    Mothes, A; Léotard, S; Nicolle, I; Smets, A; Chirio, D; Rotomondo, C; Tiger, F; Del Giudice, P; Perrin, C; Néri, D; Foucault, C; Della Guardia, M; Hyvernat, H; Roger, P-M

    2016-10-01

    The use of rapid microbiological tests is supported by antimicrobial stewardship policies. Targeted antibiotic therapy (TAT) for community-acquired pneumonia (CAP) with positive urinary antigen test (UAT) has been associated with a favorable impact on outcome. We aimed to determine the factors associated with TAT prescription. We conducted a retrospective multicenter study including all patients presenting with CAP and positive UAT for Streptococcus pneumoniae or Legionella pneumophila from January 2010 to December 2013. Patients presenting with aspiration pneumonia, coinfection, and neutropenia were excluded. CAP severity was assessed using the Pneumonia Severity Index (PSI). TAT was defined as the administration of amoxicillin for pneumococcal infection and either macrolides or fluoroquinolones (inactive against S. pneumoniae) for Legionella infection. A total of 861 patients were included, including 687 pneumococcal infections and 174 legionellosis from eight facilities and 37 medical departments. TAT was prescribed to 273 patients (32%). Four factors were found independently associated with a lower rate of TAT: a PSI score≥4 (OR 0.37), Hospital A (OR 0.41), hospitalization in the intensive care unit (OR 0.44), and cardiac comorbidities (OR 0.60). Four other factors were associated with a high rate of TAT: positive blood culture for S. pneumoniae (OR 2.32), Hospitals B (OR 2.34), E (OR 2.68), and H (OR 9.32). TAT in CAP with positive UAT was related to the hospitals as well as to patient characteristics. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  20. Anxiety sensitivity and working memory capacity: Risk factors and targets for health behavior promotion.

    Science.gov (United States)

    Otto, Michael W; Eastman, Abraham; Lo, Stephen; Hearon, Bridget A; Bickel, Warren K; Zvolensky, Michael; Smits, Jasper A J; Doan, Stacey N

    2016-11-01

    Understanding the nature and influence of specific risk profiles is increasingly important for health behavior promotion. The purpose of this article is to document the value of two factors-anxiety sensitivity (AS) and working memory capacity (WMC)-for enhancing risk for the initiation and/or maintenance of a range of negative health behaviors. AS is a distress-related risk factor that potentiates avoidance/coping motivations for negative health behaviors. Stress provides the conditions for negative somatic and affective states, and AS amplifies the aversiveness of these experiences and correspondingly hinders adaptive functioning. In contrast, low WMC is hypothesized to exert its effect by decreasing the capacity to filter out current temptations, attenuating a focus on longer-term goals and impairing the application of relevant coping skills at times of stress. In this review, we provide conceptual models for the separate roles of high AS and low WMC in negative health behaviors, review the influence of these factors on specific health behavior exemplars (eating behaviors/obesity, physical activity, smoking, alcohol use, and sleep promotion), provide preliminary evidence for their value as independent treatment targets for health-behavior promotion, and encourage specific research directions in relation to these variables. Copyright © 2016. Published by Elsevier Ltd.

  1. Transcription Factors Expressed in Lateral Organ Boundaries: Identification of Downstream Targets

    Energy Technology Data Exchange (ETDEWEB)

    Springer, Patricia S

    2010-07-12

    The processes of lateral organ initiation and patterning are central to the generation of mature plant form. Characterization of the molecular mechanisms underlying these processes is essential to our understanding of plant development. Communication between the shoot apical meristem and initiating organ primordia is important both for functioning of the meristem and for proper organ patterning, and very little is known about this process. In particular, the boundary between meristem and leaf is emerging as a critical region that is important for SAM maintenance and regulation of organogenesis. The goal of this project was to characterize three boundary-expressed genes that encode predicted transcription factors. Specifically, we have studied LATERAL ORGAN BOUNDARIES (LOB), LATERAL ORGAN FUSION1 (LOF1), and LATERAL ORGAN FUSION2 (LOF2). LOB encodes the founding member of the LOB-DOMAIN (LBD) plant-specific DNA binding transcription factor family and LOF1 and LOF2 encode paralogous MYB-domain transcription factors. We characterized the genetic relationship between these three genes and other boundary and meristem genes. We also used an ectopic inducible expression system to identify direct targets of LOB.

  2. Sustainable Process Design under uncertainty analysis: targeting environmental indicators

    DEFF Research Database (Denmark)

    L. Gargalo, Carina; Gani, Rafiqul

    2015-01-01

    This study focuses on uncertainty analysis of environmental indicators used to support sustainable process design efforts. To this end, the Life Cycle Assessment methodology is extended with a comprehensive uncertainty analysis to propagate the uncertainties in input LCA data to the environmental...

  3. Physiological Factors Analysis in Unpressurized Aircraft Cabins

    Science.gov (United States)

    Patrao, Luis; Zorro, Sara; Silva, Jorge

    2016-11-01

    Amateur and sports flight is an activity with growing numbers worldwide. However, the main cause of flight incidents and accidents is increasingly pilot error, for a number of reasons. Fatigue, sleep issues and hypoxia, among many others, are some that can be avoided, or, at least, mitigated. This article describes the analysis of psychological and physiological parameters during flight in unpressurized aircraft cabins. It relates cerebral oximetry and heart rate with altitude, as well as with flight phase. The study of those parameters might give clues on which variations represent a warning sign to the pilot, thus preventing incidents and accidents due to human factors. Results show that both cerebral oximetry and heart rate change along the flight and altitude in the alert pilot. The impaired pilot might not reveal these variations and, if this is detected, he can be warned in time.

  4. Targeting insulin-like growth factor 1 leads to amelioration of inflammatory demyelinating disease.

    Directory of Open Access Journals (Sweden)

    Matthew F Cusick

    Full Text Available In patients with multiple sclerosis (MS and in mice with experimental autoimmune encephalomyelitis (EAE, proliferating autoreactive T cells play an important role in the pathogenesis of the disease. Due to the importance of these myelin-specific T cells, these cells have been therapeutic targets in a variety of treatments. Previously we found that Lenaldekar (LDK, a novel small molecule, could inhibit exacerbations in a preclinical model of MS when given at the start of an EAE exacerbation. In those studies, we found that LDK could inhibit human T cell recall responses and murine myelin responses in vitro. In these new studies, we found that LDK could inhibit myelin specific T cell responses through the insulin-like growth factor-1 receptor (IGF-1R pathway. Alteration of this pathway led to marked reduction in T cell proliferation and expansion. Blocking this pathway could account for the observed decreases in clinical signs and inflammatory demyelinating disease, which was accompanied by axonal preservation. Our data indicate that IGF-1R could be a potential target for new therapies for the treatment of autoimmune diseases where autoreactive T cell expansion is a requisite for disease.

  5. HSV usurps eukaryotic initiation factor 3 subunit M for viral protein translation: novel prevention target.

    Directory of Open Access Journals (Sweden)

    Natalia Cheshenko

    2010-07-01

    Full Text Available Prevention of genital herpes is a global health priority. B5, a recently identified ubiquitous human protein, was proposed as a candidate HSV entry receptor. The current studies explored its role in HSV infection. Viral plaque formation was reduced by approximately 90% in human cells transfected with small interfering RNA targeting B5 or nectin-1, an established entry receptor. However, the mechanisms were distinct. Silencing of nectin-1 prevented intracellular delivery of viral capsids, nuclear transport of a viral tegument protein, and release of calcium stores required for entry. In contrast, B5 silencing had no effect on these markers of entry, but inhibited viral protein translation. Specifically, viral immediate early genes, ICP0 and ICP4, were transcribed, polyadenylated and transported from the nucleus to the cytoplasm, but the viral transcripts did not associate with ribosomes or polysomes in B5-silenced cells. In contrast, immediate early gene viral transcripts were detected in polysome fractions isolated from control cells. These findings are consistent with sequencing studies demonstrating that B5 is eukaryotic initiation factor 3 subunit m (eIF3m. Although B5 silencing altered the polysome profile of cells, silencing had little effect on cellular RNA or protein expression and was not cytotoxic, suggesting that this subunit is not essential for host cellular protein synthesis. Together these results demonstrate that B5 plays a major role in the initiation of HSV protein translation and could provide a novel target for strategies to prevent primary and recurrent herpetic disease.

  6. Comprehensive reanalysis of transcription factor knockout expression data in Saccharomyces cerevisiae reveals many new targets.

    Science.gov (United States)

    Reimand, Jüri; Vaquerizas, Juan M; Todd, Annabel E; Vilo, Jaak; Luscombe, Nicholas M

    2010-08-01

    Transcription factor (TF) perturbation experiments give valuable insights into gene regulation. Genome-scale evidence from microarray measurements may be used to identify regulatory interactions between TFs and targets. Recently, Hu and colleagues published a comprehensive study covering 269 TF knockout mutants for the yeast Saccharomyces cerevisiae. However, the information that can be extracted from this valuable dataset is limited by the method employed to process the microarray data. Here, we present a reanalysis of the original data using improved statistical techniques freely available from the BioConductor project. We identify over 100,000 differentially expressed genes-nine times the total reported by Hu et al. We validate the biological significance of these genes by assessing their functions, the occurrence of upstream TF-binding sites, and the prevalence of protein-protein interactions. The reanalysed dataset outperforms the original across all measures, indicating that we have uncovered a vastly expanded list of relevant targets. In summary, this work presents a high-quality reanalysis that maximizes the information contained in the Hu et al. compendium. The dataset is available from ArrayExpress (accession: E-MTAB-109) and it will be invaluable to any scientist interested in the yeast transcriptional regulatory system.

  7. A mammalian transcription factor-specific peptide repository for targeted proteomics.

    Science.gov (United States)

    Simicevic, Jovan; Moniatte, Marc; Hamelin, Romain; Ahrné, Erik; Deplancke, Bart

    2015-02-01

    Site-specific transcription factors (TFs) play an essential role in mammalian development and function as they are vital for the majority of cellular processes. Despite their biological importance, TF proteomic data is scarce in the literature, likely due to difficulties in detecting peptides as the abundance of TFs in cells tends to be low. In recent years, significant improvements in MS-based technologies in terms of sensitivity and specificity have increased the interest in developing quantitative methodologies specifically targeting relatively lowly abundant proteins such as TFs in mammalian models. Such efforts would be greatly aided by the availability of TF peptide-specific information as such data would not only enable improvements in speed and accuracy of protein identifications, but also ameliorate cross-comparisons of quantitative proteomics data and allow for a more efficient development of targeted proteomics assays. However, to date, no comprehensive TF proteotypic peptide database has been developed. To address this evident lack of TF peptide data in public repositories, we are generating a comprehensive, experimentally derived TF proteotypic peptide spectral library dataset based on in vitro protein expression. Our library currently contains peptide information for 89 TFs and this number is set to increase in the near future. All MS data have been deposited in the ProteomeXchange with identifier PXD001212 (http://proteomecentral.proteomexchange.org/dataset/PXD001212). © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. An Interbacterial NAD(P)+ Glycohydrolase Toxin Requires Elongation Factor Tu for Delivery to Target Cells

    Energy Technology Data Exchange (ETDEWEB)

    Whitney, John C.; Quentin, Dennis; Sawai, Shin; LeRoux, Michele; Harding, Brittany N.; Ledvina, Hannah E.; Tran, Bao Q.; Robinson, Howard; Goo, Young Ah; Goodlett, David R.; Raunser, Stefan; Mougous, Joseph D.

    2015-10-08

    Type VI secretion (T6S) influences the composition of microbial communities by catalyzing the delivery of toxins between adjacent bacterial cells. Here, we demonstrate that a T6S integral membrane toxin from Pseudomonas aeruginosa, Tse6, acts on target cells by degrading the universally essential dinucleotides NAD+ and NADP+. Structural analyses of Tse6 show that it resembles mono-ADP-ribosyltransferase proteins, such as diphtheria toxin, with the exception of a unique loop that both excludes proteinaceous ADP-ribose acceptors and contributes to hydrolysis. We find that entry of Tse6 into target cells requires its binding to an essential housekeeping protein, translation elongation factor Tu (EF-Tu). These proteins participate in a larger assembly that additionally directs toxin export and provides chaperone activity. Visualization of this complex by electron microscopy defines the architecture of a toxin-loaded T6S apparatus and provides mechanistic insight into intercellular membrane protein delivery between bacteria.

  9. Targeting the Hippo Pathway and Cancer through the TEAD Family of Transcription Factors.

    Science.gov (United States)

    Holden, Jeffrey K; Cunningham, Christian N

    2018-03-20

    The Hippo pathway is a critical transcriptional signaling pathway that regulates cell growth, proliferation and organ development. The transcriptional enhanced associate domain (TEAD) protein family consists of four paralogous transcription factors that function to modulate gene expression in response to the Hippo signaling pathway. Transcriptional activation of these proteins occurs upon binding to the co-activator YAP/TAZ whose entry into the nucleus is regulated by Lats1/2 kinase. In recent years, it has become apparent that the dysregulation and/or overexpression of Hippo pathway effectors is implicated in a wide range of cancers, including prostate, gastric and liver cancer. A large body of work has been dedicated to understanding the therapeutic potential of modulating the phosphorylation and localization of YAP/TAZ. However, YAP/TAZ are considered to be natively unfolded and may be intractable as drug targets. Therefore, TEAD proteins present themselves as an excellent therapeutic target for intervention of the Hippo pathway. This review summarizes the functional role of TEAD proteins in cancer and assesses the therapeutic potential of antagonizing TEAD function in vivo.

  10. Targeting the Hippo Pathway and Cancer through the TEAD Family of Transcription Factors

    Directory of Open Access Journals (Sweden)

    Jeffrey K. Holden

    2018-03-01

    Full Text Available The Hippo pathway is a critical transcriptional signaling pathway that regulates cell growth, proliferation and organ development. The transcriptional enhanced associate domain (TEAD protein family consists of four paralogous transcription factors that function to modulate gene expression in response to the Hippo signaling pathway. Transcriptional activation of these proteins occurs upon binding to the co-activator YAP/TAZ whose entry into the nucleus is regulated by Lats1/2 kinase. In recent years, it has become apparent that the dysregulation and/or overexpression of Hippo pathway effectors is implicated in a wide range of cancers, including prostate, gastric and liver cancer. A large body of work has been dedicated to understanding the therapeutic potential of modulating the phosphorylation and localization of YAP/TAZ. However, YAP/TAZ are considered to be natively unfolded and may be intractable as drug targets. Therefore, TEAD proteins present themselves as an excellent therapeutic target for intervention of the Hippo pathway. This review summarizes the functional role of TEAD proteins in cancer and assesses the therapeutic potential of antagonizing TEAD function in vivo.

  11. Targeted release of transcription factors for cell reprogramming by a natural micro-syringe.

    Science.gov (United States)

    Berthoin, Lionel; Toussaint, Bertrand; Garban, Frédéric; Le Gouellec, Audrey; Caulier, Benjamin; Polack, Benoît; Laurin, David

    2016-11-20

    Ectopic expression of defined transcription factors (TFs) for cell fate handling has proven high potential interest in reprogramming differentiated cells, in particular for regenerative medicine, ontogenesis study and cell based modelling. Pluripotency or transdifferentiation induction as TF mediated differentiation is commonly produced by transfer of genetic information with safety concerns. The direct delivery of proteins could represent a safer alternative but still needs significant advances to be efficient. We have successfully developed the direct delivery of proteins by an attenuated bacterium with a type 3 secretion system that does not require challenging and laborious steps for production and purification of recombinant molecules. Here we show that this natural micro-syringe is able to inject TFs to primary human fibroblasts and cord blood CD34 + hematopoietic stem cells. The signal sequence for vectorization of the TF Oct4 has no effect on DNA binding to its nucleic target. As soon as one hour after injection, vectorized TFs are detectable in the nucleus. The injection process is not associated with toxicity and the bacteria can be completely removed from cell cultures. A three days targeted release of Oct4 or Sox2 embryonic TFs results in the induction of the core pluripotency genes expression in fibroblasts and CD34 + hematopoietic stem cells. This micro-syringe vectorization represents a new strategy for TF delivery and has potential applications for cell fate reprogramming. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. A single gene target of an ETS-family transcription factor determines neuronal CO2-chemosensitivity.

    Directory of Open Access Journals (Sweden)

    Julia P Brandt

    Full Text Available Many animals possess neurons specialized for the detection of carbon dioxide (CO(2, which acts as a cue to elicit behavioral responses and is also an internally generated product of respiration that regulates animal physiology. In many organisms how such neurons detect CO(2 is poorly understood. We report here a mechanism that endows C. elegans neurons with the ability to detect CO(2. The ETS-5 transcription factor is necessary for the specification of CO(2-sensing BAG neurons. Expression of a single ETS-5 target gene, gcy-9, which encodes a receptor-type guanylate cyclase, is sufficient to bypass a requirement for ets-5 in CO(2-detection and transforms neurons into CO(2-sensing neurons. Because ETS-5 and GCY-9 are members of gene families that are conserved between nematodes and vertebrates, a similar mechanism might act in the specification of CO(2-sensing neurons in other phyla.

  13. Bookmarking target genes in mitosis: a shared epigenetic trait of phenotypic transcription factors and oncogenes?

    Science.gov (United States)

    Zaidi, Sayyed K; Grandy, Rodrigo A; Lopez-Camacho, Cesar; Montecino, Martin; van Wijnen, Andre J; Lian, Jane B; Stein, Janet L; Stein, Gary S

    2014-01-15

    The regulatory information for phenotype, proliferation, and growth of normal and tumor cells must be maintained through genome replication in the S phase and cell division during mitosis. Epigenetic mechanisms that include DNA methylation, posttranslational modifications of histones, selective utilization of histone variants, and inheritable RNA molecules play pivotal roles in maintaining cellular identity through mitotic divisions. Recent studies demonstrate that mitotic occupancy of genes, which are determinants of cell fate, growth, and proliferation, by lineage-restricted transcription factors is a key epigenetic mechanism for retention and transmission of cellular expression memory. Evidence is emerging for the presence of distinct transcriptional regulatory microenvironments in mitotic chromosomes in which the genes bookmarked for reactivation postmitotically reside. Importantly, some oncoproteins are present in mitotic microenvironments where they occupy target genes during mitosis and may contribute to perpetuating the transformed phenotype. We discuss emerging regulatory implications of epigenetically bookmarking genes during mitosis for physiologic control as well as for the onset and progression of cancer.

  14. Single base mismatches in the mRNA target site allow specific seed region-mediated off-target binding of siRNA targeting human coagulation factor 7.

    Science.gov (United States)

    Ravon, Morgane; Berrera, Marco; Ebeling, Martin; Certa, Ulrich

    2012-01-01

    We have analyzed the off-target activity of two siRNAs (F7-1, F7-2) that knock-down human blood coagulation factor 7 mRNA. F7-1 modulates a significant number of non-target transcripts while F7-2 shows high selectivity for the target transcript under various experimental conditions. The 3'-UTRs of all F7-1 off-target genes show statistically significant enrichment of the reverse complement of the F7-1 siRNA seed region located in the guide strand. Seed region enrichment was confirmed in off-target transcripts modulated by siRNA targeting the glucocorticoid receptor. To investigate how these sites contribute to off-target recognition of F7-1, we employed CXCL5 transcript as model system because it contains five F7-1 seed sequence motifs with single base mismatches. We show by transient transfection of reporter gene constructs into HEK293 cells that three out of five sites located in the 3'-UTR region are required for F7-1 off-target activity. For further mechanistic dissection, the sequences of these sites were synthesized and inserted either individually or joined in dimeric or trimeric constructs. Only the fusion constructs were silenced by F7-1 while the individual sites had no off-target activity. Based on F7-1 as a model, a single mismatch between the siRNA seed region and mRNA target sites is tolerated for target recognition and the CXCL5 data suggest a requirement for binding to multiple target sites in off-target transcripts.

  15. Thermal analysis of titanium drive-in target for D-D neutron generation.

    Science.gov (United States)

    Jung, N S; Kim, I J; Kim, S J; Choi, H D

    2010-01-01

    Thermal analysis was performed for a titanium drive-in target of a D-D neutron generator. Computational fluid dynamics code CFX-5 was used in this study. To define the heat flux term for the thermal analysis, beam current profile was measured. Temperature of the target was calculated at some of the operating conditions. The cooling performance of the target was evaluated by means of the comparison of the calculated maximum target temperature and the critical temperature of titanium. Copyright 2009 Elsevier Ltd. All rights reserved.

  16. Cholesterol Sulfate and Cholesterol Sulfotransferase Inhibit Gluconeogenesis by Targeting Hepatocyte Nuclear Factor

    Science.gov (United States)

    Shi, Xiongjie; Cheng, Qiuqiong; Xu, Leyuan; Yan, Jiong; Jiang, Mengxi; He, Jinhan; Xu, Meishu; Stefanovic-Racic, Maja; Sipula, Ian; O'Doherty, Robert Martin; Ren, Shunlin

    2014-01-01

    Sulfotransferase (SULT)-mediated sulfation represents a critical mechanism in regulating the chemical and functional homeostasis of endogenous and exogenous molecules. The cholesterol sulfotransferase SULT2B1b catalyzes the sulfoconjugation of cholesterol to synthesize cholesterol sulfate (CS). In this study, we showed that the expression of SULT2B1b in the liver was induced in obese mice and during the transition from the fasted to the fed state, suggesting that the regulation of SULT2B1b is physiologically relevant. CS and SULT2B1b inhibited gluconeogenesis by targeting the gluconeogenic factor hepatocyte nuclear factor 4α (HNF4α) in both cell cultures and transgenic mice. Treatment of mice with CS or transgenic overexpression of the CS-generating enzyme SULT2B1b in the liver inhibited hepatic gluconeogenesis and alleviated metabolic abnormalities both in mice with diet-induced obesity (DIO) and in leptin-deficient (ob/ob) mice. Mechanistically, CS and SULT2B1b inhibited gluconeogenesis by suppressing the expression of acetyl coenzyme A (acetyl-CoA) synthetase (Acss), leading to decreased acetylation and nuclear exclusion of HNF4α. Our results also suggested that leptin is a potential effector of SULT2B1b in improving metabolic function. We conclude that SULT2B1b and its enzymatic by-product CS are important metabolic regulators that control glucose metabolism, suggesting CS as a potential therapeutic agent and SULT2B1b as a potential therapeutic target for metabolic disorders. PMID:24277929

  17. Thermal-hydraulic analysis of LBE spallation target for accelerator ...

    Indian Academy of Sciences (India)

    In an accelerator-driven subcritical system (ADS), a high-performance spallation neutron source is used to feed the subcritical reactor. Neutron generation depends on the proton beam intensity. If the beam intensity is increased by a given factor, the number of generated neutrons will increase. The mechanism yielding a ...

  18. Micro-Doppler Analysis of Rotating Target in SAR

    National Research Council Canada - National Science Library

    Thayaparan, T; Abrol, S; Qian, S

    2005-01-01

    .... The phase modulation may be seen as a time-dependent micro-Doppler (m-D) frequency. Due to their superior resolution potential, it is useful to analyze such signals with time-frequency analysis methods...

  19. Expresso: A database and web server for exploring the interaction of transcription factors and their target genes inArabidopsis thalianausing ChIP-Seq peak data.

    Science.gov (United States)

    Aghamirzaie, Delasa; Raja Velmurugan, Karthik; Wu, Shuchi; Altarawy, Doaa; Heath, Lenwood S; Grene, Ruth

    2017-01-01

    Motivation: The increasing availability of chromatin immunoprecipitation sequencing (ChIP-Seq) data enables us to learn more about the action of transcription factors in the regulation of gene expression. Even though in vivo transcriptional regulation often involves the concerted action of more than one transcription factor, the format of each individual ChIP-Seq dataset usually represents the action of a single transcription factor. Therefore, a relational database in which available ChIP-Seq datasets are curated is essential. Results: We present Expresso (database and webserver) as a tool for the collection and integration of available Arabidopsis ChIP-Seq peak data, which in turn can be linked to a user's gene expression data. Known target genes of transcription factors were identified by motif analysis of publicly available GEO ChIP-Seq data sets. Expresso currently provides three services: 1) Identification of target genes of a given transcription factor; 2) Identification of transcription factors that regulate a gene of interest; 3) Computation of correlation between the gene expression of transcription factors and their target genes. Availability : Expresso is freely available at http://bioinformatics.cs.vt.edu/expresso/.

  20. Evaluating Transcription Factor Activity Changes by Scoring Unexplained Target Genes in Expression Data.

    Directory of Open Access Journals (Sweden)

    Evi Berchtold

    Full Text Available Several methods predict activity changes of transcription factors (TFs from a given regulatory network and measured expression data. But available gene regulatory networks are incomplete and contain many condition-dependent regulations that are not relevant for the specific expression measurement. It is not known which combination of active TFs is needed to cause a change in the expression of a target gene. A method to systematically evaluate the inferred activity changes is missing. We present such an evaluation strategy that indicates for how many target genes the observed expression changes can be explained by a given set of active TFs. To overcome the problem that the exact combination of active TFs needed to activate a gene is typically not known, we assume a gene to be explained if there exists any combination for which the predicted active TFs can possibly explain the observed change of the gene. We introduce the i-score (inconsistency score, which quantifies how many genes could not be explained by the set of activity changes of TFs. We observe that, even for these minimal requirements, published methods yield many unexplained target genes, i.e. large i-scores. This holds for all methods and all expression datasets we evaluated. We provide new optimization methods to calculate the best possible (minimal i-score given the network and measured expression data. The evaluation of this optimized i-score on a large data compendium yields many unexplained target genes for almost every case. This indicates that currently available regulatory networks are still far from being complete. Both the presented Act-SAT and Act-A* methods produce optimal sets of TF activity changes, which can be used to investigate the difficult interplay of expression and network data. A web server and a command line tool to calculate our i-score and to find the active TFs associated with the minimal i-score is available from https://services.bio.ifi.lmu.de/i-score.

  1. An Analysis of Determinants of Under-5 Mortality across Countries: Defining Priorities to Achieve Targets in Sustainable Developmental Goals.

    Science.gov (United States)

    Acheampong, Michael; Ejiofor, Chukwudi; Salinas-Miranda, Abraham

    2017-06-01

    Objectives The end of the era of millennium development goals (MDGs) ushered in the sustainable development goals (SDGs) with a new target for the reduction of under-five mortality rates (U5MR). Although U5MR decreased globally, the reduction was insufficient to meet MDGs targets because significant socioeconomic inequities remain unaddressed across and within countries. Thus, further progress in achieving the new SDGs target will be hindered if there is no adequate prioritization of important socioeconomic, healthcare, and environmental factors. The objective of this study was to assess factors that account most for the differences in U5MR between countries around the globe. Methods We conducted an ordinary least squares (OLS) regression-based prioritization analysis of socioeconomic, healthcare, and environmental variables from 109 countries to understand which factors explain the differences in U5MR best. Results All indicators examined individually affected differences in U5MR between countries. However, the results of multivariate OLS regression showed that the most important factors that accounted for the differences were, in order: fertility rate, total health expenditure per capita, access to improved water and sanitation, and female employment rate. Conclusions To achieve the new global target for U5MR, policymakers must focus on certain priority areas, such as interventions that address access to affordable maternal healthcare services, educational programs for mothers, especially those who are adolescents, and safe drinking water and sanitation.

  2. Practical Considerations for Using Exploratory Factor Analysis in Educational Research

    Science.gov (United States)

    Beavers, Amy S.; Lounsbury, John W.; Richards, Jennifer K.; Huck, Schuyler W.; Skolits, Gary J.; Esquivel, Shelley L.

    2013-01-01

    The uses and methodology of factor analysis are widely debated and discussed, especially the issues of rotational use, methods of confirmatory factor analysis, and adequate sample size. The variety of perspectives and often conflicting opinions can lead to confusion among researchers about best practices for using factor analysis. The focus of the…

  3. Time Series Factor Analysis with an Application to Measuring Money

    NARCIS (Netherlands)

    Gilbert, Paul D.; Meijer, Erik

    2005-01-01

    Time series factor analysis (TSFA) and its associated statistical theory is developed. Unlike dynamic factor analysis (DFA), TSFA obviates the need for explicitly modeling the process dynamics of the underlying phenomena. It also differs from standard factor analysis (FA) in important respects: the

  4. miR-370 suppresses HBV gene expression and replication by targeting nuclear factor IA.

    Science.gov (United States)

    Fan, Hongxia; Lv, Ping; Lv, Jing; Zhao, Xiaopei; Liu, Min; Zhang, Guangling; Tang, Hua

    2017-05-01

    Hepatitis B virus (HBV) infection is a major health problem worldwide. The roles of microRNAs in the regulation of HBV expression are being increasingly recognized. In this study, we found that overexpression of miR-370 suppressed HBV gene expression and replication in Huh7 cells, whereas antisense knockdown of endogenous miR-370 enhanced HBV gene expression and replication in Huh7 cells and HepG2.2.15 cells. Further, we identified the transcription factor nuclear factor IA (NFIA) as a new host target of miR-370. Overexpression and knockdown studies showed that NFIA stimulated HBV gene expression and replication. Importantly, overexpression of NFIA counteracted the effect of miR-370 on HBV gene expression and replication. Further mechanistic studies showed that miR-370 suppressed HBV replication and gene expression by repressing HBV Enhancer I activity, and one of the NFIA binding site in the Enhancer I element was responsible for the repressive effect of miR-370 on HBV Enhancer I activity. Altogether, our results demonstrated that miR-370 suppressed HBV gene expression and replication through repressing NFIA expression, which stimulates HBV replication via direct regulation on HBV Enhancer I activities. Our findings may provide a new antiviral strategy for HBV infection. J. Med. Virol. 89:834-844, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  5. A Monte Carlo Study of Recovery of Weak Factor Loadings in Confirmatory Factor Analysis

    Science.gov (United States)

    Ximenez, Carmen

    2006-01-01

    The recovery of weak factors has been extensively studied in the context of exploratory factor analysis. This article presents the results of a Monte Carlo simulation study of recovery of weak factor loadings in confirmatory factor analysis under conditions of estimation method (maximum likelihood vs. unweighted least squares), sample size,…

  6. Bioinformatic analysis to discover putative drug targets against ...

    African Journals Online (AJOL)

    /

    2012-01-26

    Jan 26, 2012 ... JVIRTUAL GEL. GELBANK was available from the NCBI FTP server. This website incorporates only completed genomes and information pertinent to 2-DE. Link is available at www.gelbank.anl.gov. JVirGel is a software for the simulation and analysis of proteomics data (http://www.jvirgel.de/). The Java TM.

  7. Meta-analysis of targeted small-group reading interventions.

    Science.gov (United States)

    Hall, Matthew S; Burns, Matthew K

    2018-02-01

    Small-group reading interventions are commonly used in schools but the components that make them effective are still debated or unknown. The current study meta-analyzed 26 small-group reading intervention studies that resulted in 27 effect sizes. Findings suggested a moderate overall effect for small-group reading interventions (weighted g=0.54). Interventions were more effective if they were targeted to a specific skill (g=0.65), then as part of a comprehensive intervention program that addressed multiple skills (g=0.35). There was a small correlation between intervention effects and group size (r=0.21) and duration (r=0.11). Small-group interventions led to a larger median effect size (g=0.64) for elementary-aged students than for those in middle or high school (g=0.20), but the two confidence intervals overlapped. Implications for research and practice are discussed. Copyright © 2017 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.

  8. Structures of mithramycin analogues bound to DNA and implications for targeting transcription factor FLI1.

    Science.gov (United States)

    Hou, Caixia; Weidenbach, Stevi; Cano, Kristin E; Wang, Zhonghua; Mitra, Prithiba; Ivanov, Dmitri N; Rohr, Jürgen; Tsodikov, Oleg V

    2016-10-14

    Transcription factors have been considered undruggable, but this paradigm has been recently challenged. DNA binding natural product mithramycin (MTM) is a potent antagonist of oncogenic transcription factor EWS-FLI1. Structural details of MTM recognition of DNA, including the FLI1 binding sequence GGA(A/T), are needed to understand how MTM interferes with EWS-FLI1. We report a crystal structure of an MTM analogue MTM SA-Trp bound to a DNA oligomer containing a site GGCC, and two structures of a novel analogue MTM SA-Phe in complex with DNA. MTM SA-Phe is bound to sites AGGG and GGGT on one DNA, and to AGGG and GGGA(T) (a FLI1 binding site) on the other, revealing how MTM recognizes different DNA sequences. Unexpectedly, at sub-micromolar concentrations MTMs stabilize FLI1-DNA complex on GGAA repeats, which are critical for the oncogenic function of EWS-FLI1. We also directly demonstrate by nuclear magnetic resonance formation of a ternary FLI1-DNA-MTM complex on a single GGAA FLI1/MTM binding site. These biochemical and structural data and a new FLI1-DNA structure suggest that MTM binds the minor groove and perturbs FLI1 bound nearby in the major groove. This ternary complex model may lead to development of novel MTM analogues that selectively target EWS-FLI1 or other oncogenic transcription factors, as anti-cancer therapeutics. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  9. Likelihood-Based Confidence Intervals in Exploratory Factor Analysis

    Science.gov (United States)

    Oort, Frans J.

    2011-01-01

    In exploratory or unrestricted factor analysis, all factor loadings are free to be estimated. In oblique solutions, the correlations between common factors are free to be estimated as well. The purpose of this article is to show how likelihood-based confidence intervals can be obtained for rotated factor loadings and factor correlations, by…

  10. MOOC Success Factors: Proposal of an Analysis Framework

    Directory of Open Access Journals (Sweden)

    Margarida M. Marques

    2017-10-01

    Full Text Available Aim/Purpose: From an idea of lifelong-learning-for-all to a phenomenon affecting higher education, Massive Open Online Courses (MOOCs can be the next step to a truly universal education. Indeed, MOOC enrolment rates can be astoundingly high; still, their completion rates are frequently disappointingly low. Nevertheless, as courses, the participants’ enrolment and learning within the MOOCs must be considered when assessing their success. In this paper, the authors’ aim is to reflect on what makes a MOOC successful to propose an analysis framework of MOOC success factors. Background: A literature review was conducted to identify reported MOOC success factors and to propose an analysis framework. Methodology: This literature-based framework was tested against data of a specific MOOC and refined, within a qualitative interpretivist methodology. The data were collected from the ‘As alterações climáticas nos média escolares - Clima@EduMedia’ course, which was developed by the project Clima@EduMedia and was submitted to content analysis. This MOOC aimed to support science and school media teachers in the use of media to teach climate change Contribution: By proposing a MOOC success factors framework the authors are attempting to contribute to fill in a literature gap regarding what concerns criteria to consider a specific MOOC successful. Findings: This work major finding is a literature-based and empirically-refined MOOC success factors analysis framework. Recommendations for Practitioners: The proposed framework is also a set of best practices relevant to MOOC developers, particularly when targeting teachers as potential participants. Recommendation for Researchers: This work’s relevance is also based on its contribution to increasing empirical research on MOOCs. Impact on Society: By providing a proposal of a framework on factors to make a MOOC successful, the authors hope to contribute to the quality of MOOCs. Future Research: Future

  11. An intracellular targeted antibody detects EGFR as an independent prognostic factor in ovarian carcinomas

    International Nuclear Information System (INIS)

    Noske, Aurelia; Denkert, Carsten; Schwabe, Michael; Weichert, Wilko; Darb-Esfahani, Silvia; Buckendahl, Ann-Christin; Sehouli, Jalid; Braicu, Elena I; Budczies, Jan; Dietel, Manfred

    2011-01-01

    In ovarian cancer, the reported rate of EGFR expression varies between 4-70% depending on assessment method and data on patient outcome are conflicting. Methods: In this study we investigated EGFR expression and its prognostic value in a cohort of 121 invasive ovarian carcinomas, using a novel antibody against the intracellular domain of the receptor. We further evaluated an association between EGFR, the nuclear transporter CRM1 as well as COX-2. Furthermore, we evaluated EGFR expression in ten ovarian cancer cell lines and incubated cancer cells with Leptomycin B, a CRM1 specific inhibitor. We observed a membranous and cytoplasmic EGFR expression in 36.4% and 64% of ovarian carcinomas, respectively. Membranous EGFR was an independent prognostic factor for poor overall survival in ovarian cancer patients (HR 2.7, CI 1.1-6.4, p = 0.02) which was also found in the serous subtype (HR 4.6, CI 1.6-13.4, p = 0.004). We further observed a significant association of EGFR with COX-2 and nuclear CRM1 expression (chi-square test for trends, p = 0.006 and p = 0.013, respectively). In addition, combined membranous EGFR/COX-2 expression was significantly related to unfavorable overall survival (HR 7.2, CI 2.3-22.1, p = 0.001). In cell culture, we observed a suppression of EGFR protein levels after exposure to Leptomycin B in OVCAR-3 and SKOV-3 cells. Our results suggest that the EGFR/COX-2/CRM1 interaction might be involved in progression of ovarian cancer and patient prognosis. Hence, it is an interesting anti-cancer target for a combination therapy. Further studies will also be needed to investigate whether EGFR is also predictive for benefit from EGFR targeted therapies

  12. The epidermal growth factor receptor as a target for gastrointestinal cancer therapy.

    Science.gov (United States)

    Tedesco, Karen L; Lockhart, A Craig; Berlin, Jordan D

    2004-10-01

    The epidermal growth factor receptor (EGFR) is a member of the family of transmembrane protein kinase receptors known as the erbB or HER receptor family. When activated, EGFR phosphorylates and activates other intracellular proteins that affect cell signaling pathways, cellular proliferation, control of apoptosis and angiogenesis. EGFR signaling is best thought of as a network of activating and inactivating proteins with EGFR as the entry point into the network. EGFR overexpression occurs in most GI malignancies and while data are not entirely consistent, EGFR overexpression often confers a poor prognosis in those GI malignancies that have been studied. It often correlates with poorly differentiated histology, more advanced stage and other known poor prognostic markers. The EGFR is a tempting target because of its presence and overexpression on so many tumor types. However, downstream of the EGFR are several proteins that may be activated without EGFR thus allowing blockade to be overcome. Therefore, while blocking the activity of the EGFR protein appears to be a promising anticancer strategy, a simplistic strategy of blocking only EGFR is likely to only impact a minority of patients. It is time for the laboratory and clinical researchers to work closely together to develop this treatment strategy, moving back and forth from clinical to laboratory to best understand how to block this network effectively enough to produce a broader antitumor effect. While multiple methods of targeting the EGFR pathway are under development, including the inhibition of downstream proteins, only two modalities have entered clinical trials in GI malignancies: small molecule inhibitors of the intracellular kinase domain of EGFR and antibodies designed to block the extracellular ligand-binding domain of EGFR. EGFR inhibitors are still experimental in every GI malignancy with the notable exception of cetuximab that is approved for second or third-line therapy of metastatic colorectal

  13. Small interference RNA targeting tissue factor inhibits human lung adenocarcinoma growth in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Wang Jianing

    2011-05-01

    Full Text Available Abstract Background The human coagulation trigger tissue factor (TF is overexpressed in several types of cancer and involved in tumor growth, vascularization, and metastasis. To explore the role of TF in biological processes of lung adenocarcinoma, we used RNA interference (RNAi technology to silence TF in a lung adenocarcinoma cell line A549 with high-level expression of TF and evaluate its antitumor effects in vitro and in vivo. Methods The specific small interfering RNA (siRNA designed for targeting human TF was transfected into A549 cells. The expression of TF was detected by reverse transcription-PCR and Western blot. Cell proliferation was measured by MTT and clonogenic assays. Cell apoptosis was assessed by flow cytometry. The metastatic potential of A549 cells was determined by wound healing, the mobility and Matrigel invasion assays. Expressions of PI3K/Akt, Erk1/2, VEGF and MMP-2/-9 in transfected cells were detected by Western blot. In vivo, the effect of TF-siRNA on the growth of A549 lung adenocarcinoma xenografts in nude mice was investigated. Results TF -siRNA significantly reduced the expression of TF in the mRNA and protein levels. The down-regulation of TF in A549 cells resulted in the suppression of cell proliferation, invasion and metastasis and induced cell apoptosis in dose-dependent manner. Erk MAPK, PI3K/Akt pathways as well as VEGF and MMP-2/-9 expressions were inhibited in TF-siRNA transfected cells. Moreover, intratumoral injection of siRNA targeting TF suppressed the tumor growth of A549 cells in vivo model of lung adenocarcinoma. Conclusions Down-regulation of TF using siRNA could provide a potential approach for gene therapy against lung adenocarcinoma, and the antitumor effects may be associated with inhibition of Erk MAPK, PI3K/Akt pathways.

  14. Microphthalmia-associated transcription factor as the molecular target of cadmium toxicity in human melanocytes

    Energy Technology Data Exchange (ETDEWEB)

    Chantarawong, Wipa [Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Sendai (Japan); Inter Departmental Multidisciplinary Graduate Program in Bioscience, Faculty of Science, Kasetsart University, Bangkok (Thailand); Takeda, Kazuhisa; Sangartit, Weerapon; Yoshizawa, Miki [Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Sendai (Japan); Pradermwong, Kantimanee [Department of Zoology, Faculty of Science, Kasetsart University, Bangkok (Thailand); Shibahara, Shigeki, E-mail: shibahar@med.tohoku.ac.jp [Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Sendai (Japan)

    2014-11-28

    Highlights: • In human melanocytes, cadmium decreases the expression of MITF-M and tyrosinase and their mRNAs. • In human melanoma cells, cadmium decreases the expression of MITF-M protein and tyrosinase mRNA. • Expression of MITF-H is less sensitive to cadmium toxicity in melanocyte-linage cells. • Cadmium does not decrease the expression of MITF-H in retinal pigment epithelial cells. • MITF-M is the molecular target of cadmium toxicity in melanocytes. - Abstract: Dietary intake of cadmium is inevitable, causing age-related increase in cadmium accumulation in many organs, including hair, choroid and retinal pigment epithelium (RPE). Cadmium has been implicated in the pathogenesis of hearing loss and macular degeneration. The functions of cochlea and retina are maintained by melanocytes and RPE, respectively, and the differentiation of these pigment cells is regulated by microphthalmia-associated transcription factor (MITF). In the present study, we explored the potential toxicity of cadmium in the cochlea and retina by using cultured human melanocytes and human RPE cell lines. MITF consists of multiple isoforms, including melanocyte-specific MITF-M and widely expressed MITF-H. Levels of MITF-M protein and its mRNA in human epidermal melanocytes and HMV-II melanoma cells were decreased significantly by cadmium. In parallel with the MITF reduction, mRNA levels of tyrosinase, the key enzyme of melanin biosynthesis that is regulated by MITF-M, were also decreased. In RPE cells, however, the levels of total MITF protein, constituting mainly MITF-H, were not decreased by cadmium. We thus identify MITF-M as the molecular target of cadmium toxicity in melanocytes, thereby accounting for the increased risk of disability from melanocyte malfunction, such as hearing and vision loss among people with elevated cadmium exposure.

  15. Microphthalmia-associated transcription factor as the molecular target of cadmium toxicity in human melanocytes

    International Nuclear Information System (INIS)

    Chantarawong, Wipa; Takeda, Kazuhisa; Sangartit, Weerapon; Yoshizawa, Miki; Pradermwong, Kantimanee; Shibahara, Shigeki

    2014-01-01

    Highlights: • In human melanocytes, cadmium decreases the expression of MITF-M and tyrosinase and their mRNAs. • In human melanoma cells, cadmium decreases the expression of MITF-M protein and tyrosinase mRNA. • Expression of MITF-H is less sensitive to cadmium toxicity in melanocyte-linage cells. • Cadmium does not decrease the expression of MITF-H in retinal pigment epithelial cells. • MITF-M is the molecular target of cadmium toxicity in melanocytes. - Abstract: Dietary intake of cadmium is inevitable, causing age-related increase in cadmium accumulation in many organs, including hair, choroid and retinal pigment epithelium (RPE). Cadmium has been implicated in the pathogenesis of hearing loss and macular degeneration. The functions of cochlea and retina are maintained by melanocytes and RPE, respectively, and the differentiation of these pigment cells is regulated by microphthalmia-associated transcription factor (MITF). In the present study, we explored the potential toxicity of cadmium in the cochlea and retina by using cultured human melanocytes and human RPE cell lines. MITF consists of multiple isoforms, including melanocyte-specific MITF-M and widely expressed MITF-H. Levels of MITF-M protein and its mRNA in human epidermal melanocytes and HMV-II melanoma cells were decreased significantly by cadmium. In parallel with the MITF reduction, mRNA levels of tyrosinase, the key enzyme of melanin biosynthesis that is regulated by MITF-M, were also decreased. In RPE cells, however, the levels of total MITF protein, constituting mainly MITF-H, were not decreased by cadmium. We thus identify MITF-M as the molecular target of cadmium toxicity in melanocytes, thereby accounting for the increased risk of disability from melanocyte malfunction, such as hearing and vision loss among people with elevated cadmium exposure

  16. MicroRNA-214 suppresses gluconeogenesis by targeting activating transcriptional factor 4.

    Science.gov (United States)

    Li, Kai; Zhang, Jin; Yu, Junjie; Liu, Bin; Guo, Yajie; Deng, Jiali; Chen, Shanghai; Wang, Chunxia; Guo, Feifan

    2015-03-27

    Although the gluconeogenesis pathway is already a target for the treatment of type 2 diabetes, the potential role of microRNAs (miRNAs) in gluconeogenesis remains unclear. Here, we investigated the physiological functions of miR-214 in gluconeogenesis. The expression of miR-214 was suppressed by glucagon via protein kinase A signaling in primary hepatocytes, and miR-214 was down-regulated in the livers of fasted, high fat diet-induced diabetic and leptin receptor-mutated (db/db) mice. The overexpression of miR-214 in primary hepatocytes suppressed glucose production, and silencing miR-214 reversed this effect. Gluconeogenesis was suppressed in the livers of mice injected with an adenovirus expressing miR-214 (Ad-miR-214). Additionally, Ad-miR-214 alleviated high fat diet-induced elevation of gluconeogenesis and hyperglycemia. Furthermore, we found that activating transcription factor 4 (ATF4), a reported target of miR-214, can reverse the suppressive effect of miR-214 on gluconeogenesis in primary hepatocytes, and this suppressive effect was blocked in liver-specific ATF4 knock-out mice. ATF4 regulated gluconeogenesis via affecting forkhead box protein O1 (FOXO1) transcriptional activity. Finally, liver-specific miR-214 transgenic mice exhibited suppressed gluconeogenesis and reduced expression of ATF4, phosphoenolpyruvate carboxykinase, and glucose-6-phosphatase in liver. Taken together, our results suggest that the miR-214-ATF4 axis is a novel pathway for the regulation of hepatic gluconeogenesis. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. MicroRNA-214 Suppresses Gluconeogenesis by Targeting Activating Transcriptional Factor 4*

    Science.gov (United States)

    Li, Kai; Zhang, Jin; Yu, Junjie; Liu, Bin; Guo, Yajie; Deng, Jiali; Chen, Shanghai; Wang, Chunxia; Guo, Feifan

    2015-01-01

    Although the gluconeogenesis pathway is already a target for the treatment of type 2 diabetes, the potential role of microRNAs (miRNAs) in gluconeogenesis remains unclear. Here, we investigated the physiological functions of miR-214 in gluconeogenesis. The expression of miR-214 was suppressed by glucagon via protein kinase A signaling in primary hepatocytes, and miR-214 was down-regulated in the livers of fasted, high fat diet-induced diabetic and leptin receptor-mutated (db/db) mice. The overexpression of miR-214 in primary hepatocytes suppressed glucose production, and silencing miR-214 reversed this effect. Gluconeogenesis was suppressed in the livers of mice injected with an adenovirus expressing miR-214 (Ad-miR-214). Additionally, Ad-miR-214 alleviated high fat diet-induced elevation of gluconeogenesis and hyperglycemia. Furthermore, we found that activating transcription factor 4 (ATF4), a reported target of miR-214, can reverse the suppressive effect of miR-214 on gluconeogenesis in primary hepatocytes, and this suppressive effect was blocked in liver-specific ATF4 knock-out mice. ATF4 regulated gluconeogenesis via affecting forkhead box protein O1 (FOXO1) transcriptional activity. Finally, liver-specific miR-214 transgenic mice exhibited suppressed gluconeogenesis and reduced expression of ATF4, phosphoenolpyruvate carboxykinase, and glucose-6-phosphatase in liver. Taken together, our results suggest that the miR-214-ATF4 axis is a novel pathway for the regulation of hepatic gluconeogenesis. PMID:25657009

  18. Erikson Psychosocial Stage Inventory: A Factor Analysis

    Science.gov (United States)

    Gray, Mary McPhail; And Others

    1986-01-01

    The 72-item Erikson Psychosocial Stage Inventory (EPSI) was factor analyzed for a group of 534 university freshmen and sophomore students. Seven factors emerged, which were labeled Initiative, Industry, Identity, Friendship, Dating, Goal Clarity, and Self-Confidence. Item's representing Erikson's factors, Trust and Autonomy, were dispersed across…

  19. Housing price forecastability: A factor analysis

    DEFF Research Database (Denmark)

    Bork, Lasse; Møller, Stig Vinther

    of the model stays high at longer horizons. The estimated factors are strongly statistically signi…cant according to a bootstrap resampling method which takes into account that the factors are estimated regressors. The simple three-factor model also contains substantial out-of-sample predictive power...

  20. MicroRNA-195 induced apoptosis in hypoxic chondrocytes by targeting hypoxia-inducible factor 1 alpha.

    Science.gov (United States)

    Bai, R; Zhao, A-Q; Zhao, Z-Q; Liu, W-L; Jian, D-M

    2015-02-01

    The chondrocytes, the resident cells of cartilage, are maintained and take effects in the whole life upon chronic hypoxic exposure, which hypoxia-inducible factor 1 alpha (HIF-1α) play pivotal roles in response to. Dysregulation of some microRNA (miRNAs) have also been identified to be involved in hypoxia-related physiologic and pathophysiologic responses in some tissues or cell lines. However, the mechanism of miRNAs reponse to hypoxia remain largely unknown in chondrocytes, including the microRNA-195 (miR-195). AIM To investigate the effects of microRNAs (miRNAs) and hypoxia-inducible factor 1 alpha (HIF-1α) on chondrocytes in physiologic environment. We compared the expression of miR-195 and HIF-1α mRNA on hypoxia with that on normoxia in ATDC 5 cells by qRT-PCR. Further experiments was performed to confirmed the relationships of miR-195 and HIF-1α by bioinformatics analysis and dual reporter gene assay. we also assessed the effect of miR-195 on apoptosis in hypoxic ATDC 5 cells by transfect with miR-195 mimics. It was found the downregulated miR-195 and upregulated HIF-1α were present in hypoxic ATDC 5 cells. miR-195 negatively regulated HIF-1α by targeting its 3'-untranslated region. Moreover, the founding indicated miR-195 greatly increased apoptosis and downregulated HIF-1α mRNA occurred simultaneously in hypoxic chondrocytes. We concluded that miR-195 induced apoptosis in hypoxic chondrocytes by directly targeting HIF-1α.

  1. Targeting factor VIII expression to platelets for hemophilia A gene therapy does not induce an apparent thrombotic risk in mice.

    Science.gov (United States)

    Baumgartner, C K; Mattson, J G; Weiler, H; Shi, Q; Montgomery, R R

    2017-01-01

    Essentials Platelet-Factor (F) VIII gene therapy is a promising treatment in hemophilia A. This study aims to evaluate if platelet-FVIII expression would increase the risk for thrombosis. Targeting FVIII expression to platelets does not induce or elevate thrombosis risk. Platelets expressing FVIII are neither hyper-activated nor hyper-responsive. Background Targeting factor (F) VIII expression to platelets is a promising gene therapy approach for hemophilia A, and is successful even in the presence of inhibitors. It is well known that platelets play important roles not only in hemostasis, but also in thrombosis and inflammation. Objective To evaluate whether platelet-FVIII expression might increase thrombotic risk and thereby compromise the safety of this approach. Methods In this study, platelet-FVIII-expressing transgenic mice were examined either in steady-state conditions or under prothrombotic conditions induced by inflammation or the FV Leiden mutation. Native whole blood thrombin generation assay, rotational thromboelastometry analysis and ferric chloride-induced vessel injury were used to evaluate the hemostatic properties. Various parameters associated with thrombosis risk, including D-dimer, thrombin-antithrombin complexes, fibrinogen, tissue fibrin deposition, platelet activation status and activatability, and platelet-leukocyte aggregates, were assessed. Results We generated a new line of transgenic mice that expressed 30-fold higher levels of platelet-expressed FVIII than are therapeutically required to restore hemostasis in hemophilic mice. Under both steady-state conditions and prothrombotic conditions induced by lipopolysaccharide-mediated inflammation or the FV Leiden mutation, supratherapeutic levels of platelet-expressed FVIII did not appear to be thrombogenic. Furthermore, FVIII-expressing platelets were neither hyperactivated nor hyperactivatable upon agonist activation. Conclusion We conclude that, in mice, more than 30-fold higher levels of

  2. Alternative Factor Models and Factorial Invariance of the GHQ-12: A Large Sample Analysis Using Confirmatory Factor Analysis

    Science.gov (United States)

    Shevlin, Mark; Adamson, Gary

    2005-01-01

    This study tested alternative factor models of the General Health Questionnaire-12 (GHQ-12), based on previous research findings, with a large sample using confirmatory factor analysis. An alternative models framework was used to test 6 factor analytic models. A 3-factor model was the best explanation of the sample data. The 3 factors were labeled…

  3. Evaluation in medical education: A topical review of target parameters, data collection tools and confounding factors

    Directory of Open Access Journals (Sweden)

    Schiekirka, Sarah

    2015-09-01

    Full Text Available Background and objective: Evaluation is an integral part of education in German medical schools. According to the quality standards set by the German Society for Evaluation, evaluation tools must provide an accurate and fair appraisal of teaching quality. Thus, data collection tools must be highly reliable and valid. This review summarises the current literature on evaluation of medical education with regard to the possible dimensions of teaching quality, the psychometric properties of survey instruments and potential confounding factors.Methods: We searched Pubmed, PsycINFO and PSYNDEX for literature on evaluation in medical education and included studies published up until June 30, 2011 as well as articles identified in the “grey literature”. Results are presented as a narrative review.Results: We identified four dimensions of teaching quality: structure, process, teacher characteristics, and outcome. Student ratings are predominantly used to address the first three dimensions, and a number of reliable tools are available for this purpose. However, potential confounders of student ratings pose a threat to the validity of these instruments. Outcome is usually operationalised in terms of student performance on examinations, but methodological problems may limit the usability of these data for evaluation purposes. In addition, not all examinations at German medical schools meet current quality standards.Conclusion: The choice of tools for evaluating medical education should be guided by the dimension that is targeted by the evaluation. Likewise, evaluation results can only be interpreted within the context of the construct addressed by the data collection tool that was used as well as its specific confounding factors.

  4. Prevalence and risk factors for central diabetes insipidus in cardiac arrest survivor treated with targeted temperature management.

    Science.gov (United States)

    Lee, Dong Hun; Lee, Byung Kook; Song, Kyoung Hwan; Jung, Yong Hun; Park, Jung Soo; Lee, Sung Min; Cho, Yong Soo; Kim, Jin Woong; Jeung, Kyung Woon

    2016-08-01

    Central diabetes insipidus (CDI) is a marker of severe brain injury. Here we aimed to investigate the prevalence and risk factors of CDI in cardiac arrest survivors treated with targeted temperature management (TTM). This retrospective observational study included consecutive adult cardiac arrest survivors treated with TTM between 2008 and 2014. Central diabetes insipidus was confirmed if all of the following criteria were met: urine volume >50 cc kg(-1) d(-1), serum osmolarity >300 mmol/L, urine osmolarity 145 mEq/L. The primary outcome was the incidence of CDI. Of the 385 included patients, 45 (11.7%) had confirmed central CDI. Univariate analysis showed that younger age, nonwitness of collapse, nonshockable rhythm, a high incidence of asphyxia arrest, longer downtime, and lower initial core temperature were associated with CDI development. Patients with CDI had a higher incidence of poor neurologic outcomes at discharge and higher in-hospital mortality rate (20/45 vs 76/340, P= .001) as well as 180-day mortality (44/45 vs 174/340, Pdiabetes insipidus developed in 12% of cardiac arrest survivors treated with TTM, and those with CDI showed poor neurologic outcomes and high mortality rates. Younger age, nonshockable rhythm, long downtime, and asphyxia arrest were significant risk factors for development of CDI. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Current target industry analysis: Las Vegas Metropolitan Area

    International Nuclear Information System (INIS)

    Boyle, M.R.

    1988-06-01

    This is the second of three reports dealing with the Las Vegas MSA's economic development potential in support of an overall effort to prepare an environmental impact statement for the proposed underground nuclear waste storage facility at Yucca Mountain. The first report provides an assessment of the MSA current business climate for economic growth. This second report draws on that business climate assessment to evaluate the Las Vegas MSA's competitive posture in pursuing business investment in the ''primary'' sector of the economy -- businesses which sell their products or services outside the local marketplace and bring new money back into the area and businesses serving local customers who would otherwise import these products or services from suppliers outside the area. GSO has developed an analytic tool which attempts to model the decision process used by businesses in selecting locations for new or expanded business investment. This computer based model reflects variations in site selection decision making among industries and ownership and management types. The underlying premise of the GSO locational compatibility index (LCI) model is that locational decisions are based more on a process of elimination that on a process of selection. There are many factors, some essential and some desirable, which influence any site selection decision. Multivariate comparative analyses narrow the geographic field to a region, then a group of states, then a state, then a sub-state region, then a community and finally to a specific site. Sometimes these analyses are rational and quantitative. More often, they are at least partially random and intuitive. 2 tabs

  6. Nominal Performance Biosphere Dose Conversion Factor Analysis

    Energy Technology Data Exchange (ETDEWEB)

    M. Wasiolek

    2000-12-21

    The purpose of this report was to document the process leading to development of the Biosphere Dose Conversion Factors (BDCFs) for the postclosure nominal performance of the potential repository at Yucca Mountain. BDCF calculations concerned twenty-four radionuclides. This selection included sixteen radionuclides that may be significant nominal performance dose contributors during the compliance period of up to 10,000 years, five additional radionuclides of importance for up to 1 million years postclosure, and three relatively short-lived radionuclides important for the human intrusion scenario. Consideration of radionuclide buildup in soil caused by previous irrigation with contaminated groundwater was taken into account in the BDCF development. The effect of climate evolution, from the current arid conditions to a wetter and cooler climate, on the BDCF values was evaluated. The analysis included consideration of different exposure pathway's contribution to the BDCFs. Calculations of nominal performance BDCFs used the GENII-S computer code in a series of probabilistic realizations to propagate the uncertainties of input parameters into the output. BDCFs for the nominal performance, when combined with the concentrations of radionuclides in groundwater allow calculation of potential radiation doses to the receptor of interest. Calculated estimates of radionuclide concentration in groundwater result from the saturated zone modeling. The integration of the biosphere modeling results (BDCFs) with the outcomes of the other component models is accomplished in the Total System Performance Assessment (TSPA) to calculate doses to the receptor of interest from radionuclides postulated to be released to the environment from the potential repository at Yucca Mountain.

  7. Disruptive Event Biosphere Doser Conversion Factor Analysis

    Energy Technology Data Exchange (ETDEWEB)

    M. Wasiolek

    2000-12-28

    The purpose of this report was to document the process leading to, and the results of, development of radionuclide-, exposure scenario-, and ash thickness-specific Biosphere Dose Conversion Factors (BDCFs) for the postulated postclosure extrusive igneous event (volcanic eruption) at Yucca Mountain. BDCF calculations were done for seventeen radionuclides. The selection of radionuclides included those that may be significant dose contributors during the compliance period of up to 10,000 years, as well as radionuclides of importance for up to 1 million years postclosure. The approach documented in this report takes into account human exposure during three different phases at the time of, and after, volcanic eruption. Calculations of disruptive event BDCFs used the GENII-S computer code in a series of probabilistic realizations to propagate the uncertainties of input parameters into the output. The pathway analysis included consideration of different exposure pathway's contribution to the BDCFs. BDCFs for volcanic eruption, when combined with the concentration of radioactivity deposited by eruption on the soil surface, allow calculation of potential radiation doses to the receptor of interest. Calculation of radioactivity deposition is outside the scope of this report and so is the transport of contaminated ash from the volcano to the location of the receptor. The integration of the biosphere modeling results (BDCFs) with the outcomes of the other component models is accomplished in the Total System Performance Assessment (TSPA), in which doses are calculated to the receptor of interest from radionuclides postulated to be released to the environment from the potential repository at Yucca Mountain.

  8. Nominal Performance Biosphere Dose Conversion Factor Analysis

    International Nuclear Information System (INIS)

    Wasiolek, M.

    2000-01-01

    The purpose of this report was to document the process leading to development of the Biosphere Dose Conversion Factors (BDCFs) for the postclosure nominal performance of the potential repository at Yucca Mountain. BDCF calculations concerned twenty-four radionuclides. This selection included sixteen radionuclides that may be significant nominal performance dose contributors during the compliance period of up to 10,000 years, five additional radionuclides of importance for up to 1 million years postclosure, and three relatively short-lived radionuclides important for the human intrusion scenario. Consideration of radionuclide buildup in soil caused by previous irrigation with contaminated groundwater was taken into account in the BDCF development. The effect of climate evolution, from the current arid conditions to a wetter and cooler climate, on the BDCF values was evaluated. The analysis included consideration of different exposure pathway's contribution to the BDCFs. Calculations of nominal performance BDCFs used the GENII-S computer code in a series of probabilistic realizations to propagate the uncertainties of input parameters into the output. BDCFs for the nominal performance, when combined with the concentrations of radionuclides in groundwater allow calculation of potential radiation doses to the receptor of interest. Calculated estimates of radionuclide concentration in groundwater result from the saturated zone modeling. The integration of the biosphere modeling results (BDCFs) with the outcomes of the other component models is accomplished in the Total System Performance Assessment (TSPA) to calculate doses to the receptor of interest from radionuclides postulated to be released to the environment from the potential repository at Yucca Mountain

  9. Target detection in SAR images via radiometric multi-resolution analysis

    Science.gov (United States)

    Hu, Jingwen; Xia, Gui-Song; Sun, Hong

    2013-10-01

    This paper presents a target detection method in synthetic aperture radar (SAR) images with radiometric multiresolution analysis (RMA). The idea is that target saliency can be efficiently computed by comparing the statistics of targets and those of the local background around them. In order to compute reliable statistics of targets, which usually involve a small number of pixels, RMA is adopted. The RMA preprocessing method performs well in stabilizing the statistical characteristics of SAR images. It can effectively restrain the speckle noise while keep the statistical characteristics of the original image. Based on the computed target saliency, adaptive decision thresholds are got by using the constant false alarm rate (CFAR) target detection framework. Our experiments on real SAR images show that the proposed method can achieve better performance compared with the traditional cell average-constant false alarm rate (CA-CFAR) method.

  10. Beyond typing and grading: target analysis in individualized therapy as a new challenge for tumour pathology.

    Science.gov (United States)

    Kreipe, Hans H; von Wasielewski, Reinhard

    2007-01-01

    In order to bring about its beneficial effects in oncology, targeted therapy depends on accurate target analysis. Whether cells of a tumour will be sensitive to a specific treatment is predicted by the detection of appropriate targets in cancer tissue by immunohistochemistry or molecular methods. In most instances this is performed by histopathologists. Reliability and reproducibility of tissue-based target analysis in histopathology require novel measures of quality assurance by internal and external controls. As a model for external quality assurance in targeted therapy an annual inter-laboratory trial has been set up in Germany applying tissue arrays with up to 60 mammary cancer samples which are tested by participants for expression of HER2/neu and steroid hormone receptors.

  11. Functional analysis of jasmonate-responsive transcription factors in Arabidopsis thaliana

    NARCIS (Netherlands)

    Zarei, Adel

    2007-01-01

    The aim of the studies described in this thesis was the functional analysis of JA-responsive transcription factors in Arabidopsis with an emphasis on the interaction with the promoters of their target genes. In short, the following new results were obtained. The promoter of the PDF1.2 gene contains

  12. Cell physiology regulation by hypoxia inducible factor-1: Targeting oxygen-related nanomachineries of hypoxic cells.

    Science.gov (United States)

    Eskandani, Morteza; Vandghanooni, Somayeh; Barar, Jaleh; Nazemiyeh, Hossein; Omidi, Yadollah

    2017-06-01

    Any dysfunctionality in maintaining the oxygen homeostasis by mammalian cells may elicit hypoxia/anoxia, which results in inescapable oxidative stress and possible subsequent detrimental impacts on certain cells/tissues with high demands to oxygen molecules. The ischemic damage in turn can trigger initiation of a number of diseases including organs ischemia, metabolic disorders, inflammatory diseases, different types of malignancies, and alteration in wound healing process. Thus, full comprehension of molecular mechanism(s) and cellular physiology of the oxygen homeostasis is the cornerstone of the mammalian cells metabolism, energetic pathways and health and disease conditions. An imbalance in oxygen content within the cellular microenvironment activates a cascade of molecular events that are often compensated, otherwise pathologic condition occurs through a complexed network of biomolecules. Hypoxia inducible factor-1 (HIF-1) plays a key transcriptional role in the adaptation of cell physiology in relation with the oxygen content within a cell. In this current study, we provide a comprehensive review on the molecular mechanisms of oxygen sensing and homeostasis and the impacts of HIF-1 in hypoxic/anoxic conditions. Moreover, different molecular and biochemical responses of the cells to the surrounding environment are discussed in details. Finally, modern technological approaches for targeting the hypoxia related proteins are articulated. Copyright © 2017. Published by Elsevier B.V.

  13. Radiolabeled Probes Targeting Hypoxia-Inducible Factor-1-Active Tumor Microenvironments

    Directory of Open Access Journals (Sweden)

    Masashi Ueda

    2014-01-01

    Full Text Available Because tumor cells grow rapidly and randomly, hypoxic regions arise from the lack of oxygen supply in solid tumors. Hypoxic regions in tumors are known to be resistant to chemotherapy and radiotherapy. Hypoxia-inducible factor-1 (HIF-1 expressed in hypoxic regions regulates the expression of genes related to tumor growth, angiogenesis, metastasis, and therapy resistance. Thus, imaging of HIF-1-active regions in tumors is of great interest. HIF-1 activity is regulated by the expression and degradation of its α subunit (HIF-1α, which is degraded in the proteasome under normoxic conditions, but escapes degradation under hypoxic conditions, allowing it to activate transcription of HIF-1-target genes. Therefore, to image HIF-1-active regions, HIF-1-dependent reporter systems and injectable probes that are degraded in a manner similar to HIF-1α have been recently developed and used in preclinical studies. However, no probe currently used in clinical practice directly assesses HIF-1 activity. Whether the accumulation of 18F-FDG or 18F-FMISO can be utilized as an index of HIF-1 activity has been investigated in clinical studies. In this review, the current status of HIF-1 imaging in preclinical and clinical studies is discussed.

  14. Diacetoxyscirpenol as a new anticancer agent to target hypoxia-inducible factor 1

    Science.gov (United States)

    Choi, Yong-Joon; Shin, Hyun-Woo; Chun, Yang-Sook; Leutou, Alain Simplice; Son, Byeng Wha; Park, Jong-Wan

    2016-01-01

    Hypoxia activates hypoxia-inducible factor 1, which promotes the progression of malignancy by stimulating angiogenesis and by augmenting the ability of tumors to survive. Thus, HIF-1 is one of the most compelling targets for treating cancers. The aim of this study was to find a small molecule that inhibits HIF-1 under hypoxia in cancer cells. 7,280 compounds in a chemical library were tested in a cancer cell line expressing luciferase HIF-dependently. Through three rounds of screening, we finally picked up a compound that originates from a marine bacterium parasitizing red alga. The antibiotic potently inhibited HIF-1 expression and its transcriptional activity in cancer cells exposed to hypoxia. Through two-step fractionation, diacetoxyscirpenol was purified and identified as a HIF-inhibiting ingredient. Mechanistically, diacetoxyscirpenol inhibits the synthesis of HIF-1α protein and also interferes with the dimerization of HIF-1α and ARNT. It attenuates HIF-mediated gene expression in cancer cells exposed to hypoxia, and by doing so reduces tumorigenic and angiogenic potentials of cancer cells. More importantly, diacetoxyscirpenol retarded tumor growth in mice, and reduced HIF-1α expression and vascular formation in the tumors. Overall, diacetoxyscirpenol is considered a potential drug deregulating the HIF-1 signaling pathway, and it could be beneficially employed for treating malignant tumors with hypoxic microenvironment. PMID:27613833

  15. Platelet-activating factor (PAF) receptor as a promising target for cancer cell repopulation after radiotherapy

    Science.gov (United States)

    da Silva-Jr, I A; Chammas, R; Lepique, A P; Jancar, S

    2017-01-01

    A major drawback of radiotherapy is the accelerated growth of the surviving tumor cells. Radiotherapy generates a variety of lipids that bind to the receptor for platelet-activating factor, expressed by cells in the tumor microenvironment. In the present study, using the TC-1 tumor cell line, we found that irradiation induced a twofold increase in receptor expression and generated agonists of receptor. Irradiated cells induced a 20-fold increase in live TC-1 proliferation in vitro. Furthermore, subcutaneous co-injection of irradiated TC-1 cells with TC-1 expressing luciferase (TC-1 fluc+) markedly increased TC-1 fluc+ proliferation in a receptor-dependent way. Moreover we used a human carcinoma cell line not expressing the PAF receptor (KBM) and the same cell transfected with the receptor gene (KBP). Following co-injection of live KBP cells with irradiated KBM in RAG mice, the tumor growth was significantly increased compared with tumor formed following co-injection of live KBM with irradiated KBM. This tumor cell repopulation correlated with increased infiltration of tumor-promoting macrophages (CD206+). We propose that receptor represents a possible target for improving the efficacy of radiotherapy through inhibition of tumor repopulation. PMID:28134937

  16. Orexin-corticotropin-releasing factor receptor heteromers in the ventral tegmental area as targets for cocaine.

    Science.gov (United States)

    Navarro, Gemma; Quiroz, César; Moreno-Delgado, David; Sierakowiak, Adam; McDowell, Kimberly; Moreno, Estefanía; Rea, William; Cai, Ning-Sheng; Aguinaga, David; Howell, Lesley A; Hausch, Felix; Cortés, Antonio; Mallol, Josefa; Casadó, Vicent; Lluís, Carme; Canela, Enric I; Ferré, Sergi; McCormick, Peter J

    2015-04-29

    Release of the neuropeptides corticotropin-releasing factor (CRF) and orexin-A in the ventral tegmental area (VTA) play an important role in stress-induced cocaine-seeking behavior. We provide evidence for pharmacologically significant interactions between CRF and orexin-A that depend on oligomerization of CRF1 receptor (CRF1R) and orexin OX1 receptors (OX1R). CRF1R-OX1R heteromers are the conduits of a negative crosstalk between orexin-A and CRF as demonstrated in transfected cells and rat VTA, in which they significantly modulate dendritic dopamine release. The cocaine target σ1 receptor (σ1R) also associates with the CRF1R-OX1R heteromer. Cocaine binding to the σ1R-CRF1R-OX1R complex promotes a long-term disruption of the orexin-A-CRF negative crosstalk. Through this mechanism, cocaine sensitizes VTA cells to the excitatory effects of both CRF and orexin-A, thus providing a mechanism by which stress induces cocaine seeking. Copyright © 2015 the authors 0270-6474/15/356639-15$15.00/0.

  17. Orexin–Corticotropin-Releasing Factor Receptor Heteromers in the Ventral Tegmental Area as Targets for Cocaine

    Science.gov (United States)

    Navarro, Gemma; Quiroz, César; Moreno-Delgado, David; Sierakowiak, Adam; McDowell, Kimberly; Moreno, Estefanía; Rea, William; Cai, Ning-Sheng; Aguinaga, David; Howell, Lesley A.; Hausch, Felix; Cortés, Antonio; Mallol, Josefa; Casadó, Vicent; Lluís, Carme; Canela, Enric I.

    2015-01-01

    Release of the neuropeptides corticotropin-releasing factor (CRF) and orexin-A in the ventral tegmental area (VTA) play an important role in stress-induced cocaine-seeking behavior. We provide evidence for pharmacologically significant interactions between CRF and orexin-A that depend on oligomerization of CRF1 receptor (CRF1R) and orexin OX1 receptors (OX1R). CRF1R–OX1R heteromers are the conduits of a negative crosstalk between orexin-A and CRF as demonstrated in transfected cells and rat VTA, in which they significantly modulate dendritic dopamine release. The cocaine target σ1 receptor (σ1R) also associates with the CRF1R–OX1R heteromer. Cocaine binding to the σ1R–CRF1R–OX1R complex promotes a long-term disruption of the orexin-A–CRF negative crosstalk. Through this mechanism, cocaine sensitizes VTA cells to the excitatory effects of both CRF and orexin-A, thus providing a mechanism by which stress induces cocaine seeking. PMID:25926444

  18. Circumvention of nuclear factor kappaB-induced chemoresistance by cytoplasmic-targeted anthracyclines.

    Science.gov (United States)

    Bilyeu, Jennifer D; Panta, Ganesh R; Cavin, Lakita G; Barrett, Christina M; Turner, Eddie J; Sweatman, Trevor W; Israel, Mervyn; Lothstein, Leonard; Arsura, Marcello

    2004-04-01

    Nuclear factor kappaB (NF-kappaB) has been implicated in inducible chemoresistance against anthracyclines. In an effort to improve the cytotoxicity of anthracyclines while reducing their cardiotoxic effects, we have developed a novel class of extranuclear-localizing 14-O-acylanthracyclines that bind to the phorbol ester/diacylglycerol-binding C1b domain of conventional and novel protein kinase C (PKC) isoforms, thereby promoting an apoptotic response. Because PKCs have been shown to be involved in NF-kappaB activation, in this report, we determined the mechanism of NF-kappaB activation by N-benzyladriamycin-14-valerate (AD 198) and N-benzyladriamycin-14-pivalate (AD 445), two novel 14-O-acylanthracylines. We show that the induction of NF-kappaB activity in response to drug treatment relies on the activation of PKC-delta and NF-kappaB-activating kinase (NAK), independent of ataxia telengectasia mutated and p53 activities. In turn, NAK activates the IKK complex through phosphorylation of the IKK-2 subunit. We find that neither NF-kappaB activation nor ectopic expression of Bcl-X(L) confers protection from AD 198-induced cell killing. Overall, our data indicate that activation of novel PKC isoforms by cytoplasmic-targeted 14-O-acylanthracyclines promotes an apoptotic response independent of DNA damage, which is unimpeded by inducible activation of NF-kappaB.

  19. Effects of a Workplace Intervention Targeting Psychosocial Risk Factors on Safety and Health Outcomes.

    Science.gov (United States)

    Hammer, Leslie B; Truxillo, Donald M; Bodner, Todd; Rineer, Jennifer; Pytlovany, Amy C; Richman, Amy

    2015-01-01

    The goal of this study was to test the effectiveness of a workplace intervention targeting work-life stress and safety-related psychosocial risk factors on health and safety outcomes. Data were collected over time using a randomized control trial design with 264 construction workers employed in an urban municipal department. The intervention involved family- and safety-supportive supervisor behavior training (computer-based), followed by two weeks of behavior tracking and a four-hour, facilitated team effectiveness session including supervisors and employees. A significant positive intervention effect was found for an objective measure of blood pressure at the 12-month follow-up. However, no significant intervention results were found for self-reported general health, safety participation, or safety compliance. These findings suggest that an intervention focused on supervisor support training and a team effectiveness process for planning and problem solving should be further refined and utilized in order to improve employee health with additional research on the beneficial effects on worker safety.

  20. Inhibition of fibroblasts reduced head and neck cancer growth by targeting fibroblast growth factor receptor.

    Science.gov (United States)

    Sweeny, Larissa; Liu, Zhiyong; Lancaster, William; Hart, Justin; Hartman, Yolanda E; Rosenthal, Eben L

    2012-07-01

    Head and neck squamous cell carcinoma (HNSCC) is a complex disease process involving interactions with carcinoma-associated fibroblasts and endothelial cells. We further investigated these relationships by suppressing stromal cell growth through the inhibition of fibroblast growth factor receptor (FGFR). Preclinical investigation. HNSCC cell lines (FADU, OSC19, Cal27, SCC1, SCC5, SCC22A), fibroblast (HS27), and endothelial cells (human umbilical vascular endothelial cell) were cultured individually or in coculture. Proliferation was assessed following treatment with a range of physiologic concentrations of FGFR inhibitor PD173074. Mice bearing established HNSCC xenografts were treated with PD173074 (12 mg/kg), and tumor histology was analyzed for stromal composition, proliferation (Ki67 staining), and apoptosis (TUNEL [terminal deoxynucleotidyl transferase dUTP nick end labeling] staining). In vitro, inhibition of FGFR with PD173074 dramatically reduced proliferation of fibroblasts and endothelial cells compared to untreated controls. However, HNSCC cell proliferation was not affected by inhibition of FGFR. When cocultured with fibroblasts, HNSCC cells proliferation increased by 15% to 80% (P fibroblast-enhanced tumor cell growth was suppressed by FGFR inhibition. Additionally, treatment of mice bearing HNSCC xenografts with PD173074 resulted in significant growth inhibition (P < .001). Additionally, those tumors from mice treated with PD173074 had a smaller stromal component, decreased proliferation, and increased apoptosis. Targeting the FGFR pathway in head and neck cancer acts through the stromal components to decrease HNSCC growth in vivo and in vitro. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

  1. Identification of the Drosophila Mes4 gene as a novel target of the transcription factor DREF

    Energy Technology Data Exchange (ETDEWEB)

    Suyari, Osamu; Ida, Hiroyuki [Department of Applied Biology, Kyoto Institute of Technology, Sakyo-ku, Kyoto 606-8585 (Japan); Insect Biomedical Research Center, Kyoto Institute of Technology, Sakyo-ku, Kyoto 606-8585 (Japan); Yoshioka, Yasuhide; Kato, Yasuko; Hashimoto, Reina [Department of Applied Biology, Kyoto Institute of Technology, Sakyo-ku, Kyoto 606-8585 (Japan); Insect Biomedical Research Center, Kyoto Institute of Technology, Sakyo-ku, Kyoto 606-8585 (Japan); Venture Laboratory, Kyoto Institute of Technology, Sakyo-ku, Kyoto 606-8585 (Japan); Yamaguchi, Masamitsu, E-mail: myamaguc@kit.ac.jp [Department of Applied Biology, Kyoto Institute of Technology, Sakyo-ku, Kyoto 606-8585 (Japan); Insect Biomedical Research Center, Kyoto Institute of Technology, Sakyo-ku, Kyoto 606-8585 (Japan)

    2009-05-01

    The Mes4 gene has been identified as one of the maternal Dorsal target genes in Drosophila. In the present study, we found a DNA replication-related element (DRE, 5'-TATCGATA) in the Mes4 promoter recognized by the DRE-binding factor (DREF). Luciferase transient expression assays in S2 cells using Mes4 promoter-luciferase fusion plasmids revealed that the DRE sequence is essential for Mes4 promoter activity. Requirement of DRE for Mes4 promoter activity was further confirmed by anti-{beta}-galactosidase antibody-staining of various tissues from transgenic flies carrying Mes4 promoter-lacZ fusion genes. Furthermore, wild type Mes4 promoter activity was decreased by 40% in DREF-depleted S2 cells. These results indicate that DREF positively regulates Mes4 gene expression. Band mobility shift analyses using Kc cell nuclear extracts further indicated that the DRE sequence in the Mes4 promoter is especially important for binding to DREF. Moreover, specific binding of DREF to the involved genomic region could be demonstrated by chromatin immunoprecipitation assays using anti-DREF antibodies. These results, taken together, indicate that the DRE/DREF system activates transcription of the Mes4 gene. In addition, knockdown of the Mes4 gene in wing imaginal discs using the GAL4-UAS system caused an atrophied wing phenotype, suggesting that Mes4 is required for wing morphogenesis.

  2. Targeting the centriolar replication factor STIL synergizes with DNA damaging agents for treatment of ovarian cancer

    Science.gov (United States)

    Rabinowicz, Noa; Mangala, Lingegowda S.; Brown, Kevin R.; Checa-Rodriguez, Cintia; Castiel, Asher; Moskovich, Oren; Zarfati, Giulia; Trakhtenbrot, Luba; Levy-Barda, Adva; Jiang, Dahai; Rodriguez-Aguayo, Cristian; Pradeep, Sunila; van Praag, Yael; Lopez-Berestein, Gabriel; David, Ahuvit; Novikov, Ilya; Huertas, Pablo; Rottapel, Robert; Sood, Anil K.; Izraeli, Shai

    2017-01-01

    Advanced ovarian cancer is an incurable disease. Thus, novel therapies are required. We wished to identify new therapeutic targets for ovarian cancer. ShRNA screen performed in 42 ovarian cancer cell lines identified the centriolar replication factor STIL as an essential gene for ovarian cancer cells. This was verified in-vivo in orthotopic human ovarian cancer mouse models. STIL depletion by administration of siRNA in neutral liposomes resulted in robust anti-tumor effect that was further enhanced in combination with cisplatin. Consistent with this finding, STIL depletion enhanced the extent of DNA double strand breaks caused by DNA damaging agents. This was associated with centrosomal depletion, ongoing genomic instability and enhanced formation of micronuclei. Interestingly, the ongoing DNA damage was not associated with reduced DNA repair. Indeed, we observed that depletion of STIL enhanced canonical homologous recombination repair and increased BRCA1 and RAD51 foci in response to DNA double strand breaks. Thus, inhibition of STIL significantly enhances the efficacy of DNA damaging chemotherapeutic drugs in treatment of ovarian cancer. PMID:28423708

  3. Analysis of drug adversiting targeted to health professionals

    Directory of Open Access Journals (Sweden)

    Marcela Campos Esqueff Abdalla

    2017-08-01

    Full Text Available The advertising of medicines is the dissemination of the product by the pharmaceutical industry, with emphasis on brand, aiming to promote their prescription and/or purchase. This practice must comply with the legal provisions in effect determined by Brazilian National Surveillance Agency. The present work aimed to analyze advertisements of medicines offered by the industry to health professionals. The capture of advertisements covered physician offices of various specialties, public and private hospitals and magazines directed at health professionals. The analysis of the collected parts involved the verification of legibility and viewing of information required, as well as the compliance with the health legislation that regulates the promotion and advertising of medicines in Brazil – agency’s resolution n. 96/2008. The results showed that no piece meets the health legislation in full. Most industries employs strategies that hinder access to restricted information of use of the medicine, as contra-indications, for example, constituting an obstacle to rational use. It was also observed the presence of indications other than those approved by the agency and use indication for different age groups in the specified product registration. It is obvious the need for a new model controller and more rigid regulator that prioritize above all particular interests, a major importance, that is the society. This must be protected from false advertising and abusive, promoting the rational use of medicines.

  4. Targeted resequencing and analysis of the Diamond-Blackfan anemia disease locus RPS19.

    Directory of Open Access Journals (Sweden)

    Alvaro Martinez Barrio

    2009-07-01

    Full Text Available The Ribosomal protein S19 gene locus (RPS19 has been linked to two kinds of red cell aplasia, Diamond-Blackfan Anemia (DBA and Transient Erythroblastopenia in Childhood (TEC. Mutations in RPS19 coding sequences have been found in 25% of DBA patients, but not in TEC patients. It has been suggested that non-coding RPS19 sequence variants contribute to the considerable clinical variability in red cell aplasia. We therefore aimed at identifying non-coding variations associated with DBA or TEC phenotypes.We targeted a region of 19'980 bp encompassing the RPS19 gene in a cohort of 89 DBA and TEC patients for resequencing. We provide here a catalog of the considerable, previously unrecognized degree of variation in this region. We identified 73 variations (65 SNPs, 8 indels that all are located outside of the RPS19 open reading frame, and of which 67.1% are classified as novel. We hypothesize that specific alleles in non-coding regions of RPS19 could alter the binding of regulatory proteins or transcription factors. Therefore, we carried out an extensive analysis to identify transcription factor binding sites (TFBS. A series of putative interaction sites coincide with detected variants. Sixteen of the corresponding transcription factors are of particular interest, as they are housekeeping genes or show a direct link to hematopoiesis, tumorigenesis or leukemia (e.g. GATA-1/2, PU.1, MZF-1.Specific alleles at predicted TFBSs may alter the expression of RPS19, modify an important interaction between transcription factors with overlapping TFBS or remove an important stimulus for hematopoiesis. We suggest that the detected interactions are of importance for hematopoiesis and could provide new insights into individual response to treatment.

  5. Differential genomic targeting of the transcription factor TAL1 in alternate haematopoietic lineages.

    Science.gov (United States)

    Palii, Carmen G; Perez-Iratxeta, Carolina; Yao, Zizhen; Cao, Yi; Dai, Fengtao; Davison, Jerry; Atkins, Harold; Allan, David; Dilworth, F Jeffrey; Gentleman, Robert; Tapscott, Stephen J; Brand, Marjorie

    2011-02-02

    TAL1/SCL is a master regulator of haematopoiesis whose expression promotes opposite outcomes depending on the cell type: differentiation in the erythroid lineage or oncogenesis in the T-cell lineage. Here, we used a combination of ChIP sequencing and gene expression profiling to compare the function of TAL1 in normal erythroid and leukaemic T cells. Analysis of the genome-wide binding properties of TAL1 in these two haematopoietic lineages revealed new insight into the mechanism by which transcription factors select their binding sites in alternate lineages. Our study shows limited overlap in the TAL1-binding profile between the two cell types with an unexpected preference for ETS and RUNX motifs adjacent to E-boxes in the T-cell lineage. Furthermore, we show that TAL1 interacts with RUNX1 and ETS1, and that these transcription factors are critically required for TAL1 binding to genes that modulate T-cell differentiation. Thus, our findings highlight a critical role of the cellular environment in modulating transcription factor binding, and provide insight into the mechanism by which TAL1 inhibits differentiation leading to oncogenesis in the T-cell lineage.

  6. Drug target mining and analysis of the Chinese tree shrew for pharmacological testing.

    Directory of Open Access Journals (Sweden)

    Feng Zhao

    Full Text Available The discovery of new drugs requires the development of improved animal models for drug testing. The Chinese tree shrew is considered to be a realistic candidate model. To assess the potential of the Chinese tree shrew for pharmacological testing, we performed drug target prediction and analysis on genomic and transcriptomic scales. Using our pipeline, 3,482 proteins were predicted to be drug targets. Of these predicted targets, 446 and 1,049 proteins with the highest rank and total scores, respectively, included homologs of targets for cancer chemotherapy, depression, age-related decline and cardiovascular disease. Based on comparative analyses, more than half of drug target proteins identified from the tree shrew genome were shown to be higher similarity to human targets than in the mouse. Target validation also demonstrated that the constitutive expression of the proteinase-activated receptors of tree shrew platelets is similar to that of human platelets but differs from that of mouse platelets. We developed an effective pipeline and search strategy for drug target prediction and the evaluation of model-based target identification for drug testing. This work provides useful information for future studies of the Chinese tree shrew as a source of novel targets for drug discovery research.

  7. Bootstrap Standard Error Estimates in Dynamic Factor Analysis

    Science.gov (United States)

    Zhang, Guangjian; Browne, Michael W.

    2010-01-01

    Dynamic factor analysis summarizes changes in scores on a battery of manifest variables over repeated measurements in terms of a time series in a substantially smaller number of latent factors. Algebraic formulae for standard errors of parameter estimates are more difficult to obtain than in the usual intersubject factor analysis because of the…

  8. What School Psychologists Need to Know about Factor Analysis

    Science.gov (United States)

    McGill, Ryan J.; Dombrowski, Stefan C.

    2017-01-01

    Factor analysis is a versatile class of psychometric techniques used by researchers to provide insight into the psychological dimensions (factors) that may account for the relationships among variables in a given dataset. The primary goal of a factor analysis is to determine a more parsimonious set of variables (i.e., fewer than the number of…

  9. Classification analysis of organization factors related to system safety

    International Nuclear Information System (INIS)

    Liu Huizhen; Zhang Li; Zhang Yuling; Guan Shihua

    2009-01-01

    This paper analyzes the different types of organization factors which influence the system safety. The organization factor can be divided into the interior organization factor and exterior organization factor. The latter includes the factors of political, economical, technical, law, social culture and geographical, and the relationships among different interest groups. The former includes organization culture, communication, decision, training, process, supervision and management and organization structure. This paper focuses on the description of the organization factors. The classification analysis of the organization factors is the early work of quantitative analysis. (authors)

  10. Landslide susceptibility analysis using Probabilistic Certainty Factor ...

    Indian Academy of Sciences (India)

    This paper reports the use of a GIS based Probabilistic Certainty Factor method to assess the geo-environmental factors that contribute to landslide susceptibility in Tevankarai Ar sub-watershed, Kodaikkanal. ... The results show that slope, aspect, soil and proximity to roads play important role in landslide susceptibility.

  11. Landslide susceptibility analysis using Probabilistic Certainty Factor ...

    Indian Academy of Sciences (India)

    This paper reports the use of a GIS based Probabilistic Certainty Factor method to assess the geo-environmental factors that contribute to landslide susceptibility in Tevankarai Ar sub-watershed,. Kodaikkanal. Landslide occurrences are a common phenomenon in the Tevankarai Ar sub-watershed,. Kodaikkanal owing to ...

  12. A Confirmatory Factor Analysis Approach to Construct Validation.

    Science.gov (United States)

    Rezmovic, Eva Lantos; Rezmovic, Victor

    1981-01-01

    A multitrait-multimethod matrix containing two methods of measuring 12 personality traits was analyzed and confirmatory factor analysis was applied to the data. Although unexplained variance remained, method factors and a general personality factor significantly improved the fit of a model containing only trait factors. (Author/RL)

  13. Whole-Genome Thermodynamic Analysis Reduces siRNA Off-Target Effects

    Science.gov (United States)

    Chen, Xi; Liu, Peng; Chou, Hui-Hsien

    2013-01-01

    Small interfering RNAs (siRNAs) are important tools for knocking down targeted genes, and have been widely applied to biological and biomedical research. To design siRNAs, two important aspects must be considered: the potency in knocking down target genes and the off-target effect on any nontarget genes. Although many studies have produced useful tools to design potent siRNAs, off-target prevention has mostly been delegated to sequence-level alignment tools such as BLAST. We hypothesize that whole-genome thermodynamic analysis can identify potential off-targets with higher precision and help us avoid siRNAs that may have strong off-target effects. To validate this hypothesis, two siRNA sets were designed to target three human genes IDH1, ITPR2 and TRIM28. They were selected from the output of two popular siRNA design tools, siDirect and siDesign. Both siRNA design tools have incorporated sequence-level screening to avoid off-targets, thus their output is believed to be optimal. However, one of the sets we tested has off-target genes predicted by Picky, a whole-genome thermodynamic analysis tool. Picky can identify off-target genes that may hybridize to a siRNA within a user-specified melting temperature range. Our experiments validated that some off-target genes predicted by Picky can indeed be inhibited by siRNAs. Similar experiments were performed using commercially available siRNAs and a few off-target genes were also found to be inhibited as predicted by Picky. In summary, we demonstrate that whole-genome thermodynamic analysis can identify off-target genes that are missed in sequence-level screening. Because Picky prediction is deterministic according to thermodynamics, if a siRNA candidate has no Picky predicted off-targets, it is unlikely to cause off-target effects. Therefore, we recommend including Picky as an additional screening step in siRNA design. PMID:23484018

  14. Genomic analysis of Campylobacter fetus subspecies: identification of candidate virulence determinants and diagnostic assay targets

    Directory of Open Access Journals (Sweden)

    Sanchez Daniel O

    2009-05-01

    Full Text Available Abstract Background Campylobacter fetus subspecies venerealis is the causative agent of bovine genital campylobacteriosis, asymptomatic in bulls the disease is spread to female cattle causing extensive reproductive loss. The microbiological and molecular differentiation of C. fetus subsp. venerealis from C. fetus subsp. fetus is extremely difficult. This study describes the analysis of the available C. fetus subsp. venerealis AZUL-94 strain genome (~75–80% to identify elements exclusively found in C. fetus subsp. venerealis strains as potential diagnostic targets and the characterisation of subspecies virulence genes. Results Eighty Kb of genomic sequence (22 contigs was identified as unique to C. fetus subsp. venerealis AZUL-94 and consisted of type IV secretory pathway components, putative plasmid genes and hypothetical proteins. Of the 9 PCR assays developed to target C. fetus subsp. venerealis type IV secretion system genes, 4 of these were specific for C. fetus subsp. venerealis biovar venerealis and did not detect C. fetus subsp. venerealis biovar intermedius. Two assays were specific for C. fetus subsp. venerealis AZUL-94 strain, with a further single assay specific for the AZUL-94 strain and C. fetus subsp. venerealis biovar intermedius (and not the remaining C. fetus subsp. venerealis biovar venerealis strains tested. C. fetus subsp. fetus and C. fetus subsp. venerealis were found to share most common Campylobacter virulence factors such as SAP, chemotaxis, flagellar biosynthesis, 2-component systems and cytolethal distending toxin subunits (A, B, C. We did not however, identify in C. fetus the full complement of bacterial adherence candidates commonly found in other Campylobacter spp. Conclusion The comparison of the available C. fetus subsp. venerealis genome sequence with the C. fetus subsp. fetus genome identified 80 kb of unique C. fetus subsp. venerealis AZUL94 sequence, with subsequent PCR confirmation demonstrating

  15. Risk factors for exclusive breastfeeding lasting less than two months-Identifying women in need of targeted breastfeeding support.

    Directory of Open Access Journals (Sweden)

    Karin Cato

    Full Text Available Breastfeeding rates in Sweden are declining, and it is important to identify women at risk for early cessation of exclusive breastfeeding.The aim of this study was to investigate factors associated with exclusive breastfeeding lasting less than two months postpartum.A population-based longitudinal study was conducted at Uppsala University Hospital, Sweden. Six hundred and seventy-nine women were included in this sub-study. Questionnaires were sent at five days, six weeks and six months postpartum, including questions on breastfeeding initiation and duration as well as several other background variables. The main outcome measure was exclusive breastfeeding lasting less than two months postpartum. Multivariable logistic regression analysis was used in order to calculate adjusted Odds Ratios (AOR and 95% Confidence Intervals (95% CI.Seventy-seven percent of the women reported exclusive breastfeeding at two months postpartum. The following variables in the multivariate regression analysis were independently associated with exclusive breastfeeding lasting less than two months postpartum: being a first time mother (AOR 2.15, 95% CI 1.32-3.49, reporting emotional distress during pregnancy (AOR 2.21, 95% CI 1.35-3.62 and giving birth by cesarean section (AOR 2.63, 95% CI 1.34-5.17.Factors associated with shorter exclusive breastfeeding duration were determined. Identification of women experiencing emotional distress during pregnancy, as well as scrutiny of caregiving routines on cesarean section need to be addressed, in order to give individual targeted breastfeeding support and promote longer breastfeeding duration.

  16. Comparative analysis of predicted plastid-targeted proteomes of sequenced higher plant genomes.

    Directory of Open Access Journals (Sweden)

    Scott Schaeffer

    Full Text Available Plastids are actively involved in numerous plant processes critical to growth, development and adaptation. They play a primary role in photosynthesis, pigment and monoterpene synthesis, gravity sensing, starch and fatty acid synthesis, as well as oil, and protein storage. We applied two complementary methods to analyze the recently published apple genome (Malus × domestica to identify putative plastid-targeted proteins, the first using TargetP and the second using a custom workflow utilizing a set of predictive programs. Apple shares roughly 40% of its 10,492 putative plastid-targeted proteins with that of the Arabidopsis (Arabidopsis thaliana plastid-targeted proteome as identified by the Chloroplast 2010 project and ∼57% of its entire proteome with Arabidopsis. This suggests that the plastid-targeted proteomes between apple and Arabidopsis are different, and interestingly alludes to the presence of differential targeting of homologs between the two species. Co-expression analysis of 2,224 genes encoding putative plastid-targeted apple proteins suggests that they play a role in plant developmental and intermediary metabolism. Further, an inter-specific comparison of Arabidopsis, Prunus persica (Peach, Malus × domestica (Apple, Populus trichocarpa (Black cottonwood, Fragaria vesca (Woodland Strawberry, Solanum lycopersicum (Tomato and Vitis vinifera (Grapevine also identified a large number of novel species-specific plastid-targeted proteins. This analysis also revealed the presence of alternatively targeted homologs across species. Two separate analyses revealed that a small subset of proteins, one representing 289 protein clusters and the other 737 unique protein sequences, are conserved between seven plastid-targeted angiosperm proteomes. Majority of the novel proteins were annotated to play roles in stress response, transport, catabolic processes, and cellular component organization. Our results suggest that the current state of

  17. EXPLORATORY FACTOR ANALYSIS (EFA IN CONSUMER BEHAVIOR AND MARKETING RESEARCH

    Directory of Open Access Journals (Sweden)

    Marcos Pascual Soler

    2012-06-01

    Full Text Available Exploratory Factor Analysis (EFA is one of the most widely used statistical procedures in social research. The main objective of this work is to describe the most common practices used by researchers in the consumer behavior and marketing area. Through a literature review methodology the practices of AFE in five consumer behavior and marketing journals(2000-2010 were analyzed. Then, the choices made by the researchers concerning factor model, retention criteria, rotation, factors interpretation and other relevant issues to factor analysis were analized. The results suggest that researchers routinely conduct analyses using such questionable methods. Suggestions for improving the use of factor analysis and the reporting of results are presented and a checklist (Exploratory Factor Analysis Checklist, EFAC is provided to help editors, reviewers, and authors improve reporting exploratory factor analysis.

  18. Factor analysis of serogroups botanica and aurisina of Leptospira biflexa.

    Science.gov (United States)

    Cinco, M

    1977-11-01

    Factor analysis is performed on serovars of Botanica and Aurisina serogroup of Leptospira biflexa. The results show the arrangement of main factors serovar and serogroup specific, as well as the antigens common with serovars of heterologous serogroups.

  19. A Bayesian Nonparametric Approach to Factor Analysis

    DEFF Research Database (Denmark)

    Piatek, Rémi; Papaspiliopoulos, Omiros

    2018-01-01

    This paper introduces a new approach for the inference of non-Gaussian factor models based on Bayesian nonparametric methods. It relaxes the usual normality assumption on the latent factors, widely used in practice, which is too restrictive in many settings. Our approach, on the contrary, does...... not impose any particular assumptions on the shape of the distribution of the factors, but still secures the basic requirements for the identification of the model. We design a new sampling scheme based on marginal data augmentation for the inference of mixtures of normals with location and scale...... restrictions. This approach is augmented by the use of a retrospective sampler, to allow for the inference of a constrained Dirichlet process mixture model for the distribution of the latent factors. We carry out a simulation study to illustrate the methodology and demonstrate its benefits. Our sampler is very...

  20. Using Factor Analysis to Generate Clusters of Agile Practices

    OpenAIRE

    Abbas, Noura; Gravell, Andy; Wills, Gary

    2010-01-01

    In this paper, factor analysis is applied on a set of data that was collected to study the effectiveness of 58 different agile practices. The analysis extracted 15 factors; each was associated with a list of practices. These factors with the associated practices can be used as a guide for agile process improvement. Correlations between the extracted factors were calculated, and the significant correlation findings suggested that people who applied iterative and incremental development and qua...

  1. Targeting the epidermal growth factor receptor in radiotherapy: radiobiological mechanisms, preclinical and clinical results

    International Nuclear Information System (INIS)

    Baumann, Michael; Krause, Mechthild

    2004-01-01

    Background and purpose: Inhibition of the epidermal growth factor receptor (EGFR) is a fastly developing field in preclinical and clinical cancer research. This review presents the current status of knowledge and discusses radiobiological mechanisms which may underly the efficacy of EGFR inhibitors combined with irradiation. Materials and methods: Preclinical and clinical results on combined targeting of the EGFR and irradiation from the literature and from this laboratory are reviewed. Focus is given to the radiobiological rationale of this approach and to endpoints of experimental radiotherapy. Results: Overexpression of the EGFR is associated with decreased local tumour control after radiotherapy, especially when the overall treatment time is long. Inhibition of the EGFR either alone or in combination with irradiation decreases the growth rate of tumours expressing this receptor. Preclinical data provide proof-of-principle that local tumour control may be improved by combining irradiation with C225 mAb. In a randomised phase III clinical trial, simultaneous irradiation and treatment with the EGFR antibody Cetuximab (Erbitux[reg]; C225) in head and neck cancer patients resulted in significantly improved locoregional tumour control and survival compared to curative irradiation alone. Acute skin reactions increased in the experimental arm. The underlying mechanisms of enhanced radiation effects of combined EGFR inhibition with irradiation and of the partly conflicting results in different studies are poorly understood. There is increasing evidence, that important intertumoral heterogeneity in the response to EGFR inhibition alone and combined with irradiation exists, which appears to be at least partly dependent on specific mutations of the receptor as well as of molecules that are involved in the intracellular signal transduction pathway. Conclusions and outlook: Further investigations at all levels of the translational research chain exploring the mechanisms of

  2. Spatial analysis of ecosystem service relationships to improve targeting of payments for hydrological services.

    Science.gov (United States)

    Mokondoko, Pierre; Manson, Robert H; Ricketts, Taylor H; Geissert, Daniel

    2018-01-01

    Payment for hydrological services (PHS) are popular tools for conserving ecosystems and their water-related services. However, improving the spatial targeting and impacts of PHS, as well as their ability to foster synergies with other ecosystem services (ES), remain challenging. We aimed at using spatial analyses to evaluate the targeting performance of México's National PHS program in central Veracruz. We quantified the effectiveness of areas targeted for PHS in actually covering areas of high HS provision and social priority during 2003-2013. First, we quantified provisioning and spatial distributions of two target (water yield and soil retention), and one non-target ES (carbon storage) using InVEST. Subsequently, pairwise relationships among ES were quantified by using spatial correlation and overlap analyses. Finally, we evaluated targeting by: (i) prioritizing areas of individual and overlapping ES; (ii) quantifying spatial co-occurrences of these priority areas with those targeted by PHS; (iii) evaluating the extent to which PHS directly contribute to HS delivery; and (iv), testing if PHS targeted areas disproportionately covered areas with high ecological and social priority. We found that modelled priority areas exhibited non-random distributions and distinct spatial patterns. Our results show significant pairwise correlations between all ES suggesting synergistic relationships. However, our analysis showed a significantly lower overlap than expected and thus significant mismatches between PHS targeted areas and all types of priority areas. These findings suggest that the targeting of areas with high HS provisioning and social priority by Mexico's PHS program could be improved significantly. This study underscores: (1) the importance of using maps of HS provisioning as main targeting criteria in PHS design to channel payments towards areas that require future conservation, and (2) the need for future research that helps balance ecological and socioeconomic

  3. An assessment of independent component analysis for detection of military targets from hyperspectral images

    Science.gov (United States)

    Tiwari, K. C.; Arora, M. K.; Singh, D.

    2011-10-01

    Hyperspectral data acquired over hundreds of narrow contiguous wavelength bands are extremely suitable for target detection due to their high spectral resolution. Though spectral response of every material is expected to be unique, but in practice, it exhibits variations, which is known as spectral variability. Most target detection algorithms depend on spectral modelling using a priori available target spectra In practice, target spectra is, however, seldom available a priori. Independent component analysis (ICA) is a new evolving technique that aims at finding out components which are statistically independent or as independent as possible. The technique therefore has the potential of being used for target detection applications. A assessment of target detection from hyperspectral images using ICA and other algorithms based on spectral modelling may be of immense interest, since ICA does not require a priori target information. The aim of this paper is, thus, to assess the potential of ICA based algorithm vis a vis other prevailing algorithms for military target detection. Four spectral matching algorithms namely Orthogonal Subspace Projection (OSP), Constrained Energy Minimisation (CEM), Spectral Angle Mapper (SAM) and Spectral Correlation Mapper (SCM), and four anomaly detection algorithms namely OSP anomaly detector (OSPAD), Reed-Xiaoli anomaly detector (RXD), Uniform Target Detector (UTD) and a combination of Reed-Xiaoli anomaly detector and Uniform Target Detector (RXD-UTD) were considered. The experiments were conducted using a set of synthetic and AVIRIS hyperspectral images containing aircrafts as military targets. A comparison of true positive and false positive rates of target detections obtained from ICA and other algorithms plotted on a receiver operating curves (ROC) space indicates the superior performance of the ICA over other algorithms.

  4. Identification of noise in linear data sets by factor analysis

    International Nuclear Information System (INIS)

    Roscoe, B.A.; Hopke, Ph.K.

    1982-01-01

    A technique which has the ability to identify bad data points, after the data has been generated, is classical factor analysis. The ability of classical factor analysis to identify two different types of data errors make it ideally suited for scanning large data sets. Since the results yielded by factor analysis indicate correlations between parameters, one must know something about the nature of the data set and the analytical techniques used to obtain it to confidentially isolate errors. (author)

  5. Novel snail1 target proteins in human colon cancer identified by proteomic analysis.

    Directory of Open Access Journals (Sweden)

    María Jesús Larriba

    2010-04-01

    Full Text Available The transcription factor Snail1 induces epithelial-to-mesenchymal transition (EMT, a process responsible for the acquisition of invasiveness during tumorigenesis. Several transcriptomic studies have reported Snail1-regulated genes in different cell types, many of them involved in cell adhesion. However, only a few studies have used proteomics as a tool for the characterization of proteins mediating EMT.We identified by proteomic analysis using 2D-DIGE electrophoresis combined with MALDI-TOF-TOF and ESI-linear ion trap mass spectrometry a number of proteins with variable functions whose expression is modulated by Snail1 in SW480-ADH human colon cancer cells. Validation was performed by Western blot and immunofluorescence analyses. Snail1 repressed several members of the 14-3-3 family of phosphoserine/phosphothreonine binding proteins and also the expression of the Proliferation-associated protein 2G4 (PA2G4 that was mainly localized at the nuclear Cajal bodies. In contrast, the expression of two proteins involved in RNA processing, the Cleavage and polyadenylation specificity factor subunit 6 (CPSF6 and the Splicing factor proline/glutamine-rich (SFPQ, was higher in Snail1-expressing cells than in controls. The regulation of 14-3-3epsilon, 14-3-3tau, 14-3-3zeta and PA2G4 by Snail1 was reproduced in HT29 colon cancer cells. In addition, we found an inverse correlation between 14-3-3sigma and Snail1 expression in human colorectal tumors.We have identified a set of novel Snail1 target proteins in colon cancer that expand the cellular processes affected by Snail1 and thus its relevance for cell function and phenotype.

  6. Sentiment analysis enhancement with target variable in Kumar’s Algorithm

    Science.gov (United States)

    Arman, A. A.; Kawi, A. B.; Hurriyati, R.

    2016-04-01

    Sentiment analysis (also known as opinion mining) refers to the use of text analysis and computational linguistics to identify and extract subjective information in source materials. Sentiment analysis is widely applied to reviews discussion that is being talked in social media for many purposes, ranging from marketing, customer service, or public opinion of public policy. One of the popular algorithm for Sentiment Analysis implementation is Kumar algorithm that developed by Kumar and Sebastian. Kumar algorithm can identify the sentiment score of the statement, sentence or tweet, but cannot determine the relationship of the object or target related to the sentiment being analysed. This research proposed solution for that challenge by adding additional component that represent object or target to the existing algorithm (Kumar algorithm). The result of this research is a modified algorithm that can give sentiment score based on a given object or target.

  7. 48 CFR 1615.404-70 - Profit analysis factors.

    Science.gov (United States)

    2010-10-01

    ... FEDERAL EMPLOYEES HEALTH BENEFITS ACQUISITION REGULATION CONTRACTING METHODS AND CONTRACT TYPES CONTRACTING BY NEGOTIATION Contract Pricing 1615.404-70 Profit analysis factors. (a) OPM contracting officers...

  8. Analysis of the Neutron Generator and Target for the LSDTS System

    Energy Technology Data Exchange (ETDEWEB)

    Park, Chang Je; Lee, Yong Deok; Song, Jae Hoon; Song, Kee Chan [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2008-11-15

    A preliminary analysis was performed based on the literatures and the patents for the neutron generators and targets for the lead slowing down time spectrometer (LSDTS) system. It was found that local neutron generator did not exhibit enough neutron intensity such as 1E+12 n/s, which is a minimum requirement for the LSDTS system to overcome curium backgrounds. However, a neutron generator implemented with an electron accelerator may provide a higher intensity around 1E+13 n/s and it is required to investigate further including a detail analysis. In addition to the neutron generator, a study on target was performed with the Monte Carlo simulation. In the study, an optimal design of target was suggested to provide a high neutron yield and a better thermal resistance. The suggested target consists several cylindrical plates with a certain cooling gap, which have increasing thickness and increasing radius.

  9. Analysis of the Neutron Generator and Target for the LSDTS System

    International Nuclear Information System (INIS)

    Park, Chang Je; Lee, Yong Deok; Song, Jae Hoon; Song, Kee Chan

    2008-11-01

    A preliminary analysis was performed based on the literatures and the patents for the neutron generators and targets for the lead slowing down time spectrometer (LSDTS) system. It was found that local neutron generator did not exhibit enough neutron intensity such as 1E+12 n/s, which is a minimum requirement for the LSDTS system to overcome curium backgrounds. However, a neutron generator implemented with an electron accelerator may provide a higher intensity around 1E+13 n/s and it is required to investigate further including a detail analysis. In addition to the neutron generator, a study on target was performed with the Monte Carlo simulation. In the study, an optimal design of target was suggested to provide a high neutron yield and a better thermal resistance. The suggested target consists several cylindrical plates with a certain cooling gap, which have increasing thickness and increasing radius

  10. Genome-wide analysis of PDX1 target genes in human pancreatic progenitors

    Directory of Open Access Journals (Sweden)

    Xianming Wang

    2018-03-01

    Full Text Available Objective: Homozygous loss-of-function mutations in the gene coding for the homeobox transcription factor (TF PDX1 leads to pancreatic agenesis, whereas heterozygous mutations can cause Maturity-Onset Diabetes of the Young 4 (MODY4. Although the function of Pdx1 is well studied in pre-clinical models during insulin-producing β-cell development and homeostasis, it remains elusive how this TF controls human pancreas development by regulating a downstream transcriptional program. Also, comparative studies of PDX1 binding patterns in pancreatic progenitors and adult β-cells have not been conducted so far. Furthermore, many studies reported the association between single nucleotide polymorphisms (SNPs and T2DM, and it has been shown that islet enhancers are enriched in T2DM-associated SNPs. Whether regions, harboring T2DM-associated SNPs are PDX1 bound and active at the pancreatic progenitor stage has not been reported so far. Methods: In this study, we have generated a novel induced pluripotent stem cell (iPSC line that efficiently differentiates into human pancreatic progenitors (PPs. Furthermore, PDX1 and H3K27ac chromatin immunoprecipitation sequencing (ChIP-seq was used to identify PDX1 transcriptional targets and active enhancer and promoter regions. To address potential differences in the function of PDX1 during development and adulthood, we compared PDX1 binding profiles from PPs and adult islets. Moreover, combining ChIP-seq and GWAS meta-analysis data we identified T2DM-associated SNPs in PDX1 binding sites and active chromatin regions. Results: ChIP-seq for PDX1 revealed a total of 8088 PDX1-bound regions that map to 5664 genes in iPSC-derived PPs. The PDX1 target regions include important pancreatic TFs, such as PDX1 itself, RFX6, HNF1B, and MEIS1, which were activated during the differentiation process as revealed by the active chromatin mark H3K27ac and mRNA expression profiling, suggesting that auto-regulatory feedback regulation

  11. The efficacy of targeted interventions for modifiable psychosocial risk factors of persistent nonspecific low back pain e A systematic review

    DEFF Research Database (Denmark)

    Kent, Peter; Kjær, Per

    2012-01-01

    were randomised controlled trials of targeted psychosocial interventions that used trial designs capable of providing robust information on the efficacy of targeted treatment (treatment effect modification) for the outcomes of pain, activity limitation and psychosocial factors (fear avoidance......, catastrophisation, anxiety and depression). Results and conclusion: Four studies met the inclusion criteria and collectively investigated nine hypotheses about targeted treatment on 28 subgroup/treatment outcomes. There were only two statistically significant results. Graded activity plus Treatment Based...... Classification targeted to people with high movement-related fear was more effective than Treatment Based Classification at reducing movement-related fear at 4 weeks. Active rehabilitation (physical exercise classes with cognitivebehavioural principles) was more effective than usual GP care at reducing activity...

  12. Novel targets of sulforaphane in primary cardiomyocytes identified by proteomic analysis.

    Science.gov (United States)

    Angeloni, Cristina; Turroni, Silvia; Bianchi, Laura; Fabbri, Daniele; Motori, Elisa; Malaguti, Marco; Leoncini, Emanuela; Maraldi, Tullia; Bini, Luca; Brigidi, Patrizia; Hrelia, Silvana

    2013-01-01

    Cardiovascular diseases represent the main cause of mortality in the industrialized world and the identification of effective preventive strategies is of fundamental importance. Sulforaphane, an isothiocyanate from cruciferous vegetables, has been shown to up-regulate phase II enzymes in cardiomyocytes and counteract oxidative stress-induced apoptosis. Aim of the present study was the identification and characterization of novel sulforaphane targets in cardiomyocytes applying a proteomic approach. Two-dimensional gel electrophoresis and mass spectrometry were used to generate protein profiles of primary neonatal rat cardiomyocytes treated and untreated with 5 µM sulforaphane for 1-48 h. According to image analysis, 64 protein spots were found as differentially expressed and their functional correlations were investigated using the MetaCore program. We mainly focused on 3 proteins: macrophage migration inhibitory factor (MIF), CLP36 or Elfin, and glyoxalase 1, due to their possible involvement in cardioprotection. Validation of the time-dependent differential expression of these proteins was performed by western blotting. In particular, to gain insight into the cardioprotective role of the modulation of glyoxalase 1 by sulforaphane, further experiments were performed using methylglyoxal to mimic glycative stress. Sulforaphane was able to counteract methylglyoxal-induced apoptosis, ROS production, and glycative stress, likely through glyoxalase 1 up-regulation. In this study, we reported for the first time new molecular targets of sulforaphane, such as MIF, CLP36 and glyoxalase 1. In particular, we gave new insights into the anti-glycative role of sulforaphane in cardiomyocytes, confirming its pleiotropic behavior in counteracting cardiovascular diseases.

  13. Inhibition of human immunodeficiency virus type 1 replication with artificial transcription factors targeting the highly conserved primer-binding site

    NARCIS (Netherlands)

    Eberhardy, Scott R.; Goncalves, Joao; Coelho, Sofia; Segal, David J.; Berkhout, Ben; Barbas, Carlos F.

    2006-01-01

    The human immunodeficiency virus type 1 (HIV-1) primer-binding site (PBS) is a highly conserved region in the HIV genome and represents an attractive target for the development of new anti-HIV therapies. In this study, we designed four artificial zinc finger transcription factors to bind at or

  14. Magnesium wasting associated with epidermal-growth-factor receptor-targeting antibodies in colorectal cancer: a prospective study.

    NARCIS (Netherlands)

    Tejpar, S.; Piessevaux, H.; Claes, K.; Piront, P.; Hoenderop, J.G.J.; Verslype, C.; Cutsem, E. van

    2007-01-01

    BACKGROUND: Preliminary evidence suggests that magnesium wasting occurs in patients who are treated with epidermal-growth-factor receptor (EGFR)-targeting antibodies for colorectal cancer. The mechanism of this side-effect is unknown, and if all or a subset of patients are affected is also unclear.

  15. Target preparation and neutron activation analysis: a successful story at IRMM

    International Nuclear Information System (INIS)

    Robouch, P.; Arana, G.; Eguskiza, M.; Maguregui, M.I.; Pomme, S.; Ingelbrecht, C.

    2002-01-01

    The main task of a target producer is to make well characterized and homogeneous deposits on specific supports. Alpha and/or gamma spectrometry are traditionally used to monitor the quality of actinide deposits. With the increasing demand for enriched stable isotope targets, other analytical techniques, such as ICP-MS and NAA, are needed. This paper presents the application of neutron activation analysis to quality control of 'thin' targets, 'thicker' neutron dosimeters and 'thick' bronze disks prepared by the Reference Materials Unit at the Institute of Reference Materials and Measurements

  16. Target preparation and neutron activation analysis a successful story at IRMM

    CERN Document Server

    Robouch, P; Eguskiza, M; Maguregui, M I; Pommé, S; Ingelbrecht, C

    2002-01-01

    The main task of a target producer is to make well characterized and homogeneous deposits on specific supports. Alpha and/or gamma spectrometry are traditionally used to monitor the quality of actinide deposits. With the increasing demand for enriched stable isotope targets, other analytical techniques, such as ICP-MS and NAA, are needed. This paper presents the application of neutron activation analysis to quality control of 'thin' targets, 'thicker' neutron dosimeters and 'thick' bronze disks prepared by the Reference Materials Unit at the Institute of Reference Materials and Measurements.

  17. Bevacizumab reduces tumor targeting of antiepidermal growth factor and anti-insulin-like growth factor 1 receptor antibodies

    NARCIS (Netherlands)

    Heskamp, Sandra; Boerman, Otto C.; Molkenboer-Kuenen, Janneke D. M.; Oyen, Wim J. G.; van der Graaf, Winette T. A.; van Laarhoven, Hanneke W. M.

    2013-01-01

    Bevacizumab (antivascular endothelial growth factor [anti-VEGF]) and cetuximab (antiepidermal growth factor receptor [anti-EGFR]) are approved antibodies for treatment of cancer. However, in advanced colorectal cancer, the combination fails to improve survival. As the reason for the lack of activity

  18. Surface water quality assessment using factor analysis

    African Journals Online (AJOL)

    2006-01-16

    Jan 16, 2006 ... factors extracted by the Centroid method, rotated by Varimax rotation (Ahmed et al., 2005). Calculated eigenvalues, per cent. Figure 1. Sketch map of water quality monitoring stations in Buyuk. Menderes Basin in Turkey. TABLE 1. Descriptive statistics of water quality data under low-flow conditions. Variable.

  19. Warranty claim analysis considering human factors

    International Nuclear Information System (INIS)

    Wu Shaomin

    2011-01-01

    Warranty claims are not always due to product failures. They can also be caused by two types of human factors. On the one hand, consumers might claim warranty due to misuse and/or failures caused by various human factors. Such claims might account for more than 10% of all reported claims. On the other hand, consumers might not be bothered to claim warranty for failed items that are still under warranty, or they may claim warranty after they have experienced several intermittent failures. These two types of human factors can affect warranty claim costs. However, research in this area has received rather little attention. In this paper, we propose three models to estimate the expected warranty cost when the two types of human factors are included. We consider two types of failures: intermittent and fatal failures, which might result in different claim patterns. Consumers might report claims after a fatal failure has occurred, and upon intermittent failures they might report claims after a number of failures have occurred. Numerical examples are given to validate the results derived.

  20. Chiral analysis of baryon form factors

    Energy Technology Data Exchange (ETDEWEB)

    Gail, T.A.

    2007-11-08

    This work presents an extensive theoretical investigation of the structure of the nucleon within the standard model of elementary particle physics. In particular, the long range contributions to a number of various form factors parametrizing the interactions of the nucleon with an electromagnetic probe are calculated. The theoretical framework for those calculations is chiral perturbation theory, the exact low energy limit of Quantum Chromo Dynamics, which describes such long range contributions in terms of a pion-cloud. In this theory, a nonrelativistic leading one loop order calculation of the form factors parametrizing the vector transition of a nucleon to its lowest lying resonance, the {delta}, a covariant calculation of the isovector and isoscalar vector form factors of the nucleon at next to leading one loop order and a covariant calculation of the isoscalar and isovector generalized vector form factors of the nucleon at leading one loop order are performed. In order to perform consistent loop calculations in the covariant formulation of chiral perturbation theory an appropriate renormalization scheme is defined in this work. All theoretical predictions are compared to phenomenology and results from lattice QCD simulations. These comparisons allow for a determination of the low energy constants of the theory. Furthermore, the possibility of chiral extrapolation, i.e. the extrapolation of lattice data from simulations at large pion masses down to the small physical pion mass is studied in detail. Statistical as well as systematic uncertainties are estimated for all results throughout this work. (orig.)

  1. [High risk factors analysis of stillbirth].

    Science.gov (United States)

    Xiong, Y; Xia, H X; Wang, Y S; Lin, X L; Zhu, T T; Zhao, Y; Li, X T

    2017-12-25

    Objective: To explore the high risk factors of stillbirth. Methods: 176 cases of stillbirth were collected in the Obstetrics and Gynecology Hospital of Fudan University from January 1(st), 2010 to December 31(st), 2016. All cases were analyzed retrospectively, including general profile, high risk factors of stillbirth in different years and pregnancy periods. Results: (1) The incidence of stillbirth was 0.178%(176/98 785). Stillbirth occured mostly at 28-28(+6) gestational weeks (10.8%,19/176), and the second peak was 29-29(+6) weeks(10.2%,18/176), while the third common period was 37-37(+6) weeks (9.1%,16/176). After 39 weeks, it maintained at a low level. (2) The top 5 high risk factors of stillbirth were infection (18.2%,32/176), unexplained (13.6%,24/176), hypertention disorders in pregnancy (13.1%, 23/176), umbilical cord torsion (12.5%, 22/176) and fetal malformations (10.2%, 18/176). (3) From 2010 to 2012, the top 3 high risk factors were unexplained, the umbilical cord torsion and infection, while hypertention in pregnancy, infection and fetal malformation became the top 3 high risk factors after 2013. (4) Early stillbirth (20-27(+6) weeks) accounted for 21.6%(38/176); and unexplained (47.4%, 18/38), fetal edema (13.2%, 5/38),infection (13.2%, 5/38), umbilical cord torsion (5.3%, 2/38) were the top 4 high risk factors. Late stillbirth (≥28 weeks) accounted for 78.4%(138/176), with infection (19.6%,27/138), hypertention in pregnancy (15.9%,22/138), umbilical cord torsion (14.5%,20/138) and fetal malformation(12.3%,17/138)being the top 4 high risk factors. Conclusions: More attention should be paid to maternal complications, especially infection and hypertension in pregnancy. Antenatal fetal monitoring, timely termination of pregnancy, standard management of stillbirth and looking for the causes may help reduce the incidence of stillbirth.

  2. Transcriptome-Wide Analysis of Botrytis elliptica Responsive microRNAs and Their Targets in Lilium Regale Wilson by High-Throughput Sequencing and Degradome Analysis

    Directory of Open Access Journals (Sweden)

    Xue Gao

    2017-05-01

    Full Text Available MicroRNAs, as master regulators of gene expression, have been widely identified and play crucial roles in plant-pathogen interactions. A fatal pathogen, Botrytis elliptica, causes the serious folia disease of lily, which reduces production because of the high susceptibility of most cultivated species. However, the miRNAs related to Botrytis infection of lily, and the miRNA-mediated gene regulatory networks providing resistance to B. elliptica in lily remain largely unexplored. To systematically dissect B. elliptica-responsive miRNAs and their target genes, three small RNA libraries were constructed from the leaves of Lilium regale, a promising Chinese wild Lilium species, which had been subjected to mock B. elliptica treatment or B. elliptica infection for 6 and 24 h. By high-throughput sequencing, 71 known miRNAs belonging to 47 conserved families and 24 novel miRNA were identified, of which 18 miRNAs were downreguleted and 13 were upregulated in response to B. elliptica. Moreover, based on the lily mRNA transcriptome, 22 targets for 9 known and 1 novel miRNAs were identified by the degradome sequencing approach. Most target genes for elliptica-responsive miRNAs were involved in metabolic processes, few encoding different transcription factors, including ELONGATION FACTOR 1 ALPHA (EF1a and TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR 2 (TCP2. Furthermore, the expression patterns of a set of elliptica-responsive miRNAs and their targets were validated by quantitative real-time PCR. This study represents the first transcriptome-based analysis of miRNAs responsive to B. elliptica and their targets in lily. The results reveal the possible regulatory roles of miRNAs and their targets in B. elliptica interaction, which will extend our understanding of the mechanisms of this disease in lily.

  3. Malware Analysis: From Large-Scale Data Triage to Targeted Attack Recognition (Dagstuhl Seminar 17281)

    OpenAIRE

    Zennou, Sarah; Debray, Saumya K.; Dullien, Thomas; Lakhothia, Arun

    2018-01-01

    This report summarizes the program and the outcomes of the Dagstuhl Seminar 17281, entitled "Malware Analysis: From Large-Scale Data Triage to Targeted Attack Recognition". The seminar brought together practitioners and researchers from industry and academia to discuss the state-of-the art in the analysis of malware from both a big data perspective and a fine grained analysis. Obfuscation was also considered. The meeting created new links within this very diverse community.

  4. HER-2 as a Progression Factor and Therapeutic Target in Breast Cancer

    National Research Council Canada - National Science Library

    1999-01-01

    ...). We had observed previously that upon reduction of llER-2 in MCF-7 cells by ribozyme-targeting estradiol lost its ability to induce anchorage- independent colony formation in soft agar of the tumor cell...

  5. Workplace bullying as sensemaking: An analysis of target and actor perspectives on initial hostile interactions

    Czech Academy of Sciences Publication Activity Database

    Zábrodská, Kateřina; Ellwood, C.; Zaemdaar, S.; Mudrák, Jiří

    2016-01-01

    Roč. 22, č. 2 (2016), s. 136-157 ISSN 1475-9551 R&D Projects: GA ČR GPP407/10/P146; GA ČR GA14-02098S Institutional support: RVO:68081740 Keywords : workplace bullying * workplace hostility * sensemaking * target * actor * collective biography * stories Subject RIV: AN - Psychology Impact factor: 0.489, year: 2016

  6. Effectiveness of a selective alcohol prevention program targeting personality risk factors: Results of interaction analyses.

    Science.gov (United States)

    Lammers, Jeroen; Goossens, Ferry; Conrod, Patricia; Engels, Rutger; Wiers, Reinout W; Kleinjan, Marloes

    2017-08-01

    To explore whether specific groups of adolescents (i.e., scoring high on personality risk traits, having a lower education level, or being male) benefit more from the Preventure intervention with regard to curbing their drinking behaviour. A clustered randomized controlled trial, with participants randomly assigned to a 2-session coping skills intervention or a control no-intervention condition. Fifteen secondary schools throughout The Netherlands; 7 schools in the intervention and 8 schools in the control condition. 699 adolescents aged 13-15; 343 allocated to the intervention and 356 to the control condition; with drinking experience and elevated scores in either negative thinking, anxiety sensitivity, impulsivity or sensation seeking. Differential effectiveness of the Preventure program was examined for the personality traits group, education level and gender on past-month binge drinking (main outcome), binge frequency, alcohol use, alcohol frequency and problem drinking, at 12months post-intervention. Preventure is a selective school-based alcohol prevention programme targeting personality risk factors. The comparator was a no-intervention control. Intervention effects were moderated by the personality traits group and by education level. More specifically, significant intervention effects were found on reducing alcohol use within the anxiety sensitivity group (OR=2.14, CI=1.40, 3.29) and reducing binge drinking (OR=1.76, CI=1.38, 2.24) and binge drinking frequency (β=0.24, p=0.04) within the sensation seeking group at 12months post-intervention. Also, lower educated young adolescents reduced binge drinking (OR=1.47, CI=1.14, 1.88), binge drinking frequency (β=0.25, p=0.04), alcohol use (OR=1.32, CI=1.06, 1.65) and alcohol use frequency (β=0.47, p=0.01), but not those in the higher education group. Post hoc latent-growth analyses revealed significant effects on the development of binge drinking (β=-0.19, p=0.02) and binge drinking frequency (β=-0.10, p=0

  7. Regression analysis of nuclear plant capacity factors

    International Nuclear Information System (INIS)

    Stocks, K.J.; Faulkner, J.I.

    1980-07-01

    Operating data on all commercial nuclear power plants of the PWR, HWR, BWR and GCR types in the Western World are analysed statistically to determine whether the explanatory variables size, year of operation, vintage and reactor supplier are significant in accounting for the variation in capacity factor. The results are compared with a number of previous studies which analysed only United States reactors. The possibility of specification errors affecting the results is also examined. Although, in general, the variables considered are statistically significant, they explain only a small portion of the variation in the capacity factor. The equations thus obtained should certainly not be used to predict the lifetime performance of future large reactors

  8. Stromal Activation Associated with Development of Prostate Cancer in Prostate-Targeted Fibroblast Growth Factor 8b Transgenic Mice

    Directory of Open Access Journals (Sweden)

    Teresa D. Elo

    2010-11-01

    Full Text Available Expression of fibroblast growth factor 8 (FGF-8 is commonly increased in prostate cancer. Experimental studies have provided evidence that it plays a role in prostate tumorigenesis and tumor progression. To study how increased FGF-8 affects the prostate, we generated and analyzed transgenic (TG mice expressing FGF-8b under the probasin promoter that targets expression to prostate epithelium. Prostates of the TG mice showed an increased size and changes in stromal and epithelialmorphology progressing fromatypia and prostatic intraepithelial neoplasia (mouse PIN, mPIN lesions to tumors with highly variable phenotype bearing features of adenocarcinoma, carcinosarcoma, and sarcoma. The development of mPIN lesions was preceded by formation of activated stroma containing increased proportion of fibroblastic cells, rich vasculature, and inflammation. The association between advancing stromal and epithelial alterations was statistically significant. Microarray analysis and validation with quantitative polymerase chain reaction revealed that expression of osteopontin and connective tissue growth factor was markedly upregulated in TG mouse prostates compared with wild type prostates. Androgen receptor staining was decreased in transformed epithelium and in hypercellular stroma but strongly increased in the sarcoma-like lesions. In conclusion, our data demonstrate that disruption of FGF signaling pathways by increased epithelial production of FGF-8b leads to strongly activated and atypical stroma, which precedes development of mPIN lesions and prostate cancer with mixed features of adenocarcinoma and sarcoma in the prostates of TG mice. The results suggest that increased FGF-8 in human prostate may also contribute to prostate tumorigenesis by stromal activation.

  9. Nuclear microbeam analysis of ICF target material made by GDP technique

    Energy Technology Data Exchange (ETDEWEB)

    Rong, C.; He, X. [Applied Ion Beam Physics Laboratory, Institute of Modern Physics, Department of Nuclear Science and Technology, Fudan University, Shanghai 200433 (China); Meng, J., E-mail: eleanor920@163.com [Research Center of Laser Fusion, CAEP, Mianyang 621000 (China); Gao, D. [Research Center of Laser Fusion, CAEP, Mianyang 621000 (China); Zhang, Y.; Li, X.; Lyu, H.; Zhu, Y. [Applied Ion Beam Physics Laboratory, Institute of Modern Physics, Department of Nuclear Science and Technology, Fudan University, Shanghai 200433 (China); Zheng, Y. [Shanghai Synchrotron Radiation Facility, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201204 (China); Wang, X. [Applied Ion Beam Physics Laboratory, Institute of Modern Physics, Department of Nuclear Science and Technology, Fudan University, Shanghai 200433 (China); Shen, H., E-mail: haoshen@fudan.edu.cn [Applied Ion Beam Physics Laboratory, Institute of Modern Physics, Department of Nuclear Science and Technology, Fudan University, Shanghai 200433 (China)

    2015-04-01

    Germanium doped carbon–hydrogen polymer (CH) by Glow Discharge Polymer (GDP) technique has become the preferred Inertial Confinement Fusion (ICF) target material. The nondestructive measurement of elements content in the ICF target has become a significant work in recent years. This paper presents the compositional and distributional results of the Germanium doped CH analysis. The Ge doped CH materials as thin film and as hollow sphere were investigated by the Rutherford Backscattering Spectroscopy (RBS) combined with the particle induced X-ray emission (PIXE) and the Elastic Recoil Detection Analysis (ERDA). The samples are thin film with 36 μm thickness and ICF target with 500–2000 μm diameter. The calibration and geometrical arrangement in the analysis of spherical target should be carefully considered in order to acquire accurate results. In the work, the uniformity of the sphere is shown and the ratio of carbon, hydrogen and germanium has been measured. The ratio values are in good agreement with the results obtained by the combustion method. In addition, the difference of the composition from thin film to hollow sphere is also discussed. This work demonstrates that nuclear microbeam analysis is an ideal method to evaluate the ICF target quality.

  10. Genome-Wide Analysis of miRNA targets in Brachypodium and Biomass Energy Crops

    Energy Technology Data Exchange (ETDEWEB)

    Green, Pamela J. [Univ. of Delaware, Newark, DE (United States)

    2015-08-11

    MicroRNAs (miRNAs) contribute to the control of numerous biological processes through the regulation of specific target mRNAs. Although the identities of these targets are essential to elucidate miRNA function, the targets are much more difficult to identify than the small RNAs themselves. Before this work, we pioneered the genome-wide identification of the targets of Arabidopsis miRNAs using an approach called PARE (German et al., Nature Biotech. 2008; Nature Protocols, 2009). Under this project, we applied PARE to Brachypodium distachyon (Brachypodium), a model plant in the Poaceae family, which includes the major food grain and bioenergy crops. Through in-depth global analysis and examination of specific examples, this research greatly expanded our knowledge of miRNAs and target RNAs of Brachypodium. New regulation in response to environmental stress or tissue type was found, and many new miRNAs were discovered. More than 260 targets of new and known miRNAs with PARE sequences at the precise sites of miRNA-guided cleavage were identified and characterized. Combining PARE data with the small RNA data also identified the miRNAs responsible for initiating approximately 500 phased loci, including one of the novel miRNAs. PARE analysis also revealed that differentially expressed miRNAs in the same family guide specific target RNA cleavage in a correspondingly tissue-preferential manner. The project included generation of small RNA and PARE resources for bioenergy crops, to facilitate ongoing discovery of conserved miRNA-target RNA regulation. By associating specific miRNA-target RNA pairs with known physiological functions, the research provides insights about gene regulation in different tissues and in response to environmental stress. This, and release of new PARE and small RNA data sets should contribute basic knowledge to enhance breeding and may suggest new strategies for improvement of biomass energy crops.

  11. Statistical analysis of target motion in gated lung stereotactic body radiation therapy

    International Nuclear Information System (INIS)

    Zhao Bo; Yang Yong; Li Tianfang; Li Xiang; Heron, Dwight E; Huq, M Saiful

    2011-01-01

    An external surrogate-based respiratory gating technique is a useful method to reduce target margins for the treatment of a moving lung tumor. The success of this technique relies on a good correlation between the motion of the external markers and the internal tumor as well as the repeatability of the respiratory motion. In gated lung stereotactic body radiation therapy (SBRT), the treatment time for each fraction could exceed 30 min due to large fractional dose. Tumor motion may experience pattern changes such as baseline shift during such extended treatment time. The purpose of this study is to analyze tumor motion traces in actual treatment situations and to evaluate the effect of the target baseline shift in gated lung SBRT treatment. Real-time motion data for both the external markers and tumors from 51 lung SBRT treatments with Cyberknife Synchrony technology were analyzed in this study. The treatment time is typically greater than 30 min. The baseline shift was calculated with a rolling average window equivalent to ∼20 s and subtracted from that at the beginning. The magnitude of the baseline shift and its relationship with treatment time were investigated. Phase gating simulation was retrospectively performed on 12 carefully selected treatments with respiratory amplitude larger than 5 mm and regular phases. A customized gating window was defined for each individual treatment. It was found that the baseline shifts are specific to each patient and each fraction. Statistical analysis revealed that more than 69% treatments exhibited increased baseline shifts with the lapse of treatment time. The magnitude of the baseline shift could reach 5.3 mm during a 30 min treatment. Gating simulation showed that tumor excursion was caused mainly by the uncertainties in phase gating simulation and baseline shift, the latter being the primary factor. With a 5 mm gating window, 2 out of 12 treatments in the study group showed significant tumor excursion. Baseline shifts

  12. Numerical analysis of free surface instabilities in the IFMIF lithium target

    Energy Technology Data Exchange (ETDEWEB)

    Gordeev, S.; Heinzel, V. [Research Centre of Karlsruhe (Germany). Inst. for Reactor Safety; Moeslang, A. [Research Centre of Karlsruhe (Germany). Inst. for Material Research I

    2007-07-01

    The International Fusion Materials Facility (IFMIF) facility uses a high speed (10-20 m/s) Lithium (Li) jet flow as a target for two 40 MeV/125 mA deuteron beams. The major function of the Li target is to provide a stable Li jet for the production of an intense neutron flux. For the understanding the lithium jet behaviour and elimination of the free-surface flow instabilities a detailed analysis of the Li jet flow is necessary. Different kinds of instability mechanisms in the liquid jet flow have been evaluated and classified based on analytical and experimental data. Numerical investigations of the target free surface flow have been performed. Previous numerical investigations have shown in principle the suitability of CFD code Star- CD for the simulation of the Li-target flow. The main objective of this study is detailed numerical analysis of instabilities in the Li-jet flow caused by boundary layer relaxation near the nozzle exit, transition to the turbulence flow and back wall curvature. A number of CFD models are developed to investigate the formation of instabilities on the target surface. Turbulence models are validated on the experimental data. Experimental observations have shown that the change of the nozzle geometry at the outlet such as a slight divergence of the nozzle surfaces or nozzle edge defects causes the flow separation and occurrence of longitudinal periodic structures on the free surface with an amplitude up to 5 mm. Target surface fluctuations of this magnitude can lead to the penetration of the deuteron beam in the target structure and cause the local overheating of the back plat. Analysis of large instabilities in the Li-target flow combined with the heat distribution in lithium depending on the free surface shape is performed in this study. (orig.)

  13. Numerical analysis of free surface instabilities in the IFMIF lithium target

    International Nuclear Information System (INIS)

    Gordeev, S.; Heinzel, V.; Moeslang, A.

    2007-01-01

    The International Fusion Materials Facility (IFMIF) facility uses a high speed (10-20 m/s) Lithium (Li) jet flow as a target for two 40 MeV/125 mA deuteron beams. The major function of the Li target is to provide a stable Li jet for the production of an intense neutron flux. For the understanding the lithium jet behaviour and elimination of the free-surface flow instabilities a detailed analysis of the Li jet flow is necessary. Different kinds of instability mechanisms in the liquid jet flow have been evaluated and classified based on analytical and experimental data. Numerical investigations of the target free surface flow have been performed. Previous numerical investigations have shown in principle the suitability of CFD code Star- CD for the simulation of the Li-target flow. The main objective of this study is detailed numerical analysis of instabilities in the Li-jet flow caused by boundary layer relaxation near the nozzle exit, transition to the turbulence flow and back wall curvature. A number of CFD models are developed to investigate the formation of instabilities on the target surface. Turbulence models are validated on the experimental data. Experimental observations have shown that the change of the nozzle geometry at the outlet such as a slight divergence of the nozzle surfaces or nozzle edge defects causes the flow separation and occurrence of longitudinal periodic structures on the free surface with an amplitude up to 5 mm. Target surface fluctuations of this magnitude can lead to the penetration of the deuteron beam in the target structure and cause the local overheating of the back plat. Analysis of large instabilities in the Li-target flow combined with the heat distribution in lithium depending on the free surface shape is performed in this study. (orig.)

  14. Two Computer Programs for Factor Analysis. Technical Note Number 41.

    Science.gov (United States)

    Wisler, Carl E.

    Two factor analysis algorithms, previously described by P. Horst, have been programed for use on the General Electric Time-Sharing Computer System. The first of these, Principal Components Analysis (PCA), uses the Basic Structure Successive Factor Method With Residual Matrices algorithm to obtain the principal component vectors of a correlation…

  15. The Mixer: Introducing the Concept of Factor Analysis

    Science.gov (United States)

    Segrist, Dan J.; Pawlow, Laura A.

    2007-01-01

    This study entailed the development and implementation of a classroom activity designed to introduce students to the concept of factor analysis. We implemented the activity in both a personality theories course and a tests and measurements course. Data suggest that students learned about factor analysis from this activity, while enjoying it.…

  16. A Factor Analysis of the BSRI and the PAQ.

    Science.gov (United States)

    Edwards, Teresa A.; And Others

    Factor analysis of the Bem Sex Role Inventory (BSRI) and the Personality Attributes Questionnaire (PAQ) was undertaken to study the independence of the masculine and feminine scales within each instrument. Both instruments were administered to undergraduate education majors. Analysis of primary first and second order factors of the BSRI indicated…

  17. Exploratory Factor Analysis of a Force Concept Inventory Data Set

    Science.gov (United States)

    Scott, Terry F.; Schumayer, Daniel; Gray, Andrew R.

    2012-01-01

    We perform a factor analysis on a "Force Concept Inventory" (FCI) data set collected from 2109 respondents. We address two questions: the appearance of conceptual coherence in student responses to the FCI and some consequences of this factor analysis on the teaching of Newtonian mechanics. We will highlight the apparent conflation of Newton's…

  18. Therapeutic effect of photodynamic therapy combined with targeted delivery of silencing vascular endothelial growth factor (Conference Presentation)

    Science.gov (United States)

    Hsu, Yih-Chih

    2016-03-01

    Photodynamic therapy is a novel therapeutic modality to treat cancer by using a photosensitizer which is activated by a light source to produce reactive oxygen species and mediates tumours oxygen-independent hypoxic conditions. Vascular endothelial growth factor (VEGF) is one of the primary factors that affect tumor angiogenesis. Another emerging treatment to cure cancer is the use of interference RNA to silence a specific mRNA sequence. Such treatment requires a delivery system such as liposomes. The nanoparticle size measured was about 30 nm. Cellular uptake study was performed to verify that the nanoparticles have a sigma receptor mediated pathway. Non-targeted LCP NPs did not show significant difference with or without haloperidol but has a lower intensity as than targeted LCP NPs. These results confirm that LCP NPs have a receptor mediated pathway. Cell viability was found to decrease at 25 nM of transfected VEGF siRNA. Combined therapy of PDT and VEGF siRNA showed significant response as compared with PDT and gene therapy alone. In vivo toxicity assay with mice treated with targeted LCP NPs containing control siRNA or VEGF siRNA and non-targeted LCP NPs containing VEGF siRNA did not show any significant difference with the PBS injected group which suggests that there is no toxicity with the dose. It suggests that PDT combined with targeted gene therapy has a potential mean to achieve better therapeutic outcome.

  19. Likelihood-Based Confidence Intervals in Exploratory Factor Analysis

    NARCIS (Netherlands)

    Oort, Frans J.

    2011-01-01

    In exploratory or unrestricted factor analysis, all factor loadings are free to be estimated. In oblique solutions, the correlations between common factors are free to be estimated as well. The purpose of this article is to show how likelihood-based confidence intervals can be obtained for rotated

  20. Factor analysis in hydrochemical survey | Ephraim | Global Journal ...

    African Journals Online (AJOL)

    When subjected to factor analysis, the analytical data of water samples of the Calabar Flank area was transformed into factor score sets that are considered most consistent with known geological and environmental processes, and appropriate to the limits of analytical precision. Factor I reflects geochemical interactions of ...

  1. Likelihood-based confidence intervals in exploratory factor analysis

    NARCIS (Netherlands)

    Oort, F.J.

    2011-01-01

    In exploratory or unrestricted factor analysis, all factor loadings are free to be estimated. In oblique solutions, the correlations between common factors are free to be estimated as well. The purpose of this article is to show how likelihood-based confidence intervals can be obtained for rotated

  2. A kernel version of spatial factor analysis

    DEFF Research Database (Denmark)

    Nielsen, Allan Aasbjerg

    2009-01-01

    Based on work by Pearson in 1901, Hotelling in 1933 introduced principal component analysis (PCA). PCA is often used for general feature generation and linear orthogonalization or compression by dimensionality reduction of correlated multivariate data, see Jolliffe for a comprehensive description...

  3. Bootstrap Confidence Intervals for Ordinary Least Squares Factor Loadings and Correlations in Exploratory Factor Analysis

    Science.gov (United States)

    Zhang, Guangjian; Preacher, Kristopher J.; Luo, Shanhong

    2010-01-01

    This article is concerned with using the bootstrap to assign confidence intervals for rotated factor loadings and factor correlations in ordinary least squares exploratory factor analysis. Coverage performances of "SE"-based intervals, percentile intervals, bias-corrected percentile intervals, bias-corrected accelerated percentile…

  4. Transient analysis mode participation for modal survey target mode selection using MSC/NASTRAN DMAP

    Science.gov (United States)

    Barnett, Alan R.; Ibrahim, Omar M.; Sullivan, Timothy L.; Goodnight, Thomas W.

    1994-01-01

    Many methods have been developed to aid analysts in identifying component modes which contribute significantly to component responses. These modes, typically targeted for dynamic model correlation via a modal survey, are known as target modes. Most methods used to identify target modes are based on component global dynamic behavior. It is sometimes unclear if these methods identify all modes contributing to responses important to the analyst. These responses are usually those in areas of hardware design concerns. One method used to check the completeness of target mode sets and identify modes contributing significantly to important component responses is mode participation. With this method, the participation of component modes in dynamic responses is quantified. Those modes which have high participation are likely modal survey target modes. Mode participation is most beneficial when it is used with responses from analyses simulating actual flight events. For spacecraft, these responses are generated via a structural dynamic coupled loads analysis. Using MSC/NASTRAN DMAP, a method has been developed for calculating mode participation based on transient coupled loads analysis results. The algorithm has been implemented to be compatible with an existing coupled loads methodology and has been used successfully to develop a set of modal survey target modes.

  5. Transient analysis mode participation for modal survey target mode selection using MSC/NASTRAN DMAP

    Science.gov (United States)

    Barnett, Alan R.; Ibrahim, Omar M.; Sullivan, Timothy L.; Goodnight, Thomas W.

    1994-03-01

    Many methods have been developed to aid analysts in identifying component modes which contribute significantly to component responses. These modes, typically targeted for dynamic model correlation via a modal survey, are known as target modes. Most methods used to identify target modes are based on component global dynamic behavior. It is sometimes unclear if these methods identify all modes contributing to responses important to the analyst. These responses are usually those in areas of hardware design concerns. One method used to check the completeness of target mode sets and identify modes contributing significantly to important component responses is mode participation. With this method, the participation of component modes in dynamic responses is quantified. Those modes which have high participation are likely modal survey target modes. Mode participation is most beneficial when it is used with responses from analyses simulating actual flight events. For spacecraft, these responses are generated via a structural dynamic coupled loads analysis. Using MSC/NASTRAN DMAP, a method has been developed for calculating mode participation based on transient coupled loads analysis results. The algorithm has been implemented to be compatible with an existing coupled loads methodology and has been used successfully to develop a set of modal survey target modes.

  6. Targeting c-kit receptor in neuroblastomas and colorectal cancers using stem cell factor (SCF)-based recombinant bacterial toxins.

    Science.gov (United States)

    Choudhary, Swati; Pardo, Alessa; Rosinke, Reinhard; Batra, Janendra K; Barth, Stefan; Verma, Rama S

    2016-01-01

    Autocrine activation of c-kit (KIT receptor tyrosine kinase) has been postulated to be a potent oncogenic driver in small cell lung cancer, neuroblastoma (NB), and poorly differentiated colorectal carcinoma (CRC). Although targeted therapy involving tyrosine kinase inhibitors (TKIs) such as imatinib mesylate is highly effective for gastrointestinal stromal tumor carrying V560G c-kit mutation, it does not show much potential for targeting wild-type KIT (WT-KIT). Our study demonstrates the role of stem cell factor (SCF)-based toxin conjugates for targeting WT-KIT-overexpressing malignancies such as NBs and CRCs. We constructed SCF-based recombinant bacterial toxins by genetically fusing mutated form of natural ligand SCF to receptor binding deficient forms of Diphtheria toxin (DT) or Pseudomonas exotoxin A (ETA') and evaluated their efficacy in vitro. Efficient targeting was achieved in all receptor-positive neuroblastoma (IMR-32 and SHSY5Y) and colon cancer cell lines (COLO 320DM, HCT 116, and DLD-1) but not in receptor-negative breast carcinoma cell line (MCF-7) thereby proving specificity. While dose- and time-dependent cytotoxicity was observed in both neuroblastoma cell lines, COLO 320DM and HCT 116 cells, only an anti-proliferative effect was observed in DLD-1 cells. We prove that these novel targeting agents have promising potential as KIT receptor tyrosine kinase targeting system.

  7. Network based transcription factor analysis of regenerating axolotl limbs

    Directory of Open Access Journals (Sweden)

    Cameron Jo Ann

    2011-03-01

    Full Text Available Abstract Background Studies on amphibian limb regeneration began in the early 1700's but we still do not completely understand the cellular and molecular events of this unique process. Understanding a complex biological process such as limb regeneration is more complicated than the knowledge of the individual genes or proteins involved. Here we followed a systems biology approach in an effort to construct the networks and pathways of protein interactions involved in formation of the accumulation blastema in regenerating axolotl limbs. Results We used the human orthologs of proteins previously identified by our research team as bait to identify the transcription factor (TF pathways and networks that regulate blastema formation in amputated axolotl limbs. The five most connected factors, c-Myc, SP1, HNF4A, ESR1 and p53 regulate ~50% of the proteins in our data. Among these, c-Myc and SP1 regulate 36.2% of the proteins. c-Myc was the most highly connected TF (71 targets. Network analysis showed that TGF-β1 and fibronectin (FN lead to the activation of these TFs. We found that other TFs known to be involved in epigenetic reprogramming, such as Klf4, Oct4, and Lin28 are also connected to c-Myc and SP1. Conclusions Our study provides a systems biology approach to how different molecular entities inter-connect with each other during the formation of an accumulation blastema in regenerating axolotl limbs. This approach provides an in silico methodology to identify proteins that are not detected by experimental methods such as proteomics but are potentially important to blastema formation. We found that the TFs, c-Myc and SP1 and their target genes could potentially play a central role in limb regeneration. Systems biology has the potential to map out numerous other pathways that are crucial to blastema formation in regeneration-competent limbs, to compare these to the pathways that characterize regeneration-deficient limbs and finally, to identify stem

  8. Human factor analysis and preventive countermeasures in nuclear power plant

    International Nuclear Information System (INIS)

    Li Ye

    2010-01-01

    Based on the human error analysis theory and the characteristics of maintenance in a nuclear power plant, human factors of maintenance in NPP are divided into three different areas: human, technology, and organization. Which is defined as individual factors, including psychological factors, physiological characteristics, health status, level of knowledge and interpersonal skills; The technical factors including technology, equipment, tools, working order, etc.; The organizational factors including management, information exchange, education, working environment, team building and leadership management,etc The analysis found that organizational factors can directly or indirectly affect the behavior of staff and technical factors, is the most basic human error factor. Based on this nuclear power plant to reduce human error and measures the response. (authors)

  9. Factors influencing crime rates: an econometric analysis approach

    Science.gov (United States)

    Bothos, John M. A.; Thomopoulos, Stelios C. A.

    2016-05-01

    The scope of the present study is to research the dynamics that determine the commission of crimes in the US society. Our study is part of a model we are developing to understand urban crime dynamics and to enhance citizens' "perception of security" in large urban environments. The main targets of our research are to highlight dependence of crime rates on certain social and economic factors and basic elements of state anticrime policies. In conducting our research, we use as guides previous relevant studies on crime dependence, that have been performed with similar quantitative analyses in mind, regarding the dependence of crime on certain social and economic factors using statistics and econometric modelling. Our first approach consists of conceptual state space dynamic cross-sectional econometric models that incorporate a feedback loop that describes crime as a feedback process. In order to define dynamically the model variables, we use statistical analysis on crime records and on records about social and economic conditions and policing characteristics (like police force and policing results - crime arrests), to determine their influence as independent variables on crime, as the dependent variable of our model. The econometric models we apply in this first approach are an exponential log linear model and a logit model. In a second approach, we try to study the evolvement of violent crime through time in the US, independently as an autonomous social phenomenon, using autoregressive and moving average time-series econometric models. Our findings show that there are certain social and economic characteristics that affect the formation of crime rates in the US, either positively or negatively. Furthermore, the results of our time-series econometric modelling show that violent crime, viewed solely and independently as a social phenomenon, correlates with previous years crime rates and depends on the social and economic environment's conditions during previous years.

  10. Interactions between the R2R3-MYB transcription factor, AtMYB61, and target DNA binding sites.

    Directory of Open Access Journals (Sweden)

    Michael B Prouse

    Full Text Available Despite the prominent roles played by R2R3-MYB transcription factors in the regulation of plant gene expression, little is known about the details of how these proteins interact with their DNA targets. For example, while Arabidopsis thaliana R2R3-MYB protein AtMYB61 is known to alter transcript abundance of a specific set of target genes, little is known about the specific DNA sequences to which AtMYB61 binds. To address this gap in knowledge, DNA sequences bound by AtMYB61 were identified using cyclic amplification and selection of targets (CASTing. The DNA targets identified using this approach corresponded to AC elements, sequences enriched in adenosine and cytosine nucleotides. The preferred target sequence that bound with the greatest affinity to AtMYB61 recombinant protein was ACCTAC, the AC-I element. Mutational analyses based on the AC-I element showed that ACC nucleotides in the AC-I element served as the core recognition motif, critical for AtMYB61 binding. Molecular modelling predicted interactions between AtMYB61 amino acid residues and corresponding nucleotides in the DNA targets. The affinity between AtMYB61 and specific target DNA sequences did not correlate with AtMYB61-driven transcriptional activation with each of the target sequences. CASTing-selected motifs were found in the regulatory regions of genes previously shown to be regulated by AtMYB61. Taken together, these findings are consistent with the hypothesis that AtMYB61 regulates transcription from specific cis-acting AC elements in vivo. The results shed light on the specifics of DNA binding by an important family of plant-specific transcriptional regulators.

  11. ANALYSIS OF RISK FACTORS ECTOPIC PREGNANCY

    Directory of Open Access Journals (Sweden)

    Budi Santoso

    2017-04-01

    Full Text Available Introduction: Ectopic pregnancy is a pregnancy with extrauterine implantation. This situation is gynecologic emergency that contributes to maternal mortality. Therefore, early recognition, based on identification of the causes of ectopic pregnancy risk factors, is needed. Methods: The design descriptive observational. The samples were pregnant women who had ectopic pregnancy at Maternity Room, Emergency Unit, Dr. Soetomo Hospital, Surabaya, from 1 July 2008 to 1 July 2010. Sampling technique was total sampling using medical records. Result: Patients with ectopic pregnancy were 99 individuals out of 2090 pregnant women who searched for treatment in Dr. Soetomo Hospital. However, only 29 patients were accompanied with traceable risk factors. Discussion:. Most ectopic pregnancies were in the age group of 26-30 years, comprising 32 patients (32.32%, then in age groups of 31–35 years as many as 25 patients (25.25%, 18 patients in age group 21–25 years (18.18%, 17 patients in age group 36–40 years (17.17%, 4 patients in age group 41 years and more (4.04%, and the least was in age group of 16–20 years with 3 patients (3.03%. A total of 12 patients with ectopic pregnancy (41.38% had experience of abortion and 6 patients (20.69% each in groups of patients with ectopic pregnancy who used family planning, in those who used family planning as well as ectopic pregnancy patients with history of surgery. There were 2 patients (6.90% of the group of patients ectopic pregnancy who had history of surgery and history of abortion. The incidence rate of ectopic pregnancy was 4.73%, mostly in the second gravidity (34.34%, whereas the nulliparous have the highest prevalence of 39.39%. Acquired risk factors, i.e. history of operations was 10.34%, patients with family planning 20.69%, patients with history of abortion 41.38%, patients with history of abortion and operation 6.90% patients with family and history of abortion was 20.69%.

  12. Investigating product development strategy in beverage industry using factor analysis

    Directory of Open Access Journals (Sweden)

    Naser Azad

    2013-03-01

    Full Text Available Selecting a product development strategy that is associated with the company's current service or product innovation, based on customers’ needs and changing environment, plays an important role in increasing demand, increasing market share, increasing sales and profits. Therefore, it is important to extract effective variables associated with product development to improve performance measurement of firms. This paper investigates important factors influencing product development strategies using factor analysis. The proposed model of this paper investigates 36 factors and, using factor analysis, we extract six most influential factors including information sharing, intelligence information, exposure strategy, differentiation, research and development strategy and market survey. The first strategy, partnership, includes five sub-factor including product development partnership, partnership with foreign firms, customers’ perception from competitors’ products, Customer involvement in product development, inter-agency coordination, customer-oriented approach to innovation and transmission of product development change where inter-agency coordination has been considered the most important factor. Internal strengths are the most influential factors impacting the second strategy, intelligence information. The third factor, introducing strategy, introducing strategy, includes four sub criteria and consumer buying behavior is the most influencing factor. Differentiation is the next important factor with five components where knowledge and expertise in product innovation is the most important one. Research and development strategy with four sub-criteria where reducing product development cycle plays the most influential factor and finally, market survey strategy is the last important factor with three factors and finding new market plays the most important role.

  13. A resource for characterizing genome-wide binding and putative target genes of transcription factors expressed during secondary growth and wood formation in Populus.

    Science.gov (United States)

    Liu, Lijun; Ramsay, Trevor; Zinkgraf, Matthew; Sundell, David; Street, Nathaniel Robert; Filkov, Vladimir; Groover, Andrew

    2015-06-01

    Identifying transcription factor target genes is essential for modeling the transcriptional networks underlying developmental processes. Here we report a chromatin immunoprecipitation sequencing (ChIP-seq) resource consisting of genome-wide binding regions and associated putative target genes for four Populus homeodomain transcription factors expressed during secondary growth and wood formation. Software code (programs and scripts) for processing the Populus ChIP-seq data are provided within a publically available iPlant image, including tools for ChIP-seq data quality control and evaluation adapted from the human Encyclopedia of DNA Elements (ENCODE) project. Basic information for each transcription factor (including members of Class I KNOX, Class III HD ZIP, BEL1-like families) binding are summarized, including the number and location of binding regions, distribution of binding regions relative to gene features, associated putative target genes, and enriched functional categories of putative target genes. These ChIP-seq data have been integrated within the Populus Genome Integrative Explorer (PopGenIE) where they can be analyzed using a variety of web-based tools. We present an example analysis that shows preferential binding of transcription factor ARBORKNOX1 to the nearest neighbor genes in a pre-calculated co-expression network module, and enrichment for meristem-related genes within this module including multiple orthologs of Arabidopsis KNOTTED-like Arabidopsis 2/6. © 2015 Society for Experimental Biology and John Wiley & Sons Ltd This article has been contributed to by US Government employees and their work is in the public domain in the USA.

  14. Factor analysis of dynamic radionuclide studies

    International Nuclear Information System (INIS)

    Barber, D.C.; Nijran, K.S.

    1982-01-01

    In this paper it has been assumed that theory space is generated from a theoretical model. In cases where a theoretical model cannot be given there would appear to be no obvious reason why theory space cannot be generated from a population of curves derived from careful manual analysis of many studies. The method could therefore be trained to extract the curves of interest even in the absence of a sound theoretical model of the physiological processes being investigated. The use of this method for more interesting types of study such as renograms is currently being investigated

  15. Gene expression meta-analysis identifies metastatic pathways and transcription factors in breast cancer

    International Nuclear Information System (INIS)

    Thomassen, Mads; Tan, Qihua; Kruse, Torben A

    2008-01-01

    Metastasis is believed to progress in several steps including different pathways but the determination and understanding of these mechanisms is still fragmentary. Microarray analysis of gene expression patterns in breast tumors has been used to predict outcome in recent studies. Besides classification of outcome, these global expression patterns may reflect biological mechanisms involved in metastasis of breast cancer. Our purpose has been to investigate pathways and transcription factors involved in metastasis by use of gene expression data sets. We have analyzed 8 publicly available gene expression data sets. A global approach, 'gene set enrichment analysis' as well as an approach focusing on a subset of significantly differently regulated genes, GenMAPP, has been applied to rank pathway gene sets according to differential regulation in metastasizing tumors compared to non-metastasizing tumors. Meta-analysis has been used to determine overrepresentation of pathways and transcription factors targets, concordant deregulated in metastasizing breast tumors, in several data sets. The major findings are up-regulation of cell cycle pathways and a metabolic shift towards glucose metabolism reflected in several pathways in metastasizing tumors. Growth factor pathways seem to play dual roles; EGF and PDGF pathways are decreased, while VEGF and sex-hormone pathways are increased in tumors that metastasize. Furthermore, migration, proteasome, immune system, angiogenesis, DNA repair and several signal transduction pathways are associated to metastasis. Finally several transcription factors e.g. E2F, NFY, and YY1 are identified as being involved in metastasis. By pathway meta-analysis many biological mechanisms beyond major characteristics such as proliferation are identified. Transcription factor analysis identifies a number of key factors that support central pathways. Several previously proposed treatment targets are identified and several new pathways that may

  16. Staphylococcus aureus hijacks a skin commensal to intensify its virulence: immunization targeting β-hemolysin and CAMP factor.

    Science.gov (United States)

    Lo, Chih-Wei; Lai, Yiu-Kay; Liu, Yu-Tsueng; Gallo, Richard L; Huang, Chun-Ming

    2011-02-01

    The need for a new anti-Staphylococcus aureus therapy that can effectively cripple bacterial infection, neutralize secretory virulence factors, and lower the risk of creating bacterial resistance is undisputed. Here, we propose what is, to our knowledge, a previously unreported infectious mechanism by which S. aureus may commandeer Propionibacterium acnes, a key member of the human skin microbiome, to spread its invasion and highlight two secretory virulence factors (S. aureus β-hemolysin and P. acnes CAMP (Christie, Atkins, Munch-Peterson) factor) as potential molecular targets for immunotherapy against S. aureus infection. Our data demonstrate that the hemolysis and cytolysis by S. aureus were noticeably augmented when S. aureus was grown with P. acnes. The augmentation was significantly abrogated when the P. acnes CAMP factor was neutralized or β-hemolysin of S. aureus was mutated. In addition, the hemolysis and cytolysis of recombinant β-hemolysin were markedly enhanced by recombinant CAMP factor. Furthermore, P. acnes exacerbated S. aureus-induced skin lesions in vivo. The combination of CAMP factor neutralization and β-hemolysin immunization cooperatively suppressed the skin lesions caused by coinfection of P. acnes and S. aureus. These observations suggest a previously unreported immunotherapy targeting the interaction of S. aureus with a skin commensal.

  17. TRAC analysis of design basis events for the accelerator production of tritium target/blanket

    International Nuclear Information System (INIS)

    Lin, J.C.; Elson, J.

    1997-01-01

    A two-loop primary cooling system with a residual heat removal system was designed to mitigate the heat generated in the tungsten neutron source rods inside the rungs of the ladders and the shell of the rungs. The Transient Reactor Analysis Code (TRAC) was used to analyze the thermal-hydraulic behavior of the primary cooling system during a pump coastdown transient; a cold-leg, large-break loss-of-coolant accident (LBLOCA); a hot-leg LBLOCA; and a target downcomer LBLOCA. The TRAC analysis results showed that the heat generated in the tungsten neutron source rods can be mitigated by the primary cooling system for the pump coastdown transient and all the LBLOCAs except the target downcomer LBLOCA. For the target downcomer LBLOCA, a cavity flood system is required to fill the cavity with water at a level above the large fixed headers

  18. Nucleolar targeting of proteins by the tandem array of basic amino acid stretches identified in the RNA polymerase I-associated factor PAF49

    International Nuclear Information System (INIS)

    Ushijima, Ryujiro; Matsuyama, Toshifumi; Nagata, Izumi; Yamamoto, Kazuo

    2008-01-01

    There is accumulating evidence to indicate that the regulation of subnuclear compartmentalization plays important roles in cellular processes. The RNA polymerase I-associated factor PAF49 has been shown to accumulate in the nucleolus in growing cells, but disperse into the nucleoplasm in growth-arrested cells. Serial deletion analysis revealed that amino acids 199-338 were necessary for the nucleolar localization of PAF49. Combinatorial point mutation analysis indicated that the individual basic amino acid stretches (BS) within the central (BS1-4) and the C-terminal (BS5 and 6) regions may cooperatively confer the nucleolar localization of PAF49. Addition of the basic stretches in tandem to a heterologous protein, such as the interferon regulatory factor-3, translocated the tagged protein into the nucleolus, even in the presence of an intrinsic nuclear export sequence. Thus, tandem array of the basic amino acid stretches identified here functions as a dominant nucleolar targeting sequence

  19. Identification of novel Pax8 targets in FRTL-5 thyroid cells by gene silencing and expression microarray analysis.

    Directory of Open Access Journals (Sweden)

    Tina Di Palma

    Full Text Available The differentiation program of thyroid follicular cells (TFCs, by far the most abundant cell population of the thyroid gland, relies on the interplay between sequence-specific transcription factors and transcriptional coregulators with the basal transcriptional machinery of the cell. However, the molecular mechanisms leading to the fully differentiated thyrocyte are still the object of intense study. The transcription factor Pax8, a member of the Paired-box gene family, has been demonstrated to be a critical regulator required for proper development and differentiation of thyroid follicular cells. Despite being Pax8 well-characterized with respect to its role in regulating genes involved in thyroid differentiation, genomics approaches aiming at the identification of additional Pax8 targets are lacking and the biological pathways controlled by this transcription factor are largely unknown.To identify unique downstream targets of Pax8, we investigated the genome-wide effect of Pax8 silencing comparing the transcriptome of silenced versus normal differentiated FRTL-5 thyroid cells. In total, 2815 genes were found modulated 72 h after Pax8 RNAi, induced or repressed. Genes previously reported to be regulated by Pax8 in FRTL-5 cells were confirmed. In addition, novel targets genes involved in functional processes such as DNA replication, anion transport, kinase activity, apoptosis and cellular processes were newly identified. Transcriptome analysis highlighted that Pax8 is a key molecule for thyroid morphogenesis and differentiation.This is the first large-scale study aimed at the identification of new genes regulated by Pax8, a master regulator of thyroid development and differentiation. The biological pathways and target genes controlled by Pax8 will have considerable importance to understand thyroid disease progression as well as to set up novel therapeutic strategies.

  20. Identification of Novel Pax8 Targets in FRTL-5 Thyroid Cells by Gene Silencing and Expression Microarray Analysis

    Science.gov (United States)

    Di Palma, Tina; Conti, Anna; de Cristofaro, Tiziana; Scala, Serena; Nitsch, Lucio; Zannini, Mariastella

    2011-01-01

    Background The differentiation program of thyroid follicular cells (TFCs), by far the most abundant cell population of the thyroid gland, relies on the interplay between sequence-specific transcription factors and transcriptional coregulators with the basal transcriptional machinery of the cell. However, the molecular mechanisms leading to the fully differentiated thyrocyte are still the object of intense study. The transcription factor Pax8, a member of the Paired-box gene family, has been demonstrated to be a critical regulator required for proper development and differentiation of thyroid follicular cells. Despite being Pax8 well-characterized with respect to its role in regulating genes involved in thyroid differentiation, genomics approaches aiming at the identification of additional Pax8 targets are lacking and the biological pathways controlled by this transcription factor are largely unknown. Methodology/Principal Findings To identify unique downstream targets of Pax8, we investigated the genome-wide effect of Pax8 silencing comparing the transcriptome of silenced versus normal differentiated FRTL-5 thyroid cells. In total, 2815 genes were found modulated 72 h after Pax8 RNAi, induced or repressed. Genes previously reported to be regulated by Pax8 in FRTL-5 cells were confirmed. In addition, novel targets genes involved in functional processes such as DNA replication, anion transport, kinase activity, apoptosis and cellular processes were newly identified. Transcriptome analysis highlighted that Pax8 is a key molecule for thyroid morphogenesis and differentiation. Conclusions/Significance This is the first large-scale study aimed at the identification of new genes regulated by Pax8, a master regulator of thyroid development and differentiation. The biological pathways and target genes controlled by Pax8 will have considerable importance to understand thyroid disease progression as well as to set up novel therapeutic strategies. PMID:21966443

  1. Application of factor analysis to the water quality in reservoirs

    Science.gov (United States)

    Silva, Eliana Costa e.; Lopes, Isabel Cristina; Correia, Aldina; Gonçalves, A. Manuela

    2017-06-01

    In this work we present a Factor Analysis of chemical and environmental variables of the water column and hydro-morphological features of several Portuguese reservoirs. The objective is to reduce the initial number of variables, keeping their common characteristics. Using the Factor Analysis, the environmental variables measured in the epilimnion and in the hypolimnion, together with the hydromorphological characteristics of the dams were reduced from 63 variables to only 13 factors, which explained a total of 83.348% of the variance in the original data. After performing rotation using the Varimax method, the relations between the factors and the original variables got clearer and more explainable, which provided a Factor Analysis model for these environmental variables using 13 varifactors: Water quality and distance to the source, Hypolimnion chemical composition, Sulfite-reducing bacteria and nutrients, Coliforms and faecal streptococci, Reservoir depth, Temperature, Location, among other factors.

  2. Deep sequencing analysis of small noncoding RNA and mRNA targets of the global post-transcriptional regulator, Hfq

    DEFF Research Database (Denmark)

    Sittka, A; Lucchini, S; Papenfort, K

    2008-01-01

    Recent advances in high-throughput pyrosequencing (HTPS) technology now allow a thorough analysis of RNA bound to cellular proteins, and, therefore, of post-transcriptional regulons. We used HTPS to discover the Salmonella RNAs that are targeted by the common bacterial Sm-like protein, Hfq. Initial...... transcriptomic analysis revealed that Hfq controls the expression of almost a fifth of all Salmonella genes, including several horizontally acquired pathogenicity islands (SPI-1, -2, -4, -5), two sigma factor regulons, and the flagellar gene cascade. Subsequent HTPS analysis of 350,000 cDNAs, derived from RNA co...... would be rescued by overexpression of HilD and FlhDC, and we proved this to be correct. The combination of epitope-tagging and HTPS of immunoprecipitated RNA detected the expression of many intergenic chromosomal regions of Salmonella. Our approach overcomes the limited availability of high...

  3. Iranian Voice Quality of Life Profile (IVQLP): Factor Analysis.

    Science.gov (United States)

    Dehqan, Ali; Yadegari, Fariba; Scherer, Ronald C; Asgari, Ali; Dabirmoghadam, Payman

    2017-09-01

    An important domain in health-related quality of life evaluations is quality of life perceptions due to having a voice disorder. The objective of this study was to examine the factor structure of the Iranian Voice Quality of Life Profile (IVQLP) based on Exploratory Factor Analysis and confirmatory factor analysis. The study sample consisted of 280 patients (174 males and 106 females) diagnosed with MTD, benign organic disorders such as polyps and nodules, and unilateral vocal fold paralysis and cancer. To evaluate the different dimensions of the IVQLP, a principal component analysis (PCA) was conducted. Confirmatory factor analysis (CFA) was used to investigate the fitting of extracted dimensions and construct validity of the IVQLP. The results showed that the IVQLP has a 4-factor structure. The first factor has 17 items and refers to Emotions. The second factor has 12 items and refers to Individual/Social Relations. The third factor with 6 items refers to Occupation, and the forth with 5 items relates to Psychosomatic characteristics. The conclusion of this study is that the concept of quality of life in Iranian patients with voice disorders is somewhat different from that of Western patients. This difference can be seen in. the large number of items related to an Emotional factor and the identification of a Psychosomatic factor. Copyright © 2017 The Voice Foundation. All rights reserved.

  4. In Vivo Phosphoproteomics Analysis Reveals the Cardiac Targets of β-Adrenergic Receptor Signaling

    DEFF Research Database (Denmark)

    Lundby, Alicia; Andersen, Martin N; Steffensen, Annette B

    2013-01-01

    -X-X-pS/T), and integrative analysis of sequence motifs and interaction networks suggested that the kinases AMPK (adenosine 5'-monophosphate-activated protein kinase), Akt, and mTOR (mammalian target of rapamycin) mediate βAR signaling, in addition to the well-established pathways mediated by PKA (cyclic adenosine...

  5. Doing Televised Rhetorical Analysis as a Means of Promoting College Awareness in a Target Market.

    Science.gov (United States)

    Schnell, Jim

    This paper describes aspects of doing televised rhetorical analysis as they relate to the promotion of college awareness in a particular target market. Considerations in the paper include variables that most professors encounter in their efforts to address the "service" expectations of their employment and how these variables can be…

  6. Analysis of shots on target and goals scored in soccer matches ...

    African Journals Online (AJOL)

    The aim of this study was to analyse the characteristics and patterns of shots on target and goals scored during the 2012-European Championship. The broadcasted matches were recorded and converted into electronic video files for a computerbased analysis. This quantitative study examined 31 matches of the ...

  7. [A guide on the use of factor analysis in the assessment of construct validity].

    Science.gov (United States)

    Kang, Hyuncheol

    2013-10-01

    The purpose of this study is to provide researchers with a simplified approach to undertaking exploratory factor analysis for the assessment of construct validity. All articles published in 2010, 2011, and 2012 in Journal of Korean Academy of Nursing were reviewed and other relevant books and articles were chosen for the review. In this paper, the following were discussed: preliminary analysis process of exploratory factor analysis to examine the sample size, distribution of measured variables, correlation coefficient, and results of KMO measure and Bartlett's test of sphericity. In addition, other areas to be considered in using factor analysis are discussed, including determination of the number of factors, the choice of rotation method or extraction method of the factor structure, and the interpretation of the factor loadings and explained variance. Content validity is the degree to which elements of an assessment instrument are relevant to and representative of the targeted construct for a particular assessment purpose. This measurement is difficult and challenging and takes a lot of time. Factor analysis is considered one of the strongest approaches to establishing construct validity and is the most commonly used method for establishing construct validity measured by an instrument.

  8. Using exploratory factor analysis in personality research: Best-practice recommendations

    Directory of Open Access Journals (Sweden)

    Sumaya Laher

    2010-11-01

    Research purpose: This article presents more objective methods to determine the number of factors, most notably parallel analysis and Velicer’s minimum average partial (MAP. The benefits of rotation are also discussed. The article argues for more consistent use of Procrustes rotation and congruence coefficients in factor analytic studies. Motivation for the study: Exploratory factor analysis is often criticised for not being rigorous and objective enough in terms of the methods used to determine the number of factors, the rotations to be used and ultimately the validity of the factor structure. Research design, approach and method: The article adopts a theoretical stance to discuss the best-practice recommendations for factor analytic research in the field of psychology. Following this, an example located within personality assessment and using the NEO-PI-R specifically is presented. A total of 425 students at the University of the Witwatersrand completed the NEO-PI-R. These responses were subjected to a principal components analysis using varimax rotation. The rotated solution was subjected to a Procrustes rotation with Costa and McCrae’s (1992 matrix as the target matrix. Congruence coefficients were also computed. Main findings: The example indicates the use of the methods recommended in the article and demonstrates an objective way of determining the number of factors. It also provides an example of Procrustes rotation with coefficients of agreement as an indication of how factor analytic results may be presented more rigorously in local research. Practical/managerial implications: It is hoped that the recommendations in this article will have best-practice implications for both researchers and practitioners in the field who employ factor analysis regularly. Contribution/value-add: This article will prove useful to all researchers employing factor analysis and has the potential to set the trend for better use of factor analysis in the South African context.

  9. Analysis of Deregulated microRNAs and Their Target Genes in Gastric Cancer.

    Directory of Open Access Journals (Sweden)

    Simonas Juzėnas

    Full Text Available MicroRNAs (miRNAs are widely studied non-coding RNAs that modulate gene expression. MiRNAs are deregulated in different tumors including gastric cancer (GC and have potential diagnostic and prognostic implications. The aim of our study was to determine miRNA profile in GC tissues, followed by evaluation of deregulated miRNAs in plasma of GC patients. Using available databases and bioinformatics methods we also aimed to evaluate potential target genes of confirmed differentially expressed miRNA and validate these findings in GC tissues.The study included 51 GC patients and 51 controls. Initially, we screened miRNA expression profile in 13 tissue samples of GC and 12 normal gastric tissues with TaqMan low density array (TLDA. In the second stage, differentially expressed miRNAs were validated in a replication cohort using qRT-PCR in tissue and plasma samples. Subsequently, we analyzed potential target genes of deregulated miRNAs using bioinformatics approach, determined their expression in GC tissues and performed correlation analysis with targeting miRNAs.Profiling with TLDA revealed 15 deregulated miRNAs in GC tissues compared to normal gastric mucosa. Replication analysis confirmed that miR-148a-3p, miR-204-5p, miR-223-3p and miR-375 were consistently deregulated in GC tissues. Analysis of GC patients' plasma samples showed significant down-regulation of miR-148a-3p, miR-375 and up-regulation of miR-223-3p compared to healthy subjects. Further, using bioinformatic tools we identified targets of replicated miRNAs and performed disease-associated gene enrichment analysis. Ultimately, we evaluated potential target gene BCL2 and DNMT3B expression by qRT-PCR in GC tissue, which correlated with targeting miRNA expression.Our study revealed miRNA profile in GC tissues and showed that miR-148a-3p, miR-223-3p and miR-375 are deregulated in GC plasma samples, but these circulating miRNAs showed relatively weak diagnostic performance as sole biomarkers

  10. Analysis of factors associated with cracked teeth.

    Science.gov (United States)

    Seo, Deog-Gyu; Yi, Young-Ah; Shin, Su-Jung; Park, Jeong-Won

    2012-03-01

    The purpose of this study was to analyze the characteristics, distribution, and associated factors of longitudinal fractured teeth according to the well-defined criteria of the American Association of Endodontists (AAE). One hundred seven teeth with longitudinal fracture from 103 patients were diagnosed and analyzed. The patients' signs, symptoms, age, and sex were noted as well as the tooth number, dental arch, filling materials, size/classification of restoration, crack direction, pulp vitality, whether the patient had undergone endodontic treatment, bite test results, percussion test results, wear facet, and periodontal pocket depth. Eighty-seven teeth were diagnosed with a cracked tooth (81.3%), 14 were diagnosed with vertical root fracture (VRF, 13.1%), 4 had a split tooth (3.7%), and 2 had a fractured cusp (1.9%); 82.2% showed a sensitive reaction on the bite test. Longitudinal tooth fractures were observed most frequently in patient in their 40s. The upper first molar (28.0%) was most frequently cracked, followed by the lower first molar (25.2%), the lower second molar (20.6%), and the upper second molar (16.8%). Most longitudinal tooth fractures (72.0%) occurred mainly in restored teeth, whereas only 28.0% were found in intact teeth. Compared with resin (4.7%) or porcelain (0.9%), the use of nonbonded inlay restoration materials such as gold (20.5%) or amalgam (18.7%) increased the occurrence of longitudinal tooth fractures. Out of 107 of longitudinal fractured teeth, 33 (30.8%) were treated endodontically and 74 (69.2%) were not. VRF was associated with endodontic treatment. The bite test is most reliable for reproducing symptoms. The combined use of various examination methods is recommended for detecting cracks and minutely inspecting all directions of a tooth. Copyright © 2012 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  11. Methylthioadenosine phosphorylase and activated insulin-like growth factor-1 receptor/insulin receptor: potential therapeutic targets in chordoma.

    Science.gov (United States)

    Sommer, Josh; Itani, Doha M; Homlar, Kelly C; Keedy, Vicki L; Halpern, Jennifer L; Holt, Ginger E; Schwartz, Herbert S; Coffin, Cheryl M; Kelley, Michael J; Cates, Justin M M

    2010-04-01

    Currently there is no effective chemotherapy for chordoma. Recent studies report co-expression of insulin-like growth factor-1 receptor (IGF1R) and its cognate ligand in chordoma, but it is unknown whether this receptor tyrosine kinase is activated in these tumours. Additionally, genetic studies have confirmed frequent deletions of chromosome 9p in chordomas, which encompasses the cyclin-dependent kinase inhibitor 2A (CDKN2A) locus. Another gene in this region, methylthioadenosine phosphorylase (MTAP), is an essential enzyme of the purine salvage pathway and has therapeutic relevance because MTAP-deficient cells are particularly sensitive to inhibitors of de novo purine synthesis. We investigated whether these pathways might be potential therapeutic targets for chordoma. Paraffin-embedded tissue samples from 30 chordomas were analysed by immunohistochemistry for expression of the phosphorylated isoforms of IGF1R or the insulin receptor (pIGF1R/pIR) and selected downstream signalling molecules, including BCL2-associated agonist of cell death protein (BAD). Expression of CDKN2A and MTAP proteins was also assessed. Skeletal chondrosarcomas, benign notochordal cell tumours, and fetal notochord were studied for comparison. Phosphorylated IGF1R/IR was detected in 41% of chordomas, together with activated downstream signalling molecules, and pIGF1R/pIR was absent in benign notochordal cell tumours and fetal notochord. Thirty-nine per cent of chordomas were negative for MTAP immunoreactivity. Patients with pIGF1R/pIR-positive tumours showed significantly decreased median disease-free survival in multivariate survival analysis (p = 0.036), whereas phosphorylation of BAD at serine-99 was found to be associated with a favourable prognosis (p = 0.002). Approximately 40% of chordomas demonstrate evidence of activation of the IGF1R/IR signalling pathway or loss of a key enzyme in the purine salvage pathway. Aberrant signalling cascades and disrupted metabolic pathways such as

  12. Partial Safety Factors and Target Reliability Level in Danish Structural Codes

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard; Hansen, J. O.; Nielsen, T. A.

    2001-01-01

    The partial safety factors in the newly revised Danish structural codes have been derived using a reliability-based calibration. The calibrated partial safety factors result in the same average reliability level as in the previous codes, but a much more uniform reliability level has been obtained...

  13. Pharmacological targeting of the KIT growth factor receptor: a therapeutic consideration for mast cell disorders

    DEFF Research Database (Denmark)

    Jensen, Bettina Margrethe; Akin, C; Gilfillan, A M

    2008-01-01

    KIT is a member of the tyrosine kinase family of growth factor receptors which is expressed on a variety of haematopoietic cells including mast cells. Stem cell factor (SCF)-dependent activation of KIT is critical for mast cell homeostasis and function. However, when KIT is inappropriately activa...

  14. Targeting and function of the mitochondrial fission factor GDAP1 are dependent on its tail-anchor.

    Directory of Open Access Journals (Sweden)

    Konstanze M Wagner

    Full Text Available Proteins controlling mitochondrial dynamics are often targeted to and anchored into the mitochondrial outer membrane (MOM by their carboxyl-terminal tail-anchor domain (TA. However, it is not known whether the TA modulates protein function. GDAP1 is a mitochondrial fission factor with two neighboring hydrophobic domains each flanked by basic amino acids (aa. Here we define GDAP1 as TA MOM protein. GDAP1 carries a single transmembrane domain (TMD that is, together with the adjacent basic aa, critical for MOM targeting. The flanking N-terminal region containing the other hydrophobic domain is located in the cytoplasm. TMD sequence, length, and high hydrophobicity do not influence GDAP1 fission function if MOM targeting is maintained. The basic aa bordering the TMD in the cytoplasm, however, are required for both targeting of GDAP1 as part of the TA and GDAP1-mediated fission. Thus, this GDAP1 region contains critical overlapping motifs defining intracellular targeting by the TA concomitant with functional aspects.

  15. The control of male fertility by spermatid-specific factors: searching for contraceptive targets from spermatozoon's head to tail.

    Science.gov (United States)

    Chen, Su-Ren; Batool, Aalia; Wang, Yu-Qian; Hao, Xiao-Xia; Chang, Chawn-Shang; Cheng, C Yan; Liu, Yi-Xun

    2016-11-10

    Male infertility due to abnormal spermatozoa has been reported in both animals and humans, but its pathogenic causes, including genetic abnormalities, remain largely unknown. On the other hand, contraceptive options for men are limited, and a specific, reversible and safe method of male contraception has been a long-standing quest in medicine. Some progress has recently been made in exploring the effects of spermatid-specifical genetic factors in controlling male fertility. A comprehensive search of PubMed for articles and reviews published in English before July 2016 was carried out using the search terms 'spermiogenesis failure', 'globozoospermia', 'spermatid-specific', 'acrosome', 'infertile', 'manchette', 'sperm connecting piece', 'sperm annulus', 'sperm ADAMs', 'flagellar abnormalities', 'sperm motility loss', 'sperm ion exchanger' and 'contraceptive targets'. Importantly, we have opted to focus on articles regarding spermatid-specific factors. Genetic studies to define the structure and physiology of sperm have shown that spermatozoa appear to be one of the most promising contraceptive targets. Here we summarize how these spermatid-specific factors regulate spermiogenesis and categorize them according to their localization and function from spermatid head to tail (e.g., acrosome, manchette, head-tail conjunction, annulus, principal piece of tail). In addition, we emphatically introduce small-molecule contraceptives, such as BRDT and PPP3CC/PPP3R2, which are currently being developed to target spermatogenic-specific proteins. We suggest that blocking the differentiation of haploid germ cells, which rarely affects early spermatogenic cell types and the testicular microenvironment, is a better choice than spermatogenic-specific proteins. The studies described here provide valuable information regarding the genetic and molecular defects causing male mouse infertility to improve our understanding of the importance of spermatid-specific factors in controlling

  16. Chimeric Monoclonal Antibody Cetuximab Targeting Epidermal Growth Factor-Receptor in Advanced Non-Melanoma Skin Cancer

    OpenAIRE

    Uwe Wollina; Georgi Tchernev; Torello Lotti

    2017-01-01

    BACKGROUND: Non-melanoma skin cancer (NMSC) is the most common malignancy in humans. Targeted therapy with monoclonal antibody cetuximab is an option in case of advanced tumor or metastasis. AIM: We present and update of the use of cetuximab in NMSC searching PUBMED 2011-2017. METHODS: The monoclonal antibody cetuximab against epidermal growth factor receptor (EGFR) has been investigated for its use in NMSC during the years 2011 to 2017 by a PUBMED research using the following items: ...

  17. The Populus ARBORKNOX1 homeodomain transcription factor regulates woody growth through binding to evolutionarily conserved target genes of diverse function.

    Science.gov (United States)

    Liu, Lijun; Zinkgraf, Matthew; Petzold, H Earl; Beers, Eric P; Filkov, Vladimir; Groover, Andrew

    2015-01-01

    The class I KNOX homeodomain transcription factor ARBORKNOX1 (ARK1) is a key regulator of vascular cambium maintenance and cell differentiation in Populus. Currently, basic information is lacking concerning the distribution, functional characteristics, and evolution of ARK1 binding in the Populus genome. Here, we used chromatin immunoprecipitation sequencing (ChIP-seq) technology to identify ARK1 binding loci genome-wide in Populus. Computational analyses evaluated the distribution of ARK1 binding loci, the function of genes associated with bound loci, the effect of ARK1 binding on transcript levels, and evolutionary conservation of ARK1 binding loci. ARK1 binds to thousands of loci which are highly enriched proximal to the transcriptional start sites of genes of diverse functions. ARK1 target genes are significantly enriched in paralogs derived from the whole-genome salicoid duplication event. Both ARK1 and a maize (Zea mays) homolog, KNOTTED1, preferentially target evolutionarily conserved genes. However, only a small portion of ARK1 target genes are significantly differentially expressed in an ARK1 over-expression mutant. This study describes the functional characteristics and evolution of DNA binding by a transcription factor in an undomesticated tree, revealing complexities similar to those shown for transcription factors in model animal species. No claim to original US Government works. New Phytologist © 2014 New Phytologist Trust.

  18. Ferulic Acid Exerts Anti-Angiogenic and Anti-Tumor Activity by Targeting Fibroblast Growth Factor Receptor 1-Mediated Angiogenesis.

    Science.gov (United States)

    Yang, Guang-Wei; Jiang, Jin-Song; Lu, Wei-Qin

    2015-10-12

    Most anti-angiogenic therapies currently being evaluated target the vascular endothelial growth factor (VEGF) pathway; however, the tumor vasculature can acquire resistance to VEGF-targeted therapy by shifting to other angiogenesis mechanisms. Therefore, other therapeutic agents that block non-VEGF angiogenic pathways need to be evaluated. Here, we identified ferulic acid as a novel fibroblast growth factor receptor 1 (FGFR1) inhibitor and a novel agent with potential anti-angiogenic and anti-cancer activities. Ferulic acid demonstrated inhibition of endothelial cell proliferation, migration and tube formation in response to basic fibroblast growth factor 1 (FGF1). In ex vivo and in vivo angiogenesis assays, ferulic acid suppressed FGF1-induced microvessel sprouting of rat aortic rings and angiogenesis. To understand the underlying molecular basis, we examined the effects of ferulic acid on different molecular components and found that ferulic acid suppressed FGF1-triggered activation of FGFR1 and phosphatidyl inositol 3-kinase (PI3K)-protein kinase B (Akt) signaling. Moreover, ferulic acid directly inhibited proliferation and blocked the PI3K-Akt pathway in melanoma cell. In vivo, using a melanoma xenograft model, ferulic acid showed growth-inhibitory activity associated with inhibition of angiogenesis. Taken together, our results indicate that ferulic acid targets the FGFR1-mediated PI3K-Akt signaling pathway, leading to the suppression of melanoma growth and angiogenesis.

  19. Bayesian multivariate meta-analysis of multiple factors.

    Science.gov (United States)

    Lin, Lifeng; Chu, Haitao

    2018-02-09

    In medical sciences, a disease condition is typically associated with multiple risk and protective factors. Although many studies report results of multiple factors, nearly all meta-analyses separately synthesize the association between each factor and the disease condition of interest. The collected studies usually report different subsets of factors, and the results from separate analyses on multiple factors may not be comparable because each analysis may use different subpopulation. This may impact on selecting most important factors to design a multifactor intervention program. This article proposes a new concept, multivariate meta-analysis of multiple factors (MVMA-MF), to synthesize all available factors simultaneously. By borrowing information across factors, MVMA-MF can improve statistical efficiency and reduce biases compared with separate analyses when factors were missing not at random. As within-study correlations between factors are commonly unavailable from published articles, we use a Bayesian hybrid model to perform MVMA-MF, which effectively accounts for both within- and between-study correlations. The performance of MVMA-MF and the conventional methods are compared using simulations and an application to a pterygium dataset consisting of 29 studies on 8 risk factors. Copyright © 2018 John Wiley & Sons, Ltd.

  20. Target identification in Fusobacterium nucleatum by subtractive genomics approach and enrichment analysis of host-pathogen protein-protein interactions.

    Science.gov (United States)

    Kumar, Amit; Thotakura, Pragna Lakshmi; Tiwary, Basant Kumar; Krishna, Ramadas

    2016-05-12

    Fusobacterium nucleatum, a well studied bacterium in periodontal diseases, appendicitis, gingivitis, osteomyelitis and pregnancy complications has recently gained attention due to its association with colorectal cancer (CRC) progression. Treatment with berberine was shown to reverse F. nucleatum-induced CRC progression in mice by balancing the growth of opportunistic pathogens in tumor microenvironment. Intestinal microbiota imbalance and the infections caused by F. nucleatum might be regulated by therapeutic intervention. Hence, we aimed to predict drug target proteins in F. nucleatum, through subtractive genomics approach and host-pathogen protein-protein interactions (HP-PPIs). We also carried out enrichment analysis of host interacting partners to hypothesize the possible mechanisms involved in CRC progression due to F. nucleatum. In subtractive genomics approach, the essential, virulence and resistance related proteins were retrieved from RefSeq proteome of F. nucleatum by searching against Database of Essential Genes (DEG), Virulence Factor Database (VFDB) and Antibiotic Resistance Gene-ANNOTation (ARG-ANNOT) tool respectively. A subsequent hierarchical screening to identify non-human homologous, metabolic pathway-independent/pathway-specific and druggable proteins resulted in eight pathway-independent and 27 pathway-specific druggable targets. Co-aggregation of F. nucleatum with host induces proinflammatory gene expression thereby potentiates tumorigenesis. Hence, proteins from IBDsite, a database for inflammatory bowel disease (IBD) research and those involved in colorectal adenocarcinoma as interpreted from The Cancer Genome Atlas (TCGA) were retrieved to predict drug targets based on HP-PPIs with F. nucleatum proteome. Prediction of HP-PPIs exhibited 186 interactions contributed by 103 host and 76 bacterial proteins. Bacterial interacting partners were accounted as putative targets. And enrichment analysis of host interacting partners showed statistically

  1. Targeting the epidermal growth factor receptor in solid tumors: focus on safety.

    Science.gov (United States)

    Lucchini, Eleonora; Pilotto, Sara; Spada, Elisa; Melisi, Davide; Bria, Emilio; Tortora, Giampaolo

    2014-05-01

    Inhibition of the EGFR has emerged as a promising anticancer strategy, offering improved efficacy and quality of life for patients affected by tumors. The overall level of toxicity associated with EGFR inhibitors is low compared to other chemotherapy drugs, although they are commonly associated with skin and gastrointestinal adverse events. Thus, patients' quality of life may be considerably affected both by a physical and a psychosocial perspective. Adverse events that lead to treatment interruption or cessation may significantly compromise their outcome. This review summarizes the characteristics of the distinctive toxicities of drugs targeting EGFR, addressing their incidence, pathophysiology and clinical presentation with a focus on the management of skin rash and other relevant adverse events, according to the available clinical evidence. Data regarding the correlation between the development of skin rash and clinical outcome are also reported. Drugs targeting EGFR are associated with a lower overall incidence of systemic side effects compared to standard chemotherapeutic agents; nevertheless, an increased risk of distinct toxicities that may affect patient's quality of life and anticancer treatment compliance is observed. Thus, clinical training projects directed toward a more accurate knowledge of such adverse events are essential to maximize the progress of targeted therapies against cancer.

  2. QTL replication and targeted association highlight the nerve growth factor gene for nonverbal communication deficits in autism spectrum disorders.

    Science.gov (United States)

    Lu, A T-H; Yoon, J; Geschwind, D H; Cantor, R M

    2013-02-01

    Autism Spectrum Disorder (ASD) has a heterogeneous etiology that is genetically complex. It is defined by deficits in communication and social skills and the presence of restricted and repetitive behaviors. Genetic analyses of heritable quantitative traits that correlate with ASD may reduce heterogeneity. With this in mind, deficits in nonverbal communication (NVC) were quantified based on items from the Autism Diagnostic Interview Revised. Our previous analysis of 228 families from the Autism Genetics Research Exchange (AGRE) repository reported 5 potential quantitative trait loci (QTL). Here we report an NVC QTL replication study in an independent sample of 213 AGRE families. One QTL was replicated (Panalysis of 476 haplotype blocks with 708 AGRE families using the Family Based Association Test (FBAT). Blocks in two QTL genes were associated with NVC with a P-value of 0.001. Three associated haplotype blocks were intronic to the Nerve Growth Factor (NGF) gene (P=0.001, 0.001, 0.002), and one was intronic to KCND3 (P=0.001). Individual haplotypes within the associated blocks drove the associations (0.003, 0.0004 and 0.0002) for NGF and 0.0001 for KCND3. Using the same methods, these genes were tested for association with NVC in an independent sample of 1517 families from an Autism Genome Project (AGP). NVC was associated with a haplotype in an adjacent NGF block (P=0.0005) and one 46 kb away from the associated block in KCND3 (0.008). These analyses illustrate the value of QTL and targeted association studies for genetically complex disorders such as ASD. NGF is a promising risk gene for NVC deficits.

  3. Examination of thromboxane synthase as a prognostic factor and therapeutic target in non-small cell lung cancer

    LENUS (Irish Health Repository)

    Cathcart, Mary-Clare

    2011-03-09

    Abstract Background Thromboxane synthase (TXS) metabolises prostaglandin H2 into thromboxanes, which are biologically active on cancer cells. TXS over-expression has been reported in a range of cancers, and associated with a poor prognosis. TXS inhibition induces cell death in-vitro, providing a rationale for therapeutic intervention. We aimed to determine the expression profile of TXS in NSCLC and if it is prognostic and\\/or a survival factor in the disease. Methods TXS expression was examined in human NSCLC and matched controls by western analysis and IHC. TXS metabolite (TXB2) levels were measured by EIA. A 204-patient NSCLC TMA was stained for COX-2 and downstream TXS expression. TXS tissue expression was correlated with clinical parameters, including overall survival. Cell proliferation\\/survival and invasion was examined in NSCLC cells following both selective TXS inhibition and stable TXS over-expression. Results TXS was over-expressed in human NSCLC samples, relative to matched normal controls. TXS and TXB2 levels were increased in protein (p < 0.05) and plasma (p < 0.01) NSCLC samples respectively. TXS tissue expression was higher in adenocarcinoma (p < 0.001) and female patients (p < 0.05). No significant correlation with patient survival was observed. Selective TXS inhibition significantly reduced tumour cell growth and increased apoptosis, while TXS over-expression stimulated cell proliferation and invasiveness, and was protective against apoptosis. Conclusion TXS is over-expressed in NSCLC, particularly in the adenocarcinoma subtype. Inhibition of this enzyme inhibits proliferation and induces apoptosis. Targeting thromboxane synthase alone, or in combination with conventional chemotherapy is a potential therapeutic strategy for NSCLC.

  4. Donor retention in health care in Iran: a factor analysis.

    Science.gov (United States)

    Aghababa, Sara; Nasiripour, Amir Ashkan; Maleki, Mohammadreza; Gohari, Mahmoodreza

    2017-01-01

    Background: Long-term financial support is essential for the survival of a charitable organization. Health charities need to identify the effective factors influencing donor retention. Methods: In the present study, the items of a questionnaire were derived from both literature review and semi-structured interviews related to donor retention. Using a purposive sampling, 300 academic and executive practitioners were selected. After the follow- up, a total of 243 usable questionnaires were prepared for factor analysis. The questionnaire was validated based on the face and content validity and reliability through Cronbach's α-coefficient. Results: The results of exploratory factor analysis extracted 2 factors for retention: donor factor (variance = 33.841%; Cronbach's α-coefficient = 90.2) and charity factor (variance = 29.038%; Cronbach's α-coefficient = 82.8), respectively. Subsequently, confirmatory factor analysis was applied to support the overall reasonable fit. Conclusions: In this study, it was found that repeated monetary donations are supplied to the charitable organizations when both aspects of donor factor (retention factor and charity factor) for retention are taken into consideration. This model could provide a perspective for making sustainable donations and charitable giving.

  5. Virtual diplomacy: an analysis of the structure of the target audiences

    Directory of Open Access Journals (Sweden)

    V. V. Verbytska

    2016-03-01

    Full Text Available In the context of the global information society the communication processes, especially at the international level, become more important.  The effectiveness of communication depends primarily on its focus, i.e. on defining clearly the target audience which it should focus on. Virtual diplomacy, as a kind of political communication at the international level, is no exception.  The novelty, rapid development and dissemination of this phenomenon require profound analysis and elaboration of effective utilization strategies, including studying its recipients and target audiences. Purpose: identification, structuring and analysis of the recipients of virtual diplomacy as the audiences of international political communication. The study uses such research methods, as system analysis, structural functionalism, dialectics and synergy, comparison, critical analysis. Main results of the research: 1. The study examined the specifics of political communication in the context of the development of the global information society at the international level. 2. It also analyzed the recipients of virtual diplomacy as a kind of political communication at the international level. 3. The study highlighted the key target groups in the global Internet network based on the tasks performed by virtual diplomacy. 4. It proved the effectiveness of cooperation with each target group in the framework of virtual diplomacy. 5. It described the specifics of the work with each target group in the context of virtual diplomacy. Practical implications: The article may be useful for writing scientific theoretical studies, tests, essays and term papers, for designing special courses in universities in the sphere of international relations and international information. It can also be a guide for the authorities carrying out diplomatic activities and international information cooperation. Findings: In the context of the establishment of the global information society political

  6. System for automatic x-ray-image analysis, measurement, and sorting of laser fusion targets

    International Nuclear Information System (INIS)

    Singleton, R.M.; Perkins, D.E.; Willenborg, D.L.

    1980-01-01

    This paper describes the Automatic X-Ray Image Analysis and Sorting (AXIAS) system which is designed to analyze and measure x-ray images of opaque hollow microspheres used as laser fusion targets. The x-ray images are first recorded on a high resolution film plate. The AXIAS system then digitizes and processes the images to accurately measure the target parameters and defects. The primary goals of the AXIAS system are: to provide extremely accurate and rapid measurements, to engineer a practical system for a routine production environment and to furnish the capability of automatically measuring an array of images for sorting and selection

  7. Hot-spot analysis for drug discovery targeting protein-protein interactions.

    Science.gov (United States)

    Rosell, Mireia; Fernández-Recio, Juan

    2018-04-01

    Protein-protein interactions are important for biological processes and pathological situations, and are attractive targets for drug discovery. However, rational drug design targeting protein-protein interactions is still highly challenging. Hot-spot residues are seen as the best option to target such interactions, but their identification requires detailed structural and energetic characterization, which is only available for a tiny fraction of protein interactions. Areas covered: In this review, the authors cover a variety of computational methods that have been reported for the energetic analysis of protein-protein interfaces in search of hot-spots, and the structural modeling of protein-protein complexes by docking. This can help to rationalize the discovery of small-molecule inhibitors of protein-protein interfaces of therapeutic interest. Computational analysis and docking can help to locate the interface, molecular dynamics can be used to find suitable cavities, and hot-spot predictions can focus the search for inhibitors of protein-protein interactions. Expert opinion: A major difficulty for applying rational drug design methods to protein-protein interactions is that in the majority of cases the complex structure is not available. Fortunately, computational docking can complement experimental data. An interesting aspect to explore in the future is the integration of these strategies for targeting PPIs with large-scale mutational analysis.

  8. An analysis of health promotion materials for Dutch truck drivers: Off target and too complex?

    Science.gov (United States)

    Boeijinga, Anniek; Hoeken, Hans; Sanders, José

    2017-01-01

    Despite various health promotion initiatives, unfavorable figures regarding Dutch truck drivers' eating behaviors, exercise behaviors, and absenteeism have not improved. The aim was to obtain a better understanding of the low level of effectiveness of current health interventions for Dutch truck drivers by examining to what extent these are tailored to the target group's particular mindset (focus of content) and health literacy skills (presentation of content). The article analyzes 21 health promotion materials for Dutch truck drivers using a two-step approach: (a) an analysis of the materials' focus, guided by the Health Action Process Approach; and (b) an argumentation analysis, guided by pragma-dialectics. The corpus analysis revealed: (a) a predominant focus on the motivation phase; and (b) in line with the aim of motivating the target group, a consistent use of pragmatic arguments, which were typically presented in an implicit way. The results indicate that existing health promotion materials for Dutch truck drivers are not sufficiently tailored to the target group's mindset and health literacy skills. Recommendations are offered to develop more tailored/effective health interventions targeting this high-risk, underserved occupational group.

  9. TargetVue: Visual Analysis of Anomalous User Behaviors in Online Communication Systems.

    Science.gov (United States)

    Cao, Nan; Shi, Conglei; Lin, Sabrina; Lu, Jie; Lin, Yu-Ru; Lin, Ching-Yung

    2016-01-01

    Users with anomalous behaviors in online communication systems (e.g. email and social medial platforms) are potential threats to society. Automated anomaly detection based on advanced machine learning techniques has been developed to combat this issue; challenges remain, though, due to the difficulty of obtaining proper ground truth for model training and evaluation. Therefore, substantial human judgment on the automated analysis results is often required to better adjust the performance of anomaly detection. Unfortunately, techniques that allow users to understand the analysis results more efficiently, to make a confident judgment about anomalies, and to explore data in their context, are still lacking. In this paper, we propose a novel visual analysis system, TargetVue, which detects anomalous users via an unsupervised learning model and visualizes the behaviors of suspicious users in behavior-rich context through novel visualization designs and multiple coordinated contextual views. Particularly, TargetVue incorporates three new ego-centric glyphs to visually summarize a user's behaviors which effectively present the user's communication activities, features, and social interactions. An efficient layout method is proposed to place these glyphs on a triangle grid, which captures similarities among users and facilitates comparisons of behaviors of different users. We demonstrate the power of TargetVue through its application in a social bot detection challenge using Twitter data, a case study based on email records, and an interview with expert users. Our evaluation shows that TargetVue is beneficial to the detection of users with anomalous communication behaviors.

  10. Bioinformatic identification and expression analysis of banana microRNAs and their targets.

    Science.gov (United States)

    Chai, Juan; Feng, Renjun; Shi, Hourui; Ren, Mengyun; Zhang, Yindong; Wang, Jingyi

    2015-01-01

    MicroRNAs (miRNAs) represent a class of endogenous non-coding small RNAs that play important roles in multiple biological processes by degrading targeted mRNAs or repressing mRNA translation. Thousands of miRNAs have been identified in many plant species, whereas only a limited number of miRNAs have been predicted in M. acuminata (A genome) and M. balbisiana (B genome). Here, previously known plant miRNAs were BLASTed against the Expressed Sequence Tag (EST) and Genomic Survey Sequence (GSS), a database of banana genes. A total of 32 potential miRNAs belonging to 13 miRNAs families were detected using a range of filtering criteria. 244 miRNA:target pairs were subsequently predicted, most of which encode transcription factors or enzymes that participate in the regulation of development, growth, metabolism, and other physiological processes. In order to validate the predicted miRNAs and the mutual relationship between miRNAs and their target genes, qRT-PCR was applied to detect the tissue-specific expression levels of 12 putative miRNAs and 6 target genes in roots, leaves, flowers, and fruits. This study provides some important information about banana pre-miRNAs, mature miRNAs, and miRNA target genes and these findings can be applied to future research of miRNA functions.

  11. Bioinformatic identification and expression analysis of banana microRNAs and their targets.

    Directory of Open Access Journals (Sweden)

    Juan Chai

    Full Text Available MicroRNAs (miRNAs represent a class of endogenous non-coding small RNAs that play important roles in multiple biological processes by degrading targeted mRNAs or repressing mRNA translation. Thousands of miRNAs have been identified in many plant species, whereas only a limited number of miRNAs have been predicted in M. acuminata (A genome and M. balbisiana (B genome. Here, previously known plant miRNAs were BLASTed against the Expressed Sequence Tag (EST and Genomic Survey Sequence (GSS, a database of banana genes. A total of 32 potential miRNAs belonging to 13 miRNAs families were detected using a range of filtering criteria. 244 miRNA:target pairs were subsequently predicted, most of which encode transcription factors or enzymes that participate in the regulation of development, growth, metabolism, and other physiological processes. In order to validate the predicted miRNAs and the mutual relationship between miRNAs and their target genes, qRT-PCR was applied to detect the tissue-specific expression levels of 12 putative miRNAs and 6 target genes in roots, leaves, flowers, and fruits. This study provides some important information about banana pre-miRNAs, mature miRNAs, and miRNA target genes and these findings can be applied to future research of miRNA functions.

  12. Design Analysis of SNS Target StationBiological Shielding Monoligh with Proton Power Uprate

    Energy Technology Data Exchange (ETDEWEB)

    Bekar, Kursat B. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Ibrahim, Ahmad M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2017-05-01

    This report documents the analysis of the dose rate in the experiment area outside the Spallation Neutron Source (SNS) target station shielding monolith with proton beam energy of 1.3 GeV. The analysis implemented a coupled three dimensional (3D)/two dimensional (2D) approach that used both the Monte Carlo N-Particle Extended (MCNPX) 3D Monte Carlo code and the Discrete Ordinates Transport (DORT) two dimensional deterministic code. The analysis with proton beam energy of 1.3 GeV showed that the dose rate in continuously occupied areas on the lateral surface outside the SNS target station shielding monolith is less than 0.25 mrem/h, which complies with the SNS facility design objective. However, the methods and codes used in this analysis are out of date and unsupported, and the 2D approximation of the target shielding monolith does not accurately represent the geometry. We recommend that this analysis is updated with modern codes and libraries such as ADVANTG or SHIFT. These codes have demonstrated very high efficiency in performing full 3D radiation shielding analyses of similar and even more difficult problems.

  13. An analysis of the dependence of saccadic latency on target position and target characteristics in human subjects

    Directory of Open Access Journals (Sweden)

    Rosenberg Jay R

    2001-09-01

    Full Text Available Abstract Background Predictions from conduction velocity data for primate retinal ganglion cell axons indicate that the conduction time to the lateral geniculate nucleus for stimulation of peripheral retina should be no longer than for stimulation of central retina. On this basis, the latency of saccadic eye movements should not increase for more peripherally located targets. However, previous studies have reported relatively very large increases, which has the implication of a very considerable increase in central processing time for the saccade-generating system. Results In order to resolve this paradox, we have undertaken an extended series of experiments in which saccadic eye movements were recorded by electro-oculography in response to targets presented in the horizontal meridian in normal young subjects. For stationary or moving targets of either normal beam intensity or reduced red intensity, with the direction of gaze either straight ahead with respect to the head or directed eccentrically, the saccadic latency was shown to remain invariant with respect to a wide range of target angular displacements. Conclusions These results indicate that, irrespective of the angular displacement of the target, the direction of gaze or the target intensity, the saccade-generating system operates with a constant generation time.

  14. Problems with EM Algorithms for ML Factor Analysis.

    Science.gov (United States)

    Bentler, P. M.; Tanaka, Jeffrey S.

    1983-01-01

    Rubin and Thayer recently presented equations to implement maximum likelihood estimation in factor analysis via the EM algorithm. It is argued here that the advantages of using the EM algorithm remain to be demonstrated. (Author/JKS)

  15. Platelet-Derived Growth Factor (PDGF/PDGF Receptors (PDGFR Axis as Target for Antitumor and Antiangiogenic Therapy

    Directory of Open Access Journals (Sweden)

    Anca Maria Cimpean

    2010-03-01

    Full Text Available Angiogenesis in normal and pathological conditions is a multi-step process governed by positive and negative endogenous regulators. Many growth factors are involved in different steps of angiogenesis, like vascular endothelial growth factors (VEGF, fibroblast growth factor (FGF-2 or platelet-derived growth factors (PDGF. From these, VEGF and FGF-2 were extensively investigated and it was shown that they significantly contribute to the induction and progression of angiogenesis. A lot of evidence has been accumulated in last 10 years that supports the contribution of PDGF/PDGFR axis in developing angiogenesis in both normal and tumoral conditions. The crucial role of PDGF-B and PDGFR-β in angiogenesis has been demonstrated by gene targeting experiments, and their expression correlates with increased vascularity and maturation of the vascular wall. PDGF and their receptors were identified in a large variety of human tumor cells. In experimental models it was shown that inhibition of PDGF reduces interstitial fluid pressure in tumors and enhances the effect of chemotherapy. PDGFR have been involved in the cardiovascular development and their loss leads to a disruption in yolk sac blood vessels development. PDGFRβ expression by pericytes is necessary for their recruitment and integration in the wall of tumor vessels. Endothelial cells of tumor-associated blood vessels can express PDGFR. Based on these data, it was suggested the potential benefit of targeting PDGFR in the treatment of solid tumors. The molecular mechanisms of PDGF/PDGFR-mediated angiogenesis are not fully understood, but it was shown that tyrosine kinase inhibitors reduce tumor growth and angiogenesis in experimental xenograft models, and recent data demonstrated their efficacy in chemoresistant tumors. The in vivo effects of PDGFR inhibitors are more complex, based on the cross-talk with other angiogenic factors. In this review, we summarize data regarding the mechanisms and

  16. Text mining factor analysis (TFA) in green tea patent data

    Science.gov (United States)

    Rahmawati, Sela; Suprijadi, Jadi; Zulhanif

    2017-03-01

    Factor analysis has become one of the most widely used multivariate statistical procedures in applied research endeavors across a multitude of domains. There are two main types of analyses based on factor analysis: Exploratory Factor Analysis (EFA) and Confirmatory Factor Analysis (CFA). Both EFA and CFA aim to observed relationships among a group of indicators with a latent variable, but they differ fundamentally, a priori and restrictions made to the factor model. This method will be applied to patent data technology sector green tea to determine the development technology of green tea in the world. Patent analysis is useful in identifying the future technological trends in a specific field of technology. Database patent are obtained from agency European Patent Organization (EPO). In this paper, CFA model will be applied to the nominal data, which obtain from the presence absence matrix. While doing processing, analysis CFA for nominal data analysis was based on Tetrachoric matrix. Meanwhile, EFA model will be applied on a title from sector technology dominant. Title will be pre-processing first using text mining analysis.

  17. Developmental Coordination Disorder: Validation of a Qualitative Analysis Using Statistical Factor Analysis

    OpenAIRE

    Kathy Ahern

    2002-01-01

    This study investigates triangulation of the findings of a qualitative analysis by applying an exploratory factor analysis to themes identified in a phenomenological study. A questionnaire was developed from a phenomenological analysis of parents' experiences of parenting a child with Developmental Coordination Disorder (DCD). The questionnaire was administered to 114 parents of DCD children and data were analyzed using an exploratory factor analysis. The extracted factors provided support fo...

  18. Establishing Evidence for Internal Structure Using Exploratory Factor Analysis

    Science.gov (United States)

    Watson, Joshua C.

    2017-01-01

    Exploratory factor analysis (EFA) is a data reduction technique used to condense data into smaller sets of summary variables by identifying underlying factors potentially accounting for patterns of collinearity among said variables. Using an illustrative example, the 5 general steps of EFA are described with best practices for decision making…

  19. CFD Analysis of the Active Part of the HYPER Spallation Target

    International Nuclear Information System (INIS)

    Nam-il Tak; Chungho Cho; Tae-Yung Song

    2006-01-01

    KAERI (Korea Atomic Energy Research Institute) is developing an accelerator driven system (ADS) named HYPER (HYbrid Power Extraction Reactor) for a transmutation of long-lived nuclear wastes. One of the challenging tasks for the HYPER system is to design a large spallation target having a beam power of 15∼25 MW. The present paper focuses on the thermal-hydraulic performance of the active part of the HYPER target. Computational fluid dynamics (CFD) analysis was performed using a commercial code CFX 5.7.1. Several advanced turbulence models with different grid structures were applied. The CFX results show the significant impact of the turbulence model on the window temperature. It is concluded that experimental verifications are very important for the design of the HYPER target. (authors)

  20. Mapping Long Noncoding RNA Chromatin Occupancy Using Capture Hybridization Analysis of RNA Targets (CHART).

    Science.gov (United States)

    Vance, Keith W

    2017-01-01

    Capture Hybridization Analysis of RNA Targets (CHART) has recently been developed to map the genome-wide binding profile of chromatin-associated RNAs. This protocol uses a small number of 22-28 nucleotide biotinylated antisense oligonucleotides, complementary to regions of the target RNA that are accessible for hybridization, to purify RNAs from a cross-linked chromatin extract. RNA-chromatin complexes are next immobilized on beads, washed, and specifically eluted using RNase H. Associated genomic DNA is then sequenced using high-throughput sequencing technologies and mapped to the genome to identify RNA-chromatin associations on a large scale. CHART-based strategies can be applied to determine the nature and extent of long noncoding RNA (long ncRNA) association with chromatin genome-wide and identify direct long ncRNA transcriptional targets.

  1. Efficacy of epidermal growth factor receptor targeting in advanced chordoma: case report and literature review.

    Science.gov (United States)

    Launay, Simon G; Chetaille, Bruno; Medina, Fanny; Perrot, Delphine; Nazarian, Serge; Guiramand, Jérôme; Moureau-Zabotto, Laurence; Bertucci, François

    2011-10-04

    Chordomas are very rare low-grade malignant bone tumors that arise from the embryonic rests of the notochord. They are characterized by slow growth and long history with frequent local relapses, and sometimes metastases. While chemotherapy is not efficient, imatinib has shown antitumor activity. We report on a 76-year-old patient with EGFR-overexpressing advanced chordoma that progressed on imatinib and subsequently responded to erlotinib during 12 months. We report the fourth case of advanced chordoma treated with an EGFR inhibitor. We also review the literature concerning the rationale and potential of EGFR targeting in chordoma.

  2. Efficacy of epidermal growth factor receptor targeting in advanced chordoma: case report and literature review

    Directory of Open Access Journals (Sweden)

    Guiramand Jérôme

    2011-10-01

    Full Text Available Abstract Background Chordomas are very rare low-grade malignant bone tumors that arise from the embryonic rests of the notochord. They are characterized by slow growth and long history with frequent local relapses, and sometimes metastases. While chemotherapy is not efficient, imatinib has shown antitumor activity. Case presentation We report on a 76-year-old patient with EGFR-overexpressing advanced chordoma that progressed on imatinib and subsequently responded to erlotinib during 12 months. Conclusions We report the fourth case of advanced chordoma treated with an EGFR inhibitor. We also review the literature concerning the rationale and potential of EGFR targeting in chordoma.

  3. Strategies for enhancing the implementation of school-based policies or practices targeting risk factors for chronic disease.

    Science.gov (United States)

    Wolfenden, Luke; Nathan, Nicole K; Sutherland, Rachel; Yoong, Sze Lin; Hodder, Rebecca K; Wyse, Rebecca J; Delaney, Tessa; Grady, Alice; Fielding, Alison; Tzelepis, Flora; Clinton-McHarg, Tara; Parmenter, Benjamin; Butler, Peter; Wiggers, John; Bauman, Adrian; Milat, Andrew; Booth, Debbie; Williams, Christopher M

    2017-11-29

    consulted with experts in the field to identify other relevant research. 'Implementation' was defined as the use of strategies to adopt and integrate evidence-based health interventions and to change practice patterns within specific settings. We included any trial (randomised or non-randomised) conducted at any scale, with a parallel control group that compared a strategy to implement policies or practices to address diet, physical activity, overweight or obesity, tobacco or alcohol use by school staff to 'no intervention', 'usual' practice or a different implementation strategy. Citation screening, data extraction and assessment of risk of bias was performed by review authors in pairs. Disagreements between review authors were resolved via consensus, or if required, by a third author. Considerable trial heterogeneity precluded meta-analysis. We narratively synthesised trial findings by describing the effect size of the primary outcome measure for policy or practice implementation (or the median of such measures where a single primary outcome was not stated). We included 27 trials, 18 of which were conducted in the USA. Nineteen studies employed randomised controlled trial (RCT) designs. Fifteen trials tested strategies to implement healthy eating policies, practice or programs; six trials tested strategies targeting physical activity policies or practices; and three trials targeted tobacco policies or practices. Three trials targeted a combination of risk factors. None of the included trials sought to increase the implementation of interventions to delay initiation or reduce the consumption of alcohol. All trials examined multi-strategic implementation strategies and no two trials examined the same combinations of implementation strategies. The most common implementation strategies included educational materials, educational outreach and educational meetings. For all outcomes, the overall quality of evidence was very low and the risk of bias was high for the majority of

  4. Left ventricular wall motion abnormalities evaluated by factor analysis as compared with Fourier analysis

    International Nuclear Information System (INIS)

    Hirota, Kazuyoshi; Ikuno, Yoshiyasu; Nishikimi, Toshio

    1986-01-01

    Factor analysis was applied to multigated cardiac pool scintigraphy to evaluate its ability to detect left ventricular wall motion abnormalities in 35 patients with old myocardial infarction (MI), and in 12 control cases with normal left ventriculography. All cases were also evaluated by conventional Fourier analysis. In most cases with normal left ventriculography, the ventricular and atrial factors were extracted by factor analysis. In cases with MI, the third factor was obtained in the left ventricle corresponding to wall motion abnormality. Each case was scored according to the coincidence of findings of ventriculography and those of factor analysis or Fourier analysis. Scores were recorded for three items; the existence, location, and degree of asynergy. In cases of MI, the detection rate of asynergy was 94 % by factor analysis, 83 % by Fourier analysis, and the agreement in respect to location was 71 % and 66 %, respectively. Factor analysis had higher scores than Fourier analysis, but this was not significant. The interobserver error of factor analysis was less than that of Fourier analysis. Factor analysis can display locations and dynamic motion curves of asynergy, and it is regarded as a useful method for detecting and evaluating left ventricular wall motion abnormalities. (author)

  5. iTAR: a web server for identifying target genes of transcription factors using ChIP-seq or ChIP-chip data.

    Science.gov (United States)

    Yang, Chia-Chun; Andrews, Erik H; Chen, Min-Hsuan; Wang, Wan-Yu; Chen, Jeremy J W; Gerstein, Mark; Liu, Chun-Chi; Cheng, Chao

    2016-08-12

    Chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP-seq) or microarray hybridization (ChIP-chip) has been widely used to determine the genomic occupation of transcription factors (TFs). We have previously developed a probabilistic method, called TIP (Target Identification from Profiles), to identify TF target genes using ChIP-seq/ChIP-chip data. To achieve high specificity, TIP applies a conservative method to estimate significance of target genes, with the trade-off being a relatively low sensitivity of target gene identification compared to other methods. Additionally, TIP's output does not render binding-peak locations or intensity, information highly useful for visualization and general experimental biological use, while the variability of ChIP-seq/ChIP-chip file formats has made input into TIP more difficult than desired. To improve upon these facets, here we present are fined TIP with key extensions. First, it implements a Gaussian mixture model for p-value estimation, increasing target gene identification sensitivity and more accurately capturing the shape of TF binding profile distributions. Second, it enables the incorporation of TF binding-peak data by identifying their locations in significant target gene promoter regions and quantifies their strengths. Finally, for full ease of implementation we have incorporated it into a web server ( http://syslab3.nchu.edu.tw/iTAR/ ) that enables flexibility of input file format, can be used across multiple species and genome assembly versions, and is freely available for public use. The web server additionally performs GO enrichment analysis for the identified target genes to reveal the potential function of the corresponding TF. The iTAR web server provides a user-friendly interface and supports target gene identification in seven species, ranging from yeast to human. To facilitate investigating the quality of ChIP-seq/ChIP-chip data, the web server generates the chart of the

  6. A resource for characterizing genome-wide binding and putative target genes of transcription factors expressed during secondary growth and wood formation in Populus

    Science.gov (United States)

    Lijun Liu; Trevor Ramsay; Matthew S. Zinkgraf; David Sundell; Nathaniel Robert Street; Vladimir Filkov; Andrew Groover

    2015-01-01

    Identifying transcription factor target genes is essential for modeling the transcriptional networks underlying developmental processes. Here we report a chromatin immunoprecipitation sequencing (ChIP-seq) resource consisting of genome-wide binding regions and associated putative target genes for four Populus homeodomain transcription factors...

  7. Seismic analysis of fuel and target assemblies at a production reactor

    International Nuclear Information System (INIS)

    Braverman, J.I.; Wang, Y.K.

    1991-01-01

    This paper describes the unique modeling and analysis considerations used to assess the seismic adequacy of the fuel and target assemblies in a production reactor at Savannah River Site. This confirmatory analysis was necessary to provide assurance that the reactor can operate safely during a seismic event and be brought to a safe shutdown condition. The plant which was originally designed in the 1950's required to be assessed to more current seismic criteria. The design of the reactor internals and the magnitude of the structural responses enabled the use of a linear elastic dynamic analysis. A seismic analysis was performed using a finite element model consisting of the fuel and target assemblies, reactor tank, and a portion of the concrete structure supporting the reactor tank. The effects of submergence of the fuel and target assemblies in the water contained within the reactor tank can have a significant effect on their seismic response. Thus, the model included hydrodynamic fluid coupling effects between the assemblies and the reactor tank. Fluid coupling mass terms were based on formulations for solid bodies immersed in incompressible and frictionless fluids. The potential effects of gap conditions were also assessed in this evaluation. 5 refs., 6 figs., 1 tab

  8. Four-dimensional targeting error analysis in image-guided radiotherapy

    International Nuclear Information System (INIS)

    Riboldi, M; Baroni, G; Sharp, G C; Chen, G T Y

    2009-01-01

    Image-guided therapy (IGT) involves acquisition and processing of biomedical images to actively guide medical interventions. The proliferation of IGT technologies has been particularly significant in image-guided radiotherapy (IGRT), as a way to increase the tumor targeting accuracy. When IGRT is applied to moving tumors, image guidance becomes challenging, as motion leads to increased uncertainty. Different strategies may be applied to mitigate the effects of motion: each technique is related to a different technological effort and complexity in treatment planning and delivery. The objective comparison of different motion mitigation strategies can be achieved by quantifying the residual uncertainties in tumor targeting, to be detected by means of IGRT technologies. Such quantification requires an extension of targeting error theory to a 4D space, where the 3D tumor trajectory as a function of time measured (4D Targeting Error, 4DTE). Accurate 4DTE analysis can be represented by a motion probability density function, describing the statistical fluctuations of tumor trajectory. We illustrate the application of 4DTE analysis through examples, including weekly variations in tumor trajectory as detected by 4DCT, respiratory gating via external surrogates and real-time tumor tracking.

  9. Analysis of the thermomechanical behavior of the IFMIF bayonet target assembly under design loading scenarios

    Energy Technology Data Exchange (ETDEWEB)

    Bernardi, D., E-mail: davide.bernardi@enea.it [ENEA Brasimone, Camugnano, BO (Italy); Arena, P.; Bongiovì, G.; Di Maio, P.A. [Dipartimento di Energia, Ingegneria dell’Informazione e Modelli Matematici, Università di Palermo, Viale delle Scienze, Palermo (Italy); Frisoni, M. [ENEA Bologna, Via Martiri di Monte Sole 4, Bologna (Italy); Miccichè, G.; Serra, M. [ENEA Brasimone, Camugnano, BO (Italy)

    2015-10-15

    In the framework of the IFMIF Engineering Validation and Engineering Design Activities (IFMIF/EVEDA) phase, ENEA is responsible for the design of the European concept of the IFMIF lithium target system which foresees the possibility to periodically replace only the most irradiated and thus critical component (i.e., the backplate) while continuing to operate the rest of the target for a longer period (the so-called bayonet backplate concept). In this work, the results of the steady state thermomechanical analysis of the IFMIF bayonet target assembly under two different design loading scenarios (a “hot” scenario and a “cold” scenario) are briefly reported highlighting the relevant indications obtained with respect to the fulfillment of the design requirements. In particular, the analyses have shown that in the hot scenario the temperatures reached in the target assembly are within the material acceptable limits while in the cold scenario transition below the ductile to brittle transition temperature (DBTT) cannot be excluded. Moreover, results indicate that the contact between backplate and high flux test module is avoided and that the overall structural integrity of the system is assured in both scenarios. However, stress linearization analysis reveals that ITER Structural Design Criteria for In-vessel Components (SDC-IC) design rules are not always met along the selected paths at backplate middle plane section in the hot scenario, thus suggesting the need of a revision of the backplate design or a change of the operating conditions.

  10. Epidermal growth factor receptor is a preferred target for treating Amyloid-β–induced memory loss

    OpenAIRE

    Wang, Lei; Chiang, Hsueh-Cheng; Wu, Wenjuan; Liang, Bin; Xie, Zuolei; Yao, Xinsheng; Ma, Weiwei; Du, Shuwen; Zhong, Yi

    2012-01-01

    Current understanding of amyloid-β (Aβ) metabolism and toxicity provides an extensive list of potential targets for developing drugs for treating Alzheimer’s disease. We took two independent approaches, including synaptic-plasticity–based analysis and behavioral screening of synthetic compounds, for identifying single compounds that are capable of rescuing the Aβ-induced memory loss in both transgenic fruit fly and transgenic mouse models. Two clinically available drugs and three synthetic co...

  11. Hierarchical axon targeting of Drosophila olfactory receptor neurons specified by the proneural transcription factors Atonal and Amos.

    Science.gov (United States)

    Okumura, Misako; Kato, Tomoko; Miura, Masayuki; Chihara, Takahiro

    2016-01-01

    Sensory information is spatially represented in the brain to form a neural map. It has been suggested that axon-axon interactions are important for neural map formation; however, the underlying mechanisms are not fully understood. We used the Drosophila antennal lobe, the first olfactory center in the brain, as a model for studying neural map formation. Olfactory receptor neurons (ORNs) expressing the same odorant receptor target their axons to a single glomerulus out of approximately 50 glomeruli in the antennal lobe. Previous studies have showed that the axons of Atonal ORNs, specified by Atonal, a basic helix-loop-helix (bHLH) transcription factor, pioneer antennal lobe formation; however, the details remain to be elucidated. Here, we show that genetic ablation of Atonal ORNs affects antennal lobe structure and axon targeting of Amos ORNs, another type of ORN specified by the bHLH transcription factor Amos. During development, Atonal ORNs reach the antennal lobe and form the axon commissure before Amos ORNs. We also found that N-cadherin knockdown specifically in Atonal ORNs disrupts the glomerular boundary in the whole antennal lobe. Our results suggest that Atonal ORNs function as pioneer axons. Thus, correct axon targeting of Atonal ORNs is essential for formation of the whole antennal lobe. © 2015 The Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd.

  12. Targets in the microenvironment of rectal cancer : A focus on angiogenic growth factors and chemokines

    NARCIS (Netherlands)

    Tamas, Karin Rita

    2015-01-01

    Cancer cells interact with each other, and with cells of the tumor microenvironment. This coincides with the production of numerous soluble factors which can stimulate cancer cell growth and migration. In addition the tumor microenvironment can facilitate cancer cells to escape the effect of

  13. B-cell activating factor in the pathophysiology of multiple myeloma: a target for therapy?

    NARCIS (Netherlands)

    Hengeveld, P. J.; Kersten, M. J.

    2015-01-01

    Multiple myeloma (MM) is a currently incurable malignancy of plasma cells. Malignant myeloma cells (MMCs) are heavily dependent upon the bone marrow (BM) microenvironment for their survival. One component of this tumor microenvironment, B-Cell Activating Factor (BAFF), has been implicated as a key

  14. Anxiety sensitivity and working memory capacity: Risk factors and targets for health behavior promotion

    NARCIS (Netherlands)

    Otto, M.W.; Eastman, A.; Lo, S.; Hearon, B.A.; Bickel, W.K.; Zvolensky, M.J.; Smits, J.A.J.; Doan, S.N.

    2016-01-01

    Understanding the nature and influence of specific risk profiles is increasingly important for health behavior promotion. The purpose of this article is to document the value of two factors - anxiety sensitivity (AS) and working memory capacity (WMC) - for enhancing risk for the initiation and/or

  15. Preclinical evaluation of radiolabelled nimotuzumab, a promising monoclonal antibody targeting the epidermal growth factor receptor

    Czech Academy of Sciences Publication Activity Database

    Bárta, P.; Lázníčková, A.; Lázníček, M.; Beckford, Denis R.; Beran, Miloš

    2013-01-01

    Roč. 56, č. 5 (2013), s. 280-288 ISSN 0362-4803 Grant - others:GA ČR(CZ) GAP304/10/1738 Institutional support: RVO:61389005 Keywords : radiopharmaceutical * 177Lu * 131I * nimotuzumab * EGFR * preclinical biodistribution Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 1.187, year: 2013

  16. Targeting cleavage and polyadenylation specific factor 1 via shRNA ...

    Indian Academy of Sciences (India)

    Cleavage and polyadenylation specificity factor 1 (CPSF1), a member of CPSF complex, has been reported to play a keyrole in pre-mRNA 30-end formation, but its possible role in ovarian cancer remains unclear. In the present study, we foundthe mRNA level of CPSF1 was overexpressed in ovarian cancer tissues using ...

  17. Efficacy of Cognitive-Behavioral Interventions Targeting Personality Risk Factors for Youth Alcohol Misuse

    Science.gov (United States)

    Conrod, Patricia J.; Stewart, Sherry H.; Comeau, Nancy; Maclean, A. Michael

    2006-01-01

    Sensation seeking, anxiety sensitivity, and hopelessness are personality risk factors for alcohol use disorders, each associated with specific risky drinking motives in adolescents. We developed a set of interventions and manuals that were designed to intervene at the level of personality risk and associated maladaptive coping strategies,…

  18. Roles of the Nfu Fe–S targeting factors in the trypanosome mitochondrion

    Czech Academy of Sciences Publication Activity Database

    Benz, C.; Kovářová, Julie; Králová-Hromadová, Ivica; Pierik, A. J.; Lukeš, Julius

    2016-01-01

    Roč. 46, č. 10 (2016), s. 641-651 ISSN 0020-7519 EU Projects: European Commission(XE) 316304 - MODBIOLIN Institutional support: RVO:60077344 Keywords : Trypanosoma brucei * Nfu1 * iron–sulphur cluster * Fe–S Mitochondrion Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.730, year: 2016

  19. Transcription factors as targets for improving Aspergillus niger as cell factory

    DEFF Research Database (Denmark)

    Poulsen, Lars; Bruno, K.S.; Thykær, Jette

    ). In the present study the effect of modulation of transcription factors in Aspergillus niger, which is an industrially important micro-organism used in various processes including organic acid and enzyme production, was investigated. The strategy described in this work focuses on regulation connected to p...

  20. Preparation and preclinical evaluation of (177)Lu-nimotuzumab targeting epidermal growth factor receptor overexpressing tumors

    Czech Academy of Sciences Publication Activity Database

    Beckford, Denis R.; Eigner, Sebastian; Eigner-Henke, Kateřina; Lebeda, Ondřej; Melichar, František; Beran, Miloš

    2012-01-01

    Roč. 39, č. 1 (2012), s. 3-13 ISSN 0969-8051 R&D Projects: GA MŠk 2B06165 Institutional research plan: CEZ:AV0Z10480505 Keywords : Radioimmunotherapy * Nimotuzumab * (177)Lu * Monoclonal antibody Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 2.517, year: 2012

  1. Human Factors in High-Tech Writing: Targeting the Right Tool for Professional Development.

    Science.gov (United States)

    Rehling, Louise

    1996-01-01

    Presents a method, based on a human factors approach, for helping individuals choose training in a new text technology that suits them. Offers a self-assessment questionnaire ranking preferences among firms, industries, techniques, roles, purposes for writing; then matches those preferences to typical expectations for each of several new text…

  2. Exploratory factor analysis of a Force Concept Inventory data set

    Directory of Open Access Journals (Sweden)

    Terry F. Scott

    2012-07-01

    Full Text Available We perform a factor analysis on a “Force Concept Inventory” (FCI data set collected from 2109 respondents. We address two questions: the appearance of conceptual coherence in student responses to the FCI and some consequences of this factor analysis on the teaching of Newtonian mechanics. We will highlight the apparent conflation of Newton’s third law with Newton’s first law in one of the FCI questions and suggest an approach to teaching that may avoid this issue. We also note the absence of a distinct factor interpretable as relating specifically to kinematics. Furthermore, we identify and discuss some of the technical difficulties which may be encountered when performing factor analysis on categorical data sets, such as is the case with FCI data sets.

  3. Factor analysis improves the selection of prescribing indicators

    DEFF Research Database (Denmark)

    Rasmussen, Hanne Marie Skyggedal; Søndergaard, Jens; Sokolowski, Ineta

    2006-01-01

    OBJECTIVE: To test a method for improving the selection of indicators of general practitioners' prescribing. METHODS: We conducted a prescription database study including all 180 general practices in the County of Funen, Denmark, approximately 472,000 inhabitants. Principal factor analysis was used...... to model correlation between 19 register-based indicators for the quality of non-steroidal anti-inflammatory drug (NSAID) prescribing. RESULTS: The correlation between indicators ranged widely from 0 to 0.93. Factor analysis revealed three dimensions of quality: (1) "Coxib preference", comprising...... appropriate and inappropriate prescribing, as revealed by the correlation of the indicators in the first factor. CONCLUSION: Correlation and factor analysis is a feasible method that assists the selection of indicators and gives better insight into prescribing patterns....

  4. Targeted inactivation of Snail family EMT regulatory factors by a Co(III-Ebox conjugate.

    Directory of Open Access Journals (Sweden)

    Allison S Harney

    Full Text Available Snail family proteins are core EMT (epithelial-mesenchymal transition regulatory factors that play essential roles in both development and disease processes and have been associated with metastasis in carcinomas. Snail factors are required for the formation of neural crest stem cells in most vertebrate embryos, as well as for the migratory invasive behavior of these cells. Snail factors have recently been linked to the formation of cancer stem cells, and expression of Snail proteins may be associated with tumor recurrence and resistance to chemotherapy and radiotherapy. We report that Co(III-Ebox is a potent inhibitor of Snail-mediated transcriptional repression in breast cancer cells and in the neural crest of Xenopus. We further show that the activity of Co(III-Ebox can be modulated by temperature, increasing the utility of this conjugate as a Snail inhibitor in model organisms. We exploit this feature to further delineate the requirements for Snail function during neural crest development, showing that in addition to the roles that Snail factors play in neural crest precursor formation and neural crest EMT/migration, inhibition of Snail function after the onset of neural crest migration leads to a loss of neural crest derived melanocytes. Co(III-Ebox-mediated inhibition therefore provides a powerful tool for analysing the function of these core EMT factors with unparalleled temporal resolution. Moreover, the potency of Co(III-Ebox as a Snail inhibitor in breast cancer cells suggests its potential as a therapeutic inhibitor of tumor progression and metastasis.

  5. Analysis of Factors Affecting Productivity of Horizontal Wells Based on Grey Relational Theory

    Science.gov (United States)

    Dai, Shuhui; Zhang, Jianguo; Gao, Xin; Wang, Xiande

    2018-01-01

    Taking Bp block of the Middle East as the target, on the basis of Joshi’s formula of horizontal well productivity prediction and the application of grey relevancy analysis on the average permeability, effective thickness, production pressure difference, oil saturation of reservoir and other major factors for the impact of the initial productivity of the horizontal wells, by means of obtaining the grey relational grade of influencing factors and the production of single well and optimal to optimize the combination of differential pressure, horizontal section length and other parameters, the effective exploitation of the oil field is achieved.

  6. Elemental chemical analysis of submerged targets by double-pulse laser-induced breakdown spectroscopy.

    Science.gov (United States)

    De Giacomo, A; Dell'Aglio, M; Casavola, A; Colonna, G; De Pascale, O; Capitelli, M

    2006-05-01

    Double-pulse laser-induced plasma spectroscopy (DP-LIPS) is applied to submerged targets to investigate its feasibility for elemental analysis. The role of experimental parameters, such as inter-pulse delay and detection time, has been discussed in terms of the dynamics of the laser-induced bubble produced by the first pulse and its confinement effect on the plasma produced by the second laser pulse. The analytical performance of this technique applied to targets in a water environment are discussed. The elemental analysis of submerged copper alloys by DP-LIPS has been compared with conventional (single-pulse) LIBS in air. Theoretical investigation of the plasma dynamics in water bubbles and open air has been performed.

  7. Allocating the Fixed Resources and Setting Targets in Integer Data Envelopment Analysis

    Directory of Open Access Journals (Sweden)

    Kobra Gholami

    2013-11-01

    Full Text Available Data envelopment analysis (DEA is a non-parametric approach to evaluate a set of decision making units (DMUs consuming multiple inputs to produce multiple outputs. Formally, DEA use to estimate the efficiency score into the empirical efficient frontier. Also, DEA can be used to allocate resources and set targets for future forecast. The data are continuous in the standard DEA model whereas there are many problems in the real life that data must be integer such as number of employee, machinery, expert and so on. Thus in this paper we propose an approach to allocate fixed resources and set fixed targets with selective integer assumption that is based on an integer data envelopment analysis (IDEA approach for the first time. The major aim in this approach is preserving the efficiency score of DMUs. We use the concept of benchmarking to reach this aim. The numerical example gets to illustrate the applicability of the proposed method.

  8. A novel fibroblast growth factor gene expressed in the developing nervous system is a downstream target of the chimeric homeodomain oncoprotein E2A-Pbx1.

    Science.gov (United States)

    McWhirter, J R; Goulding, M; Weiner, J A; Chun, J; Murre, C

    1997-09-01

    Pbx1 is a homeodomain transcription factor that has the ability to form heterodimers with homeodomain proteins encoded by the homeotic selector (Hox) gene complexes and increase their DNA-binding affinity and specificity. A current hypothesis proposes that interactions with Pbx1 are necessary for Hox proteins to regulate downstream target genes that in turn control growth, differentiation and morphogenesis during development. In pre B cell leukemias containing the t(1;19) chromosome translocation, Pbx1 is converted into a strong transactivator by fusion to the activation domain of the bHLH transcription factor E2A. The E2A-Pbx1 fusion protein should therefore activate transcription of genes normally regulated by Pbx1. We have used the subtractive process of representational difference analysis to identify targets of E2A-Pbx1. We show that E2A-Pbx1 can directly activate transcription of a novel member of the fibroblast growth factor family of intercellular signalling molecules, FGF-15. The FGF-15 gene is expressed in a regionally restricted pattern in the developing nervous system, suggesting that FGF-15 may play an important role in regulating cell division and patterning within specific regions of the embryonic brain, spinal cord and sensory organs.

  9. Analysis of a factor that influences cancer outpatient fatigue

    International Nuclear Information System (INIS)

    Kogure, Mayumi; Hosokawa, Mai; Takagai, Junko; Ishida, Kazuko; Kano, Taro; Kanda, Kiyoko

    2008-01-01

    The fatigue seen in many cancer cases is considered to be decrease quality of life. We clarified factors related to such fatigue and used out result to relieve fatigue. We conducted a questionnaire using the Cancer Fatigue Scale (CFS) on 204 cancer outpatients at the A hospital. We studied 16 factors influencing fatigue and analyzed the relationships among these factors and CFS scores. The mean of total fatigue scores was 23.0 points (standard deviation: 10.0). The fatigue is strong by higher than 19 points of the CFS scores. That frequency was 64.7%. The logistic regression analysis was conducted the influence factors of fatigue. Logistic regression analysis was conducted for items showing a significant difference Performance States (PS), loneliness, hormonal therapy, and radiation therapy. The conclusion of this study was to reduce fatigue in outpatient cancer treatment, it was suggested to that importance to assess a related factor of fatigue. (author)

  10. Environmental Performance in Countries Worldwide: Determinant Factors and Multivariate Analysis

    Directory of Open Access Journals (Sweden)

    Isabel Gallego-Alvarez

    2014-11-01

    Full Text Available The aim of this study is to analyze the environmental performance of countries and the variables that can influence it. At the same time, we performed a multivariate analysis using the HJ-biplot, an exploratory method that looks for hidden patterns in the data, obtained from the usual singular value decomposition (SVD of the data matrix, to contextualize the countries grouped by geographical areas and the variables relating to environmental indicators included in the environmental performance index. The sample used comprises 149 countries of different geographic areas. The findings obtained from the empirical analysis emphasize that socioeconomic factors, such as economic wealth and education, as well as institutional factors represented by the style of public administration, in particular control of corruption, are determinant factors of environmental performance in the countries analyzed. In contrast, no effect on environmental performance was found for factors relating to the internal characteristics of a country or political factors.

  11. Testing Process Factor Analysis Models Using the Parametric Bootstrap.

    Science.gov (United States)

    Zhang, Guangjian

    2018-01-01

    Process factor analysis (PFA) is a latent variable model for intensive longitudinal data. It combines P-technique factor analysis and time series analysis. The goodness-of-fit test in PFA is currently unavailable. In the paper, we propose a parametric bootstrap method for assessing model fit in PFA. We illustrate the test with an empirical data set in which 22 participants rated their effects everyday over a period of 90 days. We also explore Type I error and power of the parametric bootstrap test with simulated data.

  12. Brain derived neurotrophic factor mediated learning, fear acquisition and extinction as targets for developing novel treatments for anxiety

    Directory of Open Access Journals (Sweden)

    Karina Soares de Oliveira

    Full Text Available ABSTRACT Anxiety and obsessive-compulsive related disorders are highly prevalent and disabling disorders for which there are still treatment gaps to be explored. Fear is a core symptom of these disorders and its learning is highly dependent on the activity of the neurotrophin brain-derived neurotrophic factor (BDNF. Should BDNF-mediated fear learning be considered a target for the development of novel treatments for anxiety and obsessive-compulsive related disorders? We review the evidence that suggests that BDNF expression is necessary for the acquisition of conditioned fear, as well as for the recall of its extinction. We describe the findings related to fear learning and genetic/epigenetic manipulation of Bdnf expression in animals and BDNF allelic variants in humans. Later, we discuss how manipulation of BDNF levels represents a promising potential treatment target that may increase the benefits of therapies that extinguish previously conditioned fear.

  13. Chemotherapy, targeted agents, antiemetics and growth-factors in human milk: how should we counsel cancer patients about breastfeeding?

    Science.gov (United States)

    Pistilli, Barbara; Bellettini, Giulia; Giovannetti, Elisa; Codacci-Pisanelli, Giovanni; Azim, Hatem A; Benedetti, Giovanni; Sarno, Maria Anna; Peccatori, Fedro A

    2013-05-01

    An increasing number of women are diagnosed with cancer during pregnancy and lactation. Women are usually advised to interrupt breastfeeding during systemic anticancer treatment for fear of serious adverse effects to the nursed infant. However, the issue is poorly addressed in the literature and very few studies have evaluated the safety of breastfeeding during or after cytotoxic drugs or target agents administration. In this review we will analyze the available evidence that addresses the issue of anticancer drugs, targeted agents, antiemetics and growth-factors excretion in human milk. This could serve as a unique resource that may aid physicians in the management of breastfeeding cancer patients interested in maintaining lactation during treatment. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. Simulating Serial-Target Antibacterial Drug Synergies Using Flux Balance Analysis

    DEFF Research Database (Denmark)

    Krueger, Andrew S.; Munck, Christian; Dantas, Gautam

    2016-01-01

    Flux balance analysis (FBA) is an increasingly useful approach for modeling the behavior of metabolic systems. However, standard FBA modeling of genetic knockouts cannot predict drug combination synergies observed between serial metabolic targets, even though such synergies give rise to some...... the possibility for more accurate genome-scale predictions of drug synergies, which can be used to suggest treatments for infections and other diseases....

  15. Methodological Approach to Company Cash Flows Target-Oriented Forecasting Based on Financial Position Analysis

    OpenAIRE

    Sergey Krylov

    2012-01-01

    The article treats a new methodological approach to the company cash flows target-oriented forecasting based on its financial position analysis. The approach is featured to be universal and presumes application of the following techniques developed by the author: financial ratio values correction techniques and correcting cash flows techniques. The financial ratio values correction technique assumes to analyze and forecast company financial position while the correcting cash flows technique i...

  16. Targeting khat or targeting Somalis? A discourse analysis of project evaluations on khat abuse among Somali immigrants in Scandinavia

    Directory of Open Access Journals (Sweden)

    Nordgren Johan

    2015-09-01

    Full Text Available BACKGROUND – In Denmark, Norway and Sweden, the use of the psychoactive plant khat is widely seen as a social and health problem exclusively affecting the Somali immigrant population. Several projects by governmental and municipal bodies and agencies have been initiated to reduce khat use and abuse within this target population.

  17. Silver nanoparticles inhibit the function of hypoxia-inducible factor-1 and target genes: insight into the cytotoxicity and antiangiogenesis.

    Science.gov (United States)

    Yang, Tieshan; Yao, Qian; Cao, Fei; Liu, Qianqian; Liu, Binlei; Wang, Xiu-Hong

    Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that is activated upon exposure to hypoxic stress. It modulates a number of cellular responses including proliferation, apoptosis, angiogenesis, and metabolism by activating a panel of target genes in response to hypoxia. The HIF-1 level is often upregulated in the hypoxic microenvironment of solid tumors, which contributes to cancer treatment failure. Here we report that silver nanoparticles (AgNPs), which are widely used as an antimicrobial agent, are an effective inhibitor of HIF-1. AgNPs inhibited the activation of a HIF-dependent reporter construct after the cells were exposed to hypoxic conditions or treated with cobalt chloride, a hypoxia mimetic agent. The AgNPs also interfered with the accumulation of HIF-1α protein and the induction of the endogenous HIF target genes, VEGF-A and GLUT1. Since both HIF-1 and vascular endothelial growth factor-A play an important role in angiogenesis, AgNPs also inhibited angiogenesis in vitro. Our data reveal a new mechanism of how AgNPs act on cellular function, that is, they disrupt HIF signaling pathway. This finding provides a novel insight into how AgNPs can inhibit cancer cell growth and angiogenesis.

  18. Joint Cross-Range Scaling and 3D Geometry Reconstruction of ISAR Targets Based on Factorization Method.

    Science.gov (United States)

    Lei Liu; Feng Zhou; Xue-Ru Bai; Ming-Liang Tao; Zi-Jing Zhang

    2016-04-01

    Traditionally, the factorization method is applied to reconstruct the 3D geometry of a target from its sequential inverse synthetic aperture radar images. However, this method requires performing cross-range scaling to all the sub-images and thus has a large computational burden. To tackle this problem, this paper proposes a novel method for joint cross-range scaling and 3D geometry reconstruction of steadily moving targets. In this method, we model the equivalent rotational angular velocity (RAV) by a linear polynomial with time, and set its coefficients randomly to perform sub-image cross-range scaling. Then, we generate the initial trajectory matrix of the scattering centers, and solve the 3D geometry and projection vectors by the factorization method with relaxed constraints. After that, the coefficients of the polynomial are estimated from the projection vectors to obtain the RAV. Finally, the trajectory matrix is re-scaled using the estimated rotational angle, and accurate 3D geometry is reconstructed. The two major steps, i.e., the cross-range scaling and the factorization, are performed repeatedly to achieve precise 3D geometry reconstruction. Simulation results have proved the effectiveness and robustness of the proposed method.

  19. Genome-wide targeting of the epigenetic regulatory protein CTCF to gene promoters by the transcription factor TFII-I.

    Science.gov (United States)

    Peña-Hernández, Rodrigo; Marques, Maud; Hilmi, Khalid; Zhao, Teijun; Saad, Amine; Alaoui-Jamali, Moulay A; del Rincon, Sonia V; Ashworth, Todd; Roy, Ananda L; Emerson, Beverly M; Witcher, Michael

    2015-02-17

    CCCTC-binding factor (CTCF) is a key regulator of nuclear chromatin structure and gene regulation. The impact of CTCF on transcriptional output is highly varied, ranging from repression to transcriptional pausing and transactivation. The multifunctional nature of CTCF may be directed solely through remodeling chromatin architecture. However, another hypothesis is that the multifunctional nature of CTCF is mediated, in part, through differential association with protein partners having unique functions. Consistent with this hypothesis, our mass spectrometry analyses of CTCF interacting partners reveal a previously undefined association with the transcription factor general transcription factor II-I (TFII-I). Biochemical fractionation of CTCF indicates that a distinct CTCF complex incorporating TFII-I is assembled on DNA. Unexpectedly, we found that the interaction between CTCF and TFII-I is essential for directing CTCF to the promoter proximal regulatory regions of target genes across the genome, particularly at genes involved in metabolism. At genes coregulated by CTCF and TFII-I, we find knockdown of TFII-I results in diminished CTCF binding, lack of cyclin-dependent kinase 8 (CDK8) recruitment, and an attenuation of RNA polymerase II phosphorylation at serine 5. Phenotypically, knockdown of TFII-I alters the cellular response to metabolic stress. Our data indicate that TFII-I directs CTCF binding to target genes, and in turn the two proteins cooperate to recruit CDK8 and enhance transcription initiation.

  20. Involvement of pro-inflammatory cytokines and growth factors in the pathogenesis of Dupuytren's contracture: a novel target for a possible future therapeutic strategy?

    Science.gov (United States)

    Bianchi, Enrica; Taurone, Samanta; Bardella, Lia; Signore, Alberto; Pompili, Elena; Sessa, Vincenzo; Chiappetta, Caterina; Fumagalli, Lorenzo; Di Gioia, Cira; Pastore, Francesco S; Scarpa, Susanna; Artico, Marco

    2015-10-01

    Dupuytren's contracture (DC) is a benign fibro-proliferative disease of the hand causing fibrotic nodules and fascial cords which determine debilitating contracture and deformities of fingers and hands. The present study was designed to characterize pro-inflammatory cytokines and growth factors involved in the pathogenesis, progression and recurrence of this disease, in order to find novel targets for alternative therapies and strategies in controlling DC. The expression of pro-inflammatory cytokines and of growth factors was detected by immunohistochemistry in fibrotic nodules and normal palmar fascia resected respectively from patients affected by DC and carpal tunnel syndrome (CTS; as negative controls). Reverse transcription (RT)-PCR analysis and immunofluorescence were performed to quantify the expression of transforming growth factor (TGF)-β1, interleukin (IL)-1β and vascular endothelial growth factor (VEGF) by primary cultures of myofibroblasts and fibroblasts isolated from Dupuytren's nodules. Histological analysis showed high cellularity and high proliferation rate in Dupuytren's tissue, together with the presence of myofibroblastic isotypes; immunohistochemical staining for macrophages was completely negative. In addition, a strong expression of TGF-β1, IL-1β and VEGF was evident in the extracellular matrix and in the cytoplasm of fibroblasts and myofibroblasts in Dupuytren's nodular tissues, as compared with control tissues. These results were confirmed by RT-PCR and by immunofluorescence in pathological and normal primary cell cultures. These preliminary observations suggest that TGF-β1, IL-1β and VEGF may be considered potential therapeutic targets in the treatment of Dupuytren's disease (DD). © 2015 Authors; published by Portland Press Limited.

  1. The Epstein-Barr virus microRNA BART11-5p targets the early B-cell transcription factor EBF1.

    Science.gov (United States)

    Ross, Nathan; Gandhi, Maher K; Nourse, Jamie P

    2013-01-01

    Epstein-Barr virus (EBV) is a ubiquitous B-cell trophic herpesvirus associated with a variety of histologically diverse B-cell lymphomas, each associated with specific viral-latency gene expression programs. Initial infection drives resting B-cells to differentiate via an atypical germinal centre reaction into memory B-cells, where the virus resides in a latent state. The mechanisms that underpin this process have yet to be fully elucidated. EBV expresses more than 40 microRNAs (miRNAs). The alternatively spliced BamHI A rightward transcripts (BARTs) are the template for two large miRNA clusters (BARTs A and B), that comprise the majority of all known EBV-miRNAs. Although BART-miRNAs are abundantly expressed in all latency programs, few BART-miRNA targets have been identified and their function is poorly understood. The early B-cell factor 1 (EBF1) was identified using bioinformaticss analysis as a novel target of EBV-miRNA BART11-5p, encoded by BART cluster B. EBF1 is an important B-cell transcription factor that regulates many B-cell specific genes including Pax5, BCR and CD40 and is critical for germinal centre formation. Using luciferase reporter assays and a series of BART-constructs, we confirmed silencing via the EBF1 3' untranslated region (UTR) and identified the target site as 2137-2159 bp after the stop codon. Results were confirmed following transfection of a BART11-5p mimic, which was able to silence via the predicted target site. Our findings highlight a potential role of BART-miRNAs in the regulation of B-cell differentiation.

  2. Therapeutic targeting of Krüppel-like factor 4 abrogates microglial activation

    Directory of Open Access Journals (Sweden)

    Kaushik Deepak

    2012-03-01

    Full Text Available Abstract Background Neuroinflammation occurs as a result of microglial activation in response to invading micro-organisms or other inflammatory stimuli within the central nervous system. According to our earlier findings, Krüppel-like factor 4 (Klf4, a zinc finger transcription factor, is involved in microglial activation and subsequent release of proinflammatory cytokines, tumor necrosis factor alpha, macrophage chemoattractant protein-1 and interleukin-6 as well as proinflammatory enzymes, inducible nitric oxide synthase and cyclooxygenase-2 in lipopolysaccharide-treated microglial cells. Our current study focuses on finding the molecular mechanism of the anti-inflammatory activities of honokiol in lipopolysaccharide-treated microglia with emphasis on the regulation of Klf4. Methods For in vitro studies, mouse microglial BV-2 cell lines as well as primary microglia were treated with 500 ng/mL lipopolysaccharide as well as 1 μM and 10 μM of honokiol. We cloned full-length Klf4 cDNA in pcDNA3.1 expression vector and transfected BV-2 cells with this construct using lipofectamine for overexpression studies. For in vivo studies, brain tissues were isolated from BALB/c mice treated with 5 mg/kg body weight of lipopolysaccharide either with or without 2.5 or 5 mg/kg body weight of honokiol. Expression of Klf4, cyclooxygenase-2, inducible nitric oxide synthase and phospho-nuclear factor-kappa B was measured using immunoblotting. We also measured the levels of cytokines, reactive oxygen species and nitric oxide in different conditions. Results Our findings suggest that honokiol can substantially downregulate the production of proinflammatory cytokines and inflammatory enzymes in lipopolysaccharide-stimulated microglia. In addition, honokiol downregulates lipopolysaccharide-induced upregulation of both Klf4 and phospho-nuclear factor-kappa B in these cells. We also found that overexpression of Klf4 in BV-2 cells suppresses the anti

  3. Globally Optimized Targeted Mass Spectrometry: Reliable Metabolomics Analysis with Broad Coverage.

    Science.gov (United States)

    Gu, Haiwei; Zhang, Ping; Zhu, Jiangjiang; Raftery, Daniel

    2015-12-15

    Targeted detection is one of the most important methods in mass spectrometry (MS)-based metabolomics; however, its major limitation is the reduced metabolome coverage that results from the limited set of targeted metabolites typically used in the analysis. In this study we describe a new approach, globally optimized targeted (GOT)-MS, that combines many of the advantages of targeted detection and global profiling in metabolomics analysis, including the capability to detect unknowns, broad metabolite coverage, and excellent quantitation. The key step in GOT-MS is a global search of precursor and product ions using a single liquid chromatography-triple quadrupole (LC-QQQ) mass spectrometer. Here, focused on measuring serum metabolites, we obtained 595 precursor ions and 1 890 multiple reaction monitoring (MRM) transitions, under positive and negative ionization modes in the mass range of 60-600 Da. For many of the MRMs/metabolites under investigation, the analytical performance of GOT-MS is better than or at least comparable to that obtained by global profiling using a quadrupole-time-of-flight (Q-TOF) instrument of similar vintage. Using a study of serum metabolites in colorectal cancer (CRC) as a representative example, GOT-MS significantly outperformed a large targeted MS assay containing ∼160 biologically important metabolites and provided a complementary approach to traditional global profiling using Q-TOF-MS. GOT-MS thus expands and optimizes the detection capabilities for QQQ-MS through a novel approach and should have the potential to significantly advance both basic and clinical metabolic research.

  4. Factors affecting ambulance utilization for asthma attack treatment: understanding where to target interventions.

    Science.gov (United States)

    Raun, L H; Ensor, K B; Campos, L A; Persse, D

    2015-05-01

    Asthma is a serious, sometimes fatal condition, in which attacks vary in severity, potentially requiring emergency medical services (EMS) ambulance treatment. A portion of asthma attacks requiring EMS ambulance treatment may be prevented with improved education and access to care. The aim of this study was to identify areas of the city with high rates of utilization of EMS ambulance for treatment, and the demographics, socio-economic status, and time of day associated with these rates, to better target future interventions to prevent emergencies and reduce cost. A cross-sectional study was conducted on individuals in Houston, TX (USA) requiring ambulance treatment for asthma attacks from 2004 to 2011. 12,155 EMS ambulance-treated asthma attack cases were linked to census tracts. High rate treatment areas were identified with geospatial mapping. Census tract demographic characteristics of these high rate areas were compared with the remainder of the city using logistic regression. The association between case level demographics and the time of day of asthma attack within the high rate area was also assessed with logistic regression. EMS ambulance-treated high rate areas were identified and found to have a utilization incidence rate over six times higher per 100,000 people than the remainder of the city. There is an increased risk of location in this high rate area with a census tract level increase of percent of population: earning less than $10,000 yearly income (RR 1.21, 1.16-1.26), which is black (RR 1.08, 1.07-1.10), which is female (RR 1.34, 1.20-1.49) and have obtained less than a high school degree (RR 1.02, 1.01-1.03). Within the high rate area, case level data indicates an increased risk of requiring an ambulance after normal doctor office hours for men compared with women (RR 1.13, 1.03-1.22), for black compared with Hispanic ethnicity (RR 1.31, 1.08-1.59), or for adults (less than 41 and greater than 60) compared with children. Interventions to prevent

  5. Silver nanoparticles inhibit the function of hypoxia-inducible factor-1 and target genes: insight into the cytotoxicity and antiangiogenesis

    Directory of Open Access Journals (Sweden)

    Yang T

    2016-12-01

    Full Text Available Tieshan Yang,1 Qian Yao,1 Fei Cao,1 Qianqian Liu,1 Binlei Liu,2 Xiu-Hong Wang1 1Laboratory for Biomedical Photonics, Institute of Laser Engineering, Beijing University of Technology, 2Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China Abstract: Hypoxia-inducible factor-1 (HIF-1 is a transcription factor that is activated upon exposure to hypoxic stress. It modulates a number of cellular responses including proliferation, apoptosis, angiogenesis, and metabolism by activating a panel of target genes in response to hypoxia. The HIF-1 level is often upregulated in the hypoxic microenvironment of solid tumors, which contributes to cancer treatment failure. Here we report that silver nanoparticles (AgNPs, which are widely used as an antimicrobial agent, are an effective inhibitor of HIF-1. AgNPs inhibited the activation of a HIF-dependent reporter construct after the cells were exposed to hypoxic conditions or treated with cobalt chloride, a hypoxia mimetic agent. The AgNPs also interfered with the accumulation of HIF-1α protein and the induction of the endogenous HIF target genes, VEGF-A and GLUT1. Since both HIF-1 and vascular endothelial growth factor-A play an important role in angiogenesis, AgNPs also inhibited angiogenesis in vitro. Our data reveal a new mechanism of how AgNPs act on cellular function, that is, they disrupt HIF signaling pathway. This finding provides a novel insight into how AgNPs can inhibit cancer cell growth and angiogenesis. Keywords: silver nanoparticles (AgNPs, hypoxia-inducible factor, transcriptional activity, vascular endothelial growth factor-A, angiogenesis

  6. Chenodeoxycholic Acid Reduces Hypoxia Inducible Factor-1α Protein and Its Target Genes.

    Directory of Open Access Journals (Sweden)

    Yunwon Moon

    Full Text Available This study evaluated HIF-1α inhibitors under different hypoxic conditions, physiological hypoxia (5% O2 and severe hypoxia (0.1% O2. We found that chenodeoxy cholic acid (CDCA reduced the amount of HIF-1α protein only under physiological hypoxia but not under severe hypoxia without decreasing its mRNA level. By using a proteasome inhibitor MG132 and a translation inhibitor cyclohexamide, we showed that CDCA reduced HIF-1α protein by decreasing its translation but not by enhancing its degradation. The following findings indicated that farnesoid X receptor (FXR, a CDCA receptor and its target gene, Small heterodimer partner (SHP are not involved in this effect of CDCA. Distinctly from CDCA, MG132 prevented SHP and an exogenous FXR agonist, GW4064 from reducing HIF-1α protein. Furthermore a FXR antagonist, guggulsterone failed to prevent CDCA from decreasing HIF-1α protein. Furthermore, guggulsterone by itself reduced HIF-1α protein even in the presence of MG132. These findings suggested that CDCA and guggulsterone reduced the translation of HIF-1α in a mechanism which FXR and SHP are not involved. This study reveals novel therapeutic functions of traditional nontoxic drugs, CDCA and guggulsterone, as inhibitors of HIF-1α protein.

  7. Modulation of the Endocannabinoid System: Vulnerability Factor and New Treatment Target for Stimulant Addiction.

    Directory of Open Access Journals (Sweden)

    Stéphanie eOlière

    2013-09-01

    Full Text Available Cannabis is one of the most widely used illicit substance among users of stimulants such as cocaine and amphetamine. Interestingly, recent accumulating evidence points toward the involvement of the endocannabinoid system (ECBS in the neurobiological processes related to stimulant addiction. This article presents an up-to-date review with deep-insights into the pivotal role of the ECBS in the neurobiology of stimulant addiction and the effects of its modulation on addictive behaviors. The aims of this article are to: 1 review the role of cannabis use and ECBS modulation in the neurobiological substrates of psychostimulant addiction and 2 evaluate the potential of cannabinoid-based pharmacological strategies to treat stimulant addiction. A growing number of studies support a critical role of the ECBS and its modulation by synthetic or natural cannabinoid in various neurobiological and behavioral aspects of stimulants addiction. Thus, cannabinoids modulate brain reward systems closely involved in stimulants addiction, and provide further evidence that the cannabinoid system could be explored as a potential drug discovery target for treating addiction across different classes of stimulants.

  8. MEANING OF TARGET AMBIGUITY FACTOR IN INTELLECTUAL TECHNOLOGIES OF SCIENTIFIC SEARCH

    Directory of Open Access Journals (Sweden)

    V. M. Коleshko

    2008-01-01

    Full Text Available The main peculiar feature of an intellectual system orientated to formulation of original scientific hypothesis, non-trivial technical solutions is an initial target ambiguity of creative search. Process concerning creation of new knowledge in such system presuppose chaotic steps directed on hypothesis synthesis and their improvement, cancellation of non-productive searching methods and advancement of new scientific theories. Formation of new knowledge which generally has random character at the initial stage gradually becomes more ordered, motivated to obtain a concrete result due to development of searching process. Both components of the intellectual medium (a human being and a machine have so to speak an equilibrium in their actions, actively interacting and supplementing each other in the most creative procedures of hypothesis synthesis. Role difference resides in that a computer provides its formal logical and information resource for solution selection, and a researcher is assigned to carry out an additional task that is to take decisions about correctness of scientific hypothesis

  9. The control of male fertility by spermatid-specific factors: searching for contraceptive targets from spermatozoon's head to tail

    Science.gov (United States)

    Chen, Su-Ren; Batool, Aalia; Wang, Yu-Qian; Hao, Xiao-Xia; Chang, Chawn-Shang; Cheng, C Yan; Liu, Yi-Xun

    2016-01-01

    Male infertility due to abnormal spermatozoa has been reported in both animals and humans, but its pathogenic causes, including genetic abnormalities, remain largely unknown. On the other hand, contraceptive options for men are limited, and a specific, reversible and safe method of male contraception has been a long-standing quest in medicine. Some progress has recently been made in exploring the effects of spermatid-specifical genetic factors in controlling male fertility. A comprehensive search of PubMed for articles and reviews published in English before July 2016 was carried out using the search terms ‘spermiogenesis failure', ‘globozoospermia', ‘spermatid-specific', ‘acrosome', ‘infertile', ‘manchette', ‘sperm connecting piece', ‘sperm annulus', ‘sperm ADAMs', ‘flagellar abnormalities', ‘sperm motility loss', ‘sperm ion exchanger' and ‘contraceptive targets'. Importantly, we have opted to focus on articles regarding spermatid-specific factors. Genetic studies to define the structure and physiology of sperm have shown that spermatozoa appear to be one of the most promising contraceptive targets. Here we summarize how these spermatid-specific factors regulate spermiogenesis and categorize them according to their localization and function from spermatid head to tail (e.g., acrosome, manchette, head-tail conjunction, annulus, principal piece of tail). In addition, we emphatically introduce small-molecule contraceptives, such as BRDT and PPP3CC/PPP3R2, which are currently being developed to target spermatogenic-specific proteins. We suggest that blocking the differentiation of haploid germ cells, which rarely affects early spermatogenic cell types and the testicular microenvironment, is a better choice than spermatogenic-specific proteins. The studies described here provide valuable information regarding the genetic and molecular defects causing male mouse infertility to improve our understanding of the importance of spermatid

  10. An analysis of possible off target effects following CAS9/CRISPR targeted deletions of neuropeptide gene enhancers from the mouse genome.

    Science.gov (United States)

    Hay, Elizabeth Anne; Khalaf, Abdulla Razak; Marini, Pietro; Brown, Andrew; Heath, Karyn; Sheppard, Darrin; MacKenzie, Alasdair

    2017-08-01

    We have successfully used comparative genomics to identify putative regulatory elements within the human genome that contribute to the tissue specific expression of neuropeptides such as galanin and receptors such as CB1. However, a previous inability to rapidly delete these elements from the mouse genome has prevented optimal assessment of their function in-vivo. This has been solved using CAS9/CRISPR genome editing technology which uses a bacterial endonuclease called CAS9 that, in combination with specifically designed guide RNA (gRNA) molecules, cuts specific regions of the mouse genome. However, reports of "off target" effects, whereby the CAS9 endonuclease is able to cut sites other than those targeted, limits the appeal of this technology. We used cytoplasmic microinjection of gRNA and CAS9 mRNA into 1-cell mouse embryos to rapidly generate enhancer knockout mouse lines. The current study describes our analysis of the genomes of these enhancer knockout lines to detect possible off-target effects. Bioinformatic analysis was used to identify the most likely putative off-target sites and to design PCR primers that would amplify these sequences from genomic DNA of founder enhancer deletion mouse lines. Amplified DNA was then sequenced and blasted against the mouse genome sequence to detect off-target effects. Using this approach we were unable to detect any evidence of off-target effects in the genomes of three founder lines using any of the four gRNAs used in the analysis. This study suggests that the problem of off-target effects in transgenic mice have been exaggerated and that CAS9/CRISPR represents a highly effective and accurate method of deleting putative neuropeptide gene enhancer sequences from the mouse genome. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Level of response to alcohol as a factor for targeted prevention in college students.

    Science.gov (United States)

    Savage, Jeanne E; Neale, Zoe; Cho, Seung Bin; Hancock, Linda; Kalmijn, Jelger A; Smith, Tom L; Schuckit, Marc A; Donovan, Kristen Kidd; Dick, Danielle M

    2015-11-01

    Heavy alcohol consumption and alcohol problems among college students are widespread and associated with negative outcomes for individuals and communities. Although current methods for prevention and intervention programming have some demonstrated efficacy, heavy drinking remains a problem. A previous pilot study and a recent large-scale evaluation (Schuckit et al., , ) found that a tailored prevention program based on a risk factor for heavy drinking, low level of response (low LR) to alcohol, was more effective at reducing heavy drinking than a state-of-the-art (SOTA) standard prevention program for individuals with the low LR risk factor. This study enrolled 231 first-semester college freshmen with either high or low LR into the same level of response-based (LRB) or SOTA online prevention programs as in the previous reports (consisting of 4 weeks of video modules), as well as a group of matched controls not receiving alcohol prevention, and compared changes in alcohol use between these groups across a 6-month period. Individuals in alcohol prevention programs had a greater reduction in maximum drinks per occasion and alcohol use disorder symptoms than controls. There was limited evidence for interactions between LR and prevention group in predicting change in alcohol use behaviors; only among participants with strict adherence to the program was there an interaction between LR and program in predicting maximum drinks per occasion. However, overall, low LR individuals showed greater decreases in drinking behaviors, especially risky behaviors (e.g., maximum drinks, frequency of heavy drinking) than high LR individuals. These results indicate that prevention programs, including brief and relatively inexpensive web-based programs, may be effective for persons at highest risk for heavier drinking, such as those with a low LR. Tailored programs may provide incremental benefits under some conditions. Long-term follow-ups and further investigations of tailored

  12. Endoplasmic Reticulum-Associated Degradation Factor ERLIN2: Oncogenic Roles and Molecular Targeting of Breast Cancer

    Science.gov (United States)

    2013-06-01

    Han , W. F., Chen, T., Bornman, D. M., Gabrielson, E. W. and Pizer, E. S. (2003) Regulation of fatty acid synthase expression in breast cancer by sterol...chemically defined medium. Cancer Res. 42, 3858–3863 5 Yang, Y. A., Morin, P. J., Han , W. F., Chen, T., Bornman, D. M., Gabrielson, E. W. and Pizer, E. S...factor. Cell 2001; 107: 881-891. [26] X Shen, RE Ellis, K Lee, CY Liu, K Yang, A Solo - mon, H Yoshida, R Morimoto, DM Kurnit, K Mori and RJ Kaufman

  13. Critical analysis of the potential for therapeutic targeting of mammalian target of rapamycin (mTOR in gastric cancer

    Directory of Open Access Journals (Sweden)

    Inokuchi M

    2014-04-01

    Full Text Available Mikito Inokuchi,1 Keiji Kato,1 Kazuyuki Kojima,2 Kenichi Sugihara1 1Department of Surgical Oncology, 2Department of Minimally Invasive Surgery, Tokyo Medical and Dental University, Tokyo, Japan Abstract: Multidisciplinary treatment including chemotherapy has become the global standard of care for patients with metastatic gastric cancer (mGC; nonetheless, survival remains poor. Although many molecular-targeted therapies have been developed for various cancers, only anti-HER2 treatment has produced promising results in patients with mGC. Mammalian target of rapamycin (mTOR plays a key role in cell proliferation, antiapoptosis, and metastasis in signaling pathways from the tyrosine kinase receptor, and its activation has been demonstrated in gastric cancer (GC cells. This review discusses the clinical relevance of mTOR in GC and examines its potential as a therapeutic target in patients with mGC. Preclinical studies in animal models suggest that suppression of the mTOR pathway inhibits the proliferation of GC cells and delays tumor progression. The mTOR inhibitor everolimus has been evaluated as second- or third-line treatment in clinical trials. Adverse events were well tolerated although the effectiveness of everolimus alone was limited. Everolimus is now being evaluated in combination with chemotherapy in Phase III clinical studies in this subgroup of patients. Two Phase III studies include exploratory biomarker research designed to evaluate the predictive value of the expression or mutation of molecules related to the Akt/mTOR signaling pathway. These biomarker studies may lead to the realization of targeted therapy for selected patients with mGC in the future. Keywords: gastric cancer, mTOR, everolimus

  14. Critical analysis of the potential for targeting STAT3 in human malignancy

    Directory of Open Access Journals (Sweden)

    Peyser ND

    2013-07-01

    Full Text Available Noah D Peyser, Jennifer R Grandis Departments of Otolaryngology and Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Abstract: The signal transducer and activator of transcription (STAT family of proteins was originally discovered in the context of normal cell biology where they function to transduce intracellular and extracellular signals to the nucleus, ultimately leading to transcription of specific target genes and downstream phenotypic effects. It was quickly appreciated that the STATs, especially STAT3, play a fundamental role in human malignancy. In contrast to normal biology in which transient STAT3 signaling is strictly regulated by a tightly coordinated network of activators and deactivators, STAT3 is constitutively activated in human malignancies. Constitutive STAT3 signaling has been associated with many cancerous phenotypes across nearly all human cancers, including the upregulation of cell growth, proliferation, survival, and motility, among others. Studies involving candidate preclinical STAT3 inhibitors have further demonstrated that the reversal of these phenotypes results from pharmacologic or genetic inhibition of STAT3, suggesting that STAT3 may be a promising target for clinical interventions. Indeed, a Phase 0 clinical trial involving a STAT3 decoy oligonucleotide demonstrated that STAT3 is a druggable target in human tumors. Because of the ubiquity of overactive STAT3 in cancer, its role in promoting a wide variety of cancerous phenotypes, and the strong clinical and preclinical studies performed to date, STAT3 represents a promising target for the development of inhibitors for the treatment of human cancers. Keywords: cancer, target, STAT3, transcription factor

  15. UHR-Q-TOF Analysis Can Address Common Challenges in Targeted and Untargeted Metabolomics

    Science.gov (United States)

    Zurek, G.; Krug, D.; Muller, R.; Barsch, A.

    2011-01-01

    Here, we present an ESI-UHR-Q-TOF based analysis of myxobacterial secondary metabolites, which permits to solve several challenges frequently encountered in metabolite profiling studies. Myxobacteria are promising producers of natural products exhibiting potent biological activities, and several myxobacterial metabolites are currently under investigation as potential leads for novel drugs. However, the myxobacteria are also a striking example for the divergence between the genetic capacity for the production of secondary metabolites and the number of compounds that could be characterised to date. Wild type and mutant strains were analyzed concerning the production patterns of known metabolites and with regard to the discovery of new metabolites. Sample throughput: Since mass accuracy and resolution of TOF instruments are independent of the acquisition rate, they are perfectly suited for a coupling to UHPLC separations. These hyphenations enable a reduction of analysis time in combination with a high chromatographic resolution and therefore permit an increased sample throughput. The UHR-TOF analysis revealed that an acquisition rate of up to 20Hz did not compromise the achieved mass accuracy or resolution. Targeted and untargeted metabolite profiling: Acquisition of full scan accurate mass spectra enable the targeted screening for known compounds e.g. from the class of DKxanthenes based on very selective high resolution EIC (hrEIC) traces with small mass windows of 1.0–0.5mDa. A comparison of several datasets following a “comprehensive feature extraction” combined with a statistical analysis permits an untargeted discovery of novel biomarkers using the same data files as for the targeted analysis. Identification: Even a mass accuracy of 0.1ppm is not sufficient for an unambiguous formula identification for m/z values above 500. A combination of accurate mass data and isotopic pattern information in MS and MS/MS spectra can extend this m/z range for reliable

  16. In-silico Metabolome Target Analysis Towards PanC-based Antimycobacterial Agent Discovery.

    Science.gov (United States)

    Khoshkholgh-Sima, Baharak; Sardari, Soroush; Izadi Mobarakeh, Jalal; Khavari-Nejad, Ramezan Ali

    2015-01-01

    Mycobacterium tuberculosis, the main cause of tuberculosis (TB), has still remained a global health crisis especially in developing countries. Tuberculosis treatment is a laborious and lengthy process with high risk of noncompliance, cytotoxicity adverse events and drug resistance in patient. Recently, there has been an alarming rise of drug resistant in TB. In this regard, it is an unmet need to develop novel antitubercular medicines that target new or more effective biochemical pathways to prevent drug resistant Mycobacterium. Integrated study of metabolic pathways through in-silico approach played a key role in antimycobacterial design process in this study. Our results suggest that pantothenate synthetase (PanC), anthranilate phosphoribosyl transferase (TrpD) and 3-isopropylmalate dehydratase (LeuD) might be appropriate drug targets. In the next step, in-silico ligand analysis was used for more detailed study of chemical tractability of targets. This was helpful to identify pantothenate synthetase (PanC, Rv3602c) as the best target for antimycobacterial design procedure. Virtual library screening on the best ligand of PanC was then performed for inhibitory ligand design. At the end, five chemical intermediates showed significant inhibition of Mycobacterium bovis with good selectivity indices (SI) ≥10 according to Tuberculosis Antimicrobial Acquisition & Coordinating Facility of US criteria for antimycobacterial screening programs.

  17. Identification of Cell Surface Targets through Meta-analysis of Microarray Data

    Directory of Open Access Journals (Sweden)

    Henry Haeberle

    2012-07-01

    Full Text Available High-resolution image guidance for resection of residual tumor cells would enable more precise and complete excision for more effective treatment of cancers, such as medulloblastoma, the most common pediatric brain cancer. Numerous studies have shown that brain tumor patient outcomes correlate with the precision of resection. To enable guided resection with molecular specificity and cellular resolution, molecular probes that effectively delineate brain tumor boundaries are essential. Therefore, we developed a bioinformatics approach to analyze micro-array datasets for the identification of transcripts that encode candidate cell surface biomarkers that are highly enriched in medulloblastoma. The results identified 380 genes with greater than a two-fold increase in the expression in the medulloblastoma compared with that in the normal cerebellum. To enrich for targets with accessibility for extracellular molecular probes, we further refined this list by filtering it with gene ontology to identify genes with protein localization on, or within, the plasma membrane. To validate this meta-analysis, the top 10 candidates were evaluated with immunohistochemistry. We identified two targets, fibrillin 2 and EphA3, which specifically stain medulloblastoma. These results demonstrate a novel bioinformatics approach that successfully identified cell surface and extracellular candidate markers enriched in medulloblastoma versus adjacent cerebellum. These two proteins are high-value targets for the development of tumor-specific probes in medulloblastoma. This bioinformatics method has broad utility for the identification of accessible molecular targets in a variety of cancers and will enable probe development for guided resection.

  18. Expression analysis of miRNA and target mRNAs in esophageal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Meng, X.R. [Oncology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou (China); Lu, P. [Gastrointestinal Surgery Department, People' s Hospital of Zhengzhou, Zhengzhou (China); Mei, J.Z.; Liu, G.J. [Medical Oncology Department, People' s Hospital of Zhengzhou, Zhengzhou (China); Fan, Q.X. [Oncology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou (China)

    2014-08-01

    We aimed to investigate miRNAs and related mRNAs through a network-based approach in order to learn the crucial role that they play in the biological processes of esophageal cancer. Esophageal squamous-cell carcinoma (ESCC) and adenocarcinoma (EAC)-related miRNA and gene expression data were downloaded from the Gene Expression Omnibus database, and differentially expressed miRNAs and genes were selected. Target genes of differentially expressed miRNAs were predicted and their regulatory networks were constructed. Differentially expressed miRNA analysis selected four miRNAs associated with EAC and ESCC, among which hsa-miR-21 and hsa-miR-202 were shared by both diseases. hsa-miR-202 was reported for the first time to be associated with esophageal cancer in the present study. Differentially expressed miRNA target genes were mainly involved in cancer-related and signal-transduction pathways. Functional categories of these target genes were related to transcriptional regulation. The results may indicate potential target miRNAs and genes for future investigations of esophageal cancer.

  19. Analysis on Target Detection and Classification in LTE Based Passive Forward Scattering Radar.

    Science.gov (United States)

    Raja Abdullah, Raja Syamsul Azmir; Abdul Aziz, Noor Hafizah; Abdul Rashid, Nur Emileen; Ahmad Salah, Asem; Hashim, Fazirulhisyam

    2016-09-29

    The passive bistatic radar (PBR) system can utilize the illuminator of opportunity to enhance radar capability. By utilizing the forward scattering technique and procedure into the specific mode of PBR can provide an improvement in target detection and classification. The system is known as passive Forward Scattering Radar (FSR). The passive FSR system can exploit the peculiar advantage of the enhancement in forward scatter radar cross section (FSRCS) for target detection. Thus, the aim of this paper is to show the feasibility of passive FSR for moving target detection and classification by experimental analysis and results. The signal source is coming from the latest technology of 4G Long-Term Evolution (LTE) base station. A detailed explanation on the passive FSR receiver circuit, the detection scheme and the classification algorithm are given. In addition, the proposed passive FSR circuit employs the self-mixing technique at the receiver; hence the synchronization signal from the transmitter is not required. The experimental results confirm the passive FSR system's capability for ground target detection and classification. Furthermore, this paper illustrates the first classification result in the passive FSR system. The great potential in the passive FSR system provides a new research area in passive radar that can be used for diverse remote monitoring applications.

  20. A method of factor analysis for shape coordinates.

    Science.gov (United States)

    Bookstein, Fred L

    2017-10-01

    Currently the most common reporting style for a geometric morphometric (GMM) analysis of anthropological data begins with the principal components of the shape coordinates to which the original landmark data have been converted. But this focus often frustrates the organismal biologist, mainly because principal component analysis (PCA) is not aimed at scientific interpretability of the loading patterns actually uncovered. The difficulty of making biological sense of a PCA is heightened by aspects of the shape coordinate setting that further diverge from our intuitive expectations of how morphometric measurements ought to combine. More than 50 years ago one of our sister disciplines, psychometrics, managed to build an algorithmic route from principal component analysis to scientific understanding via the toolkit generally known as factor analysis. This article introduces a modification of one standard factor-analysis approach, Henry Kaiser's varimax rotation of 1958, that accommodates two of the major differences between the GMM context and the psychometric context for these approaches: the coexistence of "general" and "special" factors of form as adumbrated by Sewall Wright, and the typical loglinearity of partial warp variance as a function of bending energy. I briefly explain the history of principal components in biometrics and the contrast with factor analysis, introduce the modified varimax algorithm I am recommending, and work three examples that are reanalyses of previously published cranial data sets. A closing discussion emphasizes the desirability of superseding PCA by algorithms aimed at anthropological understanding rather than classification or ordination. © 2017 Wiley Periodicals, Inc.

  1. IκB kinase ε targets interferon regulatory factor 1 in activated T lymphocytes.

    Science.gov (United States)

    Sgarbanti, Marco; Marsili, Giulia; Remoli, Anna Lisa; Stellacci, Emilia; Mai, Antonello; Rotili, Dante; Perrotti, Edvige; Acchioni, Chiara; Orsatti, Roberto; Iraci, Nunzio; Ferrari, Mathieu; Borsetti, Alessandra; Hiscott, John; Battistini, Angela

    2014-03-01

    IκB kinase ε (IKK-ε) has an essential role as a regulator of innate immunity, functioning downstream of pattern recognition receptors to modulate NF-κB and interferon (IFN) signaling. In the present study, we investigated IKK-ε activation following T cell receptor (TCR)/CD28 stimulation of primary CD4(+) T cells and its role in the stimulation of a type I IFN response. IKK-ε was activated following TCR/CD28 stimulation of primary CD4(+) T cells; however, in T cells treated with poly(I·C), TCR/CD28 costimulation blocked induction of IFN-β transcription. We demonstrated that IKK-ε phosphorylated the transcription factor IFN regulatory factor 1 (IRF-1) at amino acid (aa) 215/219/221 in primary CD4(+) T cells and blocked its transcriptional activity. At the mechanistic level, IRF-1 phosphorylation impaired the physical interaction between IRF-1 and the NF-κB RelA subunit and interfered with PCAF-mediated acetylation of NF-κB RelA. These results demonstrate that TCR/CD28 stimulation of primary T cells stimulates IKK-ε activation, which in turn contributes to suppression of IFN-β production.

  2. The Nerve Growth Factor Signaling and Its Potential as Therapeutic Target for Glaucoma

    Directory of Open Access Journals (Sweden)

    Haitao Wang

    2014-01-01

    Full Text Available Neuroprotective therapies which focus on factors leading to retinal ganglion cells (RGCs degeneration have been drawing more and more attention. The beneficial effects of nerve growth factor (NGF on the glaucoma have been recently suggested, but its effects on eye tissue are complex and controversial in various studies. Recent clinical trials of systemically and topically administrated NGF demonstrate that NGF is effective in treating several ocular diseases, including glaucoma. NGF has two receptors named high affinity NGF tyrosine kinase receptor TrkA and low affinity receptor p75NTR. Both receptors exist in cells in retina like RGC (expressing TrkA and glia cells (expressing p75NTR. NGF functions by binding to TrkA or p75NTR alone or both together. The binding of NGF to TrkA alone in RGC promotes RGC’s survival and proliferation through activation of TrkA and several prosurvival pathways. In contrast, the binding of NGF to p75NTR leads to apoptosis although it also promotes survival in some cases. Binding of NGF to both TrkA and p75NTR at the same time leads to survival in which p75NTR functions as a TrkA helping receptor. This review discusses the current understanding of the NGF signaling in retina and the therapeutic implications in the treatment of glaucoma.

  3. Analysis and Visualization Tool for Targeted Amplicon Bisulfite Sequencing on Ion Torrent Sequencers.

    Directory of Open Access Journals (Sweden)

    Stephan Pabinger

    Full Text Available Targeted sequencing of PCR amplicons generated from bisulfite deaminated DNA is a flexible, cost-effective way to study methylation of a sample at single CpG resolution and perform subsequent multi-target, multi-sample comparisons. Currently, no platform specific protocol, support, or analysis solution is provided to perform targeted bisulfite sequencing on a Personal Genome Machine (PGM. Here, we present a novel tool, called TABSAT, for analyzing targeted bisulfite sequencing data generated on Ion Torrent sequencers. The workflow starts with raw sequencing data, performs quality assessment, and uses a tailored version of Bismark to map the reads to a reference genome. The pipeline visualizes results as lollipop plots and is able to deduce specific methylation-patterns present in a sample. The obtained profiles are then summarized and compared between samples. In order to assess the performance of the targeted bisulfite sequencing workflow, 48 samples were used to generate 53 different Bisulfite-Sequencing PCR amplicons from each sample, resulting in 2,544 amplicon targets. We obtained a mean coverage of 282X using 1,196,822 aligned reads. Next, we compared the sequencing results of these targets to the methylation level of the corresponding sites on an Illumina 450k methylation chip. The calculated average Pearson correlation coefficient of 0.91 confirms the sequencing results with one of the industry-leading CpG methylation platforms and shows that targeted amplicon bisulfite sequencing provides an accurate and cost-efficient method for DNA methylation studies, e.g., to provide platform-independent confirmation of Illumina Infinium 450k methylation data. TABSAT offers a novel way to analyze data generated by Ion Torrent instruments and can also be used with data from the Illumina MiSeq platform. It can be easily accessed via the Platomics platform, which offers a web-based graphical user interface along with sample and parameter storage

  4. Identification of the Transformational Properties and Transcriptional Targets of the Oncogenic SRY Transcription Factor SOX4

    Science.gov (United States)

    2010-01-01

    lobes of the prostate, seminal vesicles and a few other urogenital tract epithelial cells (15). We initially obtained SOX4fl/+ heterozygote mice and... urogenital organs, including the prostate, bladder, seminal vesicles and testis, as well as control organs such as the liver and thymus were dissected...EGFR and ERBB2 enhancers, we performed ChIP analysis on RWPE-1 prostate cancer cells stably infected with FLAG-SOX4 or a control lentiviral vector. DNA

  5. Microinvasion of liver metastases from colorectal cancer: predictive factors and application for determining clinical target volume

    International Nuclear Information System (INIS)

    Qian, Yang; Zeng, Zhao-Chong; Ji, Yuan; Xiao, Yin-Ping

    2015-01-01

    This study evaluates the microscopic characteristics of liver metastases from colorectal cancer (LMCRC) invasion and provides a reference for expansion from gross tumor volume (GTV) to clinical targeting volume (CTV). Data from 129 LMCRC patients treated by surgical resection at our hospital between January 2008 and September 2009 were collected for study. Tissue sections used for pathology and clinical data were reviewed. Patient information used for the study included gender, age, original tumor site, number of tumors, tumor size, levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 199 (CA199), synchronous or metachronous liver metastases, and whether patients received chemotherapy. The distance of liver microinvasion from the tumor boundary was measured microscopically by two senior pathologists. Of 129 patients evaluated, 81 (62.8 %) presented microinvasion distances from the tumor boundary ranging between 1.0 − 7.0 mm. A GTV-to-CTV expansion of 5, 6.7, or 7.0 mm was required to provide a 95, 99, or 100 % probability, respectively, of obtaining clear resection margins by microscopic observation. The extent of invasion was not related to gender, age, synchronous or metachronous liver metastases, tumor size, CA199 level, or chemotherapy. The extent of invasion was related to original tumor site, CEA level, and number of tumors. A scoring system was established based on the latter three positive predictors. Using this system, an invasion distance less than 3 mm was measured in 93.4 % of patients with a score of ≤1 point, but in only 85.7 % of patients with a score of ≤2 points. The extent of tumor invasion in our LMCRC patient cohort correlated with original tumor site, CEA level, and number of tumors. These positive predictors may potentially be used as a scoring system for determining GTV-to-CTV expansion

  6. Targeting modifiable risk factors in age-related macular degeneration in optometric practice in Sweden

    Directory of Open Access Journals (Sweden)

    Martin L

    2017-04-01

    patients. Targeted education and implementation strategies may be needed. Keywords: age-related macular degeneration, diet, smoking, nutritional supplements

  7. Critical analysis of risk factors for shoulder dystocia.

    Science.gov (United States)

    Tsur, Avishai; Sergienko, Ruslan; Wiznitzer, Arnon; Zlotnik, Alexander; Sheiner, Eyal

    2012-05-01

    The study was aimed to define trends, risk factors and perinatal outcome associated with shoulder dystocia (SD). A population-based study comparing all singleton deliveries with and without SD was conducted. Statistical analysis was performed using multiple logistic regression analysis. Shoulder dystocia complicated 0.2% (n = 451) of all deliveries included in the study (n = 240,189). The rate of SD declined from 0.4% in 1988 to 0.13% in 2009. Independent risk factors for SD in a multivariable analysis were fetal macrosomia (birth-weight ≥ 4 kg; OR = 16.1; 95% CI 13.2-19.6, P Shoulder dystocia, associated with macrosomia, labor dystocia, diabetes mellitus, and advanced maternal age, is an independent risk factor for perinatal mortality. In an era of increased rate of cesarean deliveries, and perhaps increased accuracy of birth weight estimation, the rate of shoulder dystocia gradually declines.

  8. An SPSS R-Menu for Ordinal Factor Analysis

    OpenAIRE

    Basto, Mário; Pereira, José Manuel

    2012-01-01

    Exploratory factor analysis is a widely used statistical technique in the social sciences. It attempts to identify underlying factors that explain the pattern of correlations within a set of observed variables. A statistical software package is needed to perform the calculations. However, there are some limitations with popular statistical software packages, like SPSS. The R programming language is a free software package for statistical and graphical computing. It offers many packages writte...

  9. The Acetyltransferase p300/CBP-Associated Factor Is a p53 Target Gene in Breast Tumor Cells

    Directory of Open Access Journals (Sweden)

    George S. Watts

    2004-05-01

    Full Text Available p300/CBP-associated factor (PCAF is a coactivator of the tumor suppressor, p53. PCAF participates in p53's transactivation of target genes through acetylation of both bound p53 and histones within p53 target promoters. Using microarrays, we discovered that PCAF itself is induced by p53 in a panel of breast tumor cell lines. Two p53 mutant breast tumor cell lines, BT-549 and UACC-1179, were chosen for further study of PCAF induction by wild-type p53. PCAF induction following adenoviral transduction of p53 expression was confirmed with real-time polymerase chain reaction in a time course experiment. Chromatin immunoprecipitation experiments then showed that PCAF induction was associated with increased p53 binding to the PCAF promoter, which contains p53 consensus-binding sites. PCAF induction by p53 activity was further demonstrated in wild-type p53 MCF10A cells when PCAF expression was induced following activation of endogenous wild-type p53 with doxorubicin in a dose- and time-dependent manner. Furthermore, the doxorubicin-induced increase in PCAF expression was blocked by pretreatment of the MCF10A cells with siRNA (small interfering RNA targeted against p53 mRNA. Taken together, the results show that PCAF expression can be induced by wild-type p53.

  10. Identification of MALT1 as both a prognostic factor and a potential therapeutic target of regorafenib in cholangiocarcinoma patients.

    Science.gov (United States)

    Yeh, Chun-Nan; Chang, Yu-Chan; Su, Yeu; Shin-Shian Hsu, Dennis; Cheng, Chi-Tung; Wu, Ren-Chin; Chung, Yi-Hsiu; Chiang, Kun-Chun; Yeh, Ta-Sen; Lu, Meng-Lun; Liu, Chun-Yu; Mu-Hsin Chang, Peter; Chen, Ming-Han; Huang, Chi-Ying F; Hsiao, Michael; Chen, Ming-Huang

    2017-12-26

    Intrahepatic cholangiocarcinoma (CCA) is an aggressive cancer that lacks an effective targeted therapy. Here, we assessed the therapeutic efficacy of regorafenib in CCA, as well as elucidated its underlying mechanism. We first demonstrated that regorafenib not only inhibited growth but also induced apoptosis in human CCA cells. Subsequently, we used in silico approaches to identify MALT1 (Mucosa-associated lymphoid tissue protein 1), which plays an important role in activating NF-κB, as a potential target of regorafenib. Overexpression of Elk-1, but not Ets-1, in HuCCT1 cells markedly reduced their sensitivity to regorafenib, which might be attributed to a significant increase in MALT1 levels. Our results further demonstrated that this drug drastically inhibited MALT1 expression by suppressing the Raf/Erk/Elk-1 pathway. The efficacy of regorafenib in decreasing in vivo CCA growth was confirmed in animal models. Regorafenib efficacy was observed in two MALT1-positive CCA patients who failed to respond to several other lines of therapy. Finally, MALT1 was also identified as an independent poor prognostic factor for patients with intrahepatic CCA. In conclusion, our study identified MALT1 to be a downstream mediator of the Raf/Erk/Elk-1 pathway and suggested that MALT1 may be a new therapeutic target for successful treatment of CCA by regorafenib.

  11. Variation in Veteran Identity as a Factor in Veteran-Targeted Interventions.

    Science.gov (United States)

    Hack, Samantha M; DeForge, Bruce R; Lucksted, Alicia

    2017-07-01

    The sociocultural identities that people self-assign or accept influence their interpersonal interactions and decision making. Identity-based interventions attempt to influence individuals by associating healthy behaviors with in-group membership. Outreach and educational efforts aimed at veterans may rely on "typical" veteran identity stereotypes. However, as discussed in this Open Forum, there is evidence that veteran identity is not monolithic but rather fluctuates on the basis of personal characteristics and individual military service experiences. Overall, the impact of veteran identity on veterans' health behaviors and use of health care is not known and has been understudied. A major limiting factor is the lack of a standardized measure of veteran identity that can assess variations in salience, prominence, and emotional valence.

  12. The E2F transcription factor is a cellular target for the RB protein.

    Science.gov (United States)

    Chellappan, S P; Hiebert, S; Mudryj, M; Horowitz, J M; Nevins, J R

    1991-06-14

    Although it is generally believed that the product of the retinoblastoma susceptibility gene (RB1) is an important regulator of cell proliferation, the biochemical mechanism for its action is unclear. We now show that the RB protein is found in a complex with the E2F transcription factor and that only the under phosphorylated form of RB is in the E2F complex. Moreover, the adenovirus E1A protein can dissociate the E2F-RB complex, dependent on E1A sequence also critical for E1A to bind to RB. These sequences are also critical for E1A to immortalize primary cell cultures and to transform in conjunction with other oncogenes. Taken together, these results suggest that the interaction of RB with E2F is an important event in the control of cellular proliferation and that the dissociation of the complex is part of the mechanism by which E1A inactivates RB function.

  13. The Tumor Necrosis Factor Superfamily of Cytokines in the Inflammatory Myopathies: Potential Targets for Therapy

    Directory of Open Access Journals (Sweden)

    Boel De Paepe

    2012-01-01

    Full Text Available The idiopathic inflammatory myopathies (IM represent a heterogeneous group of autoimmune diseases, of which dermatomyositis (DM, polymyositis (PM, and sporadic inclusion body myositis (IBM are the most common. The crucial role played by tumor necrosis factor alpha (TNFα in the IM has long been recognized. However, so far, 18 other members of the TNF superfamily have been characterized, and many of these have not yet received the attention they deserve. In this paper, we summarize current findings for all TNF cytokines in IM, pinpointing what we know already and where current knowledge fails. For each TNF family member, possibilities for treating inflammatory diseases in general and the IM in particular are explored.

  14. Treatment of gummy smile: Nasal septum dysplasia as etiologic factor and therapeutic target.

    Science.gov (United States)

    Wei, Jiao; Herrler, Tanja; Xu, Hua; Li, Qingfeng; Dai, Chuanchang

    2015-10-01

    Various techniques to improve gummy smile exist. Depending on the individual etiology, previous approaches have focused on osseous, dental, and soft-tissue aspects. On the basis of the identification of nasal septum dysplasia as etiologic factor of gummy smile, we propose a novel strategy for the improvement in the treatment of excessive gingival exposure. In this prospective controlled study, 121 Asian patients with gummy smile and 150 volunteers were examined and compared with regard to the developmental status of the nasal septal cartilage reflected by the columella upward maximum movability (CUMM) as objective measurement parameter. A total of 46 patients with significantly increased CUMM underwent surgical treatment for excessive gingival exposure by septum cartilage reinforcement and, where required, additional extension using an autologous cartilage graft or an expanded polytetrafluoroethylene (ePTFE) implant. Gingival exposure at the fullest smile was photographed, measured, and analyzed before and 1, 3, and 6 months after surgery, and all possible complications were recorded. The results were evaluated in a patient satisfaction survey. CUMM showed a significant statistical difference between the patients desiring treatment for gummy smile (5.6 ± 0.92 mm) and volunteers (3.1 ± 0.76 mm), (p gummy smile, the measured maximum gingival exposure at the fullest smile was 4.52 ± 1.7 mm preoperatively and significantly decreased to 1.79 ± 0.26 mm at 6 months postoperatively (p smile, implant deformation, and acute infection. The postoperative results were highly satisfactory in terms of aesthetic smile. This study proposes a novel strategy of reinforcement and extension of the nasal septum cartilage for the improvement of gummy smile confirming septal cartilage dysplasia as the etiologic factor. Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  15. The transcription factor Prep1 controls hepatic insulin sensitivity and gluconeogenesis by targeting nuclear localization of FOXO1.

    Science.gov (United States)

    Kulebyakin, Konstantin; Penkov, Dmitry; Blasi, Francesco; Akopyan, Zhanna; Tkachuk, Vsevolod

    2016-12-02

    Liver plays a key role in controlling body carbohydrate homeostasis by switching between accumulation and production of glucose and this way maintaining constant level of glucose in blood. Increased blood glucose level triggers release of insulin from pancreatic β-cells. Insulin represses hepatic glucose production and increases glucose accumulation. Insulin resistance is the main cause of type 2 diabetes and hyperglycemia. Currently thiazolidinediones (TZDs) targeting transcriptional factor PPARγ are used as insulin sensitizers for treating patients with type 2 diabetes. However, TZDs are reported to be associated with cardiovascular and liver problems and stimulate obesity. Thus, it is necessary to search new approaches to improve insulin sensitivity. A promising candidate is transcriptional factor Prep1, as it was shown earlier it could affect insulin sensitivity in variety of insulin-sensitive tissues. The aim of the present study was to evaluate a possible involvement of transcriptional factor Prep1 in control of hepatic glucose accumulation and production. We created mice with liver-specific Prep1 knockout and discovered that hepatocytes derived from these mice are much more sensitive to insulin, comparing to their WT littermates. Incubation of these cells with 100 nM insulin results in almost complete inhibition of gluconeogenesis, while in WT cells this repression is only partial. However, Prep1 doesn't affect gluconeogenesis in the absence of insulin. Also, we observed that nuclear content of gluconeogenic transcription factor FOXO1 was greatly reduced in Prep1 knockout hepatocytes. These findings suggest that Prep1 may control hepatic insulin sensitivity by targeting FOXO1 nuclear stability. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. A novel graphical technique for Pinch Analysis applications: Energy Targets and grassroots design

    International Nuclear Information System (INIS)

    Gadalla, Mamdouh A.

    2015-01-01

    Graphical abstract: A new HEN graphical design. - Highlights: • A new graphical technique for heat exchanger networks design. • Pinch Analysis principles and design rules are better interpreted. • Graphical guidelines for optimum heat integration. • New temperature-based graphs provide user-interactive features. - Abstract: Pinch Analysis is for decades a leading tool to energy integration for retrofit and design. This paper presents a new graphical technique, based on Pinch Analysis, for the grassroots design of heat exchanger networks. In the new graph, the temperatures of hot streams are plotted versus those of the cold streams. The temperature–temperature based graph is constructed to include temperatures of hot and cold streams as straight lines, horizontal lines for hot streams, and vertical lines for cold streams. The graph is applied to determine the pinch temperatures and Energy Targets. It is then used to synthesise graphically a complete exchanger network, achieving the Energy Targets. Within the new graph, exchangers are represented by inclined straight lines, whose slopes are proportional to the ratio of heat capacities and flows. Pinch Analysis principles for design are easily interpreted using this new graphical technique to design a complete exchanger network. Network designs achieved by the new technique can guarantee maximum heat recovery. The new technique can also be employed to simulate basic designs of heat exchanger networks. The strengths of the new tool are that it is simply applied using computers, requires no commercial software, and can be used for academic purposes/engineering education

  17. Towards 90-90-90 Target: Factors Influencing Availability, Access, and Utilization of HIV Services—A Qualitative Study in 19 Ugandan Districts

    Directory of Open Access Journals (Sweden)

    Francis Bajunirwe

    2018-01-01

    Full Text Available Background. UNAIDS has set a new target 90-90-90 by 2020. To achieve this target, current programs need to address challenges that limit access, availability, and utilization of HIV testing and treatment services. Therefore, the aim of this study was to identify the barriers that influence access, availability, and utilization of HIV services in rural Uganda within the setting of a large donor funded program. Methods. We conducted key informant interviews with stakeholders at the district level, staff of existing HIV/AIDS projects, and health facilities in 19 districts. Data were also collected from focus group discussions comprised of clients presenting for HIV care and treatment. Data were transcribed and analyzed using content analysis. Results. Barriers identified were as follows: (1 drug shortages including antiretroviral drugs at health facilities. Some patients were afraid to start ART because of worrying about shortages; (2 distance and (3 staffing shortages; (4 stigma persistence; (5 lack of social and economic support initiatives that enhance retention in treatment. Conclusions. In conclusion, our study has identified several factors that influence access, availability, and utilization of HIV services. Programs need to address drug and staff shortages, HIV stigma, and long distances to health facilities to broaden access and utilization in order to realize the UNAIDS target.

  18. Impact of metabolic, hemodynamic and inflammatory factors on target organ damage in healthy subjects

    DEFF Research Database (Denmark)

    Blicher, M.; Kruger, R.; Olesen, Thomas Bastholm

    2015-01-01

    SBP) and diastolic blood pressure (24hDBP), left ventricular mass index (LVMI) by M-mode echocardiography, carotid plaques (CP) by carotid ultra sound and carotid-femoral pulse wave velocity (PWV). To establish best model for association of LVMI, CP, PWV and UACR we used multiple linear regression analysis starting...... with inclusion of all variables without co-linearity taking away one by one non-significant variables. Results: Cardiac hypertrophy assessed by LVMI was primarily associated with gender (beta = 0.37), 24hSBP (beta = 0.26) and HR (beta = -0.15). Insulin resistance (IR) and inflammation only had minor albeit...

  19. Factor analysis of the contextual fine motor questionnaire in children.

    Science.gov (United States)

    Lin, Chin-Kai; Meng, Ling-Fu; Yu, Ya-Wen; Chen, Che-Kuo; Li, Kuan-Hua

    2014-02-01

    Most studies treat fine motor as one subscale in a developmental test, hence, further factor analysis of fine motor has not been conducted. In fact, fine motor has been treated as a multi-dimensional domain from both clinical and theoretical perspectives, and therefore to know its factors would be valuable. The aim of this study is to analyze the internal consistency and factor validity of the Contextual Fine Motor Questionnaire (CFMQ). Based on the ecological observation and literature, the Contextual Fine Motor Questionnaire (CFMQ) was developed and includes 5 subscales: Pen Control, Tool Use During Handicraft Activities, the Use of Dining Utensils, Connecting and Separating during Dressing and Undressing, and Opening Containers. The main purpose of this study is to establish the factorial validity of the CFMQ through conducting this factor analysis study. Among 1208 questionnaires, 904 were successfully completed. Data from the children's CFMQ submitted by primary care providers was analyzed, including 485 females (53.6%) and 419 males (46.4%) from grades 1 to 5, ranging in age from 82 to 167 months (M=113.9, SD=16.3). Cronbach's alpha was used to measure internal consistency and explorative factor analysis was applied to test the five factor structures within the CFMQ. Results showed that Cronbach's alpha coefficient of the CFMQ for 5 subscales ranged from .77 to .92 and all item-total correlations with corresponding subscales were larger than .4 except one item. The factor loading of almost all items classified to their factor was larger than .5 except 3 items. There were five factors, explaining a total of 62.59% variance for the CFMQ. In conclusion, the remaining 24 items in the 5 subscales of the CFMQ had appropriate internal consistency, test-retest reliability and construct validity. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Md-miR156ab and Md-miR395 Target WRKY Transcription Factors to Influence Apple Resistance to Leaf Spot Disease.

    Science.gov (United States)

    Zhang, Qiulei; Li, Yang; Zhang, Yi; Wu, Chuanbao; Wang, Shengnan; Hao, Li; Wang, Shengyuan; Li, Tianzhong

    2017-01-01

    MicroRNAs (miRNAs) are key regulators of gene expression that post-transcriptionally regulate transcription factors involved in plant physiological activities. Little is known about the effects of miRNAs in disease resistance in apple ( Malus × domestica ). We globally profiled miRNAs in the apple cultivar Golden Delicious (GD) infected or not with the apple leaf spot fungus Alternaria alternaria f. sp. mali (ALT1), and identified 58 miRNAs that exhibited more than a 2-fold upregulation upon ALT1 infection. We identified a pair of miRNAs that target protein-coding genes involved in the defense response against fungal pathogens; Md-miR156ab targets a novel WRKY transcription factor, MdWRKYN1, which harbors a TIR and a WRKY domain. Md-miR395 targets another transcription factor, MdWRKY26, which contains two WRKY domains. Real-time PCR analysis showed that Md-miR156ab and Md-miR395 levels increased, while MdWRKYN1 and MdWRKY26 expression decreased in ALT1-inoculated GD leaves; furthermore, the overexpression of Md-miR156ab and Md-miR395 resulted in a significant reduction in MdWRKYN1 and MdWRKY26 expression. To investigate whether these miRNAs and their targets play a crucial role in plant defense, we overexpressed MdWRKYN1 or knocked down Md-miR156ab activity, which in both cases enhanced the disease resistance of the plants by upregulating the expression of the WRKY-regulated pathogenesis-related (PR) protein-encoding genes MdPR3-1, MdPR3-2, MdPR4, MdPR5, MdPR10-1 , and MdPR10-2 . In a similar analysis, we overexpressed MdWRKY26 or suppressed Md-miR395 activity, and found that many PR protein-encoding genes were also regulated by MdWRKY26 . In GD, ALT-induced Md-miR156ab and Md-miR395 suppress MdWRKYN1 and MdWRKY26 expression, thereby decreasing the expression of some PR genes, and resulting in susceptibility to ALT1.